Nonlinear molecular dynamics of quercetin in Gynocardia odorata and Diospyros malabarica fruits: Its mechanistic role in hepatoprotection.

Liver performs number of critical physiological functions in human system. Intoxication of liver leads to accumulation of free radicals that eventually cause damage, fibrosis, cirrhosis and cancer. Carbon tetrachloride (CCl4) belongs to hepatotoxin is converted to a highly reactive free radical by cytochrome P450 enzymes that causes liver damage. Plant extracts derived quercetin has substantial role in hepatoprotection. This study highlights the possible mechanism by which quercetin plays significant role in hepatoprotection. HPLC analysis revealed the abundance of quercetin in the fruit extracts of Gynocardia odorata and Diospyros malabarica, were isolated, purified and subjected to liver function analysis on Wistar rats. Post quercetin treatment improved liver function parameters in the hepatotoxic Wistar rats by augmenting bilirubin content, SGOT and SGPT activity. Gene expression profile of quercetin treated rats revealed down regulation of HGF, TIMP1 and MMP2 expressed during CCl4 induction. In silico molecular mechanism prediction suggested that quercetin has a high affinity for cell signaling pathway proteins BCL-2, JAK2 and Cytochrome P450 Cyp2E1, which all play a significant role in CCl4 induced hepatotoxicity. In silico molecular docking and molecular dynamics simulation have shown that quercetin has a plausible affinity for major signaling proteins in liver. MMGBSA studies have revealed high binding of quercetin (ΔG) -41.48±11.02, -43.53±6.55 and -39.89±5.78 kcal/mol, with BCL-2, JAK2 and Cyp2E1, respectively which led to better stability of the quercetin bound protein complexes. Therefore, quercetin can act as potent inhibitor against CCl4 induced hepatic injury by regulating BCL-2, JAK2 and Cyp2E1.

Spontaneous and Induced Tumors in Germ-Free Animals: A General Review.

Cancer, bacteria, and immunity relationships are much-debated topics in the last decade. Microbiome's importance for metabolic and immunologic modulation of the organism adaptation and responses has become progressively evident, and models to study these relationships, especially about carcinogenesis, have acquired primary importance. The availability of germ-free (GF) animals, i.e., animals born and maintained under completely sterile conditions avoiding the microbiome development offers a unique tool to investigate the role that bacteria can have in carcinogenesis and tumor development. The comparison between GF animals with the conventional (CV) counterpart with microbiome can help to evidence conditions and mechanisms directly involving bacterial activities in the modulation of carcinogenesis processes. Here, we review the literature about spontaneous cancer and cancer modeling in GF animals since the early studies, trying to offer a practical overview on the argument.

Tumour Progression and Spontaneous Regression in the Lewis Rat Sarcoma Model.

Spontaneous regression of tumours is a fascinating phenomenon rarely observed in oncological patients. We used a Lewis rat sarcoma model in which subcutaneous tumours developed after inoculation of the R5-28/clone C4 cells. Rats with tumour progression showed splenomegaly and anaemia. Tumour growth was associated with leucocytosis, granulocytosis, decrease in lymphocyte and CD161(+) population in peripheral blood and increase in serum MCP1 concentration. Animals with spontaneous regression of tumours initially showed an increase in white blood cells number and proportion of granulocytes. Between the 42nd and 49th day, however, values of these parameters dropped in correlation with reduction of tumour size. In spontaneously regressed tumours, vascularization was higher and on the contrary, progressive tumours had more necrotic areas with a high number of infiltrating granulocytes. In conclusion, progression and spontaneous regression of tumours in the Lewis rat sarcoma model is associated with distinct changes in populations of blood cells and immune cells which participate in these completely different processes of tumourigenesis.

Tumor progression is associated with increasing CD11b+ cells and CCL2 in Lewis rat sarcoma.

Tumor models are essential for basic anticancer research and development of novel therapies. In this study, we used a rat sarcoma model in which subcutaneous tumor develops after D6 cell inoculation. The aim of the current study was to analyze changes in haematological parameters, immune cell sub-populations and cytokine profiling during tumor growth, after tumor excision and after second inoculation of D6 cells. Tumor progression was found to be associated with an increased number of leukocytes and increased proportion of CD11b+ cells in peripheral blood. Serum concentration of chemokine (c-c motif) ligand 2, L-selectin and intra cellular adhesion molecule-1 also increased with growing tumor. However, the proportion of CD4+, CD8+ and MHC II+ cells decreased with growth of tumors. After tumor excision, all these parameters returned to pre-inoculation levels and did not change even after a second inoculation of D6 cells. Moreover, absence of secondary tumors after second inoculation of D6 cells gives an insight into development of antitumor immunity stimulated by primary tumor.