Biology subjects

Hampel, H.

Publications and source records attributed to Hampel, H..

3 recordsLinked to original sources

bioRxiv2026

Peptidylglycine α-amidating monooxygenase restores brain microvascular blood flow and improves recovery following ischemic stroke

IntroductionReduced or absent capillary blood flow (termed no-reflow) even after arterial recanalization is associated with poorer neurological outcomes following ischemic stroke. The aim of the current study was to test whether acute administration of peptidylglycine -amidating monooxygenase (PAM) can increase capillary blood flow and improve brain recovery after ischemic stroke. MethodsA 60-minute ischemic stroke was induced using middle cerebral artery occlusion (MCAO) in rats. A modified, long-acting PAM enzyme was administered 30 minutes after induction of ischemia and rats were recovered for either 24 hours or 7 days. In all animals, real-time cerebral blood flow was assessed before, during and after MCAO using trasncranial contrast enhanced ultrasound (tCEU). For rats in the 7-day protocol, a modified neuroscore test was used to assess neurological deficit following MCAO. At the end of each experiment, a transcardiac perfusion was used to generate a fluorescent vascular cast and histology was used to examine capillary diameters and determine infarct volume. ResultsFollowing MCAO and arterial recanalization, untreated rats had reduced cerebral blood flow across brain regions affected by ischemia, indicative of no-reflow. PAM administration led to enhanced cerebral blood flow in affected regions, and this was associated with increased capillary diameters 24 hours after ischemic stroke. Although there was no difference in infarct volume at 24 hours, by day 7, infarct volume was markedly reduced in the PAM group and these animals exhibited improved neurological function compared to the untreated group. ConclusionAdministration of PAM improves capillary blood flow after ischemic stroke leading to enhanced neurological and brain recovery. This work highlights PAM as a novel theraputic approach to improve brain blood flow and recovery after ischemic stroke. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/732201v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@3095ddorg.highwire.dtl.DTLVardef@1bf159borg.highwire.dtl.DTLVardef@239afdorg.highwire.dtl.DTLVardef@19476e3_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2026

Global Proteomic Analysis of Colorectal Cancers Stratified by Microsatellite Instability Subtype Reveals Protein Differences

Lynch syndrome, historically known as hereditary nonpolyposis colorectal cancer, is caused by germline mutations in the DNA mismatch repair (MMR) genes, MLH1, MSH2 (EPCAM), MSH6, and PMS2. While the genetic changes associated with Lynch Syndrome have previously been characterized, there have not been studies of the associated proteomic alterations, in part because of the limited availability of primary samples and the absence of in vitro model systems. In this study, the first large-scale tissue proteomic assessment of Lynch Syndrome samples as well as three other subtypes of colorectal cancer was completed with specimens from the Ohio Colorectal Cancer Prevention Initiative. The cohort contained three groups of microsatellite unstable (MSI-high) CRC patients (Lynch syndrome, double somatic MMR mutation, and MLH1 hypermethylation) and a group of microsatellite stable (MSS) CRC patients. A total of 122 tumor and complimentary normal mucosa samples from 61 patients were evaluated using label-free bottom-up proteomic analysis. Hierarchical clustering analysis of the global proteome showed that the MSS group was significantly different than the three MSI-high groups. Of the 1,084 proteins found to be dysregulated across all four colorectal cancer subtypes, there were age at diagnosis associated shifts in proteins correlated with tumor proliferation and immune regulation for the Lynch syndrome and Double Somatic samples. The proteins TPD52, GMDS, and DSP showed increased protein abundance correlated with older age at diagnosis. In addition, the Lynch syndrome samples showed substantial sex-based differences in immune and inflammatory pathways, for example, downregulation of ZG16, DIS3, and WDR43. This study fills a critical gap as the first proteomic characterization of Lynch syndrome samples to date. Data are available via ProteomeXchange with identifier PXD073693. TeaserThis is the first study of the global proteomic differences between Lynch Syndrome and other forms of colorectal cancer.

cancer biology↗

bioRxiv2019

Physical activity and risks of breast and colorectal cancer: A Mendelian randomization analysis

Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomization analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.42 to 0.84, P-value=0.003) and colorectal cancer (OR: 0.66, 95% CI: 0.53 to 0.82, P-value=2*E-4). We found similar magnitude inverse associations by breast cancer subtype and by colorectal cancer anatomical site. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers.\n\nDisclaimerWhere authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization.

genetics↗