Loss of GLTSCR1 causes congenital heart defects by regulating NPPA transcription.

Precise and specific spatiotemporal domains of gene expression regulation are critical for embryonic development. Recent studies have identified GLTSCR1 as a gene transcriptional elongation regulator in cancer research. However, the function of GLTSCR1, especially in embryonic development, remains poorly understood. Here, we found that GLTSCR1 was essential for cardiac development because Gltscr1 knockout (Gltscr1-/-) led to embryonic lethality in mice with severe congenital heart defects (CHDs). Ventricular septal defect and double outflow right ventricular were also observed in neural crest cells with conditional deletion of Gltscr1, which were associated with neonatal lethality in mice. Mechanistically, GLTSCR1 deletion promoted NPPA expression by coordinating the CHD risk G allele of rs56153133 in the NPPA enhancer and releasing the transcription factor ZNF740-binding site on the NPPA promoter. These findings demonstrated that GLTSCR1 acts as a candidate CHD-related gene.

Retracted: The Clinical Effectiveness of Calcium Hydroxide in Root Canal Disinfection of Primary Teeth: A Meta-Analysis.

This publication has been retracted by the Editor due to non-original content and deficiencies in the conduct of the study. Reference: Liying Jia, Xiaolin Zhang, Hong Shi, Ting Li, Bingjian Lv, Meng Xie. The Clinical Effectiveness of Calcium Hydroxide in Root Canal Disinfection of Primary Teeth: A Meta-Analysis. Med Sci Monit, 2019; 25: 2908-216. DOI: 10.12659/MSM.913256.

The Clinical Effectiveness of Calcium Hydroxide in Root Canal Disinfection of Primary Teeth: A Meta-Analysis.

BACKGROUND The aim of this research was to systematically analyze the effectiveness of calcium hydroxide compared to formocresol (FC) and camphor phenol (CP) in root canal disinfection of primary teeth. MATERIAL AND METHODS The meta-analysis was based on the participants, interventions, control, outcome (PICO) study design principle and 16 randomized-controlled clinical trials published from January 2000 to August 2018. The data heterogeneity of each study was assessed by the Q-test. The odds ratio and 95% confidence interval (CI) were calculated based on the heterogeneity results by Revman software. RESULTS Sixteen randomized-controlled clinical trials of 3047 primary teeth were included in this meta-analysis. There were significant differences of clinical effectiveness between calcium hydroxide and FC in root canal disinfection of primary teeth (OR=3.37; 95% CI range: 2.54-4.48, P<0.01) and endodontic inter-appointment emergencies (EIAE) after disinfection for 7 days (OR=0.26; 95% CI range: 0.16-0.42, P<0.01). However, there was no statistical difference of EIAE, after disinfection of primary teeth for 48 hours, between calcium hydroxide and FC (OR=0.62; 95% CI range: 0.34-1.11, P=0.11). There were significant differences of clinical effectiveness between the calcium hydroxide and CP in root canal disinfection of primary teeth (OR=5.50; 95% CI range: 3.36-8.98, P<0.01). CONCLUSIONS This meta-analysis indicated that the effectiveness of calcium hydroxide as root canal disinfectant in primary teeth was more effective than that of FC and CP.

Er:YAG laser application in caries removal and cavity preparation in children: a meta-analysis.

The aim of this meta-analysis was to systematically evaluate the applications of Er:YAG lasers for the removal of caries and cavity preparation in children. The meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was conducted with data extracted from seven relevant randomized controlled trials (RCTs) published from 1997 to July 2017. The data heterogeneity of each study was assessed by a Q test. We used the heterogeneity results to calculate the standard mean difference (SMD) or relative risk (RR) and 95% confidence interval (95%CI) using STATA version 10.0. The publication bias was evaluated using Begger's test. There were seven randomized controlled trials included in this study. The analysis results indicate that compared to the conventional mechanical method, more time was needed for Er:YAG laser treatment (SMD 1.945, 95%CI 0.942 to 2.948). However, the pain reported by patients was reduced with Er:YAG laser treatment (SMD - 1.013, 95%CI - 1.892 to - 0.196). There were no significant differences between the groups in the complete retention rate (RR 1.021, 95%CI 0.963 to 1.114), the marginal discoloration (RR 1.638, 95% CI 0.240 to 11.986) and the marginal adaptation (RR 1.480, 95%CI 0.257 to 8.515). In conclusion, our data indicate that the time required for Er:YAG laser treatment was longer than that for the conventional mechanical method, but there was less pain associated with the Er:YAG laser treatment. There were no significant differences in the complete retention rate, marginal discoloration, and marginal adaptation between the two groups.

Large-sized pedunculated and polypoidal angiomyofibroblastoma of the vulva: A case report and literature review.

Angiomyofibroblastoma (AMF) represents a rare, benign mesenchymal tumor with a predilection for the vulvovaginal region, which may be misdiagnosed as aggressive angiomyxoma (AAM). Herein, we report a case of a 20-year-old nulliparous Chinese woman with a unique pedunculated and polypoidal mass, which had been developing within the previous 6 months in the left labium majus, exhibiting the AAM clinical impression but diagnosed as AMF. The mass measured 18 × 10 × 6 cm, and contained diffuse ulcerated areas and purulent discharge. A complete excision of the mass was performed. There was no subsequent evidence of recurrence, according to a 13-month follow-up. As a rare benign vulvovaginal tumor, AMF can present on patients of an early reproductive age with rapidly growing, polypoidal pattern. The whole exon sequencing analysis revealed the genomic alterations, which may contribute to the occurrence of AMF.

[Exploration of carcinogenesis based on tree models using CGH data].

Comparative genomic hybridization (CGH) can detect chromosomal deletions and amplifications of tumors, and various laboratories and public databases have accumulated a large number of CGH data, providing the opportunity to analyze the molecular mechanism of tumorigenesis in the whole genome. Tree models are generally used to study the history of biological formation and evolution in the field of bioinformatics, and evolutionary relationships between species are usually represented using phylogenetic tree. Tree models are also powerful bioinformatics tools to analyze CGH data and explore carcinogenesis. Two common tree models, the branching tree and the distanced-based tree, as well as their basic principles, methods are introduced detailedly, several technical problems in construction of tree models are discussed, and their applications in cancer research are reviewed systematically in this paper. As a generalization of single path linear model, tree models can more accurately conclude multigene, multistep, multipathway process of tumorigenesis, exploring the molecular mechanism of tumorigenesis from different angels. Apart from CGH data, tree models can be used to analyze various types of data, including high-resolution data (e.g., array-CGH data).

IGFBP7 plays a potential tumor suppressor role in colorectal carcinogenesis.

Insulin-like growth factor binding protein-7 (IGFBP7) is a gene identified as being low expressed in colorectal adenocarcinoma (CRC) cell lines. In the current study, we investigated the function of IGFBP7 in CRC by transfection studies. We found that IGFBP7 could inhibit cell growth, decrease soft agar colony formation activity and induce apoptosis in RKO and SW620 cells. Correlation analysis between the expression of IGFBP7 in CRC tissue and the prognosis in 218 patients showed that high expression of IGFBP7 was associated with favorable prognosis. Based on above results, we conclude that IGFBP7 plays a potential tumor suppressor role in colorectal carcinogenesis.

Identification of a novel VNTR polymorphism in C6orf37 and its association with colorectal cancer risk in Chinese population.

BACKGROUND: C6orf37 was a gene up-regulated in colorectal adenoma in our previous study. A variable region of C6orf37 sequence was found when we blasted its full sequence with NCBI nucleotide database. METHODS: RT-PCR and sequencing were conducted to identify the variable region of C6orf37 as VNTR. DHPLC was applied to detect the VNTR genotypes in 122 colorectal carcinoma patients and 166 healthy controls. RESULTS: A novel VNTR sequence found in C6orf37 second exon was composed of 15 base pair consensus sequence encoding 5-amino-acid (G-G-D-F-G). The repeat timePOST alleles contain three repeats (a), 4 repeats (b) and 5 repeats (c), respectively, which produced 3 homozygotes (a/a, b/b and c/c) and 3 heterozygotes (a/b, a/c and b/c). a, b, c allele frequencies were 0.145, 0.304, 0.551, respectively in Chinese population. Heterozygosity (H) was 0.583. Polymorphism information content (PIC) was 0.510. The distribution of genotypes and allele frequencies of the VNTR reached no significant difference between patients and healthy controls and there was no correlation between VNTR polymorphism and colorectal cancer clincopathological features. CONCLUSION: A novel VNTR polymorphism in C6orf37 exists in Chinese population and is not associated with colorectal cancer risk.

IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis with its expression associated with DNA hypomethylation of exon 1.

Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR (MSP) and bisulfite sodium PCR (BSP), we found that its expression was associated with DNA hypomethylation of exon1. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2'-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the functional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony formation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.

DHPLC analysis of the matrix metalloproteinase-1 promoter 1G/2G polymorphism that can be easily used to screen large population.

Matrix metalloproteinase-1 has been shown to play an important role in all stages of cancer initiation, invasion, and metastasis. The 1G/2G single nucleotide polymorphism (SNP) at -1607 to -1608 creates an Ets binding site and elevates the rate of transcription. Moreover, the presence of the 2G allele in the MMP-1 promoter has been reported to be associated with the development and/or progression of carcinomas of the ovary, endometrium, lung, and colorectum. However, further studies on a wide variety of cancers in various sufficiently large populations will be required to verify that 2G is risk factor for cancers. A major challenge confronting such studies is the need to develop accurate, fast and inexpensive high-throughput genotyping techniques. To set up a fast and sensitive test for MMP-1 1G/2G genotyping, we analyzed 126 healthy persons by denaturing high performance liquid chromatography (DHPLC). The genotypes of MMP-1 1G/2G revealed by DHPLC analysis were further confirmed by DNA sequencing. In conclusion, DHPLC is a cost-effective, rapid, sensitive, and high-throughput technique for MMP-1 1G/2G genotyping.

Concurrent tamoxifen-related Müllerian adenofibromas in uterus and ovary.

Tamoxifen is a widely used in anti-oestrogen treatment of breast cancer. Previous reports showed that tamoxifen is associated with proliferative endometrial lesions. We herein reported an unusual case of concurrent hyperplastic lesions in the uterine cavity and right ovary in a 45-year-old woman with tamoxifen therapy. Regular vaginal ultrasonography showed the progressive endometrial thickening and right ovary enlargement during the period of drug use. Both lesions in the uterine cavity and right ovary showed characteristics resembling that of Müllerian adenofibroma. There were also foci of endometriosis in her bilateral ovarian surfaces. We suggest that women taking tamoxifen with a known history of endometriosis should be followed with transvaginal ultrasonography periodically.

Overexpression of Reg IV in colorectal adenoma.

Identification of molecular markers associated with colorectal adenoma may uncover critical events involved in the initiation and progression of colorectal cancer. Our previous studies, mainly based on suppression subtractive hybridization, have identified Reg IV as a strong candidate for a gene that is highly expressed in colorectal adenoma when compared to normal mucosa. In this study, we sought to determine the mRNA expression of Reg IV in colorectal adenoma, in comparison with normal colorectal mucosa and carcinoma in multiple samples. Semi-quantitative RT-PCR was performed in 12 colorectal adenomas and 10 concurrent carcinomas. Reg IV mRNA level was higher in all adenomas (12/12) (p=0.001) and in 9/10 concurrent colorectal carcinoma (p=0.021) when compared to paired normal colorectal mucosa. Northern blot analysis further confirmed these results. In situ hybridization with digoxigenin (DIG)-labeled cRNA was performed in 32 colorectal adenomas with varying degree of dysplasia. Compared with paired normal tissues, Reg IV was overexpressed in 74% (14/19) adenomas with mild or moderate dysplasia and 100% (13/13) cases of adenoma with severe dysplasia. In addition, higher levels of Reg IV mRNA was consistently scored in regions with more severe dysplasia within the same adenoma sample displaying varying degree of dysplasia. The strongest staining was seen within carcinomoutous areas of the 12 adenoma cases (p=0.002). Our results support that overexpression of Reg IV may be an early event in colorectal carcinogenesis. Detection of Reg IV overexpression may be useful in the early diagnosis of carcinomatous transformation of adenoma.

A novel mouse model for colitis-associated colon carcinogenesis induced by 1,2-dimethylhydrazine and dextran sulfate sodium.

AIM: To develop an efficient animal colitis-associated carcinogenesis model and to detect the expression of beta-catenin and p53 in this new model. METHODS: Dysplasia and cancer were investigated in mice pretreated with a single intraperitoneal injection of 20 mg/kg body mass of 1,2-dimethylhydrazine prior to three repetitive oral administrations of 30 g/L dextran sulfate sodium to give conditions similar to the clinically observed active and remission phases. Immunohistochemical staining of beta-catenin and p53 was performed on paraffin-imbedded specimens of animals with cancer and/or dysplasia, those without dysplasia and the normal control animals. RESULTS: At wk 11, four early-invasive adenocarcinomas and 36 dysplasia were found in 10 (90.9%) of the 11 mice that underwent 1,2-dimethylhydrazine-pretreatment with 3 cycles of 30 g/L dextran sulfate sodium-exposure. Dysplasia and/or cancer occurred as flat lesions or as dysplasia-associated lesion or mass (DALM) as observed in humans. Colorectal carcinogenesis occurred primarily on the distal portion of the large intestine. No dysplasia and/or cancer lesion was observed in the control groups with 1,2-dimethylhydrazine pretreatment or 3 cycles of 30 g/L dextran sulfate sodium exposure alone. Immunohistochemical investigation revealed that beta-catenin was translocated from cell membrane to cytoplasm and/or nucleus in 100% of cases with dysplasia and neoplasm, while normal membrane staining was observed in cases without dysplasia and the normal control animals. Nuclear expression of p53 was not detected in specimens. CONCLUSION: A single dose of procarcinogen followed by induction of chronic ulcerative colitis results in a high incidence of colorectal dysplasia and cancer. Abnormal expression of beta-catenin occurs frequently in dysplasia and cancer. This novel mouse model may provide an excellent vehicle for studying colitis-related colon carcinogenesis.

Effect of vascular endothelial growth factor on retinal ganglion cells of rats with chronic intraocular hypertension.

AIM: To investigate the effect of vascular endothelial growth factor (VEGF) on the expression of pigment epithelium-derived factor (PEDF) in retina and the protective effect of VEGF on retinal ganglion cells (RGCs) of rats with chronic elevated intraocular pressure (EIOP) and it's potential mechanism. METHODS: 30 females Sprague-Dawley rats were randomly divided into three groups: EIOP + VEGF group (A), EIOP + vehicle group (B) and sham operated + VEGF group (C). The EIOP was introduced by obstructing episcleral veins in Group A and Group B. In the Group C, only the bulber conjunctiva was opened without obstructing episcleral veins. Immediately after surgery, rats in the Group A and Group C were intravitreously injected with 2 µL of VEGF. In the Group B, rats were intravitreously treated with 2 µL of normal saline. At 3 and 14 days after injection, animals were sacrificed and the eyes were collected for preparation of frozen sections. RESULTS: After surgery, the IOP increased significantly in the Group A and Group B. There was no significant difference in the IOP at day 3 and day 14 after operation. The PEDF expression in the Group A and Group B was higher than that in the Group C. TUNEL staining showed the apoptotic RGCs markedly reduced after VEGF treatment when compared with rats without treatment. CONCLUSION: Intravitreal treatment with VEGF may reduce the apoptosis of RGCs in rats with chronic intraocular hypertension.

Multiple genital tract tumors and mucinous adenocarcinoma of colon in a woman with Peutz-Jeghers syndrome: a case report and review of literatures.

We report a very rare case of Peutz-Jeghers syndrome (PJS) composed of multiple genital tract tumors and mucinous adenocarcinoma. A 46-year-old woman presented to our hospital with lower abdominal pain resulting from PJS involves sex cord tumor with annular tubules (SCTAT), ovarian mucinous tumor, ovarian serous tumor, mucinous adenocarcinoma of colon. The CEA concentration is high before surgery, and decreases after the surgery and subsequent chemoradiotherapy. This case demonstrates a classic clinical presentation of a patient with PJS. PJS patients have increased risk of malignancy and early detection and regular surveillance of the high-risk patients with PJS is crucial. Surgery may be required for obstructive gastrointestinal lesions as well as those exhibiting malignant degeneration.

Low-dose mifepristone increases uterine expression of aquaporin 1/aquaporin 2 at the time of implantation.

BACKGROUND: The aim of this study was to investigate the mechanism by which low-dose mifepristone serves as an antiimplantation contraceptive drug. A human endometrial explant system was used to study the effects of low-dose mifepristone (65 nmol/L and 200 nmol/L) on expression of the water channel family aquaporins, aquaporin-1 and aquaporin-2 (AQP1/AQP2), at the time of implantation. STUDY DESIGN: Endometrial samples from 17 normally cycling patients at the "window of implantation" were treated with different concentrations of mifepristone. The protein and mRNA expression of AQP1/AQP2 in the endometrium was examined using immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. RESULTS: The IHC and RT-PCR analyses demonstrated that expression of AQP1/AQP2 was increased by mifepristone in a dose-dependent manner, with the highest AQP1/AQP2 expression levels detected in subjects treated with 200-nmol/L mifepristone. CONCLUSION: Low-dose mifepristone may negatively regulate implantation by increasing AQP1/AQP2 protein and mRNA expression. The findings from this study provide further evidence to support the potential contraceptive activity of low-dose mifepristone.

RegIV expression showing specificity to gastrointestinal tract and its potential role in diagnosing digestive tract neuroendocrine tumor.

Regenerating gene IV (RegIV), a member of the regenerating gene family discovered in 2001, has been found to be involved in malignancy in several different organs including the stomach, colorectum, pancreas and prostate, but the overall expression profile of RegIV has not been reported. To learn more about RegIV, we evaluated its distribution by immunohistochemistry (IHC) in a total of 360 samples including 24 types of normal tissue, 40 benign and malignant lesions, and 18 neuroendocrine tumors. We found that in normal tissues, in addition to its relative specificity for the gastrointestinal tract, RegIV was detected in the adrenal gland and mammary gland. Among all the malignancies of various histological types under evaluation, RegIV was found mostly in adenocarcinomas. Studies on additional sets of colorectal tumor samples showed that RegIV expression was predominant in colorectal adenoma (87.5%) and peritumoral tissue (100%) but not in cancer tissue (30.8%). Among neuroendocrine tumors, RegIV had a relatively restricted expression to those of digestive system.

A single nucleotide polymorphism in the matrix metalloproteinase-2 promoter is associated with colorectal cancer.

Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against matrix proteins, particularly basement membrane constituents. A single nucleotide polymorphism C-->T transition at -1306, which disrupts an Sp1-type promoter site (CCACC box), displayed a strikingly lower promoter activity with T allele. Our study investigated whether the MMP-2 -1306 C-->T polymorphism contributed to the development and progression of colorectal cancer in the Chinese population. One hundred twenty-six colorectal cancer patients and 126 age- and sex-matched controls were included in this study. PCR-based denaturing high performance liquid chromatography analysis and sequencing were used to determine the MMP-2 genotypes. MMP-2 expression of each genotype was analyzed in four colorectal cancer cell lines by semi-quantitative RT-PCR. The correlation between the genotypes and clinicopathological parameters among colorectal cancer cases was investigated. The results showed that the levels of MMP-2 mRNA expression in cell lines containing CC genotype were much higher compared with cell with CT genotype. The frequency of MMP-2 CC genotype was significantly higher in colorectal cancer patients when compared with controls (OR, 1.959; 95% CI, 1.055-3.637). Colorectal cancers with CC genotype were more common with serosa/adventitia layer involvement compared with CT+TT genotypes. Our data suggest that MMP-2 -1306 C-->T polymorphism may be associated with colorectal cancer development and invasion in the Chinese population.