Haiming Wen, Jun Liu, Chaona Wang, Shu Yan, Zhaoyu Li, Wei Lan, Hongtao Liu, Shaopeng Ming
{"title":"Molecular mechanisms of ferroptosis in renal ischemia-reperfusion injury Investigated via bioinformatics analysis and animal experiments.","authors":"Haiming Wen, Jun Liu, Chaona Wang, Shu Yan, Zhaoyu Li, Wei Lan, Hongtao Liu, Shaopeng Ming","doi":"10.1177/10815589241288518","DOIUrl":"10.1177/10815589241288518","url":null,"abstract":"<p><p>Kidney transplantation is a pivotal treatment for end-stage renal disease. However, renal ischemia-reperfusion injury (IRI) during surgery significantly impacts graft function. Despite unclear molecular mechanisms, no specific therapies or preventative measures are available. Gene expression profiles from renal biopsies before and after IRI were downloaded from public databases. Differentially expressed genes were identified using the Wilcoxon rank-sum test and weighted gene co-expression network analysis. Ferroptosis-associated genes were screened using the FerrDb database. The genes with the highest connectivity were identified via the protein-protein interaction (PPI) network and upstream regulatory miRNAs were found through the gene-miRNA network. A mouse renal IRI model was constructed for transcriptome sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) validation to elucidate the relationship between key ferroptosis genes and regulatory miRNAs in renal IRI. Differential analysis identified 15 ferroptosis-associated genes (<i>TNFAIP3</i>, <i>IL6</i>, <i>KLF2</i>, <i>EGR1</i>, <i>JUN</i>, <i>ZFP36</i>, <i>GDF15</i>, <i>CDKN1A</i>, <i>HSPB1</i>, <i>BRD2</i>, <i>PDK4</i>, <i>DUSP1</i>, <i>SLC2A3</i>, <i>DDIT3</i>, and <i>CXCL2</i>) involved in renal IRI regulation. In animal experiments, ferroptosis-related genes were also upregulated in the model group. Enrichment analysis and hematoxylin-eosin pathological staining suggested these genes are primarily involved in renal inflammatory responses. PPI network analysis revealed <i>IL6</i> as the gene with the highest connectivity, and the gene-miRNA network indicated <i>IL6</i> might be regulated by <i>miR-let-7a.</i> Animal experiments revealed decreased <i>miR-let-7a</i> and increased <i>IL6</i> levels in the model group, identifying potential therapeutic targets. <i>MiR-let-7a</i> regulates ferroptosis in renal IRI by targeting <i>IL6</i>, highlighting <i>IL6</i> as a crucial gene in the ferroptosis process of renal IRI.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"134-146"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kunkun Han, Xuan Wang, Guodong Chen, Wenyue Liu, Xiao Mei, Yili Yang, Xin Xu
{"title":"Targeted therapy of multiple myeloma by IL21-NKG2D CAR-T cells.","authors":"Kunkun Han, Xuan Wang, Guodong Chen, Wenyue Liu, Xiao Mei, Yili Yang, Xin Xu","doi":"10.1177/10815589241291846","DOIUrl":"10.1177/10815589241291846","url":null,"abstract":"<p><p>NKG2D chimeric antigen receptor (CAR)-modified T cells (NKG2D CAR-T cells) have been reported to be preclinically efficient in several tumors, but little is known whether NKG2D CAR-T cells co-expressing IL21 (IL21-NKG2D CAR-T cells) display greater antitumor activity in multiple myeloma (MM). In this study, the lentivirus has been produced for expression of the IL21 sequence linked to the extracellular NKG2D sequence with the signal peptide linked through the CD8α hinge-transmembrane domain to the 4-1BB molecule fused with the CD3-ζ chain signaling domain, and the engineered IL21-NKG2D CAR-T cells and NKG2D CAR-T cells were constructed. The CAR expression on CAR-T cells was assessed by flow cytometry, and the killing effects of CAR-T cells on MM were assessed by the cytotoxicity assay and ELISA assay. Moreover, xenograft models were also established to evaluate the ability of IL21-NKG2D-CAR-T cells to eliminate MM in vivo. Our results indicated that NKG2D CAR-T cells had dramatic cytotoxicity on MM cells in vitro, and co-expression of IL-21 significantly increased the cytotoxicity of NKG2D CAR-T cells on MM cells. Remarkably, we found that dexamethasone enhanced the cytotoxicity of IL21-NKG2D CAR-T cells on MM cells. Furthermore, IL21-NKG2D CAR-T cells also displayed significant anti-myeloma activity in vivo. In conclusion, IL21-NKG2D CAR-T cells had dramatic cytotoxicity on MM cells in vitro and in vivo, and a system to apply IL21-NKG2D CAR-T cells and low dosage of dexamethasone for the future study of the targeted therapy for MM has been established.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"45-53"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between acetaminophen and risk of mortality in patients with sepsis-associated acute kidney injury: A retrospective cohort study from the MIMIC-IV database.","authors":"Hui Yu, Ting Yang, Dongsong Liu","doi":"10.1177/10815589241290210","DOIUrl":"10.1177/10815589241290210","url":null,"abstract":"<p><p>The occurrence of sepsis-associated acute kidney injury (SA-AKI) predicts a worse prognosis. We aimed to assess the impact of acetaminophen use on short-term mortality in patients with SA-AKI. A total of 6563 patients diagnosed with SA-AKI from the 2008 to 2019 Medical Information Mart for Intensive Care IV (MIMIC-IV) database were enrolled in this retrospective cohort study. The Cox regression model was utilized to analyze the associations of acetaminophen with 30-day mortality and in-hospital mortality. Additional propensity score matching (PSM) analysis was performed regarding patients with acetaminophen use versus those without. Of these patients, 30-day mortality occurred in 1421 (21.65%) patients and in-hospital mortality in 1246 (18.99%) patients. Patients who used acetaminophen were associated with a reduced risk of 30-day mortality (hazard ratio (HR) = 0.80, 95% confidence interval (CI): 0.71-0.90) and in-hospital mortality (HR = 0.72, 95% CI: 0.63-0.82). The PSM analysis demonstrated that acetaminophen use was still related to a reduced risk of 30-day mortality and in-hospital mortality. Subgroup analysis showed that the relationships between acetaminophen and 30-day mortality and in-hospital mortality were consistent across subgroups (p < 0.05). The use of acetaminophen has an association with lower short-term mortality in patients with SA-AKI.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"125-133"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long COVID: A risk factor for anxiety, depression, and suicidality?","authors":"Neslihan Özçelik, Songül Özyurt, Elvan Şentürk Topaloğlu, Aziz Gümüş, Çiçek Hocaoğlu, Ünal Şahin","doi":"10.1177/10815589241261291","DOIUrl":"10.1177/10815589241261291","url":null,"abstract":"<p><p>In many COVID-19 survivors, symptoms continue for a long time. This study aims to examine the relationship between the long-term effects of COVID-19, levels of anxiety and depression, and suicidal ideation with sociodemographic factors and symptoms. A cross-sectional study was conducted on patients who came for control at least 3 months after having COVID-19 disease, in the stable period, and still have symptoms after COVID-19. Demographic characteristics, symptoms, The Beck Depression Scale (BDS), The Beck Anxiety Scale (BAS), and suicidal ideation were assessed with face-to-face questionnaires. A total of 490 patients participated in the study. Thirty percent of patients scored positive on the BDS and 46% scored high on the BAS. Female sex was found to be a risk factor. Anxiety and depression were found to be significantly associated with long COVID symptoms. Both BAS and BDS scores were significantly higher in people with suicidality compared to others, and long-term symptoms were found to be statistically associated with this situation. Depression and anxiety are common in cases of long COVID. It is important for healthcare professionals to be aware of these potential mental health consequences, especially suicidality, and to provide appropriate support and interventions for individuals with long COVID.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"67-74"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wanxiang Li, Yize Yan, Xinguang Cui, Jichao Bian, Long Yuan, Guodong Wang
{"title":"Exploring the association between hemoglobin, albumin, lymphocyte, and platelet score and all-cause mortality among middle-aged and older patients with osteoarthritis.","authors":"Wanxiang Li, Yize Yan, Xinguang Cui, Jichao Bian, Long Yuan, Guodong Wang","doi":"10.1177/10815589241273682","DOIUrl":"10.1177/10815589241273682","url":null,"abstract":"<p><p>Integrating hemoglobin, albumin, lymphocyte, and platelets (HALP) scores can simultaneously reflect systemic inflammation and nutritional status. Some evidence suggests its prognostic value in certain malignancies, however, the impact of HALP on individuals with osteoarthritis (OA) who are middle-aged and older remains unknown. This retrospective cohort study included 3566 individuals from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. The study endpoint was the all-cause mortality of OA patients. Weighted Cox models were used to assess the relationship between HALP score and all-cause mortality. Subgroup analyses stratified by age, gender, diabetes, dyslipidemia, and cardiovascular disease were conducted. After the follow-up was terminated, 920 participants experienced all-cause mortality, and 2646 participants survived. After adjusting for covariates, the continuous analysis revealed an inverse association between HALP score and all-cause mortality (hazard ratio (HR) = 0.89, 95% confidence interval (CI): 0.83-0.95). The categorical analysis indicated that the lowest quartile of HALP score was related to higher all-cause mortality by using the highest quartile of HALP score as a reference (HR = 1.46, 95% CI: 1.18-1.81). The association between HALP score with lowest quartile and all-cause mortality remained significant across different subgroups. This study suggested that HALP score was linked with all-cause mortality among middle-aged and older individuals diagnosed with OA, thereby indicating its potential as a reliable prognostic indicator for this patient population.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"94-103"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chenghao Chu, Yongwei Zhang, Ruiran Yu, Bin Liu, Bin Wang, Zhangxuan Xu, Kai Ling Chin
{"title":"MEF2A restrains cisplatin resistance in gastric cancer cells by modulating NFKBIA/NF-κB signaling pathway.","authors":"Chenghao Chu, Yongwei Zhang, Ruiran Yu, Bin Liu, Bin Wang, Zhangxuan Xu, Kai Ling Chin","doi":"10.1177/10815589241290199","DOIUrl":"10.1177/10815589241290199","url":null,"abstract":"<p><p>Cisplatin (DDP) resistance represents a pivotal contributing factor to chemotherapy failure and adverse patient outcomes in gastric cancer (GC). The objective of the present study was to investigate the roles and underlying mechanisms of myocyte enhancer factor 2A (MEF2A) in DDP resistance in GC. GC cell line AGS and MKN-45 cells were applied to construct DDP-resistant cells. CCK-8, colony formation, and flow cytometry methods were validated for determining the IC50 value of DDP and cell survival of GC cells. qRT-PCR and western blotting analysis quantified the molecular levels at mRNA and protein, respectively. Chromatin immunoprecipitation and dual-luciferase assays validated the molecular relationship between MEF2A and NF-κB inhibitor alpha (NFKBIA). Roles of MEF2A in in vivo were performed employing a xenograft model. The results showed that NFKBIA was greatly decreased in DDP-resistant AGS and MKN-45 cells compared to their respective parental cells. Increasing NFKBIA expression impaired the IC50 value of DDP and cell survival in DDP-resistant cells, while these alterations were rescued upon TNF-α treatment. Mechanistically, MEF2A acts as a transcriptional activator of NFKBIA, which led to the reduction of phosphorylation of p65 and cytoplasmic retention. Moreover, MEF2A overexpression promoted the sensitivity of GC cells to DDP and tumor growth, whereas these effects were partially reversed by NFKBIA silence. Collectively, MEF2A mitigated the DDP resistance in GC cells by modulatory actions on the NFKBIA/NF-κB signaling, shedding light on MEF2A/NFKBIA might be a promising intervention target for improving DDP resistance in GC.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"54-66"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Idris Akinlusi, Brian Kan, Ted Shi, Jose Barragan, Carlos Bouchot, Jorge Cervantes
{"title":"Human microglia polarization following infection with the Lyme disease spirochete.","authors":"Idris Akinlusi, Brian Kan, Ted Shi, Jose Barragan, Carlos Bouchot, Jorge Cervantes","doi":"10.1177/10815589241290206","DOIUrl":"10.1177/10815589241290206","url":null,"abstract":"<p><p>Infection with <i>Borrelia burgdorferi</i> can spread and cause central nervous system involvement, known as neuroborreliosis. Microglia phagocytose bacteria, mediate inflammation, and elicit an immune response toward the spirochete. Like other tissue macrophages, microglia can polarize into two different modulatory phenotypes, M1 and M2. We explored human microglial polarization changes upon infection with <i>B. burgdorferi</i>. HMC3 human microglia cell line was infected with <i>B. burgdorferi</i> for 24 h. Expression of polarization markers was evaluated via flow cytometry at 4 and 24 h. Secreted immunological mediators were evaluated using a multiplex ELISA system at 4, 18, and 24 h. An early decrease followed by a later increase in expression of M1 polarization marker iNOS was observed at 4 h, and 24 h, respectively. A decrease in M2 marker CX3CR1 occurred at 24 h. There were no changes in expression of M1 markers CD14, or in M2 markers CD163 and CD206. Multiplex ELISA evidenced an increase in secretion of activation markers MIP-1α, MIP- 1β, IP-10, chemotactic factor MCP-1, M1 polarization cytokine IL-8, and VEGF, at 4, 18, and 24 h. A decrease of iNOS at 4 h of infection suggests a diminished production of reactive nitrogen species that are a critical component of innate defense against infection. Increased iNOS and simultaneously decreased expression of CX3CR1 at 24 h, may suggest initiation of neuroprotective regulation of microglia recruitment to neuroinflammation. The dynamics of major inflammatory cytokines appear to be important in the microglial response to <i>B. burgdorferi</i> and should be further studied as these could become therapeutic targets in neuroborreliosis.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"172-178"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Short-term efficacy of moderate-intensity rosuvastatin in coronavirus disease 2019 patients: A randomized clinical trial.","authors":"Katayoun Rafsanjani, Amirhossein Ghaseminejad-Raeini, Alireza Azarboo, Samaneh Parsa","doi":"10.1177/10815589241279008","DOIUrl":"10.1177/10815589241279008","url":null,"abstract":"<p><p>As the coronavirus disease 2019 (COVID-19) pandemic persists, the exploration of adjunct therapies to mitigate disease severity remains a priority. Statins, known for their pleiotropic effects, have been under investigation for their potential role in managing COVID-19 complications. The study was conducted in a single referral hospital and adhered to Consolidated Standards of Reporting Trials guidelines. Eligible participants were randomized in a 1:1 ratio into either the rosuvastatin group or the control group. Outcome measures included vital signs, laboratory data, clinical outcomes, and patient symptoms. Statistical analysis was performed using SPSS software (version 26.0, IBM Corp., Armonk, New York). A total of 100 patients were enrolled. No significant differences were observed between the rosuvastatin and control groups in terms of baseline characteristics and laboratory parameters, except for the fact that rosuvastatin-treated patients showed lower levels of C-reactive protein in comparison with the controls on both the 1st and 5th days (38.1 ± 16.3 vs 50.5 ± 25.3) compared to the control group. Clinical outcomes, including hospital length of stay, intensive care unit admission, need for intubation, and 1-month mortality, did not differ significantly between the two groups. Symptom scales, as assessed by the Borg Rating of Perceived Exertion and Leicester Cough Questionnaire, showed significant improvement in the rosuvastatin group compared to controls. Our study provides insights into the short-term efficacy of moderate-intensity rosuvastatin in COVID-19 patients. Further research is warranted to elucidate the long-term effects and optimal dosing of statins in COVID-19 management.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"85-93"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matan Elkan, Lior Cochavi, Alla Khashper, Eli Kravchik, Ella Kravitz, Ronit Koren
{"title":"CT-based sarcopenia assessment: Predicting outcomes in acute infection patients.","authors":"Matan Elkan, Lior Cochavi, Alla Khashper, Eli Kravchik, Ella Kravitz, Ronit Koren","doi":"10.1177/10815589241280861","DOIUrl":"10.1177/10815589241280861","url":null,"abstract":"<p><p>In this retrospective cohort study, we investigated the prognostic value of sarcopenia evaluated by Computed Tomography (CT)-based indices for adverse hospitalization outcomes in patients with acute infections. We analyzed data from 225 patients admitted to the hospital for acute infections between 2019 and 2020. Patients who had undergone an abdominal CT scan either up to 1 month before or within the first 3 days of hospitalization were included. CT image analysis was used to evaluate skeletal muscle mass (by skeletal muscle index (SMI)) and muscle quality (by psoas muscle density, pMD). Low pMD was associated with higher in-hospital mortality (31% vs 11.4% p < 0.001) as well as higher longer-term mortality rates (p = 0.008 for 30 days and <0.001 for 90- and 1-year mortality). Low pMD remained an independent poor prognostic factor after controlling for confounders, with an adjusted odds ratio (aOR) of 2.74, (95% CI 1.33-5.67, p = 0.006) for 1-year mortality, and aOR of 2.61, (95% CI 1.23-5.55) for a prolonged hospital stay. Low SMI was associated with adverse outcomes, although this association was not independent after controlling for confounders. Notably, patients with both low SMI and pMD exhibited the poorest hospitalization outcomes: aOR for 1-year mortality 5.015 (95% CI 1.767-14.23, p = 0.002), and prolonged length of stay aOR 3.197, (95% CI 1.159-8.821, p = 0.025). CT-based muscle indices serve as independent prognostic factors in medical patients admitted with acute infection. Incorporating radiological assessments of sarcopenia into routine care for hospitalized patients with acute infection may enable risk stratification and early intervention in reversible conditions.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"116-124"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative analysis of compartment-specific immunothrombotic biomarker profiles in bronchoalveolar lavage fluid and serum of patients with pneumonia-related acute respiratory distress syndrome: A preliminary cross-sectional study.","authors":"Xiaolong Zong, Xuechao Wang, Yaru Liu, Xiao Wang, Duanyang Li, Zhiqing Zhou, Zhenyu Li","doi":"10.1177/10815589241288515","DOIUrl":"10.1177/10815589241288515","url":null,"abstract":"<p><p>Immunothrombosis has emerged as a potential mechanistic link underlying the development and progression of acute respiratory distress syndrome (ARDS), but understanding its specific profile in patients, both locally and systemically, is limited. The objective of this study was to characterize and compare the immunothrombotic signatures in patients diagnosed with pneumonia-related ARDS (p-ARDS) at both the pulmonary and systemic levels and to evaluate their clinical relevance. The study included 23 consecutive patients diagnosed with p-ARDS admitted to the intensive care unit at a tertiary university hospital from July 2022 to May 2023, alongside 40 concurrently hospitalized patients with common pneumonia as controls. Paired bronchoalveolar lavage fluid (BALF) and serum samples were collected from the participants for the analysis of 15 biomarkers to assess and quantify the pulmonary and systemic immunothrombotic signatures. The study results revealed significant pulmonary inflammation and systemic endothelial injury in p-ARDS patients compared to pneumonia controls. These observations were maintained after adjustment for severity of illness (Acute Physiology and Chronic Health Evaluation II scores). In terms of clinical relevance, inflammatory biomarkers (interleukin [IL]-6, IL-8) in BALF were found to correlate with PaO<sub>2</sub>/FiO<sub>2</sub> ratio, while serum levels of a disintegrin and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS-13) and thrombomodulin showed associations with Sequential Organ Failure Assessment and Disseminated Intravascular Coagulation scores. In conclusion, this preliminary investigation identified compartment-specific variations in the immunothrombotic signature between patients with p-ARDS and those with pneumonia alone, with inflammatory responses predominantly localized in the alveolar compartments and coagulation/endothelial injury biomarkers more pronounced in peripheral blood.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"104-115"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}