miR-25-3p ameliorates SAE by targeting the TLR4/NLRP3 axis.

Sepsis-associated encephalopathy (SAE) is a severe complication of sepsis. It has been reported that miR-25-3p is closely related to the development of sepsis. However, the detailed mechanism of miR-25-3p in SAE requires further investigation. Caecum ligation and puncture (CLP) was performed to induce SAE in vivo. LPS stimulation was applied to mimic the in vitro inflammatory model. The expression levels of TLR4 and NLRP3 in the cerebral cortex were evaluated by immunofluorescence. The gene and protein expression levels were determined by qRT-PCR and a western blot analysis. ELISA was used to detect the levels of inflammatory cytokines. The interaction between miR-25-3p and TLR4 was validated by a dual luciferase reporter assay. TLR4 and NLRP3 were highly expressed in the cerebral cortex of SAE mice, while miR-25-3p was expressed at low levels. Activation of the inflammasome, increased release of cytokines and microglial activation were also observed in the SAE mouse model. The overexpression of miR-25-3p inhibited the expression of LPS-induced cytokines and microglial activation. Furthermore, miR-25-3p inhibited TLR4 expression by directly targeting TLR4. The anti-inflammatory effect of miR-25-3p in LPS-induced CHME5 was reversed by TLR4 overexpression. miR-25-3p overexpression attenuated the activation of microglia in SAE by inhibiting the NLRP3/IL-1ß/IL-18 axis by directly targeting TLR4, suggesting that miR-25-3p may be a potential target for SAE diagnosis and treatment.

Cardio-Metabolic Risk Factors in Scottish South Asian and Caucasian Youth.

(1) Background: Scotland has one of the highest rates of obesity in the Western World, it is well established that poor weight profiles, and particularly abdominal obesity, is strongly associated with Type II diabetes and cardiovascular diseases. Whether these associations are apparent in ethnic population groups in Scotland is unclear. The purpose of this study was to examine the associations between different measures of fatness with clustered cardio metabolic risk factors between Scottish South Asian adolescents and Scottish Caucasian adolescents; (2) Methods: A sample of 208 Caucasian adolescents and 52 South Asian adolescents participated in this study. Stature, waist circumference, body mass index, blood pressure, physical activity, and cardiovascular disease (CVD) risk were measured; (3) Results: Significant, partial correlations in the South Asian cohort between body mass index (BMI) and individual risk factors were generally moderate. However, correlations between Waist circumference (WC) and individual risk factors were significant and strong. In the Caucasian cohort, a significant yet weak correlation between WC and total cholesterol (TG) was noted although no other associations were evident for either WC or BMI. Multiple regression analysis revealed that both BMI and WC were positively associated with CCR (p < 0.01) in the South Asian group and with the additional adjustment of either WC or BMI, the independent associations with clustered cardio-metabolic risk (CCR) remained significant (p < 0.005); (4) Conclusions: No positive relationships were found between BMI, WC, and CCR in the Caucasian group. Strong and significant associations between measures of fatness and metabolic risk were evident in Scottish South Asian adolescents.

Adjusted Indirect and Mixed Comparisons of Conservative Treatments for Hallux Valgus: A Systematic Review and Network Meta-Analysis.

Background: Hallux valgus (HV) deformity is a common, potentially debilitating deformity. And evidence with high-quality for the conservative treatments of HV deformity is still required.; AIMS: To compare the effects of different conservative treatments for hallux valgus deformity by using the method of network meta-analysis.; Study Design: A systematic review and network meta-analysis of randomized controlled trials identified by searching PubMed, EMBASE, MEDLINE, OVID, and CINAHL. The included studies should have the characteristics that: (1) participants with hallux valgus deformity of any age (2) conservative treatments (3) Reported the hallux valgus (HVA), the intermetatarsal angle (IMA), the score of the Visual Analog Scale, and the score of Foot Function Index.; Results: 11 studies were included in this review. The agreement between reviewers reached a kappa value of 0.75. The results of the network meta-analysis showed that a combination of exercise and toe separator, night splints, and dry needling are most likely to be the best choice for reducing the hallux valgus angle (HVA) and intermetatarsal angle, and toe separators (with or without exercise), dry needling, and manipulation (with or without ice treatment) have advantages in improving the subjective feeling of patients.; Conclusions: Multi-disciplinary conservative treatments have a great potential for hallux valgus deformity. More research with high-quality is needed to give a comprehensive and reasonable scheme of a holistic and long-term treatment protocol.