Insights into NEK2 inhibitors as antitumor agents: From mechanisms to potential therapeutics.

NEK2, a serine/threonine protein kinase, is integral to mitotic events such as centrosome duplication and separation, microtubule stabilization, spindle assembly checkpoint, and kinetochore attachment. However, NEK2 overexpression leads to centrosome amplification and chromosomal instability, which are significantly associated with various malignancies, including liver, breast, and non-small cell lung cancer. This overexpression could facilitate tumor development and confer resistance to therapy by promoting aberrant cell division and centrosome amplification.

Prevalence of Microsatellite Instability in Gastric and Gastroesophageal Junction Cancer patients from a Latin American Country.

Background: In Colombia, gastric cancer is fifth in incidence (12.8 cases per 100,000) and third in mortality (9.9 cases per 100,000).

Olanzapine/Samidorphan Effects on Weight Gain: An Individual Patient Data Meta-Analysis of Phase 2 and 3 Randomized Double-Blind Studies.

To evaluate weight change with a combination of olanzapine and samidorphan (OLZ/SAM) versus olanzapine by pooling data across clinical studies. This study was an individual patient data (IPD) meta-analysis of clinical trial data. EMBASE, MEDLINE, and PsycInfo were searched for randomized clinical trials (≥12 weeks) in adults with schizophrenia or bipolar I disorder in which weight change from baseline was the primary or secondary end point.

Proteomic characterization and comparison of the infective and adult life stage secretomes from Necator americanus and Ancylostoma ceylanicum.

More than 470 million people globally are infected with the hookworms Ancylostoma ceylanicum and Necator americanus, resulting in an annual loss of 2.1 to 4 million disability-adjusted-life-years. Current infection management approaches are limited by modest drug efficacy, the costs associated with frequent mass drug administration campaigns, and the risk of reinfection and burgeoning drug resistance.

Characterization of Tumor Antigens from Multi-omics Data: Computational Approaches and Resources.

Tumor-specific antigens, also known as neoantigens, have potential utility in anti-cancer immunotherapy, including immune checkpoint blockade (ICB), neoantigen-specific T cell receptor-engineered T (TCR-T), chimeric antigen receptor T (CAR-T), and therapeutic cancer vaccines (TCVs). After recognizing presented neoantigens, the immune system becomes activated and triggers the death of tumor cells. Neoantigens may be derived from multiple origins, including somatic mutations (single nucleotide variants, insertion/deletions, and gene fusions), circular RNAs, alternative splicing, RNA editing, and polymorphic microbiome.

The clinical assessment of lung involvement in patients with Still's disease, results from the multicentre international AIDA Network Still's Disease Registry.

Objectives: To assess the lung involvement in patients with Still's disease, an inflammatory disease assessing both children and adults. To exploit possible associated factors for parenchymal lung involvement in these patients.

Methods: A multicentre observational study was arranged assessing consecutive patients with Still's disease characterized by the lung involvement among those included in the AIDA (AutoInflammatory Disease Alliance) Network Still's Disease Registry.

Connecting the dots: Low-grade appendiceal mucinous neoplasms and serrated polyps in the appendix.

Objective: This study aimed to examine the relationship between low-grade appendiceal mucinous neoplasms (LAMNs) and serrated polyps (SPs) of the appendix, both characterized by KRAS mutations and overlapping morphologic features.

Methods: We analyzed 27 cases of LAMN and 24 cases of SP from archival records, reviewed pathology, and performed molecular analysis on select cases. Four cases initially diagnosed as LAMN were excluded for not meeting diagnostic criteria, and 1 SP case was reclassified as LAMN.

Negative prognostic significance of primary cilia and cytoplasmic β-catenin expression in non-small cell lung cancer.

The objective of this study was to investigate the prognostic significance of the frequency of primary cilia (PC) and β-catenin expression in 218 patients (pts) with non-small cell lung cancer (NSCLC), including 125 pts with adenocarcinoma and 93 pts with squamous cell carcinoma. In the whole group of 218 pts with NSCLC, overall survival (OS) was significantly inferior among pts with present PC than without PC (p=0.024) and with higher cytoplasmic β-catenin expression (25-75%) than with lower cytoplasmic β-catenin expression (<25%) (p=0.

Methylation status of selected genes in non-small cell lung carcinoma - current knowledge and future perspectives.

DNA methylation is recognized as an early event in cancer initiation and progression. This review aimed to compare the methylation status of promoter regions in selected genes across different histological subtypes of non-small cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and the rare but highly aggressive large-cell neuroendocrine carcinoma (LCNEC). A comprehensive literature search was conducted in the PubMed database until August 17, 2024, using standardized keywords to identify reports on promoter methylation in NSCLC.

MTHFD2 promotes breast cancer cell proliferation through IFRD1 RNA m6A methylation-mediated HDAC3/p53/mTOR pathway.

MTHFD2 is highly overexpressed in breast cancer tissues, indicating that it might be used as a target in breast cancer treatment. This study aims to determine the role of MTHFD2 in breast cancer cell proliferation and the molecular pathways involved. In order to investigate MTHFD2 gene expression and its downstream pathways in breast cancer, we started our inquiry with a bioinformatics analysis.

Clinical features, treatment modalities, and survival rates of pediatric central nervous system tumors: A retrospective analysis from a single center (2000-2020).

Pediatric central nervous system (CNS) tumors represent 20-25% of childhood malignancies, with 35-40 new cases annually in Slovakia. Despite treatment advances, high mortality and poor quality of life in a lot of cases persist. This study assesses the clinical features, treatment modalities, and survival rates of pediatric CNS tumor patients in the single largest center in Slovakia.

Sesterterpenoids: sources, structural diversity, biological activity, and data management.

Reviewing the literature published up to October 2024.Sesterterpenoids are one of the most chemically diverse and biologically promising subgroup of terpenoids, the largest family of secondary metabolites. The present review article summarizes more than seven decades of studies on isolation and characterization of more than 1600 structurally novel sesterterpenoids, supplemented by biological, pharmacological, ecological, and geographic distribution data.

Maternal Fasting Plasma Glucose Level in Early Gestation and Developmental Delay in 2-year-old Children.

Background: The association of maternal hyperglycemia with childhood developmental delay has been examined; however, only 2 studies used maternal blood glucose level as a continuous variable as an exposure. A present study aimed to investigate the influence of maternal fasting plasma glucose (mFPG) level in early gestation on developmental delay in children.

Methods: This cohort study included 1541 mother-child pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

Epigallocatechin 3-gallate-induced neuroprotection in neurodegenerative diseases: molecular mechanisms and clinical insights.

Neurodegenerative diseases (NDs) are caused by progressive neuronal death and cognitive decline. Epigallocatechin 3-gallate (EGCG) is a polyphenolic molecule in green tea as a neuroprotective agent. This review evaluates the therapeutic effects of EGCG and explores the molecular mechanisms that show its neuroprotective properties.

Circular RNA ATP9A Stimulates Non-small Cell Lung Cancer Progression via MicroRNA-582-3p/Ribosomal Protein Large P0 Axis and Activating Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathway.

Circular RNAs (circRNAs), along with their pathogenic property in non-small cell lung cancer (NSCLC), require comprehensive analyses and explanations. The study is established with the purpose to elucidate the potential molecular mechanism of circATP9A in NSCLC. CircATP9A and microRNA (miR)-582-3p were evaluated by real-time quantitative polymerase chain reaction, and ribosomal protein large P0 (RPLP0), cleaved caspase-3, cleaved Ki-67, epithelial-to-mesenchymal transition (EMT)-associated proteins (N-cadherin and E-cadherin), and core proteins of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were by Western blot.

Wall shear stress modulates metabolic pathways in endothelial cells.

Introduction: Hemodynamic forces play a crucial role in modulating endothelial cell (EC) behavior, significantly influencing blood vessel responses. While traditional in vitro studies often explore ECs under static conditions, ECs are exposed to various hemodynamic forces in vivo. This study investigates how wall shear stress (WSS) influences EC metabolism, focusing on the interplay between WSS and key metabolic pathways.

The potential link between the development of Alzheimer's disease and osteoporosis.

Alzheimer's disease (AD) and osteoporosis (OP) pose distinct but interconnected health challenges, both significantly impacting the aging population. AD, a neurodegenerative disorder characterized by memory impairment and cognitive decline, is primarily associated with the accumulation of abnormally folded amyloid beta (Aβ) peptides and neurofibrillary tangles in the brain. OP, a skeletal disorder marked by low bone mineral density, involves dysregulation of bone remodeling and is associated with an increased risk of fractures.

Time-lapse analysis of embryos classified as euploid, mosaic, and aneuploid after embryonic trophectoderm biopsy.

Purpose: Analyze morphokinetic, morphology, and KIDscore™Day5 in different PGT-A classes, focusing on putative mosaicism level and type.

Methods: The single-center retrospective study analyzed 832 embryoscope-cultured blastocysts from cycles with at least one putative mosaic, conducted from 2020 to 2022. A P-value < 0.

Intracellular concentration of ADA2 is a marker for monocyte differentiation and activation.

Adenosine, a critical molecule regulating cellular function both inside and outside cells, is controlled by two human adenosine deaminases: ADA1 and ADA2. While ADA1 primarily resides in the cytoplasm, ADA2 can be transported to lysosomes within cells or secreted outside the cell. Patients with ADA2 deficiency (DADA2) often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood.

Performance evaluation of the LIOFeron®TB/LTBI IGRA for screening of paediatric LTBI and tuberculosis.

Purpose: High-accuracy diagnostic screening tests for Mycobacterium tuberculosis (MTB) infection are required, primarily to detect patients with latent infections (LTBIs) in order to avoid their progression to active tuberculosis disease. The performance of the novel IGRA LIOFeron®TB/LTBI was evaluated in children. The originality of this test is the new MTB antigen contained (L-alanine dehydrogenase), identified as a tool to differentiate active TB from LTBI infection.

Impact of calreticulin mutations on treatment and survival outcomes in myelofibrosis during ruxolitinib therapy.

Calreticulin (CALR) mutations are detected in around 20% of patients with primary and post-essential thrombocythemia myelofibrosis (MF). Regardless of driver mutations, patients with splenomegaly and symptoms are generally treated with JAK2-inhibitors, most commonly ruxolitinib. Recently, new therapies specifically targeting the CALR mutant clone have entered clinical investigation.

Glucocorticoids Alter Bone Microvascular Barrier via MAPK/Connexin43 Mechanisms.

Glucocorticoids (GCs) are standard-of-care treatments for inflammatory and immune disorders, and their long-term use increases the risk of osteoporosis. Although GCs decrease bone functionality, their role in bone microvasculature is incompletely understood. Herein, the study investigates the mechanisms of bone microvascular barrier function via osteoblast-endothelial interactions in response to GCs.

Androgens differentially modulate glucocorticoid effects on adipose tissue and lean mass.

Glucocorticoids and androgens affect each other in several ways. In metabolic organs such as adipose tissue and the liver, androgens enhance glucocorticoid-induced insulin resistance and promote fat accumulation in male mice. However, the direct contribution of the androgen receptor (AR) to these effects is unknown.