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1.
J Int Med Res ; 50(8): 3000605221115388, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35915871

RESUMO

OBJECTIVE: To determine if the beneficial effects of transient desflurane application mitigates inflammation and decrease associated signaling induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) in mice. METHODS: Mice were induced to develop Parkinson's disease (PD) by intraperitoneal injection with MPTP for 20 consecutive days, and validated mice were randomly allocated to four groups. Collected samples from euthanized mice were designated for the following analyses: 1) immunohistochemical staining for positive dopaminergic neurons in the substantia nigra and striatum, 2) immunofluorescence staining for ionized calcium binding adaptor molecule-1 (Iba1) and glial fibrillary acid protein (GFAP), and 3) western blotting for p38, p-p38, toll-like receptor 4, and tumor necrosis factor (TNF)-α. RESULTS: The inhalation of desflurane for 1 hour ameliorated locomotory dysfunctions of PD mice by recovering the loss of Iba1- and GFAP-positive dopaminergic neurons, deactivating microglial cells and astrocytes, and decreasing the amounts of inflammatory cytokines (TNF-α). CONCLUSIONS: These findings suggest that transient desflurane inhalation may provide some benefits for PD through ameliorating inflammation and enhancing locomotor activity.


Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Doença de Parkinson , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/metabolismo , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Desflurano , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Substância Negra/metabolismo , Substância Negra/patologia
3.
Am J Chin Med ; 49(8): 1913-1927, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34775933

RESUMO

Myocardial ischemia/reperfusion injury (MIRI) is the major cause of myocardial cell damage in acute myocardial infarction, and its treatment remains a clinical challenge. Ginsenoside Rb1 showed protective effects on the cardiovascular system; however, the underlying mechanism remains largely unclear. Effects of Ginsenoside Rb1 on rat MIRI-induced myocardial infarct size were evaluated through TTC staining. TUNEL assay and flow cytometry analysis were employed to estimate cell apoptosis. Apoptosis, autophagy and PI3K/Akt/mTOR pathway-related proteins were estimated via western blot. Expression of Beclin1 in myocardial tissues were examined by immunohistochemical analysis. Expression levels of IL-1[Formula: see text], TNF-[Formula: see text] and IL-6 were tested by enzyme-linked immunosorbent assay (ELISA). Here, we found that Ginsenoside Rb1 treatment not only alleviated MIRI in rats but also protected H9C2 cells against hypoxia/reoxygenation induced damage. Ginsenoside Rb1 abolished the MIRI-induced activation of autophagy. Meanwhile, we found that treatment of 3-MA (autophagy inhibitor) could enhance the protective effects of Ginsenoside Rb1 on H9C2 cells during H/R. Moreover, Ginsenoside Rb1 treatment resulted in the activation of the PI3K/Akt/mTOR pathway, and treatment of LY294002 (PI3K/Akt pathway repressor) abolished the protective effects of Ginsenoside Rb1 on myocardial in vitro and in vivo. Our results suggest that Ginsenoside Rb1 functions as a protector against MIRI by repressing cardiomyocyte autophagy through the PI3K/Akt/mTOR signaling pathway.


Assuntos
Traumatismo por Reperfusão Miocárdica , Animais , Apoptose , Autofagia , Ginsenosídeos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-33936245

RESUMO

OBJECTIVE: To perform a systematic evaluation of the efficacy and safety of combined treatment of Shenmai injection and chemotherapy for lung cancer. METHODS: A literature search for randomized controlled trials (RCTs) describing the treatment of lung cancer by Shenmai injection and chemotherapy or chemotherapy alone was performed using the PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Value In Paper (VIP), China BioMed, and Wanfang databases. The databases were searched for entries published before September 1, 2019. RESULTS: Thirty-seven RCTs, comprising a total of 2808 cases, were included in the present meta-analysis. Of these, 1428 cases were treated by Shenmai injection plus chemotherapy, and 1380 cases were treated only by chemotherapy. The results of meta-analysis showed that the combined treatment (Shenmai injection plus chemotherapy) increased the short-term efficacy of treatment (relative risk [RR] = 1.183, 95% confidence interval [CI] = 1.043-1.343, P < 0.01) and improved patients' quality of life (RR = 1.514, 95%CI = 1.211-1.891, P < 0.01) compared with chemotherapy alone. With regard to the adverse effects, the combined treatment markedly reduced the incidence of white blood cell (WBC) reduction (RR = 0.846, 95%CI = 0.760-0.941, P < 0.01), platelet reduction (RR = 0.462, 95% CI = 0.330-0.649, P < 0.01), and hemoglobin reduction (RR = 0.462, 95% CI = 0.330-0.649, P < 0.01) and alleviated drug-induced liver injury (RR = 0.677, 95%CI = 0.463-0.990, P < 0.05). However, it did not offer a significant protective effect (RR = 0.725, 95%CI = 0.358-1.468, P < 0.05). The effect of the combined treatment on the occurrence of vomiting was considerable (RR = 0.889, 95%CI = 0.794-0.996, P < 0.05), and the combined treatment markedly increased the immunity of patients with lung cancer. CONCLUSION: The combined treatment of Shenmai injection plus chemotherapy enhanced the short-term efficacy of chemotherapy, improved the patient quality of life, alleviated the adverse effects of chemotherapeutics, and increased the patient immunity. These results should be confirmed by large-scale, high-quality RCTs.

5.
Lab Invest ; 101(7): 865-877, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33758383

RESUMO

Myocardial ischemia/reperfusion injury (MIRI) causes severe damage in cardiac tissue, thereby resulting in a high rate of mortality. 6-Gingerol (6-G) is reported to play an essential role in alleviating MIRI. However, the underlying mechanism remains obscure. This study was intended to explore the potential mechanism by which 6-G functions. Q-PCR was employed to quantify the relative RNA levels of long noncoding RNA (lncRNA) H19 (H19), miR-143, and ATG7, an enzyme essential for autophagy, in HL-1 cells. Western blotting, immunofluorescence, and immunohistochemistry were employed for protein evaluation in cultured cells or mouse tissues. Cell viability, cytotoxicity, and apoptosis were analysed by CCK-8, LDH, and flow cytometry assays, respectively. The binding sites for miR-143 were predicted using starBase software and experimentally validated through a dual-luciferase reporter system. Here, we found that 6-G elevated cellular H19 expression in hypoxia/reoxygenation (H/R)-treated HL-1 cells. Moreover, 6-G increased Bcl-2 expression but reduced cleaved caspase 3 and caspase 9 protein levels. Mechanistically, H19 directly interacted with miR-143 and lowered its cellular abundance by acting as a molecular sponge. Importantly, ATG7 was validated as a regulated gene of miR-143, and the depletion of miR-143 by H19 caused an increased in ATG7 expression, which in turn promoted the autophagy process. Last, mouse experiments highly supported our in vitro findings that 6-G relieves MIRI by enhancing autophagy. The H19/miR-143/ATG7 axis was shown to be critical for the function of 6-G in relieving MIRI.


Assuntos
Autofagia/efeitos dos fármacos , Catecóis/farmacologia , Álcoois Graxos/farmacologia , Traumatismo por Reperfusão Miocárdica/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Proteína 7 Relacionada à Autofagia/metabolismo , Linhagem Celular , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Transdução de Sinais/efeitos dos fármacos
6.
Chemosphere ; 267: 129205, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33338709

RESUMO

Soil plays a fundamental role in food safety and the adverse effects of contaminants like heavy metal (loid)s on crop quality have threatened human health. Therefore, it is important to focus on the food safety and agricultural soil pollution by heavy metals, especially for China where the demand for food production is increasing. This review comprehensively introduced the current status of agricultural soil pollution by heavy metals in China, analyzed the main sources of contaminants, including the applications of pesticides and fertilizers, atmospheric deposition related to vehicle emissions and coal combustion, sewage irrigation and mining. Food safety and agricultural soil pollution by heavy metals, the removal technologies for soil remediation such as soil amendments, phytoremediation and foliar sprays were also introduced. The review can provide significant insights for policymakers, environmental engineers, and agro-technicians regarding soil contamination control and management strategies and technologies.


Assuntos
Metais Pesados , Poluentes do Solo , China , Monitoramento Ambiental , Poluição Ambiental , Inocuidade dos Alimentos , Humanos , Metais Pesados/análise , Solo , Poluentes do Solo/análise , Tecnologia
7.
J Mol Neurosci ; 71(3): 515-526, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32901371

RESUMO

The effective prevention of postoperative cognitive dysfunction (POCD) needs to be explored, and the effect of preoperative pain on POCD remains unclear. We established a chronic pain model induced by chronic constriction injury (CCI) and models of acute pain and anxiety without pain in mice that were subsequently subjected to partial hepatectomy surgery. Morris water maze (MWM) tests were performed to evaluate the learning and memory abilities of the mice. ELISA was used to measure IL-1ß, IL-6, and TNF-α in serum, and HPLC-MS was used to detect neurotransmitters in the prefrontal cortices and hippocampi of the mice. The results indicated that chronic pain induced by CCI might have significantly impaired the learning and memory abilities of mice, while acute pain and anxiety without pain only affected the memory abilities of mice. Perioperative acute pain increased the level of IL-1ß in serum, and CCI might have increased the level of IL-6. CCI and acute pain increased dopamine (DA) levels in the cortex, similar to anxiety. Like anxiety, CCI increased 5-hydroxytryptamine (5-HT) levels in the prefrontal cortex and hippocampus. Acute pain led to a decrease in the acetylcholine (ACH) level in the hippocampus. Our results suggest that acute pain and CCI-induced chronic pain might aggravate postoperative cognitive dysfunction via neurotransmitters and by changing the levels of inflammatory factors such as IL-1ß and IL-6.


Assuntos
Acetilcolina/metabolismo , Dor Aguda/metabolismo , Dor Crônica/metabolismo , Dopamina/metabolismo , Complicações Cognitivas Pós-Operatórias/metabolismo , Serotonina/metabolismo , Dor Aguda/fisiopatologia , Animais , Dor Crônica/fisiopatologia , Hepatectomia/efeitos adversos , Hipocampo/metabolismo , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Complicações Cognitivas Pós-Operatórias/fisiopatologia , Córtex Pré-Frontal/metabolismo , Fator de Necrose Tumoral alfa/sangue
8.
Pain Med ; 22(1): 15-21, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33040141

RESUMO

BACKGROUND: Studies have provided some evidence that pain is a risk factor for postoperative delirium (POD). Therefore, we investigated the relationship between preoperative pain and POD after noncardiac surgery. METHODS: POD was assessed with the Montreal Cognitive Assessment, and preoperative cognition was assessed with the Mini-Mental State Examination. Plasma C-reactive protein (CRP) was detected by enzyme-linked immunosorbent assay before surgery. Preoperative pain was classified by its duration before surgery as chronic pain (lasting more than 1 month), acute pain (lasting less than 1 month), or no pain (no obvious pain). Multiple linear regression was used to adjust for confounding. RESULTS: From October 15, 2018, through August 12, 2019, a total of 67 patients were randomized; 7 were excluded because they were discharged before the seventh postoperative day. The prevalence of POD was significantly higher in the acute pain group (13 of 20; 65%) than in the chronic pain group (5 of 20; 25%) or the no pain group (6 of 20; 30%) (P = 0.019), indicating that delirium is associated with preoperative acute pain. The plasma level of preoperative CRP was also higher in the acute pain group than in the other two groups (mean [interquartile range]: 10.7 [3.3, 29.3] vs 1 [0.5, 3.8]mg/l; P < 0.001), suggesting that elevated preoperative plasma levels of CRP were associated with delirium. CONCLUSIONS: Preoperative acute pain was associated with POD, and increased plasma levels of CRP provide a marker. In addition, we found that illiteracy and advanced age were risk factors for POD.


Assuntos
Dor Aguda , Delírio , Dor Aguda/diagnóstico , Dor Aguda/epidemiologia , Proteína C-Reativa , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Humanos , Complicações Pós-Operatórias , Fatores de Risco
10.
J Cell Physiol ; 234(6): 8659-8667, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-29226319

RESUMO

The study was used to probe long noncoding RNA X-inactive specific transcript (lncRNA XIST) RNA expression profile and its influence on cell cycle, proliferation, and apoptosis in myocardial cells. We also aimed to explore the possible meditating relationship between XIST, PDE4D, and miR-130a-3p. Gene differential analysis was carried out using human lncRNA Microarray V3.0. quantitative real-time PCR was used to test mRNA expressions of XIST, miR-130a-3p, and PDE4D in normal cells and postmyocardial infarction (MI) cells. Western blot was applied to determine the protein expression profile of PED4D. Changes in viability and cell cycle/apoptosis of post-MI myocardial cells after silencing of XIST or PDE4D were investigated by MTT assay and flow cytometry, respectively. The targeting relationship between miR-130a-3p and XIST, PDE4D in myocardial cells were verified by dual luciferase reporter assay. Simulated MI environment was constructed by performing anoxic preconditioning in normal cells to probe the influence of XIST on myocardial cell apoptosis. XIST and PDE4D were overexpressed in post-MI myocardial cells, whereas miR-130a-3p was underexpressed in post-MI myocardial cells. High-expressed XIST and PDE4D both promoted myocardial cell apoptosis. High-expressed XIST also inhibited myocardial cell proliferation. XIST-downregulated miR-130a-3p and PDE4D was a direct target of miR-130a-3p. LncRNA XIST promotes MI by targeting miR-130a-3p. MI induced by PDE4D can be reversed by miR-130a-3p.


Assuntos
MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , RNA Longo não Codificante/metabolismo , Apoptose , Ciclo Celular , Hipóxia Celular , Linhagem Celular , Proliferação de Células , Microambiente Celular , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Regulação da Expressão Gênica , Humanos , MicroRNAs/genética , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miócitos Cardíacos/patologia , RNA Longo não Codificante/genética , Transdução de Sinais
11.
Vascul Pharmacol ; 116: 24-35, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-28694128

RESUMO

Pulmonary arterial hypertension (PAH) is a pathological condition characterized by excessive cell proliferation and migration of pulmonary arterial smooth muscle cells (PASMC). PAH pathogenesis shares similarities with cancers such as excessive cell proliferation and apoptosis resistance. A previous study by our group revealed that decreased expression of a tumor suppressor-AXIN2 (Axis inhibition protein 2) was responsible for enhanced PASMC proliferation and suppressed apoptosis. Nevertheless, the mechanisms that regulate the downregulation of AXIN2 in PAH remain elusive. Data from the present study demonstrated that miR-221-3p acts as an upstream regulator of AXIN2 and functions to induce PASMC proliferation. We first showed that miR-221-3p expression was elevated in lung tissue and PASMC of PAH patients as well as in animal models of PAH. Human PASMC were transfected with a miR-221-3p mimic and miR-221-3p inhibitor, respectively, and their effects on the proliferation and migration was assessed using BrdU incorporation, PCNA staining and wound healing assays. In addition, we investigated the molecular mechanism through which miR-221-3p contributes to cell proliferation in PASMC and identified AXIN2 as a direct target gene of miR-221-3p by dual luciferase reporter gene assays, qRT-qPCR and western blotting. Furthermore, we found that ectopic expression of AXIN2 or pharmacological inhibition of ß-catenin by XAV-939 can attenuate the effect of miR-221-3p on cell proliferation in PASMC. Moreover, intravenous injection of miR-221-3p inhibitor attenuated the progression of SU5416-hypoxia-induced PAH in rats. The results of the present study identified a new regulatory axis in which miR-221-3p and AXIN2 regulate the proliferation of PASMC.


Assuntos
Proteína Axina/metabolismo , Proliferação de Células , Hipertensão Pulmonar/metabolismo , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Remodelação Vascular , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Animais , Proteína Axina/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Estudos de Casos e Controles , Movimento Celular , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/prevenção & controle , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , beta Catenina/genética , beta Catenina/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-30519268

RESUMO

Our previous study has demonstrated that 6-Gingerol (6-G) could alleviate myocardial ischemia/reperfusion injury (MIRI). However, the molecular mechanism underlying the process of myocardial ischemia/reperfusion (I/R) injury alleviation by 6-G remains unelucidated. The objective of the present study is to further investigate the potential mechanism for 6-G to alleviate MIRI in rats. Thirty-two Sprague-Dawley rats were randomly divided into four groups: the Sham group, the I/R group, the 6-G + I/R group, and the LY294002 (LY) + 6-G + I/R group. For the rats in each of the groups, data were collected for cardiogram, cardiac function, area of myocardial infarction, myocardial pathology, myocardial enzyme, marker of inflammatory response, and PI3K/Akt signaling pathway. We found that the pretreatment of 6-G with 6 mg/kg could shrink the ST section of cardiogram, improve the cardiac function, reduce the area of myocardial infarction and the degree of cardiac pathological injury, lower the level of myocardial enzyme, and inhibit the inflammatory response. In addition, our results also indicated that 6-G could upregulate the expression of PI3K and p-Akt and that LY294002, a blocking agent of PI3K/Akt signaling pathway, could nullify the protecting role of 6-G. Our experimental results showed that 6-G could inhibit I/R-induced inflammatory response through the activation of the PI3K/Akt signaling pathway.

13.
J Hypertens ; 35(12): 2419-2435, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28704260

RESUMO

OBJECTIVE: Similar to cancer, pulmonary arterial hypertension (PAH) is characterized by vascular remodeling, which leads to obliteration of the small pulmonary arteriole, with marked proliferation of pulmonary artery smooth muscle cells (PASMC) and/or endothelial cells dysfunction. Aberrant expression of tumor suppressor genes is closely associated with susceptibility to PAH. We hypothesized that α-solanine, a glycoalkaloid found in members of the nightshade family known to have antitumor activity in different cancers, reverses experimental PAH by activating the tumor suppressor-axis inhibition protein 2 (AXIN2). METHODS AND RESULTS: We investigated the effects of α-solanine on PASMC proliferation and apoptosis by using 5-ethynyl-2'-deoxyuridine proliferation assay, proliferating cell nuclear antigen and Ki67 staining, TUNEL and Anexine V assays. Scratch wound healing and tube formation assays were also used to study migration of endothelial cells. In vitro, we demonstrated, using cultured human PASMC from PAH patients, that α-solanine reversed dysfunctional AXIN2, ß-catenin and bone morphogenetic protein receptor type-2 signaling, whereas restored [Ca]i, IL-6 and IL-8, contributing to the decrease of PAH-PASMC proliferation and resistance to apoptosis. Meanwhile, α-solanine inhibits proliferation, migration and tube formation of PAH-pulmonary artery endothelial cells by inhibiting Akt/GSK-3α activation. In vivo, α-solanine administration decreases distal pulmonary arteries remodeling, mean pulmonary arteries pressure and right ventricular hypertrophy in both monocrotaline-induced and Sugen/hypoxia-induced PAH in mice. CONCLUSION: This study demonstrates that AXIN2/ß-catenin axis and Akt pathway can be therapeutically targeted by α-solanine in PAH. α-Solanine could be used as a new therapeutic strategy for the treatment of PAH.


Assuntos
Hipertensão Pulmonar/metabolismo , Neovascularização Patológica/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Solanina/farmacologia , Remodelação Vascular/efeitos dos fármacos , Animais , Células Cultivadas , Humanos , Camundongos , Artéria Pulmonar/citologia , Artéria Pulmonar/metabolismo
14.
Vascul Pharmacol ; 87: 230-241, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27871853

RESUMO

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by remodeling of the pulmonary vasculature, including marked proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Members of the nuclear receptor 4A (NR4A) subfamily are involved in a variety of biological events, such as cell apoptosis, proliferation, inflammation, and metabolism. Activation of Nur77 (an orphan nuclear receptor that belongs to NR4A subfamily) has recently been reported to be as a beneficial agent in the treatment of cardiovascular and metabolic diseases. In the present study, we investigated the effects of NR4A on human PASMCs function in vitro and determined the underlying mechanisms. We found a robust expression of NR4A receptors in lung tissues of PAH patients and hypoxic mice but a highly significant downregulation within pulmonary arteries (PAs) as assessed by quantitative polymerase chain reaction, immunoblotting, and immunohistochemistry. In vitro, NR4A receptors were found significantly decreased in PASMCs derived from PAH patients. To explore the pathological effects of decreased Nur77 in PASMCs, PASMCs were transduced with siRNA against Nur77. The siRNA-mediated knockdown of Nur77 significantly augmented PASMCs proliferation and migration. In contrast, Nur77 overexpression prevented PASMCs from proliferation and migration. Mechanistically, overexpression of Axis inhibition protein 2 (Axin2) or inhibition of ß-catenin signaling was shown to be responsible for Nur77 knockdown-induced proliferation of PASMCs. Following hypoxia-induced angiogenesis of the pulmonary artery in C57BL/6 mice, small-molecule Nur77 agonists-Octaketide Cytosporone B (Csn-B) can significantly decreased thickness of vascular wall and markedly attenuated the development of chronic hypoxia-induced PAH in vivo. Therefore, reconstitution of Nur77 levels represents a promising therapeutic option to prevent vascular remodeling processes.


Assuntos
Proteína Axina/genética , Hipertensão Pulmonar/fisiopatologia , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , beta Catenina/metabolismo , Animais , Apoptose/genética , Movimento Celular/genética , Proliferação de Células/genética , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Hipertensão Pulmonar/genética , Hipóxia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/metabolismo , RNA Interferente Pequeno/administração & dosagem , Transdução de Sinais/genética , Remodelação Vascular/genética
15.
J Hypertens ; 34(5): 877-92, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26882042

RESUMO

OBJECTIVE: Pulmonary arterial hypertension (PAH) is characterized by increased vascular tone, altered vasoreactivity and vascular remodeling induced by smooth muscle cell proliferation. Similarities exist between cancer and PAH. Aberrant expression of the tumor suppressor protein is closely associated with PAH. Here, we tested the hypothesis that a tumor suppressor-axis inhibition protein 2 (Axin2) deficiency leads to PAH. METHODS AND RESULTS: We measured right ventricular systolic pressure in Axin2 knockout mice and assessed the expression of Axin2 in patients. We found that Axin2 expression level was decreased in both mice exposed to chronic hypoxia and patients with PAH in remodeled pulmonary arterioles. Axin2 knockout mice showed elevated mean right ventricular systolic pressure and enhanced contraction in response to phenylephrine. An increase in the cross-sectional area of the vessels was occupied by the vessel wall, indicating pulmonary vascular remodeling. Furthermore, knocking down Axin2 with small interfering RNA inhibited apoptosis of pulmonary arterial smooth muscle cells (PASMCs). This inhibition was significantly abolished by ß-catenin inhibitors, indicating that Axin2 through ß-catenin increased vascular wall by inhibiting the apoptosis of PASMCs. Importantly, overexpression of Axin2 attenuates the development of hypoxia-induced PAH in mice. CONCLUSION: Taken together, our study, for the first time, established that Axin2 plays a key role in the progression of PAH. We identified Axin2 as a novel mediator of pulmonary vasoconstriction and PASMC growth in hypoxia-mediated PAH. Our results suggest that downregulation of Axin2 in the pulmonary vasculature may be an underlying mechanism in the development of hypoxia-induced PAH.


Assuntos
Proteína Axina/metabolismo , Hipertensão Pulmonar/fisiopatologia , beta Catenina/metabolismo , Animais , Proteína Axina/antagonistas & inibidores , Proteína Axina/sangue , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Humanos , Hipertensão Pulmonar/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Músculo Liso Vascular/metabolismo , Transdução de Sinais
17.
Chin J Nat Med ; 11(5): 525-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24359778

RESUMO

AIM: To study the chemical constituents of the flowers of Rhododendron molle. METHODS: Compounds were isolated by repeated chromatography over silica gel and Sephadex LH-20. Structures were elucidated based on spectral techniques, mainly 1D- and 2D-NMR and mass spectrometric analyses. RESULTS: Two compounds (1 and 2) were isolated. CONCLUSIONS: Compounds 1 and 2 were identified as two new compounds: 2α, 10α-epoxy-3ß, 5ß, 6ß, 14ß, 16α-hexahydroxy-grayanane and benzyl 2, 6-dihydroxybenzoate-6-O-α-L-rhamnopyranosyl-(1→3)-ß-D-glucopyranoside, respectively.


Assuntos
Medicamentos de Ervas Chinesas/química , Flores/química , Rhododendron/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular
18.
Molecules ; 18(3): 2840-50, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23455673

RESUMO

Two new limonoids, toonins A (1) and B (2), and one new dihydrobenzofuran norlignan, toonin C (3), were isolated from the roots of Toona sinensis together with the ten known compounds 4-methoxy-6-(2',4'-dihydroxy-6'-methylphenyl)-pyran-2-one (4), bourjotinolone A (5), proceranone (6), matairesinol (7), 4-hydroxy-3-methoxybenzene-ethanol (8), syringic acid (9), isoscopoletin (10), lyoniresinol (11), aloeemodin (12), and ß-sitosterol (13). Their structures were elucidated on the basis of one- and two-dimensional spectroscopic analysis. Isolation of compounds 4, 6-13 from this plant is reported here for the first time.


Assuntos
Cedrela/química , Limoninas/química , Raízes de Plantas/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Limoninas/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Estereoisomerismo
19.
PLoS One ; 8(3): e57864, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23526953

RESUMO

The natural flavone acacetin has been demonstrated to inhibit transient outward potassium current (Ito) in human atrial myocytes. However, the molecular determinants of acacetin for blocking Ito are unknown. The present study was designed to investigate the properties and molecular determinants of this compound for blocking hKv4.3 channels (coding Ito) stably expressed in HEK 293 cells using the approaches of whole-cell patch voltage-clamp technique and mutagenesis. It was found that acacetin inhibited hKv4.3 current by binding to both the closed and open channels, and decreased the recovery from inactivation. The blockade of hKv4.3 channels by acacetin was use- and frequency-dependent, and IC50s of acacetin for inhibiting hKv4.3 were 7.9, 6.1, 3.9, and 3.2 µM, respectively, at 0.2, 0.5, 1, and 3.3 Hz. The mutagenesis study revealed that the hKv4.3 mutants T366A and T367A in the P-loop helix, and V392A, I395A and V399A in the S6-segment had a reduced channel blocking efficacy of acacetin (IC50, 44.5 µM for T366A, 25.8 µM for T367A, 17.6 µM for V392A, 16.2 µM for I395A, and 19.1 µM for V399A). These results demonstrate the novel information that acacetin may inhibit the closed channels and block the open state of the channels by binding to their P-loop filter helix and S6 domain. The use- and rate-dependent blocking of hKv4.3 by acacetin is likely beneficial for managing atrial fibrillation.


Assuntos
Flavonas/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio Shal/antagonistas & inibidores , Sítios de Ligação/genética , Flavonas/metabolismo , Células HEK293 , Humanos , Cinética , Mutagênese Sítio-Dirigida , Técnicas de Patch-Clamp , Bloqueadores dos Canais de Potássio/metabolismo , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Canais de Potássio Shal/genética , Canais de Potássio Shal/metabolismo
20.
Fitoterapia ; 84: 54-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23103953

RESUMO

An alkaloid with novel skeleton, sinoscrewtine (1), has been isolated from the roots of Sinomenium acutum. Its structure was established by spectral analysis and X-ray crystallographic study, and its possible biosynthetic pathway was delivered. In vitro experiments, 1 showed weak injurious effects against H(2)O(2)/Aß(25-35) induced oxidative injury in PC-12 cells and DPPH radical scavenging activity with IC(50) of 32.6µM.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Raízes de Plantas/química , Sinomenium/química , Animais , Modelos Moleculares , Estrutura Molecular , Células PC12 , Ratos
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