The therapeutic effect and underlying biochemical mechanism of methylprednisolone and D-methionine in "rescuing" noise-induced hearing loss in guinea pigs.

Objectives: Currently, there are no approved therapeutics for noise-induced hearing loss (NIHL). Both oxidative stress and cochlear inflammation play important roles in the mechanism of NIHL. In this study, we evaluate the effect of D-methionine (D-met) and methylprednisolone (MP) on noise-induced hearing loss of guinea pigs.

The Role of SMAD7 in the Epigenetic Regulation of TGF-β Targets in the Metastasis of Ovarian Cancer.

The role of TGF-β signaling in the epigenetic modifications involved in ovarian cancer is not fully understood. This study investigated the relationship between TGF-β signaling, epigenetic modifications, and cellular behaviors in ovarian cancer. We found that E-cadherin, a key cell adhesion molecule, underwent epigenetic silencing via promoter DNA hypermethylation in ovarian cancer cell lines and that this was accompanied by the upregulation of vimentin, which is indicative of a mesenchymal and invasive phenotype.

Nanoarchitectonics with cetrimonium bromide on metal nanoparticles for linker-free detection of toxic metal ions and catalytic degradation of 4-nitrophenol.

Heavy metal ions and organic pollutants, such as 4-nitrophenol (4-NP), pose significant environmental and human health threats. Addressing these challenges necessitates using advanced nanoparticle-based systems capable of efficient detection and degradation. However, conventional approaches utilizing strong capping agents like cetrimonium bromide (CTAB) on nanoparticles lead to limitations due to the rigid nature of CTAB.

LY-2183240 enhances reward-seeking behavior with inducing neuronal excitation and early apoptosis in mouse.

Cannabinoids interact with cannabinoid receptors, influencing diverse central nervous system (CNS) and peripheral functions, including anxiety, depression, and cognition. CB1 and CB2 receptors modulate signaling cascades via G-protein coupling, with anandamide acting as an endogenous ligand for CB1 receptors. LY-2183240, a putative endocannabinoid transport blocker, elevates brain anandamide levels, showing therapeutic potential in pain management and alcohol-related behaviors.

Copper oxide nanoparticles exacerbate chronic obstructive pulmonary disease by activating the TXNIP-NLRP3 signaling pathway.

Background: Although copper oxide nanoparticles (CuONPs) offer certain benefits to humans, they can be toxic to organs and exacerbate underlying diseases upon exposure. Chronic obstructive pulmonary disease (COPD), induced by smoking, can worsen with exposure to various harmful particles. However, the specific impact of CuONPs on COPD and the underlying mechanisms remain unknown.

TXNIP regulates pulmonary inflammation induced by Asian sand dust.

Asian sand dust (ASD), a seasonal dust storm originating from the deserts of China and Mongolia, affects Korea and Japan during the spring, carrying soil particles and a variety of biochemical components. Exposure to ASD has been associated with the onset and exacerbation of respiratory disorders, although the underlying mechanisms remain unclear. This study investigates ASD-induced pulmonary toxicity and its mechanistic pathways, focusing on the role of thioredoxin-interacting protein (TXNIP).

Improving the construction and prediction strategy of the Air Quality Health Index (AQHI) using machine learning: A case study in Guangzhou, China.

Effectively capturing the risk of air pollution and informing residents is vital to public health. The widely used Air Quality Index (AQI) has been criticized for failing to accurately represent the non-threshold linear relationship between air pollution and health outcomes. Although the Air Quality Health Index (AQHI) was developed to address these limitations, it lacks comprehensive construction criteria.

Comprehensive analysis of adverse outcome pathway, potency, human exposure supports carcinogenicity of polyhexamethylene guanidine phosphate in lung cancer.

In this study, we investigated the potential mechanisms by which polyhexamethylene guanidine phosphate (PHMG-p), a known respiratory irritant, may contribute to lung cancer development. Using the adverse outcome pathway (AOP) framework, we analyzed established databases (such as AOP-Wiki) and employed AI tools (AOP-helpFinder) to identify key events (KEs) associated with lung carcinogenesis. Our analysis indicates that chronic inhalation of PHMG-p triggers a non-genotoxic pathway, characterized by cell membrane disruption, inflammation, and oxidative stress, with a point of departure (POD) of 0.

Double Heterozygous Pathogenic Variants in and in Boy with Undifferentiated Embryonal Sarcoma of the Liver.

Undifferentiated embryonal sarcoma of the liver is a rare mesenchymal malignancy that predominantly occurs in children. The relationship between this tumor entity and germline pathogenic variants (PVs) remains undefined. Here, we present the clinical case of a male patient diagnosed with undifferentiated embryonal sarcoma of the liver.

L-DOPA Promotes Functional Proliferation Through GPR143, Specific L-DOPA Receptor of Astrocytes.

l-3,4-Dihydroxyphenylalanine (levodopa and L-DOPA in this text), alongside dopamine, boasts high biocompatibility, prompting industrial demand for its use as a coating material. Indeed, the effectiveness of L-DOPA is steadily rising as it serves as an oral therapeutic agent for neurodegenerative brain diseases, particularly Parkinson's disease (PD). However, the effects of L-DOPA on the growth and function of astrocytes, the main glial cells, and the most numerous glial cells in the brain, are unknown.

From historical drugs to present perils: UHPLC-QqQ-MS/MS determination of methaqualone and its designer analogs (NPS) with comprehensive fragmentation pathways study (QTOF).

Methaqualone, introduced in the 1960s as a sedative-hypnotic alternative to barbiturates, was withdrawn from the market due to its side effects and growing recreational use. Despite this, interest in methaqualone and its analogs remains high, raising concerns about potential abuse in the future. An ultra-high-performance liquid chromatography method coupled with triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS) was developed to determine nine methaqualone-related compounds simultaneously.

Microbiome divergence across four major Indian riverine water ecosystems impacted by anthropogenic contamination: A comparative metagenomic analysis.

Rivers are critical ecosystems that support biodiversity and local livelihoods. This study aimed to evaluate the effects of metal contamination and anthropogenic activities on microbial and phage community dynamics within major Indian river ecosystems, focusing on the Ganga, Narmada, Cauvery, and Gomti rivers -using metagenomic techniques, Biolog, and ICP-MS analysis. Significant variations in microbial communities were observed both within each river and across the four systems, influenced by ecological factors like geography and hydrology, as well as anthropogenic pressures.

Xianling Lianxia formula improves the efficacy of trastuzumab by enhancing NK cell-mediated ADCC in HER2-positive BC.

Trastuzumab has improved survival rates in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), but drug resistance leads to treatment failure. Natural killer (NK) cell-mediated antibody-dependent cell cytotoxicity (ADCC) represents an essential antitumor immune mechanism of trastuzumab. Traditional Chinese medicine (TCM) has been used for centuries to treat diseases because of its capacity to improve immune responses.

Endoplasmic reticulum stress induced autophagy in cancer and its potential interactions with apoptosis and ferroptosis.

The endoplasmic reticulum (ER) is a dynamic organelle that is a site of the synthesis of proteins and lipids, contributing to the regulation of proteostasis, lipid metabolism, redox balance, and calcium storage/-dependent signaling events. The disruption of ER homeostasis due to the accumulation of misfolded proteins in the ER causes ER stress which activates the unfolded protein response (UPR) system through the activation of IRE1, PERK, and ATF6. Activation of UPR is observed in various cancers and therefore, its association with process of carcinogenesis has been of importance.

Amplified response of drug-induced liver fibrosis immune cell co-culture in a 3D hepatic fibrosis model.

Liver fibrosis, a critical consequence of chronic liver diseases, is characterized by excessive extracellular matrix (ECM) deposition driven by inflammation. This process involves complex interactions among hepatocytes, hepatic stellate cells (HSCs), and Kupffer cells, the liver's resident macrophages. Kupffer cells are essential in initiating fibrosis through the release of pro-inflammatory cytokines that activate HSCs.

Transport of Golgi-localized β-catenin p-S47 by KIF11 or KIFC3 induces primary ciliogenesis.

Primary cilium is an important hub for cell signaling and dysregulation of primary cilia assembly and disassembly is associated with the development of cancer and chemotherapeutic drug resistance, as well as the genetic disorders collectively known as ciliopathy. β-catenin plays a major role in canonical Wnt signaling; however, its association with primary cilia has only recently been highlighted in reports of β-catenin-mediated primary ciliogenesis. In this study, we found that β-catenin p-S47 was localized to the Golgi apparatus and the nucleus, and the amount of β-catenin p-S47 at these locations was significantly higher during primary ciliogenesis compared with asynchronous cell growth conditions.

Decisive role of mDia-family formins in cell cortex function of highly adherent cells.

Cortical formins, pivotal for the assembly of linear actin filaments beneath the membrane, exert only minor effects on unconfined cell migration of weakly and moderately adherent cells. However, their impact on migration and mechanostability of highly adherent cells remains poorly understood. Here, we demonstrate that loss of cortical actin filaments generated by the formins mDia1 and mDia3 drastically compromises cell migration and mechanics in highly adherent fibroblasts.

Wnt signaling in the tumor microenvironment: A driver of brain tumor dynamics.

The Wnt signaling pathway is important for cell growth and development in the central nervous system and its associated vasculature. Thus, it is an interesting factor for establishing anti-brain cancer therapy. However, simply inhibiting the Wnt signaling pathway in patients with brain tumors is not an effective anti-cancer therapy.