The short-chain fatty acid receptors Gpr41/43 regulate bone mass by promoting adipogenic differentiation of mesenchymal stem cells.

Bone is a dynamic tissue that is constantly remodeled throughout adult life. Recently, it has been shown that bone turnover decreases shortly after food consumption. This process has been linked to the fermentation of non-digestible food ingredients such as inulin by gut microbes, which results in the production of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate.

The triglyceride-synthesizing enzyme diacylglycerol acyltransferase 2 modulates the formation of the hepatitis C virus replication organelle.

The replication organelle of hepatitis C virus (HCV), called membranous web, is derived from the endoplasmic reticulum (ER) and mainly comprises double membrane vesicles (DMVs) that concentrate the viral replication complexes. It also tightly associates with lipid droplets (LDs), which are essential for virion morphogenesis. In particular acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), a rate-limiting enzyme in triglyceride synthesis, promotes early steps of virus assembly.

An efficient AAV vector system of Rec2 serotype for intravenous injection to study metabolism in brown adipocytes in vivo.

Objective: Recombinant adeno-associated virus (rAAV) vectors are powerful tools for the sustained expression of proteins in vivo and have been successfully used for mechanistic studies in mice. A major challenge associated with this method is to obtain tissue specificity and high expression levels without need of local virus administration.

Methods: To achieve this goal for brown adipose tissue (BAT), we developed a rAAV vector for intravenous bolus injection, which includes an expression cassette comprising an uncoupling protein-1 enhancer-promoter for transcription in brown adipocytes and miR122 target sequences for suppression of expression in the liver, combined with packaging in serotype Rec2 capsid protein.

Sex differences in lipidomic and bile acid plasma profiles in patients with and without coronary artery disease.

Background: Lipids, including phospholipids and bile acids, exert various signaling effects and are thought to contribute to the development of coronary artery disease (CAD). Here, we aimed to compare lipidomic and bile acid profiles in the blood of patients with and without CAD stratified by sex.

Methods: From 2015 to 2022, 3,012 patients who underwent coronary angiography were recruited in the INTERCATH cohort.

Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use.

Dietary polyunsaturated fatty acids (PUFA) are increasingly recognized for their health benefits, whereas a high production of endogenous fatty acids - a process called de novo lipogenesis (DNL) - is closely linked to metabolic diseases. Determinants of PUFA incorporation into complex lipids are insufficiently understood and may influence the onset and progression of metabolic diseases. Here we show that fatty acid synthase (FASN), the key enzyme of DNL, critically determines the use of dietary PUFA in mice and humans.

Lipidome Analysis of Oropharyngeal Tumor Tissues Using Nanosecond Infrared Laser (NIRL) Tissue Sampling and Subsequent Mass Spectrometry.

Ultrashort pulse infrared lasers can simultaneously sample and homogenize biological tissue using desorption by impulsive vibrational excitation (DIVE). With growing attention on alterations in lipid metabolism in malignant disease, mass spectrometry (MS)-based lipidomic analysis has become an emerging topic in cancer research. In this pilot study, we investigated the feasibility of tissue sampling with a nanosecond infrared laser (NIRL) for the subsequent lipidomic analysis of oropharyngeal tissues, and its potential to discriminate oropharyngeal squamous cell carcinoma (OPSCC) from non-tumorous oropharyngeal tissue.

Loss of hepatic SMLR1 causes hepatosteatosis and protects against atherosclerosis due to decreased hepatic VLDL secretion.

Background And Aims: The assembly and secretion of VLDL from the liver, a pathway that affects hepatic and plasma lipids, remains incompletely understood. We set out to identify players in the VLDL biogenesis pathway by identifying genes that are co-expressed with the MTTP gene that encodes for microsomal triglyceride transfer protein, key to the lipidation of apolipoprotein B, the core protein of VLDL. Using human and murine transcriptomic data sets, we identified small leucine-rich protein 1 ( SMLR1 ), encoding for small leucine-rich protein 1, a protein of unknown function that is exclusively expressed in liver and small intestine.

Diagnostic potential of extracellular vesicles in meningioma patients.

Background: Extracellular vesicles (EVs) play an important role in cell-cell communication, and tumor-derived EVs circulating in patient blood can serve as biomarkers. Here, we investigated the potential role of plasma EVs in meningioma patients for tumor detection and determined whether EVs secreted by meningioma cells reflect epigenetic, genomic, and proteomic alterations of original tumors.

Methods: EV concentrations were quantified in patient plasma (n = 46).

Role of Endothelial Cell Lipoprotein Lipase for Brown Adipose Tissue Lipid and Glucose Handling.

Cold-induced activation of brown adipose tissue (BAT) has an important impact on systemic lipoprotein metabolism by accelerating the processing of circulating triglyceride-rich lipoproteins (TRL). Lipoprotein lipase (LPL) expressed by adipocytes is translocated via endothelial to the capillary lumen, where LPL acts as the central enzyme for the vascular lipoprotein processing. Based on preliminary data showing that LPL is not only expressed in adipocytes but also in endothelial cells of cold-activated BAT, we aimed to dissect the relevance of endothelial versus adipocyte LPL for lipid and energy metabolism in the context of adaptive thermogenesis.

A Gas Chromatography Mass Spectrometry-Based Method for the Quantification of Short Chain Fatty Acids.

Short Chain Fatty Acids (SCFAs) are produced by the gut microbiota and are present in varying concentrations in the intestinal lumen, in feces but also in the circulatory system. By interacting with different cell types in the body, they have a great impact on host metabolism and their exact quantification is indispensable. Here, we present a derivatization-free method for the gas chromatography mass spectrometry (GC-MS) based quantification of SCFAs in plasma, feces, cecum, liver and adipose tissue.

Susceptibility to diet-induced obesity at thermoneutral conditions is independent of UCP1.

Activation of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) upon cold stimulation leads to substantial increase in energy expenditure to defend body temperature. Increases in energy expenditure after a high-caloric food intake, termed diet-induced thermogenesis, are also attributed to BAT. These properties render BAT a potential target to combat diet-induced obesity.

Design, synthesis and biological evaluation of glycolamide, glycinamide, and β-amino carbonyl 1,2,4-triazole derivatives as DPP-4 inhibitors.

Through modification of the skeleton of Sitagliptin and Vildagliptin, we successfully synthesized and built-up four series of 1,2,4-triazole derivatives, containing N,O-disubstituted glycolamide, N,N'-disubstituted glycinamide, β-amino ester, and β-amino amide as linkers, for the development of new dipeptidyl peptidase 4 (DPP-4) inhibitors. The synthetic strategy for glycolamides or glycinamides involved convenient two-steps reaction: functionalized transformation of 2-chloro-N-(2,4,5-triflurophenyl)acetamide 9 (hydroxylation or amination) and esterification or amidation of 1,2,4-triazole-3-carboxylic acid. On the other hand, the one-pot synthesis procedure, including substitution and deprotection, was developed for the preparation of β-amino carbonyl 1,2,4-triazoles from (1H-1,2,4-triazol-3-yl)methanol 12 or (1H-1,2,4-triazol-3-yl)methanamine 13 and Boc-(R)-3-amino-4-(2,4,5-trifluoro-phenyl)-butyric acid 14.

Genome-wide methylation profiling of glioblastoma cell-derived extracellular vesicle DNA allows tumor classification.

Background: Genome-wide DNA methylation profiling has recently been developed into a tool that allows tumor classification in central nervous system tumors. Extracellular vesicles (EVs) are released by tumor cells and contain high molecular weight DNA, rendering EVs a potential biomarker source to identify tumor subgroups, stratify patients and monitor therapy by liquid biopsy. We investigated whether the DNA in glioblastoma cell-derived EVs reflects genome-wide tumor methylation and mutational profiles and allows noninvasive tumor subtype classification.

New methyl 5-(halomethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates as selective COX-2 inhibitors and anti-inflammatory agents: Design, synthesis, biological evaluation, and docking study.

A new method was developed for synthesis of 1,2,4-triazole-3-carboxylates 5a-p and 6 from nitrilimines 3a-p through amination and heterocyclization two-steps reactions. All of 1,2,4-triazole-3-carboxylates 5 and 6 were characterized by spectroscopy technique. Based on the SAR study of anti-inflammation activity, most of these compounds showed potential anti-inflammatory activity on NO inhibition in LPS-induced RAW 264.

Chlorotrimethylsilane promoted one-flask heterocyclic synthesis of 1,2,4-triazoles from nitrilimines: Modeling studies and bioactivity evaluation of LH-21 and Rimonabant analogues.

An efficient one-flask cascade method for synthesis of the multi-substituted 1,2,4-triazoles via chlorotrimethylsilane as a promoter was developed. Firstly, nitrilimines were transformed to hydrazonamides as intermediate in high yield by treatment with commercially available hexamethyldisilazane. Subsequently, the mixture was added with corresponding acyl chloride and heated in the presence of pyridine to give the corresponding multi-substituted 1,2,4-triazoles via chlorotrimethylsilane promoted heterocyclization reaction.

The State of Maternal and Infant Health and Mortality in Chad.

The level of Chad's government expenditure on health is a predictor of the general health of the population and, consequently, life expectancy. We used data from the World Bank's World Development Indicators and publications from the World Health Organization to assess the state of maternal and infant health and mortality. The primary objective of this research was to investigate whether Chad had reduced the risk of maternal and infant mortality after signing the Abuja Declaration in 2001.

Towards OCT-Navigated Tissue Ablation with a Picosecond Infrared Laser (PIRL) and Mass-Spectrometric Analysis.

Medical lasers are commonly used in interventions to ablate tumor tissue. Recently, the picosecond infrared laser has been introduced, which greatly decreases damaging of surrounding healthy tissue. Further, its ablation plume contains intact biomolecules which can be collected and analyzed by mass spectrometry.

Simultaneous determination of nitrate and nitrite in vegetables by poly(vinylimidazole-co-ethylene dimethacrylate) monolithic capillary liquid chromatography with UV detection.

Simultaneous determination of nitrate (NO) and nitrite (NO) in vegetables was performed on a poly(1-vinylimidazole-co-ethylene dimethacrylate) (VIM-EDMA) monolithic column by capillary liquid chromatography (LC) with UV detection. Good linearity (0.5-100 μg mL i.

Mass Spectrometric Lipid Profiles of Picosecond Infrared Laser-Generated Tissue Aerosols Discriminate Different Brain Tissues.

Background And Objectives: A picosecond infrared laser (PIRL) has recently been demonstrated to cut biological tissue without scar formation based on the minimal destructive action on the surrounding cells. During cutting with PIRL, the irradiated tissue is ablated by a cold vaporization process termed desorption by impulsive vibrational excitation. In the resulting aerosol, all molecules are dissolved in small droplets and even labile biomolecules like proteins remain intact after ablation.

Proteome analysis of human mesenchymal stem cells undergoing chondrogenesis when exposed to the products of various magnesium-based materials degradation.

Treatment of physeal fractures (15%-30% of all paediatric fractures) remains a challenge as in approximately 10% of the cases, significant growth disturbance may occur. Bioresorbable Magnesium-based implants represent a strategy to minimize damage (., load support until bone healing without second surgery).

Separation of inorganic anions by capillary ion chromatography with UV detection using poly(vinylimidazole-co-ethylene dimethacrylate) monolithic column.

Poly(1-vinylimidazole-co-ethylene dimethacrylate) (VIM-EDMA) monolithic stationary phase was applied for separation of inorganic anions by capillary ion chromatography (IC). The retention of inorganic anions on the VIM-EDMA column was investigated using various salt solutions as the eluent. Good separation of inorganic anions was obtained on VIM-EDMA monolithic column using NHCl as the eluent.

Preparation and characterization of vinylimidazole-based polymer monolithic stationary phases for reversed-phase and hydrophilic interaction capillary liquid chromatography.

In this study, we applied 1-vinylimidazole (VIM) as the functional monomer to prepare a series of VIM-based monolithic stationary phases for both reversed-phase and hydrophilic interaction capillary liquid chromatography (LC) using various dimethacrylates (EDMA: ethylene dimethacrylate; HDDMA: 1,6-hexanediol dimethacrylate; DDDMA: 1,10-decanediol dimethacrylate) as cross-linkers. With a simple thermally initiated free-radical cross-linking polymerization process, VIM-based monolithic stationary phases have been successfully prepared. The porosity, permeability, and column efficiency of synthesized VIM-based monolithic stationary phases were characterized.

Quantification of 7-aminoflunitrazepam in human urine by polymeric monolith-based capillary liquid chromatography coupled to tandem mass spectrometry.

Using a simple liquid-liquid extraction (LLE) procedure for sample pretreatment, 7-Aminoflunitrazepam (7-aminoFM2), a major metabolite of flunitrazepam (FM2), was determined in urine samples by polymeric monolith-based capillary liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The linearity was found in the range of 0.1-50ngmL with a method detection limit (signal-to-noise ratio of 3) estimated at 0.

Determination of sulfonamides in animal tissues by modified QuEChERS and liquid chromatography tandem mass spectrometry.

In this study, the salting-out solvent extraction and dispersive solid-phase extraction (dSPE) clean-up steps in QuEChERS (quick, easy, cheap, effective, rugged, and safe) method were optimized to reduce matrix effect and efficiently extract target sulfonamides from a variety of edible animal tissues. The extracted sulfonamides were then analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Good extraction recoveries (74.

Chromatographic selectivity of poly(alkyl methacrylate-co-divinylbenzene) monolithic columns for polar aromatic compounds by pressure-driven capillary liquid chromatography.

In this study, divinylbenzene (DVB) was used as the cross-linker to prepare alkyl methacrylate (AlMA) monoliths for incorporating π-π interactions between the aromatic analytes and AlMA-DVB monolithic stationary phases in capillary LC analysis. Various AlMA/DVB ratios were investigated to prepare a series of 30% AlMA-DVB monolithic stationary phases in fused-silica capillaries (250-μm i.d.