Allergic inflammation is exacerbated by allergen-induced type 2 innate lymphoid cells in a murine model of allergic rhinitis.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) represent a new innate effector leukocyte population that mediates type-2 immune response. However, the contribution of ILC2s to allergic rhinitis (AR) is currently not well defined. OBJECTIVE: To evaluate the potential existence and function of allergen-induced ILC2s in the experimental AR. METHODS: We established a murine model of AR using ovalbumin (OVA) and aluminium hydroxide. The OVA-induced ILC2s were sorted and purified from the mouse nasal-associated lymphoid tissue (NALT). Then, we assessed ILC2s responses to mouse recombinant interleukin (rmIL)-25, anti-IL17RB antibody and CC chemokine ligand (CCL) 25 in the culture. After that, we adoptively transferred the NALT-derived ILC2s alone or plus rmIL-25 or anti-IL17RB antibody to the murine model of AR to investigate their role in the nasal allergic inflammation. RESULTS: We showed that ILC2s could be induced by OVA in the NALT of AR model. They were induced to secrete IL-5 and IL-13 by rmIL-25, and blocking of IL17RB contributed to the decreased production of these cytokines in the culture. We found that CCL25 induced the NALT-derived ILC2s migration through CC chemokine receptor 9 on ILC2s in vitro. Numbers of sneezing and nasal rubbing as well as counts of invasive eosinophils were all enhanced after the adoptive transfer of cultured ILC2s in vitro. The expressions of IL-5, IL-13, IL-25 and CCL25 in the NLF of allergic mice were also increased. CONCLUSION: These findings show that ILC2s play a proinflammatory role in the murine AR model, and also highlight ILC2s as a new target in the future AR therapy.

[Preventing and treating anterior commissure adhesion with mucosal flap: a study in canines and clinical cases].

Objective: To evaluate the effectiveness of mucosal flap combined with silicone keel for preventing and treating anterior commissure adhesion in canines and clinical cases. Methods: A prospective experiment was performed from November 2019 to June 2021. Twenty five canines were randomly divided into 5 groups(A, B, C, D, E). Group A, B, C, D received anterior commissure injury by CO2 laser, then separately treated with free mucosal flap-keel complex,intralaryngeal mucosal flap-keel complex, silicone keels and without treatment, group E didn't injure the vocal cord after intubation. The keel was removed after 2 weeks, the larynx was harvested after 4 weeks. The effectiveness of anterior commissure adhesion prevention was evaluated by manifestation under laryngoscope, standard vocal cord length and standard glottic area. A retrospective analysis was performed on sixteen patients with anterior commissure lesion, who underwent mucosal flap-keel technique in Huashan Hospital of Fudan University from January 2019 to January 2021 (10 cases with free mucosal flap-keel complex and 6 cases with intralaryngeal mucosal flap-keel complex). All the patients underwent evaluation of laryngeal function included manifestation under laryngoscope each month and voice analysis before and 3 month after surgery. SPSS 20.0 software was used for statistical analysis. Results: No surgery accident or complication happened in canines and patients. The standard vocal cord length and standard glottic area after 4 weeks in group B were significantly higher than those in group A, C, D (Hstandard vocal cord length=31.688, Hstandard glottic area=16.444, P<0.05). The standard vocal cord length and standard glottic area after 4 weeks in group A were also significantly higher than those in group C, D(Hstandard vocal cord length=20.936, Hstandard glottic area=11.786, P<0.05). The standard vocal cord length and standard glottic area after 4 weeks in group A, B, E were not significantly different to that before surgery(tA left standard vocal cord length=2.636, tA right standard vocal cord length=2.582, tB left standard vocal cord length=2.707, tB right standard vocal cord length=2.673, tE left standard vocal cord length=0.370, tE right standard vocal cord length=0.821, tA standard glottic area=2.731, tB standard glottic area=2.753, tE standard glottic area=-0.529, P>0.05). The standard vocal cord length and standard glottic area after 4 weeks in group C, D were significantly lower than those before surgery(tC left standard vocal cord length=16.137, tC right standard vocal cord length=13.984, tD left standard vocal cord length=11.903, tD right standard vocal cord length=14.587, tC standard glottic area=10.280, tD standard glottic area=22.974, P<0.05). During 6-18 months of follow-up in clinical patients, no one developed a glottic web. Three months after surgery, Jitter, Shimmer, noise to harmonic ratio(NHR), the maximum phonation time(MPT)in all patients were significantly different from preoperative(tintralaryngeal mucosal flap jitter=24.885, tintralaryngeal mucosal flap shimmer=22.643, tintralaryngeal mucosal flap NHR=6.202, tintralaryngeal mucosal flap MPT=-9.661, tfree mucosal flap jitter=25.459, tfree mucosal flap shimmer=18.683, tfree mucosal flap NHR=5.705, tfree mucosal flap MPT=-20.840, P<0.05). Conclusion: Mucosal flap combined with silicone keel is an effective technique for preventing and treating anterior commissure adhesion. The effect of pedicled intralaryngea lmucosal flap is better.

Naringin protects against anoxia/reoxygenation-induced apoptosis in H9c2 cells via the Nrf2 signaling pathway.

Naringin (Nar) is a major and active flavanone glycoside derivative of several citrus species. The antioxidant properties of Nar have an important function in its cardioprotective effects in various models. However, the effects of Nar on Nrf2 activation and the expression of its downstream genes in myocardial cells are yet to be elucidated. This study was designed to investigate the protective effects of Nar against anoxia/reoxygenation (A/R)-induced injury in H9c2 cells and determine its effects on the activity of Nrf2 and the expression of phase II antioxidant enzymes. H9c2 cells were pretreated with Nar for 6 h before exposure to A/R. A/R treatment severely injured the H9c2 cells, which was accompanied by apoptosis. Nar also suppressed the A/R-induced mitochondrial membrane depolarization and caspase-3 activation. Nar pretreatment significantly reduced the apoptotic rate by enhancing the endogenous anti-oxidative activity of superoxide dismutase, glutathione peroxidase, and catalase, thereby inhibiting intracellular reactive oxygen species generation. Moreover, the presence of Nar alone in H9c2 cells increased the nuclear translocation of Nrf2 in a dose- and time-dependent manner, as well as consistently increased the protein levels of heme oxygenase (HO-1) and glutamate cysteine ligase (GCLC). Nar increased the phosphorylation of ERK1/2, PKCδ, and AKT. However, the Nar-mediated Nrf2 activation and cardioprotection were abolished through the genetic silencing of Nrf2 by siRNA and partially inhibited by specific inhibitors of ERK1/2, PKCδ, and AKT. Therefore, Nar provided cardioprotection by inducing the phosphorylation of ERK1/2, PKCδ, and AKT, which subsequently activated Nrf2 and its downstream genes.