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Int J Mol Sci ; 20(18)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31540416


We investigated whether magnesium sulfate (MgSO4) mitigated pulmonary hypertension progression in rats. Pulmonary hypertension was induced by a single intraperitoneal injection of monocrotaline (60 mg/kg). MgSO4 (100 mg/kg) was intraperitoneally administered daily for 3 weeks, from the seventh day after monocrotaline injection. Adult male rats were randomized into monocrotaline (MCT) or monocrotaline plus MgSO4 (MM) groups (n = 15 per group); control groups were maintained simultaneously. For analysis, surviving rats were euthanized on the 28th day after receiving monocrotaline. The survival rate was higher in the MM group than in the MCT group (100% versus 73.3%, p = 0.043). Levels of pulmonary artery wall thickening, α-smooth muscle actin upregulation, right ventricular systolic pressure increase, and right ventricular hypertrophy were lower in the MM group than in the MCT group (all p < 0.05). Levels of lipid peroxidation, mitochondrial injury, inflammasomes and cytokine upregulation, and apoptosis in the lungs and right ventricle were lower in the MM group than in the MCT group (all p < 0.05). Notably, the mitigation effects of MgSO4 on pulmonary artery wall thickening and right ventricular hypertrophy were counteracted by exogenous calcium chloride. In conclusion, MgSO4 mitigates pulmonary hypertension progression, possibly by antagonizing calcium.

Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Sulfato de Magnésio/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Progressão da Doença , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/patologia , Masculino , Monocrotalina , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Ratos , Ratos Sprague-Dawley
High Alt Med Biol ; 20(3): 293-302, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31329475


Background: This study aimed to explore the effects of netrin-1 on hypobaric hypoxia-induced lung injury in mice. Methods: We exposed 6-8-week-old C57BL/6 mice to hypobaric stress at 340 mmHg for 30 minutes followed by 260 mmHg for different periods (6, 12, 18, and 24 hours) to observe the severity of lung injury (O2 concentration, 21%; 54.6 mmHg). The wet/dry weight ratio and protein leakage from the mouse lung were used to determine the suitable exposure time. Netrin-1 was injected into the tail vein of mice before 18-hour decompression. Inflammatory cytokines, lung injury scores, and activity of nuclear factor κB were evaluated. The expression of apoptosis-related proteins was also examined. Results: Protein concentration in the bronchoalveolar lavage fluid was significantly higher in the 18-hour group (p < 0.05). Pulmonary pathology revealed neutrophil infiltration, alveolar septum thickening, and tissue edema. Injury score and macrophage inflammatory protein 2 levels were also increased. Intrinsic apoptosis pathway was activated. Hypoxia decreased the expression of Bcl2 protein, the number of active caspase-3-stained cells, and UNC5HB receptors. Pretreatment with netrin-1 reduced protein leakage, inhibited neutrophil migration, lowered the injury score, attenuated apoptosis, and increased UNC5HB receptor expression. Conclusion: Netrin-1 dampens hypobaric hypoxia-induced lung injury by inhibiting neutrophil migration and attenuating apoptosis.

BMC Cancer ; 18(1): 379, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29614990


BACKGROUND: Temozolomide (TMZ)-induced side effects and drug tolerance to human gliomas are still challenging issues now. Our previous studies showed that honokiol, a major bioactive constituent of Magnolia officinalis (Houpo), is safe for normal brain cells and can kill human glioma cells. This study was further aimed to evaluate the improved effects of honokiol and TMZ on drug-sensitive and -resistant glioma cells and the possible mechanisms. METHODS: TMZ-sensitive human U87-MG and murine GL261 glioma cells and TMZ-resistant human U87-MR-R9 glioma cells were exposed to honokiol and TMZ, and cell viability and LC50 of honokiol were assayed. To determine the death mechanisms, caspase-3 activity, DNA fragmentation, apoptotic cells, necrotic cells, cell cycle, and autophagic cells. The glioma cells were pretreated with 3-methyladenine (3-MA) and chloroquine (CLQ), two inhibitors of autophagy, and then exposed to honokiol or TMZ. RESULTS: Exposure of human U87-MG glioma cells to honokiol caused cell death and significantly enhanced TMZ-induced insults. As to the mechanism, combined treatment of human U87-MG cells with honokiol and TMZ induced greater caspase-3 activation, DNA fragmentation, cell apoptosis, and cell-cycle arrest at the G1 phase but did not affect cell necrosis. The improved effects of honokiol on TMZ-induced cell insults were further verified in mouse GL261 glioma cells. Moreover, exposure of drug-tolerant human U87-MG-R9 cells to honokiol induced autophagy and consequent apoptosis. Pretreatments with 3-MA and CLQ caused significant attenuations in honokiol- and TMZ-induced cell autophagy and apoptosis in human TMZ-sensitive and -tolerant glioma cells. CONCLUSIONS: Taken together, this study demonstrated the improved effects of honokiol with TMZ on autophagy and subsequent apoptosis of drug-sensitive and -tolerant glioma cells. Thus, honokiol has the potential to be a drug candidate for treating human gliomas.

Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Compostos de Bifenilo/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Lignanas/farmacologia , Temozolomida/farmacologia , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Glioma , Humanos
Nutr Res ; 52: 87-97, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29525610


Arctigenin (ATG), a lignin extracted from Arctium lappa (L.), exerts antioxidant and anti-inflammatory effects. We hypothesized that ATG exerts a protective effect on hepatocytes by preventing nonalcoholic fatty liver disease (NAFLD) progression associated with lipid oxidation-associated lipotoxicity and inflammation. We established an in vitro NAFLD cell model by using normal WRL68 hepatocytes to investigate oleic acid (OA) accumulation and the potential bioactive role of ATG. The results revealed that ATG inhibited OA-induced lipid accumulation, lipid peroxidation, and inflammation in WRL68 hepatocytes, as determined using Oil Red O staining, thiobarbituric acid reactive substance assay, and inflammation antibody array assays. Quantitative RT-PCR analysis demonstrated that ATG significantly mitigated the expression of acetylcoenzyme A carboxylase 1 and sterol regulatory element-binding protein-1 and significantly increased the expression of carnitine palmitoyltransferase 1 and peroxisome proliferator-activated receptor alpha. The 40 targets of the Human Inflammation Antibody Array indicated that ATG significantly inhibited the elevation of the U937 lymphocyte chemoattractant, ICAM-1, IL-1ß, IL-6, IL-6sR, IL-7, and IL-8. ATG could activate the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and AMP-activated protein kinase (AMPK) pathways and could increase the phosphorylation levels of Akt and AMPK to mediate cell survival, lipid metabolism, oxidation stress, and inflammation. Thus, we demonstrated that ATG could inhibit NAFLD progression associated with lipid oxidation-associated lipotoxicity and inflammation, and we provided insights into the underlying mechanisms and revealed potential targets to enable a thorough understanding of NAFLD progression.

Arctium/química , Furanos/farmacologia , Lignanas/farmacologia , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Fosfatidilinositol 3-Quinase/metabolismo , Extratos Vegetais/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Fígado Gorduroso/metabolismo , Fígado Gorduroso/prevenção & controle , Furanos/uso terapêutico , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/prevenção & controle , Molécula 1 de Adesão Intercelular/metabolismo , Interleucinas/metabolismo , Lignanas/uso terapêutico , Fígado/citologia , Fígado/metabolismo , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácido Oleico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PPAR alfa/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fitoterapia , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
Biomed Res Int ; 2017: 8284363, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29226150


Purpose of Review: Transversus abdominis plane (TAP) block is a regional technique for analgesia of the anterolateral abdominal wall. This review highlights the nomenclature system and recent advances in TAP block techniques and proposes directions for future research. Recent Findings: Ultrasound guidance is now considered the gold standard in TAP blocks. It is easy to acquire ultrasound images; it can be used in many surgeries involving the anterolateral abdominal wall. However, the efficacy of ultrasound-guided TAP blocks is not consistent, which might be due to the use of different approaches. The choice of technique influences the involved area and block duration. To investigate the actual analgesic effects of TAP blocks, we unified the nomenclature system and clarified the definition of each technique. Although a single-shot TAP block is limited in duration, it is still the candidate of the analgesic standard for abdominal wall surgery because the use of the catheter technique and liposomal bupivacaine may overcome this limitation. Summary: Ultrasound-guided TAP blocks are commonly used. With the unified nomenclature and the development of catheter technique and/or liposomal local anesthetics, TAP blocks can be applied more appropriately to achieve better pain control.

Músculos Abdominais/efeitos dos fármacos , Bloqueio Nervoso/métodos , Parede Abdominal , Analgesia/métodos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/química , Bupivacaína/administração & dosagem , Bupivacaína/química , Humanos , Lipossomos/administração & dosagem , Lipossomos/química , Manejo da Dor/métodos , Ultrassonografia de Intervenção/métodos
Shock ; 32(2): 164-71, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19008781


UNLABELLED: To test the hypothesis that dexamethasone (Dex) treatment would restore rat hepatic bile acid coenzyme A-amino acid N-acyltransferase (rBAT) expression in septic rats after cecal ligation and puncture by increasing expression of retinoic acid X receptor alpha (RXRalpha), we assessed survival rate and bile and bile salt concentration in the Dex-treated septic group and compared these results with those for a nontreated septic group, a Dex-treated nonseptic group, and a sham group. Dexamethasone treatment (0.01 mg/kg) significantly improved the survival rate and increased the bile and bile salt concentration in the bile ducts of septic rats (P = <0.05). In our assessment of bile salt-related genes, during sepsis, there were decreases in protein and mRNA expression of rBAT and cholesterol 7 alpha-hydroxylase (CYP7A1). Treatment with Dex restored expression of rBAT and RXR[alpha] but not CYP7A1, bile salt export pump, or multidrug resistance associated protein 2 (MRP2). Na+-taurocholate cotransport protein and organic anion transporting polypeptide 1 were unchanged. In addition, treatment with Dex also restored the DNA-binding activity of RXR/farnesoid-X receptor to rBAT promoter containing inverted repeat 1 sequence. In an experiment to confirm our findings, RXR[alpha] siRNA was found to significantly block Dex-induced increases in expression of rBAT in hepatocytes taken from septic rats (P < 0.01). CONCLUSION: Dex restored the expression of rBAT in septic rats by enhancing RXR[alpha], a process that might explain the mechanism underlying Dex's anticholestatic effect.

Aciltransferases/biossíntese , Anti-Inflamatórios/farmacologia , Dexametasona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Receptor X Retinoide alfa/metabolismo , Sepse/metabolismo , Transportadores de Cassetes de Ligação de ATP/biossíntese , Animais , Bile/metabolismo , Ductos Biliares/metabolismo , Colesterol 7-alfa-Hidroxilase/biossíntese , Masculino , Transportadores de Ânions Orgânicos Dependentes de Sódio/biossíntese , Transportadores de Ânions Orgânicos Sódio-Independentes/biossíntese , RNA Interferente Pequeno/farmacologia , Ratos , Ratos Sprague-Dawley , Elementos de Resposta , Simportadores/biossíntese