2+channel CaV1.2 subtype in ANSCs. Together, these findings suggest that AQP4 plays a crucial role in regulating the proliferation, migration and differentiation of ANSCs, and this function of AQP4 is probably mediated by its action on intracellular Ca 2+ dynamics.

Berberine has drawn extensive attention toward their wide range of biochemical and pharmacological effects, including antineoplastic effect in recent years, but the precise mechanisms remain unclear. Treatment of human breast cancer cells (MCF-7 and MDA-MB-231 cells) with berberine induced inhibition of cell viability in concentration- and time-dependent manner irrespective of their estrogen receptor (ER) expression. Hoechst33342 staining confirmed berberine induced breast cancer cell apoptosis in time-dependent manner. Because apoptosis induction is considered to be a crucial strategy for cancer prevention and therapy, berberine may be an effective chemotherapeutic agent against breast cancer. To explore the precise mechanism, berberine-induced oxidative stress and mitochondrial-related apoptotic pathway in human breast cancer cells were investigated in this study. In both MCF-7 and MDA-MB-231 cells, berberine increased the production of reactive oxygen species (ROS), which activated the pro-apoptotic JNK signaling. Phosphorylated JNK triggered mitochondria membrane potential (ΔΨm) depolarization and downregulation expression of anti-apoptotic protein Bcl-2 concomitant with the upregulation expression of pro-apoptotic protein Bax. Downregulation of anti-apoptotic Bcl-2 family protein in parallel with loss of ΔΨm, leading to increased the release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria, and eventually triggered the caspase-dependent and caspase-independent apoptosis. Taken together, our study reveled that berberine exerted an antitumor activity in breast cancer cells by reactive oxygen species generation and mitochondrial-related apoptotic pathway. These finding provide an insight into the potential of berberine for breast cancer therapy.

Opening of ATP-sensitive potassium (K(ATP)) channels has been demonstrated to exert significant neuroprotection in in vivo and in vitro models of Parkinson's disease (PD), but the exact mechanism remains unclear. In the present study, various K(ATP) channel openers (KCOs) sensitive to diverse K(ATP) subunits were used to clarify the protective role of K(ATP) channel opening in 1-methyl-4-phenylpyridinium (MPP(+))-induced oxidative stress injury in mouse primary cultured mesencephalic neurons. The results showed that pretreatment with nonselective KCO pinacidil (Pin) or diazoxide (Dia), a KCO sensitive to Kir6.2/SUR1 K(ATP) channels, protected mesencephalic neurons, especially dopaminergic neurons, against MPP(+)-induced injury in a concentration-dependent manner. However, cromakalim (Cro), an opener of Kir6.1/SUR2 but not Kir6.2/SUR1 K(ATP) channels, failed to protect against MPP(+)-induced cytotoxicity. Furthermore, Pin and Dia but not Cro significantly suppressed the elevation of reactive oxygen species (ROS) triggered by MPP(+) and prevented the loss of mitochondrial member potential (Delta Psi m) and the release of mitochondrial cytochrome c. Consequently, opening of K(ATP) channels expressed in neurons could protect primary mesencephalic neurons against MPP(+)-induced cytotoxicity via inhibiting ROS overproduction and subsequently ameliorating mitochondrial function.

Autophagy, identified as type II programmed cell death, has already been known to be involved in the pathophysiology of preeclampsia (PE), which is a gestational disease with high morbidity. The present study aims to investigate the functional role of let-7i, a miRNA, in trophoblastic autophagy. Placental tissue used in this study was collected from patients with severe preeclampsia (SPE) or normal pregnant women. A decreased level of let-7i was found in placenta of SPE. In addition, autophagic vacuoles were observed in SPE and the expression of microtubule associated protein 1 light chain 3 (LC3) II/I was elevated. In vitro, let-7i mimics suppressed the autophagic activities in human HTR-8/SVneo trophoblast cell line (HTR-8) and human placental choriocarcinoma cell line JEG-3, whereas let-7i inhibitor enhanced the activities. As a potential target of let-7i, autophagy-related 4B cysteine peptidase (Atg4B) had an increased expression level in SPE. As expected, the increased expression of Atg4B was negatively regulated by let-7i using dual luciferase reporter assay. Furthermore, these trophoblast-like cells transfected with the let-7i mimic or inhibitors resulted in a significant change of Atg4B in both mRNA and protein level. More importantly, Atg4B overexpression could partly reverse let-7i mimic-reduced LC3II/I levels; whereas Atg4B silencing partly attenuated let-7i inhibitor-induced the level of LC3II/I expression. Taken together, these findings suggest that let-7i is able to regulate autophagic activity via regulating Atg4B expression, which might contribute to the pathogenesis of PE. J. Cell. Physiol. 232: 2581-2589, 2017. © 2016 Wiley Periodicals, Inc.

The endometrium undergoes a pregnancy-delivery-repair cycle multiple times during the reproductive lifespan in females. Decidualization is one of the critical events for the success of this essential process. We have previously reported that Notch1 is essential for artificial decidualization in mice. However, in a natural pregnancy, the deletion of Notch1 (PgrCre/+Notch1f/f, or Notch1d/d) only affects female fertility in the first 30 days of a 6-month fertility test, but not the later stages. In the present study, we undertook a closer evaluation at the first pregnancy of these mice to attempt to understand this puzzling phenomenon. We observed a large number of pregnancy losses in Notch1d/d mice in their first pregnancy, which led to the subfertility observed in the first 30 days of the fertility test. We then demonstrated that the initial pregnancy loss is a consequence of impaired decidualization. Furthermore, we identified a group of genes that contribute to Notch1 regulated decidualization in a natural pregnancy. Gene ontogeny analysis showed that these differentially expressed genes in the natural pregnancy are involved in cell–cell and cell–matrix interactions, different from genes that have been previously identified from the artificial decidualization model, which contribute to cell proliferation and apoptosis. In summary, we determined that Notch1 is essential for normal decidualization in the mouse uterus only in the first pregnancy but not in subsequent ones.

Objectives: This study was carried out to systematically evaluate the efficacy and safety of pre-exchange transfusion (pre-ET) albumin infusion on neonatal hyperbilirubinemia. Methods: A comprehensive search of relevant studies from EMBASE, Medline, Cochrane Register of Controlled Trials, ClinicalTrials.gov, China National Knowledge Infrastructure, Wei Pu Information, Wan Fang Data, and Chinese Biomedical Literature Database was conducted from inception to December 2021. Two different authors screened the titles, abstracts, and full texts of the articles. The quality of the included trials was assessed independently by two different authors according to the Cochrane Collaboration’s Risk of Bias. The data were analyzed and compiled using Review Manager software (RevMan version 5.3). Results: In total, four studies enrolling 195 neonates were included in this review. The quality of the included studies was deemed fair to good. The meta-analysis showed that pre-ET albumin infusion was superior to exchange transfusion (ET) alone for reducing the need for repeating ET (risk ratio (RR) = 0.25, 95% confidence interval (CI): 0.09 - 0.72, I-squared (I2) = 8%; fixed effects model) and shortening the duration of phototherapy (PT) (mean difference (MD) = -11.46 hours, 95% CI: -16.56 to -6.36, I2 = 93%; random effects model (REM)). No significant differences were detected between the two groups for post-ET total serum bilirubin (TSB) at 6 hours (MD = -3.51 mg/dL, 95% CI: -7.93 - 0.93, I2 = 97%; REM) and 12 hours (MD = -4.21 mg/dL, 95% CI: -9.08 - 0.65, I2 = 99%; REM). None of the patients developed acute bilirubin encephalopathy in any of the trials. No death prior to hospital discharge was reported in any trials, and no adverse effects were observed in intervention groups. Conclusions: Based on four studied trials, pre-ET albumin infusion appears to be safe and effective in reducing the need for repeating ET and shortening PT duration. These potential benefits, including the reduction of post-ET TSB, need to be revalidated in future trials using rigorous methodology.

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