Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for new-onset gastric cancer and gastric diseases in patients with type 2 diabetes mellitus: a population-based cohort study.

Objective: To compare the risks of gastric cancer and other gastric diseases in patients with type-2 diabetes mellitus (T2DM) exposed to sodium-glucose cotransporter 2 inhibitors (SGLT2I), dipeptidyl peptidase-4 inhibitors (DPP4I) or glucagon-like peptide-1 receptor agonists (GLP1a).

Design: This was a population-based cohort study of prospectively collected data on patients with T2DM prescribed SGLT2I, DPP4I or GLP1a between January 1st 2015 and December 31st 2020 from Hong Kong. The outcomes were new-onset gastric cancer, peptic ulcer (PU), acute gastritis, non-acute gastritis, and gastroesophageal reflux disease (GERD).

MicroRNA-135a-induced formation of CD133+ subpopulation with cancer stem cell properties in cervical cancer.

Cancer stem cells (CSCs) play significant roles in tumor initiation. MicroRNA-135a (miR-135a) induced the formation of a CD133+ subpopulation from a human papillomavirus-immortalized cervical epithelial cell line. Compared with the CD133- cells, the CD133+ cells expressed higher levels of miR-135a and OCT4, exhibited significantly higher tumorsphere forming capacity and the time required for tumorsphere formation was shortened in the second generation.

Myometrial Cells Stimulate Self-Renewal of Endometrial Mesenchymal Stem-Like Cells Through WNT5A/β-Catenin Signaling.

Human endometrium undergoes cycles of proliferation and differentiation throughout the reproductive years of women. The endometrial stem/progenitor cells contribute to this regenerative process. They lie in the basalis layer of the endometrium next to the myometrium.

Polymer-based precipitation preserves biological activities of extracellular vesicles from an endometrial cell line.

Extracellular vesicles (EVs) are membrane-bound vesicles released by cells and act as media for transfer of proteins, small RNAs and mRNAs to distant sites. They can be isolated by different methods. However, the biological activities of the purified EVs have seldom been studied.

A meta-analysis of the impact of human leukocyte antigen-G on the outcomes of IVF/ICSI.

This analysis was performed to determine whether the presence of soluble human leukocyte antigen-G (sHLA-G) in embryo culture medium is predictive of clinical outcomes in IVF treatment. The outcomes of implantation, clinical pregnancy, multiple pregnancy and miscarriage, between groups with and without sHLA-G in embryo culture media, were analysed. Fifteen studies with a total of 6170 cases were included.

MicroRNA and Embryo Implantation.

Problem: In mammals, implantation involves interactions between an activated blastocyst and a receptive endometrium. There are controversies on the role of microRNAs in preimplantation embryo development. The actions of endometrial microRNAs on implantation are beginning to be understood.

Annexin A2 Acts as an Adhesion Molecule on the Endometrial Epithelium during Implantation in Mice.

To determine the function of Annexin A2 (Axna2) in mouse embryo implantation in vivo, experimental manipulation of Axna2 activities was performed in mouse endometrial tissue in vivo and in vitro. Histological examination of endometrial tissues was performed throughout the reproduction cycle and after steroid treatment. Embryo implantation was determined after blockage of the Axna2 activities by siRNA or anti-Axna2 antibody.

Two-dimensional liquid chromatography with tandem mass spectrometry-based proteomic characterization of endometrial luminal epithelial surface proteins responsible for embryo implantation.

Objective: To identify endometrial epithelial cell surface proteins essential for blastocysts implantation.

Design: Isolation of cell-surface labeled prereceptive (pregnancy day 1) and receptive (pregnancy day 4) mouse endometrial proteins coupled to two-dimensional liquid chromatography with tandem mass spectrometry.

Setting: University research laboratory.

miR-135a leads to cervical cancer cell transformation through regulation of β-catenin via a SIAH1-dependent ubiquitin proteosomal pathway.

Human papillomaviruses (HPVs) is the principal etiological agent of cervical cancer (CC). However, exposure to the high-risk type HPV alone is insufficient for tumor formation, and additional factors are required for the HPV-infected cells to become tumorigenic. Dysregulated microRNAs (miRNAs) expression is frequently observed in cancer but their roles in the formation of CC have not been fully revealed.

MicroRNA Let-7a and dicer are important in the activation and implantation of delayed implanting mouse embryos.

Study Question: Does Let-7a have a functional role in modulating dicer expression to activate dormant mouse blastocysts for implantation?

Summary Answer: Let-7a post-transcriptionally regulates dicer expression altering microRNA expression to affect the implantation competency of the activated blastocysts.

What Is Known Already: The Let-7a microRNA is up-regulated during blastocyst dormancy and its forced-expression suppresses embryo implantation in vitro and in vivo. Dicer is a Let-7 target, which processes pre-microRNA to mature microRNA.

Identification of CD147 (basigin) as a mediator of trophoblast functions.

Study Question: Does CD147 regulate trophoblast functions in vitro?

Summary Answer: CD147 exists as a receptor complex on human trophoblast and regulates the implantation, invasion and differentiation of trophoblast.

What Is Known Already: CD147 is a membrane protein implicated in a variety of physiological and pathological conditions due to its regulation of cell-cell recognition, cell differentiation and tissue remodeling. Reduced placental CD147 expression is associated with pre-eclampsia, but the mechanism of actions remains unclear.

Development and characterization of an endometrial tissue culture model for study of early implantation events.

Objective: To improve and characterize an endometrial tissue culture model.

Design: Experimental study of the characteristics of mouse endometrial tissue cultured on amniotic membrane matrix.

Setting: University research laboratory.

Study of transforming growth factor alpha for the maintenance of human embryonic stem cells.

Human embryonic stem cells (hESCs) have great potential for regenerative medicine as they have self-regenerative and pluripotent properties. Feeder cells or their conditioned medium are required for the maintenance of hESC in the undifferentiated state. Feeder cells have been postulated to produce growth factors and extracellular molecules for maintaining hESC in culture.

Proteomic analysis reveals platelet factor 4 and beta-thromboglobulin as prognostic markers in severe acute respiratory syndrome.

Previously, we reported that proteomic fingerprints were present in sera of patients with severe acute respiratory syndrome (SARS), and could separate patients into subgroups with different prognoses. In the present study, we examined the prognostic values of the SARS-associated proteomic features by biostatistical analysis, and deciphered the identities of those with prognostic values. Data of 20 SARS-associated serum proteomic features and ten serological variables from 38 SARS adult patients before treatment were subjected to multivariate logistic regression.

Involvement of microRNA lethal-7a in the regulation of embryo implantation in mice.

MicroRNAs interact with multiple mRNAs resulting in their degradation and/or translational repression. This report used the delayed implantation model to determine the role of miRNAs in blastocysts. Dormant blastocysts in delayed implanting mice were activated by estradiol.

Sperm-borne microRNA-34c is required for the first cleavage division in mouse.

In mammals, the sperm deliver mRNA of unknown function into the oocytes during fertilization. The role of sperm microRNAs (miRNAs) in preimplantation development is unknown. miRNA profiling identified six miRNAs expressed in the sperm and the zygotes but not in the oocytes or preimplantation embryos.

miR-135A regulates preimplantation embryo development through down-regulation of E3 Ubiquitin Ligase Seven In Absentia Homolog 1A (SIAH1A) expression.

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules capable of regulating transcription and translation. Previously, a cluster of miRNAs that are specifically expressed in mouse zygotes but not in oocytes or other preimplantation stages embryos are identified by multiplex real-time polymerase chain reaction-based miRNA profiling. The functional role of one of these zygote-specific miRNAs, miR-135a, in preimplantation embryo development was investigated.

Wnt activation downregulates olfactomedin-1 in Fallopian tubal epithelial cells: a microenvironment predisposed to tubal ectopic pregnancy.

Ectopic pregnancy (EP) occurs when the embryo fails to transit to the uterus and attach to the luminal epithelium of the Fallopian tube (FT). Tubal EP is a common gynecological emergency and more than 95% of EP occurs in the ampullary region of the FT. In humans, Wnt activation and downregulation of olfactomedin-1 (Olfm-1) occur in the receptive endometrium and coincided with embryo implantation in vivo.

Glycodelin-A protein interacts with Siglec-6 protein to suppress trophoblast invasiveness by down-regulating extracellular signal-regulated kinase (ERK)/c-Jun signaling pathway.

During placentation, the cytotrophoblast differentiates into the villous cytotrophoblast and the extravillous cytotrophoblast. The latter invades the decidualized endometrium. Glycodelin-A (GdA) is abundantly synthesized by the decidua but not the trophoblast.

Glycodelin-A as a paracrine regulator in early pregnancy.

Glycodelin-A (GdA) is a glycoprotein secreted from the endometrial glands and decidual glandular epithelium. Given its abundance and ubiquitous distribution in the first trimester uterus, GdA may be involved in early placental development via its modulatory effect on immune and trophoblast cells. GdA inhibits activation and proliferation, and induces apoptosis of T cells.

MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of other genes by transcriptional inhibition or translational repression. miR-34a is a known tumor suppressor gene and inhibits abnormal cell growth. However, its role in other tumorigenic processes is not fully known.

Cumulus-associated alpha2-macroglobulin derivative retains proconceptive glycodelin-C in the human cumulus matrix.

Background: Glycodelin-C is a glycodelin isoform isolated from the cumulus matrix. It stimulates spermatozoa-zona pellucida binding. Here, we report the isolation and characterization of a novel glycodelin interacting protein (GIP) from human cumulus matrix.

Effects of native human zona pellucida glycoproteins 3 and 4 on acrosome reaction and zona pellucida binding of human spermatozoa.

Acrosome reaction is crucial to the penetration of spermatozoa through the zona pellucida (ZP). Glycosylation of ZP glycoproteins is important in spermatozoa-ZP interaction. Human ZP glycoprotein-3 (ZP3) is believed to initiate acrosome reaction.

Characterization of an acrosome protein VAD1.2/AEP2 which is differentially expressed in spermatogenesis.

The release of enzymes from the acrosome of the sperm head (acrosome reaction) starts the fertilization process and enables the spermatozoa to penetrate the zona pellucida of the oocytes. Defective acrosome reaction is one of the important causes of infertility in men. To investigate the molecular regulation of spermatogenesis in vivo, we used differential display reverse transcription-polymerase chain reaction to identify stage-specific genes in a retinol-supplemented vitamin-A deficiency (VAD) rat model and identified the VAD1.

Native human zona pellucida glycoproteins: purification and binding properties.

Background: Fertilization starts with the binding of the spermatozoa to the zona pellucida (ZP) of the oocyte. Such binding is a carbohydrate-mediated event and consists of a series of tightly regulated events. Molecular interactions between spermatozoon and ZP in human are not well characterized due to limited availability of oocytes for research.