SIRT5-mediated PRKAA2 succinylation ameliorates apoptosis of human placental trophoblasts in hypertensive disorder complicating pregnancy.

PURPOSE: Hypertensive disorder complicating pregnancy (HDCP) is a serious clinical disorder syndrome during pregnancy. This study aims at finding novel targets for HDCP therapy. METHODS: HDCP-related mRNAs were firstly screened out and subjected to gene enrichment analysis. We chose protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2) as the research object. Thirty-nine HDCP patients at 32 to 40 weeks of gestation were selected as the HDCP group, and 39 normal controls who received cesarean section delivery at 37-42 weeks of pregnancy were enrolled in this study. Chorionic villi samples were collected within 30 min of delivery. The apoptosis of isolated placental trophoblasts was monitored to investigate the regulatory role of PRKAA2. RESULTS: PRKAA2 expression was further proven to be enhanced in the placental tissues of HDCP patients compared with that of normal puerpera. Subsequently, the results of flow cytometry analysis and western blot indicated that PRKAA2 overexpression accelerated primary placental cell apoptosis, while its knockdown attenuated cell apoptosis. Mechanistically, we determined that the level of PRKAA2 succinylation was elevated in the placental tissue of HDCP patients. Through in vitro succinylation assay and mutagenesis, we confirmed that sirtuin 5 (SIRT5) interacts with PRKAA2 at K69 and K260 to induce PRKAA2 desuccinylation. SIRT5 regulated primary HDCP cell apoptosis through PRKAA2. Finally, the animal study revealed that PRKAA2 elevates the systolic blood pressure of HDCP rat model. CONCLUSION: Our findings indicated that SIRT5-mediated PRKAA2 succinylation modulates placental cell apoptosis in HDCP, suggesting that PRKAA2 is a potential therapeutic target for HDCP treatment.

Apigenin induces apoptosis and counteracts cisplatin-induced chemoresistance via Mcl-1 in ovarian cancer cells.

Ovarian cancer (OC) is one of the prominent causes of mortality in female patients diagnosed with gynecologic malignancies. While it has previously been demonstrated that apigenin inhibits cell growth in colon and breast cancer cells, the effect of apigenin in OC cells is not fully understood. Therefore, the aim of the present study was to investigate the impact of apigenin on cell death and resistance to cisplatin in OC cells. It was found that apigenin inhibited proliferation, hindered cell cycle progression and promoted SKOV3 cell apoptosis. Moreover, these effects were also observed in cisplatin-resistant SKOV3/DDP cells. Furthermore, apigenin reduced the mitochondrial transmembrane potential, and elevated the ratios of cleaved caspase-3/caspase-3 and Bax/Bcl-2 in the two cell types. Reverse transcription-quantitative PCR and western blotting results demonstrated that apigenin significantly downregulated Mcl-1 at the transcriptional and translational levels in SKOV3 and SKOV3/DDP cells, which was responsible for its cytotoxic functions and chemosensitizing effects. Collectively, the present results identified the impact of apigenin on OC cell death and resistance to cisplatin, and the potential molecular mechanisms. However, additional studies are required to further elucidate the underlying mechanisms.

Novel triazole analogs of apigenin-7-methyl ether exhibit potent antitumor activity against ovarian carcinoma cells via the induction of mitochondrial-mediated apoptosis.

Ovarian cancer is one of the main causes of cancer-associated mortality across the world. Currently, ovarian cancer is mainly treated with chemotherapy. However, ovarian cancer is detected at advanced stages and chemotherapy has numerous side effects. In addition, the results of current chemotherapy on the treatment of ovarian cancer are less than satisfactory. Therefore, there is an urgent need to develop novel and more viable chemotherapeutic agents that can be used to treat ovarian cancer. The present study was designed to synthesize a series of novel triazole analogs of the bioactive apigenin-7-methyl ether to evaluate its anticancer activity against three human ovarian cancer cell lines. A total of eight novel triazole derivatives were synthesized and screened for their anticancer activity. Of all the derivatives, a derivative named 3d exhibited significant and dose-dependent anticancer activity against the SKOV3 ovarian cancer cell line. The IC50 of 3d was found to be 10 µM against the SKOV3 cancer cell line. It was also observed that 3d induced apoptosis in SKOV3 cancer cells through the accretion of reactive oxygen species and reduction in mitochondrial membrane potential. The molecule also modulated the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein. Taken together, these results showed that the apigenein-7-methyl ether novel derivative 3d may prove an important lead molecule for the treatment of ovarian cancer.

[Spectral characteristics of different discharge modes in air dielectric barrier discharge].

The electron energy in the transition from streamer discharge to glow-like discharge in dielectric barrier discharge in air was investigated by using emission spectra. The vibrational temperature was measured with the N2 second positive band (C3II(u) --> B3II(g)) of the emission spectrum. The average electron energy was investigated from the relative intensity of the nitrogen molecular ion line at 391.4 nm and the nitrogen molecular line at 337.1 nm. It was found that the vibrational temperature and the relative intensity of nitrogen molecular ion line at 391.4 nm increased abruptly in the transition from streamer discharge to glow-like discharge. It was also found that the pressure for the transition pressure from streamer discharge to glow-like discharge changed with different gap distances, but the product of the transition pressure and gas gap width remained constant.

[Study on energy transfer in argon/air in dielectric barrier discharge by optical emission spectra].

The energy transfer in dielectric barrier discharge in argon/air mixture in a device with water electrodes was investigated by comparing the optical emission spectra in pure argon, argon/air mixture and air. It was observed that the intensities of argon spectral lines in argon/air discharge are all lower than that in argon discharge, which indicates that the nitrogen in air has a quenching effect on the argon excited states. It was found that the decreasing rate of intensity of spectral lines with increasing the air concentration is different. The intensity of ArI 763. 51 nm decreases fastest, the ArI 772.42 nm and ArI 696.54 nm take second place, while the ArI 750.39 nm decreases slowest. Comparing the excitation energy of argon excited state with the excitation energy of nitrogen molecule, the authors found that the smaller the difference between the excitation energy of argon excited state and the excitation energy of nitrogen molecule, the faster the spectral line decreases, implying the stronger the energy transfer. In addition, the additional argon in air makes the emission intensities of nitrogen band of second positive system and band of first negative system increase, which indicates that the excitation of nitrogen is enhanced by the energy transfer from argon through Penning excitation involving argon metastable states. In other words, the component and ratio of gas in the gas mixture influence the optical characteristic and energy transfer peculiarity in the mixed gas discharge. The optical emission spectra measurement as a useful plasma diagnostic tool has been successfully used in the study of energy transfer in the mixed gas discharge, and the results provide a reasonable reference for the underlying industrial applications of different species discharge.

[Influence of pressure on plasma temperature in air/argon dielecteic barrier discharge].

Electron excitation temperature and molecule vibrational temperature in argon/air dielectric barrier discharge (DBD) at different gas pressure with water electrodes were studied by using optical emission spectra. The spectral lines of Ar I 763. 51 nm(2P6 --> 1S5) and Ar I 772.42 nm(2P2 --> 1S3) were chosen to calculate electron excitation temperature by the relative intensity ratio method. The emission spectra of nitrogen band of second positive system ( C3 pi(u) --> B3 pi(g)) were measured at the same time. The molecule vibration temperature was estimated by the emission intensities of different bands with delta(nu) = -1, delta(nu) = -2, and delta(nU) = -3 in nitrogen band of second positive system, using Boltzmann's plot method. In addition, the relative line intensities of nitrogen (0-0) band of first negative system at 391.4 nm and (0-0) band of second positive system at 337.1 nm were also measured to study the variation of electron energy. It was found that the electron excitation temperature decreased from 4 700 to 3 300 K and the molecule vibrational temperature decreased from 3 200 to 2 900 K with increasing gas pressure from 20 to 60 kPa. Besides, the ratio of I(N2+)/I(N2) also decreased with pressure increasing from 20 to 60 kPa, indicating that the average electron energy decreases with the gas pressure increasing. These results are of great importance to the study of plasma dynamics of dielectric barrier discharge and also to the underlying industrial applications.

[Study on plasma temperature in dielectric barrier discharge at the middle value of pd].

The optical emission spectra of Ar/air dielectric barrier discharge (DBD) scanned from 300-800 nm near atmospheric pressure were obtained. Electron excitation temperature (T(exc)) and molecule vibrational temperature (T(v)) in Ar/air DBD at the middle value of pressure-distance (pd) product (about 6.4 x 10(3) Pa x cm) were studied. The ArI 763.51 nm(2P6 --> 1S5) and 772.42 nm(2P2 --> 1S3) lines were chosen to estimate T(exc). T(v) was measured by the N2 second positive band (C 3IIu --> B 3IIg). It was found that T(exc) and T(v) increase with increasing applied voltage. And the varying rate of T(exc) with increasing voltage is bigger than that of T(v).

Evolution-related amino acids play important role in determining regioselectivity of fatty acid desaturase from Pichia pastoris.

Omega(3)-fatty acid desaturase and Delta(12)-fatty acid desaturase of Pichia pastoris with distinguishable regioselectivity and high degree of sequence similarity were chosen for regioselectivity research. Chimeras were constructed in which Histidine-rich boxes 1, 2 and the carboxyl terminal region of omega(3)-fatty acid desaturase were replaced with corresponding region of Delta(12)-fatty acid desaturase. The replacement was found to result in a change of regioselectivity from omegay to x + 3 by functionally characterizing these chimeric enzymes in Saccharomyces cerevisae strain INVScI. Using site-directed mutagenesis, we further demonstrated that seven conserved amino acids of omega(3)-fatty acid desaturase within the first two Histidine-rich regions are responsible for the regioselectivity switch. Therefore, the regioselectivity of fatty acid desaturases may be better understood by investigating the evolutionary relationships of different fatty acid desaturases.