A Sarcopenia Index Derived from Malnutrition Parameters in Elderly Haemodialysis Patients.

(1) Background: Persons with chronic kidney disease may have sarcopenia characterized by the loss of muscle mass and loss of muscle strength. However, EWGSOP2 criteria to diagnose sarcopenia are technically challenging, especially in elderly persons on hemodialysis. Sarcopenia may be associated with malnutrition.

Reduction in the Risk of Peripheral Neuropathy and Lower Decrease in Kidney Function with Metformin, Linagliptin or Their Fixed-Dose Combination Compared to Placebo in Prediabetes: A Randomized Controlled Trial.

Objective: To compare the effect of glucose-lowering drugs on peripheral nerve and kidney function in prediabetes.

Methods: Multicenter, randomized, placebo-controlled trial in 658 adults with prediabetes treated for 1 year with metformin, linagliptin, their combination or placebo. Endpoints are small fiber peripheral neuropathy (SFPN) risk estimated by foot electrochemical skin conductance (FESC < 70 μSiemens) and estimated glomerular filtration rate (eGFR).

Fibrosis of Peritoneal Membrane, Molecular Indicators of Aging and Frailty Unveil Vulnerable Patients in Long-Term Peritoneal Dialysis.

Peritoneal membrane status, clinical data and aging-related molecules were investigated as predictors of long-term peritoneal dialysis (PD) outcomes. A 5-year prospective study was conducted with the following endpoints: (a) PD failure and time until PD failure, (b) major cardiovascular event (MACE) and time until MACE. A total of 58 incident patients with peritoneal biopsy at study baseline were included.

Overview of Cellular and Soluble Mediators in Systemic Inflammation Associated with Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent chronic liver disease in Western countries, affecting approximately 25% of the adult population. This condition encompasses a spectrum of liver diseases characterized by abnormal accumulation of fat in liver tissue (non-alcoholic fatty liver, NAFL) that can progress to non-alcoholic steatohepatitis (NASH), characterized by the presence of liver inflammation and damage. The latter form often coexists with liver fibrosis which, in turn, may progress to a state of cirrhosis and, potentially, hepatocarcinoma, both irreversible processes that often lead to the patient's death and/or the need for liver transplantation.

Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity.

Background And Purpose: Selective peroxisome proliferator-activated receptors (PPARs) are widely used to treat metabolic complications; however, the limited effect of PPARα agonists on glucose metabolism and the adverse effects associated with selective PPARγ activators have stimulated the development of novel pan-PPAR agonists to treat metabolic disorders. Here, we synthesized a new prenylated benzopyran (BP-2) and evaluated its PPAR-activating properties, anti-inflammatory effects and impact on metabolic derangements.

Experimental Approach: BP-2 was used in transactivation assays to evaluate its agonism to PPARα, PPARβ/δ and PPARγ.

The Synthetic Flavonoid Hidrosmin Improves Endothelial Dysfunction and Atherosclerotic Lesions in Diabetic Mice.

In diabetes, chronic hyperglycemia, dyslipidemia, inflammation and oxidative stress contribute to the progression of macro/microvascular complications. Recently, benefits of the use of flavonoids in these conditions have been established. This study investigates, in two different mouse models of diabetes, the vasculoprotective effects of the synthetic flavonoid hidrosmin on endothelial dysfunction and atherogenesis.

Alpha-klotho and peritoneal membrane status: A hypothesis generating study.

Background: Long-term success of peritoneal dialysis relies on the integrity of the peritoneal membrane. This proof-of-concept study addressed the hypothesis that fibrosis is already present in the membrane at pre-dialysis and that the membrane status is related to the individual's uraemic fingerprint.

Methods: A clinical-mechanistic, transversal, single-centre study was conducted.

Adipokines in Non-Alcoholic Fatty Liver Disease: Are We on the Road toward New Biomarkers and Therapeutic Targets?

Non-alcoholic fatty liver disease (NAFLD) has become the major cause of chronic hepatic illness and the leading indication for liver transplantation in the future decades. NAFLD is also commonly associated with other high-incident non-communicable diseases, such as cardiovascular complications, type 2 diabetes, and chronic kidney disease. Aggravating the socio-economic impact of this complex pathology, routinely feasible diagnostic methodologies and effective drugs for NAFLD management are unavailable.

Role of Toll-like receptor 4 in intravascular hemolysis-mediated injury.

Massive intravascular hemolysis is a common characteristic of several pathologies. It is associated with the release of large quantities of heme into the circulation, promoting injury in vulnerable organs, mainly kidney, liver, and spleen. Heme activates Toll-like receptor 4 (TLR4), a key regulator of the inflammatory response; however, the role of TLR4 in hemolysis and whether inhibition of this receptor may protect from heme-mediated injury are unknown.

NT-proBNP Levels Influence the Prognostic Value of Mineral Metabolism Biomarkers in Coronary Artery Disease.

Background. Mineral metabolism (MM) system and N-terminal pro-brain natriuretic peptide (NT-ProBNP) have been shown to add prognostic value in patients with stable coronary artery disease (SCAD). However, the influence of NT-ProBNP on the prognostic role of MM in patients with SCAD has not been shown yet.

High Intensity Interval Training reduces hypoglycemic events compared with continuous aerobic training in individuals with type 1 diabetes: HIIT and hypoglycemia in type 1 diabetes.

Aims: to investigate if a High Intensity Interval Training (HIIT) protocol improves glycemic control and fitness capacity, compared to traditional moderate Intensity Continuous Training (MICT) exercise.

Methods: 30 sedentary individuals with type 1 diabetes (T1D) and 26 healthy controls were assigned to a 3-week HIIT or MICT protocol. Blood glucose levels by continuous glucose monitoring system and fitness status were compared before and after the study period.

Application of Machine Learning Solutions to Optimize Parameter Prediction to Enhance Automatic NMR Metabolite Profiling.

The quality of automatic metabolite profiling in NMR datasets from complex matrices can be affected by the numerous sources of variability. These sources, as well as the presence of multiple low-intensity signals, cause uncertainty in the metabolite signal parameters. Lineshape fitting approaches often produce suboptimal resolutions to adapt them in a complex spectrum lineshape.

Meta-Inflammation and De Novo Lipogenesis Markers Are Involved in Metabolic Associated Fatty Liver Disease Progression in BTBR ob/ob Mice.

Metabolic associated fatty liver disease (MAFLD) is a hepatic manifestation of metabolic syndrome and usually associated with obesity and diabetes. Our aim is to characterize the pathophysiological mechanism involved in MAFLD development in Black Tan and brachyuric (BTBR) insulin-resistant mice in combination with leptin deficiency (ob/ob). We studied liver morphology and biochemistry on our diabetic and obese mice model (BTBR ob/ob) as well as a diabetic non-obese control (BTBR + streptozotocin) and non-diabetic control mice (BTBR wild type) from 4-22 weeks.

Kidney microRNA Expression Pattern in Type 2 Diabetic Nephropathy in BTBR Ob/Ob Mice.

Diabetic nephropathy (DN) is the main leading cause of chronic kidney disease worldwide. Although remarkable therapeutic advances have been made during the last few years, there still exists a high residual risk of disease progression to end-stage renal failure. To further understand the pathogenesis of tissue injury in this disease, by means of the Next-Generation Sequencing, we have studied the microRNA (miRNA) differential expression pattern in kidneys of Black and Tan Brachyury (BTBR) ob/ob (leptin deficiency mutation) mouse.

Muscular carnosine is a marker for cardiorespiratory fitness and cardiometabolic risk factors in men with type 1 diabetes.

Purpose: Muscle is an essential organ for glucose metabolism and can be influenced by metabolic disorders and physical activity. Elevated muscle carnosine levels have been associated with insulin resistance and cardiometabolic risk factors. Little is known about muscle carnosine in type 1 diabetes (T1D) and how it is influenced by physical activity.

Revealing 2-dimethylhydrazino-2-alkyl alkynyl sphingosine derivatives as sphingosine kinase 2 inhibitors: Some hints on the structural basis for selective inhibition.

Sphingosine kinase (SphK), which catalyzes the transfer of phosphate from ATP to sphingosine (Sph) generating sphingosine-1-phosphate (S1P) has emerged as therapeutic target since the discovery of connections of S1P with cancer progress. So far, most effort has focused on the development of inhibitors of SphK1, and selective inhibitors of SphK2 have been much less explored. Here, we describe the syntheses of new sphingosine derivatives bearing a tetrasubstituted carbon atom at C-2, dimethylhydrazino or azo moieties in the polar head, and alkane, alkene or alkyne moieties as linkers between the polar ahead and the fatty tail.

CCN2 (Cellular Communication Network Factor 2) Deletion Alters Vascular Integrity and Function Predisposing to Aneurysm Formation.

Background: CCN2 (cellular communication network factor 2) is a matricellular protein involved in cell communication and microenvironmental signaling responses. CCN2 is known to be overexpressed in several cardiovascular diseases, but its role is not completely understood.

Methods: Here, CCN2 involvement in aortic wall homeostasis and response to vascular injury was investigated in inducible <i>Ccn2</i>-deficient mice, with induction of vascular damage by infusion of Ang II (angiotensin II; 15 days), which is known to upregulate CCN2 expression in the aorta.

SALDI-MS and SERS Multimodal Imaging: One Nanostructured Substrate to Rule Them Both.

Imaging techniques based on mass spectrometry or spectroscopy methods inform about the chemical composition of biological tissues or organisms, but they are sometimes limited by their specificity, sensitivity, or spatial resolution. Multimodal imaging addresses these limitations by combining several imaging modalities; however, measuring the same sample with the same preparation using multiple imaging techniques is still uncommon due to the incompatibility between substrates, sample preparation protocols, and data formats. We present a multimodal imaging approach that employs a gold-coated nanostructured silicon substrate to couple surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) and surface-enhanced Raman spectroscopy (SERS).

Multi-Organ Crosstalk with Endocrine Pancreas: A Focus on How Gut Microbiota Shapes Pancreatic Beta-Cells.

Type 2 diabetes (T2D) results from impaired beta-cell function and insufficient beta-cell mass compensation in the setting of insulin resistance. Current therapeutic strategies focus their efforts on promoting the maintenance of functional beta-cell mass to ensure appropriate glycemic control. Thus, understanding how beta-cells communicate with metabolic and non-metabolic tissues provides a novel area for investigation and implicates the importance of inter-organ communication in the pathology of metabolic diseases such as T2D.

Unveiling the Role of the Fatty Acid Binding Protein 4 in the Metabolic-Associated Fatty Liver Disease.

Metabolic-associated fatty liver disease (MAFLD), the main cause of chronic liver disease worldwide, is a progressive disease ranging from fatty liver to steatohepatitis (metabolic-associated steatohepatitis; MASH). Nevertheless, it remains underdiagnosed due to the lack of effective non-invasive methods for its diagnosis and staging. Although MAFLD has been found in lean individuals, it is closely associated with obesity-related conditions.

Paternal Exercise Improves the Metabolic Health of Offspring via Epigenetic Modulation of the Germline.

Background/aims: Epigenetic regulation is considered the main molecular mechanism underlying the developmental origin of health and disease's (DOHAD) hypothesis. Previous studies that have investigated the role of paternal exercise on the metabolic health of the offspring did not control for the amount and intensity of the training or possible effects of adaptation to exercise and produced conflicting results regarding the benefits of parental exercise to the next generation. We employed a precisely regulated exercise regimen to study the transgenerational inheritance of improved metabolic health.

Relationship Between Fatty Acid Binding Protein 4 and Liver Fat in Individuals at Increased Cardiometabolic Risk.

Liver steatosis is considered the onset of the non-alcoholic fatty liver disease (NAFLD), a major public health challenge. Nevertheless, NAFLD detection and diagnosis remain a difficult task. Fatty acid binding protein 4 (FABP4) has been proposed as potential biomarker for the ectopic fat accumulation in non-adipose tissues, although its role reflecting liver steatosis in metabolic patients is not fully explored.