Aliphatic hyperbranched polyphosphate: a novel multicolor RTP material with AIE character.

Long-lived photoluminescent probes are emerging as significant luminogens for biological imaging. However, currently, most long-lived luminescent materials contain expensive rare elements or cytotoxic bulky aromatic or conjugated units. Herein, a novel hyperbranched polyphosphate (HBPPE) was synthesized using triethyl phosphate (TEP) and ethylene glycol (EG) through a transesterification polycondensation reaction. The obtained HBPPE P1 can emit bright blue photoluminescence under UV light and show significant AIE character. Interestingly, the average photoluminescence lifetime of P1 is 12.82 µs. This suggests the first phosphorescent material without rare elements or aromatic structures attributed to the covalent-crystal-like structure. Besides, P1 shows an obvious red-shift along with the excitation wavelength, which emits blue, cyan, green, yellow and red photoluminescence, covering nearly all the visible light region. This study not only enriches the species of nonconventional multicolor AIE luminogens but also provides a concise method for the synthesis of HBPPE and demonstrates the possibility for phosphorescent materials without rare elements or bulky aromatic units.

Kisspeptin expression during menstruation in PCOS patients undergoing ovulation induction and the correlation with early pregnancy.

PURPOSE: To examine the pattern of kisspeptin expression throughout the menstrual cycle in polycystic ovary syndrome (PCOS) patients under the ovulation induction and identify any possible associations with early pregnancy. MATERIALS AND METHODS: A prospective cohort of 80 PCOS women who expressed the desire for fertility was enrolled in this study. All of them received the ovulation induction by using letrozole. Levels of kisspeptin, luteinizing hormone (LH), and estradiol (E2) were measured at three different time points during menstruation. The early pregnancy rate was recorded for the study participants after three ovulation cycles. RESULTS: Kisspeptin levels varied regularly during the menstrual cycle, reaching a peak on the day of hCG injection and decreasing after ovulation. There was no significant correlation between kisspeptin and LH levels. Basal kisspeptin levels decreased after letrozole treatment without a significant difference while LH and E2 levels decreased significantly. PCOS participants who became pregnant early had higher basal kisspeptin levels compared to non-pregnant PCOS patients, which had a significant difference (P = 0.006). And the average basal kisspeptin level in pregnant patients was 2293.0 ± 398.7 pg/ml, with a 95% confidence interval of 1511.5-3074.5 pg/ml. CONCLUSION: Kisspeptin levels in PCOS women undergoing ovulation induction showed a regular variation, which was similar with the healthy women reported in previous studies. The use of LE may result in PCOS endocrine improvement and fertility achievement. In a certain range, kisspeptin might be a potential predictor for early pregnancy in PCOS patients as people with slightly higher basal kisspeptin levels seemed more likely to be pregnant.

Risk Factors for Radical Rectal Cancer Surgery with a Temporary Stoma Becoming a Permanent Stoma: A Pooling Up Analysis.

Purpose: The aim of this study was to find out the potential risk factors for the formation of a permanent stoma (PS) for rectal cancer patients with a temporary stoma (TS) after surgery. Methods: PubMed, Embase, and the Cochrane Library were searched for eligible studies until November 14, 2022. The patients were divided into the PS group and the TS group. Odds ratio (ORs) and 95% confidence intervals (CIs) were pooled up for describing dichotomous variables. Stata SE 16 was performed for data analysis. Results: After pooling up the data, a total of 14 studies involving 14,265 patients were included in this study. The outcomes showed that age (OR = 1.03, 95% CI = 0.96 to 1.10, I2 = 1.42%, P = .00 < .1), surgery type (P = .00 < .1), tumor stage (P = .00 < .1), preoperative chemoradiotherapy (P = .00 < .1), preoperative radiotherapy (P = .01 < .1), neoadjuvant therapy (P = .00 < .1), American Society of Anesthesiologists (ASA) score of ≥3 (P = .00 < .1), anastomotic leakage (P = .01 < .1), local recurrence (P = .00 < .1), and distant recurrence (P = .00 < .1) were associated with the patient with PS. However, sex (P = .15 > .1), previous abdominal surgery (P = .84 > .1), adjuvant chemotherapy (P = .87 > .1), and defunctioning stoma (P = .1) had little association with PS. Conclusion: Patients who were elderly, had advanced tumor stages, had a high ASA score, and underwent neoadjuvant therapy should be informed of the high risk of PS before surgery. Meanwhile, those who underwent rectal cancer surgery with a TS should beware of anastomotic leakage, local recurrences, and distant recurrences, which could increase the risk of PS.

The advanced lung cancer inflammation index is a prognostic factor for gastrointestinal cancer patients undergoing surgery: a systematic review and meta-analysis.

BACKGROUND: The advanced lung cancer inflammation index (ALI) is a comprehensive assessment indicator that can reflect inflammation and nutrition conditions. However, there are some controversies about whether ALI is an independent prognostic factor for gastrointestinal cancer patients undergoing surgical resection. Thus, we aimed to clarify its prognostic value and explore the potential mechanisms. METHODS: Four databases including PubMed, Embase, the Cochrane Library, and CNKI were used for searching eligible studies from inception to June 28, 2022. All gastrointestinal cancers, including colorectal cancer (CRC), gastric cancer (GC), esophageal cancer (EC), liver cancer, cholangiocarcinoma, and pancreatic cancer were enrolled for analysis. We focused on prognosis most in the current meta-analysis. Survival indicators, including overall survival (OS), disease-free survival (DFS), and cancer-special survival (CSS) were compared between the high ALI group and the low ALI group. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was submitted as a supplementary document. RESULTS: We finally included fourteen studies involving 5091 patients in this meta-analysis. After pooling the hazard ratios (HRs) and 95% confidence intervals (CIs), ALI was found to be an independent prognostic factor for both OS (HR = 2.09, I2 = 92%, 95% CI = 1.53 to 2.85, P < 0.01), DFS (HR = 1.48, I2 = 83%, 95% CI = 1.18 to 1.87, P < 0.01), and CSS (HR = 1.28, I2 = 1%, 95% CI = 1.02 to 1.60, P = 0.03) in gastrointestinal cancer. After subgroup analysis, we found that ALI was still closely related to OS for CRC (HR = 2.26, I2 = 93%, 95% CI = 1.53 to 3.32, P < 0.01) and GC (HR = 1.51, I2 = 40%, 95% CI = 1.13 to 2.04, P = 0.006) patients. As for DFS, ALI also has a predictive value on the prognosis of CRC (HR = 1.54, I2 = 85%, 95% CI = 1.14 to 2.07, P = 0.005) and GC (HR = 1.37, I2 = 0%, 95% CI = 1.09 to 1.73, P = 0.007) patients. CONCLUSION: ALI affected gastrointestinal cancer patients in terms of OS, DFS, and CSS. Meanwhile, ALI was a prognostic factor both for CRC and GC patients after subgroup analysis. Patients with low ALI had poorer prognoses. We recommended that surgeons should perform aggressive interventions in patients with low ALI before the operation.

Laparoscopic versus open Hartmann reversal: a propensity score matching analysis.

PURPOSE: The purpose of this study was to compare the short-term outcomes between laparoscopic Hartmann reversal (LHR) and open Hartmann reversal (OHR) in patients who had undergone Hartmann surgery for colorectal cancer (CRC). METHODS: The patients who underwent Hartmann reversal (HR) at the First Affiliated Hospital of Chongqing Medical University from Jun 2013 to Jun 2022 were retrospectively enrolled. The LHR group and the OHR group were compared using propensity score matching (PSM) analysis. RESULTS: A total of 89 patients who underwent Hartmann reversal (HR) were enrolled in this study. There were 48 (53.9%) patients in the LHR group and 41 (46.1%) patients in the OHR group. After 1:1 ratio PSM, no difference in baseline information remained (p > 0.05). There was no significant difference in operation time, blood loss, postoperative hospital stay, and postoperative complications (p > 0.05) before and after PSM. In the multivariable logistic regression analysis, pre-operative albumin < 42.0 g/L was an independent risk factor (p = 0.013 < 0.05, OR = 0.248, 95% CI = 0.083-0.741) for the HR-related complications; however, LHR/OHR was not a predictive risk factor (p = 0.663, OR = 1.250, 95% CI = 0.500-3.122). CONCLUSION: Based on the current evidence, although there was no difference in short-term prognosis, LHR still had some advantages considering that it was less invasive to the patient.

Vascularized polypeptide hydrogel modulates macrophage polarization for wound healing.

Wound repair involves a sophisticated process that includes angiogenesis, immunoregulation and collagen deposition. However, weak revascularization performance and the lack of biochemical cues to trigger immunomodulatory function currently limit biomaterial applications for skin regeneration and tissue engineering. Herein, we fabricate a new bioactive polypeptide hydrogel (QK-SF) constituted by silk fibroin (SF) and a vascular endothelial growth factor mimetic peptide KLTWQELYQLKYKGI (QK) for tissue regeneration by simultaneously promoting vascularization and macrophage polarization. Our results showed that this QK-SF hydrogel can be prepared via an easy manufacturing process, and exhibited good gel stability and low cytotoxicity to cultured human umbilical vein endothelial cells (HUVECs) via both live/dead and cell counting kit-8 assays. Importantly, this QK-SF hydrogel triggered macrophage polarization from M1 into M2, as exemplified by the enhanced expression of the M2 marker and decreased expression of the M1 marker in RAW264.7 cells. Furthermore, the QK-SF hydrogel showed high capacity for inducing endothelial growth, migration and angiogenesis, which were proved by increased expression of angiogenesis-related genes in HUVECs. Consistent with in vitro findings, in vivo data show that the QK-SF hydrogel promoted M2 polarization, keratinocyte differentiation, and collagen deposition in the mouse skin wound model in immunohistochemistry assay. Furthermore, this QK-SF hydrogel can reduce inflammation, induce angiogenesis and promote wound healing as exemplified by the increased vessel formation and decreased wound area in the mouse skin wound model. Altogether, these results indicate that the bioactive QK-SF hydrogel plays dual functional roles in promoting angiogenesis and immunoregulation for tissue regeneration. STATEMENT OF SIGNIFICANCE: The QK-SF hydrogel plays dual functional roles in promoting angiogenesis and immunoregulation for tissue repair and wound healing. The QK-SF hydrogel can be prepared via an easy manufacturing process, and exhibited good gel stability and low cytotoxicity to cultured HUVECs. The QK-SF hydrogel triggered macrophage polarization from M1 into M2. The QK-SF hydrogel showed high capacity for inducing endothelial growth, migration and angiogenesis. The QK-SF hydrogel promoted M2 polarization, keratinocyte differentiation, and collagen deposition.

The Regulation of Trophoblastic p53 Homeostasis by the p38-Wip1 Feedback Loop is Disturbed in Placentas from Pregnancies Complicated by Preeclampsia.

BACKGROUND/AIMS: Excessive apoptosis of trophoblasts, induced by sustained hypoxia, leads to abnormal placentation and is strongly linked to pregnancy complications such as preeclampsia (PE). Wild-type p53-induced phosphatase (Wip1) positively regulates cellular survival in tumor cells through the p38 and p53 pathways, but its expression pattern and effects in trophoblasts have yet to be reported. This study clarified the effect of Wip1 on the regulatory mechanism of p53-dependent apoptosis in trophoblasts, and thus increases understanding of the etiology of PE. METHODS: In normal and PE placentas, Wip1 mRNA and protein levels were determined by RT-qPCR and Western blotting respectively, while localization of Wip1 in placental tissues and in HTR8/SVneo cells was determined by immunohistochemistry and immunofluorescence. Two in vitro trophoblastic PE models were established by subjecting HTR8/SVneo cells to either hypoxia intervention in incubator (HII) or simulated ischemic buffer (SIB). Wip1 was suppressed in the aforementioned PE models by specific inhibitor or shRNA, and apoptosis was then assessed by flow cytometry, while further validation was done by measurement of cleaved-caspase 9 expression by Western blotting. The p38 inhibitor SB202190, Mdm2 inhibitor NVP-CGM097, and proteasome inhibitor MG-132 were administered in PE models, either in combination or alone, to determine the regulatory order of the component signal molecules of the feedback loop. The impact of Wip1 on p53-Mdm2 interaction was examined by coimmunoprecipitation. Lastly, the upregulation of the p38-Wip1 loop was confirmed in human placentas from pregnancies complicated by PE, using Western blotting. RESULTS: Wip1 expression was significantly elevated in human PE placentas and in vitro trophoblastic PE models; this is opposite to the pattern observed in tumor cells. Inhibition of Wip1 rescued hypoxia-induced p38 activation, cleavage of caspase 9 and apoptosis but significantly compromised p53-Mdm2 binding, while p-p53Ser15 was increased. Inhibition of Mdm2 degradation resulted in p53 destabilization and p38-Wip1 loop down-regulation, while degradation of the p53-Mdm2 complex resulted in p53 accumulation and p38-Wip1 loop hyperactivation. However, the p53-Mdm2 interaction was found to be more important in the regulation of the p38-Wip1 loop than Mdm2 stability. CONCLUSION: Trophoblastic p53 homeostasis is maintained by the p38-Wip1 feedback regulatory loop in response to hypoxic stress, which is dysregulated in the placentas of pregnancies complicated by PE, and thereby leads to excessive apoptosis.

QSOX1 regulates trophoblastic apoptosis in preeclampsia through hydrogen peroxide production.

Objective: Oxidative stress plays a significant role in the pathogenesis of preeclampsia (PE), by inducing trophoblast cell death and consequent placental dysfunction. Quiescin sulfhydryl oxidase 1 (QSOX1) is upregulated in many types of cancer cells; it promotes disulfide bond formation as well as hydrogen peroxide (H2O2) production. The aims of present study are to investigate the expression pattern of QSOX1 in placentae of pregnancies complicated by PE and the role of QSOX1 in the regulation of trophoblastic function, thus providing in-depth understanding of the putative involvement of QSOX1 in the development of PE. Methods: Human term placenta from normal pregnancies and from pregnancies complicated by PE was collected to measure QSOX1 expression and H2O2 levels. Down-regulation of QSOX1 in HTR-8/SVneo cells was achieved by siRNA interference. An in vitro cellular PE model was generated by hypoxic incubation. Protein expression levels were assessed by Western blotting, and H2O2 levels were determined in the cell culture medium as well as in the cell lysate. Trophoblast apoptosis was evaluated by TUNEL staining. Results: QSOX1 was overexpressed in the PE placenta. Inhibition of QSOX1 expression in HTR-8/SVneo cells attenuated cell apoptosis and intracellular H2O2 levels. Hypoxia-induced QSOX1 expression in HTR-8/SVneo cells and led to apoptosis of HTR-8/SVneo cells, and knock-down of QSOX1 rescued hypoxia-induced trophoblast apoptosis. Conclusions: Hypoxia-induced upregulation of QSOX1 and a consequent elevation in intracellular H2O2 increased apoptosis in placentae of pregnancies complicated by PE.

Dietary n-3 polyunsaturated fatty acids, fish consumption, and endometrial cancer risk: a meta-analysis of epidemiological studies.

The relationship between intake of fish and n-3 fatty acids and endometrial cancer risk has not been consistent across epidemiological studies. We quantitatively assessed the aforementioned association through a systematic review and meta-analysis. PubMed and Embase were searched through March 2017 for eligible epidemiological studies. Fixed or random-effects models were used to pool relative risks (RRs) and 95% confidence intervals (CIs). The dose-response relationship was also evaluated. Based on the literature search, five prospective studies and 11 case-control studies were identified. All 16 studies were categorized as high-quality studies. After pooling available risk estimates, no significant association was detected between overall fish intake and endometrial cancer risk. In subgroup analyses, every one additional serving/week of fish intake was significantly associated with inversed endometrial cancer risk in studies adjusted for smoking (RR (95% CI): 0.95 (0.91-1.00)), or studies performed in Europe (RR (95% CI): 0.90 (0.84-0.97)), but not in other tested subgroups. In studies conducted in Asia, there was significant positive association (RR (95% CI): 1.15 (1.10-1.21)). Regarding n-3 PUFA intake, marginally inverse associations of high EPA or DHA intake were detected (EPA: RR (95% CI) = 0.79 (0.61-1.04); DHA: RR (95% CI) = 0.85 (0.64-1.11)). Dose-response analyses suggested a significant nonlinear relationship between DHA intake and endometrial cancer risk (p: 0.04). Overall, this meta-analysis suggests that intake of n-3 PUFA may be inversely associated with endometrial cancer risk at some level of evidence, although the exact relationship, especially for fish intake, needs further characterization. Further well-designed studies are warranted.

Smoking in pregnancy: a cross-sectional study in China.

BACKGROUND: Findings on smoking among pregnant women were mostly from high income countries and were rarely from China. This study aimed to estimate the prevalence of smoking and its influencing factors among pregnant women living in China. METHODS: A cross-sectional analysis was conducted in this study. Data from pregnant women were collected in this study from June to August 2015 from 5 provinces of mainland China. A total of 2345 pregnant women were included in this study, the mean age of the participants was 28.12 years (SD 4.13). RESULTS: About 82.9% of smoking women quit smoking after they were pregnant. The prevalence of smoking among pregnant women was 3.8%. Among the participants, 40.0, 30.7, 1.8, 29.9, 0.8, 31.4, 31.2, and 26.7% had husbands, fathers-in-law, mothers-in-law, fathers, mothers, colleagues, friends, and relatives, respectively, who were smokers. Compared with pregnant women of basic education level (junior middle school or below), those of the higher education level (undergraduate or above) were at higher risk of smoking (OR, 5.17; 95% CI, 2.00-13.39). Compared with pregnant women from rural areas, urban pregnant women were less likely to be current smokers (OR, 0.55; 95% CI, 0.32-0.94). Compared with pregnant women whose mothers-in-law did not smoke, those whose mothers-in-law smoked were at higher risk of smoking (OR, 4.67; 95% CI, 1.87-11.70). However, compared with pregnant women whose husband did not smoke, those whose husband smoked were not significantly at higher risk of smoking (OR, 1.12; 95% CI, 0.73-1.73). CONCLUSIONS: Most of smoking women quit smoking after they became pregnant. Tailored intervention programs to reduce smoking in pregnant women should focus on those with higher education level, from rural areas, and pregnant women whose mothers-in-law smoke.

Triethylenetetramine Synergizes with Pharmacologic Ascorbic Acid in Hydrogen Peroxide Mediated Selective Toxicity to Breast Cancer Cell.

Breast cancer is characterized by overexpression of superoxide dismutase (SOD) and downregulation of catalase and more resistance to hydrogen peroxide (H2O2) than normal cells. Thus, relatively high H2O2 promotes breast cancer cell growth and proliferation. However, excessive intracellular H2O2 leads to death of breast cancer cells. In cancer cells, high level ascorbic acid (Asc) is able to be autoxidized and thus provides an electron to oxygen to generate H2O2. In the present study, we demonstrated that triethylenetetramine (TETA) enhances Asc autoxidation and thus elevates H2O2 production in MCF-7 cells. Furthermore, Asc/TETA combination significantly impaired cancer cell viability, while having much milder effects on normal cells, indicating Asc/TETA could be a promising therapy for breast cancer. Moreover, SOD1 and N-acetyl-L-cysteine failed to improve MCF-7 cells viability in the presence of Asc/TETA, while catalase significantly inhibited the cytotoxicity of Asc/TETA to breast cancer cells, strongly suggesting that the selective cytotoxicity of Asc/TETA to cancer cells is H2O2-dependent. In addition, Asc/TETA induces RAS/ERK downregulation in breast cancer cells. Animal studies confirmed that Asc/TETA effectively suppressed tumor growth in vivo. In conclusion, TETA synergizes pharmacologic Asc autoxidation and H2O2 overproduction in breast cancer cells, which suppresses RAS/ERK pathway and results in apoptosis.

Altered Circulating Inflammatory Cytokines Are Associated with Anovulatory Polycystic Ovary Syndrome (PCOS) Women Resistant to Clomiphene Citrate Treatment.

BACKGROUND Polycystic ovary syndrome (PCOS) is a common gynecological disease characterized by chronic oligoanovulation, clinical/biochemical hyperandrogenism, polycystic ovaries, and insulin resistance. Accumulating evidence has shown that PCOS-related ovarian dysfunction is the main cause of anovulatory infertility. Clomiphene citrate (CC) is the first-line therapy for PCOS patients; however, approximately 15-40% PCOS patients are resistant to CC treatment. It has been demonstrated that PCOS is a chronic pro-inflammatory state, as some pro-inflammatory cytokines were elevated in the peripheral circulation of PCOS patients, but whether altered inflammatory cytokines expression in PCOS patients is associated with blunted response to CC remains unknown. MATERIAL AND METHODS We recruited 44 CC-resistant PCOS patients, along with 55 age and body mass index (BMI)-matched CC-sensitive PCOS patients. Ovulation was induced by administrating 50-100 mg/day CC on days 5 to 9 of each menstrual cycle. The cytokine profiles were detected by cytokine antibody microarrays and further validated by ELISAs. RESULTS CC-resistant patients had higher levels of high-sensitivity C-reactive protein (hsCRP) than the CC-sensitive individuals. A growth factor, angiopoietin-2, was significantly reduced [1.64 (0.93-1.95) vs. 1.08 (0.85-1.34), p<0.05], while a chemokine CXCL-16 was significantly increased (9.10±2.35 vs. 10.41±2.82, p<0.05) in CC-resistant patients compared to the CC-sensitive subjects. CXCL-16 was positively correlated with hsCRP (r=0.33, p<0.01). Logistic regression analysis showed that angiopoietin-2 and CXCL-16 are associated with CC resistance. CONCLUSIONS Circulating cytokines are disturbed in CC-resistant PCOS patients. Altered angiopoietin-2 and CXCL-16 levels might compromise the responsiveness of the ovary to CC through up-regulating angiogenesis and inflammation.

Prevalence and Sociodemographic and Lifestyle Determinants of Anemia during Pregnancy: A Cross-Sectional Study of Pregnant Women in China.

OBJECTIVE: This study aimed to assess the differences regarding anemia among pregnant women with diverse characteristics and lifestyle factors. METHODS: A cross-sectional study of pregnant women was conducted between June and August 2015 in 16 hospitals in five provinces of Mainland China. Self-reported doctor-diagnosed anemia was used in the study. RESULTS: We included 2345 pregnant women. Of the participants, 1755 (74.8%) were pregnant women of first pregnancy (PWFP) and 590 (25.2%) were second pregnancy (PWSP). The mean age of the participants was 28.1 years (SD 4.1). Overall, the prevalence of anemia was 12.7% (13.4% and 10.7% among PWFP and PWSP, respectively). The prevalence for not eating breakfast was 11.0%. Compared with PWFP, PWSP was inversely associated with the risk of anemia (odds ratio (OR) 0.66, 95% CI 0.48-0.91). Compared with those being registered in a low ranking hospital, pregnant women who were admitted to a high (OR 0.40, 95% CI 0.28-0.57) or a medium ranking hospital (OR 0.58, 95% CI 0.37-0.92) were inversely associated with the risk of anemia. Compared with women of low income (<¥4,500), those with high income were less likely to have anemia (OR 0.68, 95% CI 0.50-0.94). Compared with women with non-manual jobs, women with manual jobs (OR 1.70, 95% CI 1.17-2.45) and unemployed women (OR 1.42, 95% CI 1.04-1.93) were associated with a greater likelihood of suffering from anemia. CONCLUSIONS: Pregnant women not eating breakfast are of concern. Anemia is highly prevalent among pregnant women in China. Lower socio-economic status, manual jobs, PWFP, and those who attend a lower quality hospital have a greater likelihood of suffering from anemia. Tailored interventions are needed to address these issues.

MicroRNA-764-3p regulates 17ß-estradiol synthesis of mouse ovarian granulosa cells by targeting steroidogenic factor-1.

Previous studies have reported that microRNA-764-3p (miR-764-3p) is one of the most up-regulated microRNAs (miRNAs) in TGF-ß1-stimulated mouse ovarian granulosa cells. However, little is known about the roles and mechanisms of miR-764-3p in granulosa cell function during follicular development. In this study, we found that overexpression of miR-764-3p inhibited 17ß-estradiol (E2) synthesis of granulosa cells through directly targeting steroidogenic factor-1 (SF-1). MiR-764-3p inhibited SF-1 by affecting its messenger RNA (mRNA) stability, which subsequently suppressed the expression levels of Cyp19a1 gene (aromatase, a downstream target of SF-1). In addition, SF-1 was involved in regulation of miR-764-3p-mediated Cyp19a1 expression in granulosa cells which contributed, at least partially, to the effects of miR-764-3p on granulosa cell E2 release. These results suggest that miR-764-3p functions to decrease steroidogenesis by targeting SF-1, at least in part, through inactivation of Cyp19a1. Taken together, our data provide mechanistic insights into the roles of miR-764-3p on E2 synthesis. Understanding of potential miRNAs affecting estrogen synthesis will help to diagnose and treat steroid-related diseases.

Association between Breastfeeding and Endometrial Cancer Risk: Evidence from a Systematic Review and Meta-Analysis.

Quantification of the association between breastfeeding and risk of endometrial cancer is still conflicting. We therefore conducted a meta-analysis to assess the association between breastfeeding and endometrial cancer risk. Pertinent studies were identified by a search of PubMed and Web of Knowledge through April 2015. A random effect model was used to combine the data for analysis. Sensitivity analysis and publication bias were conducted. Dose-response relationships were assessed by restricted cubic spline and variance-weighted least squares regression analysis. Fourteen articles involving 5158 endometrial cancer cases and 706,946 participants were included in this meta-analysis. Pooled results suggested that breastfeeding significantly reduced the risk of endometrial cancer (summary relative risk (RR): 0.77, 95% CI: 0.62-0.96, I2: 63.0%), especially in North America (summary RR: 0.87, 95% CI: 0.79-0.95). A linear dose-response relationship was found, with the risk of endometrial cancer decreased by 2% for every one-month increase in the duration of breastfeeding (summary RR: 0.98, 95% CI: 0.97-0.99). Our analysis suggested that breastfeeding, particularly a longer duration of breastfeeding, was inversely associated with the risk of endometrial cancer, especially in North America, but not in Europe and Asia, probably due to the small number of cases included. Due to this limitation, further studies originating in other countries are required to assess the association between breastfeeding and endometrial cancer risk.

Involvement of phospholipases C and D in the defence responses of riboflavin-treated tobacco cells.

Riboflavin is an activator of defence responses in plants that increases resistance against diseases caused by fungal, oomycete, bacterial and viral pathogens. However, the mechanisms driving defence activation by riboflavin are poorly understood. We investigated the signal transduction pathways of phospholipase C (PLC) and phospholipase D (PLD) in tobacco (Nicotiana tabacum) suspension cells using a pharmacological approach to confirm whether riboflavin-mediated activation of the defence response is dependent on both PLC and PLD. The expression patterns analysed by quantitative reverse transcription-polymerase chain reaction demonstrated that the tobacco PLC and PLD gene families were differentially expressed in riboflavin-treated tobacco cells. PLC and PLD expression accompanied defence responses including the expression of defence response genes (PAL, PR-1a and PR-1b), the production of hydrogen peroxide and the accumulation of the phytoalexin scopoletin in tobacco cells treated with riboflavin. These defence responses were significantly inhibited in the presence of the PLC inhibitor U73122 and the PLD inhibitor 1-butanol; however, inhibitor analogues had no effect. Moreover, treating tobacco cells with phosphatidic acid, a signalling molecule produced by phospholipase catalysis, induced the accumulation of the phytoalexin scopoletin and compensated for the suppressive effects of U73122 and 1-butanol on riboflavin-induced accumulation of the phytoalexin. These results offer pharmacological evidence that PLC and PLD play a role in riboflavin-induced defences of tobacco.