Identification of multicohort-based predictive signature for NMIBC recurrence reveals SDCBP as a novel oncogene in bladder cancer.

Background: Despite surgical and intravesical chemotherapy interventions, non-muscle invasive bladder cancer (NMIBC) poses a high risk of recurrence, which significantly impacts patient survival. Traditional clinical characteristics alone are inadequate for accurately assessing the risk of NMIBC recurrence, necessitating the development of novel predictive tools.

Methods: We analyzed microarray data of NMIBC samples obtained from the ArrayExpress and GEO databases.

Temozolomide-Promoted MGMT Transcription Contributes to Chemoresistance by Activating the ERK Signalling Pathway in Malignant Melanoma.

Tumour cells possess a multitude of chemoresistance mechanisms, which could plausibly contribute to the ineffectiveness of chemotherapy. O-methylguanine-DNA methyltransferase (MGMT) is an important effector protein associated with Temozolomide (TMZ) resistance in various tumours. To some extent, the expression level of MGMT determines the sensitivity of cells to TMZ, but the mechanism of its expression regulation has not been fully elucidated.

Developmental and environmental effects on VTC2-dependent leaf ascorbate accumulation and functions.

In nature, environmental conditions strongly fluctuate, frequently subjecting plants to periods of immediate photo-oxidative stress. The small molecule ascorbate allows plants to cope with such stress conditions. Ascorbate scavenges reactive oxygen species and enables the rapid and full induction of photoprotective non-photochemical quenching (NPQ).

Signatures of natural selection may indicate a genetic basis for the beneficial effects of oily fish intake in indigenous people from coastal Ecuador.

Atahualpa is a rural village located in coastal Ecuador, a region that has been inhabited by people as early as 10,000 years ago. The traditional diet of their indigenous inhabitants is rich in oily fish and they have, therefore, served as a model for investigating the beneficial effects of such a diet. However, the genetic background of this population has not been studied.

Trajectories of general and central obesity beyond middle age in relation to late-life cognitive decline and dementia.

Objective: The objective was to evaluate the longitudinal patterns of central and general obesity, identify their genetic and behavioral risk determinants, and investigate the association of distinct obesity trajectories beyond middle age with subsequent cognitive decline and the risk of developing dementia in late life.

Methods: Using a nationally representative, longitudinal, community-based cohort, we examined trajectory patterns of obesity over a 14-year span beyond middle age employing latent mixture modeling. We then evaluated their relationship with subsequent cognitive decline through linear mixed models and with the risk of developing dementia using Cox models, adjusting for confounding variables.

Astaxanthin Alleviates Lung Injury by Regulating Oxidative Stress, Inflammatory Response, P2X7 Receptor, NF-κB, Bcl-2, and Caspase-3 in LPS-Induced Endotoxemia.

Sepsis remains the leading cause of multiple-organ injury due to endotoxemia. Astaxanthin (ASTA), widely used in marine aquaculture, has an extraordinary potential for antioxidant and anti-inflammatory activity. Purinergic receptor (e.

Synthesis and biological investigation of peptidomimetic SARS-CoV-2 main protease inhibitors bearing quinoline-based heterocycles at P.

In the last few years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the cause of a worldwide pandemic, highlighting the need for novel antiviral agents. The main protease (M) of SARS-CoV-2 was immediately identified as a crucial enzyme for viral replication and has been validated as a drug target. Here, we present the design and synthesis of peptidomimetic M covalent inhibitors characterized by quinoline-based P moieties.

Vacuolated Parabasal Cells in Papanicolaou Smears Are Cellular Changes Caused by Human Papillomavirus 16 Infection.

In cervical cancer screening, cytology is used as a triage test to refer high-risk human papillomavirus (HR-HPV)-positive women for colposcopy, but its accuracy is inadequate. The present study aimed to demonstrate that the presence of atypical cells with large vacuoles in the cytoplasm of parabasal cells, referred to as vacuolated parabasal cells (VPCs), which are observed in the Pap smears of HPV-positive women, is associated with specific HPV genotypes. Among 2175 patients, 310 with a single HR-HPV infection and cytological diagnosis of high-grade squamous intraepithelial lesions (HSIL) or atypical squamous cells not excluding HSIL (ASC-H) were included, of which 86 were infected with HPV16.

Regulated microbe vaccines: from concept to (pre-clinical) reduction to practice.

Introduction: Vaccines to prevent important infections involving, e.g. influenza viruses, severe acute respiratory syndrome-causing coronaviruses (e.

Ablation of LRP6 in alpha-smooth muscle actin-expressing cells abrogates lung inflammation and fibrosis upon bleomycin-induced lung injury.

Tissue fibrosis is a progressive pathological process with excessive deposition of extracellular matrix proteins (ECM). Myofibroblasts, identified by alpha-smooth muscle actin (αSMA) expression, play an important role in tissue fibrosis by producing ECM. Here, we found that the Wnt antagonist Dickkopf1 (DKK1) induced gene expressions associated with inflammation and fibrosis in lung fibroblasts.

C9orf72 Alleviates DSS‑Induced Ulcerative Colitis via the cGAS-STING Pathway.

Purpose: C9orf72 deficiency contributes to severe inflammation in mice. Ulcerative colitis (UC) is a chronic inflammatory disorder with the shortage of clinical success. However, whether C9orf72 is involved in the progression of UC is not fully understood.

Inhibition of HMGA2 binding to AT-rich DNA by its negatively charged C-terminus.

The mammalian high mobility group protein AT-hook 2 (HMGA2) is a small DNA-binding protein that specifically targets AT-rich DNA sequences. Structurally, HMGA2 is an intrinsically disordered protein (IDP), comprising three positively charged 'AT-hooks' and a negatively charged C-terminus. HMGA2 can form homodimers through electrostatic interactions between its 'AT-hooks' and C-terminus.

Spindle Cell Sarcoma With Novel JAZF1::NUDT5 Gene Fusion: Report of a Previously Undescribed Neoplasm.

Gene fusions involving JAZF1 are a recurrent event in low grade endometrial stromal sarcoma, and have been more recently described in few instances of endometrial stromal sarcoma-like tumors in the genitourinary tract of men. In this article, we describe a previously unreported spindle cell sarcoma harboring an in-frame JAZF1::NUDT5 gene fusion, arising in the chest wall of a 51-year-old man. The tumor had unique morphologic features resembling both endometrial stromal sarcoma and endometrial stromal sarcoma-like tumors, consisting of a mixture of cytologically bland and pleomorphic spindle cells with brisk mitotic activity, within an alternating myxoid and fibrous stroma.

Glycocalyx disruption, endothelial dysfunction and vascular remodeling as underlying mechanisms and treatment targets of chronic venous disease.

The glycocalyx is an essential structural and functional component of endothelial cells. Extensive hemodynamic changes cause endothelial glycocalyx disruption and vascular dysfunction, leading to multiple arterial and venous disorders. Chronic venous disease (CVD) is a common disorder of the lower extremities with major health and socio-economic implications, but complex pathophysiology.

Novel PDGFRB Gene Fusions in Two Cases of Infantile Myofibromatosis.

Infantile myofibromatosis (IM) comprises a wide clinical spectrum, ranging from solitary or multicentric lesions to generalized life-threatening forms. IM is mostly linked to germline or somatic heterozygous mutations in the PDGFRβ tyrosine kinase, encoded by the PDGFRB gene. Treatments for IM range from wait and see approach to systemic chemotherapy, according to the clinical context.

Investigation into the effect of phenylalanine gating on anaerobic haem breakdown using the energy landscape approach.

We have recently demonstrated a novel anaerobic NADH-dependent haem breakdown reaction, which is carried out by a range of haemoproteins. The Yersinia enterocolitica protein, HemS, is the focus of further research presented in the current paper. Using conventional experimental methods, bioinformatics, and energy landscape theory (ELT), we provide new insight into the mechanism of the novel breakdown process.

Delving Into lncRNA-Mediated Regulation of Autophagy-Associated Signaling Pathways in the Context of Breast Cancer.

Breast cancer is a multifaceted and prevalent malignancy, impacting a considerable proportion of women globally. Numerous signaling pathways intricately regulate cellular functions such as growth, proliferation, and survival. Among the various regulators, lncRNAs have emerged as significant players despite their inability to encode proteins.

Rhabdomyosarcoma With EWSR1::NF2 Gene Fusion: A Case Report Potentially Expanding Its Genetic Spectrum.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, presenting with heterogeneous clinical and molecular subtypes. While gene fusions are predominantly associated with alveolar RMS, spindle cell RMS, especially congenital and intraosseous variants, are also linked to specific gene fusions. Furthermore, recently, FGFR1 kinase-driven RMSs were published.

Multiple Coenurus cerebralis Cysts Detected in a Sheep Brain and Molecular Characterization of the Individual Cysts.

Taenia multiceps is found in canids and in its larval stage is known as Coenurus cerebralis causes coenurosis. The disease has a significant impact on the economic value of sheep and goats. The aim of the current study was to identify multiple cysts in the brain of a sheep displaying common symptoms of C.

Phylogenetic and mutational analysis of bovine leukemia virus (BLV) tax gene in specialized dairy production systems in Antioquia, Colombia.

The bovine leukemia virus (BLV) is a pathogen of high importance for the dairy industry. Currently, twelve genotypes have been described worldwide with different pathogenicity and virulence, so it is critical to evaluate the circulating genotypes in each country/region to associate this information with risk situations. The aim of this work was to perform a phylogenetic and mutational analysis of the BLV tax gene in cows that belong to specialized dairies in the Department of Antioquia, Colombia.

Gut microbiota modulation via fecal microbiota transplantation mitigates hyperoxaluria and calcium oxalate crystal depositions induced by high oxalate diet.

Hyperoxaluria, including primary and secondary hyperoxaluria, is a disorder characterized by increased urinary oxalate excretion and could lead to recurrent calcium oxalate kidney stones, nephrocalcinosis and eventually end stage renal disease. For secondary hyperoxaluria, high dietary oxalate (HDOx) or its precursors intake is a key reason. Recently, accumulated studies highlight the important role of gut microbiota in the regulation of oxalate homeostasis.

Pathogenicity assessment of genetic variants identified in patients with severe hypertriglyceridemia: novel cases of Familial Chylomicronemia Syndrome from the Dyslipidemia Registry of the Spanish Atherosclerosis Society.

Purpose: Genetic testing is required to confirm a diagnosis of familial chylomicronemia syndrome (FCS). We assessed the pathogenicity of variants identified in the FCS canonical genes to diagnose FCS cases.

Methods: 245 patients with severe hypertriglyceridemia underwent next-generation sequencing.

Gestational trophoblastic disease: understanding the molecular mechanisms of placental tumours.

Gestational trophoblastic disease (GTD) describes a group of rare benign and cancerous lesions originating from the trophoblast cells of the placenta. These neoplasms are unconventional entities, being one of the few instances in which cancer develops from the cells of another organism, the foetus. Although this condition was first described over 100 years ago, the specific genetic and non-genetic drivers of this disease remain unknown to this day.

ERMP1 as a newly identified ER stress gatekeeper in chronic kidney disease.

ERMP1 is involved in the Unfolded Protein Response (UPR) pathway in response to endoplasmic reticulum (ER) stress. Given the pivotal role of ER stress in the pathogenesis of acute and chronic kidney diseases, we hypothesized that ERMP1 could be instrumental in the development of renal injury. analysis of RNA sequencing datasets from renal biopsies were exploited to assess the expression of ERMP1 in the kidney under normal or pathological conditions.