FGF21 and APOA1 mRNA-based therapies for the treatment of experimental acute pancreatitis.

Background: Acute pancreatitis (AP) presents a significant clinical challenge with limited therapeutic options. The complex etiology and pathophysiology of AP emphasize the need for innovative treatments. This study explores mRNA-based therapies delivering fibroblast growth factor 21 (FGF21) and apolipoprotein A1 (APOA1), alone and in combination, for treating experimental AP.

Proteomics and recurrence of atrial fibrillation: a pilot study nested in the PREDIMAR trial.

Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide. Although catheter ablation is the most efficacious therapy, relapses occur frequently (30%) in the first year after ablation. Novel biomarkers of recurrence are needed for a better prediction of recurrence and management of AF.

Characteristics of snakebite patients due to Naja samarensis in the Philippines: a prospective hospital-based study.

Background: Little is known about snakebites by Naja samarensis, a species unique to the Philippines. The aim here is to describe the clinical and epidemiological characteristics of patients bitten by this medically important cobra in the Eastern Visayas.

Methods: A hospital-based prospective study analysed the features of snakebite patients attending Eastern Visayas Medical Center between June 2022 and May 2023.

In-depth mass-spectrometry reveals phospho-RAB12 as a blood biomarker of G2019S LRRK2-driven Parkinson's disease.

Leucine-rich repeat kinase 2 (LRRK2) inhibition is a promising disease-modifying therapy for LRRK2-associated Parkinson's disease (L2PD) and idiopathic PD (iPD). However, pharmaco-dynamic readouts and progression biomarkers for clinical trials aiming for disease modification are insufficient since no endogenous marker reflecting enhanced kinase activity of the most common LRRK2 G2019S mutation has been reported yet in L2PD patients. Employing phospho-/proteomic analyses we assessed the impact that LRRK2 activating mutations had in peripheral blood mononuclear cells (PBMCs) from a LRRK2 clinical cohort from Spain (n=174).

Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes.

Schizophrenia is a complex multifactorial disorder and increasing evidence suggests the involvement of immune dysregulations in its pathogenesis. We observed that IKZF1 and IKZF2, classic immune-related transcription factors (TFs), were both downregulated in patients' peripheral blood mononuclear cells (PBMCs) but not in their brain. We generated a new mutant mouse model with a reduction in Ikzf1 and Ikzf2 to study the impact of those changes.

From geriatric assessment to inflammation. A pilot, observational, study about frailty components in older patients with persistent atrial fibrillation.

Background: Atrial fibrillation (AF) is the most common arrhythmia diagnosed at an older age. AF is associated with frailty, a condition possibly justifying the higher rate of complications and mortality in aged individuals. This study was aimed at describing the characteristics correlated to frailty in older AF subjects.

DSTYK Inhibition Sensitizes NSCLC to Taxane-Based Chemotherapy.

Introduction: Chemotherapy continues to be the standard treatment for patients noneligible for targeted or immune-based therapies; nevertheless, treatment resistance remains a major clinical challenge. We previously found that expression levels of DSTYK, a poorly explored dual serine/threonine and tyrosine kinase frequently amplified in cancer, identified patients with lung cancer exhibiting poor response to immune checkpoint inhibitors, and found that its inhibition sensitizes to immunotherapy. Seeking to explore the potential of DSTYK targeting in additional indications, we investigated the functional relevance and actionability of DSTYK in lung cancer chemoresistance.

Chaetotaxy of the fourth larval stage of Pintomyia longiflocosa, a primary vector of cutaneous leishmaniasis in Colombia.

Introduction: Pintomyia (Pifanomyia) longiflocosa is an endemic species from Colombia, found between the central and eastern Andes, and reported as one of the primary vectors of cutaneous leishmaniasis in coffee-growing zones of the country. This species is classified in the Townsendi series and can only be identified by the morphology of the male adults.

Objective: To determine the potential use of the fourth larval stage of the vector Pi.

Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis.

Astrocytes are considered an essential source of blood-borne glucose or its metabolites to neurons. Nonetheless, the necessity of the main astrocyte glucose transporter, i.e.

The role of C-reactive protein as a risk marker of postoperative delirium in older hip fracture patients: a prospective cohort study.

Purpose: Postoperative delirium (POD) is a common and serious neuropsychiatric syndrome that leads to higher morbidity and mortality. We investigated the association between serum C-reactive protein (CRP) and the occurrence of POD in older hip fracture patients, and whether CRP predicted POD better than a clinical model.

Methods: Patients aged ≥ 75 years admitted for surgical repair of an acute hip fracture were recruited.

RTP801 interacts with the tRNA ligase complex and dysregulates its RNA ligase activity in Alzheimer's disease.

RTP801/REDD1 is a stress-responsive protein overexpressed in neurodegenerative diseases such as Alzheimer's disease (AD) that contributes to cognitive deficits and neuroinflammation. Here, we found that RTP801 interacts with HSPC117, DDX1 and CGI-99, three members of the tRNA ligase complex (tRNA-LC), which ligates the excised exons of intron-containing tRNAs and the mRNA exons of the transcription factor XBP1 during the unfolded protein response (UPR). We also found that RTP801 modulates the mRNA ligase activity of the complex in vitro since RTP801 knockdown promoted XBP1 splicing and the expression of its transcriptional target, SEC24D.

PD-1/LAG-3 co-signaling profiling uncovers CBL ubiquitin ligases as key immunotherapy targets.

Many cancer patients do not benefit from PD-L1/PD-1 blockade immunotherapies. PD-1 and LAG-3 co-upregulation in T-cells is one of the major mechanisms of resistance by establishing a highly dysfunctional state in T-cells. To identify shared features associated to PD-1/LAG-3 dysfunctionality in human cancers and T-cells, multiomic expression profiles were obtained for all TCGA cancers immune infiltrates.

Proteomic profiling of human plasma extracellular vesicles identifies PF4 and C1R as novel biomarker in sarcopenia.

Background: Sarcopenia, the gradual and generalized loss of muscle mass and function with ageing, is one of the major health problems in older adults, given its high prevalence and substantial socioeconomic implications. Despite the extensive efforts to reach consensus on definition and diagnostic tests and cut-offs for sarcopenia, there is an urgent and unmet need for non-invasive, specific and sensitive biomarkers for the disease. Extracellular vesicles (EVs) are present in different biofluids including plasma, whose cargo reflects cellular physiology.

Drug-Induced Reorganisation of Lipid Metabolism Limits the Therapeutic Efficacy of Ponatinib in Glioma Stem Cells.

The standard of care for glioblastoma (GBM) involves surgery followed by adjuvant radio- and chemotherapy, but often within months, patients relapse, and this has been linked to glioma stem cells (GSCs), self-renewing cells with increased therapy resistance. The identification of the epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR) as key players in gliomagenesis inspired the development of inhibitors targeting these tyrosine kinases (TKIs). However, results from clinical trials testing TKIs have been disappointing, and while the role of GSCs in conventional therapy resistance has been extensively studied, less is known about resistance of GSCs to TKIs.

Application of Graph Models to the Identification of Transcriptomic Oncometabolic Pathways in Human Hepatocellular Carcinoma.

Whole-tissue transcriptomic analyses have been helpful to characterize molecular subtypes of hepatocellular carcinoma (HCC). Metabolic subtypes of human HCC have been defined, yet whether these different metabolic classes are clinically relevant or derive in actionable cancer vulnerabilities is still an unanswered question. Publicly available gene sets or gene signatures have been used to infer functional changes through gene set enrichment methods.

Formation of Microcapsules of Pullulan by Emulsion Template Mechanism: Evaluation as Vitamin C Delivery Systems.

Pullulan is a polysaccharide that has attracted the attention of scientists in recent times as a former of edible films. On the other hand, its use for the preparation of hydrogels needs more study, as well as the formation of pullulan microcapsules as active ingredient release systems for the food industry. Due to the slow gelation kinetics of pullulan with sodium trimetaphosphate (STMP), capsules cannot be formed through the conventional method of dropping into a solution of the gelling agent, as with other polysaccharides, since the pullulan chains migrate to the medium before the capsules can form by gelation.

Latreille (Diptera, Ceratopogonidae) of Colombia: records from the collection of insects of medical importance from National Institute of Health.

Background: The collection of insects of medical importance from the Instituto Nacional de Salud, INS (Bogotá, Colombia: https://www.ins.gov.

Motor skill learning modulates striatal extracellular vesicles' content in a mouse model of Huntington's disease.

Huntington's disease (HD) is a neurological disorder caused by a CAG expansion in the Huntingtin gene (HTT). HD pathology mostly affects striatal medium-sized spiny neurons and results in an altered cortico-striatal function. Recent studies report that motor skill learning, and cortico-striatal stimulation attenuate the neuropathology in HD, resulting in an amelioration of some motor and cognitive functions.

Neuropilin-1 sex-dependently modulates inflammatory, angiogenic and osteogenic phenotypes in the calcifying valve interstitial cell.

The pathological mechanisms underlying the sex-dependent presentation of calcific aortic stenosis (AS) remain poorly understood. We aim to analyse sex-specific responses of valve interstitial cells (VICs) to calcific environments and to identify new pathological and potentially druggable targets. First, VICs from stenotic patients were modelled using pro-calcifying media (HP).

Involvement of Glucosamine 6 Phosphate Isomerase 2 (GNPDA2) Overproduction in β-Amyloid- and Tau P301L-Driven Pathomechanisms.

Alzheimer's disease (AD) is a neurodegenerative olfactory disorder affecting millions of people worldwide. Alterations in the hexosamine- or glucose-related pathways have been described through AD progression. Specifically, an alteration in glucosamine 6 phosphate isomerase 2 (GNPDA2) protein levels has been observed in olfactory areas of AD subjects.

New insights into the regulation of bile acids synthesis during the early stages of liver regeneration: A human and experimental study.

Background And Aims: Liver regeneration is essential for the preservation of homeostasis and survival. Bile acids (BAs)-mediated signaling is necessary for liver regeneration, but BAs levels need to be carefully controlled to avoid hepatotoxicity. We studied the early response of the BAs-fibroblast growth factor 19 (FGF19) axis in healthy individuals undergoing hepatectomy for living donor liver transplant.

Effects of Exercise Intervention for the Management of Delirium in Hospitalized Older Adults: A Randomized Clinical Trial.

Objective: Delirium is a serious neuropsychiatric syndrome frequently occurring in hospitalized older adults, for which pharmacological treatments have shown limited effectiveness. Multicomponent physical exercise programs have demonstrated functional benefits; however, the impact of exercise on the course of delirium remains unexplored. The aim of this study was to investigate the effect of an individualized, multicomponent exercise intervention on the evolution of delirium and patient outcomes.