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1.
Signal Transduct Target Ther ; 6(1): 329, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471087

RESUMO

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

2.
Eur J Pain ; 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34288242

RESUMO

BACKGROUND: The mechanism for reduced pain sensitivity associated with Alzheimer's disease (AD) has not been illustrated. We hypothesize that amyloid beta 1-42 (Aß1-42) in the spinal cord acts as an endogenous analgesic peptide to suppress pain induced by nerve injury. METHODS: We used chronic constriction injury of the sciatic nerve (CCI) to produce neuropathic pain in Sprague-Dawley rats. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to determine the level of Aß1-42, the expression of Wnt3a/5b and glial activation in the spinal cord. Western blotting was used to determine the expression of interleukins, the phosphorylation of NR2B and ERK1/2, and the nuclear accumulation of transcriptional factors YAP/TAZ. Thermal hyperalgesia and mechanical allodynia were assessed after CCI and pharmacological manipulations through intrathecal administration. RESULTS: Nerve injury increases spinal level of Aß1-42, while intrathecal administration of MK-8931 reduces the level of Aß1-42 and facilitates mechanical allodynia. Intrathecal administration of Aß1-42 suppresses pain behaviors in the early and late phases of neuropathy. Spinal administration of Aß1-42 regulates the expression of interleukins, reducing glial activation and phosphorylation of NR2B and ERK1/2 in the spinal cord of CCI rats. Furthermore, intrathecal administration of Aß1-42 decreases Wnt5b expression and suppresses the nuclear accumulation of YAP and TAZ. Blocking the interaction between Aß1-42 and Frizzled receptors by cSP5 reverses the analgesic effects of Aß1-42. CONCLUSIONS: These findings suggest that spinal Aß1-42 acts as an endogenous analgesic peptide through regulating cytokines and Wnt pathways. This study may provide a potential target for the development of novel analgesic peptides. SIGNIFICANCE: This study provides an explanation of reduced pain sensitivity associated with Alzheimer's disease. Furthermore, our findings propose a possible physiological function of beta-amyloid1-42 to regulate pain. This study may provide a potential target for the development of novel analgesics based on an existing endogenous peptide.

3.
Cardiovasc Toxicol ; 20(5): 482-491, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32236896

RESUMO

Myocardial fibrosis (MFs) is a crucial pathological process that results in cardiac failure in the development of multiple cardiovascular diseases. Puerarin could reportedly be used to treat a variety of cardiovascular diseases. However, the exact mechanism of puerarin on MFs was not clear enough. The separated primary cardiac fibroblasts (CFs) were induced by lipopolysaccharide (LPS) and treated with puerarin. The levels of TNF-α, IL-6, HMGB1, PARP-1, α-SMA, collagen-1, collagen-3, NF-κB pathways were examined by ELISA, immunofluorescence, RT-qPCR, western blot and immunohistochemistry assays. In addition, MFs rats' model was established using transverse aortic constriction (TAC), and the degree of fibrosis was certified by masson staining. We successfully separated primary CFs, and certified that LPS induction could upregulate the levels of PARP-1, HMGB1, inflammatory cytokines and fibrosis-related proteins (α-SMA, collagen-1 and collagen-3). In addition, we proved that puerarin could weaken MFs, and PARP-1 and HMGB1 expressions, which were induced by LPS in primary CFs. In terms of mechanism, HMGB1 expression could be promoted by PARP-1, and PARP-1 could attenuate the therapeutic effect of puerarin on LPS-induced MFs. Besides, PARP-1-HMGB1-NF-κB pathway was related to the protective effect of puerarin on MFs. In vivo, we also verified the protective efficacy of puerarin on MFs induced by TAC, and puerarin also regulated HMGB1-mediated TLR4-NF-κB signaling pathway. We demonstrated that puerarin could ameliorate MFs by downregulating PARP-1 to inhibit HMGB1-mediated TLR4-NF-κB signaling pathway in LPS-induced primary CFs and TAC-induced MFs rats' model.


Assuntos
Anti-Inflamatórios/farmacologia , Cardiomiopatias/prevenção & controle , Fibroblastos/efeitos dos fármacos , Proteína HMGB1/metabolismo , Isoflavonas/farmacologia , Miocárdio/enzimologia , NF-kappa B/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Cardiomiopatias/enzimologia , Cardiomiopatias/patologia , Células Cultivadas , Modelos Animais de Doenças , Fibroblastos/enzimologia , Fibroblastos/patologia , Fibrose , Lipopolissacarídeos/toxicidade , Miocárdio/patologia , Poli(ADP-Ribose) Polimerase-1/genética , Ratos Wistar , Transdução de Sinais
4.
Biomed Res Int ; 2020: 6406395, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33415151

RESUMO

Adipose-derived stem cells (ADSCs) have been documented as possible candidates for skin rejuvenation. However, the effects of ADSC-derived exosomes on photoaged skin remain to be fully elucidated. This study was aimed at determining the antiaging effects of ADSC-derived exosomes on photoaged skin. Human ADSCs were isolated from the adipose tissue of healthy women and cultured in vitro. Then, exosomes were extracted from the cultured ADSCs, purified by ultracentrifugation, and verified by examination of cell morphology using transmission electron microscopy and the identification of specific biomarkers. Meanwhile, the optimal exosome concentration and treatment time were selected. The photoaged skin model was created by subjecting Sprague-Dawley rats to ultraviolet B radiation. Exosomes were injected into the photoaged skin in a single therapeutic dose. The thickness of the epidermis and dermis was observed by HE staining. The relative mRNA expression of type I collagen, type III collagen, and matrix metalloproteinases (MMP-1 and MMP-3) was determined by real-time PCR. In the rat model of photoaged skin, the injected exosomes markedly decreased the epidermal thickness and increased the dermal thickness of the photoaged skin 7 days after treatment. Moreover, the proportion of the stratum corneum of the epidermis was decreased. Furthermore, real-time RT-PCR showed that the mRNA expression of type I collagen was increased and that of type III collagen, MMP-1, and MMP-3 was decreased. Our results demonstrate that ADSC-derived exosome treatment could significantly improve skin photodamage and that ADSC-derived exosomes may be a potential agent for photoaged skin treatment.


Assuntos
Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Envelhecimento da Pele/efeitos da radiação , Adulto , Animais , Núcleo Celular/metabolismo , Proliferação de Células , Forma Celular , Células Cultivadas , Colágeno/genética , Colágeno/metabolismo , Derme/metabolismo , Exossomos/ultraestrutura , Feminino , Fibroblastos/metabolismo , Humanos , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley
5.
Neurobiol Pain ; 6: 100028, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223142

RESUMO

The cyclic nucleotide signaling, including cAMP-PKA and cGMP-PKG pathways, has been well known to play critical roles in regulating cellular growth, metabolism and many other intracellular processes. In recent years, more and more studies have uncovered the roles of cAMP and cGMP in the nervous system. The cAMP and cGMP signaling mediates chronic pain induced by different forms of injury and stress. Here we summarize the roles of cAMP-PKA and cGMP-PKG signaling pathways in the pathogenesis of chronic pain after nerve injury. In addition, acute dissociation and chronic compression of the dorsal root ganglion (DRG) neurons, respectively, leads to neural hyperexcitability possibly through PAR2 activation-dependent activation of cAMP-PKA pathway. Clinically, radiotherapy can effectively alleviate bone cancer pain at least partly through inhibiting the cancer cell-induced activation of cAMP-PKA pathway. Roles of cyclic nucleotide signaling in neuropathic and inflammatory pain are also seen in many other animal models and are involved in many pro-nociceptive mechanisms including the activation of hyperpolarization-activated cyclic nucleotide (HCN)-modulated ion channels and the exchange proteins directly activated by cAMP (EPAC). Further understanding the roles of cAMP and cGMP signaling in the pathogenesis of chronic pain is theoretically significant and clinically valuable for treatment of chronic pain.

6.
Molecules ; 24(8)2019 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-31013583

RESUMO

In this work, antibacterial activity of finger citron essential oil (FCEO, Citrus medica L. var. sarcodactylis) and its mechanism against food-borne bacteria were evaluated. A total of 28 components in the oil were identified by gas chromatography-mass spectrometry, in which limonene (45.36%), γ-terpinene (21.23%), and dodecanoic acid (7.52%) were three main components. For in vitro antibacterial tests, FCEO exhibited moderately antibacterial activity against common food-borne bacteria: Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Micrococcus luteus. It showed a better bactericidal effect on Gram-positive bacteria than Gram-negative. Mechanisms of the antibacterial action were investigated by observing changes of bacteria morphology according to scanning electron microscopy, time-kill analysis, and permeability of cell and membrane integrity. Morphology of tested bacteria was changed and damaged more seriously with increased concentration and exposure time of FCEO. FCEO showed a significant reduction effect on the growth rate of surviving bacteria and lead to lysis of the cell wall, intracellular ingredient leakage, and consequently, cell death.


Assuntos
Antibacterianos , Citrus/química , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/crescimento & desenvolvimento , Óleos Voláteis , Óleos Vegetais , Antibacterianos/química , Antibacterianos/farmacologia , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Óleos Vegetais/química , Óleos Vegetais/farmacologia
7.
Exp Dermatol ; 28(1): 59-65, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30412649

RESUMO

BACKGROUND: Recent evidence suggests that angiotensin II (Ang II) plays a role in cutaneous wound healing. Mesenchymal stem cells (MSCs) are known as a rich source of cells that re-establish healed skin. However, the potential impact of Ang II on MSC differentiation into keratinocytes is still unknown. OBJECTIVE: The present study was conducted to explore the effect of Ang II on the differentiation of bone marrow-derived MSCs (BM-MSCs) into keratinocytes. METHODS: Bone marrow-derived MSCs were isolated from rat bone marrow and cultured. The expression of Ang II type 1 (AT1 ) and type 2 (AT2 ) receptors was examined by immunofluorescence staining. The differentiation of BM-MSCs into keratinocytes was investigated by flow cytometry or/and histological observation. RESULTS: The BM-MSCs constitutively expressed both AT1 and AT2 receptors. The differentiation of BM-MSCs into keratinocytes was successfully induced. Interestingly, incubation of BM-MSCs with Ang II further promoted the differentiation of BM-MSCs into keratinocyte, which was abolished by pretreament with losartan, an AT1 receptor antagonist, but not by PD123319, an AT2 receptor antagonist. Moreover, the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, the c-Jun N-terminal kinase (JNK) inhibitor SP600125 and the Janus-activated kinase (JAK)2 inhibitor AG490 suppressed Ang II-induced differentiation of BM-MSCs into keratinocytes. The phosphoinositide-3 kinase (PI3K) inhibitor wortmannin and MEK1/2 inhibitor U0126 had no effect on BM-MSC differentiation into keratinocytes. CONCLUSIONS: Our data demonstrated for the first time that Ang II plays a promotive role in the differentiation of BM-MSC into keratinocytes through the AT1 receptor, and that the p38 MAPK, JNK and JAK2 signalling pathways are involved in this process.


Assuntos
Angiotensina II/farmacologia , Diferenciação Celular/efeitos dos fármacos , Linhagem da Célula , Queratinócitos/fisiologia , Sistema de Sinalização das MAP Quinases , Células-Tronco Mesenquimais/fisiologia , Angiotensina II/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 2 de Angiotensina II/farmacologia , Animais , Antracenos/farmacologia , Células da Medula Óssea , Movimento Celular/efeitos dos fármacos , Imidazóis/farmacologia , Janus Quinase 2/metabolismo , Janus Quinases/metabolismo , Queratinócitos/metabolismo , Losartan/farmacologia , Masculino , Células-Tronco Mesenquimais/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Tirfostinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
8.
J Neurosci ; 36(39): 10128-40, 2016 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-27683908

RESUMO

UNLABELLED: Neuropathic pain, often caused by nerve injury, is a major clinical challenge. Mechanisms that underlie neuropathic pain remain elusive and effective medications are limited. Numerous investigations of pain mechanisms have focused on alterations and phenotypic switches of the nociceptive transmitters and modulators, as well as on their receptors and downstream signaling pathways that have already exerted roles in the pain processes of mature nervous systems. We have demonstrated recently that nerve injury may elicit neuronal alterations that recapitulate events occurring during development. Signaling of the representative activated molecule Wnt thus becomes a trigger for the development of neuropathic pain and is a potential therapeutic target. We report that the transcriptional regulators YAP and TAZ, which orchestrate Wnt response via incorporation in the ß-catenin destruction complex, are key in the pathogenesis of neuropathic pain and may serve as an "ON-OFF" switch for neuropathic pain status in rats. Peripheral nerve injury causes rapid-onset and long-lasting nuclear accumulation of YAP/TAZ/ß-catenin in the spinal dorsal horn. Spinal inhibition or knock-down of either YAP or TAZ suppresses mechanical allodynia induced by nerve injury or the pain initiators lysophosphatidic acid and Wnt3a. Promoting the nuclear accumulation of YAP/TAZ leads to mechanical hypersensitivity in naive animals. Further, we discovered a new small molecule, dCTB, which targets YAP/TAZ/ß-catenin and can greatly suppress neuropathic pain and the associated neurochemical alterations. Our study reveals that YAP and TAZ are core mechanisms underlying the pathogenesis of neuropathic pain and are targets in the screening for potent analgesics for the treatment of neuropathic pain. SIGNIFICANCE STATEMENT: Mechanisms that underlie neuropathic pain remain elusive. We have demonstrated recently that nerve injury can activate Wnt signaling, which becomes a trigger for the development of neuropathic pain. We report that the transcriptional regulators YAP and TAZ, which orchestrate Wnt response via incorporation in the ß-catenin destruction complex, are key in the pathogenesis of neuropathic pain and may serve as an "ON-OFF" switch for neuropathic pain status. Further, we discovered a new small molecule, dCTB, which targets YAP/TAZ/ß-catenin and can greatly suppress neuropathic pain. Our study reveals that YAP and TAZ are core mechanisms underlying the pathogenesis of neuropathic pain and are targets in the screening of potent analgesics for the treatment of neuropathic pain.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Neuralgia/prevenção & controle , Neuralgia/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/fisiopatologia , Fatores de Transcrição/metabolismo , Animais , Masculino , Neuralgia/etiologia , Medição da Dor , Percepção da Dor , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/complicações
9.
Zhonghua Zheng Xing Wai Ke Za Zhi ; 29(2): 131-5, 2013 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-23772493

RESUMO

OBJECTIVE: To investigate the effects of platelet-rich plasma (PRP) on the proliferation of dermal papilla cells (DPCs) and hair follicle regeneration. METHODS: PRP was prepared using the double-spin method and applied to DPCs. The proliferative effect of activated PRP on DPCs was measured using MTT assay. To understand the influence of activated PRP on the hair-inductive capacity of DPCs, freshly isolated epidermal cells and DPCs of passage 4 were resuspended, mixed with various concentrations of a PRP (0%, 5% or 10%) and were then transferred to a grafting chamber, which was implanted onto the dorsal skin of nude mice. The chambers were removed 1 week after grafting and HF formation was monitored for 4 weeks; the graft site was harvested and processed for histological examination. RESULTS: Activated PRP increased the proliferation benefited the aggregative growth of DPCs. There are significant difference in the yield of hair follicles compared with 10% PRP (344 +/- 27) with 0% PRP (288 +/- 35) in the area of reconstituted skin (P < 0.05). The areas treated with PRP demonstrated an increase in hair follicles density of 19.4%. Ten percent PRP (18 +/- 1) d also can significantly shorten the time of hair formation, compared with 0% PRP (20 +/- 1) d (P < 0.05). CONCLUSIONS: There is a considerable effect of PRP on the time of hair formation and the yield of hair follicles reconstitution.


Assuntos
Folículo Piloso/crescimento & desenvolvimento , Plasma Rico em Plaquetas , Pele/citologia , Animais , Proliferação de Células , Células Cultivadas , Feminino , Folículo Piloso/citologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Regeneração , Pele Artificial
10.
Behav Brain Funct ; 9: 48, 2013 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-24377651

RESUMO

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common chronic neurodevelopmental disorder with a high heritability. Much evidence of hemisphere asymmetry has been found for ADHD probands from behavioral level, electrophysiological level and brain morphology. One previous research has reported possible association between BAIAP2, which is asymmetrically expressed in the two cerebral hemispheres, with ADHD in European population. The present study aimed to investigate the association between BAIAP2 and ADHD in Chinese Han subjects. METHODS: A total of 1,397 ADHD trios comprised of one ADHD proband and their parents were included for family-based association tests. Independent 569 ADHD cases and 957 normal controls were included for case-control studies. Diagnosis was performed according to the DSM-IV criteria. Nine single nucleotide polymorphisms (SNPs) of BAIAP2 were chosen and performed genotyping for both family-based and case-control association studies. RESULTS: Transmission disequilibrium tests (TDTs) for family-based association studies showed significant association between the CA haplotype comprised by rs3934492 and rs9901648 with predominantly inattentive type (ADHD-I). For case-control study, chi-square tests provided evidence for the contribution of SNP rs4969239, rs3934492 and rs4969385 to ADHD and its two clinical subtypes, ADHD-I and ADHD-C. However, only the associations for ADHD and ADHD-I retained significant after corrections for multiplicity or logistic regression analyses adjusting the potential confounding effect of gender and age. CONCLUSIONS: These above results indicated the possible involvement of BAIAP2 in the etiology of ADHD, especially ADHD-I.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Transtorno do Deficit de Atenção com Hiperatividade/etnologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Proteínas do Tecido Nervoso/genética , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Lateralidade Funcional/genética , Marcadores Genéticos , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , Polimorfismo de Nucleotídeo Único , Adulto Jovem
11.
Zhonghua Zheng Xing Wai Ke Za Zhi ; 29(6): 448-52, 2013 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-24624885

RESUMO

OBJECTIVE: To investigate the effect of 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo. METHODS: Firstly, Hair follicles were co-cultured with 3 different concentration of 6-gingerol for 5 days and hair elongation in three groups was measured. Secondly, The proliferative effect of 6-gingerol on DPCs was measured using MTT assay. Thirdly, the expression of Bcl-2 and Bax in DPCs were measured using Western blotting. In vivo study, the influence of 6-gingerol on hair growth in C57BL/6 rats was measured through topical application of 6-gingerol on the dorsal skin of each animal. RESULTS: The length of hair shaft in 20 microg/ml 6-Gingerol group (0.50 +/- 0.08 mm) is less than 0 microg/ml (0.66 +/- 0.19) mm and 10 microg/ml (0.64 +/- 0.03) mm 6-Gingerol group (P < 0.05). In cell culture, compared to 0 microg/ml and 5 microg/ml 6-Gingerol, 10 microg/ml 6-Gingerol can significantly inhibited the proliferation of DPCs (P < 0.05). Along with the growth inhibition of DPCs by 6-gingerol, the Bax/Bcl-2 ratio increased obviously. In vivo study, the hair length and density decreased a lot after using 1 mg/ml 6-gingerol. CONCLUSIONS: 6-Gingerol can suppress human hair shaft elongation because it has pro-apoptotic effects on DPCs via increasing Bax/Bcl-2 ratio. It might inhibit hair growth by prolonging the telogen stage in vivo.


Assuntos
Catecóis/farmacologia , Álcoois Graxos/farmacologia , Folículo Piloso/efeitos dos fármacos , Cabelo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Técnicas de Cultura de Células , Células Cultivadas , Cabelo/crescimento & desenvolvimento , Folículo Piloso/crescimento & desenvolvimento , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Proteína X Associada a bcl-2/metabolismo
12.
Am J Med Genet B Neuropsychiatr Genet ; 156B(6): 730-6, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21761554

RESUMO

The cognitive deficits observed in attention deficit/hyperactivity disorder (ADHD) are candidate endophenotypes for genetic association studies. Dopamine ß-hydroxylase (DßH) converts dopamine to norepinephrine, and its activity is under strong genetic control. Prior studies suggest association between ADHD and DBH gene. The present study examined associations between a putative functional single nucleotide polymorphism (SNP) at DBH with performance on the Stroop task in patients with ADHD and in healthy control subjects. A total of 812 Han Chinese youths with DSM-IV ADHD and 233 unaffected controls were included in the study. Comprehensive phenotype data were collected, including performance on a series of Stroop interference tests examining inhibition of response to interfering stimuli. DBH SNP -1021C/T was genotyped using the 5'-exonuclease (TaqMan®) method. Compared to unaffected controls, children with ADHD performed significantly worse in all categories of the Stroop test. In ADHD cases, DBH genotype at -1021C/T significantly associates with reaction times of incongruent color word parts but not the interference times, with TT genotype performing significantly better in both reaction time and interference time than other two genotype groups. DBH genotype did not associate with cognitive performance in unaffected controls or in the combined group. DBH genotype at -1021C/T associates with differences in performance on the Stroop task in children with ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Dopamina beta-Hidroxilase/genética , Teste de Stroop , Adolescente , Criança , China , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Análise e Desempenho de Tarefas
13.
Am J Med Genet B Neuropsychiatr Genet ; 156B(6): 737-48, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21761555

RESUMO

Monoamine oxidase A (MAOA) plays a critical role in the metabolism of monoamine neurotransmitters including serotonin (5-HT), norepinephrine (NE), and dopamine (DA). Genetic studies have found an association between MAOA and attention-deficit/hyperactivity disorder (ADHD), especially impulsivity. However, there has been inconsistency among studies which may be due to the complexity and heterogeneity of ADHD, including its sexual dimorphism and the presence of several subtypes. We conducted transmission disequilibrium tests (TDTs) in 1,253 trios and found no association between five single nucleotide polymorphisms (SNPs) of MAOA with ADHD in general or in the predominantly inattentive (ADHD-I) or combined types (ADHD-C), but with the predominantly hyperactive/impulsivity type (ADHD-HI). The association with MAOA was restricted to males, especially males with ADHD-HI. Logistic regression analyses of data from 1,824 cases and 957 controls did not indicate any association. We used analysis of covariance to analyze the association between MAOA genotype with the "inhibit" factor of the Behavior Rating Inventory of Executive Function (BRIEF) in 640 probands and performance on the Stroop test in 810 probands. Probands homozygous for risk alleles found in the TDT test had higher "inhibit" scores on the BRIEF scale which represents more severe impulsivity; this results also was restricted to males. No association was found with Stroop test performance. In conclusion, our results provide some evidence that MAOA may be associated with the ADHD-HI subtype and support the association between MAOA and impulsivity, which may be a potential endophenotype of ADHD. However, the results were strongly influenced by gender.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Predisposição Genética para Doença , Comportamento Impulsivo/genética , Monoaminoxidase/genética , Adolescente , Estudos de Casos e Controles , Criança , China , Feminino , Genótipo , Haplótipos/genética , Humanos , Masculino , Neurotransmissores/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Teste de Stroop
14.
Zhongguo Zhong Yao Za Zhi ; 31(7): 570-3, 2006 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-16780161

RESUMO

OBJECTIVE: To study the protective effects of curcumin on exaggerated extracellular matrix accumulation of pulmonary fibrosis rats. METHOD: One hundred and forty-four male Sprague-Dawley rats were randomly divided into 6 groups (24 rats in each group). Rats in the model control group, positive medicine group, and high, moderate and low curcumin groups were injected with a single dose of bleomycin by trachea, and rats in sham-model control group with same volume normal saline. One day after the injection, curcumin solution of different dosages (200, 100, 50 mg x kg(-1) x d(-1)) was respectively given to rats in the high, moderate and low curcumin group daily by gastrogavage, while equal volume of normal saline was given to those in the sham-model control group and model control group, and an equal volume of prednisone (0.56 mg x kg(-1) x d(-1)) was given to those in positive medicine control group. On the 7, 14, 28 days, 8 rats per treatment group were randomly killed, the levels of III-collagen, IV-collagen, laminin and hyaluronic acid in the serum were determined, the determination of hydroxyproline in lung homogenates was analyzed, and the lung was incised to make pathological sections which were stained with HE and Mallory. RESULT: Curcumin could decreas the levels of III-collagen, IV-collagen, laminin and hyaluronic acid in the serum, and inhihit the proliferation of fibrous tissue. CONCLUSION: Curcumin may play its therapetuic role by leveling down the content of extracellular matrix in rats with pulmonary fibrosis induced by bleomycin.


Assuntos
Curcuma , Curcumina/farmacologia , Proteínas da Matriz Extracelular/sangue , Fibrose Pulmonar/metabolismo , Animais , Bleomicina , Peso Corporal/efeitos dos fármacos , Colágeno Tipo III/sangue , Colágeno Tipo IV/sangue , Curcuma/química , Curcumina/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Proteínas da Matriz Extracelular/metabolismo , Ácido Hialurônico/sangue , Hidroxiprolina/sangue , Hidroxiprolina/metabolismo , Laminina/sangue , Pulmão/metabolismo , Pulmão/patologia , Masculino , Plantas Medicinais/química , Substâncias Protetoras/farmacologia , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
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