Search

Objective Twin-Reversed Arterial Perfusion (TRAP) sequence is a rare complication of monochorionic multiple gestation. Conservative management should be considered if there is no poor prognostic factor. Case report This is a 35 year-old female with twin pregnancy with acardiac monster. Under the request of the patient, there was no intervention during the whole pregnancy. We keep regular and close sonography weekly follow up. There was no maternal complication and there was also no heart failure sign or polyhydramnios of the donor twin. Minimal blood flow was noted at the anastomotic vessels under the sonography at late gestational age. Due to breech presentation, cesarean section was performed at gestational age 37 + 1/7 weeks. She delivers a healthy baby smoothly. Conclusion Antenatal sonography is an important tool to evaluate the fetus status. Under special condition, term pregnancy is still possible without any treatment. Case report Twin reversed arterial perfusion syndrome in a monochorionic monoamniotic twin pregnancy.

Introduction: Prenatal depression (PND) is a common psychiatric disorder in pregnant women and leads to psychosocial dysfunction, high suicidal rate, and adverse childcare. Patients with PND have omega-3 polyunsaturated fatty acid (omega-3 or n-3 PUFAs) deficits, which might link to chronic low-grade inflammatory process and the pathophysiological mechanisms of depression. In this case-control study, we examined the levels of PUFAs and inflammatory cytokines in PND. Method: Blood samples were obtained and analyzed from 16 healthy controls and 17 depressed cases (PND group) diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Independent sample t-test and correlation analysis were performed with Statistical Package for the Social Sciences (SPSS) logistics correlation analysis. Results: PND group had significantly lower levels of total n-3 (p = 0.026), docosahexaenoic acid (DHA) (p = 0.020) and eicosapentaenoic (EPA) (p = 0.019) but a higher omega-6 (n-6)/n-3 PUFAs ratio (p = 0.007) and tumor necrosis factor alpha (TNF-α) (p = 0.016) level. Moreover, the duration of current PND episodes were also significantly correlated with DHA, EPA, n-3 PUFAs, n-6/n-3 ratio and TNF-α. In terms of PUFAs and cytokine levels, only DHA was inversely correlated with TNF-α. Conclusion: PND is significantly associated with lower DHA, EPA, and total n-3 PUFAs levels and an increased n-6/n-3 PUFAs ratio, while the duration of PND is associated with lower levels of n-3 PUFAs, including DHA and EPA. The correlation of PUFAs levels with depression and TNF-α level grant further investigation into the inflammatory process underlying PND, mediated by PUFAs.

Background Atherosclerosis is a chronic inflammatory disease of the vessel wall associated with oxidized low-density lipoprotein (oxLDL)-induced apoptosis of endothelial cells. Coenzyme Q10 (CoQ10), a potent antioxidant and a critical intermediate of the electron transport chain, has been reported to inhibit LDL oxidation and thus the progression of atherosclerosis. However, its molecular mechanisms on endothelial cells remain still unclarified. Methods In this study, primary human umbilical vein endothelial cell cultures treated with oxLDL were used to explore the protective effects of CoQ10. Results Our results showed that CoQ10 attenuated the oxLDL-induced generation of reactive oxygen species and improved the antioxidant capacity. CoQ10 also attenuated the oxLDL-mediated down-regulation of endothelial nitric oxide synthase (eNOS) and up-regulation of inducible nitric oxide synthase (iNOS). In addition, CoQ10 suppressed oxLDL-activated NF-κB and downstream inflammatory mediators, including expression of adhesion molecules, release of proinflammatory cytokines and the adherence of monocytic THP-1 cells. Moreover, CoQ10 attenuated oxLDL-altered proapoptotic responses. The inhibitor of eNOS ( l -NIO 10 μM) and iNOS (1400W 10 μM) as well as NO enhancer (SNP 10 μM) were used to clean up the mechanism. Conclusion These results provide new insight into the possible molecular mechanisms by which CoQ10 protects against atherogenesis by NO-related pathways.

Background This study evaluated the incidence, nature, and seriousness of adverse drug reactions (ADRs) occurring after AdimFlu-S® influenza A (H1N1) vaccination in pregnant women was administered. Methods This is a retrospective cohort study. Between October 2009 and February 2010, 198 pregnant women who had received the AdimFlu-S® influenza A (H1N1) vaccine during pregnancy and 198 age-matched pregnant women who had not received influenza vaccine were included and recorded. The pregnancy outcome and maternal adverse effects were extracted from chart reviews. Infant health status data were followed up until 8 weeks post-partum. Results During the observation period of each cohort, four subjects (2.0%) in the exposed group experienced vaccine-related adverse events that were mild in severity. A total of 17 women (8.6%) in the vaccine exposed group and 40 women (20.2%) in the unexposed group underwent at least one adverse effect during their pregnancy. A total of 72 infants (35.6%) in the exposed group and 101 infants (49%) in the unexposed group had at least one adverse event within 8 weeks after they were born (p

Severe steroid-resistant acute graft-versus-host disease (aGVHD) is associated with high mortality. Bone marrow-derived mesenchymal stem cells (BMMSC) have been found to be immunosuppressive, and intravenous infusion of BMMSC is an effective therapy for steroid-resistant aGVHD. However, acquiring BMMSC requires an invasive procedure.We compared umbilical cord-derived mesenchymal stem cells (UCMSC) and BMMSC for morphology, surface markers expression, differentiation, proliferative potential, and their suppressive effects on peripheral blood mononuclear cell proliferation. After institutional review board approved, we intravenously infused ex vivo expanded third-party UCMSC into two patients with severe steroid-resistant aGVHD. Adverse effects and patient responses of UCMSC were monitored. All procedures for UCMSC processing complied with current good tissue practice requirements.We found that UCMSC had superior proliferative potential and more suppressive effects on peripheral blood mononuclear cell proliferation compared with BMMSC. The aGVHD improved dramatically after each of four infusions of UCMSC into the two patients. No adverse effects were noted. Both patients are doing well now. CONCLUSIONS. Considering that acquiring UCMSC is noninvasive, these cells would appear to be the ideal candidates for clinical cell-based therapies. This is the first report of UCMSC in a human clinical application, and this procedure seems both feasible and safe. These findings suggested that UCMSC were effective for treating aGVHD.

The authors report a case of congenital hepatoblastoma that was diagnosed in the antenatal period at 39 weeks' gestation. The infant was delivered vaginally without rupture of the tumor. The neonate then received chemotherapy and underwent surgical excision of the tumor. After 1 year, no tumor recurrence has been noted.

Endothelial apoptosis is a driving force in atherosclerosis development. Oxidized low-density lipoprotein (oxLDL) promotes inflammatory and thrombotic processes and is highly atherogenic, as it stimulates macrophage cholesterol accumulation and foam cell formation. Previous studies have shown that the phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase/nitric oxide (PI3K/Akt/eNOS/NO) pathway is involved in oxLDL-induced endothelial apoptosis. Ellagic acid, a natural polyphenol found in berries and nuts, has in recent years been the subject of intense research within the fields of cancer and inflammation. However, its protective effects against oxLDL-induced injury in vascular endothelial cells have not been clarified. In the present study, we investigated the anti-apoptotic effect of ellagic acid in human umbilical vein endothelial cells (HUVECs) exposed to oxLDL and explored the possible mechanisms. Our results showed that pretreatment with ellagic acid (5-20μM) significantly attenuated oxLDL-induced cytotoxicity, apoptotic features, and generation of reactive oxygen species (ROS). In addition, the anti-apoptotic effect of ellagic acid was partially inhibited by a PI3K inhibitor (wortmannin) and a specific eNOS inhibitor (cavtratin) but not by an ERK inhibitor (PD98059). In exploring the underlying mechanisms of ellagic acid action, we found that oxLDL decreased Akt and eNOS phosphorylation, which in turn activated NF-κB and downstream pro-apoptotic signaling events including calcium accumulation, destabilization of mitochondrial permeability, and disruption of the balance between pro- and anti-apoptotic Bcl-2 proteins. Those alterations induced by oxLDL, however, were attenuated by pretreatment with ellagic acid. The inhibition of oxLDL-induced endothelial apoptosis by ellagic acid is due at least in part to its anti-oxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway.

Flavonoids are polyphenolic compounds found in various foods of plants. Rutin, one of the flavonoids, had been showed induced apoptosis in cancer cells. There is no available information to address rutin affects murine leukemia cells in vivo. In the present study, we are focused on the in vivo effects of rutin on leukemia WEHI-3 cells. The effects of rutin on WEHI-3 in BALB/c mice in vivo were also examined and the results indicated that rutin decreased the percentage of Mac-3 marker, indicating that the differentiation of the precursor of macrophage and T cells was inhibited. The weights of liver and spleen were decreased from rutin-treated groups compared to the control groups and the results indicated that rutin decreased the weight of these organs. One of the major characteristic of WEHI-3 leukemia is the enlarged spleen in murine after i.p. injection of WEHI-3 cells. After the pathological examination, the function of rutin was observed in the liver and spleen in the mice previously injected with WEHI-3 cells. Rutin promoted the activity of macrophage phagocytosis in cells which isolated from peritoneal (i.p.). Taken together, rutin can affect WEHI-3 cells in vivo.

Background: Perinatal depression is common, and treatment remains challenging. Depression has been reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs). A profound decrease of omega-3 PUFAs in the mother during pregnancy is associated with the higher demand of fetal development and might precipitate the occurrence of depression. In this study, we examined the efficacy of omega-3 PUFA monotherapy for the treatment of depression during pregnancy.

Objective This study is to examine the effect of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 taken orally before bedtime on Group B Streptococcus (GBS)-positive pregnant women with respect to becoming GBS negative. Materials and Methods In total, 110 pregnant women at 35–37 weeks of gestation who were diagnosed by GBS culture as being GBS positive for both vaginal and rectal GBS colonization were randomly assigned to be orally treated with two placebo capsules or two probiotic capsules (containing L. rhamnosus GR-1 and L. reuteri RC-14) before bedtime until delivery. All women were tested for vaginal and rectal GBS colonization again by GBS culture on admission for delivery. Results Of the 110 participants, 99 completed the study (49 in the probiotic group and 50 in the placebo group). The GBS colonization results changed from positive to negative in 21 women in the probiotic group (42.9%) and in nine women in the placebo group (18.0%) during this period (Chi-square p =0.007). Conclusion Oral probiotic containing L. rhamnosus GR-1 and L. reuteri RC-14 could reduce the vaginal and rectal GBS colonization rate in pregnant women.

Summary Objective Fetal tachyarrhythmia may cause fetal hydrops and lead to fetal morbidity and mortality. Supraventricular tachycardia and atrial flutter have been the most diagnosed. We present a case of fetal atrial flutter diagnosed during the second trimester treated with digoxin and sotalol and delivered at term. Case Report A 30-year-old primigravid woman was diagnosed with fetal atrial flutter at the gestational age of 25 weeks with atrial rates of 480-520 bpm and ventricular rates of 200-250 bpm. Initially, she was treated with digoxin then with a combination of digoxin and sotalol. The fetal heart beat slowed after sotalol treatment but did not return to sinus rhythm. The fetus was delivered vaginally. Neonatal echocardiography showed a small apical ventricular septal defect and small patent ductus arteriosus. Electrocardiography also revealed atrial flutter with occasional atrial fibrillation. Conclusion The efficacy of antiarrhythmic drug therapy for fetal atrial flutter has not been well established. In our case, we used sotalol combined with digoxin and the fetal heart beat slowed after therapy. Sotalol may be considered the drug of choice for fetal atrial flutter. If the fetal atrial flutter is resistant to these therapies, a combination of other congenital cardiac diseases or organic abnormalities should be considered.

Uterine leiomyomas are the most common benign uterine tumors in the women of reproductive age. Previous studies have suggested that uterine leiomyomas are monoclonal tumors derived from a single neoplastic myometrial cell. However, the neoplastic transformation of myometrium to leiomyomas remains to be elucidated. The classical cadherins are a gene family of integral membrane glycoproteins that mediate calcium-dependent cell-cell adhesion in a homophilic manner. These cell adhesion molecules (CAMs) have been shown to play pivotal roles in tumorigenesis. Catenins are intracellular proteins that link the cytoplasmic domains of the cadherins to the cytoskeletons to promote the biological functions of these CAMs. In this study, we compared the expression of E-, N-, and P-cadherins and alpha-, beta-, and gamma-catenins in the uterine leiomyomas and the counterparts of normal myometrium of the same patients by using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Of these, E-cadherin (E-cad) was not detected in both uterine leiomyomas and myometrium, P-cadherin (P-cad) was similarly expressed in these two tissues, but N-cadherin (N-cad) mRNA and protein expression levels in uterine leiomyomas were significantly greater than those observed in the myometrium. Catenins were not differentially expressed in uterine myometrium and leiomyomas. The overexpression of N-cad in uterine leiomyomas suggests that this CAM may play a central role in the development of uterine leiomyomas.

Three cases of primary hyperparathyroidism in pregnancy are described. Patient 1 developed left thigh pain and lower abdominal pain at 34 weeks' gestation. Patient 2 had right flank pain and lower abdominal pain at 32 weeks' gestation. Both patients accepted medical therapy initially, which resulted in poor control of hypercalcemia. Patient 1 delayed her parathyroidectomy until the postpartum period; she had maternal hypercalcemia and neonatal hypocalcemia. Patient 2 accepted parathyroidectomy at 32 weeks' gestation with an uneventful outcome for both mother and baby. Patient 3 was asymptomatic; her hyperparathyroidism was diagnosed postpartum after neonatal hypocalcemia and agreed to parathyroidectomy. All 3 patients had a parathyroid adenoma.

In this present study we investigated the effects of a saponin fraction prepared from the roots of Panax notoginseng (Burt.) F. H. Chen (Family Araliaceae), on human sperm motility and progression in vitro. Fifteeen human semen samples were collected and qualified according to the criteria of W.H.O. The saponin fraction was evaluated at 1.0 mg/ml and 2.0 mg/ml respectively. The results demonstrate that the fraction increased motility as well as progression of sperm at the 60(th) minute or the 120(th) minute.

Diallyl sulfide (DAS) is a component of garlic (Alliaceae family). Although diallyl polysulfide has been shown to exhibit anticancer activities, no report explored DAS-affected cell death in human cervical cancer cells in vitro. This study investigated DAS affected on cell-cycle regulation and apoptosis in human cervical cancer Ca Ski cells. DAS at 25-100 μM decreased the viability of Ca Ski cells by increasing G0/G1 phase arrest followed by induction of apoptosis in concentration- and time-dependent effects. Flow cytomteric assay indicated that DAS (75 μM) promoted the production of Ca(2+) accumulation and decreased the level of mitochondrial membrane potential in Ca Ski cells. Western blotting showed that 75 μM of DAS-induced G0/G1 phase arrest was mediated through the increased expression of p21, p27, and p53 with a simultaneous decrease in CDK2, CDK6, and CHK2 expression. The characteristics of apoptosis, such as morphological changes and DNA condensation, altered the ratio of Bax/Bcl-2 and sub-G1 phase occurred in Ca Ski cells after exposure to DAS. Furthermore, DAS induced mitochondrial dysfunction, leading to the release of cytochrome c for causing apoptosis in Ca Ski cells. These findings suggest that DAS might be a potential chemotherapeutic agent for the treatment of cervical cancer.

Objective Amniotic fluid embolism syndrome is a fatal disease in pregnant women. The exact role of platelets and neutrophils in amniotic fluid embolism syndrome is not clear. We examined whether amniotic fluid could affect platelet-neutrophil aggregation and activation and the possible mechanisms. Study Design Blood samples from the pregnant women were pretreated ex vivo with their own amniotic fluid. Flow cytometry was used to measure platelet-neutrophil aggregation and activation. Neutrophil-mediated activity of p38 mitogen-activated protein kinase and extracellular signal-regulated protein kinases 1 and 2 was analyzed by Western blotting. Results Amniotic fluid significantly induced platelet-neutrophil aggregation, neutrophil CD11b expression, and reactive oxygen species production. Amniotic fluid induced minimal platelet P-selectin expression. The increase of intracellular calcium level of neutrophils and the activity of p38 mitogen–activated protein kinase were enhanced by amniotic fluid stimulation. Conclusion Amniotic fluid was able to induce neutrophil activation and platelet-neutrophil aggregation with minimal effect on platelet activation. These findings may provide a new insight in the understanding of the pathophysiologic condition of amniotic fluid embolism syndrome.

Vinorelbine tartrate (VNR), a semi-synthetic vinca alkaloid acquired from vinblastine, has extensively been used as an anticancer agent. However, VNR-induced oxidative damage may cause several side effects, such as venous irritation, vascular pain, and necrotizing vasculitis, thereby repressing clinical treatment efficiency. The molecular mechanisms underlying the induced oxidative stress in endothelial cells are still largely unknown. This study was designed to test the hypothesis that VNR induces oxidative injury through modulation of AMP-activated protein kinase (AMPK) and possible mechanisms were then explored. Human umbilical vein endothelial cells (HUVECs) were treated with VNR (5–0.625 μM) to produce oxidative damage. The VNR-mediated AMPK, PKC, and NADPH oxidase expressions were investigated by western blotting. Furthermore, several oxidative stress-induced oxidative damage markers as well as pro-inflammatory responses were also investigated. VNR treatment resulted in dephosphorylation of AMPK, which in turn led to an activation of NADPH oxidase by PKC; however, the phenomena were repressed by AICAR (an agonist of AMPK). Furthermore, VNR suppressed Akt/eNOS and enhanced p38 mitogen-activated protein kinase (MAPK), which in turn activated the NF-κB pathway. Furthermore, VNR facilitated several pro-inflammatory events, such as the adherence of monocytic THP-1 cells to HUVECs, pro-inflammatory cytokines release, and overexpression of adhesion molecular. Our results highlight a possible molecular mechanism for VNR-mediated endothelial dysfunction.

Danthron has been shown to induce apoptotic cell death, and inhibit migration and invasion of human gastric or brain cancer cells in vitro. However, there is no report addressing whether danthron affects murine leukemia cells or immune responses in vivo. Herein, this study focused on the in-vivo effects of danthron on WEHI-3 leukemia in mice and immune responses in vivo. The results indicated that danthron reduced spleen weight and increased the percentage of cells with CD3 and CD19 markers, indicating that differentiation of the precursors of T- and B-cells was promoted in the leukemic mice. The results also showed that danthron promoted the activity of phagocytosis by macrophages isolated from the peritoneal cavity but had no effect on peripheral blood mononuclear cells. Danthron also promoted natural killer cell cytocytic activity at an effector and target cell ratio of 100:1 in comparison with leukemic animals in vivo. Taken together, these results demonstrated that application of danthron might affect WEHI-3 leukemia in mice and modulate immune responses in vivo.

Previous studies have shown that vascular endothelium-derived matrix metalloproteinases (MMPs) contribute to the destabilization of atherosclerotic plaques, a key event triggering acute myocardial infarction. In addition, studies have reported that the PKC-MEK-PPARγ signaling pathway is involved in oxidized low-density lipoprotein (oxLDL)-induced expression of MMPs. Ellagic acid, a phenolic compound found in fruits and nuts, has potent antioxidant, anti-inflammatory, and anticancerous properties. However, the molecular mechanisms underlying its antiatherogenic effects remain to be clarified. This study aimed to assess whether the effects of ellagic acid on the fibrotic markers MMP-1 and MMP-3 are modulated by the PKC-ERK-PPAR-γ signaling pathway in human umbilical vein endothelial cells (HUVECs) that have been exposed to oxLDL. It was found that ellagic acid significantly inhibited oxLDL-induced expressions of MMP-1 and MMP-3. Pretreatment with ellagic acid and DPI, a well-known ROS inhibitor, attenuated the oxLDL-induced expression and activity of PKC-α. In addition, ellagic acid as well as pharmacological inhibitors of ROS, calcium, and PKC strongly suppressed the oxLDL-induced phosphorylation of extracellular signal-regulated kinase (ERK) and NF-κB activation. Moreover, ellagic acid ameliorated the oxLDL-induced suppression of PPAR-γ expression. In conclusion, the data suggest that ellagic acid elicits its protective effects by modulating the PKC-α/ERK/PPAR-γ/NF-κB pathway, resulting in the suppression of ROS generation and, ultimately, inhibition of MMP-1 and MMP-3 expression in HUVECs exposed to oxLDL.

Scope: The lectin-like oxidized low-density lipoprotein receptor (LOX-1) is one pivot receptor for oxidized low-density lipoprotein (oxLDL) in human endothelial cells. Co-enzyme Q10 (Co Q10) has been widely used in clinical intervention. However, the molecular mechanisms underlying its protective effects against oxidative stress in endothelial cells are still largely unknown. This study was designed to test the hypothesis that Co Q10 mitigates oxLDL-induced endothelial oxidative injuries via modulation of LOX-1-mediated reactive oxygen species (ROS) generation and explored the role of AMP-activated protein kinase (AMPK), a negative regulator of NADPH oxidase. Methods and results: Human umbilical vein endothelial cells (HUVECs) were pretreated with Co Q10 and then incubated with oxLDL for 24 h. Co Q10 attenuated oxLDL-elicited LOX-1 expression and ROS generation by suppression of NADPH oxidase activation. Co Q10 rescued dephosphorylation of AMPK caused by oxLDL that in turn led to an activation of NADPH oxidase by PKC. The results were confirmed using AMPK siRNA. Moreover, oxLDL-suppressed Akt/eNOS and enhanced p38 phosphorylation, which in turn activated NF-κB pathway. These detrimental events were ameliorated by Co Q10. Conclusion: These results provide new highlight onto the possible molecular mechanisms of how Q10 suppresses oxLDL-induced endothelial oxidative injuries by the modulation of LOX-1-mediated ROS generation via the AMPK/PKC/NADPH oxidase signaling pathway.

It is well known that the response of cancer cells to chemotherapeutic drugs involves the activation of apoptotic pathways. Benzyl isothiocyanate (BITC) is an important compound found in plant food and has been shown to have anti-cancer effects on human cancer cells, but its effect on prostate cancer cells in vitro remains unknown. The aim of the present study was to investigate the effects of BITC on DU 145 human prostate cancer cells in order to clarify whether a time/concentration range for optimal BITC-induced apoptosis exists and to find the associated signaling pathway. Cell morphological changes, percentage of cell viability, DNA damage and apoptosis in DU 145 cells were examined by phase-contrast microscopy, flow cytometric assay, 4',6-diamidine-20-phenylindole dihydrochloride staining, comet assay and Western blotting analysis. The results indicate that BITC induces cell morphological changes, decreases the percentage of viable cells (induction of cell cytotoxicity), and induces DNA damage and apoptosis in DU 145 cells in a time- and dose-dependent manner. Flow cytometric assays indicated that BITC promoted reactive oxygen species and Ca2+ productions and decreased the levels of mitochondrial membrane potential (ΤYm), while the pre-treatment with N-acetylcysteine caused an increase in the percentage of viable cells. BITC also promoted caspase-3, -8 and -9 activities. Furthermore, when cells were pre-treated with the caspase-3 inhibitor and then treated with BITC, this led to an increase in the percentage of viable cells. Confocal laser microscopy examination indicated that BITC promoted the expression of AIF and Endo G, which were released from the mitochondria in DU 145 cells. In conclusion, BITC induces apoptosis in DU 145 cells through the release of AIF and Endo G from the mitochondria and also promotes caspase-3 activation.

20-Fluoro-6,7-methylenedioxy-2-phenyl-4-quino-lone (CHM-1) has been reported to induce cell cycle arrest and apoptosis in many types of cancer cells. However, there is no available information to show CHM-1 affecting DNA damage and expression of associated repair genes. Herein, we investigated whether or not CHM-1 induced DNA damage and affected DNA repair gene expression in U-2 OS human osterogenic sarcoma cells. The comet assay showed that incubation of U-2 OS cells with 0, 0.75, 1.5, 3 and 6 μM of CHM-1 led to a longer DNA migration smear (comet tail). DNA gel electrophoresis showed that 3 μM of CHM-1 for 24 and 48 h treatment induced DNA fragmentation in U-2 OS cells. Real-time PCR analysis showed that treatment with 3 μM of CHM-1 for 24 h reduced the mRNA expression levels of ataxia telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR), breast cancer 1, early onset (BRCA1), 14-3-3sigma (14-3-3σ), DNA-dependent serine/threonine protein kinase (DNA-PK) and O(6)-methylguanine-DNA methyltransferase (MGMT) genes in a time-dependent manner. Taken together, the results indicate that CHM-1 caused DNA damage and reduced DNA repair genes in U-2 OS cells, which may be the mechanism for CHM-1-inhibited cell growth and induction of apoptosis.

Our earlier studies showed that DATS induced apoptosis in human colon cancer HT29 and colo 205 cell lines in vitro. However, there is no report to show that DATS induced apoptosis in vitro and inhibited CT26 cancer cells in vivo on a murine allograft animal model. In vitro studies, the results indicated that DATS induced morphological changes and induction of apoptosis in CT26 cells. In vivo studies, CT26 cancer cells were implanted into BALB/c mice and groups of mice were treated with vehicle, DATS (10 and 50 mg/kg of body weight). DATS were injected once per four days intraperitoneally (i.p.), with treatment starting 4 weeks prior to cells inoculation. Treatment with vehicle or with 10 and 50 mg/kg of DATS resulted in a reduction in tumor volume and weight. Tumor volume and total hemoglobin in allograft mice treated with 50 mg/kg DATS were significantly smaller than that in the control group. These findings indicated that DATS inhibits tumor growth in an allograft animal model. Thus, DATS may represent a colon cancer preventive agent and can be used in the future.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), originally identified as the major receptor for oxidized low-density lipoprotein (oxLDL) in endothelial cells, plays a major role in the pathology of vascular diseases. Green tea consumption is associated with reduced cardiovascular mortality in some epidemiological studies. In the present study, we hypothesized that the most abundant polyphenolic compound in tea, epigallocatechin-3-gallate (EGCG), can downregulate parameters of endothelial dysfunction by modulating LOX-1-regulated cell signaling. In cultured human umbilical vein endothelial cells (HUVECs), exposure to oxLDL (130 μg/ml), which led to an increase in LOX-1 expression at the RNA and protein levels, was abrogated by addition of EGCG or DPI, a well-known inhibitor of flavoproteins, suggesting the involvement of NADPH oxidase. Furthermore, oxLDL rapidly activated the membrane translocation of Rac-1 and p47phoxand the subsequent induction of ROS generation, which was suppressed markedly by pretreatment with EGCG or anti-LOX-1 monoclonal antibody. OxLDL also increased p38 MAPK phosphorylation and decreased phosphorylation of the amino-terminal region of Akt, with maximal induction at about 30 min, and NF-κB phosphorylation within 1 h, resulting in redox-sensitive signaling. In addition, oxLDL diminished the expression of endothelial nitric oxide synthase (eNOS), enhanced the expression of endothelin-1 and adhesion molecules (ICAM, E-selectin, and monocyte chemoattractant protein-1), and increased the adherence of monocytic THP-1 cells to HUVECs. Pretreatment with EGCG, however, exerted significant cytoprotective effects in all events. These data suggest that EGCG inhibits the oxLDL-induced LOX-1-mediated signaling pathway, at least in part, by inhibiting NADPH oxidase and consequent ROS-enhanced LOX-1 expression, which contributes to further ROS generation and the subsequent activation of NF-κB via the p38 MAPK pathway. Results from this study may provide insight into a possible molecular mechanism by which EGCG suppresses oxLDL-mediated vascular endothelial dysfunction.

Aloe-emodin, one of the anthraquinones, has been shown to have anticancer activity in different kinds of human cancer cell lines. Therefore, the purpose of this study was to investigate the anti-cancer effect of aloe-emodin on human tongue squamous carcinoma SCC-4 cells. The results indicated that aloe-emodin induced cell death through S-phase arrest and apoptosis in a dose- and time-dependent manner. Treatment with 30 microM of aloe-emodin led to S-phase arrest through promoted p53, p21 and p27, but inhibited cyclin A, E, thymidylate synthase and Cdc25A levels. Aloe-emodin promoted the release of apoptosis-inducing factor (AIF), endonuclease G (Endo G), pro-caspase-9 and cytochrome c from the mitochondria via a loss of the mitochondrial membrane potential (DeltaPsi(m)) which was associated with a increase in the ratio of B-cell lymphoma 2-associated X protein (Bax)/B cell lymphoma/leukemia-2 (Bcl-2) and activation of caspase-9 and -3. The free radical scavenger N-acetylcysteine (NAC) and caspase inhibitors markedly blocked aloe-emodin-induced apoptosis. Aloe-emodin thus induced apoptosis in the SCC-4 cells through the Fas/death-receptor, mitochondria and caspase cascade. Aloe-emodin could be a novel chemotherapeutic drug candidate for the treatment of human tongue squamous cancer in the future.

Prenatal genetic diagnosis plays an important role in eugenics. Early detection of embryo and fetus abnormalities allows preventive precautions to be taken and treatment to begin early in order to reduce the severity and extent of congenital deformities. Advancements in genetic diagnostic techniques infer that nurses are increasingly likely to deal with prenatal genetic diagnosis cases. This essay introduces a few prevalent prenatal genetic diagnosis methods used at different stages of pregnancy; describes in a comprehensive manner the potential physical and psychological responses of the client; and introduces principles of administering prenatal genetic diagnosis to healthcare clients. Ethical issues related to prenatal genetic diagnosis are also discussed.

Post-operation pain is a very subjective phenomenon. The aim of this study was to find out the effects of acupuncture or electro-acupuncture on post-cesarean pain.Sixty women, who had had spinal anesthesia during cesarean section at the Department of Obstetrics of China Medical University Hospital, were randomly assigned to the control group, the acupuncture group, and the electro-acupuncture group. After the operation, we applied subjects with acupuncture or electro-acupuncture on the bilateral acupuncture point, San Yin Jiao (Sp6), and the patient controlled analgesia (PCA). The first time of requesting morphine, the frequency of PCA demands in 24 hours, and the doses of PCA used were recorded double blindly. In addition, monitoring the subjects' vital signs, the opioid-related side effects, and the pain scores was done.The results showed that the acupuncture group and the electro-acupuncture group could delay the time of requesting morphine up to 10 - 11 minutes when compared with the control group. The total dose of PCA used within the first 24 hours was 30% - 35% less in the acupuncture group and the electro-acupuncture group when compared with the control group, which was indicated in statistical significance. However, there was no significant difference between the acupuncture group and the electro-acupuncture group. The electro-acupuncture group's and the acupuncture group's pain scores were lower than the control group's within the first 2 hours. Both were statistically significant. However, two hours later, there were no significant differences of the visual analogue scale (VAS) scores between either of the treatment groups and the control group. Finally, the incidence of opioid-related side effects, such as dizziness, was less in the acupuncture group and electro-acupuncture group than in the control group.This study shows that the application of acupuncture and electro-acupuncture could definitely delay the time of requesting pain relief medication after cesarean section and decrease the PCA doses used within the first 24 hours.

Gallic acid is a polyhydroxyphenolic compound which can be found in various natural products. It is recognized to be an excellent free radical scavenger and has been shown to induce apoptosis in lung cancer and leukemia cells. No report has addressed whether gallic acid affects mouse leukemia cells in vivo. In this study, we examined the in vivo effects of gallic acid on leukemia WEHI-3 cells and on macrophage phagocytosis. Gallic acid caused a significant decrease in the weights of the spleens and livers from BALB/c mice. One of the major characteristic of WEHI-3 leukemia is the enlarged spleen in mice after i.p. injection of WEHI-3 cells. Gallic acid did not affect the percentages of CD3, CD11 and CD19 markers but decreased the percentage of Mac-3 in a high-dose (80 mg/kg) treatment while promoting Mac-3 levels in a low-dose (40 mg/kg) treatment. Gallic acid promoted the activity of macrophage phagocytosis in the white blood cells from peripheral blood mononuclear cells (PBMCs) at 40 and 80 mg/kg treatment doses, but decreased the macrophage phagocytosis in isolated peritoneal cells at the 80 mg/kg dose.

The cytotoxicity of berberine on C6 rat glioma cells indicated that berberine induced morphological changes and caused cell death through G2/M arrest and apoptosis. While undergoing apoptosis, there was a remarkable accumulation of G2/M cells with the upregulatoin of Wee1 but it also inhibited cyclin B, CDK1 and Cdc25c that led to G2/M arrest. Along with cytotoxicity in C6 cells, several apoptotic events including mitochondrial cytochrome c release, activation of caspase-9, -3 and -8 and DNA fragmentation were induced. Berberine increased the levels of GADD153 and GRP 78 in C6 cells based on the examination of Western blotting and this is a major hallmark of endoplasmic reticulum (ER) stress. We also found that berberine promoted the production of reactive oxygen species and Ca2+ in C6 cells. Western blotting assay also showed that berberine inhibited the levels of anti-apoptotic protein Bcl-2 but increased the levels of pro-apoptotic protein Bax before leading to a decrease in the levels of mitochondrial membrane potential (DeltaPsim) followed by cytochrome c release that caused the activations of capase-9 and -3 for apoptotic occurrence. The caspase-8, -9 and -3 were activated by berberine in C6 cells based on the substrate solution (PhiPhiLux-G1D1, CaspaLux 8-L1D2, CaspaLux 9-M1D2 for caspase-3, -8 and -9, respectively) and analyzed by flow cytometer and each inhibitor of caspase-8, -9 and -3 led to increase the percentage of viable C6 cells after exposure to berberine. This finding was also confirmed by Western blot assay which showed that berberine promoted the active form of caspase-8, -9 and -3. These results demonstrate that the cytotoxicity of berberine in C6 rat glioma cells is attributable to apoptosis mainly through induced G2/M-arrested cells, in an ER-dependent manner, via a mitochondria-dependent caspase pathway regulated by Bax and Bcl-2.

Although rhein has been shown to induce apoptosis in several cancer cell lines, the mechanism of action of rhein-induced cell cycle arrest and apoptosis at the molecular level is not well known. In this study, the mechanism of rhein action on A-549 human lung cancer cells was investigated. Rhein induced G0/G1 arrest through inhibition of cyclin D3, Cdk4 and Cdk6. The efficacious induction of apoptosis was observed at 50 microM for 12 h and up to 72 h as examined by a flow cytometric method. Flow cytometric analysis demonstrated that rhein increased the levels of GADD153 and GRP78, both hallmarks of endoplasmic reticulum stress, promoted ROS and Ca2+ production, induced the loss of mitochondrial membrane potential (delta psi(m)), promoted cytochrome c release from mitochondria, promoted capase-3 activation and led to apoptosis. Rhein also increased the levels of p53, p21 and Bax but reduced the level of Bcl-2. The Ca2+ chelator BAPTA was added to the cells before rhein treatment, thus blocking the Ca2+ production and inhibiting rhein-induced apoptosis in A-549 cells. Our data demonstrate that rhein induces apoptosis in A-549 cells via a Ca2+ -dependent mitochondrial pathway.

Atherosclerosis is a chronic inflammatory process with increased oxidative stress in vascular endothelium. Ginkgo biloba extract (GbE), extracted from Ginkgo biloba leaves, has commonly been used as a therapeutic agent for cardiovascular and neurological disorders. The aim of this study was to investigate how GbE protects vascular endothelial cells against the proatherosclerotic stressor oxidized low-density lipoprotein (oxLDL) in vitro. Human umbilical vein endothelial cells (HUVECs) were incubated with GbE (12.5–100 μg/ml) for 2 h and then incubated with oxLDL (150 μg/ml) for an additional 24 h. Subsequently, reactive oxygen species (ROS) generation, antioxidant enzyme activities, adhesion to monocytes, cell morphology, viability, and several apoptotic indexes were assessed. Our data show that ROS generation is an upstream signal in oxLDL-treated HUVECs. Cu,Zn-SOD, but not Mn-SOD, was inactivated by oxLDL. In addition, oxLDL diminished expression of endothelial NO synthase and enhanced expression of adhesion molecules (ICAM, VCAM, and E-selectin) and the adherence of monocytic THP-1 cells to HUVECs. Furthermore, oxLDL increased intracellular calcium, disturbed the balance of Bcl-2 family proteins, destabilized mitochondrial membrane potential, and triggered subsequent cytochrome c release into the cytosol and activation of caspase-3. These detrimental effects were ameliorated dose dependently by GbE ( P < 0.05). Results from this study may provide insight into a possible molecular mechanism underlying GbE suppression of the oxLDL-mediated vascular endothelial dysfunction.

Curcumin (diferuloylmethane), a phenolic compound from the plant Curcuma longa (Linn.) has been shown to exhibit antitumor activity and apoptosis in many human cancer cell lines including that of lung and liver cancer. In this study, curcumin was evaluated in BALB/c mice for its ability to inhibit pulmonary and liver adenoma formation and growth after they were orally treated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Animals were treated with DHPN in water for approximately 14 days before multiple doses of curcumin were given intraperitoneally. It was found that 200 microM curcumin reduced lung and liver tumor multiplicity by 37% (p0.05) and 30% (p0.05) respectively. The results indicated that curcumin significantly inhibited pulmonary and liver adenoma formation and growth in BALB/c mice. The precise mechanism by which curcumin inhibits lung and liver tumorigenesis remains to be elucidated. Thus, curcumin appears to be a promising new chemotherapeutic and preventive agent for lung and liver cancer induced by DHPN.

The effects of oral luteolin on the N-acetylation and metabolism of 2-aminofluorene (AF) in vivo were investigated in bladder, blood, colon, kidney, liver, feces, urine, cerebrum, cerebellum and pineal gland from male Sprague-Dawley rats. Major metabolites such as AAF, 1-OH-AAF, 3-OH-AAF, 8-OH-AAF and 9-OH-AAF were found in bladder tissues; AAF, 1-OH-AAF, 5-OH-AAF and 8-OH-AAF were found in blood samples; AAF, 1-OH-AAF, 3-OH-AAF, 5-OH-AAF, 8-OH-AAF and 9-OH-AAF were found in colon tissues; AAF, 1-OH-AAF, 3-OH-AAF and 9-OH-AAF were found in kidney tissues; AAF, 1-OH-AAF, 3-OH-AAF and 8-OH-AAF were found in liver tissues, AAF, 1-OH-AAF, 3-OH-AAF, 5-OH-AAF, 7-OH-AAF, 8-OH-AA and 9-OH-AAF were found in feces and urine samples; AAF, 1-OH-AAF, 3-OH-AAF and 8-OH-AAF were found in cerebrum tissues; AAF, 1-OH-AAF, 3-OH-AAF and 7-OH-AAF were found in cerebellum tissues; but only AF and AAF were found in pineal gland in rats treated with AF (50 mg/kg) for 24 h. Pretreatment of rats with luteolin (30 mg/kg) 24 h prior to the administration of AF (50 mg/kg) and luteolin given with AF concomitantly led to a decrease in the amounts of 3-OH-AAF and 9-OH-AAF and an increase in the amounts of 1-OH-AAF and 8-OH-AAF in bladder tissues. In blood samples, there were significant decreases of AAF, 1-OH-AAF and 8-OH-AAF after rats were treated with luteolin for 24 h prior to AF but luteolin with AF at the same time caused an increase in 1-OH-AAF. In colon tissues, there were significant decreases of AF, 1-OH-AAF, 3-OH-AAF, 5-OH-AAF and 9-OH-AAF after rats were treated with luteolin for 24 h then AF but the amounts of AF, 1-OH-AAF, 5-OH-AAF and 9-OH-AAF decreased and AAF and 8-OH-AAF increased in rats treated with luteolin and AF at the same time. In kidney tissues, there were significant decreases of AF, AAF and 3-OH-AAF after rats were treated with both compounds at the same time, but luteolin for 24 h then AF treatment led to significant decreases of 3-OH-AAF. In liver samples, after rats were treated with luteolin and AF at the same time, the amounts of AAF and 1-OH-AAF significantly decreased but 8-OH-AAF increased. However, rats treated with luteolin for 24 h then with AF led to significant decreases of AAF, 1-OH-AAF and 3-OH-AAF. In feces samples, there were significant increases of AAF, 3-OH-AAF, 7-OH-AAF, 8-OH-AAF and 9-OH-AAF after rats were treated with both compounds at the same time but luteolin for 24 h then AF treatment led to a significant increase of AF, 1-OH-AAF and 8-OH-AAF and a decrease AAF and 3-OH-AAF. In urine samples, there were significant increases of AF, AAF, 1-OH-AAF, 3-OH-AAF, 5-OH-AAF and 9-OH-AAF but a decrease of 8-OH-AAF after rats were treated with both compounds at the same time. However, the luteolin for 24 h then AF treatment led to significant increases of AF, AAF and 1-OH-AAF but decreases of 3-OH-AAF and 5-OH-AAF. In cerebrum samples, there were significant increases ofAF but decreases of 1-OH-AAF and 8-OH-AAF after rats were treated with both compounds at the same time; luteolin for 24 h then AF treatment of rats led to significant increase of 1-OH-AAF and decreases AF, AAF and 8-OH-AAF. In cerebellum samples, there were significant increases of AAF and decreases of 1-OH-AAF and 3-OH-AAF after rats were treated with both compounds at the same time, there is a significant increase of AAF but decrease of 1-OH-AAF, 3-OH-AAF and 7-OH-AAF after the luteolin treated for 24 h then AF were treated to the rats. In pineal gland samples, there were significant increases ofAAF after rats were treated with both compounds at the same time. However, luteolin treated for 24 h then AF were treated to the rats which increase AAF but decrease AF.

The mechanisms of apoptosis induced by diallyl disulfide (DADS) were explored in human cervical cancer Ca Ski cells. Flow cytometric analysis, DNA gel electrophoresis and DAPI staining demonstrated that DADS induced apoptosis in Ca Ski cells. DADS induced apoptosis through the production of reactive oxygen species and Ca2+, and induced abrogation of mitochondrial membrane potential (Deltapsim) and cleavage of Bid protein (t-Bid). DADS increased the levels of p53, p21 and Bax, but caused a decrease in the level of Bcl-2. DADS also promoted the activities of caspase-3 leading to DNA fragmentation, thus indicating that DADS-induced apoptosis is caspase-3 dependent. In addition, DADS induced an increase in the level of cytochrome c in the cytoplasm, which was released from mitochondria. BAPTA attenuated the Deltapsim abrogation and significantly diminished the occurrence of DADS-induced apoptosis in Ca Ski cells. In conclusion, DADS-induced apoptosis occurs via production of ROS and caspase-3 and a mitochondria-dependent pathway in Ca Ski cells.

The goal of this study was to analyze the potential risk factors determining surgical failure after sacrospinous suspension for uterine or vaginal vault prolapse. Each woman underwent a detailed history taking and a vaginal examination before treatment. Follow-up evaluations were at immediate post-operation, 1 week, 1 to 3 months, 6 months, 9 months, and annually after the operation. The surgical failure rate (27/168) following sacrospinous suspension was 16.1%. Using multivariable logistic regression, women with the presence of C or D point stage I at immediate post-operation were a significant risk factor for surgical failure after sacrospinous suspension (odds ratio, 35.34; 95% confidence interval, 8.75-162.75; p < 0.001). The success rate during the 18-month follow-up decreased significantly in women with the presence of C or D point stage I at immediate post-operation than stage 0. Although the sample size of women with symptomatic uterine or vaginal vault prolapse is small, impaired correction of anatomic defects is a significant risk factor for surgical failure of sacrospinous suspension.

Although it has been previously reported that bee venom (BV) can induce apoptosis in many cancer cell lines, there is no information on the effect of BV on human cervical cancer cells and its molecular mechanisms of action are not fully elucidated. In this study, the possible mechanisms of apoptosis by which BV acts on human cervical cancer Ca Ski cells were investigated. BV induced morphological changes and decreased the percentage of viable Ca Ski cells in a dose- and time-dependent manner. Flow cytometric analysis demonstrated that BV induced the production of reactive oxygen species, increased the level of cytoplasmic Ca2+, reduced mitochondrial membrane potential which led to cytochrome c release, and promoted the activation of caspase-3 which then led to apoptosis. BV also induced an increase in the levels of Fas, p53, p21 and Bax, but a decrease in the level of Bcl-2. The activities of both caspase-8 and caspase-9 were enhanced by BV, promoting caspase-3 activation, leading to DNA fragmentation. Based on the DNA fragmentation and DAPI staining, BV-induced apoptosis was mitochondrial-dependent and caspase-dependent. BV also promoted the expression of AIF and Endo G in the Ca Ski cells. Both AIF and Endo G proteins were released from the mitochondria, and then induced apoptosis which was not through activation of caspase. In conclusion, our data demonstrated that BV-induced apoptosis occurs via a Fas receptor pathway involving mitochondrial-dependent pathways and is closely related to the level of cytoplasmic Ca2+ in Ca Ski cells.

Gynostemma pentaphyllum Makino is known in Asia for its effect on the treatment of hepatitis and cardiovascular diseases. Gypenosides (Gyp) are the major components extracted from Gynostemma pentaphyllum Makino. However, the molecular mechanism underlying the Gyp-induced cell cycle arrest and apoptotic process is unclear. In this study, the chemopreventive role of Gyp in human lung cancer (A549) cells in vitro was evaluated by studying the regulation of the cell cycle and apoptosis. Gyp induced GO/G1 arrest and apoptosis in the human lung cancer A549 cells. Investigation of the cyclin-dependent protein kinase inhibitors by Western blotting showed that p16, p21, p27 and p53 proteins were increased with the increasing time of incubation with Gyp in the A549 cells. This increase may be the major factor by which Gyp caused GO/G1 arrest in the examined cells. Flow cytometric assay and gel electrophoresis of DNA fragmentation also confirmed that Gyp induced apoptosis in the A549 cells. Our data demonstrated that Gyp-induced apoptotic cell death was accompanied by up-regulation of Bax, caspase-3 and caspase-9, but down-regulation of the Bcl-2 levels. Taken together, Gyp appears to exert its anticancer properties by inducing GO/GI-phase arrest and apoptosis via activation of caspase-3 in human lung A549 cancer cells.

This study investigated whether mothers with prenatal environmental tobacco smoke (ETS) exposure increased the newborn genetic damage and adverse birth outcomes. Study participants were women receiving prenatal care at three hospitals in Central Taiwan and their newborns. Participants were divided into two groups (nonsmokers and ETS-exposed non-smokers) based on maternal ETS-exposed status. Comet assay were performed for cord blood samples. Infants born to mothers with prenatal ETS exposure had the highest mean cord blood DNA damage score (69.7 +/- 42.3) and poorer birth outcomes. No negative fetal growth effects appeared among newborns with low DNA damage levels. Among newborns with high DNA damage levels (comet scores >50), those born to prenatal ETS exposure had an average reduction of 252.7 g in birth weight, 1.10 cm shorter in length and a 0.92-cm decrease in head circumference, compared to newborns with no smoking exposure. This study shows that the DNA damage scores can be used as an effect-modifier on the relationships between ETS exposure and adverse birth outcome. The association appears more apparent for the ETS exposure in relation with more severe DNA damage.

Berberine, an isoquinoline alkaloid, has been shown to possess anticancer properties in some cancer cell lines. Here, we report that in vitro treatment of cervical cancer Ca Ski cells with berberine decreased the percentage of viable Ca Ski cells in a dose-dependent and time-dependent manner. Berberine enhanced the apoptosis of Ca Ski cells with the induction of a higher ratio of p53 and Bax/Bcl-2 proteins, increased levels of reactive oxygen species (ROS) and Ca2+, disruption of the mitochondrial membrane potential, and promotion of caspase-3 activity. In CaSki cells pretreated with the pan-caspase inhibitor zVAD-fmk, the berberine-induced caspase-3 activity and apoptosis were significantly blocked as confirmed by flow cytometric analysis. Western blot also showed that berberine induced the expression of GADD153, a transcription factor involved in apoptosis. Thus berberine increased ROS levels leading to endoplasmic reticulum (ER) stress based on the increase of GADD153 and shown by Ca2+ release from the ER. When the Ca Ski cells were pretreated with catalase, GADD153 production was abrogated and apoptosis was significantly reduced.

N-acetylation plays an important role in the metabolism of arylamine drugs and carcinogens and is catalyzed by cytosolic N-acetyltransferase (NAT). Gypenosides are the major components of Gynostemma pentaphyllum Makino which had been used as a natural folk medicine in the Chinese populations. Gypenosides were selected for examining the inhibition on the N-acetylation of 2-aminofluorene (AF), DNA-AF adduct formation and NAT gene expression in the human cervix epithelioid carcinoma cell line (HeLa). Various concentrations of gypenosides were individually added to the culture medium of human cervix epithelioid carcinoma cells (HeLa). The N-acetylation of AF was determined by high performance liquid chromatography (HPLC) assaying for the amounts of acetylated 2-aminofluorene (AAF) and nonacetylated 2-aminofluorene (AF). The N-acetylation of AF in the human HeLa cancer cells was suppressed by gypenosides in a dose-dependent manner. The data also demonstrated that gene expression (NAT1 mRNA) of NAT in human cervix epithelioid carcinoma cells (HeLa) was inhibited and decreased by gypenosides. After the incubation of HeLa cells with 30 or 60 microM AF and with or without 350 microg/ml gypenosides cotreatment, DNA was isolated and hydrolyzed to nucleotides, adducted nucleotides were extracted into butanol and analyzed DNA-AF adducts by HPLC. The data demonstrated that gypenosides decrease the levels of DNA-AF adduct formation in HeLa cells.