Novel Targets and Therapeutic Strategies to Protect Against Hepatic Ischemia Reperfusion Injury.

Hepatic ischemia reperfusion injury (IRI), a fascinating topic that has drawn a lot of interest in the last few years, is a major complication caused by a variety of clinical situations, such as liver transplantation, severe trauma, vascular surgery, and hemorrhagic shock. The IRI process involves a series of complex events, including mitochondrial deenergization, metabolic acidosis, adenosine-5'-triphosphate depletion, Kupffer cell activation, calcium overload, oxidative stress, and the upregulation of pro-inflammatory cytokine signal transduction. A number of protective strategies have been reported to ameliorate IRI, including pharmacological therapy, ischemic pre-conditioning, ischemic post-conditioning, and machine reperfusion. However, most of these strategies are only at the stage of animal model research at present, and the potential mechanisms and exact therapeutic targets have yet to be clarified. IRI remains a main cause of postoperative liver dysfunction, often leading to postoperative morbidity or even mortality. Very recently, it was reported that the activation of peroxisome proliferator-activated receptor γ (PPARγ), a member of a superfamily of nuclear transcription factors activated by agonists, can attenuate IRI in the liver, and FAM3A has been confirmed to mediate the protective effect of PPARγ in hepatic IRI. In addition, non-coding RNAs, like LncRNAs and miRNAs, have also been reported to play a pivotal role in the liver IRI process. In this review, we presented an overview of the latest advances of treatment strategies and proposed potential mechanisms behind liver IRI. We also highlighted the role of several important molecules (PPARγ, FAM3A, and non-coding RNAs) in protecting against hepatic IRI. Only after achieving a comprehensive understanding of potential mechanisms and targets behind IRI can we effectively ameliorate IRI in the liver and achieve better therapeutic effects.

Effects of prophylactic uterine artery embolization on second-trimester induced abortions in patients with placenta previa.

OBJECTIVE: To evaluate the effects of prophylactic uterine artery embolization (UAE) on second-trimester induced abortions in patients with placenta previa. METHODS: The present study was a retrospective review of second-trimester induced abortions in the presence of placenta previa that conducted between January 1, 2008, and October 31, 2017, at a university hospital in Hangzhou, China. Pregnancy outcomes including intraoperative blood loss, transfusion, dilatation and evacuation, hysterotomy delivery, and hysterectomy were compared between patients with and without prophylactic UAE. RESULTS: There were 54 patients included in the study. In patients with partial placenta previa (n=15), the volume of intraoperative blood loss and the frequency of dilatation and evacuation were not significantly different between the UAE and non-UAE groups (P>0.05). No patient had a transfusion, hysterotomy delivery, or hysterectomy. Among patients with complete placenta previa (n=39), the volumes of intraoperative blood loss (P=0.014) and transfusion (P=0.046) were significantly lower in the UAE group compared with the non-UAE group. The rates of dilatation and evacuation, and hysterotomy delivery did not differ between the groups (P>0.05), but were numerically higher in the non-UAE group. No patient was treated with hysterectomy. CONCLUSION: Prophylactic UAE before a second-trimester induced abortion had significant advantages in women with complete placenta previa, but it did not improve the pregnancy outcome in patients with partial placenta previa. CHINESE CLINICAL TRIAL REGISTRY: ChiCTR-OPC-14005334.

Aquaporin 5 Plays a Role in Estrogen-Induced Ectopic Implantation of Endometrial Stromal Cells in Endometriosis.

Aquaporin 5 (AQP5) participates in the migration of endometrial cells. Elucidation of the molecular mechanisms associated with AQP5-mediated, migration of endometrial cells may contribute to a better understanding of endometriosis. Our objectives included identifying the estrogen-response element (ERE) in the promoter region of the AQP5 gene, and, investigating the effects of AQP5 on ectopic implantation of endometrial cells. Luciferase reporter assays and electrophoretic mobility shift assay (EMSA) identified the ERE-like motif in the promoter region of the AQP5 gene. After blocking and up-regulating estradiol (E2) levels, we analysed the expression of AQP5 in endometrial stromal (ES) cells. After blocking E2 /or phosphatidylinositol 3 kinase(PI3K), we analysed the role of AQP5 in signaling pathways. We constructed an AQP5, shRNA, lentiviral vector to knock out the AQP5 gene in ES cells. After knock-out of the AQP5 gene, we studied the role of AQP5 in cell invasion, proliferation, and the formation of ectopic endometrial implants in female mice. We identified an estrogen-response element in the promoter region of the AQP5 gene. Estradiol (E2) increased AQP5 expression in a dose-dependent fashion, that was blocked by ICI182,780(an estrogen receptor inhibitor). E2 activated PI3K /protein kinase B(AKT) pathway (PI3K/AKT), that, in turn, increased AQP5 expression. LY294002(PI3K inhibitor) attenuated estrogen-enhanced, AQP5 expression. Knock-out of the AQP5 gene with AQP5 shRNA lentiviral vector significantly inhibited E2-enhanced invasion, proliferation of ES cells and formation of ectopic implants. Estrogen induces AQP5 expression by activating ERE in the promoter region of the AQP5gene, activates the PI3K/AKT pathway, and, promotes endometrial cell invasion and proliferation. These results provide new insights into some of the mechanisms that may underpin the development of deposits of ectopic endometrium.

[AQP5 gene silencing inhibits proliferation and migration of ectopic endometrial glandular epithelial cells in endometriosis].

OBJECTIVE: To investigate the effect of aquaporin 5(AQP5) on proliferation and migration of ectopic endometrial epithelial cells. METHODS: AQP5 shRNA interference fragments were designed and transfected into ectopic endometrial epithelial cells stably by lentivirus technology. Fluorescence quantitative RT-PCR and Western blotting were used to detect the AQP5 mRNA and protein expression, respectively. The cell proliferation and migration were determined by using MTT method and Transwell system, respectively. Levels of phosphorylated AKT(p-AKT) and total AKT were examined by Western blotting. The nude mice model of endometriosis was constructed and the endometrial cell nodule formation was observed. RESULTS: AQP5 shRNA transfection inhibited cell proliferation and migration compared with control group (both P<0.05). The activation of AKT in AQP5 shRNA transfected cells was lower than that in control cells (P<0.01). Compared to control group, the endometrial cells nodule formation was suppressed in mice inoculated with AQP5 shRNA-silencing ectopic endometrial epithelial cells. CONCLUSION: Down-regulation of AQP5 expression can suppress the proliferation and migration of ectopic endometrial epithelial cells and endometrial cell nodule formation in nude mice, in which AKT pathway may be involved.

Reduced migration of Ishikawa cells associated with downregulation of aquaporin-5.

Aquaporin (AQP)-dependent cell migration has broad implications in angiogenesis, tumor metastasis, wound healing, glial scarring and other events requiring cell movement. There are 13 isoforms of AQP (0-12) that have been identified in mammals. It is unclear whether AQP5 plays a role in the development of endometrial cancer. We recently demonstrated that ovarian steroids may affect the expression of AQP5 in the female genital tract. In this study, we considered whether AQP5 may affect cell migration in Ishikawa cells, an adenocarcinoma cell line derived from the endometrium. The results showed that the downregulation of AQP5 results in reduced Ishikawa cell migration. The estrogen (E2) receptor in the promoter of AQP5 mediated the regulation of AQP5 expression in the normal endometrium and endometrial cancer. By contrast, the upregulation of AQP5 by E2 increased cell migration, invasion and adhesion through increased annexin-2, which is responsible for F-actin remodeling and rearrangement. E2 regulates Ishikawa cell migration by regulating the AQP5 expression.

Polydatin attenuates hypoxic pulmonary hypertension and reverses remodeling through protein kinase C mechanisms.

Hypoxic pulmonary hypertension is a life-threatening emergency if untreated. Consistent pulmonary hypertension also leads to arteries and ventricular remodeling. The clinical therapeutic strategy for pulmonary hypertension and the corresponding remodeling mainly interacts with NO, angiotensin II (Ang II) and elevated endothelin (ET) targets. In the present study, we evaluated the effects of polydatin on hypoxia-induced pulmonary hypertension. It was observed that polydatin attenuated hypoxic pulmonary hypertension, reversed remodeling, and regulated NO, Ang II, ET contents in the serum and lung samples. However, forced activation of PKC signaling by its selective activator thymeleatoxin (THX) could abate the effects of polydatain. These results suggest that polydatin might be a promising candidate for hypoxic pulmonary treatment through interaction with PKC mechanisms.

Mutation of an X chromosome in aggressive angiomyxoma: Report of a case and review of the literature.

► Cytogenetic analysis performed on peripheral blood showed a similar abnormal chromosomal complement in tumor tissue. ► Thus, mutation of an X chromosome appears to be confined to the neoplasm. ► This anomaly has not been previously described in aggressive angiomyxoma.

Immunohistochemical detection of aquaporin expression in eutopic and ectopic endometria from women with endometriomas.

OBJECTIVE: To investigate the expression of aquaporin (AQP) in eutopic and ectopic endometrial tissues from women with endometriomas. DESIGN: Controlled laboratory research. SETTING: Hospital-based unit for gynecology and obstetrics and research laboratories. PATIENT(S): Premenopausal women undergoing laparoscopy for endometriomas. INTERVENTION(S): Endometrial biopsy samples obtained from 70 women with endometriomas. MAIN OUTCOME MEASURE(S): Semiquantitative analysis by immunohistochemistry. RESULT(S): Aquaporins 2, 5, and 8 were mainly located in luminal and glandular epithelia. The frequency of positive immunostaining for aquaporins 2, 5, and 8 decreased in ectopic compared with eutopic endometria. Aquaporins 2, 5, and 8 were found at a low frequency in the endometria in early proliferative phases but at a higher frequency in late proliferative and secretory phases. There were no significant differences in the menstrual cycle of the proliferative phase and secretory phase in the two groups. CONCLUSION(S): Aquaporins 2, 5, and 8 were expressed with greater frequency in eutopic endometrial cells than inectopic endometrial cells, suggesting that eutopic endometrial cells have stronger migration activity than ectopic endometrial cells in women with endometriosis.

[DNA and RNA random amplification polymorphism in 5-flurocytosine-resistant strains of Candida albicans from revul-vaginal candidasis].

OBJECTIVE: To investigate the DNA genome and RNA expression in 5-flurocytosine-resistant strains of Candida albicans from vaginal candidasis. METHODS: Sixteen strains of Candida albicans were selected from clinically diagnosed revul-vaginal candidasis. Eight 5-flurocytosine-sensitive isolates and 8 resistant isolates were examined by France Media FUNGUS sensitive test. DNA genome was detected with random amplification polymorph DNA. RNA expression was detected with random amplification polymorph RNA method. RESULTS: There were no distinct differences between 5-flurocytosine-sensitive and resistant Candida albicans in DNA genome, while RNA expression showed significant differences between 5-flurocytosine-resistant and sensitive strains. CONCLUSION: Clinical 5-flurocytosine-resistant strains of Candida albicans from revul-vaginal candidasis may be related to phenotype changes.