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1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(4): 666-671, 2023 Aug.
Artigo em Zh | MEDLINE | ID: mdl-37654147

RESUMO

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.


Assuntos
Hiperuricemia , Óxido Nítrico , Humanos , Ácido Úrico , Disponibilidade Biológica , Citocinas
2.
Int J Nanomedicine ; 16: 1423-1434, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33654394

RESUMO

BACKGROUND: Interleukin-1ß (IL-1)-treated mesenchymal stem cells (MSCs) and IL-1-MSCs-conditioned medium (CM) exert anti-inflammatory roles. Astrocytes are essential for the modulation of synaptic activity and neuronal homeostasis in the brain. Exosomes are the critical mediators in intercellular communication. However, the mechanism underlying the anti-inflammatory effect of IL-1-treated MSCs remains unknown. METHODS: In this study, exosomes (IL-1-Exo) were isolated from IL-1-treated MSCs. In addition, lipopolysaccharide (LPS)-treated hippocampal astrocytes and status epilepticus (SE) mice were treated with IL-1-Exo. Inflammatory activity, astrogliosis, and cognitive performance were measured to determine the effect of IL-1-Exo on inflammation. RESULTS: The results revealed that IL-1-Exo significantly inhibited LPS-induced astrogliosis and inflammatory responses of astrocytes. Also, IL-1-Exo reversed the LPS-induced effect on calcium signaling. The Nrf2 signaling pathway was associated with the effect of IL-1-Exo in LPS-treated astrocytes. Furthermore, IL-1-Exo reduced the inflammatory response and improved the cognitive performance of SE mice. CONCLUSION: The results suggest that IL-1-Exo inhibited LPS-induced inflammatory responses in astrocytes and SE mice and that the effect of IL-1-Exo was primarily mediated through the Nrf-2 signaling pathway. This study provides a new understanding of the molecular mechanism of inflammation-associated brain diseases and an avenue to develop nanotherapeutic agents for the treatment of inflammatory conditions in the brain.


Assuntos
Astrócitos/patologia , Exossomos/metabolismo , Hipocampo/patologia , Inflamação/terapia , Interleucina-1beta/farmacologia , Células-Tronco Mesenquimais/citologia , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Animais , Animais Recém-Nascidos , Anti-Inflamatórios/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Comportamento Animal/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Exossomos/efeitos dos fármacos , Exossomos/ultraestrutura , Humanos , Inflamação/patologia , Lipopolissacarídeos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Transdução de Sinais/efeitos dos fármacos , Estado Epiléptico/patologia
3.
Zhen Ci Yan Jiu ; 45(12): 954-60, 2020 Dec 25.
Artigo em Zh | MEDLINE | ID: mdl-33415852

RESUMO

OBJECTIVE: To observe the effect of crossing nape electroacupuncture(EA) on cough count (CCnt), cough incubation period and blood routine, liver function, renal function, myocardial enzymology, and heart, liver and kidney pathological structure in guinea pig with cough reflex disorder after cerebral hemorrhage, so as to evaluate the efficacy and safety of crossing nape EA in the treatment of cough reflex disorder after cerebral hemorrhage. METHODS: A total of 160 male pure white guinea pigs were randomly divided into normal group, model group, acupuncture group, crossing nape EA group and nape EA group (n=32 in each group). These 5 groups were further divided into 1, 3, 7 and 14 d subgroups(n=8 in each subgroup). The model of cough reflex disorder after cerebral hemorrhage was established by injection of the guinea pigs' autoblood (50 µL) into the basal ganglia region confirmed by Longa's neurologic examination grading system(0-4 points). Acupuncture was applied to bilateral "Fengchi" (GB20) and "Yifeng" (SJ17) in the acupuncture group. In the crossing nape EA group, the positive pole of the needle is connected to SJ17, while the negative pole is connected to the opposite side of GB20(2 Hz, 0.5 mA). In the nape EA group, the positive pole of the needle is connected to SJ17, while the negative pole is connected to the same side of GB20(2 Hz, 0.5 mA). All treatments were applied 20 min each time, once a day. The changes of CCnt and cough incubation period were recorded by Buxco device. The changes of blood routine, liver function, kidney function, myocardial enzyme and other laboratory indexes were monitored by automatic analyzer instrument. The pathological changes of heart, liver and kidney of guinea pigs were observed by transmission electron microscopy. RESULTS: Compared with the normal group, the guinea pigs' neurological deficit scores in the model group were significantly increased at each time point (P<0.01). Compared with the model group, the neurological deficit scores of the acupuncture group, crossing nape EA group and nape EA group at 3 d, 7 d and 14 d all decreased (P<0.01, P<0.05). Following modeling, the CCnt at each time point in the model group was significantly reduced (P<0.01), and the cough latency was significantly prolonged (P<0.01). After interventions, the CCnts were increased and the incubation periods of cough were shortened (P<0.05, P<0.01) at 7 d and 14 d in the 3 intervention groups, and were superior in the crossing nape EA group than those of acupuncture group and nape EA group (P<0.05, P<0.01). The improvement degrees of these 2 indexes in the nape EA group at 14 d were better than those of the acupuncture group (P<0.05). There were no significant differences among the 3 groups in red blood cells counting, hemoglobin, myocardial enzymes, liver and kidney function (P>0.05). Compared with the normal group, the WBC counts in all the time points (except 1 d after operation) were significantly increased(P<0.01) in the model group. In comparison with the model group, the WBC counts at 3 d in crossing nape EA group, and at 7 d and 14 d in the 3 intervention groups decreased (P<0.01, P<0.05). Meanwhile, the WBC counts were lower in the crossing nape EA group at 7 d and 14 d than those of acupuncture group and nape EA group (P<0.05). The results of transmission electron microscopy showed that the histopathological structure of heart, liver and kidney of guinea pigs in each group had no significant changes. CONCLUSION: Crossing nape EA is safe and effective in the treatment of cough reflex disorder after cerebral hemorrhage in guinea pigs. In addition, guinea pigs will have an inflammatory response after cerebral hemorrhage, and crossing nape EA may have a certain anti-inflammatory effect.


Assuntos
Eletroacupuntura , Pontos de Acupuntura , Animais , Hemorragia Cerebral/terapia , Tosse/etiologia , Tosse/terapia , Cobaias , Masculino , Ratos , Ratos Sprague-Dawley , Reflexo
4.
Artigo em Inglês | MEDLINE | ID: mdl-33335556

RESUMO

The regulatory effect of luteolin on the progression of Alzheimer's disease (AD) remains unclear from the perspective of apoptosis. The present study aimed to investigate the protective effects of luteolin against Aß 25-35-induced cell apoptosis in pheochromocytoma (PC-12) cells. Aß 25-35 was used to induce an in vitro model of AD. Estradiol was used as a positive control. The PC-12 cells were incubated with luteolin alone or in combination with fulvestrant or U0126. The results showed that luteolin treatment significantly prevents Aß 25-35-induced decrease in cell viability and inhibits Aß 25-35-induced cell apoptosis. After the addition of fulvestrant and U0126, the apoptosis rate of PC-12 cells increased significantly. In addition, luteolin treatment significantly upregulated the expression of Bcl-2 and downregulated the expression of Bax and caspase-3, whereas fulvestrant and U0126 partially reversed the effects of luteolin. Moreover, luteolin treatment upregulated the expression of ERß and p-ERK1/2, whereas fulvestrant blocked the expression of p-ERK1/2. The study showed that luteolin could activate the ER/ERK/MAPK signalling pathway to protect PC-12 cells against Aß 25-35-induced cell apoptosis via selectively acting on ERß. Thus, luteolin may be considered as a potential novel therapeutic strategy for AD.

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