Mediators of Inflammation最新文献

{"title":"The AMPK-mTOR Pathway Is Inhibited by Chaihu Shugan Powder, Which Relieves Nonalcoholic Steatohepatitis by Suppressing Autophagic Ferroptosis.","authors":"Zheng Liang, Dajin Pi, Jianwei Zhen, Haizhen Yan, Chuiyang Zheng, July Liang Chen, Wen Fan, Qingliang Song, Jinyue Pan, Dongdong Liu, Maoxing Pan, Qinhe Yang, Yupei Zhang","doi":"10.1155/2024/4777789","DOIUrl":"10.1155/2024/4777789","url":null,"abstract":"<p><p>Nonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), which is distinguished by the accumulation of fat in the liver, damage to liver cells, and inflammation. Chaihu Shugan powder (CSP), a renowned traditional Chinese medicine (TCM) blend extensively utilized in China to address liver disease, has demonstrated its efficacy in reducing lipid buildup and effectively combating inflammation. Hence, the primary objective of this research is to examine the impacts and possible mechanisms of CSP on NASH through assessments of liver histopathology, lipidomic analysis, and gene expression. To induce a mouse model of NASH, we employed a diet which deficient in methionine and choline, known as methionine-choline deficient (MCD) diet. Initially, we examined the impact of administering CSP to NASH mice by assessing the levels of serum and liver indicators. We found that CSP was able to reduce lipid buildup and inflammation in mice. In addition, a total of 1009 genes exhibited enrichment in both the autophagy and ferroptosis pathways. The liver protein levels of Adenosine monophosphate-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR)-mediated autophagy and ferroptosis markers, such as p-AMPK<i>α</i>/AMPK<i>α</i>, p-mTOR/mTOR, Beclin-1, microtubule associated protein 1 light chain 3 gamma (LC3), p62 (sequestosome 1 [SQSTM1/p62]), Kelch-like ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (Nrf-2), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPX4), were restored by CSP. Furthermore, our findings indicated that the suppression of autophagy had a repressive impact on the occurrence of ferroptosis in the mouse model, indicating that autophagy activation likely plays a role in mediating ferroptosis in NASH.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"4777789"},"PeriodicalIF":4.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Involvement of TANK-Binding Kinase 1 in the MyD88-Dependent NF-<i>κ</i>B Pathway Through Syk.","authors":"Han Gyung Kim, Ji Hye Kim, Tao Yu, Jae Youl Cho","doi":"10.1155/2024/8634515","DOIUrl":"10.1155/2024/8634515","url":null,"abstract":"<p><p>Inflammation is a vital immune defense mechanism regulated by Toll-like receptors (TLRs) and the nuclear factor-kappa B (NF-<i>κ</i>B) pathway. TANK-binding kinase 1 (TBK1) is central to immunity and inflammation and influences antiviral responses and cellular processes. However, the precise role of TBK1 in modulating the NF-<i>κ</i>B pathway through interactions with other proteins, such as spleen tyrosine kinase (Syk), remains poorly understood. As dysregulation of TBK1 and NF-<i>κ</i>B can lead to a variety of diseases, they are important therapeutic targets. In this work, inflammatory processes involving the TBK1-Syk-NF-<i>κ</i>B pathway were elucidated using lipopolysaccharide (LPS)-induced macrophages; human embryonic kidney 293 (HEK293) cells overexpressing MyD88, TBK1, and Syk proteins and their mutants; and real-time polymerase chain reaction (PCR), immunoblotting analyses, and kinase assays. TBK1 was activated in LPS-, poly I:C-, and Pam3CSK-stimulated macrophages. Transcript levels of <i>TNF</i>, <i>NOS2</i>, and <i>IL1B</i> were increased in cells overexpressing TBK1 but not in cells overexpressing TBK1 K38A. The transcription of <i>TNF</i>, <i>NOS2</i>, and <i>IL1B</i> and NF-<i>κ</i>B luciferase activity were inhibited by silencing TBK1 in LPS-stimulated RAW264.7 cells and MyD88-transfected HEK293 cells. Syk was the key mediator of the TBK1-dependent NF-<i>κ</i>B pathway and bound directly to the coiled coil domain of TBK1, which was necessary to activate Syk and the Syk-p85 pathway. This research advances the understanding of the role of TBK1 in NF-<i>κ</i>B signaling, emphasizing Syk as a key mediator. The interaction between TBK1 and Syk has potential for precise immune modulation that can be applied to treat immune-related disorders.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"8634515"},"PeriodicalIF":4.4,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy Improves Inflammatory Response in Sepsis Accompanied by Changes in Gut Microbiota.","authors":"La Wang, WenJia Wang, GuiTong Jiang, ZunLi Ke, RuiXi Luo, WeiYi Tian","doi":"10.1155/2024/9550301","DOIUrl":"10.1155/2024/9550301","url":null,"abstract":"<p><p><b>Background:</b> Sepsis is defined as a life-threatening disease. Autophagy and the microbiome are increasingly connected with sepsis. The aim of this study was to investigate the protective effect of autophagy and the possible mechanisms. <b>Methods:</b> The septic rat model was established by cecal ligation perforation (CLP). Rapamycin (Rap), 3-methyladenine (3-MA), and chloroquine (CQ) were administered to interfere autophagy. Western blot (WB) was used to detect the expression of key proteins in autophagy. Hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assays (ELISAs) were used to identify the effect of autophagy on various organs. 16S ribosomal RNA gene sequencing was used to analyze the changes of the gut microbiota. <b>Results:</b> Rap significantly upregulated the expression of key autophagy proteins, and 3-MA reduced the relative expression compared to the CLP group. The autophagic flux showed a corresponding trend. Interestingly, the autophagy inducer significantly decreased the mortality and the lipopolysaccharide (LPS) level in serum compared with the CLP group. Autophagy activation significantly improves the inflammatory response in sepsis. Histopathological sections showed that CLP destroyed the tight junctions between ileal epithelial cells, while autophagy induction reversed the damage. The sequencing results showed that autophagy activation increased the alpha diversity and alterted the composition and structure of gut microbiota. The abundance of Proteobacteria was markedly decreased in the Rap group, whereas Bacteroidetes was notably increased compared with the CLP group. Additionally, the protective effect of autophagy further changed the biomarkers in the microbial community. The top 35 functions in each sample were analyzed to obtain 18 genes including RNA synthesis, ATP binding and transport, chromosome assignment, osmotic polysaccharide transport, transcytosis, and methylation. <b>Conclusion:</b> Autophagy is able to improve inflammation and may directly or indirectly regulate the microbiota of septic rats. Autophagy may be an important target for future clinical interventions in the treatment of sepsis.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"9550301"},"PeriodicalIF":4.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of CXCR3 in Nervous System-Related Diseases.","authors":"Fangyuan Wang, Bing Guo, Ziyang Jia, Zhou Jing, Qingyi Wang, Minghe Li, Bingqi Lu, Wulong Liang, Weihua Hu, Xudong Fu","doi":"10.1155/2024/8347647","DOIUrl":"10.1155/2024/8347647","url":null,"abstract":"<p><p>Inflammatory chemokines are a group of G-protein receptor ligands characterized by conserved cysteine residues, which can be divided into four main subfamilies: CC, CXC, XC, and CX3C. The C-X-C chemokine receptor (CXCR) 3 and its ligands, C-X-C chemokine ligands (CXCLs), are widely expressed in both the peripheral nervous system (PNS) and central nervous system (CNS). This comprehensive literature review aims to examine the functions and pathways of CXCR3 and its ligands in nervous system-related diseases. In summary, while the related pathways and the expression levels of CXCR3 and its ligands are varied among different cells in PNS and CNS, the MPAK pathway is the core via which CXCR3 exerts physiological functions. It is not only the core pathway of CXCR3 after activation but also participates in the expression of CXCR3 ligands in the nervous system. In addition, despite CXCR3 being a common inflammatory chemokine receptor, there is no consensus on its precise roles in various diseases. This uncertainty may be attributable to distinct inflammatory characteristics, that inflammation simultaneously possesses the dual properties of damage induction and repair facilitation.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"8347647"},"PeriodicalIF":4.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effects of Baicalein on Lipopolysaccharide-Induced AR42J PACs through Attenuation of Both Inflammation and Pyroptosis via Downregulation of miR-224-5p/PARP1.","authors":"Ming-Wei Liu, Chun-Hai Zhang, Shou-Hong Ma, De-Qiong Zhang, Li-Qiong Jiang, Yang Tan","doi":"10.1155/2024/6618927","DOIUrl":"https://doi.org/10.1155/2024/6618927","url":null,"abstract":"<p><strong>Background: </strong>Baicalein has been used to treat inflammation-related diseases; nevertheless, its specific mechanism of action is unclear. Therefore, we examined the protective effects of baicalein on lipopolysaccharide-induced damage to AR42J pancreatic acinar cells (PACs) and determined its mechanism of action for protection.</p><p><strong>Methods: </strong>An <i>in vitro</i> cell model of acute pancreatitis (AP) was established using lipopolysaccharide (LPS) (1 mg/L)-induced PACs (AR42J), and the relative survival rate was determined using the 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) technique. Flow cytometry was applied to evaluate the apoptotic rates of AR42J PACs. The RNA and protein expression of miR-224-5p, poly ADP-ribose polymerase-1 (PARP1), nuclear transcription factor-<i>κ</i>B65 (NF-<i>κ</i>B65), phospho-kappa B alpha(p-I<i>κ</i>B-<i>α</i>), interleukin(IL)-18R, NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), gasdermin D (GSDMD), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1 was detected based on the WB and RT-PCR assays. IL-1<i>β</i>, IL-6, IL-18, and TNF-<i>α</i> expression levels in AR42J cells were measured via ELISA method. The cell morphology was examined using the AO/EB method.</p><p><strong>Results: </strong>The experiment confirmed a significant increase in the activity of AR42J cells treated with various doses of baicalein. Moreover, IL-1<i>β</i>, IL-6, TNF-<i>α</i>, and IL-18 expression levels in AR42J cells were dramatically reduced (<i>P</i>  < 0.05), while miR-224-5p level was obviously enhanced. The protein and gene expression of PARP1, NF-<i>κ</i>B65, p-I<i>κ</i>B-<i>α</i>, IL-18R, GSDMD, ASC, NLRP3, and caspase-1 was obviously decreased (<i>P</i> < 0.05). Apoptosis in AR42J cells was significantly reduced with significant improvement in cell morphology.</p><p><strong>Conclusion: </strong>Baicalein may significantly alleviate LPS-induced AR42J PAC damage by inhibiting the inflammatory response and pyroptosis. Its mode of action might be linked to higher miR-224-5p expression, which inhibits the PARP1/NF-<i>κ</i>B and NLPR3/ASC/caspase-1/GSDMD pathways.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"6618927"},"PeriodicalIF":4.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipocalin-2 Serum Levels in Rheumatoid Arthritis Patients Treated with Adalimumab and Its Correlation with Proinflammatory Factors.","authors":"Javier Conde-Aranda, Morena Scotece, María Varela-García, Carlos Torrijos-Pulpón, Laura Arosa, Miguel Camba-Gómez, Jesús Pino, Oreste Gualillo","doi":"10.1155/2024/7264704","DOIUrl":"https://doi.org/10.1155/2024/7264704","url":null,"abstract":"<p><strong>Background: </strong>Obesity is associated with an increased risk for different chronic diseases such as osteoarthritis (OA) or rheumatoid arthritis (RA). In fact, adipose tissue is now recognized as an endocrine organ able to secrete a wide variety of factors called adipokines, which have been demonstrated to participate in the pathophysiology of RA by regulating inflammation and immunity. LCN2 is one of these adipose tissue-derived factors. However, scarce information is available about the levels of this adipokine in different rheumatic diseases. Therefore, we aimed to analyze LCN2 serum levels in healthy, OA, and RA patients under different treatments.</p><p><strong>Methods: </strong>Serum levels of LCN2, among other proinflammatory and chemotactic factors, have been measured by ELISA or Multiplex in the following four groups of individuals: healthy, OA, and RA patients treated with conventional treatment or adalimumab.</p><p><strong>Results: </strong>We found increased serum levels of LCN2 in OA and RA patients. Interestingly, LCN2 serum levels show a similar pattern to that observed for different proinflammatory and chemotactic factors, being increased in RA conventional treated patients in comparison to RA patients treated with adalimumab. Also, RA patients under conventional treatment revealed a positive and significant correlation between LCN2 and CCL2, CCL3, IL-8, IL-1<i>β</i>, IL-6, and CRP. In patients with RA treated with adalimumab, only IL-6 and CRP correlated significantly with LCN2.</p><p><strong>Conclusions: </strong>Our results clearly suggest that LCN2 is modulated and associated with inflammation in rheumatic diseases. Therefore, the serum levels of this adipokine might be used as an additional biomarker of the inflammatory/disease activity.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"7264704"},"PeriodicalIF":4.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutathione: A Key Regulator of Extracellular Matrix and Cell Death in Intervertebral Disc Degeneration.","authors":"Fudong Li, Shaofei Li, Yangyang Shi, Feng Lin, Lining Rui, Jiangang Shi, Kaiqiang Sun","doi":"10.1155/2024/4482642","DOIUrl":"https://doi.org/10.1155/2024/4482642","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IVDD) is a degenerative disease accompanied by the loss of nucleus pulposus cells and the degradation of extracellular matrix (ECM), which tends to be associated with lower back pain. The ECM and various types of cell death in IVDD are regulated by multiple factors, such as inflammatory responses and oxidative stress. The glutathione (GSH) redox system is the most important antioxidant defense system in cells. GSH is one of the most abundant thiol antioxidants in mammalian cells, which functions directly and indirectly by scavenging peroxides through the GSH redox system. In these reactions, GSH is oxidized by electrophilic substances, such as reactive oxygen species and free radicals, to form glutathione disulfide to exert antioxidative effects. It has been reported that GSH can protect cells against the damage of oxidative stress and various pathophysiological stimulus that can lead to different types of cell death. In addition, it was reported that the level of GSH widely participates in apoptosis, autophagy, ferroptosis, and oxidative stress in many diseases including osteoarthritis and IVDD. Therefore, we summarized the effects of GSH on ECM metabolism and cells' functions during IVDD. In addition, we summarized the regulatory effects of small molecule compounds on GSH to explore potential ways to regulate the level of GSH. Better understanding the underlying role of GSH in regulating IVDD will facilitate the goal of preventing and retarding the progress of IVDD in the future.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"4482642"},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aloperine Ameliorates Acetaminophen-Induced Acute Liver Injury through HMGB1/TLR4/NF-<i>κ</i>B and NLRP3/Inflammasome Pathway.","authors":"Hui Chen, Shu Wang, Qiuyue Chen, Wen Yu, Hao Nie, Lian Liu, Bing Zheng, Quan Gong","doi":"10.1155/2024/3938136","DOIUrl":"https://doi.org/10.1155/2024/3938136","url":null,"abstract":"<p><strong>Purpose: </strong>Aloperine (ALO), an alkaloid isolated from <i>Sophora alopecuroides</i> L., possesses multiple pharmacological activities and holds a promise potential for the treatment of various clinical conditions, including skin hypersensitivity, cancer, and inflammatory disorders. The purpose of this study was to investigate the role of ALO in acetaminophen (N-acetyl-para-aminophenol (APAP))-induced acute liver injury and its underlying mechanisms.</p><p><strong>Materials and methods: </strong>An animal model of acute liver injury was induced by intraperitoneal injection of APAP (150 mg/kg). Prior to APAP injection, ALO (40 mg/kg) was administered daily for 7 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels were then measured using an automated chemical analyzer. Histopathological changes were evaluated using hematoxylin and eosin staining. Oxidative stress levels were measured by detecting superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA). Pro-inflammatory cytokines were detected in serum and liver tissues using ELISA and quantitative real-time polymerase chain reaction (q-PCR). The expression of members of the HMGB1/TLR4/NF-<i>κ</i>B signaling pathway and NLRP3 inflammasome were determined by Western blot and/or q-PCR. In addition, the expression and location of NLRP3, cleaved caspase-1, high-mobility group box 1 (HMGB1), and phosphorylated p65 (p-p65) were detected by immunofluorescence.</p><p><strong>Results: </strong>Pretreatment with ALO significantly protected mice from APAP-induced acute liver injury, with decreased MDA content, and significantly increased GSH and SOD activities. Furthermore, ALO pretreatment reduced the release of pro-inflammatory cytokines (IL-1<i>β</i> and TNF-<i>α</i>) and decreased the expression of caspase-1, cleaved caspase-1, and NLRP3. In addition, ALO pretreatment also inhibited the activation of the HMGB1/TLR4/NF-<i>κ</i>B signaling pathway.</p><p><strong>Conclusion: </strong>Taken together, ALO can ameliorate APAP-induced acute liver injury by inhibiting oxidative stress, inflammation by inhibiting the HMGB1/TLR4/NF-<i>κ</i>B, and NLRP3/inflammasome pathway.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"3938136"},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophages Promote Atherosclerosis Development by Inhibiting CD8T Cell Apoptosis.","authors":"Xiaoming Xu, Yuteng Wu, Yifei Xu, Wei Mao, Yanyun Pan","doi":"10.1155/2024/1929766","DOIUrl":"https://doi.org/10.1155/2024/1929766","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis is an inflammatory cardiovascular disease. However, whether the association of immune cells in plaques promotes the progression of this disease has not yet been completely elucidated.</p><p><strong>Materials and methods: </strong>Thus, this study aimed to investigate the relationship between C1q+ macrophages and CD8T cells through scRNA-seq data reanalysis, quantitative real-time PCR, and flow cytometry. Chromatin immunoprecipitation-quantitative polymerase chain reaction, western blot, and antibody-blocking experiments were performed to investigate the role of macrophage-CD8T interaction in atherosclerosis. An atherosclerotic mouse model was developed to confirm our findings.</p><p><strong>Results: </strong>Mechanistically, Spi1 expression induced by granulocyte-macrophage colony-stimulating factor promoted C1q expression in the macrophages. Moreover, C1q+ macrophages suppressed CD8T cell apoptosis by upregulating Slc7a7 expression to enhance the L-arginine uptake of CD8T cells. CD8T-derived interferon-<i>γ</i> promoted macrophage activation to induce atherosclerosis. Blockade of the C1q-C1qbp axis attenuated atherosclerosis.</p><p><strong>Conclusion: </strong>In conclusion, macrophages interacting with CD8T promote atherosclerosis development via the C1q-C1qbp axis.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"1929766"},"PeriodicalIF":4.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LIPS and PaO₂/FiO₂ Combined Plasma Biomarkers Predict Onset of Acute Respiratory Distress Syndrome in Patients of High Risks in SICU: A Prospective Exploratory Study.","authors":"Ziyuan Shen, Zhongnan Yin, Senhao Wei, Zhukai Cong, Feng Zhao, Hua Zhang, Xi Zhu","doi":"10.1155/2024/4936265","DOIUrl":"10.1155/2024/4936265","url":null,"abstract":"<p><strong>Objective: </strong>To explore and validate the value of clinical parameters combined with plasma biomarkers for predicting acute respiratory distress syndrome (ARDS) in patients of high risks in the surgical intensive care unit (SICU).</p><p><strong>Materials and methods: </strong>We conducted a prospective, observational study from January 2020 to December 2023, which enrolled 263 patients of high risks in the SICU of Peking University Third Hospital consecutively; they were classified as ARDS and non-ARDS according to whether ARDS occurred after enrollment. Collected clinical characteristics and blood samples within 24 hr of admission to SICU. Blood samples from the first day to the seventh day of SICU were collected from patients without ARDS, and patients with ARDS were collected until 1 day after ARDS onset, forming data based on time series. ELISA and CBA were used to measure plasma biomarkers. Endpoint of the study was the onset of ARDS. Cox proportional hazard regression analysis was used to find independent risk factors of the onset of ARDS, then constructed a nomogram and tested its goodness-of-fit.</p><p><strong>Results: </strong>About 84 of 263 patients ended with ARDS. Univariate analysis found 15 risk factors showed differences between ARDS and non-ARDS, namely, interleukin 6, interleukin 8 (IL-8), angiopoietin Ⅱ, LIPS, APACHEⅡ, SOFA, PaO₂/FiO₂, age, sex, shock, sepsis, acute abdomen, pulmonary contusion, pneumonia, hepatic dysfunction. We included factors with <i>p</i>  < 0.2 in multivariate analysis and showed LIPS, PaO₂/FiO₂, IL-8, and receptor for advanced glycation end-products (RAGE) of the first day were independent risk factors for ARDS in SICU, a model combining them was good in predicting ARDS (C-index was 0.864 in total patients of high risks). The median of the C-index was 0.865, showed by fivefold cross-validation in the train cohort or validation cohort. The calibration curve shows an agreement between the probability of predicting ARDS and the actual probability of occurrence. Decision curve analysis indicated that the model had clinical use value. We constructed a nomogram that had the ability to predict ARDS in patients of high risks in SICU.</p><p><strong>Conclusions: </strong>LIPS, PaO₂/FiO₂, plasma IL-8, and RAGE of the first day were independent risk factors of the onset of ARDS. The predictive ability for ARDS can be greatly improved when combining clinical parameters and plasma biomarkers.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"4936265"},"PeriodicalIF":4.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}