A combination of metformin and galantamine exhibits synergistic benefits in the treatment of sarcopenia.

Age-associated sarcopenia, characterized by a progressive loss in muscle mass and strength, is the largest cause of frailty and disability in the elderly worldwide. Current treatments involve nonpharmacological guidelines that few subjects can abide by, highlighting the need for effective drugs. Preclinical models were employed to test the benefits of RJx-01, a combination drug composed of metformin and galantamine, on sarcopenia.

Resident Esophageal Microbiota Dysbiosis Correlates with Cancer Risk in Barrett's Esophagus Patients and Is Linked to Low Adherence to WCRF/AICR Lifestyle Recommendations.

Esophageal adenocarcinoma (EAC) is the consequence of longstanding gastroesophageal reflux, which leads to inflammation and could cause Barrett's esophagus (BE), the main risk factor for EAC development. The 5 year survival rate of EAC is poor since the diagnosis occurs at the late stage of the disease. To improve patient management, a better comprehension of the mechanism undergoing the evolution through to adenocarcinoma is needed.

A Nutraceutical Formulation Containing Brown Algae Reduces Hepatic Lipid Accumulation by Modulating Lipid Metabolism and Inflammation in Experimental Models of NAFLD and NASH.

Recently, some preclinical and clinical studies have demonstrated the ability of brown seaweeds in reducing the risk factors for metabolic syndrome. Here, we analyzed the beneficial effect of a nutraceutical formulation containing a phytocomplex extracted from seaweeds and chromium picolinate in animal models of liver steatosis of differing severities (rats with non-alcoholic fatty liver disease (NAFLD) and its complication, non-alcoholic steatohepatitis (NASH)). This treatment led to a significant drop in hepatic fat deposition in both models (p < 0.

Temperature-Related Effects of Myocardial Protection Strategies in Swine Hearts after Prolonged Warm Ischemia.

Insufficient supply of cardiac grafts represents a severe obstacle in heart transplantation. Donation after circulatory death (DCD), in addition to conventional donation after brain death, is one promising option to overcome the organ shortage. However, DCD organs undergo an inevitably longer period of unprotected warm ischemia between circulatory arrest and graft procurement.

Insulin/IGF-1 Signaling Is Downregulated in Barrett's Esophagus Patients Undergoing a Moderate Calorie and Protein Restriction Program: A Randomized 2-Year Trial.

Obesity and associated insulin resistance (Ins-R) have been identified as important risk factors for esophageal adenocarcinoma development. Elevated calories and protein consumption are also associated with Ins-R and glucose intolerance. We investigated the effect of a 24-month moderate calorie and protein restriction program on overweight or obese patients affected by Barrett's esophagus (BE), as no similar dietary approach has been attempted to date in this disease context.

Lomitapide does not alter PCSK9 and Lp(a) levels in homozygous familial hypercholesterolemia patients: Analysis on cytokines and lipid profile.

Lomitapide, a drug for the treatment of homozygous familial hypercholesterolemia patients, reduced total and LDL cholesterol but no significant changes were observed on PCSK9 and Lp(a) plasma levels. Some changes of inflammatory mediators were also observed, including hsCRP, which may suggest an anti-inflammatory effect.

Age-severity matched cytokine profiling reveals specific signatures in Covid-19 patients.

A global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcomes, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell exhaustion, and the increased levels of inflammatory mediators have been described in COVID-19 patients, in particular in severe cases.

Circulating microRNA expression profiling revealed miR-92a-3p as a novel biomarker of Barrett's carcinogenesis.

The main intent of secondary prevention strategies for Barrett's esophagus (BE) patients relies in the prompt identification of patients with dysplasia (or intra-epithelial neoplasia; IEN) and early-stage adenocarcinoma (Barrett's adenocarcinoma; BAc). Despite the adequate characterization of the molecular landscape characterizing Barrett's carcinogenesis, no tissue and/or circulating biomarker has been approved for clinical use. A series of 25 serum samples (12 BE, 5 HG-IEN and 8 BAc) were analyzed for comprehensive miRNA profiling and ten miRNAs were found to be significantly dysregulated.

Insulin/IGF1 signalling mediates the effects of β -adrenergic agonist on muscle proteostasis and growth.

Background: Stimulation of β -adrenoceptors can promote muscle hypertrophy and fibre type shift, and it can counteract atrophy and weakness. The underlying mechanisms remain elusive.

Methods: Fed wild type (WT), 2-day fasted WT, muscle-specific insulin (INS) receptor (IR) knockout (M-IR ), and MKR mice were studied with regard to acute effects of the β -agonist formoterol (FOR) on protein metabolism and signalling events.

Hyperinsulinemia Promotes Esophageal Cancer Development in a Surgically-Induced Duodeno-Esophageal Reflux Murine Model.

Hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion, Barrett's Esophagus, a possible consequence of Gastro-Esophageal Reflux Disease. Obesity is known to mediate esophageal carcinogenesis through different mechanisms including insulin-resistance leading to hyperinsulinemia, which may mediate cancer progression via the insulin/insulin-like growth factor axis. We used the hyperinsulinemic non-obese FVB/N (Friend leukemia virus B strain) MKR (muscle (M)-IGF1R-lysine (K)-arginine (R) mouse model to evaluate the exclusive role of hyperinsulinemia in the pathogenesis of EAC related to duodeno-esophageal reflux.

Sex-dependent differences in inflammatory responses during liver regeneration in a murine model of acute liver injury.

A sexual dimorphism in liver inflammation and repair was previously demonstrated. Its cellular dissection in the course of acute liver injury (ALI) was explored. BALB/c mice were treated with carbon tetrachloride (CCl) by intraperitoneal injection and killed after 3, 5, and 8 days.

Early miR-223 Upregulation in Gastroesophageal Carcinogenesis.

Objectives: To test miR-223 upregulation during gastric (intestinal-type) and Barrett esophageal carcinogenesis.

Methods: miR-223 expression was assessed by quantitative reverse transcription polymerase chain reaction in a series of 280 gastroesophageal biopsy samples representative of the whole spectrum of phenotypic changes involved in both carcinogenetic cascades. The results were further validated by in situ hybridization on multiple tissue specimens obtained from six surgically treated gastroesophageal adenocarcinomas.

Insulin promotes HER2 signaling activation during Barrett's Esophagus carcinogenesis.

Background: Insulin-resistance and hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion Barrett's Esophagus (BE). HER2 activation has also a pivotal role in EAC carcinogenesis but no data correlate these two phenomena in this disease context.

Aims: To investigate the role of hyperinsulinemia in BE-dysplasia-adenocarcinoma sequence and the possible relationship between insulin-mediated and HER2 signaling in EAC development.

Detection of fluorescent organic nanoparticles by confocal laser endomicroscopy in a rat model of Barrett's esophageal adenocarcinoma.

For many years, novel strategies for cancer detection and treatment using nanoparticles (NPs) have been developed. Esophageal adenocarcinoma is the sixth leading cause of cancer-related deaths in Western countries, and despite recent advances in early detection and treatment, its prognosis is still very poor. This study investigated the use of fluorescent organic NPs as potential diagnostic tool in an experimental in vivo model of Barrett's esophageal adenocarcinoma.

Adherence to WCRF/AICR lifestyle recommendations for cancer prevention and the risk of Barrett's esophagus onset and evolution to esophageal adenocarcinoma: results from a pilot study in a high-risk population.

Purpose: While adherence to the World Cancer Research Fund (WCRF) guidelines on lifestyle and cancer was recently proven to be associated with an increased risk of esophageal cancer, no investigation has yet been carried out on its role on Barrett's esophagus (BE) development and its progression to esophageal adenocarcinoma (EAC). The primary aim of this study was to evaluate the role of adherence to WCRF lifestyle recommendations in BE onset and progression. The secondary aim was to investigate the association between disease progression and specific aspects of diet and lifestyle.

Umbilical cord mesenchymal stem cells modulate dextran sulfate sodium induced acute colitis in immunodeficient mice.

Introduction: Inflammatory bowel diseases (IBD) are complex multi-factorial diseases with increasing incidence worldwide but their treatment is far from satisfactory. Unconventional strategies have consequently been investigated, proposing the use of cells as an effective alternative approach to IBD. In the present study we examined the protective potential of exogenously administered human umbilical cord derived mesenchymal stem cells (UCMSCs) against Dextran Sulfate Sodium (DSS) induced acute colitis in immunodeficient NOD.

Systemic administration of a novel human umbilical cord mesenchymal stem cells population accelerates the resolution of acute liver injury.

Background: Hepatocytes and stem cells transplantation may be an alternative to liver transplantation in acute or chronic liver disease. We aimed to evaluate the therapeutic potential of mesenchymal stem cells from human umbilical cord (UCMSCs), a readily available source of mesenchymal stem cells, in the CCl4-induced acute liver injury model.

Methods: Mesenchymal stem cells profile was analyzed by flow cytometry.

The Vibrio cholerae cytolysin promotes chloride secretion from intact human intestinal mucosa.

Background: The pathogenicity of the Vibrio cholerae strains belonging to serogroup O1 and O139 is due to the production of virulence factors such as cholera toxin (CT) and the toxin-coregulated pilus (TCP). The remaining serogroups, which mostly lack CT and TCP, are more frequently isolated from aquatic environmental sources than from clinical samples; nevertheless, these strains have been reported to cause human disease, such as sporadic outbreaks of watery diarrhoea and inflammatory enterocolitis. This evidence suggested the possibility that other virulence factor(s) than cholera toxin might be crucial in the pathogenesis of Vibrio cholerae-induced diarrhoea, but their nature remains unknown.

The Vibrio cholerae cytolysin promotes activation of mast cell (T helper 2) cytokine production.

Many strains of Vibrio cholerae produce a cytolysin (VCC) that forms oligomeric transmembrane pores responsible for vacuolization of several cell types in culture. Here we suggest that VCC could contribute to the T helper 2 (Th2) response seen in the natural infection; acting through TLR2, VCC enhances mast cells secretion of IL-4, IL-6 and TNF-alpha by 330-, 290- and 550-fold respectively. Moreover, VCC-induced cytokine production is dependent on increased cytosolic Ca(2+) and on the presence of the Src family kinases Lyn and Fyn, known to be required for FcepsilonRI-dependent activation of mast cells.

Dopamine inhibits responses of astroglia-enriched cultures to lipopolysaccharide via a beta-adrenoreceptor-mediated mechanism.

We here investigated the effect of the catecholaminergic neurotransmitter dopamine (DA), on the release of two major inflammatory effectors, TNF-alpha and nitric oxide, in rat astroglia-enriched cultures stimulated with the bacterial endotoxin lipopolysaccharide (LPS). Upon LPS challenge, we observed a dramatic increase in the culture medium of the TNF-alpha protein, an effect thereafter followed by an increase of nitric oxide synthase type 2 (NOS2) mRNA and, at later times, of nitrite accumulation, an index of nitric oxide (NO) production. DA substantially inhibited the release of TNF-alpha and NO evoked by LPS, an effect not mimicked by selective agonists nor prevented by selective antagonists of the DA receptors.