Role of gut microbiota and fecal metabolites in the protective effect of soybean pulp-rich diet against estrogen-induced cholestasis in rats.

This study was designed to explore the role of gut microbiota and its metabolites in the treatment of estrogen-induced cholestasis (EIC) in rats with a soybean pulp-rich diet and to clarify the effects of daidzein (DAI), a principal active ingredient of soybean pulp. The findings demonstrated that the soybean pulp-rich diet could relieve cholestasis by decreasing the levels of total bile acids (TBA) and alkaline phosphatase and enhancing the bile flow rate. Through gut microbiota and metabolomics analyses, it was revealed that this diet might alter the abundances of certain bacterial taxa including , , and , thus influencing lipid metabolism, tryptophan metabolism, and steroid metabolism, which led to disparities between the groups fed with and without the soybean pulp-rich diet.

SMAC-armed oncolytic virotherapy enhances the anticancer activity of PD1 blockade by modulating PANoptosis.

Background: Oncolytic viruses (OVs) are increasingly recognized as promising tools for cancer therapy, as they selectively infect and destroy tumor cells while leaving healthy cells unharmed. Despite considerable progress, the limited therapeutic efficacy of OV-based virotherapy continues to be a significant challenge in cancer treatment.

Methods: The SMAC/DIABLO gene was inserted into the genome of vesicular stomatitis virus (VSV) to generate VSV-S.

Endothelial cell-selective adhesion molecule deficiency exhibits increased pulmonary vascular resistance due to impaired endothelial nitric oxide signaling.

Endothelial cell-selective adhesion molecule (ESAM) is a member of tight junction molecules, highly abundant in the heart and the lung, and plays a role in regulating endothelial cell permeability. We previously reported that mice with genetic ESAM deficiency () exhibit coronary microvascular dysfunction leading to the development of left ventricular diastolic dysfunction. Here, we hypothesize that mice display impairments in the pulmonary vasculature, affecting the overall pulmonary vascular resistance (PVR).

Therapeutic Targeting of the GLS1-c-Myc Positive Feedback Loop Suppresses Glutaminolysis and Inhibits Progression of Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is addicted to glutaminolysis. Targeting this metabolic dependency has emerged as a potential therapeutic approach for HNSCC. In this study, we conducted a bioinformatic analysis of The Cancer Genome Atlas HNSCC cohort that revealed a robust correlation between expression of MYC (encoding the protein c-Myc) and glutaminase 1 (GLS1), which catalyzes the first step in glutaminolysis.

Phosphodiesterase 9A inhibition improves aging-related increase in pulmonary vascular resistance in mice.

As individuals age, there is a gradual decline in cardiopulmonary function, often accompanied by cardiac pump dysfunction leading to increased pulmonary vascular resistance (PVR). Our study aims to investigate the changes in cardiac and pulmonary vascular function associated with aging. Additionally, we aim to explore the impact of phosphodiesterase 9A (PDE9A) inhibition, which has shown promise in treating cardiometabolic diseases, on addressing left ventricle (LV) dysfunction and elevated PVR in aging individuals.

Modulation of Dendritic Cell Function via Nanoparticle-Induced Cytosolic Calcium Changes.

Calcium nanoparticles have been investigated for applications, such as drug and gene delivery. Additionally, Ca serves as a crucial second messenger in the activation of immune cells. However, few studies have systematically studied the effects of calcium nanoparticles on the calcium levels and functions within immune cells.

Adaptive c-Met-PLXDC2 Signaling Axis Mediates Cancer Stem Cell Plasticity to Confer Radioresistance-associated Aggressiveness in Head and Neck Cancer.

Unlabelled: Radiotherapy plays an essential role in the treatment of head and neck squamous cell carcinoma (HNSCC), yet radioresistance remains a major barrier to therapeutic efficacy. A better understanding of the predominant pathways determining radiotherapy response could help develop mechanism-informed therapies to improve cancer management. Here we report that radioresistant HNSCC cells exhibit increased tumor aggressiveness.

Mice with endothelial cell-selective adhesion molecule deficiency develop coronary microvascular rarefaction and left ventricle diastolic dysfunction.

Endothelial cell-selective adhesion molecule (ESAM) regulates inflammatory cell adhesion and transmigration and promotes angiogenesis. Here, we examined the role of ESAM in cardiac vascularization, inflammatory cell infiltration, and left ventricle (LV) diastolic function under basal and hemodynamic stress conditions. We employed mice with homozygous genetic deletion of ESAM (ESAM ) and also performed uninephrectomy and aldosterone infusion (UNX-Aldo) to induce volume and pressure overload.

The role of ADAM17 in cerebrovascular and cognitive function in the APP/PS1 mouse model of Alzheimer's disease.

Introduction: The disintegrin and metalloproteinase 17 (ADAM17) exhibits α-secretase activity, whereby it can prevent the production of neurotoxic amyloid precursor protein-α (APP). ADAM17 is abundantly expressed in vascular endothelial cells and may act to regulate vascular homeostatic responses, including vasomotor function, vascular wall morphology, and formation of new blood vessels. The role of vascular ADAM17 in neurodegenerative diseases remains poorly understood.

Validation of MAPK signalling pathway as a key role of paeoniflorin in the treatment of intrahepatic cholestasis of pregnancy based on network pharmacology and metabolomics.

Numerous studies have clarified the effectiveness of paeoniflorin in the treatment of cholestasis. However, the therapeutic efficacy and mechanisms of action of paeoniflorin in intrahepatic cholestasis of pregnancy (ICP) were still unknown. This study aimed to investigate the molecular biological mechanisms of paeoniflorin against ICP by combining network pharmacology and metabolomics.

Evaluation of the Efficacy of Saracatinib-Loaded Nanoparticles in Lymphatic Metastases of HNSCC with the Aid of Bioluminescence Imaging.

Head and neck squamous cell carcinoma (HNSCC) remains a deadly disease despite concerted efforts to improve its diagnosis and treatment in recent decades. Metastasis of advanced HNSCC nearly always occurs first in neck lymph nodes before the development of distant metastasis. However, the development of preclinical animal models and therapeutic treatments for metastatic HNSCC is lagged from bench to clinic.

The Association Between the Albumin and Viral Negative Conversion Rate in Patients Infected with Novel Coronavirus Disease 2019 (COVID-19).

Purpose: The novel coronavirus disease 2019 (COVID-19) epidemic is the severe global pandemic with large numbers of infected cases and deaths in recent decades. The previous studies were all about the influence of albumin (ALB) for the severity and mortality of in-patients infected with COVID-19. But few studies exist about the influence factors to achieve viral negative conversion.

ATAD3A mediates activation of RAS-independent mitochondrial ERK1/2 signaling, favoring head and neck cancer development.

Background: Targeting mitochondrial oncoproteins presents a new concept in the development of effective cancer therapeutics. ATAD3A is a nuclear-encoded mitochondrial enzyme contributing to mitochondrial dynamics, cholesterol metabolism, and signal transduction. However, its impact and underlying regulatory mechanisms in cancers remain ill-defined.

Blockade of glutamine-dependent cell survival augments antitumor efficacy of CPI-613 in head and neck cancer.

Background: Alterations in metabolism are one of the emerging hallmarks of cancer cells and targeting dysregulated cancer metabolism provides a new approach to developing more selective therapeutics. However, insufficient blockade critical metabolic dependencies of cancer allows the development of metabolic bypasses, thus limiting therapeutic benefits.

Methods: A series of head and neck squamous cell carcinoma (HNSCC) cell lines and animal models were used to determine the efficacy of CPI-613 and CB-839 when given alone or in combination.

FGF19/FGFR4 signaling axis confines and switches the role of melatonin in head and neck cancer metastasis.

Background: There is no consensus about the effective dosages of melatonin in cancer management, thus, it is imperative to fully understand the dose-dependent responsiveness of cancer cells to melatonin and the underlying mechanisms.

Methods: Head and neck squamous cell carcinoma (HNSCC) cells with or without melatonin treatment were used as a research platform. Gene depletion was achieved by short hairpin RNA, small interfering RNA, and CRISPR/Cas9.

Emerging Links between Control of Mitochondrial Protein ATAD3A and Cancer.

Spanning from the mitochondria's outer surface to the inner membrane, the nuclear-encoded protein ATAD3A maintains vital roles in regulating mitochondrial dynamics, homeostasis, metabolism, and interactions with the endoplasmic reticulum. Recently, elevated levels of ATAD3A have been reported in several types of cancer and to be tightly correlated with cancer development and progression, including increased cancer cell potential of proliferation, metastasis, and resistance to chemotherapy and radiotherapy. In the current review, we reveal ATAD3A as the link between mitochondrial functions and cancer biology and the accumulating evidence presenting ATAD3A as an attractive target for the development of novel cancer therapy to inhibit aberrant cancer metabolism and progression.

Visualizing and Evaluating Cancer Cell Growth and Invasion by a Novel 3D Culture System.

With the development of new materials and technologies, it is possible to access gene function and drug metabolism using a three-dimensional (3D) cell culture system, which is more suitable for mimicking the in vivo microenvironment of cultured tumor cells ex vivo. SeedEZ is a novel and versatile tool that allows culturing of different types of cells with user convenience and in a desired sequence. This system provides a bridge between traditional 2D culture and animal experiments.

Using Genome-Editing Tools to Develop a Novel In Situ Coincidence Reporter Assay for Screening ATAD3A Transcriptional Inhibitors.

Transgene-based reporter gene assays have been used for discovery of inhibitors targeting vital gene transcription. In traditional assays, the reporter gene is commonly fused with a cloned promoter and integrated into a random genomic location. This has been widely applied but significantly dampened by disadvantages, including incomplete cis-acting elements, the influence of foreign epigenetic environments, and generation of false hits that disrupt the luciferase reporter activity.

Simultaneous Determination of Schisandrin and Promethazine with Its Metabolite in Rat Plasma by HPLC-MS/MS and Its Application to a Pharmacokinetic Study.

This study aimed to develop a selective, simple, and sensitive HPLC-MS/MS method for the simultaneous determination of schisandrin and promethazine (PMZ) with its metabolite in rat plasma, which was further used for a pharmacokinetic herb-drug interaction study. HPLC-MS/MS analyses were performed on an Agilent Technologies 1290 LC and a 6410 triple quadrupole mass spectrometer. The following parameters, the lower limit of quantification (LLOQ), calibration curve, accuracy, precision, stability, matrix effect, and recovery, were validated.

Pharmacokinetics of Sublingual Buprenorphine Tablets Following Single and Multiple Doses in Chinese Participants With and Without Opioid Use Disorder.

Background: Two phase I studies assessed the pharmacokinetics of buprenorphine, its metabolite norbuprenorphine, and naloxone following administration of buprenorphine/naloxone sublingual tablets in Chinese participants.

Methods: In the first phase I, open-label, single ascending-dose (SAD) study, 82 opioid-naïve volunteers received a single buprenorphine/naloxone dose ranging from 2 mg/0.5 mg to 24 mg/6 mg while under naltrexone block.