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1.
Journal of Experimental Hematology ; (6): 1885-1889, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1010054

RESUMO

Cancer-associated fibroblasts (CAF) are a key component of the tumor microenvironment, which can secrete a variety of cytokines, chemokines and growth factors, directly and indirectly support cancer cells, also alter the immune cellular environment by inhibiting the activity of immune effector cells and recruiting immunosuppressive cells, thereby allowing cancer cells to evade immune surveillance. CAF has been proven to be associated with the development, progression, and poor prognosis of solid tumors. However, the role of CAF in hematological malignancies is still unclear. This article reviews the research progress of CAF in hematological malignancies.


Assuntos
Humanos , Fibroblastos Associados a Câncer/patologia , Neoplasias/metabolismo , Neoplasias Hematológicas/metabolismo , Microambiente Tumoral , Fibroblastos/patologia
2.
Journal of Central South University(Medical Sciences) ; (12): 750-759, 2023.
Artigo em Inglês | WPRIM | ID: wpr-982345

RESUMO

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease caused by inflammatory cells. Various inflammatory cells involved in RA include fibroblast-like synoviocytes, macrophages, CD4+T-lymphocytes, B lymphocytes, osteoclasts and chondrocytes. The close interaction between various inflammatory cells leads to imbalance of immune response and disorder of the expression of mRNA in inflammatory cells. It helps to drive production of pro-inflammatory cytokines and stimulate specific antigen-specific T- and B-lymphocytes to produce autoantibodies which is an important pathogenic factor for RA. Competing endogenous RNA (ceRNA) can regulate the expression of mRNA by competitively binding to miRNA. The related ceRNA network is a new regulatory mechanism for RNA interaction. It has been found to be involved in the regulation of abnormal biological processes such as proliferation, apoptosis, invasion and release of inflammatory factors of RA inflammatory cells. Understanding the ceRNA network in 6 kinds of RA common inflammatory cells provides a new idea for further elucidating the pathogenesis of RA, and provides a theoretical basis for the discovery of new biomarkers and effective therapeutic targets.


Assuntos
Humanos , Artrite Reumatoide/genética , MicroRNAs/metabolismo , Sinoviócitos/patologia , Citocinas/metabolismo , RNA Mensageiro/metabolismo , Fibroblastos/patologia , Proliferação de Células
3.
Chinese Journal of Pathology ; (12): 827-831, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1012315

RESUMO

Objective: To investigate the clinicopathological characteristics, immunophenotype, molecular genetics and differential diagnoses of fibrocartilaginous lipomas which consist of adipose tissue, fibrocartilage and fibrous elements. Methods: The clinicopathological features, immunohistochemical profiles and molecular profiles in six cases of fibrocartilaginous lipomas diagnosed at Foshan Traditional Chinese Medicine Hospital, Fudan University Shanghai Cancer Center, the Fifth Affiliated Hospital of Zhengzhou University and the Fourth Affiliated Hospital of Harbin Medical University from January 2017 to February 2022 were included. The follow-up information, diagnosis and differential diagnoses were evaluated. Results: There were three males and three females with a median age of 53 years (range 36-69 years) at presentation. Tumors were located in the extremities, the head and neck region and trunk; and presented as painless masses that were located in the subcutaneous tissue or deep soft tissue. Grossly, three cases were well defined with thin capsule, one case was well circumscribed without capsule, two cases were surrounded by some skeletal muscle. The tumors were composed of fatty tissue with intermingled gray-white area. The tumors ranged from 1.50-5.50 cm (mean 2.92 cm). Microscopically, the hallmark of these lesions was the complex admixture of mature adipocytes, fibrocartilage and fibrous element in varying proportions; the fibrocartilage arranged in a nodular, sheet pattern with some adipocytes inside. Tumor cells had a bland appearance without mitotic activity. Immunohistochemical analysis using antibodies to SMA, desmin, S-100, SOX9, HMGA2, RB1, CD34, adipopholin was performed in six cases; the fibrocartilage was positive for S-100 and SOX9, adipocytes were positive for S-100, adipopholin and HMGA2; CD34 was expressed in the fibroblastic cells, while desmin and SMA were negative. Loss of nuclear RB1 expression was not observed. Other genetic abnormalities had not been found yet in four cases. Follow-up information was available in six cases; there was no recurrence in five, and one patient only underwent biopsy of the mass. Conclusions: Fibrocartilaginous lipoma is a benign lipomatous tumor with mature adipocytes, fibrocartilage and fibrous elements. By immunohistochemistry, they show the expression of fat and cartilage markers. No specific molecular genetics changes have been identified so far. Familiarity with its clinicopathological features helps the distinction from its morphologic mimics.


Assuntos
Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Desmina/análise , China , Lipoma/patologia , Fibroblastos/patologia , Proteínas S100/análise , Diagnóstico Diferencial , Fibrocartilagem/patologia , Biomarcadores Tumorais/análise
4.
Acta Physiologica Sinica ; (6): 515-520, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1007766

RESUMO

Pulmonary fibrosis is a severe lung interstitial disease characterized by the destruction of lung tissue structure, excessive activation and proliferation of fibroblasts, secretion and accumulation of a large amount of extracellular matrix (ECM), and impaired lung function. Due to the complexity of the disease, a suitable animal model to mimic human pulmonary fibrosis has not yet been established. Precision-cut lung slice (PCLS) has been a widely used in vitro method to study lung physiology and pathogenesis in recent years. This method is an in vitro culture technology at the level between organs and cells, because it can preserve the lung tissue structure and various types of airway cells in the lung tissue, simulate the in vivo lung environment, and conduct the observation of various interactions between cells and ECM. Therefore, PCLS can compensate for the limitations of other models such as cell culture. In order to explore the role of discoidin domain receptor 2 (DDR2) in pulmonary fibrosis, Ddr2flox/flox mice were successfully constructed. The Cre-LoxP system and PCLS technology were used to verify the deletion or knockdown of DDR2 in mouse PCLS. Transforming growth factor β1 (TGF-β1) can induce fibrosis of mouse PCLS in vitro, which can simulate the in vivo environment of pulmonary fibrosis. In the DDR2 knock down-PCLS in vitro model, the expression of various fibrosis-related factors induced by TGF-β1 was significantly reduced, suggesting that knocking down DDR2 can inhibit the formation of pulmonary fibrosis. The results provide a new perspective for the clinical study of DDR2 as a therapeutic target in pulmonary fibrosis.


Assuntos
Animais , Humanos , Camundongos , Receptor com Domínio Discoidina 2/metabolismo , Fibroblastos/patologia , Fibrose , Pulmão/patologia , Fibrose Pulmonar/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
5.
Chinese Medical Journal ; (24): 2802-2811, 2023.
Artigo em Inglês | WPRIM | ID: wpr-1007612

RESUMO

Cancer is a major threat to human health and causes death worldwide. Research on the role of radiotherapy (RT) in the treatment of cancer is progressing; however, RT not only causes fatal DNA damage to tumor cells, but also affects the interactions between tumor cells and different components of the tumor microenvironment (TME), including immune cells, fibroblasts, macrophages, extracellular matrix, and some soluble products. Some cancer cells can survive radiation and have shown strong resistance to radiation through interaction with the TME. Currently, the complex relationships between the tumor cells and cellular components that play major roles in various TMEs are poorly understood. This review explores the relationship between RT and cell-cell communication in the TME from the perspective of immunity and hypoxia and aims to identify new RT biomarkers and treatment methods in lung cancer to improve the current status of unstable RT effect and provide a theoretical basis for further lung cancer RT sensitization research in the future.


Assuntos
Humanos , Neoplasias/patologia , Neoplasias Pulmonares/complicações , Fibroblastos/patologia , Biomarcadores , Macrófagos/patologia , Hipóxia , Microambiente Tumoral
6.
Journal of Southern Medical University ; (12): 367-374, 2022.
Artigo em Chinês | WPRIM | ID: wpr-936325

RESUMO

OBJECTIVE@#To investigate the effect of triptolide (TPL) on inflammatory response and migration of fibroblast like synovial cells (FLS) in rheumatoid arthritis (RA-FLS) and the mechanism of circular noncoding RNA (circRNA) 0003353 for mediating this effect.@*METHODS@#We collected peripheral blood mononuclear cells (PBMCs) and serum samples from 50 hospitalized RA patients and 30 healthy individuals for detecting the expression of circRNA 0003353, immune and inflammatory indexes (ESR, CRP, RF, anti-CCP, IgA, IgG, IgM, C3, and C4) and DAS28 score. Cultured RA-FLS was treated with 10 ng/mL TPL and transfected with a circRNA 0003353 overexpression plasmid, and cell counting kit-8 (CCK-8) assay and Transwell assay were used to detect the changes in the viability and migration of the cells. Enzyme-linked immunosorbent assay (ELISA) was used to examine the cytokines IL-4, IL-6, and IL-17, and real-time fluorescence quantitative PCR (RT-qPCR) was performed to detect the expression of circRNA 003353; Western blotting was used to detect the expressions of p-JAK2, pSTAT3, JAK2 and STAT3 proteins in the treated cells.@*RESULTS@#The expression of circRNA 0003353 was significantly increased in PBMCs from RA patients and showed a good performance in assisting the diagnosis of RA (AUC=90.5%, P < 0.001, 95% CI: 0.83-0.98). CircRNA 0003353 expression was positively correlated with ESR, RF and DAS28 (P < 0.05). Treatment with TPL significantly decreased the expression of circRNA 0003353, suppressed the viability and migration ability, decreased the expressions of IL-6 and IL-17, and increased the expression IL-4 in cultured RA-FLS in a time-dependent manner (P < 0.01). TNF-α stimulation of RA-FLS significantly increased the ratios of p-JAK2/JAK2 and p-STAT3/STAT3, which were obviously lowered by TPL treatment (P < 0.01). TPL-treated RA-FLS overexpressing circRNA 0003353 showed significantly increased cell viability and migration ability with decreased IL-4 expression and increased IL-6 and IL-17 expressions and ratios of p-JAK2/ JAK2 and p-STAT3/STAT3 (P < 0.01).@*CONCLUSION@#The expression of circRNA 0003353 is increased in PBMCs in RA patients and in RA-FLS. TPL treatment can regulate JAK2/STAT3 signal pathway and inhibit the inflammatory response and migration of RA-FLS through circRNA 0003353.


Assuntos
Humanos , Artrite Reumatoide/patologia , Células Cultivadas , Diterpenos/farmacologia , Compostos de Epóxi/farmacologia , Fibroblastos/patologia , Interleucina-17/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Janus Quinase 2/metabolismo , Leucócitos Mononucleares/metabolismo , Fenantrenos/farmacologia , RNA Circular/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/patologia
7.
Braz. arch. biol. technol ; 64: e21200093, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1153294

RESUMO

HIGHLIGHTS Sodium arsenite can cause neoplastic transformation in cells. Curcumin reduced cell viability and increased LDH activity in transformed Balb/c 3T3 cells. Curcumin caused DNA damage in transformed Balb/c 3T3 cells. Curcumin may play a protective role in sodium arsenite-induced toxicity.


Abstract Arsenic is a toxic substance that spreads widely around the environment and accumulates as metalloid in the earth's crust. Arsenic and its derivatives are found in drinking water, nutrients, soil, and air. Exposure to arsenic is associated with lung, blood, skin cancer and various lesions. Curcumin is a polyphenolic compound derived from Curcuma longa (turmeric) rhizome and is one of the main curcuminoids. Curcumin is known to be antioxidant, antibacterial, anti-inflammatory, analgesic effects. This study aimed to investigate the potential of sodium arsenite to transform embryonic fibroblast cells and to evaluate the cytotoxic and genotoxic effects of curcumin in neoplastic transformed cells. Neoplastic cells transformation was induced by sodium arsenite in Balb/c 3T3 cells at the end of 32 days. After transformation assay, the transformed cells were treated with various concentration of curcumin to evaluate cell viability, lactate dehydrogenase activity and DNA damage for 24h. The results revealed that curcumin decreased cell viability and increased the activity of lactate dehydrogenase enzyme in neoplastic transformed Balb/c 3T3 cells. In conclusion, the results demonstrated that curcumin has an anticancer effect on neoplastic transformed Balb/c 3T3 cells by causing DNA damage.


Assuntos
Animais , Camundongos , Arsênio/toxicidade , Dano ao DNA , Transformação Celular Neoplásica , Curcumina/farmacologia , Fibroblastos/efeitos dos fármacos , Células 3T3 BALB , Fibroblastos/patologia
8.
An. bras. dermatol ; 94(4): 462-469, July-Aug. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1038307

RESUMO

Abstract: Cutaneous mucinoses are a heterogeneous group of dermatoses in which excess deposition of mucin in the dermis gives the skin a waxy appearance, with papules and plaques that can vary from self-healing mucinosis to even disrupting the normal shape of a patient's face, conferring a leonine facies, or be part of life threatening diseases like scleromyxedema. This review will describe the most recent classification on lichen myxedematosus in the generalized (scleromyxedema) and the localized forms, as well as the different organ systems involved in scleromyxedema, diagnostic workup, current management, and prognosis.


Assuntos
Humanos , Dermatopatias/diagnóstico , Dermatopatias/patologia , Escleromixedema/diagnóstico , Escleromixedema/patologia , Pele/patologia , Dermatopatias/classificação , Dermatopatias/terapia , Escleromixedema/classificação , Escleromixedema/terapia , Fibroblastos/patologia , Mucinas
9.
Acta cir. bras ; 34(2): e201900202, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-989055

RESUMO

Abstract Purpose: To evaluate the hyaluronic acid (HA) inflammatory reaction, fibroblasts, fibrosis and duration of effect in the dorsal region of tobacco-exposed rats. Methods: Ten Wistar rats were divided into two groups: tobacco-exposed-group (TEG;n=5) and air-control-group (CG;n=5). The TEG animals were tobacco-exposed twice a day, 30-minutes/session, during 60 days. After this period, all animals received 0.1 mL HA subcutaneous injection in the dorsal area. The volume of HA was measured immediately after HA injection and weekly using a hand-caliper in nine weeks. After this period, all the animals were euthanized, and a specimen of was collected to evaluate inflammatory cells, fibroblasts, and fibrosis by HE. Results: This study showed a higher inflammatory reaction in TEG than CG: inflammatory cell-count (CG: 1.07±0.9; TEG: 8.61±0.36, p<0.001); fibroblast count (CG: 2.92±0.17; TEG: 19.14±0.62, p<0.001), and fibrosis quantification (CG: 2.0; TEG: 3.75, p<0.001). The analysis of the HA volume in nine weeks in the dorsal region did not show a difference between groups (p=0.39). Conclusions: This study suggested that the HA injection in the TEG caused an increase in inflammatory cell count, fibroblast, and fibrosis quantification when compared to the CG. There was no difference in the duration of effect of HA between the groups.


Assuntos
Animais , Masculino , Ratos , Nicotiana/efeitos adversos , Exposição por Inalação/efeitos adversos , Viscossuplementos/efeitos adversos , Fibroblastos/efeitos dos fármacos , Ácido Hialurônico/efeitos adversos , Inflamação/patologia , Fatores de Tempo , Fibrose , Ratos Wistar , Modelos Animais de Doenças , Espaço Epidural/efeitos dos fármacos , Espaço Epidural/patologia , Fibroblastos/patologia , Inflamação/induzido quimicamente
10.
Acta cir. bras ; 33(8): 703-712, Aug. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-949375

RESUMO

Abstract Purpose: To assess the action of vitamin C on the expression of 84 oxidative stress related-genes in cultured skin fibroblasts from burn patients. Methods: Skin samples were obtained from ten burn patients. Human primary fibroblasts were isolated and cultured to be distributed into 2 groups: TF (n = 10, fibroblasts treated with vitamin C) and UF (n = 10, untreated fibroblasts). Gene expression analysis using quantitative polymerase chain reaction array was performed for comparisons between groups. Results: The comparison revealed 10 upregulated genes as follows: arachidonate 12-lipoxygenase (ALOX12), 24-dehydrocholesterol reductase (DHCR24), dual oxidase 1 (DUOX1), glutathione peroxidase 2 (GPX2), glutathione peroxidase 5 (GPX5), microsomal glutathione S-transferase 3 (MGST3), peroxiredoxin 4 (PRDX4), phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 (P-REX1), prostaglandin-endoperoxide synthase 1 (PTGS1), and ring finger protein 7 (RNF7). Conclusion: Cultured fibroblasts obtained from burn patients and treated with vitamin C resulted in 10 differentially expressed genes, all overexpressed, with DUOX1, GPX5, GPX2 and PTGS1 being of most interest.


Assuntos
Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Ácido Ascórbico/farmacologia , Queimaduras/patologia , Expressão Gênica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Valores de Referência , Pele/patologia , Araquidonato 12-Lipoxigenase/análise , Araquidonato 12-Lipoxigenase/efeitos dos fármacos , Queimaduras/tratamento farmacológico , Células Cultivadas , Estudos Transversais , Estatísticas não Paramétricas , Ubiquitina-Proteína Ligases/análise , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/análise , Ciclo-Oxigenase 1/análise , Ciclo-Oxigenase 1/efeitos dos fármacos , Peroxirredoxinas/análise , Reação em Cadeia da Polimerase em Tempo Real , Oxidases Duais/análise , Oxidases Duais/efeitos dos fármacos , Glutationa Peroxidase/análise , Glutationa Peroxidase/efeitos dos fármacos
11.
An. bras. dermatol ; 93(2): 268-270, Mar.-Apr. 2018. graf
Artigo em Inglês | LILACS | ID: biblio-887174

RESUMO

Abstract: This study describes a case of a 19-year-old patient with seven asymptomatic lesions on the chest, measuring between 0.5 to 1cm in diameter, with no history of trauma in the region. The immunohistochemical evaluation was positive for vimentin and smooth muscle actin, determining Dermatomyofibroma as definitive diagnosis. Dermatomyofibroma is a benign skin tumor, with a myofibroblastic origin, prevalent in young women. It usually presents as a single lesion, with very few reports of multiple lesions.


Assuntos
Humanos , Feminino , Adulto Jovem , Neoplasias Cutâneas/patologia , Miofibroma/patologia , Biópsia , Imuno-Histoquímica , Cicatriz Hipertrófica/patologia , Fibroblastos/patologia
12.
Acta cir. bras ; 33(2): 144-155, Feb. 2018. graf
Artigo em Inglês | LILACS | ID: biblio-886256

RESUMO

Abstract Purpose: To evaluate the efficacy of the application of the human amniotic membrane (HAM) on the inflammatory process, fibroblast proliferation, formation of collagenand reduction of skin wound areas in rats. Methods: Thirty six rats were submitted to a surgical injury induction and divided into two groups (n = 18): group C (control) and T (treated with the HAM). The macroscopic evolution in the wound area and the histological characteristics of the skin samples were evaluated. Results: The regression of the wound area was greater in group T. The histological analysis revealed a significant reduction (p < 0.05) in the inflammatory infiltrate in group T at all experimental periods compared with that in the control group. Furthermore, the group T presented a significant increase in the proliferation of fibroblasts at 14 and 21 days compared with group C (p < 0.05). Regarding the deposition of mature collagen fibers, there was an increase in the replacement of type III collagen by type I collagen in group T (p < 0.05). Conclusion: Treatment with the HAM reduced the healing time as well as the inflammatory responses, increased the proliferation of fibroblasts, and induced a higher concentration of mature collagen fibers.


Assuntos
Humanos , Animais , Masculino , Ratos , Pele/lesões , Cicatrização/fisiologia , Curativos Biológicos , Colágeno/farmacologia , Âmnio/transplante , Pele/patologia , Cicatrização/efeitos dos fármacos , Distribuição Aleatória , Ratos Wistar , Colágeno Tipo I/metabolismo , Colágeno Tipo I/farmacologia , Colágeno Tipo III/metabolismo , Colágeno Tipo III/farmacologia , Modelos Animais de Doenças , Fibroblastos/metabolismo , Fibroblastos/patologia , Âmnio/química , Inflamação/metabolismo
13.
Pesqui. bras. odontopediatria clín. integr ; 18(1): 4085, 15/01/2018. tab, ilus
Artigo em Inglês | LILACS, BBO | ID: biblio-966895

RESUMO

Objective: To compare the potency of fibroblast cells proliferation in 12.5% and 25% Culture Media Conditioned Warton's Jelly (CMCWJ) and Advanced Platelet Rich Fibrin (A-PRF) cultured medium. Material and Methods: Fibroblast cells were divided into five groups: Group I (Control Group): serum-starved fibroblast without any treatment as a negative control; Group II: fibrolast that supplemented in 12.5% CMCWJ medium; Group III: fibrolast that supplemented 12.5% A-PRF medium; Group IV: fibrolast that supplemented 25% CMCWJ medium, and Group V: fibrolast that supplemented 25% A-PRF medium. The fibroblasts proliferation was counted by an automated cell counter. Statistical analysis was performed using One-way ANOVA and Post hoc Tamhane test was conducted to analyze the potential fibroblast proliferation differences in different concentration of CMCWJ and A-PRF group. Results: There were no significant differences in the fibroblast cell proliferation between GI and GIV, GII and GIV, GII and GIII, GII and GV, also GIV and GV. There were significant differences between GI and GII, GI and GIII, GI and GV, also GIII and GIV. Conclusion: The 12.5% CMCWJ group, 12.5% A-PRF group and 25% A-PRF group has excellent potential ability of fibroblast cells proliferation, meanwhile 25% CMCWJ group has the lowest mean potency of fibroblast cells proliferation compared to other groups. The 12.5% A-PRF Group has the highest mean of fibroblast cell proliferation amongst other groups.


Assuntos
Proliferação de Células , Geleia de Wharton/patologia , Fibroblastos/patologia , Fibrina Rica em Plaquetas , Indonésia
14.
Asian Journal of Andrology ; (6): 372-378, 2018.
Artigo em Inglês | WPRIM | ID: wpr-1009590

RESUMO

We evaluated whether LIM-kinase 2 inhibitor (LIMK2i) could improve erectile function by suppressing corporal fibrosis through the normalization of the Rho-associated coiled-coil protein kinase 1 (ROCK1)/LIMK2/Cofilin pathway in a rat model of cavernous nerve crush injury (CNCI). Sixty 11-week-old male Sprague-Dawley rats were divided equally into five groups: sham surgery (S), CNCI (I), and CNCI treated with low-dose (L), medium-dose (M), and high-dose (H) LIMK2i. The L, M, and H groups were treated with a daily intraperitoneal injection of LIMK2i (2.5, 5.0, and 10.0 mg kg-1 body weight, respectively) for 1 week after surgery. The erectile response was assessed using electrostimulation at 1 week, postoperatively. Penile tissues were processed for Masson's trichrome staining, double immunofluorescence, and Western blot assay. Erectile responses in the H group improved compared with the I group, while the M group showed only partial improvement. A significantly decreased smooth muscle/collagen ratio and an increased content of fibroblasts positive for phospho-LIMK2 were noted in the I group. The M and H groups revealed significant improvements in histological alterations and the dysregulated LIMK2/Cofilin pathway, except for LIMK2 phosphorylation in the M group. The inhibition of LIMK2 did not affect the ROCK1 protein expression. The content of fibroblasts positive for phospho-LIMK2 in the H group returned to the level found in the S group, whereas it did not in the M group. However, the L group did not exhibit such improvements. Our data suggest that the inhibition of LIMK2, particularly with administration of 10.0 mg kg-1 body weight LIMK2i, can improve corporal fibrosis and erectile function by normalizing the LIMK2/Cofilin pathway.


Assuntos
Animais , Masculino , Ratos , Cofilina 1/metabolismo , Estimulação Elétrica , Disfunção Erétil/etiologia , Fibroblastos/patologia , Fibrose/tratamento farmacológico , Quinases Lim/antagonistas & inibidores , Doenças do Pênis/tratamento farmacológico , Pênis/inervação , Traumatismos dos Nervos Periféricos/patologia , Fosforilação , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Quinases Associadas a rho/genética
15.
Bol. méd. Hosp. Infant. Méx ; 74(3): 175-180, May.-Jun. 2017. graf
Artigo em Inglês | LILACS | ID: biblio-888613

RESUMO

Abstract: Background: Mitochondriopathies are multisystem diseases affecting the oxidative phosphorylation (OXPHOS) system. Skin fibroblasts are a good model for the study of these diseases. Fibroblasts with a complex IV mitochondriopathy were used to determine the molecular mechanism and the main affected functions in this disease. Methods: Skin fibroblast were grown to assure disease phenotype. Mitochondria were isolated from these cells and their proteome extracted for protein identification. Identified proteins were validated with the MitoMiner database. Results: Disease phenotype was corroborated on skin fibroblasts, which presented a complex IV defect. The mitochondrial proteome of these cells showed that the most affected proteins belonged to the OXPHOS system, mainly to the complexes that form supercomplexes or respirosomes (I, III, IV, and V). Defects in complex IV seemed to be due to assembly issues, which might prevent supercomplexes formation and efficient substrate channeling. It was also found that this mitochondriopathy affects other processes that are related to DNA genetic information flow (replication, transcription, and translation) as well as beta oxidation and tricarboxylic acid cycle. Conclusions: These data, as a whole, could be used for the better stratification of these diseases, as well as to optimize management and treatment options.


Resumen: Introducción: Las mitocondriopatías son enfermedades multisistémicas que afectan el funcionamiento de la fosforilación oxidativa (OXPHOS). Un buen modelo de estudio para estas enfermedades es el cultivo primario de fibroblastos. En este trabajo se utilizaron fibroblastos con mitocondriopatía del complejo IV para determinar cuáles son las principales funciones afectadas en esta enfermedad. Métodos: Se realizaron cultivos primarios de fibroblastos para corroborar el fenotipo de la enfermedad. Las mitocondrias se aislaron de estas células y se extrajo su proteoma para su identificación. Las proteínas identificadas se validaron con la base de datos de MitoMiner. Resultados: Los fibroblastos conservaron el fenotipo de la enfermedad que incluye un defecto del complejo IV. El proteoma mitocondrial de estas células mostró que las proteínas más afectadas pertenecen al sistema de OXPHOS, principalmente los complejos que forman supercomplejos o respirosomas (I, III, IV y V). El defecto en el complejo IV al parecer se debió a problemas de ensamblaje que pueden evitar la formación de los supercomplejos y la eficiente canalización de sustratos. También se observó que esta mitocondriopatía afecta otros procesos relacionados con el flujo de información genética del DNA (replicación, transcripción y traducción), así como con la beta oxidación y el ciclo de los ácidos tricarboxílicos (TCA). Conclusiones: En conjunto, estos datos podrían utilizarse para una mejor clasificación de estas enfermedades, así como para la optimización de las opciones de manejo y tratamiento.


Assuntos
Humanos , Deficiência de Citocromo-c Oxidase/patologia , Proteômica/métodos , Fibroblastos/patologia , Mitocôndrias/patologia , Fosforilação Oxidativa , DNA/genética , Proteínas/metabolismo , Células Cultivadas , Ciclo do Ácido Cítrico/fisiologia
16.
An. bras. dermatol ; 91(6): 776-780, Nov.-Dec. 2016.
Artigo em Inglês | LILACS | ID: biblio-837986

RESUMO

Abstract The transforming growth factor-beta 1 (TGFβ1) promotes fibrosis, differentiating epithelial cells and quiescent fibroblasts into myofibroblasts and increasing expression of extracellular matrix. Recent investigations have shown that PPAR (peroxisome proliferator-activated receptor*) is a negative regulator of fibrotic events induced by TGFβ1. Dehydroepiandrosterone (DHEA) is an immunomodulatory hormone essential for PPAR functions, and is reduced in some processes characterized by fibrosis. Although scarring alopecia characteristically develops in the female biological period in which occurs decreased production of DHEA, there are no data in the literature relating its reduction to fibrogenic process of this condition. This article aims to review the fibrogenic activity of TGFβ1, its control by PPAR and its relation with DHEA in the frontal fibrosing alopecia.


Assuntos
Humanos , Feminino , Desidroepiandrosterona/fisiologia , Alopecia/fisiopatologia , Alopecia/patologia , Fibrose , PPAR gama/fisiologia , Alopecia/etiologia , Alopecia/terapia , Fator de Crescimento Transformador beta1/fisiologia , Fibroblastos/fisiologia , Fibroblastos/patologia , Líquen Plano/patologia
17.
An. bras. dermatol ; 91(6): 842-843, Nov.-Dec. 2016. graf
Artigo em Inglês | LILACS | ID: biblio-837997

RESUMO

Abstract Scleromyxedema or lichen myxedematosus is a rare papular mucinosis of chronic and progressive course and unknown etiology. It is commonly associated with monoclonal gammopathy and may show extracutaneous manifestations, affecting the heart, lung, kidney, and nerves. The diagnosis is based on four criteria: generalized papular and sclerodermoid lesions; mucin deposition, fibroblast proliferation, and fibrosis in the histopathology; monoclonal gammopathy; and no thyroid disorders. This article reports the case of a scleromyxedema patient with a recent history of acute myocardial infarction and monoclonal gammopathy.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Derme/patologia , Escleromixedema/patologia , Proliferação de Células , Fibroblastos/patologia , Mucinas
18.
Int. j. morphol ; 34(3): 945-949, Sept. 2016. ilus
Artigo em Espanhol | LILACS | ID: biblio-828967

RESUMO

La reacción y reparación de la dentina depende del número de células presentes en la pulpa, dentro de éstas fibroblastos. Los métodos diseñados para obtener una estimación fiable de la cantidad de elementos celulares de la pulpa han sido subjetivos y sesgados, sobre todo al evaluar los cambios cuantitativos y potencial capacidad reparadora en presencia de caries. El objetivo fue estimar y comparar cuantitativamente las densidades de número, volumen y superficie de fibroblastos en pulpas sanas y con diagnóstico de pulpitis reversible producto de caries en dientes humanos jóvenes. Se utilizaron dientes premolares humanos obtenidos de exodoncias, divididos en un grupo sano y cariado, los cuales fueron fijados y posteriormente descalcificados con ácido nítrico al 5 %. Siguiendo el protocolo del orientator se obtuvieron 5 secciones de 5 µm teñidas por H-E de cada diente. Se aplicó el recuento estereológico de los fibroblastos pulpares (FP) con el test multipropósito M42. Se estimaron las densidades de número (Nv), volumen (Vv) y superficie (Sv), y calcularon las Medias (±DE) por diente, y Medias (±EE) por grupo. Las diferencias entre grupos se analizaron mediante la prueba T, con un valor p 0,05 de significación estadística. En dientes sanos, la Media (±EE) para Nv de FP fue 0,393 x 105/mm3 (±0,020x105/mm3), para Vv 15,467 % (±1,334 %) y para Sv 16,330 mm2/mm3 (±1,274 mm2/mm3). En dientes cariados, la Nv fue 0,447 x 105/mm3 (±0,019x105/mm3), la Vv 20,171 % (±1,213 %) y la Sv 20,150 mm2/mm3 (±1,447 mm2/mm3). Al comparar las Nv, los FP del grupo con caries aumentaron significativamente (p= 0,047), al igual que la Vv (p= 0,0105) y Sv (p= 0,013). Existe un aumento del número de FP en los dientes con pulpitis reversible, lo que condicionaría su capacidad de respuesta. La metodología empleada puede ser aplicable para determinar el comportamiento pulpar y cuantificar variables de respuesta odontoblástica en tratamientos restauradores atraumáticos de manera imparcial y reproducible.


Dentine reaction and repair depends on the number of cells present in the pulp, within these fibroblasts. The methods designed to obtain a reliable estimate of the amount of cellular elements of the dental pulp have been subjective and biased, especially when evaluating quantitative changes and potential reparative capacity in the presence of caries. The aim of this study was to estimate and quantitatively compare with stereological tools, number, density, volume and surface of fibroblasts in healthy teeth and reversible pulpitis diagnosis due to caries. We obtained premolar teeth from human tooth extractions, divided into healthy and carious groups, which were fixed and decalcified with 5 % nitric. Following the orientator protocol we obtained 5 sections of 5 µm from each tooth which were stained by H-E. The stereological counting of pulp fibroblasts (FP) with M42 multipurpose test was applied. Number densities (Nv), volume (Vv) and surface (Sv) were estimated, and calculated the means (±SD) for a tooth, and Mean (±SE) per group. Differences between groups were analyzed by t-test, p 0.05 a statistically significant value. In healthy teeth, the mean (±SE) for Nv FP was 0.393x105/mm3 (±0.020x105/mm3), Vv 15.467 % (±1.334 %) and Sv 16.330 mm2/mm3 (±1.274 mm2/mm3). In decayed teeth, it was 0.447x105 Nv/mm3 (±0.019x105/mm3), the Vv 20.171 % (±1.213 %) and Sv 20.150 mm2/mm3 (± 1.447 mm2/mm3). Comparing Nv, the FP carious group increased significantly (p =0.047), as Vv (p =0.0105) and Sv (p =0.013). There is an increased number of FP teeth with reversible pulpitis, which would determine their responsiveness. The methodology can be applied to determine the pulp behavior and odontoblast quantify response variables in impartially and reproducible atraumatic restorative treatments.


Assuntos
Humanos , Adolescente , Adulto , Polpa Dentária/anatomia & histologia , Fibroblastos/patologia , Fibroblastos/fisiologia , Pulpite/patologia , Técnicas Estereotáxicas
19.
Acta cir. bras ; 31(7): 463-471, tab, graf
Artigo em Inglês | LILACS | ID: lil-787263

RESUMO

ABSTRACT PURPOSE: To evaluate the effects of low intensity ultrasound on the healing process of third degree burn wounds in experimentally induced diabetic Wistar rats. METHODS: One hundred rats were divided into: control group; non-diabetic treated group; diabetic control group; diabetic treated group. The therapy was performed with a 3MHz ultrasound application, pulsed emission at 100Hz frequency, modulated at 20% with a dosage of 0.5W/cm2 during three minutes throughout 30 days. The surgical debridement of the wound was performed once at day 2. The wounds were morphometrically, macroscopically and microscopically evaluated at 3, 7, 14, 21 and 30 days. RESULTS: The wound contraction and collagen quantification were higher in all treated groups. Macroscopically, necrosis was higher in the diabetic control group. Granulation tissue was higher in treated groups during the proliferative and remodeling phase. Microscopically, there were greater mononuclear inflammatory infiltration, angiogenesis and fibroblast quantification in treated groups during the proliferative and remodeling phases. CONCLUSIONS: therapeutic ultrasound is beneficial in the inflammatory and proliferative phases of the healing process because it controlled the necrotic tissue, increased the granulation tissue and wound contraction. However in the remodeling phase it is not beneficial because of the continued angiogenesis and a mononuclear inflammatory infiltration.


Assuntos
Animais , Feminino , Pele/lesões , Terapia por Ultrassom/métodos , Cicatrização/fisiologia , Queimaduras/terapia , Indutores da Angiogênese/uso terapêutico , Diabetes Mellitus Experimental , Queimaduras/patologia , Colágeno/análise , Ratos Wistar , Modelos Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/terapia , Fibroblastos/patologia , Tecido de Granulação , Necrose/patologia , Necrose/reabilitação
20.
Acta cir. bras ; 30(12): 806-811, Dec. 2015. graf
Artigo em Inglês | LILACS | ID: lil-769498

RESUMO

ABSTRACT PURPOSE: To analyze the effects of the low-level laser therapy in the acute myositis induced in rats. METHODS: Twelve rats were subjected to bilateral ovariectomy for inducing osteoporosis. After surgery, they were divided into two groups: Ovariectomy-control group (G1, n=6), receiving 0.5 ml distilled water by gavage for 30 days, and Ovariectomy plus mastruz group (G2, n=6), receiving 0.5 ml of the hydroalcoholic extract of mastruz at 10% concentration (50mg) daily, for the same period. Then, the blood of the animals was collected for further biochemical analysis (liver function) and tibia and liver were removed for histological and histomorphometric analyses. RESULTS: In the MT group there was a statistic significant decrease in the number of inflammatory cells, related to the MI group (p<0.05), increase in the fibroblastic proliferation, when compared to groups C and MI related to MT group (p<0.01) and statistic significant edema regression (p=0.0400) in the MT group CONCLUSION: The low-level laser therapy was efficient in the reduction of the inflammatory process, increase of the fibroblastic proliferation and the reduction of the edema.


Assuntos
Animais , Masculino , Edema/radioterapia , Lasers Semicondutores/uso terapêutico , Terapia com Luz de Baixa Intensidade/métodos , Miosite/radioterapia , Doença Aguda , Fibroblastos/patologia , Modelos Animais , Músculo Esquelético/patologia , Miosite/induzido quimicamente , Doses de Radiação , Distribuição Aleatória , Ratos Wistar
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