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Integrated Multi-Omic Analysis Reveals KDM5B as a Regulator of Microglial Reactivity to Immunomodulatory Stimuli.

Microglia maintain brain homeostasis through coordinated pathways, including cell migration, phagocytosis, and secretion of immune-related signaling factors. Microglial reactivity is associated with a variety of functional outcomes that are highly context-dependent withepigenetic regulation through DNA methylation and histone modifications implicated in this complex control of microglial plasticity. Specifically, in relation to histone methylation, lysine-specific demethylase 5B (KDM5B) has been associated with several pathophysiological states, including neurodevelopmental and inflammatory di

From State, Pathway, to Niche: The Ternary Network of Breast Cancer Stem-like Cells Driving Tumor Progression and Combination Therapy Prospects.

Breast cancer stem-like cells (bCSCs) fundamentally represent a highly dynamic "immune-adaptive functional state" rather than a fixed cellular lineage, serving as the core engine driving tumor recurrence, metastasis, and therapeutic resistance. Despite rapid advances, the heterogeneity of bCSC states and their intricate interactions with the immune microenvironment lack systematic integration. This review centers on the dynamic evolution and niche adaptation of bCSCs. First, we systematically dissect the multilayered regulatory network maintaining stemness, encompassing core transcription fact

Network Pharmacology and Molecular Docking Reveals Mechanism of Camphor on Liver Toxicity in Zebrafish.

OBJECTIVE: This study aimed to investigate the hepatotoxicity of camphor on zebrafish and its mechanism of toxicity. METHODS: We calculated concentration-response curves for zebrafish larvae treated with camphor at 72-h postexposure (hpe) and observed its toxic effects on liver. Employing network pharmacology and molecular pairs to predict key targets of camphor-induced hepatotoxicity, these critical targets were subsequently validated via qPCR. RESULTS: This study indicates that following 72 hpe to camphor, the LC50 and LC10 values for zebrafish larvae were 336 and 300 μg/mL, respectively.

Transcutaneous auricular vagus nerve stimulation and stress regulation: preclinical insights and unresolved challenges.

Chronic stress exposure contributes to the onset and maintenance of a wide range of mental and physical disorders. Non-invasive modulation of vagal pathways has received increasing attention as a potential strategy for the prevention and treatment of stress-related conditions, given the central role of the vagus nerve in brain-body communication. By stimulating auricular vagal afferents, transcutaneous auricular vagal nerve stimulation (taVNS) is proposed to engage stress regulatory circuits, with downstream effects that may modulate stress-related physiology. Consistent with this mechanistic

Pyroptosis-immune cell cross talk in asthma: From molecular mechanisms to precision therapeutics.

Asthma is a heterogeneous chronic airway disease characterized by complex inflammation. Pyroptosis, a pro-inflammatory form of programmed cell death mediated by gasdermin (GSDM) family proteins, has recently emerged as a critical amplifier of airway inflammation and tissue remodeling in asthma. This review delineates the molecular underpinnings of pyroptosis, focusing on the roles of canonical (e.g., NLRP3-caspase-1) and non-canonical (e.g., caspase-4/5/11) inflammasome pathways, as well as the broader concept of PANoptosis. We elaborate on how the pore-forming activity of GSDMD and other GSDM

Embryonic Benzo[a]pyrene Exposure Induces Multigenerational Reproductive Effects on Adult Male Medaka: Phenotypic and Transcriptomic Insights.

Benzo[a]pyrene (B[a]P), a ubiquitous environmental pollutant, poses a significant threat to male reproductive health, but the underlying latent molecular mechanisms remain virtually unknown. This study investigated the effects of embryonic B[a]P exposure on testicular function and spermatogenesis in F0 and F1 adult male medaka (Oryzias latipes). Embryos were exposed to sublethal concentrations (2.5, 20, and 80 μg/L) for 8 days and then raised in clean water until they reached adulthood. Transcriptomic analysis of F0 testicular tissues revealed widespread dysregulation of critical pathways. Exp…

Repurposing of nervous system drugs for cancer treatment: recent advances, challenges, and future perspectives.

The nervous system plays a critical role in developmental biology and oncology, influencing processes from ontogeny to the complex dynamics of cancer progression. Interactions between the nervous system and cancer significantly affect oncogenesis, tumor growth, invasion, metastasis, treatment resistance, inflammation that promotes tumors, and the immune response. A comprehensive understanding of the signal transduction pathways involved in cancer biology is essential for devising effective anti-cancer strategies and overcoming resistance to existing therapies. Recent advances in cancer neurosc

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… The interplay extends to the modulation of critical pathways such as TGF-β, which serves a dual role in cancer by acting as a tumor suppressor in early stages while promoting progression in later stages [ 25 ]. … Furthermore, certain antipsychotics have been investigated for their potential to affect the CTLA-4 immune checkpoint, another critical pathway that cancer cells exploit to evade immune detection. …

Targeting Prostate Cancer Metabolism Through Transcriptional and Epigenetic Modulation: A Multi-Target Approach to Therapeutic Innovation.

Prostate cancer (PCa) therapy faces challenges due to tumor heterogeneity, plasticity, and progression. Metabolic reprogramming, a dynamic process, has emerged as a key focus in PCa treatment. However, conventional therapies targeting cancer-specific metabolic pathways or employing chemosensitizers are often limited by compensatory mechanisms and metabolic complexity. This review highlights the roles of transcription factors, including AR, p53, c-Myc, HIF-1, Nrf2, and PPARγ, in regulating PCa metabolism by influencing signaling pathways, enzymes, and gene expression. Multi-target compounds, pa

The golden touch: a comprehensive network pharmacology-guided review of synergy between curcumin and PARP inhibitors.

Cancer remains the second leading cause of death globally. Poly (ADP-ribose) polymerase inhibitors (PARPi) are effective targeted therapies, but their use is largely limited to BRCA-deficient cancers and is often hampered by resistance. This review explores combining PARPi with curcumin, a natural polyphenol, as an adjunct therapy. We reviewed literature and employed a network pharmacology approach to investigate shared molecular mechanisms. Curcumin induces DNA double-strand breaks while simultaneously impairing multiple repair pathways, including homologous recombination and non-homologous e

Combination therapies and other therapeutic approaches targeting the NLRP3 inflammasome and neuroinflammatory pathways: a promising approach for traumatic brain injury.

OBJECTIVES: Traumatic brain injury (TBI) precipitates a neuroinflammatory cascade, with the NLRP3 inflammasome emerging as a critical mediator. This review scrutinizes the complex activation pathways of the NLRP3 inflammasome by underscoring the intricate interplay between calcium signaling, mitochondrial disturbances, redox imbalances, lysosomal integrity, and autophagy. It is hypothesized that a combination therapy approach-integrating NF-κB pathway inhibitors with NLRP3 inflammasome antagonists-holds the potential to synergistically dampen the inflammatory storm associated with TBI. METHOD

Unraveling the Inactivation Mechanisms of Human Adenovirus 2 in Sunlight Disinfection: Synergism between Direct and Indirect Pathways.

Adenovirus (HAdV), a double-stranded DNA virus, exhibits resistance to direct inactivation by UVC and solar UVB radiation in water, owing to its ability to repair UV-induced genome damage using host cellular machinery. In the presence of dissolved organic matter (DOM), however, previous studies have reported unexpectedly rapid sunlight-mediated inactivation, even after accounting for indirect effects mediated by photochemically produced reactive intermediates (PPRIs). Here, we hypothesized that a synergistic interaction between direct and indirect inactivation pathways compromises HAdV2's geno

Revealing the association between East Asian oral microbiome and colorectal cancer through Mendelian randomization and multi-omics analysis.

BACKGROUND: Colorectal cancer (CRC) poses a global health threat, with the oral microbiome increasingly implicated in its pathogenesis. This study leverages Mendelian Randomization (MR) to explore causal links between oral microbiota and CRC using data from the China National GeneBank and Biobank Japan. By integrating multi-omics approaches, we aim to uncover mechanisms by which the microbiome influences cellular metabolism and cancer development. METHODS: We analyzed microbiome profiles from 2017 tongue and 1915 saliva samples, and GWAS data for 6692 CRC cases and 27178 controls. Significant

MicroRNA copy number alterations in the malignant transformation of pleomorphic adenoma to carcinoma ex pleomorphic adenoma.

OBJECTIVE: This study used array comparative genomic hybridization to assess copy number alterations (CNAs) involving miRNA genes in pleomorphic adenoma (PA), recurrent pleomorphic adenoma (RPA), residual PA, and carcinoma ex pleomorphic adenoma (CXPA). MATERIALS AND METHODS: We analyzed 13 PA, 4 RPA, 29 CXPA, and 14 residual PA using Nexus Copy Number Discovery software. The miRNAs genes affected by CNAs were evaluated based on their expression patterns and subjected to pathway enrichment analysis. RESULTS: Across the groups, we found 216 CNAs affecting 2261 miRNA genes, with 117 in PA, 59

Canonical and Non-Canonical Wnt Signaling Generates Molecular and Cellular Asymmetries to Establish Embryonic Axes.

The formation of embryonic axes is a critical step during animal development, which contributes to establishing the basic body plan in each particular organism. Wnt signaling pathways play pivotal roles in this fundamental process. Canonical Wnt signaling that is dependent on β-catenin regulates the patterning of dorsoventral, anteroposterior, and left-right axes. Non-canonical Wnt signaling that is independent of β-catenin modulates cytoskeletal organization to coordinate cell polarity changes and asymmetric cell movements. It is now well documented that components of these Wnt pathways bioch

Single-cell RNA sequencing identifies interferon-inducible monocytes/macrophages as a cellular target for mitigating the progression of abdominal aortic aneurysm and rupture risk.

AIMS: Abdominal aortic aneurysm (AAA) represents a life-threatening condition characterized by medial layer degeneration of the abdominal aorta. Nevertheless, knowledge regarding changes in regulators associated with aortic status remains incomplete. A thorough understanding of cell types and signalling pathways involved in the development and progression of AAAs is essential for the development of medical therapy. METHODS AND RESULTS: We harvested specimens of the abdominal aorta with different pathological features in Angiotensin II (AngII)-infused ApoE-/- mice, conducted scRNA-seq, and ide

Therapeutic potential of hydrogen sulfide in osteoarthritis development.

The pathological mechanisms and treatments of osteoarthritis (OA) are critical topics in medical research. This paper reviews the regulatory mechanisms of hydrogen sulfide (H2S) in OA and the therapeutic potential of H2S donors. The review highlights the importance of changes in the endogenous H2S pathway in OA development and systematically elaborates on the role of H2S as a third gaseous transmitter that regulates inflammation, oxidative stress, and pain associated with OA. It also explains how H2S can lessen bone and joint inflammation by inhibiting leukocyte adhesion and migration, reducin

Vascular remodelling in cardiovascular diseases: hypertension, oxidation, and inflammation.

Optimal vascular structure and function are essential for maintaining the physiological functions of the cardiovascular system. Vascular remodelling involves changes in vessel structure, including its size, shape, cellular and molecular composition. These changes result from multiple risk factors and may be compensatory adaptations to sustain blood vessel function. They occur in diverse cardiovascular pathologies, from hypertension to heart failure and atherosclerosis. Dynamic changes in the endothelium, fibroblasts, smooth muscle cells, pericytes or other vascular wall cells underlie remodell

The dynamic molecular characteristics of neutrophils are associated with disease progression in dengue patients.

Dengue, the most prevalent mosquito-borne disease worldwide, poses a significant health burden. This study integrates clinical data and transcriptomic datasets from different phases of dengue to investigate distinctive and shared cellular and molecular features. Clinical data from 29 dengue patients were collected and analyzed alongside a public transcriptomic data set (GSE28405) to perform differential gene expression analysis, functional enrichment, immune landscape assessment, and development of machine learning model. Neutropenia was observed in 54.79% of dengue patients, particularly duri

Simultaneous Inhibition of Thrombosis and Inflammation Is Beneficial in Treating Acute Myocardial Infarction.

Myocardial ischemia reperfusion injury (IRI) in acute coronary syndromes is a condition in which ischemic/hypoxic injury to cells subtended by the occluded vessel continues despite successful resolution of the thrombotic obstruction. For decades, most efforts to attenuate IRI have focused on interdicting singular molecular targets or pathways, but none have successfully transitioned to clinical use. In this work, we investigate a nanoparticle-based therapeutic strategy for profound but local thrombin inhibition that may simultaneously mitigate both thrombosis and inflammatory signaling pathway

Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System.

It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning is the knowledge that metabolic disease is intimately tied to neurodegenerative disorders, affecting both the central and peripheral nervous systems as well as leading to dementia, the seventh leading cause of death. New and innovative therapeutic strategies that address cellular metabolism, apoptosis, autophagy, and pyroptosis, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), growth fact