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Biomedicine & Pharmacotherapy =... Jun 2024Liver disease affects millions of people in the world, and China has the highest prevalence of liver disease in the world. Small ubiquitin-related modifier (SUMO)... (Review)
Review
Liver disease affects millions of people in the world, and China has the highest prevalence of liver disease in the world. Small ubiquitin-related modifier (SUMO) modification is a highly conserved post-translational modification of proteins. They are widely expressed in a variety of tissues, including the heart, liver, kidney and lung. SUMOylation of protein plays a key role in the occurrence and development of liver disease. Therefore, this study reviewed the effects of SUMO protein on non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis (HF), hepatocellular carcinoma (HCC), and other liver diseases to provide novel strategies for targeted treatment of liver disease.
PubMed: 38878635
DOI: 10.1016/j.biopha.2024.116898 -
Scientific Reports Jun 2024Exposure to alcohol during adolescence impacts cortical and limbic brain regions undergoing maturation. In rodent models, long-term effects on behavior and...
Exposure to alcohol during adolescence impacts cortical and limbic brain regions undergoing maturation. In rodent models, long-term effects on behavior and neurophysiology have been described after adolescent intermittent ethanol (AIE), especially in males. We hypothesized that AIE in female rats increases conditional approach to a reward-predictive cue and corresponding neuronal activity in the orbitofrontal cortex (OFC) and nucleus accumbens (NAc). We evaluated behavior and neuronal firing after AIE (5 g/kg intragastric) or water (CON) in adult female rats. Both AIE and CON groups expressed a ST phenotype, and AIE marginally increased sign-tracking (ST) and decreased goal-tracking (GT) metrics. NAc neurons exhibited phasic firing patterns to the conditional stimulus (CS), with no differences between groups. In contrast, neuronal firing in the OFC of AIE animals was greater at CS onset and offset than in CON animals. During reward omission, OFC responses to CS offset normalized to CON levels, but enhanced OFC firing to CS onset persisted in AIE. We suggest that the enhanced OFC neural activity observed in AIE rats to the CS could contribute to behavioral inflexibility. Ultimately, AIE persistently impacts the neurocircuitry of reward-motivated behavior in female rats.
Topics: Animals; Female; Prefrontal Cortex; Rats; Ethanol; Reward; Nucleus Accumbens; Neurons; Conditioning, Classical; Behavior, Animal; Cues; Rats, Sprague-Dawley
PubMed: 38877100
DOI: 10.1038/s41598-024-64036-1 -
Scientific Reports Jun 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a predominant liver disease worldwide, lacking approved drugs for clinical intervention...
Association between the composite dietary antioxidant index and metabolic dysfunction-associated steatotic liver disease in adults: a cross-sectional study from NHANES 2017-2020.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a predominant liver disease worldwide, lacking approved drugs for clinical intervention at present. The composite dietary antioxidant index (CDAI) is used to assess the anti-inflammatory properties of diets, with higher CDAI indicating greater exposure to antioxidants. Therefore, our study aimed to explore the relationship between CDAI and MASLD in order to identify potential therapeutic approaches. We collected data from 12,286 participants in the National Health and Nutrition Examination Survey (NHANES) database from 2017 to 2020 for analysis. The correlation between CDAI and MASLD status, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM) was evaluated by adjusting for confounding variables using weighted binary logistic regression model, linear regression model, and restricted cubic spline (RCS) regression. The median CDAI in this study was - 0.3055 (interquartile range [IQR], - 2.299 to 2.290). The CDAI was higher in the population characterized by being young, female, higher income, absence of diabetes, and non-MASLD. After multivariable adjustment, the results of the weighted linear regression model suggested that higher CDAI may be associated with a decrease in CAP values; the results of the RCS regression model indicated significant non-linear relationships between MASLD status, CAP, LSM, and CDAI. The CDAI corresponding to the inflection points of the relationship curves between MASLD status, CAP, LSM, and CDAI were 0.349, 0.699, and 0.174, respectively. After further stratification by gender, we found that the relationship between MASLD status, CAP, and CDAI was significantly linear for females, whereas for males, it was non-linear, and the CDAI values corresponding to the inflection points in the curves for males were 1.325 and 0.985, respectively. We found that higher CDAI may be associated with decreased CAP values, particularly significant in females, suggesting that the intake of complex dietary antioxidants may ameliorate hepatic steatosis and reduce the occurrence of MASLD. Therefore, promoting dietary patterns rich in antioxidants may be an appropriate strategy to reduce the incidence of MASLD.
Topics: Humans; Male; Female; Antioxidants; Cross-Sectional Studies; Nutrition Surveys; Adult; Middle Aged; Diet; Non-alcoholic Fatty Liver Disease
PubMed: 38877074
DOI: 10.1038/s41598-024-63965-1 -
The Journal of Biological Chemistry Jun 2024Obesity is a major risk factor for liver and cardiovascular diseases. However, obesity-driven mechanisms that contribute to the pathogenesis of multiple organ diseases...
Obesity is a major risk factor for liver and cardiovascular diseases. However, obesity-driven mechanisms that contribute to the pathogenesis of multiple organ diseases are still obscure and treatment is inadequate. We hypothesized that increased glucose-6-phosphate dehydrogenase (G6PD), the key rate-limiting enzyme in the pentose shunt, is critical in evoking metabolic reprogramming in multiple organs and is a significant contributor to the pathogenesis of liver and cardiovascular diseases. G6PD is induced by carbohydrate-rich diet and insulin. Long-term (8 months) high-fat diet (HFD) feeding increased body weight and elicited metabolic reprogramming in visceral fat, liver, and aorta, of the wild-type rats. In addition, HFD increased inflammatory chemokines in visceral fat. Interestingly, CRISPR-edited loss-of-function Mediterranean G6PD variant (G6PD) rats, which mimic human polymorphism, moderated HFD-induced weight gain and metabolic reprogramming in visceral fat, liver, and aorta. The G6PD variant prevented HFD-induced CCL7 and adipocyte hypertrophy. Furthermore, the G6PD variant increased Magel2 - a gene encoding circadian clock-related protein that suppresses obesity associated with Prader-Willi syndrome - and reduced HFD-induced non-alcoholic fatty liver. Additionally, the G6PD variant reduced aging-induced aortic stiffening. Our findings suggest G6PD is a regulator of HFD-induced obesity, adipocyte hypertrophy, and fatty liver.
PubMed: 38876306
DOI: 10.1016/j.jbc.2024.107460 -
Redox Biology Aug 2024α-Ketoglutarate (AKG), a crucial intermediate in the tricarboxylic acid cycle, has been demonstrated to mitigate hyperlipidemia-induced dyslipidemia and endothelial...
α-Ketoglutarate (AKG), a crucial intermediate in the tricarboxylic acid cycle, has been demonstrated to mitigate hyperlipidemia-induced dyslipidemia and endothelial damage. While hyperlipidemia stands as a major trigger for non-alcoholic fatty liver disease, the protection of AKG on hyperlipidemia-induced hepatic metabolic disorders remains underexplored. This study aims to investigate the potential protective effects and mechanisms of AKG against hepatic lipid metabolic disorders caused by acute hyperlipidemia. Our observations indicate that AKG effectively alleviates hepatic lipid accumulation, mitochondrial dysfunction, and loss of redox homeostasis in P407-induced hyperlipidemia mice, as well as in palmitate-injured HepG2 cells and primary hepatocytes. Mechanistic insights reveal that the preventive effects are mediated by activating the AMPK-PGC-1α/Nrf2 pathway. In conclusion, our findings shed light on the role and mechanism of AKG in ameliorating abnormal lipid metabolic disorders in hyperlipidemia-induced fatty liver, suggesting that AKG, an endogenous mitochondrial nutrient, holds promising potential for addressing hyperlipidemia-induced fatty liver conditions.
Topics: Animals; Hyperlipidemias; Mice; Oxidative Stress; Humans; NF-E2-Related Factor 2; AMP-Activated Protein Kinases; Ketoglutaric Acids; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Signal Transduction; Hep G2 Cells; Mitochondria; Male; Lipid Metabolism; Hepatocytes; Fatty Liver; Disease Models, Animal; Liver
PubMed: 38875959
DOI: 10.1016/j.redox.2024.103230 -
Animal Models and Experimental Medicine Jun 2024Apoptosis signal-regulating kinase 1 (ASK1) is a MAP3K kinase in the MAPK signaling pathway activated by stressors and triggers downstream biological effects such as...
BACKGROUND
Apoptosis signal-regulating kinase 1 (ASK1) is a MAP3K kinase in the MAPK signaling pathway activated by stressors and triggers downstream biological effects such as inflammation and apoptosis; therefore, inhibition of ASK1 kinase activity can protect cells from pathological injury. In this study, we designed and synthesized a novel selective ASK1 inhibitor, CS17919, and investigated its pharmacological effects in various animal models of metabolic injury.
METHODS
First, we validated the ability of CS17919 to inhibit ASK1 in vitro and then tested the safety profile of CS17919 in cell lines compared with Selonsertib (GS-4997), a phase III ASK1 inhibitor. We then conducted pharmacokinetic (PK) studies in mice. Finally, we tested the in vivo efficacy of CS17919 in murine models of chronic kidney disease (CKD) and non-alcoholic steatohepatitis (NASH).
RESULTS
Compared to GS-4997, CS17919 demonstrated comparable inhibition of ASK1 in vitro, exhibited lower toxicity, and provided greater protection in palmitic acid-treated LO2 cells. CS17919 also showed pronounced pharmacokinetic properties such as a high plasma concentration. In the unilateral ureteral obstruction model (UUO), CS17919 and GS-4997 preserved kidney function and showed a non-significant tendency to alleviate kidney fibrosis. In the diabetic kidney disease (DKD) model, CS17919 significantly improved serum creatinine and glomerular sclerosis. In the NASH model, the combination of CS17919 and a THRβ agonist (CS27109) was found to significantly improve liver inflammation and substantially reduced liver fibrosis.
CONCLUSIONS
CS17919 showed cell protective, anti-inflammatory, and antifibrotic effects in vitro and in vivo, suggesting its therapeutic potential for metabolic-related kidney and liver diseases.
PubMed: 38873818
DOI: 10.1002/ame2.12437 -
Access Microbiology 2024The novel sudden acute respiratory syndrome coronavirus 2 is an enveloped virus currently causing severe illness and death worldwide. Common antiseptics such as alcohol...
The novel sudden acute respiratory syndrome coronavirus 2 is an enveloped virus currently causing severe illness and death worldwide. Common antiseptics such as alcohol have some efficacy in disinfecting everyday surroundings, but development of more effective disinfectants is imperative. A series of studies focusing on cationic antimicrobials resulted in the development of a safe and effective novel coronavirus disinfectant, DEA-171, which provides ≥99.98 % inhibition of all novel coronavirus variants within 1 min.
PubMed: 38873577
DOI: 10.1099/acmi.0.000631.v5 -
Frontiers in Nutrition 2024Observational studies have found potential associations between dietary intake and multiple sclerosis (MS). However, these associations are inconsistent, and the causal...
OBJECTIVES
Observational studies have found potential associations between dietary intake and multiple sclerosis (MS). However, these associations are inconsistent, and the causal relationship remains unclear. In this study, we aim to examine the causal relationship between genetically predicted dietary composition and the risk and severity of MS using two-sample Mendelian randomization.
METHOD
Genetic instruments for 30 different dietary compositions were extracted from large-scale genome-wide association studies (GWAS), mainly from the UK Biobank dataset. The GWAS data for MS risk and severity were obtained from the International Multiple Sclerosis Genetics Consortium. The primary analysis employed either the inverse variance weighted method or the Wald ratio method to evaluate the causal association. Several sensitivity analyses were also performed.
RESULTS
Genetically predicted higher pork intake was causally associated with an increased risk of MS (odds ratio [OR] = 6.76; = 0.005), while genetically driven higher cereal intake (OR = 0.43, = 0.016), vitamin C supplement (OR < 0.01; = 4.34 × 10), folic acid supplement (OR < 0.01; = 4.91 × 10), and fish oil supplement (OR = 0.04; = 0.017) were causally linked to a decreased risk of MS. In addition, genetically predicted higher alcoholic intake (OR = 1.17; = 0.041) was causally associated with an increase in MS severity, while folic acid supplement (OR < 0.01; = 0.015) was causally linked to a decrease in MS severity.
INTERPRETATION
This study found that increased consumption of cereal, vitamin C, folic acid, and fish oil, coupled with reduced pork and alcohol intake, may potentially decrease the risk and severity of MS. These findings inform the development of dietary-based strategies for MS prevention and treatment.
PubMed: 38873562
DOI: 10.3389/fnut.2024.1410745 -
Food Science & Nutrition Jun 2024Consumer acceptability of beers is influenced by product formulation and processing conditions, which impart unique sensory profiles. This study used multivariate...
Consumer acceptability of beers is influenced by product formulation and processing conditions, which impart unique sensory profiles. This study used multivariate techniques to evaluate at-home consumer sensory acceptability of six commercial beers considering their style, fermentation type, and chemical composition. Samples included top-fermented beers (American India Pale Ale and Stout) and bottom-fermented beers (Pilsner, zero-alcohol Pilsner, Vienna Lager, and Munich Dunkel). Beer consumers ( = 50) conducted sensory hedonic, check-all-that-apply (CATA) and just-about-right (JAR) tests. Chemometric variables included iso-alpha-acids, hordenine, and volatile aromatic compounds, quantified by chromatographic methods, whereas bitterness units (IBU) were determined spectrophotometrically. Lager beers had higher acceptability than top-fermented beer ( < .05) for all attributes. Light-colored beers and medium-height foams had the highest liking scores for visual sensory attributes. Higher concentrations of bitter-tasting molecules, hordenine, and acidity decreased the liking scores of top-fermented (Ale) beers, as a sensory penalty analysis suggested. In contrast, the most favored beers (Pilsners and Munich Dunkel) contained higher fusel alcohol esters linked to fruity aromatic notes. Although a low conversion rate of fatty acids into fruity esters was noted in nonalcoholic Pilsner, its overall liking score was not statistically different from the alcoholic version. However, consumers perceived the nonalcoholic Pilsner as less bitter than its alcoholic counterpart even when IBUs were nonsignificantly different. This study emphasized the significance of understanding beer chemometrics to comprehend consumer acceptability, highlighting the crucial role of bitter molecules. Hence, hordenine, acidity, and volatile contents provided additional and valuable insights into consumer preferences.
PubMed: 38873484
DOI: 10.1002/fsn3.4066 -
Acta Radiologica Open Jul 2024Ingestion of foreign bodies is a rare clinical problem in healthy adults. Less than 1% of cases need surgery due to perforation or obstruction. Here, we describe an...
Ingestion of foreign bodies is a rare clinical problem in healthy adults. Less than 1% of cases need surgery due to perforation or obstruction. Here, we describe an unusual case of a wine-cork ingestion by a 54-year-old woman with a history of chronic alcohol consumption. Computed tomography (CT) of the abdomen and pelvis revealed foreign body (FB) in terminal ileum. The proximal part of the ileum was dilated due to obstruction. Laparotomy was performed, and the FB was removed without complications. Most ingested FBs spontaneously pass through the gastrointestinal tract. However, in rare instances, the FB can cause obstruction. In case of suspicion of serious complications such as obstruction and perforation, abdominopelvic CT should be used. The application of radiographic techniques in the identification of FBs and the assessment of potential complications plays a crucial role in expediting medical interventions for patients.
PubMed: 38873433
DOI: 10.1177/20584601241258686