1.Study on clinical relationships between gene polymorphism of vitamin D receptor and adiponectin with susceptibility of non-alcohol fatty liver disease
Zhoutao HE ; Canxia XU ; Xiangyang HAN ; Yiyao CHEN ; Yi CHEN
Chongqing Medicine 2017;46(12):1606-1609
Objective To discuss and analyze the clinical relationships between the gene polymorphism of vitamin D receptor and adiponectin with the susceptibility of non-alcohol fatty liver disease(NAFLD).Methods One hundred and two cases of NAFLD were selected as the observation group,and other 100 healthy volunteers were selected as the control group.The gene polymorphism of vitamin D receptor and adiponectin in the two groups was detected,then the genotype distribution and allele frequencies of vitamin D receptor and adiponectin were compared between the two groups,then their relationship with the susceptibility of NAFLD was analyzed.Results The genotype distribution situation of vitamin D receptor BsmI site,adiponectin 45 and 276 sites had statistically significant difference between the observation group and control group(P<0.05).The B allele frequency of BsmI site of vitamin D receptor in the observation group was far lower than that in the control group,and the allele frequencies of 45-T and 276-G of vitamin D receptor in the former were far higher than those in the latter,and the differences between the two groups were statistically significant(P<0.05).The multivariate unconditional Logistic regression analysis showed that vitamin D receptor:bb genotype,adiponectin 45 locus:TT genotype and ALT,TG,complicating hypertension history and HOMA-IR all were the independent risk factors in NAFLD patients.Conclusion The genotype distribution of different sites of vitamin D receptor and adiponectin has obvious abnormality in the patients with NAFLD,and both are closely related with the NAFLD susceptibility.
2.Expression and significance of ecto-5'-nucleotidase in colon tissue of Crohn's disease mice
SU Peiqiang ; ZHONG Zhuangxia ; CHEN Yiyao ; CHEN Chaochao ; HE Zhoutao ; LAN Cheng
China Tropical Medicine 2023;23(10):1071-
Abstract: Objective This study aimed to investigate the expression of CD73 in colonic tissues in Crohn's disease (CD) and its significance and possible mechanism of action. Methods Thirty male BALB/c mice were randomly divided into normal control group, model group and intervention group. The control group was fed normally, and the model group was treated with TNBS+40% alcohol enema to establish a mouse model of Crohn's disease induced by chronic inflammation. The intervention group was treated with AB-680 intraperitoneally on the second day of each enema based on the model group. Mice body weight, fecal traits and fecal occult blood were recorded for disease activity index (DAI) score of inflammatory bowel disease. The animals were sacrificed at 7th week, their colonic tissues were removed, weighed and measured. The tissue inflammation was observed by standard hematoxylin-eosin (HE) staining. Masson staining was used to measure the area of collagen in colon tissue of mice. CD73 was detected by fluorescence quantitative PCR and immunohistochemistry. The expression levels of TGF-β, TNF-α and IL-6 in colon tissue of mice were determined by ELISA. Results The DAI score was (0.10±0.16) in the control group, (2.80±0.79) in the model group, and (3.07±0.34) in the intervention group. Compared with the control group, the DAI scores of the model and intervention groups were increased significantly (P<0.05). Compared with the model group, the DAI score of the intervention group was significantly increased (P<0.05). HE staining showed that there was no inflammation in the colon of the control group, while the colon of the model group and the intervention group showed typical inflammatory manifestations such as edema and congestion, inflammatory cell infiltration, and mucosal ulcer. The area ratio of collagen in the control group was (4.95±0.82)%, in the model group was (24.62±1.46)%, and in the intervention group was (54.47±2.75)%. Compared with the control group, the area ratio of collagen in the model group and the intervention group was significantly increased (P<0.05). Compared with the model group, the area ratio of collagen in the intervention group was significantly increased (P<0.05). Compared with the control group, the expression of CD73 in colon tissue of the model group and the intervention group was significantly increased (P<0.05). Compared with the model group, the expression of CD73 in colon tissue of the intervention group was decreased (P<0.05). Compared with the control group, the expressions of TGF-β, TNF-α and IL-6 in the model group and the intervention group were significantly increased (P<0.05). Compared with the model group, the expression of TGF-β, TNF-α and IL-6 in the intervention group decreased (P<0.05). Conclusions CD73 is upregulated in colon tissue of CD mice, it can inhibit inflammatory reaction and improve fibrosis by up-regulating TGF-β expression. On the other hand, CD73 can aggravate the inflammatory response in CD intestinal inflammation and fibrosis by up-regulating the expression of IL-6 and TNF-α. Therefore, CD73 may play a bidirectional regulatory role in intestinal inflammation and fibrosis of CD.
3.Effect of GLP-1 on liver function and TLR4/NF-κB signal pathway in NAFLD rats
Yiyao CHEN ; Yi CHEN ; Zhoutao HE ; Manni CAI
The Journal of Practical Medicine 2018;34(1):26-29
Objective To study the effect of GLP-1 on the liver function and the signal pathway of TLR4/NF-κB in NAFLD rats.Methods Forty-five rats were randomly divided into two groups,15 with normal diet fed and 30 with high-fat diet,so as to form NAFLD model.In the tenth week,28 rats fed with high-fat diet were randomly divided into two groups,the model control group (14) and the GLP-1 intervention group (14 rats).The normal diet fed in 15 rats served as the normal control group.After the model group and the control group rats were injected with saline treatment,the intervention group rats were injected with liraglutide treatment.We observed the changes in the activity of rats,body weight,appetite,urine and other conditions.Results Compared with the control group,the liver index,liver mass,ALT,AST,TG and TC of the model rats were significantly higher than those of the control group (P < 0.05).The liver index,liver mass,ALT,AST,TG and TC of the model rats were significant lower in the GLP-1 intervention group than those in the model control group (P < 0.05).Compared with the normal control group,the expression of TLR4 and NF-κB protein in the model control group increased in the model control group (P < 0.05).Compared with the model control group,the expression of TLR4 and NF-κB protein was decreased in the GLP-1 intervention group (P < 0.05).Conclusion GLP-1 can significantly reverse the disorder of glucose and lipid metabolism and impaired liver function in NAFLD rats,and GLP-1 can significantly reduce the expression of NF-κB and TLR4 protein in the liver tissues of rats.
4.Expression of obesity-related gene and forkhead transcription factors in liver of nonalcoholic fatty liver disease rat model
Yiyao CHEN ; Yi CHEN ; Zhoutao HE ; Manni CAI
Chongqing Medicine 2017;46(30):4185-4186,4189
Objective To research the obesity-related gene (FTO) and forkhead transcription factors O1 (FoxO1) protein expression level in the livers of non-alcoholic fatty liver disease(NAFLD) rat model. Methods The animal model of NAFLD in rats was prepared by feeding high energy and high fat feed. Then the rat blood and liver tissue were collected for detecting the liver index and blood biochemical indexes, including triglycerides (TG), total cholesterol (TC), alanine aminotransferase (AST), aspartate aminotransferase(ALT) ,alkaline phosphatase(ALP),high-density lipoprotein (HDL) and low density lipoprotein(LDL) ;the liver pathological examination was performed;FTO protein and Fox O1 protein expression levels in rat liver were detected by using the immunohistochemical assay. Results The rat liver weight,body weight and liver index after 8 weeks in the model group were higher than those in the control group,the difference was statistically significant (P<0.05);the levels of AST, ALT, LDL, ALP, TG and TC in the model group were higher than those in the control group,the difference was statistically significant (P<0. 05),the HDL level in the model group was lower than that in the control group, the difference was statistically significant (P<0.05) ;the model group produced steatosis and inflammation in hepatic lobule part,while the control group had no these lesions;the FTO prot ein and FoxO1 protein expression levels in liver of the model group were higher than those in the control group,the difference was statistically significant (P<0.05). Conclusion FTO and FoxO1 interaction may disturb the normal energy and fat metabolism.
5.Expression of IFN-γ and IL-10 in peripheral blood and intestinal mucosa of patients with diarrhea post-infectious irritable bowel syndrome
Zhoutao HE ; Xiaoning SUN ; Xuchun ZHOU ; Baili HUANG ; Yiyao CHEN ; Taozhi DENG ; Xiangyang HAN ; Cheng LAN
Chongqing Medicine 2018;47(4):433-435
Objective To investigate the expression change of cytokines in peripheral blood and intestinal mucosa in the patients with diarrhea post-infectious irritable bowel syndrome(PI-IBS) and its relation with clinical symptoms scores.Methods Thirty outpatients and inpatients with diarrhea PI-IBS(observation group) and contemporaneous 30 individuals undergoing physical examination(control group) in the Hainan Provincial People's Hospital from January to December 2013 were selected.The peripheral blood mononuclear cells(PBMC) were separated and cultured.Then the levels of IFN-y and IL-10 in peripheral blood and cell culture supernatant fluid were detected by ELISA.The colonic mucosal tissue was taken by coloscopy.Then colonic mucosal IFN-γ and IL-10 protein expression was detected by immunohistochemistry staining.Furthermore,the correlationship between the level change of IFN-γ and IL-10 with clinical symptom score was analyzed by using the Spearman correlation method.Results Peripheral blod IL-10 and IFN-γ levels had no statistical difference between the two groups(P>0.05).Compared with the control group,in PBMC seperation and cuture,the IFN-γ level in the observation group was increased and IL-10 level was decreased,the difference was statistically signifieant(P<0.01).The intestinal main symptom score in the observation group had the positive correlation with IFN-γ expression level of PBMC culture supernatant fluid and colonic mucosal IFN-γ expression level(r=0.45,0.94,P<0.01),and had the negative correlation with IL-10 expression level(r=-0.52,-0.79,P<0.01).Conclusion The unbalance of IFN-γ and IL-10 level could be involved in the pathogenesis of diarrhea PI-IBS,which can serve as the observation indicators of disease activity.
6. Difference of left ventricular segmental longitudinal strain in patients with lymphoma receiving anthracycline detected by three dimensional speckle tracking imaging
Yuchen XU ; Chujie ZHANG ; Rui ZHAO ; Yiyao HE ; Qunling ZHANG ; Xianhong SHU ; Leilei CHENG
Chinese Journal of Ultrasonography 2018;27(6):467-472
Objective:
To detect the changes of systolic function of left ventricle in patients with lymphoma receiving anthracycline by three dimensional speckle tracking imaging(3D-STI).
Methods:
Thirty patients with newly diagnosed diffused large B-cell lymphoma who had received R-CHOP chemotherapy were enrolled. Left ventricular global longitudinal strain (GLS), global circumferential strain(GCS) and longitudinal strain(LS) on different left ventricular segments were measured by 3D-STI at baseline, after the completion of 2 cycles and 4 cycles of the regimen respectively.
Results:
Compared with baseline, GLS reduced significantly after four cycles of anthracycline chemotherapy(
7.Histological features of tumor-bearing tissues formed by human fibroblasts after reprograming by Piwil2.
Guangping ZENG ; ; Xin WU ; Dawei HE ; Yiyao FU ; Xing LIU ; Deying ZHANG ; Tao LIN ; Guanghui WEI
Chinese Journal of Oncology 2015;37(8):565-572
OBJECTIVETo observe the histological features of tumor-bearing tissues formed by human fibroblasts after reprograming by spermatogonial stem cell self-renewal key regulating gene Piwil2 (Piwil2-iCSC).
METHODSPiwil2-iCSC tumor spheroids-like colonies were selected for tumor formation assay in four nude mice. Pathological features of Piwil2-iCSC tumors were observed by histology. Stem cell markers and common triploblastic markers were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) assay and immunohistochemistry. Germ cell tumor markers were detected by immunohistochemical examination.
RESULTSTwo weeks after inoculation, subcutaneous tumors were formed in all the four nude mice with a tumor formation rate of 100%. In the Piwil2-iCSC tumor tissues, Piwil2-GFP(+) cells showed high-density nuclear expression and were widely observed in DAPI-stained sections. Numerous mitotic figure of the neoplastic cells were seen (>10 cells/field of vision under high magnification) in HE-stained sections. Enlarged abnormal cell nuclei were observed. RT-PCR assay showed that Piwil2-iCSC tumors still expressed Piwil2 and some self-renewal and pluripotent markers of stem cells and some markers of triploblastic differentiation. Immunohistochemical staining showed that the tumors expressed stem cell markers, triploblastic markers and germ cell tumor markers AFP and HCG.
CONCLUSIONSPiwil2-iCSC tumors are probably undifferentiated embryonic small cell carcinoma, most likely to be immature teratoma, mixed with yolk sac tumor and choriocarcinoma components. It can be used as a useful model for the research of origin or genesis mechanism of cancer stem cells and the treatment of relevant tumors.
Adult Stem Cells ; Animals ; Argonaute Proteins ; genetics ; Cellular Reprogramming Techniques ; Choriocarcinoma ; pathology ; Endodermal Sinus Tumor ; pathology ; Fibroblasts ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Mice ; Mice, Nude ; Neoplasms, Germ Cell and Embryonal ; chemistry ; genetics ; pathology ; Neoplastic Stem Cells ; chemistry ; pathology ; Real-Time Polymerase Chain Reaction ; Spheroids, Cellular ; Teratoma ; pathology ; Time Factors
8.Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner.
Cancan ZHENG ; Xiaomei YU ; Yiyao LIANG ; Yidong ZHU ; Yan HE ; Long LIAO ; Dingkang WANG ; Yanming YANG ; Xingfeng YIN ; Ang LI ; Qingyu HE ; Bin LI
Acta Pharmaceutica Sinica B 2022;12(3):1271-1287
As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease.
9.Biallelic variants in RBM42 cause a multisystem disorder with neurological, facial, cardiac, and musculoskeletal involvement.
Yiyao CHEN ; Bingxin YANG ; Xiaoyu Merlin ZHANG ; Songchang CHEN ; Minhui WANG ; Liya HU ; Nina PAN ; Shuyuan LI ; Weihui SHI ; Zhenhua YANG ; Li WANG ; Yajing TAN ; Jian WANG ; Yanlin WANG ; Qinghe XING ; Zhonghua MA ; Jinsong LI ; He-Feng HUANG ; Jinglan ZHANG ; Chenming XU
Protein & Cell 2024;15(1):52-68
Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female
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Animals
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Mice
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Humans
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Child, Preschool
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Intellectual Disability/genetics*
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Heart Defects, Congenital/genetics*
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Facies
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Cleft Palate
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Muscle Hypotonia