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1
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Shi H, Yang SA, Bai LY, Du JJ, Wu Z, He ZH, Liu H, Cui JY, Zhao M. Mechanism of myocardial damage induced by doxorubicin via calumenin-regulated mitochondrial dynamics and the calcium–Cx43 pathway. World J Cardiol 2025; 17:104839. [DOI: 10.4330/wjc.v17.i5.104839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 04/01/2025] [Accepted: 05/07/2025] [Indexed: 05/23/2025] Open
Abstract
BACKGROUND The clinical application of doxorubicin (DOX) is limited by its potential to cause cardiac cardiotoxicity.
AIM To investigate the correlation between calumenin (CALU) and mitochondrial kinetic-related proteins in rats with DOX cardiomyopathy.
METHODS A rat model of DOX-induced cardiomyopathy was used to evaluate the effects of DOX. We observed the effect of DOX on electrical conduction in cardiomyocytes using the electromapping technique. Masson staining was performed to evaluate myocardium fibrosis. Electron microscopy was used to observe the changes in pathological ultrastructure of the myocardium. Western blotting and ELISAs were performed to detect protein levels and intracellular free Ca2+ concentration.
RESULTS DOX slowed conduction and increased conduction dispersion in cardiomyocytes. The myocardial pathology in rats treated with DOX exhibited a significant deterioration, as demonstrated by an increase in mitochondrial Ca2+ concentration and a decrease in the expression of CALU, optic atrophy-1, and Bcl-2. Additionally, there was an increase in the expression of connexin 43 (Cx43) and the mitochondrial mitotic proteins dynamin-related protein 1, CHOP, Cytochrome C, and Bax in DOX rats. Decreased expression of CALU in cardiomyocytes triggered an increase in cytoplasmic free calcium concentration, which would normally be taken up by mitochondria, but decreased expression of mitochondrial outer membrane fusion proteins triggered a decrease in mitochondrial Ca2+ uptake, and the increase in cytoplasmic free calcium concentration triggered cell apoptosis.
CONCLUSION Increased cytoplasmic free calcium ion concentration induces calcium overload in ventricular myocytes, leading to decreased Cx43 protein, slowed conduction in myocytes, and increased conduction dispersion, resulting in arrhythmias.
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Affiliation(s)
- He Shi
- Department of Cardiovascular Medicine, Affiliated Hospital of Beihua University, Jilin Province 132000, China
| | - Song-Ao Yang
- Department of Biological Sciences, Inner Mongolia Minzu University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Ling-Yu Bai
- Department of Cardiovascular Medicine, Affiliated Hospital of Inner Mongolia Minzu University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Jian-Jun Du
- Department of Cardiovascular Medicine, The First People's Hospital of Horqin District, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Zhe Wu
- Department of Cardiovascular Medicine, Tongliao Municipal Hospital, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Zhi-Hui He
- Department of Human Anatomy, Histology and Embryology, Inner Mongolia Minzu University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Hao Liu
- Section of Anatomy, Inner Mongolia Minzu University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Jia-Yue Cui
- College of Basic Medical Sciences, Jilin University, Changchun 130000, Jilin Province, China
| | - Ming Zhao
- Department of Cardiovascular Medicine, Affiliated Hospital of Inner Mongolia Minzu University, Tongliao 028000, Inner Mongolia Autonomous Region, China
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Pandey AK, Ezewudo E, Hoque N, Pandey AT, Menon S, Simon N, Rasouli B, Habibi E, Sarker SD, Nahar L, Hasan R. A review of food hydrocolloids on cardiovascular health: Alginate, astragalus polysaccharides, carrageenan, fucoidan, lunasin, and psyllium. Int J Biol Macromol 2025; 315:144505. [PMID: 40409656 DOI: 10.1016/j.ijbiomac.2025.144505] [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: 04/06/2025] [Revised: 05/06/2025] [Accepted: 05/20/2025] [Indexed: 05/25/2025]
Abstract
Food hydrocolloids, derived from natural sources such as plants, algae, and microbes, possess bioactive properties that significantly contribute to cardiovascular health. This review focuses on six key hydrocolloids: alginate, astragalus polysaccharides, carrageenan, fucoidan, lunasin, and psyllium, while also considering other important natural hydrocoloids such as short chain fatty acids (SCFAs), plant-derived food hydrocolloids, plant-derived gums, plant-derived mucilages, pectin, modified citrus pectin, inulin, naringenin, chia seeds, gelatine, whey protein, casein, microbial exopolysaccharides and gums, ulvan, and laminarin. Alginate, from brown seaweed, aids in cardiac tissue regeneration and repair. Astragalus polysaccharides, from the Astragalus plant, provide antioxidant, anti-inflammatory, and immunomodulatory benefits. Carrageenan, sourced from red seaweed, supports lipid profile balance and heart health. Fucoidan, another brown seaweed derivative, offers antihypertensive and lipid-lowering effects. Lunasin, a peptide found in soybeans, oats, and barley, is known for its cholesterol-lowering properties and anti-inflammatory effects. Psyllium, rich in soluble fiber, helps lower LDL cholesterol and improve overall cardiovascular function. These hydrocolloids, along with other mentioned compounds, are utilized in drug formulations, cosmetics, processed foods, and dietary supplements, enhancing food texture and stability while delivering health benefits. Upon consumption, they can be absorbed into the bloodstream or metabolized by gut microbiota into bioactive metabolites. This review examines their effects on cardiovascular function, highlighting their mechanisms in regulating vascular tone, blood pressure, vascular inflammation, and cardiac function. It consolidates current research, emphasizing the potential of these hydrocolloids and related compounds in the prevention and management of cardiovascular diseases (CVDs).
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Affiliation(s)
- Ajay K Pandey
- Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA, USA; Augusta University/University of Georgia Medical Partnership, University of Georgia Health Science Campus, Athens, GA, USA
| | - Emmanuella Ezewudo
- Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA, USA
| | - Nazia Hoque
- Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA, USA; Department of Pharmacy, East West University, Dhaka, Bangladesh
| | - Anjali T Pandey
- Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA, USA; Department of Psychology, St. Bonaventure University, St. Bonaventure, NY, USA
| | - Sreelakshmi Menon
- Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA, USA
| | - Nimi Simon
- Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA, USA
| | | | - Emran Habibi
- Medicinal Plants Research Centre, Institute of Herbal Medicines and Metabolic Disorders, Mazandaran University of Medical Sciences, Sari, Iran; Centre for Natural Products Discovery, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK
| | - Satyajit D Sarker
- Centre for Natural Products Discovery, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK
| | - Lutfun Nahar
- Laboratory of Growth Regulators, Palacký University and Institute of Experimental Botany, The Czech Academy of Sciences, Šlechtitelů 27, Olomouc, Czech Republic.
| | - Raquibul Hasan
- Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA, USA.
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3
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Ma X, Zhu K, Wang K, Liao W, Yang X, Yu W, Wang W, Han F. Improvement of Catalytic Activity and Thermostability of Alginate Lyase VxAly7B-CM via Rational Computational Design Strategies. Mar Drugs 2025; 23:198. [PMID: 40422788 DOI: 10.3390/md23050198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2025] [Revised: 04/26/2025] [Accepted: 04/26/2025] [Indexed: 05/28/2025] Open
Abstract
Alginate lyase degrades alginate through the β-elimination mechanism to produce alginate oligosaccharides (AOS) with notable biochemical properties and diverse biological activities. However, its poor thermostability limits large-scale industrial production. In this study, we employed a rational computational design strategy combining computer-aided evolutionary coupling analysis and ΔΔGfold evaluation to enhance both the thermostability and catalytic activity of the alginate lyase VxAly7B-CM. Among ten single-point mutants, the E188N and S204G mutants exhibited increases in Tm from 47.0 °C to 48.9 °C and 50.2 °C, respectively, with specific activities of 3701.02 U/mg and 2812.01 U/mg at 45 °C. Notably, the combinatorial mutant E188N/S204G demonstrated a ΔTm of 5 °C and an optimal reaction temperature up to 50 °C, where its specific activity reached 3823.80 U/mg-a 31% increase. Moreover, its half-life at 50 °C was 38.4 h, which is 7.0 times that of the wild-type enzyme. Protein structural analysis and molecular dynamics simulations suggested that the enhanced catalytic performance and thermostability of the E188N/S204G mutant may be attributed to optimized surface charge distribution, strengthened hydrophobic interactions, and increased tertiary structure stability. Overall, our findings provided valuable insights into enzyme stabilization strategies and supported the industrial production of functional AOS.
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Affiliation(s)
- Xin Ma
- School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China
- Key Laboratory of Marine Drugs, Ministry of Education, Qingdao 266003, China
- Shandong Key Laboratory of Glycoscience and Glycotherapeutics, Qingdao 266003, China
| | - Ke Zhu
- School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China
- Key Laboratory of Marine Drugs, Ministry of Education, Qingdao 266003, China
- Shandong Key Laboratory of Glycoscience and Glycotherapeutics, Qingdao 266003, China
| | - Kaiyang Wang
- School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China
- Key Laboratory of Marine Drugs, Ministry of Education, Qingdao 266003, China
- Shandong Key Laboratory of Glycoscience and Glycotherapeutics, Qingdao 266003, China
| | - Wenhui Liao
- School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China
- Key Laboratory of Marine Drugs, Ministry of Education, Qingdao 266003, China
- Shandong Key Laboratory of Glycoscience and Glycotherapeutics, Qingdao 266003, China
| | - Xiaohan Yang
- State Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Wengong Yu
- School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China
- Key Laboratory of Marine Drugs, Ministry of Education, Qingdao 266003, China
- Shandong Key Laboratory of Glycoscience and Glycotherapeutics, Qingdao 266003, China
| | - Weishan Wang
- School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- State Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Beijing Key Laboratory of Genetic Element Biosourcing & Intelligent Design for Biomanufacturing, Beijing 100101, China
| | - Feng Han
- School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China
- Key Laboratory of Marine Drugs, Ministry of Education, Qingdao 266003, China
- Shandong Key Laboratory of Glycoscience and Glycotherapeutics, Qingdao 266003, China
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Mohamed NA, Shouran NM, Essawy AE, Abdel-Moneim AM, Abdel Salam S. Mitigative effect of sodium alginate on streptozotocin (STZ)-induced diabetic neuropathy through regulation of redox status and miR-146a in the rat sciatic nerve. PeerJ 2025; 13:e19046. [PMID: 40151454 PMCID: PMC11949120 DOI: 10.7717/peerj.19046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 02/03/2025] [Indexed: 03/29/2025] Open
Abstract
Diabetic peripheral neuropathy (DPN) is a significant complication of diabetes with limited effective therapeutic options. Sodium alginate (SA), a natural polysaccharide from brown algae, has demonstrated health benefits, however, whether it can treat streptozotocin (STZ)-induced DPN remains unclear. The present experiment aimed to test the preventive role of SA on STZ-induced DPN in rats and explored the possible mechanisms. The DPN rat model was established in rats by intraperitoneal injection of a single dose of 40 mg/kg b.w. STZ, and SA (200 mg/kg b.w./day) was orally administered for 28 days after type 2 diabetes mellitus (T2DM) induction. The obtained findings revealed that STZ significantly increased serum levels of FBG, HOMA-IR, TC, TG, VLDL-C, and LDL-C, while decreased serum insulin, incretin GLP-1, HDL-C, and lipase activity. In the sciatic nerves, STZ significantly increased proinflammatory cytokine levels (IL-1β, IL-6, and TNF-α), caspase-3 (a pro-apoptotic protein), markers of oxidative stress (MDA and NO), and AGEs. In parallel, STZ induced a significant decline in the activities of enzymatic antioxidants, viz., SOD, CAT, and GPx, and non-enzymatic GSH. These changes were accompanied by a low expression of miR-146a in the sciatic nerves of DPN rats. Except for HOMA-IR, SA treatment to STZ injected rats significantly improved these parameters and helped to rescue the neurological morphology of the sciatic nerve fibers. In conclusion, SA mitigated experimental DPN, and this might be due to its ability to suppress hyperglycemic-hyperlipidemic effects, counteract the overactivation of inflammatory molecules, increase miR-146a expression, modulate oxidative dysregulation, and reduce cell apoptosis.
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Affiliation(s)
- Nema A. Mohamed
- Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Naeimah M. Shouran
- Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt
- Department of Zoology, Faculty of Science, Bani Waleed University, Bani Waleed, Libya
| | - Amina E. Essawy
- Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Ashraf M. Abdel-Moneim
- Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt
- Department of Biological Sciences, Faculty of Science, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Sherine Abdel Salam
- Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt
- Department of Biological Sciences, Faculty of Science, King Faisal University, Al-Ahsa, Saudi Arabia
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5
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Oliyaei N, Zekri S, Iraji A, Oliyaei A, Tanideh R, Mussin NM, Tamadon A, Tanideh N. Health benefits of algae and marine-derived bioactive metabolites for modulating ulcerative colitis symptoms. J Funct Foods 2025; 125:106690. [DOI: 10.1016/j.jff.2025.106690] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2025] Open
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Liu JS, Li YK, Li J, Li Y, Liu ZT, Zhou ZX, Li YG, Wang R. Ascorbate peroxidase catalyses synthesis of protocatechualdehyde from p-hydroxybenzaldehyde in Lycoris aurea. Gene 2024; 927:148697. [PMID: 38880186 DOI: 10.1016/j.gene.2024.148697] [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: 02/17/2024] [Revised: 05/10/2024] [Accepted: 06/13/2024] [Indexed: 06/18/2024]
Abstract
Protocatechualdehyde is a plant natural phenolic aldehyde and an active ingredient with important bioactivities in traditional Chinese medicine. Protocatechualdehyde is also a key intermediate in the synthesis of Amaryllidaceae alkaloids for supplying the C6-C1 skeleton. However, the biosynthesis of protocatechualdehyde in plants remains obscure. In this study, we measured the protocatechualdehyde contents in the root, bulb, scape and flower of the Amaryllidaceae plant Lycoris aurea (L'Hér.) Herb., and performed the correlation analysis between the protocatechualdehyde contents and the transcriptional levels of the phenolic oxidization candidate protein encoding genes. We found that a novel ascorbate peroxidase encoded by the contig_24999 in the L. aurea transcriptome database had potential role in the biosynthesis of protocatechualdehyde. The LauAPX_24999 gene was then cloned from the cDNA of the scape of L. aurea. The transient expression of LauAPX_24999 protein in Arabidopsis protoplasts demonstrated that LauAPX_24999 protein was localized in the cytoplasm, thus belonging to Class II L-ascorbate peroxidase. Subsequently, LauAPX_24999 protein was heterogenously expressed in Escherichia coli, and identified that LauAPX_24999 biosynthesized protocatechualdehyde from p-hydroxybenzaldehyde using L-ascorbic acid as the electron donor. The protein structure modelling and molecular docking indicated that p-hydroxybenzaldehyde could access to the active pocket of LauAPX_24999 protein, and reside at the δ-edge of the heme group while L-ascorbic acid binds at the γ-heme edge. To our knowledge, LauAPX_24999 is the first enzyme discovered in plants able to biosynthesize protocatechualdehyde from p-hydroxybenzaldehyde, and offers a competent enzyme resource for the biosynthesis of Amaryllidaceae alkaloids via synthetic biology.
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Affiliation(s)
- Jin-Shu Liu
- Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China; Engineering College, Qufu Normal University, Rizhao 276826, China.
| | - Yi-Kui Li
- Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
| | - Jie Li
- Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
| | - Yang Li
- Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
| | - Zheng-Tai Liu
- Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
| | - Zheng-Xiong Zhou
- Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China; The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
| | - Yu-Gang Li
- Engineering College, Qufu Normal University, Rizhao 276826, China.
| | - Ren Wang
- Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China; Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Nanjing 210014, China.
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7
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Zhang C, Jiang D, Shi H, Zhang C, Yang F, Qi Q, Xu R. Protective effect of fructooligosaccharide against oxidative stress and apoptosis induced by Aeromonas hydrophila in Megalobrama amblycephala. BMC Genomics 2024; 25:975. [PMID: 39415104 PMCID: PMC11484227 DOI: 10.1186/s12864-024-10881-3] [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: 08/21/2024] [Accepted: 10/08/2024] [Indexed: 10/18/2024] Open
Abstract
This research aimed to investigate the effects of dietary fructooligosaccharides (FOS) on attenuating the Aeromonas hydrophila (A. hydrophila)-induced oxidative stress and apoptosis in blunt snout bream Megalobrama amblycephala. Fish were divided into three groups as follows: C1 (Control), T1 (A. hydrophila), and T2 (A. hydrophila + 4 g/kg FOS). The results showed that the activities of antioxidant enzymes increased, the liver morphology had disorderly arrangement, and extensive cell necrosis occurred because of A. hydrophila-infection. While the dietary FOS improved the above-mentioned liver damage. Additionaly, FOS elevated mRNA levels of pro-apoptotic molecules, including caspase-8 and 9, and down-regulated mRNA levels of the anti-apoptotic molecule Bcl-2, which is triggered by A. hydrophila-infection. The transcriptome analysis showed that the oxidative stress-related DEGs pathways were activated in intestine of blunt snout bream by A. hydrophila-infection. The FOS-added group led to the enrichment of more pathways to health. Further WGCNA co-expression network analysis showed that the screened single genes were clustered into 49 modules. The two modules with the highest association to the five traits (10 hub genes) were chosen to build the network by combining the physiological and biochemical characteristic. In summary, this research offers a foundation for the exploring of A. hydrophila-restoration genes in dietary FOS, and also lays a theoretical foundation for aquaculture in the future.
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Affiliation(s)
- Chunnuan Zhang
- College of Animal Science and Technology, Henan University of Scientific and Technology, Luoyang, 471003, People's Republic of China.
| | - Dongxue Jiang
- College of Animal Science and Technology, Henan University of Scientific and Technology, Luoyang, 471003, People's Republic of China
| | - Huajuan Shi
- College of Animal Science and Technology, Henan University of Scientific and Technology, Luoyang, 471003, People's Republic of China
| | - Cheng Zhang
- College of Animal Science and Technology, Henan University of Scientific and Technology, Luoyang, 471003, People's Republic of China
| | - Feng Yang
- College of Animal Science and Technology, Henan University of Scientific and Technology, Luoyang, 471003, People's Republic of China
| | - Qian Qi
- College of Animal Science and Technology, Henan University of Scientific and Technology, Luoyang, 471003, People's Republic of China
| | - Ruiyi Xu
- College of Animal Science and Technology, Henan University of Scientific and Technology, Luoyang, 471003, People's Republic of China
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8
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Wang J, Zhang Z, Dai T, Zhang Z, Zhang Q, Yao J, Wang L, He N, Li S. The therapeutic effect and possible mechanisms of alginate oligosaccharide on metabolic syndrome by regulating gut microbiota. Food Funct 2024; 15:9632-9661. [PMID: 39239698 DOI: 10.1039/d4fo02802c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/07/2024]
Abstract
Metabolic syndrome (MetS) is a disease condition incorporating the abnormal accumulation of various metabolic components, including overweight or abdominal obesity, insulin resistance and abnormal glucose tolerance, hypertension, atherosclerosis, or dyslipidemia. It has been proved that the gut microbiota and microbial-derived products play an important role in regulating lipid metabolism and thus the onset and development of MetS. Previous studies have demonstrated that oligosaccharides with prebiotic effects, such as chitosan oligosaccharides, can regulate the structure of the microbial community and its derived products to control weight and reduce MetS associated with obesity. Alginate oligosaccharides (AOS), natural products extracted from degraded alginate salts with high solubility and extensive biological activity, have also been found to modulate gut microbiota. This review aims to summarize experimental evidence on the positive effects of AOS on different types of MetS while providing insights into mechanisms through which AOS regulates gut microbiota for preventing and treating MetS.
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Affiliation(s)
- Jingyi Wang
- School of Basic Medicine, Qingdao Medical College, Qingdao, University, Qingdao 266071, China.
- Department of Obstetrics and Gynecology, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, 266000, China
| | - Zixuan Zhang
- School of Basic Medicine, Qingdao Medical College, Qingdao, University, Qingdao 266071, China.
| | - Tong Dai
- School of Basic Medicine, Qingdao Medical College, Qingdao, University, Qingdao 266071, China.
| | - Ziheng Zhang
- School of Basic Medicine, Qingdao Medical College, Qingdao, University, Qingdao 266071, China.
| | - Qingfeng Zhang
- School of Basic Medicine, Qingdao Medical College, Qingdao, University, Qingdao 266071, China.
| | - Jingtong Yao
- School of Basic Medicine, Qingdao Medical College, Qingdao, University, Qingdao 266071, China.
| | - Lijing Wang
- School of Basic Medicine, Qingdao Medical College, Qingdao, University, Qingdao 266071, China.
- Department of Obstetrics and Gynecology, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, 266000, China
- Department of Obstetrics, Qingdao Municipal Hospital, Qingdao, 266000, China
| | - Ningning He
- School of Basic Medicine, Qingdao Medical College, Qingdao, University, Qingdao 266071, China.
| | - Shangyong Li
- School of Basic Medicine, Qingdao Medical College, Qingdao, University, Qingdao 266071, China.
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9
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Tian Y, Liu YF, Wang YY, Li YZ, Ding WY, Zhang C. Molecular mechanisms of PTEN in atherosclerosis: A comprehensive review. Eur J Pharmacol 2024; 979:176857. [PMID: 39094923 DOI: 10.1016/j.ejphar.2024.176857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Revised: 07/17/2024] [Accepted: 07/24/2024] [Indexed: 08/04/2024]
Abstract
Atherosclerosis is a chronic inflammatory disease of the arterial wall caused by an imbalance of lipid metabolism and a maladaptive inflammatory response. A variety of harmful cellular changes associated with atherosclerosis include endothelial dysfunction, the migration of circulating inflammatory cells to the arterial wall, the production of proinflammatory cytokines, lipid buildup in the intima, local inflammatory responses in blood vessels, atherosclerosis-associated apoptosis, and autophagy. PTEN inhibits the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT)/mammalian target of rapamycin (mTOR) pathway through its lipid phosphatase activity. Previous studies have shown that PTEN is closely related to atherosclerosis. This article reviews the role of PTEN in atherosclerosis from the perspectives of autophagy, apoptosis, inflammation, proliferation, and angiogenesis.
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Affiliation(s)
- Yuan Tian
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan province, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China
| | - Yi-Fan Liu
- Research Laboratory of Translational Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China
| | - Yan-Yue Wang
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan province, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China
| | - Yong-Zhen Li
- Department of Pathology, The First People's Hospital of Zigong, Zigong, China, 643099, People's Republic of China
| | - Wen-Yan Ding
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan province, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China
| | - Chi Zhang
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan province, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China.
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Feng WJ, Mou J, Liao PP, Zhou J, Zhang NN, Hu T, Wang S, Zhang SY, Mao YJ. Alginate oligosaccharides exert protective effects on hydrogen peroxide-induced senescence in H9C2 cardiomyocytes by regulating the redox state of cells. Food Sci Biotechnol 2024; 33:2835-2844. [PMID: 39184993 PMCID: PMC11339193 DOI: 10.1007/s10068-024-01534-y] [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: 06/16/2023] [Revised: 01/03/2024] [Accepted: 01/23/2024] [Indexed: 08/27/2024] Open
Abstract
Aging is a known independent risk factor for several cardiovascular diseases. Here, we evaluated potential effects and possible mechanisms through which alginate oligosaccharides (AOS) affect hydrogen peroxide (H2O2)-induced senescence in H9C2 cardiomyocytes. A series of AOS molecules, including oligoM, oligoG, M-5, and G-5, were investigated. AOS significantly decreased SA-β-gal and DAPI-stained positive cells, downregulated p53 and p21 (aging-related markers) expression, and eventually protected H9C2 cells from H2O2-induced senescence. AOS decreased reactive oxygen species and malondialdehyde production, recovered mitochondrial function, and alleviated the oxidative stress state by regulating PGC-1α and NADPH oxidase subunit expression. Furthermore, AOS treatment restored the expression of antioxidant enzymes in senescent H9C2 cells. Thus, our results show in vitro evidence that AOS alleviate senescence in H9C2 cells by regulating the redox state; thus, AOS may be an effective therapeutic agent that could protect against cardiomyocyte senescence.
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Affiliation(s)
- Wen-jing Feng
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong China
- Department of Epidemiology and Health Statistics, The School of Public Health of Qingdao University, Qingdao, 266021 Shandong China
| | - Jie Mou
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong China
| | - Ping-ping Liao
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong China
| | - Jing Zhou
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong China
| | - Nan-nan Zhang
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong China
| | - Ting Hu
- Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003 China
- Marine Biomedical Research Institute of Qingdao, Qingdao, 266073 China
| | - Shan Wang
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong China
| | - Shi-yuan Zhang
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong China
| | - Yong-jun Mao
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong China
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11
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Acevedo S, Covarrubias AA, Haeger P, Pancetti F, Tala F, de la Fuente-Ortega E. Alginate Oligosaccharides Protect Gastric Epithelial Cells against Oxidative Stress Damage through Induction of the Nrf2 Pathway. Antioxidants (Basel) 2024; 13:618. [PMID: 38790723 PMCID: PMC11117588 DOI: 10.3390/antiox13050618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 05/01/2024] [Accepted: 05/09/2024] [Indexed: 05/26/2024] Open
Abstract
Gastric diseases represent a significant global public health challenge, characterized by molecular dysregulation in redox homeostasis and heightened oxidative stress. Although prior preclinical studies have demonstrated the cytoprotective antioxidant effects of alginate oligosaccharides (AOSs) through the Nrf2 pathway, whether such mechanisms apply to gastric diseases remains unclear. In this study, we used the GES-1 gastric cell line exposed to hydrogen peroxide (H2O2) as a damage model to investigate the impact of AOS on cell viability and its associated mechanisms. Our results revealed that pre-incubation with AOS for either 4 h or 24 h significantly improved the viability of GES-1 cells exposed to H2O2. In addition, AOS reduced the intracellular ROS levels, activating the Nrf2 signaling pathway, with increased Nrf2 protein and mRNA expression and a significant upregulation of the target genes HO-1 and NQO1. The activation of Nrf2 was correlated with decreased Keap1 protein expression and an increased level of the autophagy protein p62/SQSTM1, suggesting the activation of Nrf2 through a noncanonical pathway. This study suggests that AOS is a potential treatment for protecting gastric epithelial cells from oxidative stress by activating the p62/SQSTM1-Keap1-Nrf2 axis and laying the foundation for future investigations about its specific therapeutic mechanisms.
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Affiliation(s)
- Samantha Acevedo
- Laboratorio de Estrés Celular y Enfermedades Crónicas no Transmisibles, Universidad Católica del Norte, Coquimbo 1781421, Chile;
| | - Alejandra A. Covarrubias
- Laboratorio de Neurotoxicología Ambiental, Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica del Norte, Coquimbo 1781421, Chile
- Facultad de Ciencias Agropecuarias, Universidad del Alba, La Serena 1700000, Chile
| | - Paola Haeger
- Laboratorio de Neurobiología de la Conducta, Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica del Norte, Coquimbo 1781421, Chile;
- Millennium Nucleus of Neuroepigenetics and Plasticity (EpiNeuro), Santiago 8370186, Chile
- Núcleo de Investigación en Prevención y Tratamiento de Enfermedades Crónicas no Transmisibles (NiPTEC), Universidad Católica del Norte, Coquimbo 1781421, Chile;
| | - Floria Pancetti
- Laboratorio de Neurotoxicología Ambiental, Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica del Norte, Coquimbo 1781421, Chile
- Núcleo de Investigación en Prevención y Tratamiento de Enfermedades Crónicas no Transmisibles (NiPTEC), Universidad Católica del Norte, Coquimbo 1781421, Chile;
- Centro de Investigación y Desarrollo Tecnológico en Algas y Otros Recursos Biológicos (CIDTA), Facultad de Ciencias del Mar, Universidad Católica del Norte, Coquimbo 1781421, Chile
| | - Fadia Tala
- Núcleo de Investigación en Prevención y Tratamiento de Enfermedades Crónicas no Transmisibles (NiPTEC), Universidad Católica del Norte, Coquimbo 1781421, Chile;
- Centro de Investigación y Desarrollo Tecnológico en Algas y Otros Recursos Biológicos (CIDTA), Facultad de Ciencias del Mar, Universidad Católica del Norte, Coquimbo 1781421, Chile
- Departamento de Biología Marina, Facultad de Ciencias del Mar, Universidad Católica del Norte, Coquimbo 1781421, Chile
- Instituto Milenio en Socio-Ecología Costera, SECOS, Santiago 7550000, Chile
| | - Erwin de la Fuente-Ortega
- Laboratorio de Estrés Celular y Enfermedades Crónicas no Transmisibles, Universidad Católica del Norte, Coquimbo 1781421, Chile;
- Núcleo de Investigación en Prevención y Tratamiento de Enfermedades Crónicas no Transmisibles (NiPTEC), Universidad Católica del Norte, Coquimbo 1781421, Chile;
- Centro de Investigación y Desarrollo Tecnológico en Algas y Otros Recursos Biológicos (CIDTA), Facultad de Ciencias del Mar, Universidad Católica del Norte, Coquimbo 1781421, Chile
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Moradi M, Hashemian MA, Faramarzi A, Goodarzi N, Hashemian AH, Cheraghi H, Jalili C. Therapeutic effect of sodium alginate on bleomycin, etoposide and cisplatin (BEP)-induced reproductive toxicity by inhibiting nitro-oxidative stress, inflammation and apoptosis. Sci Rep 2024; 14:1565. [PMID: 38238398 PMCID: PMC10796429 DOI: 10.1038/s41598-024-52010-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 01/12/2024] [Indexed: 01/22/2024] Open
Abstract
Impaired spermatogenesis and male infertility are common consequences of chemotherapy drugs used in patients with testicular cancer. The present study investigated the effects of sodium alginate (NaAL) on testicular toxicity caused by bleomycin, etoposide, and cisplatin (BEP). Rats in group 1 received normal saline, while groups 2 and 3 were treated with 25 and 50 mg/kg of NaAL, respectively. Group 4 was treated with a 21-day cycle of BEP (0.5 mg/kg bleomycin, 5 mg/kg etoposide, and 1 mg/kg cisplatin), and groups 5 and 6 received BEP regimen plus 25 and 50 mg/kg of NaAL, respectively. Then, sperm parameters, testosterone levels, testicular histopathology and stereological parameters, testicular levels of malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC), and the expression of apoptosis-associated genes including Bcl2, Bax, Caspase3, p53, and TNF-α were evaluated. Our findings revealed that NaAL improved sperm parameters, testosterone levels, histopathology, and stereology parameters in BEP-administrated rats. NaAL also improved testis antioxidant status by enhancing TAC and ameliorating MDA and NO. Further, modifications to the expression of Bcl2, Bax, Caspase3, p53, and TNF-α suggested that NaAL alleviated BEP-induced apoptosis and inflammation. Collectively, NaAL protects rats' testes against BEP-evoked toxicity damage through the modulation of nitro-oxidative stress, apoptosis, and inflammation.
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Affiliation(s)
- Mojtaba Moradi
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | | | - Azita Faramarzi
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Department of Anatomical Sciences, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - Nader Goodarzi
- Department of Basic and Pathobiological Sciences, Faculty of Veterinary Medicine, Razi Universtiy, Kermanshah, Iran.
| | - Amir Hossein Hashemian
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Department of Biostatistics, School of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Hadi Cheraghi
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran
| | - Cyrus Jalili
- Department of Anatomical Sciences, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Zhang E, Shang C, Ma M, Zhang X, Liu Y, Song S, Li X. Polyguluronic acid alleviates doxorubicin-induced cardiotoxicity by suppressing Peli1-NLRP3 inflammasome-mediated pyroptosis. Carbohydr Polym 2023; 321:121334. [PMID: 37739547 DOI: 10.1016/j.carbpol.2023.121334] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 08/22/2023] [Accepted: 08/24/2023] [Indexed: 09/24/2023]
Abstract
Polyguluronic acid (PG), a polysaccharide from alginate, possesses excellent bioactivities. We prepared high-purity PG with 10.41 kDa molecular weight (Mw) and a 59 average degree of polymerization (DP) by acid hydrolysis, three pH grades, Q-Sepharose column elution, and Sephadex G-25 column desalination. Then, we evaluated the PG protective effects on doxorubicin-induced cardiotoxicity (DIC) in vitro and in vivo. The nontoxic PG enhanced cellular viability, reduced cell pyroptosis morphology, diminished the LDH and IL-1β release, and downregulated expressions of ASC oligomerization, NLRP3, cl-CASP1, and GSDMD, by which PG protected the cardiomyocytes from NLRP3 inflammasome-mediated pyroptosis in doxorubicin-stimulated HL-1 cells and C57BL/6J mice. The probable underlying mechanism may be that PG downregulated doxorubicin -induced Peli1, the deficiency of which could inhibit doxorubicin-induced NLRP3 inflammasome-mediated pyroptosis. These results suggested that polysaccharide PG from alginate could prevent DIC and may be a potential therapeutic agent or bioactive material for preventing DIC.
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Affiliation(s)
- E Zhang
- Marine College, Shandong University, Weihai, Shandong 264209, China.
| | - Chuangeng Shang
- Marine College, Shandong University, Weihai, Shandong 264209, China.
| | - Mingtao Ma
- Marine College, Shandong University, Weihai, Shandong 264209, China.
| | - Xuanfeng Zhang
- Marine College, Shandong University, Weihai, Shandong 264209, China.
| | - Yu Liu
- Marine College, Shandong University, Weihai, Shandong 264209, China.
| | - Shuliang Song
- Marine College, Shandong University, Weihai, Shandong 264209, China.
| | - Xia Li
- Marine College, Shandong University, Weihai, Shandong 264209, China; School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
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Luo X. Nanobiotechnology-based strategies in alleviation of chemotherapy-mediated cardiotoxicity. ENVIRONMENTAL RESEARCH 2023; 238:116989. [PMID: 37633635 DOI: 10.1016/j.envres.2023.116989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/19/2023] [Accepted: 08/23/2023] [Indexed: 08/28/2023]
Abstract
The cardiovascular diseases have been among the most common malignancies and the first leading cause of death, even higher than cancer. The cardiovascular diseases can be developed as a result of cardiac dysfunction and damages to heart tissue. Exposure to toxic agents and chemicals that induce cardiac dysfunction has been of interest in recent years. The chemotherapy drugs are commonly used for cancer therapy and in these patients, cardiovascular diseases have been widely observed that is due to negative impact of chemotherapy drugs on the heart. These drugs increase oxidative damage and inflammation, and mediate apoptosis and cardiac dysfunction. Hence, nanotechnological approaches have been emerged as new strategies in attenuation of chemotherapy-mediated cardiotoxicity. The first advantage of nanoparticles can be explored in targeted and selective delivery of drugs to reduce their accumulation in heart tissue. Nanostructures can deliver bioactive and therapeutic compounds in reducing cardiotoxicity and alleviation toxic impacts of chemotherapy drugs. The functionalization of nanostructures increases their selectivity against tumor cells and reduces accumulation of drugs in heart tissue. The bioplatforms such as chitosan and alginate nanostructures can also deliver chemotherapy drugs and reduce their cardiotoxicity. The function of nanostructures is versatile in reduction of cardiotoxicity by chemotherapy drugs and new kind of platforms is hydrogels that can mediate sustained release of drug to reduce its toxic impacts on heart tissue. The various kinds of nanoplatforms have been developed for alleviation of cardiotoxicity and their future clinical application depends on their biocompatibility. High concentration level of chitosan nanoparticles can stimulate cardiotoxicity. Therefore, if nanotechnology is going to be deployed for drug delivery and reducing cardiotoxicity, the first pre-requirement is to lack toxicity on normal cells and have high biocompatibility.
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Affiliation(s)
- Xuanming Luo
- Department of General Surgery, Zhongshan Hospital, Fudan University, China; Department of General Surgery, Shanghai Xuhui Central Hospital, Fudan University, China; Biliary Tract Disease Center of Zhongshan Hospital, Fudan University, China; Cancer Center, Zhongshan Hospital, Fudan University, China; Biliary Tract Disease Institute, Fudan University, China; Shanghai Engineering Research Center of Biliary Tract Minimal Invasive Surgery and Materials, China.
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15
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Dabravolski SA, Sukhorukov VN, Melnichenko AA, Khotina VA, Orekhov AN. Oligosaccharides as Potential Therapeutics against Atherosclerosis. Molecules 2023; 28:5452. [PMID: 37513323 PMCID: PMC10386248 DOI: 10.3390/molecules28145452] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/13/2023] [Accepted: 07/14/2023] [Indexed: 07/30/2023] Open
Abstract
Atherosclerosis is the major cause of cardiovascular-disease-related death worldwide, resulting from the subendothelial accumulation of lipoprotein-derived cholesterol, ultimately leading to chronic inflammation and the formation of clinically significant atherosclerotic plaques. Oligosaccharides have been widely used in biomedical research and therapy, including tissue engineering, wound healing, and drug delivery. Moreover, oligosaccharides have been consumed by humans for centuries, and are cheap, and available in large amounts. Given the constantly increasing number of obesity, diabetes, and hyperlipidaemia cases, there is an urgent need for novel therapeutics that can economically and effectively slow the progression of atherosclerosis. In this review, we address the current state of knowledge in oligosaccharides research, and provide an update of the recent in vitro and in vivo experiments that precede clinical studies. The application of oligosaccharides could help to eliminate the residual risk after the application of other cholesterol-lowering medicines, and provide new therapeutic opportunities to reduce the associated burden of premature deaths because of atherosclerosis.
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Affiliation(s)
- Siarhei A Dabravolski
- Department of Biotechnology Engineering, Braude Academic College of Engineering, Snunit 51, P.O. Box 78, Karmiel 2161002, Israel
| | - Vasily N Sukhorukov
- Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Street, 125315 Moscow, Russia
| | - Alexandra A Melnichenko
- Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Street, 125315 Moscow, Russia
| | - Victoria A Khotina
- Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Street, 125315 Moscow, Russia
| | - Alexander N Orekhov
- Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Street, 125315 Moscow, Russia
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16
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Jin QR, Mao JW, Zhu F. Effects of Hizikia fusiforme polysaccharides on innate immunity and disease resistance of the mud crab Scylla paramamosain. FISH & SHELLFISH IMMUNOLOGY 2023; 135:108655. [PMID: 36868537 DOI: 10.1016/j.fsi.2023.108655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 02/26/2023] [Accepted: 02/28/2023] [Indexed: 06/18/2023]
Abstract
In this study, we extracted the polysaccharides from Hizikia fusiforme (HFPs) and evaluated their effects on the immune response of the mud crab Scylla paramamosain. Compositional analysis revealed that HFPs were composed mainly of mannuronic acid (49.05%) and fucose (22.29%) as sulfated polysaccharides, and the sugar chain structure was β-type. These results indicated that HFPs have potential antioxidant and immunostimulation activity in vivo or in vitro assays. Through this research, we found that HFPs inhibited viral replication in white spot syndrome virus (WSSV)-infected crabs and promoted phagocytosis of Vibrio alginolyticus by hemocytes. Quantitative PCR results showed that HFPs up-regulated the expression levels of astakine, crustin, myosin, MCM7, STAT, TLR, JAK, CAP, and p53 in crab hemocytes. HFPs also promoted the activities of superoxide dismutase and acid phosphatase and the hemolymph antioxidant activities of crabs. HFPs maintained peroxidase activity after WSSV challenge, thereby providing protection against oxidative damage caused by the virus. HFPs also promoted apoptosis of hemocytes after WSSV infection. In addition, HFPs significantly enhanced the survival rate of WSSV-infected crabs. All results confirmed that HFPs improved the innate immunity of S. paramamosain by enhancing the expression of antimicrobial peptides, antioxidant enzyme activity, phagocytosis, and apoptosis. Therefore, HFPs have potential for use as therapeutic or preventive agents to regulate the innate immunity of mud crabs and protect them against microbial infection.
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Affiliation(s)
- Qing-Ri Jin
- School of Pharmacy, Hangzhou Medical College, Hangzhou, 311399, China
| | - Jing-Wei Mao
- Key Laboratory of Applied Technology of Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A＆F University, Hangzhou, 311300, China
| | - Fei Zhu
- Key Laboratory of Applied Technology of Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A＆F University, Hangzhou, 311300, China.
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Abstract
Fecal microbiota transplantation (FMT) is an effective means of modulating gut microbiota for the treatment of many diseases, including Clostridioides difficile infections. The gut-spleen axis has been established, and this is involved in the development and function of the spleen. However, it is not understood whether gut microbiota can be used to improve spleen function, especially in spleens disrupted by a disease or an anti-cancer treatment. In the current investigation, we established that alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) can rescue anticancer drug busulfan-disrupted spleen vasculature and spleen function. A10-FMT improved the gene and/or protein expression of genes involved in vasculature development, increased the cell proliferation rate, enhanced the endothelial progenitor cell capability, and elevated the expression of the cell junction molecules to increase the vascularization of the spleen. This investigation found for the first time that the reestablishment of spleen vascularization restored spleen function by improving spleen immune cells and iron metabolism. These findings may be used as a strategy to minimize the side effects of anti-cancer drugs or to improve spleen vasculature-related diseases. IMPORTANCE Alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) can rescue busulfan disrupted spleen vasculature. A10-FMT improved the cell proliferation rate, endothelial progenitor cell capability, and cell junction molecules to increase vasculature formation in the spleen. This reestablishment restored spleen function by improving spleen immune cells and iron metabolism. These findings are useful for the treatment of spleen vasculature-related diseases.
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18
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Effects of Alginate Oligosaccharide on Testosterone-Induced Benign Prostatic Hyperplasia in Orchiectomized Rats. Nutrients 2023; 15:nu15030682. [PMID: 36771389 PMCID: PMC9920801 DOI: 10.3390/nu15030682] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/25/2023] [Accepted: 01/27/2023] [Indexed: 01/31/2023] Open
Abstract
Benign prostatic hyperplasia (BPH) is an age-related disease of the urinary system that affects elderly men. Current treatments for BPH are associated with several adverse effects, thus highlighting the need for alternative agents. Alginate oligosaccharide (AOS), a water-soluble functional oligomer derived from brown algae, inhibits prostate cancer cell proliferation. However, the effects of AOS on BPH and the underlying molecular mechanisms remain unclear. Therefore, here, we aimed to investigate the therapeutic potential of AOS in BPH by using human benign prostatic epithelial cells (BPH-1) and a rat model of testosterone-induced BPH. Treatment with AOS inhibited in vitro and in vivo proliferation of prostatic epithelial cells and the testosterone-induced expression of androgen receptor (AR) and androgen-associated genes, such as those encoding 5α-reductase type 2 and prostate-specific antigen. Oral administration of AOS remarkably reduced the serum levels of dihydrotestosterone (DHT) and testosterone as well as the expression of proliferating cell nuclear antigen, inflammatory cytokines, and enzymes, which showed increased levels in prostatic tissues of rats with testosterone-induced BPH. Taken together, these data demonstrate that AOS suppresses testosterone-induced BPH in rats by downregulating AR and the expression of androgen-associated genes, supporting the hypothesis that AOS might be of potential use for the treatment of BPH.
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19
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Wu A, Gao Y, Kan R, Ren P, Xue C, Kong B, Tang Q. Alginate Oligosaccharides Prevent Dextran-Sulfate-Sodium-Induced Ulcerative Colitis via Enhancing Intestinal Barrier Function and Modulating Gut Microbiota. Foods 2023; 12:foods12010220. [PMID: 36613442 PMCID: PMC9818813 DOI: 10.3390/foods12010220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/22/2022] [Accepted: 12/27/2022] [Indexed: 01/05/2023] Open
Abstract
Alginate oligosaccharides are degradation products of alginate and have attracted increasing attention due to their versatile biological functions. In the present study, C57BL/6 mice were used to assess the ameliorative effects and mechanisms of guluronate oligosaccharides (GAOS), mannuronic oligosaccharides (MAOS), and heterozygous alginate oligosaccharides (HAOS), which are the three alginate oligosaccharides of dextran sulfate sodium (DSS)-induced ulcerative colitis. The study showed that alginate oligosaccharides alleviated pathological histological damage by slowing down weight loss, inhibiting colonic length shortening, and reducing disease activity index (DAI) and histopathological scores. Alginate oligosaccharides modulated the colonic inflammatory response by reducing colonic MPO levels and downregulating the expression of IL-6 and IL-1β. Alginate oligosaccharides reduced intestinal permeability and reversed intestinal barrier damage by increasing the number of goblet cells, decreasing LPS levels, downregulating Bax protein levels, upregulating Bcl-2 protein levels, and enhancing the expression of the E-cadherin. Furthermore, alginate oligosaccharides modulated the composition of the gut microbiota and restored the production of short-chain fatty acids (SCFAs), especially acetate and butyrate. In conclusion, our study provides a scientific basis for the role of alginate oligosaccharides in relieving ulcerative colitis.
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Affiliation(s)
- Axue Wu
- College of Food Science and Engineering, Ocean University of China, Qingdao 266100, China
| | - Yuan Gao
- College of Food Science and Engineering, Ocean University of China, Qingdao 266100, China
| | - Ruotong Kan
- College of Food Science and Engineering, Ocean University of China, Qingdao 266100, China
| | - Pengfei Ren
- College of Food Science and Engineering, Ocean University of China, Qingdao 266100, China
| | - Changhu Xue
- College of Food Science and Engineering, Ocean University of China, Qingdao 266100, China
- Qingdao National Laboratory for Marine Science and Technology, Qingdao 266100, China
| | - Biao Kong
- Department of Chemistry, Shanghai Key Lab of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200438, China
| | - Qingjuan Tang
- College of Food Science and Engineering, Ocean University of China, Qingdao 266100, China
- Correspondence: ; Tel.: +86-13912383919
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Li F, Tang Y, Wei L, Yang M, Lu Z, Shi F, Zhan F, Li Y, Liao W, Lin L, Qin Z. Alginate oligosaccharide modulates immune response, fat metabolism, and the gut bacterial community in grass carp (Ctenopharyngodon idellus). FISH & SHELLFISH IMMUNOLOGY 2022; 130:103-113. [PMID: 36044935 DOI: 10.1016/j.fsi.2022.08.067] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/23/2022] [Accepted: 08/23/2022] [Indexed: 06/15/2023]
Abstract
Alginate oligosaccharide (AOS) is widely used in agriculture because of its many excellent biological properties. However, the possible beneficial effects of AOS and their underlying mechanisms are currently not well known in grass carp (Ctenopharyngodon idellus). Here, grass carp were fed diets supplemented with 5, 10, or 20 g/kg AOS for six weeks. HE and PAS staining showed that the diets of AOS significantly increased the number of goblet cells in the intestinal. According to transcriptome and quantitative real-time PCR (qRT-PCR) data, AOS-supplemented diets activated the expression of fat metabolism-related pathways and genes. The 16S rRNA sequencing results showed that supplementation with AOS affected the distribution and abundance of the gut bacterial assembly. qRT-PCR and activity assays revealed that the AOS diets significantly increased the antioxidant resistance in gut of grass carp, and down-regulated the expression of inflammatory and up-regulated anti-inflammatory cytokines. Finally, the Aeromonas hydrophila infection assay suggested that the mortality in the groups fed dietary AOS was slightly lower than that in the control. Therefore, supplementing the diet of grass carp with an appropriate amount of AOS can improve fat metabolism and immune responses and alter the intestinal bacterial community, which may help to fight bacterial infection.
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Affiliation(s)
- Fenglin Li
- Guangdong Provincial Water Environment and Aquatic Products Security Engineering Technology Research Center, Guangzhou Key Laboratory of Aquatic Animal Diseases and Waterfowl Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong Province, 510222, China
| | - Ying Tang
- Guangdong Provincial Water Environment and Aquatic Products Security Engineering Technology Research Center, Guangzhou Key Laboratory of Aquatic Animal Diseases and Waterfowl Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong Province, 510222, China
| | - Lixiang Wei
- Guangdong Provincial Water Environment and Aquatic Products Security Engineering Technology Research Center, Guangzhou Key Laboratory of Aquatic Animal Diseases and Waterfowl Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong Province, 510222, China
| | - Minxuan Yang
- Guangdong Provincial Water Environment and Aquatic Products Security Engineering Technology Research Center, Guangzhou Key Laboratory of Aquatic Animal Diseases and Waterfowl Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong Province, 510222, China
| | - Zhijie Lu
- Guangdong Provincial Water Environment and Aquatic Products Security Engineering Technology Research Center, Guangzhou Key Laboratory of Aquatic Animal Diseases and Waterfowl Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong Province, 510222, China
| | - Fei Shi
- Guangdong Provincial Water Environment and Aquatic Products Security Engineering Technology Research Center, Guangzhou Key Laboratory of Aquatic Animal Diseases and Waterfowl Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong Province, 510222, China
| | - Fanbin Zhan
- Guangdong Provincial Water Environment and Aquatic Products Security Engineering Technology Research Center, Guangzhou Key Laboratory of Aquatic Animal Diseases and Waterfowl Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong Province, 510222, China
| | - Yanan Li
- Guangdong Provincial Water Environment and Aquatic Products Security Engineering Technology Research Center, Guangzhou Key Laboratory of Aquatic Animal Diseases and Waterfowl Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong Province, 510222, China
| | - Wenchong Liao
- South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, 510301, China
| | - Li Lin
- Guangdong Provincial Water Environment and Aquatic Products Security Engineering Technology Research Center, Guangzhou Key Laboratory of Aquatic Animal Diseases and Waterfowl Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong Province, 510222, China; Southern Marine Science and Engineering Guangdong Laboratory, Zhanjiang, 524025, China.
| | - Zhendong Qin
- Guangdong Provincial Water Environment and Aquatic Products Security Engineering Technology Research Center, Guangzhou Key Laboratory of Aquatic Animal Diseases and Waterfowl Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong Province, 510222, China.
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21
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Alginate Oligosaccharides Ameliorate DSS-Induced Colitis through Modulation of AMPK/NF-κB Pathway and Intestinal Microbiota. Nutrients 2022; 14:nu14142864. [PMID: 35889822 PMCID: PMC9321948 DOI: 10.3390/nu14142864] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 07/07/2022] [Accepted: 07/11/2022] [Indexed: 02/04/2023] Open
Abstract
Alginate oligosaccharides (AOS) are shown to have various biological activities of great value to medicine, food, and agriculture. However, little information is available about their beneficial effects and mechanisms on ulcerative colitis. In this study, AOS with a polymerization degree between 2 and 4 were found to possess anti-inflammatory effects in vitro and in vivo. AOS could decrease the levels of nitric oxide (NO), IL-1β, IL-6, and TNFα, and upregulate the levels of IL-10 in both RAW 264.7 and bone-marrow-derived macrophage (BMDM) cells under lipopolysaccharide (LPS) stimulation. Additionally, oral AOS administration could significantly prevent bodyweight loss, colonic shortening, and rectal bleeding in dextran sodium sulfate (DSS)-induced colitis mice. AOS pretreatment could also reduce disease activity index scores and histopathologic scores and downregulate proinflammatory cytokine levels. Importantly, AOS administration could reverse DSS-induced AMPK deactivation and NF-κB activation in colonic tissues, as evidenced by enhanced AMPK phosphorylation and p65 phosphorylation inhibition. AOS could also upregulate AMPK phosphorylation and inhibit NF-κB activation in vitro. Moreover, 16S rRNA gene sequencing of gut microbiota indicated that supplemental doses of AOS could affect overall gut microbiota structure to a varying extent and specifically change the abundance of some bacteria. Medium-dose AOS could be superior to low- or high-dose AOS in maintaining remission in DSS-induced colitis mice. In conclusion, AOS can play a protective role in colitis through modulation of gut microbiota and the AMPK/NF-kB pathway.
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22
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Bi D, Yang X, Lu J, Xu X. Preparation and potential applications of alginate oligosaccharides. Crit Rev Food Sci Nutr 2022; 63:10130-10147. [PMID: 35471191 DOI: 10.1080/10408398.2022.2067832] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Alginate, a linear polymer consisting of β-D-mannuronic acid (M) and α-L-guluronic acid (G) with 1,4-glycosidic linkages and comprising 40% of the dry weight of algae, possesses various applications in the food and nutraceutical industries. However, the potential applications of alginate are restricted in some fields because of its low water solubility and high solution viscosity. Alginate oligosaccharides (AOS) on the other hand, have low molecular weight which result in better water solubility. Hence, it becomes a more popular target to be researched in recent years for its use in foods and nutraceuticals. AOS can be obtained by multiple degradation methods, including enzymatic degradation, from alginate or alginate-derived poly G and poly M. AOS have unique bioactivity and can bring human health benefits, which render them potentials to be developed/incorporated into functional food. This review comprehensively covers methods of the preparation and analysis of AOS, and discussed the potential applications of AOS in foods and nutraceuticals.
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Affiliation(s)
- Decheng Bi
- Shenzhen Key Laboratory of Marine Bioresources and Ecology, and Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, PR China
- School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand
| | - Xu Yang
- School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand
| | - Jun Lu
- School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand
- School of Public Health and Interdisciplinary Studies, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand
- Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand
| | - Xu Xu
- Shenzhen Key Laboratory of Marine Bioresources and Ecology, and Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, PR China
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23
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Sulfated alginate oligosaccharide exerts antitumor activity and autophagy induction by inactivating MEK1/ERK/mTOR signaling in a KSR1-dependent manner in osteosarcoma. Oncogenesis 2022; 11:16. [PMID: 35418575 PMCID: PMC9008062 DOI: 10.1038/s41389-022-00390-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 03/12/2022] [Accepted: 03/18/2022] [Indexed: 11/08/2022] Open
Abstract
Alginate oligosaccharide (AOS) has the function to inhibit tumor progression and the sulfated modification can enhance the antitumor activity. To date, the function and mechanism of sulfated AOS (AOS-SO4) in tumors remain largely elusive. We prepared AOS by the enzymatic degradation of alginate, collected AOS-SO4 by sulfating following the canonical procedure. Using these materials, in vitro assays showed that both AOS and AOS-SO4 elicited antitumor effects in osteosarcoma cells. Sulfated modification significantly enhanced the antitumor activity. In addition, AOS-SO4 had obvious effects on cell cycle arrest, apoptosis, and autophagy induction in vitro and in vivo. Mechanistically, we observed that AOS-SO4 treatment triggered proapoptotic autophagy by inhibiting MEK1/ERK/mTOR signaling. The ERK activator reversed AOS-SO4-induced autophagy. More importantly, we found that KSR1 interacted with MEK1 and functioned as a positive regulator of MEK1 protein in osteosarcoma cells. High KSR1 expression was significantly associated with poor survival in osteosarcoma patients. Together, these results suggest that AOS-SO4 has a better antitumor effect in osteosarcoma by inhibiting MEK1/ERK/mTOR signaling, which is KSR1-dependent; thus, AOS-SO4 can be a new potential therapeutic candidate for the treatment of osteosarcoma.
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24
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Hamouda RA, Salman AS, Alharbi AA, Alhasani RH, Elshamy MM. Assessment of the Antigenotoxic Effects of Alginate and ZnO/Alginate-Nanocomposites Extracted from Brown Alga Fucus vesiculosus in Mice. Polymers (Basel) 2021; 13:polym13213839. [PMID: 34771394 PMCID: PMC8587912 DOI: 10.3390/polym13213839] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 10/29/2021] [Accepted: 11/01/2021] [Indexed: 01/01/2023] Open
Abstract
Mitomycin C (MMC) is an alkylating chemotherapy drug that could induce DNA damage and genetic alteration. It has been used as a model mutagen for in vivo and in vitro studies. The current study aimed to evaluate the protective role of Zinc oxide alginate–nanocomposites (ZnO-Alg/NCMs) against MMC–induced genotoxicity in mice. Animals were treated as follows: the control group, the groups treated with Algin (400 mg/kg b.w), the groups treated with ZnO-Alg/NCMs (400 mg/kg b.w), the group treated with MMC, and the groups treated with MMC plus Algin or ZnO-Alg/NCMs. Pre-treatment with Algin and ZnO-Alg/NCMs was repeated for one or seven days. Zinc oxide alginate-nanocomposites (ZnO-Alg/NCMs) were synthesized with the aim of incorporating the intrinsic properties of their constituents as an antigenotoxic substance. In this study, alginate was extracted from the brown marine alga Fucus vesiculosus, Zinc oxide nanoparticles were synthesized by using water extract of the same alga, and loaded in alginate to synthesize ZnO-Alg/NCMs. ZnO-NPs and ZnO-Alg/NCMs were characterized by TEM, SEM, EDX, and Zeta potential. The obtained results confirmed that by TEM and SEM, ZnO-NPs are rod shaped which modified, when loaded in alginate matrix, into spherical shape. The physical stability of ZnO-Alg/NCMs was reported to be higher than ZnO-NPs due to the presence of more negative charges on ZnO-Alg/NCMs. The EDX analysis indicated that the amount of zinc was higher in ZnO-NPs than ZnO-Alg/NCMs. The in vivo results showed that treatment with MMC induced genotoxic disturbances. The combined treatment with Algin and ZnO-Alg/NCMs succeeded in inducing significant protection against MMC. It could be concluded that ZnO-Algin/NCMs is a promising candidate to protect against MMC–induced genotoxicity.
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Affiliation(s)
- Ragaa A. Hamouda
- Department of Biology, College of Sciences and Arts Khulais, University of Jeddah, Jeddah 21959, Saudi Arabia; (A.S.S.); (A.A.A.)
- Microbial Biotechnology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Sadat City 32897, Egypt
- Correspondence:
| | - Asmaa S. Salman
- Department of Biology, College of Sciences and Arts Khulais, University of Jeddah, Jeddah 21959, Saudi Arabia; (A.S.S.); (A.A.A.)
- Genetic and Cytology Department, National Research Center, Cairo 12622, Egypt
| | - Asrar A. Alharbi
- Department of Biology, College of Sciences and Arts Khulais, University of Jeddah, Jeddah 21959, Saudi Arabia; (A.S.S.); (A.A.A.)
| | - Reem Hasaballah Alhasani
- Department of Biology, Faculty of Applied Science, Umm Al-Qura University, Makkah 21961, Saudi Arabia;
| | - Maha M. Elshamy
- Botany Department, Faculty of Science, Mansoura University, Mansoura 35516, Egypt;
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25
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Han ZL, Chen M, Fu XD, Yang M, Hrmova M, Zhao YH, Mou HJ. Potassium Alginate Oligosaccharides Alter Gut Microbiota, and Have Potential to Prevent the Development of Hypertension and Heart Failure in Spontaneously Hypertensive Rats. Int J Mol Sci 2021; 22:ijms22189823. [PMID: 34575987 PMCID: PMC8470992 DOI: 10.3390/ijms22189823] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 08/31/2021] [Accepted: 09/06/2021] [Indexed: 12/12/2022] Open
Abstract
Food-derived oligosaccharides show promising therapeutic potential in lowering blood pressure (BP), but the mechanism is poorly understood. Recently, the potential role of gut microbiota (GM) in hypertension has been investigated, but the specific GM signature that may participate in hypertension remains unclear. To test the potassium alginate oligosaccharides (PAO) mechanism in lowering BP and specific microbial signature changes in altering GM, we administered various dosages of PAO in 40 spontaneously hypertensive rats for a duration of six weeks. We analyzed BP, sequenced the 16S ribosomal DNA gene in the cecum content, and gathered RNA-seq data in cardiac tissues. We showed that the oral administration of PAO could significantly decrease systolic BP and mean arterial pressure. Transcriptome analyses demonstrated that the protective effects of developing heart failure were accompanied by down-regulating of the Natriuretic Peptide A gene expression and by decreasing the concentrations of angiotensin II and atrial natriuretic peptide in plasma. In comparison to the Vehicle control, PAO could increase the microbial diversity by altering the composition of GM. PAO could also decrease the ratio of Firmicutes to Bacteroidetes by decreasing the abundance of Prevotella and Phascolarctobacterium bacteria. The favorable effect of PAO may be added to the positive influence of the abundance of major metabolites produced by Gram-negative bacteria in GM. We suggest that PAO caused changes in GM, and thus, they played an important role in preventing the development of cardiovascular disease.
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Affiliation(s)
- Zhen-Lian Han
- School of Life Science, Huaiyin Normal University, 111 West Changjiang Road, Huai’an 223300, China; (Z.-L.H.); (M.H.)
- College of Food Science & Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; (M.C.); (X.-D.F.)
| | - Meng Chen
- College of Food Science & Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; (M.C.); (X.-D.F.)
| | - Xiao-Dan Fu
- College of Food Science & Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; (M.C.); (X.-D.F.)
| | - Min Yang
- Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China;
| | - Maria Hrmova
- School of Life Science, Huaiyin Normal University, 111 West Changjiang Road, Huai’an 223300, China; (Z.-L.H.); (M.H.)
| | - Yuan-Hui Zhao
- College of Food Science & Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; (M.C.); (X.-D.F.)
- Correspondence: (Y.-H.Z.); (H.-J.M.); Tel./Fax: +86-532-8203-2400 (Y.-H.Z.); +86-532-8203-2290 (H.-J.M.)
| | - Hai-Jin Mou
- College of Food Science & Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; (M.C.); (X.-D.F.)
- Correspondence: (Y.-H.Z.); (H.-J.M.); Tel./Fax: +86-532-8203-2400 (Y.-H.Z.); +86-532-8203-2290 (H.-J.M.)
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26
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Zhang C, Li M, Rauf A, Khalil AA, Shan Z, Chen C, Rengasamy KRR, Wan C. Process and applications of alginate oligosaccharides with emphasis on health beneficial perspectives. Crit Rev Food Sci Nutr 2021; 63:303-329. [PMID: 34254536 DOI: 10.1080/10408398.2021.1946008] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Alginates are linear polymers comprising 40% of the dry weight of algae possess various applications in food and biomedical industries. Alginate oligosaccharides (AOS), a degradation product of alginate, is now gaining much attention for their beneficial role in food, pharmaceutical and agricultural industries. Hence this review was aimed to compile the information on alginate and AOS (prepared from seaweeds) during 1994-2020. As per our knowledge, this is the first review on the potential use of alginate oligosaccharides in different fields. The alginate derivatives are grouped according to their applications. They are involved in the isolation process and show antimicrobial, antioxidant, anti-inflammatory, antihypertension, anticancer, and immunostimulatory properties. AOS also have significant applications in prebiotics, nutritional supplements, plant growth development and others products.
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Affiliation(s)
- Chunhua Zhang
- College of Agriculture and Forestry, Pu'er University, Pu'er, Yunnan, China
| | - Mingxi Li
- Research Center of Tea and Tea Culture, College of Agronomy, Jiangxi Agricultural University, Nanchang, Jiangxi, China
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Khyber Pakhtunkhwa (KP), Pakistan
| | - Anees Ahmed Khalil
- University Institute of Diet and Nutritional Sciences, Faculty of Diet and Nutritional Sciences, The University of Lahore, Lahore, Pakistan
| | - Zhiguo Shan
- College of Agriculture and Forestry, Pu'er University, Pu'er, Yunnan, China
| | - Chuying Chen
- Research Center of Tea and Tea Culture, College of Agronomy, Jiangxi Agricultural University, Nanchang, Jiangxi, China
| | - Kannan R R Rengasamy
- Green Biotechnologies Research Centre of Excellence, University of Limpopo, Polokwane, Sovenga, South Africa
| | - Chunpeng Wan
- Research Center of Tea and Tea Culture, College of Agronomy, Jiangxi Agricultural University, Nanchang, Jiangxi, China
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27
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Wang M, Chen L, Zhang Z. Potential applications of alginate oligosaccharides for biomedicine - A mini review. Carbohydr Polym 2021; 271:118408. [PMID: 34364551 DOI: 10.1016/j.carbpol.2021.118408] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 06/23/2021] [Accepted: 07/03/2021] [Indexed: 01/02/2023]
Abstract
Extensive research on marine algae, especially on their health-promoting properties, has been conducted. Various ingredients with potential biomedical applications have been discovered and extracted from marine algae. Alginate oligosaccharides are low molecular weight alginate polysaccharides present in cell walls of brown algae. They exhibit various health benefits such as anti-inflammatory, anti-microbial, anti-oxidant, anti-tumor and immunomodulation. Their low-toxicity, non-immunogenicity, and biodegradability make them an excellent material in biomedicine. Alginate oligosaccharides can be chemically or biochemically modified to enhance their biological activity and potential in pharmaceutical applications. This paper provides a brief overview on alginate oligosaccharides characteristics, modification patterns and highlights their vital health promoting properties.
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Affiliation(s)
- Mingpeng Wang
- College of Life Science, Qufu Normal University, Qufu 273100, China
| | - Lei Chen
- College of Life Science, Qufu Normal University, Qufu 273100, China.
| | - Zhaojie Zhang
- Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming, USA
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28
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Feng W, Liu J, Wang S, Hu Y, Pan H, Hu T, Guan H, Zhang D, Mao Y. Alginate oligosaccharide alleviates D-galactose-induced cardiac ageing via regulating myocardial mitochondria function and integrity in mice. J Cell Mol Med 2021; 25:7157-7168. [PMID: 34227740 PMCID: PMC8335675 DOI: 10.1111/jcmm.16746] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 05/23/2021] [Accepted: 05/25/2021] [Indexed: 12/21/2022] Open
Abstract
Ageing is a crucial risk factor for the development of age‐related cardiovascular diseases. Therefore, the molecular mechanisms of ageing and novel anti‐ageing interventions need to be deeply studied. Alginate oligosaccharide (AOS) possesses high pharmacological activities and beneficial effects. Our study was undertaken to investigate whether AOS could be used as an anti‐ageing drug to alleviate cardiac ageing. D‐galactose (D‐gal)‐induced C57BL/6J ageing mice were established by subcutaneous injection of D‐gal (200 mg·kg‐1·d‐1) for 8 weeks. AOS (50, 100 and 150 mg·kg‐1·d‐1) were administrated intragastrically for the last 4 weeks. As a result, AOS prevented cardiac dysfunction in D‐gal‐induced ageing mice, including partially preserved ejection fraction (EF%) and fractional shortening (FS%). AOS inhibited D‐gal‐induced up‐regulation of natriuretic peptides A (ANP), brain natriuretic peptide (BNP) and ageing markers p53 and p21 in a dose‐dependent manner. To further explore the potential mechanisms contributing to the anti‐ageing protective effect of AOS, the age‐related mitochondrial compromise was analysed. Our data indicated that AOS alleviated D‐gal‐induced cardiac ageing by improving mitochondrial biogenesis, maintaining the mitochondrial integrity and enhancing the efficient removal of impaired mitochondria. AOS also decreased the ROS production and oxidative stress status, which, in turn, further inhibiting cardiac mitochondria from being destroyed. Together, these results demonstrate that AOS may be an effective therapeutic agent to alleviate cardiac ageing.
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Affiliation(s)
- Wenjing Feng
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.,Department of Epidemiology and Health Statistics, The School of Public Health of Qingdao University, Qingdao, China
| | - Jianya Liu
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shan Wang
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yi Hu
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Hui Pan
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ting Hu
- Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.,Marine Biomedical Research Institute of Qingdao, Qingdao, China
| | - Huashi Guan
- Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.,Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Dongfeng Zhang
- Department of Epidemiology and Health Statistics, The School of Public Health of Qingdao University, Qingdao, China
| | - Yongjun Mao
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
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29
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Wang S, Feng W, Liu J, Wang X, Zhong L, Lv C, Feng M, An N, Mao Y. Alginate oligosaccharide alleviates senile osteoporosis via the RANKL-RANK pathway in D-galactose-induced C57BL/6J mice. Chem Biol Drug Des 2021; 99:46-55. [PMID: 34145772 PMCID: PMC9544009 DOI: 10.1111/cbdd.13904] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 06/06/2021] [Indexed: 11/30/2022]
Abstract
Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density (BMD) and bone quality and increased bone porosity, which increase the risk of bone fracture. Inflammation, one of the important mechanisms related to aging, is associated with osteoporosis. Treatment with anti‐inflammatory agents is effective for alleviating senile osteoporosis. Alginate oligosaccharide (AOS) can prevent and treat diseases related to inflammation, oxidative stress, and immunity. This study evaluates the effect of AOS on osteoporosis and investigates the underlying mechanism. Osteoporosis model was induced by D‐galactose (D‐gal) (200 mg kg−1 day−1) for eight weeks. Three groups were administered via AOS (50, 100, and 150 mg kg−1 day−1) for four weeks, while a control group received sterile water (5 ml kg−1 day−1) for 8 weeks. The results showed that AOS improved bone density and bone microstructure in D‐gal‐induced osteoporosis mice. AOS inhibited osteoclast proliferation, probably through the suppression of receptor activator of nuclear factor‐kappa B ligand (RANKL)‐associated nuclear factor kappa B (NF‐κB) and c‐Fos signaling pathway. AOS also increased osteoprotegerin (OPG) expression and competitively inhibited the binding between RANK and RANKL in senile osteoporosis. Further, AOS decreased the secretion of serum osteocalcin and reduced bone conversion. Together, these results demonstrate the anti‐osteoporosis activity of AOS in mice with osteoporosis.
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Affiliation(s)
- Shan Wang
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Wenjing Feng
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.,Department of Epidemiology and Health Statistics, The School of Public Health of Qingdao University, Qingdao, 266021, China
| | - Jianya Liu
- Department of General Practice, Anyang District Hospital of Puyang City, Anyang, 455000, China
| | - Xufu Wang
- Department of Nuclear medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Lina Zhong
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Chengxiu Lv
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Meiping Feng
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Nina An
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Yongjun Mao
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
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30
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Bauer S, Jin W, Zhang F, Linhardt RJ. The Application of Seaweed Polysaccharides and Their Derived Products with Potential for the Treatment of Alzheimer's Disease. Mar Drugs 2021; 19:89. [PMID: 33557077 PMCID: PMC7913876 DOI: 10.3390/md19020089] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 01/30/2021] [Accepted: 02/02/2021] [Indexed: 12/12/2022] Open
Abstract
Neurodegenerative diseases are among the most widespread diseases affecting humans, and the number of patients is only rising. Seaweed polysaccharide extracts show significant neuroprotective and reparative activities. Seaweed polysaccharides might provide the next big breakthrough in neurodegenerative disease treatment. This paper reviews the applications of seaweed polysaccharides as potential treatments of neurodegenerative diseases. The particular focus is on fucoidan, ulvan, and their derivatives as potential agents to treat Alzheimer's disease. This review provides a critical update on the progress in this important research area.
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Affiliation(s)
- Sarah Bauer
- Center for Biotechnology and Interdisciplinary Studies, Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
| | - Weihua Jin
- Center for Biotechnology and Interdisciplinary Studies, Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China
| | - Fuming Zhang
- Center for Biotechnology and Interdisciplinary Studies, Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
| | - Robert J Linhardt
- Center for Biotechnology and Interdisciplinary Studies, Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
- Center for Biotechnology and Interdisciplinary Studies, Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
- Center for Biotechnology and Interdisciplinary Studies, Departments of Biological Science, Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
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31
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Wan YJ, Wang YH, Guo Q, Jiang Y, Tu PF, Zeng KW. Protocatechualdehyde protects oxygen-glucose deprivation/reoxygenation-induced myocardial injury via inhibiting PERK/ATF6α/IRE1α pathway. Eur J Pharmacol 2021; 891:173723. [PMID: 33159933 DOI: 10.1016/j.ejphar.2020.173723] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 10/30/2020] [Accepted: 11/01/2020] [Indexed: 01/31/2023]
Abstract
Endoplasmic reticulum (ER) stress has been considered as a promising strategy in developing novel therapeutic agents for cardiovascular diseases through inhibiting cardiomyocyte apoptosis. Protocatechualdehyde (PCA) is a natural phenolic compound from medicinal plant Salvia miltiorrhiza with cardiomyocyte protection. However, the potential mechanism of PCA on cardiovascular ischemic injury is largely unexplored. Here, we found that PCA exerted markedly anti-apoptotic effect in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced H9c2 cells (Rat embryonic ventricular H9c2 cardiomyocytes), which was detected by 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT), lactate dehydrogenase (LDH), Hoechst 33258 and acridine orange/ethidium bromide (AO/EB) assays. PCA also obviously protected cardiomyocytes in myocardial fibrosis model of mice, which was determined by hematoxylin-eosin (HE) staining and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining. Transcriptomics coupled with bioinformatics analysis revealed a complex pharmacological signaling network especially for PCA-mediated ER stress on cardiomyocytes. Further mechanism study suggested that PCA suppressed ER stress via inhibiting protein kinase R-like ER kinase (PERK), inositol-requiring enzyme1α (IRE1α), and transcription factor 6α (ATF6α) signaling pathway through Western blot, DIOC6 and ER-Tracker Red staining, leading to a protective effect against ER stress-mediated cardiomyocyte apoptosis. Taken together, our observations suggest that PCA is a major component from Salvia miltiorrhiza against cardiovascular ischemic injury by suppressing ER stress-associated PERK, IRE1α and ATF6α signaling pathways.
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Affiliation(s)
- Yan-Jun Wan
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
| | - Yan-Hang Wang
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
| | - Qiang Guo
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
| | - Yong Jiang
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
| | - Peng-Fei Tu
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
| | - Ke-Wu Zeng
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
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Bi F, Xu Y, Chen G, Wang P. Anti-inflammatory and Anti-endoplasmic reticulum stress Effects of catalpol Against myocardial ischemia-reperfusion injury in streptozotocin-induced diabetic rats. AN ACAD BRAS CIENC 2020; 92:e20191148. [PMID: 33237136 DOI: 10.1590/0001-3765202020191148] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 01/14/2020] [Indexed: 01/19/2023] Open
Abstract
The current study was designed to investigate the effects and the mechanism of catalpol on myocardial ischemia-reperfusion (MI/R) injury in a diabetic rat model. Male Sprague-Dawley rats were divided into DM + sham, DM +I/R, and DM +I/R + C groups and diabetes was induced using single injections of streptozotocin (STZ; 70 mg/kg; i.p). After confirming the induction of diabetes, rats were administered physiological saline and catalpol (10 mg/kg; i.p.) daily for 28 days. Subsequently, rats were subjected to left anterior descending (LAD) coronary artery occlusion for 30 min followed by reperfusion for 2 h. Haemodynamic parameters were recorded throughout surgery, and following sacrifice, hearts were isolated for biochemical, histopathological, and molecular analyses. Catalpol treatment significantly ameliorated MI/R injury by improving cardiac function, normalizing myocardial enzyme activities and markers of oxidative stress, and by maintaining myocardial architecture. Furthermore, expression levels of the inflammatory cytokines TNF-α and IL-6 were decreased in biochemical and immunohistochemical studies. Additionally, the cardioprotective effects of catalpol were partly related to reductions in myocardial endoplasmic reticulum stress (ERS). In conclusion, catalpol exerts cardioprotective effects in diabetic rats by attenuating inflammation and inhibiting ERS.
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Affiliation(s)
- Fangjie Bi
- Heart Center, Zibo Central Hospital, 255400 Shandong, China
| | - Yujia Xu
- Department of Echocardiography, Zibo Central Hospital, 255400 Shandong, China
| | - Guangxin Chen
- Department of Emergency, Zibo Central Hospital, 255400 Shandong, China
| | - Pan Wang
- Department of Pain Treatment, Zibo Central Hospital, 255400 Shandong, China
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Feng W, Yang X, Feng M, Pan H, Liu J, Hu Y, Wang S, Zhang D, Ma F, Mao Y. Alginate Oligosaccharide Prevents against D-galactose-mediated Cataract in C57BL/6J Mice via Regulating Oxidative Stress and Antioxidant System. Curr Eye Res 2020; 46:802-810. [PMID: 33153341 DOI: 10.1080/02713683.2020.1842456] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
PURPOSE Alginate oligosaccharides (AOS), obtained from depolymerizing alginate, has multiple pharmacological benefits. Cataract is a common disease caused by turbidity of the lens protein due to lens metabolism disorders. This study aimed to test the effects and the underlying mechanisms of AOS on D-galactose (D-gal)-mediated cataract. MATERIALS AND METHODS A total of 45 8-week-old C57BL/6 J male mice were randomly divided into 5 groups. After eight weeks' intervention, the score of cataract was calculated depending on the turbidity of the lens. Hematoxylin and eosin (HE) and transmission electron microscope (TEM) images were observed. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were measured by corresponding detection kits, respectively. SOD1, SOD2, catalase (CAT) and p53 protein expressions were examined by Western blot. Nuclear factor erythroid-2 related factor (Nrf2) and heme oxygenase-1 (HO-1) mRNA expressions were examined by Quantitative Real Time-PCR (RT-qPCR). RESULTS The score of the turbidity of the lens showed that AOS significantly delayed the cataractogenesis. HE staining and TEM imaging showed that AOS decreased the damage and senescence of lenses in D-gal-induced C57BL/6 J mice. We further detected aging marker p53 expression in crystalline lenses, and our result showed that AOS significantly inhibited p53 protein expression in D-gal-induced mice. In addition, SOD activity and MDA level detection results showed that AOS significantly increased the activity of SOD, and decreased the level of MDA in crystalline lenses homogenates of D-gal-induced aging mice. Western blot results showed that AOS attenuated the damage of D-gal in the protein expressions of antioxidative enzymes SOD1, SOD2 and CAT. RT-qPCR results showed that AOS suppressed the down-regulation of Nrf2 and HO-1 mRNA expressions induced by D-gal. CONCLUSIONS AOS prevents against D-gal-mediated cataract in C57BL/6 J mice via inhibiting oxidative stress and up-regulating antioxidant system. Consequently, our results suggest that AOS may be an effective therapeutic strategy against cataract.
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Affiliation(s)
- Wenjing Feng
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.,Department of Epidemiology and Health Statistics, The School of Public Health of Qingdao University, Qingdao, Shandong, China
| | - Xuejiao Yang
- Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Meiping Feng
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Hui Pan
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jianya Liu
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yi Hu
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shan Wang
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Dongfeng Zhang
- Department of Epidemiology and Health Statistics, The School of Public Health of Qingdao University, Qingdao, Shandong, China
| | - Fenghua Ma
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yongjun Mao
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
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Zhao J, Han Y, Wang Z, Zhang R, Wang G, Mao Y. Alginate oligosaccharide protects endothelial cells against oxidative stress injury via integrin-α/FAK/PI3K signaling. Biotechnol Lett 2020; 42:2749-2758. [DOI: 10.1007/s10529-020-03010-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 09/19/2020] [Indexed: 01/02/2023]
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Xing M, Cao Q, Wang Y, Xiao H, Zhao J, Zhang Q, Ji A, Song S. Advances in Research on the Bioactivity of Alginate Oligosaccharides. Mar Drugs 2020; 18:E144. [PMID: 32121067 PMCID: PMC7142810 DOI: 10.3390/md18030144] [Citation(s) in RCA: 138] [Impact Index Per Article: 27.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 02/22/2020] [Accepted: 02/25/2020] [Indexed: 12/12/2022] Open
Abstract
Alginate is a natural polysaccharide present in various marine brown seaweeds. Alginate oligosaccharide (AOS) is a degradation product of alginate, which has received increasing attention due to its low molecular weight and promising biological activity. The wide-ranging biological activity of AOS is closely related to the diversity of their structures. AOS with a specific structure and distinct applications can be obtained by different methods of alginate degradation. This review focuses on recent advances in the biological activity of alginate and its derivatives, including their anti-tumor, anti-oxidative, immunoregulatory, anti-inflammatory, neuroprotective, antibacterial, hypolipidemic, antihypertensive, and hypoglycemic properties, as well as the ability to suppress obesity and promote cell proliferation and regulate plant growth. We hope that this review will provide theoretical basis and inspiration for the high-value research developments and utilization of AOS-related products.
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Affiliation(s)
- Maochen Xing
- Marine College, Shandong University, Weihai 264209, China; (M.X.); (Q.C.); (Y.W.); (H.X.); (J.Z.); (Q.Z.); (A.J.)
| | - Qi Cao
- Marine College, Shandong University, Weihai 264209, China; (M.X.); (Q.C.); (Y.W.); (H.X.); (J.Z.); (Q.Z.); (A.J.)
| | - Yu Wang
- Marine College, Shandong University, Weihai 264209, China; (M.X.); (Q.C.); (Y.W.); (H.X.); (J.Z.); (Q.Z.); (A.J.)
| | - Han Xiao
- Marine College, Shandong University, Weihai 264209, China; (M.X.); (Q.C.); (Y.W.); (H.X.); (J.Z.); (Q.Z.); (A.J.)
| | - Jiarui Zhao
- Marine College, Shandong University, Weihai 264209, China; (M.X.); (Q.C.); (Y.W.); (H.X.); (J.Z.); (Q.Z.); (A.J.)
| | - Qing Zhang
- Marine College, Shandong University, Weihai 264209, China; (M.X.); (Q.C.); (Y.W.); (H.X.); (J.Z.); (Q.Z.); (A.J.)
| | - Aiguo Ji
- Marine College, Shandong University, Weihai 264209, China; (M.X.); (Q.C.); (Y.W.); (H.X.); (J.Z.); (Q.Z.); (A.J.)
- School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
| | - Shuliang Song
- Marine College, Shandong University, Weihai 264209, China; (M.X.); (Q.C.); (Y.W.); (H.X.); (J.Z.); (Q.Z.); (A.J.)
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Zhao Y, Zhang P, Ge W, Feng Y, Li L, Sun Z, Zhang H, Shen W. Alginate oligosaccharides improve germ cell development and testicular microenvironment to rescue busulfan disrupted spermatogenesis. Am J Cancer Res 2020; 10:3308-3324. [PMID: 32194870 PMCID: PMC7053202 DOI: 10.7150/thno.43189] [Citation(s) in RCA: 90] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 01/22/2020] [Indexed: 12/22/2022] Open
Abstract
Rationale: Busulfan is currently an indispensable anti-cancer drug, particularly for children, but the side effects on male reproduction are so serious that critical drug management is needed to minimize any negative impact. Meanwhile, alginate oligosaccharides (AOS) are natural products with many consequent advantages, that have attracted a great deal of pharmaceutical attention. In the current investigation, we performed single-cell RNA sequencing on murine testes treated with busulfan and/or AOS to define the mitigating effects of AOS on spermatogenesis at the single cell level. Methods: Testicular cells (in vivo) were examined by single cell RNA sequencing analysis, histopathological analysis, immunofluorescence staining, and Western blotting. Testes samples (ex vivo) underwent RNA sequencing analysis. Blood and testicular metabolomes were determined by liquid chromatography-mass spectrometry (LC/MS). Results: We found that AOS increased murine sperm concentration and motility, and rescued busulfan disrupted spermatogenesis through improving (i) the proportion of germ cells, (ii) gene expression important for spermatogenesis, and (iii) transcriptional factors in vivo. Furthermore, AOS promoted the ex vivo expression of genes important for spermatogenesis. Finally, our results showed that AOS improved blood and testis metabolomes as well as the gut microbiota to support the recovery of spermatogenesis. Conclusions: AOS could be used to improve fertility in patients undergoing chemotherapy and to combat other factors that induce infertility in humans.
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Zhang YH, Shao Y, Jiao C, Yang QM, Weng HF, Xiao AF. Characterization and Application of an Alginate Lyase, Aly1281 from Marine Bacterium Pseudoalteromonas carrageenovora ASY5. Mar Drugs 2020; 18:E95. [PMID: 32023889 PMCID: PMC7073683 DOI: 10.3390/md18020095] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 01/28/2020] [Accepted: 01/30/2020] [Indexed: 12/13/2022] Open
Abstract
Alginate extracted from widely cultured brown seaweed can be hydrolyzed by alginate lyase to produce alginate oligosaccharides (AOS) with intriguing biological activities. Herein, a novel alginate lyase Aly1281 was cloned from marine bacterium Pseudoalteromonas carrageenovora ASY5 isolated from mangrove soil and found to belong to polysaccharide lyase family 7. Aly1281 exhibited maximum activity at pH 8.0 and 50 °C and have broad substrate specificity for polyguluronate and polymannuronate. Compared with other alginate lyases, Aly1281 exhibited high degradation specificity and mainly produced di-alginate oligosaccharides which displayed good antioxidant function to reduce ferric and scavenge radicals such as hydroxyl, ABTS+ and DPPH. Moreover, the catalytic activity and kinetic performance of Aly1281 were highly improved with the addition of salt, demonstrating a salt-activation property. A putative conformational structural feature of Aly1281 was found by MD simulation analysis for understanding the salt-activation effect.
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Affiliation(s)
- Yong-Hui Zhang
- College of Food and Biological Engineering, Jimei University, Xiamen 361021, China; (Y.-H.Z.); (Y.S.); (C.J.); (Q.-M.Y.); (H.-F.W.)
- Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Xiamen 361021, China
- Xiamen Key Laboratory of Marine Functional Food, Xiamen 361021, China
| | - Yuan Shao
- College of Food and Biological Engineering, Jimei University, Xiamen 361021, China; (Y.-H.Z.); (Y.S.); (C.J.); (Q.-M.Y.); (H.-F.W.)
- Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Xiamen 361021, China
- Xiamen Key Laboratory of Marine Functional Food, Xiamen 361021, China
| | - Chao Jiao
- College of Food and Biological Engineering, Jimei University, Xiamen 361021, China; (Y.-H.Z.); (Y.S.); (C.J.); (Q.-M.Y.); (H.-F.W.)
- Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Xiamen 361021, China
- Xiamen Key Laboratory of Marine Functional Food, Xiamen 361021, China
| | - Qiu-Ming Yang
- College of Food and Biological Engineering, Jimei University, Xiamen 361021, China; (Y.-H.Z.); (Y.S.); (C.J.); (Q.-M.Y.); (H.-F.W.)
- Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Xiamen 361021, China
- Xiamen Key Laboratory of Marine Functional Food, Xiamen 361021, China
| | - Hui-Fen Weng
- College of Food and Biological Engineering, Jimei University, Xiamen 361021, China; (Y.-H.Z.); (Y.S.); (C.J.); (Q.-M.Y.); (H.-F.W.)
- Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Xiamen 361021, China
- Xiamen Key Laboratory of Marine Functional Food, Xiamen 361021, China
| | - An-Feng Xiao
- College of Food and Biological Engineering, Jimei University, Xiamen 361021, China; (Y.-H.Z.); (Y.S.); (C.J.); (Q.-M.Y.); (H.-F.W.)
- Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Xiamen 361021, China
- Xiamen Key Laboratory of Marine Functional Food, Xiamen 361021, China
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Feng W, Hu Y, An N, Feng Z, Liu J, Mou J, Hu T, Guan H, Zhang D, Mao Y. Alginate Oligosaccharide Alleviates Monocrotaline-Induced Pulmonary Hypertension via Anti-Oxidant and Anti-Inflammation Pathways in Rats. Int Heart J 2020; 61:160-168. [PMID: 31956132 DOI: 10.1536/ihj.19-096] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Pulmonary arterial hypertension (PAH) is a serious and fatal cardiovascular disorder characterized by increased pulmonary vascular resistance and progressive pulmonary vascular remodeling. The underlying pathological mechanisms of PAH are multi-factorial and multi-cellular. Alginate oligosaccharide (AOS), which is produced by depolymerizing alginate, shows better pharmacological activities and beneficial effects. The present study was undertaken to investigate the effects and potential mechanisms of AOS-mediated alleviation of pulmonary hypertension. Pulmonary hypertension was induced in Sprague-Dawley rats by a single intraperitoneal injection of monocrotaline (MCT; 60 mg/kg). Five weeks after the injection of MCT, AOS (5, 10, and 20 mg·kg-1·d-1) was injected intraperitoneally for another three weeks. The results showed that AOS prevented the development of MCT-induced pulmonary hypertension and right ventricular hypertrophy in a dose-dependent manner. AOS treatment also prevented MCT-induced pulmonary vascular remodeling via inhibition of the TGF-β1/p-Smad2 signaling pathway. Furthermore, AOS treatment downregulated the expression of malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase, and pro-inflammatory cytokines, decreased macrophage infiltration, and upregulated the expression of anti-inflammatory cytokines. These findings indicate that AOS exerts anti-oxidative and anti-inflammatory effects in pulmonary arteries, which may contribute to the alleviation of pulmonary hypertension and pulmonary vascular remodeling.
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Affiliation(s)
- Wenjing Feng
- Department of Geriatrics, The Affiliated Hospital of Qingdao University.,Department of Epidemiology and Health Statistics, The School of Public Health of Qingdao University.,College of Medicine, University of Illinois at Chicago
| | - Yi Hu
- Department of Geriatrics, The Affiliated Hospital of Qingdao University
| | - Nina An
- Department of Geriatrics, The Affiliated Hospital of Qingdao University
| | - Zhe Feng
- Department of Geriatrics, The Affiliated Hospital of Qingdao University
| | - Jianya Liu
- Department of Geriatrics, The Affiliated Hospital of Qingdao University
| | - Jie Mou
- Department of Geriatrics, The Affiliated Hospital of Qingdao University
| | - Ting Hu
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China.,Laboratory for Marine Drugs and Bioproducts, Innovation Center for Marine Drugs Screening and Evaluation, Qingdao National Laboratory for Marine Science and Technology
| | - Huashi Guan
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China.,Laboratory for Marine Drugs and Bioproducts, Innovation Center for Marine Drugs Screening and Evaluation, Qingdao National Laboratory for Marine Science and Technology
| | - Dongfeng Zhang
- Department of Epidemiology and Health Statistics, The School of Public Health of Qingdao University
| | - Yongjun Mao
- Department of Geriatrics, The Affiliated Hospital of Qingdao University
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Guan G, Yang L, Huang W, Zhang J, Zhang P, Yu H, Liu S, Gu X. Mechanism of interactions between endoplasmic reticulum stress and autophagy in hypoxia/reoxygenation‑induced injury of H9c2 cardiomyocytes. Mol Med Rep 2019; 20:350-358. [PMID: 31115545 PMCID: PMC6580049 DOI: 10.3892/mmr.2019.10228] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 04/25/2019] [Indexed: 12/13/2022] Open
Abstract
Endoplasmic reticulum (ER) stress and autophagy are involved in myocardial ischemia‑reperfusion (I/R) injury; however, their roles in this type of injury remain unclear. The present study investigated the roles of ER stress and autophagy, and their underlying mechanisms, in H9c2 cells during hypoxia/reoxygenation (H/R) injury. Cell viability was detected by CCK‑8 assay. The autophagy flux was monitored with mCherry‑GFP‑LC3‑adenovirus transfection. The expression levels of autophagy‑related proteins and ER stress‑related proteins were measured by western blotting. Apoptosis was detected by flow cytometry and western blotting. The results indicated that autophagy was induced, ER stress was activated and apoptosis was promoted in H9c2 cells during H/R injury. The inhibition of ER stress by 4‑phenylbutyrate or C/EBP homologous protein (CHOP)‑targeting small interfering RNA (siRNA) decreased autophagy and ameliorated cell apoptosis during H/R injury. Activation of autophagy by rapamycin attenuated ER stress and ameliorated cell apoptosis. Inhibition of autophagy by 3‑methyladenine or Beclin1‑targeting siRNA aggravated ER stress and exacerbated cell apoptosis, and activation of ER stress by thapsigargin decreased autophagy and induced cell apoptosis. Collectively, the findings of the present study demonstrated that H/R induced apoptosis and autophagy via ER stress in H9c2 cells, and that CHOP may serve an important role in ER stress‑induced autophagy and apoptosis. Autophagy, as an adaptive response, was activated by ER stress and alleviated ER stress‑induced cell apoptosis during H/R injury.
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Affiliation(s)
- Gaopeng Guan
- Department of Cardiology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
- Key Laboratory of System Bio-Medicine of Jiangxi Province, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
- Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Lei Yang
- Key Laboratory of System Bio-Medicine of Jiangxi Province, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
- Basic Medical Science College, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
| | - Wenyin Huang
- Department of Cardiology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
| | - Jun Zhang
- Department of Cardiology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
| | - Puhua Zhang
- Department of Cardiology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
| | - Huan Yu
- Key Laboratory of System Bio-Medicine of Jiangxi Province, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
- Basic Medical Science College, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
| | - Shengyuan Liu
- Department of Cardiology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
- Key Laboratory of System Bio-Medicine of Jiangxi Province, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
| | - Xiang Gu
- Department of Cardiology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
- Key Laboratory of System Bio-Medicine of Jiangxi Province, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
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Alginate oligosaccharide attenuates α2,6-sialylation modification to inhibit prostate cancer cell growth via the Hippo/YAP pathway. Cell Death Dis 2019; 10:374. [PMID: 31076566 PMCID: PMC6510775 DOI: 10.1038/s41419-019-1560-y] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 03/23/2019] [Accepted: 03/26/2019] [Indexed: 12/11/2022]
Abstract
Chitosan oligosaccharides have been reported to inhibit various tumors. However, the water-soluble marine plant oligosaccharide alginate oligosaccharide (AOS) has only rarely been reported to have anti-cancer effects. Moreover, the inhibitory effect of AOS on prostate cancer and the underlying molecular mechanism remain unknown. This study shows that AOS inhibited cell growth, which was consistent with the attenuation of α2,6-sialylation modification. Furthermore, AOS inhibited ST6Gal-1 promoter activity and thus affected transcriptional processes. In addition, AOS could activate the Hippo/YAP pathway and block the recruitment of both the coactivator YAP and c-Jun. Furthermore, YAP interacted with the transcription factor c-Jun and regulated the transcriptional activity of the downstream target ST6Gal-1 gene. Consistent with in vitro data, AOS suppressed the tumorigenicity of prostate cancer cells via the Hippo/YAP pathway in vivo. In summary, these data indicate that AOS slows the proliferation of prostate cancer and provides a basis for the healthy function of kelp in traditional cognition.
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Belik AA, Silchenko AS, Kusaykin MI, Zvyagintseva TN, Ermakova SP. Alginate Lyases: Substrates, Structure, Properties, and Prospects of Application. RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY 2018. [DOI: 10.1134/s1068162018040040] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Xiao J, Ke ZP, Shi Y, Zeng Q, Cao Z. The cardioprotective effect of thymoquinone on ischemia-reperfusion injury in isolated rat heart via regulation of apoptosis and autophagy. J Cell Biochem 2018; 119:7212-7217. [PMID: 29932232 DOI: 10.1002/jcb.26878] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2017] [Accepted: 03/21/2018] [Indexed: 12/14/2022]
Abstract
Thymoquinone (TQ), as the active constituents of black cumin (Nigella sativa) seed oil, has been reported to have potential protective effects on the cardiovascular system. This study aimed to investigate the effects and the underlying mechanisms of TQ on myocardial ischemia-reperfusion (I/R) injury in Langendorff-perfused rat hearts. Wister rat hearts were subjected to I/R and the experimental group were pretreated with TQ prior to I/R. Hemodynamic parameters, myocardial infarct size, cardiac marker enzymes, superoxide dismutase (SOD), malondialdehyde (MDA) content, and cardiomyocyte apoptosis were assayed. Compared with the untreated group, TQ preconditioning significantly improved cardiac function, reduced infarct size, decreased cardiac lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) levels, suppressed enedoxidative stress, and apoptosis. In addition, TQ treatment promoted autophagy, which was partially reversed by chloroquine (CQ), a kind of autophagy blocker. Our study suggests that TQ can protect heart against I/R injury, which is associated with anti-oxidative and anti-apoptotic effects through activation of autophagy.
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Affiliation(s)
- Junhui Xiao
- Department of Cardiology, Huadu District People's Hospital, Southern Medical University, Guangzhou, China
| | - Zun-Ping Ke
- Department of Cardiology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Yan Shi
- The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China
| | - Qiutang Zeng
- Department of Cardiology, Huadu District People's Hospital, Southern Medical University, Guangzhou, China
| | - Zhe Cao
- Department of Cardiology，The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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