BackgroundUpregulation of Cyclin dependent kinase 1 (CDK1) protein is closely related with the prognosis of several malignant tumors. Chk1-CDC25C-CDK1 signaling and P53-P21WAF1-CDK1 signaling pathways are closely related with the cell cycle G2/M phase regulation. The present study aimed to analyze the relationship between CDK1 and the proliferation and apoptosis of ovarian cancer cells, investigate its molecular mechanism preliminarily.MethodsThe specific short-hair RNA (shRNA) plasmids and negative control plasmid of CDK1, checkpoint kinase 1 (CHK1) and p53 genes were transfected into ovarian cancer SK-OV-3 and OVCAR-3 cells respectively. The expressions of CDK1, CHK1 and p53 mRNA and CDK1, Chk1 and P53 protein were detected by sqRT-PCR and Western blot, levels of phospho-CDK1(Thr14/Tyr15), CyclinB1, phospho-Chk1(ser345), cell division cycle 25C (CDC25C), phospho-CDC25C(ser216), P21WAF1, phospho-P53(ser15), proliferating cell nuclear antigen (PCNA), Ki-67, Bcl-2, Bax, Caspase8, Cleaved-caspase3 and Cytochrome C were examined by Western blot. The cell proliferation was measured by MTT and Trypan blue exclusion assay respectively, the cell cycle phase distribution and cell apoptosis rate were detected by flow cytometry (FCM) assay.ResultsAs results of CDK1 inhibition by shRNA, the cell proliferation was repressed, the cell numbers of G2/M phase and cell apoptosis rate were increased in both SK-OV-3 and OVCAR-3 cells. After knockdown of CDK1, expressions of PCNA, Ki-67 and Bcl-2 protein were downregulated, expressions of Bax, Caspase8, Cleaved-caspase3 and Cytochrome C were upregulated. While knockdown the CHK1 and p53 by shRNA respectively, the similar effects were observed on the cell proliferation, cell cycle phase distribution and apoptosis in both SK-OV-3 and OVCAR-3 cells, as well as the expressions of the proliferation and apoptosis related proteins mentioned above. Moreover, the levels of p-CDK1(Thr14/Tyr15) were increased after either CHK1 inhibition or p53 inhibition.ConclusionsAbnormal activation of CDK1 was implicated in the proliferation and apoptosis regulation of ovarian cancer cells, which might be due to the aberrant regulations of the upstream Chk1-CDC25C and P53-P21WAF1 signaling pathway.
At present, foodborne diseases (FBDs) caused by bacteria are gradually increasing every year, and the development of new antibiotics is an urgent necessity for human beings. To find novel antibacterial compounds, three sponge-derived fungal strains (SCSIOS02F40, F46, and F49) were investigated. As a result, Alternaria sp. SCSIOS02F49 was selected for investigation on its secondary metabolites because its ethyl acetate (EtOAc) extract of potato dextrose broth (PDB) culture showed rich metabolites and strong antibacterial activity. Two new dibenzopyrones with rare sulfate group (1–2), together with 10 known compounds (3–12), were isolated from the Alternaria sp. SCSIOS02F49. Their structures were confirmed by nuclear magnetic resonance (NMR), mass spectrometry (MS) data, and comparison with data from the relevant literature. Almost all compounds showed moderate inhibitory activity against eight foodborne bacteria (FBB) with minimum inhibitory concentration (MIC) values in the range of 15.6–250 μg/ml, and minimum bactericidal concentration (MBC) values in the range of 31.3–250 μg/ml. The antibacterial mechanism of compound 1 was preliminarily investigated using growth curves, scanning electron microscopy (SEM), and flow cytometry (FCM), which revealed that compound 1 altered the external structure of Staphylococcus aureus and caused the rupture or deformation of the cell membranes. This research provides lead compounds for the development of new antibiotics or microbial preservatives.
Placenta percreta with bladder bleeding can occur during gestation or postpartum, posing a great threat to both mother and fetus. But it is rare and lacks standard management strategies. We reported four cases suffering from bladder bleeding caused by placenta percreta even with hemorrhagic shock admitted between January 1 st , 2011 and December 31 th , 2020 in The First Affiliated Hospital of Zhengzhou University. Clinical information, including age, gravidity and parity, ultrasound and magnetic resonance imaging manifestations, onset gestational age, bladder bleeding volume, clinical manifestations under bleeding, diagnosis, hemostatic methods, hospital stay, treatment cost, and prognosis, are presented. Two cases had bladder bleeding during the second trimester, respectively on the 22 +3 and 23 +5 weeks. Pregnancy was terminated timely. The other two cases had bladder bleeding on the 2 nd day post near-term cesarean section when activity. All the four cases achieved successful hemostasis following angiography and concomitant embolization for iliac vessels, and one of them received electrocoagulation hemostasis under cystoscopy, but failed. They all had favorable clinical outcomes and had no long-term complications. The neonatal outcome in the two cases that bladder hemorrhage occurred after near-term c-section was good. The newborns did not survive in two cases in which bladder hemorrhage occurred at the second trimester of pregnancy. Timely termination of pregnancy is recommended when such a condition develops during gestation. Diagnosis of bladder bleeding is relatively easy, for it is characterized by fast speed and large volume, with concomitant distension of the lower abdomen, blood discharge from the urethral orifice, or the indwelling catheter. Interventional embolization is an effective means to treat bladder bleeding caused by placenta percreta, while electrocoagulation hemostasis under cystoscopy must be applied with great caution. For the pregnant women with a high risk of placenta percreta, timely and accurate diagnosis should be achieved during the gestational age, and bladder bleeding should be concerned when placenta penetrates through the anterior wall of uterus.
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