1,25-dihydroxyvitamin D3 （VD3）, an active form of Vitamin D, is photosynthesized in the skin of vertebrates in response to solar ultraviolet B radiation （UV-B）. VD3 deficiency can cause health problems such as imm...1,25-dihydroxyvitamin D3 （VD3）, an active form of Vitamin D, is photosynthesized in the skin of vertebrates in response to solar ultraviolet B radiation （UV-B）. VD3 deficiency can cause health problems such as immune disease, metabolic disease, and bone disorders. It has also been demonstrated that VD3 is involved in reproductive functions. Female sex hormones such as estrogen and progesterone are biosynthesized mainly in ovarian granulosa cells as the ovarian follicle develops. The functions of sex hormones include regulation of the estrus cycle and puberty as well as maintenance of pregnancy in females. In this study, we isolated granulosa cells from porcine ovaries and cultured them for experiments. To examine the effects of VD3 on ovarian granulosa cells, the mRNA and protein levels of genes were analyzed by Real-time PCR and Western blotting assay. Production of progesterone from granulosa cells was also measured by ELISA assay. As a result, transcriptional and translational regulation of progesterone biosynthesis-related genes in granulosa cells was significantly altered by VD3. Furthermore, progesterone concen- trations in porcine granulosa cell-cultured media decreased in response to VD3. These results show that VD3 was a strong regulator of sex steroid hormone production in porcine granulosa cells, suggesting that vitamin D deficiency may result in inappropriate sexual development of industrial animals and eventually economic loss.展开更多
Objective:To evaluate the development of ovarian follicles in female albino rats following vitamin D3 supplementation.Methods:Eighteen prepubertal female albino rats,aged 3-4 weeks,weighing(70.25±9.16)g,were assi...Objective:To evaluate the development of ovarian follicles in female albino rats following vitamin D3 supplementation.Methods:Eighteen prepubertal female albino rats,aged 3-4 weeks,weighing(70.25±9.16)g,were assigned to three groups(n=6 in each group).Group A was treated with 5.00 mL/kg of distilled water and served as the control group,group B was treated with 0.025 mg/kg of vitamin D3 dissolved in distilled water,and group C was treated with 0.125 mg/kg of vitamin D3 dissolved in distilled water.All treatments were administered orally,twice weekly for 28 days.Blood and ovaries were harvested under anaesthesia.Serum vitamin D3 levels were determined by using spectrophotometric method.Ovaries were processed for histology and every10th hematoxylin and eosin stained-section was selected for histomorphometry.The number of follicles at each developmental stage was estimated.Results:Both 0.025 mg/kg and 0.125 mg/kg of vitamin D3 significantly increased serum concentrations of vitamin D3 and calcium(P<0.05),but did not alter inorganic phosphorus concentration(P>0.05).The control group had fewer growing follicles(primary,secondary and antral follicles)and more non-growing follicles(primordial and atretic follicles)when compared with the vitamin D3-supplemented groups(P<0.05).Vitamin D3 at 0.025 mg/kg significantly increased antral follicles and corpora lutea counts(P<0.05).Vitamin D3 at 0.125 mg/kg significantly increased total,primordial and atretic follicles counts(P<0.05),but significantly decreased primary,secondary,antral follicles count,ovarian weight,relative ovarian weight,and ovarian surface area when compared with the control group and rats treated with 0.025 mg/kg of vitamin D3(P<0.05).Conclusions:Vitamin D3 supplementation at 0.025 mg/kg can enhance optimal ovarian follicle recruitment and development in female rats.展开更多
<span style="font-family:Verdana;"><strong>Objectives:</strong> Rheumatoid arthritis is sometimes misdiagnosed for other diseases, like psoriatic arthritis, erosive OA, viral arthritis, rea...<span style="font-family:Verdana;"><strong>Objectives:</strong> Rheumatoid arthritis is sometimes misdiagnosed for other diseases, like psoriatic arthritis, erosive OA, viral arthritis, reactive arthritis, IBD arthritis, Lyme’s disease, and palindromic rheumatism. Secondary hyperparathyroidism was not included in the differential diagnosis of RA, though it sometimes presents with joint pains and tenderness, and even arthritis. Fibromyalgia is a psychosomatic disorder characterized by chronic widespread pain and tender areas. Mimicry of some manifestations of these diseases sometimes results in misdiagnosis as RA. <strong>Methods:</strong> Two hundred patients previously diagnosed as RA from outpatient clinics in Al-Azhar Faculty of Medicine, attended as not responding to medical treatment of RA. All patients were subjected to a re-evaluation of disease activity including HAQ, and DAS 28, CDAI, and SDAI. Also, we measured serum vitamin D3, PTH, total and ionized Calcium, Phosphorus, Uric acid, ACPA, and other routine lab. All patients were exposed to various radiological imaging modalities. <strong>Results:</strong> Cases not responding to RA treatment were reevaluated and were found to have a syndrome of fibromyalgia associated with vitamin D3 deficiency and secondary hyperparathyroidism. <strong>Conclusions:</strong> Fibromyalgia/Hyperparathyroidism syndrome is an underdiagnosed disease, which results from chronic vitamin D3 deficiency. SHPT can cause bone erosions, which are mostly shaggy in appearance and distributed in the radiocarpal, radioulnar, metacarpophalangeal and distal interphalangeal joints, in contrast to that which predominate proximal IP joints of rheumatoid arthritis. Radiology of FM/HPT syndrome patients revealed a sign of spur-like excrescences in terminal finger tufts unilaterally or bilaterally, which we think is pathognomonic.</span>展开更多
<strong>Objective:</strong><span style="font-family:Verdana;"> To determine and compare the effect of vitamin D3 supplementation on modifying the disease severity in cystic fibrosis (CF) an...<strong>Objective:</strong><span style="font-family:Verdana;"> To determine and compare the effect of vitamin D3 supplementation on modifying the disease severity in cystic fibrosis (CF) and non</span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis pediatric patients.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Methods: </span></b><span style="font-family:Verdana;">A randomized clinical trial evaluating the role of oral vitamin D3 supplementation for six months, was performed in forty patients with CF and non</span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis under the age of 18 years with vitamin D deficiency or insufficiency. The primary outcome was to reach the sufficient Vitamin D level, the secondary outcome was to reevaluate bronchiectasis severity by following up the frequency, severity of pulmonary exacerbations and lung function after vitamin D3 supplementation.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Results:</span></b><b><span style="font-family:""> </span></b><span style="font-family:Verdana;">Forty patients completed the trial. The percentage of improvement of vitamin D level after vitamin D3 supplementation for six months was significantly higher in CF (88.3%) than non</span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis patients (59.82%)</span><span style="font-family:""> </span><span style="font-family:Verdana;">(P =</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.03).</span><span style="font-family:""> </span><span style="font-family:Verdana;">Additionally, moderate to severe pulmonary exacerbations significantly decreased by more than 60%, 45% (P</span><span style="font-family:""> </span><span style="font-family:Verdana;">=</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.001,</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.005) and frequent exacerbations decreased by 15%, 10% (P</span><span style="font-family:""> </span><span style="font-family:Verdana;">=</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.327, 0.490), while the forced expiratory volume in 1 (FEV1) significantly increased by 17% and 15% in non CF bronchiectasis and CF patients respectively (p</span><span style="font-family:""> </span><span style="font-family:Verdana;"><</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">0.001).</span><b><span style="font-family:Verdana;"> Conclusions: </span></b><span style="font-family:Verdana;">Vitamin D3 therapy was effective in decreasing the frequency and severity of pulmonary exacerbations and preserving lung function. Thereby, improving the disease severity even more in non</span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis than CF patients.</span>展开更多
AIM:The effects of vitamin D3 have been investigated on various tumors, including colorectal cancer (CRC). 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1), the enzyme that inactivates the active vitamin D3 metabolite 1,...AIM:The effects of vitamin D3 have been investigated on various tumors, including colorectal cancer (CRC). 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1), the enzyme that inactivates the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25-D3), is considered to be the main enzyme determining the biological halflife of 1,25-D3. During colorectal carcinogenesis, the expression and concentration of CYP24A1 increases significantly, suggesting that this phenomenon could be responsible for the proposed efficacy of 1,25-D3 in the treatment of CRC. The aim of this study was to investigate the anti-tumor effects of vitamin D3 on the human CRC cell line Caco-2 after inhibition of the cytochrome P450 component of CYP24A1 activity. METHODS:We examined the expression of CYP24A1 mRNA and the effects of 1,25-D3 on the cell line Caco-2 after inhibition of CYP24A1. Cell viability and proliferation were determined by means of sulforhodamine-B staining and bromodeoxyuridine incorporation, respectively, while cytotoxicity was estimated via the lactate dehydrogenase content of the cell culture supernatant. CYP24A1 expression was measured by realtime reverse transcription polymerase chain reaction. A number of tetralone compounds were synthesized to investigate their CP24A1 inhibitory activity. RESULTS:In response to 1,25-D3, CYP24A1 mRNA expression was enhanced significantly, in a time- and dose-dependent manner. Caco-2 cell viability and proliferation were not influenced by the administration of 1,25-D3 alone, but were markedly reduced by coadministration of 1,25-D3 and KD-35, a CYP24A1-inhibiting tetralone. Our data suggest that the mechanism of action of co-administered KD-35 and 1,25-D3 does not involve a direct cytotoxic effect, but rather the inhibition of cell proliferation. CONCLUSION:These findings demonstrate that the selective inhibition of CYP24A1 by compounds such as KD-35 may be a new approach for enhancement of the anti-tumor effect of 1,25-D3 on CRC.展开更多
A new six intraperitoneal injection insulin-mimetic vanadyl(Ⅱ) compounds [(VD3^-1)(VO^+2)(AAn^-1)](where(n=1~6);AA1=isoleucine, AA2=threonine, AA3=proline, AA4=phenylalanine, AA5=lysine and AA6=glutamine) were synthe...A new six intraperitoneal injection insulin-mimetic vanadyl(Ⅱ) compounds [(VD3^-1)(VO^+2)(AAn^-1)](where(n=1~6);AA1=isoleucine, AA2=threonine, AA3=proline, AA4=phenylalanine, AA5=lysine and AA6=glutamine) were synthesized by the chemical reactions between vitamin D3(VD3), VOSO4 and amino acids(AAn) with equal molar ratio 1∶1∶1 in neutralized media. The structures of these complexes were elucidated by spectroscopic methods like, infrared and solid reflectance spectroscopes. Magnetic moments and electronic spectra reveal square pyramid geometrical structure of the complexes. The infrared spectra assignments of these complexes revealed that the chelation towards vanadyl(Ⅳ) ions existed via deprotonation of the hydroxyl group of VD3 drug ligand and so amino acids act as bidentate ligand via N-amino and O-carboxylate groups. The anti-diabetic efficiency of these complexes were evaluated against streptozotocin induced diabetic male albino rats.展开更多
Vitamin D_3 has been found to produce therapeutic effects on obesity-associated insulin resistance and dyslipidemia through its potent anti-inflammatory activity, but the precise immunomodulatory mechanism remains poo...Vitamin D_3 has been found to produce therapeutic effects on obesity-associated insulin resistance and dyslipidemia through its potent anti-inflammatory activity, but the precise immunomodulatory mechanism remains poorly understood. In the present study we found that 1,25-dihydroxyvitamin D_3[1,25(OH)_2D_3], the biologically active form of vitamin D_3, significantly attenuated monosodium glutamate(MSG)-induced obesity and insulin resistance as indicated by body weight reduction, oral glucose tolerance improvement, and a glucose infusion rate increase as detected with hyperinsulinemiceuglycemic clamp. Moreover, 1,25(OH)_2D_3 not only restored pancreatic islet functions but also improved lipid metabolism in insulin-targeted tissues. The protective effects of 1,25(OH)_2D_3 on glycolipid metabolism were attributed to its ability to inhibit an obesity-activated inflammatory response in insulin secretory and targeted tissues, as indicated by reduced infiltration of macrophages in pancreas islets and adipose tissue while enhancing the expression of Tgf-β1 in liver tissue, which was accompanied byincreased infiltration of Treg cells in immune organs such as spleen and lymph node as well as in insulintargeted tissues such as liver, adipose, and muscle. Together, our findings suggest that 1,25(OH)_2D_3 serves as a beneficial immunomodulator for the prevention and treatment of obesity or metabolic syndrome through its anti-inflammatory effects.展开更多
Background Several studies found that vitamin D3 might alter glucose metabolism,protect kidney from injury and even proposed the mechanisms.But results from previous studies have been conflicting.The aim of this study...Background Several studies found that vitamin D3 might alter glucose metabolism,protect kidney from injury and even proposed the mechanisms.But results from previous studies have been conflicting.The aim of this study was to evaluate the efficacy and safety of vitamin D3 in patients with diabetic nephropathy.The underlying mechanism of vitamin D3 decreasing proteinuria is also discussed.Methods We conducted a search of English and Chinese articles using database of Pubmed,Embase,Sinomed,CNKI,Wanfang and clinical trial register centers,for randomized controlled trials of vitamin D3 in diabetic nephropathy patients.Two reviewers performed independently.Meta-analysis was used when studies were homogeneous enough.Results Twenty studies,including 1 497 patients with diabetic nephropathy,were involved in this systemic review.Vitamin D3-treated patients with diabetic nephropathy had a statistically significant reduction in 24-hour proteinuria （weighted mean difference-0.44,95% CI-0.54 to-0.34,Z=8.80,P 〈0.000 01） and urine albumin/creatine ratio （standardized mean difference-0.29,95% CI-0.48 to-0.10,Z=2.96,P=0.003）.But vitamin D3 supplementation did not significantly reduce blood pressure and hemoglobin A1c compared with control group.The potential mechanisms about the renal protection of vitamin D3,including the inhibition of rennin-angiotensin system,the protection of kidney from inflammation,fibrosis and the structure change of kidney are discussed.In addition,vitamin D3 did not significantly increase the incidence of adverse effects,including total adverse effects,gastrointestinal adverse effects and fluctuation of blood pressure.Conclusions Vitamin D3 can ameliorate proteinuria and protect kidney from injury in patients with diabetic nephropathy.This renoprotective effect is independent of blood pressure and glucose reduction.And it does not increase any adverse effects than control,even in combination therapy with angiotensin converting enzyme inhibitors/angiotensin receptor blockers.But due to the limited randomized controlled trials of high quality,more clinical researches should be taken in the future.展开更多
Background Allergen-specific immunotherapy can induce immune tolerance to specific allergens by regulating immune status of individuals. However, its clinical application is limited due to individual differences in ef...Background Allergen-specific immunotherapy can induce immune tolerance to specific allergens by regulating immune status of individuals. However, its clinical application is limited due to individual differences in efficacy among patients and un-confirmed safety. 1,25 Dihydroxyvitamin D3 （1,25（OH）2D3） has been shown to be involved in a variety of physiological processes, including immune response regulation. In the present study we explored the role of 1,25（OH）2D3 pretreatment for immunotherapy.Methods Seventy-five BALB/c mice were randomly divided into five groups （15 mice per group）. The mouse allergic asthma model was established by intra-peritoneal injection of ovalbumin （OVA, 10 μg） and aluminium hydroxide （2 mg）as an adjuvant. Intra-peritoneal injection of 50 ng of 1,25（OH）2D3 served as a pretreatment, subcutaneous injection of OVA （100 μg） as an immunotherapy, and 1% OVA inhalation as a challenge. Histopathological analysis was performed on four mice per group. The number of cells and their classification in bronchoalvolar lavage （BAL） fluid were assayed.Levels of serum OVA-specific immunoglobulin E （slgE） and IFN-Y, IL-4, IL-5 and IL-10 in BAL fluid were measured by ELISA.Results After 1,25（OH）2D3 pretreatment, immunotherapy could significantly inhibit the infiltration of inflammatory cells into lung tissues and BAL fluid of mice with allergic asthma when compared with un-treated animals （eosinophils：（7.46±1.34）×104/ml vs. （13.41±1.67）×104/ml, P ＜0.05）. In addition, levels of IL-4 （（36.g1±7.87） pg/ml vs. （43.70±6.42）pg/ml, P ＞0.05） and IL-5 （（41.97±7.93） pg/ml vs. （60.14±8.35） pg/ml, P ＜0.05） in BAL fluid and serum slgE （（0.42±0.05）vs. （0.75±0.06） OD units, P ＜0.05） were profoundly reduced. However, the IL-10 level in BAL fluid was significantly increased （（67.74±6.57） pg/ml vs. （44.62±8.81） pg/ml, P ＜0.05）.Conclusions These results indicated that 1,25（OH）2D3 pretreatment enhanced the inhibitory effects of immunotherapy on allergic airway inflammation. In the treatment of allergic diseases, 1,25（OH）2D3 pretreatment may be beneficial for improving the efficacy of immunotherapy.展开更多
基金supported by a 2-Year Research Grant of Pusan National University
文摘1,25-dihydroxyvitamin D3 （VD3）, an active form of Vitamin D, is photosynthesized in the skin of vertebrates in response to solar ultraviolet B radiation （UV-B）. VD3 deficiency can cause health problems such as immune disease, metabolic disease, and bone disorders. It has also been demonstrated that VD3 is involved in reproductive functions. Female sex hormones such as estrogen and progesterone are biosynthesized mainly in ovarian granulosa cells as the ovarian follicle develops. The functions of sex hormones include regulation of the estrus cycle and puberty as well as maintenance of pregnancy in females. In this study, we isolated granulosa cells from porcine ovaries and cultured them for experiments. To examine the effects of VD3 on ovarian granulosa cells, the mRNA and protein levels of genes were analyzed by Real-time PCR and Western blotting assay. Production of progesterone from granulosa cells was also measured by ELISA assay. As a result, transcriptional and translational regulation of progesterone biosynthesis-related genes in granulosa cells was significantly altered by VD3. Furthermore, progesterone concen- trations in porcine granulosa cell-cultured media decreased in response to VD3. These results show that VD3 was a strong regulator of sex steroid hormone production in porcine granulosa cells, suggesting that vitamin D deficiency may result in inappropriate sexual development of industrial animals and eventually economic loss.
基金This research was supported by TETFUND-IBR and TETFUNDAST&D with reference number UN/VC/T/19/N.2.
文摘Objective:To evaluate the development of ovarian follicles in female albino rats following vitamin D3 supplementation.Methods:Eighteen prepubertal female albino rats,aged 3-4 weeks,weighing(70.25±9.16)g,were assigned to three groups(n=6 in each group).Group A was treated with 5.00 mL/kg of distilled water and served as the control group,group B was treated with 0.025 mg/kg of vitamin D3 dissolved in distilled water,and group C was treated with 0.125 mg/kg of vitamin D3 dissolved in distilled water.All treatments were administered orally,twice weekly for 28 days.Blood and ovaries were harvested under anaesthesia.Serum vitamin D3 levels were determined by using spectrophotometric method.Ovaries were processed for histology and every10th hematoxylin and eosin stained-section was selected for histomorphometry.The number of follicles at each developmental stage was estimated.Results:Both 0.025 mg/kg and 0.125 mg/kg of vitamin D3 significantly increased serum concentrations of vitamin D3 and calcium(P<0.05),but did not alter inorganic phosphorus concentration(P>0.05).The control group had fewer growing follicles(primary,secondary and antral follicles)and more non-growing follicles(primordial and atretic follicles)when compared with the vitamin D3-supplemented groups(P<0.05).Vitamin D3 at 0.025 mg/kg significantly increased antral follicles and corpora lutea counts(P<0.05).Vitamin D3 at 0.125 mg/kg significantly increased total,primordial and atretic follicles counts(P<0.05),but significantly decreased primary,secondary,antral follicles count,ovarian weight,relative ovarian weight,and ovarian surface area when compared with the control group and rats treated with 0.025 mg/kg of vitamin D3(P<0.05).Conclusions:Vitamin D3 supplementation at 0.025 mg/kg can enhance optimal ovarian follicle recruitment and development in female rats.
文摘<span style="font-family:Verdana;"><strong>Objectives:</strong> Rheumatoid arthritis is sometimes misdiagnosed for other diseases, like psoriatic arthritis, erosive OA, viral arthritis, reactive arthritis, IBD arthritis, Lyme’s disease, and palindromic rheumatism. Secondary hyperparathyroidism was not included in the differential diagnosis of RA, though it sometimes presents with joint pains and tenderness, and even arthritis. Fibromyalgia is a psychosomatic disorder characterized by chronic widespread pain and tender areas. Mimicry of some manifestations of these diseases sometimes results in misdiagnosis as RA. <strong>Methods:</strong> Two hundred patients previously diagnosed as RA from outpatient clinics in Al-Azhar Faculty of Medicine, attended as not responding to medical treatment of RA. All patients were subjected to a re-evaluation of disease activity including HAQ, and DAS 28, CDAI, and SDAI. Also, we measured serum vitamin D3, PTH, total and ionized Calcium, Phosphorus, Uric acid, ACPA, and other routine lab. All patients were exposed to various radiological imaging modalities. <strong>Results:</strong> Cases not responding to RA treatment were reevaluated and were found to have a syndrome of fibromyalgia associated with vitamin D3 deficiency and secondary hyperparathyroidism. <strong>Conclusions:</strong> Fibromyalgia/Hyperparathyroidism syndrome is an underdiagnosed disease, which results from chronic vitamin D3 deficiency. SHPT can cause bone erosions, which are mostly shaggy in appearance and distributed in the radiocarpal, radioulnar, metacarpophalangeal and distal interphalangeal joints, in contrast to that which predominate proximal IP joints of rheumatoid arthritis. Radiology of FM/HPT syndrome patients revealed a sign of spur-like excrescences in terminal finger tufts unilaterally or bilaterally, which we think is pathognomonic.</span>
文摘<strong>Objective:</strong><span style="font-family:Verdana;"> To determine and compare the effect of vitamin D3 supplementation on modifying the disease severity in cystic fibrosis (CF) and non</span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis pediatric patients.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Methods: </span></b><span style="font-family:Verdana;">A randomized clinical trial evaluating the role of oral vitamin D3 supplementation for six months, was performed in forty patients with CF and non</span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis under the age of 18 years with vitamin D deficiency or insufficiency. The primary outcome was to reach the sufficient Vitamin D level, the secondary outcome was to reevaluate bronchiectasis severity by following up the frequency, severity of pulmonary exacerbations and lung function after vitamin D3 supplementation.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Results:</span></b><b><span style="font-family:""> </span></b><span style="font-family:Verdana;">Forty patients completed the trial. The percentage of improvement of vitamin D level after vitamin D3 supplementation for six months was significantly higher in CF (88.3%) than non</span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis patients (59.82%)</span><span style="font-family:""> </span><span style="font-family:Verdana;">(P =</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.03).</span><span style="font-family:""> </span><span style="font-family:Verdana;">Additionally, moderate to severe pulmonary exacerbations significantly decreased by more than 60%, 45% (P</span><span style="font-family:""> </span><span style="font-family:Verdana;">=</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.001,</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.005) and frequent exacerbations decreased by 15%, 10% (P</span><span style="font-family:""> </span><span style="font-family:Verdana;">=</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.327, 0.490), while the forced expiratory volume in 1 (FEV1) significantly increased by 17% and 15% in non CF bronchiectasis and CF patients respectively (p</span><span style="font-family:""> </span><span style="font-family:Verdana;"><</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">0.001).</span><b><span style="font-family:Verdana;"> Conclusions: </span></b><span style="font-family:Verdana;">Vitamin D3 therapy was effective in decreasing the frequency and severity of pulmonary exacerbations and preserving lung function. Thereby, improving the disease severity even more in non</span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis than CF patients.</span>
基金Supported by Research Grants ETT022/2006 and ETT151/2009 from the Ministry of Health,HungaryTáMOP-4.2.1/B-09/1/KONV-2010-0005 from Creating the Center of Excellence at the University of Szegedsupported by the European Union and cofinanced by the European Regional Fund
文摘AIM:The effects of vitamin D3 have been investigated on various tumors, including colorectal cancer (CRC). 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1), the enzyme that inactivates the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25-D3), is considered to be the main enzyme determining the biological halflife of 1,25-D3. During colorectal carcinogenesis, the expression and concentration of CYP24A1 increases significantly, suggesting that this phenomenon could be responsible for the proposed efficacy of 1,25-D3 in the treatment of CRC. The aim of this study was to investigate the anti-tumor effects of vitamin D3 on the human CRC cell line Caco-2 after inhibition of the cytochrome P450 component of CYP24A1 activity. METHODS:We examined the expression of CYP24A1 mRNA and the effects of 1,25-D3 on the cell line Caco-2 after inhibition of CYP24A1. Cell viability and proliferation were determined by means of sulforhodamine-B staining and bromodeoxyuridine incorporation, respectively, while cytotoxicity was estimated via the lactate dehydrogenase content of the cell culture supernatant. CYP24A1 expression was measured by realtime reverse transcription polymerase chain reaction. A number of tetralone compounds were synthesized to investigate their CP24A1 inhibitory activity. RESULTS:In response to 1,25-D3, CYP24A1 mRNA expression was enhanced significantly, in a time- and dose-dependent manner. Caco-2 cell viability and proliferation were not influenced by the administration of 1,25-D3 alone, but were markedly reduced by coadministration of 1,25-D3 and KD-35, a CYP24A1-inhibiting tetralone. Our data suggest that the mechanism of action of co-administered KD-35 and 1,25-D3 does not involve a direct cytotoxic effect, but rather the inhibition of cell proliferation. CONCLUSION:These findings demonstrate that the selective inhibition of CYP24A1 by compounds such as KD-35 may be a new approach for enhancement of the anti-tumor effect of 1,25-D3 on CRC.
文摘A new six intraperitoneal injection insulin-mimetic vanadyl(Ⅱ) compounds [(VD3^-1)(VO^+2)(AAn^-1)](where(n=1~6);AA1=isoleucine, AA2=threonine, AA3=proline, AA4=phenylalanine, AA5=lysine and AA6=glutamine) were synthesized by the chemical reactions between vitamin D3(VD3), VOSO4 and amino acids(AAn) with equal molar ratio 1∶1∶1 in neutralized media. The structures of these complexes were elucidated by spectroscopic methods like, infrared and solid reflectance spectroscopes. Magnetic moments and electronic spectra reveal square pyramid geometrical structure of the complexes. The infrared spectra assignments of these complexes revealed that the chelation towards vanadyl(Ⅳ) ions existed via deprotonation of the hydroxyl group of VD3 drug ligand and so amino acids act as bidentate ligand via N-amino and O-carboxylate groups. The anti-diabetic efficiency of these complexes were evaluated against streptozotocin induced diabetic male albino rats.
基金supported by grants from the National Natural Science Foundation of China (81773800 and 81471070)the CAMS Innovation Fund for Medical Sciences (CIFMS, 2016I2M-1-010 to Xiao-wei Zhang and 2016-I2M-1-012 to Wen Jin)
文摘Vitamin D_3 has been found to produce therapeutic effects on obesity-associated insulin resistance and dyslipidemia through its potent anti-inflammatory activity, but the precise immunomodulatory mechanism remains poorly understood. In the present study we found that 1,25-dihydroxyvitamin D_3[1,25(OH)_2D_3], the biologically active form of vitamin D_3, significantly attenuated monosodium glutamate(MSG)-induced obesity and insulin resistance as indicated by body weight reduction, oral glucose tolerance improvement, and a glucose infusion rate increase as detected with hyperinsulinemiceuglycemic clamp. Moreover, 1,25(OH)_2D_3 not only restored pancreatic islet functions but also improved lipid metabolism in insulin-targeted tissues. The protective effects of 1,25(OH)_2D_3 on glycolipid metabolism were attributed to its ability to inhibit an obesity-activated inflammatory response in insulin secretory and targeted tissues, as indicated by reduced infiltration of macrophages in pancreas islets and adipose tissue while enhancing the expression of Tgf-β1 in liver tissue, which was accompanied byincreased infiltration of Treg cells in immune organs such as spleen and lymph node as well as in insulintargeted tissues such as liver, adipose, and muscle. Together, our findings suggest that 1,25(OH)_2D_3 serves as a beneficial immunomodulator for the prevention and treatment of obesity or metabolic syndrome through its anti-inflammatory effects.
文摘Background Several studies found that vitamin D3 might alter glucose metabolism,protect kidney from injury and even proposed the mechanisms.But results from previous studies have been conflicting.The aim of this study was to evaluate the efficacy and safety of vitamin D3 in patients with diabetic nephropathy.The underlying mechanism of vitamin D3 decreasing proteinuria is also discussed.Methods We conducted a search of English and Chinese articles using database of Pubmed,Embase,Sinomed,CNKI,Wanfang and clinical trial register centers,for randomized controlled trials of vitamin D3 in diabetic nephropathy patients.Two reviewers performed independently.Meta-analysis was used when studies were homogeneous enough.Results Twenty studies,including 1 497 patients with diabetic nephropathy,were involved in this systemic review.Vitamin D3-treated patients with diabetic nephropathy had a statistically significant reduction in 24-hour proteinuria （weighted mean difference-0.44,95% CI-0.54 to-0.34,Z=8.80,P 〈0.000 01） and urine albumin/creatine ratio （standardized mean difference-0.29,95% CI-0.48 to-0.10,Z=2.96,P=0.003）.But vitamin D3 supplementation did not significantly reduce blood pressure and hemoglobin A1c compared with control group.The potential mechanisms about the renal protection of vitamin D3,including the inhibition of rennin-angiotensin system,the protection of kidney from inflammation,fibrosis and the structure change of kidney are discussed.In addition,vitamin D3 did not significantly increase the incidence of adverse effects,including total adverse effects,gastrointestinal adverse effects and fluctuation of blood pressure.Conclusions Vitamin D3 can ameliorate proteinuria and protect kidney from injury in patients with diabetic nephropathy.This renoprotective effect is independent of blood pressure and glucose reduction.And it does not increase any adverse effects than control,even in combination therapy with angiotensin converting enzyme inhibitors/angiotensin receptor blockers.But due to the limited randomized controlled trials of high quality,more clinical researches should be taken in the future.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 30872341）.
文摘Background Allergen-specific immunotherapy can induce immune tolerance to specific allergens by regulating immune status of individuals. However, its clinical application is limited due to individual differences in efficacy among patients and un-confirmed safety. 1,25 Dihydroxyvitamin D3 （1,25（OH）2D3） has been shown to be involved in a variety of physiological processes, including immune response regulation. In the present study we explored the role of 1,25（OH）2D3 pretreatment for immunotherapy.Methods Seventy-five BALB/c mice were randomly divided into five groups （15 mice per group）. The mouse allergic asthma model was established by intra-peritoneal injection of ovalbumin （OVA, 10 μg） and aluminium hydroxide （2 mg）as an adjuvant. Intra-peritoneal injection of 50 ng of 1,25（OH）2D3 served as a pretreatment, subcutaneous injection of OVA （100 μg） as an immunotherapy, and 1% OVA inhalation as a challenge. Histopathological analysis was performed on four mice per group. The number of cells and their classification in bronchoalvolar lavage （BAL） fluid were assayed.Levels of serum OVA-specific immunoglobulin E （slgE） and IFN-Y, IL-4, IL-5 and IL-10 in BAL fluid were measured by ELISA.Results After 1,25（OH）2D3 pretreatment, immunotherapy could significantly inhibit the infiltration of inflammatory cells into lung tissues and BAL fluid of mice with allergic asthma when compared with un-treated animals （eosinophils：（7.46±1.34）×104/ml vs. （13.41±1.67）×104/ml, P ＜0.05）. In addition, levels of IL-4 （（36.g1±7.87） pg/ml vs. （43.70±6.42）pg/ml, P ＞0.05） and IL-5 （（41.97±7.93） pg/ml vs. （60.14±8.35） pg/ml, P ＜0.05） in BAL fluid and serum slgE （（0.42±0.05）vs. （0.75±0.06） OD units, P ＜0.05） were profoundly reduced. However, the IL-10 level in BAL fluid was significantly increased （（67.74±6.57） pg/ml vs. （44.62±8.81） pg/ml, P ＜0.05）.Conclusions These results indicated that 1,25（OH）2D3 pretreatment enhanced the inhibitory effects of immunotherapy on allergic airway inflammation. In the treatment of allergic diseases, 1,25（OH）2D3 pretreatment may be beneficial for improving the efficacy of immunotherapy.
