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1.
Cell Prolif ; : e12827, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32406154

RESUMO

OBJECTIVES: Previously, we found that by regulating T helper (Th) cell polarization, calcitriol intervention inhibited lipopolysaccharide (LPS)-induced alveolar bone loss in an animal periodontitis model, but the underlying cellular events remain unknown. MATERIALS AND METHODS: In this study, mouse Th cells were incubated in an inflammatory environment in the presence of dendritic cells (DCs) and LPS. Then, the potential of the Th cells to undergo Th2/Th17 polarization, the RANKL expression of the polarized Th cells and the subsequent influences of the polarized Th cells on RAW264.7 cell osteoclastogenesis in response to calcitriol administration were assessed. Finally, the effects of calcitriol on antigen presentation by DCs during these cellular events were evaluated. RESULTS: In response to calcitriol administration, Th cells in an inflammatory environment exhibited an enhanced potential for Th2 polarization along with a decreased potential for Th17 polarization. In addition, RANKL expression in Th17-polarized cells was largely inhibited. Furthermore, inflammation-induced osteoclastogenesis in RAW264.7 cells was suppressed following coculture with calcitriol-treated Th cells. During these cellular events, increased expression of Th2 promoters (such as OX-40L and CCL17) and decreased expression of Th17 promoters (such as IL-23 and IL-6) were found in DCs. CONCLUSIONS: Calcitriol can inhibit osteoclastogenesis in an inflammatory environment by changing the proportion and function of Th cell subsets. Our findings suggest that calcitriol may be an effective therapeutic agent for treating periodontitis.

2.
J Am Chem Soc ; 142(16): 7497-7505, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32223234

RESUMO

A water-soluble probe, TPA-1OH, with aggregation-induced emission activity is synthesized and used for expedient real-time fluorescence in situ visualization of latent fingerprints (LFPs). A TPA-1OH aqueous solution exhibits nonfluorescence in pure water while strong fluorescence upon molecular aggregation induced by addition of poor solvent. Fluorescence images of LFPs on a variety of substrates, including rough surfaces such as walls, bricks, and paper, are developed under 405 nm light, by soaking in or spraying with a TPA-1OH aqueous solution (30 µM) without any necessity of organic cosolvents and post-treatment steps. The probe is noncytotoxic at a concentration lower than 50 µM. The development process of LFPs is demonstrated by real-time fluorescence in situ imaging. The exponential relationship between the relative fluorescence intensity and time is deduced from the fitting curve. The LFP images developed by TPA-1OH are evident and intact enough to allow that the level 1-3 details are displayed and analyzed. Noteworthily, the level 3 details of LFPs such as the fingerprint ridge width and the characteristics of the sweat pores are evidently visible under fluorescence microscopy. Even the nanoscopic details exceeding level 3 are visualized under super-resolution microscopy with sub-50 nm optical resolution.

4.
Medicine (Baltimore) ; 99(11): e19244, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176048

RESUMO

A mutation in the epithelial morphogen gene ectodysplasin-A1 (EDA1) is responsible for the disorder X-linked hypohidrotic ectodermal dysplasia (XLHED), the most common form of ectodermal dysplasia. XLHED is characterized by impaired development of hair, eccrine sweat glands, and teeth. This study aimed to identify potentially pathogenic mutations in four Chinese XLHED families.Genomic DNA was extracted from the peripheral blood and sequenced. Sanger sequencing was used to carry out mutational analysis of the EDA1 gene, and the three-dimensional structure of the novel mutant residues in the EDA trimer was determined. Transcriptional activity of NF-κB was tested by Dual luciferin assay.We identified a novel EDA1 mutation (c.1046C>T) and detected 3 other previously-reported mutations (c.146T>A; c.457C>T; c.467G>A). Our findings demonstrated that novel mutation c.1046C>T (p.A349 V) resulted in XLHED. The novel mutation could cause volume repulsion in the protein due to enlargement of the amino acid side chain. Dual luciferase assay revealed that transcriptional NF-κB activation induced by XLHED EDA1 protein was significantly reduced compared with wild-type EDA1.These results extend the spectrum of EDA1 mutations in XLHED patients and suggest a functional role of the novel mutation in XLHED.


Assuntos
Displasia Ectodérmica Anidrótica Tipo 1/etnologia , Displasia Ectodérmica Anidrótica Tipo 1/genética , Ectodisplasinas/genética , Predisposição Genética para Doença , Luciferases/genética , Mutação de Sentido Incorreto/genética , Pré-Escolar , China , Displasia Ectodérmica Anidrótica Tipo 1/fisiopatologia , Feminino , Humanos , Masculino , Linhagem , Reação em Cadeia da Polimerase/métodos
5.
Oral Dis ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32104948

RESUMO

OBJECTIVE: The aim of this study was to determine how the removal of non-impacted third molars (N-M3s) affects the periodontal status of neighboring second molars (M2s). SUBJECTS AND METHODS: The periodontal condition of M2s for which the neighboring N-M3s were removed (more than 6 months previously) and those with intact N-M3s was analyzed in a cross-sectional observation study. In an additional case series, periodontal changes in M2s in response to adjacent N-M3 removal were observed during a 6-month follow-up period. RESULTS: A total of 457 patients with 1,301 M2s were enrolled in this cross-sectional observational study. Compared to M2s with neighboring N-M3s, M2s without neighboring N-M3s (teeth removed more than 6 months previously) exhibited a 0.27-mm reduction in the average pocket depth (PD) (p < .001) and a 0.38-fold reduced risk of at least one probing site with PD ≥5 mm (PD5+) (p < .001). Subsequently, a 41-case follow-up study showed that 6 months after neighboring N-M3 extraction, the PD of the M2s decreased by 0.31 mm (p < .001), while the incidence of PD5+ decreased by 21.9% when compared to the parameters detected before tooth extraction (p = .004). CONCLUSIONS: Removing N-M3s was associated with an improved periodontal condition in neighboring M2s.

6.
Reprod Sci ; 27(6): 1276-1284, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32046461

RESUMO

In response to cytosolic DNA, stimulator of interferon gene (STING) initiates and orchestrates host's innate immunity by inducing type I interferon. Since endometriosis is a chronic inflammatory disorder, we sought to determine whether STING pathway is activated in ectopic endometrium in comparison to eutopic endometrium. Immunohistochemistry was employed in evaluating the expression levels of STING in normal endometrium, endometriosis, and adenomyosis. The density of CD45+ intraepithelial lymphocytes was correlated with STING expression levels. A total of 39 cases of endometriosis and/or adenomyosis with normal endometrium were analyzed. Among them, 32 had adenomyosis, 26 had endometriosis, and 19 have both lesions. STING protein expression is mainly evident in the cytoplasm of epithelial cells but much less in stromal cells. Based on H-score, we found that the STING expression levels were significantly higher in the epithelial cells of adenomyosis and endometriosis than in eutopic endometrium (132.7 ± 12.20, 119.6 ± 12.57 vs. 19.74 ± 5.96, p < 0.0001). There was no significant difference in STING expression level between endometriosis and adenomyosis. More intraepithelial lymphocytes were detected in endometriosis and adenomyosis lesions than endometrium (5.60 ± 0.70%, 4.95 ± 0.54% vs. 1.25 ± 0.12%, p < 0.0001). A positive correlation between STING expression and intraepithelial lymphocytic infiltrate was observed (p < 0.0001). In summary, STING was upregulated in the epithelium of ectopic endometrium as compared to eutopic endometrium. Its expression levels correlate with the degree of intraepithelial lymphocyte infiltration, suggesting a role in promoting chronic inflammation of ectopic endometrium.

7.
J Cardiothorac Surg ; 15(1): 38, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32087712

RESUMO

BACKGROUND: Patients with DeBakey type II aortic dissection or ascending aortic aneurysms involving the right innominate artery require hemiarch replacement and placement of a right innominate artery graft. Traditional aortic hemiarch replacement surgery must be performed under right axillary artery cannulation perfusion and moderate or deep hypothermia circulatory arrest. However, the axillary artery perfusion is always associated with left subclavian artery "steal blood", and it cannot guarantee blood supply to the left cerebral hemisphere in patients with an incomplete circle of Willis, and hypothermia and hypoperfusion cause damage to the brain and spinal cord; therefore, postoperative complications of the nervous system are common. Herein, we present a hemiarch replacement procedure with the use of the single branch-first combined with the mid-arch clamping technique. This procedure can not only reduce the axillary artery incision but also eliminate the need for mid-deep hypothermia and circulatory arrest. CASE PRESENTATION: A 41-year-old male patient underwent surgery with this technique. Computed tomography angiography performed upon admission showed calcified plaques scattered throughout the aorta and showed DeBakey type II aortic dissection involving the right innominate artery, accompanied by cardiac tamponade. The patient underwent aortic root repair, ascending aorta replacement, and hemiarch replacement as well as the placement of a right innominate artery graft. Aortic root anastomosis was performed with the embedded anastomosis technique. There were no postoperative complications. The patient was discharged 11 days after the operation. During more than 3 months of follow-up, there were no cases of aortic valve regurgitation or anastomotic fistula. CONCLUSIONS: The single branch-first combined with the mid-arch clamping technique for the right innominate artery can reduce the axillary artery incision and avoid damage to the body under mid-deep hypothermia and circulatory arrest. The embedded anastomosis technique is easy to perform, results in a limited amount of bleeding and requires almost no extra needling. We believe that these techniques can serve as good alternative strategies for patients with DeBakey type II aortic dissection or ascending aortic aneurysms involving the right innominate artery.

8.
J Cardiothorac Surg ; 14(1): 184, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684975

RESUMO

BACKGROUND: Traditional aortic arch replacement surgery must be performed under moderate or deep hypothermia (22-28 °C) and circulatory arrest. Hypothermia and hypoperfusion can cause damage to the nervous system; therefore, postoperative brain and spinal cord complications are common. Improvements in surgical techniques are necessary to solve this problem. Herein, we report a method of total aortic arch replacement that can be performed at a core temperature of 34 °C, similar to other simple cardiac operations. CASE PRESENTATION: Four patients underwent surgery with this technique (3 males and 1 female, aged 48 to 67 years). Computed tomography angiography performed at admission showed a total aortic dissection, resulting in a diagnosis of Stanford type A aortic dissection. The patients underwent emergency aortic sinus remodelling, ascending aortic replacement, modified aortic arch replacement, and elephant trunk stenting. No patients had neurological complications. During a follow-up of more than 1-month, no patients had aortic valve regurgitation or anastomotic leak. CONCLUSIONS: This technique can increase the operating temperature by approximately 6 to 12 °C and reduce the circulatory arrest time by approximately 18 to 28 min. All of the patients recovered well without any neurological complications, demonstrating the feasibility and safety of this technique. We believe that this technique can serve as a good alternative strategy for managing aortic dissection and aneurysm, especially for young surgeons who are acquiring experience in arch replacement surgery.


Assuntos
Aneurisma Dissecante/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Idoso , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico por imagem , Implante de Prótese Vascular , Temperatura Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Stents , Tomografia Computadorizada por Raios X , Procedimentos Cirúrgicos Vasculares/métodos
9.
Drug Des Devel Ther ; 13: 3391-3404, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576113

RESUMO

Purpose: It has been reported that approximately 40% of ALI (acute lung injury) incidence resulted from sepsis. Paclitaxel, as a classic anti-cancer drug, plays an important role in the regulation of inflammation. However, we do not know whether it has a protective effect against CLP (cecal ligation and puncture)-induced septic ALI. Our study aims to illuminate the mitigative effects of paclitaxel on sepsis-induced ALI and its relevant mechanisms. Materials and methods: The survival rates and organ injuries were used to evaluate the effects of paclitaxel on CLP mice. The levels of inflammatory cytokines were tested by ELISA. MUC1 siRNA pre-treatment was used to knockdown MUC1 expression in vitro. GO203 was used to inhibit the homodimerization of MUC1-C in vivo. The expression levels of MUC1, TLR 4 and p-NF-κB/p65 were detected by Western blot. Results: Our results showed that paclitaxel improved the survival rates and ameliorated organ injuries especially lung injury in CLP-induced septic mice. These were accompanied by reduced inflammatory cytokines in sera and BALF (bronchoalveolar lavage fluid). We also found paclitaxel could attenuate TLR 4-NF-κB/p65 activation both in lung tissues of septic mice and LPS-stimulated lung type II epithelial cell line A549. At the upstream level, paclitaxel-upregulated expression levels of MUC1 in both in vivo and in vitro experiments. The inhibitory effects of paclitaxel on TLR 4-NF-κB/p65 activation were reversed in lung tissues of septic mice pre-treated with MUC1 inhibitor and in MUC1-knockdown A549 cells. Protection of paclitaxel on sepsis-induced ALI and decrease of inflammatory cytokines were also abolished by inhibition of MUC1. Conclusion: Collectively, these results indicated paclitaxel could significantly alleviate acute lung injury in CLP-induced septic mice and LPS-stimulated lung type II epithelial cell line A549 by activating MUC1 and suppressing TLR-4/NF-κB pathway.

10.
Cancer Med ; 8(15): 6549-6558, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31502764

RESUMO

To investigate the incidence and risk factors as well as prognosis of autoimmune hemolytic anemia (AIHA) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), a total of 1377 adult hematological malignancies at three institutions were enrolled in this study. The 3-year cumulative incidence of AIHA was 2.2 ± 0.4%. Multivariate analysis showed that haploidentical donors (HRDs) and chronic graft vs host disease (cGVHD) were the independent risk factors for AIHA. Patients with AIHA treated initially with corticosteroids combined with cyclosporine A (CsA) had a higher complete response rate than those with corticosteroids monotherapy (66.7% vs 11.1%; P = .013). The 3-year cumulative incidence of malignant diseases relapse was 4.4 ± 4.3% and 28.0 ± 1.3% (P = .013), treatment-related mortality (TRM) was 8.9 ± 6.3% and 17.4 ± 1.2% (P = .431), disease-free survival (DFS) was 56.1 ± 1.5% and 86.7 ± 7.2% (P = .011), and overall survival (OS) was 86.3 ± 7.4% and 64.1 ± 1.5% (P = .054), respectively, in the patients with AIHA and those without AIHA. Our results indicate that HRDs and cGVHD are risk factors for AIHA and corticosteroids combined with CsA are superior to corticosteroids as initial treatment for AIHA. Autoimmune hemolytic anemia does not contribute to increase TRM and could reduce the malignant diseases relapse and increase DFS.

11.
Neural Netw ; 119: 151-161, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31446234

RESUMO

Transfer learning has achieved a lot of success in deep neural networks to reuse useful knowledge from source domains. However, most of the existing transfer learning strategies on neural networks are for classification tasks or based on simple training strategies, which have limited use in multi-source knowledge regression due to the ineffectiveness of learning common latent features and source information loss in regression. In this paper, we propose transferable Recurrent Neural Network (RNN) units on the Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU) to adapt source knowledge in multi-source regression scenarios. Specifically, two knowledge adaptation methods are proposed, the first one utilizes similarity weights as the transfer coefficients of each source, and the other defines a transfer-gate to control the flow of source knowledge. By using the proposed methods, useful source knowledge embedded in both internal state and output is adapted. Extensive experiments on both synthetic data and human motion prediction tasks on the Human 3.6M dataset demonstrate the superiority of our transfer RNN units compared with conventional models.


Assuntos
Aprendizado Profundo , Humanos
12.
Front Neurosci ; 13: 559, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244594

RESUMO

Neural circuits respond to multiple sensory stimuli by firing precisely timed spikes. Inspired by this phenomenon, the spike timing-based spiking neural networks (SNNs) are proposed to process and memorize the spatiotemporal spike patterns. However, the response speed and accuracy of the existing learning algorithms of SNNs are still lacking compared to the human brain. To further improve the performance of learning precisely timed spikes, we propose a new weight updating mechanism which always adjusts the synaptic weights at the first wrong output spike time. The proposed learning algorithm can accurately adjust the synaptic weights that contribute to the membrane potential of desired and non-desired firing time. Experimental results demonstrate that the proposed algorithm shows higher accuracy, better robustness, and less computational resources compared with the remote supervised method (ReSuMe) and the spike pattern association neuron (SPAN), which are classic sequence learning algorithms. In addition, the SNN-based computational model equipped with the proposed learning method achieves better recognition results in speech recognition task compared with other bio-inspired baseline systems.

14.
J Periodontal Res ; 54(6): 612-623, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31095745

RESUMO

BACKGROUND: Although the immunomodulatory properties of calcitriol in bone metabolism have been documented for decades, its therapeutic role in the management of periodontitis remains largely unexplored. In this study, we hypothesized that calcitriol suppresses lipopolysaccharide (LPS)-induced alveolar bone loss by regulating T helper (Th) cell subset polarization. METHODS: To test this hypothesis, we determined the effect of calcitriol intervention on the development of LPS-induced periodontitis in rats in terms of bone loss (micro-CT analysis), local inflammatory infiltration levels, the number of osteoclasts (hematoxylin and eosin staining) and the level of osteoclastogenesis (tartrate-resistant acid phosphatase method). Furthermore, immunohistochemistry was used to assess the expression levels of the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) as well as the cytokine levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-17, and IL-10 throughout the LPS-injected region. Finally, the polarization potential of Th cells in peripheral blood was analyzed using flow cytometry. RESULTS: Calcitriol intervention decreased alveolar bone loss in response to LPS injection and inflammatory cell infiltration. Analysis of osteoclast number and RANKL and OPG expression showed that bone resorption activity was largely suppressed in response to calcitriol administration, along with decreased IL-17 levels but increased IL-4 and IL-10 levels in periodontal tissues (the LPS-injected region). Similarly, the percentages of Th2 and Treg cells in peripheral blood increased, but the percentages of Th1 and Th17 cells decreased in rats receiving calcitriol. CONCLUSION: Our findings suggest that calcitriol can be used to inhibit bone loss in experimental periodontitis, likely via the regulation of local and systemic Th cell polarization.


Assuntos
Perda do Osso Alveolar/prevenção & controle , Calcitriol/farmacologia , Periodontite/tratamento farmacológico , Linfócitos T Auxiliares-Indutores/citologia , Perda do Osso Alveolar/imunologia , Animais , Citocinas/imunologia , Lipopolissacarídeos , Masculino , Osteoclastos , Osteogênese , Osteoprotegerina/metabolismo , Periodontite/induzido quimicamente , Ligante RANK/metabolismo , Ratos , Ratos Sprague-Dawley , Linfócitos T Auxiliares-Indutores/imunologia
15.
PLoS One ; 14(4): e0216082, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31022256

RESUMO

The elicitor Hrip1 isolated from necrotrophic fungus Alternaria tenuissima, could induce systemic acquired resistance in tobacco to enhance resistance to tobacco mosaic virus. In the present study, we found that the transgenic lines of Hrip1-overexpression in wild type (WT) Arabidopsis thaliana were more resistant to Spodoptera exigua and were early bolting and flowering than the WT. A profiling of transcription assay using digital gene expression profiling was used for transgenic and WT Arabidopsis thaliana. Differentially expressed genes including 40 upregulated and three downregulated genes were identified. In transgenic lines of Hrip1-overexpression, three genes related to jasmonate (JA) biosynthesis were significantly upregulated, and the JA level was found to be higher than WT. Two GDSL family members (GLIP1 and GLIP4) and pathogen-related gene, which participated in pathogen defense action, were upregulated in the transgenic line of Hrip1-overexpression. Thus, Hrip1 is involved in affecting the flower bolting time and regulating endogenous JA biosynthesis and regulatory network to enhance resistance to insect.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/parasitologia , Resistência à Doença , Flores/fisiologia , Doenças das Plantas/imunologia , Doenças das Plantas/parasitologia , Spodoptera/fisiologia , Animais , Arabidopsis/imunologia , Proteínas de Arabidopsis/genética , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas , Oxilipinas/metabolismo , Fotoperíodo , Plantas Geneticamente Modificadas , Reprodutibilidade dos Testes
16.
Arch Oral Biol ; 101: 100-107, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30913450

RESUMO

OBJECTIVE: To explore the gene mutation in an incontinentia pigmenti (IP) patient with syndromic tooth agenesis. METHODS: Long-range polymerase chain reaction (PCR) and Sanger sequencing were used to detect inhibitor of nuclear factor kappa-B kinase subunit gamma (IKBKG) mutation in the IP patient. We used the nuclear factor kappa B (NF-κB) reporter gene to assess activation of NF-κB, after transfecting an empty vector, wild-type, or mutant NF-κB essential modulator (NEMO) plasmid into IKBKG-deficient HEK293T cells, respectively. Furthermore, we performed immunoprecipitation and immunoblotting to describe the polyubiquitination of NEMO. Lastly, we detected the interactions between mutant NEMO and I kappa B kinase alpha (IKKα), I kappa B kinase beta (IKKß), TNF receptor associated factor 6 (TRAF6), HOIL-1-interacting protein (HOIP), hemo-oxidized iron regulatory protein 2 ligase 1 (HOIL-1), and SHANK-associated RH domain interactor (SHARPIN). RESULTS: A de novo nonsense mutation in IKBKG (c.924C > G; p.Tyr308*) was observed. The Tyr308* mutation inhibited activation of the NF-κB pathway by reducing K63-linked polyubiquitination and linear polyubiquitination. The mutant NEMO was not able to interact with TRAF6, HOIL-1, or SHARPIN. CONCLUSIONS: We identified a novel nonsense IKBKG mutation (c.924C > G; p.Tyr308*) in an IP patient with syndromic tooth agenesis. This research enriches the mutation spectrum of the IKBKG gene.


Assuntos
Anodontia/genética , Quinase I-kappa B/genética , Incontinência Pigmentar/genética , Mutação , Genes Reporter , Células HEK293 , Humanos , NF-kappa B/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Ubiquitinas/metabolismo
17.
J Org Chem ; 84(7): 4095-4103, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30808174

RESUMO

Intramolecular imino-ene reaction of 2 H-aziridine has been studied experimentally and computationally, demonstrating that (1) the concerted process takes place regioselectively on the alkene E-CH group; (2) the geometry of the N-linker impacts the reaction activation energy and diastereoselectivity significantly, with pyramidal alkyl amine as the linkage, an exclusive cis-product is achieved; (3) when the reaction has to occur with the Z-CH group, the cis-diastereoselectivity is solely observed regardless of the nature of the N-linkage.

18.
Cardiovasc Revasc Med ; 20(12): 1158-1164, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30755362

RESUMO

BACKGROUND: Differences in the predictors between ventricular septal rupture (VSR) and free wall rupture (FWR) have not been fully studied. Data on the prevalence and clinical outcome of heart rupture are limited. HYPOTHESIS: This study aimed to investigate heart rupture incidence and clinical results in patients with acute myocardial infarction (AMI). METHODS: Of 9265 AMI patients in the MOODY registry between March 1999 and October 2016, a total of 146 were studied. The primary clinical endpoint was rupture prevalence and in-hospital mortality. Independent factors of heart rupture were analyzed using Cox proportional model and were compared between patients with VSR and those with FWR. RESULTS: Of 9265 AMI patients, 146 (1.58%) patients had a heart rupture (FWR, 94 (1.02%)) and VSR (52 (0.56%)). All patients with FWR died during hospitalization, and in-hospital mortality was recorded in 37 (71.2%) patients with VSR, who had an extremely longer time delay from AMI onset to the first medical contact (FMC) (~20 h). FWR usually occurred in patients with ST-elevation myocardial infarction (STEMI) patients with a FMC ≥ 3 h, for whom primary reperfusion was not performed. Percutaneous repair at 1-2 weeks following AMI was associated with less mortality, and 9 of 38 patients who underwent non-primary reperfusion died post procedure. CONCLUSION: This study demonstrated the importance of shortening FMC to prevent VSR and of early primary reperfusion in STEMI patients to reduce FWR. Urgent closure of rupture is necessary to reduce in-hospital and 1-year mortality. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.org, identifier: No. NCT03051048.

19.
Org Biomol Chem ; 17(6): 1542-1546, 2019 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-30681111

RESUMO

A copper catalyzed intramolecular 1,2-carboboration of o-aldiminyl cinnamate has been realized in both regio- and stereoselective fashions. This reaction provides a convenient entry to highly valuable and otherwise challenging cis-2,3,4-trisubstituted tetrahydroquinolines carrying a 4-boryl group. An unusual non-Michael addition intermediate or alternatively, a cyclic enolate is proposed to account for the intriguing all-cis configuration in the final products.

20.
J Org Chem ; 84(5): 2721-2731, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30695635

RESUMO

In this study, we performed a theoretical investigation of the intramolecular cyclization of bicyclic 2-allyl-2-methyl-2,3-dihydro-1 H-inden-1-iminyl radical 1 along with several iminyl model compounds. The results were used to comparatively evaluate the reaction mechanism suggested previously, in which the neophyl-like rearrangement was deemed to play a decisive role. The present computation and numerical simulation identify the experimentally observed endo product in the high-temperature cyclization of 1. The product results from a kinetically controlled endo cyclization-reduction pathway involving an initial reversible 5- exo ring-closure/ring-opening process, not via 5- exo cyclization/neophyl-like rearrangement/ endo-radical reduction pathway as proposed previously. Considering many available theoretical and experimental results, the neophyl-like rearrangement seems to play only a minor role in the intramolecular cyclization of N- and C-centered radicals. The structural effect of cyclized radical intermediates of bicyclic 1 leads to a lower thermodynamic reaction energy of exo cyclization than of endo cyclization, which together with the temperature effect should be responsible for the formation of the dominant endo product in the high-temperature region. Additionally, this investigation provided further insight into the cyclization of 1 and compounds structurally similar to 1; that is, control of endo- or exo-regioselective products is readily available by regulating the reaction temperature.

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