Discovery of a novel symbiotic lineage associated with a hematophagous leech from the genus Haementeria.

Similarly to other strict blood feeders, leeches from the Haementeria genus (Hirudinida: Glossiphoniidae) have established a symbiotic association with bacteria harbored intracellularly in esophageal bacteriomes. Previous genome sequence analyses of these endosymbionts revealed co-divergence with their hosts, a strong genome reduction, and a simplified metabolism largely dedicated to the production of B vitamins, which are nutrients lacking from a blood diet. 'Candidatus Providencia siddallii' has been identified as the obligate nutritional endosymbiont of a monophyletic clade of Mexican and South American Haementeria spp. However, the Haementeria genus includes a sister clade of congeners from Central and South America, where the presence or absence of the aforementioned symbiont taxon remains unknown. In this work, we report on a novel bacterial endosymbiont found in a representative from this Haementeria clade. We found that this symbiont lineage has evolved from within the Pluralibacter genus, known mainly from clinical but also environmental strains. Similarly to Ca. Providencia siddallii, the Haementeria-associated Pluralibacter symbiont displays clear signs of genome reduction, accompanied by an A+T-biased sequence composition. Genomic analysis of its metabolic potential revealed a retention of pathways related to B vitamin biosynthesis, supporting its role as a nutritional endosymbiont. Finally, comparative genomics of both Haementeria symbiont lineages suggests that an ancient Providencia symbiont was likely replaced by the novel Pluralibacter one, thus constituting the first reported case of nutritional symbiont replacement in a leech without morphological changes in the bacteriome. IMPORTANCE: Obligate symbiotic associations with a nutritional base have likely evolved more than once in strict blood-feeding leeches. Unlike those symbioses found in hematophagous arthropods, the nature, identity, and evolutionary history of these remains poorly studied. In this work, we further explored obligate nutritional associations between Haementeria leeches and their microbial symbionts, which led to the unexpected discovery of a novel symbiosis with a member of the Pluralibacter genus. When compared to Providencia siddallii, an obligate nutritional symbiont of other Haementeria leeches, this novel bacterial symbiont shows convergent retention of the metabolic pathways involved in B vitamin biosynthesis. Moreover, the genomic characteristics of this Pluralibacter symbiont suggest a more recent association than that of Pr. siddallii and Haementeria. We conclude that the once-thought stable associations between blood-feeding Glossiphoniidae and their symbionts (i.e., one bacteriome structure, one symbiont lineage) can break down, mirroring symbiont turnover observed in various arthropod lineages.

Dosage exploration of combined B-vitamin supplementation in stroke prevention: a meta-analysis and systematic review.

BACKGROUND: The optimal dosage range for B-vitamin supplementation for stroke prevention has not received sufficient attention. OBJECTIVE: Our aim was to determine the optimal dosage range of a combination of folic acid, vitamin B12, and vitamin B6 supplementation in stroke prevention. METHODS: We searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase database for randomized controlled trials published between January 1966 and April 2023, whose participants received B-vitamin supplementation and that reported the number of stroke cases. Relative risk (RR) was used to measure the effect of combined supplementation on risk of stroke using a fixed-effects model. Risk of bias was assessed with the Cochrane risk-of-bias algorithm. RESULTS: The search identified 14 randomized controlled trials of folic acid combined with vitamin B12 and vitamin B6 supplementation for stroke prevention that included 76,664 participants with 2720 stroke cases. In areas without and with partial folic acid fortification, combined B-vitamin supplementation significantly reduced the risk of stroke by 34% [RR: 0.66; 95% confidence interval (CI): 0.50, 0.86] and 11% (RR: 0.89; 95% CI: 0.79, 1.00), respectively. Further analysis showed that a dosage of folic acid ≤0.8 mg/d and vitamin B12 ≤0.4 mg/d was best for stroke prevention (RR: 0.65; 95% CI: 0.48, 0.86) in these areas. In contrast, no benefit of combined supplementation was found in fortified areas (RR: 1.04; 95% CI: 0.94, 1.16). CONCLUSIONS: Our meta-analysis found that the folic acid combined with vitamin B12 and vitamin B6 supplementation strategy significantly reduced the risk of stroke in areas without and with partial folic acid fortification. Combined dosages not exceeding 0.8 mg/d for folic acid and 0.4 mg/d for vitamin B12 supplementation may be more effective for populations within these areas. This trial was registered at PROSPERO asCRD42022355077.

B Vitamins in Legume Ingredients and Their Retention in High Moisture Extrusion.

Legumes have been recognised as healthy and environmentally friendly protein sources. Knowledge about the vitamin B contents in legume ingredients and extrudates is scarce. In this study, we investigated thiamin, riboflavin, niacin, and folate in various faba bean, lupin, and pea ingredients. Further, the retention of B vitamins in high moisture extrusion was studied. Prior to liquid chromatographic determinations of thiamin, riboflavin, niacin, and folate, vitamins were extracted by acid hydrolysis (niacin), enzymatic treatment (folate), or their combination (thiamin and riboflavin). The contents (on a dry matter basis) varied greatly among different ingredients: the thiamin content was 0.2-14.2 µg/g; riboflavin, 0.3-5.9 µg/g; niacin, 8.8-35.5 µg/g, and folate, 45-1453 ng/g. Generally, the highest levels were in flours and protein concentrates, whereas low levels were observed in isolates. The retention of B vitamins was excellent in high moisture extrusion, except for folate in faba bean, where the folate contents were 42-67% lower in the extrudates than in the respective ingredient mixtures. In terms of both vitamin B contents and their retention, extrudates containing substantial amounts of flour or protein concentrate are promising plant-based sources of thiamin, riboflavin, niacin, and folate.

Reproductive-dependent effects of B vitamin deficiency on lifespan and physiology.

B vitamins constitute essential micronutrients in animal organisms, executing crucial roles in numerous biological processes. B vitamin deficiency can result in severe health consequences, including the impairment of reproductive functions and increased susceptibility to age-related diseases. However, the understanding of how reproduction alters the requirements of each individual B vitamins for healthy aging and lifespan remains limited. Here, utilizing Drosophila as a model organism, we revealed the substantial impacts of deficiencies in specific B vitamins on lifespan and diverse physiological functions, with the effects being significantly shaped by reproductive status. Notably, the dietary absence of VB1, VB3, VB5, VB6, or VB7 significantly decreased the lifespan of wild-type females, yet demonstrated relatively little effect on ovoD1 infertile mutant females' lifespan. B vitamin deficiencies also resulted in distinct impacts on the reproduction, starvation tolerance and fat metabolism of wild-type females, though no apparent effects were observed in the infertile mutant females. Moreover, a deficiency in VB1 reshaped the impacts of macronutrient intervention on the physiology and lifespan of fertile females in a reproductive-dependent manner. Overall, our study unravels that the reproductive status of females serves as a critical modulator of the lifespan and physiological alterations elicited by B-vitamin deficiencies.

Evolution of an Alternative Genetic Code in the Providencia Symbiont of the Hematophagous Leech Haementeria acuecueyetzin.

Strict blood-feeding animals are confronted with a strong B-vitamin deficiency. Blood-feeding leeches from the Glossiphoniidae family, similarly to hematophagous insects, have evolved specialized organs called bacteriomes to harbor symbiotic bacteria. Leeches of the Haementeria genus have two pairs of globular bacteriomes attached to the esophagus which house intracellular "Candidatus Providencia siddallii" bacteria. Previous work analyzing a draft genome of the Providencia symbiont of the Mexican leech Haementeria officinalis showed that, in this species, the bacteria hold a reduced genome capable of synthesizing B vitamins. In this work, we aimed to expand our knowledge on the diversity and evolution of Providencia symbionts of Haementeria. For this purpose, we sequenced the symbiont genomes of three selected leech species. We found that all genomes are highly syntenic and have kept a stable genetic repertoire, mirroring ancient insect endosymbionts. Additionally, we found B-vitamin pathways to be conserved among these symbionts, pointing to a conserved symbiotic role. Lastly and most notably, we found that the symbiont of H. acuecueyetzin has evolved an alternative genetic code, affecting a portion of its proteome and showing evidence of a lineage-specific and likely intermediate stage of genetic code reassignment.

B Vitamins as Adjunctive Treatment for Chronic Heart Failure.

INTRODUCTION: Vitamin B deficiency causes cardiac hypertrophy, reduced cardiac contractility, and arrhythmias.The purpose of this study is to perform a network meta-analysis of randomized controlled trials of vitamin B supplements in a group of 150 patients who meet the eligibility criteria.The study also aims to describe the effect of synthetic multivitamins (pyridoxine, folic acid, and cyanocobalamin) on the laboratory findings reflecting the severity of chronic heart failure (cholesterol, glucose, and fibrinogen). METHODS: The experiment involved a group of people (150 individuals) diagnosed with chronic heart failure with reduced left ventricular ejection fraction. The study compared serum levels of B vitamins measured after the therapy and at baseline. The second part of the study focused on the assessment of the laboratory findings reflecting the severity of cardiovascular pathology and indicating an increased risk of vascular catastrophes. RESULTS: Clinical trials among patients diagnosed with chronic heart failure showed that the intake of synthetic forms of pyridoxine, folic acid, and cyanocobalamin slightly increases systolic, diastolic and central venous pressure while decreasing the heart rate and increasing LVEF. Thiamine acts as a vasodilator. It reduces the cardiac afterload and improves heart function. CONCLUSION: The results obtained can be useful in terms of improving the comprehensive treatment strategy for chronic heart failure and further investigation of the effects produced by the intake of B vitamins.

B-vitamin Treatment Modifies the Mortality Risk Associated with Calcium Channel Blockers in Patients with Suspected Stable Angina Pectoris: A Prospective Cohort Study.

BACKGROUND: Calcium channel blockers (CCBs) are used for the treatment of cardiovascular disease (CVD), including angina pectoris, and hypertension; however, the effect on survival remains uncertain. CCBs impair fibrinolysis and have been linked to elevated plasma homocysteine (Hcy), a CVD risk marker. OBJECTIVE: We explored the association between CCB use and mortality in a large prospective cohort of patients with suspected stable angina pectoris (SAP), and potential effect modifications by Hcy-lowering B-vitamin treatment (folic acid, B12, and/or B6) as 61.8% of the patients participated in a randomized placebo-controlled B-vitamin intervention trial. METHODS: Patient baseline continuous characteristics according to CCB treatment were tested by linear regression. Hazard ratios (HRs) for mortality associated with CCB treatment, also according to B-vitamin intervention, were examined using Cox regression analysis. The multivariable model included CVD risk factors, medical histories, and the use of CVD medications. RESULTS: A total of 3991 patients (71.5 % men) were included, of whom 907 were prescribed CCBs at discharge. During 10.3 years of median follow-up, 20.6% died and 8.9% from cardiovascular- and 11.7% from non-cardiovascular causes. Patients treated with CCBs had higher plasma Hcy, fibrinogen levels, and erythrocyte sedimentation rate (all P<0.001). Furthermore, CCB use was positively associated with mortality, also after multivariable adjustments (HRs [95% CIs]: 1.34 [1.15,1.57], 1.35 [1.08,1.70], and 1.33 [1.09,1.64] for total, CVD, and non-CVD death, respectively). Numerically stronger associations were observed among patients not treated with B-vitamins (HR [95% CI]: 1.54 [1.25, 1.88], 1.69 [1.25, 2.30], and 1.41 [1.06, 1.86] for total, CVD deaths, and non-CVD deaths, respectively), whereas no association was seen in patients treated with B-vitamins (HR [95% CI]: 1.15 [0.91, 1.46], 1.09 [0.76, 1.57], and 1.20 [0.88, 1.65]). CONCLUSIONS: In patients with suspected SAP, CCB treatment was associated with increased mortality risk primarily among patients not treated with B-vitamins.

Effectiveness of vitamin-B supplements on cognition in older adults: A meta-analysis.

OBJECTIVES: We aimed to investigate the efficacy of B-vitamin and folic acid supplementation in slowing down cognitive function decline among older adults. METHODS: We searched databases for trials comparing B-vitamin and folate supplementation versus placebo in older adults identified with or without impaired cognition. RESULTS: 23 articles were eligible and included in this meta-analysis. The mean difference (MD) in homocysteine levels was significant between the compared groups (MD:-4.52; 95%CI:-5.41 to 3.63, P < 0.001). However, the difference in the Mini-Mental State Examination (MMSE) was non-significant between the compared groups with or without cognitive impairment (MD:0.19; 95%CI: -0.148 to 0.531, P = 0.27), and (MD:0.04; 95%CI:-0.1 to 0.18, P = 0.59), respectively. The difference in Clinical Dementia Rating-sum of box (CDR-SOB) scores was non-significant (MD:-0.16; 95%CI:-0.49 to 0.18; P = 0.36). CONCLUSIONS: B-vitamin and folate supplementations significantly reduced homocysteine levels. However, it failed to provide significant benefits over placebo in preventing or slowing the decline in cognitive function.

Chemical and nutritional composition of Pamir yak milk from Xinjiang.

Pamir yak milk is considered to be ideal food for local people, but its nutritional profile has not yet been reported. This study investigated the chemical and nutritional composition of Pamir yak milk, and compared the results with reference composition of goat and cow milk. We found that the Pamir yak milk had higher contents of protein (4.30%), fat (4.63), lactose (5.21%) and total solid (14.84%) than that of goat and cow milk. The predominant amino acids were glutamate (20%), proline (10%), lysine (10%) and leucine (10%), of which the essential amino acids accounted for 48% of the total amino acids. Meanwhile, Pamir yak milk was rich in minerals such as Ca, Fe, Zn and Mg and thiamine (B1 ), niacin (B3 ), Pyridoxine (B6 ) and cobalamin (B12 ) were higher than those of cow and goat milk. Also, medium-chain fatty acids (C12-C16) exhibited the highest level. However, The α -linolenic acid (C18:3), eicosapentaenoic acid and docosahexaenoic acid were found in yak milk. All of the above-mentioned differences were demonstrated by the fact that the yak milk quality may be affecting by pasture production, animal species and nutritive value of the herbage. Therefore, Pamir yak milk is a promising alternative food that may contribute to human health.

B-vitamin supplementation on mitigating post-stroke cognition and neuropsychiatric sequelae: A randomized controlled trial.

BACKGROUND AND PURPOSE: A third of stroke patients suffer from post-stroke cognitive decline, depressive symptoms, and anxiety symptoms. B-vitamin supplementation provides a possible safe and affordable treatment to mitigate post-stroke neuropsychiatric sequelae via reducing homocysteine levels. Our study aims to examine the effect of B-vitamin supplementation in the prevention of post-stroke cognitive decline, depressive symptoms, and anxiety symptoms. Our secondary aims were to investigate associations between baseline factors and the three outcomes. METHODS: Patients were recruited as part of a Singaporean substudy of a randomized controlled trial that examined the effect of B-vitamin supplementation on recurrent cardiovascular events. Cognitive decline, depressive symptoms, and anxiety symptoms were assessed with neuropsychological assessments and Hospital Anxiety and Depression Scale 6 monthly. Cox regression analyses were performed to determine treatment efficacy. Logistic regression used to examine factors associated with cognitive decline, depressive symptoms, and anxiety symptoms. RESULTS: A total of 707 were included in the analyses. Survival and hazards ratio analysis showed no treatment effect of B-vitamins on cognitive decline, depressive symptoms, and anxiety symptoms. Cognitive decline was only associated with age. Depressive symptoms were associated with large anterior cerebral infarcts and hyperlipidemia. CONCLUSIONS: Our study showed no benefit of supplementation with B-vitamins for post-stroke cognitive decline, depressive symptoms, or anxiety symptoms. Depressive symptoms were associated with larger anterior cerebral infarcts, which may be reflective of the disability associated with larger infarcts.

Genome analysis of "Candidatus Aschnera chinzeii," the bacterial endosymbiont of the blood-sucking bat fly Penicillidia jenynsii (Insecta: Diptera: Nycteribiidae).

Insect-microbe endosymbiotic associations are omnipresent in nature, wherein the symbiotic microbes often play pivotal biological roles for their host insects. In particular, insects utilizing nutritionally imbalanced food sources are dependent on specific microbial symbionts to compensate for the nutritional deficiency via provisioning of B vitamins in blood-feeding insects, such as tsetse flies, lice, and bedbugs. Bat flies of the family Nycteribiidae (Diptera) are blood-sucking ectoparasites of bats and shown to be associated with co-speciating bacterial endosymbiont "Candidatus Aschnera chinzeii," although functional aspects of the microbial symbiosis have been totally unknown. In this study, we report the first complete genome sequence of Aschnera from the bristled bat fly Penicillidia jenynsii. The Aschnera genome consisted of a 748,020 bp circular chromosome and a 18,747 bp circular plasmid. The chromosome encoded 603 protein coding genes (including 3 pseudogenes), 33 transfer RNAs, and 1 copy of 16S/23S/5S ribosomal RNA operon. The plasmid contained 10 protein coding genes, whose biological function was elusive. The genome size, 0.77 Mbp, was drastically reduced in comparison with 4-6 Mbp genomes of free-living γ-proteobacteria. Accordingly, the Aschnera genome was devoid of many important functional genes, such as synthetic pathway genes for purines, pyrimidines, and essential amino acids. On the other hand, the Aschnera genome retained complete or near-complete synthetic pathway genes for biotin (vitamin B7), tetrahydrofolate (vitamin B9), riboflavin (vitamin B2), and pyridoxal 5'-phosphate (vitamin B6), suggesting that Aschnera provides these vitamins and cofactors that are deficient in the blood meal of the host bat fly. Similar retention patterns of the synthetic pathway genes for vitamins and cofactors were also observed in the endosymbiont genomes of other blood-sucking insects, such as Riesia of human lice, Arsenophonus of louse flies, and Wigglesworthia of tsetse flies, which may be either due to convergent evolution in the blood-sucking host insects or reflecting the genomic architecture of Arsenophonus-allied bacteria.

Vitamin B-6 and riboflavin, their metabolic interaction, and relationship with MTHFR genotype in adults aged 18-102 years.

BACKGROUND: The generation of the active form of vitamin B-6, pyridoxal 5'-phosphate (PLP), in tissues is dependent upon riboflavin as flavin mononucleotide, but whether this interaction is important for maintaining vitamin B-6 status is unclear. OBJECTIVE: To investigate vitamin B-6 and riboflavin status, their metabolic interaction, and relationship with methylenetetrahydrofolate reductase (MTHFR) genotype in adulthood. METHODS: Data from 5612 adults aged 18-102 y were drawn from the Irish National Adult Nutrition Survey (NANS; population-based sample) and the Trinity-Ulster Department of Agriculture (TUDA) and Genovit cohorts (volunteer samples). Plasma PLP and erythrocyte glutathione reductase activation coefficient (EGRac), as a functional indicator of riboflavin, were determined. RESULTS: Older (≥65 y) compared with younger (<65 y) adults had significantly lower PLP concentrations (P < 0.001). A stepwise decrease in plasma PLP was observed across riboflavin categories, from optimal (EGRac ≤1.26), to suboptimal (EGRac: 1.27-1.39), to deficient (EGRac ≥1.40) status, an effect most pronounced in older adults (mean ± SEM: 76.4 ± 0.9 vs 65.0 ± 1.1 vs 55.4 ± 1.2 nmol/L; P < 0.001). In individuals with the variant MTHFR 677TT genotype combined with riboflavin deficiency, compared with non-TT (CC/CT) genotype participants with sufficient riboflavin, we observed PLP concentrations of 52.1 ± 2.9 compared with 76.8 ±0.7 nmol/L (P < 0.001). In participants with available dietary data (i.e., NANS cohort, n = 936), PLP was associated with vitamin B-6 intake (nonstandardized regression coefficient ß: 2.49; 95% CI 1.75, 3.24; P < 0.001), supplement use (ß: 81.72; 95% CI: 66.01, 97.43; P < 0.001), fortified food (ß: 12.49; 95% CI: 2.08, 22.91; P = 0.019), and EGRac (ß: -65.81; 95% CI: -99.08, -32.54; P < 0.001), along with BMI (ß: -1.81; 95% CI: -3.31, -0.30; P = 0.019). CONCLUSIONS: These results are consistent with the known metabolic dependency of PLP on flavin mononucleotide (FMN) and suggest that riboflavin may be the limiting nutrient for maintaining vitamin B-6 status, particularly in individuals with the MTHFR 677TT genotype. Randomized trials are necessary to investigate the PLP response to riboflavin intervention within the dietary range. The TUDA study and the NANS are registered at www.ClinicalTrials.gov as NCT02664584 (27 January 2016) and NCT03374748 (15 December 2017), respectively.Clinical Trial Registry details: Trinity-Ulster-Department of Agriculture (TUDA) study, ClinicalTrials.gov no. NCT02664584 (January 27th 2016); National Adult Nutrition Survey (NANS), ClinicalTrials.gov no. NCT03374748 (December 15th 2017).

Simultaneous quantification of all B vitamins and selected biosynthetic precursors in seawater and bacteria by means of different mass spectrometric approaches.

B vitamins have high microbiological relevance in the marine environment, but their very low concentrations and the chemical heterogeneity of the individual vitamins make their analysis challenging. Mass spectrometric analysis of B vitamins in environmental samples at trace levels has mainly been performed using triple quadrupole mass spectrometers operated in targeted analysis mode. The development of such a method can be laborious and error prone. Additionally, high-resolution mass spectrometers can be used to measure a sample in full scan mode and subsequently search the total ion current chromatogram for extracted ion chromatograms of targeted vitamins. Three different analytical approaches for trace analysis of all B vitamins and some of their biosynthetic precursors were optimized and compared on two different mass spectrometers. A triple quadrupole mass spectrometer in selected reaction monitoring mode, and a high-resolution orbitrap mass spectrometer in parallel reaction monitoring, as well as in full scan mode were employed. Detection limits down to 10 ng/L were achieved with all three techniques. The methods were applied to a marine water sample from the North Sea and to the cell extract of a bacterial culture of Phaeobacter inhibens. Most vitamins and precursors were found in the bacterial cell extract and the seawater sample with all three measuring methods. The results of this study emphasize that, in addition to tandem mass spectrometry, high-resolution full scan mass spectrometry is a promising technique for the simultaneous detection of structurally diverse B vitamins in complex natural samples. This enables highly sensitive measurements without loss of detailed mass spectrometric information, which is inevitable when using a triple quadrupole system in MS/MS mode.

Serum Homocysteine, Vitamin B12, Folate, and Their Association with Mild Cognitive Impairment and Subtypes of Dementia.

BACKGROUND: Although elevated levels of homocysteine (Hcy) are associated with cognitive impairment and dementia, the relevance of Hcy, vitamin B12, and folate levels to subtypes of dementia are still unknown. OBJECTIVE: To investigate the changes of Hcy, vitamin B12, and folate levels in mild cognitive impairment (MCI) and subtypes of dementia including Alzheimer's disease (AD), vascular dementia (VaD), frontotemporal dementia (FTD), and Lewy body dementia (LBD), and their relationships with cognitive function and magnetic resonance imaging (MRI) markers. METHODS: We measured serum levels of Hcy, vitamin B12, and folate in 257 subjects. Each subject underwent cognitive function assessment and brain MRI test. The Fazekas and temporal lobe atrophy (MTA) visual rating scales were used to assess the degree of white matter hyperintensities and MTA, respectively. RESULTS: Serum levels of Hcy was higher and vitamin B12 was lower in AD, VaD, FTD, and LBD groups than cognitively normal controls. No significant differences of folate levels were found among 6 groups. Hcy levels were positively correlated with MTA total score in AD (r = 0.448, p < 0.001). Vitamin B12 levels were positively correlated with MoCA in VaD (r = 0.497), and negatively correlated with MTA total score in AD (r = - 0.325) (ps < 0.05). Hyperhomocysteinemia may increase the risk of AD (OR = 2.744), VaD (OR = 3.600), and FTD (OR = 3.244) in the adjusted model (ps < 0.05). CONCLUSION: Hcy and vitamin B12 levels are associated with MTA in AD. Vitamin B12 levels are associated with general cognition in VaD. Hyperhomocysteinemia is a risk factor for not only AD and VaD but also FTD.

Meta-analysis of apparent ruminal synthesis and postruminal flow of B vitamins in dairy cows.

As milk production has significantly increased over the past decade(s), existing estimates of the B-vitamin needs of the modern dairy cow are currently being reconsidered, as suboptimal B-vitamin supply may affect metabolic efficiency. At the same time, however, "true" (i.e., biologically active forms, excluding nonfunctional analogs) B-vitamin supply also cannot be adequately estimated by dietary intake, as the rumen microbiota has been shown to play a significant role in synthesis and utilization of B vitamins. Given their complex impact on the metabolism of dairy cows, incorporating these key nutrients into the next generation of mathematical models could help to better predict animal production and performance. Therefore, the purpose of this study was to generate hypotheses of regulation in the absence of supplemental B vitamins by creating empirical models, through a meta-analysis, to describe true B-vitamin supply to the cow (postruminal flow, PRF) and apparent ruminal synthesis (ARS). The database used for this meta-analysis consisted of 340 individual cow observations from 15 studies with 16 experiments, where diet and postruminal digesta samples were (post hoc) analyzed for content of B vitamins (B1, B2, B3, B6, B9, B12). Equations of univariate and multivariate linear form were considered. Models describing ARS considered dry matter intake (DMI, kg/d), B-vitamin dietary concentration [mg/kg of dry matter (DM)] and rumen-level variables such as rumen digestible neutral detergent fiber (NDF) and starch (g/kg of DM), total volatile fatty acids (VFA, mM), acetate, propionate, butyrate, and valerate molar proportions (% of VFA), mean pH, and fractional rates of degradation of NDF and starch (%/h). Models describing PRF considered dietary-level driving variables such as DMI, B-vitamin dietary concentration (mg/kg of DM), starch and crude protein (g/kg of DM) and forage NDF (g/kg of DM). Equations developed were required to contain all significant slope parameters and contained no significant collinearity between driving variables. Concordance correlation coefficient was used to evaluate the models on the developmental data set due to data scarcity. Overall, modeling ARS yielded better-performing models compared with modeling PRF, and DMI was included in all prediction equations as a scalar variable. The B-vitamin dietary concentration had a negative effect on the ARS of B1, B2, B3, and B6 but increased the PRF of B2 and B9. The rumen digestible NDF concentration had a negative effect on the ARS of B2, B3, and B6, whereas rumen digestible starch concentration had a negative effect on the ARS of B1 and a positive effect on the ARS of B9. In the best prediction models, the dietary starch increased PRF of B1, B2, and B9 but decreased PRF of B12. The equations developed may be used to better understand the effect of diet and ruminal environment on the true supply of B vitamins to the dairy cow and stimulate the development of better-defined requirements in the future.

Association between MTHFR polymorphism and seizure control in epileptic patients with hyperhomocysteinaemia

Objective: The aim of this study was to investigate possible associations between MTHFR polymorphism and seizure control of epileptic patients with hyperhomocysteinaemia. Methods: A total of 81 epileptic patients with hyperhomocysteinaemia treated with oxcarbazepine monotherapy were enrolled in this study. All patients were offered vitamin B supplementation (2.5 mg/d folate and 1.5 mg/d mecobalamine) for six months. MTHFR C677T and A1298C polymorphisms, serum homocysteine, folate and vitamin B12 levels as well as seizure frequency and score based on the Hamilton depression scale (HAMD) were evaluated at baseline and after six months of follow-up. Results: Spearman correlation analysis showed that the extent of decline of seizure frequency positively correlated with a dynamic change in serum homocysteine concentration between baseline and after six months of follow-up (t=0.241, p=0.015 [Spearman's coefficient]). For the MTHFR C677T polymorphism, compared to the CC genotype, the TT genotype was associated with a significant downtrend of homocysteine (19.69 vs 10.28 mmol/L, p=0.006) and uptrend of folate (6.21 vs 2.49 ng/mL; p=0.004). The decrease in homocysteine (17.94 vs 12.52 mmol/L, p=0.001) and increase of folate (5.08 vs 2.86 ng/mL; p=0.003) were significantly greater in patients with the T allele compared to those with the C allele. Also, the TT genotype (2.33 vs 1.4, p=0.056) and T allele (1.95 vs 1.38, p=0.037) were associated with a greater decrease in seizure frequency compared to the CC genotype or C allele. The A1298C polymorphism alone was not associated with elevated homocysteine or decreased folate levels at baseline, and showed little association with response to vitamin B supplementation in epileptic patients with hyperhomocysteinaemia. However, in patients with combined 677TT/1298AA or 677TT/1298AC polymorphisms, the changes in homocysteine and folate levels and seizure frequency were more obvious. Significance: MTHFR C677T polymorphism was associated with seizure control in epileptic patients with hyperhomocysteinaemia; individuals with the 677TT genotype or T allele demonstrated better seizure control.

The role of mixed B vitamin intakes on cognitive performance: Modeling, genes and miRNAs involved.

OBJECTIVE: To assess the relationships between mixed B vitamin intakes (B1, B2, B3, B6, B9, B12) and cognitive performance, as well as their molecular mechanisms. METHODS: The associations of mixed B vitamin intakes with cognitive function were assessed using multivariate regression models, weighted quantile sum (WQS), quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR). GeneMANIA, Comparative Toxicogenomics Database, MIENTURNET, miRNAsong were employed as the main data-mining methods. RESULTS: Overall effects of the B vitamin intake mixture were significantly associated with global cognition in the WQS, qgcomp, and BKMR models. A mixture of B vitamins (B1, B2, B3, B9) interacted with the five genes (IL1B, BCL2, CASP3, BAX, PTGS2) and was associated with better cognitive function, especially CASP3 and BAX. Physical interactions (77.6%) were observed to be the most important interactions in gene networks. The IL-18 signaling pathway, apoptosis, and Alzheimer's disease were annotated as the key molecular mechanisms involved in mixed B vitamins' improving cognitive function. NFKB1, ATF3, and NR3C1 were the key significant transcription factors associated with cognitive function targeted by a mixture of B vitamins. The strong interaction and expression of hsa-miR-34a-5p, hsa-miR-128-3p, hsa-miR-181a-5p, and hsa-miR-204-5p are involved in mixed B vitamins' better cognitive performance. We also created and evaluated miRNA sponge sequences for these miRNAs, which might be used to alleviate cognitive decline. The cutoff thresholds for B vitamin intake levels that are associated with cognition performance were reported. CONCLUSIONS: Given the increased incidence of dementia across the world, increasing daily mixed B vitamin intake via regular meals may contribute to minimizing dementia risk. Further studies are warranted to identify these links in well-characterized cohorts of diverse populations, either independently or together.

The Controversial Role of HCY and Vitamin B Deficiency in Cardiovascular Diseases.

Plasma homocysteine (HCY) is an established risk factor for cardiovascular disease CVD and stroke. However, more than two decades of intensive research activities has failed to demonstrate that Hcy lowering through B-vitamin supplementation results in a reduction in CVD risk. Therefore, doubts about a causal involvement of hyperhomocysteinemia (HHcy) and B-vitamin deficiencies in atherosclerosis persist. Existing evidence indicates that HHcy increases oxidative stress, causes endoplasmatic reticulum (ER) stress, alters DNA methylation and, thus, modulates the expression of numerous pathogenic and protective genes. Moreover, Hcy can bind directly to proteins, which can change protein function and impact the intracellular redox state. As most mechanistic evidence is derived from experimental studies with rather artificial settings, the relevance of these results in humans remains a matter of debate. Recently, it has also been proposed that HHcy and B-vitamin deficiencies may promote CVD through accelerated telomere shortening and telomere dysfunction. This review provides a critical overview of the existing literature regarding the role of HHcy and B-vitamin deficiencies in CVD. At present, the CVD risk associated with HHcy and B vitamins is not effectively actionable. Therefore, routine screening for HHcy in CVD patients is of limited value. However, B-vitamin depletion is rather common among the elderly, and in such cases existing deficiencies should be corrected. While Hcy-lowering with high doses of B vitamins has no beneficial effects in secondary CVD prevention, the role of Hcy in primary disease prevention is insufficiently studied. Therefore, more intervention and experimental studies are needed to address existing gaps in knowledge.

D-Lactic acid production from agricultural residues by membrane integrated continuous fermentation coupled with B vitamin supplementation.

BACKGROUND: D-Lactic acid played an important role in the establishment of PLA as a substitute for petrochemical plastics. But, so far, the D-lactic acid production was limited in only pilot scale, which was definitely unable to meet the fast growing market demand. To achieve industrial scale D-lactic acid production, the cost-associated problems such as high-cost feedstock, expensive nutrient sources and fermentation technology need to be resolved to establish an economical fermentation process. RESULTS: In the present study, the combined effect of B vitamin supplementation and membrane integrated continuous fermentation on D-lactic acid production from agricultural lignocellulosic biomass by Lactobacillus delbrueckii was investigated. The results indicated the specific addition of vitamins B1, B2, B3 and B5 (VB1, VB2, VB3 and VB5) could reduce the yeast extract (YE) addition from 10 to 3 g/l without obvious influence on fermentation efficiency. By employing cell recycling system in 350 h continuous fermentation with B vitamin supplementation, YE addition was further reduced to 0.5 g/l, which resulted in nutrient source cost reduction of 86%. A maximum D-lactate productivity of 18.56 g/l/h and optical purity of 99.5% were achieved and higher than most recent reports. CONCLUSION: These findings suggested the novel fermentation strategy proposed could effectively reduce the production cost and improve fermentation efficiency, thus exhibiting great potential in promoting industrial scale D-lactic acid production from lignocellulosic biomass.