Ginger's Antiapoptotic and Antioxidant Effects on Ovaries of Cyclophosphamide-therapied Rats.

BACKGROUND: In the recent decade, there has been increasing interest in preventing ovarian toxicity after chemotherapy exposure. It has been documented that ginger (Zingiber officinale) might normalize the hormonal balance and control the menstrual cycle.. OBJECTIVE: This study has analyzed whether ginger extract protects against cyclophosphamide (CP)-induced ovarian failure in rats. METHODS: Rats were distributed into four groups consisting of vehicle, CP, ginger, and CP + ginger. At the end of the treatment, all rats were killed under anesthesia to obtain ovarian tissues and blood samples for histological, molecular, and biochemical experiments. RESULTS: Our results indicated that ginger improves CP-caused histological changes in ovarian tissues and significantly restores serum hormonal abnormalities. Ginger also showed unique antioxidant, anti-inflammatory, and antiapoptotic properties in the ovarian tissues of CP-induced rats. Further, our findings indicated that ginger might activate the Nrf2 and SIRT and inhibit the PI3K/AKT pathway in the ovaries of CP-treated rats. In conclusion, ginger was found to protect against CP-caused ovarian toxicity in rats. CONCLUSION: The protective impacts of ginger may mediate, at least partly, by alleviating the oxidant state, inhibiting pro-inflammatory conditions, and exhibiting antiapoptotic activities.

Reduction of Doxorubicin-Induced Cardiotoxicity by Co-Administration of Smart Liposomal Doxorubicin and Free Quercetin: In Vitro and In Vivo Studies.

Doxorubicin is one of the most effective chemotherapeutic agents; however, it has various side effects, such as cardiotoxicity. Therefore, novel methods are needed to reduce its adverse effects. Quercetin is a natural flavonoid with many biological activities. Liposomes are lipid-based carriers widely used in medicine for drug delivery. In this study, liposomal doxorubicin with favorable characteristics was designed and synthesized by the thin-film method, and its physicochemical properties were investigated by different laboratory techniques. Then, the impact of the carrier, empty liposomes, free doxorubicin, liposomal doxorubicin, and quercetin were analyzed in animal models. To evaluate the interventions, measurements of cardiac enzymes, oxidative stress and antioxidant markers, and protein expression were performed, as well as histopathological studies. Additionally, cytotoxicity assay and cellular uptake were carried out on H9c2 cells. The mean size of the designed liposomes was 98.8 nm, and the encapsulation efficiency (EE%) was about 85%. The designed liposomes were anionic and pH-sensitive and had a controlled release pattern with excellent stability. Co-administration of liposomal doxorubicin with free quercetin to rats led to decreased weight loss, creatine kinase (CK-MB), lactate dehydrogenase (LDH), and malondialdehyde (MDA), while it increased the activity of glutathione peroxidase, catalase, and superoxide dismutase enzymes in their left ventricles. Additionally, it changed the expression of NOX1, Rac1, Rac1-GTP, SIRT3, and Bcl-2 proteins, and caused tissue injury and cell cytotoxicity. Our data showed that interventions can increase antioxidant capacity, reduce oxidative stress and apoptosis in heart tissue, and lead to fewer complications. Overall, the use of liposomal doxorubicin alone or the co-administration of free doxorubicin with free quercetin showed promising results.

Using chitosan-stabilized, hyaluronic acid-modified selenium nanoparticles to deliver CD44-targeted PLK1 siRNAs for treating bladder cancer.

Aims: Achieving an effective biocompatible system for siRNAs delivery to the tumor site remains a significant challenge. Materials & methods: Selenium nanoparticles (SeNPs) modified by chitosan (CS) and hyaluronic acid (HA) were fabricated for PLK1 siRNAs (siPLK1) delivery to the bladder cancer cells. The HA-CS-SeNP@siPLK1 efficacy was evaluated using in vitro and in vivo models. Results: HA-CS-SeNP@siPLK1 was selectively internalized into T24 cells through clathrin-mediated endocytosis. Treatment with HA-CS-SeNP@siPLK1 successfully silenced the PLK1 gene, inhibited cell proliferation and induced cell cycle arrest in vitro. HA-CS-SeNP@siPLK1 could also inhibit tumor growth in vivo without causing systemic toxicity. Conclusion: Our results suggest that HA-CS-SeNPs may provide a good vehicle for delivering siPLK1 to the bladder tumor site.

siRNAs are small biomolecules shown as novel insights in cancer gene therapy because of their capability to silence target genes. However, achieving an effective biocompatible system for siRNA delivery to the tumor site remains a significant challenge. This work aimed to develop a nanoparticle-based delivery system consisting of selenium nanoparticles modified by chitosan and hyaluronic acid to sustain the release of siRNAs to bladder cancer cells. The results of this study demonstrated that this nanosystem successfully silenced the PLK1 gene and reduced the proliferation in vitro and in vivo. These findings suggest that hyaluronic acid-chitosan-selenium nanoparticles may open a new insight for targeted gene therapy for bladder cancer.

Fe3O4/Au/porous Au nanohybrid for efficient delivery of doxorubicin as a model drug.

Fe3O4/Au/porous Au nanohybrids being bi-functional nanoparticles with magnetic properties and high porosity, were synthesized and used for drug delivery. To achieve this purpose, after Fe3O4 nanoparticles synthesis, a gold layer coats them to increase their stability. Then, to improve the loading capacity of Fe3O4/Au nanoparticles, a shell of porous gold was synthesized on the Fe3O4/Au surface by creating an Ag-Au nanohybrid layer on Fe3O4/Au and dissolving the metallic silver atoms in HNO3 (0.01 M). The DLS results show that the synthesized nanohybrid has an average size of 68.0 ± 7.7 nm and a zeta potential of - 28.1 ± 0.2 mV. Finally, doxorubicin (DOX), as a pharmaceutical agent, was loaded onto the Fe3O4/Au/porous Au nanohybrids. The prepared nano-drug enhanced the therapeutic efficacy of DOX on MCF-7 cancer cells compared to the free DOX. These results confirmed a 1.5 times improvement in the antitumor activity of DOX-loaded Fe3O4/Au/porous Au nanohybrids.

Targeted delivery of 5-fluorouracil, miR-532-3p, and si-KRAS to the colorectal tumor using layer-by-layer liposomes.

Co-delivery of siRNA or miRNA with chemotherapeutic drugs into tumor sites is an attractive synergetic strategy for treating colorectal cancer (CRC) due to their complementary mechanisms. In the current work, a liposome nanoparticle (Huang et al., Cancer Metastasis Rev., 2018, 37, 173-187) coated by cationic chitosan (CS) using a controlled layer-by-layer (LbL) process was designed to deliver simultaneous si-KRAS, miRNA-532-3p, and 5-Fluorouracil (5-FU) into CRC cells. The LbL NPs exhibited a spherical structure with an average size of 165.9 nm and effectively protected si-KRAS and miRNA-532-3p against degradation by serum and nucleases. Interestingly, the LbL NPs were successfully entered into cells and efficiently promoted cytotoxicity and suppressed cancer cell migration and invasion. In vivo, the LbL NPs reduced tumor growth in SW480-tumor-bearing mice models. In conclusion, these results suggested that the LbL NPs co-loaded with 5-FU and miR-532-3p/si-KRAS might provide a promising potential strategy for inhibiting the malignant phenotypes of CRC cells.

Graphene oxide-l-arginine nanogel: A pH-sensitive fluorouracil nanocarrier.

Nowadays, putting forward an accurate cancer therapy method with minimal side effects is an important topic of research. Nanostructures, for their ability in controlled and targeted drug release on specific cells, are critical materials in this field. In this study, a pH-sensitive graphene oxide-l-arginine nanogel was synthesized to carry and release 5-fluorouracil. Optimized conditions using statistical analysis, based on the maximum relative viscosity of nanogel, were evaluated: 5.489 for the concentration of l-arginine and 2.404 for pH. The prepared nanogels were characterized using scanning electron microscope and transmission electron microscope images and Fourier-transform infrared spectroscopic analysis. Cytotoxicity was assessed using the sulforhodamine B (SRB) assay on MCF-7 breast cancer cells. The fluorouracil release was measured by the dialysis bag method, UV spectrophotometry, and fluorouracil calibration diagram. Results proved the successful controlled release of fluorouracil at pH 5.4 and the beneficial role of graphene-oxide- l-arginine- fluorouracil nanogel in eliminating cancer cells.

Novel microfluidic graphene oxide-protein amperometric biosensor for detecting sulfur compounds.

Sulfur compounds are essential for many industries and organisms; however, they cause serious respiratory problems in human beings. Therefore, determination of sulfur concentration is of paramount importance. The research approach in the field of detecting contaminants has led to smaller systems that provide faster and more effective ways for diagnosis purposes. In this study, a novel portable amperometric graphene oxide-protein biosensor platform is investigated. The main characteristic of this structure is the implementation of a microfluidic configuration. With albumin metalloprotein as the biorecognition element, graphene oxide was synthesized and characterized by transmission electron microscopy and Fourier-transform infrared spectroscopy (FTIR). Albumin protein was stabilized on the surface of graphene oxide by the application of the N-(3-dimethylamionpropyl)-N-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide method. The stabilization was confirmed by FTIR and electrochemistry analyses. The calibration curve of sulfur concentration was determined. When the graphene oxide-protein complex was stabilized by nephion on the surface of the microfluidic system, the response time reduced to 50 Sec, which is a relatively faster response among the similar studies and validated the significant effect of the microfluidic system. The nanosystem had an optimized pH of 7.4 and exhibited high sensitivity in determining sulfide. The results confirm that the portable graphene oxide-protein nanosystem has a fast and accurate response in detecting sulfide.