Causal Relationship between Mitochondrial Biological Function and Periodontitis: Evidence from a Mendelian Randomization Study.

A growing number of studies indicate that mitochondrial dysfunction serves as a pathological mechanism for periodontitis. Therefore, this two-sample Mendelian randomization (MR) study was carried out to explore the causal associations between mitochondrial biological function and periodontitis, because the specific nature of this causal relationship remains inconclusive in existing MR studies. Inverse variance weighting, Mendelian randomization-Egger, weighted mode, simple mode, and weighted median analyses were performed to assess the causal relationships between the exposure factors and periodontitis. The results of the present study revealed a causal association between periodontitis and medium-chain specific acyl-CoA dehydrogenase (MCAD), malonyl-CoA decarboxylase (MLYCD), glutaredoxin 2 (Grx2), oligoribonuclease (ORN), and pyruvate carboxylase (PC). Notably, MCAD and MLYCD are causally linked to periodontitis, and serve as protective factors. However, Grx2, ORN, and PC function as risk factors for periodontitis. Our study established a causal relationship between mitochondrial biological function and periodontitis, and such insights may provide a promising approach for treating periodontitis via mitochondrial regulation.

A comparison of non-intubated video-assisted thoracic surgery with spontaneous ventilation and intubated video-assisted thoracic surgery: a meta-analysis based on 14 randomized controlled trials.

BACKGROUND: Video-assisted thoracic surgery (VATS) generally involves endotracheal intubation under general anesthesia. However, inevitably, this may cause intubation-related complications and prolong the postoperative recovery process. Gradually, non-intubated video-assisted thoracic surgery (NIVATS) is increasingly being utilized. However, its safety and efficacy remain controversial. METHODS: Randomized controlled trials (RCTs) published up to August 2020 were selected from the Cochrane Library, Web of Science, PubMed, Embase, and ClinicalTrials.gov databases and included in this study according to the inclusion criteria. Two reviewers screened these RCTs and independently extracted the relevant data. After assessing the risk of bias in these RCTs, a meta-analysis was performed using Review Manager 5.3. Pooled data were meta-analyzed using a random-effects model. RESULTS: Meta-analysis data demonstrated that the mean difference (MD) in the length of hospital stay between non-intubated patients and intubated patients was -1.41 days, with a 95% confidence interval (CI) of -2.47 to -0.34 (P=0.01). The visual analogue scale (VAS) score between the two groups showed a MD of -0.34 (95% CI: -0.58 to -0.10; P=0.006). Patients who underwent NIVATS presented with lower rates of overall complications [odds ratio (OR) 0.41; 95% CI: 0.25 to 0.67; P=0.0004], air leak (OR 0.45; 95% CI: 0.24 to 0.87; P=0.02), pharyngeal discomfort (OR 0.08; 95% CI: 0.04 to 0.17; P<0.00001), hoarseness (OR 0.06; 95% CI: 0.02 to 0.21; P<0.00001), and gastrointestinal reactions (OR 0.23; 95% CI: 0.10 to 0.53; P=0.0005) compared to intubated patients. The anesthesia satisfaction scores in the NIVATS group were significantly higher than those of the VATS group (MD 0.50; 95% CI: 0.12 to 0.88; P=0.009). However, there were no statistically significant differences in the length of operation time (MD 0.90 hours; 95% CI: -0.23 to 2.03; P=0.12) and surgical field satisfaction (1 point) (OR 0.73; 95% CI: 0.34 to 1.59; P=0.43) between the two groups. CONCLUSIONS: NIVATS is a safe and feasible form of intervention that can reduce the postoperative pain and complications of various systems and shorten hospital stay duration without prolonging the operation time.

Identification of TRAF6 as a ubiquitin ligase engaged in the ubiquitination of SopB, a virulence effector protein secreted by Salmonella typhimurium.

The phosphoinositide phosphatase SopB is one of the effectors injected by Salmonella typhimurium (S.typhimurium) that diversifies its function through a ubiquitin-dependent differential localization. However, it is unclear which E3 ubiquitin ligase is responsible for ubiquitination of SopB. Based on the E1-E2-E3 trio of enzymes responsible for the ubiquitin activation and translocation to substrate proteins, we constructed an in vitro assay of SopB ubiquitination. Using this assay, we purified an E3 ubiquitin ligase, TRAF6, from the Henle-407 S100 extraction that may be responsible for the ubiquitination of SopB. To investigate the functional correlation of TRAF6, we showed that recombinant TRAF6 specifically ubiquitinates SopB in a dose-dependent manner in vitro. Upon infection, the ubiquitination of SopB was absolutely blocked by TRAF6 deletion, as shown in Traf6(-/-) mouse embryonic fibroblasts (MEFs) compared with Traf6(+/+) MEFs. However, the ectopic expression of TRAF6 in Traf6(-/-) MEFs rescued the two species of ubiquitin-conjugated SopB, which strengthens the role of TRAF6 in SopB ubiquitination. The analysis of E2 revealed that UbcH5c and not other E2 conjugating enzymes are required for TRAF6-mediated SopB ubiquitination both in vitro and in vivo. In summary, these results suggest the relevance of UbcH5c/TRAF6 in SopB during S.typhimurium infection and thereby imply that S.typhimurium has evolved a mechanism of utilizing the host's E3 ubiquitin ligase to modify and modulate the function of its effector protein in order to ensure pathogen and host cell survival.