Compared to traditional physical and chemical approaches, nanobiotechnology and plant-based green synthesis procedures offer significant advantages, as well as having a greater range of medical and biotechnological applications. Nanoparticles of zinc oxide (ZnO NPs) have recently been recognized as a promising option for many industries, including optics, electrics, packaged foods, and medicine, due to their biocompatibility, low cytotoxicity, and cost-effectiveness. Several studies have shown that zinc ions are important in triggering cell apoptosis by promoting the generation of reactive oxygen species (ROSs) and releasing zinc ions (Zn2+), which are toxic to cells. The toxic nature of the chemicals used in the synthesis of ZnO nanoparticles limits their clinical utility. An overview of recent developments in green ZnO NP synthesis is presented in this review, emphasizing plant parts as reducing agents and their medical applications, including their antimicrobial, anticancer, antioxidant, and anti-inflammatory properties, as well as key mechanisms of action for these applications to facilitate further research on the biomedical fields in the future.
BackgroundTumor glycolysis is a target for cancer chemotherapy. Methylglyoxal (MG) is a reactive metabolite formed mainly as a by-product in anaerobic glycolysis, metabolized by glyoxalase 1 (Glo1) of the glyoxalase system. We investigated the role of MG and Glo1 in cancer chemotherapy related in multidrug resistance (MDR).MethodsHuman Glo1 was overexpressed in HEK293 cells and the effect on anticancer drug potency, drug-induced increase in MG and mechanism of cytotoxicity characterized. Drug-induced increased MG and the mechanisms driving it were investigated and the proteomic response to MG-induced cytotoxicity explored by high mass resolution proteomics of cytoplasmic and other subcellular protein extracts. Glo1 expression data of 1,040 human tumor cell lines and 7,489 tumors were examined for functional correlates and impact of cancer patient survival.ResultsOverexpression of Glo1 decreased cytotoxicity of antitumor drugs, impairing antiproliferative activity of alkylating agents, topoisomerase inhibitors, antitubulins, and antimetabolites. Antitumor drugs increased MG to cytotoxic levels which contributed to the cytotoxic, antiproliferative mechanism of action, consistent with Glo1-mediated MDR. This was linked to off-target effects of drugs on glycolysis and was potentiated in hypoxia. MG activated the intrinsic pathway of apoptosis, with decrease of mitochondrial and spliceosomal proteins. Spliceosomal proteins were targets of MG modification. Spliceosomal gene expression correlated positively with Glo1 in human tumor cell lines and tumors. In clinical chemotherapy of breast cancer, increased expression of Glo1 was associated with decreased patient survival, with hazard ratio (HR) = 1.82 (logrank p < 0.001, n = 683) where upper quartile survival of patients was decreased by 64% with high Glo1 expression.ConclusionsWe conclude that MG-mediated cytotoxicity contributes to the cancer chemotherapeutic response and targets the spliceosome. High expression of Glo1 contributes to multidrug resistance by shielding the spliceosome from MG modification and decreasing survival in the chemotherapy of breast cancer. Adjunct chemotherapy with Glo1 inhibitor may improve treatment outcomes.
Semen is known to contain an ovulation-inducing factor (identified as a nerve growth factor, NGF) that shows a significant increase in ovulation after semen deposition in induced ovulatory species. However, the interplay between the male reproductive tract cells and oocyte maturation through messenger RNA (mRNA) cargo is yet to be investigated. Extracellular vesicles (EVs) from the primary culture of rabbit prostate (pEVs), epididymis (eEVs), and testis (tEVs) were isolated to examine their contents for several mRNA transcripts through relative quantitative PCR (RT-qPCR). The expressions of NGF, neurotrophin (NTF3), vascular endothelial growth factor A (VEGFA), A disintegrin and metalloprotease 17 (ADAM17), midkine (MDK), kisspeptin (KISS1), and gonadotrophin-releasing hormone (GNRH1) were examined in isolated EVs. EVs were characterized through transmission electron microscopy. EV uptake by cumulus cell culture was confirmed through microscopic detection of PKH26-stained EVs. Furthermore, the effects of pEVs, eEVs, and tEVs were compared with NGF (10, 20, and 30 ng/ml) supplementation on oocyte in vitro maturation (IVM) and transcript expression. KISS1, NTF3, MDK, ADAM17, GAPDH, and ACTB were detected in all EV types. GNRH1 was detected in tEVs. NGF was detected in pEVs, whereas VEGFA was detected in eEVs. pEVs, eEVs, and 20 ng/ml NGF showed the highest grade of cumulus expansion, followed by tEVs and 10 ng/ml NGF. Control groups and 30 ng/ml NGF showed the least grade of cumulus expansion. Similarly, first polar body (PB) extrusion was significantly increased in oocytes matured with eEVs, pEVs, tEVs, NGF20 (20 ng/ml NGF), NGF10 (10 ng/ml NGF), control, and NGF30 (30 ng/ml NGF). Additionally, the expression of NGFR showed a 1.5-fold increase in cumulus cells supplemented with eEVs compared with the control group, while the expression of PTGS2 (COX2) and NTRK showed 3-fold and 5-fold increase in NGF20-supplemented cumulus-oocyte complexes (COCs), respectively. Oocyte PMP15 expression showed a 1.8-fold increase in IVM medium supplemented with eEVs. Additionally, oocyte NGFR and NTRK expressions were drastically increased in IVM medium supplemented with pEVS (3.2- and 1.6-fold, respectively) and tEVs (4- and 1.7-fold, respectively). This is the first report to examine the presence of mRNA cargo in the EVs of male rabbit reproductive tract cells that provides a model for the stimulation of female rabbits after semen deposition.
Antibacterial resistance is observed as a public health issue around the world. Every day, new resistance mechanisms appear and spread over the world. For that reason, it is imperative to improve the treatment schemes that have been developed to treat infections caused by wound infections, for instance, Staphylococcus epidermidis (S. epidermidis), Proteus mirabilis (P. mirabilis), and Acinetobacter baumannii (A. baumannii). In this case, we proposed a method that involves mixing the Gentamicin (Gen) with iron oxide nanoparticles (Fe3O4 NPs) and a polymer (polyethylene glycol (PEG)) with Fe3O4 NPs. X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), energy dispersive X-ray (EDX), scanning electron microscope (SEM), and transmission electron microscope (TEM) were used to characterize Fe3O4 NPs. Zeta potential and dynamic light scattering (DLS) were also assessed. The antibacterial activity of Fe3O4 NPs, Fe3O4 NPs+PEG, Fe3O4 NPs+Gen, and Fe3O4 NPs+PEG+Gen composites was investigated. The results showed a significant improvement in the antibacterial activity of nanoparticles against bacterial isolates, especially for the Fe3O4 NPs+PEG+Gen as the diameter of the inhibition zone reached 26.33 ± 0.57 mm for A. baumannii, 25.66 ± 0.57 mm for P. mirabilis, and 23.66 ± 0.57 mm for S. epidermidis. The Fe3O4 NPs, Fe3O4 NPs+PEG, Fe3O4+Gen, and Fe3O4+PEG+Gen also showed effectiveness against the biofilm produced by these isolated bacteria. The minimum inhibitory concentration (MIC) of Fe3O4 NPs for S. epidermidis was 25 µg mL−1 and for P. mirabilis and A. baumannii was 50 µg mL−1. The findings suggest that the prepared nanoparticles could be potential therapeutic options for treating wound infections caused by S. epidermidis, P. mirabilis, and A. baumannii.
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