Ischemic Cardio-cerebrovascular Diseases Research Articles

Advances in the Anti-Atherosclerotic Mechanisms of Epigallocatechin Gallate.

Atherosclerosis (AS) is a common clinical sickness and the major pathological basis of ischemic cardiocerebrovascular diseases (CCVDs). The pathogenesis of AS involves a variety of risk factors, and there is a lack of effective preventive and curative drugs that can completely treat AS. In recent years, with the improvement of people's living standards and changes in dietary habits, the morbidity and mortality rates of AS are on the rise, and the age of onset tends to be younger. The formation of AS is closely related to a variety of factors, and the main factors include lipid metabolism disorders, endothelial damage, inflammation, unstable plaques, etc. Epigallocatechin gallate (EGCG), as one of the main components of catechins, has a variety of pharmacological effects, and its role in the prevention of AS and the protection of cardiovascular and cerebral blood vessels has been highly valued. Recent epidemiological investigations and various in vivo and ex vivo experiments have shown that EGCG is capable of resisting atherosclerosis and reducing the morbidity and mortality of AS. In this paper, we reviewed the anti-AS effects of EGCG and its mechanisms in recent years, including the regulation of lipid metabolism, regulation of intestinal flora disorders, improvement of vascular endothelial cell functions, inhibition of inflammatory factors expression, regulation of inflammatory signaling pathways, inhibition of matrix metalloproteinase (MMP) expression, and inhibition of platelet aggregation, which are helpful for the prevention of cardiocerebrovascular diseases.

Ischemic cardio-cerebrovascular disease and all-cause mortality in Chinese elderly patients: a propensity-score matching study

BackgroundIschemic cardio-cerebrovascular disease is the leading cause of mortality worldwide. However, studies focusing on elderly and very elderly patients are scarce. Hence, our study aimed to characterize and investigate the long-term prognostic implications of ischemic cardio-cerebrovascular diseases in elderly Chinese patients.MethodsThis retrospective cohort study included 1026 patients aged ≥ 65 years who were categorized into the mono ischemic cardio-cerebrovascular disease (MICCD) (either coronary artery disease or ischemic stroke/transient ischemic attack) (n = 912) and the comorbidity of ischemic cardio-cerebrovascular disease (CICCD) (diagnosed with both coronary artery disease and ischemic stroke/transient ischemic attack at admission) (n = 114). The primary outcome was all-cause death. The mortality risk was evaluated using the Cox proportional hazards risk model with multiple adjustments by conventional and propensity-score-based approaches.ResultsOf the 2494 consecutive elderly patients admitted to the hospital, 1026 (median age 83 years [interquartile range]: 76.5–86.4; 94.4% men) met the inclusion criteria. Patients with CICCD consisted mostly of very elderly (79.2% vs. 66.1%, P < 0.001) individuals with a higher burden of comorbidities. Over a median follow-up of 10.4 years, 398 (38.8%) all-cause deaths were identified. Compared with the MICCD group, the CICCD group exhibited a higher adjusted hazard ratio (HR) (95% confidential interval, CI) of 1.71 (1.32–2.39) for long-term mortality after adjusting for potential confounders. The sensitivity analysis results remained robust. After inverse probability of treatment weighting (IPTW) modeling, the CICCD group displayed an even worse mortality risk (IPTW-adjusted HR: 2.07; 95% CI 1.47–2.90). In addition, anemia (adjusted HR: 1.48; 95% CI 1.16–1.89) and malnutrition (adjusted HR: 1.43; 95% CI 1.15–1.78) are also independent risk factors for all-cause mortality among elderly and very elderly patients.ConclusionsOur results thus suggest that elderly patients with ischemic cardio-cerebrovascular disease and anemia or malnutrition may have higher mortality, which may be predicted upon admission. These findings, however, warrant further investigation.Graphical

Double closed-loop feedback control strategy for enhanced external counterpulsation to regulate hemodynamic response of human common carotid artery

Enhanced external counterpulsation (EECP) is a mechanical therapy for the clinical management of ischemic cardio-cerebrovascular diseases. Applying different EECP modes to different patients would be based on the experience of physicians. Existing hemodynamic models could describe the quantitative relationship between different EECP modes and hemodynamic parameters of specific parts of human blood circulatory system. However, currently there is no closed-loop control system available for precisely, personally, and intelligently performing the EECP. Therefore, to significantly improve the clinical benefits of rehabilitation treatment of ischemic cardio-cerebrovascular diseases with the EECP, this study developed a double closed-loop physiological control algorithm for the EECP device. Firstly, a detailed lumped parameter model describing the hemodynamics of human blood circulatory system was updated based on the available models; then the EECP device was coupled to it and the updated model was tested with the clinical data; finally, a double closed-loop feedback control strategy for precise regulation of the carotid hemodynamic response by the EECP was proposed. The control objectives were to maintain the mean arterial pressure and EECP pressure amplitude of patients with two gain-scheduled proportional-integral (PI) controllers. In-silico results showed that the clinical data can prove the accuracy of the updated model, and the appropriate EECP pressure amplitude could provide patients with the best benefits. The proposed control system could generate satisfied hemodynamic effects even with noise, demonstrating its feasibility and robustness. It is also easy to apply with high accuracy, and may be the effective solutions for developing intelligent and personalized EECP devices.

Effect of Naoxintong Capsule on Microglia and Proteomics of Cortex After Myocardial Infarction in Rats.

Neuroinflammation caused by microglia in the central nervous system (CNS) is observed after myocardial infarction (MI). However, the inflammatory response mechanism remains unclear. BuChang Naoxintong capsule (NXT) is a Chinese medicine for treating ischemic cardio-cerebrovascular diseases, requiring more studies to understand the pharmacodynamic mechanism. Permanent ligation of the left anterior descending coronary artery (LAD) was performed in rats. Additionally, histopathological staining in the left ventricular (LV) and immunofluorescence within the brain cortex after 1 d and 7 d of MI were performed to determine the NXT pharmacodynamic action and best administration dosage. Proteomics helped obtain the essential proteins related to neuroinflammation and MI in the heart and brain tissue after 7 d of MI. Based on TTC, HE, Masson, and immunofluorescence staining results of CD206 and IBA-1, NXT demonstrated a better pharmacodynamic action towards myocardial injury and neuroinflammation after 7 d of MI. Moreover, the human equivalent dosage of NXT (220 mg/kg) became the best administration dose. The proteome bioinformatics analysis in the LV and brain cortex was performed. Thus, the elongation of very long-chain fatty acids protein 5 (ELOVL5) and ATP-binding cassette subfamily G member 4 (ABCG4) became critical proteins related to MI and neuroinflammation. The western blotting results indicated that ABCG4 expression possessed the same trend as the proteomics results. The auto-dock results revealed that ABCG4 had a good binding ability with Ferulic acid, Paeoniflorin, and Tanshinone II A, the key ingredients of NXT. The cellular thermal shift assay results demonstrated that ABCG4 showed better thermal stability post-NXT treatment. NXT can improve myocardial injury, such as heart infarct size, pathological injury, myocardial fibrosis, and inflammatory cell infiltration. Additionally, brain neuroinflammation induced by microglia after MI affects the expression and structure of ABCG4. Thus, ABCG4 could be the key protein associated with MI and neuroinflammation.

LOX-1 variants modulate the severity of cardiovascular disease: state of the art and future directions.

Atherosclerosis is one of the major causes of cerebral infarction and many other ischemic cardio-cerebrovascular diseases. Although large randomized clinical trials have highlighted the impressive benefits of lipid-lowering therapies, the 50-70% of patients who have achieved their lipid-lowering goal remain at high cardiovascular disease risk. For this reason, there is a need to investigate other markers of atherosclerosis progression. LOX-1 is a scavenger receptor that accepts oxidized low-density lipoproteins as major ligand and internalizes it by endocytosis favoring its retention in subendothelial layer and triggering a wide variety of proatherogenic events. However, other factors such as cytokines, shear stress, and advanced glycation end-products can upregulate LOX-1. LOX-1 is encoded by the OLR1 gene, located in the p12.3-p13 region of chromosome 12. OLR1 gene has different isoforms induced by splicing, or single-nucleotide polymorphisms(SNPs). According to some authors, the expression of these isoforms induces a different effect on atherosclerosis and cardiovascular disease. In particular, LOXIN, an isoform lacking part of the functional domain, exerts an important role in atherosclerosis protection. In other cases, studies on SNPs showed an association with more severe forms, like in the case of 3'UTR polymorphisms. The knowledge of these variants can give rise to the development of new preventive therapies and can lead to the identification of subjects at greater risk of cardiovascular event. In this review, we reported the state of the art regarding SNPs with known effects on OLR1 splicing and how LOX-1 variants modulate the severity of cardiovascular disease.

Association Between Migraine and Ischemic Cardio-Cerebrovascular Disease (CCVD) and Effects of Triptans and Ergotamine on the Risk of Ischemic CCVD in Patients with Migraine in the Korean NHIS-HEALS Cohort.

Triptans and ergotamine are commonly used to treat migraine, a risk factor for ischemic stroke. This study aimed to investigate the association between migraine and ischemic cardio-cerebrovascular disease (CCVD). Further analyses were performed to examine whether symptom-relieving treatment of migraine with triptans and ergotamine reduces ischemic CCVD in migraineurs. Participants from the Korean NHIS-HEALS cohort database were divided into patients reporting headache without migraine (HA), migraineurs who received at least one prescription for triptans or ergotamine (TE), and migraineurs who were prescribed neither triptans nor ergotamine (NTNE). Ischemic CCVDs comprised ischemic cerebrovascular diseases and cardiovascular diseases. Using cox proportional hazards regression models, primary and secondary analysis for risk of ischemic CCVDs was compared. Among 62,272 patients diagnosed with migraine or HA, men with migraine or HA numbered 14,747 and 8935, respectively, while the numbers of women were 27,836 and 10,754, respectively. The median follow-up was 6.65 years. The overall incidence rate of CCVDs was 4728/38,590 (12.25%) in females and 3158/23,682 (13.33%) in males. Compared with the HA group, the hazard ratios (HRs) (95% CIs) of the TE and NTNE groups for ischemic CCVDs were 1.18 (1.01-1.39) and 1.39 (1.28-1.50), respectively, in males, and 1.22 (1.09-1.37) and 1.53 (1.42-1.65), respectively, in females, after full adjustment for confounding variables. Compared with the NTNE group, the HRs (95% CIs) of the TE group for ischemic CCVDs were 0.86 (0.73-0.999) in males and 0.80 (0.72-0.88) in females. Migraine increased the risk of ischemic CCVDs in both sexes, and migraineurs treated with triptans and ergotamine were at lower risk of ischemic CCVDs than migraineurs who did not take those medications, especially in women.

Comparative Muscle Tolerability of Different Types and Intensities of Statins: A Network Meta-Analysis of Double-Blind Randomized Controlled Trials.

The benefits of statins for ischemic cardio-cerebrovascular diseases are well known. However, concerns around muscle adverse events still exist. We therefore aimed to compare the muscle safety of individual statins in adults. PubMed, Embase, Cochrane Central Register of Controlled Trials and Web of Science were searched to include double-blind randomized controlled trials (RCTs) comparing one statin with another or with control treatment. Pairwise meta-analyses and network meta-analyses were undertaken with Stata 14.0 software. Relative risk (RR) with 95% confidence intervals (CIs) was adopted for each outcome. A total of 83 RCTs were included. In the pairwise meta-analysis, statins were significantly associated with only a slight increase in muscle symptoms compared with control (RR=1.05; 95% CI=1.01-1.09). In the drug-level network meta-analyses, no statistically significant difference was found between individual statins in the incidence of muscle symptoms, myalgia, myopathy, rhabdomyolysis, creatine kinase (CK) >10 times the upper limit of normal (ULN) or discontinuation due to muscle adverse events. In the dose-level network meta-analyses, there were no statistically significant dose-dependent effects on any outcomes except that moderate-intensity statins had a higher incidence of muscle symptoms than control (RR=1.13; 95% CI=1.01-1.27). Moderate simvastatin (RR=6.57; 95% CI=1.26-34.41) and moderate pravastatin (RR=5.96; 95% CI=1.00-35.44) had a statistically significantly higher incidence of CK >10×ULN compared with moderate atorvastatin. Lipophilic statins and statins metabolized by liver cytochrome P450 3A4 were not associated with an increased risk of muscle adverse events. Statins may be generally safe on muscle. Moderate atorvastatin may be superior to equivalent simvastatin and pravastatin in muscle tolerability.

Therapeutic targets by traditional Chinese medicine for ischemia-reperfusion injury induced apoptosis on cardiovascular and cerebrovascular diseases

Traditional Chinese medicine (TCM) has a significant role in treating and preventing human diseases. Ischemic heart and cerebrovascular injuries are two types of diseases with different clinical manifestations with high prevalence and incidence. In recent years, it has been reported that many TCM has beneficial effects on ischemic diseases through the inhibition of apoptosis, which is the key target to treat myocardial and cerebral ischemia. This review provides a comprehensive summary of the mechanisms of various TCMs in treating ischemic cardiovascular and cerebrovascular diseases through anti-apoptotic targets and pathways. However, clinical investigations into elucidating the pharmacodynamic ingredients of TCM are still lacking, which should be further demystified in the future. Overall, the inhibition of apoptosis by TCM may be an effective strategy for treating ischemic cardio-cerebrovascular diseases.

Zedoarondiol inhibits atherosclerosis by regulating monocyte migration and adhesion via CXCL12/CXCR4 pathway

Atherosclerosis (AS) is an essential pathological changes of ischemic cardio-cerebrovascular disease, and monocyte migration and adhesion to endothelial cells are the critical pathological process in AS. Our previous studies demonstrated a beneficial effect of zedoarondiol in AS, but whether the mechanism is associated with monocyte migration and adhesion to endothelial cells remains unclear. In this study, we investigated whether the anti-atherosclerotic effects of zedoarondiol were associated with decreasing migration and adhesion of monocytes. The oil red O staining demonstrated that zedoarondiol ameliorated AS plaques in en face aorta and aortic root of apolipoprotein E gene knocked (apoE-/-) mice. In vitro, zedoarondiol decreased human monocytic macrophage-like cell line (THP-1) monocytes migration and adhesion to endothelial cells. Single-cell RNA sequencing analysis (scRNA-seq) in mice indicated that zedoarondiol decreased monocytes adhesion to endothelial cells by regulating CXC chemokine ligand 12/CXC chemokine receptor 4 (CXCL12/CXCR4) pathway, which was verified by Western blot of THP-1 monocytes；zedoarondiol also decreased the expressions of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT) and nuclear factor-kappa B (NF/κB), the downstream proteins of CXCL12/CXCR4 pathway. In conclusion, zedoarondiol ameliorated AS plaque and inhibited monocyte migration and adhesion to endothelial cells via regulating CXCL12/CXCR4 pathway, suggesting that zedoarondiol might be a new promising drug for AS.

Promoting Angiogenesis Effect and Molecular Mechanism of Isopropyl Caffeate (KYZ), a Novel Metabolism-Derived Candidate Drug, Based on Integrated Network Pharmacology and Transgenic Zebrafish Models.

Aim of the study: Ischemic diseases have a huge impact on people’s health, which can cause blood supply blockage or restriction in specific tissues. Researchers must develop novel drugs with great efficacy and low toxicity for the prevention and treatment of such diseases. Isopropyl caffeic acid (KYZ) was one of the metabolites of caffeic acid in vivo. This study is to explore the protective effect and mechanism of KYZ on ischemic disease from the perspective of angiogenesis in vivo and in vitro, providing support for the treatment of ischemic diseases and the discovery of a new candidate drug. Methods: The network pharmacology and molecular docking were used to predict the targets of KYZ. In addition, the effects of KYZ on damaged and normal blood vessels were evaluated using the Tg (fli1: EGFP) transgenic zebrafish. The HUVECs model was used to study the effects of KYZ on proliferation, migration, and tube formation. The same dosage of caffeic acid (CA) was also administered in vitro and in vivo at the same time to assess the pharmacodynamic difference between the two compounds. Western Blot and ELISA methods were used to detect the expression of related target proteins. Results: The result from the network pharmacology indicated that the targets of KYZ were related to angiogenesis. It was also found that KYZ could repair the vascular damage induced by the PTK787 and promote the growth of subintestinal vessels in normal zebrafish. The result also indicated that KYZ’s angiogenic ability is better than the precursor compound CA. In HUVECs, KYZ could promote cell proliferation, migration, and tube formation. Further mechanistic study suggested that the KYZ could induce the release of VEGF factor in HUVECs, up-regulate the expression of VEGFR2, and activate the PI3K/AKT and MEK/ERK signaling pathways. Conclusions: These data show that KYZ may promote angiogenesis through VEGF, PI3K/AKT, and MEK/ERK signaling pathways, suggesting that KYZ exhibited great potential in the treatment of ischemic cardio-cerebrovascular diseases.

Pro-Angiogenic Effects of Essential Oil from Perilla frutescens and Its Main Component (Perillaldehyde) on Zebrafish Embryos and Human Umbilical Vein Endothelial Cells.

PurposePerilla frutescens (L.) Britt., a traditional edible-medicinal herb in China, has been used to treat cardiovascular and cerebrovascular (cardio-cerebrovascular) diseases for thousands of years. However, knowledge of the mechanisms underlying the effects of essential oil from P. frutescens (EOPF) in the treatment of cardio-cerebrovascular diseases is lacking. The promotion of angiogenesis is beneficial in the treatment of ischemic cardio-cerebrovascular diseases. The current study investigated the pro-angiogenic role of EOPF and its main component perillaldehyde in sunitinib-injured transgenic Tg (flk1:EGFP) zebrafish embryos and human umbilical vein endothelial cells (HUVECs) for the first time.Materials and MethodsThe pro-angiogenic effects of EOPF and perillaldehyde were observed in vivo using transgenic Tg (flk1:EGFP) zebrafish embryos and in vitro using HUVECs. Cell viability, proliferation, migration, tube formation, and protein levels were detected by MTT, EdU staining, wound healing, transwell chamber, and Western blot assays, respectively.ResultsEOPF and perillaldehyde exerted a significant stimulatory effect on the formation of zebrafish intersegmental vessels (ISVs). Moreover, EOPF and perillaldehyde promoted proliferation, migration, and tube formation in sunitinib-treated HUVECs. Additionally, our findings uncovered that the pro-angiogenic effects of EOPF and perillaldehyde were mediated by increases in the expression ratios of p-ERK1/2 to ERK1/2 and Bcl-2 to Bax.ConclusionThe present study is the first report to provide clear evidence that EOPF and perillaldehyde promote angiogenesis by stimulating repair of sunitinib-injured ISVs in zebrafish embryos and promoting proliferation, migration, and tube formation in sunitinib-injured HUVECs. The underlying mechanisms are related to increased p-ERK1/2 to ERK1/2 and Bcl-2 to Bax expression ratios. EOPF and perillaldehyde may be used in the treatment of cardio-cerebrovascular diseases, which is consistent with the traditional application of P. frutescens.

Danhong injection alleviates cerebral ischemia/reperfusion injury by improving intracellular energy metabolism coupling in the ischemic penumbra

Danhong injection (DHI) is a compound Chinese medicine widely used in China for treatment of ischemic cardio-cerebrovascular diseases. However, limited data are available regarding the protective effect of DHI on the ischemic penumbra in ischemic stroke. This study aimed to investigate the effect of intravenous DHI on neuronal injure in the ischemic penumbra after cerebral ischemia/reperfusion (CI/R), focusing especially on the involvement of intracellular energy metabolism coupling. Male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion for 60 min followed by reperfusion with or without intravenous DHI (0.5, 1.0, or 2.0 mL/kg) once daily for 7 days. Post-treatment with DHI ameliorated neurological defects, diminished cerebral infarction, alleviated cerebral edema, improved microcirculatory perfusion after 7days of reperfusion, and inhibited apoptosis and enhanced neuronal survival in the ischemic penumbra. In addition, DHI significantly ameliorated oxidative stress, reduced DNA damage, and inhibited the activation of PARP1/AIF pathway, thereby restoring cytoplasmic glycolytic activity. Furthermore, this drug increased PDH activity by inhibiting the HIF1α/PDK1 signaling pathway, thus eliminating the inhibitory effect of CI/R on mitochondrial metabolism. The results of this study suggest that DHI can alleviate cerebral edema after CI/R and rescue the ischemic penumbra, and these protective effects are due to the regulation of intracellular energy metabolic coupling.

Silencing lncRNA AK136714 reduces endothelial cell damage and inhibits atherosclerosis.

Atherosclerosis correlates with ischemic cardio-cerebrovascular diseases such as coronary heart disease. Long non-coding RNAs (lncRNAs) can promote atherosclerosis. We investigated the role of the lncRNA AK136714 in atherosclerosis. Compared with the healthy group, lncRNA AK136714 expression was elevated in the plaque and plasma of the atherosclerosis patients in a GEO dataset. AK136714 silencing inhibited atherosclerosis formation in ApoE-/- mice. AK136714 silencing also protected the endothelial barrier and inhibited endothelial cell inflammation. In vitro assays showed that knockdown of AK136714 suppressed the inflammatory response and apoptosis in human umbilical vein endothelial cells (HUVECs). Moreover, AK136714 was found to bind directly to HuR to increase the mRNA stability of TNF-α, IL-1β and IL-6 mRNAs. In addition, AK136714 promoted the transcription of Bim. This study expands our understanding of the role of lncRNA AK136714 in atherosclerosis and provides potential drug targets for the treatment of atherosclerosis.

Classification of red blood cell aggregation using empirical wavelet transform analysis of ultrasonic radiofrequency echo signals

Grading red blood cell (RBC) aggregation is important for the early diagnosis and prevention of related diseases such as ischemic cardio-cerebrovascular disease, type II diabetes, deep vein thrombosis, and sickle cell disease. In this study, a machine learning technique based on an adaptive analysis of ultrasonic radiofrequency (RF) echo signals in blood is proposed, and its feasibility for classifying RBC aggregation is explored. Using an adaptive empirical wavelet transform (EWT) analysis, the ultrasonic RF signals are decomposed into a series of empirical mode functions (EMFs); then, dominant empirical mode functions (DEMFs) are selected from the series. Six statistical characteristics, including the mean, variance, median, kurtosis, root mean square (RMS), and skewness are calculated for the locally normalized DEMFs, aiming to form primary feature vectors. Random forest (RDF) and support vector machine (SVM) classifiers are trained with the given feature vectors to obtain prediction models for RBC classification. Ultrasonic RF echo signals are acquired from five groups of six types of porcine blood samples with average numbers of aggregated RBCs of 1.04, 1.20, 1.83, 2.31, 2.72, and 4.28, respectively, to test the classification performance of the proposed method. The best subset with regard to the variance, kurtosis, and RMS is determined according to the maximum accuracy based on the RDF and SVM classifiers. The classification accuracies are 84.03 ± 3.13% for the RDF classifier, and 85.88 ± 2.99% for the SVM classifier. The mean classification accuracy of the SVM classifier is 1.85% better than that of the RDF classifier. In conclusion, the machine learning method is useful for the discrimination of varying degrees of RBC aggregation, and has potential for use in characterizing and monitoring the RBC aggregation in vessels.

Epidemiology of breast cancer, a paradigm of the “common soil” hypothesis

Breast cancer is the leading cause of death in women aged 20-50 years, with some geographical difference. The yearly incidence of the disease is increasing while the related mortality is steadily decreasing. Breast cancer is associated not only with specific hormones or factors related with reproduction, but mostly to more general environmental factors, linked to socioeconomic conditions and lifestyles (smoking, stress, physical exercise and particularly dietary habits). The latter, indeed, are risk factors or conditions common to hormone-dependent tumors and other chronic degenerative disorders, such as ischemic cardio cerebro-vascular and neuro-degenerative disease. Breast cancer can indeed be considered as a paradigm of the so-called "common soil" concept, according to which the above mentioned conditions, although having different clinical manifestations, share some pathogenetic mechanisms and risk factors and intermediate predisposing phenotypes (see Type2 diabetes, metabolic syndrome or obesity). In an epidemiological perspective, evidence has been accumulated on the common response of breast cancer and cardiovascular disorders to healthy lifestyles and in particular to the beneficial effects of a close adhesion to the Mediterranean dietary model. The latter would mainly be effective thanks to its anti-inflammatory properties, thus controlling the subclinical condition of low-grade inflammation, a common risk factor of all the "common soil" disorders. Results from the prospective cohort of the Moli-sani Study (nearly 25,000 adults from the general population of the Southern Italy region of Molise) are highly suggestive in this context. In a public health perspective, the "common soil" hypothesis may thus promote the application of preventive strategies, particularly targeting lifestyles, for a broad spectrum of widely prevalent disorders, ranging from breast cancer to myocardial infarction or cognitive impairment conditions.

Depressed Serum 25-Hydroxyvitamin D Levels Increase Hospital Stay and Alter Glucose Homeostasis in First-ever Ischemic Stroke.

Vitamin D deficiency is internationally recognized among the potentially modifiable risk factors for ischemic cardio-cerebrovascular diseases. However, the association between vitamin D deficiency and stroke morbidity or mortality remains insufficiently known. Our aim is to investigate their relevance to 25-hydroxyvitamin D [25(OH) D] levels and clinical severity and outcome after 3 months in first-ever ischemic stroke. Retrospective analysis of 356 consecutive patients in first-ever ischemic stroke between 2013 and 2015. Serum 25(OH) D levels were measured at baseline. Stroke severity was assessed at admission using the National Institutes of Health Stroke Scale (NIHSS) score. Functional outcome after 3 months of onset was evaluated using the modified Rankin scale (mRS). Among the 356 enrolled patients, HbA1c was higher in insufficiency/deficiency group than that in the sufficiency group (6.3 ± 1.7 vs. 5.9 ± 1.1, p =0.015). The hospital stay was longer in insufficiency/deficiency group than that in the sufficiency group (11 (8-17) vs. 9.5 (7-13), p = 0.035). There was a significant inversed trend between serum 25(OH) D levels and hospital stay (OR 0.960, P = 0.031), using logistic regression. 25(OH)D levels are associated with glucose homeostasis, 25(OH) D contributes to increase the length of hospital stay. Low serum 25-OHD level is an independent predictor for hospital stay in first-ever ischemic stroke. Vitamin D deficiency did not predict functional outcome in the span of 3 months.

The Role of Oxidative Stress in Common Risk Factors and Mechanisms of Cardio-Cerebrovascular Ischemia and Depression.

The public health sector faces a huge challenge as a result of the high prevalence and burden of disability caused by ischemic cardio-cerebrovascular disease (CVD) and depression. Although studies have explored the underlying mechanisms and potential therapies to address conditions, there is no treatment breakthrough, especially for depression which is highly influenced by social stressors. However, accumulating evidence reveals that CVD and depression are correlated and share common risk factors, particularly obesity, diabetes, and hypertension. They also share common mechanisms, including oxidative stress (OS), inflammation and immune response, cell death signaling pathway, and microbiome-gut-brain axis. This review summarizes the relationship between ischemic CVD and depression and describes the interactions among common risk factors and mechanisms for these two diseases. In addition, we propose that OS mediates the crosstalk between these diseases. We also reveal the potential of antioxidants to ameliorate OS-related injuries.

Associations between miR-146a rs2910164 polymorphisms and risk of ischemic cardio-cerebrovascular diseases.

Background:Many studies investigated the association between miR-146a rs2910164 polymorphisms and risk of ischemic cardio-cerebrovascular diseases. However, the results were inconsistent.Methods:We searched the PubMed, EMBASE, Cochrane library, Web of Science, Chinese National Knowledge Infrastructure, VIP, and Wanfang databases for appropriate studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the associations. Heterogeneity, sensitivity, and publication bias were conducted to measure the robustness of our findings.All analyses were based on previous published studies, thus, no ethical approval and patient consent are required.Results:We conducted a meta-analysis to evaluate the relationship between miR-146a rs2910164 polymorphisms and risk of ischemic cardio-cerebrovascular diseases. A total of 26 related studies involving 11,602 cases and 14,016 controls were identified and included in our meta-analysis. After considering the heterogeneity of the global analysis, we inferred that rs2910164 polymorphisms were associated with a lower risk of coronary heart disease (CHD) significantly in all genetic models. In addition, it was also found that the miR-146a rs2910164 polymorphisms were associated with the low risk of ischemic cardio-cerebrovascular diseases in large sample size subgroup analysis.Conclusion:These results indicate that miR-146a rs2910164 polymorphisms were significantly associated with a lower risk of ischemic cardio-cerebrovascular. The miR-146a rs29101164 might be recommended as a predictor for susceptibility of ischemic cardio-cerebrovascular diseases.

Computer-assisted prediction of atherosclerotic intimal thickness based on weight of adrenal gland, interleukin-6 concentration, and neural networks.

ObjectiveAtherosclerosis (AS) is the main pathological basis of ischemic cardio-cerebrovascular diseases, and the intimal thickness (IT) of large arteries is regarded as a powerful evaluation indicator for AS. We established an effective neural network model for automatic prediction of the IT and analyzed the high-risk warning indicators of IT.MethodsThe weight of the left adrenal (WLA) was evaluated. The serum interleukin-6 (IL-6) concentration was measured by enzyme-linked immunosorbent assay. The statistical methods included neural network modeling, a cubic spline interpolation algorithm, Spearman’s rho test, and linear fit.ResultsThirty-seven rabbits were classified into a control group (n = 11), high-fat diet group (n = 13), and high-fat diet plus chronic stress group (n = 13). The neural network model was successfully established and verified by comparing the predicted IT with the actual IT. The high-risk warning indicator of IT was identified as follows: 0.445 g < WLA < 0.610 g and 60 ng/L< IL-6 < 80 ng/L.ConclusionsThe neural network model based on WLA and IL-6 could predict the IT of AS. When 0.445 g < WLA < 0.610 g and 60 ng/L < IL-6 < 80 ng/L, the risk to developing AS is very high.

Fibrinopeptide A induces C-reactive protein expression through the ROS-ERK1/2/p38-NF-κB signal pathway in the human umbilical vascular endothelial cells.

Atherosclerosis is a chronic inflammatory disease of the arterial wall. Inflammation causes endothelial injury and dysfunction, which is an initial step of atherosclerosis. Fibrinopeptide A (FPA) is a biomarker of the activation of the coagulation system, and a high concentration of FPA in the blood occurs in patients with ischemic cardiocerebrovascular diseases. The present research observed that FPA stimulated the generation of C-reactive protein (CRP), IL-1β, and IL-6 in human umbilical vascular endothelial cells (HUVECs); and anti-IL-1 β and anti-IL-6 neutralizing antibodies did not alter FPA-induced CRP expression in HUVECs. The subchronic administration of FPA into rats increased the plasma FPA and CRP levels. Further studies showed that FPA stimulated superoxide anion generation, activated ERK1/2 and p38, promoted nuclear factor κB (NF-κB) nuclear translocation, and raised the NF-κB level in the nuclei of HUVECs. Antioxidant N-acetylcysteine (NAC), complex II inhibitor thenoyltrifluoroacetone (TTFA), and NADPH oxidase inhibitor diphenyleneiodonium (DPI) inhibited FPA-stimulated generation of superoxide anion, and NAC reduced FPA-induced expressions of the phosphorylated ERK1/2 and p38. NAC, TTFA, DPI, inhibitors of ERK1/2, p38, and NF-κB all downregulated FPA-induced CRP expression. These results indicate that FPA induces CRP expression in HUVECs via the ROS-ERK1/2/p38-NF-κB signal pathway. Moreover, this is the first report that FPA produces a proinflammatory effect on the vascular endothelial cells.