Programmed cell death (PCD) refers to the way in which cells die depending on specific genes encoding signals or activities. Apoptosis, autophagy, and pyroptosis are all mechanisms of PCD. Among these mechanisms, pyroptosis is mediated by the gasdermin family, accompanied by inflammatory and immune responses. The relationship between pyroptosis and cancer is complex, and the effects of pyroptosis on cancer vary in different tissues and genetic backgrounds. On one hand, pyroptosis can inhibit the occurrence and development of tumors; on the other hand, as a type of proinflammatory death, pyroptosis can form a suitable microenvironment for tumor cell growth and thus promote tumor growth. In addition, the induction of tumor pyroptosis is also considered a potential cancer treatment strategy. Studies have shown that DFNA5 (nonsyndromic hearing impairment protein 5)/GSDME (Gasdermin-E) mRNA methylation results in lower expression levels of DFNA5/GSDME in most tumor cells than in normal cells, making it difficult to activate the pyroptosis in most tumor cells. During the treatment of malignant tumors, appropriate chemotherapeutic drugs can be selected according to the expression levels of DFNA5/GSDME, which can be upregulated in tumor cells, thereby increasing the sensitivity to chemotherapeutic drugs and reducing drug resistance. Therefore, induced pyroptosis may play a predominant role in the treatment of cancer. Here, we review the latest research on the anti-and protumor effects of pyroptosis and its potential applications in cancer treatment. Facts Open questions 1. Does pyroptosis play differential roles in normal and tumor tissues? 2. What are the key signals that initiate pyroptosis? 3. What are the key signaling pathways impacted by pyroptosis in tumors? 4. How can pyroptosis be manipulated to drive tumor fate?
Pyroptosis, a type of programmed cell death mediated by gasdermin, is characterized by the swelling and rupture of cells, release of cellular contents and a strong inflammatory response, which is critical for controlling microbial infection. Pattern recognition receptors recognize the intracellular and extracellular pathogenic microbial components and stimulate the organism's inflammatory response by activating the pyroptosis signaling pathway and releasing interleukin‐1β (IL‐1β), IL‐18, and other inflammatory factors to promote pathogen clearance and prevent infection. In the process of continuous evolution, pathogens have developed multiple strategies to modulate the occurrence of pyroptosis and thus enhance their ability to induce disease; that is, the competition between host cells and pathogens controls the occurrence of pyroptosis. Competition can directly affect tissue inflammation outbreaks and even alter cell survival. Studies have shown that various bacterial infections, including Shigella flexneri, Salmonella, Listeria monocytogenes, and Legionella pneumophila, can lead to pyroptosis. Pyroptosis is associated with the occurrence and development of various diseases caused by microbial infection, and the identification of molecules related to the pyroptosis signaling pathway may provide new drug targets for the treatment of related diseases. This study reviews the molecular mechanisms of pyroptosis and the role of pyroptosis in microbial infection‐related diseases.
This article presents the generation of monoclonal antibodies (mAbs) with high specificity against 19-nortestosterone (NT) through cell fusion techniques and the development of a mAb-based indirect competitive ELISA (icELISA) method and colloidal gold-based immuno-chromatographic assay to detect NT residues in beef and pork samples. A modified carbodiimide method was employed to synthesize the artificial antigen, and BALB/c mice were used to produce anti-NT mAbs. On the basis of the checkerboard titration, an indirect competitive ELISA standard curve was established. This assay was sensitive and had a linear range from 0.03 to 38 ng/mL in phosphate buffered saline (PBS), with IC(50) and LOD values of 0.52 ng/mL and 0.01 ng/mL, respectively. Of all the competitive analogues, the produced mAb exhibited a high cross-reactivity to 17α-nortestosterone (83.6%), the main metabolite of NT in animal tissues. Except for moderate cross-reactivities with trenbolone (22.6%) and β-boldenone (13.8%), the other interference to the assay was negligible (<0.05%). In contrast, the strip test had a visual detection limit of 1 ng/mL in PBS, 2 μg/kg in beef, and 2 μg/kg in pork, respectively, and the results can be judged within 10 min. The ELISA and GC-MS results showed close correlation in beef (R2=0.9945) and in pork (R2=0.9977). Therefore, the combination of two immunoassays provides a useful screening method for quantitative or qualitative detection of NT residues in animal-origin products.
Modified 1-ethyl-3-(3-dimethylaminopropy) carbodiimide (EDC) method was employed to synthesize the artificial antigen of enrofloxacin (ENR), and New Zealand rabbits were used to produce anti-ENR polyclonal antibody (pAb). Based on the checkerboard titration, an indirect competitive enzyme-linked immunosorbent assay (ELISA) standard curve was established. This assay was sensitive and had a linear range from 0.6 to 148.0 μg/kg (R(2) = 0.9567), with the half maximal inhibitory concentration (IC(50)) and limit of detection (LOD) values of 9.4 μg/kg and 0.2 μg/kg, respectively. Of all the competitive analogues, the produced pAb exhibited a high cross-reactivity to ciprofloxacin (CIP) (87%), the main metabolite of ENR in tissues. After optimization, the matrix effects can be ignored using a 10-fold dilution in beef and 20-fold dilution in pork. The overall recoveries and coefficients of variation (CVs) were in the ranges of 86%-109% and 6.8%-13.1%, respectively. It can be concluded that the established ELISA method is suitable for simultaneous detection of ENR and CIP in animal tissues.
Modified 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) method was employed to synthesize the artificial antigen of norfloxacin (NOR), and New Zealand rabbits were used to produce anti-NOR polyclonal antibody (pAb). Based on the checkerboard titration, an indirect competitive enzyme-linked immunosorbent assay (icELISA) standard curve was established. This assay was sensitive and had a working range from 0.12 to 68.40 ng/ml, with the half maximal inhibitory concentration (IC 50 ) and limit of detection (LOD) values of 2.7 ng/ml and 0.06 ng/ml, respectively. The produced pAb exhibited high cross-reactivity to fluoroquinolones (FQs) tested, and the IC 50 values to enoxacin, ciprofloxacin, and pefloxacin were 3.1, 3.4, and 4.1 ng/ml, respectively. It also indicated that the concentrations of NaOH and methanol in assay buffer should not be higher than 10% and 30%. When spiked in milk at 5, 20, and 50 ng/ml, the recoveries for NOR, enoxacin, ciprofloxacin, and pefloxacin ranged 90.5%-98.0%, 84.0%-95.2%, 94.0%-106.0%, and 89.5%-100.0%, respectively. The results suggest that this class-specific pAb-based icELISA could be utilized for the primary screening of FQ residues in animal-original products.
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