Effect of Exercise on the Cognitive Function of Older Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Background: Aging and type 2 diabetes mellitus (T2DM) are important risk factors for the development of cognitive deterioration and dementia. The objective of this research was to investigate the effects of an exercise intervention on cognitive function in older T2DM patients. Methods: Eight literature databases (PubMed, EBSCO, Scopus, Embase, The Cochrane Library, Web of Science, Ovid, and ProQuest) were searched from inception to 20 January 2022. The researchers examined randomized controlled trials (RCTs) that evaluated the impact of exercise on the cognitive performance of older T2DM patients. The Cochrane risk-of-bias tool (ROB 2) for RCTs was used to assess each study. The quality of evidence was assessed using the GRADE (grading of recommendations, assessment, development, and evaluations) approach. The mini-mental state examination (MMSE), Modified MMSE (3MSE), and Montreal cognitive assessment (MoCA) were used to evaluate the cognitive outcomes. We performed a subgroup analysis with stratification according to exercise intervention modality, duration, and cognitive impairment. Results: Five trials were eligible, with a total of 738 T2DM patients. The combined findings revealed that exercise improved global cognitive function significantly (standardized mean difference: 1.34, 95% confidence interval: 0.23-2.44, p < 0.01). The effect of exercise on global cognitive performance was not significantly influenced by intervention modality, intervention duration, or cognitive impairment in the sub-group analysis (p > 0.05). In the studies that were included, no relevant adverse events were reported. Conclusion: Exercise is beneficial in improving global cognitive function in older adults with T2DM. Studies with bigger sample sizes and higher quality are additionally expected to draw more definite conclusions. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/#recordDetails], identifier [CRD42022296049].

Efficacy and Safety of Blood Flow Restriction Training in Patients With Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the efficacy and safety of blood flow restriction training (BFRT) in the treatment of patients with knee osteoarthritis (OA). METHOD: Seven electronic databases were searched to identify trials comparing BFRT and conventional resistance training in a population with knee OA. Studies were selected according to the inclusion and exclusion criteria. Standardized mean differences (SMDs) or risk ratios (RRs) with 95% confidence intervals (95% CIs) were calculated to compare outcome measures of the groups. The methodologic quality of selected studies and the quality of evidence were evaluated for included studies. RESULTS: A total of 5 studies were included in this meta-analysis, with very low to moderate risk of bias. The pooled results showed no significant difference between BFRT and conventional resistance training for knee OA, including pain (SMD -0.04 [95% CI -0.31, 0.24], P = 0.79), physical function performance (SMD 0.12 [95% CI -0.55, 0.78], P = 0.73), self-reported function (SMD 0.14 [95% CI -0.24, 0.52], P = 0.48), and adverse events (RR 0.45 [95% CI 0.20, 1.01], P = 0.05). In subgroup analysis, BFRT had a lower incidence of adverse events when compared with high-load resistance training (HLRT). CONCLUSION: Data from pooled studies showed that BFRT may not have greater efficacy for treating patients with knee OA, and it is less likely to have a higher risk of adverse events. However, limited evidence supports the idea that BFRT is likely safer than HLRT. More evidence with high quality is needed in further research on efficacy and safety.

Hyperactive reactive oxygen species impair function of porcine Sertoli cells via suppression of surface protein ITGB1 and connexin-43.

Gap junctions regulate intercellular communication between Sertoli cells and germ cells in male testes and play vital functions in spermatogenesis. Many factors in animal breeding and husbandry can induce oxidative stress, which can impair the testis microenvironment and male animal fertility. However, the underlying mechanisms are largely unknown. Recently, we identified that androgen signals promote the expression of connexin-43 (Cx43), a key component of gap junctions, to regulate spermatogenesis. Thus, we asked whether hyperactive reactive oxygen species (ROS) can impair gap junctions by interfering with Cx43 in porcine testes. Using a porcine Sertoli cell in vitro system, we found that hyperactive ROS caused extensive apoptosis in Sertoli cells, remarkable decrease in Cx43 expression, and failed maintenance of co-cultured spermatogonial stem cells (SSCs), indicating that ROS impaired the function of Sertoli cells and promoted loss of SSCs. This observation provides a possible mechanism for the impact of ROS on fertility of male animals.

Elucidating cytochrome C release from mitochondria: insights from an in silico three-dimensional model.

Mitochondrial regulation of apoptosis depends on the programmed release of proapoptotic proteins such as cytochrome c (Cyt c) through the outer mitochondrial membrane (OMM). Although a few key processes involved in this release have been identified, including the liberation of inner membrane-bound Cyt c and formation of diffusible pores on the OMM, other details like the transport of Cyt c within complex mitochondrial compartments, e.g., the cristae and crista junctions, are not yet fully understood (to our knowledge). In particular, a remodeling of the inner mitochondrial membrane accompanying apoptosis seen in a few studies, in which crista junctions widen, has been hypothesized to be a necessary step in the Cyt c release. Using a three-dimensional spatial modeling of mitochondrial crista and the crista junction, model simulations and analysis illustrated how the interplay among solubilization of Cyt c, fast diffusion of Cyt c, and OMM permeabilization gives rise to the observed experimental release profile. Importantly, the widening of the crista junction was found to have a negligible effect on the transport of free Cyt c from cristae. Finally, model simulations showed that increasing the fraction of free/loosely-bound Cyt c can sensitize the cell to apoptotic stimuli in a threshold manner, which may explain increased sensitivity to cell death associated with aging.