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1.
Anticancer Res ; 40(1): 551-556, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892611

RESUMO

BACKGROUND/AIM: To investigate the effects of vitamin D3 supplementation on gut microbiota. PATIENTS AND METHODS: Twenty adults with vitamin D insufficiency/deficiency [25(OH)D <30 ng/ml] were enrolled and given 600, 4,000 or 10,000 IUs/day of oral vitamin D3 Stool samples were collected at baseline and 8 weeks for identifying gut microbiota using 16S rRNA gene amplification and sequencing. RESULTS: Baseline serum 25(OH)D was associated with increased relative abundance of Akkermansia and decreased relative abundance of Porphyromonas (p<0.05). After the intervention, we observed a dose-dependent increase in relative abundance of Bacteroides with a significant difference between the 600 IUs and the 10,000 IUs groups (p=0.027), and Parabacteroides with a significant difference between the 600 IUs and the 4,000 IUs groups (p=0.039). CONCLUSION: Increased serum 25(OH)D was associated with increased beneficial bacteria and decreased pathogenic bacteria. A dose-dependent increase in bacteria associated with decreased inflammatory bowel disease activity was observed after vitamin D3 supplementation.


Assuntos
Colecalciferol/administração & dosagem , Colecalciferol/farmacologia , Suplementos Nutricionais , Microbioma Gastrointestinal/efeitos dos fármacos , Administração Oral , Adulto , Bactérias/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos
2.
Chem Biol Interact ; 315: 108865, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31628941

RESUMO

Treatment of breast cancer by paclitaxel (PAX) often encounters therapeutic failure most likely caused by innate/acquired resistance. Cancer stem cells (CSCs) and multidrug resistance complex (MDR-1 or P-glycoprotein) overexpression are main mechanisms implicated in chemoresistance. Increased aldehyde dehrogenase-1 (ALDH-1) was previously correlated with the stemness features of CSCs and hence is used as a marker for identification and CSCs targeting. The present study, therefore, aimed at investigating the effect of both curcumin (CUR) and vitamin D3 (D3) on MDR-1 and ALDH-1 expression and consequently the resistance to PAX both in vitro and in vivo. CUR was isolated from Turmeric rhizomes and identified using UPLC-ESI-MS/MS. For in vitro studies, the antiproliferative effect of PAX, CUR, 1,25(OH)2D3 (the active form of D3, also known as calcitriol) was determined, each alone and combined (PAX+CUR, PAX+1,25(OH)2D3, and PAX+CUR+1,25(OH)2D3) on MCF-7 breast cancer cells. Ehrlich ascites carcinoma solid tumor animal model was also used for in vivo studies. Combining CUR and/or 1,25(OH)2D3 to PAX showed synergistic cytotoxic interaction on MCF-7 cells. The apoptotic potential was also enhanced, as evidenced by a significant increase in caspase-7 and -9 as well as the pro-apoptotic Bax whereas a decrease in Bcl-2 levels was reported. Combining CUR and 1,25(OH)2D3 to PAX caused a downregulation in both MDR-1 and ALDH-1 gene expression in MCF-7 besides a decrease in their protein levels. In vivo, the triple therapy group (PAX+CUR+D3) showed the least tumor size. It also showed the lowest levels of MDR-1 and ALDH-1. PAX alone, however, showed increased levels of MDR-1 and ALDH-1 compared to control. Overall, the present study showed that PAX, as a monotherapy, demonstrated acquired resistance possibly by increasing MDR-1 expression and enriching CSCs population, as evidenced by increased ALDH-1. However, using CUR and D3 enhanced tumor response to PAX.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Neoplasias da Mama/tratamento farmacológico , Colecalciferol/farmacologia , Curcumina/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Paclitaxel/farmacologia , Retinal Desidrogenase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Camundongos , Receptores de Calcitriol/metabolismo
3.
Ecotoxicol Environ Saf ; 188: 109905, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31706245

RESUMO

Cooking oil fumes-derived PM2.5 (COFs-derived PM2.5) is the main source of indoor pollution. Exposure to COFs-derived PM2.5 can cause oxidative stress and affect angiogenesis. Here we investigated the roles of vitamin D3 (VD3) in protecting tubule formation injury induced by COFs-derived PM2.5, and the roles of ROS/NLRP3/VEGF signaling pathway in the effects. Human umbilical vein endothelial cells (HUVECs) were exposed to 0 (1‰ DMSO), 1000 nmol/l VD3, 100 µg/ml PM2.5, and 1000 nmol/l VD3 + 100 µg/ml PM2.5, respectively. Cell viability and tube formation, as well as protein and mRNA levels were measured. The results showed that exposure of COFs-derived PM2.5 dose-and time-dependently reduced the viability of HUVECs, increased the levels of mitochondrial and intracellular ROS, and changed the mitochondrial membrane potential level. While co-incubation with VD3 rescued these adverse effects. Both Western blot and real-time PCR (RT-PCR) showed that the expressions of NLRP3, caspase-1, Interleukin (IL)-1ß, and IL-18 in COFs-derived PM2.5 exposure group increased significantly, which could be effectively decreased by co-incubation with VD3. COFs-derived PM2.5 exposure could also reduce the expression of VEGF, while co-incubating HUVECs with VD3 evidently up-regulated the protein level of VEGF in HUVECs. In addition, COFs-derived PM2.5 could also inhibit the tube formation of HUVECs in vitro, which could be effectively rescued by the co-incubation of VD3. Our study proved that COFs-derived PM2.5 could damage the tubule formation of HUVECs in vitro, which could be effectively rescue by co-incubation with VD3, in which processes the ROS/NLRP3/VEGF signaling pathway played a crucial role. It provides a new theoretical basis for further study on the toxicity of PM2.5 to umbilical cord blood vessels.


Assuntos
Colecalciferol/farmacologia , Culinária , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Material Particulado/toxicidade , Veias Umbilicais/citologia , Poluição do Ar em Ambientes Fechados/efeitos adversos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Veias Umbilicais/efeitos dos fármacos , Veias Umbilicais/crescimento & desenvolvimento , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
4.
Nutrients ; 11(7)2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31319554

RESUMO

In view of continuing reports of high prevalence of severe vitamin D deficiency and low rate of infant vitamin D supplementation, an alternative strategy for prevention of vitamin D deficiency in infants warrants further study. The aim of this randomized controlled trial among 95 exclusively breastfeeding mother-infant pairs with high prevalence of vitamin D deficiency was to compare the effect of six-month post-partum vitamin D3 maternal supplementation of 6000 IU/day alone with maternal supplementation of 600 IU/day plus infant supplementation of 400 IU/day on the vitamin D status of breastfeeding infants in Doha, Qatar. Serum calcium, parathyroid hormone, maternal urine calcium/creatinine ratio and breast milk vitamin D content were measured. At baseline, the mean serum 25-hydroxyvitamin D (25(OH)D) of mothers on 6000 IU and 600 IU (35.1 vs. 35.7 nmol/L) and in their infants (31.9 vs. 29.6) respectively were low but similar. At the end of the six month supplementation, mothers on 6000 IU achieved higher serum 25(OH)D mean ± SD of 98 ± 35 nmol/L than 52 ± 20 nmol/L in mothers on 600 IU (p < 0.0001). Of mothers on 6000 IU, 96% achieved adequate serum 25(OH)D (≥50 nmol/L) compared with 52%in mothers on 600 IU (p < 0.0001). Infants of mothers on 600 IU and also supplemented with 400 IU vitamin D3 had slightly higher serum 25(OH)D than infants of mothers on 6000 IU alone (109 vs. 92 nmol/L, p = 0.03); however, similar percentage of infants in both groups achieved adequate serum 25(OH)D ≥50 nmol/L (91% vs. 89%, p = 0.75). Mothers on 6000 IU vitamin D3/day also had higher human milk vitamin D content. Safety measurements, including serum calcium and urine calcium/creatinine ratios in the mother and serum calcium levels in the infants were similar in both groups. Maternal 6000 IU/day vitamin D3 supplementation alone safely optimizes maternal vitamin D status, improves milk vitamin D to maintain adequate infant serum 25(OH)D. It thus provides an alternative option to prevent the burden of vitamin D deficiency in exclusively breastfeeding infants in high-risk populations and warrants further study of the effective dose.


Assuntos
Aleitamento Materno , Colecalciferol/administração & dosagem , Colecalciferol/farmacologia , Suplementos Nutricionais , Fenômenos Fisiológicos da Nutrição do Lactente , Fenômenos Fisiológicos da Nutrição Pré-Natal , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Prevalência , Catar , Fatores de Risco , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/prevenção & controle
5.
J Steroid Biochem Mol Biol ; 194: 105435, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31352023

RESUMO

Factors that can modify the bioavailability of orally administered vitamin D are not yet widely known. Ergosterol is a common fungal sterol found in food which has a chemical structure comparable to that of vitamin D. This study aimed to investigate the effect of ergosterol on vitamin D metabolism. Therefore, 36 male wild type-mice were randomly subdivided into three groups (n = 12) and received a diet containing 25 µg vitamin D3 and either 0 mg (control), 2 mg or 7 mg ergosterol per kg diet for 6 weeks. To elucidate the impact of ergosterol on hepatic hydroxylation of vitamin D, human hepatoma cells (HepG2) were treated with different concentrations of ergosterol. Concentrations of vitamin D3 and 25-hydroxyvitamin D3 (25(OH)D3) in cells, livers and kidneys of mice and additionally 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) in serum were quantified by LC-MS/MS. The concentration of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in serum was analyzed by commercially-available enzyme immuno assay. The concentrations of cholesterol and triglycerides were analyzed in livers of mice by photometric assays. Analyses revealed that mice receiving 7 mg/kg ergosterol with their diet had 1.3-, 1.7- and 1.5-times higher concentrations of vitamin D3 in serum, liver and kidney, respectively, than control mice (P < 0.05), whereas no significant effects were observed in mice fed 2 mg/kg ergosterol. The hydroxylation of vitamin D remained unaffected by dietary ergosterol, since the concentration of 25-hydroxyvitamin D3 in serum and tissues and the concentrations of 1,25(OH)2D3 and 24,25(OH)2D3 in serum were not different between the three groups of mice. The lipid concentrations in liver were also not affected by dietary ergosterol. Data from the cell culture studies showed that ergosterol did not influence the conversion of vitamin D3 to 25(OH)D3. To conclude, ergosterol appears to be a modulator of vitamin D3 concentrations in the body of mice, without modulating the hydroxylation of vitamin D3 in liver.


Assuntos
Colecalciferol/farmacologia , Ergosterol/farmacologia , Vitaminas/farmacologia , 24,25-Di-Hidroxivitamina D 3/sangue , 24,25-Di-Hidroxivitamina D 3/metabolismo , Animais , Calcifediol/sangue , Calcifediol/metabolismo , Colecalciferol/sangue , Colecalciferol/farmacocinética , Células Hep G2 , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Vitaminas/sangue , Vitaminas/farmacocinética
6.
Nutrients ; 11(8)2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31357443

RESUMO

The purpose of this study was to explore the antidepressant-like effects of vitamin D3 at different doses (1.0, 2.5, and 5.0 mg/kg sc) on a model of depression produced by chronic unpredictable mild stress (CUMS) for 28 days in long-term (3 months) ovariectomized (OVX) adult rats. Sucrose preference (SPT), forced swimming (FST) and open-field (OFT) tests were conducted to examine the depression-like state. Serum corticosterone/adrenocorticotrophic hormone (ACTH) levels and hippocampal brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3/NT-4 expressions by ELISA kits and/or western blotting were determined to assess the possible mechanisms of the vitamin D3 effects on the depression-like profile in long-term OVX rats subjected to CUMS. The results showed that vitamin D3 (5.0 mg/kg), as well as fluoxetine treatment, considerably reversed the depression-like state in the SPT and FST, decreased serum corticosterone/ACTH levels, and increased BDNF and NT-3/NT-4 levels in the hippocampus of long-term OVX rats compared to OVX rats with CUMS (p < 0.05). Thus, a high dose of vitamin D3 (5.0 mg/kg sc) could improve the depression-like profile in long-term OVX adult female rats subjected to the CUMS procedure, which might be mediated by the regulation of BDNF and the NT-3/NT-4 signaling pathways in the hippocampus, as well as the corticosterone/ACTH levels of the blood serum.


Assuntos
Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/sangue , Colecalciferol/farmacologia , Depressão/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Fatores de Crescimento Neural/sangue , Neurotrofina 3/sangue , Ovariectomia , Estresse Psicológico/tratamento farmacológico , Hormônio Adrenocorticotrópico/sangue , Animais , Biomarcadores/sangue , Doença Crônica , Corticosterona/sangue , Depressão/sangue , Depressão/psicologia , Modelos Animais de Doenças , Comportamento Alimentar/efeitos dos fármacos , Feminino , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Locomoção/efeitos dos fármacos , Ratos Wistar , Estresse Psicológico/sangue , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Fatores de Tempo
7.
Vopr Pitan ; 88(2): 32-39, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31233686

RESUMO

Oxidative stress is a universal mechanism of cellular damage of hepatocytes, leading to a decrease in the detoxification function of the liver, which is especially important during oncogenesis. An early correction of these mechanisms by lipophilic essential nutrients could increase the effectiveness of antitumor treatment and prevent the development and progress of cancer. Aim to study the effect of separate and combined use of ω-3 PUFA and vitamin D3 on the intensity of free radical processes, mitochondrial swelling and cytochrome c content in the liver mitochondrial fraction of the tumor-bearing rats during the intensive growth of the tumor has been studied. Material and methods. Studies were carried out on white outbred female rats weighing 130-150 g, which were divided into 5 groups (each n=12). Guerin's carcinoma was used as a model of malignant neoplasm. Carcinoma transplantation was carried out by subcutaneous injection of 0.5 ml of a 30% suspension of cancer cells into saline in the upper thigh region of the right limb. ω-3 PUFAs (120 mg/kg of body weight, per os) and vitamin D3 (600 IU/kg of body weight, per os) were pre-administered for 28 days before the transplantation of Guerin's carcinoma and after transplantation for the entire period of tumor growth in the body (14 days). Liver mitochondrial fraction was isolated by differential centrifugation. The intensity of lipid peroxidation was judged by using spectrophotometry by the content of primary, secondary, and tertiary products in isopropanol extracts. The rate of formation of the superoxide radical was recorded in a test with nitro-blue tetrazolium, the swelling of mitochondria was assessed by a decrease in the optical density of isolated mitochondria, the content of cytochrome c in the mitochondrial and cytosolic fractions was determined by multi-wavelength visible light spectroscopy. Results and discussion. An increase in the content of primary (diene and triene conjugates), secondary (ketodienes; conjugated trienes; TBA-active products) and terminal (Schiff bases) lipid peroxidation products with a simultaneous increase in the generation of superoxide anion-radical was found in the liver mitochondrial fraction of the tumorbearing rats. With the administration of ω-3 PUFA and vitamin D3, both separately and especially when used together, a decrease in the intensity of free radical processes in liver mitochondrial fraction of tumor-bearing rats has been observed. At the same time, mitochondrial swelling decreased, this prevented the release of cytochrome c from mitochondria into cytosol. Conclusion. The administration of the complex ω-3 PUFA and vitamin D3 reduces the processes of lipid peroxidation in the mitochondrial fraction of the liver of tumor-bearing rats while simultaneously restoring the functional ability of mitochondria.


Assuntos
Colecalciferol/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Neoplasias Experimentais/metabolismo , Superóxidos/metabolismo , Animais , Citocromos c/metabolismo , Feminino , Mitocôndrias Hepáticas/patologia , Neoplasias Experimentais/patologia , Ratos
8.
Inflamm Res ; 68(10): 857-866, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31236602

RESUMO

OBJECTIVE: The probably effects of sitagliptin and vitamin D3 (VitD3) on proliferation capacity and cytokines production were investigated in type 2 diabetes mellitus (T2DM) in vitro. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with T2DM and 26 healthy controls (HCs). CFSE-labeled PBMCs stimulated with phytohamagglutinin (PHA, 5 µg/mL) in the presence/absence of sitagliptin (200 mg/mL) with/without VitD3 (10-8 M) for 4 days. The proliferation of CD4+ T helper cells and non-CD4+ cells was analyzed using flow cytometry. The supernatant levels of IFN-γ, IL-17, IL-4, TGB-ß and IL-37 were detected using ELISA. RESULTS: The proliferation of CD4+ T cells in response to PHA was higher in T2DM patients compared with HCs. The production of IFN-γ and IL-17 in PHA-stimulated cultures was higher, and the levels of IL-4 and IL-37 were lower in T2DM patients compared to HCs. The addition of sitagliptin or VitD3 to the cultures decreased the CD4+ T cells and non-CD4+ cells proliferation in patients and HCs. Sitagliptin with VitD3 was more effective in suppression of proliferation, decreasing of IL-17 and enhancing of IL-37 production. CONCLUSION: Sitagliptin plus VitD3 effectively reduces the proliferative T cells response and modulates pro-inflammatory/anti-inflammatory cytokines production.


Assuntos
Colecalciferol/farmacologia , Diabetes Mellitus Tipo 2/imunologia , Hipoglicemiantes/farmacologia , Fosfato de Sitagliptina/farmacologia , Linfócitos T/efeitos dos fármacos , Vitaminas/farmacologia , Adulto , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citocinas/imunologia , Feminino , Humanos , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia
9.
Life Sci ; 231: 116537, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31176774

RESUMO

AIMS: Renal dysfunction has been reported in individuals with Down syndrome (DS); however, the causes and mechanisms involved remain unknown. Here, we present a proposal for how the triplication of the amyloid beta precursor protein (APP) and, mainly the amyloid ß peptide 1-42 (Aß42) can favor the development of renal abnormalities in DS. We evaluated the effects of vitamin D3 (VD3) supplementation on morphofunctional aspects and the repercussions on the presence and localization of Aß42, methylenetetrahydrofolate reductase (MTHFR), caspase-3 p12, and P-glycoprotein (Pgp) in the renal tissue of DS mouse model. MAIN METHODS: Twenty female mice (14-week-old) belonging to the B6EiC3Sn-Rb(12.Ts171665Dn)2Cje/CjeDnJ lineage were divided into four experimental groups (n = 5/group): common diet; trisomy (Ts) and wild-type (Wt); and high doses VD3, Ts(VD3), and Wt(VD3). All the groups were treated for 10 weeks. At 24 weeks, the protocol experimental was interrupted. The kidney was weighed, collected, and processed for immunochemical analysis for Aß42, Caspase-3 p12, MTHFR, and Pgp proteins. All data were analyzed statistically. KEY FINDINGS: Our results showed that VD3 promoted an increase in caspase-3 p12, MTHFR, and Pgp, and consequently contributed to reduced Aß42 in the renal tissue of a mouse model of DS. Furthermore, VD3 treatment affected the plasma creatinine and urea levels and contributed to the attenuation of the dilation of Bowman's space observed in trisomic mice. SIGNIFICANCE: Finally, the results showed that VD3 may activate specific mechanisms involved in reduced Aß42 and tissue repair in the kidneys of a mouse model for Down syndrome.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Colecalciferol/farmacologia , Síndrome de Down/tratamento farmacológico , Síndrome de Down/metabolismo , Rim/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/fisiologia , Animais , Caspase 3/metabolismo , Suplementos Nutricionais , Modelos Animais de Doenças , Síndrome de Down/patologia , Feminino , Rim/metabolismo , Rim/patologia , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Camundongos , Camundongos Endogâmicos BALB C
10.
Nutrients ; 11(6)2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31167402

RESUMO

We investigated whether vitamin D receptor (VDR) polymorphisms were associated with cancer biomarkers, i.e., E-cadherin, matrix metallopeptidase 9 (MMP9), interferon ß (IFNß), soluble intercellular adhesion molecule-1 (s-ICAM-1), soluble vascular cell adhesion molecule-1 (s-VCAM-1), tumor necrosis factorα (TNFα), interleukin 6 (IL6), plasminogen activator inhibitor-1(PAI-1), and human high sensitivity C-reactive protein (hs-CRP), among breast cancer survivors who received vitamin D3 supplementation. In a single-arm non-randomized pre- and post trial, 176 breast cancer survivors who had completed treatment protocol including surgery, radio and chemotherapy were enrolled in the study and received 4000 IU of vitamin D3 daily for 12 weeks. The association between the VDR SNPs (ApaI, TaqI, FokI, BsmI and Cdx2) and response variable changes was assessed using linear regression, utilizing the "association" function in the R package "SNPassoc". We observed that women with AA and GA [codominant model (AA compared to GG) and (GA compared to GG); dominant model (AA & GA compared to GG)] genotypes of Cdx2 showed higher increase in plasma MMP9 levels compared to the GG category. In addition, carriers of BsmI bb showed greater decrease in circulating TNFα levels after vitamin D3 supplementation [recessive model (bb compared to BB & Bb]. Likewise, significant associations were identified between haplotypes of VDR polymorphisms and on-study plasma MMP9 changes. However, our results indicate that VDR genetic polymorphisms were not associated with longitudinal changes in the remaining cancer biomarkers. Overall, our findings suggest that changes in certain inflammatory biomarkers in breast cancer survivors with low plasma 25(OH)D levels, supplemented with vitamin D3, may depend on VDR SNPs and haplotypes.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/metabolismo , Colecalciferol/farmacologia , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Adulto , Antineoplásicos/uso terapêutico , Neoplasias da Mama/terapia , Colecalciferol/administração & dosagem , Feminino , Haplótipos , Humanos , Pessoa de Meia-Idade , Radioterapia
11.
Medicina (Kaunas) ; 55(6)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174403

RESUMO

Background and objectives: Vitamin D is an essential vitamin that plays a key role in maintaining physiological calcium balance, and is also a pivotal element in the formation of bone structure. Vitamin D deficiency is associated with a wide array of clinical symptoms. Vitamin and mineral deficiencies are quite common prior to and after bariatric surgery, and therefore we have evaluated the effects of two different cholecalciferol supplementation regimes on serum calcium, 25(OH) cholecalciferol, and parathyroid hormone (PTH). Materials and Methods: In this retrospective matched cohort study, two different cholecalciferol supplementation regimes were compared. Group A consisted of 50 patients who had 1000 mg calcium and 800 IU cholecalciferol. In Group B, 50 patients had 1000 mg calcium and 800 IU cholecalciferol with an additional 1 ml liquid cholecalciferol (50,000 IU) monthly. The primary outcome was the effects on blood serum levels of calcium, 25(OH) cholecalciferol, and PTH. Results: In group A and group B, there were significant increases in 25(OH) cholecalciferol, with a higher delta in favor of group B (for all three p < 0.001). A decrease was seen in PTH (p < 0.001), and no differences were measured in calcium levels in both groups. Conclusion: Our study suggests that an additional 1 ml cholecalciferol (50,000 IU) monthly can result in less biochemically 25(OH) cholecalciferol deficient patients after bariatric surgery. No effects were seen on the calcium balance. However, larger randomized clinical trials need to be done to assess the effects on clinical outcomes like bone health and fracture risk.


Assuntos
Cirurgia Bariátrica/reabilitação , Cálcio/análise , Colecalciferol/uso terapêutico , Hormônio Paratireóideo/análise , Adulto , Análise de Variância , Cirurgia Bariátrica/métodos , Cálcio/sangue , Colecalciferol/farmacologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Hormônio Paratireóideo/sangue , Projetos Piloto , Período Pós-Operatório , Estudos Retrospectivos , Vitamina D/análise , Vitamina D/sangue
12.
Ecotoxicol Environ Saf ; 179: 249-256, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31054378

RESUMO

The functional role of 1,25-vitamin D3 in cooking oil fumes (COFs)-derived PM2.5-induced cell damage is largely unexplored. The present study investigated the protective role of 1,25-vitamin D3 against cell injury by possible involvement of JAK/STAT and NF-κB signaling pathways in cardiomyocytes. Cell viability was measured using CCK-8 assay, and cell apoptosis was analyzed by flow cytometry, qRT-PCR and Western blot in cultured rat neonatal cardiomyocytes treated with 1,25-vitamin D3 and COFs-derived PM2.5. Expressions of JAK/STAT and NF-κB signaling pathway were measured by Western blot. The results suggested that treatment with COFs-derived PM2.5 significantly decreased cell viability and increased apoptosis and oxidative stress in cultured rat neonatal cardiomyocytes. 1,25-vitamin D3 pretreatment alleviated the cell injury by increasing cell viability and decreasing apoptosis in the cardiomyocytes. 1,25-vitamin D3 pretreatment also decreased the ROS level and inflammation in the cardiomyocytes. Furthermore, 1,25-vitamin D3 pretreatment alleviated COFs-derived PM2.5-evoked elevation of JAK/STAT and NF-κB signaling pathways. Our study showed that 1,25-vitamin D3 pretreatment protected cardiomyocytes from COFs-derived PM2.5-induced injury by decreasing ROS, apoptosis and inflammation level via activations of the JAK/STAT and NF-κB signaling pathways.


Assuntos
Poluentes Atmosféricos/toxicidade , Anti-Inflamatórios/farmacologia , Colecalciferol/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Material Particulado/toxicidade , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Culinária/métodos , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Ratos , Transdução de Sinais/efeitos dos fármacos
13.
Int J Mol Sci ; 20(9)2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31086078

RESUMO

Previously, we have reported that the active vitamin D metabolite, calcitriol and vitamin D3 (cholecalciferol), both remarkably inhibit hepatitis C virus production. The mechanism by which vitamin D3 exerts its effect is puzzling due to the low levels of calcitriol produced in vitamin D3-treated Huh7.5 cells. In this study, we aimed to explore the mechanism of vitamin D3 anti-hepatitis C virus effect. We show that vitamin D3 activity is not mediated by its metabolic conversion to calcitriol, but may be due to its primary metabolic product 25(OH)D3. This is inferred from the findings that 25(OH)D3 could inhibit hepatitis C virus production in our system, and that adequate concentrations needed to exert this effect are produced in Huh7.5 cells treated with vitamin D3. Using the CRISPR-Cas9 editing technology to knockout the vitamin D receptor, we found that the antiviral activity of vitamin D3 and 25(OH)D3 was not impaired in the vitamin D receptor knockout cells. This result indicates that 25(OH)D3 anti-hepatitis C virus effect is exerted by a vitamin D receptor-independent mode of action. The possibility that vitamin D3 and 25(OH)D3, being 3ß-hydroxysteroids, affect hepatitis C virus production by direct inhibition of the Hedgehog pathway in a vitamin D receptor-independent manner was ruled out. Taken together, this study proposes a novel mode of action for the anti-hepatitis C virus activity of vitamin D3 that is mediated by 25(OH)D3 in a vitamin D receptor-independent mechanism.


Assuntos
Calcifediol/farmacologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/virologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/fisiologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/virologia , Receptores de Calcitriol/metabolismo , Sistemas CRISPR-Cas/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Colecalciferol/farmacologia , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Calcitriol/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
Tuberculosis (Edinb) ; 116S: S42-S58, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31126718

RESUMO

Vitamin D3 is known to be a key component in the defense against Mycobacterium tuberculosis (Mtb) infection through the regulation of cytokine and effector molecules. Conversely, alcohol exposure has been recognized as an immune dysregulator. Macrophages were extracted from D3 deficient and sufficient diet mice and supplemented with D3 or exposed to ethanol during ex vivo infection using M. bovis BCG, as a surrogate for Mtb. Results of our study indicate that while exogenous supplementation or alcohol exposure did alter immune response, in vivo diet was the greatest determinant of cytokine and effector molecule production. Alcohol exposure was found to profoundly dysregulate primary murine macrophages, with ethanol-exposed cells generally characterized as hyper- or hyporesponsive. Exogenous D3 supplementation had a normative effect for diet deficient host, however supplementation was not sufficient to compensate for the effects of diet deficiency. Vitamin D3 sufficient diet resulted in reduced cell cytotoxicity for the majority of time points. Results provide insight into the ramifications of both the individual and combined health risks of D3 deficiency or alcohol exposure. Given the clinical relevance of D3 deficiency and alcohol use comorbidities, outcomes of this study have implications in therapeutic approaches for the treatment of tuberculosis disease.


Assuntos
Colecalciferol/farmacologia , Suplementos Nutricionais , Etanol/toxicidade , Macrófagos/efeitos dos fármacos , Mycobacterium bovis/patogenicidade , Tuberculose/microbiologia , Deficiência de Vitamina D/tratamento farmacológico , Animais , Carga Bacteriana , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Interações Hospedeiro-Patógeno , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos Endogâmicos C57BL , Mycobacterium bovis/imunologia , Mycobacterium bovis/metabolismo , Tuberculose/imunologia , Tuberculose/metabolismo , Deficiência de Vitamina D/imunologia , Deficiência de Vitamina D/metabolismo , Deficiência de Vitamina D/microbiologia
15.
Zhonghua Shao Shang Za Zhi ; 35(4): 284-291, 2019 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-31060176

RESUMO

Objective: To explore the effects of vitamin D3 on intestinal mucosal barrier of mice with severe burns. Methods: Forty-two C57BL/6C male mice aged eight to twelve weeks were divided into vitamin D3 vehicle+ sham injury group of seven mice, vitamin D3 vehicle+ burn injury group of fourteen mice, vitamin D3+ sham injury group of seven mice, and vitamin D3+ burn injury group of fourteen mice according to random number table. Mice in vitamin D3 vehicle+ sham injury group and vitamin D3 vehicle+ burn injury group were injected with vehicle of vitamin D3 at a dose of 0.1 mL intraperitoneally at 1, 24, and 48 h before burn experiment. Mice in vitamin D3+ sham injury group and vitamin D3+ burn injury group were injected with vitamin D3 at a dose of 100 ng/kg dissolved in 0.1 mL vehicle intraperitoneally at the same time points. Mice in vitamin D3 vehicle+ burn injury group and vitamin D3+ burn injury group were inflicted with 30% total body surface area full-thickness dermal scald (hereinafter referred to as burn) on the back by 98 ℃ hot water for 3 to 4 seconds. And mice in vitamin D3 vehicle+ sham injury group and vitamin D3+ sham injury were treated with 37 ℃ water on the back for 3 to 4 seconds to simulate injury. Seven mice in vitamin D3 vehicle+ sham injury group and seven mice in vitamin D3+ sham injury group at post injury hour (PIH) 24, and seven mice in vitamin D3 vehicle+ burn injury group and seven mice in vitamin D3+ burn injury group at PIH 6 and 24 were sacrificed respectively to collect mesentery lymph nodes, spleens, livers, and intestinal tissue. The mesentery lymph nodes, spleens, and livers of mice in each group were collected to observe growth of bacteria, and number of bacteria was counted. Intestinal tissue of mice in each group was collected to detect protein expressions of zonal occludin 1 (ZO-1) and occludin by immunohistochemistry staining method, distribution of ZO-1 by immunofluorescence staining method, and expression of occludin by Western blotting. Data were processed with Kruskal-Wallis H test, Nemenyi test, one-way analysis of variance, t test, and Bonferroni correction. Results: (1) At PIH 6 and 24, bacterial counts of mesentery lymph nodes, livers, and spleens of mice in vitamin D3 vehicle+ burn injury group were significantly higher than those of mice in vitamin D3 vehicle+ sham injury group (P<0.05). At PIH 6, bacterial counts of livers and spleens of mice in vitamin D3+ burn injury group were significantly lower than those of mice in vitamin D3 vehicle+ burn injury group (P<0.05). At PIH 24, bacterial counts of mesentery lymph nodes and livers of mice in vitamin D3+ burn injury group were significantly lower than those of mice in vitamin D3 vehicle+ burn injury group (P<0.05). (2) At PIH 6 and 24, expressions of ZO-1 and occludin of intestinal tissue of mice in vitamin D3 vehicle+ burn injury group were significantly lower than those of mice in vitamin D3 vehicle+ sham injury group, and expressions of ZO-1 and occludin of intestinal tissue of mice in vitamin D3+ burn injury group were close to those of mice in vitamin D3+ sham injury group. At PIH 6 and 24, expressions of ZO-1 and occludin of intestinal tissue of mice in vitamin D3+ burn injury group were significantly higher than those of mice in vitamin D3 vehicle+ burn injury group. (3) At PIH 6 and 24, compared with that of mice in vitamin D3 vehicle+ sham injury group, distribution of ZO-1 of intestinal mucosal epithelium of mice in vitamin D3 vehicle+ burn injury group was discontinuous. Distribution of ZO-1 of intestinal mucosal epithelium of mice in vitamin D3+ sham injury group was normal, and the distribution of ZO-1 of intestinal mucosal epithelium of mice in vitamin D3+ burn injury group was with good continuity. (4) At PIH 6 and 24, expressions of occludin of intestinal tissue of mice in vitamin D3 vehicle+ burn injury group were 0.720±0.003, 0.638±0.052 respectively, significantly lower than 0.918±0.003 of mice in vitamin D3 vehicle+ sham injury group (t=57.33, 5.36, P<0.05). At PIH 6 and 24, expressions of occludin of intestinal tissue of mice in vitamin D3+ burn injury group were 0.994±0.058, 1.064±0.060, close to 0.938±0.023 of mice in vitamin D3+ sham injury group (t=0.91, 1.96, P>0.05). At PIH 6 and 24, expressions of occludin of intestinal tissue of mice in vitamin D3 vehicle+ burn injury group were significantly lower than those of mice in vitamin D3+ burn injury group (t=4.75, 5.35, P<0.05). Conclusions: Intestinal bacterial translocation can occur in the early stage of severe burn. And vitamin D3 plays a protective role in the intestinal mucosal barrier post severe burn to reduce the bacterial translocation by protecting tight junction proteins of intestinal epithelium.


Assuntos
Queimaduras , Colecalciferol/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Animais , Colecalciferol/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley
16.
J Nutr Sci Vitaminol (Tokyo) ; 65(2): 113-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061279

RESUMO

Food allergy prevalence is increasing all over the world. Recent epidemiologic studies have shown the link between vitamin D3 insufficiency and food allergy occurrence. In this study, we investigated the effect of supplementation with cholecalciferol, a widely used form of vitamin D3, on food allergy using an experimental mouse model. In wild-type BALB/c mice which were sensitized and challenged with an experimental allergen, ovalbumin, a clinical symptom of food allergy, diarrhea, was significantly induced with the elevation of immunoglobulin E level and the increases of T helper 2 cytokine productions, such as interleukin-4, -5, and -13 (p<0.05), whereas no change in T helper 1 cytokine production, such as interferon-γ, was observed. It was also found that cell population of CD69+ CD4+ T cells was increased slightly in spleen and significantly in the mesenteric lymphnode with the diarrheal symptom (p<0.05). Treatment of cholecalciferol reduced the allergic diarrhea (p<0.05) with the decreasing tendency of CD69+ CD4+ T cells, suggesting that the cell population might be associated with the attenuating effect of cholecalciferol on diarrhea occurrence, although immunoglobulin E levels and cytokine productions were not significantly altered by the treatment of cholecalciferol. When given the mice anti-CD69 mAb treatment, significant improvement of allergic diarrhea symptom was observed (p<0.05), accompanying the decrease of CD69+ CD4+ T cells which suggested the contribution of these cells to the diarrhea symptom. Taken together, we suggest that administration of cholecalciferol might be useful to suppress symptomatic food allergy in association with the decrease of CD69+ CD4+ T cells.


Assuntos
Antígenos CD , Antígenos de Diferenciação de Linfócitos T , Linfócitos T CD4-Positivos , Colecalciferol/farmacologia , Hipersensibilidade Alimentar , Lectinas Tipo C , Animais , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/imunologia , Antígenos de Diferenciação de Linfócitos T/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Citocinas/análise , Citocinas/metabolismo , Diarreia/imunologia , Diarreia/metabolismo , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Lectinas Tipo C/imunologia , Lectinas Tipo C/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Linfonodos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo
17.
Microb Pathog ; 131: 15-21, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30930221

RESUMO

Staphylococcus aureus is a major pathogen of subclinical bovine mastitis that usually is chronic and recurrent, which has been related to its ability to internalize into bovine mammary epithelial cells (bMECs). Previously, we reported that short and medium fatty acids and cholecalciferol reduce S. aureus internalization into pretreated-bMECs with these molecules suggesting a role as immunomodulatory agents. Hence, we assessed the role of sodium butyrate (NaB), sodium octanoate (NaO) and cholecalciferol on S. aureus adhesin expression and its internalization into bMECs. S. aureus pre-treated 2 h with 0.5 mM or 2 mM NaB showed a reduction in internalization into bMECs (∼35% and ∼55%; respectively), which coincided with a down-regulated expression of clumping factor B (ClfB). Also, the S. aureus internalization reduction by 2 mM NaB (2 h) agreed with a down-regulated expression of sdrC. Moreover, the 2 mM NaB (24 h) pre-treatment induced bacterial internalization (∼3-fold), which was related with an up-regulation of spa, clfB and sdrC genes. Also, NaO (0.25 mM and 1 mM) only reduced S. aureus internalization when bacteria were grown 2 h with this molecule but there was no relationship with adhesin expression. In addition, cholecalciferol (50 nM) reduced bacteria internalization at similar levels (∼50%) when bacteria were grown 2 and 24 h in broth supplemented with this compound, which correlated with spa and sdrC mRNA expression down-regulated at 2 h, and fnba and clfB mRNA expression decreased at 24 h. In conclusion, our data support the fact that fatty acids and cholecalciferol regulate adhesin gene expression as well as bacteria internalization in nonprofessional phagocytic cells, which may lead to development of anti-virulence agents for control of pathogens.


Assuntos
Adesinas Bacterianas/genética , Células Epiteliais/imunologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Glândulas Mamárias Animais/imunologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Adesinas Bacterianas/efeitos dos fármacos , Animais , Proteínas de Bactérias/genética , Ácido Butírico , Caprilatos/farmacologia , Bovinos , Linhagem Celular , Colecalciferol/farmacologia , Regulação para Baixo/efeitos dos fármacos , Células Epiteliais/microbiologia , Ácidos Graxos/farmacologia , Feminino , Gentamicinas/farmacologia , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Imunomodulação , Glândulas Mamárias Animais/microbiologia , Mastite Bovina/imunologia , Mastite Bovina/microbiologia , Mastite Bovina/prevenção & controle , RNA Mensageiro/metabolismo , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/prevenção & controle , Fatores de Virulência/genética
18.
Yakugaku Zasshi ; 139(4): 497-503, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30930376

RESUMO

Tissue barriers contribute to the maintenance of homeostasis in the body, and tissue barrier dysfunction presents a risk factor for a variety of diseases. The blood-brain barrier (BBB) is a major tissue barrier acting as a static barrier and dynamic interface that plays an important role in the maintenance of central nervous system homeostasis. We show the functional characterization of the brain-to-blood efflux transport system of amyloid-ß peptide (Aß) across the BBB. We found that activated vitamin D3 may be a candidate agent for modulating the Aß clearance across the BBB. Cerebral creatine deficiency syndromes are caused by loss-of-function mutations in the creatine transporter (CRT; SLC6A8), which transports creatine at the BBB. We found that functional impairment of CRT due to a G561R mutation resulted in incomplete N-linked glycosylation due to misfolding during protein maturation, leading to impaired creatine transport activity at the BBB. To develop a delivery system for biomedicine across the tissue barrier, we established a screening system to identify cell-penetrating peptides by a combination of in vitro cell permeability screening assays and phage display technology. Using this system, we identified cyclic hepta-peptides that are able to facilitate intestinal absorption of phages in vitro and in vivo, which are promising candidates as a carrier for macromolecular biomedicines. In conclusion, these studies focusing on the dynamic interface of tissue barriers will contribute to knowledge on disease pathogenesis as well as the development of a targeted biomedicine delivery system.


Assuntos
Barreira Hematoencefálica/metabolismo , Sistemas de Liberação de Medicamentos , Descoberta de Drogas , Doença de Alzheimer/etiologia , Peptídeos beta-Amiloides/metabolismo , Animais , Encefalopatias Metabólicas Congênitas/etiologia , Encefalopatias Metabólicas Congênitas/genética , Colecalciferol/farmacologia , Creatina/deficiência , Creatina/genética , Glicosilação , Humanos , Mutação com Perda de Função , Proteínas de Membrana Transportadoras/genética , Retardo Mental Ligado ao Cromossomo X/etiologia , Retardo Mental Ligado ao Cromossomo X/genética , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/deficiência , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/genética
19.
Int Immunopharmacol ; 72: 55-61, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30959372

RESUMO

OBJECTIVE: Vitamin D3 and progesterone (P4) both belong to steroid hormones. These hormones have effects on the function of each other in different ways. The immunomodulatory activity of vitamin D3 and P4 and their role in inducing maternal tolerance for fetus have been shown in various studies. The purpose of this study was to evaluate the effect of vitamin D3 on the expression of membrane progesterone receptors (mPRs) on CD4+ T cells. MATERIALS AND METHODS: Naive CD4+ T cells were isolated from peripheral blood of 38 healthy women of childbearing age. After stimulating by anti-CD3 and anti-CD28 monoclonal antibodies (mAb), these cells were exposed to either various concentrations of vitamin D3 or no exposure at all in a culture medium at 37 °C for 3 days. In the final stage, the mean fluorescence intensity (MFI) of mPRα and mPRß were evaluated using polyclonal and monoclonal antibodies and several gating strategies on CD4+ T cells. RESULTS: Vitamin D3 significantly increased the expression of mPR α and mPR ß on the surface of CD4+ T cells (p ≤ 0.05). CONCLUSION: The present study demonstrated the potential effect of vitamin D3 on increasing the expression of P4 receptors on CD4+ T cells. This study shows a new aspect of correlation between vitamin D3 and P4 that may influence P4 performance. Therefore, our findings suggest that the appropriate level of this vitamin may affect the optimum P4 immunomodulatory activity during pregnancy.


Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Colecalciferol/farmacologia , Receptores de Progesterona/metabolismo , Vitaminas/farmacologia , Adulto , Linfócitos T CD4-Positivos/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Feminino , Humanos , Adulto Jovem
20.
BMC Res Notes ; 12(1): 216, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30961641

RESUMO

OBJECTIVE: Vitamin D receptor (VDR) activities have been noted for a number of B cell malignancies which showed varying sensitivities to vitamin D3 (1,25-dihydroxyvitamin D3, VD3, calcitriol) and its synthetic analogs. The objective of this study was to address the potential effects of VD3 and vitamin D3 analogs (VDAs) on the growth of Hodgkin's lymphoma (HL), a malignant pathology of B cell origin, in vitro. RESULTS: Immunofluorescence staining showed the expression of VDR by primary Hodgkin's (H) and Reed-Sternberg (RS)-HRS-tumor cells in HL histological sections. Western blot analyses revealed expression of VDR in the HL cell lines Hs445, HDLM2, KMH2, and L428. One-way analysis of variance (ANOVA) on data obtained from water-soluble tetrazolium 1 (WST-1) cell proliferation assay showed decreased cell growth in HDLM2 and L428, 72 h after treatment with 10 µM of either VD3 of VDAs. Western blot analyses showed that treatment of L428 cells with the VDAs (calcipotriol and EB1089) resulted in modest increases in nuclear accumulation of VDR (nuVDR) compared to either dimethyl sulfoxide (DMSO) or VD3 treatments. nuVDR for DMSO control and VD3 was comparable. These results suggest that VD3 or VDAs may affect growth of HL.


Assuntos
Calcitriol/análogos & derivados , Colecalciferol/farmacologia , Regulação Neoplásica da Expressão Gênica , Receptores de Calcitriol/genética , Vitamina D/análogos & derivados , Calcitriol/metabolismo , Calcitriol/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colecalciferol/metabolismo , Dimetil Sulfóxido/farmacologia , Doença de Hodgkin/metabolismo , Doença de Hodgkin/patologia , Humanos , Receptores de Calcitriol/agonistas , Receptores de Calcitriol/metabolismo , Vitamina D/metabolismo , Vitamina D/farmacologia
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