TNF-α promotes osteocyte necroptosis by upregulating TLR4 in postmenopausal osteoporosis.

Postmenopausal osteoporosis (PMOP) is a common kind of osteoporosis that is associated with excessive osteocyte death and bone loss. Previous studies have shown that TNF-α-induced osteocyte necroptosis might exert a stronger effect on PMOP than apoptosis, and TLR4 can also induce cell necroptosis, as confirmed by recent studies. However, little is known about the relationship between TNF-α-induced osteocyte necroptosis and TLR4. In the present study, we showed that TNF-α increased the expression of TLR4, which promoted osteocyte necroptosis in PMOP. In patients with PMOP, TLR4 was highly expressed at skeletal sites where exists osteocyte necroptosis, and high TLR4 expression is correlated with enhanced TNF-α expression. Osteocytes exhibited robust TLR4 expression upon exposure to necroptotic osteocytes in vivo and in vitro. Western blotting and immunofluorescence analyses demonstrated that TNF-α upregulated TLR4 expression in vitro, which might further promote osteocyte necroptosis. Furthermore, inhibition of TLR4 by TAK-242 in vitro effectively blocked osteocyte necroptosis induced by TNF-α. Collectively, these results suggest a novel TLR4-mediated process of osteocyte necroptosis, which might increase osteocyte death and bone loss in the process of PMOP.

Self-management on heart failure: A meta-analysis.

BACKGROUND AND AIMS: Heart failure (HF) is a severe public health problem all over the World. Self-management is an effective method to progress self-care ability. However, the role of self-management in heart failure has not been thoroughly elucidated. METHODS: The research articles related to heart failure were searched by the PubMed, Embase, Cochrane databases, and China National Knowledge Database on articles published through March 2020. The average 95% of confidence intervals (CIs) were used to calculate using random-effects or fixed-effects. Review Manager (version 5.2) was adopted for meta-analysis, sensitivity analysis, and bias analysis. RESULTS: Eight (8) eligible studies with 1707 patients with HF were included in this analysis. In the Meta-analysis showed significant differences for Self-management (SM) groups in Dutch Heart Failure Knowledge Scale (DHFK) (MD = 1.36, 95%CI [-0.03, 2.75], P = 0.04; I2 = 83%), in Self-Care of Heart Failure Index (SCHFI) (MD = 5.51, 95%CI [0.62, 10.40], P = 0.03; I2 = 70%), and in Self-Efficacy for Managing Chronic Disease Scale (SEMCDI) (I2 = 47%, Z = 5.43, P of over effect < 0.0001) than control groups. One bias is detected as attrition bias, and another one is reporting bias. Sensitivity analysis satisfied the stability of the results. CONCLUSION: Self-management was associated with significant outcomes in patients with HF through knowledge, attitude, and practice (KAP).