Effect of vitamin D drops combined with insulin aspart in the treatment of gestational diabetes mellitus and its influence on serum 1, 25(OH) 2D 3 and RBP4 levels / 中国医师杂志

Objective:To investigate the clinical efficacy of vitamin D drops combined with insulin aspart in the treatment of gestational diabetes mellitus (GDM), and the effect of vitamin D drops on the serum levels of 1, 25 dihydroxyvitamin D 3 [1, 25(OH) 2D 3] and retinol binding protein 4 (RBP4). Methods:A total of 94 GDM patients admitted to the Baoding Second Central Hospital from March 2019 to March 2021 were selected and randomly divided into an observation group and a control group with 47 cases each using a random number table method. The control group received subcutaneous injection of insulin aspartate for treatment, while the observation group received oral vitamin D drops for treatment. After 4 weeks of continuous treatment, the blood glucose control effect and adverse reactions were observed in both groups. The glucose metabolism indicators of the two groups were compared before and after treatment, including fasting blood glucose (FPG), 2-hour postprandial blood glucose (2-hour PG), insulin resistance index (HOMA-IR), and pancreatic islets β Cell Function Index (HOMA-β) and serum levels of 1, 25(OH) 2D 3, RBP4, lipoprotein related phospholipase A2 (Lp-PLA2), and vascular cell adhesion molecule-1 (VCAM-1). All patients were followed up until the end of pregnancy, and Statistical analysis was conducted on the adverse outcomes of two groups of mothers and infants. Results:The time to reach the standard for FPG and 2-hour PG in the observation group, as well as the time for both to reach the standard were significantly shorter than those in the control group (all P<0.05). There was no statistically significant difference in the incidence of dawn phenomenon and hypoglycemia between the observation group and the control group (all P>0.05). After treatment, FPG and 2-hour PG in both groups were significantly reduced compared to those before treatment (all P<0.05); However, after treatment, there was no statistically significant difference between the groups (all P>0.05). Compared with before treatment, HOMA-IR in both groups significantly decreased (all P<0.05), All HOMA- β significantly increased (all P<0.05); And the improvement was more significant in the observation group (all P<0.05). After treatment, the serum levels of 1, 25(OH) 2D 3 in the observation group significantly increased compared to that before treatment ( P<0.05), but there was no significant change in the control group before and after treatment ( P>0.05). After treatment, the levels of serum RBP4, Lp-PLA2, and VCAM-1 in both groups significantly decreased compared to those before treatment (all P<0.05); After treatment, the serum levels of RBP4, Lp-PLA2, and VCAM-1 in the observation group were lower than those in the control group (all P<0.05). The incidence of adverse maternal and neonatal outcomes in the observation group was 14.9%(7/47) and 10.6%(5/47), respectively, which were lower than those in the control group [34.0%(16/47) and 27.7%(13/47)] (all P<0.05). There were 8 cases of hypoglycemia in 94 patients (3 in the observation group and 5 in the control group), and no other adverse events occurred. Conclusions:The combination of vitamin D drops and insulin aspartate in the treatment of GDM can safely, effectively, quickly, and steadily control patients′ blood sugar, improve IR and pancreatic islets β The effect of cell function on reducing the incidence of adverse maternal and fetal outcomes may be related to increasing serum 1, 25(OH) 2D 3 levels and down-regulating the expression levels of serum RBP4, Lp-PLA2, and VCAM-1.

Effects of 1, 25-dihydroxyvitamin D3 on experimental periodontitis and AhR/NF-κB/NLRP3 inflammasome pathway in a mouse model

Abstract Vitamin D has been known to have important regulatory functions in inflammation and immune response and shows inhibitory effects on experimental periodontitis in animal models. However, the potential mechanism has yet to be clarified. Recent studies have highlighted Aryl hydrocarbon receptor (AhR) and its downstream signaling as a crucial regulator of immune homeostasis and inflammatory regulation. Objective: This study aimed to clarify the effect of 1,25-dihydroxyvitamin D3 (VD3) on experimental periodontitis and AhR/nuclear factor-κB (NF-κB)/NLR pyrin domain-containing 3 (NLRP3) inflammasome pathway in the gingival epithelium in a murine model. Methodology: We induced periodontitis in male C57BL/6 wild-type mice by oral inoculation of Porphyromonas gingivalis (P. gingivalis), and subsequently gave intraperitoneal VD3 injection to the mice every other day for 8 weeks. Afterwards, we examined the alveolar bone using scanning electron microscopy (SEM) and detected the gingival epithelial protein using western blot analysis and immunohistochemical staining. Results: SEM images demonstrated that alveolar bone loss was reduced in the periodontitis mouse model after VD3 supplementation. Western blot analyses and immunohistochemical staining of the gingival epithelium showed that the expression of vitamin D receptor, AhR and its downstream cytochrome P450 1A1 were enhanced upon VD3 application. Additionally, VD3 decreased NF-κB p65 phosphorylation, and NLRP3, apoptosis-associated speck-like protein, caspase-1, interleukin-1β (IL-1β) and IL-6 protein expression. Conclusions: These results implicate the alleviation of periodontitis and the alteration of AhR/NF-κB/NLRP3 inflammasome pathway by VD3 in the mouse model. The attenuation of this periodontal disease may correlate with the regulation of AhR/NF-κB/NLRP3 inflammasome pathway by VD3.

1,25-Dihydroxyvitamin D3 protects obese rats from metabolic syndrome promoting regulatory T cell-mediated resolution of inflammation

Vitamin D 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 [1,25(OH)D], the biologically active form of vitamin D, 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 hyperinsulinemic-euglycemic clamp. Moreover, 1,25(OH)D not only restored pancreatic islet functions but also improved lipid metabolism in insulin-targeted tissues. The protective effects of 1,25(OH)D 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 in liver tissue, which was accompanied by increased infiltration of Treg cells in immune organs such as spleen and lymph node as well as in insulin-targeted tissues such as liver, adipose, and muscle. Together, our findings suggest that 1,25(OH)D serves as a beneficial immunomodulator for the prevention and treatment of obesity or metabolic syndrome through its anti-inflammatory effects.

Effect of 1,25-dihydroxyvitamin D3 on renal expression of TGF-1/Smads in diabetic nephropathy rats / 中国基层医药

Objective To explore the effects of 1,25-dihydroxyvitamin D3 on renal expression of TGFβ1,Smad3 and Smad7.Methods 40 Sprague-Dawley mts were randomized into 4 groups:normal control rats (group A),diabetic nephropathy group (group B),small dose 1,25-dihydroxyvitamin D treatment group (0.5 μg · kg-1 · d-1,group C) and large dose 1,25-dihydroxyvitamin D treatment group (1 μg · kg-1 · d-1,group D),each group had 10 rats.After 12 weeks,the renal function,blood glucose,glycosylated hemoglobin and the urine trace albumin content of each rats were tested.Results The biochemical indicators in group B were higher than those in group A,(t =-16.566,P ＜0.05;t =-16.949,P ＜0.05;t =-11.844,P ＜0.05;t =-19.778,P ＜0.05;t =-14.013,P ＜ 0.05).Compared with group B,the biochemical indicators and the expression of TGFβ1,Smad3 mRNA reduced in group C and group D,and the expression of Smad7 mRNA increased (F =37.892,P ＜ 0.05;F =70.068,P ＜ 0.05;F =21.95,P ＜0.05;F =77.619,P ＜0.05;F =37.670,P ＜0.05;F =1062.562,P ＜0.05;F =2463.789,P ＜0.05;F =81.745,P ＜ 0.05).There were no significant differences between group C and group D (t =0.538,P＞0.05;t =1.737,P＞0.05;t =0.671,P＞0.05;t =1.763,P ＞0.05;t =0.997,P ＞0.05;t =1.653,P ＞0.05;t=1.543,P＞0.05;t =-1.313,P ＞0.05).Conclusion 1,25-dihydroxyvitamnin D3 has protective effect on diabetic nephropathy rats model,the mechanism may be associated with inhibiting the expression of TGF β1 and Smad3,increasing the expression of Smad7.

mTOR signaling pathway for regulating inhibition of 1,25 dihydroxyvitamin D3 on Hep-2 cells proliferation in laryngeal carcinoma / 国际检验医学杂志

Objective To explore the inhibition role of 1 ,25 dihydroxyvitamin D3 on laryngeal cancer Hep‐2 cell proliferation and its influence on mTOR signal pathway .Methods Hep‐2 cells were treated with different concentrations of 1 ,25 dihydroxyvitamin D3 (10-8 ,10-7 ,10-6mol/L) for 24 ,48 ,72 h respectively .The proliferation situation of Hep‐2 cells was detected by the MTT meth‐od and the inhibition rate was calculated .The effect of 1 ,25 dihydroxyvitamin D3 on Hep‐2 cell cycle distribution was analyzed by flow cytometry .The influence of 1 ,25 dihydroxyvitamin D3 on mTOR signaling pathway was detected by Western blot .Results Different concentrations of 1 ,25 dihydroxyvitamin D3 could inhibit the proliferation of Hep‐2 cells ,changed the cell cycle distribu‐tion and increased the proportion of Hep‐2 cells in G0/G1 phase .The expressions of TSC1 and TSC2 protein after 1 ,25 dihydroxyvi‐tamin D3 intervention were increased compared with the control group (P<0 .01) ,while the Rheb protein expression was signifi‐cantly decreased(P<0 .01):mTOR protein and phosphorylation level were significantly decreased compared with the control group (P<0 .01) ,the decrease of mTOR protein phosphorylation was especially obvious (P<0 .01);4EBP‐1 protein expression was in‐creased compared with the control group (P<0 .01) .Conclusion 1 ,25‐dihydroxyvitamin D3 alters the Hep‐2 cell cycle distribution , affects the protein expression of mTOR signaling pathway ,thus inhibits the cell proliferation .

The expression and clinical significance of serum 1, 25-dihydroxyvitamin D3 in different stages of diabetic nephropathy patients / 中国综合临床

Objective To study the expression and clinical significance of serum 1,25-dihydroxyvitamin D3 in different stages of diabetic nephropathy patients.Methods Ninety-eight cases of diabetics were selected as our subjects in observation group,who were hospitalized in Tieying Hospital of Fengtai District of Beijing from January 2010 to December 2014.They were divided into diabetics group(36 cases,UAER ＜30 mg/24 h),microalbuminuria group(32 cases,UAER was 30-300 mg/24 h),massive proteinuria group (30cases,UAER＞300 mg/24 h).One hundred healthy persons were selected as a normal control group over the same period.The changes of fasting blood glucose,course of disease,blood lipid,serum creatinine and serum 1,25-dihydroxyvitamin D3 in all groups were recorded.Results Fasting blood glucose,serum creatinine and serum 1,25-dihydroxyvitamin D3 were (8.97±2.3) mmol/L,(76.2±19.5) μmol/L,(28.9±13.6) μg/L in observation group,and (4.7±0.4) mmol/L,(63.1±12.0) μmol/L,(70.1±21.3) μg/L in control group respectively,the difference between the two group was statistically significant (P =0.031,0.046,0.028).Serum 1,25-dihydroxyvitamin D3 was (52.68±20.91) μg/L in patients of diabetics group,(31.40±15.23) μg/L in microabuminuria group,(15.76±7.81) μg/L in massive proteinuria group,the difference among the three group was statistically significant (P =0.036).Serum 1,25-dihydroxyvitamin D3 of microabuminuria group and massive proteinuria group were lower than of diabetics group,of massive proteinuria group was lower than of microabuminuria group(P＜0.05).Serum 1,25-dihydroxyvitamin D3 was negatively correlated with the cause of disease(r=-0.301),fasting blood glucose (r =-0.281) and serum creatinine (r =-0.536) in patients with type 2 diabetes,the difference was statistically significant (P ＜ 0.05).Conclusion Serum 1,25-dihydroxyvitamin D3 in patients with diabetic nephropathy decrease in different degree,which reflects the severity of renal damage.The results indicate that reduction of serum 1,25-dihydroxyvitamin D3 may be involved in the occurrence and development of diabetic nephropathy

The Association of Low-energy Spine Fractures and Vitamin D Inadequacy: A Case-control Study

STUDY DESIGN: Retrospective study. OBJECTIVES: To compare serum vitamin D levels in elderly patients with or without osteoporotic spinal compression fractures (OSCFs) and to identify relationships between the serum vitamin D level and other variables, such as age, bone mineral density (BMD), and bone turnover markers (osteocalcin and C-telopeptide). SUMMARY OF LITERATURE REVIEW: Vitamin D plays a key role in calcium metabolism in the bone tissue. Vitamin D deficiency can lead to decreased BMD and an increased risk of falls and of osteoporotic fractures. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 95 elderly patients (≥60 years) with OSCFs (fracture group) and 118 subjects who had been diagnosed with osteoporosis without OSCFs (control group). Serum vitamin D levels were contrasted between the two groups taking into account other factors such as patient age, sex, and seasonal variations. For all the patients, we also evaluated the correlation between the vitamin D level and the patient age, BMD, and bone turnover markers. RESULTS: The mean of the serum 25(OH) vitamin D3 levels was significantly lower in the fracture group than in the control group. There were significant differences in the 25(OH) vitamin D3 levels in autumn. In all patients, the mean serum 25(OH) vitamin D3 levels were the highest in autumn and the lowest in spring. Furthermore, the mean serum 25(OH) vitamin D3 levels were significantly correlated with patient age and BMD. CONCLUSIONS: A low serum vitamin D level might be a risk factor of OSCFs in elderly patients.

Treatment with 1,25(OH)2D3 induced HDAC2 expression and reduced NF-κB p65 expression in a rat model of OVA-induced asthma

Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may influence asthma pathogenesis; however, its roles in regulating specific molecular transcription mechanisms remain unclear. We aimed to investigate the effect of 1,25(OH)2D3 on the expression and enzyme activity of histone deacetylase 2 (HDAC2) and its synergistic effects with dexamethasone (Dx) in the inhibition of inflammatory cytokine secretion in a rat asthma model. Healthy Wistar rats were randomly divided into 6 groups: control, asthma, 1,25(OH)2D3 pretreatment, 1,25(OH)2D3 treatment, Dx treatment, and Dx and 1,25(OH)2D3 treatment. Pulmonary inflammation was induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA). Inflammatory cells and cytokines in the bronchoalveolar lavage (BAL) fluid and histological changes in lung tissue were examined. Nuclear factor kappa B (NF-κB) p65 and HDAC2 expression levels were assessed with Western blot analyses and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Enzyme activity measurements and immunohistochemical detection of HDAC2 were also performed. Our data demonstrated that 1,25(OH)2D3 reduced the airway inflammatory response and the level of inflammatory cytokines in BAL. Although NF-κB p65 expression was attenuated in the pretreatment and treatment groups, the expression and enzyme activity of HDAC2 were increased. In addition, 1,25(OH)2D3 and Dx had synergistic effects on the suppression of total cell infusion, cytokine release, and NF-κB p65 expression, and they also increased HDAC2 expression and activity in OVA/OVA rats. Collectively, our results indicated that 1,25(OH)2D3 might be useful as a novel HDAC2 activator in the treatment of asthma.

Effect of 1,25-dihydroxyvitamin D3 on mast cells tryptase in asthmatic guinea pigs

Objective: To explore the effect of 1,25-dihydroxyvitamin D3 on the mast cell tryptase (MCT) in asthmatic guinea pigs. Methods: A total of 60 male or female healthy guinea pigs were randomly divided into control group (group A), asthmatic group (group B), and 1,25-dihydroxyvitamin D3 group (group C), with 20 cases in each group. To establish asthmatic guinea pig models, 1mL peanut oil was filled into stomach in the morning in group A and group B, and 1mL peanut oil with 1,25-dihydroxyvitamin D3 was filled into stomach in group C. Airway resistance (Re) of asthmatic guinea pigs was detected, and the bronchoalveolar lavage fluid (BALF) cells were counted. Lung tissue with HE and MCT immunohistochemical staining were used to observe the pathological changes in lung tissue and the distribution of MCT. Results: After injection of different concentration of acetylcholine chloride, the Re in group B and group C were increased significantly compared with group A (P<0.05); compared with group B, the Re in group C were decreased significantly (t=-5.385,-5.761,-6.184,-13.574, P<0.05); the total number of BALF cells and eosinophils were increased significantly in group B and C (t=19.618, 9.598, 10.854, 5.388, P<0.05); compared with group B, the total number of BALF cells and eosinophils in group C was decreased significantly (t=-5.555,-5.392, P<0.05); the number of tryptase positive cells in group B was increased significantly than that in group A (t=21.312, P<0.05), and in addition to the alveolar septum and submucosa, the cells were also distributed around blood vessels and outside the cells; the number of tryptase positive cells in group C was decreased significantly compared with group B, and the difference was statistically significant (t=5.043, P<0.05). Conclusions: After the asthmatic guinea pigs are treated with 1,25-dihydroxyvitamin D3, their BALF, Re, infiltration degree of inflammatory cells in the trachea and lung tissue and airway inflammatory reaction are reduced significantly. 1,25-dihydroxyvitamin D3 has a certain inhibiting effect on the activation of mast cells and the release of MCT granules.

Effect of 1, 25-dihydroxyvitamin D3 on mast cells tryptase in asthmatic guinea pigs

Objective:To explore the effect of 1,25-dihydroxyvitamin D3 on the mast cell tryptase (MCT) in asthmatic guinea pigs. Methods:A total of 60 male or female healthy guinea pigs were randomly divided into control group (group A), asthmatic group(group B), and 1,25-dihydroxyvitamin D3 group(group C), with 20 cases in each group. To establish asthmatic guinea pig models, 1ml peanut oil was filled into stomach in the morning in group A and group B , and 1ml peanut oil with 1,25-dihydroxyvitamin D3 was filled into stomach in group C. Airway resistance (Re) of asthmatic guinea pigs was detected, and the bronchoalveolar lavage fluid (BALF) cells were counted. Lung tissue with HE and MCT immunohistochemical staining were used to observe the pathological changes in lung tissue and the distribution of MCT. Results:After injection of different concentration of acetylcholine chloride, the Re in group B and group C were increased significantly compared with group A (P<0.05);compared with group B, the Re in group C were decreased significantly (t=-5.385, -5.761, -6.184,-13.574, P<0.05);the total number of BALF cells and eosinophils were increased significantly in group B and C (t=19.618, 9.598, 10.854, 5.388, P<0.05);compared with group B, the total number of BALF cells and eosinophils in group C was decreased significantly (t=-5.555,-5.392, P<0.05);the number of tryptase positive cells in group B was increased significantly than that in group A (t=21.312, P<0.05), and in addition to the alveolar septum and submucosa, the cells were also distributed around blood vessels and outside the cells; the number of tryptase positive cells in group C was decreased significantly compared with group B, and the difference was statistically significant (t=5.043, P<0.05). Conclusions:After the asthmatic guinea pigs are treated with 1,25-dihydroxyvitamin D3, their BALF, Re, infiltration degree of inflammatory cells in the trachea and lung tissue and airway inflammatory reaction are reduced significantly. 1,25-dihydroxyvitamin D3has a certain inhibiting effect on the activation of mast cells and the release of MCT granules.

The mechanism played by 1,25-dihydroxyvitamin D3 in treating renal fibrosis in diabetic nephropathy / 中华内分泌代谢杂志

Objective To observe the effects of 1,25-dihydroxyvitamin D3 on the expressions of transforming growth factor-β1(TGF-β1), fibronectin(FN),and vascular endothelial growth factor(VEGF) in rats with diabetic nephropathy(DN), and to elucidate the protective mechanism played by 1,25-dihydroxyvitamin D3. Methods DN models were estabolished by injecting streptozotoein ( STZ ) into male SD rats, which were divided into TGF-β1 overexpression group, TGF-β1 overexpression plus vitamin D3 group, TGF-β1 low-expression group, TGF-β1 low-expression plus vitamin D3 group, TGF-β1 normal-expression group, and TGF-β1 normal-expression plus vitamin D3 group. After 1,25-dihydroxyvitamin D3 treatment for 37 days, renal function and blood biochemical parameters were evaluated. The morphology and fibrosis of kidney tissues were observed. The expressions of TGF-β1, FN, and VEGF in kidney cortex were measured by immunohistochemistry, realtime PCR, and Western blotting. Results The levels of cholesterol, triglyceride, creatinine,plasma glucose, HbA1C , and 24 h urinary protein were lower in vitamin D3treated groups than those in corresponding control groups(P<0. 05). The degree of renal fibrosis was raised with the increased level of TGF-β1. Vitamin D3 treatment decreased the fibrosis in diabetic kidney. There were significant differences in the mRNA and protein expressions of TGF-β1 in three control groups(P<0. 05). With the increased levels of TGF-β1, the expressions of FN and VEGF were increased. The expressions of TGF-β1, FN, and VEGF were lowered by vitamin D3compared with the corresponding control groups(P<0. 05). Conclusion 1,25-dihydroxy-vitamin D3 may protect the renal tissure in diabetic rats via inhibiting the expressions of TGF-β1, FN, and VEGF in the kidney.

Effect of 1,25-dihydroxyvitamin D3 on mast cells tryptase in asthmatic guinea pigs

OBJECTIVE@#To explore the effect of 1,25-dihydroxyvitamin D3 on the mast cell tryptase (MCT) in asthmatic guinea pigs.@*METHODS@#A total of 60 male or female healthy guinea pigs were randomly divided into control group (group A), asthmatic group (group B), and 1,25-dihydroxyvitamin D3 group (group C), with 20 cases in each group. To establish asthmatic guinea pig models, 1 mL peanut oil was filled into stomach in the morning in group A and group B, and 1 mL peanut oil with 1,25-dihydroxyvitamin D3 was filled into stomach in group C. Airway resistance (Re) of asthmatic guinea pigs was detected, and the bronchoalveolar lavage fluid (BALF) cells were counted. Lung tissue with HE and MCT immunohistochemical staining were used to observe the pathological changes in lung tissue and the distribution of MCT.@*RESULTS@#After injection of different concentration of acetylcholine chloride, the Re in group B and group C were increased significantly compared with group A (P < 0.05); compared with group B, the Re in group C were decreased significantly (t = -5.385, -5.761, -6.184, -13.574, P < 0.05); the total number of BALF cells and eosinophils were increased significantly in group B and C (t = 19.618, 9.598, 10.854, 5.388, P < 0.05); compared with group B, the total number of BALF cells and eosinophils in group C was decreased significantly (t = -5.555, -5.392, P < 0.05); the number of tryptase positive cells in group B was increased significantly than that in group A (t = 21.312, P < 0.05), and in addition to the alveolar septum and submucosa, the cells were also distributed around blood vessels and outside the cells; the number of tryptase positive cells in group C was decreased significantly compared with group B, and the difference was statistically significant (t = 5.043, P < 0.05).@*CONCLUSIONS@#After the asthmatic guinea pigs are treated with 1,25-dihydroxyvitamin D3, their BALF, Re, infiltration degree of inflammatory cells in the trachea and lung tissue and airway inflammatory reaction are reduced significantly. 1,25-dihydroxyvitamin D3 has a certain inhibiting effect on the activation of mast cells and the release of MCT granules.

Effect of 1,25-dihydroxyvitamin D3 on interleukin 17 expression in mice with asthma / 中华实用儿科临床杂志

Objective To explore the effects of interleukin 17 (IL-17) and 1,25-dihydroxyvitamin D3 [1,25-(OH)2VD3] on the pathogenesis of asthma.Methods Thirty-two Kunming mice were randomly divided into 4 groups:the control group (group A),the asthma group (group B),the 1,25-(OH)2VD3-treated group (group C) and the Dexamethasone-treated group (group D).The allergic mouse models were established by using ovalbumin (OVA).The behavioral changes of mice were observed and the number of leukocytes in the bronchoalveolar lavage fluid (BALF) were counted.HE staining was used to measure the histological changes of lung tissue.The levels of IL-17 and IgE in the BALF were detected by enzyme-linked immunosorbent assay (ELISA).Results The asthmatic symptoms were more severe in group A than those in the other groups,while they were relieved significantly in group C and group D when treated with 1,25-(OH)2VD3 or Dexamethasone.The number of leukocyte in groups B,C and D [(1.97 ± 0.23) × 108/L,(1.02 ±0.17) × 108/L,(0.95 ±0.14) × 108/L]were higher than those in group A[(0.56 ±0.16) × 108/L] (F =85.58,P ＜ 0.01),and lower in group C and group D than those in group B (all P ＜ 0.01),but there were no significant differences between group C and group D(P ＞0.05).The levels of IgE and IL-17 in group B were significantly higher than those in group A(all P ＜ 0.01).The levels of IgE and IL-17 in group B were significantly lower than those in group C and group D,but higher than those in group A(all P ＜0.01).No significant results were observed between group C and group D (all P ＞ 0.05).Conclusions IL-17 involves in the inflammation process of asthma,which promotes the respiratory inflammation.1,25-(OH)2VD3 may suppress IL-17 expression to relieve the respiratory inflammation in acute asthmatic mice,the effect of which is similar to that of Dexamethasone on asthma.

Effect of 1,25-dihydroxyvitamin D3 on cell proliferation and apoptosis of glomerular mesangial cells following pre-treatment of rapamycin post-processing / 实用医学杂志

Objective To investigate the effect of 1,25-dihydroxyvitamin D3 on proliferation and apoptosis of glomerular mesangial cells via the PI3K/Akt/mTOR signal pathway. Methods The normal control group, 1,25-dihydroxyvitamin D3 (10-8 mol/L) group, rapamycin (0.1 μg/mL) group and the rapamycin in combination with 1,25-dihydroxyvitamin D3 group. The cell proliferation was measured by cell counting kit-8 assay. The cell cycle and cell apoptosis were detected by flow cytometry assay , respectively. Results Compared with the normal control group, the proliferation of glomerular mesangial cells was significantly inhibited in the 1 ,25-dihydroxyvitamin D3 group, in the rapamycin group and in the rapamycin in combination with 1,25-dihydroxyvitamin D3 group. The cells at G1 phase were significantly increased, but the cells at S phase were significantly decreased, with significant increase of cell apoptosis rate. Compared with the 1,25-dihydroxyvitamin D3 group, the proliferation of human glomerular mesangial cells was significantly inhibited in the rapamycin group and in the rapamycin in combination with 1,25-dihydroxyvitamin D3 group. Compared with the rapamycin group, the cells at G1 phase were significantly increased and the cells at S phase were significantly decreased in the rapamycin in combination with 1,25-dihydroxyvitamin D3 Group. Conclusions 1,25-dihydroxyvitamin D3 inhibits cell proliferation and promotes human glomerular mesangial cell apoptosis of human glomerular mesangial through the PI3K/Akt/mTOR signal pathway. 1,25-dihydroxyvitamin D3 and rapamycin can synergistically inhibit the proliferation of human glomerular mesangial cells.

Effect of 1,25-dihydroxyvitamin D₃on regulatory T cells in ovariectomized mice / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the correlation between regulatory T (Treg) cells and postmenopausal osteoporosis and the antiosteoporotic effect of 1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃] in relation to Treg cells.</p><p><b>METHODS</b>Fifty female BALB/c mice were randomly divided into five groups: the basal control (BAS), Sham, ovariectomy (OVX), OVX+diethylstilbestrol (OVX+DES), and OVX+1,25(OH)₂D₃. Tibias were harvested and processed with decalcification for quantitative bone histomorphometry. Femurs were stained by immunohistochemistry to detect Foxp3 protein expression. Spleens were used to detect Treg and Foxp3 gene expression by flow cytometry and quantitative RT-PCR, respectively.</p><p><b>RESULTS</b>In comparison with the Sham group, a significant decrease was found in the OVX group in such indices as trabecular bone volume/total tissue area (BV/TV), trabecular number (Tb.N) and trabecular thickness (Tb.Th). 1,25(OH)₂D₃and DES partly prevented the decrease in BV/TV, Tb.N, Tb.Th in OVX mice. Treg cell number, Foxp3 mRNA expression in spleen and Foxp3 protein expression in femur significantly decreased in the OVX-treated group compared with those in the sham group. 1,25(OH)2D₃and DES significantly increased Treg cell number and Foxp3 expression. Treg cells and Foxp3 gene expression were related to bone histomorphometric parameters.</p><p><b>CONCLUSION</b>The decrease in Treg cell numbers is relevant to the postmenopausal osteoporosis. The antiosteoporosis of 1,25(OH)₂D₃is related to regulatory T cells.</p>

Raquitismos hipofosfatémicos hereditarios / Hereditary hypophosphatemic rickets

Los raquitismos hipofosfatémicos hereditarios (RHH) son un grupo de enfermedades caracterizadas por la pérdida renal de fosfatos, que ocasionan retardo del crecimiento, raquitismo y osteomalacia. La forma más común es el raquitismo hipofosfatémico ligado al cromosoma X, el cual es causado por mutaciones inactivantes en el gen PHEX. Las otras formas de los síndromes hipofosfatémicos hereditarios presentan menor prevalencia. Estas incluyen el raquitismo hipofosfatémico autosómico dominante, el raquitismo hipofosfatémico autosómico recesivo tipos 1 y 2 y el raquitismo hipofosfatémico hereditario con hipercalciuria. En este artículo se revisan las bases genéticas de los diferentes tipos de RHH, las manifestaciones clínicas, las características bioquímicas en sangre y orina y los nuevos aspectos de su tratamiento.

Hereditary hypophosphatemic rickets (HHR) are a group of diseases characterized by renal phosphate wasting causing growth retardation, rickets and osteomalacia. The most common form is the X-linked dominant hypophosphatemic rickets caused by inactivating mutations in the PHEX gene. The other hereditary hypophosphatemic syndromes present a lower prevalence. These include autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets types 1 and 2 and the hereditary hypophosphatemic rickets with hypercalciuria. This article reviews the genetic basis of the different types of HHR, clinical manifestations, biochemical characteristics in blood and urine and new aspects of treatment.

Expressions of 1,25 (OH)2D3, vitamin D receptor and 24-hydroxylase in Henoch-Sch(o)nlein purpura / 中华实用儿科临床杂志

Objective To study the expressions of 1,25 (OH) 2 D3,vitamin D receptor (VDR) and 24-hydroxylase (CYP24A1) and investigate the effects of 1,25 (OH)2D3 and its related molecules in the pathogenesis of Henoch-Sch(o)nlein purpura (HSP).Methods 1.The levels in the plasma 1,25 (OH) 2 D3 of 35 HSP patients and 14 healthy children were detected by enzyme-linked immunosorbent assay (ELISA).2.Total RNA of peripheral blood were extracted and transcribed into cDNA.Sybr green dye based real-time quantitative PCR method was used to compare the expression levels (indicated as 2-△ct value) of VDR and CYP24A1 in patients with HSP and those in the controls.Results The level of 1,25 (OH)2D3 was (13.29 ± 10.12) μg/L in plasma of HSP patients,lower than that of the healthy control group[(29.51-± 23.06) μg/L] (P ＜ 0.01).Compared with healthy control group,the level of VDR mRNA was higher but CYP24A1 mRNA was lower in HSP patients (P ＜ 0.05).Conclusion The patients with HSP have lower ability to synthesize active form of vitamin D and respond to VDR-mediated vitamin D effects,enhancing the ability to degrade this hormone.

Effects of 1,25-dihydroxyvitamin D3 on high glucose-induced expression of uncoupling protein 2 and oxidative stress in human renal tubular epithelial cells / 中华内分泌代谢杂志

[Summary] The HK-2 cells with different culture media were divided into normal glucose group (NG group,5.5 mmol/L D-glucose) ; high glucose group (HG group,30 mmol/L D-glucose) ; mannitol group (MG group,5.5mmol/L D-glucose+24.5 mmol/L mannitol) ; 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] groups (V1-V3 group)which were exposed to medium containing 30 mmol/L D-glucose and different concentrations of 1,25-(OH)2D3 ;Nethyl-cysteim control group (NAC group,30 mmoL/L D-glucose + 1.0 mmol/L N-Nethyl-cysteim) ; and ethanol control group(SG group,30 mmol/L D-glucose+6.86 × 10-2 mol/L ethanol).The level of intracellular reactive oxygen species,mitochondrial membrane potential,activity of total-superoxide dismutase (T-SOD),level of malondialdehyde,expression of UCP2 mRNA and protein in HK-2 cells were detected.Compared with NG group,the mitochondrial membrane potential significantly decreased in HG group (P＜0.01),and the mitochondrial membrane potential in V group was lower than that in HG group(P＜0.01).The activity ofT-SOD in HG group was significantly lower than that in NG group(P＜0.01),while its level of malondialdehyde was significantly higher than that in NG group(P＜0.01).Compared with HG group,the activity of T-SOD in V groups was significantly increased (P＜0.05)and the level of malondialdehyde in these groups significantly decreased (P＜0.01).The mRNA expression of UCP2 in HG group was increased significantly in comparison with NG group (P ＜ 0.05) and the expression in V groups was significantly decreased in comparison with HG group (P＜0.01).The results suggest that 1,25-(OH)2D3 could reduce the mitochondrial membrane potential,the production of reactive oxygen species,and regulate the expression of UCP2 in order to suppress the oxidative stress induced by high glucose.

COX-2/PGE2 pathway is involved in 1,25-dihydroxyvitamin D3-induced downregulation of CYP1B1 in breast cancer cell line MCF-7 / 第二军医大学学报

Objective To analyze the expressions of COX-2, p-ERα and CYP1B1 in human breast cancer tissues and ERα positive human breast cancer cell line MCF-7, and to investigate the influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on proliferation, cell cycle transformation, and CYP1B1 protein expression in MCF-7 cells. Methods Immunohistochemical method was applied to examine the expressions of COX-2, p-ERα and CYP1B1 protein in 42 breast cancer tissues, and their association was analyzed. The effects of l,25(OH)2D3 on MCF-7 cell proliferation was investigated by MTT assay and the optimal concentration of l,25(OH)2D3 was determined for the following experiment. The cell cycle was analyzed by flow cytometry and COX-2 mRNA expression in MCF-7 cells was measured by RT-PCR. PGE2 level was detected by ELISA in the culture supernatant. The expression of COX-2, p-ERK, p-ERα and CYP1B1 protein was determined by Western blotting analysis and the distribution of COX-2, p-ERα and CYP1B1 expression in MCF-7 cells was examined by immune cell fluorescence. Results COX-2, p-ERα and CYP1B1 protein were positive in human breast cancer tissues and their expressions were positively correlated with each other(P<0. 05). l,25(OH)2D3 inhibited the proliferation of MCF-7 cells in a time- and dose-dependent manner (P<0. 05). Treatment with 100 nmol/L 1, 25 (OH)2 D3 for 72 h significantly arrested cell cycle in Go/Gi phase (P<0. 05), decreased the expression of COX-2 mRNA in MCF-7 cells (P<0. 05), decreased PGE2 level in the cell culture supernatant (P<0. 01), and down-regulated p-ERK, p-ERα and CYP1B1 protein expression(P<0. 05). Conclusion COX-2/PGE2 pathway plays a positive role in regulating CYP1B1 expression in breast cancer. 1,25(OH)2D3 may inhibit the growth of MCF-7 cells and down-regulate CYP1B1 through COX-2/PGE2 pathway.

Vitamina D: nuevos paradigmas / Vitamin D: New Paradigms

La vitamina D ha pasado de ser solo una vitamina, a ser una importante prohormona con múltiples efectos en diferentes tipos de tejidos y en diversos procesos fisiológicos. Su acción nosolo está relacionada con el metabolismo mineral óseo y el equilibriofosfocálcico, sino también con efectos importantes en múltiplestipos celulares y en diversos mecanismos tales como secreción yefecto de la insulina, función endotelial, regulación del sistema renina-angiotensina-aldosterona, control del ciclo celular y apoptosis,autotolerancia inmunológica, y efectividad de la acción del sistemainmune ante las infecciones, entre muchos otros efectos...

Vitamin D has gone from being just a vitamin, to being an important prohormone with multiple effects on different tissue types and in various physiological processes. Its osolo action is related to the bone mineral metabolism and the equilibriofosfálálco, but also with important effects in multiple cell plots and in diverse mechanisms such as secretion and efecto of the insulin, endothelial function, regulation of the system renin-angiotensina-aldosterona, control of the cellular cycle and apoptosis, immunological self-tolerance, and effectiveness of the immune system's action against infections, among many other effects...