Artery Occlusion Research Articles

Superior Cerebellar Artery Aneurysm in a Case of Moyamoya Disease: A Rare Entity

AbstractMoyamoya disease is a rare condition characterized by progressive narrowing and occlusion of internal carotid artery and other major arteries of the brain with formation of multiple collaterals. The incidence of aneurysm in moyamoya disease is higher than normal population. Treating the simultaneous pathology of aneurysm and moyamoya disease in an individual is a rare entity. A 35-year-old male presented with headache, loss of consciousness, and generalized tonic-clonic seizure with subarachnoid hemorrhage. Digital Subtraction angiography showed moyamoya disease with left superior cerebellar artery aneurysm. Rupture of aneurysm was suspected to be the source of subarachnoid hemorrhage. Patient underwent clipping of the left superior cerebellar artery aneurysm with encephalo-duro-arterio-myo-synangiosis. Patient survived the procedures. All patients with subarachnoid hemorrhage in moyamoya disease should undergo angiogram and aneurysm should be looked for carefully. The site of aneurysm and the risk for damaging the collaterals should be kept in mind while planning the surgery in such cases.

Ascending aortic aneurysm after acute aortic dissection in a case with systemic lupus erythematosus

A 50-year-old woman with systemic lupus erythematosus and a history of aortic arch replacement surgery for Stanford type A aortic dissection experienced a reoccurrence of an ascending aortic aneurysm and coronary artery occlusion. Computed tomography revealed that the aneurysm was compressing the superior vena cava and right atrium. The patient underwent urgent surgery to repair the aneurysm. This case highlights that aortic aneurysms can reoccur even after total arch replacement in systemic lupus erythematosus patients.

Brain Ischemic Tolerance Triggered by Preconditioning Involves Modulation of Tumor Necrosis Factor-α-Stimulated Gene 6 (TSG-6) in Mice Subjected to Transient Middle Cerebral Artery Occlusion

Ischemic preconditioning (PC) induced by a sub-lethal cerebral insult triggers brain tolerance against a subsequent severe injury through diverse mechanisms, including the modulation of the immune system. Tumor necrosis factor (TNF)-α-stimulated gene 6 (TSG-6), a hyaluronate (HA)-binding protein, has recently been involved in the regulation of the neuroimmune response following ischemic stroke. Thus, we aimed at assessing whether the neuroprotective effects of ischemic PC involve the modulation of TSG-6 in a murine model of transient middle cerebral artery occlusion (MCAo). The expression of TSG-6 was significantly elevated in the ischemic cortex of mice subjected to 1 h MCAo followed by 24 h reperfusion, while this effect was further potentiated (p < 0.05 vs. MCAo) by pre-exposure to ischemic PC (i.e., 15 min MCAo) 72 h before. By immunofluorescence analysis, we detected TSG-6 expression mainly in astrocytes and myeloid cells populating the lesioned cerebral cortex, with a more intense signal in tissue from mice pre-exposed to ischemic PC. By contrast, levels of TSG-6 were reduced after 24 h of reperfusion in plasma (p < 0.05 vs. SHAM), but were dramatically elevated when severe ischemia (1 h MCAo) was preceded by ischemic PC (p < 0.001 vs. MCAo) that also resulted in significant neuroprotection. In conclusion, our data demonstrate that neuroprotection exerted by ischemic PC is associated with the elevation of TSG-6 protein levels both in the brain and in plasma, further underscoring the beneficial effects of this endogenous modulator of the immune system.

Vertebrobasilar Artery Occlusion Treatment Outcomes Within 24 hours of Estimated Occlusion Time.

The aim of this study was to investigate the efficacy and safety of endovascular treatment (EVT) in patients with acute vertebrobasilar artery occlusion (VBAO) within 24 hours of estimated occlusion time (EOT) and to evaluate the effect of early and late time window in a cohort of patients with VBAO treated with EVT. Retrospective analysis was conducted on patients within 24 hours of the EOT in 65 stroke centers in China. Favorable outcome was defined as modified Rankin Scale ≤3 at 90 days. Patients were divided into the medical management (MM) group and the EVT group. Times were dichotomized into early (EOT ≤6 hours) and late (>6 hours) time windows. Multivariate logical regression models were used to evaluate the efficacy and safety of EVT and the effect of time windows on outcomes in EVT patients. Among 4124 patients, 2473 and 1651 patients were included in the early and late windows, respectively. 1702 patients received MM and 2422 were treated with EVT. EVT was associated with a higher rate of a favorable outcome at 90 days both in early (odds ratio [OR] 2.16, 95% CI 1.94-2.41) and late (OR 1.89, 95% CI 1.65-2.17) time windows. No differences were found regarding favorable outcome (OR 0.95, 95% CI 0.87-1.03) between VBAO patients treated with EVT within and beyond 6 hours. Patients with acute VBAO who received EVT within 24 hours were associated with improved favorable outcome compared with patients who received MM. EVT beyond 6 hours is feasible and safe with no increase in symptomatic intracranial hemorrhage.

Factors effecting the success of retrograde tibiopedal access and recanalization in infrapopliteal artery occlusions.

Peripheral arterial disease (PAD) is increasingly prevalent, particularly among the aging population. Retrograde tibiopedal access (RTPA) has emerged as a useful endovascular treatment for PAD. However, there is limited research examining factors that influence the efficacy of RTPA. To investigate factors affecting the access, crossing, and recanalization success rates of RTPA for infrapopliteal PAD treatment. A retrospective study was conducted on 720 patients who underwent endovascular treatment for PAD. Of these, 104 patients (mean age: 65.5 ± 16.2; 89 men) with 131 RTPA trials were included in the final evaluation. The disease and its duration, Rutherford score, smoking status, access site, and its occlusion status, access, crossing, and recanalization success were noted. Data were analyzed using Pearson's chi-square and Mann-Whitney U tests and multivariate logistic regression to evaluate the impact of various factors on success rates. The access success rate was 82.6%, the crossing success rate was 95.4%, and the recanalization success rate was 74%. Access success was significantly higher when the dorsal pedal artery (DPA) was the access artery compared with the posterior tibial artery (91.3% vs. 74.2%, P = 0.009). Access success was notably lower in patients with thromboangiitis obliterans compared with patients with diabetes mellitus (DM) and non-DM atherosclerosis (68.6% vs. 90.3% and 80.3%, P = 0.019). Recanalization success was higher when the puncture site was non-occluded (76.7% vs. 53.5%, P = 0.023). The study suggests that RTPA is a generally effective and safe technique for infrapopliteal PAD treatment. The most favorable outcomes are observed in individuals with DM who have a non-occluded DPA at the puncture site. Recanalization success is only affected by the patency of the artery at the puncture site. These findings offer targeted guidance for clinicians and highlight areas requiring further investigation.

Combining systems pharmacology, metabolomics, and transcriptomics to reveal the mechanism of Salvia miltiorrhiza-Cortex moutan herb pair for the treatment of ischemic stroke

Ischemic stroke (IS), predominantly triggered by blockages in cerebral blood flow, is increasingly recognized as a critical public health issue. The combination of Salvia miltiorrhiza (SM) and Cortex moutan (CM), traditional herbs in Eastern medicine, are frequently used for managing heart and brain vascular conditions. However, the exact mechanisms by which this herb pair (SC) combats IS remain largely unexplored. This investigation focuses on pinpointing the active constituents in SC that contribute to its protective role and deciphering the mechanisms countering cerebral ischemia, particularly in a middle cerebral artery occlusion (MCAO) rat model. We employed UPLC-Q-TOF-MS/MS alongside network pharmacology for predicting SC’s target actions against IS. Key ingredients were examined for their interaction with principal targets using molecular docking. The therapeutic impact was gauged through H&E, TUNEL, and Nissl staining, complemented by transcriptomic and metabolomic integration for mechanistic insights, with vital genes confirmed via western blot. UPLC-Q-TOF-MS/MS analysis revealed that the main components of SC included benzoylpaeoniflorin, salvianolic acid B, oxypaeoniflora, salvianolic acid A, and others. Network pharmacology analysis indicated that SC’s mechanism in treating IS primarily involves inflammation, angiogenesis, and cell apoptosis-related pathways, potentially through targets such as AKT1, TNF, PTGS2, MMP9, PIK3CA, and VEGFA. Molecular docking underscored strong affinities between these constituents and their targets. Our empirical studies indicated SC’s significant role in enhancing neuroprotection in IS, with transcriptomics suggesting the involvement of the VEGFA/PI3K/AKT pathway and metabolomics revealing improvements in various metabolic processes, including amino acids, glycerophospholipids, sphingomyelin, and fatty acids metabolisms.

Whether mTICI 3 or mTICI 2b is better in patients with vertebrobasilar artery occlusion undergoing endovascular treatment depends on pc-ASPECTS

BackgroundThe clinical relevance of differentiating between mTICI (modified Thrombolysis In Cerebral Infarction) 2b and mTICI 3 in patients with vertebrobasilar artery occlusion (VBAO) remains unclear. This study aimed to investigate...

Evaluation of collateral circulation in patients with internal carotid artery occlusion: A clinical and ultrasonographic multicenter study.

Internal carotid artery (ICA) occlusion is the major cause of ischemic stroke. The effect of collateral vessels on cerebral hemodynamics in ICA occlusion remains unclear. This study investigated the correlation between collateral vessels and the peak systolic velocity of the middle cerebral artery (MCA) in patients with ICA occlusion. The relevant collateral vessels included the anterior communicating (ACoA), posterior communicating (PCoA), and internal-external carotid (IECCA) arteries, respectively. Patients with unilateral ICA occlusion (n = 251) underwent transcranial Doppler imaging to detect the peak systolic velocity (PSV) of the MCA and other intracranial arteries. The clinical symptoms were assessed using the National Institutes of Health Stroke Scale (NIHSS). Patients with ACoA collaterals had significantly higher PSVMCA scores and significantly lower NIHSS scores than those without ACoA collaterals (p < 0.001). Patients without any notable collaterals and those with only IECCA had the lowest PSVMCA and highest NIHSS scores. The PSVMCA and NIHSS scores were negatively correlated (r = -0.566, p < 0.001). Collateral circulation patency in unilateral ICA occlusion was closely associated with clinical symptoms, and patients with ACoA collaterals may have favorable outcomes. (ClinicalTrials.gov Identifier: NCT02397655).

Combined treatment of wounded with traumatic aneurysm of posterior communicating artery complicated by intraventricular hemorrhage

Cerebral blood vessel trauma (CBVT) is a serious condition of craniocerebral injury. According to literature data, different varieties of CBVT in penetrating gunshot craniocerebral injuries are found in 30–45 % of cases. Traumatic pseudoaneurysms are the most common finding in late evaluation and can lead to life-threatening episodes of intracranial hemorrhage.In addition, CBVT includestraumatic occlusion, dissection of vessels, rupture of cerebral arteries, formation of arteriovenous fistulas (carotid-cavernous anastomoses), venous stasis, etc. Injured persons with traumatic dissection and injury of vertebrobasilar pool have the highest risks of lethal outcome. There are no largerandomised trials and national recommendations for the treatment of CBVT, individual observations and small series of clinical cases have been published. In this connection, there is a need for a detailed analysis of all clinical cases, the development of tactics for early diagnosis and an algorithm for the treatment of wounded with CBVT.The article presents a review of the literature data that characterizes the current understanding of CBVT, and a clinical case of traumatic occlusion of the middle cerebral artery and pseudoaneurysm of the posterior communicating artery in a wounded man with a gunshot penetrating cranioorbital wound, who was treated at the neurosurgical center of the N.N. Burdenko Main Military Clinical Hospital.In the early period after the injury, the patient underwent endovasal occlusion of a traumatic aneurysm of the posterior connective artery by microspirals followed by local thrombolysis of intraventricular hematomas through a ventricular catheter. The catamnesis was 150 days, the score on the modified Rankin scale was 3, the Glasgow outcome scale extended was 5.

A vascular endothelial growth factor-loaded chitosanhyaluronic acid hydrogel scaffold enhances the therapeutic effect of adipose-derived stem cells in the context of stroke.

Adipose-derived stem cell, one type of mesenchymal stem cells, is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery. However, its application has been limited by the complexities of the ischemic microenvironment. Hydrogel scaffolds, which are composed of hyaluronic acid and chitosan, exhibit excellent biocompatibility and biodegradability, making them promising candidates as cell carriers. Vascular endothelial growth factor is a crucial regulatory factor for stem cells. Both hyaluronic acid and chitosan have the potential to make the microenvironment more hospitable to transplanted stem cells, thereby enhancing the therapeutic effect of mesenchymal stem cell transplantation in the context of stroke. Here, we found that vascular endothelial growth factor significantly improved the activity and paracrine function of adipose-derived stem cells. Subsequently, we developed a chitosan-hyaluronic acid hydrogel scaffold that incorporated vascular endothelial growth factor and first injected the scaffold into an animal model of cerebral ischemia-reperfusion injury. When loaded with adipose-derived stem cells, this vascular endothelial growth factor-loaded scaffold markedly reduced neuronal apoptosis caused by oxygen-glucose deprivation/reoxygenation and substantially restored mitochondrial membrane potential and axon morphology. Further in vivo experiments revealed that this vascular endothelial growth factor-loaded hydrogel scaffold facilitated the transplantation of adipose-derived stem cells, leading to a reduction in infarct volume and neuronal apoptosis in a rat model of stroke induced by transient middle cerebral artery occlusion. It also helped maintain mitochondrial integrity and axonal morphology, greatly improving rat motor function and angiogenesis. Therefore, utilizing a hydrogel scaffold loaded with vascular endothelial growth factor as a stem cell delivery system can mitigate the adverse effects of ischemic microenvironment on transplanted stem cells and enhance the therapeutic effect of stem cells in the context of stroke.

Mesenteric ischemia caused by chronic occlusion of multiple mesenteric arteries: a case report

PurposeChronic mesenteric ischemia (CMI) is a rare disease that progresses with acute mesenteric ischemia, along with high mortality. How to choose the appropriate surgical method and the artery which should be opened first is the key to the treatment.Case reportIn this study, we successively used vascular bypass and endovascular therapy to treat a case of complex chronic mesenteric ischemia.ConclusionFor mesenteric ischemic disease, the superior mesenteric artery (SMA) should be opened preferentially. Arterial bypass or interventional therapy can be used, or both can be combined, to finally achieve the purpose of treatment.

Plasma Proteomics to Identify Drug Targets and Potential Drugs for Retinal Artery Occlusion: An Integrated Analysis in the UK Biobank.

Retinal artery occlusion (RAO), which is positively correlated with acute ischemic stroke (IS) and results in severe visual impairment, lacks effective intervention drugs. This study aims to perform integrated analysis using UK Biobank plasma proteome data of RAO and IS to identify potential targets and preventive drugs. A total of 7191 participants (22 RAO patients, 1457 IS patients, 8 individuals with both RAO and IS, and 5704 healthy age-gender-matched controls) were included in this study. Unique 1461 protein expression profiles of RAO, IS, and the combined data set, extracted from UK Biobank Plasma proteomics projects, were analyzed using both differential expression analysis and elastic network regression (Enet) methods to identify shared key proteins. Subsequent analyses, including single cell type expression assessment, pathway enrichment, and druggability analysis, were conducted for verifying shared key proteins and discovery of new drugs. Five proteins were found to be shared among the samples, with all of them showing upregulation. Notably, adhesion G-protein coupled receptor G1 (ADGRG1) exhibited high expression in glial cells of the brain and eye tissues. Gene set enrichment analysis revealed pathways associated with lipid metabolism and vascular regulation and inflammation. Druggability analysis unveiled 15 drug candidates targeting ADGRG1, which demonstrated protective effects against RAO, especially troglitazone (-8.5 kcal/mol). Our study identified novel risk proteins and therapeutic drugs associated with the rare disease RAO, providing valuable insights into potential intervention strategies.

Nattokinase's Neuroprotective Mechanisms in Ischemic Stroke: Targeting Inflammation, Oxidative Stress, and Coagulation.

Aims: Nattokinase (NK), a potent serine endopeptidase, has exhibited a variety of pharmacological effects, including thrombolysis, anti-inflammation, and antioxidative stress. Building on previous research highlighting NK's promise in nerve regeneration, our study investigated whether NK exerted protective effects in transient middle cerebral artery occlusion (tMCAO)-induced cerebral ischemia-reperfusion injury and the underlying mechanisms. Results: The rats were administered NK (5000, 10000, 20000 FU/kg, i.g., 7 days before surgery, once daily). We showed that NK treatment dose dependently reduced the infarction volume and improved neurological symptoms, decreased the proinflammatory and coagulation cytokines levels, and attenuated reactive oxygen species (ROS) in the infarcted area of tMCAO rats. We also found that NK could exert neuroprotective effects in a variety of vitro models, including the microglia inflammation model and neuronal oxygen-glucose deprivation/reperfusion (OGD/R) model. Notably, NK effectively countered OGD/R-induced neuron death, modulating diverse pathways, including autophagy, apoptosis, PARP-dependent death, and endoplasmic reticulum stress. Furthermore, the neuroprotection of NK was blocked by phenylmethylsulfonyl fluoride (PMSF), a serine endopeptidase inhibitor. We revealed that heat-inactive NK was unable to protect against tMCAO injury and other vitro models, suggesting NK attenuated ischemic injury by its enzymatic activity. We conducted a proteomic analysis and found inflammation and coagulation were involved in the occurrence of tMCAO model and in the therapeutic effect of NK. Innovation and Conclusion: In conclusion, these data demonstrated that NK had multifaceted neuroprotection in ischemic brain injury, and the therapeutic effect of NK was related with serine endopeptidase activity.

Inhibition of the AP-1/TFPI2 axis contributes to alleviating cerebral ischemia/reperfusion injury by improving blood-brain barrier integrity.

Reperfusion after cerebral ischemia leads to secondary damage to the nervous system, called cerebral ischemia/reperfusion injury (CIRI). The blood-brain barrier (BBB) consists of endothelial cells and tight junction (TJ) proteins, and its disruption aggravates CIRI. Two GSE datasets identified Tissue Factor Pathway Inhibitor 2 (TFPI2) as a differentially upregulated gene (Log2FC > 1, p < 0.01) in the cerebral cortex of ischemic rats, and TFPI2 affects angiogenesis of endothelial cells. Moreover, genes (c-Jun, c-Fos, FosL1) encoding subunits of Activator Protein-1 (AP-1), a transcription factor involved in IRI, were highly expressed in ischemic samples. Thus, the effects of the AP-1/TFPI2 axis on CIRI were explored. We determined increased TFPI2 expression in the cerebral cortex of rats receiving middle cerebral artery occlusion (MCAO) for 90min and reperfusion (R) for 48h. Then AAV2-shTFPI2 particles (5 × 1010 vg) were injected into the right lateral ventricle of rats 3weeks before MCAO/R. TFPI2 knockdown decreased infarct size and neuronal injury in ischemic rats. It improved BBB integrity, demonstrated by reduced FITC-dextran leakage in brain tissues of MCAO/R-operated rats. Furthermore, it increased the expression of TJ proteins (Occludin, Claudin-5, TJP-1) in the cerebral cortex of rats with CIRI. Consistently, we found that TFPI2 knockdown mitigated cell damage in mouse endothelial bEND.3 cells with oxygen and glucose deprivation (ODG) for 6h and reoxygenation (R) for 18h (OGD/R) treatment. High co-expression of c-Jun and c-Fos significantly elevated TFPI2 promoter activity. c-Jun knockdown inhibited TFPI2 expression in OGD/R-treated bEND.3 cell. Collectively, our findings demonstrate that inhibition of the AP-1/TFPI2 axis alleviates CIRI.

Acid sphingomyelinase inhibition induces cerebral angiogenesis post-ischemia/reperfusion in an oxidative stress-dependent way and promotes endothelial survival by regulating mitochondrial metabolism

Acid sphingomyelinase (ASM) inhibitors are widely used for the treatment of post-stroke depression. They promote neurological recovery in animal stroke models via neurorestorative effects. In a previous study, we found that antidepressants including amitriptyline, fluoxetine, and desipramine increase cerebral angiogenesis post-ischemia/reperfusion (I/R) in an ASM-dependent way. To elucidate the underlying mechanisms, we investigated the effects of the functional ASM inhibitor amitriptyline in two models of I/R injury, that is, in human cerebral microvascular endothelial hCMEC/D3 cells exposed to oxygen-glucose deprivation and in mice exposed to middle cerebral artery occlusion (MCAO). In addition to our earlier studies, we now show that amitriptyline increased mitochondrial reactive oxygen species (ROS) formation in hCMEC/D3 cells and increased ROS formation in the vascular compartment of MCAO mice. ROS formation was instrumental for amitriptyline’s angiogenic effects. ROS formation did not result in excessive endothelial injury. Instead, amitriptyline induced a profound metabolic reprogramming of endothelial cells that comprised reduced endothelial proliferation, reduced mitochondrial energy metabolism, reduced endoplasmic reticulum stress, increased autophagy/mitophagy, stimulation of antioxidant responses and inhibition of apoptotic cell death. Specifically, the antioxidant heme oxygenase-1, which was upregulated by amitriptyline, mediated amitriptyline’s angiogenic effects. Thus, heme oxygenase-1 knockdown severely compromised angiogenesis and abolished amitriptyline’s angiogenic responses. Our data demonstrate that ASM inhibition reregulates a complex network of metabolic and mitochondrial responses post-I/R that contribute to cerebral angiogenesis without compromising endothelial survival.

Ischemic Microenvironment-Targeted Bioinspired Lipoprotein Sequentially Penetrates Cerebral Ischemic Lesions to Rescue Ischemic Stroke.

Reperfusion injury represents a significant impediment to recovery after recanalization in an ischemic stroke and can be alleviated by neuroprotectants. However, inadequate drug delivery to ischemic lesions impairs the therapeutic effects of neuroprotectants. To address this issue, an ischemic microenvironment-targeted bioinspired lipoprotein system encapsulating lipoic acid (LA@PHDL) is herein designed to sequentially penetrate ischemic lesions and be readily taken up by neurons and microglia. In transient middle cerebral artery occlusion (tMCAO) mouse models, LA@PHDL accumulates rapidly and preferentially in the ischemic brain, with a 2.29-fold higher than the nontargeted nanoplatform in the early stage. Furthermore, LA@PHDL effectively restores neurological function, reduces infarct volume to 17.70%, prevents brain cell necrosis and apoptosis, and attenuates inflammation in tMCAO mouse models. This design presents new opportunities for delivering neuroprotectants to cerebral ischemic lesions to improve the outcome of an ischemic stroke.

Weisheng-tang protects against ischemic brain injury by modulating microglia activation through the P2Y12 receptor.

Background: Stroke, a leading cause of death and disability, lacks effective treatments. Post-stroke secondary damage worsens the brain microenvironment, further exacerbating brain injury. Microglia's role in responding to stroke-induced damage in peri-infarct regions is crucial. In this study, we explored Weisheng-tang's potential to enhance ischemic outcomes by targeting microglia. Methods: We induced middle cerebral artery occlusion and reperfusion in mice, followed by behavioral assessments and infarct volume analyses after 48h, and examined the changes in microglial morphology through skeleton analysis. Results: Weisheng-tang (300mg/kg) significantly reduced infarction volume and alleviated neurological and motor deficits. The number of activated microglia was markedly increased within the peri-infarct territory, which was significantly reversed by Weisheng-tang. Microglial morphology analysis revealed that microglial processes were retracted owing to ischemic damage but were restored in Weisheng-tang-treated mice. This restoration was accompanied by the expression of the purinergic P2Y12 receptor (P2Y12R), a key regulator of microglial process extension. Weisheng-tang increased neuronal Kv2.1 clusters while suppressing juxtaneuronal microglial activation. The P2Y12R inhibitor-ticagrelor-eliminated the tissue and functional recovery that had been observed with Weisheng-tang after ischemic damage. Discussion: Weisheng-tang improved experimental stroke outcomes by modulating microglial morphology through P2Y12R, shedding light on its neuroprotective potential in ischemic stroke.

Intervention effects of Naoxintong capsules on psychological and cardiac status in depressed rats after heart failure

Abstract Background Depression is a common clinical phenomenon in the patients with heart failure (HF). In traditional Chinese medicine (TCM), diseases in the brain and heart are thought to be correlated and interact. Naoxintong capsules (NXT) has been used for treating cardio-cerebrovascular diseases, while its therapeutic effect on depression after HF remains unclear. Objective The aim of the study is to evaluate the intervention effect of NXT on depression after HF. Methods Sprague-Dawley rats were assigned into the following 5 groups: sham, model, NXT (250, 1000 mg/kg), and valsartan (8 mg/kg). Coronary artery occlusion was performed to induce HF and subsequent depression in rats. The cardiac function was evaluated by echocardiography, hematoxylin-eosin staining, and Masson trichrome staining. The sucrose preference test and Morris water maze test were carried out to assess the depressive behaviors in rats. The ultrastructure of hippocampal CA1 neurons was observed and the levels of corticotropin-releasing hormone in the hypothalamus, brain-derived neurotrophic factor in the cortex, and adrenocorticotropic hormone (ACTH) in the plasma were determined by enzyme-linked immunosorbent assay. The levels of dopamine, 5-hydroxytryptamine, norepinephrine, and γ-aminobutyric acid in the hippocampus were measured by UPLC-QQQ-MS. Results NXT reduced myocardial injury and pathological changes in the cardiac tissue and increased the left ventricular ejection fraction, left ventricular fractional shortening, and cardiac output. NXT increased the sugar preference rate and number of crossings and shortened the escape latency. Furthermore, the NXT treatment restored the levels of corticotropin-releasing hormone, adrenocorticotropic hormone, brain-derived neurotrophic factor, dopamine, and γ-aminobutyric acid to the baseline values. Conclusions NXT not only demonstrates cardioprotective effect but also attenuates depression in the rats after HF. It may exert the antidepressant effect by inhibiting the hyperactivity of the hypothalamic-pituitary-adrenal axis and recovering the levels of neurotrophic factors and neurotransmitters.

Phenome-Wide Association of APOE Alleles in the All of Us Research Program.

Genetic variation in APOE is associated with altered lipid metabolism, as well as cardiovascular and neurodegenerative disease risk. However, prior studies are largely limited to European ancestry populations and differential risk by sex and ancestry has not been widely evaluated. We utilized a phenome-wide association study (PheWAS) approach to explore APOE-associated phenotypes in the All of Us Research Program. We determined APOE alleles for 181,880 All of Us participants with whole genome sequencing and electronic health record (EHR) data, representing seven gnomAD ancestry groups. We tested association of APOE variants, ordered based on Alzheimer's disease risk hierarchy (ε2/ε2<ε2/ε3<ε3/ε3<ε2/ε4<ε3/ε4<ε4/ε4), with 2,318 EHR-derived phenotypes. Bonferroni-adjusted analyses were performed overall, by ancestry, by sex, and with adjustment for social determinants of health (SDOH). In the overall cohort, PheWAS identified 17 significant associations, including an increased odds of hyperlipidemia (OR 1.15 [1.14-1.16] per APOE genotype group; P=1.8×10-129), dementia, and Alzheimer's disease (OR 1.55 [1.40-1.70]; P=5×10-19), and a reduced odds of fatty liver disease (OR 0.93 [0.90-0.95]; P=1.6×10-9) and chronic liver disease. ORs were similar after SDOH adjustment and by sex, except for an increased number of cardiovascular associations in males, and decreased odds of noninflammatory disorders of vulva and perineum in females (OR 0.89 [0.84-0.94]; P=1.1×10-5). Significant heterogeneity was observed for hyperlipidemia and mild cognitive impairment across ancestry. Unique associations by ancestry included transient retinal arterial occlusion in the European ancestry group, and first-degree atrioventricular block in the American Admixed/Latino ancestry group. We replicate extensive phenotypic associations with APOE alleles in a large, diverse cohort, despite limitations in accuracy for EHR-derived phenotypes. We provide a comprehensive catalog of APOE-associated phenotypes and present evidence of unique phenotypic associations by sex and ancestry, as well as heterogeneity in effect size across ancestry.

The level of inflammatory markers in patients with myocardial infarction after percutaneous coronary intervention

Cardiovascular diseases are among the most widespread diseases in the world that affect all ages and sometimes can lead to death. Atherosclerosis, coronary syndrome and myocardial infarction are usually associated with artery occlusion and require percutaneous coronary intervention (PCI) as a non-surgical procedure to restore blood flow to the heart. Inflammatory biomarkers, especially interleukins and cardiac biomarkers, have an important role in diagnosing the state of patients with heart damage. The goal of the study was to estimate the serum levels of interleukins and cardiac biomarkers after PCI to reduce the risk of acute coronary syndrome. The study included 100 persons between the ages of 40 and 69 diagnosed with acute coronary syndrome who had successful PCI and a control group consisting of 50 healthy participants of the same age. The levels of interleukins, сreatine kinase MB and myoglobin were measured using an enzyme-linked immunosorbent assay. Troponin and D-dimer levels were measured using immunoassay. It was found that patients before PCI had significantly higher levels of IL-1β, IL-6, IL-8, cardiac troponin I, D-dimer, creatine kinase-MB and myoglobin compared to the control group. One day after PCI, the levels of IL -6, IL-8, cardiac troponin I and D-dimer remained elevated. One week after PCI, the levels of IL-1β, IL-6, IL-8, CK-MB and myoglobin did not show significant differences compared to the control group, while the levels of cardiac troponin I and D-dimer remained higher. Results obtained indicate that in patients after PCI, the levels of interleukins decreased, indicating the reduction of inflammatory processes, but cardiac damage persists to a certain degree, even a week after PCI. Keywords: creatine kinase MB, D-dimer, interleukin, myocardial infarction, myoglobin, percutaneous coronary intervention