Asiatic acid alleviates vascular remodeling in BAPN-induced aortic dissection through inhibiting NF-κB p65/CX3CL1 signaling.

Inflammation assumes a pivotal role in the aortic remodeling of aortic dissection (AD). Asiatic acid (AA), a triterpene compound, is recognized for its strong anti-inflammatory properties. Yet, its effects on ß-aminopropionitrile (BAPN)-triggered AD have not been clearly established. The objective is to determine whether AA attenuates adverse aortic remodeling in BAPN-induced AD and clarify potential molecular mechanisms. In vitro studies, RAW264.7 cells pretreated with AA were challenged with lipopolysaccharide (LPS), and then the vascular smooth muscle cells (VSMCs)-macrophage coculture system was established to explore intercellular interactions. To induce AD, male C57BL/6J mice at three weeks of age were administered BAPN at a dosage of 1 g/kg/d for four weeks. To decipher the mechanism underlying the effects of AA, RNA sequencing analysis was conducted, with subsequent validation of these pathways through cellular experiments. AA exhibited significant suppression of M1 macrophage polarization. In the cell coculture system, AA facilitated the transformation of VSMCs into a contractile phenotype. In the mouse model of AD, AA strikingly prevented the BAPN-induced increases in inflammation cell infiltration and extracellular matrix degradation. Mechanistically, RNA sequencing analysis revealed a substantial upregulation of CX3CL1 expression in BAPN group but downregulation in AA-treated group. Additionally, it was observed that the upregulation of CX3CL1 negated the beneficial impact of AA on the polarization of macrophages and the phenotypic transformation of VSMCs. Crucially, our findings revealed that AA is capable of downregulating CX3CL1 expression, accomplishing this by obstructing the nuclear translocation of NF-κB p65. The findings indicate that AA holds promise as a prospective treatment for adverse aortic remodeling by suppressing the activity of NF-κB p65/CX3CL1 signaling pathway.

The impact of endovascular stents types on perioperative outcomes of ruptured abdominal aortic aneurysms: a single-center experience.

Introduction: Ruptured abdominal aortic aneurysm (rAAA) represents a critically urgent vascular surgical condition, and endovascular aneurysm repair (EVAR) is a clinically effective treatment option. This study aims to investigate whether the type of intravascular graft used for ruptured abdominal aortic aneurysms has an impact on perioperative outcomes of EVAR. Methods: A retrospective analysis was conducted on patients who underwent EVAR for ruptured abdominal aortic aneurysm at a single medical center from 2019 to 2022. Patients who required simultaneous stent implantation in the renal arteries or visceral arteries, as well as those with ruptured aneurysms located in the para-renal, supra-renal, or thoracoabdominal regions, were excluded from the analysis. Additionally, patients who underwent open surgery during the initial procedure or converted to open repair were excluded. The primary endpoint was perioperative mortality rate. Other study outcomes included perioperative complications, reoperation rates, and length of hospital stay. Characteristics and corresponding outcomes of patients receiving different endovascular stent treatments were compared using SPSS software. Results: A total of 58 patients received treatment with two types of endovascular stents: Gore Excluder (n = 29) and Microport Hercules (n = 29). The number of other endografts was too small for statistical analysis. Compared to patients treated with Hercules, those treated with Excluder had a significantly increased likelihood of concomitant coronary atherosclerosis (P = 0.009) and potentially higher creatinine levels (P = 0.014). Additionally, Excluder was more commonly used in patients with shorter aneurysm necks (P < 0.001). There was a statistically significant difference in overall mortality between the two groups (Hercules 27.6%, Excluder 6.9%, P = 0.037). Furthermore, patients who received Excluder treatment had lower mortality rates in subgroups of non-alcohol users (P = 0.028), non-diabetic patients (P = 0.027), and patients with dispersed thrombosis at the proximal neck (P = 0.046). In the multivariate analysis, the type of stent used (OR 0.06, 95% CI 0.00-1.31) and the occurrence of intraoperative complications (OR 20.70, 95% CI 1.14-76.70) in patients with rAAA was identified as an independent risk factor for perioperative mortality. Conclusion: Our study suggests that the management of intraoperative complications may be a modifiable factor that can improve outcomes. Patients receiving Excluder treatment demonstrated better performance in EVAR for single-center rAAA patients compared to other endovascular stents, and this difference warrants further investigation.

Nanomicrosphere sustained-release urokinase systems with antioxidant properties for deep vein thrombosis therapy.

Deep vein thrombosis (DVT) is a venous return disorder caused by abnormal clotting of blood in deep veins. After thrombosis, most of the thrombus will spread to the deep vein trunk throughout the limb. If DVT is not treated in time, most of them will develop into thrombosis sequelae and even threaten life. Intravenous thrombolytic drugs are the most promising strategy for treating DVT, but current drugs used for thrombolysis suffer from short half-lives and narrow therapeutic indexes. To effectively manage DVT, it is necessary to develop a novel multifunctional drug-loading system to effectively prolong the treatment time and improve the therapeutic efficacy. In this study, a urokinase-loaded protocatechuic aldehyde-modified chitosan microsphere drug-loading platform was constructed for the treatment of DVT. This microsphere adsorbed urokinase well through electrostatic interaction, and the introduction of bovine serum albumin conferred stability to the microspheres. Therefore, the microsphere drug delivery system could achieve slow drug release to effectively dissolve blood fibrin. In addition, chitosan grafted with protocatechuic aldehyde imparted excellent antioxidant activity to the system to reduce free radicals in the blood vessels. Effective management of oxidative stress could avoid abnormal platelet activation and new thrombus formation. The experimental results showed that this microsphere had good biocompatibility, anti-inflammatory properties, and considerable thrombolytic activity. In conclusion, this study provided a new direction and developed a novel multi-functional nano microsphere drug delivery platform for the treatment of DVT.

Brucella-infected abdominal aortic aneurysm: management strategies for an uncommon aneurysm.

Objective: The occurrence of Brucella-induced abdominal aortic aneurysms is an exceedingly rare phenomenon, yet it stands as one of the most severe complications within this context. The combined utilization of serological testing and imaging diagnostics has been validated as an effective approach for the identification of Brucella-induced abdominal aortic aneurysms. Presently, the predominant therapeutic strategies encompass antibiotic treatment and surgical intervention. Nonetheless, ongoing controversies persist concerning the establishment of diagnostic criteria, the optimal timing and selection of antibiotic regimens, and the nuanced decision between open surgical procedures and endovascular interventions. Through a meticulous analysis of cases originating from our institution as well as a comprehensive review of previously documented instances, we aim to engage in a detailed discourse on the salient diagnostic and therapeutic facets surrounding Brucella-induced abdominal aortic aneurysms. Methods: We conducted a retrospective summary of three cases involving Brucella-induced abdominal aortic aneurysms treated within our institution. Furthermore, we performed a comprehensive PubMed search, without imposing restrictions on language or publication year, to identify pertinent literature pertaining to Brucella-induced abdominal aortic aneurysms. The selection criteria primarily focused on case reports delineating occurrences of abdominal aortic aneurysms attributed to Brucella infection. Results: We present three distinct cases of Brucella-induced abdominal aortic aneurysms managed at our institution, providing comprehensive insights into the employed diagnostic and therapeutic approaches. Additionally, over the past five decades, a total of 24 cases in 23 publications of Brucella-induced abdominal aortic aneurysms have been reported on PubMed. The earliest report dates back to 1976. Conclusion: Our analysis suggests that Brucella-induced abdominal aortic aneurysm is characterized by a remarkably low incidence but is associated with a substantial risk of life-threatening complications. The integration of serological and imaging assessments assumes pivotal importance in facilitating prompt diagnosis of this condition. The prompt initiation of targeted antibiotic therapy is recommended, and the selection of appropriate surgical strategies should be guided by considerations including aneurysm dimensions and morphological attributes. The timely identification and intervention carry utmost significance in retarding disease advancement and ameliorating unfavorable clinical outcomes.

Quadruple fenestration aortic stent implantation combined with unilateral IBE and internal iliac artery stent implantation for complex abdominal aortic aneurysm: one case report.

An abdominal aortic aneurysm is a frequently encountered clinical condition, which necessitates prompt and effective remediation to avoid rupture. Surgeons must meticulously select an appropriate method of repair and assess the long-term surgical prognosis when dealing with patients with complex abdominal aortic aneurysms. In this case report, a 74-year-old man was hospitalized due to acute abdominal pain. Upon further examination, it was discovered that he was suffering from a complex abdominal aortic aneurysm. The thoracoabdominal aorta CTA showed that the aneurysm involved both renal arteries, the part below the kidney was severely twisted, the neck of the aneurysm was short, and it was accompanied by bilateral common iliac and internal iliac aneurysms, and there were considerable thrombus attached to the vessel wall. In this case, our team used 3D technology to simulate the spatial structure of the aneurysm and comprehensively evaluate the patient's condition. Ultimately, we decided to perform a quadruple fenestration aortic stent implantation and endovascular repair of aortic aneurysm, combined with right IBE and internal iliac artery stent implantation, right internal iliac artery reconstruction, and left internal iliac artery aneurysm embolization on this patient. This is an innovative surgical method. The operation was successful and the patient recovered well after the operation.

The predictive value of nontraditional lipid parameters for intracranial and extracranial atherosclerotic stenosis: a hospital-based observational study in China.

BACKGROUND: Ischemic strokes are primarily caused by intracranial and extracranial atherosclerotic stenosis. Nontraditional lipid parameters broaden traditional lipid profiles, better reflect the metabolism and interaction between different lipid components, and optimize the predictive ability of lipid profiles for atherosclerotic diseases. This research was carried out to investigate the predictive value of nontraditional lipid parameters for intracranial or extracranial atherosclerotic stenosis. METHODS: The investigation collected data from inpatients who underwent cervical vascular ultrasonography, carotid CTA, cerebral artery CTA or MRA, and brain MRI or CT from December 2014 to December 2021. The nontraditional lipid parameters were calculated by collecting traditional lipid parameters. To evaluate the predictive power of nontraditional lipid parameters, logistic regression and receiver operating characteristic curve (ROC) analyses were performed. RESULTS: Based on the inclusion and exclusion criteria, 545 patients were included. According to the imaging results, inpatients were divided into two groups, including no intracranial or extracranial atherosclerotic stenosis (n = 250) and intracranial or extracranial atherosclerotic stenosis (AS, n = 295). Among them, AS was further divided into three subgroups: intracranial atherosclerotic stenosis (ICAS), extracranial atherosclerotic stenosis (ECAS) and combined intracranial and extracranial atherosclerotic stenosis (IECAS). Logistic regression analysis showed that nontraditional lipid parameters, including the atherogenic index of plasma (AIP), TG/HDL-C, remnant cholesterol (RC), nonhigh-density lipoprotein cholesterol (non-HDL-C), lipoprotein combine index (LCI), atherogenic coefficient (AC), Castelli's index-I (CRI-I) and Castelli's index-II (CRI-II), were significantly correlated with intracranial or extracranial atherosclerotic stenosis (P < 0.05). Compared with other nontraditional lipid parameters, regardless of adjusting for potential confounding factors, AIP had a greater OR value in ICAS (OR = 4.226, 95% CI: 1.681-10.625), ECAS (OR = 2.993, 95% CI: 1.119-8.003) and IECAS (OR = 4.502, 95% CI: 1.613-12.561). ROC curve analysis revealed that nontraditional lipid parameters had good predictive power for intracranial or extracranial atherosclerotic stenosis. CONCLUSIONS: This Chinese hospital-based study demonstrates that nontraditional lipid parameters (AIP, LCI, RC, CRI-II, AC, CRI-I and non-HDL-C) are effective predictors of intracranial and extracranial atherosclerotic stenosis, of which AIP may be a significant risk factor for predicting atherosclerotic arterial stenosis in the intracranial or extracranial regions.

Management of an Isolated Left Vertebral Artery on the Arch During Zone 2 Landing Thoracic Endovascular Aortic Repair: A Multicentre Retrospective Study.

OBJECTIVE: To compare the early and midterm outcomes of three different strategies for an isolated left vertebral artery on the arch (LVoA) revascularisation during thoracic endovascular aortic repair (TEVAR) with a proximal zone 2 landing. METHODS: Between January 2016 and December 2021, 67 patients with LVoA and aortic arch pathologies who underwent zone 2 landing TEVAR at four medical centres were enrolled. These patients were divided into three groups for comparison: the novel chimney (group A, n = 28) with the right brachial-left brachial through and through (RLT) procedure; in vitro fenestration (group B, n = 24); and transposition (group C, n = 15). The flow direction and velocity of the LVoA was examined by Doppler ultrasound in the pre-, intra-, and post-operative periods. Primary outcomes were all cause mortality and new neurological symptoms. RESULTS: No deaths or new neurological symptoms occurred within 30 days. Early type Ia endoleak rates were 18% (n = 5), 17% (n = 4), and 0% in groups A, B, and C, respectively (p = .22). All patients had antegrade flow of the LVoA. The mean ± standard deviation duration of follow up was 63.6 ± 4.0 months. No deaths were observed during follow up. The rates of new neurological symptoms were 0%, 8%, and 33% in groups A, B, and C, respectively. The rates of midterm type Ia endoleak were 7%, 12%, and 0% in groups A, B, and C, respectively (p = .35). Bidirectional flow rates in the LVoA were 0%, 21%, and 27% in groups A, B, and C, respectively (p = .021). Two (8%) and three (20%) patients in groups B and C underwent a secondary procedure because of mild dizziness, but this was not necessary in group A (p = .058). CONCLUSION: The novel chimney technique of the RLT procedure may be feasible for patients with a LVoA requiring zone 2 anchoring. Accurate determination of the safety and feasibility of this novel technique requires larger sample sizes and longer follow up.

Single-branched stent-graft with on-table fenestration for endovascular repair of primary retrograde type A aortic dissection: A multicenter retrospective study.

Objective: This study aims to evaluate the feasibility, efficacy, and safety of a single-branched stent-graft with on-table fenestration for primary retrograde type A aortic dissection (RTAD) during thoracic endovascular aortic repair (TEVAR). Materials and methods: From January 2019 to December 2021, 36 patients with primary RTAD from five tertiary hospitals received medical management in the acute phase. They underwent TEVAR with a proximal zone 1 landing for aortic arch reconstruction in the subacute phase, using a fenestration technique on a single-branched stent-graft. Nearly 2 weeks after admission, computed tomography angiography (CTA) was re-examined to evaluate the thrombosis status of retrograde false lumen (FL). The primary outcomes were technical success, patency of the target branch arteries, and absence of type Ia endoleaks. The second outcomes were stent-graft-related complications and all-cause mortality. Results: The mean age was 56.2 ± 11.3 years, and 29 (80.6%) were male. After a median interval of 18.0 [interquartile range (IQR), 17.0-20.3] days of medical treatment, the partial and complete thrombosis of proximal FL rates increased to 52.8% and 47.2%, respectively. One patient (2.8%) experienced postoperative type Ia endoleaks, and was successfully re-treated using coli and Onyx glue. The median hospital stay was 20.5 (IQR, 18.0-23.0) days. The overall technical success rate was 100%. The median follow-up time was 31.5 (IQR, 29.8-34.0) months. There was one death (2.8%) due to gastrointestinal bleeding. Distal aortic segmental enlargement (DASE) occurred in two (5.6%) patients. No major complications or recurrent dissections in the proximal landing zone were recorded during follow up. Conclusion: The retrograde FL in primary RTAD could realize partial or complete thrombosis after medical management in the acute phase, and it might be regarded as a valid proximal landing zone for endovascular repair. The single-branched stent graft with on-table fenestration performed in the subacute phase may be feasible strategy in selective primary RTAD patients.

A systemic review and meta-analysis comparing the ability of diagnostic of the third heart sound and left ventricular ejection fraction in heart failure.

Objective: This study aimed to compare the sensitivity and specificity of diagnosis between the third heart sound (S3) and left ventricular ejection fraction (LVEF) in heart failure (HF). Methods: Relevant studies were searched in PubMed, SinoMed, China National Knowledge Infrastructure, and the Cochrane Trial Register until February 20, 2022. The sensitivity, specificity, likelihood ratio (LR), and diagnostic odds ratio (DOR) were pooled. The symmetric receiver operator characteristic curve (SROC) and Fagan's nomogram were drawn. The source of heterogeneity was explored by meta-regression and subgroup analysis. Results: A total of 19 studies, involving 5,614 participants, were included. The combined sensitivity of S3 was 0.23 [95% confidence interval (CI) (0.15-0.33), specificity was 0.94 [95% CI (0.82-0.98)], area under the SROC curve was 0.49, and the DOR was 4.55; while the sensitivity of LVEF was 0.70 [95% CI (0.53-0.83)], specificity was 0.79 [95% CI (0.75-0.82)], area under the SROC curve was 0.79, and the DOR was 8.64. No publication bias was detected in Deeks' funnel plot. The prospective design, partial verification bias, and blind contributed to the heterogeneity in specificity, while adequate description of study participants contributed to the heterogeneity in sensitivity. In Fagan's nomogram, the post-test probability was 48% when the pre-test probability was set as 20%, while in LVEF, the post-test probability was 45% when the pre-test probability was set as 20%. Conclusion: The use of S3 alone presented lower sensitivity in diagnosing HF compared with LVEF, whereas it was useful in early pathological assessment.

Alpha-ketoglutarate ameliorates abdominal aortic aneurysm via inhibiting PXDN/HOCL/ERK signaling pathways.

Abdominal aortic aneurysm (AAA) represents the serious vascular degenerative disorder, which causes high incidence and mortality. Alpha-ketoglutarate (AKG), a crucial metabolite in the tricarboxylic acid (TCA) cycle, has been reported to exert significant actions on the oxidative stress and inflammation. However, its role in AAA still remains elusive. Herein, we examined the effects of AKG on the formation of AAA. The study established an elastase-induced mouse abdominal aortic aneurysms model as well as a TNF-α-mediated vascular smooth muscle cells (VSMCs) model, respectively. We displayed that AKG pre-treatment remarkably prevented aneurysmal dilation assessed by diameter and volume and reduced aortic rupture. In addition, it was also observed that AKG treatment suppressed the development of AAA by attenuating the macrophage infiltration, elastin degradation and collagen fibers remodeling. In vitro, AKG potently decreased TNF-α-induced inflammatory cytokines overproduction, more apoptotic cells and excessive superoxide. Mechanistically, we discovered that upregulation of vpo1 in AAA was significantly suppressed by AKG treatment. By exploring the RNA-seq data, we found that AKG ameliorates AAA mostly though inhibiting oxidative stress and the inflammatory response. PXDN overexpression neutralized the inhibitory effects of AKG on ROS generation and inflammatory reaction in MOVAS. Furthermore, AKG treatment suppressed the expression of p-ERK1/2, 3-Cl Tyr in vivo and in vitro. ERK activator disrupted the protective of AKG on TNF-α-induced VSMCs phenotypic switch. Conclusively, AKG can serve as a beneficial therapy for AAA through regulating PXDN/HOCL/ERK signaling pathways.

Oncostatin M promotes the ox-LDL-induced activation of NLRP3 inflammasomes via the NF-κB pathway in THP-1 macrophages and promotes the progression of atherosclerosis.

Background: Oncostatin M (OSM) is reported to be involved in many stages of atherosclerosis, including endothelial dysfunction, chronic inflammation, and smooth muscle cell migration. This study explored the effects of OSM on foam cell formation and its corresponding molecular mechanisms. Methods: THP-1 cells were treated with phorbol-12-myristate-13-acetate (PMA) to induce macrophage differentiation and were then exposed to oxidized low-density lipoprotein (ox-LDL). OSM expression was analyzed by quantitative reverse transcription-polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay (ELISA). OSM-specific small interfering RNAs (siRNAs) were transfected into THP-1 macrophages. The effects of OSM silencing were evaluated by Oil Red O staining, ELISA, and Western blotting. Moreover, the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasomes was detected by western blotting and immunofluorescence. Results: OSM was highly expressed in THP-1 macrophages in a time- and dose-dependent fashion. Silencing OSM significantly reduced the total cholesterol content and Oil Red O staining levels in ox-LDL-treated macrophages. Silencing OSM significantly inhibited ox-LDL-induced cytokine release, including TNF-α, IL-1ß, IL-6, and IL-18. Ox-LDL activated p65 and NLRP3, which further induced caspase-1 cleavage, apoptosis-associated, speck-like protein containing a caspase-1 recruitment domain (ASC) upregulation, and gasdermin-D (GSDMD)-N fragmentation. Overexpression of NLRP3 significantly reversed the effects of OSM silencing on ox-LDL-induced foam cell formation and inflammation. Conclusions: OSM was highly expressed in the cell model of atherosclerosis. OSM has a promoting role in ox-LDL-induced foam cell formation and inflammation via the activation of p65-NLRP3 signaling pathways. Silencing OSM may be has benefit in treating atherosclerosis.

Efficacy and safety of drug-coated balloon versus non-drug-coated balloon combined with bare metal stent implantation in treatment of patients with occlusions of the superficial femoral artery: a retrospective study in clinical practice.

OBJECTIVE: To assess the efficacy and safety of drug-coated balloon and non-drug-coated balloon combined with bare metal stent implantation for the treatment of patients with occlusions of the superficial femoral artery. METHODS: In this retrospective study, 83 patients with occlusions of the superficial femoral artery were included. Among them, 41 patients received paclitaxel drug coated balloon treatment combined with bare metal stent implantation treatment (experimental group), the remaining 42 received non-drug-coated balloon treatment (control group). Patients were followed up at 1, 6, and 12 months after surgery. The primary clinical assessments, including ankle brachial index (ABI), RutherFord grade, Doppler ultrasound, or CT angiography (CTA), were used to observe the patency of target vessels, perioperative and postoperative complications. RESULTS: All the diseased vessels were successfully opened. There were no serious intraoperative complications such as vascular rupture or acute thrombosis. There was no significant difference in ankle brachial index, RutherFord grade, and total score between the two groups at one month and six months after operation (P>0.05). There was no significant difference in mortality, amputation rate, or thrombosis between the two groups (P>0.05). Twelve months after the operation, the ankle brachial index, Rutherford grade and total score of the experimental group were better than those of the control group (P<0.05). There was no significant difference in mortality, amputation rate, or thrombosis between the two groups (P>0.05). CONCLUSION: Paclitaxel coated balloon is safe and effective in the treatment of superficial femoral arteriosclerosis occlusion. It can significantly improve the ABI and Rutherford grades of patients, and it had a higher patency rate and lower reconstruction rate, but it may affect the healing ability of foot ulcer.

Extended Stent Coverage Decreases Distal Aortic Segmental Enlargement After the Endovascular Repair of Acute Complicated Type B Aortic Dissection: A Multi-Center Retrospective Study of 814 Patients.

PURPOSE: This study aimed to investigate the effect of distal aortic segmental enlargement (DASE) after thoracic endovascular aortic repair for complicated type B aortic dissection (cTBAD). MATERIALS AND METHODS: From March 2003 to October 2018, 814 patients with acute cTBAD from 5 medical centers were retrospectively identified. DASE is indicated as the enlargement of distal aortic segmental volume ≥1.6 fold of the preoperative volume compared with the most recent postoperative computed tomography angiography (CTA) scan. Of these patients, 635 (78%) were identified as non-DASE, and 179 (22%) were identified as DASE. Competing risk analysis was performed to compare late death and distal aortic reintervention between the groups. The morphological variables and false lumen thrombosis at 7 aortic levels were measured based on the preoperative CTA and the most recent CTA. Univariate and multivariate Cox regression analyses were used to assess the independent predictors of DASE. RESULTS: The mean follow-up time of the entire cohort was 5.6 years (interquartile range: 2.4-8.3 years). There were total of 208 late deaths, including 94 (14.8%) deaths in non-DASE group versus 114 (63.7%) deaths in the DASE group. Distal aortic reintervention was observed in 89 patients, with 43(6.7%) in the non-DASE group versus 46 (25.7%) in the DASE group. The cumulative incidence of late death and distal aortic reintervention were significantly higher in the DASE than in the non-DASE group (p<0.001). In morphological analysis, significant incomplete false lumen thrombosis was observed in all distal aortic segments above the aortic level of celiac artery (p<0.01). According to multivariate analysis, the Marfan syndrome, stent coverage to the level of diaphragm and the level of celiac artery were independent predictors of the DASE (p<0.001). Patients with extended stent coverage to the level of celiac artery have shown a lower incidence of DASE (p<0.010). CONCLUSION: Compared with the non-DASE group, patients with DASE demonstrated a higher rate of late death and distal aortic reintervention. For the cTBAD population, extended stent-graft coverage to the aortic section between diaphragm and celiac artery might serve as a "cost-efficient" cutoff point aiming to reduce the risk of DASE.

Ultrasonic Imaging of Carotid Inflammatory Plaque with Superparamagnetic Nanoparticles.

Chronic inflammation can stimulate the formation and progression of atherosclerotic plaques and increase the vulnerability of plaques. However, there are few studies on the changes of carotid inflammatory plaques during treatment. Our study attempted to investigate the use of superparamagnetic iron oxide nanoparticle (SPION) ultrasound imaging to detect the expression of vascular cell adhesion molecule-1 (VCAM-1) in patients with carotid plaques and analyze the effects of SPION ultrasound imaging in inflammatory plaque visualization effect. SPION microbubble contrast agents have good imaging effects both in vivo and in vitro. We conjugated the VCAM-1 protein to the microbubbles wrapped in SPIONs to form SPIONs carrying VCAM-1 antibodies. Observe the signal intensity of SPIONs carrying VCAM-1 antibody to arteritis plaque. The results showed that the SPION contrast agent carrying VCAM-1 antibody had higher peak gray-scale video intensity than the other two groups of contrast agents not carrying VCAM-1 antibody. It shows that SPIONs have excellent imaging effects in ultrasound imaging, can evaluate the inflammatory response of arterial plaque lesions, and are of great significance for the study of carotid inflammatory plaque changes.

Anti-Atherosclerotic Effect of Afrocyclamin A against Vascular Smooth Muscle Cells Is Mediated via p38 MAPK Signaling Pathway.

This article published in Cell J (Yakhteh), Vol 23, No 2, 2021, on pages 191-198, corresponding author and corresponding address were changed based on authors' request. The authors would like to apologies for any inconvenience caused.

Anti-Atherosclerotic Effect of Afrocyclamin A against Vascular Smooth Muscle Cells Is Mediated via p38 MAPK Signaling Pathway.

OBJECTIVE: Research suggests that fine particulate matter (PM2.5) contributes to the expansion and development of atherosclerosis. Infiltration and proliferation of vascular smooth muscle cells (VSMCs) from the blood vessel media into the intima, is an important step in the atherosclerosis pathophysiology. Afrocyclamin A, is an oleanane-type triterpene saponin, isolated from Androsace umbellate, which is commonly used in Chinese herbal medicine. In the study, we examined the effect of Afrocyclamin A on PM2.5-induced VSMCs proliferation and scrutinized possible mechanisms of action. MATERIALS AND METHODS: In the experimental study, counting Kit-8 (CCK-8) assay was used for estimation of VSMCs viability. BrdU immunofluorescence was used for estimation of VSMCs proliferation. The levels of antioxidant parameters such as malonaldehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH); proinflammatory cytokines such as interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), nitric oxide (NO), endothelin-1 (ET-1), and vascular cell adhesion molecule-1 (VCAM-1), were estimated. The expression of proliferating cell nuclear antigen (PCNA) and phospho-p38 MAPK (p-p38 MAPK) was assessed. RESULTS: Compared to PM2.5-treated cells, in addition to reducing PM2.5-induced VSMCs proliferation, Afrocyclamin A reduced the expression of PCNA and p-p38 MAPK, down-regulated the level of TNF-α, IL-1ß, IL-6, VCAM-1, MDA and ET-1, and up-regulated SOD, GSH and NO level. Furthermore, the anti-proliferative effect of Afrocyclamin A was considerably increased following co-incubation of Afrocyclamin A with SB203580 (p38 MAPK inhibitor) in comparison with Afrocyclamin A-treated cells. CONCLUSION: Based on the results, we can conclude that Afrocyclamin A might reduce PM2.5-induced VSMCs proliferation via reduction of p38 MAPK signaling pathway.

A Systematic Review and Meta-Analysis Comparing FAST and BEFAST in Acute Stroke Patients.

OBJECTIVE: To evaluate and compare the predictive value of Face, Arm, Speech Test (FAST) and Balance, Eyes, Face, Arm, Speech, Time (BEFAST) scale in the acute ischemic stroke (AIS). METHODS: We searched Medline and Ovid databases for relevant literature in the English language. There were no limitations on the date. The sensitivity, specificity, likelihood ratio, and diagnostic odds ratio were pooled for meta-analysis. The symmetric receiver operator characteristic curve and Fagan's Nomogram were drawn, and meta-regression and subgroup analysis were used to explore the source of heterogeneity. RESULTS: A total of 9 studies, including 6,151 participants, were analyzed. The combined sensitivity of FAST was 0.77 [95% CI (0.64-0.86)], specificity was 0.60 [95% CI (0.38-0.78)], the area under the ROC curve was 0.76, and the diagnostic ratio was 1.57, while the sensitivity of BEFAST was 0.68 [95% CI (0.23-0.93)], specificity was 0.85 [95% CI (0.72-0.92)], the area under the ROC curve was 0.86, and the diagnostic odds ratio was 2.44. No publication bias was detected in Deeks' funnel plot. For FAST, meta-regression analysis showed that the prospective design, satisfactory description of the index test, and a broad spectrum of disease contributed to the heterogeneity in sensitivity, while no sources contributed to the heterogeneity in sensitivity. When the pretest probability was set as 20%, the posterior probability in Fagan's Nomogram was 32%; however, when the pretest probability was set as 20% in BEFAST, the posterior probability in Fagan's Nomogram was 52%. CONCLUSIONS: Our findings indicated that FAST and BEFAST might be useful in the diagnosis of acute ischemic stroke. The diagnostic value of BEFAST in acute ischemic stroke was higher than in FAST; thus, it might have an important role in the fast recognition of acute ischemic stroke.

Lycopene Alleviates Hepatic Hypoxia/Reoxygenation Injury Through Nrf2/HO-1 Pathway in AML12 Cell.

[Figure: see text] Lycopene (lyc) has an effect on preventing cancer, yet its effects on hypoxia/reoxygenation (H/R) injury remained obscure. The study aimed at discovering its role in preventing hepatic cells against H/R injury. Hepatic cells were incubated in hypoxia incubator to simulate ischemia/reperfusion injury in vitro. Cell viability was detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after Lycopene treatment with or without ML385 (nuclear factor erythroid 2-related factor 2 [Nrf2] inhibitor). Lactate dehydrogenase (LDH) and malondialdehyde (MDA) content were detected. Cellular cytokine (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA). Hepatic cell apoptosis and cellular reactive oxygen species (ROS) content was detected by flow cytometry. Nrf2 transfer was observed using immunofluorescence staining. Nrf2 and heme oxygenase-1 (HO-1) expressions were detected with quantitative real-time polymerase chain reaction and western blot as needed. In hepatic cells, after H/R, the viability was dropped, TNF-α and IL-6 levels and LDH and MDA content were increased, with high apoptosis rate and ROS content. Lycopene led to a reversed effect, with promotion on Nrf2 transfer from cytoplasm into nucleus and Nrf2/HO-1 pathway activation. Further experiments showed that ML385 could reverse the effects of Lycopene. Lycopene could activate Nrf2/HO-1 pathway to protect hepatic cells against H/R injury.

Toxoplasma gondii infection in patients with lung diseases in Shandong province, eastern China.

Toxoplasma gondii, an intracellular protozoan parasite, can induce various clinical symptoms. T. gondii has been considered to play an important role in the pathogenesis of lung diseases. This survey was conducted to explore the correlation between T. gondii infection and lung diseases through a case-control study carried out in Shandong province, eastern China. In the present survey, T. gondii IgG antibodies were found in 76/398 (19.10%) of patients with lung diseases, which was significantly higher (P < 0.001) than the level found in the control subjects (35/398; 8.79%) through serological diagnosis. Patients with lung cancer have the highest T. gondii seroprevalence (26.19%), followed by Pulmonary cyst (25.00%), Tuberculosis (17.07%), Pneumonia (16.33%) and chronic obstructive pulmonary disease (COPD) (16.05%). Moreover, a semi-nest PCR targeted T. gondii B1 gene was employed to detect the T. gondii DNA in the blood samples. T. gondii DNA was detected in 5.53% blood samples of patients with lung diseases and 2.51% control subjects, respectively. The present study firstly shows that T. gondii has a high probability to infect the patients with lung diseases. Thus, the potential presence of T. gondii in patients with lung diseases should be appreciated during in the course of treatment and safeguard procedures should be implemented to protect vulnerable patients with lung diseases.

Integrative transcriptomic and proteomic analysis reveals CD9/ITGA4/PI3K-Akt axis mediates trabecular meshwork cell apoptosis in human glaucoma.

Glaucoma has been the leading cause of irreversible blindness worldwide. High intraocular pressure (IOP) is a high-risk factor of glaucoma, repression of which has been the important treatment of glaucoma in clinic. Trabecular meshwork is crucial for maintaining IOP in aqueous humour out-flow system. It is urgent to reveal the molecular mechanism of trabecular meshwork in glaucoma. Previous studies found that some pathways were related to glaucoma, such as extracellular matrix (ECM)-receptor interaction, phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) and apoptosis. To identify novel molecules in glaucoma, we performed high-throughput transcriptome and proteome analysis to immortal human trabecular meshwork cells (iHTM) and glaucomatous human trabecular meshwork cells (GTM3 ), respectively. Twenty-six up-regulated genes/proteins and 59 down-regulated genes/proteins were identified as the high-risk factors based on differential analysis, including some known factors of glaucoma. Furthermore, a glaucoma-related protein-protein interaction (PPI) network was constructed for investigating the function roles of risk factors. Some genes were identified as potential regulator in the pathogenesis of glaucoma based on the topology analysis and module analysis to the network. Importantly, we identified and demonstrated that CD9 played key roles in glaucoma by biological experiment. CD9 is down-regulated in glaucoma, overexpression of CD9 can active integrin α4 (ITGA4), PI3K and Akt, which lead to the decreased apoptosis and attenuate glaucoma. All these results provide a novel molecular therapy of glaucoma.