Colonic vitamin D receptor expression is inversely associated with disease activity and jumonji domain-containing 3 in active ulcerative colitis

BACKGROUND The expression of jumonji domain-containing 3(Jmjd3)and trimethylated H3 lysine 27(H3K27me3)in active ulcerative colitis(UC)and the correlation between vitamin D receptor(VDR)and the Jmjd3 pathway are unknown.AIM To study the relationship between VDR,Jmjd3 and H3K27me3 in patients with active UC.METHODS One hundred patients with active UC and 56 healthy controls were enrolled in this study.The patients with active UC were divided into groups according to mild(n=29),moderate(n=32)and severe(n=29)disease activity based on the modified Mayo score.Vitamin D levels were measured by radioimmunoassay.Colonic mucosal tissues from UC patients and controls were collected by colonoscopy.The expression of VDR,Jmjd3 and H3K27me3 in the intestinal mucosa was determined by immunohistochemistry staining.RESULTS Patients with active UC had lower levels of serum vitamin D(13.7±2.8 ng/mL,P<0.001)than the controls(16.2±2.5 ng/mL).In the UC cohort,serum vitamin D level was negatively correlated with disease activity(r=-0.323,P=0.001).VDR expression in the mucosa of UC patients was reduced compared to that in normal tissues(P<0.001)and negatively correlated with disease activity(r=-0.868,P<0.001).Similar results for VDR expression were noted in the most serious lesion(defined as UC diseased)and 20 cm proximal to the anus(defined as UC normal)(P<0.05).Simultaneously,Jmjd3 expression significantly increased in UC patients(P<0.001),but no difference was found between the different sites in UC patients.H3K27me3 expression in UC patients was significantly down-regulated when compared with normal tissues(P<0.001),but up-regulated in the mild disease activity group in comparison with the moderate disease activity group of UC patients(P<0.05).Jmjd3 Level was negatively correlated with the level of VDR(r=-0.342,P=0.002)and H3K27me3(r=-0.341,P=0.002),while VDR level was positively correlated with H3K27me3(r=0.473,P<0.001).CONCLUSION Serum vitamin D and VDR were inversely correlated with disease activity in active UC.Jmjd3 expression increased in the colonic mucosa of active UC patients and was negatively associated with VDR and H3K27me3 level.

Curative efficacy of vitamin D3 in combination with tripterygium wilfordii polyglycoside in patients with rheumatoid arthritis and its influences on indices of bone restoration

Objective: To investigate the curative efficacy of vitamin D3 in combination with tripterygium wilfordii polyglycoside in patients with rheumatoid arthritis (RA) and its influences on indices of bone restoration. Methods: A total of 320 patients with RA were collected as observation objects to be randomly divided into the control group and the observation group with 160 cases in each group. The control group was given treatment of tripterygium wilfordii polyglycoside, while the observation group was given treatment of vitamin D3 in combination with tripterygium wilfordii polyglycoside. All patients received a course treatment with 3 months. The curative efficacy, improvement of joint symptoms, changes of laboratory tests, indices of bone restoration and adverse reactions were compared. Results: After 3 months, assessment of curative efficacy showed that the observation group had a total curative efficiency ratio of 90.6%, which was significantly higher than that of 81.2% in the control group. Among the indices which reflect the improvement of joint symptoms, the joint pain index, joint tenderness index and joint swollenness index were statistically reduced in the observation group than those in the control group. And after treatment, in comparison with the control group, indices of laboratory tests of rheumatoid factor (RF), antistreptolyisn O antibody (ASO), c-reactive protein (CRP) were statistically lower respectively in the observation group. As to indices of bone restoration after treatment, the observation group had statistically lower serum level of receptor activator of nf-kb ligand (RNKL) and higher level of osteoprotegerin (OPG) than those in the control group. During the treatment, incidences of adverse reactions in the control group and the observation group were statistically same. Conclusion: Vitamin D3 in combination with tripterygium wilfordii polyglycoside has well curative efficacy in patients with RA, which can significantly improve joint symptoms, indices of laboratory tests and bone restoration.

Vitamin D₃Receptor Activation Rescued Corticostriatal Neural Activity and Improved Motor Function in –D₂R Tardive Dyskinesia Mice Model

Haloperidol-induced dyskinesia has been linked to a reduction in dopamine activity characterized by the inhibition of dopamine receptive sites on D2-receptor (D2R). As a result of D2R inhibition, calcium-linked neural activity is affected and seen as a decline in mo-tor-cognitive function after prolonged haloperidol use in the treatment of psychotic disorders. In this study, we have elucidated the relationship between haloperidol-induced tardive dyskinesia and the neural activity in motor cortex (M1), basal nucleus (CPu), prefrontal cortex (PFC) and hippocampus (CA1). Also, we explored the role of Vitamin D3 receptor (VD3R) activation as a therapeutic target in improving motor-cognitive functions in dyskinetic mice. Dyskinesia was induced in adult BALB/c mice after 28 days of haloperidol treatment (10 mg/Kg;intraperitoneal). We established the presence of abnormal involuntary movements (AIMs) in the haloperidol treated mice (-D2) through assessment of the threshold and amplitude of abnormal involuntary movements (AIMs) for the Limbs (Li) and Orolingual (Ol) area (Li and Ol AIMs). As a confirmatory test, the dyskinetic mice (-D2) showed high global AIMs score when compared with the VD3RA intervention group (-D2/+VDR) for Li and Ol AIMs. Furthermore, in the behavioral tests, the dyskinetic mice exhibited a decrease in latency of fall (LOF;Rotarod-P 2/+VDR), 100 mg/Kg for 7 days, CPu-CA1 burst activity was restored leading to a decrease in abnormal movement, and an increase in motor function. Ultimately, we deduced that VD3RA activation reduced the threshold of abnormal movement in haloperidol induced dyskinesia.

维生素D3通过增强肝组织维生素D受体活性阻断JAK/STAT3通路减轻高胆固醇血症小鼠幽门螺杆菌感染相关胃炎

目的 探讨维生素D3(VD3)能否通过降低血脂抑制Janus激酶/信号转导子与转录激活子3(JAK/STAT3)信号通路从而减轻幽门螺杆菌(Hp)感染。方法 建立高胆固醇小鼠模型和Hp感染小鼠模型,采用VD3灌胃8周。采用实时定量PCR检测小鼠肝组织维生素D受体(VDR)、胰岛素诱导基因2(Insig-2)及小鼠胃组织胃泌素的mRNA表达,Western blot法检测胃组织JAK、STAT3、环加氧酶2(COX2)蛋白的表达,生化分析法检测小鼠血清胆固醇水平,ELISA检测各组小鼠血清白细胞介素6(IL-6)及IL-8水平,HE染色小鼠肝组织及胃组织的病变情况。结果 高胆固醇组及高胆固醇联合Hp感染组小鼠在灌胃VD3后,小鼠肝组织VDR、Insig-2的水平明显上升,胃泌素水平表达降低;胃组织JAK、STAT3及COX2蛋白的表达降低,血清中胆固醇水平降低,IL-6水平无明显变化,IL-8水平降低;与对照组相比,高胆固醇联合Hp感染组肝细胞气球样变减少,胃组织炎症减轻,胆固醇组、Hp感染组胃组织炎症也减轻。结论 VD3通过增强肝组织VDR的活性,阻断JAK/STAT3信号通路,抑制炎症因子表达减轻胃炎的程度。

活性维生素D_3加钙剂治疗妇女骨质疏松症2年疗效观察

目的评价活性维生素Ｄ３（ＡＶＤ３）加钙剂方案治疗华南地区绝经后妇女骨质疏松症的疗效。方法９６例患者配伍分成３组，一组用ＡＶＤ３加钙剂连续治疗６个疗程，共２４个月，服钙剂和不治疗两组作对照。结果ＡＶＤ３加钙剂方案显著减少骨质疏松患者骨质丢失，２５．０％患者全身骨密度、２８．１％髋部骨密度及５３．１％腰椎骨密度增加，解除患者疼痛，减少骨折发生率。结论该方案对多数患者是有效的、无明显毒副反应。

活性维生素D3对UUO模型大鼠P38MAPK信号通路的影响

目的探讨活性维生素D 3对单侧输尿管梗阻(UUO)大鼠肾间质纤维化的影响及其机制。方法54只雄性SD大鼠随机分为UUO模型组、假手术组、活性维生素D 3干预组,其中36只SD大鼠建立UUO模型,活性维生素D 3干预组在建模起给予活性维生素D 30.5μg/d灌胃,分别于术后3、7、14 d各处死6只大鼠,免疫组化观察肾小管间质损害程度;Western印迹法检测P38MAPK及磷酸化P38MAPK蛋白表达量。结果与假手术组相比,UUO模型组磷酸化P38MAPK蛋白表达量随时间延长显著增加(P<0.01);活性维生素D 3干预组7 d、14 d磷酸化P38MAPK蛋白表达量较UUO模型组表达显著减少(P<0.05);P38MAPK蛋白表达量各组差异无统计学意义。结论活性维生素D 3抑制UUO大鼠肾组织中P38MAPK信号通路的激活,延缓肾间质纤维化。

维生素D联合硫酸镁对重症毛细支气管炎患儿JAK/STAT信号通路与25(OH)D水平的影响

目的探讨维生素D联合硫酸镁对重症毛细支气管炎患儿Janus激酶/信号转导和转录激活因子(JAK/STAT)信号通路与25-羟维生素D_(3)[25-(OH)D_(3)]水平的影响。方法选取2021年2月至2022年2月沧州市人民医院收治的重症毛细支气管炎患儿93例作为研究对象,开展前瞻性研究,采用随机数字表法分为实验组(n=46)和对照组(n=47)。对照组采取硫酸镁治疗,实验组采取维生素D联合硫酸镁治疗。治疗2周后,观察并对比两组患儿临床疗效、临床症状消失时间,治疗前后血氧分压、经皮血氧饱和度、呼吸窘迫评分、JAK/STAT信号通路与25-(OH)D_(3)水平变化。结果实验组患儿治疗总有效率为95.65%明显高于对照组(78.72%),差异有统计学意义(P<0.05)。实验组患儿肺部炎症吸收时间、肺部湿啰音消失时间、咳嗽消失时间均早于对照组,差异均有统计学意义(P<0.05)。治疗2周后,两组患儿动脉血氧分析及经皮血氧饱和度明显高于治疗前,呼吸窘迫评分体系评分低于治疗前,且实验组患儿动脉血氧分析及经皮血氧饱和度为(8.25±1.24)kPa、(97.51±4.86)%,明显高于对照组[(7.14±1.15)kPa、(88.24±5.79)%],呼吸窘迫评分体系评分为(3.29±0.67)分,低于对照组[(5.37±0.85)分],差异均有统计学意义(P<0.05)。治疗2周后,两组患儿JAK2、STAT1、STAT2表达均高于治疗前,且实验组患儿JAK2、STAT1、STAT2表达为0.59±0.11、0.51±0.15、0.62±0.16,均高于对照组(0.42±0.10、0.38±0.12、0.43±0.17),差异均有统计学意义(P<0.05)。治疗2周后,两组患儿免疫球蛋白(Ig)A、25-(OH)D_(3)、IgG水平明显高于治疗前,且实验组患儿IgA、25-(OH)D_(3)、IgG水平为(2.21±0.27)g/L、(62.59±7.69)ng/L、(9.89±1.47)g/L,明显高于对照组[(1.79±0.32)g/L、(45.42±7.21)ng/L、(8.52±1.86)g/L],差异均有统计学意义(P<0.05)。两组不良反应情况相比,差异无统计学意义(P>0.05)。结论维生素D联合硫酸镁用于重症毛细支气管炎患儿治疗后,能明显改善患儿临床症状,提高临床治疗效率,还能通过上调JAK/STAT信号通路及25-(OH)D_(3)水平,加强患儿机体免疫应答,可为临床重症毛细支气管炎治疗提供新思路。

活性维生素D_3加钙剂对绝经后骨质疏松症患者骨代谢生化指标的影响

目的 观察活性维生素D3 加钙剂对绝经后骨质疏松症患者血Ca、P、ALP和尿Ca/Cr、尿HYP/Cr及跟骨骨密度 (BMD)的影响 ,评价活性维生素D3 加钙剂对绝经后骨质疏松症的治疗作用。方法 活性维生素D30 .2 5 μg ,每天 2次 ;钙尔奇 1粒 ,每天 1次 ,连用 4个月 ,于用药前后测定血Ca、P、ALP和尿Ca/Cr、尿HYP/Cr,并测定跟骨BMD。结果 用药后血Ca升高 ,血ALP、尿Ca/Cr、尿HYP/Cr明显下降 ,跟骨BMD增加。结论 活性维生素D3

维生素D缺乏和慢性肝脏疾病

在人类，维生素D（vitamin D，VD）主要是在紫外线照射下在皮肤合成，合成的VD3尚不具有生物活性，需要和VD转运蛋白或白蛋白结合运输到肝脏和肾脏进行两步羟化，最后形成具有生物活性的骨化三醇[1,25（OH）2D3]。在肝脏合成的25（OH）D代表循环中主要的VD代谢产物，也是明确人类VD状态最可靠的参数[1]。