Acute ischemic stroke is a devastating disease with very limited therapeutics. Growing appreciation of dysregulated autophagy contributes to the progression of brain ischemic injury, making it to be an appealing intervention target. In terms of its well-characterized consequences, the signal molecules required for autophagy activation are rather poorly defined. Here, we found the induction of chloride channel-3 (ClC-3) directly activated autophagy, which played an important role in limiting cerebral ischemia/reperfusion (I/R) injury. Further mechanism exploration discovered that the up-regulation of ClC-3 was critical for the interaction of Beclin1 and Vps34. After ClC-3 knockdown using adeno-associated virus vectors in vivo, the autophagy activation was partially inhibited through disrupting the formation of Beclin1 and Vps34 complex. Consistent with these observations, ClC-3 knockdown could also significantly aggravated cerebral I/R injury through suppressing autophagy in vivo, which further confirmed the neuroprotective roles of ClC-3. Collectively, we provided an novel evidence for ClC-3 serving as a crucial regulator of autophagy; and our results indicated that the induction of ClC-3 may serve as a self-protective mechanism against cerebral I/R injury.GSK-126 is recognized as an inhibitor of enhancer of zeste homolog-2 (EZH2) activity. Because of its inhibition of EZH2 activation, GSK-126 is considered a potential anti-tumor drug. EZH2 is a histone methyltransferase that catalyzes histone 3 tri-methylation at lysine 27 (H3K27me3), resulting in gene silencing. A previous report showed that decreased H3K27me3 levels in the hippocampus may promote seizure susceptibility, possibly restricting the clinical application of GSK-126. The role of GSK-126 in seizure susceptibility was investigated in this study. We first determined a critical concentration of pentamethazol (PTZ) under which mice exhibit no seizures. We then found that mice pretreated with GSK-126 and injected with the same concentration of PTZ experienced marked convulsions. Peripheral injections of GSK-126 decreased H3K27me3 levels in the hippocampus of mice, while some seizure-related genes (Oasl1, Sox7, armcx5, Ncx3, etc.) were found to be differentially expressed in the hippocampus of those mice . These differences in the expression levels might reflect the crucial role of these genes and related pathways in the promotion of seizure susceptibility. PIN1 inhibitor API-1 manufacturer Our results suggest that GSK-126 promotes seizure susceptibility due to its role as an EZH2 inhibitor. These findings may provide evidence to support the development of GSK-126 as a clinical drug.
Stigmatization and discrimination of people with obesity due to their weight are a common problem that may lead to additional weight gain. This study evaluated the influence of different parameters on the stigmatization of obesity.
Participants of six groups (general population, patients with obesity, medical students, physicians, nurses in training and nurses; n = 490) answered the short-form fat phobia scale (FPS) between August 2016 and July 2017. The influence of body mass index (BMI), gender and other factors on total scores and single adjective pairs was analyzed.
A total of 490 participants were evaluated. The total mean FPS rating was 3.5 ± 0.6. FPS was significantly lower (more positive) in participants with obesity (3.2 ± 0.7) compared with participants without obesity (3.5 ± 0.5, p < 0.001). Individuals with obesity and diabetes rated the FPS significantly lower (more positive), whereas age and gender did not have a significant influence. Participants with obesity linked obesity more ofteng. attractive or active), whereas people without obesity linked negative characteristics with obesity. Gender had an influence only on single items of FPS but did not affect overall stigmatization of obesity.
Current gastric cancer staging systems overlook the anatomic extent of metastatic lymph nodes (AEMLNs). This study aimed to analyze the prognostic impact of AEMLNs on gastric cancer (GC).
GC patients with metastatic lymph nodes (MLNs) undergoing curative surgery were retrospectively reviewed and assigned to perigastric (MLNs in station 1-6, PG) and extraperigastric group (7-12, with or without MLNs in PG area, EPG). Overall survival (OS), disease-free survival (DFS) and recurrence patterns were compared before and after 11 propensity score matching (PSM).
662 patients were enrolled, 341 (51.5%) and 321 (48.5%) of whom were in the PG and EPG, respectively. After PSM (n = 195), EPG showed poorer 5-year OS (43.4% vs 54.5%, p = 0.014) and DFS (65.0% vs 73.4%, p = 0.068) than PG. EPG had higher incidence of peritoneal recurrence (PR) than PG (19.4% vs 7.4%, p = 0.002). Multivariate analysis identified AEMLNs as prognostic factor for OS [HR = 1.409, 95% confidence interval (CI) 1.062-1.868), DFS (HR = 1.600, 95% CI 1.059-2.416) and PR (HR = 3.708, 95% CI 1.685-8.160).
The anatomic extent of metastatic lymph nodes has an independent prognostic role for GC. Including this element may improve the accuracy of current staging systems.
The anatomic extent of metastatic lymph nodes has an independent prognostic role for GC. Including this element may improve the accuracy of current staging systems.
The coronavirus disease (COVID-19) pandemic has had a profound impact on cancer care in the US Guidelines focused on the management of COVID-19, rather than healthcare needs of breast cancer patients requiring access to crucial services. This US survey of breast cancer survivors characterizes treatment delays early period in the pandemic.
We developed a survey and administered itto 609 adult breast cancer survivors in the US. We used snowball sampling with invitations distributed via social media. We used logistic regression to select a model of delay from a pool of independent variables including race, cancer stage, site of care, health insurance, and age. We used descriptive statistics to characterize delay types.
Forty-four percent of participants reported cancer care treatment delays during the pandemic. Delays in all aspects of cancer care and treatment were reported. The only variable which had a significant effect was age (97 (.95, 99), p < 0.001) with younger respondents (M = 45.94, SD = 10.31) reporting a higher incidence of delays than older respondents (M = 48.PIN1 inhibitor API-1 manufacturer
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