mapk signalling path

Infantile fibrosarcomas (IFS) and congenital mesoblastic nephroma (CMN) are rare myofibroblastic tumors of infancy and early childhood commonly harboring the ETV6::NTRK3 gene fusion. IFS/CMN are considered as tumors with an 'intermediate prognosis' as they are locally aggressive, but rarely metastasize, and generally have a favorable outcome. A fraction of IFS/CMN-related neoplasms are negative for the ETV6::NTRK3 gene rearrangement and are characterized by other chimeric proteins promoting MAPK signaling upregulation...

The consistent notion holds that hepatocellular carcinoma (HCC) initiation, progression, and clinical treatment failure treatment failure are affected by the accumulation of various genetic and epigenetic alterations. MicroRNAs (miRNAs) play an irreplaceable role in a variety of physiological and pathological states. meanwhile, epithelial-mesenchymal transition (EMT) is a crucial biological process that controls the development of HCC. miRNAs regulate the intermediation state of EMTor mesenchymal-epithelial transition (MTE)thereby regulating HCC progression...

Background: Alchornea laxiflora (Benth.) Pax & K. Hoffm. (A. laxiflora) has been indicated in traditional medicine to treat depression. However, scientific rationalization is still lacking. Hence, this study aimed to investigate the antidepressant potential of A. laxiflora using network pharmacology and molecular docking analysis. Materials and methods: The active compounds and potential targets of A. laxiflora and depression-related targets were retrieved from public databases, such as PubMed, PubChem, DisGeNET, GeneCards, OMIM, SwissTargetprediction, BindingDB, STRING, and DAVID...

The biological mechanism of action of platelet-rich plasma (PRP) in the treatment of temporomandibular joint (TMJ) osteoarthritis remains unclear. This study explored the mechanisms underlying interleukin (IL)-1β-induced inflammation and investigated the effect of PRP on TMJ condylar chondrocytes. Primary chondrocytes were isolated from the TMJ condyle of 4-week-old rats, and differentially expressed genes among three treatment groups (phosphate-buffered saline [control], IL-1β, and IL-1β + PRP) were identified using RNA-seq and characterized using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes path-enrichment analyses...

BACKGROUND: Lactobacillus casei possesses many kinds of bioactivities, such as anti-inflammation and anti-oxidant, and has been applied to treating multiple inflammatory diseases. However, its role in mastitis prevention has remained ambiguous. METHODS: This study aimed to examine the mechanisms underlying the preventive effects of L. casei 03 against E. coli- mastitis utilizing bovine mammary epithelial cells (BMECs) and a mouse model. RESULTS: In vitro assays revealed pretreatment with L...

Eph receptors are ubiquitous class of transmembrane receptors that mediate cell-cell communication, proliferation, differentiation, and migration. EphA1 receptors specifically play an important role in angiogenesis, fetal development, and cancer progression; however, studies of this receptor can be challenging as its ligand, ephrinA1, binds and activates several EphA receptors simultaneously. Optogenetic strategies could be applied to circumvent this requirement for ligand activation and enable selective activation of the EphA1 subtype...

Background Exposure to electronic cigarette (e-cigarette) aerosol has been linked to several health concerns, including DNA damage, elevated oxidative stress, the release of inflammatory cytokine, and dysfunctions in epithelial barriers. However, little is known about the effect of exclusive e-cigarette use on expression profiles of exosomal miRNAs, which play critical regulatory roles in many inflammatory responses and disease processes including cancer. We aim to compare the exosomal microRNA expression profile between exclusive e-cigarette users and normal controls without any tobacco product use (non-users)...

Neurodegenerative disorders are a debilitating and persistent threat to the global elderly population, carrying grim outcomes. Their genesis is often multifactorial, with a history of prior exposure to xenobiotics such as pesticides, heavy metals, enviornmental pollutants, ionizing radiation etc,. A holistic molecular insight into their mechanistic induction upon single or combinatorial exposure to different toxicants is still unclear. In the present study, one-month-old C57BL/6 male mice were administered orally with malathion (50 mg/kg body wt...

Heterozygous deleterious variants in SKI cause Shprintzen-Goldberg Syndrome, which is mainly characterized by craniofacial features, neurodevelopmental disorder and thoracic aorta dilatations/aneurysms. The encoded protein is a member of the transforming growth factor beta signaling. Paucity of reported studies exploring the SGS molecular pathogenesis hampers disease recognition and clinical interpretation of private variants. Here, the unpublished c.349G>A, p.[Gly117Ser] and the recurrent c.539C>T, p...

The advent of high throughput DNA sequencing is providing massive amounts of tumor-associated mutation data. Implicit in these analyses is the assumption that, by acquiring a series of hallmark changes, normal cells evolve along a neoplastic path. However, the lack of correlation between cancer risk and global exposure to mutagenic factors provides arguments against this model. This suggested that additional, non-mutagenic factors are at work in cancer development. A candidate determinant is TROP2 , that stands out for its expression in the majority of solid tumors in human, for its impact on the prognosis of most solid cancers and for its role as driver of cancer growth and metastatic diffusion, through overexpression as a wild-type form...

Tissue factor (TF) is a protein that plays a critical role in blood clotting, but recent research has also shown its involvement in cancer development and progression. Herein, we provide an overview of the structure of TF and its involvement in signaling pathways that promote cancer cell proliferation and survival, such as the PI3K/AKT and MAPK pathways. TF overexpression is associated with increased tumor aggressiveness and poor prognosis in various cancers. The review also explores TF's role in promoting cancer cell metastasis, angiogenesis, and venous thromboembolism (VTE)...

INTRODUCTION: Gaoyou duck is famous in China and abroad for its good production of double-yolk eggs. However, there has been no systematic research on the egg-laying characteristics of the Gaoyou duck, which limits the development and utilization of breed resource. METHODS: To identify the essential genes related to ovarian development, the transcriptome profiles of the ovaries of Gaoyou ducks at different physiological stages were analyzed. The transcriptome profiles of the ovaries of Gaoyou ducks at 150 d (before laying), 240 d (egg laying) and 500 d (nesting) were constructed, and the differentially expressed genes (DEGs) underwent GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses...

Endometriosis is a common gynecological disorder that causes female infertility. Our recent research found that excessive oxidative stress in ovaries of endometriosis patients induced senescence of cumulus granulosa cells. Here, we analyzed the transcriptomic and metabolomics profiles of follicles in a mouse model of endometriosis and in patients with endometriosis and investigated the potential function of changed metabolites in granulosa cells. RNA-sequencing indicated that both endometriosis lesions and oxidative stress in mice induced abnormalities of reactive oxidative stress, steroid hormone biosynthesis, and lipid metabolism...

Platinum resistance is a major obstacle to the treatment of ovarian cancer and is correlated with poor clinical outcomes. Intratumor heterogeneity plays a key role in chemoresistance. Recent studies have emphasized the contributions of genetic and epigenetic factors to the development of intratumor heterogeneity. Although the clinical significance of multisubunit chromatin remodeler, switch/sucrose nonfermenting (SWI/SNF) complexes in cancers has been reported, the impacts of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4/subfamily A, member 2 (SMARCA4/A2) expression patterns in human cancer tissues have not been fully elucidated...

Ovulation rate and litter size are the main reproductive traits with high economic value in the sheep breeding industry. In this study, three Shal ewes (multiparous) and three Sangsari ewes (uniparous) at the age of 5 were used. The live weight was between 45 and 50 kg at extremely body condition score of 3. These breeds are marked seasonal reproduction activity and are often bred in semi-closed breeding system. Total RNAs were extracted from the ovarian tissues and RNA sequencing was carried out. The DAVID (Database for Annotation, Visualization and Integrated Discovery) database was then used to annotate genes, and the string database and the cytoscape software were used to investigate their interactions...

ETHNOPHARMACOLOGICAL RELEVANCE: Huanglian-Houpo Decoction (HLHP), a classical prescription, has been used to treat gastrointestinal diseases for hundreds of years in TCM. However, the effective constituents and underlying mechanisms of HLHP in the treatment of ulcerative colitis (UC) have not been fully investigated. AIM OF THE STUDY: This study aimed to reveal the potential anti-UC mechanisms of 50% ethanol extraction of HL and HP (EHLHP), combining transcriptomes and network pharmacology, as well as the animal experiment verification...

To determine whether sevoflurane postconditioning protects against cerebral ischemia reperfusion (I/R) injury and its potential mechanism, we employed bioinformatic analysis, neurological assessments, and western blot analysis, as well as triphenyl tetrazolium chloride, hematoxylin and eosin, Nissl, and immunofluorescence staining. We identified 103 differentially expressed genes induced by cerebral I/R, including 75 upregulated genes and 28 downregulated genes enriched for certain biological processes (involving regulation of inflammatory responses, cellular responses to interleukin 1, and chemokine activity) and signaling pathways (such as transcriptional misregulation in cancer, interleukin-17 signaling, rheumatoid arthritis, MAPK signaling, and Toll-like receptor signaling)...

Squamous cell carcinomas are triggered by marked elevation of RAS-MAPK signalling and progression from benign papilloma to invasive malignancy1-4 . At tumour-stromal interfaces, a subset of tumour-initiating progenitors, the cancer stem cells, obtain increased resistance to chemotherapy and immunotherapy along this pathway5,6 . The distribution and changes in cancer stem cells during progression from a benign state to invasive squamous cell carcinoma remain unclear. Here we show in mice that, after oncogenic RAS activation, cancer stem cells rewire their gene expression program and trigger self-propelling, aberrant signalling crosstalk with their tissue microenvironment that drives their malignant progression...

Despite the well-known hepatoprotective role of the epidermal growth factor receptor (EGFR) pathway upon acute damage, its specific actions during chronic liver disease, particularly cholestatic injury, remain ambiguous and unresolved. Here, we analyzed the consequences of inactivating EGFR signaling in the liver on the regenerative response following cholestatic injury. For that, transgenic mice overexpressing a dominant negative mutant human EGFR lacking tyrosine kinase activity (ΔEGFR) in albumin-positive cells were submitted to liver damage induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), an experimental model resembling human primary sclerosing cholangitis...

Many primary-tumor subregions exhibit low levels of molecular oxygen and restricted access to nutrients due to poor vascularization in the tissue, phenomenon known as hypoxia. Hypoxic tumors are able to regulate the expression of certain genes and signaling molecules in the microenvironment that shift it towards a more aggressive phenotype. The transcriptional landscape of the tumor favors malignant transformation of neighboring cells and their migration to distant sites. Herein, we focused on identifying key proteins that participate in the signaling crossroads between hypoxic environment and metastasis progression that remain poorly defined...