The Potential of Vitamin K as a Regulatory Factor of Bone Metabolism—A Review

Wang, Huakai; Ma, Yongxi

doi:10.3390/nu15234935

Cited by 4 publications

(1 citation statement)

References 99 publications

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“…The human vitamin K epoxide reductase (hVKORC1), an endoplasmic reticulum (ER) protein, reduces inactive vitamin K 2,3-epoxide to active vitamin K quinone, required for blood coagulation [1][2][3][4]. Four functional cysteine residues of hVKORC1 control all steps of its repeatedly reproduced enzymatic cycle.…”

Section: Introductionmentioning

confidence: 99%

Synergy of Mutation-Induced Effects in Human Vitamin K Epoxide Reductase: Perspectives and Challenges for Allo-Network Modulator Design

Botnari,

Tchertanov

2024

IJMS

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The human Vitamin K Epoxide Reductase Complex (hVKORC1), a key enzyme transforming vitamin K into the form necessary for blood clotting, requires for its activation the reducing equivalents delivered by its redox partner through thiol-disulfide exchange reactions. The luminal loop (L-loop) is the principal mediator of hVKORC1 activation, and it is a region frequently harbouring numerous missense mutations. Four L-loop hVKORC1 mutants, suggested in vitro as either resistant (A41S, H68Y) or completely inactive (S52W, W59R), were studied in the oxidised state by numerical approaches (in silico). The DYNASOME and POCKETOME of each mutant were characterised and compared to the native protein, recently described as a modular protein composed of the structurally stable transmembrane domain (TMD) and the intrinsically disordered L-loop, exhibiting quasi-independent dynamics. The DYNASOME of mutants revealed that L-loop missense point mutations impact not only its folding and dynamics, but also those of the TMD, highlighting a strong mutation-specific interdependence between these domains. Another consequence of the mutation-induced effects manifests in the global changes (geometric, topological, and probabilistic) of the newly detected cryptic pockets and the alternation of the recognition properties of the L-loop with its redox protein. Based on our results, we postulate that (i) intra-protein allosteric regulation and (ii) the inherent allosteric regulation and cryptic pockets of each mutant depend on its DYNASOME; and (iii) the recognition of the redox protein by hVKORC1 (INTERACTOME) depend on their DYNASOME. This multifaceted description of proteins produces “omics” data sets, crucial for understanding the physiological processes of proteins and the pathologies caused by alteration of the protein properties at various “omics” levels. Additionally, such characterisation opens novel perspectives for the development of “allo-network drugs” essential for the treatment of blood disorders.

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Section: Introductionmentioning

confidence: 99%

Synergy of Mutation-Induced Effects in Human Vitamin K Epoxide Reductase: Perspectives and Challenges for Allo-Network Modulator Design

Botnari,

Tchertanov

2024

IJMS

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Prediction of Osteoporotic Hip Fracture Outcome: Comparative Accuracy of 27 Immune–Inflammatory–Metabolic Markers and Related Conceptual Issues

Fisher,

Srikusalanukul

2024

JCM

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Objectives: This study, based on the concept of immuno-inflammatory–metabolic (IIM) dysregulation, investigated and compared the prognostic impact of 27 indices at admission for prediction of postoperative myocardial injury (PMI) and/or hospital death in hip fracture (HF) patients. Methods: In consecutive HF patient (n = 1273, mean age 82.9 ± 8.7 years, 73.5% females) demographics, medical history, laboratory parameters, and outcomes were recorded prospectively. Multiple logistic regression and receiver-operating characteristic analyses (the area under the curve, AUC) were used to establish the predictive role for each biomarker. Results: Among 27 IIM biomarkers, 10 indices were significantly associated with development of PMI and 16 were indicative of a fatal outcome; in the subset of patients aged >80 years with ischaemic heart disease (IHD, the highest risk group: 90.2% of all deaths), the corresponding figures were 26 and 20. In the latter group, the five strongest preoperative predictors for PMI were anaemia (AUC 0.7879), monocyte/eosinophil ratio > 13.0 (AUC 0.7814), neutrophil/lymphocyte ratio > 7.5 (AUC 0.7784), eosinophil count < 1.1 × 109/L (AUC 0.7780), and neutrophil/albumin × 10 > 2.4 (AUC 0.7732); additionally, sensitivity was 83.1–75.4% and specificity was 82.1–75.0%. The highest predictors of in-hospital death were platelet/lymphocyte ratio > 280.0 (AUC 0.8390), lymphocyte/monocyte ratio < 1.1 (AUC 0.8375), albumin < 33 g/L (AUC 0.7889), red cell distribution width > 14.5% (AUC 0.7739), and anaemia (AUC 0.7604), sensitivity 88.2% and above, and specificity 85.1–79.3%. Internal validation confirmed the predictive value of the models. Conclusions: Comparison of 27 IIM indices in HF patients identified several simple, widely available, and inexpensive parameters highly predictive for PMI and/or in-hospital death. The applicability of IIM biomarkers to diagnose and predict risks for chronic diseases, including OP/OF, in the preclinical stages is discussed.

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Investigating the Effects and Mechanisms of Combined Vitamin D and K Supplementation in Postmenopausal Women: An Up-to-Date Comprehensive Review of Clinical Studies

Rusu,

Bigman,

Ryan

et al. 2024

Nutrients

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Aging is a complex process and a significant risk factor for chronic diseases. Menopause, a component of aging in women, is associated with several important cardiometabolic conditions including metabolic syndrome, osteoporosis, and cardiovascular diseases. Menopausal women could benefit from preventative strategies that may decrease morbidity and mortality and improve their quality of life. Vitamins D and K are essential nutrients required for bone health, immune function, and reducing cardiovascular risks, yet their synergistic effect is less understood in aging women. This is the first comprehensive review to summarize the evidence found in randomized clinical trials of the beneficial effects of vitamin D and K co-treatment in postmenopausal women. In our literature search across key electronic databases such as Cochrane, PubMed, and Ovid, we identified 31 pertinent studies. Overall, significant findings indicate that the combined intake of vitamins D and K may positively affect cardiovascular and bone health in postmenopausal women, emphasizing the importance of maintaining a healthy diet rich in vegetables and fermented dairy products. Given the challenges in obtaining all necessary nutrients solely through the diet, vitamin D and K supplements are recommended for postmenopausal women to promote healthy aging and well-being.

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The Potential of Vitamin K as a Regulatory Factor of Bone Metabolism—A Review

Cited by 4 publications

References 99 publications

Synergy of Mutation-Induced Effects in Human Vitamin K Epoxide Reductase: Perspectives and Challenges for Allo-Network Modulator Design

Synergy of Mutation-Induced Effects in Human Vitamin K Epoxide Reductase: Perspectives and Challenges for Allo-Network Modulator Design

Prediction of Osteoporotic Hip Fracture Outcome: Comparative Accuracy of 27 Immune–Inflammatory–Metabolic Markers and Related Conceptual Issues

Investigating the Effects and Mechanisms of Combined Vitamin D and K Supplementation in Postmenopausal Women: An Up-to-Date Comprehensive Review of Clinical Studies

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