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1.
BMC Neurol ; 21(1): 398, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645398

RESUMO

BACKGROUND: The significance of carotid webs (CaWs) in ischemic stroke is becoming acknowledged. Histological features of clot composition in situ and secondary cerebrovascular embolized thrombi caused by CaW have not been described concurrently. Understanding clots' histological composition is essential for understanding the pathophysiology of clot formation in CaW. CASE PRESENTATION: A 50-year-old male patient with acute ischemic stroke, which was believed to be caused by ipsilateral CaW, was admitted to the hospital. Mechanical thrombectomy was used to retrieve thromboemboli from the middle cerebral artery. One month thereafter, the patient underwent carotid endarterectomy, and in situ CaW thrombi were retrieved. Histological analysis by hematoxylin and eosin staining revealed that histopathologic embolized thrombi appeared as typical mixed thrombi, 46.03% fibrin/platelet ratio, 48.12% RBCs, and 5.85% white blood cells. In situ thrombi had a higher fibrin/platelet ratio (68.0%), fewer RBCs (17.2%), and 14.8% white blood cells. CONCLUSION: The histopathology of large vessel occlusion stroke embolized thrombi by CaW is similar to that of other stroke etiologies. However, the clot composition of embolized thrombi significantly differs from that of in situ thrombi. CaW's in situ thrombi showed predominantly fibrin, and embolized thrombi had equivalent contents of red blood cells and fibrin/platelets. Histopathological differences between in situ and embolized thrombi suggest new research directions for the etiology of embolization. Further studies are required to confirm these results.

2.
Int J Mol Sci ; 22(16)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34445457

RESUMO

Strigolactones (SLs) regulate plant shoot development by inhibiting axillary bud growth and branching. However, the role of SLs in wintersweet (Chimonanthus praecox) shoot branching remains unknown. Here, we identified and isolated two wintersweet genes, CCD7 and CCD8, involved in the SL biosynthetic pathway. Quantitative real-time PCR revealed that CpCCD7 and CpCCD8 were down-regulated in wintersweet during branching. When new shoots were formed, expression levels of CpCCD7 and CpCCD8 were almost the same as the control (un-decapitation). CpCCD7 was expressed in all tissues, with the highest expression in shoot tips and roots, while CpCCD8 showed the highest expression in roots. Both CpCCD7 and CpCCD8 localized to chloroplasts in Arabidopsis. CpCCD7 and CpCCD8 overexpression restored the phenotypes of branching mutant max3-9 and max4-1, respectively. CpCCD7 overexpression reduced the rosette branch number, whereas CpCCD8 overexpression lines showed no phenotypic differences compared with wild-type plants. Additionally, the expression of AtBRC1 was significantly up-regulated in transgenic lines, indicating that two CpCCD genes functioned similarly to the homologous genes of the Arabidopsis. Overall, our study demonstrates that CpCCD7 and CpCCD8 exhibit conserved functions in the CCD pathway, which controls shoot development in wintersweet. This research provides a molecular and theoretical basis for further understanding branch development in wintersweet.


Assuntos
Arabidopsis , Calycanthaceae/genética , Dioxigenases , Genes de Plantas , Proteínas de Plantas , Raízes de Plantas , Plantas Geneticamente Modificadas , Arabidopsis/enzimologia , Arabidopsis/genética , Calycanthaceae/enzimologia , Dioxigenases/biossíntese , Dioxigenases/genética , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Raízes de Plantas/enzimologia , Raízes de Plantas/genética , Plantas Geneticamente Modificadas/enzimologia , Plantas Geneticamente Modificadas/genética
3.
Nutrients ; 13(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33477648

RESUMO

In an aging society, preventing dysfunction and restoring function of the locomotive organs are necessary for long-term quality of life. Few interventional studies have investigated supplementation for locomotive syndrome. Additionally, very few interventional clinical studies on locomotive syndrome have been performed as placebo-controlled, randomized, double-blind studies. We previously found that the administration of 30% ethanolic extract of Cistanche tubulosa improved walking ability in a cast-immobilized skeletal muscle atrophy mouse model. Therefore, we conducted a clinical study to evaluate the effects of C. tubulosa (CT) extract on the locomotive syndrome. Twenty-six subjects with pre-symptomatic or mild locomotive syndrome completed all tests and were analyzed in the study. Analyses of muscle mass and physical activity were performed based on the full analysis set. Intake of CT extract for 12 weeks increased step width (two-step test) and gait speed (5 m walking test) in patients over 60 years old compared with those in a placebo control (p = 0.046). In contrast, the skeletal muscle mass of the body trunk and limbs was unchanged following administration of CT extract. Adverse effects were evaluated by blood tests; no obvious adverse events were observed following the intake of CT extract. In conclusion, this placebo-controlled, randomized, double-blind study demonstrated that treatment with CT extract significantly prevented a decline in walking ability without any notable adverse effects in patients with locomotive syndrome.


Assuntos
Cistanche/química , Transtornos Neurológicos da Marcha/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Idoso , Cistanche/efeitos adversos , Método Duplo-Cego , Exercício Físico , Feminino , Transtornos Neurológicos da Marcha/fisiopatologia , Transtornos Neurológicos da Marcha/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Fitoterapia , Placebos , Extratos Vegetais/efeitos adversos , Qualidade de Vida , Caminhada/fisiologia
4.
J Nat Med ; 75(1): 207-216, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32979168

RESUMO

Several studies have suggested that some kind of Dioscorea species (yam) or yam-contained herbal medicines have cognitive enhancement effect. However, it has been unknown what is a crucial factor for cognitive enhancement in each Dioscorea species. In this study, we aimed to investigate whether one of the main and brain-penetrating components in yams, diosgenin, can be a novel criterion to assess memory enhancement effect of yam extracts. Although our previous studies showed that administration of diosgenin or diosgenin-rich yam extract enhanced cognitive function in normal mice and healthy humans, we have never evaluated whether the effect depends on diosgenin content or not. Therefore, we compared memory enhancement effects of low diosgenin-contained general yam water extract with diosgenin-rich yam extract on cognitive function in normal mice. We found that unlike diosgenin-rich yam, administration of general yam water extract did not enhance object recognition memory in normal mice. LC-MS/MS analyses revealed that after administration of general yam, diosgenin concentration in the brain did not reach to the effective dose because of the low diosgenin content in the original yam extract. On the other hand, when diosgenin was artificially added into general yam, the extract showed memory enhancement in normal mice and promoted neurite outgrowth in neurons. Our study suggests that diosgenin is actually an active compound in yams for memory enhancement, and diosgenin content can be a criterion for predicting cognitive enhancement effect of yam extracts.


Assuntos
Cognição/efeitos dos fármacos , Dioscorea/química , Diosgenina/uso terapêutico , Memória/efeitos dos fármacos , Extratos Vegetais/química , Animais , Diosgenina/farmacologia , Humanos , Camundongos , Estrutura Molecular
5.
Sci Rep ; 10(1): 16424, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009465

RESUMO

Trigonelline (TGN; 1-methylpyridin-1-ium-3-carboxylate) is a widely distributed alkaloid derived from plants. Since we previously found a neurite outgrowth effect of TGN, we hypothesised that TGN might help to improve memory deficits. Here, the efficacy of TGN in restoring amyloid ß (Aß)-induced axonal degeneration and in improving memory function was investigated in Alzheimer's disease 5XFAD model mice that overexpress mutated APP and PS1 genes. Exposure of Aß25-35 for 3 days induced atrophy of axons and dendrites. Post treatment of TGN recovered the lengths of axons and dendrites. Following oral administration of TGN in mice, TGN itself was detected in the plasma and cerebral cortex. Oral administration of TGN to 5XFAD mice for 14 days showed significant improvement in object recognition memory (P < 0.001) and object location memory (P < 0.01). TGN administration also normalised neurofilament light levels in the cerebral cortex (P < 0.05), which is an axonal damage-associated biomarker. Analysis of target proteins of TGN in neurons by a drug affinity responsive target stability (DARTS) method identified that creatine kinase B-type (CKB) is a direct binding protein of TGN. Treatment with a CKB inhibitor cancelled the TGN-induced axonal and dendritic growth. In conclusion, we found for the first time that TGN penetrates the brain and may activate CKB, leading to axonal formation. This study shows the potential of TGN as a new drug candidate, and a new target molecule, CKB, in memory recovery signalling.


Assuntos
Alcaloides/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Córtex Cerebral/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Memória/efeitos dos fármacos , Alcaloides/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Atrofia/tratamento farmacológico , Atrofia/metabolismo , Axônios/efeitos dos fármacos , Axônios/metabolismo , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Feminino , Transtornos da Memória/metabolismo , Camundongos , Camundongos Transgênicos/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fragmentos de Peptídeos/metabolismo
6.
Cerebrovasc Dis ; 49(4): 382-387, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756062

RESUMO

INTRODUCTION: Safety of carotid artery stenting (CAS) in patients having carotid stenosis with coexistent unruptured intracranial aneurysms (UIAs) is rarely reported. Thus, we studied the 3-month outcome of CAS in the presence of coexistent UIAs in our institution. METHODS: A retrospective analysis of patients receiving CAS at our institution from September 2011 to December 2019 was carried out. Patients were stratified into 2 groups: group of CAS with UIAs (CAS-UIA) and group of CAS without UIAs (CAS). The main complications within 3 months after stenting were TIA, ischemic stroke, symptomatic intracranial hemorrhage (sICH), rupture of UIAs, and death. The baseline characteristics and complications of the 2 groups were compared. RESULTS: Five hundred fifty-six patients (CAS, n = 468; CAS-UIA, n = 88) were included and 604 stenting procedures were performed. More patients had hypertension in the CAS-UIA group (87.5 vs. 73.7%, p = 0.006). There was no significant difference in TIAs, ischemic stroke, sICH, and death within 3 months after stenting between the CAS and CAS-UIA groups. None of the 113 coexistent UIAs detected in 88 patients had aneurysm rupture within 3 months after CAS. CONCLUSIONS: In our large cohort of CAS patients, coexistent UIAs are not uncommon. Stenting of a carotid artery in the presence of coexistent UIAs could be conducted safely. Together with 3-month dual antiplatelet therapy, CAS did not increase the rupture risk of the coexistent UIAs within 3 months.


Assuntos
Estenose das Carótidas/terapia , Procedimentos Endovasculares/instrumentação , Aneurisma Intracraniano/complicações , Stents , Idoso , Aneurisma Roto/etiologia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/mortalidade , Terapia Antiplaquetária Dupla , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/mortalidade , Hemorragias Intracranianas/etiologia , Ataque Isquêmico Transitório/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento
7.
Int J Mol Sci ; 21(13)2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32630004

RESUMO

In Alzheimer's disease (AD), amyloid ß (Aß) induces axonal degeneration, neuronal network disruption, and memory impairment. Although many candidate drugs to reduce Aß have been clinically investigated, they failed to recover the memory function in AD patients. Reportedly, Aß deposition occurred before the onset of AD. Once neuronal networks were disrupted by Aß, they could hardly be recovered. Therefore, we speculated that only removal of Aß was not enough for AD therapy, and prevention and recovery from neuronal network disruption were also needed. This review describes the challenges related to the condition of axons for AD therapy. We established novel in vitro models of Aß-induced axonal degeneration. Using these models, we found that several traditional medicines and their constituents prevented or helped recover from Aß-induced axonal degeneration. These drugs also prevented or helped recover from memory impairment in in vivo models of AD. One of these drugs ameliorated memory decline in AD patients in a clinical study. These results indicate that prevention and recovery from axonal degeneration are possible strategies for AD therapy.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Axônios/efeitos dos fármacos , Magnoliopsida , Fitoterapia , Extratos Vegetais/uso terapêutico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Axônios/metabolismo , Células Cultivadas , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Extratos Vegetais/farmacologia
8.
Nutrients ; 12(2)2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31979283

RESUMO

We previously found that the water extract of Eleutherococcus senticosus leaves (ES extract) enhanced cognitive function in normal mice. Our study also revealed that the water extract of rhizomes of Drynaria fortunei (DR extract) enhanced memory function in Alzheimer's disease model mice. In addition, our previous experiments suggested that a combined treatment of ES and DR extracts synergistically improved memory and anti-stress response in mice. Although those two botanical extracts are expected to be beneficial for neuropsychological function, no clinical data has ever been reported. Therefore, we performed a placebo-controlled, randomized, double-blind study to evaluate cognitive enhancement and anti-stress effects by the intake of a combined extract in healthy volunteers. The intake period was 12 weeks. The Japanese version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test was used for neurocognitive assessment. The combined treatment of ES and DR extracts significantly increased the figure recall subscore of RBANS (p = 0.045) in an intergroup comparison. Potentiation of language domain ((p = 0.040), semantic fluency (p = 0.021) and figure recall (p = 0.052) was shown by the extracts (in intragroup comparison). In anti-stress response, the anxiety/uncertainly score was improved by the extract in an intragroup comparison (p = 0.022). No adverse effects were observed. The combined treatment of ES and DR extracts appear to safely enhance a part of cognitive function in healthy adults.


Assuntos
Cognição/efeitos dos fármacos , Eleutherococcus , Nootrópicos/administração & dosagem , Extratos Vegetais/administração & dosagem , Polypodiaceae , Idoso , Método Duplo-Cego , Eleutherococcus/química , Feminino , Voluntários Saudáveis , Humanos , Japão , Masculino , Rememoração Mental/efeitos dos fármacos , Pessoa de Meia-Idade , Nootrópicos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Polypodiaceae/química , Rizoma , Solventes/química , Água/química
9.
Nutrients ; 11(5)2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31121888

RESUMO

The pharmacological properties of Eleutherococcus senticosus leaf have not been clarified although it is taken as a food item. In this study, the effects of water extract of Eleutherococcus senticosus leaves on memory function were investigated in normal mice. Oral administration of the extract for 17 days significantly enhanced object recognition memory. Compounds absorbed in blood and the brain after oral administration of the leaf extract were detected by LC-MS/MS analyses. Primarily detected compounds in plasma and the cerebral cortex were ciwujianoside C3, eleutheroside M, ciwujianoside B, and ciwujianoside A1. Pure compounds except for ciwujianoside A1 were administered orally for 17 days to normal mice. Ciwujianoside C3, eleutheroside M, and ciwujianoside B significantly enhanced object recognition memory. These results demonstrated that oral administration of the leaf extract of E. senticosus enhances memory function, and that active ingredients in the extract, such as ciwujianoside C3, eleutheroside M, and ciwujianoside B, were able to penetrate and work in the brain. Those three compounds as well as the leaf extract had dendrite extension activity against primary cultured cortical neurons. The effect might relate to memory enhancement.


Assuntos
Encéfalo/efeitos dos fármacos , Eleutherococcus/química , Memória/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Células Cultivadas , Córtex Cerebral/química , Córtex Cerebral/embriologia , Córtex Cerebral/ultraestrutura , Dendritos/efeitos dos fármacos , Dendritos/fisiologia , Glicosídeos/análise , Glicosídeos/farmacocinética , Glicosídeos/farmacologia , Masculino , Camundongos , Extratos Vegetais/análise , Extratos Vegetais/farmacocinética , Saponinas/análise , Saponinas/farmacocinética , Saponinas/farmacologia
10.
J Reconstr Microsurg ; 35(7): 499-504, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30836413

RESUMO

BACKGROUND: End-to-end, end-to-side, and side-to-side microvascular anastomoses are the main types of vascular bypass grafting used in microsurgery and neurosurgery. Currently, there has been no animal model available for practicing all three anastomoses in one operation. The aim of this study was to develop a novel animal model that utilizes the rat abdominal aorta (AA), common iliac arteries (CIAs), and the median sacral artery (MSA) for practicing these three types of anastomosis. METHODS: Eight adult Sprague-Dawley rats were anesthetized and then laparotomized. The AA, MSA, and bilateral CIAs were exposed and separated from the surrounding tissues. The length and diameter of each artery were measured. The relatively long segment of the AA without major branches was selected to perform end-to-end anastomosis. One side of the CIAs (or AA) and MSA were used for end-to-side anastomosis. The bilateral CIAs were applied to a side-to-side and another end-to-side anastomosis. RESULTS: Anatomical dissection of the AA, CIAs, and MSA was successfully performed on eight Sprague-Dawley rats; four arterial-to-arterial anastomoses were possible for each animal. The AA trunk between the left renal artery and right iliolumbar arteries was 15.60 ± 0.76 mm in length, 1.59 ± 0.15 mm in diameter, for an end-to-end anastomosis. The left CIA was 1.06 ± 0.08 mm in diameter, for an end-to-side anastomosis with the right CIA. The MSA was 0.78 ± 0.07 mm in diameter, for another end-to-side anastomosis with the right CIA or AA. After finishing end-to-side anastomosis in the proximal part of bilateral CIAs, the distal portion was juxtaposed for an average length of 5.6 ± 0.25 mm, for a side-to-side anastomosis. CONCLUSION: This model can comprehensively and effectively simulate anastomosis used in revascularization procedures and can provide more opportunities for surgical education, which may lead to more routine use in microvascular anastomosis training.


Assuntos
Anastomose Cirúrgica/educação , Microcirurgia/educação , Procedimentos Cirúrgicos Vasculares/educação , Animais , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley
12.
J Pain ; 20(4): 394-404, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30219729

RESUMO

Fewer randomized clinical trials (RCTs) are conducted for chronic or recurrent pain in pediatric populations compared with adult populations; thus, data to support treatment efficacy in children are limited. This article evaluates the design features and reporting practices of RCTs for chronic and recurrent pain that are likely unique to, or particularly important in, a pediatric population to promote improvements in the evidence base for pediatric pain treatments. Areas covered include outcome measure selection and reporting and reporting of adverse events and challenges to recruitment and retention. A search of PubMed and EMBASE identified primary publications describing RCTs of treatments for select chronic and recurrent pain conditions in children or adolescents published between 2000 and 2017. Only 49% of articles identified a primary outcome measure. The primary outcome measure assessed pain intensity in 38% of the trials, specifically measure by verbal rating scale (13%), faces pain scale (11%), visual analogue scale (9%), or numeric rating scale (5%). All of the CONSORT harms reporting recommendations were fulfilled by <50% of the articles. Discussions of recruitment challenges occurred in 64% of articles that enrolled <90% of their target sample. However, discussions regarding retention challenges only occurred in 14% of trials in which withdrawal rates were >10%. The goal of this article is to promote comprehensive reporting of pediatric pain RCTs to improve the design of future trials, facilitate conduction of systematic reviews and meta-analyses, and better inform clinical practice. PERSPECTIVE: This review of chronic and recurrent pediatric pain trials demonstrates inadequacies in the reporting quality of key features specifically important to pediatric populations. It provides recommendations that address these shortcomings to promote continued efforts toward improving the quality of the design and publication of future pediatric clinical pain trials.


Assuntos
Ensaios Clínicos como Assunto , Metanálise em Rede , Avaliação de Resultados em Cuidados de Saúde , Manejo da Dor , Dor , Pediatria , Projetos de Pesquisa , Criança , Humanos
13.
J Clin Neurosci ; 59: 112-118, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30401573

RESUMO

Drug-eluting stent (DES) is a potential endovascular treatment for patients with symptomatic intracranial atherosclerotic disease (sICAD). However, evidence regarding the treatment of ICAD with DES is lacking. We systematically searched Pubmed, Embase, Cochrane database (before 2017-12-21) for literature reporting the application of DES in the treatment of sICAD. The main outcomes were as follows: the incidence of any stroke or death within 30 days (perioperative complications), ischemic stroke in the territory of the qualifying artery beyond 30 days (long-term complications), in-stent restenosis rate (ISR) and symptomatic ISR during follow-up. Those studies with mean stenosis rate greater than 70% and less than 70% were defined as severe and moderate stenosis group, respectively. The random effect model was used to pool the data. Of 518 articles, 13 studies were eligible and included in our analysis (N = 336 patients with 364 lesions). After the implantation of DES, perioperative complications (mortality = 0) occurred in 6.0% (95%CI 2.0%-11.9%), long-term complications occurred in 2.2% (95%CI 0.7%-4.5%), ISR rate was 4.1% (95%CI 1.6%-7.7%) and the symptomatic ISR rate was only 0.5% (95%CI 0-2.2%). In addition, subgroup analysis showed that the perioperative complication rate in severe stenosis group [10.6% (95%CI 6.5%-15.7%)] was significantly (p < 0.01) higher than that in moderate stenosis group [1.0% (95%CI 0.3%-3.5%)]. In summary, endovascular DES implantation is a relatively safe and effective method compared with stents or medical management group in SAMMPRIS and VISSIT trials. However, a higher preoperative stenosis rate may imply a higher risk of perioperative complications. Further studies are needed.


Assuntos
Stents Farmacológicos , Arteriosclerose Intracraniana/terapia , Idoso , Stents Farmacológicos/efeitos adversos , Procedimentos Endovasculares/métodos , Feminino , Humanos , Incidência , Arteriosclerose Intracraniana/complicações , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
14.
Sci Rep ; 8(1): 11707, 2018 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-30076345

RESUMO

We previously found diosgenin, an herbal drug-derived steroid sapogenin, to be remarkably effective at restoring Aß-induced axonal degeneration and improving memory function in model of Alzheimer's disease (AD), 5XFAD mouse. In this study, we investigated the downstream signaling of diosgenin and explored new therapeutic targets in AD. We showed that the expression of heat shock cognate (HSC) 70 was increased in Aß-treated neurons and in 5XFAD mice but was decreased by diosgenin treatment. In addition, knockdown of HSC70 significantly promoted axonal growth in neurons. As an association molecule of HSC70 in neurons, α-tubulin was detected by immunoprecipitation. After Aß treatment, α-tubulin expression was greatly reduced in the degenerated axons, suggesting that a decline in α-tubulin may be one of the factors which correlates with axonal disruption in AD pathology. We hypothesized that the degradation of α-tubulin is triggered by the chaperone activity of HSC70. However, diosgenin significantly normalized the α-tubulin level, a potentially critical process for axonal formation. Our study indicated that reducing the HSC70 level is a new possible therapeutic target of axonal regeneration in AD.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Axônios/patologia , Diosgenina/uso terapêutico , Regulação da Expressão Gênica , Proteínas de Choque Térmico HSC70/genética , Degeneração Neural/tratamento farmacológico , Degeneração Neural/genética , Animais , Axônios/efeitos dos fármacos , Córtex Cerebral/patologia , Diosgenina/administração & dosagem , Diosgenina/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSC70/metabolismo , Masculino , Camundongos Transgênicos , Isomerases de Dissulfetos de Proteínas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tubulina (Proteína)/metabolismo
16.
J Clin Neurosci ; 52: 41-49, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29550249

RESUMO

Carotid stenosis (CS) and intracranial aneurysms (IAs) may concur in one person. We studied the prevalence of IAs in CS patients in our retrospectively collected database and systematically reviewed this issue. Five hundred and fifty-seven CS (≥50%) patients confirmed by DSA in our hospital from 2010-06 to 2015-06 were screened for coexistent IAs. After searching the related literatures from English and Chinese journal literature databases, a meta-analysis was performed to pool the prevalence of CS with coexistent IAs. Subgroup analyses were performed to explore the causes of heterogeneity among studies. IAs were detected in 98(17.0%) out of the 577 CS patients. 12 literatures and the present study including a total of 6965 CS patients and 446 cases with coexistent IAs. The pooled prevalence of CS with coexistent IAs was 6.3% (95%CI: 4.2-8.3%) in all the CS patients. The pooled RR for female to male CS patients to have coexistent IAs was 1.67 (95%CI: 1.34-2.08, P = 0.000). 3 studies and the present study were carried out in Asian countries with a pooled prevalence of 10.8% (95%CI: 5.3-16.3%); 6 studies in European countries with 3.0% (95%CI: 2.2-3.7%); and 3 studies in USA with 6.0% (95%CI: 2.2-9.7%). There was a statistically significant difference between the three subgroups (P < 0.001). The prevalence of IAs in CS patients seems higher in our clinical study and the meta-analysis than in the general population and previously reported. The eastern and the women CS patients have a higher risk for coexistent IAs.


Assuntos
Estenose das Carótidas/complicações , Estenose das Carótidas/epidemiologia , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/epidemiologia , Adulto , Idoso , Ásia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
17.
Front Pharmacol ; 9: 48, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29441022

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disorder resulting in structural brain changes and memory impairment. We hypothesized that reconstructing neural networks is essential for memory recovery in AD. Heat shock cognate 70 (HSC70), a member of the heat shock protein family of molecular chaperones, is upregulated in AD patient brains, and recent studies have demonstrated that HSC70 facilitates axonal degeneration and pathological progression in AD. However, the direct effects of HSC70 inhibition on axonal development and memory function have never been investigated. In this study, we examined the effects of a small-molecule HSC70 inhibitor, VER-155008, on axonal morphology and memory function in a mouse model of AD (5XFAD mice). We found that VER-155008 significantly promoted axonal regrowth in amyloid ß-treated neurons in vitro and improved object recognition, location, and episodic-like memory in 5XFAD mice. Furthermore, VER-155008 penetrated into the brain after intraperitoneal administration, suggesting that VER-155008 acts in the brain in situ. Immunohistochemistry revealed that VER-155008 reduced bulb-like axonal swelling in the amyloid plaques in the perirhinal cortex and CA1 in 5XFAD mice, indicating that VER-155008 also reverses axonal degeneration in vivo. Moreover, the two main pathological features of AD, amyloid plaques and paired helical filament tau accumulation, were reduced by VER-155008 administration in 5XFAD mice. This is the first report to show that the inhibition of HSC70 function may be critical for axonal regeneration and AD-like symptom reversal. Our study provides evidence that HSC70 can be used as a new therapeutic target for AD treatment.

18.
Front Neurol ; 8: 508, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28993755

RESUMO

BACKGROUND: Extracranial internal carotid artery (eICA) tortuosity may trigger cerebral ischemia, and body mass index (BMI) is a measure of body mass based on height and weight. The main purpose of this study is to determine the influence of BMI on the tortuosity of eICA. METHODS: A total of 926 carotid artery angiograms were performed in 513 patients, of which 116 cases and matched controls were selected. Arterial tortuosity was defined as simple tortuosity, kinking, or coiling. The severity of tortuosity was measured by tortuosity index, formula: [(actual length/straight-line length - 1) × 100]. RESULTS: BMIs were different between the two groups [tortuosity: 27.06 kg/m2 (SD 2.81 kg/m2) versus none: 23.3 kg/m2 (SD 2.78 kg/m2); p < 0.001]. BMI was independently and significantly associated with eICA tortuosity (odds ratio 1.59; 95% confidence interval, 1.35-1.86; p < 0.001). eICA tortuosity index is linearly associated with BMI (exponential coefficient ß = 1.067, p < 0.001). The optimal predictive threshold of BMI for eICA tortuosity was 25.04 kg/m2. The physiological mechanism underlying the reasons why higher BMI has negative influence on extracranial carotid artery tortuosity may be an intra-abdominal hypertension caused by a much higher amount of body fat stored in visceral adipose tissue. CONCLUSION: Our result reveals a novel role for greater BMI on the presence of eICA tortuosity. For each increase in BMI of 1 kg/m2, there is a corresponding 1.59-fold increase in the risk of developing eICA tortuosity. The severity of eICA tortuosity increases linearly with increased BMI.

19.
Nutrients ; 9(10)2017 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-29064406

RESUMO

Diosgenin, a yam-derived compound, was found to facilitate the repair of axonal atrophy and synaptic degeneration and improve memory dysfunction in a transgenic mouse model of Alzheimer's disease (AD). It was also found to enhance neuronal excitation and memory function even in normal mice. We hypothesized that diosgenin, either isolated or in an extract, may represent a new category of cognitive enhancers with essential activities that morphologically and functionally reinforce neuronal networks. This study aimed to investigate the effects of a diosgenin-rich yam extract on cognitive enhancement in healthy volunteers. For this placebo-controlled, randomized, double-blind, crossover study, 28 healthy volunteers (age: 20-81 years) were recruited from Toyama Prefecture, Japan, and was randomly assigned to receive either a yam extract or placebo. Preliminary functional animal experiments indicated that an oil solvent mediated the most efficient distribution of diosgenin into the blood and brain after oral administration, and was a critical factor in the cognitive benefits. Therefore, test samples (placebo and yam extract) were prepared with olive oil and formulated as soft capsules. The intake period was 12 weeks, and a 6-week washout period separated the two crossover intake periods. The Japanese version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test was used for neurocognitive assessment, and the adverse effects were monitored through blood testing. Diosgenin-rich yam extract consumption for 12 weeks yielded significant increases in total RBANS score. Among the 12 individual standard cognitive subtests, diosgenin-rich yam extract use significantly improved the semantic fluency. No adverse effects were reported. The diosgenin-rich yam extract treatment appeared to safely enhance cognitive function in healthy adults.


Assuntos
Cognição/efeitos dos fármacos , Dioscorea/química , Diosgenina/farmacologia , Extratos Vegetais/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Glicemia/metabolismo , Colesterol/sangue , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Adulto Jovem
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