-
Expert Review of Clinical Immunology 2023
Topics: Humans; Anaphylaxis; Food Hypersensitivity; Allergens; Epinephrine
PubMed: 37753864
DOI: 10.1080/1744666X.2023.2265069 -
Molecular Metabolism Dec 2023Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality worldwide. Current strategies to manage ALD focus largely on advanced stage...
Ceramide synthase 6 (CerS6) is upregulated in alcohol-associated liver disease and exhibits sex-based differences in the regulation of energy homeostasis and lipid droplet accumulation.
OBJECTIVE
Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality worldwide. Current strategies to manage ALD focus largely on advanced stage disease, however, metabolic changes such as glucose intolerance are apparent at the earliest stage of alcoholic steatosis and increase the risk of disease progression. Ceramides impair insulin signaling and accumulate in ALD, and metabolic pathways involving ceramide synthase 6 (CerS6) are perturbed in ALD during hepatic steatosis. In this study, we aimed to investigate the role of CerS6 in ALD development and the relevance of CerS6 to human ALD.
METHODS
C57BL/6 WT and CerS6 KO mice of both sexes were fed either a Lieber-DeCarli control (CON) or 15% ethanol (EtOH) diet for six weeks. In vivo metabolic tests including glucose and insulin tolerance tests (GTT and ITT) and energy expenditure were performed. The mice were euthanized, and serum and liver lipids and liver histology were examined. For in vitro studies, CerS6 was deleted in human hepatocytes, VL17A and cells were incubated with EtOH and/or C-ceramides. RNAseq analysis was performed in livers from mice and human patients with different stages of ALD and diseased controls.
RESULTS
After six weeks on an EtOH diet, CerS6 KO mice had reduced body weight, food intake, and %fat mass compared to WT mice. Energy expenditure increased in both male and female KO mice, however, was only statistically significant in male mice. In response to EtOH, WT mice developed mild hepatic steatosis, while steatosis was ameliorated in KO mice as determined by H&E and ORO staining. KO mice showed significantly decreased long-chain ceramide species, especially C-ceramides, in the serum and liver tissues compared to WT mice. CerS6 deletion decreased serum TG and NEFA only in male not female mice. CerS6 deletion improved glucose tolerance and insulin resistance in EtOH-fed mice of both sexes. RNAseq analysis revealed that 74 genes are significantly upregulated and 66 genes are downregulated by CerS6 deletion in EtOH-fed male mice, with key network pathways including TG biosynthetic process, positive regulation of lipid localization, and fat cell differentiation. Similar to RNAseq results, absence of CerS6 significantly decreased mRNA expression of lipid droplet associated proteins in EtOH-fed mice. In vitro, EtOH stimulation significantly increased PLIN2 protein expression in VL17A cells while CerS6 deletion inhibited EtOH-mediated PLIN2 upregulation. C-ceramide treatment significantly increased PLIN2 protein expression compared to CON. Notably, progression of ALD in humans was associated with increased hepatic CerS6 expression.
CONCLUSIONS
Our findings demonstrate that CerS6 deletion improves glucose homeostasis in alcohol-fed mice and exhibits sex-based differences in the attenuation of EtOH-induced weight gain and hepatic steatosis. Additionally, we unveil that CerS6 plays a major role as a regulator of lipid droplet biogenesis in alcohol-induced intra-hepatic lipid droplet formation, identifying it as a putative target for early ALD management.
Topics: Animals; Female; Humans; Male; Mice; Ceramides; Ethanol; Fatty Liver; Glucose; Homeostasis; Insulins; Lipid Droplets; Liver Diseases, Alcoholic; Mice, Inbred C57BL; Perilipin-2
PubMed: 37714377
DOI: 10.1016/j.molmet.2023.101804 -
Allergologie Select 2023Not available.
Guideline for allergological diagnosis of drug hypersensitivity reactions: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Dermatological Society (DDG), the Association of German Allergologists (ÄDA), the German Society for...
Not available.
PubMed: 37705676
DOI: 10.5414/ALX02422E -
Current Research in Food Science 2023Gluten, a group of ethanol-soluble proteins present in the endosperm of cereals, is extensively used in the food industry due to its ability to improve dough properties....
Gluten, a group of ethanol-soluble proteins present in the endosperm of cereals, is extensively used in the food industry due to its ability to improve dough properties. However, gluten is also associated with a range of gluten-related diseases (GRDs), such as wheat allergies, celiac disease, and gluten intolerance. The recommended treatment for GRDs patients is a gluten-free diet. To monitor adherence to this diet, it is necessary to develop gluten-detection systems in food products. Among the available methods, immunodetection systems are the most popular due to their simplicity, reproducibility, and accuracy. The aim of this study was to generate novel high-affinity antibodies against gluten to be used as the primary reactant in an enzyme-linked immunosorbent assay (ELISA) test. These antibodies were developed by constructing an immune library from mRNA obtained from two celiac patients with a high humoral response to gluten-related proteins. The resulting library (composed by 1.1x10) was subjected to selection against gliadin using phage display technology. Following several rounds of selection, the Fab-C was selected, and demonstrated good functionality in ELISA tests, presenting a limit of detection of 15 mg/kg for detection of gluten in spiked mixtures and food products. The methodology can discriminate gluten-free products according to the current legislation.
PubMed: 37680694
DOI: 10.1016/j.crfs.2023.100578 -
Molecular Genetics and Metabolism Nov 2023We report a patient with an extremely rare, combined diagnosis of PMM2-CDG and hereditary fructose intolerance (HFI). By comparing with other patients,...
We report a patient with an extremely rare, combined diagnosis of PMM2-CDG and hereditary fructose intolerance (HFI). By comparing with other patients, under-galactosylation was identified as a feature of HFI. Fructose/sorbitol/sucrose restriction was initiated right afterwards. The patient is at the mild end of the PMM2-CDG spectrum, raising the question of sorbitol's role in the pathogenesis of PMM2-CDG and whether fructose/sorbitol/sucrose restriction could benefit other PMM2-CDG patients. Additionally, epalrestat, an emerging potential PMM2-CDG therapy, may benefit HFI patients.
Topics: Humans; Fructose Intolerance; Congenital Disorders of Glycosylation; Phosphotransferases (Phosphomutases); Fructose; Sorbitol; Sucrose
PubMed: 37597336
DOI: 10.1016/j.ymgme.2023.107682 -
Journal of Clinical Medicine Jul 2023Metabolic syndrome (MetS) can be resolved through active control. We aimed to examine the effect of changes in MetS status on colorectal cancer (CRC) risk. A total of...
Metabolic syndrome (MetS) can be resolved through active control. We aimed to examine the effect of changes in MetS status on colorectal cancer (CRC) risk. A total of 5,704,611 Korean national insurance beneficiaries that received two consecutive biennial mandatory health exams (2009-2011) were followed-up until 2017. MetS was determined as the presence of at least three of five components. Participants were categorized into four groups according to the change in MetS status; MetS-never, -resolved, -developed, or -persistent. A Cox proportional hazards model adjusted for age, sex, smoking, alcohol drinking, and physical exercise was used. Participants who recovered from MetS had a higher risk of CRC than those free of MetS but had a lower risk than those with persistent MetS (HR: 0.91, 95% CI: 0.86-0.95 vs. HR: 0.75, 95% CI: 0.73-0.78; reference: persistence group). Among the five MetS components, resolving high blood pressure, abdominal obesity, and blood sugar had a preventive effect on CRC prevention, while normalization of lipid profile did not reduce CRC risk independently. Resolving MetS could reduce CRC risk compared to having persistent MetS, indicating the necessity of considering control of MetS as a CRC prevention policy.
PubMed: 37568291
DOI: 10.3390/jcm12154889 -
Molecular Microbiology Sep 2023OLE RNA is a ~600-nucleotide noncoding RNA present in many Gram-positive bacteria that thrive mostly in extreme environments, including elevated temperature, salt, and... (Review)
Review
OLE RNA is a ~600-nucleotide noncoding RNA present in many Gram-positive bacteria that thrive mostly in extreme environments, including elevated temperature, salt, and pH conditions. The precise biochemical functions of this highly conserved RNA remain unknown, but it forms a ribonucleoprotein (RNP) complex that localizes to cell membranes. Genetic disruption of the RNA or its essential protein partners causes reduced cell growth under various stress conditions. These phenotypes include sensitivity to short-chain alcohols, cold intolerance, reduced growth on sub-optimal carbon sources, and intolerance of even modest concentrations of Mg . Thus, many bacterial species appear to employ OLE RNA as a component of an intricate RNP apparatus to monitor fundamental cellular processes and make physiological and metabolic adaptations. Herein we hypothesize that the OLE RNP complex is functionally equivalent to the eukaryotic TOR complexes, which integrate signals from various diverse pathways to coordinate processes central to cell growth, replication, and survival.
Topics: RNA; Extremophiles; Bacteria; RNA, Untranslated; Ribonucleoproteins
PubMed: 37469248
DOI: 10.1111/mmi.15129 -
Biosensors & Bioelectronics Oct 2023Desalting of biosamples is crucial for analytical techniques intolerant to abundant salts. However, there is no simple tool to monitor the desalting of low-volume...
Desalting of biosamples is crucial for analytical techniques intolerant to abundant salts. However, there is no simple tool to monitor the desalting of low-volume biosamples so far. Here we developed a handheld capacitively coupled contactless conductivity detector (hCD) as a miniaturized device to measure the conductivity of 75 μL biosamples. Polyether-ether-ketone (PEEK) tubing was selected as the sample reservoir for sample loading via a pipette. Another pipetting of air pushed the sample solution out of the tubing to recollect the sample. Owing to the low sample consumption and easy sample recollection, hC4D is advantageous for testing expensive biosamples, such as viruses and cells. In addition, the whole process of sample injection, conductivity measurement, recollection, and calibration of conductivity can be completed within 1 min. To verify the feasibility of hCD, we monitored the desalting progress of gel filtration (GF) of 200 μL blood samples, ultrafiltration (UF) of 300 μL virus samples, and dialysis of 7 mL cell samples. Three rounds of GF and UF completely removed the salts but led to poor sample recovery. In contrast, low concentrations of residual salts remained and better recovery was achieved after two rounds of GF and UF. We further utilized the hCD to monitor the dialysis and tuned the salt concentration in the cell sample, such that we maintained the viability of cells in a low conductivity environment. These results indicated that hCD is a promising tool for optimizing the desalting procedure of low-volume biosamples.
Topics: Electrophoresis, Capillary; Salts; Biosensing Techniques; Ketones; Polyethylene Glycols; Electric Conductivity
PubMed: 37406479
DOI: 10.1016/j.bios.2023.115482 -
Current Psychology (New Brunswick, N.J.) May 2023The current systematic review sought to identify quantitative empirical studies that focused on the transdiagnostic factors of intolerance of uncertainty, emotional...
The current systematic review sought to identify quantitative empirical studies that focused on the transdiagnostic factors of intolerance of uncertainty, emotional dysregulation and rumination, and their relation with depression and post-traumatic stress disorder (PTSD). The overall research aim was to examine the relationship between these transdiagnostic factors and their relation with depression and PTSD symptoms. The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Out of the 768 articles initially identified, 55 met the inclusion criteria for the current review. The results determined that intolerance of uncertainty is indirectly related to depression and PTSD symptoms, mainly through other factors including emotion dysregulation and rumination. Additionally, emotional dysregulation is a significant predictor of both depression and PTSD symptoms. Rumination is a robust factor related to depression and PTSD symptoms, this relationship was significant in cross-sectional and longitudinal studies. This review provides evidence on the transdiagnostic factors of intolerance of uncertainty, emotional dysregulation and rumination in the relationship with depression and PTSD symptoms.
PubMed: 37359653
DOI: 10.1007/s12144-023-04792-x