Knee osteoarthritis and aging: evaluation of the different muscles of thigh / Artrosis de rodilla y envejecimiento: investigación de los diferentes músculos del muslo / Osteoartrite de joelho e envelhecimento: investigação de diferentes músculos da coxa

ABSTRACT Introduction: Osteoarthritis (OA) is a chronic inflammatory degenerative disease, characterized by progressive degeneration of the articular cartilage, affecting mostly the knee joint. The elderly population is the most affected, intensifying the aging process. The concentration of intramuscular adipose tissue in the thigh muscles and knee OA at different ages remains under investigation. Objective: Investigate the cross-sectional area of thigh muscles at different ages with the relationship of the presence of intramuscular fat and knee OA. Methods: 80 participants were paired into 4 groups: Young Osteoarthritis Group and Old Osteoarthritis Group, both sedentary with knee OA diagnosis II or III; Healthy Young Group and Healthy Old Group, both healthy and sedentary. The groups were paired according to gender and body mass index, submitted to physiotherapeutic evaluation, WOMAC questionnaire, knee X-ray and thigh CT scans. Morphometric analysis was performed manually with ITK-SNAP software (version 3.6), by a single evaluator. Statistical analysis used the one-way ANOVA test followed by Bonferroni post-hoc for dependent variables (p≤0.05). Results: Comparison of the cross-sectional area of the rectus femoris, vastus lateralis, semitendinosus, sartorius and gracilis muscles between the groups indicated no significant differences (p>0.05). The study of attenuation for muscle adipose tissue indicated no significant difference in the values of between the OA-Young and Aged-S groups for all the muscles evaluated. Conclusion: Young individuals with knee OA present muscle morphological characteristics similar to those found during the aging process, characterizing early aging of the thigh muscles. Level of Evidence III; Retrospective cross-sectional and observational study.

RESUMEN Introducción: La artrosis (OA) es una enfermedad inflamatoria degenerativa crónica, caracterizada por la degeneración progresiva del cartílago articular, que afecta principalmente a la articulación de la rodilla. La población anciana es la más afectada, intensificándose el proceso de envejecimiento. La concentración de tejido adiposo intramuscular en los músculos del muslo y la OA de rodilla a diferentes edades sigue siendo objeto de investigación. Objetivo: Investigar el área transversal de los músculos del muslo a diferentes edades con la relación de la presencia de grasa intramuscular y la OA de rodilla. Métodos: Se emparejó a 80 participantes en 4 grupos: Grupo de jóvenes con osteoartritis y Grupo de mayores con osteoartritis, ambos sedentarios y con diagnóstico de OA de rodilla II o III; Grupo de jóvenes sanos y Grupo de mayores sanos, ambos sanos y sedentarios. Los grupos fueron emparejados según sexo e índice de masa corporal, sometidos a evaluación fisioterapéutica, cuestionario WOMAC, exámenes radiográficos de las rodillas y tomografía computarizada del muslo. El análisis morfométrico se realizó manualmente con el software ITK-SNAP (versión 3.6), por un único evaluador. En el análisis estadístico se utilizó la prueba ANOVA unidireccional seguida del post-hoc de Bonferroni para las variables dependientes (p≤0,05). Resultados: La comparación del área transversal de los músculos recto femoral, vasto lateral, semitendinoso, sartorio y gracilis entre los grupos no indicó diferencias significativas (p>0,05). El estudio de la atenuación para el tejido adiposo muscular no indicó diferencias significativas en los valores de entre los grupos OA-Young y Aged-S para todos los músculos evaluados. Conclusión: Individuos jóvenes con OA de rodilla presentan características morfológicas musculares similares a las encontradas durante el proceso de envejecimiento, caracterizando el envejecimiento precoz de los músculos del muslo. Nivel de Evidencia III; Estudio transversal y observacional retrospectivo.

RESUMO Introdução: A osteoartrite (OA) é uma doença inflamatória crônico-degenerativa, caracterizada pela degeneração progressiva da cartilagem articular, acometendo em maior parte a articulação do joelho. A população idosa é a mais atingida, intensificando o processo de envelhecimento. A concentração de tecido adiposo intramuscular nos músculos da coxa e a OA de joelho em diferentes idades permanece em investigação. Objetivo: Investigar a área de secção transversa dos músculos da coxa em diferentes idades com a relação da presença de gordura intramuscular e OA de joelho. Métodos: 80 participantes foram pareados em 4 grupos: Grupo Osteoartrite Jovem e Grupo Osteoartrite Idoso, ambos sedentários com diagnóstico de OA de joelho II ou III; Grupo Jovem Saudável e Grupo Idoso Saudável, ambos saudáveis e sedentários. Os grupos foram pareados de acordo com sexo e índice de massa corporal, submetidos à avaliação fisioterapêutica, questionário WOMAC, exames de raio-x dos joelhos e tomografia computadorizada da coxa. A análise morfométrica foi realizada manualmente com software ITK-SNAP (versão 3.6), por um único avaliador. Análise estatística utilizou o teste ANOVA one-way seguido pelo post-hoc de Bonferroni, para variáveis dependentes (p≤0,05). Resultados: A comparação da área de secção transversa dos músculos reto femoral, vasto lateral, semitendinoso, sartório e grácil, entre os grupos, não indicou diferenças significativas (p>0,05). O estudo da atenuação para o tecido adiposo muscular não indicou diferença significativa nos valores de entre os grupos OA-Jovem e Idoso-S para todos os músculos avaliados. Conclusão: Indivíduos jovens com OA de joelho apresentam características morfológicas musculares semelhantes às encontradas durante o processo de envelhecimento, caracterizando um envelhecimento precoce dos músculos da coxa.Nível de Evidência III; Estudo retrospectivo transversal e observacional.

Comparison between 200 mg generic celecoxib hard capsules and Celebra®: bioequivalence study in healthy male and female subjects under fasting conditions after a single dose / Comparação entre celecoxibe genérico de 200 mg em cápsulas duras e Celebra®: estudo de bioequivalência em indivíduos saudáveis do sexo masculino e feminino, em jejum, após uma dose única

ABSTRACT BACKGROUND AND OBJECTIVES: The objective of this study was to assess the bioequivalence between two 200 mg celecoxib hard capsule formulations administered to healthy male and female participants under fasting conditions with the aim of providing an alternative pharmaceutical product to the reference drug, Celebra®. METHODS: A randomized, open label, single dose, 2x2 crossover trial was conducted with 60 adult healthy subjects under fasting conditions comparing single doses of two celecoxib hard capsules formulation. Pharmacokinetic parameters were calculated following the determination of drugs concentrations in human plasma using a validated liquid chromatography with a tandem mass spectrometer detector method (LC-MS/MS). RESULTS: Statistical analysis provided geometric mean of test/reference ratio, confidence intervals, intra-subject variation coefficient and power of the test to the pharmacokinetic parameters Cmax, AUC0-t, and AUC0-∞. Confidence intervals for the geometric mean (90% CI) of the test/reference drugs for celecoxib were 98.26 to 122.75% for Cmax, 100.27% to 110.78% for AUC0-t, and 96.87% to 110.29% for AUC0-∞. The power of the test found was 95.09% for Cmax, 100.00% for AUC0-t, and 99.99% for AUC0-∞. CONCLUSION: The formulations met the Brazilian standards for interchangeability, as the confidence intervals for Cmax and AUC0-t ratios are within the range of 80% to 125%, thus meeting the requirements of the legislation during market registration. The researched product was approved by the regulatory authorities and became a commercially competitive option to the reference product for the Brazilian population.

RESUMO JUSTIFICATIVA E OBJETIVOS: O objetivo deste estudo foi avaliar a bioequivalência entre duas formulações de cápsulas duras de celecoxibe de 200 mg administradas a participantes saudáveis do sexo masculino e feminino em condições de jejum com o objetivo de fornecer um produto farmacêutico alternativo ao fármaco de referência, Celebra®. MÉTODOS: Estudo randomizado, aberto, de dose única e cruzado 2x2. Foi conduzido com 60 indivíduos adultos saudáveis em condições de jejum, comparando doses únicas de duas formulações de cápsulas duras de celecoxibe. Os parâmetros farmacocinéticos foram calculados após a determinação das concentrações dos fármacos no plasma humano usando uma cromatografia líquida validada com um método detector de espectrômetro de massa em tandem (LC-MS/MS). RESULTADOS: A análise estatística forneceu a média geométrica da razão teste/referência, os intervalos de confiança, o coeficiente de variação intra-sujeito e o poder do teste para os parâmetros farmacocinéticos Cmáx, AUC0-t e AUC0-∞. Os intervalos de confiança para a média geométrica (IC 90%) dos fármacos teste/referência para o celecoxibe foram 98,26 a 122,75% para Cmáx, 100,27% a 110,78% para AUC0-t e 96,87% a 110,29% para AUC0-∞. O poder do teste encontrado foi de 95,09% para Cmáx, 100,00% para AUC0-t e 99,99% para AUC0-∞. CONCLUSÃO: As formulações atenderam aos padrões brasileiros de intercambialidade, pois os intervalos de confiança para as razões Cmáx e AUC0-t estão dentro da faixa de 80% a 125%, atendendo, assim, às exigências da legislação para o registro no mercado. O produto pesquisado foi aprovado pelas autoridades regulatórias e tornou-se uma opção comercialmente competitiva ao produto de referência para a população brasileira.

Effect of Dioscorea villosa extract and the phytoestrogen diosgenin on ovariectomized mice with zymosan-induced arthritis

Abstract Humans are exposed to natural compounds such as phytoestrogens primarily through diet and supplements. These compounds promote health by alleviating the symptoms and illnesses associated with menopause and arthritis. Diosgenin (DSG) occurs naturally in plants such as Dioscorea villosa (DV) and binds to estrogen receptors, so it may have similar effects to this hormone, including against arthritis. Thus, we investigated the effect of chronic treatment with dry extract of DV and its phytoestrogen DSG on ovariectomized mice with arthritis. We found that dry extract of Dioscorea villosa (DV) contains the phytoestrogen diosgenin (DSG) in its composition. Furthermore, arthritic mice treated with DV and DSG showed reduced neutrophil accumulation in the articular cartilage. Also, the dry extract of DV administered orally (v.o) did not alter the leukocyte count in the joints or promote changes in the reproductive tract. However, DSG altered these parameters, with possible beneficial effects by reducing symptoms related to reproductive aging. Thus, oral treatment with dry extract of DV and subcutaneous (s.c) treatment with DSG showed promise by acting against inflammation caused by arthritis and reducing symptoms in the reproductive tract due to menopause.

Effects of low-level laser therapy on acupuncture points on knee pain and function in knee osteoarthritis

SUMMARY OBJECTIVE: Knee osteoarthritis is a common and disabling disease. We aimed to examine the effect of low-level laser therapy in addition to routine physical therapy modalities (transcutaneous electrical stimulation, superficial heating modality of infrared, ultrasound, and exercise) on the functional status and pain in knee osteoarthritis. METHODS: Patients with knee osteoarthritis (n=71) who underwent physical therapy (transcutaneous electrical stimulation, infrared, ultrasound, exercise therapy, and low-level laser therapy) were retrospectively screened. Patients who received low-level laser therapy on acupuncture points, transcutaneous electrical stimulation, infrared, ultrasound, and exercise were included in the low-level laser therapy (+) (n=35), and patients who received only transcutaneous electrical stimulation, ultrasound, infrared, and exercise were included in the low-level laser therapy (-) group (n=36). The Visual Analog Scale for activity pain, Lysholm Knee Scoring Scale, and walking and stair climbing tests were used before and after treatment obtained from patient files. RESULTS: The post-treatment Visual Analog Scale activity score and walking and stair climbing test results were statistically significantly lower in the low-level laser therapy (+) group than in the low-level laser therapy (-) group. There was no significant difference in post-treatment Lysholm Knee Scoring Scale scores between the two groups. In both groups, the Visual Analog Scale activity, Lysholm Knee Scoring Scale, and walking and stair climbing test scores statistically significantly decreased after treatment. CONCLUSION: Knee osteoarthritis increases with aging and creates significant functional limitations. low-level laser therapy with routine physiotherapy contributed to the improvement in the pain and functional status of the patients with knee osteoarthritis. Low-level laser therapy can be recommended in osteoarthritis treatment guidelines with the support of further studies, which is an easy-to-apply, effective, and reliable method.

Bone protective effect of sinomenine against monosodium iodoacetate induced knee and hip injury in rat model: an inflammatory pathway

Purpose: Osteoarthritis (OA) is a degenerative joint disease which is categorized via destruction of joint cartilage and it also affects the various joints, especially knees and hips. Sinomenine active phytoconstituents isolated from the stem of Sinomenium acutum and already proof anti-inflammatory effect against the arthritis model of rodent. In this experimental protocol, we scrutinized the anti-osteoarthritis effect of sinomenine against monosodium iodoacetate (MIA) induced OA in rats. Methods: MIA (3 mg/50 µL) was used for inducing the OA in the rats, and rats received the oral administration of sinomenine (2.5, 5 and 7.5 mg/kg body weight) up to the end of the experimental study (four weeks). The body and organs weight were estimated. Aggrecan, C-terminal cross-linked telopeptide of type II collagen (CTX-II), glycosaminoglycans (GCGs), monocyte chemoattractant protein-1 (MCP-1), Interferon gamma (IFN-γ), antioxidant, inflammatory cytokines, inflammatory mediators and matrix metalloproteinases (MMP) were analyzed. Results: Sinomenine significantly (P < 0.001) boosted the body weight and reduced the heart weight, but the weight of spleen and kidney remain unchanged. Sinomenine significantly (P < 0.001) reduced the level of nitric oxide, MCP-1 and improved the level of aggrecan, IFN-γ and GCGs. Sinomenine remarkably upregulated the level of glutathione, superoxide dismutase and suppressed the level of malonaldehyde. It effectually modulated the level of inflammatory cytokines and inflammatory mediators and significantly (P < 0.001) reduced the level of MMPs, like MMP-1, 2, 3, 9 and 13. Conclusions: Sinomenine is a beneficial active agent for the treatment of OA disease.

Clinical and functional evaluation of wrists and hands of spinal cord injured patients / Avaliação clínica e funcional de mãos e punhos de pacientes lesados medulares

ABSTRACT Introduction: The inability of the spinal cord to propagate sensory and motor stimuli as a result of the disruption of the nerve tracts is called spinal cord injury. Objective: This study analyzes clinically and radiologically the hands and wrists of spinal cord injured patients, evaluating their motor and sensitive functionality, in order to determine if these patients are more likely to develop degenerative alterations. Methods: 14 patients (8 paraplegics and 6 tetraplegics) were evaluated, undergoing anamnesis and clinical examination - a scale of muscular strength (MRC - Medical Research Council) and the amplitude measurement of the movement with a manual goniometer (ROM), were used for objective evaluation - and x-ray exams. The results were compared with pre-existing data from other studies. Results: When asked, only one of the 14 observed patients complained about constant wrist pain, described as level 3 (weak to moderate), based on the visual analog scale (VAS). The motor evaluation, MRC and ROM divided the group of patients into two subgroups: paraplegic and tetraplegic patients. The x-ray analysis showed, based on Kellgren and Lawrence classification, that all exam images fit grades 1 or 2 of osteoarthritis and osteoarthrosis. Conclusion: In conclusion, spinal cord injured patients showed none or minimal clinical and radiological signs of osteoarthritis on hands or wrists. Overall, the hands and wrists of spinal cord-injured patients behave similarly to noninjured patients. Level of Evidence III; Retrospective Comparative Study.

RESUMO Introdução: A incapacidade da medula espinhal de propagar estímulos sensoriais e motores como resultado do rompimento das vias nervosas é chamada de lesão da medula espinhal. Objetivo: Este estudo analisa clínica e radiograficamente mão e punhos de pacientes lesados medulares, avaliando função motora e sensitiva, a fim de determinar se estes pacientes estariam mais propensos a alterações degenerativas. Métodos: 14 pacientes (8 paraplégicos e 6 tetraplégicos) foram avaliados, passando por anamnese e exame clínico - sendo escala de força muscular (MRC - Medical Research Council) e a medição da amplitude de movimento com um goniômetro manual (ROM) foram utilizados para análise objetiva - e radiografias. Os dados obtidos foram comparados com literatura preexistente. Resultados: Quando questionados, apenas um dos 14 pacientes observados referiu dor crônica nos punhos, descrita como nível 3 (fraca a moderada), baseada na escala visual analógica. A avaliação motora, MRC e ROM dividiram os pacientes em 2 subgrupos: pacientes paraplégicos e tetraplégicos. A análise radiográfica mostrou, baseada na classificação de Kellgren e Lawrence, que todas as imagens se encaixam nos graus 1 ou 2 de osteoartrite e osteoartrose. Conclusão: Conclui-se, então, que pacientes lesados medulares apresentam nenhuma ou mínimas alterações clínicas e radiológicas para osteoartrite ou osteoartrose de punhos ou mãos. Ou seja, no geral, mãos e punhos de pacientes lesados medulares comportam-se como os pacientes sem lesão medular. Nível de Evidência III; Estudo Retrospectivo Comparativo.

Role of Interleukin-17 family cytokines in disease severity of patients with knee osteoarthritis

Abstract Background Interleukin-17 (IL-17) family plays a role in the pathogenesis of knee osteoarthritis (KOA) by contributing to the inflammatory and destructive processes in the affected joint. This study aimed to measure levels of IL-17 A and IL-25 (IL-17E) in serum of KOA patients and determine their roles in the disease severity of patients. Methods In this, 34 patients with KOA and 30 age and sex-matched healthy subjects (HS) were enrolled. Patients were categorized based on their Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS), and Body Mass Index (BMI) scores. The enzyme-linked immunosorbent assay (ELISA) technique was employed to measure serum levels of IL-17 A and IL-25. Results Level of IL-25 was significantly higher (P < 0.0001) in the KOA subjects than HS. IL-17 A level was significantly higher in KOA cases with WOMAC < 40 (P < 0.0001) in comparison to HS. IL-25 level was significantly higher in the KOA cases with WOMAC < 40 (P < 0.0001) and with WOMAC ≥ 40 (P < 0.0001) compared to HS. IL-17 A concentration was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) compared to HS. IL-25 level was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) and with VAS ≥ 5 (P < 0.0001) in comparison to HS. KOA patients with BMI ≥ 30 had significantly higher IL-17 A and IL-25 concentration in comparison to HS. Conclusions The serum level of IL-25 in KOA patients is increased probably due to negative controlling feedback on inflammatory responses, which can be associated with obesity and disease activity.

Genetic polymorphism of WNT9A is functionally associated with thumb osteoarthritis in the Chinese population

Abstract Background In a recent genome-wide association study, novel genetic variations of WNT9A were reported to be involved in the etiopathogenesis of thumb osteoarthritis (TOA) in Caucasians. Our purposes were to replicate the association of WNT9A with the development of TOA in the Chinese population and to further unveil the functional role of the risk variants. Methods SNP rs11588850 of WNT9A were genotyped in 953 TOA patients and 1124 healthy controls. The differences of genotype and allele distributions between the patients and healthy controls were evaluated using the Chi-square test. Luciferase Reporter Assay was performed to investigate the influence of variant on the gene expression. Results There was significantly lower frequency of genotype AA in TOA patients than in the controls 74.9% vs. 81.9%, p < 0.001). The frequency of allele A was remarkably lower in the patients than in the controls (86.3% vs. 90.5%, p < 0.001), with an odds ratio of 0.66 (95% CI = 0.54-0.80). Luciferase Reporter Assay showed that the construct containing mutant allele G of rs11588850 displayed 29.1% higher enhancer activity than the wild allele A construct (p < 0.05). Conclusions Allele G of rs11588850 was associated with the increased risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA. Key Points Genetic variants of WNT9A were associated with the incidence and severity of TOA. Allele G of rs11588850 was associated with an increased transcriptional activity of WNT9A promoter. Allele G of rs11588850 may add to the risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA.

Avaliação clínica e laboratorial de cão com osteoartrose tratado com formulação de meloxicam em spray oral. Relato de caso / Clinical and laboratory evaluation of a dog with osteoarthritis treated with oral spray meloxicam formulation. Case report / Avaliación clínica y de laboratorio de un perro con osteoartrosis tratado con formulación de meloxicam en spray oral. Reporte de caso

O presente relato de caso avaliou o meloxicam solução oral spray com o sistema de absorção transmucosa no tratamento de um cão tripedal acometido por osteoartrose em joelho e coluna. Além da avaliação ortopédica, foram realizados questionários de avaliação de dor, baropodometria, termografia e monitoramento de atividade.

The present case report evaluated the meloxicam oral solution spray with the transmucosal absorption system in the treatment of a three-legged dog affected by osteoarthritis in the knee and spine. In addition to the orthopedic evaluation, assessments of pain, baropodometry, thermography, and activity monitoring were carried out.

El presente informe de caso evaluó el spray de solución oral de meloxicam con el sistema de absorción transmucosa en el tratamiento de un perro de tres patas afectado por osteoartritis en la rodilla y columna. Además de la evaluación ortopédica, se realizaron cuestionarios de evaluación del dolor, baropodometría, termografía y monitoreo de la actividad.

Effect of nerve growth factor on elderly degenerative knee osteoarthritis pain / 中国骨伤

OBJECTIVE@#To explore effect of nerve growth factor (NGF) antibody on knee osteoarthritis (KOA) pain model was evaluated by in vitro model.@*METHODS@#Thirty male SPF rats aged 28-week-old were divided into blank group (10 rats with anesthesia only). The other 20 rats were with monoiodoacetate (MIA) on the right knee joint to establish pain model of OA, and were randomly divided into control group (injected intraperitoneal injection of normal saline) and treatment group (injected anti-NGF) intraperitoneal after successful modeling, and 10 rats in each group. All rats were received retrograde injection of fluorogold (FG) into the right knee joint. Gait was assessed using catwalk gait analysis system before treatment, 1 and 2 weeks after treatment. Three weeks after treatment, right dorsal root ganglia (DRG) were excised on L4-L6 level, immunostained for calcitonin gene-related peptide (CGRP), and the number of DRGS was counted.@*RESULTS@#In terms of gait analysis using cat track system, duty cycle, swing speed and print area ratio in control and treatment group were significantly reduced compared with blank group (P<0.05). Compared with control group, duty cycle and swing speed of treatment group were significantly improved (P<0.05), and there was no significant difference in print area ratio between treatment group and blank group (P>0.05). The number of FG-labeled DRG neurons in control group was significantly higher than that in treatment group and blank group (P<0.05). The expression of CGRP in control group was up-regulated, and differences were statistically significant compared with treatment group (P<0.05).@*CONCLUSION@#Intraperitoneal injection of anti-NGF antibody inhibited gait injury and upregulation of CGRP in DRG neurons. The results suggest that anti-nerve growth factor therapy may be of value in treating knee pain. NGF may be an important target for the treatment of knee OA pain.

Effects of VX765 on osteoarthritis and chondrocyte inflammation in rats / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effects and underlying mechanisms of VX765 on osteoarthritis (OA) and chondrocytes inflammation in rats.@*METHODS@#Chondrocytes were isolated from the knee joints of 4-week-old Sprague Dawley (SD) rats. The third-generation cells were subjected to cell counting kit 8 (CCK-8) analysis to assess the impact of various concentrations (0, 1, 5, 10, 20, 50, 100 μmol/L) of VX765 on rat chondrocyte activity. An in vitro lipopolysaccharide (LPS) induced cell inflammation model was employed, dividing cells into control group, LPS group, VX765 concentration 1 group and VX765 concentration 2 group without obvious cytotoxicity. Western blot, real-time fluorescence quantitative PCR, and ELISA were conducted to measure the expression levels of inflammatory factors-transforming growth factor β 1 (TGF-β 1), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α). Additionally, Western blot and immunofluorescence staining were employed to assess the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1). Thirty-two SD rats were randomly assigned to sham surgery group (group A), OA group (group B), OA+VX765 (50 mg/kg) group (group C), and OA+VX765 (100 mg/kg) group (group D), with 8 rats in each group. Group A underwent a sham operation with a medial incision, while groups B to D underwent additional transverse incisions to the medial collateral ligament and anterior cruciate ligament, with removal of the medial meniscus. One week post-surgery, groups C and D were orally administered 50 mg/kg and 100 mg/kg VX765, respectively, while groups A and B received an equivalent volume of saline. Histopathological examination using HE and safranin-fast green staining was performed, and Mankin scoring was utilized for evaluation. Immunohistochemical staining technique was employed to analyze the expressions of matrix metalloproteinase 13 (MMP-13) and collagen type Ⅱ.@*RESULTS@#The CCK-8 assay indicated a significant decrease in cell viability at VX765 concentrations exceeding 10 μmol/L ( P<0.05), so 4 μmol/L and 8 μmol/L VX765 without obvious cytotoxicity were selected for subsequent experiments. Following LPS induction, the expressions of TGF-β 1, IL-6, and TNF-α in cells significantly increased when compared with the control group ( P<0.05). However, intervention with 4 μmol/L and 8 μmol/L VX765 led to a significant decrease in expression compared to the LPS group ( P<0.05). Western blot and immunofluorescence staining demonstrated a significant upregulation of Nrf2 pathway-related molecules Nrf2 and HO-1 protein expressions by VX765 ( P<0.05), indicating Nrf2 pathway activation. Histopathological examination of rat knee joint tissues and immunohistochemical staining revealed that, compared to group B, treatment with VX765 in groups C and D improved joint structural damage in rat OA, alleviated inflammatory reactions, downregulated MMP-13 expression, and increased collagen type Ⅱ expression.@*CONCLUSION@#VX765 can improve rat OA and reduce chondrocyte inflammation, possibly through the activation of the Nrf2 pathway.

Effect of Tongluo Juanbi Granules on Inflammatory Injury and Apoptosis of Osteoarthritis Based on TLR4/MyD88/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Tongluo Juanbi granules on chondrocyte apoptosis and Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway of rabbits with knee osteoarthritis （KOA） and study the mechanism of Tongluo Juanbi granules in the prevention and treatment of KOA. MethodThirty New Zealand rabbits were randomly assigned to the following five groups （n=6）： sham group， model group， low-dose and high-dose groups of Tongluo Juanbi granules （4.1 and 8.2 g·kg-1·d-1）， and celecoxib group （10.9 mg·kg-1·d-1）. The KOA model was established by destabilization of the medial meniscus （DMM） for six weeks. Six weeks after the modeling， the drug was given once a day for eight weeks. The pathological changes of cartilago articularis were observed by hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was performed to detect chondrocyte apoptosis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in synovial fluid. The mRNA and protein expression levels of genes related to the TLR4/MyD88/NF-κB signaling pathway were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the sham group， the cartilago articularis of the model group significantly degenerated. Mankin's score was increased （P<0.01）， and the contents of IL-1β and TNF-α in synovial fluid were increased （P<0.01）. The number of apoptosis of chondrocytes was increased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were up-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were down-regulated （P<0.01）. Compared with the model group， chondrocyte degeneration in both low-dose and high-dose groups of Tongluo Juanbi granules was improved， and Mankin's score was decreased （P<0.01）. The contents of IL-1β and TNF-α were decreased （P<0.01）， and the number of apoptosis of chondrocytes was decreased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were down-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were up-regulated （P<0.01）. In addition， in the above observation indicators， the high-dose group of Tongluo Juanbi granules was significantly superior to the low-dose group of Tongluo Juanbi granules. ConclusionTongluo Juanbi granules could inhibit chondrocyte apoptosis in rabbits with KOA and improve cartilage degeneration， which may be related to inhibiting inflammatory responses mediated by TLR4/MyD88/NF-κB signaling pathway.

Impact of a Tailored Self-Management Education Programme for Older Adults with Knee Osteoarthritis in a Multi-Ethnic Country / Jurnal Sains Kesihatan Malaysia

@#Self-management education program (SMEP) is essential in the knee osteoarthritis (OA) management. While the benefits of tailored SMEP have been highlighted in the literature, evidence on the effects of tailored knee OA SMEP for multiethnic populations, such as in Malaysia, remains limited. Therefore, the aim of this study was to conduct an intervention study on a tailored SMEP among Malaysian older adults who aged 60 years and above with knee OA. Participants aged 60 years and over with a diagnosis of knee OA were recruited. The intervention comprised four weekly structured group SMEP which was developed specifically for the multicultural population in Malaysia. Symptom’s severity and functional performance were assessed at baseline and six-week follow-up using the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS), 30 seconds sit to stand (30sST), time up and go (TUG), chair sit and reach (CSR), back stretch (BS), handgrip strength (HGS) and two-minute walk (2MW) tests. Of the 32 individuals recruited, 30 participants, mean age of 66.77 (±6.42) years, completed the post-intervention assessment. Improvements in mean KOOS domains scores were observed by between 1.3% - 8.6% from baseline to follow-up. Significant differences between baseline and followup scores were identified for 30sST (p < 0.05), TUG ( p < 0.001) and 2MW (p < 0.001) tests. A 4-week tailored SMEP delivered face to face by a physiotherapist, improved lower limb muscle strength, mobility, balance and endurance. Larger randomized controlled trials regarding the long-term effects of SMEP for older adults with OA is warranted.

Improvement effect and mechanism of “Layers adjusting external application”paste on synovial fibrosis in rats with knee osteoarthritis / 中国药房

OBJECTIVE To investigate the improvement effect and potential mechanism of “Layers adjusting external application” paste on synovial fibrosis （SF） in rats with knee osteoarthritis （KOA）. METHODS Male SD rats were randomly divided into sham operation group， KOA group and Layers adjusting external application group， with 8 rats in each group. KOA model was induced by the anterior cruciate ligament disruption method in KOA group and Layers adjusting external application group. Fourteen days after modeling， the Layers adjusting external application group was given “Layers adjusting external application” paste [Sanse powder （8 g for every 100 cm2）， Compound sanhuang ointment （5 g for every 100 cm2）] on the knee joint， 8 h every day， for 28 d in total. After the last administration， the degree of synovitis and fibrosis in rats was observed， and Krenn scoring was performed in each group. The expressions of collagen Ⅰ， high mobility group protein B1 （HMGB1） and phosphorylated nuclear factor-κB p65 （p-NF-κB p65） were detected in the synovial membrane； the contents of interleukin-1β （IL- 1β）， IL-6 and tumor necrosis factor-α （TNF-α） in serum as well as the expressions of fibrosis-related and HMGB1/Toll-like receptor 4 （TLR4）/NF-κB signaling pathway-related proteins and mRNA were detected in synovial tissue. RESULTS Compared with the sham operation group， the synovial lining cells in the KOA group showed significant proliferation and disordered arrangement， the inflammatory cell infiltration and collagen fiber deposition were obvious； the positive expressing cells of collagen Ⅰ， HMGB1 and p-NF-κB p65 were increased significantly； the contents of IL-1β， IL-6 and TNF-α in serum， the expressions of fibrosis-related protein （transforming growth factor-β， collagen Ⅰ， tissue inhibitor of metalloproteinase 1， α-smooth muscle actin） and their mRNA as well as theexpressions of HMGB1， TLR4 protein and their mRNA， the expressions of p-NF-κB p65 protein and NF-κB p65 mRNA were all increased significantly in synovial tissues of rats （P＜0.01）. Compared with the KOA group， the pathological changes in the synovial tissue of rats in Layers adjusting external application group were significantly improved， and the above quantitative indicators were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS “Layers adjusting external application” paste could significantly improve SF in KOA rats， the mechanism of which may be associated with the inhibition of the activation of HMGB1/ TLR4/NF-κB signaling pathway.

Mechanism of Traditional Chinese Medicine Intervening in Pyroptosis to Prevent and Treat Bone and Joint Related Diseases： A Review / 中国实验方剂学杂志

Osteoarthritis （OA）， rheumatoid arthritis （RA）， gouty arthritis （GA）， and intervertebral disc degeneration （IVDD） are the most common bone and joint-related diseases in clinical practice. They can all affect related joints， leading to joint pain， swelling， dysfunction， and other symptoms. The difference is that OA is mainly caused by joint wear and age-related degradation and is manifested as joint pain， stiffness， and limited movement. RA is an autoimmune disease， manifested as joint pain， swelling， morning stiffness， and systemic symptoms. GA is caused by abnormal uric acid metabolism， manifested as acute arthritis， and IVDD is caused by intervertebral disc degeneration. Studies have shown that the mechanism of the occurrence and development of these bone and joint diseases is extremely complex. Pyroptosis is closely related to these bone and joint-related diseases by participating in bone and joint inflammation， cartilage metabolism imbalance， extracellular matrix degradation， and pathological damage of bone and joint. Inhibition of bone and joint-related pyroptosis will effectively prevent and treat bone and joint-related diseases. At the same time， many studies have confirmed that traditional Chinese medicine （TCM） has a prominent curative effect and obvious advantages in the prevention and treatment of bone and joint-related diseases. TCM can reduce the inflammatory reaction of bone and joints， improve the pathological damage of bone and joint diseases， and relieve bone and joint pain by inhibiting pyroptosis. Therefore， this article aims to briefly explain the relationship between pyroptosis and the occurrence and development of bone and joint-related diseases and summarize the latest research reports on the intervention of pyroptosis in the treatment of bone and joint-related diseases by TCM monomers， TCM extracts， and TCM compounds. It offers new ideas for the in-depth study of the pathogenesis and drug treatment of bone and joint diseases and provides a basis for the clinical use of TCM to prevent and treat bone and joint diseases.

Traditional Chinese Medicine Regulates Autophagy to Prevent and Treat Osteoarthritis： A Review / 中国实验方剂学杂志

Osteoarthritis （OA） is a common chronic， highly prevalent， painful， and disabling degenerative joint disease. It has imposed a heavy burden on social healthcare and patients' psychology and economy due to its clinical symptoms such as impaired joint mobility and severe joint pain and the immature therapies. Studies have shown that OA is closely associated with articular cartilage dysfunction， synthesis and degradation disorders of chondrocyte extracellular matrix （ECM）， and joint inflammation. Moderate autophagy can restore the function of damaged chondrocytes， regulate chondrocyte apoptosis， and promote the synthesis and metabolism of ECM to alleviate the inflammation of joints and delay the onset and progression of OA. According to the clinical symptoms， OA can be classified into the category of impediment in traditional Chinese medicine. With the theories of holistic conception， treatment based on syndrome differentiation， and individualised diagnosis and treatment， traditional Chinese medicine has demonstrated definite effects in the treatment of OA in thousands of years of practice. Moreover， traditional Chinese medicine causes mild adverse reactions， and the patients have high tolerance and acceptance. This paper briefly explains the roles of autophagy and the related regulatory proteins， such as Unc-51-like autophagy-activated kinase 1 （ULK1）， Beclin-1， and microtubule-associated protein light chain 3 （LC3）， and details the latest research achievements in the prevention and control of OA by traditional Chinese medicines and its related markers via the regulation of autophagy， so as to provide a idea for the in-depth research in this field and the clinical application of traditional Chinese medicine in preventing and treating OA.

Fatores dietéticos e microbianos que interferem no tratamento da osteoartrite / Dietary and microbial factors that interfere in the treatment of osteoarthritis / Factoresdietéticos y microbianos que interfieren en el tratamento de la artroses

Introdução:A osteoartrite é uma doença degenerativa caracterizada pela deterioração progressiva da cartilagem articular, resultando em dor e incapacidade articular total em estágios avançados.Éconsiderada um dos distúrbios articulares mais comuns em todo o mundo e sua prevalência está aumentando constantemente devido ao envelhecimento, dietas inflamatórias e inatividade física. Objetivo:Investigar a contribuição da microbiota intestinal e dos componentes dietéticos, naperspectiva dediminuir as patologias associadas à osteoartrite. Metodologia:Trata-se de uma revisão integrativa desenvolvida a partir da seleção de artigos disponíveis escritos nalíngua inglesa, publicados nas bases de dados Pubmed e Science Direct. Resultados:No total, 25.583 artigos foram encontrados na busca, após os critérios de exclusão, 19 artigos compuseram o corpo de análise da revisão. Pesquisas em animais mostram que os efeitos induzidos por dieta rica em gordura foram evidentes e indicaram uma inflamação sistêmica de baixo grau resultando no agravamento da oesteoartritepor meio do aumento da degeneração da cartilagem. Dado ao impacto potencial da dieta na oesteoartrite, foram realizados estudos para avaliar a dieta mediterrânea, os níveis de ômega 3 e 6, vitamina C e E, com destaque para a oligofrutose, uma abordagem nova para tratar a oesteoartriteda obesidade. Conclusões:Conclui-se que apesar de já existir alguma evidência da utilidade da nutrição por meioda dieta alimentar como complemento da terapêutica na osteoartrite são necessários mais estudos que comprovem as intervenções na redução máxima dos marcadores inflamatórios ocasionando o alíviodos sintomas em pacientes com oesteoartrite (AU).

Introduction:Osteoarthritis is a degenerative disease characterized by progressive deterioration of the articular cartilage, resulting in pain and total joint disability in advanced stages. It is considered one of the most common joint disorders worldwide and its prevalence is steadily increasing due to aging, inflammatory diets and physical inactivity. Objective:The aim of this literature review was to investigate the contribution of intestinal microbiota and dietary components to try to reduce the pathologies associated with osteoarthritis.Methodology:This is an integrative review, developed from the selectionof available articles written in English, published in the Pubmed and Science Direct databases. Results:Intotal, 25.583articleswerefoundinthesearch,aftertheexclusioncriteria,19 articles madeupthebodyofanalysisofthereview.Animal research shows that the effects induced by a high-fat diet were evident and indicated low-grade systemic inflammation resulting in worsening osteoarthritis by increasing cartilage degeneration. Given the potential impact of diet on osteoarthritis, studies have been conducted to evaluate the Mediterranean diet, omega 3 and 6 levels, vitamin C and E, especially oligofructose, a new approach to treat obesity osteoarthritis.Conclusions:It is concluded that although there is already some evidence of the usefulness of nutrition through the diet as a complement to therapy in osteoarthritis, further studiesare needed to prove the interventions in the maximum reduction of inflammatory markers will cause the relief of symptoms in patients with osteoarthritis (AU).

Introducción: La artrosis es una enfermedad degenerativa caracterizada por el deterioro progresivo del cartílago articular, que se traduce en dolor e incapacidad articular total en estadios avanzados. Se considera uno de los trastornos articulares más comunes en todo el mundo y su prevalencia aumenta constantemente debido al envejecimiento, las dietas inflamatorias y la inactividad física. Objetivo: El objetivo de esta revisión fue investigar la contribución de la microbiota intestinal y los componentes de la dieta, en un intento por reducirlas patologías asociadas a la artrosis. Metodología: Se trata de una revisión integradora, desarrollada a partir de la selección de artículos disponibles escritos en inglés, publicados en las bases de datos Pubmed y Science Direct. Resultados: En total, se encontraron 25.583 artículos en la búsqueda, después de los criterios de exclusión, 19 artículos conformaron el cuerpo de análisis de la revisión.La investigación en animales muestra que los efectos inducidos por una dieta alta en grasas fueron evidentes e indicaron una inflamación sistémica de bajo grado que resultó en un empeoramiento de la osteoartritis a través de una mayor degeneración del cartílago. Dado el impacto potencial de la dieta en la osteoartritis, se han realizado estudios para evaluar ladieta mediterránea, los niveles de omega 3 y 6, vitamina C y E, con énfasis en la oligofructosa, un nuevo enfoque para tratar la osteoartritis por obesidade.Conclusiones: Se concluye que aunque ya existe alguna evidencia de la utilidad de la nutrición a través de la dieta como complemento al tratamiento de la artrosis, son necesarios más estudios que prueben intervenciones en la reducción máxima de los marcadores inflamatorios, provocando el alivio de los síntomas en pacientes con osteoartritis (AU).

Does total knee arthroplasty affect pelvic movements? A prospective comparative study

SUMMARY OBJECTIVE: Pathology in any segment of the spine-pelvis-lower extremity may impair the global postural balance, leading to compensatory alterations in other parts. The aim of this study was to compare the pelvic movements of patients suffering from knee osteoarthritis with patients who underwent total knee arthroplasty and healthy controls. METHODS: This study was performed at the Department of Orthopedics and Traumatology Clinic of a Cankiri State Hospital between April 2021 and February 2022. This study included 84 participants. Of them, 31 patients who underwent total knee arthroplasty between 2018 and 2020 years were selected as the total knee arthroplasty group, while 28 patients with knee osteoarthritis were selected as the knee osteoarthritis group. In the control group, there were 25 healthy individuals. Exclusion criteria from the study included any kind of neurological disease, an inability to walk a distance of 100 m unassisted, or a history of surgery to the lower limb. Pelvic movements (i.e., tilt, rotation, and obliquity) and gait parameters (i.e., "gait velocity," "cadence," and "stride length") were assessed using a wireless tri-axial accelerometer. RESULTS: Total knee arthroplasty and control groups had decreased minimum anterior tilt of the pelvis, decreased maximum anterior tilt, and decreased oblique range of the pelvis compared with the knee osteoarthritis group. In comparison with the control group, gait velocity and length of stride during gait were remarkably lower in both knee osteoarthritis and total knee arthroplasty groups. CONCLUSION: In this study, total knee arthroplasty was found to affect pelvic movements. It was thought that total knee arthroplasty changed these variables, probably owing to the frontal and sagittal plane alignment correction through surgery.

Development of a convolutional neural network for diagnosing osteoarthritis, trained with knee radiographs from the ELSA-Brasil Musculoskeletal / Desenvolvimento de rede neural convolucional para o diagnóstico radiográfico de osteoartrite dos joelhos no ELSA-Brasil Musculoesquelético

Abstract Objective: To develop a convolutional neural network (CNN) model, trained with the Brazilian "Estudo Longitudinal de Saúde do Adulto Musculoesquelético" (ELSA-Brasil MSK, Longitudinal Study of Adult Health, Musculoskeletal) baseline radiographic examinations, for the automated classification of knee osteoarthritis. Materials and Methods: This was a cross-sectional study carried out with 5,660 baseline posteroanterior knee radiographs from the ELSA-Brasil MSK database (5,660 baseline posteroanterior knee radiographs). The examinations were interpreted by a radiologist with specific training, and the calibration was as established previously. Results: The CNN presented an area under the receiver operating characteristic curve of 0.866 (95% CI: 0.842-0.882). The model can be optimized to achieve, not simultaneously, maximum values of 0.907 for accuracy, 0.938 for sensitivity, and 0.994 for specificity. Conclusion: The proposed CNN can be used as a screening tool, reducing the total number of examinations evaluated by the radiologists of the study, and as a double-reading tool, contributing to the reduction of possible interpretation errors.

Resumo Objetivo: Desenvolver um modelo computacional - rede neural convolucional (RNC) - treinado com radiografias da linha de base do Estudo Longitudinal de Saúde do Adulto Musculoesquelético (ELSA-Brasil Musculoesquelético), para a classificação automática de osteoartrite dos joelhos. Materiais e Métodos: Trata-se de um estudo transversal abrangendo todos os exames da linha de base do ELSA-Brasil Musculoesquelético (5.660 radiografias dos joelhos em incidência posteroanterior). Os exames foram interpretados por médico radiologista com treinamento específico e calibração previamente publicada. Resultados: A RNC desenvolvida apresentou área sob a curva característica de operação do receptor de 0,866 (IC 95%: 0,842-0,882). O modelo pode ser calibrado para alcançar, não simultaneamente, valores máximos de 0,907 para acurácia, 0,938 para sensibilidade e 0,994 para especificidade. Conclusão: A RNC desenvolvida pode ser utilizada como ferramenta de triagem, reduzindo o número total de exames avaliados pelos radiologistas do estudo, e/ou como ferramenta de segunda leitura, contribuindo com a redução de possíveis erros de interpretação.

Acupuncture in the Treatment of a Series of Patients with Chronic Pain Associated with Hip Osteoarthritis / Acupuntura no tratamento de uma série de pacientes com dor crônica associado à osteoartrite de quadril

Abstract Objective Hip osteoarthritis (HO) causes pain and deranges functioning. Surgical treatment is the preferred approach in severe cases, but clinical comorbidities, age and the long waiting list may compromise quality of life. This study aimed to describe the results of acupuncture for the control pain and improvement of functioning in subjects with HO. Method Twelve severe HO patients were treated with ten weekly sessions of a standardized acupuncture point protocol. Pain intensity was assessed with the Visual Analog Pain Scale (VAS) and quality of life with WOMAC Index. Results Pain intensity (VAS) reduced from 75.8 ± 18.8 mm to 20.0 ± 22.6 mm after 10 acupuncture sessions and 48.3 ± 26.6mm in the follow-up (ANOVA F = 7.99; p < 0.001). WOMAC Index values reduced from 74.7 ± 12.7 to 45.7 ± 22.1 and 54.6 ± 22.9 at the same timepoints. Conclusion Acupuncture is an effective conservative rehabilitation strategy to reduce pain and improve quality of life in subjects with severe HO.

Resumo Objetivo A osteoartrite (OA) de quadril causa dor e perda da funcionalidade. O tratamento cirúrgico é a procedimento de escolha nos casos graves, mas as comorbidades clínicas, a idade e a longa lista de espera podem comprometer a qualidade de vida. Este estudo teve como objetivo descrever os resultados da acupuntura no controle da dor e melhora da funcionalidade em indivíduos com OA de quadril. Método Doze pacientes com OA de quadril grave foram tratados com dez sessões semanais de um protocolo padronizado de pontos de acupuntura. A intensidade da dor foi avaliada pela Escala Visual Analógica de Dor (EVA) e a qualidade de vida pelo Índice WOMAC. Resultados A intensidade da dor (EVA) reduziu de 75,8 ± 18,8mm para 20,0 ± 22,6mm após 10 sessões de acupuntura e 48,3 ± 26,6mm no período de seguimento (ANOVA F = 7,99; p < 0,001). Os valores do Índice WOMAC reduziram de 74,7 ± 12,7 para 45,7 ± 22,1 e 54,6 ± 22,9 nos mesmos momentos. Conclusão A acupuntura é uma estratégia de reabilitação conservadora eficaz para reduzir a dor e melhorar a qualidade de vida em indivíduos com OA de quadril grave.