DMA, a Small Molecule, Increases Median Survival and Reduces Radiation-Induced Xerostomia via the Activation of the ERK1/2 Pathway in Oral Squamous Cell Carcinoma.

Survival, recurrence, and xerostomia are considerable problems in the treatment of oral squamous carcinoma patients. In this study, we investigated the role of DMA (5-(4-methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxyphenyl)5″benzimidazoyl]benzimidazole) as a salivary gland cytoprotectant in a patient-derived xenograft mouse model. A significant increase in saliva secretion was observed in the DMA-treated xenograft compared to radiation alone. Repeated doses of DMA with a high dose of radiation showed a synergistic effect on mice survival and reduced tumor growth. The mean survival rate of tumor-bearing mice was significantly enhanced. The increased number of Ki-67-stained cells in the spleen, intestine, and lungs compared to the tumor suggests DMA ablates the tumor but protects other organs. The expression of aquaporin-5 was restored in tumor-bearing mice injected with DMA before irradiation. The reduced expression of αvß3 integrin and CD44 in DMA alone and DMA with radiation-treated mice suggests a reduced migration of cells and stemness of cancer cells. DMA along with radiation treatment results in the activation of the Ras/Raf/MEK/ERK pathway in the tumor, leading to apoptosis through caspase upregulation. In conclusion, DMA has strong potential for use as an adjuvant in radiotherapy in OSCC patients.

Synthesis of salicylic acid phenylethyl ester (SAPE) and its implication in immunomodulatory and anticancer roles.

Salicylic acid phenylethyl ester (SAPE) was synthesized by Zn(OTf)2-catalyzed selective esterification of salicylic acid and phenylethyl alcohol and studied for its role as an immunomodulatory and anticancer agent. Low toxicity and favorable physical, Lipinski-type, and solubility properties were elucidated by ADME-tox studies. Molecular docking of SAPE against COX-2 revealed favorable MolDockscore, rerank score, interaction energy, internal pose energy, and hydrogen bonding as compared to ibuprofen and indomethacin. An average RMSD of ~ 0.13 nm for the docked complex with stable dynamic equilibrium condition was noted during the 20 ns MD simulation. A low band gap predicting a strong binding affinity at the enzyme's active site was further predicted by DFT analysis. The ester caused a reduction in the percentage of erythrocyte hemolysis and was shown to be non-cytotoxic against human lymphocytes, CaCo-2, and HepG-2 cells by the MTT assay. Moreover, it's in vitro efficacy in inhibiting COX-2 enzyme under both LPS stimulated intestinal cells and direct sequestration assays was found to be higher than salicylic acid and indomethacin. The anticancer activity of SAPE was tested on the breast cancer cell line MCF-7, and potential efficacy was exhibited in terms of decreased cell viability. Flow cytometry analysis exhibited the arrest of the cell cycle at G1/G0 and S phases, during which induction of autophagic vesicle formation and decrease in mitochondrial membrane potential was observed owing to increased ROS production. Furthermore, at these phases, the onset of apoptosis along with DNA damage was also observed. Pre-treatment with SAPE in colitis-induced Wistar rats displayed low disease activity index and reduction in the extent of intestinal tissue disruption and lipid peroxidation. A marked increase of anti-oxidative enzymes viz., catalase, GGT, and GST, and a decrease of pro-inflammatory cytokines IL-6 and TNF-α in the intestinal tissue extracts of the treated groups was noted. The results of this study have sufficient credence to support that the synthesised ester (SAPE) be considered as an anti-oxidative and anti-inflammatory compound with therapeutic potential for the effective management of cancer.

Biogenic nanosized gold particles: Physico-chemical characterization and its anticancer response against breast cancer.

With the advancement of nanotechnology, the nano-sized particles make an imprint on our daily lives.The present investigation revealed that biomolecules present in seed exudates of Vigna radiata are responsible for the synthesis of AuNPs, confirmed by the routine characterization techniques. Anticancer efficacy showed by AuNPs might be due to the release of phytochemicals in the exudate which is being adsorbed on the surface of AuNPs referencing their anticancer efficacy against the tested breast cancer cell lines. Inhibition of clonogenicity and cell cycle arrest at G2/M phase then apoptosis of AuNPs was also observed, but found nontoxic to the human PBMC cells which further confirms its biocompatible property Among the various physicochemical study, present AuNPs shows unique information, they show photoluminescent property which may be used for bioimaging purposes. However, further molecular analysis needs to be explored to understand the underlying mechanism for therapeutic and biomedical application.

Oxidative stress mediated hepatotoxicity induced by ZNP and modulatory role of fruit extract on male Wistar rat.

Zinc oxide nanoparticles (ZNP) are being used in various fields viz cosmetics industry as UV protectants, in the food packaging industry due to their anti-bacterial properties, in agriculture as micronutrients, etc. Increased applications of ZNPs in our day to day life, leading to the contamination of the surrounding environment posing a direct or indirect health risk. Various reports suggest that fruits and vegetables are a rich source of phytochemicals having antioxidant properties which help in neutralizing ROS generated on metal toxicity of the body. The present study focuses to study the ameliorative effect of apple (Pyrus malus) extract (E) on ZNP induced toxicity. Therefore, animals were grouped, six in each, exposed to various doses of ZNP (50 and 250 mg/kg), ZNP (50 and 250 mg/kg)+E. The studied parameters was: food intake, water intake, antioxidants assay, zinc accumulation, and histological alterations and was compared to control. Investigation revealed that ZNP induces toxicity as revealed by the alteration in the studied parameter, whereas those exposed to ZNP along with Pyrus malus fruit extract try to reduce the toxicity induced by nanoparticles but at low doses only. This ameliorative effect of fruit extract might be due to the presence of antioxidants scavenging the free radicals generated by ZNPs suggesting that antioxidant-rich fruit may have a protective role and have the potential to reduce the nanoparticles mediated oxidative stress.

Author Correction: Transcript expression profiling in two contrasting cultivars and molecular cloning of a SKP-1 like gene, a component of SCF-ubiquitin proteasome system from mungbean Vigna radiate L.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Assessment of intermittent exposure of zinc oxide nanoparticle (ZNP)-mediated toxicity and biochemical alterations in the splenocytes of male Wistar rat.

Nanoparticles are being used extensively and found in applications to various fields ranging from agriculture to electronic devices, diagnosis to drug delivery, and cosmetics to food packaging. Increasing usage of engineered nanomaterials (ENM) raises potential concern for human health as well as to the environment. The present study aims to explore the effects of intermittent intraperitoneal exposure of ZNP on the spleen of male Wistar rat. Animals were divided into three groups, control and ZNP-treated groups (50 mg/kg and 250 mg/kg body weight), six in each group. Experimental animals were treated with different doses of ZNP once a week for 4 weeks, whereas control groups received water. After 28 days of exposure, animals were sacrificed, spleen tissue was excised, and various parameters such as hematological, genotoxicity, antioxidants, and histopathological were studied for changes in spleen if any. Results showed that ZNP exposure manages to induce alteration in various studied hematological parameters like neutrophils, platelets, and eosinophils which are found to increase significantly after the last treatment compared with the first treatment of ZNP. However, hemoglobin content, PCV, and MCV decrease with increasing dose of ZNP significantly in last treatment, when compared with the first treatment. DNA damage was observed in rats treated with a high dose of ZNPs compared with that in the control when analyzed through comet assay. Flow cytometric study was performed for better understanding of the underlying mechanism of the ZNP-mediated toxicity. From the present investigation, an increase in ROS production, a decrease in MMP, and increased apoptosis were exhibited. Further, altered antioxidant level (SOD, CAT, LDH, CYT P450, and CYT b5 r) has been observed in the studied splenic tissue, also histopathological changes observed in the rats exposed with high doses of ZNP. Therefore, ZNP may have the potential to induce a toxic effect even when exposed intermittently.