Hayennis9899
The aim of this study was to examine whether or notintermittent hypoxia (IH) upregulated autophagy and the contributions of autophagy to endothelial apoptosis and dysfunction in human umbilical vein endothelial cells (HUVECs).
HUVECs were incubated under normoxia and IH conditions. After 3-, 6-, 12-, and 24-h exposure, the autophagic vacuoles and autophagosomes were observed by transmission electron microscopy and monodansylcadaverine staining. The protein levels of autophagy-related biomarkers and AMPK/mTOR pathway were measured by Western blot. The apoptosis-related proteins and the percentage of apoptotic cells were evaluated by Western blot and flow cytometry, respectively, while the levels of endothelial function biomarkers were assessed by ELISA.
IH induced autophagy, as determined by the increased numbers of the autophagic vacuoles, autophagosomes, and by the elevated levels of Beclin-1 protein, the LC3II/LC3I ratio, and p62 degradation. IH-induced autophagic flux peaked at 12-h duration and weakened at 24 h. IH increased the ratio of p-AMPK/AMPK and decreased the ratio of p-mTOR/mTOR, while compound C restored the alteration. A significant decrease in the Bcl-2 level and the Bcl-2/Bax ratio and a significant increase in the protein expression levels of Bax and cleaved caspase 3 and in the percentage of apoptosis were observed under IH exposure. Moreover, the NO level was reduced, while the ET-1 and VEGF levels were raised under IH condition. These alterations were suppressed by the pretreatment of 3-methyladenine.
IH upregulates autophagy through AMPK/mTOR pathway in HUVECs in vitro, which might be protective against endothelial apoptosis and dysfunction caused by IH.
IH upregulates autophagy through AMPK/mTOR pathway in HUVECs in vitro, which might be protective against endothelial apoptosis and dysfunction caused by IH.Prominent gaps exist between science and practice in the field of nature-based solutions (NBS) worldwide, with relatively well formulated concepts but less clear application procedures. China urgently needs to address this gap because many so called NBS practices advance rapidly nowadays, including river landscapes. Advocating planning as a bridging procedure in China's top down governance system, this study introduces NBS planning for the Jialing River in Wusheng County to address three challenges how to transform the riverfront planning from specialized to holistic, how to effectively communicate NBS in planning, and how to incorporate both scientific results and local wisdom into NBS decision-making. A planning scope was negotiated to incorporate holistic solutions. Five NBS paradigms were identified for better communication, and then spatially allocated with specific design guidelines and governance strategies. Our pilot study calls for reflection on the communication of NBS to the public, and alternative models of NBS implementations customized to different government regimes.Dementia is a devastating disease associated with aging. Alzheimer's disease is the most common form of dementia, followed by vascular dementia. In addition to clinically diagnosed dementia, cognitive dysfunction has been reported in diabetic patients. Recent studies are now beginning to recognize type 2 diabetes mellitus, characterized by chronic hyperglycemia and insulin resistance, as a risk factor for Alzheimer's disease and other cognitive disorders. While studies on insulin action have remained traditionally in the domain of peripheral tissues, the detrimental effects of insulin resistance in the central nervous system on cognitive dysfunction are increasingly being reported by recent clinical and preclinical studies. The findings from these studies suggest that antidiabetic drugs have the potential to be used to treat dementia. In this review, we discuss the physiological functions of insulin in the brain, studies on the evaluation of cognitive function under conditions of insulin resistance, and reports on the beneficial actions of antidiabetic drugs in the brain. This review covers clinical studies as well as investigations in animal models and will further highlight the emerging link between insulin resistance and neurodegenerative disorders.Aberrant DNA methylation is closely associated with the pathogenesis of Parkinson's disease (PD). DNA methyltransferases (DNMTs) are the enzymes for establishment and maintenance of DNA methylation patterns. It has not been clearly defined how DNMTs respond in PD and what mechanisms are associated. Models of PD were established by treatment of five different neurotoxins in cells and intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. Plasma samples of PD patients were also used. Western blot, real-time PCR, immunostaining, and/or luciferase reporter were employed. DNA methylation was analyzed by the bisulfite sequencing analysis. Protein expression of DNMT1, but not of DNMT3A and DNMT3B, was reduced in the cellular and mouse models of PD. Paradoxically, mRNA levels of DNMT1 were increased in these models. After ruling out the possibility of protein degradation, we screened a set of miRNAs that potentially targeted DNMT1 3'-UTR by luciferase reporters and expression abundancies. miR-17 was identified for further investigation with miR-19a of low expression as a parallel comparison. Although exogenous transfection of either miR-17 or miR-19a mimics could inhibit DNMT1 expression, results of miRNA inhibitors showed that miR-17, but not miR-19a, endogenously regulated DNMT1 and the subsequent DNA methylation. Furthermore, levels of miR-17 were elevated in the neurotoxin-induced PD models and the plasma of PD patients. This study demonstrates that the miR-17-mediated DNMT1 downregulation underlies the aberrant DNA methylation in PD. Our results provide a link bridging environmental insults and epigenetic changes and implicate miR-17 in therapeutical modulation of DNA methylation in PD.
To evaluate and compare outcomes of CO
laser-assisted sclerectomy surgery (CLASS) with mitomycin C (MMC) combined with or without phacoemulsification in adult Asian glaucoma patients.
Retrospective, comparative study.
Adult Asian glaucoma patients who underwent CLASS alone or combined with phacoemulsification using standardized surgery by two trained glaucoma surgeons between 2014 and 2016 were identified. selleck The main measures of outcome were intraocular pressure (IOP), use of supplemental medical therapy, best-corrected visual acuity (BCVA), microperforations, macroperforations, and repeated intervention(s) for glaucoma.
Forty-one eyes who underwent CLASS alone (13 eyes) or combined with phacoemulsification (28 eyes) were included. Overall, BCVA improved from 0.28 ± 0.19 to 0.14 ± 0.17, and 0.17 ± 0.19, 0.22 ± 0.24, and 0.18 ± 0.23 at 6, 12, 24, and 36months, respectively. Mean IOP dropped from 17.9 ± 4.7mmHg to 14.6 ± 5.5, 13.9 ± 3.3, 14.3 ± 3.6, and 14.1 ± 3.7mmHg, and average number of medications reduced from 2.
