Enhanced Response of Acute Monocytic Leukemia Cells to Low-dose Cytarabine by 1,25-dihydroxyvitamin D3

Low-dose cytarabine combined with differentiating or DNA hypomethylating agents,such as vitamin D compounds,is a potential regimen to treat acute myeloid leukemia(AML)patients who are unfit for high-intensity chemotherapy.The present study aimed to determine which subset of AML would be most responsive to low-dose cytarabine with the differentiating agent 1,25-dihydroxyvitamin D3(1,25-D3).Here,firstly,c Bio Portal database was used and we found out that vitamin D receptor(VDR)was highly expressed in acute monocytic leukemia(M5)and high VDR expression was associated with a poor survival of AML patients.Then,we confirmed that 1,25-D3 at clinical available concentration could induce more significant differentiation in acute monocytic leukemia cell lines(U937,MOLM-13,THP-1)and blasts from M5 patients than in non-monocytic cell lines(KG1 a and K562)and blasts from M2 patient.Finally,it was shown that the combination of 1,25-D3 and low-dose cytarabine further increased the differentiating rate,growth inhibition and G0/G1 arrest,while mild changes were found in the apoptosis in acute monocytic leukemia cell lines.Our study demonstrates that the enhanced response of acute monocytic leukemia cells to low-dose cytarabine by 1,25-D3 might indicate a novel therapeutic direction for patients with acute monocytic leukemia,especially for elderly and frail ones.

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 tilled 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 arc 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.

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

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.

银屑病患者1,25(OH)_(2)D_(3)与炎性因子水平关系及阿维A联合NB-UVB疗效观察

目的 探讨银屑病患者血清1,25-二羟基维生素D_(3)[1,25(OH)_(2)D_(3)]与炎性因子水平关系及阿维A联合窄谱中波紫外线(NB-UVB)方案的疗效。方法 选取2020年1月至2021年11月在山西省运城市中心医院治疗的银屑病患者109例作为观察组,同时选取100名健康者作为对照组,根据病历号末尾奇偶数将观察组患者分为观察A组(n=57)和观察B组(n=52),其中观察A组给予阿维A联合NB-UVB治疗,观察B组给予NB-UVB治疗,对比观察两组治疗疗效。结果 观察组血清1,25(OH)_(2)D_(3)明显低于对照组,差异有统计学意义(t=-16.614,P<0.05),而白细胞计数(WBC)、中性粒细胞/淋巴细胞比(NLR)、血小板/淋巴细胞比(PLR)、C反应蛋白(CRP)和肿瘤坏死因子a(TNF-a)明显高于对照组,差异有统计学意义(t=12.832、5.869、8.678、26.944、19.084,P<0.05)。观察组中重度患者血清1,25(OH)_(2)D_(3)明显低于轻度患者,差异有统计学意义(t=2.699,P<0.05),而NLR和PLR明显高于轻度患者,差异有统计学意义(t=-5.141、-3.719,P<0.05)。结论 银屑病患者血清1,25(OH)_(2)D_(3)与NLR和PLR呈负相关,同时与患者病情程度呈负相关;阿维A联合NB-UVB治疗银屑病有较好的疗效,明显改善患者生活质量。

1,25-Dihydroxyvitamin D_(3) effects on the regulation of the insulin receptor gene in the hind limb muscle and heart of streptozotocin-induced diabetic rats

In the present study, we examine the effects of the treatment with 1,25-dihydroxyvitamin D3 [150 IU/Kg (3.75 μg/Kg) once a day, for 15 days] to non-diabetic and streptozotocin-induced diabetic rats. The results indicate that treatment with 1,25-dihydroxyvitamin D3 had minor effects in non-diabetic rats. The same treatment in streptozotocin-induced diabetic rats, although it did not correct the hyperglycemia and hypoinsulinemia induced by the diabetes, caused other actions that could mean beneficial effects on the amelioration of diabetes e.g., it avoided body weight loss, increased calcium and phosphorus plasma levels, and corrected the over-expression of the insulin receptor mRNA species of 9.5 and 7.5 Kb present in the hind limb muscle and heart of these animals. These genomic 1,25-dihydroxyvitamin D3 effects could involve transcriptional mechanisms of repression mediated by vitamin D response elements in the rat insulin receptor gene promoter. Using computer analysis of this promoter, we propose the -249/-235 bp VDRE (5’GGGTGACCCGGGGTT3’) with a pyrimidine (T) in the (+7) position of the3’half-site as the best candidate for negative control by 1,25-dihydroxy-vitamin D3. In addition, posttranscriptional mechanisms of regulation could also be implicated. Thus, computer inspection of the5’untranslated region of the rat insulin receptor pre-mRNA indicated the presence of a virtual internal ribosome entry segment whereas the computer inspection of the3’untranslated region localized various destabilizing sequences, including various AU-rich elements. We propose that through these virtual cis-regulatory sequences, 1,25-dihydroxyvitamin D3 could control the translation and stability of insulin receptor mRNA species in the hind limb muscle and heart of diabetic rats.

血清1,25-二羟维生素D3和超敏C反应蛋白联合检测在早期Ⅱ型糖尿病肾病中的诊断价值研究

目的探讨血清1,25-二羟维生素D3与超敏C反应蛋白(hypersensitive C-reactive protein,hs-CRP)联合检测对早期Ⅱ型糖尿病肾病的诊断价值。方法选取2015年6月至2017年6月我院住院的T2DM患者及同期健康体检者作为研究对象。通过检测24h尿蛋白排泄率(urinary albumin excretion rate,UAER),从而将所有病例分为3组:对照(Control)组,单纯糖尿病组(simple diabetes,SD组),早期糖尿病肾病组(early diabetic nephropathy,EDN组)。分别测量各组身高、体重、收缩压和舒张压。使用全自动生化分析仪分别检测各组总胆固醇(TC)、甘油三酯(TG)、血肌酐(Scr)以及血尿酸(UA)含量。同时,分别检测各组血清中hs-CRP和1,25-二羟维生素D3水平。结果结果表明,各组间基线均衡一致,可比性较好。同时,与Control组比较,SD组和EDN组血清1,25-二羟维生素D3含量降低,而hs-CRP含量增加(P<0.05)。与SD组比较,EDN组血清1,25-二羟维生素D3含量降低,但是hs-CRP表达增加(P<0.05)。结果表明,hs-CRP和血清1,25-二羟维生素D3呈负相关(r=-0.37,P<0.05)。结论血清1,25-二羟维生素D3和hs-CRP联合检测有利于糖尿病肾病组(diabetic nephropathy,DN)病情严重程度的判断。

Correlation between expression of 1 α-hydroxylase and hypocalcaemia in rats with severe pancreatitis

Objective:To investigate the essential biochemical indices like 1-hydroxylase and hypocalcaemia in the rats with severe acute pancreatitis and explore the correlation between them.Methods:A total of 120 SPF grade Wistar male rats which were in similar physiological status were selected and randomly divided into two groups:sham group(SO group) and severe acute pancreatitis group(SAP group).Then they were divided into 1 h,3 h,6 h,and 12 h subgroups according to the killing lime.The severe acute pancreatitis model was established by retrograde injection of 5%sodium taurocholate.Serum calcium,serum creatinine,serum urea nitrogen and serum amylase were measured at different time.Serum 1,25 dihydroxy vitamin D3 level was determined by enzyme linked immunosorbentassay.The expression of 1-hydroxylase protein in the kidney tissue was determined with Western blotting and immunohistochemistry to observe its location.The pathologic features of the kidney tissue section was observed under light microscope and submicroscopic structure of the proximal convoluted tubule epithelial cell was observed under transmission electron microscope.Results:Compared with the SO group,rats in the SAP group showed continuous pathological injury as time went by.There was significant increase in serum creatinine,serum urea nitrogen and serum amylase in SAP group compared with the SO group 1,3,6,12 hours after the operation(P<0.05).There was significant decrease in serum calcium and 1,25 dihydroxy vitamin D3 3.6,12 hours after the operation(P<0.05).It also showed that the expression of the 1-hydroxylase protein in kidney tissues was upregulated at 1 h.3 h and decreased at 6h,12 h compared with the SO group.The serum calcium,1,25 dihydroxy vitamin D3 and the expression of the 1-hydroxylase protein in kidney tissues of the SAP group showed sustaining decrease.Western blotting showed positive correlation between the 1-hydroxylase expression and serum calcium at 3 h.6 h and 12 h(r=0.976,P<0.001;r=0.948.P<0.001;r=0.742,P=0.001) and also positive correlation between the 1-hydroxylase expression and serum1,25 dihydroxy vitamin D3 at 1 h,3 h,6 h and 12 h(r=0.935,P<0.001;r=0.952,P<0.001;r=0.917.P<0.001:r=0.874,P<0.001).Conclusions:At the early stage of the kidney injury,the expression of 1-hydroxylase in the kidney tissue is reduced with the progress of the disease and the decrease in its activity has a correlation with the hypocalcaemia.

南京汉族人群维生素D结合蛋白受体基因多态性与2型糖尿病的相关性研究

目的探讨南京汉族人群中维生素D结合蛋白(DBP)受体基因Asp416Glu与Thr420Lys多态性与2型糖尿病及血清1,25-二羟基维生素D3[1,25(OH)2D3]的相关性。方法采用聚合酶链反应限制性片段长度多态性(PCR-R FLP)技术,检测105例2型糖尿病患者和105例正常者的DBP基因型,用酶联免疫吸附(Elisa)法测定血清1,25(OH)2D3水平,并检测相关临床及生化指标,比较DBP基因型和等位基因频率的分布差异及不同基因型血清1,25(OH)2D3等相关指标的差异。结果维生素D结合蛋白受体基因Asp416Glu与Thr420Lys多态性位点基因型和等位基因频率在两组中的分布无显著性差异(P>0.05)。血清1,25(OH)2D3在不同基因型间无有意义的差别(P>0.05)。结论 DBP受体基因Asp416Glu与Thr420Lys多态性与2型糖尿病及血清1,25(OH)2D3无关。

Effects of T-2 Toxin Exposure on Bone Metabolism and Bone Development of Mice

T-2 toxin is the most widespread mycotoxin in crops,feed and food,which poses a serious threat to body health.Bone is the main target tissue for T-2 toxin accumulation.Ingestion of food contaminated by T-2 toxin is the main cause of Kashin-Beck disease.However,the specific mechanism of bone damage caused by T-2 toxin is still unclear.In this study,a total of 40 male C57BL/6N mice were divided into four groups and orally treated with 0,0.5,1.0 and 2.0 mg·kg^(-1) body weight T-2 toxin for 28 days.The results showed that exposure to T-2 toxin led to weight loss,bone mineral density reduction and femoral structural damage of mice.In addition,osteoblast-mediated bone formation was inhibited,and osteoclast-mediated bone resorption was enhanced.Meanwhile,the levels of bone metabolism-related hormones including parathyroid hormone,calcitonin and 1,25-dihydroxyvitamin D3 were reduced.More importantly,it was found that the level of neuropeptide Y(a neurohormone)was decreased.These results provided a new perspetive for understanding the osteotoxicity of T-2 toxin.

Evaluation of Serum Vitamin D Concentration and Blood Eosinophil and Basophil Counts in Patients With Vitiligo:A Cross-sectional Study From Rafsanjan and Zarand,Iran

Objective:Vitiligo is a chronic autoimmune depigmenting skin disorder.In this disease,the destruction of functional melanocytes can lead to reduced or absent pigmentation of the skin.Vitamin D deficiency has been reported in some autoimmune diseases.The association of eosinophils and basophils with autoimmune diseases has also been recently examined.The present study was performed to evaluate the serum vitamin D concentration and blood eosinophil and basophil counts in patients with vitiligo.Methods:Data from 30 patients aged 20 to 40 years with vitiligo and 30 healthy people were collected.Blood samples were obtained to evaluate the serum vitamin D concentration,and eosinophil and basophil counts.The serum vitamin D concentration was measured by enzyme-linked immunosorbent assay.Independent t-test was used to compare the quantitative variables between the groups.Results:This descriptive cross-sectional study involved 30 patients with vitiligo.The average serum vitamin D concentration was significantly lower in the case group than in the control group(P=0.01).Furthermore,the mean serum vitamin D concentration was significantly lower in women than in men(P=0.03).The average eosinophil and basophil counts were not significantly different between the case and control groups.Discussion:The results of this study showed that the serum vitamin D concentration is low in patients with vitiligo.However,whether this reduction is a factor in the promotion of vitiligo or occurs after the onset of vitiligo remains unknown.Further studies on the serum vitamin D concentration in patients with vitiligo are needed to clarity this issue and develop effective treatments.

Correlation between tear fluid and serum vitamin D levels

Background:Vitamin D deficiency is associated with a range of systemic diseases including ocular disorders.The objective of this study is to measure tear vitamin D levels and investigate the correlation between serum and tear vitamin D levels.Methods:A total of 48 healthy volunteers without any systemic and ocular disease were recruited for this observational cohort study.Serum was collected using clot activator coated Vacutainer®Plus tubes.Tear fluid was collected using Schirmer’s strips.Serum and tear total 25-hydroxyvitamin D levels were measured by competitive chemiluminescent ELISA and the correlation between the levels were studied.Results:The measured serum 25-hydroxyvitamin D level ranged between 3.3 and 27.5 ng/ml(Mean±SEM,9.4±0.7 ng/ml;Median 8.4 ng/ml).Significantly(p<0.0001)higher level of 25-hydroxyvitamin D was detected in the tears(Mean±SEM,17.0±1.6 ng/ml;Range 3.2–45.8 ng/ml;Median,16.3 ng/ml)compared to serum.An average of~2 fold(Mean±SEM,1.9±0.2;Range 0.4–5.8;Median,1.7)higher 25-hydroxyvitamin D was observed in tears compared to serum in the subjects.In addition,a positive correlation was observed between serum and tear 25-hydroxyvitamin D levels(r=0.5595;p<0.0001).Conclusions:A higher level of 25-hydroxyvitamin D was observed in the tear fluid compared to that of the serum.It would be beneficial to consider tear vitamin D levels to study its role with reference to ocular surface diseases.