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Zhou S, Zhou P, Yang T, Si J, An W, Jiang Y. Glucosamine supplementation contributes to reducing the risk of type 2 diabetes: Evidence from Mendelian randomization combined with a meta-analysis. J Int Med Res 2025; 53:3000605251334460. [PMID: 40300556 PMCID: PMC12041707 DOI: 10.1177/03000605251334460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 03/21/2025] [Indexed: 05/01/2025] Open
Abstract
ObjectiveObservational studies on glucosamine supplementation and type 2 diabetes risk have shown inconsistent results, necessitating the use of Mendelian randomization to clarify the true causal relationship.MethodsThe glucosamine supplementation-related genome-wide association study dataset was obtained from the MRC Integrative Epidemiology Unit consortium, whereas type 2 diabetes-related genome-wide association study datasets were obtained from the FinnGen consortium (discovery) and Xue et al.'s meta-analysis (validation). Two-sample Mendelian randomization analyses were performed separately in the discovery and validation datasets, followed by meta-analysis and multivariable Mendelian randomization analyses to verify the robustness of the results of two-sample Mendelian randomization. The estimation of the causal relationship was conducted through the inverse variance weighted method.ResultsGlucosamine supplementation exhibited a significant protective effect against type 2 diabetes, as identified by two-sample Mendelian randomization analysis in the FinnGen consortium (odds ratio: 0.13, 95% confidence interval: 0.02-0.89) and validated in Xue et al.'s meta-analysis (odds ratio: 0.06, 95%; confidence interval: 0.01-0.29). A combined meta-analysis (odds ratio: 0.08, 95%; confidence interval: 0.02-0.27) of the results of two-sample Mendelian randomization confirmed the robustness of these findings. Additionally, multivariable Mendelian randomization analysis (odds ratio: 0.12, 95%; confidence interval: 0.02-0.94), after adjusting for confounding factors, supported the results of two-sample Mendelian randomization. No evidence of heterogeneity or pleiotropy was observed.ConclusionOverall, our results revealed that genetically predicted glucosamine supplementation was inversely associated with the risk of type 2 diabetes, highlighting the potential importance of glucosamine supplementation in preventing type 2 diabetes.
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Affiliation(s)
- Shuai Zhou
- Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, China
| | - Peiwen Zhou
- Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, China
| | - Tianshi Yang
- Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, China
| | - Junzhuo Si
- Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, China
| | - Wenyan An
- Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, China
| | - Yanfang Jiang
- Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, China
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Cheng ZJ, Luo YF, Zhu QY, Wang YF, Ren WY, Deng FY, Bo L, Jiang XY, Lei SF, Wu LF. Association of habitual glucosamine use with risk of microvascular complications among individuals with type 2 diabetes: a prospective cohort study in UK biobank. Nutr Diabetes 2025; 15:12. [PMID: 40169583 PMCID: PMC11961739 DOI: 10.1038/s41387-025-00369-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 02/12/2025] [Accepted: 02/28/2025] [Indexed: 04/03/2025] Open
Abstract
BACKGROUND Glucosamine is a widely used supplement for treating osteoarthritis and joint pain. New evidence suggests a potential association between glucosamine and type 2 diabetes, inflammation and cardiometabolic risk. We aimed to prospectively evaluate the association of habitual glucosamine use with risk of diabetic microvascular complications based on data from the large-scale nationwide prospective UK Biobank cohort study. METHODS This analysis included 21,171 participants with type 2 diabetes who were free of microvascular complications from the UK Biobank. Incidence of diabetic microvascular complications was ascertained via electronic health records. The Cox proportional hazards model was used to assess the relationship between glucosamine use and the risk of diabetic microvascular complications. Subgroup analyses and sensitivity analyses were performed to explore the potential effect modifications and the robustness of the main findings. RESULTS At baseline, 14.5% of the participants reported habitual use of glucosamine supplements. During a median follow-up of 12.3 years, 4399 people developed diabetic microvascular complications, including 2084 cases of incident diabetic nephropathy, 2401 incident diabetic retinopathy, and 831 incident diabetic neuropathy. Glucosamine use was significantly associated with lower risks of composite microvascular complications (hazard ratio (HR) 0.89, 95% CI: 0.81 to 0.97) and diabetic nephropathy (HR 0.87, 95% CI: 0.76 to 0.98) in fully adjusted models. However, there was no significant inverse association between glucosamine use and the risk of diabetic retinopathy (HR 0.94, 95% CI: 0.83 to 1.06) or diabetic neuropathy (HR 0.88, 95% CI: 0.71 to 1.08). CONCLUSIONS Habitual use of glucosamine supplement was significantly associated with lower risks of composite microvascular complications and diabetic nephropathy but not retinopathy or neuropathy in individuals with type 2 diabetes.
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Affiliation(s)
- Zi-Jian Cheng
- Center for Genetic Epidemiology and Genomics, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, China
| | - Yu-Feng Luo
- Center for Genetic Epidemiology and Genomics, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, China
| | - Qing-Yun Zhu
- Center for Genetic Epidemiology and Genomics, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, China
| | - Yan-Fei Wang
- Center for Genetic Epidemiology and Genomics, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, China
| | - Wen-Yan Ren
- Cambridge-Suda Genomic Resource Center, Jiangsu Key Laboratory of Neuropsychiatric Diseases, Medical College of Soochow University, Suzhou, China
| | - Fei-Yan Deng
- Center for Genetic Epidemiology and Genomics, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, China
| | - Lin Bo
- Department of Rheumatology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Xi-Yuan Jiang
- Center of Osteoporosis, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, China.
| | - Shu-Feng Lei
- Center for Genetic Epidemiology and Genomics, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, China.
| | - Long-Fei Wu
- Center for Genetic Epidemiology and Genomics, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, China.
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Largo R, Mediero A, Villa-Gomez C, Bermejo-Alvarez I, Herrero-Beaumont G. Aberrant anabolism hinders constructive metabolism of chondrocytes by pharmacotherapy in osteoarthritis. Bone Joint Res 2025; 14:199-207. [PMID: 40042132 PMCID: PMC11881514 DOI: 10.1302/2046-3758.143.bjr-2024-0241.r1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/03/2025] Open
Abstract
Osteoarthritis (OA) is a highly prevalent and disabling disease with an unmet therapeutic need. The characteristic cartilage loss and alteration of other joint structures result from a complex interaction of multiple risk factors, with mechanical overload consistently playing a central role. This overload generates an inflammatory response in the cartilage due to the activation of the innate immune response in chondrocytes, which occurs through various cellular mechanisms. Moreover, risk factors associated with obesity, being overweight, and metabolic syndrome enhance the inflammatory response both locally and systemically. OA chondrocytes, the only cells present in articular cartilage, are therefore inflamed and initiate an anabolic process in an attempt to repair the damaged tissue, which ultimately results in an aberrant and dysfunctional process. Under these circumstances, where the cartilage continues to be subjected to chronic mechanical stress, proposing a treatment that stimulates the chondrocytes' anabolic response to restore tissue structure does not appear to be a therapeutic target with a high likelihood of success. In fact, anabolic drugs proposed for the treatment of OA have yet to demonstrate efficacy. By contrast, multiple therapeutic strategies focused on pharmacologically managing the inflammatory component, both at the joint and systemic levels, have shown promise. Therefore, prioritizing the control of chronic innate pro-inflammatory pathways presents the most viable and promising therapeutic strategy for the effective management of OA. As research continues, this approach may offer the best opportunity to alleviate the burden of this incapacitating disease.
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Affiliation(s)
- Raquel Largo
- Joint and Bone Research Unit, Service of Rheumatology, IIS Fundación Jiménez Díaz UAM, Madrid, Spain
| | - Aranzazu Mediero
- Joint and Bone Research Unit, Service of Rheumatology, IIS Fundación Jiménez Díaz UAM, Madrid, Spain
| | - Cristina Villa-Gomez
- Joint and Bone Research Unit, Service of Rheumatology, IIS Fundación Jiménez Díaz UAM, Madrid, Spain
| | - Ismael Bermejo-Alvarez
- Joint and Bone Research Unit, Service of Rheumatology, IIS Fundación Jiménez Díaz UAM, Madrid, Spain
| | - Gabriel Herrero-Beaumont
- Joint and Bone Research Unit, Service of Rheumatology, IIS Fundación Jiménez Díaz UAM, Madrid, Spain
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Del Río E. Rethinking Osteoarthritis Management: Synergistic Effects of Chronoexercise, Circadian Rhythm, and Chondroprotective Agents. Biomedicines 2025; 13:598. [PMID: 40149577 PMCID: PMC11940269 DOI: 10.3390/biomedicines13030598] [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: 12/23/2024] [Revised: 02/13/2025] [Accepted: 02/17/2025] [Indexed: 03/29/2025] Open
Abstract
Osteoarthritis (OA) is a chronic and debilitating joint disease characterized by progressive cartilage degeneration for which no definitive cure exists. Conventional management approaches often rely on fragmented and poorly coordinated pharmacological and non-pharmacological interventions that are inconsistently applied throughout the disease course. Persistent controversies regarding the clinical efficacy of chondroprotective agents, frequently highlighted by pharmacovigilance agencies, underscore the need for a structured evidence-based approach. Emerging evidence suggests that synchronizing pharmacotherapy and exercise regimens with circadian biology may optimize therapeutic outcomes by addressing early pathological processes, including low-grade inflammation, oxidative stress, and matrix degradation. Recognizing the influence of the chondrocyte clock on these processes, this study proposes a 'prototype' for a novel framework that leverages the circadian rhythm-aligned administration of traditional chondroprotective agents along with tailored, accessible exercise protocols to mitigate cartilage breakdown and support joint function. In addition, this model-based framework emphasizes the interdependence between cartilage chronobiology and time-of-day-dependent responses to exercise, where strategically timed joint activity enhances nutrient and waste exchange, mitigates mitochondrial dysfunction, supports cellular metabolism, and promotes tissue maintenance, whereas nighttime rest promotes cartilage rehydration and repair. This time-sensitive, comprehensive approach aims to slow OA progression, reduce structural damage, and delay invasive procedures, particularly in weight-bearing joints such as the knee and hip. However, significant challenges remain, including inter-individual variability in circadian rhythms, a lack of reliable biomarkers for pharmacotherapeutic monitoring, and limited clinical evidence supporting chronoexercise protocols. Future large-scale, longitudinal trials are critical to evaluate the efficacy and scalability of this rational integrative strategy, paving the way for a new era in OA management.
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Rajasekaran S, Ramachandran K, K S SVA, Kanna RM, Shetty AP. From Modic to Disc Endplate Bone Marrow Complex - The Natural Course and Clinical Implication of Vertebral Endplate Changes. Global Spine J 2025; 15:196-209. [PMID: 39090550 PMCID: PMC11571513 DOI: 10.1177/21925682241271440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 07/01/2024] [Accepted: 07/23/2024] [Indexed: 08/04/2024] Open
Abstract
STUDY DESIGN Review article. OBJECTIVES A review of literature on the epidemiology, natural course, pathobiology and clinical implications of vertebral endplate changes. METHODS A literature search was performed using the Cochrane Database of Systematic Reviews, EMBASE, and PubMed. Studies published over the last 10 years were analysed. The searches were performed using Medical Subject Headings terms, and the subheadings used were "Vertebral endplate changes", "Modic changes", "Disc Endplate Bone Marrow complex". RESULTS The disc, endplate (EP), and bone marrow region of the spine constitute a unified morphological and functional unit, with isolated degeneration of any one structure being uncommon. Disc degeneration causes endplate defects, which result in direct communication and a constant cross-talk between the disc and the vertebral body. This may result in a persistent inflammatory state of the vertebral bone marrow, serving as a major pain generator. This review article focuses on vertebral endplate changes and how the current understanding has progressed from the Modic classification to the Disc Endplate Bone Marrow complex classification. It provides a clear portrayal of the natural course of these alterations and their clinical implications in low back pain. CONCLUSIONS In light of the heightened interest and current prominence of vertebral endplate changes within the spine community, we must progress beyond the Modic changes to achieve a comprehensive understanding. The DEBM complex classification will play a major part in disc degeneration research and clinical care, representing a considerable advancement in our understanding of the vertebral endplate changes over the classical Modic changes.
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Affiliation(s)
| | | | | | - Rishi M. Kanna
- Department of Spine Surgery, Ganga Hospital, Coimbatore, India
| | - Ajoy P. Shetty
- Department of Spine Surgery, Ganga Hospital, Coimbatore, India
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Malaguez GG, Artuzi FE, Quevedo AS, Puricelli E, Ponzoni D. Can treatment with chondroitin and glucosamine sulphate prevent changes in the articular disc caused by temporomandibular joint osteoarthritis? J Oral Rehabil 2024; 51:2289-2296. [PMID: 39092654 DOI: 10.1111/joor.13814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 07/09/2024] [Accepted: 07/16/2024] [Indexed: 08/04/2024]
Abstract
BACKGROUND Chondroitin and glucosamine sulphates (CGS) are considered structure-modifying drugs and have been studied in the prevention, delay or reversal of structural morphological changes in joints caused by osteoarthritis. OBJECTIVE The aim of the present study was to investigate the action of CGS on the progression of chemically induced osteoarthritis in the temporomandibular joint (TMJ) of rabbits by evaluating the serum levels of tumour necrosis factor (TNF-α) and collagen in the articular discs. MATERIALS AND METHODS A sample of 36 male rabbits was divided into three groups: control (CG), osteoarthritis (OG) and treatment (TG). The disease was induced by intra-articular injection of sodium monoiodoacetate (10 mg/mL) in the OG and TG groups bilaterally. After 10 days, the TG animals received subcutaneous injection of chondroitin sulphates and glucosamine (7.5 mg/kg) and the OG and CG received saline solution (50 μL). Euthanasia times were subdivided into 40 and 100 days. Collagen quantification was performed by biochemical and histological analysis and for the quantification of serum levels of TNF-α, an enzyme immunoassay was used. RESULTS The TG showed an increase in the collagen area of the articular disc when compared to the CG and the OG. The increase collagen concentration in the discs did not show a statistically significant difference between the groups. Post-treatment TNF-α levels were significantly lower in TG compared to OG. CONCLUSIONS The results indicate that CGS treatment delayed the degeneration of the collagen in the TMJ articular disc and reduced serum TNF-α levels, indicating a preventive effect on OA progression.
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Affiliation(s)
- Giulia Giacomini Malaguez
- School of Dentistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil
| | - Felipe Ernesto Artuzi
- School of Dentistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil
| | - Alexandre Silva Quevedo
- School of Dentistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil
| | - Edela Puricelli
- School of Dentistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil
- Departament of Oral and Maxillofacial Surgery, HCPA, Porto Alegre, Rio Grande do Sul, Brazil
| | - Deise Ponzoni
- School of Dentistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil
- Departament of Oral and Maxillofacial Surgery, HCPA, Porto Alegre, Rio Grande do Sul, Brazil
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Singh I, Anand S, Gowda DJ, Kamath A, Singh AK. Caloric restriction mimetics improve gut microbiota: a promising neurotherapeutics approach for managing age-related neurodegenerative disorders. Biogerontology 2024; 25:899-922. [PMID: 39177917 PMCID: PMC11486790 DOI: 10.1007/s10522-024-10128-4] [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: 06/13/2024] [Accepted: 08/05/2024] [Indexed: 08/24/2024]
Abstract
The gut microbiota (GM) produces various molecules that regulate the physiological functionality of the brain through the gut-brain axis (GBA). Studies suggest that alteration in GBA may lead to the onset and progression of various neurological dysfunctions. Moreover, aging is one of the prominent causes that contribute to the alteration of GBA. With age, GM undergoes a shift in population size and species of microflora leading to changes in their secreted metabolites. These changes also hamper communications among the HPA (hypothalamic-pituitary-adrenal), ENS (enteric nervous system), and ANS (autonomic nervous system). A therapeutic intervention that has recently gained attention in improving health and maintaining communication between the gut and the brain is calorie restriction (CR), which also plays a critical role in autophagy and neurogenesis processes. However, its strict regime and lifelong commitment pose challenges. The need is to produce similar beneficial effects of CR without having its rigorous compliance. This led to an exploration of calorie restriction mimetics (CRMs) which could mimic CR's functions without limiting diet, providing long-term health benefits. CRMs ensure the efficient functioning of the GBA through gut bacteria and their metabolites i.e., short-chain fatty acids, bile acids, and neurotransmitters. This is particularly beneficial for elderly individuals, as the GM deteriorates with age and the body's ability to digest the toxic accumulates declines. In this review, we have explored the beneficial effect of CRMs in extending lifespan by enhancing the beneficial bacteria and their effects on metabolite production, physiological conditions, and neurological dysfunctions including neurodegenerative disorders.
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Affiliation(s)
- Ishika Singh
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Karnataka, Manipal, 576 104, India
| | - Shashi Anand
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Karnataka, Manipal, 576 104, India
| | - Deepashree J Gowda
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Karnataka, Manipal, 576 104, India
| | - Amitha Kamath
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Karnataka, Manipal, 576 104, India
| | - Abhishek Kumar Singh
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Karnataka, Manipal, 576 104, India.
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Yang J, Xiao S, Deng J, Li Y, Hu H, Wang J, Lu C, Li G, Zheng L, Wei Q, Zhong J. Oxygen vacancy-engineered cerium oxide mediated by copper-platinum exhibit enhanced SOD/CAT-mimicking activities to regulate the microenvironment for osteoarthritis therapy. J Nanobiotechnology 2024; 22:491. [PMID: 39155382 PMCID: PMC11330606 DOI: 10.1186/s12951-024-02678-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Accepted: 06/30/2024] [Indexed: 08/20/2024] Open
Abstract
Cerium oxide (CeO2) nanospheres have limited enzymatic activity that hinders further application in catalytic therapy, but they have an "oxidation switch" to enhance their catalytic activity by increasing oxygen vacancies. In this study, according to the defect-engineering strategy, we developed PtCuOX/CeO2-X nanozymes as highly efficient SOD/CAT mimics by introducing bimetallic copper (Cu) and platinum (Pt) into CeO2 nanospheres to enhance the oxygen vacancies, in an attempt to combine near-infrared (NIR) irradiation to regulate microenvironment for osteoarthritis (OA) therapy. As expected, the Cu and Pt increased the Ce3+/Ce4+ ratio of CeO2 to significantly enhance the oxygen vacancies, and simultaneously CeO2 (111) facilitated the uniform dispersion of Cu and Pt. The strong metal-carrier interaction synergy endowed the PtCuOX/CeO2-X nanozymes with highly efficient SOD/CAT-like activity by the decreased formation energy of oxygen vacancy, promoted electron transfer, the increased adsorption energy of intermediates, and the decreased reaction activation energy. Besides, the nanozymes have excellent photothermal conversion efficiency (55.41%). Further, the PtCuOX/CeO2-X antioxidant system effectively scavenged intracellular ROS and RNS, protected mitochondrial function, and inhibited the inflammatory factors, thus reducing chondrocyte apoptosis. In vivo, experiments demonstrated the biosafety of PtCuOX/CeO2-X and its potent effect on OA suppression. In particular, NIR radiation further enhanced the effects. Mechanistically, PtCuOX/CeO2-X nanozymes reduced ras-related C3 botulinum toxin substrate 1 (Rac-1) and p-p65 protein expression, as well as ROS levels to remodel the inflammatory microenvironment by inhibiting the ROS/Rac-1/nuclear factor kappa-B (NF-κB) signaling pathway. This study introduces new clinical concepts and perspectives that can be applied to inflammatory diseases.
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Affiliation(s)
- Junxu Yang
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China
- Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China
| | - Shihui Xiao
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China
- Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China
| | - Jiejia Deng
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China
- Life Sciences Institute, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China
| | - Yuquan Li
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China
- Department of Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, No. 166 East University Road, Nanning, Guangxi, 530005, People's Republic of China
| | - Hao Hu
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China
| | - Jiawei Wang
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China
| | - Chun Lu
- School of Materials and Environment, Guangxi Minzu University, Nanning, Guangxi, 53000, People's Republic of China
| | - Guanhua Li
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China
- Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China
| | - Li Zheng
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China.
| | - Qingjun Wei
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China.
- Department of Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, No. 166 East University Road, Nanning, Guangxi, 530005, People's Republic of China.
| | - Jingping Zhong
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China.
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Yang L, Li W, Zhao Y, Shang L. Magnetic Polysaccharide Mesenchymal Stem Cells Exosomes Delivery Microcarriers for Synergistic Therapy of Osteoarthritis. ACS NANO 2024; 18:20101-20110. [PMID: 39039744 DOI: 10.1021/acsnano.4c01406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/24/2024]
Abstract
Osteoarthritis (OA) is a prevalent degenerative disease that afflicts more than 250 million people worldwide, impairing their mobility and quality of life. However, conventional drug therapy is palliative. Exosomes (Exo), although with the potential to fundamentally repair cartilage, face challenges in their efficient enrichment and delivery. In this study, we developed magnetic polysaccharide hydrogel particles as microcarriers for synergistic therapy of OA. The microcarriers were composed of modified natural polysaccharides, hyaluronic acid (HAMA), and chondroitin sulfate (CSMA), and were generated from microfluidic electrospray in combination with a cryogelation process. Magnetic nanoparticles with spiny structures capable of capturing stem cell Exo were encapsulated within the microcarriers together with an anti-inflammatory drug diclofenac sodium (DS). The released DS and Exo from the microcarriers had a synergistic effect in alleviating the OA symptoms and promoting cartilage repair. The in vitro and in vivo results demonstrated the excellent performance of the microcarrier for OA treatment. We believe this work has potential for Exo therapy of OA and other related diseases.
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Affiliation(s)
- Lei Yang
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
- Oujiang Laboratory (Zhejiang Laboratory for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China
| | - Wenzhao Li
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
- Oujiang Laboratory (Zhejiang Laboratory for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China
| | - Yuanjin Zhao
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
- Oujiang Laboratory (Zhejiang Laboratory for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China
| | - Luoran Shang
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
- Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-Laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
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10
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Wu Y, Che Y, Zhang Y, Xiong Y, Shu C, Jiang J, Li G, Guo L, Qiao T, Li S, Li O, Chang N, Zhang X, Zhang M, Qiu D, Xi H, Li J, Chen X, Ye M, Zhang J. Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization study. Front Genet 2024; 15:1293668. [PMID: 38993479 PMCID: PMC11236616 DOI: 10.3389/fgene.2024.1293668] [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: 09/28/2023] [Accepted: 05/16/2024] [Indexed: 07/13/2024] Open
Abstract
Introduction Observational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation. Methods For Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments. Results Our results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34-4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32-3.43]), benign neoplasm of the larynx (2.01 [1.36-2.96]), melanoma (1.74 [1.17-2.59]), follicular lymphoma (1.50 [1.06-2.11]), autoimmune thyroiditis (2.47 [1.49-4.08]), and autoimmune hyperthyroidism (1.93 [1.17-3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland. Conclusion Casting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported.
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Affiliation(s)
- Yingtong Wu
- Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Air-Force Medical University, Xi’an, China
- First Sanatorium, Air Force Healthcare Center for Special Services, Hangzhou, China
| | - Yinggang Che
- Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Air-Force Medical University, Xi’an, China
| | - Yong Zhang
- Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Air-Force Medical University, Xi’an, China
| | - Yanlu Xiong
- Department of Thoracic Surgery, Tangdu Hospital, Air-Force Medical University, Xi’an, China
| | - Chen Shu
- Department of Thoracic Surgery, Tangdu Hospital, Air-Force Medical University, Xi’an, China
| | - Jun Jiang
- Department of Health Service, Air-Force Medical University, Xi’an, China
| | - Gaozhi Li
- 94498th Unit of the People’s Liberation Army of China, Nanyang, China
| | - Lin Guo
- Department of Obstetrics and Gynecology, Tangdu Hospital, Air-Force Medical University, Xi’an, China
| | - Tianyun Qiao
- Department of Thoracic Surgery, Tangdu Hospital, Air-Force Medical University, Xi’an, China
| | - Shuwen Li
- First Sanatorium, Air Force Healthcare Center for Special Services, Hangzhou, China
| | - Ou Li
- First Sanatorium, Air Force Healthcare Center for Special Services, Hangzhou, China
| | - Ning Chang
- Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Air-Force Medical University, Xi’an, China
| | - Xinxin Zhang
- College of Pulmonary and Critical Care Medicine, the 8th Medical Centre of Chinese PLA General Hospital, Beijing, China
| | - Minzhe Zhang
- Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Air-Force Medical University, Xi’an, China
| | - Dan Qiu
- Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Air-Force Medical University, Xi’an, China
| | - Hangtian Xi
- Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Air-Force Medical University, Xi’an, China
| | - Jinggeng Li
- Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Air-Force Medical University, Xi’an, China
| | - Xiangxiang Chen
- Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Air-Force Medical University, Xi’an, China
| | - Mingxiang Ye
- Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Jian Zhang
- Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Air-Force Medical University, Xi’an, China
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11
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Roy HS, Murugesan P, Kulkarni C, Arora M, Nagar GK, Guha R, Chattopadhyay N, Ghosh D. On-demand release of a selective MMP-13 blocker from an enzyme-responsive injectable hydrogel protects cartilage from degenerative progression in osteoarthritis. J Mater Chem B 2024; 12:5325-5338. [PMID: 38669084 DOI: 10.1039/d3tb02871b] [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: 04/28/2024]
Abstract
In osteoarthritis (OA), the degradation of cartilage is primarily driven by matrix metalloprotease-13 (MMP-13). Hence, the inhibition of MMP-13 has emerged as an attractive target for OA treatment. Among the various approaches that are being explored for MMP-13 regulation, blocking of the enzyme with specific binding molecules appears to be a more promising strategy for preventing cartilage degeneration. To enhance effectiveness and ensure patient compliance, it is preferable for the binding molecule to exhibit sustained activity when administered directly into the joint. Herein, we present an enzyme-responsive hydrogel that was designed to exhibit on-demand, the sustained release of BI-4394, a potent and highly selective MMP-13 blocker. The stable and compatible hydrogel was prepared using triglycerol monostearate. The efficacy of the hydrogel to prevent cartilage damage was assessed in a rat model of OA induced by anterior cruciate ligament transection (ACLT). The results revealed that in comparison to the rats administrated weekly with intra-articular BI-4394, the hydrogel implanted rats had reduced levels of inflammation and bone erosion. In comparison to untreated control, the cartilage in animals administered with BI-4394/hydrogel exhibited significant levels of collagen-2 and aggrecan along with reduced MMP-13. Overall, this study confirmed the potential of BI-4394 delivery using an enzyme-responsive hydrogel as a promising treatment option to treat the early stages of OA by preventing further cartilage degradation.
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Affiliation(s)
- Himadri Shekhar Roy
- Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, Sector-81, Mohali-140306, Punjab, India.
| | - Preethi Murugesan
- Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, Sector-81, Mohali-140306, Punjab, India.
| | - Chirag Kulkarni
- Division of Endocrinology and Centre for Research in ASTHI, CSIR-Central Drug Research Institute, Lucknow-226031, Uttar Pradesh, India
| | - Malika Arora
- Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, Sector-81, Mohali-140306, Punjab, India.
| | - Geet Kumar Nagar
- Division of Endocrinology and Centre for Research in ASTHI, CSIR-Central Drug Research Institute, Lucknow-226031, Uttar Pradesh, India
| | - Rajdeep Guha
- Division of Laboratory Animal Facility, CSIR-Central Drug Research Institute, Lucknow-226031, Uttar Pradesh, India
| | - Naibedya Chattopadhyay
- Division of Endocrinology and Centre for Research in ASTHI, CSIR-Central Drug Research Institute, Lucknow-226031, Uttar Pradesh, India
| | - Deepa Ghosh
- Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, Sector-81, Mohali-140306, Punjab, India.
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12
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Lehrer S, Morello T, Karrasch C, Rheinstein PH, Danias J. Effect of Glucosamine on Intraocular Pressure and Risk of Developing Glaucoma. J Glaucoma 2024; 33:240-245. [PMID: 38031296 PMCID: PMC10954404 DOI: 10.1097/ijg.0000000000002340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 11/15/2023] [Indexed: 12/01/2023]
Abstract
PRCIS Glucosamine supplementation is common but can be associated with increased intraocular pressure (IOP) and could contribute to the pathogenesis of glaucoma. It may be prudent for ophthalmologists to elicit any history of glucosamine use from their patients and advise them accordingly. Further studies on the role of glucosamine in glaucoma are warranted. BACKGROUND The most frequently recommended slow-acting medication for osteoarthritis symptoms is glucosamine, although its effectiveness is questionable. Widely used glucosamine sulfate supplements may increase IOP. METHODS In the current study, we analyzed online databases such as UK Biobank, MedWatch, and FinnGen to evaluate the relationship between glucosamine and IOP and glaucoma. We included budesonide and fluticasone in the analysis for comparison since these drugs are associated with increased IOP. RESULTS In UK Biobank subjects, glucosamine use was associated with increased corneal compensated IOP ( P =0.002, 2-tailed t test). This was also true in subjects without glaucoma ( P =0.002, 2-tailed t test). However, no significant association between glucosamine and IOP was detected in subjects with a diagnosis of glaucoma. In MedWatch, 0.21% of subjects taking glucosamine reported glaucoma, 0.29% of subjects using budesonide reported glaucoma, and 0.22% of subjects using fluticasone reported glaucoma. In contrast, 0.08% of subjects using any other drug reported glaucoma. This variability is significant ( P <0.001, 2-tailed Fisher exact test). Data from FinnGen on the risk of primary open angle glaucoma or glaucoma in subjects using glucosamine before the diagnosis of the disease revealed a significantly increased risk for both primary open angle glaucoma (hazard ratio: 2.35) and glaucoma (hazard ratio: 1.95). CONCLUSION Glucosamine supplementation is common but can be associated with increased IOP and could contribute to the pathogenesis of glaucoma. It may be prudent for ophthalmologists to elicit any history of glucosamine use from their patients and advise them accordingly. Further studies on the role of glucosamine in glaucoma are warranted.
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Affiliation(s)
- Steven Lehrer
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai
| | | | | | | | - John Danias
- Department of Ophthalmology, SUNY Downstate HSU, New York, NY
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Liu W, Liu A, Li X, Sun Z, Sun Z, Liu Y, Wang G, Huang D, Xiong H, Yu S, Zhang X, Fan C. Dual-engineered cartilage-targeting extracellular vesicles derived from mesenchymal stem cells enhance osteoarthritis treatment via miR-223/NLRP3/pyroptosis axis: Toward a precision therapy. Bioact Mater 2023; 30:169-183. [PMID: 37593145 PMCID: PMC10429745 DOI: 10.1016/j.bioactmat.2023.06.012] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 05/24/2023] [Accepted: 06/19/2023] [Indexed: 08/19/2023] Open
Abstract
Osteoarthritis (OA) is the most common disabling joint disease with no effective disease modifying drugs. Extracellular vesicles released by several types of mesenchymal stem cells could promote cartilage repair and ameliorate OA pathology in animal models, representing a novel therapeutic strategy. In this study, we demonstrated that extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUC-EVs) could maintain chondrocyte homeostasis and alleviate OA, and further revealed a novel molecular mechanism of this therapeutic effect. miR-223, which could directly bind with the 3'UTR of NLRP3 mRNA, was found to be a key miRNA for hUC-EVs to exert beneficial effects on inflammation inhibiting and cartilage protecting. For enhancing the effect on mitigating osteoarthritis, exogenous miR-223 was loaded into hUC-EVs by electroporation, and a collagen II-targeting peptide (WYRGRL) was modified onto the surface of hUC-EVs by genetic engineering to achieve a more targeted and efficient RNA delivery to the cartilage. The dual-engineered EVs showed a maximal effect on inhibiting the NLRP3 inflammasome activation and chondrocyte pyroptosis, and offered excellent results for the treatment of OA. This study provides a novel theoretical basis and a promising therapeutic strategy for the application of engineered extracellular vesicles in OA treatment.
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Affiliation(s)
- Weixuan Liu
- Department of Sports Medicine, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, China
- Shanghai Engineering Research Center for Orthopedic Material Innovation and Tissue Regeneration, Shanghai, 201306, China
| | - Anqi Liu
- Department of Orthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200001, China
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China
| | - Xujun Li
- Minhang Hospital, Fudan University, Shanghai, 201199, China
| | - Ziyang Sun
- Shanghai Engineering Research Center for Orthopedic Material Innovation and Tissue Regeneration, Shanghai, 201306, China
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Zhenghua Sun
- Shanghai Engineering Research Center for Orthopedic Material Innovation and Tissue Regeneration, Shanghai, 201306, China
| | - Yaru Liu
- Shanghai Engineering Research Center for Orthopedic Material Innovation and Tissue Regeneration, Shanghai, 201306, China
| | - Gang Wang
- Shanghai Engineering Research Center for Orthopedic Material Innovation and Tissue Regeneration, Shanghai, 201306, China
| | - Dan Huang
- Shanghai Engineering Research Center for Orthopedic Material Innovation and Tissue Regeneration, Shanghai, 201306, China
| | - Hao Xiong
- Shanghai Engineering Research Center for Orthopedic Material Innovation and Tissue Regeneration, Shanghai, 201306, China
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Shiyang Yu
- Shanghai Engineering Research Center for Orthopedic Material Innovation and Tissue Regeneration, Shanghai, 201306, China
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Xintao Zhang
- Department of Sports Medicine, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, China
| | - Cunyi Fan
- Shanghai Engineering Research Center for Orthopedic Material Innovation and Tissue Regeneration, Shanghai, 201306, China
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
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14
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Gan X, Zhou C, He P, Ye Z, Liu M, Yang S, Zhang Y, Zhang Y, Huang Y, Xiang H, Qin X. Inverse association of glucosamine use and risk of new-onset kidney stones in UK adults with less sedentary time. Prev Med 2023; 177:107738. [PMID: 37866696 DOI: 10.1016/j.ypmed.2023.107738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Revised: 10/15/2023] [Accepted: 10/17/2023] [Indexed: 10/24/2023]
Abstract
OBJECTIVE To assess the association of different sedentary behaviors and glucosamine use with the risk of kidney stones and examine the modification of genetic risk of kidney stones on this association. METHODS 473,225 participants free of kidney stones at baseline from the UK Biobank were included. Total sedentary time was calculated as the sum of the duration of TV-watching, driving, and non-occupational computer using. The primary outcome was new-onset kidney stones. RESULTS During a median follow-up of 12.0 years, 5528 cases of kidney stones were documented. All major sedentary behaviors and total sedentary time were significantly positively related to the risk of kidney stones (All P for trend<0.05). Participants with total sedentary time ≥ 3.5 h/day had a significantly higher risk of new-onset kidney stones (vs. <3.5 h/day [tertile 1]; HR, 1.18; 95%CI,1.10-1.27). Compared with non-users, participants who regularly used glucosamine had a significantly lower risk of new-onset kidney stones in those with total sedentary time < 3.5 h/day (HR, 0.72; 95%CI,0.59-0.86), but not in those with total sedentary time ≥ 3.5 h/day (HR, 0.99; 95%CI,0.91-1.08; P-interaction = 0.001). Among participants with total sedentary time < 3.5 h/day, there was a dose-response relationship of glucosamine use with new-onset kidney stones (P for trend<0.001). Genetic risks of kidney stones did not significantly modify the association. CONCLUSIONS TV-watching, driving and non-occupational computer using were all positively associated with the risk of new-onset kidney stones. Glucosamine use was associated with a lower risk of new-onset kidney stones in participants with total sedentary time < 3.5 h/day, following a dose-response relationship.
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Affiliation(s)
- Xiaoqin Gan
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510515, China
| | - Chun Zhou
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510515, China
| | - Panpan He
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510515, China
| | - Ziliang Ye
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510515, China
| | - Mengyi Liu
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510515, China
| | - Sisi Yang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510515, China
| | - Yanjun Zhang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510515, China
| | - Yuanyuan Zhang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510515, China
| | - Yu Huang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510515, China
| | - Hao Xiang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510515, China
| | - Xianhui Qin
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510515, China.
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15
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Cheleschi S, Veronese N, Carta S, Collodel G, Bottaro M, Moretti E, Corsaro R, Barbarino M, Fioravanti A. MicroRNA as Possible Mediators of the Synergistic Effect of Celecoxib and Glucosamine Sulfate in Human Osteoarthritic Chondrocyte Exposed to IL-1β. Int J Mol Sci 2023; 24:14994. [PMID: 37834442 PMCID: PMC10573984 DOI: 10.3390/ijms241914994] [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: 09/06/2023] [Revised: 10/02/2023] [Accepted: 10/05/2023] [Indexed: 10/15/2023] Open
Abstract
This study investigated the role of a pattern of microRNA (miRNA) as possible mediators of celecoxib and prescription-grade glucosamine sulfate (GS) effects in human osteoarthritis (OA) chondrocytes. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination, for 24 h, with or without interleukin (IL)-1β (10 ng/mL). Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis and reactive oxygen species (ROS) by cytometry, nitric oxide (NO) by Griess method. Gene levels of miRNA, antioxidant enzymes, nuclear factor erythroid (NRF)2, and B-cell lymphoma (BCL)2 expressions were analyzed by quantitative real time polymerase chain reaction (real time PCR). Protein expression of NRF2 and BCL2 was also detected at immunofluorescence and western blot. Celecoxib and GS, alone or in combination, significantly increased viability, reduced apoptosis, ROS and NO production and the gene expression of miR-34a, -146a, -181a, -210, in comparison to baseline and to IL-1β. The transfection with miRNA specific inhibitors significantly counteracted the IL-1β activity and potentiated the properties of celecoxib and GS on viability, apoptosis and oxidant system, through nuclear factor (NF)-κB regulation. The observed effects were enhanced when the drugs were tested in combination. Our data confirmed the synergistic anti-inflammatory and chondroprotective properties of celecoxib and GS, suggesting microRNA as possible mediators.
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Affiliation(s)
- Sara Cheleschi
- Rheumatology Unit, Department of Medicine, Surgery and Neuroscience, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, 53100 Siena, Italy;
| | - Nicola Veronese
- Geriatric Unit, Department of Internal Medicine and Geriatrics, University of Palermo, Viale Scaduto, 90100 Palermo, Italy
| | - Serafino Carta
- Section of Orthopedics and Traumatology, Department of Medicine, Surgery and Neurosciences, University of Siena, Policlinico Le Scotte, 53100 Siena, Italy;
| | - Giulia Collodel
- Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy; (G.C.); (E.M.); (R.C.)
| | - Maria Bottaro
- Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy; (M.B.); (M.B.)
- Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
| | - Elena Moretti
- Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy; (G.C.); (E.M.); (R.C.)
| | - Roberta Corsaro
- Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy; (G.C.); (E.M.); (R.C.)
| | - Marcella Barbarino
- Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy; (M.B.); (M.B.)
- Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
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Zhou C, Zhang Y, Yang S, Ye Z, Wu Q, Liu M, He P, Zhang Y, Qin X. Habitual glucosamine use, APOE genotypes, and risk of incident cause-specific dementia in the older population. Alzheimers Res Ther 2023; 15:152. [PMID: 37689747 PMCID: PMC10492372 DOI: 10.1186/s13195-023-01295-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 08/24/2023] [Indexed: 09/11/2023]
Abstract
BACKGROUND The relationship of glucosamine use with incident dementia in the older population remains uncertain. We aimed to evaluate the longitudinal association between habitual glucosamine supplement and the risk of cause-specific dementia and examine the possible effect modifiers on this association. METHODS The study included 214,945 participants over the age of 60 who had available information on glucosamine use and did not have dementia at baseline in the UK Biobank. The APOE genotypes were determined by a combination variant of rs429358 and rs7412. The primary outcome was incident vascular dementia, incident Alzheimer's disease, and incident frontotemporal dementia, respectively. RESULTS Over a median follow-up duration of 12 years, 1039, 1774, and 122 participants developed vascular dementia, Alzheimer's disease, and frontotemporal dementia, respectively. Overall, habitual glucosamine use was significantly associated with a lower risk of incident vascular dementia (adjusted HR, 0.82; 95%CI, 0.70-0.96), but not significantly associated with incident Alzheimer's disease (adjusted HR, 1.02; 95%CI, 0.92-1.14) and incident frontotemporal dementia (adjusted HR, 0.95; 95%CI, 0.63-1.43). Moreover, the inverse association between habitual glucosamine use and incident vascular dementia was more pronounced in participants with concomitant supplement of calcium (P-interaction = 0.011), and those without concomitant supplement of zinc (P-interaction = 0.018). However, APOE ε4 dosage and baseline cognitive function did not significantly modify the relationships of glucosamine use with incident vascular dementia or Alzheimer's disease (All P-interactions > 0.05). CONCLUSIONS Regardless of APOE genotypes and baseline cognitive function, habitual glucosamine use was significantly inversely associated with incident vascular dementia in the older population.
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Affiliation(s)
- Chun Zhou
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yanjun Zhang
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Sisi Yang
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Ziliang Ye
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Qimeng Wu
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Mengyi Liu
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Panpan He
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yuanyuan Zhang
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Xianhui Qin
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
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Bhimani J, O'Connell K, Kuk D, Du M, Navarro SL, Kantor ED. Glucosamine and Chondroitin Use and Mortality Among Adults in the United States from 1999 to 2014. JOURNAL OF INTEGRATIVE AND COMPLEMENTARY MEDICINE 2023; 29:492-500. [PMID: 36971848 PMCID: PMC10457612 DOI: 10.1089/jicm.2022.0783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Introduction: Glucosamine and chondroitin are supplements that are often, but not always, used in combination for arthritis and joint pain. Multiple studies have suggested that glucosamine and chondroitin may be associated with reduced risk of several diseases, as well as all-cause, cancer- and respiratory disease-specific mortality. Methods: Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) were used to further evaluate the association between glucosamine and chondroitin with mortality. Participants include 38,021 adults, ages 20+ years and older, who completed the detailed NHANES between 1999 and 2014. Participants were followed for death through linkage with the National Death Index through the end of 2015, over which time 4905 deaths occurred. Adjusted hazard ratios (HRs) for overall and cause-specific mortality were estimated using Cox regression models. Results: Despite glucosamine and chondroitin use appearing to be inversely associated with mortality in the minimally adjusted models, no association was observed in multivariable models (glucosamine: HR = 1.02; 95% confidence interval [CI]: 0.86-1.21, chondroitin: HR = 1.04, 95% CI: 0.87-1.25). No association with cancer mortality or other mortality rate was observed after multivariable adjustment. There was a suggestive, nonsignificant inverse association for cardiovascular-specific mortality (glucosamine HR = 0.72; 95% CI: 0.46-1.15, chondroitin: HR = 0.76; 95% CI: 0.47-1.21). Conclusion: The lack of significant relationship between glucosamine and chondroitin use and all-cause or cause-specific mortality after adjusting extensively for multiple covariates in this nationally representative adult population was in contrast to prior literature. Given the limited power to explore the cause-specific mortality, future well-powered studies will be needed to better understand the potential association with cardiovascular-specific mortality.
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Affiliation(s)
- Jenna Bhimani
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kelli O'Connell
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Deborah Kuk
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Inspire, Arlington, VA, USA
| | - Mengmeng Du
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Sandi L. Navarro
- Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Elizabeth D. Kantor
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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18
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Le Q, Zhang Z, Sun D, Cui Q, Yang X, Hassan AE. Anti-inflammatory activities of two new deoxygenated N-acetyl glucosamines in lipopolysaccharide-activated mouse macrophage RAW264.7 cells. Heliyon 2023; 9:e15769. [PMID: 37159698 PMCID: PMC10163627 DOI: 10.1016/j.heliyon.2023.e15769] [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: 09/08/2022] [Revised: 04/18/2023] [Accepted: 04/20/2023] [Indexed: 05/11/2023] Open
Abstract
Background Glucosamine and N-acetyl-glucosamine (NAG) are amino sugars found in human extracellular matrix with previously described anti-inflammatory effects. Despite mixed results from clinical studies, these molecules have been used extensively in supplements. Objective We investigated the anti-inflammatory properties of two synthesized derivatives of N-acetyl-glucosamine (NAG), bi-deoxy-N-acetyl-glucosamine (BNAG) 1 and 2. Methods Using mouse macrophage RAW 264.7 cells with lipopolysaccharide (LPS) to induce inflammation, the effects of NAG, BNAG 1, and BNAG 2 on the expression of IL-6, IL-1β, inducible nitric oxide synthase (iNOS) and COX-2 were studied using ELISA, Western blot and quantitative RT-PCR. Cell toxicity and nitric oxide (NO) production were evaluated using WST-1 assay and the Griess reagent, respectively. Results Among the three tested compounds, BNAG1 shows the highest inhibition of iNOS, IL-6, TNF α and IL-1β expression and NO production. All three tested compounds show slight inhibition on cell proliferation of RAW 264.7 cells, except that BNAG1 displays a remarkable toxicity at the tested maximum dose of 5 mM. Conclusion BNAG 1 and 2 exhibit notable anti-inflammatory effects compared to the parent NAG molecule.
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Affiliation(s)
- Quang Le
- Dept of Orthopaedic Surgery, University of Virginia, 22903, USA
| | - Zhichang Zhang
- Dept of Orthopaedic Surgery, University of Virginia, 22903, USA
- Dept of Orthopaedic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Wehui, 453100, Henan, China
| | - Daniel Sun
- Dept of Orthopaedic Surgery, University of Virginia, 22903, USA
| | - Quanjun Cui
- Dept of Orthopaedic Surgery, University of Virginia, 22903, USA
| | - Xinlin Yang
- Dept of Orthopaedic Surgery, University of Virginia, 22903, USA
- Corresponding author. Department of Orthopaedic Surgery, University of Virginia, School of Medicine, 450 Ray C. Hunt Drive, Charlottesville, VA 22908, USA.
| | - Ameer E. Hassan
- Department of Neuroscience, Valley Baptist Medical Center, 78550, USA
- Corresponding author. Department of Neuroscience, Valley Baptist Medical Center, 2101 Pease St, Harlingen, TX, 78550, USA.
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19
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Liu B, Yang W, Zhang K. Role of Glucosamine and Chondroitin in the Prevention of Cancer: A Meta-Analysis. Nutr Cancer 2023; 75:785-794. [PMID: 36715012 DOI: 10.1080/01635581.2023.2173258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The anti-inflammatory properties of glucosamine and chondroitin suggest that they may have potential effects in cancer prevention. We performed this meta-analysis to assess the protective function of glucosamine and/or chondroitin intake against cancer risk. We searched the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) databases. The odds ratio (OR), corresponding to the 95% confidence interval (95% CI), was used to assess the association between chondroitin and/or glucosamine intake and cancer risk. Thirteen studies met the inclusion criteria, with 1,690,918 participants and 55,045 cancer cases. Overall, chondroitin and/or glucosamine intake was associated with a lower risk of colorectal cancer (OR = 0.91, 95% CI, 0.87-0.94) and lung cancer (OR = 0.84, 95% CI, 0.79-0.89). Subgroup analysis supported the protective effect of different SYSADOAs (chondroitin and/or glucosamine) intake. However, the protective effect was not observed in the only chondroitin intake group and in the NSAIDs group. Our meta-analysis found that the intake of glucosamine and/or chondroitin decreased the risk of colorectal and lung cancers. Moreover, NSAIDs use may have a synergistic protective effect.
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Affiliation(s)
- Bo Liu
- Department of Forensic Pathology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Wenxing Yang
- Department of Physiology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Kui Zhang
- Department of Forensic Pathology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China
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20
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Gromova OA, Torshin IY, Lila AM. On the use of chondroitin sulfate, glucosamine sulfate and undenatured type II collagen for back and limb pain and osteoarthritis. NEUROLOGY, NEUROPSYCHIATRY, PSYCHOSOMATICS 2022. [DOI: 10.14412/2074-2711-2022-6-122-130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- O. A. Gromova
- Institute of Pharmacoinformatics of the Federal Research Center “Computer Science and Management”, Russian Academy of Sciences
| | - I. Y. Torshin
- Institute of Pharmacoinformatics of the Federal Research Center “Computer Science and Management”, Russian Academy of Sciences
| | - A. M. Lila
- V.A. Nasonova Research Institute of Rheumatology; Department of Rheumatology, Russian Medical Academy of Continuing Professional Education
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21
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Fahie KMM, Papanicolaou KN, Zachara NE. Integration of O-GlcNAc into Stress Response Pathways. Cells 2022; 11:3509. [PMID: 36359905 PMCID: PMC9654274 DOI: 10.3390/cells11213509] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/31/2022] [Accepted: 11/02/2022] [Indexed: 11/09/2022] Open
Abstract
The modification of nuclear, mitochondrial, and cytosolic proteins by O-linked βN-acetylglucosamine (O-GlcNAc) has emerged as a dynamic and essential post-translational modification of mammalian proteins. O-GlcNAc is cycled on and off over 5000 proteins in response to diverse stimuli impacting protein function and, in turn, epigenetics and transcription, translation and proteostasis, metabolism, cell structure, and signal transduction. Environmental and physiological injury lead to complex changes in O-GlcNAcylation that impact cell and tissue survival in models of heat shock, osmotic stress, oxidative stress, and hypoxia/reoxygenation injury, as well as ischemic reperfusion injury. Numerous mechanisms that appear to underpin O-GlcNAc-mediated survival include changes in chaperone levels, impacts on the unfolded protein response and integrated stress response, improvements in mitochondrial function, and reduced protein aggregation. Here, we discuss the points at which O-GlcNAc is integrated into the cellular stress response, focusing on the roles it plays in the cardiovascular system and in neurodegeneration.
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Affiliation(s)
- Kamau M. M. Fahie
- Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Kyriakos N. Papanicolaou
- Department of Medicine, Division of Cardiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Natasha E. Zachara
- Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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22
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Antinociceptive effect of N-acetyl glucosamine in a rat model of neuropathic pain. Acta Neuropsychiatr 2022; 34:260-268. [PMID: 35109948 DOI: 10.1017/neu.2022.3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
OBJECTIVE This study was aimed at evaluating the efficacy of glucosamine and potential mechanisms of actions in a neuropathic pain model in rats. METHODS Glucosamine (500, 1000 and 2000 mg/kg) was administered via gavage route, 1 day before the chronic constriction injury (CCI) of sciatic nerve and daily for 14 days (prophylactic regimen), or from days 5 to 14 post-injury (therapeutic regimen), as the indicators of neuropathic pain, mechanical allodynia, cold allodynia and thermal hyperalgesia were assessed on days 0, 3, 5, 7, 10 and 14 after ligation. Inducible nitric oxide synthase (iNOS) and tumour necrosis factor alpha (TNF-α) gene expressions were measured by real-time polymerase chain reaction. TNF-α protein content was measured using the enzyme-linked immunosorbent assay method. RESULTS Three days after nerve injury, the threshold of pain was declined among animals subjected to neuropathic pain. Mechanical and cold allodynia, as well as thermal hyperalgesia were attenuated by glucosamine (500, 1000, 2000 mg/kg) in the prophylactic regimen. However, existing pain was not decreased by this drug. Increased mRNA expression of iNOS and TNF-α was significantly reduced in the spinal cord of CCI animals by glucosamine (500, 1000, 2000 mg/kg) in the prophylactic regimen. The overall expression of spinal TNF-α was increased by CCI, but this increase was reduced in animals receiving glucosamine prophylactic treatment. CONCLUSION Findings suggest that glucosamine as a safe supplement may be a useful candidate in preventing neuropathic pain following nerve injury. Antioxidant and anti-inflammatory effects may be at least in part responsible for the antinociceptive effects of this drug.
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23
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Spahr A, Divnic‐Resnik T. Impact of health and lifestyle food supplements on periodontal tissues and health. Periodontol 2000 2022; 90:146-175. [PMID: 35916868 PMCID: PMC9804634 DOI: 10.1111/prd.12455] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
According to the new classification, periodontitis is defined as a chronic multifactorial inflammatory disease associated with dysbiotic biofilms and characterized by progressive destruction of the tooth-supporting apparatus. This definition, based on the current scientific evidence, clearly indicates and emphasizes, beside the microbial component dental biofilm, the importance of the inflammatory reaction in the progressive destruction of periodontal tissues. The idea to modulate this inflammatory reaction in order to decrease or even cease the progressive destruction was, therefore, a logical consequence. Attempts to achieve this goal involve various kinds of anti-inflammatory drugs or medications. However, there is also an increasing effort in using food supplements or so-called natural food ingredients to modulate patients' immune responses and maybe even improve the healing of periodontal tissues. The aim of this chapter of Periodontology 2000 is to review the evidence of various food supplements and ingredients regarding their possible effects on periodontal inflammation and wound healing. This review may help researchers and clinicians to evaluate the current evidence and to stimulate further research in this area.
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Affiliation(s)
- Axel Spahr
- Discipline of Periodontics, School of Dentistry, Faculty of Medicine and HealthThe University of SydneySydneyNew South WalesAustralia
| | - Tihana Divnic‐Resnik
- Discipline of Periodontics, School of Dentistry, Faculty of Medicine and HealthThe University of SydneySydneyNew South WalesAustralia
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24
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Liu M, Ye Z, Zhang Y, Yang S, Wu Q, Zhou C, He P, Zhang Y, Gan X, Qin X. Associations of habitual glucosamine supplementation with incident gout: a large population based cohort study. Biol Sex Differ 2022; 13:52. [PMID: 36175979 PMCID: PMC9524004 DOI: 10.1186/s13293-022-00461-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 09/20/2022] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVES The association between habitual glucosamine use and incident gout has not been examined in previous studies. We aimed to evaluate the association of habitual use of glucosamine with the risk of gout in general population. METHODS A total of 436,594 participants (55.4% female) without prior gout at baseline who completed a questionnaire on supplementation use, which included glucosamine, in the UK Biobank were enrolled. Incident gout was recorded from self-report, death register, primary care, and hospital admission data. RESULTS At baseline, 53,433 (22.1%) females and 30,685 (15.8%) males reported habitual glucosamine use. During a median follow-up period of 12.1 years, 1718 (0.7%) females and 5685 (2.9%) males developed gout. After multivariable adjustment for major risk factors, glucosamine use was associated with a significantly lower risk of incident gout in females (hazard ratio [HR], 0.81, 95% confidence interval [CI], 0.71-0.92), but not in males (HR, 1.05, 95% CI, 0.97-1.13), compared with non-use (P-interaction < 0.001). Among females, the inverse association between glucosamine use and gout was stronger in participants with diuretics use (HR, 0.64, 95% CI, 0.50-0.81) than those without diuretics use (HR, 0.89, 95% CI, 0.77-1.03) (P-interaction = 0.015). Moreover, gout genetic risk scores did not significantly modify the association between glucosamine use and the risk of incident gout in males (P-interaction = 0.548) or females (P-interaction = 0.183). CONCLUSIONS Habitual glucosamine use to relieve osteoarthritis pain was related to lower risk of gout in females, but not in males.
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Affiliation(s)
- Mengyi Liu
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, 510515, China
| | - Ziliang Ye
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, 510515, China
| | - Yanjun Zhang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, 510515, China
| | - Sisi Yang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, 510515, China
| | - Qimeng Wu
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, 510515, China
| | - Chun Zhou
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, 510515, China
| | - Panpan He
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, 510515, China
| | - Yuanyuan Zhang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, 510515, China
| | - Xiaoqin Gan
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, 510515, China
| | - Xianhui Qin
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, 510515, China.
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25
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Yeshi K, Ruscher R, Loukas A, Wangchuk P. Immunomodulatory and biological properties of helminth-derived small molecules: Potential applications in diagnostics and therapeutics. FRONTIERS IN PARASITOLOGY 2022; 1:984152. [PMID: 39816468 PMCID: PMC11731824 DOI: 10.3389/fpara.2022.984152] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 08/23/2022] [Indexed: 01/18/2025]
Abstract
Parasitic helminths secrete and excrete a vast array of molecules known to help skew or suppress the host's immune response, thereby establishing a niche for sustained parasite maintenance. Indeed, the immunomodulatory potency of helminths is attributed mainly to excretory/secretory products (ESPs). The ESPs of helminths and the identified small molecules (SM) are reported to have diverse biological and pharmacological properties. The available literature reports only limited metabolites, and the identity of many metabolites remains unknown due to limitations in the identification protocols and helminth-specific compound libraries. Many metabolites are known to be involved in host-parasite interactions and pathogenicity. For example, fatty acids (e.g., stearic acid) detected in the infective stages of helminths are known to have a role in host interaction through facilitating successful penetration and migration inside the host. Moreover, excreted/secreted SM detected in helminth species are found to possess various biological properties, including anti-inflammatory activities, suggesting their potential in developing immunomodulatory drugs. For example, helminths-derived somatic tissue extracts and whole crude ESPs showed anti-inflammatory properties by inhibiting the secretion of proinflammatory cytokines from human peripheral blood mononuclear cells and suppressing the pathology in chemically-induced experimental mice model of colitis. Unlike bigger molecules like proteins, SM are ideal candidates for drug development since they are small structures, malleable, and lack immunogenicity. Future studies should strive toward identifying unknown SM and isolating the under-explored niche of helminth metabolites using the latest metabolomics technologies and associated software, which hold potential keys for finding new diagnostics and novel therapeutics.
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Affiliation(s)
- Karma Yeshi
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine (AITHM), James Cook University, Cairns, QLD, Australia
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26
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A 2022 Systematic Review and Meta-Analysis of Enriched Therapeutic Diets and Nutraceuticals in Canine and Feline Osteoarthritis. Int J Mol Sci 2022; 23:ijms231810384. [PMID: 36142319 PMCID: PMC9499673 DOI: 10.3390/ijms231810384] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 09/04/2022] [Accepted: 09/04/2022] [Indexed: 11/17/2022] Open
Abstract
With osteoarthritis being the most common degenerative disease in pet animals, a very broad panel of natural health products is available on the market for its management. The aim of this systematic review and meta-analysis, registered on PROSPERO (CRD42021279368), was to test for the evidence of clinical analgesia efficacy of fortified foods and nutraceuticals administered in dogs and cats affected by osteoarthritis. In four electronic bibliographic databases, 1578 publications were retrieved plus 20 additional publications from internal sources. Fifty-seven articles were included, comprising 72 trials divided into nine different categories of natural health compound. The efficacy assessment, associated to the level of quality of each trial, presented an evident clinical analgesic efficacy for omega-3-enriched diets, omega-3 supplements and cannabidiol (to a lesser degree). Our analyses showed a weak efficacy of collagen and a very marked non-effect of chondroitin-glucosamine nutraceuticals, which leads us to recommend that the latter products should no longer be recommended for pain management in canine and feline osteoarthritis.
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Glucosamine use, smoking and risk of incident chronic obstructive pulmonary disease: a large prospective cohort study. Br J Nutr 2022; 128:721-732. [PMID: 34526168 PMCID: PMC9892851 DOI: 10.1017/s000711452100372x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40-69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29-9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.
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28
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Xiong H, Zhao Y, Xu Q, Xie X, Wu J, Hu B, Chen S, Cai X, Zheng Y, Fan C. Biodegradable Hollow-Structured Nanozymes Modulate Phenotypic Polarization of Macrophages and Relieve Hypoxia for Treatment of Osteoarthritis. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2203240. [PMID: 35843877 DOI: 10.1002/smll.202203240] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 06/24/2022] [Indexed: 06/15/2023]
Abstract
Nanozymes are widely applied for treating various major diseases, including neurological diseases and tumors. However, the biodegradability of nanozymes remains a great challenge, which hinders their further clinical translation. Based on the microenvironment of osteoarthritis (OA), a representative pH-responsive biodegradable hollow-structured manganese Prussian blue nanozyme (HMPBzyme) is designed and applied for treatment of OA. HMPBzyme with good pH-responsive biodegradability, biocompatibility, and multi-enzyme activities is constructed by bovine serum albumin bubbles as a template-mediated biomineralization strategy. HMPBzyme suppresses hypoxia-inducible factor-1α (HIF-1α) expression and decreases reactive oxygen species (ROS) level in the in vitro experiment. Furthermore, HMPBzyme markedly suppresses the expression of ROS and alleviates the degeneration of cartilage in OA rat models. The results indicate that the biodegradable HMPBzyme inhibits oxidative damage and relieves hypoxia synergistically to suppress inflammation and promote the anabolism of cartilage extracellular matrix by protecting mitochondrial function and down-regulating the expression of HIF-1α, which modulates the phenotypic conversion of macrophages from pro-inflammatory M1 subtype to anti-inflammatory M2 subtype for OA treatment. This research lays a solid foundation for the design, construction, and biomedical application of biodegradable nanozymes and promotes the application of nanozymes in biomedicine.
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Affiliation(s)
- Hao Xiong
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Building 3, Langu Science and Technology Park, Lane 70, Haiji 6th Road, Shanghai, 201306, China
| | - Yongzheng Zhao
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Qinyuan Xu
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Xue Xie
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Jianrong Wu
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Bing Hu
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Shuai Chen
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Building 3, Langu Science and Technology Park, Lane 70, Haiji 6th Road, Shanghai, 201306, China
| | - Xiaojun Cai
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Yuanyi Zheng
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Cunyi Fan
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Building 3, Langu Science and Technology Park, Lane 70, Haiji 6th Road, Shanghai, 201306, China
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Non-surgical therapy for the treatment of chronic low back pain in patients with Modic changes: A systematic review of the literature. Heliyon 2022; 8:e09658. [PMID: 35800246 PMCID: PMC9253919 DOI: 10.1016/j.heliyon.2022.e09658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 04/13/2022] [Accepted: 05/31/2022] [Indexed: 11/23/2022] Open
Abstract
Background In absence of uniform therapeutic recommendations, knowledge of the available treatment options for Modic changes (MCs) patients and their safety and effectiveness would be crucial and significant for clinicians and such patients. Objectives The aim of this study was to provide a systematic review of available studies on non-surgical treatments of MCs. Methods We performed a systematic review of multiple electronic databases including PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure for the period until 31st August 2021 to search for studies on non-surgical treatments for MCs in accordance with the guidance of the Cochrane Handbook. Potential studies were screened by their titles and abstracts. The methodological quality of the included studies was independently evaluated by two authors. Final recommendations for the included interventions were developed based on grades of recommendations. The narrative format was adopted to synthesize the findings of the present work. Results Fifth studies involving a total of 1147 patients were identified for this systematic review. The results of this review demonstrated that spinal manipulation has been suggested as an alternative option for patients with MCs. However, there was insufficient evidence to support that patients with MCs can benefit from the medication and wearing the rigid lumbar brace. Moreover, the rationale and safety for the use of antibiotics in such patients remain highly controversial. Low evidence revealed that exercise therapy might decrease pain intensity only for special subgroups of MCs patients. Conclusions There is not yet enough evidence to suggest that non-surgical treatments are useful for patients with MCs. Further high-quality, multicenter trials are required to validate the effectiveness of these non-surgical treatments.
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Gratal P, Mediero A, Lamuedra A, Matamoros-Recio A, Herencia C, Herrero-Beaumont G, Martín-Santamaría S, Largo R. 6-shogaol treatment improves experimental knee OA exerting a pleiotropic effect over immune innate signaling response in chondrocytes. Br J Pharmacol 2022; 179:5089-5108. [PMID: 35760458 DOI: 10.1111/bph.15908] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 04/09/2022] [Accepted: 06/14/2022] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND AND PURPOSE The pathogenesis of osteoarthritis (OA) implicates a low-grade inflammation associated to the activation of the innate immune system. Toll like receptor (TLR) stimulation triggers the release of inflammatory mediators, which aggravate OA severity. The aim was to study the preventive effect of 6-shogaol (6S), a potential TLR4 inhibitor, on the treatment of experimental knee OA. EXPERIMENTAL APPROACH OA was induced in C57BL6 mice by surgical section of the medial meniscotibial ligament, which received 6S for eight weeks. Cartilage damage, inflammatory mediator presence, and disease markers were assessed in the joint tissues by immunohistochemistry. Computational modelling was used to predict binding modes of 6S into the TLR4/MD2 receptor and its permeability across cellular membranes. Employing LPS-stimulated chondrocytes and MAPK assay, we clarified 6S action mechanisms. KEY RESULTS 6S treatment was able to prevent articular cartilage lesions, synovitis, and the presence of pro-inflammatory mediators and disease markers in OA animals. Molecular modelling studies predicted 6S interaction with the TLR4/MD-2 heterodimer in an antagonist conformation through its binding into the MD-2 pocket. In cell culture, we confirmed that 6S reduced LPS-induced TLR4 inflammatory signaling pathways. Besides, MAPK assay demonstrated that 6S directly inhibits the ERK1/2 phosphorylation activity. CONCLUSION AND IMPLICATIONS 6S evoked a preventive action on cartilage and synovial inflammation in OA mice. 6S effect may take place not only by hindering the interaction between TLR4 ligands and the TLR4/MD-2 complex in chondrocytes, but also through inhibition of ERK phosphorylation, implying a pleiotropic effect on different mediators activated during OA, which proposes it as an attractive drug for OA treatment.
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Affiliation(s)
- Paula Gratal
- Bone and Joint Research Unit, Service of Rheumatology, IIS-Fundación Jiménez Díaz, Autonomous University of Madrid, Madrid, Spain
| | - Aránzazu Mediero
- Bone and Joint Research Unit, Service of Rheumatology, IIS-Fundación Jiménez Díaz, Autonomous University of Madrid, Madrid, Spain
| | - Ana Lamuedra
- Bone and Joint Research Unit, Service of Rheumatology, IIS-Fundación Jiménez Díaz, Autonomous University of Madrid, Madrid, Spain
| | - Alejandra Matamoros-Recio
- Department of Structural and Chemical Biology, Centro de Investigaciones Biológicas Margarita Salas, CIB-CSIC, Madrid, Spain
| | - Carmen Herencia
- Bone and Joint Research Unit, Service of Rheumatology, IIS-Fundación Jiménez Díaz, Autonomous University of Madrid, Madrid, Spain
| | - Gabriel Herrero-Beaumont
- Bone and Joint Research Unit, Service of Rheumatology, IIS-Fundación Jiménez Díaz, Autonomous University of Madrid, Madrid, Spain
| | - Sonsoles Martín-Santamaría
- Department of Structural and Chemical Biology, Centro de Investigaciones Biológicas Margarita Salas, CIB-CSIC, Madrid, Spain
| | - Raquel Largo
- Bone and Joint Research Unit, Service of Rheumatology, IIS-Fundación Jiménez Díaz, Autonomous University of Madrid, Madrid, Spain
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Afolabi OA, Anyogu DC, Hamed MA, Odetayo AF, Adeyemi DH, Akhigbe RE. Glutamine prevents upregulation of NF-kB signaling and caspase 3 activation in ischaemia/reperfusion-induced testicular damage: An animal model. Biomed Pharmacother 2022; 150:113056. [PMID: 35658227 DOI: 10.1016/j.biopha.2022.113056] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 04/26/2022] [Accepted: 04/26/2022] [Indexed: 11/02/2022] Open
Abstract
AIM Testicular ischaemia/reperfusion (I/R) injury is a major consequence of testicular torsion with possible attendant risk of male infertility. Glutamine, on the other hand, is a known antioxidant with anti-inflammatory potential. The present study evaluated whether or not glutamine would improve I/R-induced testicular injury in torsion/detorsion (T/D). The possible associated mechanisms were also investigated. METHODS Wistar rats were randomly allotted into four groups (n = 10); sham-operated, glutamine-treated, T/D, and T/D + glutamine. Testicular torsion was induced and reperfusion established after two and a half hour under ketamine/xylazine anaethesia. Glutamine was administered one hour before reperfusion and continued daily for 3 days. At the end of the study, animals were euthanized, blood samples obtained, epididymal sperm suspension collected, and the testes harvested for biochemical and histopathological assays using established methods. RESULTS Glutamine prevented T/D-driven I/R-induced reduced sperm quality, impaired testicular histoarchitecture, and suppressed circulating testosterone. Also, glutamine abated I/R-induced oxidative stress (evidenced by reduced hydrogen peroxide and MDA generation and enhanced concentrations and activities of antioxidants), inflammation (evidenced by suppression of TNF-α and IL-1β), and apoptosis (evidenced by reduced DNA fragmentation) by down-regulating NF-kB and caspase 3 activity. CONCLUSION For the first time, this study demonstrated that glutamine administration improved testicular I/R injury in T/D rat model by maintaining testicular redox balance, and testicular integrity and function via inhibition of I/R-induced upregulation of NF-kB signaling and caspase 3 activation.
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Affiliation(s)
- O A Afolabi
- Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
| | - D C Anyogu
- Department of Veterinary Pathology and Microbiology, University of Nigeria, Nsukka, Nigeria
| | - M A Hamed
- Brainwill Laboratories, Osogbo, Osun State, Nigeria; Reproductive Biology and Toxicology Research Laboratory, Oasis of Grace Hospital, Osogbo, Osun State, Nigeria
| | - A F Odetayo
- Reproductive Biology and Toxicology Research Laboratory, Oasis of Grace Hospital, Osogbo, Osun State, Nigeria; Department of Physiology, University of Ilorin, Ilorin, Kwara State, Nigeria
| | - D H Adeyemi
- Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, University, Osun State, Nigeria
| | - R E Akhigbe
- Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria; Reproductive Biology and Toxicology Research Laboratory, Oasis of Grace Hospital, Osogbo, Osun State, Nigeria.
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Tenti S, Veronese N, Cheleschi S, Seccafico I, Bruyère O, Reginster JY, Fioravanti A. Prescription-grade crystalline glucosamine sulfate as an add-on therapy to conventional treatments in erosive osteoarthritis of the hand: results from a 6-month observational retrospective study. Aging Clin Exp Res 2022; 34:1613-1625. [PMID: 35637324 PMCID: PMC9246990 DOI: 10.1007/s40520-022-02151-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 05/02/2022] [Indexed: 11/26/2022]
Abstract
Objective To evaluate the efficacy of prescription-grade Crystalline Glucosamine Sulfate (pCGS) as an add-on treatment to conventional therapy, compared to usual therapy alone, in patients with erosive osteoarthritis of the hand (EHOA). Methods This 6-month retrospective case–control study included patients with concomitant knee osteoarthritis and symptomatic EHOA. Participants were stratified into two groups based on whether or not pCGS (1500 mg/day) was added to the conventional therapy (education and training in ergonomic principles, exercise and use on-demand of symptomatic drugs) for hand osteoarthritis. Patients were evaluated at baseline, after 3 and 6 months. Primary outcomes were the change from baseline to month 6 in Visual Analogue Scale (VAS) hand pain and in Functional Index for Hand Osteoarthritis (FIHOA) score. A set of secondary parameters was also evaluated. Results 123 patients were included as follows: 67 treated with pCGS in addition to conventional therapy (pCGS Group) and 56 with conventional therapy alone (Control Group). After 6 months a significant difference in VAS and in FIHOA score (p < 0.01 and p < 0.001, respectively) was observed in favor of pCGS Group. Similar results were found for morning stiffness duration (p < 0.05), health assessment questionnaire (p < 0.01) and physical and mental component score of 36-item short form (p < 0.05 and p < 0.001, respectively). A significant reduction of symptomatic drug consumption at 3 and 6 months was reported in the pCGS Group (p < 0.001). No serious adverse event was recorded in both groups. Conclusions Despite all the limitations inherent to an observational study, our results suggest the potential effectiveness of pCGS, when used in combination with conventional therapy in EHOA. Further randomized placebo-controlled trials are needed to confirm these positive findings. Trial Registration ClinicalTrials.gov, http://www.clinicaltrials.gov, date of registration: February
2, 2022, NCT05237596. The present trial was retrospectively registered. Supplementary Information The online version contains supplementary material available at 10.1007/s40520-022-02151-7.
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Affiliation(s)
- Sara Tenti
- Clinic for the Diagnosis and Management of Hand Osteoarthritis, Rheumatology Unit, Department of Medicine, Surgery and Neuroscience, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Viale Bracci 1, 53100, Siena, Italy
| | - Nicola Veronese
- Geriatric Unit, Department of Internal Medicine and Geriatrics, University of Palermo, Palermo, Italy
| | - Sara Cheleschi
- Clinic for the Diagnosis and Management of Hand Osteoarthritis, Rheumatology Unit, Department of Medicine, Surgery and Neuroscience, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Viale Bracci 1, 53100, Siena, Italy
| | - Iole Seccafico
- Clinic for the Diagnosis and Management of Hand Osteoarthritis, Rheumatology Unit, Department of Medicine, Surgery and Neuroscience, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Viale Bracci 1, 53100, Siena, Italy
| | - Olivier Bruyère
- Division of Public Health, Epidemiology and Health, Economics, WHO Collaborating Centre for Public Health, Aspects of Musculo-Skeletal Health and Ageing, University of Liege, Liege, Belgium
| | - Jean-Yves Reginster
- Division of Public Health, Epidemiology and Health, Economics, WHO Collaborating Centre for Public Health, Aspects of Musculo-Skeletal Health and Ageing, University of Liege, Liege, Belgium
| | - Antonella Fioravanti
- Clinic for the Diagnosis and Management of Hand Osteoarthritis, Rheumatology Unit, Department of Medicine, Surgery and Neuroscience, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Viale Bracci 1, 53100, Siena, Italy.
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Hamed MA, Akhigbe TM, Akhigbe RE, Aremu AO, Oyedokun PA, Gbadamosi JA, Anifowose PE, Adewole MA, Aboyeji OO, Yisau HO, Tajudeen GO, Titiloye MM, Ayinla NF, Ajayi AF. Glutamine restores testicular glutathione-dependent antioxidant defense and upregulates NO/cGMP signaling in sleep deprivation-induced reproductive dysfunction in rats. Biomed Pharmacother 2022; 148:112765. [PMID: 35247715 DOI: 10.1016/j.biopha.2022.112765] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 02/19/2022] [Accepted: 02/27/2022] [Indexed: 12/14/2022] Open
Abstract
Oxidative stress has been linked with sleep deprivation (SD)-induced pathological conditions and reproductive dysfunction. On the other hand, glutamine has been established to have antioxidant property. However, the impact of SD, with or without glutamine, on male reproductive function is yet to be elucidated. Thus, this study was designed to investigate the role of SD, with or without glutamine, on male reproductive function and possible associated mechanisms. Ten-week old male Wistar rats weighing 175.6 g± 0.42 were randomly assigned into vehicle that received per os (p.o.) distilled water, glutamine (1 g/kg; po), SD, and SD + glutamine that received treatments as glutamine and SD. Treatment/exposure lasted for 72 h. The results showed that SD led to reduced body weight, seminiferous luminal and epididymal sperm density, low sperm quality, increased testicular and epididymal malondialdehyde, uric acid, DNA fragmentation, and testicular injury markers. In addition, SD caused a reduction in reduced glutathione level and activities of superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione-S-transferase. Also, SD increased tumor necrotic factor-α, interleukin-1β, and nuclear factor-kappa B levels. Furthermore SD led to impaired libido and erectile dysfunction, and suppression of circulatory nitric oxide, gonadotropins and testosterone, and penile cGMP. However, glutamine attenuated the effects induced by SD. Taken together, the findings of this study demonstrate that SD induces reproductive dysfunction via glutathione-dependent defense depletion and down-regulation of NO/cGMP signaling, which was abolished by glutamine supplementation.
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Affiliation(s)
- M A Hamed
- Brainwill Laboratories and Biomedical Services, Osogbo, Osun State, Nigeria; Reproductive Biology and Toxicology Research Laboratories, Oasis of Grace Hospital, Osogbo, Osun State, Nigeria
| | - T M Akhigbe
- Reproductive Biology and Toxicology Research Laboratories, Oasis of Grace Hospital, Osogbo, Osun State, Nigeria; Department of Agronomy, Osun State University, Osun State, Nigeria
| | - R E Akhigbe
- Reproductive Biology and Toxicology Research Laboratories, Oasis of Grace Hospital, Osogbo, Osun State, Nigeria; Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.
| | - A O Aremu
- Reproductive Biology and Toxicology Research Laboratories, Oasis of Grace Hospital, Osogbo, Osun State, Nigeria; Department of Morbid Anatomy, Obafemi Awolowo University Teaching Hospital Complex (OAUTHC), Ile-Ife, Osun State, Nigeria
| | - P A Oyedokun
- Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
| | - J A Gbadamosi
- Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
| | - P E Anifowose
- Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
| | - M A Adewole
- Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
| | - O O Aboyeji
- Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
| | - H O Yisau
- Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
| | - G O Tajudeen
- Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
| | - M M Titiloye
- Igbinedion University, Okada, Edo State, Nigeria
| | - N F Ayinla
- Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
| | - A F Ajayi
- Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria; Department of Morbid Anatomy, Obafemi Awolowo University Teaching Hospital Complex (OAUTHC), Ile-Ife, Osun State, Nigeria
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Amiri F, Babaei M, Jamshidi N, Agheb M, Rafienia M, Kazemi M. Fabrication and assessment of a novel hybrid scaffold consisted of polyurethane-gellan gum-hyaluronic acid-glucosamine for meniscus tissue engineering. Int J Biol Macromol 2022; 203:610-622. [PMID: 35051502 DOI: 10.1016/j.ijbiomac.2022.01.091] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 01/10/2022] [Accepted: 01/12/2022] [Indexed: 02/08/2023]
Abstract
The meniscus has inadequate intrinsic regenerative capacity and its damage can lead to degeneration of articular cartilage. Meniscus tissue engineering aims to restore an injured meniscus followed by returning its normal function through bioengineered scaffolds. In the present study, the structural and biological properties of 3D-printed polyurethane (PU) scaffolds dip-coated with gellan gum (GG), hyaluronic acid (HA), and glucosamine (GA) were investigated. The optimum concentration of GG was 3% (w/v) with maintaining porosity at 88.1%. The surface coating of GG-HA-GA onto the PU scaffolds increased the compression modulus from 30.30 kPa to 59.10 kPa, the water uptake ratio from 27.33% to 60.80%, degradation rate from 5.18% to 8.84%, whereas the contact angle was reduced from 104.8° to 59.3°. MTT assay, acridine orange/ethidium bromide (AO/EB) fluorescent staining, and SEM were adopted to assess the behavior of the seeded chondrocytes on scaffolds, and it was found that the ternary surface coating stimulated the cell proliferation, viability, and adhesion. Moreover, the coated scaffolds showed higher expression levels of collagen II and aggrecan genes at day 7 compared to the control groups. Therefore, the fabricated PU-3% (w/v) GG-HA-GA scaffold can be considered as a promising scaffold for meniscus tissue engineering.
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Affiliation(s)
- Farshad Amiri
- Department of Biomaterials, Tissue Engineering and Nanotechnology, School of Advanced Medical Technologies, Isfahan University of Medical Sciences (IUMS), Isfahan, Iran
| | - Melika Babaei
- Department of Biomedical Engineering, Faculty of Engineering, University of Isfahan, Isfahan, Iran
| | - Nima Jamshidi
- Department of Biomedical Engineering, Faculty of Engineering, University of Isfahan, Isfahan, Iran.
| | - Maria Agheb
- Department of Biomaterials, Tissue Engineering and Nanotechnology, School of Advanced Medical Technologies, Isfahan University of Medical Sciences (IUMS), Isfahan, Iran
| | - Mohammad Rafienia
- Biosensor Research Center (BRC), Isfahan University of Medical Sciences (IUMS), Isfahan, Iran
| | - Mohammad Kazemi
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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Wang Y, Guo X, Fan X, Zhang H, Xue D, Pan Z. The protective effect of mangiferin on osteoarthritis: An in vitro and in vivo study. Physiol Res 2022; 71:135-145. [PMID: 35043648 PMCID: PMC8997682 DOI: 10.33549/physiolres.934747] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 11/02/2021] [Indexed: 11/25/2022] Open
Abstract
Mangiferin is a kind of polyphenol chemical compound separated from these herbal medicines of Mangifera indica L., Anemarrhena asphodeloides Bge. and Belamcanda chinensis L., which has anti-inflammatory, anti-virus, and other physiological activities without toxic effects. Osteoarthritis (OA) is a chronic disease that is also a kind of arthritis disease in which articular cartilage or bones under the joint is damaged. In addition, artificial replacements are required in severe cases. At present, there are not too much researches on the potential biological activities of mangiferin that plays a protective role in the treatment of OA. In this study, we evaluated the protective effect of mangiferin on osteoarthritis (OA) in vitro and in vivo. First, the effect of different concentrations of mangiferin on rat chondrocytes was determined by MTT assay. Second, the effects of mangiferin on the expression levels of matrix metalloproteinase (MMP)-13, TNF alpha, Collagen II, Caspase-3, and cystatin-C in interleukin-1beta (IL-1beta)-induced rat chondrocytes were examined by the real-time polymerase chain reaction in vitro, meanwhile the effects of mangiferin on the nuclear factor kappa-B (NF-kappaB) signaling pathway were also investigated by Western Blot. Finally, the anti-osteoarthritic protective effect of mangiferin was evaluated in the rat model by anterior cruciate ligament transection (ACLT) combined with bilateral ovariectomy-induced OA in vivo. The results showed that the mangiferin was found to inhibit the expression of MMP-13, TNF-alpha, and Caspase-3 which also increased the expression of Collagen II and cystatin-C in IL 1beta induced rat chondrocytes. In addition, IL-1beta-induced activation of nuclear factor kappa-B (NF-kappaB) and the degradation of inhibitor of kappaB (IkappaB)-alpha were suppressed by mangiferin. For the in vivo study in a rat model of OA, 100 microl of mangiferin was administered by intra-articular injections for rats, the results showed that the cartilage degradation was suppressed by mangiferin through Micro CT and Histological Examination. According to both in vitro and in vivo results, mangiferin has a protective effect in the treatment of OA which may be a promising therapeutic agent for OA.
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Affiliation(s)
- Y Wang
- Department of Orthopaedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. and
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Raja V, Gu Y, Lee HM, Deng J, Prestwich G, Ryan M. SAGE: Novel Therapy to Reduce Inflammation in a Naturally Occurring-Dog Model of Periodontal Disease. J Exp Pharmacol 2022; 14:117-129. [PMID: 35386747 PMCID: PMC8977225 DOI: 10.2147/jep.s353757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 03/22/2022] [Indexed: 11/23/2022] Open
Abstract
Objective Methods Results Conclusion
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Affiliation(s)
- Veena Raja
- Department of Oral Biology and Pathology, Stony Brook School of Dental Medicine, Stony Brook, NY, USA
- Correspondence: Veena Raja, Department of Oral Biology and Pathology, School of Dental medicine, Stony Brook University, Stony Brook, NY, 11794-8706, USA, Tel +1 516-813-6250, Fax +1 631 632-9705, Email
| | - Ying Gu
- Department of General Dentistry, Stony Brook School of Dental Medicine, Stony Brook, NY, USA
| | - Hsi-Ming Lee
- Department of Oral Biology and Pathology, Stony Brook School of Dental Medicine, Stony Brook, NY, USA
| | - Jie Deng
- Department of Oral Biology and Pathology, Stony Brook School of Dental Medicine, Stony Brook, NY, USA
| | - Glenn Prestwich
- Department of Medicinal Chemistry, The University of Utah, Salt Lake City, UT, USA
- Health Sciences Spokane, Washington State University, Spokane, WA, USA
| | - Maria Ryan
- Colgate and Palmolive Company, Piscataway, NJ, USA
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Vafaei S, Wu X, Tu J, Nematollahi-mahani SN. The Effects of Crocin on Bone and Cartilage Diseases. Front Pharmacol 2022; 12:830331. [PMID: 35126154 PMCID: PMC8807478 DOI: 10.3389/fphar.2021.830331] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 12/28/2021] [Indexed: 12/16/2022] Open
Abstract
Crocin, the main biologically active carotenoid of saffron, generally is derived from the dried trifid stigma of Crocus sativus L. Many studies have demonstrated that crocin has several therapeutic effects on biological systems through its anti-oxidant and anti-inflammatory properties. The wide range of crocin activities is believed to be because of its ability to anchor to many proteins, triggering some cellular pathways responsible for cell proliferation and differentiation. It also has therapeutic potentials in arthritis, osteoarthritis, rheumatoid arthritis, and articular pain probably due to its anti-inflammatory properties. Anti-apoptotic effects, as well as osteoclast inhibition effects of crocin, have suggested it as a natural substance to treat osteoporosis and degenerative disease of bone and cartilage. Different mechanisms underlying crocin effects on bone and cartilage repair have been investigated, but remain to be fully elucidated. The present review aims to undertake current knowledge on the effects of crocin on bone and cartilage degenerative diseases with an emphasis on its proliferative and differentiative properties in mesenchymal stem cells.
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Affiliation(s)
- Shayan Vafaei
- Department of Anatomical Science, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Xuming Wu
- Key Laboratory of Anti-Inflammatory and Immune Medicine, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Institute of Clinical Pharmacology, Anhui Medical University, Ministry of Education, Hefei, China
| | - Jiajie Tu
- Key Laboratory of Anti-Inflammatory and Immune Medicine, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Institute of Clinical Pharmacology, Anhui Medical University, Ministry of Education, Hefei, China
- *Correspondence: Jiajie Tu, ; Seyed Noureddin Nematollahi-mahani,
| | - Seyed Noureddin Nematollahi-mahani
- Department of Anatomical Science, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
- *Correspondence: Jiajie Tu, ; Seyed Noureddin Nematollahi-mahani,
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Naumov AV, Vorobyeva NM, Khovasova NO, Moroz VI, Meshkov AD, Manevich TM, Tkacheva ON, Kotovskaya YV, Selezneva EV, Ovcharova LN. The prevalence of osteoarthritis and its association with geriatric syndromes in people over 65: data from the Russian epidemiological study EVKALIPT. TERAPEVT ARKH 2022; 93:1482-1490. [DOI: 10.26442/00403660.2021.12.201268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 01/14/2022] [Indexed: 11/22/2022]
Abstract
Background. Osteoarthritis (OA) in elderly and senile patients is not only common, but also one of the main diseases affecting the duration of active life, its quality, the appearance of addictions and loss of autonomy. Data on the relationship between OA and geriatric syndromes (GS) in our country are extremely scarce.
Aim. To estimate the prevalence of OA and to analyze its associations with HS in persons aged 65 years.
Materials and methods. The study included 4308 people (30% of men) aged 65 to 107 years, living in 11 regions of Russia. The patients were divided into 2 groups: with OA (n=2464) and without OA (n=1821). All patients underwent a comprehensive geriatric assessment.
Results. The prevalence of OA was 57.6%. With age, the frequency of OA increased significantly. According to the results of a comprehensive geriatric assessment, patients with OA had lower walking speed, the sum of points on the Bartel, Lawton scales and a short battery of physical functioning tests and higher the sum of points on the geriatric scale of depression and the age is not a hindrance scale. Patients with OA rated the quality of life and health status lower and higher the intensity of pain syndrome. Patients with OA were more likely to use any assistive device, with the exception of a wheelchair. In patients with OA, the most common HS were chronic pain syndrome (92%), senile asthenia syndrome (64%), basic (66%) and instrumental (56%) dependence in everyday life, cognitive impairment (62%), probable depression (51%) and urinary incontinence (50%). Univariate regression analysis showed that OA is associated with a 1.23.0-fold increase in the risk of a number of GS and a 28% decrease in the risk of malnutrition.
Conclusion. OA is widespread in the elderly population. The presence of OA is associated with a number of GS associated with loss of autonomy.
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Kantor ED, O'Connell K, Liang PS, Navarro SL, Giovannucci EL, Du M. Glucosamine Use and Risk of Colorectal Cancer: Results from UK Biobank. Cancer Epidemiol Biomarkers Prev 2022; 31:647-653. [PMID: 35027430 DOI: 10.1158/1055-9965.epi-21-1171] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/29/2021] [Accepted: 01/12/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Use of the dietary supplement glucosamine has been associated with reduced risk of colorectal cancer (CRC); however, it remains unclear if the association varies by screening status, time, and other factors. METHODS We therefore evaluated these questions in UK Biobank. Multivariable-adjusted Hazard Ratios (HRs) and 95% Confidence Intervals (95% CI) were estimated using Cox proportional hazards regression. RESULTS No association was observed between use of glucosamine and risk of CRC overall (HR: 0.94; 95% CI: 0.85-1.04). However, the association varied by screening status (p-interaction:0.05), with an inverse association observed only among never-screened individuals (HR: 0.86; 95% CI: 0.76-0.98). When stratified by study time, an inverse association was observed in early follow-up among those entering the cohort in early years (2006-2008, HR: 0.80; 95% CI: 0.67-0.95). No heterogeneity was observed by age, sex, body mass index, smoking status, or use of non-steroidal anti-inflammatory drugs. CONCLUSIONS While there was no association between glucosamine use and CRC overall, the inverse association among never-screened individuals mirrors our observations in prior exploratory analyses of US cohorts. The National Health Service Bowel Cancer Screening Program started in 2006 in England and was more widely implemented across the UK by 2009. In line with this, we observed an inverse association limited to early follow-up in those surveyed 2006-2008, before screening was widely implemented. IMPACT These data suggest that unscreened individuals may benefit from use of glucosamine; however, further studies are needed to confirm the interplay of screening and timing.
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Affiliation(s)
- Elizabeth D Kantor
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center
| | - Kelli O'Connell
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center
| | - Peter S Liang
- Medicine, Division of Gastroenterology and Hepatology, NYU Langone Health
| | - Sandi L Navarro
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center
| | | | - Mengmeng Du
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center
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Dhami M, Raj K, Singh S. Neuroprotective Effect of Fucoxanthin against Intracerebroventricular Streptozotocin (ICV-STZ) Induced Cognitive Impairment in Experimental Rats. Curr Alzheimer Res 2021; 18:623-637. [PMID: 34792011 DOI: 10.2174/1567205018666211118144602] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 08/27/2021] [Accepted: 10/21/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Alzheimer's disease (AD) is a neurological disorder characterized by loss of memory and cognitive functions caused by oxidative stress, neuroinflammation, change in neurotransmitter levels, and excessive deposition of Aβ(1-42) plaques. Fucoxanthin is a carotenoid with potential antioxidant, anti-inflammatory, and neuroprotective actions. OBJECTIVE In the present study, fucoxanthin was employed as a protective strategy in Intracerebroventricular Streptozotocin (ICV-STZ) induced experimental model of cognitive impairment. METHODS STZ was injected twice ICV (3 mg/kg) on alternate days 1 and 3, and Wistar rats were evaluated for the memory analysis using Morris water maze and elevated plus-maze. Fucoxanthin at low 50 mg/kg, p.o. and high dose 100 mg/kg, p.o. was administered for 14 days. All animals were sacrificed on day 29, and brain hippocampus tissue after isolation was used for biochemical (MDA, nitrite, GSH, SOD and Catalase), neuroinflammatory (TNF-α, IL-1β, and IL-6), neurotransmitters (ACh, GABA Glutamate), Aβ(1-42) and Tau protein measurements. RESULTS STZ-infused rats showed significant impairment in learning and memory, increased oxidative stress (MDA, nitrite), reduced antioxidant defense (GSH, SOD and Catalase), promoted cytokine release, and change in neurotransmitters level. However, fucoxanthin improved cognitive functions, restored antioxidant levels, reduced inflammatory markers dose-dependently, and restored neurotransmitters concentration. CONCLUSION The finding of the current study suggests that fucoxanthin could be the promising compound for improving cognitive functions through antioxidant, anti-inflammatory, and neuroprotective mechanisms, and inhibition of acetylcholinesterase (AChE) enzyme activities, Aβ(1-42) accumulation, and tau protein.
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Affiliation(s)
- Mahadev Dhami
- Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab 142001, India
| | - Khadga Raj
- Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab 142001, India
| | - Shamsher Singh
- Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab 142001, India
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Gu Y, Raja V, Lee HM, Hong H, Prestwich G, Ryan ME. Therapeutic potential of a novel semi-synthetic-sulfated-polysaccharide to suppress inflammatory mediators in P. gingivalis LPS stimulated human monocytes/macrophages. JOURNAL OF INFLAMMATION-LONDON 2021; 18:26. [PMID: 34481488 PMCID: PMC8418013 DOI: 10.1186/s12950-021-00292-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 08/06/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Chronic periodontitis is associated with an increased risk for systemic conditions such as cardiovascular disease, diabetes, and osteoporosis. During chronic periodontitis, endotoxin (lipopolysaccharide, LPS) produced by P. gingivalis provokes monocyte accumulation and differentiation into macrophages and increased secretion of pro-inflammatory cytokines and matrix metalloproteases (MMPs). While normal levels of MMPs are important in cellular function, increased levels of cytokines and MMPs can cause connective tissue destruction. RESULTS In the current study, we investigated the therapeutic capability of a novel semi-synthetic sulfated polysaccharide (SAGE) on the production of cytokines and MMPs by cultured human mononuclear cells and macrophages stimulated with endotoxin LPS produced by P. gingivalis, a periodontally-relevant cell culture model. Our research demonstrated SAGE inhibited the LPS induced synthesis of inflammatory mediators including TNF-α, IL-1β, PGE2, and MMP-9 in this periodontal-relevant cell culture model. In addition, TLR-2 and TLR-4 levels were also reduced with the SAGE treatment. CONCLUSIONS The therapeutic potential of this novel semi-synthetic sulfated polysaccharide compound may help to prevent tissue damage and bone loss in patients with periodontal disease or other inflammatory diseases.
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Affiliation(s)
- Ying Gu
- Departments of General Dentistry, School of Dental Medicine, Stony Brook University, Stony Brook, NY, 11794, USA.
| | - Veena Raja
- Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY, 11794, USA
| | - Hsi-Ming Lee
- Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY, 11794, USA
| | - Houlin Hong
- Program in Public Health, Stony Brook Medicine, Stony Brook University, Stony Brook, NY, 11794, USA
| | - Glenn Prestwich
- Department of Medicinal Chemistry, The University of Utah, Salt Lake City, UT, 84112, USA.,Health Sciences Spokane, Washington State University Health Sciences, Spokane, WA, 99202, USA
| | - Maria E Ryan
- Colgate Palmolive Company, Piscataway, NJ, 08854, USA
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A Combination of Celecoxib and Glucosamine Sulfate Has Anti-Inflammatory and Chondroprotective Effects: Results from an In Vitro Study on Human Osteoarthritic Chondrocytes. Int J Mol Sci 2021; 22:ijms22168980. [PMID: 34445685 PMCID: PMC8396455 DOI: 10.3390/ijms22168980] [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: 07/07/2021] [Revised: 08/13/2021] [Accepted: 08/17/2021] [Indexed: 01/08/2023] Open
Abstract
This study investigated the possible anti-inflammatory and chondroprotective effects of a combination of celecoxib and prescription-grade glucosamine sulfate (GS) in human osteoarthritic (OA) chondrocytes and their possible mechanism of action. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination with IL-1β (10 ng/mL) and a specific nuclear factor (NF)-κB inhibitor (BAY-11-7082, 1 µM). Gene expression and release of some pro-inflammatory mediators, metalloproteinases (MMPs), and type II collagen (Col2a1) were evaluated by qRT-PCR and ELISA; apoptosis and mitochondrial superoxide anion production were assessed by cytometry; B-cell lymphoma (BCL)2, antioxidant enzymes, and p50 and p65 NF-κB subunits were analyzed by qRT-PCR. Celecoxib and GS alone or co-incubated with IL-1β significantly reduced expression and release of cyclooxygenase (COX)-2, prostaglandin (PG)E2, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and MMPs, while it increased Col2a1, compared to baseline or IL-1β. Both drugs reduced apoptosis and superoxide production; reduced the expression of superoxide dismutase, catalase, and nuclear factor erythroid; increased BCL2; and limited p50 and p65. Celecoxib and GS combination demonstrated an increased inhibitory effect on IL-1β than that observed by each single treatment. Drugs effects were potentiated by pre-incubation with BAY-11-7082. Our results demonstrated the synergistic effect of celecoxib and GS on OA chondrocyte metabolism, apoptosis, and oxidative stress through the modulation of the NF-κB pathway, supporting their combined use for the treatment of OA.
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Ammendolia A, Marotta N, Marinaro C, Demeco A, Mondardini P, Costantino C. The synergic use of the High Power Laser Therapy and Glucosamine sulfate in Knee osteoarthritis: A Randomized Controlled Trial. ACTA BIO-MEDICA : ATENEI PARMENSIS 2021; 92:e2021237. [PMID: 34212917 PMCID: PMC8343723 DOI: 10.23750/abm.v92i3.10952] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Accepted: 11/16/2020] [Indexed: 11/23/2022]
Abstract
Background and aim: To determine the efficacy of the synergistic use of High Power Laser Therapy (HPLT) with glucosamine sulfate (GS) in knee osteoarthritis. Methods: This 2-arm randomized controlled trial (RCT) enrolled 90 subjects (M=53, F=37, y= 55±11.2) and randomly allocated using a stratified sampling method in experimental group (A) with HPLT+GS 1500mg (GS - Dona®, Rottapharm, Monza, Italy) (n=45) or in a control group (B) with HPLT + placebo (n=45). Results: VAS score in Activities of day Living (ADL), Standardized stair climb test (SSCT), Zohlen’s sign (RASPING) and Rabot test were used, to evaluate patients at the beginning of the study (T0), at 2 months (T1) and at 6 months (T2). In the mean scores for VAS in ADL, SSCT, RABOT and RASPING at T1, no significant differences were found between the experimental and the control group with paired T and ANOVA test. But significant differences between groups (p<0.05) in all outcomes were observed at 6 months (T2). Conclusions: HPLT is useful in treating knee osteoarthritis, but when combined with Glucosamine Sulfate, thanks to the synergy of two interventions, can achieve a long-term effect up to 6 months after treatment. (www.actabiomedica.it)
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Affiliation(s)
| | - Nicola Marotta
- Department of Surgical and Medical Sciences, University of Catanzaro "Magna Graecia" Italy.
| | - Cinzia Marinaro
- Department of Surgical and Medical Sciences, University of Catanzaro "Magna Graecia" Italy.
| | - Andrea Demeco
- Department of Surgical and Medical Sciences, University of Catanzaro "Magna Graecia" Italy.
| | | | - Cosimo Costantino
- Department of Medicine and Surgery, University of Parma, Parma, Italy.
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Chondroprotection and Molecular Mechanism of Action of Phytonutraceuticals on Osteoarthritis. Molecules 2021; 26:molecules26082391. [PMID: 33924083 PMCID: PMC8074261 DOI: 10.3390/molecules26082391] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 04/16/2021] [Accepted: 04/17/2021] [Indexed: 02/06/2023] Open
Abstract
Osteoarthritis (OA) is a degenerative joint disease and an important cause of incapacitation. There is a lack of drugs and effective treatments that stop or slow the OA progression. Modern pharmacological treatments, such as analgesics, have analgesic effects but do not affect the course of OA. Long-term use of these drugs can lead to serious side effects. Given the OA nature, it is likely that lifelong treatment will be required to stop or slow its progression. Therefore, there is an urgent need for disease-modifying OA treatments that are also safe for clinical use over long periods. Phytonutraceuticals are herbal products that provide a therapeutic effect, including disease prevention, which not only have favorable safety characteristics but may have an alleviating effect on the OA and its symptoms. An estimated 47% of OA patients use alternative drugs, including phytonutraceuticals. The review studies the efficacy and action mechanism of widely used phytonutraceuticals, analyzes the available experimental and clinical data on the effect of some phytonutraceuticals (phytoflavonoids, polyphenols, and bioflavonoids) on OA, and examines the known molecular effect and the possibility of their use for chondroprotection.
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Kantor ED, O'Connell K, Du M, Cao C, Zhang X, Lee DH, Cao Y, Giovannucci EL. Glucosamine and Chondroitin Use in Relation to C-Reactive Protein Concentration: Results by Supplement Form, Formulation, and Dose. J Altern Complement Med 2021; 27:150-159. [PMID: 33290138 PMCID: PMC7891193 DOI: 10.1089/acm.2020.0283] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Objectives: Glucosamine and chondroitin supplements have been associated with reduced inflammation, as measured by C-reactive protein (CRP). It is unclear if associations vary by formulation (glucosamine alone vs. glucosamine+chondroitin), form (glucosamine hydrochloride vs. glucosamine sulfate), or dose. Design, Subjects, Setting, Location: The authors evaluated these questions using cross-sectional data collected between 1999 and 2010 on 21,917 US adults, surveyed as part of the National Health and Nutrition Examination Survey (NHANES). Exposures: Glucosamine and chondroitin use was assessed during an in-home interview; exposures include supplement formulation, form, and dose. Outcome/Analysis: CRP was measured using blood collected at interview. Survey-weighted linear regression was used to evaluate the multivariable-adjusted association between exposures and log-transformed CRP. Results: In early years (1999-2004), use of glucosamine (ratio = 0.87; 95% confidence interval [CI] = 0.79-0.96) and chondroitin (ratio = 0.83; 95% CI = 0.72-0.95) was associated with reduced CRP. However, associations significantly varied by calendar time (p-interaction = 0.04 and p-interaction = 0.01, respectively), with associations nonsignificant in later years (ratio = 1.09; 95% CI = 0.94-1.28 and ratio = 1.16; 95% CI = 0.99-1.35, respectively). Consequently, all analyses have been stratified by calendar time. Associations did not significantly differ by formulation in either set of years; however, significant associations were observed for combined use of glucosamine+chondroitin (ratioearly = 0.82; 95% CI = 0.72-0.95; ratiolate = 1.16; 1.00-1.35), but not glucosamine alone. Associations also did not significantly differ by supplement form. Even so, a significant inverse association was observed only for glucosamine sulfate in the early years (ratio = 0.78; 95% CI = 0.64-0.95); no significant association was observed for glucosamine hydrochloride. No significant trends were observed by dose. Conclusions: Although a significant inverse association was observed for glucosamine and chondroitin and CRP in early years, this association did not hold in later years. This pattern held for combined use of glucosamine+chondroitin as well as glucosamine sulfate, although associations did not significantly vary by supplement form, formulation, or dose. Further study is needed to better understand these associations in the context of calendar time.
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Affiliation(s)
- Elizabeth D. Kantor
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kelli O'Connell
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mengmeng Du
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Chao Cao
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, St. Louis, MO, USA
| | - Xuehong Zhang
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Dong Hoon Lee
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Yin Cao
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, St. Louis, MO, USA
- Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, St Louis, MO, USA
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, St Louis, MO, USA
| | - Edward L. Giovannucci
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
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Veronese N, Demurtas J, Smith L, Reginster JY, Bruyère O, Beaudart C, Honvo G, Maggi S. Glucosamine sulphate: an umbrella review of health outcomes. Ther Adv Musculoskelet Dis 2020; 12:1759720X20975927. [PMID: 33488785 PMCID: PMC7768322 DOI: 10.1177/1759720x20975927] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 11/03/2020] [Indexed: 12/15/2022] Open
Abstract
Background and Aims: Glucosamine sulphate (GS) can be used as background therapy in people affected by knee osteoarthritis (OA). Knowledge regarding the efficacy and safety of GS is of importance since its use worldwide is increasing. Therefore, the present study aimed to map and grade the diverse health outcomes associated with GS using an umbrella review approach. Methods: Medline, Cinahl and Embase databases were searched until 1 April 2020. An umbrella review of systematic reviews and meta-analyses of randomized controlled trials (RCTs) was carried out. The evidence from the RCTs was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Results: From 140 articles returned, 11 systematic reviews, for a total of 21 outcomes (37 RCTs; 3949 participants; almost all using 1500 mg/day), were included. No systematic reviews/meta-analyses of observational studies were included. Regarding the findings of the meta-analyses, 9/17 outcomes were statistically significant, indicating that GS is more effective than placebo. A high certainty of evidence, as assessed by GRADE, supported the use of GS (versus placebo) in improving the Lequesne Index, joint space width change, joint space width change after 3 years of follow up, joint space narrowing and OA progression. No difference in terms of adverse effects was found between GS and placebo. In systematic reviews, GS was associated with a better glucose profile and a better physical function performance than placebo. Conclusion: GS, when used as a prescription drug (i.e. crystalline glucosamine sulphate) at 1500 mg daily dosage, can positively affect the cartilage structure, reduce pain, improve function and glucose metabolism in people with knee OA, without having a greater incidence of adverse effects than placebo.
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Affiliation(s)
- Nicola Veronese
- Geriatric Unit, Department of Internal Medicine and Geriatrics, University of Palermo, Viale Scaduto, Palermo, 90100, Italy
| | - Jacopo Demurtas
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Lee Smith
- The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, UK
| | - Jean-Yves Reginster
- Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
| | - Olivier Bruyère
- Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
| | - Charlotte Beaudart
- Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
| | - Germain Honvo
- Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
| | - Stefania Maggi
- National Research Council, Neuroscience Institute, Padua, Italy
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Prostanoid Receptor Subtypes and Its Endogenous Ligands with Processing Enzymes within Various Types of Inflammatory Joint Diseases. Mediators Inflamm 2020; 2020:4301072. [PMID: 33273889 PMCID: PMC7676943 DOI: 10.1155/2020/4301072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 10/21/2020] [Indexed: 11/18/2022] Open
Abstract
A complex inflammatory process mediated by proinflammatory cytokines and prostaglandins commonly occurs in the synovial tissue of patients with joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). This study systematically investigated the distinct expression profile of prostaglandin E2 (PGE2), its processing enzymes (COX-2), and microsomal PGES-1 (mPGES-1) as well as the corresponding prostanoid receptor subtypes (EP1-4) in representative samples of synovial tissue from these patients (JT, OA, and RA). Quantitative TaqMan®-PCR and double immunofluorescence confocal microscopy of synovial tissue determined the abundance and exact immune cell types expressing these target molecules. Our results demonstrated that PGE2 and its processing enzymes COX-2 and mPGES-1 were highest in the synovial tissue of RA, followed by the synovial tissue of OA and JT patients. Corresponding prostanoid receptor, subtypes EP3 were highly expressed in the synovium of RA, followed by the synovial tissue of OA and JT patients. These proinflammatory target molecules were distinctly identified in JT patients mostly in synovial granulocytes, in OA patients predominantly in synovial macrophages and fibroblasts, whereas in RA patients mainly in synovial fibroblasts and plasma cells. Our findings show a distinct expression profile of EP receptor subtypes and PGE2 as well as the corresponding processing enzymes in human synovium that modulate the inflammatory process in JT, OA, and RA patients.
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Wang C, Gao Y, Zhang Z, Chi Q, Liu Y, Yang L, Xu K. Safflower yellow alleviates osteoarthritis and prevents inflammation by inhibiting PGE2 release and regulating NF-κB/SIRT1/AMPK signaling pathways. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2020; 78:153305. [PMID: 32871523 DOI: 10.1016/j.phymed.2020.153305] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 08/04/2020] [Accepted: 08/17/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND Safflower yellow (SY) is the main active ingredient of safflower, with various pharmacological effects such as anticoagulating, antioxidant, and anti-arthritis effects. PURPOSE To investigate the anti-inflammatory and chondrocyte protecting role of SY, which subsequently leads to the inhibition of cartilage degradation. METHODS Rat chondrocytes were stimulated with tumor necrosis factor α (TNF-α) with or without SY treatment. Following this, CCK-8 assay was performed to detect cytotoxicity. RT-qPCR, Western blotting, and immunofluorescence staining were used to detect the gene/protein expression of typical cartilage matrix genes and related inflammatory markers. Subsequently, EdU assay was used to evaluate cell proliferation. RNA sequencing, online target prediction, and molecular docking were performed to determine the possible molecular targets and pathways. RESULTS The results showed that SY restored the TNF-α-induced up-regulation of IL-1β, PTGS2, and MMP-13 and down-regulation of COL2A1 and ACAN. Furthermore, it recovered cell proliferation by suppressing TNF-α. Gene expression profiles identified 717 differentially expressed genes (DEGs) in the cells cultured with or without SY under TNF-α stimulation. After pathway enrichment, PI3K-Akt, TNF, Cytokine-cytokine receptor interaction, NF-κB, NOD-like receptor, and Chemokine signaling pathways were notably selected to highlight NFKBIA, CCL5, CCL2, IL6, and TNF as potential targets in osteoarthritis (OA). SY inhibited TNF-α-induced activation of NF-κB and endoplasmic reticulum (ER) stress by promoting AMPK phosphorylation along with SIRT1 expression. Further, SY reduced MMP-13 expression and targeted COX-2 for decreasing PGE2 release. In addition, anterior cruciate ligament transection-induced OA was ameliorated by local administration of SY. CONCLUSION These results demonstrate that SY protects chondrocytes and inhibits inflammation by regulating the NF-κB/SIRT1/AMPK pathways and ER stress, thus preventing cartilage degeneration in OA.
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Affiliation(s)
- Chunli Wang
- Hubei Engineering Technology Research Center of TCM Processing, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China; National Innovation and Attracting Talents "111" base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China
| | - Yan Gao
- National Innovation and Attracting Talents "111" base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China
| | - Zike Zhang
- National Innovation and Attracting Talents "111" base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China
| | - Qingjia Chi
- Hubei Key Laboratory of Theory and Application of Advanced Materials Mechanics, Department of Mechanics and Engineering Structure, Wuhan University of Technology, China
| | - Yanju Liu
- Hubei Engineering Technology Research Center of TCM Processing, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China
| | - Li Yang
- National Innovation and Attracting Talents "111" base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China
| | - Kang Xu
- Hubei Engineering Technology Research Center of TCM Processing, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
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Lee DH, Cao C, Zong X, Zhang X, O'Connell K, Song M, Wu K, Du M, Cao Y, Giovannucci EL, Kantor ED. Glucosamine and Chondroitin Supplements and Risk of Colorectal Adenoma and Serrated Polyp. Cancer Epidemiol Biomarkers Prev 2020; 29:2693-2701. [PMID: 33055203 DOI: 10.1158/1055-9965.epi-20-0805] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 08/17/2020] [Accepted: 09/22/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Studies have shown an inverse association between use of glucosamine and chondroitin supplements and colorectal cancer risk. However, the association with the precursor lesion, colorectal adenoma and serrated polyp, has not been examined. METHODS Analyses include 43,163 persons from the Nurses' Health Study (NHS), Health Professionals Follow-up Study (HPFS), and NHS2 who reported on glucosamine/chondroitin use in 2002 and who subsequently underwent ≥1 lower gastrointestinal endoscopy. By 2012, 5,715 conventional (2,016 high-risk) adenomas were detected, as were 4,954 serrated polyps. Multivariable logistic regression for clustered data was used to calculate OR and 95% confidence intervals (CI). RESULTS Glucosamine/chondroitin use was inversely associated with high risk and any conventional adenoma in NHS and HPFS: in the pooled multivariable-adjusted model, glucosamine + chondroitin use at baseline was associated with a 26% (OR = 0.74; 95% CI, 0.60-0.90; P heterogeneity = 0.23) and a 10% (OR = 0.90; 95% CI, 0.81-0.99; P heterogeneity = 0.36) lower risk of high-risk adenoma and overall conventional adenoma, respectively. However, no association was observed in NHS2, a study of younger women (high-risk adenoma: OR = 1.09; 95% CI, 0.82-1.45; overall conventional adenoma: OR = 1.00; 95% CI, 0.86-1.17), and effect estimates pooled across all three studies were not significant (high-risk: OR = 0.83; 95% CI, 0.63-1.10; P heterogeneity = 0.03; overall conventional adenoma: OR = 0.93; 95% CI, 0.85-1.02; P heterogeneity = 0.31). No associations were observed for serrated polyps. CONCLUSIONS Glucosamine/chondroitin use was associated with lower risks of high-risk and overall conventional adenoma in older adults; however, this association did not hold in younger women, or for serrated polyps. IMPACT Our study suggests that glucosamine and chondroitin may act on early colorectal carcinogenesis in older adults.
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Affiliation(s)
- Dong Hoon Lee
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
| | - Chao Cao
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri
| | - Xiaoyu Zong
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri
| | - Xuehong Zhang
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Kelli O'Connell
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Mingyang Song
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Mengmeng Du
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Yin Cao
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri
| | - Edward L Giovannucci
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.,Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Elizabeth D Kantor
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
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Semiz A, Duman O, Tunç S. Development of a reversed phase-high performance liquid chromatographic method for the analysis of glucosamine sulphate in dietary supplement tablets. J Food Compost Anal 2020. [DOI: 10.1016/j.jfca.2020.103607] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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