Ulnar-Mammary syndrome with TBX3 gene mutation in a Chinese family: A case report and literature review / 中南大学学报(医学版)

Ulnar-Mammary syndrome (UMS) is a rare monogenic disorder caused by mutations of the TBX3 gene. This paper reported a family of UMS. The proband, a 15-year old man, was presented with mammary gland dysplasia, ulnar limb defect, short stature, and delayed growth. Whole exome sequencing revealed a 1294_1301dup mutation in exon 6 of the TBX3 gene. Sanger sequencing was used to verify other members of the family, which suggested his mother also carried the same mutation, but merely resulting in the dysplasia of her left little finger. Notably, unilateral finger involvement without any systemic organ involvement was unusual in UMS patients. The proband then was treated with recombinant human growth hormone (rhGH) and human chorionic gonadotropin (hCG). After a year and a half, his height and secondary sexual characteristics were significantly improved. The clinical manifestations of the disease are highly heterogeneous, which is easy to be misdiagnosed and missed. When the diagnosis is unclear, genetic testing is helpful for auxiliary diagnosis.

Inhibitory effect of miR-3195 on the proliferation of human laryngeal carcinoma Hep-2 cells and its mechanism / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effect of miR-3195 on the proliferation of laryngeal carcinoma Hep-2 cells and its molecular mechanism. Methods: From January 2008 to August 2012, the laryngeal cancer tissues and their corresponding paracancerous tissues from 29 patients with laryngeal cancer who were admitted to the Department of Otorhinolaryngology, Chenzhou First People's Hospital Affiliated to teaching hospital of University of South China were selected for this study. qPCR was used to detect the expression of miR-3195 in laryngeal carcinoma and the paracancerous tissues; Hep-2 cell line with stable and high expression of miR-3195 was constructed. The proliferation of miR-3195 over-expressed Hep-2 cells and the control cells was observed by MTT method. A nude mouse xenograft model was established to observe the proliferation of miR-3195 overexpressed Hep-2 cells in nude mice. Bioinformatics tools were used to predict the target gene of miR-3195; the luciferase vector of TBX1 3'UTR was constructed, and its luciferase activity was examined with dual luciferase detection system; Western blotting was used to detect the TBX1 protein expression in miR-3195 over-expressed cells and control cells. Results: The expression of miR-3195 in laryngeal carcinoma tissues was significantly lower than that in paracancerous tissues (P<0.01); miR-3195 up-regulation could inhibit the proliferation of Hep-2 cells (P<0.01) and significantly inhibit the growth of transplanted tumors in nude mice (P<0.05); The results of the Dual luciferase reporter gene assay indicated that miR-3195 might targetedly bind to TBX1 (P<0.05), and Western blotting proved that miR-3195 could inhibit the expression of TBX1 protein (P<0.05). Conclusion: miR-3195 has a significant inhibitory effect on the proliferation of Hep-2 cells, and its molecular mechanism may be related to the negative regulation of TBX1 expression.

Research progress on mechanism of TBX1 gene affecting phenotype of 22q11.2 microdeletion syndrome / 医学研究生学报

22q11.2 microdeletion syndrome is a genetic syndrome caused by the deletion of 22q11.21-q11.23 in the proximal long arm microfragment of chromosome 22 for human. TBX1 belongs to the T-box family and is located in 22q11.2 of chromosome. Studies have shown that haploinsufficiency of TBX1 is the main cause of 22q11.2 microdeletion syndrome, which is of great significance for the appearance of its phenotype. Therefore, this paper reviews the research progress of TBX1 in the mechanism of cardiac disease, pulmonary artery phenotype, thymus development, pharyngeal and palatal development, lymphatic formation, and low proliferation of parathyroid tumors.

Research progress on mechanism of TBX1 gene affecting phenotype of 22q11.2 microdeletion syndrome / 医学研究生学报

22q11.2 microdeletion syndrome is a genetic syndrome caused by the deletion of 22q11.21-q11.23 in the proximal long arm microfragment of chromosome 22 for human. TBX1 belongs to the T-box family and is located in 22q11.2 of chromosome. Studies have shown that haploinsufficiency of TBX1 is the main cause of 22q11.2 microdeletion syndrome, which is of great significance for the appearance of its phenotype. Therefore, this paper reviews the research progress of TBX1 in the mechanism of cardiac disease, pulmonary artery phenotype, thymus development, pharyngeal and palatal development, lymphatic formation, and low proliferation of parathyroid tumors.

Abnormal expression of TBX4 during anorectal development in rat embryos with ethylenethiourea-induced anorectal malformations

BACKGROUND: To assess the expression of T-box transcription factor 4 (TBX4) during the anorectal development in normal and ethylenethiourea (ETU)-induced anorectal malformations (ARM) rat embryos. METHODS: Anorectal malformations was induced by ETU on the 10th gestational day (E10) in rat embryos. Spatiotemporal expression of TBX4 was evaluated in normal (n = 490) and ETU-induced ARM rat embryos (n = 455) from E13 to E16 by immunohistochemical staining, Western blot analysis and real-time RT-PCR. RESULTS: In the normal embryos, immunohistochemical staining revealed that TBX4 expression was detected in the epithelium of hindgut and urorectal septum (URS) on E13. TBX4-immunopositive cells were increased significantly in the epithelium of hindgut and URS, the future anal orifice part of cloacal membrane on E14. On E15, abundant stained cells were observed in the rectum, URS and dorsal cloacal membrane and the expression of positive cells reached its peak. On E16, only sporadic positive cells were distributed in the epithelium of the distal rectum. In the ARM embryos, the hindgut/rectum, URS and dorsal cloacal membrane were faint for TBX4 immunohistochemical staining. In the normal group, TBX4 protein and mRNA expression showed time-dependent changes in the hindgut/rectum from E13 to E16 on Western blot and real-time RT-PCR. On E13 and E15, the expression level of TBX4 mRNA in the ARM group was significantly lower than that in the normal group (P < 0.05). On E15, the expression level of TBX4 protein in the ARM group was significantly lower than that in the normal group (P < 0.05). CONCLUSIONS: The expression of TBX4 was downregulated in ETU-induced ARM embryos, which may play important roles in the pathogenesis of anorectal development.

Association of single nucleotide polymorphisms of TBX5 gene and environmental exposure index with susceptibility to oral cancer / 中华预防医学杂志

Objective@#To explore the association of TBX5 polymorphisms and environmental exposure index with susceptibility to oral cancer.@*Methods@#A case-control study was conducted to collect 300 oral cancer patients hospitalized in the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University from September 2010 to December 2016. A total of 445 non-tumor patients were selected as the control group. Questionnaires were used to collect the information of all subjects and 5 ml peripheral blood was collected to detect single nucleotide polymorphisms (SNPs) of the rs10492336 locus of TBX5 gene. According to the environmental exposure index score, subjects were divided into two groups, low risk group (0-2.31) and high risk group (2.32-11.76). To analyze the association of TBX5 gene rs10492336 SNPs, environmental exposure index and oral cancer and its interactions.@*Results@#The age of all subjects in the case group and control group were (56.19±13.10) years and (54.56±12.48) years old. Compared with CC genotype, the OR (95%CI) values of the co-dominant genetic model AC genotype and the dominant genetic model AC+AA genotype were 0.69 (0.49-0.98) and 0.70 (0.51-0.97), respectively. Compared with the low risk group, the OR (95%CI) risk of oral cancer in the high risk group was 3.72 (2.55-5.43). The results of gene-environment interaction analysis showed that compared with the group with CC genotype and high risk of environmental exposure index, the OR (95%CI) value of oral cancer in the group with AC+AA genotype and low risk of environmental exposure index was 0.18(0.10-0.31). Furthermore there was a multiplicative interaction between rs10492336 SNPs and environmental exposure index (β=-0.405, P<0.001).@*Conclusion@#This study suggests that the TBX5 gene rs10492336 SNPs and environmental exposure index were associated with oral cancer. And there was a multiplication interaction between rs10492336 SNPs and environmental exposure index.

Analysis of the correlation between severe pneumonia and inflammatory factors and TBX21 locus rs16947078 / 中国基层医药

Objective@#To analyze the correlation between severe pneumonia and inflammatory factors and TBX21 locus rs16947078.@*Methods@#From March 2017 to March 2019, in the Fourth People's Hospital of Wenling, 71 patients with severe pneumonia were selected, and 83 patients with general pneumonia were selected during the same period.The levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-18 (IL-18) and tumor necrosis factor-alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The genotype and gene distribution of rs16947078 at TBX21 locus were detected by real-time fluorescence quantitative PCR.@*Results@#The score of CPIS in the severe pneumonia group was higher than that in the common pneumonia group [(6.57±1.20)points and (4.93±1.05)points] (t=9.045, P<0.05). The serum levels of IL-6 [(65.42±13.25)ng/L], IL-8 [(457.87±45.36)ng/L], IL-18 [(87.59±15.46)ng/L] and TNF-α[(58.98±13.25)ng/L] in the severe pneumonia group were higher than those in the general pneumonia group [(36.71±8.98)ng/L, (218.98±32.45)ng/L, (54.37±12.10)ng/L and (37.54±7.90)ng/L] (t=15.926, 37.959, 14.946, 12.394, all P<0.05). The G distribution of rs16947078 allele at TBX21 locus in the severe pneumonia group (40.85%) was higher than that in the normal pneumonia group (18.07%) (χ2=9.724, P<0.05). The GG (36.62%) of TBX21 locus rs16947078 in the severe pneumonia group was higher than that in the common pneumonia group (12.05%), while the AA (52.11%) of TBX21 locus in the severe pneumonia group was lower than that in the common pneumonia group (72.29%) (χ2=12.898, 6.682, P<0.05).@*Conclusion@#The levels of inflammatory factors IL-6, IL-8, IL-18 and TNF-α in patients with severe pneumonia aresignificantly increased, and the TBX21 locus rs16947078 allele A may be a susceptible gene for severe pneumonia.

Role of over-expression of TBX3 and TBX18 in the enrichment and differentiation of human induced pluripotent stem cells into sinoatrial node-like cells / 中国修复重建外科杂志

Objective : To explore the role of over-expression of TBX3 and TBX18 in inducing human induced pluripotent stem cells (HiPS) to enrich and differentiate into sinoatrial node-like cells. Methods: The expression of stemness markers OCT3/4, SOX2, and NANOG in HiPS was detected by real-time fluorescence quantitative PCR (qRT- PCR), and compared with human embryonic stem cells (hESCs). Immunofluorescence staining was used to observe the expression of HiPS stemness markers OCT3/4, NANOG, SSEA4, and TRA-1-60. The HiPS were directional differentiated into cardiomyocytes, the expressions of ISL1, NK2 homeobox 5 (NKX2-5), ACTN1, and TNNT2 were detected by qRT-PCR, and human adult cardiomyocytes (hACM) were used as positive control. Immunofluorescence staining was used to observe the expressions of NKX2-5, cardiac troponin (cTnT), α-actinin, atria myosin light chain 2A (MLC-2A), and ventricular myosin light chain 2V (MLC-2V). The positive rate of α-actinin was detected by flow cytometry. On the 3rd day after HiPS were differentiated into cardiomyocytes (mesodermal stage), lentiviral over-expressions of sinoatrial node-related genes TBX3 and TBX18 were carried out for 21 days. The relative expressions of specific markers TBX3, TBX18, SHOX2, NKX2-5, HCN4, and HCN1 in sinoatrial node cells were detected by qRT-PCR, and compared with enhanced green fluorescent protein blank virus. Results : OCT3/4, SOX2, and NANOG were highly expressed in HiPS and ESCs, and there was no significant difference in the relative expression of each gene ( P>0.05); OCT3/4 and NANOG were specifically distributed in the nucleus of HiPS, while SSEA4 and TRA-1-60 were distributed in the cell membrane. The relative expressions of ISL1 gene at 5, 7, 21, and 28 days and NKX2-5 gene at 7, 21, and 28 days of HiPS differentiation into cardiomyocytes were significantly higher than those of hACM ( P0.05). There was no significant difference in the relative expression of each gene between the over-expressed TBX18 group and the control group ( P>0.05). Conclusion: HiPS and hESCs have similar pluripotency, and we have established a stable method for maintaining and culturing the stemness of HiPS. A technological platform for the efficient differentiation of HiPS into cardiomyocytes has been successfully established. Although TBX3 and TBX18 do not play a significant role in promoting the enrichment and differentiation of HiPS into sinoatrial node-like cells, TBX3 shows a certain promoting trend, which can be further explored in the future.

Advances in the mechanism of Tbx2 regulation in embryonic cardiac development / 国际儿科学杂志

Embryonic cardiogenesis requires precise expression of various genes.This process involves a complex model of gene regulation,in which any deviation will lead to the occurrence of heart defects.Expression of Tbx2 in different species is ultimately confined to the atrioventricular canal in the non-ventricular myocardium,suggesting that the temporal and spatial expression of Tbx2 gene during cardiac development is highly consistent and evolutionarily conserved.As a member of the T-box transcription factor family,Tbx2 plays an important role in the differentiation of outflow tract and atrioventricular canal,leading to a series of changes in the regulatory pathway by regulating the transcription levels of the downstream target genes.At present,more and more studies have indicated that aberrant expressions or regulations of Tbx2 result in cardiac malformations in different model animals.In clinical studies,microdeletions/duplications in the fragments involving TBX2 and genetic variants in the non-coding region of this gene have also been reported in human congenital heart defects.Thus,this article is to review the advances in the effect and possible mechanisms for Tbx2 gene in cardiac development,and to discuss the relationship between this gene and congenital heart defects.

The progress of TBX20 gene mutation and all kinds of congenital heart diseases / 中华实用儿科临床杂志

TBX20 gene encodes a T - box transcription factor,which plays an important role in cardiac deve-lopment and in maintaining the maturation of cardiac function. TBX20 mutations are related to a variety of human con-genital heart diseases (CHD)that include atrial septal defect,ventricular septal defect,tetralogy of Fallot,double outlet right ventricle,dilated cardiomyopathy and other valvular diseases. This review focuses on the relationship between TBX20 gene and the development of heart,the TBX20 gene mutations newly found in patients with various CHD in re-cent years and their relationship,which will provide guide for further clinical research and possible intervention.

TBX2 gene mutation and the clinical significance of related proteins expression in ma-lignant peripheral nerve sheath tumor / 中国肿瘤临床

Objective:To detect genomic aberrations and investigate the expression and clinical significance of TBX2,CHK2, and p53 in malignant peripheral nerve sheath tumor (MPNST) tissues. Methods:We collected 63 cases of MPNST tissue samples, which were re-moved by resection and were confirmed by pathology, from January 1991 to December 2011 in Department of Bone and Sofer Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital. Twelve fresh tumor samples with qualified DNA quality were selected from the above 63 cases of tissue samples. Genome abnormalities of 12 MPNST tissues were detected by next-generation sequencing. The protein expression levels of TBX2, CHK2, and p53 in 63 MPNST tissue samples were assessed by immunohistochemistry staining. Results:One case of TBX2 gene mutation was observed out of the 12 MPNST tissue samples. In 63 MPNST tissue samples, the protein expression rates of TBX2, CHK2, and p53 were 60.3%(38/63), 47.6%(30/63), and 30.2%(19/63), respectively. TBX2 expression was sig-nificantly correlated with AJCC (American Joint Committee on Cancer, AJCC) stage, recurrence, and metastasis (P<0.05). TBX2 expres-sion was directly correlated with that of CHK2 (r=0.254, P=0.045), and CHK2 expression was directly correlated with that of p53 (r=0.343, P=0.006). In terms of the disease-free survival and overall survival time, patients with high expression levels of TBX2, CHK2, and p53 had significantly worse prognosis than patients with low expression levels of TBX2, CHK2, and p53(all P<0.05). TBX2, CHK2, and p53 were independent prognostic factors of MPNST. Conclusion:TBX2 and its associated proteins may play important roles in MPNST development and progression. Detecting TBX2 expression may provide the theoretical basis for estimating the prognosis of patients with MPNST.

Expression of TBX1 Gene in Kidney Tissues in Patients with Clear Cell Renal Cell Carcinoma and Its Clinical Significance / 中国医科大学学报

Objective To analyze the expression of TBX1 gene in kidney tissues in patients with clear cell renal cell carcinoma(ccRCC)and in?vestigate its molecular genetics mechanism during the tumor development. Methods Real?time quantitative polymerase chain reaction(qRT?PCR)was used to detect the expression of TBX1 mRNA in 12 cases of clear cell renal cell carcinoma tissues and the corresponding normal kidney tissues adjacent to carcinoma .The protein expression of TBX1 was assayed by Western blot in both groups. Results Both TBX1 mRNA level and the protein level were significantly up?regulated in ccRCC tissues compare to those in normal kidney tissues adjacent to carcinoma(all P<0.05). Conclusion Over?expression of TBX1 gene might be a potentially pathogenic mechanism of ccRCC.

PLCε regulates invasion and migration of human bladder cancer cells T 24 through PKCα/β/TBX3 pathway / 基础医学与临床

Objective To investigate the molecular mechanisms of PLCεin regulating the invasion and migration of human bladder cancer cells in vitro.Methods After cells treated with recombinant adenovirus , the migratory/in-vasive abilities of T24 cells were explored by wound healing and Transwell chamber cell migration and invasion as -say;RT-PCR was used to detect the mRNA levels of PLCε;The protein levels of PLCε,PKCα,PKCβ, TBX3 and E-cadherin were determined by Western blot;QRT-PCR was used to detect the mRNA levels of TBX3 and E-cad-herin.Results It was confirmed by digesting and sequencing that the recombinant adenovirus had been constructed successfully .The expression of PLCε mRNA and PLCε protein were both decreased after the infection of Ad-shPLCε.Wound healing and Transwell chamber cell migration/invasion assay showed that Ad-shPLCε treatment could inhibit the migratory and invasive activity of bladder cancer cells(P<0.05).The results of Western blot indicated that the expression of PKCα/βin membrane decreased ( P<0.05 ) , and phosphorylation level of PKCαand PKCβwas reduced .QRT-PCR and Western blot analysis demonstrated that the expression level of TBX 3 de-creased , but the expression level of E-cadherin increased .Conclusions PLCε shRNA can inhibit migratory and invasive ability of bladder cancer cells through PKCα/β/TBX3/E-cadherin pathway .

Mechanism of Tbx3 gene in tumor progression / 国际肿瘤学杂志

As a member of T-box family,Tbx3 (T-box3) is widely expressed in multiple organs and involves in the development of breast,limb,heart,eye,lung and pancreas during embryonic development stage.Moreover,Tbx3 plays an important role in maintaining the embryonic stem cells.Recent studies show that Tbx3 can work as a transcription factor to participate in the initiation and progression of tumor by epithelialmesenchymal transition,induction tumor stemness and methylation.A better understanding of Tbx3 will provide new insights into genetic diagnosis and targeted treatment of tumor.

miR-205 inhibits invasion of glioma cells via targeting TBX18 / 中国病理生理杂志

[ ABSTRACT] AIM:To explore the expression pattern of microRNA-205 ( miR-205) in glioma tissues and its role in the invasion of glioma cells.METHODS:The expression of miR-205 and TBX18 was detected by real-time PCR and immunohistochemical observation, respectively.Transwell assay was used to examine the invasion change of U251 glioma cells after miR-205 overexpression via miR-205 mimics or decrease in miR-205 expression by miR-205 inhibitor.The target of miR-205 was searched by bioinformatics analysis combined with experimental analysis.The protein level of TBX18 was determined by Western blotting after siRNA transfection and Transwell assay was conducted.RESULTS:miR-205 expres-sion was downregulated in 82.6%of detected glioma tissues and TBX18 was significantly overexpressed in glioma tissues compared with normal tissues.miR-205 overexpression remarkably inhibited the invasion potential of U251 glioma cells with a decrease in the invasive cells (P<0.01), while inhibition of miR-205 significantly enhanced the invasion ability of U251 cells.Mechanically, miR-205 directly targeted TBX18 and downregulation of TBX18 also significantly inhibited the invasion potential of U251 cells with a decrease in the invasive cells ( P<0.01 ) .CONCLUSION: miR-205 expression is de-creased in glioma, and miR-205 inhibits glioma cell invasion via targeting TBX18.Our research contributes to the mecha-nisms responsible for glioma invasion and provides theoretical base for developing new therapeutic strategy to treat glioma.

Association between Tbx20 gene polymorphism and congenital atrial septal defects / 中华内科杂志

Objective To investigate the association between single nucleotide polymorphisms (SPN) of Tbx20 gene and congenital atrial septal defects (ASD) in the Xinjiang Han population.Methods A total of 214 ASD patients and 382 controls were included in the present study.Two SNPs (rs17675131,rs4720169) in Tbx20 gene were genotyped by TaqMan SNP genotyping method.Results The distribution of the rs17675131 of Tbx20 were significantly different between normal controls and ASD patients (P =0.014),in which both the A/G allele distribution (P =0.004) and the dominant model (GG vs AG + AA) were significantly different between the 2 groups (P =0.007,OR =0.626).Same is true for the rs4720169 SNP.Its genotype showed significantly different distributions between the 2 groups (P =0.016) specifically for the A/G allele distribution frequencies (P =0.016) and the recessive model (AA vs AG + GG) (P =0.008,OR =1.96).The A-A haplotype was found to be associated with ASD.Conclusion Both rs17675131 and rs4720169 of Tbx20 gene are associated with congenital ASD in the Xinjiang Han population in China.

Progresses on relationship of conotruncal heart defects and retinoic acid signaling pathway / 国际儿科学杂志

Congenital conotruncal heart defects (CHD),including tetralogy of Fallot (TOF),double outlet of right ventricle(DORV),transposition of the great arteries(TGA),persistent truncus arteriosus (PTA),is a variety of common and serious congenital cardiovascular diseases which are threatenting to the health of neonates and infants.Previous studies have demostrated that TBX1 contricuted to some of the CHD.Recent studies have also confirmed that retinoic acid signaling pathway plays a curcial role of development of CHD.Further studies have also found that TGF-β2 differential expression is closely related with phenotypic polymorphism of conotruncal heart defects in retinoic acid receptor mutant mice,of which the mechanism is not yet clear.This paper provides an overview of the relationship between TBX1-RA signaling pathway and congenital conotruncal heart defects and TGF-β2-RA and CHD during the development of CHD.

Expressions and significances of TBX2 and MDM2 protein in urothelial carcinoma of bladder / 中国医师进修杂志

Objective To evaluate the expressions of TBX2 and MDM2 protein in urothelial carcinoma of bladder.Methods The expressions of TBX2 and MDM2 protein were examined by immunohistochemistry EnvisionTM Plus method in 90 cases of urothelial carcinoma of bladder and 20 cases of normal bladder mucosa tissue.Results The positive rate of TBX2 and MDM2 protein was 0 in normal bladder mucosa tissues.The positive rate of TBX2 in urothelial carcinoma of bladder was 65.6％ (59/90).With the increased of TBX2 expression degree,the carcinoma tissue was worse cell differentiation,later clinical stage,more prone to recurrence (P ＜ 0.01).The positive rate of MDM2 in urothelial carcinoma of bladder was 31.1％(28/90).With the decreased of carcinoma tissue differentiation degree,the positive rate of MDM2 was increased (P ＜ 0.01).The positive rate of MDM2 in recurrence patients was 57.5％ (23/40),in non-recurrence patients was 10.0％ (5/50),there was statistical difference (P ＜ 0.01).The positive rate of MDM2 in pTNM stage Ta-T1 was 0,in pTNM stage T2-T3 was 73.7％ (28/38),there was statistical difference (P ＜0.01).There was positive correlation between the expression of TBX2 and MDM2 in carcinoma tissue (r =0.487,P ＜ 0.05).Conclusions The over expression of TBX2 and MDM2 protein may closely associated with aggressive biological behavior and recurrence in urothelial carcinoma of bladder.Combined analysis of TBX2 and MDM2 may provide a theoretical basis for prognostic information and treatment of patients with urothelial carcinoma of bladder.

PROP1 overexpression in corticotrophinomas: evidence for the role of PROP1 in the maintenance of cells committed to corticotrophic differentiation

OBJECTIVE: The expression of transcription factors involved in early pituitary development, such as PROP1 and POU1F1, has been detected in pituitary adenoma tissues. In this study, we sought to characterize the transcriptional profiles of PROP1, POU1F1, and TBX19 in functioning and nonfunctioning pituitary adenomas in an attempt to identify their roles in tumorigenesis and hormone hypersecretion. METHODS: RT-qPCR analyses were performed to assess the transcriptional pattern of PROP1, POU1F1, TBX19, and hormone-producing genes in tissue samples of corticotrophinomas (n = 10), somatotrophinomas (n = 8), and nonfunctioning adenomas (n = 6). RESULTS: Compared with normal pituitary tissue, POU1F1 was overexpressed in somatotrophinomas by 3-fold. PROP1 expression was 18-fold higher in corticotrophinomas, 10-fold higher in somatotrophinomas, and 3-fold higher in nonfunctioning adenomas. TBX19 expression was 27-fold higher in corticotrophinomas. Additionally, the level of TBX19 mRNA positively correlated with that of pro-opiomelanocortin (r = 0.49, p = 0.014). CONCLUSIONS: Our data demonstrate that PROP1 is overexpressed in pituitary adenomas, mainly in corticotrophinomas. Together with previously published data showing that patients who harbor PROP1 loss-of-function mutations present a progressive decline in corticotrope function, our results support a role for PROP1 in pituitary tumor development and in the maintenance of cell lineages committed to corticotrophic differentiation. .

The Influence of CagA on the Differentiation of Helper T Lymphocytes in Chronic Gastritis / 天津医药

Objective To evaluate the influence of cytotoxin-associated gene A (CagA)to the differentiation of helper T lymphocytes in chronic gastritis. Methods Eighty patients with chronic gastritis were included in this study. The serum antibody against CagA was detected by the enzyme-linked immunosorbant assay (ELISA). Patients were divided into CagA-positive group and CagA-negative group according to the results of ELISA. Pathologic changes in gastric mucus were respectively analyzed. In addition, the expressions of nuclear transcription factors in gastric mucus including TBX 21, GATA-3, FoxP3 and Rorγt were detected by PCR and Western blot assay. Results There were 52 patients in CagA-positive group and 28 patients in CagA-negative group. The gastric inflammation was more serious in CagA-positive group than that in CagA-snegative group. There was no significant difference in Hp density between two groups. The expressions of GATA-3 and FoxP3 were much higher, while the transcription and protein expression levels of TBX21 and Rorγt were significantly lower in CagA-positive group than those in CagA-negative group. Conclusion Although the inflammation in gastric mucus was more serious in CagA-positive patients, Hp can not be effectively eliminated,which may relate to the differentiation of Th0 into Th2/Treg cells.