Editorial

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Open AccessEditorial

Vitamin D and Vitamin D-Binding Protein in Health and Disease

by Charlotte Delrue and Marijn M. Speeckaert

Int. J. Mol. Sci. 2023, 24(5), 4642; https://doi.org/10.3390/ijms24054642 - 28 Feb 2023

Cited by 6 | Viewed by 3976

Abstract

Vitamin D is a fat-soluble secosteroid that exists in two forms: vitamin D₂ and vitamin D₃ [...] Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease)

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Research

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25 pages, 5374 KiB

Open AccessArticle

Analysis of the Biological Properties of Blood Plasma Protein with GcMAF Functional Activity

by Evgeniya V. Dolgova, Svetlana S. Kirikovich, Evgeniy V. Levites, Vera S. Ruzanova, Anastasia S. Proskurina, Genrikh S. Ritter, Oleg S. Taranov, Nikolay A. Varaksin, Tatiana G. Ryabicheva, Olga Yu. Leplina, Alexandr A. Ostanin, Elena R. Chernykh and Sergey S. Bogachev

Int. J. Mol. Sci. 2022, 23(15), 8075; https://doi.org/10.3390/ijms23158075 - 22 Jul 2022

Cited by 4 | Viewed by 2027

Abstract

The main problem related to the studies focusing on group-specific component protein-derived macrophage-activating factor (GcMAF) is the lack of clarity about changes occurring in different types of macrophages and related changes in their properties under the effect of GcMAF in various clinical conditions. [...] Read more.

The main problem related to the studies focusing on group-specific component protein-derived macrophage-activating factor (GcMAF) is the lack of clarity about changes occurring in different types of macrophages and related changes in their properties under the effect of GcMAF in various clinical conditions. We analyzed the antitumor therapeutic properties of GcMAF in a Lewis carcinoma model in two clinical conditions: untreated tumor lesion and tumor resorption after exposure to Karanahan therapy. GcMAF is formed during site-specific deglycosylation of vitamin D3 binding protein (DBP). DBP was obtained from the blood of healthy donors using affinity chromatography on a column with covalently bound actin. GcMAF-related factor (GcMAF-RF) was converted in a mixture with induced lymphocytes through the cellular enzymatic pathway. The obtained GcMAF-RF activates murine peritoneal macrophages (p < 0.05), induces functional properties of dendritic cells (p < 0.05) and promotes in vitro polarization of human M0 macrophages to M1 macrophages (p < 0.01). Treatment of whole blood cells with GcMAF-RF results in active production of both pro- and anti-inflammatory cytokines. It is shown that macrophage activation by GcMAF-RF is inhibited by tumor-secreted factors. In order to identify the specific antitumor effect of GcMAF-RF-activated macrophages, an approach to primary reduction of humoral suppressor activity of the tumor using the Karanahan therapy followed by macrophage activation in the tumor-associated stroma (TAS) was proposed. A prominent additive effect of GcMAF-RF, which enhances the primary immune response activation by the Karanahan therapy, was shown in the model of murine Lewis carcinoma. Inhibition of the suppressive effect of TAS is the main condition required for the manifestation of the antitumor effect of GcMAF-RF. When properly applied in combination with any chemotherapy, significantly reducing the humoral immune response at the advanced tumor site, GcMAF-RF is a promising antitumor therapeutic agent that additively destroys the pro-tumor properties of macrophages of the tumor stroma. Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease)

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12 pages, 1067 KiB

Open AccessArticle

Vitamin D-Binding Protein and the Free Hormone Hypothesis for Vitamin D in Bio-Naïve Patients with Psoriasis

by Maria Siekkeri Vandikas, Kerstin Landin-Wilhelmsen, Martin Gillstedt and Amra Osmancevic

Int. J. Mol. Sci. 2022, 23(3), 1302; https://doi.org/10.3390/ijms23031302 - 24 Jan 2022

Cited by 5 | Viewed by 2602

Abstract

High levels of vitamin D-binding protein (DBP) have been reported in patients with psoriasis and the possibility of DBP as a marker of inflammation has been discussed. Furthermore, high DBP levels might negatively affect free 25(OH)D concentrations. According to the free hormone hypothesis, [...] Read more.

High levels of vitamin D-binding protein (DBP) have been reported in patients with psoriasis and the possibility of DBP as a marker of inflammation has been discussed. Furthermore, high DBP levels might negatively affect free 25(OH)D concentrations. According to the free hormone hypothesis, only the free fraction of a steroid hormone is capable of exerting biological action. Thus, free 25(OH)D level could be a better biomarker of vitamin D status than total 25(OH)D level. The objectives of this study were to identify the strongest determinants for DBP levels and to test the free hormone hypothesis for vitamin D in psoriasis. Additionally, we also aimed to investigate correlations between directly measured free 25(OH)D levels in serum and psoriasis disease severity compared to total 25(OH)D levels. This was a retrospective cross-sectional study including 40 bio-naïve patients with mild to severe plaque psoriasis. Psoriasis disease severity was evaluated using high sensitivity C-reactive protein (hsCRP), Psoriasis Area Severity Index (PASI) and visual analogue scale (VAS). Vitamin D metabolites including directly measured free 25(OH)D and serum DBP levels were measured. DBP levels were higher in patients with self-reported arthropathy than those without irrespective of confounding factors like sex, age and body weight. Total and free 25(OH)D levels correlated well (ρ = 0.77, p < 0.0001) and both were inversely correlated to intact parathyroid hormone (iPTH) (ρ = −0.33, p = 0.038 for total 25(OH)D and ρ = −0.40, p = 0.010 for free 25(OH)D). Only total 25(OH)D correlated to serum calcium levels (ρ = 0.32, p = 0.047). No correlations between any of the vitamin D metabolites and psoriasis disease severity were observed. In conclusion, DBP might be a new inflammatory biomarker in psoriasis, especially in psoriatic arthritis. Total 25(OH)D was a reliable measure for vitamin D status in this psoriasis cohort. However, evaluation of free 25(OH)D in patients with psoriatic disease and multiple co-morbidities and/or ongoing biologic treatment should be considered. Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease)

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14 pages, 3530 KiB

Open AccessArticle

Inflammation- and Gut-Homing Macrophages, Engineered to De Novo Overexpress Active Vitamin D, Promoted the Regenerative Function of Intestinal Stem Cells

by Yi Xu, David J. Baylink, Huynh Cao, Jeffrey Xiao, Maisa I. Abdalla, Samiksha Wasnik and Xiaolei Tang

Int. J. Mol. Sci. 2021, 22(17), 9516; https://doi.org/10.3390/ijms22179516 - 01 Sep 2021

Cited by 10 | Viewed by 2633

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Available drugs aim to suppress gut inflammation. These drugs have significantly delayed disease progression and improved patients’ quality of life. However, the disease continues to progress, underscoring the need to develop [...] Read more.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Available drugs aim to suppress gut inflammation. These drugs have significantly delayed disease progression and improved patients’ quality of life. However, the disease continues to progress, underscoring the need to develop novel therapies. Aside from chronic gut inflammation, IBD patients also experience a leaky gut problem due to damage to the intestinal epithelial layer. In this regard, epithelial regeneration and repair are mediated by intestinal stem cells. However, no therapies are available to directly enhance the intestinal stem cells’ regenerative and repair function. Recently, it was shown that active vitamin D, i.e., 1,25-dihydroxyvitamin D or 1,25(OH)₂D, was necessary to maintain Lgr5⁺ intestinal stem cells, actively cycling under physiological conditions. In this study, we used two strategies to investigate the role of 1,25(OH)₂D in intestinal stem cells’ regenerative function. First, to avoid the side effects of systemic high 1,25(OH)₂D conditions, we used our recently developed novel strategy to deliver locally high 1,25(OH)₂D concentrations specifically to inflamed intestines. Second, because of the Lgr5⁺ intestinal stem cells’ active cycling status, we used a pulse-and-chase strategy via 5-bromo-2′-deoxyuridine (BrdU) labeling to trace the Lgr5⁺ stem cells through the whole epithelial regeneration process. Our data showed that locally high 1,25(OH)₂D concentrations enhanced intestinal stem cell migration. Additionally, the migrated cells differentiated into mature epithelial cells. Our data, therefore, suggest that local delivery of high 1,25(OH)₂D concentrations is a promising strategy to augment intestinal epithelial repair in IBD patients. Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease)

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Review

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26 pages, 1386 KiB

Open AccessReview

The Diabetic Cardiorenal Nexus

by John A. D’Elia, George P. Bayliss and Larry A. Weinrauch

Int. J. Mol. Sci. 2022, 23(13), 7351; https://doi.org/10.3390/ijms23137351 - 01 Jul 2022

Cited by 6 | Viewed by 2658

Abstract

The end-stage of the clinical combination of heart failure and kidney disease has become known as cardiorenal syndrome. Adverse consequences related to diabetes, hyperlipidemia, obesity, hypertension and renal impairment on cardiovascular function, morbidity and mortality are well known. Guidelines for the treatment of [...] Read more.

The end-stage of the clinical combination of heart failure and kidney disease has become known as cardiorenal syndrome. Adverse consequences related to diabetes, hyperlipidemia, obesity, hypertension and renal impairment on cardiovascular function, morbidity and mortality are well known. Guidelines for the treatment of these risk factors have led to the improved prognosis of patients with coronary artery disease and reduced ejection fraction. Heart failure hospital admissions and readmission often occur, however, in the presence of metabolic, renal dysfunction and relatively preserved systolic function. In this domain, few advances have been described. Diabetes, kidney and cardiac dysfunction act synergistically to magnify healthcare costs. Current therapy relies on improving hemodynamic factors destructive to both the heart and kidney. We consider that additional hemodynamic solutions may be limited without the use of animal models focusing on the cardiomyocyte, nephron and extracellular matrices. We review herein potential common pathophysiologic targets for treatment to prevent and ameliorate this syndrome. Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease)

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58 pages, 1999 KiB

Open AccessReview

Vitamin D and Ocular Diseases: A Systematic Review

by Hei-Nga Chan, Xiu-Juan Zhang, Xiang-Tian Ling, Christine Huyen-Trang Bui, Yu-Meng Wang, Patrick Ip, Wai-Kit Chu, Li-Jia Chen, Clement C. Tham, Jason C. Yam and Chi-Pui Pang

Int. J. Mol. Sci. 2022, 23(8), 4226; https://doi.org/10.3390/ijms23084226 - 11 Apr 2022

Cited by 27 | Viewed by 9244

Abstract

The contributory roles of vitamin D in ocular and visual health have long been discussed, with numerous studies pointing to the adverse effects of vitamin D deficiency. In this paper, we provide a systematic review of recent findings on the association between vitamin [...] Read more.

The contributory roles of vitamin D in ocular and visual health have long been discussed, with numerous studies pointing to the adverse effects of vitamin D deficiency. In this paper, we provide a systematic review of recent findings on the association between vitamin D and different ocular diseases, including myopia, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), dry eye syndrome (DES), thyroid eye disease (TED), uveitis, retinoblastoma (RB), cataract, and others, from epidemiological, clinical and basic studies, and briefly discuss vitamin D metabolism in the eye. We searched two research databases for articles examining the association between vitamin D deficiency and different ocular diseases. One hundred and sixty-two studies were found. There is evidence on the association between vitamin D and myopia, AMD, DR, and DES. Overall, 17 out of 27 studies reported an association between vitamin D and AMD, while 48 out of 54 studies reported that vitamin D was associated with DR, and 25 out of 27 studies reported an association between vitamin D and DES. However, the available evidence for the association with other ocular diseases, such as glaucoma, TED, and RB, remains limited. Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease)

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12 pages, 711 KiB

Open AccessReview

Impact of Vitamin D in Prophylaxis and Treatment in Tuberculosis Patients

by Roberta Papagni, Carmen Pellegrino, Francesco Di Gennaro, Giulia Patti, Aurelia Ricciardi, Roberta Novara, Sergio Cotugno, Maria Musso, Giacomo Guido, Luigi Ronga, Stefania Stolfa, Davide Fiore Bavaro, Federica Romanelli, Valentina Totaro, Rossana Lattanzio, Giuseppina De Iaco, Fabrizio Palmieri, Annalisa Saracino and Gina Gualano

Int. J. Mol. Sci. 2022, 23(7), 3860; https://doi.org/10.3390/ijms23073860 - 31 Mar 2022

Cited by 12 | Viewed by 4751

Abstract

Vitamin D plays a crucial role in many infectious diseases, such as tuberculosis (TB), that remains one of the world’s top infectious killers with 1.5 million deaths from TB in 2021. Vitamin D suppresses the replication of Mycobacterium tuberculosis in vitro and showed [...] Read more.

Vitamin D plays a crucial role in many infectious diseases, such as tuberculosis (TB), that remains one of the world’s top infectious killers with 1.5 million deaths from TB in 2021. Vitamin D suppresses the replication of Mycobacterium tuberculosis in vitro and showed a promising role in TB management as a result of its connection with oxidative balance. Our review encourages the possible in vivo benefit of a joint administration with other vitamins, such as vitamin A, which share a known antimycobacterial action with vitamin D. However, considering the low incidence of side effects even at high dosages and its low cost, it would be advisable to assess vitamin D level both in patients with active TB and high-risk groups and administer it, at least to reach sufficiency levels. Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease)

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17 pages, 3227 KiB

Open AccessReview

The Role of Vitamin D in Diabetic Nephropathy: A Translational Approach

by Charlotte Delrue, Reinhart Speeckaert, Joris R. Delanghe and Marijn M. Speeckaert

Int. J. Mol. Sci. 2022, 23(2), 807; https://doi.org/10.3390/ijms23020807 - 12 Jan 2022

Cited by 13 | Viewed by 3251

Abstract

According to several animal and human studies, vitamin D appears to play a significant role in the development of diabetic nephropathy. However, the possible renoprotective effect of vitamin D and its influence on the reversal of already existing renal damage remains doubtful. At [...] Read more.

According to several animal and human studies, vitamin D appears to play a significant role in the development of diabetic nephropathy. However, the possible renoprotective effect of vitamin D and its influence on the reversal of already existing renal damage remains doubtful. At this moment, there are a few hypotheses concerning the underlying molecular and genetic mechanisms including the link between vitamin D and inflammation, oxidative stress, and extracellular matrix accumulation. The present review aims to investigate the potential role of vitamin D in the development of diabetic kidney disease from a translational approach. Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease)

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