Loxenatide attenuates ROS-mediated vascular endothelial progenitor cell damage and mitochondrial dysfunction via SIRT3/Foxo3 signaling pathway.

Diabetes mellitus (DM), becomes a main public health issue worldwide due to the rapid increase in DM patient numbers. The dysfunction of endothelial progenitor cells (EPCs) in DM patients plays a critical role in endothelial repair and the progression of DM-related vascular complications. Loxenatide is an a glucagon-like peptide 1 receptor agonist, which is used to control glycemic in type 2 diabetes patients. However, the role of Loxenatide in EPCs remains to be investigated. EPCs were isolated, characterized, and treated with Loxenatide, high-glucose, or 3-TYP. quantitative real-time polymerase chain reaction, flow cytometry, western blot, and cell counting kit-8 assay were employed to validate the expression of gene and protein expressions and cell viability, respectively. Application of Seahorse XFp to measure oxygen consumption and mitochondrial membrane potential (MMP) were measured by Seahorse XFp and MMP assay. Loxenatide attenuated high-glucose-induced reactive oxygen species (ROS) production and mitochondrial-dependent apoptosis of EPCs in a concentration-dependent manner. The EPC mitochondrial respiration dysfunction induced by high glucose was also repressed by the loxenatide treatment. The protection effect of Loxenatide on EPCs against high-glucose was applied by activating the sirtuin 3 (SIRT3)/Foxo3 signaling pathway. We demonstrated the regulatory role of Loxenatide in mitochondrial dysfunction and apoptosis of EPCs. We elucidated that Loxenatide protects EPC from high-glucose-induced apoptosis via ROS-mediated mitochondrial pathway through the SIRT3/Foxo3 signing pathway. This may provide a new therapeutical target for the treatment of DM-related vascular complications.

METTL3-stabilized lncRNA SNHG7 accelerates glycolysis in prostate cancer via SRSF1/c-Myc axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as novel players in cancer metabolism. lncRNA small nucleolar RNA host gene 7 (SNHG7) plays an oncogenic role in prostate cancer (PCa). However, the role and mechanism of SNHG7 in PCa metabolism remain largely undefined. METHODS: A cohort of 30 PCa tumors and their counterparts were collected. qRT-PCR was employed to detect target gene expression and RNA stability. CCK-8 assay was used to assess cell viability. N6-methyladenosine (m6A) level was measured by a commercial kit. Cell glycolysis was evaluated by measuring glucose uptake, lactate, ATP production and Extracellular acidification rate (ECAR). Bioinformatics analysis and RNA immunoprecipitation (RIP) assay were used to verify the interactions among SNHG7, serine/arginine-rich splicing factor 1 (SRSF1) and c-Myc. RESULTS: SNHG7 and c-Myc were highly expressed in PCa tissues and cells. Methyltransferase-like 3 (METTL3)-mediated m6A modification of SNHG7 and enhanced its stability. Silencing of SNHG7 suppressed proliferation and glycolysis in PCa cells. Mechanistically, SNHG7 regulated c-Myc via interacting with SRSF1. Gain- and loss-of function experiments revealed that SNHG7 promoted glycolysis via SRSF1/c-Myc axis in PC-3 and DU-145 cells. CONCLUSION: METTL3-stabilized lncRNA SNHG7 accelerates glycolysis in PCa via SRSF1/c-Myc axis and inspires the understanding of m6A roles in lncRNA metabolism and tumor progression.

Effects of Climate Change on Land Cover Change and Vegetation Dynamics in Xinjiang, China.

Since the Silk-road Economic belt initiatives were proposed, Xinjiang has provided a vital strategic link between China and Central Asia and even Eurasia. However, owing to the weak and vulnerable ecosystem in this arid region, even a slight climate change would probably disrupt vegetation dynamics and land cover change. Thus, there is an urgent need to determine the Normalized Difference Vegetation Index (NDVI) and Land-use/Land-cover (LULC) responses to climate change. Here, the extreme-point symmetric mode decomposition (ESMD) method and linear regression method (LRM) were applied to recognize the variation trends of the NDVI, temperature, and precipitation between the growing season and other seasons. Combining the transfer matrix of LULC, the Pearson correlation analysis was utilized to reveal the response of NDVI to climate change and climate extremes. The results showed that: (1) Extreme temperature showed greater variation than extreme precipitation. Both the ESMD and the LRM exhibited an increased volatility trend for the NDVI, with the significant improvement regions mainly located in the margin of basins. (2) Since climate change had a warming trend, the permanent snow has been reduced by 20,436 km2. The NDVI has a higher correlation to precipitation than temperature. Furthermore, the humid trend could provide more suitable conditions for vegetation growth, but the warm trend might prevent vegetation growth. Spatially, the response of the NDVI in North Xinjiang (NXC) was more sensitive to precipitation than that in South Xinjiang (SXC). Seasonally, the NDVI has a greater correlation to precipitation in spring and summer, but the opposite occurs in autumn. (3) The response of the NDVI to extreme precipitation was stronger than the response to extreme temperature. The reduction in diurnal temperature variation was beneficial to vegetation growth. Therefore, continuous concentrated precipitation and higher night-time-temperatures could enhance vegetation growth in Xinjiang. This study could enrich the understanding of the response of land cover change and vegetation dynamics to climate extremes and provide scientific support for eco-environment sustainable management in the arid regions.