Cordyceps Mushroom: a Potent Anticancer Nutraceutical

The Cordyceps mushrooms have a long history as medicinal fungi. In Traditional Chinese Medicine, Cordyceps have been used to treat several conditions including cancers for thousand of years. Extracts from both mycelium and fruiting bodies of C. sinensis, C. militaris and other Cordyceps species showed significant anticancer activities by various mechanisms such as, modulating immune system and inducing cell apoptosis. Some polysaccharide components and cordycepin (3\u27 -deoxyadenosine) have been isolated from C. sinensis and C. militaris, which acted as potent anticancer components. This review article aims to further elucidate the importance of Cordyceps mushrooms by summarizing the findings of some of the important research works concerning possible mechanism of anticancer activity of this mushroom

Effects of a particular heptapeptide on the IFN-α-sensitive CML cells

Abstract: Using the phage display biopanning technique, we have previously identified a heptapeptide KLWVIPQ which specifically bind to the surface of the IFN-α sensitive but not the IFN-α-resistant CML cells. The effects of this heptapeptide to the IFN-α-sensitive CML cells were investigated in the present study. IFN-α-sensitive KT-1/A3 and IFN-α-resistant KT-1/A3R CML cells were transfected by pEGFP KLWVIPQ expression vector and/or induced by IFN-α. WST-1 cell proliferation assay, flow cytometry and western blotting were performed to determine the effects of this heptapeptide and/or IFN-α on CML cells. The viability of the KT-1/A3 cells w as inhibited and apoptosis was induced by either expression of the heptapeptide KLWVIPQ or IFN-α treatment with concurrent up-regulation of P53 and down-regulation of P210bcr/abl. However, these effects were not observed in the IFN-α-resistant KT-1/A3R cells. These results suggest that the heptapeptide KLWVIPQ shares a similar mechanism w ith IFN-α in the regulat ion of CML cell growth and apoptosis, implying that the heptapeptide KLWVIPQ could be a novel target to go further into mechanisms of IFN-α sensitivity and/or resistance in CML

ISG15 inhibits IFN- a -Resistant liver cancer cell growth

Hepatocellular carcinoma (HCC) is one of the most prevalent tumors worldwide. Interferon-a (IFN-a) has been widely used in the treatment of HCC, but patients eventually develop resistance. ISG15 ubiquitin-like modifier (ISG15) is a ubiquitin-like protein transcriptionally regulated by IFN-a which shows antivirus and antitumor activities. However, the exact role of ISG15 is unknown. In the present study, we showed that IFN-a significantly induced ISG15 expression but failed to induce HepG2 cell apoptosis, whereas transient overexpression of ISG15 dramatically increased HepG2 cell apoptosis. ISG15 overexpression increased overall protein ubiquitination, which was not observed in cells with IFN-a-induced ISG15 expression, suggesting that IFN-a treatment not only induced the expression of ISG15 but also inhibited ISG15-mediated ubiquitination. The tumor suppressor p53 and p21 proteins are the key regulators of cell survival and death in response to stress signals such as DNA damage. We showed that p53 or p21 is only up regulated in HepG2 cells ectopically expressing ISG15, but not in the presence of IFN-a-induced ISG15. Our results suggest that ISG15 overexpression could be developed into a powerful gene-therapeutic tool for treating IFN-a-resistant HCC. © 2013 Xin-xing Wan et al

Tripartite motif containing 28 (TRIM28) promotes breast cancer metastasis by stabilizing TWIST1 protein.

TRIM28 regulates its target genes at both transcriptional and posttranscriptional levels. Here we report that a TRIM28-TWIST1-EMT axis exists in breast cancer cells and TRIM28 promotes breast cancer metastasis by stabilizing TWIST1 and subsequently enhancing EMT. We find that TRIM28 is highly expressed in both cancer cell lines and advanced breast cancer tissues, and the levels of TRIM28 and TWIST1 are positively correlated with the aggressiveness of breast carcinomas. Overexpression and depletion of TRIM28 up- and down-regulates the protein, but not the mRNA levels of TWIST1, respectively, suggesting that TRIM28 upregulates TWIST1 post-transcriptionally. Overexpression of TRIM28 in breast cancer cell line promotes cell migration and invasion. Knockdown of TRIM28 reduces the protein level of TWIST1 with concurrent upregulation of E-cadherin and downregulation of N-cadherin and consequently inhibits cell migration and invasion. Furthermore, Immunoprecipitation and GST pull-down assays demonstrated that TRIM28 interacts with TWIST1 directly and this interaction is presumed to protect TWIST1 from degradation. Our study revealed a novel mechanism in breast cancer cells that TRIM28 enhances metastasis by stabilizing TWIST1, suggesting that targeting TRIM28 could be an efficacious strategy in breast cancer treatment

Genetic Identification and Molecular Modeling Characterization Reveal a Novel PROM1 Mutation in Stargardt4-like Macular Dystrophy

Stargardt disease-4 (STGD4) is an autosomal dominant complex, genetically heterogeneous macular degeneration/dystrophy (MD) disorder. In this paper, we used targeted next generation sequencing and multiple molecular dynamics analyses to identify and characterize a disease-causing genetic variant in four generations of a Chinese family with STGD4-like MD. We found a novel heterozygous missense mutation, c.734T\u3eC (p.L245P) in the PROM1 gene. Structurally, this mutation most likely impairs PROM1 protein stability, flexibility, and amino acid interaction network after changing the amino acid residue Leucine into Proline in the basic helix-loop-helix leucine zipper domain. Molecular dynamic simulation and principal component analysis provide compelling evidence that this PROM1 mutation contributes to disease causativeness or susceptibility variants in patients with STGD4-like MD. Thus, this finding defines new approaches in genetic characterization, accurate diagnosis, and prevention of STGD4-like MD

A Highly Pathogenic Strain of Staphylococcus sciuri Caused Fatal Exudative Epidermitis in Piglets

Staphylococcus sciuri are important human pathogens responsible for endocarditis, peritonitis, septic shock, urinary tract infection, pelvic inflammatory disease and wound infections. However, little information is known regarding the pathogenicity of S. sciuri to animals. From the pericardial fluid of a diseased piglet with exudative epidermitis (EE), we isolated a strain of Staphylococcus in pure culture. Surprisingly, this isolate was a member of S. sciuri rather than S. hyicus as identified by its biochemical traits and also by analysis of 23S ribosomal DNA using Internal Transcribed Spacer PCR. In addition, inoculation of newborn piglets with 1×10(10) CFU of the isolate by oral feeding or intra-muscular injection successfully reproduced EE in piglets, which suggested that the oral intake of the pathogen by the animals is one of the major routes of exposure. These unexpected findings prioritized S. sciuri as important zoonotic agents, which may have ramifications for human medicine

The Functions of ISG15 Ubiquitin-like Modifier and its Modifier Enzymes

Interferon\|stimulated gene 15 　encoded protein (ISG15) was identified as one of the first ubiquitin\|like modifier that induced by interferons. Numerous ISG15\|target proteins have been identified in tumors and virus\|infected cells. Multiple lines of evidence suggest that ISG15 plays important roles in the innate immune pathways and in cancer development. We focus on the structure and biochemical features of ISG15, as well as the mechanisms of the ISGylation of target proteins assisted with ISG15 modifier enzymes. The anti\|viral and anti\|cancer activities of ISG15 and its modifier enzymes are also discussed

Antioxidant Enzymes and Cancer

Although oxidation is the most common biological and energy producing reaction, oxidative stress is harmful to cell, because the products of oxidation such as free radicals and peroxides damage the cellular components, causing several diseases. Damage in DNA is responsible for cancer formation and progression. However, several enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase etc. act as antioxidants to influence oxidative stress. Polymorphisms in these enzymes are supposed to be associated with DNA damage and subsequently the individual’s risk of cancer susceptibility. This review article aims to further elucidate the relationship between antioxidant enzymes and cancers by summarizing the findings of some of the important study concerning expression levels and genetic polymorphisms of antioxidant enzymes in cancer patients