Strategies to combat heat stress in Isa Brown layer hens: Unveiling the roles of vitamin A, vitamin E, vitamin K, vitamin C, selenium, folic acid, and in combination.

Background: Due to their efficient insulation, lack of sweat glands, relatively quick metabolic rate, and heightened sensitivity to heat, the poultry industry faces a serious problem with heat stress. Combining vitamins has been demonstrated to be more effective than implementing a single vitamin in reducing the effects of heat stress. Aim: This study aimed to investigate the efficacy of the multivitamin combination in feed on the growth performance, egg quality, and antioxidant enzymes in laying hens exposed to heat stress. Methods: A total of 28 Isa Brown strains aged 18 weeks were randomly designated into seven groups with four replications, i.e., (C-) normal temperature group, (C+) heat stress group, and the others with the administration of vitamin A and E (AE), vitamin K and C (KC), vitamin C and E (CE), vitamin E and selenium (ESE), and vitamin C and folic acid (CAF). Feed intake, feed efficiency, eggshell thickness, shape index, haugh unit (HU), yolk, and albumen index were evaluated at 22, 23, 24, and 25 weeks. Meanwhile, antioxidant enzymes were quantified at 22 and 25 weeks. Results: As a result, feed intake was reported a significant improvement in the AE and CE groups compared to the C+ group. Meanwhile, the feed efficiency was reported to be efficient in the CE and ESE groups. Based on egg quality evaluation, we reported significant shell thickness in the CE, ESE, and CAF groups compared to the C+; yolk index was reported slightly significant results in the AE and CAF groups; albumen index and HU were reported to increase significantly in the CAF group. Meanwhile, superoxide dismutase (SOD), malondialdehyde (MDA), and GPx activity were ameliorated significantly in the ESE and CAF groups. Conclusion: Combinations of multivitamins can thereby enhance feed intake, feed efficiency, egg quality, and antioxidant activity. The CE, ESE, and CAF groups were found to have made equivalent improvements in the eggshell thickness, shape index, HU, yolk, and albumen index.

Antioxidant Properties of Green Plants with Different Vitamin K Contents.

Vitamin K, as a natural protector of our blood, bones, kidneys, and brain, is essential for human health. It is also considered an effective anti-aging agent with comprehensive biological effects, including antifungal, antibacterial, anti-inflammatory, analgesic, and even antioxidant properties. Of these, the least is known about the antioxidant properties of natural vitamin K. To fill this gap, this study compared the antioxidant properties of extracts obtained from commonly consumed green plants with different vitamin K contents with the activity of vitamin K standard solutions at concentrations corresponding to the vitamin K contents in the extracts. Various measurement methods were used in the research (i.e., DPPH, FRAP, CUPRAC, and the ß-carotene bleaching test). Among the tested methods, the ß-carotene bleaching test is the most sensitive in the assessment of this unusual compound. In light of the data presented, the antioxidant response of vitamin K alone is dose-dependent. However, in extracts, the activity of this compound is modulated by other constituents present in them. As a result, the activity does not always correlate with vitamin K content. The presented data supplement the knowledge about the antioxidant properties with the contribution resulting from the presence of vitamin K in green plant extracts.

The Importance of Vitamin K and the Combination of Vitamins K and D for Calcium Metabolism and Bone Health: A Review.

The aim of the present review is to discuss the roles of vitamin K (phylloquinone or menaquinones) and vitamin K-dependent proteins, and the combined action of the vitamins K and D, for the maintenance of bone health. The most relevant vitamin K-dependent proteins in this respect are osteocalcin and matrix Gla-protein (MGP). When carboxylated, these proteins appear to have the ability to chelate and import calcium from the blood to the bone, thereby reducing the risk of osteoporosis. Carboxylated osteocalcin appears to contribute directly to bone quality and strength. An adequate vitamin K status is required for the carboxylation of MGP and osteocalcin. In addition, vitamin K acts on bone metabolism by other mechanisms, such as menaquinone 4 acting as a ligand for the nuclear steroid and xenobiotic receptor (SXR). In this narrative review, we examine the evidence for increased bone mineralization through the dietary adequacy of vitamin K. Summarizing the evidence for a synergistic effect of vitamin K and vitamin D3, we find that an adequate supply of vitamin K, on top of an optimal vitamin D status, seems to add to the benefit of maintaining bone health. More research related to synergism and the possible mechanisms of vitamins D3 and K interaction in bone health is needed.

Effects of sodium dehydroacetate on broiler chicken bones.

Sodium dehydroacetate (DHA-Na) is a fungicidal preservative widely used in food and animal feed. DHA-Na can induce coagulation disorders in rats and poultry by inhibiting carboxylation of vitamin K-dependent proteins; it can also impair bone development in zebrafish. However, the effects of DHA-Na on broiler chicken bones remain unknown. Here, we assessed whether DHA-Na impairs bone development in broiler chickens. We administered Suji yellow chickens with 200 to 800 mg/kg DHA-Na, 2 mg/kg vitamin K, or both for 2 mo. Bone metabolite-related serum indicators, tissue micromorphology, and relevant protein expression were monitored during the treatment period. We also assessed primary chicken osteoblast activity, differentiation, and bone metabolite-related proteins after treatment with DHA-Na, vitamin K, or both. The results demonstrated that DHA-Na reduced bone index values and serum and bone osteoblast differentiation marker levels but blocked bone vitamin K cycle. DHA-Na also increased serum osteoclast differentiation marker levels, as well as the bone ratio of receptor activator of nuclear factor kappa-Β ligand to osteoprotegerin ratio. Moreover, DHA-Na reduced bone trabecular number, thickness, and area and increased trabecular separation considerably. In general, compared with the control group, the DHA-Na group demonstrated impairments in osteoblast activity and differentiation, as well as in the vitamin K cycle. By contrast, vitamin K supplementation led to considerable attenuation of the DHA-Na-induced decrease in osteogenic marker levels, along with a considerable increase in serum bone absorption marker levels and restoration of DHA-Na-induced bone microstructure damage. Vitamin K also attenuated DHA-Na-induced impairment in osteoclasts. In conclusion, the results indicated that in broiler chickens, DHA-Na supplementation can damage bones by inhibiting osteoblast function and increasing osteoclast activity; this damage can be prevented through vitamin K supplementation.

Modification of Gas6 Protein in the Brain by a Functional Endogenous Tissue Vitamin K Cycle.

The TAM receptor ligand Gas6 is known for regulating inflammatory and immune pathways in various organs including the brain. Gas6 becomes fully functional through the post-translational modification of multiple glutamic acid residues into γ-carboxyglutamic in a vitamin K-dependent manner. However, the significance of this mechanism in the brain is not known. We report here the endogenous expression of multiple components of the vitamin K cycle within the mouse brain at various ages as well as in distinct brain glial cells. The brain expression of all genes was increased in the postnatal ages, mirroring their profiles in the liver. In microglia, the proinflammatory agent lipopolysaccharide caused the downregulation of all key vitamin K cycle genes. A secreted Gas6 protein was detected in the medium of both mouse cerebellar slices and brain glial cell cultures. Furthermore, the endogenous Gas6 γ-carboxylation level was abolished through incubation with the vitamin K antagonist warfarin and could be restored through co-incubation with vitamin K1. Finally, the γ-carboxylation level of the Gas6 protein within the brains of warfarin-treated rats was found to be significantly reduced ex vivo compared to the control brains. In conclusion, we demonstrated for the first time the existence of a functional vitamin K cycle within rodent brains, which regulates the functional modification of endogenous brain Gas6. These results indicate that vitamin K is an important nutrient for the brain. Furthermore, the measurement of vitamin K-dependent Gas6 functionality could be an indicator of homeostatic or disease mechanisms in the brain, such as in neurological disorders where Gas6/TAM signalling is impaired.

Antioxidant Metabolism Pathways in Vitamins, Polyphenols, and Selenium: Parallels and Divergences.

Free radicals (FRs) are unstable molecules that cause reactive stress (RS), an imbalance between reactive oxygen and nitrogen species in the body and its ability to neutralize them. These species are generated by both internal and external factors and can damage cellular lipids, proteins, and DNA. Antioxidants prevent or slow down the oxidation process by interrupting the transfer of electrons between substances and reactive agents. This is particularly important at the cellular level because oxidation reactions lead to the formation of FR and contribute to various diseases. As we age, RS accumulates and leads to organ dysfunction and age-related disorders. Polyphenols; vitamins A, C, and E; and selenoproteins possess antioxidant properties and may have a role in preventing and treating certain human diseases associated with RS. In this review, we explore the current evidence on the potential benefits of dietary supplementation and investigate the intricate connection between SIRT1, a crucial regulator of aging and longevity; the transcription factor NRF2; and polyphenols, vitamins, and selenium. Finally, we discuss the positive effects of antioxidant molecules, such as reducing RS, and their potential in slowing down several diseases.

Genetic diversity of macrolides resistant Staphylococcus aureus clinical isolates and the potential synergistic effect of vitamins, C and K3.

BACKGROUND: Macrolide antibiotics have been extensively used for the treatment of Staphylococcus aureus infections. However, the emergence of macrolide-resistant strains of S. aureus has become a major concern for public health. The molecular mechanisms underlying macrolide resistance in S. aureus are complex and diverse, involving both target site modification and efflux pump systems. In this study, we aim to overcome the molecular diversity of macrolide resistance mechanisms in S. aureus by identifying common molecular targets that could be exploited for the development of novel therapeutics. METHODS: About 300 Staphylococcus aureus different isolates were recovered and purified from 921 clinical specimen including urine (88), blood (156), sputum (264), nasal swabs (168), pus (181) and bone (39) collected from different departments in Tanta University Hospital. Macrolide resistant isolates were detected and tested for Multi Drug Resistant (MDR). Gel electrophoresis was performed after the D test and PCR reaction for erm(A), (B), (C), msr(A), and mph(C) genes. Finally, we tried different combinations of Erythromycin or Azithromycin antibiotics with either vitamin K3 or vitamin C. RESULTS: Macrolide resistance S. aureus isolates exhibited 7 major resistance patterns according to number of resistance markers and each pattern included sub patterns or subgroups. The PCR amplified products of different erm genes; analysis recorded different phenotypes of the Staphylococcus aureus isolates according to their different genotypes. In addition, our new tested combinations of Erythromycin and vitamin C, Erythromycin, and vitamin K3, Azithromycin and vitamin C and Azithromycin and vitamin K3 showed significant antibacterial effect when using every antibiotic alone. Our findings provide new insights into the molecular mechanisms of macrolide resistance in S. aureus and offer potential strategies for the development of novel protocols to overcome this emerging public health threat.

No Detectable Coagulation Activation After Vitamin K (MK-7) Supplementation in Patients on Dialysis With Functional Vitamin K Deficiency: A One-Year Randomized, Placebo-Controlled Study.

OBJECTIVE: Patients on dialysis treatment have poor functional vitamin K status, and this may increase the risk of vascular calcification. Vitamin K supplementation may therefore be relevant in patients on dialysis, but the procoagulant effects have not been studied. We evaluated effects of menaquinone-7 (MK-7) supplementation on biomarkers of coagulation in patients on dialysis. METHODS: Double-blinded, placebo-controlled study in 123 patients on dialysis randomized to 52 weeks of vitamin K (MK-7, 360 µg/daily, n = 61) or placebo (n = 62). Measurements at baseline and after 52 weeks of intervention included thrombin generation (endogenous thrombin potential, peak thrombin concentration, time to peak, and lag time); clot activities of vitamin K-dependent coagulation factors (F) II, VII, IX, and X; prothrombin fragment 1 + 2 (F1+2); and proteins induced by vitamin K absence II (PIVKA-II). Between-group differences (vitamin K vs. placebo) at 52 weeks were determined with an analysis of covariance. Within-group changes in vitamin K and placebo groups were analyzed with a paired t-test. Vascular adverse events and serious adverse events were registered based on hospital records, laboratory data, and participant interviews and compared between groups using Fisher's exact test or Pearson's Chi-Squared test. RESULTS: A between-group difference at 52 weeks was observed for PIVKA-II (P < .001). PIVKA-II decreased significantly from baseline to 52 weeks in the vitamin K group, but not in the placebo group. We observed no between-group differences or within-group changes for biomarkers of coagulation, except for FVII clot activity which was reduced in the placebo group (P = .04), and no between-group differences in adverse events and serious adverse events. CONCLUSION: One year of vitamin K supplementation in patients on dialysis has no detectable effects on biomarkers of coagulation activation, clot activities of vitamin K-dependent coagulation factors, and vascular events or death, indicating no procoagulant effects of this treatment.

Vitamin K: New insights related to senescence and cancer metastasis.

Several clinical trials and experimental studies have recently shown that vitamin K (VK) supplementation benefits the human body. Specifically, VK participates in coagulation and is associated with cellular senescence and cancer. VK has a potential anticancer effect in various cancers, such as pancreatic and prostate cancers. Through anti-inflammatory and antioxidant effects, VK can prevent senescence and inhibit cancer metastasis. Therefore, cancer prognosis can be improved by preventing cellular senescence. In addition, VK can inhibit the proliferation, growth, and differentiation of cancer cells through various mechanisms, including induction of c-myc and c-fos genes, regulation of B-cell lymphoma-2 (Bcl-2) and p21 genes, and angiogenesis inhibition. This review aims to discuss the relationship among VK, cellular senescence, and cancer metastasis and thus may improve comprehension of the specific functions of VK in human health. The potential application of VK as an adjuvant therapy for cancer (or in combination with traditional chemotherapy drugs or other vitamins) has also been highlighted.

Improving Cognitive Function with Nutritional Supplements in Aging: A Comprehensive Narrative Review of Clinical Studies Investigating the Effects of Vitamins, Minerals, Antioxidants, and Other Dietary Supplements.

Cognitive impairment and dementia are burgeoning public health concerns, especially given the increasing longevity of the global population. These conditions not only affect the quality of life of individuals and their families, but also pose significant economic burdens on healthcare systems. In this context, our comprehensive narrative review critically examines the role of nutritional supplements in mitigating cognitive decline. Amidst growing interest in non-pharmacological interventions for cognitive enhancement, this review delves into the efficacy of vitamins, minerals, antioxidants, and other dietary supplements. Through a systematic evaluation of randomized controlled trials, observational studies, and meta-analysis, this review focuses on outcomes such as memory enhancement, attention improvement, executive function support, and neuroprotection. The findings suggest a complex interplay between nutritional supplementation and cognitive health, with some supplements showing promising results and others displaying limited or context-dependent effectiveness. The review highlights the importance of dosage, bioavailability, and individual differences in response to supplementation. Additionally, it addresses safety concerns and potential interactions with conventional treatments. By providing a clear overview of current scientific knowledge, this review aims to guide healthcare professionals and researchers in making informed decisions about the use of nutritional supplements for cognitive health.

Characterization of Gla proteoforms and non-Gla peptides of gamma carboxylated proteins: Application to quantification of prothrombin proteoforms in human plasma.

Gamma (γ) carboxylation is an essential post-translational modification in vitamin K-dependent proteins (VKDPs), involved in maintaining critical biological homeostasis. Alterations in the abundance or activity of these proteins have pharmacological and pathological consequences. Importantly, low levels of fully γ-carboxylated clotting factors increase plasma des-γ-carboxy precursors resulting in little or no biological activity. Therefore, it is important to characterize the levels of γ-carboxylation that reflect the active state of these proteins. The conventional enzyme-linked immunosorbent assay for protein induced by vitamin K absence or antagonist II (PIVKA-II) quantification uses an antibody that is not applicable to distinguish different γ-carboxylation states. Liquid chromatography-mass spectrometry (LC-MS) approaches have been utilized to distinguish different γ-carboxylated proteoforms, however, these attempts were impeded by poor sensitivity due to spontaneous neutral loss of CO2 and simultaneous cleavage of the backbone bond in the collision cell. In this study, we utilized an alkaline mobile phase in combination with polarity switching (positive and negative ionization modes) to simultaneously identify and quantify γ-carboxylated VKDPs. The method was applied to compare Gla proteomics of prothrombin (FII) in 10 µL plasma samples of healthy control and warfarin-treated adults. We also identified surrogate non-Gla peptides for seven other VKDPs to quantify total (active plus inactive) protein levels. The total protein approach (TPA) was used to quantify absolute levels of the VKDPs in human plasma.

PM 2.5 juvenile exposure-induced spermatogenesis dysfunction by triggering testes ferroptosis and antioxidative vitamins intervention in adult male rats.

PM2.5 derived from automobile exhaust can cause reproductive impairment in adult males, but the toxic effects of PM2.5 exposure on reproductive function in juvenile male rats and its relationship with ferroptosis have not been reported. In this paper, 30-day-old juvenile male Sprague-Dawley (SD) rats were divided into four groups (blank control, vitamin control, PM2.5, and PM2.5+Vitamin). The blank control group was fed normally, and the vitamin control group was given intragastric administration of vitamins in addition to normal feeding. PM2.5 was administered via tracheal intubation. When the rats were treated for 4 weeks until reaching the period of sexual maturity. A mating test was performed first, and then their testicular and epididymal tissues were studied. Compared with control rats, juvenile male rats exposed to PM2.5 showed a decreased sperm count and fertility rate, redox imbalance, damaged mitochondria, a metabolic disorder of intracellular iron ions, and a significant rise in ferroptosis during the period of sexual maturity. After antioxidative vitamins intervention, the redox imbalance, metabolic disorder of intracellular iron ions, and ferroptosis were all alleviated, leading to the following conclusions: after being exposed to PM2.5 from automobile exhaust, male juvenile rats during the period of sexual maturity have significantly decreased reproductive function. The reproductive toxicity of PM2.5 is closely related to oxidative stress and ferroptosis. In addition, ferroptosis decreases and reproductive function is recovered to some degree after antioxidative vitamins intervention.

The effect of pharmacological treatment in combination with vitamin K on healing in an experimental rat model of osteoporosis.

OBJECTIVES: This study aims to compare the effects of teriparatide, zoledronic acid, and their combination therapy with vitamin K on osteoporotic rats. MATERIALS AND METHODS: We divided a total of 50 female Sprague-Dawley rats into five groups: A (the control group), B and D (the teriparatide group), and C and E (the zoledronic acid group). Following ovariectomy and subcutaneous heparin administration at a dose of 2 IU/kg for four weeks, osteoporosis was created. Groups A, B, and C were fed with standard feed, while Groups D and E were fed with vitamin K-rich feed. After four weeks of treatment, sacrification was performed. The right and left femurs were separated for histopathological and biomechanical evaluation, respectively. For histopathological evaluation, the femurs were decalcified, and the sections were stained with hematoxylin-eosin and evaluated under a light microscope. Fracture healing was evaluated using the classification system as described previously. For biomechanical evaluation, the 3-point stress test and torsion stress test were applied to 10 femurs from each group. RESULTS: Groups B-E were histopathologically and biomechanically superior to Group A in fracture healing of osteoporotic rats; however, it was not statistically significant (p>0.05). The group that received additional vitamin K was histopathologically and biomechanically superior to the group which was fed with standard feed, although it was not statistically significant (p>0.05). CONCLUSION: Our study results indicated that both teriparatide and zoledronic acid had beneficial effects on osteoporotic fractures with comparable histological and biochemical results. Vitamin K promoted teriparatide and zoledronic acid treatment on osteoporotic fracture healing. Based on these findings, combination therapies may yield the most optimal results in biomechanical and histological examinations.

Effect of Menaquinone-7 Supplementation on Arterial Stiffness in Chronic Hemodialysis Patients: A Multicenter Randomized Controlled Trial.

BACKGROUND: There is a very high prevalence of subclinical vitamin K deficiency in patients requiring hemodialysis (HD), and this problem is associated with vascular calcification and arterial stiffness. Vitamin K2 (MK-7) supplementation can improve vitamin K status in HD patients. However, the benefits of vitamin K supplementation on arterial stiffness have still not been established. The present study was conducted to evaluate the efficacy of menaquinone-7 (MK-7) supplementation on arterial stiffness in chronic HD patients. METHODS: This open-label multicenter randomized clinical trial was conducted in 96 HD patients who had arterial stiffness, defined by high carotid femoral pulse wave velocity (cfPWV ≥ 10 m/s). The patients were randomly assigned to receive oral MK-7 (375 mcg once daily) for 24 weeks (n = 50) or standard care (control group; n = 46). The change in cfPWV was the primary outcome. RESULTS: Baseline parameters were comparable between the two groups. There was no significant difference in the change in cPWV at 24 weeks between the MK-7 group and standard care [-6.0% (-20.2, 2.3) vs. -6.8% (-19.0, 7.3), p = 0.24]. However, we found that MK-7 significantly decreased cPWV in patients with diabetes [-10.0% (-15.9, -0.8) vs. 3.8% (-5.8, 11.6), p = 0.008]. In addition, the MK-7 group had a lower rate of arterial stiffness progression, compared to controls (30.2% vs. 39.5%, p = 0.37), especially in diabetes patients (21.4% vs. 72.7%, p = 0.01). No serious adverse events were observed during the 24 weeks. CONCLUSION: Vitamin K supplements provided a beneficial impact in lowering the rate of arterial stiffness progression in chronic hemodialysis patients with diabetes. Possible benefits on cardiovascular outcomes require further investigation.

The additive effect of vitamin K supplementation and bisphosphonate on fracture risk in post-menopausal osteoporosis: a randomised placebo controlled trial.

This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K1 supplementation led to a modest effect on parameters of hip geometry. PURPOSE: Some clinical studies have suggested that vitamin K prevents bone loss and may improve fracture risk. The aim was to assess whether vitamin K supplementation has an additive effect on bone mineral density (BMD), hip geometry and bone turnover markers (BTMs) in post-menopausal women with osteoporosis (PMO) and sub-optimum vitamin K status receiving bisphosphonate, calcium and/or vitamin D treatment. METHODS: We conducted a trial in 105 women aged 68.7[12.3] years with PMO and serum vitamin K1 ≤ 0.4 µg/L. They were randomised to 3 treatment arms; vitamin K1 (1 mg/day) arm, vitamin K2 arm (MK-4; 45 mg/day) or placebo for 18 months. They were on oral bisphosphonate and calcium and/or vitamin D. We measured BMD by DXA, hip geometry parameters using hip structural analysis (HSA) software and BTMs. Vitamin K1 or MK-4 supplementation was each compared to placebo. Intention to treat (ITT) and per protocol (PP) analyses were performed. RESULTS: Changes in BMD at the total hip, femoral neck and lumbar spine and BTMs; CTX and P1NP did not differ significantly following either K1 or MK-4 supplementation compared to placebo. Following PP analysis and correction for covariates, there were significant differences in some of the HSA parameters at the intertrochanter (IT) and femoral shaft (FS): IT endocortical diameter (ED) (% change placebo:1.5 [4.1], K1 arm: -1.02 [5.07], p = 0.04), FS subperiosteal/outer diameter (OD) (placebo: 1.78 [5.3], K1 arm: 0.46 [2.23] p = 0.04), FS cross sectional area (CSA) (placebo:1.47 [4.09],K1 arm: -1.02[5.07], p = 0.03). CONCLUSION: The addition of vitamin K1 to oral bisphosphonate with calcium and/or vitamin D treatment in PMO has a modest effect on parameters of hip geometry. Further confirmatory studies are needed. TRIAL REGISTRATION: The study was registered at Clinicaltrial.gov:NCT01232647.

Evaluating the in-vivo effects of olive oil, soya bean oil, and vitamins against oxidized ghee toxicity.

The aim of this study was to examine the protective role of various lipids (olive and soya oil) and vitamin (E and C) against the toxicity of thermally oxidized ghee in rabbits. Vanaspati ghee was thermally oxidized on a hot plate at 100°C for ten consecutive hours, and the oxidized ghee was stored in a refrigerator at -20°C until administration. Thirty male rabbits were purchased as experimental animals at a local market and were divided into ten corresponding groups of three based on their body weight. The blood samples of 5 ml were collected on day 0, 7, and 14 of the experiment for the analysis of hematological and biochemical serum parameters. We observed that oxidized ghee significantly elevated ALT level by affecting liver hepatocytes. Furthermore, vitamin E rapidly decreased the ALT levels compared to vitamin C and other oils. The oxidized ghee caused a significant increase in cholesterol compared to the other groups. Vitamin E and C showed the best antioxidant activity and decreased cholesterol levels to normal. Histopathological examinations of the normal rabbits' liver sections revealed no significant histological abnormality. The liver of the rabbits fed with oxidized ghee had an intact lobular architecture but the portal tracts showed inflammation and mild fibrosis, the bile ducts showed proliferation, and the hepatocytes showed feathery degeneration. In the liver sections from the groups fed with oxidized ghee and different doses of olive oil inflammation in portal tracts and large vacuoles in the hepatocytes were observed. The group fed with oxidized ghee and vitamin E had intact lobular architecture with no significant histological abnormality in portal tracts but fatty changes were present in the hepatocytes. These findings support the antioxidant activity of vitamins C and E as they reduced liver infection caused by oxidized ghee. It was concluded that oxidized ghee was highly toxic and not safe for consumption. The present study indicated that soya bean oil and vitamin E were more effective in protecting against the toxicity of thermally oxidized ghee than olive oil and vitamin C.

Vitamin K-dependent carboxylation regulates Ca2+ flux and adaptation to metabolic stress in ß cells.

Vitamin K is a micronutrient necessary for γ-carboxylation of glutamic acids. This post-translational modification occurs in the endoplasmic reticulum (ER) and affects secreted proteins. Recent clinical studies implicate vitamin K in the pathophysiology of diabetes, but the underlying molecular mechanism remains unknown. Here, we show that mouse ß cells lacking γ-carboxylation fail to adapt their insulin secretion in the context of age-related insulin resistance or diet-induced ß cell stress. In human islets, γ-carboxylase expression positively correlates with improved insulin secretion in response to glucose. We identify endoplasmic reticulum Gla protein (ERGP) as a γ-carboxylated ER-resident Ca2+-binding protein expressed in ß cells. Mechanistically, γ-carboxylation of ERGP protects cells against Ca2+ overfilling by diminishing STIM1 and Orai1 interaction and restraining store-operated Ca2+ entry. These results reveal a critical role of vitamin K-dependent carboxylation in regulation of Ca2+ flux in ß cells and in their capacity to adapt to metabolic stress.

Epigenetic effects of folate and related B vitamins on brain health throughout life: Scientific substantiation and translation of the evidence for health improvement strategies.

Suboptimal status of folate and/or interrelated B vitamins (B12 , B6 and riboflavin) can perturb one-carbon metabolism and adversely affect brain development in early life and brain function in later life. Human studies show that maternal folate status during pregnancy is associated with cognitive development in the child, whilst optimal B vitamin status may help to prevent cognitive dysfunction in later life. The biological mechanisms explaining these relationships are not clear but may involve folate-related DNA methylation of epigenetically controlled genes related to brain development and function. A better understanding of the mechanisms linking these B vitamins and the epigenome with brain health at critical stages of the lifecycle is necessary to support evidence-based health improvement strategies. The EpiBrain project, a transnational collaboration involving partners in the United Kingdom, Canada and Spain, is investigating the nutrition-epigenome-brain relationship, particularly focussing on folate-related epigenetic effects in relation to brain health outcomes. We are conducting new epigenetics analysis on bio-banked samples from existing well-characterised cohorts and randomised trials conducted in pregnancy and later life. Dietary, nutrient biomarker and epigenetic data will be linked with brain outcomes in children and older adults. In addition, we will investigate the nutrition-epigenome-brain relationship in B vitamin intervention trial participants using magnetoencephalography, a state-of-the-art neuroimaging modality to assess neuronal functioning. The project outcomes will provide an improved understanding of the role of folate and related B vitamins in brain health, and the epigenetic mechanisms involved. The results are expected to provide scientific substantiation to support nutritional strategies for better brain health across the lifecycle.

Effect of vitamin K supplementation on serum calcification propensity and arterial stiffness in vitamin K-deficient kidney transplant recipients: A double-blind, randomized, placebo-controlled clinical trial.

Vitamin K deficiency is common among kidney transplant recipients (KTRs) and likely contributes to progressive vascular calcification and stiffness. In this single-center, randomized, double-blind, placebo-controlled trial, we aimed to investigate the effects of vitamin K supplementation on the primary end point, serum calcification propensity (calciprotein particle maturation time, T50), and secondary end points arterial stiffness (pulse wave velocity [PWV]) and vitamin K status in 40 vitamin K-deficient KTRs (plasma dephosphorylated uncarboxylated matrix Gla protein [dp-ucMGP] ≥500 pmol/L). Participants (35% female; age, 57 ± 13 years) were randomized 1:1 to vitamin K2 (menaquinone-7, 360 µg/day) or placebo for 12 weeks. Vitamin K supplementation had no effect on calcification propensity (change in T50 vs baseline +2.3 ± 27.4 minutes) compared with placebo (+0.8 ± 34.4 minutes; Pbetween group = .88) but prevented progression of PWV (change vs baseline -0.06 ± 0.26 m/s) compared with placebo (+0.27 ± 0.43 m/s; Pbetween group = .010). Vitamin K supplementation strongly improved vitamin K status (change in dp-ucMGP vs baseline -385 [-631 to -269] pmol/L) compared with placebo (+39 [-188 to +183] pmol/L; Pbetween group < .001), although most patients remained vitamin K-deficient. In conclusion, vitamin K supplementation did not alter serum calcification propensity but prevented progression of arterial stiffness, suggesting that vitamin K has vascular effects independent of calciprotein particles. These results set the stage for longer-term intervention studies with vitamin K supplementation in KTRs. TRIAL REGISTRY: EU Clinical Trials Register (EudraCT Number: 2019-004906-88) and the Dutch Trial Register (NTR number: NL7687).

Sodium dehydroacetate-induced disorder of coagulation function in broiler chickens and the protective effect afforded by vitamin K.

Sodium dehydroacetate (S-DHA) is used widely as a preservative in several products, including poultry feed. The anticoagulation effect of 200 mg/kg S-DHA in rats has been reported to accompany a reduction in hepatic expression of vitamin K epoxide reductase complex 1 (VKORC1). Poultry and mammals have different physiology and coagulation systems, and species differences in VKORC1 expression have been found. The effect of S-DHA on blood clotting of poultry has not been studies deeply. S-DHA was given to yellow-plumage broilers (YBs) as single and multiple administrations. Vitamin K3 (VK3) was injected into YBs 2 wk after S-DHA administration. Then, the prothrombin time (PT), partial activated prothrombin time (APTT), plasma levels of vitamin K (VK), factor IX (FIX), and S-DHA, and hepatic expression of VKORC1 were obtained. Chicken hepatocellular carcinoma (LMH) cells were also exposed to S-DHA, and the cell activity, VK level, and FIX level were measured. S-DHA prolonged the PT or APTT significantly, decreased levels of VK and FIX in blood, and inhibited hepatic expression of VKORC1. The maximum changes were 1.15-fold in the PT, 1.42-fold in the APTT, 0.8-fold in the VK level, 0.7-fold in the FIX level, and 0.35-fold in VKORC1 expression compared with controls. The cell activity, VK level, FIX level, and VKORC1/VKORC1L1 expression of LMH cells were reduced significantly at S-DHA doses of 2.0 to 10.0 mM. Prolongation of the PT/APTT and lower levels of VK/FIX in YBs or the lower cell activity and VK/FIX levels in LMH cells induced by S-DHA therapy were resisted significantly by VK3 treatment. We demonstrated that S-DHA could induce a disorder in coagulation function in YBs or in LMH cells via reduction of VKORC1/VKORC1L1 expression, and that VK could resist this anticoagulation effect.