BiochimiePub Date : 2026-01-30DOI: 10.1016/j.biochi.2026.01.014
Sadanand Naik, Sergey N Fedosov, Namita Mahalle, Sharwari Narawade, Ebba Nexo, Christian W Heegaard
{"title":"High oral doses of vitamin B<sub>12</sub> in early pregnancy improve B<sub>12</sub> status of mother and child irrespective of subsequent supplementation a longitudinal study in B<sub>12</sub> insufficient Indian women supplemented with either milk, vitamin pills, or placebo.","authors":"Sadanand Naik, Sergey N Fedosov, Namita Mahalle, Sharwari Narawade, Ebba Nexo, Christian W Heegaard","doi":"10.1016/j.biochi.2026.01.014","DOIUrl":"10.1016/j.biochi.2026.01.014","url":null,"abstract":"<p><p>B<sub>12</sub> deficiency during pregnancy has been associated with shunted growth, neural tube defects, anemia, and neuro-cognitive disorders. The optimal prevention strategy remains to be found. Here we explore the effect of high doses of oral B<sub>12</sub> in early pregnancy followed by physiological doses of B<sub>12</sub> or placebo. The women (B<sub>12</sub> < 146 pmol/l) were recruited before week 17 and divided into three groups, all primed for 14 days with oral B<sub>12</sub> = 5 mg/day. Then onwards, the participants daily received 400 ml of milk (HO-B<sub>12</sub> = 1.6 μg; n = 31), B<sub>12</sub>-pills (CN-B<sub>12</sub> = 1.6 μg; n = 32), or placebo (n = 13) until 4 months postpartum. Blood was drawn at baseline, ½ - 6 months after baseline; on the day of delivery (including cord blood); and at 4-month postpartum (child and mother). B<sub>12</sub> status was assessed by measuring plasma B<sub>12</sub>, holotranscobalamin (holoTC), and homocysteine (Hcy). Birth parameters were recorded. Comparable changes were achieved following high dose administration of both B<sub>12</sub>-forms. Plasma total B<sub>12</sub> and holoTC increased 2-3 and 6-10 times, respectively; while total Hcy decreased ≈2-fold. No clear difference was observed during and after interventions with milk, pills and placebo (including newborns). At the end of the study ⅞ of mothers and ⅔ of babies had adequate B<sub>12</sub> status despite its steady downward drift. Our study demonstrates the benefit of an early-stage supplementation to pregnant women with high oral B<sub>12</sub>. A continuous low dose supplementation adds only minor advantages. The results may impact future strategies of ensuring a sufficient B<sub>12</sub> supply during pregnancy.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiochimiePub Date : 2025-12-06DOI: 10.1016/j.biochi.2025.12.002
Sergey N Fedosov
{"title":"The uptake of ingested vitamin B12 and its total body balance: a mathematical model suggests the optimal supplementation strategy.","authors":"Sergey N Fedosov","doi":"10.1016/j.biochi.2025.12.002","DOIUrl":"10.1016/j.biochi.2025.12.002","url":null,"abstract":"<p><p>Impaired or insufficient uptake of vitamin B<sub>12</sub> causes neurological disorders, anemia, and various diffuse symptoms, all historically called pernicious anemia (PA). Maintenance of adequate B<sub>12</sub> body store (B) is important, but the recommended doses and duration of peroral B<sub>12</sub>-supplementation are usually half-empirical. The current work suggests physiologically realistic algebraic equations to express the changes in B via the daily B<sub>12</sub>-uptake. The data from literature were used to estimate the relevant parameters of the equations. The modeled values of B showed that the daily ingestion of B<sub>12</sub> = 3 × 2.0 μg maintains the steady state value of B = 1316/1858/2683 μg in healthy individuals with low/mean/high types of B<sub>12</sub>-uptake. The \"classical\" PA-patients have a highly decreased intrinsic factor (falling from 30 μg of B<sub>12</sub>-equivalents to below 0.2 μg), giving B = 47/81/123 μg for the low/mean/high B<sub>12</sub>-uptakes and the aforementioned doses. Alignment of B with the combined index of B<sub>12</sub>-status (cB12) in a heterogeneous cohort indicated that B > 1250 μg provides the safe B<sub>12</sub>-status for >84 % of the subjects. The risk of PA is associated with B < 400 μg. Repletion of a low body store from B = 400 μg to ≈1250 μg would require a prolonged supplementation of healthy individuals with B<sub>12</sub>-pills, if they receive 1 × 5 μg/day or 1 × 50 μg/day. These schemes are expected to raise B after the time intervals of (not possible)/2200/780 days or 2330/860/480 days, respectively. Only a pill with high B<sub>12</sub> = 5000 μg/day would raise B to 1250 μg in 24/16/10 days.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiochimiePub Date : 2024-05-15DOI: 10.1016/j.biochi.2024.05.014
Ivan Petushkov, Andrey Feklistov, Andrey Kulbachinskiy
{"title":"Highly specific aptamer trap for extremophilic RNA polymerases.","authors":"Ivan Petushkov, Andrey Feklistov, Andrey Kulbachinskiy","doi":"10.1016/j.biochi.2024.05.014","DOIUrl":"https://doi.org/10.1016/j.biochi.2024.05.014","url":null,"abstract":"<p><p>During transcription initiation, the holoenzyme of bacterial RNA polymerase (RNAP) specifically recognizes promoters using a dedicated σ factor. During transcription elongation, the core enzyme of RNAP interacts with nucleic acids mainly nonspecifically, by stably locking the DNA template and RNA transcript inside the main cleft. Here, we present a synthetic DNA aptamer that is specifically recognized by both core and holoenzyme RNAPs from extremophilic bacteria of the Deinococcus-Thermus lineage. The aptamer binds RNAP with subnanomolar affinities, forming extremely stable complexes even at high ionic strength conditions, blocks RNAP interactions with the DNA template and inhibits RNAP activity during transcription elongation. We propose that the aptamer binds at a conserved site within the downstream DNA-binding cleft of RNAP and traps it in an inactive conformation. The aptamer can potentially be used for structural studies to reveal RNAP conformational states, affinity binding of RNAP and associated factors, and screening of transcriptional inhibitors.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiochimiePub Date : 2023-01-24DOI: 10.1016/j.biochi.2023.01.009
Zoltán Szeltner , Györgyi Ferenc , Tünde Juhász , Zoltán Kupihár , Zoltán Váradi , Dávid Szüts , Lajos Kovács
{"title":"Probing telomeric-like G4 structures with full or partial 2′-deoxy-5-hydroxyuridine substitutions","authors":"Zoltán Szeltner , Györgyi Ferenc , Tünde Juhász , Zoltán Kupihár , Zoltán Váradi , Dávid Szüts , Lajos Kovács","doi":"10.1016/j.biochi.2023.01.009","DOIUrl":"https://doi.org/10.1016/j.biochi.2023.01.009","url":null,"abstract":"<div><p><span><span>Guanine<span> quadruplexes (G4s) are stable four-stranded secondary DNA structures held together by noncanonical G-G base tetrads. We synthesised the </span></span>nucleoside analogue 2′-deoxy-5-hydroxyuridine (H) and inserted its phosphoramidite into telomeric repeat-type model </span>oligonucleotides<span><span><span><span>. Full and partial substitutions were made, replacing all guanines in all the three tetrads of a three-tier G4 structure, or only in the putative upper, central, or lower tetrads. We characterised these modified structures using CD, UV absorbance spectroscopy, native gel studies, and a capture oligo-based G4 disruption kinetic assay. The strand separation activity of BLM helicase on these substituted structures was also investigated. Two of the partially H-substituted constructs adopted G4-like structures, but displayed lower thermal stabilities compared to unsubstituted G4. The construct modified in its central tetrad remained mostly denatured, but the possibility of a special structure for the fully replaced variant remained open. H substitutions did not interfere with the G4-resolving activity of BLM helicase, but its efficiency was highly influenced by construct topology and even more by the G4 ligand PhenDC3. Our results suggest that the H modification can be incorporated into G quadruplexes, but only at certain positions to maintain G4 stability. The destabilizing effect observed for 2′-deoxy-5-hydroxyuridine indicates that the </span>cytosine </span>deamination product 5-hydroxyuracil and its nucleoside counterpart in </span>RNA (5-hydroxyuridine), might also be destabilizing in cellular DNA and RNA quadruplexes. The kinetic assay employed in this study can be generally employed for a fast comparison of the stabilities of various G4s either in their free or ligand-bound states.</span></p></div>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":"214 ","pages":"Pages 33-44"},"PeriodicalIF":0.0,"publicationDate":"2023-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49670757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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