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Purpose. It is well documented that angiotensin II (Ang II) elevation promotes apoptosis of podocytes in vivo and vitro, but the potential mechanism is still oscular. The current study is aimed at probing into the assignment of cysteine-rich protein 61 (Cyr61) in Ang II-induced podocyte apoptosis. Methods. Podocytes were treated with Ang II (10-6 mol/L) for 48 hours to establish an injury model in vitro. Western blot assays were detected the expression of Cyr61, Cyt-c, Bax, and Bcl-2. Gene microarray was used to analyze the expression of mRNAs after treatment with Ang II. CRISPR/Cas9 technology was used to knock down Cyr61 and overexpress TXNIP gene, respectively. Results. The expression of Cyr61, TXNIP, Cyt-c, and Bax in podocytes treated with Ang II were upregulated, but the expression and apoptotic rates of Bcl-2 in podocytes were inhibited. The level of the above factors was not significantly different after the knockdown of Cyr61 with Ang II in podocytes. In Ang II group, when knocked down Cyr61, the expressed level of TXNIP, Cyt-c, and Bax was diminished after Ang II treatment; interestingly Bcl-2 expression and podocyte apoptotic rate were reduced. Under the stimulation of Ang II, the expression of Cyt-c and Bax were growing, whereas Bcl-2 was reduced, and the apoptotic rates were higher in the TXNIP overexpression group. Cyt-c and Bax were put on, whereas that of Bcl-2 was to be cut down when the Cyr61 was knockdown, and the apoptotic rates were gained in the TXNIP overexpression+Cyr61 knockdown group. Conclusions. The results of the study extrapolate that Cyr61 plays a dominant role in Ang II-induced podocyte apoptosis. Additionally, Cyr61 may mediate the Ang II-induced podocyte apoptosis by promoting the expression of TNXIP.

Coccinella septempunctata (ladybird) is an extremely important natural predator that feeds on aphids. An assessment of the toxicity of pesticides on environmental organisms is an essential component of Integrated Pest Management (IPM) strategies. This study evaluated diamide insecticides’ toxicity at lethal and 30% lethal doses (LR30) against C. septempunctata larvae. The pre-imaginal median lethal doses (LR50) of chlorantraniliprole 10% SC, tetrachlorantraniliprole 10% SC, and broflanilide 10% SC were calculated to be 42.078, 289.516, and 0.0943 g active ingredient (a.i.)/ha, respectively. The mortality tests demonstrated that chlorantraniliprole and tetrachlorantraniliprole are comparatively less toxic to C. septempunctata than broflanilide, which were detected to be highly toxic to C. septempunctata. The mortality rates of the groups treated with the three diamide insecticides tended to stabilize after 96 h, extending to the pre-imaginal stage. Furthermore, when compared to broflanilide, which had a much higher potential risk, the hazard quotient (HQ) values indicated that chlorantraniliprole and tetrachlorantraniliprole have a lower risk potential for C. septempunctata in farmland and off farmland. The LR30 dose induces abnormalities in the development phase 4th-instar larvae weight, pupal weight, and adult weight of treated C. septempunctata. The study emphasizes the importance of assessing the adverse effects of diamide insecticides on natural predator species that serve as biological control agents in agricultural IPM strategies.

Steroid alkaloids have been suggested as potential anticancer compounds. However, the underlying mechanisms of how steroid alkaloids inhibit the tumor growth are largely unknown. Here, we reported that solanine, a substance of steroid alkaloids, has a positive effect on the inhibition of pancreatic cancer cell growth in vitro and in vivo. In pancreatic cancer cells and nu/nu nude mice model, we found that solanine inhibited cancer cells growth through caspase-3 dependent mitochondrial apoptosis. Mechanically, solanine promotes the opening of mitochondrial membrane permeability transition pore (MPTP) by downregulating the Bcl- 2/Bax ratio; thereafter, Cytochrome c and Smac are released from mitochondria into cytosol to process the caspase-3 zymogen into an activated form. Moreover, we found that the expression of tumor metastasis related proteins, MMP-2 and MMP-9, was also decreased in the cells treated with solanine. Therefore, our results suggested that solanine was an effective compound for the treatment of pancreatic cancer. [ABSTRACT FROM AUTHOR]