The Role of Vitamin D3 Therapy in Pediatric Bronchiectasis Severity (CF versus non-CF Patients)

Objective: To determine and compare the effect of vitamin D3 supplementation on modifying the disease severity in cystic fibrosis (CF) and non-CF bronchiectasis pediatric patients. Methods: A randomized clinical trial evaluating the role of oral vitamin D3 supplementation for six months, was performed in forty patients with CF and non-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. Results: 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-CF bronchiectasis patients (59.82%) (P = 0.03). Additionally, moderate to severe pulmonary exacerbations significantly decreased by more than 60%, 45% (P = 0.001, 0.005) and frequent exacerbations decreased by 15%, 10% (P = 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 < 0.001). Conclusions: 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-CF bronchiectasis than CF patients.

CYP24A1 inhibition facilitates the anti-tumor effect of vitamin D3 on colorectal cancer cells

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.

Effect of vitamin D3 on production of progesterone in porcine granulosa cells by regulation of steroidogenic enzymes

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.

Vitamin D3 supplementation influences ovarian histomorphometry and follicular development in prepubertal albino rats

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.

Preparation and Spectroscopic of Vanadyl（Ⅱ） Vitamin D3 Amino Acid Mixed Complexes as Insulin Mimetic Drug

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.

A Syndrome of Vitamin D3 Deficiency/Fibromyalgia/Hyperparathyroidism Mimicking Rheumatoid Arthritis, a Clinical Prospective Study

Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

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.

Research Progress on the Roles of Vitamin D3 in Gastrointestinal Cancer

Vitamin D3 is a steroid hormone. Its main functions include regulating calcium and phosphate metabolism, maintaining normal blood calcium levels, regulating bone metabolism, and regulating the physiological functions of many cells. Recent epidemiological studies suggested that vitamin D deficiency correlates with the risk of gastrointestinal cancer and a poor prognosis in cancer patients. Vitamin D3 has demonstrated anti-tumor activities, including reducing tumor cell proliferation, inducing apoptosis, and inducing cell cycle arrest in gastrointestinal cancer. Further studies showed that vitamin D3 can enhance the effects of chemotherapeutic drugs to induce apoptosis and inhibit the proliferation of gastrointestinal cancer cells. Vitamin D3 analogs also exhibit anti-tumor activity, and generally have fewer side effects than vitamin D3. This review describes the molecular characteristics and anti-cancer mechanisms of vitamin D3 and its analogs in gastrointestinal cancer.

花园集团成为世界上最大的VD3生产企业

近日，花园生物科技有限公司——全球最大的维生素D3生产企业。年产500吨维生素D3油剂和2000吨维生素D3饲料添加剂项目正式投产。

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.

Efficacy and safety of vitamin D3 in patients with diabetic nephropathy： a meta-analysis of randomized controlled trials

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.

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.

1,25-Dihydroxyvitamin D3 pretreatment enhances the efficacy of allergen immunotherapy in a mouse allergic asthma model

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.

基于UPLC-MS/MS建立早产儿血清25-(OH)D3和3-epi-25-(OH)D3检测新方法及临床初步应用

目的建立血清25-羟维生素D_(3)[25-hydroxyvitamin D_(3),25-(OH)D_(3)]及3-epi-25-羟维生素D_(3)[3-epi-25-hydroxyvitamin D_(3),3-epi-25-(OH)D_(3)]超高效液相色谱-串联质谱检测新方法(ultra-performance liquid chromatography-tandem mass spectrometry,UPLC-MS/MS),并在早产儿中开展初步应用。方法采用液-液萃取法提取化合物,五氟苯基丙基(pentafluorophenyl propyl,PFPP)色谱柱分离25-(OH)D_(3)与3-epi-25-(OH)D_(3);从最低定量限、线性关系、精密度与准确度等四个方面对新建方法进行验证,并对134例早产儿血清样本进行检测分析。结果25-(OH)D_(3)及3-epi-25-(OH)D_(3)的最低定量限分别为6.05±0.78 nmol/L,1.48±0.20 nmol/L;线性范围3.78~480.00 nmol/L,1.00~128.00 nmol/L;相关系数r2为0.9922,0.9928;25-(OH)D_(3)与3-epi-25-(OH)D_(3)低、中、高浓度质控品的日内精密度和日间精密度均小于15.00%;回收率109.92%,102.25%,98.76%;97.75%,95.25%,99.80%。134例早产儿血清25-(OH)D_(3)平均浓度22.35±13.28nmol/L,3-epi-25-(OH)D_(3)平均浓度5.43±4.35 nmol/L;3-epi-25-(OH)D_(3)占总25-(OH)D_(3)的平均比例为19.96%±12.08%,范围0.00%~60.62%。以25-(OH)D_(3)计算,维生素D(Vitamin D,Vit D)缺乏率、不足率、充足率分别为78.36%,19.40%,2.24%;以总25-(OH)D_(3)计算,Vit D缺乏率、不足率、充足率分别为65.67%,26.12%,8.21%;二者Vit D缺乏率及充足率的比较,差异均有统计学意义(χ^(2)=5.351,1.719,4.823,均P<0.05)。结论本研究建立的UPLC-MS/MS检测法性能良好且能精准检测早产儿血清25-(OH)D_(3)浓度,在早产儿Vit D评估方面具有较好的应用价值。

Effects of testosterone on vitamin D3 and nicotine-induced aortic calcification

Objective To establish a model of vascular calcification in SD rats and observe the role of testosterone in aortic calcification. Methods 10-week-old SD male rats were divided into control group,calcification group,calcifi cation+low-dose testosterone group,calcification+high-dose testosterone group,with 8 rats in each group.

Vitamin D attenuates TGF-β1-induced lung fibroblast proliferation and migration through repression of RasGRP3

Background:Transforming growth factor-β1(TGF-β1)is a pleiotropic cytokine that plays a central role in the pathogenesis of idiopathic pulmonary fibrosis(IPF).While previous studies have revealed a cross-talk between vitamin D and TGF-β1 signaling,it is still unclear how they interact with each other to regulate the progression of IPF.Methods:In this work,we searched for a novel mediator of TGF-β1 activity in lung fibroblasts and examined its regulation by vitamin D.In addition,we investigated the mechanism underlying the interaction between vitamin D and TGF-β1 signaling in lung fibroblast activation.Bioinformatic analysis was performed to identify TGF-β1 downstream target genes.Knockdown and overexpression expression experiments were conducted to determine gene function in the regulation of lung fibroblast proliferation and migration.Results:Analysis of publicly available datasets revealed that RAS guanyl releasing protein 3(RasGRP3)was upregulated in TGF-β1-treated lung fibroblasts and lung tissues from IPF patients relative to healthy controls.Our data confirmed the upregulation of RasGRP3 by TGF-β1 in human MRC5 lung fibroblasts.Overexpression of RasGRP3 enhanced MRC5 cell proliferation and migration.Knockdown of RasGRP3 blocked TGF-β1-induced MRC5 proliferation and migration.Vitamin D abolished TGF-β1-induced RasGRP3 upregulation,which was reversed by inhibition of the vitamin D receptor(VDR).Mechanistically,vitamin D promoted VDR enrichment and prevented mothers against decapentaplegic homolog(SMAD)2 and 3 occupancy at the promoter of RasGRP3.Additionally,overexpression of RasGRP3 reversed the suppressive effect of vitamin D on MRC5 cell proliferation and migration.Conclusion:In conclusion,vitamin D antagonizes TGF-β1-induced lung fibroblast activation by repressing RasGRP3 transcription.

Correlation between 25-hydroxy vitamin D3 level and sudomotor function in patients with type 2 diabetes mellitus

Objective To investigate the relationship between 25-hydroxy vitamin D3[25(OH)D3]level and sudomotor function(SF)in patients with type 2 diabetes mellitus(T2 DM).Methods A total of 1020 patients with T2 DM were collected in this study from Endocrinology Department in Jinling College of Clinical Medicine,Nanjing Medical University during January 2017 to December 2019.

Correlation between Hypovitaminosis D Status and Hyperactivation of IL-6/STAT3 Signaling in Clear Cell Renal Cell Carcinoma

Objective:To analyze serum vitamin D levels in patients with clear cell renal cell carcinoma(ccRCC)by flow cytometry and to investigate the relationship between hypovitaminosis D status and hyperactivation of IL-6/STAT3 signaling in ccRCC.Methods:Eighty patients diagnosed with ccRCC by our oncology department from January 2019 to December 2021 were selected as study subjects,and the control subjects were selected from patients who were receiving health check-up from our hospital(matched according to case group:control group,1:2),with 160 healthy patients.All serum samples collected from the case-control subjects were allowed to stand for 1–2 hours,centrifuged at 3000 rpm for 10 minutes,and stored in a-80°C refrigerator,from which they were removed and thawed to measure 25-hydroxyvitamin D(25(OH)D)and interleukin 6(IL-6)levels.Results:The blood calcium level of patients in the cancer group was significantly lower than that of patients in the non-cancer group,and the difference was statistically significant(P<0.05).The IL-6 level of the cancer group was significantly higher than that of the non-cancer group.In high vitamin D state,the IL-6 level of the non-cancer group was higher than that of the cancer group,and the average concentration of IL-6 in both the cancer group and the non-cancer group was significantly higher in low vitamin D state compared with high vitamin D state(P<0.05);the correlation between hypovitaminosis D status and renal Ki-67 was found to be positive.Conclusion:The results showed that serum IL-6 levels were elevated in the cancer group and circulating serum 25(OH)D levels were negatively correlated with IL-6 levels.In addition,signal transducer and activator of transcription 3(STAT3)signaling in RCC tissues was activated in ccRCC patients and in those with low vitamin D status among the cancer group and was higher than that in those with high vitamin D status.These results suggest that hypovitaminosis D status in ccRCC patients is associated with activated IL-6/STAT3 signaling and the activation of tumor proliferation markers proliferating cell nuclear antigen(PCNA),cyclin D1,and Ki-67.

维生素D_(3)对小鼠支气管哮喘气道炎症和氧化应激反应的作用及其分子机制

目的探究维生素D_(3)(VitD_(3))在小鼠支气管哮喘气道炎症和氧化应激反应中的作用和相关分子机制。方法将28只雌性C57BL/6小鼠随机分为对照组(Ctrl)和模型组。模型组小鼠采用卵清蛋白(OVA)致敏法建立哮喘模型后,将其分为哮喘(Asthma)组、VitD_(3)处理(Asthma+VitD_(3))组和叉头盒O1(FOXO1)抑制剂AS1842856处理(Asthma+AS)组。测定各组小鼠肺阻力(LR)变化。采用ELISA法检测肺泡灌洗液(BALF)中炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β和IL-18的含量。Western blot检测肺组织中FOXO1和NOD样受体热蛋白结构域相关蛋白3(NLRP3)、半胱氨酸天冬氨酸酶-1(Caspase-1)和凋亡斑点蛋白(ASC)的表达水平。结果与Ctrl组相比,Asthma组小鼠的LR升高(P<0.01)。与Asthma组相比,Asthma+VitD_(3)组和Asthma+AS组小鼠的LR降低(P<0.05),Asthma+VitD_(3)组与Asthma+AS组小鼠的LR变化差异无统计学意义。与Ctrl组相比,Asthma组、Asthma+VitD_(3)组和Asthma+AS组小鼠BALF中TNF-α、IL-1β与IL-18含量均增加(P<0.01),肺组织中NLRP3、Caspase-1和ASC蛋白表达水平均升高(P<0.01);与Asthma组相比,Asthma+VitD_(3)组和Asthma+AS组小鼠BALF中上述炎症因子含量均减少(P<0.05),肺组织中NLRP3、FOXO1、Caspase-1和ASC蛋白表达均降低(P<0.05);与Asthma+VitD_(3)组相比,Asthma+AS组中除FOXO1蛋白表达水平升高外(P<0.05),上述其他检测指标差异均无统计学意义。结论VitD_(3)可减轻OVA诱导的小鼠哮喘症状,改善气道炎症程度和降低氧化应激水平,且其机制可能与FOXO1/NLRP3轴的下调有关。

高龄高血压患者血清维生素D3与外周动脉硬化的相关性分析

目的探讨高龄高血压患者血清维生素D3水平与外周动脉硬化的相关性。方法入选2011年9月至2012年11月在北京友谊医院老年科住院的高龄老年高血压患者166例,年龄75~99(85.5±4.9)岁。以血清25-羟基维生素D3[25(OH)D3]<20 ng/ml作为维生素D3缺乏的诊断标准,将患者分为维生素D3缺乏组(n=118)和维生素D3正常组(n=48)。动态血压及下肢动脉超声结果反映外周动脉硬化程度,分析维生素D3缺乏和外周动脉硬化的相关性。采用SPSS 16.0软件对数据进行统计分析。计量资料用均数±标准差(±s)表示,两组比较采用t检验。计数资料用百分率表示,组间比较用χ~2检验。Logistic回归分析下肢动脉狭窄的相关危险因素。结果相比维生素D3水平正常组,维生素D3缺乏组患者的LDL-C水平高,舒张压更低,脉压更大,高脂血症和外周动脉硬化发病率高,差异具有统计学意义(P<0.05)。Logistic回归分析结果表明下肢动脉狭窄与维生素D3水平(OR=0.780,95%CI 0.670~0.890;P=0.039)、舒张压水平负相关(OR=1.030,95%CI 0.929~0.983;P=0.040),而与LDL-C水平正相关(OR=2.446,95%CI 1.138~1.312;P=0·043)。结论高龄高血压患者血清维生素D3缺乏与外周动脉硬化有明显相关性。