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Immortalized mouse hepatocytes (AML12 cells) were used to validate the gene changes induced by TGF-β stimulation and CAV1 knockdown. Noteworthy, of the TGF-β metabolic target genes, CAV1 modulated the expression of 228 (27%). In conclusion, we present several novel metabolic gene signatures of TGF-β in hepatocytes and show that CAV1 abundance alters almost a third of these genes. These findings could enable a better understanding of TGF-β function in normal and diseased liver especially where differential CAV1 level is implicated. Copyright © 2020 Han, Nwosu, Piorońska, Ebert, Dooley and Meyer.Introduction Diving close to the Arctic circle means diving in cold water regardless of the time of year. The human body reacts to cold through autonomous nervous system (ANS)-mediated thermoregulatory mechanisms. Diving also induces ANS responses as a result of the diving reflex. https://www.selleckchem.com/products/FK-506-(Tacrolimus).html Materials and Methods In order to study ANS responses during diving in Arctic water temperatures, we retrospectively analyzed repeated 5-min heart rate variability (HRV) measures and the mean body temperature from dives at regular intervals using naval diving equipment measurement tests in 0°C water. Three divers performed seven dives without physical activity (81-91 min), and two divers performed four dives with physical activity after 10 min of diving (0-10 min HRV recordings were included in the study). Results Our study showed a significant increase in parasympathetic activity (PNS) at the beginning of the dives, after which PNS activity decreased significantly (measure 5-10 min). Subsequent measurements (15-20 min and onward) showed a significant increase in PNS activity over time. Conclusion Our results suggest that the first PNS responses of the human diving reflex decrease quickly. Adverse effects of PNS activity should be considered on long and cold dives. To avoid concurrent sympathetic (SNS) and PNS activity at the beginning of dives, which in turn may increase the risk of arrhythmia in cold water, we suggest a short adaptation phase before physical activity. Moreover, we suggest it is prudent to give special attention to cardiovascular risk factors during pre-dive examinations for cold water divers. Copyright © 2020 Lundell, Räisänen-Sokolowski, Wuorimaa, Ojanen and Parkkola.Background There are great individual differences in the drug responses; however, there are few prognostic drug response biomarkers available. RELN is one of the more extensively examined schizophrenia candidate genes. The purpose of this study was to determine whether RELN can affect antipsychotics response in the Chinese population. This may lead to the discovery of relevant novel drug response markers. Methods The unrelated 260 Chinese Han inpatients with schizophrenia were enrolled in the present study. The enrolled subjects have been prescribed antipsychotic medication during the study. A total of 15 SNPs of RELN were genotyped by MassARRAY® platform. The association of the RELN gene with therapeutic response to antipsychotics was analyzed based on sex and age at onset. Results Two novel SNPs of RELN were found to be associated with antipsychotic treatment response (rs155333, p = 0.010 and rs6465938, p = 0.049) at nominal significance threshold, but not after multiple correction. Our study also revealed highly significant association of a haplotype consisting of three SNPs (rs362814-rs362626-rs2237628) with antipsychotic treatment response. Even after permutation, the p-value indicated significant association (rs362814-rs362626-rs2237628 ACT, χ2 = 6.353, p = 0.0117, permuted p = 0.04). Furthermore, a novel SNP, rs2535764, was found to be associated with antipsychotic response under overdominant genetic model at a marginal significant level of 0.046 (C/T vs. C/C + T/T p = 0.046, AIC = 314.7, BIC = 321.6). Conclusion Our data indicated that RELN can affect antipsychotic treatment outcomes in the Chinese population. SNPs of RELN could be used as predictive biomarkers for future personalized medicine of antipsychotic drug treatment. However, none of the three novel SNPs (rs155333, rs6465938, and rs2535764) remained significant after Bonferroni correction. Therefore, validation is needed in larger pharmacogenetic studies. Copyright © 2020 Xu, Li, Qin, Li, Ning, Fu, Wang, Zeng, Li, Yu and Yu.Purpose Diabetic retinopathy (DR), a neurovascular disease, is one of the leading causes of blindness in working-age adults. Long noncoding RNAs (lncRNAs) have attracted attention as indicators for DR. This study aimed to characterize the role of lncRNA human testis development-related gene 1 (TDRG1) and its modulation of vascular endothelial growth factor (VEGF) in deteriorating DR. Methods Tissue samples were obtained from patients with epiretinal membranes (EMs) or proliferative DR, and human retinal microvascular endothelial cells (HRECs) were cultured with high-glucose medium to mimic DR as the in vitro model. The expression of lncRNA TDRG1 and VEGF was determined by immunofluorescence staining, Western blotting, and RT-qPCR. Transfection of small-interfering RNA was conducted to knock down target gene expression. HREC functions were evaluated by cell viability, fluorescein isothiocyanate (FITC)-dextran extravasation, migration, and tube formation assays under different conditions. Results LncRNA TDRG1 and VEGF were found to be co-expressed and significantly upregulated in fibrovascular membranes (FVMs) from DR patients compared to those from EM patients. In the in vitro model, hyperglycemic treatment markedly increased the expression of lncRNA TDRG1 and VEGF at the mRNA and protein levels, which promoted cell proliferation and migration, enhanced permeability, and disrupted tube formation of HRECs. However, knockdown of lncRNA TDRG1 or VEGF notably decreased the expression of VEGF and reversed the impaired functions of high-glucose-treated HRECs. Conclusions LncRNA TDRG1 promoted microvascular cell dysfunction via upregulating VEGF in the progression of DR and may serve as a potential therapeutic target in DR treatment. Copyright © 2020 Gong, Dong, Fan, Chen, Bian, Xu, Qian and Yu.
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