11/14/2024


Expression of the RE1-silencing transcription factor (REST), a master regulator of neurogenesis, is elevated in medulloblastoma (MB) tumors. A cell-intrinsic function for REST in MB tumorigenesis is known. However, a role for REST in the regulation of MB tumor microenvironment has not been investigated. Here, we implicate REST in remodeling of the MB vasculature and describe underlying mechanisms. Using RESTTG mice, we demonstrate that elevated REST expression in cerebellar granule cell progenitors, the cells of origin of sonic hedgehog (SHH) MBs, increased vascular growth. This was recapitulated in MB xenograft models and validated by transcriptomic analyses of human MB samples. REST upregulation was associated with enhanced secretion of proangiogenic factors. Surprisingly, a REST-dependent increase in the expression of the proangiogenic transcription factor E26 oncogene homolog 1, and its target gene encoding the vascular endothelial growth factor receptor-1, was observed in MB cells, which coincided with their localization at the tumor vasculature. These observations were confirmed by RNA-Seq and microarray analyses of MB cells and SHH-MB tumors. Thus, our data suggest that REST elevation promotes vascular growth by autocrine and paracrine mechanisms.
We prospectively examined the relationship between metabolic syndrome (MetS) and incident chronic kidney disease (CKD) among middle-aged and elderly Chinese, and conducted a systematic review and meta-analysis of all cohort studies on this topic.

Our research data were derived from the China Health and Retirement Longitudinal Study. Participants (n=5752, age ≥45 years) without CKD (defined as estimated glomerular filtration rate <60ml/min/1.73m
) at baseline were followed up for 4 years. We applied logistic regressions to examine the association of MetS with incident CKD. In addition, we pooled our effect estimates and those from previous cohort studies in the meta-analysis.

In a 4-years follow-up, 61 (4.27%) developed CKD in participants with MetS versus 102 (2.36%) in participants without MetS. After adjustment for potential confounders, odds ratio for incident CKD was 1.82 [95% confidence interval (95% CI) 1.19-2.78] comparing participants with MetS with those without MetS. There was a linear positive association between the number of MetS components and incident CKD (p for trend <0.001). https://www.selleckchem.com/products/thal-sns-032.html In the updated meta-analysis of 25 studies among 350,655 participants with 29,368 incident cases of CKD, the pooled relative risk of developing CKD in participants with MetS was 1.34 (95% CI 1.28-1.39), compared with those without MetS.

Individuals with MetS had higher risk of incident CKD in middle-aged and elderly Chinese adults, which was supported by a comprehensive review of cohort studies from multiple populations. It may be advisable to routinely monitor renal functions among individuals with MetS.
Individuals with MetS had higher risk of incident CKD in middle-aged and elderly Chinese adults, which was supported by a comprehensive review of cohort studies from multiple populations. It may be advisable to routinely monitor renal functions among individuals with MetS.Chronic stress (CS) is shown to decrease the semen quality with changed expression of tyrosine phosphorylated (TyrPho) proteins in testicular and seminal tissues. However, the alterations of such proteins and fluid contents in the epididymis, producing sperm maturation factors, have never been reported. Sixteen adult rats were randomly divided into 2 groups (n = 8). The control animals were not subjected to stressors whereas CS rats were immobilised within restraint cage (4 hr/day) before cold forced-water swimming (15 min/day) for 60 days. Corticosterone, testosterone, blood glucose level (BGL), malondialdehyde (MDA) and biochemical components in epididymal fluid were assayed. Expressions of heat shock protein 70 (HSP-70), androgen receptor (AR) and TyrPho protein were investigated in epididymal tissue and fluid. Significantly, CS increased the corticosterone and BGL but decreased testosterone and epididymal substance levels. MDA level in tail epididymal fluid and HSP-70 expression in both regions of epididymal tissues and fluids, except in head epididymal fluid of CS were increased. Epididymal tissues showed the decrease of AR expression. Presence and changes of many TyrPho proteins were observed in CS. In conclusion, CS could affect functional proteins particularly TyrPho in epididymis, resulted in low semen quality.Intraneuronal accumulation of hyperphosphorylated tau is a pathological hallmark of several neurodegenerative disorders, including Alzheimer's disease. Phosphorylation plays a crucial role in modulating the tau-microtubule interaction and the ability of the protein to aggregate, but despite efforts during the past decades, the real identity of the kynases involved in vivo remains uncertain. Here, for the first time, we demonstrate that the cGMP-dependent protein kinase G (PKG) phosphorylates tau in both in vitro and in vivo models. More intriguingly, we provide evidence that PKG phosphorylates tau at Ser214 but not at Ser202, a condition that could reduce the pathological aggregation of the protein shifting tau from a pro-aggregant to a neuroprotective anti-aggregant conformation.
The objective of this study was to systematically compare the transfer accuracy of conventional and digital implant impressions in patients using a new reference key-based method.

Thirty-nine cases were included in the study (upper jaw 22 edentulous, 8 partially edentulous, average distance between implants 30.15±11.18mm; lower jaw 6 cases edentulous, 3 cases partially edentulous, average distance between implants 33.19±14.85mm). Individual reference keys were manufactured and reversibly fixed on implants. A conventional (CVI) and a digital (DI) implant impression was made. The implant positions (center points) of conventional and digital models were measured (coordinate-measuring machine/three-dimensional analysis software) and superimposed with the positions of the reference keys to compare the deviations of the conventional and digital models. For statistical analysis, ANOVA with MIXED procedure was applied (p<.05).

Mean deviation ranged from 0.040±0.029mm (DI/upper jaw) to 0.079±0.050mm (DI/lower jaw).