Contribution of FOS in neutrophils to venous thromboembolism via miR-144 based on bioinformatic prediction and validation.

The Finkel-Biskis-Jinkins Osteosarcoma (c-Fos; encoded by FOS) plays an important role in several cardiovascular diseases, including atherosclerosis and stroke. However, the relationship between FOS and venous thromboembolism (VTE) remains unknown. We identified differentially expressed genes in Gene Expression Omnibus dataset, GSE48000, comprising VTE patients and healthy individuals, and analysed them using CIBERSORT and weighted co-expression network analysis (WGCNA). FOS and CD46 expressions were significantly downregulated (FOS p = 2.26E-05, CD64 p = 8.83E-05) and strongly linked to neutrophil activity in VTE. We used GSE19151 and performed PCR to confirm that FOS and CD46 had diagnostic potential for VTE; however, only FOS showed differential expression by PCR and ELISA in whole blood samples. Moreover, we found that hsa-miR-144 which regulates FOS expression was significantly upregulated in VTE. Furthermore, FOS expression was significantly downregulated in neutrophils of VTE patients (p = 0.03). RNA sequencing performed on whole blood samples of VTE patients showed that FOS exerted its effects in VTE via the leptin-mediated adipokine signalling pathway. Our results suggest that FOS and related genes or proteins can outperform traditional clinical markers and may be used as diagnostic biomarkers for VTE.

Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

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.

Palladium/TY-Phos-Catalyzed Asymmetric Heck/Tsuji-Trost Reaction of o-Bromophenols with 1,3-Dienes.

2,3-Dihydrobenzofurans are crucial building blocks in the synthesis of natural products and pharmaceutical molecules. However, their asymmetric synthesis has been a long-standing formidable challenge so far. In this work, we developed a highly enantioselective Pd/TY-Phos-catalyzed Heck/Tsuji-Trost reaction of o-bromophenols with various 1,3-dienes, allowing expedient access to chiral substituted 2,3-dihydrobenzofurans. This reaction features excellent regio- and enantiocontrol, high functional group tolerance, and easy scalability. More importantly, the demonstration of this method as a highly valuable tool for the construction of optically pure natural products (R)-tremetone and fomannoxin is highlighted.

Single-cell RNA sequencing reveals the vascular smooth muscle cell phenotypic landscape in aortic aneurysm.

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.

Fluoroquinolones increase susceptibility to aortic aneurysm and aortic dissection: Molecular mechanism and clinical evidence.

Aortic aneurysm (AA) and aortic dissection (AD) are prevalent severe cardiovascular diseases that result in catastrophic complications and unexpected deaths. Owing to the lack of clinically established and effective medications, the only treatment options are open surgical repair or endovascular therapy. Most researchers have focused on the development of innovative medications or therapeutic targets to slow the progression of AA/AD or lower the risk of malignant consequences. Recent studies have shown that the use of fluoroquinolones (FQs) may increase susceptibility to AA/AD to some extent, especially in patients with aortic dilatation and those at a high risk of AD. Therefore, it is crucial for doctors, particularly those in cardiovascular specialties, to recognize the dangers of FQs and adopt alternatives. In the present review, the main clinical observational studies on the correlation between FQs and AA/AD in recent years are summarized, with an emphasis on the relative physiopathological mechanism incorporating destruction of the extracellular matrix (ECM), phenotypic transformation of vascular smooth muscle cells, and local inflammation. Although additional data are required, it is anticipated that the rational use of FQs will become the standard of care for the treatment of aortic diseases.

Safety and Efficacy of the Passeo-18 Lux Drug-Coated Balloon Catheter in Atherosclerotic Femoropopliteal Lesions: The Multicenter BIOLUX P-IV China Study.

BACKGROUND: The purpose of this trial was to assess the safety and effectiveness of a paclitaxel-coated balloon catheter in Chinese patients with de novo or nonstented restenotic femoropopliteal atherosclerotic lesions. METHODS: BIOLUX P-IV China is a prospective, independently adjudicated, multicenter, single-arm trial conducted in China. Patients with Rutherford class 2-4 were eligible, excluded were patients in which predilation resulted in severe (≥ grade D) flow-limiting dissection or residual stenosis > 70%. Follow-up assessments were conducted at 1, 6, and 12 months. The primary safety end point was 30-day major adverse event rate and the primary effectiveness end point was primary patency at 12 months. RESULTS: We enrolled 158 patients with 158 lesions. Mean age was 67.6 ± 9.6 years, diabetes was present in 53.8% (n = 85), and previous peripheral intervention/surgeries in 17.1% (n = 27). Lesions were 4.1 ± 0.9 mm in diameter and 74 ± 50 mm long with a mean diameter stenosis of 91 ± 13%; 58.2% (n = 92) were occluded (core laboratory analysis). Device success was achieved in all patients. The rate of major adverse events was 0.6% (95% confidence interval: 0.0; 3.5) at 30 days, consisting of 1 target lesion revascularization. At 12 months, binary restenosis was present in 18.7% (n = 26) and target lesion revascularization was performed in 1.4% (n = 2, all clinically driven), resulting in a primary patency of 80.0% (95% confidence interval: 72.4, 85.8); no major target limb amputation occurred. Clinical improvement at 12 months, defined as improvement of at least 1 Rutherford class, was 95.3% (n = 130). The median walking distance per 6-minute walk test was 279 m at baseline and improved by 50 m at 30 days and by 60 m at 12 months; the visual analogue scale changed from 76.6 ± 15.6 at baseline to 80.0 ± 15.0 at 30 days and 78.6 ± 14.6 at 12 months. CONCLUSIONS: Our results confirmed the clinical effectiveness and safety of a paclitaxel-coated peripheral balloon dilatation catheter for the treatment of de novo and nonstented restenotic lesion of the superficial femoral and proximal popliteal artery in Chinese patients (NCT02912715).

The intellectual base and global trends in contrast-induced acute kidney injury: a bibliometric analysis.

Contrast-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.

How vascular smooth muscle cell phenotype switching contributes to vascular disease.

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.

Long non-coding RNA SNHG3 promotes breast cancer cell proliferation and metastasis by binding to microRNA-154-3p and activating the notch signaling pathway.

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.

Urinary fibrinogen is elevated in hospitalized patients undergoing angiography.

OBJECTIVES: Previously, we found that urinary fibrinogen (Fg) levels were positively related to contrast-induced acute renal injury degree in mice. Reduction of fibrinogen in heterozygous mice can improve renal function. Here, we prospectively observed the variation in urinary Fg levels in patients undergoing angiography to determine the relationship between serum creatinine (Scr) and serum cystatin C (Cys C) levels. METHODS: Serum Cys C and urinary Fg levels were evaluated by ELISA before and 2, 12, and 24 h after angiography in 115 enrolled inpatients. Scr was assessed before and 24 and 48 h after angiography. Data were analyzed using ANOVA or Kruskal-Wallis ANOVA and Spearman correlation. RESULTS: Urinary Fg levels were elevated as early as 2 h after angiography and decreased thereafter before returning to baseline levels 24 h after angiography. Urinary Fg was correlated with the amount of contrast agent ( r = 0.24, p = 0.036) and the presence of diabetes and hypertension ( r = 0.31, r = 0.28, p < 0.05, respectively). Urinary Fg levels 2 h after angiography were positively related with Cys C at 12 and 24 h and Scr at 48 h after angiography ( r = 0.34, r = 0.51, r = 0.85, p < 0.05, respectively). CONCLUSIONS: Our results showed that variations in urinary Fg levels are consistent with serum Cys C and Scr in patients undergoing angiography and that urinary Fg levels were the earliest parameter to become elevated. Urinary Fg should be investigated as a useful predictor for abnormal renal function after angiography.

Relationship between ADAMTS4 and carotid atherosclerotic plaque vulnerability in humans.

BACKGROUND: Rupture of atherosclerotic plaques and the resulting thrombosis are vital causes of clinical ischemic events. Recent studies have shown that ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4) is a pathogenic factor of plaque vulnerability in mice. However, the relationship between ADAMTS4 and carotid atherosclerotic vulnerable plaques in humans remains unclear. METHODS: Forty-eight carotid atherosclerotic plaque specimens were obtained from 48 carotid artery stenosis inpatients undergoing carotid endarterectomy. We performed hematoxylin and eosin and Movat pentachrome staining for histologic characteristics; immunohistochemical staining for ADAMTS4, versican, and macrophages; and serologic tests for ADAMTS4. Patients were divided into stable and vulnerable groups on the basis of histologic characterization according to the classification criteria of the American Heart Association. Comparison between the groups was carried out using SPSS 17.0 (SPSS Inc, Chicago, Ill). RESULTS: Expression of ADAMTS4 in the plaque and its serum concentration were significantly higher in the vulnerable group compared with the stable one (P = .004 and P = .021, respectively), whereas the expression of versican was lower in the vulnerable group than in the stable group (P = .015). Univariate analysis revealed that the incidence of symptomatic cerebral ischemic events and ADAMTS4 serum levels were statistically higher in the vulnerable group compared with the stable group (P = .021 and P = .029, respectively). Multivariate analysis showed that ADAMTS4 was an independent risk factor (odds ratio, 1.14; P = .038). CONCLUSIONS: Our study revealed that ADAMTS4 expression was upregulated during carotid atherosclerotic plaque development. Serum levels of ADAMTS4 were associated with increased plaque vulnerability in both symptomatic and asymptomatic patients with carotid artery stenosis. ADAMTS4 may be a potential biomarker for plaque vulnerability.

Addition of Orange Pomace to Orange Juice Attenuates the Increases in Peak Glucose and Insulin Concentrations after Sequential Meal Ingestion in Men with Elevated Cardiometabolic Risk.

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.

Flavanone-rich citrus beverages counteract the transient decline in postprandial endothelial function in humans: a randomised, controlled, double-masked, cross-over intervention study.

Specific flavonoid-rich foods/beverages are reported to exert positive effects on vascular function; however, data relating to effects in the postprandial state are limited. The present study investigated the postprandial, time-dependent (0-7 h) impact of citrus flavanone intake on vascular function. An acute, randomised, controlled, double-masked, cross-over intervention study was conducted by including middle-aged healthy men (30-65 years, n 28) to assess the impact of flavanone intake (orange juice: 128·9 mg; flavanone-rich orange juice: 272·1 mg; homogenised whole orange: 452·8 mg; isoenergetic control: 0 mg flavanones) on postprandial (double meal delivering a total of 81 g of fat) endothelial function. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery at 0, 2, 5 and 7 h. Plasma levels of naringenin/hesperetin metabolites (sulphates and glucuronides) and nitric oxide species were also measured. All flavanone interventions were effective at attenuating transient impairments in FMD induced by the double meal (7 h post intake; P<0·05), but no dose-response effects were observed. The effects on FMD coincided with the peak of naringenin/hesperetin metabolites in circulation (7 h) and sustained levels of plasma nitrite. In summary, citrus flavanones are effective at counteracting the negative impact of a sequential double meal on human vascular function, potentially through the actions of flavanone metabolites on nitric oxide.

Effect of a synbiotic on the response to seasonal influenza vaccination is strongly influenced by degree of immunosenescence.

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.

Orange pomace fibre increases a composite scoring of subjective ratings of hunger and fullness in healthy adults.

Dietary fibre has been shown to increase subjective satiating ratings. However data from human trials has produced mixed results, possibly due to different types of fibre which have diverse physicochemical properties and gastrointestinal transit behaviour. The aim of study 1 was to investigate whether orange juice (OJ) with 5.5 g of added orange pomace fibre (OPF) was as satiating as whole orange (WO, chopped and blended to a puree/liquid) compared with OJ. Study 2 was to evaluate the dose-dependent satiating effect of OPF delivered in an orange-flavoured beverage. Both studies were randomized, controlled, double blind, cross over in design with 4 intervention arms in study 1 including OJ, OPF, WO, and water, and 3 arms in study 2: orange-flavoured beverage with low (2.5 g) and high (5.5 g) dose of OPF (LD-OPF and HD-OPF), and orange-flavoured beverage without fibre (Control). Volunteers were asked to response to 8 questions relating to hunger, fullness, desire to eat, thirst and discomfort by visual analogue scale (VAS) for each question. Differences were detected in least squares mean estimates of composite satiety scores and each individual question with statistical modelling to adjust for differences in baseline scores. Addition of 5.5 g OPF either to OJ or to orange-flavoured beverage significantly increased the composite satiety scores compared with OJ (P < 0.0001) or Control (P < 0.0001), and the effect was comparative to WO. LD-OPF showed some satiating effect (less desire to eat) compared with Control (P = 0.038), though less effective than HD-OPF (P = 0.043). In conclusion, the addition of OPF to OJ was as effective at increasing satiety as WO consumption compared with OJ; and there was a trend of dose-dependent effect of OPF on satiety compared with the control.

Evaluation of urine fibrinogen level in a murine model of contrast-induced nephropathy.

OBJECTIVE: The mechanisms of contrast-induced nephropathy are not fully understood and sensitive biomarkers of contrast-induced nephropathy are yet to be found. We investigated whether urinary fibrinogen could be a potential biomarker for contrast-induced nephropathy. METHODS: To create a contrast-induced nephropathy model, mice received a prostaglandin synthesis inhibitor (indomethacin) and a nitric oxide synthase inhibitor (Nω-Nitro-L-arginine methyl ester) intraperitoneally followed by a different dose of iodixanol. In the control group, normal saline was administered. Urinary fibrinogen and serum creatinine were analyzed using enzyme-linked immunosorbent assay. Kidneys were used to quantify fibrinogen using qRT-PCR and Western blot and for histopathological examination. RESULTS: Histopathological examination demonstrated mild renal injury in the low-dose group, and moderate renal injury in the high-dose group. Urinary fibrinogen levels were significantly increased in an iodixanol dose-dependent manner (control vs. low-dose group, P < 0.05; control vs. high-dose group P < 0.01). Serum creatinine levels were only increased in the high-dose group (P < 0.01 compared to control), but not in the low-dose group. For fibrinogen-gene expression, in the low-dose group, Fgγ increased (qRT-PCR, Western blot, P < 0.05) in the high-dose group, Fgß and Fgγ decreased (qRT-PCR, P < 0.01; Western blot, P < 0.05), and Fgα increased (qRT-PCR, P < 0.05; Western blot, P < 0.05). CONCLUSIONS: We propose that urinary fibrinogen could be used as a potential biomarker for early contrast-induced nephropathy diagnosis.

Effect of thymidylate synthase gene polymorphism on the response to chemotherapy and clinical outcome of non-small cell lung cancer patients.

Genetic polymorphisms of thymidylate synthase (TYMS) gene have been reported to be associated with development or prognosis of several cancers. However, the association between polymorphisms of TYMS gene and clinical outcomes of non-small cell lung cancer (NSCLC) patients are still unknown. In the present study, we investigated the associations between single nucleotide polymorphisms (SNPs) of TYMS gene and response to chemotherapy as well as clinical outcomes in NSCLC patients. Five SNPs in TYMS gene were genotyped using the Sequenom iPLEX genotyping system in a hospital-based cohort with 500 NSCLC patients, and their associations with NSCLC outcomes were evaluated by Cox proportional hazard regression analysis under three genetic models (additive, dominant, and recessive models). Our data showed that there was no significant association between individual SNP and overall survival of NSCLC patients. However, SNP rs2847153 was significantly associated with NSCLC recurrence under recessive model. We further identified a significant interaction between rs2847153 and chemotherapy in modifying clinical outcome of patients. Our data showed that individuals carrying GG/GA genotypes of rs2847153 had a significantly better response to chemotherapy when comparing to those carrying AA genotype. Conclusively, our data suggest that SNPs rs2847153 in TYMS gene may be a potential biomarker for predicting clinical outcome and personalized treatment in NSCLC patients.

External ultrasound for carotid atherosclerotic plaque treatment.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of external ultrasound in the treatment of carotid atherosclerotic plaques. METHODS: In the prospective study, 357 patients with 363 carotid atherosclerotic plaques were divided into an ultrasound treatment group and a control group. For 30 days, conventional medical treatment was conducted on 54 plaques in the control group, whereas irradiation therapy in addition to conventional medical treatment was conducted on 309 plaques in the ultrasound group. Carotid sonography was conducted before and after treatment, and the maximum plaque thickness and area were measured in a longitudinal section. RESULTS: No patients withdrew from the treatment because of related side effects. After treatment, the maximum thickness and area of 79.94% of the plaques in the ultrasound group were reduced, whereas in the control group, the thickness and area of 18.52% were reduced. The mean changes in plaque thickness and area ± SD in the ultrasound and control groups were 0.22 ± 0.19 mm (7.61% ± 5.67%) versus 0.02 ± 0.05 mm (0.74% ± 1.64%) and 0.047 ± 0.039 cm(2) (13.28% ± 9.8%) versus 0.0044 ± 0.0102 cm(2) (1.1% ± 2.46%), respectively. Changes in both plaque thickness and area in the ultrasound group were significantly greater than those in the control group (P< .0001). Furthermore, the plaque echo type was another prognostic factor affecting efficacy (P < .05). CONCLUSIONS: External ultrasound treatment is safe and effective for carotid atherosclerotic plaques and is worthy of further research and applications. The efficacy in anechoic/hypoechoic plaques is significantly higher than that in mixed echoic and calcified echoic plaques.

The Down-Shifting Luminescence of Rare-Earth Nanoparticles for Multimodal Imaging and Photothermal Therapy of Breast Cancer.

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.

Understanding the role of red blood cells in venous thromboembolism: A comprehensive review.

Traditionally, red blood cells (RBCs) have been perceived as passive entities within the fibrin network, without any significant role in the pathophysiology of venous thromboembolism (VTE). This review explores the involvement of RBCs in the VTE process, summarizing previous study findings and providing a comprehensive review of the latest theories. At first, it explores the influence of abnormal RBC counts (as seen in polycythemia vera and with erythropoietin use) and the exposure of RBCs to phosphatidylserine (Ptd-L-Ser) in the pathophysiology of VTE. The mechanisms of endothelial injury induced by RBCs and their adhesion to the endothelium under different disease models are then demonstrated. We explore the role of physical and chemical interactions between RBCs and platelets, as well as the interactions between RBCs and neutrophils - particularly the neutrophil extracellular traps (NETs) released by neutrophils - in the process of VTE. Additionally, we investigate the effect of RBCs on thrombin activation through two pathways, namely, the FXIIa-FXI-FIX pathway and the prekallikrein-dependent pathway. Lastly, we discuss the impact of RBCs on clot volume. In conclusion, we propose several potential methods aimed at unraveling the role of RBCs and their interaction with other components in the vascular system in the pathogenesis of VTE.