Matrix Metalloproteinase-9 is associated with tumor microenvironment remodeling of bladder cancer.

Tumor microenvironment (TME) takes an essential part in the bladder cancer progression, which is associated with intercellular cross-talk between stroma cells and cancer. We aimed use bioinformatics tools to analyze tumor microenvironment remodeling in bladder cancer. CIBERSORT and ESTIMATE are bioinformatics tools based on deconvolution for calculating proportions of tumor-infiltrating immune cells and stromal components in TME.

Consequences of insecticide overuse in Hungary: assessment of pyrethroid resistance in Culex pipiens and Aedes albopictus mosquitoes.

Background: Mosquitoes, as vectors of various pathogens, have been a public health risk for centuries. Human activities such as international travel and trade, along with climate change, have facilitated the spread of invasive mosquitoes and novel pathogens across Europe, increasing the risk of mosquito-borne disease introduction and their spread. Despite this threat, mosquito control in Hungary still relies predominantly on chemical treatments, which poses the risk of developing insecticide resistance in local populations.

Increased pro-SFTPB in HDL promotes the pro-inflammatory transition of HDL and represents a sign of poor prognosis in ARDS patients.

Background: Acute respiratory distress syndrome (ARDS) is causatively associated with excessive alveolar inflammation involving deregulated pro-inflammatory macrophage polarization. High-density lipoprotein (HDL) showed critical anti-inflammatory roles by modulating macrophage function, and its adverse transition to pro-inflammation has an important role in the pathogenesis of ARDS. However, the relationship between HDL protein constituents and functional remodeling is unknown in ARDS.

Organoid development and applications in gynecological cancers: the new stage of tumor treatment.

Gynecologic cancers (GCs), including cervical cancer (CC), ovarian cancer (OC), endometrial cancer (EC), as well as vulvar and vaginal cancers, represent major health threats to women, with increasing incidence rates observed globally. Conventional treatments, such as surgery, radiation therapy, and chemotherapy, are often hindered by challenges such as drug resistance and recurrence, contributing to high mortality rates. Organoid technology has emerged as a transformative tool in cancer research, offering in vitro models that closely replicate the tumor cell architecture and heterogeneity of primary cancers.

Age-specific prognosis of acute and steady minor elevations in cardiac troponin among non-acute myocardial infarction inpatients: a large real-world cohort study.

Background: The upper reference limit of normal (ULN) of cardiac troponin (cTn) for older adults can be higher than for young adults, while the same ULN is used for both older and young adults in the current clinical practice.

Methods: In this multicentre longitudinal cohort study, non-acute myocardial infarction (non-AMI) inpatients with at least two cTn concentrations hospitalised between 2013 and 2022 in the Tianjin Health and Medical Data Platform were included. Multivariable Cox proportional hazards and landmark regression models were used to estimate the risk of in-hospital, 30-day and 1-year mortality in different cTn groups (normal, stable minor elevation (1-2×ULN with variation ≤20%), acute minor elevation (1-2×ULN with variation >20%) and apparent elevation (>2×ULN)).

Tissue-specific roles of de novo DNA methyltransferases.

DNA methylation, catalyzed by DNA methyltransferases (DNMT), plays pivotal role in regulating embryonic development, gene expression, adaption to environmental stress, and maintaining genome integrity. DNMT family consists of DNMT1, DNMT3A, DNMT3B, and the enzymatically inactive DNMT3L. DNMT3A and DNMT3B establish novel methylation patterns maintained by DNMT1 during replication.

Building Public Health Quantitative Methods Capacity and Networks in sub-Saharan Africa: An Evaluation of a Faculty Training Program.

Introduction: There is a shortage of individuals trained in using quantitative methods in biomedical research in sub-Saharan Africa (SSA). Improving public health in SSA requires new ways to promote quantitative knowledge and skills among faculty in biomedical research and better-integrated network systems of support.

Methods: We describe the development, implementation, and evaluation of an innovative faculty training and support program in SSA from December 2017-June 2020, using courses in monitoring and evaluation, data management, and complex surveys as prototypical examples.

Early and delayed STAT1-dependent responses drive local trained immunity of macrophages in the spleen.

Trained immunity (TI) is the process wherein innate immune cells gain functional memory upon exposure to specific ligands or pathogens, leading to augmented inflammatory responses and pathogen clearance upon secondary exposure. While the differentiation of hematopoietic stem cells (HSCs) and reprogramming of bone marrow (BM) progenitors are well-established mechanisms underpinning durable TI protection, remodeling of the cellular architecture within the tissue during TI remains underexplored. Here, we study the effects of peritoneal Bacillus Calmette-Guérin (BCG) administration to find TI-mediated protection in the spleen against a subsequent heterologous infection by the Gram-negative pathogen Typhimurium (.

Hemoglobin mass is accurately predicted in endurance athletes.

Hemoglobin mass (Hb) prediction enhance the accessibility and practicality of athletes' hemoglobin status monitoring, facilitating better performance. Therefore, we aimed to create prediction equations for Hb in well-trained endurance athletes (EA), based on easily obtained measures. The population of 220 well-trained EA (40% females, maximal oxygen uptake = 63.

Advancing COVID-19 Treatment: The Role of Non-covalent Inhibitors Unveiled by Integrated Machine Learning and Network Pharmacology.

Introduction: The COVID-19 pandemic has necessitated rapid advancements in therapeutic discovery. This study presents an integrated approach combining machine learning (ML) and network pharmacology to identify potential non-covalent inhibitors against pivotal proteins in COVID-19 pathogenesis, specifically B-cell lymphoma 2 (BCL2) and Epidermal Growth Factor Receptor (EGFR).

Method: Employing a dataset of 13,107 compounds, ML algorithms such as k-Nearest Neighbors (kNN), Support Vector Machine (SVM), Random Forest (RF), and Naïve Bayes (NB) were utilized for screening and predicting active inhibitors based on molecular features.

CausalXtract, a flexible pipeline to extract causal effects from live-cell time-lapse imaging data.

Live-cell microscopy routinely provides massive amounts of time-lapse images of complex cellular systems under various physiological or therapeutic conditions. However, this wealth of data remains difficult to interpret in terms of causal effects. Here, we describe CausalXtract, a flexible computational pipeline that discovers causal and possibly time-lagged effects from morphodynamic features and cell-cell interactions in live-cell imaging data.

Unveiling the immunomodulatory dance: endothelial cells' function and their role in non-small cell lung cancer.

The dynamic interactions between tumor endothelial cells (TECs) and the immune microenvironment play a critical role in the progression of non-small cell lung cancer (NSCLC). In general, endothelial cells exhibit diverse immunomodulatory properties, influencing immune cell recruitment, antigen presentation, and regulation of immune checkpoint expression. Understanding the multifaceted roles of TECs as well as assigning specific functional hallmarks to various TEC phenotypes offer new avenues for targeted development of therapeutic interventions, particularly in the context of advanced immunotherapy and anti-angiogenic treatments.

Prostate cancer cells elevate glycolysis and G6PD in response to caffeic acid phenethyl ester-induced growth inhibition.

Background: Caffeic acid phenethyl ester (CAPE) is the main bioactive component of poplar type propolis. We previously reported that treatment with caffeic acid phenethyl ester (CAPE) suppressed the cell proliferation, tumor growth, as well as migration and invasion of prostate cancer (PCa) cells via inhibition of signaling pathways of AKT, c-Myc, Wnt and EGFR. We also demonstrated that combined treatment of CAPE and docetaxel altered the genes involved in glycolysis and tricarboxylic acid (TCA) cycle.

Evaluation of multidrug resistance in the Gram-negative microbiome of cancer patients and the adverse effects of their metabolites on albino rats and epithelial or fibroblasts cell lines.

Background: Cancer is a significant global health issue due to its high incidence and mortality rates. In recent years, the relationship between the human microbiota and cancer has garnered attention across various medical fields. This includes research into the microbial communities that influence cancer development, tumor-associated microorganisms, and the interactions between the microbiome and tumor, collectively referred to as the oncobiome.

Unraveling calcium dysregulation and autoimmunity in immune mediated rippling muscle disease.

Rippling Muscle Disease (RMD) is a rare skeletal myopathy characterized by abnormal muscular excitability manifesting with wave-like muscle contractions and percussion-induced muscle mounding. Hereditary RMD is associated with caveolin-3 or cavin-1 mutations. Recently, we identified cavin 4 autoantibodies as a biomarker of immune-mediated RMD (iRMD), though the underlying disease-mechanisms remain poorly understood.

Coralyne Targets the Catalytic Domain of MMP9: An In Silico and In Vitro Investigation.

Coralyne (COR) is a protoberberine-like isoquinoline alkaloid, and it is known for double-stranded (ds) DNA intercalation and topoisomerase inhibition. It can also sensitize cancer cells through various mechanisms. COR reduces the proliferation and migration of breast cancer cells by inhibiting the expression and activity of matrix metalloproteinase 9 (MMP9).

Evaluation of ACE I/D and ATIR A1166C variants in patients with diabetes mellitus with and without peripheral neuropathy in Turkish patients.

Objective: Type 2 Diabetes Mellitus (T2DM) can lead to long-term vascular complications such as diabetic peripheral neuropathy (DPN). This study aimed to investigate the role of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) and angiotensin II type 1 receptor (AT1R) A1166C variants in the predisposition to T2DM in the Turkish population and their association with DPN.

Methods: The study included 90 T2DM patients (42 with DPN) and 50 healthy individuals.

The role of exosomal hsa-miR-125b-5p and hsa-miR-320c as non-invasive biomarkers in high-radon areas of Kazakhstan.

Background: Radon, a radioactive gas, is a significant risk factor for lung cancer, especially in non-smokers. This study examines the expression of exosomal microRNAs (miRNAs) as potential biomarkers for radon-induced effects.

Methods: A total of 109 participants from high- and low-radon areas in Kazakhstan were included.

How do lifestyle and environmental factors influence the sperm epigenome? Effects on sperm fertilising ability, embryo development, and offspring health.

Recent studies support the influence of paternal lifestyle and diet before conception on the health of the offspring via epigenetic inheritance through sperm DNA methylation, histone modification, and small non-coding RNA (sncRNA) expression and regulation. Smoking may induce DNA hypermethylation in genes related to anti-oxidation and insulin resistance. Paternal diet and obesity are associated with greater risks of metabolic dysfunction in offspring via epigenetic alterations in the sperm.

Whole-genome sequencing-based characterization of Salmonella enterica Serovar Enteritidis and Kentucky isolated from laying hens in northwest of Iran, 2022-2023.

Background: The transmission of Salmonella spp. to human through the consumption of contaminated food products of animal origin, mainly poultry is a significant global public health concern. The emerging multidrug resistant (MDR) clones of non-typhoidal Salmonella (NTS) serovars, have spread rapidly worldwide both in humans and in the food chain.

Dual VEGFR-2 and EGFR inhibitors of phenyldiazenes: anticancer evaluations, ADMET, docking, design and synthesis.

Aim: New phenyldiazene scaffold-linked heterocyclic pyrazole, pyrimidinone, pyrimidinthione, and/or triazine rings have been developed and synthesized.

Methods & Results: Cytotoxicity of our derivatives was estimated on four cancer and VERO normal cell lines targeting EGFR (epidermal growth factor receptor) and VEGFR-2 (vascular endothelial growth factor receptor-2) enzymes. Our new derivatives selectively inhibited both VEGFR-2 and EGFR as they have the essential structural requirements for inhibitors of both receptors.

Sex differences in the murine HPA axis after acute and repeated restraint stress.

Chronic stress and stress-related mental illnesses such as major depressive disorder (MDD) constitute some of the leading causes of disability worldwide with a higher prevalence in women compared to men. However, preclinical research into stress and MDD is heavily biased toward using male animals only. Aberrant activity of the hypothalamic-pituitary-adrenal (HPA) axis has been linked to the development of MDD and several animal models of MDD have been established based on HPA axis dysregulation.

High-level biosynthesis and purification of the antimicrobial peptide Kiadin based on non-chromatographic purification and acid cleavage methods.

Antimicrobial peptides (AMPs) are renowned for their potent bacteriostatic activity and safety, rendering them invaluable in animal husbandry, food safety, and medicine. Despite their potential, the physiological toxicity of AMPs to host cells significantly hampers their biosynthetic production. This study presents a novel approach for the biosynthesis of the antimicrobial peptide Kiadin by engineering a DAMP4-DPS-Kiadin fusion protein to mitigate host cell toxicity and achieve high-level expression.

Neurons Are Not All the Same: Diversity in Neuronal Populations and Their Intrinsic Responses to Spinal Cord Injury.

Functional recovery following spinal cord injury will require the regeneration and repair of damaged neuronal pathways. It is well known that the tissue response to injury involves inflammation and the formation of a glial scar at the lesion site, which significantly impairs the capacity for neuronal regeneration and functional recovery. There are initial attempts by both supraspinal and intraspinal neurons to regenerate damaged axons, often influenced by the neighboring tissue pathology.

Characterization of the genomic landscape in liver oligometastatic NSCLC.

Objectives: Emerging data have shown that local treatment could provide clinical benefit for non-small cell lung cancer (NSCLC) patients with oligometastasis. Liver metastases have the worst prognosis in advanced NSCLC, but the genomic characteristics of liver oligometastasis remain unclear. The aim of our study was to elucidate the molecular features of liver oligometastatic NSCLC.