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1.
Medicine (Baltimore) ; 99(35): e22035, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871960

RESUMO

Imbalances in the gut microbiota mediate the progression of neurodegenerative diseases such as Parkinson's disease (PD). Fecal microbiota transplantation (FMT) is currently being explored as a potential therapy for PD. The objective of this study was to assess the efficacy and safety of FMT on PD. Fifteen PD patients were included, 10 of them received FMT via colonoscopy (colonic FMT group) and 5 received FMT via nasal-jejunal tube (nasointestinal FMT group). The score of PSQI, HAMD, HAMA, PDQ-39, NMSQ and UPDRS-III significantly decreased after FMT treatment (all P < .05). Colonic FMT group showed significant improvement and longer maintenance of efficacy compared with nasointestinal FMT (P = .002). Two patients achieved self-satisfying outcomes that last for more than 24 months. However, nasointestinal FMT group had no significant therapeutic effect, although UPDRS-III score slightly reduced. There were no patients were satisfied with nasointestinal FMT for more than 3 months. Among 15 PD patients, there were 5 cases had adverse events (AEs), including diarrhea (2 cases), abdominal pain (2 cases) and flatulence (1 case). These AEs were mild and self-limiting. We conclude that FMT can relieve the motor and non-motor symptoms with acceptable safety in PD. Compared with nasointestinal FMT, colonic FMT seems better and preferable.


Assuntos
Transplante de Microbiota Fecal/estatística & dados numéricos , Doença de Parkinson/terapia , Idoso , Colonoscopia , Transplante de Microbiota Fecal/efeitos adversos , Transplante de Microbiota Fecal/métodos , Feminino , Humanos , Intubação Gastrointestinal , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Projetos Piloto , Adulto Jovem
2.
Exp Ther Med ; 16(4): 3680-3685, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30233726

RESUMO

A number of studies indicated that apoptosis, a specific type of programmed cell death, contributed to the loss of dopaminergic neurons during progression of Parkinson's disease (PD). Previously, the authors of the present study demonstrated that apoptosis of dopaminergic neurons was mainly achieved via the mitochondria-mediated apoptosis pathway, however, the precise molecular mechanisms remain to be elucidated. The present study aimed to determine whether mitofusin-2 (MFN2), a mitochondrial protein, participated in the apoptosis of dopaminergic neurons in a cellular model of PD induced by rotenone. The present study demonstrated that the expression of MFN2 was relatively stable following treatment with rotenone. Lentiviral knockdown and overexpression experiments for the first time, to the best of the authors knowledge, revealed that MFN2 prevented rotenone-induced cell death by amelioration of apoptosis. These results revealed a protective role of MFN2 against apoptosis in an in vitro model of PD and may be used to establish MFN2 as a potential therapeutic target for the treatment of this disease.

3.
Aging (Albany NY) ; 10(4): 645-657, 2018 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-29667931

RESUMO

During the aging process, chronic neuroinflammation induced by microglia is detrimental for the brain and contributes to the etiology of several aging-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. As a newly identified axis of renin-angiotensin system, ACE2/Ang-(1-7)/MAS1 axis plays a crucial role in modulating inflammatory responses under various pathological conditions. However, its relationship with aging-related neuroinflammation is less studied so far. In this study, by using SAMP8 mice, an animal model of accelerated aging, we revealed that the neuroinflammation in the aged brain might be attributed to a decreased level of Ang-(1-7). More importantly, we provided evidence that AVE0991, a nonpeptide analogue of Ang-(1-7), attenuated the aging-related neuroinflammation via suppression of microglial-mediated inflammatory response through a MAS1 receptor-dependent manner. Meanwhile, this protective effect might be ascribed to the M2 activation of microglia induced by AVE0991. Taken together, these findings reveal the association of Ang-(1-7) with the inflammatory response in the aged brain and uncover the potential of its nonpeptide analogue AVE0991 in attenuation of aging-related neuroinflammation.


Assuntos
Envelhecimento/metabolismo , Angiotensina I/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Imidazóis/farmacologia , Fragmentos de Peptídeos/metabolismo , Envelhecimento/efeitos dos fármacos , Animais , Encéfalo/patologia , Inflamação/metabolismo , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo
4.
Biomed Mater Eng ; 28(4): 393-400, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28869425

RESUMO

OBJECTIVE: This study aims to explore the application prospect of low oxygen dead space ventilation (LODSV) in evaluating vasomotor reactivity (VMR) by comparison between LODSV and breath-holding test (BHT). METHODS: Outpatient or inpatient patients who underwent transcranial Doppler sonography (TCD) were enrolled into this study. These patients successively underwent BHT and LODSV. The cooperation degree, tolerance conditions and adverse reactions in patients were recorded, and VMR was calculated, compared and analyzed. RESULTS: Patients had poor cooperation during BHT. Except for compensatory tachypnea after BHT, patients basically had no adverse reaction. The main manifestations of patients undergoing LODSV were deepened breathing and accelerated frequency in the end of the ventilation, and increased heart rate and a slight decline in pulse oxygen that rapidly recovered after ventilation. The increase rate of blood flow velocity in patients undergoing LODSV was significantly higher than in BHT (P<0.001), and its calculated VMR value was approximately 15% higher than BHT (P<0.001). BHT revealed a monophasic curve that slightly descends and rapidly increases, and LODSV revealed a curve that descends for a short time and slowly increases with a platform. CONCLUSION: LODSV can effectively eliminate the affect of poor cooperation in patients, and avoid intolerance caused by hypoxia. Hence, VMR value is more accurate than that determined by BHT; and this can reflect the maximum reaction ability of the blood vessels. Therefore, this method has higher clinical application value.


Assuntos
Suspensão da Respiração , Circulação Cerebrovascular , Oxigênio/fisiologia , Sistema Vasomotor , Velocidade do Fluxo Sanguíneo , Humanos , Hipóxia , Ultrassonografia Doppler Transcraniana
5.
Neurosci Lett ; 644: 94-99, 2017 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-28223160

RESUMO

Parkinson's disease (PD) is a progressive age-related debilitating motor disorder and the second most common neurodegenerative disease after Alzheimer's disease. In this study, we aimed to investigate the expression of 24 candidate miRNAs in PD and to assess their diagnostic value in patients with PD. We collected serum samples from 109 patients with PD and 40 age- and sex-matched healthy volunteers (control group). RNAs encapsulated in exosome-like microvesicles in serum were extracted and reverse transcribed. Serum miRNAs were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the ability of the miRNAs to accurately discriminate PD was analyzed by receiver operating characteristic curves. Based on our analysis, we further validated the downregulation of miR-19b and the upregulation of miR-195 and miR-24 in patients with PD. When compared with the control group, the area under the curve (AUC) values for miR-19b, miR-24, and miR-195 were 0.753, 0.908, and 0.697, respectively. Therefore, analysis of the expression levels of miR-19b, miR-24, and miR-195 in serum may be useful for the diagnosis of PD.


Assuntos
Biomarcadores/sangue , MicroRNAs/sangue , Doença de Parkinson/sangue , Idoso , Área Sob a Curva , Micropartículas Derivadas de Células , Exossomos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade
6.
Neurosci Lett ; 487(3): 394-9, 2011 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-21050879

RESUMO

Although flunarizine (FLN) has been widely used for migraine prophylaxis with clear success, the mechanisms of its actions in migraine prophylaxis are not completely understood. It has been hypothesized that migraine is a channelopathy, and abnormal activities of voltage-gated Na(+) and Ca(2+) channels might represent a potential mechanism of cortical hyperexcitability predisposing to migraine. The aim of the present study was to investigate the effects of FLN on Na(+) and Ca(2+) channels of cultured rat cortical neurons. Sodium currents (I(Na)) and calcium currents (I(Ca)) in cultured rat cortical neurons were monitored using whole-cell patch-clamp recordings. Both I(Na) and I(Ca) were blocked by FLN in a concentration-dependent manner with IC(50) values of 0.94µM and 1.77µM, respectively. The blockade of I(Na) was more powerful at more depolarizing holding potentials. The steady-state inactivation curve of I(Na) was shifted towards more hyperpolarizing potentials by FLN. FLN significantly delayed the recovery from fast inactivation of I(Na). Furthermore, the action of FLN in blocking I(Na) was enhanced at higher rates of channel activation. Blockades of these currents might help explain the mechanism underlying the preventive effect of FLN on migraine attacks.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Córtex Cerebral/efeitos dos fármacos , Flunarizina/farmacologia , Transtornos de Enxaqueca/fisiopatologia , Neurônios/efeitos dos fármacos , Animais , Células Cultivadas , Córtex Cerebral/metabolismo , Ativação do Canal Iônico/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Transtornos de Enxaqueca/metabolismo , Transtornos de Enxaqueca/prevenção & controle , Neurônios/metabolismo , Técnicas de Patch-Clamp , Canais de Potássio de Abertura Dependente da Tensão da Membrana/efeitos dos fármacos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Ratos , Canais de Sódio/efeitos dos fármacos , Canais de Sódio/metabolismo
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