Programmed cell death in autoimmune diseases: ferroptosis.

Ferroptosis is an iron dependent cell death driven by lipid peroxidation. Over the past decade, increasing evidence has confirmed that ferroptosis plays an irreplaceable role in the occurrence and development of many diseases, including various cancers, neurodegenerative diseases, cardiovascular diseases and autoimmune diseases. Autoimmune disease is an inflammatory disease characterized by the breakdown of immune tolerance. Nowadays, accumulating evidence indicates that ferroptosis is closely related to the pathogenesis of autoimmune diseases. Therefore, this review briefly introduced the mechanism of ferroptosis, and focused on the related research of ferroptosis in multiple autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), ankylosing spondylitis (AS). In addition, we also presented the idea of targeting ferroptosis as a potential therapeutic target for patients with autoimmune diseases, which may provide a direction for the development of new therapeutic strategies.

Hollow-Channel Paper Analytical Devices Supported Biofuel Cell-Based Self-Powered Molecularly Imprinted Polymer Sensor for Pesticide Detection.

Herein, a paper-based glucose/air biofuel cell (BFC) was constructed and implemented for self-powered pesticide detection. Our developed paper-based chip relies on a hollow-channel to transport fluids rather than capillarity, which reduces analysis times as well as physical absorption. The gold nanoparticles (Au NPs) and carbon nanotubes (CNTs) were adapted to modify the paper fibers to fabricate the flexible conductive paper anode/cathode electrode (Au-PAE/CNT-PCE). Molecularly imprinted polymers (MIPs) using 2,4-dichlorophenoxyacetic acid (2,4-D) as a template were synthesized on Au-PAE for signal control. In the cathode, bilirubin oxidase (BOD) was used for the oxygen reduction reaction. Based on a competitive reaction between 2,4-D and glucose-oxidase-labeled 2,4-D (GOx-2,4-D), the amount of GOx immobilized on the bioanode can be simply tailored, thus a signal-off self-powered sensing platform was achieved for 2,4-D determination. Meanwhile, the coupling of the paper supercapacitor (PS) with the paper-based chip provides a simple route for signal amplification. Combined with a portable digital multi-meter detector, the amplified signal can be sensitively readout. Through rational design of the paper analytical device, the combination of BFC and PS provides a new prototype for constructing a low-cost, simple, portable, and sensitive self-powered biosensor lab-on-paper, which could be easily expanded in the field of clinical analysis and drug delivery.

Ningmitai capsule promotes calculi expulsion after RIRS for 10-20-mm upper urinary stones: a multicenter, prospective, randomized controlled trial.

To evaluate the efficacy and safety of the use of Ningmitai capsule as an adjunctive stone expulsion therapy after RIRS. All patients were diagnosed with upper urinary tract calculi measuring 10-20 mm. The patients who successfully underwent RIRS were randomly assigned to the NMT capsule group (Ningmitai capsule, 1.52 g, three times daily) or the control group for 4 weeks based on the random number table method. The primary endpoints were the stone expulsion rate (SER) and stone-free rate (SFR). The average stone expulsion time (SET), average stone-free time (SFT) and complications were recorded. Between July 2, 2019, and December 17, 2020, 220 participants successfully underwent RIRS across 6 centers; 123 of them were randomized according to the exclusion criteria, and 102 (83%) were included in the primary analysis. The SERs on the 3rd, 7th, 14th and 28th days were significantly increased in the NMT capsule group compared with the control group (78.95% vs. 31.11%, 92.98% vs. 55.56%, 94.74% vs. 64.44%, 100% vs. 82.22%, respectively, p < 0.05). The SFRs on the 3rd and 7th days were not different (p > 0.05), while those on the 14th and 28th days were higher in the NMT capsule group (63.16% vs. 24.44% and 92.98% vs. 68.89%, p < 0.05). The average SET and average SFT of the NMT capsule group were remarkably shorter than those of the control group (p < 0.001). During the follow-up period, there were no significant differences in urine RBC counts between the two groups (p > 0.05). The urine WBC counts of the NMT capsule group were significantly lower than those of the control group on the 14th day (p = 0.011), but there was no difference on the 3rd, 7th or 28th day (p > 0.05). The analgesic aggregate of the NMT capsule group was also much lower (p = 0.037). There were no significant differences in adverse events (p > 0.05), and they improved significantly without sequelae. This study indicated that NMT capsules can significantly promote stone clearance and are more effective and safer for upper urinary calculi after RIRS.Trial registration Chinese Clinical Trial Registration No. ChiCTR1900024151.Date of registration June 28, 2019.

Appendiceal Onlay Flap Ureteroplasty for the Treatment of Complex Ureteral Strictures: Initial Experience of Nine Patients.

Purpose: To evaluate the onlay technique using the appendix for ureteral reconstruction and describe the initial experience of nine operations performed by one surgeon. Methods: Nine patients with complex ureteral strictures who underwent appendiceal onlay flap ureteroplasty since May 2019 were recruited from our RECUTTER database. There were seven men and two women, with a mean age of 38.9 years; four patients underwent robot-assisted laparoscopic surgery, and five patients underwent traditional laparoscopic surgery. All patients had iatrogenic injuries of the ureter after treatment of stone disease. Seven patients had proximal ureteral strictures, and two had midureteral strictures. The mean stricture length of the nine patients was 3.9 (range 3-4.5) cm. Nephrostomy was performed in seven patients before they presented to our center, and the other two patients had indwelling Double-J ureteral stents. Results: All nine operations were effectively completed without open conversion. The mean operation time was 182 (range 135-220) minutes, the mean estimated blood loss was 71 (range 20-100) mL, and the mean length of postoperative hospital stay was 9 (range 6-12) days. No postoperative complications of high grade (Clavien-Dindo III and IV) occurred within 30 days of surgery. All the patients had their Double-J ureteral stents and nephrostomy tubes removed after complete ureteroscopy and upper urinary tract urodynamic examination or CTU, which showed that the anastomosis healed well and that the urinary tract was unobstructed, respectively. The objective success rate was 100% (all the patients had endoscopic and radiographic resolution of their ureteral strictures). The subjective success rate was 88.9% (one patient developed recurrent back discomfort and a 0.5 cm calculus was found in her renal pelvis). Conclusions: Appendiceal onlay flap ureteroplasty is a viable and effective technique for treating complex proximal and middle ureteral strictures at the right side.

Knockdown of lncRNA CCAT1 enhances sensitivity of paclitaxel in prostate cancer via regulating miR-24-3p and FSCN1.

Drug resistance limits the efficacy of chemotherapy in human cancers. Previous studies reported that long noncoding RNA colon cancer-associated transcript 1 (CCAT1) regulated progression of prostate cancer (PCa). However, the potential role of CCAT1 in the sensitivity of paclitaxel (PTX) in PCa and its mechanism remain largely unknown. The PTX-resistant PCa cells were established in PC3 and DU145 cells by increasing concentrations of PTX. The expressions of CCAT1, microRNA-24-3p (miR-24-3p) and fascin1 (FSCN1) were measured by quantitative real-time polymerase chain reaction. The viability and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry and western blot, respectively. The interaction among CCAT1, miR-24-3p and FSCN1 was explored by luciferase activity, RNA immunoprecipitation, RNA pull-down and western blot, respectively. Results showed that the expressions of CCAT1 were up-regulated and miR-24-3p was down-regulated in PCa and PTX-resistant PCa cells (PC3-TXR and DU145-TXR). Knockdown of CCAT1 or overexpression of miR-24-3p inhibited survival rate, half maximal inhibitory concentration (IC50) of PTX but increased apoptosis in PC3-TXR and DU145-TXR cells after treatment of PTX. miR-24-3p was bound to CCAT1 and its abrogation reversed knockdown of CCAT1-mediated increase of PTX sensitivity in PC3-TXR and DU145-TXR cells. Moreover, FSCN1 restoration attenuated miR-24-3p-mediated inhibition of PTX resistance. Besides, FSCN1 level was enhanced in PCa and PTX-resistant PCa cells and regulated by CCAT1 and miR-24-3p. Our data suggested interference of CCAT1 contributed to PTX sensitivity in PCa by regulating miR-24-3p and FSCN1, indicating a novel avenue for treatment of PCa through regulating chemoresistance.

MALAT1 knockdown inhibits prostate cancer progression by regulating miR-140/BIRC6 axis.

BACKGROUND: Prostate cancer (PCa) is the second most common cancer among men globally. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to be implicated in tumorigenesis and progression of PCa. However, the pathogenesis of MALAT1 in PCa has not been thoroughly elaborated. METHODS: RT-qPCR assay was conducted to measure expression of MALAT1, microRNA-140 (miR-140) and Baculoviral IAP repeat containing 6 (BIRC6) mRNA. Protein expression of BIRC6 was detected by western blot assay. Cell proliferative ability was assessed by MTS and Edu retention assays. Cell migratory and invasive abilities were evaluated by wound healing assay and Transwell invasion assay, respectively. Cell apoptotic rate was examined using a flow cytometry. The interaction between miR-140 and MALAT1 or BIRC6 3'UTR was explored by luciferase, RNA immunoprecipitation (RIP) and RNA pull down assays. Xenograft models of PCa were established to further explore the role and molecular mechanism of MALAT in PCa tumorigenesis in vivo. RESULTS: MALAT1 and BIRC6 were highly expressed in human PCa tumor tissues and cell lines. MALAT1 or BIRC6 knockdown inhibited cell proliferation, migration and invasion and induced cell apoptosis in PCa. MiR-140 could directly bind with MALAT1 or BIRC6 3'UTR. Moreover, MALAT1 knockdown inhibited BIRC mRNA and protein expression through upregulating miR-140 in PCa cells. Additionally, MALAT1 knockdown inhibited PCa xenograft tumor growth by regulating miR-140/BIRC6 axis in vivo. CONCLUSION: MALAT1 knockdown hindered PCa progression by regulating miR-140/BIRC6 axis in vitro and in vivo, hinting the potential value of MALAT1 in the management of PCa.

ß3 adrenergic receptor antagonist SR59230A exerts beneficial effects on right ventricular performance in monocrotaline-induced pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease with a high mortality rate. Previous studies have revealed the important function of the ß3 adrenergic receptor (ß3-AR) in cardiovascular diseases, and the potential beneficial effects of numerous ß3-AR agonists on pulmonary vasodilation. Conversely, a number of studies have proposed that the antagonism of ß3-AR may prevent heart failure. The present study aimed to investigate the functional involvement of ß3-AR and the effects of the ß3-AR antagonist, SR59230A, in PAH and subsequent heart failure. A rat PAH model was established by the subcutaneous injection of monocrotaline (MCT), and the rats were randomly assigned to groups receiving four weeks of SR59230A treatment or the vehicle control. SR59230A treatment significantly improved right ventricular function in PAH in vivo compared with the vehicle control (P<0.001). Additionally, the expression level of ß3-AR was significantly upregulated in the lung and heart tissues of PAH rats compared with the sham group (P<0.01), and SR59230A treatment inhibited this increase in the lung (P<0.05), but not the heart. Specifically, SR59230A suppressed the elevated expression of endothelial nitric oxide and alleviated inflammatory infiltration to the lung under PAH conditions. These results are, to the best of our knowledge, the first to reveal that SR59230A exerts beneficial effects on right ventricular performance in rats with MCT-induced PAH. Furthermore, blocking ß3-AR with SR59230A may alleviate the structural changes and inflammatory infiltration to the lung as a result of reduced oxidative stress.

Robust Trajectory Tracking Control for Variable Stiffness Actuators With Model Perturbations.

Variable Stiffness Actuators (VSAs) have been introduced to develop new-generation compliant robots. However, the control of VSAs is still challenging because of model perturbations such as parametric uncertainties and external disturbances. This paper proposed a non-linear disturbance observer (NDOB)-based composite control approach to control both stiffness and position of VSAs under model perturbations. Compared with existing non-linear control approaches for VSAs, the distinctive features of the proposed approach include: (1) A novel modeling method is applied to analysis the VSA dynamics under complex perturbations produced by parameter uncertainties, external disturbances, and flexible deflection; (2) A novel composite controller integrated feedback linearization with NDOB is developed to increase tracking accuracy and robustness against uncertainties. Both simulations and experiments have verified the effectiveness of the proposed method on VSAs.

Long noncoding RNA GAS5 modulates α-Solanine-induced radiosensitivity by negatively regulating miR-18a in human prostate cancer cells.

Radiotherapy is an adjuvant treatment of surgery in prostate cancer, while radioresistance has been the challenge of treatment. It has been reported that α-Solanine exhibits anti-cancer activity and enhances the chemo- and radio-sensitivity in several human cancers, whereas the role of α-Solanine on radiosensitivity to PCa remains to be uncovered yet. We found α-Solanine decreased cell viability in human PCa cells rather than normal prostate epithelial cells in vitro. Functional experiments showed that cell viability and colonies formation were declined & apoptosis rate and DNA double strand breaks (DSBs) marker γ-H2AX expressions were elevated by α-Solanine in PCa cells treated with X-ray irradiation, compared with X-ray irradiation treatment only. GAS5 was down-regulated & miR-18a was up-regulated in PCa cells, which was reversed in the presence of α-Solanine. Effects of ectopic GAS5 on inhibiting cell viability and survival & promoting apoptosis and DNA damage were reversed by miR-18a overexpression in PCa cells. Moreover, GAS5 regulated miR-18a expression by target binding during α-Solanine treatment. Collectively, α-Solanine suppresses cell proliferation and promotes radiosensitivity through up-regulating GAS5/miR-18a pathway in PCa. Our results provide a novel mechanism of α-Solanine treatment in human prostate cancer and help to develop a new approach to sensitizing radioresistant prostate cancer cells by targeting GAS5/miR-18a.

Exposure to Pb and Cd alters MCT4/CD147 expression and MCT4/CD147-dependent lactate transport in mice Sertoli cells cultured in vitro.

Sertoli cells (SCs) provide lactate as an energy substrate to develop germ cells during spermatogenesis. Lead (Pb) and cadmium (Cd) can induce SC toxicity. However, the mechanisms remain unclear. This study aimed to investigate the molecular mechanisms by which Pb and Cd alter lactate transport and production by SCs. Mouse SC line (15P-1 cells) were cultured in the absence and presence of lead acetate (PbAc, 1, 10, 20 and 30 µM) or cadmium chloride (CdCl2, 0.5, 5, 10 and 15 µM) for 24 h. The results showed that PbAc exposure significantly decreased lactate dehydrogenase (LDH) activity and mRNA level, intracellular and extracellular lactate, and MCT4 and CD147 protein levels but increased MCT4 and CD147 mRNA levels. However, PbAc did not alter the glucose uptake, glucose transporters 1 (GLUT1) and 3 (GLUT3) mRNA expression of SCs. Thus, PbAc mainly decreased lactate production by inhibiting LDH activity. In CdCl2-treated SCs, intracellular lactate content increased but extracellular lactate content decreased significantly, P < .05. The glucose uptake, LDH activity, and mRNA expression of GLUT1, GLUT3 and LDH, all significantly increased. But the mRNA and protein levels of MCT4 and CD147 significantly decreased. Moreover, the fluorescence intensity of co-localizations of the MCT4-CD147 complex dose-dependently decreased in the cell membrane. Thus, CdCl2 may reduce lactate export by suppressing MCT4 and CD147 expression. These results suggest that PbAc and CdCl2 disrupt lactate production and transport in mouse SCs by disturbing glycolysis or inhibiting MCT4-CD147 transporter expression and co-localizations.

Dietary Intakes of Calcium, Iron, Magnesium, and Potassium Elements and the Risk of Colorectal Cancer: a Meta-Analysis.

The purpose of this study was to analyze the existing studies and to investigate the relationship between the risk of colorectal cancer (CRC) and intakes of four individual dietary elements calcium (Ca), iron (Fe), magnesium (Mg), and potassium (K). All relevant articles in both Chinese and English were searched and collected from PubMed, Web of Science, and Chinese National Knowledge Infrastructure databases up to December 17, 2017. There were 29 eligible literatures selected for further meta-analysis, including 14 cohort studies and 15 case-control studies. The meta-analysis of cohort studies indicated that the high intakes of dietary Ca and Mg were negatively associated with the risk of CRC, as the hazard ratios (HR) were 0.76 (95% confidence interval (CI) 0.72, 0.80) and 0.80 (95% CI 0.73, 0.87), respectively. Nevertheless, high intake of dietary heme Fe was positively correlated to the incidence of colon cancer (HR = 1.01, 95% CI 0.82, 1.19) and rectal cancer (HR = 1.04, 95% CI 0.67, 1.42). A meta-analysis of case-control studies indicated that high intakes of dietary Ca, Mg, and K were negatively related with the occurrence of CRC, because the odds ratios (OR) were 0.36 (95% CI 0.32, 0.40), 0.80 (95% CI 0.63, 0.98) and 0.97 (95% CI 0.74, 1.21), respectively. However, high Fe intake from diet was positively correlated with the rising increasing of CRC (OR = 1.04, 95% CI 0.91, 1.18). More research is needed to indicate the risk relationship between element intake and CRC.

MiR-145-modulated SOX9-mediated hypospadias through acting on mitogen-activated protein kinase signaling pathway.

This study primarily explored how miR-145, mitogen-activated protein kinase (MAPK) signaling and a downstream transcription factor (i.e., SOX9) mediated development of hypospadias. The hypospadias tissues and preputial tissues were isolated from pediatric inpatients postoperatively. Simultaneously, the rat models of hypospadias were established, and spermatogonial stem cells were separated. The expressions of proteins that symbolized cell apoptosis and oxidative stress were quantified via western blot analysis. Furthermore, the apoptosis, proliferation, and viability of cells were evaluated by means of flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. The results of microarray indicated miR-145 as a differentially expressed biomarker between hypospadias tissues and normal tissues (p < 0.05). Moreover, rat models of hypospadias were observed with markedly lower vitamins A and E levels, reduced expressions of proteins relevant to oxidative stress (i.e., Nrf2, HO-1, Gpx, and SOD-1), as well as enhanced Bax and cleaved caspase-3 expressions ( p < 0.05). Furthermore, SOX9 was found to be targeted by miR-145, and it was also modified by phosphorylated extracellular-regulated kinase (p-ERK), a portion of MAPK signaling ( p < 0.05). The p-ERK was significantly regulated after altering the expression of miR-145 ( p < 0.05). Moreover, activation of p-ERK and transfection of pcDNA-SOX9 could cause higher expression of apoptins and larger apoptotic proportion of cells ( p < 0.05), yet transfection of miR-145 mimic led to improved cell apoptosis and depressed cell viability ( p < 0.05). In conclusion, SOX9, which was regulated by both miR-145 and miR-145/MAPK signaling, could be involved in the pathogenesis of hypospadias.

Identification of drug repurposing candidates based on a miRNA-mediated drug and pathway network for cardiac hypertrophy and acute myocardial infarction.

BACKGROUND: Cardiac hypertrophy and acute myocardial infarction (AMI) are two common heart diseases worldwide. However, research is needed into the exact pathogenesis and effective treatment strategies for these diseases. Recently, microRNAs (miRNAs) have been suggested to regulate the pathological pathways of heart disease, indicating a potential role in novel treatments. RESULTS: In our study, we constructed a miRNA-gene-drug network and analyzed its topological features. We also identified some significantly dysregulated miRNA-gene-drug triplets (MGDTs) in cardiac hypertrophy and AMI using a computational method. Then, we characterized the activity score profile features for MGDTs in cardiac hypertrophy and AMI. The functional analyses suggested that the genes in the network held special functions. We extracted an insulin-like growth factor 1 receptor-related subnetwork in cardiac hypertrophy and a vascular endothelial growth factor A-related subnetwork in AMI. Finally, we considered insulin-like growth factor 1 receptor and vascular endothelial growth factor A as two candidate drug targets by utilizing the cardiac hypertrophy and AMI pathways. CONCLUSION: These results provide novel insights into the mechanisms and treatment of cardiac hypertrophy and AMI.

Research Trends and Hotspots Analysis Related to the Effects of Xenobiotics on Glucose Metabolism in Male Testes.

This study aimed to integrate and analyze the existing studies and to explore research trends and hotspots related to the effects of xenobiotics on glucose metabolism in male testes. All articles were retrieved from the PubMed database, from an inception date up to 10 June 2017. CiteSpace software (version 5.1.R8 SE) was used for the co-word cluster analysis. A total of 165 eligible publications were included in this study. In 1949⁻1959, only two articles were published. After 1960, the number of articles increased steadily. These articles were published in 97 journals, in particular, in the Indian Journal of Experimental Biology (11 articles, 6.7%). Most of the authors (87.0%) only published one article. Only a few established research teams, mostly from the USA, worked consistently in this field. The main xenobiotics that had been studied were medicine and common environmental pollutants, e.g., gossypol, cadmium, di-n-butyl phthalate, and alpha-chlorohydrin. The hotspot keywords were Sertoli cell, lactate dehydrogenase, 6-phosphate dehydrogenase, oxidative stress, and glucose metabolism. The focus of research had been changed overtime. This is the first bibliometric study between xenobiotics and glucose metabolism in the male testes. The findings suggest that environmental pollutants have become a huge concern, and related research should be strengthened.

[Overexpression of miR-519d-3p inhibits the proliferation of DU-145 prostate cancer cells by reducing TRAF4].

Objective To observe the effect of microRNA-519d-3p (miR-519d-3p) on the proliferation of prostate cancer cells and explore the possible molecular mechanism. Methods The expression level of miR-519d-3p in PC-3, DU-145, 22RV1, PC-3M, LNCaP human prostate cancer cells and RWPE-1 human normal prostate epithelial cells was detected by real-time quantitative PCR. miR-519d-3p mimics or negative control microRNAs (miR-NC) was transfected into the prostate cancer cells with the lowest level of miR-519d-3p expression. Transfection efficiency was examined. The effect of miR-519d-3p on the cell cycle of prostate cancer was detected by flow cytometry. MTT assay and plate clone formation assay were used to detect its effect on the proliferation of prostate cancer cells. Bioinformatics software was used to predict and dual luciferase reporter assay was used to validate the target gene of miR-519d-3p. Real-time quantitative PCR was used to detect the expression of miR-519d-3p target gene. Western blot analysis was used to detect the expression of target gene protein and downstream protein. Results The expression of miR-519d-3p in normal prostate epithelial cells was significantly higher than that in prostate cancer cells, and the lowest was found in DU-145 cells. After transfected with miR-519d-3p mimics, the expression level of miR-519d-3p in DU-145 cells increased significantly. Bioinformatics prediction and dual luciferase reporter gene confirmed that tumor necrosis factor receptor associated factor 4 (TRAF4) was the target gene of miR-519d-3p. Overexpression of miR-519d-3p significantly reduced the expression of TRAF4 gene and its downstream TGF-ß signaling pathway proteins in the prostate cancer cells. Conclusion The expression of miR-519d-3p is down-regulated in prostate cancer cells. Overexpression of miR-519d-3p can inhibit the proliferation of prostate cancer cells. The possible mechanism is that miR-519d-3p inhibits the expression of TRAF4.

The Relationship of Children's Intelligence Quotient and Blood Lead and Zinc Levels: a Meta-analysis and System Review.

The purpose of this study was to analyze the existing studies and to investigate the relationship between children's full-scale intelligence quotient (FIQ), verbal IQ (VIQ), and performance IQ (PIQ) and their blood lead (Pb) and zinc (Zn) levels. All documents in Chinese and English were collected from the PubMed, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) databases from inception date to December 30, 2016. RevMan software (version 5.2) was used for the meta-analysis and Stata software (version 12.0) for the meta-regression and sensitivity analyses. A total of 32 eligible literatures was included in the study. Seven prevalence studies showed that the blood Pb level was negatively correlated with children's IQ. The results of the meta-analysis from 22 case-control studies indicate a significant difference between FIQ and PIQ with blood Pb levels, detailed as the FIQ score with a weighted mean difference (WMD) = -6.60 (95% CI: -9.01, -4.20), P < 0.001; PIQ WMD = -8.85 (95% CI: -12.651, -5.05), P < 0.001; but VIQ WMD = -3.32 (95% CI: -6.98, 0.33), P > 0.05. Three studies on the blood Zn concentrations were with a FIQ WMD = 7.88 (95% CI: -0.07, 15.83), VIQ WMD = 7.73 (95% CI: -7.40, 22.86), and PIQ WMD = 6.69 (95% CI: -7.13, 20.51), all P > 0.05. The results indicate that Pb is harmful to children's intelligence development, especially in PIQ. Zn is beneficial to intelligence, although more studies are needed.

[miR-503-5p inhibits the proliferation of T24 and EJ bladder cancer cells by interfering with the Rb/E2F signaling pathway].

Objective To observe the effect of microRNA-503-5p (miR-503-5p) on the growth of T24 and EJ bladder cancer cells, and explore the possible molecular mechanism. Methods The miR-504-5p mimics or miR-NC was transfected into T24 and EJ cells. The target gene of miR-503-5p was predicted by bioinformatics. The expressions of E2F transcription factor 3 (E2F3) mRNA and Rb/E2F signaling pathway mRNA were detected by the real-time quantitative PCR (qPCR). The expressions of Rb/E2F signal pathway proteins E2F3, cyclin E, CDK2, Rb and p-Rb were detected by Western blotting. The cell cycle of bladder cancer cell lines was determined by flow cytometry. MTT assay and plate cloning assay were performed to observe the proliferation ability of bladder cancer cells. Results After miR-503-5p mimics transfection, the expression of miR-503-5p in bladder cancer cells significantly increased. The increased expression of miR-503-5p significantly reduced the expressions of E2F3 mRNA and Rb/E2F signaling pathway mRNA in bladder cancer cells. What's more, the expressions of Rb/E2F signal pathway proteins were down-regulated. The bladder cancer cells were arrested in G0/G1 phase, and their growth was significantly inhibited by miR-503-5p. Conclusion The miR-503-5p over-expression can inhibit the growth of bladder cancer cell lines T24 and EJ by down-regulating the expression of the Rb/E2F signaling pathway.

Different exposure levels of fine particulate matter and preterm birth: a meta-analysis based on cohort studies.

The previous studies estimated the association between PM2.5 (particulate matter with aerodynamic diameter less than or equal to 2.5 µm) exposure during pregnancy and preterm birth, only considered and highlighted the hazard effects of high levels of air pollutant exposure, and underestimated that low levels of pollutant exposure might also affect pregnancy outcome. We conducted a meta-analysis of 11 cohort studies, a total of more than 1,500,000 subjects. The results of these studies were pooled by exposure levels and study periods. PM2.5 exposure during pregnancy was positively associated with preterm birth (OR = 1.15, 95% CI = 1.07-1.23), and during the first trimester of pregnancy, low levels of PM2.5 exposure were also positively associated with preterm birth (OR = 1.17, 95% CI = 1.04-1.30). It is important to protect pregnant women from PM2.5 exposures, especially during their first trimester of pregnancy even when the ambient PM2.5 concentration is relatively low. More relevant health policy should be carried out to prevent hazard effect of air pollutants.

Protective Effects of PGC-1α Against Lead-Induced Oxidative Stress and Energy Metabolism Dysfunction in Testis Sertoli Cells.

The reproductive system is sensitive to lead (Pb) toxicity, which has long been an area of research interest, but the underlying mechanisms remain to be illustrated. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is pivotal in mitochondrial function. In this study, mouse testis Sertoli cells (TM4 cells), PGC-1α lower-expression (PGC-1α(-)) TM4 cells and PGC-1α overexpression (PGC-1α(+)) TM4 cells were used to explore the protective roles of PGC-1α against lead toxicity on the mouse reproductive system. Lead acetate (PbAc) exposure decreased the expression level of PGC-1α, increased the intracellular level of reactive oxygen species (ROS), and reduced the level of ATP in the three TM4 cell lines. The effects of PbAc on intracellular ATP level and on ROS content were significantly weakened in PGC-1α(+)TM4 cells versus TM4 cells and were significantly amplified in PGC-1α(-)TM4 cells versus TM4 cells. These results suggest that PGC-1α is a protective factor against PbAc-induced oxidative stress and energy metabolism dysfunction in the mouse reproductive system, thereby holding the potential of being developed as a preventive or therapeutic strategy against disorders induced by lead exposure.