Search

Abstract Abdominal aortic aneurysms (AAA) are a significant health concern in developed countries due to their considerable mortality rate. The crucial factor of the progression of AAA is the release of neutrophils and neutrophil extracellular traps (NETs). Magnetic particle imaging (MPI) is a new imaging technique that offers the capability to detect superparamagnetic iron oxide nanoparticles (SPION) with exceptional sensitivity. We aimed to investigate the functional imaging of MPI for the detection and monitoring of neutrophil infiltration within AAA. A novel multimodal imaging agent targeting neutrophils, PEG-Fe3O4-Ly6G–Cy7 nanoparticles (Ly6G NPs), were designed by coupling Fe3O4 nanoparticles with Ly6G antibodies and Cy7. The targeting and sensitivity of Ly6G NPs were assessed using MPI and fluorescence imaging (FLI) in the AAA mouse model. After the inhibition of NETosis, the degree of neutrophil infiltration and AAA severity were assessed using MPI with Ly6G NPs. Ly6G NPs accurately localized and quantitatively analyzed AAA lesion sites in mice using MPI/FLI/CT. Compared to the control group, elevated MPI and FLI signal intensities were detected at the abdominal aortic lesion site, and neutrophil infiltration and NETs accumulation were detected by histological analysis in the AAA models. After the inhibition of NETs accumulation in vivo, pathological damage in the abdominal aorta was significantly reduced, along with a decrease in the accumulation of Ly6G NPs and MPI signals. This multimodal MPI strategy revealed that nanoparticles targeting Ly6G can be used to detect neutrophil infiltration within AAA and monitor AAA severity.

MethodsWe recruited 58 MA-dependent young adult females from a compulsory isolation drug rehabilitation center in Sichuan Province and randomly divided them into an MBRP group (n = 29) and a control group (n = 29) according to their degree of psychological craving. The MBRP group received 2 hours of MBRP training twice a week for 4 weeks, alongside routine treatment at the drug rehabilitation center. Meanwhile, the control group solely received routine treatment at the drug rehabilitation center without any additional interventions. The assessment was conducted before and immediately after the intervention, with the Compulsive Drug Use Scale (OCDUS) used to assess craving and the Five-Factor Mindfulness Scale (FFMQ) used to assess trait mindfulness. Also, a “mental feedback monitoring balance” instrument was used to assess concentration and relaxation during some training sessions. This randomized trial was conducted to evaluate the effectiveness of decreasing psychological craving and increasing trait mindfulness.ResultsAt baseline, there were no significant differences in total or dimension scores for FFMQ or OCDUS between the two groups (all P > 0.05). After the intervention, the repeated measures ANOVA showed a significant time main effect on changes in observing, non-judging, and non-reacting scores (all P < 0.05), and a significant interaction effect between time and group on both FFMQ total score and OCDUS score (P < 0.01 or P < 0.05). Mental feedback monitoring indicated significant improvement in concentration and relaxation after breath meditation exercises (P < 0.05 or P < 0.001). Additionally, the MBRP group showed improved relaxation during the body scan exercise (P < 0.01).ConclusionMBRP training can improve the trait mindfulness of MA addicts and reduce psychological cravings effectively.

Lower extremity peripheral artery disease (PAD) is a growing global health problem. New methods to diagnose PAD have been explored in recent years. At present, the majority of imaging methods for PAD focus on the macrovascular blood flow, and the exploration of microcirculation and tissue perfusion of PAD remains largely insufficient. In this report, we applied three new imaging technologies, i.e., second near-infrared region (NIR-II, 900–1,880 nm wavelengths) imaging, optical coherence tomography angiography (OCTA), and laser speckle flowgraphy (LSFG), in a PAD patient with a healthy human subject as control. Our results showed that the PAD patient had poorer tissue perfusion than the control without observed adverse effects. Moreover, compared with the first near-infrared region (NIR-I, 700–900 nm wavelengths) imaging results, NIR-II imaging had a higher signal-to-background ratio and resolution than NIR-I imaging and detected microvessels that were not detected by NIR-I imaging. These observations suggested that NIR-II imaging, OCTA, and LSFG are potentially safe and effective methods for diagnosing PAD.

Abstract Background Atherosclerosis (AS) is a persistent inflammatory condition triggered and exacerbated by several factors including lipid accumulation, endothelial dysfunction and macrophages infiltration. Nobiletin (NOB) has been reported to alleviate atherosclerosis; however, the underlying mechanism remains incompletely understood. Methods This study involved comprehensive bioinformatic analysis, including multidatabase target prediction; GO and KEGG enrichment analyses for function and pathway exploration; DeepSite and AutoDock for drug binding site prediction; and CIBERSORT for immune cell involvement. In addition, target intervention was verified via cell scratch assays, oil red O staining, ELISA, flow cytometry, qRT‒PCR and Western blotting. In addition, by establishing a mouse model of AS, it was demonstrated that NOB attenuated lipid accumulation and the extent of atherosclerotic lesions. Results (1) Altogether, 141 potentially targetable genes were identified through which NOB could intervene in atherosclerosis. (2) Lipid and atherosclerosis, fluid shear stress and atherosclerosis may be the dominant pathways and potential mechanisms. (3) ALB, AKT1, CASP3 and 7 other genes were identified as the top 10 target genes. (4) Six genes, including PPARG, MMP9, SRC and 3 other genes, were related to the M0 fraction. (5) CD36 and PPARG were upregulated in atherosclerosis samples compared to the normal control. (6) By inhibiting lipid uptake in RAW264.7 cells, NOB prevents the formation of foam cell. (7) In RAW264.7 cells, the inhibitory effect of oxidized low-density lipoprotein on foam cells formation and lipid accumulation was closely associated with the PPARG signaling pathway. (8) In vivo validation showed that NOB significantly attenuated intra-arterial lipid accumulation and macrophage infiltration and reduced CD36 expression. Conclusions Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

BackgroundAtherosclerosis (AS) is a chronic arterial pathology and a leading cause of vascular disease-related mortality. Fatty streaks in the arterial wall develop into atherosclerosis and characteristic plaques. Clinical interventions typically involve lipid-lowering medications and drugs for stabilizing vulnerable plaques, but no direct therapeutic agent specifically targets atherosclerosis. Garlic, also locally known as DASUAN, is recognized as a widely sold herbal dietary supplement esteemed for its cardiovascular benefits. However, the specific mechanisms of garlic’s anti-atherosclerotic effects remain unclear.AimsThis study aims to elucidate the pharmacological mechanisms through which garlic ameliorates atherosclerosis.MethodsThe study identified the major active components and targets of garlic by screening the TCMSP, TCM-ID, and, ETCM databases. Atherosclerosis-associated targets were obtained from the DisGeNET, GeneCards, and DiGSeE databases, and garlic intervention targets were determined through intersection. Utilizing the intersected genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using R software. A garlic component-disease target network was constructed using Cytoscape. RNA-seq datasets from the GEO database were utilized to identify differentially expressed genes (DEGs) associated with atherosclerosis. The target genes were intersected with DEGs and the FerrDb (ferroptosis database). Molecular docking predicted the binding interactions between active components and the core targets. In vitro and in vivo experiments validated the identified core targets.ResultsThe integration of garlic drug targets with atherosclerotic disease targets identified 230 target genes. Intersection with RNA-seq DEGs revealed 15 upregulated genes, including 8 target genes related to ferroptosis. Molecular docking indicated favorable affinities between garlic active components [Sobrol A, (+)-L-Alliin, Benzaldoxime, Allicin] and target genes (DPP4, ALOX5, GPX4). Experimental validation showed that GARLIC reduces the expression of ferroptosis-related genes in AS, suggesting its therapeutic potential through the regulation of ferroptosis.ConclusionGarlic ameliorates atherosclerosis by targeting intra-plaque ferroptosis and reducing lipid peroxidation. These findings provide novel insights into the pharmacological mechanisms underlying the efficacy of garlic in treating AS.

BackgroundBile acids (BAs), products of gut microbiota metabolism, have long been implicated in atherosclerotic disease pathogenesis. Characterizing the serum bile acid profile and exploring its potential role in carotid atherosclerosis (CAS) development are crucial tasks.MethodsIn this study, we recruited 73 patients with CAS as the disease group and 77 healthy individuals as the control group. We systematically measured the serum concentrations of 15 bile acids using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression were applied to analyze the impact of bile acids on the disease and select the key BAs. The possible molecular mechanism was elucidated by network pharmacology.Results(1) The BA profile of patients with CAS significantly differed. (2) Multifactorial logistic regression analysis identified elevated levels of GCDCA (OR: 1.01, P < 0.001), DCA (OR: 1.01, P = 0.005), and TDCA (OR: 1.05, P = 0.002) as independent risk factors for CAS development. Conversely, GCA (OR: 0.99, P = 0.020), LCA (OR: 0.83, P = 0.002), and GUDCA (OR: 0.99, P = 0.003) were associated with protective effects against the disease. GCA, DCA, LCA, and TDCA were identified as the four key BAs. (3) TNF, FXR, GPBAR1, ESR1 and ACE were predicted to be targets of BAs against AS. These four BAs potentially impact AS progression by triggering signaling pathways, including cAMP, PPAR, and PI3K-AKT pathways, via their targets.ConclusionThis study offers valuable insights into potential therapeutic strategies for atherosclerosis that target bile acids.

AbstractContrast-induced acute kidney injury (CI-AKI) has become the third leading cause of hospital-acquired kidney injury. A comprehensive analysis of the current state of research in the field of CI-AKI will help to reveal trends and hot topics in the field. To date, there are no published bibliometric analyses related to CI-AKI studies. Here, we analyze the relevant literature since the emergence of the concept and provide valuable insights. The literature was collected from the Web of Science Core Collection. The data were analyzed visually using CiteSpace and VOSviewer software. We collected a total of 4775 papers, with the United States and Guangdong Acad Med Sci as the major publishing powers in terms of country/region and institution. J AM COLL CARDIOL was the journal with the most published and cocited articles. Cluster analysis showed that clinical trials are the current research hotspot. The areas of risk assessment, prevention strategies, risk factors, and vascular lesions have been popular in recent years. Research on the mechanism of injury in CI-AKI will be the focus of future research, which will be crucial to reduce the clinical incidence of CI-AKI. In summary, this study provides a comprehensive analysis of the development process in the field of CI-AKI and discusses future research directions based on the analysis of objective data from many studies on CI-AKI.

Abstract Background and objectives Phenotypic switching in vascular smooth muscle cells (VSMCs) has been linked to aortic aneurysm, but the phenotypic landscape in aortic aneurysm is poorly understood. The present study aimed to analyse the phenotypic landscape, phenotypic differentiation trajectory, and potential functions of various VSMCs phenotypes in aortic aneurysm. Methods Single-cell sequencing data of 12 aortic aneurysm samples and 5 normal aorta samples (obtained from GSE166676 and GSE155468) were integrated by the R package Harmony. VSMCs were identified according to the expression levels of ACTA2 and MYH11. VSMCs clustering was determined by the R package ‘Seurat’. Cell annotation was determined by the R package ‘singleR’ and background knowledge of VSMCs phenotypic switching. The secretion of collagen, proteinases, and chemokines by each VSMCs phenotype was assessed. Cell‒cell junctions and cell–matrix junctions were also scored by examining the expression of adhesion genes. Trajectory analysis was performed by the R package ‘Monocle2’. qPCR was used to quantify VSMCs markers. RNA fluorescence in situ hybridization (RNA FISH) was performed to determine the spatial localization of vital VSMCs phenotypes in aortic aneurysms. Results A total of 7150 VSMCs were categorize into 6 phenotypes: contractile VSMCs, fibroblast-like VSMCs, T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs. The proportions of T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs were significantly increased in aortic aneurysm. Fibroblast-like VSMCs secreted abundant amounts of collagens. T-cell-like VSMCs and macrophage-like VSMCs were characterized by high chemokine levels and proinflammatory effects. Adipocyte-like VSMCs and mesenchymal-like VSMCs were associated with high proteinase levels. RNA FISH validated the presence of T-cell-like VSMCs and macrophage-like VSMCs in the tunica media and the presence of mesenchymal-like VSMCs in the tunica media and tunica adventitia. Conclusion A variety of VSMCs phenotypes are involved in the formation of aortic aneurysm. T-cell-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs play pivotal roles in this process. Video Abstract

Abstract Vascular smooth muscle cells (VSMCs) are the most abundant cell in vessels. Earlier experiments have found that VSMCs possess high plasticity. Vascular injury stimulates VSMCs to switch into a dedifferentiated type, also known as synthetic VSMCs, with a high migration and proliferation capacity for repairing vascular injury. In recent years, largely owing to rapid technological advances in single-cell sequencing and cell-lineage tracing techniques, multiple VSMCs phenotypes have been uncovered in vascular aging, atherosclerosis (AS), aortic aneurysm (AA), etc. These VSMCs all down-regulate contractile proteins such as α-SMA and calponin1, and obtain specific markers and similar cellular functions of osteoblast, fibroblast, macrophage, and mesenchymal cells. This highly plastic phenotype transformation is regulated by a complex network consisting of circulating plasma substances, transcription factors, growth factors, inflammatory factors, non-coding RNAs, integrin family, and Notch pathway. This review focuses on phenotypic characteristics, molecular profile and the functional role of VSMCs phenotype landscape; the molecular mechanism regulating VSMCs phenotype switching; and the contribution of VSMCs phenotype switching to vascular aging, AS, and AA. Video Abstract

Nanotheranostic agents capable of simultaneously enabling real-time tracking and precise treatment at tumor sites play an increasingly pivotal role in the field of medicine. In this article, we report a novel near-infrared-II window (NIR-II) emitting downconversion rare-earth nanoparticles (RENPs) to improve image-guided therapy for breast cancer. The developed α-NaErF4@NaYF4 nanoparticles (α-Er NPs) have a diameter of approximately 24.1 nm and exhibit superior biocompatibility and negligible toxicity. RENPs exhibit superior imaging quality and photothermal conversion efficiency in the NIR-II range compared to clinically approved indocyanine green (ICG). Under 808 nm laser irradiation, the α-Er NPs achieve significant tumor imaging performance and photothermal effects in vivo in a mouse model of breast cancer. Simultaneously, it combines X-ray computed tomography (CT) and ultrasound (US) tri-modal imaging to guide therapy for cancer. The integration of NIR-II imaging technology and RENPs establishes a promising foundation for future medical applications.

Background Occupational health impairment of medical personnel manifested as a prominent problem in COVID-19. The aim of this study is to investigate the occupational physical injuries of front-line medical staffs in Hubei province during the fight against COVID-19. Material and Methods questionnaire survey was conducted among 476 medical staffs from 3 regions of Hubei Province, including general characteristics and the physical discomfort/damage suffered in the isolation wards during working hours. Results A total of 457 valid questionnaires were collected. The common physical discomfort/damage included skin injuries (22.76%), conjunctivitis (15.10%), falls (9.19%), intolerant unwell symptoms (8.53%) and sharp injuries (6.13%). Logistic regression analysis showed that: lack of protective work experience (OR = 2.049, 95% CI: 1.071–3.921), continuous working for 4 h (OR = 3.771, 95% CI: 1.858–7.654), and working >4 h (OR = 7.076, 95% CI: 3.197–15.663) were high-risk factors for skin injuries. Working continuously for 4 h (OR = 3.248, 95% CI: 1.484–7.110) and working >4 h (OR = 3.096, 95% CI: 1.232–7.772) were high-risk factors for conjunctivitis. Lack of protective work experience was a high risk factor for falls (OR = 5.508, 95% CI: 1.299–23.354). The high risk factors for intolerant unwell symptoms were continuous working for 4 h (OR = 5.372, 95% CI: 1.239–23.301) and working >4 h (OR = 8.608, 95% CI: 1.843–40.217). Working in a COVID-19 critical care unit (OR = 3.249, 95% CI: 1.344–7.854) and implementation of nursing (OR = 9.766, 95% CI: 1.307–72.984) were high risk factors for sharp injuries. Conclusions Occupational physical injuries are universal in the COVID-19 ward. Those who take up nursing, work in a critical care ward, with no experience in an isolation ward for infectious diseases, and work continuously for ≥4 h on the same day should get more attention. Med Pr. 2022;73(3):209–18

Vitamin D deficiency is prevalent in patients with chronic spinal cord injury (SCI) and has been implicated as an aetiologic factor of osteoporosis and various skeletal and extra-skeletal issues in SCI patients. Few data were available regarding vitamin D status in patients with acute SCI or immediately assessed at hospital admission. This retrospective cross-sectional study evaluated vitamin D status in SCI patients at admission to a UK SCI centre in January–December 2017. A total of 196 eligible patients with serum 25(OH)D concentration records at admission were recruited. The results found that 24 % were vitamin D deficient (serum 25(OH)D < 25 nmol/l), 57 % of the patients had serum 25(OH)D < 50 nmol/l. The male patients, patients admitted in the winter–spring time (December–May), and patients with serum sodium < 135 mmol/l or with non-traumatic causes had a significant higher prevalence of vitamin D deficiency than their counterparts (28 % males v. 11⋅8 % females, P = 0⋅02; 30⋅2 % in winter–spring v. 12⋅9 % in summer–autumn, P = 0⋅007; 32⋅1 % non-traumatic v. 17⋅6 % traumatic SCI, P = 0⋅03; 38⋅9 % low serum sodium v. 18⋅8 % normal serum sodium, P = 0⋅010). There was a significant inverse association of serum 25(OH)D concentration with body mass index (BMI) (r = −0⋅311, P = 0⋅002), serum total cholesterol (r = −0⋅168, P = 0⋅04) and creatinine concentrations (r = −0⋅162, P = 0⋅02) that were also significant predictors of serum 25(OH)D concentration. Strategies for systematic screening and efficacy of vitamin D supplementation in SCI patients need to be implemented and further investigated to prevent the vitamin D deficiency-related chronic complications.

ObjectivesThis study aims to investigate the influence of vitamin D supplementation on immune function of healthy older adults.Materials and methodsDesigned as a randomized controlled trial, 21 participants (55–85 years) completed the study during May–November 2018 in Coventry, England. The participants were randomized into vitamin D or the control group, stratified by age, gender and body mass index. The vitamin D group (n = 12) took vitamin D3 tablets of 1,000 IU/day for 12 weeks plus vitamin D education leaflet, while the control group (n = 9) were only provided with the leaflet. At baseline, 6 and 12 weeks, plasma 25(OH)D levels and immunological and metabolic parameters including phagocytic activity of granulocytes and monocytes, tumor necrosis factor, interleukin 6, lymphocyte subsets and fasting blood glucose and lipid were measured. Dietary vitamin D intake was analyzed at baseline and week 12. Data were presented as mean ± SD. Two-way repeated measures ANOVA and independent t-test were used to analyze the data.ResultsAt baseline, 42.9% of the participants were vitamin D deficiency (25(OH)D < 25 nmol/L), only 10% achieved a level of 25(OH)D > 50 nmol/L. Overweight/obese participants (n = 9) had significantly lower mean plasma 25(OH)D concentration (22.3 ± 8.7 nmol/L) than normal weight participants (48.1 ± 34.3 nmol/L) (P = 0.043). There was a significant increase in plasma 25(OH)D concentration in vitamin D group compared with that in control group (P = 0.002) during the intervention period. The plasma 25(OH)D concentration in vitamin D group was increased at 6 weeks (from 38.4 ± 37.0 nmol/L at baseline to 51.0 ± 38.2 nmol/L) with little change observed between 6 and 12 weeks (51.8 ± 36.4 nmol/L). The plasma creatinine concentration in vitamin D group was significantly decreased compared with the control group (P = 0.036) (79.8 ± 7.0 μmol/L at baseline vs 75.1 ± 5.4 μmol/L at week 12). No significant effect of vitamin D supplementation was determined on immunological parameters.ConclusionVitamin D deficiency is common among the aging population in the UK even during the summertime. Vitamin D supplementation at 1,000 IU/day for 12 weeks significantly increased plasma 25(OH)D concentration but showed no effect on metabolic and immunological parameters except decreased plasma creatinine.

BackgroundRecent studies have shown that in-stent neoatherosclerosis (ISNA/NA) is an important cause of late stent failure. A comprehensive understanding of the current state of research in this field will facilitate the analysis of its development trends and hot frontiers. However, no bibliometric correlation has been reported yet. Here, we analyze the relevant literature since the emergence of the concept and provide valuable insights.MethodsPublications were collected from the Web of Science Core Collection (WoSCC) and PubMed. Microsoft Excel, SPSS and CiteSpace were used to analyze and present the data.ResultsA total of 498 articles were collected, with Japan and Cardiovasc Res Fdn being the main publishing forces in all country/region and institutions. J AM COLL CARDIOL is the journal with the most published and co-cited articles. According to co-citation analysis, optical coherence tomography, thrombosis, implantation, restenosis, drug-eluting stent, and bare metal stent have become more and more popular recently.ConclusionISNA is a niche and emerging field. How to reduce the incidence of ISNA and improve the late patency rate of coronary stents may remain a hot spot for future research. The pathogenesis of ISNA also needs to be explored in more depth.

BackgroundVascular smooth muscle cell (VSMC) phenotype switching has been preliminarily found in aortic aneurysms. However, two major questions were raised: (1) What factors drive phenotypic switching of VSMCs in aortic aneurysms? (2) What role does VSMC phenotype transformation play in aortic aneurysms? We speculated that the interaction between infiltrated immune cells and VSMCs played a pivotal role in aortic aneurysm expansion.Materials and MethodsWe obtained single-cell transcriptome data GSE155468 that incorporate eight aortic aneurysm samples and three normal aorta samples. A standard single-cell analysis procedure was performed by Seurat (v3.1.2) for identifying the general cell components. Subsequently, VSMCs were extracted separately and re-clustered for identifying switched VSMC phenotypes. VSMC phenotype annotation was relied on the definitions of specific VSMC phenotypes in published articles. Vital VSMC phenotypes were validated by immunofluorescence. Next, identified immune cells and annotated vital VSMC phenotypes were extracted for analyzing the intercellular communication. R package CellChat (v1.1.3) was used for investigating the communication strength, signaling pathways, and communication patterns between various VSMC phenotypes and immune cells.ResultA total of 42,611 cells were identified as CD4 + T cells, CD8 + T cells, VSMC, monocytes, macrophages, fibroblasts, endothelial cells, and B cells. VSMCs were further classified into contractile VSMCs, secreting VSMCs, macrophage-like VSMCs, mesenchymal-like VSMCs, adipocyte-like VSMCs, and T-cell-like VSMCs. Intercellular communication analysis was performed between immune cells (macrophages, B cells, CD4 + T cells, CD8 + T cells) and immune related VSMCs (macrophage-like VSMCs, mesenchymal-like VSMCs, T-cell-like VSMCs, contractile VSMCs). Among selected cell populations, 27 significant signaling pathways with 61 ligand–receptor pairs were identified. Macrophages and macrophage-like VSMCs both assume the roles of a signaling sender and receiver, showing the highest communication capability. T cells acted more as senders, while B cells acted as receivers in the communication network. T-cell-like VSMCs and contractile VSMCs were used as senders, while mesenchymal-like VSMCs played a poor role in the communication network. Signaling macrophage migration inhibitory factor (MIF), galectin, and C-X-C motif chemokine ligand (CXCL) showed high information flow of intercellular communication, while signaling complement and chemerin were completely turned on in aortic aneurysms. MIF and galectin promoted VSMC switch into macrophage-like phenotypes, CXCL, and galectin promoted VSMCs transform into T-cell-like phenotypes. MIF, galectin, CXCL, complement, and chemerin all mediated the migration and recruitment of immune cells into aortic aneurysms.ConclusionThe sophisticated intercellular communication network existed between immune cells and immune-related VSMCs and changed as the aortic aneurysm progressed. Signaling MIF, galectin, CXCL, chemerin, and complement made a significant contribution to aortic aneurysm progression through activating immune cells and promoting immune cell migration, which could serve as the potential target for the treatment of aortic aneurysms.

FBLN5, a member of the short fibulins in the fibulin family of extracellular matrix/matricellular proteins, is involved in interactions with components of the basement membrane and extracellular matrix proteins. It plays key roles in endothelial tissues in many vascular diseases. In this study, the relationship between FBLN5 and carotid atherosclerotic plaque stability as well as the regulatory roles of miRNAs were evaluated. Differential gene expression analyses and weighted gene co-expression network analysis (WGCNA) based on the GSE163154 dataset (including 16 samples without intraplaque hemorrhage and 27 samples with intraplaque hemorrhage) in GEO revealed that FBLN5 is related to plaque stability and is the most significantly differentially expressed gene. LASSO regression was used to evaluate genes obtained from the intersection of differentially expressed genes and clinically significant modules identified by WGCNA. A prediction model based on eight genes, including FBLN5, was constructed and showed an accuracy of 0.951 based on an ROC analysis. Low FBLN5 expression in plaque tissues was confirmed by immunohistochemistry and western blotting. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses showed that FBLN5 acted mainly by the maintenance of the cellular matrix and reactive oxygen species production. miRNAs upstream of these eight predictive genes, including FBLN5, were identified and used to construct a network diagram. These results revealed that hsa-mir-128 and hsa-mir-532–3p were upstream regulatory factors of FBLN5, as verified by PCR assays of human plaque tissues demonstrating that both miRNAs were significantly up-regulated. Therefore, FBLN5 may play an important role in carotid atherosclerosis via hsa-mir-128 and hsa-mir-532–3p as well as become an essential target for treatment.

Abstract Background Breast cancer (BC) is a malignant tumor that occurs in the epithelial tissue of the breast gland. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) has been found to promote BC cell proliferation and invasion by regulating the microRNA (miR)-101/zinc-finger enhancer binding axis in BC. Herein, the objective of the present study is to evaluate the effect of lncRNA SNHG3 on BC cell proliferation and metastasis with the Notch signaling pathway. Methods Differentially expressed lncRNA in BC tissues and normal breast tissues was analyzed. SNHG3 si-RNA-1 and SNHG3 si-RNA-2 were constructed to detect the mechanism of SNHG3 interference in BC cell proliferation, viability, migration and invasion. Then, dual-luciferase reporter gene assay was utilized to verify the binding relation between SNHG3 and miR-154-3p as well as miR-154-3p and Notch2. Moreover, xenograft transplantation was applied to confirm the in vitro experiments. Results Highly expressed SNHG3 was observed in BC tissues. The growth of BC cells in vivo and in vitro was evidently repressed after silencing SNHG3. BC cell invasion and migration were inhibited by silencing SNHG3 in vitro. SNHG3 could act as a competing endogenous RNA of miR-154-3p and upregulate the Notch signaling pathway to promote BC cell development. Activation of the Notch signaling pathway can partly reverse the inhibition of cell activity induced by silencing SNHG3. Conclusion Our study demonstrated that interfered lncRNA SNHG3 promoted BC cell proliferation and metastasis by activating the Notch signaling pathway. This investigation may offer new insight for BC treatment.

Necroptosis is a form of programmed cell death that has recently been shown to be important in the progression of head and neck cancer (HNC). Noncoding RNAs (ncRNAs) are known to function in cell death and tumor formation. In this study, we focused on microRNAs (miRNA) that play roles in necroptosis and the progression of HNC. We collected miRNA expression data, related clinical data of patients with HNC, and miRNA data related to necroptosis. A prognostic multimiRNA molecular marker was generated based on differential expression analysis and univariate and multivariate Cox regression analyses. Target genes of the prognosis-related miRNAs were identified, and their functions were evaluated by Gene Ontology Enrichment Analysis to reveal the processes the miRNAs may be involved in. Eight potentially prognostic miRNAs were identified through differential expression analysis: miR-331-3p, miR-181d-5p, miR-181b-5p, miR-500a-3p, miR-425-5p, miR-181a-5p, miR-141-3p, and miR-200a-5p. Multivariate Cox regression identified the risk score as an independent prognostic factor (univariate Cox regression results: hazard ratio (HR): 2.2028, 95% confidence interval (CI): 1.2640–3.8388, P=0.0053; multivariate Cox regression results: HR: 2.4168, 95% CI: 1.3743–4.2501, P=0.0022). Survival curve analysis revealed that patients with a high risk score had a bad prognosis (P=0.0109). A receiver operating characteristic curve showed that the model has a certain prediction ability. We identified 187 miRNA-related genes, which were enriched in “cell cycle” and “cellular senescence.” In conclusion, this study identified eight novel miRNA markers for predicting the prognosis of patients with HNC and paved the way for future research on necroptosis-related genes.

Atherosclerosis of femoral arteries can cause the insufficient blood supply to the lower limbs and lead to gangrenous ulcers and other symptoms. Atherosclerosis and inflammatory factors are significantly different from other plaques. Therefore, it is crucial to observe the cellular composition of the femoral atherosclerotic plaque and identify plaque heterogeneity in other arteries. To this end, we performed single-cell sequencing of a human femoral artery plaque. We identified 14 cell types, including endothelial cells, smooth muscle cells, monocytes, three macrophages with four different subtypes of foam cells, three T cells, natural killer cells, and B cells. We then downloaded single-cell sequencing data of carotid atherosclerosis from GEO, which were compared with the one femoral sample. We identified similar cell types, but the femoral artery had significantly more nonspecific immune cells and fewer specific immune cells than the carotid artery. We further compared the differences in the proportion of inflammatory macrophages, and resident macrophages, and the proportion of inflammatory macrophages was greater within the carotid artery. Through comparing one femoral sequencing sample with carotid samples from public datasets, our study reveals the single-cell map of the femoral artery and the heterogeneity of carotid and femoral arteries at the cellular level, laying the foundation for mechanistic and pharmacological studies of the femoral artery.

In recent years, the vital role of genetic factors in human diseases have been widely recognized by scholars with the deepening of life science research, accompanied by the rapid development of gene-editing technology. In early years, scientists used homologous recombination technology to establish gene knock-out and gene knock-in animal models, and then appeared the second-generation gene-editing technology zinc-finger nucleases (ZFNs) and transcription activator–like effector nucleases (TALENs) that relied on nucleic acid binding proteins and endonucleases and the third-generation gene-editing technology that functioned through protein–nucleic acids complexes—CRISPR/Cas9 system. This holds another promise for refractory diseases and genetic diseases. Cardiovascular disease (CVD) has always been the focus of clinical and basic research because of its high incidence and high disability rate, which seriously affects the long-term survival and quality of life of patients. Because some inherited cardiovascular diseases do not respond well to drug and surgical treatment, researchers are trying to use rapidly developing genetic techniques to develop initial attempts. However, significant obstacles to clinical application of gene therapy still exists, such as insufficient understanding of the nature of cardiovascular disease, limitations of genetic technology, or ethical concerns. This review mainly introduces the types and mechanisms of gene-editing techniques, ethical concerns of gene therapy, the application of gene therapy in atherosclerosis and inheritable cardiovascular diseases, in-stent restenosis, and delivering systems.

Natural killer (NK) cells are an important component of the immune response to influenza infection, but are subject to alteration during aging, which may play a role in impaired response to infection and vaccination in older people. Enhancement of NK cell activity could, therefore, present a means to improve the immune response to vaccination in older subjects, and pre- and probiotics offer an opportunity to modulate antiviral defenses via alteration of the gut microbiota. This study investigated the effect of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52486, combined with a prebiotic, gluco-oligosaccharide (B. longum + Gl-OS), on the NK cell response to seasonal influenza vaccination in young and older subjects in a double-blind, randomized controlled trial. There were significant effects of aging on NK cell phenotype, the most notable of which were an increase in CD56dim cells, mainly reflected in the CD16+ subset, a decrease in CD56bright cells, mainly reflected in the CD16− subset, and greater expression of the immunosenescence marker, CD57, on NK cell subsets. However, these changes only partially translated to differences in NK cell activity, observed as trends toward reduced NK cell activity in older subjects when analyzed on a per cell basis. Influenza vaccination increased the proportion of CD56bright cells and decreased the proportion of CD56dim cells, in young, but not older subjects. Although NK cell activity in response to vaccination was not significantly different between the young and older subjects, low post-vaccination NK cell activity was associated with poor seroconversion in only the older subjects. There was no influence of the synbiotic on NK cell phenotype or activity, either before or after influenza vaccination. In conclusion, aging is associated with marked alteration of the phenotype of the NK cell population and there was evidence of an impaired NK cell response to influenza vaccination in older subjects. The effects of aging on NK cell phenotype and activity could not be offset by B. longum + Gl-OS.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT01066377.

Hypersensitivity to radiation exposure has been suggested to be a risk factor for the development of several malignancies, but not including gastric cancer. In this case-control study, radiation sensitivity as measured by chromatid breaks per cell (b/c) was examined in cultured peripheral blood lymphocytes (PBLs) from 517 patients with gastric cancer and 525 healthy controls. Our results showed that b/c values were significantly higher in cases than in controls (Mean [SD], 0.47 [0.20] vs. 0.34 [0.17]; P

Background. As a classic prescription in Chinese medicine treatment, Xiaochaihutang (XCHT) can improve the clinical effect and reduce serum tumor markers in patients with breast cancer (BC). However, there has not been any study to confirm the mechanism. We used bioinformatics analysis and network pharmacology to find the potential targets. Methods. The differentially expressed genes (DEGs) of BC were identified from the Cancer Genome Atlas (TCGA) dataset. Then, we utilized weighted coexpression network analysis (WGCNA) with the same dataset. The target genes of BC were obtained by comparing genes of DEGs and in significant modules of WGCNA. Drug targets of XCHT from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database were intersected with the targets of BC. The protein-protein interaction (PPI) of the drug targets was analysed by using the STRING database. We utilized the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analysis (KEGG) enrichment analysis to identify the specific pathways and key target proteins. Receiver operator characteristic (ROC) curve was used as the verification of drug targets. Molecular docking was performed to visualize the patterns of interactions between the effective molecule and targeted protein. Results. We obtained a set of 21 target genes, which mainly encode neurotransmitter receptors or related transporters, such as OPRD1, 5-HT2A, and so on. In addition, enrichment analyses of 21 target genes showed that they were mainly concentrated in pathways related to the nervous system. Molecular docking was performed on the target gene of BC. Six active compounds can enter the active pocket of target gene, namely, naringenin, beta-sitosterol, coumestrol, nuciferine, beta-sitosterol, and protopine, thereby exerting potential therapeutic effects in BC. Conclusions. Our analysis shows that the mechanism of XCHT in the treatment of BC is mainly acting on the neurogenesis in the microenvironment of breast tumor tissue. [ABSTRACT FROM AUTHOR]

Background: Prospective cohort studies show that higher dietary fiber intake is associated with reduced cardiovascular disease risk, yet the impact on postprandial glucose and insulin responses is unclear.Objective: This study aims to evaluate the effects of orange beverages with differing fiber concentrations on postprandial glycemic responses (secondary outcome measure) after a sequential breakfast and lunch challenge in men with increased cardiometabolic risk.Methods: Thirty-six men (aged 30-65 y; body mass index 25-30 kg/m(2): fasting triacylglycerol or total cholesterol concentrations: 0.8-2.2 or 6.0-8.0 mmol/L, respectively) were provided with a high-fat mixed breakfast and were randomly assigned to consume 240 mL Tropicana (PepsiCo, Inc.) pure premium orange juice without pulp (OJ), OJ with 5.5 g added orange pomace fiber (OPF), juice made from lightly blended whole orange, or an isocaloric sugar-matched control (Control) on 4 occasions separated by 2 wk. A medium-fat mixed lunch was provided at 330 min. Blood samples were collected before breakfast and on 11 subsequent occasions for 420 min (3 time points postlunch) to determine postprandial glucose, insulin, lipid, and inflammatory biomarker responses. Repeated-measures ANOVA was used for data analysis.Results: OPF significantly (P < 0.05) reduced the maximal change in glucose concentrations (1.9 ± 0.21 mmol/L) reached after breakfast compared with other treatments (2.3-2.4 mmol/L) and after lunch (3.0 ± 0.05 mmol/L) compared with OJ (3.6 ± 0.05 mmol/L). The maximal change in insulin concentration (313 ± 25 pmol/L) was also lower compared with Control (387 ± 30 pmol/L) and OJ (418 ± 39 pmol/L) after breakfast. OPF significantly delayed the time to reach the peak glucose concentration compared with Control and OJ, and of insulin compared with Control after breakfast.Conclusion: OPF consumed with breakfast may lower postprandial glycemic and insulinemic responses to typical meal ingestion in men with increased cardiometabolic risk. This trial is registered at clinicaltrials.gov as NCT01963416. [ABSTRACT FROM AUTHOR]

Background: Ageing increases risk of respiratory infections and impairs the response to influenza vaccination. Pre- and probiotics offer an opportunity to modulate anti-viral defenses and the response to vaccination via alteration of the gut microbiota. This study investigated the effect of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52,486, combined with a prebiotic, gluco-oligosaccharide (B. longum + Gl-OS), on the response to seasonal influenza vaccination in young and older subjects in a double-blind, randomized controlled trial, taking into account the influence of immunosenescence markers at baseline. Results: Vaccination resulted in a significant increase in total antibody titres, vaccine-specific IgA, IgM and IgG and seroprotection to all three subunits of the vaccine in both young and older subjects, and in general, the increases in young subjects were greater. There was little effect of the synbiotic, although it tended to reduce seroconversion to the Brisbane subunit of the vaccine and the vaccine-specific IgG response in older subjects. Immunological characterization revealed that older subjects randomized to the synbiotic had a significantly higher number of senescent (CD28 CD57+) helper T cells at baseline compared with those randomized to the placebo, and they also had significantly higher plasma levels of anti-CMV IgG and a greater tendency for CMV seropositivity. Moreover, higher numbers of CD28 CD57+ helper T cells were associated with failure to seroconvert to Brisbane, strongly suggesting that the subjects randomized to the synbiotic were already at a significant disadvantage in terms of likely ability to respond to the vaccine compared with those randomized to the placebo. Conclusions: Ageing was associated with marked impairment of the antibody response to influenza vaccination in older subjects and the synbiotic failed to reverse this impairment. However, the older subjects randomized to the synbiotic were at a significant disadvantage due to a greater degree of immunosenscence at baseline compared with those randomized to the placebo. Thus, baseline differences in immunosenescence between the randomized groups are likely to have influenced the outcome of the intervention, highlighting the need for detailed immunological characterization of subjects prior to interventions. Trial registration: Clinicaltrials.gov NCT01066377. [ABSTRACT FROM AUTHOR]

Background: Chemotherapeutic resistance is a main problem in clinical breast cancer therapy. The purpose of our study is to investigate whether the combination of neoadjuvant chemotherapy and survivin siRNA treatment could enhance the therapeutic effect of neoadjuvant chemotherapy using paclitaxel or epirubicin.Materials and Methods: The molecular cloning technique was applied to construct the expression vector of siRNA against survivin. Effectene Transfection Reagent was used to transfect plasmids to MCF-7 cells. Survivin expressions were detected by quantitative real-time PCR (qRT-PCR) and Western blot methods. The effect of paclitaxel or epirubicin, with or without the combination of survivin siRNA treatment, on drug susceptibility of MCF-7 cells was detected by CCK-8 assay. MCF-7 cell apoptosis was detected by Flow Cytometry.Results: Survivin siRNA effectively inhibited the expression of Survivin RNA and protein levels (P < 0.05). Both paclitaxel and epirubicin can suppress the proliferation of MCF-7 cells and induce apoptosis to a certain degree respectively. The combination of survivin siRNA with the two chemotherapy drugs significantly enhanced both effects of the two chemotherapeutics respectively (P < 0.05).Conclusion: Survivin siRNA combined with the neoadjuvant chemotherapy can significantly enhance the sensitivity of MCF-7 cells to chemotherapeutics and cell apoptosis. This technology has important potential value in the therapeutic study of breast cancer. [ABSTRACT FROM AUTHOR]