Contribution of CD24 polymorphisms to autoimmune disease: A meta-analysis.

PURPOSE: To determine the relationship between two CD24 polymorphisms, rs8734/rs52812045 and rs3838646, and autoimmune disease. DESIGN: Meta-analysis. METHODS: The Medline, EMBASE, Web of Science, and Cochrane Library databases were searched for studies reporting the association between CD24 polymorphisms and autoimmune disease. Two of the authors selected eligible studies and extracted and analyzed the data independently. RESULTS: Compared with carriers of the C allele (CC, CT, CT+CC), individuals homozygous for the T allele (TT) and heterozygous (CT+TT) at rs8734/rs52812045 have a higher incidence of autoimmune disease, whereas rs3838646 is not associated with autoimmune disease. Subgroup analysis found an increased risk of multiple sclerosis with the TT vs. CC, TT vs. CT, and TT vs. CC+CT alleles. CONCLUSION: The CD24 polymorphism rs8734/rs52812045 contributes to the development of autoimmune disease.

The association of CD28 polymorphism, rs3116496, with Cancer: A meta-analysis.

OBJECTIVE: To determine the relationship between CD28 polymorphisms, rs3116496, and cancer. DESIGN: Meta-analysis. METHODS: PubMed, EMBASE, Web of Science, and Cochrane library databases were searched to identify studies reporting the association between CD28 polymorphism and cancer. Two authors selected identified studies, extracted, and analyzed the data independently. RESULTS: Individuals carrying a T allele (TT homozygotes and TT+TC heterozygotes) at rs3116496 had a lower incidence of cancer than carriers of a C allele. Subgroup analysis showed that this association held true for Asians, but not Europeans. CONCLUSION: CD28 polymorphism, rs3116496, contributes to cancer susceptibility in the case of multiple cancers.

Identification of arylsulfonamides as ExoU inhibitors.

ExoU is a potent virulence factor of Pseudomonas aeruginosa and is considered a potential therapeutic target. In order to discover novel ExoU inhibitors, we screened an in-house chemical library utilizing a yeast-based screening system. Some sulfonamides displayed significant activity without nonspecific cytotoxicity. We describe a series of sulfonamides as novel ExoU inhibitors, along with a brief structure-activity relationship.

Macro and small over micro: macromolecules and small molecules that regulate microRNAs.

Given the correlation between the deregulation of specific miRNAs and disease onset, it is critical to identify miRNA regulators that effectively control miRNAs involved in the pathogenesis of target diseases. This review provides the latest update on oligonucleotide- and small-molecule-based miRNA regulators, and discusses assays developed to screen for small-molecule regulators.

MicroRNA-targeting therapeutics for hepatitis C.

MiR-122 is a liver-specific microRNA (miRNA) that plays a pivotal role in regulating hepatic functions such as lipid metabolism and stress response. The observation that hepatitis C virus (HCV) could only replicate in miR-122-positive hepatocytes led to the discovery that miR-122 is essential for HCV replication, and miR-122 is now one of the crucial host factors for anti-HCV therapy. Currently, the most advanced miR-122 targeting therapy is SPC3649 (miravirsen), a locked nucleic acid-modified oligonucleotide antagonizing miR-122. This review serves to provide information on the discovery and development of SPC3649, the first miRNA-targeted drug to enter human clinical trials, and introduce other miR-122-targeting therapeutics being developed for hepatitis C.

Effects of prophylactic hematopoietic colony stimulating factors on stem cell transplantations: meta-analysis.

Hematopoietic growth factors are often given for prevention of febrile neutropenia (FN), infections, and other complications by hastening neutrophil recovery in the treatment of malignancies after high dose chemotherapy (HDCT). Although several meta-analyses have already demonstrated beneficial effects of prophylactic granulocyte colony-stimulating factors (G-CSF) administration, the effects of G-CSF have not been confirmed in cancer patients receiving stem cell transplantation (SCT) after HDCT. Therefore, we performed a statistical combination of controlled clinical trials to investigate the efficacy of prophylactic use of G-CSF in preventing the neutropenic complications associated with SCT following HDCT in cancer patients. We searched PubMed to identify potentially relevant references and finally selected seven randomized controlled trials that met all of the eligibility criteria. Our meta-analysis demonstrated that prophylactic G-CSF reduced the risk of documented infections and time to hematologic recovery manifested by days to absolute neutrophil count (ANC) ≥ 0.5 × 10(9)/L, days to ANC ≥ 1.0 × 10(9)/L, and days to platelets ≥ 20 × 10(9)/L in SCT patients with cancer following HDCT. The G-CSF treated group also showed a decrease in the length of hospital stay. However, there was no difference between G-CSF treatment group and placebo group in regard to all-cause mortality, infection-related mortality, grade 2∼4 acute graft-versus-host-disease, and episode of fever.

Filaggrin knockdown and Toll-like receptor 3 (TLR3) stimulation enhanced the production of thymic stromal lymphopoietin (TSLP) from epidermal layers.

Keratinocytes constitute the first-line barrier against exogenous antigens and contain Toll-like receptors (TLRs), which function as pattern-recognition molecules to activate antimicrobial innate immune responses. In an effort to ascertain whether or not filaggrin (filament-aggregating protein) expression affected the TLR-mediated responses of keratinocytes, we transfected filaggrin siRNA into HaCaT human keratinocyte cells and determined that thymic stromal lymphopoietin (TSLP) and IL-6 secretion were increased by poly(I:C) stimulus. Additionally, TSLP expression is increased in filaggrin knockdown as well as TLR3 stimulation in reconstituted human epidermal layers. Therefore, the findings of this study show that reduced filaggrin levels may influence innate immune responses via TLR stimuli and may contribute to the pathogenesis of inflammatory skin disease via TSLP expression.