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Shi J, Zhao F, Qiu T, Ren D, Li Z, Ma J, Zhao J. High-altitude hypoxia exacerbates chemotherapy-induced myelosuppression by lowering serum G-CSF/GM-CSF and regulating apoptosis and proliferation. Discov Oncol 2025; 16:938. [PMID: 40434597 DOI: 10.1007/s12672-025-02611-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Accepted: 05/07/2025] [Indexed: 05/29/2025] Open
Abstract
The unique hypoxic environment in high-altitude regions is increasingly drawing attention for its impact on the health of residents, particularly in patients post-chemotherapy. This study aimed to investigate the effects and potential mechanisms of high-altitude hypoxia on myelosuppression following chemotherapy, with the goal of providing a theoretical basis for clinical treatment. A retrospective clinical study of 80 patients with breast cancer revealed that patients in the plateau exhibited a significantly higher incidence of grade 3 or higher neutropenia and any level of neutropenia post-chemotherapy than those in the plain, with propensity score matching (PSM) confirming these associations. Animal experiments revealed that high-altitude hypoxia reduced the white blood cell (WBC) count, granulocyte count, lymphocyte count, and number of bone marrow nucleated cells (BMNCs) in cyclophosphamide (CTX)-treated mice. Additionally, high-altitude hypoxia induced a significant reduction in the proliferation index and an elevation in apoptosis rates in BMNCs. High-altitude hypoxia also significantly reduced serum levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Transcriptomic analysis of BMNCs demonstrated that high-altitude hypoxia might modulate the hematopoietic function in CTX-induced myelosuppression mice through pathways related to hematopoiesis, such as porphyrin metabolism, hematopoietic cell lineage, ECM-receptor interaction, and PI3K-Akt signaling pathway. Our results suggest that high-altitude hypoxia exacerbates chemotherapy-induced myelosuppression, possibly through reducing the serum level of G-CSF/GM-CSF and regulating apoptosis and proliferation by PI3K-Akt signaling pathway, highlighting that cancer patients undergoing chemotherapy in hypoxic environments may require enhanced supportive care to mitigate these adverse effects.
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Affiliation(s)
- Jing Shi
- School of Clinical Medicine of Qinghai University, Affiliated Hospital of Qinghai University, Xining, 810000, China
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
- Affiliated Hospital of Jining Medical University, Jining, 272029, Shandong, China
| | - Fuxing Zhao
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Tianlei Qiu
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Dengfeng Ren
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Zitao Li
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Junli Ma
- Affiliated Hospital of Jining Medical University, Jining, 272029, Shandong, China
| | - Jiuda Zhao
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China.
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Chen SH, Ke TL, Shih CH, Hsiung CN, Chen KC, Huang ZX, Chuang TH, Chen LK, Chen L. Reduced Taurine Synthesis Underlies Morphine-Promoted Lung Metastasis of Triple-Negative Breast Cancer. Cancers (Basel) 2025; 17:1086. [PMID: 40227606 PMCID: PMC11988058 DOI: 10.3390/cancers17071086] [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: 01/31/2025] [Revised: 03/17/2025] [Accepted: 03/19/2025] [Indexed: 04/15/2025] Open
Abstract
Background: The mechanisms underlying the progression and metastasis of triple-negative breast cancer (TNBC) in the context of extended morphine exposure remain poorly understood. Morphine consumption has been a pressing issue in many countries. While the physiological impact of extended morphine use is multifaceted, cancer patients with a history of extended morphine usage often have a poor prognosis. Methods: In this study, we investigated the impact of extended morphine treatment on the transcriptional profiles of TNBC. To this end, mice were administered morphine intraperitoneally for 14 days, followed by the implantation of EO771 cells, which are triple-negative breast cancer cells, into their mammary fat pad. After primary tumors were removed on the 38th day, a subset of mice was continuously given saline or morphine until the 68th day. Tumor size, organ metastasis, and tumor RNA expression were analyzed. Results: Our findings showed that extended exposure to morphine led to an increase in lung metastasis in the mouse model of triple-negative breast cancer. We analyzed RNA sequencing on tumors to compare their transcriptional profiles with or without metastasis. Through pathway analysis, we specifically examined the novel impact of morphine on the downregulation of taurine/hypotaurine biosynthesis. Given that morphine, droperidol (a dopamine receptor antagonist), and naloxone (an opioid receptor antagonist) might act through either opioid receptors or dopamine receptors, we further demonstrated that taurine mitigated EO771 cell invasion induced by morphine but not by droperidol or naloxone treatment. Additionally, morphine treatment markedly decreased the expression of GAD1, one of the enzymes essential for taurine biosynthesis, whereas droperidol and naloxone did not. Conclusions: The findings of morphine-induced reduction in GAD1 levels and the inhibition of invasion by taurine treatment suggest that taurine could serve as a potential supplement for triple-negative breast cancer patients who require morphine as part of their treatment regimen or due to their circumstances.
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Affiliation(s)
- Shih-Hong Chen
- Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 300044, Taiwan; (S.-H.C.); (T.-L.K.)
- Department of Anesthesiology, Cathay General Hospital Medical Center, Taipei City 106438, Taiwan
| | - Ting-Ling Ke
- Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 300044, Taiwan; (S.-H.C.); (T.-L.K.)
| | - Chien-Hung Shih
- Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 300044, Taiwan; (S.-H.C.); (T.-L.K.)
| | - Chia-Ni Hsiung
- Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 300044, Taiwan; (S.-H.C.); (T.-L.K.)
| | - Kuo-Chin Chen
- Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 300044, Taiwan; (S.-H.C.); (T.-L.K.)
| | - Zi-Xuan Huang
- Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 300044, Taiwan; (S.-H.C.); (T.-L.K.)
| | - Tsung-Hsien Chuang
- Immunology Research Center, National Health Research Institutes, Miaoli City 350401, Taiwan
| | - Li-Kuei Chen
- College of Medicine, China Medical University, Taichung City 406040, Taiwan
- Department of Anesthesiology, China Medical University Hospital, Taichung City 404327, Taiwan
| | - Linyi Chen
- Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 300044, Taiwan; (S.-H.C.); (T.-L.K.)
- Department of Medical Science, National Tsing Hua University, Hsinchu 300044, Taiwan
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Kaur R, Kaushik D, Bansal V, Sharma A, Kumar M. Unrevealing the potential of macroalgae Porphyra sp. (nori) in food, pharmaceutics and health sector. J Food Sci 2025; 90:e70110. [PMID: 40111034 DOI: 10.1111/1750-3841.70110] [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: 01/15/2025] [Revised: 02/15/2025] [Accepted: 02/18/2025] [Indexed: 03/22/2025]
Abstract
Porphyra sp. (nori), a species of red seaweed, has garnered attention for its rich nutritional profile and diverse bioactive compounds. This review synthesizes current research on Porphyra nori, focusing on its composition, bioactive components, health benefits, and potential applications in functional foods and therapeutics. Key bioactives identified include polysaccharides, peptides, phenolics, and vitamins, each contributing to antioxidant, anti-inflammatory, and anticancer properties and also modulating the immune responses, supporting cardiovascular health, and influencing metabolic pathways. Furthermore, it serves as a valuable source of vitamin B12 and plays a crucial function in the synthesis of DNA, the generation of red blood cells, and the cognitive development of the neurological system. It reduces dependence on animal-derived sources for vitamin B12, whereas innovations in cultivation and processing methods significantly improve its absorption and market potential. Future research directions include elucidating molecular mechanisms, optimizing extraction methods, and exploring synergistic effects with other foods or pharmaceuticals. Porphyra nori emerges as a promising source of bioactive compounds, poised to contribute to personalized nutrition and preventive healthcare strategies.
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Affiliation(s)
- Rajdeep Kaur
- Department of Food Technology and Nutrition, Lovely Professional University, Phagwara, Punjab, India
| | - Deepika Kaushik
- Department of Biotechnology, Faculty of Applied Sciences and Biotechnology, Shoolini University, Solan, Himachal Pradesh, India
| | - Vikas Bansal
- Department of Food Technology, School of Engineering and Technology, Jaipur National University, Jaipur, Rajasthan, India
| | - Avinash Sharma
- Department of Biotechnology, Graphic Era (deemed to be University), Dehradun, Uttarakhand, India
| | - Mukul Kumar
- Department of Food Technology and Nutrition, Lovely Professional University, Phagwara, Punjab, India
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Zhou X, Yang Y, Qiu X, Deng H, Cao H, Liao T, Chen X, Huang C, Lin D, Ni G. Antioxidant taurine inhibits chondrocyte ferroptosis through upregulation of OGT/Gpx4 signaling in osteoarthritis induced by anterior cruciate ligament transection. J Adv Res 2025:S2090-1232(25)00029-3. [PMID: 39778769 DOI: 10.1016/j.jare.2025.01.010] [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: 11/13/2024] [Revised: 01/04/2025] [Accepted: 01/04/2025] [Indexed: 01/11/2025] Open
Abstract
OBJECTIVE The aim of this study was to investigate the potential molecular mechanisms by which taurine protects against cartilage degeneration. METHODS The anterior cruciate ligament transection (ACLT) surgery was used to construct an animal model of osteoarthritis (OA). Metabolomics was used to identify characteristic metabolites in osteoarthritic chondrocytes. Transcriptomics and metabolomics were used to explore potential mechanisms by which the small molecule metabolite taurine protects against inflammatory chondrocyte damage. Cell transfection and small molecule inhibitors/agonists were used to validate the molecular mechanisms by which taurine protects inflammatory chondrocytes in vitro. Finally, adeno-associated virus and small molecule inhibitors/agonists were used to validate the molecular mechanisms by which taurine protects against cartilage degeneration in vivo. RESULTS Metabolomic assays identified taurine as a possible key metabolic molecule in the progression of OA. Transcriptomics and metabolomics revealed that O-GlcNAc transferase (OGT)-dependent O-GlcNAcylation and Gpx4-dependent ferroptosis may mediate the inflammatory protective effects of taurine on chondrocytes, which was further confirmed by gain and loss of function in vitro. Subsequently, further experiments indicated that the possible existence of a direct binding site for Gpx4 and OGT proteins, which provides evidence for the presence of O-GlcNAc modification of Gpx4 protein. Finnaly, we demonstrated that Gpx4-dependent ferroptosis and OGT-dependent O-GlcNAcylation may be potential mechanisms by which taurine protects against cartilage degeneration in vivo. CONCLUSION Antioxidant taurine inhibits chondrocyte ferroptosis through upregulation of OGT/Gpx4 signaling. Supplementation with taurine, a safe nonessential amino acid, may be a potential therapeutic strategy for OA.
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Affiliation(s)
- Xuchang Zhou
- Department of Rehabilitation Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China
| | - Yajing Yang
- Department of Acupuncture and Moxibustion, Hubei University of Chinese Medicine, Wuhan 430070, China
| | - Xu Qiu
- Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China
| | - Huili Deng
- Department of Rehabilitation Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China
| | - Hong Cao
- Faculty of Pharmaceutical Sciences, Shenzhen Institute of Advanced Technology, Shenzhen 518055, China
| | - Tao Liao
- Department of Rehabilitation Medicine, Chengdu Second People's Hospital, Chengdu 610000, China
| | - Xier Chen
- Department of Rehabilitation Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China
| | - Caihua Huang
- Research and Communication Center of Exercise and Health, Xiamen University of Technology, Xiamen 361024, China
| | - Donghai Lin
- Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
| | - Guoxin Ni
- Department of Rehabilitation Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China.
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Liang TL, Pan HD, Yan PY, Mi JN, Liu XC, Bao WQ, Lian LR, Zhang CF, Chen Y, Wang JR, Xie Y, Zhou H, Yao XJ, Graham P, Leung ELH, Liu L, Li RZ. Serum taurine affects lung cancer progression by regulating tumor immune escape mediated by the immune microenvironment. J Adv Res 2024:S2090-1232(24)00389-8. [PMID: 39243941 DOI: 10.1016/j.jare.2024.09.005] [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: 06/17/2024] [Revised: 08/19/2024] [Accepted: 09/02/2024] [Indexed: 09/09/2024] Open
Abstract
INTRODUCTION Taurine is a naturally occurring sulfonic acid involved in various physiological and pathological processes, such as the regulation of calcium signaling, immune function, inflammatory response, and cellular aging. It has the potential to predict tumor malignant transformation and formation. Our previous work discovered the elevated taurine in lung cancer patients. However, the precise impact and mechanism of elevated serum taurine levels on lung cancer progression and the suitability of taurine or taurine-containing drinks for lung cancer patients remain unclear. OBJECTIVES Our study aimed to systematically investigate the role of taurine in lung cancer, with the ultimate goal of contributing novel strategies for lung cancer treatment. METHODS Lung cancer C57 and nude mice models, RNA sequencing, and stable transfection were applied to explored the effects and mechanisms of taurine on lung cancer. Tissues of 129 non-small cell lung cancer (NSCLC) patients derived from 2014 to 2017 for immunohistochemistry were collected in Taihe Hospital. RESULTS Low doses of taurine, as well as taurine-infused beverages at equivalent doses, significantly enhanced lung tumor growth. Equally intriguing is that the promoting effect of taurine on lung cancer progression wanes as the dosage increases. The Nuclear factor erythroid 2-like 1 (Nfe2l1 or Nrf1)-reactive oxygen species (ROS)-PD-1 axis may be a potential mechanism for dual role of taurine in lung cancer progression. However, taurine's impacts on lung cancer progression and the anti-tumor function of Nfe2l1 were mainly determined by the immune competence. Taurine inhitited lung tumor growth probably by inhibiting NF-κB-mediated inflammatory responses in nude mice rather than by affecting Nfe2l1 function. As patients age increased, Nfe2l1 gene and protein gradually returned to the levels observed in healthy individuals, but lost its anti-lung cancer effects. CONCLUSIONS Taurine emerges as a potential biomarker for lung cancer progression, predicting poor prognosis and unsuitability for specific patients. Lung cancer patients, especially young patients, should be conscious of potential effects of taurine-containing drinks. Conversely, taurine or its drinks may be more suitable for older or immune-deficient patients.
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Affiliation(s)
- Tu-Liang Liang
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China
| | - Hu-Dan Pan
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China
| | - Pei-Yu Yan
- Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology, Macau (S.A.R.), China
| | - Jia-Ning Mi
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China
| | - Xiao-Cui Liu
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China
| | - Wei-Qian Bao
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China
| | - Li-Rong Lian
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China
| | - Cui-Fen Zhang
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China
| | - Ying Chen
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China
| | - Jing-Rong Wang
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China
| | - Ying Xie
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China
| | - Hua Zhou
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China
| | - Xiao-Jun Yao
- Faculty of Applied Sciences, Macao Polytechnic University, Macao, 999078, China
| | - Pawlec Graham
- Department of Immunology, University of Tübingen, Germany
| | - Elaine Lai-Han Leung
- Cancer Center, Faculty of Health Science, University of Macau, Macau (SAR), China; MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau (SAR), China.
| | - Liang Liu
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China.
| | - Run-Ze Li
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China.
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Su L, Luo H, Yan Y, Yang Z, Lu J, Xu D, Du L, Liu J, Yang G, Chi H. Exploiting gender-based biomarkers and drug targets: advancing personalized therapeutic strategies in hepatocellular carcinoma. Front Pharmacol 2024; 15:1433540. [PMID: 38966543 PMCID: PMC11222576 DOI: 10.3389/fphar.2024.1433540] [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: 05/16/2024] [Accepted: 06/04/2024] [Indexed: 07/06/2024] Open
Abstract
This review systematically examines gender differences in hepatocellular carcinoma (HCC), identifying the influence of sex hormones, genetic variance, and environmental factors on the disease's epidemiology and treatment outcomes. Recognizing the liver as a sexually dimorphic organ, we highlight how gender-specific risk factors, such as alcohol consumption and obesity, contribute differently to hepatocarcinogenesis in men and women. We explore molecular mechanisms, including the differential expression of androgen and estrogen receptors, which mediate diverse pathways in tumor biology such as cell proliferation, apoptosis, and DNA repair. Our analysis underscores the critical need for gender-specific research in liver cancer, from molecular studies to clinical trials, to improve diagnostic accuracy and therapeutic effectiveness. By incorporating a gender perspective into all facets of liver cancer research, we advocate for a more precise and personalized approach to cancer treatment that acknowledges gender as a significant factor in both the progression of HCC and its response to treatment. This review aims to foster a deeper understanding of the biological and molecular bases of gender differences in HCC and to promote the development of tailored interventions that enhance outcomes for all patients.
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Affiliation(s)
- Lanqian Su
- Clinical Medical College, Southwest Medical University, Luzhou, China
| | - Huanyu Luo
- Clinical Medical College, Southwest Medical University, Luzhou, China
| | - Yalan Yan
- Clinical Medical College, Southwest Medical University, Luzhou, China
| | - Zhongqiu Yang
- Department of General Surgery, Dazhou Central Hospital, Dazhou, China
| | - Jiaan Lu
- Clinical Medical College, Southwest Medical University, Luzhou, China
| | - Danqi Xu
- Clinical Medical College, Southwest Medical University, Luzhou, China
| | - Linjuan Du
- Department of Oncology, Dazhou Central Hospital, Dazhou, China
| | - Jie Liu
- Department of General Surgery, Dazhou Central Hospital, Dazhou, China
| | - Guanhu Yang
- Department of Specialty Medicine, Ohio University, Athens, OH, United States
| | - Hao Chi
- Clinical Medical College, Southwest Medical University, Luzhou, China
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Fan Z, Pan H, Qu N, Wang X, Cao L, Chen L, Liu M. LncRNA taurine upregulated gene 1 in liver disease. Clin Chim Acta 2024; 560:119752. [PMID: 38821337 DOI: 10.1016/j.cca.2024.119752] [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: 04/10/2024] [Revised: 05/24/2024] [Accepted: 05/27/2024] [Indexed: 06/02/2024]
Abstract
Long non-coding RNAs (lncRNAs) are RNA sequences exceeding 200 nucleotides in length that lack protein-coding capacity and participate in diverse biological processes in the human body, particularly exerting a pivotal role in disease surveillance, diagnosis, and progression. Taurine upregulated gene 1 (TUG1) is a versatile lncRNA, and recent studies have revealed that the aberrant expression or function of TUG1 is intricately linked to the pathogenesis of liver diseases. Consequently, we have summarized the current understanding of the mechanism of TUG1 in liver diseases such as liver fibrosis, fatty liver, cirrhosis, liver injury, hepatitis, and liver cancer. Moreover, mounting evidence suggests that interventions targeting TUG1 or its downstream pathways may hold therapeutic promise for liver diseases. This review elucidates the characteristics, mechanisms, and targets of TUG1 in liver diseases, offering a theoretical basis for the prevention, diagnosis, treatment, and prognostic biomarkers of liver diseases.
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Affiliation(s)
- Zihao Fan
- School of Pharmaceutical Sciences, Liaoning University, No. 66, Chongshan Mid Road, Shenyang 110036, China
| | - Hao Pan
- School of Pharmaceutical Sciences, Liaoning University, No. 66, Chongshan Mid Road, Shenyang 110036, China
| | - Na Qu
- School of Pharmaceutical Sciences, Liaoning University, No. 66, Chongshan Mid Road, Shenyang 110036, China
| | - Xin Wang
- School of Pharmaceutical Sciences, Liaoning University, No. 66, Chongshan Mid Road, Shenyang 110036, China
| | - Lianrui Cao
- School of Pharmaceutical Sciences, Liaoning University, No. 66, Chongshan Mid Road, Shenyang 110036, China
| | - Lijiang Chen
- School of Pharmaceutical Sciences, Liaoning University, No. 66, Chongshan Mid Road, Shenyang 110036, China.
| | - Mingxia Liu
- School of Pharmaceutical Sciences, Liaoning University, No. 66, Chongshan Mid Road, Shenyang 110036, China.
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Liang X, Zhang C, Shen L, Ding L, Guo H. Role of non‑coding RNAs in UV‑induced radiation effects (Review). Exp Ther Med 2024; 27:262. [PMID: 38756908 PMCID: PMC11097301 DOI: 10.3892/etm.2024.12550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 04/04/2024] [Indexed: 05/18/2024] Open
Abstract
Ultraviolet (UV) is divided into UVA (long-wave, 320-400 nm), UVB (middle-wave, 280-320 nm) and UVC (short-wave, 100-280 nm) based on wavelength. UV radiation (UVR) from sunlight (UVA + UVB) is a major cause of skin photodamage including skin inflammation, aging and pigmentation. Accidental exposure to UVC burns the skin and induces skin cancer. In addition to the skin, UV radiation can also impair visual function. Non-coding RNAs (ncRNAs) are a class of functional RNAs that do not have coding activity but can control cellular processes at the post-transcriptional level, including microRNA (miRNA), long non-coding RNA (lncRNA) and circulatory RNA (circRNA). Through a review of the literature, it was determined that UVR can affect the expression of various ncRNAs, and that this regulation may be wavelength specific. Functionally, ncRNAs participate in the regulation of photodamage through various pathways and play pathogenic or protective regulatory roles. In addition, ncRNAs that are upregulated or downregulated by UVR can serve as biomarkers for UV-induced diseases, aiding in diagnosis and prognosis assessment. Therapeutic strategies targeting ncRNAs, including the use of natural drugs and their extracts, have shown protective effects against UV-induced photodamage. In the present review, an extensive summarization of previous studies was performed and the role and mechanism of ncRNAs in UV-induced radiation effects was reviewed to aid in the diagnosis and treatment of UV-related diseases.
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Affiliation(s)
- Xiaofei Liang
- Department of Laboratory Medicine, The First Hospital of Qiqihar, Qiqihar, Heilongjiang 161000, P.R. China
| | - Chao Zhang
- Department of Laboratory Medicine, The First Hospital of Qiqihar, Qiqihar, Heilongjiang 161000, P.R. China
| | - Lijuan Shen
- Department of Laboratory Medicine, Qiqihar MingZhu Hospital, Qiqihar, Heilongjiang 161000, P.R. China
| | - Ling Ding
- Department of Laboratory Medicine, The First Hospital of Qiqihar, Qiqihar, Heilongjiang 161000, P.R. China
| | - Haipeng Guo
- Department of Laboratory Medicine, The First Hospital of Qiqihar, Qiqihar, Heilongjiang 161000, P.R. China
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Kattner AA. And those who were seen dancing: Human interactions with fungi and vice versa. Biomed J 2024; 47:100755. [PMID: 38901797 PMCID: PMC11245968 DOI: 10.1016/j.bj.2024.100755] [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: 06/15/2024] [Accepted: 06/17/2024] [Indexed: 06/22/2024] Open
Abstract
This issue of the Biomedical Journal features a special section exploring mycobiota. Three articles examine the role of fungi in common metabolic disorders in, Clostridium difficile infection, and in immunocompromised patients. Additionally, the potential and challenges of the metaverse in healthcare are reviewed, alongside a holistic approach to improve patient outcomes in pancreatic cancer. In this issue also possible mechanism contributing to long COVID are discussed, as well as biomarkers that effectively predict sepsis outcomes, and key targets in osteosarcoma progression. Moreover, factors leading to peri-intubation cardiac arrest are analyzed, healthcare strategies from various regions are employed to predict cardiovascular events in Asian populations, two approaches to cavernous sinus dural arteriovenous fistula are compared, and a combination therapy against soft tissue sarcoma is presented.
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Peng Y, Zhang M, Hu J. Non-coding RNAs involved in fibroblast-like synoviocyte functioning in arthritis rheumatoid: From pathogenesis to therapy. Cytokine 2024; 173:156418. [PMID: 37952312 DOI: 10.1016/j.cyto.2023.156418] [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: 10/15/2023] [Revised: 10/27/2023] [Accepted: 10/31/2023] [Indexed: 11/14/2023]
Abstract
Rheumatoid arthritis (RA) is a polygenic autoimmune disorder with an uncertain etiology, primarily impacting the joints. Moreover, the disease may manifest beyond articular involvement, leading to extra-articular manifestations. Fibroblast-like synoviocytes (FLS) are cells of mesenchymal origin that possess crucial physiological significance within the synovium, contributing to the synthesis of specific constituents found in the synovial fluid and articular cartilage. Consequently, there has been a growing focus on FLS as a potential therapeutic target in the context of RA. Recent investigations have revealed that non-coding RNAs (ncRNAs) serve as pivotal regulators of FLS function, with their dysregulated expression patterns being detected within FLS populations. NcRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), assume essential functions as regulators of gene expression at both the post-transcriptional and transcriptional levels, and also serve as guiding molecules for chromatin-modifying complexes. Majority of these ncRNAs contribute to various FLS activities including metastasis, proliferation, and cytokine production. In the current work, we comprehensively review the existing literature on ncRNAs, which play pivotal roles in FLS activity and the pathogenesis of RA. Furthermore, this study provides a comprehensive summary and description of the lncRNA/circRNA-miRNA-mRNA regulatory axes in FLS activity, along with potential implications for the RA development. As well, in the final section, we illustrated that therapeutic agents including herbal medicine, and exosomes by modulating ncRNAs regulate FLS activity.
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Affiliation(s)
- Yuwei Peng
- Rheumatology and Immunology, PingXiangPeople's Hospital, No. 8, Wugongshangzhong Avenue, Anyuan District, PiangXiang City, Jiangxi Province, 337000, China
| | - Meng Zhang
- Rheumatology and Immunology, PingXiangPeople's Hospital, No. 8, Wugongshangzhong Avenue, Anyuan District, PiangXiang City, Jiangxi Province, 337000, China
| | - Jiangkang Hu
- Rheumatology and Immunology, PingXiangPeople's Hospital, No. 8, Wugongshangzhong Avenue, Anyuan District, PiangXiang City, Jiangxi Province, 337000, China.
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11
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Marques IS, Tavares V, Savva-Bordalo J, Rei M, Liz-Pimenta J, de Melo IG, Assis J, Pereira D, Medeiros R. Long Non-Coding RNAs: Bridging Cancer-Associated Thrombosis and Clinical Outcome of Ovarian Cancer Patients. Int J Mol Sci 2023; 25:140. [PMID: 38203310 PMCID: PMC10778953 DOI: 10.3390/ijms25010140] [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: 11/01/2023] [Revised: 12/18/2023] [Accepted: 12/19/2023] [Indexed: 01/12/2024] Open
Abstract
Ovarian cancer (OC) and venous thromboembolism (VTE) have a close relationship, in which tumour cells surpass the haemostatic system to drive cancer progression. Long non-coding RNAs (lncRNAs) have been implicated in VTE pathogenesis, yet their roles in cancer-associated thrombosis (CAT) and their prognostic value are unexplored. Understanding how these lncRNAs influence venous thrombogenesis and ovarian tumorigenesis may lead to the identification of valuable biomarkers for VTE and OC management. Thus, this study evaluated the impact of five lncRNAs, namely MALAT1, TUG1, NEAT1, XIST and MEG8, on a cohort of 40 OC patients. Patients who developed VTE after OC diagnosis had worse overall survival compared to their counterparts (log-rank test, p = 0.028). Elevated pre-chemotherapy MEG8 levels in peripheral blood cells (PBCs) predicted VTE after OC diagnosis (Mann-Whitney U test, p = 0.037; Χ2 test, p = 0.033). In opposition, its low levels were linked to a higher risk of OC progression (adjusted hazard ratio (aHR) = 3.00; p = 0.039). Furthermore, low pre-chemotherapy NEAT1 levels in PBCs were associated with a higher risk of death (aHR = 6.25; p = 0.008). As for the remaining lncRNAs, no significant association with VTE incidence, OC progression or related mortality was observed. Future investigation with external validation in larger cohorts is needed to dissect the implications of the evaluated lncRNAs in OC patients.
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Affiliation(s)
- Inês Soares Marques
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Department, Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto.CCC), 4200-072 Porto, Portugal; (I.S.M.); (V.T.); (I.G.d.M.)
- Faculty of Sciences of the University of Porto (FCUP), 4169-007 Porto, Portugal
| | - Valéria Tavares
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Department, Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto.CCC), 4200-072 Porto, Portugal; (I.S.M.); (V.T.); (I.G.d.M.)
- Faculty of Medicine of the University of Porto (FMUP), 4200-072 Porto, Portugal;
- Abel Salazar Institute for the Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal
| | - Joana Savva-Bordalo
- Department of Medical Oncology, Portuguese Institute of Oncology of Porto (IPO Porto), 4200-072 Porto, Portugal; (J.S.-B.); (D.P.)
| | - Mariana Rei
- Department of Gynaecology, Portuguese Institute of Oncology of Porto (IPO Porto), 4200-072 Porto, Portugal;
| | - Joana Liz-Pimenta
- Faculty of Medicine of the University of Porto (FMUP), 4200-072 Porto, Portugal;
- Department of Medical Oncology, Centro Hospitalar de Trás-os-Montes e Alto Douro (CHTMAD), 5000-508 Vila Real, Portugal
| | - Inês Guerra de Melo
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Department, Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto.CCC), 4200-072 Porto, Portugal; (I.S.M.); (V.T.); (I.G.d.M.)
- Faculty of Medicine of the University of Porto (FMUP), 4200-072 Porto, Portugal;
| | - Joana Assis
- Clinical Research Unit, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal;
| | - Deolinda Pereira
- Department of Medical Oncology, Portuguese Institute of Oncology of Porto (IPO Porto), 4200-072 Porto, Portugal; (J.S.-B.); (D.P.)
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Department, Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto.CCC), 4200-072 Porto, Portugal; (I.S.M.); (V.T.); (I.G.d.M.)
- Faculty of Medicine of the University of Porto (FMUP), 4200-072 Porto, Portugal;
- Abel Salazar Institute for the Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal
- Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal
- Research Department, Portuguese League Against Cancer (NRNorte), 4200-172 Porto, Portugal
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12
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Yousf S, Malla JA, Sardesai DM, Sharma S, Talukdar P, Chugh J. Mapping metabolic perturbations induced by glutathione activatable synthetic ion channels in human breast cancer cells. J Pharm Biomed Anal 2023; 235:115605. [PMID: 37531734 DOI: 10.1016/j.jpba.2023.115605] [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: 06/05/2023] [Revised: 07/24/2023] [Accepted: 07/25/2023] [Indexed: 08/04/2023]
Abstract
Ion channels and transporters play key roles in various biological processes, including cell proliferation and programmed cell death. Recently, we reported that 2,4-dinitrobenzene-sulfonyl-protected N1,N3-dihexy-2-hydroxyisophthalamide (1) forms ion channels upon activation by glutathione (GSH) and results in the induction of apoptosis by depleting the intracellular GSH reservoir in cancer cells. However, the detailed molecular events leading to the induction of apoptosis by these synthetic transport systems in cancer cells still need to be uncovered. Along these lines, we investigated the alterations in cellular metabolites and the associated metabolic pathways by performing untargeted global metabolic profiling of breast cancer cells - MCF-7 - using 1H NMR-based metabolomics. The evaluation of spectral profiles from MCF-7 cells exposed to 1 and their comparison with those corresponding to untreated (control) cells identified 14 significantly perturbed signature metabolites. These metabolites belonged mostly to antioxidant defence, energy metabolism, amino acid biosynthesis, and lipid metabolism pathways and included GSH, o-phosphocholine, malate, and aspartate, to name a few. These results would help us gain deeper insights into the molecular mechanism underlying 1-mediated cytotoxicity of MCF-7 cells and eventually help identify potential novel therapeutic targets for more effective cancer management.
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Affiliation(s)
- Saleem Yousf
- Department of Chemistry, Indian Institute of Science Education and Research (IISER), Dr. Homi Bhabha Road, Pashan, Pune 411008, India.
| | - Javid A Malla
- Department of Chemistry, Indian Institute of Science Education and Research (IISER), Dr. Homi Bhabha Road, Pashan, Pune 411008, India
| | - Devika M Sardesai
- Department of Biotechnology, Savitribai Phule Pune University (SPPU), Ganeshkhind, Pune 411007, India
| | - Shilpy Sharma
- Department of Biotechnology, Savitribai Phule Pune University (SPPU), Ganeshkhind, Pune 411007, India
| | - Pinaki Talukdar
- Department of Chemistry, Indian Institute of Science Education and Research (IISER), Dr. Homi Bhabha Road, Pashan, Pune 411008, India
| | - Jeetender Chugh
- Department of Chemistry, Indian Institute of Science Education and Research (IISER), Dr. Homi Bhabha Road, Pashan, Pune 411008, India.
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13
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Chen X, Zhu X, Yan W, Wang L, Xue D, Zhu S, Pan J, Li Y, Zhao Q, Han D. Serum lncRNA THRIL predicts benign and malignant pulmonary nodules and promotes the progression of pulmonary malignancies. BMC Cancer 2023; 23:755. [PMID: 37582734 PMCID: PMC10426220 DOI: 10.1186/s12885-023-11264-9] [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: 03/21/2023] [Accepted: 08/06/2023] [Indexed: 08/17/2023] Open
Abstract
BACKGROUND This project aimed to research the significance of THRIL in the diagnosis of benign and malignant solitary pulmonary nodules (SPNs) and to investigate the role of THRIL/miR-99a in malignant SPNs. METHODS The study groups consisted of 169 patients with SPN and 74 healthy subjects. The differences in THRIL levels were compared between the two groups and the healthy group. The receiver operating characteristic curve (ROC) was utilized to analyze the THRIL's significance in detecting benign and malignant SPN. Pearson correlation and binary regression coefficients represented the association between THRIL and SPN. CCK-8 assay, Transwell assay, and flow cytometry were utilized to detect the regulatory effect of THRIL silencing. The interaction between THRIL, miR-99a, and IGF1R was confirmed by the double luciferase reporter gene. RESULTS There were differences in THRIL expression in the healthy group, benign SPN group, and malignant SPN group. High accuracy of THRIL in the diagnosis of benign SPN and malignant SPN was observed. THRIL was associated with the development of SPN. The expression of THRIL was upregulated and miR-99a was downregulated in lung cancer cells. The double luciferase report experiment confirmed the connections between THRIL/miR-99a/IGF1R. Silencing THRIL could suppress cell proliferation, migration, and invasion and promote cell apoptosis by binding miR-99a. CONCLUSION The detection of THRIL in serum is useful for the assessment of malignant SPN. THRIL can regulate the expression of IGF1R through miR-99a, thereby promoting the growth of lung cancer cells and inhibiting apoptosis.
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Affiliation(s)
- Xinyu Chen
- Department of Cardiothoracic Surgery, Xuzhou No.1 People's Hospital, Xuzhou Municipal Hospital Affiliated with Xuzhou Medical College, 269 Daxue Road, Xuzhou, 221000, China
| | - Xianji Zhu
- Department of Respiratory Medicine, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China
| | - Wenjun Yan
- Department of Cardiothoracic Surgery, Xuzhou No.1 People's Hospital, Xuzhou Municipal Hospital Affiliated with Xuzhou Medical College, 269 Daxue Road, Xuzhou, 221000, China
| | - Luan Wang
- Department of Cardiothoracic Surgery, Xuzhou No.1 People's Hospital, Xuzhou Municipal Hospital Affiliated with Xuzhou Medical College, 269 Daxue Road, Xuzhou, 221000, China
| | - Dongming Xue
- Department of Cardiothoracic Surgery, Xuzhou No.1 People's Hospital, Xuzhou Municipal Hospital Affiliated with Xuzhou Medical College, 269 Daxue Road, Xuzhou, 221000, China
| | - Shouying Zhu
- Department of Cardiothoracic Surgery, Xuzhou No.1 People's Hospital, Xuzhou Municipal Hospital Affiliated with Xuzhou Medical College, 269 Daxue Road, Xuzhou, 221000, China
| | - Jiajun Pan
- Department of Cardiothoracic Surgery, Xuzhou No.1 People's Hospital, Xuzhou Municipal Hospital Affiliated with Xuzhou Medical College, 269 Daxue Road, Xuzhou, 221000, China
| | - Yufeng Li
- Department of Cardiothoracic Surgery, Xuzhou No.1 People's Hospital, Xuzhou Municipal Hospital Affiliated with Xuzhou Medical College, 269 Daxue Road, Xuzhou, 221000, China
| | - Qixiang Zhao
- Department of Cardiothoracic Surgery, Xuzhou No.1 People's Hospital, Xuzhou Municipal Hospital Affiliated with Xuzhou Medical College, 269 Daxue Road, Xuzhou, 221000, China
| | - Dong Han
- Department of Cardiothoracic Surgery, Xuzhou No.1 People's Hospital, Xuzhou Municipal Hospital Affiliated with Xuzhou Medical College, 269 Daxue Road, Xuzhou, 221000, China.
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Xu S, Lin J, Chen R, Xie J, Yuan E, Cen F, Kong F. LINC00174 Promotes Colon Cancer Progression by Regulating Inflammation and Glycolysis by Targeting the MicroRNA-2467-3p/Enolase 3 Axis. Mediators Inflamm 2023; 2023:8052579. [PMID: 37448887 PMCID: PMC10338131 DOI: 10.1155/2023/8052579] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 05/03/2023] [Accepted: 05/23/2023] [Indexed: 07/15/2023] Open
Abstract
OBJECTIVE To elucidate the mechanism by which LINC00174 promotes colon cancer progression by targeting the microRNA-2467-3p (miR-2467-3p)/enolase 3 (ENO3) axis to regulate inflammation and glycolysis. METHODS The expression of LINC00174 and ENO3 in colon cancer tissues, its relationship with survival rate, and correlation were analyzed using bioinformatic analysis. The effects of LINC00174 overexpression and silencing on the biological behavior of and inflammation in colon cancer cells were analyzed via transfection experiments. The target relationships between miR-2467-3p or LINC00174 and ENO3 were verified using sequence prediction and the dual-luciferase reporter assay, respectively. Furthermore, LINC00174- and/or miR-2467-3p-overexpressing cells were prepared to determine the effects on ENO3 protein levels and glycolysis. Finally, the effects of LINC00174 and/or miR-2467-3p overexpression on colon cancer, ENO3 protein levels, and inflammation were analyzed using a tumor-bearing mice model. RESULTS LINC00174 and ENO3 were overexpressed and associated with a lower survival rate. LINC00174 was positively correlated with ENO3 in colon cancer tissues. Furthermore, the overexpression of LINC00174 in colon cancer cell lines promoted the proliferation, migration, and invasion of colon cancer cells and inflammation but inhibited apoptosis. The overexpression of miR-2467-3p inhibited ENO3 protein levels, which was attenuated via LINC00174 overexpression. Furthermore, it inhibited the biological behavior of and inflammation and glycolysis in colon cancer cells and blocked their LINC00174-induced promotion. Moreover, using animal experiments, the regulatory effects of LINC00174 on tumor growth, ENO3 protein levels, and inflammation via miR-2467-3p were confirmed. CONCLUSION LINC00174 promotes the glycolysis, inflammation, proliferation, migration, and invasion of colon cancer cells and inhibits apoptosis. The cancer-promoting mechanism of LINC00174 is related to targeting miR-2467-3p to promote ENO3 protein levels.
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Affiliation(s)
- Sheng Xu
- Department of General Surgery, People's Hospital of Guangxi Zhuang Autonomous Region, 530021 Nanning, China
| | - Jiawei Lin
- Department of General Surgery, People's Hospital of Guangxi Zhuang Autonomous Region, 530021 Nanning, China
| | - Rong Chen
- Department of General Surgery, People's Hospital of Guangxi Zhuang Autonomous Region, 530021 Nanning, China
| | - Junjie Xie
- Oncology Department, General Hospital of Central Theater Command, Wuluo 627, Wuhan, 430070 Hubei Province, China
| | - Enquan Yuan
- Department of General Surgery, People's Hospital of Guangxi Zhuang Autonomous Region, 530021 Nanning, China
| | - Fajie Cen
- Department of General Surgery, People's Hospital of Guangxi Zhuang Autonomous Region, 530021 Nanning, China
| | - Fanbiao Kong
- Department of General Surgery, People's Hospital of Guangxi Zhuang Autonomous Region, 530021 Nanning, China
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15
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Jun N, Yi‐Ting C, Yu‐Ting G, Cheng‐Fa Z, Li‐Juan L, Rong S, Xiao‐yan Y, Wen X, Xu Y. Antioxidant, anti-inflammatory, and anticancer function of Engleromyces goetzei Henn aqueous extract on human intestinal Caco-2 cells treated with t-BHP. Food Sci Nutr 2023; 11:3450-3463. [PMID: 37324905 PMCID: PMC10261740 DOI: 10.1002/fsn3.3335] [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: 10/28/2022] [Revised: 02/20/2023] [Accepted: 02/26/2023] [Indexed: 04/08/2023] Open
Abstract
High body mass index (high BMI, obesity) is a serious public health problem, and "obesity-induced oxidative stress, inflammation, and cancer" have become modern epidemic diseases. We carried out this study to explore a functional beverage that may protect against obesity-induced diseases. The Engleromyces goetzei Henn herbal tea is such a candidate. For this study, we carried out LC-MS analysis of E. goetzei Henn aqueous extract (EgH-AE); then used the Caco-2 cell line for the model cells and treated the cells with t-BHP to form an oxidative stress system. An MTT assay was used for testing the biocompatibility and cytoprotective effects; reactive oxygen species and malondialdehyde determination was used for evaluating the antioxidative stress effect; TNF-α and IL-1β were used for observing the anti-inflammatory effect, and 8-OHdG for monitoring anticancer activity. The results of this study demonstrate that the EgH-AE has very good biocompatibility with the Caco-2 cell line and has good cytoprotective, antioxidant, anti-inflammatory, and anticancer properties. It is clear that EgH-AE, a kind of ancient herbal tea, may be used to develop a functional beverage that can be given to people with a high BMI to protect against obesity-induced diseases.
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Affiliation(s)
- Ni Jun
- Institute of Natural Antioxidants and Antioxidant InflammationDali UniversityDali671003China
- Institute of Eastern‐Himalaya Biodiversity ResearchDali UniversityDaliYunnanChina
| | - Cheng Yi‐Ting
- Institute of Natural Antioxidants and Antioxidant InflammationDali UniversityDali671003China
- Institute of Eastern‐Himalaya Biodiversity ResearchDali UniversityDaliYunnanChina
| | - Gao Yu‐Ting
- Institute of Natural Antioxidants and Antioxidant InflammationDali UniversityDali671003China
- Institute of Eastern‐Himalaya Biodiversity ResearchDali UniversityDaliYunnanChina
| | - Zhao Cheng‐Fa
- Institute of Natural Antioxidants and Antioxidant InflammationDali UniversityDali671003China
- Institute of Eastern‐Himalaya Biodiversity ResearchDali UniversityDaliYunnanChina
| | - Li Li‐Juan
- Institute of Natural Antioxidants and Antioxidant InflammationDali UniversityDali671003China
| | - She Rong
- Institute of Natural Antioxidants and Antioxidant InflammationDali UniversityDali671003China
- Institute of Eastern‐Himalaya Biodiversity ResearchDali UniversityDaliYunnanChina
| | - Yang Xiao‐yan
- Institute of Natural Antioxidants and Antioxidant InflammationDali UniversityDali671003China
- Institute of Eastern‐Himalaya Biodiversity ResearchDali UniversityDaliYunnanChina
| | - Xiao Wen
- Institute of Natural Antioxidants and Antioxidant InflammationDali UniversityDali671003China
- Institute of Eastern‐Himalaya Biodiversity ResearchDali UniversityDaliYunnanChina
- Center for Cultural Ecology in Northwest YunnanDaliYunnan671003China
- Yunling Back‐and‐White Snub‐Nosed Monkey Observation and Research Station of Yunnan ProvinceDaliYunnan671003China
| | - Yang Xu
- Institute of Natural Antioxidants and Antioxidant InflammationDali UniversityDali671003China
- Laboratory of Environmental BiomedicineCentral China Normal University430079WuhanChina
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Yang BY, Zhao FZ, Li XH, Zhao MS, Lv JC, Shi MJ, Li J, Zhou ZY, Wang JJ, Song J. Alteration of pro-carcinogenic gut microbiota is associated with clear cell renal cell carcinoma tumorigenesis. Front Microbiol 2023; 14:1133782. [PMID: 37089532 PMCID: PMC10113506 DOI: 10.3389/fmicb.2023.1133782] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/21/2023] [Indexed: 04/08/2023] Open
Abstract
ObjectiveIncreasing evidence suggests that gut microbiota is involved in the occurrence and progression of urinary system diseases such as clear cell renal cell carcinoma (ccRCC). However, the mechanism of how alteration of gut metagenome promotes ccRCC remains unclear. Here we aim to elucidate the association of specific gut bacteria and their metabolites with ccRCC.MethodsIn a pilot case-control study among 30 ccRCC patients (RCC group) and 30 healthy controls (Control group), 16S ribosomal RNA (rRNA) gene sequencing were analyzed from fecal samples collected prior to surgery or hospitalization. Alpha diversity and beta diversity analysis of the gut microbiota were performed, and differential taxa were identified by multivariate statistics. Meanwhile, serum metabolism was measured by UHPLC-MS, and differential genes were identified based on the TCGA database.ResultsAlpha diversity found there were no significant microbial diversity differences of gut microbiota between the RCC group and the Control group. However, beta diversity analysis showed that the overall structures of the two groups were significantly separated (p = 0.008). Random Forests revealed the relative abundances of 20 species differed significantly between the RCC group and the Control group, among which nine species were enriched in the RCC group such as Desulfovibrionaceae, and 11 species were less abundant such as four kinds of Lactobacillus. Concomitantly, serum level of taurine, which was considered to be consumed by Desulfovibrionaceae and released by Lactobacillus, has decreased in the RCC group. In addition, macrophage-related genes such as Gabbr1 was upregulated in ccRCC patients.ConclusionReduction of protective bacteria, proliferation of sulfide-degrading bacteria Desulfovibrionaceae, reduction of taurine, and enrichment of macrophage related genes might be the risk predictors of ccRCC.
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Affiliation(s)
- Bo-Yu Yang
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Fang-Zhou Zhao
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xuan-Hao Li
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Mei-Shan Zhao
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jing-Cheng Lv
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Ming-Jun Shi
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jun Li
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Zhi-Yuan Zhou
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Shanghai Pudong New Area Gongli Hospital, Shanghai, China
- *Correspondence: Zhi-Yuan Zhou,
| | - Jing-Jing Wang
- Shanghai Key Laboratory of Pancreatic Diseases, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Jing-Jing Wang,
| | - Jian Song
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Jian Song,
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O’Connell F, Mylod E, Donlon NE, Heeran AB, Butler C, Bhardwaj A, Ramjit S, Durand M, Lambe G, Tansey P, Welartne I, Sheahan KP, Yin X, Donohoe CL, Ravi N, Dunne MR, Brennan L, Reynolds JV, Roche HM, O’Sullivan J. Energy Metabolism, Metabolite, and Inflammatory Profiles in Human Ex Vivo Adipose Tissue Are Influenced by Obesity Status, Metabolic Dysfunction, and Treatment Regimes in Patients with Oesophageal Adenocarcinoma. Cancers (Basel) 2023; 15:cancers15061681. [PMID: 36980567 PMCID: PMC10046380 DOI: 10.3390/cancers15061681] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/01/2023] [Accepted: 03/02/2023] [Indexed: 03/12/2023] Open
Abstract
Oesophageal adenocarcinoma (OAC) is a poor prognosis cancer with limited response rates to current treatment modalities and has a strong link to obesity. To better elucidate the role of visceral adiposity in this disease state, a full metabolic profile combined with analysis of secreted pro-inflammatory cytokines, metabolites, and lipid profiles were assessed in human ex vivo adipose tissue explants from obese and non-obese OAC patients. These data were then related to extensive clinical data including obesity status, metabolic dysfunction, previous treatment exposure, and tumour regression grades. Real-time energy metabolism profiles were assessed using the seahorse technology. Adipose explant conditioned media was screened using multiplex ELISA to assess secreted levels of 54 pro-inflammatory mediators. Targeted secreted metabolite and lipid profiles were analysed using Ultra-High-Performance Liquid Chromatography coupled with Mass Spectrometry. Adipose tissue explants and matched clinical data were collected from OAC patients (n = 32). Compared to visceral fat from non-obese patients (n = 16), visceral fat explants from obese OAC patients (n = 16) had significantly elevated oxidative phosphorylation metabolism profiles and an increase in Eotaxin-3, IL-17A, IL-17D, IL-3, MCP-1, and MDC and altered secretions of glutamine associated metabolites. Adipose explants from patients with metabolic dysfunction correlated with increased oxidative phosphorylation metabolism, and increases in IL-5, IL-7, SAA, VEGF-C, triacylglycerides, and metabolites compared with metabolically healthy patients. Adipose explants generated from patients who had previously received neo-adjuvant chemotherapy (n = 14) showed elevated secretions of pro-inflammatory mediators, IL-12p40, IL-1α, IL-22, and TNF-β and a decreased expression of triacylglycerides. Furthermore, decreased secreted levels of triacylglycerides were also observed in the adipose secretome of patients who received the chemotherapy-only regimen FLOT compared with patients who received no neo-adjuvant treatment or chemo-radiotherapy regimen CROSS. For those patients who showed the poorest response to currently available treatments, their adipose tissue was associated with higher glycolytic metabolism compared to patients who had good treatment responses. This study demonstrates that the adipose secretome in OAC patients is enriched with mediators that could prime the tumour microenvironment to aid tumour progression and attenuate responses to conventional cancer treatments, an effect which appears to be augmented by obesity and metabolic dysfunction and exposure to different treatment regimes.
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Affiliation(s)
- Fiona O’Connell
- Department of Surgery, Trinity St. James’s Cancer Institute and Trinity Translational Medicine Institute, St. James’s Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland
| | - Eimear Mylod
- Department of Surgery, Trinity St. James’s Cancer Institute and Trinity Translational Medicine Institute, St. James’s Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland
- Cancer Immunology and Immunotherapy Group, Department of Surgery, Trinity College Dublin, St. James’s Hospital, D08 W9RT Dublin, Ireland
| | - Noel E. Donlon
- Department of Surgery, Trinity St. James’s Cancer Institute and Trinity Translational Medicine Institute, St. James’s Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland
- Cancer Immunology and Immunotherapy Group, Department of Surgery, Trinity College Dublin, St. James’s Hospital, D08 W9RT Dublin, Ireland
| | - Aisling B. Heeran
- Department of Surgery, Trinity St. James’s Cancer Institute and Trinity Translational Medicine Institute, St. James’s Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland
| | - Christine Butler
- Department of Surgery, Trinity St. James’s Cancer Institute and Trinity Translational Medicine Institute, St. James’s Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland
| | - Anshul Bhardwaj
- Department of Surgery, Trinity St. James’s Cancer Institute and Trinity Translational Medicine Institute, St. James’s Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland
| | - Sinead Ramjit
- Department of Surgery, Trinity St. James’s Cancer Institute and Trinity Translational Medicine Institute, St. James’s Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland
| | - Michael Durand
- Department of Radiology, St. James’s Hospital, D08 NHY1 Dublin, Ireland
| | - Gerard Lambe
- Department of Radiology, St. James’s Hospital, D08 NHY1 Dublin, Ireland
| | - Paul Tansey
- Department of Radiology, St. James’s Hospital, D08 NHY1 Dublin, Ireland
| | - Ivan Welartne
- Department of Radiology, St. James’s Hospital, D08 NHY1 Dublin, Ireland
| | - Kevin P. Sheahan
- Department of Radiology, Beaumont Hospital, D02 YN77 Dublin, Ireland
| | - Xiaofei Yin
- UCD School of Agriculture and Food Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland
| | - Claire L. Donohoe
- Department of Surgery, Trinity St. James’s Cancer Institute and Trinity Translational Medicine Institute, St. James’s Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland
| | - Narayanasamy Ravi
- Department of Surgery, Trinity St. James’s Cancer Institute and Trinity Translational Medicine Institute, St. James’s Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland
| | - Margaret R. Dunne
- Department of Surgery, Trinity St. James’s Cancer Institute and Trinity Translational Medicine Institute, St. James’s Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland
- School of Chemical & Biopharmaceutical Sciences, Technological University Dublin, Tallaght, D07 EWV4 Dublin, Ireland
| | - Lorraine Brennan
- UCD School of Agriculture and Food Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland
| | - John V. Reynolds
- Department of Surgery, Trinity St. James’s Cancer Institute and Trinity Translational Medicine Institute, St. James’s Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland
| | - Helen M. Roche
- Nutrigenomics Research Group, UCD Conway Institute, School of Public Health, Physiotherapy and Sports Science, University College Dublin, D04 C1P1 Dublin, Ireland
- Institute for Global Food Security, School of Biological Sciences, Queens University Belfast, Belfast BT9 5DL, UK
| | - Jacintha O’Sullivan
- Department of Surgery, Trinity St. James’s Cancer Institute and Trinity Translational Medicine Institute, St. James’s Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland
- Correspondence:
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18
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Stary D, Bajda M. Taurine and Creatine Transporters as Potential Drug Targets in Cancer Therapy. Int J Mol Sci 2023; 24:ijms24043788. [PMID: 36835201 PMCID: PMC9964810 DOI: 10.3390/ijms24043788] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/07/2023] [Accepted: 02/10/2023] [Indexed: 02/16/2023] Open
Abstract
Cancer cells are characterized by uncontrolled growth, proliferation, and impaired apoptosis. Tumour progression could be related to poor prognosis and due to this fact, researchers have been working on novel therapeutic strategies and antineoplastic agents. It is known that altered expression and function of solute carrier proteins from the SLC6 family could be associated with severe diseases, including cancers. These proteins were noticed to play important physiological roles through transferring nutrient amino acids, osmolytes, neurotransmitters, and ions, and many of them are necessary for survival of the cells. Herein, we present the potential role of taurine (SLC6A6) and creatine (SLC6A8) transporters in cancer development as well as therapeutic potential of their inhibitors. Experimental data indicate that overexpression of analyzed proteins could be connected with colon or breast cancers, which are the most common types of cancers. The pool of known inhibitors of these transporters is limited; however, one ligand of SLC6A8 protein is currently tested in the first phase of clinical trials. Therefore, we also highlight structural aspects useful for ligand development. In this review, we discuss SLC6A6 and SLC6A8 transporters as potential biological targets for anticancer agents.
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Affiliation(s)
- Dorota Stary
- Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 St., 30-688 Cracow, Poland
- Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, św. Łazarza 16 St., 31-530 Cracow, Poland
| | - Marek Bajda
- Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 St., 30-688 Cracow, Poland
- Correspondence:
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19
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Zhu S, Han X, Yang R, Tian Y, Zhang Q, Wu Y, Dong S, Zhang B. Metabolomics study of ribavirin in the treatment of orthotopic lung cancer based on UPLC-Q-TOF/MS. Chem Biol Interact 2023; 370:110305. [PMID: 36529159 DOI: 10.1016/j.cbi.2022.110305] [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: 06/24/2022] [Revised: 12/06/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022]
Abstract
Ribavirin is a common antiviral drug, especially for patients with hepatitis C. Our recent studies demonstrated that ribavirin showed anti-tumor activity in colorectal cancer and hepatocellular carcinoma, but its effects on lung cancer remains unclear. This study aimed to evaluate the anti-tumor activity of ribavirin against lung cancer and elucidate the underlying mechanism. We established orthotopic mouse model of lung cancer (LLC and GLC-82) and employed an ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics approach. We found that ribavirin significantly inhibited the proliferation and colony formation of lung cancer cells. Tumor sizes of orthotopic lung cancer in ribavirin-treated groups were also significantly lower than those in control groups. Metabolomics analysis revealed that ribavirin mainly affected 5 metabolic pathways in orthotopic lung tumor models, taurine and hypotaurine metabolism, nicotinate and nicotinamide metabolism, linoleic acid metabolism, arginine biosynthesis and arachidonic acid metabolism. Furthermore, we identified 5 upregulated metabolites including β-nicotinamide adenine dinucleotide (NAD+), nicotinamide (NAM), taurine, ornithine and citrulline, and 7 downregulated metabolites including 1-methylnicotinamide (MNAM), S-adenosyl-l-homocysteine (SAH), N1-Methyl-2-pyridone-5-carboxamide (2PY), homocysteine (Hcy), linoleic acid, arachidonic acid (AA) and argininosuccinic acid in ribavirin-treated groups. These results provide new insight into the anti-tumor mechanism of ribavirin for lung cancer.
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Affiliation(s)
- Shihao Zhu
- Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China
| | - Xiang Han
- Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China
| | - Ruiying Yang
- Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China
| | - Yizhen Tian
- Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China
| | - Qingqing Zhang
- Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China
| | - Yongjie Wu
- Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China
| | - Shuhong Dong
- Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
| | - Baolai Zhang
- Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
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20
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Feng J, Gong Z, Sun Z, Li J, Xu N, Thorne RF, Zhang XD, Liu X, Liu G. Microbiome and metabolic features of tissues and feces reveal diagnostic biomarkers for colorectal cancer. Front Microbiol 2023; 14:1034325. [PMID: 36712187 PMCID: PMC9880203 DOI: 10.3389/fmicb.2023.1034325] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 01/02/2023] [Indexed: 01/15/2023] Open
Abstract
Microbiome and their metabolites are increasingly being recognized for their role in colorectal cancer (CRC) carcinogenesis. Towards revealing new CRC biomarkers, we compared 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) metabolite analyses in 10 CRC (TCRC) and normal paired tissues (THC) along with 10 matched fecal samples (FCRC) and 10 healthy controls (FHC). The highest microbial phyla abundance from THC and TCRC were Firmicutes, while the dominant phyla from FHC and FCRC were Bacteroidetes, with 72 different microbial genera identified among four groups. No changes in Chao1 indices were detected between tissues or between fecal samples whereas non-metric multidimensional scaling (NMDS) analysis showed distinctive clusters among fecal samples but not tissues. LEfSe analyses indicated Caulobacterales and Brevundimonas were higher in THC than in TCRC, while Burkholderialese, Sutterellaceaed, Tannerellaceaea, and Bacteroidaceae were higher in FHC than in FCRC. Microbial association networks indicated some genera had substantially different correlations. Tissue and fecal analyses indicated lipids and lipid-like molecules were the most abundant metabolites detected in fecal samples. Moreover, partial least squares discriminant analysis (PLS-DA) based on metabolic profiles showed distinct clusters for CRC and normal samples with a total of 102 differential metabolites between THC and TCRC groups and 700 metabolites different between FHC and FCRC groups. However, only Myristic acid was detected amongst all four groups. Highly significant positive correlations were recorded between genus-level microbiome and metabolomics data in tissue and feces. And several metabolites were associated with paired microbes, suggesting a strong microbiota-metabolome coupling, indicating also that part of the CRC metabolomic signature was attributable to microbes. Suggesting utility as potential biomarkers, most such microbiome and metabolites showed directionally consistent changes in CRC patients. Nevertheless, further studies are needed to increase sample sizes towards verifying these findings.
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Affiliation(s)
- Jiahui Feng
- School of Life Sciences, Anhui Medical University, Hefei, China
| | - Zhizhong Gong
- School of Life Sciences, Anhui Medical University, Hefei, China
| | - Zhangran Sun
- School of Life Sciences, Anhui Medical University, Hefei, China
- Henan International Joint Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial Key Laboratory of Long Non-coding RNA and Cancer Metabolism, Translational Research Institute of Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Juan Li
- Department of Oncology, BinHu Hospital of Hefei, Hefei, China
| | - Na Xu
- School of Life Sciences, Anhui Medical University, Hefei, China
| | - Rick F. Thorne
- Henan International Joint Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial Key Laboratory of Long Non-coding RNA and Cancer Metabolism, Translational Research Institute of Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China
- School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia
| | - Xu Dong Zhang
- Henan International Joint Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial Key Laboratory of Long Non-coding RNA and Cancer Metabolism, Translational Research Institute of Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China
- School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia
| | - Xiaoying Liu
- School of Life Sciences, Anhui Medical University, Hefei, China
- Henan International Joint Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial Key Laboratory of Long Non-coding RNA and Cancer Metabolism, Translational Research Institute of Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Gang Liu
- School of Life Sciences, Anhui Medical University, Hefei, China
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21
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Wang X, Zhu X, Li X, Li Z, Mao Y, Zhang S, Liu X, Liu X, Liu Y, Cao F, Zhang J. Transcriptomic and metabolomic analyses provide insights into the attenuation of neuroinflammation by nervonic acid in MPTP-stimulated PD model mice. Food Funct 2023; 14:277-291. [PMID: 36484706 DOI: 10.1039/d2fo02595g] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Nervonic acid is one of the most promising bioactive fatty acids, which is believed to be beneficial for the recovery of human cognitive disorders. However, the detailed neuroprotective effects and mode of action of nervonic acid have not yet been fully elucidated. In this study, we used an MPTP-stimulated mouse Parkinson's disease (PD) model as a target to investigate the neuroprotective effects by behavioral tests and integrative analysis of trancriptomes and metabolomes of PD mouse brain with nervonic acid injections. The KEGG pathway enrichment analysis of transcriptomes showed that the genes involved in neuroinflammation were significantly increased after MPTP induction and have been greatly inhibited by nervonic acid injection, while nervonic acid also greatly improved nerve growth and synaptic plasticity pathways which were significantly downregulated by MPTP. At the same time, the upregulation of oleic acid and arachidonic acid metabolism pathways and the downregulation of amino acid metabolism pathways in metabolomes were particularly highlighted in the nervonic acid protection groups compared with the PD model. Meanwhile, it was found that arachidonic acid, oleic acid and taurine play an important regulatory role in the neuroprotective mechanism of nervonic acid through fatty acid metabolism by integrative analysis. Therefore, our study laid a solid foundation for further studies on the specific role of nervonic acid in the inhibition of PD at the level of metabolic regulation.
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Affiliation(s)
- Xueqi Wang
- College of Life Science, Northwest Normal University, Lanzhou 730070, Gansu Province, China.
| | - Xinliang Zhu
- College of Life Science, Northwest Normal University, Lanzhou 730070, Gansu Province, China. .,Bioactive Products Engineering Research Center for Gansu Distinctive Plants, Lanzhou 730070, China.,Institute of Rural Development and Research, Northwest Normal University, Lanzhou 730070, Gansu Province, China.
| | - Xu Li
- College of Life Science, Northwest Normal University, Lanzhou 730070, Gansu Province, China.
| | - Zhengdou Li
- College of Life Science, Northwest Normal University, Lanzhou 730070, Gansu Province, China.
| | - Ying Mao
- College of Life Science, Northwest Normal University, Lanzhou 730070, Gansu Province, China.
| | - Shunbin Zhang
- College of Life Science, Northwest Normal University, Lanzhou 730070, Gansu Province, China.
| | - Xiaoxiao Liu
- Lanzhou Institute of Food and Drug Control, Lanzhou 740050, China.
| | - Xingguo Liu
- Lanzhou Institute of Food and Drug Control, Lanzhou 740050, China.
| | - Yapeng Liu
- Lanzhou Institute of Food and Drug Control, Lanzhou 740050, China.
| | - Fuliang Cao
- Nanjing Forestry University, Nanjing 210037, Jiangsu Province, China.
| | - Ji Zhang
- College of Life Science, Northwest Normal University, Lanzhou 730070, Gansu Province, China. .,Bioactive Products Engineering Research Center for Gansu Distinctive Plants, Lanzhou 730070, China.,Institute of Rural Development and Research, Northwest Normal University, Lanzhou 730070, Gansu Province, China.
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22
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Liu J, Zhou Y, Liu H, Ma M, Wang F, Liu C, Yuan Q, Wang H, Hou X, Yin P. Metabolic reprogramming enables the auxiliary diagnosis of breast cancer by automated breast volume scanner. Front Oncol 2022; 12:939606. [PMCID: PMC9597368 DOI: 10.3389/fonc.2022.939606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 09/15/2022] [Indexed: 12/24/2022] Open
Abstract
Breast cancer is the leading cause of female cancer-related deaths worldwide. New technologies with enhanced sensitivity and specificity for early diagnosis and monitoring of postoperative recurrence are in critical demand. Automatic breast full volume scanning system (ABVS) is an emerging technology used as an alternative imaging method for breast cancer screening. Despite its improved detection rate of malignant tumors, ABVS cannot accurately stage breast cancer preoperatively in 30–40% of cases. As a major hallmark of breast cancer, the characteristic metabolic reprogramming may provide potential biomarkers as an auxiliary method for ABVS.ObjectiveThe objective of this study was to identify differential metabolomic signatures between benign and malignant breast tumors and among different subtypes of breast cancer patients based on untargeted metabolomics and improve breast cancer detection rate by combining key metabolites and ABVS.MethodsUntargeted metabolomics approach was used to profile serum samples from 70 patients with different subtypes of breast cancer and benign breast tumor to determine specific metabolomic profiles through univariate and multivariate statistical data analysis.ResultsMetabolic profiles correctly distinguished benign and malignant breast tumors patients, and a total of 791 metabolites were identified. There were 54 different metabolites between benign and malignant breast tumors and 17 different metabolites between invasive and non-invasive breast cancer. Notably, the missed diagnosis rate of ABVS could be reduced by differential metabolite analysis. Moreover, the diagnostic performance analyses of combined metabolites (pelargonic acid, N-acetylasparagine, and cysteine-S-sulfate) with ABVS performance gave a ROC area under the curve of 0.967 (95% CI: 0.926, 0.993).ConclusionsOur study identified metabolic features both in benign and malignant breast tumors and in invasive and non-invasive breast cancer. Combined ultrasound ABVS and a panel of differential serum metabolites could further improve the accuracy of preoperative diagnosis of breast cancer and guide surgical therapy.
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Affiliation(s)
- Jianjun Liu
- Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- College of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Yang Zhou
- Department of Ultrasound, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Huiying Liu
- Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- College of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Mengyan Ma
- Department of Ultrasound, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Fei Wang
- Breast Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Chang Liu
- Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- College of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Qihang Yuan
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Hongjiang Wang
- Breast Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Xiukun Hou
- Department of Ultrasound, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- *Correspondence: Peiyuan Yin, ; Xiukun Hou,
| | - Peiyuan Yin
- Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- College of Integrative Medicine, Dalian Medical University, Dalian, China
- *Correspondence: Peiyuan Yin, ; Xiukun Hou,
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23
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Ni Z, Xu S, Yu Z, Ye Z, Li R, Chen C, Yang J, Liu H, Zhou Z, Zhang X. Comparison of dual mTORC1/2 inhibitor AZD8055 and mTORC1 inhibitor rapamycin on the metabolism of breast cancer cells using proton nuclear magnetic resonance spectroscopy metabolomics. Invest New Drugs 2022; 40:1206-1215. [PMID: 36063263 DOI: 10.1007/s10637-022-01268-w] [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: 05/02/2022] [Accepted: 06/06/2022] [Indexed: 11/28/2022]
Abstract
Dual mTORC1/2 inhibitors may be more effective than mTORC1 inhibitor rapamycin. Nevertheless, their metabolic effects on breast cancer cells have not been reported. We compared the anti-proliferative capacity of rapamycin and a novel mTORC1/2 dual inhibitor (AZD8055) in two breast cancer cell lines (MDA-MB-231 and MDA-MB-453) and analyzed their metabolic effects using proton nuclear magnetic resonance (1H NMR) spectroscopy-based metabolomics. We found that AZD8055 more strongly inhibited breast cancer cell proliferation than rapamycin. The half-inhibitory concentration of AZD8055 in breast cancer cells was almost one-tenth that of rapamycin. We identified 22 and 23 metabolites from the 1H NMR spectra of MDA-MB-231 and MDA-MB-453 cells. The patterns of AZD8055- and rapamycin-treated breast cancer cells differed significantly; we then selected the metabolites that contributed to these differences. For inhibiting glycolysis and reducing glucose consumption, AZD8055 was likely to be more potent than rapamycin. For amino acids metabolism, although AZD8055 has a broad effect as rapamycin, their effects in degrees were not exactly the same. AZD8055 and rapamycin displayed cell-specific metabolic effects on breast cancer cells, a finding that deserves further study. These findings help fill the knowledge gap concerning dual mTORC1/2 inhibitors and provide a theoretical basis for their development.
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Affiliation(s)
- Zhitao Ni
- Clinical Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Shaolin Xu
- Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zheng Yu
- Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zhongjiang Ye
- Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Rongqi Li
- Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Chuang Chen
- Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jianhui Yang
- Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Huamin Liu
- College of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Ziye Zhou
- Clinical Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
| | - Xiuhua Zhang
- Clinical Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
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24
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Yousuf M, Shamsi A, Mohammad T, Azum N, Alfaifi SYM, Asiri AM, Mohamed Elasbali A, Islam A, Hassan MI, Haque QMR. Inhibiting Cyclin-Dependent Kinase 6 by Taurine: Implications in Anticancer Therapeutics. ACS OMEGA 2022; 7:25844-25852. [PMID: 35910117 PMCID: PMC9330843 DOI: 10.1021/acsomega.2c03479] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 07/04/2022] [Indexed: 06/15/2023]
Abstract
Cyclin-dependent kinase 6 (CDK6) is linked with a cyclin partner and plays a crucial role in the early stages of cancer development. It is currently a potential drug target for developing therapeutic molecules targeting cancer therapy. Here, we have identified taurine as an inhibitor of CDK6 using combined in silico and experimental studies. We performed various experiments to find the binding affinity of taurine with CDK6. Molecular docking analysis revealed critical residues of CDK6 that are involved in taurine binding. Fluorescence measurement studies showed that taurine binds to CDK6 with a significant binding affinity, with a binding constant of K = 0.7 × 107 M-1 for the CDK6-taurine complex. Enzyme inhibition assay suggested taurine as a good inhibitor of CDK6 possessing an IC50 value of 4.44 μM. Isothermal titration calorimetry analysis further confirmed a spontaneous binding of taurine with CDK6 and delineated the thermodynamic parameters for the CDK6-taurine system. Altogether, this study established taurine as a CDK6 inhibitor, providing a base for using taurine and its derivatives in CDK6-associated cancer and other diseases.
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Affiliation(s)
- Mohd Yousuf
- Department
of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Anas Shamsi
- Centre
for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
- Centre
of
Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
| | - Taj Mohammad
- Centre
for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Naved Azum
- Center
of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Chemistry
Department, Faculty of Science, King Abdulaziz
University, Jeddah 21589, Saudi Arabia
| | - Sulaiman Y. M. Alfaifi
- Chemistry
Department, Faculty of Science, King Abdulaziz
University, Jeddah 21589, Saudi Arabia
| | - Abdullah M. Asiri
- Center
of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Chemistry
Department, Faculty of Science, King Abdulaziz
University, Jeddah 21589, Saudi Arabia
| | - Abdelbaset Mohamed Elasbali
- Clinical
Laboratory Science, College of Applied Sciences-Qurayyat, Jouf University, Sakaka 72388, Saudi Arabia
| | - Asimul Islam
- Centre
for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Md Imtaiyaz Hassan
- Centre
for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
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25
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Barnett JD, Jin J, Penet MF, Kobayashi H, Bhujwalla ZM. Phototheranostics of Splenic Myeloid-Derived Suppressor Cells and Its Impact on Spleen Metabolism in Tumor-Bearing Mice. Cancers (Basel) 2022; 14:cancers14153578. [PMID: 35892836 PMCID: PMC9332589 DOI: 10.3390/cancers14153578] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/15/2022] [Accepted: 07/21/2022] [Indexed: 02/04/2023] Open
Abstract
(1) Background: MDSCs play an active role in the immune surveillance escape of cancer cells. Because MDSCs in mice are CD11b+Gr1+, near-infrared photoimmunotherapy (NIR-PIT) using the NIR dye IR700 conjugated to an MDSC-binding antibody provides an opportunity for targeted elimination of MDSCs. (2) Methods: The efficacy of Gr1-IR700-mediated NIR-PIT was evaluated in vitro using magnetically separated CD11b+Gr1+ MDSCs from spleens of 4T1-luc tumor-bearing (TB) mice. For in vivo evaluation, spleens of Gr1-IR700-injected 4T1-luc TB mice were irradiated with NIR light, and splenocyte viability was determined using CCK-8 assays. Metabolic profiling of NIR-PIT-irradiated spleens was performed using 1H MRS. (3) Results: Flow cytometric analysis confirmed a ten-fold increase in splenic MDSCs in 4T1-luc TB mice. Gr1-IR700-mediated NIR-PIT eliminated tumor-induced splenic MDSCs in culture. Ex vivo fluorescence imaging revealed an 8- and 9-fold increase in mean fluorescence intensity (MFI) in the spleen and lungs of Gr1-IR700-injected compared to IgG-IR700-injected TB mice. Splenocytes from Gr1-IR700-injected TB mice exposed in vivo to NIR-PIT demonstrated significantly lower viability compared to no light exposure or untreated control groups. Significant metabolic changes were observed in spleens following NIR-PIT. (4) Conclusions: Our data confirm the ability of NIR-PIT to eliminate splenic MDSCs, identifying its potential to eliminate MDSCs in tumors to reduce immune suppression. The metabolic changes observed may identify potential biomarkers of splenic MDSC depletion as well as potential metabolic targets of MDSCs.
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Affiliation(s)
- James D. Barnett
- Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (J.D.B.); (J.J.); (M.-F.P.)
| | - Jiefu Jin
- Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (J.D.B.); (J.J.); (M.-F.P.)
| | - Marie-France Penet
- Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (J.D.B.); (J.J.); (M.-F.P.)
- Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Hisataka Kobayashi
- Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, MD 20814, USA;
| | - Zaver M. Bhujwalla
- Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (J.D.B.); (J.J.); (M.-F.P.)
- Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Correspondence:
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26
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Zhuang J, Yang X, Zheng Q, Li K, Cai L, Yu H, Lv J, Bai K, Cao Q, Li P, Yang H, Wang J, Lu Q. Metabolic Profiling of Bladder Cancer Patients' Serum Reveals Their Sensitivity to Neoadjuvant Chemotherapy. Metabolites 2022; 12:metabo12060558. [PMID: 35736490 PMCID: PMC9229374 DOI: 10.3390/metabo12060558] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/07/2022] [Accepted: 06/13/2022] [Indexed: 02/07/2023] Open
Abstract
Numerous patients with muscle-invasive bladder cancer develop low responsiveness to cisplatin. Our purpose was to explore differential metabolites derived from serum in bladder cancer patients treated with neoadjuvant chemotherapy (NAC). Data of patients diagnosed with cT2-4aNxM0 was collected. Blood samples were retained prospectively before the first chemotherapy for untargeted metabolomics by 1H-NMR and UPLC-MS. To identify characterized metabolites, multivariate statistical analyses were applied, and the intersection of the differential metabolites discovered by the two approaches was used to identify viable biomarkers. A total of 18 patients (6 NAC-sensitive patients and 12 NAC-resistant patients) were enrolled. There were 29 metabolites detected by 1H-NMR and 147 metabolites identified by UPLC-MS. Multivariate statistics demonstrated that in the sensitive group, glutamine and taurine were considerably increased compared to their levels in the resistant group, while glutamate and hypoxanthine were remarkably decreased. Pathway analysis and enrichment analysis showed significant alterations in amino acid pathways, suggesting that response to chemotherapy may be related to amino acid metabolism. In addition, hallmark analysis showed that DNA repair played a regulatory role. Overall, serum metabolic profiles of NAC sensitivity are significantly different in bladder cancer patients. Glycine, hypoxanthine, taurine and glutamine may be the potential biomarkers for clinical treatment. Amino acid metabolism has potential value in enhancing drug efficacy.
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Affiliation(s)
- Juntao Zhuang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; (J.Z.); (X.Y.); (K.L.); (L.C.); (H.Y.); (J.L.); (K.B.); (Q.C.); (P.L.); (H.Y.)
| | - Xiao Yang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; (J.Z.); (X.Y.); (K.L.); (L.C.); (H.Y.); (J.L.); (K.B.); (Q.C.); (P.L.); (H.Y.)
| | - Qi Zheng
- Center of Molecular Metabolism, Nanjing University of Science and Technology, Nanjing 210094, China;
| | - Kai Li
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; (J.Z.); (X.Y.); (K.L.); (L.C.); (H.Y.); (J.L.); (K.B.); (Q.C.); (P.L.); (H.Y.)
| | - Lingkai Cai
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; (J.Z.); (X.Y.); (K.L.); (L.C.); (H.Y.); (J.L.); (K.B.); (Q.C.); (P.L.); (H.Y.)
| | - Hao Yu
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; (J.Z.); (X.Y.); (K.L.); (L.C.); (H.Y.); (J.L.); (K.B.); (Q.C.); (P.L.); (H.Y.)
| | - Jiancheng Lv
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; (J.Z.); (X.Y.); (K.L.); (L.C.); (H.Y.); (J.L.); (K.B.); (Q.C.); (P.L.); (H.Y.)
| | - Kexin Bai
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; (J.Z.); (X.Y.); (K.L.); (L.C.); (H.Y.); (J.L.); (K.B.); (Q.C.); (P.L.); (H.Y.)
| | - Qiang Cao
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; (J.Z.); (X.Y.); (K.L.); (L.C.); (H.Y.); (J.L.); (K.B.); (Q.C.); (P.L.); (H.Y.)
| | - Pengchao Li
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; (J.Z.); (X.Y.); (K.L.); (L.C.); (H.Y.); (J.L.); (K.B.); (Q.C.); (P.L.); (H.Y.)
| | - Haiwei Yang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; (J.Z.); (X.Y.); (K.L.); (L.C.); (H.Y.); (J.L.); (K.B.); (Q.C.); (P.L.); (H.Y.)
| | - Junsong Wang
- Center of Molecular Metabolism, Nanjing University of Science and Technology, Nanjing 210094, China;
- Correspondence: (J.W.); (Q.L.)
| | - Qiang Lu
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; (J.Z.); (X.Y.); (K.L.); (L.C.); (H.Y.); (J.L.); (K.B.); (Q.C.); (P.L.); (H.Y.)
- Correspondence: (J.W.); (Q.L.)
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Chen W, Li Q, Hou R, Liang H, Zhang Y, Yang Y. An integrated metabonomics study to reveal the inhibitory effect and metabolism regulation of taurine on breast cancer. J Pharm Biomed Anal 2022; 214:114711. [PMID: 35306435 DOI: 10.1016/j.jpba.2022.114711] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 02/22/2022] [Accepted: 03/03/2022] [Indexed: 12/23/2022]
Abstract
Breast cancer is a common metastatic malignant tumor in women. Taurine has been found to have anti-tumor effects on a variety of cancers. However, to the best of our knowledge, the role of taurine in the metastasis of breast cancer has not been reported. Thus, this study examined the effects of taurine on the growth and lung metastasis of breast cancer. Furthermore, the metabolism of serum, tumor tissue, and lung metastasis tissue were studied in a 4T1 subcutaneously transplanted breast cancer model through the integration of a 1H NMR-based metabonomics approach and histopathological assessments. The results showed that taurine significantly attenuated the tumor growth and lung metastasis, improved the pathological structure of tumor and lung tissue, and improved the metabolic disorders in 4T1 breast cancer mice. Additionally, taurine reversed the changes in serum lactate, creatine, and choline caused by the progression of breast cancer tumors. The levels of leucine/isoleucine, valine, alanine, arginine, methionine, glutamate, histidine, trimethylamine oxide (TMAO), taurine, and glucose in tumor tissues decreased, with an increment in lipids, lactate, and N-acetyl glycoprotein. Also, there was a reversal of leucine/isoleucine, valine, lactate, arginine, N-acetyl glycoprotein, glutamate, histidine, choline, and glycerophosphocholine/phosphocholine (GPC/PC) in the lung tissues. These metabolites changes were involved in the metabolic pathways of glycolysis, choline, amino acid, and lipid, suggesting that taurine exerted anti-breast cancer effects through the regulation of the underlying metabolism. This study provides a scientific basis for the adoption of taurine in the treatment of breast cancer metastasis.
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Affiliation(s)
| | - Qian Li
- College of Life Sciences and Biopharmaceuticals, PR China
| | | | - Huaguo Liang
- College of Life Sciences and Biopharmaceuticals, PR China
| | - Yongli Zhang
- College of Life Sciences and Biopharmaceuticals, PR China.
| | - Yongxia Yang
- College of Medical Information Engineering, Guangdong Pharmaceutical University, Guangzhou 510006, PR China; Guangdong Province Key Laboratory for Biotechnology Drug Candidates, PR China.
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Li X, Liu L, Li N, Jia Q, Wang X, Zuo L, Long J, Xue P, Sun Z, Zhao H. Metabolomics based plasma biomarkers for diagnosis of oral squamous cell carcinoma and oral erosive lichen planus. J Cancer 2022; 13:76-87. [PMID: 34976172 PMCID: PMC8692701 DOI: 10.7150/jca.59777] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 11/02/2021] [Indexed: 11/05/2022] Open
Abstract
Backgrounds: To identify diagnostic biomarkers for differentiating oral squamous cell carcinoma (OSCC) from oral erosive lichen planus (OELP) and investigate potential biomarkers associated with malignant transformation. Methods: In this study, 72 patients with OSCC, 75 patients with OELP subjects were recruited. Their plasma samples were analyzed by ultra-high-performance liquid chromatography quadrupole-Orbitrap high-resolution accurate mass spectrometry, (UHPLC/Q-Orbitrap HRMS). Principal component analysis, orthogonal partial least square discrimination analysis, t-test analysis and false discovery rate were used to identify different metabolites in patients with OSCC and OELP. The metabolic pathway analysis was performed by MetaboAnalyst. To further screen and identify the biomarkers of OSCC and establish a diagnostic panel, binary logistic regression analysis and receiver operating characteristic analysis were used. The data were then combined with blood samples from healthy individuals for mass spectrometry analysis to obtain biomarkers related to malignant transformation. Results: A total of 20 kinds of endogenous metabolites were identified from plasma samples of OSCC patients and OELP patients. Metabolic pathway analysis showed that the biomarkers associated with OSCC were closely related to cholic acid metabolism and amino acid metabolism. Finally, a diagnostic panel composed of decanoylcarnitine, cysteine and cholic acid was established. This diagnostic panel had good diagnostic efficiency with the AUC=0.998. Other metabolites including uridine, taurine, glutamate, citric acid and LysoPC(18:1) were identified to be general biomarkers for malignant transformation of OELP. Conclusion: Biomarkers based on plasma metabolomics are of great significance for the prediction of malignant transformation of OELP and early diagnosis of OSCC.
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Affiliation(s)
- Xibo Li
- Department of Oral Emergency, The First Affiliated Hospital of Zhengzhou University· Stomatological Hospital of Henan Province, Zhengzhou, Henan, 450052, China.,School and Hospital of Stomatology of Zhengzhou University, Zhengzhou, Henan, 450052, China
| | - Liwei Liu
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.,Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, Henan, 450052, China
| | - Na Li
- Department of Prosthodontics, The First Affiliated Hospital of Zhengzhou University· Stomatological Hospital of Henan Province, Zhengzhou, Henan, 450052, China
| | - Qingquan Jia
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.,Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, Henan, 450052, China
| | - Xiaoshuang Wang
- Department of Oral Emergency, The First Affiliated Hospital of Zhengzhou University· Stomatological Hospital of Henan Province, Zhengzhou, Henan, 450052, China.,School and Hospital of Stomatology of Zhengzhou University, Zhengzhou, Henan, 450052, China
| | - Lihua Zuo
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.,Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, Henan, 450052, China
| | - Jianglan Long
- Beijing Key Laboratory and Joint Laboratory for International Cooperation of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038, China
| | - Peng Xue
- Health Management Center, The First Affiliated Hospital of Zhengzhou University· Stomatological Hospital of Henan Province, Zhengzhou, Henan, 450052, China
| | - Zhi Sun
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.,Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, Henan, 450052, China
| | - Hongyu Zhao
- Department of Oral Emergency, The First Affiliated Hospital of Zhengzhou University· Stomatological Hospital of Henan Province, Zhengzhou, Henan, 450052, China.,School and Hospital of Stomatology of Zhengzhou University, Zhengzhou, Henan, 450052, China
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29
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Ma J, Yang Z, Jia S, Yang R. A systematic review of preclinical studies on the taurine role during diabetic nephropathy: focused on anti-oxidative, anti-inflammation, and anti-apoptotic effects. Toxicol Mech Methods 2022; 32:420-430. [PMID: 34933643 DOI: 10.1080/15376516.2021.2021579] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Diabetic nephropathy is one of the most important and growing diseases globally and the leading cause of cardiovascular mortality in these patients. Taurine is an amino acid that has pleiotropic protective properties on some diseases. This study aimed to investigate the potential role of taurine in the treatment of diabetes-induced nephropathy. To achieve the aim of the present study, a comprehensive systematic search based on PRISMA guidelines has been conducted up to August 2021. A total of 382 articles were found in the electronic databases based on search keywords. After doing the screening, 14 articles were included in the present systematic review. The dated demonstrated elevation of oxidative stress, inflammatory and apoptotic pathways, and changes in other molecules' function plays an essential role in diabetes-induced renal tissue damage. Due to its multiple protective effects, taurine significantly prevented the activation of the pathways mentioned above and altered the function of molecules involved in these pathways, resulting in alleviating diabetic nephropathy. According to the obtained results, it was found that taurine can mitigate diabetes-induced nephropathy, mainly through its anti-oxidant activity, which is an essential factor in activating inflammation and apoptosis pathways.
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Affiliation(s)
- Jingru Ma
- Clinical Laboratory, The Second Hospital of Jilin University, Changchun, China
| | - Zecheng Yang
- Department of Gastrointestinal Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Shengnan Jia
- Department of Hepatopancreatobiliary Medicine, The Second Hospital of Jilin University, Changchun, China
| | - Rui Yang
- Department of Gastroenterology, The Second Hospital of Jilin University, Changchun, China
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30
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Current Opinion on the Therapeutic Capacity of Taurine-Containing Halogen Derivatives in Infectious and Inflammatory Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1370:83-98. [PMID: 35882784 DOI: 10.1007/978-3-030-93337-1_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
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31
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Mock-Ohnesorge J, Mock A, Hackert T, Fröhling S, Schenz J, Poschet G, Jäger D, Büchler MW, Uhle F, Weigand MA. Perioperative changes in the plasma metabolome of patients receiving general anesthesia for pancreatic cancer surgery. Oncotarget 2021; 12:996-1010. [PMID: 34012512 PMCID: PMC8121611 DOI: 10.18632/oncotarget.27956] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 04/19/2021] [Indexed: 02/07/2023] Open
Abstract
Background: Modern anesthesia strives to offer personalized concepts to meet the patient’s individual needs in sight of clinical outcome. Still, little is known about the impact of anesthesia on the plasma metabolome, although many metabolites have been shown to modulate the function of various immune cells, making it particularly interesting in the context of oncological surgery. In this study longitudinal dynamics in the plasma metabolome during general anesthesia in patients undergoing pancreatic surgery were analyzed. Materials and Methods: Prospective, observational study with 10 patients diagnosed with pancreatic (pre-) malignancy and subjected to elective resection surgery under general anesthesia. Plasma metabolites (n = 630) were quantified at eight consecutive perioperative timepoints using mass spectrometry-based targeted metabolomics. Results: 39 metabolites significantly changed during the perioperative period. Tryptophan concentrations decreased by 45% with the maximum decrease after anesthesia induction (p = 6.24E-07), while taurine synthesis increased (p = 1.46E-04). Triacylglycerides and lysophosphatidylcholines were significantly reduced with increased liberation of free monounsaturated fatty acids (p = 0.03). Carnitine levels decreased significantly (p = 9.30E-04). Conclusions: The major finding of this study was perioperative tryptophan depletion and increased taurine synthesis. Both are essential for immune cell function and are therefore of significant interest for perioperative management. Further studies are needed to identify influencing anesthetic factors.
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Affiliation(s)
| | - Andreas Mock
- Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg University Hospital, Heidelberg, Germany.,Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.,German Cancer Consortium (DKTK), Heidelberg, Germany
| | - Thilo Hackert
- Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Stefan Fröhling
- Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.,German Cancer Consortium (DKTK), Heidelberg, Germany
| | - Judith Schenz
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Gernot Poschet
- Centre for Organismal Studies (COS), University of Heidelberg, Heidelberg, Germany
| | - Dirk Jäger
- Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg University Hospital, Heidelberg, Germany.,German Cancer Consortium (DKTK), Heidelberg, Germany
| | - Markus W Büchler
- Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Florian Uhle
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Markus A Weigand
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
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32
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Baliou S, Sofopoulos M, Goulielmaki M, Spandidos DA, Ioannou P, Kyriakopoulos AM, Zoumpourlis V. Bromamine T, a stable active bromine compound, prevents the LPS‑induced inflammatory response. Int J Mol Med 2021; 47:37. [PMID: 33537817 PMCID: PMC7891821 DOI: 10.3892/ijmm.2021.4870] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 01/26/2021] [Indexed: 12/28/2022] Open
Abstract
Inflammation is the most common cause of most acute and chronic debilitating diseases. Towards unveiling novel therapeutic options for patients with such complications, N‑bromotaurine (TauNHBr) has emerged as a potential anti‑inflammatory agent; however, its therapeutic efficacy is hindered due to its relatively poor stability. To address this challenge, the present study focused on examining the effects of a stable active bromine compound, named bromamine T (BAT). The present study examined the protective properties of BAT against lipopolysaccharide (LPS)‑mediated inflammation in vitro, by using LPS‑stimulated murine J774.A1 macrophages (Mφs), as well as in vivo, by using a murine LPS‑mediated air‑pouch model. Additionally, its efficacy was compared with that of taurine, a known potent anti‑inflammatory molecule. In LPS‑stimulated J774A.1 Mφs, BAT and taurine were very effective in reducing the secretion of pro‑inflammatory mediators. The in vitro experiments indicated that LPS‑mediated inflammation was attenuated due to the protective properties of BAT and of taurine, probably through the inhibition of phosphorylated p65 NF‑κB subunit (Ser 536) nuclear translocation. The in vivo experiments also revealed that BAT and taurine inhibited LPS‑mediated inflammation by reducing total cell/polymorphonuclear cell (PMN) infiltration in the air‑pouch and by decreasing pouch wall thickness. The analysis of exudates obtained from pouches highlighted that the inhibitory effects of BAT and taurine on the secretion of pro‑inflammatory cytokines were similar to those observed in vitro. Notably, the effect of BAT at the highest concentration tested was superior to that of taurine at the highest concentration. Taken together, the findings of the present study indicate that BAT prevents the LPS‑induced inflammatory response both in vitro and in vivo.
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Affiliation(s)
- Stella Baliou
- National Hellenic Research Foundation, 11635 Athens, Greece
| | - Michael Sofopoulos
- Department of Surgical Pathology, Saint Savvas Anticancer Hospital of Athens, 11522 Athens, Greece
| | | | - Demetrios A. Spandidos
- Laboratory of Clinical Virology, Medical School, University of Crete, 71003 Heraklion, Greece
| | - Petros Ioannou
- Department of Internal Medicine and Infectious Diseases, University Hospital of Heraklion, 71110 Heraklion, Greece
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