Annals of clinical and laboratory science最新文献

{"title":"Hsp90β1 Regulates Pyroptosis via the AMPK/mTORC1 Pathway to Alleviate Alveolar Epithelial Barrier Dysfunction in Acute Lung Injury.","authors":"Mengyan Chen, Xia Chen, Bin Fang, Mingxia Ji","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Acute lung injury (ALI) is a severe and potentially life-threatening inflammatory disorder of the lungs. Given the limited efficacy and significant side effects of current treatments for ALI, there is an urgency for novel therapeutic strategies.</p><p><strong>Methods: </strong>Potential pathogenic factors related to the mTOR complex 1 (mTORC1) pathway in ALI were identified through public database mining. <i>In vivo</i> and <i>in vitro</i> models of ALI were constructed through lipopolysaccharide induction. A549 cells were transfected with the constructed si-Hsp90β1, and AMPK activity in cells was inhibited using dorsomorphin. Hematoxylin-eosin (HE) staining, ELISA, lung wet/dry weight (W/D) ratio, and protein content in bronchoalveolar lavage fluid were employed to verify the successful establishment of the ALI animal model. The percentage of Caspase-1 positive cells was determined by the flow cytometry. The expression of Caspase-1 p20 in cells was quantified by immunofluorescence. Expression levels of Hsp90β1, epithelial barrier-related proteins (E-cadherin, ZO-1, and Occludin), pyroptosis-related proteins (Caspase-1, Caspase-1 p20, NLRP3), and proteins related to the AMPK/mTORC1 pathway were detected by western blot.</p><p><strong>Results: </strong>Through bioinformatics analysis, seven hub genes were screened out, among which Hsp90β1 was selected for further investigation. Hsp90β1 was observed to be up-regulated in the ALI rat model, accompanied by significant histopathological changes, elevated lung W/D ratio, and increased levels of inflammatory factors observed in ALI rats. Both <i>in vitro</i> and <i>in vivo</i> models exhibited enhanced pyroptosis and impaired barrier. In addition, AMPK activity was inhibited and mTORC1 was activated in the ALI rat model. Inhibiting Hsp90β1 reduced inflammation and pyroptosis while restoring barrier function. However, further inhibition of AMPK activity reversed the effect induced by Hsp90β1 inhibition.</p><p><strong>Conclusion: </strong>Low expression of Hsp90β1 alleviates inflammation, suppresses pyroptosis, and restores epithelial barrier function in ALI through the AMPK/mTORC1 pathway.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 4","pages":"532-545"},"PeriodicalIF":1.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079488","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":"Exosomal miR-98-5p Derived from Bone Marrow Mesenchymal Stem Cells Alleviates Myocardial Infarction by Regulating Autophagy via Targeting E2F6.","authors":"Haifei Xu, Wei Zhang","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effect of exosomal miR-98-5p derived from bone marrow mesenchymal stem cells (BMSCs) on cardiomyocyte injury in acute myocardial infarction (AMI) and analyze its mechanism of action.</p><p><strong>Methods: </strong>An AMI model in rats was established via ligation of the left anterior descending (LAD) coronary artery. Cardiac systolic function was assessed via echocardiography. Histopathological alterations in myocardial tissue were evaluated by hematoxylin and eosin (HE) staining, while the extent of myocardial infarction was determined through triphenyltetrazolium chloride (TTC) staining. Serum levels of CK-MB, cTnT, and LDH were quantified through ELISA. An AMI cell model was established by subjecting H9C2 cardiomyoblasts to hypoxic conditions. Exosomes were isolated from BMSCs, and their effects on cardiomyocyte injury were investigated. Cellular autophagy levels were examined via western blot (WB). The regulatory interplay between miR-98-5p and E2F6 was validated via a dual-luciferase reporter (DLR) assay.</p><p><strong>Results: </strong>In comparison to the Sham group, myocardial tissue in rats with AMI exhibited significant structural damage, accompanied by reduced autophagic activity and reduced expression of miR-98-5p. In comparison to the AMI + phosphate-buffered saline (PBS) group, treatment with BMSCs-derived exosomes (BMSCs-exo) markedly improved cardiac function and further enhanced autophagy in AMI rats. <i>In vitro</i>, cells subjected to hypoxic conditions displayed diminished viability and proliferative capacity, increased apoptosis, impaired autophagy, and decreased miR-98-5p expression relative to the control group. However, administration of BMSCs-exo restored miR-98-5p expression, mitigated cellular injury, and promoted autophagic activity. Notably, these protective influences were reversed by the addition of the autophagy inhibitor 3-methyladenine (3-MA). DLR assays confirmed a direct regulatory interaction between miR-98-5p and E2F6. Suppression of miR-98-5p resulted in the upregulation of E2F6, thereby attenuating the reparative effects of BMSCs-exo on myocardial tissue and inhibiting autophagy.</p><p><strong>Conclusion: </strong>BMSCs-exo miR-98-5p ameliorates AMI-induced myocardial injury by regulating cardiomyocyte autophagy through targeting E2F6.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 4","pages":"481-495"},"PeriodicalIF":1.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079506","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":"Regulatory Effect of the HMGB1-TLR4 Signaling Pathway in Pulmonary Ischemia/Reperfusion.","authors":"Zhaowang Tan, Yunyun Mao, Jianfeng Tu","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>To determine the molecular mechanism of pulmonary ischemia-reperfusion (I/R) injury and seek effective therapeutic targets to reduce the incidence and mortality of pulmonary I/R injury.</p><p><strong>Methods: </strong>Two models were established to explore the expression of the HMGB1-TLR4 pathway in a pulmonary I/R injury, its correlation with downstream inflammatory factors, and the effects of HMGB1-neutralizing antibodies on inflammation.</p><p><strong>Results: </strong>IL-6 and TNF-α levels in the three mouse models showed a rapid increase, IL-1β, IL-6, and TNF-α were up-regulated in alveolar macrophages after LPS stimulation, TNF-α and HMGB1 were up-regulated in TLR4+/+ cells and peaked at 48 h but was not up-regulated in TLR4-/- cells. Western blot assays revealed that in TLR4+/+ cells, TLR4 was up-regulated after stimulation by LPS and was rapidly down-regulated after treatment with the HMGB1-neutralizing antibody. In contrast, TLR4-/- cells did not respond to LPS stimulation, and the HMGB1-neutralizing antibody did not significantly alter the TLR4 concentration.</p><p><strong>Conclusions: </strong>HMGB1-TLR4 pathway plays an important role in the regulation of inflammation in pulmonary I/R injury. Furthermore, HMGB1 up-regulated downstream inflammatory factors via TLR4. HMGB1-neutralizing antibodies had a protective effect against lung injury by down-regulating the inflammatory response.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 4","pages":"496-505"},"PeriodicalIF":1.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079615","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":"Evaluation of Analytical Performance and Reference Interval of Abbott Thyroglobulin (Tg) Chemiluminescent Microparticle Immunoassay (CMIA) in a Chinese Population.","authors":"Jianfen Xu, Jiaoli Chen, Xiaowei Wang, Junhan Zhao, Yan Zhu, Jiansheng Huang","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Accurate measurement of thyroglobulin (Tg) is crucial for managing patients with differentiated thyroid cancer (DTC). This study aims to verify the analytical performance of the Abbott Tg assay and establish Tg reference intervals in an apparently healthy Chinese population.</p><p><strong>Methods: </strong>Analytical performance was evaluated in terms of precision, detection capabilities, and linearity. A method comparison with the Roche Tg assay was conducted using Passing-Bablok regression and Bland-Altman analysis. Reference intervals were established using serum Tg levels measured by the Abbott Alinity system in 1,081 healthy volunteers, categorized by age and gender.</p><p><strong>Results: </strong>Repeatability (CV%) for Tg at 0.96 and 7.53 ng/mL was 1.7% and 1.44%, respectively. Within-laboratory imprecision (CV%) at these concentrations were 2.17% and 1.61%. All test results (100%) were at or below the claimed limits of blank (LoB) and detection (LoD), exceeding the 85% threshold for the critical value observation ratio. The CV for the limit of quantification (LoQ) was 6.94%. Passing-Bablok and Bland-Altman analyses for Abbott vs. Roche Tg assays revealed a y-intercept of 0.025, a slope of 0.981, and a Spearman rank correlation coefficient of 0.993 (<i>P</i><0.0001), with a negative bias of -3.7%. Reference intervals were set between 0.22 and 53.30 ng/mL (2.5^th-97.5^th percentile). Gender had no impact on Tg levels while significant differences were found across different age groups (<i>P</i>=0.008).</p><p><strong>Conclusion: </strong>The Abbott Tg assay demonstrates verified analytical performance as per the manufacturer's claims. Reference intervals were established for an apparently healthy Chinese population, highlighting the significant influence of age on serum Tg levels.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 4","pages":"577-584"},"PeriodicalIF":1.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079471","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":"A Novel AAAS Gene Mutation in Allgrove Syndrome: Case Report and Genetic Insights from a Chinese Xinjiang Girl.","authors":"Nuerai Shawutali, Bayixiati Qianman, Jun He, Jianati Nuerhayixia, Yusufu Akemu, Shuang-Li Qin, Shui-Xue Li","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Allgrove Syndrome (AS), also known as Triple A syndrome (AAAS) is a rare autosomal recessive disorder characterized by a triad of alacrima, achalasia of the cardia, and ACTH-resistant adrenocortical insufficiency. The study aimed to broaden the understanding of AS's pathogenesis and clinical presentations within the Chinese population by identifying a novel mutation in the AAAS gene through genetic analysis.</p><p><strong>Case report: </strong>A four-year-old girl presented with short stature and recurrent vomiting for over two years. She had never been able to produce tears. Her physical examination showed short stature, undernourishment, dark pigmented dry skin, and reduced subcutaneous fat. The absence of lacrimal gland function was confirmed, and a barium meal test indicated a diagnosis of cardia achalasia. The patient was diagnosed with AS after genetic testing revealed a homozygous mutation, c.904_905delinsG, in exon 9 of the AAAS gene. Both parents were identified as carriers of the mutation, each presenting as heterozygous. Symptomatic supportive care was provided, including anti-inflammatory, hemostatic, acid-suppressive, antispasmodic, and rehydration therapies. A laparoscopic Heller myotomy was performed, which involved incising the muscular layer of the cardia and a gastric fundoplication. Postoperatively, the patient showed smooth feeding, upper gastrointestinal contrast barium passed without obstruction. The patient showed significant improvement and was discharged. The proband's sister was diagnosed with adrenal insufficiency based on hormonal levels and imaging.</p><p><strong>Conclusions: </strong>Genetic testing is instrumental in diagnosing AS, and prompt diagnosis can significantly enhance the quality of life for affected children. The study documented a novel mutation in AS, extending the diversity of known genetic variants. For patients with esophageal achalasia, the choice between balloon dilation and laparoscopic Heller's surgery should be individualized. Early identification and management of AS can significantly benefit affected children.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 4","pages":"618-624"},"PeriodicalIF":1.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079500","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":"Implementation of New Guidelines for Postpartum Glucose Tolerance Testing in Gestational Diabetes.","authors":"Nazmin Bithi, Ridwan B Ibrahim, Kesha Rector, Rachna Gandhi, Audra E Timmins, Mark Turrentine, Sridevi Devaraj","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Gestational diabetes mellitus (GDM) significantly increases the risk of type 2 diabetes mellitus (T2DM) in both mothers and offspring. Although a two-hour oral glucose tolerance test (OGTT) is advised postpartum, adherence remains poor. Our institution has reported suboptimal adherence (<30%) when testing is deferred to 1-3 months postpartum. In May 2024, the American College of Obstetricians and Gynecologists (ACOG) released updated guidance stating that offering a 75g OGTT during delivery hospitalization in the immediate postpartum period is a reasonable alternative to improve screening. This study evaluates the implementation of the updated guideline and examines early outcomes of inpatient postpartum OGTT over a six-month period.</p><p><strong>Methods: </strong>Postpartum patients with GDM received a 75g two-hour OGTT during delivery hospitalization, with samples drawn at zero and 120 minutes. Nursing and phlebotomy teams coordinated logistics to ensure test completion. Data were retrospectively reviewed.</p><p><strong>Results: </strong>Among 196 eligible patients, 184 (93.9%) completed testing. Of those tested, 24 (13.0%) had abnormal glucose values. Reported barriers included patient refusal, discharge timing, and existing hyperglycemia.</p><p><strong>Conclusion: </strong>Offering inpatient OGTT led to improved screening adherence and detection of abnormal glucose tolerance. This model may enhance postpartum diabetes prevention efforts in high-risk populations.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 4","pages":"567-571"},"PeriodicalIF":1.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079530","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":"Comparison of <i>Chlamydia pneumoniae</i>-specific T Effector Memory Lymphocytes in Asthmatic and Non-Asthmatic Adults.","authors":"Tamar A Smith-Norowitz, Sarah Shidid, Haram Abdelmajid, Nutchaya Amornruk, Wefag Ahmed, Yitzchok M Norowitz, Yecheskel Gold, Stephan Kohlhoff","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong><i>Chlamydia pneumoniae</i> is a gram-negative intracellular bacterium that causes respiratory infections, and may contribute to inflammation in asthma. Studies in our laboratory demonstrated that T lymphocyte/cytokine responses to <i>C. pneumoniae</i> in children with asthma were significantly higher, compared with non-asthma, which may indicate the presence of T effector memory (TEM) lymphocytes. In the present study, <i>C. pneumoniae</i> -specific TEMs and their intracellular cytokines were compared in asthmatic and non-asthmatic adults.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells (PBMC) (1×10⁶/mL) from asthmatic (N=6) and non-asthmatic (N=14) adults were infected for 24hr +/- <i>C. pneumoniae</i> TW-183 at a multiplicity of infection (MOI)=0.1 and cultured (48 hrs). Distributions of lymphocytes (CD3+, CD4+, CD8+) and TEM cells (CD4+CCR7-CD45RA+CD154+, CD8+CCR7-CD45RA+CD154+) were determined. Levels of intracellular Interleukin (IL)-2, IL-4, and Interferon (IFN)-gamma were measured (flow microfluorimetry).</p><p><strong>Results: </strong>Numbers of <i>C. pneumoniae</i>-stimulated CD3+CD4+CD45RO+CCR7-TEM (unstimulated, 1:10, 1:100) were higher in asthma compared with non-asthma (mean differences: unstimulated-stimulated) (-21±15, -17±15, -19±15; <i>P</i>=0.02, 0.04, 0.03, respectively) (Wilcoxon-signed rank test). However, CD3+CD4+IFN-gamma+TEMS (1:10, 1:100) were lower in asthma compared with non-asthma (mean differences: 2.2±5, 0.9±1; <i>P</i>=0.03, 0.04, respectively). When stratified according to <i>C. pneumoniae</i> IgG status, numbers of CD3+CD4+IL-2 (1:10) and CD3+CD4+IL-4+ (1:100) cells were higher in <i>C. pneumoniae</i> IgG+ compared with IgG- (mean differences: -0.2±0.2, -1.2±2.4; <i>P</i>=0.02. 0.05, respectively).</p><p><strong>Conclusion: </strong>Increased numbers of <i>C. pneumoniae</i> -stimulated TEM cells in asthma may indicate decreased effectiveness in clearing infection, suggesting an impaired IFN-gamma response.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 4","pages":"506-520"},"PeriodicalIF":1.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079536","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":"Falsely Low β-hCG Due to the Hook Effect in Twin Pregnancy with Hydatidiform Mole and Co-Existing Normal Live Fetus: A Case Report.","authors":"Ling Yang, Yingying Li, Bingyu Xue, Hong-Jian Xie, Wei Dai, Jia Mai","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Coexistence of hydatidiform mole (HM) and normal pregnancy in twin pregnancies is an extremely rare phenomenon. In HM, overproduction of human chorionic gonadotropin (β-hCG) by proliferating trophoblasts often results in extremely high serum β-hCG levels, which in turn causes a hook effect during the detection of β-hCG concentrations using immunochemiluminescent methods. This case highlights the critical role of serial dilution in mitigating hook effect-induced false-negative β-hCG results.</p><p><strong>Case report: </strong>This article reports a case of a 28-year-old woman presented to our hospital at 12 weeks' gestation with suspected HM and normal fetal coexistence. The patient became pregnant via <i>in vitro</i> fertilization procedure and showed a single gestational sac at 9 weeks' gestation. Unfortunately, at 13 weeks of gestation, the patient was diagnosed with twin pregnancy with HM and a co-existing normal live fetus. The pregnancy ended with a therapeutic abortion.</p><p><strong>Conclusions: </strong>Individualized diagnosis and treatment are important when HM coexists with a normal fetus. In such cases, we strongly recommend that ancillary tests be performed in addition to traditional imaging evaluation. In particular, the laboratory should be aware of false-negative β-hCG due to the hook effect.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 4","pages":"608-611"},"PeriodicalIF":1.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079539","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":"Identification and Validation of Mitochondria-Related Genes for Diagnosis of Early-Stage Sepsis.","authors":"Yanping Zhang, Yin Xu, Zeyu Huang, Jiahui Huo, Rui Sun, Xuecheng Tong","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Sepsis is a life-threatening condition with unclear pathogenesis and limited effective treatments. Mitochondrial dysfunction is considered a key factor in sepsis-induced multiple organ failure. This study aimed to identify essential mitochondria-related genes associated with sepsis to improve diagnosis and treatment strategies.</p><p><strong>Methods: </strong>High-throughput gene expression data (GSE185263) were analyzed to identify differentially expressed genes (DEGs) in 348 septic patients and 44 healthy controls. Mitochondria-related DEGs were screened using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Two machine-learning algorithms, LASSO and SVM-RFE, were applied to identify mitochondria-associated hub genes.</p><p><strong>Results: </strong>We identified 548 DEGs and screened 18 mitochondria-related DEGs. LASSO and SVM-RFE analyses identified 11 genes associated with sepsis diagnosis, showing strong diagnostic abilities through ROC assays. The expression of these 11 genes was examined by quantitative real-time polymerase chain reaction in septic patients and healthy participants, and differential expression of arginase 2 (<i>ARG2</i>), B-cell lymphoma 2-related protein A1 (<i>BCL2A1</i>), interferon alpha inducible protein 27 (<i>IFI27</i>), NADH: ubiquinone oxidoreductase subunit B3 (<i>NDUFB3</i>), stomatin (<i>STOM</i>), and translocator protein (<i>TSPO</i>) were observed. Some gene expression differences remained significant after adjusting for neutrophil and platelet counts.</p><p><strong>Conclusions: </strong>These findings suggest that mitochondrial dysfunction plays a critical role in sepsis progression, and the identified genes may serve as biomarkers for early diagnosis and targeted treatment, potentially improving patient outcomes.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 4","pages":"521-531"},"PeriodicalIF":1.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079549","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":"Microarray Identification of Differential lncRNA AC002454.1 Expression in Pediatric Acute Leukemia and Its Oncogenic Effect in Leukemia Cells <i>in vitro</i>.","authors":"Lan Cao, Xiaoshun He, Guixiong Gu, Yi Wang, Hailong He, Jun Lu, Peifang Xiao, Zhizhuo Du, Jian Pan, Shaoyan Hu","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>While long noncoding RNAs (lncRNAs) have emerged as critical regulators in hematological malignancies, their clinical significance in pediatric acute leukemia (AL) remains poorly characterized. This study aimed to (1) systematically profile differentially expressed lncRNAs (DE-lncRNAs) in pediatric AL through comparative analysis of bone marrow samples and (2) functionally characterize the oncogenic role of a top candidate, AC002454.1, to identify potential diagnostic markers and therapeutic targets.</p><p><strong>Methods: </strong>Using Arraystar Human LncRNA Array V3.0, we analyzed bone marrow samples from 43 pediatric AL patients (21 ALL, 22 AML) and 21 healthy donors. Key DE-lncRNAs were validated by qRT-PCR, with AC002454.1 selected for functional investigation. In NB4 leukemic cells, we performed (1) lentiviral knockdown of AC002454.1, (2) cell proliferation assays (CCK-8), (3) cell cycle analysis (PI staining/flow cytometry), (4) apoptosis assessment (Annexin V-FITC/PI dual staining), and (5) Western blot for CDK6 regulation.</p><p><strong>Results: </strong>Our qRT-PCR validation confirmed 97 differentially expressed lncRNAs (DE-lncRNAs), with lncRNA AC002454.1 showing the most significant differential expression between ALL and AML samples (<i>P</i>=0.040 and <i>P</i>=0.002, respectively, and particular elevation in AML). Functional studies demonstrated that AC002454.1 knockdown in NB4 cells led to (1) reduced cellular viability, (2) G2/M phase cell cycle arrest, and (3) increased apoptosis. Notably, AC002454.1 silencing also down-regulated CDK6 protein expression, suggesting a potential mechanistic link.</p><p><strong>Conclusions: </strong>We identified AC002454.1 as a functionally significant lncRNA in pediatric AL, demonstrating its oncogenic role through the promotion of proliferation and inhibition of apoptosis in leukemic cells. These findings suggest its potential as both biomarker and therapeutic target.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 4","pages":"546-555"},"PeriodicalIF":1.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079650","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}