Indoleamine 2,3-dioxygenase: As a potential prognostic marker and immunotherapeutic target for hepatocellular carcinoma

Tumor cells induce an immunosuppressive microen-vironment which leads towards tumor immune escape. Understanding the intricacy of immunomodulation by tumor cells is essential for immunotherapy. Indoleamine 2,3-dioxygenase(IDO) is an immunosuppressive enzyme which mediates tumor immune escape in various cancers including hepatocellular carcinoma(HCC). IDO up-regulation in HCC may lead to recruitment of regulatory T-cells into tumor microenvironment and therefore inhibit local immune responses and promote metastasis. HCC associated fibroblasts stimulate natural killer cells dysfunction through prostaglandin E2 and subsequently IDO promotes favorable condition for tumor metastasis. IDO up-regulation induces immuno-suppression and may enhance the risk of hepatitis C virus and hepatitis B virus induced HCC. Therefore, IDO inhibitors as adjuvant therapeutic agents may have clinical implications in HCC. This review proposes future prospects of IDO not only as a therapeutic target but also as a prognostic marker for HCC.

Separation and Identification of Flavonoids from Fistular Onion Stalk(Allium fisturosum L.var.Caespitosum Makio)

The chemical constituents of fistular onion stalk obtained by supercritical CO2 extraction were separated and purified by silica gel and sephadex LH-20 gel column chromatography and the preparative TLC method and four flavonoids were obtained. On the basis of the spectral data, they were structurally identified as （＋）-catechin, （-）-epieatechin, astragalin, and 3-O-β-D（2-O-β-D-glu- copyranosyl）-glucopyranosides of kaempferol.

Olfactory ensheathing cells for spinal cord repair: crucial differences between subpopulations of the glia

OECs for spinal cord repair： Is repairing the iniured spinal cord by olfactory ensheathing cell （OEC） transplantation pos- sible？ A recent human trial in which a paralysed man regained some function after transplantation of partially purified OECs suggests that this therapy may be a successful approach （Ta- bakow et al., 2014）. In another human trial in which olfactory mucosa lamina propria was transplanted, patients recovered some motor and sensory function （Wang et al., 2015）. While these results show promise, it is clear that improvements are needed to provide patients with increased functional output. Strategies to improve the therapeutic use of OECs may include improving the purification of the OECs used for transplantation, using them in combination with growth factors to combat the inhibitory environment and improve anon growth, the use of nerve bridges, advanced physiotherapy and the use of exo- skeleton robotics to reinforce functional connections. Of all these approaches, it is probably is primarily addressed to ensure crucial that the purity of OECs consistency in outcomes.

Radial glia interact with primary olfactory axons to regulate development of the olfactory bulb

The developing olfactory system - merging of the periph- eral and central nervous systems： The olfactory system is responsible for the sense of smell and is comprised of a complex topographic map that regenerates throughout life. In rodents each olfactory sensory neuron expresses one of N 1,300 odorant receptors with the neurons being distributed mosaically within the epithelium. The axons of the sensory neurons do not maintain near-neighbour relationships and instead project to disparate topographic targets in the olfac- tory bulb within the central nervous system. The develop- ment of the targets relies on the intermingling of the sensory axons with the interneurons, glia and second order neurons of the olfactory bulb. Thus the formation of the olfactory system involves the coordinated integration of the axons of the peripheral olfactory sensory neurons with the cells of the olfactory bulb.

Extensions of PDZ domains as important structural and functional elements

‘Divide and conquer’has been the guiding strategy for the study of protein structure and function.Proteins are divided into domains with each domain having a canonical structural definition depending on its type.In this review,we push forward with the interesting observation that many domains have regions outside of their canonical definition that affect their structure and function;we call these regions‘extensions’.We focus on the highly abundant PDZ(PSD-95,DLG1 and ZO-1)domain.Using bioinformatics,we find that many PDZ domains have potential extensions and we developed an openly-accessible website to display our results(http://bcz102.ust.hk/pdzex/).We propose,using well-studied PDZ domains as illustrative examples,that the roles of PDZ extensions can be classified into at least four categories:1)protein dynamics-based modulation of target binding affinity,2)provision of binding sites for macro-molecular assembly,3)structural integration of multi-domain modules,and 4)expansion of the target ligand-binding pocket.Our review highlights the potential structural and functional importance of domain extensions,highlighting the significance of looking beyond the canonical boundaries of protein domains in general.

Evaluation of fermentation conditions triggering increased antibacterial activity from a near-shore marine intertidal environment-associated Streptomyces species

A near-shore marine intertidal environment-associated Streptomyces isolate(USC-633)from the Sunshine Coast Region of Queensland,Australia,cultivated under a range of chemically defined and complex media to determine optimal parameters resulting in the secretion of diverse array of secondary metabolites with antimicrobial properties against various antibiotic resistant bacteria.Following extraction,fractioning and re-testing of active metabolites resulted in persistent antibacterial activity against Escherichia coli(Migula)(ATCC 13706)and subsequent Nuclear Magnetic Resonance(NMR)analysis of the active fractions confirmed the induction of metabolites different than the ones in fractions which did not display activity against the same bacterial species.Overall findings again confirmed the value of One StraineMany Compounds(OSMAC)approach that tests a wide range of growth parameters to trigger bioactive compound secretion increasing the likelihood of finding novel therapeutic agents.The isolate was found to be adaptable to both marine and terrestrial conditions corresponding to its original nearshore marine intertidal environment.Wide variations in its morphology,sporulation and diffusible pigment production were observed when different growth media were used.

Discovery of tanshinone derivatives with anti-MRSA activity via targeted bio-transformation

Two potent anti-MRSA tanshinone glycosides(1 and 2)were discovered by targeted microbial biotransformation,along with rapid identification via MS/MS networking.Serial reactions including dehydrogenation,demethylations,reduction,glycosylation and methylation have been observed after incubation of tanshinone IIA and fungus Mucor rouxianus AS 3.3447.In addition,tanshinosides B(2)showed potent activities against serial clinical isolates of oxacillin-resistant Staphylococcus aureus with MIC values of 0.78 mg/mL.This is the first study that shows a significant increase in the level and activities of tanshinone glycosides relative to the substrate tanshinone IIA.