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1.
CNS Neurosci Ther ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503421

RESUMO

Alzheimer's disease (AD) is characterized by ß-amyloid (Aß) deposition and Tau phosphorylation, in which its pathogenesis has not been cleared so far. The metabolism of Aß and Tau is critically affected by the autophagy. Abnormal autophagy is thought to be involved in the pathogenesis of AD, regulating autophagy may become a new strategy for AD treatment. In the early stage of AD, the presence of Aß and Tau can induce autophagy to promote their clearance by means of mTOR-dependent and independent manners. As AD progress, the autophagy goes aberrant. As a result, Aß and Tau generate continually, which aggravates both autophagy dysfunction and AD. Besides, several related genes and proteins of AD can also adapt autophagy to make an effect on the AD development. There seems to be a bi-directional relationship between AD pathology and autophagy. At present, this article reviews this relationship from these aspects: (a) the signaling pathways of regulating autophagy; (b) the relationships between the autophagy and the processing of Aß; (c) Aß and Tau cause autophagy dysfunction; (d) normal autophagy promotes the clearance of Aß and Tau; (e) the relationships between the autophagy and both genes and proteins related to AD: TFEB, miRNAs, Beclin-1, Presenilin, and Nrf2; and (f) the small molecules regulating autophagy on AD therapy. All of the above may help to further elucidate the pathogenesis of AD and provide a theoretical basis for clinical treatment of AD.

2.
Curr Med Chem ; 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31419926

RESUMO

BACKGROUND: Thromboangiitis obliterans (TAO) is a nonatherosclerotic thrombotic-occlusive vasculitis that affects the vessels of the small and medium sized extremities. No explicit etiology or pathogenesis of TAO has been proven, and more effective treatments are needed.

Objective: To summarize and present an overview of recent advances regarding the risk factors, mechanisms and treatments of TAO and to organize the related information into figures to provide a comparatively complete reference.

Methods: We searched PubMed for English-language literature about TAO without article type limits, including articles about the risk factors, pathological mechanisms and treatments of TAO in the last 10 years with essential supplements (references over ranges and English abstracts of Russian literature).

Results: After screening content of literatures, 99 references were evaluated. We found that risk factors of TAO include smoking, gene factors and periodontal diseases. The underlying mechanism of TAO involves in oxidative stress, immunity, hemodynamic changes, inflammation and so on. Moreover, similarities in genetic factors and cigarette relevance existed between periodontal diseases and TAO, so further relationship study of them are required. For TAO treatment, medicine, endovascular intervention and revascularization surgery, autologous cell therapy and novel therapies were also mentioned. Besides, a hypothesis that infection triggers autoimmunity in TAO could be speculated, in which TLR4 plays a key role.

Conclusions: 1. Puts forward a hypothesis that infections can trigger autoimmunity in TAO development, in which TLR4, as a key role, can activate immune signaling pathways and induce autoimmune cytokines expression. 2. Suggests a reconsideration about the association between periodontal diseases and TAO, such as they just share the same high-risk population. Controlling periodontal disease severity in TAO studies may provide new clues. 3. For TAO treatment, endovascular intervention and autologous cell therapy both showed promising long-term therapeutic effectiveness, in which autologous cell therapy is becoming more popular, although more clinical comparisons needed.

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3.
World J Clin Cases ; 7(6): 691-704, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30968034

RESUMO

As an irreversible and perennial process, aging is accompanied by functional and morphological declines in organs. Generally, aging liver exhibits a decline in volume and hepatic blood flow. Even with a preeminent regenerative capacity to restore its functions after liver cell loss, its biosynthesis and metabolism abilities decline, and these are difficult to restore to previous standards. Apoptosis is a programmed death process via intrinsic and extrinsic pathways, in which Bcl-2 family proteins and apoptosis-related genes, such as p21 and p53, are involved. Apoptosis inflicts both favorable and adverse influences on liver aging. Apoptosis eliminates transformed abnormal cells but promotes age-related liver diseases, such as nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, and liver cancer. We summarize the roles of apoptosis in liver aging and age-related liver diseases.

4.
Inflamm Res ; 68(6): 429-441, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30937466

RESUMO

BACKGROUND: Atherosclerosis (AS) is the main pathogeny of coronary heart disease, cerebral infarction and peripheral vascular disease. Endothelial dysfunction is one of the important pathogenesis of AS. As an important endothelium-derived relaxation factor, nitric oxide (NO) plays a role in cardiovascular protection and anti-AS function; but in the pathological state, endothelial nitric oxide synthase (eNOS) disorder causes an abnormal production of NO, which may damage endothelial function and trigger AS. This review summarized the research progresses in the treatment strategies for AS based on correcting the disordered eNOS/ NO signaling pathway. MAIN BODY: According to the topic, select the search terms 'atherosclerosis,' 'nitric oxide,' 'eNOS,' 'treatment,' 'management,' 'medication,' 'maintenance,' 'remission'. Using these terms, a structured literature search via multiple electronic databases was performed for the most recent trial evidence in recent years. We read and analyze these literatures carefully, classified these literatures according to their content, and then summarized and outlined the common main points in these classified literatures. Finally, literature data were organized to discuss these main points logically. We found that both aberrant expression and dysfunction of eNOS are closely related to AS development, and some new treatment strategies aimed at eNOS have been proposed, including upregulation of eNOS expression and inhibition of eNOS uncoupling. The former one is mainly related to inflammatory inhibition and protection of the PKB-eNOS signaling pathway; whereas the latter one is associated with the addition of the L-arginine substrate of eNOS, arginase inhibition, and the supplement of tetrahydrobiopterin, which can elevate no level. CONCLUSIONS: eNOS can be an important target for prevention and treatment of AS, and eNOS drugs may be another potent class of effective therapeutic treatment for AS following traditional lipid-lowering, anti-platelet, vasodilator drugs. But applying these experimental results to clinic treatment still requires further studies and development of biotechnology.


Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Animais , Humanos , Óxido Nítrico/metabolismo
5.
Clin Exp Rheumatol ; 37(5): 872-878, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943138

RESUMO

Rheumatoid arthritis is a chronic autoimmune disease characterised by unbearable joint pain as well as bone and cartilage destruction. Although RA development is greatly controlled, the pain and bone damage failed to be relieved and managed. Leukotriene B4 (LTB4) has been proved to play an essential role in the induction of pain and bone damage. The nerve injury of RA can promote the production of LTB4, which act on their receptors, leading to the increased release of pro-inflammatory cytokines and ROS to reduce neuron viability and pain threshold. Moreover, LTB4-BLT1 activation can also increase intracellular calcium concentration and neuron excitability as well as NF-κB pathway activation, which further promote the production of MMP-9 and CXC3R-1. The mutual promotion between LTB4 and neutrophil accumulation accelerates the release of TNF-α and IL-ß, which enhance both peripheral and central nerve system sensitisation. LTB4 also involve in TrpV1 channel activation and modulation of P2X3 receptor activation. All above mechanisms contribute to the development of RA pain. IL-23, cPLA2 and PI3K increase the production of CD11b+Gr1high myeloid subtype and calcium concentration, which promote the production of LTB4 and further accelerate IL-17 and TNF activation as well as calcium influx to conduce to osteoclastogenesis, resulting in aggregated bone damage. Our review is the first to conclude the signalling pathways and associated molecules in LTB4-induced pain and bone damage.


Assuntos
Artrite Reumatoide , Osso e Ossos/metabolismo , Leucotrieno B4 , Dor/metabolismo , Receptores do Leucotrieno B4/metabolismo , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/terapia , Humanos , Leucotrieno B4/metabolismo , Leucotrieno B4/fisiologia , Terapia de Alvo Molecular , Transdução de Sinais
6.
Neurosci Biobehav Rev ; 98: 177-184, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30648559

RESUMO

With aging, various factors deteriorate the normal sleep process that is essential for the restoration of functional and physical performance. Due to aging-related diseases, life changes, or aging itself, disturbances in normal sleep cycles can profoundly affect healthy aging. To understand the interconnections between aging and the factors influencing sleep, with emerging evidence accumulated in recent years, this study elaborates on the roles of aging in sleep from four perspectives: cortical thinning, white matter degeneration, neurotransmitter dysregulation, and circadian disorganization. In brief, with aging, cortical thinning can be induced by the deposition of neurotoxic substances, and white matter degeneration can be induced by vascular abnormalities. These alterations emerging in the brain jointly disrupt sleep spindles and slow waves, leading to sleep disturbances. Age-related dysregulation in neurotransmitters (including galanin, orexin, serotonin, and adenosine) directly impairs the sleep modulation system. Disorganization in the circadian system consisting of suprachiasmatic nucleus dysfunction, reduced light transmission, and local circadian clock disruption collectively interrupts circadian rhythms, also causing sleep disturbances in the older. Of note is the bidirectional relationship between aging and sleep, which required us to examine this issue from different perspectives.


Assuntos
Envelhecimento/fisiologia , Ritmo Circadiano/fisiologia , Sono/fisiologia , Núcleo Supraquiasmático/fisiologia , Animais , Encéfalo/fisiologia , Relógios Circadianos/fisiologia , Humanos
7.
Arch Med Res ; 49(4): 219-225, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-30269965

RESUMO

Hepatic injury is a major event in liver surgery and may lead to liver cell apoptosis. Nitric oxide (NO) is an unstable, carbon-centered radical with a short half-time and a key role in molecular signaling. Increasing evidence demonstrates that NO plays an important role in the liver cell apoptosis caused by hepatic ischemia reperfusion (IR) injury and other liver damage. Our recent article summarized the association between elevated nitric oxide levels and hepatic cell apoptosis during liver injury. This article reviews the newest research progress for the relationship between decreased nitric oxide levels and hepatic cell apoptosis inhibition during liver injury. It is shown that decreased NO level can influence liver apoptosis by promoting or inhibiting the signaling pathway involving the caspase family, BCL-2, mitochondria, oxidative stress, death receptors, and mitogen activated protein kinases, etc. This review outlines the literature basis for clinical application of anti-apoptosis treatment to relieve organ injury following liver surgery. NO-related drugs appear to be helpful in clinical treatment of liver diseases.


Assuntos
Apoptose/fisiologia , Hepatopatias/patologia , Fígado/lesões , Óxido Nítrico/metabolismo , Traumatismo por Reperfusão/patologia , Animais , Caspases/metabolismo , Humanos , Fígado/patologia , Masculino , Estresse Oxidativo , Transdução de Sinais
8.
Biomed Pharmacother ; 97: 423-428, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29091892

RESUMO

The pathological characteristics of atherosclerosis (AS) include lipid accumulation, fibrosis formation and atherosclerotic plaque produced in artery intima, which leads to vascular sclerosis, lumen stenosis and irritates the ischemic changes of corresponding organs. Endothelial dysfunction was closely associated with AS. Nitric oxide (NO) is a multifunctional signaling molecule involved in the maintenance of metabolic and cardiovascular homeostasis. NO is also a potent endogenous vasodilator and enters for the key processes that suppresses the formation vascular lesion even AS. NO bioavailability indicates the production and utilization of endothelial NO in organisms, its decrease is related to oxidative stress, lipid infiltration, the expressions of some inflammatory factors and the alteration of vascular tone, which plays an important role in endothelial dysfunction. The enhancement of arginase activity and the increase in asymmetric dimethylarginine and hyperhomocysteinemia levels all contribute to AS by intervening NO bioavailability in human beings. Diabetes mellitus, obesity, chronic kidney disease and smoking, etc., also participate in AS by influencing NO bioavailability and NO level. Here, we reviewed the relationship between NO bioavailability and AS according the newest literatures.


Assuntos
Aterosclerose/metabolismo , Endotélio Vascular/metabolismo , Óxido Nítrico/metabolismo , Animais , Arginina/análogos & derivados , Arginina/metabolismo , Aterosclerose/epidemiologia , Disponibilidade Biológica , Doenças Cardiovasculares/metabolismo , Humanos , Obesidade/epidemiologia , Obesidade/metabolismo , Estresse Oxidativo/fisiologia , Fumar/efeitos adversos , Fumar/epidemiologia , Fumar/metabolismo , Vasodilatação/fisiologia
9.
Oncotarget ; 8(60): 102640-102652, 2017 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-29254277

RESUMO

Various changes in the liver during aging can reduce hepatic function and promote liver injury. Aging is associated with high morbidity and a poor prognosis in patients with various liver diseases, including nonalcoholic fatty liver disease, hepatitis C and liver cancer, as well as with surgeries such as partial hepatectomy and liver transplantation. In addition, apoptosis increases with liver aging. Because apoptosis is involved in regeneration, fibrosis and cancer prevention during liver aging, and restoration of the appropriate level of apoptosis can alleviate the adverse effects of liver aging, it is important to understand the mechanisms underlying this process. Herein, we elaborate on the causes of apoptosis during liver aging, with a focus on oxidative stress, genomic instability, lipotoxicity, endoplasmic reticulum stress, dysregulation of nutrient sensing, and liver stem/progenitor cell activity.

10.
World J Gastroenterol ; 23(14): 2505-2510, 2017 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-28465634

RESUMO

Hepatic ischemia reperfusion injury (HIRI) is a clinical condition which may lead to cellular injury and organ dysfunction. The role of nitric oxide (NO) in HIRI is complicated and inconclusive. NO produced by endothelial nitric oxide synthase (eNOS) activation plays a protective role during early HIRI. But eNOS overexpression and the resulting excessive NO bioavailability can aggravate liver injury. NO induced by inducible nitric oxide synthase (iNOS) may have either a protective or a deleterious effect during the early phase of HIRI, but it may protect the liver during late HIRI. Here, we reviewed the latest findings on the role of NO during HIRI: (1) NO exerts a protective effect against HIRI by increasing NO bioavailability, downregulating p53 gene expression, decreasing inflammatory chemokines, reducing ROS via inhibiting the mitochondrial respiratory chain, activating sGC-GTP-cGMP signal pathway to reduce liver cell apoptosis, and regulating hepatic immune functions; (2) eNOS protects against HIRI by increasing NO levels, several eNOS/NO signal pathways (such as Akt-eNOS/NO, AMPK-eNOS/NO and HIF-1α-eNOS/NO) participating in the anti-HIRI process, and inhibiting over-expression of eNOS also protects against HIRI; and (3) the inhibition of iNOS prevents HIRI. Thus, the adverse effects of NO should be avoided, but its positive effect in the clinical treatment of diseases associated with HIRI should be recognized.


Assuntos
Hepatopatias/metabolismo , Fígado/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Apoptose , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Fígado/patologia , Hepatopatias/genética , Hepatopatias/patologia , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo III/genética , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Fatores de Tempo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
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