Independent organelle and organelle-organelle interactions: essential mechanisms for malignant gynecological cancer cell survival.

Different eukaryotic cell organelles (e.g., mitochondria, endoplasmic reticulum, lysosome) are involved in various cancer processes, by dominating specific cellular activities. Organelles cooperate, such as through contact points, in complex biological activities that help the cell regulate energy metabolism, signal transduction, and membrane dynamics, which influence survival process. Herein, we review the current studies of mechanisms by which mitochondria, endoplasmic reticulum, and lysosome are related to the three major malignant gynecological cancers, and their possible therapeutic interventions and drug targets. We also discuss the similarities and differences of independent organelle and organelle-organelle interactions, and their applications to the respective gynecological cancers; mitochondrial dynamics and energy metabolism, endoplasmic reticulum dysfunction, lysosomal regulation and autophagy, organelle interactions, and organelle regulatory mechanisms of cell death play crucial roles in cancer tumorigenesis, progression, and response to therapy. Finally, we discuss the value of organelle research, its current problems, and its future directions.

Exploring the causal role of multiple metabolites on ovarian cancer: a two sample Mendelian randomization study.

BACKGROUND: The mechanisms and risk factors underlying ovarian cancer (OC) remain under investigation, making the identification of new prognostic biomarkers and improved predictive factors critically important. Recently, circulating metabolites have shown potential in predicting survival outcomes and may be associated with the pathogenesis of OC. However, research into their genetic determinants is limited, and there are some inadequacies in understanding the distinct subtypes of OC. In this context, we conducted a Mendelian randomization study aiming to provide evidence for the relationship between genetically determined metabolites (GDMs) and the risk of OC and its subtypes. METHODS: In this study, we consolidated genetic statistical data of GDMs with OC and its subtypes through a genome-wide association study (GWAS) and conducted a two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method served as the primary approach, with MR-Egger and weighted median methods employed for cross-validation to determine whether a causal relationship exists between the metabolites and OC risk. Moreover, a range of sensitivity analyses were conducted to validate the robustness of the results. MR-Egger intercept, and Cochran's Q statistical analysis were used to evaluate possible heterogeneity and pleiotropy. False discovery rate (FDR) correction was applied to validate the findings. We also conducted a reverse MR analysis to validate whether the observed blood metabolite levels were influenced by OC risk. Additionally, metabolic pathway analysis was carried out using the MetaboAnalyst 5.0 software. RESULTS: In MR analysis, we discovered 18 suggestive causal associations involving 14 known metabolites, 8 metabolites as potential risk factors, and 6 as potential cancer risk reducers. In addition, three significant pathways, "caffeine metabolism," "arginine biosynthesis," and "citrate cycle (TCA cycle)" were associated with the development of mucinous ovarian cancer (MOC). The pathways "caffeine metabolism" and "alpha-linolenic acid metabolism" were associated with the onset of endometrioid ovarian cancer (OCED). CONCLUSIONS: Our MR analysis revealed both protective and risk-associated metabolites, providing insights into the potential causal relationships between GDMs and the metabolic pathways related to OC and its subtypes. The metabolites that drive OC could be potential candidates for biomarkers.

Mechanism of cryptotanshinone to improve endocrine and metabolic functions in the endometrium of PCOS rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cryptotanshinone is the main bioactive component of Salvia miltiorrhiza, with various mechanisms of action, including antioxidant, anti-inflammatory, cardiovascular protection, neuroprotection, and hepatoprotection. Salvia miltiorrhiza is used clinically by gynecologists in China. AIM OF THE STUDY: Polycystic ovary syndrome (PCOS) has a significant impact on women's quality of life, leading to infertility and reproductive disorders. Hence, this study aims to assess the pharmacological activity of cryptotanshinone in the treatment of PCOS and investigate its therapeutic mechanism. MATERIALS AND METHODS: Human chorionic gonadotropin (HCG) combined with insulin is used to simulate a PCOS-like rat model and attempt to discover the abnormal changes that occur and the means by which the pathway acts in this model. RESULTS: The transcriptome sequencing method is used to identify 292 differential genes that undergo significant changes, of which 219 were upregulated and 73 were downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the signaling pathways reveals that differential expressed genes are significantly enriched in 23 typical pathways. Estrogen signaling pathways are screened in the cryptotanshinone and model groups, and significant differential changes in Fos, ALOX12, and AQP8 are found. This suggests that these signaling pathways and molecules may be the main signaling targets for regulating the differences in endometrial tissue. CONCLUSION: These results indicate that cryptotanshinone has targets for regulating the proliferation of endometrial tissue via estrogen signaling pathways in PCOS-like rats, providing an experimental basis for the clinical application of cryptotanshinone in the treatment of PCOS.

Research progress on the mechanism of glycolysis in ovarian cancer.

Glycolysis is the preferred energy metabolism pathway in cancer cells even when the oxygen content is sufficient. Through glycolysis, cancer cells convert glucose into pyruvic acid and then lactate to rapidly produce energy and promote cancer progression. Changes in glycolysis activity play a crucial role in the biosynthesis and energy requirements of cancer cells needed to maintain growth and metastasis. This review focuses on ovarian cancer and the significance of key rate-limiting enzymes (hexokinase, phosphofructokinase, and pyruvate kinase, related signaling pathways (PI3K-AKT, Wnt, MAPK, AMPK), transcription regulators (HIF-1a), and non-coding RNA in the glycolytic pathway. Understanding the relationship between glycolysis and these different mechanisms may provide new opportunities for the future treatment of ovarian cancer.

Icariin as a potential anticancer agent: a review of its biological effects on various cancers.

Numerous chemical compounds used in cancer treatment have been isolated from natural herbs to address the ever-increasing cancer incidence worldwide. Therein is icariin, which has been extensively studied for its therapeutic potential due to its anti-inflammatory, antioxidant, antidepressant, and aphrodisiac properties. However, there is a lack of comprehensive and detailed review of studies on icariin in cancer treatment. Given this, this study reviews and examines the relevant literature on the chemopreventive and therapeutic potentials of icariin in cancer treatment and describes its mechanism of action. The review shows that icariin has the property of inhibiting cancer progression and reversing drug resistance. Therefore, icariin may be a valuable potential agent for the prevention and treatment of various cancers due to its natural origin, safety, and low cost compared to conventional anticancer drugs, while further research on this natural agent is needed.

[Advances in mechanism of traditional Chinese medicine in inhibiting angiogenesis in ovarian cancer].

Ovarian cancer is one of the three major cancers in gynecology. Ovarian cancer has insidious symptoms in its early stages and mostly has progressed to advanced stages when detected. Surgical treatment combined with chemotherapy is currently the main treatment, but the 5-year survival rate is still less than 45%. Angiogenesis is a key step in the growth and metastasis of ovarian cancer. The inhibition of ovarian cancer angiogenesis has become a new hotspot in anti-tumor targeted therapy, which has many advantages such as less drug resistance, high specificity, few side effects, and broad anti-tumor spectrum. Modern research has confirmed that traditional Chinese medicine(TCM) can inhibit tumor angiogenesis by inhibiting the expression of pro-angiogenic factors, up-regulating the expression of anti-angiogenic factors, inhibiting the proliferation of vascular endothelial cells, reducing the density of tumor microvessels, and regulating related signaling pathways, with unique advantages in the treatment of ovarian cancer. This paper presented a review of the role of TCM in inhibiting ovarian cancer angiogenesis in order to provide references for the optimization of clinical ovarian cancer treatment strategies.

Current Research on Complementary and Alternative Medicine in the Treatment of Premature Ovarian Failure: An Update Review.

Complementary and alternative medicine (CAM) encompasses a wide range of different non-mainstream therapies that have been increasingly used for the treatment or adjunct treatment of various ailments, with premature ovarian failure (POF) being one of the most common conditions treated with CAM. This review updates the progress of CAM in the treatment of POF, and we focus specifically on reviewing the evidence for the efficacy and mechanisms of a range of CAM treatments in POF, including single herbal medicines and their active ingredients, compound Chinese medicines, acupuncture and moxibustion, psychotherapy, exercise, vitamins, massage, and dietary supplements. According to the literature, CAM is very helpful for improving POF symptoms, and we hope to provide some instructive suggestions for clinical treatment and experimental research in the future. However, more clinical trials are needed to prove the safety of CAM.

The role of vaginal microecology in the cervical cancer.

AIM: To explore the role of vaginal microecology in cervical cancer, so as to increase the understanding of cervical cancer and lay a foundation for future large-sample clinical trials. METHODS: We reviewed and summarized the literature comprehensively, and discussed the relationship between vaginal microecology and HPV infection, CIN progression and cervical cancer, as well as the potential molecular mechanism and the prospects of probiotics and prebiotics in future cancer treatments. RESULTS: With the popularization of high-throughput sequencing technology and the development of bioinformatics analysis technology, many evidences show that the increase in the diversity of the bacterial community in the vaginal microecological environment and the decrease in the number of Lactobacilli are associated with the continuous infection of HPV and the further development of CIN, cervical cancer-related. CONCLUSIONS: Vaginal microecological imbalance has an important impact on the occurrence and development of cervical cancer. However, the pathogenesis is not completely clear, and more high-level basic research and longitudinal clinical studies are needed to verify.

Complementary and Alternative Medicine for Premature Ovarian Insufficiency: A Review of Utilization and Mechanisms.

Premature ovarian insufficiency (POI) is defined as a decline in ovarian function before the age of 40 and is one of the leading causes of infertility in women. The etiology is complex, and the pathogenesis is not clear. The main treatment is hormone replacement therapy, but a growing body of data confirms that such treatment can increase the risk of endometrial disease and cardiovascular disease. Complementary and alternative medicine (CAM) has been widely used in patients with POI due to its limited adverse reactions and high efficiency. According to literature reports, CAM therapy for POI mainly includes traditional Chinese medicine, acupuncture, psychotherapy, dietary supplements, and exercise therapy. This article reviews the application of CAM in the treatment of POI and attempts to determine the therapeutic effects and the mechanisms behind these effects based on existing clinical and experimental studies in order to provide theoretical support for the treatment of POI.

Plant-Derived Chinese Medicine Monomers on Ovarian Cancer via the Wnt/ß-Catenin Signaling Pathway: Review of Mechanisms and Prospects.

Ovarian cancer (OC) is a common malignant tumor of the female reproductive system and has a high morbidity and mortality rate. The progression and metastasis of OC are complex and involve multiple signaling pathways. The Wnt/ß-catenin signaling pathway is closely related to OC, and therefore blocking the activation of the Wnt/ß-catenin signaling directly or inhibiting related genes, and molecular targets is of great value in treating OC. Toxicities such as myelotoxicity, cardiotoxicity, genotoxicity, and vasospasm are the major side effects for common anticancer drugs and are well documented. There is, therefore, a need to develop new, effective, safer, and more affordable anticancer drugs from alternative sources. In recent years, plant-derived Chinese medicine monomers have drawn increasing attention due to their high safety, low toxicity, minimal side effects, and antitumor effects. Plant-derived Chinese medicine monomers are effective against multiple targets and can regulate the growth, proliferation, apoptosis, invasion, and migration of OC as well as reverse drug resistance by regulating the Wnt/ß-catenin signaling pathway. In this review, we summarize and provide mechanisms and prospects for the use of plant-derived Chinese medicines for the prevention and treatment of OC.

Insights into the Role of Oxidative Stress in Ovarian Cancer.

Oxidative stress (OS) arises when the body is subjected to harmful endogenous or exogenous factors that overwhelm the antioxidant system. There is increasing evidence that OS is involved in a number of diseases, including ovarian cancer (OC). OC is the most lethal gynecological malignancy, and risk factors include genetic factors, age, infertility, nulliparity, microbial infections, obesity, smoking, etc. OS can promote the proliferation, metastasis, and therapy resistance of OC, while high levels of OS have cytotoxic effects and induce apoptosis in OC cells. This review focuses on the relationship between OS and the development of OC from four aspects: genetic alterations, signaling pathways, transcription factors, and the tumor microenvironment. Furthermore, strategies to target aberrant OS in OC are summarized and discussed, with a view to providing new ideas for clinical treatment.

Complementary and Alternative Medicine for Dysmenorrhea Caused by Endometriosis: A Review of Utilization and Mechanism.

Endometriosis (EM) is a common and benign estrogen-dependent gynecological disorder among women of reproductive age, and secondary dysmenorrhea is one of the more severe symptoms. However, the mechanism behind the development of dysmenorrhea is poorly understood, and there is a lack of effective methods for diagnosing and treating EM dysmenorrhea. In this regard, complementary and alternative medicine (CAM) has recently come into widespread use due to its limited adverse reactions and high efficiency. This review updates the progress of CAM in the treatment of EM dysmenorrhea and seeks to identify the therapeutic efficacy as well as the mechanisms behind these effects based on the available clinical and experimental studies. According to the literature, CAM therapy for EM dysmenorrhea, including herbs (herbal prescriptions, extracts, and patents), acupuncture, and Chinese herbal medicine enema (CHM enema), is effective for relieving dysmenorrhea with fewer unpleasant side effects when compared to hormonal and surgical treatments. In addition, we discuss and analyze the existing gaps in the literature. We hope to provide some instructive suggestions for clinical treatment and experimental research in the future.

The Complementary and Alternative Medicine for Polycystic Ovary Syndrome: A Review of Clinical Application and Mechanism.

As a reproductive endocrine disease, polycystic ovary syndrome (PCOS) has influenced billions of women during childbearing age worldwide. Owing to its complex etiology and ambiguous pathogenesis, there is still not a specific method to cure it. Clinical treatments, such as hormone therapy and surgical treatment, have side effects. Therefore, it is essential and urgent to seek alternative treatment to solve these problems. The satisfactory efficacy of complementary and alternative medicine (CAM), such as traditional Chinese medicine (TCM), immunotherapy, medicinal foods, vitamin therapy, diet therapy, psychotherapy, spa, and oxygen therapy, in treating PCOS, has aroused an increasing number of medical workers' concern and gradually become the mainstream. This paper reviews the application of CAM in the treatment of PCOS, especially from the perspective of TCM. Meanwhile, the limitations of the literature about CAM in the treatment of PCOS are mentioned and analyzed as well.

microRNA-1271-5p/TIAM1 suppresses the progression of ovarian cancer through inactivating Notch signaling pathway.

OBJECTIVE: Ovarian cancer (OC) has been regarded as the most malignant gynecological neoplasm and often confers grave outcomes owing to the frequent metastasis and high recurrence. A previous study has demonstrated that miR-1271-5p is implicated in OC progression, however, the possible mechanism of it remains unknown. The purpose of this investigation was to explore how miR-1271-5p regulates the progression of OC. METHODS: Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were employed to analyze the differentially expressed miRNAs or genes as well as their corresponding prognostic values. miR-1271-5p expression in OC cells was examined by qRT-PCR. Cell counting kit 8 (CCK-8), colony formation, and transwell tests were conducted to evaluate the proliferation, migration and invasion potentials. Bioinformatics prediction and luciferase activity analysis were utilized to predict and verify the target gene of miR-1271-5p. Western blot assay was carried out to measure protein expression. RESULTS: miR-1271-5p was significantly decreased in OC and its down-regulation was associated with the grave outcome of OC patients. Upregulation of miR-1271-5p inhibited cell viability, but miR-1271-5p knockdown promoted the proliferation of OC cells. TIAM1 was a direct target gene of miR-1271-5p and expressed in OC tissues at higher level. High expression of TIAM1 induced the poorer prognosis of patients with OC. Further functional analyses showed that the suppressive role of miR-1271-5p on OC cell malignant behaviors was overturned by the upregulation of TIAM1. The protein levels of Cyclin D1, HES1, NOTCH and NUMB were remarkably changed due to the abnormal expression of miR-1271-5p and TIAM1. CONCLUSION: To sum up, miR-1271-5p inhibits proliferation, invasion and migration of OC cells by directly repressing TIAM1 to inactivate the Notch signaling pathway, which provides an alternative therapeutic candidate for the advancement of OC treatment.

Chinese Obstetrics & Gynecology journal club: a randomised controlled trial.

OBJECTIVES: To assess whether a journal club model could improve comprehension and written and spoken medical English in a population of Chinese medical professionals. SETTING AND PARTICIPANTS: The study population consisted of 52 medical professionals who were residents or postgraduate master or PhD students in the Department of Obstetrics and Gynecology, Heilongjiang University of Chinese Medicine, China. INTERVENTION: After a three-part baseline examination to assess medical English comprehension, participants were randomised to either (1) an intensive journal club treatment arm or (2) a self-study group. At the conclusion of the 8-week intervention participants (n=52) were re-tested with new questions. OUTCOME MEASURES: The primary outcome was the change in score on a multiple choice examination. Secondary outcomes included change in scores on written and oral examinations which were modelled on the Test of English as a Foreign Language (TOEFL). RESULTS: Both groups had improved scores on the multiple choice examination without a statistically significant difference between them (90% power). However, there was a statistically significant difference between the groups in mean improvement in scores for both written (95% CI 1.1 to 5.0; p=0.003) and spoken English (95% CI 0.06 to 3.7; p=0.04) favouring the journal club intervention. CONCLUSIONS: Interacting with colleagues and an English-speaking facilitator in a journal club improved both written and spoken medical English in Chinese medical professionals. Journal clubs may be suitable for use as a self-sustainable teaching model to improve fluency in medical English in foreign medical professionals. TRIAL REGISTRATION NUMBER: NCT01844609.

[Effect of Brucea javanica fruit oil emulsion combined cisplatin on the growth inhibition of transplanted tumor in human ovarian cancer SKOV3 nude mice: an experimental study].

OBJECTIVE: To study the growth inhibition effect of Brucea javanica Fruit Oil Emulsion (BJFOE) on human ovarian caner SKOV3 cells and the transplanted tumor of SKOV3 nude mice. METHODS: Growth inhibition effects of different concentrations BJFOE alone or its combination with cisplatin on human ovarian cancer cell SKOV3 were measured using MTT method. The orthotopic transplantation tumor model of human ovarian cancer SKOV3 cell lines was established in nude mice. Totally 32 ovarian cancer nude mice were randomly divided into 4 groups, i.e., the blank control group (Group A), the BJFOE group (Group B), the BJFOE combined Cisplatin group (Group C), and the Cisplatin control group (Group D), 8 in each group. Mice in Group A were intraperitoneally injected with normal saline (0.2 mL/ 20 g), once per two days. Mice in Group B were intraperitoneally injected with BJFOE (0.2 mL/20 g), once per two days. Mice in Group C were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL on the first day, and intraperitoneally injected with BJFOE on the second day. Mice in Group D were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL, once per two days. All mice were injected for six times, and sacrificed 48 h after the last injection. The lesion formation of the abdominal tumor tissue was observed. Tumor specimens were obtained to perform HE staining. Expression levels of MRP-1/CD9 and integrinα-5 were detected using Western blot. RESULTS: The inhibition of BJFOE was time-dose depend- ently correlated with its inhibition effect of SKOV3 cells. The inhibition effect of BJFOE in combination of cisplatin was significantly superior to that of using any of the two drugs alone. Western blot results showed expression levels of MRP-1/CD9 and integrinα-5 were up-regulated in Group B and Group D with statistical difference (P < 0.05). But they were down-regulated in Group C with statistical difference (P < 0.05). CONCLUSIONS: Intraperitoneal injecting BJFOE was feasible and effective for treating ovarian cancer. BJFOE also could inhibit the invasion and migration of tumor cells targeting at MRP-1/CD9 and integrinα-5. But its specific anti-tumor mechanism was not clearly probed.

The complementary and alternative medicine for endometriosis: a review of utilization and mechanism.

Endometriosis (EM) is one of the common gynecological conditions causing menstrual and pelvic pain and affects 10%-15% of women of reproductive age. In recent years, the complementary and alternative medical (CAM) treatment for EM has become popular due to the few adverse reactions reported. The CAM therapy for EM includes several different treatments such as herbs (herbal prescription, extract, and patent), acupuncture, microwave physiotherapy, and Chinese herb medicine enema (CHM enema). These CAM therapies are effective at relieving dysmenorrhoea, shrinking adnexal masses, and promoting pregnancy, with less unpleasant side effects when compared to hormonal and surgical treatments. In this review, we focus on the status quo of CAM on EM and try to identify therapeutic efficacy and mechanisms based on some clinical and experimental studies. We hope to provide some instructive suggestions for clinical treatment and experimental research in the future.

Clinical observation of erhuang powder's promoting the wound healing of cervical columnar epithelium ectopy after physiotherapy / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the clinical effects of Erhuang Powder (EHP) in promoting the wound healing of cervical columnar epithelium ectopy after physiotherapy.</p><p><b>METHODS</b>Sixty-four patients with moderate and severe cervical columnar epithelium ectopy accompanied with contact bleeding were assigned to the treatment group (34 cases) and the control group (30 cases) according to table of random digit. Physiotherapy of the cervix was given to all patients. EHP was externally applied to the affected site of patients in the treatment group once every 3 days. Five times consisted as one therapeutic course, totally for 2 courses. The therapeutic effects, the wound healing time, the vaginal fluid quantity, the vaginal fluid discharge time, the wound infection, and adverse reaction were observed in the two groups.</p><p><b>RESULTS</b>The healing rate of the treatment group was 85.29% (29/34), higher than that of the control group (50%, 15/30) after 8 weeks of treatment, showing statistical difference (P < 0.1). The average wound healing time of the treatment group (3.2 - 0.8 weeks) was shorter than that of the control group (5.3 +/- 0.9 weeks), showing statistical difference (P < 0.5). The vaginal fluid quantity and the vaginal fluid discharge time in the treatment group were superior to those in the control group, showing statistical difference (P < 0.5, P < 0.1). Increased vaginal secretion accompanied with foreign odor or infection occurred in 2 patients of the control group. No adverse reaction or infection occurred in the treatment group.</p><p><b>CONCLUSIONS</b>Local application of EHP could promote the wound healing of cervical columnar epithelium ectopy after physiotherapy. It could improve its healing rate. Therefore, it was one ideal and reliable method, and worthy of clinical spreading.</p>