Necroptotic TNFα-Syndecan 4-TNFα Vicious Cycle as a Therapeutic Target for Preventing Temporomandibular Joint Osteoarthritis

Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Meta-Analysis of Saturated Fatty Acid Intake and Breast Cancer Risk

The associations between saturated fatty acid (SFA) consumption and risk of breast cancer (BC) remains inconclusive. Therefore, we conducted this meta-analysis to determine the quantitative relations between dietary SFA intake and incidence of BC.Literatures published up to April 2015 were systematically screened through Pubmed and Web of Science. Relevant publication quality was evaluated by conducting the Newcastle-Ottawa scale. We used fixed effects models or random effect models to calculate the summary relative risks (RRs) and odds ratios (ORs), and conducted sensitivity analyses and evaluated the publication bias.We identified a total of 52 studies (24 cohort studies and 28 case–control studies), with over 50,000 females diagnosed with BC. The associations between dietary SFA intake and risk of BC were 1.18 for case–control studies (high vs low intake, 95% confidence interval [CI] = 1.03–1.34) and 1.04 for cohort studies (95% CI = 0.97–1.11). When restricted analyses to population-based studies, positive associations were observed for both cohort (RR [95% CI] = 1.11 [1.01–1.21]) and case–control studies (OR [95% CI] = 1.26 [1.03–1.53]). Additionally, for case–control studies, significant positive associations between higher SFA intake and BC risk were observed for Asian (OR [95% CI] = 1.17 [1.02–1.34]) and Caucasian (OR [95% CI] = 1.19 [1.00–1.41]), as well as for postmenopausal women (OR = 1.33, 95% CI: 1.02–1.73). In contrast, higher dietary SFA intake was not associated with risk of BC among premenopausal women, in cohort studies or hospital-based studies.A positive association between higher dietary SFA intake and postmenopausal BC risk was observed in case–control but not in cohort studies. More studies are warranted to confirm these findings.     

新冠肺炎疫情下艾灸防治帕金森病的临床应用分析＊

帕金森病（Parkinson''s disease，PD）是仅次于阿尔茨海默病的世界第二大神经系统退行性疾病，随着老龄化社会的到来，PD患病率呈明显上升趋势。全球爆发的新型冠状病毒肺炎（简称新冠肺炎）是一种急性传染性疾病，严重威胁人们的身体健康和生命安全。PD患者大多为老年人且合并有基础疾病，体质普遍较弱，是新冠肺炎的易感人群，一旦染病则发展为重症的风险很高。中医艾灸疗法在治疗PD及防治疫病方面发挥了很好的辅助治疗效果。通督扶阳灸法联合强壮穴艾灸治疗，既可以帮助PD患者改善临床症状，延缓病情进展，又可以提高机体免疫功能，增强抗病能力而防治新冠肺炎。