Abstract:Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines, ISCOMs (immunostimulating complexes), Freund's complete adjuvant, Freund's incomplete adjuvant, alums, bacterial toxins etc., are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed.

Soluble amyloid β-protein (Aβ) oligomers, the main neurotoxic species, are predominantly formed from monomers through a fibril-catalyzed secondary nucleation. Herein, we virtually screened an in-house library of natural compounds and discovered brazilin as a dual functional compound in both Aβ42 fibrillogenesis inhibition and mature fibril remodeling, leading to significant reduction in Aβ42 cytotoxicity. The potent inhibitory effect of brazilin was proven by an IC50 of 1.5 ± 0.3 μM, which was smaller than that of (−)-epigallocatechin gallate in Phase III clinical trials and about one order of magnitude smaller than those of curcumin and resveratrol. Most importantly, it was found that brazilin redirected Aβ42 monomers and its mature fibrils into unstructured Aβ aggregates with some β-sheet structures, which could prevent both the primary nucleation and the fibril-catalyzed secondary nucleation. Molecular simulations demonstrated that brazilin inhibited Aβ42 fibrillogenesis by directly binding to Aβ42 species via hydrophobic interactions and hydrogen bonding and remodeled mature fibrils by disrupting the intermolecular salt bridge Asp23-Lys28 via hydrogen bonding. Both experimental and computational studies revealed a different working mechanism of brazilin from that of known inhibitors. These findings indicate that brazilin is of great potential as a neuroprotective and therapeutic agent for Alzheimer's disease.

The medical and economic importance of ticks has long been recognized due to their ability to transmit diseases to humans and animals. Ticks cause great economic losses to livestock, and adversely affect livestock hosts in several ways. Loss of blood is a direct effect of ticks acting as potential vector for haemo-protozoa and helminth parasites. Blood sucking by large numbers of ticks causes reduction in live weight and anemia among domestic animals, while their bites also reduce the quality of hides. However, major losses caused by ticks are due to their ability to transmit protozoan, rickettsial and viral diseases of livestock, which are of great economic importance world-wide. There are quite a few methods for controlling ticks, but every method has certain shortcomings. The present review is focused on ticks importance and their control.

The MYC oncogene is overexpressed in hepatocellular carcinoma (HCC) and has been associated with widespread microRNA (miRNA) repression; however, the underlying mechanisms are largely unknown. Here, we report that the c‐Myc oncogenic transcription factor physically interacts with enhancer of zeste homolog 2 (EZH2), a core enzymatic unit of polycomb repressive complex 2 (PRC2). Furthermore, miR‐101, an important tumor‐suppressive miRNA in human hepatocarcinomas, is epigenetically repressed by PRC2 complex in a c‐Myc‐mediated manner. miR‐101, in turn, inhibits the expression of two subunits of PRC2 (EZH2 and EED), thus creating a double‐negative feedback loop that regulates the process of hepatocarcinogenesis. Restoration of miR‐101 expression suppresses multiple malignant phenotypes of HCC cells by coordinate repression of a cohort of oncogenes, including STMN1, JUNB, and CXCR7, and further increases expression of endogenous miR‐101 by inhibition of PRC2 activation. In addition, co‐overexpression of c‐Myc and EZH2 in HCC samples was closely associated with lower expression of miR‐101 (P < 0.0001) and poorer prognosis of HCC patients (P < 0.01). Conclusions: c‐Myc collaborates with EZH2‐containing PRC2 complex in silencing tumor‐suppressive miRNAs during hepatocarcinogenesis and provides promising therapeutic candidates for human HCC. (Hepatology 2014;59:1850–1863)