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1.
Bioorg Med Chem Lett ; 82: 129149, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36690039

RESUMO

A series of 1-O-acyl- and 1-oxo-kamebanin analogues were prepared from kamebanin, isolated from Rabdosia excisa and their cytotoxicity was assayed on HL60 promyelocytic leukemia cells and HCT116 human colon cancer cells. The structure-activity relationship study showed that the presence of 1-O-acyl groups of a C3-C5 carbon chain increased the cytotoxic activity.


Assuntos
Antineoplásicos , Isodon , Humanos , Antineoplásicos/farmacologia , Relação Estrutura-Atividade , Células HL-60 , Células HCT116
2.
Int J Mol Sci ; 23(10)2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35628261

RESUMO

The relationship between transcription and aging is one that has been studied intensively and experimentally with diverse attempts. However, the impact of the nuclear mRNA export on the aging process following its transcription is still poorly understood, although the nuclear events after transcription are coupled closely with the transcription pathway because the essential factors required for mRNA transport, namely TREX, TREX-2, and nuclear pore complex (NPC), physically and functionally interact with various transcription factors, including the activator/repressor and pre-mRNA processing factors. Dysregulation of the mediating factors for mRNA export from the nucleus generally leads to the aberrant accumulation of nuclear mRNA and further impairment in the vegetative growth and normal lifespan and the pathogenesis of neurodegenerative diseases. The optimal stoichiometry and density of NPC are destroyed during the process of cellular aging, and their damage triggers a defect of function in the nuclear permeability barrier. This review describes recent findings regarding the role of the nuclear mRNA export in cellular aging and age-related neurodegenerative disorders.


Assuntos
Núcleo Celular , Transporte de RNA , Transporte Ativo do Núcleo Celular/genética , Núcleo Celular/metabolismo , Poro Nuclear/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
3.
Int J Mol Sci ; 23(14)2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35887370

RESUMO

Since the discovery of the small ubiquitin-like modifier (SUMO) protein in 1995, SUMOylation has been considered a crucial post-translational modification in diverse cellular functions. In neurons, SUMOylation has various roles ranging from managing synaptic transmitter release to maintaining mitochondrial integrity and determining neuronal health. It has been discovered that neuronal dysfunction is a key factor in the development of major depressive disorder (MDD). PubMed and Google Scholar databases were searched with keywords such as 'SUMO', 'neuronal plasticity', and 'depression' to obtain relevant scientific literature. Here, we provide an overview of recent studies demonstrating the role of SUMOylation in maintaining neuronal function in participants suffering from MDD.


Assuntos
Transtorno Depressivo Maior , Sumoilação , Transtorno Depressivo Maior/metabolismo , Humanos , Neurônios/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo
4.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065586

RESUMO

Depression is a highly prevalent, disabling, and often chronic illness that places substantial burdens on patients, families, healthcare systems, and the economy. A substantial minority of patients are unresponsive to current therapies, so there is an urgent need to develop more broadly effective, accessible, and tolerable therapies. Pharmacological regulation of histone acetylation level has been investigated as one potential clinical strategy. Histone acetylation status is considered a potential diagnostic biomarker for depression, while inhibitors of histone deacetylases (HDACs) have garnered interest as novel therapeutics. This review describes recent advances in our knowledge of histone acetylation status in depression and the therapeutic potential of HDAC inhibitors.


Assuntos
Depressão/genética , Epigênese Genética/genética , Histona Desacetilases/genética , Acetilação/efeitos dos fármacos , Animais , Epigenômica/métodos , Inibidores de Histona Desacetilases/farmacologia , Humanos
5.
Exp Dermatol ; 28(3): 300-307, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30688372

RESUMO

There is an unmet need in novel therapeutics for atopic dermatitis (AD). We examined the effects of autologous adipose-derived stem cells (ADSCs) on AD-like skin lesions induced by the application of 2,4-dinitrochlorobenzene (DNCB) in NC/Nga mice. Autologous ADSCs and ADSC-conditioned medium (ADSC-CM) were injected intralesionally three times. Clinical severity and histopathologic findings were compared in sham naïve control, saline-treated, ADSC-treated, ADSC-CM-treated and 2.5% cortisone lotion-applied animals. The severity index, skin thickness, mast cell number, as well as expression levels of thymic stromal lymphopoietin, CD45, chemoattractant receptor-homologous molecule, chemokine ligand 9 and chemokine ligand 20 were significantly lower in mice treated with ADSC, ADSC-CM, or 2.5% cortisone lotion. Tissue levels of interferon-γ as well as serum levels of interleukin-33 and immunoglobulin E levels were also decreased in those groups. We conclude that autologous ADSCs improved DNCB-induced AD-like skin lesions in NC/Nga mice by reducing inflammation associated with Th2 immune response and interferon-γ.


Assuntos
Adipócitos/citologia , Dermatite Atópica/terapia , Transplante de Células-Tronco , Células-Tronco/citologia , Tecido Adiposo/citologia , Animais , Transplante de Células , Quimiocina CCL20/metabolismo , Quimiocina CXCL2/metabolismo , Cortisona/farmacologia , Meios de Cultivo Condicionados , Citocinas/metabolismo , Eczema/metabolismo , Imunoglobulina E/metabolismo , Inflamação , Injeções Subcutâneas , Interferon gama/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Masculino , Camundongos , Receptores Imunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Pele/metabolismo , Células Th2/citologia , Linfopoietina do Estroma do Timo
6.
Acta Derm Venereol ; 99(1): 41-46, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30281139

RESUMO

Treatment of alopecia totalis and alopecia universalis is often challenging and unsatisfactory. Recently, Janus kinase inhibitor has shown promising results. The aim of this study is to compare the efficacy and tolerability of oral tofacitinib and conventional modalities for treating refractory alopecia totalis/universalis. A total of 74 patients (18 treated with tofacitinib, 26 treated with conventional oral treatment (steroid ± cyclosporine), and 30 treated with diphenylcyclopropenone) were included in the study. The patients' medical records were reviewed retrospectively. After 6 months, 44.4% of patients in the tofacitinib group, 37.5% in the conventional oral treatment group, and 11.1% in the diphenylcyclopropenone group achieved 50% improvements in the Severity of Alopecia Tool score. During treatment, 10% of patients in the tofacitinib group, 73.1% in the conventional oral treatment group, and 10% in the diphenylcyclopropenone group experienced adverse drug reactions. In conclusion, oral tofacitinib was more effective than diphenylcyclopropenone immunotherapy and more tolerable than conventional oral treatment after 6 months of treatment.


Assuntos
Alopecia/tratamento farmacológico , Inibidores de Janus Quinases/administração & dosagem , Piperidinas/administração & dosagem , Pirimidinas/administração & dosagem , Pirróis/administração & dosagem , Administração Oral , Adolescente , Adulto , Alopecia/diagnóstico , Alopecia/imunologia , Ciclopropanos/administração & dosagem , Ciclosporina/administração & dosagem , Feminino , Humanos , Imunossupressores/administração & dosagem , Inibidores de Janus Quinases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Pirimidinas/efeitos adversos , Pirróis/efeitos adversos , Estudos Retrospectivos , Esteroides/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
7.
Exp Dermatol ; 27(1): 43-49, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28677206

RESUMO

Previous studies have shown that imiquimod-induced psoriasis-like skin inflammation in mice resembles phenotypic changes and cytokine profiles of human psoriasis. However, a psoriasis animal model reflecting the chronic inflammatory course and comorbidities has not yet been established. We aimed to evaluate the imiquimod-applied interleukin (IL)-10 deficient mouse model in comparison with previous models. IL-10 deficient and wild-type (WT) mice received either imiquimod or vehicle cream for 12 days and were sacrificed on day 15. For earlier time point data, either imiquimod or vehicle cream was applied for 2 days, and the mice were sacrificed on day 3. Imiquimod-applied IL-10 deficient mice showed more persistent psoriasis-like inflammation and higher severity index than did WT between day 8 and 15. Histopathologically, they demonstrated significantly thicker epidermis and larger number of CD45+, myeloperoxidase+ and IL-17+ cell counts on day 15. Quantitative reverse transcription-polymerase chain reaction with skin tissue revealed significantly higher imiquimod-induced IL-23p19 expression in imiquimod-applied IL-10 deficient mice on day 15. IL-10 deficient mice also showed significantly higher serum levels of imiquimod-induced IL-17A and tumor necrosis factor-α by enzyme-linked immunosorbent assay on day 15. Furthermore, IL-10 deficient mice showed more prominent increase of spleen weight and decrease of body weight in response to imiquimod application on day 3 and 15. In conclusion, IL-10 deficient mice model with imiquimod application may better reflect severe and persistent psoriasis with systemic inflammatory state.


Assuntos
Imiquimode/farmacologia , Inflamação/metabolismo , Interleucina-10/genética , Psoríase/tratamento farmacológico , Adjuvantes Imunológicos/farmacologia , Animais , Peso Corporal , Citocinas/metabolismo , Dermatite/metabolismo , Modelos Animais de Doenças , Epiderme/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Queratinócitos/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão , Psoríase/metabolismo , RNA Mensageiro/metabolismo , Pele/metabolismo , Pele/patologia , Baço/patologia , Fatores de Tempo
8.
J Am Acad Dermatol ; 79(2): 315-319, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29128460

RESUMO

BACKGROUND: The appropriate classification of study designs is important for review and assessment of the relevant scientific literature as a basis for decision making; however, little is known about whether study designs have been appropriately reported in the dermatology literature. OBJECTIVE: We aimed to validate the study designs in the dermatology literature and investigate discrepancies between author-reported and actual study designs. METHODS: We reviewed all issues of 3 major dermatology journals from January to December 2016. A total of 295 original articles investigating associations between exposures and health outcomes were included for analysis. We used a validated algorithm to classify the study designs. RESULTS: Among the 295 articles, 174 (59.0%) clearly mentioned the study design in the text. All interventional studies were correctly classified on the basis of study design (n = 42); however, 35 of 132 observational studies (26.5%) showed discrepancies between the author-reported and actual study design. When the author-reported design was a prospective cohort, retrospective cohort, or case-control study (n = 61), approximately half of the studies were misclassified by the authors (n = 30). LIMITATIONS: We analyzed only 3 journals in the dermatology field. CONCLUSIONS: Our findings revealed substantial discrepancies between author-reported and actual study designs in the dermatologic literature, particularly among observational studies.


Assuntos
Pesquisa Biomédica/classificação , Dermatologia , Projetos de Pesquisa , Algoritmos , Humanos , Relatório de Pesquisa
9.
J Nanosci Nanotechnol ; 18(3): 2140-2143, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29448731

RESUMO

In this paper, we discuss the effect of synthesis temperature on the lateral growth of MoS2 thin films in chemical vapor deposition. With increasing temperature, surface coverage with MoS2 triangular islands is significantly improved due to an increase in the density of nuclei and fully continuous MoS2 thin film is grown when the growth temperature reached 800 °C. The MoS2 triangular islands grown at the temperature from 650 to 750 °C are monolayer and highly crystalline, whereas the large-area continuous film grown at the temperature of 800 °C is composed of double-layer or overlapping MoS2 nanosheets. Our research provides that synthesis temperature is the key to growth large area and high quality single crystal MoS2 films.

10.
Biochem Biophys Res Commun ; 469(2): 216-21, 2016 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-26655814

RESUMO

Glucagon-like peptide-1 (GLP-1) is a gut peptide that promotes insulin release from pancreatic beta cells. GLP-1 has been shown to confer glucose-insensitive beta cells with glucose sensitivity by modulation of the activity of the ATP-sensitive potassium (KATP) channel. The channel closing effect of GLP-1, interacting with corresponding G-protein-coupled receptors, has been well established; however, to our knowledge, no study has shown whether GLP-1 directly induces activation of beta-cell KATP channels. Here, we aimed to evaluate whether the activation of beta-cell KATP channels by GLP-1 exists and affects intracellular Ca(2+) levels ([Ca(2+)]i). KATP channel activity was measured in isolated rat pancreatic beta cells by whole-cell perforated patch-clamp recordings with a diazoxide-containing pipette solution. Changes in [Ca(2+)]i and the subcellular localization of KATP channels were observed using the calcium-sensitive dye fura-4/AM and anti-Kir6.2 antibodies in INS-1 beta cells, respectively. To eliminate the well-known inhibitory effects of GLP-1 on KATP channel activity, channels were fully inhibited by pretreatment with methyl pyruvate and epigallocatechin-3-gallate. In the pretreated beta cells, GLP-1 and exendin-4 promptly activated the channels, reducing [Ca(2+)]i. The phosphoinositide 3-kinase (PI3K) inhibitor LY294002 blocked the effects of GLP-1 on channel activity. Moreover, phosphatidylinositol-3,4,5-trisphosphate mimicked the effects of GLP-1. These results suggested that beta-cell GLP-1 receptor signaling involved activation of KATP channels via a PI3K-dependent pathway. This alternative mechanism of GLP-1 function may act as a negative feedback pathway, modulating the glucose-dependent GLP-1 inhibition on KATP channel activity.


Assuntos
Cálcio/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Células Secretoras de Insulina/fisiologia , Ativação do Canal Iônico/fisiologia , Canais KATP/fisiologia , Transdução de Sinais/fisiologia , Animais , Linhagem Celular , Ratos
11.
Phytother Res ; 30(10): 1689-1695, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27388056

RESUMO

In the fasting state, gluconeogenesis is upregulated by glucagon. Glucagon stimulates cyclic adenosine monophosphate production, which induces the expression of key enzymes for gluconeogenesis, such as cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), which are involved in gluconeogenesis through the protein kinase A/cAMP response element-binding protein (CREB) pathway. Using a luciferase reporter gene assay, a methanol extract of the bulbs of Lycoris sanguinea MAXIM. var. kiushiana Makino was found to suppress cAMP-enhanced PEPCK-C promoter activity. In addition, two alkaloids, lycoricidine and lycoricidinol, in the extract were identified as active constituents. In forskolin-stimulated human hepatoma cells, these alkaloids suppressed the expression of a reporter gene under the control of cAMP response element and also prevented increases in the endogenous levels of phosphorylated CREB and PEPCK mRNA expression. These results suggest that lycoricidine and lycoricidinol suppress PEPCK-C expression by inhibiting the phosphorylation of CREB and may thus have the potential to prevent excessive gluconeogenesis in type 2 diabetes. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/antagonistas & inibidores , Lycoris/química , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , Alcaloides , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Gluconeogênese , Humanos , Fosforilação , Transfecção
12.
Langmuir ; 31(6): 1950-7, 2015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25635466

RESUMO

For several decades, evaporation phenomena have been intensively investigated for a broad range of applications. However, the dynamics of contact line depinning during droplet evaporation has only been inductively inferred on the basis of experimental data and remains unclear. This study focuses on the dynamics of contact line depinning during droplet evaporation based on thermodynamics. Considering the decrease in the Gibbs free energy of a system with different evaporation modes, a theoretical model was developed to estimate the receding contact angle during contact line depinning as a function of surface conditions. Comparison of experimentally measured and theoretically modeled receding contact angles indicated that the dynamics of contact line depinning during droplet evaporation was caused by the most favorable thermodynamic process encountered during constant contact radius (CCR mode) and constant contact angle (CCA mode) evaporation to rapidly reach an equilibrium state during droplet evaporation.

13.
Dermatol Ther ; 28(5): 287-90, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25845419

RESUMO

Livedoid vasculopathy (LV) is a thrombotic vasculopathy of the skin of unknown origin. No treatment has been validated in this indication, but case reports demonstrated successful use of intravenous immunoglobulins (IVIg) in LV. We assessed the efficacy and tolerability of 2 g/kg IVIg therapy every month for 2∼3 cycles in patients with refractory LV. We analyzed the efficacy, side effects and recurrence after long-term follow-up (51.9 ± 14.0 months) in seven patients with LV treated with 2 g/kg of IVIg. Mean clinical score of sum of erythema, ulceration and pain index (each: 0-3) was 5.7 ± 0.9 before the therapy and significantly lower after therapy (1.1 ± 0.5) (p = 0.001). Even after just one cycle of IVIg, the score decreased significantly from 5.7 ± 0.9 to 3.7 ± 0.9 (p = 0.002), especially the pain score. In one patient, LV has not recurred for over 7 years; six patients experienced recurrence after a mean of 12.7 ± 2.8 months. Out of the six patients, two patients were re-administered IVIg whereas the others were well controlled by conventional therapy. We propose that IVIg is a rapid, effective, and safe therapeutic option in LV refractory to other treatment modalities.


Assuntos
Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Livedo Reticular/tratamento farmacológico , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Fatores Imunológicos/efeitos adversos , Livedo Reticular/imunologia , Livedo Reticular/patologia , Masculino , Pulsoterapia , Recidiva , Retratamento , Resultado do Tratamento , Adulto Jovem
14.
Acta Derm Venereol ; 95(6): 696-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25572793

RESUMO

To determine which patient and maternal factors are associated with the occurrence and the severity of infantile haemangioma (IH), a single-centre retrospective observational study was conducted with 96 haemangioma patients and 143 age-matched control babies, born in the same hospital between March 2012 and March 2013. The IH patients were selected according to diagnosis from dermatologists, either consulted from the department of paediatrics or in outpatient setting. Unplanned female children whose mothers smoked and/or consumed alcohol when pregnant was more likely to have IH (p < 0.0.05). The higher the birth weight, the more superficial the haemangioma (p = 0.023), and localised lesions were more common in singleton babies (p = 0.023) and babies conceived by normal fertilisation (p = 0.002). The occurrence and severity of IH is not only influenced by patient factors but also by maternal factors especially care during pregnancy period. By controlling these factors, the incidence and severity of IH may be lowered.


Assuntos
Consumo de Bebidas Alcoólicas , Peso ao Nascer , Hemangioma Capilar/epidemiologia , Síndromes Neoplásicas Hereditárias/epidemiologia , Fumar , Pré-Escolar , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Gravidez , Gravidez não Planejada , Cuidado Pré-Natal , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais
15.
Dermatol Surg ; 41(8): 960-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26218729

RESUMO

BACKGROUND: Recently, rimabotulinumtoxinB has been increasingly used as an off-label treatment of primary axillary hyperhidrosis (PAH). However, the optimal conversion ratios for onabotulinumtoxinA and rimabotulinumtoxinB remain to be determined. OBJECTIVE: To compare effectiveness, satisfaction level, and safety of rimabotulinumtoxinB with onabotulinumtoxinA at a conversion ratio of 1:30 for the treatment of PAH. METHODS: Adults with PAH were enrolled in this bilaterally paired single-subject study. Each patient was randomly treated with 1,500 U rimabotulinumtoxinB on 1 axilla and 50 U onabotulinumtoxinA contralaterally. Hyperhidrosis Disease Severity Scale was assessed before and after treatment up to 20 weeks. A 10-cm visual analog scale representing improvement of hidrotic symptom and starch-iodine test were also used to assess therapeutic efficacy. RESULTS: Twenty-four patients completed the study. Both groups showed comparable and efficacious anhidrotic effects through 20 weeks for any variable. There were no significant differences in terms of the onset of action or mean duration of action between the 2 groups. Overall satisfaction with the treatment was equally high in both groups. CONCLUSION: Both toxins showed comparable anhidrotic effect for the treatment of axillary hyperhidrosis at a conversion ratio of 1:30.


Assuntos
Inibidores da Liberação da Acetilcolina/uso terapêutico , Toxinas Botulínicas Tipo A/uso terapêutico , Hiperidrose/tratamento farmacológico , Inibidores da Liberação da Acetilcolina/efeitos adversos , Adulto , Axila , Toxinas Botulínicas Tipo A/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Escala Visual Analógica , Adulto Jovem
16.
Exp Dermatol ; 23(8): 591-5, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24962024

RESUMO

Toll-like receptors (TLRs) mediate not only innate immunity against infection and but also sterile inflammation triggered by endogenous molecules. We conducted a comparative study of the different inflammatory responses induced by repetitive ultraviolet (UV) B irradiation in wild-type (WT) and TLR2 knockout (KO) mice, to provide in vivo evidence of the role of TLRs in mediating UVB-induced responses. UVB-induced inflammatory responses were less severe in TLR2 KO mice than in WT mice after 6 weeks of repeated UVB irradiation. UVB-treated TLR2 KO mice displayed less prominent erythema and scaling, and histopathology showed significantly thinner skin and less inflammatory cell infiltration than that in WT mice. UVB-induced expression of heat-shock protein 70 (an endogenous ligand of TLR2) was lower in TLR2 KO mice. Quantitative RT-PCR revealed significantly lower gene expression levels of UVB-induced interleukin (IL)-1ß, IL-6 and matrix metalloproteinase (MMP)-13 in TLR2 KO mice. TLR2 KO mice also showed significantly lower protein level expression of UVB-induced IL-1ß in ELISA and MMP-13 in Western blots. Our study demonstrated that TLR2 was associated with inflammatory responses to repetitive UVB irradiation in C57/BL6 mice. Moreover, it suggests that the role of TLR2 in the cutaneous response of UV irradiation and in developing new agents for modulating the effects of UV irradiation should be considered.


Assuntos
Inflamação/metabolismo , Pele/metabolismo , Pele/efeitos da radiação , Receptor 2 Toll-Like/metabolismo , Raios Ultravioleta/efeitos adversos , Animais , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Proteínas de Choque Térmico HSP70/metabolismo , Inflamação/etiologia , Inflamação/patologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pele/patologia , Receptor 2 Toll-Like/deficiência , Receptor 2 Toll-Like/genética
17.
NPJ Vaccines ; 9(1): 108, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879560

RESUMO

Alzheimer's disease (AD) and related tauopathies are associated with pathological tau protein aggregation, which plays an important role in neurofibrillary degeneration and dementia. Targeted immunotherapy to eliminate pathological tau aggregates is known to improve cognitive deficits in AD animal models. The tau repeat domain (TauRD) plays a pivotal role in tau-microtubule interactions and is critically involved in the aggregation of hyperphosphorylated tau proteins. Because TauRD forms the structural core of tau aggregates, the development of immunotherapies that selectively target TauRD-induced pathological aggregates holds great promise for the modulation of tauopathies. In this study, we generated recombinant TauRD polypeptide that form neurofibrillary tangle-like structures and evaluated TauRD-specific immune responses following intranasal immunization in combination with the mucosal adjuvant FlaB. In BALB/C mice, repeated immunizations at one-week intervals induced robust TauRD-specific antibody responses in a TLR5-dependent manner. Notably, the resulting antiserum recognized only the aggregated form of TauRD, while ignoring monomeric TauRD. The antiserum effectively inhibited TauRD filament formation and promoted the phagocytic degradation of TauRD aggregate fragments by microglia. The antiserum also specifically recognized pathological tau conformers in the human AD brain. Based on these results, we engineered a built-in flagellin-adjuvanted TauRD (FlaB-TauRD) vaccine and tested its efficacy in a P301S transgenic mouse model. Mucosal immunization with FlaB-TauRD improved quality of life, as indicated by the amelioration of memory deficits, and alleviated tauopathy progression. Notably, the survival of the vaccinated mice was dramatically extended. In conclusion, we developed a mucosal vaccine that exclusively targets pathological tau conformers and prevents disease progression.

18.
Dermatol Surg ; 39(10): 1520-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24090262

RESUMO

BACKGROUND: Pincer nails are characterized by the transverse curvature increasing from the proximal to the distal aspect along the longitudinal axis. A novel treatment technique using a shape memory alloy device was recently introduced. OBJECTIVE: To determine the treatment outcomes and safety of a shape memory alloy device. METHODS AND MATERIALS: This was a retrospective analysis of 21 cases of pincer nail of the great toe in 14 patients. Subjective indices (pain, inconvenience, global assessment scores) and objective parameters (transverse angle, width index) on days 0 (D0) and 1 (D1) and weeks 2 (W2) and 12 (W12) were investigated. RESULTS: All parameters started to show significant improvement on D1. From D0 to D1, pain score fell from 3.6 ± 1.0 to 1.5 ± 0.7, inconvenience score fell from 3.3 ± 1.0 to 1.5 ± 0.7, global assessment score increased from 1.5 ± 0.7 to 2.5 ± 0.7, transverse angle improved from 86.4 ± 27.7° to 114.7 ± 21.6°, and width index improved from 67.6 ± 13.1% to 89.0 ± 9.7%. These effects were consistent during 12 weeks of follow-up. Two cases (9.5%) recurred, but symptoms were less severe than before. No complication was identified. CONCLUSION: A shape memory alloy device was an effective and safe way to rapidly correct symptomatic pincer nail deformity.


Assuntos
Unhas Malformadas/terapia , Próteses e Implantes , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Unhas Malformadas/complicações , Unhas Malformadas/patologia , Dor/etiologia , Próteses e Implantes/efeitos adversos , Qualidade de Vida , Recidiva , Estudos Retrospectivos , Adulto Jovem
20.
Int J Med Sci ; 9(1): 83-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22211094

RESUMO

Pacinian corpuscles are sensory nerve-end organs located in the deep dermis and subcutaneous tissue of the palms or soles. Pacinian neuroma is an extremely rare feature, defined as hyperplasia or hypertrophy of Pacinian corpuscles. About half of Pacinian neuromas present with point tenderness. There have been a limited number of cases reported around the world. We observed a 45-year-old woman with an 8-month history of a tender whitish papule on her left thumb tip. Histopathologically, an enlarged hypertrophic Pacinian corpuscle in subcutaneous tissue, surrounded by numerous nerve fibers, was found. Herein, we report a case of Pacinian neuroma presenting as a tender papule on a fingertip that was clearly related to repetitive trauma at that site. This case shows that a meticulous history and histological examination can lead to an exact diagnosis and proper treatment.


Assuntos
Neuroma/diagnóstico , Neuroma/patologia , Corpúsculos de Pacini/patologia , Polegar/patologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Fibras Nervosas , Neuroma/etiologia , Tela Subcutânea/patologia , Polegar/inervação , Ferimentos e Lesões/complicações , Ferimentos e Lesões/diagnóstico
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