The endometrial cancer detection using non-invasive hypermethylation of CDO1 and CELF4 genes in women with postmenopausal bleeding in Northwest China.

Objective: The objective of this study was to verify the clinical predictive performance of methylated cysteine dioxygenase type 1 (CDO1m) and CUGBP Elav-like family member 4 (CELF4m) in endometrial cancer (EC) women with postmenopausal bleeding (PMB). Material and Methods: A single-center, prospective, and case-control study was conducted in the Gansu Provincial Maternity and Child-care Hospital with 138 female postmenopausal patients enrolled in 2022. All patients underwent body mass index (BMI) detection, transvaginal ultrasonography (TVUS) detection, carbohydrate antigen 125 detection, and the cervical exfoliated cell CDO1/CELF4 gene methylation detection to analyze the sensitivity, specificity, and accuracy of different screening tests statistically with the biopsy and/or dilation and curettage (D&C) pathological diagnosis under hysteroscopy as the gold standard. Results: There was no significant difference in age between the EC group and the non-EC group, P = 0.492. Using quantitative polymerase chain reaction (qPCR) technology, we validated the CDO1 and CELF4 methylation detection with 87.5% sensitivity and 95.9% specificity as a useful strategy for the triage of women with PMB for the detection of EC. In addition, 100% of type II EC (n = 6) were positively detected by the CDO1 or CELF4 methylation test. Conclusion: The CDO1 and CELF4 methylation test with high specificity as an auxiliary diagnostic tool or alternative method provides physicians with a reference to distinguish between benign and malignant tumors in women with postmenopausal bleeding, to justify the necessity of using invasive methods to confirm diagnosis.

Clinicopathological features, therapeutic options, and significance of CD103 expression in 15 patients with follicular mucinosis.

Background: Follicular mucinosis (FM) is generally divided into a primary benign idiopathic form and a secondary form associated with mycosis fungoides. Objective: To analyze the clinical and pathological features of FM and explore the pathological significance of CD103 expression. Methods: In this case series, we retrospective analysis the clinical, pathological, treatment and follow-up treatment of 15 cases of FM. The expression of CD103 in all cases was detected by immunohistochemistry. Result: A total of 15 patients were enrolled, 7 were primary follicular mucinosis (P-FM) and 8 were mycosis fungoides-associated follicular mucinosis (MF-FM). Lesions of both P-FM and MF-FM are difficult to distinguish, present with red or dark red plaques and follicular papules. Pathologically, MF-FM showed more significant infiltrates of folliculotropic lymphoid cells, and the amount and proportion of CD103+ cells were significantly higher than that in P-FM. Follow-up data were available for 13 patients. Three cases were resolved after surgical resection, two patients were marked improved after oral administration of hydroxychloroquine and three times ALA photodynamic therapy respectively. The rest patients showed only modest efficacy. Conclusion: FM should be differentiated based on pathological characteristics and treatment response, CD103 is helpful in differential diagnosis of FM.

Florigen repression complexes involving rice CENTRORADIALIS2 regulate grain size.

Grain size is one of the crucial factors determining grain yield. However, the genetic and molecular mechanisms of florigen repression complexes (FRCs) underlying grain size in rice (Oryza sativa L.) have not been reported. Here, we report that the rice CENTRORADIALIS (CEN) family member OsCEN2 (also known as Rice TFL1/CEN homolog, RCN1), a phosphatidylethanolamine-binding protein (PEBP) family protein, negatively controls grain size in rice. Overexpression of OsCEN2 led to small grains, and knockout of OsCEN2 resulted in large, heavy grains. OsCEN2 influenced grain size by restricting cell expansion in the spikelet hull and seed filling. In in vivo and in vitro experiments, OsCEN2 physically interacted with a G-box factor 14-3-3 homolog, GF14f, which negatively regulates grain size. Bimolecular fluorescence complementation and yeast two-hybrid assays revealed that GF14f directly interacts with the basic leucine zipper (bZIP) transcription factor, OsFD2. Plants overexpressing OsFD2 produced smaller and lighter grains than wild-type plants. We found that OsFD2 also influences grain size by controlling cell expansion and division in the spikelet hull. Our results reveal the molecular mechanisms of the OsCEN2-GF14f-OsFD2 regulatory module in controlling grain size. Additionally, our study provides insight into the functions of the FRC in rice and suggests a strategy for improving seed size and weight.

Characterization of E-cadherin expression in normal mucosa, dysplasia and adenocarcinoma of gastric cardia and its influence on prognosis.

BACKGROUND: Gastric cardia adenocarcinoma (GCA), which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries, is of similar geographic distribution with esophageal squamous cell carcinoma in China, and even referred as "sister cancer" by Chinese oncologists. The molecular mechanism for GCA is largely unknown. Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers. However, the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis. AIM: To characterize E-cadherin expression in normal gastric cardia mucosa, dysplasia and GCA tissues, and its influence on prognosis for GCA. METHODS: A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases. The enrollment criteria included radical surgery for GCA, but without any radio- or chemo-therapy before operation. The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue (n = 208) and dysplasia lesions (n = 156) were collected, and processed as tissue microarray for immunohistochemistry. The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter, telephone or home interview. E-cadherin protein expression was determined by two step immunohistochemistry. Kaplan-Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients. RESULTS: Of the 4561 GCA patients, there were 3607 males with a mean age of 61.6 ± 8.8 and 954 females with a mean age of 61.9 ± 8.6 years, respectively. With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA, the positive immunostaining rates for E-cadherin decreased significantly from 100% to 93.0% and 84.1%, respectively (R2 = 0.9948). Furthermore, E-cadherin positive immunostaining rate was significantly higher in patients at early stage (0 and I) than in those at late stage (II and III) (92.7% vs 83.7%, P = 0.001). E-cadherin positive expression rate was significantly associated with degree of differentiation (P = 0.001) and invasion depth (P < 0.001). Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative (P = 0.026). It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis. However, in patients with negative lymph node metastasis, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.036). Similarly, in patients with late stage GCA, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.011). CONCLUSION: E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.

Corrigendum to "Antroquinonol Exerts Immunosuppressive Effect on CD8+ T Cell Proliferation and Activation to Resist Depigmentation Induced by H2O2".

[This corrects the article DOI: 10.1155/2017/9303054.].

IGF-1 resist oxidative damage to HaCaT and depigmentation in mice treated with H2O2.

Vitiligo, an acquired pigmentary disorder of the skin, is characterized by a chronic and progressive loss of melanocyte from the epidermis and follicular reservoir. Growth factor of surrounding cells impacted on melanocytes survival. In this study, lower level of IGF-1 in the lesion was found than that in the donor area of vitiligo patients. IGF-1 improved activation of Nrf2, and inhibited ROS generation and endoplasmic reticulum dilation in HaCaT. C57BL/6 mice were treated with 5% H2O2, and combined with 50 µg/kg of IGF-1 pre-treatment or not once every day for 50 consecutive days. After 50 days, IGF-1 obviously ameliorated depigmentation of mice skin and reduced hair follicle length, skin thickness and Tyrosinase induced by H2O2. Moreover, IGF-1 significantly suppressed CD8+ T cells infiltration in mice skin, inhibited the production of IL-2 and IFN-γ, and decreased the expression of CXCL10 and CXCR3. Thus, the results indicated that IGF-1 could resist oxidative damage to HaCaT, suppress CD8+ T cells infiltration and pro-inflammatory cytokines secretion, and suppresses the thinning of epidermal layer in vivo. It suggests that IGF-1 inhibits oxidative damage to HaCaT and immunosuppressive effects on CD8+ T cells proliferation and activation to resist depigmentation induced by H2O2. This disclosed its multiple roles in the vitiligo, and shed a light on developing the application potential for IGF-1 in vitiligo.

Antroquinonol Exerts Immunosuppressive Effect on CD8+ T Cell Proliferation and Activation to Resist Depigmentation Induced by H2O2.

Antroquinonol was investigated as antioxidant and inhibition of inflammatory responses. Our study was to evaluate its immunosuppressive effect on CD8+ T cells and protective effect on depigmentation. CD8+ T cells were treated with antroquinonol in vitro, and C57BL/6 mice were treated with antroquinonol with or without H2O2in vivo for 50 consecutive days. We found antroquinonol could inhibit proliferation of CD8+ T cells and suppress the production of cytokines IL-2 and IFN-γ and T cell activation markers CD69 and CD137 in vitro. H2O2 treatment induced depigmentation and reduced hair follicle length, skin thickness, and tyrosinase expression in vivo. Whereas, antroquinonol obviously ameliorated depigmentation of mice skin and resisted the reduction of hair follicle length, skin thickness, and tyrosinase expression induced by H2O2. Antroquinonol decreased CD8+ T cell infiltration in mice skin, inhibited the production of IL-2 and IFN-γ, and decreased the expression of CXCL10 and CXCR3. Summarily, our data shows antroquinonol inhibits CD8+ T cell proliferation in vitro. It also reduces CD8+ T cell infiltration and proinflammatory cytokine secretion and suppresses the thinning of epidermal layer in vivo. Our findings suggest that antroquinonol exerts immunosuppressive effects on CD8+ T cell proliferation and activation to resist depigmentation induced by H2O2.

Effect of a chemical inhibitor of human phosphatidylethanolamine-binding protein 4 on radiosensitivity of rectal cancer cells.

BACKGROUND: Human phosphatidylethanolamine-binding protein 4 (hPEBP4) is a well-established antiapoptosis molecule in recent years. It has also been demonstrated to be involved in the radioresistance of rectal cancer. The objective of this study was to determine whether IOI-42, a chemical inhibitor of hPEBP4, could sensitize rectal cancer cells. METHODS: Rectal cancer cells were treated with IOI-42 alone or in combination with irradiation. Clonogenic survival assays and tumor volume growth analysis were used, respectively, to study the effect of IOI-42 in vitro and in vivo. Western blot was adopted to measure the activation of signal pathway. RESULTS: Clonogenic survival assays showed that IOI-42, combined with irradiation, caused a significant decrease in colony formation compared with radiation alone, which was associated with the downregulation of Akt activation. And we also confirmed the effect of IOI-42 in nude mice transplanted with human rectal cancer subcutaneously. CONCLUSIONS: These data suggest that IOI-42 has a potential to enhance the radiosensitivity of rectal cancer cells, providing a rationale to further investigate the feasibility of combining of IOI-42 with radiation, keeping in mind that this may result in unexpected toxicities.