Archives of Medical Research最新文献

{"title":"Valdecoxib Ameliorates Apoptosis and Ferroptosis in Tenocytes via the SIRT6/NRF2-Mediated Suppression of Oxidative Stress","authors":"Wonjun Cho ,&nbsp;Do Su Lim ,&nbsp;Hyeon Ji Gwon ,&nbsp;A.M. Abd El-Aty ,&nbsp;Ji Hoon Jeong ,&nbsp;Tae Woo Jung","doi":"10.1016/j.arcmed.2025.103231","DOIUrl":"10.1016/j.arcmed.2025.103231","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Valdecoxib (VAL), a nonsteroidal anti-inflammatory drug (NSAID), is widely used in the treatment of osteoarthritis and rheumatoid arthritis. In addition to its anti-inflammatory properties, VAL has been shown to improve skeletal muscle insulin resistance and attenuate hepatic steatosis in obese individuals. However, its potential effects on oxidative stress injury in tenocytes remain unclear. This study aims to explore novel functions of VAL by investigating its impact on cell death in oxidative stress-exposed tenocytes and elucidating the underlying molecular mechanisms, with a focus on its therapeutic potential for the treatment of tendinopathy.</div></div><div><h3>Methods</h3><div>Apoptosis was assessed using cell viability assays, caspase-3 activity measurements, and TUNEL staining. Hydrogen peroxide (H₂O₂) and malondialdehyde (MDA) levels in tenocytes were quantified using appropriate assay kits, while reactive oxygen species (ROS) were detected by DCFDA staining. Tenocyte migration was evaluated using a scratch assay, and protein expression levels were analyzed by Western blotting.</div></div><div><h3>Results and Conclusion</h3><div>In the present study, we found that VAL treatment suppressed apoptosis and ferroptosis and normalized the expression of extracellular matrix (ECM) degradation markers, and enhanced cell migration in H₂O₂-treated tenocytes. VAL treatment increased the expression of SIRT6 and NRF2 and the activities of antioxidant enzymes. SIRT6-targeted siRNA abrogated the effects of VAL on tenocytes treated with H₂O₂. It also reduced VAL-induced NRF2 expression and antioxidant enzyme activities. These results suggest that VAL ameliorates oxidative stress induced tenocyte dysfunction through SIRT6/NRF2-mediated signaling. Therefore, this study highlights a potential therapeutic strategy for the treatment of overuse-induced tendinopathy.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 6","pages":"Article 103231"},"PeriodicalIF":4.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiosensitization Following Valproic Acid and Gamma Rays in Anaplastic Thyroid Cancer Cells Increases the Expression of hsa-miR-26a-5p","authors":"Marina Perona ,&nbsp;Cecilia Grissi ,&nbsp;Cinthia Rosemblit ,&nbsp;Leonardo Salvarredi ,&nbsp;Juan Pablo Nicola ,&nbsp;Lisa Thomasz ,&nbsp;María A. Dagrosa ,&nbsp;Graciela Cremaschi ,&nbsp;Hebe Durán ,&nbsp;Guillermo Juvenal ,&nbsp;Irene L. Ibañez","doi":"10.1016/j.arcmed.2025.103227","DOIUrl":"10.1016/j.arcmed.2025.103227","url":null,"abstract":"<div><h3>Background</h3><div>Anaplastic thyroid cancer (ATC) is a rare lethal human malignancy with a poor prognosis. Multimodality treatment, including radiotherapy, is recommended to improve local control and survival. Valproic acid (VA) is a clinically available anticonvulsant and histone deacetylase inhibitor with a well-documented side effect profile. Furthermore, VA radiosensitizes various cancer cells, including thyroid cancer. MicroRNAs (miRs) are deregulated in several cancers and may modulate radiation response. Therefore, the aim of this study was to analyze the effect of VA combined with gamma radiation in radioresistant ATC cells at the expression level of miRs.</div></div><div><h3>Methods</h3><div>ATC cells (8505c and KTC-2) were VA-treated and gamma-irradiated (2 Gy). The expression profile of miRs in 8505c was evaluated by microarray analysis 4 h after irradiation. Selected miRs were validated by RT-qPCR in both types of ATC cells.</div></div><div><h3>Results</h3><div>We observed that after combined VA and gamma irradiation treatment, 8505c cells showed 109 differentially expressed miRs as compared to irradiated cells alone. These miRs exhibited a radiosensitization profile highlighted by upregulation of hsa-miR-26a-5p, which is usually downregulated in aggressive thyroid cancers. Moreover, hsa-miR-27a-3p and hsa-miR-486–5p, which are often deregulated in thyroid neoplasms, were downregulated after irradiation and VA treatment, respectively. The expression level of these three miRs was validated in 8505c and KTC-2 cells after treatments.</div></div><div><h3>Conclusion</h3><div>The regulated miRs by VA and gamma irradiation reveal a novel miR expression profile with potential to be further studied in the radio-induced response and radiosensitization of ATC cells.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 6","pages":"Article 103227"},"PeriodicalIF":4.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Founder Variants in the Mexican Population: A Systematic Review","authors":"Sylvia Harari-Arakindji ,&nbsp;Teresa Metta-Harari ,&nbsp;Isabel Espino-Gutiérrez ,&nbsp;Lucia Taja-Chayeb ,&nbsp;Rodrigo González-Barrios ,&nbsp;Zyanya Lucia Zatarain-Barrón ,&nbsp;José Elias García-Ortiz ,&nbsp;Talia Wegman-Ostrosky","doi":"10.1016/j.arcmed.2025.103209","DOIUrl":"10.1016/j.arcmed.2025.103209","url":null,"abstract":"<div><h3>Background</h3><div>Founder variants (FVs) are genetic alterations inherited from a common ancestor that are frequently observed in genetically homogeneous populations. FVs significantly influence the prevalence of genetic disorders in specific populations; however, these variants have never been comprehensively described for the Mexican population.</div></div><div><h3>Aim</h3><div>This systematic review aimed to summarize and describe FVs of Mexican origin and their association with specific health conditions.</div></div><div><h3>Methods</h3><div>Studies were retrieved from the LILACS, COCHRANE, Scopus, and PubMed databases using a pre-specified search string. Information on genes, variants, and haplotypes that met the inclusion criteria was extracted from the articles. Based on the evidence provided, variants originating in the Mexican population were stratified according to whether they had strong or weak evidence for classification as FVs.</div></div><div><h3>Results</h3><div>A total of 32 studies were selected, describing 19 genes and 21 FVs. These include variants associated with a variety of diseases, such as Stargardt disease, breast and ovarian cancer, Fanconi anemia, congenital muscular dystrophy, and familial hypercholesterolemia. Haplotype analysis revealed that some variants, although frequent in the Mexican population, appear to be of European origin, as their haplotypes match those found in European populations and may represent variants introduced into Mexican territory following the Spanish conquest in the early 16th century.</div></div><div><h3>Conclusion</h3><div>These results provide a comprehensive view of the FVs present in the Mexican population, increasing our understanding of the genetic architecture in this region. In addition, they provide a broad context to elucidate potential associations between FVs and clinical, historical, and cultural findings.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 5","pages":"Article 103209"},"PeriodicalIF":4.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular disease in adolescents and young adults in Mexico: Secondary analysis of the 2021 global burden of disease study","authors":"Claudio A. Dávila-Cervantes","doi":"10.1016/j.arcmed.2025.103222","DOIUrl":"10.1016/j.arcmed.2025.103222","url":null,"abstract":"<div><h3>Background and Aims</h3><div>To analyse the burden of young-onset cardiovascular disease (CVD) in Mexico for the years 1990 and 2021, as well as trends from 1990 to 2021, and to evaluate its association with the sociodemographic index (SDI) and the Healthcare Access and Quality Index (HAQI).</div></div><div><h3>Methods</h3><div>A secondary analysis of data from the Global Burden of Disease (GBD) study was conducted, stratified by sex, age groups, states, and CVD subcauses. Metrics included mortality, years of life lost (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY).</div></div><div><h3>Results</h3><div>There was an increase in age-standardized young-onset CVD DALY rates in men and a decrease in women. The leading causes of young-onset CVD deaths were ischemic heart disease, and stroke. Males showed a higher burden for all CVD causes, except for rheumatic heart disease and pulmonary arterial hypertension. The burden of premature mortality was higher in men, while disability was more pronounced in women. Complex associations were observed between SDI, HAQI, and CVD burden, highlighting a heterogeneous situation among Mexican states.</div></div><div><h3>Conclusions</h3><div>Recognizing the unique cardiovascular profiles of young men and women and effectively engaging them in healthcare systems may lead to targeted interventions that reduce risk factors, improve health outcomes, and further decrease the burden of young-onset CVD in Mexico.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 6","pages":"Article 103222"},"PeriodicalIF":4.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of IL-17a on Apoptosis and Mucinosis-Related Molecules in the Microenvironment of Colorectal Cancer","authors":"Ali Ghorbani Ranjbary ,&nbsp;Jalil Mehrzad ,&nbsp;Hesam Dehghani ,&nbsp;Saman Hosseinkhani","doi":"10.1016/j.arcmed.2025.103220","DOIUrl":"10.1016/j.arcmed.2025.103220","url":null,"abstract":"<div><h3>Background/Aims</h3><div>IL17-producing Th17 represent a distinct subset of T-cells. The link between IL-17a and the colorectal cancer (CRC) microenvironment has been widely accepted. However, the role of IL-17a in epithelial cell apoptosis, autophagy, mucinosis, ultrastructural changes, and their potential correlations with CRC remains unclear.</div></div><div><h3>Materials and Methods</h3><div>Out of 2890 patients with CRC, 200 were divided into four groups (stage I-IV) and 50 into non-CRC/healthy/control. We investigated the relationship between IL-17a, apoptosis, autophagy, and mucinosis in patients with stage I-IV CRC (<em>in vitro/vivo</em>). In addition to many (para)clinical assessments, IL-17a load in blood and the tumor microenvironment (TME) in patients with CRC were assessed. To examine these associations, the effect of IL-17a on CRC cells was evaluated using qPCR, Western blotting, ELISA, bioluminescence, flow cytometry, and immunohistochemistry (IHC), and ultrastructural changes in the colonic epithelia were assessed by scanning and transmission electron microscopy.</div></div><div><h3>Results</h3><div>IL-17a is overexpressed in stage I–IV in the TME and in stage III–IV in the blood of patients with CRC. IL-17a upregulated apoptosis (caspases, cytochrome <em>c</em> (CYC), higher Bax:Bcl2 ratio), autophagy (SIRT1 and LC3), and the cell cycle (TP53, APC-1) and downregulated B3GALNT2 and mucins and led to morphological and nuclear changes in CRC epithelia.</div></div><div><h3>Conclusions</h3><div>IL-17a is abundantly expressed in the CRC microenvironment, and IL-17a-IL-17aR interactions play a critical role in the control of apoptosis and mucinosis. The observed remarkable association of IL-17a and apoptosis in adenocarcinoma provides valuable insight into the clinical implications of Th17/IL-17 in CRC.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 5","pages":"Article 103220"},"PeriodicalIF":4.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Tumor-Induced Mesenchymal Stem Cells on Cell Growth and Development in Different Cancer Types In Vitro and In Vivo Models","authors":"Mashael S. Altoub ,&nbsp;Amal S. Alhamid ,&nbsp;Badr Aldahmash ,&nbsp;Ahmed Rady ,&nbsp;Abdel Halim Harrath ,&nbsp;Ahmed HK. El-Hashash ,&nbsp;Pathalam Ganesan ,&nbsp;Savarimuthu Ignacimuthu","doi":"10.1016/j.arcmed.2025.103212","DOIUrl":"10.1016/j.arcmed.2025.103212","url":null,"abstract":"<div><h3>Background</h3><div>Mesenchymal stem cells (MSCs) are present in almost all tissue types. They have multipotent properties and unique abilities to self-renew and differentiate into various cell types. We evaluated the effect of MSCs pretreated with tumor factors on three different types of common, difficult to detect cancers using several cell-based assays such as cell viability and proliferation assay, scratch assays, migration assays, and <em>in vivo</em> assays.</div></div><div><h3>Methods</h3><div>We co-cultured each type of these common cancers with either control MSCs (control TERT-GFP cells) or MSCs that were pretreated with tumor factors (conditioned medium [CM]- induced TERT-GFP cells) and compared changes in cell morphology and growth, cell proliferation, cell migration, and colony formation in an <em>in vitro</em> model. Moreover, we examined the changes in these cancers after injection with control TERT-GFP cells (untreated) and CM- induced TERT-GFP cells in an <em>in vivo</em> model.</div></div><div><h3>Results</h3><div>We detected an increase in cell proliferation of each cancer cell line when co-cultured with normal MCSs. Only HT-29 colorectal adenocarcinoma cells co-cultured with CM-induced TERT-GFP cells showed a significant reduction in cell proliferation. We observed that pre-exposure of MSCs to tumor factors decreased the attraction/migration of MSCs towards all studied tumor cell types, particularly HT-29 cells. MSCs pre-exposed to tumor factors that were co-cultured with tumor cells significantly influenced the wound healing of these cells and tumor factors markedly decreased colony formation in colorectal cancer cells.</div></div><div><h3>Conclusions</h3><div>Our results suggest that coculture of MSCs with tumor factors for 1 wk can suppress cancer cells, especially colorectal cancer cells.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 5","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viewpoint: Differential Impacts of Acute and Long-Term Pollution Exposure on Cardiovascular Health","authors":"Sameer Mehta,&nbsp;Yashendra Sethi,&nbsp;David Zerpa,&nbsp;Nataly Rendon","doi":"10.1016/j.arcmed.2025.103213","DOIUrl":"10.1016/j.arcmed.2025.103213","url":null,"abstract":"","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 5","pages":"Article 103213"},"PeriodicalIF":4.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Major Histocompatibility Complex Class I and II Allele Frequencies and Disease Associations in Mexicans: A Systematic Review and Meta-Analysis","authors":"Anahi Pérez-Galicia ,&nbsp;Cesar Lugo-Caballero ,&nbsp;Santiago Martínez-Calvillo ,&nbsp;Vianey Ortiz-Navarrete ,&nbsp;Rebeca G. Manning-Cela","doi":"10.1016/j.arcmed.2025.103201","DOIUrl":"10.1016/j.arcmed.2025.103201","url":null,"abstract":"<div><h3>Background</h3><div>The major histocompatibility complex (MHC) plays a crucial role in immune responses and is associated with disease susceptibility. This study systematically reviews MHC class I and class II allele frequencies and their associations with diseases in the Mexican population from 1979 to 2023.</div></div><div><h3>Methods</h3><div>A systematic review following PRISMA guidelines was conducted. Reports were obtained from the Allele Frequency Net Database and PubMed using keywords related to HLA and Mexican populations. A total of 776 reports were screened, and 214 were retained for final analysis. Seventy-six studies comprising allele frequency data from over 20,000 individuals across Mexican states and indigenous communities were analyzed. In addition, over 138 articles were examined to identify alleles associated with various diseases.</div></div><div><h3>Results</h3><div>The analysis identified 117 alleles whose frequencies varied regionally within Mexico. While DPA1*01, DPB1*04:01, and DQA1*03 were predominant, DRB1*04, DQB1*03, and DQA1*05 were also prominent but variable. Certain alleles, such as A*02, B*35, C*04, and C*07, were relatively common in the population. Numerous disease correlations were uncovered, such as B*27′s strong association with spondyloarthropathies. DRB1*15:01 and DRB1*04 conferred an increase in multiple sclerosis, while DRB1*04 may protect against some skin diseases.</div></div><div><h3>Conclusion</h3><div>This review improves the understanding of MHC allele frequencies and disease associations in Mexicans, highlighting genetic diversity. The findings lay the groundwork for future research on genetic predispositions and health outcomes, aiding healthcare strategies in this diverse population. Further studies are needed to address data gaps and refine genetic profiles for targeted medical applications.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 5","pages":"Article 103201"},"PeriodicalIF":4.7,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785295","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":"West-Central African Ancestry of the Repeat-Expansion Founder Mutation on the JPH3 Gene in Mexican Patients With Huntington's Disease-Like 2","authors":"Miguel Ángel Ramírez-García ,&nbsp;Petra Yescas-Gómez ,&nbsp;Julio César Misael Monroy-González ,&nbsp;María Teresa Villarreal-Molina ,&nbsp;Karina Díaz-Barba ,&nbsp;Luis Rodrigo Macias-Kauffer ,&nbsp;Gabriela Castañeda-López ,&nbsp;Sandra Romero-Hidalgo","doi":"10.1016/j.arcmed.2025.103208","DOIUrl":"10.1016/j.arcmed.2025.103208","url":null,"abstract":"<div><h3>Background</h3><div>A trinucleotide repeat expansion of the <em>JPH3</em> gene causes Huntington disease-like 2 (HDL2), clinically indistinguishable from Huntington's disease and is considered a disease unique to African and Afro-descendant populations. We identified five HDL2 families from the Costa Chica region of southern Pacific Mexico. Because the Mexican population is admixed, we aimed to determine the ancestral origin of the expansion and define the mutation-carrying haplotype using microarray genomic data.</div></div><div><h3>Methods</h3><div>Sixteen individuals (Nine symptomatic, three asymptomatic mutation carriers and four healthy non-carriers) were included. Global and local ancestry were estimated using whole-genome microarray data. Principal component and quadratic discriminant analysis (QDA) were used to infer the most likely origin of the haplotypes, complemented by the SMOTE-Tomek sampling strategy.</div></div><div><h3>Results</h3><div>Mean ancestry proportions were 16.26, 27.33, and 56.39% for African, European, and Native American components, respectively. A 1.1 Mb segment inferred as African flanking the <em>JPH3</em> mutation locus was shared by at least one of the homologous chromosomes of all mutation carriers. Phased genotype analysis revealed a common 746 Kb haplotype containing the mutation that includes 412 SNPs. This shared haplotype was consistently inferred to be of African origin. QDA classified this haplotype as Yoruba in 78.3% of the resampling iterations.</div></div><div><h3>Conclusions</h3><div>Ancestry analysis suggests that the <em>JPH3</em> repeat expansion identified in our patients is a founder mutation of African origin. Other founder mutations causing rare genetic diseases in Mexico show how the admixture process in Latin America has contributed to the high prevalence of disease in certain geographical regions.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 5","pages":"Article 103208"},"PeriodicalIF":4.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Insights Into Early Detection and Progression of Knee Osteoarthritis: Unveiling Molecular Signatures","authors":"Bhavneet Kaur ,&nbsp;Diksha Rana ,&nbsp;Rinkle Sharma ,&nbsp;Monidipa Konar ,&nbsp;Mandeep S. Dhillon ,&nbsp;Devendra K. Chouhan ,&nbsp;Uttam Chand Saini ,&nbsp;Mahesh Prakash ,&nbsp;Amit Arora ,&nbsp;Indu Verma ,&nbsp;Jyotdeep Kaur ,&nbsp;Sadhna Sharma","doi":"10.1016/j.arcmed.2025.103206","DOIUrl":"10.1016/j.arcmed.2025.103206","url":null,"abstract":"<div><h3>Aim</h3><div>Osteoarthritis (OA) is the eleventh most disabling condition, with radiographic classification based on the Kellgren-Lawrence (KL) grading system. Early detection is critical to implement interventions to slow disease progression and improve patient outcomes. Proteomics, as a powerful strategy, could contribute to a better understanding of the disease pathophysiology and its early detection.</div></div><div><h3>Objectives</h3><div>The study aims to identify and confirm proteins associated with early detection and their role in the progression of knee OA.</div></div><div><h3>Methodology</h3><div>Synovial fluid (SF) and serum samples from the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, were categorized by KL classification and subjected to SWATH^TM analysis in the discovery phase. Seven samples of each OA grade were analyzed. A mass dynamics tool was used for data analysis and visualization. Significant protein expression level was defined as -1≤ log2FC ≥1 with p-value &lt; 0.05, and ELISA was used for validation in a greater number of patients.</div></div><div><h3>Results</h3><div>29 significantly modulated proteins were observed in osteoarthritis grade comparisons. Cathepsin G (CTSG) and angiotensinogen (AGT) were upregulated, whereas fumarylacetoacetase (FAH) and neural cell adhesion molecule 1 (NCAM1) were downregulated with radiographic disease progression, as validated by ELISA. CTSG, AGT, and NCAM1 showed good sensitivity and specificity in discriminating between early and late OA grades. Notably, serum and synovial fluid levels of AGT and NCAM1 exhibited significant correlation.</div></div><div><h3>Conclusion</h3><div>This is one of the first studies to comprehensively analyze proteins associated with OA progression. Additionally, the identified protein signatures have great potential for OA progression and differential diagnosis of early and late-stage OA.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 5","pages":"Article 103206"},"PeriodicalIF":4.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143740025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}