Nanoparticles of nucleotide-free analogue of vitamin B12 formed in protein nanocarriers and their neuroprotective activity in vivo.

Recently, we have described the first supermolecular nanoentities of vitamin B12 derivative, viz. monocyano form of heptabutyl cobyrinate, unique nanoparticles with strong noncovalent intermolecular interactions, emerging optical and catalytic properties. Their nearest analogue, heptamethyl cobyrinate (ACCby), exhibits bioactivity. Here, we demonstrate the first example of the formation of nanoparticles of this nucleotide-free analogue of vitamin B12 in protein nanocarriers and neuroprotective activity in vivo of the own nanoform of the drug. The preparation and characterization of nanocarriers based on bovine serum albumin (BSA) loaded with vitamin B12 (viz. cyano- and aquacobalamins) and ACCby were performed. Nucleotide-free analogue of vitamin B12 is tightly retained by the protein structure and exists in an incorporated state in the form of nanoparticles. The effect of encapsulated drugs on the character and severity of primary generalized seizures in rats induced by the pharmacotoxicant thiosemicarbazide was studied. Cyanocobalamin and ACCby exhibited a neuroprotective effect. The best influence of the encapsulation on the effectiveness of the drugs was achieved in the case of AСCby, whose bioavailability as a neuroprotector did not change upon introduction in BSA particles, i.e., 33 % of surviving animals were observed upon ACCby administration in free form and in encapsulated state. No surviving rats were observed without the administration of drugs. Thus, BSA nanocarriers loaded by nanoparticles of nucleotide-free analogues of vitamin B12, including hydrophobic ones, can be recommended for neuroprotection and targeted delivery.

Vitamin B12 ameliorates gut epithelial injury via modulating the HIF-1 pathway and gut microbiota.

Inflammatory bowel diseases (IBDs) are immune chronic diseases characterized by recurrent episodes, resulting in continuous intestinal barrier damage and intestinal microbiota dysbiosis. Safe strategies aimed at stabilizing and reducing IBDs recurrence have been vigorously pursued. Here, we constructed a recurrent intestinal injury Drosophila model and found that vitamin B12 (VB12), an essential co-factor for organism physiological functions, could effectively protect the intestine and reduce dextran sulfate sodium-induced intestinal barrier disruption. VB12 also alleviated microbial dysbiosis in the Drosophila model and inhibited the growth of gram-negative bacteria. We demonstrated that VB12 could mitigate intestinal damage by activating the hypoxia-inducible factor-1 signaling pathway in injured conditions, which was achieved by regulating the intestinal oxidation. In addition, we also validated the protective effect of VB12 in a murine acute colitis model. In summary, we offer new insights and implications for the potential supportive role of VB12 in the management of recurrent IBDs flare-ups.

Investigating the potential association between micronutrient levels and non-dipper hypertension patterns in the elderly population: A retrospective analysis.

The goal is to provide foundational data that could spearhead more extensive, prospective research into understanding the influences of micronutrient levels on the nocturnal patterns of hypertension, possibly aiding in identifying potential therapeutic strategies to reduce cardiovascular risk in this demographic. The research employed a retrospective design to analyze the micronutrient levels, including ferritin, folic acid, vitamin B12, and vitamin D, in a limited sample size from a single hospital. However, it is worth noting that the study did not scrutinize other potentially relevant micronutrients and biomarkers and lacked information on potential confounding factors such as lifestyle and dietary habits, physical activity levels, and specific details on antihypertensive medications used. The preliminary findings highlight a significant difference in ferritin levels between dipper and non-dipper groups, indicating a potential role in the development of non-dipper hypertension. Surprisingly, no notable difference was observed in vitamin D levels between the groups. The study underscores the increasing prevalence of hypertension and micronutrient deficiencies as age progresses. Despite its limitations, including limited sample size and potential influences from unaccounted variables, the study hints at a potential relationship between micronutrient levels and non-dipper hypertension. It emphasizes the necessity for larger scale, prospective research to delve deeper into the nature of this relationship, potentially fostering new therapeutic approaches in cardiovascular risk management within the elderly population.

Relationships of B12 and Homocysteine with Outcomes in the SURE-PD, SURE-PD3, and STEADY-PDIII Trials.

Background: DATATOP was a study of early Parkinson's disease (PD) conducted in the 1980 s, before mandatory folic acid fortification in the United States. Our analysis of its baseline serum samples revealed a geometric mean vitamin B12 of 369 pg/mL and homocysteine (tHcy) of 9.5µmol/l. We also found that low B12 predicted greater worsening of ambulatory capacity (AC) and elevated tHcy (>15µmol/L) predicted greater declines in cognitive function. Objective: We sought to measure B12 and tHcy in contemporary trial participants with early PD who had not started dopaminergic treatment and to determine whether these analytes were associated with clinical progression. Methods: We measured B12 and tHcy from baseline and end-of-study blood samples from three recent clinical trials. Results: Baseline geometric mean B12 levels for these studies ranged from 484- 618 pg/ml and for tHcy ranged from 7.4- 10µmol/L. Use of B12-containing supplements ranged from 41- 61%, and those taking supplements had higher B12 and lower tHcy. Those who began levodopa, but were not taking B12-supplements, had greater end-of-study tHcy. There was no association of baseline tHcy > 15µmol/L with annualized change in Montreal Cognitive Assessment and no association of baseline B12 tertiles with change in AC. Conclusions: In these longitudinal trials, B12 levels were higher than for DATATOP, due in large part to increased B12-supplement intake, while tHcy levels were similar. Initiation of levodopa was associated with increases of tHcy in those not taking a B12-containing supplement. These smaller studies did not replicate prior findings of low B12 and elevated tHcy with features of progression, possibly due to higher baseline B12.

Evaluation of serum vitamin B12 and D, iron, ferritin, folate, calcium, phosphorus and magnesium levels in children in palliative care clinic: a single-center cross-sectional study.

BACKGROUND: Pediatric palliative care (PPC) patients are at an elevated risk of malnutrition. Nutritional inadequacy can also cause micronutrient deficiencies. These factors can lead to weight loss, stunted growth, and poor quality of life. Despite the prevalence of these issues, limited research exists in the micronutrient status of PPC patients. The purpose of this study was to determine the vitamin B12 and D, iron, ferritin, folate, calcium, phosphorus, and magnesium levels of PPC patients to contribute to a better understanding of their micronutrient needs as well as the appropriate management of diet and treatment approaches. METHODS: This was a single-center observational cross-sectional retrospective study. This study evaluated the levels of vitamin B12, 25-hydroxyvitamin D, iron, ferritin, folate, calcium, phosphorus, and magnesium in PPC patients. The patients were classified according to the Chronic Complex Conditions (CCC) v2 and then compared. RESULTS: A total of 3,144 micronutrient data points were collected from 822 hospitalizations of 364 patients. At least one micronutrient deficiency was identified in 96.9% of the patients. The most prevalent deficiencies were observed for iron, calcium, and phosphate. In addition, 25-hydroxyvitamin D deficiency was observed in one-third of patients. Calcium, magnesium, phosphorus, folate, and 25-hydroxyvitamin D were negatively correlated with age. CONCLUSION: The results of this study indicate that micronutrient deficiencies are highly prevalent in PPC patients. These findings have the potential to contribute to improvements in the nutritional and therapeutic management of patients.

Pernicious anemia is a common cause of cobalamin deficiency-caused megaloblastic anemia in Hainan, China.

BACKGROUND: Pernicious anemia (PA) is believed to be highly prevalent in Western countries but has rarely been reported in China. The study explores whether PA, an autoimmune disease, is an uncommon cause of cobalamin (vitamin B12) deficiency anemia in China. METHODS: Clinical and hematological data were collected from 90 cobalamin deficiency-caused megaloblastic anemia (MA) patients between July 2014 and December 2021. Through anti-intrinsic factor antibody (IFA) and anti-parietal cell antibody (PCA) testing, PA was distinguished from other causes of cobalamin deficiency leading to MA. Meanwhile, 30 healthy controls (HCs) were included to estimate the positive rates of IFA and PCA. RESULTS: Of the 30 HCs, only one tested positive for IFA, and all 30 tested negative for PCA. Among the 90 patients with cobalamin deficiency-caused MA, 76.7% were positive for IFA, and 47.8% were positive for PCA; a total of 76 patients (84.4%) were diagnosed with PA. The mean follow-up time was 41.0 ± 16.3 months. During the follow-up period, no case relapsed among the continuous cobalamin-supply treatment patients, while 24.4% of patients relapsed due to the interruption of maintenance cobalamin-supplement therapy (the median recurrence time was 54.0 ± 17.7 months). CONCLUSIONS: The proportion of PA in cobalamin deficiency-caused MA patients in Hainan province was higher than 80%, which was more common than expected. Therefore, screening for IFA, PCA, endoscopic biopsy, and thyroid-related parameters are recommended for all cobalamin deficiency-caused MA patients. Furthermore, maintenance cobalamin-supplement therapy is important for PA patients.

This research examines pernicious anemia (PA), a type of anemia caused by vitamin B12 deficiency, which has been widely reported in Western countries but is less known in China. The study focuses on determining if PA is also a significant cause of this deficiency in Hainan, China. Researchers gathered data from patients with megaloblastic anemia (a blood disorder) due to lack of vitamin B12, comparing them with healthy individuals to see how common PA is. The findings reveal that a very high percentage of the patients studied have PA, much higher than expected. This suggests that PA is not as rare in this region of China as previously thought. The study also highlights the importance of continuous treatment with vitamin B12 to prevent the recurrence of the anemia. Based on these results, the researchers recommend that all patients with vitamin B12 deficiency should be tested for PA and continuously receive vitamin B12 supplements to maintain their health once diagnosed with PA. This strategic insight is of paramount importance to medical practitioners in China, potentially paving the way for enhanced clinical management protocols for individuals afflicted by this ailment.

[Vitamin B9 and B12 : clinical manifestations, screening and substitution]. / Vitamine B9 et B12 : manifestations cliniques, dépistage et substitution.

Deficiency in vitamins B9 and B12 are common in general practice, due to their high prevalence in the population, especially among elderly patients. This article will present the clinical manifestations of vitamin B9 and B12 deficiencies, which can sometimes be insidious. We will discuss screening strategies, which are based on the presence of compatible symptoms as well as risk factors for deficiency. The choice of administration route for substitution depends both on severity and etiology; but the oral route has demonstrated similar effectiveness compared to intramuscular administration.

Il est courant de rencontrer des déficits en vitamines B9 et B12 en consultation de médecine de premier recours, en raison de leurs prévalences élevées dans la population générale, surtout chez les patients âgés. Cet article présente les manifestations cliniques de carences en vitamines B9 et B12, qui peuvent parfois être insidieuses et discute des stratégies de dépistage, qui se basent sur la présence de symptômes compatibles ainsi que de facteurs de risque de carence. Concernant la substitution, le choix de la voie d'administration se fait selon la sévérité et l'étiologie ; mais la forme orale a démontré une efficacité similaire à l'administration intramusculaire.

Management of Alzheimer's disease and related neurotoxic pathologies: Role of thiamine, pyridoxine and cobalamin.

Alzheimer's disease (AD) remains one of the most debilitating disease and most common neurological disorder in the world at large. However, with many years of multiple research and billions of dollars invested for the purpose of research, not many therapeutic options exist for the management of this disease. As at 2023, the number has only increased to 7, one of which is a combination of two existing therapies. However, research has continued still in the search for a cure. The roles and functions of thiamine, pyridoxine and cobalamin in the proper function of the nervous system has been well researched over time and their role in the management of neurological diseases have been of interest in the last decade. This review describes the roles of the aforementioned chemicals in the management of different models of AD and AD-like pathologies as mono-therapeutic agents and prospective adjuvant for combination therapy.

Association between gastrectomy and the risk of type 2 diabetes in gastric cancer survivors: A nationwide cohort study.

AIM: Postprandial glycemic fluctuations after gastrectomy are seen in patients with gastric cancer but, no studies have investigated the association between gastrectomy and type 2 diabetes mellitus (T2DM) in gastric cancer survivors. This study aimed to elucidate the relationship between gastrectomy (total or subtotal) and incident T2DM. In addition, we explored whether vitamin B12 supplementation modulates this risk among patients who have undergone total gastrectomy. METHODS: In this large nationwide population-based retrospective cohort study using the National Health Insurance Service database of South Korea, we identified patients aged >20 years who underwent gastrectomy from 2008 to 2015 (n = 150,074) and age- and sex-matched controls without gastrectomy (n = 301,508). A Cox proportional hazards model was used. RESULTS: During the median follow-up duration of 4.4 years after the 2-year time lag after gastrectomy, of the 78,006 subjects, 4,597 (5.9 %) developed T2DM. Compared with matched controls, the adjusted hazard ratio (AHR[95 % confidence interval]) for T2DM of patients with total gastrectomy was 1.34[1.23;1.47]. The corresponding AHR after subtotal gastrectomy was 0.81[0.76;0.86]. Among the patients with total gastrectomy, the risk of T2DM was significantly increased in those who did not receive any vitamin B12 supplementation (AHR=1.60[1.33;1.92]), whereas the risk of T2DM was lower (close to being statistically significant) in those who received continuous vitamin B12 supplementation after gastrectomy (AHR=0.70[0.49;1.01]). CONCLUSION: These results show a significantly reduced risk of T2DM in gastric cancer patients undergoing subtotal gastrectomy and a significantly increased risk of T2DM in gastric cancer patients undergoing total gastrectomy, which is mitigated by continuous vitamin B12 supplementation.

Low concentration of serum vitamin B12 may be a strong predictor of large-artery atherosclerosis stroke: A case-control study.

INTRODUCTION: Identifying controllable risk factors for large-artery atherosclerosis (LAA) stroke is crucial due to its significant role as a leading cause of ischemic stroke. We aimed to validate the correlation of serum vitamin B12 with LAA stroke. METHODS: Inpatients with LAA stroke and healthy controls were retrospectively collected for a case-control study from January 2020 to May 2022. Serum vitamin B12 concentration and other blood indicators, demographic, lifestyle factors and comorbidities were investigated. Logistic regression analysis was used to identify the correlation of serum vitamin B12 concentrations with LAA stroke, meanwhile adjusted for confounding factors. RESULTS: Patients with LAA stroke had significantly lower serum vitamin B12 concentrations in comparison to those of controls. In the fully adjusted model, vitamin B12 (per 1 interquartile range increase, odds ratio [OR] = 0.84, 95 % confidence interval [CI]: 0.77-0.91), vitamin B12 < 200 pg/mL (OR=7.70, 95 %CI: 2.19-27.03) and vitamin B12 < 300 pg/mL (OR=4.19, 95 %CI: 1.82-9.66) were independently factors for LAA stroke. Furthermore, the optimal cut-off values for vitamin B12 to predict LAA stroke were 305.25 pg/mL (area under the curve [AUC] = 0.71) when unadjusted and 308.25 pg/mL when adjusted for age and sex (AUC=0.68). Lower vitamin B12 concentrations were significantly associated with male sex, smoking, older age, higher neutrophil count, higher creatinine, lower folate and higher total homocysteine. CONCLUSION: Results indicate that low concentration of serum vitamin B12 may be a strong predictor for the risk of LAA stroke.

Ocoxin Oral Solution Triggers DNA Damage and Cell Death in Ovarian Cancer.

Ovarian cancer is the most fatal of all the reproductive cancers within the female population, mainly due to its late diagnosis that limits surgery and medical treatment. Classically, ovarian cancer therapy has included conventional chemotherapy, and other therapeutic approaches are now being used to treat these patients, but the outcomes of the disease are still poor. Therefore, new strategies are needed to improve life expectancy and life quality of ovarian cancer patients. Considering that, we investigated the effect of the nutritional supplement Ocoxin Oral Solution (OOS) in ovarian cancer models. OOS contains several nutritional supplements, some of them with demonstrated antitumoral action. In vitro studies showed that OOS inhibited the proliferation of several ovarian cancer cell lines, especially of those representative of the endometrioid subtype, in a time- and dose-dependent manner. A fast cell death induction after OOS treatment was observed, and when the molecular mechanisms leading to this effect were investigated, an activation of the DNA damage checkpoint was detected, as shown by activation (phosphorylation) of CHK1 and CHK2 kinases that was followed by the phosphorylation of the target protein histone H2AX. When tested in animal models of ovarian cancer, OOS reduced tumor growth without any observed secondary effects. Moreover, such reduction in tumor proliferation was caused by the induction of DNA damage as corroborated by the in vivo phosphorylation of CHK2 and Histone H2AX. Finally, OOS potentiated the action of carboplatin or olaparib, the standard of care treatments used in ovarian clinics, opening the possibility of including OOS in combination with those standard of care agents in patients with ovarian cancer.

Vitamin B12 Metabolism: A Network of Multi-Protein Mediated Processes.

The water-soluble vitamin, vitamin B12, also known as cobalamin, plays a crucial role in cellular metabolism, particularly in DNA synthesis, methylation, and mitochondrial functionality. Its deficiency can lead to hematological and neurological disorders; however, the manifestation of these clinical outcomes is relatively late. It leads to difficulties in the early diagnosis of vitamin B12 deficiency. A prolonged lack of vitamin B12 may have severe consequences including increased morbidity to neurological and cardiovascular diseases. Beyond inadequate dietary intake, vitamin B12 deficiency might be caused by insufficient bioavailability, blood transport disruptions, or impaired cellular uptake and metabolism. Despite nearly 70 years of knowledge since the isolation and characterization of this vitamin, there are still gaps in understanding its metabolic pathways. Thus, this review aims to compile current knowledge about the crucial proteins necessary to efficiently accumulate and process vitamin B12 in humans, presenting these systems as a multi-protein network. The epidemiological consequences, diagnosis, and treatment of vitamin B12 deficiency are also highlighted. We also discuss clinical warnings of vitamin B12 deficiency based on the ongoing test of specific moonlighting proteins engaged in vitamin B12 metabolic pathways.

Exploring the association of hyperhomocysteinemia with early pregnancy losses: A retrospective case-control study in a tertiary clinic in Türkiye.

A disturbance in the metabolism of homocysteine in both the mother and the fetus has been implicated in several placental vasculopathy-related disorders, including pregnancy loss. This study aimed to provide insights into the potential role of homocysteine, Vitamin B12, and folic acid in early pregnancy losses, with a specific focus on the Turkish population. The results of 93 pregnant women who experienced miscarriage between 5 and 14 gestational weeks and 93 healthy pregnant women at the same gestational weeks were compared. The demographic and pregnancy characteristics of all pregnant women were recorded. Vitamin B12, folic acid, and homocysteine levels were measured in serum samples obtained from the groups at similar gestational weeks. In addition, any associations between these biomarkers and different types of pregnancy loss, such as spontaneous abortion and missed abortion, were evaluated. Vitamin B12 and folic acid serum levels were significantly lower in women with miscarriages (P = .019, P < .001, respectively). Homocysteine levels were higher in the patient group (P < .001). Logistic regression analysis showed that a higher homocysteine level was the only predictive factor of miscarriage (P = .001, odds ratio = 0.596); however, folic acid and Vitamin B12 were not predictive factors. There was no significant difference in homocysteine and micronutrient levels between women with missed abortions and women with spontaneous abortions (P > .05). Our results support the continuing evidence of a link between maternal homocysteine levels and fetal loss. However, in exploring the shared pathways in the underlying mechanisms causing the 2 forms of pregnancy loss, maternal blood analysis showed no relationship.

Diagnostic Signs and Symptoms of Cyanocobalamin Deficiency at Rural Setting in India: Novel Method of Supplementation.

BACKGROUND: Cyanocobalamin or B12 deficiency is common in the Indian population, and responsible for anemia. Various clinical manifestations include central nervous system and cardiovascular manifestations, secondary to a rise in serum homocysteine levels. METHOD AND PATIENTS: In a routine outpatient department at Bawaskar Hospital and Clinical Research Centre, Mahad, patients with suspected clinical signs and symptoms suggestive of cyanocobalamin deficiency were studied in detail regarding their dietary habits, serum hemoglobin, B12, and homocysteine levels. FINDINGS: A total of 1,992 (female 1,009, 50.75%) were clinically examined in detail. Of these, 945 (49.94%), 999 (50.17%), and 48 (2.40%) were strict vegetarians, both vegetarian and nonvegetarian, and strict nonvegetarians, respectively. Common occupations associated with B12 deficiency include 666 (33.4%) housewives, 396 (19.9%) service workers, 316 (15.9%) businesspeople, 180 (9%), and 198 (9.9%) retired and industrial populations, respectively. Clinical manifestations include recurrent scalp hair loss in 268 (13.5%), poor memory in 240 (12%), tingling and numbness in 200 (10%), and generalized weakness in 387 (19.4%) patients. Additionally, 541 (27.15%) patients had pigmentation of the nail bed, knuckles, oral mucosa, and tongue, while 237 (10.81%) suffered from hypertension and ischemic heart disease. During the process of preparation of vegetarian and nonvegetarian food, there is a 30-48% reduction in vitamin content. Supplementation of vitamin by adding table salt to food on a plate at the time of eating improves the vitamin level in the blood. CONCLUSION: In the absence of laboratory investigations in rural settings, clinical signs and symptoms are helpful in detecting B12 deficiency. Directly adding vitamin powder, similar to table salt, to cooked food on the plate improved blood vitamin levels.

Vitamin B12 status and the risk of developing sepsis in patients with bacterial infection: a prospective observational cohort study.

BACKGROUND: Data have shown that vitamin B12 has immunomodulatory effects via different pathways, which could influence the pathophysiology of sepsis. The objective of this study was to investigate whether vitamin B12 levels, assessed by the measurement of holotranscobalamin (HTC), total vitamin B12 (B12), and methylmalonic acid (MMA, which accumulates in case of B12 deficiency), are associated with the development of sepsis in patients with onset of bacterial infection. METHODS: This was a single-center, prospective observational pilot study. Adult patients who presented to the emergency department with bacterial infection confirmed by a positive microbiological culture result were included in the study and followed up for 6 days to assess whether they developed sepsis or not. The primary objective was to compare HTC concentration in patients who developed sepsis to those who did not develop sepsis. Secondary objectives were the evaluation of B12 and MMA concentrations in those two groups. Multiple logistic regression models were used, with presence of sepsis as the outcome variable, and HTC, B12, and MMA concentrations as predictor variables, separately, and adjusted for potential confounders. RESULTS: From 2019 to 2022, 2131 patients were assessed for eligibility, of whom 100 met the inclusion criteria. One patient was excluded from the analysis due to missing data. Of the 99 patients, 29 developed sepsis. There was no evidence for an association between HTC or B12 concentration and the development of sepsis (OR 0.65, 95% CI 0.31-1.29, p = 0.232, OR 0.84, 95% CI 0.44-1.54, p = 0.584, respectively). There was an association between MMA concentration and the development of sepsis, with a positive effect, i.e. with increasing MMA, the odds for sepsis increased (OR 2.36, 95% CI 1.21-4.87, p = 0.014). This association remained significant when adjusted for confounders (OR 2.72, 95% CI 1.23-6.60, p = 0.018). CONCLUSIONS: Our study found an association between elevated MMA concentration and the development of sepsis. We did not find an association between HTC and B12 concentrations and the development of sepsis. Further, larger studies are warranted, as it could lead to interventional trials investigating whether B12 supplementation provides a clinical benefit to patients with infection or sepsis. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov under the identifier NCT04008446 on June 17, 2019.

Emission-based sensing of cobalt (II) and vitamin B12 via a bis-indole derivative.

In this study, a bis-indole compound was synthesized, characterized by 1H NMR, Fourier transform infrared, and mass spectroscopic measurements and used as a selective and efficient probe for the spectrofluorimetric analysis of Co (II). The cobalt-induced quenching in the emission maximum at 567 nm was considered as the analytical signal in calibration studies. When encapsulated in a polymethyl methacrylate (PMMA) matrix, the bis-indole compound exhibited a limit of detection (LOD) of 3.60 × 10-11 M for Co (II). Vitamin B12, which contains a cobalt ion in the center of a corrin ring in its structure, was also successfully quantified using the same probe. The bis-indole compound showed a linear response based on quenching for increasing concentrations of vitamin B12, partially mimicking the contracted tetrapyrrole ring found naturally in the center of vitamin B12. The LOD for vitamin B12 was found to be 76 nm. Promising photophysical properties of the proposed probe, including high molar extinction coefficient, considerable quantum yield (0.46 and 0.64 in tetrahydrofuran and PMMA, respectively), high Stoke's shift and satisfactory photostability, make it a good choice for fluorescence-based Co (II) determination. The ML3-type stoichiometry of the complex between the dye and cobalt was elucidated both by Job's method and by high-resolution mass spectrometry (HR-MS).

Challenging illness scripts: a case of pernicious anaemia and axonal neuropathy.

This case report presents a male in his 30s with pernicious anaemia, initially diagnosed with autoimmune haemolytic anaemia and thrombocytopenia. Despite improvement with treatment, he developed bilateral leg weakness and numbness, ultimately diagnosed as peripheral neuropathy. Further investigations revealed a spectrum of haematological and neurological manifestations associated with B12 deficiency, challenging the typical illness script of pernicious anaemia. This report underscores the importance of recognising variations in clinical presentation and highlights the need for expanded illness scripts to guide accurate diagnosis and management.

Association between Vitamin E, Vitamin B6, and Vitamin B12 with coronary heart disease.

Conflicting evidence still exists regarding Vitamin B12's involvement in coronary heart disease (CHD). There is no precedent for previous studies to include both Vitamin B12, Vitamin B6, as well as Vitamin E in the consideration of CHD associating factors. Our data derived from the National Health and Nutrition Examination Survey (NHANES), which covers the period 2003-2020. 33,640 samples were included in this cross-sectional study. We used an unadjusted covariates and three adjusted covariates. The intake percentage of Vitamins E, B6, and B12 was categorized into continuous and categorical variables using multivariate logistic regression analysis and subgroup logistic regression. To estimate these trends, we applied the percentage categories of Vitamin E, B6, and B12 intake as continuous variables. We recorded Vitamin E, B6, B12, age, race, BMI, gender, household annual income, education level, hypertension status, diabetes status, smoking status, and drinking status for included samples. Multivariate regression analysis revealed that Vitamin E and B6 were negatively associated with CHD and exerted protective effects, while Vitamin B12 had little correlation with CHD. Based on the quartiles of Vitamin E and Vitamin B6 percentage, the strongest protective effect was observed in the third quartile (Q3). Analyses of subgroups showed the effects of Vitamin B6 and Vitamin E on CHD were more noticeable in women, the participant's BMI was in the 25-30 range, and participants who smoked. We identified the possible protective effect of Vitamin E and Vitamin B6 against CHD, especially in female, obese, and smoking populations, whereas income and education were also viewed as influencing factors that could be taken into account.

Vitamin B12 supplementation improved memory impairment following nicotine withdrawal in adolescent male rats: The role of oxidative stress, inflammatory, BDNF, GFAP, and AChE activity.

The present study aimed to assess the potential effect of vitamin B12 (Vit B12) on cognition impairment caused by nicotine (Nic) cessation in adolescent male rats. Adolescent male rats were categorized into two main groups as vehicle (normal saline, intraperitoneally), and Nic group in which received Nic (2 mg/kg) from 21 to 42 days of ages and then the Nic group were divided into three groups as withdrawal (the animals returned to regular diet without treatment), second and third groups received bupropion (20 mg/kg), and Vit B12 at three different doses including 0.5,1, and 1.5 mg/kg by oral gavage as treatments to attenuate Nic withdrawal symptoms. The last group including normal animals received the highest doses of Vit B12 just in the Nic abstinence period to compare the effect of that with vehicle. In MWM, Vit B12and bupropion increased the time spent in the target quadrant that is strongly associated with spatial memory as well as the more time spent with the NORT. Vit B12 and bupropion modulated both oxidant/antioxidant and inflammatory/anti-inflammatory balance, alongside inhibitory effect on AChE, and GFAP. However, BDNF and amyloid-B showed insignificant difference as compared to Vit B12 and bupropion. Considering the present results and similar related studies, Vit B12 can be introduced as a strong anti-oxidant, and anti-inflammatory agent by which probably improved memory impairment caused by Nic addiction accompanied by withdrawal. Further, other mechanisms including activity reduction of AChE, and GFAP should be considered; however, it needs further investigation and larger-scale evidences.