Mesenchymal stem cells-derived exosomal miR-24-3p ameliorates non-alcohol fatty liver disease by targeting Keap-1.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide with ill-defined etiology and pathogenesis, and no approved effective therapy is presently available. Exosome-dependent intercellular communication has been identified as a potential signaling involved in tissue repair. Unfortunately, the exact influence and underlying mechanism of mesenchymal stem cells (MSCs)-derived exosome (Exo) in modulating fatty liver have not been well determined. Here in our study, in vitro results initially showed that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs)-derived Exo treatment significantly suppressed lipid accumulation, reactive oxygen species (ROS) generation and inflammatory response in palmitate (PA)-stimulated mouse hepatocytes. Consistently, MSCs-derived Exo administration strongly ameliorated metabolic disorders, hepatic dysfunction and steatosis in high fat diet (HFD)-induced mouse model with NAFLD. Furthermore, Exo derived from MSCs significantly alleviated hepatic lipid metabolism disturbance, inflammation and oxidative stress induced by HFD. Exo treatment resulted in a stronger increase in miR-24-3p expression in hepatocytes. Reducing miR-24-3p in MSCs markedly abrogated the protective effects of Exo in hepatocytes under PA stimulation. Mechanistically, miR-24-3p directly targeted Kelch-like ECH-associated protein 1 (Keap-1), and suppressed its expression. In addition, the effects of MSCs-derived exosomal miR-24-3p to restrain lipid accumulation, ROS generation and inflammation in vitro were largely Keap-1 dependent via Keap-1 depression. Collectively, our study demonstrated that MSCs-derived exosomal miR-24-3p had hepaprotective effects through targeting Keap-1 signaling, providing a potential therapeutic value for NAFLD treatment.

Exercise-Mediated Alteration of miR-192-5p Is Associated with Cognitive Improvement in Alzheimer's Disease.

INTRODUCTION: Physical exercise is an important component of managing Alzheimer's disease (AD). miRNAs can be modulated by exercise intervention. OBJECTIVE: The study explored the involvement and potential mechanism of miR-192-5p in the protective effect of physical exercise on AD. METHODS: Ninety AD patients were enrolled, in which 45 cases accepted cycling training for continuous 3 months. The expression changes of miR-192-5p before and after exercise were analyzed by reverse transcription-quantitative PCR. 8-month-old APP/PS1 double Tg mice were used as the AD animal model. Mice in the voluntary exercise (VE) group received VE for 4 weeks. Morris water maze (MWM) test was used to evaluate the learning and memory function. Enzyme-linked immunosorbent assay was used to calculate the level of IL-1ß, IL-6, and TNF-α. RESULTS: AD patients showed elevated MMSE scores, decreased ADAS-cog and NPI-Q scores after 3 months of exercise. miR-192-5p was downregulated in the serum of AD patients and correlated with the levels of MMSE score, ADAS-cog, and NPI-Q score. A positive association was detected between serum miR-192-5p with TNF-α, IL-6, and IL-1ß levels. MiR-192-5p is downregulated in the hippocampus tissues of mice after VE. Overexpression of miR-192-5p reversed the neuroprotective effect of exercise on AD in mice and promoted the inflammatory response of AD mice. CONCLUSION: MiR-192-5p can be modulated by the exercise intervention and involved in the protective effect of exercise on AD.

The Role of Probiotics in Managing Glucose Homeostasis in Adults with Prediabetes: A Systematic Review and Meta-Analysis.

Methods: The Preferred Reporting Items for Systematic Reviews and Analysis checklist was used. A comprehensive literature search of the PubMed, Embase, and Cochrane Library databases was conducted through August 2022 to assess the impact of probiotics on blood glucose, lipid, and inflammatory markers in adults with prediabetes. Data were pooled using a random effects model and were expressed as standardized mean differences (SMDs) and 95% confidence interval (CI). Heterogeneity was evaluated and quantified as I2. Results: Seven publications with a total of 550 patients were included in the meta-analysis. Probiotics were found to significantly reduce the levels of glycosylated hemoglobin (HbA1c) (SMD -0.44; 95% CI -0.84, -0.05; p = 0.03; I2 = 76.13%, p < 0.001) and homeostatic model assessment of insulin resistance (HOMA-IR) (SMD -0.27; 95% CI -0.45, -0.09; p < 0.001; I2 = 0.50%, p = 0.36) and improve the levels of high-density lipoprotein cholesterol (HDL) (SMD -8.94; 95% CI -14.91, -2.97; p = 0.003; I2 = 80.24%, p < 0.001), when compared to the placebo group. However, no significant difference was observed in fasting blood glucose, insulin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, interleukin-6, tumor necrosis factor-α, and body mass index. Subgroup analyses showed that probiotics significantly reduced HbA1c in adults with prediabetes in Oceania, intervention duration of ≥3 months, and sample size <30. Conclusions: Collectively, our meta-analysis revealed that probiotics had a significant impact on reducing the levels of HbA1c and HOMA-IR and improving the level of HDL in adults with prediabetes, which indicated a potential role in regulating blood glucose homeostasis. However, given the limited number of studies included in this analysis and the potential for bias, further large-scale, higher-quality randomized controlled trials are needed to confirm these findings. This trial is registered with CRD42022358379.

Uterine leiomyoma causes an increase in systolic blood pressure: a two-sample Mendelian randomization study.

Objectives: Hypertension and hypertensive disorders of pregnancy (HDP) are common diseases in women at different stages, which affect women's physical and mental health, and the impact of the latter on the offspring cannot not be ignored. Observational studies have investigated the correlation between uterine leiomyoma (UL) and the above conditions, but the relationship remains unclear. In this study, we employed two-sample Mendelian randomization (MR) analysis to assess the association between UL and hypertension, HDP, as well as blood pressure. Methods: We collected genetic association data of UL (35,474 cases), hypertension (129,909 cases), HDP (gestational hypertension with 8,502 cases, pre-eclampsia with 6,663 cases and eclampsia with 452cases), systolic blood pressure (SBP) and diastolic blood pressure (DBP) (both 757,601 participants) from published available genome-wide association studies (GWAS). The single nucleotide polymorphisms (SNPs) associated with UL phenotype were used as instrumental variables, and hypertension, three sub-types of HDP, SBP and DBP were used as outcomes. The inverse-variance weighted (IVW) method was employed as the primary method of causal inference. Heterogeneity was assessed using Cochran's Q test, and sensitivity analyses were conducted using MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) tests to evaluate the pleiotropy of instrumental variables. PhenoScanner search was used to remove confounding SNP. Robustness and reliability of the results were assessed using methods such as the weighted median and weighted mode. Results: The IVW analysis revealed a positive correlation between genetically predicted UL and SBP [odds ratio (OR)= 1.67, 95% confidence interval (CI):1.24~2.25, P = 0.0007], and no statistical association was found between UL and hypertension, HDP, or DBP. The MR-Egger regression suggested that the above causal relationships were not affected by horizontal pleiotropy. The weighted median method and weighted model produced similar results to the IVW. Conclusion: Based on large-scale population GWAS data, our MR analysis suggested a causal relationship between UL and SBP. Therefore, women with UL, especially pregnant women, should pay attention to monitoring their blood pressure levels. For patients with hypertension who already have UL, interventions for UL may serve as potential therapeutic methods for managing blood pressure.

Yunmen (LU 2) combined with neck-seven-acupoint acupuncture for arm numbness caused by cervical spondylotic radiculopathy: A case report.

RATIONALE: Cervical spondylotic radiculopathy (CSR) is a common sensory, motor, and reflex disorder. Numbness, a common subjective symptom of CSR, lacks objective quantitative indicators and recognized effective treatments, but is also difficult to recover from. We present a case report describing a traditional acupuncture treatment for CSR, utilizing a special acupuncture method and point, namely the Yunmen point. PATIENT CONCERNS: A 40-year-old woman presented with unilateral arm numbness caused by CSR. DIAGNOSES: A diagnosis of CSR was made in the orthopedic department of a local hospital. INTERVENTIONS: We attempted acupuncture at the Yunmen (LU 2) acupoint combined with neck-seven-acupoint under computed tomographic guidance. OUTCOMES: After 10 times treatment sessions, the patient no longer experienced weakness, coldness, or numbness in the affected upper limb. In addition, the stiffness in the neck and shoulders was reduced. On physical examination, the patient's left brachial plexus traction test was negative; reassessment of the CSR-20-point score scale showed a perfect score, and the visual analog scale score was 0. LESSONS: Our report indicates that acupuncture at the LU 2 acupoint combined with neck-seven-acupoint is effective in treating numbness and coldness of the arm, and other neurological symptoms caused by cervical spondylosis. Moreover, with the appropriate acupuncture technique, the risk of acupuncture at the LU 2 acupoint can be minimized.

Medicated thread moxibustion for alopecia areata: A case report.

RATIONALE: According to the literature reports and clinical studies on alopecia areata (AA) from 2008 to 2018, most clinical treatments have been oral drugs and external ointments. At present, systemic immunosuppressive therapy has been widely used in AA, but there are various side effects such as elevated liver enzymes, gastrointestinal discomfort, poor drug compliance, and repeated illness. We present a case report describing a traditional medicine treatment for AA that uses an ethnic therapy of Zhuang medicine, a kind of Traditional Chinese Medicine, namely, medicated thread moxibustion. PATIENT CONCERNS: A 36-year-old man endured AA after going through a family misfortune. Half a year ago, his father passed away suddenly. Since then, he suffered continuous anguish, alcoholism and hair loss, especially in the past 2 months. A coin-shaped area of hair loss began to appear at the top of his head and gradually expanded to the surrounding region. DIAGNOSES: A diagnosis of AA was made in the dermatology department of a local hospital. INTERVENTIONS: The patient was treated with the medicated thread moxibustion method of Traditional Zhuang Medicine at the Kuihua (special points of Zhuang medicine), Zusanli (ST 36), Xuehai (SP 10), Baihui (DU 20), and Taichong (LR 3) points every other day for 4 weeks. OUTCOMES: The area of hair loss showed slight improvement after 1 week of treatment. Only just a sprinkling of wooly hairs, whose color and thickness were similar to those of fine facial hairs, began to emerge sporadically from the follicles; they could be seen only in a bright light. When the patient saw the obvious curative effect, we continued the treatment for 2 weeks with the patient's consent. Three weeks later, the patchy AA area was covered with small cotton-like hairs of different lengths and uneven colors. LESSONS: The medicated thread moxibustion method of Zhuang medicine can be an effective alternative treatment in patients with AA.