Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 83
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biomolecules ; 10(4)2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32231102

RESUMO

Exposure to particulate matter (PM) has been linked to pulmonary and cardiovascular dysfunctions, as well as skin diseases, etc. PM impairs the skin barrier functions and is also involved in the initiation or exacerbation of skin inflammation, which is linked to the activation of reactive oxygen species (ROS) pathways. Fullerene is a single C60 molecule which has been reported to act as a good radical scavenger. However, its poor water solubility limits its biological applications. The glyco-modification of fullerenes increases their water solubility and anti-bacterial and anti-virus functions. However, it is still unclear whether it affects their anti-inflammatory function against PM-induced skin diseases. Hence, glycofullerenes were synthesized to investigate their effects on PM-exposed HaCaT human keratinocytes. Our results showed that glycofullerenes could reduce the rate of PM-induced apoptosis and ROS production, as well as decrease the expression of downstream mitogen-activated protein kinase and Akt pathways. Moreover, PM-induced increases in inflammatory-related signals, such as cyclooxygenase-2, heme oxygenase-1, and prostaglandin E2, were also suppressed by glycofullerenes. Notably, our results suggested that PM-induced impairment of skin barrier proteins, such as filaggrin, involucrin, repetin, and loricrin, could be reduced by pre-treatment with glycofullerenes. The results of this study indicate that glycofullerenes could be potential candidates for treatments against PM-induced skin diseases and that they exert their protective effects via ROS scavenging, anti-inflammation, and maintenance of the expression of barrier proteins.

2.
J Cell Physiol ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31990056

RESUMO

Apoptosis and fibrosis play a vital role in myocardial infarction (MI) induced tissue injury. Although microRNAs have been the focus of many studies on cardiac apoptosis and fibrosis in MI, the detailed effects of miR-26a is needed to further understood. The present study demonstrated that miR-26a was downregulated in ST-elevation MI (STEMI) patients and oxygen-glucose deprivation (OGD)-treated H9c2 cells. Downregulation of miR-26a was closely correlated with the increased expression of creatine kinase, creatine kinase-MB and troponin I in STEMI patients. Further analysis identified that ataxia-telangiectasia mutated (ATM) was a target gene for miR-26a based on a bioinformatics analysis. miR-26a overexpression effectively reduced ATM expression, apoptosis, and apoptosis-related proteins in OGD-treated H9c2 cells. In a mouse model of MI, the expression of miR-26a was significantly decreased in the infarct zone of the heart, whereas apoptosis and ATM expression were increased. miR-26a overexpression effectively reduced ATM expression and cardiac apoptosis at Day 1 after MI. Furthermore, we demonstrated that overexpression of miR-26a improved cardiac function and reduced cardiac fibrosis by the reduced expression of collagen type I and connective tissue growth factor (CTGF) in mice at Day 14 after MI. Overexpression of miR-26a or ATM knockdown decreased collagen I and CTGF expression in cultured OGD-treated cardiomyocytes. Taken together, these data demonstrate a prominent role for miR-26a in linking ATM expression to ischemia-induced apoptosis and fibrosis, key features of MI progression. miR-26a reduced MI development by affecting ATM expression and could be targeted in the treatment of MI.

3.
Clin Sci (Lond) ; 133(21): 2171-2187, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31696218

RESUMO

Several diseases have been linked to particulate matter (PM) exposure. Outdoor activities, such as road running or jogging, are popular aerobic exercises due to few participatory limitations. Osteoarthritis (OA) is a progressive degenerative joint disease, usually observed at age 40, and not noticed before pain or diagnosis. Although exercise has health benefits, it is unclear whether outdoor jogging in higher PM (standard reference material 1649b, SRM 1649b) concentration environments could affect OA development or severity. Hence, a PM exposure monosodium iodoacetate (MIA)-induced OA animal jogged model was established for investigation. Results showed that high doses of PM (5 mg) significantly increased pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, and IL-6, and M1 macrophages in the lung region, also obtained in systemic IL-6 and TNF-α expressions in this MIA-OA rat model. Moreover, levels of osteocalcin, cartilage oligomeric matrix protein (COMP), and N-telopeptides of type I collagen were especially influenced in MIA+PM groups. Morphological and structural changes of the knee joint were detected by micro-computed tomography images (micro-CT) and immunohistochemistry. MIA + PM rats exhibited severe bone density decrease, cartilage wear, and structure damages, accompanied by lower levels of physical activity, than the sham group and groups receiving MIA or PM alone. The findings suggest that the severity of OA could be promoted by PM exposure with a PM concentration effect via systemic inflammatory mechanisms. To the best of our knowledge, this is the first study to provide direct effects of PM exposure on OA severity.

4.
Int J Mol Sci ; 20(17)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480310

RESUMO

Particulate matter (PM), a widespread air pollutant, consists of a complex mixture of solid and liquid particles suspended in air. Many diseases have been linked to PM exposure, which induces an imbalance in reactive oxygen species (ROS) generated in cells, and might result in skin diseases (such as aging and atopic dermatitis). New techniques involving nanomedicine and nano-delivery systems are being rapidly developed in the medicinal field. Fullerene, a kind of nanomaterial, acts as a super radical scavenger. Lower water solubility levels limit the bio-applications of fullerene. Hence, to improve the water solubility of fullerene, while retaining its radical scavenger functions, a fullerene derivative, fullerenol C60(OH)36, was synthesized, to examine its biofunctions in PM-exposed human keratinocyte (HaCaT) cells. The PM-induced increase in ROS levels and expression of phosphorylated mitogen-activated protein kinase and Akt could be inhibited via fullerenol pre-treatment. Furthermore, the expression of inflammation-related proteins, cyclooxygenase-2, heme oxygenase-1, and prostaglandin E2 was also suppressed. Fullerenol could preserve the impaired state of skin barrier proteins (filaggrin, involucrin, repetin, and loricrin), which was attributable to PM exposure. These results suggest that fullerenol could act against PM-induced cytotoxicity via ROS scavenging and anti-inflammatory mechanisms, and the maintenance of expression of barrier proteins, and is a potential candidate compound for the treatment of skin diseases.


Assuntos
Poluição do Ar/prevenção & controle , Fulerenos/análise , Material Particulado/toxicidade , Água/química , Apoptose/efeitos dos fármacos , Linhagem Celular , Cidades , Fulerenos/química , Humanos , Inflamação/patologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/ultraestrutura , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Modelos Biológicos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Solubilidade
6.
J Clin Med ; 8(6)2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31181643

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) causes superficial infections such as cellulitis or invasive infections such as osteomyelitis; however, differences in MRSA isolates from cellulitis (CL-MRSA) and from osteomyelitis (OM-MRSA) at the same local area remain largely unknown. A total of 221 MRSA isolates including 106 CL-MRSA strains and 115 OM-MRSA strains were collected at Chang-Gung Memorial Hospital in Taiwan between 2016 and 2018, and their genotypic and phenotypic characteristics were compared. We found that OM-MRSA isolates significantly exhibited higher rates of resistance to multiple antibiotics than CL-MRSA isolates. Genotypically, OM-MRSA isolates had higher proportions of the SCCmec type III, the sequence type ST239, and the spa type t037 than CL-MRSA isolates. Besides the multidrug-resistant lineage ST239-t037-SCCmecIII more prevalent in OM-MRSA, higher antibiotic resistance rates were also observed in several other prevalent lineages in OM-MRSA as compared to the same lineages in CL-MRSA. Furthermore, when prosthetic joint infection (PJI) associated and non-PJI-associated MRSA strains in osteomyelitis were compared, no significant differences were observed in antibiotic resistance rates between the two groups, albeit more diverse genotypes were found in non-PJI-associated MRSA. Our findings therefore suggest that deep infections may allow MRSA to evade antibiotic attack and facilitate the convergent evolution and selection of multidrug-resistant lineages.

7.
Mol Immunol ; 112: 163-174, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31153046

RESUMO

Exposure to airborne particulate matter (PM) not only causes lung inflammation and chronic respiratory diseases, but also increases the incidence and mortality of cardiopulmonary diseases. The nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome activation has been shown to play a critical role in the formation of many chronic disorders. On the other hand, carbon monoxide (CO) has been shown to possess anti-inflammatory and antioxidant effects in many tissues and organs. Here, we investigated the effects and mechanisms of carbon monoxide releasing molecule-2 (CORM-2) on PM-induced inflammatory responses in human pulmonary alveolar epithelial cells (HPAEpiCs). We found that PM induced C-reactive protein (CRP) expression, NLRP3 inflammasome activation, IL-1ß secretion, and caspase-1 activation, which were inhibited by pretreatment with CORM-2. In addition, transfection with siRNA of Toll-like receptor 2 (TLR2) or TLR4 and pretreatment with an antioxidant (N-acetyl-cysteine, NAC), the inhibitor of NADPH oxidase (diphenyleneiodonium, DPI), or a mitochondria-specific superoxide scavenger (MitoTEMPO) reduced PM-induced inflammatory responses. CORM-2 also inhibited PM-induced NADPH oxidase activity and NADPH oxidase- and mitochondria-derived ROS generation. However, pretreatment with inactivate CORM-2 (iCORM-2) had no effects on PM-induced inflammatory responses. Finally, we showed that CORM-2 inhibited PM-induced CRP, NLRP3 inflammasome, and ASC protein expression in the lung tissues of mice and IL-1ß levels in the serum of mice. PM-enhanced leukocyte count in bronchoalveolar lavage fluid in mice was reduced by CORM-2. The results of this study suggested a protective role of CORM-2 in PM-induced lung inflammation by inhibiting the TLR2 and TLR4/ROS-NLRP3 inflammasome-CRP axial.


Assuntos
Inflamassomos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Compostos Organometálicos/farmacologia , Pneumonia/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/imunologia , Animais , Líquido da Lavagem Broncoalveolar , Monóxido de Carbono/efeitos adversos , Caspase 1/metabolismo , Humanos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Material Particulado/efeitos adversos , Pneumonia/induzido quimicamente , Pneumonia/metabolismo , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos
8.
Int J Nanomedicine ; 14: 469-481, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30666108

RESUMO

Background: Periprosthetic joint infections (PJIs) have a high incidence of recurrence after total joint replacement and are difficult to treat by debridement or antibiotic treatment. Curcumin is a natural product with anti-inflammatory and anti-bacterial properties. The low bioactivity of curcumin in water restricts its clinical application. Curcumin nanoparticles (CURN) were developed to overcome this limitation. Methods: In this study, the therapeutic effects of CURN and their anti-inflammatory functions were investigated in a Staphylococcus aureus biofilm-induced PJIs model. Results: CURN first attenuated the biofilm-induced expansion of myeloid-derived suppressor cells (MDSCs) and then regulated M1- and M2-phenotypic MDSC expression. Down-regulation of cytokines and reactive oxygen species was considered as the mechanism of CURN in reversing the suppression of T cell proliferation. The recovery of bone permeative destruction demonstrated that CURN enhanced therapeutic potency of vancomycin in vivo. Conclusion: This is the first study to demonstrate that CURN may be useful for treating PJIs.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Curcumina/farmacologia , Nanopartículas/administração & dosagem , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Células Cultivadas , Curcumina/administração & dosagem , Citocinas/metabolismo , Articulação do Quadril/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infecções Relacionadas à Prótese/complicações , Infecções Relacionadas à Prótese/microbiologia , Espécies Reativas de Oxigênio/metabolismo , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/microbiologia
9.
J Cell Physiol ; 234(8): 13157-13168, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30549031

RESUMO

Osteosarcoma is a malignant primary bone tumor that responds poorly to both chemotherapy and radiation therapy. However, because of side effects and drug resistance in chemotherapy and the insufficiency of an effective adjuvant therapy for osteosarcoma, it is necessary to research novel treatments. This study was the first to investigate the anticancer effects of the flavonoid derivative artocarpin in osteosarcoma. Artocarpin induced cell apoptosis in three human osteosarcoma cell lines-U2OS, MG63, and HOS. Artocarpin was also associated with increased intracellular reactive oxygen species (ROS). Mitochondrial dysfunction was followed by the release of cytochrome c from mitochondria and accompanied by decreased antiapoptotic Bcl-2 and Bcl-xL and increased proapoptotic protein Bak and Bax. Artocarpin triggered endoplasmic reticulum (ER) stress, as indicated by changes in cytosol calcium levels and increased glucose-regulated protein 78 and 94 expressions, and also increased calpains expression and activity. Animal studies revealed a dramatic 40% reduction in tumor volume after 18 days of treatment. This study demonstrated a novel anticancer activity of artocarpin against human osteosarcoma cells and in murine tumor models. In summary, artocarpin significantly induced cell apoptosis through ROS, ER stress, mitochondria, and the caspase pathway, and may thus be a novel anticancer treatment for osteosarcoma.

11.
Int J Mol Sci ; 19(9)2018 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-30200660

RESUMO

Malignant melanoma is developed from pigment-containing cells, melanocytes, and primarily found on the skin. Malignant melanoma still has a high mortality rate, which may imply a lack of therapeutic agents. Lakoochin A, a compound isolated from Artocarpus lakoocha and Artocarpus xanthocarpus, has an inhibitory function of tyrosinase activity and melanin production, but the anti-cancer effects are still unclear. In the current study, the therapeutic effects of lakoochin A with their apoptosis functions and possible mechanisms were investigated on A375.S2 melanoma cells. Several methods were applied, including 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT), flow cytometry, and immunoblotting. Results suggest that lakoochin A attenuated the growth of A375.S2 melanoma cells through an apoptosis mechanism. Lakoochin A first increase the production of cellular and mitochondrial reactive oxygen species (ROSs); mitochondrial ROSs then promote mitogen-activated protein kinases (MAPKs) pathway activation and raise downstream apoptosis-related protein and caspase expression. This is the first study to demonstrate that lakoochin A, through ROS-MAPK, apoptosis-related proteins, caspases cascades, can induce melanoma cell apoptosis and may be a potential candidate compound for treating malignant melanoma.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Melanoma/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estilbenos/farmacologia , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melanoma/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo
12.
PLoS One ; 13(8): e0202501, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30125327

RESUMO

Small wear particles (0.1-10 µm) in total joint replacement are generally considered as the major causative agent leading to periprosthetic inflammation and osteolysis. However, little is known about the roles of larger wear particles (10-100 µm) in periprosthetic inflammation and osteolysis. Additionally, although ample studies demonstrated that increased oxidative stress is critically involved in particle-induced inflammation and osteolysis, detailed changes in antioxidant enzymes expression in the disease development remain largely unclear. Herein, we used a rat knee prosthesis model to assess effects of polyethylene (PE) particles (20-60 µm) on the levels of oxidative stress markers such as malondialdehyde (MDA) and total antioxidant capacity (TAC) in blood plasma, and on the expression profiles of antioxidant enzymes in knee joint tissues. In combination with a forced-exercise intervention for all surgical rats, we found that the rat groups treated with both artificial joint and PE particles exhibited higher MDA levels and lower TAC levels, together with lower levels of physical activity and higher levels of inflammatory markers, than the sham group and the groups receiving artificial joint or PE particles alone at weeks 20-24 post-operatively. Dose-response relationships between the exposure to PE particles and the induction of oxidative stress and inflammation were also observed in the artificial joint/PE groups. Under such conditions, we unexpectedly found that most of antioxidant enzymes displayed pronounced up-regulation, with concomitant induction of inflammatory and osteoclast-inducing factors (including IL-1ß, NF-κB and RANKL), in the artificial joint/PE groups as compared to the sham, artificial joint only, or PE only group. Only a few antioxidant enzymes including SOD2 and GPx2 showed down-regulation. Collectively, our findings demonstrate that implantation of artificial joint along with large PE particles synergistically trigger the induction of oxidative stress; however, down-regulation of many antioxidant enzymes may not necessarily occur during the disease development.


Assuntos
Interface Osso-Implante , Implantes Experimentais/efeitos adversos , Osteoclastos/metabolismo , Osteólise/metabolismo , Estresse Oxidativo , Polietileno/efeitos adversos , Animais , Glutationa Peroxidase/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/metabolismo , Masculino , Malondialdeído/metabolismo , NF-kappa B/metabolismo , Osteoclastos/patologia , Osteólise/induzido quimicamente , Osteólise/patologia , Tamanho da Partícula , Ligante RANK/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
13.
Biochem Pharmacol ; 155: 537-546, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30031810

RESUMO

Thrombospondin (TSP)-2, a matricellular glycoprotein of the TSP family, regulates multiple biological functions, including proliferation, angiogenesis, cell adhesion, and extracellular matrix (ECM) modeling. The clinical relevance of TSP-2 has been explored in many different cancers. TSP-2 expression levels vary between different cancer types, and their role in tumor progression remains controversial. Although previous studies have reported higher serum TSP-2 levels in patients with non-small cell lung cancer, the role of TSP-2 in lung cancer progression remains to be addressed. A total of 585 lung adenocarcinoma datasets, including mRNA sequencing and clinical data, were retrieved from The Cancer Genome Atlas (TCGA). Forty paired adjacent normal tissues and lung tumor tissue datasets were used to examine TSP-2 expression levels. Tumor microarray were performed with immunohistochemical staining to examine TSP-2 expression in lung cancer patients. Transwell migration assay, quantitative real-time PCR and Western blot were used to investigate molecular mechanism of TSP-2 in lung cancer cell. TSP-2 promotes matrix metalloproteinase-13 (MMP-13) expression, cell migration, and cell invasion by mediating integrin αvß3/FAK/Akt/NF-κB signal transduction. Using TSP-2 knockdown stable cell lines, we found that TSP-2 knockdown reduces MMP-13 expression and cell mobility. When we manipulated the tumor tissue microarray and TCGA datasets to investigate the clinical relevance of TSP-2, we found high TSP-2 expression levels in lung cancer specimens. The present study demonstrates that TSP-2 regulates cell mobility through MMP-13 expression in lung cancer cells. In addition, TSP-2 expression was associated with MMP-13 expression and poor prognosis in lung cancer. TSP-2 may therefore be a promising novel target for lung cancer treatment.


Assuntos
Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/enzimologia , Metaloproteinase 13 da Matriz/biossíntese , Trombospondinas/biossíntese , Células A549 , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Indução Enzimática/efeitos dos fármacos , Indução Enzimática/fisiologia , Humanos , Neoplasias Pulmonares/patologia , Invasividade Neoplásica/patologia , Trombospondinas/toxicidade
14.
Redox Biol ; 18: 93-103, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30007888

RESUMO

Pseudomonas aeruginosa (P. aeruginosa) infection in the lung is common in patients with cystic fibrosis (CF). Intercellular adhesion molecule-1 (ICAM-1) is known to play a key role in lung inflammation. Acute inflammation and its timely resolution are important to ensure bacterial clearance and limit tissue damage. Carbon monoxide (CO) has been shown to exert anti-inflammatory effects in various tissues and organ systems. Here, we explored the protective effects and mechanisms of carbon monoxide releasing molecule-2 (CORM-2) on P. aeruginosa-induced inflammatory responses in human pulmonary alveolar epithelial cells (HPAEpiCs). We showed that P. aeruginosa induced prostaglandin E2 (PGE2)/interleukin-6 (IL-6)/ICAM-1 expression and monocyte adherence to HPAEpiCs. Moreover, P. aeruginosa-induced inflammatory responses were inhibited by transfection with siRNA of Toll-like receptor 4 (TLR4), PKCα, p47phox, JNK2, p42, p50, or p65. P. aeruginosa also induced PKCα, JNK, ERK1/2, and NF-κB activation. We further demonstrated that P. aeruginosa increased intracellular ROS generation via NADPH oxidase activation. On the other hand, P. aeruginosa-induced inflammation was inhibited by pretreatment with CORM-2. Preincubation with CORM-2 had no effects on TLR4 mRNA levels in response to P. aeruginosa. However, CORM-2 inhibits P. aeruginosa-induced inflammation by decreasing intracellular ROS generation. P. aeruginosa-induced PKCα, JNK, ERK1/2, and NF-κB activation was inhibited by CORM-2. Finally, we showed that P. aeruginosa induced levels of the biomarkers of inflammation in respiratory diseases, which were inhibited by pretreatment with CORM-2. Taken together, these data suggest that CORM-2 inhibits P. aeruginosa-induced PGE2/IL-6/ICAM-1 expression and lung inflammatory responses by reducing the ROS generation and the inflammatory pathways.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Molécula 1 de Adesão Intercelular/imunologia , Compostos Organometálicos/farmacologia , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/imunologia , Espécies Reativas de Oxigênio/imunologia , Células Epiteliais Alveolares/imunologia , Células Epiteliais Alveolares/microbiologia , Animais , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Humanos , Inflamação/complicações , Inflamação/tratamento farmacológico , Inflamação/imunologia , Interleucina-6/imunologia , Masculino , Camundongos Endogâmicos ICR , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos
15.
Int J Nanomedicine ; 13: 3279-3293, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29910615

RESUMO

Background: 7,3',4'-Trihydroxyisoflavone (734THI), a secondary metabolite derived from daidzein in soybean, possesses several biological activities, including antioxidant, skin whitening and anti-atopic dermatitis properties, but the poor aqueous solubility of 734THI has limited its application in medicine and cosmetic industry. Methods: The aim of the present study was to improve the physicochemical properties of 734THI using planetary ball mill preparation under a solvent-free process to improve its solubility and anti-pollutant activity. Results: 734THI nanoparticle powder (734THIN) was successfully prepared by the planetary ball mill technique using polyvinylpyrrolidone K30 as the excipient. 734THIN effectively increased the aqueous solubility and cellular uptake of 734THI by improving its physicochemical properties, including particle size reduction, crystalline-amorphous transformation and intermolecular hydrogen bonding with polyvinylpyrrolidone K30. In addition, 734THIN inhibited the overexpression of COX-2 and MMP-9 by downregulating MAPK pathway signaling in particulate matter-exposed HaCaT keratinocytes, while raw 734THI in PBS with low aqueous solubility did not show any anti-inflammatory or antiaging activity. Conclusion: 734THIN may be used as an additive in anti-pollutant skin care products for preventing particulate matter-induced inflammation and aging in skin.


Assuntos
Isoflavonas/química , Isoflavonas/farmacologia , Queratinócitos/efeitos dos fármacos , Nanopartículas/química , Material Particulado/efeitos adversos , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo/efeitos dos fármacos , Excipientes/química , Humanos , Ligação de Hidrogênio , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Povidona/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
16.
Front Pharmacol ; 9: 411, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29770114

RESUMO

Glioblastoma multiforme (GBM) is an extremely aggressive and devastating malignant tumor in the central nervous system. Its incidence is increasing and the prognosis is poor. Artocarpin is a natural prenylated flavonoid with various anti-inflammatory and anti-tumor properties. Studies have shown that artocarpin is associated with cell death of primary glioblastoma cells. However, the in vivo effects and the cellular and molecular mechanisms modulating the anticancer activities of artocarpin remain unknown. In this study, we demonstrated that treating the glioblastoma cell lines U87 and U118 cells with artocarpin induced apoptosis. Artocarpin-induced apoptosis is associated with caspase activation and poly (ADP-ribose) polymerase (PARP) cleavage and is mediated by the mitochondrial pathway. This is associated with mitochondrial depolarization, mitochondrial-derived reactive oxidative species (ROS) production, cytochrome c release, Bad and Bax upregulations, and Bcl-2 downregulation. Artocarpin induced NADPH oxidase/ROS generation plays an important role in the mitochondrial pathway activation. Furthermore, we found artocarpin-induced ROS production in mitochondria is associated with Akt- and ERK1/2 activation. After treatment with artocarpin, ROS causes PI3K/Akt/ERK1/2-induced cell death of these tumor cells. These observations were further verified by the results from the implantation of both U87 and U118 cells into in vivo mouse. In conclusion, our findings suggest that artocarpin induces mitochondria-associated apoptosis of glioma cells, suggesting that artocarpine can be a potential chemotherapeutic agent for future GBM treatment.

17.
BMC Infect Dis ; 18(1): 194, 2018 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-29699503

RESUMO

BACKGROUND: Invasive candidiasis differs greatly between children and neonates. We aimed to investigate the different therapeutic approaches and their effects on treatment outcomes of these two groups. METHODS: Episodes of neonatal invasive candidiasis were compared with non-neonatal pediatric episodes during a 12-year cohort study. Clinical isolates were documented by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and DNA sequencing, and antifungal susceptibility testing was performed. RESULTS: A total of 342 episodes of invasive candidiasis (113 neonatal and 229 non-neonatal pediatric episodes) in 281 pediatric patients (96 neonates and 185 children) were identified. Candida albicans was the most common pathogen causing invasive candidiasis in neonates and children (47.8% vs. 44.1%). The antifungal susceptibility profiles were not significantly different between neonates and children. More neonates received amphotericin B as therapy, whereas more children received fluconazole or caspofungin. Compared with children, neonates had a significantly longer duration of fungemia, higher rates of septic shock (34.5% vs. 21.8%; P = 0.013), sepsis-attributable mortality (28.3% vs. 17.5%; P = 0.024) and in-hospital mortality (42.7% vs. 25.4%; P = 0.004) than children. Independent risk factors for treatment failure of invasive candidiasis were septic shock (odds ration [OR] 16.01; 95% confidence interval [CI] 7.64-33.56; P <  0.001), delayed removal of intravenous catheter (OR 6.78; 95% CI 2.80-17.41; P <  0.001), renal failure (OR 5.38; 95% CI 1.99-14.57; P = 0.001), and breakthrough invasive candidiasis (OR 2.99; 95% CI 1.04-8.67; P = 0.043). CONCLUSIONS: Neonatal invasive candidiasis has worse outcomes than non-neonatal pediatric candidiasis. Neonatologists and pediatricians must consider age-specific differences when developing treatment and prevention guidelines, or when interpreting studies of other age groups.


Assuntos
Antifúngicos/uso terapêutico , Candidíase Invasiva/tratamento farmacológico , Candidíase Invasiva/epidemiologia , Fungemia/microbiologia , Adolescente , Anfotericina B/uso terapêutico , Candida albicans/patogenicidade , Candidíase Invasiva/etiologia , Caspofungina/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Fluconazol/uso terapêutico , Fungemia/tratamento farmacológico , Fungemia/epidemiologia , Mortalidade Hospitalar , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Fatores de Risco , Taiwan/epidemiologia , Resultado do Tratamento
19.
Front Pharmacol ; 8: 819, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29184499

RESUMO

Aliskiren is a direct renin inhibitor that has been effective in anti-hypertension. We investigated whether aliskiren could improve the ischemia-induced cardiac injury and whether the autophagy was involved in this effect. A myocardial infarction (MI) model was created by the ligation of the left anterior coronary artery in C57J/BL6 mice. They were treated for 1, 3, 7, and 14 days with vehicle or aliskiren (25 mg/kg/day via subcutaneous injection). In vivo, the MI mice exhibited worse cardiac function by echocardiographic assessment and showed larger myocardial scarring by light microscopy, whereas aliskiren treatment reversed these effects, which were also associated with the changes in caspase-3 and Bcl-2 expression as well as in the number of apoptotic cells. Aliskiren increased autophagy, as demonstrated by LC3B-II expression and transmission electron microscopy. Furthermore, H9c2 cardiomyocytes were employed as an in vitro model to examine the effects of aliskiren on apoptosis and autophagy under oxygen glucose deprivation (OGD)-induced injury. Aliskiren significantly increased cell viability in a dose-dependent manner. The beneficial effects of aliskiren were associated with decreased apoptosis and mitochondrial membrane potential as well as increased autophagy via increased autophagosome formation. We also found that aliskiren-induced cardiomyocyte survival occurred via AMP-activated protein kinase (AMPK)-dependent autophagy. Taken together, these results indicated that aliskiren increased cardiomyocyte survival through increased autophagosomal formation and decreased apoptosis and necrosis via modulating AMPK expression. AMPK-dependent autophagy may represent a novel mechanism for aliskiren in ischemic cardiac disease therapy.

20.
Int J Mol Sci ; 18(7)2017 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-28703746

RESUMO

Melanoma is the most malignant form of skin cancer and is associated with a very poor prognosis. The aim of this study was to evaluate the apoptotic effects of cudraflavone C on A375.S2 melanoma cells and to determine the underlying mechanisms involved in apoptosis. Cell viability was determined using the MTT and real-time cytotoxicity assays. Flow cytometric evaluation of apoptosis was performed after staining the cells with Annexin V-FITC and propidium iodide. The mitochondrial membrane potential was evaluated using the JC-1 assay. Cellular ROS production was measured using the CellROX assay, while mitochondrial ROS production was evaluated using the MitoSOX assay. It was observed that cudraflavone C inhibited growth in A375.S2 melanoma cells, and promoted apoptosis via the mitochondrial pathway mediated by increased mitochondrial ROS production. In addition, cudraflavone C induced phosphorylation of MAPKs (p38, ERK, and JNK) and up-regulated the expression of apoptotic proteins (Puma, Bax, Bad, Bid, Apaf-1, cytochrome C, caspase-9, and caspase-3/7) in A375.S2 cells. Pretreatment of A375.S2 cells with MitoTEMPOL (a mitochondria-targeted antioxidant) attenuated the phosphorylation of MAPKs, expression of apoptotic proteins, and the overall progression of apoptosis. In summary, cudraflavone C induced apoptosis in A375.S2 melanoma cells by increasing mitochondrial ROS production; thus, activating p38, ERK, and JNK; and increasing the expression of apoptotic proteins. Therefore, cudraflavone C may be regarded as a potential form of treatment for malignant melanoma.


Assuntos
Apoptose/efeitos dos fármacos , Flavonas/farmacologia , Melanoma/enzimologia , Melanoma/patologia , Mitocôndrias/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Flavonas/química , Humanos , Melanoma/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Fosforilação/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA