Ajmalicine induces the pyroptosis of hepatoma cells to exert the antitumor effect.

Ajmalicine (AJM) is an alkaloid extracted from the root of Yunan Rauvolfia verticillata. At present, little research has reported the antitumor pharmacological action and mechanism of AJM. Therefore, this work aimed to conduct relevant research. The mouse hepatoma cell line H22 was intervened with a gradient concentration of AJM. Subsequently, the pyroptosis level was detected by flow cytometry. The expression of inflammatory factors and lactate dehydrogenase was measured by enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) expression was detected by dichlorodihydrofluorescein diacetate probe. In addition, the tumor-bearing model mice were also treated with AJM to analyze tumor growth as well as the expression levels of tissue inflammatory factors and proteins. According to our results, AJM promoted the pyroptosis of H22 cells, increased the pyroptosis rate, and upregulated the expression of inflammatory factors tumor necrosis factor α, interleukin-1ß, and interleukin-6. At the same time, it enhanced the openness of membrane pores and increased the expression of ROS. Moreover, AJM promoted the expression of Caspase-3 and N-terminal gasdermin E (GSDME). The AJM-induced pyroptosis was suppressed after N-acetylcysteine treatment to inhibit ROS, while Caspase-3 knockdown also inhibited the AJM-induced pyroptosis. In animals, AJM suppressed tumor growth. AJM can activate ROS to induce pyroptosis and exert the antitumor effect via the noncanonical Caspase-3-GSDME pyroptosis pathway.

Myrrhone inhibits the progression of hepatic fibrosis by regulating the abnormal activation of hepatic stellate cells.

We focus on exploring the antihepatic fibrosis effect of Myrrhone (Myr), a compound extracted from myrrh, and its effective target. Mouse hepatic stellate cells (HSCs) were cultured in vitro and activated by transforming growth factor-ß induction. After Myr intervention, cell viability was assessed by the Cell Counting Kit-8 assay. The α-smooth muscle actin(α-SMA) and Collagen I levels were measured by immunofluorescence, and the expressions of tumor necrosis factor-α, interleukin-6, and matrix metalloproteinase-9 were examined by enzyme-linked immunosorbent assay, and the p-Smad3 protein level in HSCs was determined by Western Blot. Small molecule-protein docking and pull-down experiments were conducted to validate the binding capacity between Nard and Smad3. In animal experiments, a mouse model of hepatic fibrosis was established with carbon tetrachloride. Myr was administered by gavage daily to determine the serum alanine aminotransferase and aspartate transaminase levels. The severity of hepatic fibrosis was evaluated by Masson staining, the α-SMA and Collagen I expressions were measured by immunohistochemistry, and the histopathological changes were examined by Sirius red and hematoxylin and eosin staining. Myr suppressed the abnormal activation of HSCs, inhibited the cell viability, downregulated the α-SMA and Collagen I, and inhibited the p-Smad3 expression. After silencing Smad3, the effect of Myr was inhibited. Molecular docking and pull-down experiments revealed the presence of a targeted binding relationship between Myr and Smad3. In mouse experiments, Myr could inhibit hepatic fibrosis. This study discovers that Myr can affect the phosphorylation of Smad3, and inhibit the activation of HSCs and the progression of hepatic fibrosis.

Label-free real-time ultrasensitive monitoring of non-small cell lung cancer cell interaction with drugs.

The timely discovery of cancer cell resistance in clinical processing and the accurate calculation of drug dosage to reduce and inhibit tumour growth factor in cancer patients are promising technologies in cancer therapy. Here, an optofluidic resonator effectively detects drug interactions with cancer cell processing in real time and enables the calculation of label-free drug-non-small cell lung cancer (NSCLC) epidermal growth factor receptor (EGFR) and binding ratios using molecular fluorescence intensity. According to clinical test and in vivo experimental data, the efficiencies of gefitinib and erlotinib are only 37% and 12% compared to AZD9291, and 0.300 µg of EGFR inactivation requires 0.484 µg of AZD9291, 0.815 µg of gefitinib and 1.348 µg of erlotinib. Experimental results show that the present method allows for the performance detection of drug resistance and for the evaluation of dosage usage.