Activity

Mechanistically, STS reduced activation of ERK1/2 and NF-κB in lungs of CS-exposed mice and CSE-treated 16HBE cells challenged with LPS. Taken together, STS protects against acute exacerbation of CS-induced lung injury, which provides a promising and potential therapeutic avenue to halt acute exacerbation of COPD. Dendritic cells (DCs) can initiate and regulate adaptive immunity depending on their maturation status. Many pharmacological and genetic means have been used in the generation of immature/tolerogenic DCs. However, the key factors controlling DCs tolerogenicity remain obscure. In this work, we demonstrated that AZD8055, an ATP-competitive inhibitor of mammalian target of rapamycin (mTOR), could also lead to a tolerogenic DC phenotype from several lines of evidence, such as suppression of T cell proliferation, promoting the generation of Tregs, and inducing allogeneic T cell apoptosis. Further studies using RNA-seq method identified 430, 1172 and 1436 differentially expressed genes (DEGs) between AZD-DCs vs. Control-DCs, LPS-DCs vs. Control-DCs, and AZD-DCs vs. LPS-DCs, respectively. The 5 most differentially expressed transcripts identified by RNA-seq expression profiles were validated by quantitative RT-PCR assays. NF-κB, p38MAPK, the ribosome and PPAR signaling pathways may be involved in the induction of tolerogenic DCs by AZD8055. Functional annotation showed some genes like MGL2, Cadherin-1, 4-1BB, RhoB and Pdpn, were quite different between AZD-DCs and Control-DCs/LPS-DCs, which might be related to the tolerogenic properties of AZD-DCs. Our work provided the potential underlying molecular mechanisms involved in the generation of tolerogenic DCs. Further functional characterization of individual target gene in DC tolerogenicity will help to develop novel therapeutic modalities in circumstances like transplant tolerance induction and autoimmunity. The novel chemical platform formed by the branched piperazine-2,5-dione peptide derivatives (2,5-diketopiperazines) for creating non-invasive biologically active peptidomimetics has been developed. A successful application of this approach to orally available hemostimulatory peptidomimetics was demonstrated for all-L cyclopeptide from the Glu-Trp-peptide family. In the 1980s, we have separated and characterized a number of dipeptides from the thymus homogenate. The most active peptide Glu-Trp has been studied and developed into the immunostimulating drug Thymogen. The inversion of the amino acid optical form endows the dipeptides with suppressor properties D-Glu-D-Trp-OH and D-Glu-(D-Trp)-OH, inhibit proliferation of hemopoietic progenitors in the intact bone marrow. Based on the peptide D-Glu-(D-Trp)-OH, the new immunosuppressive drug Thymodepressin has been prepared. In this work, we applied the platform mentioned above to the design and synthesis of orally active hemosuppressive Thymodepressin® analogs. The novel data for the hemosuppressor activity of the dipeptide D-Glu(D-Trp-OH)-OH and its cyclopeptide analogs are discussed. A new example is presented of a rare phenomenon when enantiomeric molecules demonstrate reciprocal (i.e., opposite) biological activities. Cellular crosstalk is an important mechanism in the pathogenesis of inflammatory disorders and cancers. One significant means by which cells communicate with each other is through the release of exosomes. Exosomes are extracellular vesicles formed by the outward budding of plasma membranes, which are then released from cells into the extracellular space. Many studies have suggested that microvesicles released by colon cancer cells initiate crosstalk and modulate the fibroblast activities and macrophage phenotypes. Interestingly, crosstalk among colon cancer cells, macrophages and cancer-associated fibroblasts maximizes the mechanical composition of the stromal extracellular matrix (ECM). Exosomes contribute to cancer cell migration and invasion, which are critical for colon cancer progression to metastasis. The majority of the studies on colorectal cancers (CRCs) have focused on developing exosomal biomarkers for the early detection and prediction of CRC prognosis. This study highlights the crosstalk among colon cancer-derived exosomes, macrophage phenotypes and fibroblasts during colon cancer metastasis. V.This study analyses the effects of exposure to tropical storms and hurricanes during pregnancy on children’s anthropometric measures taken within the first five years of life. We merge destruction indexes calculated at the district level with 13 yearly rounds of household level surveys from Jamaica. The empirical strategy exploits variation arising from the storms’ timing and intensity across different cohorts within the same district. The findings rule out medium-to-large overall adverse effects of tropical storms. However, when expectant mothers living in coastal-rural areas are affected by the cumulative destruction of two hurricanes, their children experience negative impacts on both weight-for-age and weight-for-height measures. PURPOSE To investigate the effects of heart beat rate (bpm), vessel angulation and acquisition protocol on the estimation accuracy of calcified stenosis using a dual-energy CT scanner. METHODS A thorax semi-anthropomorphic phantom coupled with a motion simulator and a vessel phantom representing a 50% coronary artery calcified stenosis, were used. Electrocardiograph (ECG)-synchronized acquisitions were performed at different bpms. buy JNK Inhibitor VIII Acquisitions were performed using A, B, and C single-energy and D dual-energy protocols. Protocol A was prospective ECG-triggered axial and protocols B and C were retrospective single- and two-segment reconstruction ECG-gated helical acquisitions. Protocol D was prospective ECG-triggered axial acquisition. The vessel phantom was placed at two angulations relative to z-axis. Images were reconstructed using all available kernels with iterative reconstruction. Stenosis-percentage was estimated using the CT vendor’s vessel analysis tool. Effective dose (ED) was estimated using the dose-length product method. RESULTS In protocols A, B, and C, measured Stenosis-percentage increased with bpm. Stenosis-percentage estimate ranged from 56.8% at 40 bpm to 62.6% at 100 bpm. In protocol D, Stenosis-percentage ranged from 59.3% at 40 bpm to 54.8% at 80 bpm. Stenosis-percentage was overestimated on respect to the nominal value in most kernels. The detail kernel exhibited the highest accuracy. Stenosis-percentage was not affected by the vessel angulation. ED for protocols A, B, C, and D was 2.4 mSv, 5.1 mSv, 5.5 mSv, and 2.8 mSv, respectively. CONCLUSIONS Use of the dual-energy cardiac CT examination protocol along with the detail kernel is recommended for a more accurate assessment of Stenosis-percentage.