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1.
J Psychiatr Ment Health Nurs ; 31(1): 31-42, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37485769

RESUMO

INTRODUCTION: A culturally adaptive and easy-to-administer 12-item Caregiving Rewarding Feelings (CRF) scale has been developed in China yet never published in English and validated in another population. AIM: The current study aimed to validate the CRF among a community sample of Chinese caregivers of those diagnosed with schizophrenia. METHOD: A sample of 449 family caregivers was recruited for scale validation that included factorial validity, construct validity, measurement invariance, item analysis, internal consistency reliability, test-retest reliability, known-group validity, convergent validity and divergent validity. RESULTS: Confirmatory factor analysis supported the a priori three-factor structure. Construct validity was supported by high standard regression weight (SRW) and average variance extracted (AVE), measurement invariance across age and gender groups. The CRF showed good internal consistency and test-retest reliability. Known-group validity was confirmed by the higher CRF scores among caregivers with certain socio-demographics. The convergent validity of the CRF was supported by its positive correlations with social support, active coping and family functioning. The divergent validity of the CRF was supported by its negative associations with stigma, stress and depressive symptoms. CONCLUSIONS: This study confirmed the reliability and validity of the CRF specifically designed for caregivers in Chinese culture. IMPLICATIONS FOR PRACTICE: The CRF may be further applied and validated in other populations and other countries.


Assuntos
Cuidadores , Esquizofrenia , Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Psicometria , China
2.
Heliyon ; 9(9): e20186, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809588

RESUMO

Background and aim: Melasma (ML), naevus fusco-caeruleus zygomaticus (NZ), freckles (FC), cafe-au-lait spots (CS), nevus of ota (NO), and lentigo simplex (LS), are common skin diseases causing hyperpigmentation. Deep learning algorithms learn the inherent laws and representation levels of sample data and can analyze the internal details of the image and classify it objectively to be used for image diagnosis. However, deep learning algorithms that can assist clinicians in diagnosing skin hyperpigmentation conditions are lacking. Methods: The optimal deep-learning image recognition algorithm was explored for the auxiliary diagnosis of hyperpigmented skin disease. Pretrained models, such as VGG-19, GoogLeNet, InceptionV3, ResNet50V2, ResNet101V2, ResNet152V2, InceptionResNetV2, DesseNet201, MobileNet, and NASNetMobile were used to classify images of six common hyperpigmented skin diseases. The best deep learning algorithm for developing an online clinical diagnosis system was selected by using accuracy and area under curve (AUC) as evaluation indicators. Results: In this research, the parameters of the above-mentioned ten deep learning algorithms were 18333510, 5979702, 21815078, 23577094, 42638854, 58343942, 54345958, 18333510, 3235014, and 4276058, respectively, and their training time was 380, 162, 199, 188, 315, 511, 471, 697, 101, and 144 min respectively. The respective accuracies of the training set were 85.94%, 99.72%, 99.61%, 99.52%, 99.52%, 98.84%, 99.61%, 99.13%, 99.52%, and 99.61%. The accuracy rates of the test set data were 73.28%, 57.40%, 70.04%, 71.48%, 68.23%, 71.11%, 71.84%, 73.28%, 70.39%, and 43.68%, respectively. Finally, the areas of AUC curves were 0.93, 0.86, 0.93, 0.91, 0.91, 0.92, 0.93, 0.92, 0.93, and 0.82, respectively. Conclusions: The experimental parameters, training time, accuracy, and AUC of the above models suggest that MobileNet provides a good clinical application prospect in the auxiliary diagnosis of hyperpigmented skin.

3.
Eur J Clin Invest ; 53(6): e13959, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36708067

RESUMO

BACKGROUND: Psoriasis is a classic chronic recurrent inflammatory skin disease characterized by skin inflammation and abnormal biological behaviour of keratinocytes. Although Signal Transducer And Activator Of Transcription 2 (STAT2) was found to play an important role in the Janus kinase (JAK)-STAT signalling pathway and contribute to the pathogenesis of psoriasis, its exact role in psoriasis remains unclear. METHODS: Using bioinformatics analysis, we identified the key pathways that significantly impacted psoriatic lesions. After identifying the critical molecule gene differentially expressed in multiple public databases using the Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis, clinical samples were collected to validate the gene's significance. Its functions and underlying mechanism were also investigated in vitro. Lastly, we evaluated the diagnostic and therapeutic power of the target gene using the receiver operating characteristic curve (ROC), and gene association was assessed using Spearman correlation. RESULTS: A significant correlation was found between cysteine-aspartic acid protease3 (Caspase3) and STAT2, and functional enrichment analysis revealed that they were both significantly up-regulated in psoriatic skin lesions compared to non-lesional tissues. Functional analysis revealed that Caspase3 functioned downstream of STAT2 in psoriasis. Lastly, we found that Caspase3 and STAT2 could be potential biomarkers for diagnosing and treating psoriasis. CONCLUSIONS: In summary, STAT2 overexpression contributes to psoriasis progression by regulating Capase3 phosphorylation to induce excessive apoptosis of keratinocytes. Meanwhile, STAT2 and Capase3 were identified as promising biomarkers for the diagnosis and treatment of psoriasis and could be used for individualized treatments.


Assuntos
Psoríase , Humanos , Fator de Transcrição STAT2/genética , Fator de Transcrição STAT2/metabolismo , Psoríase/diagnóstico , Psoríase/genética , Psoríase/tratamento farmacológico , Pele/metabolismo , Queratinócitos/metabolismo , Queratinócitos/patologia , Biomarcadores/metabolismo
4.
Mol Immunol ; 151: 1-10, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36058047

RESUMO

Diseases with T-helper cell subset imbalance involve multiple systems and organs. In addition to this, the pathogenesis of these diseases is always complex, and involves Th1, Th2, Th9, Th17, Th22, and Tfh cells. T-helper cell subset imbalance mediates immune responses to various pathogenic factors, by secreting specific cytokines. Although several studies have revealed the specific mechanisms of the occurrence and development of these diseases from different aspects, there is still a need for more comprehensive and in-depth studies that can compensate for the corresponding gaps in the diagnosis, targeted therapy, and prognosis of these diseases. N6-methyladenosine(m6A) modification is the most prevalent and abundant post-transcriptional modification in eukaryotic RNAs. In recent years, the critical role of m6A modification has been confirmed in multiple diseases with T-helper cell subset imbalance. m6A modification affects the immune cell development, inflammatory processes, biological behaviour of tumours, and immune response in these diseases. In this review, we focussed on how the enzymes involved in m6A modification, directly or indirectly, influence the pathogenesis and phenotype of various diseases with T-helper cell subset imbalance, and could therefore, serve as potential diagnostic markers and therapeutic targets for these diseases. In addition, this review also discusses the focus of future research in this area. Finally, we summarise the prospects of m6A modification in immunotherapy and chemotherapy.


Assuntos
Linfócitos T Auxiliares-Indutores , Células Th17 , Diferenciação Celular , Citocinas , Células Th1 , Células Th2
5.
Exp Dermatol ; 31(7): 986-992, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524394

RESUMO

Due to a steady increase in the number of individuals suffering from alopecia, this condition has recently received increasing attention. Alopecia can be caused by various pathological, environmental or psychological factors, eventually resulting in abnormalities in hair follicle (HF) structures or HF regeneration disorders, especially dysregulated hair follicle stem cell (HFSC) behaviour. HFSC behaviour includes activation, proliferation and differentiation. Appropriate HFSC behaviour sustains a persistent hair cycle (HC). HFSC behaviour is mainly influenced by HFSC metabolism, ageing and the microenvironment. In this review, we summarize recent findings on how HFSC metabolism, ageing and the microenvironment give rise to hair growth disorders, as well as related genes and signalling pathways. Recent research on the application of stem cell-based hair tissue engineering and regenerative medicine to treat alopecia is also summarized. Determining how dysregulated HFSC behaviour underlies alopecia would be helpful in identifying potential therapeutic targets.


Assuntos
Alopecia , Folículo Piloso , Alopecia/patologia , Diferenciação Celular/fisiologia , Cabelo , Folículo Piloso/fisiologia , Humanos , Células-Tronco
6.
PeerJ ; 10: e13033, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251789

RESUMO

BACKGROUND: People living with schizophrenia are at higher risk of disruptive behaviors, including violence, running away from home, and suicide attempts, which often co-occur and are highly correlated, yet seldom studied together. The current study investigated the frequency and correlates of disruptive behaviors among a Chinese community sample of individuals living with schizophrenia. METHODS: A cross-sectional study was conducted among 400 individuals living with schizophrenia from 12 communities. Data about disruptive behaviors in the past 2 months was collected using self-designed questionnaires. Clinical characteristics including psychiatric symptoms, depression, anxiety, disability, and functioning were collected by internationally standardized assessment instruments. RESULTS: About one-fifth (21%) of the subjects had experienced at least one form of disruptive behavior in the past 2 months. Violence was the most commonly reported (17.25%), which included damaging property (15%) and physical violence toward others (7.5%); followed by running away (6.5%), and suicide attempts (4%). Logistic regression analysis suggested that medication non-adherence (OR = 4.96, 95% CI [1.79-13.72]), involuntary hospital admission (OR = 5.35, 95% CI [2.06-13.87]), depression (OR = 2.34, 95% CI [1.07-5.10]), and lower social functioning (OR = 0.97, 95% CI [0.93-0.99]) were independently associated with a higher risk of disruptive behaviors. CONCLUSIONS: The overlap among three forms of disruptive behaviors warrants them to be assessed and studied together in clinical, research, and policy fields. The significant association between disruptive behaviors with medication non-adherence, involuntary admission, depression, and lower social functioning indicates the need for integrated, targeted, and needs-based intervention programs to be developed for the prevention and treatment of these disruptive behaviors.


Assuntos
Esquizofrenia , Tentativa de Suicídio , Humanos , Tentativa de Suicídio/psicologia , Esquizofrenia/epidemiologia , Prevalência , Estudos Transversais , Violência , China/epidemiologia
7.
J Invest Dermatol ; 142(9): 2476-2487.e9, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35148998

RESUMO

Melanoma is the leading cause of cutaneous malignancy death. BRAF inhibitors (BRAFis) have been developed as target therapies because nearly half of patients with melanoma have activating alterations in the BRAF oncogene. However, the fast-developed resistance to BRAFis limits their treatment efficacy. Understanding the molecular mechanism of resistance is vital to increase the success of clinical treatment. We searched three datasets (GSE42872, GSE52882, and GSE106321) from the Gene Expression Omnibus database, which analyzed the mRNA expression profile of melanoma cells under BRAFis treatment, and the differentially expressed genes were identified. Among all the differentially expressed genes, the increased expression of IRF9 and STAT2 was prominent and verified to be upregulated in BRAFis-treated melanoma cells. Furthermore, IRF9 or STAT2 overexpression led to less sensitivity, whereas IRF9 or STAT2 knockdown increased sensitivity to BRAFis treatment. In a subcutaneous xenograft tumor model, we showed that IRF9 or STAT2 overexpression slowed BRAFis-induced tumor shrinking, but IRF9 or STAT2 knockdown led to BRAFis-induced tumor shrinking more quickly. Interestingly, we discovered that IRF9-STAT2 signaling controlled GSDME-dependent pyroptosis by restoring GSDME transcription. These results suggest that targeting IRF9/STAT2 may lead to more promising effective treatments to prevent melanoma resistance to BRAFis by inducing pyroptosis.


Assuntos
Fator Gênico 3 Estimulado por Interferon, Subunidade gama , Melanoma , Proteínas Citotóxicas Formadoras de Poros , Piroptose , Fator de Transcrição STAT2 , Humanos , Fator Gênico 3 Estimulado por Interferon, Subunidade gama/metabolismo , Melanoma/tratamento farmacológico , Melanoma/genética , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Fator de Transcrição STAT2/genética , Transdução de Sinais
8.
Microsc Res Tech ; 85(1): 283-289, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34378833

RESUMO

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy that most commonly affects the apocrine glands of older men and women. Because it is associated with other cancers, early diagnosis and evaluation are needed. This study is to evaluate the value of reflectance confocal microscopy (RCM) in diagnosing EMPD. A total of 73 patients with clinically suspicious diagnosis of EMPD were enrolled in this study, and the RCM device imaged their lesions. Moreover, 67 patients underwent skin biopsies to confirm the diagnosis. We retrospectively analyzed the results of RCM and histological diagnosis and then evaluated the RCM value of biopsy-confirmed lesions. Based on the RCM image analysis, 54 of 73 (74.0%) patients were diagnosed with EMPD. Of all 67 biopsied lesions, 52 (77.6%) were EMPD. Then, we analyzed the RCM characteristics of 52 cases of biopsy-confirmed EMPD, compared their RCM image characteristics of three different lesions of EMPD, and further concluded the key points of EMPD under RCM microscopy based on the 52 EMPD cases. Finally, we focused on the differential diagnosis of EMPD from other skin diseases. RCM showed great diagnostic value in diagnosing EMPD.


Assuntos
Doença de Paget Extramamária , Neoplasias Cutâneas , Idoso , Biópsia , Feminino , Humanos , Masculino , Microscopia Confocal , Doença de Paget Extramamária/diagnóstico por imagem , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico por imagem
9.
Front Immunol ; 13: 1053558, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36713372

RESUMO

Background: Allergic rhinitis (AR) and chronic spontaneous urticaria (CSU) are often concurrent in patients. Changes in DNA methylation affect T cell biological processes, which may explain the occurrence and progression of comorbidity. However, downstream regulatory pathways of DNA methylation in two diseases and the underlying mechanisms have not been fully elucidated. Methods: The GSE50101, GSE72541, GSE50222 and OEP002482 were mined for the identification of differentially expressed genes (DEGs) or co-expressed genes and differentially methylated genes (DMGs) in AR and CSU patients. We applied GO analysis and consensus clustering to study the potential functions and signal pathways of selected genes in two diseases. GSVA and logistic regression analysis were used to find the regulatory pathway between DNA methylation and activation patterns of CD4+ T cells. Besides, we used the Illumina 850k chip to detect DNA methylation expression profiles and recognize the differentially methylated CpG positions (DMPs) on corresponding genes. Finally, we annotated the biological process of these genes using GO and KEGG pathway analysis. Result: The AR-related DEGs were found closely related to the differentiation and activation of CD4+ T cells. The DEGs or co-expressed genes of CD4+ T cells in AR and CSU patients were also clustered using GO and KEGG analysis and we got 57 co-regulatory pathways. Furthermore, logistic regression analysis showed that the regulation of cellular component size was closely related to the activation of CD4+ T cells regulated by DNA methylation. We got self-tested data using the Illumina 850k chip and identified 98 CpGs that were differentially methylated in patients. Finally, we mapped the DMPs to 15 genes and found that they were mainly enriched in the same CD4+T cell regulating pathway. Conclusion: Our study indicated that DNA methylation affected by pollen participated in the activation patterns of CD4 + T cells, providing a novel direction for the symptomatic treatment of the co-occurrence of AR and CSU.


Assuntos
Metilação de DNA , Rinite Alérgica , Humanos , Rinite Alérgica/genética , Rinite Alérgica/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Transdução de Sinais/genética
10.
BMC Med Educ ; 21(1): 606, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34879860

RESUMO

BACKGROUND: In this study, we applied the small private online course (SPOC) and team-based learning (TBL) blended teaching model to dermatology and venereology to ensure a higher quality learning experience for clinical medical students. METHODS: A total of 52 fifth-grade clinical undergraduates from Xiangya School of Medicine of Central South University were randomly divided into an experimental (n = 26) and a control group (n = 26). In March 2018, we used the SPOC and TBL blended teaching model in the experimental group and explored the effects of innovative teaching in the dermatology and venereology course, compared with the control group receiving the conventional teaching method. We analyzed the two groups' theoretical assessment scores and questionnaire results to evaluate the efficiency of the new pedagogy. RESULTS: Students in the experimental group had a better understanding than the control group of the dermatology and venereology content and higher scores on the case analysis questions in the final theoretical examination. The results revealed that the majority of the experimental group students agreed that the novel teaching model blended with SPOC&TBL helped them significantly stimulate motivation and develop their ability in self-directed learning, independent thinking, literature retrieval, presentation board, teamwork, communication, and systematic clinical thinking. The teaching satisfaction survey of the two groups showed that the students' satisfaction in the experimental group was significantly higher than in the control group (p < 0.05). CONCLUSIONS: The SPOC&TBL teaching model is better than the traditional one in enriching students' professional knowledge and cultivating their comprehensive ability. It can effectively promote educational quality, improve students' learning effects, and enhance their satisfaction. This method has broad application prospects.


Assuntos
Dermatologia , Estudantes de Medicina , Venereologia , Avaliação Educacional , Humanos , Aprendizagem Baseada em Problemas , Ensino
11.
Drug Des Devel Ther ; 15: 3255-3276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349502

RESUMO

BACKGROUND: Huai Hua San (HHS), a famous Traditional Chinese Medicine (TCM) formula, has been widely applied in treating ulcerative colitis (UC). However, the interaction of bioactives from HHS with the targets involved in UC has not been elucidated yet. AIM: A network pharmacology-based approach combined with molecular docking and in vitro validation was performed to determine the bioactives, key targets, and potential pharmacological mechanism of HHS against UC. MATERIALS AND METHODS: Bioactives and potential targets of HHS, as well as UC-related targets, were retrieved from public databases. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis, including protein-protein interaction (PPI), as well as the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Subsequently, molecular docking was carried out to predict the combination of active compounds with core targets. Lastly, in vitro experiments were conducted to further verify the findings. RESULTS: A total of 28 bioactive ingredients of HHS and 421 HHS-UC-related targets were screened. Bioinformatics analysis revealed that quercetin, luteolin, and nobiletin may be potential candidate agents. JUN, TP53, and ESR1 could become potential therapeutic targets. PI3K-AKT signaling pathway might play an important role in HHS against UC. Moreover, molecular docking suggested that quercetin, luteolin, and nobiletin combined well with JUN, TP53, and ESR1, respectively. Cell experiments showed that the most important ingredient of HHS, quercetin, could inhibit the levels of inflammatory factors and phosphorylated c-Jun, as well as PI3K-Akt signaling pathway in LPS-induced RAW264.7 cells, which further confirmed the prediction by network pharmacology strategy and molecular docking. CONCLUSION: Our results comprehensively illustrated the bioactives, potential targets, and molecular mechanism of HHS against UC. It also provided a promising strategy to uncover the scientific basis and therapeutic mechanism of TCM formulae in treating diseases.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede , Animais , Camundongos , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Quercetina/farmacologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
12.
Front Immunol ; 12: 699900, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220863

RESUMO

Background: Keratinocytes of psoriasis have anti-apoptotic properties including delayed apoptosis process, accelerated proliferation metabolism and postponed differentiation process. However, the specific mechanism leading to the abnormal biological behavior of keratinocytes remains unclear. Objectives: We investigated the role of increased RPL22 expression in regulating the abnormal biological behavior of keratinocytes and the mechanism of regulation of RPL22 expression in skin lesions of psoriatic patients. Methods: We examined clinical samples and utilized cytokine-induced cell and IMQ-treated mouse models. We determined the expression and functions of RPL22 in vitro and in vivo. Results: We showed that RPL22 expression was significantly increased in the skin lesions of psoriasis patients and IMQ-treated psoriatic-like mice. Such increased expression is attributed to hyperacetylation of histone H3K27 in the promoter region of RPL22. Interestingly, overexpression of RPL22 enhanced keratinocyte proliferation by increasing cyclinD1 expression and accelerated CD4+T cells recruitment via upregulating CXCL10 expression. Finally, we demonstrated that RPL22 overexpression promoted psoriasiform phenotypes in IMQ-induced mouse skins. Conclusions: These findings suggested that RPL22 regulates keratinocytes abnormal biological behavior and contributes to the development of psoriatic phenotypes. Thus, RPL22 might be a novel potential molecular target for treatment of psoriasis.


Assuntos
Queratinócitos/metabolismo , Queratinócitos/patologia , Psoríase/metabolismo , Psoríase/patologia , Proteínas de Ligação a RNA/metabolismo , Proteínas Ribossômicas/metabolismo , Animais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Regulação para Cima
13.
Photodiagnosis Photodyn Ther ; 35: 102356, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34048971

RESUMO

BACKGROUND: Different therapies such as clindamycin, rifampicin, isotretinoin, or corticosteroids have been used for folliculitis decalvans with poor results. Recently, PDT has been used for treating folliculitis decalvans more frequently. However, the efficacy of PDT for treating folliculitis decalvans is lacking consensus. In this study, we conducted a retrospective analysis to evaluated the status of PDT for the treatment of folliculitis decalvans. METHODS: 13 cases of folliculitis decalvans patients were treated with ALA-PDT. The treatment totals 3 times, and the interval between each treatment was 10-14 days. A follow-up was conducted at 12 months after the last treatment. The condition was graded according to the following evaluation criteria: recovery, significant improvement, moderate improvement, ineffective. RESULTS: A total of 7 cases improved significantly, and 6 cases improved moderately followed the first treatment. After the second treatment, 10 cases showed significant improvement, and 2 cases responded poorer than the first treatment. After the third treatment, 4 cases recovered, 7 cases improved significantly, and 2 case moderately improved. At the 12-months follow-up, 9 out of 13 patients were well controlled and with no recurrence. The other 4 patients relapsed. CONCLUSION: In summary, photodynamic therapy shows overall favorable effect on folliculitis decalvans and should be considered as a method for the treatment of folliculitis decalvans.


Assuntos
Foliculite , Fotoquimioterapia , Alopecia , Foliculite/tratamento farmacológico , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos
14.
Exp Dermatol ; 30(11): 1588-1597, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33963624

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory skin disease involving skin barrier dysfunction and immune imbalance. However, the mechanism of AD is not clear completely and may be related to heredity and environment. Neuropeptides are a class of peptides secreted by nerve endings, they may play roles in promoting vasodilation, plasma extravasation, chemotaxis of inflammatory cells and mediating pruritus. Since itching and immune cell infiltration are the main manifestations of atopic dermatitis, to further investigate the impact of neuropeptides on AD, our review summarized the mechanisms of several common neuropeptides in AD and hypothesized that neuropeptides may be the novel potential targets in AD treatment.


Assuntos
Dermatite Atópica/etiologia , Neuropeptídeos/fisiologia , Humanos
15.
Ageing Res Rev ; 69: 101349, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33984527

RESUMO

Melanogenesis is a complex process in which melanin is synthesized in melanocytes and transported to keratinocytes, which involves multiple genes and signaling pathways. Epigenetics refers to the potential genetic changes that affect gene expression without involving changes in the original sequence of DNA nucleotides. DNA methylation regulates the expression of key genes such as tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), dopachrome tautomerase (DCT) and microphthalmia-associated transcription factor (MITF), as well as paracrine factors such as stem cell factor (SCF) and endothelin-1 (ET-1) in melanogenesis. Potential DNA methylation sites are present in the genes of melanogenesis-related signaling pathways such as "Wnt", "PI3K/Akt/CREB" and "MAPK". H3K27 acetylation is abundant in melanogenesis-related genes. Both the upstream activation and downstream regulation of MITF depend on histone acetyltransferase CBP/p300, and pH-induced H3K27 acetylation may be the amplifying mechanism of MITF's effect. HDAC1 and HDAC10 catalyze histone deacetylation of melanogenesis-related gene promoters. Chromatin remodelers SWI/SNF complex and ISWI complex use the energy of ATP hydrolysis to rearrange nucleosomes, while their active subunits BRG1, BRM and BPTF, act as activators and cofactors of MITF. MicroRNAs (miRNAs) can directly target a large number of melanogenesis-related genes, while long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) regulate melanogenesis in a variety of ways. Interactions exist among the epigenetic mechanisms of melanogenesis. For example, the methyl CpG binding domain protein 2 (MeCP2) links DNA methylation, histone deacetylation, and histone methylation. Epigenetic-based therapy provides novel opportunities for treating dermatoses that are caused by pigmentation disturbances. This review summarizes the epigenetic regulation mechanisms of melanogenesis, and examines the pathogenesis and treatment of epigenetics in pigmentation disorders.


Assuntos
Epigênese Genética , Melaninas , Melanócitos , Animais , Regulação da Expressão Gênica , Humanos , Melaninas/metabolismo , Melanócitos/metabolismo
16.
Skin Res Technol ; 27(5): 871-879, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33847402

RESUMO

BACKGROUND: Actinic keratosis (AK) occurs frequently in sun-exposed skin while its diagnosis and treatment were still in exploration. MATERIALS AND METHODS: Thirty two patients with facial AK lesions were selected and examined with reflective confocal microscopy (RCM) firstly, followed by biopsy at the same site. RCM was used to observe AK lesions before 5-aminolevulinic acid photodynamic therapy (ALA-PDT) treatment, after the first treatment, after 4 treatments, and at 1 and 6 months follow-up. Retrospective analysis of RCM images was performed. RESULTS: Thirty two AK cases showed initial RCM microscopic features including disorderly arranged epidermal cells (100%), atypical keratinocytes (100%), and blurry border between the epidermis and dermis (100%). 4 patients quitted trail. After treatments, 24 cases showed basically regular arrangement of epidermal cells, absent atypical keratinocytes, and clear border between epidermis and dermis, while 4 cases improved little. At 1 and 6 months follow-up, 23 cases remained relapse-free while 1 case developed recurrent symptoms. Effective rate of 4 ALA-PDT treatments for AK was 100%; recurrence and cure rates were 4.2% and 82.1%, respectively. CONCLUSION: ALA-PDT is effective to treat AK, while RCM can be recommended for in vivo evaluating and monitoring the effect of ALA-PDT on AK.


Assuntos
Ceratose Actínica , Fotoquimioterapia , Ácido Aminolevulínico/uso terapêutico , Humanos , Ceratose Actínica/diagnóstico por imagem , Ceratose Actínica/tratamento farmacológico , Microscopia Confocal , Recidiva Local de Neoplasia , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
17.
Int J Biol Sci ; 17(3): 712-727, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33767583

RESUMO

Tight junction (TJ) is a "zippering up" junction structure located at the uppermost portion of adjacent epithelial/endothelial cells in organs and tissues. TJs maintain the relative stability of intracellular substances and functions by closing or opening intercellular pathways, coordinating the entry and exit of molecules of different sizes and charges, and regulating the permeability of paracellular barrier. TJs also prevent microbial invasion, maintain epithelial/endothelial cell polarity, and regulate cell proliferation. TJs are widely present in the skin and mucosal epithelial barriers, intestinal epithelial barrier, glomerular filtration barrier, bladder epithelial barrier, blood-brain barrier, brain-blood tumor barrier, and blood-testis barrier. TJ dysfunction in different organs can lead to a variety of diseases. In addition to signal pathways, transcription factors, DNA methylation, histone modification, TJ proteins can also be regulated by a variety of non-coding RNAs, such as micro-RNAs, long-noncoding RNAs, and circular RNAs, directly or indirectly. This review summarizes the structure of TJs and introduces the functions and regulatory mechanisms of TJs in different organs and tissues. The roles and mechanisms of non-coding RNAs in the regulation of TJs are also highlighted in this review.


Assuntos
RNA não Traduzido/fisiologia , Proteínas de Junções Íntimas/fisiologia , Junções Íntimas/fisiologia , Citoesqueleto de Actina/fisiologia , Animais , Barreira Hematoencefálica , Barreira Hematotesticular , Humanos , Mucosa Intestinal/fisiologia
18.
Front Immunol ; 12: 630112, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33643314

RESUMO

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease characterized by continuous inflammation and the production of autoantibodies. Exosomes, acting as a critical tool for communication between cells, are involved in the pathogenesis of SLE, particularly in inflammation and immune imbalance. In this study, we aimed to extract and confirm the pro-inflammatory effect of serum exosomes in SLE. Then, we attempted to find differentially expressed exosomal microRNAs in the serum of healthy subjects and SLE patients via miRNA microarray analysis and validated the target exosomal microRNA, exosomal miR-451a, which expression level decreased in serum of SLE patients by RT-qPCR. Furtherly, we analyzed the correlation between exosomal miR-451a and disease activity, kidney damage and typing, and traditional medicine therapy. Finally, we investigated the intercellular communication role of exosomal miR-451a in SLE by co-culture assay in vitro. Taken together, our study demonstrated that downregulated serum exosomal miR-451a expression correlated with SLE disease activity and renal damage as well as its intercellular communication role in SLE which provided potential therapeutic strategies.


Assuntos
Comunicação Celular , Exossomos/fisiologia , Rim/patologia , Lúpus Eritematoso Sistêmico/etiologia , MicroRNAs/fisiologia , Adulto , Regulação para Baixo , Exossomos/química , Feminino , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/classificação , Masculino , MicroRNAs/sangue , Adulto Jovem
19.
Photodermatol Photoimmunol Photomed ; 37(5): 442-448, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33738849

RESUMO

Programmed cell death (PCD) is a basic component of life and an important terminal path for cells. A variety of biological events are associated with PCD, including the conservation of tissue homeostasis and removal of harmful cells. Overexposure of the skin to UV radiation causes skin photodamage. Keratinocytes are the first line of defence against ultraviolet radiation. During UV radiation, the keratinocyte can undergo four modes of PCD: apoptosis, pyroptosis, necroptosis and autophagy. The molecular mechanisms of these four modes of PCD have been widely studied as potential therapeutic targets for the prevention of UV-induced skin inflammation, ageing and skin cancer. In this review, we summarize the role of keratinocyte PCD in the pathogenesis of UV-induced skin photodamage. This article will provide new research directions for the design of intervention strategies for the treatment and prevention of skin photodamage.


Assuntos
Apoptose , Raios Ultravioleta , Autofagia , Queratinócitos , Pele , Raios Ultravioleta/efeitos adversos
20.
Dermatol Ther ; 34(2): e14844, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33528092

RESUMO

This study investigated the mechanism and efficacy of topical acidified aliphatic ester for treatment of axillary osmidrosis (AO). A total of 32 AO patients were enrolled in this study. In the initial pilot study, 20 patients were double-blindly, randomly divided into acidified aliphatic ester or aliphatic ester treatment groups, followed by efficacy evaluation after 4 weeks. Then, all patients (n = 32) were treated with topical acidified aliphatic ester for 16 weeks. Efficacy was evaluated at every 4 weeks, and at 3- and 6-month follow-ups. Changes of pH values and microecology at targeting sites were analyzed. In the first cohort (n = 20) of pilot study, acidified aliphatic ester showed significantly higher curative rate (60% vs 10%, P < .05) and effective rate (90% vs 30%; P < .05) than aliphatic ester. For the next 16 weeks, 25 of 32 cases completed treatment. Curative rate showed gradual and significant increases from 64% to 96% during the treatment courses (P = .001); it slightly but insignificantly decreased at 3- and 6- month follow-ups. Abundance of Corynebacterium and Anaerobic bacteria decreased while Staphylococcus increased after treatments. Axillary pH values negatively correlated with Staphylococcus abundance (r = -.40, P = .01) and positively with Corynebacterium abundance (r = .64, P = .01). We concluded that topical acidified aliphatic ester could effectively alleviate conditions of AO patients by reducing value of axillary pH and rebalancing axillary microecology.


Assuntos
Hiperidrose , Doenças das Glândulas Sudoríparas , Axila , Ésteres , Humanos , Projetos Piloto
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