Targeting receptors of advanced glycation end products (RAGE): Preventing diabetes induced cancer and diabetic complications.

Cancer and diabetes are the two major disorders that affect a large proportion of the world's population. Results from multiple epidemiological studies have concluded that diabetes and cancer are linked, and diabetic patients live at much higher risks of developing cancer and diabetic complications at the later phase of disease. Inflammation is the central pathway that mediates both diabetic complications as well as cancer. Receptor of advanced glycation end products (RAGE) is a non-specific multi-ligand pattern recognition receptor that induces the inflammatory responses by binding with multiple ligands. RAGE and its ligands are upregulated in diabetes, inflammation and cancer. Advanced glycation end products (AGEs), high mobility group box protein-1 (HMGB1) and S100 proteins are the major RAGE ligands that contribute to these consequences and an increased release of RAGE ligands during diabetic conditions can be a possible mechanism leading to diabetic complications and cancer. Moreover, further release of RAGE ligands from cancer cells can be a possible mechanism behind the worsening of diabetic complications in diabetic cancer patients. Inhibition of RAGE signaling can prevent diabetic complications and cancer in diabetic patients and can be helpful in the management of worsening diabetic complications and cancer in diabetic cancer patients. Curcumin, Quercetin and Withaferin A are known to inhibit multiple molecular pathways that are involved in RAGE signaling. The combined effects of these molecules can be explored to achieve the complete inhibition of RAGE signaling in diabetic patients.

In vitro and in vivo anticancer efficacy potential of Quercetin loaded polymeric nanoparticles.

Quercetin (QCT) is a flavonoid, abundantly present in plants and has gained considerable interest for its antioxidant property and chemo preventive activity. Bioavailability of QCT is very low due to its poor aqueous solubility and instability. Researchers are working on the application of nanotechnology to target chemotherapeutic drugs to the tumour site. The aim of the present study was to develop quercetin loaded chitosan nanoparticles (QCT-CS NPs) with enhanced encapsulation efficiency and sustained release property. We prepared biocompatible NPs with small size (<200 nm) and encapsulation efficiency of 79.78%. In vitro drug release study exhibited a cumulative amount of 67.28% release of QCT over a period of 12 h. at pH 7.4. In vitro cytotoxicity assay showed significantly reduced IC50 value of QCT-CS NPs as compared to free QCT (p < 0.05). Intra venous treatment of QCT-CS NPs in tumour xenograft mice with A549 and MDA MB 468 cells exerted significant reduction of tumour volume in comparison to disease control groups (p < 0.05). Serum anti oxidant enzyme superoxide dismutase (SOD) level markedly increased in QCT-CS NPs treated tumour bearing mice than free QCT treated group. In summary, the recent investigations reported successful encapsulation of QCT in chitosan (CS) NPs to target the tumour microenvironment and exhibited enhanced efficacy of QCT-CS NPs in cancer therapy.

Anti-leukemic and anti-angiogenic effects of d-Limonene on K562-implanted C57BL/6 mice and the chick chorioallantoic membrane model.

BACKGROUND: d-Limonene, a monoterpene from citrus fruit has been found to have chemopreventive and chemotherapeutic activities in various types of cancers. In this study, we evaluated the in vivo effect of d-Limonene on a K562-induced model of chronic myeloid leukemia (CML) in C57BL/6 mice. METHOD: The tail vein injection model of K562 cells in immunocompromised C57BL/6 mice was developed and evaluated for characteristics of the disease. The mice were treated with d-Limonene and evaluated for haematological parameters. We also evaluated the effect of d-Limonene on angiogenesis using the chick chorioallantoic membrane (CAM) assay. RESULTS: In a complete blood count, a significant dose-dependent reduction in white blood cell, neutrophil and lymphocyte counts, but an elevation in red blood cell count and haemoglobin content was observed with d-Limonene treatment compared to the disease control or untreated group. In the CAM assay, d-Limonene produced a significant dose-dependent reduction in number of blood vessels in treatment groups compared to the vehicle-treated group. CONCLUSION: These studies suggest promising anti-leukemic and anti-angiogenic effects of d-Limonene in the treatment of CML.

Shigellosis murine model established by intraperitoneal and intranasal route of administration: a comparative comprehension overview.

Shigellosis, a major cause of mortality and morbidity, requires development of effective intervention strategy for which animal model mimicking human pathology is essential. Among various animal models for shigellosis, mice being more convenient have been used wherein intraperitoneal and intranasal routes are preferred. With the aim to comprehend the comparative pathophysiological indicators, we have examined relatively high and low dose of Shigella flexneri administered through intraperitoneal and intranasal routes in mice. Characterization of these two models along with the resulting pathophysiology of shigellosis adds to our understanding and offers suitable models appropriate to the objectives of the study.

Repositioning of anti-viral drugs as therapy for cervical cancer.

BACKGROUND: Increase in expression of eIF4E (Eukaryotic translation initiation factor 4E) protein is mediated by oncogenic proteins of Human Papilloma Virus (HPV). Increased expression of eIF4E plays an important role in HPV induced carcinogenesis. Ribavirin and Indinavir are known inhibitors of eIF4E activity. METHODS: The effect of the drugs on HeLa cells was assessed by in vitro assays including cell viability using MTT and Neutral red assay, apoptotic potential using Caspase-3, Caspase-8 and Caspase-9 activity assays and MMP-2 and MMP-9 secretion by determination of Gelatinase activity. The in vivo effect of Ribavirin treatment on tumor volume was assessed in human xenograft in immunocompromised C57BL/6 mice. RESULTS: In vitro analyses indicate that Ribavirin and Indinavir reduce viability of HeLa cells, induce apoptosis and decrease secretion of MMPs. Treatment with Ribavirin at a dose of 50mg/kg and 100mg/kg daily led to significant decrease in tumor volume in vivo. CONCLUSION: The study thus provides evidence that Ribavirin and Indinavir can be explored as therapy against HPV-18 induced cervical cancer.