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1.
Biochem Biophys Res Commun ; 521(4): 997-1002, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31727364

RESUMO

Laccases (benzenediol: oxygen oxidoreductases, EC1.10.3.2) can oxidize various substrates, and those which are tolerant to and even activated by salts have attracted a lot of attention due to their application potential in certain industries. The mechanism of the salt activation of laccases is awaiting to be elucidated yet. Our previous study (Li, Xie et al. 2018) supposed that the salt activation of marine laccase Lac15 might be attributed to Cl- ion specifically binding to some local sites to interfere substrate binding and/or electron transfer. In this study, we found two sites whose mutations resulted in elimination of the salt activation of Lac15's activity towards catechol and dopamine respectively, and revealed that the mutations affected the activity by altering both Em and kcat, demonstrating the supposed mechanism. A model for the salt activation of laccases was accordingly proposed, albeit some details are to be elucidated.

2.
Med Sci Monit ; 25: 9103-9111, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31785094

RESUMO

BACKGROUND In this study, we investigated the clinical and pathological features of patients with lipid storage myopathy (LSM) complicated with hyperuricemia, to improve clinicians' understanding of metabolic multi-muscular disorder with metabolic disorders, and to reduce the risk of missed diagnosis of LSM. MATERIAL AND METHODS From January 2005 to December 2017, 8 patients underwent muscle biopsy and diagnosed by muscle pathology and genetic testing in our hospital. All 8 patients were in compliance with LSM diagnosis. We collected data on the patient's clinical performance, adjuvant examination, treatment, and outcomes to provide a comprehensive report and description of LSM patients with hyperuricemia. RESULTS All patients were diagnosed as having ETFDH gene mutations. The main clinical manifestations of patients were chronic limb and trunk weakness, limb numbness, and muscle pain. The serum creatine kinase (CK) values in all patients were higher than normal values. Electromyography showed 3 cases of simple myogenic damage and 3 cases of neurogenic injury. Hematuria metabolic screening showed that 2 patients had elevated glutaric aciduria, and 1 patient had elevated fatty acyl carnitine in the blood. All patients were given riboflavin treatment, and the clinical symptoms were significantly improved, and 3 patients returned to normal uric acid levels after treatment. Pathological staining showed an abnormal deposition of lipid droplets in muscle fibers. CONCLUSIONS If an adolescent hyperuricemia patient has abnormal limb weakness, exercise intolerance, and elevated serum CK values, clinicians need to be highly alert to the possibility of LSM. Early diagnosis and treatment of LSM should improve the clinical symptoms and quality of life and reduce complications.

3.
Medicine (Baltimore) ; 98(51): e18070, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860956

RESUMO

INTRODUCTION: In this study, we presented a rare case of Epstein-Barr virus (EBV) meningoencephalitis presented with meningoencephalitis-like symptoms and diffuse edematous hemorrhage. PATIENT CONCERNS: A 77-year-old male patient was admitted to our hospital with fever, headache, confusion, and unconsciousness for 7 days. Physical examination revealed unconsciousness and stiffness of the neck. DIAGNOSIS: The final diagnosis was EBV meningoencephalitis. INTERVENTIONS: Ganciclovir (two times 350 mg/day, 21 days), methylprednisolone sodium succinate (120 mg, 5 days), and IV immunoglobulins (IV Ig) (0.4 g/kg, 5 days) were given to this patient. OUTCOMES: But the patient's clinical symptoms did not improve, and he was still in a coma. His family refused to be further diagnosed and discharged. After discharge for 2 months, the patient was in a coma. Four months later, the patient died of complications of pulmonary infection. CONCLUSION: The patient is an adult, and imaging was dominated by intracranial diffuse microhemorrhage and edema, which was different from the typical imaging characteristics of EBV encephalitis as previously reported. This specific imaging change may provide new clinical value for the diagnosis of EBV encephalitis.


Assuntos
Infecções por Vírus Epstein-Barr/tratamento farmacológico , Ganciclovir/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Imagem por Ressonância Magnética/métodos , Meningoencefalite/tratamento farmacológico , Metilprednisolona/administração & dosagem , Idoso , Quimioterapia Combinada , Infecções por Vírus Epstein-Barr/diagnóstico por imagem , Seguimentos , Humanos , Masculino , Meningoencefalite/diagnóstico por imagem , Meningoencefalite/virologia , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
4.
Int J Neurosci ; : 1-5, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31694440

RESUMO

Background: To our knowledge, this is the first report of patient with BHD syndrome caused by a novel mutation in the FLCN gene who developed a cerebral venous sinus thrombosis(CVST).Case presentation: A 62-year-old male patient with a history of hypertension and two case of spontaneous pneumothorax. He had a 1-month history of headache and was admitted to the hospital one day after the headache aggravated. The patient had a family history of BHD syndrome which was confirmed by FLCN gene sequencing. Sequencing analysis revealed a novel nonsense mutation (NM_144997; c.607A > T; p.Lys203Ter) in the FLCN gene exon 6 of the patient, which was proved to be a pathogenetic mutation by pedigree verification. BHD syndrome was finally definitive diagnosis. Low molecular weight heparin (21 days) was given for anticoagulant therapy before and after resection of renal tumor which is confirmed to be clear cell carcinoma in the kidney. After discharge, warfarin was given for anticoagulant therapy (6 months).Conclusions: There was no recurrence of CVST. And no recurrence of tumor and new renal tumor were found in renal MRI examination after 6 months.

5.
Biochem Biophys Res Commun ; 519(4): 894-900, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31563321

RESUMO

Laccases (benzenediol: oxygen oxidoreductases, EC1.10.3.2) can oxidize wide range of compounds thus have great application potential in diverse industries. The catalytic mechanisms of laccases have been extensively studied, while the details of proton transfer remain to be fully elucidated. In this study, we tried to uncover the sites that are crucial for the proton transfer of microbial laccase Lac15. A residue near the trinuclear copper center, D396, was indicated by statistical coupling analysis (SCA) and structural alignment to be an important site like D93, which is conserved in laccases and believed crucial for the catalysis by facilitating proton transfer. A representative mutant at this site, D396A, similar to D93A, exhibited significantly impaired catalysis with the global structure and substrate binding slightly perturbed. The mutation resulted in stay of the intermediate I, which would accept a proton to proceed to next catalysis stage, suggesting D396 might play a critical role in the proton transfer. Our finding may help to completely elucidate the proton transfer mechanism in laccases.

6.
J Zhejiang Univ Sci B ; 20(5): 428-436, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31090268

RESUMO

Hyaluronan is a widely occurring extracellular matrix molecule, which is not only a supporting structural component, but also an active regulator of cellular functions. The chemophysical and biological properties of hyaluronan are greatly affected by its molecular size and several hyaluronan-binding proteins, making hyaluronan a fascinating molecule with great functional diversity. This review summarizes our current understanding of the roles of hyaluronan in cardiovascular and nervous system disorders, such as atherosclerosis, myocardial infarction, and stroke, with the aim to provide a foundation for future research and clinical trials.


Assuntos
Doenças Cardiovasculares/metabolismo , Ácido Hialurônico/fisiologia , Doenças do Sistema Nervoso/metabolismo , Envelhecimento , Animais , Aterosclerose/metabolismo , Aterosclerose/fisiopatologia , Biomarcadores/metabolismo , Encéfalo/fisiopatologia , Movimento Celular , Matriz Extracelular/metabolismo , Coração/embriologia , Coração/fisiopatologia , Humanos , Esclerose Múltipla/fisiopatologia , Infarto do Miocárdio/metabolismo , Ligação Proteica , Convulsões/fisiopatologia , Transdução de Sinais , Traumatismos da Medula Espinal/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia
7.
J Neuroinflammation ; 16(1): 72, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953513

RESUMO

BACKGROUND: Diabetes is known to be a main risk factor of post-stroke hemorrhagic transformation following recombinant tissue plasminogen activator (rt-PA) therapy. However, the mechanism through which diabetes exacerbates hemorrhagic transformation is insufficiently understood. We aimed to verify that CD147, the extracellular matrix metalloproteinase (MMP) inducer, played a vital role in the progress. METHODS: We performed middle cerebral artery occlusion on diabetic and non-diabetic rats, with or without rt-PA treatment, and then compared the glycosylation level of CD147, caveolin-1, MMPs activities, and blood-brain barrier (BBB) permeability. In vitro, tunicamycin treatment and genetic tools were used to produce non-glycosylated and lowly glycosylated CD147. An endogenous glucagon-like peptide-1 receptor (GLP-1R) agonist was used to downregulate the glycosylation of CD147 in vivo. RESULTS: Compared with non-diabetic rats, diabetic rats expressed higher levels of highly glycosylated CD147 in endothelium and astrocytes following rt-PA treatment accompanied by higher activity of MMPs and BBB permeability, in the middle cerebral artery occlusion model. Caveolin-1 was also overexpressed and co-localized with CD147 in astrocytes and endothelium in diabetic rats. In vitro, advanced glycation end products increased the expression of highly glycosylated CD147 in astrocytes and endothelial cells. Downregulating the glycosylation of CD147 lowered the activity of MMPs and promoted the expression of tight junction proteins. The expression of caveolin-1 in endothelial cells and astrocytes was not inhibited by tunicamycin, which revealed that caveolin-1 was an upstream of CD147. In vivo, GLP-1R agonist downregulated the glycosylation of CD147 and further reduced the activity of MMPs and protected the BBB in diabetic rats. CONCLUSION: CD147 is essential for diabetes-associated rt-PA-induced hemorrhagic transformation, and downregulation of CD147 glycosylation is a promising therapy for neurovascular-unit repair after rt-PA treatment of patients with diabetes.


Assuntos
Basigina/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Hemorragia/etiologia , Infarto da Artéria Cerebral Média/complicações , Ativador de Plasminogênio Tecidual/efeitos adversos , Animais , Astrócitos/efeitos dos fármacos , Barreira Hematoencefálica/fisiopatologia , Encéfalo/citologia , Caveolina 1/genética , Caveolina 1/metabolismo , Células Cultivadas , Colágeno Tipo IV/metabolismo , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Glicosilação/efeitos dos fármacos , Infarto da Artéria Cerebral Média/patologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Ocludina/metabolismo , RNA Interferente Pequeno/genética , Ratos , Ratos Wistar , Reperfusão
8.
J Int Med Res ; 47(5): 2256-2261, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30880528

RESUMO

Varicella zoster virus (VZV) can invade the brainstem or brain via the glossopharyngeal, vagus , or facial nerve, resulting in brainstem inflammation or encephalitis. We report the case of a 66-year-old male patient with a primary manifestation of medulla injury of the glossopharyngeal and vagus nerves, combined with a medulla lesion, who was misdiagnosed with lateral medullary syndrome. Facial nerve injury and earache subsequently occurred and human herpes virus 3 (VZV) was detected by second-generation sequencing of the cerebrospinal fluid. The final diagnosis was varicella zoster encephalitis, which improved after antiviral therapy.


Assuntos
Encefalite por Varicela Zoster/complicações , Traumatismos do Nervo Glossofaríngeo/complicações , Bulbo/patologia , Traumatismos do Nervo Vago/complicações , Idoso , Imagem de Difusão por Ressonância Magnética , Encefalite por Varicela Zoster/diagnóstico por imagem , Traumatismos do Nervo Glossofaríngeo/diagnóstico por imagem , Humanos , Masculino , Bulbo/diagnóstico por imagem , Traumatismos do Nervo Vago/diagnóstico por imagem
9.
BMC Neurol ; 19(1): 28, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30782140

RESUMO

BACKGROUND: Periodic alternating ping-pong gaze (PPG) is a rare disease with few reports. To our knowledge, there was no report on anti GQ1b antibody syndrome accompanied by PPG. This paper reported a case of anti GQ1b antibody syndrome with Bickerstaff's Encephalitis (BBE) overlapping classic Guillain-Barre Syndrome (GBS) after aortic valve replacement, accompanied by an excessive PPG in the course of diagnosis and treatment, this was indeed rarely. CASE PRESENTATION: A 55-year-old male patient was admitted to our hospital with intermittent chest tightness for 3 months, and his condition has worsened in the past 10 days. Aortic valve replacement was performed because of the existence of the moderate and severe stenosis of aortic valve. Horizontal movement of the eyeball was involuntarily slow. The eyeball hovered and returned from one side to the other horizontally for 3-4 s per cycle. In combination with the patient's typical clinical and laboratory tests, the final diagnosis was anti GQ1b antibody syndrome BBE combined with GBS, accompanied by saccadic ping pong gaze. Intravenous immunoglobulin (0.4 g/kg) was given for immunomodulation, methylprednisolone (1000 mg) therapy and symptomatic treatment were performed in the patient. CONCLUSIONS: The patients were discharged from hospital on the thirtieth day because of economic reasons. After 6 months of follow up, the patients left behind a lack of fluency in speech and limb mobility, but the basic life can be taken care of by himself.


Assuntos
Procedimentos Cirúrgicos Cardiovasculares/efeitos adversos , Encefalite/imunologia , Gangliosídeos/imunologia , Síndrome de Guillain-Barré/imunologia , Transtornos da Motilidade Ocular/imunologia , Estenose da Valva Aórtica/cirurgia , Autoanticorpos/imunologia , Encefalite/complicações , Encefalite/tratamento farmacológico , Síndrome de Guillain-Barré/complicações , Síndrome de Guillain-Barré/tratamento farmacológico , Próteses Valvulares Cardíacas , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Pessoa de Meia-Idade
10.
J Endod ; 45(3): 302-309.e1, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30803537

RESUMO

INTRODUCTION: This study examined the identity of the microbiome of deep dentinal caries and its correlation with the inflammation status of caries-induced pulpitis. METHODS: Seventy-five cases were diagnosed based on the American Association of Endodontics's diagnostic criteria and divided into 4 groups: normal pulp with deep caries (NP; n = 13), reversible pulpitis with only cold-evoked pain (CRP; n = 17), reversible pulpitis with both cold/heat-evoked pain (CHRP; n = 24), and symptomatic irreversible pulpitis (SIP; n = 21). Samples were sequenced by 16S rDNA. Alpha and beta diversity were determined. Linear discriminant analysis effect size (LEfSe) analysis was used to detect intergroup differences, and receiver operating characteristic (ROC) curves were generated to assess the role of the caries microbiome in caries-induced pulpitis. RESULTS: The 16S rDNA sequencing yielded 9100 operational taxonomic units. Lactobacillus had the highest relative abundance at the genus level among the 4 groups. There were significant differences in the distribution of the microbiome among the groups. In an alpha diversity analysis, species richness differed between the CRP group and the other groups. In a beta diversity analysis, the distribution of microorganisms in the SIP group was significantly different from those in the other 3 groups. LEfSe analysis indicated substantial differences in the microbiome among the groups, and the areas under the ROC curves (AUC) were all high (AUC: 0.734-0.952). CONCLUSIONS: Characterization of the caries microbiome has the potential to become an auxiliary method for the diagnosis of pulpitis. This finding may prompt new research on diagnostic strategies for caries-induced pulpitis.


Assuntos
Cárie Dentária/diagnóstico , Cárie Dentária/microbiologia , Lactobacillus/isolamento & purificação , Microbiota , Pulpite/diagnóstico , Pulpite/microbiologia , Adolescente , Adulto , Criança , Feminino , Humanos , Lactobacillus/genética , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA/métodos , Adulto Jovem
11.
Transplantation ; 103(3): 502-511, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30211824

RESUMO

BACKGROUND: Advances in immunosuppressive therapy have significantly improved short-term but not long-term survival of cardiac transplant recipients; this is largely due to severe cardiac allograft vasculopathy (CAV). Glucagon-like peptide-1 receptor (GLP-1R)-based therapy exerts physiological effects on the cardiovascular system in addition to its traditional role in controlling glucose. We have investigated the effects of liraglutide, a GLP-1R agonist, on the development of CAV in a murine heart transplant model. METHODS: Heterotopic murine cardiac transplantation was performed with a major histocompatibility complex class II-mismatched model. Recipient mice were subcutaneously administered vehicle (0.9% saline solution) or liraglutide (300 µg·kg every 12 hours) from the day of transplantation. Allografts were harvested at 2 or 8 weeks and histologically analyzed. Inflammatory infiltrates were measured by immunohistochemistry, and immunofluorescence and western blotting analyzes were used to evaluate GLP-1R expression and markers of endothelial-to-mesenchymal transition (EndMT) in cardiac allografts and human coronary artery endothelial cells challenged with transforming growth factor-beta 1. RESULTS: Glucagon-like peptide-1 receptor was predominantly localized to vascular endothelial cells and was upregulated in cardiac allografts after liraglutide treatment. Liraglutide ameliorated CAV and cardiac fibrosis with reduced inflammatory cell infiltration and downregulated expression of adhesion molecules. Liraglutide inhibited EndMT in allografts and attenuated EndMT by inhibiting Smad3 activation in transforming growth factor-beta 1-treated human coronary artery endothelial cells. CONCLUSIONS: Administration of liraglutide from the time of transplantation upregulated GLP-1R in the transplanted heart and reduced cardiac fibrosis, inflammation, and CAV development. Therefore, liraglutide may be a novel therapy for CAV.


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Liraglutida/farmacologia , Doenças Vasculares/tratamento farmacológico , Animais , Vasos Coronários/patologia , Modelos Animais de Doenças , Células Endoteliais/citologia , Fibrose , Glucose/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Imuno-Histoquímica , Imunossupressão , Imunossupressores/uso terapêutico , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Smad3/metabolismo
12.
Medicine (Baltimore) ; 97(25): e11192, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29924039

RESUMO

RATIONALE: Study reported an extremely rare case of trigeminal neuralgia, vestibular paroxysmia, and hemifacial spasm successively occurring in a patient with vertebrobasilar dolichoectasia (VBD). PATIENT CONCERNS: A 66-year-old female patient presented with episodic vertigo for 20 days before she was admitted to our hospital. Vertigo suddenly occurred when the patient rotated her head 20 days ago, the symptoms of vertigo were improved after continuous 1 to 3 seconds, and similar symptoms were repeated in sleep and rest, with a frequency of 30 to 40 times per day. The patient had a history of hypertension with poor blood pressure control for more than 20 years. DIAGNOSES: The final diagnosis was vertebrobasilar dolichectasia, right trigeminal neuralgia, and vestibular paroxysmia. INTERVENTIONS: Vitamin B1 (10 mg), methylcobalamin (0.5 mg), and carbamazepine (0.1 g) were given orally 3 times a day to relieve the symptoms. OUTCOMES: On the seventh day of drug treatment, the symptoms of paroxysmal vertigo and trigeminal neuralgia were completely relieved, but occasional episodes occurred during the follow-up period. Five months after discharge, right hemifacial spasm appeared in the patient, which did not affect the quality of life of the patient, so the patient did not choose further treatment. Six months after discharge, the patient was lost to follow-up. LESSONS: Comprehensive treatment to control VBD risk factors, delay the progression of VBD, and improve clinical symptoms may have a better effect on such patients. However, further research is needed.


Assuntos
Espasmo Hemifacial/complicações , Neuralgia do Trigêmeo/complicações , Insuficiência Vertebrobasilar/complicações , Vertigem/complicações , Idoso , Analgésicos não Entorpecentes/uso terapêutico , Artéria Basilar/anormalidades , Artéria Basilar/patologia , Carbamazepina/administração & dosagem , Carbamazepina/uso terapêutico , Protocolos Clínicos , Feminino , Humanos , Perda de Seguimento , Tiamina/administração & dosagem , Tiamina/uso terapêutico , Neuralgia do Trigêmeo/diagnóstico , Neuralgia do Trigêmeo/tratamento farmacológico , Artéria Vertebral/anormalidades , Artéria Vertebral/patologia , Insuficiência Vertebrobasilar/diagnóstico , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/tratamento farmacológico , Vertigem/diagnóstico , Vertigem/tratamento farmacológico , Vertigem/etiologia , Vitamina B 12/administração & dosagem , Vitamina B 12/análogos & derivados , Vitamina B 12/uso terapêutico , Complexo Vitamínico B/uso terapêutico
13.
Eur Biophys J ; 47(3): 225-236, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28875401

RESUMO

Laccase (benzenediol: oxygen oxidoreductases, EC1.10.3.2) is a multi-copper oxidase capable of oxidizing a variety of phenolic and other aromatic organic compounds. The catalytic power of laccase makes it an attractive candidate for potential applications in many areas of industry including biodegradation of organic pollutants and synthesis of novel drugs. Most laccases are vulnerable to high salt and have limited applications. However, some laccases are not only tolerant to but also activated by certain concentrations of salt and thus have great application potential. The mechanisms of salt-induced activity enhancement of laccases are unclear as yet. In this study, we used dynamic light scattering, size exclusion chromatography, analytical ultracentrifugation, intrinsic fluorescence emission, circular dichroism, ultraviolet-visible light absorption, and an enzymatic assay to investigate the potential correlation between the structure and activity of the marine-derived laccase, Lac15, whose activity is promoted by low concentrations of NaCl. The results showed that low concentrations of NaCl exert little influence on the protein structure, which was partially folded in the absence of the salt; moreover, the partially folded rather than the fully folded state seemed to be favorable for enzyme activity, and this partially folded state was distinctive from the so-called 'molten globule' occasionally observed in active enzymes. More data indicated that salt might promote laccase activity through mechanisms involving perturbation of specific local sites rather than a change in global structure. Potential binding sites for chloride ions and their roles in enzyme activity promotion are proposed.


Assuntos
Cloretos/farmacologia , Haloferax volcanii/enzimologia , Lacase/metabolismo , Cobre/metabolismo , Relação Dose-Resposta a Droga , Concentração de Íons de Hidrogênio , Lacase/química , Ligação Proteica/efeitos dos fármacos , Estrutura Secundária de Proteína/efeitos dos fármacos , Estrutura Terciária de Proteína/efeitos dos fármacos , Especificidade por Substrato
14.
Phys Chem Chem Phys ; 19(36): 25214-25219, 2017 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-28885634

RESUMO

Phosphorous oxide (PxOy)-incorporated carbon nanotubes (PCNTs) and nitric acid treated carbon nanotubes (OCNTs) are first synthesized, then phosphorous modified palladium nanoparticles (Pd-P NPs) supported on PCNTs (Pd-P/PCNTs) and OCNTs (Pd-P/OCNTs) are synthesized and employed as electrocatalysts in a methanol oxidation reaction. Pd-P/PCNTs show enhanced electrocatalytic activity and stability in comparison to Pd-P/OCNTs. Combining surface analysis and electrochemical performance, PxOy incorporated into CNTs could create anchoring sites for Pd ions and P precursors, which could facilitate the synthesis of Pd-P NPs in an aqueous solution containing Pd ions and sodium hypophosphite serving as a reducing agent and a P source. The electronic modification of embedded Pd-P NPs on PxOy-incorporated CNTs accounts for the enhanced electrochemical performance of Pd-P/PCNTs.

15.
J Org Chem ; 82(10): 5263-5273, 2017 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-28421753

RESUMO

Ru(II)-catalyzed redox-neutral [3+2] annulation reactions of N-ethoxycarbamoyl indoles and internal alkynes via C-H bond activation are reported. This method features a broad internal alkyne scope, including various aryl/alkyl-, alkyl/alkyl-, and diaryl-substituted alkynes, good to excellent regioselectivity, diverse functional group tolerance, and mild reaction conditions. The N-ethoxycarbamoyl directing group, temperature, CsOAc, and ruthenium catalyst proved to be crucial for conversion and high regioselectivity. Additionally, preliminary mechanistic experiments were conducted, and a possible mechanism was proposed.

16.
Stroke Vasc Neurol ; 2(4): 184-188, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29507778

RESUMO

Background and purpose: Clinical features of epileptic seizures after cerebral venous sinus thrombosis (CVST) among Chinese patients are not known, and it is still controversial whether seizures would affect the outcome of CVST. Methods: In a Chinese hospital-based study of consecutive patients with CVST between 2003 and 2015, we described the clinical features of seizures and determined the predictors of seizure onset using multivariable logistic regression analysis. We also compared the in-hospital case-fatality and short-term functional outcome (modified Rankin Scale (mRS) at discharge) in patients with versus without seizures using ordinal regression analysis. Results: Among 151 patients with CVST, 52 (34.4%) presented seizures, of which 42 (80.8%) were generalised seizures. Male gender (OR 6.32, 95% CI 2.06 to 19.35, p=0.001), motor deficits (OR 4.89, 95% CI 1.52 to 15.68, p=0.008), intracerebral haemorrhage (OR 3.93, 95% CI 1.16 to 13.26, p=0.027), cerebral infarction (OR 3.78, 95% CI 1.15 to 12.36, p=0.029) and superior sagittal sinus thrombosis (OR 3.38, 95% CI 91.16 to 9.86, p=0.026) were independent predictors for seizures. The overall in-hospital case-fatality rate was 2.0% (3/151), and 21 (13.9%) had mRS >2 at discharge. Compared with patients without seizures, patients with seizures were more likely to have a worse outcome (p=0.02) at discharge, independent of age, gender, clinical presentation, clot burden and presence of parenchymal lesions. Conclusions: In Chinese Han patients, compared with patients without seizures, patients with seizures after CVST had a worse outcome. Risk factors such as male gender, paresis, parenchymal lesion and superior sagittal sinus thrombosis were independently associated with seizure onset after CVST. Generalised seizure was the main form of seizures after CVST, which was obviously different to seizures after strokes of arterial origin.

17.
Biomed Res Int ; 2016: 4896319, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27648446

RESUMO

This research was aimed at discovering the serological and histological changes in cardiac and hepatic tissue after electric shock. The CK-MB, ALT, and AMS indexes were tested with serological methods. Moreover, the Bcl-2, Bax, and Hsp-60 expression levels were carefully measured. An electrical injury model was established by giving rats electric shocks at 110 V with alternating electric current. Blood samples from the rats were analyzed for the biochemical indexes. The degrees of pathological changes in the heart and liver were evaluated using IHC staining for Bcl-2, Bax, and Hsp-60. The levels of CK-MB in the electrical injury group rapidly peaked at 0.5 hours after the electric shock. Additionally, the levels of Bcl-2, Bax, and Hsp-60 in the cardiac and hepatic tissues changed regularly after the electrical injury and exhibited apparent differences from the levels in the control group. CK-MB, ALT, and AMS were altered regularly after electric shock, and these results provide significant information for clinical and medicolegal practice. This research has shed light on the assessment of electrical injury without obvious electrical burns. Furthermore, the findings obtained for Bcl-2/Bax and Hsp-60 can also facilitate pathological diagnosis and the identification of antemortem and postmortem electrical injury.


Assuntos
Biomarcadores/sangue , Eletrochoque , Jurisprudência , Fígado/patologia , Miocárdio/patologia , Animais , Proteínas de Choque Térmico/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Masculino , Miocárdio/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/metabolismo
18.
J Med Chem ; 59(8): 3826-39, 2016 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-27031406

RESUMO

A series of indoline and indole derivatives were designed, synthesized, and evaluated as selective α1A-adrenergic receptor (α1A-AR) antagonists for the treatment of benign prostatic hyperplasia (BPH). In this study, two highly selective and potent α1A-AR antagonists, compounds (R)-14r (IC50 = 2.7 nM, α1B/α1A = 640.1, α1D/α1A = 408.2) and (R)-23l (IC50 = 1.9 nM, α1B/α1A = 1506, α1D/α1A = 249.6), which exhibited similar activities and better selectivities in cell-based calcium assays as compared with the marketed drug silodosin (IC50 = 1.9 nM, α1B/α1A = 285.9, α1D/α1A = 14.4), were identified. In the functional assays with isolated rat tissues, compounds (R)-14r and (R)-23l also showed high potency and uroselectivity. Most importantly, (R)-14r and (R)-23l can significantly decrease the micturition frequency and increase the mean voided volume of the BPH rats in a dose-dependent manner, making them worthy of further investigation for the development of anti-BPH agents.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/química , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Indóis/síntese química , Indóis/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 1/síntese química , Antagonistas de Receptores Adrenérgicos alfa 1/farmacocinética , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Animais , Área Sob a Curva , Desenho de Drogas , Meia-Vida , Humanos , Indóis/química , Indóis/farmacocinética , Masculino , Hiperplasia Prostática/tratamento farmacológico , Ratos , Relação Estrutura-Atividade
19.
Biomed Res Int ; 2016: 5985327, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26949703

RESUMO

The role of brain natriuretic peptide (BNP) in the prevention of contrast-induced nephropathy (CIN) is unknown. This study aimed to investigate BNP's effect on CIN in chronic kidney disease (CKD) patients undergoing elective percutaneous coronary intervention (PCI) or coronary angiography (CAG). The patients were randomized to BNP (0.005 µg/kg/min before contrast media (CM) exposure and saline hydration, n = 106) or saline hydration alone (n = 103). Cystatin C, serum creatinine (SCr) levels, and estimated glomerular filtration rates (eGFR) were assessed at several time points. The primary endpoint was CIN incidence; secondary endpoint included changes in cystatin C, SCr, and eGFR. CIN incidence was significantly lower in the BNP group compared to controls (6.6% versus 16.5%, P = 0.025). In addition, a more significant deterioration of eGFR, cystatin C, and SCr from 48 h to 1 week (P < 0.05) was observed in controls compared to the BNP group. Although eGFR gradually deteriorated in both groups, a faster recovery was achieved in the BNP group. Multivariate logistic regression revealed that using >100 mL of CM (odds ratio: 4.36, P = 0.004) and BNP administration (odds ratio: 0.21, P = 0.006) were independently associated with CIN. Combined with hydration, exogenous BNP administration before CM effectively decreases CIN incidence in CKD patients.


Assuntos
Meios de Contraste/efeitos adversos , Glomerulonefrite/tratamento farmacológico , Peptídeo Natriurético Encefálico/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Insuficiência Renal Crônica/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária/efeitos adversos , Creatinina/metabolismo , Feminino , Glomerulonefrite/induzido quimicamente , Glomerulonefrite/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/metabolismo , Intervenção Coronária Percutânea/efeitos adversos , Proteínas Recombinantes/metabolismo , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/diagnóstico por imagem , Fatores de Risco
20.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 32(2): 146-151, 2016 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-29931867

RESUMO

OBJECTIVE: In order to provide the experimental basis for the prevention of exercise-induced cardiac injury, we evaluated the effects of nuclear factor erythroid-2-related factor2(Nrf2) on the changes of cardiac function and electrocardiogram in rats after exhaustive exercise. METHODS: SD rats were randomly divided into 5 groups (n=6):control group (Con), exhaustied exercise group (EE), 6h, 12 h, 24 h recovery from exhaustied exercise group(EER6 EER12 EER24). The animal models of exercise-induced myocardial injury were established according to Thomas' method.Rats were forced to swim until they were exhausted.The electrocardiograms were recorded in conscious rats. Cardiac function of rats was recorded and analyzed by Millar pressure-volume system. The changes of catalase(CAT), glutathione peroxidase(GPX), Nrf2 and reactive oxygen speies(ROS) were detected by ELISA, respectively. RESULTS: ①Compared with the control group and recovery groups(EER6, EER12, and EER24), the heart rate (HR), left ventricular end systolic pressure (Pes), arterial elasticity (Ea), the maximum rate of left ventricular pressure rise (dP/dtmax), peak rate of left ventricular pressure decline (-dP/dtmin) and left ventricular end diastolic pressure volume relationship curve slope (ESPVR) in the EE group decreased significantly, while left ventricular end diastolic volume (Ved), Pes, left ventricular end systolic volume (Ves), stroke volume, and Tau value increased significantly. Besides, HR, Pes, dP/dtmax, -dP/dtmin in recovery groups were significantly different with those in EE group, but there had no difference with those in the Con group. ②Compared with the control group, heart rate was increased, QT intervals were prolonged P wave, R wave and ST segments were increased in EE and recovery groups, but the changes of above-mentioned indexes in recovery groups had no statistical significant difference with those in EE group.③ Compared with the control group,the contents of ROS, Nrf2 were increased in EE group, while the content of GPX was decreased. Moreover, the content of CAT in EER6 group was the lowest in all groups. ④ The level of Nrf2 in serum was positively correlated with ROS and -dP/dtmin, and negatively correlated with HR, Ea. The level of ROS in Serum was positively correlated with EF, -dP/dtmin, and was negatively correlated with HR, Ea, dP/dtmax. CONCLUSIONS: Exhausted exercise caused changes of cardiac bioelectricity, impaired both the cardiac systolic and diastolic function, especially the diastolic disfunction. However, with recovery time after exhausted exercise prolonged, cardiac systolic and diastolic function recovered gradually, which was related to the reduced oxidative stress levels modulated by the increased Nrf2-induced changes of GPX and CAT.


Assuntos
Cardiomiopatias/fisiopatologia , Fator 2 Relacionado a NF-E2/sangue , Condicionamento Físico Animal/efeitos adversos , Animais , Pressão Sanguínea , Catalase/metabolismo , Eletrocardiografia , Glutationa Peroxidase/metabolismo , Frequência Cardíaca , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/sangue , Volume Sistólico , Função Ventricular Esquerda
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