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Background: Cardiac rupture (CR) is a rare but catastrophic mechanical complication of acute myocardial infarction (AMI) that seriously threatens human health. However, the reliable biomarkers for clinical diagnosis and the underlying signaling pathways insights of CR has yet to be elucidated. Methods: In the present study, a quantitative approach with tandem mass tag (TMT) labeling and liquid chromatography–tandem mass spectrometry was used to characterize the differential protein expression profiles of patients with CR. Plasma samples were collected from patients with CR (n = 37), patients with AMI (n = 47), and healthy controls (n = 47). Candidate proteins were selected for validation by multiple reaction monitoring (MRM) and enzyme-linked immunosorbent assay (ELISA). Results: In total, 1208 proteins were quantified and 958 differentially expressed proteins (DEPs) were identified. The difference in the expression levels of the DEPs was more noticeable between the CR and Con groups than between the AMI and Con groups. Bioinformatics analysis showed most of the DEPs to be involved in numerous crucial biological processes and signaling pathways, such as RNA transport, ribosome, proteasome, and protein processing in the endoplasmic reticulum, as well as necroptosis and leukocyte transendothelial migration, which might play essential roles in the complex pathological processes associated with CR. MRM analysis confirmed the accuracy of the proteomic analysis results. Four proteins i.e., C-reactive protein (CRP), heat shock protein beta-1 (HSPB1), vinculin (VINC) and growth/differentiation factor 15 (GDF15), were further validated via ELISA. By receiver operating characteristic (ROC) analysis, combinations of these four proteins distinguished CR patients from AMI patients with a high area under the curve (AUC) value (0.895, 95% CI, 0.802–0.988, p < 0.001). Conclusions: Our study highlights the value of comprehensive proteomic characterization for identifying plasma proteome changes in patients with CR. This pilot study could serve as a valid foundation and initiation point for elucidation of the mechanisms of CR, which might aid in identifying effective diagnostic biomarkers in the future. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a systemic inflammatory response syndrome characterized by persistent inflammation and immunosuppression, leading to septic shock and multiple organ dysfunctions. Ubiquitin-specific peptidase 10 (USP10), a deubiquitinase enzyme, plays a vital role in cancer and arterial restenosis, but its involvement in sepsis is unknown. Objective: In this study, we investigated the significance of USP10 in lipopolysaccharide (LPS)-stimulated macrophages and its biological roles in LPS-induced sepsis. Methods: Lipopolysaccharides (LPS) were used to establish sepsis models in vivo and in vitro. We use western blot to identify USP10 expression in macrophages. Spautin-1 and USP10-siRNA were utilized for USP10 inhibition. ELISA assays were used to assess for TNF‐α and IL-6 in vitro and in vivo. Nuclear and cytoplasmic protein extraction and Confocal microscopy were applied to verify the translocation of NF‐κB. Mechanically, co-immunoprecipitation and rescue experiments were used to validate the regulation of USP10 and NEMO. Results: In macrophages, we found that LPS induced USP10 upregulation. The inhibition or knockdown of USP10 reduced the pro‐inflammatory cytokines TNF-α and IL-6 and suppressed LPS‐induced NF‐κB activation by regulating the translocation of NF‐κB. Furthermore, we found that NEMO, the regulatory subunit NF-κB essential modulator, was essential for the regulation of LPS-induced inflammation by USP10 in macrophages. NEMO protein evidently interacted with USP10, whereby USP10 inhibition accelerated the degradation of NEMO. Suppressing USP10 significantly attenuated inflammatory responses and improved the survival rate in LPS-induced sepsis mice. Conclusions: Overall, USP10 was shown to regulate inflammatory responses by stabilizing the NEMO protein, which may be a potential therapeutic target for sepsis-induced lung injury. [ABSTRACT FROM AUTHOR]

Background: In-stent restenosis (ISR) remains a challenge for coronary artery disease (CAD) patients who undergo percutaneous coronary intervention (PCI) with stents, and risk factors for ISR are controversial. This study aimed to investigate the incidence and risk factors of ISR in patients from southern China. Methods: In this retrospective study, patients diagnosed as acute coronary syndromes (ACS) and underwent successful PCI with drug-eluting stent (DES) and conducted a follow-up coronary angiography in Center for Cardiovascular Diseases of Meizhou People's Hospital at the period of January 1st, 2016 to January 1st, 2021 were included for analysis. The clinical and angiographic factors were compared between patients in ISR (+) and ISR (−) groups. The association between variables and ISR was evaluated by multivariate logistic regression model. Result: A total of 341 ACS patients who had been installed at least 1 stent were included in this study. The follow-up time was 34.2 ± 17.2 months. During the follow-up period, 62 (18.2%) patients experienced ISR, and the average time for ISR was 32.8 months; the incidence of ISR for left main coronary artery, left anterior descending coronary artery, left circumflex artery coronary artery and right coronary artery were 6.7%, 20.9%, 19.4% and 14.4%, respectively; left ventricular ejection fraction (LVEF), stent number, stent type, statin therapy, antiplatelet therapy were significantly different between patients in ISR (+) and ISR (−) group. Multivariate logistic analysis suggested that LVEF and stent number were significantly correlated with ISR. Conclusion: Our study revealed the incidence and risk factors of ISR in patients from southern China. Our data suggested that LVEF and stent number were independent risk factors associated with ISR. [ABSTRACT FROM AUTHOR]

Background: Acute coronary syndrome (ACS) is a complex cardiovascular disease whose development involves the dysregulation of adaptive immune responses. Though it has been proven that T cells associate with inflammation in the development of ACS, the function of B cells in disease remains unclear. Objective: The aim of this study was to reveal the diversity of the B cell receptor (BCR) repertoire of patients with ACS. Methods: We conducted a pilot study to sequence the immune repertoire of peripheral blood mononuclear cells (PBMCs) from patients with ACS, including acute myocardial infarction (AMI) and unstable angina (UA), and quantitatively characterized BCR repertoires by bioinformatics analysis. Results: We found that patients with AMI and UA had lower BCR repertoire diversity compared with controls with normal coronary arteries (NCA). Lower percentages of productive unique BCR nt sequences and higher percentages of top 200 unique BCR sequences were identified in AMI and UA patients than NCA controls. Patients had various preferential usage of V and J genes from B cell clones in accordance with the disease severity of coronary arteries. AMI patients had distinct CDR3 amino acids, and their frequency differed among patients with ACS. Conclusions: Our results indicate that differential BCR signatures represent an imprint of distinct repertoires among ACS patients. This study thereby opens up the prospect of studying disease-relevant B cells to better understand and treat ACS. [ABSTRACT FROM AUTHOR]

Objectives: This retrospective study aimed to analyze the clinical and laboratory features, disease activity, and outcomes of juvenile systemic lupus erythematosus (jSLE) patients from southern China. Methods: A total of 173 jSLE patients who attended Rheumatology and Immunology Department of Meizhou People's Hospital between January 2010 and December 2019 are included for analysis. Results: The mean age of disease onset was 13.65 ± 2.80 (range, 5–17). The median age at diagnosis was 13.98 ± 2.88 (range, 5–17) years. The female to male ratio was 6.5:1. Renal involvement was the most prevalent clinical feature, occurred in 71.7% of the patients. A total of 27 (15.6%) patients underwent renal biopsy, and the most common type of renal pathology was class IV (44.4%). Our study demonstrated differences in antibody clusters for which the positivity rates of anti-dsDNA antibodies and anti-Sm antibodies were higher than the other jSLE cohorts reported in China and worldwide. Cyclophosphamide combined with corticosteroids was the main treatment medication. The mean SLE Disease Activity Index (SLEDAI) score at diagnosis was 14.3 ± 7.6 (range, 3–38). Five patients died during the initial diagnosis and treatment. Infection was the major cause of death. Conclusion: The jSLE patients in this cohort had a higher prevalence of renal involvement, anti-dsDNA antibodies, and anti-Sm antibodies. Multicenter studies are needed to clarify the different clinical features of jSLE in southern China. Key Points: • A single-center study of juvenile systemic lupus erythematosus in clinical and laboratory features. • The jSLE patients had a higher prevalence of renal involvement and antibody disorder. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the T-cell receptor (TCR) repertoire in patients with acute coronary syndrome (ACS).Methods: The TCR repertoires of 9 unstable angina patients (UA), 14 acute myocardial infarction patients (AMI) and 9 normal coronary artery (NCA) patients were profiled using high-throughput sequencing (HTS). The clonal diversity of the TCR repertoires in different groups was analyzed, as well as the frequencies of variable (V), diversity (D) and joining(J) gene segments.Results: ACS patients including UA and AMI, showed reduced TCRβ diversity than NCA patients. ACS patients presented higher levels of clonal expansion. The clonotype overlap of complementarity determining region 3(CDR3) was significantly varied between different groups. A total of 10 V genes and 1 J gene were differently utilized between ACS and NCA patients. We identified some shared CDR3 amino acid sequences that were presented in ACS but not in NCA patients.Conclusions: This study revealed the distinct TCR repertoires in patients with ACS and demonstrated the presence of disease associated T-cell clonotypes. These findings suggested a role of T cells in ACS and provided a new way to explore the mechanisms of ACS. [ABSTRACT FROM AUTHOR]

Background: The role of apolipoprotein E gene (APOE) in lipid metabolism has been well established, and APOE is associated with the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). However, the relationship between APOE polymorphisms and type 2 diabetes (T2DM) with or without CVD remains unclear.Methods: In this cross-sectional study, a total of 924 participants including 211 controls (CVD-T2DM-), 247 T2DM patients with CVD (CVD-T2DM+), 232 CVD patients without T2DM (CVD + T2DM-) and 234 T2DM patients with CVD (CVD + T2DM+), were genotyped using chip platform. The association between APOE polymorphisms and T2DM patients with or without CVD was analyzed by univariable and multivariable logistic analysis.Results: The present study showed that the frequency of E3/E4 increased in T2DM patients with CVD (p < 0.01). The ε4 allele was higher in CVD patients without T2DM (p < 0.01) and T2DM patients with CVD (p < 0.01) as compared with the controls.Conclusions: The subjects carrying ε4 allele have increased risk of CVD and T2DM, and exhibit higher level of lipid profiles. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis(M.tb), which causes tuberculosis, is a host-adapted intracellular pathogen that can live within macrophages owning to its ability to arrest phagolysosome biogenesis. The guanine nucleotide exchange factor H1 (GEF-H1) may contribute to the phagocytosis of bacteria by macrophages through mediating the crosstalk between microtubules and the actin cytoskeleton. Its role inShigellainfection has been determined but little is known about the role of GEF-H1 in mycobacterial infection. In the present study, we demonstrated that GEF-H1 functioned as a key regulator of the macrophage-mediated anti-mycobacterial response. We found that both mRNA and protein expression levels of GEF-H1 were significantly upregulated in macrophage during mycobacterial infection. Moreover, silencing of GEF-H1 with specific siRNAs reduced the phosphorylation of p38 mitogen-activated protein kinase and TANK binding kinase 1 as well as the expression of interleukin-1β (IL-1β), IL-6, and interferon-β (IFN-β), without affecting nitric oxide production or autophagy. Importantly, GEF-H1 depletion attenuated macrophages-mediated mycobacterial phagocytosis and elimination. Taken together, our data supported that GEF-H1 was a novel regulator of inflammatory cytokine production and mycobacterial elimination, and may serve as a novel potential target for clinical treatment of tuberculosis. [ABSTRACT FROM PUBLISHER]

The aim of this study was to establish plasma cytokine/chemokine profiles in patients with 3 different presentations of active tuberculosis (TB), compared to the profiles observed in bacillus Calmette-Guérin (BCG)-vaccinated healthy individuals and patients with other pulmonary diseases (non-TB patients). To this end, plasma samples were collected from 151 TB patients including 68 pulmonary TB (PTB), 43 endobronchial TB, and 40 tuberculosis pleurisy (TP) patients, as well as 107 no-TB cases including 26 non-TB patients and 81 BCG-vaccinated healthy controls. A liquid array-based multiplexed immunoassay was used to screen plasma samples for 20 distinct cytokines and chemokines. Multinomial logistic regression was used to analyze associations between cytokines/chemokines and TB/non-TB patients. Compared to our findings with the no-TB donors, the median plasma levels of the proinflammatory cytokines/chemokines TNF-α, IL-6, IP-10, IFN-γ, and MIP-1β were significantly elevated in TB patients, suggesting their potential use as biomarkers for diagnosing TB patients. Further comparisons with healthy donors showed that only the median TNF-α plasma level was highly produced in the plasma of all 3 types of TB patients. Plasma IL-6 production was higher only in TP patients, while the plasma levels of IP-10, IFN-γ, and MIP-1β were markedly enhanced in both PTB and TP patients. Unexpectedly, among the above cytokines/chemokines, MIP-1β was also highly expressed in non-TB patients, compared with healthy donors. Our results suggested that TNF-α may be an ideal biomarker for diagnosing the 3 forms of TB presentation, while the other factors (IL-6, IP-10, MCP-1, and IFN-γ) can potentially facilitate differential diagnosis for the 3 TB presentation types. Further characterization of immune responses associated with different types of TB diseases will provide a basis for developing novel TB diagnostics. [ABSTRACT FROM AUTHOR]

Background: Potent antitumor responses can be induced through cytokine immunotherapy. Interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) are among the most effective cytokines to induce tumor-specific systemic immune responses and can act synergistically. To overcome the limitations of combined use of these two cytokines, we have constructed an IL2-GMCSF fusion protein and characterized its antitumor effects in this study.Methods: The expression of IL-2 receptor and GM-CSF receptor of cell lines were detected with quantitative real-time PCR. On this basis, the bioactivities of IL2-GMCSF, especially effects on DC2.4 cells were assayed. Another function of IL2-GMCSF-bridge two types of cells-was assessed by cell contact counting and cytotoxicity assays. The anti-tumor activity in vivo of IL2-GMCSF was evaluated in the melanoma model. The statistical significance among treatment groups were determined by One-Way ANOVA.Results: The fusion protein IL2-GMCSF maintained the activities of IL-2 and GM-CSF, and could significantly promote DC2.4 cell activities, including phagocytosis, proliferation and cytokine secretion. In addition to the inherent cytokine activity, IL2-GMCSF bridges direct cell-cell interactions and enhances splenocyte killing efficacy against multiple tumor cell lines in vitro. Co-injection of IL2-GMCSF and inactivated B16F10 mouse melanoma cells induced complete immunoprotective responses in about 30 % of mice.Conclusion: These results suggested that IL2-GMCSF can efficiently regulate immune responses against tumors. Furthermore, as the bridging effect relies on both IL-2R and GM-CSFR and promotes interactions between immune and tumor cells, IL2-GMCSF may be utilized as a useful tool for dissecting specific immune responses for future clinical applications. [ABSTRACT FROM AUTHOR]

Background: Recurrence of colorectal polyps is common and impacted by various factors. This study was performed to explore the association between lipid profiles and recurrence of colorectal polyps. Methods: This study retrospectively analyzed the lipid profiles of 435 patients who underwent colonoscopy with removal of colorectal polyps and assessed recurrence of polyps by follow-up colonoscopy. Multivariate regression logistic analysis was used to evaluate the association between lipid profiles and polyp recurrence. Results: During the 1.5-year follow-up, recurrence of colorectal polyps was observed in 135 of 435 patients (30.34%). Patients with recurrent polyps showed a higher level of triglycerides (P = 0.006) and lower levels of high-density lipoprotein cholesterol (P = 0.008) and apolipoprotein A1 (P = 0.033). The multivariate regression logistic model suggested that an elevated triglyceride level was an independent risk factor for polyp recurrence (odds ratio, 1.55; 95% confidence interval, 1.02–2.35; P = 0.039) in patients with advanced adenoma. Conclusions: Lipid profiles are associated with recurrence of colorectal polyps. An elevated triglyceride level is an independent risk predictor of polyp recurrence in patients with advanced adenoma. [ABSTRACT FROM AUTHOR]

Rabies, caused by rabies virus (RABV), is still the deadliest infectious disease. Mechanism of host immune response upon RABV infection is not yet fully understood. Accumulating evidences suggest that long noncoding RNAs (lncRNAs) plays key roles in host antiviral responses. However, expression profile and function of lncRNAs in RABV infection remain unclear. In the present study, expression profile of lncRNAs and mRNAs profiles were investigated in RABV-infected brain tissues of mice by RNA sequencing. A total of 140 lncRNAs and 3,807 mRNAs were differentially expressed in RABV-infected animals. The functional annotation and enrichment analysis using Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that differentially expressed transcripts were predominantly involved in signaling pathways related to host immune response. The expression profiles of the selected lncRNAs in brains of mice during RABV infections were verified by quantitative real time polymerase chain reaction (qRT-PCR). To our knowledge, this is the first report to profile the lncRNA expression in RABV infected mice. Our findings provide insights into understanding the role of lncRNAs in host immune response against RABV infection. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) DNA testing is an important method in cervical cancer screening. However, the studies on prevalence and genotype distribution of HPV among women in northeastern Guangdong Province of China are very limited.Methods: A total of 28,730 women attending the Department of Gynecology of Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University between January 1st, 2013 and June 1st, 2015 were enrolled in this study. HPV type-specific distribution was tested using flow-through hybridization and gene chip.Results: The overall prevalence of HPV infection was 19.81%, among which 79.09% were infected with high-risk HPV subtypes in the subjects. The 5 most predominant genotypes were HPV16, 52, 58, 18 and 81. Most HPV infections were observed in women aged 41-50 and women aged 30-59 accounted for a proportion of over 80%.Conclusions: Our findings suggested a high burden of HPV infection among women in northeastern Guangdong Province of China. We identified the top 5 HPV genotypes as well as the age-specific distribution of HPV infections in this area. [ABSTRACT FROM AUTHOR]

Macrophages play a crucial role in the control and elimination of invading Mycobacterium tuberculosis (Mtb), and also serve as the major residence for Mtb. However, the interaction between macrophages and Mtb remains to be clearly determined. Although long noncoding RNAs (lncRNAs) have emerged as key regulators in many biological processes, their roles in anti-mycobacterial responses of macrophages remain to be elucidated. Here, we applied microarray analysis to examine lncRNA and mRNA expression profiles in human primary macrophages after 72 h of infection with H37Ra or H37Rv. Our results revealed that many lncRNAs were differentially expressed in macrophages after H37Ra or H37Rv infection, indicating a possible role for lncRNAs in immune responses induced by Mtb infection and providing important cues for further functional studies. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis of the differentially expressed mRNAs showed the potential functions and pathways related to the pathogenesis of Mtb infection. Finally, two lncRNAs, MIR3945HG V1 and MIR3945HG V2, were identified as novel candidate diagnostic markers for tuberculosis. Our results provide novel insight into the mechanisms of the pivotal Mtb-macrophage interactions, and reveal potential targets for diagnostics and the treatment of tuberculosis. [ABSTRACT FROM AUTHOR]