Intraintestinal fermentation of fructo- and galacto-oligosaccharides and the fate of short-chain fatty acids in humans.

Consumption of fructo- (FOS) and galacto-oligosaccharides (GOS) has health benefits which have been linked in part to short-chain fatty acids (SCFA) production by the gut microbiota. However, detailed knowledge of this process in the human intestine is lacking. We aimed to determine the acute fermentation kinetics of a FOS:GOS mixture in healthy males using a naso-intestinal catheter for sampling directly in the ileum or colon.

Heptanoate Improves Compensatory Mechanism of Glucose Homeostasis in Mitochondrial Long-Chain Fatty Acid Oxidation Defect.

Defects in mitochondrial fatty acid β-oxidation (FAO) impair metabolic flexibility, which is an essential process for energy homeostasis. Very-long-chain acyl-CoA dehydrogenase (VLCADD; OMIM 609575) deficiency is the most common long-chain mitochondrial FAO disorder presenting with hypoglycemia as a common clinical manifestation. To prevent hypoglycemia, triheptanoin-a triglyceride composed of three heptanoates (C7) esterified with a glycerol backbone-can be used as a dietary treatment, since it is metabolized into precursors for gluconeogenesis.

Pyruvate Dehydrogenase Kinase Inhibition by Dichloroacetate in Melanoma Cells Unveils Metabolic Vulnerabilities.

Melanoma is characterized by high glucose uptake, partially mediated through elevated pyruvate dehydrogenase kinase (PDK), making PDK a potential treatment target in melanoma. We aimed to reduce glucose uptake in melanoma cell lines through PDK inhibitors dichloroacetate (DCA) and AZD7545 and through PDK knockdown, to inhibit cell growth and potentially unveil metabolic co-vulnerabilities resulting from PDK inhibition. MeWo cells were most sensitive to DCA, while SK-MEL-2 was the least sensitive, with IC values ranging from 13.

Simultaneous Quantification of the Concentration and Carbon Isotopologue Distribution of Polar Metabolites in a Single Analysis by Gas Chromatography and Mass Spectrometry.

C-isotope tracing is a frequently employed approach to study metabolic pathway activity. When combined with the subsequent quantification of absolute metabolite concentrations, this enables detailed characterization of the metabolome in biological specimens and facilitates computational time-resolved flux quantification. Classically, a C-isotopically labeled sample is required to quantify C-isotope enrichments and a second unlabeled sample for the quantification of metabolite concentrations.

Abdominal Wall Thickness is a Predictor for Surgical Site Infections in Patients Undergoing Colorectal Operations.

Background: Surgical site infections (SSIs) are an established complication following colorectal operations, with rates up to 30% reported in the literature. Obesity is a known risk factor for SSI; however, body mass index (BMI), body fat percentage, waist-hip ratio, or abdominal circumference are imperfect measures. The purpose of our study was to determine whether abdominal wall thickness (AWT) is predictive of SSI.

Breast Implant-associated Anaplastic Large Cell Lymphoma: An Evidence-based Systematic Review.

Objective: This evidence-based systematic review synthesizes and critically appraises current clinical recommendations and advances in the diagnosis and treatment of BIA-ALCL. This review also aims to broaden physician awareness across diverse specialties, particularly among general practitioners, breast surgeons, surgical oncologists, and other clinicians who may encounter patients with breast implants in their practice.

Background: BIA-ALCL is an emerging and treatable immune cell cancer definitively linked to textured-surface breast implants.

Inhibition of Fatty Acid Synthase Upregulates Expression of CD36 to Sustain Proliferation of Colorectal Cancer Cells.

Fatty acid synthase, a key enzyme of lipogenesis, is an attractive therapeutic target in cancer. The novel fatty acid synthase inhibitor, TVB-3664, shows anti-cancer activity in multiple cancers including colorectal cancer; however, it is unclear whether uptake of exogeneous fatty acids can compensate for the effect of fatty acid synthase inhibition. This study demonstrates that inhibition of fatty acid synthase selectively upregulates fatty acid translocase (CD36), a fatty acid transporter, in multiple colorectal cancer models including colorectal cancer cells with shRNA mediated knockdown of fatty acid synthase and genetically modified mouse tissues with heterozygous and homozygous deletion of fatty acid synthase.

SK channel-mediated metabolic escape to glycolysis inhibits ferroptosis and supports stress resistance in C. elegans.

Metabolic flexibility is an essential characteristic of eukaryotic cells in order to adapt to physiological and environmental changes. Especially in mammalian cells, the metabolic switch from mitochondrial respiration to aerobic glycolysis provides flexibility to sustain cellular energy in pathophysiological conditions. For example, attenuation of mitochondrial respiration and/or metabolic shifts to glycolysis result in a metabolic rewiring that provide beneficial effects in neurodegenerative processes.

Cancer stem cell marker expression alone and in combination with microvascular invasion predicts poor prognosis in patients undergoing transplantation for hepatocellular carcinoma.

Background: The cancer stem cell hypothesis provides an explanation for hepatocellular carcinoma (HCC) heterogeneity. We investigated the expression of CD44 and CD133 alone and in combination with microvascular invasion (MVI) as predictors of prognosis in patients undergoing liver transplantation for HCC.

Methods: Explanted livers from 95 patients transplanted for HCC were analyzed.

Noggin attenuates cerulein-induced acute pancreatitis and impaired autophagy.

Objectives: To investigate the role of bone morphogenetic protein (BMP) signaling in acute pancreatitis (AP) by administration of noggin, an endogenous BMP antagonist, in a cerulein-induced AP model.

Methods: Acute pancreatitis was induced by 9 hourly intraperitoneal injections of cerulein (50 μg/kg). Control mice received phosphate-buffered saline injections.