Higher-dose sitagliptin and the risk of congestive heart failure in older adults with CKD

Background and objectives Sitagliptin, a dipeptidylpeptidase-4 inhibitor, is commonlyprescribed to patientswith type 2 diabetes. As this drug is primarily eliminated by the kidney, a reduced dose is recommended for patients with CKD. Some evidence suggests that sitagliptin is associated with a higher risk of congestive heart failure, particularly at higher doses.Wecompare the 1-year risk of death or hospitalizationwith congestive heart failure in patients with CKD newly prescribed sitagliptin at \u3c50 versus ≤50 mg/d. Design, setting, participants, & measurements This population-based cohort study included older adults (\u3e66 years) with type 2 diabetes and an eGFR\u3c45 ml/min per 1.73 m2 (but not receiving dialysis) who were newly prescribed sitagliptin between 2010 and 2017 in Ontario, Canada. We used inverse probability of treatment weighting on the basis of propensity scores to balance baseline characteristics. The primary composite outcome was death or hospitalization with congestive heart failure. Secondary outcomes included hospitalization with pancreatitis or hypoglycemia, all-cause hospitalization, and glycemic control. Weighted hazard ratios were obtained using Cox proportional hazards regression, and 95%confidence intervalswere obtained using bootstrap variance estimators. Results Of 9215 patients, 6518 started sitagliptin at \u3e50 mg/d, and 2697 started sitagliptin at ≤50 mg/d. The 1-year risk of death or hospitalization with congestive heart failure did not differ significantly between groups (79 versus 126 events per 1000 person-years; weighted hazard ratio, 0.88; 95% confidence interval, 0.67 to 1.14); hospitalization with pancreatitis (weighted hazard ratio, 0.98; 95% confidence interval, 0.32 to 3.03) and hypoglycemia (weighted hazard ratio, 1.10; 95% confidence interval, 0.64 to 1.90) also did not differ significantly between groups. Patients starting sitagliptin at \u3e50 mg/d had lower mean glycated hemoglobin concentrations (weighted between-group difference, 20.12%; 95% confidence interval, 20.19 to 20.06) and a lower risk of allcause hospitalization (weighted hazard ratio, 0.81; 95% confidence interval, 0.66 to 0.98). Conclusions The risk of death or congestive heart failure was not higher in older adults with CKD starting sitagliptin at \u3e50 versus ≤50 mg/d

Role of SIRT2 in regulating the dexamethasone-activated autophagy pathway in skeletal muscle atrophy

The proteolytic autophagy system is involved in a major regulatory pathway in dexamethasone (Dex)-induced muscle atrophy. Sirtuin 2 (SIRT2) is known to participate in modulating autophagy signaling, exerting effects in skeletal muscle atrophy. We aimed to determine the effects of SIRT2 on autophagy in Dex-induced myoatrophy. Mice were randomly divided into the normal, Dex, and sirtinol groups. C2C12 cells were differentiated into myotubes and transfected with short hairpin (sh)-Sirt2-green fluorescent protein (GFP) or Sirt2-GFP lentivirus. To evaluate the mass and function of skeletal muscles, we measured the myofiber cross-sectional area, myotube size, gastrocnemius muscle wet weight/body weight ratio (%), and time-to-exhaustion. The SIRT2, myosin heavy chain (MyHC), LC3, and Beclin-1 expression levels were detected by western blotting and quantitative reverse transcription-polymerase chain reaction. Inhibition of SIRT2 markedly attenuated the muscle mass and endurance capacity. The same phenotype was observed in Sirt2-shRNA-treated myotubes, as evidenced by their decreased size. Conversely, SIRT2 overexpression alleviated Dex-induced myoatrophy in vitro. Moreover, SIRT2 negatively regulated the expression of the LC3b and Beclin-1 in skeletal muscles. These findings suggested that SIRT2 activation protects myotubes against Dex-induced atrophy through the inhibition of the autophagy system; this phenomenon may potentially serve as a target for treating glucocorticoid-induced myopathy.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Association between SHMT1 gene promoter methylation and ischemic stroke

Objective To explore the relationship between serine hydroxymethyltransferase (SHMT1) gene methylation and ischemic stroke patients. Methods The quantitative methylation-specific PCR was used to measure the level of SHMT1 promoter methylation in 290 healthy control individuals and 141 ischemic stroke patients. Results The results showed that the SHMT1 methylation level in the stroke group was 24.87(16.97~35.46), higher than that in the control group 6.58(2.43~15.14) (P＜0.05). After adjusting for relevant risk factors, SHMT1 methylation was a risk factor for stroke(OR=1.051, 95% CI= 1.034~1.068). Area under the curve was 0.804, 95% CI=0.760~0.849(P＜0.01). The level of uric acid was associated with SHMT1 methylation in the control group(rs=0.17, P＜0.01), and the level of TG was associated with SHMT1 methylation in the stroke group(rs=0.18, P＜0.05). SHMT1 methylation expression was negatively correlated with mRNA expression(r=-0.472, P＜0.01). Conclusions The SHMT1 gene is more methylated and results in low expression in ischemic stroke patients, so SHMT1 hypermethylation is a risk factor for stroke

Analysis of microbial community and biodeterioration of maritime cultural relics (ironware, porcelain, axes, hull wood) from the Nanhai No. 1 shipwreck

Abstract Purpose Maritime cultural relics from the Nanhai No. 1 shipwreck were immersed in a buffer to maintain stability. To better monitor the changes in the composition of microorganisms in the buffer and, thus, prevent the damage to artifacts caused by harmful microorganisms. Methods In September and November 2019, we conducted high-throughput sequencing of water samples from four types of maritime cultural relics (ironware, porcelain, axe, and hull wood) to reveal the composition and changes in microbial communities. In addition, we isolated culturable microorganisms and conducted biocide sensitivity tests and lignin and cellulose degradation tests. Results Visible microbial colonization was observed in the water samples collected from the buffer solutions of ironware, porcelain, axe, and hull wood of the Nanhai No. 1 shipwreck; additionally, apparent differences in the composition of microorganisms in the water samples collected from different cultural relics and different collection times of the same cultural relics were noted. Few species of bacteria and fungi from the microbial community observed in the maritime cultural relics were cultured, and it was noted that various biocides had certain inhibitory effects on them. Some dominant strains had lignin and cellulose degradation abilities and could only grow under specific environmental conditions. Conclusion We found apparent differences in the composition of microorganisms obtained from different cultural relics and different collection times of the same cultural relics. This study can provide data support for better protection of maritime cultural relics obtained from the Nanhai No. 1 shipwreck and provide a theoretical basis for the biological protection of other maritime cultural relics

Therapeutic potential of tumor treating fields for malignant brain tumors

Abstract Background Malignant brain tumors are among the most threatening diseases of the central nervous system, and despite increasingly updated treatments, the prognosis has not been improved. Tumor treating fields (TTFields) are an emerging approach in cancer treatment using intermediate‐frequency and low‐intensity electric field and can lead to the development of novel therapeutic options. Recent Findings A series of biological processes induced by TTFields to exert anti‐cancer effects have been identified. Recent studies have shown that TTFields can alter the bioelectrical state of macromolecules and organelles involved in cancer biology. Massive alterations in cancer cell proteomics and transcriptomics caused by TTFields were related to cell biological processes as well as multiple organelle structures and activities. This review addresses the mechanisms of TTFields and recent advances in the application of TTFields therapy in malignant brain tumors, especially in glioblastoma (GBM). Conclusions As a novel therapeutic strategy, TTFields have shown promising results in many clinical trials, especially in GBM, and continue to evolve. A growing number of patients with malignant brain tumors are being enrolled in ongoing clinical studies demonstrating that TTFields‐based combination therapies can improve treatment outcomes