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1.
Bioorg Chem ; 94: 103413, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31791679

RESUMO

A series of new ferulic acid derivatives were designed, synthesized and evaluated as multi-target inhibitors against Alzheimer's disease. In vitro studies indicated that most compounds showed significant potency to inhibit self-induced ß-amyloid (Aß) aggregation and acetylcholinesterase (AChE), and had good antioxidant activity. Specifically, compound 4g exhibited the potent ability to inhibit cholinesterase (ChE) (IC50, 19.7 nM for hAChE and 0.66 µM for hBuChE) and the good Aß aggregation inhibition (49.2% at 20 µM), and it was also a good antioxidant (1.26 trolox equivalents). Kinetic and molecular modeling studies showed that compound 4g was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Moreover, compound 4g could remarkably increase PC12 cells viability in hydrogen peroxide-induced oxidative cell damage and Aß-induced cell damage. Finally, compound 4g had good ability to cross the BBB using the PAMPA-BBB assay. These results suggested that compound 4g was a promising multifunctional ChE inhibitor for the further investigation.

2.
Neural Regen Res ; 14(4): 642-648, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30632504

RESUMO

Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy. However, the specific brain networks implicated in neonatal cases remain poorly understood. In this study, we recruited 14 term-born infants with mild hypoxic ischemic encephalopathy and 14 term-born infants with severe hypoxic ischemic encephalopathy from Changzhou Children's Hospital, China. Resting-state functional magnetic resonance imaging data showed efficient small-world organization in whole-brain networks in both the mild and severe hypoxic ischemic encephalopathy groups. However, compared with the mild hypoxic ischemic encephalopathy group, the severe hypoxic ischemic encephalopathy group exhibited decreased local efficiency and a low clustering coefficient. The distribution of hub regions in the functional networks had fewer nodes in the severe hypoxic ischemic encephalopathy group compared with the mild hypoxic ischemic encephalopathy group. Moreover, nodal efficiency was reduced in the left rolandic operculum, left supramarginal gyrus, bilateral superior temporal gyrus, and right middle temporal gyrus. These results suggest that the topological structure of the resting state functional network in children with severe hypoxic ischemic encephalopathy is clearly distinct from that in children with mild hypoxic ischemic encephalopathy, and may be associated with impaired language, motion, and cognition. These data indicate that it may be possible to make early predictions regarding brain development in children with severe hypoxic ischemic encephalopathy, enabling early interventions targeting brain function. This study was approved by the Regional Ethics Review Boards of the Changzhou Children's Hospital (approval No. 2013-001) on January 31, 2013. Informed consent was obtained from the family members of the children. The trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800016409) and the protocol version is 1.0.

3.
Biochem Biophys Res Commun ; 501(2): 478-485, 2018 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-29746863

RESUMO

The epigenetic effects on expression of non-coding RNAs (e.g. microRNAs) of environmental toxin bisphenol A (BPA) have extended our understanding of the etiology of human reproductive disorders including hypospermatogenesis and androgen deficiency. BPA-induced miR-146a-5p is a potent regulator of endocrine and immune homeostasis, but its role in testis remain unexplored. We show here that in murine testis, miR-146a-5p was exclusively expressed in interstitial Leydig cells (LCs). This expression was significantly induced by BPA exposure. Consequently, the elevated miR-146a-5p exacerbated the deleterious effects of BPA on testicular steroidogenesis. Mechanistically, miR-146a-5p repressed the expression of Mta3, a pivotal chromatin remodeling transcription factor recently involved in controlling the steroidogenic activity, via directly targeting its 3'UTR. This repression thereafter rendered LCs more sensitive to BPA-elicited inhibitory effects. Conversely, ectopic expression of hMTA3 successfully rescued miR-146a-5p-elicited inhibitory effects on testicular steroidogenesis in BPA-challenged LCs. Taken together, the available data provide novel evidence that deregulation of testicular miR-146a-5p/Mta3 cascade mediates, at least in part, the steroidogenic dysfunction caused by BPA exposure.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Proteínas de Neoplasias/genética , Fenóis/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Esteroides/metabolismo , Testículo/efeitos dos fármacos , Regiões 3' não Traduzidas/efeitos dos fármacos , Animais , Epigênese Genética/efeitos dos fármacos , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Neoplasias/metabolismo , Testículo/metabolismo
4.
Biochem Biophys Res Commun ; 490(3): 786-793, 2017 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-28645613

RESUMO

Although both insulin and estrogen receptor α (ERα) are known to exert inhibitory effects on testicular steroidogenesis, it remains unknown whether these pathways regulate testosterone (T) production under certain pathological conditions [e.g., type 2 diabetes mellitus (T2DM)] in a coordinated manner. Here, we found that the expression of forkhead box protein A3 (Foxa3), an essential transcriptional regulator engaged in adipogenesis and energy metabolism, was significantly down-regulated in the Leydig cells (LCs) from T-deficient T2DM mice. Functionally, upon hCG stimulation, Foxa3 recruits to the Esr1 promoter and suppresses the transactivation of Esr1 gene. Disruption of this recruitment by T2DM-elicited hyperinsulinemia led to abnormal activation of ERα pathway, inhibited steroidogenic enzyme genes expression, and thus caused inadequate T production. Therapeutically, insulin-impaired and Foxa3 ablation-compromised steroidogenesis were effectively rescued by a pharmacological inhibitor of the ERα pathway. These findings reveal an obligatory coregulatory role of Foxa3 in the regulation of ERα expression and of the Foxa3/ERα cascade, at least in part, in the pathogenesis of androgen deficiency caused by T2DM.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Receptor alfa de Estrogênio/metabolismo , Fator 3-gama Nuclear de Hepatócito/metabolismo , Células Intersticiais do Testículo/metabolismo , Transdução de Sinais , Testosterona/metabolismo , Animais , Células Cultivadas , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Regulação para Baixo , Receptor alfa de Estrogênio/genética , Fator 3-gama Nuclear de Hepatócito/genética , Células Intersticiais do Testículo/patologia , Masculino , Camundongos Endogâmicos BALB C , Esteroides/metabolismo , Ativação Transcricional
5.
Neural Regen Res ; 12(4): 603-609, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28553341

RESUMO

With improvements in care of at-risk neonates, more and more children survive. This makes it increasingly important to assess, soon after birth, the prognosis of children with hypoxic-ischemic encephalopathy. Computed tomography, ultrasound, and conventional magnetic resonance imaging are helpful to diagnose brain injury, but cannot quantify white matter damage. In this study, ten full-term infants without brain injury and twenty-two full-term neonates with hypoxic-ischemic encephalopathy (14 moderate cases and 8 severe cases) underwent diffusion tensor imaging to assess its feasibility in evaluating white matter damage in this condition. Results demonstrated that fractional anisotropy, voxel volume, and number of fiber bundles were different in some brain areas between infants with brain injury and those without brain injury. The correlation between fractional anisotropy values and neonatal behavioral neurological assessment scores was closest in the posterior limbs of the internal capsule. We conclude that diffusion tensor imaging can quantify white matter injury in neonates with hypoxic-ischemic encephalopathy.

7.
Fa Yi Xue Za Zhi ; 26(2): 116-9, 2010 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-20653138

RESUMO

OBJECTIVE: In order to improve accuracy of forensic expert conclusion and provide scientific and reasonable accordance for revising identifying criteria for the injury degree, correlation between clinical classification and injury certification of acute closed head trauma were explored. METHODS: A total of 30 cases about acute closed head trauma were selected. Comparison and analysis were made about their differences and the correlation between the clinical classification and the injury degree certification. RESULTS: Mild craniocerebral injury is equal to mild or moderate injury, moderate craniocerebral injury is equivalent to mild or severe injury, severe craniocerebral injury is mostly equivalent to severe injury. CONCLUSION: There are some correlation between the clinical classification and the injury certification in acute closed head trauma. It is necessary to refer to the criteria of clinical classification when revising identifying criteria for the injury degree so as to enhance scientific rigor and rationality.


Assuntos
Prova Pericial/normas , Traumatismos Cranianos Fechados/diagnóstico , Escala de Gravidade do Ferimento , Adulto , Concussão Encefálica/etiologia , Concussão Encefálica/patologia , Feminino , Patologia Legal/normas , Traumatismos Cranianos Fechados/classificação , Traumatismos Cranianos Fechados/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Hemorragia Subaracnóidea/etiologia , Hemorragia Subaracnóidea/patologia , Adulto Jovem
8.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 4): o867, 2010 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-21580689

RESUMO

In the title compound, C(11)H(15)N(5)O(2), the 1,3,5-triazine ring exhibits a half-chair conformation. An intra-molecular N-H⋯O inter-action occurs. In the crystal structure, mol-ecules are connected by inter-molecular C-H⋯O and N-H⋯N hydrogen bonds, forming a zigzag chain along the b axis.

9.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 7): o1827, 2010 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-21588033

RESUMO

In the title compound, C(14)H(11)Cl(2)N(3)S, the thia-zole ring is in an envelope conformation with the -CH(2)- group bonded to the S atom forming the flap. The crystal structure is stabilized by weak inter-molecular C-H⋯Cl and C-H⋯N hydrogen bonds.

10.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 8): o2171, 2010 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-21588452

RESUMO

The title compound, C(12)H(12)ClN(3)S, features a thia-zolyl ring having an envelope conformation with the -CH(2)- group bonded to the S atom forming the flap. The C=N double bond has a Z configuration. The crystal structure shows inter-molecular C-H⋯S hydrogen bonds.

11.
Ann Thorac Surg ; 84(1): 156-60, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17588403

RESUMO

BACKGROUND: Sinus of Valsalva aneurysm is a rare cardiac anomaly, and the difference between Asian and Western countries in its occurrence is not well established. This study was designed to investigate the difference between Asian and Western patients. METHODS: Between September 1988 and February 2006, 83 patients with sinus of Valsalva aneurysm underwent surgical repair in our institute. The aneurysms originated from the right and noncoronary sinus in 74 and 9, respectively, and ruptured into the right ventricle in 52 patients, the right atrium in 30, and the left ventricle in 1. Ventricular septal defect (n = 38), aortic regurgitation (n = 21), and bicuspid aortic valve (n = 4) were the common coexisting anomalies. To compare the differences between Asian and Western patients in sinus of Valsalva aneurysm, 1049 cases (654 Asian patients versus 395 Western) were collected from the literature. RESULTS: Sixty-six patients were followed up for 9.6 +/- 3.8 years. The cardiac function of 15 patients with aortic regurgitation was worse than that of those with no aortic regurgitation (p < 0.05). There was no difference between the direct closure and the patch closure (p > 0.05). Analysis of all collected cases revealed that aneurysm of the sinus of Valsalva in Asian patients compared with Western series is characterized by a higher incidence, more aneurysms originating from the right coronary sinus (85.8% versus 67.9%), more aneurysm rupture into the right ventricle (72.5% versus 60%), a higher incidence of association with ventricular septal defect (52.4% versus 37.5%), and lower incidence of association with bicuspid aortic valve (0.6% versus 7.8%). However, both Asian and Western patient series have similar incidence of combination with aortic regurgitation (33.6% versus 32.7%). CONCLUSIONS: Long-term results of ruptured sinus of Valsalva aneurysm are associated with preoperative aortic regurgitation. The difference between Asian and Western patients with ruptured aneurysm of the sinus of Valsalva is significant.


Assuntos
Aneurisma Aórtico/cirurgia , Seio Aórtico/cirurgia , Adolescente , Adulto , Idoso , Aneurisma Aórtico/etnologia , Aneurisma Aórtico/mortalidade , Ruptura Aórtica/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Grupo com Ancestrais do Continente Asiático , Criança , Pré-Escolar , Feminino , Seguimentos , Comunicação Interventricular/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade
12.
Zhonghua Wai Ke Za Zhi ; 44(10): 655-7, 2006 May 15.
Artigo em Chinês | MEDLINE | ID: mdl-16784670

RESUMO

OBJECTIVE: To explore the effects of coronary abnormalities on reconstruction of right ventricular outflow tract in patients with complex congenital heart disease. METHODS: Eighty patients, including tetralogy of Fallot 14 cases and double outlet right ventricle (DORV) 4 cases with anomalous coronary artery, underwent surgical treatment from April 1989 to May 2004. The coronary diseases included single left or right coronary artery in 11 cases, left anterior descending coronary artery originating from right coronary artery in 6 cases, vascular plexus on right outflow tract in 1 case. One-stage correction was undergone in 17 cases, palliative procedure in 1 case. The reconstruction methods were as follows: mobilizing coronary artery and expanding incision under coronary artery with pericardial patches in 4 cases; repairing ventricular septal defect (VSD) via the incision beneath the coronary artery and expanding right ventricular outlet tract (RVOT) and pulmonary via longitudinal incision over the coronary artery in 3 cases. VSD were repaired via right atrium and minimal incision on RVOT plus incision on pulmonary were made to expand RVOT. Trunk of pulmonary were anastomosis with RVOT in 3 cases. Homograft valved aorta were used in 3 cases. RESULTS: One case died of serious low cardiac output syndrome postoperatively. There was no critical complication of hemorrhage and respiratory tract. Oxygen saturation rose from 68.0% to 82.0% after treated by palliative procedure. Seventeen cases were followed from 10 months to 8 years, 1 case suddenly died with no clear cause. Three cases were with residual leak, 3 with residual obstruction. CONCLUSIONS: Surgical procedure should be selected according to the characteristics of coronary disease with complex congenital heart disease.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Anomalias dos Vasos Coronários/cirurgia , Dupla Via de Saída do Ventrículo Direito/cirurgia , Tetralogia de Fallot/cirurgia , Adolescente , Criança , Pré-Escolar , Anomalias dos Vasos Coronários/complicações , Dupla Via de Saída do Ventrículo Direito/complicações , Feminino , Seguimentos , Humanos , Lactente , Masculino , Tetralogia de Fallot/complicações , Resultado do Tratamento
13.
Zhonghua Yi Xue Za Zhi ; 85(41): 2910-5, 2005 Nov 02.
Artigo em Chinês | MEDLINE | ID: mdl-16324364

RESUMO

OBJECTIVE: To construct a recombinant vector that expresses 5 shRNAs targeting on the rat ventricular myocyte Kir2.1 gene in tandem and its effect in vitro METHODS: Ventricular myocytes were collected from newborn Wistar rats and cultured. Five sites targeting on the rat Kir2.1 gene were selected. Accordingly 5 pairs of oligonucleotide fragments were designed, synthesized, and annealed to obtain double-stranded DNAs. The 5 pairs of oligonucleotide were then cloned into the vector pGenesil-1 by repeated excision and ligation successively. The tandem recombinant vector pEGFP6-1Kir2.1 was thus constructed and transfected into the cultured rat myocytes. RT-PCR and Western blotting were used to detect the mRNA and protein expression of Kir2.1 in the myocytes. Sequence not related to Kir2.1 sequence with mismatched bases was designed and used as control. RESULTS: A recombinant vector that expresses 5 shRNAs targeting on the rat ventricular myocyte Kir2.1 gene in tandem was constructed. 96 hours after the transfection RT-PCR showed that the Kir2.1 mRNA transcription was suppressed by 83, 6%, and Western blotting showed that the Kir2.1 protein transcription was suppressed by 68.1% in comparison with the control. CONCLUSION: The vector that expresses the 5 shRNAs targeting on the rat ventricular myocyte Kir2.1 gene in tandem is able to suppress the expression of Kir2.1 in rat ventricular myocytes. Application of such vector may be a new method to produce a new type of heart biological pacemaker.


Assuntos
Inativação Gênica , Vetores Genéticos , Miócitos Cardíacos/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/genética , RNA Interferente Pequeno/genética , Animais , Animais Recém-Nascidos , Células Cultivadas , Miócitos Cardíacos/citologia , Canais de Potássio Corretores do Fluxo de Internalização/biossíntese , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Wistar , Sequências de Repetição em Tandem , Transfecção
14.
Zhonghua Wai Ke Za Zhi ; 42(13): 808-11, 2004 Jul 07.
Artigo em Chinês | MEDLINE | ID: mdl-15363302

RESUMO

OBJECTIVE: To review retrospectively the experience of surgical repair of sinus of valsalva aneurysm (SVA) in 70 patients. METHODS: Between September, 1988 and October, 2003, Seventy patients with SVA underwent surgical repair by the aid of general anesthesia and cardiopulmonary bypass, comprised 1.4% (70/4960) of all open-heart operation. Forty-five were male and 25 female. Age ranged from 3 to 69 years old [mean (29 +/- 15) years]. The aneurysms ruptured into the right ventricle in 46 patients, right atrium in 23 and left ventricle in 1 respectively. The aneurysms originated from right and noncoronary sinus in 61 patients (87%) and 9 patients (13%) respectively. The most common associated cardiovascular lesions were ventricular septal defect (VSD, n = 34) and aortic valve incompetence (n = 21). Repairs were achieved through an incision in right atriotomy, right ventriculotomy or aortotomy only or both aortotomy and right atriotomy (or right ventriculotomy). The defects in the sinus of valsalva was repaired with either direct sutures (n = 43) or a patch (n = 27). The aortic valve was replaced in 6 patients. RESULTS: There were no deaths in early time after repair. Postoperative hospital stay was 8 approximately 33 days [mean +/- standard deviation, (14.3 +/- 6.4) days] before 1997 and 6 approximately 15 days [mean +/- standard deviation, (9.1 +/- 2.6) days] after 1997 respectively. Complications included infection (n = 4), hemorrhage (n = 4), pneumothorax (n = 1), arrhythmia (n = 4) and residual shunt (n = 1) of VSD. Fifty-three (76%) patients (2 months approximately 13 years) were followed-up [mean +/- standard deviation, (6.6 +/- 3.8) years]. All patients survived except that one died of rupture of dissecting aortic aneurysm 7 years after operation. CONCLUSIONS: The ruptured sinus of valsalva aneurysm and unruptured sinus of valsalva aneurysm with ventricle septal defect or(and) aortic valve regurgitation should be repaired surgically as soon as the diagnosis was confirmed. Long-term results are associated with preoperative aortic valve regurgitation.


Assuntos
Aneurisma Aórtico/cirurgia , Ruptura Aórtica/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Comunicação Interventricular/cirurgia , Seio Aórtico , Adolescente , Adulto , Idoso , Aneurisma Aórtico/complicações , Insuficiência da Valva Aórtica/complicações , Criança , Pré-Escolar , Feminino , Comunicação Interventricular/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Seio Aórtico/cirurgia , Resultado do Tratamento
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