As the number of individuals with non-alcoholic fatty liver disease (NAFLD) has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged.
Arrhythmias, Cardiac ; Atherosclerosis ; Brain ; Cerebrovascular Disorders ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Dyslipidemias ; Fatty Liver ; Heart ; Humans ; Hypertension ; Inflammation ; Insulin Resistance ; Kidney Diseases ; Liver ; Mass Screening ; Metabolic Diseases ; Metabolism ; Non-alcoholic Fatty Liver Disease* ; Obesity ; Oxidative Stress ; Renal Insufficiency ; Renal Insufficiency, Chronic ; Risk Assessment ; Stroke

INTRODUCTIONThe present study aimed to investigate the possible associations between serum levels of visfatin, an adipokine, and atherosclerosis in patients with ischaemic cerebrovascular disease.

METHODSA total of 95 participants were recruited for this study. Group A comprised 35 individuals with no history of cerebrovascular disease (control group) and Group B comprised 60 patients with ischaemic cerebrovascular disease. Group B was further categorised into two subgroups based on the ultrasonographic findings of the common carotid artery intima‑media thickness (CCA‑IMT) - Group B1 consisted of 21 patients with no atherosclerosis (i.e. CCA‑IMT ≤ 0.9 mm) and Group B2 consisted of 39 patients with atherosclerosis (i.e. CCA‑IMT > 0.9 mm). The body mass index, fasting blood total cholesterol, triglycerides, high‑density lipoprotein cholesterol, low‑density lipoprotein cholesterol and glucose levels of each patient were measured. Serum visfatin levels were determined using enzyme‑linked immunosorbent assays. Visfatin levels were compared between groups, and stepwise logistic regression analysis was used to identify risk factors for atherosclerosis, including visfatin levels.

RESULTSThe mean serum visfatin level of the patients in Group B was higher than that in Group A (75.5 ± 77.80 ng/mL vs. 8.6 ± 4.69 ng/mL; p < 0.05) and the level was higher in patients from Group B2 than those from Group B1 (89.0 ± 80.68 ng/mL vs. 50.4 ± 72.44 ng/mL; p < 0.05). Multivariate regression analysis showed that CCA‑IMT values were not significantly associated with visfatin levels. However, logistic regression analysis showed that serum visfatin was an independent risk factor for atherosclerosis (odds ratio 37.80; p = 0.004).

CONCLUSIONSerum visfatin may be an independent risk factor for cerebral infarction, as high serum visfatin levels are positively associated with the underlying pathogenic mechanisms of ischaemic cerebrovascular disease.

Adipokines ; metabolism ; Adipose Tissue ; pathology ; Adult ; Aged ; Atherosclerosis ; blood ; complications ; Body Mass Index ; Brain Ischemia ; blood ; complications ; Carotid Intima-Media Thickness ; Case-Control Studies ; Cerebrovascular Disorders ; blood ; complications ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Inflammation ; Logistic Models ; Male ; Middle Aged ; Nicotinamide Phosphoribosyltransferase ; blood ; Risk Factors

AIM: To illuminate the molecular targets for schisandrin against cerebrovascular disease based on the combined methods of network pharmacology prediction and experimental verification. METHOD: A protein database was established through constructing the drug-protein network from literature mining data. The protein-protein network was built through an in-depth exploration of the relationships between the proteins. The computational platform was implemented to predict and extract the sensitive sub-network with significant P-values from the protein-protein network. Then the key targets and pathways were identified from the sensitive sub-network. The most related targets and pathways were also confirmed in hydrogen peroxide (H2O2)-induced PC12 cells by Western blotting. RESULTS: Twelve differentially expressed proteins (gene names: NFKB1, RELA, TNFSF10, MAPK1, CHUK, CASP8, PIGS2, MAPK14, CREB1, IFNG, APP, and BCL2) were confirmed as the central nodes of the interaction network (45 nodes, 93 edges). The NF-κB signaling pathway was suggested as the most related pathway of schisandrin for cerebrovascular disease. Furthermore, schisandrin was found to suppress the expression and phosphorylation of IKKα, as well as p50 and p65 induced by H2O2 in PC12 cells by Western blotting. CONCLUSION The computational platform that integrates literature mining data, protein-protein interactions, sensitive sub-network, and pathway results in identification of the NF-κB signaling pathway as the key targets and pathways for schisandrin.
Animals ; Cerebrovascular Disorders ; drug therapy ; genetics ; metabolism ; Cyclooctanes ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Gene Regulatory Networks ; drug effects ; Humans ; Lignans ; pharmacology ; Molecular Targeted Therapy ; PC12 Cells ; Polycyclic Compounds ; pharmacology ; Protein Interaction Maps ; drug effects ; Rats ; Signal Transduction ; drug effects

Animals ; Cardiovascular Diseases ; etiology ; Cerebrovascular Disorders ; etiology ; Homocysteine ; metabolism ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Genetic

PURPOSE: Clopidogrel is a prodrug that requires transformation into an active metabolite by cytochrome P450 (CYP) in the liver in order to irreversibly inhibit the P2Y12 adenosine diphosphate platelet receptor. CYP2C19 polymorphism has been reported to correlate with reduced antiplatelet activity of clopidogrel in coronary artery disease. We assessed the association between CYP2C19 polymorphism and clopidogrel resistance in patients with cerebrovascular disease. MATERIALS AND METHODS: We retrospectively gathered data from patients who experienced cerebrovascular disease, received clopidogrel, and were tested for clopidogrel resistance and CYP2C19 polymorphism. Clopidogrel resistance was tested by the VerifyNow P2Y12 system, and the CYP2C19 polymorphism was tested by the Seeplex CYP2C19 ACE Genotyping system. Clopidogrel resistance was expressed in P2Y12 reaction units (PRU) and percent inhibition. High PRU and low percent inhibition suggests clopidogrel resistance. CYP2C19 polymorphisms were expressed as extensive, intermediate, and poor metabolizers. Clopidogrel resistance was assessed according to the subgroup of CYP2C19 polymorphism. RESULTS: A total of 166 patients were evaluated. The PRU values of extensive CYP2C19 metabolizers (195.0+/-84.9) were significantly lower than those of intermediate and poor metabolizers (237.9+/-88.0, 302.2+/-58.9). The percent inhibition of extensive metabolizers (44.6+/-21.8) was significantly higher than that of intermediate and poor metabolizers (30.5+/-21.5, 14.0+/-13.4). CONCLUSION: Intermediate and poor metabolizing CYP2C19 polymorphism is associated with reduced clopidogrel antiplatelet activity in patients with cerebrovascular disease. The clinical implications of this finding require further investigation.
Aged ; Aryl Hydrocarbon Hydroxylases/*genetics/metabolism ; Cerebrovascular Disorders/*drug therapy/*enzymology/genetics ; Drug Resistance/genetics ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors/pharmacokinetics/*therapeutic use ; Polymorphism, Single Nucleotide ; Retrospective Studies ; Ticlopidine/*analogs & derivatives/pharmacokinetics/therapeutic use

OBJECTIVETo observe the intervention and mechanism of Weinaokang capsule (WNK) on cognitive impairment rats induced by chronic cerebral hypoperfusion.

METHODThe bilateral common carotid arteries of rats were ligated. Rats were intragastrically administrated with WNK 4 weeks after the ligation. After 8 weeks of administration, persistent time of rats on finding the platform in MORRIS water maze was measured, meanwhile, content of acetylcholine (ACh) in brain tissue was measured by HPLC-ECD, activity of acetylcholine esterase (AChE) and superoxide dismutase (SOD), content of malonaldehyde (MDA) was measured by colorimetric method.

RESULTAfter 4-8 weeks of administration, the time of finding the platform in WNK group was significantly shorter than in the model group, activity of AChE in brain tissue was significantly reduced (P < 0. 05), content of ACh was significantly increased (P < 0.05-0.01), activity of SOD was significantly reinforced (P < 0.05).

CONCLUSIONWNK capsule can improve the cognitive impairment induced by chronic cerebral hypoperfusion, and its mechanism may be associated with reinforcing the capability of scavenging free radical and protecting the cholinergic system.

Acetylcholine ; metabolism ; Acetylcholinesterase ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Cerebrovascular Disorders ; drug therapy ; metabolism ; Chronic Disease ; Drugs, Chinese Herbal ; pharmacology ; Male ; Malondialdehyde ; metabolism ; Maze Learning ; drug effects ; Memory ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

OBJECTIVETo investigate the expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) in monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood flow occlusion.

METHODSThe monkeys were immediately removed brain after death in operation of group A (identical temperature perfusion group) and group B (ultraprofound hypothermia perfusion group). Immunohistochemical technique was used to determine frontal cellular expression of NGF and GDNF. Statistics were analyzed by ANOVA analyses with significance level at P < 0.05.

RESULTSThe expressions of NGF and GDNF in the group B were significantly higher than those in the group A (P < 0.05).

CONCLUSIONNGF and GDNF increased significantly in the monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood flow occlusion. It may be a protective mechanism for neuron survival and neural function recovery.

Animals ; Brain ; metabolism ; Cell Survival ; physiology ; Cerebrovascular Circulation ; physiology ; Cerebrovascular Disorders ; metabolism ; physiopathology ; Cytoprotection ; physiology ; Glial Cell Line-Derived Neurotrophic Factor ; metabolism ; Hypothermia, Induced ; Hypoxia-Ischemia, Brain ; metabolism ; physiopathology ; prevention & control ; Macaca mulatta ; Nerve Growth Factor ; metabolism ; Neurons ; metabolism ; Recovery of Function ; physiology ; Reperfusion Injury ; metabolism ; physiopathology ; prevention & control ; Resuscitation ; Up-Regulation ; physiology

INTRODUCTIONCardiovascular disease is the leading cause of death and morbidity among postmenopausal women, and oestrogen deficiency may be an important factor in its development. The role of oestrogen replacement in preventing cardiovascular disease is controversial. The aim of this descriptive review is to analyse the available data and to recommend evidence-based practice guidelines pertaining to hormone therapy in the context of cardiovascular and cerebrovascular health.

MATERIALS AND METHODSRelevant clinical trials were identified by computerised literature search. The collated data were presented to fellow gynaecologists for review, analysis of results and discussion in a series of meetings dedicated to finding the best evidence in menopause management. The evidence was used to formulate clinical practice guidelines for the management of women with significant cardiovascular risk factors.

RESULTSEvidence from animal studies and observational trials supported a cardio-protective effect of postmenopausal hormone therapy. More recent randomised clinical trial data have shown no significant reduction of coronary heart disease, and have confirmed a higher incidence of stroke and venous thromboembolism.

CONCLUSIONSThe evidence is widely divergent regarding postmenopausal hormone therapy and cardiovascular risk. More consistent data are available reporting an increased risk in the incidence of venous thromboembolism and stroke. It is important to be clear about the indications of hormone use and to utilise alternative modalities to promote cardiovascular health in the postmenopausal population.

Aged ; Cardiovascular Diseases ; prevention & control ; Cerebrovascular Disorders ; prevention & control ; Estrogens ; deficiency ; metabolism ; Female ; Hormone Replacement Therapy ; Humans ; Menopause ; Middle Aged ; Practice Guidelines as Topic

Migraine often runs in families and is associated with both genetic and environmental factors. Clinical and genetic heterogeneity as well as the influence of environmental factors have hampered the identification of the gene responsible for migraine disorder. Family/twin studies suggest the presence of hereditary susceptibility. Several different types of mutations or association studies with genetic polymorphism in neurotransmitters, inflammatory cytokines, homocysteine metabolism, mitochondria, or other risk genes in cerebrovascular disorders have been reported. Recently, progress of molecular genetics in familial hemiplegic migraine has provided important insights, a channelopathy, and now extending to a growing list of membrane excitability disorders. Further identification of candidate genes for migraine and exploring the correlation between phenotype and genotype are expected in the future for the understanding of migraine pathophysiology.
Cerebrovascular Disorders ; Channelopathies ; Cytokines ; Genetic Heterogeneity ; Genetics* ; Genotype ; Homocysteine ; Humans ; Membranes ; Metabolism ; Migraine Disorders* ; Migraine with Aura ; Mitochondria ; Molecular Biology ; Neurotransmitter Agents ; Phenotype ; Polymorphism, Genetic

S100beta is one kind of the calcium binding proteins. As growth factor of neuraxon, it is excreted by neuroglial cell, and distributing in nerve tissue extensively. Although S100beta has very important values neurophysiological, it also has neurotoxicity with excreting overmuch. Concentration of S100beta changes regularity in serum after the brain injury. In addition, it has a close relations with the degree of brain damage, which can be regarded as the neural new marker of biochemistry after brain damage. The advances of S100beta protein, in the research on neurophysiological values and its application for nerve tissue injury, disease were reviewed.
Alzheimer Disease/pathology* ; Biomarkers/blood* ; Brain Injuries/physiopathology* ; Cerebrovascular Disorders/pathology* ; Humans ; Nerve Growth Factors/blood* ; Neuroglia/metabolism* ; Postmortem Changes ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins/blood* ; Severity of Illness Index ; Time Factors