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1.
Sheng Li Xue Bao ; 71(6): 824-832, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31879737

RESUMO

Drugs of abuse leads to adaptive changes in the brain stress system, and produces negative affective states including aversion and anxiety after drug use is terminated. Corticotrophin-releasing hormone (CRH) is the main transmitter in control of response to stressors and is neuronal enriched in the central amygdala (CeA), a sub-region of the extended amygdala playing an important role in integrating emotional information and modulating stress response. The effect of CRH neurons in CeA on the negative emotions on morphine naïve and withdrawal mice is unclear. Thus, we utilized CRH-Cre transgenic mice injected with AAV-mediated Designer Receptors Exclusively Activated By Designer Drugs (DREADDs) to chemogenetically manipulate CRH neurons in CeA. And methods of behavior analysis, including conditioned place aversion (CPA), elevated plus maze and locomotor activity tests, were used to investigate morphine withdrawal-induced negative emotions in mice. The results showed that, inhibiting CRH neurons of CeA decreased the formation of morphine withdrawal-induced CPA, as well as the anxiety level of CRH-Cre mice. Furthermore, specifically activating CRH neurons in CeA evoked CPA and anxiety of morphine naïve mice. Neither inhibiting nor activating CRH neurons had effects on their locomotor activity. These results suggest that CRH neurons in CeA are involved in the mediation of morphine withdrawal-induced negative emotion in mice, providing a theoretical basis for drug addiction and relapse mechanism.


Assuntos
Núcleo Central da Amígdala , Emoções , Morfina , Neurônios , Hormônio Adrenocorticotrópico , Animais , Hormônio Liberador da Corticotropina/metabolismo , Emoções/fisiologia , Camundongos , Morfina/metabolismo , Neurônios/metabolismo
2.
Molecules ; 25(1)2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31878239

RESUMO

DJ-1 was recently reported to be involved in the cardioprotection of hypoxic preconditioning (HPC) against hypoxia/reoxygenation (H/R)-induced oxidative stress damage, by preserving mitochondrial complex I activity and, subsequently, inhibiting mitochondrial reactive oxygen species (ROS) generation. However, the molecular mechanism by which HPC enables mitochondrial translocation of DJ-1, which has no mitochondria-targeting sequence, to preserve mitochondrial complex I, is largely unknown. In this study, co-immunoprecipitation data showed that DJ-1 was associated with glucose-regulated protein 75 (Grp75), and this association was significantly enhanced after HPC. Immunofluorescence imaging and Western blot analysis showed that HPC substantially enhanced the translocation of DJ-1 from cytosol to mitochondria in H9c2 cells subjected to H/R, which was mimicked by DJ-1 overexpression induced by pFlag-DJ-1 transfection. Importantly, knockdown of Grp75 markedly reduced the mitochondrial translocation of DJ-1 induced by HPC and pFlag-DJ-1 transfection. Moreover, HPC promoted the association of DJ-1 with mitochondrial complex I subunits ND1 and NDUFA4, improved complex I activity, and inhibited mitochondria-derived ROS production and subsequent oxidative stress damage after H/R, which was also mimicked by pFlag-DJ-1 transfection. Intriguingly, these effects of HPC and pFlag-DJ-1 transfection were also prevented by Grp75 knockdown. In conclusion, these results indicated that HPC promotes the translocation of DJ-1 from cytosol to mitochondria in a Grp75-dependent manner and Grp75 is required for DJ-1-mediated protection of HPC on H/R-induced mitochondrial complex I defect and subsequent oxidative stress damage.

3.
Eur J Pharmacol ; 863: 172701, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31568784

RESUMO

Myocardial ischemia/reperfusion (IR) injury is caused by the restoration of the coronary blood flow following an ischemic episode. Accumulating evidence suggests that galectin-3, a ß-galactoside-binding lectin, acts as a biomarker in heart disease. However, it remains unclear whether manipulating galectin-3 affects the susceptibility of the heart to IR injury. In this study, RNA sequencing (RNA-seq) analysis identified that Lgals3 (galecin-3) plays an indispensable role in IR-induced cardiac damage. Immunostaining and immunoblot assays confirmed that the expression of galectin-3 was markedly increased in myocardial IR injury both in vivo and in vitro. Echocardiographic analysis showed that cardiac dysfunction in experimental IR injury was significantly attenuated by galectin-3 inhibitors including pectin (1%, i.p.) from citrus and binding peptide G3-C12 (5.0 mg/kg, i.p.). Galectin-3 inhibitor-treated mice exhibited smaller infarct sizes and decreased tissue injury. Furthermore, TUNEL staining showed that galectin-3 inhibition suppressed IR-mediated cardiomyocyte apoptosis. Mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) levels were well-preserved and IR-induced changes of mitochondrial cyto c, cytosol cyto c, caspase-9, caspase-3, Bcl-2 and Bax in the galectin-3 inhibitor-treated groups were observed. Our findings indicate that the pathological upregulation of galectin-3 contributes to IR-induced cardiac dysfunction and that galectin-3 inhibition ameliorates myocardial injury, highlighting its therapeutic potential.

5.
Toxicol Appl Pharmacol ; 369: 60-72, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30831131

RESUMO

Hypoxic pulmonary vasoconstriction (HPV) can be modulated by Rho/Rho kinase signaling, which can alter HPV vascular function via regulating myosin light chain phosphorylation, in a manner generally believed to be Ca2+-independent. We hypothesized that the RhoA/ROCK signaling pathway also can regulate HPV vascular function via a Ca2+-dependent mechanism, signaling through the functional transient receptor potential canonical (TRPC) channels. In this study, male BALB/c mice were exposed to normoxic or 10% oxygen (hypoxic) conditions for six weeks, after which systolic pressure and right ventricular hypertrophy were assessed. Transient intracellular calcium was monitored using a fluorescence imaging system. Muscle tension was measured with a contractile force recording system, and protein expression was assessed by immunoblotting. We found that the expressions of RhoA and ROCK were increased in mouse pulmonary arteries (PAs) under conditions of chronic hypoxia. Inhibition of the RhoA/ROCK signaling pathway prevented the development of hypoxic pulmonary hypertension (HPH), as evidenced by significantly reduced PA remodeling and pulmonary vasoconstriction. Immunoblotting results revealed that inhibition of the RhoA/ROCK signaling pathway significantly decreased the expression of HIF-1α. Knockdown of HIF-1α down-regulated the expression and function of the TRPC1 and TRPC6 channels in PASMCs under conditions of hypoxia. Contraction of the PAs and a Ca2+ influx into PASMCs through either receptor- or store-operated Ca2+ channels were also increased after hypoxia. However, RhoA/ROCK inhibitors markedly attenuated these changes. These results indicate that inhibition of the RhoA/ROCK signaling pathway ameliorates HPH via HIF-1α-dependent functional TRPCs.

6.
Toxicol Appl Pharmacol ; 368: 26-36, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30776389

RESUMO

Cardiac dysfunction is a vital complication during endotoxemia (ETM). Accumulating evidence suggests that enhanced glycolytic metabolism promotes inflammatory and myocardial diseases. In this study, we performed deep mRNA sequencing analysis on the hearts of control and lipopolysaccharide (LPS)-challenged mice (40 mg/kg, i.p.) and identified that the glycolytic enzyme, 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase 3 (PFKFB3) might play an indispensable role in ETM-induced cardiac damage. Quantitative real-time PCR validated the transcriptional upregulation of PFKFB3 in the myocardium of LPS-challenged mice and immunoblotting and immunostaining assays confirmed that LPS stimulation markedly increased the expression of PFKFB3 at the protein level both in vivo and in vitro. The potent antagonist 3-(3pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) was used to block PFKFB3 activity in vivo (50 mg/kg, i.p.) and in vitro (10 µM). Echocardiographic analysis and TUNEL staining showed that 3PO significantly alleviated LPS-induced cardiac dysfunction and apoptotic injury in vivo. 3PO also suppressed the LPS-induced secretion of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6 and lactate in the serum, in addition to lactate in the myocardium. PFKFB3 inhibition also diminished the nuclear translocation and phosphorylation of transcription factor nuclear factor-κB (NF-κB) in both adult cardiomyocytes and HL-1 cells. Furthermore, immunoblotting analysis showed that 3PO inhibited LPS-induced apoptotic induction in cardiomyocytes. Taken together, these findings demonstrate that PFKFB3 participates in LPS-induced cardiac dysfunction via mediating inflammatory and apoptotic signaling pathway.

7.
Sheng Li Xue Bao ; 70(5): 463-473, 2018 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-30377684

RESUMO

Drug addiction is a chronic psychiatric disorder characterized by compulsive drug taking, and involves neuronal plasticity changes in multiple brain regions. The prelimbic cortex (PrL) is a key region of the dorsomedial prefrontal cortex and contains majority of pyramidal neurons. The excitatory projections from PrL play a very important role in the drug seeking behaviors. PrL also contains a small amount of GABAergic interneurons, which regulate the information integration and transmission of the pyramidal neurons. However, the roles of the GABAergic interneurons in PrL in drug-induced behavior changes are not clear. In the PrL, parvalbumin (PV) and somatostatin (SST) interneurons are two major GABAergic interneurons, which have been reported to regulate the activity of glutamatergic input, and form inhibitory synaptic transmission to regulate the output of downstream signals. Here, we used PV-Cre and SST-Cre mice combined with chemical genetics to explore the role of PV and SST interneurons in PrL in morphine-induced behavior changes. Our data showed that specific inhibiting SST interneurons in PrL significantly increased the anxiety level and decreased morphine-induced locomotor activity and the conditioned place preference (CPP) score. Instead, specific inhibiting PV interneurons in PrL had no effect on the anxiety level, morphine induced-locomotor activity and CPP. Our findings provide a new insight into the cellular and neuronal specific mechanism for drug addiction.


Assuntos
Comportamento de Procura de Droga , Interneurônios/efeitos dos fármacos , Morfina/farmacologia , Parvalbuminas , Córtex Pré-Frontal/citologia , Somatostatina , Animais , Comportamento Animal , Encéfalo , Condicionamento Clássico , Interneurônios/citologia , Camundongos , Plasticidade Neuronal , Córtex Pré-Frontal/efeitos dos fármacos , Células Piramidais/citologia , Transmissão Sináptica
8.
J Headache Pain ; 19(1): 102, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30400767

RESUMO

BACKGROUND: Although the mechanism of chronic migraine (CM) is unclear, it might be related to central sensitization and neuronal persistent hyperexcitability. The tyrosine phosphorylation of NR2B (NR2B-pTyr) reportedly contributes to the development of central sensitization and persistent pain in the spinal cord. Central sensitization is thought to be associated with an increase in synaptic efficiency, but the mechanism through which NR2B-pTyr regulates synaptic participation in CM-related central sensitization is unknown. In this study, we aim to investigate the role of NR2B-pTyr in regulating synaptic plasticity in CM-related central sensitization. METHODS: Male Sprague-Dawley rats were subjected to seven inflammatory soup (IS) injections to model recurrent trigeminovascular or dural nociceptor activation, which is assumed to occur in patients with CM. We used the von Frey test to detect changes in mechanical withdrawal thresholds, and western blotting and immunofluorescence staining assays were performed to detect the expression of NR2B-pTyr in the trigeminal nucleus caudalis (TNC). NR2B-pTyr was blocked with the Src family kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)-pyrazolo [3,4-d] pyrimidine (PP2) and the protein tyrosine kinase inhibitor genistein to detected the changes in calcitonin gene-related peptide (CGRP), substance P (SP), and the synaptic proteins postsynaptic density 95 (PSD95), synaptophysin (Syp), synaptotagmin1 (Syt-1). The synaptic ultrastructures were observed by transmission electron microscopy (TEM), and the dendritic architecture of TNC neurons was observed by Golgi-Cox staining. RESULTS: Statistical analyses revealed that repeated infusions of IS induced mechanical allodynia and significantly increased the expression of NR2B Tyr-1472 phosphorylation (pNR2B-Y1472) and NR2B Tyr-1252 phosphorylation (pNR2B-Y1252) in the TNC. Furthermore, the inhibition of NR2B-pTyr by PP2 and genistein relieved allodynia and reduced the expression of CGRP, SP, PSD95, Syp and Syt-1 and synaptic transmission. CONCLUSIONS: These data indicate that NR2B-pTyr might regulate synaptic plasticity in central sensitization in a CM rat model. The inhibition of NR2B tyrosine phosphorylation has a protective effect on threshold dysfunction and migraine attacks through the regulation of synaptic plasticity in central sensitization.


Assuntos
Sensibilização do Sistema Nervoso Central/fisiologia , Modelos Animais de Doenças , Transtornos de Enxaqueca/metabolismo , Plasticidade Neuronal/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Tirosina/metabolismo , Animais , Hiperalgesia/metabolismo , Hiperalgesia/patologia , Masculino , Transtornos de Enxaqueca/patologia , Neurônios/metabolismo , Neurônios/patologia , Dor/metabolismo , Dor/patologia , Fosforilação/fisiologia , Ratos , Ratos Sprague-Dawley , Núcleo Inferior Caudal do Nervo Trigêmeo/metabolismo , Núcleo Inferior Caudal do Nervo Trigêmeo/patologia
9.
Huan Jing Ke Xue ; 39(2): 585-591, 2018 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964819

RESUMO

From March 2013 to December 2014, we on-site inspected indoor concentrations of formaldehyde and a benzene series in 454 children's bedrooms that were decorated earlier than one year before our inspection. Large differences existed in the formaldehyde and benzene-series concentrations among individual bedrooms. Bedrooms that were inspected in winter had significantly higher concentration of formaldehyde than bedrooms that were inspected in other seasons (P<0.001), but the benzene-series concentration had no significant seasonal difference. Among bedrooms that were inspected in spring, those using different materials as wall coverings had significant differences in concentrations of the benzene series. Among bedrooms that were inspected in summer, those using different materials as floor coverings had significant differences in concentrations of the benzene series (P<0.01). Among bedrooms that were inspected in autumn, those with>5 household bonsais had significantly higher concentrations of formaldehyde than other bedrooms did. Among bedrooms that were inspected in winter, those with frequent use of air humidifiers and those in which pets were kept had significantly higher concentrations of the benzene series than other bedrooms did (P<0.05). These results indicate that, after a long time since decoration, the types of household wall and floor covering materials still have certain relationships with indoor benzene-series levels and, compared to decoration materials, household ventilation perhaps has greater effect on indoor formaldehyde levels. The indoor benzene-series level perhaps has associations with indoor humidity level and the keeping of pets in households. Household bonsaies may have limited effect on indoor formaldehyde and benzene-series levels in residences that were decorated a long time ago.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Benzeno/análise , Formaldeído/análise , Habitação , Animais , Criança , China , Pisos e Cobertura de Pisos , Humanos , Animais de Estimação , Estações do Ano
10.
Bioorg Med Chem Lett ; 28(10): 1943-1948, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29650291

RESUMO

A series of N-sulfonaminoethyloxime derivatives of dehydroabietic acid were synthesized and investigated for their antibacterial activity against Staphylococcus aureus Newman strain and multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108 and NRS-271). Most of the target compounds having chloro, bromo, trifluoromethyl phenyl moiety exhibited potent in vitro antistaphylococcal activity. The meta-CF3 phenyl derivative T23 showed the highest activity with MIC of 0.39-0.78 µg/mL against S. aureus Newman, while several analogues showed similar potent antibacterial activity with MIC values between 0.78 and 1.56 µg/mL against five multidrug-resistant S. aureus. The stability of T35 in plasma of SD rat and the cellular cytotoxicity were also evaluated.


Assuntos
/química , Antibacterianos/síntese química , Oximas/química , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Estabilidade de Medicamentos , Testes de Sensibilidade Microbiana , Oximas/metabolismo , Oximas/farmacologia , Ratos , Ratos Sprague-Dawley , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade
11.
Toxicol Appl Pharmacol ; 341: 56-63, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29355567

RESUMO

BACKGROUND: Atherosclerosis is characterized by chronic inflammation in vascular wall. Previous studies suggest that Kuwanon G (KWG) exerts anti-inflammatory activities. However, the effect of KWG on atherosclerosis remains unexplored. AIMS: To explore whether KWG affects macrophage foam cell formation in vitro and atherogenesis in vivo. METHODS: RAW 264.7 macrophages were stimulated with ox-LDL for 24h to induce foam cell formation and treated with KWG. Foam cell formation was determined by ORO staining and enzymatic analysis. Pro-inflammatory cytokines mRNA levels were tested by Real-time PCR method. Further molecular mechanism was investigated using Western blot. In vivo, ApoE-/- mice were fed with high-fat diet and intraperitoneally injected with KWG. Atherosclerotic lesion was accessed by H&E and ORO staining. Plaque composition was evaluated by immunohistochemistry and Sirius Red staining. Serum lipid profile and inflammatory cytokines were evaluated by enzymatic method and ELISA. RESULTS: KWG significantly decreased intracellular lipid accumulation and inflammatory cytokines mRNA levels in macrophages through enhancing LXRα-ABCA1/ABCG1 pathway and inhibiting NFκB activation. Administrated with KWG remarkably reduced the atherosclerotic lesion areas and macrophage content in the plaque of high-fat diet fed ApoE-/- mice. KWG also reduced hyperlipidemia and serum inflammatory cytokines in vivo. CONCLUSION: Taken together, these data highlight that KWG can attenuate atherosclerosis through inhibiting foam cell formation and inflammatory response.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/biossíntese , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/biossíntese , Aterosclerose/metabolismo , Flavonoides/farmacologia , Receptores X do Fígado/biossíntese , Macrófagos/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Dieta Hiperlipídica/efeitos adversos , Relação Dose-Resposta a Droga , Flavonoides/uso terapêutico , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células RAW 264.7 , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(4): 463-469, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-28407837

RESUMO

OBJECTIVE: To study the effects of embryonic lead exposure on food intake and bowel movement in offspring rats and possible mechanisms. METHODS: Sprague-Dawley rats were given 0.1% (low-dose lead exposure group) or 0.2% (high-dose lead exposure group) lead acetate freely during pregnancy to establish an animal model of embryonic lead exposure. A blank control group was also established. The male offspring rats were enrolled in the study, and 10 male offspring rats from each group were selected to observe the changes in food intake, bowel movement, gastric emptying, intestine propulsion, and pathological inflammatory response in the gastric mucosa. Eight offspring rats were selected from each group, and electron microscopy and immunohistochemistry were used to observe the changes in the ultrastructure of jejunal microvilli and cell junction and the expression of cholecystokinin-8 (CCK-8) and motilin (MTL) in the feeding center, in order to reveal the possible mechanisms for abnormal gastrointestinal motility in offspring rats induced by embryonic lead exposure. RESULTS: Compared with the control group, the low- and high-dose lead exposure groups had a significant reduction in daily food intake, a significant increase in water content of feces, a significant reduction in fecal pellet weight, and a significant increase in small intestine propulsion (P<0.05). The high-dose lead exposure group had a significant reduction in gastric emptying ability compared with the control group (P<0.05). Compared with the control group, the lead exposure groups had significantly greater pathological inflammatory changes in the gastric mucosa (P<0.05), significant reductions in the number and length of the jejunal microvilli and the number of epithelial desmosome junctions (P<0.05), a significant increase in the macula densa gap (P<0.05), and significant increases in the expression of MTL and CCK-8 in the feeding center (P<0.05), in a dose-dependent manner. CONCLUSIONS: The degree of gastrointestinal structural injury and expression levels of MTL and CCK-8 in the feeding center are lead dose-dependent, which may be important mechanisms for changes in food intake, bowel movement, and digestive functions in offspring rats induced by embryonic lead exposure.


Assuntos
Defecação/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feto/efeitos dos fármacos , Chumbo/toxicidade , Animais , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Jejuno/patologia , Ratos , Ratos Sprague-Dawley
13.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(3): 361-367, 2017 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-28302213

RESUMO

OBJECTIVE: To explore the effects of embryonic lead exposure on motor function and balance ability in offspring rats and the possible mechanisms. METHODS: An animal model of embryonic lead exposure was prepared with the use of pregnant Sprague-Dawley rats freely drinking 0.1% (low-dose group, LG) or 0.2% (high-dose group, HG) lead acetate solution. A normal control group (NG) was also set. The male offspring rats of these pregnant rats were included in the study, consisting of 12 rats in the NG group, 10 rats in the LG group, and 9 rats in the HG group. The offspring rats' motor function and balance ability were evaluated using body turning test and coat hanger test. Eight rats were randomly selected from each group, and immunohistochemistry and Timm's staining were employed to measure the expression of c-Fos and mossy fiber sprouting (MFS) in the hippocampus. RESULTS: The HG group had a significantly longer body turning time than the NG and LG groups (P<0.05), and the LG group had a significantly longer body turning time than the NG group (P<0.05). The HG group had a significantly lower score of balance ability than the NG and LG groups (P<0.05), and the LG group had a significantly lower score of balance ability than the NG group (P<0.05). The area percentage of c-Fos-positive neurons in the hippocampal CA1 region was significantly higher in the HG group than in the other two groups (P<0.05), and it was significantly higher in the LG group than in the NG group (P<0.05). The semi-quantitative scores of MFS in the hippocampal CA3 region and dentate gyrus were significantly higher in the HG group than in the other two groups (P<0.05), and they were significantly higher in the LG group than in the NG group (P<0.05). CONCLUSIONS: Embryonic lead exposure could impair the offspring rats' motor function and balance ability. These changes may be related to increased c-Fos expression in the hippocampal CA3 region and abnormal MFS in the hippocampal CA3 region and dentate gyrus.


Assuntos
Feto/efeitos dos fármacos , Chumbo/toxicidade , Atividade Motora/efeitos dos fármacos , Equilíbrio Postural/efeitos dos fármacos , Animais , Feminino , Hipocampo/química , Hipocampo/efeitos dos fármacos , Masculino , Fibras Musgosas Hipocampais/efeitos dos fármacos , Gravidez , Proteínas Proto-Oncogênicas c-fos/análise , Ratos , Ratos Sprague-Dawley
14.
Biomol Ther (Seoul) ; 25(3): 279-287, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-27737525

RESUMO

The chemical property of cinnamaldehyde is unstable in vivo, although early experiments have shown its obvious therapeutic effects on viral myocarditis (VMC). To overcome this problem, we used cinnamaldehyde as a leading compound to synthesize derivatives. Five derivatives of cinnamaldehyde were synthesized: 4-methylcinnamaldehyde (1), 4-chlorocinnamaldehyde (2), 4-methoxycinnamaldehyde (3), α-bromo-4-methylcinnamaldehyde (4), and α-bromo-4-chlorocinnamaldehyde (5). Neonatal rat cardiomyocytes and HeLa cells infected by coxsackievirus B3 (CVB3) were used to evaluate their antiviral and cytotoxic effects. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. Among the derivatives, compound 4 and 5 inhibited the CVB3 in HeLa cells with the half-maximal inhibitory concentrations values of 11.38 ± 2.22 µM and 2.12 ± 0.37 µM, respectively. The 50% toxic concentrations of compound 4 and 5-treated cells were 39-fold and 87-fold higher than in the cinnamaldehyde group. Compound 4 and 5 effectively reduced the viral titers and cardiac pathological changes in a dose-dependent manner. In addition, compound 4 and 5 significantly inhibited the secretion, mRNA and protein expressions of inflammatory cytokines TNF-α, IL-1ß and IL-6 in CVB3-infected cardiomyocytes, indicating that brominated cinnamaldehyde not only improved the anti-vital activities for VMC, but also had potent anti-inflammatory effects in cardiomyocytes induced by CVB3.

15.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(5): 440-5, 2016 May.
Artigo em Chinês | MEDLINE | ID: mdl-27165595

RESUMO

OBJECTIVE: To study the effect of cyclooxygenase -2 selective inhibitor celecoxib on the expression of major vault protein ( MVP) in the brain of rats with status epilepticus and its possible roles in the treatment of refractory epilepsy. METHODS: Sixty adult male Sprague-Dawley rats were randomly assigned to blank control (n=16), epilepsy model (n=22) and celecoxib treatment groups (n=22). After the status epilepticus was induced in rats by injecting lithium and pilocarpine, each group had 16 rats enrolled as subjects. Immunohistochemical method and Western blot method were used to detect the expression of MVP in the frontal cortex and hippocampus. RESULTS: The expression of MVP was significantly higher in the epilepsy model group than in the control group (P<0.01). The expression of MVP in the celecoxib treatment group was significantly decreased compared with the epilepsy model group, but it was still higher than in the control group (P<0.01). CONCLUSIONS: Celecoxib could decrease the expression of MVP in brain tissue of rats with status epilepticus, suggesting that it is promising for the treatment of intractable epilepsy.


Assuntos
Celecoxib/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Estado Epiléptico/tratamento farmacológico , Partículas de Ribonucleoproteínas em Forma de Abóbada/análise , Animais , Western Blotting , Encéfalo/metabolismo , Celecoxib/uso terapêutico , Imuno-Histoquímica , Masculino , Ratos , Ratos Sprague-Dawley , Estado Epiléptico/metabolismo
16.
J Insect Sci ; 152015.
Artigo em Inglês | MEDLINE | ID: mdl-26494777

RESUMO

Sogatella furcifera (Horváth) is the most threatening migratory rice pest in Yunnan, China. S. furcifera overwinters in low- altitude basins and valleys in southern Yunnan and migrates northward in spring and summer of the following year, causing serious damage during migration. The overwintering distribution, areas, and spatial pattern of S. furcifera are relevant to the migration and outbreak of this pest. Based on a 4-yr field survey (2010-2013), this study projected areas suitable for S. furcifera to overwinter using a species distribution model, and analyzed the key influencing climatic factors using principal component analysis (PCA) and ecological niche factor analysis (ENFA). Our field survey showed that the northern latitudinal- and upper elevation limits of overwintering S. furcifera was 25.4° N and 1,608 m in western Yunnan and 24.2° N and 1,563 m in eastern Yunnan. The species distribution model produced a fragmented distribution pattern, with most of which in western Yunnan and only a few in eastern Yunnan. The PCA and ENFA analyses showed that the mean temperature of the driest quarter and the precipitation of the coldest quarter significantly influenced the distribution of S. furcifera in winter. The results suggested that the complex topography, spatial differences in winter temperatures, and host availability altogether determined the distribution of overwintering S. furcifera. Compared with previous surveys, the northern latitudinal- and upper elevation limits of overwintering S. furcifera were higher, while the population became rarer in some suitable areas due to change of farmland utilization in winter and possibly climate change.


Assuntos
Clima , Hemípteros/fisiologia , Oryza , Altitude , Distribuição Animal , Animais , China , Ecossistema , Análise de Componente Principal , Estações do Ano
17.
Neural Regen Res ; 10(4): 599-604, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26170821

RESUMO

Previous studies have shown that the long-term use of antiepileptic drugs can cause nervous system damage. However, short-term antiepileptic drug treatment is frequently given to infants, especially neonates, to control seizure. Whether the short-term use of antiepileptic drugs is neurotoxic remains unclear. In the present study, immature rats, 3-21 days of age, were intraperitoneally injected with phenobarbital and/or topiramate for 3 consecutive days. Hematoxylin-eosin and immunohistochemical staining revealed that phenobarbital and topiramate, individually or in combination, were cytotoxic to hippocampal CA1 neurons and inhibited the expression of GluR1 and NR2B, excitatory glutamate receptor subunits. Furthermore, the combination of the two drugs caused greater damage than either drug alone. The results demonstrate that the short-term use of antiepileptic drugs damages neurons in the immature brain and that the combined use of antiepileptic drugs exacerbates damage. Our findings suggest that clinicians should consider the potential neurotoxic risk associated with the combined use of antiepileptic drugs in the treatment of seizure.

18.
Angew Chem Int Ed Engl ; 54(32): 9313-8, 2015 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-26079517

RESUMO

Chemical synaptic transmission is central to the brain functions. In this regard, real-time monitoring of chemical synaptic transmission during neuronal communication remains a great challenge. In this work, in vivo-like oriented neural networks between superior cervical ganglion (SCG) neurons and their effector smooth muscle cells (SMC) were assembled in a microfluidic device. This allowed amperometric detection of individual neurotransmitter release events inside functional SCG-SMC synapse with carbon fiber nanoelectrodes as well as recording of postsynaptic potential using glass nanopipette electrodes. The high vesicular release activities essentially involved complex events arising from flickering fusion pores as quantitatively established based on simulations. This work allowed for the first time monitoring in situ chemical synaptic transmission under conditions close to those found in vivo, which may yield important and new insights into the nature of neuronal communications.


Assuntos
Potenciais Pós-Sinápticos Excitadores/fisiologia , Junção Neuromuscular/metabolismo , Sinapses/metabolismo , Animais , Células Cultivadas , Técnicas de Cocultura , Técnicas Eletroquímicas , Eletrodos , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Microscopia de Fluorescência , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Nanoestruturas/química , Junção Neuromuscular/química , Neurotransmissores/metabolismo , Gânglio Cervical Superior/citologia , Gânglio Cervical Superior/metabolismo , Transmissão Sináptica
19.
Lab Chip ; 15(4): 1178-87, 2015 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-25565271

RESUMO

Reproducing a tumor microenvironment consisting of blood vessels and tumor cells for modeling tumor invasion in vitro is particularly challenging. Here, we report an artificial blood vessel implanted 3D microfluidic system for reproducing transvascular migration of tumor cells. The transparent, porous and elastic artificial blood vessels are obtained by constructing polysaccharide cellulose-based microtubes using a chitosan sacrificial template, and possess excellent cytocompatibility, permeability, and mechanical characteristics. The artificial blood vessels are then fully implanted into the collagen matrix to reconstruct the 3D microsystem for modeling transvascular migration of tumor cells. Well-defined simulated vascular lumens were obtained by proliferation of the human umbilical vein endothelial cells (HUVECs) lining the artificial blood vessels, which enables us to reproduce structures and functions of blood vessels and replicate various hemodynamic parameters. Based on this model, the adhesion and transvascular migration of tumor cells across the artificial blood vessel have been well reproduced.


Assuntos
Órgãos Artificiais , Vasos Sanguíneos/citologia , Movimento Celular , Dispositivos Lab-On-A-Chip , Modelos Biológicos , Neoplasias/patologia , Microambiente Tumoral , Adesão Celular , Linhagem Celular Tumoral , Celulose/química , Quitosana/química , Humanos , Tamanho da Partícula , Porosidade , Propriedades de Superfície
20.
Chem Sci ; 6(3): 1853-1858, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28706641

RESUMO

It is a great challenge to develop electrochemical sensors with superior sensitivity that concurrently possess high biocompatibility for monitoring at the single cell level. Herein we report a novel and reusable biomimetic micro-electrochemical sensor array with nitric oxide (NO) sensing-interface based on metalloporphyrin and 3-aminophenylboronic acid (APBA) co-functionalized reduced graphene oxide (rGO). The assembling of high specificity catalytic but semi-conductive metalloporphyrin with high electric conductive rGO confers the sensor with sub-nanomolar sensitivity. Further coupling with the small cell-adhesive molecule APBA obviously enhances the cytocompatibility of the microsensor without diminishing the sensitivity, while the reversible reactivity between APBA and cell membrane carbohydrates allows practical reusability. The microsensor was successfully used to sensitively monitor, in real-time, the release of NO molecules from human endothelial cells being cultured directly on the sensor. This demonstrates its potential application in the detection of NO with very low bioactive concentrations for the better understanding of its physiological function and for medical tracking of patient states.

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