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1.
J Neurosci ; 43(16): 2907-2920, 2023 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-36868854

RESUMO

General anesthesia shares many similarities with natural sleep in behavior and electroencephalogram (EEG) patterns. The latest evidence suggests that general anesthesia and sleep-wake behavior may share overlapping neural substrates. The GABAergic neurons in the basal forebrain (BF) have recently been demonstrated to play a key role in controlling wakefulness. It was hypothesized that BF GABAergic neurons may participate in the regulation of general anesthesia. Here, using in vivo fiber photometry, we found that the activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia, having obviously decreased during the induction of anesthesia and being gradually restored during the emergence from anesthesia, in Vgat-Cre mice of both sexes. Activation of BF GABAergic neurons with chemogenetic and optogenetic approaches decreased sensitivity to isoflurane, delayed induction, and accelerated emergence from isoflurane anesthesia. Optogenetic activation of BF GABAergic neurons decreased EEG δ power and the burst suppression ratio (BSR) during 0.8% and 1.4% isoflurane anesthesia, respectively. Similar to the effects of activating BF GABAergic cell bodies, photostimulation of BF GABAergic terminals in the thalamic reticular nucleus (TRN) also strongly promoted cortical activation and behavioral emergence from isoflurane anesthesia. Collectively, these results showed that the GABAergic BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthesia via the GABAergic BF-TRN pathway. Our findings may provide a new target for attenuating the depth of anesthesia and accelerating emergence from general anesthesia.SIGNIFICANCE STATEMENT The basal forebrain (BF) is a key brain region controlling sleep-wake behavior. Activation of GABAergic neurons in the BF potently promotes behavioral arousal and cortical activity. Recently, many sleep-wake-related brain structures have been reported to participate in the regulation of general anesthesia. However, it is still unclear what role BF GABAergic neurons play in general anesthesia. In this study, we aim to reveal the role of BF GABAergic neurons in behavioral and cortical emergence from isoflurane anesthesia and elucidate the underlying neural pathways. Understanding the specific role of BF GABAergic neurons in isoflurane anesthesia would improve our understanding of the mechanisms of general anesthesia and may provide a new strategy for accelerating emergence from general anesthesia.


Assuntos
Prosencéfalo Basal , Isoflurano , Masculino , Feminino , Camundongos , Animais , Isoflurano/farmacologia , Prosencéfalo Basal/fisiologia , Neurônios GABAérgicos/fisiologia , Sono/fisiologia , Eletroencefalografia , Anestesia Geral
2.
Nanotechnology ; 29(36): 365601, 2018 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-29889044

RESUMO

Magnetic nanoparticles (NPs) are emerging as promising candidates for the next generation of image contrast agents and their performance is largely dependent on physicochemical properties. In this paper, a new type of 'top-down' fabrication technique was developed to synthesize ultrasmall magnetic NPs as a contrast enhancer. In a detailed, home-made oxygen plasma generator, fragments of larger KMnF3 NPs (22 nm) were broken down into smaller (<5 nm) particles with enhanced hydrophilicity. As massive activated oxygen species were produced during the process, the plasma was able to severely etch the NPs, and vacuum UV light irradiated them heavily as well, leaving them with weak crystallinity, splitting them into ultrafine particles. Also their surface transformed from hydrophobic to hydrophilic by oxidizing the passivated ligand, evidenced by the spectroscopy and microscopy results. The fragmented NPs are characteristic of unprecedented high longitudinal relaxivity (r1 = 35.52 mM-1.s-1) and appropriate biocompatibility. In a healthy mouse, the ultrafine NPs did not exert observable toxicity, this was evaluated by histology of the main organs and hemogram analysis, including kidney and liver function analysis. More interestingly, the ultrasmall NPs had a very long circulation time, as its blood half-life was around 20 h. When applied as a contrast enhancer for MRI of the patient-derived tumor xenograft model, the accumulation of KMnF3 NPs within the tumor had an average of 12.13% ID per gram, which greatly shortened the relaxation time of the tumor. Therefore the control-to-noise ratio was significantly enhanced, relative to the same dosage of Gadopentetetic acid (Magvenist) (P < 0.001). Our primary results demonstrate that fragmentation of the NPs via our home-made oxygen plasma technique might be an effective route for fabricating ultrasmall NPs, and benefit their contrast effect when applied as MRI enhancers for clinical diagnosis of tumors.


Assuntos
Meios de Contraste/química , Imageamento por Ressonância Magnética/métodos , Nanopartículas/química , Oxigênio/química , Gases em Plasma/química , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Sobrevivência Celular/efeitos dos fármacos , Meia-Vida , Humanos , Cinética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Células RAW 264.7
3.
Arterioscler Thromb Vasc Biol ; 36(11): 2176-2190, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27634835

RESUMO

OBJECTIVE: Oxidative stress plays a critical role in the development of abdominal aortic aneurysm (AAA). Intermedin (IMD) is a regulator of oxidative stress. Here, we investigated whether IMD reduces AAA by inhibiting oxidative stress. APPROACH AND RESULTS: In angiotensin II-induced ApoE-/- mouse and CaCl2-induced C57BL/6J mouse model of AAA, IMD1-53 significantly reduced the incidence of AAA and maximal aortic diameter. Ultrasonography, hematoxylin, and eosin staining and Verhoeff-van Gieson staining showed that IMD1-53 significantly decreased the enlarged aortas and elastic lamina degradation induced by angiotensin II or CaCl2. Mechanistically, IMD1-53 attenuated oxidative stress, inflammation, vascular smooth muscle cell apoptosis, and matrix metalloproteinase activation. IMD1-53 inhibited the activation of redox-sensitive signaling pathways, decreased the mRNA and protein expression of nicotinamide adenine dinucleotide phosphate oxidase subunits, and reduced the activity of nicotinamide adenine dinucleotide phosphate oxidase in AAA mice. Expression of Nox4 was upregulated in human AAA segments and in angiotensin II-treated mouse aortas and was markedly decreased by IMD1-53. In vitro, vascular smooth muscle cells with small-interfering RNA knockdown of IMD showed significantly increased angiotensin II-induced reactive oxygen species, and small-interfering RNA knockdown of Nox4 markedly inhibited the reactive oxygen species. IMD knockdown further increased the apoptosis of vascular smooth muscle cells and inflammation, which was reversed by Nox4 knockdown. Preincubation with IMD17-47 and protein kinase A inhibitor H89 inhibited the effect of IMD1-53, reducing Nox4 protein levels. CONCLUSIONS: IMD1-53 could have a protective effect on AAA by inhibiting oxidative stress.


Assuntos
Antioxidantes/farmacologia , Aorta Abdominal/efeitos dos fármacos , Aneurisma da Aorta Abdominal/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Hormônios Peptídicos/farmacologia , Adrenomedulina/metabolismo , Angiotensina II , Animais , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/patologia , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Apoptose/efeitos dos fármacos , Cloreto de Cálcio , Células Cultivadas , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Dilatação Patológica , Modelos Animais de Doenças , Genótipo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , NADPH Oxidases/metabolismo , Neuropeptídeos/metabolismo , Hormônios Peptídicos/metabolismo , Fenótipo , Interferência de RNA , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Transfecção
4.
Kidney Int ; 89(3): 586-600, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26880455

RESUMO

Deficiency in α-Klotho is involved in the pathogenesis of vascular calcification. Since intermedin (IMD)1-53 (a calcitonin/calcitonin gene-related peptide) protects against vascular calcification, we studied whether IMD1-53 inhibits vascular calcification by upregulating α-Klotho. A rat model of chronic kidney disease (CKD) with vascular calcification induced by the 5/6 nephrectomy plus vitamin D3 was used for study. The aortas of rats with CKD showed reduced IMD content but an increase of its receptor, calcitonin receptor-like receptor, and its receptor modifier, receptor activity-modifying protein 3. IMD1-53 treatment reduced vascular calcification. The expression of α-Klotho was greatly decreased in the aortas of rats with CKD but increased in the aortas of IMD1-53-treated rats with CKD. In vitro, IMD1-53 increased α-Klotho protein level in calcified vascular smooth muscle cells. α-Klotho knockdown blocked the inhibitory effect of IMD1-53 on vascular smooth muscle cell calcification and their transformation into osteoblast-like cells. The effect of IMD1-53 to upregulate α-Klotho and inhibit vascular smooth muscle cell calcification was abolished by knockdown of its receptor or its modifier protein, or treatment with the protein kinase A inhibitor H89. Thus, IMD1-53 may attenuate vascular calcification by upregulating α-Klotho via the calcitonin receptor/modifying protein complex and protein kinase A signaling.


Assuntos
Transdiferenciação Celular/efeitos dos fármacos , Glucuronidase/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Hormônios Peptídicos/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Calcificação Vascular/prevenção & controle , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Células Cultivadas , Colecalciferol , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Modelos Animais de Doenças , Glucuronidase/genética , Humanos , Proteínas Klotho , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Nefrectomia , Osteoblastos/metabolismo , Osteoblastos/patologia , Fenótipo , Interferência de RNA , Ratos Sprague-Dawley , Proteína 3 Modificadora da Atividade de Receptores/metabolismo , Receptores da Calcitonina/metabolismo , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Transdução de Sinais/efeitos dos fármacos , Transfecção , Regulação para Cima , Calcificação Vascular/genética , Calcificação Vascular/metabolismo , Calcificação Vascular/patologia
5.
Opt Express ; 23(25): 31864-73, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26698978

RESUMO

The unconditional stable finite-difference time-domain (FDTD) method based on field expansion with weighted Laguerre polynomials (WLPs) is applied to model electromagnetic wave propagation in gyrotropic materials. The conventional Yee cell is modified to have the tightly coupled current density components located at the same spatial position. The perfectly matched layer (PML) is formulated in a stretched-coordinate (SC) system with the complex-frequency-shifted (CFS) factor to achieve good absorption performance. Numerical examples are shown to validate the accuracy and efficiency of the proposed method.

6.
Heart Vessels ; 30(5): 657-68, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25092223

RESUMO

Fibroblast growth factor 21 (FGF-21) is an endocrine factor that can be secreted into circulation by the liver. FGF-21 takes part in metabolic actions and is thought to be a promising candidate for the treatment of diabetes. However, the role of FGF-21 in atherosclerosis is unknown. In this study, apoE(-/-) mice were fed an atherogenic diet for 4 weeks with and without subcutaneous injections of FGF-21. ApoE(-/-) mice fed an atherogenic diet showed hyperlipidemia, a large plaque area in aortas and increased vessel wall thickness. Plasma FGF-21 content and protein level of FGF receptor 1 (FGFR1) in aortas was greater in apoE(-/-) than C57BL/6J mice. Exogenous FGF-21 treatment significantly ameliorated dyslipidemia in apoE(-/-) mice. FGF-21-treated apoE(-/-) mice showed reduced number of aortic plaques and plaque area as well as reduced number of TUNEL-positive cells. Protein levels of the endoplasmic reticulum stress markers glucose-regulated protein 94, caspase-12 and C/EBP homologous protein were reduced by 34.5, 31.4 and 26.5 %, respectively, in apoE(-/-) mice. Endogenous expression of FGF-21 and its receptor FGFR1 were upregulated in apoE(-/-) mice, and exogenous administration of FGF-21 ameliorated the atherogenic-induced dyslipidemia and vascular atherosclerotic lesions. FGF-21 protecting against atherosclerosis might be in part by its inhibitory effects on endoplasmic reticulum stress-mediated apoptosis.


Assuntos
Apolipoproteínas E/deficiência , Apoptose , Aterosclerose/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/biossíntese , Animais , Apolipoproteínas E/sangue , Aterosclerose/etiologia , Aterosclerose/patologia , Western Blotting , Modelos Animais de Doenças , Dislipidemias/complicações , Dislipidemias/metabolismo , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/uso terapêutico , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Radioimunoensaio
7.
Exp Parasitol ; 145: 1-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24996067

RESUMO

Gastrointestinal helminth infection, including Trichinella spiralis, initiates a series of intestinal structural, cellular and physiological changes. Intestinal invasion is an important stage of trichinellosis because it determines the development and subsequent course of the disease and its consequences. Apoptosis mediated by endoplasmic reticulum stress (ERS) plays a key role in infectious diseases, but the effect of T. spiralis infection on inducing apoptosis in the small intestine has been neglected. We investigated apoptosis and changes in ERS-associated apoptosis molecules in the intestine of mice with T. spiralis infection. TUNEL staining and detection of the apoptotic marker cleaved caspase 3 revealed that apoptosis occurred in the mouse intestine at days 3 and 7 post-infection. The ER chaperone 78-kDa glucose-regulated protein (GRP78) was upregulated at days 3 and 7 post-infection. The ERS-associated apoptosis molecules C/EBP homologous protein, cleaved caspase 12 and c-Jun NH2-terminal kinase were upregulated at days 3 and 7, days 3, 7 and 10 and days 7 and 10 post-infection, respectively. Thus, apoptosis occurred in the intestine of mice with T. spiralis infection, and the ERS-mediated apoptosis pathway was activated by infection with this small intestine dwelling nematode.


Assuntos
Apoptose , Estresse do Retículo Endoplasmático/fisiologia , Jejuno/patologia , Trichinella spiralis/fisiologia , Triquinelose/patologia , Animais , Caspase 12/metabolismo , Chaperona BiP do Retículo Endoplasmático , Feminino , Proteínas de Choque Térmico/metabolismo , Jejuno/parasitologia , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , Camundongos Endogâmicos ICR , Coelhos , Fator de Transcrição CHOP/metabolismo , Regulação para Cima
8.
Zhongguo Zhong Yao Za Zhi ; 39(12): 2341-4, 2014 Jun.
Artigo em Zh | MEDLINE | ID: mdl-25244772

RESUMO

OBJECTIVE: To investigate the mechanism that the formulas for activating blood and resolving stasis can regulate hemopoietic stem cell to produce new blood. METHOD: Rats were established animal model of acute cerebral infarction by referencing Olivette' method. They were randomly divided into model group, the group of the high, middle, low dose of the formulas for activating blood and resolving stasis. Each group and then wasrandomly divided into subgroups by 1, 3, 7, 14, 28 d. Xuesaitong capsule was formulated into 20, 40, 60 g x L(-1) with normal saline. The rats were given gavage drugs once a day until the experient ended, and the model group was administrated by intragastrical perfusion of normal saline. ELISA was used to detect the expression of SCF in peripheral blood and bone marrow among different groups at different time points. Flow cytometry was used to observe the changes of CD117 in blood and bone marrow. RESULT: The CD117+ HSC and SCF concentration in peripheral blood and bone marrow of model group were increasing during 1-14 d,there was a peak on the 14th day, then the expression was reducing. CD117+ HSC and SCF concentration rising trend in the group of the high, middle dose of the formulas for activating blood and resolving stasis was preceded model group (P < 0.05). CONCLUSION: Activating blood and resolving stasis can regulate hemopoietic stem cell to produce new blood, and it is through the regulation of CD117+ HSC number to achieve the purpose.


Assuntos
Infarto Cerebral/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Células-Tronco Hematopoéticas/efeitos dos fármacos , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Cápsulas , Infarto Cerebral/sangue , Infarto Cerebral/genética , Infarto Cerebral/metabolismo , Química Farmacêutica , Células-Tronco Hematopoéticas/metabolismo , Humanos , Masculino , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Células-Tronco/genética , Fator de Células-Tronco/metabolismo
9.
Parasitol Res ; 112(10): 3457-63, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23832642

RESUMO

The parasitic nematode Trichinella spiralis can cause trichinellosis, which leads to pathological processes in the intestine and muscle. The intestinal invasion determines the development, subsequent course, and consequences of the disease. Gastrointestinal nematode infection, including with T. spiralis, is accompanied by a rapid and reversible expansion of mucosal mast cell and goblet cell in the intestinal epithelium, which play important roles in the host immune response to parasite and worm expulsion from the intestine. Taurine and its derivatives have anti-infection and anti-inflammatory properties. We investigated whether taurine supplementation in mice could influence the development and pathological processes of infection with T. spiralis. Supplementing 1% taurine in drinking water in mice infected with T. spiralis could alleviate the burden of intestinal adult worms on days 7 and 10 postinfection (all p < 0.01) and the formation of infective muscle larvae in striated muscle during T. spiralis infection (p < 0.01). As compared with T. spiralis infection alone, taurine treatment increased the number of goblet cells on days 7, 10, and 15 (p < 0.01 and p < 0.05) and alleviated intestinal mucosal mast cell hyperplasia on days 10 and 15 (all p < 0.01). So taurine supplementation in drinking water increased infection-induced intestinal goblet cell hyperplasia and ameliorated mucosal mastocytosis. Thus, taurine can ameliorate the pathological processes of trichinellosis and may be of great value for the treatment and prevention of infection with T. spiralis and other gastrointestinal nematodes.


Assuntos
Água Potável/química , Enteropatias Parasitárias/tratamento farmacológico , Taurina/farmacologia , Triquinelose/tratamento farmacológico , Animais , Feminino , Enteropatias Parasitárias/parasitologia , Intestinos/citologia , Intestinos/patologia , Mastócitos/citologia , Mastócitos/patologia , Mastocitose/tratamento farmacológico , Camundongos , Camundongos Endogâmicos ICR , Músculo Esquelético/parasitologia , Taurina/administração & dosagem , Taurina/química , Trichinella spiralis , Triquinelose/parasitologia
10.
Clin Ther ; 45(10): 991-1003, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37690913

RESUMO

PURPOSE: Viral myocarditis (VMC) is a life-threatening disease that can affect all ages and genders, with middle-aged adults being particularly susceptible. Numerous systematic reviews have been conducted to investigate the efficacy and safety of Chinese herbal medicine (CHM) in treating adult viral myocarditis (AVM). The objective of this study was to conduct a comprehensive overview of systematic reviews and meta-analyses of randomized controlled trials (RCTs) regarding the efficacy and safety of CHM for AVM. METHODS: A comprehensive systematic search was conducted across 8 electronic databases from their inception to June 23, 2022, augmented by manual searches of the gray literature. Systematic reviews were independently selected and data extracted in accordance with predetermined criteria by 2 reviewers. Included systematic reviews were assessed for methodologic and reporting quality using Assessing the Methodological Quality of Systematic Reviews 2 and Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The quality of evidence relating to outcome measures was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation tool. Recalculation of effect sizes and subsequent determination of 95% CIs were conducted with either a fixed-effects or random-effects model. FINDINGS: The current overview of systematic reviews included a total of 6 systematic reviews, which reported on 67 RCTs with a participant pool of 5611 individuals. The findings of our study indicate that the combination of CHM and Western medications had positive effects on the effective rate, cure rate, ECG recovery, atrial premature contraction/premature ventricular contraction, left ventricular ejection fraction, myocardial enzymes, and improvement of clinical symptoms for AVM. The adverse drug reactions in the combination therapy group were generally less than or lighter than that in the Western medication group (relative risk = 0.79; 95% CI, 0.44-1.40; P > 0.05, I2 = 0). IMPLICATIONS: Our research results provide evidence that combining CHM with Western medicine could offer potential benefits for patients with AVM. However, the number of studies included in our review is limited and the methodologic quality of these studies is modest. Therefore, there are potential uncertainties regarding the conclusion that CHM with Western medication may benefit patients with AVM. We call for more large-scale, high-quality studies with standardized designs to further verify and support our findings. This would promote a better understanding of the efficacy and safety profile of CHM and provide reliable reference evidence for clinical practice and policy making. Moreover, future research should explore optimal drug combinations, examine therapeutic doses and durations of CHM combination therapy, and evaluate its long-term efficacy and safety.


Assuntos
Medicamentos de Ervas Chinesas , Miocardite , Adulto , Humanos , Pessoa de Meia-Idade , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/efeitos adversos , Miocardite/tratamento farmacológico , Miocardite/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Metanálise como Assunto
11.
Curr Med Sci ; 42(5): 966-973, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35788946

RESUMO

OBJECTIVE: Restoring the blood perfusion of ischemic heart tissues is the main treatment for myocardial ischemia. However, the accompanying myocardial ischemia reperfusion injury (IRI) would aggravate myocardial damage. Previous studies have confirmed that aryl hydrocarbon receptor (AhR) is closely correlated to kidney and intestinal IRI. The present study aimed to explore the relationship between AhR and myocardial IRI. METHODS: An oxygen glucose deprivation/reoxygenation (OGD/R) model of H9c2 cells and an ischemia/reperfusion (I/R) model of Sprague-Dawley rat myocardium were established. OGD/R cells and myocardial IRI rats were treated with different concentrations of the AhR antagonist CH-223191 or agonist 6-formylindolo[3,2-b] carbazole (FICZ). Under the conditions of normoxia and hypoxia/reoxygenation, the activity of cardiomyocytes, lactate dehydrogenase (LDH) and cell reactive oxygen species (ROS) were detected. In rats, myocardial pathological damage and markers of myocardial injury were detected. RESULTS: According to the results of the cell viability, LDH and ROS tests in vitro, both CH-223191 and FICZ showed no myocardial protection under OGD/R conditions. However, the histological staining and analysis of myocardial injury marker LDH in vitro revealed that CH-223191 could significantly reduce the myocardial IRI. CONCLUSION: AhR exhibited a different effect on myocardial IRI in vitro and in vivo. In vivo, CH-223191 could significantly alleviate the myocardial IRI, suggesting that inhibition of AhR may play a role in myocardial protection, and AhR may serve as a potential treatment target for myocardial IRI.


Assuntos
Traumatismo por Reperfusão Miocárdica , Ratos , Animais , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Espécies Reativas de Oxigênio , Receptores de Hidrocarboneto Arílico/genética , Ratos Sprague-Dawley , Apoptose , Miócitos Cardíacos , Glucose , Oxigênio , Carbazóis/farmacologia , Lactato Desidrogenases
12.
Inflammation ; 45(4): 1568-1584, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35175495

RESUMO

Intermedin (IMD), a paracrine/autocrine peptide, protects against cardiac fibrosis. However, the underlying mechanism remains poorly understood. Previous study reports that activation of nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome contributes to cardiac fibrosis. In this study, we aimed to investigate whether IMD mitigated cardiac fibrosis by inhibiting NLRP3. Cardiac fibrosis was induced by angiotensin II (Ang II) infusion for 2 weeks in rats. Western blot, real-time PCR, histological staining, immunofluorescence assay, RNA sequencing, echocardiography, and hemodynamics were used to detect the role and the mechanism of IMD in cardiac fibrosis. Ang II infusion resulted in rat cardiac fibrosis, shown as over-deposition of myocardial interstitial collagen and cardiac dysfunction. Importantly, NLRP3 activation and endoplasmic reticulum stress (ERS) were found in Ang II-treated rat myocardium. Ang II infusion decreased the expression of IMD and increased the expression of the receptor system of IMD in the fibrotic rat myocardium. IMD treatment attenuated the cardiac fibrosis and improved cardiac function. In addition, IMD inhibited the upregulation of NLRP3 markers and ERS markers induced by Ang II. In vitro, IMD knockdown by small interfering RNA significantly promoted the Ang II-induced cardiac fibroblast and NLRP3 activation. Moreover, silencing of inositol requiring enzyme 1 α (IRE1α) blocked the effects of IMD inhibiting fibroblast and NLRP3 activation. Pre-incubation with PKA pathway inhibitor H89 blocked the effects of IMD on the anti-ERS, anti-NLRP3, and anti-fibrotic response. In conclusion, IMD alleviated cardiac fibrosis by inhibiting NLRP3 inflammasome activation through suppressing IRE1α via the cAMP/PKA pathway.


Assuntos
Adrenomedulina , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Neuropeptídeos , Adrenomedulina/genética , Adrenomedulina/metabolismo , Angiotensina II/farmacologia , Animais , Células Cultivadas , Endorribonucleases , Fibrose , Inflamassomos/metabolismo , Complexos Multienzimáticos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Proteínas Serina-Treonina Quinases , Ratos
13.
Biochem Biophys Res Commun ; 413(2): 342-7, 2011 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-21893044

RESUMO

Hydrogen sulphide (H(2)S) has been shown to play a crucial role in cardiovascular physiology and disease. However, there is no information about the possible role of H(2)S in cardiomyocyte hypertrophy (CH). Our results showed that pretreatment with NaHS, an H(2)S donor, significantly reduced [(3)H]-leucine incorporation, cell surface area, mRNA expression of brain natriuretic peptide (BNP), intracellular reactive oxygen species (ROS), miR-21 and increased atrial natriuretic peptide (ANP) and miR-133a expression in hypertrophic cardiomyocytes. Anti-miR133a inhibitor transfection partly reduced the anti-hypertrophic effect of NaHS. In conclusion, H(2)S is a direct inhibitor of CH; it acts by increasing miR-133a and inhibiting the increase in intracellular ROS.


Assuntos
Cardiomegalia/metabolismo , Cardiomegalia/patologia , Sulfeto de Hidrogênio/metabolismo , MicroRNAs/biossíntese , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Animais , Linhagem Celular , Hipertrofia/metabolismo , Hipertrofia/patologia , MicroRNAs/genética , Miócitos Cardíacos/efeitos dos fármacos , Peptídeo Natriurético Encefálico/biossíntese , Peptídeo Natriurético Encefálico/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Espécies Reativas de Oxigênio/metabolismo , Sulfetos/farmacologia , Regulação para Cima
14.
J Tradit Chin Med ; 31(3): 203-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21977864

RESUMO

OBJECTIVE: To investigate the effects of panax notoginseng saponins (PNS) on homing of C-kit+ bone mesenchymal stem cells (BMSCs) to the infarction heart. METHODS: The acute myocardial infraction (AMI) model was established in 140 Wistar rats, 105 model rats survived after operation, and the model rats were randomly divided into five groups, 21 rats in each group: Western medicine group mobilized by subcutaneous injection of human granuloctye colony stimulating factor (G-CSF) 50 microg x kg(-1) x d(-1); sham operation group and a model group treated by subcutaneous injection of normal saline 50 microg x kg(-1) x d(-1); Chinese medicine group mobilized by intraperitoneal injection of Xuesaitong (see text) (ingredients of PNS) 150 mg x kg(-1) x d(-1); integrative medicine group mobilized by subcutaneous injection of G-CSF 50 microg x kg(-1) x d(-1) and intraperitoneal injection of Xuesaitong 150 mg x kg(-1) x d(-1). Except for the sham-operated group, each group was divided into three sub-groups by three time points of 1 d, 7 d and 14 d. G-CSF was injected once a day for 7 d. Xuesaitong was injected once a day until the rats were killed. The flow cytometry was used for detection of C-kit+ cells in the peripheral blood in different time points, and immunohistochemical method was used for detection of the changes of C-kit+ cell and Ki-67+ cell numbers in the marginal zone of AMI. RESULTS: Twenty-four hours after the operation, C-kit+ cells had a slight increase in the model group compared with the sham operation group (P > 0.05). The peripheral blood C-kit+ cells in the integrative group increased significantly compared with the other groups on 7 d and 14 d (all P < 0.05). Meanwhile the expression of C-kit+ cells and Ki-67+ cells in the marginal zone of AMI in the integrative group increased significantly compared with the Chinese medicine group, the western medicine group and the model group on 1 d, 7 d and 14 d (all P < 0.05), and the cells in the integrative group decreased significantly on 14 d compared with that on 7 d (P < 0.05). CONCLUSION: PNS can cooperate with G-CSF to mobilize C-kit+ BMSCs from the marrow into the peripheral blood and promote them "homing" to the infarction heart.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Panax notoginseng/química , Proteínas Proto-Oncogênicas c-kit/metabolismo , Saponinas/uso terapêutico , Animais , Feminino , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Infarto do Miocárdio/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar
15.
Biomed Res Int ; 2021: 6614812, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33928150

RESUMO

INTRODUCTION: High mortality associated with carbapenemase-producing Gram-negative bacteria (CP-GNB) has evolved into a global health threat. Rapid and accurate detection as well as prompt treatment are of great significance in this case. Xpert Carba-R, a multiple qualitative analysis designed to detect five clinically relevant carbapenem-resistant gene families within one hour, is regarded as reliable, accurate, and easy-to-operate. This study is to present a systematic evaluation of the performance of Xpert Carba-R in detecting carbapenemase genes in GNB suspected for carbapenemase production. METHODS: We searched and screened the literature on "Xpert Carba-R" in the database of PubMed, Web of Science, Embase, and Cochrane Library, employing two independent evaluators to collect data, respectively. Then, statistical analysis of the data obtained was performed by the Stata 12.0 software to measure the accuracy of Xpert Carba-R assay in detecting the carbapenemase genes in GNB. RESULTS: We screened a total of 1767 Gram-negative bacillus isolates documented in 9 articles. The precision of the detection of OXA-48 carbapenemase genes was 100%; that of NDM = 100%; that of VIM = 100%. When it came to KPC, the precision rate was 100%; that of IMP = 99%. The overall accuracy of the detection of carbapenemase genes was 100%. CONCLUSIONS: Xpert Carba-R assay demonstrates a 100% precision in identifying carbapenemase genes in GNB. It can be seen that Xpert Carba-R method is an effective tool for early clinical detection, which is suitable for the detection of carbapenase gene in GNB.


Assuntos
Proteínas de Bactérias/genética , Ensaios Enzimáticos/métodos , Bactérias Gram-Negativas/enzimologia , Bactérias Gram-Negativas/genética , beta-Lactamases/genética , Bactérias Gram-Negativas/isolamento & purificação , Humanos , Viés de Publicação , Especificidade da Espécie
16.
Huan Jing Ke Xue ; 41(10): 4455-4461, 2020 Oct 08.
Artigo em Zh | MEDLINE | ID: mdl-33124377

RESUMO

As flue gas desulfurization (FGD) was one of the most important purification processes of coal-fired boilers, we selected four boilers, which were equipped with wet limestone, furnace calcium injection, ammonia-based, and double-alkali FGDs, to research the influence of FGDs on the flue particulate matter (PM). The flue PM before and after the FGD were sampled using laboratory resuspension and dilution tunnel sampling methods, respectively, and the PM was analyzed for its chemical composition (i.e., ions, elements, and carbon). The results showed that the types of desulfurizers could influence the composition of the flue PM. After passing through the wet limestone, ammonia-based, and double-alkali FGDs, the proportion of Ca, NH4+, and Na in PM2.5 increased from 5.1% to 24.8%, from 0.8% to 7.3%, and from 0.9% to 1.7%, respectively. The influence of wet and dry FGDs on the flue PM were different. The fraction of ions in the PM emitted from the wet FGD were higher than those from the dry FGD. The proportion of SO42- in the flue PM2.5 increased from 2.0% and 6.7% to 9.6% and 11.9% using the wet limestone and ammonia-based FGDs, respectively, and Cl- increased from 0.4% and 1.2% to 3.8% and 5.2%. In addition, the amount of heavy metals (e.g., Cr, Pb, Cu, Ti, and Mn) in PM2.5 declined after the wet FGDs. The PM2.5 emitted from the dry FGD boiler was richer in crustal elements, such as Al, Si, and Fe, than that from the wet FGDs. The wet FGDs also effected the carbonaceous components of the flue PM. After passing through the wet limestone and ammonia-based FGDs, the proportion of elemental carbon in the flue PM2.5 decreased from 6.1% to 0.9% and from 3.6% to 0.7% respectively, but the organic carbon content did not decrease.

17.
Zhonghua Gan Zang Bing Za Zhi ; 17(12): 921-4, 2009 Dec.
Artigo em Zh | MEDLINE | ID: mdl-20038334

RESUMO

OBJECTIVE: To profile the protein expression in activated rat hepatic stellate cells (HSCs). METHODS: Primary rat HSCs were isolated and cultured in vitro. After 10 days in vitro culture, the HSCs were activated. Total protein extracted from these activated HSCs were digested, and the obtained peptides were analyzed by using online 2D nanoLC-MS/MS. The identified proteins were classified according to their distributions and functions. RESULTS: 1014 proteins were identified from 50 microg HSCs protein extract, the molecular weights of these proteins ranged from 7832 Da to 588,364 Da. Most of these proteins resided in nucleus, cytoskeleton, mitochondrion and endoplasmic reticulum. And these proteins were mainly involved in nucleic acid metabolism, organelle organization, signal transduction and energy generation. Among these proteins, alpha-smooth muscle actin, vimentin and desmin were specifically expressed in activated HSCs. CONCLUSION: To the best of our knowledge, this is the most comprehensive protein expression profile of activated rat HSCs.


Assuntos
Actinas/análise , Cromatografia Líquida de Alta Pressão/métodos , Células Estreladas do Fígado/metabolismo , Proteoma/análise , Vimentina/análise , Actinas/metabolismo , Animais , Núcleo Celular/metabolismo , Células Cultivadas , Desmina/análise , Desmina/metabolismo , Masculino , Proteoma/metabolismo , Proteômica , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Vimentina/metabolismo
18.
Huan Jing Ke Xue ; 40(6): 2533-2539, 2019 Jun 08.
Artigo em Zh | MEDLINE | ID: mdl-31854643

RESUMO

There are few analyses on the components of particulate matter emitted from waste incineration plants. In past studies, analyses of particle size distribution characteristics of the components were mainly targeted at particles with larger particle sizes. An electrical low pressure impactor (ELPI) was used in this study to collect the particulate matter emitted from a waste incineration plant, and the elements and carbonaceous components of these samples were analyzed. The particle size characteristics of organic carbon (OC), elemental carbon (EC), and heavy metal elements in 14 particle size segments were analyzed and composition profiles of elements and carbonaceous components of PM1, PM2.5, and PM10 from the waste incineration plant were established to provide a reference for refined source apportionment research. The results showed that the main components of the waste incineration plant included Al, Si, S, Ca, Cr, Fe, OC, EC, etc. OC and Ca were dominating components, and mass fractions of these components in the PM2.5 profile were 10.15% and 12.37%, respectively. The contents of heavy metals were ranked as Cr > Pb > Zn > Mn > Cu > Cd > Ni, and the mass fractions of Cr and Pb in PM2.5 amounted to 1.83% and 0.74%, respectively. OC in the range of 2.39-3.99 and 6.68-9.91 µm accounted for 15.02% and 20.45% of the total OC content, respectively, and the content of OC in fine particles was higher than that in coarse particles. The content of EC in fine particles was much higher than that in coarse particles, and it accounted for 14.8% in the 0.382-0.613 µm particle size. Heavy metal elements such as Cr, Mn, Ni, Cu, Zn, Cd, and Pb were mainly concentrated in the fine particles.

19.
Yi Chuan ; 30(5): 583-9, 2008 May.
Artigo em Zh | MEDLINE | ID: mdl-18487147

RESUMO

To investigate the genetic polymorphisms of 11 Y-chromosomal short tandem repeats(STR) loci in Manchu population, and to evaluate their forensic application values and genetic relationships with 16 other populations of China, 11 Y-STR loci in 203 unrelated Manchu individuals in Liaoning were amplified with PowerPlex Y System, and the PCR products were analyzed by 310 Genetic Analyzer. Cluster analysis and phylogenic trees were applied to show the genetic distance among the populations. As a result, a total of 189 haplotypes were identified and the overall haplotypes diversity for the 11 Y-STR loci was 0.9991. The gene diversity values (GD) for each locus ranged from 0.4594 (DYS391) to 0.9258 (DYS385a/b). Comparing with 16 populations, genetic distance between Manchu and Northeast Han population was the smallest(0.0015), while genetic distance between Man and Uygur ethnic the largest(0.1485). The phylogenetic tree was similar to the results of clustering analysis. The genetic distribution of 11 Y-STR loci in Liaoning Manchu population showed favorable polymorphisms, and was thus suitable for forensic identification and paternity testing in local area. The study of genetic diversity among different populations is useful for the research of their origins, migrations and their relationships.


Assuntos
Cromossomos Humanos Y/genética , Polimorfismo Genético/genética , Sequências de Repetição em Tandem/genética , China , Haplótipos , Humanos , Masculino , Reação em Cadeia da Polimerase
20.
Zhongguo Zhong Yao Za Zhi ; 33(16): 2037-40, 2008 Aug.
Artigo em Zh | MEDLINE | ID: mdl-19086649

RESUMO

OBJECTIVE: To study the anti-depressive mechanism of Shugan Jiannao Tiaoyu tablets (SJTT) and provide evidence for clinical application. METHOD: Evaluate the behavioral index changes of rat model through the methods of motionless-time of swimming by force, and the consumption of sucrose, etc, meanwhile, use transmission electron microscope (TEM) to observe the cell ultrastructure and study the influence of the hypothalamic corticotrophin releasing hormone (HCRH) gene expression with the RT-PCR technique. RESULT: SJTI could reduce the hippocampal neuronal damage caused by stress, protect the brain injury of the depressive rats. SJTT could down-regulate model rats' HCRH. Compared with the model group (P < 0.05), which indicates that SJTT could inhibit the hyperfunction of HPA Axis by down-regulating model rats' HCRH, to achieve the antidepressant effect.


Assuntos
Hormônio Liberador da Corticotropina/genética , Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Animais , Depressão/patologia , Modelos Animais de Doenças , Hipotálamo/ultraestrutura , Masculino , Microscopia Eletrônica de Transmissão , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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