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BACKGROUND: The aim of this study was to shed light on the active ingredients and potential targets of Cassia Seed about anti-atherosclerosis based on network pharmacology. METHODS: The active ingredients and potential targets of Cassia Seed were obtained from traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and SwissTargetPrediction database. Then, atherosclerosis-related targets were screened via GeneCards, online mendelian inheritance in man, therapeutic target database and DrugBank database. The common targets and protein-protein interaction (PPI) network was later identified and built. Furthermore, we used the database for annotation, visualization and integrated discovery (DAVID) database server to accomplish the enrichment analysis. The compounds-targets-pathways network was ultimately constructed by Cytoscape. RESULTS: A total of 14 active ingredients and 475 related targets were sifted from Cassia Seed. Among 574 potential atherosclerotic targets, there were 99 targets overlapped with those of Cassia Seed. Topological analysis with Cytoscape revealed that proto-oncogene tyrosine-protein kinase proto-oncogene tyrosine-protein kinase Src, transcription factor AP-1 (JUN), mitogen-activated protein kinase 8 (MAPK8), mitogen-activated protein kinase 14 (MAPK14) and catenin beta-1 were considered as the hub gene. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis suggested that the Cassia Seed had the potential to influence varieties of biological processes and pathways, including positive regulation of smooth muscle cell proliferation, inflammatory response, tumor necrosis factor (TNF) signaling pathway, vascular endothelial growth factor (VEGF) signaling pathway and arachidonic acid (ARA) metabolism. CONCLUSION: Taken together, our findings support that anti-atherosclerosis effects of Cassia Seed are characterized by multi-component, multi-target and multi-path mechanism of action.
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Cassia , Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Proteínas Quinases Ativadas por Mitógeno , Farmacologia em Rede , Sementes , Tirosina , Fator A de Crescimento do Endotélio VascularRESUMO
Hepatic ischemia-reperfusion injury (HIRI) is a major clinical cause of morbidity and mortality in liver surgery and transplantation. Many studies have found that nitric oxide (NO) plays an important role in the HIRI and its increase or decrease can affect the progression and outcome of HIRI. However, the role of NO in HIRI is controversial and complicated. NO derived by endothelial NO synthase (eNOS) shows a protective role in HIRI, while excessive NO derived by inducible NO synthase (iNOS) accelerates inflammation and increases oxidative stress, further aggravating HIRI. Nevertheless, the overexpression of eNOS may exacerbate HIRI and iNOS-derived NO in some cases reduces HIRI. Here we review the new progress in the understanding of the roles of NO during HIRI: (1) NO possesses different roles in HIRI by increasing NO bioavailability, down-regulating leukotriene C4 synthase, inhibiting the activation of the nuclear factorκB (NFκB) pathway, enhancing cell autophagy, and reducing inflammatory cytokines and reactive oxygen species (ROS). And NO has both protective and deleterious effects by regulating apoptotic factors; (2) eNOS promotes NO production and suppresses its own overexpression, exerting a hepatoprotective effect reversely. Its activation is regulated by the PI3K/Akt and KLF2/AMPK pathways; and (3) iNOS derived NO mainly has deteriorating effects on HIRI, while it may have a protective function under some conditions. Their expression should reach a balance to reduce the adverse side and make NO protective in the treatment of HIRI. Thus, it can be inferred that NO modulating drugs may be a new direction in the treatment of HIRI or may be used as an adjunct to mitigate HIRI for the purpose of protecting the liver.
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Vascular dementia (VaD) is a neurodegenerative disease, with cognitive dysfunction attributable to cerebrovascular factors. At present, it is the second most frequently occurring type of dementia in older adults (after Alzheimer's disease). The underlying etiology of VaD has not been completely elucidated, which limits its management. Currently, there are no approved standard treatments for VaD. The drugs used in VaD are only suitable for symptomatic treatment and cannot prevent or reduce the occurrence and progression of VaD. This review summarizes the current status of pharmacological treatment for VaD, from the perspective of the molecular mechanisms specified in various pathogenic hypotheses, including oxidative stress, the central cholinergic system, neuroinflammation, neuronal apoptosis, and synaptic plasticity. As VaD is a chronic cerebrovascular disease with multifactorial etiology, combined therapy, targeting multiple pathophysiological factors, may be the future trend in VaD.
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Hepatic ischemia reperfusion injury (HIRI) is an important cause of liver dysfunction after liver transplantation for the patients suffered from fatty liver, non-alcoholic cirrhosis, or liver cancer. It is closely related to liver cells apoptosis. Therefore, how to maintain the stable state of cell apoptosis is important to protect the liver from HIRI. Drug treatment basically applies some active substances directly or indirectly, reducing HIRI. But their toxic side effects limit the clinical applications. Differently, non-drug treatment means making use of other kinds of measures to reduce the damage, such as non-pharmaceutical preparations, surgical methods, inhalation or perfusion gas, and so on. Non-drug treatments have been shown to balance cell apoptosis and reduce liver damage during HIRI. This review summarized the progresses in the roles of non-drug treatments on liver cells apoptosis during HIRI in recent years, focusing on apoptosis inducing factors, its signal transduction pathway, and downstream molecules, etc., expecting to elucidate non-drug treatments of anti-HIRI more systematically.
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Apoptose , Transplante de Fígado , Fígado/patologia , Traumatismo por Reperfusão/prevenção & controle , Humanos , Fígado/irrigação sanguínea , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodosRESUMO
Sleep disorders are common in patients with Alzheimer's disease, and can even occur in patients with amnestic mild cognitive impairment, which appears before Alzheimer's disease. Sleep disorders further impair cognitive function and accelerate the accumulation of amyloid-ß and tau in patients with Alzheimer's disease. At present, sleep disorders are considered as a risk factor for, and may be a predictor of, Alzheimer's disease development. Given that sleep disorders are encountered in other types of dementia and psychiatric conditions, sleep-related biomarkers to predict Alzheimer's disease need to have high specificity and sensitivity. Here, we summarize the major Alzheimer's disease-specific sleep changes, including abnormal non-rapid eye movement sleep, sleep fragmentation, and sleep-disordered breathing, and describe their ability to predict the onset of Alzheimer's disease at its earliest stages. Understanding the mechanisms underlying these sleep changes is also crucial if we are to clarify the role of sleep in Alzheimer's disease. This paper therefore explores some potential mechanisms that may contribute to sleep disorders, including dysregulation of the orexinergic, glutamatergic, and γ-aminobutyric acid systems and the circadian rhythm, together with amyloid-ß accumulation. This review could provide a theoretical basis for the development of drugs to treat Alzheimer's disease based on sleep disorders in future work.
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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.
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Doença de Alzheimer/fisiopatologia , Autofagia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Humanos , Proteínas tau/genética , Proteínas tau/metabolismoRESUMO
BACKGROUND: Thromboangiitis obliterans (TAO) is a nonatherosclerotic thromboticocclusive 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: The study aimed to summarize and present an overview of recent advances regarding the risk factors, mechanisms and treatments of TAO and to organize the related information in 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 works of literature, 99 references were evaluated. We found that risk factors of TAO include smoking, gene factors and periodontal diseases. The underlying mechanism of TAO involves 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 study of relationship was 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. CONCLUSION: 1. A hypothesis is put forward that infections can trigger autoimmunity in TAO development, in which TLR4, as a key agent, can activate immune signaling pathways and induce autoimmune cytokines expression. 2. It is suggested to reconsider the association between periodontal diseases and TAO, as they 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 are needed.
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Tromboangiite Obliterante , Autoimunidade , Humanos , Fatores de Risco , Fumar/efeitos adversos , Tromboangiite Obliterante/etiologia , Tromboangiite Obliterante/terapia , Resultado do TratamentoRESUMO
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.
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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.
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Envelhecimento/fisiologia , Ritmo Circadiano/fisiologia , Sono/fisiologia , Núcleo Supraquiasmático/fisiologia , Animais , Encéfalo/fisiologia , Relógios Circadianos/fisiologia , HumanosRESUMO
Alzheimer disease (AD) is characterized as a chronic neurodegenerative disease associated with aging. The clinical manifestations of AD include latent episodes of memory and cognitive impairment, psychiatric symptoms and behavioral disorders, as well as limited activities in daily life. In developed countries, AD is now acknowledged as the third leading cause of death, following cardiovascular disease and cancer. The pathogenesis and mechanism of AD remain unclear, although some theories have been proposed to explain AD, such as the theory of ß-amyloid, the theory of the abnormal metabolism of tau protein, the theory of free radical damage, the theory of the inflammatory response, the theory of cholinergic damage, etc. Effective methods to predict, prevent or reverse AD are unavailable, and thus the development of new, efficient therapeutic drugs has become a current research hot spot worldwide. The isolation and extraction of active components from natural drugs have great potential in treating AD. These drugs possess the advantages of multiple targets in multiple pathways, fewer side effects and a long duration of curative effects. This article summaries the latest research progress regarding the mechanisms of natural drugs in the treatment of AD, providing a review of the literature and a theoretical basis for improving the clinical treatment of AD.
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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.
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Apoptose/fisiologia , Hepatopatias/patologia , Fígado/lesões , Óxido Nítrico/metabolismo , Traumatismo por Reperfusão/patologia , Animais , Caspases/metabolismo , Humanos , Fígado/patologia , Masculino , Estresse Oxidativo , Transdução de SinaisRESUMO
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.
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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/fisiologiaRESUMO
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.
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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/metabolismoRESUMO
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.
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The aim of the present study was to explore the mechanism underlying the effects of a selective liver nitric oxide (NO) donor, O2-vinyl1-(pyrrolidin-1-yl)-diazen-1-ium-1,2-diolate (V-PYRRO/NO), on the gene expression of leukotriene C4 synthase (LTC4S) during hepatic ischemia/reperfusion (I/R). Adult male Sprague-Dawley rats were divided into 3 groups: Sham (control), I/R and V-PYRRO/NO + I/R groups. The liver was subjected to 1 h of partial hepatic ischemia followed by 5 h of reperfusion, saline or V-PYRRO/NO (1.06 µmol/kg/h) administered intravenously. The mRNA expression levels of LTC4S in rat liver tissue were examined by the reverse transcription-polymerase chain reaction method, the protein expression levels of nuclear factor-κB (NF-κB) p65, p50 and IκBα in liver cell lysates and nuclear extracts were detected by western blot analysis. Hepatic mRNA expression of LTC4S was lower in V-PYRRO/NO + I/R group compared to the I/R group. In addition, the protein expression levels of NF-κB p65 and p50 in the nucleus extract were lower in the V-PYRRO/NO + I/R group when compared with the I/R group. However, the IκBα protein in the 3 groups was not changed. Immunohistochemistry staining revealed that the I/R liver exhibited strong cytoplasmic and nuclear staining for NF-κB p65; however, the V-PYRRO/NO + I/R group liver presented slight cytoplasmic and nuclear staining. In conclusion, V-PYRRO/NO may downregulate LTC4S mRNA expression by inhibiting NF-κB activation independent of IκBα during hepatic I/R injury.
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The purpose of this article was to help one preschool leukemia child to face the stress of hospitalization by using play. The child, facing stress of hospitalization, used coping behaviors that included regression and escapism. The cognitive theories for entertainment, role-play and talking-story play were adopted to release the child's stress and anxiety. Clinical workers may like to use the findings of this article to promoter children's maturation and ability to cope with stress during hospitalization.