Semaphorin-3A regulates liver sinusoidal endothelial cell porosity and promotes hepatic steatosis.

Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, increases worldwide and associates with type 2 diabetes and other cardiometabolic diseases. Here we demonstrate that Sema3a is elevated in liver sinusoidal endothelial cells of animal models for obesity, type 2 diabetes and MASLD. In primary human liver sinusoidal endothelial cells, saturated fatty acids induce expression of SEMA3A, and loss of a single allele is sufficient to reduce hepatic fat content in diet-induced obese mice.

Knock-out of dipeptidase CN2 in human proximal tubular cells disrupts dipeptide and amino acid homeostasis and para- and transcellular solute transport.

Aim: Although of potential biomedical relevance, dipeptide metabolism has hardly been studied. We found the dipeptidase carnosinase-2 (CN2) to be abundant in human proximal tubules, which regulate water and solute homeostasis. We therefore hypothesized, that CN2 has a key metabolic role, impacting proximal tubular transport function.

Identification of myeloid-derived growth factor as a mechanically-induced, growth-promoting angiocrine signal for human hepatocytes.

Recently, we have shown that after partial hepatectomy (PHx), an increased hepatic blood flow initiates liver growth in mice by vasodilation and mechanically-triggered release of angiocrine signals. Here, we use mass spectrometry to identify a mechanically-induced angiocrine signal in human hepatic endothelial cells, that is, myeloid-derived growth factor (MYDGF). We show that it induces proliferation and promotes survival of primary human hepatocytes derived from different donors in two-dimensional cell culture, via activation of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3).

Knock-Out Reduces Kidney Fibrosis in Type-1 Diabetic Mice on High Fat Diet.

Carnosine and anserine supplementation markedLy reduce diabetic nephropathy in rodents. The mode of nephroprotective action of both dipeptides in diabetes, via local protection or improved systemic glucose homeostasis, is uncertain. Global carnosinase-1 knockout mice (-KO) and wild-type littermates (WT) on a normal diet (ND) and high fat diet (HFD) ( = 10/group), with streptozocin (STZ)-induced type-1 diabetes ( = 21-23/group), were studied for 32 weeks.

Pancreatic islet protection at the expense of secretory function involves serine-linked mitochondrial one-carbon metabolism.

Type 2 diabetes is characterized by insulin hypersecretion followed by reduced glucose-stimulated insulin secretion (GSIS). Here we show that acute stimulation of pancreatic islets with the insulin secretagogue dextrorphan (DXO) or glibenclamide enhances GSIS, whereas chronic treatment with high concentrations of these drugs reduce GSIS but protect islets from cell death. Bulk RNA sequencing of islets shows increased expression of genes for serine-linked mitochondrial one-carbon metabolism (OCM) after chronic, but not acute, stimulation.

Micro-respirometry of whole cells and isolated mitochondria.

Oxygen consumption is a key metric of metabolism in aerobic organisms. Current respirometric methods led to seminal discoveries despite limitations such as high sample demand, exchange with atmospheric O, and cumulative titration protocols leading to limited choice of useable tissue, complex data interpretation, and restricted experimental design. We developed a sensitive and customizable method of measuring O consumption rates by a variety of biological samples in microliter volumes without interference from the aerobic environment.

Chronic Granulomatous Disease First Diagnosed in Adulthood Presenting With Spinal Cord Infection.

Chronic granulomatous disease (CGD) is a rare genetic immunodeficiency, which is characterized by recurrent severe bacterial and fungal infections caused by a defect in phagocytic cells due to loss of superoxide production. The disease usually manifests within the first years of life. Early diagnosis allows therapeutic intervention to improve the limited life expectancy.

Legionnaires' disease in immunocompromised patients: a case report of Legionella longbeachae pneumonia and review of the literature.

In addition to Legionella pneumophila, about 20 Legionella species have been documented as human pathogens. The majority of infections by non-pneumophila Legionella species occur in immunocompromised and splenectomized patients. Here, we report a case of 'classical' lobar pneumonia caused by Legionella longbeachae in a splenectomized patient receiving corticosteroids for chronic immune thrombocytopenia.

An infection with linezolid-resistant S. aureus in a patient with left ventricular assist system.

We report an infection with a linezolid-resistant S. aureus in a patient with a left ventricular assist system. Linezolid should be used with caution when invasive devices or foreign materials are in place or therapeutic courses last longer than 14 d.

Diagnostic value of procalcitonin serum levels in comparison with C-reactive protein in allogeneic stem cell transplantation.

Background And Objectives: Infections represent the major complications following allogeneic stem cell transplantation (SCT). A promising marker for a more specific and early detection of bacterial or fungal infections is procalcitonin (PCT).

Design And Methods: Maximum values (m) and increase (Delta) of PCT and C-reactive protein (CRP) were prospectively analyzed during 214 clinical events in a cohort of 61 patients undergoing allogeneic SCT.