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Fractional carbon dioxide (CO2) laser has been used with conventional treatments for vitiligo, demonstrating more effectiveness compared with conventional treatments alone. Especially, fractional CO2 laser combined with narrow-band ultraviolet B (NB-UVB) was shown to induce more improvement compared with NB-UVB monotherapy for treating stable non-segmental vitiligo. However, the effectiveness of fractional CO2 laser plus NB-UVB for the treatment of non-segmental vitiligo remains controversial. Therefore, this study aimed to confirm the safety and efficacy of fractional CO2 laser combined with NB-UVB compared with NB-UVB monotherapy in stable non-segmental vitiligo. We searched the data from different databases, including Cochrane, Embase, and PubMed up to January 2020. Four randomized controlled trials (RCTs) for comparison between fractional CO2 laser plus NB-UVB and NB-UVB monotherapy in patients with stable non-segmental vitiligo were included. We performed meta-analyses for repigmentation improvement and patient satisfaction as well as subgroup analyses based on acral or non-acral vitiligo, according to the PRISMA guidelines. The combination treatment showed more superior results than NB-UVB monotherapy (≥ 75% repigmentation, RR 4.60, 95% CI 1.19-17.74; ≥ 50% repigmentation, RR 2.24, 95% CI 0.45-11.17; < 25% repigmentation, RR 0.81, 95% CI 0.60-1.08). Also, fractional CO2 laser plus NB-UVB significantly improved acral and non-acral vitiligo compared with NB-UVB monotherapy (standard mean difference (SMD) 1.24, 95% CI 0.66-1.82; SMD 1.14, 95% CI 0.67-1.60, respectively), while it increased markedly patient satisfaction compared with NB-UVB monotherapy (SMD 1.12, 95% CI 0.66-1.58). Collectively, this meta-analysis suggested that fractional CO2 laser combined with NB-UVB might be more effective for treating non-segmental vitiligo than NB-UVB monotherapy.
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Lasers de Gás/uso terapêutico , Terapia Ultravioleta , Vitiligo/cirurgia , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Satisfação do Paciente , Pigmentação/efeitos da radiação , Viés de Publicação , RiscoRESUMO
Arctigenin, a mitochondrial complex I inhibitor, has been identified as a potential anti-tumor agent, but the involved mechanism still remains elusive. Herein, we studied the underlying mechanism(s) of action of arctigenin on acidity-tolerant prostate cancer PC-3AcT cells in the lactic acid-containing medium. At concentration showing no toxicity on normal prostate epithelial RWPE-1 and HPrEC cells, arctigenin alone or in combination with docetaxel induced significant cytotoxicity in PC-3AcT cells compared to parental PC-3 cells. With arctigenin treatment, reactive oxygen species (ROS) levels, annexin V-PE positive fractions, sub-G0/G1 peak in cell cycle analysis, mitochondrial membrane depolarization, and cell communication network factor 1 (CCN1) levels were increased, while cellular ATP content and phospho (p)-Akt level were decreased. Pretreatment with ROS scavenger N-acetylcysteine effectively reversed the series of phenomena caused by arctigenin, suggesting that ROS served as upstream molecules of arctigenin-driven cytotoxicity. Meanwhile, arctigenin increased the levels of p-receptor-interacting serine/threonine-protein kinase 3 (p-RIP3) and p-mixed lineage kinase domain-like pseudokinase (p-MLKL) as necroptosis mediators, and pretreatment with necroptosis inhibitor necrostatin-1 restored their levels and cell viability. Treatment of spheroids with arctigenin resulted in necroptotic cell death, which was prevented by N-acetylcysteine. The siRNA-based knockdown of CCN1 suppressed the levels of MLKL, B-cell lymphoma 2 (Bcl-2), and induced myeloid leukemia cell differentiation (Mcl-1) with increased cleavage of Bcl-2-associated X (Bax) and caspase-3. Collectively, these results provide new insights into the molecular mechanisms underlying arctigenin-induced cytotoxicity, and support arctigenin as a potential therapeutic agent for targeting non-Warburg phenotype through induction of necroptosis via ROS-mediated mitochondrial damage and CCN1 upregulation.
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Furanos/farmacologia , Ácido Láctico/farmacologia , Lignanas/farmacologia , Mitocôndrias/metabolismo , Neoplasias da Próstata/metabolismo , Regulação para Cima , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura/química , Ciclina D1 , Docetaxel/farmacologia , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Necroptose , Células PC-3 , Neoplasias da Próstata/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismoRESUMO
Scleromyxedema is a rare connective tissue disorder characterized by a generalized lichenoid eruption and sclerodermoid induration with histologic features of dermal mucin deposition. A 44-year-old man presented with a 3-year history of generalized progressive skin thickening and sclerosis. He had diffuse skin-colored to erythematous firm papules coalescing into indurated plaques over his whole body. He had been diagnosed with scleromyxedema from a skin biopsy with monoclonal gammopathy of undetermined significance (MGUS) at another tertiary hospital 3 years earlier. He had been treated with systemic corticosteroids and methotrexate, but his systemic symptoms (dyspnea, dysphagia, skin swelling, and induration) had worsened over the past year, so he visited our clinic seeking further evaluation and management. The patient received high-dose intravenous immunoglobulin (IVIG) therapy once a month in combination with systemic corticosteroids. After three courses of IVIG, his cutaneous symptoms and dyspnea had improved dramatically. Herein we report a case of scleromyxedema with systemic involvement with significant improvement following IVIG therapy.
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Erupções Liquenoides , Escleromixedema , Adulto , Biópsia , Humanos , Imunoglobulinas Intravenosas , Masculino , Escleromixedema/diagnóstico , Escleromixedema/tratamento farmacológico , PeleRESUMO
BACKGROUND: Acne vulgaris is a common skin disease primarily affecting young adults. Given that the internet has become a major source of health information, especially among the young, the internet is a powerful tool of communication and has a significant influence on patients. OBJECTIVE: This study aimed to clarify the features of patients' interest in and evaluate the quality of information about acne vulgaris on the internet. METHODS: We compared the search volumes on acne vulgaris with those of other dermatological diseases using Google Trends from January 2004 to August 2019. We also determined the search volumes for relevant keywords of acne vulgaris on Google and Naver and evaluated the quality of answers to the queries in KnowledgeiN. RESULTS: The regression analysis of Google Trends data demonstrated that the patients' interest in acne vulgaris was higher than that for other dermatological diseases, such as atopic dermatitis (ß=-20.33, 95% CI -22.27 to -18.39, P<.001) and urticaria (ß=-27.09, 95% CI -29.03 to -25.15, P<.001) and has increased yearly (ß=2.38, 95% CI 2.05 to 2.71, P<.001). The search volume for acne vulgaris was significantly higher in the summer than in the spring (ß=-5.04, 95% CI -9.21 to -0.88, P=.018) and on weekends than on weekdays (ß=-6.68, 95% CI -13.18 to -0.18, P=.044). The most frequently searched relevant keywords with "acne vulgaris" and "cause" were "stress," "food," and "cosmetics." Among food, the 2 highest acne vulgaris-related keywords were milk and wheat in Naver and coffee and ramen in Google. The queries in Naver KnowledgeiN were mostly answered by a Korean traditional medicine doctor (53.4%) or the public (33.6%), but only 12.0% by dermatologists. CONCLUSIONS: Physicians should be aware of patients' interest in and beliefs about acne vulgaris to provide the best patient education and care, both online and in the clinic.
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Acne Vulgar/epidemiologia , Ferramenta de Busca/métodos , Feminino , Humanos , Internet , MasculinoRESUMO
Apigenin, a naturally occurring flavonoid, is known to exhibit significant anticancer activity. This study was designed to determine the effects of apigenin on two malignant mesothelioma cell lines, MSTO-211H and H2452, and to explore the underlying mechanism(s). Apigenin significantly inhibited cell viability with a concomitant increase in intracellular reactive oxygen species (ROS) and caused the loss of mitochondrial membrane potential (Δð¿m), and ATP depletion, resulting in apoptosis and necroptosis in monolayer cell culture. Apigenin upregulated DNA damage response proteins, including the DNA double strand break marker phospho (p)- histone H2A.X. and caused a transition delay at the G2/M phase of cell cycle. Western blot analysis showed that apigenin treatment upregulated protein levels of cleaved caspase-3, cleaved PARP, p-MLKL, and p-RIP3 along with an increased Bax/Bcl-2 ratio. ATP supplementation restored cell viability and levels of DNA damage-, apoptosisand necroptosis-related proteins that apigenin caused. In addition, N-acetylcysteine reduced ROS production and improved Δð¿m loss and cell death that were caused by apigenin. In a 3D spheroid culture model, ROS-dependent necroptosis was found to be a mechanism involved in the anti-cancer activity of apigenin against malignant mesothelioma cells. Taken together, our findings suggest that apigenin can induce ROS-dependent necroptotic cell death due to ATP depletion through mitochondrial dysfunction. This study provides us a possible mechanism underlying why apigenin could be used as a therapeutic candidate for treating malignant mesothelioma.
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BACKGROUND: Reduced cell spreading is a prominent feature of aged dermal fibroblasts in human skin in vivo. Mitochondrial DNA (mtDNA) common deletion has been reported to play a role in the human aging process, however the relationship between age-related reduced cell spreading and mtDNA common deletion has not yet been reported. RESULTS: To examine mtDNA common deletion in the dermis of aged human skin, the epidermis was removed from full-thickness human skin samples using cryostat. mtDNA common deletion was significantly elevated in the dermis of both naturally aged and photoaged human skin in vivo. To examine the relationship between age-related reduced cell spreading and mtDNA common deletion, we modulated the shape of dermal fibroblasts by disrupting the actin cytoskeleton. Reduced cell spreading was associated with a higher level of mtDNA common deletion and was also accompanied by elevated levels of endogenous reactive oxygen species (ROS). Boosting cellular antioxidant capacity by using antioxidants was found to be protective against mtDNA common deletion associated with reduced cell spreading. CONCLUSION: mtDNA common deletion is highly prevalent in the dermis of both naturally aged and photoaged human skin in vivo. mtDNA common deletion in response to reduced cell spreading is mediated, at least in part, by elevated oxidative stress in human dermal fibroblasts. These data extend current understanding of the mitochondrial theory of aging by identifying the connection between mtDNA common deletion and age-related reduction of cell spreading.
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Envelhecimento/metabolismo , DNA Mitocondrial/metabolismo , Derme/metabolismo , Fibroblastos/metabolismo , Estresse Oxidativo , Deleção de Sequência , Envelhecimento da Pele , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Envelhecimento/patologia , DNA Mitocondrial/genética , Derme/patologia , Fibroblastos/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A high dependence on aerobic glycolysis, known as the Warburg effect, is one of the metabolic features exhibited by tumor cells. Therefore, targeting glycolysis is becoming a very promising strategy for the development of anticancer drugs. In the present study, it was investigated whether preadaptation of malignant mesothelioma (MM) cells to an acidic environment was associated with a metabolic shift to the Warburg phenotype in energy production, and whether apigenin targets acidosisdriven metabolic reprogramming. Cell viability, glycolytic activity, Annexin VPE binding activity, reactive oxygen species (ROS) levels, mitochondrial membrane potential, ATP content, western blot analysis and spheroid viability were assessed in the present study. MM cells preadapted to lactic acid were resistant to the anticancer drug gemcitabine, increased Akt activation, downregulated p53 expression, and upregulated ratelimiting enzymes in glucose metabolism compared with their parental cells. Apigenin treatment increased cytotoxicity, Akt inactivation and p53 upregulation. Apigenin also reduced glucose uptake along with downregulation of key regulatory enzymes in glycolysis, increased ROS levels with loss of mitochondrial membrane potential, and downregulated the levels of complexes I, III and IV in the mitochondrial electron transport chain with intracellular ATP depletion, resulting in upregulation of molecules mediating apoptosis and necroptosis. Apigenininduced alterations of cellular responses were similar to those of Akt inactivation by Ly294002. Overall, the present results provide mechanistic evidence supporting the antiglycolytic and cytotoxic role of apigenin via inhibition of the PI3K/Akt signaling pathway and p53 upregulation.
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Mesotelioma Maligno , Mesotelioma , Humanos , Regulação para Cima , Proteínas Proto-Oncogênicas c-akt/metabolismo , Apigenina/farmacologia , Apigenina/uso terapêutico , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Necroptose , Mesotelioma/tratamento farmacológico , Mesotelioma/genética , Mesotelioma/patologia , Apoptose , Glicólise , Trifosfato de Adenosina/metabolismoRESUMO
BACKGROUND: Recent studies suggest that MEK1/2 inhibitors, including binimetinib, significantly improve malignant melanoma (MM) patient survival. Growing evidence suggests that phytochemicals, especially curcumin, can overcome drug resistance in cancer cells through a variety of mechanisms. OBJECTIVE: This study aims to examine curcumin's efficacy in vitro combined with binimetinib in human MM cells. METHODS: We used 2D monolayer and 3D spheroid human epidermal melanocyte culture models, HEMn-MP (human epidermal melanocytes, neonatal, moderately pigmented), and two human MM cell lines, G361 and SK-MEL-2, to evaluate cell viability, proliferation, migration, death, and reactive oxygen species (ROS) production following single therapy treatment, with either curcumin or binimetinib, or a combination of both. RESULTS: Compared to MM cells treated with single therapy, those with combination therapy showed significantly decreased cell viability and increased ROS production. We observed apoptosis following both single and combination therapies. However only those who had had combination therapy had necroptosis. CONCLUSION: Collectively, our data demonstrates that curcumin exerts significant synergistic anticancer effects on MM cells by inducing ROS and necroptosis when combined with binimetinib. Therefore, a strategy of adding curcumin to conventional anticancer agents holds promise for treating MM.
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BACKGROUND: Melanoma is one of the most aggressive and metastatic skin cancers. Although overexpression of Dock180 and Elmo1 has been identified in various cancers, including glioma, ovarian cancer, and breast cancer, their expression and functions in melanoma remain unknown. OBJECTIVE: This study aims to confirm the expression of Dock180 and Elmo1, their underlying mechanisms, and roles in melanoma. METHODS: Both immunohistochemical staining and Western blotting were used to confirm expression of Dock180 and Elmo1 in human melanoma. To identify roles of Dock180 and Elmo1 in cell survival, apoptosis and migration, downregulation of Dock180 or Elmo1 in melanoma cells with small interfering RNA (siRNA) was performed. RESULTS: We identified overexpression of Dock180 and Elmo1 in human melanoma compared to normal skin ex vivo. Inhibition of Dock180 or Elmo1 following siRNA in melanoma cells reduced cell viability and increased apoptosis as supported by increased proportion of cells with Annexin V-PE (+) staining and sub-G0/G1 peak in cell cycle analysis. Moreover, inhibition of Dock180 or Elmo1 regulated apoptosis-related proteins, showing downregulation of Bcl-2, caspase-3, and PARP and upregulation of Bax, PUMA, cleaved caspase-3, and cleaved PARP. Furthermore, knockdown of Dock180 and Elmo1 in melanoma cells reduced cell migration and changed cellular signaling pathways including ERK and AKT. Vemurafenib decreased cell viability in concentration-dependent manner, while transfection with Dock180- or Elmo1-specific siRNA in melanoma cells significantly reduced cell viability. CONCLUSION: Our results suggest that both Dock180 and Elmo1 may be associated with cancer progression, and can be potential targets for treatment of melanoma.
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BACKGROUND: Doxycycline is one of the most prescribed antibiotics by dermatologists. However, the concern regarding adverse events of doxycyline has been rising. OBJECTIVE: To detect the adverse events of doxycycline using the Korea Adverse Events Reporting System (KAERS) database from January 2014 to December 2018 through a data mining method. METHODS: A signal was defined as one satisfying all three indices; a proportional reporting ratio, a reporting odds ratio, and an information component. We further checked whether the detected signals exist in drug labels in Korea and five developed countries, the United States, the United Kingdom, Germany, Canada, and Japan. RESULTS: A total of 3,365,186 adverse event-drug pairs were reported and of which 3,075 were associated with doxycycline. Among the thirty-seven signals, nineteen (malaise, ileus, confusion, malignant neoplasm, ectopic pregnancy, ovarian hyperstimulation, vaginal hemorrhage, bone necrosis, acne, rosacea, seborrheic dermatitis, folliculitis, skin ulceration, crusting, dry skin, paronychia, mottled skin, application site reaction, and application site edema) were not included on any of the drug labels of the six countries. CONCLUSION: We identified nineteen new doxycycline signals that did not appear on drug labels in six countries. Further studies are warranted to evaluate the causality of the adverse events with doxycycline.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Mineração de Dados , Bases de Dados Factuais , Doxiciclina/efeitos adversos , Feminino , Humanos , Estados UnidosRESUMO
We investigated the effects of mesenchymal stem cells (MSCs) on wound healing using a three-dimensional (3D) collagen gel scaffold. Three circular full-thickness skin defects were created on the back of Sprague-Dawley rats. One site was covered with a 3D collagen gel containing 2 × 10(6) MSCs (MSCs+/3D collagen+). Another site was replaced with a 3D collagen gel without MSCs and the third site was left empty. The wound size was significantly reduced in the MSCs+/3D collagen+ sites. MSCs+/3D collagen+ sites exhibited the most neovascularization. FISH showed that Y-chromosome possessing cells were found within the dermis of MSCs+/3D collagen+ sites. Gelatin zymography revealed that the most intense expression of MMP-9 was detected early in the MSCs+/3D collagen+ sites. Our results indicate that MSCs upregulate the early expression of MMP-9 which induces the early mobilization of VEGF. Thus, MSCs appear to accelerate significantly wound healing via early activation of MMP-9 and VEGF.
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Metaloproteinase 9 da Matriz/metabolismo , Células-Tronco Mesenquimais/citologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização , Animais , Colágeno/farmacologia , Feminino , Imuno-Histoquímica , Transplante de Células-Tronco Mesenquimais , Neovascularização Fisiológica , Ratos , Ratos Sprague-Dawley , Pele/patologiaRESUMO
Atopic dermatitis (AD) has been increasing worldwide over the past few decades. AD has been reported to be associated with an increased risk of osteoporosis and fractures in adult AD patients. The aim of this study was to investigate the bone mineral density (BMD) to evaluate osteoporosis risk in young adults with AD by sex. This was a case-control cohort study using a national dataset from the Korea National Health and Nutrition Examination Survey 2007-2009. We included young adult AD patients (men aged 19 ≤ and < 50 years, premenopausal women aged 19 ≤ and < 50 years) and 1:5 propensity score weighting controls by age, sex, body mass index (BMI), vitamin D level, and alcohol/smoking status. BMD was measured by double energy X-ray absorptiometry at the lumbar spine, femur neck, and total femur. The prevalence of low BMD, defined by a Z-score ≤ - 2.0, was compared between AD and without AD. We analyzed 311 (weighted n = 817,014) AD patients and 8,972 (weighted n = 20,880,643) controls. BMD at the lumbar spine was significantly lower in the male AD group than in the male control group (mean ± SE, 0.954 ± 0.016 vs. 0.989 ± 0.002, P = 0.03). The prevalence of low BMD (Z-score) did not significantly differ between AD and non-AD subjects in both men (3.8% vs. 2.7%, P = 0.56) and women (6.4% vs. 3.3%, P = 0.40). Among AD patients, early age at diagnosis of AD, longer duration of AD, lower BMI, rural residence (for men), less education, low vitamin D level, late menarche, and more pregnancies (for women) were associated with low BMD. In conclusion, low BMD did not occur more frequently in young adults with AD than in non-AD controls. However, early-onset/longer AD duration and lower BMI were associated with low BMD among young adult patients with AD.
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Densidade Óssea , Dermatite Atópica/complicações , Dermatite Atópica/diagnóstico , Osteoporose/complicações , Osteoporose/diagnóstico , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Estudos Transversais , Bases de Dados Factuais , Densitometria , Feminino , Fêmur/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Humanos , Incidência , Vértebras Lombares/diagnóstico por imagem , Masculino , Inquéritos Nutricionais , Prevalência , República da Coreia , População Rural , Fatores Sexuais , Inquéritos e Questionários , Adulto JovemRESUMO
Cutaneous melanoma is known to be one of the most dangerous skin cancers because of its metastatic functions. Today, it is essential to investigate specific biomarkers for the target treatment in many diseases including cancers. DJ-1 protein, also known as Parkinson disease 7, has various functions associated with cancer progression including cell survival and migration. Phosphatase and tensin homolog (PTEN) is a tumor suppressor that regulates the PI3K/AKT signaling pathway and its mutations have been reported to frequently occur in many cancers such as thyroid, breast and skin. Recently, DJ-1 has been identified as a negative regulator of PTEN in many human cancer cells. However, the impacts and relationship of DJ-1 and PTEN have not been studied yet in melanoma. To confirm the expression of DJ-1 and PTEN in melanoma compared to normal skin tissues and find out functions of DJ-1 in melanoma cells, Western blot analysis and immunohistochemical staining were used. Transfection of G361 cells with DJ-1-specific small interfering RNA was performed to figure out the roles of DJ-1 and the relationship between DJ-1 and PTEN in melanoma cells. In our study, the DJ-1 protein was significantly increased with loss of PTEN protein in melanoma compared to that in normal skin. Inhibition of DJ-1 in G361 cells induced apoptosis, and suppressed cell survival and migration. Furthermore, suppression of DJ-1 in G361 cells increased the expression of cleaved caspase-3, cleaved PARP, Bax, p53, and Daxx as well as PTEN, while it decreased expression of survivin, caspase-3, and PARP. Also, downregulated DJ-1 inhibited phosphorylation of AKT in G361 cells. Collectively, DJ-1 overexpression could affect the proliferative and invasive capabilities of melanoma cells via regulating the PTEN/AKT pathway and apoptosis-related proteins. This study suggests that DJ-1 may be a potential target for the treatment of melanoma.
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Melanoma/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteína Desglicase DJ-1/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Cutâneas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Melanoma/patologia , Melanoma/cirurgia , Fosforilação/genética , Proteína Desglicase DJ-1/metabolismo , Transdução de Sinais/genética , Pele/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Regulação para CimaRESUMO
Aged human skin is fragile because of fragmentation and loss of type I collagen fibrils, which confer strength and resiliency. We report here that dermal fibroblasts express increased levels of collagen-degrading matrix metalloproteinases-1 (MMP-1) in aged (>80 years old) compared with young (21 to 30 years old) human skin in vivo. Transcription factor AP-1 and alpha2beta1 integrin, which are key regulators of MMP-1 expression, are also elevated in fibroblasts in aged human skin in vivo. MMP-1 treatment of young skin in organ culture causes fragmentation of collagen fibrils and reduces fibroblast stretch, consistent with reduced mechanical tension, as observed in aged human skin. Limited fragmentation of three-dimensional collagen lattices with exogenous MMP-1 also reduces fibroblast stretch and mechanical tension. Furthermore, fibroblasts cultured in fragmented collagen lattices express elevated levels of MMP-1, AP-1, and alpha2beta1 integrin. Importantly, culture in fragmented collagen raises intracellular oxidant levels and treatment with antioxidant MitoQ(10) significantly reduces MMP-1 expression. These data identify positive feedback regulation that couples age-dependent MMP-1-catalyzed collagen fragmentation and oxidative stress. We propose that this self perpetuating cycle promotes human skin aging. These data extend the current understanding of the oxidative theory of aging beyond a cellular-centric view to include extracellular matrix and the critical role that connective tissue microenvironment plays in the biology of aging.
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Colágeno Tipo I/metabolismo , Fibroblastos/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Estresse Oxidativo/fisiologia , Envelhecimento da Pele/fisiologia , Adulto , Fatores Etários , Idoso de 80 Anos ou mais , Antioxidantes/farmacologia , Western Blotting , Fibroblastos/patologia , Imunofluorescência , Humanos , Integrina alfa2beta1/metabolismo , Microdissecção , Técnicas de Cultura de Órgãos , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/análise , Espécies Reativas de Oxigênio , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Envelhecimento da Pele/patologia , Fator de Transcrição AP-1/metabolismoRESUMO
BACKGROUND: Pathologic scars can lead to itching, erythema, and psychological stress due to cosmetic problems. Bleomycin, one of anticancer agents, has been used for treating keloid or hypertrophic scar. Some studies have shown that bleomycin can induce markedly scar improvement. AIMS: To evaluate the efficacy of bleomycin compared to corticosteroid as well as other treatments for keloid or hypertrophic scar using meta-analysis methods. METHODS: A computerized search was performed in different databases including Cochrane, Embase, and PubMed. Three randomized controlled trials (RCTs) and two controlled clinical trials (CCTs) were included. Then, statistical analyses of extracted outcome data from the studies were calculated using Rex (version 3.0.1; RexSoft Inc). RESULTS: Scar improvement was significantly increased in the bleomycin group compared to the triamcinolone acetonide (TAC) group (SMD: 0.59, 95% CI: 0.30-0.88, P < .0001). In addition, there was also statistically significant difference between the bleomycin group and the 5-FU group (SMD: 1.37, 95% CI: 0.88-1.85, P < .0001). Bleomycin increased relatively scar improvement compared to TAC combined with 5-FU, although there was no statistical difference (SMD: 0.63, 95% CI: -0.59-1.84, P = .3108). Furthermore, bleomycin demonstrated significantly increased improvement of scar compared to TAC combined with cryotherapy (SMD: 1.11, 95% CI: 0.48-1.74, P = .0006). CONCLUSIONS: This meta-analysis found that bleomycin was more effective for treating keloid or hypertrophic scar than other treatments including TAC, 5-FU, TAC combined with 5-FU, and TAC combined with cryotherapy. However, further comprehensive studies, including randomized controlled trials, are needed to perform objective analysis.
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Cicatriz Hipertrófica , Queloide , Bleomicina/efeitos adversos , Cicatriz Hipertrófica/tratamento farmacológico , Cicatriz Hipertrófica/etiologia , Cicatriz Hipertrófica/patologia , Humanos , Injeções Intralesionais , Queloide/tratamento farmacológico , Queloide/patologia , Resultado do TratamentoRESUMO
PURPOSE: We investigated the expression of Nrf2 in colorectal cancer and its correlation with clinicopathological characteristics as well as mechanisms and roles of Nrf2 expression including cell signaling pathway, survival, proliferation, and migration. METHODS: Nrf2 expression was measured in 12 and 30 different colorectal cancer (CRC) tissues by western blot (WB) and immunohistochemistry (IHC), respectively. SW480 cells were used for cell proliferation and cell migration tests. The correlation between the expression of Nrf2 and clinicopathologic parameters were evaluated using the chi-square or Fisher exact test. Data are expressed as the mean ± standard deviation for 3 independent experiments. P < 0.05 was considered statistically significant. RESULTS: Analysis of WB demonstrated that Nrf2 proteins were increased in CRC tissues, and decreased in normal tissues. IHC staining showed that the Nrf2 expression was elevated in CRC tissues, compared to matched normal tissues. When SW480 cells were suppressed with small interfering RNA of Nrf2, cell viability was inhibited, and cell apoptosis was increased. These results were found along with suppression of the phosphorylated form of extracellular signal-regulated kinase 1/2 and AKT. CONCLUSION: This study suggests that overexpression of Nrf2 may be related to carcinogenesis and progression of CRC.
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BACKGROUND: Oral isotretinoin (Iso) is one of the most commonly used drugs for patients with moderate-to-severe acne; however, its use has been associated with several adverse effects. Some studies have suggested an association between Iso therapy and homocysteine (Hcy), folic acid, and vitamin B12 plasma levels. OBJECTIVE: To evaluate the changes in plasma Hcy, folic acid, and vitamin B12 levels during Iso therapy for acne using meta-analytic methods. METHODS: Five scientific databases (MEDLINE, EMBASE, Cochrane Library, SCOPUS, and Web of Science) were searched according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines up to December 2018. A review of 734 publications identified 10 studies that assessed plasma levels of Hcy, folic acid, and vitamin B12 during Iso therapy in acne patients. RESULTS: A total of 10 studies consisting of 592 patients were included in the meta-analysis. Plasma Hcy levels were significantly increased after Iso therapy (weighted mean difference [WMD]: 2.99, 95% confidence interval [CI]: 1.78-4.20, I2 = 86%), whereas folic acid levels were significantly decreased after Iso therapy (WMD: -1.03, 95% CI: -1.90 to -0.17, I2 = 89%). CONCLUSIONS: This meta-analysis found that Iso therapy was associated with changes in plasma levels of Hcy and folic acid in acne patients. However, further evaluation in controlled studies is needed to verify these results.
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Acne Vulgar/tratamento farmacológico , Ácido Fólico/sangue , Homocisteína/sangue , Isotretinoína/administração & dosagem , Vitamina B 12/sangue , Acne Vulgar/sangue , Administração Oral , Humanos , Isotretinoína/efeitos adversosRESUMO
Heat shock protein 70 (HSP70), a chaperone protein associated with tumorigenesis and chemoresistance, has attracted significant attention as a potential therapeutic target for the development of anticancer drugs. Here, the effects of pifithrin-µ, an effective dual inhibitor of HSP70 and p53, on anticancer activities and epithelial-mesenchymal transition (EMT) were investigated in malignant mesothelioma (MM) cells. MSTO-211HAcT cells, pre-incubated in a medium containing lactic acid, showed more potent resistance to cisplatin and gemcitabine, compared with their acid-sensitive parental MSTO-211H cells. Pifithrin-µ treatment induced both apoptosis and necroptosis, which were accompanied by an EMT-like phenomenon, as evidenced by an elongated cell morphology, decreased levels of epithelial cell markers including E-cadherin, claudin-1, and ß-catenin, increased levels of mesenchymal markers including Snail, Slug, and vimentin, and increased cell migratory property. Moreover, pifithrin-µ increased intracellular ROS levels, which is associated with mitochondrial dysfunction and decreased cellular ATP content. A series of changes caused by pifithrin-µ treatment were effectively restored by lowering the ROS level through pretreatment with N-acetylcysteine. Collectively, our results suggest that pifithrin-µ may promote the metastatic behavior of surviving cells by triggering the EMT, despite its effective cell-killing action against MM cells, possibly linked to oxidative mitochondrial dysfunction and ATP depletion.