Currently, the absence of ovarian cancer (OC)-specific biomarkers impedes the development of precise noninvasive diagnostic and monitoring strategies. Exosomal surface sialic acid (SA), a key mediator of intercellular communication and disease progression, emerges as a promising biomarker, though its role in OC remains unclear. Conventional exosome isolation and detection methods exhibit limited clinical utility. Herein, we developed a CD63 aptamer-functionalized gold array chip integrated with a surface-enhanced Raman scattering (SERS) nanosensor for sensitive SA analysis. The chip efficiently isolated exosomes from clinical serum, while the nanosensor selectively bound exosomal SA via molecular recognition, thereby altering the SERS intensity ratio of the nanosensor. More importantly, machine learning can discern SA signatures from SERS spectra, achieving 93% accuracy in OC diagnosis. The longitudinal monitoring of SA throughout the entire treatment period (preoperative, postoperative, and chemotherapy) revealed a potential correlation with treatment response as indicated by clinical markers (CA125, HE4), demonstrating the utility of exosomal SA in precision treatment evaluation. This provides a powerful tool for the diagnosis and treatment monitoring of OC and plays a critical role in precision medicine.

Epithelial ovarian carcinoma (EOC), the most lethal gynecologic cancer, is often diagnosed at advanced stages, which urge us to explore the novel therapeutic strategies. Mouse models have played a crucial role in elucidating the molecular mechanisms for the development ovarian cancer and its therapeutic strategies. However, there are still various challenges in modeling the genetic drivers of ovarian cancer in animal models. Here, we provided an overview of the research advances for the molecular mechanisms underlying EOC development, therapeutic strategies, the CRISPR genome editing technology and its generated EOC models. The review also comprehensively discussed the advantages and obstacles of CRISPR in generating EOC mouse models and the promising therapeutic approach by correcting the oncogenes of EOC through in vivo delivery of gene-edited components. The development of more precise animal models, along with a deeper understanding of EOC molecular mechanisms, will dramatically benefit the investigation and treatment of EOC.

Accumulating evidence suggests that exposure to ambient airborne PM2.5 increases the risk of primary ovarian insufficiency (POI). However, whether ferroptosis, a newly discovered type of cell death involved in PM2.5-induced lung injury and fibrosis, is involved in PM2.5-induced POI has not been determined. This study aimed to verify the involvement of PM2.5-induced ferroptosis in ovarian dysfunction and further demonstrate that melatonin inhibits ferroptosis by activating the Nrf2 signaling pathway to ameliorate POI in vivo and in vitro. In our study, PM2.5 promoted iron accumulation and induced lipid peroxidation, thus contributing to ferroptosis in KGN cells and ovaries. However, these effects were eliminated and enhanced in Nrf2-overexpressing and Nrf2-knockdown cells, respectively. In addition, melatonin and ferrostatin-1 (Fer-1) inhibited ferroptosis by activating the NRF2 signaling pathway, as evidenced by the silencing of Nrf2 in vivo and in vitro. Mechanistically, Nrf2-knockout mice were more susceptible to ferroptosis and PM2.5-induced POI than control mice. Moreover, melatonin suppressed changes in morphological and biochemical indicators related to ferroptosis, such as MDA and GSH depletion and GPX4 and XCT downregulation, by enhancing Nrf2 signaling. Here, we first reported that PM2.5 triggered ferroptosis by increasing ROS levels, lipid peroxidation and glutathione depletion. Notably, melatonin significantly decreased ferroptosis levels and improved ovarian function by activating the NRF2 signaling pathway in vivo and in vitro.

In recent years, burgeoning research has established a causal relationship between atmospheric pollution and primary ovarian insufficiency (POI). Ferroptosis, a newly discovered type of lipid reactive oxygen species- and iron-dependent cell death, contributes to POI. This study investigated how melatonin-mediated Nrf2 activation inhibits ferroptosis in PM2.5-induced ovarian dysfunction. The antiferroptotic effects of Nrf2 and melatonin were examined in PM2.5-induced KGN cells and a POI mouse model. The potential mechanisms were further investigated using PM2.5-induced Nrf2 siRNA-transfected cells in vitro and Nrf2-knockout mice in vivo. In vitro, PM2.5 promoted iron accumulation and induced lipid peroxidation, thus contributing to ferroptosis in KGN cells; however, this effect was eliminated and enhanced in Nrf2-overexpressing and Nrf2-knockdown cells, respectively. In addition, melatonin activated Nrf2 to prevent iron accumulation, lipid peroxidation and ferroptosis in PM2.5-induced KGN cells, but these effects were attenuated in Nrf2-knockdown cells. In vivo, PM2.5-induced ferroptosis and ovarian endocrine dysfunction characterized by assessments of estrus cycles, hormone levels, and ovarian reserve were alleviated by ferrostatin-1 (Fer-1) or melatonin treatment. Mechanistically, Nrf2-knockout mice were more susceptible to ferroptosis in PM2.5-induced POI than control mice. Moreover, melatonin suppressed changes in morphological and biochemical indicators related to ferroptosis, such as MDA and GSH depletion and GPX4 and xCT downregulation, by enhancing Nrf2 signaling. These effects were abolished in Nrf2-knockout mice. Nrf2-regulated ferroptosis significantly affects the ability of melatonin to alleviate PM2.5-induced POI. The findings highlight the potential ability of melatonin to prevent or slow the progression of PM2.5-induced POI.

Background: The complex formed by disulfiram (DSF) and copper (Cu) is safe and effective for the prevention and treatment of triple-negative breast cancer (TNBC). Although previous studies have shown that DSF/Cu induces ferroptosis, the mechanism remains unclear. Methods: The mitochondrial morphology of TNBC treated with DSF/Cu was observed by transmission microscopy, and intracellular levels of iron, lipid reactive oxygen species (ROS), malondialdehyde, and glutathione were evaluated to detect the presence of ferroptosis. Target genes for the DSF/Cu-activated ferroptosis signaling pathway were examined by transcriptome sequencing analysis. Expression of the target gene, HOMX1, was detected by qRT-PCR, immunofluorescence and western blot. Results: The mitochondria of TNBC cells were significantly atrophied following treatment with DSF/Cu for 24 h. Addition of DSF/Cu supplement resulted in significant up-regulation of intracellular iron, lipid ROS and malondialdehyde levels, and significant down-regulation of glutathione levels, all of which are important markers of ferroptosis. Transcriptome analysis confirmed that DSF/Cu activated the ferroptosis signaling pathway and up-regulated several ferroptosis target genes associated with redox regulation, especially heme oxygenase-1 (HMOX-1). Inhibition of ferroptosis by addition of the ROS scavenger N-acetyl-L-cysteine (NAC) significantly increased the viability of DSF/Cu-treated TNBC cells. Conclusions: These results show that DSF/Cu increases lipid peroxidation and causes a sharp increase in HMOX1 activity, thereby inducing TNBC cell death through ferroptosis. DSF/Cu is a promising therapeutic drug for TNBC and could lead to ferroptosis-mediated therapeutic strategies for human cancer.

Breast cancer has become a leading cause of cancer-related deaths in women worldwide. DNA methylation has been revealed to play an enormously important role in the development and progression of breast cancer. DNA methylation is regulated by DNA methyltransferases (DNMTs), including DNMT1, DNMT2, and DNMT3. DNMT3 family has three members: DNMT3A, DNMT3B, and DNMT3L. The roles and functions of DNMT1 in breast cancer have been well reviewed. In this article, the roles of DNMT3A and DNMT3B in breast tumorigenesis and development are reviewed. We also discuss the SNP and mutations of DNMT3A and DNMT3B in breast cancer. In addition, we summarize how DNMT3A and DNMT3B are regulated by non-coding RNAs and signaling pathways in breast cancer, and targeting the expression levels of DNMT3A and DNMT3B may be a promising therapeutic approach for breast cancer. This review will provide reference for further studies on the biological functions and molecular mechanisms of DNMT3A and DNMT3B in breast cancer.

Organic light-emitting diodes (OLEDs), which have been recently utilized in some flat-panel display screens such as mobile phones and televisions, show many merits, including light weight, high fle...

Background CXCL1 belongs to a member of the ELR + CXC chemokine subgroups that also known as GRO-alpha. It has been recognized that several types of human cancers constitutively express CXCL1, which may serve as a crucial mediator involved in cancer development and metastasis via an autocrine and/or paracrine fashion. However, the expression pattern and clinical significance of CXCL1 in human uterine cervix cancer (UCC), as well as its roles and mechanisms in UCC tumor biology remains entirely unclear. Methods The expression and clinical significance of CXCL1 in UCC tissues was explored using immunohistochemistry and bioinformatics analyses. The expression and effects of CXCL1 in HeLa UCC cells were assessed using ELISA, CCK-8 and transwell assays. Western blotting experiments were performed to evaluate the potential mechanism of CXCL1 on malignant behaviors of HeLa UCC cells. Results The current study demonstrated that CXCL1 was expressed in HeLa UCC cells, PHM1-41 human immortalized cervical stromal cells, as well as cervical tissues, with UCC tissues having an evidently high level of CXCL1. This high level of CXCL1 in cancer tissues was notably related to poor clinical stages and worse survival probability, rather than tumor infiltration and patient age. In addition, CXCL1 expression was extremely correlated with CCL20, CXCL8 and CXCL3 cancer-associated chemokines expression. In vitro, the growth and migration abilities of HeLa cells were significantly enhanced in the presence of exogenous CXCL1. Gain-function assay revealed that CXCL1 overexpression significantly promoted growth and migration response in HeLa cells in both autocrine and paracrine manners. Finally, we found that CXCL1 overexpression in HeLa cells influenced the expression of ERK signal-related genes, and HeLa cell malignant behaviors derived from CXCL1 overexpression were further interrupted in the presence of the ERK1/2 blocker. Conclusion Our findings demonstrate the potential roles of CXCL1 as a promoter and a novel understanding of the functional relationship between CXCL1 and the ERK signaling pathway in UCC.

Introduction:The comparison of ibuprofen with acetaminophen for blood pressure (BP) in preeclampsia remains controversial. We conduct a systematic review and meta-analysis to compare the impact of ibuprofenversusacetaminophen on BP for preeclampsia. Methods:We search PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases through October 2019 for randomized controlled trials (RCTs) assessing the effect of ibuprofen versus acetaminophen on BP for preeclampsia. This meta-analysis is performed using the random-effect model. Results:Four RCTs are included in the meta-analysis. Overall in preeclampsia patients, ibuprofen and acetaminophen show similar systolic BP (SBP) (standard mean difference [SMD] = 0.04; 95% CI = -0.26-0.34;p= .81), diastolic BP (DBP) (SMD = 0.15; 95% CI = -0.18-0.48;p = 0.38), mean BP (MAP) (SMD = 0.02; 95% CI = -0.29-0.33;p = .91), severe range BP (SMD = -0.10; 95% CI = -0.40-0.19;p = .50), severe hypertension (SMD = 1.18; 95% CI = 0.85-1.62;p = .32), and satisfaction level (SMD = 1.2; 95% CI = 0.95-1.53;p = .13). Conclusions:Ibuprofen and acetaminophen may have no significant influence on BP for preeclampsia.

Background Microcystic stromal tumor (MCST) of the ovary is an extremely rare subtype of sex cord-stromal neoplasm first described by Irving and Young in 2009. Tumors from all previously reported cases (fewer than 40 total) were benign, but one was a case of ovarian MCST that reoccurred. Case presentation Herein, we present a unique single case of ovarian MCST with omental metastasis in a 47-year-old Chinese female along with its histologic and immunohistochemical profile and genetic alterations. The tumor exhibited the previously described classic microscopic features and immunoprofiles of MCST. The tumorlet in the omentum presented the same histological structures and characteristically expressed β-catenin protein (localized in the nucleus). Molecular analysis identified a point mutation (c.98C > G) in exon 3 of CTNNB1 . Conclusions To the best of our knowledge, no such report has been documented for ovarian MCST with omental metastasis. The study may provide new insights into the tumor biology of MCST and provide a better understanding of this rare entity.

Background Many studies have investigated the relationship between the interleukin-1 beta gene (IL1B) -511C/T polymorphism and the risk of Behcet's disease (BD); however, the conclusions remain controversial. Methods In this study, we systemically retrieved relevant studies from the Chinese Biomedicine Database, China National Knowledge Infrastructure, Embase, Cochrane Library, and PubMed databases. We then calculated the odds ratios (ORs) and 95% confidence intervals (CIs) using the meta-package Stata version 12.0. Results The IL1B -511C/T polymorphism was not related to BD susceptibility using any of the tested models (C vs T: OR = 1.20, 95% CI = 0.97-1.49; CC vs TT: OR = 1.27, 95% CI = 0.95-1.70; CT vs TT: OR = 1.03, 95% CI = 0.781.36; dominant model: OR = 1.12, 95% CI = 0.87-1.46; recessive model: OR = 1.27, 95% CI = 0.89-1.82). Similarly, subgroup analysis including studies consistent with the Hardy-Weinberg equilibrium revealed no association between the IL1B polymorphism and BD susceptibility. Conclusion This meta-analysis indicates that the IL1B -511C/T polymorphism is unlikely to affect the risk of BD; however, further large-scale, carefully designed studies are needed to verify these results.

Neoadjuvant chemotherapy (NAC) may increase the resection rate of breast cancer and shows promising effects on patient prognosis. It has become a necessary treatment choice and is widely used in the clinical setting. Benefitting from the clinical information obtained during NAC treatment, computational methods can improve decision-making by evaluating and predicting treatment responses using a multidisciplinary approach, as there are no uniformly accepted protocols for all institutions for adopting different treatment regiments. In this study, 166 Chinese breast cancer cases were collected from patients who received NAC treatment at the First Bethune Hospital of Jilin University. The Miller–Payne grading system was used to evaluate the treatment response. Four machine learning multiple classifiers were constructed to predict the treatment response against the 26 features extracted from the patients’ clinical data, including Random Forest (RF) model, Convolution Neural Network (CNN) model, Support Vector Machine (SVM) model, and Logistic Regression (LR) model, where the RF model achieved the best performance using our data. To allow a more general application, the models were reconstructed using only six selected features, and the RF model achieved the highest performance with 54.26% accuracy. This work can efficiently guide optimal treatment planning for breast cancer patients.

Background Many studies have investigated the relationship between the interleukin-1β gene ( IL1B ) −511C/T polymorphism and the risk of Behçet’s disease (BD); however, the conclusions remain controversial. Methods In this study, we systemically retrieved relevant studies from the Chinese Biomedicine Database, China National Knowledge Infrastructure, Embase, Cochrane Library, and PubMed databases. We then calculated the odds ratios (ORs) and 95% confidence intervals (CIs) using the meta-package Stata version 12.0. Results The IL1B −511C/T polymorphism was not related to BD susceptibility using any of the tested models (C vs T: OR = 1.20, 95% CI = 0.97–1.49; CC vs TT: OR = 1.27, 95% CI = 0.95–1.70; CT vs TT: OR = 1.03, 95% CI = 0.781.36; dominant model: OR = 1.12, 95% CI = 0.87–1.46; recessive model: OR = 1.27, 95% CI = 0.89–1.82). Similarly, subgroup analysis including studies consistent with the Hardy–Weinberg equilibrium revealed no association between the IL1B polymorphism and BD susceptibility. Conclusion This meta-analysis indicates that the IL1B −511C/T polymorphism is unlikely to affect the risk of BD; however, further large-scale, carefully designed studies are needed to verify these results. Keywords Interleukin-1β , Behçet’s disease , meta-analysis , gene polymorphism , risk factor , genetic susceptibility

Background Many studies have investigated the relationship between the interleukin-1β gene ( IL1B ) −511C/T polymorphism and the risk of Behçet’s disease (BD); however, the conclusions remain controversial. Methods In this study, we systemically retrieved relevant studies from the Chinese Biomedicine Database, China National Knowledge Infrastructure, Embase, Cochrane Library, and PubMed databases. We then calculated the odds ratios (ORs) and 95% confidence intervals (CIs) using the meta-package Stata version 12.0. Results The IL1B −511C/T polymorphism was not related to BD susceptibility using any of the tested models (C vs T: OR = 1.20, 95% CI = 0.97–1.49; CC vs TT: OR = 1.27, 95% CI = 0.95–1.70; CT vs TT: OR = 1.03, 95% CI = 0.781.36; dominant model: OR = 1.12, 95% CI = 0.87–1.46; recessive model: OR = 1.27, 95% CI = 0.89–1.82). Similarly, subgroup analysis including studies consistent with the Hardy–Weinberg equilibrium revealed no association between the IL1B polymorphism and BD susceptibility. Conclusion This meta-analysis indicates that the IL1B −511C/T polymorphism is unlikely to affect the risk of BD; however, further large-scale, carefully designed studies are needed to verify these results.

Oxidative stress, which refers to unbalanced accumulation of reactive oxygen species (ROS) levels in cells, has been linked to acute and chronic diseases. Nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway plays a vital role in regulating cytoprotective genes and enzymes in response to oxidative stress. Therefore, pharmacological regulation of Nrf2/ARE pathway is an effective method to treat several diseases that are mainly characterized by oxidative stress and inflammation. Natural products that counteract oxidative stress by modulating Nrf2 have contributed significantly to disease treatment. In this review, we focus on bioactive compounds derived from food that are Nrf2/ARE pathway regulators and describe the molecular mechanisms for regulating Nrf2 to exert favorable effects in experimental models of diseases.

Background Aspirin use has been suggested to reduce the incidence of ovarian cancer (OC) in women. However, previous studies regarding the association between aspirin use and mortality in women with OC showed inconsistent results. We aimed to evaluate the association between aspirin use and mortality in women with OC in a meta-analysis. Methods Relevant cohort studies were obtained via search of PubMed, Cochrane’s Library, and Embase databases from inception to May 3, 2020. A random-effect model, which incorporates the potential heterogeneity among the included studies, was used to pool the results. Predefined stratified analyses were applied to evaluate the potential study characteristics on the outcome, including the timing of aspirin use, dose of aspirin, age of the women, and the clinical stages of the cancer. Sensitivity analysis by omitting one study at a time was used to assess the stability of the results. Results Six cohort studies including 17,981 women with OC were included. Pooled results showed that aspirin use had no statistically significant association with mortality in these patients (adjusted risk ratio [RR]: 0.85, 95% confidence interval [CI]: 0.70 to 1.02, p = 0.08; I2 = 69%). The results were similar for OC-specific mortality (RR: 0.85, 95% CI: 0.57 to 1.26, p = 0.41) and all-cause mortality (RR: 0.78, 95% CI: 0.55 to 1.11, p = 0.17). Stratified analyses suggested that aspirin use had no statistically significant association with mortality risk in OC regardless the timing of aspirin use, dose of aspirin, age of the women, or the clinical stages of the cancer. Funnel plots suggested potential risk of publication bias (p all > 0.05). However, further “trim-and-fill” analysis incorporating hypothesized unpolished studies to achieve symmetrical funnel plots showed similar results of the meta-analysis (RR: 0.91, 95% CI: 0.74 to 1.13, p = 0.39). Conclusions Current evidence from observational studies indicated that aspirin use had no statistically significant association with mortality in women with OC.

The survival benefits of neoadjuvant chemotherapy (NAC) compared with those of concurrent chemoradiotherapy (CRT) for locally advanced cervical cancer (LACC) patients remain uncertain. Meta-analysis was used to compare NAC and CRT. A systematic search was performed up to 9 September 2020. Survival outcomes were analyzed based on event frequency or hazard ratios (HRs). Multilevel mixed-effects logistic regression was applied to analyze the effect of regimen variables on survival outcomes. Analysis based on Cox regression showed that CRT was better than NAC + radical hysterectomy (RT) (HR 1.25; 95% confidence interval (CI)) 1.02–1.54; p = 0.034) in terms of overall survival (OS). According to multilevel mixed-effects model analysis comparing NAC + RT and CRT, LACC patients who used cisplatin instead of carboplatin had a better Progression-free survival (PFS) (odds ratio (OR) 1.54; 95% CI 1.08–2.20; p = 0.016). When NAC + CRT and CRT were compared, gemcitabine administration was associated with a decrease in PFS (OR 0.47; 95% CI 0.22–0.99; p = 0.047). Increased doses of cisplatin and paclitaxel were associated with survival improvement. Based on traditional meta-analysis, CRT was better than NAC + RT in terms of OS. Carboplatin instead of cisplatin as part of the NAC + RT strategy or gemcitabine use in NAC + CRT may not be a good choice. An increased total dosage of paclitaxel and/or cisplatin as part of NAC + CRT and CRT strategies may improve the survival outcome of LACC patients.

目的 分析晚期上皮性卵巢癌患者5年生存率的影响因素.方法 选取2010年1月-2014年1月就诊于吉林大学白求恩第一医院的183例晚期上皮性卵巢癌患者,按生存时间将患者分为生存期≥5年组(56例)和生存期＜5年组(127例),分析晚期上皮性卵巢癌患者5年生存率的影响因素.结果 年龄、术后残余病灶≤1 cm、组织分级、无铂间期＞6个月、单核细胞与淋巴细胞比值(MLR) ＜0.15是晚期上皮性卵巢癌患者5年生存率的独立危险因素.结论 对卵巢癌高危人群定期体检可以提高早期诊断率,晚期卵巢癌患者行满意的肿瘤细胞减灭术并辅以规范的临床治疗可以改善预后,而年龄、术后残余病灶、组织分级、无铂间期、MLR等与患者的预后相关,可以作为评估晚期卵巢癌患者预后的指标.

Mesenchymal stem/stromal cells (MSCs) have been identified in almost all adult human tissues and been used in numerous clinical trials for a variety of diseases. Studies have shown that MSCs would undergo cellular senescence when cultured over a long term, which is brought on by increased epigenetic modifications, including DNA methylation. However, the mechanism of MSCs senescence is not well studied. In this study, the effects of RG108, a DNA methyltransferase inhibitor (DNMTi), on senescence, apoptosis, and pluripotency gene expressions in porcine bone marrow (pBM)-MSCs were investigated. First, we determined the optimized dose and time of RG108 treatment in pBM-MSCs to be 10 mu M for 48 hours, respectively. Under these conditions, the pluripotency genes (NANOG, POU5F1), the anti-senescence genes (TERT, bFGF), and the anti-apoptosis gene (BCL2) were increased, whereas the apoptotic gene (BAX) was decreased. RG108 protected against apoptosis when pBM-MSC induces apoptosis with H2O2 for 1.5 hours. We also found that RG108 significantly induced the expression of NANOG and POU5F1 by decreasing DNA methylation in gene promoter regions. These results indicate that an optimized dose of RG108 may promote the pluripotency-related character of pBM-MSCs through improving cellular anti-senescence, anti-apoptosis, and pluripotency, which provide a better cell origin for stem cell therapy.

New Findings What is the central question of this study? The aim was to investigate the function of microRNA‐188 in the biological characteristics of lung cancer stem cells and the molecular mechanisms involved. What is the main finding and its importance? This study highlights a new molecular mechanism involving microRNA‐188, MDK and the Hippo signalling pathway that plays a suppressive role in biological activity of lung cancer stem cells. This finding might offer new insights into gene‐based therapy for lung cancer. AbstractMicroRNAs (miRNAs) have been implicated in lung cancer and reported as new promising diagnostic and therapeutic tools for cancer control. Here, we investigated the action of microRNA‐188 (miR‐188) in lung cancer stem cells. We first tested miR‐188 expression in clinical samples of lung cancer patients, and a low expression profile of miR‐188 was found. Next, we analysed the role of miR‐188 in lung cancer stem cells with cell growth assays. To verify the in vitro results, we used a xenograft model to validate the capability of miR‐188 in tumorigenesis. Overexpression of miR‐188 reduced viability and metastasis of cancer stem cells. Similar results were reproduced in vivo, where overexpression of miR‐188 retarded tumour growth in mice. We also identified MDK as a target of miR‐188, and overexpression of MDK was found in lung cancer samples. Overexpressed MDK promoted the malignant behaviours of lung cancer stem cells. In addition, the Hippo pathway was found to be inactivated in lung cancer tissues, presenting as increased levels of YAP and TAZ. Suppression of the Hippo pathway also enhanced lung cancer stem cell activity and promoted the growth of xenograft tumours. To sum up, our results reveal that miR‐188 inhibits the malignant behaviours of lung cancer stem cells and the growth of xenograft tumours. This study might offer new insights into gene‐based therapies for cancer.