1.Research progress on polymorphism of vitamin D and its receptor gene and susceptibility to bone tuberculosis.
Xin-Feng LIU ; Yan-Jun ZHANG ; Jun-Jie LI ; Jun YANG ; Hong-Jing TIAN
China Journal of Orthopaedics and Traumatology 2025;38(2):211-216
Bone tuberculosis is one of the main lesions of extrapulmonary tuberculosis, and the affected site shows local pain and limited movement, and the severe patients face a higher risk of teratogenicity and disability. Especially in the context of the increasing spread of multidrug-resistant tuberculosis, it is particularly urgent to seek innovative treatment options. In recent years, vitamin D plays an important role in the prevention and treatment of bone tuberculosis, and the mechanism of action has been continuously explored. At the same time, vitamin D receptor gene polymorphism has also been found to be closely related to the susceptibility and risk of bone tuberculosis. This article reviewed the relationship between vitamin D and its receptor gene polymorphisms and the susceptibility to bone tuberculosis. It was found that vitamin D deficiency increased the susceptibility to bone tuberculosis in both adults and children, and multiple genotypes of vitamin D receptor had an effect on the susceptibility to bone tuberculosis, especially FokⅠ genotype. It may also be one of the reasons for the increase in the number of bone tuberculosis. Through the study of the relationship between vitamin D and its receptor gene polymorphism and the susceptibility to bone tuberculosis, some factors inducing bone tuberculosis can be avoided, and related new drugs can be more targeted, such as vitamin D supplements, gene receptor related antagonists, etc. To provide more systematic and targeted strategies for the prevention and treatment of bone tuberculosis.
Humans
;
Receptors, Calcitriol/genetics*
;
Genetic Predisposition to Disease
;
Polymorphism, Genetic
;
Vitamin D/metabolism*
;
Tuberculosis, Osteoarticular/metabolism*
2.Clinicopathological significance and prognostic value of serum 25-hydroxyvitamin D3 level in children with IgA vasculitis nephritis.
Pao YU ; Pei ZHANG ; Chun-Lin GAO ; Zi WANG ; Yin ZHANG ; Zheng GE ; Bi ZHOU
Chinese Journal of Contemporary Pediatrics 2025;27(1):55-61
OBJECTIVES:
To study the significance of serum 25-hydroxyvitamin D3 [25-(OH)D3] level in the clinicopathological characteristics and prognosis of children with immunoglobulin A vasculitis nephritis (IgAVN).
METHODS:
A retrospective analysis was conducted on the clinical data of children with IgAVN who underwent renal biopsy at Suzhou Hospital Affiliated to Anhui Medical University and Jinling Hospital of the Medical School of Nanjing University from June 2015 to June 2020. Based on serum 25-(OH)D3 level, the patients were divided into a normal group and a lower group. The clinicopathological characteristics and follow-up data of the two groups were collected and compared.
RESULTS:
A total of 359 children with IgAVN were included. Compared to the normal group (62 cases), the lower group (297 cases) exhibited higher incidences of hematochezia and gross hematuria, higher levels of serum creatinine, blood urea nitrogen, urinary retinol protein, urinary N-acetyl-β-D-glucosaminidase, and quantitative urinary protein, and a longer duration from renal biopsy to urinary protein becoming negative, as well as lower estimated glomerular filtration rate and albumin level (P<0.05). Renal pathology in the lower group showed a higher occurrence of tubular interstitial injury, crescent formation, segmental sclerosis in glomeruli, and inflammatory cell infiltration in the renal interstitium compared to the normal group (P<0.05). Survival analysis indicated that the cumulative renal survival rate was lower in the lower group (P<0.05). Multivariate Cox regression analysis revealed that low serum 25-(OH)D3 level is an independent risk factor for poor prognosis in children with IgAVN.
CONCLUSIONS
Children with IgAVN and low serum 25-(OH)D3 level have relatively severe clinicopathological manifestations. Low serum 25-(OH)D3 level is an independent risk factor for poor prognosis in children with IgAVN.
Humans
;
Male
;
Female
;
Child
;
Prognosis
;
Retrospective Studies
;
Calcifediol/blood*
;
Child, Preschool
;
Adolescent
;
Glomerulonephritis, IGA/mortality*
;
Vasculitis/pathology*
;
IgA Vasculitis/mortality*
3.Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation.
Hang ZHAO ; Xin MA ; Hao WANG ; Xiao-Jie DING ; Le KUAI ; Jian-Kun SONG ; Zhan ZHANG ; Dan YANG ; Chun-Jie GAO ; Bin LI ; Mi ZHOU
Journal of Integrative Medicine 2025;23(3):309-319
OBJECTIVE:
To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD).
METHODS:
The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4+ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis.
RESULTS:
POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA.
CONCLUSION
Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy*
;
Animals
;
Humans
;
Cell Differentiation/drug effects*
;
Phosphorylation/drug effects*
;
Mice
;
Th2 Cells/drug effects*
;
Keratinocytes/drug effects*
;
Disease Models, Animal
;
Mice, Inbred BALB C
;
Calcitriol/analogs & derivatives*
4.Expression and Significance of Vitamin D Receptor Gene and NF-κB Pathway in Blood of Children with Acute Lymphoblastic Leukemia.
Paerhati YILISUYA ; Nuriding HAILIQIGULI ; Mei YAN
Journal of Experimental Hematology 2023;31(6):1624-1628
OBJECTIVE:
To investigate the expression, clinical significance and prognosis of vitamin D receptor (VDR) gene and NF-κB pathway in children with acute lymphoblastic leukemia (ALL).
METHODS:
Thirty children with definitive diagnoses of ALL from December 2018 to December 2021 were selected as ALL group, and 30 healthy children under physical examination were selected as control group. Peripheral blood of all study subjects was collected. The VDR and NF-κB mRNA and protein expressions were detected by real-time quantitative PCR and Western blot, respectively. The relationship between mRNA expression of the above genes and clinical characteristics of children was retrospectively analyzed.
RESULTS:
The relative expression of VDR mRNA in peripheral blood of children with ALL was significantly lower than that in the control group (P < 0.05), while NF-κB mRNA was higher (P < 0.001). The expression of NF-κB mRNA in ALL children with peripheral blood white blood cell count (WBC) < 50×109/L at initial diagnosis was significantly higher than those with WBC≥50×109/L (P < 0.01). The expression of NF-κB mRNA in ALL children with infection was significantly higher than that those without infection (P < 0.05). There were no significant differences in NF-κB mRNA expression between children with different sex, age, hemoglobin at initial diagnosis, platelet, immunologic typing, risk and induced response (P >0.05).
CONCLUSION
The expression of NF-κB is of value to diagnosis and prognosis of ALL in children.
Child
;
Humans
;
NF-kappa B
;
Receptors, Calcitriol/genetics*
;
Retrospective Studies
;
Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
;
RNA, Messenger/genetics*
5.Correlation between 25-hydroxyvitamin D and nephroblastoma in children and its value in assessing disease prognosis.
Li ZHAO ; Xu-Kai MA ; Yu LIU ; Ying-Bin YUE ; Mei YAN
Chinese Journal of Contemporary Pediatrics 2023;25(5):483-488
OBJECTIVES:
To study the correlation between 25-hydroxyvitamin D [25-(OH)D] and nephroblastoma in children and its value in assessing the prognosis of the disease.
METHODS:
A total of 50 children with nephroblastoma who were admitted from January 2018 to December 2022 were included as the nephroblastoma group, and according to the postoperative pathological type, they were divided into a good prognosis group with 38 children and a poor prognosis group with 12 children. A total of 50 healthy children who underwent physical examination during the same period of time served as the healthy control group. The above groups were compared in terms of serum creatinine and 25-(OH)D level. A Spearman correlation analysis was used to investigate the correlation between serum 25-(OH)D level and therapeutic effect reaction. A multivariate logistic regression analysis was used to identify the risk factors affecting the prognosis of nephroblastoma in children.
RESULTS:
The nephroblastoma group had significantly lower levels of serum creatinine and 25-(OH)D than the healthy control group (P<0.05). Compared with the good prognosis group, the poor prognosis group had a significantly larger tumor diameter, a significantly higher proportion of children with stage III-IV tumors, a significantly higher rate of tumor metastasis, and significantly lower serum levels of creatinine and 25-(OH)D (P<0.05). The Spearman correlation analysis showed that serum 25-(OH)D level was negatively correlated with therapeutic effect reaction (rs=-0.685, P<0.001). The multivariate logistic regression analysis showed that tumor diameter ≥10 cm, stage III-IV tumors, presence of tumor metastasis, and 25-(OH)D <19 ng/mL were closely associated with the poor prognosis of nephroblastoma in children (P<0.05). Serum 25-(OH)D level had an area under the curve of 0.805 (95%CI: 0.706-0.903, P<0.001) in evaluating the prognosis of nephroblastoma in children, with a Youden index of 0.512, a sensitivity of 0.938, and a specificity of 0.575 at the optimal cut-off value of 1.764 ng/mL.
CONCLUSIONS
There is a significant correlation between 25-(OH)D level and the prognosis of nephroblastoma in children, and 25-(OH)D can be used for prognosis prediction.
Humans
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Child
;
Creatinine
;
Vitamin D Deficiency/complications*
;
Vitamin D
;
Calcifediol
;
Prognosis
;
Wilms Tumor
;
Kidney Neoplasms/complications*
6.Vitamin D receptor (VDR) mediates the quiescence of activated hepatic stellate cells (aHSCs) by regulating M2 macrophage exosomal smooth muscle cell-associated protein 5 (SMAP-5).
Xuwentai LIU ; Yue WU ; Yanyi LI ; Kaiming LI ; Siyuan HOU ; Ming DING ; Jingmin TAN ; Zijing ZHU ; Yingqi TANG ; Yuming LIU ; Qianhui SUN ; Cong WANG ; Can ZHANG
Journal of Zhejiang University. Science. B 2023;24(3):248-261
An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.
Humans
;
Hepatic Stellate Cells/pathology*
;
Receptors, Calcitriol
;
Liver Cirrhosis/pathology*
;
Macrophages/metabolism*
7.Interactions of Vitamin D Receptor Polymorphisms with Hypertriglyceridemia and Obesity in Chinese Individuals Susceptible to Hypertension and Diabetes Comorbidity.
Hua Lei SUN ; Tong ZHAO ; Dong Dong ZHANG ; Ming Ming FENG ; Ze XU ; Hao Yue HUANG ; Luo Ya ZHANG ; Wen Jie LI ; Xing LI ; Jia Yu DUAN ; Jia LI
Biomedical and Environmental Sciences 2023;36(2):196-200
9.Polymorphisms of the Vitamin D Receptor Gene and Sex-Differential Associations with Lipid Profiles in Chinese Han Adults.
Yan Mei CHEN ; Ping XU ; Zhou Tian WANG ; Yu Mei ZHU ; Chun Mei GONG ; Chang Hua HUANG ; Xiao Li LIU ; Ji Chang ZHOU
Biomedical and Environmental Sciences 2022;35(2):115-125
OBJECTIVE:
To explore the association of single nucleotide polymorphisms (SNPs) of the vitamin D receptor gene ( VDR) with circulating lipids considering gender differences.
METHODS:
Of the Han Chinese adults recruited from a health examination center for inclusion in the study, the circulating lipids, 25-hydroxyvitamin D (25OHD), and other parameters were measured. The VDR SNPs of Cdx2 (rs11568820), Fok1 (rs2228570), Apa1 (rs7975232), and Taq1 (rs731236) were genotyped with a qPCR test using blood DNA samples, and their associations with lipids were analyzed using logistic regression.
RESULTS:
In the female participants ( n = 236 with dyslipidemia and 888 without dyslipidemia), multiple genotype models of Fok1 indicated a positive correlation of B (not A) alleles with LDLC level ( P < 0.05). In the male participants ( n = 299 with dyslipidemia and 564 without dyslipidemia), the recessive model of Cdx2 and the additive and recessive models of Fok1 differed ( P < 0.05) between the HDLC-classified subgroups, respectively, and Fok1 BB and Cdx2 TT presented interactions with 25OHD in the negative associations with HDLC ( P < 0.05).
CONCLUSION
In the Chinese Han adults included in the study, the Fok1 B-allele of VDR was associated with higher LDLC in females, and the Fok1 B-allele and the Cdx2 T-allele of VDR were associated with lower HDLC in males. The interaction of VD and Fok1 BB or Cdx2 TT in males synergistically decreased HDLC levels.
Adult
;
Alleles
;
Asians/genetics*
;
China/ethnology*
;
Dyslipidemias/genetics*
;
Female
;
Genetic Predisposition to Disease/genetics*
;
Genotype
;
Humans
;
Lipids/blood*
;
Male
;
Middle Aged
;
Polymorphism, Single Nucleotide
;
Receptors, Calcitriol/genetics*
;
Sex Factors
;
Vitamin D/blood*
10.Levels of fat-soluble vitamins A, D, and E and their influencing factors in children with obesity.
Rui-Ping LIU ; Yang CHEN ; Hai-Bin WU ; Feng-Mei XIONG ; Fang-Yuan HE ; Yuan-Yuan LI
Chinese Journal of Contemporary Pediatrics 2022;24(5):572-578
OBJECTIVES:
To investigate the levels of fat-soluble vitamins A, D, and E in children with obesity and their influencing factors.
METHODS:
A total of 273 children with obesity who attended the Department of Clinical Nutrition, Xi'an Children's Hospital, from January 2019 to April 2021 were enrolled as the obesity group. A total of 226 children with normal body weight who underwent physical examination during the same period were enrolled as the control group. Anthropometric parameters and body composition were measured for both groups, and the serum concentrations of vitamins A, D, and E were also measured.
RESULTS:
Compared with the control group, the obesity group had significantly higher serum levels of vitamin A [(1.32±0.21) μmol/L vs (1.16±0.21) μmol/L, P<0.001] and vitamin E [(9.3±1.4) mg/L vs (8.3±1.2) mg/L, P<0.001] and a significant reduction in the level of 25-hydroxyvitamin D [(49±22) nmol/L vs (62±24) nmol/L, P<0.001]. In the obesity group, the prevalence rates of marginal vitamin A deficiency, vitamin D deficiency/insufficiency, and vitamin E insufficiency were 5.5% (15/273), 56.8% (155/273), and 4.0% (11/273), respectively. After adjustment for body mass index Z-score and waist-to-height ratio, serum vitamin A level was positively correlated with age (P<0.001), while vitamins E and 25-hydroxyvitamin D levels were negatively correlated with age in children with obesity (P<0.001). After adjustment for age, the serum levels of vitamin A, vitamin E and 25-hydroxyvitamin D were not correlated with degree of obesity, percentage of body fat, and duration of obesity in children with obesity, while the serum levels of vitamins A and E were positively correlated with waist-to-height ratio (P<0.001).
CONCLUSIONS
There are higher serum levels of vitamins A and E in children with obesity, especially in those with abdominal obesity, while serum vitamin D nutritional status is poor and worsens with age. Therefore, vitamin D nutritional status should be taken seriously for children with obesity, and vitamin D supplementation should be performed when necessary.
Calcifediol
;
Child
;
Humans
;
Pediatric Obesity
;
Vitamin A
;
Vitamin D
;
Vitamin E
;
Vitamins

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