Network pharmacology uncovers that secoisolariciresinol diglucoside ameliorate premature ovarian insufficiency via PI3K/Akt pathway.

As one of the essential lignan derivative found in traditional Chinese medicinal herbs, secoisolariciresinol diglucoside (SDG) was proved to promote women's health through its phytoestrogenic properties. Increasingly studies indicated that this compound could be a potential drug capable of preventing estrogen-related diseases. Here, we aimed to investigate whether SDG can counteract cyclophosphamide (CTX) induced premature ovarian insufficiency (POI) and further explore its specific molecular mechanism.

Development of an integrated and project-based laboratory course in upper-level biochemistry and molecular biology.

An integrated and projected-based laboratory course was described, integrating interconnected knowledge points and biochemistry and molecular biology techniques on a research project-based system. The program, which served as an essential extension of theoretical courses to practice, was conducted with a sophomore of basic medical science who had completed the course in medical biochemistry and molecular biology. This course engaged students in learning "genetic manipulation" and "recombinant DNA technology" to understand the target gene's role in disease mechanics, thus altering evaluation and treatment for clinical disease.

Metformin protects ovarian granulosa cells in chemotherapy-induced premature ovarian failure mice through AMPK/PPAR-γ/SIRT1 pathway.

Premature ovarian failure (POF) caused by chemotherapy is a growing concern for female reproductive health. The use of metformin (MET), which has anti-oxidative and anti-inflammatory effects, in the treatment of POF damaged by chemotherapy drugs remains unclear. In this study, we investigated the impact of MET on POF caused by cyclophosphamide (CTX) combined with busulfan (BUS) and M1 macrophages using POF model mice and primary granule cells (GCs).

Inhibition of PRKAA/AMPK (Ser485/491) phosphorylation by crizotinib induces cardiotoxicity via perturbing autophagosome-lysosome fusion.

Crizotinib, a small-molecule tyrosine kinase inhibitor targeting ALK, MET and ROS1, is the first-line drug for ALK-positive metastatic non-small cell lung cancer and is associated with severe, sometimes fatal, cases of cardiac failure, which increases the risk of mortality. However, the underlying mechanism remains unclear, which causes the lack of therapeutic strategy. We established in vitro and in vivo models for crizotinib-induced cardiotoxicity and found that crizotinib caused left ventricular dysfunction, myocardial injury and pathological remodeling in mice and induced cardiomyocyte apoptosis and mitochondrial injury.

ceRNA networks in gynecological cancers progression and resistance.

Gynecological cancers are the second most common types of cancer in women. Clinical diagnosis of these cancers is often delayed or misdiagnosed due to lack of insight into their tumorigenesis mechanism and specific diagnostic biomarkers. Many studies have demonstrated that competing endogenous RNAs (ceRNAs) modulate the progression and resistance of gynecological cancer through microRNA (miRNA)-mediated mechanisms, which affect gene expression in multiple cancer-related pathways.

Mechanisms of and Potential Medications for Oxidative Stress in Ovarian Granulosa Cells: A Review.

Granulosa cells are essential for follicle initiation and development, and their abnormal function or apoptosis is a crucial factor leading to follicular atresia. A state of oxidative stress occurs when the balance between the production of reactive oxygen species and the regulation of the antioxidant system is disturbed. Oxidative stress is one of the most important causes of the abnormal function and apoptosis of granulosa cells.

Crizotinib induces pulmonary toxicity by blocking autophagy flux in alveolar epithelial cells.

Crizotinib is the first-line drug for advanced non-small cell lung cancer with the abnormal expression of anaplastic lymphoma kinase gene. Severe, life-threatening, or fatal interstitial lung disease/pneumonia has been reported in patients treated with crizotinib. The clinical benefit of crizotinib is limited by its pulmonary toxicity, but the underlying mechanisms have not been adequately studied, and protective strategies are relatively scarce.

Evaluating the impact of radiofrequency spectroscopy on reducing reoperations after breast conserving surgery: A meta-analysis.

Background: The benefits of breast conserving surgery for breast cancer patients are well established. To achieve adequate margins of excision, intraoperative management of breast margins is a critical factor through reducing reoperation for inadequate positive margin excision and associated morbidity and cost. Radiofrequency spectroscopy is a technology that could significantly reduce positive margins when used intraoperatively as an adjunct to other margin management methods.

PTX3 from vascular endothelial cells contributes to trastuzumab-induced cardiac complications.

Aims: Trastuzumab, the first humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (ERBB2/HER2), is currently used as a first-line treatment for HER2 (+) tumours. However, trastuzumab increases the risk of cardiac complications without affecting myocardial structure, suggesting a distinct mechanism of cardiotoxicity.

Methods And Results: We used medium from trastuzumab-treated human umbilical vein endothelial cells (HUVECs) to treat CCC-HEH-2 cells, the human embryonic cardiac tissue-derived cell lines, and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to assess the crosstalk between vascular endothelial cells (VECs) and cardiomyocytes.

Role of ceRNAs in non-tumor female reproductive diseases†.

The molecular mechanism of non-tumor female reproductive diseases is complicated and needs to be further elucidated. Recently, increasing evidence indicates that non-coding RNAs(ncRNAs) which are extremely rich in the female reproductive system are crucial factors in the pathogenesis of some female reproductive disorders. In fact, these ncRNAs such as lncRNAs, circRNAs, snoRNAs, and pseudogenes that share the same miRNA response elements (MREs) with mRNAs could compete for miRNA binding site to regulate gene expression, this phenomenon is known as the competing endogenous RNAs(ceRNAs) mechanism.

UFL1 alleviates ER stress and apoptosis stimulated by LPS via blocking the ferroptosis pathway in human granulosa-like cells.

Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) is a unique E3 ligase of the UFMylation system. Recent studies have shown that this enzyme plays a crucial role in the processes of endoplasmic reticulum stress (ER stress) and apoptosis. Lipopolysaccharide (LPS) can cause injury to ovarian granule cells and hinder follicular development by triggering ER stress and apoptosis.

Ubiquitin-like modifier 1 ligating enzyme 1 relieves cisplatin-induced premature ovarian failure by reducing endoplasmic reticulum stress in granulosa cells.

Background: Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1), the ligase of the UFMylation system, has recently been reported to be involved in apoptosis and endoplasmic reticulum stress (ER stress) in a variety of diseases. Premature ovarian failure (POF) is a gynecological disease that severely reduces the fertility of women, especially in female cancer patients receiving chemotherapy drugs. Whether UFL1 is involved in protection against chemotherapy-induced POF and its mechanism remain unclear.

Application of artificial intelligence in the diagnosis and prognostic prediction of ovarian cancer.

In recent years, the wide application of artificial intelligence (AI) has dramatically improved the work efficiency of clinicians and reduced their workload. This review provides a glance at the latest advances in AI-assisted diagnosis and prognostic prediction of ovarian cancer (OC). We performed an advanced search in PubMed and IEEE/IET Electronic Library, and included 39 articles in this review.

Bisdemethoxycurcumin alleviates vandetanib-induced cutaneous toxicity in vivo and in vitro through autophagy activation.

High incidence of cutaneous toxicity ranging from 29.2% to 71.2% has been reported during clinical use of vandetanib, which is a multi-target kinase inhibitor indicated for the treatment of unresectable medullary thyroid carcinoma.

Hydrogen-rich saline mitigates pressure overload-induced cardiac hypertrophy and atrial fibrillation in rats via the JAK-STAT signalling pathway.

Objective: To investigate if hydrogen-rich saline (HRS), which has been shown to have antioxidant and anti-inflammatory properties, could mitigate cardiac remodelling and reduce the incidence of atrial fibrillation (AF) in the rat model of cardiac hypertrophy.

Methods: Pressure overload was induced in rats by abdominal aortic constriction (AAC). The animals were separated into four groups: sham; AAC group; AAC plus low dose HRS (LHRS); AAC plus high dose HRS (HHRS).

Essential Role of Ubiquitin-Fold Modifier 1 Conjugation in DNA Damage Response.

Both endogenous and exogenous factors can cause DNA damage that compromises genomic integrity and cell viability. A proper DNA damage response (DDR) plays a role in maintaining genome stability and preventing tumorigenesis. DNA double-strand breaks (DSBs) are the most toxic DNA lesion, whose response is dominated by the ataxia-telangiectasia mutated (ATM) protein kinase.

Resveratrol Plays a Protective Role against Premature Ovarian Failure and Prompts Female Germline Stem Cell Survival.

This study was designed to investigate the protective effect of resveratrol (RES) on premature ovarian failure (POF) and the proliferation of female germline stem cells (FGSCs) at the tissue and cell levels. POF mice were lavaged with RES, and POF ovaries were co-cultured with RES and/or GANT61 in vitro. FGSCs were pretreated with Busulfan and RES and/or GANT61 and co-cultured with M1 macrophages, which were pretreated with RES.

Hedgehog pathway inhibition causes primary follicle atresia and decreases female germline stem cell proliferation capacity or stemness.

Background: Follicle depletion is one of the causes of premature ovarian failure (POF) and primary ovarian insufficiency (POI). Hence, maintenance of a certain number of female germline stem cells (FGSCs) is optimal to produce oocytes and replenish the primordial follicle pool. The mechanism that regulates proliferation or stemness of FGSCs could contribute to restoring ovarian function, but it remains uncharacterized in postnatal mammalian ovaries.

Ufl1/RCAD, a Ufm1 E3 ligase, has an intricate connection with ER stress.

Ufmylation is a type of post-translational modification that deals with complex and fine-tuned cellular activities. This modification proceeds mainly through a three-step enzymatic reaction with ubiquitin-fold modifier 1 (Ufm1), ubiquitin-like modifier-activating enzyme 5 (Uba5), Ufm1-conjugating enzyme 1 (Ufc1) and Ufm1-specific ligase 1 (Ufl1). Ufl1 has previously been reported to function as a Ufm1 E3 ligase in the ufmylation system, but knowledge of its physiological functions remains poor.

Indispensable role of the Ubiquitin-fold modifier 1-specific E3 ligase in maintaining intestinal homeostasis and controlling gut inflammation.

Intestinal exocrine secretory cells, including Paneth and goblet cells, have a pivotal role in intestinal barrier function and mucosal immunity. Dysfunction of these cells may lead to the pathogenesis of human diseases such as inflammatory bowel disease (IBD). Therefore, identification and elucidation of key molecular mechanisms that regulate the development and function of these exocrine cells would be crucial for understanding of disease pathogenesis and discovery of new therapeutic targets.

Role of the Hedgehog Signaling Pathway in Regulating the Behavior of Germline Stem Cells.

Germline stem cells (GSCs) are adult stem cells that are responsible for the production of gametes and include spermatogonial stem cells (SSCs) and ovarian germline stem cells (OGSCs). GSCs are located in a specialized microenvironment in the gonads called the niche. Many recent studies have demonstrated that multiple signals in the niche jointly regulate the proliferation and differentiation of GSCs, which is of significance for reproductive function.

The Hippo Signaling Pathway Regulates Ovarian Function via the Proliferation of Ovarian Germline Stem Cells.

Objective: To improve the separation, identification and cultivation of ovarian germline stem cells (OGSCs), to clarify the relationship between the Hippo signaling pathway effector YAP1 and the proliferation and differentiation of OGSCs in vitro and to identify the major contribution of Hippo signaling to ovarian function.

Methods: Two-step enzymatic separation processes and magnetic separation were used to isolate and identify OGSCs by determining the expression of Mvh, Oct4, Nanog, Fragilis and Stella markers. Then, YAP1, as the main effector molecule in the Hippo signaling pathway, was chosen as the target gene of the study.

The effect of the immune system on ovarian function and features of ovarian germline stem cells.

In addition to its role in maintaining organism homeostasis, the immune system also plays a crucial role in the modulation of ovarian function, as it regulates ovarian development, follicular maturation, ovulation and the formation of the corpus luteum. Ovarian germline stem cells are pluripotent stem cells derived from the ovarian cortex that can differentiate into ovarian germ cells and primary granulosa cells. Recent work has demonstrated that the proliferation and differentiation of ovarian germline stem cells is regulated in part by immune cells and their secreted factors.

TDO as a therapeutic target in brain diseases.

Tryptophan-2, 3-dioxygenase (TDO) is a heme-containing protein catalyzing the first reaction in the kynurenine pathway, which incorporates oxygen into the indole moiety of tryptophan and catalyzes it into kynurenine (KYN). The activation of TDO results in the depletion of tryptophan and the accumulation of kynurenine and its metabolites. These metabolites can affect the function of neurons and inhibit the proliferation of T cells.

The Controversy, Challenges, and Potential Benefits of Putative Female Germline Stem Cells Research in Mammals.

The conventional view is that female mammals lose their ability to generate new germ cells after birth. However, in recent years, researchers have successfully isolated and cultured a type of germ cell from postnatal ovaries in a variety of mammalian species that have the abilities of self-proliferation and differentiation into oocytes, and this finding indicates that putative germline stem cells maybe exist in the postnatal mammalian ovaries. Herein, we review the research history and discovery of putative female germline stem cells, the concept that putative germline stem cells exist in the postnatal mammalian ovary, and the research progress, challenge, and application of putative germline stem cells in recent years.