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2.
ACS Nano ; 17(9): 8074-8082, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37122036

RESUMO

Conjugated polymer chains in compact conformations or in films exhibit spectral features that can be attributed to interactions between individual conjugated segments of the chain, including formation of aggregates or excimers. Here, we use atomic force microscopy (AFM) on single chains of the conjugated polymer polyfluorene (PFO) to control the intersegment interactions by mechanically unfolding the chain. Simultaneously with the force spectroscopy we monitor fluorescence from the single PFO chains using a fluorescence microscope. We found that mechanical stretching of the chain causes disappearance of the green emission band. This observation provides evidence that the green emission originates from an intrachain aggregated state on the self-folded chain, which is decoupled by the stretching. In addition, the stretching upon laser irradiation leads to the appearance of additional features in the force spectra, small force peaks in the initial stages of the unfolding. These features are attributed to a combination of excitonic and van der Waals coupling of a ground-state intrachain aggregate.

3.
Acupunct Med ; 41(1): 3-15, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35579024

RESUMO

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by dysregulation of the host response to infection. Acupuncture is used for treatment of inflammatory diseases; however, its effectiveness and safety as a complementary therapy for sepsis has not been fully explored. METHODS: Data were retrieved from eight databases. Randomized controlled trials (RCTs) that compared acupuncture plus conventional therapies versus conventional therapies alone were included. Pre-specified primary outcomes were mortality at 28 days and Acute Physiologic and Chronic Health Evaluation (APACHE) II scores. RESULTS: A total of 17 studies with 1099 participants were included in this study. In terms of the primary outcomes, acupuncture plus routine therapy reduced mortality at 28 days (risk ratio (RR)): 0.69, 95% confidence interval (CI): 0.52 to 0.91, p < 0.001) and APACHE II scores (mean difference (MD): -2.84, 95% CI: -4.09 to -1.58, p < 0.001) at day 7 after treatment compared with routine therapy alone. In terms of secondary outcomes, acupuncture plus routine therapy reduced white blood cell counts and levels of procalcitonin (PCT), tumor necrosis factor (TNF)-α, interleukin (IL)-6 and lactic acid and intra-abdominal pressure (IAP), and improved CD3+, CD4+ and monocytes of human leukocyte antigen (HLA)-DR at day 7 after treatment compared with routine therapy alone. However, acupuncture plus routine therapy had no significant effects on levels of IL-10, C-reactive protein (CRP), CD8+ and CD4+/CD8+ ratios compared with routine therapy alone. Quality of evidence was low to very low for all parameters (GRADE). CONCLUSION: The available evidence showed that combination of acupuncture and routine therapy may have benefit for sepsis compared with use of routine therapy only. Due to the low degree of certainty regarding its effects, further research is required. TRIAL REGISTRATION NUMBER: ICRD42019141491 (PROSPERO).


Assuntos
Terapia por Acupuntura , Terapias Complementares , Sepse , Humanos , Fator de Necrose Tumoral alfa , Interleucina-6 , Sepse/terapia
4.
Science ; 377(6612): 1298-1304, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36108005

RESUMO

Taste sensing is a sophisticated chemosensory process, and bitter taste perception is mediated by type 2 taste receptors (TAS2Rs), or class T G protein-coupled receptors. Understanding the detailed molecular mechanisms behind taste sensation is hindered by a lack of experimental receptor structures. Here, we report the cryo-electron microscopy structures of human TAS2R46 complexed with chimeric mini-G protein gustducin, in both strychnine-bound and apo forms. Several features of TAS2R46 are disclosed, including distinct receptor structures that compare with known GPCRs, a new "toggle switch," activation-related motifs, and precoupling with mini-G protein gustducin. Furthermore, the dynamic extracellular and more-static intracellular parts of TAS2R46 suggest possible diverse ligand-recognition and activation processes. This study provides a basis for further exploration of other bitter taste receptors and their therapeutic applications.


Assuntos
Neurotoxinas , Receptores Acoplados a Proteínas G , Estricnina , Paladar , Microscopia Crioeletrônica , Humanos , Ligantes , Neurotoxinas/farmacologia , Conformação Proteica , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/química , Estricnina/farmacologia , Paladar/efeitos dos fármacos
5.
PLoS One ; 17(1): e0263166, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35085351

RESUMO

BACKGROUND: Patients with functional gastrointestinal disorders (FGIDs) also often have emotional symptoms, such as anxiety and depression. The main drugs used for the treatment of FGIDs mainly target single gastrointestinal symptoms and are not effective in regulating emotional symptoms. Evidence has shown that acupuncture can relieve gastrointestinal symptoms in FGIDs patients, but there is no high-quality evidence to show that acupuncture can relieve psychological symptoms in these patients. OBJECTIVES: To systematically evaluate the clinical efficacy and safety of acupuncture for emotional symptoms in patients with FGIDs. METHODS: Randomized controlled trials (RCTs) published from database inception through July 31, 2021, were retrieved from three English-language databases (PubMed, the Cochrane Central Register of Controlled Trials, and Embase) and five Chinese-language databases (the China National Knowledge Infrastructure, Wanfang, VIP, Chinese Biomedical, and TCM Literature Analysis and Retrieval databases). RCTs that compared acupuncture with sham acupuncture and pharmacotherapy were included in this study. The score on the depression or anxiety scale after treatment were considered as primary outcomes. The 'meta' package (version 4.19-0) in RStudio 1.1.463 was used to analyse the data. RESULTS: A total of 2151 patients from 24 RCTs were included in this study. Compared with sham acupuncture, acupuncture was not significantly better at relieving anxiety (standardized mean difference [SMD] -0.35, 95% CI -1.05 to 0.33) and depression (SMD -0.32, 95% CI -0.71 to 0.07) symptoms. Compared with pharmacotherapy, acupuncture was significantly better at relieving anxiety (SMD -0.64, 95% CI -0.93 to -0.35) and depression (SMD -0.46, 95% CI -0.69 to -0.22) symptoms. CONCLUSIONS: This meta-analysis found that acupuncture can alleviate emotional symptoms in FGID patients better than pharmacotherapy. However, it is not clear whether this effect is based on the placebo effect, specific effect or nonspecific effect of acupuncture. The evidence should be proven by rigorously designed RCTs in the future. PROSPERO REGISTRATION NUMBER: CRD42021271899.


Assuntos
Terapia por Acupuntura/efeitos adversos , Ansiedade/complicações , Ansiedade/terapia , Depressão/complicações , Depressão/terapia , Gastroenteropatias/complicações , Gastroenteropatias/terapia , Adolescente , Adulto , Idoso , Emoções , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
6.
Medicine (Baltimore) ; 100(49): e28174, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34889294

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease which making people difficult to breathe and often accompanied with headache. Acupuncture have been proved the therapeutic effect on headache, but there has been no high-quality evidence on acupuncture for the headache in COVID-19. This study is designed to evaluate the effectiveness and safety of acupuncture for headache in COVID-19. METHODS: Randomized controlled trials from December 2019 to July 2021 will be included without restrictions on language or publication date. PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Databases, China National Knowledge Infrastructure, Wanfang database, and VIP database will be searched. Two researchers will independently select studies, extract data and evaluate study quality. Cochrane risk of bias tool for randomized trials will be used to assess the risk of bias of included studies. Statistical analyses will be performed using the Review Manager V.5.3 and stata 14.0. ETHICS AND DISSEMINATION: This study will not involve personal information. Ethical approval will not be required. We will publish the results in a peer-reviewed journal. PROSPERO TRIAL REGISTRATION NUMBER: CRD42021270722.


Assuntos
Terapia por Acupuntura , COVID-19/complicações , Cefaleia/complicações , Cefaleia/terapia , Metanálise como Assunto , Revisões Sistemáticas como Assunto/métodos , Humanos , SARS-CoV-2
7.
Medicine (Baltimore) ; 100(50): e28298, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34918707

RESUMO

BACKGROUND: Melasma is a common acquired hyperpigmentation of the skin. The clinical manifestations are light brown or dark brown patches symmetrically distributed on the cheeks, forehead, and mandibular with different shades and unclear borders. The treatment of melasma is extremely challenging due to its easy relapse and hard to cure. As a classical method of traditional Chinese medicine, acupuncture has been used to treat melasma in clinical practice. However, there is no systematic review and meta-analysis of acupuncture on melasma. This study aims to assess the efficacy of acupuncture for melasma. METHODS: We will perform a comprehensive retrieval in the following electronic databases: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), Wan Fang Database, VIP database, Chinese Biomedical Literature Service System (SinoMed), Chinese Biomedicine (CBM) database, and TCM Literature Analysis from inception to July 1, 2021, to identify any eligible study. We include all randomized controlled trials (RCTs) without any limitation of blinding or publication language, and exclude cohort studies and case reports. The meta-analyses will be conducted by using the Stata16. We will use the Cochrane risk of bias tool for randomized trials to assess the risk of bias of included studies. The X2 and I2 tests will be utilized to assess the statistical heterogeneity of evidence. We will conduct a meta-analysis if the studies can be combined. Otherwise, a narrative synthesis will be performed. Article screening and data extraction will be independently evaluated by 2 reviewers trained in methodology according to the established selection criteria. Any disagreements between the 2 reviewers will be resolved by reaching a consensus with the other authors (the third reviewer). RESULTS: This study will systematically evaluate the clinical efficacy of acupuncture for melasma. CONCLUSION: The conclusion of this study will provide evidence to ensure the efficacy of acupuncture for melasma, so as to provide an objective and scientific basis for clinical practice. ETHICS AND DISSEMINATION: No ethical approval will be required because the data used are not linked to individual patient. The results of this review will be published in a peer-reviewed journal. REGISTRATION NUMBER: INPLASY2021110097.


Assuntos
Terapia por Acupuntura , Medicina Tradicional Chinesa , Melanose/terapia , Humanos , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
8.
Zhongguo Zhen Jiu ; 41(12): 1360-4, 2021 Dec 12.
Artigo em Chinês | MEDLINE | ID: mdl-34936275

RESUMO

OBJECTIVE: To observe the effect of umbilical moxibustion on phlegm damp constitution and intestinal flora, and explore the mechanism of umbilical moxibustion in improving phlegm damp constitution. METHODS: A total of 60 subjects with phlegm damp constitution were randomly divided into an observation group and a control group, 30 cases in each group. The control group was given TCM health guidance, such as diet and exercise; on the basis of the control group, umbilical moxibustion was applied in the observation group, 7 moxa cones each time, 2 times a week for 8 weeks. Before and after intervention, the indexes (transformation score of phlegm damp constitution, body mass, body mass index [BMI], waist circumference, hip circumference, heart rate and blood pressure) related to phlegm damp constitution were recorded in the two groups. The intestinal flora was detected with 16S rDNA sequencing technology in the two groups. RESULTS: After intervention, the transformation score of phlegm damp constitution, body mass, BMI, waist circumference and hip circumference were decreased compared before intervention in the observation group (P<0.001, P<0.01, P<0.05), the transformation score of phlegm damp constitution and waist circumference were decreased compared before intervention in the control group (P<0.001, P<0.05); the transformation score of phlegm damp constitution and waist circumference in the observation group were lower than the control group (P<0.001, P<0.05). After intervention, the relative abundance of Eubacterium hallii in the observation group was increased (P<0.01), the relative abundance of Blautia in the control group was decreased (P<0.05). CONCLUSION: Umbilical moxibustion may reshape the intestinal flora by up-regulating the relative abundance of Eubacterium hallii, thus improving phlegm damp constitution.


Assuntos
Microbioma Gastrointestinal , Moxibustão , Pontos de Acupuntura , Humanos , Muco
9.
J Am Chem Soc ; 143(33): 13167-13174, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34374520

RESUMO

A combination of conductive atomic force microscopy (AFM) and confocal fluorescence microscopy was used to measure photocurrents passing through single trimeric photosytem I (PSI) complexes located in the vicinity of single gold nanorods (AuNRs). Simultaneous excitation of PSI and of the AuNR longitudinal plasmon mode and detection of photocurrents from individual PSI in relation to the position of single AuNRs enable insight into plasmon-induced phenomena that are otherwise inaccessible in ensemble experiments. We have observed photocurrent enhancement by the localized plasmons by a factor of 2.9 on average, with maximum enhancement values of up to 8. Selective excitation of the longitudinal plasmon modes by the polarization of the excitation laser enables controllable switch-on of the photocurrent enhancement. The dependence of the extent of enhancement on the distance between PSI and AuNRs indicates that, apart from the enhancement of absorption, there is an additional enhancement mechanism affecting directly the electron transport process. The present study provides deeper insight into the molecular mechanisms of plasmon-enhanced photocurrents, not only in PSI but also potentially in other systems as well.

10.
Front Psychiatry ; 12: 772360, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35153851

RESUMO

BACKGROUND: Subthreshold depression refers to a state of mental sub-health that has depressive symptoms but does not meet the diagnostic criteria for major depressive disorder. It is a strong risk factor for depression and is related to an increase in suicide and mortality. Studies suggest that acupuncture may be effective in the treatment of subthreshold depression, but no evidence has proven that the efficacy of acupuncture for subthreshold depression is a specific therapeutic effect or a placebo effect. METHODS: This will be a prospective, randomized, controlled, and double-blind study of 64 patients with subthreshold depression. They will be randomly assigned as verum or minimal acupuncture group members. Patients in the verum acupuncture group will receive acupuncture at the acupoints, and those in the minimal acupuncture group will receive minimal acupuncture at non-acupoints. The interventions will be delivered over an 8-week period. The primary outcome measure will be the Hamilton Depression Scale-17 (HAMD-17). The secondary outcome measures will be the 9-item Patient Health Questionnaire (PHQ-9), 7-item Generalized Anxiety Disorder (GAD-7), and SF-12v2 Health Survey. The assessments will occur at baseline, 4 weeks, 8 weeks, and during a follow-up period. DISCUSSION: The protocol uses a randomized controlled trial to examine the effectiveness of acupuncture for subthreshold depression and to further study the mechanisms of its effect.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33376501

RESUMO

BACKGROUND: Acupuncture preconditioning was able to reduce the extent of ischaemia reperfusion (I/R) injury. Previous studies have shown that electroacupuncture (EA) pretreatment at T4-T5 Jiaji (EX-B2) acupoints had cardioprotective effects against myocardial I/R injury. However, the molecular mechanism remains inconclusive. METHODS: Wistar rats were pretreated with electroacupuncture for 7 days at the Neiguan (PC6), T4-T5 Jiaji (EX-B2), Yanglingquan (GB34), and Quchi (LI11) acupoints, which belong to different meridians. Then, we investigated the genome-wide gene expression profiles of rats prestimulated at these acupoints after I/R injury. RESULTS: Our study revealed previously unknown cardioprotective roles of T4-T5 Jiaji (EX-B2) acupoints in the I/R progression. The extent of myocardial injury was significantly decreased in the Jiaji group compared with the I/R group. In addition, our data are among the first to link the EA preconditioning at Neiguan (PC6) acupoints and circadian rhythm in the I/R model. Also, for the first time, we explored the meridian and acupoint specificity involved in EA pretreatment at the heart meridian, in which Yanglingquan and Quchi acupoints were selected as the control group for heart-divergent-meridian and nonheart-meridian acupoints. CONCLUSIONS: The present study suggested that EA pretreatment at Jiaji alters genome-wide gene expression and protects the rat myocardium against I/R injury, which are most likely through neurohumoral regulation.

12.
Medicine (Baltimore) ; 99(47): e23219, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217835

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease, which may develop gradually into nonalcoholic steatohepatitis, liver fibrosis, and cirrhosis. As a classical method of traditional Chinese medicine, acupuncture has been used to treat NAFLD in clinical practice. However, there is no systematic review and meta-analysis of acupuncture on NAFLD. There is an urgent need to evaluate the clinical efficacy of acupuncture for NAFLD. METHODS: We will perform a comprehensive retrieval in the following electronic databases: MEDLINE, Embase, Cochrane Library Central Register of Controlled Trials, PubMed, Science Citation Index Expanded (Web of Science), Epistemonikos, China National Knowledge Infrastructure (CNKI) database, Wanfang Data Knowledge Service Platform, Chinese Scientific Journals Database (VIP), Chinese Biomedical Literature Service System (SinoMed), and other databases from their inception to October 2020. We will select the qualified studies for data extraction and assess the quality and risk of bias, independently. The meta-analyses will be conducted by using the RevMan 5.3. RESULTS: This study will provide a reliable basis for the treatment of NAFLD with acupuncture. CONCLUSION: The findings will be an available reference to evaluate whether acupuncture is an effective intervention for patient with NAFLD. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/VFYXH.


Assuntos
Terapia por Acupuntura , Hepatopatia Gordurosa não Alcoólica/terapia , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
13.
Front Psychiatry ; 11: 564843, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061920

RESUMO

Butyrylcholinesterase (BChE) efficiently hydrolyzes acetylcholine (ACh) at high concentrations when acetylcholinesterase (AChE) is substrate-inhibited. Recent studies have shown that BChE also has a function that is independent of ACh, but it has not been fully explored. Low BChE expression is accompanied with higher stress-induced aggression and ghrelin levels in stress models, and BChE knockout mice exhibit cognitive and memory impairments. However, the role of BChE in posttraumatic stress disorder (PTSD) remains unclear. In the present study, we investigated the role of BChE in contextual fear memory and its regulatory effect on the expression of factors related to the glutamate (Glu)-glutamine (Gln) cycle via knockdown studies. We used AAVs and lentiviruses to knockdown BChE expression in the mouse hippocampal CA1 region and C8D1A astrocytes. Our behavioral data from those mice injected with AAV-shBChE in the hippocampal CA1 region showed strengthened fear memory and increased dendritic spine density. Elevated Glu levels and glutamine synthetase (GS) enzyme activity were detected in contextual fear conditioned-BChE knockdown animals and astrocytes. We observed that an AAV-shBChE induced lowering of BChE expression in the hippocampus CA1 region enhanced contextual fear memory expression and promoted the astrocytic Glu-Gln cycle but did not elevate ACh-hydrolyzing activity. This study provides new insight into the regulatory role of BChE in cognition and suggests potential target for stress-related psychiatric disorder such as PTSD where patients experience fear after exposure to severe life-threatening traumatic events.

14.
Nanomaterials (Basel) ; 10(7)2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32660111

RESUMO

We report optical characterization and theoretical simulation of plasmon enhanced methylammonium lead iodide (MAPbI 3 ) thin-film perovskite solar cells. Specifically, various nanohole (NH) and nanodisk (ND) arrays are fabricated on gold/MAPbI 3 interfaces. Significant absorption enhancement is observed experimentally in 75 nm and 110 nm-thick perovskite films. As a result of increased light scattering by plasmonic concentrators, the original Fabry-Pérot thin-film cavity effects are suppressed in specific structures. However, thanks to field enhancement caused by plasmonic resonances and in-plane interference of propagating surface plasmon polaritons, the calculated overall power conversion efficiency (PCE) of the solar cell is expected to increase by up to 45.5%, compared to its flat counterpart. The role of different geometry parameters of the nanostructure arrays is further investigated using three dimensional (3D) finite-difference time-domain (FDTD) simulations, which makes it possible to identify the physical origin of the absorption enhancement as a function of wavelength and design parameters. These findings demonstrate the potential of plasmonic nanostructures in further enhancing the performance of photovoltaic devices based on thin-film perovskites.

15.
Medicine (Baltimore) ; 98(48): e18025, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770216

RESUMO

INTRODUCTION: Sepsis is a physiological, pathological, and biochemical syndrome caused by infection. Acupuncture may be useful for sepsis. This systematic review aims to assess the efficacy and safety of acupuncture as a complementary therapy for sepsis. METHODS AND ANALYSIS: We will search PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), Wan Fang Database, Chinese Biomedicine (CBM) database, VIP database, and TCM Literature Analysis and Retrieval Database from inception to October 31, 2019 to identify any eligible study. We include all randomized controlled trials (RCTs) without any limitation of blinding or publication language, exclude cohort studies and case reports. Two reviewers will independently select studies, extract and manage data. The primary outcomes include the mortality at 28 days, acute physiology, and chronic health evaluation II scores. The secondary outcomes include the tumor necrosis factor α (TNF-α) counts, interleukin 6 (IL-6) counts, interleukin 10 (IL-10) counts, procalcitonin (PCT), lactic acid, the level of T cell subsets (CD3+, CD4+, CD8+, CD4+/CD8+), monocytes of human leukocyte antigen DR (HLA-DR), C-reactive protein (CRP), the numeration of leukocyte, intra-abdominal pressure, and adverse events or reactions. Statistical analyses will be performed using the Review Manager V.5.3 and R packages Metafor. We will use the Cochrane risk of bias tool for randomized trials to assess the risk of bias of included studies. ETHICS AND DISSEMINATION: This study will not involve personal information. Ethical approval will not be required. We will publish the results in a peer-reviewed journal. PROSPERO TRIAL REGISTRATION NUMBER: CRD42019141491.


Assuntos
Terapia por Acupuntura/métodos , Sepse/terapia , APACHE , Proteína C-Reativa/análise , Antígenos HLA-DR/sangue , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Ácido Láctico/sangue , Contagem de Leucócitos , Metanálise como Assunto , Pró-Calcitonina/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Sepse/sangue , Sepse/mortalidade , Revisões Sistemáticas como Assunto , Subpopulações de Linfócitos T/metabolismo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue
16.
J Med Chem ; 62(21): 9983-9989, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31408335

RESUMO

We unveiled an underside binding site on smoothened receptor (SMO) by a colocalization strategy using two structurally complementary photoaffinity probes derived from a known ligand Allo-1. Docking study and structural dissection identified key interactions within the site, including hydrogen bonding, π-π interactions, and hydrophobic interactions between Allo-1 and its contacting residues. Taken together, our results reveal the molecular base of Allo-1 binding and provide a basis for the design of new-generation ligands to overcome drug resistance.


Assuntos
Membrana Celular/metabolismo , Receptor Smoothened/química , Receptor Smoothened/metabolismo , Sítios de Ligação , Desenho de Fármacos , Modelos Moleculares , Sondas Moleculares/química , Sondas Moleculares/metabolismo , Domínios Proteicos , Transporte Proteico , Relação Estrutura-Atividade
17.
Chemistry ; 25(50): 11635-11640, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31368214

RESUMO

Disulfide-containing detergents (DCDs) are introduced, which contain a disulfide bond in the hydrophobic tail. DCDs form smaller micelles than corresponding detergents with linear hydrocarbon chains, while providing good solubilization and reconstitution of membrane proteins. The use of this new class of detergents in structural biology is illustrated with solution NMR spectra of the human G protein-coupled receptor A2A AR, which is an α-helical protein, and the ß-barrel protein OmpX from E. coli.


Assuntos
Proteínas da Membrana Bacteriana Externa/química , Detergentes/química , Proteínas de Escherichia coli/química , Hidrolases/química , Receptor A2A de Adenosina/química , Proteínas da Membrana Bacteriana Externa/metabolismo , Dissulfetos/química , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Humanos , Hidrolases/metabolismo , Micelas , Ressonância Magnética Nuclear Biomolecular , Estabilidade Proteica , Receptor A2A de Adenosina/metabolismo
18.
Sci Rep ; 9(1): 12221, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434993

RESUMO

Recent studies have shown that transforming microglia phenotype from pro-inflammation of M1 phenotype to anti-inflammation and tissue-repairing M2 phenotype may be an effective therapeutic strategy for preventing ischemic stroke brain injury. Isosteviol Sodium (STV-Na) has shown promise as a neuroprotective agent in cerebral ischemia model, although its effect on microglial polarization and chronic recovery after stroke is not clear. Here, we demonstrated that STV-Na treatment significantly reduced cerebral ischemic damage at both acute and chronic time points. STV-Na has a profound regulatory effect on microglia response after stroke. It can promote M2 polarization and inhibit microglia-mediated inflammation (M1) response following stroke in vivo and in vitro. Furthermore, we also found that Growth Arrest-Specific 5 (GAS5) altered OGD/R-induced microglial activation by increasing Notch1 expression via miR-146a-5p, the mRNA level of GAS5 and the protein level of Notch1 in vivo and in vitro, were discovered that both downgraded with STV-Na. Taken together, the present study demonstrated that STV-Na exerted neuroprotective effects by modulating microglia/macrophage polarization in ischemic stroke via the GAS5/miR-146a-5p sponge. These findings provide new evidence that targeting STV-Na could be a treatment for the prevention of stroke-related brain damage.


Assuntos
Isquemia Encefálica , Diterpenos do Tipo Caurano/farmacologia , Macrófagos , MicroRNAs/metabolismo , Microglia , RNA Longo não Codificante/metabolismo , Acidente Vascular Cerebral , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Isquemia Encefálica/prevenção & controle , Regulação da Expressão Gênica , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Microglia/metabolismo , Microglia/patologia , Receptor Notch1/biossíntese , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/prevenção & controle
19.
Zhen Ci Yan Jiu ; 44(4): 248-52, 2019 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-31056876

RESUMO

OBJECTIVE: To investigate the effect of "Jiaji"(EX-B2)-electroacupuncture(EA) preconditioning on structural changes of myocardium and expression of cytochrome P450 (CYP450) enzymes in acute myocardial ischemia-reperfusion injury (MIRI) rats. METHODS: Sixty male Wistar rats were randomly divided into sham operation, model, EX-B2, Neiguan (PC6), Yanglingquan(GB34) and Quchi (LI11) groups (n=10 in each group). The MIRI model was established by occlusion of the descending anterior branch of the left coronary artery for 30 min, followed by reperfusion for 30 min. EA preconditioning (2 Hz/100 Hz, 1 mA) was respectively applied to EX-B2, PC6, GB34, and LI11 for 30 min, once daily for 7 days. Morphological changes of myocardium were observed by H.E. staining. The ultrastructure of myocardial cells was observed by transmission electron microscope (TEM). The protein expression levels of myocardial CYP450 (CYP1A1, CYP2B2, CYP2C11 and CYP4A2) were detected by Western blot. RESULTS: In MIRI rats, myocardial pathological changes as swollen, disorganized arrangement, and partially ruptured myocardial fibers with unclear limit and necrosis and infiltration of lots of inflammatory cells under microscope, and focal myofilament degeneration, dissolution and necrosis with interstitial edema, vague mitochondria with swelling and vacuolation, ruptured and disorganized arrangement of crests under TEM were found in the ischemic area, which was obviously milder in rats of both EX-B2 and PC6 groups. After modeling, the expression of myocardial CYP1A1 and CYP2B2 protein were significantly up-regulated in the model group relevant to the sham operation group (P<0.05). In EA preconditioning groups, the expression levels of CYP1A1 and CYP4A2 proteins in the EX-B2, PC6 and GB34 groups were obviously down-regulated (P<0.01), and those of CYP2B2 and CYP2C11 proteins in both EX-B2 and PC6 groups were markedly up-regulated relevant to the model group (P<0.01). Compared with the EX-B2 group, the expression levels of CYP1A1, CYP4A2 proteins in the LI11 group were significantly up-regulated (P<0.05), and CYP2B2, CYP2C11 proteins were significantly down-regulated (P<0.05). No significant differences were found between the model and sham operation groups in the expression levels of myocardial CYP2C11 and CYP4A2 proteins, between the LI11 and model groups in the expression of CYP1A1, CYP2B2, CYP2C11 and CYP4A2, between the GB34 and model groups in the expression of CYP2B2, CYP2C11 (all P>0.05).. CONCLUSION: EA preconditioning at EX-B2 and PC6 can suppress MIRI induced up-regulation of myocardial CYP450 ω-hydroxylase CYP1A1 and CYP4A2 expression and further up-regulate the expression of myocardial epoxygenase CYP2B2 and CYP2C11 proteins in acute MIRI rats, thus playing a role in myocardial protection.


Assuntos
Eletroacupuntura , Pontos de Acupuntura , Animais , Sistema Enzimático do Citocromo P-450 , Masculino , Miocárdio , Ratos , Ratos Wistar
20.
Biomed Pharmacother ; 101: 371-378, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29499412

RESUMO

Right heart failure and pulmonary artery remodeling resulting from increased left heart pressure are prevalent in a clinical setting, and the specific pathological feature exhibits cancer-like cell proliferation in lung. STVNa has been previously demonstrated its anti-proliferation property. In this study, we want to verify the therapeutic effect of STVNa against right ventricle hypertrophy and pulmonary artery remodeling in rats induced by transverse aortic constriction (TAC). The results show that TAC surgery increased mean right ventricle pressure (mRVP) less in the STVNa group than that in the vehicle group (11.81 vs 22.71 mmHg/ml, p < 0.01). STVNa treatment reduced the right ventricle cardiomyocyte area (p < 0.05) and the proliferation of pathological smooth muscle cells proving by PCNA immunohistochemical staining. Gene expression of brain natriuretic peptide (BNP), smooth muscle actin (SMA) and CD31 assessed by real-time polymerase chain reaction were confirmed the above results. Also, STVNa treatment decreased the lung fibrosis content and alleviated the inflammation infiltration. The expression of ET-1 and the phosphorylation of signal-regulated kinase (ERK) were lower in STVNa group compared to vehicle group (p < 0.05). In summary, STVNa could relieve right ventricle hypertrophy and pulmonary artery remodeling formation in rats after 9 weeks of TAC surgery by reducing ET-1 expression and suppressing ERK phosphorylation signal and subsequently inhibiting cell proliferation.


Assuntos
Diterpenos do Tipo Caurano/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Hipertrofia Ventricular Direita/tratamento farmacológico , Artéria Pulmonar/efeitos dos fármacos , Animais , Estenose da Valva Aórtica/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Constrição , Coração/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Hipertensão Pulmonar/tratamento farmacológico , Pulmão/efeitos dos fármacos , Masculino , Miócitos de Músculo Liso/efeitos dos fármacos , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
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