DataSheet_2_Dimethyl fumarate alleviates allergic asthma by strengthening the Nrf2 signaling pathway in regulatory T cells.pdf

Allergic asthma is a widely prevalent inflammatory condition affecting people across the globe. T cells and their secretory cytokines are central to the pathogenesis of allergic asthma. Here, we have evaluated the anti-inflammatory impact of dimethyl fumarate (DMF) in allergic asthma with more focus on determining its effect on T cell responses in allergic asthma. By utilizing the ovalbumin (OVA)-induced allergic asthma model, we observed that DMF administration reduced the allergic asthma symptoms and IgE levels in the OVA-induced mice model. Histopathological analysis showed that DMF treatment in an OVA-induced animal model eased the inflammation in the nasal and bronchial tissues, with a particular decrease in the infiltration of immune cells. Additionally, RT-qPCR analysis exhibited that treatment of DMF in an OVA-induced model reduced the expression of inflammatory cytokine (IL4, IL13, and IL17) while augmenting anti-inflammatory IL10 and Foxp3 (forkhead box protein 3). Mechanistically, we found that DMF increased the expression of Foxp3 by exacerbating the expression of nuclear factor E2-related factor 2 (Nrf2), and the in-vitro activation of Foxp3+ Tregs leads to an escalated expression of Nrf2. Notably, CD4-specific Nrf2 deletion intensified the allergic asthma symptoms and reduced the in-vitro iTreg differentiation. Meanwhile, DMF failed to exert protective effects on OVA-induced allergic asthma in CD4-specific Nrf2 knock-out mice. Overall, our study illustrates that DMF enhances Nrf2 signaling in T cells to assist the differentiation of Tregs, which could improve the anti-inflammatory immune response in allergic asthma.</p

Table_1_Dimethyl fumarate alleviates allergic asthma by strengthening the Nrf2 signaling pathway in regulatory T cells.xlsx

Allergic asthma is a widely prevalent inflammatory condition affecting people across the globe. T cells and their secretory cytokines are central to the pathogenesis of allergic asthma. Here, we have evaluated the anti-inflammatory impact of dimethyl fumarate (DMF) in allergic asthma with more focus on determining its effect on T cell responses in allergic asthma. By utilizing the ovalbumin (OVA)-induced allergic asthma model, we observed that DMF administration reduced the allergic asthma symptoms and IgE levels in the OVA-induced mice model. Histopathological analysis showed that DMF treatment in an OVA-induced animal model eased the inflammation in the nasal and bronchial tissues, with a particular decrease in the infiltration of immune cells. Additionally, RT-qPCR analysis exhibited that treatment of DMF in an OVA-induced model reduced the expression of inflammatory cytokine (IL4, IL13, and IL17) while augmenting anti-inflammatory IL10 and Foxp3 (forkhead box protein 3). Mechanistically, we found that DMF increased the expression of Foxp3 by exacerbating the expression of nuclear factor E2-related factor 2 (Nrf2), and the in-vitro activation of Foxp3+ Tregs leads to an escalated expression of Nrf2. Notably, CD4-specific Nrf2 deletion intensified the allergic asthma symptoms and reduced the in-vitro iTreg differentiation. Meanwhile, DMF failed to exert protective effects on OVA-induced allergic asthma in CD4-specific Nrf2 knock-out mice. Overall, our study illustrates that DMF enhances Nrf2 signaling in T cells to assist the differentiation of Tregs, which could improve the anti-inflammatory immune response in allergic asthma.</p

DataSheet_1_Dimethyl fumarate alleviates allergic asthma by strengthening the Nrf2 signaling pathway in regulatory T cells.docx

Allergic asthma is a widely prevalent inflammatory condition affecting people across the globe. T cells and their secretory cytokines are central to the pathogenesis of allergic asthma. Here, we have evaluated the anti-inflammatory impact of dimethyl fumarate (DMF) in allergic asthma with more focus on determining its effect on T cell responses in allergic asthma. By utilizing the ovalbumin (OVA)-induced allergic asthma model, we observed that DMF administration reduced the allergic asthma symptoms and IgE levels in the OVA-induced mice model. Histopathological analysis showed that DMF treatment in an OVA-induced animal model eased the inflammation in the nasal and bronchial tissues, with a particular decrease in the infiltration of immune cells. Additionally, RT-qPCR analysis exhibited that treatment of DMF in an OVA-induced model reduced the expression of inflammatory cytokine (IL4, IL13, and IL17) while augmenting anti-inflammatory IL10 and Foxp3 (forkhead box protein 3). Mechanistically, we found that DMF increased the expression of Foxp3 by exacerbating the expression of nuclear factor E2-related factor 2 (Nrf2), and the in-vitro activation of Foxp3+ Tregs leads to an escalated expression of Nrf2. Notably, CD4-specific Nrf2 deletion intensified the allergic asthma symptoms and reduced the in-vitro iTreg differentiation. Meanwhile, DMF failed to exert protective effects on OVA-induced allergic asthma in CD4-specific Nrf2 knock-out mice. Overall, our study illustrates that DMF enhances Nrf2 signaling in T cells to assist the differentiation of Tregs, which could improve the anti-inflammatory immune response in allergic asthma.</p

Zwitterionic Nickel(II) Catalyst for CO–Ethylene Alternating Copolymerization

A zwitterionic nickel­(II) catalyst has been discovered to display an initial catalytic activity comparable to that of cationic palladium catalysts for alternating copolymerization of carbon monoxide and ethylene. This demonstrates the absence of a severe dormant state in the present zwitterionic system, in contrast to the cationic nickel­(II) catalysts. However, the highly active catalyst is short-lived. Stoichiometric decomposition of the catalyst under carbon monoxide suggests that the insufficient stability of the tetraphenylborate motif in the ligand framework with respect to electrophilic attack is likely a culprit for catalyst deactivation

Zwitterionic Nickel(II) Catalyst for CO–Ethylene Alternating Copolymerization

A zwitterionic nickel­(II) catalyst has been discovered to display an initial catalytic activity comparable to that of cationic palladium catalysts for alternating copolymerization of carbon monoxide and ethylene. This demonstrates the absence of a severe dormant state in the present zwitterionic system, in contrast to the cationic nickel­(II) catalysts. However, the highly active catalyst is short-lived. Stoichiometric decomposition of the catalyst under carbon monoxide suggests that the insufficient stability of the tetraphenylborate motif in the ligand framework with respect to electrophilic attack is likely a culprit for catalyst deactivation

Zwitterionic Nickel(II) Catalysts for CO–Ethylene Alternating Copolymerization

A new zwitterionic nickel­(II) catalyst that comprises a partially fluorinated tetrakis­(aryl)­borate center in a bidentate phosphine ligand and a cationic Ni center has been developed and studied for CO–ethylene copolymerization in the context of comparison with a previously reported zwitterionic catalyst that carries a nonfluorinated borate anion. The crystal structures of several zwitterionic and related nickel compounds are characterized. Partial fluorination of the tetrakis­(aryl)­borate only brings a modest increase in productivity (2700 vs 1600 g of polyketone per gram of Ni, g (g of Ni)⁻¹). Like the nonfluorinated catalyst, the fluorinated zwitterionic catalyst is extremely active at the beginning of the polymerization but deactivates rapidly. Deactivation of the two catalysts apparently follows different mechanisms. Stoichometric decomposition studies show that the partially fluorinated tetrakis­(aryl)­borate in the Ni compounds is stable under acidic conditions either directly introduced by addition of an acid or created by a CO atmosphere. In contrast, the nonfluorinated tetrakis­(aryl)­borate is readily decomposed by an acid or under acidic conditions created by CO. For the new catalyst system with the partially fluorinated tetrakis­(aryl)­borate anion, the deactivation likely involves initially redox processes and eventually ligand redistribution around Ni, as inferred from the stoichiometric decomposition studies. It turns out that such a process allows the deactivated catalyst to be reactivated by H₂. When the polymerization is carried out in the presence of H₂, the productivity of the new zwitterionic catalyst can reach 6400 g (g of Ni)⁻¹. The zwitterionic catalyst with the nonfluorinated tetrakis­(aryl)­borate anion cannot be reactivated by H₂. A cationic analogue of the zwitterionic catalysts is also studied for comparison. Its productivity for CO–ethylene copolymerization (230 g (g of Ni)⁻¹) is about 1 order of magnitude lower than that of the zwitterionic catalysts, demonstrating the critical role of the zwitterionic character in attaining the aforementioned high productivity. At the productivity level of the zwitterionic catalysts, which to our knowledge is among the highest observed for Ni catalysts, an unacceptable amount of residual Ni­(II) species is left in the product, causing the alternating CO–ethylene copolymer to begin to decompose near its melting temperature and hence making melt processing difficult

Protein expression level of NFκB p65 and c-Jun proteins in the liver after PH.

<p>(A) Lanes 1–3 represent the protein expression level in the control group at 7, 3 and 1 days after PH, respectively. Lanes 4–6 represent the protein expression level in NCPB group at 1, 3 and 7 days after PH, respectively. The expression of NF-κB p65 and c-Jun were detected by Western blot analysis and normalized to response to β-actin. (B–C) represent the statistical charts of NF-κB p65 and c-Jun proteins expressions in the liver after PH, respectively, and asterisks indicate significant differences from control group. *p<0.05; **p<0.01.</p

Hepatic blood flow and liver function after PH. Rats were divided into 2 groups (n = 10).

<p>The rats were observed at 1, 3, and 7 days after PH. Asterisks indicate significant difference from control group, *p<0.05; **p<0.01.</p

Protein expression level of VEGF, Bax and Bcl-2 proteins in the liver after PH.

<p>(A) Lanes 1–3 represent the protein expression level in the control group at 7, 3 and 1 days after PH, respectively. Lanes 4–6 represent the protein expression level in NCPB group at 1, 3 and 7 days after PH, respectively. The expression of VEGF, Bax, and Bcl-2 were detected by Western blot analysis and normalized to response to β-actin. (B–D) represent the statistical charts of VEGF, Bax, and Bcl-2 expressions in the liver after PH, respectively, and asterisks indicate significant differences from control group. *p<0.05; **p<0.01.</p

Expressions of VEGF in the liver tissues. (×40).

<p>Expressions of VEGF in the liver tissues. (×40).</p