Identification and validation of CDK1 as a promising therapeutic target for Eriocitrin in colorectal cancer: a combined bioinformatics and experimental approach.

Background: Colorectal cancer (CRC) is a prevalent malignancy worldwide, associated with significant morbidity and mortality. Cyclin-dependent kinase 1 (CDK1) plays a crucial role in cell cycle regulation and has been implicated in various cancers. This study aimed to evaluate the prognostic value of CDK1 in CRC and to identify traditional Chinese medicines (TCM) that can target CDK1 as potential treatments for CRC.

The systemic evolutionary theory of the origin of cancer (SETOC): an update.

The Systemic Evolutionary Theory of the Origin of Cancer (SETOC) is a recently proposed theory founded on two primary principles: the cooperative and endosymbiotic process of cell evolution as described by Lynn Margulis, and the integration of complex systems operating in eukaryotic cells, which is a core concept in systems biology. The SETOC proposes that malignant transformation occurs when cells undergo a continuous adaptation process in response to long-term injuries, leading to tissue remodeling, chronic inflammation, fibrosis, and ultimately cancer. This process involves a maladaptive response, wherein the 'endosymbiotic contract' between the nuclear-cytoplasmic system (derived from the primordial archaeal cell) and the mitochondrial system (derived from the primordial α-proteobacterium) gradually breaks down.

Epigenetic ageing clocks: statistical methods and emerging computational challenges.

Over the past decade, epigenetic clocks have emerged as powerful machine learning tools, not only to estimate chronological and biological age but also to assess the efficacy of anti-ageing, cellular rejuvenation and disease-preventive interventions. However, many computational and statistical challenges remain that limit our understanding, interpretation and application of epigenetic clocks. Here, we review these computational challenges, focusing on interpretation, cell-type heterogeneity and emerging single-cell methods, aiming to provide guidelines for the rigorous construction of interpretable epigenetic clocks at cell-type and single-cell resolution.

A novel cobalt oxide nanoparticle conjugated with ellagic acid arrests the cell cycle in human liver cancer cell line.

The current chemotherapy treatments for liver cancer have shown limited effectiveness. Therefore, there is an urgent need to develop new drugs to combat this disease more effectively. This study reports synthesis of cobalt oxide nanoparticles coated with glucose, and conjugated with Ellagic acid.

ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro.

Despite ongoing antibiotic development, evolution of resistance may render candidate antibiotics ineffective. Here we studied in vitro emergence of resistance to 13 antibiotics introduced after 2017 or currently in development, compared with in-use antibiotics. Laboratory evolution showed that clinically relevant resistance arises within 60 days of antibiotic exposure in Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, priority Gram-negative ESKAPE pathogens.

Pipeline for development of acylated peptide based CGRP receptor antagonist with extended half-life for migraine treatment.

Migraine is a debilitating headache disorder. The disease has neurovascular origin and migraine attacks can be elicited by vasodilative neuropeptides such as alpha calcitonin gene-related peptide (αCGRP). Antagonizing CGRP actions in migraine patients has proven clinically efficient.

Integrating machine learning and structure-based approaches for repurposing potent tyrosine protein kinase Src inhibitors to treat inflammatory disorders.

Tyrosine-protein kinase Src plays a key role in cell proliferation and growth under favorable conditions, but its overexpression and genetic mutations can lead to the progression of various inflammatory diseases. Due to the specificity and selectivity problems of previously discovered inhibitors like dasatinib and bosutinib, we employed an integrated machine learning and structure-based drug repurposing strategy to find novel, targeted, and non-toxic Src kinase inhibitors. Different machine learning models including random forest (RF), k-nearest neighbors (K-NN), decision tree, and support vector machine (SVM), were trained using already available bioactivity data of Src kinase targeting compounds.

Involvement of p38 MAPK and MAPKAPK2 in promoting cell death and the inflammatory response to ischemic stress associated with necrotic glioblastoma.

The association of necrosis in tumors with poor prognosis implies a potential tumor-promoting role. However, the mechanisms underlying cell death in this context and how damaged tissue contributes to tumor progression remain unclear. Here, we identified p38 mitogen-activated protein kinases (p38 MAPK, a.

Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencing.

Maturation of αβ lineage T cells in the thymus relies on the formation and cell surface expression of a pre-T cell receptor (TCR) complex, composed of TCRβ chain and pre-TCRα (pTCRα) chain heterodimers, giving rise to a diverse T cell repertoire. Genetic aberrations in key molecules involved in T cell development lead to profound T cell immunodeficiency. Definitive genetic diagnosis guides treatment choices and counseling.

The Role of Primary Cilia in Myoblast Proliferation and Cell Cycle Regulation during Myogenesis.

The process of mammalian myogenesis is fundamental to understanding muscle development and holds broad relevance across multiple fields, from developmental biology to regenerative medicine. This review highlights two key aspects: myoblast proliferation and the role of cilia in this process. Myoblasts, as muscle precursor cells, must undergo tightly regulated cycles of proliferation and differentiation to ensure proper muscle growth and function.

In vitro analysis of composition profiles of resins for 3D printing of dentures.

Objective: This study aimed to investigate the resin compounds from CAD-CAM 3D-printed denture resins, focusing on the identification and classification of free monomers and other components. The primary objective was to determine the chemical profile of these 3D-prinding resin materials.

Methods: Four 3D-printed denture resins, two base materials (1: DentaBASE, Asiga Ltd.

Fabrication and characterization of silver nanowire-coated porous alginate wet-laid webs for wound dressing applications.

Wound care presents an imposed financial burden for healthcare organizations, prompting the need for novel and cost-efficient dressings. In this study, we address this challenge by introducing a novel approach to fabricate antibacterial alginate-based fibrous materials using a combination of wet spinning and the wet-laying method, which offer advantages including structural and functional properties such as breathability, nontoxicity, biocompatibility, and cost-effectiveness. The wet spinning method was employed to develop porous and non-porous Ca-alginate fibers with diameters of 100 ± 4.

Emergence of fungal hybrids - potential threat to humans.

Fungal hybrids arise through the interbreeding of distinct species. This hybridization process fosters increased genetic diversity and the emergence of new traits. Mechanisms driving hybridization include the loss of heterozygosity, copy number variations, and horizontal gene transfer.

Distinguishing abiotic corrosion from two types of microbiologically influenced corrosion (MIC) using a new electrochemical biofilm/MIC test kit.

Biofilms can cause biofouling, water quality deterioration, and transmission of infectious diseases. They are also responsible for microbiologically influenced corrosion (MIC) which can cause leaks, resulting in environmental disasters. A new disposable biofilm/MIC test kit was demonstrated to distinguish abiotic corrosion of carbon steel from MIC.

A divergent two-domain structure of the anti-Müllerian hormone prodomain.

TGFβ family ligands are synthesized as precursors consisting of an N-terminal prodomain and C-terminal growth factor (GF) signaling domain. After proteolytic processing, the prodomain typically remains noncovalently associated with the GF, sometimes forming a high-affinity latent procomplex that requires activation. For the TGFβ family ligand anti-Müllerian hormone (AMH), the prodomain maintains a high-affinity interaction with its GF that does not render it latent.

Exercise intensity and training alter the innate immune cell type and chromosomal origins of circulating cell-free DNA in humans.

Exercising regularly promotes health, but these benefits are complicated by acute inflammation induced by exercise. A potential source of inflammation is cell-free DNA (cfDNA), yet the cellular origins, molecular causes, and immune system interactions of exercise-induced cfDNA are unclear. To study these, 10 healthy individuals were randomized to a 12-wk exercise program of either high-intensity tactical training (HITT) or traditional moderate-intensity training (TRAD).

Unseen Threats: The Long-term Impact of PET-Microplastics on Development of Male Reproductive Over a Lifetime.

The physical abrasion of plastics from simple everyday entered the food chain, with associated risks recently emphasized. Although many studies have reported the adverse effects of microplastics (MPs) on human, the reproductive implications of continuous exposure to physically abraded polyethylene terephthalate (PET)-MPs remain unexplored. Ingestion of physically abraded PET-MPs (size range: 50-100 µm) in mice from 5 to 34 weeks of age at an annual intake relevant dose of MPs (5 mg week) significantly impaired male reproductive function.

Senescent cell-derived extracellular vesicles inhibit cancer recurrence by coordinating immune surveillance.

Senescence is a non-proliferative, survival state that cancer cells can enter to escape therapy. In addition to soluble factors, senescence cells secrete extracellular vesicles (EVs), which are important mediators of intercellular communication. To explore the role of senescent cell-derived EVs (senEVs) in inflammatory responses to senescence, we developed an engraftment-based senescence model in wild-type mice and genetically blocked senEV release in vivo, without significantly affecting soluble mediators.

An Albumin-Photosensitizer Supramolecular Assembly with Type I ROS-Induced Multifaceted Tumor Cell Deaths for Photodynamic Immunotherapy.

Photodynamic therapy holds great potentials in cancer treatment, yet its effectiveness in hypoxic solid tumor is limited by the oxygen-dependence and insufficient oxidative potential of conventional type II reactive oxygen species (ROS). Herein, the study reports a supramolecular photosensitizer, BSA@TPE-BT-SCT NPs, through encapsulating aggregation-enhanced emission photosensitizer by bovine serum albumin (BSA) to significantly enhance ROS, particularly less oxygen-dependent type I ROS for photodynamic immunotherapy. The abundant type I ROS generated by BSA@TPE-BT-SCT NPs induce multiple forms of programmed cell death, including apoptosis, pyroptosis, and ferroptosis.

Dialogue mechanisms between astrocytic and neuronal networks: A whole-brain modelling approach.

Astrocytes critically shape whole-brain structure and function by forming extensive gap junctional networks that intimately and actively interact with neurons. Despite their importance, existing computational models of whole-brain activity ignore the roles of astrocytes while primarily focusing on neurons. Addressing this oversight, we introduce a biophysical neural mass network model, designed to capture the dynamic interplay between astrocytes and neurons via glutamatergic and GABAergic transmission pathways.

The piRNA protein Asz1 is essential for germ cell and gonad development in zebrafish and exhibits differential necessities in distinct types of germ granules.

Germ cells are essential for fertility, embryogenesis, and reproduction. Germline development requires distinct types of germ granules, which contains RNA-protein (RNP) complexes, including germ plasm in embryos, piRNA granules in gonadal germ cells, and the Balbiani body (Bb) in oocytes. However, the regulation of RNP assemblies in zebrafish germline development are still poorly understood.

Increased resting heart rate indicates high-workload hearts with augmented aortic hydraulic power in hypertensive pigs.

Clarifying the inceptive pathophysiology of hypertensive heart disease helps to impede the disease progression. Through coarctation of the infrarenal abdominal aorta (AA), we induced hypertension in minipigs and evaluated physiological reactions and morpho-functional changes of the heart. Moderate aortic coarctation was achieved with approximately 30 mmHg systolic pressure gradient in minipigs.

Single Extracellular VEsicle Nanoscopy-Universal Protocol (SEVEN-UP): Accessible Imaging Platform for Quantitative Characterization of Single Extracellular Vesicles.

Extracellular vesicles (EVs), membrane-encapsulated nanoparticles shed from all cells, are tightly involved in critical cellular functions. Moreover, EVs have recently emerged as exciting therapeutic modalities, delivery vectors, and biomarker sources. However, EVs are difficult to characterize, because they are typically small and heterogeneous in size, origin, and molecular content.

Emerging Trends in Neuroblastoma Diagnosis, Therapeutics, and Research.

This review explores the current understanding and recent advancements in neuroblastoma, one of the most common extracranial solid pediatric cancers, accounting for ~ 15% of childhood cancer-related mortality. The hallmarks of NBL, including angiogenesis, metastasis, apoptosis resistance, cell cycle dysregulation, drug resistance, and responses to hypoxia and ROS, underscore its complex biology. The tumor microenvironment's significance in disease progression is acknowledged in this study, along with the pivotal role of cancer stem cells in sustaining tumor growth and heterogeneity.

MiRNAs and tempol therapeutic potential in prostate cancer: a preclinical approach.

This study investigated tempol action on genes and miRNAs related to NFκB pathway in androgen dependent or independent cell lines and in TRAMP model in the early and late-stages of cancer progression. A bioinformatic search was conducted to select the miRNAs to be measured based on the genes of interest from NFκB pathway. The miR-let-7c-5p, miR-26a-5p and miR-155-5p and five target genes (BCL2, BCL2L1, RELA, TNF, PTGS2) were chosen for RT-PCR and gene enrichment analyses.