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1.
An Acad Bras Cienc ; 91(3): e20180646, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31411259

RESUMO

The hepatoprotective effects of the ethanolic extracts of propolis (EEP) on alcohol-induced liver steatosis were investigated in Wistar rats. Chronic alcoholic fatty liver was induced by administration of 52% alcohol to male Wistar rats at the dose of 1% body weight for 7 weeks. Then animals were simultaneously treated with 50% ethanol solutions of EEP or normal saline at the dose of 0.1% body weight for 4 further weeks. Serological analyses and liver histopathology studies were performed to investigate the development of steatosis. Microarray analysis was conducted to investigate the alterations of hepatic gene expression profiling. Our results showed that 4-week treatment of EEP helped to restore the levels of various blood indices, liver function enzymes and the histopathology of liver tissue to normal levels. Results from the microarray analysis revealed that the hepatic expressions of genes involved in lipogenesis were significantly down-regulated by EEP treatment, while the transcriptional expressions of functional genes participating in fatty acids oxidation were markedly increased. The ability of EEP to reduce the negative effects of alcohol on liver makes propolis a potential natural product for the alternative treatment of alcoholic fatty liver.


Assuntos
Fígado Gorduroso Alcoólico/metabolismo , Hepatopatias Alcoólicas/metabolismo , Extratos Vegetais/metabolismo , Própole/metabolismo , Substâncias Protetoras/metabolismo , Alanina Transaminase/metabolismo , Animais , Apiterapia/métodos , Aspartato Aminotransferases/metabolismo , Colesterol/metabolismo , Modelos Animais de Doenças , Etanol , Ácidos Graxos/biossíntese , Fígado Gorduroso Alcoólico/tratamento farmacológico , Fígado Gorduroso Alcoólico/genética , Fígado Gorduroso Alcoólico/patologia , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/patologia , Masculino , Oxirredução , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Própole/química , Própole/uso terapêutico , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Ratos Wistar , Análise Serial de Tecidos/métodos , Transcrição Genética/genética , Triglicerídeos/metabolismo
2.
Chem Biol Interact ; 309: 108714, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31228470

RESUMO

Acetylcholinesterase (AChE) is an enzyme which terminates the cholinergic neurotransmission, by hydrolyzing acetylcholine at the nerve and nerve-muscle junctions. The reversible inhibition of AChE was suggested as the pre-treatment option of the intoxications caused by nerve agents. Based on our derived 3D-QSAR model for the reversible AChE inhibitors, we designed and synthesized three novel compounds 8-10, joining the tacrine and aroylacrylic acid phenylamide moieties, with a longer methylene chain to target two distinct, toplogically separated anionic areas on the AChE. The targeted compounds exerted low nanomolar to subnanomolar potency toward the E. eel and human AChE's as well as the human BChE and showed mixed inhibition type in kinetic studies. All compounds were able to slow down the irreversible inhibition of the human AChE by several nerve agents including tabun, soman and VX, with the estimated protective indices around 5, indicating a valuable level of protection. Putative noncovalent interactions of the selected ligand 10 with AChE active site gorge were finally explored by molecular dynamics simulation suggesting a formation of the salt bridge between the protonated linker amino group and the negatively charged Asp74 carboxylate side chain as a significant player for the successful molecular recognition in line with the design strategy. The designed compounds may represent a new class of promising leads for the development of more effective pre-treatment options.


Assuntos
Substâncias para a Guerra Química/química , Inibidores da Colinesterase/química , Colinesterases/metabolismo , Substâncias Protetoras/química , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Sítios de Ligação , Domínio Catalítico , Substâncias para a Guerra Química/metabolismo , Inibidores da Colinesterase/metabolismo , Colinesterases/química , Humanos , Cinética , Simulação de Dinâmica Molecular , Compostos Organofosforados/química , Compostos Organofosforados/metabolismo , Substâncias Protetoras/metabolismo , Relação Quantitativa Estrutura-Atividade , Soman/química , Soman/metabolismo
3.
Food Chem Toxicol ; 131: 110582, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31220535

RESUMO

Alcoholism is a serious addiction that can lead to various health complications such as liver fibrosis, steatosis, and cirrhosis. Carvacrol is present in many plant-based essential oils and used as a preservative in the food industry. In this study, we have investigated the hepatoprotective role of carvacrol against ethanol-induced liver toxicity in mice. To determine the effect of carvacrol on liver injury parameters, 5 doses of 50% ethanol (10 mL/kg body weight) were orally administered every 12 h for inducing the hepatotoxicity in experimental mice. Interestingly, carvacrol pre-treatment (50 and 100 mg/kg) reversed the ethanol-induced effects on liver function, antioxidant markers, matrix metalloproteinases activities, and histological changes. Moreover, carvacrol binds to the active pocket of cytochrome P450 (Cyt P450) and inhibits its expression. Thus, our finding suggests carvacrol can be used as an adjuvant for the amelioration of alcohol-induced hepatotoxicity.


Assuntos
Inibidores das Enzimas do Citocromo P-450/uso terapêutico , Fígado Gorduroso Alcoólico/prevenção & controle , Monoterpenos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Animais , Autofagia/efeitos dos fármacos , Bebedeira , Domínio Catalítico , Inibidores das Enzimas do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/metabolismo , Fígado Gorduroso Alcoólico/patologia , Fígado/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Metaloproteinases da Matriz/metabolismo , Camundongos Endogâmicos ICR , Simulação de Acoplamento Molecular , Monoterpenos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/metabolismo , Ligação Proteica
4.
Mol Med Rep ; 19(6): 4852-4862, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059068

RESUMO

Cerebrovascular disease (CVD) is one of the leading causes of mortality worldwide. The role of cytochrome c oxidase subunit 6B1 (COX6B1) in the central nervous system remains unclear. The present study aimed to analyze the role of COX6B1 in rat hippocampal neurons extracted from fetal rats. The subcellular localization of the neuron­specific marker microtubule­associated protein 2 was detected by immunofluorescence assay. Cell viability was assessed using a cell counting kit, and the levels of apoptosis and cytosolic Ca2+ were analyzed by flow cytometry. The expression levels of the molecular factors downstream to COX6B1 were determined using reverse transcription­quantitative polymerase chain reaction and western blotting. Reoxygenation following oxygen­glucose deprivation (OGD) decreased cell viability and the expression levels of COX6B1 in a time­dependent manner, and 60 min of reoxygenation was identified as the optimal time period for establishing an ischemia/reperfusion (I/R) model. Overexpression of COX6B1 was demonstrated to reverse the viability of hippocampal neurons following I/R treatment. Specifically, COX6B1 overexpression decreased the cytosolic concentration of Ca2+ and suppressed neuronal apoptosis, which were increased following I/R treatment. Furthermore, overexpression of COX6B1 increased the protein expression levels of apoptosis regulator BCL­2 and mitochondrial cytochrome c (cyt c), and decreased the protein expression levels of apoptosis regulator BCL2­associated X and cytosolic cyt c in I/R model cells. Collectively, the present study results suggested that COX6B1 overexpression may reverse I/R­induced neuronal damage by increasing the viability of neurons, by decreasing the cytosolic levels of Ca2+ and by suppressing apoptosis. These results may facilitate the development of novel strategies for the prevention and treatment of CVD.


Assuntos
Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/farmacologia , Neurônios/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Lobo Temporal/metabolismo , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transtornos Cerebrovasculares/prevenção & controle , Citocromos c/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Feminino , Glucose/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/patologia , Oxigênio/metabolismo , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Lobo Temporal/patologia , Proteína bcl-X/metabolismo
5.
Cell Mol Biol (Noisy-le-grand) ; 65(4): 63-68, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31078154

RESUMO

To investigate the expressions and roles of semaphorin3A (Sema3A) and vascular endothelial growth factor 165 (VEGF165) in cultured rat cortical neurons and vascular endothelial cells after oxygen glucose deprivation (OGD) stimulation. Cultured cortical neurons (NC) and vascular endothelial cells (VEC) of Sprague Dawley (SD) rats (SPF grade) were randomly divided into control group and OGD treatment group. Western blot assay, immunofluorescent staining and immunohistochemical methods were used to determine the expressions of VEGF165, Sema3A and neuropilin-1 (Nrp-1) protein. Cell migration was determined by Transwell, while TUNEL assay was used to measure apoptosis. The expressions of Sema3A, Nrp-1 and VEGF165 in NC and VEC cells after OGD treatment were up-regulated, when compared with the control group. With transfection of Sema3A shRNA, apoptosis of neurons decreased significantly after 2 h of OGD treatment, but the apoptosis of VEC cells was not obvious. The migration rate of VEC cells in the treatment group was significantly increased, relative to that of the control group. Stimulation with OGD induces neuronal expression of VEGF165 and regulates the migration of vascular endothelial cells, thereby enhancing their participation in angiogenesis, which may involve Sema3A.


Assuntos
Córtex Cerebral/patologia , Células Endoteliais/metabolismo , Glucose/deficiência , Neurônios/metabolismo , Oxigênio/metabolismo , Semaforina-3A/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Apoptose , Movimento Celular , Forma Celular , Células Cultivadas , Células Endoteliais/patologia , Neurônios/patologia , Neuropilina-1/metabolismo , Substâncias Protetoras/metabolismo , Ratos Sprague-Dawley
6.
Mol Immunol ; 112: 1-9, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31078114

RESUMO

UFL1 was identified as a key regulator of cellular stress, which was found to possess anti-inflammatory and cytoprotection effect in LPS-stimulated bovine mammary epithelial cells in our previous study. The NLRP3 inflammasome, which responds to various pathogenic microorganisms and sterile stressors, is involved in multiple inflammatory diseases. However, the specific effects of UFL1 on NLRP3 inflammasome activation remain elusive. Here we investigated the role of UFL1, with a focus on NLRP3 inflammasome activation and the regulation of pyroptosis in LPS-stimulated BMECs. In this study, we observed an elevating NLRP3, Caspase-1 activation and IL-1ß secretion in mammary tissue of cows with mastitis and LPS-stimulated BMECs, and the experimental results here demonstrated that UFL1 depletion aggravated the LPS-induced NLRP3, Caspase-1 and IL-1ß expression. Overexpression of UFL1 significantly suppressed the expression of NLRP3, Caspase-1 and IL-1ß in BMECs. In addition, the suppression of NLRP3 inflammasome activation by UFL1 was partly mediated through the regulation of NF-κB signaling and ROS production. Furthermore, UFL1 overexpression could alleviate NLRP3 inflammasome activation-mediated pyroptosis in LPS-stimulated BMECs. These findings indicate that UFL1 can moudulate NLRP3 inflammasome activation and serve as effective strategies to diminish cell damage in inflammatory response by targeting NLRP3 inflammasome activation.


Assuntos
Células Epiteliais/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Substâncias Protetoras/metabolismo , Piroptose/fisiologia , Ubiquitina-Proteína Ligases/metabolismo , Animais , Caspase 1/metabolismo , Bovinos , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Piroptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
7.
J Agric Food Chem ; 67(25): 6978-6994, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31070363

RESUMO

Ripened Pu-erh tea extract contributes to reducing weight gain and fat accumulation; however, the role of gut microbiota on the antiobesity effect of ripened Pu-erh tea extract in obese mice remains unclear. This study aims to explore the role of alterations in gut microbes mediated by ripened Pu-erh tea extract in obese mice through 16S rRNA sequencing and a fecal transplant trial. Our results suggested that drinking water containing ripened Pu-erh tea extract could decrease weight gain, fat accumulation, adipose inflammation, the Firmicutes-to-Bacteroidetes ratio, and metabolic endotoxemia while, in the meantime, improving the intestinal barrier integrity in obese mice. Moreover, the fecal transplant trial indicated that feces from the donor mice treated with ripened Pu-erh tea extract could significantly modulate weight and metabolic syndrome in the recipient mice. Thus, our results indicated that gut microbiota can mediate the function of ripened Pu-erh tea extract against obesity; additionally, ripened Pu-erh tea extract can potentially prevent individuals from being obese through rebalancing the gut microbiota.


Assuntos
Microbioma Gastrointestinal , Obesidade/dietoterapia , Extratos Vegetais/metabolismo , Substâncias Protetoras/metabolismo , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , DNA Bacteriano/genética , Humanos , Intestinos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/microbiologia , RNA Ribossômico 16S/genética , Chá/metabolismo
8.
Mol Biol Rep ; 46(3): 3101-3112, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30977085

RESUMO

Chronic overuse of common pharmaceuticals, e.g. acetaminophen (paracetamol), often leads to the development of acute liver failure (ALF). This study aimed to elucidate the effect of cultured mesenchymal stem cells (MSCs) proteome on the onset of liver damage and regeneration dynamics in animals with ALF induced by acetaminophen, to test the liver protective efficacy of MSCs proteome depending on the oxygen tension in cell culture, and to blueprint protein components responsible for the effect. Protein compositions prepared from MSCs cultured in mild hypoxic (5% and 10% O2) and normal (21% O2) conditions were used to treat ALF induced in mice by injection of acetaminophen. To test the effect of reduced oxygen tension in cell culture on resulting MSCs proteome content we applied a combination of high performance liquid chromatography and mass-spectrometry (LC-MS/MS) for the identification of proteins in lysates of MSCs cultured at different O2 levels. The treatment of acetaminophen-administered animals with proteins released from cultured MSCs resulted in the inhibition of inflammatory reactions in damaged liver; the area of hepatocyte necrosis being reduced in the first 24 h. Compositions obtained from MSCs cultured at lower O2 level were shown to be more potent than a composition prepared from normoxic cells. A comparative characterization of protein pattern and identification of individual components done by a cytokine assay and proteomics analysis of protein compositions revealed that even moderate hypoxia produces discrete changes in the expression of various subsets of proteins responsible for intracellular respiration and cell signaling. The application of proteins prepared from MSCs grown in vitro at reduced oxygen tension significantly accelerates healing process in damaged liver tissue. The proteomics data obtained for different preparations offer new information about the potential candidates in the MSCs protein repertoire sensitive to oxygen tension in culture medium, which can be involved in the generalized mechanisms the cells use to respond to acute liver failure.


Assuntos
Acetaminofen/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/terapia , Meios de Cultivo Condicionados/metabolismo , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/terapia , Células-Tronco Mesenquimais/metabolismo , Proteoma , Animais , Biomarcadores , Biópsia , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Meios de Cultivo Condicionados/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Hipóxia/metabolismo , Falência Hepática Aguda/patologia , Masculino , Espectrometria de Massas , Células-Tronco Mesenquimais/citologia , Camundongos , Consumo de Oxigênio , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Proteômica/métodos
9.
Food Chem ; 290: 246-254, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31000044

RESUMO

Whether caseinate oligochitosan-glycation of the transglutaminase-type followed by trypsin digestion could lead to better protection against the acrylamide-induced cell barrier damage was investigated. Compared with caseinate digest, glycated caseinate digest had similar amount of Lys and Arg but lower -NH2 (0.557 versus 0.508 mol/kg protein) and total amide (1.12 versus 1.05 mol/kg protein) contents, and contained glucosamine at 5.74 g/kg protein. Acrylamide damaged barrier function of IEC-6 cells efficiently, leading to increased paracellular permeability and lactate dehydrogenase release, decreased trans-epithelial electrical resistance, and destroyed tight junction. The two digests alleviated these barrier dysfunctions via reversing index values. Three cellular proteins (ZO-1, occludin, and claudin-1) crucial to tight junction were up-regulated by the two digests. Furthermore, glycated caseinate digest was always more effective than caseinate digest to improve cell barrier function. This oligochitosan glycation is thus desired, as it ensures glycated protein digest with higher potential to protect intestinal barrier function.


Assuntos
Acrilamida/química , Caseínas/metabolismo , Quitina/análogos & derivados , Acrilamida/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quitina/química , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Glicosilação , Humanos , Mucosa Intestinal/citologia , Ocludina/genética , Ocludina/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Peptídeos/farmacologia , Permeabilidade/efeitos dos fármacos , Substâncias Protetoras/química , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo
10.
Oxid Med Cell Longev ; 2019: 3021785, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30911344

RESUMO

Cardiovascular disease (CVD) events are the main causes of death in end-stage renal disease (ESRD) patients on dialysis. The number and severity of CVD events remain inappropriate and difficult to explain by considering only the classic CVD risk factors. Our aim was to clarify the changes and the relationship of lipoprotein subfractions with other CVD risk factors, namely, body mass index (BMI) and adipokines, inflammation and low-density lipoprotein (LDL) oxidation, and the burden of the most prevalent comorbidities, diabetes mellitus (DM) and hypertension (HT). We studied 194 ESRD patients on dialysis and 22 controls; lipid profile, including lipoprotein subpopulations and oxidized LDL (oxLDL), C-reactive protein (CRP), adiponectin, leptin, and paraoxonase 1 activity were evaluated. Compared to controls, patients presented significantly lower levels of cholesterol, high-density lipoprotein cholesterol (HDLc), LDLc, oxLDL, and intermediate and small HDL and higher triglycerides, CRP, adiponectin, large HDL, very-low-density lipoprotein (VLDL), and intermediate-density lipoprotein- (IDL) B. Adiponectin levels correlated positively with large HDL and negatively with intermediate and small HDL, oxLDL/LDLc, and BMI; patients with DM (n = 17) and with DM+HT (n = 70), as compared to patients without DM or HT (n = 69) or only with HT (n = 38), presented significantly higher oxLDL, oxLDL/LDLc, and leptin and lower adiponectin. Obese patients (n = 45), as compared to normoponderal patients (n = 81), showed lower HDLc, adiponectin, and large HDL and significantly higher leptin, VLDL, and intermediate and small HDL. In ESRD, the higher adiponectin seems to favor atheroprotective HDL modifications and protect LDL particles from oxidative atherogenic changes. However, in diabetic and obese patients, adiponectin presents the lowest values, oxLDL/LDLc present the highest ones, and the HDL profile is the more atherogenic. Our data suggest that the coexistence of DM and adiposity in ESRD patients on dialysis contributes to a higher CVD risk, as showed by their lipid and adipokine profiles.


Assuntos
Adiponectina/metabolismo , Índice de Massa Corporal , Diabetes Mellitus/patologia , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Lipoproteínas/metabolismo , Substâncias Protetoras/metabolismo , Arildialquilfosfatase/metabolismo , Proteína C-Reativa/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Environ Sci Pollut Res Int ; 26(12): 12247-12263, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30835071

RESUMO

Oxidative stress plays a significant role in the pathophysiology of numerous kidney diseases, generally mediated by reactive oxygen species (ROS). Arsenic (Ar) is known to exert its toxicity through the generation of ROS and inflammation. The current study investigates the protective effects of sulforaphane (SFN) against arsenic-induced renal damage via PI3K/Akt-mediated Nrf2 pathway signaling. Thirty-two male albino Wistar rats were randomly divided into four groups of eight animals each, designated as control, arsenic (Ar), sulforaphane plus Ar (SFN+Ar), and sulforaphane alone (SFN), with oral administration of Ar (5 mg/kg BW) and SFN (80 mg/kg BW) daily for 28 days. Ar administration significantly (P < 0.05) increased the levels of ROS, OHdG, Ar accumulation, and lipid peroxidation, and decreased levels of enzymatic and nonenzymatic antioxidants. Notably, a significant (P < 0.05) increase was observed in markers of apoptosis, DNA damage, TUNEL-positive cells, and dark staining of ICAM-1 in renal tissue with decreased PI3K/Akt/Nrf2 gene expression. The biochemical findings were supported by histopathological and electron microscopy evaluation, which showed severe renal damage in rats treated with Ar. Pretreatment with SFN significantly (P < 0.05) attenuated renal ROS, OHdG, lipid peroxidation, and DNA damage, and increased phase II antioxidants via PI3K/Akt-mediated Nrf2 activation in renal tissue. These results show that dietary supplementation with SFN protects against Ar-induced nephrotoxicity via the PI3K/Akt-mediated Nrf2 signaling pathway in the rat kidney.


Assuntos
Arsênico/toxicidade , Substâncias Perigosas/toxicidade , Isotiocianatos/metabolismo , Substâncias Protetoras/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Rim/fisiologia , Peroxidação de Lipídeos , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/fisiologia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
12.
Food Chem ; 288: 422-443, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30902313

RESUMO

Maca (Lepidium meyenii Walpers) has emerged as a popular functional plant food due to various claimed health effects. This review details the major (i.e., starch, dietary fiber, and protein) and minor constituents (i.e., minerals, non-starch polysaccharides, polyphenols (flavonolignans), macaenes, macamides, glucosinolates, and alkaloids) of maca (root and aerial parts). Diverse health effects of maca are also summarized. Various bioactivities of maca include enhanced reproductive health, antifatigue, antioxidation, neuroprotection, antimicrobial activity, anticancer, hepatoprotection, immunomodulation, and improving skin health and digestive system's function. Plant genetics, botanical parts, processing, extraction, and experimental protocols represent the major factors affecting the chemical composition, physicochemical attributes, and health effects of maca-based products. However, clinical studies to support the claimed health effects of maca and related mechanisms appear to be lacking. Product innovation and diversification in food and non-food utilization of different parts of maca to maximize the value perceptions are suggested.


Assuntos
Lepidium/química , Extratos Vegetais/química , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Humanos , Lepidium/metabolismo , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Proteínas de Plantas/metabolismo , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Substâncias Protetoras/química , Substâncias Protetoras/metabolismo , Reprodução/efeitos dos fármacos
13.
Food Funct ; 10(4): 2114-2124, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30919867

RESUMO

The aim of this study was to investigate the potential protective effect of virgin coconut oil (VCO) on oxidative stress parameters in the liver, kidneys and heart of alloxan-induced (150 mg kg-1 i.p.-1) diabetes in rats. Our results showed that daily supplementation of VCO (20% of food) for 16 weeks significantly (p < 0.05) ameliorates some deleterious effects caused by alloxan. VCO reduced the diabetes-related increase in food (82.15 ± 1.49 vs. 145.51 ± 4.81 g per kg b.m. per day) and water (305.49 ± 6.09 vs. 583.98 ± 14.80 mL per kg b.m. per day) intake, and the decrease in the body mass gain (0.56 ± 0.16 vs. -2.13 ± 0.49 g per 100 g b.m. per week). In all three tissues, diabetes caused an increase in the concentration of total glutathione and sulfhydryl groups, and catalase and glutathione S-transferase activities, without changes in superoxide dismutase activity. Glutathione peroxidase activity was increased in the kidneys and heart, but not in the liver of the diabetic animals, while glutathione reductase activity was increased in the liver and the kidneys, and not in the heart. The simultaneous VCO supplementation increased the concentration of the sulfhydryl group in all three tissues of diabetic animals and decreased the glutathione S-transferase activity and glutathione concentration, without affecting the glutathione reductase activity. In the liver of diabetic animals it decreased superoxide dismutase, catalase and glutathione peroxidase activities, in the heart catalase and glutathione peroxidase activities, and in the kidney catalase activity only. The results of canonical discriminant analysis of oxidative stress parameters revealed that VCO exerts its effects in a tissue-specific manner.


Assuntos
Óleo de Coco/metabolismo , Diabetes Mellitus Experimental/dietoterapia , Rim/metabolismo , Fígado/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo , Substâncias Protetoras/metabolismo , Aloxano/efeitos adversos , Animais , Catalase/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Masculino , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
14.
J Pediatr Surg ; 54(6): 1168-1173, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30879750

RESUMO

INTRODUCTION: Umbilical mesenchymal stem cells (USC) have been shown to reduce illness in animal models of necrotizing enterocolitis (NEC), possibly through the paracrine release of hydrogen sulfide (H2S). We hypothesized that animals treated with USCs with inhibited H2S synthesis would exhibit more severe disease. METHODS: NEC was induced in five-day-old mouse pups by formula feeding and hypoxic and hypothermic stress. Experimental groups received intraperitoneal injection of either saline vehicle or 80,000cells/gram of one of the following cell types: USC, USCs with negative-control siRNA, or USCs with targeted siRNA inhibition of the H2S-producing enzymes. Pups were monitored by clinical assessment and after euthanasia, intestine and lung histologic injury were scored. Tissue was homogenized, and concentrations of IL-6, IL-10, and VEGF were determined by ELISA. For statistical analysis, p<0.05 was considered significant. RESULTS: Animals treated with negative-control siRNA USCs were significantly improved compared to vehicle. Clinical sickness scores as well as intestinal and lung histologic injury scores in the targeted siRNA groups were significantly worse when compared to the negative-control siRNA group. IL-6, IL-10, and VEGF had varying patterns of expression in the different groups. CONCLUSION: Inhibition of H2S production in USCs reduces the beneficial effects of these cells during therapy in experimental NEC. LEVEL OF EVIDENCE: Animal studies are typically described as "foundational evidence" without a true level assigned. TYPE OF STUDY: Animal Study.


Assuntos
Enterocolite Necrosante , Sulfeto de Hidrogênio , Células-Tronco Mesenquimais , Substâncias Protetoras , Cordão Umbilical/citologia , Animais , Modelos Animais de Doenças , Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/fisiopatologia , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Camundongos , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia
15.
Int J Mol Med ; 43(5): 2086-2102, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30864680

RESUMO

The purpose of the present study was to investigate whether bone marrow mesenchymal stem cells (BMMSCs) modified by CXC­chemokine receptor type 3 (CXCR3) and heme oxygenase­1 (HO­1) genes can repair damaged intestinal epithelial cells in vitro, and the role of the p38 mitogen­activated protein kinase (p38­MAPK) pathway in this process. A model of intestinal epithelial crypt cell line­6 (IEC­6) damage was created, and BMMSCs were transfected with either the CXCR3 and/or HO­1 gene in vitro. There were nine experimental groups in which the damaged IEC­6 cells were co­cultured with differentially­treated BMMSCs and lymphocytes for 24 h. Reverse transcription­quantitative polymerase chain reaction analysis, immunohistochemistry and a western blot analysis were performed to detect stem cell transfection, the repair of damaged intestinal epithelial cells and the expression of related molecules in the P38­MAPK pathway, respectively. Crystal violet staining and live cell imaging were used to detect the chemotaxis of BMMSCs. Flow cytometry was used to detect T lymphocyte activity and the surface markers expressed on BMMSCs. An ELISA was used to quantify cytokine production. The adenovirus (Ad)­CXCR3/MSCs exhibited the characteristics of stem cells and exhibited chemotaxis. The Ad­CXCR3/MSCs and Ad­(CXCR3 + HO)/MSCs exhibited increased expression of tight junction protein zonula occludens­1 (ZO­1) and anti­proliferating cell nuclear antigen in the damaged IEC­6 cells, and apoptosis of the damaged IEC­6 cells was decreased. BMMSCs inhibited the phosphorylation of p38, in addition to downstream molecules of the p38MAPK signaling pathway. The Ad­CXCR3/MSCs and Ad­(CXCR3 + HO)/MSCs exhibited significantly decreased expression levels of downstream molecules, including phosphorylated (p)­p38, p­activated transcription factor 2, p­C/EBP homologous protein­10, and p­myocyte enhancer factor 2C, and target molecules (e.g., apoptotic bodies). The effects of Ad­(CXCR3 + HO)/MSCs on the repair of the damaged intestinal tract and inhibition of the p38­MAPK pathway was more marked than those in other groups on day 7 post­surgery in the rejection model for small bowel transplantation. BMMSCs modified by the CXCR3 and HO­1 genes exhibited superior ability to repair damaged intestinal epithelial cells and served this role via the p38­MAPK pathway.


Assuntos
Enterócitos/metabolismo , Enterócitos/patologia , Heme Oxigenase-1/genética , Sistema de Sinalização das MAP Quinases , Células-Tronco Mesenquimais/metabolismo , Substâncias Protetoras/metabolismo , Receptores CXCR3/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Apoptose , Linhagem Celular , Sobrevivência Celular , Quimiotaxia , Heme Oxigenase-1/metabolismo , Intestino Delgado/transplante , Linfócitos/metabolismo , Masculino , Transplante de Células-Tronco Mesenquimais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Reprodutibilidade dos Testes , Proteínas de Junções Íntimas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
16.
Int J Mol Med ; 43(5): 2033-2043, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30864731

RESUMO

Sirtuin 1 (Sirt1) exerts its cardioprotective effects in various cardiovascular diseases via multiple cellular activities. However, the therapeutic implications of Sirt1 in hypoxic cardiomyocytes and the underlying mechanisms remain elusive. The present study investigated whether Sirt1 regulates autophagy and apoptosis in hypoxic H9C2 cardiomyocytes and in an experimental hypoxic mouse model. Right ventricular outflow tract biopsies were obtained from patients with cyanotic or acyanotic congenital heart diseases. Adenovirus Ad­Sirt1 was used to activate Sirt1 and Ad­Sh­Sirt1 was used to inhibit Sirt1 expression in H9C2 cells, in order to investigate the effect of Sirt1 on cellular autophagy and apoptosis. SRT1720, a pharmacological activator of Sirt1 and EX­527, a Sirt1 antagonist, were administered to mice to explore the role of Sirt1 in hypoxic cardiomyocytes in vivo. The levels of autophagy and apoptosis­related proteins were evaluated using western blotting. Apoptosis was investigated by TUNEL staining and Annexin V/7­aminoactinomycin D flow cytometry analysis. Heart tissue samples from cyanotic patients exhibited increased autophagy and apoptosis, as well as elevated Sirt1 levels, compared with the noncyanotic control samples. The data from the western blot analysis revealed that Sirt1 promoted autophagic flux and reduced apoptosis in hypoxic H9C2 cells. In addition, Sirt1 activated AMP­activated protein kinase (AMPK), and the AMPK inhibitor Compound C abolished the effect of Sirt1 on autophagy activation. Further exploration of the mechanism revealed that Sirt1 protects hypoxic cardiomyocytes from apoptosis, at least in part, through inositol requiring kinase enzyme 1α (IRE1α). Consistent with the in vitro results, treatment with the Sirt1 activator SRT1720 activated AMPK, inhibited IRE1α, enhanced autophagy, and decreased apoptosis in the heart tissues of normoxic mice compared with the hypoxia control group. Opposite changes were observed in hypoxic mice treated with the Sirt1 inhibitor EX­527. These results suggested that Sirt1 promoted autophagy via AMPK activation and reduced hypoxia­induced apoptosis via the IRE1α pathway, to protect cardiomyocytes from hypoxic stress.


Assuntos
Apoptose , Autofagia , Miócitos Cardíacos/metabolismo , Substâncias Protetoras/metabolismo , Sirtuína 1/metabolismo , Estresse Fisiológico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Carbazóis/farmacologia , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular , Cianose/patologia , Modelos Animais de Doenças , Endorribonucleases/metabolismo , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Lactente , Masculino , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
17.
Med Sci Monit ; 25: 928-936, 2019 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-30710072

RESUMO

BACKGROUND Endothelial injury is the early pathological change of cerebral aneurysm (CA) formation. In addition to its lipid-lowering activity, atorvastatin (ATR) also reportedly promotes vascular repair via mobilizing endothelial progenitor cells (EPC). Here, we investigated the influence of ATR on vascular worsening after CA induction in rats. MATERIAL AND METHODS Adult male Sprague-Dawley rats were randomly assigned to 3 groups: a control (CTR) group, a CA group, and a CA+ATR treatment group. Circulating EPC level and hematological and lipid profiles were measured 3 months after CA induction. Verhoeff-Van Gieson staining and transmission electron microscopy were performed to assess pathological changes in the artery wall. RT-PCR was also performed to evaluate the expression of inflammation-related genes in the aneurysmal wall. RESULTS ATR significantly restored the impaired level of circulating EPC without changing hematological and lipid profiles 3 months after CA induction. ATR markedly inhibited endothelial injury, media thinning, and CA enlargement, accompanied by reduced vascular inflammation. CONCLUSIONS Our preliminary results demonstrate that the mobilization of EPC and improvement of endothelial function by ATR contribute to the prevention of cerebral aneurysm. Further studies are warranted to investigate the detailed mechanism.


Assuntos
Atorvastatina/metabolismo , Aneurisma Intracraniano/patologia , Animais , Atorvastatina/farmacologia , Movimento Celular , Modelos Animais de Doenças , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/patologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Aneurisma Intracraniano/tratamento farmacológico , Aneurisma Intracraniano/prevenção & controle , Masculino , Substâncias Protetoras/metabolismo , Ratos , Ratos Sprague-Dawley
18.
Life Sci ; 221: 187-195, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30716336

RESUMO

AIMS: The interplay between bone marrow stromal cells (BMSCs) and acute myeloid leukemia (AML) cells plays a critical role in AML drug resistance by secreting growth factors, cytokines, and extracellular vesicles. As kind of extracellular vesicles, exosomes consist of proteins and RNAs and regulate communication among cells. MAIN METHODS: The BMSCs, HS5 cells, and AML cells were co-cultivated with transwell membranes, and treated with different doses of AML chemotherapy drug, etoposide. KEY FINDINGS: Findings of our research proved that co-cultivation of BMSCs with AML cells defended AML against cell death triggered via etoposide, without having an impact on cell growth. An increase in the expression of the 70 kDa heat shock proteins (HSP70) as well as lysosomal associated membrane protein 3 (CD63) was observed in the exosomes from BMSC and AML, co-cultivated in conditioned media. Exosome repression in BMSC and AML co-cultivating system rebuilt the sensitivity of the KG1A cells to apoptosis triggered via etoposide, indicating that exosome modulated drug resistance in AML. Our study proved that exosomes arising from KG1A cells could propel BMSCs to generate IL-8, which could regulate the effect of etoposide treatment. Furthermore, IL-8 inhibition by its antibody increased the sensitivity of AML cells to cell death triggered via etoposide. SIGNIFICANCE: Our results suggested that exosomes secreted by AML cells is an essential communicator for the interaction of BMSCs and AML, which can protect AML cells from chemotherapy drug induced apoptosis.


Assuntos
Exossomos/fisiologia , Leucemia Mieloide Aguda/metabolismo , Células-Tronco Mesenquimais/metabolismo , Adulto , Apoptose , Proliferação de Células , Técnicas de Cocultura , Resistencia a Medicamentos Antineoplásicos/fisiologia , Etoposídeo/farmacologia , Exossomos/metabolismo , Feminino , Humanos , Interleucina-8/metabolismo , Masculino , Células-Tronco Mesenquimais/fisiologia , Cultura Primária de Células , Substâncias Protetoras/metabolismo , Células Tumorais Cultivadas
19.
Int J Mol Sci ; 20(4)2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30781642

RESUMO

As the use of nanoparticles (NPs) is increasing, the potential toxicity and behavior of NPs in living systems need to be better understood. Our goal was to evaluate the developmental toxicity and bio-distribution of two different sizes of fluorescently-labeled SiO2 NPs, 25 and 115 nm, with neutral surface charge or with different surface functionalization, rendering them positively or negatively charged, in order to predict the effect of NPs in humans. We performed a zebrafish embryo toxicity test (ZFET) by exposing the embryos to SiO2 NPs starting from six hours post fertilization (hpf). Survival rate, hatching time, and gross morphological changes were assessed at 12, 24, 36, 48, 60, and 72 hpf. We evaluated the effect of NPs on angiogenesis by counting the number of sub-intestinal vessels between the second and seventh intersegmental vessels and gene expression analysis of vascular endothelial growth factor (VEGF) and VEGF receptors at 72 hpf. SiO2 NPs did not show any adverse effects on survival rate, hatching time, gross morphology, or physiological angiogenesis. We found that SiO2 NPs were trapped by the chorion up until to the hatching stage. After chemical removal of the chorion (dechorionation), positively surface-charged SiO2 NPs (25 nm) significantly reduced the survival rate of the fish compared to the control group. These results indicate that zebrafish chorion acts as a physical barrier against SiO2 NPs, and removing the chorions in ZFET might be necessary for evaluation of toxicity of NPs.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Nanopartículas/toxicidade , Dióxido de Silício/toxicidade , Testes de Toxicidade , Peixe-Zebra/embriologia , Animais , Córion/metabolismo , Embrião não Mamífero/anatomia & histologia , Embrião não Mamífero/irrigação sanguínea , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Substâncias Protetoras/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Análise de Sobrevida , Suspensões , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Ecotoxicol Environ Saf ; 173: 314-321, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30784794

RESUMO

Excessive chromium (Cr) causes toxicity to plants, while the beneficial effects of selenium (Se) have been verified in plants under various adverse conditions. Under Cr stress, the impacts of exogenous Se on root morphology and metal element uptake were investigated in root of Chinese cabbage by cellular and biochemical approaches. Exogenous Se alleviated Cr-induced irreversible damage to root morphology, plasma membrane integrity and ultrastructure of root tip cells. Compared with Cr treatment alone, exogenous Se reduced root Cr content by 17%. Se supply changed the subcellular distribution of Cr in root, and the concentration of Cr was reduced in the fractions of plastids and mitochondria, while increased in soluble fraction. Besides, exogenous Se counteracted the nutrient elements (Na, Ca, Fe, Mn, Cu and Zn) loss induced by Cr. For plant with Se pretreatment, the increase rate of Cr influx was lower than that of plant without Se pretreatment, particularly in solution containing high concentration (100-400 µmol L-1) of Cr. In addition, higher Km value was observed in plant with Se pretreatment, which indicated a lower Cr affinity than that of plant without Se pretreatment. The results suggest that Se modified root morphology and regulated nutrient elements uptake by root, which might play a combined role in reducing Cr uptake by root, consequently alleviating Cr stress and maintaining plant growth.


Assuntos
Brassica/efeitos dos fármacos , Cromo/efeitos adversos , Raízes de Plantas/efeitos dos fármacos , Selênio/metabolismo , Poluentes do Solo/efeitos adversos , Transporte Biológico , Brassica/anatomia & histologia , Brassica/metabolismo , Raízes de Plantas/anatomia & histologia , Raízes de Plantas/metabolismo , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/metabolismo , Selênio/administração & dosagem
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