RESUMO
Side streams and byproducts of food are established sources of natural ingredients in cosmetics. In the present study, we obtained upcycled low-molecular-weight anionic peptides (LMAPs) using byproducts of the post-yuzu-juicing process by employing an enzyme derived from Bacillus sp. For the first time, we isolated anionic peptides less than 500 Da in molecular weight from Citrus junos TANAKA seeds via hydrolysis using this enzyme. The protective effect of LMAPs against UVR-induced photoaging was evaluated using a reconstructed skin tissue (RST) model and keratinocytes. The LMAPs protected the keratinocytes by scavenging intracellular reactive oxygen species and by reducing the levels of paracrine cytokines (IL-6 and TNF-α) in UVR (UVA 2 J/cm2 and UVB 15 mJ/cm2)-irradiated keratinocytes. Additionally, the increase in melanin synthesis and TRP-2 expression in RST caused by UVR was significantly inhibited by LMAP treatment. This treatment strongly induced the expression of filaggrin and laminin-5 in UVR-irradiated RST. It also increased type I collagen expression in the dermal region and in fibroblasts in vitro. These results suggest that a hydrolytic system using the enzyme derived from Bacillus sp. can be used for the commercial production of LMAPs from food byproducts and that these LMAPs can be effective ingredients for improving photoaging-induced skin diseases.
Assuntos
Citrus , Envelhecimento da Pele , Dermatopatias , Pele/metabolismo , Citocinas/metabolismo , Dermatopatias/metabolismo , Raios Ultravioleta/efeitos adversos , Fibroblastos/metabolismoRESUMO
Blackberries (Rubus fruticosus), which are known to include a variety of bioactive substances, have been extensively studied for their antioxidant properties. Blackberries possess multiple health beneficial effects, including anti-inflammation, anti-atherosclerosis, anti-tumor and immunomodulatory activity. However, the potential biological effects and precise molecular mechanisms of the fermented extracts remain largely unexplored. In this research, we demonstrate the effect of blackberries fermented with Lactobacillus for addressing obesity. We investigated the effect of blackberries fermented by Lactobacillus on mice fed a high-fat (60% kcal) diet for 12 weeks. Fermented blackberry administration reduced the body weight and epididymal fat caused by a high-fat diet compared to the obese group. The triglyceride and total cholesterol, which are blood lipid indicators, and the levels of leptin, which is an insulin resistance indicator, were significantly increased in the obese group but were significantly decreased in the fermented blackberries-treated group. Additionally, the expression of adipogenesis marker proteins, such as CEBPα, PPAR-γ and SREBP-1, was significantly increased in the obese group, whereas it was decreased in the fermented blackberries-treated group. These results suggest that fermented blackberries have a protective effect against high-fat-diet-induced obesity by inhibiting adipogenesis and are a potential candidate for the treatment of obesity.
Assuntos
Adipogenia , Fármacos Antiobesidade , Dieta Hiperlipídica , Fermentação , Lactobacillus plantarum , Obesidade , PPAR gama , Rubus , Transdução de Sinais , Animais , Adipogenia/efeitos dos fármacos , Rubus/química , Camundongos , Obesidade/metabolismo , Fármacos Antiobesidade/farmacologia , Masculino , Dieta Hiperlipídica/efeitos adversos , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Camundongos Endogâmicos C57BL , Leptina/metabolismo , Leptina/sangue , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/genética , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Peso Corporal/efeitos dos fármacosRESUMO
Cervi cornu extracts have been used in traditional medicine for the treatment of various disorders, including osteoporosis. However, since it is not easy to separate the active ingredients, limited research has been conducted on their functional properties. In this study, we extracted the low-molecular-weight (843 Da) collagen NP-2007 from cervi cornu by enzyme hydrolyzation to enhance absorption and evaluated the therapeutic effect in monosodium iodoacetate-induced rat osteoarthritis (OA) model. NP-2007 was orally administered at 50, 100, and 200 mg/kg for 21 days. We showed that the production of matrix metalloproteinase-2, -3, and -9, decreased after NP-2007 treatment. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and prostaglandin E2 were also reduced after treatment of NP-2007. Furthermore, the administration of NP-2007 resulted in effective preservation of both the synovial membrane and knee cartilage and significantly decreased the transformation of fibrous tissue. We verified that the treatment of NP-2007 significantly reduced the production of nitric oxide and pro-inflammatory cytokines including TNF-α, IL-1ß, and IL-6 in lipopolysaccharides-stimulated RAW 264.7 cells by regulation of the NF-kB and MAPK signaling pathways. This study indicates that NP-2007 can alleviate symptoms of osteoarthritis and can be applied as a novel treatment for OA treatment.
Assuntos
Cornus , Osteoartrite , Ratos , Animais , Metaloproteinase 2 da Matriz , Interleucina-6/farmacologia , Osteoartrite/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Colágeno/farmacologia , Condrócitos/metabolismoRESUMO
BACKGROUND: It is necessary to examine the level of perception, knowledge and attitudes of the medical staff for advance medical directives, which are practical alternatives to good practice for end-of-life care in the actual medical field. PURPOSE: This study was conducted to determine the degree of perception, knowledge and attitude of cancer hospital medical staff about advance medical directives, and to confirm the relationship between them. It also explored their experiences with advance medical directives. METHODS: This study used a convergent design to collect quantitative and qualitative data separately in the mixed methodology. This design adheres to the STROBE guidelines. Participants were a total of 140 subjects (70 doctors and 70 nurses) with more than 3 years and considered to have sufficient experience related to the study purpose. Focus group participants were a total 19 persons (9 doctors and 10 nurses). RESULTS: Mean score for perception was 35.40, which indicates lower perception when compared to the median value (37.50 points). Perception of advance medical directives had significant, positive relations with attitude of advance medical directives (p = .032). The perception on attitude of advance medical directives factor was significantly influencing (p = .021). As a result of the analysis based on qualitative research questions, six subjects and 11 categories were created by deriving meaningful sentences from the statements. CONCLUSION: This study suggests that the perception of medical professionals about advance medical directives has a positive correlation with attitudes, as well as a causal relationship. RELEVANCE TO CLINICAL PRACTICE: Based on the finding from this study, concrete strategies and interventions to improve the perception of advance medical directives among cancer hospital medical staff are needed.
Assuntos
Atitude do Pessoal de Saúde , Neoplasias , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Percepção , Recursos Humanos em HospitalRESUMO
BACKGROUND: Alcohol abuse and alcoholism lead to alcohol liver disease such as alcoholic fatty liver. Parkin is a component of the multiprotein E3 ubiquitin ligase complex and is associated with hepatic lipid accumulation. However, the role of parkin in ethanol-induced liver disease has not been reported. Here, we tested the effect of parkin on ethanol-induced fatty liver in parkin knockout (KO) mice with chronic ethanol feeding. METHODS: Male wild type (WT) and parkin KO mice (10-12 weeks old, n = 10) were fed on a Lieber-DeCarli diet containing 6.6% ethanol for 10 days. Liver histological, biochemical, and gene-expression studies were performed. RESULTS: Parkin KO mice exhibited lower hepatosteatosis after ethanol consumption. Because several studies reported that ß-catenin is a critical factor in ethanol metabolism and protects against alcohol-induced hepatosteatosis, we investigated whether parkin changes ß-catenin accumulation in the liver of ethanol-fed mice. Our results show that ß-catenin was greatly accumulated in the livers of ethanol-fed parkin KO mice compared to ethanol-fed WT mice, and that parkin binds to ß-catenin and promotes its degradation it by ubiquitination. Moreover, the ß-catenin inhibitor IWR-1 abrogated the attenuation of ethanol-induced hepatic lipid accumulation by parkin deficiency in the livers of parkin KO mice and parkin siRNA-transfected human hepatic cell line. CONCLUSIONS: Parkin deficiency prevents ethanol-induced hepatic lipid accumulation through promotion of ß-catenin signaling by failure of ß-catenin degradation.
Assuntos
Lipídeos/química , Ubiquitina-Proteína Ligases/metabolismo , beta Catenina/metabolismo , Animais , Etanol/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais , Ubiquitina-Proteína Ligases/deficiênciaRESUMO
We investigated whether bakuchiol, an analog of resveratrol enhances the apoptosis ability of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in cancer cells. Bakuchiol enhanced expression of cell death receptor (DR) in TRAIL-sensitive and -resistant colon cancer cells in a dose-dependent manner. A combination of bakuchiol with TRAIL significantly inhibited cell growth of TRAIL sensitive HCT116 and TRAIL resistant HT-29 cells. The expression of TRAIL receptors; DR4 and DR5 was significantly increased by treatment of bakuchiol, however, the expression of survival proteins (e.g., cFLIP, survivin, XIAP and Bcl2) was suppressed. Moreover, the expression of apoptosis related proteins such as cleaved caspase-3, -8, -9 and PARP was increased by combination treatment of bakuchiol and TRAIL. Depletion of DR4 or DR5 by small interfering RNA significantly reversed the cell growth inhibitory effects of bakuchiol in HCT116 and HT-29 cells. Pretreatment with the c-Jun N-terminal kinase (JNK) inhibitor SP600125 and the reactive oxygen species (ROS) scavenger N-acetylcysteine reduced the bakuchiol induced cell growth inhibitory effects. The collective results suggest that bakuchiol facilitates TRAIL-induced apoptosis in colon cancer cells through up-regulation of the TRAIL receptors; DR4 and DR5 via ROS/JNK pathway signals.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , MAP Quinase Quinase 4/metabolismo , Fenóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Receptores de Morte Celular/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Regulação para Baixo/efeitos dos fármacos , Células HT29 , Humanos , Fenóis/isolamento & purificação , Psoralea/química , Regulação para Cima/efeitos dos fármacosRESUMO
Naphthofuran compounds have been known to regulate HNF 4α which is associated with proliferation, progression and metastasis of HCC. In this study, we investigated whether N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2,3-dihydronaphtho[1,2-b]furan-2-carboxamide (NHDC), a novel synthetic naphthofuran compound inhibits liver tumor growth through activation of HNF 4α. Treatment with different concentrations (1-10.8 µM) of NHDC for various periods (0-72 h) inhibited liver cancer cells (HepG2, Hep3B) growth as well as colony formation followed by induction of apoptosis in a concentration dependent manner. NHDC also induced expression of the apoptosis regulating genes as well as inhibiting the action of STAT3. These inhibitory effects were associated with enhancement of expression and DNA binding activity of HNF 4α. In vivo study confirmed that liver tumor growth was prevented with NHDC (5 mg/kg), and its effect was also related with inhibition of STAT3 pathway through enhancement of expression and DNA binding activity of HNF 4α. Moreover, siRNA of HNF 4α abolished NHDC-induced cell growth inhibition as well as DNA binding activity and phosphorylation of STAT3. Pull down assay docking prediction analysis proved that NHDC directly binds to hydrophobic fatty acid ligand binding site of HNF 4α. A novel naphthofuran compound, NHDC inhibited liver tumor growth by inactivating of STAT3 through direct biding to HNF 4α.
Assuntos
Antineoplásicos/administração & dosagem , Furanos/administração & dosagem , Fator 4 Nuclear de Hepatócito/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Naftalenos/administração & dosagem , Naftóis/administração & dosagem , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Furanos/síntese química , Furanos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Camundongos , Naftalenos/síntese química , Naftalenos/farmacologia , Naftóis/síntese química , Naftóis/farmacologia , Fator de Transcrição STAT3/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Nearly 7-10 million people are living with Alzheimer's disease (AD) worldwide. Senile plaques composed of ß-amyloid (Aß) are a pathological hallmark of Alzheimer's disease. Presenilin 2 (PS2) mutations increase Aß generation in the brains of AD patients. The Aß is generated through the sequential cleavage of amyloid precursor protein by ß- and γ-secretases. Additionally, increasing evidences suggest that estrogen can reduce the development of AD via regulation of ß-secretases activity and beta-site APP-cleaving enzyme (BACE1) expression. But the underlying correlation mechanism of Aß generation by PS2 mutations and estrogen remains to be clarified. To investigate the anti-amyloidogenesis effect of estrogen in a PS2 mutative condition, we examined memory impairment in ovariectomized PS2 mutation (N141I) mice in which cognitive function was assessed by the Morris water maze test and passive avoidance test. In addition, Western blot analysis, immunostaining, immunofluorescence staining, ELISA and enzyme activity assays were used to examine the degree of Aß deposition in the brains. In the present study, Aß accumulated more in the ovariectomized PS2 mutant mice brain, and greatly worsened memory impairment and glial activation as well as neurogenic inflammation. In parallel with increased memory impairment, activity of ß-secretase and expression of the BACE1 increased inovariectomized PS2 mutant mice. Much higher activity of NF-κB was observed by EMSA in ovariectomized PS2 mutant mice. In addition, the Aß level was decreased by treatment of ß-estradiol through inhibiting BACE1 expression in PS2 transfacted PC12 cells. These results suggest that mutation of PS2 can lead to NF-κB mediate amyloidogensis, and this effect can be amplified by the absence of estrogen.
Assuntos
Secretases da Proteína Precursora do Amiloide/metabolismo , Amiloide/biossíntese , Estrogênios/deficiência , Transtornos da Memória/metabolismo , NF-kappa B/metabolismo , Presenilina-2/metabolismo , Doença de Alzheimer/metabolismo , Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Cognição , Estrogênios/metabolismo , Feminino , Masculino , Transtornos da Memória/genética , Camundongos , Camundongos Endogâmicos ICR , Camundongos Transgênicos , Placa Amiloide/metabolismo , Presenilina-2/genética , Transdução de SinaisRESUMO
Approximately, 7-10 million people in the world suffer from Parkinson's disease (PD). Recently, increasing evidence has suggested the protective effect of estrogens against nigrostriatal dopaminergic damage in PD. In this study, we investigated whether estrogen affects 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral impairment in estrogen receptor alpha (ERα)-deficient mice. MPTP (15mg/kg, four times with 1.5-h interval)-induced dopaminergic neurodegeneration was evaluated in ERα wild-type (WT) and knockout (KO) mice. Larger dopamine depletion, behavioral impairments (Rotarod test, Pole test, and Gait test), activation of microglia and astrocytes, and neuroinflammation after MPTP injection were observed in ERα KO mice compared to those in WT mice. Immunostaining for tyrosine hydroxylase (TH) after MPTP injection showed fewer TH-positive neurons in ERα KO mice than WT mice. Levels of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC, metabolite of dopamine) were also lowered in ERα KO mice after MPTP injection. Interestingly, a higher immunoreactivity for monoamine oxidase (MAO) B was found in the substantia nigra and striatum of ERα KO mice after MPTP injection. We also found an increased activation of p38 kinase (which positively regulates MAO B expression) in ERα KO mice. In vitro estrogen treatment inhibited neuroinflammation in 1-methyl-4-phenyl pyridium (MPP+)-treated cultured astrocyte cells; however, these inhibitory effects were removed by p38 inhibitor. These results indicate that ERα might be important for dopaminergic neuronal survival through inhibition of p38 pathway.
Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Neurônios Dopaminérgicos/fisiologia , Receptor alfa de Estrogênio/genética , Estrogênios/fisiologia , Degeneração Neural/genética , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Doença de Parkinson/fisiopatologia , Substância Negra/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologiaRESUMO
C-C chemokine receptor 5 (CCR5) regulates leukocyte chemotaxis and activation, and its deficiency exacerbates development of nephritis. Therefore, we investigated the role of CCR5 during lipopolysaccharide (LPS)-induced acute kidney injury. CCR5-deficient (CCR5-/-) and wild-type (CCR5+/+) mice, both aged about 10 months, had acute renal injury induced by intraperitoneal injection of LPS (10 mg/kg). Compared with CCR5+/+ mice, CCR5-/- mice showed increased mortality and renal injury, including elevated creatinine and blood urea nitrogen levels, following LPS challenge. Compared to CCR5+/+ mice, CCR5-/- mice also exhibited greater increases in the serum concentrations of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß following LPS challenge. Furthermore, infiltration of macrophages and neutrophils, expression of intracellular adhesion molecule (ICAM)-1, and the number of apoptotic cells were more greatly increased by LPS treatment in CCR5-/- mice than in CCR5+/+ mice. The concentrations of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ß were also significantly increased in the kidney of CCR5-/- mice after LPS challenge. Moreover, primary kidney cells from CCR5-/- mice showed greater increases in TNF-α production and p38 MAP kinase activation following treatment with LPS compared with that observed in the cells from CCR5+/+ mice. LPS-induced TNF-α production and apoptosis in the primary kidney cells from CCR5-/- mice were inhibited by treatment with p38 MAP kinase inhibitor. These results suggest that CCR5 deficiency increased the production of TNF-α following LPS treatment through increased activation of the p38 pathway in the kidney, resulting in renal apoptosis and leukocyte infiltration and led to exacerbation of LPS-induced acute kidney injury.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Rim/metabolismo , Lipopolissacarídeos , Receptores CCR5/deficiência , Injúria Renal Aguda/genética , Injúria Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Células Cultivadas , Creatinina/sangue , Modelos Animais de Doenças , Predisposição Genética para Doença , Mediadores da Inflamação/sangue , Rim/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Knockout , Infiltração de Neutrófilos/efeitos dos fármacos , Fenótipo , Receptores CCR5/genética , Transdução de Sinais , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
We previously found that snake venom toxin inhibits nuclear factor kappa B (NF-κB) activity in several cancer cells. NF-κB is implicated in cancer cell growth and chemoresistance. In our present study, we investigated whether snake venom toxin (SVT) inhibits NF-κB, thereby preventing human cervical cancer cell growth (Ca Ski and C33A). SVT (0-12 µg/ml) inhibited the growth of cervical cancer cells by the induction of apoptotic cell death. These inhibitory effects were associated with the inhibition of NF-κB activity. However, SVT dose dependently increased the expression of death receptors (DRs): DR3, DR5 and DR downstream pro-apoptotic proteins. Exploration of NF-κB inhibitor (Phenylarsine oxide, 0.1 µM) synergistically further increased SVT-induced DR3 and DR5 expressions accompanied with further inhibition of cancer cells growth. Moreover, deletion of DR3 and DR5 by small interfering RNA significantly abolished SVT-induced cell growth inhibitory effects, as well as NF-κB inactivation. Using TNF-related apoptosis-inducing ligand resistance cancer cells (A549 and MCF-7), we also found that SVT enhanced the susceptibility of chemoresistance of these cancer cells through down-regulation of NF-κB, but up-regulation of DR3 and DR5. In vivo study also showed that SVT (0.5 and 1 mg/kg) inhibited tumor growth accompanied with inactivation of NF-κB. Thus, our present study indicates that SVT could be applicable as an anticancer agent for cervical cancer, or as an adjuvant agent for chemoresistant cancer cells.
Assuntos
NF-kappa B/antagonistas & inibidores , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Membro 25 de Receptores de Fatores de Necrose Tumoral/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Venenos de Víboras/farmacologia , Animais , Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Membro 25 de Receptores de Fatores de Necrose Tumoral/genética , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Flavonoids are a diverse family of natural phenolic compounds commonly found in fruits and vegetables. Epidemiologic studies showed that flavonoids also reduce the risk of colon cancer. Tectochrysin is one of the major flavonoids of Alpinia oxyphylla Miquel. However, the anti-cancer effects and the molecular mechanisms of tectochrysin in colon cancer cells have not yet been reported. We investigated whether tectochrysin could inhibit colon cancer cell growth at 1, 5, 10 µg/ml. In in vivo study, we injected a tectochrysin treatment dose of 5 mg/kg to each mouse. RESULTS: Tectochrysin suppressed the growth of SW480 and HCT116 human colon cancer cells. The expression of DR3, DR4 and Fas were significantly increased, and pro-apoptotic proteins were also increased. Tectochrysin treatment also inhibited activity of NF-κB. A docking model indicated that tectochrysin binds directly to the p50 unit. In in vivo, tumor weights and volumes in mice were reduced when treated with tectochrysin. Tectochrysin leads to apoptotic cell death in colon cancer cells through activation of death receptors expression via the inhibition of NF-κB. CONCLUSIONS: Tectochrysin can be a useful agent for the treatment of colon cancer cell growth as well as an adjuvant agent for chemo-resistant cancer cells growth.
Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Flavonoides/farmacologia , NF-kappa B/metabolismo , Receptores de Morte Celular/metabolismo , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Flavonoides/química , Células HCT116 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Interferente Pequeno/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Receptor fas/metabolismoRESUMO
BACKGROUND: Accumulation of beta-amyloid and neuroinflammation trigger Alzheimer's disease. We previously found that lipopolysaccharide (LPS) caused neuroinflammation with concomitant accumulation of beta-amyloid peptides leading to memory loss. A variety of anti-inflammatory compounds inhibiting nuclear factor kappaB (NF-κB) activation have showed efficacy to hinder neuroinflammation and amyloidogenesis. We also found that bee venom (BV) inhibits NF-κB. METHODS: A mouse model of LPS-induced memory loss used administration of BV (0.8 and 1.6 µg/kg/day, i.p.) to ICR mice for 7 days before injection of LPS (2.5 mg/kg/day, i.p.). Memory loss was assessed using a Morris water maze test and passive avoidance test. For in vitro study, we treated BV (0.5, 1, and 2 µg/mL) to astrocytes and microglial BV-2 cells with LPS (1 µg/mL). RESULTS: We found that BV inhibited LPS-induced memory loss determined by behavioral tests as well as cell death. BV also inhibited LPS-induced increases in the level of beta-amyloid (Aß), ß-and γ-secretases activities, NF-κB and its DNA-binding activity and expression of APP, and BACE1 and neuroinflammation proteins (COX-2, iNOS, GFAP and IBA-1) in the brain and cultured cells. In addition, pull-down assay and molecular modeling showed that BV binds to NF-κB. CONCLUSIONS: BV attenuates LPS-induced amyloidogenesis, neuroinflammation, and therefore memory loss via inhibiting NF-κB signaling pathway. Thus, BV could be useful for treatment of Alzheimer's disease.
Assuntos
Venenos de Abelha/farmacologia , Venenos de Abelha/uso terapêutico , Lipopolissacarídeos/efeitos adversos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/prevenção & controle , NF-kappa B/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Ciclo-Oxigenase 2/metabolismo , Proteína Glial Fibrilar Ácida , Técnicas In Vitro , Inflamação/induzido quimicamente , Inflamação/fisiopatologia , Inflamação/prevenção & controle , Lipopolissacarídeos/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/fisiopatologia , Camundongos , Camundongos Endogâmicos ICR , Microglia/efeitos dos fármacos , Microglia/metabolismo , Modelos Animais , NF-kappa B/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Transdução de Sinais/fisiologiaRESUMO
Xylitol is a widely used anti-caries agent that has anti-inflammatory effects. We have evaluated the potential of xylitol in cancer treatment. It's effects on cell proliferation and cytotoxicity were measured by MTT assay and LDH assay. Cell morphology and autophagy were examined by immunostaining and immunoblotting. Xylitol inhibited cell proliferation in a dose-dependent manner in these cancer cells: A549, Caki, NCI-H23, HCT-15, HL-60, K562, and SK MEL-2. The IC50 of xylitol in human gingival fibroblast cells was higher than in cancer cells, indicating that it is more specific for cancer cells. Moreover, xylitol induced autophagy in A549 cells that was inhibited by 3-methyladenine, an autophagy inhibitor. These results indicate that xylitol has potential in therapy against lung cancer by inhibiting cell proliferation and inducing autophagy of A549 cells.
Assuntos
Autofagia/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Xilitol/toxicidade , Linhagem Celular Tumoral , Técnicas Citológicas , Formazans/análise , Humanos , L-Lactato Desidrogenase/análise , Sais de Tetrazólio/análiseRESUMO
With the development of flexible mobile devices, flexible Li-ion batteries have naturally received much attention. Previously, all reported flexible components have had shortcomings related to power and energy performance. In this research, in order to overcome these problems while maintaining the flexibility, honeycomb-patterned Cu and Al materials were used as current collectors to achieve maximum adhesion in the electrodes. In addition, to increase the energy and power multishelled LiNi0.75Co0.11Mn0.14O2 particles consisting of nanoscale V2O5 and LixV2O5 coating layers and a LiδNi0.75-zCo0.11Mn0.14VzO2 doping layer were used as the cathode-anode composite (denoted as PNG-AES) consisting of amorphous Si nanoparticles (<20 nm) loaded on expanded graphite (10 wt %) and natural graphite (85 wt %). Li-ion cells with these three elements (cathode, anode, and current collector) exhibited excellent power and energy performance along with stable cycling stability up to 200 cycles in an in situ bending test.
RESUMO
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered a promising agent for medical applications because it induces apoptosis selectively in a variety of cancer cells without toxicity to normal human cells. However, its therapeutic potential has been limited by the existence of several cancer cells with TRAIL resistance. TRAIL resistance results from a variety of mechanisms, which occur at various points in the cellular signaling pathways. In this study, we demonstrate that ALS2CR7 (CDK15) can mediate resistance to TRAIL. We also demonstrate that cell viability of TRAIL sensitive HCT116 and MDA-MB-231 cells increased after TRAIL treatment in ALS2CR7 transfected cancer cells compared with vector transfected cancer cells. Furthermore, cell viability was decreased by TRAIL treatment after knockdown with ALS2CR7 siRNA in TRAIL resistant HT29 and MCF-7 cells. We also show that the activated form of apoptotic proteins such as caspase-3, -8 and -9 and PARP increased after TRAIL treatment in the control group, but decreased in the ALS2CR7 transfected group. The expression of survival proteins such as bcl2 and survivin in TRAIL sensitive cancer cells increased in the ALS2CR7 transfected group, but decreased in TRAIL resistant cancer cells treated with ALS2CR7 siRNA. Other survival proteins such as FLIP and XIAP were not affected. ALS2CR7 appears to bind with only survivin, and not bcl2. The phospho-survivin (Thr34) critical in drug resistance was increased by transfection with ALS2CR7, but the expression of death receptors such as DR4 and DR5 was not affected. ALS2CR7 did not bind with any of the death receptors in our study. In summary, our results suggest that ALS2CR7 confers TRAIL resistance to cancer cells via phosphorylation of survivin.
Assuntos
Apoptose/efeitos dos fármacos , Quinases Ciclina-Dependentes/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/administração & dosagem , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Células HT29 , Humanos , SurvivinaRESUMO
GeO2/Ge/C anode material synthesized using a simple method involving simultaneous carbon coating and reduction by acetylene gas is composed of nanosized GeO2/Ge particles coated by a thin layer of carbon, which is also interconnected between neighboring particles to form clusters of up to 30 µm. The GeO2/Ge/C composite shows a high capacity of up to 1860 mAh/g and 1680 mAh/g at 1 C (2.1 A/g) and 10 C rates, respectively. This good electrochemical performance is related to the fact that the elemental germanium nanoparticles present in the composite increases the reversibility of the conversion reaction of GeO2. These factors have been found through investigating and comparing GeO2/Ge/C, GeO2/C, nanosized GeO2, and bulk GeO2.
RESUMO
The aim of this study was to investigate the metabolic changes associated with the anti-obesity effects of fermented blackberry extracts in the liver tissues of high-fat-diet-fed mice using mass spectrometry-based metabolomics analysis. C57BL/6J mice were divided into eight groups: normal-diet-fed mice, high-fat-diet-fed mice, high-fat diet treated with blackberry extract, high-fat-diet mice treated with blackberry fermented by L. plantarum, and high-fat diet with blackberry fermented by L. brevis. After 12 weeks, the high-fat-diet group exhibited a greater increase in liver weight compared to the control group, and among the groups, the group administered with blackberry fermented with L. plantarum showed the most pronounced reduction in liver weight. As the primary organ responsible for amino acid metabolism, the liver is crucial for maintaining amino acid homeostasis. In our study, we observed that the levels of several essential amino acids, including isoleucine and valine, were decreased by the high-fat diet, and were recovered by administration of blackberry extract fermented with L. plantarum. Our results demonstrated the potential of blackberry extract fermented with L. plantarum as a functional material for metabolic disorders by restoring some of the amino acid metabolism disturbances induced by a high-fat diet.
RESUMO
The purpose of this work was to examine the effects of potassium poly-γ-glutamate (PGA-K) on mice fed a high-fat diet consisting of 60% of total calories for 12 weeks. PGA-K administration reduced the increase in body weight, epididymal fat, and liver weight caused by a high-fat diet compared to the obese group. The triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels, which are blood lipid indicators, were significantly increased in the obese group but were significantly decreased in the PGA-K-treated group. The administration of PGA-K resulted in a significant inhibition of pro-inflammatory cytokines, including tumor necrosis factor α and interleukin 6. Moreover, the levels of leptin and insulin, which are insulin resistance indicators, significantly increased in the obese group but were significantly decreased in the PGA-K-treated group. These results suggest that PGA-K exhibits a protective effect against obesity induced by a high-fat diet, underscoring its potential as a candidate for obesity treatment.
Assuntos
Bacillus subtilis , Dieta Hiperlipídica , Isoflavonas , Proteínas de Soja , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos Obesos , Obesidade/tratamento farmacológico , Obesidade/etiologia , Colesterol , Glutamatos , Camundongos Endogâmicos C57BLRESUMO
Upregulation of phospholipase D (PLD) is functionally linked with oncogenic signals and tumorigenesis. Caffeic acid phenethyl ester (CAPE) is an active compound of propolis extract that exhibits anti-proliferative, anti-inflammatory, anti-oxidant, and antineoplastic properties. In this study, we demonstrated that CAPE suppressed the expression of PLD1 at the transcriptional level via inhibition of binding of NFκB to PLD1 promoter. Moreover, CAPE, but not its analogs, bound to a Cys837 residue of PLD1 and inhibited enzymatic activity of PLD. CAPE also decreased activation of matrix metalloproteinases-2 induced by phosphatidic acid, a product of PLD activity. Ultimately, CAPE-induced downregulation of PLD1 suppressed invasion and proliferation of glioma cells. Taken together, the results of this study indicate that CAPE might contribute to anti-neoplastic effect by targeting PLD1.