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1.
Ann Surg ; 274(4): 627-636, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34506318

RESUMO

OBJECTIVE: Demonstrate the impact of IL-10 producing T lymphocytes on mediating dermal scarring. SUMMARY BACKGROUND DATA: We demonstrated that CD4+ cells are essential to improving postinjury wound healing and preventing fibrosis. CD4+ subsets secrete differential cytokine and growth factor profiles, though their role in fibrosis is not known. IL-10, a key anti-inflammatory cytokine shown to promote regenerative wound healing, is secreted by some CD4+ subsets. We, therefore, hypothesize that IL-10 producing CD4+ T lymphocyte subsets selectively attenuate dermal wound fibrosis. METHODS: IL-10-/- and wild-type murine splenocytes were enriched for CD4+ lymphocytes and adoptively transferred into severe combined immunodeficient (SCID) mice that received full-thickness wounds which were analyzed at days 7 and 28 for inflammation and collagen content. We then sorted CD4+CD44int/lowFoxP3-CD62L+ T cells (Tnaive) or CD4+CD44HiFoxP3- type 1 regulatory (Tr1) T cell subsets from 10BiT murine splenocytes, activated them, and transferred them into wounds. In vitro, dermal fibroblasts were cocultured with Tnaive or Tr1 and the effect on extracellular matrix (ECM) regulation was analyzed. RESULTS: The anti-inflammatory and antifibrotic effects of CD4+ cells on SCID wounds were lost with cells from IL-10-/- mice. Adoptive transfer of Tr1 into SCID mice resulted in accelerated wound closure at d7 with reduced fibrosis at d28, with Tr1 favoring hyaluronan production by fibroblasts, an ECM molecule implicated in IL-10-induced regenerative healing. CONCLUSIONS: IL-10 producing T-lymphocytes, specifically Tr1, regulate inflammatory cell cytokine expression to promote HA-rich ECM deposition and attenuate fibrosis. Promoting IL-10 producing lymphocytes in wounds may be a therapeutic target to promote regenerative wound healing.


Assuntos
Linfócitos T CD4-Positivos/fisiologia , Cicatriz/patologia , Cicatriz/prevenção & controle , Derme/lesões , Interleucina-10/fisiologia , Cicatrização/fisiologia , Transferência Adotiva , Animais , Cicatriz/etiologia , Derme/patologia , Modelos Animais de Doenças , Camundongos , Camundongos SCID
2.
Int J Mol Sci ; 22(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34445299

RESUMO

Deep partial-thickness burns damage most of the dermis and can cause severe pain, scarring, and mortality if left untreated. This study serves to evaluate the effectiveness of crosslinked keratin-alginate composite sponges as dermal substitutes for deep partial-thickness burns. Crosslinked keratin-alginate sponges were tested for the ability to support human dermal fibroblasts in vitro and to support the closure and healing of partial-thickness burn wounds in Sus scrofa pigs. Keratin-alginate composite sponges supported the enhanced proliferation of human dermal fibroblasts compared to alginate-only sponges and exhibited decreased contraction in vitro when compared to keratin only sponges. As dermal substitutes in vivo, the sponges supported the expression of keratin 14, alpha-smooth muscle actin, and collagen IV within wound sites, comparable to collagen sponges. Keratin-alginate composite sponges supported the regeneration of basement membranes in the wounds more than in collagen-treated wounds and non-grafted controls, suggesting the subsequent development of pathological scar tissues may be minimized. Results from this study indicate that crosslinked keratin-alginate sponges are suitable alternative dermal substitutes for clinical applications in wound healing and skin regeneration.


Assuntos
Alginatos/uso terapêutico , Queimaduras/terapia , Queratinas/uso terapêutico , Cicatrização , Alginatos/química , Alginatos/farmacologia , Animais , Curativos Hidrocoloides , Queimaduras/patologia , Queimaduras/fisiopatologia , Células Cultivadas , Derme/efeitos dos fármacos , Derme/patologia , Derme/fisiopatologia , Humanos , Hidrogéis/química , Hidrogéis/uso terapêutico , Queratinas/química , Queratinas/farmacologia , Masculino , Teste de Materiais , Índice de Gravidade de Doença , Pele/efeitos dos fármacos , Pele/patologia , Pele/fisiopatologia , Suínos , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia
3.
Nutrients ; 13(7)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34371956

RESUMO

We examined the immunomodulatory and anti-inflammatory effects of asiatic acid (AA) in atopic dermatitis (AD). AA treatment (5-20 µg/mL) dose-dependently suppressed the tumor necrosis factor (TNF)-α level and interleukin (IL)-6 protein expression in interferon (IFN)-γ + TNF-α-treated HaCaT cells. The 2,4-dinitrocholrlbenzene (DNCB)-induced AD animal model was developed by administering two AA concentrations (30 and 75 mg/kg/d: AD + AA-L and AD + AA-H groups, respectively) for 18 days. Interestingly, AA treatment decreased AD skin lesions formation and affected other AD characteristics, such as increased ear thickness, lymph node and spleen size, dermal and epidermal thickness, collagen deposition, and mast cell infiltration in dorsal skin. In addition, in the DNCB-induced AD animal model, AA treatment downregulated the mRNA expression level of AD-related cytokines, such as Th1- (TNF-α and IL-1ß and -12) and Th2 (IL-4, -5, -6, -13, and -31)-related cytokines as well as that of cyclooxygenase-2 and CXCL9. Moreover, in the AA treatment group, the protein level of inflammatory cytokines, including COX-2, IL-6, TNF-α, and IL-8, as well as the NF-κB and MAPK signaling pathways, were decreased. Overall, our study confirmed that AA administration inhibited AD skin lesion formation via enhancing immunomodulation and inhibiting inflammation. Thus, AA can be used as palliative medication for regulating AD symptoms.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Citocinas/metabolismo , Dermatite Atópica/tratamento farmacológico , Fatores Imunológicos/farmacologia , Triterpenos Pentacíclicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Linhagem Celular , Sobrevivência Celular , Colágeno/análise , Citocinas/genética , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Derme/patologia , Dinitroclorobenzeno , Modelos Animais de Doenças , Epiderme/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêutico , Imunomodulação , Tecido Linfoide/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mastócitos , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Triterpenos Pentacíclicos/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
4.
Int J Mol Sci ; 22(11)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199947

RESUMO

Particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5) increases oxidative stress through free radical generation and incomplete volatilization. In addition to affecting the respiratory system, PM2.5 causes aging- and inflammation-related damage to skin. Farnesol (Farn), a natural benzyl semiterpene, possesses anti-inflammatory, antioxidative, and antibacterial properties. However, because of its poor water solubility and cytotoxicity at high concentrations, the biomedical applications of Farn have been limited. This study examined the deleterious effects of PM2.5 on the epidermis and dermis. In addition, Farn-encapsulated liposomes (Lipo-Farn) and gelatin/HA/xanthan gel containing Lipo-Farn were prepared and applied in vivo to repair and alleviate PM2.5-induced damage and inflammation in skin. The prepared Lipo-Farn was 342 ± 90 nm in diameter with an encapsulation rate of 69%; the encapsulation significantly reduced the cytotoxicity of Farn. Lipo-Farn exhibited a slow-release rate of 35% after 192 h of incubation. The half-maximal inhibitory concentration of PM2.5 was approximately 850 µg/mL, and ≥400 µg/mL PM2.5 significantly increased IL-6 production in skin fibroblasts. Severe impairment in the epidermis and hair follicles and moderate impairment in the dermis were found in the groups treated with post-PM2.5 and continuous subcutaneous injection of PM2.5. Acute and chronic inflammation was observed in the skin in both experimental categories in vivo. Treatment with 4 mM Lipo-Farn largely repaired PM2.5-induced injury in the epidermis and dermis, restored injured hair follicles, and alleviated acute and chronic inflammation induced by PM2.5 in rat skin. In addition, treatment with 4 mM pure Farn and 2 mM Lipo-Farn exerted moderate reparative and anti-inflammatory effects on impaired skin. The findings of the current study indicate the therapeutic and protective effects of Lipo-Farn against various injuries caused by PM2.5 in the pilosebaceous units, epidermis, and dermis of skin.


Assuntos
Derme/efeitos dos fármacos , Epiderme/efeitos dos fármacos , Farneseno Álcool/farmacologia , Lipossomos/administração & dosagem , Material Particulado/toxicidade , Substâncias Protetoras/farmacologia , Dermatopatias/tratamento farmacológico , Animais , Antioxidantes , Derme/patologia , Epiderme/patologia , Feminino , Lipossomos/química , Ratos , Ratos Sprague-Dawley , Dermatopatias/induzido quimicamente , Dermatopatias/patologia
5.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298962

RESUMO

We studied CD34+ stromal cells/telocytes (CD34+SCs/TCs) in pathologic skin, after briefly examining them in normal conditions. We confirm previous studies by other authors in the normal dermis regarding CD34+SC/TC characteristics and distribution around vessels, nerves and cutaneous annexes, highlighting their practical absence in the papillary dermis and presence in the bulge region of perifollicular groups of very small CD34+ stromal cells. In non-tumoral skin pathology, we studied examples of the principal histologic patterns in which CD34+SCs/TCs have (1) a fundamental pathophysiological role, including (a) fibrosing/sclerosing diseases, such as systemic sclerosis, with loss of CD34+SCs/TCs and presence of stromal cells co-expressing CD34 and αSMA, and (b) metabolic degenerative processes, including basophilic degeneration of collagen, with stromal cells/telocytes in close association with degenerative fibrils, and cutaneous myxoid cysts with spindle-shaped, stellate and bulky vacuolated CD34+ stromal cells, and (2) a secondary reactive role, encompassing dermatitis-e.g., interface (erythema multiforme), acantholytic (pemphigus, Hailey-Hailey disease), lichenoid (lichen planus), subepidermal vesicular (bullous pemphigoid), psoriasiform (psoriasis), granulomatous (granuloma annulare)-vasculitis (leukocytoclastic and lymphocytic vasculitis), folliculitis, perifolliculitis and inflammation of the sweat and sebaceous glands (perifolliculitis and rosacea) and infectious dermatitis (verruca vulgaris). In skin tumor and tumor-like conditions, we studied examples of those in which CD34+ stromal cells are (1) the neoplastic component (dermatofibrosarcoma protuberans, sclerotic fibroma and solitary fibrous tumor), (2) a neoplastic component with varying presentation (fibroepithelial polyp and superficial myxofibrosarcoma) and (3) a reactive component in other tumor/tumor-like cell lines, such as those deriving from vessel periendothelial cells (myopericytoma), epithelial cells (trichoepithelioma, nevus sebaceous of Jadassohn and seborrheic keratosis), Merkel cells (Merkel cell carcinoma), melanocytes (dermal melanocytic nevi) and Schwann cells (neurofibroma and granular cell tumor).


Assuntos
Antígenos CD34/metabolismo , Dermatite/metabolismo , Derme/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Cutâneas/metabolismo , Telócitos/metabolismo , Animais , Dermatite/patologia , Derme/patologia , Humanos , Neoplasias Cutâneas/patologia , Telócitos/patologia
6.
Am J Surg Pathol ; 45(10): 1357-1363, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34324455

RESUMO

Herpes viruses are known for infecting epithelial cells and manifesting as vesicles. However, herpes viruses can also infect stromal cells. While established in the ocular setting, cutaneous stromal herpes (deep herpes) is previously unreported and may evade clinical and microscopic detection. We searched for skin biopsies with herpes stromal disease. Clinical information was retrieved via electronic medical records and pathology records system. Hematoxylin and eosin slides, immunohistochemical staining, and polymerase chain reaction detection of viral DNA was performed. We identified 12 specimens from 10 patients with cutaneous stromal herpes simplex virus 1/2 (n=7) or varicella-zoster virus infection (n=5). The most common site involved was the buttocks/perianal region (n=6). Ulceration was a frequent dermatologic finding (n=8). Pyoderma gangrenosum was clinically suspected in 6 specimens (50%). Eight patients (80%) were immunosuppressed. Biopsies frequently demonstrated a dense dermal mixed inflammatory infiltrate with subcutaneous extension and enlarged cells with viral cytopathic changes confirmed by herpes simplex virus 1/2 or varicella-zoster virus immunohistochemistry (n=10) or polymerase chain reaction (n=2). Most specimens (67%) lacked evidence of characteristic epidermal keratinocyte infection. This study presents the first known report of the ability of herpes virus to infect deep stromal cells of the dermis. We raise awareness of cutaneous stromal herpes in patients presenting with atypical clinical lesions, particularly while immunocompromised. Establishing the correct diagnosis is critical for initiating therapy.


Assuntos
Derme/virologia , Herpes Simples/virologia , Herpesvirus Humano 1/patogenicidade , Herpesvirus Humano 2/patogenicidade , Herpesvirus Humano 3/patogenicidade , Células Estromais/virologia , Infecção pelo Vírus da Varicela-Zoster/virologia , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , DNA Viral/genética , Derme/efeitos dos fármacos , Derme/patologia , Feminino , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/efeitos dos fármacos , Herpesvirus Humano 2/genética , Herpesvirus Humano 3/efeitos dos fármacos , Herpesvirus Humano 3/genética , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Células Estromais/efeitos dos fármacos , Células Estromais/patologia , Resultado do Tratamento , Infecção pelo Vírus da Varicela-Zoster/diagnóstico , Infecção pelo Vírus da Varicela-Zoster/tratamento farmacológico , Adulto Jovem
7.
Int J Mol Sci ; 22(11)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073402

RESUMO

The development of scaffolds mimicking the extracellular matrix containing bioactive substances has great potential in tissue engineering and wound healing applications. This study investigates melatonin-a methoxyindole present in almost all biological systems. Melatonin is a bioregulator in terms of its potential clinical importance for future therapies of cutaneous diseases. Mammalian skin is not only a prominent melatonin target, but also produces and rapidly metabolizes the multifunctional methoxyindole to biologically active metabolites. In our methodology, chitosan/collagen (CTS/Coll)-contained biomaterials are blended with melatonin at different doses to fabricate biomimetic hybrid scaffolds. We use rat tail tendon- and Salmo salar fish skin-derived collagens to assess biophysical and cellular properties by (i) Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), (ii) thermogravimetric analysis (TG), (iii) scanning electron microscope (SEM), and (iv) proliferation ratio of cutaneous cells in vitro. Our results indicate that melatonin itself does not negatively affect biophysical properties of melatonin-immobilized hybrid scaffolds, but it induces a pronounced elevation of cell viability within human epidermal keratinocytes (NHEK), dermal fibroblasts (NHDF), and reference melanoma cells. These results demonstrate that this indoleamine accelerates re-epithelialization. This delivery is a promising technique for additional explorations in future dermatotherapy and protective skin medicine.


Assuntos
Bandagens , Quitosana/química , Colágeno/química , Derme/metabolismo , Epiderme/metabolismo , Fibroblastos/metabolismo , Queratinócitos/metabolismo , Melatonina , Linhagem Celular , Derme/patologia , Avaliação Pré-Clínica de Medicamentos , Epiderme/patologia , Fibroblastos/patologia , Humanos , Queratinócitos/patologia , Melatonina/química , Melatonina/farmacocinética , Melatonina/farmacologia
8.
Bioengineered ; 12(1): 2592-2602, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34124997

RESUMO

Long non-coding RNAs (lncRNAs) were considered to be involved in vascular complications in diabetes mellitus, but still only limited knowledge in this regard has been obtained. Herein, we further explored the roles of lncRNAs and mRNAs in diabetic vasculopathy (DV) through conducting bioinformatics analysis using data set downloaded from GEO database. The differentially expressed lncRNAs and mRNAs were identified by edge package. GO enrichment analysis and KEGG pathway analysis were performed based on clusterprofiler package. The relationship between lncRNA and miRNA was predicted using starBase database, and the potential mRNAs targeted by miRNAs were predicted by TargetScan, miRTarbase and miRDB database. The string database was used to analyze the protein-protein interaction (PPI). As a result, a total of 12 lncRNAs and 711 mRNAs were found to be differentially expressed in the diabetic subdermal endothelial cells compared with normal controls. A ceRNA network was established, which was composed of seven lncRNA nodes, 49 miRNA nodes, 58 mRNA nodes and 183 edges, and MSC-AS1 and LINC01550 may serve as key nodes. GO function enrichment analysis showed enrichments of epithelial cell proliferation, intercellular junction, and cell adhesion molecule binding. KEGG pathway analysis revealed 33 enriched pathways. PPI protein interaction analysis identified 57 potential ceRNA-related proteins. Overall, this study suggests that multiple lncRNAs, specifically MSC-AS1 and LINC01550, may play an important role in DV development and they are like to be developed as the therapeutic targets for DV. However, further experiments in vitro and in vivo should be conducted to validate our results.


Assuntos
Derme/patologia , Diabetes Mellitus/genética , Diabetes Mellitus/patologia , Células Endoteliais/metabolismo , Redes Reguladoras de Genes , RNA Longo não Codificante/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Frações Subcelulares/metabolismo
9.
Sci Rep ; 11(1): 13234, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34168195

RESUMO

The skin barrier is provided by the organized multi-layer structure of epidermal cells, which is dynamically maintained by a continuous supply of cells from the basal layer. The epidermal homeostasis can be disrupted by various skin diseases, which often cause morphological changes not only in the epidermis but in the dermis. We present a three-dimensional agent-based computational model of the epidermis that takes into account the deformability of the dermis. Our model can produce a stable epidermal structure with well-organized layers. We show that its stability depends on the cell supply rate from the basal layer. Modeling the morphological change of the dermis also enables us to investigate how the stiffness of the dermis affects the structure and barrier functions of the epidermis. Besides, we show that our model can simulate the formation of a corn (clavus) by assuming hyperproliferation and rapid differentiation. We also provide experimental data for human corn, which supports the model assumptions and the simulation result.


Assuntos
Derme/patologia , Epiderme/patologia , Dermatopatias/patologia , Simulação por Computador , Homeostase , Humanos
10.
Mol Cell Biochem ; 476(10): 3613-3622, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34028646

RESUMO

Molecular hydrogen (H2) is recognized as a gaseous antioxidant, and it is expected to ameliorate various disorders related to oxidative stress and inflammation. However, there are still many unclear points regarding its effectiveness in the skin. Therefore, the purpose of this study was to examine the protective effect of H2 against ultraviolet (UV) irradiation-related stress injury in human epidermal HaCaT cells. We investigated the effects of H2 against three types of UV-derived oxidative stress using human skin keratinocytes: hydrogen peroxide (H2O2)-induced oxidative stress, tert-butyl hydroperoxide (t-BuOOH)-induced lipid peroxidation stress, and glyoxal-induced carbonyl stress. Our results showed that H2 exerted cytoprotective effects against stress induced by H2O2, t-BuOOH, and glyoxal. Furthermore, our results also revealed that H2 suppressed H2O2-induced increases in intracellular peroxide and H2O2 levels, and suppressed the progression of lipid peroxidation. Taken together, our results demonstrate that H2 can exert protective effects against oxidative stress-, lipid peroxidation-, and carbonyl stress-induced cellular injuries in human keratinocytes, partly mediated via suppression of intracellular oxidative stress and peroxide generation. Therefore, H2 is expected to be utilized as an effective and attractive component in cosmetic formulations in the future.


Assuntos
Derme/lesões , Glioxal/toxicidade , Peróxido de Hidrogênio/toxicidade , Hidrogênio/farmacologia , Queratinócitos/metabolismo , Linhagem Celular , Derme/metabolismo , Derme/patologia , Humanos , Queratinócitos/patologia
11.
BMC Med Genomics ; 14(1): 138, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34030677

RESUMO

BACKGROUND: Older aged adults and those with pre-existing conditions are at highest risk for severe COVID-19 associated outcomes. METHODS: Using a large dataset of genome-wide RNA-seq profiles derived from human dermal fibroblasts (GSE113957) we investigated whether age affects the expression of pattern recognition receptor (PRR) genes and ACE2, the receptor for SARS-CoV-2. RESULTS: Extremes of age are associated with increased expression of selected PRR genes, ACE2 and four genes that encode proteins that have been shown to interact with SAR2-CoV-2 proteins. CONCLUSIONS: Assessment of PRR expression might provide a strategy for stratifying the risk of severe COVID-19 disease at both the individual and population levels.


Assuntos
COVID-19/genética , COVID-19/virologia , Regulação da Expressão Gênica , Peptidil Dipeptidase A/genética , Receptores de Reconhecimento de Padrão/genética , Receptores Virais/genética , SARS-CoV-2/metabolismo , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Derme/patologia , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , RNA-Seq , Receptores Virais/metabolismo , Adulto Jovem
12.
Indian J Pathol Microbiol ; 64(2): 323-328, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33851627

RESUMO

Background: Primary cutaneous amyloidosis (PCA) comprises several forms of localized cutaneous amyloidosis characterized by amyloid deposits occurring at or near dermal-epidermal junctions. Immunohistochemical studies have shown the expression of cytokeratin (CK) suggesting that it has an epidermal origin. Objectives: To study the clinicopathological features of PCA and expression of CK5/6 and correlate it with Congo red stain. Materials and Methods: A total of 30 histologically proven cases of PCA were studied. Congo red staining and immunohistochemical expression of CK5/6 were analyzed. Statistical Analysis: : The qualitative data has been expressed as proportions and the quantitative data has been expressed as mean ± SD. All data was analyzed using the Statistical Package for Social Sciences (SPSS) software version 22. Results: Deposits of amyloid in papillary dermis were seen in all 30 cases. Mild focal basal cell vacuolar degeneration and apoptotic bodies in epidermis were seen in six cases. The presence of pigment cells in dermis were seen in 26 cases. CK5/6 showed weak/mild immunopositivity in nine cases, moderate in 20 cases, and strong in one case. Conclusion: The presence of dermal melanophages interspersed within eosinophilic deposits gives a clue to the diagnosis. Congo red stain highlights the deposits and visualization under polarized light gives apple green birefringence which is diagnostic of amyloid. Staining of amyloid deposits by CK5/6 proves that the amyloid is of keratinocyte origin. There was 100% sensitivity with Congo red and CK5/6. Thus, CK5/6 can be used as an adjunct tool to Congo red stain in the diagnosis of primary cutaneous amyloidosis.


Assuntos
Amiloide/metabolismo , Amiloidose Familiar/diagnóstico , Amiloidose Familiar/patologia , Epiderme/patologia , Queratinas/metabolismo , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vermelho Congo , Derme/patologia , Feminino , Humanos , Imuno-Histoquímica , Queratinócitos/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Coloração e Rotulagem , Adulto Jovem
13.
Indian J Pathol Microbiol ; 64(2): 398-401, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33851645

RESUMO

Malignant eccrine spiradenoma is an extremely rare neoplasm of adnexal origin. It almost always originates from a preexisting long standing eccrine spiradenoma. We present a case of malignant eccrine spiradenoma arising from benign counterpart and having both carcinomatous and sarcomatous differentiation. Here we present a case of a 46 years old lady who presented with a long standing small nodule on her left leg of 7 years' duration with suddenly increase in size. Grossly the mass was partly solid and partly cystic measuring 11.5 cm in maximum dimension with cystic area forming the deeper plane. On microscopy, the superficial dermis showed well demarcated lobules of benign eccrine spiradenoma. Deeper dermis showed tumor cells with features of malignant transformation having both carcinomatous and sarcomatous component. After wide local excision patient is now doing well. The diagnosis of malignant eccrine spiradenoma requires a thorough histopathological examination of the lesion and requires finding a focus of benign spiradenoma within or adjacent to malignant tumour. Wide local excision and close follow-up for early detection of recurrence and metastasis is the mostly recommended management modality.


Assuntos
Acrospiroma/diagnóstico , Acrospiroma/patologia , Carcinossarcoma/diagnóstico , Carcinossarcoma/patologia , Neoplasias das Glândulas Sudoríparas/diagnóstico , Neoplasias das Glândulas Sudoríparas/patologia , Derme/patologia , Diagnóstico Diferencial , Feminino , Humanos , Perna (Membro)/patologia , Pessoa de Meia-Idade , Glândulas Sudoríparas/patologia
14.
J Am Acad Dermatol ; 85(1): 18-27, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33684494

RESUMO

Subepidermal (subepithelial) autoimmune blistering dermatoses are a group of rare skin disorders characterized by the disruption of the dermal-epidermal junction through the action of autoantibodies. The fourth article in this continuing medical education series presents the current validated disease activity scoring systems, serologic parameters, treatments, and clinical trials for bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, bullous systemic lupus erythematosus, anti-p200 pemphigoid, linear IgA bullous dermatosis, and dermatitis herpetiformis.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Fotoquimioterapia/métodos , Dermatopatias Vesiculobolhosas/tratamento farmacológico , Administração Cutânea , Administração Oral , Autoanticorpos/imunologia , Doenças Autoimunes/sangue , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Biomarcadores/sangue , Ensaios Clínicos como Assunto , Citocinas/sangue , Citocinas/imunologia , Derme/imunologia , Derme/patologia , Quimioterapia Combinada/métodos , Glucocorticoides/administração & dosagem , Humanos , Índice de Gravidade de Doença , Dermatopatias Vesiculobolhosas/sangue , Dermatopatias Vesiculobolhosas/diagnóstico , Dermatopatias Vesiculobolhosas/imunologia , Resultado do Tratamento
15.
J Am Acad Dermatol ; 85(1): 1-14, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33684496

RESUMO

Subepithelial autoimmune blistering dermatoses are a group of rare skin disorders that are characterized by the disruption of the dermal-epidermal junction through the action of autoantibodies. The third article in this continuing medical education series explores the background, epidemiology, clinical features, and diagnostic criteria of each of the major subepithelial autoimmune blistering dermatoses, including bullous pemphigoid, pemphigoid gestationis, lichen planus pemphigoides, mucous membrane pemphigoid, linear IgA bullous dermatosis, and dermatitis herpetiformis.


Assuntos
Doenças Autoimunes/diagnóstico , Líquen Plano/diagnóstico , Penfigoide Gestacional/diagnóstico , Dermatopatias Vesiculobolhosas/diagnóstico , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Derme/imunologia , Derme/patologia , Feminino , Humanos , Líquen Plano/epidemiologia , Líquen Plano/imunologia , Líquen Plano/patologia , Penfigoide Gestacional/epidemiologia , Penfigoide Gestacional/imunologia , Penfigoide Gestacional/patologia , Gravidez , Dermatopatias Vesiculobolhosas/epidemiologia , Dermatopatias Vesiculobolhosas/imunologia , Dermatopatias Vesiculobolhosas/patologia
16.
Int J Mol Sci ; 22(4)2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33670258

RESUMO

The recessive form of dystrophic epidermolysis bullosa (RDEB) is a debilitating disease caused by impairments in the junctions of the dermis and the basement membrane of the epidermis. Mutations in the COL7A1 gene induce multiple abnormalities, including chronic inflammation and profibrotic changes in the skin. However, the correlations between the specific mutations in COL7A1 and their phenotypic output remain largely unexplored. The mutations in the COL7A1 gene, described here, were found in the DEB register. Among them, two homozygous mutations and two cases of compound heterozygous mutations were identified. We created the panel of primary patient-specific RDEB fibroblast lines (FEB) and compared it with control fibroblasts from healthy donors (FHC). The set of morphological features and the contraction capacity of the cells distinguished FEB from FHC. We also report the relationships between the mutations and several phenotypic traits of the FEB. Based on the analysis of the available RNA-seq data of RDEB fibroblasts, we performed an RT-qPCR gene expression analysis of our cell lines, confirming the differential status of multiple genes while uncovering the new ones. We anticipate that our panels of cell lines will be useful not only for studying RDEB signatures but also for investigating the overall mechanisms involved in disease progression.


Assuntos
Colágeno Tipo VII , Derme , Epidermólise Bolhosa Distrófica , Fibroblastos , Regulação da Expressão Gênica , Homozigoto , Mutação , Adolescente , Adulto , Criança , Colágeno Tipo VII/biossíntese , Colágeno Tipo VII/genética , Derme/metabolismo , Derme/patologia , Epidermólise Bolhosa Distrófica/genética , Epidermólise Bolhosa Distrófica/metabolismo , Epidermólise Bolhosa Distrófica/patologia , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Masculino , Pessoa de Meia-Idade
17.
Exp Biol Med (Maywood) ; 246(6): 718-728, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33706582

RESUMO

Intractable wound healing is the habitual problem of diabetes mellitus. High blood glucose limits wound healing by interrupting inflammatory responses and inhibiting neoangiogenesis. Oxidative stress is commonly thought to be a major pathogenic cause of diabetic complications. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one, EDV) is a free radical scavenger which suppress oxidative stress. This study investigates whether EDV can reduce oxidative stress in wound healing HaCaT/human dermal fibroblasts cells (HDFs) in vitro and in vivo animal model. Cell viability and wound healing assays, FACS flow cytometry, and Hoechst 33342 staining were performed to confirm apoptosis and cytotoxicity in H2O2 and EDV-treated HaCaT and HDFs. A streptozotocin-induced hyperglycemic animal model was made in adult C57BL6 mice. Full-thickness skin flap was made on dorsomedial back and re-sutured to evaluate the wound healing process. EDV was delivered slowly in the skin flap with degradable fibrin glue. The flap was monitored and analyzed on postoperative days 1, 3, and 5. CD31/DAPI staining was done to detect newly formed blood vessels. The expression levels of NF-κB, bcl-2, NOX3, and STAT3 proteins in C57BL6 mouse tissues were also examined. The wound healing process in hyper- and normoglycemic mice showed a difference in protein expression, especially in oxidative stress management and angiogenesis. Exogenous H2O2 reduced cell viability in a proportion to the concentration via apoptosis. EDV protected HaCaT cells and HDFs from H2O2 induced reactive oxygen species cell damage and apoptosis. In the mouse model, EDV with fibrin resulted in less necrotic areas and increased angiogenesis on postoperative day 5, compared to sham-treated mice. Our results indicate that EDV could protect H2O2-induced cellular injury via inhibiting early apoptosis and inflammation and also increasing angiogenesis. EDV might be valuable in the treatment of diabetic wounds that oxidative stress has been implicated.


Assuntos
Apoptose , Diabetes Mellitus Experimental/patologia , Neovascularização Fisiológica , Pele/irrigação sanguínea , Pele/patologia , Administração Tópica , Animais , Apoptose/efeitos dos fármacos , Bovinos , Derme/patologia , Diabetes Mellitus Experimental/complicações , Modelos Animais de Doenças , Edaravone/administração & dosagem , Edaravone/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Células HaCaT , Humanos , Hiperglicemia/complicações , Hiperglicemia/patologia , Masculino , Camundongos Endogâmicos C57BL , Necrose , Neovascularização Fisiológica/efeitos dos fármacos , Oxirredução , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Cicatrização/efeitos dos fármacos
18.
J Cutan Pathol ; 48(7): 961-964, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33713046

RESUMO

We report an unique case of a patient who showed coexistence of three nevus lipomatosus cutaneus superficialis (NLCS) with typical, cutaneous adenolipoma (AL)-like, and dermal spindle cell lipoma (SCL)-like histopathological features. A 53-year-old woman presented with a 20-year history of skin-colored and slightly elevated nodules. These lesions were separately located on the lateral side (lesion 1) and medial side (lesion 2) of her left buttock and on her right thigh (lesion 3). Microscopically, all were ill-defined dermal lesions with some subcutaneous involvement and were mostly composed of mature adipocytes. The adipocytes formed small aggregates around blood vessels in the upper dermis. Lesions 1, 2, and 3 were diagnosed as NLCS, and additional features were recognized in lesions 2 and 3. Lesion 2 revealed eccrine glands and ducts amongst the lipomatous component, as seen in cutaneous AL. Lesion 3 had scattered CD34-positive spindle cells, which is representative of dermal SCL. These appearances were considered to be on the morphological spectrum of NLCS. In all three lesions, CD34-positive cells proliferated between the upper dermal blood vessels and their peripheral mature adipocytes. This pathological finding could be principal in NLCS and might be associated with its pathogenesis.


Assuntos
Adenoma/diagnóstico , Lipoma/diagnóstico , Neoplasias Primárias Múltiplas/patologia , Nevo/diagnóstico , Neoplasias Cutâneas/patologia , Adenoma/metabolismo , Adenoma/patologia , Adipócitos/patologia , Antígenos CD34/metabolismo , Vasos Sanguíneos/patologia , Nádegas/patologia , Derme/irrigação sanguínea , Derme/patologia , Glândulas Écrinas/patologia , Feminino , Humanos , Lipoma/metabolismo , Lipoma/patologia , Pessoa de Meia-Idade , Nevo/metabolismo , Nevo/patologia , Neoplasias Cutâneas/ultraestrutura , Coxa da Perna/patologia
19.
J Invest Dermatol ; 141(4S): 1096-1103, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541724

RESUMO

As a barrier organ, the skin is an ideal model to study environmentally-induced (extrinsic) aging. In this review, we explain the development of extrinsic skin aging as a consequence of skin exposure to specific exposomal factors, their interaction with each other, and the modification of their effects on the skin by genetic factors. We also review the evidence that exposure to these exposomal factors causes extrinsic skin aging by mechanisms that critically involve the accumulation of macromolecular damage and the subsequent development of functionally altered and/or senescent fibroblasts in the dermal compartment of the skin.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Senescência Celular , Exposição Ambiental/efeitos adversos , Envelhecimento da Pele , Raios Ultravioleta/efeitos adversos , Senescência Celular/efeitos dos fármacos , Senescência Celular/efeitos da radiação , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Derme/citologia , Derme/efeitos dos fármacos , Derme/patologia , Derme/efeitos da radiação , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Fibroblastos/efeitos da radiação , Humanos , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação
20.
J Cutan Pathol ; 48(7): 915-924, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33586183

RESUMO

"Cutaneous melanocytic tumor with CRTC1-TRIM11 fusion" (CMTCT) is a newly described, potentially novel entity that typically presents as a dermal nodule on the head and neck, extremities, and trunk of adults. Histopathologically, it is reported as a nodular or multinodular tumor composed of epithelioid and spindle cells that are variably immunoreactive for S100-protein, SOX10, and MITF along with more specific melanocytic markers such as MelanA and HMB45. With only 11 cases reported in the English literature so far, the neoplasm appears to behave in a relatively indolent fashion. Nevertheless, in one case, local recurrence and synchronous distant metastasis were evident after 13 years. Additional cases with longer follow-up are essential to determine the neoplasm's biologic behavior with more accuracy. Herein, two cases of CMTCT, one arising on the lower back of a 65-year-old female and the other on the arm of a 33-year-old female in addition to a comprehensive literature review are reported.


Assuntos
Derme/patologia , Melanócitos/metabolismo , Melanoma/patologia , Fatores de Transcrição/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Imuno-Histoquímica/métodos , Antígeno MART-1/metabolismo , Melanócitos/patologia , Melanoma/cirurgia , Fator de Transcrição Associado à Microftalmia/metabolismo , Pessoa de Meia-Idade , Proteínas S100/metabolismo , Fatores de Transcrição SOXE/metabolismo , Resultado do Tratamento , Antígeno gp100 de Melanoma/metabolismo
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