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Colon-specific regulation of vitamin D hydroxylases--a possible approach for tumor prevention.

Epidemiological data suggest a protective role of calcium and vitamin D against colorectal tumor pathogenesis. 1,25-dihydroxyvitamin D3 (1,25-D3) is a key determinant of calcium homeostasis, cell proliferation and differentiation. Calcium in the intestinal lumen functions as a growth regulator and may prevent cancer by direct reduction of colonocyte proliferation. While calcium or vitamin D can counteract proliferation by itself, they could also interact if nutritional calcium were to modulate colonic vitamin D synthesis. In this paper we demonstrate that colonic and renal vitamin D hydroxylas

Interface tissue fibroblasts from loose total hip replacement prosthesis produce receptor activator of nuclear factor-kappaB ligand, osteoprotegerin, and cathepsin K.

OBJECTIVE: The highly osteolytic interface tissue between the bone and loosening total hip prosthesis is characterized by low pH, formation of foreign body giant cells, osteoclasts, and production of receptor activator of nuclear factor-kappaB (RANKL) and cathepsin K. We hypothesized that fibroblasts in the interface tissue may form a source for RANKL production. METHODS: Primary interface tissue fibroblasts, fibrous joint capsule fibroblasts, and trabecular bone osteoblasts were stimulated with tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), IL-6, IL-11, or 1alpha,25-(

[Genetic background of osteoporosis].

Osteoporosis is characterized by a decrease in bone mass as well as a deterioration of the bone architecture resulting in an increased risk of fracture. The disease is multifactorial, and it depends on environmental and genetic factors. Twin studies have shown that genetic factors account for 60-80% of the variance in bone mineral density, the best predictor of the risk of osteoporosis. There are different approaches to identify these genetic factors. Linkage studies in human and experimental animals have defined multiple loci that regulate bone mass but most of the genes responsible for this

Dental follicle cell-conditioned medium enhances the formation of osteoclast-like multinucleated cells.

An influx of mononuclear cells and the subsequent increase of osteoclasts around tooth germs suggests that the dental follicle (DF) regulates or influences bone resorption required for tooth eruption. In order to study the effects of DF cell products on osteoclast formation during tooth eruption, a conditioned medium (CM) was created in which DF cells were added to mouse bone marrow cultures. Tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like multinucleated cells were formed in the presence of 10 nM 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The CM, dose-dependently, stimulated t

A beneficial aspect of a CB1 cannabinoid receptor antagonist: SR141716A is a potent inhibitor of macrophage infection by the intracellular pathogen Brucella suis.

The psychoactive component of marijuana, delta9-tetrahydrocannabinol (THC) suppresses different functions of immunocytes, including the antimicrobicidal activity of macrophages. The triggering of cannabinoid receptors of CB1 and CB2 subtypes present on leukocytes may account for these effects. We investigated the influence of specific CB1 or CB2 receptor antagonists (SR141716A and SR144528, respectively) and nonselective CB1/CB2 cannabinoid receptor agonists (CP55,940 or WIN 55212-2) on macrophage infection by Brucella suis, an intracellular gram-negative bacteria. None of the compounds tested

Clobetasol propionate followed by calcipotriol is superior to calcipotriol alone in topical treatment of psoriasis.

BACKGROUND: Although potent, topical corticosteroids offer effective and rapid healing of psoriatic lesions. Their long term use is limited because of the risk of side effects. Calcipotriol is safe for long-term treatment, but its initial efficacy is lower than with topical corticosteroids. OBJECTIVES: To investigate whether 2 weeks of treatment with clobetasol propionate 0.05% ointment bd followed by 4 weeks of treatment with calcipotriol 50 microg/g bd would offer therapeutic advantages over 6 weeks of continuous treatment with calcipotriol. METHODS: Forty-nine patients with moderate to se

Воздействие витамина D на герпесвирусные инфекции.

Помимо своей классической роли в регулировании метаболизма кальция и фосфата, витамин D также оказывает значительное влияние на модуляцию иммунитета. Витамин D регулирует иммунную реакцию, переходя от воспламенительного состояния к более толерогенному one путем увеличения выброса антивоспалительных цитокинов при одновременном ослаблении регулирования проинфламаторных цитокинов. Таким образом, низкий уровень витамина D связан с повышенным риском возникновения аутоиммунных заболеваний, таких, как множественный склероз и тип 1 диабет. Кроме того, этот прохормон также способствует высвобождению хо

Совпадение в полном тексте источника
… Vitamin D enhances the release of antimicrobial peptides. ( A ) Viral recognition enhances CYP27B1 enzyme activity, which converts 25(OH)D to 1,25(OH)D or calcitriol. … Vitamin D and Adaptative Immunity Regarding adaptative immunity, calcitriol secreted by monocytes and macrophages enhances the shift of the immune system from a proinflammatory to a tolerogenic state. …

Exploring the interaction between vitamin D pathway gene polymorphisms, vitamin D status, and depression: A population-based study.

BACKGROUND: The association between vitamin D and depression is controversial, mainly because of genetic differences and confounding factors. OBJECTIVE: To evaluate the association between vitamin D and depressive symptoms, considering the influence of genetic variations, skin color, and lifestyle. METHODS: This population-based cross-sectional study was conducted during the COVID-19 pandemic. Depressive symptoms were assessed using the Patient Health Questionnaire-9. Vitamin D deficiency was defined as levels of <20 ng/mL in healthy individuals or <30 ng/mL in at-risk groups. A genetic risk

Association between Polymorphisms in Vitamin D Pathway-Related Genes, Vitamin D Status, Muscle Mass and Function: A Systematic Review.

An association between vitamin D level and muscle-related traits has been frequently reported. Vitamin D level is dependent on various factors such as sunlight exposure and nutrition. But also on genetic factors. We, therefore, hypothesize that single nucleotide polymorphisms (SNPs) within the vitamin D pathway-related genes could contribute to muscle mass and function via an impact on vitamin D level. However, the integration of studies investigating these issues is still missing. Therefore, this review aimed to systematically identify and summarize the available evidence on the association b

Differential Involvement of Programmed Cell Death Ligands in Skin Immune Responses.

PD-1 is an immunoregulatory receptor that can bind PD-L1 or PD-L2 expressed on stimulated antigen-presenting cells. In this study, isolated antigen-presenting cells (macrophages and dendritic cells) were cultured with IFN-γ, IL-4, or IL-17A, and the expression of PD-L1 and PD-L2 was compared by flow cytometry. Strong upregulation of PD-L1 expression was observed on IFN-γ stimulation of both antigen-presenting cells as well as in response to IL-17A stimulation of macrophages compared with the expression in unstimulated controls. In contrast, only stimulation with IL-4 could upregulate PD-L2 exp

Lessons Learned from Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets Patients on Vitamin D Functions.

We summarize here lessons learned from studies on skeletal and extra-skeletal functions of vitamin D in hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) patients with a mutant, nonfunctioning vitamin D receptor (VDR). During childhood, HVDRR patients are dependent on intestinal VDR, demonstrate low intestinal fraction calcium absorption, and have a bone calcium accretion rate that leads to hypocalcemia and rickets. After puberty, there is recovery in intestinal calcium absorption and in bone calcium accretion and structure. HVDRR monocytes and lymphocytes show impairment in the exp

Immunohistochemical expression of vitamin D receptor and forkhead box P3 in classic Hodgkin lymphoma: correlation with clinical and pathologic findings.

BACKGROUND: Expression of forkhead box P3 (FOXP3), a key regulator of T-cell function, in the tumor immune microenvironment is related to survival in classic Hodgkin lymphoma (CHL). Vitamin D receptor (VDR), a transcription factor agonists have been shown to induce FOXP3 expression in T-cells and enhance recruitment of these cells to the inflammatory sites. VDR expression is CHL has been described. However, there is no data on expression of VDR in context of quantity of FOXP3 positive cells in CHL. METHODS: We examined and correlated immunohistochemical expression of VDR and FOXP3 along with

A Lipid-Based Nanocarrier Containing Active Vitamin D3 Ameliorates NASH in Mice via Direct and Intestine-Mediated Effects on Liver Inflammation.

The gut-liver axis may be involved in non-alcoholic steatohepatitis (NASH) progression. Pathogen-associated molecular patterns leak through the intestinal barrier to the liver via the portal vein to contribute to NASH development. Active vitamin D3 (1,25(OH)2D3) is a potential therapeutic agent to enhance the intestinal barrier. Active vitamin D3 also suppresses inflammation and fibrosis in the liver. However, the adverse effects of active vitamin D3 such as hypercalcemia limit its clinical use. We created a nano-structured lipid carrier (NLC) containing active vitamin D3 to deliver active vit

Vitamin D receptor targets hepatocyte nuclear factor 4α and mediates protective effects of vitamin D in nonalcoholic fatty liver disease.

Epidemiological studies have suggested a link between vitamin D deficiency and increased risk for nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanisms have remained unclear. Here, using both clinical samples and experimental rodent models along with several biochemical approaches, we explored the specific effects and mechanisms of vitamin D deficiency in NAFLD pathology. Serum vitamin D levels were significantly lower in individuals with NAFLD and in high-fat diet (HFD)-fed mice than in healthy controls and chow-fed mice, respectively. Vitamin D supplementation ameliora

Clinical burden and healthcare resource utilization among patients with chronic hypoparathyroidism, overall and by adequately vs not adequately controlled disease: a multi-country chart review.

Aims: To assess the real-world clinical burden and healthcare resource utilization (HRU) among patients with chronic hypoparathyroidism, overall and by adequately controlled (AC) vs not adequately controlled (NAC) disease, informed by guideline-recommended clinical management targets, including biochemistry and symptoms. Materials and methods: In this retrospective online chart review, endocrinologists in the US, Canada, the UK, France, Germany, Italy, and Spain were randomly selected to review the medical charts of adult patients with chronic hypoparathyroidism receiving calcium and activated

The vitamin D receptor gene as a determinant of survival in pancreatic cancer patients: Genomic analysis and experimental validation.

PURPOSE: Advanced pancreatic cancer is a highly refractory disease almost always associated with survival of little more than a year. New interventions based on novel targets are needed. We aim to identify new genetic determinants of overall survival (OS) in patients after treatment with gemcitabine using genome-wide screens of germline DNA. We aim also to support these findings with in vitro functional analysis. PATIENTS AND METHODS: Genome-wide screens of germline DNA in two independent cohorts of pancreatic cancer patients (from the Cancer and Leukemia Group B (CALGB) 80303 and the Mayo Cl

DC-SIGN and VDR polymorphisms are associated with chronic form of paracoccidioidomycosis with oral manifestations.

Paracoccidioidomycosis (PCM) is a granulomatous disease caused by fungi of the species complex of the Paracoccidioides genus. One of the main clinical manifestations of PCM is the presence of oral lesions with the presence of epithelioid granulomas. In this work, we aimed to evaluate the frequency of SNPs in the TNF-α, JAK1, VDR, DC-SIGN and FcγRIIa genes in patients with chronic PCM and verify possible association of these SNPs with the organisation pattern of the granulomas in the oral lesions. A total of 66 samples of DNA were obtained from oral lesions biopsies and 106 DNA samples were obt

Oral PSORI-CM01, a Chinese herbal formula, plus topical sequential therapy for moderate-to-severe psoriasis vulgaris: pilot study for a double-blind, randomized, placebo-controlled trial.

BACKGROUND: To provide evidence that the Chinese herbal medicine (CHM) PSORI-CM01 combined with Western medicine reduces the relapse rate of psoriasis vulgaris (PV), we plan to conduct a large-scale randomized control trial (RCT). In order to improve and perfect the RCT, this pilot study was designed to determine the feasibility and the potential of a modified protocol for the full-scale RCT. METHODS: Eligible patients with psoriasis vulgaris (PV) were enrolled into a randomized comparison in which all subjects received topical sequential therapy and PSORI-CM01 or placebo for 12 weeks. The pr

1,25-Dihydroxyvitamin D3 prevents toluene diisocyanate-induced airway epithelial barrier disruption.

The loss of airway epithelial integrity contributes significantly to asthma pathogenesis. Evidence suggests that vitamin D plays an important role in the prevention and treatment of asthma. However, its role in airway epithelial barrier function remains uncertain. We have previously demonstrated impaired epithelial junctions in a model of toluene diisocyanate (TDI)-induced asthma. In the present study, we hypothesized that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] may prevent TDI-induced epithelial barrier disruption. Male BALB/c mice were dermally sensitized and then challenged with TDI. The mic

Renal expression of FGF23 and peripheral resistance to elevated FGF23 in rodent models of polycystic kidney disease.

Fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis and is linked to cardiovascular disease and all-cause mortality in chronic kidney disease. FGF23 rises in patients with CKD stages 2-3, but in patients with autosomal dominant polycystic kidney disease, the increase of FGF23 precedes the first measurable decline in renal function. The mechanisms governing FGF23 production and effects in kidney disease are largely unknown. Here we studied the relation between FGF23 and mineral homeostasis in two animal models of PKD. Plasma FGF23 levels were increased 10-fold in 4-week-old cy/+