Distinct cytokine profiles in patients with preeclampsia.

OBJECTIVE: Preeclampsia (PE) is a common but serious pregnancy complication that adversely affects both maternal and fetal health. However, the mechanisms of its pathogenesis remain unclear, and effective biomarkers for early diagnosis are still lacking. METHODS: In this retrospective study, comprehensive bioinformatic analysis and logistic regression analysis were used to compare profiles of 48 serum cytokines in 27 PE patients with those in 41 normotensive pregnant subjects. RESULTS: The results revealed that serum cytokine profiles accumulated to different levels between the two groups, which had significant correlations with the clinical features of PE. Nine cytokines with high discriminatory capacity for diagnosising PE (AUC ≥ 0.7) were selected for inclusion in a multivariate logistic regression model for PE and calculated as a probability diagnostic formula. This model constructed from the panel of nine cytokines had better diagnostic performance than any individual cytokine (AUC = 0.97, 95% CI 0.94-1.00, P < 0.0001), with a sensitivity of 96.30% and a specificity of 90.24%. CONCLUSIONS: The set of cytokine profiles and risk assessment model described here can serve as a basis for developing early clinical diagnostic and therapeutic strategies for PE.

Activin A increases human trophoblast invasion by upregulating integrin ß1 through ALK4.

Activin A promotes human trophoblast invasion during the first trimester of pregnancy and is associated with preeclampsia and pregnancy-induced hypertension (PE/PIH) in naturally conceived pregnancies. However, whether integrin ß1 mediates activin A-increased trophoblast invasion remains unknown and the evidence is limited regarding the predictive value of activin A for PE/PIH in women receiving in vitro fertilization (IVF) treatment. Here, we studied the role and underlying molecular mechanisms of integrin ß1 in activin A-promoted invasion in immortalized (HTR8/SVneo) and primary human extravillous trophoblast (EVT) cells. A nest case-control study was designed to investigate the predictive/diagnostic value of activin A in IVF pregnancies. Results showed that integrin ß1 expression increased after activin A treatment and knockdown of integrin ß1 significantly decreased both basal and activin A-increased HTR8/SVneo cell invasion. SB431542 (TGF-ß type I receptors inhibitor) abolished activin A-induced SMAD2/SMAD3 phosphorylation and integrin ß1 overexpression. Activin A-upregulated integrin ß1 expression was attenuated after the depletion of ALK4 or SMAD4 in both HTR8/SVneo and primary EVT cells. Furthermore, we found similar first-trimester activin A levels in IVF patients with or without subsequent PE/PIH. These results reveal that integrin ß1 mediates activin A-promoted trophoblast invasion through ALK4-activated SMAD2/3-SMAD4 pathway, and the predictive/diagnostic value of first-trimester maternal serum activin A for hypertensive disorders of pregnancy might be different in IVF population.

Potential Role of Quercetin in Polycystic Ovary Syndrome and Its Complications: A Review.

Polycystic ovary syndrome (PCOS) is a common multisystem disease with reproductive, metabolic and psychological abnormalities. It is characterized by a high prevalence rate in women of childbearing age and highly heterogeneous clinical manifestations, which seriously harm women's physical and mental health. Quercetin (QUR) is a natural compound of flavonoids found in a variety of foods and medicinal plants. It can intervene with the pathologic process of PCOS from multiple targets and channels and has few adverse reactions. It is mentioned in this review that QUR can improve ovulation disorder, relieve Insulin resistance (IR), reduce androgen, regulate lipid metabolism, regulate gut microbiota and improve vascular endothelial function, which is of great significance in the treatment of PCOS.

Risk factors for catheter-associated urinary tract infection among hospitalized patients: A systematic review and meta-analysis of observational studies.

AIMS: The study aimed to identify the risk factors for catheter-associated urinary tract infection among hospitalized patients. We also tried to explore its potential effect on patient outcomes if possible. BACKGROUND: Catheter-associated urinary tract infection accounts for a large proportion of healthcare-associated infections and remains a considerable threat to patient safety worldwide. DESIGN: A systematic review and meta-analysis of observational studies. DATA SOURCES: We conducted an electronic search in PubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews for studies published between January 2008-January 2018. REVIEW METHODS: Two reviewers searched the articles and extracted the data independently. The quality of the studies was assessed with the Newcastle-Ottawa Scale. RevMan 5.3 was used to perform the meta-analysis. RESULTS: Ten studies involving a total of 8785 participants with or without catheter-associated urinary tract infection were included. The average incidence of catheter-associated urinary tract infection was 13.79 per 1000 catheter days, with a prevalence rate of 9.33%. The meta-analysis demonstrated that patients at high risk for catheter-associated urinary tract infection were female, had a prolonged duration of catheterization, had diabetes, had previous catheterization, and had longer hospital and ICU stays. Additionally, catheter-associated urinary tract infection was also accompanied by an increase in mortality. CONCLUSIONS: Healthcare staff should focus on the identified risk factors for catheter-associated urinary tract infection. Further research is needed to investigate the microbial isolates and focus on the intervention strategies of catheter-associated urinary tract infection, so as to reduce its incidence and related mortality.

Hyper-acetylation contributes to the sensitivity of chemo-resistant prostate cancer cells to histone deacetylase inhibitor Trichostatin A.

Therapeutic agents are urgently needed for treating metastatic castration-refractory prostate cancer (mCRPC) that is unresponsive to androgen deprivation and chemotherapy. Our screening assays demonstrated that chemotherapy-resistant prostate cancer (PCa) cells are more sensitive to HDAC inhibitors than paired sensitive PCa cells, as demonstrated by cell proliferation and apoptosis in vitro and in vivo. Kinetic study revealed that TSA-induced apoptosis was significantly dependent on enhanced transcription and protein synthesis in an early stage, which subsequently caused ER stress and apoptosis. ChIP analysis indicated that TSA increased H4K16 acetylation, promoting ER stress gene transcription. The changes in Ac-H4K16, ATF3 and ATF4 were also validated in TSA-treated animals. Further study revealed the higher enzyme activity of HDACs and an increase in acetylated proteins in resistant cells. The higher nucleocytoplasmic acetyl-CoA in resistant cells was responsible for elevated acetylation status of protein and a more vigorous growth state. These results strongly support the pre-clinical application of HDAC inhibitors for treating chemotherapy-resistant mCRPC.

Real-Time Tracking and In Vivo Visualization of ß-Galactosidase Activity in Colorectal Tumor with a Ratiometric Near-Infrared Fluorescent Probe.

Development of "smart" noninvasive bioimaging probes for trapping specific enzyme activities is highly desirable for cancer therapy in vivo. Given that ß-galactosidase (ß-gal) is an important biomarker for cell senescence and primary ovarian cancers, we design an enzyme-activatable ratiometric near-infrared (NIR) probe (DCM-ßgal) for the real-time fluorescent quantification and trapping of ß-gal activity in vivo and in situ. DCM-ßgal manifests significantly ratiometric and turn-on NIR fluorescent signals simultaneously in response to ß-gal concentration, which makes it favorable for monitoring dynamic ß-gal activity in vivo with self-calibration in fluorescent mode. We exemplify DCM-ßgal for the ratiometric tracking of endogenously overexpressed ß-gal distribution in living 293T cells via the lacZ gene transfection method and OVCAR-3 cells, and further realize real-time in vivo bioimaging of ß-gal activity in colorectal tumor-bearing nude mice. Advantages of our system include light-up ratiometric NIR fluorescence with large Stokes shift, high photostability, and pH independency under the physiological range, allowing for the in vivo real-time evaluation of ß-gal activity at the tumor site with high-resolution three-dimensional bioimaging for the first time. Our work provides a potential tool for in vivo real-time tracking enzyme activity in preclinical applications.

Far-Red and Near-IR AIE-Active Fluorescent Organic Nanoprobes with Enhanced Tumor-Targeting Efficacy: Shape-Specific Effects.

The rational design of high-performance fluorescent materials for cancer targeting in vivo is still challenging. A unique molecular design strategy is presented that involves tailoring aggregation-induced emission (AIE)-active organic molecules to realize preferable far-red and NIR fluorescence, well-controlled morphology (from rod-like to spherical), and also tumor-targeted bioimaging. The shape-tailored organic quinoline-malononitrile (QM) nanoprobes are biocompatible and highly desirable for cell-tracking applications. Impressively, the spherical shape of QM-5 nanoaggregates exhibits excellent tumor-targeted bioimaging performance after intravenously injection into mice, but not the rod-like aggregates of QM-2.

Construction of a predictive model for postoperative hospitalization time in colorectal cancer patients based on interpretable machine learning algorithm: a prospective preliminary study.

Objective: This study aims to construct a predictive model based on machine learning algorithms to assess the risk of prolonged hospital stays post-surgery for colorectal cancer patients and to analyze preoperative and postoperative factors associated with extended hospitalization. Methods: We prospectively collected clinical data from 83 colorectal cancer patients. The study included 40 variables (comprising 39 predictor variables and 1 target variable). Important variables were identified through variable selection via the Lasso regression algorithm, and predictive models were constructed using ten machine learning models, including Logistic Regression, Decision Tree, Random Forest, Support Vector Machine, Light Gradient Boosting Machine, KNN, and Extreme Gradient Boosting, Categorical Boosting, Artificial Neural Network and Deep Forest. The model performance was evaluated using Bootstrap ROC curves and calibration curves, with the optimal model selected and further interpreted using the SHAP explainability algorithm. Results: Ten significantly correlated important variables were identified through Lasso regression, validated by 1000 Bootstrap resamplings, and represented through Bootstrap ROC curves. The Logistic Regression model achieved the highest AUC (AUC=0.99, 95% CI=0.97-0.99). The explainable machine learning algorithm revealed that the distance walked on the third day post-surgery was the most important variable for the LR model. Conclusion: This study successfully constructed a model predicting postoperative hospital stay duration using patients' clinical data. This model promises to provide healthcare professionals with a more precise prediction tool in clinical practice, offering a basis for personalized nursing interventions, thereby improving patient prognosis and quality of life and enhancing the efficiency of medical resource utilization.

Association of bevacizumab and stroke in ovarian cancer: a systematic review and meta-analysis.

Background: The prognosis for patients with ovarian cancer is bleak. Clinical trials have shown the efficacy of bevacizumab in ovarian cancer treatment. However, life-threatening strokes may limit the usage of bevacizumab and require specific follow-up strategies. This study aims to systematically evaluate the risk of stroke of bevacizumab treatment in ovarian cancer. Methods: We retrieved all relevant articles published up to December 4th, 2022, from Embase, PubMed, Web of Science, and the Cochrane Library. The risk of stroke in patients with ovarian cancer treated with bevacizumab combined with chemotherapy was analyzed. Meta-analysis was performed using the Stata 17 software and R 4.2.1 program. Results: Six randomized controlled trials (RCTs) of bevacizumab combined with chemotherapy or chemotherapy for ovarian cancer and six single-experimental-arm trials were included in this study. The meta-analysis showed a pooled risk ratio (RR) of 2.14 [95% confidence interval (CI): 0.88-7.99] for patients with ovarian cancer treated with bevacizumab combined with chemotherapy. Subgroup analyses showed that the incidence of stroke-related adverse events in the carboplatin + paclitaxel + bevacizumab group was 0.01% (95% CI: 0.00-0.01, p < 0.01). The incidence of stroke-related adverse events was 0.01% (95% CI: 0.00-0.01, p < 0.01) in patients aged ≥60. The incidence of stroke caused by cerebral ischemia and cerebral hemorrhage was 0.01% (95% CI: 0.01-0.02, p = 0.27) and 0.01% (95% CI: 0.00-0.01, p < 0.01), respectively. Conclusions: This meta-analysis indicates that chemotherapy combined with bevacizumab may not increase the incidence of stroke in patients with ovarian cancer. However, stroke-related adverse events may be higher in older patients. Cerebral hemorrhage might cause the incidence of stroke more than cerebral ischemia. Systematic review registration: PROSPERO (CRD42022381003).

Polycystic ovary syndrome and 25-hydroxyvitamin D: A bidirectional two-sample Mendelian randomization study.

Background: Accumulating observational studies have indicated that vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) < 50 nmol/L) is common in women with polycystic ovary syndrome (PCOS). However, the direction and causal nature remain unclear. In this study, we aimed to investigate the causal association between PCOS and 25OHD. Methods: A bidirectional two-sample Mendelian randomization (MR) study was used to evaluate the causal association between PCOS and 25OHD. From the publicly available European-lineage genome-wide association studies (GWAS) summary statistics for PCOS (4,890 cases of PCOS and 20,405 controls) and 25OHD (n = 417,580), we selected 11 and 102 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs), respectively. In univariate MR (uvMR) analysis, inverse-variance weighted (IVW) method was employed in the primary MR analysis and multiple sensitivity analyses were implemented. Additionally, a multivariable MR (mvMR) design was carried to adjust for obesity and insulin resistance (IR) as well. Results: UvMR demonstrated that genetically determined PCOS was negatively associated with 25OHD level (IVW Beta: -0.02, P = 0.008). However, mvMR found the causal effect disappeared when adjusting the influence of obesity and IR. Both uvMR and mvMR analysis didn't support the causal effect of 25OHD deficiency on risk of PCOS (IVW OR: 0.86, 95% CI: 0.66 ~ 1.12, P = 0.280). Conclusion: Our findings highlighted that the casual effect of PCOS on 25OHD deficiency might be mediated by obesity and IR, and failed to find substantial causal effect of 25OHD deficiency on risk of PCOS. Further observational studies and clinical trials are necessary.

First-Trimester Serum Cytokine Profile in Pregnancies Conceived After Assisted Reproductive Technology (ART) With Subsequent Pregnancy-Induced Hypertension.

Pregnancy-induced hypertension (PIH) is one of the most common pregnancy complications that seriously affects the mother and fetus. The incidence of PIH is higher in pregnancies conceived after assisted reproductive technology (ART) than in spontaneous pregnancies; thus, exploring potential serum biomarkers before PIH onset is of great significance for effective early prediction and prevention of PIH in the ART population. Cytokines are involved in the inflammatory response and immune regulation, which play an essential role in the pathogenesis of PIH. A description of the cytokine profile in the first trimester of pregnancy could help identify new diagnostic tools and develop targeted therapies for PIH in the ART population. The concentrations of classical predictive markers for PIH and another 48 cytokines were measured in the first-trimester pregnancy serum samples from 33 PIH patients and 33 matched normotensive controls (NC), both of whom conceived after ART treatment. The measured values were compared and analyzed between NC and PIH, followed by comprehensive bioinformatic analysis and logistic regression analysis. There was no significant difference in classical predictive markers, including Activin A, PlGF, sFLT1 (VEGFR), and sFLT1/PlGF, between the PIH and NC groups (P > 0.05), while 29 cytokines were significantly lower in the PIH group than in the NC group (P < 0.05). Logistic regression analysis revealed that 17 cytokines (IL-2Rα, M-CSF, IL-6, IL-2, ß-NGF, IL-7, IL-12 (p70), SCF, IL-10, IL-9, MIG, GM-CSF, LIF, IL-1α, MCP-3, IL-4, and HGF) in the first-trimester pregnancy serum were significantly negatively correlated with the subsequent onset of PIH. With the top 3 cytokines (IL-7, MIG, and SCF) of receiver operating characteristic (ROC) analysis, we constructed an efficient multifactor combined detection and prediction model for PIH in ART pregnancy. Classical early predictors for hypertensive disorder complicating pregnancy cannot distinguish PIH from their normal peers in ART pregnancy. In comparison, the description of the cytokine profile in the first trimester of pregnancy enables us to distinguish high-risk ART pregnancy for PIH, permitting enough time for PIH prevention therapy. The cytokine profile we described also provides immunological insight into the further mechanistic exploration of PIH.

Modified Banxia Xiexin Decoction Ameliorates Polycystic Ovarian Syndrome With Insulin Resistance by Regulating Intestinal Microbiota.

Objective: To analyze the characteristics of the intestinal microbiota of polycystic ovarian syndrome with insulin resistance (PCOS-IR) and explore the possible mechanism of modified Banxia Xiexin Decoction in the treatment of PCOS-IR. Methods: A total of 17 specific pathogen-free (SPF) female Sprague-Dawley (SD) rats, aged 21 days, were selected and randomly divided into the control group (group Z, n = 6), model group (group M, n = 6), and treatment group (group A, n = 5). Letrozole combined with a high-fat diet was used to induce the PCOS-IR model. Rats in group A were treated with modified Banxia Xiexin Decoction for 2 weeks after the end of modeling; then the characteristics of reproductive, metabolic, inflammatory, and intestinal microbiota were compared among three groups. Results: The PCOS-IR model had an imbalance of intestinal microbiota, and the enriched microbiota was mainly class Coriobacteria, order Clostridiales, and genus Clostridium_sensu_stricto_1. Modified Banxia Xiexin Decoction can regulate the disorder of intestinal microbiota diversity, significantly increase the abundance of phyla Verrucomicrobiota Proteobacteria and genera Akkermansia and Blautia, and decrease the abundance of genus Clostridium_sensu_stricto_1. Conclusion: Genus Clostridium_sensu_stricto_1 might be the pivotal pathogenic bacteria of PCOS-IR. Modified Banxia Xiexin Decoction may ameliorate PCOS-IR by regulating intestinal microbiota imbalance and improving metabolic disorders.

MicroRNA-153-5p promotes the proliferation and metastasis of renal cell carcinoma via direct targeting of AGO1.

MicroRNAs (miRNAs) have been demonstrated to affect the biological processes of cancers and showed great potential for prognostic biomarkers. In this study, we screened differentially expressed miRNAs in ccRCC based on three dimensions of metastasis, prognosis, and differential expression compared to normal tissue using bioinformatics algorithms. MiR-153-5p was identified as a candidate miRNA to promote ccRCC occurrence and progression. Clinically, we found that miR-153-5p was significantly upregulated and related to unfavorable clinical features in ccRCC. Besides, miR-153-5p served as an independent prognostic biomarker. Functionally, miR-153-5p depletion remarkably inhibited the proliferation and metastasis of ccRCC via the phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Furthermore, AGO1 was proved to be a direct target of miR-153-5p. AGO1 is associated with favorable clinical features and exhibited independent prognostic value in ccRCC. Besides, we observed that AGO1 knockdown significantly promoted tumor proliferation and metastasis. Downregulation of AGO1 partly abolished the oncogenic effects of miR-153-5p knockdown. Furthermore, miR-153-5p combined with AGO1 showed more robust prognostic significance in ccRCC. In conclusion, we found that the newly identified miR-153-5p/AGO1 axis was responsible for tumor occurrence and progression via PI3K/Akt signaling, which may therefore provide promising therapeutic targets and prognostic biomarkers for patients with ccRCC.

Imaging-Based Body Fat Distribution in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Background: Women with polycystic ovary syndrome (PCOS) are generally considered to be central obese and at higher risks of metabolic disturbances. Imaging methods are the golden standards for detecting body fat distribution. However, evidence based on magnetic resonance imaging (MRI) and computed tomography (CT) is conflicting. This study systematically reviewed the imaging-based body fat distribution in PCOS patients and quantitatively evaluated the difference in body fat distribution between PCOS and BMI-matched controls. Methods: PUBMED, EMBASE, and Web of Science were searched up to December 2019, and studies quantitatively compared body fat distribution by MRI, CT, ultrasound, or X-ray absorptiometry (DXA) between women with PCOS and their BMI-matched controls were included. Two researchers independently reviewed the articles, extract data and evaluated the study quality based on Newcastle-Ottawa Scale (NOS). Results: 47 studies were included in systematic review and 39 were eligible for meta-analysis. Compared to BMI-matched controls, higher accumulations of visceral fat (SMD 0.41; 95%CI: 0.23-0.59), abdominal subcutaneous fat (SMD 0.31; 95%CI: 0.20-0.41), total body fat (SMD 0.19; 95% CI: 0.06-0.32), trunk fat (SMD 0.47; 95% CI: 0.17-0.77), and android fat (SMD 0. 36; 95% CI: 0.06-0.66) were identified in PCOS group. However, no significant difference was identified in all the above outcomes in subgroups only including studies using golden standards MRI or CT to evaluate body fat distribution (SMD 0.19; 95%CI: -0.04-0.41 for visceral fat; SMD 0.15; 95%CI: -0.01-0.31 for abdominal subcutaneous fat). Moreover, meta-regression and subgroup analyses showed that young and non-obese patients were more likely to accumulate android fat. Conclusions: PCOS women seem to have abdominal fat accumulation when compared with BMI-matched controls. However, MRI- and CT- assessed fat distribution was similar between PCOS and controls, suggesting central obesity may be independent of PCOS. These findings will help us reappraise the relationship between PCOS and abnormal fat deposition and develop specialized lifestyle interventions for PCOS patients. Systematic Review Registration: PROSPERO, identifier CRD42018102983.

The effect of CPAP and PDE5i on erectile function in men with obstructive sleep apnea and erectile dysfunction: A systematic review and meta-analysis.

Growing evidence has shown that obstructive sleep apnea (OSA) and erectile dysfunction (ED) often coexist. However, the effect of continuous positive airway pressure (CPAP) on erectile function remains controversial. The objective of this review was to clarify the anti-ED effect of CPAP and further compare the efficacy between CPAP, phosphodiesterase type 5 inhibitors (PDE5i) and combination therapy on erectile function in OSA patients concurrent ED. Literature search was performed up to December 1st, 2018 and 26 studies were included in the review. Results showed that CPAP significantly ameliorated the international index of erectile function (IIEF) score, total erectile events (TEE) and nocturnal penile rigidity (NPR), while no significant improvements in nocturnal penile tumescence circumference (NPTC). Moreover, CPAP was inferior to PDE5i in improving IIEF-erectile function, IIEF-intercourse satisfaction, NPTC, successful attempted intercourses rate (SAIR) and erectile dysfunction inventory of treatment satisfaction-question one (EDITS-Q1), while CPAP and PDE5i were of equal efficacy in other domains of IIEF and NPR. Interestingly, CPAP was more effective in improving TEE. Furthermore, CPAP combined with PDE5i was superior to CPAP alone in improving IIEF score, SAIR, and TEE. This review provided promising insights about CPAP-based ED treatment for OSA patients.

An enzyme-activatable probe liberating AIEgens: on-site sensing and long-term tracking of ß-galactosidase in ovarian cancer cells.

Development of fluorescent probes for on-site sensing and long-term tracking of specific biomarkers is particularly desirable for the early detection of diseases. However, available small-molecule probes tend to facilely diffuse across the cell membrane or remain at the activation site but always suffer from the aggregation-caused quenching (ACQ) effect. Here we report an enzyme-activatable aggregation-induced emission (AIE) probe QM-ßgal, which is composed of a hydrophilic ß-galactosidase (ß-gal)-triggered galactose moiety and a hydrophobic AIE-active fluorophore QM-OH. The probe is virtually non-emissive in aqueous media, but when activated by ß-gal, specific enzymatic turnover would liberate hydrophobic AIE luminogen (AIEgen) QM-OH, and then highly fluorescent nanoaggregates are in situ generated as a result of the AIE process, allowing for on-site sensing of endogenous ß-gal activity in living cells. Notably, taking advantage of the improved intracellular retention of nanoaggregates, we further exemplify QM-ßgal for long-term (∼12 h) visualization of ß-gal-overexpressing ovarian cancer cells with high fidelity, which is essential for biomedicine and diagnostics. Thus, this enzyme-activatable AIE probe not only is a potent tool for elucidating the roles of ß-gal in biological systems, but also offers an enzyme-regulated liberation strategy to exploit multifunctional probes for preclinical applications.

Metabolic disturbances in non-obese women with polycystic ovary syndrome: a systematic review and meta-analysis.

OBJECTIVE: To explore metabolic disturbances in nonobese women with polycystic ovary syndrome (PCOS) compared with nonobese healthy controls. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Nonobese women with PCOS and nonobese healthy controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Prevalence of metabolic disturbances including hyperinsulinemia, insulin resistance (IR), impaired fasting glucose (IFG), impaired glucose intolerance (IGT), prediabetes, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, and low high-density lipoprotein (low-HDL), as well as other metabolic outcomes such as type 2 diabetes mellitus (T2DM), hypertension, metabolic syndrome (Mets), myocardial infarction, stroke, cerebrovascular accident, arterial occlusive disease, and coronary heart disease. RESULT(S): Compared to nonobese controls, nonobese women with PCOS showed a higher prevalence of hyperinsulinemia (odds ratio [OR], 36.27; 95% confidence interval [CI] 1.76-747.12), IR (OR, 5.70; 95% CI 1.46-22.32), IGT (OR, 3.42; 95% CI 1.56-7.52), T2DM (OR, 1.47; 95% CI 1.11-1.93), hypertriglyceridemia (OR, 10.46; 95% CI 1.39-78.56), low-HDL (OR, 4.03; 95% CI 1.26-12.95), and Mets (OR, 2.57; 95% CI 1.30-5.07). No significant difference was observed for IFG, pre-DM, dyslipidemia, hypercholesterolemia, and hypertension. In subgroup analysis, Whites exhibited increased risks of IR, IGT, IFG, T2DM, hypertension, and Mets, whereas no significant metabolic change was found in Asians. No study reported specifically an incidence of myocardial infarction, stroke, cerebrovascular accident, arterial occlusive disease, and coronary heart disease in nonobese women with PCOS. CONCLUSION(S): Nonobese women with PCOS also suffer from metabolic disturbances and the risk of long-term metabolic complications. Further efforts should be made to elucidate underlying mechanisms and possible interventions in the early phase.

Nanomized tumor-microenvironment-active NIR fluorescent prodrug for ensuring synchronous occurrences of drug release and fluorescence tracing.

Improving the bioavailability and tumor-targeting ability of a prodrug, as well as monitoring its active ingredient release in vivo, is still a challenge in cancer diagnosis and therapy. Herein, a specific nanomized tumor-microenvironment-active near-infrared (NIR) fluorescent DCM-S-GEM/PEG prodrug was developed as a potent monitoring platform, wherein we conjugated antitumor drug gemcitabine (GEM) and NIR fluorescent chromophore dicyanomethylene-4H-pyran (DCM) via glutathione (GSH)-activatable disulfide linker and encapsulated DCM-S-GEM into an amphiphilic polymer DSPE-mPEG by self-assembly. The nanomized DCM-S-GEM/PEG prodrug exhibits excellent photostability and high biocompatibility, significantly improving the therapeutic efficacy toward lung tumor cells with fewer side-effects toward normal cells. Furthermore, when compared with the standalone DCM-S-GEM prodrug, the micellization with diblock DSPE-mPEG avoids fast metabolism, facilitates the accumulation of drugs in lung tumor tissues, displays longer tumor retention, and realizes precise drug release in lung tumors. The nanomized DCM-S-GEM/PEG prodrug can be developed as a promising tool to monitor prodrug delivery and activation processes in vivo.

Ethanol extract of Patrinia scabiosaefolia induces the death of human renal cell carcinoma 786-O cells via SIRT-1 and mTOR signaling-mediated metabolic disruptions.

Recently, natural plant extracts have shown tremendous potential as novel antitumor drugs. Patrinia scabiosaefolia, a traditional prescription for inflammatory diseases, has been reported to effectively suppress various types of cancers. However, the mechanisms underlying its antitumor properties remain elusive. In the present study, we investigated the antitumor effects of an ethanol extract of Patrinia scabiosaefolia (EPS) on human renal cell carcinoma 786-O cells. After 24 h of incubation with EPS, the cell viability and colony number of 786-O cells were significantly decreased in a concentration-dependent manner as compared to the control group as determined by MTT and colony formation assays, respectively. The necrotic rate and apoptotic rate in the EPS exposure group were significantly higher than these rates noted in the control group as revealed by LDH release assay and Hoechst 33342/ PI double staining, respectively. At the concentration of 1.0 mg/ml, the necrotic and apoptotic rates reached 41.7±6.6 and 7.8±1.4%, respectively (P<0.01). However, the fluorescence intensity of intracellular calcium concentration ([Ca2+]i) was markedly elevated from 0.029±0.0007 to 0.060±0.003 (P<0.001) after the intervention of EPS. Moreover, the fluorescence intensity of intracellular ROS in the EPS exposure group was significantly higher (0.074±0.005) compared to that observed in the control group (0.033±0.001, P<0.001), which was partly attenuated by the specific antioxidant N-acetylcysteine (NAC). Furthermore, our results demonstrated that EPS significantly downregulated the expression of SIRT-1 and obviously induced the dephosphorylation of mTOR. Moreover, combined treatment with the SIRT-1 inhibitor nicotinamide and EPS was able to significantly enhance the induction of necrosis and reduction in cell viability of 786-O cells noted following treatment with EPS alone. In summary, we conclude that EPS induced the death of 786-O cells via SIRT-1 and mTOR signaling-mediated metabolic disruptions, which provide novel insight into the application of natural plant extracts for the treatment of cancers.

Rational design of novel near-infrared fluorescent DCM derivatives and their application in bioimaging.

The development of innovative strategies for high-performance near-infrared (NIR) fluorescent materials is in urgent demand for bioimaging. By replacing the stronger electron-withdrawing groups or extending the π-conjugated system, novel NIR fluorescent materials of DCM analogues have been developed, along with several striking characteristics: bright NIR fluorescence over 700 nm, large Stokes shift and good photo-stability. It is demonstrated that introducing a stronger electron-withdrawing unit to the acceptor moiety of DCM analogues is a favourably efficient strategy to tune and prolong the emission wavelength into the NIR region with a large Stokes shift. In comparison with the commercial NIR dye ICG, S-DCM-N and S-DCM-P display excellent photostability and low photobleaching. The large Stokes Shift and NIR fluorescence channel of S-DCM-N and S-DCM-P are very favourable for fluorescence labelling with a high signal-to-noise ratio in living species.