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Background. Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder with a high global incidence. Panax ginseng has been used to treat T2DM in traditional medicine, with previous in vitro, in vivo, and clinical trial studies demonstrating its efficacy. This study aimed to determine the mechanism of P. ginseng in treating T2DM by network pharmacology. Methods. The bioactive compounds of P. ginseng and corresponding targets of P. ginseng-T2DM were retrieved across multiple databases. The protein-protein interaction network was established using the STRING database and topological analysis helped identify the core target. Using the DAVID tool, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, we checked the binding of core targets and bioactive compounds using molecular docking. Results. The P. ginseng-T2DM networks mainly contained 22 bioactive compounds and 314 overlapping targets. The five most significant core targets were SRC, STAT3, MAPK1, AKT1, and PIK3R1. There were 244 GO terms and 95 KEGG pathways (adjusted p < 0.01) that were strongly correlated with diabetes-related signaling pathways, such as insulin resistance, the HIF-1 signaling pathway, the PI3K/Akt signaling pathway, the prolactin signaling pathway, the Rap1 signaling pathway, the Ras signaling pathway, the calcium signaling pathway, and the FoxO signaling pathway. Molecular docking results revealed that the top five core targets had a high binding affinity with the bioactive compounds of P. ginseng. Conclusion. The bioactive compounds and targets in P. ginseng ameliorate T2DM by regulating insulin resistance and multiple signaling pathways. [ABSTRACT FROM AUTHOR]

Multiple studies have demonstrated the effects of type 2 diabetes (T2D) on various human diseases; however, most of these were observational epidemiological studies that suffered from many potential biases including reported confounding and reverse causations. In this article, we investigated whether cancer and vascular disease can be affected by T2D-related traits, including fasting plasma glucose (FPG), 2-h postprandial glucose (2h-PG), and glycated hemoglobin A1c (HbA1c) levels, by using Mendelian randomization (MR). The summary statistics for FPG, 2h-PG, and HbA1c level were obtained through meta-analyses of large-scale genome-wide association studies that included data from 133,010 nondiabetic individuals from collaborating Meta-analysis of Glucose and Insulin Related Traits Consortium studies. Thereafter, based on the statistical assumptions for MR analyses, the most reliable approaches including inverse-variance-weighted (IVW), MR-Egger, MR-Egger with a simulation extrapolation (SIMEX), weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods were applied to identify traits affected by FPG, 2h-PG, and HbAlc. We found that coronary artery disease is affected by FPG, as per the IVW [log odds ratio (logOR): 0.21; P = 0.012], MR-Egger (SIMEX) (logOR: 0.22; P = 0.014), MR-PRESSO (logOR: 0.18; P = 0.045), and weighted median (logOR: 0.29; P < 0.001) methods but not as per the MR-Egger (logOR: 0.13; P = 0.426) approach. Furthermore, low-density lipoprotein cholesterol levels are affected by HbA1c, as per the IVW [beta (B): 0.23; P = 0.015), MR-Egger (B: 0.45; P = 0.046), MR-Egger (SIMEX) (B: 0.27; P = 0.007), MR-PRESSO (B; 0.14; P = 0.010), and the weighted median (B: 0.15; P = 0.012] methods. Further studies of the associated biological mechanisms are required to validate and understand the disease-specific differences identified in the TD2-related causal effects of each trait. [ABSTRACT FROM AUTHOR]

As a result of advances in sequencing technology, the role of gut microbiota in the mechanism of type-2 diabetes mellitus (T2DM) has been revealed. Studies showing wide distribution of microbiome throughout the human body, even in the blood, have motivated the investigation of the dynamics in gut microbiota across the humans. Particularly, extracellular vesicles (EVs), lipid bilayer structures secreted from the gut microbiota, have recently come into the spotlight because gut microbe-derived EVs affect glucose metabolism by inducing insulin resistance. Recently, intestine hyper-permeability linked to T2DM has also been associated with the interaction between gut microbes and leaky gut epithelium, which increases the uptake of macromolecules like lipopolysaccharide from the membranes of microbes leading to chronic inflammation. In this article, we firstly investigate the co-occurrence of stool microbes and microbe-derived EVs across serum and urine in human subjects (N = 284), showing the dynamics and stability of gut derived EVs. Stool EVs are intermediate, while the bacterial composition in both urine and serum EVs is distinct from the stool microbiome. The co-occurrence of microbes was compared between patients with T2DM (N = 29) and matched in healthy subjects (N = 145). Our results showed significantly higher correlations in patients with T2DM compared to healthy subjects across stool, serum, and urine, which could be interpreted as the dysfunction of intestinal permeability in T2DM. Therefore, the significant correlation of EVs might give insight into the pathophysiological mechanisms of T2DM, as well as the role of EVs as a biomarker in the intestinal permeability of T2DM. [ABSTRACT FROM AUTHOR]

Metformin, a first-line treatment for type 2 diabetes mellitus (T2DM), has recently been recognized for its pleotropic anti-proliferative, anti-cancer, and anti-aging effects. Contrary to the studies characterizing metformin effects in prostate cancer, little is known about these effects in BPH progression. With the Sample Cohort DB data during 2007 and 2017 from the Health Insurance Review and Assessment Service (HIRA) in South Korea, we investigated the preventative effect of metformin on BPH progression. The study population consisted of 211,648 BPH naïve patients that were diagnosed with BPH in 2009 and a follow-up occurrence of prostatectomy until 2017 that was defined as progression of BPH. These patients were divided into three treatment groups: without T2DM, T2DM without metformin, and T2DM with metformin. The hazard ratio in the T2DM with metformin group was 0.86 for prostatectomy compared to the group without T2DM (CI = 0.77–0.96, P value = 0.007) after adjusting for confounding factors such as age, comorbidity, residential area, level of hospital, and category of BPH medications. The T2DM with high-dose metformin group had a significantly lower risk of prostatectomy with hazard ratio of 0.76 (CI = 0.62–0.92, P value = 0.005) in stratified analysis. Our results suggest that metformin may improve BPH progression based on the reduced risk of prostatectomy, although T2DM effects on BPH were unclear. Future observational studies and prospective trials are needed to confirm the effects of metformin on BPH progression. [ABSTRACT FROM AUTHOR]

Objectives: To systematically review the effect of self-administered foot reflexology in patients with chronic health conditions. Methods: Electronic databases were searched for literature published from 1948 to January 2014. The databases included MEDLINE, EMBASE, the Cochrane Library, CINAHL, CNKI, J-STAGE, Koreamed, Kmbase, KISS, NDSL, KISTI, and OASIS. Key search terms were 'exp/relaxation therapy,' 'foot,' 'reflexology,' 'zone therapy,' and 'self.' All study designs were included. Two raters independently extracted data and assessed study quality by using the Cochrane risk of bias tool (for randomized controlled trials) and the risk of bias assessment tool for nonrandomized studies (for nonrandomized and before-and-after studies). A qualitative and descriptive analysis was performed because of the clinical diversity associated with chronic health conditions. Results: Of the 224 records assessed, 4 trials met the inclusion criteria: 3 nonrandomized controlled trials and 1 before-and-after study without comparison. Self-administered foot reflexology might have a positive effect in type 2 diabetes, but the low quality of the included study and the lack of adequately reported clinical outcomes obscure the results. Two studies of hypertensive patients and 1 study of patients with urinary incontinence showed that self-performed foot reflexology may exert a beneficial effect on lowering blood pressure and urinary incontinence; however, given the small sample size and the lack of any description of medications and other cointerventions, there was insufficient evidence to conclusively determine whether foot reflexology had any effect. Conclusions: The included studies on self-administered foot reflexology in patients with type 2 diabetes, hypertension, or urinary incontinence provided insufficient evidence to determine a treatment effect. Therefore, a well-designed, large-scale, and randomized controlled trial is needed to confirm the effect of self-administered foot reflexology for chronic conditions. [ABSTRACT FROM AUTHOR]