GSK3B inhibition reduced cervical cancer cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition.

Previous studies show that glycogen synthase kinase 3ß (GSK3B) plays an important role in tumorigenesis. However, its role in cervical cancer is unclear. The present study silenced GSK3B with siRNAs and/or chemical inhibitors to determine its role in HeLa cervical cancer cell proliferation and migration as well as in xenograft tumor growth. Cell Counting Kit (CCK)-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to determine cell survival and proliferation. Scratch and Transwell® assays were used to evaluate cell migration. Xenograft tumors were used to evaluate the effect of GSK3B on tumor growth. Transcriptomic sequencing was used to clarify the mechanisms underlying the foregoing processes. Public databases and clinical specimens showed that GSK3B was upregulated in cervical cancer tissues and correlated with poor prognosis. In vitro experiments indicated that GSK3B inhibition reduced cell viability, proliferation, and migration. In vivo experiments demonstrated that GSK3B inhibition slowed xenograft tumor growth. Transcriptomic sequencing revealed that GSK3B inhibition modulated the phosphatidylinositol 3-carboxykinase (PI3K)/protein kinase B (Akt) and extracellular matrix (ECM)-receptor interaction signaling pathways. GSK3B inhibition decreased the protein levels of phosphorylated PI3K and Akt and the levels of mesenchymal markers but increased those of epithelial markers. An activator of the PI3K/Akt signaling pathway counteracted the suppressive effects of GSK3B inhibition on HeLa cell viability and proliferation and on PI3K/Akt signaling. Our data suggested that GSK3B regulated cervical cancer cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition (EMT).

Evaluation of thickness of individual macular retinal layers in diabetic eyes from optical coherence tomography.

The effect of diabetes mellitus (DM) on individual retinal layers remains incompletely understood. We evaluated the intra-retinal layer thickness alterations in 71 DM eyes with no diabetic retinopathy (DR), 90 with mild DR, and 63 with moderate DR without macular edema, using spectral-domain optical coherence tomography (SD-OCT) and the Iowa Reference Algorithm for automated retinal layer segmentation. The average thickness of 10 intra-retinal layers was then corrected for ocular magnification using axial length measurements, and pairwise comparisons were made using multivariable linear regression models adjusted for gender and race. In DM no DR eyes, significant thinning was evident in the ganglion cell layer (GCL; p < 0.001), inner nuclear layer (INL; p = 0.001), and retinal pigment epithelium (RPE; p = 0.014) compared to normal eyes. Additionally, mild DR eyes exhibited a thinner inner plexiform layer (IPL; p = 0.008) than DM no DR eyes. Conversely, moderate DR eyes displayed thickening in the INL, outer nuclear layer, IPL, and retinal nerve fiber layer (all p ≤ 0.002), with notably worse vision. These findings highlight distinctive patterns: early diabetic eyes experience thinning in specific retinal layers, while moderate DR eyes exhibit thickening of certain layers and slightly compromised visual acuity, despite the absence of macular edema. Understanding these structural changes is crucial for comprehending diabetic eye complications.

Metastasis of ovarian dysgerminoma in a postmenopausal patient: a rare case report.

Ovary dysgerminoma is one of the most good prognosis malignant tumor, which has a 5-year overall survival rate exceeding to 90%. Generally, the incidence of ovarian dysgerminoma (OD) is relatively low, accounting for ~0.6% of all ovarian tumors. Usually, it mainly occurs in very young women, about 85% of patients under 30 years old and is rare in middle-aged especially in elderly ones. This ovary dysgerminoma case report presents a 58-year-old menopausal postmenopausal woman which has a poor prognosis. Therefore, there may be differences between the elderly and young women in clinical characteristic that require separate management. This case reports a postmenopausal woman who was diagnosed with ovary dysgerminoma. After surgery, the patient was treated chemotherapy with bleomycin, etoposide, and cisplatin (BEP) according to the treatment guidelines. Unusually, the patient developed bone marrow suppression and lymph node metastasis in final. This report explored the clinical characteristic in postmenopausal woman dysgerminoma. Changes in lactate dehydrogenase (LDH) throughout the course of the disease are closely related to the progression. The patient had a disease progression when treated with the conventional treatment (BEP). The applicability of this treatment protocol to postmenopausal patients requires further research. Postmenopausal woman dysgerminoma is rare but rapid progress. Whether BEP is suitable for OD in middle-aged and elderly people remains to be further validated in the future. LDH may be a potential biomarker for monitoring the progression of OD in the elderly.

Discovery of novel itaconimide-based derivatives as potent HDAC inhibitors for the efficient treatment of prostate cancer.

Histone deacetylases (HDACs) are a family of enzymes that play important roles in the development and progression of cancers. Inhibition of HDACs has been widely studied as a therapeutic strategy in the development of anticancer drugs. However, developing HDAC inhibitors that are effective for solid tumors remains a great challenge. In this work, we designed and synthesized a series of itaconimide-based derivatives as potent HDAC inhibitors. Among them, compound 17q exhibited potent inhibition of HDAC1/2/3/6, with good antiproliferative activity in vitro and an excellent pharmacokinetic profile. Compound 17q significantly inhibited tumor growth in a DU145 xenograft tumor model and showed no obvious toxicity. Moreover, when 17q was combined with other prostate cancer therapeutics, outstanding synergistic effects were observed and the toxic side effects of DTX were reduced. Overall, based on the data, these inhibitors may offer promising new targeted therapies for prostate cancer.

GSK3B inhibition reduced cervical cancer cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition

Previous studies show that glycogen synthase kinase 3β (GSK3B) plays an important role in tumorigenesis. However, its role in cervical cancer is unclear. The present study silenced GSK3B with siRNAs and/or chemical inhibitors to determine its role in HeLa cervical cancer cell proliferation and migration as well as in xenograft tumor growth. Cell Counting Kit (CCK)-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to determine cell survival and proliferation. Scratch and Transwell® assays were used to evaluate cell migration. Xenograft tumors were used to evaluate the effect of GSK3B on tumor growth. Transcriptomic sequencing was used to clarify the mechanisms underlying the foregoing processes. Public databases and clinical specimens showed that GSK3B was upregulated in cervical cancer tissues and correlated with poor prognosis. In vitro experiments indicated that GSK3B inhibition reduced cell viability, proliferation, and migration. In vivo experiments demonstrated that GSK3B inhibition slowed xenograft tumor growth. Transcriptomic sequencing revealed that GSK3B inhibition modulated the phosphatidylinositol 3-carboxykinase (PI3K)/protein kinase B (Akt) and extracellular matrix (ECM)-receptor interaction signaling pathways. GSK3B inhibition decreased the protein levels of phosphorylated PI3K and Akt and the levels of mesenchymal markers but increased those of epithelial markers. An activator of the PI3K/Akt signaling pathway counteracted the suppressive effects of GSK3B inhibition on HeLa cell viability and proliferation and on PI3K/Akt signaling. Our data suggested that GSK3B regulated cervical cancer cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition (EMT).

miR-636 represses cell survival by targeting CDK6/Bcl-2 in cervical cancer.

Cervical cancer is widely known as one of the most common types of cancer diagnosed in women, and microRNAs (miRNAs) has been characterized as an important regulator in tumor progression, such as cervical cancer. MiR-636 was found to play a tumor suppressor role in hepatocellular carcinoma tumorigenesis. However, the tumorigenic mechanism of miR-636 on cervical cancer has not yet been found. In the present study, we first found that miR-636 was significantly downregulated in cervical cancer tissues and cell lines. in vitro gain- and loss-of-function assays revealed that overexpression of miR-636 inhibited cell proliferation and induced cell apoptosis, while knockdown of miR-636 reversed the effect on cervical tumorigenesis. Furthermore, cyclin-dependent kinase 6 (CDK6) and B-cell lymphoma 2 (Bcl-2) were characterized as targets of miR-636. Notably, overexpression of CDK6 or Bcl-2 could reverse the inhibitory effect of miR-636 on cervical cancer progression. Mechanistically, miR-636 repressed cell survival by targeting CDK6/Bcl-2 in cervical cancer, which may be the underlying mechanism of miR-636-inhibited cervical progression. In conclusion, our findings clarified the biologic significance of miR-636/CDK6/Bcl-2 axis in cervical cancer progression and suggested the potential therapeutic target ability of miR-636 in treatment of cervical cancer.

[Analysis of human papilloma virus infection of women in early pregnancy and postpartum].

OBJECTIVE: To explore the clinical value of examination of cervical HPV infection in women in early pregnancy and postpartum. METHODS: Using flow-through hybridization and gene chip techniques, we examined 3 806 cervical specimens of pregnant and postpartum women of different ages with different cervical diseases. The women were grouped into different age groups by every 5 years for HPV DNA genotyping of the specimens, with another 4080 women without pregnancy serving as the control. RESULTS: Of the total of 7886 specimens, high-risk HPV infection was detected a the rate of 12.5%. In pregnancy, postpartum and nonpregnancy, the infection rate was 14.3%,, 10.5%, and 11.7%, respectively. In the 4 age groups, the infection rate was 16.9%, 12.1%, 13.8%, and 22.1%, respectively. CONCLUSION: The high-risk HPV infection rate in pregnancy differs significantly from that in nonpregnancy and postpartum. The infection rate also differs with age during pregnancy and postpartum. Examination of HPV infection during pregnancy is safe and feasible.