Leveraging Epigenetic Alterations in Pancreatic Ductal Adenocarcinoma for Clinical Applications.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by late detection and poor prognosis. Recent research highlights the pivotal role of epigenetic alter- ations in driving PDAC development and progression. These changes, in conjunction with genetic mutations, contribute to the intricate molecular landscape of the disease.

The role of hypoxia/ischemia preconditioning in ischemic stroke.

Ischemic stroke can cause damage to neurons, resulting in neurological dysfunction. The main treatments in the acute phase include intravenous thrombolysis, endovascular stent-assisted vascular thrombectomy and antiplatelet therapy. Due to the limitations of the time window and the risk of early intracranial hemorrhage, finding active treatment plans is crucial for improving therapy.

Classification of Fibro-osseous Tumors in the Craniofacial Bones using DNA Methylation and Copy Number Alterations.

Fibro-osseous tumors of the craniofacial bones are a heterogeneous group of lesions comprising cemento-osseous dysplasia (COD), cemento-ossifying fibroma (COF), juvenile trabecular ossifying fibroma (JTOF), psammomatoid ossifying fibroma (PsOF), fibrous dysplasia (FD), and low-grade osteosarcoma (LGOS) with overlapping clinicopathological features. However, their clinical behavior and treatment differ significantly, underlining the need for accurate diagnosis. Molecular diagnostic markers exist for subsets of these tumors, including GNAS mutations in FD, SATB2 fusions in PsOF, mutations involving the RAS-MAPK signaling pathway in COD, and MDM2 amplification in LGOS.

Spatial Localization of Collagen Hydroxylated Proline Site Variation as an Ancestral Trait in the Breast Cancer Microenvironment.

Collagen stroma interactions within the extracellular microenvironment of breast tissue play a significant role in breast cancer, including risk, progression, and outcomes. Hydroxylation of proline (HYP) is a common post-translational modification directly linked to breast cancer survival and progression. Changes in HYP status lead to alterations in epithelial cell signaling, extracellular matrix remodeling, and immune cell recruitment.

Effects of Methylglyoxal on Intestine and Microbiome Composition in Aged Mice.

Background: Methylglyoxal (MGO), a highly reactive precursor of advanced glycation end products (AGEs), is endogenously produced and prevalent in various ultra-processed foods. MGO has emerged as a significant precursor implicated in the pathogenesis of type 2 diabetes and neurodegenerative diseases. To date, the effects of dietary MGO on the intestine have been limited explored.

Pharmacogenetic Testing in Admixed Populations: Frequency of the AMR PGx Working Group Tier 1 Variant Alleles in Brazilians.

This article examines the frequency distribution of Tier 1 pharmacogenetic variants of the Association for Molecular Pathology Pharmacogenomics Working Group Recommendations in two large (>1.000 individuals) cohorts of the admixed Brazilian population, and in patients from the Brazilian Public Health System enrolled in pharmacogenetic trials. Three Tier 1 variants, all in DPYD, were consistently absent, which may justify their non-inclusion in genotyping panels for Brazilians; 13 variants had frequency < 1.

Automated scoring to assess RAD51-mediated homologous recombination in ovarian patient-derived tumor organoids.

PARP inhibitors (PARPi) have been shown to improve progression-free survival, particularly in homologous recombination deficient (HRD) ovarian cancers. Identifying patients eligible to PARPi is currently based on next-generation sequencing (NGS), but the persistence of genomic scars in tumors after restoration of HR or epigenetic changes can be a limitation. Functional assays could thus be used to improve this profiling and faithfully identify HRD tumors.

IKZF1 promotes pyroptosis and prevents M2 macrophage polarization by inhibiting JAK2/STAT5 pathway in colon cancer.

Pyroptosis and macrophage pro-inflammatory activation play an important role in hepatocellular carcinoma (HCC) progression. However, the specific regulatory mechanisms remain unclear. We identified pyroptosis-related differentially expressed genes (DEGs) based on the GSE4183 and GSE44861 datasets as well as EVenn database.

Melanocortin 5 receptor signaling protects against podocyte injury in proteinuric glomerulopathies.

Melanocortin therapeutics, exemplified by adrenocorticotropic hormone, have a proven steroidogenic-independent anti-proteinuric and glomerular protective effect. The biological functions of melanocortins are mediated by melanocortin receptors (MCR), including MC1R, which recent studies have shown to protect against glomerular disease. However, the role of other MCRs like MC5R is unknown.

Insights into the use of DNA content in head and neck squamous cell carcinoma as a method for patient stratification and targeted therapy: Revisiting old concepts and exploring new possibilities.

Background: This review aimed to emphasize the implications of DNA content in head and neck squamous cell carcinoma (HNSCC), focusing on its predictive value, role in patient stratification, and potential as a therapeutic target for this malignancy.

Methods: A narrative review of the literature was conducted through electronic database searches.

Results: In conventional HNSCC, aneuploid tumors are associated with increased lymph node metastasis, locoregional recurrences, poor response to radiotherapy and chemotherapy, and worse prognosis.

Breast cancer outcomes after skin- and nipple-sparing mastectomy in BRCA pathogenic mutation carriers versus non-BRCA carriers.

Unlabelled: Our previous study on BRCA breast cancer carriers disclosed a high local recurrence (LR) rate in patients who underwent skin sparing (SSM) or nipple sparing mastectomy (NSM) without postoperative radiation therapy (RT), compared to breast conservation surgery or mastectomy with RT. The current study compares the LR rates in BRCA versus non BRCA carriers after SSM/NSM in relation the receipt of RT.

Methods: The study was approved by the institutional ethics committee.

Enhancing public health outcomes with AI-powered clinical surveillance: Precise detection of COVID-19 variants using qPCR and nanopore sequencing.

Background: We aimed to evaluate the efficacy of integrating the Varia5 multiplex assay (qPCR) and whole genome sequencing (WGS) for monitoring SARS-CoV-2, focusing on their overall performance in identifying various virus variants.

Methods: This study included 140 naso-pharyngeal swab samples from individuals with suspected COVID-19. We utilized our self-developed Varia5 multiplex assay, which targets five viral genes linked to COVID-19 mutations, in conjunction with comprehensive genomic analysis performed through whole genome sequencing (WGS) using the Oxford Nanopore system.

H4K12 lactylation-regulated NLRP3 is involved in cigarette smoke-accelerated Alzheimer-like pathology through mTOR-regulated autophagy and activation of microglia.

Cigarette smoke (CS), an indoor environmental pollution, is an environmental risk factor for diverse neurological disorders. However, the neurotoxicological effects and mechanisms of CS on Alzheimer's disease (AD) progression remain unclear. We found that CS accelerated the progression of AD, including increasing β-amyloid (Aβ) plaque deposition and exacerbating cognitive decline.

The chemokine CX3CL1 promotes intraperitoneal tumour growth despite enhanced T-cell recruitment in ovarian cancer.

T-cell recruiting chemokines are required for a successful immune intervention in ovarian cancer, and also for the efficacy of modern anticancer agents such as PARP inhibitors. The chemokine CX3CL1 recruits tumour-suppressive T-cells into solid tumours, but also mediates cell-cell adhesions, e.g.

Rewiring cancer: 3D genome determinants of cancer hallmarks.

In modern cancer biology, Hanahan and Weinberg's classic depiction of the Hallmarks of Cancer serves as a heuristic for understanding malignant phenotypes [1]. Genetic determinants of these phenotypes promote cancer induction and progression, and these mutations drive current approaches to understanding and treating cancer. Meanwhile, for over a century, pathologists have noted that profound alterations of nuclear structure accompany transformation, integrating these changes into diagnostic classifications (Figure 1).

Mild behavioral impairment and its relation to amyloid load in isolated REM sleep behavior disorder.

Introduction: In isolated REM sleep behavior disorder (iRBD), the evidence of cognitive impairment and co-existing amyloid pathology suggests that mild behavioral impairment (MBI) may be associated with disease progression. In this study, we investigated MBI and its association with cognitive function, brain amyloid load and glucose metabolism in iRBD patients to evaluate the utility of MBI as a predictive marker of disease progression.

Methods: Patients with iRBD underwent a neuropsychological evaluation, F-florbetaben (FBB) PET, and F-fluorodeoxyglucose (FDG) PET.

The Hao-Fountain syndrome protein USP7 regulates neuronal connectivity in the brain via a novel p53-independent ubiquitin signaling pathway.

Mutation or deletion of the deubiquitinase USP7 causes Hao-Fountain syndrome (HAFOUS), which is characterized by speech delay, intellectual disability, and aggressive behavior and highlights important unknown roles of USP7 in the nervous system. Here, we conditionally delete USP7 in glutamatergic neurons in the mouse forebrain, triggering disease-relevant phenotypes, including sensorimotor deficits, impaired cognition, and aggressive behavior. Although USP7 deletion induces p53-dependent neuronal apoptosis, most behavioral abnormalities in USP7 conditional knockout mice persist following p53 loss.

Protocol for extraction of gut interstitial fluid in mice with two-front nutrient supply.

The intestine features a two-front nutrient supply environment, comprising an enteral side enriched with microbial and dietary metabolites and a serosal side supplied by systemic nutrients, collectively supporting intestinal and systemic homeostasis, but there is currently no optimal approach for extracting and assessing the local intestinal microenvironment. Here, we present a protocol for constructing a nutrient supply model in mice and extracting gut interstitial fluid (GIF) via centrifugation. This model and the extracted GIF are suitable for downstream analyses.

Targeting the IKZF1/BCL-2 axis as a novel therapeutic strategy for treating acute T-cell lymphoblastic leukemia.

Objectives: Acute T-cell lymphoblastic leukemia (T-ALL) is a severe hematologic malignancy with limited treatment options and poor long-term survival. This study explores the role of IKZF1 in regulating BCL-2 expression in T-ALL.

Methods: CUT&Tag and CUT&Run assays were employed to assess IKZF1 binding to the BCL-2 promoter.

Depression and Anxiety Disorders among Persons with Type 2 Diabetes Mellitus in a Tertiary Hospital in Zaria, Nigeria.

Background: Depression and anxiety disorders frequently co-occur with Type 2 Diabetes Mellitus, leading to poor glycaemic control and quality of life through complex biopsychosocial mechanisms. A dual diagnosis of chronic medical and mental health conditions reduces the probability of early recognition and intervention for either. This study was aimed at assessing the prevalence and correlates of depression and anxiety disorders among persons with Type 2 Diabetes Mellitus in a tertiary hospital in North-West Nigeria.

Pituitary adenomas: biology, nomenclature and clinical classification.

An 'adenoma' is a benign neoplasm composed of epithelial tissue, and has been standard nomenclature for primary pituitary neoplasms. In 2022, the fifth edition of the WHO Classification of Endocrine Tumours and of Central Nervous System Tumours, renamed pituitary adenomas as neuroendocrine tumours (NETs), assigning an oncology label to pituitary invariably benign neoplasms. Multidisciplinary workshops convened by the Pituitary Society have questioned the process, validity, and merit of this arbitrary change, while addressing the adverse clinical implications of the proposed new nomenclature.

Quantifying natural amyloid plaque accumulation in the continuum of Alzheimer's disease using ADNI.

Brain amyloid beta neuritic plaque accumulation is associated with an increased risk of progression to Alzheimer's disease (AD) [Pfeil, J., et al. in Neurobiol Aging 106: 119-129, 2021].