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Moreover, blockade of PI3KC1 by overexpression of dominant negative p85 subunit of PI3KC1 significantly attenuated Ang II-induced cardiac hypertrophy in normotensive rats. Taken together, these results demonstrate that both PI3KC1 and PI3KC3 are involved in Ang II-induced cardiac hypertrophy by different mechanisms. Activation of PI3KC1 impairs autophagy activity, leading to accumulation of mitochondrial ROS, and, hence, cardiac hypertrophy. In contrast, activation of PI3KC3 improves autophagy activity, thereby reducing mitochondrial ROS and leads to a protective effect on Ang II-induced cardiac hypertrophy.Traditional herbal patent medicine typically consists of multiple ingredients, making it challenging to supervise contamination by impurities and the improper use of raw materials. This study employed shotgun metabarcoding for the species identification of biological ingredients in traditional herbal patent medicine, Wuhu San. The five prescribed herbal materials found in Wuhu San were collected, and their reference sequences were obtained by traditional DNA barcoding using Sanger sequencing. Two lab-made and three commercial Wuhu San samples were collected, and a total of 37.14 Gb of shotgun sequencing data was obtained for these five samples using the Illumina sequencing platform. A total of 1,421,013 paired-end reads were enriched for the Internal Transcribed Spacer 2 (ITS2), psbA and trnH intergenic spacer region (psbA-trnH), maturase k (matK), and ribulose-1, 5-bisphosphate carboxylase (rbcL) regions. Furthermore, 80, 11, 9, and 8 operational taxonomic units were obtained for the ITS2, psbA-trnH, matK, as medicinal material underwent extensive processing. In addition, the Saposhnikovia divaricata adulterant was detected in all the commercial samples, while 24 fungal genera, including Aspergillus, were identified in both the lab-made and commercial samples. This study showed that shotgun metabarcoding provided alternative strategy and technical means for identifying prescribed ingredients in traditional herbal patent medicine and displayed the potential to effectively complement traditional methods.Metformin is widely used in the treatment of Type 2 Diabetes Mellitus (T2DM). However, it is known to have beneficial effects in many other conditions, including obesity and cancer. In this study, we aimed to investigate the metabolic effect of metformin in T2DM and its impact on obesity. A mass spectrometry (MS)-based metabolomics approach was used to analyze samples from two cohorts, including healthy lean and obese control, and lean as well as obese T2DM patients on metformin regimen in the last 6 months. The results show a clear group separation and sample clustering between the study groups due to both T2DM and metformin administration. Seventy-one metabolites were dysregulated in diabetic obese patients (30 up-regulated and 41 down-regulated), and their levels were unchanged with metformin administration. However, 30 metabolites were dysregulated (21 were up-regulated and 9 were down-regulated) and then restored to obese control levels by metformin administration in obese diabetic patients. Copanlisib concentration Furthermore, in obese diabetic patients, the level of 10 metabolites was dysregulated only after metformin administration. Most of these dysregulated metabolites were dipeptides, aliphatic amino acids, nucleic acid derivatives, and urea cycle components. The metabolic pattern of 62 metabolites was persistent, and their levels were affected by neither T2DM nor metformin in obesity. Interestingly, 9 metabolites were significantly dysregulated between lean and obese cohorts due to T2DM and metformin regardless of the obesity status. These include arginine, citrulline, guanidoacetic acid, proline, alanine, taurine, 5-hydroxyindoleacetic acid, and 5-hydroxymethyluracil. Understanding the metabolic alterations taking place upon metformin treatment would shed light on possible molecular targets of metformin, especially in conditions like T2DM and obesity.Background Metformin has anti-inflammatory property and reduces the risk of varicose vein in our previous study. Aim To investigate the risk of hemorrhoid, another common disease involving the hemorrhoidal venous plexus, in ever vs. never users of metformin in patients with type 2 diabetes mellitus. Methods This is a population-based retrospective cohort study. Patients with new-onset type 2 diabetes mellitus during 1999-2005 were enrolled from Taiwan's National Health Insurance. All patients who were alive on January 1, 2006 were followed up until December 31, 2011. Analyses were conducted in both an unmatched cohort of 152,347 ever users and 19,523 never users and in 19,498 propensity score (PS)-matched pairs of ever and never users. Traditional Cox regression and Cox regression incorporated with the inverse probability of treatment weighting (IPTW) using the PS were used to estimate hazard ratios. Results New-onset hemorrhoid was diagnosed in 8,211 ever users and 2025 never users in the unmatched cohort and in 1,089 ever users and 2022 never users in the matched cohort. The hazard ratio for ever vs. never users derived from the traditional Cox regression was 0.464 (95% confidence interval 0.440-0.488) in the unmatched cohort; and was 0.488 (0.453-0.525) in the matched cohort. In the IPTW models, the hazard ratio was 0.464 (0.442-0.487) in the unmatched cohort and was 0.492 (0.457-0.530) in the matched cohort. A dose-response pattern was observed while comparing the tertiles of cumulative duration, cumulative dose and defined daily dose of metformin therapy to never users in all analyses. A risk reduction of approximately 40-50% was consistently observed in various sensitivity analyses. Conclusion Chronic therapy with metformin in patients with type 2 diabetes mellitus is associated with a lower risk of hemorrhoid.Antimicrobial stewardship (AMS) program promotes the judicious use of antimicrobials. Hence, this study was conducted to analyze the impact of stewardship on the prescribing pattern of cefuroxime injection among the surgeons as perioperative antimicrobial prophylaxis (PAP). This study was conducted retrospectively in Malaysia. Various outcomes were measured including cefuroxime usage, compliance with the guidelines, surgical site infections, and cost savings. A total of 1,601 patients were recruited in the study. In terms of usage, the total defined daily dose (DDD) prior to the intervention was 202 DDD/100 procedures compared to that after intervention which was 144 DDD/100 procedures (p less then 0.05). On the other hand, the excessively long administration of PAP dropped from 94.4 to 30.3% (p less then 0.001). Focusing on the compliance with the newly developed local guidelines, it has increased from 53 to 94.3% after the interventions were made (p less then 0.001), whereas the rate of surgical site infections was reduced from 17.
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