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Among its many biological roles, fibroblast growth factor 2 (FGF2) protects the heart from dysfunction and damage associated with an ischemic attack. Our laboratory demonstrated that its protection against myocardial dysfunction occurs by the low molecular weight (LMW) isoform of FGF2, while the high molecular weight (HMW) isoforms are associated with a worsening in post-ischemic recovery of cardiac function. LMW FGF2-mediated cardioprotection is facilitated by activation of multiple kinases, including PKCalpha, PKCepsilon, and ERK, and inhibition of p38 and JNK.
Yet, the substrates of those kinases associated with LMW FGF2-induced cardioprotection against myocardial dysfunction remain to be elucidated.
To identify substrates in LMW FGF2 improvement of post-ischemic cardiac function, mouse hearts expressing only LMW FGF2 were subjected to ischemia-reperfusion (I/R) injury and analyzed by a mass spectrometry (MS)-based quantitative phosphoproteomic strategy. MS analysis identified 50 phosphorylation siteulatory changes in SR proteins essential for recovery from I/R injury, and thereby protects the heart from post-ischemic cardiac dysfunction.
The findings indicate that LMW FGF2 modulates intracellular calcium handling/cycling via regulatory changes in SR proteins essential for recovery from I/R injury, and thereby protects the heart from post-ischemic cardiac dysfunction.The US Food and Drug Administration convened a workshop to discuss clinical trial design challenges and considerations related to the treatment of nontuberculous mycobacterial pulmonary disease, to include topics such as clinical trial end points, duration, and populations. The clinicians participating in the meeting provide here their interpretation of the discussion, which included US Food and Drug Administration and industry representatives. The treatment of nontuberculous mycobacterial pulmonary disease typically includes multiple antibiotics for a prolonged period and can be difficult to tolerate; there is a great need for new treatment options. Most individuals have a microbiologic response to therapy, but data correlating decreasing bacillary load with patient-reported outcomes or measured functional improvement are lacking. Accordingly, trial designs for new therapeutic agents should incorporate both microbiologic and clinical outcome measures and select appropriate study candidates with capacity for measurable change of such outcome measures. The need for shorter study designs, early primary end points, and placebo control arms was highlighted during the workshop.
Long-term testosterone replacement therapy (TRT) increases muscle mass in elderly men with subnormal testosterone levels. However, the molecular mechanisms underlying this effect of TRT on protein balance in human skeletal muscle in vivo remain to be established.
Here, we examined skeletal muscle biopsies obtained before and 24-h after the last dose of treatment with either testosterone gel (n = 12) or placebo (n = 13) for 6 months in aging men with subnormal bioavailable testosterone levels. The placebo-controlled, testosterone-induced changes (β-coefficients) in mRNA levels, protein expression and phosphorylation were examined by quantitative real-time PCR and western blotting.
Long-term TRT increased muscle mass by β = 1.6 kg (p = 0.01) but had no significant effect on mRNA levels of genes involved in myostatin/activin/SMAD or IGF1/FOXO3 signalling, muscle-specific E3-ubiquitin ligases, upstream transcription factors (MEF2C, PPARGC1A-4) or myogenic factors. However, TRT caused a sustained decrease inmuscle-specific E3-ubiquitin ligases.
Duodenal endoscopic submucosal dissection (ESD) is considered technically challenging and has a high risk of adverse events. However, we recently made some progress with the ESD technique and device by introducing 2 features a water pressure (WP) method and a second-generation ESD knife (DualKnife) with a water jet function (DualKnife J). The present study aimed to assess whether these changes improved the clinical outcomes of duodenal ESD.
This was a retrospective observational study. Among all patients who underwent ESD for superficial duodenal epithelial tumors from June 2010 to December 2018, patients in whom a single expert performed the procedure were included in this study. Various factors, including the use of the WP method and ESD devices (DualKnife or DualKnife J) and the treatment phase (early, mid, and late), were analyzed to determine whether they were associated with intraprocedural perforation and procedure time. Treatment phase was assigned by dividing the study population equally into 3 subgroups according to the treatment phase.
The procedure time was significantly shorter, and the proportion of patients with intraprocedural perforations was the lowest in the late phase. Multivariate analysis of the use of the WP method revealed that it significantly decreased the intraprocedural perforation rate (odds ratio, 0.39; 95% confidence interval, 0.16-0.96), and analysis of the use of both the WP method (β coefficient,-0.40; P< .01) and the DualKnife J (β coefficient,-0.10; P= .032) revealed they were independently and negatively correlated with procedure time.
The present study reveals that the WP method significantly reduced the intraprocedural perforation rate and that both the WP method and the DualKnife J significantly shortened procedure times for duodenal ESD.
The present study reveals that the WP method significantly reduced the intraprocedural perforation rate and that both the WP method and the DualKnife J significantly shortened procedure times for duodenal ESD.
To better understand the physical and psychosocial components of female sexual dysfunction (FSD) among women undergoing radical cystectomy (RC) for bladder cancer (BCa).
We conducted semistructured individual interviews and a focus group with pre- and post-RC female patients and their partners regarding the impact of RC on sexual health and psychosocial wellbeing. Themes were inductively identified by 2 independent coders and subsequently organized into themes and subthemes using qualitative description and constant comparison.
In the preoperative cohort, 6 women and 1 partner participated (50% contact rate, 75% participation rate). CHS828 inhibitor In the postoperative cohort, 16 women and 2 partners participated (61% contact rate, 64% participation rate). Major themes that emerged in interviews with both cohorts included concerns about changes to body image, the psychological impact of BCa diagnosis and treatment, concerns about the impact of RC on sexual function, and inadequacies in provider-led sexual health counseling.
Website: https://www.selleckchem.com/products/gmx1778-chs828.html
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