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Bronchial asthma is a chronic inflammatory disease of the airways involving a variety of inflammatory cells and cellular components. To study the pathogenesis, treatment, and prognosis of this disease, a reliable animal model must be established. This article summarizes and evaluates the modeling methods for asthmatic animals and presents comprehensive comparison of the study of bronchial asthma animal models from different perspectives, hoping to provide a reference for researchers in the future.

We performed a systematic study of the vibrationally resolved absorption spectra in the Q band of three metalloporphyrins (Mg, Zn, and Pd) to understand the spectral changes in this series, including both the Franck-Condon (FC) and Herzberg-Teller (HT) contributions. The ground (S0) and the lowest singlet excited (S1) states were, respectively, simulated by the static and time-dependent density functional theory, with which the Duschinsky rotation effect was considered. Different functionals and basis sets were tested and compared with experiment. Results show that the long-range corrected functional CAM-B3LYP can nicely describe the spectral fingerprints of these metalloporphyrins, while the B3LYP functional significantly underestimates the FC contributions. We found that the absorption fine structures of these molecules are mainly caused by the HT vibronic couplings. The experimentally observed enhancements to the on-site 0-0 absorption peak in the series of Mg, Zn, and Pd are nicely reproduced. Enhanced absorption intensity is caused by larger FC contributions of molecules with heavier metal ions. The structure-spectroscopy relationship was analyzed, and it was found that the smaller cavity size of the porphyrin ring can significantly enhance the oscillator strength of the S0 → S1 transition. [ABSTRACT FROM AUTHOR]

The vibrationally resolved fluorescence spectrum of a narrow-line single-molecule transducer, fused 5,15-(diphenyl)-10,20-(dibromo)porphyrin (fused-H2P) molecule, has been calculated by time-dependent density functional theory with the inclusion of both Franck-Condon and Herzberg-Teller contributions. Analytical transition dipole derivatives are used for the calculations of Herzberg-Teller terms to eliminate the possible errors caused by numerical differentials. The performance of different exchange-correlation functionals including B3LYP, ωB97X-D, and M06-2X has been examined. The comparison with the high-resolution experimental emission spectrum indicates that all three functionals can satisfactorily describe the fluorescence spectral profile, while ωB97X-D and M06-2X give slightly better excitation energy than B3LYP. Detailed analysis shows that the fluorescence spectrum is dominated by the Franck-Condon contribution, while the Herzberg-Teller term contributes mostly to its low energy tail. It is found that the size of the basis set has limited influence on the fluorescence spectrum, and a standard 6-31G(d, p) basis set is adequate for the purpose. The substitution of terthiophene side chains is found to have minor effects on the fluorescence spectrum. Our study provides unambitious assignments for all the vibronic structures in the experimental spectrum. [ABSTRACT FROM AUTHOR]

Emerging evidence has linked the gut microbiota dysbiosis to transplant rejection while memory T-cells pose a threat to long-term transplant survival. However, it's unclear if the gut microbiome alters the formation and function of alloreactive memory T-cells. Here we studied the effects of berberine, a narrow-spectrum antibiotic that is barely absorbed when orally administered, on the gut microbiota, memory T-cells, and allograft survival. In this study, C57BL/6 mice transplanted with islets or a heart from BALB/c mice were treated orally with berberine. Allograft survival was observed, while spleen, and lymph node T-cells from recipient mice were analyzed using a flow cytometer. High-throughput sequencing and qPCR were performed to analyze the gut microbiota. CD8+ T-cells from recipients were cultured with the bacteria to determine potential T-cell memory cross-reactivity to a specific pathogen. We found that berberine suppressed islet allograft rejection, reduced effector CD8+CD44highCD62Llow and central memory CD8+CD44highCD62Lhigh T-cells (TCM), altered the gut microbiota composition and specifically lowered Bacillus cereus abundance. Further, berberine promoted long-term islet allograft survival induced by conventional costimulatory blockade and induced cardiac allograft tolerance as well. Re-colonization of B. cereus upregulated CD8+ TCM cells and reversed long-term islet allograft survival induced by berberine plus the conventional costimulatory blockade. Finally, alloantigen-experienced memory CD8+ T-cells from transplanted recipients rapidly responded to B. cereus in vitro. Thus, berberine prolonged allograft survival by repressing CD8+ TCM through regulating the gut microbiota. We have provided the first evidence that donor-specific memory T-cell generation is linked to a specific microbe and uncovered a novel mechanism underlying the therapeutic effects of berberine. This study may be implicated for suppressing human transplant rejection since berberine is already used in clinic to treat intestinal infections. [ABSTRACT FROM AUTHOR]

CD4+Foxp3+ regulatory T cells (Tregs) in the tumor microenvironment restrain antitumor immunity, resulting in tumor aggression and poor survival in hepatocellular carcinoma (HCC). CD8+CD122+ Tregs have been previously shown to be more potent in immunosuppression than are CD4+Foxp3+ Tregs. Previous studies have demonstrated that resveratrol exerts its anti-cancer effects by downregulating CD4+Foxp3+ and M2-like macrophages, two key immunoregulatory cells that maintain the immunosuppressive tumor microenvironment. In this study, we found that resveratrol inhibited the tumor growth in a subcutaneous Hepa1-6 HCC model and decreased the frequency of CD8+CD122+ Tregs in the tumor as well as lymph nodes and spleen of the tumor-bearing mice. It also increased the percentage of IFN-γ-expressing CD8+ T cells in the tumor and peripheral lymphoid organs. The antitumor effects of resveratrol were partially reversed by the adoptive transfer of exogenous CD8+CD122+ Tregs into the tumor-bearing mice. Meanwhile, resveratrol treatment downregulated immunosuppressive cytokines, including TGF-β1 and interleukin-10, in the tumor while elevating antitumor cytokines, TNF-α and IFN-γ. It also inhibited the activation of STAT3 signaling in the tumor. As expected, resveratrol reduced the percentage of M2-like macrophages in the mice. Importantly, resveratrol suppressed orthotopic H22 tumor growth and decreased the frequency of CD8+CD122+ Tregs and M2-like macrophages in the tumor-bearing mice. Furthermore, our studies showed that resveratrol, at non-cytotoxic concentrations, inhibited CD8+CD122+ Treg differentiation from CD8+CD122− T cells in vitro. Thus, our studies unveiled a new immune mechanism underlying the immunosuppressive tumor microenvironment and demonstrated that resveratrol could help reverse it by diminishing CD8+CD122+ Tregs. [ABSTRACT FROM AUTHOR]