Natural Product Identification and Molecular Docking Studies of Leishmania Major Pteridine Reductase Inhibitors.

: Pteridine reductase 1 (PTR1) has been one of the prime targets for discovering novel antileishmanial therapeutics in the fight against Leishmaniasis. This enzyme catalyzes the NADPH-dependent reduction of pterins to their tetrahydro forms. While chemotherapy remains the primary treatment, its effectiveness is constrained by drug resistance, unfavorable side effects, and substantial associated costs.

Molecular Epidemiology, Drug-Resistant Variants, and Therapeutic Implications of Hepatitis B Virus and Hepatitis D Virus Prevalence in Nigeria: A National Study.

Information on circulating HBV (sub-)genotype, variants, and hepatitis D virus (HDV) coinfection, which vary by geographical area, is crucial for the efficient control and management of HBV. We investigated the genomic characteristics of HBV (with a prevalence of 8.1%) and the prevalence of HDV in Nigeria.

Assessment of Antibiotic Resistance Among Isolates of spp. and spp. in Wildlife and Their Environment from Portugal: A Positive Epidemiologic Outcome.

One of the significant challenges facing modern medicine is the rising rate of antibiotic resistance, which impacts public health, animal health, and environmental preservation. Evaluating antibiotic resistance in wildlife and their environments is crucial, as it offers essential insights into the dynamics of resistance patterns and promotes strategies for monitoring, prevention, and intervention. and genera isolates were recovered from fecal samples of wild animals and environmental samples using media without antibiotic supplementation.

Clinical Characteristics, Laboratory Parameters, and Molecular Epidemiology of Neuroinvasive Flavivirus Infections in a Hotspot Region of Eastern Croatia.

Neuroinvasive flaviviruses such as tick-borne encephalitis virus (TBEV) and West Nile virus (WNV) are widely distributed in continental Croatian regions. We analyzed clinical characteristics, laboratory parameters, and molecular epidemiology of neuroinvasive flavivirus infections in eastern Croatia. A total of 43 patients with confirmed flavivirus infection hospitalized from 2017 to 2023 were included in the study.

The General Principle of the Warburg Effect as a Possible Approach for Cancer Immunotherapy: The Regulatory Effect of Plant Extracts Could Change the Game.

The interpretation of the biochemistry of immune metabolism could be considered an attractive scientific field of biomedicine research. In this review, the role of glycolysis in macrophage polarization is discussed together with mitochondrial metabolism in cancer cells. In the first part, the focus is on the Warburg effect and redox metabolism during macrophage polarization, cancer development, and management of the immune response by the cancer cells.

Post-Translational Modifications of Proteins Orchestrate All Hallmarks of Cancer.

Post-translational modifications (PTMs) of proteins dynamically build the buffering and adapting interface between oncogenic mutations and environmental stressors, on the one hand, and cancer cell structure, functioning, and behavior. Aberrant PTMs can be considered as enabling characteristics of cancer as long as they orchestrate all malignant modifications and variability in the proteome of cancer cells, cancer-associated cells, and tumor microenvironment (TME). On the other hand, PTMs of proteins can enhance anticancer mechanisms in the tumoral ecosystem or sustain the beneficial effects of oncologic therapies through degradation or inactivation of carcinogenic proteins or/and activation of tumor-suppressor proteins.

Alcohol Consumption and Autoimmune Diseases.

Alcohol is the second-most misused substance after tobacco. It has been identified as a causal factor in more than 200 diseases and 5.3% of all deaths and is associated with significant behavioral, social, and economic difficulties.

The Role of Nutrition, Oxidative Stress, and Trace Elements in the Pathophysiology of Autism Spectrum Disorders.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction, alongside repetitive behaviors, and atypical sensory-motor patterns. The growing prevalence of ASD has driven substantial advancements in research aimed at understanding its etiology, preventing its onset, and mitigating its impact. This ongoing effort necessitates continuous updates to the body of knowledge and the identification of previously unexplored factors.

HERC1 E3 Ubiquitin Ligase Is Necessary for Autophagy Processes and for the Maintenance and Homeostasis of Vesicles in Motor Nerve Terminals, but Not for Proteasomal Activity.

The ubiquitin proteasome system (UPS) is implicated in protein homeostasis. One of the proteins involved in this system is HERC1 E3 ubiquitin ligase, which was associated with several processes including the normal development and neurotransmission at the neuromuscular junction (NMJ), autophagy in projection neurons, myelination of the peripheral nervous system, among others. The tambaleante (tbl) mouse model carries the spontaneous mutation Gly483Glu substitution in the HERC1 E3 protein.

A Senescent Cluster in Aged Human Hematopoietic Stem Cell Compartment as Target for Senotherapy.

To identify the differences between aged and young human hematopoiesis, we performed a direct comparison of aged and young human hematopoietic stem and progenitor cells (HSPCs). Alterations in transcriptome profiles upon aging between humans and mice were then compared. Human specimens consist of CD34+ cells from bone marrow, and mouse specimens of hematopoietic stem cells (HSCs; Lin- Kit+ Sca1+ CD150+).

Fecal Microbiota Strongly Correlates with Tissue Microbiota Composition in Colorectal Cancer but Not in Non-Small Cell Lung Cancer.

Microbiota could be of interest in the diagnosis of colorectal and non-small cell lung cancer (CRC and NSCLC). However, how the microbial components of tissues and feces reflect each other remains unknown. In this work, our main objective is to discover the degree of correlation between the composition of the tissue microbiota and that of the feces of patients affected by CRC and NSCLC.

Charge Reversal of the Uppermost Arginine in Sliding Helix S4-I Affects Gating of Cardiac Sodium Channel.

Several mutations of the uppermost arginine, R219, in the voltage-sensing sliding helix S4 of cardiac sodium channel Nav1.5 are reported in the ClinVar databases, but the clinical significance of the respective variants is unknown (VUSs). AlphaFold 3 models predicted a significant downshift of S4 in the R219C VUS.

Clinical and Genomic Features of Androgen Indifferent Prostate Cancer.

Androgen-indifferent prostate cancer (AIPC) is increasingly common and particularly lethal. Data describing these tumors are sparse, and AIPC remains a poorly understood malignancy. Utilizing the Oncology Research Information Exchange Network (ORIEN) database, we enriched for tumors with features of AIPC using previously described characteristics.

Molecular Mechanisms of Dietary Compounds in Cancer Stem Cells from Solid Tumors: Insights into Colorectal, Breast, and Prostate Cancer.

Cancer stem cells (CSC) are known to be the main source of tumor relapse, metastasis, or multidrug resistance and the mechanisms to counteract or eradicate them and their activity remain elusive. There are different hypotheses that claim that the origin of CSC might be in regular stem cells (SC) and, due to accumulation of mutations, these normal cells become malignant, or the source of CSC might be in any malignant cell that, under certain environmental circumstances, acquires all the qualities to become CSC. Multiple studies indicate that lifestyle and diet might represent a source of wellbeing that can prevent and ameliorate the malignant phenotype of CSC.

Circulating Tumor Cell-Free DNA as Prognostic Biomarker in Non-Small Cell Lung Cancer Patients Undergoing Immunotherapy: The CORELAB Experience.

The expression level of Programmed Death-Ligand 1 (PD-L1) determined by the immunohistochemical method is currently approved to test the potential efficacy of immune-checkpoint inhibitors and to candidate patients with Non-Small Cell Lung Cancer (NSCLC) for treatment with immunotherapeutic drugs. As part of the CORELAB (New prediCtivebiOmaRkers of activity and Efficacy of immune checkpoint inhibitors in advanced non-small cell Lung cArcinoma) project, aimed at identifying new predictive and prognostic biomarkers in NSCLC patients receiving immunotherapeutic drugs, we investigated the role of circulating tumor DNA (ctDNA) molecular characterization as an additional predictive biomarker. We analyzed plasma ctDNA by targeted Next Generation Sequencing in a subset of 50 patients at different time points.

Exploring the Pharmacogenomic Map of Croatia: PGx Clustering of 522-Patient Cohort Based on UMAP + HDBSCAN Algorithm.

Pharmacogenetics is a branch of genomic medicine aiming to personalize drug prescription guidelines based on individual genetic information. This concept might lead to a reduction in adverse drug reactions, which place a heavy burden on individual patients' health and the economy of the healthcare system. The aim of this study was to present insights gained from the pharmacogenetics-based clustering of over 500 patients from the Croatian population.

The Modulatory Effect of Selol (Se IV) on Pro-Inflammatory Pathways in RAW 264.7 Macrophages.

Selol is a semi-synthetic mixture of selenized triglycerides. The results of biological studies revealed that Selol exhibits several anticancer effects. However, studies on its potential anti-inflammatory activity are scarce, and underlying signaling pathways are unknown.

Molecular Epidemiology and In-Depth Characterization of Clinical Isolates from Armenia.

The global dissemination of pathotypes with multidrug-resistant (MDR) and hypervirulent traits poses a threat to public health. The situation in Armenia is unclear, and we performed a comprehensive characterisation of 48 clinical isolates of , collected from 2018 to 2024. The majority of the isolates (64.

AdipoRon's Impact on Alzheimer's Disease-A Systematic Review and Meta-Analysis.

Alzheimer's disease (AD) remains a leading cause of cognitive decline and mortality worldwide, characterized by neurodegeneration, synaptic deficiencies, and neuroinflammation. Despite advancements in early detection, diagnosis, and treatment, AD presents substantial challenges due to its complex pathology, heterogeneity, and the limited efficacy of current therapies. Consequently, there is a pressing need for novel therapeutic agents to target the multifaceted aspects of AD pathology, enhance current treatments, and minimize adverse effects.

A Multi-Omics Analysis of a Mitophagy-Related Signature in Pan-Cancer.

Mitophagy, an essential process within cellular autophagy, has a critical role in regulating key cellular functions such as reproduction, metabolism, and apoptosis. Its involvement in tumor development is complex and influenced by the cellular environment. Here, we conduct a comprehensive analysis of a mitophagy-related gene signature, composed of , , , , , , and , across various cancer types, revealing significant differential expression patterns associated with molecular subtypes, stages, and patient outcomes.

Unraveling the Beneficial Role of Resveratrol in Fructose-Induced Non-Alcoholic Steatohepatitis with a Focus on the AMPK/Nrf2 Signaling Axis.

: High fructose intake is associated with non-alcoholic fatty liver disease (NAFLD), a chronic liver disease that is on the rise worldwide. New alternatives for treatment, such as bioactive phytochemicals, are needed. The aim of this study was to investigate the beneficial role of resveratrol in treating non-alcoholic steatohepatitis (NASH).

The Structural, Biophysical, and Antigenic Characterization of the Goose Parvovirus Capsid.

Goose parvovirus (GPV) is an etiological agent of Derzsy's disease, afflicting geese and Muscovy ducks worldwide. Its high mortality rate among goslings and ducklings causes large losses to the waterfowl industry. Toward molecular and structural characterization, virus-like particles (VLPs) of GPV were produced, and the capsid structure was determined by cryogenic electron microscopy (cryo-EM) at a resolution of 2.

Studying the Oncolytic Activity of Strains Against Hepatoma, Glioma, and Pancreatic Cancer and .

Background: Cancer remains a leading cause of mortality globally. Conventional treatment modalities, including radiation and chemotherapy, often fall short of achieving complete remission, highlighting the critical need for novel therapeutic strategies. One promising approach involves the oncolytic potential of Group A (GAS) strains for tumor treatment.

Atypical Leber Hereditary Optic Neuropathy (LHON) Associated with a Novel MT-CYB:m.15309T>C(Ile188Thr) Variant.

The study presents a detailed examination and follow-up of a Slovenian patient with an Leber Hereditary Optic Neuropathy (LHON)-like phenotype and bilateral optic neuropathy in whom genetic analysis identified a novel variant :m.15309T>C (Ile188Thr). We provide detailed analysis of the clinical examinations of a male patient with bilateral optic neuropathy from the acute stage to 8 years of follow-up.

Oxidative-Stress-Mediated Epigenetic Dysregulation in Spermatogenesis: Implications for Male Infertility and Offspring Health.

Male reproductive health is governed by an intricate interplay of genetic, epigenetic, and environmental factors. Epigenetic mechanisms-encompassing DNA methylation, histone modifications, and non-coding RNA activity-are crucial both for spermatogenesis and sperm maturation. However, oxidative stress, driven by excessive reactive oxygen species, disrupts these processes, leading to impaired sperm function and male infertility.