Post-translational modifications in DNA damage repair: mechanisms underlying temozolomide resistance in glioblastoma.

Temozolomide (TMZ) resistance is one of the critical factors contributing to the poor prognosis of glioblastoma (GBM). As a first-line chemotherapeutic agent for GBM, TMZ exerts its cytotoxic effects through DNA alkylation. However, its therapeutic efficacy is significantly compromised by enhanced DNA damage repair (DDR) mechanisms in GBM cells.

Auditory processing deficits in autism spectrum disorder: mechanisms, animal models, and therapeutic directions.

Auditory processing abnormalities are a prominent feature of Autism Spectrum Disorder (ASD), significantly affecting sensory integration, communication, and social interaction. This review delves into the neurobiological mechanisms underlying these deficits, including structural and functional disruptions in the auditory cortex, imbalances in excitatory and inhibitory signaling, and synaptic dysfunction. Genetic contributions from mutations in CNTNAP2, SHANK3, FMR1, and FOXP2 are explored, highlighting their roles in auditory abnormalities.

Intervening Non-Small-Cell Lung Cancer Progression by Cell Membrane Coated Platycodin D via Regulating Hsa-miR-1246/FUT9/GSK3β Pathway.

Purpose: Metastatic non-small cell lung cancer (NSCLC) remains a global health threat, with patients facing inevitable disease progression despite standard-of-care therapy. Prior studies showed Platycodin D (PD)-induced cell cycle arrest and apoptosis in NSCLC via RNA regulatory network, yet elucidating PD's mechanisms in NSCLC progression is challenging in the real world.

Methods: Biological effects of PD on NSCLC cell lines A549 and PC-9 were assessed through in vitro assays, encompassing apoptosis, proliferation, colony formation, migration and invasion.

The transcription factor CREB regulates epithelial-mesenchymal transition of lens epithelial cells by phosphorylation-dependent and phosphorylation-independent mechanisms.

Epithelial mesenchymal transition (EMT) of lens epithelial cells (LECs) is one of the most important pathogenic mechanisms in lens fibrotic disorders, and the regulatory mechanisms of EMT have not been fully understood. Here, we demonstrate that the cAMP-response element binding protein (CREB) can regulate lens EMT in a phosphorylation-dependent and phosphorylation-independent manners with dual mechanisms. First, CREB-S133 phosphorylation is implicated in TGFβ-induced EMT of mouse LECs and also in injury-induced mouse anterior subcapsular cataract model.

Dysregulation of parvalbumin expression and neurotransmitter imbalance in the auditory cortex of the BTBR mouse model of autism spectrum disorder.

Individuals diagnosed with autism spectrum disorder (ASD) frequently exhibit abnormalities in auditory perception, a phenomenon potentially attributed to alterations in the excitatory and inhibitory cells constituting cortical circuits. However, the exact genetic factors and cell types affected by ASD remain unclear. The present study investigated the balance of excitatory and inhibitory activity in the auditory cortex using BTBR T Itpr3/J (BTBR) mice, a well-established model for autism research.

Intestinal microbiota imbalance resulted by anti-Toxoplasma gondii immune responses aggravate gut and brain injury.

Background: Toxoplasma gondii infection affects a significant portion of the global population, leading to severe toxoplasmosis and, in immunocompromised patients, even death. During T. gondii infection, disruption of gut microbiota further exacerbates the damage to intestinal and brain barriers.

Efficacy and safety of traditional Chinese medicine decoction as an adjuvant treatment for diabetic nephropathy: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to assess the efficacy and safety of traditional Chinese medicine decoction as an adjunctive treatment for diabetic nephropathy in systematic evaluations. A comprehensive search was conducted in PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases, covering the period from January 2013 to July 2023. The search was restricted to randomized controlled trials (RCTs) conducted within the past decade that investigated the use of TCM decoction as an adjunctive treatment for diabetic nephropathy.

Toxoplasma gondii infection positively associated with schizophrenia: Evidences from UK Biobank cohort and case-controlled studies.

Toxoplasma gondii (T. gondii) is an opportunistic pathogen affecting about 1/3 of world population. While often asymptomatic in immunocompetent individuals, it can lead to severe toxoplasmosis in immunocompromised patients.

Population-based cohort study of Toxoplasma gondii P22 antibody positivity correlation with anxiety.

Background: Accumulating evidence suggests that latent infection with Toxoplasma gondii (T. gondii) is associated with a variety of neuropsychiatric and behavioral conditions. This research aims to explore the potential correlation between T.

Opening the Black Box: Spatial Transcriptomics and the Relevance of Artificial Intelligence-Detected Prognostic Regions in High-Grade Serous Carcinoma.

Image-based deep learning models are used to extract new information from standard hematoxylin and eosin pathology slides; however, biological interpretation of the features detected by artificial intelligence (AI) remains a challenge. High-grade serous carcinoma of the ovary (HGSC) is characterized by aggressive behavior and chemotherapy resistance, but also exhibits striking variability in outcome. Our understanding of this disease is limited, partly due to considerable tumor heterogeneity.

Platycodin D inhibits angiogenic vascular mimicry in NSCLC by regulating the eIF4E-mediated RNA methylome.

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Tracing back primed resistance in cancer via sister cells.

Exploring non-genetic evolution of cell states during cancer treatments has become attainable by recent advances in lineage-tracing methods. However, transcriptional changes that drive cells into resistant fates may be subtle, necessitating high resolution analysis. Here, we present ReSisTrace that uses shared transcriptomic features of sister cells to predict the states priming treatment resistance.

SUMO1-regulated DBC1 promotes p53-dependent stress-induced apoptosis of lens epithelial cells.

Deleted in breast cancer 1 (DBC1) was initially identified from a homozygously deleted region in human chromosome 8p21. It has been well established that DBC1 plays a dual role during cancer development. Depending on the physiological context, it can promote or inhibit tumorigenesis.

HSP90β prevents aging-related cataract formation through regulation of the charged multivesicular body protein (CHMP4B) and p53.

Cataract is a leading ocular disease causing global blindness. The mechanism of cataractogenesis has not been well defined. Here, we demonstrate that the heat shock protein 90β (HSP90β) plays a fundamental role in suppressing cataractogenesis.

Endothelial TIE1 Restricts Angiogenic Sprouting to Coordinate Vein Assembly in Synergy With Its Homologue TIE2.

Background: Vascular growth followed by vessel specification is crucial for the establishment of a hierarchical blood vascular network. We have shown that TIE2 is required for vein development while little is known about its homologue TIE1 (tyrosine kinase with immunoglobulin-like and EGF [epithelial growth factor]-like domains 1) in this process.

Methods: We analyzed functions of TIE1 as well as its synergy with TIE2 in the regulation of vein formation by employing genetic mouse models targeting , , and , together with in vitro cultured endothelial cells to decipher the underlying mechanism.

The effect of Chinese herbal formulas combined with metformin on modulating the gut microbiota in the amelioration of type 2 diabetes mellitus: A systematic review and meta-analysis.

Unlabelled: To assess and analyse the effectiveness and safety of combined Chinese herbal formula (CHF) and metformin treatment in the modulation of the gut microbiota in the amelioration of type 2 diabetes mellitus(T2DM), all publications addressing the effect of this combination treatment on the quantitative alterations in the gut microbiota and glucose parameters were collected. Rob tool in the Cochrane handbook was performed to evaluate the methodological quality of all included studies. Relevant information and statistics were abstracted and synthesized in Review Manager 5.

Whole Transcriptome Analysis Identifies Platycodin D-Mediated RNA Regulatory Network in Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) is one of the most fatal malignant tumors harmful to human health. Previous studies report that (PD) exhibits anti-tumor effects in multiple human cancers, including NSCLC, but the underlying mechanisms are largely unknown. Accumulating evidence indicates that non-coding RNAs (ncRNAs) participate in NSCLC disease progression, but the link between PD and the ncRNAs in NSCLC is poorly elucidated.

Hybrid F-florbetapir PET/MRI for assessing myelin recovery in GFAP-A patients.

Glial fibrillary acidic protein astrocytopathy (GFAP-A) is a rare autoimmune disease of the central nervous system that was newly reported in 2016. Previous studies have speculated that the pathological mechanism and clinical outcome of GFAP-A lie in the demyelination of the central nervous system, but due to the limitations of MR, this conclusion has not been further confirmed from the perspective of neuroimaging. A non-invasive, quantitative measurement of demyelination would be clinically valuable, given its critical role in mediating GFAP-A.

Bipartite network models to design combination therapies in acute myeloid leukaemia.

Combination therapy is preferred over single-targeted monotherapies for cancer treatment due to its efficiency and safety. However, identifying effective drug combinations costs time and resources. We propose a method for identifying potential drug combinations by bipartite network modelling of patient-related drug response data, specifically the Beat AML dataset.

Antitumoral Effect of Plocabulin in High Grade Serous Ovarian Carcinoma Cell Line Models.

Ovarian cancer (OC) is a life-threatening tumor and the deadliest among gynecological cancers in developed countries. First line treatment with a carboplatin/paclitaxel regime is initially effective in the majority of patients, but most advanced OC will recur and develop drug resistance. Therefore, the identification of alternative therapies is needed.

MYPT1/PP1-Mediated EZH2 Dephosphorylation at S21 Promotes Epithelial-Mesenchymal Transition in Fibrosis through Control of Multiple Families of Genes.

The methyltransferase EZH2 plays an important role in regulating chromatin conformation and gene transcription. Phosphorylation of EZH2 at S21 by AKT kinase suppresses its function. However, protein phosphatases responsible for the dephosphorylation of EZH2-S21 remain elusive.

The effect of secondhand smoke exposure on self-satisfaction and perceived freedom of life choice.

The present study aims to examine whether secondhand smoke exposure (SHSE) in university students can affect three indices of self-satisfaction related to depression as indiced by appearance, weight, and freedom of life choice. We collected data from 740 nonsmoking students in the summer of 2018, of which 57.84% were exposed to secondhand smoke.

A community challenge for a pancancer drug mechanism of action inference from perturbational profile data.

The Columbia Cancer Target Discovery and Development (CTD2) Center is developing PANACEA, a resource comprising dose-responses and RNA sequencing (RNA-seq) profiles of 25 cell lines perturbed with ∼400 clinical oncology drugs, to study a tumor-specific drug mechanism of action. Here, this resource serves as the basis for a DREAM Challenge assessing the accuracy and sensitivity of computational algorithms for drug polypharmacology predictions. Dose-response and perturbational profiles for 32 kinase inhibitors are provided to 21 teams who are blind to the identity of the compounds.

SynergyFinder Plus: Toward Better Interpretation and Annotation of Drug Combination Screening Datasets.

Combinatorial therapies have been recently proposed to improve the efficacy of anticancer treatment. The SynergyFinder R package is a software used to analyze pre-clinical drug combination datasets. Here, we report the major updates to the SynergyFinder R package for improved interpretation and annotation of drug combination screening results.

FoxP3 Tr1 Cell in Generalized Myasthenia Gravis and Its Relationship With the Anti-AChR Antibody and Immunomodulatory Cytokines.

The changes in the number and function of regulatory T cells (Tregs) are thought to play important roles in the pathogenesis of generalized myasthenia gravis (gMG). Previous studies have suggested the decrease of FoxP3 Treg cells in the MG development. However, there is no study on the pathophysiological mechanism of FoxP3Treg, especially Tr1 cells, in gMG patients.