1.Associativity of hsa_circ_0001588 level with TLR4 and T lymphocyte subsets in plasma of patients with gastric cancer
Huiting XU ; Feng WANG ; Bingyan CHEN ; Jian WANG ; Chenyun HE
Immunological Journal 2024;40(1):80-86
To explore the level of hsa_circ_0001588 in plasma of patients with gastric cancer and to analyze the relationship between the plasma level of hsa_circ_0001588 and clinical characteristic,toll like receptors 4(TLR4)and T lymphocyte subsets,this study enrolled 124 gastric cancer patients who were treated in our hospital from March 2021 to May 2022 as study group.Simultaneously,another 130 patients diagnosed with superficial gastritis by gastroscopy were selected as benign group,and 130 healthy individuals were set as control group.The plasma hsa_circ_0001588 level was measured by quantitative real-time polymerase chain reaction,the plasma level of TLR4 was detected by double antibody sandwich ELISA,and plasma CD3+,CD4+,CD8+,and CD4+/CD8+levels were tested by Wmini5146 flow cytometry.Then the diagnostic efficacy of plasma hsa_circ_0001588,TLR4 and T lymphocytes for gastric cancer was evaluated,and the correlation between the level of hsa_circ_0001588 in plasma and the level of TLR4 and T lymphocytes in gastric cancer patients was verified.Data showed that the levels of hsa_circ_0001588,TLR4 and CD8+in plasma of study group were higher than those of benign group and control group,while the levels of CD3+,CD4+and CD4+/CD8+were lower than those of benign group and control group(P<0.05).Furthermore,a decrease was observed in plasma hsa_circ_0001588 level in gastric cancer patients after surgery compared to baseline data.Among gastric cancer patients of different clinicopathological characteristics,patients with high clinical stage,high degree of infiltration,poor differentiation and distant metastasis had high plasma hsa_circ_0001588 level(P<0.05).Diagnostic analysis denoted that the separate test of plasma hsa_circ_0001588,TLR4 and T-lymphocytes all had good diagnostic efficacy for gastric cancer,while combined test showed the highest diagnostic efficacy.Comparison among gastric cancer patients revealed that high hsa_circ_0001588 expression group had lower expression of CD3+,CD4+and CD4+/CD8+,and higher expression of TLR4 and CD8+than those of low hsa_circ_0001588 expression group(P<0.05),suggesting that plasma hsa_circ_0001588 level was negatively correlated with CD3+,CD4+and CD4+/CD8+expression,but positively correlated with TLR4 and CD8+.In conclusion,the level of hsa_circ_0001588 in plasma is elevated in patients with gastric cancer,and it has a negative correlation with CD3+,CD4+and CD4+/CD8+,but positive correlation with TLR4 and CD8+expression.
2.Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus.
Lijie WEI ; Yi JIANG ; Peng GAO ; Jingyi ZHANG ; Xuan ZHOU ; Shenglan ZHU ; Yuting CHEN ; Huiting ZHANG ; Yuanyuan DU ; Chenyun FANG ; Jiaqi LI ; Xuan GAO ; Mengzhou HE ; Shaoshuai WANG ; Ling FENG ; Jun YU
Journal of Zhejiang University. Science. B 2023;24(1):78-88
Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.
Female
;
Humans
;
Pregnancy
;
Blood Glucose/metabolism*
;
Diabetes, Gestational/metabolism*
;
Glucose/metabolism*
;
Melatonin/metabolism*
;
Polymorphism, Genetic
;
PPAR gamma
;
Receptor, Melatonin, MT2/genetics*