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1.
Cardiology ; 149(1): 78-92, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37708863

RESUMO

INTRODUCTION: The main aim of this study was to investigate the impact of isolated coronary microvascular disease (CMD) as diagnosed via various modalities on prognosis. METHODS: A systematic literature review of PubMed, Embase, and Cochrane Library databases was conducted to identify relevant studies published up to March 2023. Included studies were required to measure coronary microvascular function and report outcomes in patients without obstructive coronary artery disease (CAD) or any other cardiac pathological characteristics. The primary endpoint was all-cause mortality, and the secondary endpoint was a major adverse cardiac event (MACE). Pooled effects were calculated using random effects models. RESULTS: A total of 27 studies comprising 18,204 subjects were included in the meta-analysis. Indices of coronary microvascular function measurement included coronary angiography-derived index of microcirculatory resistance (caIMR), hyperemic microcirculatory resistance (HMR), coronary flow reserve (CFR), and so on. Patients with isolated CMD exhibited a significantly higher risk of mortality (OR: 2.97, 95% CI, 1.91-4.60, p < 0.0001; HR: 3.38, 95% CI, 1.77-6.47, p = 0.0002) and MACE (OR: 5.82, 95% CI, 3.65-9.29, p < 0.00001; HR: 4.01, 95% CI, 2.59-6.20, p < 0.00001) compared to those without CMD. Subgroup analysis by measurement modality demonstrated consistent and robust pooled effect estimates in various subgroups. CONCLUSION: CMD is significantly associated with an elevated risk of mortality and MACE in patients without obstructive CAD or any other identifiable cardiac pathologies. The utilization of various measurement techniques may have potential advantages in the management of isolated CMD.


Assuntos
Doença da Artéria Coronariana , Humanos , Angiografia Coronária/métodos , Microcirculação , Doença da Artéria Coronariana/complicações , Prognóstico
2.
Insect Biochem Mol Biol ; 157: 103964, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37230333

RESUMO

Metamorphosis is one of the most important physiological processes in insects, which is coordinated by juvenile hormone (JH) and 20-hydroxyecdysone (20E). Ecdysone receptor (EcR) is a steroid receptor (SR), which usually presents in cytoplasm and transfers into nucleus after binding to 20E. Heat shock proteins (Hsps) are suggested to be important members of the SR complex. However, their role in nucleocytoplasmic shuttle of the EcR remains unclear. In the present study, we found that apoptozole (Hsp70 inhibitor) suppressed the larval molting by decreasing the expression of ecdysone signaling genes. Two cytoplasmic (Cy) Hsp70s (Hsp72 and Hsp73) interacted with both EcR and ultraspiracle (USP, the heterodimer partner of EcR). By immunohistochemistry experiments, we revealed that CyHsp70 co-localized with EcR in the cytoplasm, and that both apoptozole and interfering of CyHsp70 significantly inhibited the process of EcR entering the nucleus under 20E induction, while reducing the expression of ecdysone signaling genes. Interestingly, the nuclear localization of EcR was also promoted by two other stimuli, including JH and heat stress, and this promotion was inhibited by apoptozole. This implies that various stimuli can induce EcR entry into the nucleus, and that this process is mediated by CyHsp70. Curiously, neither JH nor heat stress activated the ecdysone signaling genes; instead, they have a significant inhibitory effect on them. Taken together, it seems that Cytoplasmic Hsp70s promote EcR transport into the nucleus by responding to various stimuli, and that the biological effects of various stimuli passing through the EcR are different. Thus, our data provide a new viewpoint to understand the mechanism of nucleocytoplasmic shuttle of EcR.


Assuntos
Proteínas de Drosophila , Receptores de Esteroides , Animais , Ecdisona , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Ecdisterona/metabolismo , Metamorfose Biológica/genética , Hormônios Juvenis/metabolismo , Citoplasma/metabolismo , Proteínas de Drosophila/genética
3.
Curr Pharm Des ; 28(23): 1902-1910, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35400334

RESUMO

BACKGROUND: Direct oral anticoagulants (DOACs) are the guideline-recommended therapy for some hypercoagulable diseases but are used off-label for left ventricular thrombus (LVT) owing to a paucity of evidence. We performed a meta-analysis to assess the safety and efficacy of DOACs compared with vitamin K antagonists (VKAs) for LVT treatment. METHODS: We comprehensively searched PubMed, EMBASE, Cochrane Library, and Web of Science databases for studies that compared DOACs with VKAs for LVT treatment. Outcome indicators included stroke or systemic embolism (SSE), thrombus resolution, bleeding, and death. The Newcastle-Ottawa scale was used to evaluate the quality of included studies. Data were analyzed using Review Manager 5.3, and the meta-analysis is registered at PROSPERO (CRD 42020211376). RESULTS: We included 12 observational studies (n = 2262 patients). SSE was similar for DOACs and VKAs groups (odds ratio (OR) = 1.01, 95% confidence interval (CI) 0.66-1.54, P = 0.95). For thrombus resolution, DOACs were not significantly different to VKAs (OR = 1.15, 95% CI 0.54-2.45, P = 0.71). DOACs and VKAs had a similar bleeding risk (OR = 0.78, 95% CI 0.45-1.35, P = 0.37). DOACs and VKAs groups had a comparable mortality (OR = 0.91, 95% CI 0.50-1.65, P = 0.76). Subgroup analysis showed that post-acute myocardial infarction (AMI) patients using DOACs had a lower risk of SSE (OR = 0.24, 95% CI 0.07-0.87, P = 0.03) and bleeding (OR = 0.38, 95% CI 0.18-0.81, P = 0.01). CONCLUSION: DOACs and VKAs showed no difference in the safety and efficacy of patients with LVT. DOACs might be superior to VKAs for LVT treatment in post-AMI patients.


Assuntos
Acidente Vascular Cerebral , Trombose , Administração Oral , Anticoagulantes/uso terapêutico , Fibrinolíticos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Trombose/tratamento farmacológico , Vitamina K
4.
Medicine (Baltimore) ; 100(45): e27812, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34766592

RESUMO

RATIONALE: Takotsubo syndrome (TTS) is characterized by transient and reversible left ventricular systolic dysfunction, which are often associated with acute physical or emotional stressors. Cancer is one of the comorbidities in TTS, and TTS is even considered as a paraneoplastic syndrome, but its mechanism remains unclear. We report a patient in whom cancer and untreated mental disorders triggered TTS. PATIENT CONCERNS: A 59-year-old man was transferred to the Department of Cardiology because of acute onset of severe chest pain and dyspnea before cystoscopy. He presented with hematuria, had been diagnosed with a high-grade urothelial bladder cancer, and underwent transurethral resection of bladder tumors 4 months previously. He had severe anxiety regarding recurrence and death from cancer, especially after the hematuria recurred. DIAGNOSIS: TTS and severe anxiety. INTERVENTIONS: The results of coronary angiography, a left ventriculogram, echocardiography, and the clinical outcome led to the diagnosis of TTS. The patient was treated with extracorporeal membrane oxygenation support, mechanical ventilation, and drugs for heart failure and anxiety. OUTCOMES: Echocardiography showed normal wall motion on day 6 of symptom onset. Six months after symptom onset, the anxiety score was reduced from 12 to 11, and the patient had no episodes of any discomfort, and no evidence of cancer recurrence was observed. LESSONS: Patients with cancer and TTS have a higher level of stress, and physicians need to pay more attention to early screening and early treatment of mental disorders in these patients. Prompt and effective multidisciplinary treatment, including psychological counseling and antianxiety drugs, can improve the prognosis in such cases.


Assuntos
Preparações Farmacêuticas , Cardiomiopatia de Takotsubo , Ansiedade/complicações , Hematúria , Humanos , Masculino , Pessoa de Meia-Idade , Choque Cardiogênico , Cardiomiopatia de Takotsubo/complicações , Cardiomiopatia de Takotsubo/diagnóstico
5.
Chemistry ; 27(65): 16145-16152, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34595784

RESUMO

Site specific installation of a paramagnetic ion with magnetic anisotropy in a biomolecule generates valuable structural restraints, such as pseudocontact shifts (PCSs) and residual dipolar couplings (RDCs). These paramagnetic effects can be used to characterize the structures, interactions and dynamics of biological macromolecules and their complexes. Two single-armed DOTA-like tags, BrPSPy-DO3M(S)A-Ln and BrPSPy-6M-DO3M(S)A-Ln, each containing a thiol-specific reacting group, that is, a phenylsulfonyl pyridine moiety, are demonstrated as rigid, reactive and stable paramagnetic tags for protein modification by formation of a reducing resistant thioether bond between the protein and the tag. The two tags present high reactivity with the solvent exposed thiol group in aqueous solution at room temperature. The introduction of Br at the meta-position in pyridine enhances the reactivity of 4-phenylsulfonyl pyridine towards the solvent exposed thiol group in a protein, whereas the ortho-methyl group in pyridine increases the rigidity of the tag in the protein conjugates. The high performance of these two tags has been demonstrated in different cysteine mutants of ubiquitin and GB1. The high reactivity and rigidity of these two tags can be added in the toolbox of paramagnetic tags suitable for the high-resolution NMR measurements of biological macromolecules and their complexes.


Assuntos
Elementos da Série dos Lantanídeos , Ressonância Magnética Nuclear Biomolecular , Proteínas , Piridinas , Compostos de Sulfidrila
6.
BMC Cardiovasc Disord ; 21(1): 372, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344308

RESUMO

BACKGROUND: Complete atrioventricular block (AVB) is a life-threatening condition that usually occurs in elderly people with organic heart disease. We herein describe a rare case of complete AVB in a young man with hypertrophic obstructive cardiomyopathy (HOCM) complicated by cholecystitis and cholangitis. Both cardio-biliary reflex and alcohol septal ablation (ASA) can cause conduction block, but the latter is often irreversible. However, their simultaneous occurrence in a patient has not been reported. CASE PRESENTATION: A 31-year-old man presented with acute cholecystitis and cholangitis and complete AVB, which had been diagnosed at a local hospital on the third day after onset. On the fourth day, he was transferred to the emergency department of our hospital because of persistent complete AVB, although his abdominal pain had been partially relieved. An echocardiogram showed a remarkably elevated left ventricular outflow tract (LVOT) gradient (105.2 mmHg) despite the performance of ASA 9 years previously. The abdominal pain gradually disappeared, and normal sinus rhythm was completely recovered 11 days after onset. We determined that cardio-biliary reflex was the cause of the AVB because of the absence of other common causes. Finally, the patient underwent implantation of a permanent pacemaker to reduce the LVOT obstruction and avoid the risk of AVB recurrence. CONCLUSIONS: Cholecystitis is a rare cause of complete AVB, which is a difficult differential diagnosis when complicated by HOCM after ASA. Clinicians should be alert to the possibility of cholecystitis in patients with abdominal pain and an unknown cause of bradycardia, complete AVB, or even sinus arrest.


Assuntos
Técnicas de Ablação/métodos , Bloqueio Atrioventricular/etiologia , Cardiomiopatia Hipertrófica/complicações , Colecistite/complicações , Reflexo , Doença Aguda , Adulto , Bloqueio Atrioventricular/diagnóstico , Bloqueio Atrioventricular/terapia , Bloqueio de Ramo/diagnóstico , Colangite/complicações , Colecistite/diagnóstico por imagem , Ecocardiografia , Eletrocardiografia , Etanol/uso terapêutico , Humanos , Masculino , Obstrução do Fluxo Ventricular Externo/diagnóstico por imagem , Obstrução do Fluxo Ventricular Externo/terapia
7.
Phys Chem Chem Phys ; 21(20): 10217-10227, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-30860214

RESUMO

Triarylmethyl (TAM or trityl) radicals are becoming important for measuring distances in proteins and nucleic acids. Here, we report on a new trityl spin label CT02MA, which conjugates to a protein via a redox stable thioether bond. The performance of the new spin label was demonstrated in W-band double electron-electron resonance (DEER) distance measurements on doubly trityl-labelled mutants of immunoglobulin G-binding protein 1 (GB1) and ubiquitin. For both doubly CT02MA-labelled proteins we measured, by applying chirped pump pulse(s), relatively narrow distance distributions, comparable to those obtained with the same protein mutants doubly labelled with BrPy-DO3MA-Gd(iii). We noticed, however, that the sample contained some free CT02MA that was difficult to remove at the purification step. Dual labelling of ubiquitin with one CT02MA tag and one BrPy-DO3MA-Gd(iii) tag was achieved as well and the trityl-Gd(iii) distance distribution was measured, facilitated by the use of a dual mode cavity in combination with a chirped pump pulse. We also measured the Gd(iii)-Gd(iii) distance distribution in this sample, showing that the labelling procedure was not fully selective. Nevertheless, these measurements demonstrate the potential of the high sensitivity Gd(iii)-trityl W-band DEER distance measurements in proteins, which can be further exploited by designing orthogonal Gd(iii)/trityl labelling schemes.


Assuntos
Técnicas de Química Analítica/métodos , Espectroscopia de Ressonância de Spin Eletrônica , Gadolínio/química , Proteínas/análise , Marcadores de Spin , Proteínas de Transporte/análise , Proteínas de Transporte/genética , Mutação , Proteínas/química , Proteínas/genética , Ubiquitina/análise , Ubiquitina/genética
8.
J Phys Chem Lett ; 9(20): 6119-6123, 2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30277780

RESUMO

Distance measurements by electron-electron double resonance (DEER) carried out on spin-labeled proteins delivered into cells provide new insights into the conformational states of proteins in their native environment. Such measurements depend on spin labels that exhibit high redox stability and high DEER sensitivity. Here we present a new Gd(III)-based spin label, BrPSPy-DO3A-Gd(III), which was derived from an earlier label, BrPSPy-DO3MA-Gd(III), by removing the methyl group from the methyl acetate pending arms. The small chemical modification led to a reduction in the zero-field splitting and to a significant increase in the phase memory time, which together culminated in a remarkable improvement of in-cell DEER sensitivity, while maintaining the high distance resolution. The excellent performance of BrPSPy-DO3A-Gd(III) in in-cell DEER measurements was demonstrated on doubly labeled ubiquitin and GB1 delivered into HeLa cells by electroporation.

9.
J Biomol NMR ; 70(2): 77-92, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29224182

RESUMO

Organic synthesis of a ligand with high binding affinities for paramagnetic lanthanide ions is an effective way of generating paramagnetic effects on proteins. These paramagnetic effects manifested in high-resolution NMR spectroscopy are valuable dynamic and structural restraints of proteins and protein-ligand complexes. A paramagnetic tag generally contains a metal chelating moiety and a reactive group for protein modification. Herein we report two new DTPA-like tags, 4PS-PyDTTA and 4PS-6M-PyDTTA that can be site-specifically attached to a protein with a stable thioether bond. Both protein-tag adducts form stable lanthanide complexes, of which the binding affinities and paramagnetic tensors are tunable with respect to the 6-methyl group in pyridine. Paramagnetic relaxation enhancement (PRE) effects of Gd(III) complex on protein-tag adducts were evaluated in comparison with pseudocontact shift (PCS), and the results indicated that both 4PS-PyDTTA and 4PS-6M-PyDTTA tags are rigid and present high-quality PREs that are crucially important in elucidation of the dynamics and interactions of proteins and protein-ligand complexes. We also show that these two tags are suitable for in-situ protein NMR analysis.


Assuntos
Espectroscopia de Ressonância de Spin Eletrônica/métodos , Ácido Pentético/química , Proteínas/química , Quelantes/química , Elementos da Série dos Lantanídeos/química , Ressonância Magnética Nuclear Biomolecular/métodos , Ligação Proteica , Sulfetos/química
10.
Phys Chem Chem Phys ; 19(39): 26944-26956, 2017 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-28956044

RESUMO

High-affinity chelating tags for Gd(iii) and Mn(ii) ions that provide valuable high-resolution distance restraints for biomolecules were used as spin labels for double electron-electron resonance (DEER) measurements. The availability of a generic tag that can bind both metal ions and provide a narrow and predictable distance distribution for both ions is attractive owing to their different EPR-related characteristics. Herein we introduced two paramagnetic tags, 4PSPyMTA and 4PSPyNPDA, which are conjugated to cysteine residues through a stable thioether bond, forming a short and, depending on the metal ion coordination mode, a rigid tether with the protein. These tags exhibit high affinity for both Mn(ii) and Gd(iii) ions. The DEER performance of the 4PSPyMTA and 4PSPyNPDA tags, in complex with Gd(iii) or Mn(ii), was evaluated for three double cysteine mutants of ubiquitin, and the Gd(iii)-Gd(iii) and Mn(ii)-Mn(ii) distance distributions they generated were compared. All three Gd(iii) complexes of the ubiquitin-PyMTA and ubiquitin-PyNPDA conjugates produced similar and expected distance distributions. In contrast, significant variations in the maxima and widths of the distance distributions were observed for the Mn(ii) analogs. Furthermore, whereas PyNPDA-Gd(iii) and PyNPDA-Mn(ii) delivered similar distance distributions, appreciable differences were observed for two mutants with PyMTA, with the Mn(ii) analog exhibiting a broader distance distribution and shorter distances. ELDOR (electron-electron double resonance)-detected NMR measurements revealed some distribution in the Mn(ii) coordination environment for the protein conjugates of both tags but not for the free tags. The broader distance distributions generated by 4PSPyMTA-Mn(ii), as compared with Gd(iii), were attributed to the distributed location of the Mn(ii) ion within the PyMTA chelate owing to its smaller size and lower coordination number that leave the pyridine nitrogen uncoordinated. Accordingly, in terms of distance resolution, 4PSPyNPDA can serve as an effective generic tag for Gd(iii) and Mn(ii), whereas 4PSPyMTA is efficient for Gd(iii) only. This comparison between Gd(iii) and Mn(ii) suggests that PyMTA model compounds may not predict sufficiently well the performance of PyMTA-Mn(ii) as a tag for high-resolution distance measurements in proteins because the protein environment can influence its coordination mode.


Assuntos
Espectroscopia de Ressonância de Spin Eletrônica , Proteínas/química , Quelantes , Cisteína , Elétrons , Gadolínio , Íons , Espectroscopia de Ressonância Magnética , Manganês , Marcadores de Spin , Ubiquitina
11.
Angew Chem Int Ed Engl ; 56(11): 2914-2918, 2017 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-28145030

RESUMO

The cellular environment of proteins differs considerably from in vitro conditions under which most studies of protein structures are carried out. Therefore, there is a growing interest in determining dynamics and structures of proteins in the cell. A key factor for in-cell distance measurements by the double electron-electron resonance (DEER) method in proteins is the nature of the used spin label. Here we present a newly designed GdIII spin label, a thiol-specific DOTA-derivative (DO3MA-3BrPy), which features chemical stability and kinetic inertness, high efficiency in protein labelling, a short rigid tether, as well as favorable spectroscopic properties, all are particularly suitable for in-cell distance measurements by the DEER method carried out at W-band frequencies. The high performance of DO3MA-3BrPy-GdIII is demonstrated on doubly labelled ubiquitin D39C/E64C, both in vitro and in HeLa cells. High-quality DEER data could be obtained in HeLa cells up to 12 h after protein delivery at in-cell protein concentrations as low as 5-10 µm.


Assuntos
Complexos de Coordenação/química , Gadolínio/química , Ubiquitina/análise , Espectroscopia de Ressonância de Spin Eletrônica , Células HeLa , Humanos , Estrutura Molecular
12.
Insect Sci ; 22(1): 95-105, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24395766

RESUMO

Ecdysone receptor (EcR) and ultraspiracle (USP) form heterodimers to mediate ecdysteroid signaling during molting and metamorphosis. Various EcR/USP heterodimers have been reported. However, it is unclear what kind of EcR/USP combination is adopted by lepidopteran insects during the larval-pupal metamorphosis and whether the EcR/USP heterodimer varies among different tissues. To address these questions, two isoforms of each EcR and USP were cloned from the common cutworm, their messenger RNA expression patterns were examined by real-time quantitative polymerase chain reaction in different tissues during the larval-pupal metamorphosis and in the midgut in response to hormonal induction. Furthermore, their subcellular localization and protein-protein interaction were explored by transient expression and far-western blotting, respectively. All the four genes were significantly up-regulated in prepuae and/or pupae. The expression profiles of EcRB1 and USP1 were nearly identical to each other in the epidermis, fat body and midgut, and a similar situation also applied to EcRA and USP2. The three genes responded to 20-hydroxyecdysone (20E) induction except for USP2, and USP1 could be up-regulated by both 20E and juvenile hormone. The four proteins mainly localized in the nucleus and the nuclear localization was promoted by 20E. The protein-protein interaction between each EcR and USP was found in vitro. These results suggest that two types of EcR/USP heterodimer (EcRA/USP2 and EcRB1/USP1) may exist simultaneously in the common cutworm, and the latter should play more important roles during the larval-pupal metamorphosis. In addition, the types of EcR/USP heterodimer do not vary in the tissues which undergo histolysis and regeneration during metamorphosis.


Assuntos
Mariposas/fisiologia , Isoformas de Proteínas/metabolismo , Receptores de Esteroides/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Ecdisterona/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Insetos , Hormônios Juvenis/metabolismo , Larva/crescimento & desenvolvimento , Larva/metabolismo , Metamorfose Biológica/fisiologia , Dados de Sequência Molecular , Muda/fisiologia , Mariposas/genética , Isoformas de Proteínas/genética , Pupa/crescimento & desenvolvimento , Pupa/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Esteroides/genética , Fatores de Transcrição/genética
13.
J Insect Physiol ; 61: 34-41, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24406661

RESUMO

Heat shock protein (Hsp) and its cognate protein (Hsc) play important roles in helping insects survive extreme temperatures. However, high level of Hsp expression usually brings negative physiological effects on organisms. The mechanism of this trade-off is unclear. In this study, a lepidopteran insect, the common cutworm Spodoptera litura, was stressed at different temperatures, and the impact on both thermotolerance and fecundity was examined. The mRNA levels of four Hsp/Hscs (Hsp90, Hsc90, Hsp70 and Hsc70) and two ecdysone receptors (EcRs, EcRA and EcRB1) in different stresses and during the larval-pupal metamorphosis were determined. The results revealed that the pre-acclamation at mild stress increased the thermotolerance but decreased the egg production in adults. During the stress process, the mRNA levels of all the Hsp/Hsc and ecdysone receptor genes were significantly up-regulated. The two Hsp/Hsc70s and EcRs revealed consistent expression profiles with each other during the larval-pupal metamorphosis. Co-immunoprecipitation and Western blotting analysis indicated that Hsp/Hsc70 interacted with EcRs. RNAi of Hsc70 decreased the mRNA levels of two 20E-induced genes such as E74B and E75. Hsp70 transferred from the cytoplasm to nucleus in response to cold stress. These data together suggest that Hsp/Hsc70 might be involved in the regulation of 20E signaling, and the protein-protein interaction between Hsp/Hsc70 and EcRs probably act as a bridge mediating the trade-off between high thermotolerance and physiological defects.


Assuntos
Regulação da Expressão Gênica , Proteínas de Choque Térmico/genética , Resposta ao Choque Térmico , Proteínas de Insetos/genética , Receptores de Esteroides/genética , Spodoptera/fisiologia , Animais , Western Blotting , Proteínas de Choque Térmico/metabolismo , Imunoprecipitação , Proteínas de Insetos/metabolismo , Larva/genética , Larva/fisiologia , Metamorfose Biológica , Pupa/genética , Pupa/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Esteroides/metabolismo , Reprodução , Spodoptera/genética , Spodoptera/crescimento & desenvolvimento
14.
Insect Biochem Mol Biol ; 43(9): 794-808, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23796435

RESUMO

Larval cuticle is degraded and replaced by the pupal counterpart during larval-pupal metamorphosis in the holometabolous insects. In addition to the extrinsic transformation, the epidermis goes through significant changes at molecular levels. To elucidate the intrinsic mechanism of epidermal metamorphosis, the dynamics of chitin content in the cuticle was examined in an important agricultural lepidopteran, the common cutworm, and the transcriptome was analyzed using Illumina sequencing technology. Gene expression profiles during the metamorphosis were further studied by both the digital gene expression (DGE) system and real-time quantitative PCR. The results showed that the chitin content decreased in prepupae and then increased in pupae. A total of 58 million sequencing reads were obtained and assembled into 70,346 unigenes. Over 9000 unigenes were identified to express differentially during the transformation process. As compared with the 6th instar feeding larvae, the most significant changes took place in the proteasome and metabolic pathways in prepupae and pupae, respectively. The cytochrome P450s, VHDLs, chitinase, serine protease and genes involved in sex pheromone biosynthesis changed their mRNA levels remarkably. Three chitinolytic enzymes (chitinase, ß-N-acetylglucosaminidase and chitin deacetylase) showed distinct mRNA expression patterns, the former two enzymes revealed the highest expression in prepupae, however the latter one showed its climax mRNA level in pupae. The gene expression patterns suggest that chitinase and ß-N-acetylglucosaminidase may be responsible for the degradation of larval cuticles, whereas chitin deacetylase may help to degrade the pupal counterparts. Gene expression dynamics also implied that the chitin of pupal cuticle might be formed by recycling of the degraded chitin of larval cuticle rather than through de novo synthesis. The 20E-induced nuclear receptors seem to be important factors regulating chitin metabolic enzymes during the cuticle remodeling. Our data provide a comprehensive resource for exploring the molecular mechanism of epidermal metamorphosis in insects.


Assuntos
Epiderme/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Insetos/genética , Larva/metabolismo , Pupa/metabolismo , Spodoptera/crescimento & desenvolvimento , Spodoptera/genética , Transcriptoma , Animais , Quitina/genética , Quitina/metabolismo , Epiderme/crescimento & desenvolvimento , Proteínas de Insetos/metabolismo , Larva/genética , Larva/crescimento & desenvolvimento , Dados de Sequência Molecular , Pupa/genética , Pupa/crescimento & desenvolvimento , Spodoptera/metabolismo
15.
J Zhejiang Univ Sci B ; 13(8): 638-44, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22843184

RESUMO

OBJECTIVE: To investigate the relationship between renal function and clinical outcomes among patients with acute ST-segment elevation myocardial infarction (ASTEMI), who were treated with emergency percutaneous coronary intervention (PCI). METHODS: 420 patients hospitalized in Peking University First Hospital, diagnosed with ASTEMI treated with emergency (PCI) from January 2001 to June 2011 were enrolled in this study. Estimated glomerular filtration rate (eGFR) was used as a measure of renal function. We compared the clinical parameters and outcomes between ASTEMI patients combined renal insufficiency and the patients with normal renal function. RESULTS: There was a significant increase in the concentrations of fibrinogen and D-Dimer (P<0.05) and a much higher morbidity of diabetes mellitus in the group of patients with chronic kidney disease (CKD; eGFR<60 ml/(min·1.73 m(2))) (P<0.01). CKD (eGFR<60 ml/(min·1.73 m(2))) was an independent predictor of in-hospital mortality for patients hospitalized with ASTEMI receiving PCI therapy rapidly (P=0.032, odds ratio (OR) 4.159, 95% confidence interval (CI) 1.127-15.346). CONCLUSIONS: Renal insufficiency is an independent predictor of in-hospital mortality for patients hospitalized with ASTEMI treated with primary PCI.


Assuntos
Infarto do Miocárdio/diagnóstico , Insuficiência Renal/diagnóstico , Idoso , Dimerização , Eletrocardiografia/métodos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/química , Fibrinogênio/química , Taxa de Filtração Glomerular , Hospitalização , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Intervenção Coronária Percutânea/métodos , Insuficiência Renal/complicações , Insuficiência Renal/mortalidade , Estudos Retrospectivos , Resultado do Tratamento
16.
J Zhejiang Univ Sci B ; 13(3): 231-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22374616

RESUMO

BACKGROUND AND OBJECTIVE: In clinical practice, the standard of secondary prevention for coronary heart disease (CHD) is quite disappointing in China. The physicians' shortage of knowledge of secondary prevention guidelines is thought to be a key factor contributing to the inadequate and delayed translation of guidelines into clinical practice. The purpose of this study is to investigate the influence of physicians' characteristics, including their education and work experience, on their knowledge of secondary prevention in China. METHODS: A representative questionnaire survey was made of physicians from cardiology departments in 35 tertiary hospitals in China. The survey contained 19 questions on knowledge of guideline recommendations for the secondary prevention of CHD. We collected basic information about the physicians, including their educational degree, clinical practice duration/work experience and geographic region. RESULTS: In total, 864 physicians participated in the survey. Eight hundred and thirty-seven completed questionnaires were analyzed. For 6 of the 19 questions, physicians with a postgraduate degree were more likely to answer correctly than those without such a degree. For 11 of the 19 questions, physicians with more than three years' clinical experience were more likely to answer correctly than those who had less than three years' experience. For 5 of the 19 questions, physicians from eastern areas were more likely to answer correctly than those from mid/western areas. The mean total score of correct answers to the questionnaire was 11.69 points. Educational degree and clinical practice duration affected total scores significantly while practice location did not (ß=0.500, P=0.004; ß=0.979, P=0.000; and ß=0.228, P=0.162, respectively). Even if a relatively low score of 12 is taken as a threshold level of acceptable knowledge (defined as a pass), the pass rate of all physicians was only 53.9%. Educational degree and clinical practice duration affected pass rate significantly while practice location did not (95% CI: 1.222-2.248, P=0.001; 95% CI: 1.773-3.140, P=0.000; and 95% CI: 0.993-1.758, P=0.056, respectively). CONCLUSIONS: Physicians with a clinical practice duration of more than three years knew more about secondary prevention guidelines than those with less experience. Physicians with a postgraduate degree knew more about secondary prevention guidelines than those without a postgraduate degree. However, overall knowledge of secondary prevention guidelines for CHD was poor among this group of physicians from tertiary hospitals.


Assuntos
Doença das Coronárias/prevenção & controle , Prevenção Secundária/métodos , China , Competência Clínica , Estudos Transversais , Educação Médica , Humanos , Médicos , Guias de Prática Clínica como Assunto , Prevenção Secundária/normas , Inquéritos e Questionários
17.
Zhonghua Xin Xue Guan Bing Za Zhi ; 37(1): 53-5, 2009 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-19671354

RESUMO

OBJECTIVE: Cardiovascular event is common and is an important cause of death for patients with chronic kidney disease (CKD). The purpose of current study is to analyze the related risk factors of cardiovascular event in patients with CKD. METHODS: Clinical data from 557 patients with CKD (stage III-V) who hospitalized in our hospital from Jan 2006 to Dec 2006 were retrospectively analyzed focusing on the risk factors of cardiovascular event and their impacts on death. RESULTS: Among the 557 patients with CKD, 332 were male and 225 were female. There were totally 163 patients (163/557, 29.3%) suffered from cardiovascular events during hospitalization. The independent risk factors for cardiovascular event were age, history of coronary heart disease, anemia and fasting blood glucose level. The mortality was significantly higher in patients suffered from cardiovascular events than that in patients without cardiovascular events (9.82% vs. 2.28%, P<0.001). CONCLUSIONS: For patients with CKD, anemia is another independent risk factor for cardiovascular events besides traditional risk factors and the mortality was significantly higher in CKD patients with cardiovascular events compared to CKD patients without cardiovascular events.


Assuntos
Doenças Cardiovasculares/etiologia , Falência Renal Crônica/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/complicações , Anemia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
18.
Beijing Da Xue Xue Bao Yi Xue Ban ; 41(2): 144-7, 2009 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-19377619

RESUMO

OBJECTIVE: To study the effects of chemokine-like factor 1(CKLF1)-plasmid transfer on cardiac function in a rat acute myocardial infarction (AMI) model. METHODS: Thirty male SD rats were randomly devided into 3 groups. One hundred micrograms of CKLF1-plasmid, empty plasmid or saline were injected intramuscularly with in vivo electroporation, respectively. Rats were subjected to left coronary artery ligation on the 6th day after gene transfer. Ultrasonic cardiography and hemodynamics were conducted and evaluated on the 22nd day after gene transfer. Then, the animals were sacrificed for determination of percentage of myocardial infarcion. RESULTS: The left ventricular ejection fraction in CKLF1 group (67.02% +/- 12.24%) was significantly higher than that in the saline group (43.64% +/- 7.82%) and empty plasmid group (47.56% +/- 4.10%), P<0.05. Fractional shortening of left ventricle in CKLF1 group (33.83% +/- 10.15%) was higher than that in saline group (18.49% +/- 3.96%) and empty plasmid group (20.85% +/- 2.24%), P<0.05. The maximal velocity of left ventricular pressure ascensus was higher in CKLF1 group [(5 720.01 +/- 826.32) mmHg/s, 1 mmHg=0.133 kPa] than in saline group [(3 955.69 +/- 685.91) mmHg/s] and in empty plasmid group [(4 412.03 +/- 500.74) mmHg/s)], P<0.05. And the maximal velosity of left ventricular pressure descensus was higher in CKLF1 group [(4 636.23 +/- 407.17) mmHg/s] than in saline group [(2 984.82 +/- 615.24) mmHg/s] and in empty plasmid group [(2 963.87 +/- 419.36) mmHg/s], P<0.05. While the percentage of myocardial infarction in CKLF1 group (29.63% +/- 3.93%) was smaller than that in saline group (38.01% +/- 5.48%) and in empty plasmid group (37.50% +/- 6.33%), P<0.05. CONCLUSION: CKLF1 gene transfer can limit the mass of myocardial infarction and improve post-infarction cardiac function.


Assuntos
Quimiocinas/genética , Técnicas de Transferência de Genes , Terapia Genética/métodos , Infarto do Miocárdio/terapia , Função Ventricular Esquerda/fisiologia , Animais , Eletroporação , Humanos , Proteínas com Domínio MARVEL , Masculino , Infarto do Miocárdio/genética , Infarto do Miocárdio/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica
19.
Zhonghua Xin Xue Guan Bing Za Zhi ; 35(4): 340-3, 2007 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-17711661

RESUMO

OBJECTIVE: To analyze the clinical features and outcomes of patients with immunoglobulin light-chain amyloidosis (AL) who had heart involvement. METHODS: Clinical features and outcomes of AL amyloidosis patients with heart involvement in the past 7 years in our hospital were retrospectively analyzed. RESULTS: Cardiac involvement was seen in 36 out of the 60 AL patients (60%). The clinical manifestations of cardiac amyloidosis included heart failure (50%), low QRS voltage (47.2%) and pseudomyocardial infarction (33.3%) in electrocardiography, as well as thickening of ventricular wall (63.9%), echo of granular sparkling texture (11.1%), atria dilation (33.3%) and diastolic dysfunction (30.6%) in echocardiography. The prognosis was poor, with a median survival time of 13.9 months. CONCLUSION: Patients of AL amyloidosis with cardiac involvement are not rare. Thickening of ventricular wall and diastolic dysfunction are the most common characteristics. Special attention should be paid to this disease.


Assuntos
Amiloidose/diagnóstico , Amiloidose/patologia , Cardiomiopatias/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatias/diagnóstico , Feminino , Humanos , Cadeias Leves de Imunoglobulina , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
20.
Zhonghua Nei Ke Za Zhi ; 46(2): 107-10, 2007 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-17445432

RESUMO

OBJECTIVE: To compare the short-term efficacy and safety of high loading dose (600 mg) clopidogrel treatment with those of routine loading dose (300 mg) in patients with acute coronary syndrome and provide evidence for planning clopidogrel treatment. METHODS: 60 patients were randomized into two groups, One group received 300 mg loading dose clopidogrel, while the other received 600 mg and both were followed by 75 mg daily thereafter. Adenosine diphosphate (ADP) (5 micromol/L and 20 micromol/L) induced platelet aggregation was examined at baseline (before administration), 2 hours and 6 hours after administration and the count of white blood cell and platelet 3 days after loading dose. The primary end points were hemorrhagic events, granulocytopenia and thrombocytopenia within 3 days after administration. RESULTS: With a high-dose agonist (20 micromol/L ADP), loading doses of clopidogrel at 300 mg and 600 mg both produced greater inhibition of baseline ADP (20 micromol/L) induced aggregation 6 hours after administration than 2 hours [group of 300 mg: (29.75+/-12.11)% vs (43.63+/-14.31)%, P<0.05. Group of 600 mg: (28.86+/-10.24)% vs (34.86+/-10.84)%, P<0.05]. Treatment with clopidogrel at 600 mg loading dose had a marked earlier effect on platelet aggregation 2 hours after administration than that of 300 mg [(34.86+/-10.84)% vs (43.63+/-14.31)%, P<0.05]. The platelet aggregation of the two groups tended towards similar at 6 hours after the procedure [(28.86+/-10.24)% vs (29.75+/-12.11)%, P>0.05]. There were no episodes of hemorrhagic events, granulocytopenia and thrombocytopenia within 3 days after the procedure. CONCLUSIONS: In Chinese patients with acute coronary syndrome platelet aggregation can be inhibited more rapidly and more effectively with clopidogrel at 600 mg loading dose when compared with that at 300 mg loading dose and the safety aspect between the two different loading doses is equivalent.


Assuntos
Angina Instável/sangue , Infarto do Miocárdio/sangue , Agregação Plaquetária/efeitos dos fármacos , Ticlopidina/análogos & derivados , Adulto , Idoso , Angina Instável/tratamento farmacológico , Clopidogrel , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Ticlopidina/efeitos adversos , Ticlopidina/farmacologia
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