Ovarian Cancer Diagnosis and Prognosis Based on Cell-Free DNA Methylation.

Background: Ovarian cancer stands as the deadliest malignant tumor within the female reproductive tract. As a result of the absence of effective diagnostic and monitoring markers, 75% of ovarian cancer cases are diagnosed at a late stage, leading to a mere 50% survival rate within five years. The advancement of molecular biology is essential for accurate diagnosis and treatment of ovarian cancer. Methods: A review of several randomized clinical trials, focusing on the ovarian cancer, was undertaken. The advancement of molecular biology and diagnostic methods related to accurate diagnosis and treatment of ovarian cancer were examined. Results: Liquid biopsy is an innovative method of detecting malignant tumors that has gained increasing attention over the past few years. Cell-free DNA assay-based liquid biopsies show potential in delineating tumor status heterogeneity and tracking tumor recurrence. DNA methylation influences a multitude of biological functions and diseases, especially during the initial phases of cancer. The cell-free DNA methylation profiling system has emerged as a sensitive and non-invasive technique for identifying and detecting the biological origins of cancer. It holds promise as a biomarker, enabling early screening, recurrence monitoring, and prognostic evaluation of cancer. Conclusions: This review evaluates recent advancements and challenges associated with cell-free DNA methylation analysis for the diagnosis, prognosis monitoring, and assessment of therapeutic responses in the management of ovarian cancers, aiming to offer guidance for precise diagnosis and treatment of this disease.

Ovarian cancer stands as the deadliest malignant tumor within the female reproductive tract. As a result of the absence of effective diagnostic and monitoring markers, 75% of ovarian cancer cases are diagnosed at a late stage, leading to a mere 50% survival rate within five years. Nearly 80% of advanced stages have a poor prognosis or recurrence within five years. Ovarian cancer is linked to a grim long-term prognosis attributable to its elevated mortality and recurrence rates. The advancement of molecular biology and diagnostic methods is essential for accurate diagnosis and treatment of ovarian cancer. Liquid biopsy is an innovative method of detecting malignant tumors that has gained increasing attention over the past few years. Cell-free DNA assay-based liquid biopsies show potential in delineating tumor status heterogeneity and tracking tumor recurrence. DNA methylation represents a prevalent epigenetic modification. DNA methylation influences a multitude of biological functions and diseases, especially during the initial phases of cancer. The cell-free DNA methylation profiling system has emerged as a sensitive and non-invasive technique for identifying and detecting the biological origins of cancer. This review assesses recent progress and obstacles linked to cell-free DNA methylation analysis for diagnosing, prognostic monitoring, and evaluating therapeutic responses in managing ovarian cancers.

Dose-response associations of triglyceride to high-density lipoprotein cholesterol ratio and triglyceride-glucose index with arterial stiffness risk.

BACKGROUND: The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and triglyceride-glucose (TyG) index are novel indexes for insulin resistance (IR). We aimed to evaluate associations of TG/HDL-C and TyG with arterial stiffness risk. METHODS: We enrolled 1979 participants from the Rural Chinese Cohort Study, examining arterial stiffness by brachial-ankle pulse wave velocity (baPWV). Logistic and linear regression models were employed to calculate effect estimates. For meta-analysis, we searched relevant articles from PubMed, Embase and Web of Science up to August 26, 2023. The fixed-effects or random-effects models were used to calculate the pooled estimates. We evaluated dose-response associations using restricted cubic splines. RESULTS: For cross-sectional studies, the adjusted ORs (95%CIs) for arterial stiffness were 1.12 (1.01-1.23) and 1.78 (1.38-2.30) for per 1 unit increment in TG/HDL-C and TyG. In the meta-analysis, the pooled ORs (95% CIs) were 1.26 (1.14-1.39) and 1.57 (1.36-1.82) for per 1 unit increment of TG/HDL-C and TyG. Additionally, both TG/HDL-C and TyG were positively related to PWV, with ß of 0.09 (95% CI 0.04-0.14) and 0.57 (95% CI 0.35-0.78) m/s. We also found linear associations of TG/HDL-C and TyG with arterial stiffness risk. CONCLUSIONS: High TG/HDL-C and TyG were related to increased arterial stiffness risk, indicating TG/HDL-C and TyG may be convincing predictors of arterial stiffness.

PCNet: Prior Category Network for CT Universal Segmentation Model.

Accurate segmentation of anatomical structures in Computed Tomography (CT) images is crucial for clinical diagnosis, treatment planning, and disease monitoring. The present deep learning segmentation methods are hindered by factors such as data scale and model size. Inspired by how doctors identify tissues, we propose a novel approach, the Prior Category Network (PCNet), that boosts segmentation performance by leveraging prior knowledge between different categories of anatomical structures. Our PCNet comprises three key components: prior category prompt (PCP), hierarchy category system (HCS), and hierarchy category loss (HCL). PCP utilizes Contrastive Language-Image Pretraining (CLIP), along with attention modules, to systematically define the relationships between anatomical categories as identified by clinicians. HCS guides the segmentation model in distinguishing between specific organs, anatomical structures, and functional systems through hierarchical relationships. HCL serves as a consistency constraint, fortifying the directional guidance provided by HCS to enhance the segmentation model's accuracy and robustness. We conducted extensive experiments to validate the effectiveness of our approach, and the results indicate that PCNet can generate a high-performance, universal model for CT segmentation. The PCNet framework also demonstrates a significant transferability on multiple downstream tasks. The ablation experiments show that the methodology employed in constructing the HCS is of critical importance. The prompt and HCS can be accessed at https://github.com/YixinChen-AI/PCNet.

Light-Chain Cardiac Amyloidosis: Cardiac Magnetic Resonance for Assessing Response to Chemotherapy.

OBJECTIVE: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with light-chain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. MATERIALS AND METHODS: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49-63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At follow-up after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. RESULTS: Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%-1.1%] vs. 1.7% [-5.5%-7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%-1.3%] vs. 2.0% [-3.0%-5.0%]; P = 0.01) compared with those with inferior response. CONCLUSION: Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.

Olive oil intake and cardiovascular disease, cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective cohort studies.

Background: Currently, the reported links between olive oil intake and cardiovascular disease (CVD), cancer morbidity and mortality, and all-cause mortality are inconsistent. The aim of this meta-analysis is to study the reported correlations of olive oil intake with CVD, coronary heart disease (CHD), stroke and cancer incidence and mortality, and all-cause mortality. Methods: PubMed, Embase, and Web of Science were searched until March 7, 2024. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated by the random-effects model. Nonlinear dose-response relationships were modeled with restricted cubic splines. This study has been registered at PROSPERO (CRD42023419001). Results: Overall, 30 articles covering 2 710 351 participants were identified. Higher olive oil intake was linked with a reduced risk of CVD incidence (RR: 0.85; 95% CI: 0.77, 0.93), CHD incidence (RR: 0.85; 95% CI: 0.72, 0.99), CVD mortality (RR: 0.77; 95% CI: 0.67, 0.88), and all-cause mortality (RR: 0.85; 95% CI: 0.81, 0.89). For a 10 g d-1 increment of olive oil intake, the risk of CVD incidence, stroke incidence, CVD mortality, and all-cause mortality decreased by 7%, 5%, 8%, and 8%, respectively. No association was found between olive oil intake and cancer incidence and mortality. Nonlinear relationships between olive oil intake and CVD and all-cause mortality were observed, with a reduced risk from intakes ranging from 0 to 18 g d-1 and 0 to 22 g d-1, respectively. Conclusion: Our study found that high olive oil intake was related to a lower risk of CVD and CHD incidence and CVD mortality and all-cause mortality.

Visit to visit transition in TXNIP gene methylation and the risk of type 2 diabetes mellitus: a nested case-control study.

Our study aimed to investigate the association between the transition of the TXNIP gene methylation level and the risk of incident type 2 diabetes mellitus (T2DM). This study included 263 incident cases of T2DM and 263 matched non-T2DM participants. According to the methylation levels of five loci (CpG1-5; chr1:145441102-145442001) on the TXNIP gene, the participants were classified into four transition groups: maintained low, low to high, high to low, and maintained high methylation levels. Compared with individuals whose methylation level of CpG2-5 at the TXNIP gene was maintained low, individuals with maintained high methylation levels showed a 61-87% reduction in T2DM risk (66% for CpG2 [OR: 0.34, 95% CI: 0.14, 0.80]; 77% for CpG3 [OR: 0.23, 95% CI: 0.07, 0.78]; 87% for CpG4 [OR: 0.13, 95% CI: 0.03, 0.56]; and 61% for CpG5 [OR: 0.39, 95% CI: 0.16, 0.92]). Maintained high methylation levels of four loci of the TXNIP gene are associated with a reduction of T2DM incident risk in the current study. Our study suggests that preserving hypermethylation levels of the TXNIP gene may hold promise as a potential preventive measure against the onset of T2DM.

The S-acylation cycle of transcription factor MtNAC80 influences cold stress responses in Medicago truncatula.

S-acylation is a reversible post-translational modification catalyzed by protein S-acyltransferases (PATs), and acyl protein thioesterases (APTs) mediate de-S-acylation. Although many proteins are S-acylated, how the S-acylation cycle modulates specific biological functions in plants is poorly understood. In this study, we report that the S-acylation cycle of transcription factor MtNAC80 is involved in the Medicago truncatula cold stress response. Under normal conditions, MtNAC80 localized to membranes through MtPAT9-induced S-acylation. In contrast, under cold stress conditions, MtNAC80 translocated to the nucleus through de-S-acylation mediated by thioesterases such as MtAPT1. MtNAC80 functions in the nucleus by directly binding the promoter of the glutathione S-transferase gene MtGSTU1 and promoting its expression, which enables plants to survive under cold stress by removing excess malondialdehyde and H2O2. Our findings reveal an important function of the S-acylation cycle in plants and provide insight into stress response and tolerance mechanisms.

Miscarriage and stillbirth in relation to risk of cardiovascular diseases: A systematic review and meta-analysis.

INTRODUCTION: The relationship between pregnancy loss and the risk of cardiovascular diseases (CVDs) remains a matter of debate. Our intention in conducting this meta-analysis was to analyze the relationship between miscarriage and stillbirth and risk of CVDs. METHODS: PubMed, Embase, and Web of Science were systematically searched up to May 30, 2023 for all relevant studies. The random-effects model was applied to estimate the pooled relative risks (RRs) and 95% confidence intervals (95% CIs). We evaluated RR estimates for the risk of CVDs with each additional miscarriage and stillbirth through generalized least squares regression. RESULTS: Twenty-three articles were incorporated into the meta-analysis. For women with a history of miscarriage, the pooled RRs for the risk of total CVDs, coronary heart disease (CHD), stroke, and total CVD deaths were 1.16 (95 % CI 1.10-1.22), 1.26 (1.12-1.41), 1.13 (1.03-1.24), and 1.20 (1.01-1.42), respectively. For women with a history of stillbirth, the pooled RRs for the risk of total CVDs, CHD, stroke, and total CVD deaths were 1.60 (1.34-1.89), 1.30 (1.12-1.50), 1.37 (1.06-1.78), and 1.95 (1.05-3.63), respectively. With each additional miscarriage, the risk increased for total CVDs (1.08, 1.04-1.13), CHD (1.08, 1.04-1.13), and stroke (1.05, 1.00-1.10). With each additional stillbirth, the risk increased for total CVDs (1.11, 1.03-1.21) and CHD (1.13, 1.07-1.19). CONCLUSION: This meta-analysis indicates that both miscarriages and stillbirths are related to a higher risk of total CVDs, CHD, stroke, and total CVD deaths. The risk of total CVDs and CHD increased with the number of miscarriages or stillbirths.

Denitrification Characteristics of the Low-Temperature Tolerant Denitrification Strain Achromobacter spiritinus HS2 and Its Application.

The low-temperature environment significantly inhibits the growth and metabolism of denitrifying bacteria, leading to an excessive concentration of ammonia nitrogen and total nitrogen in sewage treatment plants during the cold season. In this study, an efficient denitrifying strain of heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria named HS2 was isolated and screened from industrial sewage of a chemical factory in Inner Mongolia at 8 °C. The strain was confirmed to be Achromobacter spiritinus, a colorless rod-shaped bacterium. When cultured with sodium succinate as the carbon source, a carbon-to-nitrogen ratio of 20-30, a shaking rate of 150-180 r/min, and an initial pH of 6-10, the strain HS2 exhibited excellent nitrogen removal at 8 °C. Through the results of whole-genome sequencing, gene amplification, and gas product detection, the strain HS2 was determined to possess key enzyme genes in both nitrification and denitrification pathways, suggesting a HN-AD pathway of NH4+-N → NH2OH → NO2-N → NO → N2O → N2. At 8 °C, the strain HS2 could completely remove ammonia nitrogen from industrial sewage with an initial concentration of 127.23 mg/L. Microbial species diversity analysis of the final sewage confirmed Achromobacter sp. as the dominant genus, which indicated that the low-temperature denitrifying strain HS2 plays an important role in nitrogen removal in actual low-temperature sewage.

Efficacy and safety of daratumumab plus bortezomib and dexamethasone in newly diagnosed Mayo 2004 stage IIIA or IIIB light-chain amyloidosis: a prospective phase II study.

Not available.

Obesity and risk of depressive disorder in children and adolescents: A meta-analysis of observational studies.

PURPOSE: This meta-analysis evaluated the relationship between overweight/obesity and depressive disorders in children and adolescents. METHODS: We examined the databases of PubMed, Embase and Web of Science for pertinent observational studies released up until 20 February 2022. The pooled relative risks (RRs) and 95% confidence intervals (CIs) of obesity and overweight with depressive disorder were calculated by means of random-effects models. The Newcastle-Ottawa Quality Assessment Scale and Agency for Healthcare Research and Quality scale were adopted to evaluate the study quality. RESULTS: Finally, for this meta-analysis, we evaluated 22 observational publications covering 175 135 participants (5 cohort study articles, 1 case-control study article and 16 cross-sectional study articles). A significant positive association was found between obesity and the risk of depression (RR 1.32, 95% CI 1.09-1.60, I2 = 79.90%, Pheterogeneity < 0.001) and in the association between obesity and depressive symptoms (RR 1.16, 95% CI: 1.00-1.35, I2 = 25.0%, Pheterogeneity = 0.247). On sensitivity analysis, the pooled RRs remained robust. Subgroup analysis indicated that obese children and teenagers in western countries were more prone to depression. CONCLUSION: Evidence from this meta-analysis, based on observational studies, supported the idea that obese children and adolescents are more likely to experience depression and depressive symptoms.

UBES: Unified scatter correction using ultrafast Boltzmann equation solver for conebeam CT.

A semi-analytical solution to the unified Boltzmann equation is constructed to exactly describe the scatter distribution on a flat-panel detector for high-quality conebeam CT (CBCT) imaging. The solver consists of three parts, including the phase space distribution estimator, the effective source constructor and the detector signal extractor. Instead of the tedious Monte Carlo solution, the derived Boltzmann equation solver achieves ultrafast computational capability for scatter signal estimation by combining direct analytical derivation and time-efficient one-dimensional numerical integration over the trajectory along each momentum of the photon phase space distribution. The execution of scatter estimation using the proposed ultrafast Boltzmann equation solver (UBES) for a single projection is finalized in around 0.4 seconds. We compare the performance of the proposed method with the state-of-the-art schemes, including a time-expensive Monte Carlo (MC) method and a conventional kernel-based algorithm using the same dataset, which is acquired from the CBCT scans of a head phantom and an abdominal patient. The evaluation results demonstrate that the proposed UBES method achieves comparable correction accuracy compared with the MC method, while exhibits significant improvements in image quality over learning and kernel-based methods. With the advantages of MC equivalent quality and superfast computational efficiency, the UBES method has the potential to become a standard solution to scatter correction in high-quality CBCT reconstruction.

Association of methylation risk score with incident type 2 diabetes mellitus: A nested case-control study.

AIMS: To investigate the association of methylation risk score (MRS) and its interactions with environmental factors with type 2 diabetes mellitus (T2DM) risk. METHODS: We conducted a nested case-control study with 241 onset cases and 241 matched controls. Conditional logistic regression models were employed to identify risk CpG sites. Simple and weighted MRSs were constructed based on the methylation levels of ATP-binding cassette G1 gene, fat mass and obesity associated gene, potassium voltage-gated channel member 1 gene, and thioredoxin-interacting protein gene previously associated with T2DM to estimate the association of MRS with T2DM risk. Stratified analyses were used to investigate interactions between MRS and environmental factors. RESULTS: A total of 10 CpG loci were identified from the aforementioned genes to calculate MRS. After controlling for potential confounding factors, taking tertile 1 as reference, the odds ratios (ORs) and 95% confidence intervals (CIs) for T2DM of tertile 3 was 2.39 (1.36-4.20) for simple MRS and 2.59 (1.45-4.63) for weighted MRS. With per SD score increment in MRS, the OR (95% CI) was 1.66 (1.29-2.14) and 1.60 (1.24-2.08) for simple and weighted MRSs, respectively. J-curved associations were observed between both simple and weighted MRSs and T2DM risks. Additionally, multiplication interactions for smoking and hypertension with simple MRS on the risk of T2DM were found, similarly for smoking and obesity with weighted MRS on the risk of T2DM (all Pinteraction < .05). CONCLUSION: Elevated simple and weighted MRSs were associated with increased risk of T2DM. Environmental risk factors may influence the association between MRS and T2DM.

KISS-1 knockdown inhibits cell growth, migration, and invasion in HTR-8/SVneo cells by regulating the GRP54-mediated PI3K/AKT signaling pathway.

Recurrent spontaneous abortions (RSA) affect reproductive health and increase the risk of subsequent abortions. To investigate the role of KISS-1/GPR-54 signaling in RSA progression. Villus tissue was collected from RSA patients, and human trophoblastic HTR-8/SVneo cells were used. KISS-1 and GRP54 levels were detected using RT-qPCR and immunohistochemistry. Western blotting was performed to analyze ZO-1 and ZEB1 levels. Cell proliferation was determined via CCK-8 and cell clone formation assays. Transwell assays were performed to assess cell migration and invasion abilities. KISS-1 was down-regulated in the villus tissues of RSA patients. KISS-1 overexpression dramatically inhibited trophoblast proliferation, migration, and invasion. Mechanistically, ZEB1 expression was down-regulated, whereas ZO-1 expression was up-regulated, after KISS-1 overexpression. GPR54 silencing neutralized the effect of KISS-1 in HTR-8/SVneo cells. Additionally, KISS-1 overexpression inactivated the PI3K/AKT signaling pathway through GRP54. The KISS-1/GPR-54 signaling axis regulates RSA progression by regulating the PI3K/AKT signaling pathway.

BGB-A445, a novel non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical models.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.

Developing Chinese university students' academic literacies in English language classrooms via a production-oriented approach: an action research perspective.

Developing academic literacies is becoming an important research topic in TESOL and has received increasing scholarly attention. One of the difficulties in developing university students' academic literacy in English language speaking is the lack of an authentic English language learning environment and the way to help students more effectively develop their language competence. To address this issue, this study seeks to explore the academic literacy development of 24 non-English major students in an 8-week-long integrated English class at a Chinese university from late 2022 to early 2023. Based on a production-oriented approach (POA) action research design, this study follows the typical framework of driving, enabling, and assessing phases to chain together the teaching and learning actions. Quantitative data from questionnaires were analyzed via SPSS software, whereas thematic analysis and content analysis were adopted in examining the qualitative data including classroom observations, teacher reflection journals, and semi-structured interviews. Based on our data analysis, this study finds that POA can have a positive effect on improving students' participation, performance, and task completion, which improves their academic literacies. Implications on how POA helps in facilitating EFL students' academic literacies development are discussed along with the acquisition model and future research directions like students' identity issues and teachers' perceptions of pedagogical approaches in teaching academic literacy within university settings.

Long-Term Exposure to Traffic Noise and Risk of Incident Cardiovascular Diseases: a Systematic Review and Dose-Response Meta-Analysis.

While noise pollution from transportation has become an important public health problem, the relationships between different sources of traffic noise and cardiovascular diseases (CVDs) remain inconclusive. A comprehensive meta-analysis was therefore conducted to quantitatively assess the effects of long-term exposure to road traffic, railway, and aircraft noise on CVDs and relevant subtypes. We systematically retrieved PubMed, Embase, and Web of Science for articles published before April 4, 2022. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated by the fixed- or random-effects models. In total, 23 articles were included in our meta-analysis. The risk of CVDs increased by 2% (RR 1.020, 95% CI 1.006-1.035) and 1.6% (RR 1.016, 95% CI 1.000-1.032) for every 10 dB increment of road traffic and aircraft noise. For CVD subtypes, the risk increased by 3.4% (1.034, 1.026-1.043) for stroke and 5% (1.050, 1.006-1.096) for heart failure with each 10 dB increment of road traffic noise; the risk of atrial fibrillation increased by 1.1% (1.011, 1.002-1.021) with each 10 dB increment of railway noise; and the risk increased by 1% (1.010, 1.003-1.017) for myocardial infarction, 2.7% (1.027, 1.004-1.050) for atrial fibrillation, and 2.3% (1.023, 1.016-1.030) for heart failure with each 10 dB increment in aircraft noise. Further, effects from road traffic, railway, and aircraft noise all followed positive linear trends with CVDs. Long-term exposure to traffic noise is positively related to the incidence risk of cardiovascular events, especially road traffic noise which significantly increases the risk of CVDs, stroke, and heart failure.

Lack of Rab27a attenuates foam cell formation and macrophage inflammation in uremic apolipoprotein E knockout mice.

As the most common cardiovascular disease, atherosclerosis (AS), is a leading cause of high mortality in patients with chronic renal failure. Rab27a has been reported to regulate the progression of cardiovascular and renal diseases. Nevertheless, little studies investigated the role and mechanism of Rab27a in uremic-accelerated AS (UAAS). An animal model of UAAS was established in apolipoprotein E knockout (apoE-/-) mice using 5/6 nephrectomy (NX). We conducted in vitro and in vivo functional experiments to explore the role of Rab27a in UAAS, including the presence of oxidized low-density lipoprotein (ox-LDL). Rab27a expression was upregulated in the plaque tissues of NX apoE-/- mice. The knockout of Rab27a (Rab27a-/-) reduced AS-induced artery injury, as manifested by the reductions of plaque area, collagen deposition, inflammation and lipid droplet. Besides, cholesterol efflux was increased, while the expression of lipid metabolism-related proteins and the secretions of pro-inflammatory factors were decreased in ox-LDL-induced NX Rab27a-/- apoE-/- mice group. Further, Rab27a deletion inhibited the activation of nuclear factor κB (NF-κB) pathway. In conclusion, our study indicated that Rab27a deficiency attenuated foam cell formation and macrophage inflammation, depending on the NF-κB pathway activation, to inhibit AS progression in uremic apoE-/- mice. This finding may provide a new targeting strategy for UAAS therapy.