Search Results (155)

Acetic acid bacteria (AAB, family Acetobacteraceae) are obligate aerobic microorganisms characterized by a highly efficient oxidative metabolism driven by membrane-bound dehydrogenases. Their ability to incompletely oxidize ethanol and various carbohydrates underlies the production of key food-related metabolites, including acetic acid, gluconic acids, and bacterial cellulose. This review summarizes current knowledge on AAB physiology, metabolic pathways, and ecological adaptations, with emphasis on their relevance to food biotechnology and value-added bioprocesses. AAB plays a central role in traditional and modern food fermentations, contributing to the production of vinegar, cocoa, coffee, kombucha, and other fermented beverages. Their metabolites influence food preservation, sensory attributes, and texture formation, supporting the development of clean-label and sustainable food products. In addition, AAB are increasingly applied in environmental biotechnology, including biodegradation and wastewater treatment, owing to their tolerance to acidic and oxidative stress conditions. Recent advances in metabolic and genetic engineering have enhanced the efficiency, robustness, and product specificity of industrial AAB strains, enabling improved production of organic acids, bacterial cellulose, and other high-value compounds. Emerging evidence also highlights the potential probiotic and postbiotic functions of selected AAB strains, including modulation of gut microbiota, production of bioactive metabolites, and support of intestinal barrier integrity, although these properties remain less explored than in lactic acid bacteria. Despite significant progress, challenges persist in strain standardization, genetic accessibility, and process optimization. Future research should focus on developing advanced engineering tools, improving large-scale fermentation strategies, and further elucidating the functional and health-related properties of AAB. Overall, AAB represents versatile microbial platforms with expanding applications in food science, biotechnology, and sustainable bioprocessing. Full article

The role of gluconeogenesis in kidney disease has increasingly drawn attention. Fructose-1,6-bisphosphatase 1 (FBP1) is a key rate-limiting enzyme in gluconeogenesis that suppresses glycolysis and reduces lactate production. In this study, we first analyzed public transcriptomic datasets of diabetic kidney disease (DKD) and validated the findings in 24-week-old BKS-db mice and in high-glucose-induced human renal tubular epithelial (HK-2) cells. We further constructed tubular-specific FBP1 overexpression/knockdown mouse models via adeno-associated virus serotype 9 (AAV-9) and combined pharmacological inhibition of lactate dehydrogenase B (LDHB) to dissect the underlying mechanism. Analysis of public clinical transcriptomic datasets showed that renal tubular FBP1 expression was positively correlated with estimated glomerular filtration rate (eGFR). In vivo, tubular-specific FBP1 overexpression in BKS-db mice reduced 24-h urinary protein and decreased renal lactate accumulation (p < 0.05) compared with diabetic controls. In vitro, high glucose-induced lactate elevation in HK-2 cells was reversed by FBP1 overexpression, while co-treatment with an LDHB inhibitor abolished this protective effect. Our findings suggest that FBP1 represents a potential experimental therapeutic target associated with alleviation of renal lactic acid accumulation and mitochondrial injury in preclinical DKD models. Full article

We evaluated the effects of different levels of DON (LD 441 and HD 1223 μg DON/kg in diet) on the growth performance, immunity, reproductive hormones, and intestinal health of immature gilts. No significant differences were observed in average daily gain, average daily feed intake, or feed to gain ratio between the LD group and the HD group (p > 0.05). The red blood cell count and hematocrit were higher in the LD group compared with the HD group on d 21 (p < 0.05). The gamma-glutamyl transferase activity in the LD group on d 1, 21, 28, 35, and 42 was higher (p < 0.05) compared with the HD group. The aspartate aminotransferase, total antioxidant capacity, and lactic dehydrogenase levels on d 35 were higher in the LD group than those in the HD group (p < 0.05). On d 35, the levels of interleukin 1β, interleukin-4, interleukin-10, tumor necrosis factor-α, and interferon-γ in LD were higher than those in the HD group (p < 0.05). The levels of immunoglobulin A, immunoglobulin M, immunoglobulin G, and complement 4 on d 35 were higher in the LD group compared with those in the HD group (p < 0.05). The gonadotrophin-releasing hormone, luteotrophic hormone, follicle-stimulating hormone, or estradiol did not differ between LD and HD groups throughout the experiment (p > 0.05). For fecal microbiota, Streptococcus in the HD group was reduced compared with the LD group (p < 0.05). In summary, feeding diets contaminated with 1223 μg DON/kg exerted adverse effects on serum profiles of gilts but did not affect their growth performance or reproductive hormones in the present study. Full article

Lignocellulosic biorefineries are limited by the high cost of cellulolytic enzymes. Consolidated bioprocessing (CBP), which integrates saccharification and fermentation in one step, offers a solution to this challenge. In this study, a cellulase-hyperproducing mutant of Talaromyces pinophilus, Y117, was generated from the parental strain TP117 via sequential ultraviolet irradiation and NTG (N-methyl-N′-nitro-N-nitrosoguanidine) mutagenesis. Enzymatic secretion and lignocellulose degradation capacities were evaluated, focusing on agricultural residues, particularly corncob. Y117’s performance was compared with TP117 and Trichoderma reesei Rut-C30 (TR30) under high-solids fermentation. Furthermore, the lactate dehydrogenase A (ldhA) gene from Rhizopus oryzae was heterologously expressed in Y117 to direct hydrolyzed sugars toward lactic acid (LA). Y117 exhibited significantly enhanced enzymatic secretion, achieving FPase activity of 8.9 IU/mL and a substrate utilization rate of 72.2% at 125 g/L corncob solids. Y117 outperformed TP117 and TR30 in cellulase, xylanase, and CMCase activities, as well as growth under high-solids fermentation conditions. In the LA fermentation process, Y117 produced 14.20 g/L LA, a notable improvement compared to TP117 (5.33 g/L) and TR30 (2.71 g/L). While LA productivity and yield currently remain below bacterial benchmarks, the unique CBP capability of Y117 provides a foundation for further metabolic engineering toward industrial viability. The engineered T. pinophilus Y117 demonstrates promising potential as a CBP platform for efficient straw-to-LA conversion, providing a sustainable approach for third-generation biobased materials production. Full article

This case-control study investigated the association between polymorphisms in the dedicator of cytokinesis 2 (DOCK2) gene and susceptibility to COVID-19 in a Mexican population. Methods: Genotyping of five single-nucleotide polymorphisms (SNPs) in the DOCK2 gene (rs9307 A/G, rs1045176 G/T, rs1045168 C/T, rs2112703 A/C, and rs2287727 A/C) was performed using TaqMan assays in 248 COVID-19 patients and 288 healthy controls. Results: No significant differences were observed in the allelic or genotypic distributions of rs1045176 G/T and rs2287727 A/C between cases and controls. However, under multiple genetic inheritance models (co-dominant, dominant, recessive, heterozygous, and additive), the rs9307 A, rs1045168 C, and rs2112703 A alleles were significantly associated with a reduced risk of COVID-19 (p < 0.05). Furthermore, sub-analyses stratified by genotype in COVID-19 patients revealed that the rs9307 AA, rs1045168 CC, and rs2112703 AA genotypes correlated with altered plasma concentrations of lactic acid dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and ferritin. Conclusions: The DOCK2 SNPs rs9307 A/G, rs1045168 C/T, and rs2112703 A/C are associated with decreased susceptibility to COVID-19 in this population and influence plasma levels of LDH, ALT, AST, and ferritin, suggesting a potential role in disease pathogenesis and severity. Full article

Background: Hypoxic environments significantly impair exercise performance, whilst existing interventions are often limited by adverse effects or insufficient efficacy. Objectives and Methods: This study employed network meta-analysis to screen plant bioactive compounds that effectively enhance exercise performance under hypoxic conditions, with subsequent validation of the efficacy and underlying mechanisms of their combined formulations through animal experiments. Results: Results from hypoxic mouse experiments demonstrated that supplementation with the plant bioactive compound combination significantly improved exercise performance, as evidenced by increased weight-loaded swimming time and limb grip strength. Differential metabolite analysis revealed that the intervention altered key metabolic pathways, including the biosynthesis of unsaturated fatty acids and the metabolism of arginine and proline. Supplementation with the plant bioactive compound combination modulated short-chain fatty acid (SCFA) production by gut microbiota, decreased levels of lactic acid (LA), lactate dehydrogenase (LDH), and creatine kinase (CK), maintained blood glucose levels before and after exercise, and increased muscle and hepatic glycogen reserves. These effects collectively improved exercise endurance and performance in mice under hypoxic conditions. Conclusions: The findings provide novel insights into developing functional interventions to enhance exercise performance in hypoxic environments. Full article

Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide, underscoring the need to better understand cardiovascular physiology. A key aspect involves identifying regulatory molecules that govern metabolic shifts. Forkhead box protein O1 (FoxO1) has emerged as a potential regulator; however, its role and underlying mechanisms remain unclear. This study investigated FoxO1 in metabolic adaptation using Wistar rats divided into age groups (fetal, postnatal day 1, postnatal day 7, adult) and treatment groups (control, hypoxia, FoxO1 inhibitor, combination). Hypoxia (12–14% O₂) and FoxO1 inhibitor (AS1842856, 10 mg/kgBW/day) were administered accordingly. Parameters assessed included hypoxia inducible factor 1 α (HIF-1α), FoxO1 mRNA and protein, glucose transporter type 1 (GLUT1), glucose transporter type 4 (GLUT4), cluster of differentiation 36 (CD36), hexokinase, pyruvate dehydrogenase kinase isoform 4 (PDK4), phosphoenolpyruvate carboxykinase (PEPCK), lactic acid, malonyl-CoA, carnitine palmitoyltransferase 1 (CPT1), citrate synthase, cytochrome c, and adenosine triphosphate (ATP). ATP production increased with age, associated with higher FoxO1 expression and metabolic shifts. Hypoxia in fetal hearts reduced HIF-1α and FoxO1. FoxO1 inhibition elevated glycolytic and oxidative markers. In conclusion, FoxO1 regulates glycolysis and lipid metabolism, offering insights into cardiac adaptation to hypoxia and potential therapeutic strategies. Full article

Pyruvate dehydrogenase complex deficiency (PDCD) is a heterogenous mitochondrial inborn error in carbohydrate oxidation manifesting as congenital lactic acidosis. PDCD presents diagnostic and therapeutic challenges. While no curative treatment exists for PDCD, certain therapeutic modalities may improve prognosis and ameliorate symptom severity. This article examines the effectiveness of treatments for PDCD and presents a case series of three patients with PDCD. A scoping literature review was conducted for treatments of PDCD. Patient data for case reports was extracted retrospectively from electronic medical records from a large tertiary hospital. We reviewed and summarized findings from seven preclinical studies and ten human studies, which showed that dichloroacetate and the ketogenic diet were the most frequently studied treatments. Therapeutic approaches observed select positive outcomes such as reduced lactate levels, improved neuropathological manifestations, and increased longevity. However, most interventions have yet to be rigorously investigated. Early diagnosis of PDCD is integral, as treatment methods may offer improved clinical and biochemical outcomes. Clinical trials of existing and novel treatments are necessary to improve management and further understand the prognostic potential of this metabolic disorder. Full article

Heyndrickxia coagulans is widely used for industrial L-lactic acid production, but carbon catabolite repression (CCR) and its link to fermentative metabolism remain poorly understood. A ccpA deletion mutant (ΔccpA) and a complementation strain (C-ccpA) were constructed to investigated the physiological, enzymatic, and transcriptomic consequences of CcpA loss. Deletion of ccpA completely abolished glucose-mediated CCR, enabling simultaneous glucose–xylose co-utilization, and triggered a marked shift from L-lactic to mixed-acid fermentation, with an 82.5% reduction in lactate titer accompanied by 24.1-fold and 51.6-fold increases in acetate and formate, respectively. Enzyme activity assays showed that L-lactate dehydrogenase activity was reduced by half, whereas acetate kinase activity increased nearly six-fold. Transcriptomic analysis revealed downregulation of ldhL and upregulation of pflB and ackA. Scale-up fermentation in a 5 L bioreactor confirmed that the wild type directed 90.2% of carbon flux to lactate (yield, 0.95 g/g glucose), compared with only 24.5% in the mutant. All phenotypes were fully restored upon complementation. These results demonstrate that CcpA is as an indispensable dual regulator of both CCR and L-lactic fermentation, providing a foundation for rational metabolic engineering of H. coagulans. Full article

Objectives: While several physiological functions of milt peptides have been discovered, the structural characteristics of Theragra chalcogramma milt peptides (TMP) and their anti-fatigue mechanisms remain unclear. Methods: TMP was obtained by hydrolysis via flavor enzyme and alkaline protease, and its structural characteristics were analyzed. A mice model of exercise-induced fatigue was established. The anti-fatigue effect of TMP was evaluated by determining the main biochemical indices in the serum, liver, and skeletal muscle of mice. Additionally, qPCR analysis was conducted to investigate its regulatory effects on relevant energy metabolism pathways. Results: TMP contained 18.2% branched-chain amino acids, with those with molecular weights below 1000 Da accounting for 91.6%. A total of 154 characteristic peptides, such as VPFPR and LPPGR, were identified from TMP, among which 64% of the peptides contained glutamic acid, arginine, or aspartic acid. Molecular docking of potential bioactive peptides to AMP-activated protein kinase (AMPK) revealed binding energies from −9.1 to −5.5 kcal/mol. The exhaustive swimming test showed that oral administration of TMP prolonged the swimming duration. In the fatigue murine model, TMP reduced blood urea nitrogen and blood lactic acid levels while enhancing the content of muscle glycogen. Meanwhile, TMP significantly increased the activity of glutathione peroxidase and superoxide dismutase and reduced the accumulation of malondialdehyde, demonstrating antioxidant properties. Additionally, TMP significantly decreased creatine kinase and lactate dehydrogenase extravasation, thereby protecting muscle tissue, as corroborated by immunohistochemical analyses. Mechanistically, TMP upregulated AMPK and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) expression, promoting mitochondrial biogenesis via the AMPK/PGC-1α pathway. Conclusions: These findings suggest TMP has potential as a dietary supplement for alleviating physical fatigue. Full article

Luteolin (Ltn), a natural flavonoid, effectively inhibits microglial activation in Alzheimer’s disease (AD) with promising therapeutic potential, but its efficacy is severely limited by the blood–brain barrier (BBB). To overcome this obstacle, this study prepared poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs)—designated as TGN/RAP12-RBC-NPs@Ltn—which were coated with red blood cell membranes (RBCm) functionalized with two peptides, TGN (TGNYKALHPHN) and RAP12 (EAKIEKHNHYQK). The results demonstrated that TGN significantly enhanced BBB permeability, while RAP12 enabled effective targeting and delivery of TGN/RAP12-RBC-NPs@Ltn to microglial mitochondria in the brain. In addition, the presence of RBCm significantly inhibited the phagocytosis of NPs by macrophages, exerting a notable role in immune evasion. Meanwhile, the study confirmed that encapsulating Ltn within NPs significantly enhanced cognitive function in APP/PS1 mice, modulated the expression of key mitochondrial metabolic enzymes—pyruvate dehydrogenase (PDH) and its phosphorylated forms (pS232PDH, pS293PDH, pS300PDH)—in microglia, thereby ameliorating mitochondrial dysfunction and effectively regulating the neuroinflammatory environment in the mouse brain, and ultimately contributed to therapeutic efficacy. From this, it could be seen that TGN/RAP12-RBC-NPs@Ltn could significantly enhance the therapeutic effect of Ltn on AD, providing an effective treatment strategy for delaying the progression of AD. Full article

Diabetic ketoacidosis (DKA) remains a life-threatening complication of diabetes mellitus with suboptimal outcomes despite standard management. Emerging evidence suggests that thiamine (vitamin B1) deficiency may play an under-recognized role in DKA pathophysiology and clinical course. This narrative review synthesizes current evidence regarding thiamine deficiency in diabetes and DKA, examining molecular mechanisms, clinical implications, and the rationale for thiamine supplementation as adjunctive therapy. Thiamine deficiency is highly prevalent in diabetes, with plasma concentrations reduced by approximately 75% compared to healthy controls. In DKA specifically, 25–35% of patients present with thiamine deficiency, which often worsens during insulin therapy. The primary mechanism involves hyperglycemia-induced downregulation of renal thiamine transporters (THTR-1 and THTR-2), resulting in 16–24-fold increased renal clearance and massive urinary losses. Thiamine pyrophosphate serves as an essential cofactor for three critical enzymes in glucose metabolism: pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase. Deficiency impairs these pathways, causing pyruvate accumulation with conversion to lactate (resulting in lactic acidosis), compromised TCA cycle function (reducing ATP production by 40–48%), and decreased NADPH generation (increasing oxidative stress). Clinical manifestations include persistent metabolic acidosis despite standard therapy, myocardial dysfunction with elevated cardiac biomarkers, neurological impairment, and prolonged recovery times. Cellular studies demonstrate that thiamine supplementation significantly improves mitochondrial oxygen consumption in DKA patients. The high prevalence of thiamine deficiency in DKA, compelling biochemical rationale, excellent safety profile, and preliminary mechanistic evidence support the urgent need for large-scale randomized controlled trials examining thiamine supplementation to definitively establish efficacy, optimal dosing, and patient selection criteria. Full article

Fermented vegetables host complex microbiomes that drive flavor and functionality. We compared cowpea pod fermentations produced by a Korean kimchi-style method (HG) versus a Sichuan paocai-style method (SC) to isolate technique-driven effects on community structure and functional potential. Cowpea pods were fermented for 10 days in triplicate, profiled by 16S rRNA (V3-V4) amplicon sequencing, analyzed in QIIME2, and functionally inferred with PICRUSt2. SC exhibited higher alpha diversity (Shannon, Chao1, Simpson) than HG (p < 0.05), and beta-diversity (Bray-Curtis dissimilarity) showed clear separation by fermentation style (PERMANOVA p = 0.001), indicating method-dependent community assembly. Both styles were dominated by lactic acid bacteria, chiefly Leuconostoc, Lactobacillus, and Weissella, but their proportions differed: HG retained higher Leuconostoc/Weissella, whereas SC favored Lactobacillus. Predicted functions diverged accordingly: HG was enriched for carbohydrate-metabolism genes (e.g., β-galactosidase; dextransucrase), consistent with rapid sugar fermentation and possible exopolysaccharide formation; SC showed enrichment of amino-acid-related pathways (e.g., acetolactate synthase; glutamate dehydrogenase), heterolactic fermentation, and γ-aminobutyric acid (GABA) biosynthesis, suggesting broader metabolic outputs relevant to flavor development and potential health attributes. Overall, fermentation technique substantially shapes both the microbiome and its predicted repertoire, with HG prioritizing carbohydrate catabolism and SC showing expanded metabolic potential; these insights can inform starter selection and process control for targeted product qualities. Full article

(1) Background: Plantago major and Taraxacum officinale exhibit high tolerance to soil pollution and are recognised as bioindicators of soil quality. The objectives of the study were to investigate (i) the physicochemical and microbiological properties of rhizosphere soil beneath P. major and T. officinale in different land uses, (ii) the accumulation of elements, phenolic and organic acids in soil as well as in the plants, and (iii) the relationships between these parameters. (2) Methods: Samples were collected from three locations: the sediment retention area, the post-mining area, and the recreational area in May and September. (3) Results: Significant seasonal differences were observed in soil parameters, enzymatic activity, microbial abundance, and the contents of elements, organic acids, and phenolic acids between plant species and sampling areas, with changes reaching several hundred per cent. Correlations were found between dehydrogenase and organic matter, S, Al, Co, Cr, Fe, K, Mg, Mn, P; and phosphatases and Al, Co, Cr, Fe, Mg, Ni, and Mn; as well as between total phenolic content and phosphatases; syringic acid and dehydrogenase; and alkaline phosphatase and lactic and citric acids. (4) Conclusions: The results suggest that plant–soil interactions, in relation to land use, influence rhizosphere biochemistry, thereby impacting soil health and supporting ecosystem recovery. Full article

It remains unclear how metabolites produced by vaginal peroxide-producing lactobacilli influence parameters supporting cervical cancer cell survival. The aim of our study was to investigate the functional response of HeLa cells to cell-free metabolites of vaginal lactobacilli producing peroxide under conditions of oxidative stress. HeLa cells were treated with cell-free metabolites of lactobacilli isolated from the vaginal fluid of healthy women. Subsequently, their resistance to oxidative stress (total number of surviving, apoptotic, and necrotic cells), dehydrogenase activity with the MTT assay, and mitochondrial potential were measured. Pretreatment with cell-free lactobacilli metabolites significantly reduced HeLa cell survival under oxidative stress in most cases; dehydrogenase activity and mitochondrial potential changed to a lesser extent. All HeLa cells pretreated with cell-free lactobacillus metabolites that died due to oxidative stress died apoptotic death. These effects of cell-free lactobacilli metabolites are not always determined by lactic acid levels. These data reveal a new mechanism by which vaginal lactobacilli exert local antitumor protection by inducing controlled cell death in transformed cells. Full article