Alpinetin protects against myocardial ischemia-reperfusion injury by inhibiting ferroptosis and apoptosis via mitochondrial ferritin.

Purpose: Ischemia-reperfusion injury remains a major problem following myocardial infarction. Alpinetin (ALPT) has been reported to exhibit cardioprotective effects as well as resistance to ischemia-reperfusion injury. However, its role and mechanism during myocardial ischemia-reperfusion injury are unknown.

IPR-dependent Ca signaling in the endoplasmic reticulum is required for deoxynivalenol-induced intestinal stem cell injury.

Deoxynivalenol (DON), a prevalent mycotoxin contaminant in cereals, compromises intestinal homeostasis by inducing organelle dysfunction, particularly in the endoplasmic reticulum (ER). Despite the critical role of ER stress in intestinal pathology, the precise mechanisms by which DON-induced ER dysfunction affects intestinal stem cell (ISC) fate commitment remain unclear. Here, we demonstrate that acute exposure to DON disrupts jejunal epithelial architecture and impairs barrier integrity in piglets by suppressing ISC proliferation and inhibiting differentiation of epithelial lineages along the crypt-villus axis.

Mitochondrial Ferritin Overexpression Attenuates Ferroptosis and Mitochondrial Dysfunction by Reducing VDAC1 to Relieve MI/RI-Induced Damage.

Ischaemic cardiomyopathy is becoming one of the most prevalent cardiovascular diseases among the global elderly population. However, the underlying molecular mechanisms remain incompletely understood. Our previous study demonstrated that VDAC1 plays a significant role in MI/RI.

TSC2/mTORC1 integrates deoxynivalenol signals recognized by membrane receptors IR and EGFR to restrict intestinal stem cell function.

Deoxynivalenol (DON) is a chemically stable mycotoxin with a slow natural degradation rate. Consumption of DON-contaminated food and feed poses significant health risks to human and livestock, leading to reduced productivity and substantial economic losses. The functionality of intestinal stem cells (ISCs) are compromised following sustained intracellular deoxynivalenol (DON) stress.

Discovery of N-(3-fluorophenyl)-2-(4-((7-(1-methyl-1H-pyrazol-4-yl)quinazolin-4-yl)amino)phenyl)acetamide as the first orally active selective aurora kinase B inhibitor.

Cell cycle deregulation is a crucial hallmark of tumorigenesis, leading to uncontrolled cell growth. Overexpression of serine/threonine aurora kinase B (AURKB) is a common feature of human cancer, particularly of the most aggressive subtypes, and it contributes to the alteration of the cell cycle. Thus, AURKB is considered a promising target for cancer treatment; however, no AURKB pharmacological inhibitor has been approved so far.

Iturin A Potentiates Differentiation of Intestinal Epithelial Defense Cells by Modulating Keap1/Nrf2 Signaling to Mitigate Oxidative Damage Induced by Heat-Stable Enterotoxin B.

Intestinal stem cells (ISCs) maintain epithelial renewal through their proliferation and differentiation capabilities, responding to various intestinal insults. However, the impact of iturin A, a natural antimicrobial peptide, on ISC viability and its potential to mitigate heat-stable enterotoxin b (STb)-induced intestinal damage remains unclear. Our recent study demonstrated that oral administration of iturin A enhances tight junction protein expression, accelerates crypt-villus regeneration, and restores epithelial barrier integrity in STb-exposed mice.

The effect of home-based behavioural weight loss combined with pelvic floor muscle training in women seeking weight loss combined with stress urinary incontinence: protocol for a randomised controlled trial.

Introduction: Recent guidelines suggest behavioural weight loss (BWL) and pelvic floor muscle training (PFMT) as first-line treatment approaches for women with both obesity and stress urinary incontinence (SUI). However, the optimal therapeutic and management strategies for these populations remain uncertain.

Methods And Analysis: This assessor-blinded parallel-group randomised controlled trial aims to compare the efficacy of BWL alone, BWL plus conventional PFMT and BWL plus PFMT with a biofeedback device for women who are overweight or obese experiencing SUI or SUI-predominant mixed urinary incontinence.

Morin Reactivates Nrf2 by Targeting Inhibition of Keap1 to Alleviate Deoxynivalenol-Induced Intestinal Oxidative Damage.

As a prevalent mycotoxin found in cereal foods and feed, deoxynivalenol (DON) disrupts the orderly regeneration of intestinal epithelial tissue by interfering with the intracellular antioxidant defense system. However, the potential of mulberry leaf-derived Morin, a natural flavonoid active substance with clearing reactive oxygen species (ROS), to mitigate DON-induced intestinal oxidative damage remains unclear. Our investigation demonstrates that Morin effectively reverses the decline in growth performance and repairs damaged jejunal structures and barrier function under DON exposure.

Suppression of METTL3 expression attenuated matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the extracellular matrix in pelvic organ prolapse.

Background: Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP.

Methods: Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts.

The clinical characteristics and prognosis of surgically treated ovarian endometrioma in pregnant women.

Purpose: To investigate the clinical characteristics and prognosis of surgically treated ovarian endometrioma (OMA) in pregnant women.

Methods: This retrospective cohort study analyzed 30 patients with pathologically confirmed ovarian endometrioma during pregnancy and delivery. Clinical characteristics and follow-up data were summarized.

Matrine disturbs the eimeria necatrix-induced loop of tuft cell-intestinal stem cell-goblet cell by inactivating IL-13/JAK2/STAT3 signaling.

As sensors in the gut, tuft cells integrate a complex array of luminal signals to regulate the differentiation fate of intestinal stem cells (ISCs), which trigger a loop of tuft cell-ISC-goblet cell after parasitic infection. As a plant-derived alkaloid, Matrine plays a prominent role for standardizing ISC functions in Eimeria necatrix (EN)-exposed chicks. In this study, we investigated the modulation effects of Matrine on the specific intestinal epithelial cell loop in EN-exposed chicks in vivo and intestinal organoids (IOs) ex vivo.

Puerarin pretreatment provides protection against myocardial ischemia/reperfusion injury via inhibiting excessive autophagy and apoptosis by modulation of HES1.

The study aimed to elucidate the underlying pharmacological mechanism of the traditional Chinese medicine Pue in ameliorating myocardial ischemia-reperfusion injury (MIRI), a critical clinical challenge exacerbated by reperfusion therapy. In vivo MIRI and in vitro anoxia/reoxygenation (A/R) models were constructed. The results demonstrated that Pue pretreatment effectively alleviated MIRI, as manifested by diminishing the levels of serum CK-MB and LDH, mitigating the extent of myocardial infarction and enhancing cardiac functionality.

The function of SnRK1 in regulating darkness-induced leaf senescence in cucumber.

SnRK1 (SNF1-related kinase 1), a member of the SNF1 protein kinase superfamily, has been demonstrated to play a role in plant growth and development, as well as in stress responses. In this experiment, the leaf senescence of 'Xintaimici' cucumber was simulated by dark treatment and studied using SnRK1 activator/inhibitor and transient transformation technology. The effects of SnRK1 on cucumber leaf senescence, reactive oxygen species (ROS) metabolism, chloroplast structure, and photosynthetic characteristics were studied.

Risk factors for methotrexate treatment failure in tubal ectopic pregnancy: a retrospective cohort study.

Background: Ectopic pregnancy (EP) accounts for approximately 2% of all pregnancies, with tubal ectopic pregnancies (TEPs) being the most common type. Methotrexate (MTX) is a noninvasive and effective medical management option for TEP, but failure rates range from 10 to 36%, posing challenges in clinical practice. Identifying risk factors for MTX treatment failure is crucial to improve patient outcomes and guide clinical decision-making.

Puerarin Protects Myocardium From Ischaemia/Reperfusion Injury by Inhibiting Ferroptosis Through Downregulation of VDAC1.

Despite improvements in interventional techniques leading to faster myocardial reperfusion postmyocardial infarction, there has been a significant rise in the occurrence of myocardial ischaemia/reperfusion injury (MI/RI). A deeper understanding of the underlying mechanisms of MI/RI could offer a crucial approach to reducing myocardial damage and enhancing patient outcomes. This study examined the myocardial protective properties of puerarin (PUE) in the context of MI/RI using hypoxia/reoxygenation (H/R) or ischaemia/reperfusion (I/R) injury models were employed in H9c2 cells and C57BL/6 mice.

Comprehensive analysis of risk factors associated with submucosal invasion in patients with early-stage gastric cancer.

Background: Submucosal invasion in early-stage gastric cancer (GC) is a critical determinant of prognosis and treatment strategy, significantly influencing the risk of lymph node metastasis and recurrence. Identifying risk factors associated with submucosal invasion is essential for optimizing patient management and improving outcomes.

Aim: To comprehensively analyze clinical, imaging, and endoscopic characteristics to identify predictors of submucosal invasion in patients with early-stage differentiated GC.

Health-related quality of life and sexual function among women with overweight or obesity and urinary incontinence: a cross-sectional study.

Purpose: To assess the health related quality of life (HRQoL) and sexual function related to urinary incontinence (UI) severity among women with overweight or obesity.

Methods: From September 2023 to January 2024, a cross-sectional was conducted among women seeking weight loss with overweight or obesity focusing on the symptoms and effects of UI. The degree of UI severity, UI-specific HRQoL, sexual function, and generic HRQoL were detected via Incontinence Modular Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), Incontinence Impact Questionnaire-Short Form (IIQ-7), Short-form Prolapse Incontinence Sexual Questionnaire (PISQ-12), and European Quality of Life-5 Dimensions 5-Level questionnaire (EQ-5D-5 L) respectively.

Integrated analyses of multi-omic data derived from paired primary lung cancer and brain metastasis reveal the metabolic vulnerability as a novel therapeutic target.

Background: Lung cancer brain metastases (LC-BrMs) are frequently associated with dismal mortality rates in patients with lung cancer; however, standard of care therapies for LC-BrMs are still limited in their efficacy. A deep understanding of molecular mechanisms and tumor microenvironment of LC-BrMs will provide us with new insights into developing novel therapeutics for treating patients with LC-BrMs.

Methods: Here, we performed integrated analyses of genomic, transcriptomic, proteomic, metabolomic, and single-cell RNA sequencing data which were derived from a total number of 154 patients with paired and unpaired primary lung cancer and LC-BrM, spanning four published and two newly generated patient cohorts on both bulk and single cell levels.

Generation of BT-Amide, a Bone-Targeted Pyk2 Inhibitor, Effective Oral Administration, for the Prevention of Glucocorticoid-Induced Bone Loss.

Glucocorticoid-induced osteoporosis (GIOP) is the leading cause of iatrogenic osteoporosis due to the widespread clinical use of glucocorticoids (GC) as immunosuppressants. Previous research identified the proline-rich tyrosine kinase 2, Pyk2, as a critical mediator of GC-induced bone loss, and that blocking Pyk2 could protect the skeleton from adverse GC actions. However, systemic administration of current Pyk2 inhibitors causes harmful side effects, such as skin lesions.

Pressure-Mediated Biofeedback With Pelvic Floor Muscle Training for Urinary Incontinence: A Randomized Clinical Trial.

Importance: Supervised pelvic floor muscle training (PFMT) has been recommended as the first-line treatment for women with stress urinary incontinence (SUI), but more evidence on whether adjunctive methods would provide additional benefits is needed.

Objective: To compare the efficacy of PFMT with or without a home-based pressure-mediated biofeedback (BF) device.

Design, Setting, And Participants: This multicenter assessor-blinded randomized clinical trial was conducted in the obstetric clinics of 5 participating tertiary hospitals in China.

Early Weaning Inhibits Intestinal Stem Cell Expansion to Disrupt the Intestinal Integrity of Duroc Piglets via Regulating the Keap1/Nrf2 Signaling.

There are different stress resistance among different breeds of pigs. Changes in intestinal stem cells (ISCs) are still unclear among various breeds of piglets after early weaning. In the current study, Taoyuan Black and Duroc piglets were slaughtered at 21 days of age (early weaning day) and 24 days of age (3 days after early weaning) for 10 piglets in each group.

Causal role of gut microbiota, serum metabolites, immunophenotypes in myocarditis: a mendelian randomization study.

Background: The intricate relationship among gut microbiota, serum metabolites, and immunophenotypes may significantly impact myocarditis. However, direct causal links between these domains and myocarditis are not well understood.

Methods: The study performed Mendelian randomization (MR) analysis using genetic data from public sources.

Combined transcriptome and metabolome analyses reveal the mechanism of abundant bioactive compounds and high antioxidant activity in germinated weedy rice.

Germinated brown rice has recently garnered widespread attention due to its high nutritional value. Previous research demonstrated that the bioactive components and functional properties of germinated brown rice varieties exhibit significant differences. Three germinated rice cultivars weedy rice WR04-6 (WR) and two cultivated rice cultivars with superior eating quality, Koshihikari (YG) and Daohuaxiang (DHX), were analyzed using metabolites and transcriptome profiling.