keyword
https://read.qxmd.com/read/38505524/inhibition-of-rankl-improves-the-skeletal-phenotype-of-adenine-induced-chronic-kidney-disease-in-mice
#21
JOURNAL ARTICLE
Corinne E Metzger, Mizuho Kittaka, Alec N LaPlant, Yasuyoshi Ueki, Matthew R Allen
Skeletal fragility and high fracture rates are common in CKD. A key component of bone loss in CKD with secondary hyperparathyroidism is high bone turnover and cortical bone deterioration through both cortical porosity and cortical thinning. We hypothesized that RANKL drives high bone resorption within cortical bone leading to the development of cortical porosity in CKD (study 1) and that systemic inhibition of RANKL would mitigate the skeletal phenotype of CKD (study 2). In study 1, we assessed the skeletal properties of male and female Dmp1-cre RANKLfl/fl (cKO) and control genotype ( Ranklfl/fl ; Con) mice after 10 wk of adenine-induced CKD (AD; 0...
February 2024: JBMR Plus
https://read.qxmd.com/read/38504097/genetic-imputation-of-kidney-transcriptome-proteome-and-multi-omics-illuminates-new-blood-pressure-and-hypertension-targets
#22
JOURNAL ARTICLE
Xiaoguang Xu, Chachrit Khunsriraksakul, James M Eales, Sebastien Rubin, David Scannali, Sushant Saluja, David Talavera, Havell Markus, Lida Wang, Maciej Drzal, Akhlaq Maan, Abigail C Lay, Priscilla R Prestes, Jeniece Regan, Avantika R Diwadkar, Matthew Denniff, Grzegorz Rempega, Jakub Ryszawy, Robert Król, John P Dormer, Monika Szulinska, Marta Walczak, Andrzej Antczak, Pamela R Matías-García, Melanie Waldenberger, Adrian S Woolf, Bernard Keavney, Ewa Zukowska-Szczechowska, Wojciech Wystrychowski, Joanna Zywiec, Pawel Bogdanski, A H Jan Danser, Nilesh J Samani, Tomasz J Guzik, Andrew P Morris, Dajiang J Liu, Fadi J Charchar, Maciej Tomaszewski
Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively)...
March 19, 2024: Nature Communications
https://read.qxmd.com/read/38503701/-development-of-an-analytical-system-for-dried-blood-spots-for-forensic-toxicology-a-case-study-of-five-common-drugs-and-poisons
#23
JOURNAL ARTICLE
Dong-Bin Su, Lin-Pei Dong, Yun-Feng Zhang, Peng Zhao, Kai-Kai Li
Dried blood spot (DBS) technology is a simple and convenient method for collecting, transporting, and storing blood samples on filter paper, and has numerous applications in the clinical, research, and public health settings. This technique is gaining popularity in the field of forensic science because it facilitates the rapid analysis of prohibited drugs in blood samples and offers significant advantages in toxicology scenarios such as drinking-driving screening, drug abuse detection, and doping detection...
March 8, 2024: Se Pu, Chinese Journal of Chromatography
https://read.qxmd.com/read/38503267/cigarette-smoking-and-e-cigarette-use-induce-shared-dna-methylation-changes-linked-to-carcinogenesis
#24
JOURNAL ARTICLE
Chiara Herzog, Allison Jones, Iona Evans, Janhavi R Raut, Michal Zikan, David Cibula, Andrew Wong, Hermann Brenner, Rebecca C Richmond, Martin Widschwendter
Tobacco use is a major modifiable risk factor for adverse health outcomes, including cancer, and elicits profound epigenetic changes thought to be associated with long-term cancer risk. While electronic cigarettes (e-cigarettes) have been advocated as harm reduction alternatives to tobacco products, recent studies have revealed potential detrimental effects, highlighting the urgent need for further research into the molecular and health impacts of e-cigarettes. Here, we applied computational deconvolution methods to dissect the cell- and tissue-specific epigenetic effects of tobacco or e-cigarette use on DNA methylation (DNAme) in over 3,500 buccal/saliva, cervical, or blood samples, spanning epithelial and immune cells at directly and indirectly exposed sites...
March 19, 2024: Cancer Research
https://read.qxmd.com/read/38503093/a-retinal-vessel-segmentation-network-with-multiple-dimension-attention-and-adaptive-feature-fusion
#25
JOURNAL ARTICLE
Jianyong Li, Ge Gao, Lei Yang, Yanhong Liu
The incidence of blinding eye diseases is highly correlated with changes in retinal morphology, and is clinically detected by segmenting retinal structures in fundus images. However, some existing methods have limitations in accurately segmenting thin vessels. In recent years, deep learning has made a splash in the medical image segmentation, but the lack of edge information representation due to repetitive convolution and pooling, limits the final segmentation accuracy. To this end, this paper proposes a pixel-level retinal vessel segmentation network with multiple-dimension attention and adaptive feature fusion...
April 2024: Computers in Biology and Medicine
https://read.qxmd.com/read/38502703/mimicking-angiogenic-microenvironment-of-alveolar-soft-part-sarcoma-in-a-microfluidic-coculture-vasculature-chip
#26
JOURNAL ARTICLE
Surachada Chuaychob, Ruyin Lyu, Miwa Tanaka, Ayumi Haginiwa, Atsuya Kitada, Takuro Nakamura, Ryuji Yokokawa
Alveolar soft-part sarcoma (ASPS) is a slow-growing soft tissue sarcoma with high mortality rates that affects adolescents and young adults. ASPS resists conventional chemotherapy; thus, decades of research have elucidated pathogenic mechanisms driving the disease, particularly its angiogenic capacities. Integrated blood vessels that are rich in pericytes (PCs) and metastatic potential are distinctive of ASPS. To mimic ASPS angiogenic microenvironment, a microfluidic coculture vasculature chip has been developed as a three-dimensional (3D) spheroid composed of mouse ASPS, a layer of PCs, and endothelial cells (ECs)...
March 26, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/38500753/computed-tomographic-angiography-measures-of-coronary-plaque-in-clinical-trials-opportunities-and-considerations-to-accelerate-drug-translation
#27
REVIEW
N Howden, K Branch, P Douglas, M Gray, M Budoff, M Dewey, D E Newby, S J Nicholls, R Blankstein, S Fathieh, S M Grieve, G A Figtree
Atherosclerotic coronary artery disease (CAD) is the causal pathological process driving most major adverse cardiovascular events (MACE) worldwide. The complex development of atherosclerosis manifests as intimal plaque which occurs in the presence or absence of traditional risk factors. There are numerous effective medications for modifying CAD but new pharmacologic therapies require increasingly large and expensive cardiovascular outcome trials to assess their potential impact on MACE and to obtain regulatory approval...
2024: Frontiers in Cardiovascular Medicine
https://read.qxmd.com/read/38500154/effectiveness-and-safety-of-the-combination-of-sodium-glucose-transport-protein-2-inhibitors-and-glucagon-like-peptide-1-receptor-agonists-in-patients-with-type-2-diabetes-mellitus-a-systematic-review-and-meta-analysis-of-observational-studies
#28
JOURNAL ARTICLE
Aftab Ahmad, Hani Sabbour
BACKGROUND: Randomized controlled trials and real-world studies suggest that combination therapy with sodium-glucose transport protein 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is associated with improvement in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), systolic blood pressure (SBP), body mass index (BMI), and total cholesterol levels. However, a systematic review of available real-world evidence may facilitate clinical decision-making in the real-world scenario...
March 18, 2024: Cardiovascular Diabetology
https://read.qxmd.com/read/38499689/metabolic-regulation-of-skeletal-cell-fate-and-function
#29
REVIEW
Steve Stegen, Geert Carmeliet
Bone development and bone remodelling during adult life are highly anabolic processes requiring an adequate supply of oxygen and nutrients. Bone-forming osteoblasts and bone-resorbing osteoclasts interact closely to preserve bone mass and architecture and are often located close to blood vessels. Chondrocytes within the developing growth plate ensure that bone lengthening occurs before puberty, but these cells function in an avascular environment. With ageing, numerous bone marrow adipocytes appear, often with negative effects on bone properties...
March 18, 2024: Nature Reviews. Endocrinology
https://read.qxmd.com/read/38498036/a-lineage-specific-stat5bn642h-mouse-model-to-study-nk-cell-leukemia
#30
JOURNAL ARTICLE
Klara Klein, Sebastian Kollmann, Angela Hiesinger, Julia List, Jonatan Kendler, Thorsten Klampfl, Mehak Randhawa, Jana Trifinopoulos, Barbara Maurer, Reinhard Grausenburger, Christof A Bertram, Richard H Moriggl, Thomas Rülicke, Charles G Mullighan, Agnieszka Witalisz-Siepracka, Wencke Walter, Gregor Hoermann, Veronika Sexl, Dagmar Gotthardt
Patients with T- and NK-cell neoplasms frequently have somatic STAT5B gain-of-function mutations. The most frequent STAT5B mutation is STAT5BN642H, which is known to drive murine T-cell leukemia although its role in NK-cell malignancies is unclear. Introduction of the STAT5BN642H mutation into human NK-cell lines enhances their potential to induce leukemia in mice. We have generated a mouse model that enables tissue-specific expression of STAT5BN642H and have selectively expressed the mutated STAT5B in hematopoietic cells (N642Hvav/+) or exclusively in NK cells (N642HNK/NK)...
March 18, 2024: Blood
https://read.qxmd.com/read/38497939/serologic-response-to-the-epstein-barr-virus-peptidome-and-the-risk-for-multiple-sclerosis
#31
JOURNAL ARTICLE
Marianna Cortese, Yumei Leng, Kjetil Bjornevik, Moriah Mitchell, Brian C Healy, Michael J Mina, James D Mancuso, David W Niebuhr, Kassandra L Munger, Stephen J Elledge, Alberto Ascherio
IMPORTANCE: It remains unclear why only a small proportion of individuals infected with the Epstein-Barr virus (EBV) develop multiple sclerosis (MS) and what the underlying mechanisms are. OBJECTIVE: To assess the serologic response to all EBV peptides before the first symptoms of MS occur, determine whether the disease is associated with a distinct immune response to EBV, and evaluate whether specific EBV epitopes drive this response. DESIGN, SETTING, AND PARTICIPANTS: In this prospective, nested case-control study, individuals were selected among US military personnel with serum samples stored in the US Department of Defense Serum Repository...
March 18, 2024: JAMA Neurology
https://read.qxmd.com/read/38497827/sex-differences-and-driving-impairment-related-to-psychoactive-substances
#32
JOURNAL ARTICLE
Claudio Terranova, Clara Cestonaro, Alessandro Cinquetti, Federica Trevissoi, Donata Favretto, Guido Viel, Anna Aprile
OBJECTIVE: The first aim of the study was to identify sex differences in the use of psychoactive substances among subjects with a previous driving under the influence (DUI) episode. The secondary objective was to propose specific strategies for medico-legal improvements. METHODS: This was a retrospective observational study that took place between June 1, 2019, and August 31, 2023. It was conducted on DUI subjects examined for reinstatement of their driver's license using an integrated medico-legal and toxicological approach...
March 18, 2024: Traffic Injury Prevention
https://read.qxmd.com/read/38496464/major-alteration-of-lung-microbiome-and-the-host-reaction-in-critically-ill-covid-19-patients-with-high-viral-load
#33
Ingrid G Bustos, Rosana Wiscovitch-Russo, Harinder Singh, Benjamín L Sievers, Michele Matsuoka, Marcelo Freire, Gene S Tan, Mónica P Cala, Jose L Guerrero, Ignacio Martin-Loeches, Norberto Gonzalez-Juarbe, Luis Felipe Reyes
Background Patients with COVID-19 under invasive mechanical ventilation are at higher risk of developing ventilator-associated pneumonia (VAP), associated with increased healthcare costs, and unfavorable prognosis. The underlying mechanisms of this phenomenon have not been thoroughly dissected. Therefore, this study attempted to bridge this gap by performing a lung microbiota analysis and evaluating the host immune responses that could drive the development of VAP. Materials and methods In this prospective cohort study, mechanically ventilated patients with confirmed SARS-CoV-2 infection were enrolled...
March 8, 2024: Research Square
https://read.qxmd.com/read/38494143/tigar-reduces-neuronal-ferroptosis-by-inhibiting-succinate-dehydrogenase-activity-in-cerebral-ischemia
#34
JOURNAL ARTICLE
Xinxin Wang, Mei Li, Fan Wang, Guanghui Mao, Junchao Wu, Rong Han, Rui Sheng, Zhenghong Qin, Hong Ni
Ischemia Stroke (IS) is an acute neurological condition with high morbidity, disability, and mortality due to a severe reduction in local cerebral blood flow to the brain and blockage of oxygen and glucose supply. Oxidative stress induced by IS predisposes neurons to ferroptosis. TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits the intracellular glycolytic pathway to increase pentose phosphate pathway (PPP) flux, promotes NADPH production and thus generates reduced glutathione (GSH) to scavenge reactive oxygen species (ROS), and thus shows strong antioxidant effects to ameliorate cerebral ischemia/reperfusion injury...
March 15, 2024: Free Radical Biology & Medicine
https://read.qxmd.com/read/38492675/empagliflozin-and-pirfenidone-confer-renoprotection-through-suppression-of-glycogen-synthase-kinase-3%C3%AE-and-promotion-of-tubular-regeneration-in-rats-with-induced-metabolic-syndrome
#35
JOURNAL ARTICLE
Hoda E Mohamed, Merna A Abdelhady, Asmaa M Elmaghraby, Rania A Elrashidy
Metabolic syndrome (MetS) is largely coupled with chronic kidney disease (CKD). Glycogen synthase kinase-3β (GSK-3β) pathway drives tubular injury in animal models of acute kidney injury; but its contribution in CKD is still elusive. This study investigated the effect empagliflozin and/or pirfenidone against MetS-induced kidney dysfunction, and to clarify additional underpinning mechanisms particularly the GSK-3β signaling pathway. Adult male rats received 10%w/v fructose in drinking water for 20 weeks to develop MetS, then treated with either drug vehicle, empagliflozin (30 mg/kg/day) and/or pirfenidone (100 mg/kg/day) via oral gavage for subsequent 4 weeks, concurrently with the high dietary fructose...
March 14, 2024: Toxicology and Applied Pharmacology
https://read.qxmd.com/read/38491918/migration-inhibition-factor-secreted-by-peripheral-blood-memory-b-cells-binding-to-cd74-cd44-receptor-complex-drives-macrophage-behavior-in-alzheimer-s-disease
#36
JOURNAL ARTICLE
Bo Liu, Wei Luo, Ling Huang, Chunying Wei, Xiaorui Huang, Jun Liu, Ran Tao, Yingmin Mo, Xuebin Li
Dysregulation of the peripheral immune system is be involved in the neuroinflammation in Alzheimer disease (AD) and accelerate the disease progression. The contribution of immune cells, particularly B cells, to AD pathogenesis has gained attention in recent research. In this study, we investigated the role of Peripheral Blood Memory B cells (PBMBs) and their secreted Migration Inhibition Factor (MIF) in driving macrophage behavior in AD based on the scRNA-seq technique, immunofluorescence and flow cytometry...
2024: American Journal of Alzheimer's Disease and Other Dementias
https://read.qxmd.com/read/38490030/role-of-micrornas-as-post-transcription-regulators-of-matrix-metalloproteinases-and-their-association-in-tuberculous-meningitis
#37
JOURNAL ARTICLE
Apoorva Aggarwal, Neeraj Singla, Monidipa Konar, Maninder Kaur, Kusum Sharma, Kajal Jain, Manish Modi, Sadhna Sharma
Matrix metalloproteinases (MMPs) have a role in driving neuroinflammation in infectious as well as non-infectious diseases; however, recent reports have potentiated the role of microRNAs in regulating MMPs at post-transcriptional levels, leading to dysregulation of crucial MMP functions like tissue remodelling, blood brain barrier integrity, etc. In present study, microRNAs regulating MMPs (MMP2 and MMP3) were selected from database search followed by literature support. Expression of these microRNAs i.e., hsa-miR-495-3p, hsa-miR-132-3p and hsa-miR-21-5p was assessed by RT-PCR and the protein levels of MMPs were assessed by ELISA in the cerebrospinal fluid (CSF) of tuberculous meningitis (TBM) patients, healthy controls (HC) and non-infectious neuroinflammatory disease (NID) patients...
March 5, 2024: Tuberculosis
https://read.qxmd.com/read/38485359/the-effectiveness-of-regulations-preventing-alcohol-related-road-traffic-crashes-and-fatalities-in-the-european-union-countries
#38
JOURNAL ARTICLE
Janusz Kudła, Anna Podsiadło, Rafał Woźniak
INTRODUCTION: This article addresses the impact of policy measures on the number of alcohol-related crashes and fatalities in European Union countries. In particular, it assesses (1) whether mild or severe penalty measures should be used to reduce the number of crashes and fatalities caused by alcohol; and (2) whether alcoholic beverages should be treated differently or proportionally to their alcohol content. METHODS: This study analyzed the number of alcohol-related crashes and fatalities in 24 European Union countries between 2002 and 2014...
February 2024: Journal of Safety Research
https://read.qxmd.com/read/38484189/a-temporal-developmental-map-separates-human-nk-cells-from-non-cytotoxic-ilcs-through-clonal-and-single-cell-analysis
#39
JOURNAL ARTICLE
Dang Nghiem Vo, Ouyang Yuan, Minoru Kanaya, Gladys Telliam-Dushime, Hongzhe Li, Olga Kotova, Emel Caglar, Kristian Honnens de Lichtenberg, Shamim Herbert Rahman, Shamit Soneji, Stefan Scheding, David Bryder, Karl-Johan Malmberg, Ewa Sitnicka
Natural Killer (NK) cells represent the cytotoxic member within the innate lymphoid cell (ILC) family that are important against viral infections and cancer. While the NK cell emergence from hematopoietic stem and progenitor cells through multiple intermediate stages and the underlying regulatory gene network has been extensively studied in mouse, this process is not well characterized in human. Here, using a temporal in vitro model to reconstruct the developmental trajectory of NK lineage, we identified an ILC-restricted oligo-potent Stage 3a CD34-CD117+CD161+CD45RA+CD56- progenitor population, that exclusively gave rise to CD56-expressing ILCs in vitro...
March 14, 2024: Blood Advances
https://read.qxmd.com/read/38479999/brain-sodium-sensing-for-regulation-of-thirst-salt-appetite-and-blood-pressure
#40
REVIEW
Takeshi Y Hiyama
The brain possesses intricate mechanisms for monitoring sodium (Na) levels in body fluids. During prolonged dehydration, the brain detects variations in body fluids and produces sensations of thirst and aversions to salty tastes. At the core of these processes Nax , the brain's Na sensor, exists. Specialized neural nuclei, namely the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), which lack the blood-brain barrier, play pivotal roles. Within the glia enveloping the neurons in these regions, Nax collaborates with Na+ /K+ -ATPase and glycolytic enzymes to drive glycolysis in response to elevated Na levels...
March 2024: Physiological Reports
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