Diabetic nephropathy (DN) is a leading cause of end-stage renal disease, characterized by progressive kidney dysfunction. Early detection and targeted therapies remain key challenges in managing DN. This study aims to identify proteomic alterations in DN patients compared to healthy controls, focusing on proteins involved in inflammation, oxidative stress, immune response, and metabolic dysregulation. Using mass spectrometry and advanced bioinformatics, we identified significant upregulation of proteins associated with platelet activation, immune regulation, and extracellular matrix remodeling, as well as downregulation of proteins linked to lipid metabolism, immune regulation, and structural stability. These findings highlight the molecular complexity of DN and suggest that altered protein expression plays a critical role in the progression of kidney damage. The identified proteins may serve as potential biomarkers for early diagnosis and therapeutic targets for DN. Our results underline the importance of proteomic analyses in advancing the understanding of DN pathogenesis and in developing strategies for personalized treatment to improve patient outcomes. Future research should focus on further elucidating these molecular mechanisms and their implications for clinical management.

Introduction: Cholangiocarcinoma is an aggressive neoplasm of bile duct epithelial cells with poor prognosis due to limited treatment options. Fibroblast growth factor receptor 2 (FGFR2) is critical in cholangiocarcinoma by activating pathways such as MAPK/ERK and PI3K/AKT, marking it as a promising therapeutic target. This study aimed to identify natural FGFR2 inhibitors by using computational methods. Methods: 46 natural compounds were selected from PubChem based on favorable physicochemical properties and drug-likeness criteria. Molecular docking was performed using SwissDock against FGFR2 (PDB ID: 4J97). The top five compounds were further assessed for pharmacokinetics, pharmacodynamics, and toxicity via SwissADME, pkCSM, and DeepPK tools. Additionally, protein-protein interaction networks and pathway enrichment analyses were conducted using the STRING database and KEGG. Results: Docking analysis identified Rutecarpine, Palonosetron, Metribolone, 6-Ketoestradiol, and Gestrinone as the top FGFR2 inhibitors, with docking scores between – 6.34 and – 5.95 kcal/mol. ADMET predictions showed favorable drug- like properties, good bioavailability, and acceptable safety profiles. Network and pathway analyses confirmed FGFR2’s role in key oncogenic pathways, including MAPK, PI3K/AKT, and Ras. Conclusions: This study identified promising FGFR2 inhibitors, particularly Rutecarpine, as potential therapeutic candidates for cholangiocarcinoma, warranting further experimental validation.

Introduction: Primary Biliary Cholangitis (PBC) is an autoimmune liver disease characterized by chronic destruction of intrahepatic bile ducts, leading to fibrosis and eventual liver failure. Current first-line treatments, including ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), provide insufficient therapeutic benefit for a substantial proportion of patients. Integrative systems-level analyses of multi-omic data enable the identification of potential therapeutic targets and the repurposing of existing drugs. Methods: A total of 214 human genes associated with PBC were retrieved from NCBI Gene and DisGeNET databases. Protein-protein interaction (PPI) networks were constructed using STRING and subsequently analyzed for hub genes and network clusters using Cytoscape. Pathway enrichment analysis was performed using Reactome, and drug-gene associations were evaluated using the DSigDB database. Selected drug-target interactions were further assessed using experimentally validated binding data from BindingDB and molecular docking results generated by SwissDock. Results: The network analysis produced 187 nodes which connected through 1,645 edges. Hub gene analysis highlighted TP53, IL6, CXCL8, STAT3, IFNG, JUN, and CDKN1A as central regulators of immune and apoptotic signaling pathways. The Reactome analysis showed that interleukin and TP53-mediated pathways achieved statistical significance at an FDR value of less than 0.05. The FDA has approved six compounds for medical use including Simvastatin and Budesonide and Tocilizumab and N-acetylcysteine and PD98059 and Vorinostat which demonstrate supportive experimental or computational evidence of target engagement. Conclusion: This integrative network-based framework identified central molecular regulators and repurposable drugs for PBC. Further experimental and clinical studies are required to determine the therapeutic potential of these candidates in autoimmune liver disease.

Background: The atherogenic plasma index (AIP) has emerged as a promising marker reflecting the balance between triglyceride (TG)-rich lipoproteins and high-density lipoprotein cholesterol (HDL-C). However, its clinical utility in identifying atherogenic dyslipidemia (AD), particularly across sex and thyroid function subgroups, remains incompletely characterized. Objective: To compare the discriminatory performance of AIP and non-HDL-C for identifying AD in a large laboratory-based population, to evaluate this comparison across sex- and thyroid-status strata, and to explore thyroid-related and hematological patterns across AIP quartiles. Methods: This laboratory-based cross-sectional study included 76.743 adult individuals with complete lipid, thyroid, and hematological parameters retrieved from preexisting routinely collected laboratory information system records. Participants were stratified into AIP quartiles. The primary analysis was the receiver operating characteristic-based comparison of AIP and non-HDL-C for identifying AD. Secondary analyses included AIP quartile group comparisons, Spearman correlation analysis, and exploratory multinomial logistic regression. Results: AIP showed excellent discriminatory performance for identifying AD and outperformed non-HDL-C in the overall cohort (area under the curve 0.972 vs. 0.710). This stronger discriminatory performance was also observed across sex- and thyroid-status strata. Across AIP quartiles, lipid-related parameters showed the largest differences, particularly TG, HDL-C, and remnant cholesterol. Thyroid-related and hematological indices also differed across quartiles, but effect sizes were small. In exploratory multinomial regression models, age and male sex showed the most consistent associations with higher AIP quartile membership, whereas thyroid-related and hematological indices provided additional but limited explanatory information. Conclusions: AIP is a powerful and clinically practical marker for identifying AD, demonstrating superior and consistent performance compared with non-HDL-C across different clinical subgroups. Thyroid-related and hematological findings should be interpreted as exploratory rather than causal or biologically independent effects. Prospective multicenter studies are needed to validate generalizable AIP cutoff values and assess its added value beyond conventional lipid markers.

Osteoarthritis (OA) represents a degenerative joint disease which advances through cartilage breakdown, synovial inflammation, and subchondral bone transformation until it causes persistent pain and mobility loss. The scientific community lacks complete knowledge about OA disease mechanisms and post-operative healing processes despite arthroplasty surgery providing effective symptom relief. This study investigated plasma proteomic changes in OA patients before and after arthroplasty. The cohort included eight OA patients undergoing knee or hip arthroplasty and ten age-, sex-, and body mass index-matched healthy controls. Plasma proteins were analyzed using liquid chromatography–tandem mass spectrometry following enzymatic digestion and depletion of high-abundance components. The bioinformatic analysis together with quantitative methods showed that OA patients experienced changes in inflammatory pathways, extracellular matrix remodeling, immune system regulation and coagulation processes. A total of 93 proteins were differentially abundant in the pre-operative comparison. Among these, 63 proteins were consistently up-regulated and 23 were consistently down-regulated across both pre- and post-operative time points. In addition, 20 proteins exhibited post-operative-specific changes. These findings highlight both persistent disease-associated alterations and transient proteomic shifts linked to post-operative recovery. Overall, this study identifies candidate plasma proteomic signatures associated with OA and surgical intervention, providing exploratory insights into disease monitoring and potential personalized therapeutic strategies.

Amaç: Preanalitik hatalar, özellikle venöz kan alma sürecinde ortaya çıkanlar olmak üzere, laboratuvar tanısal yanlışlarının başlıca kaynağını oluşturur ve laboratuvar hatalarının önemli bir kısmından sorumludur. Bu hataların sistematik izlenmesi ve hedefe yönelik müdahalelerle azaltılması, laboratuvar kalitesini artırmanın ve hasta güvenliğini sağlamanın temel koşullarından biridir. Gereç ve Yöntem: Bu prospektif gözlem çalışması, bir üniversite hastanesinin merkezi kan alma biriminde 5 gün boyunca yürütülmüştür. Toplam 12 flebotomist tarafından gerçekleştirilen 300 venöz kan alma işlemi doğrudan gözlemlenmiştir. Veriler, European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) ile Clinical and Laboratory Standards Institute (CLSI) yönergelerine dayalı bir “Venöz Kan Alma Gözlem Formu” aracılığıyla toplanmıştır. Kılavuzlara uyum ve yaygın görülen hata oranları değerlendirilmiş, eğitim müdahalelerinin etkisi ikioran z testi ve ki-kare testi gibi istatistiksel yöntemler kullanılarak analiz edilmiştir. Bulgular: Numune reddinin en yaygın nedenleri “Yetersiz Numune,” “Pıhtılı Numune” ve “Hemolizli Numune” olup, tüm reddedilen numunelerin %78,69’unu oluşturmuştur. Haziran 2024’te uygulanan eğitim programının ardından, Temmuz 2024’te numune reddi oranlarında istatistiksel olarak anlamlı bir azalma gözlenmiştir (p < 0,05). Kılavuzlara uyum açısından en sık rastlanan eksiklikler arasında tüpün uygunsuz doldurulması, hatalı karıştırma ve turnikenin gereğinden uzun süre uygulanması yer almıştır. Sonuç: Bulgularımız, özellikle venöz kan alma sırasında görülen preanalitik hataların, sistematik eğitim ve standardize protokollere uyum yoluyla azaltılabileceğini göstermektedir. Hata oranlarını düşürmek, numune bütünlüğünü korumak ve hasta güvenliğini artırmak için sürekli eğitim ve kalite kontrol önlemleri kritik önem taşımaktadır. İleride yapılacak çalışmalarda, düzenli gözlemsel denetimler ve sürekliliği sağlanan personel eğitimiyle elde edilen iyileştirmelerin korunması ve yaygınlaştırılması hedeflenmelidir.