Low energy within Renal system Transplantation: An organized Evaluate as well as Meta-Analysis.
 Small extracellular vesicles (sEVs) as natural membranous vesicles are on the frontiers of nanomedical research, due to their ability to deliver therapeutic molecules such as microRNAs (miRNAs). The miRNA-21 (miR-21) is thought to be involved in the initiation and development of myocardial infarction (MI). Here, we examined whether miR-21 regulation using human peripheral blood-derived sEVs (PB-sEVs) could serve as a potential therapeutic strategy for MI. First, we examined miR-21 levels in hypoxic conditions and validated the ability of PB-sEVs to serve as a potential delivery system for miRNAs. Further, bioinformatics analysis and luciferase assay were performed to identify target genes of miR-21 mechanistically. Among numerous target pathways, we focused on nitrogen metabolism, which remains relatively unexplored compared with other possible miR-21-mediated pathways; hence, we aimed to determine novel target genes of miR-21 related to nitrogen metabolism. In hypoxic conditions, the expression of miR-21 was significantly up-regulated and correlated with nitric oxide synthase 3 (NOS3) levels, which in turn influences cardiac function. The down-regulation of miR-21 expression by PB-sEVs loaded with anti-miR-21 significantly improved survival rates, consistent with the augmentation of cardiac function. However, the up-regulation of miR-21 expression by PB-sEVs loaded with miR-21 reversed these effects.  https://www.selleckchem.com/products/Rapamycin.html  Mechanistically, miR-21 targeted and down-regulated the mRNA and protein expression of striatin (STRN), which could regulate NOS3 expression. In conclusion, we identified a novel therapeutic strategy to improve cardiac function by regulating the expression of miR-21 with PB-sEVs as an miR-21 or anti-miR-21 delivery vehicle and confirmed the miR-21-associated nitrogen metabolic disorders in MI.  https://www.selleckchem.com/products/Rapamycin.html  © 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.Lateral medullary arteriovenous malformations (AVMs) are located in the pia on the lateral medullary surface.1 They are supplied by arterial feeders from the V4 segment of the vertebral artery or posterior inferior cerebellar artery. A 64-yr-old man presented with leg spasms and progressively worsening gait. Angiography demonstrated a lateral medullary AVM. Patient consent was obtained for the surgical treatment of this lesion. Owing to its eloquent location, an occlusion in situ was performed without resection.1,2 This technique relies on the interruption of the arterial blood supply and occlusion of the draining vein to occlude the AVM. Intraoperative neurophysiological monitoring of motor and somatosensory evoked potentials was used, and the elimination of arteriovenous shunt flow was confirmed using indocyanine green videoangiography. Occlusion in situ preserves the flow to the delicate brainstem perforators and is safer than resection in selected cases like this one. Used with permission from Barrow Neurological Institute, Phoenix, Arizona. Copyright © 2020 by the Congress of Neurological Surgeons.Thymineguanine base pairs are major promutagenic mismatches occurring in DNA metabolism. If left unrepaired, these mispairs can cause C to T transition mutations. In humans, TG mismatches are repaired in part by mismatch-specific DNA glycosylases such as methyl-CpG-binding domain 4 (hMBD4) and thymine DNA glycosylase. Unlike lesion-specific DNA glycosylases, TG-mismatch-specific DNA glycosylases specifically recognize both bases of the mismatch and remove the thymine but only from mispairs with guanine. Despite the advances in biochemical and structural characterizations of hMBD4, the catalytic mechanism of hMBD4 remains elusive. Herein, we report two structures of hMBD4 processing TG-mismatched DNA. A high-resolution crystal structure of Asp560Asn hMBD4-TG complex suggests that hMBD4-mediated glycosidic bond cleavage occurs via a general base catalysis mechanism assisted by Asp560. A structure of wild-type hMBD4 encountering TG-containing DNA shows the generation of an apurinic/apyrimidinic (AP) site bearing the C1´-(S)-OH. The inversion of the stereochemistry at the C1´ of the AP-site indicates that a nucleophilic water molecule approaches from the back of the thymine substrate, suggesting a bimolecular displacement mechanism (SN2) for hMBD4-catalyzed thymine excision. The AP-site is stabilized by an extensive hydrogen bond network in the MBD4 catalytic site, highlighting the role of MBD4 in protecting the genotoxic AP-site. Copyright 2020 The Author(s).CONTEXT/OBJECTIVE Increases of thyroid cancer (TC) incidence emerged in the last decades in several countries. This study aimed to estimate time trends of TC incidence in India and the proportion of TC cases potentially attributable to overdiagnosis by sex, age, and area. DESIGN TC cases aged 0-74 years reported to Indian cancer registries during 2006-2014 were included. Age-standardized incidence rates (ASR) and TC overdiagnosis were estimated by sex, period, age, and area. RESULTS Between 2006-2008 and 2012-2014, the ASRs for TC in India increased from 2.5 to 3.5/100,000 women (+37%) and from 1.0 to 1.3/100.000 men (+27%). However, up to a 10-fold difference was found among regions in both sexes. Highest ASRs emerged in Thiruvananthapuram (14.6/100,000 women and 4.1/100,000 men in 2012-2014), with 93% increase in women and 64% in men compared to 2006-2008. No evidence of overdiagnosis was found in Indian men. Conversely, overdiagnosis accounted for 51% of TC in Indian women 74% in those aged less then 35 years, 50% at ages 35-54 years, and 30% at ages 55-64 years. In particular, 80% of TC overdiagnosis in women emerged in Thiruvananthapuram, while none or limited evidence of overdiagnosis emerged in Kamrup, Dibrugarh, Bhopal, and Sikkim. CONCLUSIONS Relatively high and increasing TC ASRs emerged in Indian regions where better access to healthcare was reported. In India, as elsewhere, new strategies are needed to discourage opportunistic screening practice, particularly in young women, and to avoid unnecessary and expensive treatments. Present results may serve as a warning also for other transitioning countries. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.