Regulatory polymorphisms of , , and genes affect survival of patients with immunotherapy-treated lung cancer.

Background: Immune checkpoint inhibitors (ICI) improved survival of patients with non-small cell lung cancer (NSCLC), yet many patients do not respond to treatment. The identification of markers for ICI response remains an unmet clinical need. This study hypothesizes that host genetics influences the response to ICI, contributing to the variability in efficacy among individuals.

Lipidome profile of Cystic Fibrosis Related Diabetes, Type 1 and Type 2 Diabetes Mellitus: potential links to inflammation and glucose and lipid metabolism.

Cystic Fibrosis (CF) is a genetic disease that primarily affects the pancreas and lungs. CF dyslipidaemia is characterized by decreased circulating lipids and increased ectopic lipid deposition in liver, pancreas, and lungs. Pancreatic exocrine insufficiency precedes the onset of CF related diabetes (CFRD).

PFOA biomonitoring and kidney cancer risk: a meta-analysis of serum levels.

Introduction: The potential link between perfluorooctanoic acid (PFOA) exposure and kidney cancer risk in humans remains uncertain. This meta-analysis aims to clarify the association by analyzing serum PFOA levels, a direct biomarker of internal exposure, rather than relying on indirect environmental or occupational measures.

Methods: A systematic literature search was conducted using PubMed and Web of Science to identify relevant studies.

Modulating the serine metabolism in human differentiated astrocytes: an integrated multi omics approach.

Introduction: Astrocytes are the major source of L-serine (L-Ser) in the brain: the glycolytic intermediate D-3-phosphoglycerate is converted into L-Ser through the phosphorylated pathway (PP) made up of three enzymes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase (PSAT) and phosphoserine phosphatase (PSP), recently proposed to generate a metabolic assembly named serinosome. In the central nervous system, L-Ser is used for a number of functions, including the synthesis of glycine (Gly) and D-serine (D-Ser), the two key NMDAR co-agonists.

Methods: Here, we used iPSC-derived human astrocytes as a cellular model to evaluate the impact on cell metabolism of the overexpression of each of the three enzymes of the PP as GFP-tagged proteins.

Unlocking the African bioeconomy and strengthening biodiversity conservation through genomics and bioinformatics.

The African BioGenome Project (AfricaBP) is a Pan-African initiative aimed at improving food systems and biodiversity conservation through genomics while ensuring equitable data sharing and benefits. The Open Institute is the knowledge exchange platform of the AfricaBP, which aims to bridge local knowledge gaps in biodiversity genomics and bioinformatics and enable infrastructural developments. In 2024, the AfricaBP Open Institute advanced this mission by organizing 31 workshops that attracted more than 3500 registered attendees across 50 African countries, provided training to 401 African researchers in genomics, bioinformatics, molecular biology, sample collections and biobanking, and ethical considerations, across all five African geographical regions involving 40 African and non-African organizations.

Alzheimer's Disease Etiology Hypotheses and Therapeutic Strategies: A Perspective.

Alzheimer's disease (AD) is a progressive, complex, multifactorial, neurodegenerative disease and accounts for most cases of dementia. The currently approved therapy includes cholinesterase inhibitors, NMDA-receptor antagonists and monoclonal antibodies. However, these medications were gradually discovered to be ineffective in removing the root of AD pathogenesis, having only symptomatic effects.

CSPG4.CAR-T Cells Modulate Extracellular Matrix Remodeling in DMD Cardiomyopathy.

Targeting fibrosis in Duchenne muscular dystrophy (DMD)-associated cardiomyopathy is a critical outstanding clinical issue, as cardiac failure remains a leading cause of death despite advances in supportive care. This study evaluates the therapeutic efficacy of CSPG4-targeted chimeric antigen receptor (CAR) T cells in reducing cardiac fibrosis and improving heart function in a preclinical model of the disease. DMD is a progressive genetic disorder characterized by degeneration of skeletal and cardiac muscle.

Spatiotemporal liver dynamics shape hepatocellular heterogeneity and impact in vivo gene engineering.

Background & Aims: Hepatocytes are the liver's main functional cells and are key targets for in vivo gene therapy to treat monogenic diseases. Integrating the transgene into the genome is critical for long-term expression from a single early-life dose, which is achievable via integrating vectors or genome editing. To ensure persistence through liver growth and cell turnover, it is also necessary to target the hepatocytes driving these processes.

A cross-talk established by tumor-targeted cytokines rescues CAR T cell activity and engages host T cells against glioblastoma in mice.

Chimeric antigen receptor (CAR) T cells have shown limited efficacy against solid tumors because of poor tissue penetration, constrained activity, and early exhaustion due to the immunosuppressive tumor microenvironment (TME). Although stimulatory cytokines can counteract immune suppression, their systemic administration entails risk of toxicities and counter-regulatory responses. Here, we leveraged a population of tumor-associated TIE2-expressing macrophages (TEMs) to release interferon-α (IFN-α) and/or orthogonal interleukin-2 (oIL2) at the tumor site.

Imbalanced TGFβ signalling and autophagy drive erythroid priming of hematopoietic stem cells in β-thalassemia.

The hematopoietic stem cell and multipotent progenitor (HSC/MPP) pool dynamically responds to stress to adapt blood output to specific physiological demands. In β-thalassemia (Bthal), severe anemia and ineffective erythropoiesis generate expansion of erythroid precursors and a chronic stress status in the bone marrow (BM) microenvironment. However, the response to the BM altered status at the level of the HSC/MPP compartment in terms of lineage commitment has not been investigated.

Generation and characterization of human iPSC lines from two patients with therapy-resistant epilepsy carrying nonsense heterozygous variants in the SMC1A gene.

Different SMC1A variants contribute to a spectrum of phenotypes. Missense or small in-frame deletions are associated with Cornelia de Lange syndrome (CdLS) while SMC1A truncation variants have been detected in subjects with a clinical phenotype different from CdLS, with moderate-to-severe intellectual disability (ID) and pharmaco-resistant epilepsy. We generated two human iPSC lines from two patients with pharmaco-resistant epilepsy carrying nonsense heterozygous c.

Clinical evaluation of freeze-dried secretome (lyosecretome) for osteoarthritis: a controlled trial in dogs and preliminary safety assessment in horses.

Most in vivo studies on MSC-secretome for osteoarthritis (OA) have relied on animal models, using products lacking pharmaceutical quality, not formulated for clinical use, and insufficiently characterized, limiting knowledge of its effectiveness. This study reports veterinary clinical trials on dogs and horses with spontaneous OA: in dogs (26 subjects), the trial is randomized, double-blinded, and controlled; in horses, 5 clinical cases were treated for safety assessment. Treatment consisted of hyaluronic acid with either lyosecretome - a freeze-dried, injectable MSC-secretome obtained through standardized GMP manufacturing - or mannitol, the lyosecretome excipient (control), intrarticularly administered.

NET Proteomic Profiling Reveals New Pathways Potentially Implicated in Dendritic Cell-Mediated Inflammation in DADA2 Patients.

Purpose: Adenosine deaminase 2 Deficiency (DADA2) is an autoinflammatory disease characterized by systemic vasculopathy, strokes and mild immunodeficiency. Recently NETosis has been implicated in the pathogenesis of Deficiency of Adenosine Deaminase 2. To deep investigate the possible effects of NETs on the immune system we characterized proteomic profile of NETs from DADA2 as compared to HD and Polyarteritis Nodosa (PAN) patients.

Senescence and inflammation are unintended adverse consequences of CRISPR-Cas9/AAV6-mediated gene editing in hematopoietic stem cells.

Gene editing (GE) using homology-directed repair (HDR) in hematopoietic stem and progenitor cells (HSPCs) offers promise for long-range gene correction of inherited genetic disorders. However, cellular responses induced by CRISPR-Cas9/AAV6 engineering impair the long-term repopulating potential of HDR-edited HSPCs, adversely impacting the safety and efficacy of clinical translation. Our study uncovers a durable senescence-like response in genetically engineered HSPCs triggered by p53 and interleukin (IL)-1/nuclear factor κB (NF-κB) activation, which restricts graft size and clonal diversity in long-term transplantation assays.

Modeling breast cancer dynamics through modulable small Vessel Environment Bioreactor (sVEB).

The development of advanced in vitro systems to replicate vascularized tissue environments is critical for studying cancer progression, immune interactions, and therapeutic responses. Traditional models often lack physiological perfusion, scale flexibility, and compatibility with complex microenvironments, limiting their translational impact. The small Vessel Environment Bioreactor (sVEB) represents a promising advancement in microfluidic and organ-on-chip technologies, enabling the replication of dynamic environments that mimic key features of vascular and tumor biology.

GBRAP: A Comprehensive Database and Tool for Exploring Genomic Diversity Across All Domains of Life.

Evolutionary studies require extensive examination of genomic information across all domains of life. Despite the availability of a large number of genomes through GenBank, the effective visualization or comparison of the information they contain is challenging due to many reasons, including their size. We introduce genome-based retrieval and analysis parser, a comprehensive software tool to analyze genome files, and an online database housing an extensive collection of carefully curated, high-quality genome statistics for all the organisms available in the RefSeq database of National Center for Biotechnology Information.

Genome-wide association study of long COVID.

Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can result in long coronavirus disease (COVID), typically manifesting as fatigue, pulmonary symptoms and cognitive dysfunction. The biological mechanisms behind long COVID remain unclear.

Characterization and Clinical Implications of p53 Dysfunction in Patients With Myelodysplastic Syndromes.

Purpose: Tumor Protein 53 (p53) expressed from gene is a seminal tumor suppressor. We aimed to characterize mutational and nonmutational mechanisms of p53 dysfunction in myelodysplastic syndromes (MDS) and to investigate their clinical effect.

Patients And Methods: We analyzed a cohort of 6,204 patients with MDS and subsets of patients with available information on RNA sequencing of tumor cells (n = 109), high-dimensional phenotype of immune cells (n = 77), and multiomics analysis (RNA sequencing and proteomics) on single cells (n = 15).

Deciphering the landscape of allosteric glutaminase 1 inhibitors as anticancer agents.

Glutamine is the second most utilised energy source after glucose for cancer cells to support their proliferation and survival. Glutaminase 1 (GLS1) is the rate-limiting enzyme during the glutaminolysis pathway and thus represents a promising therapeutic target for the development of innovative antitumor agents. Two main classes of GLS1 inhibitors, based on their different binding mode, are reported: the substrate active site and the allosteric site inhibitors.

Mechanisms of hematopoietic clonal dominance in VEXAS syndrome.

Clonal dominance characterizes hematopoiesis during aging and increases susceptibility to blood cancers and common nonmalignant disorders. VEXAS syndrome is a recently discovered, adult-onset, autoinflammatory disease burdened by a high mortality rate and caused by dominant hematopoietic clones bearing somatic mutations in the UBA1 gene. However, pathogenic mechanisms driving clonal dominance are unknown.

CoPPIs algorithm: a tool to unravel protein cooperative strategies in pathophysiological conditions.

We present here the co-expressed protein-protein interactions algorithm. In addition to minimizing correlation-causality imbalance and contextualizing protein-protein interactions to the investigated systems, it combines protein-protein interactions and protein co-expression networks to identify differentially correlated functional modules. To test the algorithm, we processed a set of proteomic profiles from different brain regions of controls and subjects affected by idiopathic Parkinson's disease or carrying a GBA1 mutation.

Lamin A/C regulates cerebellar granule cell maturation.

Lamin A/C is a nuclear type V intermediate filament protein part of the meshwork structure underlying the inner nuclear membrane (nuclear lamina), which plays numerous roles, including maintenance of nuclear shape, heterochromatin organization, and transcriptional regulation. Our group has demonstrated the role of Lamin A/C in different pathophysiological conditions. Here, we investigated for the first time how Lamin A/C affects neuronal maturation in rat cerebellar granule cells (GCs).

Exploring the complex population structure and admixture of four local Hungarian sheep breeds.

The origin of sheep and their spread following domestication have been widely investigated using archaeology, genetics, and genomics. A thorough investigation of the genetic diversity of the breeds is key to providing useful information for conservation and breeding programmes. In Hungary, sheep farming contributes to the agricultural sector and national economy.

Glycosylation Regulation by TMEM230 in Aging and Autoimmunity.

Aging is often a choice between developing cancer or autoimmune disorders, often due in part to loss of self-tolerance or loss of immunological recognition of rogue-acting tumor cells. Self-tolerance and cell recognition by the immune system are processes very much dependent on the specific signatures of glycans and glycosylated factors present on the cell plasma membrane or in the stromal components of tissue. Glycosylated factors are generated in nearly innumerable variations in nature, allowing for the immensely diverse role of these factors in aging and flexibility necessary for cellular interactions in tissue functionality.

Uncovering New Biomarkers for Prostate Cancer Through Proteomic and Network Analysis.

Background: Prostate cancer (PCa), is the second most prevalent solid tumor among men worldwide (7.3%), and the leading non-skin cancer in USA where it represents 14.9% of all new cancer cases diagnosed in 2024.