Ammonia and beyond - biomarkers of hepatic encephalopathy.

Ammonia is a product of amino acid metabolism that accumulates in the blood of patients with liver cirrhosis, leading to neurotoxic effects and hepatic encephalopathy (HE). HE manifestations can range from mild, subclinical disturbances in cognition, or minimal HE (mHE) to gross disorientation and coma, a condition referred to as overt HE. Many blood-based biomarkers reflecting these neurotoxic effects of ammonia and liver disease can be measured in the blood allowing the development of new biomarkers to diagnose cirrhosis patients at risk of developing HE.

Pericytes in Glioblastoma: Hidden Regulators of Tumor Vasculature and Therapy Resistance.

Glioblastoma IDH wild type (GB), the most common malignant primary brain tumor, is characterized by rapid proliferation, extensive infiltration into surrounding brain tissue, and significant resistance to current therapies. Median survival is only 15 months despite extensive clinical efforts. The tumor microenvironment (TME) in GB is highly specialized, supporting the tumor's aggressive behavior and its ability to evade conventional treatments.

A systematic review of Aedes aegypti population dynamics models based on differential equations.

The global spread of Aedes aegypti and the associated public health risk have stimulated the development of several mathematical models to predict population dynamics in response to biological or environmental changes in real, future, or simulated scenarios. The aim of this study is to identify published articles on differential equation-based population dynamics models of Aedes aegypti, highlight their differences and commonalities, and examine their application in surveillance and control programs. Following the PRISMA guidelines, a systematic review was conducted in seven electronic databases (Scopus, PUBMED, IEEE Xplore, Science Direct, DOAJ, Scielo, and Google Scholar), with the last update on 8 February 2023.

Neurofilament Light Chain Protein in Plasma and Extracellular Vesicles Is Associated with Minimal Hepatic Encephalopathy and Responses to Rifaximin Treatment in Cirrhotic Patients.

Neurofilament light chain protein (NfL) levels reflect neuronal damage in several neurological diseases and have been proposed as a possible biomarker. Plasma extracellular vesicles (EVs) could play an important role as mediators of the inflammatory changes associated with inducing minimal hepatic encephalopathy (MHE) in cirrhotic patients. This study investigated the association of NfL levels in plasma and EVs with the presence of MHE in cirrhotic patients, and with responses to rifaximin treatment.

Mild Cognitive Impairment Is Associated with Enhanced Activation of Th17 Lymphocytes in Non-Alcoholic Fatty Liver Disease.

Patients with nonalcoholic fatty liver disease (NAFLD) may show mild cognitive impairment (MCI). The mechanisms involved remain unclear. The plasma concentrations of several cytokines and chemokines were measured in 71 NAFLD patients (20 with and 51 without MCI) and 61 controls.

Glucose 6-P Dehydrogenase Overexpression Improves Aging-Induced Endothelial Dysfunction in Aorta from Mice: Role of Arginase II.

The increase of vascular arginase activity during aging causes endothelial dysfunction. This enzyme competes with the endothelial nitric oxide synthase (eNOS) for L-arginine substrate. Our hypothesis is that glucose 6-P dehydrogenase (G6PD) overexpression could improve the endothelial function modulating the arginase pathway in aorta from mice.

Development of an Image-Based Methodology for the Evaluation of Histopathological Features in Human Meningioma.

Meningioma is the most common intracranial tumor in adulthood. With a clear female predominance and a recurrence rate that reaches 20%, it is, despite being considered a benign tumor, a pathology that greatly compromises post-diagnosis quality of life. Its prone to recur or progress to a higher degree is difficult to predict in the absence of obvious histological criteria.

Matched Paired Primary and Recurrent Meningiomas Points to Cell-Death Program Contributions to Genomic and Epigenomic Instability along Tumor Progression.

Meningioma (MN) is an important cause of disability, and predictive tools for estimating the risk of recurrence are still scarce. The need for objective and cost-effective techniques addressed to this purpose is well known. In this study, we present methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as a friendly method for deepening the understanding of the mechanisms underlying meningioma progression.

Desmoplastic infantile astrocytoma with atypical phenotype, PTEN homozygous deletion and BRAF V600E mutation.

Desmoplastic infantile astrocytoma (DIA) is rare, cystic and solid tumor of infants usually found in superficial cerebral hemispheres. Although DIA is usually benign, uncommon cases bearing malignant histological and aggressive clinical features have been described in the literature. We report a newborn patient who was diagnosed with a DIA and died postresection.

Metabolic syndrome is associated with poor response to rifaximin in minimal hepatic encephalopathy.

Patients with cirrhosis may show minimal hepatic encephalopathy (MHE), for which rifaximin is effective. Metabolic syndrome may be associated with cognitive impairment. Our aims were to evaluate the influence of metabolic syndrome features on response to rifaximin for neurological and inflammatory alterations in MHE.

Whole-exome sequencing, amplification and infiltration patterns in human glioblastoma.

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. This cancer shows rapid, highly infiltrative growth, that invades individually or in small groups the surrounding tissue. The aggressive tumor biology of GBM has devastating consequences with a median survival of 15 months.

PPARγ as an indicator of vascular function in an experimental model of metabolic syndrome in rabbits.

Background And Aims: Underlying mechanisms associated with vascular dysfunction in metabolic syndrome (MetS) remain unclear and can even vary from one vascular bed to another.

Methods: In this study, MetS was induced by a high-fat, high-sucrose diet, and after 28 weeks, aorta and renal arteries were removed and used for isometric recording of tension in organ baths, protein expression by Western blot, and histological analysis to assess the presence of atherosclerosis.

Results: MetS induced a mild hypertension, pre-diabetes, central obesity and dyslipidaemia.

Bowel ultrasonography in acute abdomen: beyond acute appendicitis.

Acute abdomen is a common reason for consultation in the emergency department. A broad spectrum of entities, including diverse diseases of the gastrointestinal tract, can cause acute abdomen. Although computed tomography is the technique most widely used to evaluate acute abdomen in the emergency department, abdominal ultrasound is often performed first and allows bowel disease to be suspected.

The Status of Modulates the Effect of miRNA-200c on Expression and Cell Migration in Glioblastoma Cells.

Migration of glioblastoma cells into surrounding tissue is one of the main features that makes this tumor incurable. We evaluated whole-genome miRNA expression profiling associated with different EGFR amplification patterns in 30 cases of primary glioblastoma. From the 64 miRNAs that showed differential expression between tumors with a high level of EGFR amplification and tumors without EGFR amplification, 40% were related with cell migration, being miR-200c the most differentially expressed between these two groups.

Identification of New Genetic Clusters in Glioblastoma Multiforme: Status and Losses Influence Prognosis.

Glioblastoma multiforme (GB) is one of the most aggressive tumors. Despite continuous efforts to improve its clinical management, there is still no strategy to avoid a rapid and fatal outcome. amplification is the most characteristic alteration of these tumors.

Identification of a Novel BRCA1 Alteration in Recurrent Melanocytoma Resulting in Increased Proliferation.

Primary meningeal melanocytomas are rare tumors of the central nervous system. Although they are considered benign neoplasms, some reports describe recurrent rates up to 45%. Little is known about their genetic and epigenetic landscape because of their infrequency.

Discovery of a Covalent Inhibitor of KRAS (AMG 510) for the Treatment of Solid Tumors.

KRAS has emerged as a promising target in the treatment of solid tumors. Covalent inhibitors targeting the mutant cysteine-12 residue have been shown to disrupt signaling by this long-"undruggable" target; however clinically viable inhibitors have yet to be identified. Here, we report efforts to exploit a cryptic pocket (H95/Y96/Q99) we identified in KRAS to identify inhibitors suitable for clinical development.

Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma.

Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration.

The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity.

KRAS is the most frequently mutated oncogene in cancer and encodes a key signalling protein in tumours. The KRAS(G12C) mutant has a cysteine residue that has been exploited to design covalent inhibitors that have promising preclinical activity. Here we optimized a series of inhibitors, using novel binding interactions to markedly enhance their potency and selectivity.

Discovery of -(1-Acryloylazetidin-3-yl)-2-(1-indol-1-yl)acetamides as Covalent Inhibitors of KRAS.

KRAS regulates many cellular processes including proliferation, survival, and differentiation. Point mutants of KRAS have long been known to be molecular drivers of cancer. , which occurs in approximately 14% of lung adenocarcinomas, 3-5% of colorectal cancers, and low levels in other solid tumors, represents an attractive therapeutic target for covalent inhibitors.

Characterization of a new glioblastoma cell line, GB-val4, with unusual TP53 mutation.

A novel cell line derived from a human glioblastoma (GB), named GB-val4, has been established and characterized. GB-val4 cells were hyperdiploid, with many numerical and structural chromosomal rearrangements. The cell line did not show mutations in IDH1/IDH2 genes or EGFR amplification, but it presented two missense mutations in TP53, which imply a very low p53 protein activity within the cell line.

PamCSK, a TLR2 ligand, induces differentiation of glioblastoma stem cells and confers susceptibility to temozolomide.

Glioblastoma multiforme (GBM) is the most aggressive human brain tumor, and GBM stem cells (GSC) may be responsible for its recurrence and therapeutic resistance. Toll-like receptors (TLRs), which recognize multiple ligands (endogenous and pathogen-associated) and trigger the immune response of mature immune cells, are also expressed by hematopoietic stem and progenitor cells, where their activation results in the differentiation of these cells into myeloid cells. Since TLR expression has been recently described in neural cells, including neural stem cells, we studied TLR expression by GSCs and the effect of stimulation by TLR ligands on promoting GSC differentiation into mature GBM cells.

Epigenetic changes underlie the aggressiveness of histologically benign meningiomas that recur.

Meningiomas are the most frequent primary brain tumor. Usually, they are curable by surgery, but even after seemingly complete resection, some low-grade lesions recur. Despite recent improvements, signatures having prognostic value in grade I tumors remain poorly characterized.