Ethoxyquin, a Lipid Peroxidation Inhibitor, Has Protective Effects against White Matter Lesions in a Mouse Model of Chronic Cerebral Hypoperfusion.

White matter lesions induced by chronic cerebral hypoperfusion can cause vascular dementia; however, no appropriate treatments are currently available for these diseases. In this study, we investigated lipid peroxidation, which has recently been pointed out to be associated with cerebrovascular disease and vascular dementia, as a therapeutic target for chronic cerebral hypoperfusion. We used ethoxyquin, a lipid-soluble antioxidant, in a neuronal cell line and mouse model of the disease. The cytoprotective effect of ethoxyquin on glutamate-stimulated HT-22 cells, a mouse hippocampal cell line, was comparable to that of a ferroptosis inhibitor. In addition, the administration of ethoxyquin to bilateral common carotid artery stenosis model mice suppressed white matter lesions, blood-brain barrier disruption, and glial cell activation. Taken together, we propose that the inhibition of lipid peroxidation may be a useful therapeutic approach for chronic cerebrovascular disease and the resulting white matter lesions.

Protective mechanism of Paeonol on central nervous system.

Cerebrovascular diseases involve neuronal damage, resulting in degenerative neuropathy and posing a serious threat to human health. The discovery of effective drug components from natural plants and the study of their mechanism are a research idea different from chemical synthetic medicines. Paeonol is the main active component of traditional Chinese medicine Paeonia lactiflora Pall. It widely exists in many medicinal plants and has pharmacological effects such as anti-atherosclerosis, antiplatelet aggregation, anti-oxidation, and anti-inflammatory, which keeps generally used in the treatment of cardiovascular and cerebrovascular diseases. Based on the therapeutic effects of Paeonol for cardiovascular and cerebrovascular diseases, this article reviewed the pharmacological effects of Paeonol in Alzheimer's disease, Parkinson's disease, stroke, epilepsy, diabetes encephalopathy, and other neurological diseases, providing a reference for the research of the mechanism of Paeonol in central nervous system diseases.

Research Progress in Pharmacological Effects and Mechanisms of Angelica sinensis against Cardiovascular and Cerebrovascular Diseases.

Angelica sinensis (Oliv.) Diels (A. sinensis) is a medicinal and edible values substance, which could promote blood circulation and enrich blood. It possesses rich chemical components and nutrients, which have significant therapeutic effects on cardiovascular and cerebrovascular diseases. It is commonly used for the prevention and treatment of cardiovascular and cerebrovascular diseases in the elderly, especially in improving ischemic damage to the heart and brain, protecting vascular cells, and regulating inflammatory reactions. This article reviews the main pharmacological effects and clinical research of A. sinensis on cardiovascular and cerebrovascular diseases in recent years, explores the effect of its chemical components on cardiovascular and cerebrovascular diseases by regulating the expression of functional proteins and inhibiting inflammation, anti-apoptosis, and antioxidant mechanisms. It provides a reference for further research on A. sinensis and the development of related drugs. It provides a new reference direction for the in-depth research and application of A. sinensis in the prevention, improvement, and treatment of cardiovascular and cerebrovascular diseases.

Nanozyme-Enabled Treatment of Cardio- and Cerebrovascular Diseases.

Cardio- and cerebrovascular diseases are two major vascular-related diseases that lead to death worldwide. Reactive oxygen species (ROS) play a vital role in the occurrence and exacerbation of diseases. Excessive ROS induce cellular context damage and lead to tissue dysfunction. Nanozymes, as emerging enzyme mimics, offer a unique perspective for therapy through multifunctional activities, achieving essential results in the treatment of ROS-related cardio- and cerebrovascular diseases by directly scavenging excess ROS or regulating pathologically related molecules. This review first introduces nanozyme-enabled therapeutic mechanisms at the cellular level. Then, the therapies for several typical cardio- and cerebrovascular diseases with nanozymes are discussed, mainly including cardiovascular diseases, ischemia reperfusion injury, and neurological disorders. Finally, the challenges and outlooks for the application of nanozymes are also presented. This review will provide some instructive perspectives on nanozymes and promote the development of enzyme-mimicking strategies in cardio- and cerebrovascular disease therapy.

Vitamin D as therapeutic modulator in cerebrovascular diseases: a mechanistic perspectives.

Vitamin D deficiency has been linked to several major chronic diseases, such as cardiovascular and neurodegenerative diseases, diabetes, and cancer, linked to oxidative stress, inflammation, and aging. Vitamin D deficiency appears to be particularly harmful to the cardiovascular system, as it can cause endothelial dysfunctioning and vascular abnormalities through the modulation of various downstream mechanisms. As a result, new research indicates that therapeutic approaches targeting vitamin D inadequacies or its significant downstream effects, such as impaired autophagy, abnormal pro-inflammatory and pro-oxidant reactions, may delay the onset and severity of major cerebrovascular disorders such as stroke and neurologic malformations. Vitamin D modulates the various molecular pathways, i.e., Nitric Oxide, PI3K-Akt Pathway, cAMP pathway, NF-kB Pathway, Sirtuin 1, Nrf2, FOXO, in cerebrovascular disorder. The current review shows evidence for vitamin D's mitigating or slowing the progression of these cerebrovascular disorders, which are significant causes of disability and death worldwide.

[Research progress in pharmacological effectsand mechanism of Fel Ursi against cardiovascular and cerebrovascular diseases].

Fel Ursi is a dried product obtained from the gallbladder of Ursidae animals, such as Selenarctos thibetanus or Ursus arctos, through gallbladder surgery for bile drainage. It is one of the rare animal medicinal materials in China and is known for its therapeutic effects, including clearing heat, removing toxins, extinguishing wind, relieving spasms, clearing the liver, and improving vision. Research has also found that Fel Ursi has pharmacological effects against cardiovascular and cerebrovascular diseases, such as anti-inflammatory, anti-apoptotic, and antioxidant stress properties. Recently, numerous studies have confirmed the close relationship between cardiovascular and cerebrovascular diseases and the gut microbiota as well as gut metabolites. Fel Ursi contains bile acid components that may have bidirectional regulatory effects on the gut microbiota and gut metabolites. This aspect could represent a potential therapeutic pathway for Fel Ursi in the treatment of cardiovascular and cerebrovascular diseases. This article comprehensively summarized relevant literature in China and abroad, reviewed the research progress on the pharmacological effects of Fel Ursi against cardiovascular and cerebrovascular diseases, and explored the impact of Fel Ursi on gut microbiota and gut metabolites, thereby aiming to provide references for further in-depth research and clinical application of Fel Ursi.

Application of Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping Score for Efficacy of Clopidogrel: Secondary Analysis of the CHANCE Trial.

BACKGROUND AND PURPOSE: The age, body mass index, chronic kidney disease, diabetes, and genotyping (ABCD-GENE) score is a validated risk score integrating CYP2C19 genotypes with clinical risk factors influencing clopidogrel response that would allow the more precise identification of subjects at risk for high platelet reactivity and adverse clinical outcomes. Our objective was to further verify application of the ABCD-GENE score and investigate appropriate cutoff value in patients with minor stroke or transient ischemic attack. METHODS: In this post-analysis of the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), the ABCD-GENE score was calculated for all patients enrolled in this study. By using the proposed cutoff of 10, patients were stratified as being at high risk for high platelet reactivity or not. We further categorized the ABCD-GENE score to 0 to 5, 6 to 24, and >24 to investigate the cutoff value of this scale in clinical application. Stroke recurrence at 3 months was considered as the primary outcome. RESULTS: Among a total of 2923 patients with minor stroke/transient ischemic attack, there were 2273 (77.76%) with ABCD-GENE score <10 and 650 (22.24%) patients with ABCD-GENE score ≥10. Compared with the aspirin alone, hazard ratios (95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 0.70 (0.54-0.91) and 0.76 (0.46-1.24), among patients of ABCD-GENE scores <10 and ABCD-GENE scores ≥10, respectively. Stratified analyses by ABCD-GENE score 0 to 5, 6 to 24, and >24, hazard ratios of the clopidogrel-aspirin therapy for stroke recurrence were 0.57 (95% CI, 0.38-0.85), 0.78 (0.58-1.06), and 1.20 (0.44-3.28) (P value for trend=0.0052). CONCLUSIONS: Among Chinese minor stroke/transient ischemic attack population, the efficacy of clopidogrel-aspirin therapy was decreased in patients with higher ABCD-GENE score. Our study suggests that CYP2C19 genotypes and clinical risk factors can be integrated by ABCD-GENE score to estimate the efficacy of clopidogrel-aspirin therapy.

Progress in Stimuli-Responsive Biomaterials for Treating Cardiovascular and Cerebrovascular Diseases.

Cardiovascular and cerebrovascular diseases (CCVDs) describe abnormal vascular system conditions affecting the brain and heart. Among these, ischemic heart disease and ischemic stroke are the leading causes of death worldwide, resulting in 16% and 11% of deaths globally. Although several therapeutic approaches are presented over the years, the continuously increasing mortality rates suggest the need for more advanced strategies for their treatment. One of these strategies lies in the use of stimuli-responsive biomaterials. These "smart" biomaterials can specifically target the diseased tissue, and after "reading" the altered environmental cues, they can respond by altering their physicochemical properties and/or their morphology. In this review, the progress in the field of stimuli-responsive biomaterials for CCVDs in the last five years, aiming at highlighting their potential as early-stage therapeutics in the preclinical scenery, is described.

The interaction among OSA, CPAP, and medications in patients with comorbid OSA and cardiovascular/cerebrovascular disease: a randomized controlled trial.

BACKGROUND: Most patients with comorbid sleep apnea (OSA), cardiovascular (CV) disease, and/or cerebrovascular (CeV) disease simultaneously take medications. Whether OSA and continuous positive airway pressure (CPAP) interact with CV/CeV medications remains unknown. This study aimed to determine the interaction among OSA, CPAP, and CV/CeV medications; the effects of medications on major adverse cardiac and cerebrovascular events, and survival in patients with comorbid OSA and CV/CeV. METHODS: This was a post hoc analysis of the data from one center of the Sleep Apnea Cardiovascular Endpoints Study. Participants (aged 45-75 years) with comorbid OSA and CV/CeV were randomized to receive usual care with or without CPAP from December 2008 to November 2013. The primary endpoint was death and the secondary endpoint was a composite of death, myocardial infarction, stroke, hospitalization for unstable angina, heart failure, and transient ischemic attack. RESULTS: In total, 131 patients were analyzed. Sixty-three were in the CPAP group and 68 were in the usual care group, 41 had good adherence to CPAP (65.1%), and the median follow-up time was 43.0 (35.0, 54.0) months. In Cox regression analysis, ACE inhibitors and nitrates were independent factors for decreased survival in patients with comorbid OSA and CV/CeV (chi-square = 22.932, P = 0.003; ACE inhibitors: OR 7.241, P = 0.048, 95% CI 1.016-51.628; nitrates: OR 18.012, P = 0.011, 95% CI 1.923-168.750). ACE inhibitors increased mortality and secondary endpoints in the CPAP group (chi-square = 4.134, P = 0.042) but not in patients with good CPAP adherence. Clopidogrel and nitrates decreased survival in usual care group (clopidogrel: chi-square = 5.312, P = 0.021; nitrates: chi-square = 6.417, P = 0.011), but not in CPAP group. CONCLUSIONS: OSA may predispose patients with CV/CeV and CV/CeV medications to a negative effect. CPAP treatment may neutralize the negative effects of OSA by relieving chronic intermittent hypoxia. Trial registration ClinicalTrials.gov (NCT00738179, first registration date: 20/08/2008).

Insights into the Explicit Protective Activity of Herbals in Management of Neurodegenerative and Cerebrovascular Disorders.

The longstanding progressive neurodegenerative conditions of the central nervous system arise mainly due to deterioration, degradation and eventual neuronal cell loss. As an individual ages, the irreversible neurodegenerative disorders associated with aging also begin to develop, and these have become exceedingly prominent and pose a significant burden mentally, socially and economically on both the individual and their family. These disorders express several symptoms, such as tremors, dystonia, loss of cognitive functions, impairment of motor activity leading to immobility, loss of memory and many more which worsen with time. The treatment employed in management of these debilitating neurodegenerative disorders, such as Parkinson's disease (which mainly involves the loss of dopaminergic neurons in the nigrostriatal region), Alzheimer's disease (which arises due to accumulation of Tau proteins causing diffusive atrophy in the brain), Huntington's disease (which involves damage of striatal and spinal neurons, etc.), have several adverse effects, leading to exploration of several lead targets and molecules existing in herbal drugs. The current review highlights the mechanistic role of natural products in the treatment of several neurodegenerative and cerebrovascular diseases such as Parkinson's disease, Alzheimer's disease, ischemic stroke and depression.

Antiplatelets and Anticoagulants in Ischemic Stroke,Transient Ischaemic Attack: A Practice Survey Among Singapore Neurologists.

PURPOSE: Evidence-based stroke clinical practice guidelines provide guidance as how to best manage patients with cerebrovascular disease. Where there are grey zones, the clinician decides what she/he feels is the most appropriate in that circumstance. This study was performed to determine how adult neurologists in Singapore would use antiplatelets(AP) and anticoagulants(AC) for their ischemic stroke patients in various settings where the evidence is uncertain. METHODS: A standardised questionnaire was sent to adult neurologists in Singapore. The questions evaluated their preferred type and dose of AP, use of heparin prior to initiating warfarin, and their preferred treatments in 6 different clinical scenarios. RESULTS: A total of 31/33 neurologists responded (93.9%). For long term secondary prevention, 71.0% preferred aspirin only, 22.6% clopidogrel/ticlopidine only, 6.5% aspirin plus dipyridamole. Anticoagulation with warfarin was initiated with a heparin bolus by 45.2%. AC were preferred by 80.6% for stroke in evolution, 80.6% for presumed basilar artery thrombosis, 54.8% for crescendo TIAs. For patients awaiting CEA, 58.1% preferred AP, 32.3% AC. For patients on preferred AP developing another cerebrovascular event with no new underlying cause, 48.4% would change AP, 25.8% would add another AP. For patients on adequate AC for non-cardioembolism developing another cerebrovascular event, 54.8% would add anti-platelet, 19.4% would increase AC. CONCLUSIONS: The widespread use of aspirin for long-term secondary prevention is similar to other countries. The variation in the use of antithrombotic agents in other settings may reflect the lack of sufficient evidence to guide therapy in the various specific stroke patient management scenarios. KEY WORDS: neurologist, practice, antiplatelet, anticoagulant, stroke, cerebrovascular disease.

[Expert consensus on clinical application of GBE50 Dispersible Tablets for ischemic cardiovascular and cerebrovascular diseases].

Ginkgo biloba Extract( GBE50) Dispersible Tablets is a new standardized prescription,which is widely used in the treatment of ischemic cardiovascular and cerebrovascular diseases. However,there are still many problems in its clinical application.Rational and safe use of GBE50 Dispersible Tablets is pivotal to the medication safety and clinical prognosis of patients. This consensus has been jointly formulated by clinical experts of traditional Chinese medicine and western medicine in cardiovascular and cerebrovascular diseases and followed the Manual for the Clinical Experts Consensus of Chinese Patent Medicine published by the China Association of Chinese Medicine. The present study identified clinical problems based on clinical investigation,searched the research papers according to PICO clinical problems,carried out evidence evaluation,classification,and recommendation by GRADE system,and reached the expert consensus with nominal group technique. The consensus combines evidence with expert experience. Sufficient evidence of clinical problems corresponds to " recommendations",while insufficient evidence to " suggestions". Safety issues of GBE50 Dispersible Tablets,such as indications,usage and dosage,and medication for special populations,are defined to improve clinical efficacy,promote rational medication,and reduce drug risks. This consensus needs to be revised based on emerging clinical issues and evidencebased updates in practical applications in the future.

Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: a systematic review and meta-analysis.

BACKGROUND: Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. METHODS: In this systematic review and meta-analysis, all randomised trials comparing P2Y12 inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease were evaluated for inclusion. On Dec 18, 2019, we searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, we reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients' features including the baseline condition determining study inclusion (ie, cerebrovascular, coronary, or peripheral artery disease), P2Y12 inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected. Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I2 index. This study is registered with PROSPERO (CRD42018115037). FINDINGS: A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y12 inhibitor (n=21 043) or aspirin (n=21 065) were included in our analyses. Patients who received a P2Y12 inhibitor had a borderline reduction for the risk of myocardial infarction compared with those who received aspirin (OR 0·81 [95% CI 0·66-0·99]; I2=10·9%). Risks of stroke (OR 0·93 [0·82-1·06]; I2=34·5%), all-cause death (OR 0·98 [0·89-1·08]; I2=0%), and vascular death (OR 0·97 [0·86-1·09]; I2=0%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR 0·90 [0·74-1·10]; I2=3·9%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. The number needed to treat to prevent one myocardial infarction with P2Y12 inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y12 inhibitor used. INTERPRETATION: Compared with aspirin monotherapy, P2Y12 inhibitor monotherapy is associated with a risk reduction for myocardial infarction and a comparable risk of stroke in the setting of secondary prevention. The benefit of P2Y12 inhibitor monotherapy is of debatable clinical relevance, in view of the high number needed to treat to prevent a myocardial infarction and the absence of any effect on all-cause and vascular mortality. FUNDING: Italian Ministry of Education.

Cytokines as therapeutic targets for cardio- and cerebrovascular diseases.

Despite major advances in prevention and treatment, cardiac and cerebral atherothrombotic complications still account for substantial morbidity and mortality worldwide. In this context, inflammation is involved in the chronic process leading atherosclerotic plaque formation and its complications, as well as in the maladaptive response to acute ischemic events. For this reason, modulation of inflammation is nowadays seen as a promising therapeutic strategy to counteract the burden of cardio- and cerebrovascular disease. Being produced and recognized by both inflammatory and vascular cells, the complex network of cytokines holds key functions in the crosstalk of these two systems and orchestrates the progression of atherothrombosis. By binding to membrane receptors, these soluble mediators trigger specific intracellular signaling pathways eventually leading to the activation of transcription factors and a deep modulation of cell function. Both stimulatory and inhibitory cytokines have been described and progressively reported as markers of disease or interesting therapeutic targets in the cardiovascular field. Nevertheless, cytokine inhibition is burdened by harmful side effects that will most likely prevent its chronic use in favor of acute administrations in well-selected subjects at high risk. Here, we summarize the current state of knowledge regarding the modulatory role of cytokines on atherosclerosis, myocardial infarction, and stroke. Then, we discuss evidence from clinical trials specifically targeting cytokines and the potential implication of these advances into daily clinical practice.

Management of LDL-cholesterol levels in patients with Diabetes Mellitus in Cardiology Practice: Real-life evidence of Under-treatment from the EPHESUS registry.

BACKGROUND AND AIMS: Effective treatment of high low-density lipoprotein cholesterol (LDL-C) levels has been shown to improve cardiovascular outcomes of patients with diabetes mellitus (DM). Herein, we aimed to provide insight to the real-life management of patients with DM in terms of LDL-C goal attainment and adherence to lipid management recommendations. Our objective was also to reveal the reasons of poor LDL-C goal attainment by assessing the perceptions of both physicians and patients. METHODS: We compared the diabetic and non-diabetic patients from the database of a nationwide registry conducted in cardiology outpatient clinics with regard to the demographic characteristics, educational status, comorbidities, medications, laboratory parameters and LDL-C goal attainment. Also, both the patients and attending physicians were surveyed to analyse perceptions and awareness of hypercholesterolemia. RESULTS: Of the 1868 consecutively enrolled patients, 873 (47%) had DM. Proportion of patients on statins was significantly lower in patients with DM (67.8% vs 55.3%; P < .001). The proportion of patients who attained LDL-C targets were lower among the diabetic patients (17.8% vs 15%; P = .06). The most common causes of the discontinuation of statin therapy were negative media coverage about statins (32.1%), and recommendations of physicians to stop the lipid lowering therapy (29.6%). Analysis of the physician survey revealed that the physicians could determine the off-target patients accurately (negative predictive value 98.4%) while the positive predictive value (48.8%) was low. The reasons for not attaining the LDL-C goals in diabetic patients were not prescription of statins (38%) and inadequate (eg low-dose, non-adherent) statin (28.3%) dosages. CONCLUSIONS: In real-life clinical cardiology practice, diabetic patients are far below the recommended LDL-C treatment goals. High-intensity statin treatment in diabetic population is still avoided because of the concerns about polypharmacy and drug interactions. Also, the inertia of physicians and even cardiologists is probably a major cause of refraining of prescription of optimal statin dosages.

The Attitude towards Polypills Questionnaire (APPQ): a phase I-III development and validation study in patients with cerebrovascular disease.

BACKGROUND AND PURPOSE: The polypill approach has been proposed to reduce patients' pill burden, increase medication adherence and lower stroke incidence. However, little is known about patients' attitudes towards polypills for cerebrovascular medication. METHODS: Based on the European Organization for Research and Treatment of Cancer Quality of Life Group questionnaire development guidelines, a questionnaire to measure patients' attitudes towards polypills for the secondary prevention of stroke (phase I-III) was developed. In phase I, issues were generated via literature review and interviews with patients and healthcare professionals. The issues were operationalized into items in phase II. In phase III the questionnaire was validated in a large single-centre sample, and test-retest and internal validity were evaluated. RESULTS: In phase I, 34 relevant issues were identified through literature search and interviews. Pre-testing the questionnaire indicated high applicability and comprehensibility. The final Attitudes towards Polypills Questionnaire was tested in N = 260 patients and showed a two-factor structure. The factors were labelled 'concerns' and 'benefits'. The scales showed acceptable and good internal validity (concerns, Cronbach's α = 0.85; benefits, α = 0.93), but the scales' test-retest validity was ambiguous. On a 0 to 3 rating scale, concerns were rated lower than benefits (mean 1.07, SD 0.69 vs. mean 1.87, SD 0.89). CONCLUSIONS: The Attitudes towards Polypills Questionnaire showed high comprehensibility and content validity to assess German language patients' attitudes towards a polypill medication. Our data and questionnaire may aid the implementation of polypill treatments in clinical practice and can be used in the design of future clinical trials on polypill therapy. Further validation of the questionnaire is advised.

Vitexin regulates Epac and NLRP3 and ameliorates chronic cerebral hypoperfusion injury.

Chronic cerebral hypoperfusion (CCH), as a critical factor of chronic cerebrovascular diseases, has greatly influenced the health of patients with vascular dementia. Vitexin, a flavone C-glycoside (apigenin-8-C-ß-D-glucopyranoside) that belongs to the flavone subclass of flavonoids, has been shown to possess antioxidant and anti-ischemic properties; however, the putative protective effects of vitexin on the CCH need further investigation. In the current study, the role of vitexin and its underlying mechanism were investigated with permanent bilateral common carotid artery occlusion (2VO) in rats as well as mouse hippocampal neuronal (HT22) cells with oxygen and glucose deprivation/reoxygenation (OGD/R) injury model. The results demonstrated that vitexin improved cognitive dysfunction as well as alleviated pathological neuronal damage in hematoxylin plus eosin (HE) and TUNEL results. The decreased levels of exchange protein directly activated by cAMP 1 (Epac1), Epac2, Ras-associated protein 1 (Rap1), and phospho-extracellular signal-regulated kinase (p-ERK) were reversed by vitexin in rats with CCH. Furthermore, this study indicated that vitexin alleviated CCH-induced inflammation injuries by reducing the expression of NOD-like receptor 3 (NLRP3), caspase-1, interleukin 1ß (IL-1ß), IL-6, and cleaved caspase-3. In vitro, vitexin increased the expression of Epac1 and Epac2, decreased the activation of the NLRP3-mediated inflammation, and improved cell viability. Taken together, our findings suggest that vitexin can reduce the degree of the progressing pathological damage in the cortex and hippocampus and inhibit further deterioration of cognitive function in rats with CCH. Epac and NLRP3 can be regulated by vitexin in vivo and in vitro, which provides enlightenment for the protection of CCH injury.

Unusual Presentation of Bilateral Carotid Artery Dissection: The Importance of Reasoning Outside the Box.

A bilateral internal carotid artery dissection presenting with atypical symptoms of cerebral hypoperfusion has been rarely reported, especially in the absence of obvious precipitating factors. A middle-aged woman presented to the emergency department with a 2-day-history of progressive left arm numbness and weakness, confusion, disorientation and clumsiness worsened by upright position. A cerebral hypoperfusion condition was hypothesized and confirmed by a CT angiography, which showed bilateral internal carotid dissection with uncertain etiology. Screening for predisposing conditions to spontaneous carotid arteries dissection was basically negative. Regarding potential precipitating factors, the patient had used an electric olive harvester days before symptoms onset, without any painful sensation or sudden sequelae. Portable harvesters in olive growing transmit vibrations to the hand-arm system but it remains to be elucidated if hand-arm vibrations can be implicated in vessels wall injury and dissection. Bilateral carotid artery dissection is an infrequent and life-threatening condition which can rarely present with non-specific symptoms of cerebral hypoperfusion. The absence of typical symptoms and known precipitating factors can made the diagnosis quite hard to achieve.

Neurological Complications of COVID-19: Underlying Mechanisms and Management.

COVID-19 is a severe respiratory disease caused by the newly identified human coronavirus (HCoV) Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The virus was discovered in December 2019, and in March 2020, the disease was declared a global pandemic by the World Health Organization (WHO) due to a high number of cases. Although SARS-CoV-2 primarily affects the respiratory system, several studies have reported neurological complications in COVID-19 patients. Headache, dizziness, loss of taste and smell, encephalitis, encephalopathy, and cerebrovascular diseases are the most common neurological complications that are associated with COVID-19. In addition, seizures, neuromuscular junctions' disorders, and Guillain-Barré syndrome were reported as complications of COVID-19, as well as neurodegenerative and demyelinating disorders. However, the management of these conditions remains a challenge. In this review, we discuss the prevalence, pathogenesis, and mechanisms of these neurological sequelae that are secondary to SARS-CoV-2 infection. We aim to update neurologists and healthcare workers on the possible neurological complications associated with COVID-19 and the management of these disease conditions.

[Research progress on Chinese medicinal material-derived active polypeptides against ischemic cardiovascular and cerebrovascular diseases].

Ischemic cardiovascular and cerebrovascular diseases threatening human health and survival have high morbidity and mortality. The common cause of them is reduced blood supply caused by vascular stenosis, atherosclerosis, and infarction. However,the pathological processes of ischemic cardiovascular and cerebrovascular diseases are complex, involving oxidative stress, calcium overload, inflammation, apoptosis, autophagy and other mechanisms. Protein drugs such as recombinant tissue plasminogen activator(rt-PA) and urokinase have been proved with excellent therapeutic effects and huge economic and social benefits in the clinical treatment and interventional therapy. Among them, peptide drugs have shown unique advantages and potential prospects owing to their strong biological activity, high target specificity, biochemical diversity, and low toxicity. Chinese medicinal materials, characterized by multi-component and multi-target therapy, have also shown excellent clinical efficacy against ischemic cardiovascular and cerebrovascular diseases. However, the research and development of related peptides in Chinese medicinal materials is at the initial stage. Therefore, this paper reviewed the targets and action mechanisms of a variety of Chinese medicinal material-derived polypeptides with activities against ischemic cardiovascular and cerebrovascular diseases, aiming to provide support for the in-depth research as well as the clinical development and application of these polypeptides.