GENOME-SCALE METHYLATION ANALYSIS IN BLOOD AND TUMOR IDENTIFIES IMMUNE PROFILE, AGE ACCELERATION, AND DNA METHYLATION ALTERATIONS ASSOCIATED WITH BLADDER CANCER OUTCOMES

Bladder cancer patients receive frequent screening due to the high tumor recurrence rate (more than 60%). Nowadays, the conventional monitoring method relies on cystoscopy which is highly invasive and increases patient morbidity and burden to the health care system with frequent follow-up. As a result, it is urgent to explore novel markers related to the outcomes of bladder cancer. Immune profiles have been associated with cancer outcomes and may have the potential to be biomarkers for outcomes management. However, little work has been conducted to investigate the associations of immune cell profiles with bladder cancer outcomes. Here, I utilized the Illumina HumanMethylationEPIC array to measure DNA methylation profiles of peripheral blood and matched tumor tissues of bladder cancer cases recruited in a population-based cohort study in New Hampshire. Then, cell-type deconvolution was applied to quantify immune cell-type proportions, and three epigenetic clocks were estimated for calculating age acceleration. Cox proportional hazard models were performed to test the association of methylation-derived profiles with bladder cancer outcomes. The partDSA algorithm and a semi-supervised recursively partitioned mixture model were conducted to determine overall survival groups based on immune cell profiles, clinical variables, and DNA methylation level. We used an epigenome‐wide association study approach adjusting for immune cell profiles to identify CpG sites associated with the hazard of bladder cancer outcomes, and then, those identified CpG sites were used for enrichment analyses. Finally, we evaluated the association between circulating immune cell-type proportions with the cell-type proportions in the tumor microenvironment. We demonstrated that highly circulating CD4T memory and CD8T memory cell proportions were significantly associated with a decreased hazard of tumor recurrence or death, whereas high neutrophil cell proportion, NLR, and age acceleration were associated with an increased hazard of tumor recurrence or death. Collectively, we identified associations of methylation-derived immune profiles and age acceleration with bladder cancer outcomes that may facilitate the development of bladder cancer prognostic biomarkers

The role of microRNAs in the pathogenesis of autoimmune diseases

K

Neuroprotection of Catalpol for Experimental Acute Focal Ischemic Stroke: Preclinical Evidence and Possible Mechanisms of Antioxidation, Anti-Inflammation, and Antiapoptosis

Neuroprotection is defined as using a therapy that affects the brain tissue in the still-viable ischemic penumbra to salvage or delay the infarction. Catalpol, the main active principle of the root of Radix Rehmanniae, was reported to have pleiotropic neuroprotective effects in neurodegenerative diseases including ischemic stroke. Here, we evaluated the neuroprotective effects of catalpol in experimental acute ischemic stroke. Studies on catalpol in animal models of acute ischemic stroke were identified from 6 databases. Twenty-five studies involving 805 animals were included. Twelve comparisons showed significant effects of catalpol on decreasing infarct size according to 2,3,5-triphenyltetrazolium chloride staining compared with the control (P<0.05). One study reported significant effect of catalpol on reducing infarct size according to magnetic resonance imaging scan compared with the control (P<0.05). Meta-analysis of these studies indicated that catalpol significantly improved the neurological function score according to Zea Longa score, Bederson score, balance beam-walking test, adhesive removal test, bar-grasping score, and corner test compared with the control (P<0.05). In conclusion, catalpol exerted neuroprotective effects for experimental acute focal ischemic stroke, largely through reducing oxidative reactions, inhibiting apoptosis, and repressing inflammatory reactions and autophagy. However, these apparently positive findings should be interpreted with caution because of the methodological flaws

A regioselectivity switch in Pd-catalyzed hydroallylation of alkynes.

By exploiting the reactivity of a vinyl-Pd species, we control the regioselectivity in hydroallylation of alkynes under Pd-hydride catalysis. A monophosphine ligand and carboxylic acid combination promotes 1,5-dienes through a pathway involving isomerization of alkynes to allenes. In contrast, a bisphosphine ligand and copper cocatalyst favor 1,4-dienes via a mechanism that involves transmetalation. Our study highlights how to access different isomers by diverting a common organometallic intermediate

Tetra­aqua­bis[2-(2,4-dichloro­phen­oxy)acetato]nickel(II)

In the title complex, [Ni(C8H5Cl2O3)2(H2O)4], the NiII atom (site symmetry ) adopts a slightly distorted NiO6 octa­hedral coordination. An intra­molecular O—H⋯O hydrogen bond helps to establish the conformation. In the crystal, further O—H⋯O hydrogen bonds link the mol­ecules