Angiopoietin4 (ANGPT4) expression and potential mechanisms in carcinogenesis: current achievements and perspectives.

Angiopoietin4(ANGPT4) which plays a significant role in endothelial cell proliferation, survival, angiogenesis and expansion in tumors and other pathological states is a significant regulator of tumor angiogenesis. ANGPT4 expression is enhanced in many cancer cells. For example, the overexpression of ANGPT4 promotes the formation, development and progress of lung adenocarcinoma, glioblastoma and ovarian cancer. Related studies show that ANGPT4 encourages the proliferation, survival and invasion of tumor cells, while promoting the expansion of the tumor vascular system and affecting the tumor immune microenvironment. ANGPT4 can also promote carcinogenesis by affecting the ERK1/2, PI3K/AKT and other signal pathways downstream of tyrosine kinase with immunoglobulin-like and EGF-like domains 2(TIE2) and TIE2. Therefore, ANGPT4 may be a potential and significant biomarker for predicting malignant tumor progression and adverse outcomes. In addition, inhibition of ANGPT4 may be a meaningful cancer treatment. This paper reviews the latest research results of ANGPT4 in preclinical research, and emphasizes its role in carcinogenesis. Additional research on the carcinogenic function of ANGPT4 could provide new insights into cancer biology and novel methods for cancer diagnosis and treatment.

Endometrial transcriptome profiling of patients with recurrent implantation failure during hormone replacement therapy cycles.

Background: The molecular mechanisms underlying window of implantation (WOI) displacement in patients with recurrent implantation failure (RIF) remain unclear. This study aims to explore the transcriptomic signatures of endometrium with normal and displaced WOIs and to identify the causes of endometrial receptivity (ER) abnormalities and WOI displacement in RIF patients. Methods: In this study, 40 RIF patients were recruited and underwent personalized embryo transfer (pET) guided by the predicted results of endometrial receptivity diagnosis (ERD) model. Transcriptome analysis of endometrium from patients with clinical pregnancies after pET was performed to identify differentially expressed genes (DEGs) associated with WOI displacement. Gene expression data from HRT and natural cycle endometrium were compared to identify specific gene expression patterns of ER-related genes during WOI. Results: The ERD results indicated that 67.5% of RIF patients (27/40) were non-receptive in the conventional WOI (P+5) of the HRT cycle. The clinical pregnancy rate in RIF patients improved to 65% (26/40) after ERD-guided pET, indicating the effectiveness of transcriptome-based WOI prediction. Among the 26 patients with clinical pregnancy, the gene expression profiles of P+5 endometrium from advanced (n=6), normal (n=10) and delayed (n=10) WOI groups were significantly different from each other. Furthermore, 10 DEGs identified among P+5 endometrium of 3 groups were involved in immunomodulation, transmembrane transport and tissue regeneration, which could accurately classify the endometrium with different WOIs. Additionally, a large number of ER-related genes showed significant correlation and similar gene expression patterns in P+3, P+5, and P+7 endometrium from HRT cycles and LH+5, LH+7, and LH+9 endometrium from natural cycles. Conclusion: Our study shows that ER-related genes share similar gene expression patterns during WOI in both natural and HRT cycles, and their aberrant expression is associated with WOI displacements. The improvement of pregnancy outcomes in RIF patients by adjusting ET timing according to ERD results demonstrates the importance of transcriptome-based endometrial receptivity assessment and the clinical efficiency of ERD model.

The clinical efficiency of transcriptome-based endometrial receptivity assessment (Tb-ERA) in Chinese patients with recurrent implantation failure (RIF): A study protocol for a prospective randomized controlled trial.

Background: Today, approximately 10% of participants in assisted reproductive technology (ART) are defined as having recurrent implantation failure (RIF). Recent studies show that endometrial receptivity array can improve pregnancy and implantation rates by nearly 20% in women with RIF. However, these studies are limited, with little published data in the Chinese population. Recently, we have established a transcriptome-based endometrial receptivity assessment (Tb-ERA) method of predicting the endometrial window of implantation (WOI) using transcriptome-profiling data of different phases of the menstrual cycle from healthy fertile Chinese women by RNA-Seq. It is meaningful to conduct a randomized controlled trial (RCT) to assess the clinical efficiency of Tb-ERA in Chinese patients with RIF. Methods: In this RCT, a total of 200 RIF patients will be recruited and randomized into 2 groups. Patients in the Tb-ERA group will undergo a Tb-ERA test, after which embryo transfer time will be adjusted according to Tb-ERA results and embryo transfer will be performed again in the next cycle. Patients in the control group will not receive any interventions until the next transfer cycle. We will perform statistical analysis on both groups at the primary endpoint (clinical-pregnancy rate) and at secondary endpoints (rate of WOI displacement, embryo implantation, biochemical pregnancy, early abortion, and ectopic pregnancy). Implications: This study aims to evaluate the effectiveness of our Tb-ERA test in Chinese RIF patients and to determine that whether Tb-ERA could improve the clinical-pregnancy rate in these RIF patients. Trial registration: NCT04497558, registered August 4, 2020.

Transcriptomic analysis of endometrial receptivity for a genomic diagnostics model of Chinese women.

OBJECTIVE: To define the transcriptomic signature with respect to human endometrial receptivity in Chinese women by next-generation sequencing and to develop a more refined and customized bioinformatic predictive method for endometrial dating in Chinese women. DESIGN: Randomized. SETTING: A tertiary hospital-based reproductive medicine center. PATIENT(S): Ninety healthy, fertile Chinese women. INTERVENTION(S): Human endometrial biopsies. MAIN OUTCOME MEASURE(S): Gene expression of endometrial biopsies. RESULT(S): Ninety endometrial samples from healthy Chinese women during their menstrual cycles-including prereceptive (luteinizing hormone [LH] + 3 days/LH + 5 days), receptive (LH + 7 days), and post-receptive (LH + 9 days) phases-were subjected to transcriptomic analysis using messenger RNA (mRNA)-enriched RNA-Seq. Feature genes were obtained and used to train the predictor for endometrial dating, with 63 samples for the training set and 27 samples for the validation set. Differentially expressed genes (DEGs) were identified by comparing samples from different phases of the menstrual cycle. Based on the transcriptomic feature genes, we constructed a bioinformatic predictor for endometrial dating. The accuracy on assessment of the endometrium on days LH + 3, LH + 5, LH + 7, and LH + 9 was 100% in the training set and 85.19% in the validation set. CONCLUSION(S): Our transcriptomic profiling method can be used to monitor the window of implantation with regard to the endometrium in the Chinese population. This method potentially provides an evaluation of endometrial status, and can be used to predict a personal window of implantation by reproductive medicine clinicians.

Alpha-glucosidase inhibitor 1-Deoxynojirimycin promotes beige remodeling of 3T3-L1 preadipocytes via activating AMPK.

Obesity is a serious health challenge in the world, and searching effective drugs to cure obesity is of great importance. 1-Deoxynojirimycin (DNJ) is extracted from mulberry leaves and acts as an α-glucosidase inhibitor to lower blood glucose. Recent studies demonstrated that it also has anti-obesity effect, but the mechanisms remain unknown. In our present study, we mainly examined the effects of DNJ on beige remodeling of 3T3-L1 preadipocytes. We observed that DNJ didn't affect the mRNA levels of fatty acid binding protein 4 (aP2), peroxisome proliferator-activated receptor γ (PPARγ), preadipocyte factor-1 (Pref-1) as well as the mitochondrial uncoupling protein 1 (UCP1), PR domain containing protein 16 (PRDM16), transmembrane protein 26 (TMEM26) in undifferentiated preadipocytes. But after inducing 3T3-L1 preadipocytes to differentiation with white or beige adipogenic medium, DNJ significantly reduced aP2, PPARγ and Pref-1 expressions, while up-regulated the expressions of UCP1, PRDM16 and TMEM26, accompanying with decreased lipid deposition. The ratio of p-AMPK/AMPK was up-regulated by DNJ (10 µM) treatment for 10 days, and the effects of DNJ on p-AMPK/AMPK, UCP1 and PRDM16 could be blocked by AMPK inhibitor Compound C. These results demonstrated that hypoglycemic agent DNJ could suppress the adipogenesis during the differentiation of white preadipocytes, and promote the switch of white preadipocytes to beige adipocytes via activating AMPK, which provided new mechanisms for explaining the benefits of DNJ on obesity-related disorders.

Energetic and kinetic dataset on interaction of the vacancy and self-interstitial atom with the grain boundary in α-iron.

We provide the dataset of the vacancy (interstitial) formation energy, segregation energy, diffusion barrier, vacancy-interstitial annihilation barrier near the grain boundary (GB) in bcc-iron and also the corresponding interactive range. The vacancy-interstitial annihilation mechanisms in the bulk, near the GB and at the GB at across scales were given.

Synthesis of γ-monofluorinated goniothalamin analogues via regio- and stereoselective ring-opening hydrofluorination of epoxide.

A stereoselective synthesis of the biologically interesting γ-monofluorinated goniothalamin analogue 2a was described. The features of the synthesis included regioselective reduction of the unprotected hydroxypropynyl moiety of compound 10 by Red-Al, asymmetric Sharpless epoxidation of allyl alcohol 11, and regio- and stereoselective ring-opening hydrofluorination of the hydroxypropynyl epoxide 14 with Et(3)N·3HF in high ee and dr. The chiral hydroxypropynyl fluorohydrin 15 was used as a valuable building block for preparation of a range of γ-monofluorinated α,ß-unsaturated δ-lactones.