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1.
Dermatology ; 238(5): 837-845, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35078198

RESUMO

BACKGROUND: The inflammatory lesions of acne leave scars which greatly affect patients' quality of life. Treatment options targeting both acne and acne scars are still lacking. OBJECTIVES: To evaluate the clinical efficacy of epidermal growth factor ointment (EGFO) on acne and acne scars. METHODS: The study design was 12-week, prospective, split-face, single-blinded. The 36 patients with mild to moderate acne vulgaris applied EGFO on one side of the face and the vehicle ointment on the other side twice daily. The patients were assessed every 4 weeks by acne lesion and scar counts, investigator's global assessment for acne (IGA) and scar (SGA), and the ECCA scar grading scale. Biopsies were performed before and after treatment. RESULTS: Acne and acne scars were significantly improved on EGFO-treated sides, while control sides were not. Acne lesion and scar counts were significantly reduced after 4 weeks, while IGA, SGA, and ECCA grade significantly decreased after 8 weeks. Immunohistochemistry showed decreased expression of keratin 16, NF-κB p65, IL-1α, and IL-8, and increased expression of TGF-ß1, elastin, and collagen type 1, 3 after treatment. CONCLUSIONS: EGFO can be a treatment option targeting acne and acne scars.


Assuntos
Acne Vulgar , Cicatriz , Acne Vulgar/complicações , Acne Vulgar/tratamento farmacológico , Acne Vulgar/patologia , Cicatriz/tratamento farmacológico , Cicatriz/etiologia , Cicatriz/patologia , Fator de Crescimento Epidérmico/uso terapêutico , Humanos , Imunoglobulina A/uso terapêutico , Pomadas/uso terapêutico , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento
2.
Dermatology ; 237(6): 907-911, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33091912

RESUMO

BACKGROUND: Granulomatous rosacea (GR) is a rare inflammatory skin disease, which is considered a variant of rosacea, apart from other types of rosacea. OBJECTIVE: This study aimed to summarize the characteristics of Korean patients diagnosed with GR by combining clinical and histological findings. METHODS: Fifteen cases, both clinically and histologically consistent with GR, were selected and were subsequently analyzed to describe clinical and histological characteristics. RESULTS: A total of 20 patients showed granulomatous infiltration in skin biopsies, but only 15 of them were clinically consistent with GR. Five patients who showed granulomatous inflammation were clinically consistent with erythematotelangiectatic or papulopustular rosacea. Among 15 patients, 13 (86.7%) were female and 2 (13.3%) were male. The most frequently involved area was the cheek, and none of the patients showed extrafacial lesions. There seems to be a possibility that treatment duration may be associated with the treatment response. CONCLUSIONS: This study confirms clinical characteristics of GR based on the diagnosis combining both clinical and histological findings.


Assuntos
Povo Asiático , Rosácea/patologia , Adulto , Antibacterianos/uso terapêutico , Estudos de Coortes , Fármacos Dermatológicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Rosácea/complicações , Rosácea/terapia
3.
J Korean Med Sci ; 31(1): 114-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26770046

RESUMO

We aimed to validate the Inventory of Complicated Grief (ICG)-Korean version among 1,138 Korean adolescents, representing a response rate of 57% of 1,997 students. Participants completed a set of questionnaires including demographic variables (age, sex, years of education, experience of grief), the ICG, the Children's Depression Inventory (CDI) and the Lifetime Incidence of Traumatic Events-Child (LITE-C). Exploratory factor analysis was performed to determine whether the ICG items indicated complicated grief in Korean adolescents. The internal consistency of the ICG-Korean version was Cronbach's α=0.87. The test-retest reliability for a randomly selected sample of 314 participants in 2 weeks was r=0.75 (P<0.001). Concurrent validity was assessed using a correlation between the ICG total scores and the CDI total scores (r=0.75, P<0.001). The criterion-related validity based on the comparison of ICG total scores between adolescents without complicated grief (1.2 ± 3.7) and adolescent with complicated grief (3.2 ± 6.6) groups was relatively high (t=5.71, P<0.001). The data acquired from the 1,138 students was acceptable for a factor analysis (Kaiser-Meyer-Olkin Measure of Sampling Adequacy=0.911; Bartlett's Test of Sphericity, χ(2)=13,144.7, P<0.001). After omission of 3 items, the value of Cronbach's α increased from 0.87 for the 19-item ICG-Korean version to 0.93 for the 16-item ICG-Korean version. These results suggest that the ICG is a useful tool in assessing for complicated grief in Korean adolescents. However, the 16-item version of the ICG appeared to be more valid compared to the 19-item version of the ICG. We suggest that the 16-item version of the ICG be used to screen for complicated grief in Korean adolescents.


Assuntos
Pesar , Psicometria/métodos , Adolescente , Criança , Análise Fatorial , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , República da Coreia , Inquéritos e Questionários
5.
Cancers (Basel) ; 16(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38893126

RESUMO

PURPOSE: Papillary renal cell carcinoma (PRCC), the second most common kidney cancer, is morphologically, genetically, and molecularly heterogeneous with diverse clinical manifestations. Genetic variations of PRCC and their association with survival are not yet well-understood. This study aimed to identify and validate survival-specific genes in PRCC and explore their clinical utility. MATERIALS AND METHODS: Using machine learning, 293 patients from the Cancer Genome Atlas-Kidney Renal Papillary Cell Carcinoma (TCGA-KIRP) database were analyzed to derive genes associated with survival. To validate these genes, DNAs were extracted from the tissues of 60 Korean PRCC patients. Next generation sequencing was conducted using a customized PRCC gene panel of 202 genes, including 171 survival-specific genes. Kaplan-Meier and Log-rank tests were used for survival analysis. Fisher's exact test was performed to assess the clinical utility of variant genes. RESULTS: A total of 40 survival-specific genes were identified in the TCGA-KIRP database through machine learning and statistical analysis. Of them, 10 (BAP1, BRAF, CFDP1, EGFR, ITM2B, JAK1, NODAL, PCSK2, SPATA13, and SYT5) were validated in the Korean-KIRP database. Among these survival gene signatures, three genes (BAP1, PCSK2, and SPATA13) showed survival specificity in both overall survival (OS) (p = 0.00004, p = 1.38 × 10-7, and p = 0.026, respectively) and disease-free survival (DFS) (p = 0.00002, p = 1.21 × 10-7, and p = 0.036, respectively). Notably, the PCSK2 mutation demonstrated survival specificity uniquely in both the TCGA-KIRP (OS: p = 0.010 and DFS: p = 0.301) and Korean-KIRP (OS: p = 1.38 × 10-7 and DFS: p = 1.21 × 10-7) databases. CONCLUSIONS: We discovered and verified genes specific for the survival of PRCC patients in the TCGA-KIRP and Korean-KIRP databases. The survival gene signature, including PCSK2 commonly obtained from the 40 gene signature of TCGA and the 10 gene signature of the Korean database, is expected to provide insight into predicting the survival of PRCC patients and developing new treatment.

6.
J Endocr Soc ; 8(7): bvae093, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38799767

RESUMO

Context: Paragangliomas (PGLs) are rare tumors in adrenal and extra-adrenal locations. Metastasis are found in approximately 5% to 35% of PGLs, and there are no reliable predictors of metastatic disease. Objective: This work aimed to develop a prognostic score of metastatic potential in PGLs. Methods: A retrospective analysis was conducted of clinical data from a cohort with PGLs and tumor histological assessment. Patients were divided into metastatic PGL (presence of metastasis) and nonmetastatic PGL (absence of metastasis ≥96 months of follow-up) groups. Univariate and multivariable analysis were performed to identify predictors of metastatic potential. A prognostic score was developed based on coefficients of multivariable analysis. Kaplan-Meier curves were generated to estimate disease-specific survival (DSS). Results: Out of 263 patients, 35 patients had metastatic PGL and 110 patients had nonmetastatic PGL. In multivariable analysis, 4 features were independently related to metastatic disease and composed the Prognostic Score of Paragangliomas (PSPGL): presence of central or confluent necrosis (33 points), more than 3 mitosis/10 high-power field (HPF) (28 points), extension into adipose tissue (20 points), and extra-adrenal location (19 points). A PSPGL of 24 or greater showed similar sensitivity with higher specificity than the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP). PSPGL less than or equal to 20 was associated with a risk of metastasis of approximately 10%, whereas a PSPGL of 40 or greater was associated with approximately 80%. The presence of metastasis and Ki-67 of 3% or greater were related to lower DSS. Conclusion: The PSPGL, composed of 4 easy-to-assess parameters, demonstrated good performance in predicting metastatic potential and good ability in estimating metastasis risk.

7.
J Gen Virol ; 94(Pt 8): 1712-1722, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23636824

RESUMO

Influenza virus infects host cells through membrane fusion, a process mediated by the low pH-induced conformational change of the viral surface glycoprotein haemagglutinin (HA). We determined the structures and biochemical properties of the HA proteins from A/Korea/01/2009 (KR01), a 2009 pandemic strain, and A/Thailand/CU44/2006 (CU44), a seasonal strain. The crystal structure of KR01 HA revealed a V-shaped head-to-head arrangement, which is not seen in other HA proteins including CU44 HA. We isolated a broadly neutralizing H1-specific monoclonal antibody GC0757. The KR01 HA-Fab0757 complex structure also exhibited a head-to-head arrangement of HA. Both native and Fab complex structures reveal a different spatial orientation of HA1 relative to HA2, indicating that HA is flexible and dynamic at neutral pH. Further, the KR01 HA exhibited significantly lower protein stability and increased susceptibility to proteolytic cleavage compared with other HAs. Our structures provide important insights into the conformational flexibility of HA.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Orthomyxoviridae/química , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/isolamento & purificação , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , Cristalografia por Raios X , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Modelos Moleculares , Orthomyxoviridae/imunologia , Conformação Proteica , Estabilidade Proteica , Proteólise
8.
Mol Cancer Ther ; 22(3): 333-342, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36808277

RESUMO

PARP inhibitors have been approved by the FDA for use in the treatment of patients with ovarian, breast, pancreatic, and prostate cancers. PARP inhibitors show diverse suppressive effects on PARP family members and PARP-DNA trapping potency. These properties are associated with distinct safety/efficacy profiles. Here, we report the nonclinical characteristics of venadaparib (also known as IDX-1197 or NOV140101), a novel potent PARP inhibitor. The physiochemical properties of venadaparib were analyzed. Furthermore, the efficacy of venadaparib against PARP enzymes, PAR formation, and PARP trapping activities, and growth inhibition of cell lines with BRCA mutations were evaluated. Ex vivo and in vivo models were also established to study pharmacokinetics/pharmacodynamics, efficacy, and toxicity. Venadaparib specifically inhibits PARP-1 and -2 enzymes. Oral administration of venadaparib HCl at doses above 12.5 mg/kg significantly reduced tumor growth in the OV_065 patient-derived xenograft model. Intratumoral PARP inhibition remained at over 90% until 24 hours after dosing. Venadaparib had wider safety margins than olaparib. Notably, venadaparib showed favorable physicochemical properties and superior anticancer effects in homologous recombination-deficient in vitro and in vivo models with improved safety profiles. Our results suggest the possibility of venadaparib as a next-generation PARP inhibitor. On the basis of these findings, phase Ib/IIa studies on the efficacy and safety of venadaparib have been initiated.


Assuntos
Antineoplásicos , Inibidores de Poli(ADP-Ribose) Polimerases , Masculino , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Recombinação Homóloga
9.
Lab Invest ; 91(8): 1229-40, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21519328

RESUMO

The transplantation of adult stem cells into recipients is a method used widely in mammals to determine the fate of transferred cells, and for the production of progenies. This study is the first report, to our knowledge, to demonstrate the successful production of chickens using cells transdifferentiated from adult chicken bone marrow cells (BMCs) transplanted into the testes. BMCs from the enhanced green fluorescent protein (eGFP) transgenic (Tg) chickens were induced via in vitro transdifferentiation to male germ cells and injected into the testes of normal recipients. The multipotency of BMC was found with RT-PCR, immunocytochemistry, and FACS using specific markers, such as OCT4 and SSEA-1, -3, and -4. Localization and in vivo transdifferentiation of injected cells in the seminiferous tubules of recipients were traced for up to 40 days' post-injection by GFP expression and immunocytochemical analyses. The integration of the eGFP and the neo(R) genes in sperm gDNAs of recipient was confirmed via PCR analysis. A subsequent testcross of the recipient roosters with non-Tg hens resulted in the production of eGFP Tg progenies, demonstrating the successful transdifferentiation of the adult BMC to the germ cells in the testis. Therefore, we suggest that the use of adult BMCs is a new and promising approach to the production of Tg poultry, and may prove helpful in the study of avian developmental biology.


Assuntos
Animais Geneticamente Modificados , Células da Medula Óssea/fisiologia , Transdiferenciação Celular , Galinhas/genética , Espermatozoides/citologia , Células-Tronco Adultas/fisiologia , Animais , Engenharia Genética , Masculino
10.
J Dermatol ; 48(1): 42-48, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33180351

RESUMO

Various evaluation methods for acne severity have been used without standardization, and the diversity of acne outcome measures is an obstacle to the integrated analysis of various acne studies. In this study, we sought to investigate physician-based evaluation methods used in clinical studies of acne vulgaris and to determine differences according to time, region and study design. PubMed was searched for articles on acne published from January 2000 to June 2019 in five dermatology journals: Journal of the American Academy of Dermatology, JAMA Dermatology, British Journal of Dermatology, Journal of the European Academy of Dermatology and Venereology and Acta Dermato-Venereologica. A total of 186 articles with acne evaluation methods were selected. Among the selected studies, region, study design, type of intervention and the number of subjects were identified and analyzed. Articles from 2010 to 2019 used Investigator Global Assessment (IGA; odds ratio [OR], 5.808; 95% CI, 1.894-17.811) more often and the Leeds technique (OR, 0.282; 95% CI, 0.098-0.812) less often compared with articles from 2000 to 2009. Controlled experimental studies preferred lesion counting (OR, 238.637; 95% CI, 46.795-1216.954), IGA (OR, 9.177; 95% CI, 3.053-27.586) and Leeds Revised Acne Grading System (LRAGS; OR, 10.844; 95% CI, 3.050-38.559) compared with observational studies. North American studies applied lesion counting (OR, 4.573; 95% CI, 1.173-17.836) and IGA (OR, 11.330; 95% CI, 3.487-36.818) more often and LRAGS (OR, 0.171; 95% CI, 0.039-0.758) less often compared with European studies. This study demonstrated the diversity and heterogeneity of acne outcome measures even in highly influential dermatology journals. This is due to the limitations of current methods and suggests the importance of developing a core outcome measure.


Assuntos
Acne Vulgar , Médicos , Acne Vulgar/diagnóstico , Acne Vulgar/terapia , Humanos
11.
J Dermatolog Treat ; 32(3): 297-301, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-31424962

RESUMO

BACKGROUND: Herbal extracts with fewer adverse effects can be an alternative to these drugs because they can target various molecular pathways of acne pathogenesis. OBJECTIVES: To evaluate the clinical efficacy of herbal extracts (mangosteen, Lithospermum officinale, Tribulus terrestris L., Houttuynia cordata Thunb) for the treatment of mild to moderate acne vulgaris. METHODS: Sixty patients were randomized in a 1:1 ratio to receive blinded treatment with herbal extracts or vehicle for 8 weeks. Inflammatory and non-inflammatory acne lesion counts, Investigator's Global Assessment, patient's satisfaction and safety profiles were assessed. We also performed skin biopsy at baseline and week 8 to confirm immunological changes with immunohistochemistry staining. RESULTS: By the end of the study period, both inflammatory and non-inflammatory acne lesion counts were significantly decreased in herbal extracts group (p< .05). In immunohistochemistry staining, expressions of IL-1α, IL-8, and keratin 16 were significantly decreased in herbal extracts group compared to vehicle group from baseline to week 8. There was no serious adverse events in both groups. CONCLUSIONS: This herbal extracts can be a new therapeutic option for patients with mild to moderate acne vulgaris who are reluctant to use drugs.


Assuntos
Acne Vulgar/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Acne Vulgar/patologia , Administração Cutânea , Adulto , Método Duplo-Cego , Esquema de Medicação , Feminino , Garcinia mangostana/química , Garcinia mangostana/metabolismo , Humanos , Interleucina-1alfa/metabolismo , Lithospermum/química , Lithospermum/metabolismo , Masculino , Satisfação do Paciente , Extratos Vegetais/química , Índice de Gravidade de Doença , Pele/metabolismo , Pele/patologia , Resultado do Tratamento , Adulto Jovem
12.
Biochem Biophys Res Commun ; 397(4): 679-84, 2010 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-20594970

RESUMO

A major problem in the treatment of type 1 diabetes mellitus is the limited availability of alternative sources of insulin-producing cells for islet transplantation. In this study, we investigated the effect of bone morphogenetic protein 4 (BMP-4) treatments of gnotobiotic porcine skin-derived stem cells (gSDSCs) on their reprogramming and subsequent differentiation into insulin-producing cells (IPCs). We isolated SDSCs from the ear skin of a gnotobiotic pig. During the proliferation period, the cells expressed stem-cell markers Oct-4, Sox-2, and CD90; nestin expression also increased significantly. The cells could differentiate into IPCs after treatments with activin-A, glucagon-like peptide-1 (GLP-1), and nicotinamide. After 15days in the differentiation medium, controlled gSDSCs began expressing endocrine progenitor genes and proteins (Ngn3, Neuro-D, PDX-1, NKX2.2, NKX6.1, and insulin). The IPCs showed increased insulin synthesis after glucose stimulation. The results indicate that stem cells derived from the skin of gnotobiotic pigs can differentiate into IPCs under the appropriate conditions in vitro. Our three-stage induction protocol could be applied without genetic modification to source IPCs from stem cells in the skin of patients with diabetes for autologous transplantation.


Assuntos
Proteína Morfogenética Óssea 4/farmacologia , Vida Livre de Germes , Células Secretoras de Insulina/fisiologia , Pele/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Engenharia Tecidual/métodos , Animais , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Células Cultivadas , Reprogramação Celular , Diabetes Mellitus Tipo 1/terapia , Expressão Gênica , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/citologia , Transplante das Ilhotas Pancreáticas , Pele/citologia , Células-Tronco/citologia , Suínos
13.
J Cosmet Dermatol ; 19(4): 891-895, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31347777

RESUMO

BACKGROUNDS: We previously reported the efficacy of 0.1% 4-n-butylresorcinol (4nBR) cream in the treatment melasma and synergistic effect of 4nBR and resveratrol (RSV) to inhibit melanogenesis in vitro. AIMS: To evaluate efficacy and safety of a cream which contains liposome-encapsulated 4nBR and RSV in the treatment of melasma. PATIENTS/METHODS: A total of 21 female patients with melasma were treated with the cream for 4 weeks. At baseline, week 2, and week 4, melanin index (MI) of the lesional and preauricular nonlesional skin was measured and two blinded, independent dermatologists assessed the overall severity by 5-point scale. RESULTS: The lesional MI was significantly decreased at weeks 2 and 4 compared with the baseline while no significant change in the nonlesional MI was observed throughout the study. The mean investigator's global assessment score was also significantly improved at weeks 2 and 4. In patient's self-assessment, 8 (38.1%) and 11 (52.3%) patients answered moderate to significant improvement in their melasma at weeks 2 and 4, respectively. No serious adverse events were reported. CONCLUSION: The cream containing liposome-encapsulated 4nBR and RSV was shown to be effective and safe for the treatment of melasma with its effect appearing as early as 2 weeks.


Assuntos
Cosmecêuticos/administração & dosagem , Melanose/tratamento farmacológico , Resorcinóis/administração & dosagem , Resveratrol/administração & dosagem , Adulto , Cosmecêuticos/efeitos adversos , Cosmecêuticos/química , Cosmecêuticos/farmacocinética , Sinergismo Farmacológico , Feminino , Humanos , Lipossomos , Masculino , Melaninas/biossíntese , Melanose/diagnóstico , Pessoa de Meia-Idade , Fotografação , Resorcinóis/efeitos adversos , Resorcinóis/farmacocinética , Resveratrol/efeitos adversos , Resveratrol/farmacocinética , Índice de Gravidade de Doença , Pele/diagnóstico por imagem , Pele/efeitos dos fármacos , Pele/metabolismo , Creme para a Pele/administração & dosagem , Creme para a Pele/efeitos adversos , Creme para a Pele/química , Creme para a Pele/farmacocinética , Resultado do Tratamento
14.
Ann Dermatol ; 31(6): 662-665, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33911666

RESUMO

Hair follicle nevus (HFN) is a rare, benign, follicular hamartoma that most frequently presents as a congenital nodule on the face. We experienced a rare case of HFN on the neck of a 14-year-old boy and performed a pilot immunohistochemical study with cytokeratin 19 (CK19) to compare the staining pattern of hair follicles in HFN and its differential diagnoses, accessory tragus, cervical chondrocutaneous branchial remnants (CCBR) and trichofolliculoma. With hematoxylin and eosin stain, HFN showed numerous tiny hair follicles in the dermis with several sebaceous and eccrine glands, and perifollicular fibrous thickening. With CK19 stain, some hair follicles in HFN and CCBR showed positive expression, a few hair follicles in accessory tragus showed weak expression, and no hair follicles in trichofolliculoma showed expression. The present report supports the view that HFN, accessory tragus and CCBR are within the same spectrum of hamartomas.

15.
J Dermatol ; 46(12): 1210-1214, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31642108

RESUMO

Medicolegal disputes are increasing in practical medicine. Medications or procedures related to acne could lead to medical malpractice. This study analyzed medical litigation associated with acne in South Korea. Acne-related judgments were searched using the Supreme Court of Korea's Written Judgment Management System based on the keyword "acne". Eleven cases were selected; eight cases were related to acne scar and three cases were related to acne. Treatment modalities such as peeling, laser treatment, photodynamic therapy and antibiotics resulted in lawsuits. Claimed sequelae of the treatments were hyperpigmentation, scar worsening, erythema, skin bumps and liver transplant. Eight cases were awarded to the plaintiff, and the others were dismissed. This study shows that various treatments for acne can cause medical disputes.


Assuntos
Acne Vulgar/terapia , Dermatologia/legislação & jurisprudência , Imperícia/estatística & dados numéricos , Adolescente , Adulto , Feminino , Humanos , Masculino
16.
Mol Cells ; 25(3): 358-67, 2008 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-18443423

RESUMO

The embryonic germ cell (EGCs) of mice is a kind of pluripotent stem cell that can be generated from pre- and post-migratory primordial germ cells (PGCs). Most previous studies on DNA methylation of EGCs were restricted to 12.5 days post coitum (dpc). This study was designed to establish and characterize murine EGC lines from migrated PGCs as late as 13.5 dpc and to estimate the degrees of methylation of their imprinted genes as well as of the non-imprinted locus, Oct4, using an accurate and quantitative method of measurement. We established five independent EGC lines from post migratory PGCs of 11.5-13.5 dpc from C57BL/6xDBA/2 F1 hybrid mouse fetuses. All the EGCs exhibited the typical features of pluripotent cells including hypomethylation of the Oct4 regulatory region. We examined the methylation status of three imprinted genes; Igf2, Igf2r and H19 in the five EGC lines using bisulfite genomic sequencing analysis. Igf2r was almost unmethylated in all the EGC lines irrespective of the their sex and stage of isolation; Igf2 and H19 were more methylated than Igf2r, especially in male EGCs. Moreover, EGCs derived at 13.5 dpc exhibited higher levels of DNA methylation than those from earlier stages. These results suggest that in vitro derived EGCs acquire different epigenotypes from their parental in vivo migratory PGCs, and that sex-specific de novo methylation occurs in the Igf2 and H19 genes of EGCs.


Assuntos
Metilação de DNA , Embrião de Mamíferos/citologia , Impressão Genômica , Células Germinativas/metabolismo , Células-Tronco Pluripotentes/metabolismo , Animais , Biomarcadores/metabolismo , Diferenciação Celular , Linhagem Celular , Células Cultivadas , Feminino , Genômica , Células Germinativas/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Pluripotentes/citologia , Elementos Reguladores de Transcrição , Sulfitos/química
17.
Ann Dermatol ; 30(5): 581-587, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33911482

RESUMO

BACKGROUND: Although many therapeutic agents have been developed, only a few drugs are known to target multiple pathogenic factors in the treatment of acne. OBJECTIVE: The purpose of this study was to identify a new drug candidate, platycodin D, which is a substance extracted from the root of Platycodon grandiflorum. METHODS: Using western blotting and Cell Counting Kit-8 assay, we studied the effects of platycodin D on SEB-1 sebocytes, fibroblasts, and keratinocytes. We investigated its effects in view of lipogenesis, collagen production, anti-inflammatory activity, and dyskeratinization. RESULTS: In SEB-1 sebocytes, platycodin D showed a sebosuppressive effect by downregulating ERK and insulin- like growth factor-1R/PI3K/Akt/sterol-regulatory element binding protein-1 signaling pathways. In addition, adiponectin, one of the adipokines responsible for sebum production, was decreased in platycodin D-treated SEB-1 sebocytes. In fibroblasts, platycodin D increased collagen production and reduced inflammation by inhibiting nuclear factor kappa B and matrix metalloproteinases. Platycodin D also showed anti-inflammatory effects on keratinocytes. It also suppressed keratin 16 expression induced by lipopolysaccharide. Furthermore, platycodin D showed no cytotoxicity on both SEB-1 sebocytes and fibroblasts. CONCLUSION: Our data demonstrate the clinical feasibility of platycodin D for acne treatment and the prevention of acne scarring by sebosuppressive and anti-inflammatory effects, as well as through an increase in collagen levels.

18.
Arch Dermatol Res ; 310(8): 665-673, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30167815

RESUMO

Acne vulgaris is a universal skin disease and it may leave a scar when the original skin lesion disappears. These scars can cause cosmetic problems and psychological burden, leading to poor quality of life of patients. Acne scars are classified into atrophic scars and hypertrophic scars. As most of the acne scars are atrophic, many studies have been conducted focusing on the treatment of atrophic lesions. This study was conducted to investigate the underlying pathogenesis of acne hypertrophic scars by identifying roles of fibrogenetic and inflammatory markers. Skin biopsy samples were obtained from hypertrophic scars of face and back and from adjacent normal tissues as control group. Some samples from back were immature hypertrophic scars and the other samples were in mature stages. Immunohistochemistry staining and quantitative PCR were performed for fibrogenetic and inflammatory markers. Both in mature and immature hypertrophic scars, vimentin and α-SMA were increased. Production of TGF-ß3 protein as well as transcription of TGF-ß3 was also significantly elevated. In contrast, expression of TGF-ß1 showed no increase. Instead, expression levels of SMAD2 and SMAD4 were increased. Elevations of CD45RO, TNF-α and IL-4 and reduction of IL-10 were observed. In immature hypertrophic scars, IGF-1R and insulin-degrading enzyme expression were increased. Increased apoptosis was observed in immature stages of hypertrophic scars but not in mature stages. Elevations of TGF-ß3, SMAD2 and SMAD4 in hypertrophic scars and increase of IGF-1R in immature stages may give some clues for acne hypertrophic scar formation.


Assuntos
Acne Vulgar/metabolismo , Cicatriz Hipertrófica/metabolismo , Receptores de Somatomedina/análise , Pele/química , Fator de Crescimento Transformador beta3/análise , Acne Vulgar/genética , Acne Vulgar/patologia , Adulto , Apoptose , Estudos de Casos e Controles , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/patologia , Feminino , Humanos , Masculino , Receptor IGF Tipo 1 , Transdução de Sinais , Pele/patologia , Proteína Smad2/análise , Proteína Smad4/análise , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta3/genética , Adulto Jovem
19.
Ann Dermatol ; 30(6): 712-715, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33911513

RESUMO

Desmoplastic fibroblastoma is a rare fibrous tumor that usually presents as a painless, slow-growing mass in the subcutaneous tissues and skeletal muscles. It has a wide anatomic distribution, with the most common involvement being the arm and shoulder. Here, we report a case of a tiny painful desmoplastic fibroblastoma arising on the scalp. According to a microscopic examination, this tumor was composed of spindle-shaped fibroblasts in the dense collagenous stroma. On immunohistochemical staining, tumor cells were positive for vimentin and negative for smooth muscle actin, CD34, and S100. Our case is unique in that desmoplastic fibroblastoma developed on the scalp and there was presence of pain despite its small size.

20.
Sci Rep ; 8(1): 3760, 2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29491373

RESUMO

The current anticorrosion strategy makes use of coatings to passively protect the steel, which faces increasing challenge due to the tightened environmental regulations and high cost. This paper reports a new method for achieving a super anticorrosion function in Al-Si alloys through Mg nano-metallurgy, which was characterized by real-time synchrotron measurements. The unique function is based on the formation of an amorphous and self-charge-compensated MgAl2O4-SiO2 phase between the grain boundaries to help prevent the penetration of oxygen species through the grain boundaries. Through this, the corrosion resistance of pristine aluminized steel could be improved almost 20 fold. An analysis of the phases, microstructures of the Mg-coated aluminized layer and corrosion products consistently supported the proposed mechanism. This charge-compensated corrosion resistance mechanism provides novel insight into corrosion resistance.

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