RESUMO
Hepatic stellate cells (HSCs) are the main contributors to the development and progression of liver fibrosis. Parkin is an E3 ligase involved in mitophagy mediated by lysosomes that maintains mitochondrial homeostasis. Unfortunately, there is little information regarding the regulation of parkin by transforming growth factor-ß (TGF-ß) and its association with HSC trans-differentiation. This study showed that parkin is upregulated in fibrotic conditions and elucidated the underlying mechanism. Parkin was observed in the cirrhotic region of the patient liver tissues and visualized using immunostaining and immunoblotting of mouse fibrotic liver samples and primary HSCs. The role of parkin-mediated mitophagy in hepatic fibrogenesis was examined using TGF-ß-treated LX-2 cells with mitophagy inhibitor, mitochondrial division inhibitor 1. Parkin overexpression and its colocalization with desmin in human tissues were found. Increased parkin in fibrotic liver homogenates of mice was observed. Parkin was expressed more abundantly in HSCs than in hepatocytes and was upregulated under TGF-ß. TGF-ß-induced parkin was due to Smad3. TGF-ß facilitated mitochondrial translocation, leading to mitophagy activation, reversed by mitophagy inhibitor. However, TGF-ß did not change mitochondrial function. Mitophagy inhibitor suppressed profibrotic genes and HSC migration mediated by TGF-ß. Collectively, parkin-involved mitophagy by TGF-ß facilitates HSC activation, suggesting mitophagy may utilize targets for liver fibrosis.
Assuntos
Células Estreladas do Fígado , Fator de Crescimento Transformador beta , Animais , Humanos , Camundongos , Fígado/patologia , Cirrose Hepática/patologia , Mitofagia , Transdução de Sinais , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta1/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
Ultraviolet B (UVB) rays disrupt the skin by causing photodamage via processes such as reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, DNA damage, and/or collagen degradation. Castanopsis sieboldii is an evergreen tree native to the southern Korean peninsula. Although it is known to have antioxidant and anti-inflammatory effects, its protective effect against photodamage in keratinocytes has not been investigated. Thus, in the present study, we investigated the effect of 70% ethanol extract of C. sieboldii leaf (CSL3) on UVB-mediated skin injuries and elucidated the underlying molecular mechanisms. CSL3 treatment restored the cell viability decreased by UVB irradiation. Moreover, CSL3 significantly inhibited UVB- or tert-butyl hydroperoxide-mediated ROS generation in HaCaT cells. ER stress was inhibited, whereas autophagy was upregulated by CSL3 treatment against UVB irradiation. Additionally, CSL3 increased collagen accumulation and cell migration, which were decreased by UVB exposure. Notably, epigallocatechin gallate, the major component of CSL3, improved the cell viability decreased by UVB irradiation through regulation of ER stress and autophagy. Conclusively, CSL3 may represent a promising therapeutic candidate for the treatment of UVB-induced skin damage.
Assuntos
Queratinócitos , Pele , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular , Pele/metabolismo , Colágeno/metabolismo , Raios Ultravioleta/efeitos adversosRESUMO
Aberrant expression of CA125/MUC16 is associated with pancreatic ductal adenocarcinoma (PDAC) progression and metastasis. However, knowledge of the contribution of MUC16 to pancreatic tumorigenesis is limited. Here, we show that MUC16 expression is associated with disease progression, basal-like and squamous tumor subtypes, increased tumor metastasis, and short-term survival of PDAC patients. MUC16 enhanced tumor malignancy through the activation of AKT and GSK3ß oncogenic signaling pathways. Activation of these oncogenic signaling pathways resulted in part from increased interactions between MUC16 and epidermal growth factor (EGF)-type receptors, which were enhanced for aberrant glycoforms of MUC16. Treatment of PDAC cells with monoclonal antibody (mAb) AR9.6 significantly reduced MUC16-induced oncogenic signaling. mAb AR9.6 binds to a unique conformational epitope on MUC16, which is influenced by O-glycosylation. Additionally, treatment of PDAC tumor-bearing mice with either mAb AR9.6 alone or in combination with gemcitabine significantly reduced tumor growth and metastasis. We conclude that the aberrant expression of MUC16 enhances PDAC progression to an aggressive phenotype by modulating oncogenic signaling through ErbB receptors. Anti-MUC16 mAb AR9.6 blocks oncogenic activities and tumor growth and could be a novel immunotherapeutic agent against MUC16-mediated PDAC tumor malignancy.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antígeno Ca-125/genética , Carcinogênese/genética , Carcinoma Ductal Pancreático/tratamento farmacológico , Receptores ErbB/genética , Proteínas de Membrana/genética , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Animais , Anticorpos Monoclonais/farmacologia , Antígeno Ca-125/imunologia , Carcinogênese/imunologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/imunologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/imunologia , Camundongos , Metástase Neoplásica , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Transdução de SinaisRESUMO
A20 (also known as TNFAIP3) is a potent anti-inflammatory protein that suppresses many intracellular signaling pathways induced by inflammatory cytokines and bacterial and viral pathogens. The anti-inflammatory function of A20 depends on its modulation of or binding to polyubiquitin chains on key signaling proteins in the nuclear factor-κB (NF-κB) pathway. To test whether A20 can be used as therapeutic agent in these inflammatory diseases, we prepared a recombinant cell-penetrating form of A20 (TAT-A20) for intracellular delivery and examined its effect on tumor necrosis factor-α (TNFα)-induced NF-κB activation. We observed that TAT-A20 was effectively transduced into cells within 30 min, whereas A20 protein without TAT motive was not. TAT-A20 also inhibited NF-κB induction in fibroblasts stimulated with TNFα. These results suggest that increasing intracellular level of A20 can be an effective means to suppress NF-κB activation and treat inflammatory diseases.
Assuntos
Peptídeos Penetradores de Células/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/genética , Escherichia coli/genética , Células HEK293 , Humanos , Espaço Intracelular/metabolismo , Redobramento de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/química , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genéticaRESUMO
Pollen is an important cause of respiratory allergic reactions. As individual sanitation has improved, allergy risk has increased, and this trend is expected to continue due to climate change. Atmospheric pollen concentration is highly influenced by weather conditions. Regression analysis and modeling of the relationships between airborne pollen concentrations and weather conditions were performed to analyze and forecast pollen conditions. Traditionally, daily pollen concentration has been estimated using regression models that describe the relationships between observed pollen concentrations and weather conditions. These models were able to forecast daily concentrations at the sites of observation, but lacked broader spatial applicability beyond those sites. To overcome this limitation, an integrated modeling scheme was developed that is designed to represent the underlying processes of pollen production and distribution. A maximum potential for airborne pollen is first determined using the Weibull probability density function. Then, daily pollen concentration is estimated using multiple regression models. Daily risk grade levels are determined based on the risk criteria used in Korea. The mean percentages of agreement between the observed and estimated levels were 81.4-88.2 % and 92.5-98.5 % for oak and Japanese hop pollens, respectively. The new models estimated daily pollen risk more accurately than the original statistical models because of the newly integrated biological response curves. Although they overestimated seasonal mean concentration, they did not simulate all of the peak concentrations. This issue would be resolved by adding more variables that affect the prevalence and internal maturity of pollens.
Assuntos
Alérgenos/análise , Modelos Biológicos , Modelos Estatísticos , Pólen , Poluentes Atmosféricos/análise , Previsões , Humulus , Quercus , Análise de Regressão , República da Coreia , RiscoRESUMO
Despite the susceptibility to frequent intrinsic and extrinsic injuries, especially in the inner zone, the meniscus does not heal spontaneously owing to its poor vascularity. In this study, the effect of platelet-rich plasma (PRP), containing various growth factors, on meniscal mechanisms was examined under normal and post-traumatic inflammatory conditions. Isolated primary meniscal cells of New Zealand white (NZW) rabbits were incubated for 3, 10, 14 and 21 days with PRP(-), 10% PRP (PRP(+)), IL(+) or IL(+)PRP(+). The meniscal cells were collected and examined using reverse-transcription polymerase chain reaction (RT-PCR). Culture media were examined by immunoblot analyses for matrix metalloproteinases (MMP) catabolic molecules. PRP containing growth factors improved the cellular viability of meniscal cells in a concentration-dependent manner at Days 1, 4 and 7. However, based on RT-PCR, meniscal cells demonstrated dedifferentiation, along with an increase in type I collagen in the PRP(+) and in IL(+)PRP(+). In PRP(+), the aggrecan expression levels were lower than in the PRP(-) until Day 21. The protein levels of MMP-1 and MMP-3 were higher in each PRP group, i.e., PRP(+) and IL(+)PRP(+), at each culture time. A reproducible 2-mm circular defect on the meniscus of NZW rabbit was used to implant fibrin glue (control) or PRP in vivo. After eight weeks, the lesions in the control and PRP groups were occupied with fibrous tissue, but not with meniscal cells. This study shows that PRP treatment of the meniscus results in an increase of catabolic molecules, especially those related to IL-1α-induced inflammation, and that PRP treatment for an in vivo meniscus injury accelerates fibrosis, instead of meniscal cartilage.
Assuntos
Desdiferenciação Celular , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Meniscos Tibiais/metabolismo , Plasma Rico em Plaquetas/metabolismo , Agrecanas/genética , Agrecanas/metabolismo , Animais , Condrócitos/citologia , Colágeno/genética , Colágeno/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Meniscos Tibiais/citologia , CoelhosRESUMO
A substantial proportion of men with prostatic disease have an increased risk of bone loss. In the present study, we investigated the effects of Rubus coreanus Miquel (RCM) extracts on osteoporosis that occurs with N-methyl-N-nitrosourea (MNU)-induced prostatic hyperplasia. The rats used in this study were categorized into groups of healthy controls, rats treated with MNU, and rats treated with MNU and RCM. The rats were sacrificed after 10 weeks of RCM treatment, after which ultrasonography, serum biochemical tests, histopathological examinations, immunohistochemical analysis, and semi-quantitative reverse-transcription polymerase chain reaction analysis were performed. There were no marked differences in body weight gain and the size and weight of the prostate gland between the MNU group and the MNU and RCM group. However, treatment with RCM inhibited osteoclastic osteolysis and reduced dysplastic progress in the prostate gland, as observed by histopathological evaluation and by analyzing changes in the levels of bone regulatory factors. In addition, the group treated with MNU and RCM had higher expression levels of cannabinoid receptors-1, -2, and osteoprotegerin. These results indicate that the anti-osteoporotic effect of RCM in prostatic hyperplasia is attributable to the cannabinoid receptor-related upregulation of osteoblastogenesis and inhibition of prostatic hyperplasia. The results of the present study suggest that treatment with RCM may benefit osteoporotic patients with prostatic disease by simultaneously altering the activation of osteoblasts and osteoclasts.
Assuntos
Osteoporose/tratamento farmacológico , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Neoplasias da Próstata/complicações , Receptores de Canabinoides/metabolismo , Rubus/química , Envelhecimento , Animais , Modelos Animais de Doenças , Masculino , Metilnitrosoureia , Osteoporose/metabolismo , Fitoterapia/efeitos adversos , Próstata/patologia , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/patologia , RatosRESUMO
[Purpose] This study was performed to investigate the changes in the body balance index when spiral taping is applied to the neck and ankle. The findings are expected to serve as evidence of the usefulness of taping the neck instead of the ankle when ankle taping is not feasible in clinical practice. [Subjects and Methods] Twenty healthy male students at A university were enrolled in this study. Balance measurements were made under three conditions: no intervention, ankle intervention and neck intervention. Static balance was measured with subjects' eyes open and closed, and dynamic balance was measured with subjects' eyes closed. [Results] There were significant differences in dynamic balance assessed by the Overall Balance Index (OBI), and the Anteroposterior Balance Index (ABI) with subjects' eyes open when ankle or neck taping was applied compared to no intervention. The static balance (OBI) of subjects with eyes open showed significant differences from the no intervention condition in both the ankle and neck intervention. The static balance (OBI) with subjects' eyes closed also showed significant differences in both the ankle and neck interventions compared to the no intervention condition. [Conclusion] Our results indicate that neck taping stimulates the somatic senses around the neck and increase proprioception, resulting in balance improvement similar to that elicited by ankle taping. Further studies with larger sample sizes various experimental conditions should be performed to more systematically and objectively elucidate the effects of neck taping.
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In the present study, we determined whether two endocrine-disrupting chemicals (EDCs), triclosan (TCS) and octylphenol (OP), are able to alter the expression of two cell cycle regulators, cyclin D1 and p21, in both in vitro and mouse breast cancer models. In addition, we determined whether the stimulatory effects of OP or TCS on breast cancer progression may be associated with an estrogen receptor (ER)-mediated signaling pathway. Altered expressions of cyclin D1 and p21 were observed in MCF-7 human breast cancer cells treated with TCS and OP, which is linked to the G1/S transition of cell cycle, leading to cell proliferation. In a xenograft mouse model, breast tumor masses were established following exposure to TCS and OP for 8 weeks. In these animals, the tumor cells with BrdU-positive nuclei were increased by treatment with 17ß-estradiol (E2), OP, and TCS compared to that of a control (corn oil), suggesting that TCS and OP increase DNA synthesis during the S phase in tumor cells. Increased level of cyclin D1 protein by TCS and OP was also observed in vivo, implying that the effects of these EDCs possessing estrogenic activity alter the expression of genes related to cancer progression. It was of interest that the effects of TCS and OP were reversed by ICI 182,780, an ER antagonist, indicating that EDC-induced activities are mediated by an ER-dependent signaling pathway. Taken together, these results suggest that TCS and OP may promote breast cancer progression, via an ER-mediated signaling cascade.
Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Disruptores Endócrinos/efeitos adversos , Fenóis/efeitos adversos , Receptores de Estrogênio/metabolismo , Triclosan/efeitos adversos , Animais , Mama/efeitos dos fármacos , Mama/metabolismo , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/metabolismo , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/efeitos dos fármacosRESUMO
Anastomotic stricture is a typical complication of esophageal atresia surgery. Remote ischemic conditioning (RIC) has demonstrated multiorgan benefits, however, its efficacy in the esophagus remains unclear. This study aimed to investigate whether applying RIC after esophageal resection and anastomosis in rats could attenuate esophageal stricture and improve inflammation. Sixty-five male Sprague-Dawley rats were categorized into the following groups: controls with no surgery, resection and anastomosis only, resection and anastomosis with RIC once, and resection and anastomosis with RIC twice. RIC included three cycles of hind-limb ischemia followed by reperfusion. Inflammatory markers associated with the interleukin 6/Janus kinase/ signal transducer and activator of transcription 3 (IL-6/JAK/STAT3) and tumor necrosis factor-alpha/nuclear factor-κB (TNF-α/NF-kB) signaling pathways were evaluated with RNA and protein works. The RIC groups showed significantly lower stricture rates, lower inflammatory markers levels than the resection and anastomosis-only group. The RIC groups had significantly lower IL-6 and TNFa levels than the resection and anastomosis-only group, confirming the inhibitory role of remote ischemic conditioning in the IL-6/JAK/STAT3 and TNF-α/NF-kB signaling pathways. RIC after esophageal resection and anastomosis can reduce the inflammatory response, improving strictures at the esophageal anastomosis site, to be a novel noninvasive intervention for reducing esophageal anastomotic strictures.
Assuntos
Anastomose Cirúrgica , Modelos Animais de Doenças , Estenose Esofágica , Precondicionamento Isquêmico , Ratos Sprague-Dawley , Fator de Transcrição STAT3 , Animais , Masculino , Ratos , Precondicionamento Isquêmico/métodos , Estenose Esofágica/etiologia , Estenose Esofágica/prevenção & controle , Fator de Transcrição STAT3/metabolismo , NF-kappa B/metabolismo , Interleucina-6/metabolismo , Interleucina-6/sangue , Transdução de Sinais , Esôfago/cirurgia , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/sangue , Janus Quinases/metabolismoRESUMO
BACKGROUND/OBJECTIVES: Obesity is a major cause of metabolic disorders; to prevent obesity, research is ongoing to develop natural and safe ingredients with few adverse effects. In this study, we determined the anti-obesity effects of Rosa multiflora root extract (KWFD-H01) in 3T3-L1 adipocytes and Sprague-Dawley (SD) rats. MATERIALS/METHODS: The anti-obesity effects of KWFD-H01in 3T3-L1 adipocytes and SD rats were examined using various assays, including Oil Red O staining, gene expression analyses, protein expression analyses, and blood biochemical analyses. RESULTS: KWFD-H01 reduced intracellular lipid accumulation and inhibited the mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins (C/EBPα), sterol regulatory element-binding transcription factor 1 (SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) in 3T3-L1 cells. KWFD-H01 also reduced body weight, weight gain, and the levels of triglycerides, total and LDL-cholesterol, glucose, and leptin, while increasing high-density lipoprotein-cholesterol and adiponectin in SD rats. PPARγ, C/EBPα, SREBP-1c, ACC, and FAS protein expression was inhibited in the epididymal fat of SD rats. CONCLUSION: Overall, these results confirm the anti-obesity effects of KWFD-H01 in 3T3-L1 adipocytes and SD rats, indicating their potential as baseline data for developing functional health foods or pharmaceuticals to control obesity.
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Endocrine-disrupting chemicals (EDCs) are natural or synthetic compounds present in the environment which can interfere with hormone synthesis and normal physiological functions of male and female reproductive organs. Most EDCs tend to bind to steroid hormone receptors including the oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR). As EDCs disrupt the actions of endogenous hormones, they may induce abnormal reproduction, stimulation of cancer growth, dysfunction of neuronal and immune system. Although EDCs represent a significant public health concern, there are no standard methods to determine effect of EDCs on human beings. The mechanisms underlying adverse actions of EDC exposure are not clearly understood. In this review, we highlighted the toxicology of EDCs and its effect on human health, including reproductive development in males and females as shown in in vitro and in vivo models. In addition, this review brings attention to the toxicity of EDCs via interaction of genomic and non-genomic signalling pathways through hormone receptors.
Assuntos
Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Receptores Androgênicos/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Feminino , Regulação da Expressão Gênica , Aptidão Genética/efeitos dos fármacos , Hormônios Esteroides Gonadais/antagonistas & inibidores , Hormônios Esteroides Gonadais/genética , Hormônios Esteroides Gonadais/metabolismo , Humanos , Masculino , Ovário/citologia , Ovário/efeitos dos fármacos , Ovário/metabolismo , Receptores Androgênicos/metabolismo , Receptores de Estrogênio/agonistas , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/agonistas , Receptores de Progesterona/antagonistas & inibidores , Receptores de Progesterona/metabolismo , Reprodução/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Testículo/citologia , Testículo/efeitos dos fármacos , Testículo/metabolismoRESUMO
Focal adhesion kinase (FAK) consists of an N-terminal band 4.1; ezrin, radixin, moesin (FERM) domain; tyrosine kinase domain; and C-terminal FA targeting domain. Here we show that ectopically expressed FERM is largely located in the cytosolic fraction under quiescent conditions. We further found that this ectopically expressed FERM domain aggravates endothelial cell apoptosis triggered by 100 µM resveratrol, whereas FERM had no effect on apoptosis induced by TNF-α. We determined that resveratrol at low doses (<20 µM) promotes phosphorylation (S1177) of eNOS via an AMPK-dependent pathway. The presence of the FERM domain blocked this resveratrol-stimulated eNOS phosphorylation and NO production. Thus, the pro-apoptotic activity of cytosolic FERM domain is at least partially mediated by down-regulation of NO, a critical cell survival factor. Consistently, we found that the apoptosis induced by cytosolic FERM in the presence of resveratrol was reversed by an NO donor, SNAP. In conclusion, FERM located in the cytosolic fraction plays a pivotal role in aggravating cell apoptosis through diminishing NO production.
Assuntos
Apoptose/efeitos dos fármacos , Proteínas do Citoesqueleto/metabolismo , Células Endoteliais/efeitos dos fármacos , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Proteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Óxido Nítrico/antagonistas & inibidores , Estilbenos/farmacologia , Animais , Bovinos , Células Cultivadas , Proteínas do Citoesqueleto/genética , Citosol/metabolismo , Células Endoteliais/fisiologia , Proteína-Tirosina Quinases de Adesão Focal/genética , Proteínas de Membrana/genética , Proteínas dos Microfilamentos/genética , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , ResveratrolRESUMO
Following liver injuries, hepatic stellate cells (HSCs) express α-SMA. Mitogen activated protein kinase (MAPK) signaling pathways mediate α-SMA expression in distinct cell types. However, the regulation of α-SMA expression by MAPKs in HSCs has been rarely studied. We aimed to study the role of MAPKs in the activation of HSCs during liver fibrosis. Liver fibrosis of rats was induced by carbon tetrachloride. HSC-T6 cells, murine embryonic fibroblasts, JNK1(-/-) and JNK2(-/-) cells were used for in vitro studies. Immunohistochemistry and immunoblot analysis were used. We have found that the expression of JNK and α-SMA co-localized in HSCs during liver fibrosis, but ERK and p38 expressed in macrophages. The expression of α-SMA was up-regulated by JNK1 and JNK2 in non-stress condition. Under TGF-ß stimulation, however, the level α-SMA expression was increased by only JNK1, but not significantly changed by JNK2. We suggest that JNKs are responsible for α-SMA regulation, and especially JNK1 has a major role in up-regulation of α-SMA expression in HSCs under stress condition induced by TGF-ß during liver fibrosis.
Assuntos
Actinas/biossíntese , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Proteína Quinase 9 Ativada por Mitógeno/metabolismo , Animais , Western Blotting , Tetracloreto de Carbono/toxicidade , Imuno-Histoquímica , Imunoprecipitação , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Transfecção , Regulação para CimaRESUMO
Carbon-coated SnO2 nano-composite was synthesized by using a hydrothermal method in a one step process with sizes of 1 to 3 microm. The carbon-coated SnO2 nano-composite was easily obtained by changing firing atmosphere from air to argon (600 degrees C for 3 hours). The carbon-coating thickness and size of the SnO2 nanoparticles in carbon-coated SnO2 nano-composite were confirmed through a high-resolution transmission electron microscopy (HRTEM) as 40 and 5 nm, respectively. Carbon-coating and particle size affect to the capacity retention property. Carbon-coated and non carbon-coated samples were investigated as anode materials. It was confirmed that the non carbon-coated SnO2 nano-composite had a 718 mA h/g initial charge capacity, 91% reached to theoretical value of SnO2 (790 mA h/g), while the carbon-coated SnO2 nano-composite had an excellent capacity retention of 89.6% after 70 cycles (10.88% for non carbon-coated SnO2 nano-composite).
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Pinosylvin is a phenolic compound mainly found in the Pinus species. To determine the vascular functions of pinosylvin, we first examined both proliferation and apoptosis of bovine aortic endothelial cells (BAECs) in the presence of pinosylvin. When BAECs were treated with pinosylvin, etoposide- or starvation-induced apoptosis was shown to be significantly reduced. The anti-apoptotic effect of pinosylvin was mediated by inhibition of caspase-3. Moreover, pinosylvin was shown to activate endothelial nitric oxide synthetase (eNOS). At 1 pM, pinosylvin appeared to have a cell-proliferative effect in the endothelial cell. The pinosylvin-induced cell proliferation was declined by treatment with L-NAME, an eNOS inhibitor. Then, we found that pinosylvin had a stimulatory effect on cell migration and tube formation. These stimulatory effects suggest that pinosylvin is likely to act as a pro-angiogenic factor. Yet another effect of pinosylvin was inhibition of lipopolysaccharide-induced THP-1 cell adhesion to endothelial cells. Altogether, we propose that pinosylvin may be utilized as a phytotherapic agent for the prevention of cardiovascular inflammatory diseases.
Assuntos
Apoptose/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Óxido Nítrico/metabolismo , Estilbenos/farmacologia , Animais , Bovinos , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Óxido Nítrico Sintase Tipo III/metabolismoRESUMO
Platelets are involved in hemostasis, wound healing, and tumor growth. Autologous blood products are commonly used to facilitate healing in a variety of clinical surgery applications. Recently, it was shown that platelet-rich plasma (PRP) has more specific growth factors that participate in the healing process. This study investigated the expression of PRP growth factors and evaluated their potential role in the cartilage regeneration using primary isolated chondrocytes. PRP obtained from New Zealand White rabbit by low speed centrifugation. Extracted PRPs contained 6-10 × 10(6) platelet/µl and concentration of platelets was slightly variable. Primary isolated chondrocytes from the same rabbits were cultured and treated with 0.1-20% PRP. The cells were collected and examined by reverse transcription-polymerase chain reaction and cytochemical staining. The expression of sex determining region Y-box 9, transforming growth factor-beta, vascular endothelial growth factor, and chondromdulin-I was increased in chondrocyte cultures with 10% PRP by time-dependent manner. To maintain the integrity of the cartilage, the proteoglycan contents were also up-regulated from the mRNA of aggrecan and positive Safranin-O staining in PRP concentration- and time-dependent manner. PRP provides crucial growth factors related to chondrocyte proliferation and differentiation through time-sequential modulation. Controlled in vivo trials for cartilage regeneration are needed.
Assuntos
Condrócitos/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Plasma Rico em Plaquetas , Animais , Proliferação de Células , Forma Celular , Células Cultivadas , Colágeno Tipo II/metabolismo , Meios de Cultura , Regulação da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Coelhos , Transcrição GênicaRESUMO
CONTEXT: Since AMP-activated protein kinase (AMPK) activation in skeletal muscle of obese rodents stimulates fatty acid oxidation, it is reasonable to hypothesize that pharmacological activation of AMPK might be of therapeutic benefit in obesity. OBJECTIVE: To investigate the effects of the traditional Korean anti-obesity drug GGEx18, a mixture of three herbs, Laminaria japonica Aresch (Laminariaceae), Rheum palmatum L. (Polygonaceae), and Ephedra sinica Stapf (Ephedraceae), on obesity and the involvement of AMPK in this process. MATERIALS AND METHODS: After high fat diet-induced obese mice were treated with GGEx18, we studied the effects of GGEx18 on body weight, fat mass, skeletal muscle lipid accumulation, and the expressions of AMPK, peroxisome proliferator-activated receptor ά (PPARα), and PPARα target genes. The effects of GGEx18 and/or the AMPK inhibitor compound C on lipid accumulation and expression of the above genes were measured in C2C12 skeletal muscle cells. RESULTS: Administration of GGEx18 to obese mice for 9 weeks significantly (p < 0.05) decreased body and adipose tissue weights compared with obese control mice (p < 0.05). Lipid accumulation in skeletal muscle was inhibited by GGEx18. GGEx18 significantly (p < 0.05) increased skeletal muscle mRNA levels of AMPKα1 and AMPKα2 as well as PPARα and its target genes. Consistent with the in vivo data, GGEx18 inhibited lipid accumulation, and similar activation of genes was observed in GGEx18-treated C2C12 cells. However, compound C inhibited these effects in C2C12 cells. DISCUSSION AND CONCLUSION: These results suggest that GGEx18 improves obesity through skeletal muscle AMPK and AMPK-stimulated expression of PPARα and its target enzymes for fatty acid oxidation.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Fármacos Antiobesidade/farmacologia , Ephedra sinica , Laminaria , Músculo Esquelético/efeitos dos fármacos , Obesidade/tratamento farmacológico , PPAR alfa/metabolismo , Preparações de Plantas/farmacologia , Rheum , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/genética , Adiposidade/efeitos dos fármacos , Animais , Fármacos Antiobesidade/química , Linhagem Celular , Dieta Hiperlipídica , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/enzimologia , Obesidade/enzimologia , Obesidade/etiologia , Obesidade/genética , Obesidade/fisiopatologia , PPAR alfa/genética , Extratos Vegetais , Preparações de Plantas/química , Plantas Medicinais , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Redução de Peso/efeitos dos fármacosRESUMO
UNLABELLED: Senescence marker protein 30 (SMP30), an important aging marker molecule that is highly expressed in the liver, has been known to protect hepatocytes from apoptosis by the synthesis of vitamin C. To explore the function of SMP30 in liver fibrosis, the effect of SMP30 deficiency on liver fibrosis was investigated in SMP30 knockout (KO) mice. Moreover, the in vivo results were further confirmed by way of hepatic stellate cell (HSC) isolation. We demonstrated that carbon tetrachloride (CCl(4))-induced liver fibrosis and the nuclear translocation of p-Smad2/3, the immediate downstream of transforming growth factor beta (TGF-beta), were significantly inhibited in the liver of SMP30 KO mice compared with wildtype (WT) mice. We also confirmed that both WT and SMP30 KO HSCs did not express SMP30. Finally, we further confirmed that up-regulation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) caused by a lack of vitamin C was the pivotal factor in the mechanisms for attenuated liver fibrosis of SMP30 KO mice, and feeding with vitamin C restored CCl(4)-induced liver fibrosis in SMP30 KO mice. CONCLUSION: Vitamin C deficiency by SMP30 depletion attenuated liver fibrosis by way of up-regulated PPAR-gamma expression in SMP30 KO mice. Our results provide, for the first time, the possible mechanisms underlying inhibition of HSC activation associated with vitamin C and PPAR-gamma up-regulation in liver fibrosis of SMP30 KO mice.
Assuntos
Ácido Ascórbico/farmacologia , Proteínas de Ligação ao Cálcio/deficiência , Células Estreladas do Fígado/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Cirrose Hepática/prevenção & controle , PPAR gama/metabolismo , Animais , Ácido Ascórbico/sangue , Proteínas de Ligação ao Cálcio/biossíntese , Intoxicação por Tetracloreto de Carbono/patologia , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Knockout , Proteínas Smad/metabolismoRESUMO
Salt stress is a major constraint of crop productivity because it reduces yield and limits the expansion of agriculture. This study investigated salt tolerance in 26 cultivars of cut lilies (Lilium hybrids) by examining the effect of salt stress on the growth and morphological characteristics of flowers and leaves and their physiological properties (chlorophyll a fluorescence). Salt stress significantly affected the growth and development of cut lilies. Canonical discriminant analysis indicates that the middle leaf width, number of flowers, first flower diameter, petal width, and chlorophyll a fluorescence were correlated with salt stress, whereas plant height, the middle leaf length, days to flowering, and sepal width were less affected by the stress. The cultivars examined were divided into three groups: Group 1 included the salt-sensitive cultivars, which failed to develop normal flowers; Group 2 included cultivars sensitive to salt stress but tolerant to osmotic stress; and Group 3 was the salt-tolerant group, which developed commercially valuable flowers. In conclusion, the cultivars contained a variable range of cut flower characteristics and growth traits that can be employed for lily breeding programs and as material for molecular mechanisms and signaling networks under salt stress.