Quantitative Hepatitis B Surface Antigen Predicts Hepatitis B Transmission in Infants Born to e Antigen-positive Mothers.

GOALS: This study aimed to explore whether quantitative surface antigen [hepatitis B surface antigen (HBsAg)] can be used as a surrogate marker of hepatitis B virus (HBV) DNA to predict hepatitis B transmission before the first hepatitis vaccine dose in infants born to hepatitis B e antigen (HBeAg)-positive pregnant women. BACKGROUND: Currently, HBV transmission persistently occurs worldwide, especially in infants born to e antigen (HBeAg)-positive highly viremic mothers. However, due to high cost, the extensive use of viral load testing to identify these high-risk mothers is limited. MATERIALS AND METHODS: In total of 275 HBeAg-positive pregnant women paired with 280 infants were enrolled in this study. Quantitative HBsAg and HBV DNA levels were measured in the third trimester. Spearman rank correlation was used to assess the correlation between HBsAg levels and viral load, and multivariate logistic regression to identify factors related to HBV transmission in infants. RESULTS: Among 280 infants included, 15 (5.4%) infants were infected with HBV. In this study, we observed that quantitative HBsAg was positively correlated with maternal viral load (r=0.70, P<0.001) and highly predicted HBV transmission in infants born to HBeAg-positive mothers with area under the curve of 0.76 (95% confidence interval, 0.71-0.81). The optimum threshold HBsAg levels above 4.6 log10 IU/mL to predict HBV transmission in infants had a sensitivity of 80.0%, specificity of 67.9%. CONCLUSIONS: Quantitative HBsAg could be used as a surrogate marker of HBV DNA levels to predict hepatitis B transmission occurring before the injection of first-dose vaccine in infants born to e antigen-positive mothers.

Maternal syphilis treatment and pregnancy outcomes: a retrospective study in Jiangxi Province, China.

BACKGROUND: Studies investigating the associations of maternal syphilis treatment with birth outcomes mainly concentrated in economically developed areas. Limited data are available in economically underdeveloped areas, such as Jiangxi Province. The study aims to investigate the impact of maternal treatment on birth outcomes in Jiangxi Province, China. METHODS: Data were obtained from the China's Information System of Prevention of Mother-to-Child Transmission in Jiangxi Province. All syphilis infected pregnant women who delivered ≥28 gestational weeks and were registered in this system between 1 January 2013 and 31 December 2019 were enrolled. Pregnancy outcomes were evaluated by group-specific analyses according to their treatment status, adequacy and initiation time. RESULTS: 4210 syphilis infected pregnant women were included in the analyses. Infants born to untreated mothers (n = 1364) were at significantly higher risk for stillbirth (adjusted odds ratio (aOR) = 1.74, 95% CI, 1.01-3.00, P = 0.045), preterm birth (aOR = 1.27, 95% CI, 1.02-1.59, P = 0.034) and low birth weight (LBW) (aOR = 1.44; 95% CI, 1.11-1.86, P = 0.006) than those born to treated mothers (n = 2846) after adjustment for confounding factors. A significantly higher risk of stillbirth (aOR = 3.68; 95% CI, 1.62-8.34, P = 0.002), preterm birth (aOR = 2.26; 95% CI, 1.71-3.00, P < 0.001), LBW (aOR = 2.23; 95% CI, 1.59-3.14, P < 0.001) and congenital syphilis (CS) (aOR = 3.63; 95% CI, 1.80-7.31, P < 0.001) was found in infants exposed to mothers treated inadequately (n = 1299) than those treated adequately (n = 1547). No pregnant women who initiated the treatment in the first trimester (n = 682) delivered a neonatal CS case. Compared with mothers who initiated treatment in the first trimester (n = 682), those initiated in the third trimester (n = 1234) suffered an increased risk of stillbirth (aOR = 4.48; 95% CI, 1.31-15.30, P = 0.017), preterm birth (aOR = 2.34; 95% CI, 1.61-3.40, P < 0.001) and LBW (aOR = 3.25; 95% CI, 1.97-5.37, P < 0.001). CONCLUSIONS: Maternal treatment, especially early and adequate treatment, plays a crucial role in mitigating adverse pregnancy outcomes among syphilis infected women.

Incidence and Risk Factors of Intrauterine Transmission Among Pregnant Women With Chronic Hepatitis B Virus Infection.

GOALS: To identify the potential risk factors of hepatitis B virus (HBV) intrauterine transmission and predict the incidence of HBV intrauterine transmission among hepatitis B surface antigen-positive pregnant women with diverse viral load. BACKGROUND: The intrauterine transmission of HBV significantly contributes to the persistence of a high number of patients infected with HBV. However, its risk factors remain unclear. MATERIALS AND METHODS: A prospective study was performed on hepatitis B surface antigen-positive pregnant women who delivered from June 2012 to December 2016 at Wuhan Medical Care Center for Women and Children, Wuhan, China. RESULTS: In total, 1200 women paired with 1219 infants were enrolled. In total, 11 (0.9%) infants were identified with intrauterine transmission. We observed that all infants with intrauterine transmission were born to hepatitis B e antigen-positive mothers who had serum HBV DNA levels >7 log10 copies/mL. Our study suggested that the HBV DNA levels (for each log10 copies/mL increase, odds ratio=5.43; 95% confidence interval, 1.31-22.43; P=0.019) had independent effects on HBV intrauterine transmission in a multivariate logistic regression model. Moreover, cesarean section (odds ratio=0.18; 95% confidence interval, 0.04-0.74; P=0.018) was associated with a reduced risk of HBV intrauterine transmission. The predictive rates of intrauterine transmission were 0.06%, 0.50%, 2.81%, 8.89% in infants with maternal HBV DNA levels of 10, 10, 10, 10 copies/mL, respectively. CONCLUSIONS: Our data confirmed that increasing maternal viral load has the ability to predict intrauterine HBV transmission. Vaginal delivery increased risk of HBV transmission in infants compared with cesarean section. Further studies are warranted to clarify the possible mechanism underlying these associations.

Maternal hepatitis B surface antigen carrier status increased the incidence of gestational diabetes mellitus.

BACKGROUND: The relationship between chronic hepatitis B virus (HBV) infection with gestational diabetes mellitus (GDM) remains unclear. This study aimed to identify the association between maternal HBsAg-positive status and GDM. METHODS: A retrospective cohort study was performed on the pregnant women who delivered from June 2012 to May 2016 at Wuhan Medical Care Center for Women and Children, Wuhan, China. We compared the incidence of GDM between HBsAg-positive pregnant women and HBsAg-negative controls. A multivariate regression model was used to measure the independent association between maternal HBsAg carrier and the risk of developing GDM. RESULTS: In total, 964 HBsAg-positive pregnant women and 964 HBsAg-negative women were included into the study. We observed maternal HBsAg carrier (OR 1.47, 95% CI 1.06-2.03), age (OR 1.05, 95% CI 1.00-1.10) and family history of diabetes (OR 3.97, 95% CI 2.05-7.67) had an independent risk for GDM in multivariable logistical regression model. However, no significant association was found between HBeAg carrier status, other HBV markers or viral load in pregnancy and the incidence of GDM. CONCLUSIONS: Our results indicated that maternal HBsAg carriage is an independent risk factor for GDM, but viral activity indicated by HBeAg status and viral load is not the main reason for this phenomenon. Further studies are warranted to clarify the possible mechanisms behind such association of HBV infection and the additional risk of GDM.

Inhibition of miR-9-5p suppresses prostate cancer progress by targeting StarD13.

BACKGROUND: This study aims to investigate the effects of inhibiting microRNA-9-5p (miR-9-5p) on the expression of StAR-related lipid transfer domain containing 13 (StarD13) and the progress of prostate cancer. METHODS: The mRNA expression levels of miR-9-5p and StarD13 were determined in several prostate cancer cell lines. We chose DU145 and PC-3 cells for further research. The CCK8 assay was used to measure the cell viability. The cell invasion and wound-healing assays were respectively applied to evaluate invasion and migration. The expression of E-cadherin (E-cad), N-cadherin (N-cad) and vimentin were measured via western blot. DU145 and PC-3 cells overexpressing StarD13 were generated to investigate the variation in proliferation, invasion and migration. A luciferase reporter assay was used to identify the target of miR-9-5p. RESULTS: Our results show that miR-9-5p was highly expressed and StarD13 was suppressed in prostate cancer cells. MiR-9-5p inhibition repressed the cells' viability, invasion and migration. It also increased the expression of E-cad and decreased that of N-cad and vimentin. StarD13 overexpression gave the same results as silencing of miR-9-5p: suppression of cell proliferation, invasion and migration. The bioinformatics analysis predicted StarD13 as a target gene of miR-9-5p. Quantitative RT-PCR, western blot analysis and the dual-luciferase reporter assay were employed to confirm the prediction. CONCLUSION: Our results show that miR-9-5p plays a powerful role in the growth, invasion, migration and epithelial-mesenchymal transition (EMT) of prostate cancer cells by regulating StarD13. A therapeutic agent inhibiting miR-9-5p could act as a tumor suppressor for prostate cancer.

Genetic variations in LTA gene and PDCD1 gene and intrauterine infection of hepatitis B virus: a case-control study in China.

Intrauterine infection with hepatitis B virus (HBV) has been suggested to accounting for most cases of chronic HBV infection, which cannot be blocked by combined immunoprophylaxis. The fact that the genetic background might impact the susceptibility to intrauterine infection of HBV has been identified by recent researches. A case-control study included sixty-nine HBsAg-positive mother-newborn pairs with intrauterine infection as cases compared to 138 mother-newborn pairs without intrauterine infection as controls. We studied the correlations between HBV intrauterine transmission and 15 maternal SNPs in eight genes (LTA, LTBR, TNFSF14, PDCD1, APOBEC3B, CD274, CD40 and CD40LG). There was a substantially significantly decreased risk of intrauterine infection of HBV in mothers with the rs2227981 TT genotype in PDCD1 gene compared to those with the rs2227981 GG genotype (OR 0.11, 95% CI 0.01-0.95, P = 0.045). Under recessive model (OR 0.51, 95% CI 0.26-1, P = 0.050) and additive model (OR 0.50, 95% CI 0.28-0.88, P = 0.017), we also found a marginally significantly decreased risk of intrauterine infection of HBV. Furthermore, under additive model, maternal genotype for rs2239704 in LTA gene was marginally significantly related to an increased risk of intrauterine HBV infection (OR 1.62, 95% CI 1-6.66, P = 0.055). However, there were no statistically significant associations among the remaining 13 SNPs and the risk of intrauterine infection of HBV. The examination implied that hereditary variants of PDCD1 and LTA genes were associated with intrauterine infection of HBV.

Amelioration of Cavernosal Fibrosis and Erectile Function by Lysyl Oxidase Inhibition in a Rat Model of Cavernous Nerve Injury.

BACKGROUND: Cavernous nerve injury (CNI) causes fibrosis and loss of smooth muscle cells (SMCs) in the corpus cavernosum and leads to erectile dysfunction, and lysyl oxidase (LOX) activation has been found to play an important role in fibrotic diseases. AIM: To evaluate the role of LOX in penile fibrosis after bilateral CNI (BCNI). METHODS: Rats underwent BCNI or a sham operation and were treated with vehicle or ß-aminopropionitrile, a specific LOX activity inhibitor. 30 days after BCNI, rats were tested for erectile function before penile tissue harvest. LOX and extracellular matrix component expression levels in the corpus cavernosum, including matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), fibronectin (FN), collagen (COL) I, and COL IV, were evaluated by real-time quantitative polymerase chain reaction and western blot. Corporal fibrosis was evaluated by Masson trichrome staining. Localization of LOX and SMC content in the corpus cavernosum were assessed by immunohistochemistry. OUTCOMES: Ratio of intracavernous pressure to mean arterial blood pressure; LOX, MMPs, TIMPs, COL I, COL IV, and FN expression; penile fibrosis; penile SMC content. RESULTS: After BCNI, there was an increase in penile LOX expression and activity, increased penile fibrosis, decreased SMC content, and impaired erectile function. TIMP1, TIMP2, COL I, COL IV, and FN expression was markedly upregulated, whereas the enzyme activity of MMPs was decreased after BCNI. ß-Aminopropionitrile treatment, at least in part, prevented a decrease in the ratio of intracavernous pressure to mean arterial blood pressure, decreased penile expression of TIMP1, TIMP2, COL I, COL IV, and FN, increased MMP activity, prevented corporal fibrosis, and preserved SMC content. CLINICAL TRANSLATION: LOX over-activation contributes to penile fibrosis and LOX inhibition could be a promising strategy in preventing the progression of CNI-induced erectile dysfunction. STRENGTHS AND LIMITATIONS: This is the 1st study to demonstrate the role of LOX activation in penile fibrosis. However, the exact mechanism of how LOX influences extracellular matrix protein synthesis and SMC content preservation awaits further investigation. CONCLUSION: CNI induced LOX over-activation in cavernous tissue, and inhibition of LOX preserved penile morphology and improved erectile function in a rat model of BCNI. Wan Z-H, Li G-H, Guo Y-L, et al. Amelioration of Cavernosal Fibrosis and Erectile Function by Lysyl Oxidase Inhibition in a Rat Model of Cavernous Nerve Injury. J Sex Med 2018;15:304-313.

Maternal Hepatitis B Virus Infection and Pregnancy Outcomes: A Hospital-based Case-control Study in Wuhan, China.

GOALS: To examine the impact of maternal hepatitis B virus infection on pregnancy outcomes. BACKGROUND: Studies regarding hepatitis B virus infection and pregnancy outcomes are limited with inconsistent results, and none of them have evaluated the effect of maternal viral load in pregnancy on pregnancy outcomes. STUDY: A hospital-based case-control study was conducted. In total, 1728 hepatitis B surface antigen (HBsAg)-positive women who delivered consecutively at Wuhan Women and Children Medical and Healthcare Center, Wuhan, China, from June 2008 to May 2015, were compared with 1497 HBsAg-negative women giving birth in the same hospital during the same period who were randomly identified and selected from the computerized medical record database in parallel. Univariate and multivariate logistic regression models were constructed. RESULTS: After adjusting for confounding variables, maternal HBsAg carriage was associated with increased risk of pregnancy-induced hypertension [adjusted odds ratio (aOR)=2.20; 95% confidence interval (CI), 1.30-3.73], fetal distress (aOR=1.40; 95% CI, 1.09-1.78), cesarean delivery (aOR=1.70; 95% CI, 1.45-1.99), and macrosomia (aOR=1.68; 95% CI, 1.19-2.37). Moreover, maternal viral load in the second trimester was significantly associated with risk of preterm birth (aOR for each log10 copy/mL increase, 1.18; 95% CI, 1.01-1.39) among HBsAg carriers after adjustment for maternal age, employment, parity, history of abortion, and prenatal body mass index. CONCLUSIONS: Maternal HBsAg carriage was associated with several adverse pregnancy outcomes. Furthermore, hepatitis B viral activity in pregnancy might have certain effects on pregnancy outcomes. Careful surveillance of maternal HBsAg status as well as viral activity in the second trimester among HBsAg carriers is warranted.

Efficacy of metformin on pregnancy complications in women with polycystic ovary syndrome: a meta-analysis.

OBJECTIVE: To evaluate the efficacy of metformin administration throughout pregnancy on pregnancy-related complications in women with polycystic ovary syndrome (PCOS). STUDY DESIGN: MEDLINE and ScienceDirect were searched to retrieve relevant trials. The endpoint was the incidence of complications of pregnancy, gestational diabetes mellitus (GDM), pre-eclampsia (PE), miscarriage and premature birth included. RESULTS: Five studies with 502 PCOS patients with metformin administration throughout pregnancy and 427 controls who used metformin just to get conception were included in our meta-analysis. In study group, a significantly lower change of emerging miscarriage and premature birth was observed, the pooled relative risk (RR) was 0.32 (95% confidence interval (CI): 0.19-0.56) for miscarriage and 0.40 (95%CI: 0.18-0.91) for premature birth. No significant difference was demonstrated in emerging GDM and PE. CONCLUSIONS: Metformin therapy throughout pregnancy can reduce the RR of miscarriage and premature birth incidence in PCOS patients with no serious side effects.

Calpain Inhibition Improves Erectile Function in a Rat Model of Cavernous Nerve Injury.

INTRODUCTION: Erectile dysfunction (ED) after cavernous nerve (CN) injury remains difficult to treat. Calpain plays a critical role in causing neurodegenerative diseases. This study aimed to evaluate whether calpain inhibition preserves erectile function in a rat model of CN injury. MATERIALS AND METHODS: Rats underwent sham surgery or CN crush injury. The CN-crushed rats were treated with vehicle or MDL-28170, a specific calpain inhibitor. At 1, 2, 3, and 7 days post-surgery, major pelvic ganglia (MPG) were harvested, followed by the measurement of erectile function, respectively. At 28 days, penile tissue and distal CN were harvested, followed by the measurement of erectile function in rats. Calpain activity in MPG and corpus cavernosum, as well as TGF-ß1/Smad2 and collagen content in corpus cavernosum, were measured by western blot. Neuronal nitric oxide synthase (nNOS) was observed by immunohistochemistry. RESULTS: Increased calpain activity was observed in MPG and corpus cavernosum. CN crush markedly attenuated the erectile responses and nNOS expression in CN, and these were improved by MDL-28170 treatment. Furthermore, treatment prevented increased TGF-ß1/Smad2 and collagen expression in corpus cavernosum. CONCLUSIONS: Our results suggested that calpain activation plays a role in pathogenesis of CN injury-associated ED. Calpain inhibition could be a novel approach for preventing the development of ED following CN injury.

Synthesis, Antiviral Bioactivity of Novel 4-Thioquinazoline Derivatives Containing Chalcone Moiety.

A series of novel 4-thioquinazoline derivatives containing chalcone moiety were designed, synthesized and systematically evaluated for their antiviral activity against TMV. The bioassay results showed that most of these compounds exhibited moderate to good anti-TMV activity. In particular, compounds M2 and M6 possessed appreciable protection activities against TMV in vivo, with 50% effective concentration (EC50) values of 138.1 and 154.8 µg/mL, respectively, which were superior to that of Ribavirin (436.0 µg/mL). The results indicated that chalcone derivatives containing 4-thioquinazoline moiety could effectively control TMV. Meanwhile, the structure-activity relationship (SAR) of the target compounds, studied using the three-dimensional quantitative structure-activity relationship (3D-QSAR) method of comparative molecular field analysis (CoMFA) based on the protection activities against TMV, demonstrated that the CoMFA model exhibited good predictive ability with the cross-validated q2 and non-cross-validated r2 values of 0.674 and 0.993, respectively. Meanwhile, the microscale thermophoresis (MST) experimental showed that the compound M6 may interaction with the tobacco mosaic virus coat protein (TMV CP).

Prognostic value and immune landscapes of anoikis-associated lncRNAs in lung adenocarcinoma.

BACKGROUND: Methods for predicting the outcome of lung adenocarcinoma (LUAD) in the clinic are limited. Anoikis is an important route to programmed cell death in LUAD, and the prognostic value of a model constructed with anoikis-related lncRNAs (ARlncRNAs) in LUAD is unclear. METHODS: Transcriptome and basic information for LUAD patients was obtained from the Cancer Genome Atlas. Coexpression and Cox regression analyses were utilized to identify prognostically significant ARlncRNAs and construct a prognostic signature. Furthermore, the signature was combined with clinical characteristics to create a nomogram. Finally, we performed principal component, enrichment, tumor mutation burden (TMB), tumor microenvironment (TME) and drug sensitivity analyses to evaluate the basic research and clinical merit of the signature. RESULTS: The prognostic signature developed with eleven ARlncRNAs can accurately predict that high-risk group patients have a worse prognosis, as proven by the receiver operating characteristic (ROC) curve (AUC: 0.718). Independent prognostic analyses indicated that the risk score is a significant independent prognostic element for LUAD (P<0.001). In the high-risk group, enrichment analysis demonstrated that glucose metabolism and DNA replication were the main enrichment pathways. TMB analysis indicated that the high-risk group had a high TMB (P<0.05). Drug sensitivity analyses can recognize drugs that are sensitive to different risk groups. Finally, 11 ARlncRNAs of this signature were verified by RT-qPCR analysis. CONCLUSIONS: A novel prognostic signature developed with 11 ARlncRNAs can accurately predict the OS of LUAD patients and offer clinical guidance value for immunotherapy and chemotherapy treatment.

circ-ATAD1 as Competing Endogenous RNA for miR-191-5p Forces Non-small Cell Lung Cancer Progression.

The association of circular RNAs (circRNAs) with non-small cell lung cancer (NSCLC) has been recognized extensively. In view of this, our study particularly surveyed the underlying mechanism of circ-ATAD1 in the disease. First, an analysis of the clinical expression of circ-ATPase family AAA domain containing 1 (ATAD1) was performed, followed by further evaluation of the relationship between circ-ATAD1 expression and prognosis. Then, A549 cells were treated with single transfection or combined transfection with the plasmid vectors that interfere with circ-ATAD1 or miR-191-5p. circ-ATAD1 and miR-191-5p levels were detected by reverse transcription quantitative polymerase chain reaction to verify the transfection success. Then, cell proliferation was checked by cell count kit-8 and clonal formation test. Cell apoptosis was analyzed by flow cytometry. Cell migration and invasion were examined by wound healing assay and Transwell. Finally, the targeting of miR-191-5p to circ-ATAD1 or Forkhead Box K1 (FOXK1) was verified by bioinformation website starBase analysis and dual-luciferase reporter assay. circ-ATAD1 was expressed abundantly in tumor tissues of NSCLC patients and had a predictive value in poor prognosis. circ-ATAD1 underexpression or miR-191-5p overexpression could obstruct A549 cells to behave aggressively, while circ-ATAD1 upregulation or miR-191-5p depletion resulted in the promotion of aggressiveness of A549 cells. Interestingly, circ-ATAD1 could decoy miR-191-5p. miR-191-5p negatively regulated FOXK1 expression, and downregulating miR-191-5p or upregulating FOXK1 rescued circ-ATAD1 downregulation-mediated influences on NSCLC cells. circ-ATAD1 accelerates NSCLC progression by absorbing miR-191-5p to upregulate FOXK1 expression.

Factors associated with congenital syphilis: A retrospective study in Jiangxi Province, China.

BACKGROUND: There are a lack of studies about factors influencing congenital syphilis (CS) in economically underdeveloped areas, such as Jiangxi Province, China. METHODS: A retrospective study was conducted based on the information system of prevention of mother-to-child transmission of syphilis management in Jiangxi Province, China. Pregnant women with syphilis infection who delivered ≥28 gestational weeks and registered in this system from 1 January 2013 to 2030 June 2018 were enrolled. Maternal characteristics and treatment regimens associated with CS were evaluated using multivariable regression analysis. RESULTS: 1196 syphilis infected mothers and their 1207 infants were included in the analyses, and 116 infants were diagnosed with CS, providing an overall incidence of 9.61% (116/1207). Multivariable logistic regression analysis showed that increasing maternal age was barely associated with the risk of CS (adjusted odds ratio (aOR) = 0.97, 95% CI, 0.93-1.00, p = .047). Women with a high nontreponemal serum test titer (≥1:8) had a 126% increased risk of delivering an infant with CS than those with a low titer (<1:8) (aOR = 2.26, 95% CI, 1.51-3.39, p < .001). The risk for CS decreased significantly in infants born to mothers receiving adequate treatment than those receiving no treatment (aOR = 0.36, 95% CI, 0.21-0.61, p < .001). CONCLUSIONS: Adequate treatment is critical for the prevention of CS. Further strategies focusing on early diagnosis and adequate treatment among syphilis infected pregnant women, particularly among those with younger age and high nontreponemal titer, should be strengthened to prevent CS.

Poly(ADP-Ribose) polymerase inhibition improves erectile function in diabetic rats.

INTRODUCTION: Erectile dysfunction (ED) is a common and hard-to-treat complication of diabetes mellitus (DM). Multiple lines of evidence have shown that poly(ADP-ribose) polymerase (PARP) activation plays an important role in neurovascular dysfunction in diabetes, which is the crucial mechanism for diabetic ED. AIM: To investigate the preventive benefit of a PARP inhibitor in a rat model of ED induced by diabetes. METHODS: Established streptozotocin-diabetic male Sprague-Dawley rats were given PJ-34, a selective PARP inhibitor, by oral gavage at a dose of 10 mg/kg twice daily for 8 weeks. Erectile responses under electrical stimulation of the cavernous nerve, PARP activity and reactive oxygen species (ROS) production were measured. Nitric oxide synthase (NOS) isoforms were evaluated by Western blot and real-time quantitative PCR. Nuclear factor-kappa B activition and apoptosis in corpus cavernosa (CC) were also investigated. MAIN OUTCOME MEASURES: The effects of PARP inhibition on the development of diabetic ED were determined. RESULTS: Diabetes markedly attenuated the erectile responses (intracavernosal pressure/mean systemic arterial blood pressure) and these were partially prevented by PJ-34 treatment. Promoted oxidative stress associated PARP activation was found in CC from vehicle-treated diabetic rats. PJ-34 blocked PARP activity and the diabetes-associated ROS generation. Decreased expression and activity of constitutive NOS (cNOS), including endothelial NOS (eNOS) and neuronal NOS (nNOS), associated with enhanced inducible NOS (iNOS) expression and activity were observed in vehicle-treated diabetic rats. Although PJ-34 had no effect on eNOS expression, it significantly prevented the decrease in nNOS expression and cNOS activity, and inhibited iNOS expression and activity in diabetic rats. PARP blockade by PJ-34 to some extent prevented diabetes-associated apoptosis and NF-κB activation. CONCLUSIONS: Our results indicate that PARP activation plays an important role in the pathogenesis of diabetic ED and PARP inhibition may be a promising strategy to prevent development of diabetic ED.

Theaflavin ameliorates renal ischemia/reperfusion injury by activating the Nrf2 signalling pathway in vivo and in vitro.

Studies have demonstrated that oxidaive stress-induced apoptosis may be the main pathogenic mechanism of renal ischemia/reperfusion (I/R) injury. Theaflavin, a polyphenolic compound extracted from black tea, has been proven to exert strong antioxidant biological function. The objective of the present study was to investigate the potential role of theaflavin on renal I/R injury and its potential molecular mechanism both in vitro and in vivo. C57/BL6 J mice were used to create a model of I/R injury wherein mice were ligated with bilateral renal pedicles for 45 min, and then reperfused for 24 h. A hypoxia/reoxygenation (H/R) model of TCMK-1 cells was used to simulate I/R in vitro. Theaflavin were administered to the treatment group first and then established the model. Kidney Injury Molecule-1 (KIM-1), serum creatinine, urea nitrogen, and 24-h urinary protein levels were evaluated and changes in mitochondrial membrane potential and the ultrastructure of mitochondria were observed. Cell viability, oxidative stress damage, and apoptosis were assessed. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes HO-1 and NQO1 were evaluated. Our results revealed that pretreatment with theaflavin significantly inhibited I/R- and H/R-induced renal injury and cell apoptosis. Theaflavin improved mitochondrial dysfunction by attenuating mitochondrial damage and promoting mitochondrial membrane potential. Theaflavin pretreatment significantly reduced malondialdehyde content, while enhancing superoxide dismutase activity in vivo and in vitro. It also reduced oxidative stress and apoptosis mainly by upregulating Nrf2 and its downstream targets in TCMK-1 cells. Thus, theaflavin exerted a protective effect against renal I/R injury by inhibiting oxidative stress and apoptosis via activation of the Nrf2-NQO1/HO-1 pathway as well as correcting mitochondrial dysfunction, thereby presenting its potential as a clinical therapeutic in cases of acute kidney injury.

circITGA7 Acts as a miR-370-3p Sponge to Suppress the Proliferation of Prostate Cancer.

Prostate cancer (PCa) refers to one of the most common tumors in male's genitourinary system. Emerging research has confirmed that circRNAs play an important role in the occurrence and development of tumors. However, the correlation between circular RNA circITGA7 and PCa still remains unclear. Here, the role of circITGA7 in PCa was explored and the underlying mechanism was investigated as well. The circRNA expression profiles in PCa and the paracancerous tissues were established by high-throughput sequencing. The expression levels of circITGA7 in PCa tissues and cells were detected by qRT-PCR. Cell Counting Kit-8, colony formation, EdU, and flow cytometry assays were used to detect the effects of circITGA7 on PCa cell proliferation. To further explore the underlying mechanisms, bioinformatics analysis on downstream target genes was carried out. RNA immunoprecipitation and dual-luciferase reporter assays were used to verify the direct relationship between miR-370-3p and circITGA7 or P21CIP1. The present results demonstrated that circITGA7 was downregulated in PCa tissues and cells. Gain- or loss-of-function assays showed that circITGA7 inhibited the proliferation of PCa cells in vivo and in vitro. Mechanically, circITGA7 served as a sponge for miR-370-3p, and miR-370-3p could target P21CIP1 in PCa cells. The inhibition of cell proliferation induced by circITGA7 could be reversed by transfecting miR-370-3p mimic. Collectively, our data indicated that circITGA7 played an important role in inhibiting tumor proliferation in PCa and might be a potential therapeutic target.

[Impact of adenovirus-mediated PDE5-shRNAs on the free calcium level in the smooth muscle cells of rat corpus cavernosum].

OBJECTIVE: To observe the influence of recombinant adenovirus-mediated PDE5-shRNAs on the free calcium level in rat penile smooth muscle cells and to explore the feasibility of gene therapy for erectile dysfunction (ED). METHODS: Smooth muscle cells of the rat corpus cavernosum were transfected with constructed rAd-rPDE5-shRNAs and then dyed with the calcium fluorescent probe Fluo-3/AM at 24, 48 and 72 hours. The dynamic changes of the calcium fluorescence intensity were observed under the laser scanning confocal microscope (LSCM). The relative level of intracellular calcium was determined by fluorescence indexes. RESULTS: The fluorescence indexes of calcium at 24, 48 and 72 hours were 829.3 +/- 7.8, 801.5 +/- 9.5 and 856.3 +/- 8.7 in the rAd-rPDES-shRNAs group, significantly lower than in the rAd-mock (1106.3 +/- 10.8, 1121.3 +/- 10.2 and 1058.5 +/- 12.1) and blank control group (1076.6 +/- 9.7, 1133.4 +/- 11.2 and 1104.3 +/- 10.5) (P < 0.05). CONCLUSION: Adenovirus mediated shRNAs of the target PDE5 gene can significantly decrease the intracellular calcium level in the smooth muscle cells of the rat corpus cavernosum.

[Impact of rAd5-shRNA- PDE5A3 on cGMP in the smooth muscle cells of human corpus cavernosum].

OBJECTIVE: To investigate the effect of phosphodiesterase type 5 (PDE5) small interfering RNA (siRNA) on cyclic guanosine monophosphatethe (cGMP) in the smooth muscle cells of human corpus cavernosum, and to provide laboratory evidence for the application of the RNA interference (RNAi) technique for the treatment of erectile dysfunction. METHODS: The recombinant adenovirus rAd5-shRNA-PDE5A3 expressing three pairs of specific shRNA was constructed successfully. The smooth muscle cells of human corpus cavernosum were divided into an experimental, a negative control and a blank control group, and transfected respectively with rAd5-shRNA-PDE5A3, adenovirus rAd5-mock and phosphate buffered saline. The concentration of cGMP was measured by radioimmunoassay at 24, 48 and 72 hours after transfection, and the effect of rAd5-shRNA-PDE5A3 was detected on the cGMP in the smooth muscle cells of the corpus cavernosum. RESULTS: The cGMP level in the smooth muscle cells of the corpus cavernosum was significantly higher in the rAd5-shRNA-PDE5A3 group than in the rAd5-mock control and blank control groups (P < 0.05), most significantly at 72 hours after transfection. CONCLUSION: The rAd5-shRNA-PDE5A3 can obviously increase the cGMP level in the smooth muscle cells of human corpus cavernosum, and enhance the inhibition of the PDE5 gene.

Cesarean section reduces the risk of early mother-to-child transmission of hepatitis B virus.

AIMS: To evaluate the effects of cesarean section (CS) on the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) among hepatitis B surface antigen (HBsAg) positive pregnant women. METHODS: A prospective cohort study was performed on HBsAg-positive pregnant women who delivered from June 2012 to March 2017 at Wuhan Medical Care Center for Women and Children in Wuhan, China. Logistic regression models were used to examine the associations between mode of delivery and the presence of HBV MTCT. RESULTS: A total of 1384 women paired with 1407 infants were enrolled. Our study showed that the incidence of HBV MTCT was 1.0% (14/1407) in infants born to HBsAg-positive pregnant women. We observed that the infants born by CS had a smaller percentage of HBV infection than those born by vaginal delivery (VD) (0.5% vs 1.7%, P = 0.043). In the fully adjusted model, CS was significantly associated with a decreased risk of HBV MTCT (OR = 0.26; 95% CI: 0.07-0.95; P = 0.042). CONCLUSION: Our data confirmed that CS has a protective effect on early MTCT of HBV. CS for HBeAg-positive mothers with high viral load could reduce risk of MTCT and may become a new preventive measure of HBV MTCT through research on its risk-benefit assessment.