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BACKGROUND: Synovitis, characterized by inflammation of the synovial membrane, is commonly induced by meniscus tears. However, significant differences in inflammatory responses and the key inflammatory mediators of synovium induced by different types of meniscal tears remain unclear. METHODS: Magnetic resonance imaging (MRI) was employed to identify the type of meniscus tear, and the quantification of synovial inflammation was assessed through H&E staining assay. Transcription and expression levels of IL-1ß and IL-6 were evaluated using bioinformatics, ELISA, RT-qPCR, and IHC of CD68 staining assays. The therapeutic potential of Docosapentaenoic Acid (DPA) was determined through network pharmacology, ELISA, and RT-qPCR assays. The safety of DPA was assessed using colony formation and EdU staining assays. RESULTS: The results indicate that both IL-1ß and IL-6 play pivotal roles in synovitis pathogenesis, with distinct expression levels across various subtypes. Among tested meniscus tears, oblique tear and bucket handle tear induced the most severe inflammation, followed by radial tear and longitudinal tear, while horizontal tear resulted in the least inflammation. Furthermore, in synovial inflammation induced by specific meniscus tears, the anterior medial tissues exhibited significantly higher local inflammation than the anterior lateral and suprapatellar regions, highlighting the clinical relevance and practical guidance of anterior medial tissues' inflammatory levels. Additionally, we identified the essential omega-3 fatty acid DPA as a potential therapeutic agent for synovitis, demonstrating efficacy in blocking the transcription and expression of IL-1ß and IL-6 with minimal side effects. CONCLUSION: These findings provide valuable insights into the nuanced nature of synovial inflammation induced by various meniscal tear classifications and contribute to the development of new adjunctive therapeutic agents in the management of synovitis.
Assuntos
Ácidos Graxos Insaturados , Interleucina-1beta , Imageamento por Ressonância Magnética , Membrana Sinovial , Sinovite , Lesões do Menisco Tibial , Lesões do Menisco Tibial/tratamento farmacológico , Lesões do Menisco Tibial/metabolismo , Sinovite/tratamento farmacológico , Sinovite/metabolismo , Sinovite/patologia , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Humanos , Ácidos Graxos Insaturados/farmacologia , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/uso terapêutico , Masculino , Interleucina-1beta/metabolismo , Animais , Interleucina-6/metabolismo , Feminino , Meniscos Tibiais/efeitos dos fármacos , Meniscos Tibiais/metabolismo , Camundongos , Modelos Animais de DoençasRESUMO
Paeoniflorin is a glycoside compound found in Paeonia lactiflora Pall that is used in traditional herbal medicine and shows various protective effects on the cardio-cerebral vascular system. It has been reported that the pharmacological effects of paeoniflorin might be generated by its metabolites. However, the bioavailability of paeoniflorin by oral administration is low, which greatly limits its clinical application. In this paper, a paeoniflorin-converting enzyme gene (G6046, GenBank accession numbers: OP856858) from Cunninghamella blakesleeana (AS 3.970) was identified by comparative analysis between MS analysis and transcriptomics. The expression, purification, enzyme activity, and structure of the conversion products produced by this paeoniflorin-converting enzyme were studied. The optimal conditions for the enzymatic activity were found to be pH 9, 45 °C, resulting in a specific enzyme activity of 14.56 U/mg. The products were separated and purified by high-performance counter-current chromatography (HPCCC). Two main components were isolated and identified, 2-amino-2-p-hydroxymethyl-methyl alcohol-benzoate (tirs-benzoate) and 1-benzoyloxy-2,3-propanediol (1-benzoyloxypropane-2,3-diol), via UPLC-Q-TOF-MS and NMR. Additionally, paeoniflorin demonstrated the ability to metabolize into benzoic acid via G6046 enzyme, which might exert antidepressant effects through the blood-brain barrier into the brain.
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Cunninghamella , Paeonia , Glucosídeos/metabolismo , Glicosídeos/metabolismo , Cunninghamella/metabolismo , Monoterpenos/química , Benzoatos/metabolismo , Paeonia/químicaRESUMO
PURPOSE: Treatment algorithms may consider many factors like glenoid and humeral bone loss, or scores such as the instability severity index score (ISIS). As most studies only evaluate a part of these factors, there is still no evidence-based consensus estalished. Our study aims to summarize the surgical options for treatment of glenoid bone loss (GBL) in anterior shoulder instability. METHODS: Based on the current available literature, surgical options including Bankart repair and glenoid bone augmentation should be considered while taking into consideration the degree of bone loss which has been divided into < 10%, 10-20% and > 20%. RESULTS: There are many new techniques evolving including arthroscopic anatomic glenoid reconstruction with bone blocks. CONCLUSION: Future long-term outcome studies and randomized controlled trials comparing established techniques will be needed for new evidence-based treatment algorithms.
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This study aimed to compare the nutritive value and obesity prevention of ordinary Cordyceps militaris (CM) and selenium-enriched CM (SeCM). The results indicated that Se enrichment significantly increased the total carbohydrate and soluble dietary fiber content, while the protein and insoluble dietary fiber content decreased. Although the fat content was not affected, the medium and long-chain fatty acids content significantly changed. Moreover, Se enrichment significantly elevated the secondary metabolites belonging to terpenoids and alkaloids, which are linked with the enhanced biosynthesis of secondary metabolites. Both CM and SeCM reduced body weight, adipose accumulation, impaired glucose tolerance, and lipid levels in high-fat diet (HFD)-fed mice, and there was no significant difference between them. Network pharmacological analysis revealed that dietary CM and SeCM prevented HFD-induced obesity and associated metabolic diseases with multi-ingredients acting on multi-targets. Overall, Se enrichment improved the nutritive value of CM without altering its role in preventing obesity.
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Objective: Osteochondral decellularization can promote local vascular regeneration, but the exact mechanism is unknown. The aim of this study is to study osteogenic microvascular regeneration in single cells. Methods: The scRNA-seq dataset of human periosteal-derived cells (hPDCs) were analyzed by pySCENIC. To examine the role of TBX3 in osteogenesis and vascularization, cell transfection, qRT-PCR, western blot, and CCK-8 cell proliferation assays were performed. Results: TCF7L2, TBX3, FLI1, NFKB2, and EZH2 were found to be transcription factors (TFs) most closely associated with corresponding cells. The regulatory network of these TFs was then visualized. Our study knocked down the expression of TBX3 in human osteoblast cell lines. In the TBX3 knockdown group, we observed decreased expression of VEGFA, VEGFB, and VEGFC. Moreover, Western blot analysis showed that downregulating TBX3 resulted in a reduction of VEGFA expression. And TBX3 stimulated osteoblast proliferation in CCK-8 assays. Conclusion: TBX3 regulates VEGFA expression and promotes osteoblast proliferation in skeletal microvasculature formation. The findings provide a theoretical basis for investigating the role of TBX3 in promoting local vascular regeneration.
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Osteoblastos , Sincalida , Humanos , Diferenciação Celular/fisiologia , Sincalida/metabolismo , Proliferação de Células/genética , Regeneração/genética , Fator A de Crescimento do Endotélio Vascular/genética , Proteínas com Domínio T/metabolismoRESUMO
Objective: Although emerging evidence suggests that both osteoarthritis (OA) and brain atrophy (as assessed by structural neuroimaging markers) are associated with the risk of dementia, little is known about the association between OA and structural neuroimaging markers. This study aimed to examine the association of OA with changes in structural neuroimaging markers among non-demented older people. Methods: We examined the cross-sectional and longitudinal associations between OA and structural neuroimaging markers (hippocampal volume, entorhinal volume, ventricular volume, and volume of gray matter of the whole brain) among non-demented older people. We categorized our participants as those without OA (OA-) and those with OA (OA+). At baseline, we included 1,281 non-demented older adults, including 1,050 without OA and 231 with OA. Results: In the cross-sectional analysis, we did not observe any significant difference in structural neuroimaging markers between the two OA groups. In the longitudinal analysis, we found that compared to participants without OA, those with OA showed a steeper decline in volumes of the gray matter of the whole brain among non-demented older adults. Conclusions: OA was associated with a steeper decline in volumes of the gray matter of the whole brain over time among non-demented older people.
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Critical-sized bone defects are incapable of self-healing and are commonly seen in clinical practice. The authors explore a new treatment for this, decellularized periosteum is applied to chitosan globules (chitosan-DP globules) as a hybrid material. The efficacy of chitosan-DP globules on rabbit femoral condyle bone defects is assessed with biocompatibility, biomechanics, and osteogenic efficiency measurements, and compared with the results of chitosan globules and empty control. No difference in cytotoxicity is observed among chitosan-DP globules, chitosan globules, and the empty control. Chitosan-DP globules possesse a better surface for cell adhesion than did chitosan globules. Chitosan-DP globules demonstrate superior efficiency for osteogenesis in the defect area compared to chitosan globules as per microcomputed tomography examination and push-out testing, with relatively minor histological differences. Both chitosan globule groups show more satisfactory results than those for the empty control. The results implicate chitosan-DP globules as a promising solution for bone defects.
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Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Quitosana/farmacologia , Fêmur/patologia , Periósteo , Animais , Materiais Biocompatíveis/química , Fenômenos Biomecânicos , Regeneração Óssea/fisiologia , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Quitosana/farmacocinética , Fêmur/lesões , Células-Tronco Mesenquimais/efeitos dos fármacos , Peso Molecular , Coelhos , Propriedades de Superfície , Microtomografia por Raio-XRESUMO
Osteonecrosis of the femoral head(ONFH), a refractory disease characterized by death of the osteocytes and the bone marrow due to inadequate blood supply caused by various mechanisms, usually leads to the collapse of the femoral head and malfunction of the hip joint. The crux is to diagnose ONFH early in the precollapse stage and prevent subsequent progression of collapsing through early interventions, thus delaying or avoiding the replacement of the hip joint. A number of joint salvaging operation treatments for early stage ONFH are available. However, there has been no consensus with regard to the ideal treatment. The main trend now is to unite core decompression with bone-grafting, tantalum rod, bone marrow mesenchymal stem cell (BMSC) and other treatments. Also there are ways of osteotomy altering the angle of the femoral neck to relocate necrotic tissue from the weight-bearing segment. The implanting of tantalum rod remains controversial and the advent of bone marrow mesenchymal stem cell (BMSC) holds huge potential.
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Necrose da Cabeça do Fêmur/diagnóstico , Necrose da Cabeça do Fêmur/prevenção & controle , Terapia de Salvação/métodos , Transplante Ósseo , Descompressão Cirúrgica , Progressão da Doença , Colo do Fêmur , Humanos , Transplante de Células-Tronco Mesenquimais , TantálioRESUMO
Bone grafting or bone substitute is typically used to bridge a bone defect that has been caused by trauma, tumor resection, pathological degeneration, or congenital deformations. However, bone graft healing and remodeling is always a major concern of orthopedic surgeons. Because the periosteum has a remarkable regenerative capacity and is widely recognized to be essential for the initiation of bone graft healing and remodeling, the present study aimed to produce a rabbit decellularized periosteum (D-periosteum) to be used as a biologic scaffold for future bone tissue engineering. We obtained the D-periosteum by employing a combination of commonly used decellularization processes, which include physical methods as well as chemical and enzymatic solutions. The cellular components were effectively removed, and this removal was demonstrated using current decellularization criteria (H&E staining, DAPI staining, DNA quantification and agarose gel electrophoresis); however, there were no significant alterations of the native extracellular matrix (ECM) properties (collagen, glycosaminoglycan (GAG), microarchitecture and mechanical properties). Periosteum-derived cells (PDCs) could adhere, proliferate and infiltrate into the D-periosteum in vitro. The allogenic D-periosteum was implanted subcutaneously into the backs of rabbits over 28 days to study the biocompatibility in vivo. The D-periosteum did not elicit a severe immunogenic response. In summary, a biologic scaffold composed of ECM from periosteum has been successfully developed. The D-periosteum maintains biocompatibility in vitro and in vivo and, therefore, can provide a naturally compatible scaffold for use in future bone tissue engineering.