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Zhao X, Ren Z, Li W, Liu Q, Dong Y, Huang Y. Alterations in ocular fungal microbiota in patients with fungal keratitis: a comparative study from coastal regions of Eastern China. BMC Ophthalmol 2025; 25:316. [PMID: 40426143 PMCID: PMC12107729 DOI: 10.1186/s12886-025-04133-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Accepted: 05/13/2025] [Indexed: 05/29/2025] Open
Abstract
OBJECTIVE The understanding of the ocular microbiota, particularly in fungal keratitis (FK), is evolving with advancements in high-throughput sequencing technologies. Traditional culture-based methods may not fully capture the microbial diversity present in keratitis, highlighting the need for more comprehensive approaches to explore microbial dysbiosis in corneal infections. This study aimed to reveal the dysbacteriosis of the ocular fungal microbiome associated with FK. METHODS We analysed 105 samples, including conjunctival swabs from healthy eyes (HE) and conjunctival swabs (SW), as well as corneal scrapings (SC), from FK eyes. Positive results were observed in 58 samples, and detailed taxonomic categorization was carried out across multiple levels-phylum, class, order, family, and genus-using high-throughput ITS sequencing. Alpha and beta diversity indices were computed, and interaction networks at the genus level were predicted to elucidate changes in microbial communities. The analyses also included assessments of functional groups within the fungal microbiome. RESULTS Among the samples, the HE, SW, and SC groups presented differences in positivity rates and diversity indices. Compared with HE eyes, infected eyes (SW and SC) presented significantly greater Good's coverage estimator and lower Chao1, Shannon, and Simpson diversity indices, indicating reduced species richness and evenness. At multiple taxonomic levels, various taxa were significantly downregulated in the FK eyes. Functional analyses revealed differences, notably, an increase in the number of litter saprotrophs in FK eyes. Ascomycota and Basidiomycota were identified as core phyla in the ocular microbiota interaction network. CONCLUSION Fungal keratitis significantly alters the ocular surface microbiome, which is characterized by decreased microbial richness and evenness. High-throughput sequencing revealed a complex interaction network with significant variability between healthy and infected eyes. Additionally, these findings suggest potential benefits from early and aggressive debridement in managing FK due to its impact on functional microbial groups.
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Affiliation(s)
- Xudong Zhao
- State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, School of Ophthalmology, Shandong Eye Institute, Shandong First Medical University, Qingdao, 266071, Shandong Provence, China
| | - Zhichao Ren
- Qingdao University, Qingdao Medical College, Qingdao, 266071, Shandong Provence, China
| | - Wenfeng Li
- Department of Medical Oncology, the Affiliated Hospital of Qingdao University, Qingdao, 266071, Shandong Provence, China
| | - Qing Liu
- State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, School of Ophthalmology, Shandong Eye Institute, Shandong First Medical University, Qingdao, 266071, Shandong Provence, China
| | - Yanling Dong
- State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, School of Ophthalmology, Shandong Eye Institute, Shandong First Medical University, Qingdao, 266071, Shandong Provence, China
| | - Yusen Huang
- State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, School of Ophthalmology, Shandong Eye Institute, Shandong First Medical University, Qingdao, 266071, Shandong Provence, China.
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Jiang B, An Z, Niu L, Qin D. Precise genome editing process and its applications in plants driven by AI. Funct Integr Genomics 2025; 25:109. [PMID: 40413357 DOI: 10.1007/s10142-025-01619-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2025] [Revised: 05/12/2025] [Accepted: 05/15/2025] [Indexed: 05/27/2025]
Abstract
Genome editing technologies have emerged as the keystone of biotechnological research, enabling precise gene modification. The field has evolved rapidly through revolutionary advancements, transitioning from early explorations to the breakthrough of the CRISPR-Cas system. The emergence of the CRISPR-Cas system represents a huge leap in genome editing, prompting the development of advanced tools such as base and prime editors, thereby enhancing precise genomic engineering capabilities. The rapid integration of AI across disciplines is now driving another transformative phase in genome editing, streamlining workflows and enhancing precision. The application prospects of genome editing technology are extensive, particularly in plant breeding, where it has already presented unparalleled opportunities for improving plant traits. Here, we review early genome editing technologies, including meganucleases, ZFNs, TALENs, and CRISPR-Cas systems. We also provide a detailed introduction to next-generation editing tools-such as base editors and prime editors-and their latest applications in plants. At the same time, we summarize and prospect the cutting-edge developments and future trends of genome editing technologies in combination with the rapidly rising AI technology, including optimizing editing systems, predicting the efficiency of editing sites and designing editing strategies. We are convinced that as these technologies progress and their utilization expands, they will provide pioneering solutions to global challenges, ushering in an era of health, prosperity, and sustainability.
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Affiliation(s)
- Bo Jiang
- State Key Laboratory of Tree Genetics and Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083, China
- National Engineering Research Center of Tree Breeding and Ecological Restoration, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083, China
- Key Laboratory of Genetics and Breeding in Forest Trees and Ornamental Plants, MOE, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083, China
| | - Zeyu An
- University of Science and Technology Beijing, Beijing, 100083, China
| | - Linlin Niu
- State Key Laboratory of Tree Genetics and Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083, China
- National Engineering Research Center of Tree Breeding and Ecological Restoration, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083, China
- Key Laboratory of Genetics and Breeding in Forest Trees and Ornamental Plants, MOE, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083, China
| | - Debin Qin
- State Key Laboratory of Tree Genetics and Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083, China.
- National Engineering Research Center of Tree Breeding and Ecological Restoration, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083, China.
- Key Laboratory of Genetics and Breeding in Forest Trees and Ornamental Plants, MOE, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083, China.
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Huang CW, Zhang WZ, Liao Y, Hu T, Li JM, Wang CL. A targeted approach: Gene and RNA editing for neurodegenerative disease treatment. Life Sci 2025; 376:123756. [PMID: 40412606 DOI: 10.1016/j.lfs.2025.123756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 05/15/2025] [Accepted: 05/21/2025] [Indexed: 05/27/2025]
Abstract
With the global aging trend, neurodegenerative diseases (NDs) have emerged as a significant public health concern in the 21st century, imposing substantial economic burdens on families and society. NDs are characterized by cognitive and motor decline, resulting from a combination of genetic and environmental factors. Currently, there is no cure for NDs. Gene and RNA editing therapies offer new possibilities for addressing NDs. Gene editing involves modifying mutant genes associated with NDs, while RNA editing can directly modify RNA molecules to regulate the protein translation process, potentially influencing the expression of genes related to NDs. In this review, we examined the historical evolution, mechanisms of action, applications in NDs, advantages and disadvantages, as well as ethical and safety considerations of gene and RNA editing. While gene and RNA editing technologies hold promise for treating NDs, further research and development are needed to address safety, efficacy, and treatment timing issues, ultimately offering improved treatment options for ND patients. Our review provides valuable insights for future gene and RNA editing applications in ND treatment.
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Affiliation(s)
- Chen-Wei Huang
- Department of Stress Medicine, Faculty of Psychology, Naval Medical University, Shanghai, 200433, China
| | - Wang-Zheqi Zhang
- Department of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai 200433, China; School of Anesthesiology, Naval Medical University, Shanghai 200433, China
| | - Yan Liao
- Department of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai 200433, China; School of Anesthesiology, Naval Medical University, Shanghai 200433, China
| | - Ting Hu
- Department of Stress Medicine, Faculty of Psychology, Naval Medical University, Shanghai, 200433, China
| | - Jia-Mei Li
- Department of Neurology, The 971st Hospital of Navy, Qingdao 266071, China.
| | - Chang-Li Wang
- Department of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai 200433, China.
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Yang J, He M, Li Y, Guo Y, Chen T, Zuo Y. Enhancing remediation of As-contaminated orchard soil through intercropping Pteris vittata with low-accumulating peach trees. ENVIRONMENTAL GEOCHEMISTRY AND HEALTH 2025; 47:187. [PMID: 40293581 DOI: 10.1007/s10653-025-02490-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 03/30/2025] [Indexed: 04/30/2025]
Abstract
In recent years, the frequent occurrence of heavy metal contamination in orchard soils has posed a threat to the quality and edible safety of fruits. To investigate the remediation efficiency and explore the application potential of intercropping patterns featuring hyperaccumulator Pteris vittata in orchards, this study focused on peach trees, a major economic fruit crop, and conducted a systematic examination of intercropping in As-contaminated orchard soil. First, the screening pot experiment compared the As accumulation ability of 10 main peach cultivars in local areas. The results showed that the As content in the peach roots was the highest, followed by the leaves and stems. Lvhua 9 (LH9) and Ruipan 13 (RP13) peach trees had better growth and lower As accumulation. Second, a pot intercropping experiment of P. vittata and low-As peach cultivars (LH9 and RP13) was conducted by the rhizosphere bag method (monoculture, restricted intercropping, opening intercropping). Compared with monoculture, intercropping increased the As content in P. vittata (8.29-134%) and decreased the As content in peach (31.1-69.1%) by root interaction. In addition, intercropping significantly increased the abundance of As-resistant Sphingomonas in the rhizospheres of the two peach cultivars and P. vittata (21.4% to 108%), and the As removal rate was increased (up to 198%). Finally, in the field experiment, the intercropping of P. vittata and LH9 significantly promoted the growth, photosynthesis, and As uptake of P. vittata, especially in rainy July and August. Moreover, the yield of peach fruits was not notably affected, and their As content met national standards. In conclusion, intercropping P. vittata with selected peach cultivars in As-contaminated orchard soils effectively enhances As remediation efficiency while maintaining fruit quality and safety, demonstrating its promising application potential for sustainable orchard management.
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Affiliation(s)
- Junxing Yang
- Center for Environmental Remediation, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China
- University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China
| | - Mengke He
- Center for Environmental Remediation, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China
- University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China
| | - Yufeng Li
- Center for Environmental Remediation, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
- University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
- Institute of Quality Standard and Testing Technology, Beijing Academy of Agriculture and Forestry Sciences, Beijing, 100097, People's Republic of China.
| | - Yule Guo
- Center for Environmental Remediation, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China
- University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China
| | - Tongbin Chen
- Center for Environmental Remediation, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China
- University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China
| | - Yiping Zuo
- China Green Enterprise Limited, Beijing, 100035, People's Republic of China
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Mohanta R, Maiti P, Sharangi AB, Roy S, Hazra S, Chakraborty S, Ghorai S. Directed mutagenesis in fruit crops. 3 Biotech 2025; 15:104. [PMID: 40177007 PMCID: PMC11958931 DOI: 10.1007/s13205-025-04268-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Accepted: 03/07/2025] [Indexed: 04/05/2025] Open
Abstract
Fruit crops are rich source of important vitamins, minerals, and dietary fibres. They are essential for global agriculture with respect to nutritional security. Globally, there is a rapid decline in the genetic base of fruit crops warranting breeding strategies to overcome the challenge. Applied mutagenesis has emerged as a viable approach for the focused enhancement of fruit crops utilizing precise genetic alterations to increase a variety of desirable characteristics. However, traditional mutagenesis using physical and chemical mutagens are majorly random in nature. Directed mutagenesis with advancements in genetic engineering and molecular technology allows precise manipulation of genes, which facilitates the efficient and precise knockout of target genes and the targeted insertion or modification of specific DNA sequences within the genome via homologous recombination (HR)-mediated gene replacement. This review presents an in-depth exploration of several directed mutagenesis techniques including CRISPR-Cas9, TILLING, TALEN, MutMap, and MutMap + emphasizing their transformative applications in fruit crops. It also discusses about space mutagenesis. These advanced techniques empower researchers to precisely introduce specific mutations into the genome, skilfully altering gene expression and reshaping protein function with remarkable precision. This review highlights successful examples of directed mutagenesis in a variety of fruit crops such as apples, grapes, citrus, and strawberries and elucidates the impact of directed mutagenesis on traits such as fruit size, colour, flavour, shelf-life, and resistance to diseases and environmental stresses.
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Affiliation(s)
- Rajdeep Mohanta
- Department of Agriculture, Brainware University, Barasat, Kolkata, 700125 West Bengal India
| | - Payal Maiti
- Department of Post-Harvest Management, Bidhan Chandra Krishi Viswavidyalaya, Mohanpur, 741252 West Bengal India
| | - Amit Baran Sharangi
- Department of Plantation Spices Medicinal & Aromatic Crops, Bidhan Chandra Krishi Viswavidyalaya, Mohanpur, 741252 West Bengal India
| | - Sourav Roy
- Department of Agriculture, Brainware University, Barasat, Kolkata, 700125 West Bengal India
| | - Soham Hazra
- Department of Agriculture, Brainware University, Barasat, Kolkata, 700125 West Bengal India
| | - Souvik Chakraborty
- Department of Post-Harvest Management, Bidhan Chandra Krishi Viswavidyalaya, Mohanpur, 741252 West Bengal India
| | - Subhadwip Ghorai
- Department of Agriculture, Brainware University, Barasat, Kolkata, 700125 West Bengal India
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Ji M, Xiong K, Fu D, Chi Y, Wang Y, Yao L, Yang X, Yan Y, Zhu H, Li Y, Ren B, Zou L. The landscape of the microbiome at different stages of root caries. Clin Oral Investig 2025; 29:217. [PMID: 40155488 DOI: 10.1007/s00784-025-06301-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Accepted: 03/25/2025] [Indexed: 04/01/2025]
Abstract
OBJECTIVE To investigate the relationship between microorganisms and root caries, identify core species, and explore their interactions. MATERIALS AND METHODS Thirty patients with different levels of root caries were included. Plaques from superficial (n = 30) and deep root caries (n = 30) and sound root surfaces (n = 30) were collected. Microbial diversity and composition across different stages of root caries were analyzed using 16 S rRNA and 18 S rRNA high-throughput sequencing. Wilcoxon paired comparisons were conducted to minimize individual variations. LefSe analysis was performed to identify stage-specific microbial enrichment. In vitro biofilm models of C. albicans, S. mutans and A. viscosus were established to examine the effects of C. albicans on biofilm formation, virulence factor expression, and metabolic pathway regulation. Fungal transcriptomes were sequenced to explore how fungal species affect bacterial growth and cariogenicity. RESULTS No significant differences in microbial diversity or structure were observed, but relative abundances of some species differed significantly (p < 0.05). LefSe analysis showed that the genus Streptococcus, Actinomyces, Lactobacillus, and Bacillus were enriched in superficial caries, whereas Prevotella was enriched in deep lesions. C. albicans was the predominant fungal species in root plaques and positively correlated with S. mutans and Actinomyces sp. HMT448. C. albicans promoted the growth, biofilm formation, and cariogenicity of S. mutans and A. viscosus via the arginine biosynthesis pathway. CONCLUSION Oral microecology is stable, and species imbalance is a key factor in root caries. Cross-kingdom interactions between S. mutans, A. viscosus, and C. albicans enhance cariogenic biofilms via the arginine biosynthesis pathway, offering insights for clinical treatments of root caries. CLINICAL RELEVANCE Our study revealed the first landscape of the microbiome from different stages of root caries and indicated that targeting the interactions of core species may be a practical way to prevent and treat clinical root caries.
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Affiliation(s)
- Mengzhen Ji
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Kaixin Xiong
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Di Fu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Yaqi Chi
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Ye Wang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Lin Yao
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Xueqin Yang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Yujia Yan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Hualing Zhu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Yanyao Li
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Biao Ren
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China.
- Tianfu Jiangxi Laboratory, Chengdu, Sichuan, China.
| | - Ling Zou
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Conservation Dentistry and Endodontics, West China School of Stomatology, Sichuan University, Chengdu, China.
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Mrisho II, Musazade E, Chen H, Zhao H, Xing J, Li X, Han J, Cai E. Unlocking the Therapeutic Potential of Patchouli Leaves: A Comprehensive Review of Phytochemical and Pharmacological Insights. PLANTS (BASEL, SWITZERLAND) 2025; 14:1034. [PMID: 40219102 PMCID: PMC11990424 DOI: 10.3390/plants14071034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Revised: 03/19/2025] [Accepted: 03/24/2025] [Indexed: 04/14/2025]
Abstract
Plant-based products play an increasingly vital role in the pharmaceutical industry, including Pogostemon cablin (Blanco) Benth. (patchouli), which is notable for its rich history and extensive use in traditional medicine. Patchouli has a longstanding historical use as a remedy for a wide range of health conditions, including colds, fevers, headaches, inflammation, digestive disorders, and insect and snake bites. Comprehensive phytochemical studies have revealed that patchouli leaves contain diverse valuable bioactive compounds, notably patchouli alcohol, β-patchoulene, pogostone, α-bulnesene, and β-caryophyllene. Recent studies have demonstrated that patchouli leaves exhibit various pharmacological properties, including anti-oxidant, anti-inflammatory, antimicrobial, antidepressant, and anticancer effects. Despite robust traditional knowledge, specific therapeutic applications of patchouli leaves require scientific validation and standardization of their bioactive compounds. This review provides a comprehensive overview of the existing literature on the phytochemical composition, pharmacological properties, and underlying mechanisms of action of patchouli essential oil (PEO) and plant extracts obtained from patchouli leaves. It offers detailed insights into potential therapeutic applications, aiming to inform and guide future research across multiple medical disciplines. Ultimately, this review underscores the need for further research to validate and develop the medicinal applications of patchouli leaves, providing a foundation for future healthcare advancements.
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Affiliation(s)
- Isack Ibrahim Mrisho
- College of Chinese Medicinal Material, Jilin Agricultural University, Changchun 130118, China; (I.I.M.); (H.C.); (H.Z.); (J.X.); (X.L.)
| | - Elshan Musazade
- Key Laboratory of Soybean Molecular Design Breeding, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China;
- College of Life Science, Jilin Agricultural University, Changchun 130118, China
| | - Haobo Chen
- College of Chinese Medicinal Material, Jilin Agricultural University, Changchun 130118, China; (I.I.M.); (H.C.); (H.Z.); (J.X.); (X.L.)
| | - Huixuan Zhao
- College of Chinese Medicinal Material, Jilin Agricultural University, Changchun 130118, China; (I.I.M.); (H.C.); (H.Z.); (J.X.); (X.L.)
| | - Junjia Xing
- College of Chinese Medicinal Material, Jilin Agricultural University, Changchun 130118, China; (I.I.M.); (H.C.); (H.Z.); (J.X.); (X.L.)
| | - Xue Li
- College of Chinese Medicinal Material, Jilin Agricultural University, Changchun 130118, China; (I.I.M.); (H.C.); (H.Z.); (J.X.); (X.L.)
| | - Jiahong Han
- College of Chinese Medicinal Material, Jilin Agricultural University, Changchun 130118, China; (I.I.M.); (H.C.); (H.Z.); (J.X.); (X.L.)
| | - Enbo Cai
- College of Chinese Medicinal Material, Jilin Agricultural University, Changchun 130118, China; (I.I.M.); (H.C.); (H.Z.); (J.X.); (X.L.)
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Cao ML, Han RY, Chen SD, Zhao DY, Shi MY, Zou JH, Li L, Jiang HK. Gene Editing: An Effective Tool for the Future Treatment of Kidney Disease. J Inflamm Res 2025; 18:4001-4018. [PMID: 40125088 PMCID: PMC11927957 DOI: 10.2147/jir.s506760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 02/18/2025] [Indexed: 03/25/2025] Open
Abstract
Gene editing technology involves modifying target genes to alter genetic traits and generate new phenotypes. Beginning with zinc-finger nucleases (ZFN) and transcription activator-like effector nucleases (TALEN), the field has evolved through the advent of clustered regularly interspaced short palindromic repeats and CRISPR-associated protein (CRISPR-Cas) systems, and more recently to base editors (BE) and prime editors (PE). These innovations have provided deep insights into the molecular mechanisms of complex biological processes and have paved the way for novel therapeutic strategies for a range of diseases. Gene editing is now being applied in the treatment of both genetic and acquired kidney diseases, as well as in kidney transplantation and the correction of genetic mutations. This review explores the current applications of mainstream gene editing technologies in biology, with a particular emphasis on their roles in kidney disease research and treatment of. It also addresses the limitations and challenges associated with these technologies, while offering perspectives on their future potential in this field.
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Affiliation(s)
- Mei-Ling Cao
- Department of Neonatology, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China
| | - Rui-Yi Han
- Department of Pediatrics, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China
| | - Si-Da Chen
- Department of Orthopaedic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of China
| | - Dan-Yang Zhao
- Department of Pediatrics, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China
| | - Ming-Yue Shi
- Department of Pediatrics, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China
| | - Jia-Hui Zou
- Department of Pediatrics, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China
| | - Lei Li
- Department of Orthopaedic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of China
| | - Hong-Kun Jiang
- Department of Pediatrics, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China
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Dong S, Peng K, Liu Q, Zhang M, Luo Y, Li ZH. Dual role of KHCO₃ priming: reduces seed-borne pathogens on sorghum seeds and promotes seed germination. BMC Microbiol 2025; 25:134. [PMID: 40075265 PMCID: PMC11900088 DOI: 10.1186/s12866-025-03824-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 02/13/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Seed-borne diseases have seriously affected the sustainability of sorghum cultivation in China as the demand for organic products in the winemaking industry has limited the use of chemical fungicides. RESULTS This study conducted a comprehensive analysis of fungal diversity in sorghum seeds from three major growing regions in Guizhou Province. Using a combination of traditional tissue separation and high-throughput sequencing, we identified Colletotrichum, Fusarium, Cladosporium, and Alternaria as dominant fungi. Pathogenicity tests revealed that strains GD202206, GD202219, and GD202242 were pathogenic and were identified as C. sublineola through morphological and multi-locus phylogeny analysis (ITS、CAPDH、ACT、CHS-1 and TUB2). 16 fungicides for seed priming experiments with sorghum seeds, the results indicated that priming with KHCO₃ significantly enhanced germination of the sorghum seeds, with both indoor and outdoor emergence rates notably higher. Analysis of the fungal changes before and after KHCO₃ priming revealed a significant reduction in the abundance of the Colletotrichum genus. Additionally, KHCO₃ altered the community structure of fungi within the sorghum seeds, reducing population richness. Inter-generic relationships were rebalanced, with antagonism decreased and synergy increased following KHCO₃ treatment. Non-target metabolomic analysis indicated that KHCO₃ enhances sorghum seed germination via the phenylalanine and flavonoid pathways and exhibits antifungal properties through the cyanoamino acid metabolic pathway. CONCLUSION This study identified C. sublineola as the primary pathogenic fungus carried by sorghum seeds. KHCO₃ treatment has a dual effect on sorghum seeds: on one hand, it suppresses pathogen transmission by reducing the abundance of the Colletotrichum genus; on the other hand, it promotes germination and seedling emergence, thereby enhancing both germination and emergence rates.
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Affiliation(s)
- Shuai Dong
- College of Agriculture/Institute of Rice Industry Technology Research, Key Laboratory of Plant Resource, Guizhou University, Guiyang, 550025, China
- Key Laboratory of Molecular Breeding for Grain and Oil Crops in Guizhou Province, Guiyang, 550025, China
- Qiannan Academy of Agricultural Sciences, Duyun, 558000, China
- Key Laboratory of Functional Agriculture of Guizhou Provincial Higher Education Institutions, Guiyang, 550025, China
| | - Keqin Peng
- College of Agriculture/Institute of Rice Industry Technology Research, Key Laboratory of Plant Resource, Guizhou University, Guiyang, 550025, China
- Key Laboratory of Molecular Breeding for Grain and Oil Crops in Guizhou Province, Guiyang, 550025, China
- Key Laboratory of Functional Agriculture of Guizhou Provincial Higher Education Institutions, Guiyang, 550025, China
| | - Qiyuan Liu
- College of Agriculture/Institute of Rice Industry Technology Research, Key Laboratory of Plant Resource, Guizhou University, Guiyang, 550025, China
- Key Laboratory of Molecular Breeding for Grain and Oil Crops in Guizhou Province, Guiyang, 550025, China
- Key Laboratory of Functional Agriculture of Guizhou Provincial Higher Education Institutions, Guiyang, 550025, China
| | - Min Zhang
- College of Agriculture/Institute of Rice Industry Technology Research, Key Laboratory of Plant Resource, Guizhou University, Guiyang, 550025, China
- Key Laboratory of Molecular Breeding for Grain and Oil Crops in Guizhou Province, Guiyang, 550025, China
- Key Laboratory of Functional Agriculture of Guizhou Provincial Higher Education Institutions, Guiyang, 550025, China
| | - Yan Luo
- College of Agriculture/Institute of Rice Industry Technology Research, Key Laboratory of Plant Resource, Guizhou University, Guiyang, 550025, China
- Key Laboratory of Molecular Breeding for Grain and Oil Crops in Guizhou Province, Guiyang, 550025, China
- Key Laboratory of Functional Agriculture of Guizhou Provincial Higher Education Institutions, Guiyang, 550025, China
| | - Zhen Hua Li
- College of Agriculture/Institute of Rice Industry Technology Research, Key Laboratory of Plant Resource, Guizhou University, Guiyang, 550025, China.
- Key Laboratory of Molecular Breeding for Grain and Oil Crops in Guizhou Province, Guiyang, 550025, China.
- Key Laboratory of Functional Agriculture of Guizhou Provincial Higher Education Institutions, Guiyang, 550025, China.
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Ragozzino C, Casella V, Coppola A, Scarpato S, Buonocore C, Consiglio A, Palma Esposito F, Galasso C, Tedesco P, Della Sala G, de Pascale D, Vitale L, Coppola D. Last Decade Insights in Exploiting Marine Microorganisms as Sources of New Bioactive Natural Products. Mar Drugs 2025; 23:116. [PMID: 40137302 PMCID: PMC11943599 DOI: 10.3390/md23030116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 02/28/2025] [Accepted: 03/03/2025] [Indexed: 03/27/2025] Open
Abstract
Marine microorganisms have emerged as prolific sources of bioactive natural products, offering a large chemical diversity and a broad spectrum of biological activities. Over the past decade, significant progress has been made in discovering and characterizing these compounds, pushed by technological innovations in genomics, metabolomics, and bioinformatics. Furthermore, innovative isolation and cultivation approaches have improved the isolation of rare and difficult-to-culture marine microbes, leading to the identification of novel secondary metabolites. Advances in synthetic biology and metabolic engineering have further optimized natural product yields and the generation of novel compounds with improved bioactive properties. This review highlights key developments in the exploitation of marine bacteria, fungi, and microalgae for the discovery of novel natural products with potential applications in diverse fields, underscoring the immense potential of marine microorganisms in the growing Blue Economy sector.
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Affiliation(s)
- Costanza Ragozzino
- Department of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via Ammiraglio, Ferdinando Acton 55, 80133 Naples, Italy; (C.R.); (V.C.); (A.C.); (S.S.); (C.B.); (A.C.); (F.P.E.); (P.T.); (G.D.S.); (D.d.P.)
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno d’Alcontres, 31, 98166 Messina, Italy
| | - Vincenza Casella
- Department of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via Ammiraglio, Ferdinando Acton 55, 80133 Naples, Italy; (C.R.); (V.C.); (A.C.); (S.S.); (C.B.); (A.C.); (F.P.E.); (P.T.); (G.D.S.); (D.d.P.)
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno d’Alcontres, 31, 98166 Messina, Italy
| | - Alessandro Coppola
- Department of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via Ammiraglio, Ferdinando Acton 55, 80133 Naples, Italy; (C.R.); (V.C.); (A.C.); (S.S.); (C.B.); (A.C.); (F.P.E.); (P.T.); (G.D.S.); (D.d.P.)
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno d’Alcontres, 31, 98166 Messina, Italy
| | - Silvia Scarpato
- Department of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via Ammiraglio, Ferdinando Acton 55, 80133 Naples, Italy; (C.R.); (V.C.); (A.C.); (S.S.); (C.B.); (A.C.); (F.P.E.); (P.T.); (G.D.S.); (D.d.P.)
| | - Carmine Buonocore
- Department of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via Ammiraglio, Ferdinando Acton 55, 80133 Naples, Italy; (C.R.); (V.C.); (A.C.); (S.S.); (C.B.); (A.C.); (F.P.E.); (P.T.); (G.D.S.); (D.d.P.)
| | - Antonella Consiglio
- Department of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via Ammiraglio, Ferdinando Acton 55, 80133 Naples, Italy; (C.R.); (V.C.); (A.C.); (S.S.); (C.B.); (A.C.); (F.P.E.); (P.T.); (G.D.S.); (D.d.P.)
| | - Fortunato Palma Esposito
- Department of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via Ammiraglio, Ferdinando Acton 55, 80133 Naples, Italy; (C.R.); (V.C.); (A.C.); (S.S.); (C.B.); (A.C.); (F.P.E.); (P.T.); (G.D.S.); (D.d.P.)
| | - Christian Galasso
- Department of Ecosustainable Marine Biotechnology, Calabria Marine Centre, CRIMAC, Stazione Zoologica Anton Dohrn, C. da Torre Spaccata, 87071 Amendolara, Italy;
| | - Pietro Tedesco
- Department of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via Ammiraglio, Ferdinando Acton 55, 80133 Naples, Italy; (C.R.); (V.C.); (A.C.); (S.S.); (C.B.); (A.C.); (F.P.E.); (P.T.); (G.D.S.); (D.d.P.)
| | - Gerardo Della Sala
- Department of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via Ammiraglio, Ferdinando Acton 55, 80133 Naples, Italy; (C.R.); (V.C.); (A.C.); (S.S.); (C.B.); (A.C.); (F.P.E.); (P.T.); (G.D.S.); (D.d.P.)
| | - Donatella de Pascale
- Department of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via Ammiraglio, Ferdinando Acton 55, 80133 Naples, Italy; (C.R.); (V.C.); (A.C.); (S.S.); (C.B.); (A.C.); (F.P.E.); (P.T.); (G.D.S.); (D.d.P.)
| | - Laura Vitale
- Department of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via Ammiraglio, Ferdinando Acton 55, 80133 Naples, Italy; (C.R.); (V.C.); (A.C.); (S.S.); (C.B.); (A.C.); (F.P.E.); (P.T.); (G.D.S.); (D.d.P.)
| | - Daniela Coppola
- Department of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via Ammiraglio, Ferdinando Acton 55, 80133 Naples, Italy; (C.R.); (V.C.); (A.C.); (S.S.); (C.B.); (A.C.); (F.P.E.); (P.T.); (G.D.S.); (D.d.P.)
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Li Z, Chen S, Yin B, Wei J, Wang D, Zhou H, Sun Z. Intermittent fasting regulates gut microbiota and serum metabolome profiles in middle-aged mice fed high-fat diet. Nutr Metab (Lond) 2025; 22:16. [PMID: 40001132 PMCID: PMC11863773 DOI: 10.1186/s12986-025-00904-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 01/27/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Intermittent fasting (IF) has received wide attention as an effective diet strategy. Existing studies showed that IF is a promising approach for weight control, improving insulin sensitivity and reducing type 2 diabetes mellitus (T2DM) prevalence. METHODS Twenty-eight 8-month-old male C57BL/6J mice were randomly divided into a normal control group (NC), a high-fat diet group (HFD) and an HFD + IF group. Body weight (BW) and food intake were monitored weekly. After 20 weeks, the intraperitoneal glucose tolerance test (IPGTT), oral glucose tolerance test (OGTT), and intraperitoneal insulin tolerance test (IPITT) were performed weekly in sequence. Fresh faeces were collected to examine changes in gut microbiota, and serum untargeted metabolite profiling was conducted on serum samples. RESULTS IF significantly reduced weight gain, fat mass and liver weight, improved glucose tolerance and insulin sensitivity in middle-aged mice fed with high-fat diet. 16 S rRNA gene sequencing revealed that IF significantly reduced the Firmicutes/Bacteroidetes (F/B) ratio by increased Muribaculaceae, Bacteroides, Parabacteroides, and decreased Bilophila, Colidextribacter, Oscillibacter. The serum untargeted metabolomics revealed that IF could modulate differential metabolites and metabolic pathways associated with glycolipid metabolism. Spearman's correlation analysis indicated that key differential microbiota were strongly correlated with glucose metabolism-related indicators and serum metabolites such as stearic acid, obeticholic acid, and N-acetylglycine. CONCLUSIONS IF improves glucose metabolism, regulates gut microbiota, and alters serum metabolites in middle-aged mice fed a high-fat diet. This provides a new pathway for trials testing diabetes prevention in middle-aged and elderly patients.
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Affiliation(s)
- Ziru Li
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Sufang Chen
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
| | - Bingbing Yin
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Jiacun Wei
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Duofei Wang
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Huoxiang Zhou
- Laboratory of Microbiology and Immunology, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, China
| | - Zhi Sun
- Department of Pharmacy, Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou Key Laboratory of Clinical Mass Spectrometry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
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Zhao M, Wen J, Chen ISY, Liu J, Lu Y. Excision of HIV-1 Provirus in Human Primary Cells with Nanocapsuled TALEN Proteins. ACS APPLIED BIO MATERIALS 2025; 8:1227-1239. [PMID: 39889258 PMCID: PMC11892523 DOI: 10.1021/acsabm.4c01544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2025]
Abstract
Despite the tremendous success of combination antiretroviral therapy (ART) to treat human immunodeficiency virus (HIV) infection, the durability and persistence of latent reservoirs of HIV-infected cells in HIV-infected patients remain obstacles to achieving HIV cure. While technically challenging, the most direct means to eradicate latent reservoirs is to destroy the HIV provirus, thus ensuring that HIV virions are not produced while preserving resident cells. Transcription activator-like effector nucleases (TALEN)─a genome editing method with high DNA targeting efficiency─have been investigated as a potential gene therapy by disrupting the HIV-1 coreceptor CCR5 genes in HIV target cells or HIV proviral DNA in infected cells. However, the transduction and editing efficiencies are low in primary cells and vary by cell type. Using a nanotechnology platform, which we term nanocapsules, the TALEN protein can be effectively delivered into primary cells and escape from endosome/lysosome sequestration. We report that TALEN nanocapsules can effectively mutagenize the HIV-1 proviral DNA integrated into two primary HIV-1 reservoir cells─T cells and macrophages, such that replication and/or reactivation from latency is aborted. We envision that this study provides a useful platform to deliver a wide range of DNA-modifying enzymes for effective HIV therapy.
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Affiliation(s)
- Ming Zhao
- Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Current Address: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, 66047, USA
| | - Jing Wen
- Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Irvin S. Y. Chen
- Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Jia Liu
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China
| | - Yunfeng Lu
- Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA
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Ahmadikhah A, Zarabizadeh H, Nayeri S, Abbasi MS. Advancements in genome editing tools for genetic studies and crop improvement. FRONTIERS IN PLANT SCIENCE 2025; 15:1370675. [PMID: 39963359 PMCID: PMC11830681 DOI: 10.3389/fpls.2024.1370675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 12/31/2024] [Indexed: 02/20/2025]
Abstract
The rapid increase in global population poses a significant challenge to food security, compounded by the adverse effects of climate change, which limit crop productivity through both biotic and abiotic stressors. Despite decades of progress in plant breeding and genetic engineering, the development of new crop varieties with desirable agronomic traits remains a time-consuming process. Traditional breeding methods often fall short of addressing the urgent need for improved crop varieties. Genome editing technologies, which enable precise modifications at specific genomic loci, have emerged as powerful tools for enhancing crop traits. These technologies, including RNA interference, Meganucleases, ZFNs, TALENs, and CRISPR/Cas systems, allow for the targeted insertion, deletion, or alteration of DNA fragments, facilitating improvements in traits such as herbicide and insect resistance, nutritional quality, and stress tolerance. Among these, CRISPR/Cas9 stands out for its simplicity, efficiency, and ability to reduce off-target effects, making it a valuable tool in both agricultural biotechnology and plant functional genomics. This review examines the functional mechanisms and applications of various genome editing technologies for crop improvement, highlighting their advantages and limitations. It also explores the ethical considerations associated with genome editing in agriculture and discusses the potential of these technologies to contribute to sustainable food production in the face of growing global challenges.
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Affiliation(s)
- Asadollah Ahmadikhah
- Department of Cellular and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
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Zhang Y, Duan X, Xue F, Zhou X, Yuan Q, Yang X. Effects of Minocycline on Early Wound Healing after Implant Placement: An In Vitro and Randomized Clinical Study. Clin Oral Implants Res 2025; 36:265-277. [PMID: 39563194 DOI: 10.1111/clr.14380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 09/25/2024] [Accepted: 11/04/2024] [Indexed: 11/21/2024]
Abstract
OBJECTIVE To determine the in vitro effects of minocycline on human gingival fibroblasts (HGFs), its clinical impact on early wound healing after implant placement, and its potential mechanism of action. METHODS First, we evaluated the in vitro proliferation, migration, and collagen production of HGFs treated with different concentrations of minocycline, as well as the underlying mechanism. Subsequently, we conducted a clinical trial and randomly assigned 40 partially edentulous patients to either the test (minocycline hydrochloride treatment) or control (blank control) group immediately after implant surgery. The early wound healing score (EHS), pain index, gingival index (GI), modified sulcus bleeding index (mSBI), and peri-implant crevicular fluid samples were assessed or collected 3 and/or 7 days after surgery. RESULTS In vitro, 1 μg/mL minocycline promoted the proliferation, migration, and collagen production of HGFs. Minocycline inhibited collagen degradation by downregulating the expression of matrix metalloproteinase-2 (MMP-2) and MMP-14 and upregulating tissue inhibitors of metalloproteinases-2. However, higher concentrations of minocycline, 10 and 100 μg/mL, exhibited adverse effects. In the randomised clinical trial, the test group showed significantly better clinical outcomes compared to the control group, with higher EHS and lower GI, mSBI, concentrations of IL-1β, IL-10, and TNF-α, and relative abundance of Streptococcus and gram-negative anaerobic bacteria. CONCLUSIONS Small doses of minocycline (1 μg/mL) promoted the proliferation and migration of HGFs and inhibited collagen degradation in vitro. Locally delivered minocycline after implant surgery improves clinical outcomes by promoting early wound healing, relieving the inflammatory response, and decreasing early colonisation of gram-negative anaerobic bacteria. TRIAL REGISTRATION This clinical trial was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2100044680).
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Affiliation(s)
- Yanjun Zhang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Implants, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xiaobo Duan
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Implants, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Fei Xue
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Implants, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xinyi Zhou
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Implants, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Quan Yuan
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Implants, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xingmei Yang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Implants, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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LI T, ZHU L, WANG X, TANG J, YANG L, PANG G, LI H, WANG L, DONG Y, ZHAO S, LI Y, LI L. Gut microbial characteristics of the damp-heat constitution: a population-based multicenter cross-sectional study. J TRADIT CHIN MED 2025; 45:140-151. [PMID: 39957168 PMCID: PMC11764936 DOI: 10.19852/j.cnki.jtcm.2025.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 03/11/2024] [Indexed: 02/18/2025]
Abstract
OBJECTIVE To investigate the difference in gut microbiota between population with damp-heat constitution (DHC) and balanced constitution (BC). METHODS A multi-centered cross-sectional case-control study was conducted, which included 249 participants with damp-heat constitution or balanced constitution. Baseline information of participants was collected, and stool samples were collected for gut microbiota analysis. Principal coordinate analysis, linear discriminant analysis effect size analysis, receiver operating characteristic, random forest model, and phylogenetic investigation of communities by reconstruction of unobserved states methods were used to reveal the relationship between gut microbiota and the damp-heat constitution. RESULTS Compared to those in the BC group, the richness and diversity of the microbiota, specifically those of several short-chain fatty acid producing genera such as Barnesiella, Coprobacter, and Butyricimonas, were significantly decreased in the DHC group. Regarding biological functions, flavonoid biosynthesis, propanoate metabolism, and nucleotide sugar metabolism were suppressed, while arachidonic acid metabolism and glutathione metabolism were enriched in the DHC group. Finally, a classifier based on the microbiota was constructed to discriminate between the DHC and BC populations. CONCLUSION The gut microbiota of the DHC population exhibits significantly reduced diversity and is closely related to inflammation, metabolic disorders, and liver steatosis, which is consistent with clinical observations, thus serving as a potential diagnostic tool for traditional Chinese medicine constitution discrimination.
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Affiliation(s)
- Tianxing LI
- 1 Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
- 2 National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Linghui ZHU
- 1 Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
- 2 National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Xueke WANG
- 3 the Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou 450046, China
| | - Jun TANG
- 4 Department of Hepatobiliary Spleen and Stomach, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China
| | - Lingling YANG
- 5 Henna Province Hospital of Traditional Chinese Medicine, Henan 450002, China
| | - Guoming PANG
- 6 Department of Endocrinology, Kaifeng Hospital of traditional Chinese Medicine, Kaifeng 475001, China
| | - Huang LI
- 7 State Key Laboratory of Dampness Syndrome of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Liying WANG
- 8 College of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yang DONG
- 1 Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
- 2 National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Shipeng ZHAO
- 9 Graduate School of China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Yingshuai LI
- 2 National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Lingru LI
- 2 National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
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He Y, Gao S, Jiang L, Yang J. Changes in gut microbiota after gastric cancer surgery: a prospective longitudinal study. Front Oncol 2025; 14:1533816. [PMID: 39911821 PMCID: PMC11794085 DOI: 10.3389/fonc.2024.1533816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 12/27/2024] [Indexed: 02/07/2025] Open
Abstract
Background This study was designed to characterize gut microbiota changes of the patients with gastric cancer before and after the gastrectomy during their hospital staying periods. Methods 16S ribosomal RNA (rRNA) gene sequencing was used to evaluate differences in gut microbiota among patients with gastric cancer before and after the gastrectomy by comparing gut microbiota α diversity, β diversity, and structure composition at different taxonomic levels. Results A total of 120 fecal specimens were collected from 60 patients. There was no significant difference in Chao1 index, Shannon index, and Simpson index before and after gastrectomy (all P > 0.05). At the phylum level, the gut microbiota in the gastrectomy group showed less abundance of Bacteroidota, Synergistota, and Verrucomicrobiota but with higher abundance of Campylobacter, Actinobacteria, and Bacillota. At the genus level, the gut microbiota in the gastrectomy group showed less abundance of flora Bacteroides, Faecalibacterium, Blautia, and Lachnospiraceae nk4a136 group but with higher abundance of Campylobacter, Porphyromona, Finegordia, Dialist, Anaerococcus, and Corynebacterium. Conclusions There was no significant change in the diversity of intestinal flora before and after surgery. However, significant changes in the structure of intestinal flora before and after surgery were occurred.
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Affiliation(s)
| | | | | | - Jie Yang
- Colorectal Cancer Center, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
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Wang X, Li Z, Zhou H, Liu Q, Zhang X, Hu F. Periodontitis Exacerbates Colorectal Cancer by Altering Gut Microbiota-Derived Metabolomics in Mice. J Periodontal Res 2025. [PMID: 39843386 DOI: 10.1111/jre.13380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 12/14/2024] [Accepted: 12/22/2024] [Indexed: 01/24/2025]
Abstract
AIM The correlation between periodontitis and colorectal cancer (CRC) has drawn widespread attention. However, how periodontitis affects CRC progression remains unclear. METHODS C57BL/6 mice were used to establish experimental periodontitis and CRC model. Histological alterations of periodontium and colon were observed by hematoxylin and eosin staining. Micro-computed tomography (micro-CT) was applied to evaluate alveolar bone loss (ABL). Tumor growth was detected by immunofluorescence. Gut bacteria were analyzed using 16S rRNA sequencing. Gas chromatography-mass spectrometry (GC-MS) was performed to observe the alterations of gut microbial metabolites. The detection of associated pathways was carried out using quantitative real-time PCR (qRT-PCR). RESULTS Experimental periodontitis significantly induced increases in tumor number in mice with CRC. Double immunofluorescence for Ki67 and β-catenin, as well as Cyclin D1 and β-catenin, indicated that experimental periodontitis observably promoted tumor growth. 16S rRNA sequencing and untargeted metabolomics analysis displayed that experimental periodontitis altered gut microbial community and metabolite profiles in CRC mice. Notably, we found that experimental periodontitis dramatically increased the level of three oncometabolites (serotonin, adenosine, and spermine) in mice with CRC. CONCLUSION Alterations of gut microbial community and metabolites might be relevant in experimental periodontitis deteriorating CRC.
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Affiliation(s)
- Xiaoxue Wang
- Department of Stomatology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Foshan City, Guangdong Province, China
| | - Zhichao Li
- Department of Stomatology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Foshan City, Guangdong Province, China
| | - Haiquan Zhou
- Department of Stomatology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Foshan City, Guangdong Province, China
| | - Qianyi Liu
- Department of Stomatology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Foshan City, Guangdong Province, China
| | - Xueyang Zhang
- Department of Stomatology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Foshan City, Guangdong Province, China
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou City, Guangdong Province, China
| | - Fei Hu
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou City, Guangdong Province, China
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Luo Q, Chu S, Wu Y, Jin L, Liu R, Xu Y, Yu Y, Jin Y, Houndekon LOEP, Hu H, Zou Y, Huang H, Chen H. Characteristics of tongue coating microbiota in diabetic and non-diabetic kidney patients receiving hemodialysis. BMC Oral Health 2025; 25:104. [PMID: 39833942 PMCID: PMC11748270 DOI: 10.1186/s12903-025-05455-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 01/09/2025] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Tongue-coating microbiota, especially known as the tongue microbiome, holds significant value as both a prospective clinical diagnostic biomarker and therapeutic target, which plays a crucial role in the oral microecological health. However, there is limited understanding of the composition and function of tongue coating microbiota in chronic kidney disease patients undergoing hemodialysis. METHODS Thirty-one non-diabetic hemodialysis patients (nonDM_HD), 29 diabetic hemodialysis patients (DM_HD) and 33 healthy controls (HC) were enrolled. Swabs from tongue coating were collected. The 16S rDNA (V3-V4 region) was sequenced to scrutinize the tongue-coating bacterial microbiome difference. RESULTS Both nonDM_HD and DM_HD showed distinct bacterial communities of oral microbiota compared to HC. The abundance of Streptococcus, Lactobacillus, Ruminococcaceae G1, Ligilactobacillus and Abiotrophia showed a significant increase (p < 0.05) in DM_HD and nonDM_HD compared to HC, while Haemophilus, Lachnoanaerobaculum, Peptostreptococcaceae G1, Peptostreptococcus showed a significant decrease (p < 0.05) respectively. Veillonella, Lactobacillus, Limosilactobacillus etc. may serve as potential biomarkers for DM_HD. While Streptococcus, Ruminococcaceae G1, Actinobacillus, Abiotrophia can be considered alternative biomarkers for nonDM_HD. Moreover, the enriched Haemophilus, Actinomyces, Lachnoanaerobaculum were prominent features of the tongue coating microbiota in HC, which could be used as the potential therapeutic targets of chronic kidney disease. Network analysis revealed a less complex interaction relationship among the tongue coating bacterial microbiota of nonDM_HD and DM_HD. Furthermore, correlations were identified between the microbiome composition and clinical parameters of the individuals. CONCLUSION In conclusion, deciphering the tongue coating microbiota of kidney patients undergoing hemodialysis will helpful in assessing the role of oral microbiota in pathobiology and development of kidney disease, which is expected to become a potential biomarkers and adjuvant therapeutic target.
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Affiliation(s)
- Qiang Luo
- Department of Stomatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, 310006, China
| | - Siyuan Chu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
| | - Yongqun Wu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
| | - Lingling Jin
- Department of Stomatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, 310006, China
| | - Rui Liu
- Department of Stomatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, 310006, China
| | - Yulin Xu
- Department of Stomatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, 310006, China
| | - Yina Yu
- Department of Stomatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, 310006, China
| | - Yawei Jin
- Department of Stomatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, 310006, China
| | | | - Heshen Hu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
| | - Yvchen Zou
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
| | - Hao Huang
- Department of Stomatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, 310006, China.
| | - Haimin Chen
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China.
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You W, Cheng H, Hu X, Song E, Jiang F. Capsaicin Modulates Ruminal Fermentation and Bacterial Communities in Beef Cattle with High-Grain Diet-Induced Subacute Ruminal Acidosis. Microorganisms 2025; 13:84. [PMID: 39858852 PMCID: PMC11767826 DOI: 10.3390/microorganisms13010084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 12/29/2024] [Accepted: 01/03/2025] [Indexed: 01/27/2025] Open
Abstract
This study was developed with the goal of exploring the impact of capsaicin on ruminal fermentation and ruminal bacteria in beef cattle affected by high-grain diet-induced subacute ruminal acidosis (SARA). In total, 18 healthy Simmental crossbred cattle were randomized into three separate groups (n = 6/group): (1) control diet (CON; forage-to-concentrate ratio = 80:20); (2) high-grain diet (SARA; forage-to-concentrate ratio = 20:80); and (3) high-grain diet supplemented with capsaicin (CAP; 250 mg/cattle/day). The study was conducted over a 60-day period. The results showed that the SARA model was successfully induced in the SARA group with a high-grain diet. Relative to the SARA group, the addition of capsaicin elevated the ruminal pH from 5.40 to 6.36 (p < 0.01), and decreased the total volatile fatty acids (VFAs) from 133.95 to 82.86 mmol/L (p < 0.01), aligning closely with the levels observed in the CON group. The addition of capsaicin increased the alpha diversity of ruminal bacteria relative to the SARA group, as evidenced by a lower Simpson index (p < 0.05), together with increases in the Ace, Chao, and Shannon indices (p < 0.05). Bacteroidota and Firmicutes were the most common phyla across all treatment groups, while Prevotella was the predominant genera. The unique bacterial genera (LDA scores > 4) identified within the SARA group comprised Succinivibrionaceae_UCG-001, Succinivibrio, NK4A214_group, Lachnospiraceae_NK3A20_group, and Ruminococcus, which may serve as potential biomarkers for the diagnosis of SARA. The unique genera associated with the CON group included Rikenellaceae_RC9_gut_group, Prevotellaceae_UCG-003, and U29-B03, while those for the CAP group included Succiniclasticum and Prevotellaceae_UCG-004. In summary, these results suggest that dietary capsaicin supplementation can limit the adverse effects of SARA through the modulation of bacterial communities within the rumen, thus altering ruminal fermentation in beef cattle.
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Affiliation(s)
- Wei You
- Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan 250100, China; (W.Y.); (H.C.); (X.H.); (E.S.)
- Shandong Provincial Key Laboratory of Livestock and Poultry Breeding, Jinan 250100, China
| | - Haijian Cheng
- Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan 250100, China; (W.Y.); (H.C.); (X.H.); (E.S.)
- Shandong Provincial Key Laboratory of Livestock and Poultry Breeding, Jinan 250100, China
| | - Xin Hu
- Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan 250100, China; (W.Y.); (H.C.); (X.H.); (E.S.)
- Shandong Provincial Key Laboratory of Livestock and Poultry Breeding, Jinan 250100, China
| | - Enliang Song
- Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan 250100, China; (W.Y.); (H.C.); (X.H.); (E.S.)
- Shandong Provincial Key Laboratory of Livestock and Poultry Breeding, Jinan 250100, China
| | - Fugui Jiang
- Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan 250100, China; (W.Y.); (H.C.); (X.H.); (E.S.)
- Shandong Provincial Key Laboratory of Livestock and Poultry Breeding, Jinan 250100, China
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Jacobs R, Singh P, Smith T, Arbuthnot P, Maepa MB. Prospects of viral vector-mediated delivery of sequences encoding anti-HBV designer endonucleases. Gene Ther 2025; 32:8-15. [PMID: 35606493 DOI: 10.1038/s41434-022-00342-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 05/05/2022] [Accepted: 05/06/2022] [Indexed: 11/09/2022]
Abstract
Available treatment for chronic hepatitis B virus (HBV) infection offers modest functional curative efficacy. The viral replicative intermediate comprising covalently closed circular DNA (cccDNA) is responsible for persistent chronic HBV infection. Hence, current efforts have focused on developing therapies that disable cccDNA. Employing gene editing tools has emerged as an attractive strategy, with the end goal of establishing permanently inactivated cccDNA. Although anti-HBV designer nucleases are effective in vivo, none has yet progressed to clinical trial. Lack of safe and efficient delivery systems remains the limiting factor. Several vectors may be used to deliver anti-HBV gene editor-encoding sequences, with viral vectors being at the forefront. Despite the challenges associated with packaging large gene editor-encoding sequences into viral vectors, advancement in the field is overcoming such limitations. Translation of viral vector-mediated gene editing against HBV to clinical application is within reach. This review discusses the prospects of delivering HBV targeted designer nucleases using viral vectors.
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Affiliation(s)
- Ridhwaanah Jacobs
- Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Prashika Singh
- Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Tiffany Smith
- Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Patrick Arbuthnot
- Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Mohube Betty Maepa
- Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
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Xu R, Zhang Y, Wu T, Liu H, Peng J, Wang Z, Ba T, Zhang B, Li Z, Wei Y. Traffic-related air pollution (TRAP) exposure, lung function, airway inflammation and expiratory microbiota: A randomized crossover study. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025; 289:117545. [PMID: 39788033 DOI: 10.1016/j.ecoenv.2024.117545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 11/24/2024] [Accepted: 12/11/2024] [Indexed: 01/12/2025]
Abstract
Traffic-related air pollution (TRAP) has been linked with numerous respiratory diseases. Recently, lung microbiome is proposed to be characterized with development and progression of respiratory diseases. However, the underlying effects of TRAP exposure on lung microbiome are rarely explored. We conducted a randomized, crossover study among 35 healthy adults, who participated in 2-h exposure treatments in the road or park scenario alternately, to investigate the impact of short-term TRAP exposure on expiratory health. Particle matters (PMs), nitrogen dioxide (NO2), carbon monoxide (CO) and volatile organic compounds (VOCs), lung function, fractional exhaled nitric oxide (FeNO) and lung microbiota were measured. We applied linear mixed-effect models to explore the associations. TRAP including NO2 and CO in the road were about 1.5 times higher than that in the park except for PMs, and total VOCs also showed higher concentrations. We observed elevated difference in FeNO was associated with high TRAP exposure in the road session, but didn't find obvious changes in lung function. The abundance of Lentilactobacillus and Haepmophilus were distinct in the two groups, with significant correlations with changes to PEF and FeNO, respectively. Enrichment pathways related to transcription, amino acid and carbohydrate metabolism were altered following high TRAP exposure, suggesting TRAP contributed to the respiratory disease by changing metabolism of lung microbes. Our findings reveal VOCs in the road are another key air pollutant and provide novel mechanism for the respiratory effects of TRAP from the perspective of microbiome.
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Affiliation(s)
- Rongrong Xu
- College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China
| | - Yanping Zhang
- Institute of Atmospheric Environment, Chinese Research Academy of Environmental Science
| | - Tingting Wu
- College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China
| | - Hao Liu
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China
| | - Jianhao Peng
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China
| | - Zhanshan Wang
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China
| | - Te Ba
- Department of Stomatology, Aviation General Hospital, Beijing, China
| | - Baorong Zhang
- Department of Stomatology, Aviation General Hospital, Beijing, China
| | - Zhigang Li
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.
| | - Yongjie Wei
- College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.
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22
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Li P, Zhang H, Gao X, Chen L, Chen H, Yuan S, Chen W, Dai M. Difference in fecal and oral microbiota between pancreatic cancer and benign/low-grade malignant tumor patients. BMC Microbiol 2024; 24:527. [PMID: 39695939 DOI: 10.1186/s12866-024-03687-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 12/04/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Significant gaps exist in understanding the gastrointestinal microbiota in patients with pancreatic cancer (PCA) versus benign or low-grade malignant pancreatic tumors (NPCA). This study aimed to analyze these microbiota characteristics and explore their potential use in distinguishing malignant pancreatic lesions. METHODS Between September 2020 and May 2024, fecal and oral samples were collected from 121 patients undergoing surgical resection or diagnostic biopsy of pancreatic lesions, including 75 patients with PCA and 46 patients with NPCA, and 16s rRNA sequencing was performed. Random forest models based using fecal and oral microbiota data were developed to diagnose PCA and NPCA, with performance assessed using the leave-one-out cross validation method. RESULTS The Shannon index and PCoA analysis revealed significant differences in oral microbiota composition between PCA and NPCA (p < 0.001 and p = 0.001, respectively). Fecal microbiome richness differed significantly (p = 0.02), though composition similarity was noted (p = 0.238). LEfSe identified 16 and 23 genera with significant differences in fecal and oral microbiomes, respectively. Random forest classifiers based on fecal and oral microbiota achieved areas under the curves (AUCs) of 89.4% and 96.3%, respectively, for distinguishing PCA and NPCA. In the mucinous tumor cohort, oral and fecal microbiome classifiers outperformed CA19-9, yielding AUCs of 83.0% and 85.2%, respectively. CONCLUSION Fecal and oral microbiota compositions were significantly different between PCA and NPCA patients. Random forest classifiers utilizing fecal and oral microbiota data effectively distinguish between benign or low-grade malignant and malignant pancreatic lesions.
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Affiliation(s)
- Pengyu Li
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Hanyu Zhang
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Xingyu Gao
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Lixin Chen
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Haomin Chen
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Shuai Yuan
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Weijie Chen
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Menghua Dai
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
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Mamatha Bhanu LS, Kataki S, Chatterjee S. CRISPR: New promising biotechnological tool in wastewater treatment. J Microbiol Methods 2024; 227:107066. [PMID: 39491556 DOI: 10.1016/j.mimet.2024.107066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 10/30/2024] [Accepted: 10/30/2024] [Indexed: 11/05/2024]
Abstract
The increasing demand for water resources with increase in population has sparked interest in reusing produced water, especially in water-scarce regions. The clustered regularly interspaced short palindromic repeats (CRISPR) technology is an emerging genome editing tool that has the potential to trigger significant impact with broad application scope in wastewater treatment. We provide a comprehensive overview of the scope of CRISPR-Cas based tool for treating wastewater that may bring new scope in wastewater management in future in controlling harmful contaminants and pathogens. As an advanced versatile genome engineering tool, focusing on particular genes and enzymes that are accountable for pathogen identification, regulation of antibiotic/antimicrobial resistance, and enhancing processes for wastewater bioremediation constitute the primary focal points of research associated with this technology. The technology is highly recommended for targeted mutations to incorporate desirable microalgal characteristics and the development of strains capable of withstanding various wastewater stresses. However, concerns about gene leakage from strains with modified genome and off target mutations should be considered during field application. A comprehensive interdisciplinary approach involving various fields and an intense research focus concerning delivery systems, target genes, detection, environmental conditions, and monitoring at both lab and ground level should be considered to ensure its successful application in sustainable and safe wastewater treatment.
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Affiliation(s)
- L S Mamatha Bhanu
- Department of Biotechnology, Yuvaraja's College, University of Mysore, Mysuru, Karnataka, India
| | - Sampriti Kataki
- Biodegradation Technology Division, Defence Research Laboratory, DRDO, Tezpur, Assam, India
| | - Soumya Chatterjee
- Biodegradation Technology Division, Defence Research Laboratory, DRDO, Tezpur, Assam, India.
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Wang Z, Yu Z, Yuan W, Gu Y, Xiu X, Song L. Unique genital microbiota in male lichen sclerosus urethral stricture associated with urine exposure. BMC Microbiol 2024; 24:508. [PMID: 39614166 DOI: 10.1186/s12866-024-03659-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 11/18/2024] [Indexed: 12/01/2024] Open
Abstract
BACKGROUND Lichen sclerosus (LS) is a chronic inflammatory cicatricial skin disease that can lead to urethral stricture or even malignant transformation and the etiology is still unknown. This study comparatively analyzed the balanopreputial swab and urine microbiota simultaneously between male patients with LS urethral stricture (LSUS) and non-LS urethral stricture (non-LSUS). METHODS We prospectively included 31 male patients with LSUS and 30 with non-LSUS in this case-control study. Midstream urine samples and balanopreputial swabs were collected from each patient for the 16S V3-V4 hypervariable region sequencing. Operational taxonomic units were defined using a > 97% sequence similarity threshold. We compared the differences in alpha diversity, beta diversity, and microbial structure between the two groups. RESULTS Whether in swab or urine samples, there was no significant difference in alpha diversity between the two groups. Swab samples showed a significant difference in beta diversity (p = 0.001). For all individuals, composition analyses showed that the most abundant phyla were Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes in both samples. Additionally, the microbial communities of swab samples were significantly more similar to the communities of urine samples in the LSUS group (p = 0.047). CONCLUSIONS Microbiota showed significant variation between LSUS and non-LSUS groups, suggesting that microecological imbalance may be closely related to the occurrence of LS. Urinary irritation may be related to the unique microbiota on the genital skin of patients with LSUS.
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Affiliation(s)
- Zeyu Wang
- Department of Urology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Eastern Institute of Urologic Reconstruction, Shanghai, China
| | - Zhenwei Yu
- Department of Urology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Eastern Institute of Urologic Reconstruction, Shanghai, China
| | - Wei Yuan
- Department of Urology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Eastern Institute of Urologic Reconstruction, Shanghai, China
| | - Yubo Gu
- Department of Urology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Eastern Institute of Urologic Reconstruction, Shanghai, China
| | - Xianjie Xiu
- Department of Urology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Eastern Institute of Urologic Reconstruction, Shanghai, China
| | - Lujie Song
- Department of Urology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Shanghai Eastern Institute of Urologic Reconstruction, Shanghai, China.
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Liu Y, Zhang Y, Zhang J, Ren S, Cao Q, Kong H, Xu Q, Liu R. High-fat diet stimulated butyric acid metabolism dysbiosis, altered microbiota, and aggravated inflammatory response in collagen-induced arthritis rats. Nutr Metab (Lond) 2024; 21:95. [PMID: 39563394 DOI: 10.1186/s12986-024-00869-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 11/06/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND Research has demonstrated that obesity may be associated with rheumatoid arthritis (RA). In addition, Dysbiosis of intestinal microbiota and their metabolites has been linked to the occurrence and development of RA and obesity. However, the mechanism by which obesity affects RA remains unclear.In this study, we explored the impact of high fat diet(HFD) on collagen-induced arthritis (CIA) rats and revealed its mechanisms based on gut microbiota and metabolomics. METHODS Based on diet and modeling, rats were divided into normal group (Con), CIA model group, HFD group (HFD), and HFD + CIA group (HCIA). The effect of HFD on arthritis in CIA rats were investigated based on the arthritis index (AI), weight, blood lipid levels, and inflammatory cytokines. Moreover, HE staining and micro-CT were performed to evaluated the effect of HFD on the pathology of joints and synovial tissues in CIA rats.16S rRNA amplicon sequencing and liquid chromatography-mass spectrometry (LC-MS) were employed to explore changes in gut microbiota and short-chain fatty acids (SCFAs). RESULTS The AI scores, inflammatory cytokines and bone destruction parameters in the HCIA group were significantly higher than those in the other three groups. The results of 16S rRNA amplicon sequencing and metabolomics showed that compared with the other three groups, the expression of g_Muribaculaceae and butyric acid were reduced in the HCIA group. Spearman and linear correlation analyses revealed a positive correlation between g_Muribaculaceae abundance and butyric acid levels. CONCLUSIONS HFD stimulated butyric acid metabolism dysbiosis, altered microbiota, and aggravated inflammatory response in CIA rats.
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Affiliation(s)
- Yantong Liu
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Yang Zhang
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Jie Zhang
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Shuang Ren
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Qi Cao
- School of Acupuncture-Moxibustion and Tuina, Liaoning University of Traditional Chinese Medicine, Shenyang, 110001, China
| | - Hongxi Kong
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Qiangqiang Xu
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Ruoshi Liu
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, 110001, China.
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Shi M, Xue Q, Xie J, Yang Q, Tong J, Zhu J, Gao Y, Ma X, Wu D, Li Z. Protective effect of Shenqi Wenfei Formula against lipopolysaccharide/cigarette smoke-induced COPD in Rat based on gut microbiota and network pharmacology analysis. Front Microbiol 2024; 15:1441015. [PMID: 39629210 PMCID: PMC11611827 DOI: 10.3389/fmicb.2024.1441015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 10/30/2024] [Indexed: 12/07/2024] Open
Abstract
Introduction The incidence of chronic obstructive pulmonary disease (COPD) appears to be increasing and evidence suggests that the intestinal flora may play a causative role in its development. Previous studies found that the Shenqi Wenfei Formula (SQWF) can regulate pyroptosis via the NLRP3/GSDMD pathway, thereby reducing the inflammatory response in the lungs of COPD model rats. However, there is no information on whether the drug's effects are associated with intestinal flora. Therefore, this study investigates whether the effects of SQWF are mediated through the regulation of intestinal flora, aiming to elucidate the underlying mechanisms of its therapeutic impact on COPD. Methods COPD was induced in rats using lipopolysaccharide and cigarette smoke, followed by intragastric administration of SQWF or physiological saline The targets of SQWF, associated signaling pathways, and key bacterial groups were investigated using 16S rRNA sequencing, network pharmacology, and bioinformatics techniques. The prediction results were validated using quantitative reverse transcription PCR, western blotting, and immunofluorescence, among other methods. Results SQWF treatment was found to alleviate COPD in model rats. Treatment was also observed to restore the balance of the intestinal flora in the rats, especially by reducing the abundance of g_Parabacteroides. Bioinformatics predictions identified g_Parabacteroides metabolites, RelA, HDAC1, and enriched neutrophil extracellular trap formation pathways as core targets of SQWF in COPD. qRT-PCR and Western blotting results showed that SQWF treatment reduced ReLA and HDAC1 mRNA and protein expression, along with decreased myeloperoxidase and neutrophil elastase levels in the nucleus. Conclusion Treatment with SQWF was found to restore the imbalance of intestinal g_Parabacteroides in COPD and also regulate the expression of the ReLA and HDAC1 genes, thereby reducing pulmonary neutrophil extracellular traps and alleviating lung inflammation.
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Affiliation(s)
- Mengyao Shi
- Anhui University of Chinese Medicine, Hefei, China
| | - Qian Xue
- Anhui University of Chinese Medicine, Hefei, China
| | - Jinghui Xie
- Anhui University of Chinese Medicine, Hefei, China
| | - Qinjun Yang
- Anhui University of Chinese Medicine, Hefei, China
- Chinese Medicine Respiratory Disease Prevention Institute, Hefei, China
- Anhui Province Key Laboratory of the Application and Transformation of Traditional Chinese Medicine in the Prevention and Treatment of Major Pulmonary Diseases, Hefei, China
| | - Jiabing Tong
- Anhui University of Chinese Medicine, Hefei, China
- Chinese Medicine Respiratory Disease Prevention Institute, Hefei, China
- Anhui Province Key Laboratory of the Application and Transformation of Traditional Chinese Medicine in the Prevention and Treatment of Major Pulmonary Diseases, Hefei, China
| | - Jie Zhu
- Anhui University of Chinese Medicine, Hefei, China
- Chinese Medicine Respiratory Disease Prevention Institute, Hefei, China
- Anhui Province Key Laboratory of the Application and Transformation of Traditional Chinese Medicine in the Prevention and Treatment of Major Pulmonary Diseases, Hefei, China
| | - Yating Gao
- Chinese Medicine Respiratory Disease Prevention Institute, Hefei, China
- Anhui Province Key Laboratory of the Application and Transformation of Traditional Chinese Medicine in the Prevention and Treatment of Major Pulmonary Diseases, Hefei, China
- First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
| | - Xiao Ma
- Anhui University of Chinese Medicine, Hefei, China
| | - Di Wu
- Anhui University of Chinese Medicine, Hefei, China
- First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
| | - Zegeng Li
- Anhui University of Chinese Medicine, Hefei, China
- Chinese Medicine Respiratory Disease Prevention Institute, Hefei, China
- Anhui Province Key Laboratory of the Application and Transformation of Traditional Chinese Medicine in the Prevention and Treatment of Major Pulmonary Diseases, Hefei, China
- First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
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Li Y, Lin M, Wang G, Han L. Atractylodes macrocephala polysaccharides shield a D-galactose-induced aging model via gut microbiota modulation. Int J Biol Macromol 2024; 281:136205. [PMID: 39357696 DOI: 10.1016/j.ijbiomac.2024.136205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 09/21/2024] [Accepted: 09/30/2024] [Indexed: 10/04/2024]
Abstract
This study explored the effect of a heteropolysaccharide (RAMP) on aging model mice and the importance of changes in the gut microbiota mediated by RAMP for the first time. The findings revealed that RAMP exerted protective effects on cognitive decline and oxidative stress in mice subjected to D-gal-induced aging, potentially by regulating the intestinal flora, according to the results of the Morris water maze test; brain and immune organ indices; hematoxylin and eosin-stained cerebral cortex images; transmission electron microscopy analysis of cortical neurons; and biochemical index measurements. In addition, 16S rRNA sequencing revealed notable changes in the abundance of Acidobacteriota, Anaerovoracaceae, and GCA-900066575 in the mouse model, all of which were abrogated by RAMP. These findings confirm that RAMP regulates the composition of mouse intestinal microorganisms. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional analyses linked these changes to 27 metabolic pathways, including those of the nervous system. Furthermore, metabolomics analysis revealed four RAMP-regulated metabolites related to lipid metabolism (2-dodecylbenzenesulfonic acid, N-undecylbenzenesulfonic acid, aspartyl-isoleucine, and 1-palmitoyl-2-(5-oxo-valeroyl)-sn-glycero-3-phosphate), suggesting that the mechanism potentially associated with lipid metabolism regulation. This study provides novel insights into the antiaging mechanisms of RAMP, suggesting its potential use in antiaging treatments.
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Affiliation(s)
- Yunzhi Li
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.
| | - Min Lin
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China
| | - Guodong Wang
- School of Pharmacy, Wannan Medical College, Wuhu 241002, China
| | - Lan Han
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.
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Castillo SR, Simone BW, Clark KJ, Devaux P, Ekker SC. Unconstrained Precision Mitochondrial Genome Editing with αDdCBEs. Hum Gene Ther 2024; 35:798-813. [PMID: 39212664 PMCID: PMC11511777 DOI: 10.1089/hum.2024.073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 08/05/2024] [Indexed: 09/04/2024] Open
Abstract
DddA-derived cytosine base editors (DdCBEs) enable the targeted introduction of C•G-to-T•A conversions in mitochondrial DNA (mtDNA). DdCBEs work in pairs, with each arm composed of a transcription activator-like effector (TALE), a split double-stranded DNA deaminase half, and a uracil glycosylase inhibitor. This pioneering technology has helped improve our understanding of cellular processes involving mtDNA and has paved the way for the development of models and therapies for genetic disorders caused by pathogenic mtDNA variants. Nonetheless, given the intrinsic properties of TALE proteins, several target sites in human mtDNA are predicted to remain out of reach to DdCBEs and other TALE-based technologies. Specifically, due to the conventional requirement for a thymine immediately upstream of the TALE target sequences (i.e., the 5'-T constraint), over 150 loci in the human mitochondrial genome are presumed to be inaccessible to DdCBEs. Previous attempts at circumventing this requirement, either by developing monomeric DdCBEs or utilizing DNA-binding domains alternative to TALEs, have resulted in suboptimal specificity profiles with reduced therapeutic potential. Here, aiming to challenge and elucidate the relevance of the 5'-T constraint in the context of DdCBE-mediated mtDNA editing, and to expand the range of motifs that are editable by this technology, we generated DdCBEs containing TALE proteins engineered to recognize all 5' bases. These modified DdCBEs are herein referred to as αDdCBEs. Notably, 5'-T-noncompliant canonical DdCBEs efficiently edited mtDNA at diverse loci. However, they were frequently outperformed by αDdCBEs, which exhibited significant improvements in activity and specificity, regardless of the most 5' bases of their TALE binding sites. Furthermore, we showed that αDdCBEs are compatible with the enhanced DddAtox variants DddA6 and DddA11, and we validated TALE shifting with αDdCBEs as an effective approach to optimize base editing outcomes. Overall, αDdCBEs enable efficient, specific, and unconstrained mitochondrial base editing.
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Affiliation(s)
- Santiago R. Castillo
- Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, Minnesota, USA
- Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Brandon W. Simone
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA
| | - Karl J. Clark
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA
| | - Patricia Devaux
- Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, Minnesota, USA
- Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Stephen C. Ekker
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA
- Department of Pediatrics and Department of Molecular Biosciences, Dell Medical School, The University of Texas at Austin, Austin, Texas, USA
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Rao G, Song WL, Yan SZ, Chen SL. Unraveling the distribution pattern and driving forces of soil microorganisms under geographic barriers. Appl Environ Microbiol 2024; 90:e0135924. [PMID: 39171904 PMCID: PMC11409670 DOI: 10.1128/aem.01359-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 07/31/2024] [Indexed: 08/23/2024] Open
Abstract
The Altai Mountains (ALE) and the Greater Khingan Mountains (GKM) in northern China are forest regions dominated by coniferous trees. These geographically isolated regions provide an ideal setting for studying microbial biogeographic patterns. In this study, we employed high-throughput techniques to obtain DNA sequences of soil myxomycetes, bacteria, and fungi and explored the mechanisms underlying the assembly of both local and cross-regional microbial communities in relation to environmental factors. Our investigation revealed that the environmental heterogeneity in ALE and GKM significantly affected the succession and assembly of soil bacterial communities at cross-regional scales. Specifically, the optimal environmental factors affecting bacterial Bray-Curtis similarity were elevation and temperature seasonality. The spatial factors and climate change impact on bacterial communities under the geographical barriers surpassed that of local soil microenvironments. The assembly pattern of bacterial communities transitions from local drift to cross-regional heterogeneous selection. Environmental factors had a relatively weak influence on myxomycetes and fungi. Both soil myxomycetes and fungi faced considerable dispersal limitation at local and cross-regional scales, ultimately leading to weak geographical distribution patterns.IMPORTANCEThe impact of environmental selection and dispersal on the soil microbial spatial distribution is a key concern in microbial biogeography, particularly in large-scale geographical patterns. However, our current understanding remains limited. Our study found that soil bacteria displayed a distinct cross-regional geographical distribution pattern, primarily influenced by environmental selection. Conversely, the cross-regional geographical distribution patterns of soil myxomycetes and fungi were relatively weak. Their composition exhibited a weak association with the environment at local and cross-regional scales, with assembly primarily driven by dispersal limitation.
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Affiliation(s)
- Gu Rao
- School of Life Sciences, Nanjing Normal University, Nanjing, China
| | - Wen-Long Song
- School of Life Sciences, Nanjing Normal University, Nanjing, China
| | - Shu-Zhen Yan
- School of Life Sciences, Nanjing Normal University, Nanjing, China
| | - Shuang-Lin Chen
- School of Life Sciences, Nanjing Normal University, Nanjing, China
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Ma Y, Shen Y, Zhou X, Ma H, Lan J, Fu B, Xue Q. Biological Decline of Alfalfa Is Accompanied by Negative Succession of Rhizosphere Soil Microbial Communities. PLANTS (BASEL, SWITZERLAND) 2024; 13:2589. [PMID: 39339564 PMCID: PMC11434760 DOI: 10.3390/plants13182589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Revised: 09/11/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024]
Abstract
The growth and biological decline of alfalfa may be linked to the rhizosphere microbiome. However, plant-microbe interactions in the rhizosphere of alfalfa and associated microbial community variations with stand age remain elusive. This study explored the successional pattern of rhizosphere microbial communities across different aged alfalfa stands and its relationship with alfalfa decline. Rhizosphere soils were collected from 2- and 6-year-old alfalfa stands. Control soils were collected from interspaces between alfalfa plants in the same stands. Soil bacterial and fungal communities were characterized by 16S and ITS rRNA gene sequencing, respectively. Specific microbial taxa colonized the rhizosphere soils, but not the control soils. The rhizosphere-specific taxa mainly included potentially beneficial genera (e.g., Dechloromonas, Verrucomicrobium) in the young stand and harmful genera (e.g., Peziza, Campylocarpon) in the old stand. Alfalfa roots regulated soil microbial communities by selective promotion or inhibition of distinct taxa. The majority of time-enriched taxa were reported as harmful fungi, whose relative abundances were negatively correlated with plant traits. Time-depleted taxa were mostly known as beneficial bacteria, which had relative abundances positively correlated with plant traits. The relative abundances of functional bacterial genes associated with vancomycin biosynthesis, zeatin biosynthesis, and amino acid metabolism trended lower in rhizosphere soils from the old stand. An upward trend was observed for fungal pathogens and wood saprotrophs with increasing stand age. The results suggest that root activity drives the negative succession of rhizosphere microbial communities during alfalfa decline in old stands.
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Affiliation(s)
- Yuanyuan Ma
- College of Forestry and Prataculture, Ningxia University, Yinchuan 750021, China; (Y.M.); (H.M.); (J.L.); (B.F.)
- Ningxia Rural Science and Technology Development Center, Yinchuan 750001, China;
| | - Yan Shen
- College of Forestry and Prataculture, Ningxia University, Yinchuan 750021, China; (Y.M.); (H.M.); (J.L.); (B.F.)
| | - Xiaoping Zhou
- Ningxia Rural Science and Technology Development Center, Yinchuan 750001, China;
| | - Hongbin Ma
- College of Forestry and Prataculture, Ningxia University, Yinchuan 750021, China; (Y.M.); (H.M.); (J.L.); (B.F.)
| | - Jian Lan
- College of Forestry and Prataculture, Ningxia University, Yinchuan 750021, China; (Y.M.); (H.M.); (J.L.); (B.F.)
| | - Bingzhe Fu
- College of Forestry and Prataculture, Ningxia University, Yinchuan 750021, China; (Y.M.); (H.M.); (J.L.); (B.F.)
| | - Quanhong Xue
- College of Natural Resources and Environment, Northwest A&F University, Yangling 712100, China;
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Yang F, Ma Q, Zhang X, Shang Y, Ngando FJ, Ren L, Cai J. The gut bacterial composition across life stages of Sarcophaga peregrina (Diptera: Sarcophagidae) and the effects of amikacin on their development. JOURNAL OF MEDICAL ENTOMOLOGY 2024; 61:1093-1104. [PMID: 38902886 DOI: 10.1093/jme/tjae071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 05/05/2024] [Accepted: 05/14/2024] [Indexed: 06/22/2024]
Abstract
Insects and microorganisms, ubiquitous organisms in the natural world, have developed intricate relationships throughout their evolutionary histories. However, most studies have concentrated on specific time points or life stages, but some limited studies have investigated the dynamics of microbial diversity within insects across life stages. Here, 16S rDNA sequencing technology was used to investigate the gut bacterial community across the life stages of Sarcophaga peregrina (Robineau-Desvoidy) (Diptera: Sarcophagidae). The results revealed that the gut bacterial diversity of S. peregrina varied with life stage and showed similarity in the nearby life stages. Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes were the dominant phyla in S. peregrina. Genera such as Providencia, Ignatzschineria, and Myroides are implicated in potentially pivotal roles during the developmental processes of this flesh fly. Furthermore, the effects of amikacin on the growth and development of S. peregrina were not statistically significant. However, we did observe significant changes at the protein level, which suggests a close association between protein-level alterations and growth and development. Additionally, we speculate that S. peregrina regulates its nutritional status during nonfeeding stages to meet the demands of eclosion. This study represents the first comprehensive examination of the intestinal bacterial composition across various life stages of S. peregrina. Our findings deepen our understanding of the gut microbiota in this flesh fly and lay the groundwork for further exploration into the intricate interactions between microorganisms and insects.
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Affiliation(s)
- Fengqin Yang
- Department of Forensic Science, School of Basic Medical Sciences, Central South University, Hunan, Changsha, China
| | - Qiongshan Ma
- Department of Forensic Science, School of Basic Medical Sciences, Central South University, Hunan, Changsha, China
| | - Xiangyan Zhang
- Department of Forensic Science, School of Basic Medical Sciences, Central South University, Hunan, Changsha, China
| | - Yanjie Shang
- Department of Forensic Science, School of Basic Medical Sciences, Central South University, Hunan, Changsha, China
| | - Fernand Jocelin Ngando
- Department of Forensic Science, School of Basic Medical Sciences, Central South University, Hunan, Changsha, China
| | - Lipin Ren
- Department of Forensic Science, School of Basic Medical Sciences, Central South University, Hunan, Changsha, China
| | - Jifeng Cai
- Department of Forensic Science, School of Basic Medical Sciences, Central South University, Hunan, Changsha, China
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Wang X, Li H, Yang Y, Wu Z, Wang Z, Li D, Xia W, Zou S, Liu Y, Wang F. Geographic and environmental impacts on gut microbiome in Himalayan langurs ( Semnopithecus schistaceus) and Xizang macaques ( Macaca mulatta vestita). Front Microbiol 2024; 15:1452101. [PMID: 39296299 PMCID: PMC11408304 DOI: 10.3389/fmicb.2024.1452101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 08/20/2024] [Indexed: 09/21/2024] Open
Abstract
Introduction Gut microbiome plays a crucial role in the health of wild animals. Their structural and functional properties not only reflect the host's dietary habits and habitat conditions but also provide essential support for ecological adaptation in various environments. Methods This study investigated the gut microbiome of Himalayan langurs (Semnopithecus schistaceus) and Xizang macaques (Macaca mulatta vestita) across different geographic regions using 16S rRNA gene and metagenomic sequencing. Results Results showed distinct clustering patterns in gut microbiota based on geographic location. Soil had an insignificant impact on host gut microbiome. Himalayan langurs from mid-altitude regions exhibited higher levels of antibiotic resistance genes associated with multidrug resistance, while Xizang macaques from high-altitude regions showed a broader range of resistance genes. Variations in carbohydrate-active enzymes and KEGG pathways indicated unique metabolic adaptations to different environments. Discussion These findings provide valuable insights into the health and conservation of these primates and the broader implications of microbial ecology and functional adaptations in extreme conditions.
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Affiliation(s)
- Xueyu Wang
- Key Laboratory of Conservation Biology of Rhinopithecus roxellana (Department of Education of Sichuan Province), China West Normal University, Nanchong, China
| | - Hong Li
- Key Laboratory of Conservation Biology of Rhinopithecus roxellana (Department of Education of Sichuan Province), China West Normal University, Nanchong, China
| | - Yumin Yang
- Institute of Agricultural Resources and Environment, Sichuan Academy of Agricultural Sciences, Chengdu, China
| | - Zhijiu Wu
- Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Zhixiang Wang
- Key Laboratory of Conservation Biology of Rhinopithecus roxellana (Department of Education of Sichuan Province), China West Normal University, Nanchong, China
| | - Dayong Li
- Key Laboratory of Conservation Biology of Rhinopithecus roxellana (Department of Education of Sichuan Province), China West Normal University, Nanchong, China
| | - Wancai Xia
- Key Laboratory of Conservation Biology of Rhinopithecus roxellana (Department of Education of Sichuan Province), China West Normal University, Nanchong, China
| | - Shuzhen Zou
- Key Laboratory of Conservation Biology of Rhinopithecus roxellana (Department of Education of Sichuan Province), China West Normal University, Nanchong, China
| | - Yujia Liu
- Key Laboratory of Conservation Biology of Rhinopithecus roxellana (Department of Education of Sichuan Province), China West Normal University, Nanchong, China
| | - Fan Wang
- Key Laboratory of Conservation Biology of Rhinopithecus roxellana (Department of Education of Sichuan Province), China West Normal University, Nanchong, China
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Zhang J, Zhang R, Chen Y, Guo X, Ren Y, Wang M, Li X, Huang Z, Zhu W, Yu K. Indole-3-aldehyde Alleviates High-Fat Diet-Induced Gut Barrier Disruption by Increasing Intestinal Stem Cell Expansion. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:18930-18941. [PMID: 39146439 DOI: 10.1021/acs.jafc.4c02381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/17/2024]
Abstract
High-fat diet (HFD) feeding is known to cause intestinal barrier disruption, thereby triggering severe intestinal inflammatory disease. Indole-3-aldehyde (IAld) has emerged as a potential candidate for mitigating inflammatory responses and maintaining intestinal homeostasis. However, the role of IAld in the HFD-related intestinal disruption remains unclear. In this study, 48 7 week-old male C57BL/6J mice were assigned to four groups: the normal chow diet (NCD) group received a NCD; the HFD group was fed an HFD; the HFD + IAld200 group was supplemented with 200 mg/kg IAld in the HFD; and the HFD + IAld600 group was supplemented with 600 mg/kg IAld in the HFD. The results showed that dietary IAld supplementation ameliorated fat accumulation and metabolic disorders, which are associated with reduced intestinal permeability. This reduction potentially led to decreased systemic inflammation and enhanced intestinal barrier function in HFD-fed mice. Furthermore, we found that IAld promoted intestinal stem cell (ISC) proliferation by activating aryl hydrocarbon receptors (AHRs) in vivo and ex vivo. These findings suggest that IAld restores the HFD-induced intestinal barrier disruption by promoting AHR-mediated ISC proliferation.
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Affiliation(s)
- Jiaqi Zhang
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Ruofan Zhang
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
- Animal Health Inspection Institute of Suzhou, Wujiang District, Suzhou 215200, China
| | - Yahui Chen
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Xin Guo
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Yuting Ren
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Mengting Wang
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Xuan Li
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Zan Huang
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Weiyun Zhu
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Kaifan Yu
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
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Zhou H, Yu K, Deng C, Wu B, Gao Y. Deterministic processes influence bacterial more than fungal community assembly during the development of biological soil crusts in the desert ecosystem. Front Microbiol 2024; 15:1404602. [PMID: 39247695 PMCID: PMC11377341 DOI: 10.3389/fmicb.2024.1404602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 08/13/2024] [Indexed: 09/10/2024] Open
Abstract
Biological soil crusts (biocrusts) constitute a crucial biological component of the soil surface in arid and semi-arid ecosystems. Understanding the variations in soil microbial community assembly across biocrust successional stages is essential for a deeper comprehension of microbial biodiversity and desert ecosystem functioning. However, knowledge about the mechanisms of microbial community assembly and the factors influencing its development remains limited. In this study, we utilized amplicons sequencing to assess the compositions of bacterial and fungal communities in bare sand and three types of biocrusts (light cyanobacterial biocrusts, dark cyanobacterial biocrusts, and moss crusts). Subsequently, we analyzed the ecological processes shaping microbial community composition and structure, along with the influencing factors. Our results revealed a significant increase in bacterial diversity and no significant changes in fungal diversity during biocrust development. The relative abundances of the copiotrophic bacteria (e.g., Actinobacteria, Acidobacteria, and Bacteroidetes) showed significant increases, while oligotrophic bacteria (e.g., Proteobacteria and Firmicutes) decreased over time. Moreover, the relative abundances of Ascomycota, which exhibit strong resistance to adverse environmental conditions, significantly decreased, whereas Basidiomycota, known for their ability to degrade lignin, significantly increased throughout biocrust development. Additionally, stochastic processes (dispersal limitation and drift) predominantly drove the assemblies of both bacterial and fungal communities. However, the relative importance of deterministic processes (homogeneous selection) in bacterial assembly increased during biocrust development. Structural equation modeling indicated that bacterial community assembly was primarily related to soil water content, whereas fungal community assembly was primarily related to total organic carbon. These findings provide a scientific foundation for investigating the formation and development of biocrusts, and further insights into the conservation and sustainable management of biocrust resources under future climate change scenarios.
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Affiliation(s)
- Hong Zhou
- Academy of Agriculture and Forestry Sciences, Qinghai University, Xining, China
- Institute of Ecological Conservation and Restoration, Chinese Academy of Forestry, Beijing, China
- Qinghai Guinan Desert Ecosystem Positioning Observation and Research Station, National Forestry and Grassland Administration, Beijing, China
- Key Laboratory of Desert Ecosystem and Global Change, State Administration of Forestry and Grassland, Beijing, China
| | - Ke Yu
- School of Environment and Energy, Shenzhen Graduate School, Peking University, Shenzhen, China
| | - Chunfang Deng
- School of Environment and Energy, Shenzhen Graduate School, Peking University, Shenzhen, China
| | - Bo Wu
- Institute of Ecological Conservation and Restoration, Chinese Academy of Forestry, Beijing, China
- Key Laboratory of Desert Ecosystem and Global Change, State Administration of Forestry and Grassland, Beijing, China
- Institute of Desertification Studies, Chinese Academy of Forestry, Beijing, China
| | - Ying Gao
- Institute of Ecological Conservation and Restoration, Chinese Academy of Forestry, Beijing, China
- Key Laboratory of Desert Ecosystem and Global Change, State Administration of Forestry and Grassland, Beijing, China
- Institute of Desertification Studies, Chinese Academy of Forestry, Beijing, China
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Bao C, Yang Y, Ye H. Effect of Dietary Restriction on Gut Microbiota and Brain-Gut Short Neuropeptide F in Mud Crab, Scylla paramamosain. Animals (Basel) 2024; 14:2415. [PMID: 39199949 PMCID: PMC11350653 DOI: 10.3390/ani14162415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 08/13/2024] [Accepted: 08/15/2024] [Indexed: 09/01/2024] Open
Abstract
Aquatic animals frequently undergo feed deprivation and starvation stress. It is well-known that the gut microbiota and the gut-brain short neuropeptide F (sNPF) play essential roles in diet restriction. Therefore, investigating the responses of the gut microbiota and sNPF can enhance our understanding of physiological adaptations to feed deprivation and starvation stress. In this study, we examined the alterations in the gut microbiota of juvenile mud crabs under feed deprivation and starvation conditions. The results reveal differences in the richness and diversity of gut microbiota among the satisfied, half food, and starvation groups. Moreover, the microbial composition was affected by starvation stress, and more than 30 bacterial taxa exhibited significantly different abundances among the three feeding conditions. These results indicate that the diversity and composition of the gut microbiota are influenced by diet restriction, potentially involving interactions with the gut-brain sNPF. Subsequently, we detected the location of sNPF in the brains and guts of mud crabs through immunofluorescence and investigated the expression profile of sNPF under different feeding conditions. The results suggest that sNPF is located in both the brains and guts of mud crabs and shows increased expression levels among different degrees of diet restriction during a 96 h period. This study suggested a potential role for sNPF in regulating digestive activities and immunity through interactions with the gut microbiota. In conclusion, these findings significantly contribute to our understanding of the dynamic changes in gut microbiota and sNPF, highlighting their interplay in response to diet restriction.
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Affiliation(s)
- Chenchang Bao
- School of Marine Sciences, Ningbo University, Ningbo 315832, China;
| | - Yanan Yang
- School of Marine Sciences, Ningbo University, Ningbo 315832, China;
| | - Haihui Ye
- School of Fisheries, Jimei University, Xiamen 361021, China;
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Murjani K, Tripathi R, Singh V. An overview and potential of CRISPR-Cas systems for genome editing. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2024; 208:1-17. [PMID: 39266179 DOI: 10.1016/bs.pmbts.2024.07.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/14/2024]
Abstract
Genome editing involves altering of the DNA in organisms including bacteria, plants, and animals using molecular scissors that helps in treatment and diagnosis of various diseases. Genome editing technology is exponentially growing and have been developed for enabling precise genomic alterations and the addition, removal, and correction of genes. These modifications begin with the creation of double-stranded breaks (DSBs) that is generated by nucleases and can be joined through homology-directed repair (HDR) or non-homologous end-joining (NHEJ). NHEJ is quick but increases mutation chances due to deletions and insertions of nucleotides at the break site, while HDR uses homologous templates for precise repair and targeted DNA specific to the gene or sequence. Other methods such as zinc-finger protein is a transcription factor that binds with DNA and binds specific to that sequence, which uniquely recognise 3-base pairs of DNA. TALENs consists of two domains: TALE domain, a transcription activator and FokI that is a restriction endonuclease that cuts the DNA at specific sites. CRISPR-Cas systems are clustered regularly interspersed short palindromic repeats present in various bacterial species. These sequences activate RNA-guided DNA cleavage, aiding in the development of an adaptive immune defence against foreign DNA. CRISPR-Cas9 is widely used for genome editing, regulation, diagnostic and many.
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Affiliation(s)
- Karan Murjani
- Department of Biosciences, School of Science, Indrashil University, Rajpur, Mehsana, Gujarat, India
| | - Renu Tripathi
- Department of Biosciences, School of Science, Indrashil University, Rajpur, Mehsana, Gujarat, India
| | - Vijai Singh
- Department of Biosciences, School of Science, Indrashil University, Rajpur, Mehsana, Gujarat, India.
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Xia W, Zhou J, Lu Z, Li L, Zhang Y, Fan S, Krzton A, Li D. Microplastics and gut microbiomes impact on Yunnan snub-nosed monkeys in the Three Parallel Rivers region in China. Front Microbiol 2024; 15:1449522. [PMID: 39188316 PMCID: PMC11346417 DOI: 10.3389/fmicb.2024.1449522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Accepted: 07/30/2024] [Indexed: 08/28/2024] Open
Abstract
Background Microplastics (MPs) has been rapidly increasing and interacting with wildlife. As the highest altitudes inhabited non-human primate, Yunnan snub-nosed monkey (Rhinopithecus bieti) have been proven to be an umbrella and flagship species to indicate ecosystem changes and help develop environmental management strategies. In this study, we aimed to investigate the behavioral and ecological reasons for the types, content and differences of MPs in the feces of R. bieti, and explored the effects of MPs on gut microbiome of R. bieti. Methods We used the Agilent 8700 LDIR to identify the abundance and size distribution of MPs in fecal samples, and then analyzed the causes of differences in MPs content by combining data from different populations (wild group, provisioned wild group) and dominance hierarchy. At the same times, the relationships were investigated between gut microbiome diversity and MPs content. Results We first demonstrate MPs ingestion by R. bieti, which highlights the potential impacts of MPs pollution in such high-altitude, inaccessible protected areas. A total of 36 types of MPs were detected, with an average of 75.263 ± 58.141MPs/g. Food provisioning and tourism significantly increased the content of MPs in the feces of R. bieti, but tourism alone did not significantly increase the content of MPs as food provisioning. At the same time, the study found that there was no significant difference in the content of MPs between different sex groups, however, the feces MPs content of adult R. bieti was significantly lower than that of juvenile, and the social dominance hierarchies among OMUs was positively correlated with the exposure of MPs. The current level of MPs pollution did not cause gut microbiome dysbiosis of R. bieti. Conclusion Our study proved from behavioral and ecological perspectives that the R. bieti exposure to MPs was related to provisioned food, and was closely related to dominance hierarchy and age. From the perspective of intestinal microbiology, it was proved that the current intake of MPs did not cause gut microbiome dysbiosis of R. bieti. Our study provided scientific basis for formulating effective protection measures and promoting the effective protection of rare and endangered animals.
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Affiliation(s)
- Wancai Xia
- Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong, China
- Liziping Giant Panda’s Ecology and Conservation Observation and Research Station of Sichuan Province, Science and Technology Department of Sichuan Province, Chengdu, China
| | - Jiajie Zhou
- Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong, China
| | - Zhongwei Lu
- Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong, China
| | - Liang Li
- Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong, China
| | - Yuan Zhang
- Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong, China
| | - Shiyuan Fan
- Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong, China
| | - Ali Krzton
- Auburn University Libraries, Auburn University, Auburn, AL, United States
| | - Dayong Li
- Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong, China
- Liziping Giant Panda’s Ecology and Conservation Observation and Research Station of Sichuan Province, Science and Technology Department of Sichuan Province, Chengdu, China
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Shan HW, Xia XJ, Feng YL, Wu W, Li HJ, Sun ZT, Li JM, Chen JP. The plant-sucking insect selects assembly of the gut microbiota from environment to enhance host reproduction. NPJ Biofilms Microbiomes 2024; 10:64. [PMID: 39080326 PMCID: PMC11289440 DOI: 10.1038/s41522-024-00539-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 07/22/2024] [Indexed: 08/02/2024] Open
Abstract
Plant-sucking insects have intricate associations with a diverse array of microorganisms to facilitate their adaptation to specific ecological niches. The midgut of phytophagous true bugs is generally structured into four distinct compartments to accommodate their microbiota. Nevertheless, there is limited understanding regarding the origins of these gut microbiomes, the mechanisms behind microbial community assembly, and the interactions between gut microbiomes and their insect hosts. In this study, we conducted a comprehensive survey of microbial communities within the midgut compartments of a bean bug Riptortus pedestris, soybean plant, and bulk soil across 12 distinct geographical fields in China, utilizing high-throughput sequencing of the 16 S rRNA gene. Our findings illuminated that gut microbiota of the plant-sucking insects predominantly originated from the surrounding soil environment, and plants also play a subordinate role in mediating microbial acquisition for the insects. Furthermore, our investigation suggested that the composition of the insect gut microbiome was probably shaped by host selection and/or microbe-microbe interactions at the gut compartment level, with marginal influence from soil and geographical factors. Additionally, we had unveiled a noteworthy dynamic in the acquisition of core bacterial taxa, particularly Burkholderia, which were initially sourced from the environment and subsequently enriched within the insect midgut compartments. This bacterial enrichment played a significant role in enhancing insect host reproduction. These findings contribute to our evolving understanding of microbiomes within the insect-plant-soil ecosystem, shedding additional light on the intricate interactions between insects and their microbiomes that underpin the ecological significance of microbial partnerships in host adaptation.
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Affiliation(s)
- Hong-Wei Shan
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Biotechnology in Plant Protection of MARA and Zhejiang Province, Institute of Plant Virology, Ningbo University, Ningbo, 315211, China.
| | - Xie-Jiang Xia
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Biotechnology in Plant Protection of MARA and Zhejiang Province, Institute of Plant Virology, Ningbo University, Ningbo, 315211, China
| | - Yi-Lu Feng
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Biotechnology in Plant Protection of MARA and Zhejiang Province, Institute of Plant Virology, Ningbo University, Ningbo, 315211, China
| | - Wei Wu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Biotechnology in Plant Protection of MARA and Zhejiang Province, Institute of Plant Virology, Ningbo University, Ningbo, 315211, China
| | - Hong-Jie Li
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Biotechnology in Plant Protection of MARA and Zhejiang Province, Institute of Plant Virology, Ningbo University, Ningbo, 315211, China
| | - Zong-Tao Sun
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Biotechnology in Plant Protection of MARA and Zhejiang Province, Institute of Plant Virology, Ningbo University, Ningbo, 315211, China
| | - Jun-Min Li
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Biotechnology in Plant Protection of MARA and Zhejiang Province, Institute of Plant Virology, Ningbo University, Ningbo, 315211, China
| | - Jian-Ping Chen
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Biotechnology in Plant Protection of MARA and Zhejiang Province, Institute of Plant Virology, Ningbo University, Ningbo, 315211, China.
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Sha Y, Yu J, Xia D, Zhang Y, Liu J, Wang H. Remodeling of intestinal bacterial community and metabolome of Dezhou donkey induced by corn silage. Sci Rep 2024; 14:17032. [PMID: 39043883 PMCID: PMC11266621 DOI: 10.1038/s41598-024-67869-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 07/16/2024] [Indexed: 07/25/2024] Open
Abstract
Corn silage can usually improve the growth performance and the meat quality of ruminants, and subsequently increase the economic benefits of farming. However, little is known about the effects of corn silage on donkeys. This experiment investigated the effects of corn silage on the weight gain, gut microbiota and metabolites of Dezhou donkeys. A total of 24 Dezhou donkeys, sourced from the same farm and exhibiting similar age and average body weight, were utilized in this experiment. The donkeys were allocated into two groups: a control group receiving a basic diet and a test group receiving a basic diet supplemented with 30% corn silage. Each group comprised 12 donkeys, evenly distributed by sex (6 males and 6 females). The experiment lasted for 100 days. Results showed that dietary supplementation with corn silage significantly (P < 0.05) improved the weight gain of Dezhou donkeys at the end of the experiment. And the supplementation of corn silage in the diet significantly altered the bacterial community composition and metabolome in the feces of the donkeys. Notably, the relative abundance ratio of Bacteroidetes to Firmicutes was 0.76 in the control group compared to 0.96 in the test group. Furthermore, members of the Bacteroidetes and Firmicutes phyla were associated with differentiated metabolites enriched in the arachidonic acid metabolism and pentose and glucuronate interconversion pathways, both of which have been reported to be related to animal growth. Specifically, Bacteroidia exhibited statistically (P < 0.05) positive correlations with 15S-HpETE, while Bacilli demonstrated statistically (P < 0.05) negative correlations with D-Xylulose. The findings of this study can advance our mechanistic understanding of the remodeling of intestinal microbiota and metabolome induced by corn silage, as well as their relationships with the growth performance of Dezhou donkeys, which in turn favor the improvement in nutrition of Dezhou donkeys.
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Affiliation(s)
- Yujie Sha
- Shandong Key Laboratory of Biophysics, Institute of Biophysics, Dezhou University, Dezhou, 253023, China
- International Joint Laboratory of Agricultural Food Science and Technology of Universities of Shandong, Dezhou University, Dezhou, 253023, China
| | - Jiafeng Yu
- Shandong Key Laboratory of Biophysics, Institute of Biophysics, Dezhou University, Dezhou, 253023, China.
- International Joint Laboratory of Agricultural Food Science and Technology of Universities of Shandong, Dezhou University, Dezhou, 253023, China.
| | - Dong Xia
- Dezhou Animal Husbandry and Veterinary Career Development Center (Dezhou Animal Disease Prevention and Control Center), Dezhou, 253023, China
| | - Yan Zhang
- Institute of Crop Germplasm Resources, Shandong Academy of Agriculture Sciences, Jinan, 250100, China
| | - Jian Liu
- Shandong Key Laboratory of Biophysics, Institute of Biophysics, Dezhou University, Dezhou, 253023, China
- International Joint Laboratory of Agricultural Food Science and Technology of Universities of Shandong, Dezhou University, Dezhou, 253023, China
| | - Huisong Wang
- International Joint Laboratory of Agricultural Food Science and Technology of Universities of Shandong, Dezhou University, Dezhou, 253023, China
- Belgorod College of Food Sciences, Dezhou University, Dezhou, 253023, China
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Zhou H, Ye P, Xiong W, Duan X, Jing S, He Y, Zeng Z, Wei Y, Ye Q. Genome-scale CRISPR-Cas9 screening in stem cells: theories, applications and challenges. Stem Cell Res Ther 2024; 15:218. [PMID: 39026343 PMCID: PMC11264826 DOI: 10.1186/s13287-024-03831-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 07/02/2024] [Indexed: 07/20/2024] Open
Abstract
Due to the rapid development of stem cell technology, there have been tremendous advances in molecular biological and pathological research, cell therapy as well as organoid technologies over the past decades. Advances in genome editing technology, particularly the discovery of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-related protein 9 (Cas9), have further facilitated the rapid development of stem cell researches. The CRISPR-Cas9 technology now goes beyond creating single gene editing to enable the inhibition or activation of endogenous gene loci by fusing inhibitory (CRISPRi) or activating (CRISPRa) domains with deactivated Cas9 proteins (dCas9). These tools have been utilized in genome-scale CRISPRi/a screen to recognize hereditary modifiers that are synergistic or opposing to malady mutations in an orderly and fair manner, thereby identifying illness mechanisms and discovering novel restorative targets to accelerate medicinal discovery investigation. However, the application of this technique is still relatively rare in stem cell research. There are numerous specialized challenges in applying large-scale useful genomics approaches to differentiated stem cell populations. Here, we present the first comprehensive review on CRISPR-based functional genomics screening in the field of stem cells, as well as practical considerations implemented in a range of scenarios, and exploration of the insights of CRISPR-based screen into cell fates, disease mechanisms and cell treatments in stem cell models. This review will broadly benefit scientists, engineers and medical practitioners in the areas of stem cell research.
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Affiliation(s)
- Heng Zhou
- Center of Regenerative Medicine and Department of Stomatology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China
| | - Peng Ye
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China
| | - Wei Xiong
- Center of Regenerative Medicine and Department of Stomatology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China
| | - Xingxiang Duan
- Center of Regenerative Medicine and Department of Stomatology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China
| | - Shuili Jing
- Center of Regenerative Medicine and Department of Stomatology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China
| | - Yan He
- Institute of Regenerative and Translational Medicine, Tianyou Hospital of Wuhan University of Science and Technology, Wuhan, 430064, Hubei, People's Republic of China
- Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
| | - Zhi Zeng
- Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.
| | - Yen Wei
- The Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, People's Republic of China.
| | - Qingsong Ye
- Center of Regenerative Medicine and Department of Stomatology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.
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Qu P, Wang B, Qi M, Lin R, Chen H, Xie C, Zhang Z, Qiu J, Du H, Ge Y. Medicinal Plant Root Exudate Metabolites Shape the Rhizosphere Microbiota. Int J Mol Sci 2024; 25:7786. [PMID: 39063028 PMCID: PMC11277521 DOI: 10.3390/ijms25147786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 07/11/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
The interactions between plants and rhizosphere microbes mediated by plant root exudates are increasingly being investigated. The root-derived metabolites of medicinal plants are relatively diverse and have unique characteristics. However, whether medicinal plants influence their rhizosphere microbial community remains unknown. How medicinal plant species drive rhizosphere microbial community changes should be clarified. In this study involving high-throughput sequencing of rhizosphere microbes and an analysis of root exudates using a gas chromatograph coupled with a time-of-flight mass spectrometer, we revealed that the root exudate metabolites and microorganisms differed among the rhizosphere soils of five medicinal plants. Moreover, the results of a correlation analysis indicated that bacterial and fungal profiles in the rhizosphere soils of the five medicinal plants were extremely significantly or significantly affected by 10 root-associated metabolites. Furthermore, among the 10 root exudate metabolites, two (carvone and zymosterol) had opposite effects on rhizosphere bacteria and fungi. Our study findings suggest that plant-derived exudates modulate changes to rhizosphere microbial communities.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Huabo Du
- College of Tropical Crops, Yunnan Agricultural University, Pu’er 665099, China; (P.Q.); (B.W.); (M.Q.); (R.L.); (H.C.); (C.X.); (Z.Z.); (J.Q.)
| | - Yu Ge
- College of Tropical Crops, Yunnan Agricultural University, Pu’er 665099, China; (P.Q.); (B.W.); (M.Q.); (R.L.); (H.C.); (C.X.); (Z.Z.); (J.Q.)
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Teles D, Fine BM. Using induced pluripotent stem cells for drug discovery in arrhythmias. Expert Opin Drug Discov 2024; 19:827-840. [PMID: 38825838 PMCID: PMC11227103 DOI: 10.1080/17460441.2024.2360420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 05/23/2024] [Indexed: 06/04/2024]
Abstract
INTRODUCTION Arrhythmias are disturbances in the normal rhythm of the heart and account for significant cardiovascular morbidity and mortality worldwide. Historically, preclinical research has been anchored in animal models, though physiological differences between these models and humans have limited their clinical translation. The discovery of human induced pluripotent stem cells (iPSC) and subsequent differentiation into cardiomyocyte has led to the development of new in vitro models of arrhythmias with the hope of a new pathway for both exploration of pathogenic variants and novel therapeutic discovery. AREAS COVERED The authors describe the latest two-dimensional in vitro models of arrhythmias, several examples of the use of these models in drug development, and the role of gene editing when modeling diseases. They conclude by discussing the use of three-dimensional models in the study of arrythmias and the integration of computational technologies and machine learning with experimental technologies. EXPERT OPINION Human iPSC-derived cardiomyocytes models have significant potential to augment disease modeling, drug discovery, and toxicity studies in preclinical development. While there is initial success with modeling arrhythmias, the field is still in its nascency and requires advances in maturation, cellular diversity, and readouts to emulate arrhythmias more accurately.
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Affiliation(s)
- Diogo Teles
- Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
| | - Barry M. Fine
- Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA
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Mei YX, Yang K, Zhang L, Jin Y, Yang N, Yang H, Zheng YL, Pang YS, Gong YJ, Zhou H, Zuo YL, Ding WJ. Dysrhythmic saliva microbiota in mobile phone addicts with sleep disorders and restored by acupuncture. Front Psychiatry 2024; 15:1335554. [PMID: 38957739 PMCID: PMC11217316 DOI: 10.3389/fpsyt.2024.1335554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 05/27/2024] [Indexed: 07/04/2024] Open
Abstract
Background Mobile phone addiction (MPA) greatly affects the biological clock and sleep quality and is emerging as a behavioral disorder. The saliva microbiota has been linked to circadian rhythms, and our previous research revealed dysrhythmic saliva metabolites in MPA subjects with sleep disorders (MPASD). In addition, acupuncture had positive effects. However, the dysbiotic saliva microbiota in MPASD patients and the restorative effects of acupuncture are unclear. Objectives To probe the circadian dysrhythmic characteristics of the saliva microbiota and acupunctural restoration in MPASD patients. Methods MPASD patients and healthy volunteers were recruited by the Mobile Phone Addiction Tendency Scale (MPATS) and the Pittsburgh Sleep Quality Index (PSQI). Saliva samples were collected every 4 h for 72 h. After saliva sampling, six MPDSD subjects (group M) were acupuncturally treated (group T), and subsequent saliva sampling was conducted posttreatment. Finally, all the samples were subjected to 16S rRNA gene sequencing and bioinformatic analysis. Results Significantly increased MPATS and PSQI scores were observed in MPDSD patients (p< 0.01), but these scores decreased (p<0.001) after acupuncture intervention. Compared with those in healthy controls, the diversity and structure of the saliva microbiota in MPASD patients were markedly disrupted. Six genera with circadian rhythms were detected in all groups, including Sulfurovum, Peptostreptococcus, Porphyromonas and Prevotella. There were five genera with circadian rhythmicity in healthy people, of which the rhythmicities of the genera Rothia and Lautropia disappeared in MPASD patients but effectively resumed after acupuncture intervention. Conclusions This work revealed dysrhythmic salivary microbes in MPASD patients, and acupuncture, as a potential intervention, could be effective in mitigating this ever-rising behavioral epidemic.
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Affiliation(s)
- Ying-Xiu Mei
- Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Kun Yang
- Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Lu Zhang
- Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yue Jin
- Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ni Yang
- Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hong Yang
- Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ya-Li Zheng
- Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yue-Shan Pang
- Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- The Second Clinical Medical College of North Sichuan Medical College, Nanchong, China
| | - Yan-Ju Gong
- Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hang Zhou
- Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yu-Lin Zuo
- Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wei-Jun Ding
- Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Liu SH, Zhang Y, Guo ZX, Ayaz S, Wang YX, Huang ZH, Cao HH, Xu JP. Effects of baculovirus infection on intestinal microflora of BmNPV resistant and susceptible strain silkworm. JOURNAL OF ECONOMIC ENTOMOLOGY 2024; 117:1141-1151. [PMID: 38706118 DOI: 10.1093/jee/toae088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 03/05/2024] [Accepted: 04/13/2024] [Indexed: 05/07/2024]
Abstract
Bombyx mori L. (Lepidoptera: Bombycidae) nucleopolyhedrovirus (BmNPV) is a serious pathogen causing huge economic losses to sericulture. There is growing evidence that the gut microbiota of silkworms plays a critical role in shaping host responses and interactions with viral infection. However, little is known about the differences in the composition and diversity of intestinal microflora, especially with respect to silkworm strain differences and BmNPV infection-induced changes. Here, we aim to explore the differences between BmNPV-resistant strain A35 and susceptible strain P50 silkworm and the impact of BmNPV infection on intestinal microflora in different strains. The 16S rDNA sequencing analysis revealed that the fecal microbial populations were distinct between A35 and P50 and were significantly changed post BmNPV infection in both strains. Further analysis showed that the BmNPV-resistant strain silkworm possessed higher bacterial diversity than the susceptible strain, and BmNPV infection reduced the diversity of intestinal flora assessed by feces in both silkworm strains. In response to BmNPV infection, the abundance of Muribaculaceae increased in P50 and decreased in A35, while the abundance of Enterobacteriaceae decreased in P50 and increased in A35. These results indicated that BmNPV infection had various effects on the abundance of fecal microflora in different silkworm strains. Our findings not only broadened the understanding of host-pathogen interactions but also provided theoretical help for the breeding of resistant strains and healthy rearing of silkworms based on symbiotic bacteria.
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Affiliation(s)
- Shi-Huo Liu
- Anhui Province Key Laboratory of Resource Insects Biology and Innovative Utilization, School of Life Sciences, Anhui Agricultural University, Hefei 230036, China
- Anhui International Joint Research and Developmental Center of Sericulture Resources Utilization, Hefei 230036, China
| | - Ying Zhang
- Anhui Province Key Laboratory of Resource Insects Biology and Innovative Utilization, School of Life Sciences, Anhui Agricultural University, Hefei 230036, China
- Anhui International Joint Research and Developmental Center of Sericulture Resources Utilization, Hefei 230036, China
| | - Zhe-Xiao Guo
- Anhui Province Key Laboratory of Resource Insects Biology and Innovative Utilization, School of Life Sciences, Anhui Agricultural University, Hefei 230036, China
- Anhui International Joint Research and Developmental Center of Sericulture Resources Utilization, Hefei 230036, China
| | - Sadaf Ayaz
- Anhui Province Key Laboratory of Resource Insects Biology and Innovative Utilization, School of Life Sciences, Anhui Agricultural University, Hefei 230036, China
- Anhui International Joint Research and Developmental Center of Sericulture Resources Utilization, Hefei 230036, China
| | - Yan-Xiang Wang
- Anhui Province Key Laboratory of Resource Insects Biology and Innovative Utilization, School of Life Sciences, Anhui Agricultural University, Hefei 230036, China
- Anhui International Joint Research and Developmental Center of Sericulture Resources Utilization, Hefei 230036, China
| | - Zhi-Hao Huang
- Anhui Province Key Laboratory of Resource Insects Biology and Innovative Utilization, School of Life Sciences, Anhui Agricultural University, Hefei 230036, China
- Anhui International Joint Research and Developmental Center of Sericulture Resources Utilization, Hefei 230036, China
| | - Hui-Hua Cao
- Anhui Province Key Laboratory of Resource Insects Biology and Innovative Utilization, School of Life Sciences, Anhui Agricultural University, Hefei 230036, China
- Anhui International Joint Research and Developmental Center of Sericulture Resources Utilization, Hefei 230036, China
| | - Jia-Ping Xu
- Anhui Province Key Laboratory of Resource Insects Biology and Innovative Utilization, School of Life Sciences, Anhui Agricultural University, Hefei 230036, China
- Anhui International Joint Research and Developmental Center of Sericulture Resources Utilization, Hefei 230036, China
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Chen Y, Chen Y, Li Y, Du E, Sun Z, Lu Z, Gui F. Comparative study of the gut microbial community structure of Spodoptera frugiperda and Spodoptera literal (Lepidoptera). PeerJ 2024; 12:e17450. [PMID: 38860210 PMCID: PMC11164061 DOI: 10.7717/peerj.17450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 05/03/2024] [Indexed: 06/12/2024] Open
Abstract
Background Spodoptera frugiperda, the fall armyworm is a destructive invasive pest, and S. litura the tobacco cutworm, is a native species closely related to S. frugiperda. The gut microbiota plays a vital role in insect growth, development, metabolism and immune system. Research on the competition between invasive species and closely related native species has focused on differences in the adaptability of insects to the environment. Little is known about gut symbiotic microbe composition and its role in influencing competitive differences between these two insects. Methods We used a culture-independent approach targeting the 16S rRNA gene of gut bacteria of 5th instar larvae of S. frugiperda and S. litura. Larvae were reared continuously on maize leaves for five generations. We analyzed the composition, abundance, diversity, and metabolic function of gut microbiomes of S. frugiperda and S. litura larvae. Results Firmicutes, Proteobacteria, and Bacteroidetes were the dominant bacterial phyla in both species. Enterococcus, ZOR0006, Escherichia, Bacteroides, and Lactobacillus were the genera with the highest abundance in S. frugiperda. Enterococcus, Erysipelatoclostridium, ZOR0006, Enterobacter, and Bacteroides had the highest abundance in S. litura. According to α-diversity analysis, the gut bacterial diversity of S. frugiperda was significantly higher than that of S. litura. KEGG analysis showed 15 significant differences in metabolic pathways between S. frugiperda and S. litura gut bacteria, including transcription, cell growth and death, excretory system and circulatory system pathways. Conclusion In the same habitat, the larvae of S. frugiperda and S. litura showed significant differences in gut bacterial diversity and community composition. Regarding the composition and function of gut bacteria, the invasive species S. frugiperda may have a competitive advantage over S. litura. This study provides a foundation for developing control strategies for S. frugiperda and S. litura.
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Affiliation(s)
- Yaping Chen
- College of Plant Protection, Yunnan Agricutural University, Kunming, Yunnan, China
| | - Yao Chen
- College of Plant Protection, Yunnan Agricutural University, Kunming, Yunnan, China
| | - Yahong Li
- Yunnan Plant Protection and Quarantine Station, Kunming, Yunnan, China
| | - Ewei Du
- College of Plant Protection, Yunnan Agricutural University, Kunming, Yunnan, China
| | - Zhongxiang Sun
- College of Plant Protection, Yunnan Agricutural University, Kunming, Yunnan, China
| | - Zhihui Lu
- College of Plant Protection, Yunnan Agricutural University, Kunming, Yunnan, China
| | - Furong Gui
- College of Plant Protection, Yunnan Agricutural University, Kunming, Yunnan, China
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Bisht D, Salave S, Desai N, Gogoi P, Rana D, Biswal P, Sarma G, Benival D, Kommineni N, Desai D. Genome editing and its role in vaccine, diagnosis, and therapeutic advancement. Int J Biol Macromol 2024; 269:131802. [PMID: 38670178 DOI: 10.1016/j.ijbiomac.2024.131802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 02/25/2024] [Accepted: 03/15/2024] [Indexed: 04/28/2024]
Abstract
Genome editing involves precise modification of specific nucleotides in the genome using nucleases like CRISPR/Cas, ZFN, or TALEN, leading to increased efficiency of homologous recombination (HR) for gene editing, and it can result in gene disruption events via non-homologous end joining (NHEJ) or homology-driven repair (HDR). Genome editing, particularly CRISPR-Cas9, revolutionizes vaccine development by enabling precise modifications of pathogen genomes, leading to enhanced vaccine efficacy and safety. It allows for tailored antigen optimization, improved vector design, and deeper insights into host genes' impact on vaccine responses, ultimately enhancing vaccine development and manufacturing processes. This review highlights different types of genome editing methods, their associated risks, approaches to overcome the shortcomings, and the diverse roles of genome editing.
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Affiliation(s)
- Deepanker Bisht
- ICAR- Indian Veterinary Research Institute, Izatnagar 243122, Bareilly, India
| | - Sagar Salave
- National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad 382355, Gujarat, India
| | - Nimeet Desai
- Indian Institute of Technology Hyderabad, Kandi 502285, Telangana, India
| | - Purnima Gogoi
- School of Medicine and Public Health, University of Wisconsin and Madison, Madison, WI 53726, USA
| | - Dhwani Rana
- National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad 382355, Gujarat, India
| | - Prachurya Biswal
- College of Veterinary and Animal Sciences, Bihar Animal Sciences University, Kishanganj 855115, Bihar, India
| | - Gautami Sarma
- College of Veterinary & Animal Sciences, G. B. Pant University of Agriculture and Technology, Pantnagar 263145, U.S. Nagar, Uttarakhand, India
| | - Derajram Benival
- National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad 382355, Gujarat, India.
| | | | - Dhruv Desai
- School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
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Zhang Y, Zhang J, Liu Y, Ren S, Tao N, Meng F, Cao Q, Liu R. High fat diet increases the severity of collagen-induced arthritis in mice by altering the gut microbial community. Adv Rheumatol 2024; 64:44. [PMID: 38816873 DOI: 10.1186/s42358-024-00382-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 05/06/2024] [Indexed: 06/01/2024] Open
Abstract
OBJECTIVES Research has demonstrated that obesity may be associated with rheumatoid arthritis (RA). In addition, gut microbiota and its metabolites contribute to the occurrence and development of RA and obesity. However, the mechanism by which obesity affects RA remains unclear. In this study, we aimed to investigate whether gut microbiota and their metabolites alter the effects of high fat diet (HFD) on the severity of collagen-induced arthritis (CIA) in mice. METHODS Briefly, mice were divided into normal group (N), CIA model group (C), HFD group (T), and HFD CIA group (CT). Hematoxylin and Eosin staining(HE) and Safranin O-fast green staining were conducted, and levels of blood lipid and inflammatory cytokines were measured. 16S rDNA sequencing technique and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics were performed to explore changes in the microbiota structure to further reveal the pathomechanism of HFD on CIA. RESULTS HFD aggravated the severity of CIA in mice. The CT group had the highest proportion of microbial abundance of Blautia, Oscillibacter, Ruminiclostridium-9, and Lachnospiraceae UCG 006 at the genus level, but had a lower proportion of Alistipes. Additionally, the fecal metabolic phenotype of the combined CT group shows significant changes, with differential metabolites enriched in 9 metabolic pathways, including primary bile acid biosynthesis, arginine biosynthesis, sphingolipid metabolism, purine metabolism, linoleic acid metabolism, oxytocin signaling pathway, aminoacyl-tRNA biosynthesis, the pentose phosphate pathway, and sphingolipid signaling pathway. Correlation analysis revealed that some of the altered gut microbiota genera were strongly correlated with changes in fecal metabolites, total cholesterol (TC), triglyceride (TG), and inflammatory cytokine levels. CONCLUSIONS This study shows that HFD may aggravate inflammatory reaction in CIA mice by altering the gut microbiota and metabolic pathways.
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Affiliation(s)
- Yang Zhang
- The First Hospital of China Medical University, Shenyang, 110002, Liaoning, China
| | - Jie Zhang
- The First Hospital of China Medical University, Shenyang, 110002, Liaoning, China
| | - Yantong Liu
- The First Hospital of China Medical University, Shenyang, 110002, Liaoning, China
| | - Shuang Ren
- The First Hospital of China Medical University, Shenyang, 110002, Liaoning, China
| | - Ning Tao
- The First Hospital of China Medical University, Shenyang, 110002, Liaoning, China
| | - Fanyan Meng
- The First Hospital of China Medical University, Shenyang, 110002, Liaoning, China
| | - Qi Cao
- Liaoning University of Traditional Chinese Medicine, Shenyang, 110001, Liaoning, China
| | - Ruoshi Liu
- The First Hospital of China Medical University, Shenyang, 110002, Liaoning, China.
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Yan Y, Zheng X, Liu G, Shi G, Li C, Chen H, He X, Lin K, Deng Z, Zhang H, Li WG, Chen H, Tong X, Zhu Z. Gut microbiota-derived cholic acid mediates neonatal brain immaturity and white matter injury under chronic hypoxia. iScience 2024; 27:109633. [PMID: 38638560 PMCID: PMC11025012 DOI: 10.1016/j.isci.2024.109633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 02/18/2024] [Accepted: 03/26/2024] [Indexed: 04/20/2024] Open
Abstract
Chronic hypoxia, common in neonates, disrupts gut microbiota balance, which is crucial for brain development. This study utilized cyanotic congenital heart disease (CCHD) patients and a neonatal hypoxic rat model to explore the association. Both hypoxic rats and CCHD infants exhibited brain immaturity, white matter injury (WMI), brain inflammation, and motor/learning deficits. Through 16s rRNA sequencing and metabolomic analysis, a reduction in B. thetaiotaomicron and P. distasonis was identified, leading to cholic acid accumulation. This accumulation triggered M1 microglial activation and inflammation-induced WMI. Administration of these bacteria rescued cholic acid-induced WMI in hypoxic rats. These findings suggest that gut microbiota-derived cholic acid mediates neonatal WMI and brain inflammation, contributing to brain immaturity under chronic hypoxia. Therapeutic targeting of these bacteria provides a non-invasive intervention for chronic hypoxia patients.
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Affiliation(s)
- Yichen Yan
- Department of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Center for Brain Science, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoli Zheng
- Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Center for Brain Science, Shanghai Children’s Medical Center, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Gang Liu
- Department of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Guocheng Shi
- Department of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Cong Li
- Department of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongtong Chen
- Department of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaomin He
- Department of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kana Lin
- Center for Brain Science, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Pharmacy, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhaohui Deng
- Department of Gastroenterology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hao Zhang
- Department of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei-Guang Li
- Center for Brain Science, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huiwen Chen
- Department of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoping Tong
- Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Center for Brain Science, Shanghai Children’s Medical Center, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhongqun Zhu
- Department of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Center for Brain Science, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Jiang N, Chang X, Huang W, Khan FU, Fang JKH, Hu M, Xu EG, Wang Y. Physiological response of mussel to rayon microfibers and PCB's exposure: Overlooked semi-synthetic micropollutant? JOURNAL OF HAZARDOUS MATERIALS 2024; 470:134107. [PMID: 38554520 DOI: 10.1016/j.jhazmat.2024.134107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 03/08/2024] [Accepted: 03/20/2024] [Indexed: 04/01/2024]
Abstract
Rayon microfibers, micro-sized semi-synthetic polymers derived from cellulose, have been frequently detected and reported as "micropollutants" in marine environments. However, there has been limited research on their ecotoxicity and combined effects with persistent organic pollutants (POPs). To address these knowledge gaps, thick-shell mussels (Mytilus coruscus) were exposed to rayon microfibers at 1000 pieces/L, along with polychlorinated biphenyls (PCBs) at 100 and 1000 ng/L for 14 days, followed by a 7-day recovery period. We found that rayon microfibers at the environmentally relevant concentration exacerbated the irreversible effects of PCBs on the immune and digestive systems of mussels, indicating chronic and sublethal impacts. Furthermore, the results of 16 s rRNA sequencing demonstrated significant effects on the community structure, species richness, and diversity of the mussels' intestinal microbiota. The branching map analysis identified the responsive bacteria to rayon microfibers and PCBs belonging to the Proteobacteria, Actinobacteriota, and Bacteroidota phyla. Despite not being considered a conventional plastic, the extensive and increasing use of rayon fibers, their direct toxicological effects, and their interaction with POPs highlight the need for urgent attention, investigation, and regulation to address their contribution to "micropollution".
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Affiliation(s)
- Ningjin Jiang
- International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology, Shanghai Ocean University, Shanghai 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai 201306, China
| | - Xueqing Chang
- International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology, Shanghai Ocean University, Shanghai 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai 201306, China
| | - Wei Huang
- Key Laboratory of Marine Ecosystem Dynamics, Second Institute of Oceanography, Ministry of Natural Resources, Hangzhou 310012, China
| | - Fahim Ullah Khan
- International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology, Shanghai Ocean University, Shanghai 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai 201306, China
| | - James Kar-Hei Fang
- Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Hong Kong Special Administrative Region of China; State Key Laboratory of Marine Pollution, City University of Hong Kong, Kowloon Tong, Hong Kong Special Administrative Region of China
| | - Menghong Hu
- International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology, Shanghai Ocean University, Shanghai 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai 201306, China
| | - Elvis Genbo Xu
- Department of Biology, University of Southern Denmark, Odense, Denmark.
| | - Youji Wang
- International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology, Shanghai Ocean University, Shanghai 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai 201306, China.
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Castillo SR, Simone BW, Clark KJ, Devaux P, Ekker SC. Unconstrained Precision Mitochondrial Genome Editing with αDdCBEs. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.05.13.593977. [PMID: 38798498 PMCID: PMC11118498 DOI: 10.1101/2024.05.13.593977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2024]
Abstract
DddA-derived cytosine base editors (DdCBEs) enable the targeted introduction of C•G-to-T•A conversions in mitochondrial DNA (mtDNA). DdCBEs are often deployed as pairs, with each arm comprised of a transcription activator-like effector (TALE), a split double-stranded DNA deaminase half, and a uracil glycosylase inhibitor. This pioneering technology has helped improve our understanding of cellular processes involving mtDNA and has paved the way for the development of models and therapies for genetic disorders caused by pathogenic mtDNA variants. Nonetheless, given the intrinsic properties of TALE proteins, several target sites in human mtDNA remain out of reach to DdCBEs and other TALE-based technologies. Specifically, due to the conventional requirement for a thymine immediately upstream of the TALE target sequences (i.e., the 5'-T constraint), over 150 loci in the human mitochondrial genome are presumed to be inaccessible to DdCBEs. Previous attempts at circumventing this constraint, either by developing monomeric DdCBEs or utilizing DNA-binding domains alternative to TALEs, have resulted in suboptimal specificity profiles with reduced therapeutic potential. Here, aiming to challenge and elucidate the relevance of the 5'-T constraint in the context of DdCBE-mediated mtDNA editing, and to expand the range of motifs that are editable by this technology, we generated αDdCBEs that contain modified TALE proteins engineered to recognize all 5' bases. Notably, 5'-T-noncompliant, canonical DdCBEs efficiently edited mtDNA at diverse loci. However, DdCBEs were frequently outperformed by αDdCBEs, which consistently displayed significant improvements in activity and specificity, regardless of the 5'-most bases of their TALE binding sites. Furthermore, we showed that αDdCBEs are compatible with DddA tox and its derivatives DddA6, and DddA11, and we validated TALE shifting with αDdCBEs as an effective approach to optimize base editing outcomes at a single target site. Overall, αDdCBEs enable efficient, specific, and unconstrained mitochondrial base editing.
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