Myopenia and Musculoskeletal Aging in Rheumatoid Arthritis

Rheumatoid arthritis (RA), the commonest inflammatory arthritis, is a debilitating disease leading to decreased functional capacity, social disability and reduced quality of life. RA affects multisystems with chronic inflammatory disease characterized by destructive synovitis and muscular dysfunction leading to premature musculoskeletal aging, which has been coined with many terms including myopenia, sarcopenia, cachexia, muscle failure and muscle wasting. Myopenia is described as the presence of clinically relevant muscle wasting due to any illness at any age, associated with impaired muscle function, increased morbidity and mortality. RA myopenia has significantly less muscle mass compared to the general population muscle loss showing preservation or slight increase in fat mass. RA myopenia is unique compared to chronic disease-related myopenia in cancer, chronic heart failure, kidney disease and chronic infection as it is rarely accompanied by a net weight loss. RA myopenia has younger-age onset compared to elderly primary sarcopenia, while higher-grade inflammation has been considered as the pathophysiology of muscle wasting. Research, however, indicates that inflammation itself cannot fully explain the high prevalence of muscle wasting in RA. This chapter aims to review the literature on the casual relationships among RA myopenia, premature musculoskeletal aging and management strategies to delay musculoskeletal aging

Humoral immune response to proteins of human cytomegalovirus latency-associated transcripts

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Pathological mechanisms and therapeutic outlooks for arthrofibrosis

Arthrofibrosis is a fibrotic joint disorder that begins with an inflammatory reaction to insults such as injury, surgery and infection. Excessive extracellular matrix and adhesions contract pouches, bursae and tendons, cause pain and prevent a normal range of joint motion, with devastating consequences for patient quality of life. Arthrofibrosis affects people of all ages, with published rates varying. The risk factors and best management strategies are largely unknown due to a poor understanding of the pathology and lack of diagnostic biomarkers. However, current research into the pathogenesis of fibrosis in organs now informs the understanding of arthrofibrosis. The process begins when stress signals stimulate immune cells. The resulting cascade of cytokines and mediators drives fibroblasts to differentiate into myofibroblasts, which secrete fibrillar collagens and transforming growth factor-β (TGF-β). Positive feedback networks then dysregulate processes that normally terminate healing processes. We propose two subtypes of arthrofibrosis occur: active arthrofibrosis and residual arthrofibrosis. In the latter the fibrogenic processes have resolved but the joint remains stiff. The best therapeutic approach for each subtype may differ significantly. Treatment typically involves surgery, however, a pharmacological approach to correct dysregulated cell signalling could be more effective. Recent research shows that myofibroblasts are capable of reversing differentiation, and understanding the mechanisms of pathogenesis and resolution will be essential for the development of cell-based treatments. Therapies with significant promise are currently available, with more in development, including those that inhibit TGF-β signalling and epigenetic modifications. This review focuses on pathogenesis of sterile arthrofibrosis and therapeutic treatments. © 2019, The Author(s)

Massage Alleviates Delayed Onset Muscle Soreness after Strenuous Exercise: A Systematic Review and Meta-Analysis

Purpose: The purpose of this systematic review and meta-analysis was to evaluate the effects of massage on alleviating delayed onset of muscle soreness (DOMS) and muscle performance after strenuous exercise.Method: Seven databases consisting of PubMed, Embase, EBSCO, Cochrane Library, Web of Science, CNKI and Wanfang were searched up to December 2016. Randomized controlled trials (RCTs) were eligible and the outcomes of muscle soreness, performance (including muscle maximal isometric force (MIF) and peak torque) and creatine kinase (CK) were used to assess the effectiveness of massage intervention on DOMS.Results: Eleven articles with a total of 23 data points (involving 504 participants) satisfied the inclusion criteria and were pooled in the meta-analysis. The findings demonstrated that muscle soreness rating decreased significantly when the participants received massage intervention compared with no intervention at 24 h (SMD: –0.61, 95% CI: –1.17 to –0.05, P = 0.03), 48 h (SMD: –1.51, 95% CI: –2.24 to –0.77, P < 0.001), 72 h (SMD: –1.46, 95% CI: –2.59 to –0.33, P = 0.01) and in total (SMD: –1.16, 95% CI: –1.60 to –0.72, P < 0.001) after intense exercise. Additionally, massage therapy improved MIF (SMD: 0.56, 95% CI: 0.21–0.90, P = 0.002) and peak torque (SMD: 0.38, 95% CI: 0.04–0.71, P = 0.03) as total effects. Furthermore, the serum CK level was reduced when participants received massage intervention (SMD: –0.64, 95% CI: –1.04 to –0.25, P = 0.001).Conclusion: The current evidence suggests that massage therapy after strenuous exercise could be effective for alleviating DOMS and improving muscle performance

Alternative splicing of leptin receptor overlapping transcript in osteosarcoma

Alternative splicing of RNA is an essential mechanism that increases proteomic diversity in eukaryotic cells. Aberrant alternative splicing is often associated with various human diseases, including cancer. We conducted whole-transcriptome analysis of 18 osteosarcoma bone samples (paired normal—tumor biopsies). Using RNA-seq, we identified statistically significant (FDR <0.05) 26 differentially expressed transcript variants of leptin receptor overlapping transcript (LEPROT) gene. Some of the transcripts were overexpressed in normal cells, whereas others were overexpressed in tumor cells. The function of LEPROT is not completely understood. Herein, we highlight a possible association between OS and aberrant alternative splicing events and its interaction with the expression of LEPROT. We also discuss the role of LEPROT in regulating growth hormone and its receptor, and the relationship with initiation and progression of OS. This research study may help to understand the association of alternative splicing mechanism in OS and in tumorigenesis more generally. Further, LEPROT gene can also be considered as a potential biomarker of osteosarcoma

Effects of follicle-stimulating hormone on fat metabolism and cognitive impairment in women during menopause

Lipid metabolism disorder is a common pathological manifestation of menopausal women, and is also an important risk factor for many diseases at this stage of life. Epidemiological studies have shown that high levels of follicle-stimulating hormone (FSH) in menopausal women are closely associated with changes in body composition, central obesity, and cognitive decline. Exogenous FSH causes growth and proliferation of adipose, whereas blockage of the FSH signaling pathway leads to decline in adipose. Mechanistically, FSH, FSH receptor (FSHR), G protein coupling, gene mutation and other pathways are involved in adipogenesis and cognitive impairment. Here, we review the critical role and potential interactions of FSH in adipogenesis and cognitive impairment in menopausal women. Further understanding of the exact mechanisms of FSH aggravating obesity and cognitive impairment may provide a new perspective for promoting healthy aging in menopausal women

Dragon blood resin ameliorates steroid-induced osteonecrosis of femoral head through osteoclastic pathways

Objective: Dragon’s Blood resin (DBR) is a traditional medicinal substance renowned for its diverse pharmacological effects, which consists of potent anti-inflammatory, antioxidant and angiogenic properties. This study aimed to elucidate its therapeutic mechanism in alleviating steroid-induced osteonecrosis of the femoral head (SIONFH).Methods: Techniques such as SPR and LC-MS were employed to identify and analyze the target proteins of DBR in bone marrow macrophages (BMMs). In vitro, BMMs were treated with RANKL and DBR, and TRAcP staining and actin belt staining were utilized to assess osteoclast activity. The inhibitory effects and underlying mechanisms of DBR on osteoclastogenesis and reactive oxygen species (ROS) generation were determined using real-time PCR, western blotting and immunofluorescence staining. An in vivo SIONFH rat model was set up to assess the curative impacts of DBR using micro-CT scanning and pathological staining.Results: Bioinformatic tools revealed a pivotal role of osteoclast differentiation in SIONFH. Proteomic analysis identified 164 proteins binding in BMMs. In vitro assessments demonstrated that DBR hindered osteoclastogenesis by modulating the expression of specific genes and proteins, along with antioxidant proteins including TRX1 and Glutathione Reductase. Notably, the resin effectively inhibited the expression of crucial proteins, such as the phosphorylation of JNK and the nuclear localization of p65 within the TRAF6/JNK and NFκB signaling pathways. In vivo experiments further confirmed that DBR mitigated the onset of SIONFH in rats by curbing osteoclast and ROS activities.Conclusion: These findings underscore the potential of Dragon’s Blood as an effective administration for early-stage SIONFH, shedding light on its therapeutic influence on ROS-mediated osteoclastic signaling pathways

Privileged Prior Information Distillation for Image Matting

Performance of trimap-free image matting methods is limited when trying to decouple the deterministic and undetermined regions, especially in the scenes where foregrounds are semantically ambiguous, chromaless, or high transmittance. In this paper, we propose a novel framework named Privileged Prior Information Distillation for Image Matting (PPID-IM) that can effectively transfer privileged prior environment-aware information to improve the performance of students in solving hard foregrounds. The prior information of trimap regulates only the teacher model during the training stage, while not being fed into the student network during actual inference. In order to achieve effective privileged cross-modality (i.e. trimap and RGB) information distillation, we introduce a Cross-Level Semantic Distillation (CLSD) module that reinforces the trimap-free students with more knowledgeable semantic representations and environment-aware information. We also propose an Attention-Guided Local Distillation module that efficiently transfers privileged local attributes from the trimap-based teacher to trimap-free students for the guidance of local-region optimization. Extensive experiments demonstrate the effectiveness and superiority of our PPID framework on the task of image matting. In addition, our trimap-free IndexNet-PPID surpasses the other competing state-of-the-art methods by a large margin, especially in scenarios with chromaless, weak texture, or irregular objects.Comment: 15 pages, 7 figure