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Journal of Cachexia, Sarcopenia and... Feb 2024Sepsis-associated muscle weakness is common in patients of intensive care units (ICUs), and it is closely associated with poor outcomes. The mechanism of sepsis-induced...
BACKGROUND
Sepsis-associated muscle weakness is common in patients of intensive care units (ICUs), and it is closely associated with poor outcomes. The mechanism of sepsis-induced muscle weakness is unclear. Recent studies have found that gut microbiota and metabolites are involved in the regulation of skeletal muscle mass and metabolism. This study aimed to investigate the effects of gut microbiota and metabolites on sepsis-associated muscle weakness.
METHODS
In a lipopolysaccharide (LPS)-induced inflammation mouse model, mice with different sensitivities to LPS-induced inflammation were considered as donor mice for the faecal microbiota transplantation (FMT) assay, and recipient mice were divided into sensitive (Sen) and resistant (Res) groups. Skeletal muscle mass and function, as well as colonic barrier integrity were tested and gut microbiota and metabolite composition were analysed in both groups of mice. The effect of intestinal differential metabolite vitamin K1 on LPS-triggered muscle damage was investigated, and the underlying mechanism was explored.
RESULTS
Recipients exhibited varying LPS-triggered muscle damage and intestinal barrier disruption. Tibialis anterior (TA) muscle of Sen exhibited upregulated expression levels of MuRF-1 (0.825 ± 0.063 vs. 0.304 ± 0.293, P = 0.0141) and MAFbx (1.055 ± 0.079 vs. 0.456 ± 0.3, P = 0.0092). Colonic tight junction proteins ZO-1 (0.550 ± 0.087 vs. 0.842 ± 0.094, P = 0.0492) and occludin (0.284 ± 0.057 vs. 0.664 ± 0.191, P = 0.0487) were significantly downregulated in the Sen group. Metabolomic analysis showed significantly higher vitamin K1 in the faeces (P = 0.0195) and serum of the Res group (P = 0.0079) than those of the Sen group. After vitamin K1 intervention, muscle atrophy-related protein expression downregulated (P < 0.05). Meanwhile SIRT1 protein expression were upregulated (0.320 ± 0.035 vs. 0.685 ± 0.081, P = 0.0281) and pNF-κB protein expression were downregulated (0.815 ± 0.295 vs. 0.258 ± 0.130, P = 0.0308). PI3K (0.365 ± 0.142 vs. 0.763 ± 0.013, P = 0.0475), pAKT (0.493 ± 0.159 vs. 1.183 ± 0.344, P = 0.0254) and pmTOR (0.509 ± 0.088 vs. 1.110 ± 0.190, P = 0.0368) protein expression levels were upregulated in TA muscle. Meanwhile, vitamin K1 attenuated serum inflammatory factor levels.
CONCLUSIONS
Vitamin K1 might ameliorate LPS-triggered skeletal muscle damage by antagonizing NF-κB-mediated inflammation through upregulation of SIRT1 and regulating the balance between protein synthesis and catabolism.
Topics: Humans; Mice; Animals; Fecal Microbiota Transplantation; Lipopolysaccharides; Sirtuin 1; Vitamin K 1; Inflammation; Sepsis; Muscle, Skeletal; Muscle Weakness
PubMed: 38018317
DOI: 10.1002/jcsm.13379 -
Nutrients Dec 2023The present review deals with two main ingredients of energy/power drinks: B vitamins and glucuronolactone and their possible effect on the immune system. There is a... (Review)
Review
The present review deals with two main ingredients of energy/power drinks: B vitamins and glucuronolactone and their possible effect on the immune system. There is a strong relationship between the recommended daily dose of selected B vitamins and a functional immune system. Regarding specific B vitamins: (1) Riboflavin is necessary for the optimization of reactive oxygen species (ROS) in the fight against bacterial infections caused by and . (2) Niacin administered within normal doses to obese rats can change the phenotype of skeletal fibers, and thereby affect muscle metabolism. This metabolic phenotype induced by niacin treatment is also confirmed by stimulation of the expression of genes involved in the metabolism of free fatty acids (FFAs) and oxidative phosphorylation at this level. (3) Vitamin B5 effects depend primarily on the dose, thus large doses can cause diarrhea or functional disorders of the digestive tract whereas normal levels are effective in wound healing, liver detoxification, and joint health support. (4) High vitamin B6 concentrations (>2000 mg per day) have been shown to exert a significant negative impact on the dorsal root ganglia. Whereas, at doses of approximately 70 ng/mL, sensory symptoms were reported in 80% of cases. (5) Chronic increases in vitamin B12 have been associated with the increased incidence of solid cancers. Additionally, glucuronolactone, whose effects are not well known, represents a controversial compound. (6) Supplementing with D-glucarates, such as glucuronolactone, may help the body's natural defense system function better to inhibit different tumor promoters and carcinogens and their consequences. Cumulatively, the present review aims to evaluate the relationship between the selected B vitamins group, glucuronolactone, and the immune system and their associations to bioavailability, doses, and efficiency.
Topics: Animals; Rats; Vitamin B Complex; Niacin; Biological Availability; Glucuronates; Vitamin A; Vitamin K; Carcinogens
PubMed: 38201854
DOI: 10.3390/nu16010024 -
International Journal of Surgery... Dec 2023Due to the high individual variability of anticoagulant warfarin, this study aimed to investigate the effects of vitamin K concentration and gut microbiota on individual...
BACKGROUND AND OBJECTIVES
Due to the high individual variability of anticoagulant warfarin, this study aimed to investigate the effects of vitamin K concentration and gut microbiota on individual variability of warfarin in 246 cardiac surgery patients.
METHODS
The pharmacokinetics and pharmacodynamics (PKPD) model predicted international normalized ratio (INR) and warfarin concentration. Serum and fecal samples were collected to detect warfarin and vitamin K [VK1 and menaquinone-4 (MK4)] concentrations and gut microbiota diversity, respectively. In addition, the patient's medical records were reviewed for demographic characteristics, drug history, and CYP2C9, VKORC1, and CYP4F2 genotypes.
RESULTS
The PKPD model predicted ideal values of 62.7% for S-warfarin, 70.4% for R-warfarin, and 76.4% for INR. The normal VK1 level was 1.34±1.12 nmol/ml (95% CI: 0.33-4.08 nmol/ml), and the normal MK4 level was 0.22±0.18 nmol/ml (95% CI: 0.07-0.63 nmol/ml). The MK4 to total vitamin K ratio was 16.5±9.8% (95% CI: 4.3-41.5%). The S-warfarin concentration of producing 50% of maximum anticoagulation and the half-life of prothrombin complex activity tended to increase with vitamin K. Further, Prevotella and Eubacterium of gut microbiota identified as the main bacteria associated with individual variability of warfarin. The results suggest that an increase in vitamin K concentration can decrease anticoagulation, and gut microbiota may influence warfarin anticoagulation through vitamin K2 synthesis.
CONCLUSION
This study highlights the importance of considering vitamin K concentration and gut microbiota when prescribing warfarin. The findings may have significant implications for the personalized use of warfarin. Further research is needed to understand better the role of vitamin K and gut microbiota in warfarin anticoagulation.
Topics: Humans; Warfarin; Vitamin K; Gastrointestinal Microbiome; Cytochrome P450 Family 4; Vitamin K Epoxide Reductases; Anticoagulants; Genotype; Cardiac Surgical Procedures
PubMed: 37598356
DOI: 10.1097/JS9.0000000000000673 -
Nature Reviews. Urology Oct 2023Calcium-based kidney stone disease is a highly prevalent and morbid condition, with an often complicated and multifactorial aetiology. An abundance of research on the... (Review)
Review
Calcium-based kidney stone disease is a highly prevalent and morbid condition, with an often complicated and multifactorial aetiology. An abundance of research on the role of specific vitamins (B, C and D) in stone formation exists, but no consensus has been reached on how these vitamins influence stone disease. As a consequence of emerging research on the role of the gut microbiota in urolithiasis, previous notions on the contribution of these vitamins to urolithiasis are being reconsidered in the field, and investigation into previously overlooked vitamins (A, E and K) was expanded. Understanding how the microbiota influences host vitamin regulation could help to determine the role of vitamins in stone disease.
Topics: Humans; Vitamins; Calcium; Gastrointestinal Microbiome; Kidney Calculi; Urolithiasis; Vitamin A; Vitamin K
PubMed: 37161031
DOI: 10.1038/s41585-023-00768-5 -
Nutrients Oct 2023Cataract, defined as the opacification of the lens that prevents clear vision, is a leading cause of vision loss and impairment worldwide. Elderly people comprise the... (Review)
Review
Cataract, defined as the opacification of the lens that prevents clear vision, is a leading cause of vision loss and impairment worldwide. Elderly people comprise the highest proportion of those suffering from this eye disease. According to the National Institute of Health (NIH), the risk of developing aged-related cataract (ARC) increases with every decade of life, starting from the age of 40. Despite progress in surgical treatment methods, life-style modifications may be beneficial in prevention or slowing down the progression of ARC. This systematic review aims to summarize studies on the significance of specific nutritional patterns, dietary products, vitamins, minerals, and carotenoids intake in the onset or progression of ARC. In this context, the presented paper thoroughly analyzes 24 articles, following the PRISMA guidelines. The results indicate significant protective effects of various dietary patterns, including the Korean balanced diet, vegetarian diet, "dairy products and vegetables", "traditional", "antioxidant", and "omega-3" patterns. Additionally, the consumption of fruits, vegetables, legumes, nuts, skimmed yoghurt, fish, coffee, and vitamins has shown positive effects on cataract incidence. Therefore, further research seems to be essential to gain a better understanding of these associations and to create uniform dietary recommendations for both the vulnerable population and ARC patients.
Topics: Aged; Animals; Humans; Vitamins; Diet; Cataract; Antioxidants; Vitamin A; Vegetables; Vitamin K
PubMed: 37960238
DOI: 10.3390/nu15214585 -
Genome Medicine Jan 2024The impact of the gut microbiome on the initiation and intensity of immune-related adverse events (irAEs) prompted by immune checkpoint inhibitors (ICIs) is widely...
BACKGROUND
The impact of the gut microbiome on the initiation and intensity of immune-related adverse events (irAEs) prompted by immune checkpoint inhibitors (ICIs) is widely acknowledged. Nevertheless, there is inconsistency in the gut microbial associations with irAEs reported across various studies.
METHODS
We performed a comprehensive analysis leveraging a dataset that included published microbiome data (n = 317) and in-house generated data from 16S rRNA and shotgun metagenome samples of irAEs (n = 115). We utilized a machine learning-based approach, specifically the Random Forest (RF) algorithm, to construct a microbiome-based classifier capable of distinguishing between non-irAEs and irAEs. Additionally, we conducted a comprehensive analysis, integrating transcriptome and metagenome profiling, to explore potential underlying mechanisms.
RESULTS
We identified specific microbial species capable of distinguishing between patients experiencing irAEs and non-irAEs. The RF classifier, developed using 14 microbial features, demonstrated robust discriminatory power between non-irAEs and irAEs (AUC = 0.88). Moreover, the predictive score from our classifier exhibited significant discriminative capability for identifying non-irAEs in two independent cohorts. Our functional analysis revealed that the altered microbiome in non-irAEs was characterized by an increased menaquinone biosynthesis, accompanied by elevated expression of rate-limiting enzymes menH and menC. Targeted metabolomics analysis further highlighted a notably higher abundance of menaquinone in the serum of patients who did not develop irAEs compared to the irAEs group.
CONCLUSIONS
Our study underscores the potential of microbial biomarkers for predicting the onset of irAEs and highlights menaquinone, a metabolite derived from the microbiome community, as a possible selective therapeutic agent for modulating the occurrence of irAEs.
Topics: Humans; Neoplasms; Immune Checkpoint Inhibitors; Gastrointestinal Microbiome; Antineoplastic Agents, Immunological; RNA, Ribosomal, 16S; Vitamin K 2; Drug-Related Side Effects and Adverse Reactions; Immunotherapy; Programmed Cell Death 1 Receptor; Immune System Diseases; Retrospective Studies; Lung Neoplasms
PubMed: 38243343
DOI: 10.1186/s13073-024-01285-9 -
Revista Brasileira de Ginecologia E... Nov 2023It is well known that female infertility is multifactorial. Therefore, we aimed to compare the effects of thyroid dysfunction, vitamin deficiency, and microelement...
OBJECTIVE
It is well known that female infertility is multifactorial. Therefore, we aimed to compare the effects of thyroid dysfunction, vitamin deficiency, and microelement deficiency in fertile and infertile patients.
MATERIALS AND METHODS
Between May 1st, 2017, and April 1st, 2019, we conducted a retrospective case-control study with of 380 infertile and 346 pregnant patients (who normally fertile and able to conceive spontaneously). The fertile patients were selected among those who got pregnant spontaneously without treatment, had a term birth, and did not have systemic or obstetric diseases. The levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), anti-thyroid peroxidase (anti-TPO), vitamin D, vitamin B12, folic acid, ferritin, and zinc of both groups were compared.
RESULTS
There was no difference between patients in the infertile and pregnant groups in terms of low normal and high serum T3 and T4 levels ( = 0.938; > 0.05) respectively, nor in terms of normal and high anti-TPO levels ( = 0.182; > 0.05) respectively. There was no significant difference regarding patients with low, insufficient, and sufficient vitamin D levels in the infertile and pregnant groups ( = 0.160; >0.05) respectively. The levels of folic acid, ferritin, and zinc of the infertile group were significantly lower than those of the pregnant group.
CONCLUSION
The serum levels of folic acid, ferritin, and zinc in infertile patients presenting to our outpatient clinic were lower than those o the fertile patients.
Topics: Pregnancy; Humans; Female; Vitamins; Infertility, Female; Retrospective Studies; Case-Control Studies; Thyroid Hormones; Vitamin D; Vitamin A; Vitamin K; Folic Acid; Ferritins; Zinc
PubMed: 38029770
DOI: 10.1055/s-0043-1772478 -
International Journal of Molecular... Jan 2024Vitamin K (VK), a fat‑soluble vitamin, is well known as an anticoagulant in the clinic. It is essential for the post‑translational activation of VK‑dependent... (Review)
Review
Vitamin K (VK), a fat‑soluble vitamin, is well known as an anticoagulant in the clinic. It is essential for the post‑translational activation of VK‑dependent proteins (VKDPs) because hydroquinone VK is a cofactor of glutamine carboxylase. At present, 17 VKDPs are known, which are mainly involved in coagulation and calcification. When Glu residues are carboxylated to Gla residues, these proteins gain a higher calcium‑binding ability, which explains why VK has an important role in blood coagulation and biomineralization. However, the current view on the role of VK and several VKDPs in biomineralization remains inconsistent. For instance, conflicting results have been reported regarding the effect of gene knockout on the bone of mice; matrix Gla protein (MGP) promotes osteoblasts mineralization but inhibits vascular smooth muscle cell mineralization. The present review aimed to summarize the existing evidence that several VKDPs, including osteocalcin, MGP, Gla‑rich protein and growth arrest specific 6 are closely related to calcification, including bone health, vascular calcification and lithiasis. The current review discussed these controversies and provided suggestions for future studies on VKDPs, i.e. taking into account dietary habits, geographical environments and genetic backgrounds.
Topics: Mice; Animals; Vitamin K; Osteocalcin; Biomineralization; Calcium-Binding Proteins; Extracellular Matrix Proteins; Vascular Calcification; Bone and Bones
PubMed: 37997858
DOI: 10.3892/ijmm.2023.5330 -
BMJ Open Sep 2023COVID-19 has caused morbidity, hospitalisation and mortality worldwide. Despite effective vaccines, there is still a need for effective treatments, especially for people... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
COVID-19 has caused morbidity, hospitalisation and mortality worldwide. Despite effective vaccines, there is still a need for effective treatments, especially for people in the community. Dietary supplements have long been used to treat respiratory infections, and preliminary evidence indicates some may be effective in people with COVID-19. We sought to evaluate whether a combination of vitamin C, vitamin D, vitamin K and zinc could improve overall health and decrease symptom burden in outpatients diagnosed with COVID-19.
METHODS
Participants were randomised to receive either vitamin C (6 g), vitamin D (1000 units), vitamin K (240 μg) and zinc acetate (75 mg) or placebo daily for 21 days and were followed for 12 weeks. An additional loading dose of 50 000 units vitamin D (or placebo) was given on day one. The primary outcome was participant-reported overall health using the EuroQol Visual Assessment Scale summed over 21 days. Secondary outcomes included health status, symptom severity, symptom duration, delayed return to usual health, frequency of hospitalisation and mortality.
RESULTS
90 patients (46 control, 44 treatment) were randomised. The study was stopped prematurely due to insufficient capacity for recruitment. The mean difference (control-treatment) in cumulative overall health was -37.4 (95% CI -157.2 to 82.3), p=0.53 on a scale of 0-2100. No clinically or statistically significant differences were seen in any secondary outcomes.
INTERPRETATION
In this double-blind, placebo-controlled, randomised trial of outpatients diagnosed with COVID-19, the dietary supplements vitamin C, vitamin D, vitamin K and zinc acetate showed no clinically or statistically significant effects on the documented measures of health compared with a placebo when given for 21 days. Termination due to feasibility limited our ability to demonstrate the efficacy of these supplements for COVID-19. Further research is needed to determine clinical utility.
TRIAL REGISTRATION NUMBER
NCT04780061.
Topics: Humans; SARS-CoV-2; COVID-19; Zinc Acetate; Dietary Supplements; Vitamins; Ascorbic Acid; Cholecalciferol; Vitamin K 2
PubMed: 37739466
DOI: 10.1136/bmjopen-2023-073761 -
International Journal of Molecular... Mar 2024One mechanism to regulate pathological vascular calcification (VC) is its active inhibition. Loss or inactivation of endogenic inhibitors is a major inductor of VC. Such... (Review)
Review
One mechanism to regulate pathological vascular calcification (VC) is its active inhibition. Loss or inactivation of endogenic inhibitors is a major inductor of VC. Such inhibitors are proteins rich in gamma-glutamyl residues (Gla-proteins), whose function strongly depends on vitamin K. The current narrative review is focused on discussing the role of extrahepatic vitamin K-dependent Gla-proteins (osteocalcin, OC; matrix Gla-protein, MGP; Gla-rich protein, GRP) in cardio-vascular pathology. Gla-proteins possess several functionally active forms whose role in the pathogenesis of VC is still unclear. It is assumed that low circulating non-phosphorylated MGP is an indicator of active calcification and could be a novel biomarker of prevalent VC. High circulating completely inactive MGP is proposed as a novel risk factor for cardio-vascular events, disease progression, mortality, and vitamin K deficiency. The ratio between uncarboxylated (ucOC) and carboxylated (cOC) OC is considered as an indicator of vitamin K status indirectly reflecting arterial calcium. Despite the evidence that OC is an important energy metabolic regulator, its role on global cardio-vascular risk remains unclear. GRP acts as a molecular mediator between inflammation and calcification and may emerge as a novel biomarker playing a key role in these processes. Gla-proteins benefit clinical practice as inhibitors of VC, modifiable by dietary factors.
Topics: Humans; Osteocalcin; Vitamin K; Calcium-Binding Proteins; Extracellular Matrix Proteins; Vascular Calcification; Cardiovascular Diseases; Biomarkers
PubMed: 38542487
DOI: 10.3390/ijms25063517