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1.
Regen Biomater ; 11: rbae049, 2024.
Article in English | MEDLINE | ID: mdl-38919844

ABSTRACT

Microbial infections of bones, particularly after joint replacement surgery, are a common occurrence in clinical settings and often lead to osteomyelitis (OM). Unfortunately, current treatment approaches for OM are not satisfactory. To address this issue, this study focuses on the development and evaluation of an injectable magnesium oxide (MgO) nanoparticle (NP)-coordinated phosphocreatine-grafted chitosan hydrogel (CMPMg-VCM) loaded with varying amounts of vancomycin (VCM) for the treatment of OM. The results demonstrate that the loading of VCM does not affect the formation of the injectable hydrogel, and the MgO-incorporated hydrogel exhibits anti-swelling properties. The release of VCM from the hydrogel effectively kills S.aureus bacteria, with CMPMg-VCM (50) showing the highest antibacterial activity even after prolonged immersion in PBS solution for 12 days. Importantly, all the hydrogels are non-toxic to MC3T3-E1 cells and promote osteogenic differentiation through the early secretion of alkaline phosphatase and calcium nodule formation. Furthermore, in vivo experiments using a rat OM model reveal that the CMPMg-VCM hydrogel effectively kills and inhibits bacterial growth, while also protecting the infected bone from osteolysis. These beneficial properties are attributed to the burst release of VCM, which disrupts bacterial biofilm, as well as the release of Mg ions and hydroxyl by the degradation of MgO NPs, which inhibits bacterial growth and prevents osteolysis. Overall, the CMPMg-VCM hydrogel exhibits promising potential for the treatment of microbial bone infections.

2.
Biomater Adv ; 161: 213893, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38796955

ABSTRACT

Angiogenesis plays a crucial role in bone regeneration. Hypoxia is a driving force of angiogenesis at the initial stage of tissue repair. The hypoxic microenvironment could activate the hypoxia-inducible factor (HIF)-1α signaling pathway in cells, thereby enhancing the proliferation, migration and pro-angiogenic functions of stem cells. However, long-term chronic hypoxia could inhibit osteogenic differentiation and even lead to apoptosis. Therefore, shutdown of the HIF-1α signaling pathway and providing oxygen at later stage probably facilitate osteogenic differentiation and bone regeneration. Herein, an oxygen tension regulating hydrogel that sequentially activate and deactivate the HIF-1α signaling pathway were prepared in this study. Its effect and mechanism on stem cell differentiation were investigated both in vitro and in vivo. We proposed a gelatin-based hydrogel capable of sequentially delivering a hypoxic inducer (copper ions) and oxygen generator (calcium peroxide). The copper ions released from the hydrogels significantly enhanced cell viability and VEGF secretion of BMSCs via upregulating HIF-1α expression and facilitating its translocation into the nucleus. Additionally, calcium peroxide promoted alkaline phosphatase activity, osteopontin secretion, and calcium deposition through the activation of ERK1/2. Both Cu2+ and calcium peroxide demonstrated osteogenic promotion individually, while their synergistic effect within the hydrogels led to a superior osteogenic effect by potentially activating the HIF-1α and ERK1/2 signaling pathways.


Subject(s)
Bone Regeneration , Hydrogels , Hypoxia-Inducible Factor 1, alpha Subunit , MAP Kinase Signaling System , Mesenchymal Stem Cells , Neovascularization, Physiologic , Osteogenesis , Oxygen , Hydrogels/pharmacology , Hydrogels/chemistry , Osteogenesis/drug effects , Osteogenesis/physiology , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Bone Regeneration/drug effects , Animals , Neovascularization, Physiologic/drug effects , Neovascularization, Physiologic/physiology , Oxygen/metabolism , MAP Kinase Signaling System/drug effects , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/drug effects , Cell Differentiation/drug effects , Gelatin , Cell Survival/drug effects , Signal Transduction/drug effects , Peroxides
3.
J Transl Med ; 22(1): 504, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802944

ABSTRACT

BACKGROUND: A former cohort study has raised concern regarding the unanticipated hazard of omeprazole in expediting osteoarthritis (OA) advancement. The precise nature of their causal evidence, however, remains undetermined. The present research endeavors to investigate the underlying causal link between omeprazole and OA through the application of mendelian randomization (MR) analysis. METHODS: The study incorporated the ukb-a-106 and ukb-b-14,486 datasets. The investigation of causal effects employed methodologies such as MR-Egger, Weighted median, Inverse variance weighted (IVW) with multiplicative random effects, and IVW (fixed effects). The IVW approach was predominantly considered for result interpretation. Sensitivity analysis was conducted, encompassing assessments for heterogeneity, horizontal pleiotropy, and the Leave-one-out techniques. RESULTS: The outcomes of the MR analysis indicated a causal relationship between omeprazole and OA, with omeprazole identified as a contributing risk factor for OA development (IVW model: OR = 1.2473, P < 0.01 in ukb-a-106; OR = 1.1288, P < 0.05 in ukb-b-14,486). The sensitivity analysis underscored the robustness and dependability of the above-mentioned analytical findings. CONCLUSION: This study, employing MR, reveals that omeprazole, as an exposure factor, elevates the risk of OA. Considering the drug's efficacy and associated adverse events, clinical practitioners should exercise caution regarding prolonged omeprazole use, particularly in populations with heightened OA risks. Further robust and high-quality research is warranted to validate our findings and guide clinical practice.


Subject(s)
Biological Specimen Banks , Mendelian Randomization Analysis , Omeprazole , Osteoarthritis , Humans , Omeprazole/adverse effects , Osteoarthritis/genetics , United Kingdom/epidemiology , Risk Factors , Female , Male , Middle Aged , UK Biobank
4.
Int J Biol Macromol ; 269(Pt 1): 131914, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38703527

ABSTRACT

The healing of critical-sized bone defects is a major challenge in the field of bone tissue engineering. Gelatin-related hydrogels have emerged as a potential solution due to their desirable properties. However, their limited osteogenic, mechanical, and reactive oxygen species (ROS)-scavenging capabilities have hindered their clinical application. To overcome this issue, we developed a biofunctional gelatin-Mxene nanocomposite hydrogel. Firstly, we prepared two-dimensional (2D) Ti3C2 MXene nanosheets using a layer delamination method. Secondly, these nanosheets were incorporated into a transglutaminase (TG) enzyme-containing gallic acid-imbedded gelatin (GGA) pre-gel solution to create an injectable GGA-MXene (GM) nanocomposite hydrogel. The GM hydrogels exhibited superior compressive strength (44-75.6 kPa) and modulus (24-44.5 kPa) compared to the GGA hydrogels. Additionally, the GM hydrogel demonstrated the ability to scavenge reactive oxygen species (OH- and DPPH radicals), protecting MC3T3-E1 cells from oxidative stress. GM hydrogels were non-toxic to MC3T3-E1 cells, increased alkaline phosphatase secretion, calcium nodule formation, and upregulated osteogenic gene expressions (ALP, OCN, and RUNX2). The GM400 hydrogel was implanted in critical-sized calvarial defects in rats. Remarkably, it exhibited significant potential for promoting new bone formation. These findings indicated that GM hydrogel could be a viable candidate for future clinical applications in the treatment of critical-sized bone defects.


Subject(s)
Gelatin , Hydrogels , Nanocomposites , Osteogenesis , Reactive Oxygen Species , Skull , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Gelatin/chemistry , Nanocomposites/chemistry , Osteogenesis/drug effects , Reactive Oxygen Species/metabolism , Skull/drug effects , Skull/pathology , Mice , Rats , Bone Regeneration/drug effects , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Titanium/chemistry , Cell Line , Tissue Engineering/methods
5.
Cancer Epidemiol ; 90: 102577, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705126

ABSTRACT

OBJECTIVE: This study aims to explore the multiple mediating roles of illness acceptance and symptom severity between health locus of control and symptom distress in acute leukemia patients. METHODS: From June 2022 to March 2023, a convenience sampling method was used to recruit 208 acute leukemia patients in the inpatient center of a hospital in Hebei. The Chinese versions of Multidimensional Health Locus of Control Scale, Illness Acceptance Scale, and Anderson Symptom Assessment Scale was used in the cross-sectional study. RESULTS: All participants reported the presence of symptom distress. Symptom distress was significantly correlated with chance health locus of control, illness acceptance, and symptom severity (P<0.05). Illness acceptance alone played a mediating role in the relationship between chance health locus of control and symptom distress in acute leukemia patients (ß=0.087, 95%CI 0.030-0.167). The indirect role of chance health locus of control on symptom distress through symptom severity alone was also statistically significant (ß=0.131, 95%CI 0.008-0.252). Furthermore, the multiple mediating role of chance health locus of control and symptom distress through illness acceptance and symptom severity combined was verified (ß=0.027, 95%CI 0.001-0.089). The alternative model is also valid, indicating bidirectional relationships between symptom severity, illness acceptance, and chance health locus of control, collectively influencing symptom distress. CONCLUSION: There is a positive relationship between chance health locus of control and symptom distress; additionally, increasing social psychological interventions for illness acceptance and strengthening the management of core symptoms will help alleviate the impact of health chance locus of control on symptom distress in acute leukemia patients. Longitudinal studies are needed to confirm the causal relationships among the variables explored within the model. IMPACT ON NURSING PRACTICE: It is recommended that healthcare professionals pay attention to the assessment of health locus of control in patients, identify patients with health chance locus of control in a timely manner, take measures to enhance their disease acceptance, and strengthen the management of core symptoms, thereby reducing their level of symptom distress.


Subject(s)
Internal-External Control , Humans , Male , Female , Cross-Sectional Studies , Adult , Middle Aged , Severity of Illness Index , Leukemia/psychology , Young Adult , Psychological Distress , Surveys and Questionnaires , Aged , China/epidemiology
6.
J Inflamm Res ; 17: 2479-2498, 2024.
Article in English | MEDLINE | ID: mdl-38681072

ABSTRACT

During the past decade, mounting evidence has increasingly linked programmed cell death (PCD) to the progression and development of osteoarthritis (OA). There is a significant need for a thorough scientometric analysis that recapitulates the relationship between PCD and OA. This study aimed to collect articles and reviews focusing on PCD in OA, extracting data from January 1st, 2013, to October 31st, 2023, using the Web of Science. Various tools, including VOSviewer, CiteSpace, Pajek, Scimago Graphica, and the R package, were employed for scientometric and visualization analyses. Notably, China, the USA, and South Korea emerged as major contributors, collectively responsible for more than 85% of published papers and significantly influencing research in this field. Among different institutions, Shanghai Jiao Tong University, Xi'an Jiao Tong University, and Zhejiang University exhibited the highest productivity. Prolific authors included Wang Wei, Wang Jing, and Zhang Li. Osteoarthritis and Cartilage had the most publications in this area. Keywords related to PCD in OA prominently highlighted 'chondrocytes', 'inflammation', and 'oxidative stress', recognized as pivotal mechanisms contributing to PCD within OA. This study presents the first comprehensive scientometric analysis, offering a broad perspective on the knowledge framework and evolving patterns concerning PCD in relation to OA over the last decade. Such insights can aid researchers in comprehensively understanding this field and provide valuable directions for future explorations.

8.
Front Pharmacol ; 15: 1366852, 2024.
Article in English | MEDLINE | ID: mdl-38464725

ABSTRACT

In the past 11 years, there has been a surge in studies exploring the regulatory effect of Traditional Chinese Medicine (TCM) on ferroptosis. However, a significant gap persists in comprehensive scientometric analysis and scientific mapping research, especially in tracking the evolution, primary contributors, and emerging research focal points. This study aims to comprehensively update the advancements in targeting ferroptosis with various TCMs during the previous 11 years. The data, covering the period from 1 January 2012, to 30 November 2023, were retrieved from the Web of Science database. For in-depth scientometric and visualized analyses, a series of advanced analytical instruments were employed. The findings highlight China's predominant role, accounting for 71.99% of total publications and significantly shaping research in this domain. Noteworthy productivity was observed at various institutions, including Guangzhou University of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, and Zhejiang University. Thomas Efferth emerged as the foremost author within this field, while Frontiers in Pharmacology boasted the highest publication count. This study pinpointed hepatocellular carcinoma, chemical and drug-induced liver injury, mitochondrial diseases, acute kidney injury, and liver failure as the most critical disorders addressed in this research realm. The research offers a comprehensive bibliometric evaluation, enhancing our understanding of the present status of TCM therapy in managing ferroptosis-related diseases. Consequently, it aids both seasoned researchers and newcomers by accelerating access to vital information and fostering innovative concept extraction within this specialized field.

9.
Heliyon ; 10(2): e24471, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38298665

ABSTRACT

Knee osteoarthritis (KOA) is one of the most common degenerative diseases and is characterized by cartilage degeneration, synovial inflammation, joint stiffness and even loss of motor function. In the clinical treatment of arthritis, conventional analgesic and anti-inflammatory drugs have great side effects. We have evaluated the possibility of the endogenous transcription regulator Ski as an anti-inflammatory alternative in OA through experimental studies in animal models and in vivo and in vitro. Male Sprague‒Dawley rats were injected with monosodium iodoacetate (MIA) into the knee joints to induce symptoms identical to those of human OA. We isolated knee synovial tissue under sterile conditions and cultured primary synovial cells. In vitro, Ski inhibits the proinflammatory factors IL-1ß, IL-6 and TNF-α mRNA and protein expression in lipopolysaccharide (LPS)-stimulated fibroblast-like synoviocytes (FLSs) and U-937 cells. In addition, Ski attenuates or inhibits OA-induced synovial inflammation by upregulating the protein expression of the anti-inflammatory factor IL-4 and downregulating the protein expression of downstream molecules related to the NF-κB inflammatory signaling pathway. In vivo, Ski downregulated proinflammatory factors and p-NF-κB p65 in KOA synovial tissue and alleviated pain-related behaviors in KOA rats. These experimental data show that Ski has strong anti-inflammatory activity. Ski is an endogenous factor, and if used in the clinical treatment of OA, the side effects are small. However, the anti-inflammatory mechanism of Ski must be further studied.

10.
J Mater Chem B ; 12(8): 2015-2027, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38304935

ABSTRACT

Insufficient antibacterial effects and over-fast degradation are the main limitations of magnesium (Mg)-based orthopedic implants. In this study, a sandwiched composite coating containing a triclosan (TCS)-loaded poly(lactic acid) (PLA) layer inside and brushite (DCPD) layer outside was prepared on the surface of the Mg-Nd-Zn-Zr (denoted as JDBM) implant. In vitro degradation tests revealed a remarkable improvement in the corrosion resistance and moderate degradation rate. The drug release profile demonstrated a controllable and sustained TCS release for at least two weeks in vitro. The antibacterial rates of the implant were all over 99.8% for S. aureus, S. epidermidis, and E. coli, demonstrating superior antibacterial effects. Additionally, this coated JDBM implant exhibited no cytotoxicity but improved cell adhesion and proliferation, indicating excellent cytocompatibility. In vivo assays were conducted by implant-related femur osteomyelitis and osseointegration models in rats. Few bacteria were attached to the implant surface and the surrounding bone tissue. Furthermore, the coated JDBM implant exhibited more new bone formation than other groups due to the synergistic biological effects of released TCS and Mg2+, revealing excellent osteogenic ability. In summary, the JDBM implant with the sandwiched composite coating could significantly enhance the antibacterial activities and osteogenic properties simultaneously by the controllable release of TCS and Mg2+, presenting great potential for clinical transformation.


Subject(s)
Magnesium , Osteogenesis , Rats , Animals , Magnesium/pharmacology , Escherichia coli , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology
11.
Muscle Nerve ; 69(2): 227-238, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38063327

ABSTRACT

INTRODUCTION/AIMS: Many small-sized, single-center preclinical studies have investigated the benefits of introducing stem cells into the interior of nerve conduit. The aims of this meta-analysis are to review and contrast the effects of various types of stem cells in in vivo models used to reconstruct peripheral nerve injuries (PNIs) and to assess the reliability and stability of the available evidence. METHODS: A systematic search was conducted using Cochrane Library, Embase, PubMed, and Web of Science to identify studies conducted from January 1, 2000, to September 21, 2022, and investigate stem cell therapy in peripheral nerve reconstruction animal models. Studies that met the relevant criteria were deemed eligible for this meta-analysis. RESULTS: Fifty-five preclinical studies with a total of 1234 animals were incorporated. Stem cells demonstrated a positive impact on peripheral nerve regeneration at different follow-up times in the forest plots of five outcome indicators: compound muscle action potential (CMAP) amplitude, latency, muscle mass ratio, nerve conduction velocity, and sciatic functional index (SFI). In most comparisons, stem cell groups showed substantial differences compared with the control groups. The superior performance of adipose-derived stem cells (ADSCs) in terms of SFI, CMAP amplitude, and latency (p < .001) was identified. DISCUSSION: The findings consistently demonstrated a favorable outcome in the reconstruction process when utilizing different groups of stem cells, as opposed to control groups where stem cells were not employed.


Subject(s)
Peripheral Nerve Injuries , Stem Cells , Animals , Nerve Regeneration/physiology , Reproducibility of Results
12.
Comput Biol Med ; 169: 107867, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38141451

ABSTRACT

As the pace of research on nanomedicine for musculoskeletal (MSK) diseases accelerates, there remains a lack of comprehensive analysis regarding the development trajectory, primary authors, and research focal points in this domain. Additionally, there's a need of detailed elucidation of potential research hotspots. The study gathered articles and reviews focusing on the utilization of nanoparticles (NPs) for MSK diseases published between 2013 and 2023, extracted from the Web of Science database. Bibliometric and visualization analyses were conducted using various tools such as VOSviewer, CiteSpace, Pajek, Scimago Graphica, and the R package. China, the USA, and India emerged as the key drivers in this research domain. Among the numerous institutions involved, Shanghai Jiao Tong University, Chinese Academy of Sciences, and Sichuan University exhibited the highest productivity levels. Vallet-Regi Maria emerged as the most prolific author in this field. International Journal of Nanomedicine accounted for the largest number of publications in this area. The top five disorders of utmost significance in this field include osteosarcoma, cartilage diseases, bone fractures, bone neoplasms, and joint diseases. These findings are instrumental in providing researchers with a comprehensive understanding of this domain and offer valuable perspectives for future investigations.


Subject(s)
Musculoskeletal Diseases , Nanoparticles , Humans , Bibliometrics
13.
Front Immunol ; 14: 1202436, 2023.
Article in English | MEDLINE | ID: mdl-37520558

ABSTRACT

Purpose: Recent scientific reports have revealed a close association between ferroptosis and the occurrence and development of osteoarthritis (OA). Nevertheless, the precise mechanisms by which ferroptosis influences OA and how to hobble OA progression by inhibiting chondrocyte ferroptosis have not yet been fully elucidated. This study aims to conduct a comprehensive systematic review (SR) to address these gaps. Methods: Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020, we conducted a comprehensive search of the Embase, Ovid, ProQuest, PubMed, Scopus, the Cochrane Library, and Web of Science databases to identify relevant studies that investigate the association between ferroptosis and chondrocytes in OA. Our search included studies published from the inception of these databases until January 31st, 2023. Only studies that met the predetermined quality criteria were included in this SR. Results: In this comprehensive SR, a total of 21 studies that met the specified criteria were considered suitable and included in the current updated synthesis. The mechanisms underlying chondrocyte ferroptosis and its association with OA progression involve various biological phenomena, including mitochondrial dysfunction, dysregulated iron metabolism, oxidative stress, and crucial signaling pathways. Conclusion: Ferroptosis in chondrocytes has opened an entirely new chapter for the investigation of OA, and targeted regulation of it is springing up as an attractive and promising therapeutic tactic for OA. Systematic review registration: https://inplasy.com/inplasy-2023-3-0044/, identifier INPLASY202330044.


Subject(s)
Ferroptosis , Osteoarthritis , Humans , Chondrocytes/metabolism , Osteoarthritis/metabolism , Oxidative Stress , Signal Transduction
14.
Front Endocrinol (Lausanne) ; 14: 1164386, 2023.
Article in English | MEDLINE | ID: mdl-37229455

ABSTRACT

Osteogenesis imperfecta (OI) is a hereditary skeletal dysplasia with an incidence of approximately 1:15,000 to 20,000. OI is usually caused by the mutation of COL1A1 and COL1A2, which would encode the α-chain of type I collagen. OI is clinically characterized by decreased bone mass, increased risk of bone fragility, blue sclerae, and dentinogenesis. Case presentation: A 29-year-old male patient was diagnosed with right tibial plateau fracture caused by slight violence. Physical examination revealed the following: height, 140 cm; weight, 70 kg; body mass index (BMI), 35.71 kg/m2; blue sclera and barrel chest were observed. X-ray examination showed left convex deformity of the thoracic vertebrae with reduced thoracic volume. Laboratory examinations revealed a decrease in both vitamin D and blood calcium levels. Bone mineral density (BMD) was lower than the normal range. After the preoperative preparation was completed, the open reduction and internal fixation of the right tibial plateau fracture were performed. Meanwhile, whole blood samples of this OI patient and the normal control were collected for RNA transcriptome sequencing. The RNA sequence analysis revealed that there were 513 differentially expressed genes (DEGs) between this OI patient and the normal control. KEGG-enriched signaling pathways were significantly enriched in extracellular matrix (ECM)-receptor interactions. Conclusion: In this case, DEGs between this OI patient and the normal control were identified by RNA transcriptome sequencing. Moreover, the possible pathogenesis of OI was also explored, which may provide new evidence for the treatment of OI.


Subject(s)
Fractures, Bone , Osteogenesis Imperfecta , Tibial Plateau Fractures , Male , Humans , Adult , Osteogenesis Imperfecta/complications , Osteogenesis Imperfecta/genetics , Osteogenesis Imperfecta/epidemiology , Mutation , Fractures, Bone/epidemiology
15.
Nat Commun ; 14(1): 3159, 2023 05 31.
Article in English | MEDLINE | ID: mdl-37258510

ABSTRACT

Intra-articular injection of therapeutics is an effective strategy for treating osteoarthritis (OA), but it is hindered by rapid drug diffusion, thereby necessitating high-frequency injections. Hence, the development of a biofunctional hydrogel for improved delivery is required. In this study, we introduce a liposome-anchored teriparatide (PTH (1-34)) incorporated into a gallic acid-grafted gelatin injectable hydrogel (GLP hydrogel). We show that the GLP hydrogel can form in situ and without affecting knee motion after intra-articular injection in mice. We demonstrate controlled, sustained release of PTH (1-34) from the GLP hydrogel. We find that the GLP hydrogel promotes ATDC5 cell proliferation and protects the IL-1ß-induced ATDC5 cells from further OA progression by regulating the PI3K/AKT signaling pathway. Further, we show that intra-articular injection of hydrogels into an OA-induced mouse model promotes glycosaminoglycans synthesis and protects the cartilage from degradation, supporting the potential of this biomaterial for OA treatment.


Subject(s)
Hydrogels , Osteoarthritis , Mice , Animals , Hydrogels/therapeutic use , Liposomes/therapeutic use , Gelatin , Teriparatide/therapeutic use , Phosphatidylinositol 3-Kinases , Osteoarthritis/drug therapy , Injections, Intra-Articular
16.
Front Immunol ; 14: 1150572, 2023.
Article in English | MEDLINE | ID: mdl-37180142

ABSTRACT

Objectives: The aim of this systematic review was to summarize the available literature on gut microbiome (GMB) and osteoarthritis (OA), analyze the correlation between GMB and OA, and explore potential underlying mechanisms. Methods: A systematic search of the PubMed, Embase, Cochrane, and Web of Science with the keywords "Gut Microbiome" and "Osteoarthritis" was conducted to identify the human and animal studies exploring the association between GMB and OA. The retrieval time range was from the database inception to July 31, 2022. Studies reported the other arthritic diseases without OA, reviews, and studies focused on the microbiome in other parts of the body with OA, such as oral or skin, were excluded. The included studies were mainly reviewed for GMB composition, OA severity, inflammatory factors, and intestinal permeability. Results: There were 31 studies published met the inclusion criteria and were analyzed, including 10 human studies and 21 animal studies. Human and animal studies have reached a consistent conclusion that GMB dysbiosis could aggravate OA. In addition, several studies have found that alterations of GMB composition can increase intestinal permeability and serum levels of inflammatory factors, while regulating GMB can alleviate the changes. Owing to the susceptibility of GMB to internal and external environments, genetics, and geography, the included studies were not consistent in GMB composition analysis. Conclusion: There is a lack of high-quality studies evaluating the effects of GMB on OA. Available evidence indicated that GMB dysbiosis aggravated OA through activating the immune response and subsequent induction of inflammation. Future studies should focus on more prospective, cohort studies combined with multi-omics to further clarify the correlation.


Subject(s)
Gastrointestinal Microbiome , Osteoarthritis , Animals , Humans , Dysbiosis , Prospective Studies , Inflammation
18.
Eur J Pharmacol ; 950: 175753, 2023 Jul 05.
Article in English | MEDLINE | ID: mdl-37119958

ABSTRACT

Osteoporosis is a common disease in elderly individuals, and osteoporosis can easily lead to bone and hip fractures that seriously endanger the health of elderly individuals. At present, the treatment of osteoporosis is mainly anti-osteoporosis drugs, but there are side effects associated with anti-osteoporosis drugs. Therefore, it is very important to develop early diagnostic indicators and new therapeutic drugs for the prevention and treatment of osteoporosis. Long noncoding RNAs (lncRNAs), noncoding RNAs longer than 200 nucleotides, can be used as diagnostic markers for osteoporosis, and lncRNAs play an important role in the progression of osteoporosis. Many studies have shown that lncRNAs can be the target of osteoporosis. Therefore, herein, the role of lncRNAs in osteoporosis is summarized, aiming to provide some information for the prevention and treatment of osteoporosis.


Subject(s)
Osteoporosis , RNA, Long Noncoding , Humans , Aged , RNA, Long Noncoding/genetics , Osteoporosis/drug therapy , Osteoporosis/genetics , RNA, Untranslated , Bone and Bones
19.
Sensors (Basel) ; 23(4)2023 Feb 13.
Article in English | MEDLINE | ID: mdl-36850691

ABSTRACT

At present, some studies have combined federated learning with blockchain, so that participants can conduct federated learning tasks under decentralized conditions, sharing and aggregating model parameters. However, these schemes do not take into account the trusted supervision of federated learning and the case of malicious node attacks. This paper introduces the concept of a trusted computing sandbox to solve this problem. A federated learning multi-task scheduling mechanism based on a trusted computing sandbox is designed and a decentralized trusted computing sandbox composed of computing resources provided by each participant is constructed as a state channel. The training process of the model is carried out in the channel and the malicious behavior is supervised by the smart contract, ensuring the data privacy of the participant node and the reliability of the calculation during the training process. In addition, considering the resource heterogeneity of participant nodes, the deep reinforcement learning method was used in this paper to solve the resource scheduling optimization problem in the process of constructing the state channel. The proposed algorithm aims to minimize the completion time of the system and improve the efficiency of the system while meeting the requirements of tasks on service quality as much as possible. Experimental results show that the proposed algorithm has better performance than the traditional heuristic algorithm and meta-heuristic algorithm.

20.
Front Genet ; 14: 1101683, 2023.
Article in English | MEDLINE | ID: mdl-36816047

ABSTRACT

Background: Increasing evidence indicates a crucial role for N7-methylguanosine (m7G) methylation modification in human disease development, particularly cancer, and aberrant m7G levels are closely associated with tumorigenesis and progression via regulation of the expression of multiple oncogenes and tumor suppressor genes. However, the role of m7G in sarcomas (SARC) has not been adequately evaluated. Materials and methods: Transcriptome and clinical data were gathered from the TCGA database for this study. Normal and SARC groups were compared for the expression of m7G-related genes (m7GRGs). The expression of m7GRGs was verified using real-time quantitative PCR (RT-qPCR) in SARC cell lines. Then, differentially expressed genes (DEGs) were identified between high and low m7GRGs expression groups in SARC samples, and GO enrichment and KEGG pathways were evaluated. Next, prognostic values of m7GRGs were evaluated by Cox regression analysis. Subsequently, a prognostic model was constructed using m7GRGs with good prognostic values by Lasso regression analysis. Besides, the relationships between prognostic m7GRGs and immune infiltration, clinical features, cuproptosis-related genes, and antitumor drugs were investigated in patients with SARC. Finally, a ceRNA regulatory network based on m7GRGs was constructed. Results: The expression of ten m7GRGs was higher in the SARC group than in the control group. DEGs across groups with high and low m7GRGs expression were enriched for adhesion sites and cGMP-PKG. Besides, we constructed a prognostic model that consists of EIF4A1, EIF4G3, NCBP1, and WDR4 m7GRGs for predicting the survival likelihood of sarcoma patients. And the elevated expression of these four prognostic m7GRGs was substantially associated with poor prognosis and elevated expression in SARC cell lines. Moreover, we discovered that these four m7GRGs expressions were negatively correlated with CD4+ T cell levels, dendritic cell level and tumor purity, and positively correlated with tumor mutational burden, microsatellite instability, drug sensitivity and cuproptosis-related genes in patients with sarcomas. Then, a triple regulatory network of mRNA, miRNA, and lncRNA was established. Conclusion: The current study identified EIF4A1, EIF4G3, NCBP1, and WDR4 as prognostic genes for SARC that are associated with m7G.These findings extend our knowledge of m7G methylation in SARC and may guide the development of innovative treatment options.

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