Role and therapeutic potential of gelsolin in atherosclerosis.

Atherosclerosis is the major pathophysiological basis of a variety of cardiovascular diseases and has been recognized as a lipid-driven chronic inflammatory disease. Gelsolin (GSN) is a member of the GSN family. The main function of GSN is to cut and seal actin filaments to regulate the cytoskeleton and participate in a variety of biological functions, such as cell movement, morphological changes, metabolism, apoptosis and phagocytosis. Recently, more and more evidences have demonstrated that GSN is Closely related to atherosclerosis, involving lipid metabolism, inflammation, cell proliferation, migration and thrombosis. This article reviews the role of GSN in atherosclerosis from inflammation, apoptosis, angiogenesis and thrombosis.

Asprosin inhibits macrophage lipid accumulation and reduces atherosclerotic burden by up-regulating ABCA1 and ABCG1 expression via the p38/Elk-1 pathway.

BACKGROUND: Asprosin, a newly discovered adipokine, is a C-terminal cleavage product of profibrillin. Asprosin has been reported to participate in lipid metabolism and cardiovascular disease, but its role in atherogenesis remains elusive. METHODS: Asprosin was overexpressed in THP-1 macrophage-derived foam cells and apoE-/- mice using the lentiviral vector. The expression of relevant molecules was determined by qRT-PCR and/or western blot. The intracellular lipid accumulation was evaluated by high-performance liquid chromatography and Oil red O staining. HE and Oil red O staining was employed to assess plaque burden in vivo. Reverse cholesterol transport (RCT) efficiency was measured using [3H]-labeled cholesterol. RESULTS: Exposure of THP-1 macrophages to oxidized low-density lipoprotein down-regulated asprosin expression. Lentivirus-mediated overexpression of asprosin promoted cholesterol efflux and inhibited lipid accumulation in THP-1 macrophage-derived foam cells. Mechanistic analysis revealed that asprosin overexpression activated p38 and stimulated the phosphorylation of ETS-like transcription factor (Elk-1) at Ser383, leading to Elk-1 nuclear translocation and the transcriptional activation of ATP binding cassette transporters A1 (ABCA1) and ABCG1. Injection of lentiviral vector expressing asprosin diminished atherosclerotic lesion area, increased plaque stability, improved plasma lipid profiles and facilitated RCT in apoE-/- mice. Asprosin overexpression also increased the phosphorylation of p38 and Elk-1 as well as up-regulated the expression of ABCA1 and ABCG1 in the aortas. CONCLUSION: Asprosin inhibits lipid accumulation in macrophages and decreases atherosclerotic burden in apoE-/- mice by up-regulating ABCA1 and ABCG1 expression via activation of the p38/Elk-1 signaling pathway.

Astragalin Retards Atherosclerosis by Promoting Cholesterol Efflux and Inhibiting the Inflammatory Response via Upregulating ABCA1 and ABCG1 Expression in Macrophages.

ABSTRACT: Lipid metabolism disorder and inflammatory response are considered to be the major causes of atherosclerogenesis. Astragalin, the most important functional component of flavonoid obtained from persimmon leaves, has the hypolipidemic effects. However, it is unknown, how astragalin protects against atherosclerosis. The aim of this study was to observe the effects of astragalin on cholesterol efflux and inflammatory response and to explore the underlying mechanisms. Our results showed that astragalin upregulated the expression of ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1), promoted cholesterol efflux, and suppressed foam cell formation. Inhibition of the PPARγ/LXRα pathway abrogated the promotive effects of astragalin on both transporter expression and cholesterol efflux. In addition, treatment of astragalin markedly decreased the secretion of inflammatory factors, including interleukin 6, monocyte chemotactic protein 1, tumor necrosis factor α, and interleukin 1ß. Mechanistically, astragalin upregulated ABCA1 and ABCG1 expression, which in turn reduced TLR4 surface levels and inhibited NF-κB nuclear translocation. Consistently, astragalin reduced atherosclerotic plaque area in apoE-/- mice. Taken together, these findings suggest that astragalin protects against atherosclerosis by promoting ABCA1- and ABCG1-mediated cholesterol efflux and inhibiting proinflammatory mediator release.

Myristica fragrans promotes ABCA1 expression and cholesterol efflux in THP-1-derived macrophages.

Myristica fragrans is a traditional herbal medicine and has been shown to alleviate the development of atherosclerosis. However, the anti-atherogenic mechanisms of M. fragrans are still to be addressed. In this study, we explored the effect of M. fragrans on lipid metabolism and inflammation and its mechanisms in THP-1-derived macrophages. The quantitative polymerase chain reaction and western blot analysis results showed that M. fragrans promotes cholesterol efflux from THP-1-derived macrophages and reduces intracellular total cholesterol, cholesterol ester, and free cholesterol contents in a dose- and a time-dependent manner. Further study found that liver X receptor alpha (LXRα) antagonist GGPP significantly blocked the upregulation of ABCA1 expression with M. fragrans treatment. In addition, chromatin immunoprecipitation assay confirmed that GATA binding protein 3 (GATA3) can bind to the LXRα promoter, and inhibition of GATA3 led to the downregulation of LXRα and ATP-binding cassette subfamily A member 1 expression. Furthermore, M. fragrans reduced lipid accumulation, followed by decreasing tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß and increasing IL-10 produced by THP-1-derived macrophages. Therefore, M. fragrans is identified as a valuable therapeutic medicine for atherosclerotic cardiovascular disease.

The Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript-1 Regulates CCDC80 Expression by Targeting miR-141-3p/miR-200a-3p in Vascular Smooth Muscle Cells.

OBJECTIVE: Our previous study showed that Coiled-Coil Domain Containing 80 (CCDC80) accelerates the development of atherosclerosis by decreasing lipoprotein lipase (LPL) expression and activity in apoE knockout mice. However, the regulatory mechanism for CCDC80 expression is unclear. This study was designed to evaluate whether noncoding RNAs involved the regulation of CCDC80 expression in vascular smooth muscle cells. METHODS AND RESULTS: Bioinformatics prediction and luciferase reporter gene results showed that miR-141-3p/200a-3p bound to the 3'UTR of CCDC80. Furthermore, miR-141-3p/200a-3p mimics decreased the expression of CCDC80 but increased LPL expression. Opposite results were observed with miR-141-3p/200a-3p inhibitors. We also found that lncRNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) interacted with the sequences of miR-141-3p/200a-3p and decreased their expression. RT-qPCR and western blotting results showed that MALAT1 overexpression increased CCDC80 expression and decreased LPL expression, while MALAT1 knockdown displayed an opposite phenotype. The effects of both MALAT1 overexpression and knockdown were blocked by miR-141-3p/200a-3p mimics or inhibitors. CONCLUSIONS: Thus, we demonstrated that lncRNA MALAT1 regulates CCDC80 and LPL expression through miR-141-3p/200a-3p.

Interleukin-5 promotes ATP-binding cassette transporter A1 expression through miR-211/JAK2/STAT3 pathways in THP-1-dervied macrophages.

Interleukin-5 (IL-5) is manifested as its involvement in the process of atherosclerosis, but the mechanism is still unknown. In this study, we explored the effect of IL-5 on lipid metabolism and its underlying mechanisms in THP-1-derived macrophages. The quantitative polymerase chain reaction (qPCR) and western blot analysis results showed that IL-5 significantly up-regulated ATP-binding cassette transporter A1 (ABCA1) expression in a dose-dependent and time-dependent manner. [3H]-labeled cholesterol was used to assess the levels of cholesterol efflux, and the results showed that IL-5 increased ABCA1-mediated cholesterol efflux. A high-performance liquid chromatography assay indicated that cellular cholesterol content was decreased by IL-5 treatment in THP-1-derived macrophages. The selective inhibitor and small interfering RNA were used to block the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway. The results of the qPCR and western blot analysis showed that IL-5 activated JAK2/STAT3 pathway to up-regulate ABCA1 expression. Meanwhile, IL-5 reduced the expression level of miR-211. Furthermore, we found that JAK2 is a target gene of miR-211 and miR-211 mimic inhibited the expression of JAK2 and reduced the levels of p-STAT3 and ABCA1 as revealed by luciferase reporter assay, qPCR and western blot analysis. In summary, these findings indicated that IL-5 promotes ABCA1 expression and cholesterol efflux through the miR-211/JAK2/STAT3 signaling pathway in THP-1-derived macrophages.

CXCL12 promotes atherosclerosis by downregulating ABCA1 expression via the CXCR4/GSK3ß/ß-cateninT120/TCF21 pathway.

CXC chemokine ligand 12 (CXCL12) is a member of the CXC chemokine family and mainly acts on cell chemotaxis. CXCL12 also elicits a proatherogenic role, but the molecular mechanisms have not been fully defined yet. We aimed to reveal if and how CXCL12 promoted atherosclerosis via regulating lipid metabolism. In vitro, our data showed that CXCL12 could reduce ABCA1 expression, and it mediated cholesterol efflux from THP-1-derived macrophages to apoA-I. Data from the luciferase reporter gene and chromatin immunoprecipitation assays revealed that transcription factor 21 (TCF21) stimulated the transcription of ABCA1 via binding to its promoter region, which was repressed by CXCL12. We found that CXCL12 increased the levels of phosphorylated glycogen synthase kinase 3ß (GSK3ß) and the phosphorylation of ß-catenin at the Thr120 position. Inactivation of GSK3ß or ß-catenin increased the expression of TCF21 and ABCA1. Further, knockdown or inhibition of CXC chemokine receptor 4 (CXCR4) blocked the effects of CXCL12 on TCF21 and ABCA1 expression and the phosphorylation of GSK3ß and ß-catenin. In vivo, the overexpression of CXCL12 in Apoe-/- mice via lentivirus enlarged the atherosclerotic lesion area and increased macrophage infiltration in atherosclerotic plaques. We further found that the overexpression of CXCL12 reduced the efficiency of reverse cholesterol transport and plasma HDL-C levels, decreased ABCA1 expression in the aorta and mouse peritoneal macrophages (MPMs), and suppressed cholesterol efflux from MPMs to apoA-I in Apoe-/- mice. Collectively, these findings suggest that CXCL12 interacts with CXCR4 and then activates the GSK-3ß/ß-cateninT120/TCF21 signaling pathway to inhibit ABCA1-dependent cholesterol efflux from macrophages and aggravate atherosclerosis. Targeting CXCL12 may be a novel and promising strategy for the prevention and treatment of atherosclerotic cardiovascular diseases.

IL-8 negatively regulates ABCA1 expression and cholesterol efflux via upregulating miR-183 in THP-1 macrophage-derived foam cells.

OBJECTIVE: Previous studies suggest that IL-8 has an important role in the regulation of cholesterol efflux, but whether miRNAs are involved in this process is still unknown. The purpose of this study is to explore whether IL-8 promotes cholesterol accumulation by enhancing miR-183 expression in macrophages and its underlying mechanism. METHODS AND RESULTS: Treatment of THP-1 macrophage-derived foam cells with IL-8 decreased ABCA1 expression and cholesterol efflux. Using bioinformatics analyses and dual-luciferase reporter assays, we found that miR-183 was highly conserved during evolution and directly inhibited ABCA1 protein and mRNA expression by targeting ABCA1 3'UTR. MiR-183 directly regulated endogenous ABCA1 expression levels. Furthermore, IL-8 enhanced the expression of miR-183 and decrease ABCA1 expression. Cholesterol transport assays confirmed that IL-8 dramatically inhibited apolipoprotein AI-mediated ABCA1-dependent cholesterol efflux by increasing miR-183 expression. In contrast, treatment with anti-IL-8 antibody reversed these effects. CONCLUSION: IL-8 enhances the expression of miR-183, which then inhibits ABCA1 expression and cholesterol efflux. Our studies suggest that the IL-8-miR-183-ABCA1 axis may play an intermediary role in the development of atherosclerosis.

Pregnancy-Associated Plasma Protein-A Accelerates Atherosclerosis by Regulating Reverse Cholesterol Transport and Inflammation.

BACKGROUND: Recent studies have suggested that pregnancy-associated plasma protein-A (PAPP-A) is involved in the pathogenesis of atherosclerosis. This study aim is to investigate the role and mechanisms of PAPP-A in reverse cholesterol transport (RCT) and inflammation during the development of atherosclerosis. Methods and Results: PAPP-A was silenced in apolipoprotein E (apoE-/-) mice with administration of PAPP-A shRNA. Oil Red O staining of the whole aorta root revealed that PAPP-A knockdown reduced lipid accumulation in aortas. Oil Red O, hematoxylin and eosin (HE) and Masson staining of aortic sinus further showed that PAPP-A knockdown alleviated the formation of atherosclerotic lesions. It was found that PAPP-A knockdown reduced the insulin-like growth factor 1 (IGF-1) levels and repressed the PI3K/Akt pathway in both aorta and peritoneal macrophages. The expression levels of LXRα, ABCA1, ABCG1, and SR-B1 were increased in the aorta and peritoneal macrophages from apoE-/-mice administered with PAPP-A shRNA. Furthermore, PAPP-A knockdown promoted RCT from macrophages to plasma, the liver, and feces in apoE-/-mice. In addition, PAPP-A knockdown elevated the expression and secretion of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), tumor necrosis factor-α, and interleukin-1ß through the nuclear factor kappa-B (NF-κB) pathway. CONCLUSIONS: The present study results suggest that PAPP-A promotes the development of atherosclerosis in apoE-/-mice through reducing RCT capacity and activating an inflammatory response.

Heat shock protein 70 accelerates atherosclerosis by downregulating the expression of ABCA1 and ABCG1 through the JNK/Elk-1 pathway.

BACKGROUND AND AIMS: Recent studies have suggested that heat shock protein 70 (HSP70) may play critical roles in cardiovascular disease. However, the effects of HSP70 on the development of atherosclerosis in apoE-/- mice remain largely unknown. This study was to investigate the role and potential mechanism of HSP70 in atherosclerosis. METHODS: HSP70 was overexpressed in apoE-/- mice and THP-1-derived macrophages with lentiviral vectors. Oil Red O, hematoxylin-eosin, and Masson staining were performed to evaluate atherosclerotic plaque in apoE-/- mice fed the Western type diet. Moreover, immunostaining was employed to detect the expression of relative proteins in aortic sinus. Reporter gene and chromatin immunoprecipitation were performed to analyze the effect of Elk-1 on the promoter activity of ABCA1 and ABCG1; [3H] labeled cholesterol was used to assess the capacity of cholesterol efflux and reverse cholesterol transport (RCT). RESULTS: Our results showed that HSP70 increased lipid accumulation in arteries and promoted the formation of atherosclerotic lesion. The capacity of cholesterol efflux was reduced in peritoneal macrophages isolated from HSP70-overexpressed apoE-/- mice. The levels of ABCA1 and ABCG1 expression were also reduced in the peritoneal macrophages and the aorta from apoE-/- mice in response to HSP70. The c-Jun N-terminal kinase (JNK) and ETS transcription factor (Elk-1) played a critical role in HSP70-induced downregulation ABCA1 and ABCG1. Further, HSP70 reduced RCT from macrophages to plasma, liver, and feces in apoE-/- mice. CONCLUSIONS: HSP70 promotes the progression of atherosclerosis in apoE-/- mice by suppressing the expression of ABCA1 and ABCG1 through the JNK/Elk-1 pathway.

Apolipoprotein A-1 Binding Protein Inhibits Inflammatory Signaling Pathways by Binding to Apolipoprotein A-1 in THP-1 Macrophages.

BACKGROUND: It has previously been demonstrated that apolipoprotein A-1 (apoA-1) binding protein (AIBP) promotes apoA-1 binding to ATP-binding cassette transporter A1 (ABCA1) and prevents ABCA1 protein degradation so as to inhibit foam cell formation. Because apoA-1 inhibits inflammatory signaling pathways, whether AIBP has an inhibitory effect on inflammatory signaling pathways in THP-1-derived macrophages is investigated.Methods and Results:Analysis of inflammation-related gene expression indicated that AIBP decreased lipopolysaccharide (LPS)-mediated macrophage inflammation. AIBP significantly prevented NF-κB nuclear translocation. Further, AIBP prevented the activation of mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular-signal regulated kinase and c-Jun N-terminal kinase. AIBP decreased MyD88 expression at both mRNA and protein levels, but did not have any effect on TLR4 expression. Moreover, treatment with both AIBP and apoA-1 decreased the abundance of TLR4 in the lipid raft fraction. AIBP lacking 115-123 amino acids (∆115-123), however, did not have such effects as described for intact AIBP. In addition, knockdown of ABCA1 inhibited the effects of AIBP on inflammatory factor secretion. CONCLUSIONS: These results suggest that AIBP inhibits inflammatory signaling pathways through binding to apoA-1 and stabilizing ABCA1, and subsequent alteration of lipid rafts and TLR4 in the cell membrane.

MicroRNA-377 Inhibits Atherosclerosis by Regulating Triglyceride Metabolism Through the DNA Methyltransferase 1 in Apolipoprotein E-Knockout Mice.

BACKGROUND: Lipoprotein lipase (LPL) plays an important role in triglyceride metabolism. It is translocated across endothelial cells to reach the luminal surface of capillaries by glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1), where it hydrolyzes triglycerides in lipoproteins. MicroRNA 377 (miR-377) is highly associated with lipid levels. However, how miR-377 regulates triglyceride metabolism and whether it is involved in the development of atherosclerosis remain largely unexplored. Methods and Results: The clinical examination displayed that miR-377 expression was markedly lower in plasma from patients with hypertriglyceridemia compared with non-hypertriglyceridemic subjects. Bioinformatics analyses and a luciferase reporter assay showed that DNA methyltransferase 1 (DNMT1) was a target gene of miR-377. Moreover, miR-377 increased LPL binding to GPIHBP1 by directly targeting DNMT1 in human umbilical vein endothelial cells (HUVECs) and apolipoprotein E (ApoE)-knockout (KO) mice aorta endothelial cells (MAECs). In vivo, hematoxylin-eosin (H&E), Oil Red O and Masson's trichrome staining showed that ApoE-KO mice treated with miR-377 developed less atherosclerotic plaques, accompanied by reduced plasma triglyceride levels. CONCLUSIONS: It is concluded that miR-377 upregulates GPIHBP1 expression, increases the LPL binding to GPIHBP1, and reduces plasma triglyceride levels, likely through targeting DNMT1, inhibiting atherosclerosis in ApoE-KO mice.

MicroRNA-182 Promotes Lipoprotein Lipase Expression and Atherogenesisby Targeting Histone Deacetylase 9 in Apolipoprotein E-Knockout Mice.

BACKGROUND: Lipoprotein lipase (LPL) expressed in macrophages plays an important role in promoting the development of atherosclerosis or atherogenesis. MicroRNA-182 (miR-182) is involved in the regulation of lipid metabolism and inflammation. However, it remains unclear how miR-182 regulates LPL and atherogenesis.Methods and Results:Using bioinformatics analyses and a dual-luciferase reporter assay, we identified histone deacetylase 9 (HDAC9) as a target gene of miR-182. Moreover, miR-182 upregulated LPL expression by directly targetingHDAC9in THP-1 macrophages. Hematoxylin-eosin (H&E), Oil Red O and Masson's trichrome staining showed that apolipoprotein E (ApoE)-knockout (KO) mice treated with miR-182 exhibited more severe atherosclerotic plaques. Treatment with miR-182 increased CD68 and LPL expression in atherosclerotic lesions in ApoE-KO mice, as indicated by double immunofluorescence staining in the aortic sinus. Increased miR-182-induced increases in LPL expression in ApoE-KO mice was confirmed by real-time quantitative polymerase chain reaction and western blotting analyses. Treatment with miR-182 also increased plasma concentrations of proinflammatory cytokines and lipids in ApoE-KO mice. CONCLUSIONS: The results of the present study suggest that miR-182 upregulates LPL expression, promotes lipid accumulation in atherosclerotic lesions, and increases proinflammatory cytokine secretion, likely through targetingHDAC9, leading to an acceleration of atherogenesis in ApoE-KO mice.

Apelin-13 inhibits lipoprotein lipase expression via the APJ/PKCα/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells.

Atherosclerotic lesions are characterized by the accumulation of abundant lipids and chronic inflammation. Previous researches have indicated that macrophage-derived lipoprotein lipase (LPL) promotes atherosclerosis progression by accelerating lipid accumulation and pro-inflammatory cytokine secretion. Although apelin-13 has been regarded as an atheroprotective factor, it remains unclear whether it can regulate the expression of LPL. The aim of this study was to explore the effects of apelin-13 on the expression of LPL and the underlying mechanism in THP-1 macrophage-derived foam cells. Apelin-13 significantly decreased cellular levels of total cholesterol, free cholesterol, and cholesterol ester at the concentrations of 10 and 100 nM. ELISA analysis confirmed that treatment with apelin-13 reduced pro-inflammatory cytokine secretion, such as interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-alpha (TNF-α). It was also found that apelin-13 inhibited the expression of LPL as revealed by western blot and real-time PCR analyses. Bioinformatics analyses and dual-luciferase reporter assay indicated that miR-361-5p directly downregulated the expression of LPL by targeting the 3'UTR of LPL. In addition, apelin-13 + miR-361-5p mimic significantly downregulated the expression of LPL in cells. Finally, we demonstrated that apelin-13 downregulated the expression of LPL through activating the activity of PKCα. Taken together, our results showed that apelin-13 downregulated the expression of LPL via activating the APJ/PKCα/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells, leading to inhibition of lipid accumulation and pro-inflammatory cytokine secretion. Therefore, our studies provide important new insight into the inhibition of lipid accumulation and pro-inflammatory cytokine secretion by apelin-13, and highlight apelin-13 as a promising therapeutic target in atherosclerosis.

Cystathionine γ-lyase(CSE)/hydrogen sulfide system is regulated by miR-216a and influences cholesterol efflux in macrophages via the PI3K/AKT/ABCA1 pathway.

This study was designed to evaluate whether CSE/H2S system, which is regulated by miR-216a, regulated ABCA1-mediated cholesterol efflux and cholesterol contents in THP-1 macrophages-derived foam cells. Our qPCR and western blotting results showed that CSE/H2S significantly up-regulated the expression of ATP-binding cassette transporter A1 (ABCA1) mRNA and protein via PI3K/AKT pathway in foam cells derived from human THP-1 macrophages. The miR-216a directly targeted 3' untranslated region of CSE. It significantly reduced CSE and ABCA1 expression, and also decreased the phosphorylation of PI3K and AKT. Additionally, cholesterol efflux decreased, and cholesterol levels increased in THP-1 macrophage-derived foam cells in response to treatment with miR-216a. Our study demonstrates that CSE/H2S system is regulated by miR-216a, and regulates ABCA1-mediated cholesterol efflux and cholesterol levels through the PI3K/AKT pathway.

TM9SF1 offers utility as an efficient predictor of clinical severity and mortality among acute respiratory distress syndrome patients.

Introduction: Acute respiratory distress syndrome (ARDS) is a major cause of death among critically ill patients in intensive care settings, underscoring the need to identify biomarkers capable of predicting ARDS patient clinical status and prognosis at an early time point. This study specifically sought to explore the utility and clinical relevance of TM9SF1 as a biomarker for the early prediction of disease severity and prognostic outcomes in patients with ARDS. Methods: This study enrolled 123 patients with severe ARDS and 116 patients with non-severe ARDS for whom follow-up information was available. The mRNA levels of TM9SF1 and cytokines in peripheral blood mononuclear cells from these patients were evaluated by qPCR. The predictive performance of TM9SF1 and other clinical indicators was evaluated using received operating characteristic (ROC) curves. A predictive nomogram was developed based on TM9SF1 expression and evaluated for its ability in the early prediction of severe disease and mortality in patients with ARDS. Results: TM9SF1 mRNA expression was found to be significantly increased in patients with severe ARDS relative to those with non-severe disease or healthy controls. ARDS severity increased in correspondence with the level of TM9SF1 expression (odds ratio [OR] = 2.43, 95% confidence interval [CI] = 2.15-3.72, P = 0.005), and high TM9SF1 levels were associated with a greater risk of mortality (hazard ratio [HR] = 2.27, 95% CI = 2.20-4.39, P = 0.001). ROC curves demonstrated that relative to other clinical indicators, TM9SF1 offered superior performance in the prediction of ARDS severity and mortality. A novel nomogram incorporating TM9SF1 expression together with age, D-dimer levels, and C-reactive protein (CRP) levels was developed and was used to predict ARDS severity (AUC = 0.887, 95% CI = 0.715-0.943). A separate model incorporating TM9SF1 expression, age, neutrophil-lymphocyte ratio (NLR), and D-dimer levels (C-index = 0.890, 95% CI = 0.627-0.957) was also developed for predicting mortality. Conclusion: Increases in ARDS severity and patient mortality were observed with rising levels of TM9SF1 expression. TM9SF1 may thus offer utility as a novel biomarker for the early prediction of ARDS patient disease status and clinical outcomes.

PDCD5 as a Potential Biomarker for Improved Prediction of the Incidence and Remission for Patients with Rheumatoid Arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) often involves an altered T-cell subpopulation, higher levels of inflammatory cytokines, and auto-antibodies. This study investigated whether PDCD5 could be a biomarker to predict the incidence and remission of RA so as to guide the therapeutic management of clinical RA. METHODS: One hundred fifty-two patients (41 being in both active status and stable remission status) who were newly diagnosed with RA and 38 healthy controls were enrolled. Basic clinical data were collected before using blood samples remaining in the clinic after routine complete blood count. The ability of PDCD5 and important indicators to predict the remission of RA was estimated based on receiver operating characteristic curve (ROC) analysis. RESULTS: PDCD5 expression was found to be significantly increased in RA patients in active status in comparison with healthy controls or those in stable remission status. Compared with anti-CCP, ESR and DAS28 score, PDCD5 was of better predictive value with an AUC of 0.846 (95% CI 0.780-0.912) for RA remission. The incidence risk of RA increased with higher levels of PDCD5 (OR = 1.73, 95% CI = 1.45-1.98, P = 0.005) in multiple logistic regression analysis, with the risk increasing by 2.94-times for high-risk group in comparison with low-risk group (OR = 2.94, 95% CI = 2.35-4.62, P < 0.001). The association between PDCD5 and RA remission showed a similar result. For correlation analysis, significant associations were eventually found between PDCD5 and indicated genes (FOXP3, TNF-α, IL-17A, IFN-γ and IL-6) as well as several important clinical parameters including IgG, RF, CRP, ESR, anti-CCP and DAS28 score. CONCLUSIONS: This study suggested that increased PDCD5 expression was significantly linked to the incidence and remission of RA. PDCD5 may be used as a novel biomarker for the prediction of RA incidence and remission, especially due to its potential involvement in the development of the condition.