Palladium/Silver-Cocatalyzed Tandem Reactions of Oxabenzonorbornadienes with Substituted Arylacetylenes: A Simple Method for the Preparation of 1,2-Diarylethanones and 1,2-Diarylacetylenes

The effective synthesis of 1,2-diarylethanones was achieved using palladium­(II) acetate [Pd­(OAc)₂] and silver triflate (AgOTf) as cocatalysts from various oxabenzonorbornadiene derivatives and substituted arylacetylenes via tandem reactions under mild conditions. Exploration of the oxabenzonorbornadiene substrates showed that the 1,2-diarylacetylenes were obtained from adjacent alkoxy substituted oxabenzonorbornadiene derivatives. Preliminary mechanistic studies indicate that the AgOTf served as an indispensable catalyst, and the mechanism of the tandem reaction was proposed

Presentation_1_The p38 MAPK Inhibitor SB203580 Abrogates Tumor Necrosis Factor-Induced Proliferative Expansion of Mouse CD4+Foxp3+ Regulatory T Cells.pdf

<p>There is now compelling evidence that tumor necrosis factor (TNF) preferentially activates and expands CD4⁺Foxp3⁺ regulatory T cells (Tregs) through TNF receptor type II (TNFR2). However, it remains unclear which signaling transduction pathway(s) of TNFR2 is required for the stimulation of Tregs. Previously, it was shown that the interaction of TNF–TNFR2 resulted in the activation of a number of signaling pathways, including p38 MAPK, NF-κB, in T cells. We thus examined the role of p38 MAPK and NF-κB in TNF-mediated activation of Tregs, by using specific small molecule inhibitors. The results show that treatment with specific p38 MAPK inhibitor SB203580, rather than NF-κB inhibitors (Sulfasalazine and Bay 11-7082), abrogated TNF-induced expansion of Tregs in vitro. Furthermore, upregulation of TNFR2 and Foxp3 expression in Tregs by TNF was also markedly inhibited by SB203580. The proliferative expansion and the upregulation of TNFR2 expression on Tregs in LPS-treated mice were mediated by TNF–TNFR2 interaction, as shown by our previous study. The expansion of Tregs in LPS-treated mice were also markedly inhibited by in vivo treatment with SB203580. Taken together, our data clearly indicate that the activation of p38 MAPK is attributable to TNF/TNFR2-mediated activation and proliferative expansion of Tregs. Our results also suggest that targeting of p38 MAPK by pharmacological agent may represent a novel strategy to up- or downregulation of Treg activity for therapeutic purposes.</p

The Shared Crosstalk of Multiple Pathways Involved in the Inflammation between Rheumatoid Arthritis and Coronary Artery Disease Based on a Digital Gene Expression Profile

<div><p>Rheumatoid arthritis (RA) and coronary artery disease (CAD) are both complex inflammatory diseases, and an increased prevalence of CAD and a high rate of mortality have been observed in RA patients. But the molecular mechanism of inflammation that is shared between the two disorders is unclear. High-throughput techniques, such as transcriptome analysis, are becoming important tools for genetic biomarker discovery in highly complex biological samples, which is critical for the diagnosis, prognosis, and treatment of disease. In the present study, we reported one type of transcriptome analysis method: digital gene expression profiling of peripheral blood mononuclear cells of 10 RA patients, 10 CAD patients and 10 healthy people. In all, 213 and 152 differently expressed genes (DEGs) were identified in RA patients compared with normal controls (RA <i>vs.</i> normal) and CAD patients compared with normal controls (CAD <i>vs.</i> normal), respectively, with 73 shared DEGs between them. Using this technique in combination with Ingenuity Pathways Analysis software, the effects on inflammation of four shared canonical pathways, three shared activated predicted upstream regulators and three shared molecular interaction networks were identified and explored. These shared molecular mechanisms may provide the genetic basis and potential targets for optimizing the application of current drugs to more effectively treat these diseases simultaneously and for preventing one when the other is diagnosed.</p></div

Network, molecular functions and canonical pathway analysis of shared DEGs in RA <i>vs.</i> normal and CAD <i>vs</i>. normal individuals.

<p>A: The molecular network of 95 shared DEGs in RA <i>vs.</i> normal and CAD <i>vs.</i> normal individuals; blue molecules represent the shared DEGs; B: the top 4 shared canonical pathways (with score (-log (<i>p</i>-value))>1.3, <i>p</i>-value of pathway <0.05) related with inflammation which 95 shared DEGs in RA vs. normal and CAD vs. normal involved in: IL-8 signaling; antigen presentation pathway; OX40 signaling pathway; TREM1 signaling; C: the function classification of shared DEGs in both RA <i>vs.</i> normal and CAD <i>vs.</i> normal, the number in the bar diagram represented the DEGs numbers participated in the corresponding pathways.</p

The top 4 shared signaling pathways related to inflammation and shared DEGs in both RA <i>vs</i>. normal and CAD <i>vs</i>. normal subjects.

<p>The top 4 shared signaling pathways related to inflammation and shared DEGs in both RA <i>vs</i>. normal and CAD <i>vs</i>. normal subjects.</p

The shared molecular networks and upstream regulators networks of RA and CAD.

<p>A: shared associated network (SAN) -1; B: SAN-2; C: SAN-3; D: the network of upstream regulators and target molecules of DEGs in RA; E: the network of upstream regulators and target molecules of DEGs in CAD; F: the legends of predicted networks. In A, B and C, the molecules with orange circles stand for shared molecules between RA and CAD.</p

The significant commonly shared signaling canonical pathways between RA and CAD involved in inflammation.

<p>A: IL-8 signaling; B: antigen presentation pathway; C: OX40 signaling pathway; D: TREM1 signaling; E: picture legends. Purple circle: the same genes involved in the commonly shared pathways in RA and CAD.</p

Baseline characteristics of the RA, CAD patients and normal groups.

<p>Baseline characteristics of the RA, CAD patients and normal groups.</p

The Crosstalk of Pathways Involved in Immune Response Maybe the Shared Molecular Basis of Rheumatoid Arthritis and Type 2 Diabetes

<div><p>Rheumatoid arthritis (RA) and Type 2 diabetes (T2D) are both systemic diseases linked with altered immune response, moderate mortality when present together. The treatment for both RA and T2D are not satisfied, partly because of the linkage between them has not yet been appreciated. A comprehensive study for the potential associations between the two disorders is needed. In this study, we used RNA sequencing to explore the differently expressed genes (DEGs) in peripheral blood mononuclear cells (PBMC) of 10 RA and 10 T2D patients comparing with 10 healthy volunteers (control). We used bioinformatics analysis and the Ingenuity Pathways Analysis (IPA) to predict the commonalities on signaling pathways and molecular networks between those two diseases. 212 DEGs in RA and 114 DEGs in T2D patients were identified compared with healthy controls, respectively. 32 DEGs were shared between the two comparisons. The top 10 shared pathways interacted in cross-talking networks, regulated by 5 shared predicted upstream regulators, leading to the activated immune response were explored, which was considered as partly of the association mechanism of this two disorders. These discoveries would be considered as new understanding on the associations between RA and T2D, and provide novel treatment or prevention strategy.</p></div

The top functions of predicted upstream regulators networks in RA <i>vs</i>. normal and CAD <i>vs</i>. normal and targets molecules involved in (The molecules in italics are shared predicted upstream regulators and targets in both RA <i>vs.</i> normal and CAD <i>vs.</i> normal groups).

<p>The top functions of predicted upstream regulators networks in RA <i>vs</i>. normal and CAD <i>vs</i>. normal and targets molecules involved in (The molecules in italics are shared predicted upstream regulators and targets in both RA <i>vs.</i> normal and CAD <i>vs.</i> normal groups).</p