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Treatment to reduce vascular calcification in hemodialysis patients using vitamin K (Trevasc-HDK): A study protocol for a randomized controlled trial.

INTRODUCTION: End stage renal failure patients on hemodialysis have significant vascular calcification This is postulated to be related to sub-clinical vitamin K deficiency, which is prevalent in hemodialysis patients. Vitamin K deficiency result in the failure of the matrix GLA protein (MGP) to undergo carboxylation. MGP is a natural local inhibitor of vascular calcification and the lack of functional carboxylated MGP may contribute to increase vascular calcification. Vitamin K supplement should therefore correct this anomaly and decrease the rate or severity of vascular calcification in this…

Vascular calcification relationship to vascular biomarkers and bone metabolism in advanced chronic kidney disease.

BACKGROUND: Vascular calcification (VC) and renal osteodystrophy are important complications of advanced chronic kidney disease (CKD). High … (rho = 0.32, p < 0.05), osteoprotegerin (rho = 0.40, p = 0.001) and dephosphorylated-uncarboxylated matrix Gla protein (rho = 0.31, p < 0.05). LLAC in CKD also correlated with worse distal tibia cortical bone mineral density, thickness and porosity. No association was found between LLAC and bone turnover, mineralization or volume on biopsy in CKD. In multivariate an …

Serum osteocalcin is increased in patients with osteomalacia: correlations with biochemical and histomorphometric findings.

The synthesis of osteocalcin or bone gla protein by osteoblasts is markedly stimulated by 1,25-(OH)2D, a key hormone in the regulation of bone mineralization. The circulating levels of osteocalcin have been shown to reflect both the osteoid matrix production and the formation rate of mineralized bone in several metabolic bone diseases (osteoporosis, thyrotoxicosis, primary hyperparathyroidism) in which both mechanisms are tightly coupled because of the absence of mineralization defect. In this study, we measured in 12 patients (7 women, 5 men, 56 +/- 15 yr old) with untreated osteomalacia seru

Effects of long-term vitamin K(1) (phylloquinone) or vitamin K(2) (menaquinone-4) supplementation on body composition and serum parameters in rats.

Vitamin K is a cofactor for γ-glutamyl carboxylase, which is an essential enzyme for the γ-carboxylation of vitamin K-dependent proteins such as osteocalcin and matrix Gla protein. Although it has been suggested that vitamin K plays an important role in the improvement of bone metabolism, the relationship between dietary vitamin K intake and bone metabolism has not been thoroughly investigated. Moreover, vitamin K is thought to have other actions beyond influencing the γ-carboxylation status. In the present study, we examined the effects of the long-term addition of phylloquinone (PK) or menaq…

[Effect of ultrasonic curettage combined with sodium hyaluronate gel on chronic periodontitis and its effect on inflammatory factors hs-CRP, MCP-1 and MMP-13 in gingival crevicular fluid].

PURPOSE: To investigate the effect of ultrasonic curettage combined with sodium hyaluronate gel in the treatment of chronic periodontitis (CP) and the effect on inflammatory factor hypersensitive C-reactive protein (hs-CRP), monocyte chemotactic protein 1 (MCP-1) and matrix metalloproteinase 13 (MMP-13) in gingival crevicular fluid. METHODS: A total of 102 patients with CP from October 2021 to October 2022 were selected, divided into experimental group (n=51) and control group (n=51) by random number table method. The control group received ultrasonic subgingival curetage, and the experimenta

Evaluation of trabecular meshwork-specific promoters in vitro and in vivo using scAAV2 vectors expressing C3 transferase.

AIM: To evaluate the potential of two trabecular meshwork (TM)-specific promoters, Chitinase 3-like 1 (Ch3L1) and matrix gla protein (MGP), for improving specificity and safety in glaucoma gene therapy based on self-complementary AAV2 (scAAV2) vector technologies. METHODS: An scAAV2 vector with C3 transferase (C3) as the reporter gene (scAAV2-C3) was selected. The scAAV2-C3 vectors were driven by Ch3L1 (scAAV2-Ch3L1-C3), MGP (scAAV2-MGP-C3), enhanced MGP (scAAV2-eMGP-C3) and cytomegalovirus (scAAV2-CMV-C3), respectively. The cultured primary human TM cells were treated with each vector at dif…

Characterization of vitamin K-dependent carboxylase mutations that cause bleeding and nonbleeding disorders.

Vitamin K-dependent coagulation factors deficiency is a bleeding disorder mainly associated with mutations in γ-glutamyl carboxylase (GGCX) that often has fatal outcomes. Some patients with nonbleeding syndromes linked to GGCX mutations, however, show no coagulation abnormalities. The correlation between GGCX genotypes and their clinical phenotypes has been previously unknown. Here we report the identification and characterization of novel GGCX mutations in a patient with both severe cerebral bleeding disorder and comorbid Keutel syndrome, a nonbleeding malady caused by functional defects of m

Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial.

BACKGROUND: Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis. METHODS: In a randomized, double-blind, multicenter trial, men from the community with an AVC score >300 arbitrary units (AU) on cardiac noncontrast computer tomography were randomized to daily treatment with tablet 720 µg MK-7 plus 25 µg vitamin D or matching placebo for 24 months. The primary outcome was the ch

Real-world data from a national survey on management of CKD-associated osteoporosis among Italian nephrologists.

UNLABELLED: Chronic kidney disease (CKD)-associated osteoporosis increases fracture risk, yet clinical guidance remains unclear. A survey of … e in 92-100% of their reference laboratories. Measurements for fibroblast growth factor-23, Klotho, Matrix Gla protein, procollagen type 1 N-terminal propeptide, and tartrate-resistant acid phosphatase 5b were available in 64-74% of cases. Regarding PTH cut-off values, 47.2% followed KDOQI and 43.8% followed KDIGO recommendations. Vitamin D was widely used across CK …

Inflammation-mediated vitamin K and vitamin D effects on vascular calcifications in people with HIV on active antiretroviral therapy.

BACKGROUND: People with HIV (PWH) experience increased systemic inflammation and monocyte activation, leading to increased risk of cardiovas … of 25-hydroxyvitamin D (vitamin D) and inactive vitamin K-dependent dephosphorylated-uncarboxylated matrix Gla protein (dp-uc MGP, marker of vitamin K deficiency) were measured in plasma during a fasting state. The relationship between inflammation markers, dp-uc MGP, and vitamin D on CACs were estimated using zero-inflated negative binomial regression. Adjusted mod …

Full-length merozoite surface protein 1 formulated with GLA-SE adjuvant in malaria pre-exposed adults: a randomised, controlled, double-blind, parallel-group, single-centre Phase Ib trial.

BACKGROUND: A highly effective blood-stage malaria vaccine targeting the merozoite surface protein 1 (MSP1) of Plasmodium falciparum (Pf) might complement the imperfect protection conferred by the currently available first-generation pre-erythrocytic malaria vaccines RTS,S/AS01E and R21/Matrix-M. We investigated for the first time the safety, reactogenicity and immunogenicity of full-length recombinant PfMSP1 (MSP1FL) formulated in Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE) adjuvant as a malaria vaccine in a malaria pre-exposed adult population. METHODS: We conducted a randomized,

Potential Targeting Mechanisms for Bone-Directed Therapies.

Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. Howe

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… Gla-Containing Proteins Gla-containing proteins are posttranslationally modified by vitamin K-dependent enzymes, including osteocalcin (OCN) and matrix Gla protein. … Matrix Gla protein (MGP), a vitamin K-dependent protein, is more prevalent in cartilage than in bone, and its expression begins in the early stage of development and remains at the same level throughout life [ 35 ]. …

Exploring the genetic alterations of Gorham-Stout disease.

The "vanishing bone disease" or Gorham-Stout disease (GSD) is a very rare disorder characterized by massive lymphatic and angiomatous proliferation accompanied by progressive osteolysis, without the deposition of new bone matrix. Because of its rare and complex clinical features, diagnosis is challenging and its etiopathogenesis is not completely known; the genetic basis of GSD has been hypothesized and different mutations have been reported in patients. Our review aims to describe all these genetic alterations found in GSD patients and their association with clinical features. The identificat

N-3 Long-Chain Polyunsaturated Fatty Acids, Eicosapentaenoic and Docosahexaenoic Acid, and the Role of Supplementation during Cancer Treatment: A Scoping Review of Current Clinical Evidence.

This scoping review examines the evidence for n-3 long-chain polyunsaturated fatty acid [LCPUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] supplementation in clinical cancer therapy. A comprehensive literature search was performed to identify relevant clinical intervention studies conducted through August 2020. Fifty-seven unique cancer trials, assessing EPA and/or DHA supplementation pre- or post-treatment, concomitant with neoadjuvant chemotherapy, radiation or surgery, or in palliative therapy were included. Breast, head and neck, gastrointestinal, gastric, colorectal/rect

The epigenetic potential of vitamin K2 in brain health.

Vitamin K2 refers to a subfamily of vitamin K isoforms known as Menaquinones and, therefore, indicated as MK-n, the "n" indicating the number of isoprene units present in the side chain. Like the other members of the Vitamin K family, K2 is an enzymatic cofactor for the γ-glutamyl carboxylase (GGCX). This enzyme's substrates, which carboxylate glutamic acid residues, are known as Vitamin K-dependent proteins (VKDPs). Besides being involved in bone homeostasis, vitamin K exerts its primary function in the coagulation process. More recently, a function of Vitamin K also in brain homeostasis has

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… Beyond the well-known VKDPs involved in coagulation, key extrahepatic VKDPs include osteocalcin (OCN), which plays a critical role in bone mineralization, and matrix Gla-protein (MGP), a powerful inhibitor of vascular calcification. … Based on these data, several studies have highlighted the beneficial role of vitamin K2 supplementation in vascular health and arterial stiffness prevention, mainly via downregulation of circulating dephosphorylated, uncarboxylated Matrix Gla protein (dp-ucMGP) [ 52 , 53 ]. …

Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies.

A biomarker is an analyte indicating the presence of a biological process linked to the clinical manifestations and outcome of a particular disease. In the case of lysosomal storage disorders (LSDs), primary and secondary accumulating metabolites or proteins specifically secreted by storage cells are good candidates for biomarkers. Clinical applications of biomarkers are found in improved diagnosis, monitoring disease progression, and assessing therapeutic correction. These are illustrated by reviewing the discovery and use of biomarkers for Gaucher disease and Fabry disease. In addition, rece

Inflammation in Cardiomyopathies: Cellular Mechanisms Across Cardiac Phenotype.

Cardiomyopathies are traditionally classified by structural and genetic phenotypes, but emerging evidence highlights chronic myocardial inflammation as a pivotal driver of disease progression across different etiologies. This review synthesizes the current literature on the cellular and molecular inflammatory mechanisms underlying hypertrophic cardiomyopathy, Anderson-Fabry disease, cardiac amyloidosis, arrhythmogenic cardiomyopathy, and dilated cardiomyopathy. Across these distinct conditions, endogenous triggers such as metabolic substrates, misfolded amyloid fibrils, mechanical stress, or v

Treatment of bone metastases from breast cancer with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD).

Twenty-eight patients with progressive symptomatic bone metastases from breast cancer received (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) 30 mg in 500 ml of 0.9% saline infused over 2 h every 14 days. No other systemic therapy for breast cancer was prescribed. All patients had progressed on at least one previous systemic treatment. APD was continued until the disease progressed. Patients were assessed for objective response by the UICC criteria. In addition, subjective response was determined by a pain questionnaire. Radiological evidence of bone healing with sclerosis of lytic di

Molecular Mechanisms of Bone Metastasis: Which Targets Came from the Bench to the Bedside?

Bone metastases ultimately result from a complex interaction between cancer cells and bone microenvironment. However, prior to the colonization of the bone, cancer cells must succeed through a series of steps that will allow them to detach from the primary tumor, enter into circulation, recognize and adhere to specific endothelium, and overcome dormancy. We now know that as important as the metastatic cascade, tumor cells prime the secondary organ microenvironment prior to their arrival, reflecting the existence of specific metastasis-initiating cells in the primary tumor and circulating osteo

Left Ventricular Hypertrophy: Etiology-Based Therapeutic Options.

Determining the etiologies of left ventricular hypertrophy (LVH) can be challenging due to the similarities of the different manifestations in clinical presentation and morphological features. Depending on the underlying cause, not only left ventricular mass but also left ventricular cavity size, or both, may increase. Patients with LVH remain asymptomatic for a few years, but disease progression will lead to the development of systolic or diastolic dysfunction and end-stage heart failure. As hypertrophied cardiac muscle disrupts normal conduction, LVH predisposes to arrhythmias. Distinguishin