High expression levels of centromere protein O participates in cell proliferation of human ovarian cancer.

Ovarian cancer is a common malignant tumor in women, with a high mortality rate ranking first among gynecological tumors. Currently, there is insufficient understanding of the causes, pathogenesis, recurrence and metastasis of ovarian cancer, and early diagnosis and treatment still face great challenges. The sensitivity and specificity of existing ovarian cancer screening methods are still unsatisfactory. Centromere protein O (CENP-O) is a recently discovered structural centromere protein that is involved in cell death and is essential for spindle assembly, chromosome separation, and checkpoint signaling during mitosis. The abnormal high expression of CENP-O was detected in various tumors such as bladder cancer and gastric cancer, and it participates in the regulation of tumor cell proliferation. In this study, we detect the expression abundance of CENP-O mRNA in different ovarian cancer cells ( ES-2, A2780, Caov-3, OVCAR-3 and SK-OV-3). The biological function changes of cell proliferation and apoptosis were detected and the role of CENP-O in ovarian cancer cell proliferation and apoptosis was explored by knocking down the expression of CENP-O gene. The results showed that CENP-O gene was significantly expressed in 5 types of ovarian cancer cell lines. After knocking down the CENP-O gene, the proliferation and cloning ability of ovarian cancer cells decreased, and the apoptosis increased. This study indicates that CENP-O has the potential to be a molecular therapeutic target, and downregulating the expression of CENP-O gene can break the unlimited proliferation ability of cancer cells and promote their apoptosis, providing a foundation and new ideas for subsequent molecular mechanism research and targeted therapy.

Prognostic role of the peritoneal cancer index in ovarian cancer patients who undergo cytoreductive surgery: a meta-analysis.

Advanced-stage ovarian cancer is usually associated with peritoneal carcinomatosis. This study evaluates the prognostic role of the Peritoneal Cancer Index (PCI) in predicting the survival of patients with ovarian cancer. A literature search was conducted in electronic databases (Google Scholar, PubMed, Ovid, and Science Direct) and study selection was based on precise eligibility criteria. Random-effects meta-analyses were performed to estimate survival with low and high PCI scores and to pool hazard ratios (HR) of survival between lower and higher PCI scores. A total of 20 studies (2588 patients) were included. Median follow-up was 39 months [95%CI: 25, 54]. Complete cytoreduction rate was 80% [95% CI: 73, 87]. The median PCI score was 11.3 [95% CI: 9.9, 12.7]. Median survival was 56.7 months [95% CI: 45.2, 68.2] with below and 28.8 months [95% CI: 23.0, 34.6] with above any PCI cutoff. Most studies used PCI cutoffs between 10 and 20. The median progression-free survival was 23.7 months [95% CI: 16.5, 30.8] with below and 11.9 months [95% CI: 5.9, 17.9] with above any PCI cutoff. 5-year survival rates were 61.3% [95% CI: 49.9, 72.8] with PCI<10 cutoffs, 21.7% [95% CI: 11.6, 31.8] with PCI>10 cutoffs, 50.1% [95% CI: 39.0, 61.2] with PCI<20 cutoffs, and 21.7% [95% CI: 16.2, 27.1] with PCI>20 cutoffs. Pooled analysis of HRs showed that a higher PCI score was associated with worse survival in both univariate (HR 2.14 [95%CI: 1.63, 2.66]) and multivariate (HR 1.10 [95% CI: 1.02, 1.18]) analyses. In a set of studies that used varying PCI cutoffs, the PCI has been found to have a significant inverse association with the survival of patients with advanced ovarian cancer who underwent cytoreductive surgery.

Human umbilical cord mesenchymal stem cells-derived exosomes exert anti-inflammatory effects on osteoarthritis chondrocytes.

Inflammation of chondrocytes plays a critical role in the occurrence and development of osteoarthritis (OA). Recent evidence indicated exosomes derived from mesenchymal stem cells (MSCs-Exos) exhibit excellent anti-inflammatory ability in many troublesome inflammatory diseases including OA. In the present study, we aimed to explore the role of human umbilical cord-derived MSCs-Exos (hUC-MSCs-Exos) in treating the inflammation of chondrocytes and its related mechanisms. Ultracentrifugation was applied to isolate hUC-MSCs-Exos from the culture supernatant of hUC-MSCs. Two OA-like in vitro inflammation models of human articular chondrocytes induced with interleukin 1ß (IL-1ß) and co-incubation with macrophage utilizing transwell cell culture inserts were both used to evaluate the anti-inflammatory effects of hUC-MSCs-Exos. The mRNA sequencing of chondrocytes after treatment and microRNA (miRNA) sequencing of hUC-MSCs-Exos were detected and analyzed for possible mechanism analysis. The results of the study confirmed that hUC-MSCs-Exos had a reversed effect of IL-1ß on chondrocytes in the expression of collagen type II alpha 1 (COL2A1) and matrix metalloproteinase 13 (MMP13). The addition of hUC-MSCs-Exos to M1 macrophages in the upper chamber showed down-regulation of IL-1ß and tumor necrosis factor α (TNF-α), up-regulation of IL-10 and arginase1 (ARG1), and reversed the gene and protein expression of COL2A1 and MMP13 of the chondrocytes seeded in the lower chamber. The results of this study confirmed the anti-inflammatory effects of hUC-MSCs-Exos in the human articular chondrocytes inflammation model. hUC-MSCs-Exos may be used as a potential cell-free treatment strategy for chondrocyte inflammation in OA.

Curcumin as a therapeutic agent in cancer therapy: Focusing on its modulatory effects on circular RNAs.

Curcumin, a natural polyphenol compound, has been identified as an effective therapeutic agent against cancer that exerts its anti-tumor activities by up/downregulating signaling mediators and modulating various cellular processes, including angiogenesis, autophagy, apoptosis, metastasis, and epithelial-mesenchymal transition (EMT). Since almost 98% of genomic transcriptional production is noncoding RNAs in humans, there is evidence that curcumin exerts therapeutic effects through the alterations of noncoding RNAs in various types of cancers. Circular RNAs (circRNAs) are formed by the back-splicing of immature mRNAs and have several functions, including functioning as miRNA sponges. It has been shown that curcumin modulated various circRNAs, including circ-HN1, circ-PRKCA, circPLEKHM3, circZNF83, circFNDC3B, circ_KIAA1199, circRUNX1, circ_0078710, and circ_0056618. The modulation of these circRNAs targeted the expression of mRNAs and modified various signaling pathways and hallmarks of cancer. In this article, we reviewed the pharmacokinetics of curcumin, its anti-cancer activities, as well as the biology and structure of circRNAs. Our main focus was on how curcumin exerts anti-cancer functions by modulating circRNAs and their target mRNAs and pathways.

High expression of TARS is associated with poor prognosis of endometrial cancer.

INTRODUCTION: Endometrial cancer is the second largest and most common cancer in the world. It is urgent to explore novel biomarkers. METHODS: Data were obtained from The Cancer Genome Atlas (TCGA) database. The receiver operating characteristic (ROC) curves, Kaplan-Meier curves and Cox analysis, nomograms, gene set enrichment analysis (GSEA) were conducted. Cell proliferation experiments were performed in Ishikawa cell. RESULTS: TARS was significantly highly expressed in serous type, G3 grade, and deceased status. Significant association was between high TARS expression with poor overall survival (P = 0.0012) and poor disease specific survival (P = 0.0034). Significant differences were observed in advanced stage, G3 and G4, and old. The stage, diabetes, histologic grade, and TARS expression showed independent prognostic value for overall survival of endometrial cancer. The stage, histologic grade, and TARS expression showed independent prognostic value for disease specific survival of endometrial cancer. Activated CD4+ T cell, effector memory CD4+ T cell, memory B cell and type 2 T helper cell may participate in the high TARS expression related immune response in endometrial cancer. The CCK-8 results showed significantly inhibited cell proliferation in si-TARS (P < 0.05) and promoted cell proliferation in O-TARS (P < 0.05), confirmed by the colony formation and live/dead staining. CONCLUSION: High TARS expression was found in endometrial cancer with prognostic and predictive value. This study will provide new biomarker TARS for diagnosis and prognosis of endometrial cancer.

Exosomes derived from umbilical cord mesenchymal stem cells protect cartilage and regulate the polarization of macrophages in osteoarthritis.

Background: Osteoarthritis (OA) is one of the most common joint diseases and a major global public health concern. Mesenchymal stem cells (MSCs) have been widely used for the treatment of OA owing to their paracrine secretion of trophic factors, a phenomenon in which exosomes may play a major role. Here, we investigate the potential of exosomes from human umbilical cord-derived MSCs (hUC-MSCs-Exos) in alleviating OA. Methods: The hUC-MSCs-Exos were harvested from hUC-MSC-conditioned medium using ultracentrifugation. Rats with surgically-induced OA were intra-articularly injected with hUC-MSCs-Exos. The effect of hUC-MSCs-Exos in repairing osteoarticular cartilage was assessed using hematoxylin and eosin (HE) staining, safranin-O and fast green staining and immunohistochemistry. The in vitro experiments were further carried out to verify the therapeutic effect. The effects of hUC-MSCs-Exos on the proliferation and migration of human chondrocytes were evaluated using the cell counting kit-8, EdU-555 cell proliferation kit, and transwell assays. Annexin V-FITC/PI staining were used to evaluate the effect of exosomes on chondrocyte apoptosis. An in vitro model of human articular chondrocytes treated with interleukin 1 beta (IL-1ß) was used to evaluate the effects of exosomes, analyses involved using quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and western blotting. The role of hUC-MSCs-Exos in macrophage polarization was examined in the monocyte cell line, Tohoku Hospital Pediatrics-1 (THP-1) by qRT-PCR and immunofluorescence. Results: The results showed that hUC-MSCs-Exos prevented severe damage to the knee articular cartilage in the rat OA model. We confirmed the high efficacy of hUC-MSCs-Exos in promoting chondrocyte proliferation and migration and inhibiting chondrocyte apoptosis. Additionally, hUC-MSCs-Exos could reverse IL-1ß-induced injury of chondrocytes and regulate the polarization of macrophages in vitro. Conclusions: There is potential for hUC-MSCs-Exos to be used as a treatment strategy for OA.

Retraction notice to "MicroRNA-27a regulates the proliferation, chemosensitivity and invasion of human ovarian cancer cell lines by targeting Cullin 5" [YABBI 688C (2019) 9-15 / 7995].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The entire 'Reason' text must be identical to that in the XML version (Box 6).

Regulatory effects of lncRNAs and miRNAs on the crosstalk between autophagy and EMT in cancer: a new era for cancer treatment.

PURPOSE: Autophagy and EMT (epithelial-mesenchymal transition) are the two principal biological processes and ideal therapeutic targets during cancer development. Autophagy, a highly conserved process for degrading dysfunctional cellular components, plays a dual role in tumors depending on the tumor stage and tissue types. The EMT process is the transition differentiation from an epithelial cell to a mesenchymal-like cell and acquiring metastatic potential. There is evidence that the crosstalk between autophagy and EMT is complex in cancer. In recent years, more studies have shown that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in autophagy, EMT, and their crosstalk. Therefore, accurate understanding of the regulatory mechanisms of lncRNAs and miRNAs in autophagy, EMT and their interactions is crucial for the clinical management of cancers. METHODS: An extensive literature search was conducted on the Google Scholar and PubMed databases. The keywords used for the search included: autophagy, EMT, crosstalk, lncRNAs, miRNAs, cancers, diagnostic biomarkers, and therapeutic targets. This search provided relevant articles published in peer-reviewed journals until 2021. Data from these various studies were extracted and used in this review. RESULTS: The results showed that lncRNAs/miRNAs as tumor inhibitors or tumor inducers could regulate autophagy, EMT, and their interaction by regulating several molecular signaling pathways. The lncRNAs/miRNAs involved in autophagy and EMT processes could have potential uses in cancer diagnosis, prognosis, and therapy. CONCLUSION: Such information could help find and develop lncRNAs/miRNAs based new tools for diagnosing, prognosis, and creating anti-cancer therapies.

lncRNA HEIH accelerates cell proliferation and inhibits cell senescence by targeting miR-3619-5p/CTTNBP2 axis in ovarian cancer.

OBJECTIVE: Epithelial ovarian cancer is the most lethal malignancy in gynecology. Numerous studies have confirmed that long noncoding RNAs (lncRNAs) are abnormally expressed in ovarian cancer and are closely associated with the cell proliferation and senescence in cancers. However, the role and underlying molecular mechanism of long noncoding RNA high expression in hepatocellular carcinoma (HEIH) in ovarian cancer remain unknown. METHODS: Experiments including Real-time quantitative polymerase chain reaction, RNA immunoprecipitation, luciferase reporter, Fluorescence in situ hybridization, western blot, colony formation assays, ß-galactosidase senescence assay, cell apoptosis, proliferation, invasion, and migration assays were applied to investigate the role of HEIH in ovarian cancer. The data were expressed as the mean ±â€Šstandard deviation. Student t test was used to compare the data between two groups. The one-way analysis of variance was applied to compare the data among multiple groups with Tukey post hoc test. All experiments were repeated three times. P < 0.05 was considered statistically significant. RESULTS: Herein, HEIH expression was found to be up-regulated in ovarian cancer tissues (n = 25; twofold higher than normal tissues, P < 0.05) and cell lines (sixfold higher than normal ovarian epithelial cell line on average, P < 0.05), and high HEIH expression predicted poor prognosis (survival rate is about 25% after 40 mo; P < 0.05). Moreover, we found that HEIH accelerated proliferation, migration, and invasion, whereas inhibited cell senescence in ovarian cancer (P < 0.05). In mechanism, HEIH was confirmed to serve as a sponge for miR-3619-5p, and miR-3619-5p counteracted HEIH-mediated regulation of ovarian cancer (P < 0.05). Besides, cortactin-binding protein 2 (CTTNBP2) was found to be the downstream target of miR-3619-5p. Rescue assays validated that CTTNBP2 up-regulation significantly reversed the inhibitory effects of HEIH knockdown on ovarian cancer progression (P < 0.05). Furthermore, we found that HEIH facilitated tumor growth in vivo by regulating CTTNBP2 expression (P < 0.05). CONCLUSIONS: In conclusion, our research revealed that HEIH accelerated cell proliferation, migration and invasion, whereas inhibited cell senescence in ovarian cancer via targeting the miR-3619-5p/CTTNBP2 axis. These findings may be valuable for finding new therapeutic targets to improve ovarian cancer treatment.

Outcome evaluation of neoadjuvant chemotherapy in patients with stage IB2 or IIA cervical cancer: a retrospective comparative study.

BACKGROUND: To study the benefits of neoadjuvant chemotherapy (NACT) in addition to surgical resection and postoperative chemoradiotherapy (CRT) in patients with stage IB2 or IIA cervical cancer. METHODS: We retrospectively analyzed 363 patients with stage IB2 or IIA cervical cancer that received the surgical resection and postoperative CRT with or without NACT at the Second Hospital of Jilin University between February 2014 and December 2016. We chose mortality as the primary outcome, and the clinical deterioration as secondary outcome. These outcomes were compared between two groups of patients with or without NACT by univariate or multivariate logistic regression analysis. RESULTS: Among the 363 identified patients, 114 patients were in the neoadjuvant group and 249 patients in the non-neoadjuvant group. The median follow-up period was 36.4 months, ranging from 28 to 55 months. There were statistically significant differences in the tumor differentiation, clinical stages, vascular tumor thrombus, and postoperative radiotherapy between these two group patients. After adjusting for these variables, patients in the neoadjuvant group had a statistically significantly lower survival rate than those in the non-neoadjuvant group within one year after the treatment, but this difference disappeared at the 3-year follow-up period. Also, more patients in the neoadjuvant group experienced clinical deterioration at the 3-year follow-up period. CONCLUSIONS: NACT did not show significant benefits in mortality and clinical deterioration in patients with stage IB2 or IIA cervical cancer.

Generation of two ERF gene knockout human embryonic stem cell lines using CRISPR/Cas9 system.

Human ERF gene is a transcription factor involved in development, trophoblast differentiation, apoptosis, and cancer progress. To further understand the exact roles of ERF in these processes, here we report that establishment of two ERF knockout human embryonic stem cell (hESC) lines by CRISPR/Cas9 mediated gene targeting. These cell lines exhibited classical hESC morphology and normal karyotype, and highly expressed pluripotent markers, and had differentiation potential in vitro. These cell lines provide good materials to understand the roles of ERF in development, trophoblast differentiation and craniosynostosis for further studies.

Neoadjuvant chemotherapy does not improve the prognosis and lymph node metastasis rate of locally advanced cervical squamous cell carcinoma: A retrospective cohort study in China.

Locally advanced cervical carcinoma has a poor prognosis. Neoadjuvant chemotherapy (NACT) can reduce tumor size and improve tumor resection rate, but its use in large locally advanced cervical carcinoma is controversial. This study aimed to evaluate the treatment and prognosis of NACT in patients with cervical carcinoma stage IB2 or IIA2.This was a retrospective cohort study of patients who underwent type-C radical surgery and pelvic lymphadenectomy due to cervical carcinoma stage IB2/IIA2 between 2/2014 and 12/2016 at the Second Hospital of Jilin University. The patients were grouped according to whether they received NACT (paclitaxel and a platinum salt) or not. Overall survival (OS) and progression-free survival (PFS) were compared between the 2 groups.Of the 144 patients, 60 (41.7%) received NACT. A total of 119 patients underwent postoperative radiation therapy, of which 97 received radiation therapy alone and 22 received concurrent chemoradiotherapy. The adverse reactions in the NACT group were mainly hematologic toxic reactions, but were tolerated. No grade ≥III adverse reactions were observed. NACT did not significantly affect the PFS (P = .453) and OS (P = .933) between the 2 groups. No factor was found to be independently associated with OS or PFS (all P > .05).Compared with patients who underwent surgery with/without radiotherapy and/or chemotherapy, NACT using paclitaxel and a platinum salt does not improve the prognosis and lymph node metastasis rate of locally advanced cervical carcinoma in Chinese patients.

Prognostic value of lymphovascular space invasion in patients with early stage cervical cancer in Jilin, China: A retrospective study.

The metastasis of cervical carcinoma is associated with the lymphovascular spread. The primary objective of the present study was to determine the prognostic value of lymphovascular space invasion (LVSI) in patients with early-stage cervical cancer in Jilin, China.In this retrospective cohort study, patients with early-stage cervical cancer (stage IB-IIA) at the Second Hospital of Jilin University from February 2014 to December 2016 were included in the analysis. All included participants underwent radical hysterectomy with pelvic lymphadenectomy. LVSI was identified by hematoxylin and eosin (H&E) staining. The primary outcomes are overall survival (OS) and progression-free survival (PFS). Kaplan-Meier curves were used to calculate the patient's survival. Survival was compared using the log-rank test, while risk factors for the prognosis were assessed by Cox regression analysis.The incidence of LVSI was positively associated with the depth of stromal invasion (P = .009) and lymph node metastasis (LNM, P < .001). LVSI is an independent factor that affects OS (P = .009) and PFS (P = .006) in patients with early stage cervical cancer. LNM status is an independent factor that affects postoperative OS (P = .005).The incidence of lymphatic vessel infiltration is positively associated with the depth of stromal invasion and LNM. LVSI is an independent risk factor for the prognosis of early cervical cancer. The results suggest that further large-scale studies are needed to improve the treatment for patients with LVSI.

Kaempferol exerts anti-proliferative effects on human ovarian cancer cells by inducing apoptosis, G0/G1 cell cycle arrest and modulation of MEK/ERK and STAT3 pathways.

PURPOSE: Ovarian cancer causes significant mortality in women and is one of the most prevalent types of gynaecological cancer world over. Ovarian cancer is often diagnosed at advanced stages and the currently used anticancer drugs produce several adverse effects. Herein, we examined the anticancer effects of a natural flavonoid Kaempferol against a panel of ovarian cancer cells. METHODS: WST-1 and colony formations assays were used to examine the anti-proliferative effects of Kaempferol. AO/EB, DAPI and annexin V/PI staining assays were used to check apoptosis. Cell cycle analysis was performed by flow cytometry and western blotting was used to check the expression of the proteins. RESULTS: The results showed that Kaempferol could inhibit the growth of ovarian cancer cells with IC50 ranging between 25 to 50 µM. However, the cytotoxic effects of Kaempferol were comparatively negligible against the normal SV40 cells with an IC50 of >120 µM. Exploration of the mechanism of action revealed that Kaempferol exerts growth inhibitory effects on the OVACAR-3 ovarian cancer cells by apoptotic cell death. This was also accompanied with upregulation of apoptotic proteins such as caspase 3, 8 and 9 and Bax. Kaempferol also induced arrest of the OVACAR-3 cells at the G2/M check point of the cell cycle. In addition, Kaempferol could also inhibit the MEK/ERK and STAT3 signal transduction pathways. CONCLUSION: Taken together, these results suggest that Kaempferol exerts potent anticancer effects on ovarian cancer cells and may prove useful in the management of ovarian cancer.

Lactobacillus bulgaricus improves antioxidant capacity of black garlic in the prevention of gestational diabetes mellitus: a randomized control trial.

Objectives:Lactobacillus bulgaricus may improve antioxidant capacity of black garlic in the prevention of gestational diabetes mellitus (GDM).Methods: Black garlic was prepared with or without L. bulgaricus Volatile and polysaccharides were analyzed by using LC-MS, Fourier Transform infrared (FTIR) and 13C nuclear magnetic resonance (NMR). The study design was parallel randomized controlled trial and 226 GDM patients were randomly assigned into BG (black garlic and L. bulgaricus) and CG (black garlic) groups, and allocation ratio was 1:1. The treatment duration was 40 weeks. Fasting blood glucose (FBG) and 1- and 2-h blood glucose (1hBG and 2hBG) after oral glucose tolerance test (OGTT) were detected. Antioxidant function of black garlic was determined by measuring plasma malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and total antioxidant capacity (T-AOC) in GDM patients. The comparison between two groups was made using two independent samples t test.Results: The intake of nutrients was similar between two groups (P>0.05). L. bulgaricus promoted the transformation of the glucopyranoside to glucofuranoside. L. bulgaricus increased the abilities of black garlic for scavenging hydroxyl radicals, 2,2'-azino-bis (3-ethylbenzenthiazoline-6-sulfonic) acid (ABTS) and DPPH free radicals. L. bulgaricus reduced the levels of FBG, 1hBG and 2hBG, and incidence of perinatal complications (P<0.01). Plasma MDA level in the BG group was lower than in the CG group, whereas the levels of SOD, GSH-PX and T-AOC in the BG group were higher than in the CG group (P<0.01).Conclusions:L. bulgaricus improves antioxidant capacity of black garlic in the prevention of GDM.

MicroRNA-27a regulates the proliferation, chemosensitivity and invasion of human ovarian cancer cell lines by targeting Cullin 5.

Reports suggest that microRNAs have implications in the development of several diseases including cancer. It is therefore believed that miRs may act as therapeutic targets for cancer treatment. The treatment of ovarian cancer is mainly obstructed by lack of biomarkers and efficient drug targets. Against this backdrop, this study was undertaken to unveil the therapeutic implications of miR-27a in ovarian cancer. The results showed that the expression of miR-27a was significantly elevated in ovarian cancer tissues and cell lines. Inhibition of miR-27a expression resulted in the decrease of proliferation rate and colony formation potential of the SK-OV-3 and OVACAR-3 cells via G2/M arrest. The miR-27a inhibition triggered G2/M arrest of SK-OV-3 and OVACAR-3 cells was accompanied with depletion of cyclin A and B1 expression levels. TargetScan analysis together with dual reporter assay revealed that miR-27a exerts its effects via modulation of CUL5 expression. The CUL5 was shown to be suppressed in the ovarian cancer tissues and cell lines and suppression of miR-27a expression caused upregulation of CUL5 expression. Overexpression of CUL5 caused inhibition of SK-OV-3 and OVACAR-3 cell proliferation via induction of G2/M arrest, similar to that of miR-27a inhibition. Interestingly, CUL5 overexpression reversed the effects of miR-27a inhibition on the viability of SK-OV-3 cells. Finally, the suppression of miR-27a could enhance the chemosensitivity of the SK-OV-3 cells to cisplatin and docetaxel anticancer drugs and also decreased their migration and invasion. The findings of this study revealed that miR-27a suppression inhibits the growth, chemosensitivity and invasion of ovarian cancer and may prove beneficial in the ovarian cancer management.

Thiophenol-formaldehyde triazole causes apoptosis induction in ovary cancer cells and prevents tumor growth formation in mice model.

In the present study a library of thiophenol-formaldehyde-triazole (TFT) derivatives was synthesized and screened against CAOV3, CAOV4 and ES-2 ovary cancer cell lines. Initial screening revealed that five-compounds 5a, 5b, 5j, 5h and 5i inhibited the viability of tested cell lines. Analysis of apoptosis revealed that increase in compound 5a (most active) concentration from 0.25 to 2.0 µM enhanced apoptotic cell proportion. Transwell assay showed reduction in invasive potential of CAOV3 cells on treatment with compound 5a. In wound healing assay increasing the concentration of compound 5a from 0.5 to 2.0 µM caused a significant (P < 0.05) decrease in the migration potential. Western blotting showed that compound 5a treatment markedly decreased the level of matrix metalloproteinase (MMP)-2 and -9 in CAOV3 cells. Treatment of CAOV3 cells with compound 5a caused a marked decrease in Focal Adhesion Kinase (FAK) activation. Tumor growth was inhibited in the compound 5a treated mice markedly than those of untreated group. The tumor metastasis to liver, intestine, spleen and peritoneal cavity was markedly decreased in mice treated with 10 mg/kg dose of compound 5a. Examination of Von Willebrand factor (vWF) expression in liver, intestinal and pulmonary lesions showed a marked decrease in the compound 5a-treated mice. The infiltration of macrophages in the metastatic lesions showed a significant decrease in compound 5a-treated mice. In conclusion, the compound 5a inhibited ovary cancer cell viability and induced apoptosis through decrease in expression of vWF and metalloproteinase, suppression of FAK activation and decrease in infiltration of macrophages. The compound 5a therefore can be investigated further for the treatment of ovary cancer.

MicroRNA-34 suppresses proliferation of human ovarian cancer cells by triggering autophagy and apoptosis and inhibits cell invasion by targeting Notch 1.

Ovarian cancer is one the prevalent cancers in women and is responsible for 5% of all the cancer related mortalities in women. Owing to late diagnosis, frequent relapses, side effects of chemotherapy, development of drug resistance, there is pressing need to screen out novel and effective treatment options. Accumulating evidences suggest that miRNAs may prove essential therapeutic targets for the treatment of cancer. This study was designed to investigate the role and therapeutic potential of miR-34 in ovarian cancer. It was found that miR-34 is significantly downregulated in ovarian cancer cell lines. Overexpression of miR-34 causes significant decrease in the proliferation of OVACAR-3 ovarian cancer cells via activation of apoptosis and autophagy. The miR-34 overexpression was concomitant with upsurge of apoptosis related proteins (Bax) and the autophagy associated protein (LC3 II and p62). TargetScan analysis showed Notch 1 to be the main target of miR-34 in OVACAR-3 cells which was further validated by luciferase reporter assay. The qRT-PCR results showed Notch 1 to be 3.2-4.1 fold higher in the ovarian cancer cell lines relative to the non-cancerous cells. Nonetheless, miR-34 overexpression in OVACAR-3 cells resulted in the post-transcriptional suppression of Notch 1 expression. Silencing of Notch 1 also caused inhibition of OVACAR-3 cell proliferation via induction of apoptosis and autophagy. Overexpression of Notch 1 could partially rescue the effects of miR-34 overexpression on the proliferation of OVACAR-3 cells. Moreover, overexpression of miR-34 causes significant inhibition of the invasion of the OVACAR-3 cells. The findings of the present study indicate the tumor suppressive role of miR-34 in ovarian cancer and may therefore prove to be a potential therapeutic target.

Cod-Liver Oil Improves Metabolic Indices and hs-CRP Levels in Gestational Diabetes Mellitus Patients: A Double-Blind Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of cod-liver oil on metabolic status and high-sensitivity C-reactive protein (hs-CRP) in patients with gestational diabetes mellitus (GDM). METHODS: This study was a randomized, double-blinded, placebo-controlled trial with the allocation ratio of 1 : 1. The contents of EPA and DHA in cod-liver oil were measured using a gas chromatograph. A total of 550 GDM patients were randomly divided into the intervention group (cod-liver oil) and the control group (placebo, mineral oil), and both groups were given regular dietary care. Glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), lipid profiles, homeostatic model assessment insulin resistance (HOMA-IR), and hs-CRP were measured. Primary outcomes were different in HbA1c, FPG, 2hPG, and HOMA-IR between the two groups after 4-week randomization. Secondary outcomes were the blood glucose levels and perinatal complications (pregnancy-induced hypertension, polyhydramnios, premature delivery, postpartum hemorrhage, postpartum infection, premature rupture of membranes, and cesarean section) between the two groups before and after 12-16 weeks of cod-liver oil intervention from middle pregnancy to late pregnancy. RESULTS: EPA and DHA were the main components of cod-liver oil with 76 mg/mL and 150 mg/mL, respectively. There was no significant difference for primary outcomes in the levels of HbA1c, FPG, 2hPG, HOMA-IR, and lipid profiles between the two groups (P > 0.05). For the secondary outcomes, the levels of HbA1c, FPG, 2hPG, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol ratio (LDL-C), HOMA-IR, and hs-CRP in the intervention group were significantly lower than those in the control group (P < 0.05). The incidence of perinatal complications in the intervention group was lower than that in the control group too (P < 0.05). CONCLUSIONS: Cod-liver oil consumption effectively reduced the levels of blood glucose, lipid levels, hs-CRP, and HOMA-IR and the incidence of perinatal complications.