Treatment Strategy for Splenic Artery Aneurysms and Novel Classification Based on Imaging.

OBJECTIVE: The incidence of splenic artery aneurysms (SAAs) has increased with advancements in imaging techniques, necessitating a comprehensive classification to guide treatment strategies. This study aims to propose a novel classification system for SAAs based on aneurysm characteristics and to review treatment outcomes at our center. METHODS: This retrospective study included 113 SAAs patients admitted at Peking Union Medical College Hospital from January 2019 to December 2023, assessed using computed tomography angiography (CTA) or digital subtraction angiography (DSA). A new classification system was devised based on the aneurysms' location, morphology, integrity, and parent artery anatomy. Treatment strategies were determined based on these characteristics, with interventions ranging from endovascular therapy to laparoscopic and open surgery. Patients were followed up post-intervention to assess mortality, complications, reinterventions, and aneurysm-related outcomes. RESULTS: The study cohort of 113 patients with 127 SAAs had a predominance of female patients (63.7%) and a mean age of 52.7 years. The SAAs were classified into five types, with Type I being the most common. The intervention techniques varied across types, with sac embolization, covered stent implantation, and artery embolization being the most frequently employed. The overall technical success rate was 94.7%, with perioperative complication and reintervention rates of 25% and 0.9%, respectively, and no deaths within 30 days post-intervention. The median follow-up duration was 21 months, with overall complications rate of 3.5% and no aneurysm-related complications or deaths. CONCLUSIONS: The proposed classification system effectively guides the selection of treatment strategies for SAAs, incorporating key anatomical and morphological features. This system facilitated high technical success and low complication rates, underscoring the importance of tailored techniques in managing SAAs. Further research is necessary to validate this classification system and optimize treatment algorithms.

Characterization of the proteome of stable and unstable carotid atherosclerotic plaques using data-independent acquisition mass spectrometry.

BACKGROUND: Currently, noninvasive imaging techniques and circulating biomarkers are still insufficient to accurately assess carotid plaque stability, and an in-depth understanding of the molecular mechanisms that contribute to plaque instability is still lacking. METHODS: We established a clinical study cohort containing 182 patients with carotid artery stenosis. After screening, 39 stable and 49 unstable plaques were included in the discovery group, and quantitative proteomics analysis based on data independent acquisition was performed for these plaque samples. Additionally, 35 plaques were included in the validation group to validate the proteomics results by immunohistochemistry analysis. RESULTS: A total of 397 differentially expressed proteins were identified in stable and unstable plaques. These proteins are primarily involved in ferroptosis and lipid metabolism-related functions and pathways. Plaque validation results showed that ferroptosis- and lipid metabolism-related proteins had different expression trends in stable plaques versus unstable fibrous cap regions and lipid core regions. Ferroptosis- and lipid metabolism-related mechanisms in plaque stability were discussed. CONCLUSIONS: Our results may provide a valuable strategy for revealing the mechanisms affecting plaque stability and will facilitate the discovery of specific biomarkers to broaden the therapeutic scope.

Exosomes From IgE-Stimulated Mast Cells Aggravate Asthma-Mediated Atherosclerosis Through circRNA CDR1as-Mediated Endothelial Cell Dysfunction in Mice.

BACKGROUND: IgE has been known for mediating endothelial cell dysfunction and mast cell (MC) activation to fuel asthma-aggravated high-fat diet-induced atherosclerosis. However, it remains unclear for the mechanism of asthma-mediated atherosclerosis, especially the potential involvement of IgE in the exacerbation of asthma-mediated atherosclerosis with a standard laboratory diet, and the cross talk between endothelial cells and MCs. METHODS: Asthma-mediated atherosclerosis mice models under a standard laboratory diet and FcεR1 knock-out mice were used to determine the role of IgE-FcεR1 signaling in asthma-mediated atherosclerosis, which was assessed by Oil Red O staining and immunohistochemistry. Various in vitro assays including nanoparticle tracking analysis and transmission electron microscopy were used to evaluate exosome characteristics. Immunofluorescence and fluorescent in situ hybridization approaches were used to evaluate the effect and mechanism of MC-secreted exosomes encapsulated circular RNA CDR1as (cerebellar degeneration-related 1 antisense) on endothelial cells in vivo and in vitro. Finally, cohort studies examined the plasma CDR1as levels in patients with atherosclerosis with or without allergies. RESULTS: Asthma mice with a standard laboratory diet showed increased atherosclerotic lesions and inflammatory infiltration depending on IgE-FcεR1 signal. FcεR1 knockout mice and blockage of IgE-FcεR1 signaling with IgE monoclonal antibody, omalizumab, all significantly alleviated asthma-mediated atherosclerosis and vascular inflammatory remodeling. Anti-inflammation with dexamethasone and stabilization of MC with cromolyn partially alleviated atherosclerotic lesions and mitigated the inflammatory infiltration in arteries. Mechanistically, IgE stimulation upregulates MC CDR1as expression in exosomes and upregulates the endothelial cell adhesive factors VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) via the CDR1as-FUS (fused in sarcoma)-phos-p65 axis. Knockdown of CDR1as in vivo significantly decreased the endothelial adhesion function and mitigated asthma-mediated atherosclerosis. Furthermore, a cohort study indicated higher plasma CDR1as levels in patients with atherosclerosis with allergies than in patients with atherosclerosis and healthy controls. CONCLUSIONS: Exosomes from IgE-stimulated MCs aggravated atherosclerosis through circular RNA CDR1as-mediated endothelial dysfunction, providing a novel insight into asthma-mediated atherosclerosis and potential diagnostic and therapeutic targets.

Interplay of energy metabolism and autophagy.

Macroautophagy/autophagy, is widely recognized for its crucial role in enabling cell survival and maintaining cellular energy homeostasis during starvation or energy stress. Its regulation is intricately linked to cellular energy status. In this review, covering yeast, mammals, and plants, we aim to provide a comprehensive overview of the understanding of the roles and mechanisms of carbon- or glucose-deprivation related autophagy, showing how cells effectively respond to such challenges for survival. Further investigation is needed to determine the specific degraded substrates by autophagy during glucose or energy deprivation and the diverse roles and mechanisms during varying durations of energy starvation.Abbreviations: ADP: adenosine diphosphate; AMP: adenosine monophosphate; AMPK: AMP-activated protein kinase; ATG: autophagy related; ATP: adenosine triphosphate; ER: endoplasmic reticulum; ESCRT: endosomal sorting complex required for transport; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GD: glucose deprivation; GFP: green fluorescent protein; GTPases: guanosine triphosphatases; HK2: hexokinase 2; K phaffii: Komagataella phaffii; LD: lipid droplet; MAP1LC3/LC3: microtubule-associated protein1 light chain 3; MAPK: mitogen-activated protein kinase; Mec1: mitosis entry checkpoint 1; MTOR: mechanistic target of rapamycin kinase; NAD (+): nicotinamide adenine dinucleotide; OGD: oxygen and glucose deprivation; PAS: phagophore assembly site; PCD: programmed cell death; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; ROS: reactive oxygen species; S. cerevisiae: Saccharomyces cerevisiae; SIRT1: sirtuin 1; Snf1: sucrose non-fermenting 1; STK11/LKB1: serine/threonine kinase 11; TFEB: transcription factor EB; TORC1: target of rapamycin complex 1; ULK1: unc-51 like kinase 1; Vps27: vacuolar protein sorting 27; Vps4: vacuolar protein sorting 4.

Ten-year experiences and outcomes of bypass surgery and endovascular therapy in the management of infrarenal aortic occlusion: a single-center retrospective cohort study.

Background: Infrarenal aortic occlusion (IAO) is a life-threatening condition that often causes lower limb ischemia. Although open surgery is the current recommendation for first-line treatment, recent technological innovations have made endovascular treatment (EVT) a promising alternative. This study aims to compare the clinical outcomes of bypass surgery and EVT in the treatment of IAO. Methods: This study is a single-center retrospective observative study at Peking Union Medical College Hospital. Consecutive 92 patients with chronic and atherosclerotic IAO were treated with either EVT (n=40) or bypass surgery (n=52) between 2011 and 2021. The baseline clinical factors (including demographic data and comorbidities), perioperative data (including Rutherford classification changes, technical success) and complication rates were evaluated. The mid-term patency and overall survival of EVT and bypass were assessed. Follow-up was defined as the time from surgery to the last outpatient visit. Continuous variables and category variables were statistically compared, respectively. Kaplan-Meier survival analyses were conducted for vascular patency. Results: The study found that the demographics and pre-operative Rutherford classification were evenly distributed between the two groups (P>0.05). As for technical success, clinical success, comorbidities, mortality, complication rate, and Rutherford classification after procedures, no significant differences were observed (P>0.05). The average post-procedure hospital stay was 5.15 days in the EVT group and was significantly shorter than that of the bypass group, which was 11.83 days (P<0.0001). As for short-term and long-term results, the 1-, 3-, and 5-year primary patency rates were 81.8%, 73.1%, and 73.1% in the EVT group and 97.8%, 80.6%, and 80.6% in the bypass group. The bypass group had significantly better primary patency (P=0.034). There was a significant difference in the secondary patency rate (Bypass 100% vs. EVT 81.6%; P=0.005). Moreover, survival rates were higher in the bypass surgery group than in the EVT group (P=0.035). Conclusions: Although EVT's primary patency rate was lower than that with the bypass surgery, its safety and efficacy were still comparable to anatomic bypass surgery for IAO with less severe perioperative complications and shorter hospital stay. Therefore, EVT could be a feasible option for IAO.

A contrast-enhanced CT-based radiomic nomogram for the differential diagnosis of intravenous leiomyomatosis and uterine leiomyoma.

Objective: Uterine intravenous leiomyomatosis (IVL) is a rare and unique leiomyoma that is difficult to surgery due to its ability to extend into intra- and extra-uterine vasculature. And it is difficult to differentiate from uterine leiomyoma (LM) by conventional CT scanning, which results in a large number of missed diagnoses. This study aimed to evaluate the utility of a contrast-enhanced CT-based radiomic nomogram for preoperative differentiation of IVL and LM. Methods: 124 patients (37 IVL and 87 LM) were retrospectively enrolled in the study. Radiomic features were extracted from contrast-enhanced CT before surgery. Clinical, radiomic, and combined models were developed using LightGBM (Light Gradient Boosting Machine) algorithm to differentiate IVL and LM. The clinical and radiomic signatures were integrated into a nomogram. The diagnostic performance of the models was evaluated using the area under the curve (AUC) and decision curve analysis (DCA). Results: Clinical factors, such as symptoms, menopausal status, age, and selected imaging features, were found to have significant correlations with the differential diagnosis of IVL and LM. A total of 108 radiomic features were extracted from contrast-enhanced CT images and selected for analysis. 29 radiomics features were selected to establish the Rad-score. A clinical model was developed to discriminate IVL and LM (AUC=0.826). Radiomic models were used to effectively differentiate IVL and LM (AUC=0.980). This radiological nomogram combined the Rad-score with independent clinical factors showed better differentiation efficiency than the clinical model (AUC=0.985, p=0.046). Conclusion: This study provides evidence for the utility of a radiomic nomogram integrating clinical and radiomic signatures for differentiating IVL and LM with improved diagnostic accuracy. The nomogram may be useful in clinical decision-making and provide recommendations for clinical treatment.

Renal perfusion improvement in the perioperative period after unilateral endovascular revascularization in patients with atherosclerotic renal artery stenosis.

Background: The clinical benefits of endovascular treatment in renal artery stenosis (RAS) remain controversial. This study used an intraoperative renal perfusion imaging technique, called flat-panel detector parenchymal blood volume imaging (FD-PBV), to observe the change in renal perfusion after endovascular treatment in RAS. Materials and methods: In a prospective, single-center study, we assigned 30 patients with atherosclerotic RAS who underwent endovascular treatment between March 2016 and March 2021. The preoperative and postoperative results of renal perfusion, blood pressure, and renal function, were compared. Results: Both median kidney volume (p < 0.001) and median preoperative mean density of contrast medium (MDCM) (p = 0.028) increased significantly after endovascular treatment. The ratio of postoperative and preoperative MDCM differed greatly among the patients. For patients with preoperative MDCM <304.0 HU (Subgroup A, 15 cases), MDCM significantly increased after treatment (p = 0.001) and 12 (80.0%) patients had more than 10% increase in renal perfusion. For patients who had relatively high preoperative renal perfusion (MDCM ≥304.0 HU, Subgroup B, 15 cases), preoperative and postoperative MDCM were similar (p = 0.776). On the other hand, the serum creatinine levels significantly decreased in Subgroup A (p = 0.033) and fewer antihypertensive drugs were used after endovascular revascularization (p = 0.041). The preoperative and postoperative creatinine levels and number of antihypertensive drugs were similar in Subgroup B. Conclusions: During the perioperative period, RAS patients with relatively low preoperative renal perfusion levels had greater improvement in renal perfusion, renal function, and blood pressure control after endovascular treatment. The improvement of renal function needs to be confirmed by long-term follow-up.

Imbalance of helper T cell subtypes and adipokine secretion in perivascular adipose tissue as a trigger of atherosclerosis in chronic Porphyromonas gingivalis W83 infection.

Periodontal disease, a prevalent oral disease, is an independent risk factor for atherosclerosis. Porphyromonas gingivalis (P.g), a keystone pathogen of periodontal disease, contributes to the pathogenesis of atherosclerosis. However, the exact mechanism remains unclear. An increasing number of studies have proposed the atherogenic influence of perivascular adipose tissue (PVAT) in pathological conditions including hyperlipidemia and diabetes. Nevertheless, the role of PVAT in atherosclerosis promoted by P.g infection has not been explored. In our study, we investigated the association between P.g colonization in PVAT and progression of atherosclerosis through experiments on clinical samples. We further investigated P.g invasion of PVAT, PVAT inflammation, aortic endothelial inflammation, aortic lipid deposition, and systemic inflammation in C57BL/6 J mice with or without P.g infection at 20, 24, and 28 weeks of age. PVAT inflammation, characterized by imbalance in Th1/Treg and dysregulated adipokine levels, was associated with P.g invasion, preceding endothelial inflammation that occurred independently of its direct invasion. The phenotype of systemic inflammation coincided with that of PVAT inflammation, but systemic inflammation occurred after endothelial inflammation. Therefore PVAT inflammation in early atherosclerosis could be a primary trigger of aortic endothelial inflammation and lipid deposition in chronic P.g infection, through the dysregulated paracrine secretion of T helper-1-related adipokines.

The Correlation of Apolipoprotein B with Alterations in Specific Fat Depots Content in Adults.

Body mass index (BMI) and blood biomarkers are not enough to predict cardiovascular disease risk. Apolipoprotein B was identified to be associated with cardiovascular disease (CVD) progression. The Dual-energy X-ray Absorption (DXA) results could be considered as a predictor for cardiovascular disease in a more refined way based on fat distribution. The prediction of CVD risk by simple indicators still cannot meet clinical needs. The association of ApoB with specific fat depot features remains to be explored to better co-predict cardiovascular disease risk. An amount of 5997 adults from National Health and Nutrition Examination Survey (NHANES) were enrolled. Their demographic information, baseline clinical condition, blood examination, and DXA physical examination data were collected. Multivariate regression was used to assess the correlation between ApoB and site-specific fat characteristics through different adjusted models. Smooth curve fittings and threshold analysis were used to discover the turning points with 95% confidence intervals. ApoB is positively correlated with arms percent fat, legs percent fat, trunk percent fat, android percent fat, gynoid percent fat, arm circumference and waist circumference after adjustment with covariates for age, gender, race, hypertension, diabetes, hyperlipidemia, coronary heart disease, smoking status and vigorous work activity. The smooth curve fitting and threshold analysis also showed that depot-specific fat had lower turning points of ApoB in both males and females within the normal reference range of ApoB. Meanwhile, females have a lower increase in ApoB per 1% total percent fat and android percent fat than males before the turning points, while females have a higher growth of ApoB per 1% gynoid percent fat than males. The combined specific fat-depot DXA and ApoB analysis could indicate the risk of CVD in advance of lipid biomarkers or DXA alone.

Midterm Results of a Surgeon-Modified Device to Preserve the Flow of the Internal Iliac Artery During Endovascular Repair of Aneurysm: Single-Center Experiences.

BACKGROUND: During endovascular aneurysm repair (EVAR), commercial iliac branch devices (IBDs) have become an inescapable alternative for preserving antegrade internal iliac artery (IIA) blood flow. Due to the different morphological features of aneurysms, commercial IBDs may not be suitable for all patients. Reported experience with the implantation of the new surgeon-modified IBD (sm IBD) is limited. This investigation describes the indications, efficacy, and safety of the sm IBD. METHODS: Data from consecutive elective implantations of IBDs in patients between March 2011 and May 2021 in a single center were incorporated. The sm IBDs were indicated in patients with common iliac artery aneurysms (CIAAs) and with a challenging anatomy and in those patients with or without abdominal aortic aneurysm (AAA). RESULTS: Fifteen patients (15 male, mean age 67.6 ± 7.9 years) were included. Fifteen sm IBDs were implanted in 1 procedure (100%). Fourteen (93.3%) patients had simultaneous endovascular aneurysm repair (EVAR) and 1 (6.7%) patient previously had a bilateral CIAAs repair by EVAR. The mean common iliac artery (CIA) diameter was 36.6 ± 12.5 mm. Technical success was obtained in all patients (100%). The median operation time was 189.7 ± 78.6 min, with a median fluoroscopy time of 45.3 ± 15.9 min. Axillary artery access was used in 11 (73.3%) procedures. The mean total hospital stay was 5.6 ± 2.8 days, and the postoperative follow-up was 35.4 months (range 2-120). The estimated IIA bridge stent patency at 1 year after operation was 100% and 85.7% ± 13.2% 5 years postoperatively. One (6.7%) IIA branch was occluded, and this patient remained asymptomatic. One patient (6.7%) needed reintervention, and another (6.7%) patient had type II leakage, which is currently under close surveillance. CONCLUSIONS: Using an IBD to maintain the pelvic blood flow is an effective and feasible intravascular technique, especially for patients with an abnormal iliac artery anatomy. This novel technique has similar midterm procedural success rate compared to the use of commercial IBDs. Therefore, these devices are more suitable for patients with certain anatomic challenges and can be used as an alternative treatment.

Angiosome-directed endovascular intervention and infrapopliteal disease: Intraoperative evaluation of distal hemodynamic changes and foot blood volume of lower extremity.

Objectives: To evaluate foot blood volume and hemodynamics and explore whether quantitative techniques can guide revascularization. Materials and methods: A prospective single-center cohort study included thirty-three patients with infrapopliteal artery occlusion who underwent percutaneous transluminal angioplasty (PTA) between November 2016 and May 2020. The time-to-peak (TTP) from color-coded quantitative digital subtraction angiography (CCQ-DSA) and parenchymal blood volume (PBV) were used to evaluate the blood volume and hemodynamic changes in different regions of the foot before and after the operation. Results: After the intervention procedure, the overall blood volume significantly increased from 25.15 ± 21.1 ml/1,000 ml to 72.33 ± 29.3 ml/1,000 ml (p < 0.001, with an average increase of 47.18 ml/1,000 ml. The overall TTP decrease rate, postoperative blood flow time significantly faster than those preoperatively, from 22.93 ± 7.83 to 14.85 ± 5.9 s (p < 0.001, with an average decrease of 8.08 s). Direct revascularization (DR) resulted in significant blood volume improvement than compared with indirect revascularization (IR) [188% (28, 320) vs.51% (10, 110), p = 0.029]. Patients with DR had a significantly faster blood flow time than those with IR [80% (12, 180) vs. 26% (5, 80), p = 0.032]. The ankle-brachial index (ABI) of the affected extremity also showed an significant change from 0.49 ± 0.3 to 0.63 ± 0.24 (p < 0.001) after the intervention. The relative values of ΔTTP and ΔABI showed a weak correlation (r = -0.330). Conclusions: The quantitative measurement results based on PBV and CCQ-DSA techniques showed that the overall blood volume increased significantly and that the foot distal hemodynamics were significantly improved after endovascular treatment. DR in the ischemic area could r improve foot perfusion.

Impaired pedal arch affects the treatment effect in patients with single tibial artery revascularization demonstrated by intraoperative perfusion.

Background: The treatment strategy for patients with multiple infrapopliteal artery occlusions remains controversial. In this study, we investigated how anatomic factors affect the treatment effect of infrapopliteal artery intervention and identified suitable intervention strategies for patients with multiple infrapopliteal artery occlusions. Methods: This was a prospective, single-center, observational cohort study. For each patient, the intrainterventional blood volume improvement of the dorsum and plantar surface was measured and classified into the direct perfused region (DR) or indirect perfused region (IR) on the basis of whether the supplying artery was revascularized. Digital subtraction angiography was performed to analyze how pedal arch patency affects blood communication between DR and IR. Results: A total of 38 patients treated with infrapopliteal intervention at the Department of Vascular Surgery of Peking Union Medical College Hospital from November 2016 to November 2020 were considered for inclusion in this study. Finally, 26 patients were included in the analysis. In patients with type III pedal arch, blood volume improvements for DR and IR were 70.50 (17.50, 191.75) and 11.25 (-10.25, 50.25) mL/1,000 mL, respectively (P=0.018). No significant difference was found between DR and IR in patients with type I pedal arch (P=0.208) and type II pedal arch (P=0.110). Conclusions: Impaired pedal arch has an adverse impact on foot collateral circulation. Patients with these conditions are more suitable for direct revascularization than other patients. Trial Registration: ClinicalTrials.gov identifier: NCT03248323.

Irisin Suppresses Nicotine-Mediated Atherosclerosis by Attenuating Endothelial Cell Migration, Proliferation, Cell Cycle Arrest, and Cell Senescence.

Atherosclerotic disease has become the major cause of death worldwide. Smoking, as a widespread independent risk factor, further strengthens the health burden of atherosclerosis. Irisin is a cytokine that increases after physical activity and shows an atheroprotective effect, while its specific mechanism in the process of atherosclerosis is little known. The reversal effect of irisin on intimal thickening induced by smoking-mediated atherosclerosis was identified in Apoe -/- mice through the integrin αVß5 receptor. Endothelial cells treated with nicotine and irisin were further subjected to RNA-seq for further illustrating the potential mechanism of irisin in atherosclerosis, as well as the wound healing assays, CCK-8 assays, ß-gal staining and cell cycle determination to confirm phenotypic alterations. Endothelial differential expressed gene enrichment showed focal adhesion for migration and proliferation, as well as the P53 signaling pathway for cell senescence and cell cycle control. Irisin exerts antagonistic effects on nicotine-mediated migration and proliferation via the integrin αVß5/PI3K pathway. In addition, irisin inhibits nicotine-mediated endothelial senescence and cell cycle arrest in G0/G1 phase via P53/P21 pathway. This study further illustrates the molecular mechanism of irisin in atherosclerosis and stresses its potential as an anti-atherosclerotic therapy.

Irisin ameliorates nicotine-mediated atherosclerosis via inhibition of the PI3K pathway.

BACKGROUND: Atherosclerosis is a chronic disease, with smoking being an independent risk factor. Irisin, a factor produced by myocytes, is expected to treat smoking-related arteriosclerosis, however its specific mechanism remains unclear. METHODS: Forty Apoe-/- mice with nicotine intervention were involved in this study. The atherosclerotic lesions, smooth muscle cell proliferation, and macrophage infiltration induced by nicotine, and the corresponding changes caused by the administration of irisin, were obtained. The integrin αVß5 inhibitor, cilengitide, was included to determine the cell entry pathway of irisin. Proteins and mRNA levels of phosphatidylinositol 3-kinase (PI3K) and downstreams were detected to clarify the specific molecular mechanism of irisin activity. RESULTS: H&E staining and Masson staining showed that nicotine could aggravate the intensity of atherosclerosis in mice, and Irisin could reverse the thickening of the vascular media induced by nicotine. Immunohistochemical staining of CD68 and α-SMA suggested that Irisin could inhibit nicotine-mediated macrophage infiltration and smooth muscle cell proliferation. The protective effect of Irisin was partially reduced after the administration of cilengitide, confirming that Irisin enters cells through multiple ways, including integrin αvß5. Nicotine was confirmed to activate the PI3K pathway to promote media thickening, while Irisin can inhibit the activation of the PI3K pathway, thus playing its anti-atherosclerosis role. Irisin was further observed to reverse nicotine-mediated P27 down-regulation. CONCLUSIONS: Irisin was found to inhibit nicotine-mediated medium thickening, smooth muscle cell proliferation, macrophage infiltration, and atherosclerosis progression via the integrin αVß5/PI3K/P27 pathway.

Current knowledge of Krüppel-like factor 5 and vascular remodeling: providing insights for therapeutic strategies.

Vascular remodeling is a pathological basis of various disorders. Therefore, it is necessary to understand the occurrence, prevention, and treatment of vascular remodeling. Krüppel-like factor 5 (KLF5) has been identified as a significant factor in cardiovascular diseases during the last two decades. This review provides a mechanism network of function and regulation of KLF5 in vascular remodeling based on newly published data and gives a summary of its potential therapeutic applications. KLF5 modulates numerous biological processes, which play essential parts in the development of vascular remodeling, such as cell proliferation, phenotype switch, extracellular matrix deposition, inflammation, and angiogenesis by altering downstream genes and signaling pathways. Considering its essential functions, KLF5 could be developed as a potent therapeutic target in vascular disorders.

Long-term outcomes of conservative treatment and endovascular treatment in patients with symptomatic spontaneous isolated superior mesenteric artery dissection: a single-center experience.

BACKGROUND: Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare vascular disorder, and the treatment strategies remain controversial. This study aimed to compare outcomes of conservative and endovascular treatments in symptomatic patients with SISMAD. METHODS: Forty-two consecutive SISMAD patients who were admitted to a single center between October 2009 and May 2018 were enrolled in this study. Based on their symptoms, 15 had conservative treatment, and 27 had endovascular treatment. The baseline characteristics, treatments, and follow-up results of the conservative group and endovascular group were analysed. RESULTS: The rates of symptom relief were 93.3% in the conservative group and 96.3% in the endovascular group. The procedure-related complications in the endovascular group included one case of pseudoaneurysm formation in the left brachial artery. During the follow-up period (median 28.5 months), a higher proportion of patients in the conservative group had symptom recurrence (42.9% in the conservative group versus 4.8% in the endovascular group, p < 0.001). Four patients in the conservative group and one patient in the endovascular group had additional endovascular intervention during follow-up. Compared with the conservative group, patients in the endovascular group had statistically significantly longer symptom-free survival (p = 0.014) and a higher rate of superior mesenteric artery (SMA) remodeling (p < 0.001). CONCLUSIONS: For symptomatic SISMAD, endovascularly treated patients had a lower rate of symptom recurrence and a higher rate of SMA remodeling in the long term. Prospective, multi-center studies are needed to confirm the long-term outcomes of both treatments.

Downregulation of TSPO expression inhibits oxidative stress and maintains mitochondrial homeostasis in cardiomyocytes subjected to anoxia/reoxygenation injury.

Translocator protein (TSPO) is highly expressed in the cardiovascular system, exerting crucial effects on both myocardial damage and protection. However, the role and mechanism of TSPO in myocardial ischemia/reperfusion (I/R) injury remains elusive. In the current study, we subjected H9c2 cardiomyocytes to anoxia/reoxygenation (A/R) and knocked down TSPO expression by RNA interference to investigate the possible mechanism of TSPO on I/R injury. TSPO expression in cardiomyocytes was up-regulated when exposed to A/R, but normal in anoxic preconditioned (APC) cardiomyocytes. Moreover, A/R also led to an increase in reactive oxygen species (ROS), oxidative stress aggravation, mitochondrial membrane potential collapse, mitochondrial permeability transition pore (mPTP) opening, and cell apoptosis. However, these events were completely compensated by downregulating TSPO expression. TSPO-downregulated cardiomyocytes produced lesser lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), and showed lesser cytosol malondialdehyde (MDA) accumulation than normal cells after A/R injury. On the other hand, the TSPO- downregulated cells showed higher activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), mitochondrial function stabilization, resulting in less cell apoptosis and damage in case of A/R condition. In conclusion, TSPO expression is up-regulated under A/R injury, whereas repression of TSPO improves the endurance of cardiomyocytes against A/R injury by reducing oxidative stress, mitochondrial damage and cell apoptosis.

Vimentin-positive circulating tumor cells as a biomarker for diagnosis and treatment monitoring in patients with pancreatic cancer.

The identification of circulating tumor cells (CTCs) relies on epithelial tumor cell markers. In the present study, we aimed to determine whether cell-surface vimentin could be a biomarker to isolate CTCs in pancreatic ductal adenocarcinoma (PDAC). Vimentin was identified as highly expressed on the surface of mesenchymal-phenotype pancreatic tumor cells. Vimentin+ CTCs were detected in 76% of patients with PDAC (76/100) using CTCs enriched via a microfluidic assay. A cut-off value of two vimentin+ CTCs distinguished patients with PDAC from healthy individuals. Combined vimentin+ CTCs and Carbohydrate antigen 19-9 provided favorable diagnostic potency, with an area under the curve of 0.968. Vimentin+ CTCs counts correlated with the change in tumor burden for patients undergoing resection. Significantly reduced CTC counts were observed after chemotherapy in subjects that responded to treatment. Preoperatively higher CTCs counts correlated with shortened recurrence-free survival. Taken together, vimentin+ CTCs could be a reliable biomarker in pancreatic cancer. The enrichment of mesenchymal CTCs complements the strategy of capturing epithelial CTCs, allowing a more thorough interrogation of the biology and clinical significance of CTCs in PDAC.

Cobalt substitution in a flexible metal-organic framework: modulating a soft paddle-wheel unit for tunable gate-opening adsorption.

Developing feasible ways to achieve tunable gate-opening pressure (Pgo) while minimizing the side effects on the adsorption capacity and enthalpy is greatly desired for flexible MOFs. In this work, we focused on solving this issue by cobalt substitution. We showed the successful modulation of the energy required for the reversible transformation of a soft paddle-wheel so that the whole framework presented a substitution-dependent Pgo for CO2 adsorption.

Molecular mechanisms of FOXO1 in adipocyte differentiation.

Forkhead box-O1 (FOXO1) is a downstream target of AKT and plays crucial roles in cell cycle control, apoptosis, metabolism and adipocyte differentiation. It is thought that FOXO1 affects adipocyte differentiation by regulating lipogenesis and cell cycle. With the deepening in the understanding of this field, it is currently believed that FOXO1 translocation between nuclei and cytoplasm is involved in the regulation of FOXO1 activity, thus affecting adipocyte differentiation. Translocation of FOXO1 depends on its post-translational modifications and interactions with 14-3-3. Based on these modifications and interactions, FOXO1 could regulate lipogenesis through PPARγ and the adipocyte cell cycle through p21 and p27. In this review, we aim to provide a comprehensive FOXO1 regulation network in adipocyte differentiation by linking together distinct functions mentioned above to explain their effects on adipocyte differentiation and to emphasize the regulatory role of FOXO1. In addition, we also focus on the novel findings such as the use of miRNAs in FOXO1 regulation and highlight the improvable issues, such as RNA modifications, for future research in the field.