keyword
https://read.qxmd.com/read/38652712/hgclamir-hypergraph-contrastive-learning-with-attention-mechanism-and-integrated-multi-view-representation-for-predicting-mirna-disease-associations
#21
JOURNAL ARTICLE
Dong Ouyang, Yong Liang, Jinfeng Wang, Le Li, Ning Ai, Junning Feng, Shanghui Lu, Shuilin Liao, Xiaoying Liu, Shengli Xie
Existing studies have shown that the abnormal expression of microRNAs (miRNAs) usually leads to the occurrence and development of human diseases. Identifying disease-related miRNAs contributes to studying the pathogenesis of diseases at the molecular level. As traditional biological experiments are time-consuming and expensive, computational methods have been used as an effective complement to infer the potential associations between miRNAs and diseases. However, most of the existing computational methods still face three main challenges: (i) learning of high-order relations; (ii) insufficient representation learning ability; (iii) importance learning and integration of multi-view embedding representation...
April 2024: PLoS Computational Biology
https://read.qxmd.com/read/38652703/comprehensive-analysis-of-immune-signatures-in-primary-biliary-cholangitis-and-autoimmune-hepatitis
#22
JOURNAL ARTICLE
Xiaoxue Yang, Jiawei Li, Meiling Ren, Xuemei Pan, Huiling Liu, Jie Jiang, Man Li, Zhe Yang, Bingyu Han, Lina Ma, Jianlei Hao, Yuanyuan Duan, Zhinan Yin, Yan Xu, Zheng Xiang, Bin Wu
Primary Biliary Cholangitis (PBC) and Autoimmune Hepatitis (AIH) are autoimmune diseases that target hepatocytes and bile duct cells, respectively. Despite their shared autoimmune nature, the differences in immunologic characteristics between them remain largely unexplored. This study seeks to elucidate the unique immunological profiles of PBC and AIH, and to identify key differences. We comprehensively analyzed various T-cell subsets and their receptor expression in a cohort of 45 patients, including 27 PBC and 18 AIH cases...
April 23, 2024: Journal of Leukocyte Biology
https://read.qxmd.com/read/38652699/lack-of-mtorc2-signalling-in-cd11c-myeloid-cells-inhibits-their-migration-and-ameliorates-experimental-colitis
#23
JOURNAL ARTICLE
Aline Ignacio, Marcella Cipelli, Tatiane Takiishi, Cristhiane Favero Aguiar, Fernanda Fernandes Terra, Bruno Ghirotto, Eloisa Martins Silva, Angela Castoldi, Yuli Thamires Magalhães, Tiago Antonio, Barbara Nunes Padovani, Meire Ioshie Hiyane, Vinicius Andrade-Oliveira, Fabio Luis Forti, Niels Olsen Saraiva Camara
The Mammalian Target of Rapamycin (mTOR) pathway plays a key role in determining immune cells function through modulation of their metabolic status. By specific deletion of Rictor in CD11c+ myeloid cells (referred to here as CD11cRicΔ/Δ), this study investigated the role of mTOR complex 2 (mTORC2) signalling in dendritic cells (DCs) function in mice. We showed that upon DSS-induced colitis, lack of mTORC2 signalling CD11c+ cells diminishes colitis score, and abrogates dendritic cell (DC) migration to the mesenteric lymph nodes (MLN), thereby diminishing the infiltration of T helper (Th) 17 cells in the lamina propria (LP) and subsequent inflammation...
April 23, 2024: Journal of Leukocyte Biology
https://read.qxmd.com/read/38652684/expression-of-syo_1-56-sarp-regulator-unveils-potent-elasnin-derivatives-with-antibacterial-activity
#24
JOURNAL ARTICLE
Islam A Abdelhakim, Yushi Futamura, Yukihiro Asami, Hideaki Hanaki, Naoko Kito, Sachiko Masuda, Arisa Shibata, Atsuya Muranaka, Hiroyuki Koshino, Ken Shirasu, Hiroyuki Osada, Jun Ishikawa, Shunji Takahashi
Actinomycetes are prolific producers of natural products, particularly antibiotics. However, a significant proportion of its biosynthetic gene clusters (BGCs) remain silent under typical laboratory conditions. This limits the effectiveness of conventional isolation methods for the discovery of novel natural products. Genetic interventions targeting the activation of silent gene clusters are necessary to address this challenge. Streptomyces antibiotic regulatory proteins (SARPs) act as cluster-specific activators and can be used to target silent BGCs for the discovery of new antibiotics...
April 23, 2024: Journal of Natural Products
https://read.qxmd.com/read/38652683/chemical-genetics-in-c-elegans-identifies-anticancer-mycotoxins-chaetocin-and-chetomin-as-potent-inducers-of-a-nuclear-metal-homeostasis-response
#25
JOURNAL ARTICLE
Elijah Abraham, A M Gihan K Athapaththu, Kalina R Atanasova, Qi-Yin Chen, Taylor J Corcoran, Juan Piloto, Cheng-Wei Wu, Ranjala Ratnayake, Hendrik Luesch, Keith P Choe
C. elegans numr-1/2 (<u>nu</u>clear-localized <u>m</u>etal-<u>r</u>esponsive) is an identical gene pair encoding a nuclear protein previously shown to be activated by cadmium and disruption of the integrator RNA metabolism complex. We took a chemical genetic approach to further characterize regulation of this novel metal response by screening 41,716 compounds and extracts for numr-1p::GFP activation. The most potent activator was chaetocin, a fungal 3,6-epidithiodiketopiperazine (ETP) with promising anticancer activity...
April 23, 2024: ACS Chemical Biology
https://read.qxmd.com/read/38652680/the-h3k4-demethylase-jmj1-is-required-for-proper-timing-of-flowering-in-brachypodium-distachyon
#26
JOURNAL ARTICLE
Bing Liu, Chengzhang Li, Xiang Li, Jiachen Wang, Wenhao Xie, Daniel P Woods, Weiya Li, Xiaoyu Zhu, Shuoming Yang, Aiwu Dong, Richard M Amasino
Flowering is a key developmental transition in the plant life cycle. In temperate climates, flowering often occurs in response to the perception of seasonal cues such as changes in day-length and temperature. However, the mechanisms that have evolved to control the timing of flowering in temperate grasses are not fully understood. We identified a Brachypodium distachyon mutant whose flowering is delayed under inductive long-day conditions due to a mutation in the JMJ1 gene, which encodes a Jumonji domain-containing protein...
April 23, 2024: Plant Cell
https://read.qxmd.com/read/38652667/an-artificial-neural-network-based-approach-for-predicting-the-proton-beam-spot-dosimetric-characteristics-of-a-pencil-beam-scanning-technique
#27
JOURNAL ARTICLE
C P Ranjith, Mayakannan Krishnan, Vysakh Raveendran, Lalit Chaudhari, Siddhartha Laskar
Utilising Machine Learning (ML) models to predict dosimetric parameters in pencil beam scanning proton therapy presents a promising and practical approach. The study developed Artificial Neural Network (ANN) models to predict proton beam spot size and relative positional errors using 9000 proton spot data. The irradiation log files as input variables and corresponding scintillation detector measurements as the label values. The ANN models were developed to predict six variables: spot size in the x -axis, y -axis, major axis, minor axis, and relative positional errors in the x -axis and y -axis...
April 22, 2024: Biomedical Physics & Engineering Express
https://read.qxmd.com/read/38652659/hsv-1-employs-ul56-to-antagonize-expression-and-function-of-cgamp-channels
#28
JOURNAL ARTICLE
Henry T W Blest, Alexander Redmond, Jed Avissar, Jake Barker, Anne Bridgeman, Gerissa Fowler, Lise Chauveau, Jonny Hertzog, Iolanda Vendrell, Roman Fischer, Marie B Iversen, Lichen Jing, David M Koelle, Søren R Paludan, Benedikt M Kessler, Colin M Crump, Jan Rehwinkel
DNA sensing is important for antiviral immunity. The DNA sensor cGAS synthesizes 2'3'-cyclic GMP-AMP (cGAMP), a second messenger that activates STING, which induces innate immunity. cGAMP not only activates STING in the cell where it is produced but cGAMP also transfers to other cells. Transporters, channels, and pores (including SLC19A1, SLC46A2, P2X7, ABCC1, and volume-regulated anion channels (VRACs)) release cGAMP into the extracellular space and/or import cGAMP. We report that infection with multiple human viruses depletes some of these cGAMP conduits...
April 22, 2024: Cell Reports
https://read.qxmd.com/read/38652652/downregulation-of-glis3-in-ins1-cells-exposed-to-chronically-elevated-glucose-contributes-to-glucotoxicity-associated-%C3%AE-cell-dysfunction
#29
JOURNAL ARTICLE
LilyAnne M Grieve, Abhya Rani, Gary T ZeRuth
Chronically elevated levels of glucose are deleterious to pancreatic β cells and contribute to β cell dysfunction, which is characterized by decreased insulin production and a loss of β cell identity. The Krüppel-like transcription factor, Glis3 has previously been shown to positively regulate insulin transcription and mutations within the Glis3 locus have been associated with the development of several pathologies including type 2 diabetes mellitus. In this report, we show that Glis3 is significantly downregulated at the transcriptional level in INS1 832/13 cells within hours of being subjected to high glucose concentrations and that diminished expression of Glis3 is at least partly attributable to increased oxidative stress...
December 31, 2024: Islets
https://read.qxmd.com/read/38652648/short-term-effect-of-pre-operative-anti-vegf-on-angiogenic-and-fibrotic-profile-of-fibrovascular-membranes-of-proliferative-diabetic-retinopathy
#30
JOURNAL ARTICLE
Kaveh Fadakar, Safa Rahmani, Thomas Tedeschi, Jeremy A Lavine, Amani A Fawzi
PURPOSE: Adjuvant, pre-operative intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have been used to reduce peri-operative bleeding in eyes undergoing pars-plana vitrectomy for complications of proliferative diabetic retinopathy (PDR). To address the concern over their potential off-target effects of progressive fibrous contraction, we sought to dissect the transcriptional changes in the surgically extracted fibrovascular membranes (FVMs). METHODS: We analyzed surgically extracted FVMs from 10 eyes: 4 eyes pretreated with intravitreal bevacizumab (IVB) and 6 untreated eyes...
April 1, 2024: Investigative Ophthalmology & Visual Science
https://read.qxmd.com/read/38652598/notch1-hyperactivity-drives-ubiquitination-of-nox2-and-dysfunction-of-cd8-regulatory-t-cells-in-patients-with-systemic-lupus-erythematosus
#31
JOURNAL ARTICLE
Zixin Yuan, Mengdi Liu, Lei Zhang, Li Jia, Siao Hao, Danhua Su, Longhai Tang, Chunhong Wang, Mingyuan Wang, Zhenke Wen
OBJECTIVES: Patients with systemic lupus erythematosus (SLE) display heightened immune activation and elevated IgG autoantibody levels, indicating compromised regulatory T cell (Tregs) function. Our recent findings pinpoint CD8+ Tregs as crucial regulators within secondary lymphoid organs, operating in a NOX2-dependent mechanism. However, the specific involvement of CD8+ Tregs in SLE pathogenesis and the mechanisms underlying their role remain uncertain. METHODS: SLE and healthy individuals were enlisted to assess the quantity and efficacy of Tregs...
April 23, 2024: Rheumatology
https://read.qxmd.com/read/38652563/nr2e3-loss-disrupts-photoreceptor-cell-maturation-and-fate-in-human-organoid-models-of-retinal-development
#32
JOURNAL ARTICLE
Nathaniel K Mullin, Laura R Bohrer, Andrew P Voigt, Lola P Lozano, Allison T Wright, Vera L Bonilha, Robert F Mullins, Edwin M Stone, Budd A Tucker
While dysfunction and death of light-detecting photoreceptor cells underlie most inherited retinal dystrophies, knowledge of the species-specific details of human rod and cone photoreceptor cell development remains limited. Here, we generate retinal organoids carrying retinal disease-causing variants in NR2E3, as well as isogenic and unrelated controls. Organoids were sampled using single-cell RNA sequencing across the developmental window encompassing photoreceptor specification, emergence, and maturation...
April 23, 2024: Journal of Clinical Investigation
https://read.qxmd.com/read/38652558/a-tryptophan-derived-uremic-metabolite-ahr-pdk4-axis-governs-skeletal-muscle-mitochondrial-energetics-in-chronic-kidney-disease
#33
JOURNAL ARTICLE
Trace Thome, Nicholas A Vugman, Lauren E Stone, Keon Wimberly, Salvatore T Scali, Terence E Ryan
Chronic kidney disease (CKD) causes an accumulation of uremic metabolites that negatively impact skeletal muscle function. Tryptophan-derived uremic metabolites are agonists of the aryl hydrocarbon receptor (AHR) which has been shown to be activated in the blood of CKD patients. This study investigated the role of the AHR in skeletal muscle pathology of CKD. Compared to control participants with normal kidney function, AHR-dependent gene expression (CYP1A1 and CYP1B1) was significantly upregulated in skeletal muscle of patients with CKD (P=0...
April 23, 2024: JCI Insight
https://read.qxmd.com/read/38652556/macrophage-derived-exosomal-mirna-141-triggers-endothelial-cell-pyroptosis-by-targeting-nlrp3-to-accelerate-sepsis-progression
#34
JOURNAL ARTICLE
Feng Zhan, Jun Zhang, Ping He, Wenteng Chen, Yanhong Ouyang
Sepsis, critical condition marked by severe organ dysfunction from uncontrolled infection, involves the endothelium significantly. Macrophages, through paracrine actions, play a vital role in sepsis, but their mechanisms in sepsis pathogenesis remain elusive. Objective: We aimed to explore how macrophage-derived exosomes with low miR-141 expression promote pyroptosis in endothelial cells (ECs). Exosomes from THP-1 cell supernatant were isolated and characterized. The effects of miR-141 mimic/inhibitor on apoptosis, proliferation, and invasion of Human Umbilical Vein Endothelial Cells (HUVECs) were assessed using flow cytometry, CCK-8, and transwell assays...
2024: International Journal of Immunopathology and Pharmacology
https://read.qxmd.com/read/38652555/a-genome-wide-association-study-identified-ptpn2-as-a-population-specific-susceptibility-gene-locus-for-primary-biliary-cholangitis
#35
JOURNAL ARTICLE
Yuki Hitomi, Kazuko Ueno, Yoshihiro Aiba, Nao Nishida, Michihiro Kono, Mitsuki Sugihara, Yosuke Kawai, Minae Kawashima, Seik-Soon Khor, Kazuhiro Sugi, Hirotaka Kouno, Hiroshi Kouno, Atsushi Naganuma, Satoru Iwamoto, Shinji Katsushima, Kiyoshi Furuta, Toshiki Nikami, Tomohiko Mannami, Tsutomu Yamashita, Keisuke Ario, Tatsuji Komatsu, Fujio Makita, Masaaki Shimada, Noboru Hirashima, Shiro Yokohama, Hideo Nishimura, Rie Sugimoto, Takuya Komura, Hajime Ota, Motoyuki Kojima, Makoto Nakamuta, Naoyuki Fujimori, Kaname Yoshizawa, Yutaka Mano, Hironao Takahashi, Kana Hirooka, Satoru Tsuruta, Takeaki Sato, Kazumi Yamasaki, Yuki Kugiyama, Yasuhide Motoyoshi, Tomoyuki Suehiro, Akira Saeki, Kosuke Matsumoto, Shinya Nagaoka, Seigo Abiru, Hiroshi Yatsuhashi, Masahiro Ito, Kazuhito Kawata, Akinobu Takaki, Kuniaki Arai, Teruko Arinaga, Masanori Abe, Masaru Harada, Makiko Taniai, Mikio Zeniya, Hiromasa Ohira, Shinji Shimoda, Atsumasa Komori, Atsushi Tanaka, Kazuyoshi Ishigaki, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura
BACKGROUND AIMS: Previous genome-wide association studies (GWAS) have indicated the involvement of shared (population-non-specific) and non-shared (population-specific) susceptibility genes in the pathogenesis of primary biliary cholangitis (PBC) among European and East-Asian populations. Although a meta-analysis of these distinct populations has recently identified more than 20 novel PBC susceptibility loci, analyses of population-specific genetic architecture are still needed for a more comprehensive search for genetic factors in PBC...
April 23, 2024: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://read.qxmd.com/read/38652550/human-nlrc4-promotes-cancer-survival-and-is-associated-to-type-i-interferon-signaling-and-immune-infiltration
#36
JOURNAL ARTICLE
Charlotte Domblides, Steven Crampton, Hong Liu, Juliet M Bartleson, Annie Nguyen, Claudia Champagne, Emily E Landy, Lindsey Spiker, Christopher Proffitt, Sunil Bhattarai, Anissa P Grawe, Matias Fuentealba Valenzuela, Lydia Lartigue, Isabelle Mahouche, Jeremy Dupaul-Chicoine, Kazuho Nishimura, Félix Lefort, Marie Decraecker, Valérie Velasco, Sonia Netzer, Vincent Pitard, Christian Roy, Isabelle Soubeyran, Victor Racine, Patrick Blanco, Julie Déchanet-Merville, Maya Saleh, Scott W Canna, David Furman, Benjamin Faustin
The immune system can control cancer progression. However, even though some innate immune sensors of cellular stress are expressed intrinsically in epithelial cells, their potential role in cancer aggressiveness and subsequent overall survival in humans is mainly unknown. Here, we show that NLR family CARD Domain Containing 4 (NLRC4) is downregulated in epithelial tumor cells of colorectal cancer (CRC) patients by using spatial tissue imaging. Strikingly, only the loss of tumor NLRC4 but not stromal is associated with poor immune infiltration (mainly dendritic and CD4+/CD8+ T cells) and accurately predicts progression to metastatic Stage IV and decrease of overall survival...
April 23, 2024: Journal of Clinical Investigation
https://read.qxmd.com/read/38652546/threonine-dehydrogenase-regulates-neutrophil-homeostasis-but-not-h3k4me3-levels-in-zebrafish
#37
JOURNAL ARTICLE
Ning-Zhe Li, Zi-Xuan Wang, Fan Zhang, Chang-Zhou Feng, Yi Chen, Dian-Jia Liu, Shu-Bei Chen, Yi Jin, Yuan-Liang Zhang, Yin-Yin Xie, Qiu-Hua Huang, Lan Wang, Bing Li, Xiao-Jian Sun
l-threonine dehydrogenase (Tdh) is an enzyme that links threonine metabolism to epigenetic modifications and mitochondria biogenesis. In vitro studies show that it is critical for the regulation of trimethylation of histone H3 lysine 4 (H3K4me3) levels and cell fate determination of mouse embryonic stem cells (mESCs). However, whether Tdh regulates a developmental process in vivo and, if it does, whether it also primarily regulates H3K4me3 levels in this process as it does in mESCs, remains elusive. Here, we revealed that, in zebrafish hematopoiesis, tdh is preferentially expressed in neutrophils...
April 23, 2024: FEBS Journal
https://read.qxmd.com/read/38652545/spatiotemporal-landscape-of-kidney-tubular-responses-to-glomerular-proteinuria
#38
JOURNAL ARTICLE
Anna Faivre, Milica Bugarski, Anna Rinaldi, Imene B Sakhi, Thomas Verissimo, David Legouis, Sara Correia, Monika Kaminska, Delal Dalga, Daniele Malpetti, Pietro E Cippa, Sophie de Seigneux, Andrew M Hall
BACKGROUND: Large increases in glomerular protein filtration induce major changes in body homeostasis and increase risk of kidney functional decline and cardiovascular disease. We investigated how elevated protein exposure modifies the landscape of tubular function along the entire nephron, to understand the cellular changes that mediate these important clinical phenomena. METHODS: We conducted single nuclei RNA sequencing, functional intravital imaging, and antibody staining to spatially map transport processes along the mouse kidney tubule...
April 24, 2024: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/38652543/endothelial-hif%C3%AE-pdgf-b-to-smooth-muscle-beclin1-signaling-sustains-pathological-muscularization-in-pulmonary-hypertension
#39
JOURNAL ARTICLE
Fatima Z Saddouk, Andrew P Kuzemczak, Junichi Saito, Daniel M Greif
Mechanisms underlying maintenance of pathological vascular hypermuscularization are poorly delineated. Herein, we investigated retention of smooth muscle cells (SMCs) coating normally unmuscularized distal pulmonary arterioles in pulmonary hypertension (PH) mediated by chronic hypoxia ± Sugen 5416, and reversal of this pathology. With hypoxia in mice or culture, lung endothelial cells (ECs) upregulated hypoxia-inducible factor (Hif)-1a and 2a which induce platelet-derived growth factor-B (PDGF-B), and these factors reduced to normoxic levels with re-normoxia...
April 23, 2024: JCI Insight
https://read.qxmd.com/read/38652538/hepatic-hif2-is-a-key-determinant-of-manganese-excess-and-polycythemia-in-slc30a10-deficiency
#40
JOURNAL ARTICLE
Milankumar Prajapati, Jared Z Zhang, Lauren Chiu, Grace S Chong, Courtney J Mercadante, Heather L Kowalski, Bradley S Delaney, Jessica A Anderson, Shuling Guo, Mariam Aghajan, Thomas B Bartnikas
Manganese is an essential yet potentially toxic metal. Initially reported in 2012, mutations in SLC30A10 are the first known inherited cause of manganese excess. SLC30A10 is an apical membrane protein that exports manganese from hepatocytes into bile and from enterocytes into the lumen of the gastrointestinal tract. SLC30A10 deficiency results in impaired gastrointestinal manganese excretion, leading to manganese excess, neurologic deficits, liver cirrhosis, polycythemia, and erythropoietin excess. Neurologic and liver disease are attributed to manganese toxicity...
April 23, 2024: JCI Insight
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