Integrin receptor-targeted, doxorubicin-loaded cerium oxide nanoparticles delivery to combat glioblastoma.

Aim: To assess the chemo-immunomodulatory effects of doxorubicin-loaded cerium oxide nanoparticles coated with oleyl amine-linked cyclic RGDfK peptide (CeNP+Dox+RGD) to target both gliomas and its tumor microenvironment (TME) via integrin receptors. Materials & methods: CeNP+Dox+RGD nanoparticles are synthesized by the sequential addition of cerium III chloride heptahydrate, beta-cyclodextrin, oleic acid, and F127 micelle (CeNP). Doxorubicin was then loaded into CeNPs and coated with oleyl amine-linked cyclic RGDfK peptide to form stable CeNP+Dox+RGD nanoparticles. Results: CeNP+Dox+RGD nanoparticles crossed blood-brain barrier (BBB) effectively and demonstrated threefold enhanced survivability in glioma-bearing mice. The IHC profiling of glial tumor cross-sections showed increased CD80 expression (M1 TAMs) and decreased arginase-1 expression (M2 TAMs). Conclusion: CeNP+Dox+RGD can be an immunotherapeutic treatment option to combat glioblastoma.

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Biosynthesized Silver Nanoparticles for Cancer Therapy and In Vivo Bioimaging.

In the current communication, a simple, environmentally compatible, non-toxic green chemistry process is used for the development of silver nanoparticles (AgZE) by the reaction between silver nitrate (AgNO3) and the ethanolic leaf extract of Zinnia elegans (ZE). The optimization of AgZE is carried out using a series of experiments. Various physico-chemical techniques are utilized to characterize the nanomaterials. The cell viability assay of AgZE in normal cells (CHO, HEK-293T, EA.hy926, and H9c2) shows their biocompatible nature, which is supported by hemolytic assay using mouse RBC. Interestingly, the nanoparticles exhibited cytotoxicity towards different cancer cell lines (U-87, MCF-7, HeLa, PANC-1 and B16F10). The detailed anticancer activity of AgZE on human glioblastoma cell line (U-87) is exhibited through various in vitro assays. In vivo the AgZE illustrates anticancer activity by inhibiting blood vessel formation through CAM assay. Furthermore, the AgZE nanoparticles when intraperitoneally injected in C57BL6/J mice (with and without tumor) exhibit fluorescence properties in the NIR region (excitation: 710 nm, emission: 820 nm) evidenced by bioimaging studies. The AgZE biodistribution through ICPOES analysis illustrates the presence of silver in different vital organs. Considering all the results, AgZE could be useful as a potential cancer therapeutic agent, as well as an NIR based non-invasive imaging tool in near future.

Dehydrozingerone ameliorates Lipopolysaccharide induced acute respiratory distress syndrome by inhibiting cytokine storm, oxidative stress via modulating the MAPK/NF-κB pathway.

BACKGROUND: Inflammation-mediated lung injury is a major cause of health problems in many countries and has been the leading cause of morbidity/mortality in intensive care units. In the current COVID-19 pandemic, the majority of the patients experienced serious pneumonia resulting from inflammation (Acute respiratory distress syndrome/ARDS). Pathogenic infections cause cytokine release syndrome (CRS) by hyperactivation of immune cells, which in turn release excessive cytokines causing ARDS. Currently, there are no standard therapies for viral, bacterial or pathogen-mediated CRS. PURPOSE: This study aimed to investigate and validate the protective effects of Dehydrozingerone (DHZ) against LPS induced lung cell injury by in-vitro and in-vivo models and to gain insights into the molecular mechanisms that mediate these therapeutic effects. METHODS: The therapeutic activity of DHZ was determined in in-vitro models by pre-treating the cells with DHZ and exposed to LPS to stimulate the inflammatory cascade of events. We analysed the effect of DHZ on LPS induced inflammatory cytokines, chemokines and cell damage markers expression/levels using various cell lines. We performed gene expression, ELISA, and western blot analysis to elucidate the effect of DHZ on inflammation and its modulation of MAPK and NF-κB pathways. Further, the prophylactic and therapeutic effect of DHZ was evaluated against the LPS induced ARDS model in rats. RESULTS: DHZ significantly (p < 0.01) attenuated the LPS induced ROS, inflammatory cytokine, chemokine gene expression and protein release in macrophages. Similarly, DHZ treatment protected the lung epithelial and endothelial cells by mitigating the LPS induced inflammatory events in a dose-dependent manner. In vivo analysis showed that DHZ treatment significantly (p < 0.001) mitigated the LPS induced ARDS pathophysiology of increase in the inflammatory cells in BALF, inflammatory cytokine and chemokines in lung tissues. LPS stimulated neutrophil-mediated events, apoptosis, alveolar wall thickening and alveolar inflammation were profoundly reduced by DHZ treatment in a rat model. CONCLUSION: This study demonstrates for the first time that DHZ has the potential to ameliorate LPS induced ARDS by inhibiting cytokine storm and oxidative through modulating the MAPK and NF-κB pathways. This data provides pre-clinical support to develop DHZ as a potential therapeutic agent against ARDS.

Differential expression dynamics of Growth differentiation factor9 (GDF9) and Bone morphogenetic factor15 (BMP15) mRNA transcripts during in vitro maturation of buffalo (Bubalus bubalis) cumulus-oocyte complexes.

The present study has evaluated the association of growth differentiation factor9 (GDF9) and bone morphogenetic protein15 (BMP15) mRNA expression in cumulus-oocyte complexes (COCs) of buffalo ovary during in vitro maturation (IVM). GDF9 and BMP15 are expressed specifically in mammalian oocytes and also participate in cumulus-oocyte crosstalk. Quantitative real-time polymerase chain reaction (qRT-PCR) technique was applied to investigate the relative abundance (RA) of GDF9 and BMP15 mRNA transcripts throughout the IVM process. Relative mRNA expression pattern of these specific genes were assessed in oocytes and cumulus cells at 0, 6, 12 and 24 h of in vitro culture. Our results revealed that RA of GDF9 during different hours of IVM showed significant reduction between 0 h and 24 h of maturation in oocytes and BMP15 transcript increased significantly (P<0.05) between 6 h and 12 h and decreased again between 12 h and 24. In cumulus cells, GDF9 remained stable during IVM upto 12 h of maturation and decreased significantly between 12 h and 24 h of maturation. Conversely, significant reduction of BMP15 was observed between 0 h and 6 h, stayed stable upto 12 h and became undetectable at 24 h of maturation. In conclusion, these two genes were differentially expressed during the period of oocyte maturation process and notably, BMP15 expression pattern is associated specifically with the period of cumulus cell expansion.