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To investigate whether TP53-induced glycolysis and apoptosis regulator (TIGAR) participates in compression-induced intervertebral disc (IVD) degeneration, and to determine the regulatory effect of TIGAR on nucleus pulposus (NP) cell autophagy and apoptosis following compression-induced injuries. IVD tissues were collected from human patients undergoing surgery (n = 20) and skeletally mature Sprague-Dawley rats (n = 15). Initially, the effect of compression on the expression of TIGAR was evaluated with in vivo and in vitro models. In addition, TIGAR was silenced to investigate the regulatory effect of TIGAR on compression-induced intracellular reactive oxygen species (ROS) levels, autophagy, and apoptosis in rat NP cells. Furthermore, the P53 inhibitor pifithrin-α (PFTα) and SP1 inhibitor mithramycin A were employed to detect expression level changes of TIGAR and autophagy-associated target molecules. TIGAR expression of NP cells increased gradually in human degenerative IVDs and in rat NP cells under compression both in vivo and in vitro. TIGAR knockdown enhanced compression-induced intracellular ROS generation and the NADPH/NADP+ and GSH/GSSG ratios. Moreover, TIGAR knockdown amplified the compression-induced caspase-3 activation and the apoptosis rate of rat NP cells. Likewise, knockdown of TIGAR significantly accelerated LC3B expression and autophagosome formation in rat NP cells during compression-induced injuries. The results also established that mithramycin A could inhibit TIGAR expression and autophagy levels in NP cells under compression conditions, while PFTα had no similar effect. Our data demonstrated that TIGAR acted as an important endogenous negative regulator of ROS levels, which might inhibit compression-induced apoptosis and autophagy through SP1-dependent mechanisms.

Background: MiR-92a has been discovered to be involved in the malignant behavior of various types of cancers. However, the particular clinical and prognostic roles of miR-92a in tumors still need to be identified more precisely. The current meta-analysis assessed the prognostic value of miR-92a in various carcinomas. Methods: Systematic literature searches of PubMed, PMC, Web of Science (WOS), Embase in English and Wanfang, SinoMed and the China National Knowledge Infrastructure (CNKI) in Chinese up to Jan 15th 2019 were conducted for eligible studies. Twenty studies involving a total of 2573 patients were included in the analysis. Pooled hazard ratios (HR) for overall survival (OS) and disease-free survival (DFS), progression-free survival (PFS) and recurrence-free survival (RFS) were assessed using fixed-effects and random-effects models. Meta-regression and subgroup analyses were carried out to explore the source of heterogeneity. Odds ratio (OR) and 95%CIs were applied to evaluate the relationship between miR-92a expression levels and clinicopathological characteristics. Results: A significant association between miR-92a levels and OS (HR=2.18) was identified. The random pooling model also revealed significance of consistency (HR=2.14), indicating that the stability of the results. Subgroup analyses were performed and the corresponding significance was recognized in Chinese cancer patients (HR=2.35), studies of specimen derived from tissues (HR=2.43), non-hematological cancer (HR=2.35), osteosarcoma (HR=2.54), non-small cell lung cancer (HR=2.33), hepatocellular carcinoma (HR=2.40) and so on. There were significant relations observed of the expression level of miR-92a to tumor size (≥5 vs

The association between TNF-α-308(G/A) and -238(G/A) polymorphisms and the susceptibility of non-traumatic osteonecrosis of the femoral head (NONFH) was investigated in many studies with conflicting results. We aimed to conduct a meta-analysis to evaluate the relationship between them comprehensively. Relevant literatures published in PubMed, Web of Science, Embase, Cochrane library databases, China National Knowledge Infrastructure (CNKI), WANFANG Data, and China Science and Technology Journal Database (CSTJ) updated to January 30, 2018, were reviewed by two investigators independently. Odds ratios (ORs) and its 95% confidence intervals (95% CIs) were calculated by a fixed-effect model based on the indistinctive heterogeneity. For TNF-α-308(G/A) polymorphism, we recruited five studies including 432 NONFH patients and 760 controls and a statistically significant association was identified in Asians in four modes consisting of alleles mode (OR = 0.648, 95% CI 0.475–0.885), homozygote mode (OR = 0.330, 95% CI 0.136–0.802), dominant mode (OR = 0.344, 95% CI 0.143–0.827), and recessive mode (OR = 0.674, 95% CI 0.468–0.971), but no significant association was observed in Caucasians. For TNF-α-238(G/A) polymorphism, three eligible studies including 275 cases and 610 controls were evaluated and there was a significant association in alleles mode (OR = 0.270, 95% CI 0.4148–0.490) as well as recessive mode (OR = 0.254, 95% CI 0.138–0.468). This meta-analysis shows that TNF-α-308(G/A) and -238(G/A) polymorphisms are associated with the susceptibility of NONFH, while the significant association for 308(G/A) is mainly observed in Asians.