keyword
https://read.qxmd.com/read/38422186/transcriptome-analysis-reveals-enhancement-of-cardiogenesis-related-signaling-pathways-by-s-nitroso-n-pivaloyl-d-penicillamine-snpip-implications-for-improved-diastolic-function-and-cardiac-performance
#1
JOURNAL ARTICLE
Yasuhiro Takenaka, Masataka Hirasaki, Hidemasa Bono, Shigeo Nakamura, Yoshihiko Kakinuma
We previously reported a novel compound called S-nitroso-N-pivaloyl-D-penicillamine (SNPiP), which was screened from a group of nitric oxide (NO) donor compounds with a basic chemical structure of S-nitroso-N-acetylpenicillamine (SNAP), to activate the non-neuronal acetylcholine (NNA) system. SNPiP-treated mice exhibited improved cardiac output and enhanced diastolic function, without an increase in heart rate. The NNA-activating effects included increased resilience to ischemia, modulation of energy metabolism preference, and activation of angiogenesis...
February 29, 2024: Journal of Cardiovascular Pharmacology
https://read.qxmd.com/read/38306561/role-of-pax6-trpa1-bcl11b-mcoln2-cux1-emx1-in-colorectal-cancer-and-osteosarcoma
#2
JOURNAL ARTICLE
Jie Zhang, Qiang Gao, Shiyang Hou, Xiaoqian Chi, Meiliang Zheng, Qijun Zhang, Haifeng Shan, Xiaoyu Zhang, Chunbo Kang
Colorectal cancer is a cancer that arises from the abnormal growth of cells in the colon or rectum. Osteosarcoma (OS) is a common primary bone tumor with high degree of malignancy. The configuration files for colorectal cancer dataset GSE142279 and OS datasets GSE197158 and GSE206448 were downloaded from Gene Expression Omnibus database using the platforms GPL20795, GPL20301, and GPL24676. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis (WGCNA) was performed...
February 2, 2024: Medicine (Baltimore)
https://read.qxmd.com/read/38139811/a-critical-interpretive-synthesis-of-the-role-of-arecoline-in-oral-carcinogenesis-is-the-local-cholinergic-axis-a-missing-link-in-disease-pathophysiology
#3
REVIEW
Hakan Gocol, Jin Han Zeng, Sara Chang, Buo Yu Koh, Hoang Nguyen, Nicola Cirillo
Arecoline is the primary active carcinogen found in areca nut and has been implicated in the pathogenesis of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF). For this study, we conducted a stepwise review process by combining iterative scoping reviews with a post hoc search, with the aim of identifying the specific mechanisms by which arecoline initiates and promotes oral carcinogenesis. Our initial search allowed us to define the current trends and patterns in the pathophysiology of arecoline-induced OSF and OSCC, which include the induction of cell proliferation, facilitation of invasion, adhesion, and migration, increased collagen deposition and fibrosis, imbalance in immune and inflammatory mechanisms, and genotoxicity...
December 4, 2023: Pharmaceuticals
https://read.qxmd.com/read/38101565/lrp4-site-specific-variants-in-the-third-%C3%AE-propeller-domain-causes-congenital-myasthenic-syndrome-type-17
#4
JOURNAL ARTICLE
Tariq Al Jabry, Nadia Al-Hashmi, Basem Abdelhadi, Almundher Al-Maawali
LRP4 is expressed in many organs. It mediates SOST-dependent inhibition of bone formation and acts as an inhibitor of WNT signaling. It is also a postsynaptic end plate cell surface receptor at the neuromuscular junction and is central to its development, maintenance, and function. Pathogenic variants of LRP4 that specifically affect the canonical WNT signaling pathway are known to be associated with Cenani-Lenz syndactyly syndrome or the overlapping condition sclerosteosis. However, site-specific pathogenic variants of LRP4 have been associated with the congenital myasthenic syndrome (CMS) type 17 with no abnormal bone phenotype...
December 13, 2023: European Journal of Medical Genetics
https://read.qxmd.com/read/38040133/transcriptome-analysis-revealed-the-function-of-five-tandemly-duplicated-nachrs-in-the-transplantation-immunity-in-pearl-oyster-pinctada-fucata-martensii
#5
JOURNAL ARTICLE
Min Yang, Ming Zhang, Xin Lei Li, Yue Wen Deng, Yu Jiao
nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that play an important role in the homeostatic regulation of physiological functions. Our previous studies showed that nAChRs in the genome of pearl oyster Pinctada fucata martensii (PmnAChRs) were expanded through tandem duplication. This study aimed to analyze the function of five tandemly duplicated PmnAChRs in the transplantation immunity in P. f. martensii. Transcriptome analysis reveals that the differentially expressed genes (DEGs) shared between PmnAChR-RNAi and the control group were functionally involved in Signal transduction, Immune system et al...
November 29, 2023: Fish & Shellfish Immunology
https://read.qxmd.com/read/37994470/transcriptome-profile-of-subsynaptic-myonuclei-at-the-neuromuscular-junction-in-embryogenesis
#6
JOURNAL ARTICLE
Bisei Ohkawara, Masaomi Kurokawa, Akinori Kanai, Kiyomi Imamura, Guiying Chen, Ruchen Zhang, Akio Masuda, Koichi Higashi, Hiroshi Mori, Yutaka Suzuki, Ken Kurokawa, Kinji Ohno
Skeletal muscle fiber is a large syncytium with multiple and evenly distributed nuclei. Adult subsynaptic myonuclei beneath the neuromuscular junction (NMJ) express specific genes, the products of which coordinately function in the maintenance of the pre- and post-synaptic regions. However, the gene expression profiles that promote the NMJ formation during embryogenesis remain largely unexplored. We performed single-nucleus RNA sequencing (snRNA-seq) analysis of embryonic and neonatal mouse diaphragms, and found that each myonucleus had a distinct transcriptome pattern during the NMJ formation...
November 23, 2023: Journal of Neurochemistry
https://read.qxmd.com/read/36909191/canagliflozin-alleviates-valproic-acid-induced-autism-in-rat-pups-role-of-pten-pdk-ppar-%C3%AE-signaling-pathways
#7
JOURNAL ARTICLE
Mariam A Elgamal, Dina M Khodeer, Basel A Abdel-Wahab, Ibrahim Abdel Aziz Ibrahim, Abdullah R Alzahrani, Yasser M Moustafa, Azza A Ali, Norhan M El-Sayed
Autism is complex and multifactorial, and is one of the fastest growing neurodevelopmental disorders. Canagliflozin (Cana) is an antidiabetic drug that exhibits neuroprotective properties in various neurodegenerative syndromes. This study investigated the possible protective effect of Cana against the valproic acid (VPA)-induced model of autism. VPA was injected subcutaneously (SC) into rat pups at a dose of 300 mg/kg, twice daily on postnatal day-2 (PD-2) and PD-3, and once on PD-4 to induce an autism-like syndrome...
2023: Frontiers in Pharmacology
https://read.qxmd.com/read/36374861/vitamin-d-and-rosuvastatin-alleviate-type-ii-diabetes-induced-cognitive-dysfunction-by-modulating-neuroinflammation-and-canonical-noncanonical-wnt-%C3%AE-catenin-signaling
#8
JOURNAL ARTICLE
Muhammad Muneeb, Suzan M Mansou, Samira Saleh, Reham A Mohammed
BACKGROUND: Type-II diabetes mellitus (T2DM) is a major risk factor for cognitive impairment. Protecting the brain environment against inflammation, and neurodegeneration, as well as preservation of the BBB veracity through modulating the crosstalk between insulin/AKT/GSK-3β and Wnt/β-catenin signaling, might introduce novel therapeutic targets. PURPOSE: This study aimed at exploring the possible neuroprotective potential of vitamin D3 (VitD) and/or rosuvastatin (RSV) in T2DM-induced cognitive deficits...
2022: PloS One
https://read.qxmd.com/read/36323254/cholinergic-receptor-wnt-pathway-controls-immune-activation-by-sensing-intestinal-dysfunction
#9
JOURNAL ARTICLE
Jie Ren, Yu Sang, Alejandro Aballay
Alterations in the intestinal physiology caused by pathogen colonization result in immune activation. To provide insights into the mechanisms underlying the control of immune activation by changes in intestinal homeostasis, we conducted a forward genetic screen for suppressors of immune activation by intestinal distension in Caenorhabditis elegans. Our results indicate that C. elegans ACC-4, a member of a family of acetylcholine receptors, is required in immune activation by defects in the defecation motor program or by pathogen infection...
November 1, 2022: Cell Reports
https://read.qxmd.com/read/36048538/targeting-acetylcholine-signaling-modulates-persistent-drug-tolerance-in-egfr-mutant-lung-cancer-and-impedes-tumor-relapse
#10
JOURNAL ARTICLE
Meng Nie, Na Chen, Huanhuan Pang, Tao Jiang, Wei Jiang, Panwen Tian, LiAng Yao, Yangzi Chen, Ralph J DeBerardinis, Weimin Li, Qitao Yu, Caicun Zhou, Zeping Hu
Although first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy is effective for treating EGFR-mutant non-small cell lung cancer (NSCLC), it is now understood that drug-tolerant persister (DTP) cells escaping from initial treatment eventually drives drug resistance. Here, through integration of metabolomics and transcriptomics, we found that the neurotransmitter acetylcholine (ACh) was specifically accumulated in DTP cells, and illustrated that treatment with EGFR-TKI heightens the expression of the rate-limiting enzyme choline acetyltransferase (ChAT) in ACh biosynthesis via YAP mediation...
September 1, 2022: Journal of Clinical Investigation
https://read.qxmd.com/read/35758003/epigenetic-rewiring-of-pathways-related-to-odour-perception-in-immune-cells-exposed-to-sars-cov-2-in-vivo-and-in-vitro
#11
JOURNAL ARTICLE
Johanna Huoman, Shumaila Sayyab, Eirini Apostolou, Lovisa Karlsson, Lucas Porcile, Muhammad Rizwan, Sumit Sharma, Jyotirmoy Das, Anders Rosén, Maria Lerm
A majority of SARS-CoV-2 recoverees develop only mild-to-moderate symptoms, while some remain completely asymptomatic. Although viruses, including SARS-CoV-2, may evade host immune responses by epigenetic mechanisms including DNA methylation, little is known about whether these modifications are important in defence against and healthy recovery from COVID-19 in the host. To this end, epigenome-wide DNA methylation patterns from COVID-19 convalescents were compared to uninfected controls from before and after the pandemic...
December 2022: Epigenetics: Official Journal of the DNA Methylation Society
https://read.qxmd.com/read/35668264/boswellic-acids-ameliorate-neurodegeneration-induced-by-alcl-3-the-implication-of-wnt-%C3%AE-catenin-pathway
#12
JOURNAL ARTICLE
Eman A Mohamed, Hebatalla I Ahmed, Heba S Zaky, Amira M Badr
Alzheimer's disease (AD) is a neurodegenerative disease (ND) that represents the principal cause of dementia. Effective treatment is still lacking. Without prevention, Alzheimer's disease (AD) incidence is expected to triple within 30 years. The risk increases in highly polluted areas and is positively linked to chronic aluminum (Al) exposure. Canonical Wingless-Int (Wnt)/β-catenin pathway has been found to play a considerable role in ND pathogenesis. Resins of Boswellia serrata (frankincense) have been used traditionally for their psychoactive activity, in addition to their memory-boosting effects...
June 6, 2022: Environmental Science and Pollution Research International
https://read.qxmd.com/read/35606902/transcriptomic-analyses-of-neurod1-mediated-astrocyte-to-neuron-conversion
#13
JOURNAL ARTICLE
Ning-Xin Ma, Brendan Puls, Gong Chen
Ectopic expression of a single neural transcription factor NeuroD1 can reprogram reactive glial cells into functional neurons both in vitro and in vivo, but the underlying mechanisms are not well understood yet. Here, we used RNA-sequencing technology to capture the transcriptomic changes at different time points during the reprogramming process. We found that following NeuroD1 overexpression, astroglial genes (ACTG1, ALDH1A3, EMP1, CLDN6, SOX21) were significantly downregulated, whereas neuronal genes (DCX, RBFOX3/NeuN, CUX2, RELN, SNAP25) were significantly upregulated...
July 2022: Developmental Neurobiology
https://read.qxmd.com/read/35580169/the-cell-polarity-protein-vangl2-in-the-muscle-shapes-the-neuromuscular-synapse-by-binding-to-and-regulating-the-tyrosine-kinase-musk
#14
JOURNAL ARTICLE
Myriam Boëx, Steve Cottin, Marius Halliez, Stéphanie Bauché, Céline Buon, Nathalie Sans, Mireille Montcouquiol, Jordi Molgó, Muriel Amar, Arnaud Ferry, Mégane Lemaitre, Andrée Rouche, Dominique Langui, Asha Baskaran, Bertrand Fontaine, Julien Messéant, Laure Strochlic
The development of the neuromuscular junction (NMJ) requires dynamic trans-synaptic coordination orchestrated by secreted factors, including Wnt family morphogens. To investigate how these synaptic cues in NMJ development are transduced, particularly in the regulation of acetylcholine receptor (AChR) accumulation in the postsynaptic membrane, we explored the function of Van Gogh-like protein 2 (Vangl2), a core component of Wnt planar cell polarity signaling. We found that conditional, muscle-specific ablation of Vangl2 in mice reproduced the NMJ differentiation defects seen in mice with global Vangl2 deletion...
May 17, 2022: Science Signaling
https://read.qxmd.com/read/35370785/mechanistic-clues-provided-by-concurrent-changes-in-the-expression-of-genes-encoding-the-m-1-muscarinic-receptor-%C3%AE-catenin-signaling-proteins-and-downstream-targets-in-adenocarcinomas-of-the-colon
#15
JOURNAL ARTICLE
Madeline Alizadeh, Alyssa Schledwitz, Kunrong Cheng, Jean-Pierre Raufman
Muscarinic receptors (MRs) in the G protein-coupled receptor superfamily are recipients and mediators of parasympathetic neural transmission within the central and enteric nervous systems. MR subtypes, M1 R-M5 R, encoded by CHRM1-CHRM5 , expressed widely throughout the gastrointestinal (GI) tract, modulate a range of critical, highly regulated activities in healthy tissue, including secretion, motility, and cellular renewal. CHRM3 /M3 R overexpression in colon cancer is associated with increased cell proliferation, metastasis, and a worse outcome, but little is known about the role of the other four muscarinic receptor subtypes...
2022: Frontiers in Physiology
https://read.qxmd.com/read/35146638/molecular-dynamics-and-structure-based-virtual-screening-and-identification-of-natural-compounds-as-wnt-signaling-modulators-possible-therapeutics-for-alzheimer-s-disease
#16
JOURNAL ARTICLE
Suman Manandhar, Runali Sankhe, Keerthi Priya, Gangadhar Hari, Harish Kumar B, Chetan H Mehta, Usha Y Nayak, K Sreedhara Ranganath Pai
Wnt signaling pathway is an evolutionarily conserved pathway responsible for neurogenesis, axon outgrowth, neuronal polarity, synapse formation, and maintenance. Downregulation of Wnt signaling has been found in patients with Alzheimer's disease (AD). Several experimental approaches to activate Wnt signaling pathway have proven to be beneficial in alleviating AD, which is one of the new therapeutic approaches for AD. The current study focuses on the computational structure-based virtual screening followed by the identification of potential phytomolecules targeting different markers of Wnt signaling like WIF1, DKK1, LRP6, GSK-3β, and acetylcholine esterase...
February 11, 2022: Molecular Diversity
https://read.qxmd.com/read/35093471/dapagliflozin-diminishes-memory-and-cognition-impairment-in-streptozotocin-induced-diabetes-through-its-effect-on-wnt-%C3%AE-catenin-and-creb-pathway
#17
JOURNAL ARTICLE
Hala El-Safty, Ashraf Ismail, Rania Mohsen, Ayman E El-Sahar, Muhammed A Saad
Diabetic neuropathy is a chronic condition that affects a significant number of individuals with diabetes. Streptozotocin injection intraperitoneally to rodents produces pancreatic islet β-cell destruction causing hyperglycemia, which affect the brain leading to memory and cognition impairment. Dapagliflozin may be able to reverse beta-cell injury and alleviate this impairment. This effect may be via neuroprotective effect or possible involvement of the antioxidant, and anti-apoptotic properties. Forty rats were divided into four groups as follows: The normal control group, STZ-induced diabetes group, STZ-induced diabetic rats followed by treatment with oral dapagliflozin group and normal rats treated with oral dapagliflozin...
January 27, 2022: Brain Research Bulletin
https://read.qxmd.com/read/34944540/transport-and-secretion-of-the-wnt3-ligand-by-motor-neuron-like-cells-and-developing-motor-neurons
#18
JOURNAL ARTICLE
Cristina Pinto, Viviana Pérez, Jessica Mella, Miguel Albistur, Teresa Caprile, Francisca C Bronfman, Juan Pablo Henríquez
The vertebrate neuromuscular junction (NMJ) is formed by a presynaptic motor nerve terminal and a postsynaptic muscle specialization. Cumulative evidence reveals that Wnt ligands secreted by the nerve terminal control crucial steps of NMJ synaptogenesis. For instance, the Wnt3 ligand is expressed by motor neurons at the time of NMJ formation and induces postsynaptic differentiation in recently formed muscle fibers. However, the behavior of presynaptic-derived Wnt ligands at the vertebrate NMJ has not been deeply analyzed...
December 17, 2021: Biomolecules
https://read.qxmd.com/read/34708522/licl-attenuates-impaired-learning-and-memory-of-app-ps1-mice-which-in-mechanism-involves-%C3%AE-7-nachrs-and-wnt-%C3%AE-catenin-pathway
#19
JOURNAL ARTICLE
Jie Xiang, Long-Yan Ran, Xiao-Xiao Zeng, Wen-Wen He, Yi Xu, Kun Cao, Yang-Ting Dong, Xiao-Lan Qi, Wen-Feng Yu, Yan Xiao, Zhi-Zhong Guan
We examined the mechanism by which lithium chloride (LiCl) attenuates the impaired learning capability and memory function of dual-transgenic APP/PS1 mice. Six- or 12-month-old APP/PS1 and wild-type (WT) mice were randomized into four groups, namely WT, WT+Li (100 mg LiCl/kg body weight, gavage once daily), APP/PS1 and APP/PS1+Li. Primary rat hippocampal neurons were exposed to β-amyloid peptide oligomers (AβOs), LiCl and/or XAV939 (inhibitor of Wnt/β-catenin) or transfected with small interfering RNA against the β-catenin gene...
October 28, 2021: Journal of Cellular and Molecular Medicine
https://read.qxmd.com/read/34631692/human-three-finger-protein-lypd6-is-a-negative-modulator-of-the-cholinergic-system-in-the-brain
#20
JOURNAL ARTICLE
Dmitrii Kulbatskii, Zakhar Shenkarev, Maxim Bychkov, Eugene Loktyushov, Mikhail Shulepko, Sergey Koshelev, Igor Povarov, Alexander Popov, Steve Peigneur, Anton Chugunov, Sergey Kozlov, Irina Sharonova, Roman Efremov, Vladimir Skrebitsky, Jan Tytgat, Mikhail Kirpichnikov, Ekaterina Lyukmanova
Lypd6 is a GPI-tethered protein from the Ly-6/uPAR family expressed in the brain. Lypd6 enhances the Wnt/β-catenin signaling, although its action on nicotinic acetylcholine receptors (nAChRs) have been also proposed. To investigate a cholinergic activity of Lypd6, we studied a recombinant water-soluble variant of the human protein (ws-Lypd6) containing isolated "three-finger" LU-domain. Experiments at different nAChR subtypes expressed in Xenopus oocytes revealed the negative allosteric modulatory activity of ws-Lypd6...
2021: Frontiers in Cell and Developmental Biology
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