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1.
Sci Total Environ ; 804: 149984, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34509834

RESUMO

Severe haze episodes occur frequently in the Seoul Metropolitan Area (SMA) and throughout East Asian countries, especially during the winter and early spring. We investigated the sources and chemistry of particulate matter (PM) during three winter haze episodes in Seoul that occurred between January 1st and February 10th in 2017 using a high resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) and positive matrix factorization (PMF) analysis. The average concentration of sub-micrometer aerosol (PM1 = NR-PM1 + black carbon (BC)) was 32.6 µg/m3, which was composed of 42% organics, 27% nitrate, 11% sulfate, 13% ammonium and 4% BC by mass. Six distinct sources of organic aerosol (OA) were identified: vehicle emitted hydrocarbon-like OA (HOA), cooking OA (COA), biomass burning OA (BBOA), and 3 different types of secondary OA (SOA) with varying degrees of oxidation and temporal trends. The nitrate mass fraction increased during the three haze episodes, with nitrate accounting for 27-33% of PM1 mass. Enhanced nitrate concentrations and higher nitrate oxidation ratios (NOR), despite lower enhancement in relative humidity (RH) than the low PM loading period, suggest that regional transport of nitrate contributed to the nitrate mass during the haze periods. Lower HOA and COA concentrations during the high PM loading periods further confirm that local emissions or stagnant meteorological conditions were not the main reason for the severe haze. Residence time analysis (RTA), concentration field analysis (CFA), and column-CFA results from FLEXPART also showed that the measurement period was accompanied by atmospheric transport of nitrate, sulfate, and ammonium from eastern China. Nevertheless, we found that NO2, a precursor of nitrate, was predominantly from local emissions. These findings suggest that nitrate in Seoul is not only locally formed, but also transported from upwind areas.


Assuntos
Poluentes Atmosféricos , Aerossóis/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Material Particulado/análise , Seul
2.
Environ Health ; 20(1): 110, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34670555

RESUMO

BACKGROUND: The differential effects of PM2.5 fractions on children's lung function remain inconclusive. This study aimed to examine whether lung function in asthmatic children was associated with increased PM2.5 fractions in urban areas in Nagasaki prefecture, Japan, where the air pollution level is relatively low but influenced by transboundary air pollution. METHODS: We conducted a multiyear panel study of 73 asthmatic children (boys, 60.3%; mean age, 8.2 years) spanning spring 2014-2016 in two cities. We collected self-measured peak expiratory flow (PEF) twice a day and daily time-series data for PM2.5 total mass and its chemical species. We fitted a linear mixed effects model to examine short-term associations between PEF and PM2.5, adjusting for individual and time-varying confounders. A generalized linear mixed effects model was also used to estimate the association for worsening asthma defined by severe PEF decline. Back-trajectory and cluster analyses were used to investigate the long-range transboundary PM2.5 in the study areas. RESULTS: We found that morning PEFs were adversely associated with higher levels of sulfate (- 1.61 L/min; 95% CI: - 3.07, - 0.15) in Nagasaki city and organic carbon (OC) (- 1.02 L/min; 95% CI: - 1.94, - 0.09) in Isahaya city, per interquartile range (IQR) increase at lag1. In addition, we observed consistent findings for worsening asthma, with higher odds of severe PEF decline in the morning for sulfate (odds ratio (OR) = 2.31; 95% CI: 1.12, 4.77) and ammonium (OR = 1.73; 95% CI: 1.06, 2.84) in Nagasaki city and OC (OR = 1.51; 95% CI: 1.06, 2.15) in Isahaya city, per IQR increase at lag1. The significant chemical species were higher on days that could be largely attributed to the path of Northeast China origin (for sulfate and ammonium) or both the same path and local sources (for OC) than by other clusters. CONCLUSIONS: This study provides evidence of the differential effects of PM2.5 fractions on lung function among asthmatic children in urban areas, where the Japanese national standards of air quality have been nearly met. Continuous efforts to promote mitigation actions and public awareness of hazardous transboundary air pollution are needed to protect susceptible children with asthma.

3.
Exp Mol Med ; 53(9): 1390-1401, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34552205

RESUMO

Obesity is now recognized as a disease. This study revealed a novel role for pyruvate dehydrogenase kinase (PDK) in diet-induced hypertrophic obesity. Mice with global or adipose tissue-specific PDK2 deficiency were protected against diet-induced obesity. The weight of adipose tissues and the size of adipocytes were reduced. Adipocyte-specific PDK2 deficiency slightly increased insulin sensitivity in HFD-fed mice. In studies with 3T3-L1 preadipocytes, PDK2 and PDK1 expression was strongly increased during adipogenesis. Evidence was found for epigenetic induction of both PDK1 and PDK2. Gain- and loss-of-function studies with 3T3-L1 cells revealed a critical role for PDK1/2 in adipocyte differentiation and lipid accumulation. PDK1/2 induction during differentiation was also accompanied by increased expression of hypoxia-inducible factor-1α (HIF1α) and enhanced lactate production, both of which were absent in the context of PDK1/2 deficiency. Exogenous lactate supplementation increased the stability of HIF1α and promoted adipogenesis. PDK1/2 overexpression-mediated adipogenesis was abolished by HIF1α inhibition, suggesting a role for the PDK-lactate-HIF1α axis during adipogenesis. In human adipose tissue, the expression of PDK1/2 was positively correlated with that of the adipogenic marker PPARγ and inversely correlated with obesity. Similarly, PDK1/2 expression in mouse adipose tissue was decreased by chronic high-fat diet feeding. We conclude that PDK1 and 2 are novel regulators of adipogenesis that play critical roles in obesity.

4.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073834

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease associated with obesity and insulin resistance. Activation of the purinergic receptor P2Y2R has been reported to promote adipogenesis, inflammation and dyslipidemia in adipose tissues in obese mice. However, the role of P2Y2R and its mechanisms in NAFLD remain unknown. We hypothesized that P2Y2R deficiency may play a protective role in NAFLD by modulating lipid metabolism in the liver. In this study, we fed wild type and P2Y2R knockout mice with a high-fat diet (HFD) for 12 weeks and analyzed metabolic phenotypes. First, P2Y2R deficiency effectively improved insulin resistance with a reduction in body weight and plasma insulin. Second, P2Y2R deficiency attenuated hepatic lipid accumulation and injury with reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Third, P2Y2R deficiency decreased the expression of fatty acid synthesis mediators (cluster of differentiation (CD36), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD1)); and increased the expression of adipose triglyceride lipase (ATGL), a lipolytic enzyme. Mechanistically, P2Y2R deficiency increased the AMP-activated protein kinase (AMPK) activity to improve mitochondrial fatty acid ß-oxidation (FAO) by regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1A (CPT1A)-mediated FAO pathway. In addition, P2Y2R deficiency increased peroxisome proliferator-activated gamma co-activator-1α (PGC-1α)-mediated mitochondrial biogenesis. Conclusively, P2Y2R deficiency ameliorated HFD-induced hepatic steatosis by enhancing FAO through AMPK signaling and PGC-1α pathway, suggesting P2Y2R as a promising therapeutic target for NAFLD.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Ácidos Graxos/metabolismo , Lipogênese/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Receptores Purinérgicos P2Y2/metabolismo , Acetil-CoA Carboxilase/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Peso Corporal , Antígenos CD36/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Dieta Hiperlipídica , Ácido Graxo Sintases/metabolismo , Insulina/sangue , Resistência à Insulina/fisiologia , Lipase/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/enzimologia , Obesidade/metabolismo , Receptores Purinérgicos P2Y2/deficiência , Receptores Purinérgicos P2Y2/genética , Estearoil-CoA Dessaturase/metabolismo
5.
Sci Total Environ ; 780: 146458, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34030340

RESUMO

Speciated hourly measurements of fine aerosols were made for more than two years at an urban, an industrial and a port site in Busan, Korea. A Generalized Additive Model (GAM) was designed to deconvolve factors contributing to the pollutant concentrations at multiple scales. The model yields estimates of source contributions to pollution by separately identifying the signals in the time series due to meteorology, vertical mixing, horizontal wind transport and temporal variations such as diurnal, weekly, seasonal and annual trends. The GAM model was expanded to include FLEXPART back trajectory clusters generated using fuzzy c-means clustering. This made it possible to quantify the impact of long-range transport using the Trajectory Cluster Contribution Function (TCCF). TCCF provides a development of methods such as Concentration Field Analysis and Potential Source Contribution Function by providing numerical estimates of concentration changes associated with different air mass transport patterns while accounting for possible confounding factors from meteorology. The GAM simulations identified the importance of local transport for primary pollutants and long-range transport from China for secondary pollutants. Local factors accounted for up to 72% of the variance in concentrations of NO2 and elemental carbon whereas large-scale/seasonal factors accounted for up to 56% of PM2.5 and 80% of inorganic species. The algorithm further identified the importance of the weekend effect and the holiday effect at the different sites in Busan. The residual from the analysis was used to estimate the impact of the COVID-19 pandemic. The signature of the pandemic was different between the pollutants as well as from site to site. The model was able to distinguish small impacts from local pollutants at the residential site; short-lived acute impacts from industrial changes; and longer-term changes due to the early pandemic response in China.

6.
J Biol Chem ; 296: 100469, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33639169

RESUMO

Alterations in mitochondrial fission may contribute to the pathophysiology of several neurodegenerative diseases, including Alzheimer's disease (AD). However, we understand very little about the normal functions of fission or how fission disruption may interact with AD-associated proteins to modulate pathogenesis. Here we show that loss of the central mitochondrial fission protein dynamin-related protein 1 (Drp1) in CA1 and other forebrain neurons markedly worsens the learning and memory of mice expressing mutant human amyloid precursor protein (hAPP) in neurons. In cultured neurons, Drp1KO and hAPP converge to produce mitochondrial Ca2+ (mitoCa2+) overload, despite decreasing mitochondria-associated ER membranes (MAMs) and cytosolic Ca2+. This mitoCa2+ overload occurs independently of ATP levels. These findings reveal a potential mechanism by which mitochondrial fission protects against hAPP-driven pathology.


Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Dinaminas/metabolismo , Dinâmica Mitocondrial/fisiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Precursor de Proteína beta-Amiloide/genética , Animais , Encéfalo/metabolismo , Região CA1 Hipocampal/metabolismo , Cálcio/metabolismo , Modelos Animais de Doenças , Dinaminas/genética , Dinaminas/fisiologia , Feminino , Hipocampo/metabolismo , Humanos , Aprendizagem/fisiologia , Masculino , Memória/fisiologia , Camundongos , Camundongos Transgênicos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/genética , Neurônios/metabolismo , Fosforilação
7.
Int J Mol Sci ; 22(4)2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33562139

RESUMO

Diabetic nephropathy (DN) is a common pathological feature in patients with diabetes and the leading cause of end-stage renal disease. Although several pharmacological agents have been developed, the management of DN remains challenging. Geniposide, a natural compound has been reported for anti-inflammatory and anti-diabetic effects; however, its role in DN remains poorly understood. This study investigated the protective effects of geniposide on DN and its underlying mechanisms. We used a C57BL/6 mouse model of DN in combination with a high-fat diet and streptozotocin after unilateral nephrectomy and treated with geniposide by oral gavage for 5 weeks. Geniposide effectively improves DN-induced renal structural and functional abnormalities by reducing albuminuria, podocyte loss, glomerular and tubular injury, renal inflammation and interstitial fibrosis. These changes induced by geniposide were associated with an increase of AMPK activity to enhance ULK1-mediated autophagy response and a decrease of AKT activity to block oxidative stress, inflammation and fibrosis in diabetic kidney. In addition, geniposide increased the activities of PKA and GSK3ß, possibly modulating AMPK and AKT pathways, efficiently improving renal dysfunction and ameliorating the progression of DN. Conclusively, geniposide enhances ULK1-mediated autophagy and reduces oxidative stress, inflammation and fibrosis, suggesting geniposide as a promising treatment for DN.


Assuntos
Anti-Inflamatórios/farmacologia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Autofagia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Iridoides/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Complicações do Diabetes/patologia , Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Fibrose/tratamento farmacológico , Fibrose/prevenção & controle , Glicogênio Sintase Quinase 3 beta/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos
8.
Am J Chin Med ; 49(1): 131-146, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33371811

RESUMO

Alcoholic liver damage is caused by ethanol and its oxidized intermediates, and endotoxin-induced acute liver failure is mediated by apoptosis and inflammation. We investigated whether extracts of sprouts of Panax ginseng (SG) attenuate alcohol or endotoxin-induced acute liver injury in mice. Whole SG contains eight times more ginsenosides than the root and, because it grows quickly ([Formula: see text]30 days) without using pesticides, the whole-plant can be harvested. The extracts were enriched in phenolics and flavonoids and showed high radical scavenging activities. Mice received oral administration of SG or fermented SG (FSG) extracts 1 h before an injection of either ethanol or lipopolysaccharide and D-galactosamine (LPS/GalN). The latency of righting reflex was monitored to examine the effect of extracts on relieving hangover symptoms. The results indicate that FSG significantly reduced the latency of righting reflex, SG and FSG increased the activity and expression of ethanol-metabolizing enzymes, and FSG decreased hepatic necrosis and plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). During the ethanol metabolism, cytochrome P450 2E1 expression was increased, but 4-hydroxynonenal levels were decreased by the extracts due to their anti-oxidant activity. LPS/GalN-induced liver injury was reduced by SG and FSG; plasma ALT and AST levels, hepatic necrosis, and apoptotic and inflammatory markers were all decreased. In conclusion, SG extracts attenuated ethanol-induced hangover and endotoxin-induced acute liver injury, and fermentation enhanced the efficacy with regard to relieving hangover.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Fermentação , Flavonoides/análise , Panax/química , Fenóis/análise , Fitoterapia , Plântula/química , Administração Oral , Animais , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Sequestradores de Radicais Livres , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR
9.
Nutrients ; 12(10)2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33080824

RESUMO

The rational regulation of programmed cell death by means of autophagy and apoptosis has been considered a potential treatment strategy for cancer. We demonstrated the inhibitory effect of St. John's Wort (SJW) on growth in the triple-negative breast cancer (TNBC) cell line and xenografted mice and its target mechanism concerning autophagic and apoptotic cell death. SJW ethanol extract (SJWE) inhibited proliferation in a dose-dependent manner. SJWE treatment dramatically increased autophagy flux and apoptosis compared with the control. The autophagy inhibitor, 3-methyladenine (3-MA), reversed the SJWE-induced inhibition of cell proliferation and regulation of autophagy and apoptosis, indicating that SJWE induced apoptosis through prodeath autophagy. Furthermore, SJWE inhibited tumor growth and induced autophagy and apoptosis in the tumor of MDA-MB-231 xenografted athymic nude mice. Our results indicate that SJWE might have great potential as a new anticancer therapy for triple-negative breast cancer by inducing prodeath autophagy and apoptosis.


Assuntos
Antineoplásicos Fitogênicos , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Hypericum/química , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Relação Dose-Resposta a Droga , Camundongos Nus , Transplante de Neoplasias , Extratos Vegetais/isolamento & purificação , Células Tumorais Cultivadas
10.
Biomedicines ; 8(9)2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32942603

RESUMO

Glutathione (GSH) is an endogenous antioxidant found in plants, animals, fungi, and some microorganisms that protects cells by neutralizing hydrogen peroxide. Honokiol, an active ingredient of Magnolia officinalis, is known for antioxidant, anti-inflammatory, and anti-bacterial properties. We investigated the protective mechanism of honokiol through regulating cellular GSH in renal proximal tubules against acute kidney injury (AKI). First, we measured cellular GSH levels and correlated them with the expression of GSH biosynthetic enzymes after honokiol treatment in human kidney-2 (HK-2) cells. Second, we used pharmacological inhibitors or siRNA-mediated gene silencing approach to determine the signaling pathway induced by honokiol. Third, the protective effect of honokiol via de novo GSH biosynthesis was investigated in renal ischemia-reperfusion (IR) mice. Honokiol significantly increased cellular GSH levels by upregulating the subunits of glutamate-cysteine ligase (Gcl)-Gclc and Gclm. These increases were mediated by activation of nuclear factor erythroid 2-related factor 2, via PI3K/Akt and protein kinase C signaling. Consistently, honokiol treatment reduced the plasma creatinine, tubular cell death, neutrophil infiltration and lipid peroxidation in IR mice and the effect was correlated with upregulation of Gclc and Gclm. Conclusively, honokiol may benefit to patients with AKI by increasing antioxidant GSH via transcriptional activation of the biosynthetic enzymes.

11.
Nutrients ; 12(9)2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32933130

RESUMO

Endotoxin-induced acute liver injury is mediated by an excessive inflammatory response, hepatocellular oxidative stress, and apoptosis. Traditional medicinal plants have been used to treat various disorders. Platycodon grandifloras (PG) has been shown to be beneficial in relieving cough and asthma and to have anti-tumor, anti-inflammatory, anti-diabetic activities. The pharmacological action of PG is mainly due to saponins, flavonoids, phenolic, and other compounds. However, raw PG exhibits some side effects at high doses. Here, we extracted raw PG with varying fermentation methods and examined its anti-inflammatory effect and associated signaling kinases in Raw264.7 cells. Then, we investigated the effect of fermented black PG (FBPG) on endotoxin-induced liver injury. Mice were administered FBPG orally at 1 h before the lipopolysaccharide and D-galactosamine (LPS/GalN) injection and sacrificed after 5 h. Black PG (BPG) and FBPG showed a significant reduction in pro-inflammatory cytokines and extracellular nitric oxide (NO); p-38 and ERK signaling was involved in reducing inducible NO synthase in Raw264.7 cells. Consistently, FBPG attenuates LPS/GalN-induced liver injury; plasma ALT and AST, hepatic necrosis, pro-inflammatory cytokines, apoptosis, and lipid peroxidation were all reduced. In conclusion, PG extracts, particularly FBPG, play anti-inflammatory, antioxidant, and anti-apoptotic roles, alleviating endotoxin-induced acute liver injury. Processing raw PG into FBPG extract may be clinically useful by improving the pharmacologically active ingredients and reducing the required dosage.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fígado/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico , Platycodon , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Citocinas/metabolismo , Endotoxinas , Fermentação , Galactosamina , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lipopolissacarídeos , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Necrose , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/farmacologia , Células RAW 264.7 , Transdução de Sinais
12.
Mol Metab ; 42: 101089, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32987187

RESUMO

OBJECTIVE: Diabetic nephropathy (DN) is one of the most common complications of diabetes and a critical risk factor for developing end-stage renal disease. Activation of purinergic receptors, including P2Y2R has been associated with the pathogenesis of renal diseases, such as polycystic kidney and glomerulonephritis. However, the role of P2Y2R and its precise mechanisms in DN remain unknown. We hypothesised that P2Y2R deficiency may play a protective role in DN by modulating the autophagy signalling pathway. METHODS: We used a mouse model of DN by combining a treatment of high-fat diet and streptozotocin after unilateral nephrectomy in wild-type or P2Y2R knockout mice. We measured renal functional parameter in plasma, examined renal histology, and analysed expression of autophagy regulatory proteins. RESULTS: Hyperglycaemia and ATP release were induced in wild type-DN mice and positively correlated with renal dysfunction. Conversely, P2Y2R knockout markedly attenuates albuminuria, podocyte loss, development of glomerulopathy, renal tubular injury, apoptosis and interstitial fibrosis induced by DN. These protective effects were associated with inhibition of AKT-mediated FOXO3a (forkhead box O3a) phosphorylation and induction of FOXO3a-induced autophagy gene transcription. Furthermore, inhibitory phosphorylation of ULK-1 was decreased, and the downstream Beclin-1 autophagy signalling was activated in P2Y2R deficiency. Increased SIRT-1 (sirtuin-1) and FOXO3a expression in P2Y2R deficiency also enhanced autophagy response, thereby ameliorating renal dysfunction in DN. CONCLUSIONS: P2Y2R contributes to the pathogenesis of DN by impairing autophagy and serves as a therapeutic target for treating DN.


Assuntos
Autofagia/fisiologia , Nefropatias Diabéticas/metabolismo , Receptores Purinérgicos P2Y2/metabolismo , Animais , Apoptose , Autofagia/genética , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Proteína Forkhead Box O3/metabolismo , Rim/metabolismo , Camundongos , Camundongos Knockout , Podócitos/patologia , Receptores Purinérgicos P2Y2/genética , Transdução de Sinais , Estreptozocina/farmacologia
13.
Nutrients ; 12(8)2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32781739

RESUMO

Non-alcoholic steatosis and insulin resistance are critical health problems and cause metabolic complications worldwide. In this study, we investigated the molecular mechanism of Polygonum multiflorum Thunb. (PM) against hepatic lipid accumulation and insulin resistance by using in vitro and in vivo models. PM extract significantly attenuated the accumulation of lipid droplets and hepatic triglyceride in free fatty acid (FFA)-exposed HepG2 cells. PM extract increased the AMPK and ACC phosphorylation and GLUT4 expression, whose levels were downregulated in FFA-exposed cells. PM extract also decreased precursor and mature forms of SREBP-1 in FFA-exposed cells. C57BL/6 mice fed with normal diet (ND) or high-fat diet (HFD) were administered PM extract (100 mg/kg) or vehicle orally for 16 weeks. PM extract attenuated the increases of the epididymal and perirenal fats on HFD feeding. PM extract markedly reduced hepatic lipid accumulation and fasting glucose levels, and improved glucose and insulin sensitivity in HFD-fed mice. HFD-fed mice decreased the AMPK and ACC phosphorylation and GLUT4 expression, and increased precursor and mature forms of SREBP-1; these changes were significantly restored by PM extract. In conclusion, PM extract alleviates non-alcoholic steatosis and insulin resistance through modulating the expression of proteins on lipid metabolism and glucose transport in the liver.


Assuntos
Fallopia multiflora , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/terapia , Extratos Vegetais/farmacologia , Raízes de Plantas , Acetil-CoA Carboxilase/metabolismo , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Fosforilação/efeitos dos fármacos , Proteínas Quinases/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
14.
Environ Sci Process Impacts ; 22(8): 1616-1653, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32672265

RESUMO

Anthropogenic emissions in Asia have significantly increased during the last two decades; as a result, the induced air pollution and its influences on radiative forcing and public health are becoming increasingly prominent. The Aerodyne Aerosol Mass Spectrometer (AMS) has been widely deployed in Asia for real-time characterization of aerosol chemistry. In this paper, we review the AMS measurements in Asia, mainly in China, Korea, Japan, and India since 2001 and summarize the key results and findings. The mass concentrations of non-refractory submicron aerosol species (NR-PM1) showed large spatial distributions with high mass loadings occurring in India and north and northwest China (60.2-81.3 µg m-3), whereas much lower values were observed in Korea, Japan, Singapore and regional background sites (7.5-15.1 µg m-3). Aerosol composition varied largely in different regions, but was overall dominated by organic aerosols (OA, 32-75%), especially in south and southeast Asia due to the impact of biomass burning. While sulfate and nitrate showed comparable contributions in urban and suburban regions in north China, sulfate dominated inorganic aerosols in south China, Japan and regional background sites. Positive matrix factorization analysis identified multiple OA factors from different sources and processes in different atmospheric environments, e.g., biomass burning OA in south and southeast Asia and agricultural seasons in China, cooking OA in urban areas, and coal combustion in north China. However, secondary OA (SOA) was a ubiquitous and dominant aerosol component in all regions, accounting for 43-78% of OA. The formation of different SOA subtypes associated with photochemical production or aqueous-phase/fog processing was widely investigated. The roles of primary emissions, secondary production, regional transport, and meteorology on severe haze episodes, and different chemical responses of primary and secondary aerosol species to source emission changes and meteorology were also demonstrated. Finally, future prospects of AMS studies on long-term and aircraft measurements, water-soluble OA, the link of OA volatility, oxidation levels, and phase state were discussed.


Assuntos
Poluentes Atmosféricos , Material Particulado , Aerossóis , Ásia , China , Monitoramento Ambiental , Índia , Japão , República da Coreia
15.
Nat Prod Res ; : 1-3, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32419489

RESUMO

To enhance the skin whitening effect, tyrosinase activity and melanin biosynthesis needs to be suppressed in the skin. To achieve this goal, we examined the extract of Thymus quinquecostatus flowers, and identified a functional ingredient, galuteolin. Galuteolin effectively inhibited melanin biosynthesis in B16/F10 cells, partially suppressing tyrosinase activity. Therefore, this study suggests that galuteolin can be used as a cosmetic ingredient for skin whitening.

16.
Food Sci Biotechnol ; 29(2): 275-281, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32064136

RESUMO

In this study, the protective effect of red pepper seed water extract (RPS) against the obesity in high fat diet (HFD)-fed mice was investigated (HFD control group, and HFD group treated with 100 or 200 mg/kg body weight of RPS for 13 weeks). The application of RPS partially reversed the HFD-induced increases in body weight and adipose tissue weight. The patterns of the adipose tissue weights were parallel to the patterns of fat area, as measured in DXA procedure. In the adipose tissue, RPS suppressed the expression of adipogenic transcription factors and adipose marker genes. AMP-activated protein kinase activation was observed in the adipose tissue by RPS treatment. In addition, RPS improved high homeostasis model assessment of insulin resistance and hyperlipidemia in HFD fed mice. These findings suggest that RPS can be used as a potential therapeutic substance for reducing body fat and obesity related diseases.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33409323

RESUMO

The Korea - United States Air Quality Study (May - June 2016) deployed instrumented aircraft and ground-based measurements to elucidate causes of poor air quality related to high ozone and aerosol concentrations in South Korea. This work synthesizes data pertaining to aerosols (specifically, particulate matter with aerodynamic diameters <2.5 micrometers, PM2.5) and conditions leading to violations of South Korean air quality standards (24-hr mean PM2.5 < 35 µg m-3). PM2.5 variability from AirKorea monitors across South Korea is evaluated. Detailed data from the Seoul vicinity are used to interpret factors that contribute to elevated PM2.5. The interplay between meteorology and surface aerosols, contrasting synoptic-scale behavior vs. local influences, is presented. Transboundary transport from upwind sources, vertical mixing and containment of aerosols, and local production of secondary aerosols are discussed. Two meteorological periods are probed for drivers of elevated PM2.5. Clear, dry conditions, with limited transport (Stagnant period), promoted photochemical production of secondary organic aerosol from locally emitted precursors. Cloudy humid conditions fostered rapid heterogeneous secondary inorganic aerosol production from local and transported emissions (Transport/Haze period), likely driven by a positive feedback mechanism where water uptake by aerosols increased gas-to-particle partitioning that increased water uptake. Further, clouds reduced solar insolation, suppressing mixing, exacerbating PM2.5 accumulation in a shallow boundary layer. The combination of factors contributing to enhanced PM2.5 is challenging to model, complicating quantification of contributions to PM2.5 from local versus upwind precursors and production. We recommend co-locating additional continuous measurements at a few AirKorea sites across South Korea to help resolve this and other outstanding questions: carbon monoxide/carbon dioxide (transboundary transport tracer), boundary layer height (surface PM2.5 mixing depth), and aerosol composition with aerosol liquid water (meteorologically-dependent secondary production). These data would aid future research to refine emissions targets to further improve South Korean PM2.5 air quality.

18.
J Clin Med ; 8(5)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31072024

RESUMO

Renal ischemia reperfusion (IR) is a main cause of acute kidney injury leading to high morbidity and mortality during postoperative periods. This study investigated whether ethyl pyruvate (EP) protects the kidney against renal IR injury. Male C57BL/6 mice were treated with vehicle or EP (40 mg/kg) 1 h before ischemia and the plasma creatinine (Cr) levels and tubular damage were evaluated after reperfusion. EP attenuated the IR-induced plasma Cr levels, renal inflammation and apoptotic cell death, but the effect of EP was abolished by pretreating Zinc protoporphyrin (ZnPP), a heme oxygenase (HO)-1 inhibitor. HO-1 is a stress-induced protein and protects the kidney against IR injury. EP increased significantly HO-1 expression in the proximal tubular cells in vivo and HK-2 cells in vitro. Inhibition of PI3K/Akt pathway and knockdown of Nrf2 blocked HO-1 induction by EP. High mobility group box 1 (HMGB1) secretion was assessed as an early mediator of IR injury; plasma HMGB1 were significantly elevated as early as 2 h to 24 h after reperfusion and these were attenuated by EP, but the effect of EP was abolished by ZnPP. EP also reduced HMGB1 secretion stimulated by TNF-α in HK-2 cells, and the inhibition of PI3K/Akt and knockdown of HO-1 blocked the effect of EP. Conclusively, EP inhibits the active secretion of HMGB1 from proximal tubular cells during IR injury by inducing HO-1 via activation of PI3K/Akt and Nrf2 pathway.

19.
Exp Mol Med ; 51(4): 1-16, 2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-31028246

RESUMO

Hepatic ischemia and reperfusion injury are characterized by impaired autophagy, mitochondrial dysfunction, and subsequent compromise of cellular homeostasis following hepatic surgery or transplantation. Nobiletin, a natural flavonoid, is a beneficial antioxidant that possesses anti-inflammatory and anti-cancer activities. We investigated the effect of nobiletin on hepatic IR injury and described the underlying mechanisms. C57BL/6 mice were subjected to 60 min of partial hepatic ischemia, treated with nobiletin (5 mg/kg) or vehicle at the start of reperfusion, and killed at 5 h of reperfusion. Hepatic ischemia and reperfusion increased hepatocellular oxidative damage, inflammation, and cell death, but these changes were alleviated upon nobiletin treatment. Nobiletin increased the expression of proteins that control autophagy, mitochondrial dynamics, and biogenesis. Specifically, the SIRT-1/FOXO3a and PGC-1α pathways were activated by nobiletin. IR-induced AKT activation was associated with FOXO3a phosphorylation, which resulted in a significant reduction in the nuclear FOXO3a levels and potentially attenuated autophagy-regulatory gene expression. Nobiletin increased FOXO3a expression and its nuclear translocation via the inhibition of AKT. Specific inhibition of SIRT-1 abolished the protective effect of nobiletin, causing decreased FOXO3a expression, followed by autophagy induction and decreased PGC-1α expression and mitochondrial dynamics. Taken together, our data indicate that SIRT-1 directly mediates the protective effect of nobiletin against hepatic ischemia and reperfusion injury. The activation of autophagy and mitochondrial function through the SIRT-1/FOXO3a and PGC-1α pathways indicate that nobiletin could have therapeutic potential for treating hepatic ischemia and reperfusion injury.


Assuntos
Autofagia/efeitos dos fármacos , Flavonas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Proteína Forkhead Box O3 , Hepatopatias/genética , Hepatopatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Biogênese de Organelas , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Sirtuína 1/genética , Sirtuína 1/metabolismo
20.
Chemosphere ; 225: 713-722, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30903845

RESUMO

New particle formation and growth events (NPEs) were frequently observed (17 out of 60 days) during April 14 to June 15, 2016 in the Seoul metropolitan area (SMA). In this study, we investigated the chemical mechanisms of new particle growth based on measurements conducted using an aerodyne high resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) and a scanning mobility particle sizer (SMPS). Both instruments were deployed as a part of the KORUS-AQ campaign (Korea-US Air Quality study). NPEs usually started around noon time between ∼11:00 and 14:00 with the appearance of an ultrafine mode peaking between ∼20 and 30 nm (in mobility diameter, Dm, measured by the SMPS operating in the range 18-947 nm) followed by the growth of this modal diameter to 50-100 nm during the next ∼6-18 h. The growth rate of NPEs during the study was on average 4.48 ±â€¯1.39 nm/h. Comparing to the non-NPE days in SMA, NPEs occurred under the conditions of lower concentration of preexisting particles, higher ozone (48 vs 30 ppb), stronger solar radiation (2.53 vs1.20 MJ/m2), and drier air (34 vs 65%). The HR-ToF-AMS size-resolved aerosol composition measurements show that LV-OOA (low volatility oxidized organic aerosol) and sulfate were major contributors to the growth of new particles at the initial stage of NPE which mostly occurred during daytime and that the later growth which extended into nighttime was mainly contributed by semi-volatile condensable species such as nitrate and SV-OOA (semi-volatile oxygenated organic aerosol). Generally new particles grew to a modal size of ∼80 nm (12 out of 17 NPEs) over the course of an event, however, particles could grow to larger than 100 nm when nitrate concentration was high whereas particle growth was limited to ∼ 50 nm when nitrate, SV-OOA or sulfate were low.


Assuntos
Poluentes Atmosféricos/química , Monitoramento Ambiental/métodos , Tamanho da Partícula , Material Particulado/química , Poluentes Atmosféricos/análise , Material Particulado/análise , República da Coreia , Seul
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