Search Results (362)

Background: Modulating ethanol metabolism and attenuating alcohol-induced oxidative stress are promising therapeutic strategies for reducing the severity of hangovers and alleviating their associated physiological burden. Methods: A randomized, double-blind, placebo-controlled, crossover study was conducted to evaluate the effects of the probiotic strain Leuconostoc mesenteroides VITA-PB2 on ethanol metabolism, oxidative stress, and hangover-related symptoms in 28 healthy adults. The participants consumed either VITA-PB2 or a placebo before standardized alcohol intake, with a 7-day washout period and subsequent crossover. Primary outcomes included blood ethanol, acetaldehyde levels, and aldehyde dehydrogenase (ALDH) activity. Secondary outcomes measured hangover severity assessed by the Acute Hangover Scale (AHS), liver enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT), oxidative stress indicators reactive oxygen species (ROS) and nitric oxide (NO), and antioxidant responses measured by glutathione peroxidase (GPx), catalase, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity. Results: VITA-PB2 supplementation led to a sustained reduction in blood ethanol concentrations beginning at 0.5 h post-ingestion compared with the placebo group, indicating more efficient ethanol clearance. Additionally, VITA-PB2 significantly reduced acetaldehyde levels at 1 h post-ingestion (p < 0.05) and increased ALDH activity by 42.15% at 30 min (p < 0.05). It also markedly reduced ROS levels at 1 h (p < 0.05), enhanced glutathione peroxidase (GPx) activity at 2 h (p < 0.01), and significantly improved the subjective hangover symptoms, particularly thirst (p < 0.05). Conclusions: No adverse effects were reported during the trial, indicating that Leuconostoc mesenteroides VITA-PB2 is a safe probiotic. These findings suggest its efficacy in mitigating alcohol-induced oxidative stress and alleviating hangover-related symptoms. Full article

Colletotrichum capsici is an important pathogen causing anthracnose in postharvest peppers in parts of Asia, seriously compromising quality and storage life. Unveiling the pathogenic mechanism can better prevent postharvest disease in pepper. This study investigated the impacts of C. capsici infection on cell wall and phenylpropanoid metabolism in postharvest pepper. Compared to the non-inoculated peppers, C. capsici infection notably increased the disease index, damaged visual quality, and reduced the firmness. Morphological observations showed that C. capsici infection contributed to the collapse of epidermal cell structure. During the early stage, C. capsici triggered pepper’s defensive responses, including lignin deposition around the wounds, increased cellulose and hemicellulose content, and boosted disease-resistance enzymes, including phenylalanine ammonia-lyase (PAL), cinnamic acid 4-hydroxylase (C4H), 4-coumarate-CoA ligase (4CL), cinnamyl alcohol dehydrogenase (CAD), laccase (LAC), β-1,3-glucanase (β-1,3-Glu), and chitinase (CHI), alongside elevated total phenolics and flavonoids. However, as storage time progressed, the activities of carboxymethy cellulase (Cx), polygalacturonase (PG), pectin methylesterase (PME), and β-glucosidase (β-Glu) remained at a high level, leading to a reduction in cell wall components, a decline in the activities of disease-resistance enzymes, and a decrease in phenylpropanoid metabolite, resulting from disease progression in pepper. These insights highlight the need for early intervention strategies to mitigate postharvest losses by targeting pathogen-induced stress responses and cell wall integrity preservation. Full article

Despite the growing morbidity associated with alcohol use disorder (AUD), current FDA-approved therapeutics fail to adequately address the condition. This is in part due to the complex systemic effects of ethanol (EtOH), which have particularly negative consequences on the gut–liver–brain axis. Importantly, two systemic mechanisms underlying the progression of AUD remain underemphasized in therapeutic development: thiamine deficiency and neuroinflammation. Alcohol-induced thiamine deficiency leads to reduced activity of key metabolic enzymes, thereby resulting in energy deficits, oxidative stress, and severe clinical implications. EtOH also activates TLR4 and NLRP3, both of which play critical roles in the regulation of neuroimmune responses. While research directly investigating the relationship between thiamine deficiency and neuroinflammation is still in its early stages, our review highlights the emerging connections between these two seemingly distinct pathomechanisms. Additionally, potential therapeutic approaches and targets for addressing AUD at a systemic level are discussed. Full article

Background/Objectives: Non-alcoholic steatohepatitis (NASH) carries a high risk of developing hepatic fibrosis. Hugan tablets (HGTs), a traditional Chinese medicine, have exhibited potent anti-hepatic fibrosis effects, though the underlying mechanisms remain unclarified. This study aims to assess the efficacy of HGTs against NASH-related liver fibrosis in mice and investigate the underlying mechanisms via the integration of pseudotargeted metabolomics and microbiomics. Methods: C57BL/6 mice were fed a choline-deficient, ethionine-supplemented (CDE) diet and treated with HGTs. The therapeutic effects of HGTs in CDE mice were assessed. The underlying mechanism of HGTs was investigated by the integration of microbiomics, a pseudo-sterile model, untargeted followed by pseudotargeted metabolomics, and molecular docking. Results: HGTs alleviated NASH-related hepatic fibrosis in CDE mice and restored the composition of the gut microbiota. The depletion of the gut microbiota eliminated the anti-hepatic fibrosis effect of HGTs. HGTs increased intestinal 7-ketolithocholic acid and tauroursodeoxycholic acid via 7α/β-hydroxysteroid dehydrogenase (7α/βHSDH), while reducing deoxycholic acid (DCA) and taurodeoxycholic acid through inhibition of bile acid 7α-dehydratase (BaiE), leading to lower hepatic DCA. Six intestinal components of HGTs interacted with 7αHSDH, 7βHSDH, and BaiE, which are expressed in the bacterial genera altered by HGTs. Conclusions: HGTs alleviate NASH fibrosis by reshaping the gut microbiome, acting on microbial BA-metabolizing enzymes, and regulating the BA metabolism in the liver and gut. Full article

Photosynthetic organisms such as cyanobacteria have the potential for the sustainable production of complex organic molecules due to their ability to use light as an energy source to fix CO₂ and assimilate inorganic nutrients. Over the past decade, large efforts have been put into the metabolic engineering of cyanobacteria to produce various compounds such as alcohols, isoprenoids, biopolymers, and recombinant proteins. Forskolin is a structurally complex labdane-type diterpenoid with eight chiral carbon atoms and is naturally produced in the root cork of the plant Plectranthus barbatus. Forskolin is a potent cAMP activator indicated as a pharmaceutical for a variety of diseases. In the plant, forskolin biosynthesis from geranylgeranyl diphosphate involves six enzymes: two terpene synthases, three cytochrome P450s, and a single acetyltransferase. In this work, we express all six biosynthetic genes from Plectranthus barbatus in Synechocystis sp. PCC. 6803 and demonstrate heterologous production of this complex diterpenoid in a phototroph cyanobacterium. Forskolin titers reached 25.0 ± 4.4 µg/L and the forskolin was entirely secreted into the media. The forskolin-producing Synechocystis strain and empty vector control were cultivated in a photobioreactor for 8 days. Both strains showed similar chlorophyll a contents, and the forskolin-producing strain reached a slightly higher OD₇₃₀ than the control. Forskolin began accumulating in the supernatant after 4 days and increased over time. These results indicate that forskolin production did not negatively impact cell growth. Full article

Aroma is an important processing and consumption quality trait of fruits and vegetables, and terpenes produced from the terpenoid metabolic pathway are a critical component of chili fruit flavor. This pathway involves the participation of at least eighteen enzymes, such as AACT, HMGS, HMGR, MVK, PMK, MVD, FPPS, GGPPS, DXS, DXR, MCT, CMK, MECPS, HDS, HDR, GPPS, IDI, and TPS. In this study, the genome wide information, expression characteristics, and relationship with terpenoids of terpenoid pathway genes are analyzed in C. annuum. The results showed that C. annuum has sixty-seven genes related to terpene metabolic pathways. Non-targeted metabolomics studies found that the content of aromatic terpenoids α-calacorene, α-cubene, and cis-β-farnesene increased with fruit development in HDL fruits, while linalool and nerolidol were much higher in GLD608. Correlation analyses between qRT-PCR and metabolome data showed that the expression levels of CaHMGS-3, CaMVD-1, CaCMK-1, and CaGGPPS-2 were positively correlated with the content of linalool, a flavor monoterpene alcohol. CaMECPS-1 was positively correlated with cis-β-farnesene, and there was also a significant positive regulatory relationship between CaTPS-5 and nerolidol relationship. In conclusion, the present study provides genetic resources for further studies on the gene regulatory mechanisms of flavor synthesis and terpenoid metabolic pathways in chili. Full article

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic liver disease linked to obesity and diabetes. This study aimed to assess whether serum GOT and GPT can predict NAFLD early in at-risk individuals. A retrospective cohort study was conducted using hospital records from the University of Debrecen (2012–2022), including 4886 NAFLD-free individuals at baseline. NAFLD incidence was tracked using ICD-10 codes, with transaminase levels (GOT and GPT) and key metabolic comorbidities analyzed as predictors in a longitudinal design. Survival analysis included Fleming–Harrington tests, Kaplan–Meier, and Nelson–Aalen estimators as well as restricted mean survival time. The Royston–Parmar flexible parametric model was used to assess the time-dependent effects of GOT, GPT, and metabolic risk factors on NAFLD incidence. An elevated GOT was significantly associated with an increased NAFLD hazard (HR = 2.71, 95% CI: 1.31–5.58), as was an elevated GPT (HR = 2.21, 95% CI: 1.09–4.43). Disorders of lipid metabolism showed the strongest association (HR = 3.29, 95% CI: 1.51–7.25). Elevated GOT and GPT levels, in combination with demographic and clinical factors, may serve as valuable prognostic biomarkers for NAFLD progression, underscoring the importance of routine liver enzyme monitoring and comprehensive metabolic management to improve long-term patient outcomes. Full article

Background and Aims: Non-alcoholic beers (NABs) are gaining popularity as alternatives to alcoholic beverages, yet their metabolic and health effects compared to no consumption of these drinks remain unclear. Material and Methods: The investigator-blinded, single-center, randomized study compares the effects on the metabolism, health, and gut microbiome of the daily consumption of different NABs—pilsener, mixed beer, and wheat beer—on glucose and fat metabolism, body composition, and liver function in 44 healthy young men. The participants consumed 660 mL of one of these beers or water daily for 4 weeks. We measured indicators of glucose and lipid metabolism, liver enzymes, body composition, and the composition of the gut microbiota. Results: The findings revealed that mixed beer increased fasting glucose and triglycerides, and wheat beer increased insulin, C-peptide, and triglycerides. The intake of pilsener and water decreased cholesterol and LDL levels without significantly affecting glucose metabolism. Biomarkers of liver damage such as M30 lowered in water and pilsener, while ALT and AST lowered in mixed beer. The pattern of the gut microbiota also changed, as pilsener lowered Firmicutes and increased Actinobacteria. Conclusions: In summary, consumption of NABs, especially mixed and wheat beers, exerts an unfavorable metabolic impact on glucose and fat, while pilsener and water are more favorable from a metabolic perspective. We concluded that the metabolic alterations seen are probably due to the caloric and sugar content in NABs, rather than polyphenols. The chronic effects of NABs on health should be evaluated in future studies. Full article

Background/Objectives: The present study aims to evaluate the anti-hangover and hepatoprotective activities of the leaf extract of T. laurifolia in experimental animals. Methods: Two experiments were conducted that involved giving a single dose of the leaf extract of T. laurifolia (1, 10, or 100 mg/kg body weight) to rats 30 min either before or after administration of 40% ethanol (5 g/kg body weight). The locomotor activity of the rats was measured before and after receiving the test substances. Blood samples were collected to determine the ethanol, acetate, and liver enzyme levels. Liver tissues were collected to evaluate alcohol-metabolizing enzymes, antioxidant enzyme activities, and antioxidant levels. Results: Administration of the leaf extract of T. laurifolia to the rats prior to ethanol increased locomotor activity and reduced blood ethanol levels. The extract also prevented changes in liver enzyme levels and demonstrated antioxidant activity by scavenging free radicals resulting from ethanol-induced oxidative stress. Conversely, rats administered the leaf extract of T. laurifolia after receiving ethanol were able to reduce the elevated liver enzyme levels back to normal levels, and probably helped to inhibit the harmful effects of free radicals by stimulating the synthesis and/or activities of antioxidant enzymes. Administration of the leaf extract of T. laurifolia either before or after ethanol exposure was able to reduce the activity of an alcohol-metabolizing enzyme as well as reduce blood acetate levels. Conclusions: In summary, receiving the leaf extract of T. laurifolia before alcohol consumption could probably help to reduce hangover symptoms and was shown to have hepatoprotective effects superior to receiving the extract after alcohol consumption. Full article

Background/Objective: The prevention and treatment of alcoholic liver disease (ALD) urgently require safe and effective nutritional intervention strategies. Polyphenol extracts from sugarcane molasses (SP) show antioxidant and anti-inflammatory potential, yet their protective effects against ALD have not been elucidated. This study explored the therapeutic potential of SP in alcohol-induced chronic liver damage. Methods: A graded alcohol concentration-induced liver damage model was established in C57BL/6J mice to systematically evaluate SP’s regulatory effects on liver function markers, lipid metabolism, oxidative stress indicators, inflammatory factors, and related molecular mechanisms through a 10-week nutritional intervention. Results: The results demonstrated that SP intervention significantly inhibited the liver index, alanine aminotransferase and aspartate aminotransferase activities, and triglyceride and total cholesterol accumulation in mice. SP enhanced antioxidant enzyme activities in a dose-dependent manner, with the high-dose group increasing catalase activity by 161.19% and superoxide dismutase activity by 22.97%. Furthermore, SP significantly reduced the levels of pro-inflammatory cytokines, including interleukin-1β, interleukin-6, and tumor necrosis factor-α, thereby alleviating hepatic inflammatory infiltration. Mechanistic studies revealed that SP effectively mitigated alcohol-induced oxidative stress and inflammatory injury by inhibiting cytochrome P450 2E1 overexpression, regulating the Kelch-like ECH-associated protein 1 signaling pathway, and suppressing nuclear factor-kappa B pathway activation. Conclusions: The findings reveal that SP mitigates ALD via synergistic antioxidant and anti-inflammatory mechanisms, providing a novel strategy for high-value utilization of sugarcane molasses byproducts in agricultural industries. Future studies should focus on the contribution of the different phenolics in SP and validate their specific hepatoprotective mechanisms. Full article

Background/Objectives: Lumbosacral spinal stenosis (LSS) is a degenerative condition characterized by narrowing of the spinal canal and associated neuropathic pain. While mechanical compression is well-characterized, the molecular mechanisms contributing to symptom severity remain poorly understood. Neurturin (NRTN), a member of the glial cell line-derived neurotrophic factor family, has emerged as a potential mediator of neural plasticity and nociception, but its role in spinal stenosis is largely unexplored. Methods: We analyzed NRTN mRNA and protein expression in ligamentum flavum samples from 96 patients undergoing surgery for LSS and 85 non-degenerative postmortem controls. Quantification was performed using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry. Pain severity Visual Analog Scale (VAS), body mass index (BMI), diabetes, smoking, and alcohol use were assessed as modulators of NRTN expression. Results: NRTN expression was significantly elevated in LSS patients versus controls at both transcript and protein levels (p < 0.05). NRTN levels positively correlated with pain intensity (VAS; ANOVA p = 0.032 for mRNA, p = 0.041 for protein). Multivariate regression identified BMI (β = 0.50, p = 0.015) and diabetes (β = 0.39, p = 0.017) as independent predictors of increased NRTN expression. Alcohol use also showed a positive association (p = 0.046), while smoking showed no significant independent effect. Conclusions: Neurturin is upregulated in ligamentum flavum tissue from LSS patients and correlates with pain severity and metabolic risk factors. These findings suggest NRTN as a potential biomarker and therapeutic target in degenerative spine disease. Further longitudinal and mechanistic studies are warranted to elucidate its role in chronic pain and neuroinflammation. Full article

α-ketoglutarate dehydrogenase complex (KGDHc) is a crucial enzyme in the tricarboxylic acid (TCA) cycle that intersects monosaccharides, amino acids, and fatty acid catabolism with oxidative phosphorylation (OxPhos). A key feature of KGDHc is its ability to sense changes in the redox environment through the reversible oxidation of the vicinal lipoic acid thiols of its dihydrolipoamide succinyltransferase (DLST; E2) subunit, which controls its activity and, by extension, OxPhos. This characteristic inculcates KGDHc with redox regulatory properties for the modulation of metabolism and mediating of intra- and intercellular signals. The innate capacity of KGDHc to participate in the regulation of cell redox homeodynamics also occurs through the production of mitochondrial hydrogen peroxide (mtH₂O₂), which is generated by the dihydrolipoamide dehydrogenase (DLD; E3) downstream from the E2 subunit. Reversible covalent redox modification of the E2 subunit controls this mtH₂O₂ production by KGDHc, which not only protects from oxidative distress but also modulates oxidative eustress pathways. The importance of KGDHc in modulating redox homeodynamics is underscored by the pathogenesis of neurological and metabolic disorders that occur due to the hyper-generation of mtH₂O₂ by this enzyme complex. This also implies that the targeted redox modification of the E2 subunit could be a potential therapeutic strategy for limiting the oxidative distress triggered by KGDHc mtH₂O₂ hyper-generation. In this short article, I will discuss recent findings demonstrating KGDHc is a potent mtH₂O₂ source that can trigger the manifestation of several neurological and metabolic diseases, including non-alcoholic fatty liver disease (NAFLD), inflammation, and cancer, and the targeted redox modification of the E2 subunit could alleviate these syndromes. Full article

Background: Chronic liver disease (CLD) is a major global health concern, contributing significantly to morbidity and mortality. Cirrhosis and liver cancer are the leading causes of liver-related deaths, with various etiological factors, such as metabolic disorders and alcohol-related and viral hepatitis, driving its global prevalence. Non-invasive biomarkers and scoring systems have emerged as key tools for assessing liver disease severity and differentiating CLD from cirrhosis. This study evaluates biomarkers and non-invasive scores and their utility in distinguishing CLD from cirrhosis. Methods: This retrospective observational study included 250 adult patients hospitalized between January 2021 and December 2023 at Cluj County Emergency Clinical Hospital, Romania. Patients were diagnosed with either cirrhosis or CLD of viral, autoimmune, or primary biliary cholangitis (PBC) etiology. Non-invasive biomarkers, scores, and various hemogram-derived ratios were evaluated. Statistical analysis involved descriptive statistics, comparative tests, and receiver operating characteristic (ROC) curve analysis. Results: Among the 250 patients, 137 had liver cirrhosis (54.8%) and 113 had CLD without cirrhosis (45.2%). Significant differences were observed in laboratory parameters, with cirrhosis patients showing lower hemoglobin, platelet count, and albumin levels alongside higher liver enzymes and INR values. Non-invasive scores such as APRI, FIB-4, and NFS demonstrated higher values in the cirrhosis group, indicating more advanced liver damage. Hemogram-derived ratios, particularly the neutrophil-to-lymphocyte ratio (NLR), were higher in cirrhosis patients. ROC analysis revealed that the Lok index had the highest discriminatory power (AUC 0.89), followed by the King score (AUC 0.864) and the Fibrosis index (AUC 0.856), which effectively distinguished cirrhosis from CLD. Conclusions: This study underscores the utility of non-invasive biomarkers and scoring systems in differentiating CLD from cirrhosis. The Lok index, King score, and Fibrosis index demonstrated excellent diagnostic accuracy, while hemogram-derived ratios, such as NLR, offer insights into systemic inflammation associated with liver disease progression. These findings support the integration of non-invasive markers into clinical practice for improved risk stratification and management of liver diseases. Full article

Plant glutathione peroxidase-like (GPXL) enzymes are thiol-based peroxidases that reduce H₂O₂ or hydroperoxides to water or alcohols using electrons principally from thioredoxin. Arabidopsis thaliana possesses eight isoenzymes (AtGPXL1−8) located in different plant organelles and have various roles in redox-dependent processes. The determination of the redox potential of 6-day-old T-DNA insertional mutants (Atgpxl1–Atgpxl8) using a cytosolic redox-sensitive fluorescent probe (roGFP2) uncovered more oxidized redox status in the shoot and/or root of the untreated mutants, except for Atgpxl5. To investigate the involvement of AtGPXLs in the growth and abiotic stress responses of seedlings, the 4-day-old Atgpxls were exposed to salt and osmotic stresses for two weeks. The evaluation of the reactive oxygen species (ROS) levels of untreated 18-day-old plants using fluorescent microscopy revealed the elevated accumulation of total ROS in the shoots and, in some cases, the roots of the mutants. Regarding the growth of roots, both the length of primary roots and/or the number of lateral roots were affected by the mutation of AtGPXLs. A strong negative correlation was observed between the ROS level of wild type shoots and the development of lateral roots, but it was altered in mutants, while in the case of Atgpxl1, Atgpxl5, and Atgpxl7 seedlings, it disappeared; in other mutants (Atgpxl4, Atgpxl6, and Atgpxl8), the correlation became stronger. Our analysis underpins the discrete role of AtGPXL enzymes in controlling the growth and development of plants by fine tuning the ROS contents and redox status in an organ-specific way. Differences in root phenotype and metabolic activity between Atgpxl mutants and wild type plants highlight the essential role of AtGPXLs in ROS processing to support growth, which is particularly evident when one GPXL isoenzyme is absent or its activity is reduced, both under normal and abiotic stress conditions. Full article

The present pilot study aimed to investigate whether common single nucleotide polymorphisms (SNPs) in the gene encoding glutathione S-transferase omega 1 (GSTO1), both individually and in combination with variants of the catalytic subunit of the glutamate cysteine ligase (GCLC) gene and environmental risk factors, are associated with the risk of psoriasis. The research included a total of 944 participants, comprising 474 individuals diagnosed with psoriasis and 470 healthy control subjects. Five common SNPs in the GSTO1 gene—specifically, rs11191736, rs34040810, rs2289964, rs11191979, and rs187304410—were genotyped in the study groups using the MassARRAY-4 system. The allele rs187304410-A (OR = 0.19, 95% CI 0.04–0.86, Pperm = 0.02) and the genotype rs187304410-G/A (OR = 0.19, 95% CI 0.04–0.85, Pperm = 0.01) were found to be associated with psoriasis in females. The model-based multifactor dimensionality reduction approach facilitated the identification of higher-order epistatic interactions between the variants of the GSTO1 and GCLC genes (Pperm < 0.0001). These interactions, along with the risk factor of alcohol abuse, collectively contribute to the pathogenesis of psoriasis. This study is the first to demonstrate that polymorphisms in the GSTO1 gene, both individually and in combination with variants of the GCLC gene and alcohol abuse, are associated with an increased risk of psoriasis. Full article