Pooled-analysis of tadalafil and tamsulosin for ureteral calculi.

Objective: Urolithiasis is a common urological diseases and affects the daily life of patients. Medical expulsive therapy has become acceptable for many parents. We conducted a meta-analysis to determine the efficacy and safety of tadalafil compared with tamsulosin for treating distal ureteral stones less than 10 mm in length. Methods: Related studies were identified via searches of the PubMed, Embase, and Cochrane Library databases. All the articles that described the use of tadalafil and tamsulosin for treating distal ureteral stones were collected. Results: A total of 14 studies were included in our meta-analysis. Our results revealed that tadalafil enhanced expulsion rate [odds ratio (OR) = 0.68, 95% confidence interval (CI): 0.47 to 0.98, p = 0.04]; reduced expulsion time [mean difference (MD) = 1.22, 95% CI (0.13, 2.30), p = 0.03]; lowered analgesia use [MD = 38.66, 95% CI (7.56, 69.77), p = 0.01] and hospital visits [MD = 0.14, 95% CI (0.06, 0.22), p = 0.0006]. According to our subgroup analysis, either tadalafil 5 mg or 10 mg did not promote expulsion rate and accelerate expulsion time compared with tamsulosin. But patients receiving 5 mg tadalafil decreased analgesia usage [MD = 101.04, 95% CI (67.56, 134.01), p < 0.00001]. Conclusion: Compared with tamsulosin, tadalafil demonstrates a higher expulsion rate and less expulsion time for patients with distal ureteral stones less than 10 mm with a favorable safety profile.

Comparison of the efficacy and complications of tolterodine and α-adrenergic receptor blockers in improving ureteral stent-related symptoms: A systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic evaluation of the therapeutic efficacy and complications of tolterodine and α-adrenergic receptor blockers in alleviating ureteral stent-related symptoms. METHODS: Until August 2023, we conducted a comprehensive literature search on PubMed, Embase, Web of Science, and Cochrane Library to identify randomized controlled trials evaluating the efficacy and complications of tolterodine and α-adrenergic receptor blockers in treating ureteral stent-related symptoms. Two reviewers independently screened studies and extracted data. The scores from various domains of the Ureteral Stent Symptom Questionnaire (USSQ) were summarized and compared, and statistical analysis was performed using RevMan 5.4.0 software. RESULTS: A total of 8 studies met the inclusion criteria for our analysis. These studies were conducted at different centers. All studies were randomized controlled trials, involving a total of 487 patients, with 244 patients receiving α-adrenergic receptor blockers and 243 patients receiving tolterodine. The results showed that tolterodine demonstrated significantly better improvement in body pain (MD, 1.56; 95% CI [0.46, 2.66]; p = 0.005) (MD, 0.46; 95% CI [0.12, 0.80]; p = 0.008) (MD, 3.21; 95% CI [1.89, 4.52]; p = 0.00001) among patients after ureteral stent placement compared to α-adrenergic receptor blockers at different time points. Additionally, at 4 weeks, tolterodine showed superior improvement in general health (MD, 0.15; 95% CI [0.03, 0.27]; p = 0.01) and urinary symptoms (MD, 1.62; 95% CI [0.59, 2.66]; p = 0.002) compared to α-adrenergic receptor blockers, while at 6 weeks, tolterodine showed better improvement in work performance (MD, -1.60; 95% CI [-2.73, -0.48]; p = 0.005) compared to α-adrenergic receptor blockers. Additionally, the incidence of dry mouth (RR, 4.21; 95% CI [1.38, 12.87]; p = 0.01) is higher with the use of tolterodine compared to α-adrenergic receptor blockers. However, there were no significant statistical differences between the two drugs in other outcomes. CONCLUSION: This meta-analysis suggests that tolterodine is superior to α-adrenergic receptor blockers in improving physical pain symptoms after ureteral stent placement, while α-adrenergic receptor blockers are more effective than tolterodine in enhancing work performance. Additionally, the incidence of dry mouth is higher with the use of tolterodine compared to α-adrenergic receptor blockers. However, higher-quality randomized controlled trials are needed to further investigate this issue.

MaiJiTong granule attenuates atherosclerosis by reducing ferroptosis via activating STAT6-mediated inhibition of DMT1 and SOCS1/p53 pathways in LDLR-/- mice.

BACKGROUND AND PURPOSE: Atherosclerosis is the primary pathological basis of cardiovascular disease. Ferroptosis is a regulated form of cell death, a process of lipid peroxidation driven by iron, which can initiate and promote atherosclerosis. STAT6 is a signal transducer that shows a potential role in regulating ferroptosis, but, the exact role in ferroptosis during atherogenesis remains unclear. The Traditional Chinese Medicine Maijitong granule (MJT) is used for treating cardiovascular disease and shows a potential inhibitory effect on ferroptosis. However, the antiatherogenic effect and the underlying mechanism remain unclear. In this study, we determined the role of STAT6 in ferroptosis during atherogenesis, investigated the antiatherogenic effect of MJT, and determined whether its antiatherogenic effect was dependent on the inhibition of ferroptosis. METHODS: 8-week-old male LDLR-/- mice were fed a high-fat diet (HFD) at 1st and 10th week, respectively, to assess the preventive and therapeutic effects of MJT on atherosclerosis and ferroptosis. Simultaneously, the anti-ferroptotic effects and mechanism of MJT were determined by evaluating the expression of genes responsible for lipid peroxidation and iron metabolism. Subsequently, we reanalyzed microarray data in the GSE28117 obtained from cells after STAT6 knockdown or overexpression and analyzed the correlation between STAT6 and ferroptosis. Finally, the STAT6-/- mice were fed HFD and injected with AAV-PCSK9 to validate the role of STAT6 in ferroptosis during atherogenesis and revealed the antiatherogenic and anti-ferroptotic effect of MJT. RESULTS: MJT attenuated atherosclerosis by reducing plaque lesion area and enhancing plaque stability in both preventive and therapeutic groups. MJT reduced inflammation via suppressing inflammatory cytokines and inhibited foam cell formation by lowering the LDL level and promoting ABCA1/G1-mediated lipid efflux. MJT ameliorated the ferroptosis by reducing lipid peroxidation and iron dysregulation during atherogenesis. Mechanistically, STAT6 negatively regulated ferroptosis by transcriptionally suppressing SOCS1/p53 and DMT1 pathways. MJT suppressed the DMT1 and SOCS1/p53 via stimulating STAT6 phosphorylation. In addition, STAT6 knockout exacerbated atherosclerosis and ferroptosis, which abolished the antiatherogenic and anti-ferroptotic effects of MJT. CONCLUSION: STAT6 acts as a negative regulator of ferroptosis and atherosclerosis via transcriptionally suppressing DMT1 and SOCS1 expression and MJT attenuates atherosclerosis and ferroptosis by activating the STAT6-mediated inhibition of DMT1 and SOCS1/p53 pathways, which indicated that STAT6 acts a novel promising therapeutic target to ameliorate atherosclerosis by inhibiting ferroptosis and MJT can serve as a new therapy for atherosclerosis treatment.

Meta-analysis of perioperative outcomes and safety of percutaneous nephrostomy versus retrograde ureteral stenting in the treatment of acute obstructive upper urinary tract infection.

Background: The debate regarding the optimal drainage method for acute obstructive upper urinary tract infection persists, focusing on the choice between percutaneous nephrostomy (PCN) and retrograde ureteral stenting (RUS). Aims: This study aims to systematically examine the perioperative outcomes and safety associated with PCN and RUS in treating acute obstructive upper urinary tract infections. Methods: A comprehensive investigation was conducted using the Medline, Embase, Web of Science, and Cochrane databases up to December 2022, following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The utilized keywords included 'PCN', 'RUS', 'acute upper obstructive uropathy', and 'RCT'. Inclusion criteria encompassed studies providing accurate and analyzable data, which incorporated the total subject count, perioperative outcomes, and complication rates. The assessed perioperative outcomes included fluoroscopy time, normalization of temperature, normalization of serum creatinine, normalization of white blood cell (WBC) count, and operative time. Safety outcomes encompassed failure rate, intraoperative and postoperative hematuria, postoperative fever, postoperative pain, and postoperative nephrostomy tube or stent slippage rate. The study protocol was prospectively registered at PROSPERO (CRD42022352474). Results: The meta-analysis encompassed 7 trials involving 727 patients, with 412 assigned to the PCN group and 315 to the RUS group. The outcome of the meta-analysis unveiled a reduced occurrence of postoperative hematuria in the PCN group [odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.30-0.99, p = 0.04], along with a decreased frequency of insertion failure (OR = 0.42, 95% CI 0.21-0.81, p = 0.01). In addition, the RUS group exhibited a shorter fluoroscopy time than the PCN group (mean difference = 0.31, 95% CI 0.14-0.48, p = 0.0004). Conclusion: Given the significant impact of hematuria and catheterization failure on postoperative quality of life, the preference for PCN appears more advantageous than RUS.

Meta-analysis of perioperative outcomes and safety of percutaneous nephrostomy vs retrograde ureteral stenting in the treatment of acute obstructive upper urinary tract infection The optimal drainage method for acute obstructive upper urinary tract infection between PCN and RUS is currently debatable. Our meta-analysis found PCN performed better than RUS in hematuria and catheterization failure rate, although PCN was associated with longer exposure time.

A systematic review and meta-analysis of efficacy and safety comparing greenlight laser vaporization with transurethral resection of the prostate for benign prostatic hyperplasia with prostate volume less than 80 ml.

We conducted a meta-analysis to evaluate the efficacy and safety of photo selective vaporisation of the prostate (PVP) with the GreenLight Laser versus transurethral resection of the prostate (TURP) for the treatment of small-volume benign prostatic hyperplasia (BPH). As of July 2022, relevant literature in online databases such as Cochrane Library, PubMed, and Embase was searched, including studies published on or before that date, and there were 9 studies in total, including 5 RCTs and 4 non-RCTs. In total 1525 patients were included to compare the efficacy of PVP and TURP in treating BPH. The Cochrane Collaboration criteria were used to evaluate the risk of bias. The software was used for random effect meta-analysis with RevMan 5.3. Data extraction included: clinical baseline characteristics, perioperative parameters, complication rates, International Prostate Symptom Score (IPSS), prostate specific antigen (PSA), post-void residual urine (PVR), maximum flow rate (Qmax), and quality of life (QoL). The pooled analysis showed that PVP was associated with reduced blood loss, blood transfusion, clot retention, catheterization time, definitive catheter removal, and hospital stay, but was associated with longer operative time and more severe dysuria (all p < 0.05). The results of this meta-analysis show that PVP as a technique for the treatment of benign prostatic hyperplasia with a volume of less than 80 cc has similar efficacy to standard TURP in IPSS, PSA, PVR, Qmax and QoL, and is an effective alternative. It outperformed TURP in terms of blood transfusion, catheterization time and hospital stay, while TURP is superior to PVP in terms of operation time.

Wiskott-Aldrich syndrome gene as a prognostic biomarker correlated with immune infiltrates in clear cell renal cell carcinoma.

Introduction: The abnormal expression of the Wiskott-Aldrich syndrome protein (WASP) encoded by the Wiskott-Aldrich syndrome (WAS) gene has been implicated in tumor invasion and immune regulation. However, prognostic implications of WAS and its correlation tumor infiltrating in renal clear cell carcinoma (ccRCC) is not clear cut. Methods: The correlation between WAS expression, clinicopathological variables and clinical outcomes were evaluated using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Tumor Immune Estimation Resource (TIMER), UALCAN, Gene Expression Profiling Interaction Analysis (GEPIA), Kaplan-Meier (KM) plotter and other databases. Furthermore, we assessed the transcription expression of WAS in renal cancer tissues, various renal carcinoma cell lines and human renal tubular cells (HK2) using quantitative polymerase chain reaction (qPCR). A comprehensive analysis of multiple databases including TIMER, GEPIA, TISIDB, ESTIMATE algorithm, and CIBERSORT algorithm were performed to determine the correlation between WAS and tumor infiltrating immune cells in ccRCC. Results: The results displayed an increase in WAS mRNA level in ccRCC compared to normal tissue. WAS protein level was found highly expressed in cancer tissues, particularly within renal tumor cells via the human protein atlas (HPA). Interestingly, we found that elevated WAS expression was significantly positively correlated with the infiltration of CD8+ T cells, B cells, Monocytes, Neutrophils, Macrophages, T cell regulation, NK cells, and Dendritic cells in ccRCC. Bioinformatics demonstrated a strong correlation between WAS expression and 42 immune checkpoints, including the T cell exhaustion gene PD-1, which is critical for exploring immunotherapy for ccRCC. We revealed that patients with high WAS expression were less sensitive to immunotherapy medications. Conclusion: In conclusion, our study identified that WAS was a prognostic biomarker and correlated with immune infiltrates in ccRCC.

The Efficacy of Cyclooxygenase-2 Inhibitors for the Male Treatment of Lower Urinary Tract Symptoms: A Systematic Review and Meta-Analysis.

To investigate the potential use of cyclooxygenase-2 (COX-2) inhibitors in the treatment of lower urinary tract symptoms (LUTS) in male patients, we conducted a comprehensive meta-analysis. Our study involved the identification and collection of randomized controlled trials (RCTs) from leading databases including PubMed, MEDLINE, EMBASE, and Cochrane Library. The primary objective of this analysis was to evaluate the effectiveness of COX-2 inhibitors for the treatment of LUTS. Our analysis involved six short-term (within 3 months) RCTs involving 707 patients. We found that COX-2 inhibitor treatment significantly improved the International Prostate Symptom Score (IPSS) of patients (mean difference [MD] = -2.99, 95% confidence interval (CI): -3.65 to -2.33, p < .00001), nocturia frequency (MD = -1.90; 95% CI: -3.18 to -0.61, p = .004), and maximum flow rate (Qmax) (MD = 1.02; 95% CI: 0.06 to 1.98, p = .04). However, no significant differences were found between patients in terms of changes in prostate-specific antigen (PSA) (MD = 0.02; 95% CI: -0.39 to 0.43, p = .92) and total prostate volume (TPV) (MD = -2.93; 95% CI: -6.45 to 0.59, p = .10). Therefore COX-2 inhibitors are an effective treatment for LUTS.

HBx promotes hepatocarcinogenesis by enhancing phosphorylation and blocking ubiquitinylation of UHRF2.

BACKGROUND AND AIMS: The major cause of Hepatocellular carcinoma (HCC) is acute or chronic infection caused by hepatotropic viruses and HBV infection is the main cause. UHRF2, a ubiquitin-protein ligase E3, is associated with cancer development. This study aimed to investigate the connection and mechanism between UHRF2 and HBV-associated HCC. METHODS: The expression of UHRF2 in human HBV-positive HCC tissues and paracancerous tissues was detected by western blot and tissue microarray. The effects of UHRF2 on invasion, migration and proliferation were detected in HBV-positive hepatoma cell lines. Furthermore, western blot, immunofluorescence, Co-immunoprecipitation and ubiquitination assays were used to explore the relationship and mechanism between UHRF2 and HBV-associated HCC. RESULTS: HBV-positive HCC tissues had higher UHRF2 expression levels than adjacent non-tumor tissues. The HBV-positive HCC patients with a low UHRF2 level in cancer tissues had longer overall and recurrence-free survival compared with those with a high UHRF2 level. UHRF2 induced invasion, migration and proliferation in human HBV-positive HCC cell lines HepG2.2.15 and Hep AD38(-). HBx, an encoding protein of HBV, maintained the stability of UHRF2 by blocking the ubiquitination of UHRF2. HBx up-regulated CDK2 expression through ETS1. UHRF2 bound to CDK2 directly and enhanced UHRF2 phosphorylation at serine 643. CONCLUSIONS: These results suggest that HBx-ETS1-CDK2-UHRF2 pathway plays an important role in the pathogenesis of HBV-associated HCC and represents new therapeutic targets for human HCC. CLINICAL TRIALS REGISTRATION: ChiCTR2000041416.

Multi-longitudinal mode fiber laser sensor system with high signal-to-noise ratio based on laser modes control.

A multi-longitudinal mode fiber laser sensor (MLMFLS) system with high signal-to-noise ratio (SNR) is proposed. To the best of authors' knowledge, this is the highest SNR ever reported by MLMFLS system. The laser sensor consists of a narrow-band fiber Bragg grating (FBG), erbium-doped fiber (EDF) and an optical reflector. The FBG controls the number of laser modes which excited by laser sensor. Beat frequency signals (BFS) modulated by applied measurand are generated by those laser modes and their SNR are controlled by the FBG. Measurement results show the BFS have SNR of 65.0 dB, accuracy of ± 2.0 µÎµ, and stability of 0.4 kHz, which demonstrate its high SNR, accuracy and stability.

Folate deficiency inhibits the PCP pathway and alters genomic methylation levels during embryonic development.

Folate deficiency results in abnormal embryonic development, but the underlying mechanisms remain to be comprehensively investigated. Mutation of Vangl genes belonging to the planar cell polarity (PCP) pathway is associated with abnormal embryonic development, but the effect of folate deficiency on the PCP pathway is unclear. In this study, we found that folate deficiency inhibited Vangl gene expression and Vangl protein binding to the ligand Dvl. As a methyl donor, folate can chemically alter the DNA methylation levels of genomic sequences. Here, reduced representation bisulfite sequencing (RRBS) was employed to detect the methylation profiles of mouse embryos. The results confirmed that folate deficiency affected the genomic methylation levels of mouse embryos, which resulted in down-regulation of key genes involved in embryonic development. Gene ontology (GO) analysis suggested that the genes located in the differentially methylated regions (DMRs) are primarily involved in biological regulation, cellular processes, development, metabolism, and signaling pathways. The data revealed that folate deficiency inhibits the PCP pathway and alters genomic methylation profiles, which may be the underlying mechanisms through which folate deficiency impairs embryonic development.

Rapamycin inhibits spermatogenesis by changing the autophagy status through suppressing mechanistic target of rapamycin-p70S6 kinase in male rats.

Rapamycin (sirolimus) is an antiproliferative drug that has been widely used in the clinic as an immunosuppressant and a potential anticancer agent. Certain reports have indicated that rapamycin may induce male infertility through impairing sperm quality. The present study investigated the mechanism of male infertility caused by rapamycin and examined whether withdrawal of rapamycin could recover the number of sperm in rats. Male Sprague­Dawley rats (n=100) were divided randomly into 5 groups: 3 rapamycin­treated groups (2, 4 and 6 mg/kg) and 2 control groups [Blank and dimethyl sulfoxide (DMSO)]. Organ coefficients of the testes, number of sperm and hematoxylin­eosin staining analyses demonstrated that rapamycin treatment markedly damaged the structure of the seminiferous tubule and reduced the number of sperm. Immunohistochemistry of mechanistic target of rapamycin (mTOR) and Ki67 in testes tissue, and western blotting of phosphorylated­p70S6K and p70S6K, supported the hypothesis that rapamycin causes sperm reduction through inhibiting proliferation of spermatogonia. Unfortunately, 24 weeks after cessation of rapamycin treatment, only the number of sperm in 2 mg/kg group was restored back to the normal level. In addition, to the best of our knowledge, the present study was the first to demonstrate that low doses rapamycin leads to activation of autophagy in rat testes. This may be a self­protective mechanism of the cell in response to external stress. Thus, spermatogenesis can be recovered in the testes from rats in the low dose group. High doses of rapamycin resulted in excessive consumption of autophagy proteins, and the damage could not be compensated. In addition, it was revealed that cell apoptosis increased after treatment with rapamycin. In conclusion, the present study demonstrated that rapamycin inhibits spermatogenesis through suppressing phosphorylation of p70S6K and changing the autophagy status, ultimately reducing the number of sperm. These findings provide important guidance for the clinical application of rapamycin.

Expression of DROSHA in the Uterus of Mice in Early Pregnancy and Its Potential Significance During Embryo Implantation.

Previous studies have shown that microRNAs are involved in the process of implantation. They play an important role in cell growth and proliferation. DROSHA is the microRNA-processing enzyme and is required for the maturation of microRNAs. However, its expression and function during early pregnancy in mice still remain unclear. In the present study, we analyzed the expression pattern of DROSHA in the mouse uterus during early pregnancy, pseudopregnancy, artificially induced decidualization, and in the ovariectomized mouse uterus using real-time quantitative polymerase chain reaction, Western blotting analyses, and immunohistochemistry. We found that DROSHA was spatiotemporally expressed in decidualizing stromal cells during early pregnancy and in pseudopregnant mice in which decidualization was artificially induced. In the ovariectomized mouse uterus, the expression of DROSHA was upregulated after progesterone treatment. In a stromal cell culture model, the expression of DROSHA gradually increased with the progression of stromal decidualization. Taken together, our findings suggest that DROSHA is involved in stromal decidualization and may play an important role in embryo implantation in mice.

PbS Quantum-Dot Depleted Heterojunction Solar Cells Employing CdS Nanorod Arrays as the Electron Acceptor with Enhanced Efficiency.

Depleted heterojunction (DH) solar cells have shown great potential in power conversion. A 3-D DH structure was first designed and fabricated through a layer-by-layer spin-coating technique to increase the interfacial contact of p-type PbS quantum dots (QDs) and n-type CdS nanorod arrays. As a result, a decent power conversion efficiency of 4.78% in this structure was achieved, which is five times the efficiency of a planar heterojunction structure of a similar thickness. In the 3-D DH structure, n-type CdS nanorod arrays (NRs) were grown vertically as electron acceptors, on which p-type PbS quantum dots were deposited as absorbing materials in a layer-by-layer spin-coating fashion. The results are discussed in view of effective transportation of electrons through CdS NRs than the hopping transportation in large nanoparticle-based CdS film, the enlarged interfacial area, and shortened carrier diffusion distance.

Folate deficiency impairs decidualization and alters methylation patterns of the genome in mice.

Existing evidence suggests that adverse pregnancy outcomes are closely related with dietary factors. Previous studies in mice have focused on the harm of folate deficiency (FD) on development of embryo, while the effect of low maternal folate levels on maternal intrauterine environment during early pregnancy remains unclear. Since our previous study found that FD treatment of mice causes no apparent defects in embryo implantation but is accompanied by female subfertility, we next chose to investigate a potential role of FD on molecular events after implantation. We observed that the decidual bulges began to be stunted on pregnancy day 6. The results of functional experiments in vivo and in vitro showed that FD inhibited the process of endometrial decidualization. It has been confirmed that DNA methylation participates in decidualization, and folate as a methyl donor could change the methylation patterns of genes. Thus, we hypothesized that FD impairs maternal endometrial decidualization by altering the methylation profiles of related genes. Reduced representation bisulphite sequencing was carried out to detect the methylation profiles of endometrium on pregnancy day 6-8, which is equivalent to the decidualization period in mice. The results confirmed that FD changes the methylation patterns of genome, and GO analysis of the differentially methylated regions revealed that the associated genes mainly participate in biological adhesion, biological regulation, cell proliferation, development, metabolism and signalling. In addition, we found some candidates for regulators of decidual transformation, such as Nr1h3 and Nr5a1. The data indicate that FD inhibits decidualization, possibly by altering methylation patterns of the genome in mice.

Mouse Endometrium Temporal and Spatial Expression mRNA and MicroRNA Associated With Embryo Implantation.

Embryo implantation is a dynamic physiological process involving morphological and molecular changes in the endometrium during the pre-receptivity, receptivity, and implantation phases. A comprehensive analysis of messenger RNA (mRNA) and microRNA (miRNA) profiles during implantation will likely provide new clues to elucidate the underlying mechanisms governing embryo implantation. We characterized the mRNA and miRNA transcriptomes using next generation sequencing (NGS) of the endometrium 1 day postcoitum (dpc) and 4dpc and the implantation site (IMS) and inter-implantation (IIM) site of the endometrium on 5dpc. Real-time quantitative polymerase chain reaction was performed on selected miRNAs and their predicted target mRNAs to validate their negatively correlated expression. Statistical analysis of the data based on Gene Ontology (GO) group annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that the genes with significant expression at the IIM site were primarily involved in glucose, protein, and lipoprotein metabolism to provide energy for embryo implantation, while the genes identified at the IMS were involved in RNA functions to produce proteins in support of embryo development and trophoblast invasion. Extracellular matrix (ECM)-receptor interactions between cells and the ECM was the most remarkable event during implantation. The miRNA-mRNA interaction network unraveled the regulatory relationship between miRNAs and mRNAs. Hub miRNAs (mmu-miR-96 and mmu-miR-200b) were identified to target B-cell lymphoma 2 (Bcl-2), Kruppel-like factor 13 (Klf13), and Progesterone receptor (PGR), which are associated with the preparation of the receptive condition or the maintenance of early pregnancy.

Sodium fluoride activates ERK and JNK via induction of oxidative stress to promote apoptosis and impairs ovarian function in rats.

The toxicity of sodium fluoride (NaF) to female fertility is currently recognized; however, the mechanisms are unclear. Previously, we reported a reduction in successful pregnancy rates, ovarian atrophy and dysfunction following exposure to NaF. The purpose of this study was to elucidate the underlying molecular mechanisms. Female Sprague-Dawley rats (10 rats/group) received 100 or 200mg/L NaF in their drinking water for 6 months or were assigned to an untreated control group. Apoptotic indices and oxidative stress indicators in blood and ovarian tissue were analyzed following sacrifice. The results confirmed the NaF-induced ovarian apoptosis, with concomitant activation of oxidative stress. Further investigations in ovarian granular cells showed that exposure to NaF activated extracellular regulated protein kinase (ERK) and c-Jun NH2 kinase (JNK), disrupting the ERK and JNK signaling pathways, while p38 and PI3K remained unchanged. These data demonstrated that oxidative stress may play a key role in NaF-induced ovarian dysfunction by activating the apoptotic ERK and JNK signaling pathways.

The differential expression of microRNAs between implantation sites and interimplantation sites in early pregnancy in mice and their potential functions.

Embryo implantation is a complex process that involves synchronized crosstalk between a receptive endometrium and a functional blastocyst. It can take place only during the window of implantation, a period when a series of changes in gene expression occur in the endometrium to accept the embryo. As modulators of gene expression, microRNAs (miRNAs) have been identified as regulators of embryo implantation. To better understand how miRNAs regulate implantation and the related molecular mechanisms, we compared the expression profiles of miRNAs and messenger RNAs between implantation sites (IMs) and inter-IMs in the endometrium of pregnant mice on day 5 by microarrays. The results showed that compared with inter-IMs, 30 miRNAs were upregulated and 42 miRNAs (>2-fold) were downregulated at the IMs. By combining the results of the microarray experiments, we found that 20 upregulated pathways and 14 downregulated pathways might be subject to miRNA regulation at IMs. We also found that some miRNAs and their targets may play a key role in implantation.

Costimulatory molecule CD28 participates in the process of embryo implantation in mice.

Embryo implantation is a complex process requiring reciprocal interactions between implantation-competent blastocysts and receptive uteri. Accumulating literatures have indicated that T cells are involved in this process. The first signal mediated by T-cell receptor/CD3 complex and the second signal delivered by costimulatory molecules are essential for the differentiation of T cell into an effector cell. Expression and function of CD28, an important costimulatory molecule, during early pregnancy in mice is still unclear. In the present study, we investigated the expression pattern of CD28 in mouse uterus during early pregnancy and pseudopregnancy by real-time quantitative polymerase chain reaction, Western blotting, in situ hybridization, and immunohistochemistry (IHC). We found that injection of the uterine horn with CD28 antisense oligodeoxynucleotides leads to a decreased number of implantation sites. The expression pattern of CD3 protein examined by IHC is similar to that of CD28. These findings suggest that CD28 participates in the process of embryo implantation in mice, which might play its role through delivering the second costimulatory signal.

Mmu-microRNA-200a overexpression leads to implantation defect by targeting phosphatase and tensin homolog in mouse uterus.

Successful mouse embryo implantation requires a receptive uterus and an activated blastocyst. A large number of genes, cytokines, and other factors are involved in the process. MicroRNAs (miRNAs) regulate the expression of many genes, and previous studies have investigated the relationship between miRNA expression and embryo implantation. In this study, we show that mmu-microRNA-200a (mmu-miR-200a) is expressed in a spatiatemporal manner during implantation in mouse uterus and found that phosphatase and tensin homolog (PTEN), SON, and programmed cell death 4 (Pdcd4) are the target genes of mmu-miR-200a by bioinformatics analysis. In vitro gain and loss of function experiments confirm that PTEN, a critical gene for cell proliferation and apoptosis, is the target gene of mmu-miR-200a. Our experiments also show that injection of the uterine horn with mmu-miR-200a lentivirus leads to a decreased implantation rate. Collectively, our results suggest that mmu-miR-200a affects embryo implantation by regulating PTEN protein expression. Thus, clarifying the physiological functions of uterine miRNAs will help to elucidate the embryo implantation process and may even contribute to curing infertility and inventing new contraceptives.

The associations of high birth weight with blood pressure and hypertension in later life: a systematic review and meta-analysis.

The 'fetal origin hypothesis' suggests that metabolic diseases are directly related to poor nutritional status in early life. Thus, a high birth weight (HBW) may pose a lower risk than normal birth weight. Overweight and overnutrition are among the most widely recognized risk factors of metabolic diseases. To explore the possible effects of HBW on blood pressure and hypertension, a systematic review was performed. The PubMed and Embase databases were searched for relevant studies. The outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP) and hypertension. We included all of the studies that assessed the differences in outcomes for children aged >1 year between those born with normal birth weight (birth weight between 2500 and 4000 g or between the 10th and 90th percentiles for their gestational age) and those born with HBW (birth weight4000 g or 90th percentile for their gestational age). The outcomes were analyzed descriptively and by conducting a meta-analysis. Thirty-one studies satisfied the inclusion criteria. The mean difference in blood pressure and the relative risk of hypertension between individuals with HBW and individuals with normal birth weight was inversely associated with age. SBP and DBP, as well as the prevalence of hypertension, were higher in younger children with HBW but lower in older adults with HBW compared with individuals with normal birth weight. The findings suggested that an individual with HBW is prone to hypertension and higher blood pressure during childhood. However, a 'catch-down' effect in the elevation of blood pressure is observed in subjects with HBW as they grow older. Thus, older individuals with HBW are less susceptible to hypertension than those with normal birth weight.