Curcumin coating: a novel solution to mitigate inherent carbon nanotube toxicity.

Multi-walled Carbon Nanotubes (MWCNTs) are inert structures with high aspect ratios that are widely used as vehicles for targeted drug delivery in cancer and many other diseases. They are largely non-toxic in nature however, when cells are exposed to these nanotubes for prolonged durations or at high concentrations, they show certain adverse effects. These include cytotoxicity, inflammation, generation of oxidative stress, and genotoxicity among others. To combat such adverse effects, various moieties can be attached to the surface of these nanotubes. Curcumin is a known anti-inflammatory, antioxidant and cytoprotective compound derived from a medicinal plant called Curcuma longa. In this study, we have synthesized and characterized Curcumin coated-lysine functionalized MWCNTs and further evaluated the cytoprotective, anti-inflammatory, antioxidant and antiapoptotic effect of Curcumin coating on the surface of MWCNTs. The results show a significant decrease in the level of inflammatory molecules like IL-6, IL-8, IL-1ß, TNFα and NFκB in cells exposed to Curcumin-coated MWCNTs as compared to the uncoated ones at both transcript and protein levels. Further, compared to the uncoated samples, there is a reduction in ROS production and upregulation of antioxidant enzyme-Catalase in the cells treated with Curcumin-coated MWCNTs. Curcumin coating also helped in recovery of mitochondrial membrane potential in the cells exposed to MWCNTs. Lastly, cells exposed to Curcumin-coated MWCNTs showed reduced cell death as compared to the ones exposed to uncoated MWCNTs. Our findings suggest that coating of Curcumin on the surface of MWCNTs reduces its ability to cause inflammation, oxidative stress, and cell death.

SARS-CoV-2 envelope protein induces necroptosis and mediates inflammatory response in lung and colon cells through receptor interacting protein kinase 1.

SARS-CoV-2 Envelope protein (E) is one of the crucial components in virus assembly and pathogenesis. The current study investigated its role in the SARS-CoV-2-mediated cell death and inflammation in lung and gastrointestinal epithelium and its effect on the gastrointestinal-lung axis. We observed that transfection of E protein increases the lysosomal pH and induces inflammation in the cell. The study utilizing Ethidium bromide/Acridine orange and Hoechst/Propidium iodide staining demonstrated necrotic cell death in E protein transfected cells. Our study revealed the role of the necroptotic marker RIPK1 in cell death. Additionally, inhibition of RIPK1 by its specific inhibitor Nec-1s exhibits recovery from cell death and inflammation manifested by reduced phosphorylation of NFκB. The E-transfected cells' conditioned media induced inflammation with differential expression of inflammatory markers compared to direct transfection in the gastrointestinal-lung axis. In conclusion, SARS-CoV-2 E mediates inflammation and necroptosis through RIPK1, and the E-expressing cells' secretion can modulate the gastrointestinal-lung axis. Based on the data of the present study, we believe that during severe COVID-19, necroptosis is an alternate mechanism of cell death besides ferroptosis, especially when the disease is not associated with drastic increase in serum ferritin.

Comprehensive insight into altered host cell-signaling cascades upon Helicobacter pylori and Epstein-Barr virus infections in cancer.

Cancer is characterized by mutagenic events that lead to disrupted cell signaling and cellular functions. It is one of the leading causes of death worldwide. Literature suggests that pathogens, mainly Helicobacter pylori and Epstein-Barr virus (EBV), have been associated with the etiology of human cancer. Notably, their co-infection may lead to gastric cancer. Pathogen-mediated DNA damage could be the first and crucial step in the carcinogenesis process that modulates numerous cellular signaling pathways. Altogether, it dysregulates the metabolic pathways linked with cell growth, apoptosis, and DNA repair. Modulation in these pathways leads to abnormal growth and proliferation. Several signaling pathways such RTK, RAS/MAPK, PI3K/Akt, NFκB, JAK/STAT, HIF1α, and Wnt/ß-catenin are known to be altered in cancer. Therefore, this review focuses on the oncogenic roles of H. pylori, EBV, and its associated signaling cascades in various cancers. Scrutinizing these signaling pathways is crucial and may provide new insights and targets for preventing and treating H. pylori and EBV-associated cancers.