Search Results (736)

Background: Parkinson’s disease (PD) is characterized by a complex interplay of dopaminergic degeneration, glial activation, and lipid metabolic dysregulation. However, accurately describing how natural product interventions remodel these pathologies across distinct brain regions and cellular microenvironments remains a critical challenge. Methods: We established an integrated multi-omics framework to decode the neuroprotective mechanisms of solanesol (Sol) in an MPTP-induced PD mouse model. We combined single-cell eQTL-based Mendelian randomization (scMR), transcriptomic localization, and virtual knockout analyses to prioritize cell-type-specific regulatory nodes across neuronal, glial, and vascular populations, avoiding the limitations of traditional bulk targeting. In vivo behavioral assays were conducted, alongside orthogonal validation via airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) and gene–metabolite co-enrichment analysis, to map regional metabolic networks and structural spatial reprogramming. Results: Computational prioritization highlighted cell-type-specific regulatory nodes including PRKCB, PRKCE, PDGFRB, and FABP3/5. In vivo, Sol attenuated motor and cognitive deficits and largely restored the highly compartmentalized spatial distributions of striatal dopamine, L-DOPA, and acetylcholine. Crucially, AFADESI-MSI and co-enrichment analysis revealed that Sol specifically reversed MPTP-induced spatial disruptions by rescuing key neuromodulatory metabolites—including cervonoyl ethanolamide, phosphatidylcholine species, taurine, and NADHX—which were tightly coupled to sphingolipid signaling, fatty-acid transport, mitochondrial translation, and cell-adhesion pathways. Conclusions: Sol ameliorates PD-like pathology not through a singular target, but by choreographing a spatially and cellularly compartmentalized restoration of lipid–inflammatory homeostasis. Furthermore, our integrated single-cell and spatial metabolomic blueprint sets a new methodological paradigm for elucidating the precise execution programs of natural neurotherapeutics. Full article

Fishmeal reduction is central to sustainable aquafeed development, but low-fishmeal diets may not reproduce all the nutritional and functional properties of fishmeal after lysine and methionine correction. This PRISMA 2020-based systematic review synthesized peer-reviewed feeding trials evaluating nutritional-balancing strategies beyond these two amino acids in low-fishmeal, fishmeal-free, or high-alternative-protein diets. Alternative protein ingredients were treated as dietary matrices rather than interventions, and studies evaluating ingredient replacement alone were excluded. Twenty-three studies were included. Study-level effect sizes were estimable for 21 studies, providing 24 representative performance-related comparisons. Eight comparisons had 95% confidence intervals excluding zero in favor of the intervention, whereas 16 crossed the null; estimates were not pooled because of substantial heterogeneity in species, diet formulation, intervention, dose, and outcome definition. The evidence covered essential and functional amino acids, taurine and related nitrogenous compounds, palatability enhancers, enzymes, phosphorus and mineral balance, antioxidant support, lipid-associated nutrients, and gut-targeted strategies. Phytase provides the clearest mechanism through which phosphorus utilization can be improved in phytate-rich or phosphorus-limited diets. Taurine responses were generally favorable but imprecise in the four marine finfish species. Protein hydrolysates, fermented ingredients, yeast products, probiotics, hydroxyproline, and other additives produce context-dependent benefits for performance, nutrient utilization, intestinal conditions, immunity, stress resistance, or product quality. Across strategies, efficacy depended mainly on matching the intervention to the nutritional or functional limitation created by the complete diet. Nutritional equivalence should therefore be evaluated via integrated production, mechanism-specific, health, product-quality, environmental, and economic outcomes rather than the fishmeal-replacement percentage alone. Full article

FOXO/DAF-16 is involved in stress resistance and metabolic regulation, but the molecular mechanisms of its interaction with hypoxia remain unclear. This study aimed to evaluate the anti-hypoxic effects of Poecilobdella manillensis bioactive peptide (PMP) and to investigate whether IIS/FOXO acts as a key node in mediating the regulation of oxidative stress and metabolic reprogramming. In the chemical hypoxia model of Caenorhabditis elegans (C. elegans) induced by sodium sulfite, PMP treatment improved the survival status and movement, feeding, and reproductive ability of hypoxic C. elegans, and significantly increased their survival rate. It also reduced reactive oxygen species (ROS) and lipofuscin levels in C. elegans, enhancing their tolerance to oxidative and heat stress. In the terminal normobaric hypoxia mice model, PMP intervention prolonged the survival time of hypoxic mice, alleviated the damage of heart, lung, and brain tissues, and increased superoxide dismutase (SOD) activity and glutathione (GSH) levels, and decreased malondialdehyde (MDA) concentrations and lactate dehydrogenase (LDH) activity in serum and tissues of mice. ¹H-NMR metabolomics analysis showed that PMP treatment reversed hypoxia-induced abnormalities in key metabolites such as glucose, lactic acid, glutamic acid, and taurine. Next, we utilized C. elegans mutants deficient in daf-2, age-1, akt-1, daf-16, and hsp-16.2, and further observed the nuclear translocation of DAF-16 in DAF-16::GFP C. elegans. The results showed PMP induced DAF-16 nuclear translocation and upregulated the expression of downstream SOD-3. Key metabolites representing antioxidant and energy metabolism were measured in the daf-16 mutant C. elegans. The results showed that PMP intervention failed to restore the levels of glucose, lactic acid, glutamic acid, and taurine in the mutant. Finally, 12 peptides containing antioxidant-related bioactive amino acid residues in PMP were screened by UPLC-Q-Exactive-MS and peptide biological activity prediction. Among them, molecular docking showed that KPPGP had a good binding with FOXO1. In conclusion, in C. elegans, PMP activated DAF-16/FOXO by inhibiting the Insulin/insulin-like growth factor-1 signaling (IIS) pathway and regulated redox homeostasis and metabolic reprogramming to resist hypoxia injury, and this protective effect was also observed in mouse models. IIS/FOXO can be used as a key node to regulate oxidative stress and energy metabolism under hypoxic conditions, and the identification of KPPGP provides insights into the screening and study of bioactive peptides in natural products. Full article

Bioactive collagen peptides and collagen hydrolysates are dietary proteins whose degradation products also carry signaling activity. This second part of a two-part narrative review addresses the translational dimensions of their bioactivity, integrating veterinary clinical trials, controlled animal-model studies, and human biomedical data, with evidence strictly stratified by type. The gastrointestinal tract acts not only as the absorption site but as a target organ. In cell culture and rodent models, luminal collagen fragments restore tight-junction integrity, alter the microbiome, and shift the enterohepatic bile acid pool; increased secondary bile acid synthesis is proposed to engage the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5). None of these steps have been demonstrated in veterinary clinical patients. The accompanying GLP-1 and PYY response may reflect direct amino acid stimulation of enteroendocrine cells as much as a bile acid-dependent route, and current data do not separate the two. Veterinary trials show objective kinetic improvement in osteoarthritic dogs and horses. Taurine-responsive dilated cardiomyopathy is a reversible, diet-amenable condition; as the principal bile acid conjugation substrate in carnivores, taurine acts on the same bile acid pool as a mechanistically separate input. Recent data implicate prolyl-hydroxyproline in brown adipogenesis, collagen peptides in hippocampal neurogenesis, and taurine in platelet normalisation. The gut–collagen peptide axis is an evolving model linking dietary collagen to systemic metabolic, endocrine, and immune signaling, with implications for companion-animal, equine, and livestock practice. Full article

To address the high energy demand and product losses associated with separating taurine from sodium sulfate (Na₂SO₄) in the ethylene oxide route to taurine, electrodialytic desalination of a simulated taurine/Na₂SO₄ mother liquor was investigated. The effects of applied voltage, circulation flow rate, and initial feed concentration on the desalination rate, product purity, taurine recovery, current efficiency, specific energy consumption, and membrane productivity were evaluated. Ion-transport behavior was further examined using COMSOL Multiphysics^® 6.3. At 14 V, a circulation flow rate of 200 L/h, and initial taurine and Na₂SO₄ concentrations of 100 and 68 g/L, respectively, the process achieved a taurine purity of 99.8% and a recovery of 98.9%. The specific electrical energy consumption of the electrodialysis unit was 0.56 kWh/kg Na₂SO₄, and the membrane productivity was 0.49 kg Na₂SO₄/(m²·h). One of the key findings of this work is that the low-salt stage plays a dominant role in process economics. This observation led to a simple endpoint-control strategy. The ED operation is stopped when the Na₂SO₄ concentration in the dilute compartment drops to about 2 g/L. This avoids prolonged operation under inefficient conditions and reduces ED energy consumption by 16.5%. Within the binary simulated system and the defined cost boundary, the proposed process provided a higher taurine recovery and a lower estimated separation cost than the conventional crystallization route. These results demonstrate the laboratory-scale feasibility of electrodialysis for desalting simulated taurine mother liquor. Full article

Single studies are often cited to support claims of nutritional soundness or unsoundness regarding vegan or meat-based pet foods when compared to nutritional guidelines from authorities such as the Association of American Feed Control Officials (AAFCO), the European Pet Food Industry Federation (FEDIAF), and the National Research Council (NRC). However, there is little overarching evidence concerning the nutritional soundness of these different pet food types. Such overarching evidence is increasingly important as alternative vegan or meat-based pet food types become more available, such as insect-based, raw meat, and microbial protein-based pet foods. In this systematic review, 54 relevant studies examining the nutritional soundness of vegan, vegetarian, or meat-based dog or cat foods were descriptively analyzed. Only 10 (18.5%) studies found no nutritional deficiencies or excesses across their sampled pet foods relative to AAFCO, FEDIAF, or NRC guidelines. Numerous nutrient deficiencies and excesses were found across all pet food types. Most commonly, these included deficiencies in calcium, phosphorus, and zinc for both dog and cat food, as well as the amino acid taurine exclusively in cat food. The nutrients found to be most commonly in excess were also calcium and phosphorus, and copper—with the latter breaching not only FEDIAF requirements, but also EU legislative limits. Meat-based, insect-based, veterinary prescription, and vegan pet food types each had particularly at-risk nutrients that pet food companies should be aware of. For instance, vegan pet foods often performed well in terms of their fatty acid profile and selenium levels, but some had deficiencies in certain B vitamins. In contrast, some meat-based pet foods were prone to selenium deficiencies. Generally speaking, aside from such specific nutritional flaws, problems were observed across all pet food types. In fact, dog and cat foods (including wet and dry, growth and adult maintenance) of various types commonly failed to fulfil multiple nutritional requirements. To safeguard dog and cat health and welfare, urgent interventions are warranted to improve the nutritional soundness of many pet foods. Full article

Aim: Asprosin, a white adipose tissue-derived glucogenic adipokine, and spexin, a satiety-promoting neuropeptide, are dysregulated in obesity, yet their collective modulation by structured exercise and nutritional supplementation remains poorly characterized. This trial investigated the effects of 12 weeks of combined aerobic–resistance training, with and without taurine supplementation, on plasma asprosin, spexin, and body composition in obese men. Methods: Forty-four obese men (BMI ≥ 30 kg/m²) were allocated in a randomized, placebo-controlled, supplement-blinded design to control plus placebo (CON), taurine supplementation alone (SUP; 3 g/day), exercise plus placebo (EX), or exercise plus taurine (EX + SUP; n = 11 per group). The 12-week protocol combined aerobic training at 60% heart rate reserve (Karvonen formula) with progressive resistance training at 60% of one-repetition maximum, with load re-estimated every four weeks. Plasma asprosin and spexin were quantified by ELISA; body fat percentage (BFP) was assessed by bioelectrical impedance analysis. Two-way repeated-measures ANOVA with Bonferroni post hoc correction and Cohen’s d effect size estimation were applied throughout. Results: Significant Group × Time interactions were detected for all five outcomes (all p < 0.05). EX + SUP generated the greatest reductions in plasma asprosin (Δ = −11.20 ng/mL, p < 0.001), body mass (Δ = −5.50 kg, p = 0.003), BMI (Δ = −1.80 kg/m², p = 0.002), and BFP (Δ = −4.90%, p < 0.001), together with the greatest elevation in plasma spexin (Δ = +0.29 ng/mL, p < 0.001); effect sizes were large across all EX + SUP outcomes (Cohen’s d = 1.17 to ≥1.87). CON showed no significant change in any variable (all p > 0.05). Conclusions: Combined aerobic–resistance training with taurine supplementation produced statistically superior, large-magnitude improvements in adipokine regulation and body composition relative to either modality in isolation, demonstrating greater improvements in the combined intervention group compared with either modality applied independently. Given the per-group sample of n = 11, these findings should be considered preliminary and exploratory; independent replication in larger, adequately powered trials is required before any clinical translation can be considered. Full article

Background: Febrile seizures (FSs) are the most common neurological emergency in early childhood; however, the biological basis of disease heterogeneity remains poorly understood. Although growing evidence suggests that gut–brain axis dysregulation contributes to seizure susceptibility, it remains unclear whether gut microbiota-associated metabolic disturbances are linked to clinical phenotypes, particularly simple FS (SFS) and complex FS (CFS). Methods: An integrated multiomics study was conducted in clinically characterized pediatric cohorts, comprising 50 children with FS and 50 healthy controls, and their gut microbiota was profiled via 16S rRNA sequencing. As some pediatric serum specimens did not meet the minimum volume requirement of the analytical platform, serum amino acid profiling was performed in a subset of samples using an equal-volume pooling strategy. In brief, two individual serum samples from the same study group were combined into one composite sample, yielding 25 pooled samples in the FS group and 25 in the control group. Subsequently, untargeted fecal metabolomics was performed in an expanded cohort of 53 healthy controls, 50 children with SFS, and 42 children with CFS. Additionally, the central metabolic profiles of the CFS and SFS groups were compared using untargeted cerebrospinal fluid metabolomics. Given the variation in sample sizes across omics platforms, each dataset was analyzed within its corresponding eligible subset, and cross-omics integration was interpreted primarily at the pathway and phenotype levels. Results: Children with FS exhibited reduced gut microbial diversity and altered microbial composition, characterized by the enrichment of Streptococcus, Enterococcus, and Escherichia–Shigella, along with the depletion of beneficial taxa, including Faecalibacterium, Lachnoclostridium, and Parasutterella. Functional prediction indicated significant changes in amino acid-related pathways, especially arginine and proline metabolism, amino acid metabolism, and glutathione metabolism. Serum profiling showed elevated levels of phenylalanine, kynurenine, and γ-aminobutyric acid, along with reduced levels of tryptophan, threonine, lysine, glutamine, taurine, citrulline, 3-methylhistidine, α-aminobutyric acid, hydroxyproline, and phosphoethanolamine. Correlation analysis identified Lachnoclostridium and Parasutterella as key taxa associated with neuroactive metabolites. Additionally, fecal metabolomics revealed that both SFS and CFS samples exhibited significant metabolic divergence from the controls, with arginine biosynthesis emerging as a shared altered pathway and L-arginine reduced in both phenotypes. Notably, cerebrospinal fluid metabolomics demonstrated clear metabolic separation between CFS and SFS, signifying phenotype-specific central metabolic signatures. Conclusions: FS is related to gut microbiota dysbiosis, systemic amino acid remodeling, and phenotype-associated metabolic stratification. Arginine metabolism may represent a shared mechanistic hub across FS phenotypes, while central metabolic divergence may contribute to the biological distinction between SFS and CFS. These findings establish a multiomics framework for understanding FS pathogenesis and identifying potential biomarkers and therapeutic targets. Full article

Background/Objectives: Intensified training in adolescent soccer players increases oxidative stress, muscle damage, inflammation, and immune suppression, but direct comparisons of nutritional countermeasures are lacking. This randomised, double-blind, placebo-controlled trial compared the effects of 14-day coenzyme Q10 (CoQ10) versus taurine supplementation on haematological, oxidative, muscle damage, inflammatory, hormonal, and immune biomarkers in under-19 soccer players undergoing three repeated 90 min Soccer Match Simulation (SMS) sessions. Methods: Twenty-four male players (age 17.9 ± 0.7 years) received placebo (n = 8), CoQ10 (300 mg/day, n = 8), or taurine (4 g/day plus 4 g pre-session, n = 8). Blood was collected at baseline (T0), post-first session (T1), post-third session (T2), and 24 h post-third session (T3). Biomarkers included creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), total antioxidant capacity (TAC), interleukins (IL-6, IL-10, TNF-α), cortisol, testosterone, CD4/CD8 ratio, immunoglobulins (IgA, IgG), and plasma volume (Dill–Costill). Data were analysed by two-way repeated-measures ANOVA. Results: CoQ10 was superior in reducing MDA (T2: 0.83 ± 0.02 vs. 1.24 ± 0.03 μmol/L, p < 0.001), LDH (434 ± 9 vs. 684 ± 12 U/L, p < 0.001), and cortisol (20.2 ± 0.6 vs. 30.4 ± 0.8 μg/dL, p < 0.001), and preserved the testosterone:cortisol ratio (24.5 ± 1.1 vs. 13.6 ± 1.0 × 10⁻³, p < 0.001). CoQ10 was more effective than taurine in lowering IL-6 at T2 (3.5 ± 0.2 vs. 3.9 ± 0.2 pg/mL, p = 0.03), whereas taurine was more effective in increasing IL-10 (7.5 ± 0.2 vs. 5.7 ± 0.2 pg/mL, p = 0.005). Both supplements preserved CD4 counts (CoQ10: 790 ± 13, taurine: 795 ± 14 vs. placebo: 680 ± 15 cells/μL, p < 0.01) and the CD4/CD8 ratio, as well as IgA and IgG levels, with no between-supplement differences for immune outcomes (p > 0.05). No adverse events occurred. Conclusions: For adolescent soccer players undergoing intensified training, CoQ10 may be preferred when the goal is reducing oxidative stress, muscle damage, and catabolic load; taurine may be preferred for targeted anti-inflammatory support (IL-10 elevation). Either supplement effectively attenuated changes in circulating immune biomarkers. These preliminary findings provide evidence-based guidance for targeted sports nutrition, pending confirmation in larger trials. Full article

Background: Taurine is a bioactive amino acid that has great potential for wound healing, but it struggles with poor skin penetration and quick clearance. This study aimed to develop taurine-loaded nanoliposomes (Nlp-Tau) to enable sustained local delivery and improve effectiveness. Methods: Nlp-Tau were prepared using thin-film hydration. We characterized them for size, charge, shape, encapsulation efficiency (EE%), loading efficiency (LE%), and in vitro release. Also, its biocompatibility on human foreskin fibroblasts (HFF) with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) has been assessed. In vitro wound healing potential was further evaluated using a scratch assay. Results: Optimized Nlp-Tau showed favorable properties, including an average hydrodynamic diameter of about 282 nm, a polydispersity index of 0.2, a strong negative zeta potential of −31.3 mV, and a spherical shape. However, transmission electron microscopy (TEM) images revealed diameters of about 142 nm and 194 nm for the drug-free and taurine-loaded particles, respectively. Additionally, EE% and LE% were 20% and 2.5%, respectively. In vitro release in PBS (pH 7.4) followed Higuchi kinetics, showing sustained release over 72 h. Nlp-Tau displayed excellent biocompatibility, with HFF viability significantly higher than other groups at concentrations up to 7 mg/mL. Importantly, in the scratch assay, Nlp-Tau treatment resulted in just 6.8% of the wound area remaining after 48 h, which outperformed free taurine at 10.7%. Conclusions: The Nlp-Tau system we developed offers a stable, biocompatible, and effective delivery method for sustained taurine release. It demonstrates greatly improved in vitro wound closure and shows strong potential for future wound care applications. Full article

Sulfur-containing amino acids (SCAA) and their metabolites constitute an integrated metabolic network essential for central nervous system (CNS) function. In mammals, sulfur metabolism links one-carbon metabolism, the methionine cycle and the transsulfuration pathway, thereby connecting nutrient availability with redox regulation, methylation reactions, neurotransmitter synthesis and cellular adaptation to stress. Among these metabolites, methionine, cysteine, glutathione, taurine, homocysteine and hydrogen sulfide play key roles in neuronal physiology, mitochondrial homeostasis, synaptic plasticity and antioxidant defense. Alterations in SCAA metabolism have been increasingly associated with neurological and neurodevelopment disorders, which share common features such as oxidative stress, mitochondrial dysfunction, altered glutamatergic signaling, impaired methylation capacity and neuroinflammation. These pathological mechanisms are also observed following exposure to toxic metals, suggesting the existence of convergent pathways between environmental neurotoxicity and neurological diseases. Several studies showed that chronic exposure to arsenic, mercury, cadmium, lead, and other toxic metals disrupts sulfur amino acid homeostasis by affecting methionine remethylation, transsulfuration activity, glutathione synthesis and reactive sulfur species production. Due to sulfur-containing metabolites possessing antioxidant and metal-binding properties, these pathways are also involved in adaptive detoxification response. However, sustained disruption of sulfur metabolism may compromise neuronal resilience and increase vulnerability to neurological dysfunction. This narrative review integrates current evidence on the physiological roles of SCAA in the CNS, and examines how toxic metals disrupt sulfur metabolic pathways. By combining findings from experimental studies, human data and exploratory transcriptomic analyses, we propose that disruption of SCAA homeostasis represents a mechanistic link between environmental metal exposure and increased vulnerability to neurological disease. Full article

Onion peel extract (OPE) is rich in polyphenolic compounds with antimicrobial potential. Salmonella Enteritidis (SE) infection in young broiler chicks causes morbidity, reduced growth, and contributes to human gastroenteritis through contaminated poultry products. The spleen is a key secondary lymphoid organ coordinating systemic responses to pathogens in chicken. This study evaluated how dietary OPE influences spleen metabolic profiles during SE infection. Day-old Ross 708 male chicks (n = 128) were assigned to four treatments: CON, CON-SE, OPE (6 g/kg), and OPE-SE. Chicks in CON and OPE received sterile broth, whereas CON-SE and OPE-SE received 2.25 × 10⁸ CFU/mL SE at 2 d of age. At 5 and 12 dpi, spleens from six chicks per treatment were collected for untargeted HPLC-MS metabolomics. A total of 857 metabolites were identified and analyzed using MetaboAnalyst 6.0 (p < 0.05; fold change ≥ 2.0; VIP score > 1.0). In CON-SE chicks, energy generating metabolites (6-phosphogluconic acid, methylmalonic acid, propionic acid) increased, while 13,14-dihydro-15-keto-prostaglandin D2 and kynurenic acid decreased. Dietary OPE elevated several dipeptides (L-Val-Gly, L-Leu-Gly, Gly-Gly-Leu, L-Val-L-Met) and reduced ATP linked metabolites (3,6-di-O-methyl-beta-D-glucose and 3-O-beta-D-galactosyl-sn-glycerol). Enrichment analysis showed that SE infection altered valine, leucine, and isoleucine degradation and aromatic amino acid biosynthesis, whereas OPE enriched galactose and biotin metabolism in uninfected chicks, but enriched tryptophan, taurine and hypotaurine metabolism in SE-infected chicks. Overall, dietary OPE optimized response of metabolic pathways associated with immune activation, unlike corresponding pathways in CON-SE birds. Full article

Background/Objectives: Bile acid synthesis disorders (BASDs) represent a distinct category of progressive familiar cholestatic liver disease. A novel targeted mass spectrometry assay was developed for the accurate measurement of the major urinary atypical bile acids and bile alcohols that are biomarkers for HSD3B7, AKR1D1, CYP7B1 and CYP27A1 deficiencies, the four most common BASDs. Methods: Stable-isotope dilution UPLC tandem mass spectrometry was used for the simultaneous quantification of 12 key atypical bile acid biomarkers in urine from patients with BASD. Typical concentration ranges for these metabolites were established from urine samples from patients with biochemically and/or genetically confirmed BASD and compared with non-cholestatic and cholestatic controls. Results: The separation of major 3β-hydroxy-Δ⁵-bile acid sulfates, taurine- and glycine-conjugated 3-oxo-Δ⁴-bile acids, and bile alcohol glucuronides was achieved in a 20 min chromatographic run with intra- and inter-batch imprecisions of <15% for all metabolites. The mean ± SEM urinary concentration of total 3β-sulfated-Δ⁵-cholenoic acids in patients with HSD3B7 deficiency was 704 ± 204 µmol/L (n = 22), approximately 2000-fold higher than in cholestastic patients (n = 168) or non-cholestatic controls (n = 127). Similarly, the concentration of 5β-cholestane-3α,7α,12α,24,25-pentol-glucuronide, the major bile alcohol, in patients with CYP27A1 deficiency was 95 ± 17 µmol/L (n = 12). For CYP7B1 deficiency, two confirmed cases showed elevated levels (average, 7.5 µmol/L) of the glycine conjugate of 3β-sulfooxy-Δ⁵-bile acid. In AKR1D1 deficiency, total 3-oxo-Δ⁴-bile acids in urine were elevated (81 ± 16 µmol/L, n = 48), but concentrations showed overlap with cholestatic and non-cholestatic controls. Conclusions: A novel quantitative tandem mass spectrometry assay is described for the measurement of the major atypical metabolites and biomarkers in urine applicable to the accurate monitoring of treatment responses, and for the first time typical concentration ranges are established for each of these BASDs. Full article

In Southeast Asia (SEA), Bos indicus (zebu) refers to the traditional cattle, whereas Bos taurus (taurine) refers to exotic breeds imported from foreign countries. Notably, a previous study reported that all Thai cattle dating to 3500–1700 years before present (YBP) belonged to the taurine lineage. This suggests that zebu may have been introduced into Thailand at a later date, subsequently replacing the taurine population. In the present study, we analysed 26 cattle remains from nine archaeological sites across Thailand dated to between 3400 and 600 YBP. Taxonomic classification of the specimens was determined using partial D-loop sequences. DNA from four cattle remains obtained from two archaeological sites (Khao Khuram, dated to 1700–1500 YBP, and Sukhothai Historical Park, dated to 850–650 YBP) was successfully amplified and sequenced. Both phylogenetic and haplotype network analyses showed that these remains were grouped in the same haplotype as modern zebu cattle from India, China, and Cambodia. The results suggest that ancient Thai cattle belonged to the zebu lineage and that zebu cattle were introduced into Thailand from India at least 1700 years ago. Furthermore, genetic relationships suggest two potential routes of introduction into Thailand and other SEA countries via overland and maritime routes. Full article

Background: The reversal of liver fibrosis is crucial for improving outcomes in chronic liver disease. The gut–liver axis, mediated by the intestinal microbiota, plays a significant role in this process. However, its dynamic changes and mechanisms during reversal remain unclear. This study aimed to systematically reveal these dynamics and explore the link between gut microbiota and metabolism in a spontaneous reversal model. Methods: Intestinal contents were collected from mouse model groups (fibrosis, 4-week reversal, and 12-week reversal). The use of 16S rRNA gene sequencing was employed to analyze gut microbiota structure, and untargeted metabolomics was used to profile metabolic changes. Differential metabolites and microbial taxa were identified using multivariate statistical analysis, followed by pathway enrichment analysis. Spearman correlation analysis was used to construct metabolite–microbiota association networks across different reversal stages. Results: Metabolomic analysis showed significant alterations in multiple pathways during reversal. Linoleic and α-linolenic acid metabolism had a high impact in later stages. Taurine and biotin metabolism remained active throughout. Branched-chain amino acid degradation was enriched later. Microbiota analysis revealed significant structural shifts via beta-diversity. Bacteroidota decreased while Firmicutes increased in 4 weeks. Butyrate-producing families increased, and Akkermansia was enriched later. Integrated analysis demonstrated significant correlations between specific bacteria and metabolites, indicating a close microbiota–metabolism association during reversal. Conclusions: This integrated multi-omics study delineates the potential dynamic reorganization of the gut microbiota and host metabolism during spontaneous liver fibrosis reversal. These findings provide a theoretical basis for understanding the gut–liver axis mechanism in fibrosis reversal and for developing microbiota-targeted intervention strategies. Full article