It Takes Two to Tangle: Microneedle Patches Co-delivering Monoclonal Antibodies and Engineered Antimicrobial Peptides Effectively Eradicate Wound Biofilms.

Wound biofilms pose a great clinical challenge. Herein, this work reports a dissolvable microneedle patch for dual delivery of monoclonal antibodies anti-PBP2a and engineers antimicrobial peptides W379. In vitro antibacterial efficacy testing with microneedle patches containing a combination of 250 ng mL-1 W379 and 250 ng mL-1 anti-BPB2a decreases the bacterial count from ≈3.31 × 107 CFU mL-1 to 1.28 × 102 CFU mL-1 within 2 h without eliciting evident cytotoxicity. Ex vivo testing indicates W379 and anti-PBP2a co-loaded microneedle patch displayed a remarkable reduction of bacterial load by ≈7.18 log CFU after administered only once within 48 h. The bacterial count is significantly diminished compared to the treatment by either W379 or anti-PBP2a-loaded alone microneedle patches. When administered twice within 48 h, no bacteria are identified. Further in vivo study also reveals that after two treatments of W379 and anti-PBP2a co-loaded PVP microneedle patches within 48 h, the bacterial colonies are undetectable in a type II diabetic mouse wound biofilm model. Taken together, W379 and anti-PBP2a co-loaded PVP microneedle patches hold great promise in treating wound biofilms.

Vitamin A deficiency exacerbates extrinsic atopic dermatitis development by potentiating type 2 helper T cell-type inflammation and mast cell activation.

BACKGROUND: Vitamin A deficiency (VAD) has been hypothesized to play a role in the pathophysiology of atopic dermatitis (AD). OBJECTIVE: We sought to verify whether VAD can exacerbate AD development, and explore the possible pathophysiologic mechanism. METHODS: We detected serum vitamin A (VA) concentration in different phenotypes of AD infants (intrinsic AD, iAD and extrinsic AD, eAD), and established ovalbumin (OVA) percutaneous sensitized AD model and passive cutaneous anaphylaxis (PCA) model on VAD and vitamin A supplementation (VAS) model in wild-type mice (C57BL/6) and established AD model on both normal VA (VAN) and VAD feeding mast cell deficiency mice (ckitw-sh/w-sh ). RESULTS: The average serum VA concentration of eAD was significantly lower than that of iAD, as well as healthy controls. In OVA-induced C57BL/6 mouse AD model, compared with VAN group, VAD mice manifested significantly more mast cells accumulation in the skin lesions, more severe Th2-mediated inflammation, including higher serum IgG1 and IgE levels, more IL-4, IL-13 mRNA expression in OVA-sensitized skin, and lower Th1 immune response, including lower serum IgG2a and IFN-γ mRNA expression in the skin. But there was no significant difference in the expression of IL-17 mRNA between OVA-treated skin of VAN and VAD mice. However, in OVA-induced ckitw-sh/w-sh mouse AD model, we did not find any significant differences in the above measurements between VAD and VAN group. In PCA model, VAD mice showed remarkable more blue dye leakage than that in VAN mice. Compared with VAD group, the above-mentioned inflammatory measurements in VAS group and VAN group were similar in OVA-induced AD model mice. CONCLUSIONS AND CLINICAL RELEVANCE: VAD can exacerbate extrinsic AD by augmenting Th2-mediated inflammation and mast cell activation. Therapeutic VAS can rescue VAD-aggravated eAD. It may provide a new strategy for future prevention or treatment of atopic dermatitis.

Low-concentration topical tacrolimus for the treatment of anogenital lichen sclerosus in childhood: maintenance treatment to reduce recurrence.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory skin disorder that is commonly found in the anogenital area, especially in females. Ultra-potent topical corticosteroids are first line for the treatment of LS, but their atrophic side effects and the recurrence of the disease restrict their use. An equally effective, safer, tolerant therapeutic option is required, especially in the treatment and preventing relapse of children. METHODS: Fourteen prepubertal girls (range of age: 4 to 11 years) with anogenital lichen sclerosus were treated with 0.03% tacrolimus ointment twice daily for 16 weeks, then 9 of the 14 patients adhered to 2 times weekly for further 6 months (a total of 10 months). The therapeutic effects were evaluated according to 3 grades: complete response (O75% improvement, partial response (30%-75% improvement),or no response (!30% improvement). RESULTS: Clinical improvement occurred in all patients (100%). Complete response of symptoms and signs was achieved in 5 (36%), 9 (64%) and 11 (79%) patients at week 8, week 16, and month 10 respectively. During the follow-up period of 1 year, 4 patients (4/5, 80%) who treated with tacrolimus ointment for 16 weeks had a recurrence of symptoms, while only 2 of 9 (22%) patients who insisted on maintenance therapy developed recurrence of disease. No severe side effects were observed. CONCLUSIONS: Low-concentration topical tacrolimus appears to be an effective and safe treatment for children with anogenital lichen sclerosus. Maintenance therapy (2 times a week for 6 months) can reduce the relapse of the disease.

Correlation between interleukin-31 expression on peripheral blood mononuclear cells and disease severity of pediatric patients with atopic dermatitis / 中华皮肤科杂志

Objective To evaluate the significance of human interleukin-31(IL-31)in the pathogenesis of atopic dermatitis and its correlation with pruritus in patients with atopic dermatitis(AD).Methods Twenty-two children with mild to severe atopic dermatitis and 22 age-matched healthy controls were included in this study.Patients and controls were randomly and equally assigned into stimulation and non-stimulation groups.Venous blood samples were obtained from all participants,peripheral blood mononuclear cells were isolated from these samples and cultured with(stimulation groups)or without(non-stimulation groups)staphylococcal enterotoxin B(SEB)for 24 hours.Then,the mRNA expression of IL-31 on PBMCs was assessed via real-time reverse transcription-PCR.ELISA was used to detect the total serum IgE level in these objects.The severity of AD in patients was rated according to scoring atopic dermatitis(SCORAD).The relationship between the mRNA expression of IL-31 and the level of serum total IgE.severity of atopic dermatitis,and degree of pruritus.was evaluated.Results The expression of IL-31 mRNA on non-stimulated PBMCs from patients was 23.2 folds as high as that from the healthy controls(P＜0.01).The stimulation with SEB upregulated the mRNA expression of IL-31 on PBMCs.and the increase on PBMCs from patients was 20.44 times of that from the controls.The total serum IgE level was 260.05 IU/mL(5.9-1131.01 IU/mL)and 17.7 IU/mL(5-140.7 IU/mL)in the Patients and controls respectively(P＜0.01).There was no significant correlation between the mRNA expression of IL-31 and disease severity or total serum IgE level(r=0.07.0.22respectively.both P＞0.05)in patients witll AD.Condusions IL.3 1 is involved in t11e pathogenesis of AD,which is unlikely to be IgE-dependent.SEB can induce the rapid expression of IL-31 on PBMCs of healthy human,and is an important modulator for the production of IL-31.