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1.
J Invest Dermatol ; 143(8): 1439-1448.e21, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36804966

RESUMO

The discovery of pathogenic variants provided biological insight into the role of host genetic factors in generalized pustular psoriasis (GPP). However, not all those affected by GPP carry variants in the reported genes. To comprehensively explore the molecular pathogenesis of GPP, whole-exome sequencing was performed, and two loci were identified with exome-wide significance through single variant association analysis: rs148755083 in the IL36RN gene (Pcombined = 1.19 × 10-18, OR = 8.26) and HLA-C∗06:02 within the major histocompatibility complex region (Pcombined = 8.38 × 10-12, OR = 2.98). Gene burden testing revealed that BTN3A3 correlated with GPP (Pcombined = 1.14 × 10-10, OR = 5.59). Subtype analysis showed that IL36RN and BTN3A3 were both significantly associated with GPP alone and GPP with psoriasis vulgaris, whereas a correlation with HLA-C∗06:02 was only observed in GPP with psoriasis vulgaris. Functional analysis revealed that BTN3A3 regulated cell proliferation and inflammatory balance in GPP. In particular, loss of function of BTN3A3 activated NF-κB and promoted the production of inflammatory cytokines by inhibiting IL-36Ra expression to disturb the IL-1/IL-36 inflammatory axis and enhance the TNF-α-mediated pathway. Our findings identify BTN3A3 as, to our knowledge, a previously unreported pathogenic determinant, expanding our understanding of the genetic basis of GPP.


Assuntos
Psoríase , Dermatopatias Vesiculobolhosas , Humanos , População do Leste Asiático , Testes Genéticos , Antígenos HLA-C/genética , Interleucinas/genética , Psoríase/genética , Psoríase/patologia , Dermatopatias Vesiculobolhosas/genética , Butirofilinas/genética
2.
Front Med (Lausanne) ; 9: 933608, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36203762

RESUMO

Common autoimmune bullous diseases (AIBDs) include pemphigus and bullous pemphigoid (BP), which are primarily caused by IgG autoantibodies against the structural proteins of desmosomes at the cell-cell junction and hemidesmosomes at the epidermal-dermal junction. Few studies have assessed nail changes in patients with pemphigus or BP. In the present study, we collected the clinical data of 191 patients with AIBDs (108 patients with pemphigus and 83 patients with BP) and 200 control subjects. Nail changes were observed in 77.0% (147/191), 77.8% (84/108), and 75.9% (63/83) of patients with AIBDs, pemphigus, and BP, respectively, and 14.5% (29/200) of control subjects. Beau's lines and paronychia were the most common nail involvement, observed in 22.5% (43/191) and 22.5% (43/191) of patients with AIBDs, 25.0% (27/108) and 25.9% (28/108) of patients with pemphigus, 19.3% (16/83) and 18.1% (15/83) of patients with BP, respectively. The autoimmune bullous skin disorder intensity score (ABSIS) and the onset time of patients with pemphigus or BP with nail changes were different. Onychomycosis accounted for 21.5% (41/191) of all patients with AIBDs. The ABSIS was correlated with nail involvement in patients with BP (r = 0.46, p < 0.001), and weakly correlated with nail involvement in patients with AIBDs (r = 0.37, p < 0.001), pemphigus (r = 0.29, p = 0.009), and pemphigus vulgaris (PV; r = 0.35, p = 0.008). No correlation was observed between nail involvement and disease antibody titers. In conclusion, nail changes are frequently observed in patients with pemphigus and BP. The type and onset time of nail changes may indicate the severity of pemphigus and BP, which warrants the attention of dermatologists.

3.
Int J Pharm ; 588: 119759, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32800938

RESUMO

The purpose of this study is to improve in vitro dissolution and in vivo bioavailability of the poorly soluble drug cilostazol (CLT) through amorphous solid dispersion technology, and this study prepared a stable supersaturated drug-loaded system to improve the problem of high free energy and instability of traditional solid dispersions. The optimized formulation of the solid dispersion is CLT: Syloid®244FP: Kolliphor®P188 = 1:1.5:1.5 (CLT-SD), where the co-loading of Syloid®244FP and Kolliphor®P188 has the synergistic effect. Drug polymers interactions and drug morphology were estimated by the physicochemical characterization, including DSC XRD, SEM, TEM, FT-IR, and Specific area analysis. Optimized formulation kept most drug in an amorphous state without significant change in dissolution, which could be maintained for at least 1 year. The solid dispersion was further prepared into osmotic pump tablets for the purpose of the controlled-release of drugs. The bioavailability of the three preparations (CLT, CLT-SD, osmotic pump tablets) was evaluated in Beagle dogs, which results clarified that the oral bioavailability of CLT-SD improved as compared with the CLT powder and osmotic pump tablets achieved controlled-release of drugs. In conclusion, co-loading drugs with mesoporous silica and hydrophilic polymer compounds can be a guiding future modification method for delivering supersaturated drug loading systems.


Assuntos
Cilostazol , Polímeros , Dióxido de Silício , Animais , Disponibilidade Biológica , Cães , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Comprimidos
4.
Opt Express ; 27(5): 6370-6376, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30876223

RESUMO

The research of Airy beams has attained much attention due to their unique characteristics. Coherent control of Airy beams is important for further light beam manipulation and information processing. In this paper, we experimentally investigate the storage and retrieval of 2D Airy wavepackets in a solid-state medium driven by electromagnetically induced transparency (EIT). The transverse profile of the weak probe pulse is modulated by Airy wavepackets. Under EIT condition, the probe Airy wavepackets are stored into the experimental medium by manipulating the intensity of the control field, and later retrieved by the opposite process. The retrieved Airy wavepackets keep a high similarity compared with those before the storage. Furthermore, the self-healing property of the retrieved Airy wavepackets is investigated. This storage of Airy wavepackets develops the control method of Airy beams, which will be useful in further applications.

5.
Sci Rep ; 5: 18179, 2015 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-26658846

RESUMO

Coherent storage of optical image in a coherently-driven medium is a promising method with possible applications in many fields. In this work, we experimentally report a controllable spatial-frequency routing of image via atomic spin coherence in a solid-state medium driven by electromagnetically induced transparency (EIT). Under the EIT-based light-storage regime, a transverse spatial image carried by the probe field is stored into atomic spin coherence. By manipulating the frequency and spatial propagation direction of the read control field, the stored image is transferred into a new spatial-frequency channel. When two read control fields are used to retrieve the stored information, the image information is converted into a superposition of two spatial-frequency modes. Through this technique, the image is manipulated coherently and all-optically in a controlled fashion.

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