Objective： To evaluate the regulatory effects of Banxia （Pinellia ternata, P） and Huanglian （Coptis chinensis, C） drugpair, derived from Banxiaxiexin soup, on the gastrointestinal movement of mice with functional...Objective： To evaluate the regulatory effects of Banxia （Pinellia ternata, P） and Huanglian （Coptis chinensis, C） drugpair, derived from Banxiaxiexin soup, on the gastrointestinal movement of mice with functional dyspepsia. Methods：Mice were treated with different proportions of the P and C drug pair （1：1, 3：1, and 4：1） for 10 days, and subsequentlyinjected with atropine （ATR） or neostigmine （NEO）. The effects of the different proportions of P and C were evaluatedbased on the alvine advance rate. In addition, we used the same modeling method used in the first experiment andadministered P： C at ratio of 3：1 and at different doses respectively （4.68 g/L, 2.34 g/L, and 1.17 g/L）, and tested levelsof the gastrointestinal hormones, gastrin （GAS）, vasoactive intestinal polypeptide （VIP）, and somatostatin （SS） in thesmall intestinal tissue using an enzyme-linked immunosorbent assay. Results： In the groups of NEO-induced mice, P：Cat ratios of 1：1, 3：1, and 4：1 significantly reduced the alvine advance rate compared with the NEO model group （P =0.003, P = 0.012 and P = 0.021, respectively）. In the groups of ATR-induced mice, only P：1 at ratio of 3：1 significantlyincreased the alvine advance rate compared with the ATR model group （P = 0.007）. After exposure to P： C at ratio of 3：1and at different dose, the GAS level was lower in the low-, medium-, and high-dose NEO groups than that in the NEOmodel group （P = 0.001, P = 0.004, and P = 0.003, respectively）. The VIP levels were higher in the medium-andhigh-dose NEO groups than that in the NEO model group （P = 0.004 and P = 0.002, respectively）. In addition, the SSlevel increased in the NEO medium-dose group compared with that in the NEO model group （P = 0.002）. The GAS levelwas higher in the ATR medium- and high-dose groups than in the ATR model group （P = 0.007 and P = 0.021,respectively）. The VIP level was lower in the ATR low-, medium-, and high-dose than that in the ATR model group （P =0.001, P = 0.001, and P = 0.001, respectively）. Furthermore, the SS level was lower in the ATR medium- and high-dosegroups than that in the ATR model group （P = 0.001 and P = 0.006）. Conclusion： The PC drug pair bidirectionallyadjusted the NEO- and ATR-induced functional dyspepsia in mice by modulating GAS, VIP, and SS levels in theintestine.展开更多
Acute viral infection causes illness and death.In addition,an infection often results in increased susceptibility to a secondary infection,but the mechanisms behind this susceptibility are poorly understood.Since its ...Acute viral infection causes illness and death.In addition,an infection often results in increased susceptibility to a secondary infection,but the mechanisms behind this susceptibility are poorly understood.Since its initial identification as a marker for resident memory CD8^(+)T cells in barrier tissues,the function and regulation of CD103 integrin(encoded by ITGAE gene)have been extensively investigated.Nonetheless,the function and regulation of the resident CD103^(+)CD8^(+)T cell response to acute viral infection remain unclear.Although TGFβsignaling is essential for CD103 expression,the precise molecular mechanism behind this regulation is elusive.Here,we reveal a TGFβ–SKI–Smad4 pathway that critically and specifically directs resident CD103^(+)CD8^(+)T cell generation for protective immunity against primary and secondary viral infection.We found that resident CD103^(+)CD8^(+)T cells are abundant in both lymphoid and nonlymphoid tissues from uninfected mice.CD103 acts as a costimulation signal to produce an optimal antigenic CD8^(+)T cell response to acute viral infection.There is a reduction in resident CD103^(+)CD8^(+)T cells following primary infection that results in increased susceptibility of the host to secondary infection.Intriguingly,CD103 expression inversely and specifically correlates with SKI proto-oncogene(SKI)expression but not R-Smad2/3 activation.Ectopic expression of SKI restricts CD103 expression in CD8^(+)T cells in vitro and in vivo to hamper viral clearance.Mechanistically,SKI is recruited to the Itgae loci to directly suppress CD103 transcription by regulating histone acetylation in a Smad4-dependent manner.Our study therefore reveals that resident CD103^(+)CD8^(+)T cells dictate protective immunity during primary and secondary infection.Interfering with SKI function may amplify the resident CD103^(+)CD8^(+)T cell response to promote protective immunity.展开更多
文摘Objective： To evaluate the regulatory effects of Banxia （Pinellia ternata, P） and Huanglian （Coptis chinensis, C） drugpair, derived from Banxiaxiexin soup, on the gastrointestinal movement of mice with functional dyspepsia. Methods：Mice were treated with different proportions of the P and C drug pair （1：1, 3：1, and 4：1） for 10 days, and subsequentlyinjected with atropine （ATR） or neostigmine （NEO）. The effects of the different proportions of P and C were evaluatedbased on the alvine advance rate. In addition, we used the same modeling method used in the first experiment andadministered P： C at ratio of 3：1 and at different doses respectively （4.68 g/L, 2.34 g/L, and 1.17 g/L）, and tested levelsof the gastrointestinal hormones, gastrin （GAS）, vasoactive intestinal polypeptide （VIP）, and somatostatin （SS） in thesmall intestinal tissue using an enzyme-linked immunosorbent assay. Results： In the groups of NEO-induced mice, P：Cat ratios of 1：1, 3：1, and 4：1 significantly reduced the alvine advance rate compared with the NEO model group （P =0.003, P = 0.012 and P = 0.021, respectively）. In the groups of ATR-induced mice, only P：1 at ratio of 3：1 significantlyincreased the alvine advance rate compared with the ATR model group （P = 0.007）. After exposure to P： C at ratio of 3：1and at different dose, the GAS level was lower in the low-, medium-, and high-dose NEO groups than that in the NEOmodel group （P = 0.001, P = 0.004, and P = 0.003, respectively）. The VIP levels were higher in the medium-andhigh-dose NEO groups than that in the NEO model group （P = 0.004 and P = 0.002, respectively）. In addition, the SSlevel increased in the NEO medium-dose group compared with that in the NEO model group （P = 0.002）. The GAS levelwas higher in the ATR medium- and high-dose groups than in the ATR model group （P = 0.007 and P = 0.021,respectively）. The VIP level was lower in the ATR low-, medium-, and high-dose than that in the ATR model group （P =0.001, P = 0.001, and P = 0.001, respectively）. Furthermore, the SS level was lower in the ATR medium- and high-dosegroups than that in the ATR model group （P = 0.001 and P = 0.006）. Conclusion： The PC drug pair bidirectionallyadjusted the NEO- and ATR-induced functional dyspepsia in mice by modulating GAS, VIP, and SS levels in theintestine.
基金This work was supported by NIH funding(R01Al143894,R01Al138337)for J.K.W.the NIH(Al123193)+1 种基金the National Multiple Sclerosis Society(RG-1802-30483)the Yang Family Biomedical Scholars Award for Y.Y.W.
文摘Acute viral infection causes illness and death.In addition,an infection often results in increased susceptibility to a secondary infection,but the mechanisms behind this susceptibility are poorly understood.Since its initial identification as a marker for resident memory CD8^(+)T cells in barrier tissues,the function and regulation of CD103 integrin(encoded by ITGAE gene)have been extensively investigated.Nonetheless,the function and regulation of the resident CD103^(+)CD8^(+)T cell response to acute viral infection remain unclear.Although TGFβsignaling is essential for CD103 expression,the precise molecular mechanism behind this regulation is elusive.Here,we reveal a TGFβ–SKI–Smad4 pathway that critically and specifically directs resident CD103^(+)CD8^(+)T cell generation for protective immunity against primary and secondary viral infection.We found that resident CD103^(+)CD8^(+)T cells are abundant in both lymphoid and nonlymphoid tissues from uninfected mice.CD103 acts as a costimulation signal to produce an optimal antigenic CD8^(+)T cell response to acute viral infection.There is a reduction in resident CD103^(+)CD8^(+)T cells following primary infection that results in increased susceptibility of the host to secondary infection.Intriguingly,CD103 expression inversely and specifically correlates with SKI proto-oncogene(SKI)expression but not R-Smad2/3 activation.Ectopic expression of SKI restricts CD103 expression in CD8^(+)T cells in vitro and in vivo to hamper viral clearance.Mechanistically,SKI is recruited to the Itgae loci to directly suppress CD103 transcription by regulating histone acetylation in a Smad4-dependent manner.Our study therefore reveals that resident CD103^(+)CD8^(+)T cells dictate protective immunity during primary and secondary infection.Interfering with SKI function may amplify the resident CD103^(+)CD8^(+)T cell response to promote protective immunity.
