Search Results (469)

Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the HSD17B10 gene product. It plays an appreciable part in the carcinogenesis and pathogenesis of neurodegeneration, such as Alzheimer’s disease and infantile neurodegeneration. This mitochondrial, homo-tetrameric protein is a central hub in various metabolic pathways, e.g., branched-chain amino acid degradation and neurosteroid metabolism. It can bind to other proteins carrying out diverse physiological functions, e.g., tRNA maturation. It has also previously been proposed to be an Aβ-binding alcohol dehydrogenase (ABAD) or endoplasmic reticulum-associated Aβ-binding protein (ERAB), although those reports are controversial due to data analyses. For example, the reported k_m value of some substrate of ABAD/ERAB was five times higher than its natural solubility in the assay employed to measure k_m. Regarding any reported “one-site competitive inhibition” of ABAD/ERAB by Aβ, the k_i value estimations were likely impacted by non-physiological concentrations of 2-octanol at high concentrations of vehicle DMSO and, therefore, are likely artefactual. Certain data associated with ABAD/ERAB were found not reproducible, and multiple experimental approaches were undertaken under non-physiological conditions. In contrast, 17β-HSD10 studies prompted a conclusion that Aβ inhibited 17β-HSD10 activity, thus harming brain cells, replacing a prior supposition that “ABAD” mediates Aβ neurotoxicity. Furthermore, it is critical to find answers to the question as to why elevated levels of 17β-HSD10, in addition to Aβ and phosphorylated Tau, are present in the brains of AD patients and mouse AD models. Addressing this question will likely prompt better approaches to develop treatments for Alzheimer’s disease. Full article

Alcohol is a prevalent psychoactive substance and a risk factor for developing injuries and non-communicable diseases, representing a significant health and economic burden. Alcohol involves numerous molecular pathways. Its metabolism is regulated by alcohol dehydrogenases and aldehyde dehydrogenases; it also stimulates cholinergic interneurons, increasing the sensitivity of 5-HT3 receptors, while chronic alcohol consumption alters the mesolimbic dopaminergic system involved in reward processing. The treatment of alcohol use disorder (AUD) is essential to manage complex patients, following an evidence-based approach. The aim of this narrative review is to provide a clear and practical summary to support and assist healthcare professionals in the Italian context. Approved pharmacological treatments for AUD include oral naltrexone and acamprosate, sodium oxybate, disulfiram, and nalmefene. Off-label therapies include baclofen, topiramate, gabapentin, pregabalin, ondansetron, and cytisine. A more informed clinical and practical approach that understands the altered neuronal signaling pathways is essential for offering effective, efficient, appropriate, and safe therapeutic algorithms for complex patients with alcohol use disorder. A comprehensive framework should include integrated treatments with a personalized approach. Full article

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

The market value of litchi fruit is declining quickly due to its susceptibility to disease and rapid pericarp browning. Slightly acidic electrolyzed water (SAEW) treatment is recognized as a safe disinfection technology that not only preserves the quality of postharvest produce, but also enhances disease resistance. This study assessed the efficacy of SAEW in preserving litchi fruit and boosting its resistance to disease. Litchi fruit underwent treatment with SAEW at various available chlorine concentrations (ACC) (10, 25, 50, and 75 mg/L) and subsequently stored at 25 °C for a duration of six days. The results revealed that SAEW with an ACC of 25 mg/L markedly improved the postharvest quality of litchi fruits, reduced disease incidence, and enhanced the appearance of the pericarp and nutrient levels in the arils. Additionally, this treatment enhanced the levels of disease resistance-related compounds, including lignin, flavonoids, and total phenolics, in the pericarp of litchis during the later storage stages (p < 0.05). Furthermore, in the final three days of storage, there were also noticeable increases (p < 0.01) in the activities of pericarp disease resistance enzymes (DREs), such as phenylalanine ammonialyase, cinnamate-4-hydroxylase, 4-coumarate CoA ligase, cinnamyl alcohol dehydrogenase, peroxidase, polyphenol oxidase, chitinase, and β-1,3-glucanase. Based on these results, it was concluded that SAEW triggered DRE activities and increased the accumulation of disease resistance-related compounds by regulating the phenylpropane pathway to suppress disease development, and elevated the storage quality of harvested litchi fruit. Consequently, SAEW has proven to be an effective and safe method for enhancing the storability of litchi fruit. Full article

Class III alcohol dehydrogenase (ADH3), primarily localized in the liver and kidney, contributes to alcohol metabolism during chronic alcohol consumption (CAC). However, its role in kidney function remains unclear. This study investigated renal morphological changes associated with ADH3-mediated alcohol metabolism. Nine-week-old male wild-type (WT) and ADH3-deficient (Adh3^-/-) mice were administered 10% ethanol for 1 month. Histological analyses were performed using periodic acid–Schiff (PAS) staining and electron microscopy. Serum biochemical parameters were also assessed. In WT mice, CAC induced an increase in cuboidal parietal epithelial cells (PECs) in Bowman’s capsule, along with elevated testosterone levels in both serum and urine. Adh3^-/- mice showed increased PECs even in the control group, with similarly elevated serum testosterone in both control and ethanol-treated groups. These findings suggest that ADH3 is involved in testosterone metabolism, and that that metabolism is suppressed by CAC because ADH3 shifts toward ethanol metabolism. The resulting testosterone elevation may contribute to PEC proliferation. An increase in PECs observed even in Adh3^-/- control mice may also be caused by the lack of testosterone metabolism via ADH3. Thus, renal ADH3 may protect kidney structure through testosterone metabolism, but its role may be disturbed by CAC. This study highlights the role of ADH3 in the relationship between physiological steroid metabolism and alcoholic pathological abnormality in the kidney. Full article

European plum (Prunus domestica) is among the most important stone fruits cultivated worldwide. However, its production is significantly affected by fungal brown rot disease, caused by Monilinia spp. pathogens, which threaten the crop throughout the entire vegetation period. This study aimed to visually assess brown rot resistance and susceptibility in European plum and to perform whole-genome sequencing (WGS) of selected cultivars and hybrids grown in Lithuania, with the goal of identifying candidate single-nucleotide polymorphisms (SNPs) associated with disease response. WGS was performed for 20 European plum cultivars and hybrids with known resistance or susceptibility profiles, generating over 1,4 million SNPs. These SNPs were filtered to identify genetic variants associated with brown rot disease. Three candidate SNPs were found to be significantly associated with disease response (located on chromosomes G5 and G8) and one linked to susceptibility (on chromosome G5). Identified SNPs were located in genes encoding alcohol dehydrogenase family enzymes (resistant cultivars, G5 chromosome) and beta-glucosidase family enzymes (variants found in both resistant and susceptible cultivars, G5 chromosome), which are important for plant biotic stress response. The findings of this study provide a valuable foundation for the development of molecular markers for identifying resistant and susceptible cultivars and may inform future European plum breeding programs. 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

Excessive drinking or even alcoholism poses noticeable health risks to society, and investigating ways to improve alcohol metabolism may be a potential strategy to address this public health issue. The aim of this study was to explore the efficacy of freshwater clam aqueous extract (CE) in promoting alcohol metabolism and to further elucidate its potential mechanism. Male Wistar rats were divided into four groups: (1) control group (C); (2) vehicle group (V), which was given a single dose of 2 g/kg bw ethanol; (3) low-dose CE group (CEL), which was given ethanol and 128 mg/kg bw CE; and (4) high-dose CE group (CEH), which was given ethanol and 256 mg/kg bw CE. Blood was drawn from the tails of the rats at 0, 1, 2, 3, and 4 h after alcohol administration, and serum samples were collected. The results showed that compared with the V group, oral administration of CE reduced the ethanol concentration in the serum of the rats, with the area under the serum ethanol curve (AUC) of the CEH group decreased by 32.6%, exhibiting a significant difference (p < 0.05). Moreover, the high-dose CE (CEH) treatment significantly increased the activities of alcohol dehydrogenase (ADH), acetaldehyde dehydrogenase (ALDH), catalase (CAT), and superoxide dismutase (SOD) in the liver of the rats by 41.5%, 42.4%, 40.6%, and 34.6%, respectively, compared with those in group V (p < 0.05). The Western blot results indicated that CE reduced the expression of ethanol-induced inflammation-related proteins COX-2, iNOS, and TNF-α in the liver by 66.4%, 90.6%, and 41.4%, respectively. In conclusion, it can be inferred that CE can help reduce the ethanol concentration in the serum of rats fed with alcohol, and its possible mechanism is to promote the metabolism of ethanol by increasing the activities of ADH and ALDH and the antioxidant capacity in the liver. Full article

Industrial biotechnology offers a potential ecological solution for PET recycling under relatively mild reaction conditions via enzymatic degradation, particularly using the leaf branch compost cutinase (LCC) quadruple mutant ICCG. To improve the efficient downstream processing of this biocatalyst after heterologous gene expression with a suitable production host, protein crystallization can serve as an effective purification/capture step. Enhancing protein crystallization was achieved in recent studies by introducing electrostatic (and aromatic) interactions in two homologous alcohol dehydrogenases (Lb/LkADH) and an ene reductase (NspER1-L1,5) produced with Escherichia coli. In this study, ICCG, which is difficult to crystallize, was utilized for the application of crystal contact engineering strategies, resulting in ICCG mutant L50Y (ICCGY). Previously focused on the Lys-Glu interaction for the introduction of electrostatic interactions at crystal contacts, the applicability of the engineering strategy was extended here to an Arg-Glu interaction to increase crystallizability, as shown for ICCGY T110E. Furthermore, the rationale of the engineering approach is demonstrated by introducing Lys and Glu at non-crystal contacts or sites without potential interaction partners as negative controls. These resulting mutants crystallized comparably but not superior to the wild-type protein. As demonstrated by this study, crystal contact engineering emerges as a promising approach for rationally enhancing protein crystallization. This advancement could significantly streamline biotechnological downstream processing, offering a more efficient pathway for research and industry. Full article

Lodging imposes substantial constraints on maize yield potential and agronomic efficiency, critically undermining productivity and resource optimization in cultivation systems. This study aimed to elucidate the mechanism whereby ethephon enhances lodging resistance and analyze the sensitivity differences to ethephon among distinct maize inbred lines. Through exogenous application of ethephon (200 and 400 mg/L, S1 and S2 treatments) to four classic maize inbred lines (Zheng58, Chang7-2, PH6WC, and PH4CV), we systematically evaluated its effects on plant morphology, stalk biomechanical properties, and lignin biosynthesis. Results demonstrated that ethephon optimized plant morphology through reductions in plant height, ear height, leaf area, leaf angle, and internode length. Significant augmentations in stalk bending resistance (a maximum increase of 52.61% in PH4CV) and puncture strength (most pronounced in Zheng58) were mechanistically associated with increased lignin content and enhanced activity of key biosynthetic enzymes [cinnamyl alcohol dehydrogenase (CAD), phenylalanine ammonia-lyase (PAL), and 4-coumarate-CoA ligase (4CL)], with PH6WC exhibiting the most robust enzymatic response. These findings underscored genotype-specific regulatory effects of ethephon, bridging the knowledge gap regarding its molecular–physiological interplay with maize genotypes. The study provides critical insights for precision breeding and optimization strategies employing plant growth regulators to improve maize lodging resistance. 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

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

Erythritol has been widely used in the food industry, which predominantly synthesizes it via microbial fermentation, in which Yarrowia lipolytica serves as the preferred candidate chassis strain. However, the wild-type strain of Y. lipolytica exhibits several limitations, including suboptimal industrial performance and elevated levels of by-products, which pose significant challenges in biomanufacturing processes. It is significant to understand the synthesis mechanism of erythritol for improving the capacity of erythritol production by Y. lipolytica. In this study, a mutant exhibiting high erythritol production and stable genetic performance was obtained via a combination of UV and atmospheric and room-temperature plasma mutagenesis. Some key genes related to erythritol production were identified through comparative transcriptome analysis of the mutant strain, revealing significant changes in their expression levels. Individual overexpression of the genes encoding ribose-5-phosphate isomerase, glucose-6-phosphate-1-epimerase, adenylate kinase, and alcohol dehydrogenase in Y. lipolytica Po1g enhanced erythritol production, demonstrating the critical role of each gene in erythritol production. This finding elucidates the molecular mechanism underlying the improved erythritol yield in the mutant strain. The Y. lipolytica mutant C1 produced 194.47 g/L erythritol in a 10 L fermenter with a productivity of 1.68 g/L/h during batch fermentation, surpassing the wild-type strain and reducing the cultivation time by 21 h. It is significant to understand the mechanism of erythritol synthesis for improving erythritol production and its application in industrial-scale production. Full article

Lignocellulosic biomass is widely recognized as a renewable resource for bioconversion. However, the presence of inhibitors such as furfural, 5-HMF, and acetic acid can inhibit cell growth, thereby affecting the overall efficiency of the bioconversion process. The studies on the degradation of lignocellulosic hydrolysate inhibitors by Saccharomyces cerevisiae have been limited. In this research, a yeast strain Kodamaea ohmeri can degrade inhibitors furfural, 5-HMF, and acetic acid, and the genome sequence of the strain was analyzed. Furthermore, the molecular detoxification mechanism of K. ohmeri SSK against lignocellulosic hydrolysate inhibitors was predicted using whole genome sequencing. Annotation based on the COG/KEGG databases identified 57 key detoxification genes, including the alcohol dehydrogenase (ADH) gene, aldo-keto/aldehyde reductase (AKR/ARI) gene, and aldehyde dehydrogenase (ALDH) gene. Stress tolerance experiments revealed that the maximum tolerance concentration for the strain was 5.2 g/L of furfural, 2.5 g/L of 5-HMF, and 5.9 g/L of acetic acid, respectively. A NAD(P)⁺-dependent bifunctional enzyme with possible ADH and ARI activities was found by conserved domain analysis. Phylogenetic analysis indicated that this enzyme shared 99% homology with the detoxification enzyme from S. cerevisiae S288C (GenBank: Q04894.1). This study represents the first comprehensive analysis of the inhibitor detoxification network in K. ohmeri SSK from a genome perspective, providing theoretical targets and design strategies for developing highly efficient biorefinery strains. Full article