Colemanite Attenuates Metaflumizone-Mediated Hematic/Hepatic Inflammation and DNA Damage in Oncorhynchus mykiss.

This study was arranged to assign the LC value and effects of metaflumizone (MFZ) in Oncorhynchus mykiss blood/liver tissue with a multibiomarker approach. In addition, the positive/negative responses of the colemanite (COL) substance for integrating therapeutic agents into aquaculture were also discussed. Hematology profile revealed that red blood cell (RBC), hemoglobin (Hgb), and hematocrit (Hct) decreased temporally as a result of MFZ application compared to the control group.

Longitudinal big biological data in the AI era.

Generating longitudinal and multi-layered big biological data is crucial for effectively implementing artificial intelligence (AI) and systems biology approaches in characterising whole-body biological functions in health and complex disease states. Big biological data consists of multi-omics, clinical, wearable device, and imaging data, and information on diet, drugs, toxins, and other environmental factors. Given the significant advancements in omics technologies, human metabologenomics, and computational capabilities, several multi-omics studies are underway.

Anticancer effects and mechanisms of , and on human lung carcinoma and hepatoma cells.

Herbs are extensively utilized in Traditional Chinese Medicine (TCM) for lung and liver cancer treatment, but the mechanisms behind these herbs remain largely unknown. Here, high-throughput transcriptomic analysis technology was used to uncover molecular mechanisms of herbal treatment. Furthermore, we developed a compound recognition approach utilizing the LINCS L1000 database to identify potential treatment targets.

New Gene Targets for Diagnosis and Therapy of Diabetic Retinopathy.

Objective: Diabetic retinopathy (DR), considered one of the most common microvascular complications associated with diabetes mellitus (DM), involves both neuronal and vascular dysfunctions in the retina. Neuronal damage and vision loss occur progressively in patients with DR. A number of genetic targets have been identified for DR and gene-related treatments as well as early diagnostic techniques have been developed.

Colemanite and biological disruptions: Behavioral, neurological, and physiological findings.

Colemanite (COL), a boron-containing mineral, has shown potential therapeutic applications, particularly in the fields of drug delivery and bone health. However, despite its promising bioactive properties, there is a lack of comprehensive toxicological data on its safety, especially regarding its potential medical use. Previous studies have primarily focused on its industrial applications, with limited investigation into its biological effects.

Targeting PKLR in liver diseases.

Pyruvate kinase is a key regulator in hepatic glucose metabolism, encoded by the gene pyruvate kinase liver/red blood cells (PKLR). Systems biology-based approaches, including metabolic and gene co-expression networks analyses, as well as genome-wide association studies (GWAS), have led to the identification of PKLR as a pivotal gene influencing liver metabolism in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC). Here, we review the critical role of PKLR in MASLD and HCC progression and examine the effects of PKLR modulation both in vitro and in vivo.

Synthesis and Characterization of Memantine-Loaded Niosomes for Enhanced Alzheimer's Disease Targeting.

Over the past 25 years, numerous biological molecules, like recombinant lysosomal enzymes, neurotrophins, receptors, and therapeutic antibodies, have been tested in clinical trials for neurological diseases. However, achieving significant success in clinical applications has remained elusive. A primary challenge has been the inability of these molecules to traverse the blood-brain barrier (BBB).

Design, Synthesis, and Computational Evaluation of 3,4-Dihydroquinolin-2()-One Analogues as Potential VEGFR2 Inhibitors in Glioblastoma Multiforme.

: Glioblastoma multiforme (GBM), an aggressive and deadly brain tumour, presents significant challenges in achieving effective treatment due to its resistance to current therapies and poor prognosis. This study aimed to synthesise and evaluate 23 novel analogues of 3,4-dihydroquinolin-2(1)-one, designed to enhance druggability and solubility, and to investigate their potential as VEGFR2 inhibitors for GBM treatment. : The synthesised compounds were analysed using methods, including molecular docking and dynamics studies, to assess their interactions with key residues within the VEGFR2 binding pocket.

Multi-tissue network analysis reveals the effect of JNK inhibition on dietary sucrose-induced metabolic dysfunction in rats.

Excessive consumption of sucrose, in the form of sugar-sweetened beverages, has been implicated in the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD) and other related metabolic syndromes. The c-Jun N-terminal kinase (JNK) pathway plays a crucial role in response to dietary stressors, and it was demonstrated that the inhibition of the JNK pathway could potentially be used in the treatment of MAFLD. However, the intricate mechanisms underlying these interventions remain incompletely understood given their multifaceted effects across multiple tissues.

Integrative proteo-transcriptomic characterization of advanced fibrosis in chronic liver disease across etiologies.

Chronic hepatic injury and inflammation from various causes can lead to fibrosis and cirrhosis, potentially predisposing to hepatocellular carcinoma. The molecular mechanisms underlying fibrosis and its progression remain incompletely understood. Using a proteo-transcriptomics approach, we analyze liver and plasma samples from 330 individuals, including 40 healthy individuals and 290 patients with histologically characterized fibrosis due to chronic viral infection, alcohol consumption, or metabolic dysfunction-associated steatotic liver disease.

Boric acid impedes glioblastoma growth in a rat model: insights from multi-approach analysis.

Limited advancements in managing malignant brain tumors have resulted in poor prognoses for glioblastoma (GBM) patients. Standard treatment involves surgery, radiotherapy, and chemotherapy, which lack specificity and damage healthy brain tissue. Boron-containing compounds, such as boric acid (BA), exhibit diverse biological effects, including anticancer properties.

Synthesis and biological assessment of BUB1B inhibitors for the treatment of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) presents substantial therapeutic challenges due to its molecular heterogeneity, limited response to conventional therapies, and widespread drug resistance. Recent advancements in molecular research have identified novel targets, such as BUB1B, which has been identified through global transcriptomic profiling and gene co-expression network analysis as critical in ccRCC progression. In this study, we synthesized 40 novel derivatives of TG-101209 to modulate BUB1B expression and activity, leading to the induction of apoptosis in Caki-1 cells.

Multi-omics characterization of improved cognitive functions in Parkinson's disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial.

Parkinson's disease is primarily marked by mitochondrial dysfunction and metabolic abnormalities. We recently reported that the combined metabolic activators improved the immunohistochemical parameters and behavioural functions in Parkinson's disease and Alzheimer's disease animal models and the cognitive functions in Alzheimer's disease patients. These metabolic activators serve as the precursors of nicotinamide adenine dinucleotide and glutathione, and they can be used to activate mitochondrial metabolism and eventually treat mitochondrial dysfunction.

Identification of macrophages as an immune suppressor in hepatocellular carcinoma using single-cell and bulk transcriptomics.

Introduction: Macrophages and T cells play crucial roles in liver physiology, but their functional diversity in hepatocellular carcinoma (HCC) remains largely unknown.

Methods: Two bulk RNA-sequencing (RNA-seq) cohorts for HCC were analyzed using gene co-expression network analysis. Key gene modules and networks were mapped to single-cell RNA-sequencing (scRNA-seq) data of HCC.

Assessment of Subacute Toxicity of Ulexite in Rats: Behavioral, Hematological, and Biochemical Insights.

Ulexite (UX), a naturally occurring borate mineral, has gained interest for its diverse industrial applications, yet its toxicological profile remains inadequately characterized. This study aimed to evaluate the subacute toxicity of UX in rats, focusing on behavioral, hematological, and biochemical parameters. Rats were administered UX via gavage at doses of 10, 30, and 300 mg/kg for 7 days.

The Human Pathology Atlas for deciphering the prognostic features of human cancers.

Background: Cancer is one of the leading causes of mortality worldwide, highlighting the urgent need for a deeper molecular understanding and the development of personalized treatments. The present study aims to establish a solid association between gene expression and patient survival outcomes to enhance the utility of the Human Pathology Atlas for cancer research.

Methods: In this updated analysis, we examined the expression profiles of 6918 patients across 21 cancer types.

Identifying Hub Genes and Metabolic Pathways in Collagen VI-Related Dystrophies: A Roadmap to Therapeutic Intervention.

Collagen VI-related dystrophies (COL6RD) are a group of rare muscle disorders caused by mutations in specific genes responsible for type VI collagen production. It affects muscles, joints, and connective tissues, leading to weakness, joint problems, and structural issues. Currently, there is no effective treatment for COL6RD; its management typically addresses symptoms and complications.

Unveiling the Molecular Mechanisms of Glioblastoma through an Integrated Network-Based Approach.

: Despite current treatments extending the lifespan of Glioblastoma (GBM) patients, the average survival time is around 15-18 months, underscoring the fatality of GBM. This study aims to investigate the impact of sample heterogeneity on gene expression in GBM, identify key metabolic pathways and gene modules, and explore potential therapeutic targets. : In this study, we analysed GBM transcriptome data derived from The Cancer Genome Atlas (TCGA) using genome-scale metabolic models (GEMs) and co-expression networks.

Multi-omics analysis reveals the key factors involved in the severity of the Alzheimer's disease.

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder with a global impact, yet its pathogenesis remains poorly understood. While age, metabolic abnormalities, and accumulation of neurotoxic substances are potential risk factors for AD, their effects are confounded by other factors. To address this challenge, we first utilized multi-omics data from 87 well phenotyped AD patients and generated plasma proteomics and metabolomics data, as well as gut and saliva metagenomics data to investigate the molecular-level alterations accounting the host-microbiome interactions.

Discovery of Cell-Permeable Allosteric Inhibitors of Liver Pyruvate Kinase: Design and Synthesis of Sulfone-Based Urolithins.

Metabolic dysfunction-associated fatty liver disease (MAFLD) presents a significant global health challenge, characterized by the accumulation of liver fat and impacting a considerable portion of the worldwide population. Despite its widespread occurrence, effective treatments for MAFLD are limited. The liver-specific isoform of pyruvate kinase (PKL) has been identified as a promising target for developing MAFLD therapies.

Discovery of a Therapeutic Agent for Glioblastoma Using a Systems Biology-Based Drug Repositioning Approach.

Glioblastoma (GBM), a highly malignant tumour of the central nervous system, presents with a dire prognosis and low survival rates. The heterogeneous and recurrent nature of GBM renders current treatments relatively ineffective. In our study, we utilized an integrative systems biology approach to uncover the molecular mechanisms driving GBM progression and identify viable therapeutic drug targets for developing more effective GBM treatment strategies.

Design and evaluation of novel inhibitors for the treatment of clear cell renal cell carcinoma.

The efficacy of conventional chemotherapies in treating clear cell renal cell carcinoma (ccRCC) is often limited due to its high molecular diversity, generally low response rates to standard treatments, and prevalent drug resistance. Recent advancements in the molecular understanding of ccRCC, alongside the discovery of novel therapeutic agents targeting specific proteins, have significantly altered the treatment landscape for ccRCC. Here, we synthesized 27 new compounds that are derivatives of TG-101209 to modulate BUB1B (BUB1 mitotic checkpoint serine/threonine kinase B).

Borax attenuates oxidative stress, inflammation, and apoptosis by modulating Nrf2/ROS balance in acrylamide-induced neurotoxicity in rainbow trout.

Acrylamide (ACR) can have adverse environmental effects because of its multiple applications. Relevant scientific literatures of the existence of ACR residues in foods following processing steps have raised concern in the biochemistry, chemistry and safety of this vinyl substance. The interest has focused on the hepatotoxicity of ACR in animals and humans and on the ACR content mitigation and its detoxification.