MicroRNA-373-3p inhibits the growth of cervical cancer by targeting AKT1 both in vitro and in vivo.

OBJECTIVE: In this study, we aimed to investigate the function of microRNA-373-3p (miR-373-3p) in the pathogenesis of cervical cancer. METHODS: Human and mouse cervical cancer cell lines were transfected with miR-373-3p mimic and inhibitor. Cell proliferation and viability were evaluated with Cell Counting Kit-8 (CCK-8) assay and Lactate Dehydrogenase (LDH) assay, respectively. The AKT1-targeting role of miR-373-3p was analyzed by qPCR and Western blot. Finally, a mouse xenograft cervical tumor model was adopted to study the in vivo effect of miR-373-3p on tumor growth and the expression of AKT1. RESULTS: Over-expression of miR-373-3p significantly reduced the proliferation of cervical carcinoma cell line in vitro. In addition, miR-373-3p overexpression also inhibited cervical cancer growth in tumor-bearing mice. Mechanistically, we found that AKT1 gene can be targeted by miR-373-3p. MiR-373-3p mimic decreased the mRNA and protein expression of AKT1, while the miR-373-3p inhibitor increased the level of AKT1 in cervical cancer cells. AKT1 overexpression rescued the proliferation of cervical cancer cells transfected with miR-373-3p. CONCLUSION: MiR-373-3p can serve as a novel anti-tumor microRNA in cervical cancer by targeting AKT1.

[Relationship between the expression of HBV DNA, HBV cccDNA in human ovary tissues and the HBV intrauterine infection].

OBJECTIVE: To investigate the relationship between hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and HBV covalently closed circular DNA (cccDNA) in the ovary and HBV intrauterine infection. METHODS: HBV DNA and HBV cccDNA were assayed in the ovaries of 33 pregnant women who were positive for HBV DNA, tested by Fluorescent quantitative polymerase chain reaction (FQ-PCR). The level of HBV mark (HBVM) and the content of HBV DNA in peripheral blood of infants were measured by chemoluminescence and FQ-PCR methods respectively. RESULTS: The overall positive rate for both HBV DNA and HBV cccDNA in ovarian samples was 51.52% (17/33). The rate on intrauterine infection among infants was 12.12% (4/33) and all the 4 infected infants were delivered from mothers with normal hepatic function. When HBV DNA and HBV cccDNA were both positive, the rate of intrauterine infection in infants was significantly higher than those who were with both negative results (P < 0.05). Levels of HBV cccDNA and the rate of positive samples were significantly higher in mothers with infants who appeared to have had intrauterine infection than those did not (P < 0.01 and < 0.05, respectively). CONCLUSION: HBV infection could be discovered in the human ovary and might be transmitted to the filial generation via ovum.

Telbivudine prevents vertical transmission from HBeAg-positive women with chronic hepatitis B.

BACKGROUND & AIMS: Telbivudine reduces hepatitis B virus (HBV) DNA and normalizes levels of alanine aminotransferase (ALT) in patients with chronic hepatitis B (CHB). We investigated its use in preventing vertical transmission. METHODS: We performed an open-label, prospective study of 88 hepatitis B (HB) e antigen (HBeAg)-positive pregnant women with CHB, levels of HBV DNA >6 log(10) copies/mL, and increased levels of ALT. Women were given telbivudine (n = 53) starting in the 2nd or 3rd trimester, or no treatment (controls, n = 35) and followed until postpartum week (PPW) 28. All infants received standard immunoprophylaxis after birth. RESULTS: At 28 weeks, none of the infants whose mothers received telbivudine had immunoprophylaxis failure, whereas 8.6% of the infants of control mothers did (P = .029). There were no differences between groups in mothers' adverse events or infants' congenital deformities, gestational age, height, and weight, or Apgar scores. At postpartum week 28, significantly more telbivudine-treated mothers had levels of HBV DNA <500 copies/mL, normalized levels of ALT, and hepatitis B e antigen seroconversion compared with controls (58% vs none, P < .001; 92% vs 71%; P = .008; and 15% vs none; P < .001, respectively) but none had loss of hepatitis B surface antigen. Telbivudine-treated mothers had no virologic breakthrough (HBV DNA >1 log(10) increase from <500 copies/mL) or discontinuations from adverse events. After delivery, 13/52 patients discontinued telbivudine due to preference. There were no episodes of severe hepatitis (levels of ALT >10 times the upper limit of normal) in either group during 28 weeks of postpartum observation. CONCLUSIONS: Women with CHB given telbivudine during the second or third trimester of pregnancy have reduced rates of perinatal transmission. Telbivudine produced no adverse events in mothers or infants by 28 weeks.

A prospective and open-label study for the efficacy and safety of telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis B virus infection.

BACKGROUND & AIMS: In the Asia-Pacific region, perinatal transmission of the hepatitis B virus (HBV) is the primary cause of chronic hepatitis B infection. Despite the use of HBIG and HBV vaccination, HBV perinatal transmission (PT) occurs in 10-30% of infants born to highly viremic mothers. We evaluated the efficacy and safety of LTD use during late pregnancy in reducing HBV transmission in highly viremic HBeAg+mothers. METHODS: Two hundred and twenty-nine HBeAg+HBV DNA levels>1.0×10(7) copies/ml mothers received telbivudine 600 mg/day from week 20 to 32 of gestation (n=135) or served as untreated controls (n=94). All infants in both arms received 200 IU of HBIg within 12 h postpartum and recombinant HBV vaccine of 20 µg at 0, 1, and 6 months. HBsAg and HBV DNA results of infants at week 28 were used to determine perinatal transmission rate. All telbivudine treated subjects were registered in the Antiretroviral Pregnancy Registry. RESULTS: Telbivudine treatment was associated with a marked reduction in serum HBV DNA and hepatitis B e antigen (HBeAg) levels and normalization of elevated ALT levels before delivery. A striking decline of HBV DNA levels started from treatment onset to week 4, and sustained in a low level since week 12. Forty-four (33%) of the 135 telbivudine-treated mothers and none (0%) of the untreated controls had polymerase chain reaction-undetectable viremia (DNA<500 copies/ml) at delivery. Seven months after delivery, the incidence of perinatal transmission was lower in the infants that completed follow-up born to the telbivudine-treated mothers than to the controls (0% vs. 8%; p=0.002). HBV DNA levels were only detectable in HBsAg+infants. No significant differences in anti-HBs levels were observed during postnatal follow-up. No serious adverse events were noted in the telbivudine-treated mothers or their infants. CONCLUSIONS: Telbivudine used during pregnancy in CHB HBeAg+highly viremic mothers can safely reduce perinatal HBV transmission. Telbivudine was well-tolerated with no safety concerns in the telbivudine-treated mothers or their infants on short term follow up. These data support the use of telbivudine in this special population.

[Abstract efficacy of combined vaccine for the prevention of HBV transmission in highly viremic HBeAg+ mothers and the HBV markers' dynamic change of babies in follow-up].

OBJECTIVE: To evaluate the efficacy of combined vaccination with 200IU dose of HBIG and 20 µg of anti-HBV vaccine for the prevention of HBV vertical transmission in babies delivered by HBeAg + and highly viremic mothers and the HBV markers' dynamic changes in babies during follow-up. METHODS: HBeAg + mothers with HBV DNA ≥ to 1.0 × 6 log(10) copies/ml were enrolled and their babies were followed up until 12 months old. The infants received HBIG 200 IU IM in 24 hrs and on day 15, and 20 µg recombinant anti-HBV vaccine at 0, 1 and 6 months. The HBV markers and HBV DNA were tested at birth day, and 1, 7, 12 months after birth respectively. The vertical transmission rate at birth and intrauterine infection rate, the HBsAb positive rate and the HBV markers' dynamic changes during follow up were evaluated. RESULTS: (1) 29 out of 127 infants with HBsAg (+) at birth, 11 of which were HBV DNA (+), HBV perinatal transmission rate was 22.83%. 2 infants' HBsAg were positive at month 1 and became negative at month 7 and 10 infants were still HBsAg (+) and HBV DNA (+). HBV intrauterine infection rate was 7.87%. (2) The positive rate of HBeAg and HBcAb in uninfected infants were 96.58% and 98.29% respectively, which declined gradually to undetectable level after immunization. No infants were HBeAb (+). (3) Infants uninfected produced effective HBsAb after vaccination. The level of HBsAb elevated gradually, and the level of HBeAg decreased quickly even to undetectable. CONCLUSION: The combination vaccination of 200 IU HBIG with 20 µg recombinant anti-HBV vaccine in the Infants delivered by HBeAg (+) and highly viremic mothers reduced obviously the rate of perinatal transmission of HBV, enhanced largely the production of antibody against HBV surface antigen and dropped the maternal HBeAg and HBcAb in infants or even to negative.