We evaluated the activity of core-shell ZnO nanoparticles (ZnO-NPs@polymer shell) containing Oxaliplatin via polymerization through in vitro studies and in vivo mouse models of colorectal cancer. ZnO NPs were synthesized in situ when the polymerization step was completed by co-precipitation. Gadolinium coordinated-ZnONPs@polymer shell (ZnO-Gd NPs@polymer shell) was synthesized by exploiting Gd's oxophilicity (III). The biophysical properties of the NPs were studied using powder X-ray diffraction (PXRD), Fourier transforms infrared spectroscopy, Ultraviolet-visible spectroscopy (UV-Vis), field emission electron microscopy (FESEM), transmission electron microscopy (TEM), atomic force microscopy, dynamic light scattering, and z-potential. (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) was used to determine the antiproliferative activity of ZnO-Gd-OXA. Moreover, a xenograft mouse model of colon cancer was exerted to survey its antitumor activity and effect on tumor growth. In the following, the model was also evaluated by histological staining (H-E; Hematoxylin & Eosin and trichrome staining) and gene expression analyses through the application of RT-PCR/ELISA, which included biochemical evaluation (MDA, thiols, SOD, CAT). The formation of ZnO NPs, which contained a crystallite size of 16.8 nm, was confirmed by the outcomes of the PXRD analysis. The Plate-like morphology and presence of Pt were obtained in EDX outcomes. TEM analysis displayed the attained ZnO NPs in a spherical shape and a diameter of 33 ± 8.5 nm, while the hydrodynamic sizes indicated that the particles were highly aggregated. The biological results demonstrated that ZnO-Gd-OXA inhibited tumor growth by inducing reactive oxygen species and inhibiting fibrosis, warranting further research on this novel colorectal cancer treatment agent.
MicroRNAs (miRNAs) as post-transcriptionally regulators of gene expression have been shown to be critical regulators to fine-tuning immune responses, besides their criteria for being an ideal biomarker. The regulatory role of miRNAs in responses to most mastitis-causing pathogens is not well understood. Gram-positive Streptococcus uberis (Str. uberis), the leading pathogen in dairy herds, cause both clinical and subclinical infections. In this study, a system biology approach was used to better understand the main post-transcriptional regulatory functions and elements of bovine mammary gland response to Str. uberis infection. Publicly available miRNA-Seq data containing 50 milk samples of the ten dairy cows (five controls and five infected) were retrieved for this current research. Functional enrichment analysis of predicted targets revealed that highly confident responsive miRNAs (4 up- and 19 downregulated) mainly regulate genes involved in the regulation of transcription, apoptotic process, regulation of cell adhesion, and pro-inflammatory signaling pathways. Time series analysis showed that six gene clusters significantly differed in comparisons between Str. uberis-induced samples with controls. Additionally, other bioinformatic analysis, including upstream network analysis, showed essential genes, including TP53 and TGFB1 and some small molecules, including glucose, curcumin, and LPS, commonly regulate most of the downregulated miRNAs. Upregulated miRNAs are commonly controlled by the most important genes, including IL1B, NEAT1, DICER1 enzyme and small molecules including estradiol, tamoxifen, estrogen, LPS, and epigallocatechin. Our study used results of next-generation sequencing to reveal key miRNAs as the main regulator of gene expression responses to a Gram-positive bacterial infection. Furthermore, by gene regulatory network (GRN) analysis, we can introduce the common upregulator transcription factor of these miRNAs. Such milk-based miRNA signature(s) would facilitate risk stratification for large-scale prevention programs and provide an opportunity for early diagnosis and therapeutic intervention.