A natural flavonoid glucoside, icariin, regulates Th17 and alleviates rheumatoid arthritis in a murine model.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that causes deformity of the joints and physical disability. Icariin, a natural flavonoid glucoside isolated from plants in the Epimedium family, has been proven to have various pharmacological activities. A recent study showed that icariin suppressed cartilage and bone degradation in mice of collagen-induced arthritis. However, the mechanism needs to be further investigated. In our current study, we found that icariin reduced the arthritis score and the incidence of arthritis compared with that in mice treated with water. Icariin inhibits the expression of various osteoclastogenic markers, such as ß3 integrin, cathepsin K, and MMP9 in vitro. Icariin treatment in mice with CIA also resulted in less number of Th17 cells and decreased ratio of CD4(+)IL-17(+) cells. The alleviated arthritis score and incidence of arthritis and reduced serum levels of IgG2a induced by icariin were abolished with additional IL-17 administration. Furthermore, icariin inhibited STAT3 activation in T cells and STAT3 inhibitor resulted in decreased IL-17 production and alleviated RA. In conclusion, icariin decreases Th17 cells and suppresses the production of IL-17, which contributes to the alleviated rheumatoid arthritis, through the inhibition of STAT3 activation.

[Fusarium solani infection in a patient after allogeneic hematopoietic stem cell transplantation: case report and literature review].

OBJECTIVE: To study Fusarium solani infection as a complication in patients after allogeneic hematopoietic stem cell transplantation and to discuss the diagnosis and appropriate therapy. METHODS: Symptoms, physical examination, laboratory tests, computed tomographic (CT) scans, treatments and outcomes of Fusarium solani infection in a patient with acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation were retrospectively analyzed, and related literatures reviewed. RESULTS: The patient developed pulmonary infiltration and systemic multiple subcutaneous masses after allogeneic hematopoietic stem cell transplantation. Tissue biopsy smear showed a large number of hyphae and spores, and fungal culture grew Fusarium solani. The subcutaneous masses were incised and drained, while amphotericin B and voriconazole were administered, with granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for hematopoietic recovery. The patient was discharge after full recovery. CONCLUSION: Fusarium solani infection is a rare but fatal complication after allogeneic hematopoietic stem cell transplantation. Once the skin lesions or subcutaneous masses developed, tissue smear and culture should be done as soon as possible. Early diagnosis and effective treatment to recovery of the patient after allogeneic hematopoietic stem cell transplant. Moreover, the recovery of adequate neutrophil levels is the most important factor in the resolution of fusarial infection.

Emerging Methods for Efficient and Extensive Incorporation of Non-canonical Amino Acids Using Cell-Free Systems.

Cell-free protein synthesis (CFPS) has emerged as a novel protein expression platform. Especially the incorporation of non-canonical amino acids (ncAAs) has led to the development of numerous flexible methods for efficient and extensive expression of artificial proteins. Approaches were developed to eliminate the endogenous competition for ncAAs and engineer translation factors, which significantly enhanced the incorporation efficiency. Furthermore, in vitro aminoacylation methods can be conveniently combined with cell-free systems, extensively expanding the available ncAAs with novel and unique moieties. In this review, we summarize the recent progresses on the efficient and extensive incorporation of ncAAs by different strategies based on the elimination of competition by endogenous factors, translation factors engineering and extensive incorporation of novel ncAAs coupled with in vitro aminoacylation methods in CFPS. We also aim to offer new ideas to researchers working on ncAA incorporation techniques in CFPS and applications in various emerging fields.

Effect of pravastatin treatment on circulating adiponectin: a meta-analysis of randomized controlled trials.

OBJECTIVE: Pravastatin has been suggested to increase circulating adiponectin in humans. However, results of randomized controlled trials (RCTs) are inconsistent. We aimed to systematically evaluate the influence of pravastatin on circulating adiponectin in humans by performing a meta-analysis of RCTs. MATERIALS AND METHODS: Studies were identified via systematic searching of PubMed, Embase, and Cochrane's Library databases. A random effect model was used to pool the results. Meta-regression and subgroup analyses were applied to explore the source of heterogeneity. RESULTS: Eight RCTs with nine comparisons of 595 participants were included. Pravastatin treatment was associated with a significant increased level of circulating adiponectin as compared with controls (weighted mean difference [WMD] =0.63 µg/mL; 95% CI, 0.17-1.09 µg/mL; P=0.007) with moderate heterogeneity (I2=28%). These results were confirmed by meta-analysis of double-blinded placebo-controlled RCTs (WMD =0.82 µg/mL; P=0.01). Meta-regression analyses indicated that proportions of males in each study were positively correlated with the effect of pravastatin on adiponectin (coefficient: 0.015, P=0.03). Subgroup analyses confirmed that pravastatin significantly increased adiponectin in studies of males (WMD =1.41 µg/mL; P=0.008), but not in those of females (WMD =-0.04 µg/mL; P=0.94). CONCLUSION: Pravastatin treatment is associated with increased circulating adiponectin. Gender difference may exist regarding the effect of pravastatin treatment on adiponectin.

PAK4 confers the malignance of cervical cancers and contributes to the cisplatin-resistance in cervical cancer cells via PI3K/AKT pathway.

BACKGROUND: Multiple protein or microRNA markers have been recognized to contribute to the progression and recurrence of cervical cancers. Particular those, which are associated with the chemo- or radio-resistance of cervical cancers, have been proposed to be promising and to facilitate the definition for cervical cancer treatment options. METHODS: This study was designed to explore the potential prognosis value of p21-activated kinase (PAK)-4 in cervical cancer, via the Kaplan-Meier analysis, log-rank test and Cox regression analysis, and then to investigate the regulatory role of PAK4 in the cisplatin resistance in cervical cancer cells, via the strategies of both PAK4 overexpression and PAK4 knockout. RESULTS: It was demonstrated that PAK4 was upregulated in cervical cancer tissues, in an association with the cancer's malignance variables such as FIGO stage, lymph node or distant metastasis and the poor histological grade. The high PAK4 expression was also independently associated with poor prognosis to cervical cancer patients. Moreover, PAK4 confers cisplatin resistance in cervical cancer Hela or Caski cells. In addition, the PI3K/Akt pathway has been implicated in the PAK4-confered cisplatin resistance. And the PI3K/Akt inhibitor, LY294002, markedly deteriorated the cisplatin-mediated viability reduction of Hela or Caski cells, indicating the involvement of PI3K/Akt pathway in the cisplatin resistance in cervical cancer cells. CONCLUSION: This study has confirmed the significant prognostic role of PAK4 level in cervical cancer patients and has recognized the regulatory role in cervical cancer progression. Moreover, our study has indicated that PAK4 also confers the chemoresistance of cervical cancer cells in a PI3K/Akt-dependent way. Thus, our study indicates PAK4 as a promising marker for cervical cancer treatment.

Cardamonin exerts potent activity against multiple myeloma through blockade of NF-κB pathway in vitro.

NF-κB plays a major role in the pathology of multiple myeloma. Here, we intended to investigate the regulating effect of cardamonin on NF-κB in myeloma cells. We found for the first time that cardamonin suppressed viability and induced apoptosis of myeloma cells. Cardamonin activated caspase-3 and PARP and suppressed the expression of various anti-apoptotic proteins. We discovered that NF-κB was repressed by cardamonin through suppression of IKK expression and IκBα phosphorylation. Furthermore, the expression of NF-κB-regulated gene products ICAM-1, COX-2 and VEGF was down-regulated by cardamonin. These results suggest that cardamonin blocks NF-κB pathway in human multiple myeloma cells.