pyridoxine oxoglurase (PAK / Glutarase)

Spontaneous Coronary Artery Dissection in Pyridoxine-Responsive Classical Homocystinuria: Expanding the Arterial Phenotype.

McCarron Eamon P EP

Pyridoxine-responsive Seizures During Isoniazid Preventive Therapy in a Breastfed Infant.

Özbay Yeşfa Şebnem YŞ, Erol Mavera Uşaklioğlu MU, Aslan Zeynep Selen ZS

Gut microbial and metabolic biomarkers for early-onset colorectal cancer.

Nofinska Balqis Arche BA, Mizutani Sayaka S, Salim Felix F, Sunakawa Hironori H et al.

Early-onset colorectal cancer (EO-CRC) is a growing global health challenge with poorly understood etiology. While gut microbiota and metabolites are implicated in colorectal carcinogenesis, EO-CRC-associated signatures remain poorly characterized. This study presents the first large-scale multi-omics analysis in Japan cohort to characterize gut microbial and metabolic features of EO-CRC, with cross-cohort validation in an independent China cohort. We enrolled 510 participants (EO-CRC n = 120, late-onset CRC [LO-CRC] n = 282, young healthy controls [yHC] n = 59, old healthy controls [oHC] n = 49); after age- and sex-matching, 324 samples were analyzed using metagenomics, metabolomics, and quantitative polymerase chain reaction (qPCR). Fourteen species formed a shared CRC-associated microbiome core enriched in both EO-CRC and LO-CRC relative to age-matched controls, of which seven were reproducible across both Japan and China cohorts. Beyond this core, 34 and 21 species were enriched exclusively in EO-CRC and LO-CRC, respectively. Among EO-CRC-specific virulence findings, the bft gene of enterotoxigenic Bacteroides fragilis, fadA of Fusobacterium nucleatum, and bai operon genes were enriched in EO-CRC, with cross-cohort validation for fadA and bai operon, and stage-specific enrichement of deoxycholic acid at Stage 0 providing preliminary metabolomic support. Targeted clbP qPCR revealed enrichment of colibactin-producing Escherichia coli specifically in EO-CRC against a background of age-increasing carriage. Metabolomic profiling identified kynurenine enrichment and depletion of vitamin B-related metabolites (pyridoxine, riboflavin, and nicotinamide) as EO-CRC-specific findings; LO-CRC showed distinct enrichment of carnitine, succinate, and spermine with relative butyrate depletion. The choline degradation pathway was enriched specifically in EO-CRC based on Enteropathway analysis. Species-based random forest classifiers distinguished EO-CRC from controls (AUPRC = 0.828; SD = 0.013; 95% CI 0.739-0.909) and generalized robustly to an independent cohort (AUPRC = 0.817; 95% CI 0.717-0.894), substantially outperforming functional gene profiles in cross-cohort settings. Within the Japan cohort, adding metabolomics provided modest additional discriminative value. These findings identify a shared CRC microbiome core reproducible across age groups and cohorts, alongside EO-CRC-specific signatures encompassing enrichment of virulence-associated genes (bft, fadA), colibactin-producing E. coli (clbP), secondary bile acid biosynthetic genes (bai operon), and choline degradation capacity, as well as distinct metabolic perturbations including kynurenine enrichment and vitamin B-related metabolite depletion. Species-based classifiers generalize well across age groups and cohorts, with metabolomics providing complementary discriminatory value. All findings represent cross-sectional associations; longitudinal studies are needed to establish temporal ordering and evaluate clinical utility as non-invasive biomarkers for EO-CRC. Video Abstract.

Pyridoxine attenuates Methcathinone-induced cognitive impairment by suppressing ferroptosis via Nrf2/GPX4 pathway.

Xu Chunming C, Zhou Rukui R, Lv Jieping J, Yun Keming K et al.

The precursor of Methcathinone (MeCa) is a cathinone obtained from the plant Catha edulis Forsk. As one of the most prevalent novel psychoactive substances, MeCa has severe neurotoxicology and contributes cognitive dysfunction. Currently, no effective method is available for stopping its progress. Ferroptosis has been proven to contribute to cognitive deficit pathogenesis. Pyridoxine (Pyr) exhibits antioxidative and neuroprotective effects. However, the underlying mechanisms linking Pyr and ferroptosis in MeCa-induced neurotoxicology remain uncertain. The objective of this study is to explore the neuroprotective effects and the potential molecular mechanisms of Pyr against MeCa-induced neurotoxicology in primary hippocampal neurons and male SD rats. In our study, MeCa decreased hippocampal antioxidant capacity, contributed Fe2+ accumulation and mitochondrial dysfunction, induced cognitive impairment and hippocampal neuron injury. Pyr treatment mitigated ferroptosis, alleviated neuronal injury, and attenuated cognitive impairment by activating the Nrf2/GPX4 pathway. Pyr promoted dissociation of Nrf2 and the translocation to the nucleus, and inhibited MeCa-induced Nrf2 ubiquitin degradation. Pyr effectively rescued MeCa-induced cognitive dysfunction by improving neuronal function and synaptic structure, which is related to inhibiting ferroptosis, at least in part, through activating Nrf2/GPX4 axis.