The landscape of alternative splicing in granulosa cells and a potential novel role of YAP1 in PCOS.

Polycystic ovary syndrome (PCOS) is a prevalent yet complex reproductive endocrine disorder affecting 11-13% of women worldwide. Its main symptoms include elevated androgen levels, irregular menstrual cycles, and long-term metabolic and offspring health implications. Despite the disease's multifaceted nature involving genetic, epigenetic, and environmental factors, the role of alternative splicing in ovarian granulosa cells remains relatively unexplored.

Inhibition of neddylation disturbs zygotic genome activation through histone modification change and leads to early development arrest in mouse embryos.

Post-translational modification and fine-tuned protein turnover are of great importance in mammalian early embryo development. Apart from the classic protein degradation promoting ubiquitination, new forms of ubiquitination-like modification are yet to be fully understood. Here, we demonstrate the function and potential mechanisms of one ubiquitination-like modification, neddylation, in mouse preimplantation embryo development.

Differential alternative splicing landscape identifies potentially functional RNA binding proteins in early embryonic development in mammals.

Alternative splicing (AS) as one of the important post-transcriptional regulatory mechanisms has been poorly studied during embryogenesis. In this study, we comprehensively collected and analyzed the transcriptome data of early embryos from human and mouse. We found that AS plays an important role in this process and predicted candidate RNA binding protein (RBP) regulators that are associated with reproductive development.

Activation of HAND2-FGFR signaling pathway by lncRNA HAND2-AS1 in adenomyosis†.

Heart and neural crest derivatives expressed transcript 2 (HAND2) is a critical mediator of progesterone action in endometrial stromal cells. Silencing of Hand2 expression in mouse uterus leads to an unopposed FGFR-mediated action that causes female mice infertility. To investigate the involvement of HAND2-FGFR signaling in pathogenesis of adenomyosis, immunohistochemistry, in situ hybridization, and quantitative real-time PCR were employed to assess gene expression in the normal endometrium, the paired eutopic endometrium and ectopic lesions obtained from women with adenomyosis.

Cerebral delivery of redox-responsive lenalidomide prodrug plus methotrexate for primary central nerve system lymphoma combination therapy.

Primary central nervous system lymphoma (PCNSL) is an extremely malignant CNS tumor with high incidence and mortality rates. Its chemotherapy in the clinic has been restricted owing to unsatisfactory drug distribution in the cerebral tissues. In this study, a redox-responsive prodrug of disulfide-lenalidomide-methoxy polyethylene glycol (LND-DSDA-mPEG) was successfully developed for the cerebral delivery of lenalidomide (LND), and methotrexate (MTX) via subcutaneous (s.

Regulation of HAND2 Expression by LncRNA in Ovarian Endometriosis Involving DNA Methylation.

HAND2 is a critical mediator of progesterone receptor signaling in endometrium. Silencing of expression is associated with female infertility and endometrial cancers. We recently observed that lncRNA and are expressed coordinately in human endometrial stromal cells.

A 1-kb human CDCA8 promoter directs the spermatogonia-specific luciferase expression in adult testis.

Cell division cycle associated 8 (CDCA8) is a component of the chromosomal passenger complex and plays an essential role in mitosis, meiosis, cancer growth, and undifferentiated state of embryonic stem cells. However, its expression and role in adult tissues remain largely uncharacterized. Here, we studied the CDCA8 transcription in adult tissues by generating a transgenic mouse model, in which the luciferase was driven by a 1-kb human CDCA8 promoter.

Neddylation Inhibition Causes Impaired Mouse Embryo Quality and Blastocyst Hatching Failure Through Elevated Oxidative Stress and Reduced IL-1β.

Mammalian blastocyst hatching is an essential prerequisite for successful embryo implantation. As the rate-limiting step of current assisted reproductive technology, understanding the key factors regulating blastocyst hatching would be significantly helpful to improve the performance of the assisted reproductive practice. In early embryo development, the fine-tuned elimination of maternal materials and the balanced protein turnover are inevitable for the competent to hatch and implant into endometrium.

The Influence of Heavy Metals on Gastric Tumorigenesis.

Objectives: This study aimed to observe the relationship among heavy metals concentration, microsatellite instability (MSI), and human epidermal growth factor receptor type 2 (HER2) gene amplification in gastric cancer (GC) patients.

Methods: The concentrations of 18 heavy metals in the plasma of GC patients and healthy controls were measured by inductive coupled plasma emission spectrometry (ICP-MS). MSI detection was conducted by detecting 5 microsatellite repeat markers by PCR analysis.

Target-Sequencing of Female Infertility Pathogenic Gene Panel and a Novel TUBB8 Loss-of-Function Mutation.

Genetic screening is an important approach for etiology determination and helps to optimize administration protocols in reproductive centers. After the first pathogenic gene of female infertility was reported in 2016, more and more new pathogenic genes were discovered, and we sought to develop an efficient and cost-effective method for genetic screening in patients. In this study, we designed a target-sequencing panel with 22 female infertility-related genes, namely, TUBB8, PATL2, WEE2, and PANX1 and sequenced 68 primary infertility (PI) and recurrent pregnancy loss (RPL) patients.

[Impact of the expression of DNA methyltransferase 1 on the differentiation of spermatogonial stem cells in mice].

Objective: To investigate the influence of the expression of DNA methyltransferase 1 (DNMT1) on the differentiation of spermatogonial stem cells (SSC) in mice.

Methods: SSCs were isolated from the testis tissue of 1-week-old BALB/c male mice by two-step enzyme digestion. DNMT1-siRNA and negative control siRNA (NC-siRNA) were transfected into the third-generation SSCs after isolation and purification, and the untransfected cells were used as the control.

Clinical Effect of Nimodipine Combined with Magnesium Sulfate on Pregnancy-Induced Hypertension Syndrome.

The incidence of pregnancy-induced hypertension in China is 9.4%, which is at a relatively high level. Its serious impact on maternal and infant health is the main reason for maternal and perinatal morbidity and mortality.

Redox-responsive self-assembled polymeric nanoprodrug for delivery of gemcitabine in B-cell lymphoma therapy.

Gemcitabine, as a standard and classic strategy for B-cell lymphoma in the clinic, is limited by its poor pharmacodynamics. Although stimuli-responsive polymeric nanodelivery systems have been widely investigated in the past decade, issues such as complicated procedures, low loading capacity, and uncontrollable release kinetics still hinder their clinical translation. In view of the above considerations, we attempt to construct hyperbranched polyprodrug micelles with considerable drug loading via simple procedures and make use of the particularity of the tumor microenvironment to ensure that the micelles are "inactivated" in normal tissues and "activated" in the tumor microenvironment.

A ratiometric fluorescent nanoprobe for signal amplification monitoring of intracellular telomerase activity.

Telomerase is considered a valuable diagnostic and prognostic cancer biomarker. Accurate and reliable detection of telomerase activity is of great value in clinical diagnosis, screening of inhibitors, and therapeutics. Here, we developed a novel amplified fluorescence resonance energy transfer (FRET) nanoprobe for highly sensitive and reliable monitoring of intracellular telomerase activity.

Effects of the Zishen Yutai Pill Compared With Placebo on Live Births Among Women in a Fresh Embryo Transfer Cycle: A Randomized Controlled Trial.

Objective: To assess the efficacy of the Zishen Yutai Pill compared with placebo on live birth rates among women after fresh embryo transfer cycles.

Methods: We conducted a double-blind, multicenter, placebo-controlled, randomized trial to investigate whether administration of the Zishen Yutai Pill would improve pregnancy outcomes among women undergoing fresh embryo transfer after in vitro fertilization or intracytoplasmic sperm injection. The primary outcome was live birth rate.

Clinical Significance of Monitoring Circulating Free DNA and Plasma Heat Shock Protein 90alpha in Patients with Esophageal Squamous Cell Carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) is the predominant histological type of esophageal cancer in China and has an extremely poor prognosis. Circulating free DNA (cfDNA) and plasma heat shock protein 90alpha (Hsp90a) are two novel noninvasive biomarkers for diagnosis and prognostic prediction of several types of cancer. However, to the best of our knowledge, the roles of the two biomarkers in ESCC are still unknown.

Downregulation of miR-200a Protects Mouse Leydig Cells Against Triptolide by Triggering Autophagy.

Background: MicroRNAs play important roles in testicular development and spermatogenesis. Previous research has indicated that the level of miR-200a was significantly upregulated in patients with different spermatogenic impairments. However, the mechanism by which miR-200a regulated spermatogenic impairments remains unclear.

Overcoming therapeutic failure in osteosarcoma Apatinib-encapsulated hydrophobic poly(ester amide) nanoparticles.

Anti-angiogenic tyrosine kinase inhibitors (TKIs) have been proved to be effective in prolonging progression-free survival in advanced osteosarcoma. However, osteosarcoma stem-like cells persist for a long time and ultimately cause disease recurrence and therapy resistance. Here, we reveal that inefficient accumulation of Apatinib, an anti-angiogenic TKI, induces the expression of ribosome-associated genes in osteosarcoma, and confers apoptosis resistance.

Hepatic HuR modulates lipid homeostasis in response to high-fat diet.

Lipid transport and ATP synthesis are critical for the progression of non-alcoholic fatty liver disease (NAFLD), but the underlying mechanisms are largely unknown. Here, we report that the RNA-binding protein HuR (ELAVL1) forms complexes with NAFLD-relevant transcripts. It associates with intron 24 of Apob pre-mRNA, with the 3'UTR of Uqcrb, and with the 5'UTR of Ndufb6 mRNA, thereby regulating the splicing of Apob mRNA and the translation of UQCRB and NDUFB6.

Overexpression of RASAL1 Indicates Poor Prognosis and Promotes Invasion of Ovarian Cancer.

RAS protein activator like-1 (RASAL1) exists in numerous human tissues and has been commonly demonstrated to act as a tumor suppressor in several cancers. This study aimed to identify the functional characteristics of RASAL1 in ovarian adenocarcinoma and a potential mechanism of action. We analyzed RASAL1 gene expression in ovarian adenocarcinoma samples and normal samples gained from the GEO and Oncomine databases respectively.

MicroRNA‑181 exerts an inhibitory role during renal fibrosis by targeting early growth response factor‑1 and attenuating the expression of profibrotic markers.

Progressive renal fibrosis is a common complication of chronic kidney disease that results in end‑stage renal disorder. It is well established that several microRNAs (miRs) function as critical regulators implicated in fibrotic diseases. However, the role of miR‑181 in the development and progression of renal fibrosis remains unclear, and the precise mechanism has not yet been fully defined.

Ovarian IL-1α and IL-1β levels are associated with primary ovarian insufficiency.

Primary ovarian insufficiency (POI) is characterized by premature ovarian failure and lack of menstrual periods in women under the age of 40. Ample evidence suggests that interleukin 1 (IL-1) family proteins are involved in the processes of ovarian follicular development and depletion. The association of these cytokines with POI disorder and the underlying molecular mechanism in regulation of the ovarian functions remain largely undetermined.

ERβ compensates for the absence of ERα function to promote osteoblast viability by inhibition of SOST signaling.

Estrogen receptors α and β (ERα and ERβ) serve key functions in bone development and maintenance, and in the metabolism of bone mineral. ERβ and ERα form heterodimers, and ERβ negatively regulates the transactivation of ERα. ERβ also inhibits recruitment of ERα to the estrogen-responsive promoters.

FOXJ2 controls meiosis during spermatogenesis in male mice.

Spermatogenesis is a highly complex cell differentiation process necessary for production of haploid spermatozoa. Central to this unique process is spermatocyte meiosis. FOXJ2 (Forkhead box J2), a FOX transcription factor, is specifically expressed in meiotic spermatocytes in adult mouse testes, so we used a germ cell specific conditional knockout model (Foxj2(flox/flox) , Mvh-Cre) to explore its role in spermatogenesis.