Effects of exercise interventions on brain-derived neurotrophic factor levels in overweight and obesity: A systematic review and meta-analysis.

Background: /Objective. An explosion in global obesity epidemic poses threats to the healthcare system by provoking risks of many debilitating diseases, including cognitive dysfunction. Physical activity has been shown to alleviate the deleterious effects of obesity-associated cognitive deficits across the lifespan. Given the strong neuroprotective role of brain-derived neurotrophic factor (BDNF) and exercise training as a known modulator for its elevation, this systematic review sought to examine the strength of the association between exercise and BDNF levels in healthy people with overweight and obesity. Methods: Six electronic databases (PubMed, MEDLINE, EMBASE, Web of Science, Ovid Nursing Database, and SPORTDiscus) were searched from their inceptions through December 2022. The primary outcome of interest was BDNF levels. Interventional studies (randomized and quasi-experimental) with English full text available were included. Risk of bias of the included studies was assessed using the Physiotherapy Evidence Database Scale. Data were extracted for meta-analyses by random-effects models. Results: Thirteen studies (n = 750), of which 69.2% (9/13) had low risk of bias, were included. In the meta-analysis, exercise interventions had no significant effect on resting BDNF levels (standardized mean difference: -0.30, 95% CI -0.80 to 0.21, P = 0.25). Subgroup analyses also indicated no effects of age and types of control groups being compared on moderating the association. Conclusion: To further inform the role of BDNF in obesity-related cognitive functioning, rigorous studies with larger samples of participants and raw data available were imperatively deserved.

Association between sonographically measured mesenteric fat thickness and brachial artery flow-mediated dilation in Chinese young male adults.

Objective To investigate the potential correlation between sonographically measured mesenteric fat thickness (MFT) and brachial artery flow-mediated dilation (FMD) in a sample of healthy Chinese male young adults. Methods Healthy male participants were recruited from Hong Kong Polytechnic University for this prospective observational study. The physical activity readiness questionnaire and ultrasound measurements of carotid intima media thickness were used to screen for clinically healthy subjects. MFT and brachial artery FMD were measured by ultrasound, and body mass index (BMI) was recorded. Results A total of 34 healthy male subjects, aged 19-26 years (mean ± SD BMI, 21.7 ± 3.2 kg/m2) were included. Pearson's correlation coefficient test showed that brachial artery FMD had a statistically significant inverse relationship with BMI and with Log (MFT). Further stepwise multiple linear regression analysis showed that Log (MFT), and not BMI, was an independent predictor of impaired brachial artery FMD. Conclusions Sonographic measurements of MFT were an independent predictor of brachial artery FMD in Chinese male young adults.

Diabetic nephropathy and endothelial dysfunction: Current and future therapies, and emerging of vascular imaging for preclinical renal-kinetic study.

An explosion in global epidemic of type 2 diabetes mellitus poses major rise in cases with vascular endothelial dysfunction ranging from micro- (retinopathy, nephropathy and neuropathy) to macro-vascular (atherosclerosis and cardiomyopathy) conditions. Functional destruction of endothelium is regarded as an early event that lays the groundwork for the development of renal microangiopathy and subsequent clinical manifestation of nephropathic symptoms. Recent research has shed some light on the molecular mechanisms of type 2 diabetes-associated comorbidity of endothelial dysfunction and nephropathy. Stemming from currently proposed endothelium-centered therapeutic strategies for diabetic nephropathy, this review highlighted some most exploited pathways that involve the intricate coordination of vasodilators, vasoconstrictors and vaso-modulatory molecules in the pathogenesis of diabetic nephropathy. We also emphasized the emerging roles of oxidative and epigenetic modifications of microvasculature as our prospective therapeutics for diabetic renal diseases. Finally, this review in particular addressed the potential use of multispectral optoacoustic tomography in real-time, minimally-invasive vascular imaging of small experimental animals for preclinical renal-kinetic drug trials.

Novel therapeutic potential in targeting microtubules by nanoparticle albumin-bound paclitaxel in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) shows low response to most conventional chemotherapies. To facilitate target identification for novel therapeutic development, we deployed gene expression profiling on 43 paired HCC tumors and adjacent non-tumoral liver, which is also considered as the pre-malignant liver lesion. In conjunction with ontology analysis, a major functional process found to play a role in the malignant transformation of HCC was microtubule-related cellular assembly. We further examined the potential use of microtubule targeting taxane drugs, including paclitaxel and docetaxel, and compared with findings to results from doxorubicin, a common chemotherapeutic agent used in HCC. Recent studies showed that drug delivery by nanoparticles have enhanced efficacy with reduced side effects. In this regard, the nanoparticle albumin-bound (nab)-paclitaxel was also examined. In a panel of HCC cell lines studied, a high sensitivity towards taxane drugs was generally found, although the effect from nab-paclitaxel was most profound. The nab-paclitaxel showed an effective IC50 dose at 15-fold lower than paclitaxel alone or the derivative analogue docetaxel, and ~450-fold less compared to doxorubicin. Flow cytometric analysis confirmed a cell cycle blockade at the G2/M phase and increased apoptosis following nab-paclitaxel treatment. In vivo animal studies also showed that nab-paclitaxel readily inhibited xenograft growth with less toxicity to host cells compared to other anti-microtubule drugs and doxorubicin. Gene silencing of the microtubule regulatory gene STMN1 by RNAi suggested a distinct synergistic effect in the combined treatment with nab-paclitaxel. Our findings in this study highly suggest that the microtubule assembly represents a promising therapeutic target development in HCC.