Retraction Notice to: lncRNA PVT1/MicroRNA-17-5p/PTEN Axis Regulates Secretion of E2 and P4, Proliferation, and Apoptosis of Ovarian Granulosa Cells in PCOS.

[This retracts the article DOI: 10.1016/j.omtn.2020.02.007.].

ß-Edorphin predict pregnancy outcome of PCOS and DOR women after IVF-ET.

PURPOSE: The present study aims to explore whether ß-EP in serum (sß-EP) and follicular fluid (ffß-EP) could predict the in vitro fertilization (IVF) outcomes of patients with polycystic ovary syndrome (PCOS) and diminished ovarian reserve (DOR). METHODS: 90 PCOS women, 50 DOR women, and 100 women with normal ovarian function (control group), who were all undergoing an IVF-embryo transfer trial, were included in the study. Biochemical characteristics, anti-Mullerian hormone (AMH), sß-EP, ffß-EP, embryo formation, and pregnancy indicators were assessed in all women. The correlations of AMH and ß-EP with oocyte quality were analyzed. Population-based and age-category stratified receiver operating characteristic (ROC) curve analysis of AMH and ß-EP for predicting pregnancy and live birth were performed. RESULTS: Compared with the control group, the PCOS group had higher antral follicle count, testosterone, luteinizing hormone, AMH, sß-EP, and ffß-EP, which were lower in the DOR group. Meanwhile, the PCOS and DOR groups had higher cycle cancellation and miscarriage rates, and lower high quality embryo numbers. Correlation analysis showed that the oocyte quality were positively correlated with AMH, sß-EP, and ffß-EP. The population-based and age-stratified ROC curve analysis showed that sß-EP and ffß-EP had high sensitivity and specificity to predict pregnancy and live birth. Meanwhile, age-stratified AMH enhanced the sensitivity for prediction of live birth after IVF. CONCLUSION: sß-EP and ffß-EP are different among women with PCOS, DOR, and normal ovarian function. ß-EP can be used as a good predictor of clinical pregnancy and live birth after IVF.

High Regioselectivity Production of 5-Cyanovaleramide from Adiponitrile by a Novel Nitrile Hydratase Derived from Rhodococcus erythropolis CCM2595.

5-Cyanovaleramide (5-CVAM) is an important intermediate of a herbicide and chemical raw material. Herein, we found a novel nitrile hydratase from the strain Rhodococcus erythropolis CCM2595, exhibiting high regioselectivity with higher substrate specificity toward dinitriles than mononitriles. In the past, the strain was shown to degrade only phenol, hydroxybenzoate, p-chlorophenol, aniline, and other aromatic compounds. In our study, 20 mM adiponitrile was completely consumed within 10 min with 95% selectivity to 5-CVAM and 5% selectivity to adipamide. In addition to its high regioselectivity, our recombinant Escherichia coli showed a higher substrate tolerance of up to 200 mM adiponitrile even after 3 h when compared with two reported strains with their cyano-tolerance concentrations of up to 100 mM, which is considered to be the highest cyano-tolerance. Such a robust biocatalyst is a desirable attribute of a biocatalyst intended for use in commercial applications of 5-CVAM.

lncRNA PVT1/MicroRNA-17-5p/PTEN Axis Regulates Secretion of E2 and P4, Proliferation, and Apoptosis of Ovarian Granulosa Cells in PCOS.

Recently, the roles of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) were identified in polycystic ovary syndrome (PCOS). In the present study, we investigated the role of the lncRNA PVT1/miR-17-5p/PTEN axis in PCOS ovarian granulosa cells. Expression of PVT1, miR-17-5p and PTEN in PCOS ovarian granulosa cells and follicular fluid was detected, and homeostatic model assessment of insulin resistance (HOMA-IR) and the levels of fasting plasma glucose (FPG), fasting insulin (FINS), and sex hormones were assessed. Then, the proliferation, apoptosis, and colony formation ability of ovarian granulosa cells were evaluated. The binding relationship between PVT1 and miR-17-5p as well as the target relationship between miR-17-5p and PTEN were determined by bioinformatics analysis, luciferase activity assay, RNA-induced silencing complex assay, and RNA pull-down assay. The levels of sex hormone-binding globulin and follicle-stimulating hormone were abated and the levels of luteinizing hormone, testosterone, FINS, FPG, and HOMA-IR were increased in PCOS serum. PVT1 and PTEN were overexpressed and miR-17-5p was reduced in PCOS ovarian granulosa cells and follicular fluid. Overexpressed miR-17-5p and inhibited PVT1 could decelerate apoptosis while accelerating colony formation ability and proliferation of ovarian granulosa cells in PCOS. Moreover, overexpression of PVT1 and reduced miR-17-5p could reverse these results. There existed target relation among PVT1, miR-17-5p, and PTEN, and PVT1 could inhibit miR-17-5p, thereby elevating PTEN. Our study suggests that inhibited PVT1 and overexpressed miR-17-5p result in downregulation of PTEN and promotion of cell proliferation, as well as inhibition of apoptosis of ovarian granulosa cells in PCOS.

LncRNA LOXL1-AS1 promotes endometrial cancer progression by sponging miR-28-5p to upregulate RAP1B expression.

BACKGROUND: Increasing lncRNAs are found to be involved in the biological process of multiple cancer types. Herein, we aimed to reveal the role of LOXL1-AS1 in endometrial cancer (EC) progression. METHODS: Tumor and corresponding normal tissues were obtained from EC patients. Si-LOXL1-AS1 and miR-28-5p inhibitor were transfected to downregulate the expressions of LOXL1-AS1 and miR-28-5p, while miR-28-5p mimics were used to upregulate the miR-28-5p expression. CCK-8 and colony assays were applied to estimate the cell proliferation. Flow cytometry was performed to measure the cell apoptosis. Wound healing and transwell assays were conducted to assess the cell migration and invasion abilities. Informatics analysis was used to explore the relationship among LOXL1-AS1, miR-28-5p and RAP1B. RESULTS: LOXL1-AS1 was found markedly up-regulated in EC tissues and cell lines. LOXL1-AS1 knockdown displayed evident suppression in cell proliferation, migration and invasion, as well as promotion in cell apoptosis. Moreover, the LOXL1-AS1 induced regulatory effects on EC cells were partially reversed by miR-28-5p inhibitor. Mechanistically, LOXL1-AS1 competitively bond to miR-28-5p, resulting in upregulation of RAP1B. Additionally, in vivo study confirmed the findings discovered in vitro. CONCLUSIONS: In summary, LOXL1-AS1 exerted oncogenic roles in EC progression by sponging miR-28-5p and thereby upregulating RAP1B. This finding might provide potential targets for EC therapy.

Ortho-Topolin Riboside Induced Differentiation through Inhibition of STAT3 Signaling in Acute Myeloid Leukemia HL-60 Cells

Objective: We previously demonstrated that ortho-topolin riboside (oTR) as a naturally occurring cytokinin secreted from Populus × robusta has great potential anticancer effects via the mitochondrial apoptotic pathway and endoplasmic reticulum stress pathway. In the present study, we reveal that oTR induced the differentiation of acute myeloid leukemia (AML) HL-60 cells, which represent the M2 subtype of AML. Materials and Methods: After the incubation of HL-60 cells with oTR, its effect was analyzed with cell viability assay, Wright-Giemsa staining, CD11b protein expression analysis, western blot analysis, and polymerase chain reaction. Results: We found that oTR arrested the cell cycle at the S phase, upregulated the expression of myeloid surface marker CD11b, reduced the nuclear cytoplasmic ratio, and altered the horseshoe shape of nuclei, as evidenced by Wright-Giemsa staining. Furthermore, we found that the protein level of phosphorylated STAT3 was decreased when cells were treated with oTR, while phosphorylated STAT1 was activated. Moreover, the protein level of phosphorylated STAT3 and its upstream kinase, Janus kinase 2, were also inhibited when cells were treated with oTR after increased time. Additionally, the levels of phosphorylated SHP-1 were increased while phosphorylated SHP-2 was decreased. Conclusion: Collectively, our data indicate a differentiation-induced mechanism underlying the inhibition of STAT3 signaling upon treatment with oTR. Therefore, oTR may constitute a novel differentiation-induced therapeutic for use in clinical treatment of AML.

Knockdown of pleiotrophin increases the risk of preeclampsia following vitrified-thawed embryo transfer.

Preeclampsia (PE) in pregnancy is associated with vitrified-thawed embryo transfer. Pleiotrophin (PTN) is important in inflammation via its receptors. The aim of the present study was to determine the effect of PTN on the risk of PE following embryo transfer. An enzyme-linked immunosorbent assay was performed to determine the levels of tumor necrosis factor (TNF)-α and PTN in serum. The knockdown of PTN was conditionally induced by tamoxifen (tax) treatment. The tail-cuff method and Bradford assay were used to monitor blood pressure and the level of urine protein, respectively. The expression patterns of PTN, receptor protein tyrosine phosphatase ß/ζ, (RPTPß/ζ), syndecan-1 (SDC1), syndecan-3 (SDC3) and anaplastic lymphoma kinase (ALK) were determined by immunohistochemistry (IHC). Western blot analysis was performed to evaluate the expression level of PTN and its receptors. The risk of PE was elevated following embryo transfer in clinical and in the tax/PTN-/- group. It was found that the level of PTN increased when pregnancy progressed in normal conditions, however, the level of PTN was reduced in the PE mice. In addition, increases in TNF-α, blood pressure and urine protein were more marked in the PE mice that lacked PTN, compared with those in other PE mice. In addition, overlapping expression of PTN and its receptors in villous mesenchyme and fetal macrophages were identified using an IHC assay. However, the positive staining of PTN and its receptors was weaker or even absent in the PE mice. The protein level of RPTPß/ζ was lower in the PE mice that lacked PTN than that in the other PE mice. The knockdown of PTN increased the risk of PE following vitrified-thawed embryo transfer, in which its receptors, particularly RPTPß/ζ, may be involved.

Resveratrol protects Leydig cells from nicotine-induced oxidative damage through enhanced autophagy.

Some studies have revealed that nicotine can damage the male reproductive system through various means including oxidative stress, which is a primary factor in the pathogenesis of male infertility. The strong anti-oxidative capacity of resveratrol has been demonstrated previously, but its role in the context of male reproduction remains inconclusive. To explore the biological role of resveratrol in protecting male reproductive function and the potential underlying mechanism, nicotine-induced Leydig cells were used as a cell model of oxidative damage. The data showed that resveratrol treatment increased cell viability, SOD activity and anti-apoptotic activity in nicotine-stressed Leydig cells. This effect was accompanied by the upregulation of autophagy, which was illustrated by MDC-LysoTracker red staining. Moreover, pretreating with 3-methyladenine (3-MA), an autophagy inhibitor, attenuated resveratrol-induced Leydig cells autophagy and promoted apoptosis. Apart from this, resveratrol enhanced AMPK phosphorylation but reduced mTOR phosphorylation. Subsequently, upon inhibiting AMPK phosphorylation by AMPK inhibitors, Leydig cell autophagy induced by resveratrol was obviously abolished. In conclusion, resveratrol may exert its cytoprotective role against oxidative injury by the activation of autophagy via AMPK/mTOR pathway.