Diagnostic Biomarkers Research Articles

New frontiers in the pharmacological management of biliary tract carcinomas: the emerging role of drug conjugates.

Biliary tract cancer (BTC) is a human malignancy with a poor prognosis. However, significant progress has been made in understanding the molecular mechanisms of carcinogenesis, leading to the development of targeted therapy strategies in recent years. The challenge now is to develop new therapeutic concepts to further increase the efficacy of BTC treatments in the coming years. This review covers the emerging and advanced approaches of highly sophisticated antibody-drug conjugates (ADCs) and non-ADCs, particularly in relation to BTC. Additionally, the potential advantages and disadvantages of ADCs and non-ADCs regarding toxicities, bioavailability, and efficacy are presented and discussed. Given the poor prognosis of BTCs, new targeted and precision therapy strategies using drug conjugates - with and without antibodies as drug carriers - have the potential to overcome the limitations of conventional chemotherapy by improving treatment specificity and efficacy while reducing systemic toxicity. However, several open questions remain regarding ADCs and non-ADCs, including chemical design, drug delivery, related diagnostic and therapeutic biomarkers, and combinatory application strategies.

Diagnostic Biomarkers for Uveitis: Serum BAFF and CXCL9 in Differentiating Ocular Sarcoidosis, Tuberculosis and Other Entities with Implication for QuantiFERON-Positive Uveitis.

To evaluate serum B cell activating factor (BAFF) and CXCL9 as diagnostic biomarkers for ocular sarcoidosis and ocular tuberculosis (TB). We also explore their role in the stratification of patients with QuantiFERON (QFT)-positive uveitis without another identifiable cause. Eighty uveitis patients with various entities were included: 10 with ocular sarcoidosis, 35 with TB-related uveitis (including 11 confirmed (ocular TB) and 24 QFT-positive uveitis of unknown cause) and 35 with other uveitis entities. Levels of serum BAFF and CXCL9 were measured. Serum BAFF was higher in ocular sarcoidosis compared to other groups (area under the curve (AUC) = 0.74; 95% CI: 0.53-0.96, p = 0.017). At an optimal serum BAFF cut-off point of 772.3 pg/ml, the sensitivity was 70.0% (95% CI: 39.7-89.2) and the specificity was 89.1% (95% CI: 77.0-95.3). Serum CXCL9 was comparable between ocular sarcoidosis and confirmed ocular TB but was significantly higher in these groups compared to other uveitis entities (AUC = 0.71, 95% CI: 0.57-0.86, p = 0.011). To differentiate ocular sarcoidosis and TB from other uveitis entities, CXCL9 (cutoff: 105.5 pg/ml) showed a sensitivity of 88.9% (95% CI: 67.2-98.0) and a specificity of 54.3% (95% CI: 38.2-69.5). High CXCL9 TB-related uveitis patients demonstrated a higher proportion of uveitis resolution when fully treated with antitubercular treatment (ATT) (p = 0.027). Serum BAFF and CXCL9 serve as potential diagnostic biomarkers for differentiating ocular sarcoidosis, ocular TB and other uveitis entities. These might identify QFT-positive uveitis who are most in need of ATT.

Multiple machine learning algorithms identified SLC6A8 as a diagnostic biomarker of the late stage of Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a chronic liver disease characterized by persistent tumor growth, contributing significantly to mortality rates worldwide. Consequently, there is an urgent need to develop effective diagnostic and treatment strategies for HCC. This study aims to identify crucial genes for early HCC diagnosis to mitigate disease progression and to investigate differences in immune cell infiltration between early-stage and late-stage HCC. We integrated two published datasets for a comprehensive analysis, identifying 575 DEGs subjected to GSEA to reveal pathways distinguishing early-stage from late-stage HCC. Notably, the gene SLC6A8 emerged as a potential diagnostic biomarker for late-stage HCC through machine learning (LASSO-LR/SVM-RFE/RF-Boruta). ROC curves for SLC6A8 were utilized to evaluate diagnostic accuracy. The ImmuCellAI algorithm assessed immune cell composition differences between early and late-stage HCC, revealing that SLC6A8 expression positively correlates with resting Tfh cells and Th2, while negatively correlating with B cells, indicating its association with immune cell infiltration patterns. To strengthen our results, we further analyzed SLC6A8 expression using single-cell transcriptome data, confirming notably overexpression in late-stage HCC, particularly in key liver cell types such as Hepatocyte cells. Overall, our study nominates SLC6A8 as a dual biomarker for HCC Staging and precision therapy.

A Metabolic Signature Specific to the Patients with Type 2 Diabetes and its Association with the Pathogenesis of Diabetic-Foot Syndrome.

Oxidative stress and protein nonenzymatic glycation are key factors in diabetic-foot syndrome pathogenesis. Type 2 diabetes (T2DM) progression involves excessive gluconolactone (GDL) production, linked to endothelial injury and diabetic arteriosclerosis. This study explored GDL's role in diabetic-foot syndrome using high-performance liquid chromatography-tandem mass spectrometry to analyze sera from 75 T2DM patients (including 32 with diabetic-foot) and 36 healthy controls. GDL levels were significantly higher in T2DM patients and correlated with increased hemoglobin A1c glycation and reactive oxygen species production in endothelial cells, suggesting GDL's role in accelerating macrovascular arteriosclerosis and diabetic-foot syndrome. These findings highlight GDL's potential as a diagnostic biomarker and therapeutic target for diabetic macrovascular complications.

LncRNA CYP1B1-AS1 as a clinical biomarker exacerbates sepsis inflammatory response via targeting miR- 18a- 5p

BackgroundSepsis, characterized by high morbidity and mortality, necessitates the identification of novel diagnostic and prognostic biomarkers to enhance patient outcomes. Prior research has highlighted the potential clinical utility of long non-coding RNAs (lncRNAs) in sepsis. This study aimed to investigate the clinical significance and underlying mechanisms of serum lncRNA Cytochrome P450 family 1 subfamily B member 1 antisense RNA 1 (CYP1B1-AS1) expression in sepsis.MethodsDifferentially expressed lncRNAs in sepsis patients were explored via GEO database. Sepsis patients and Control subjects were included. An in vitro cellular model was established with LPS-stimulated THP- 1 cells. RT-qPCR assessed CYP1B1-AS1 and miR- 18a- 5p expression. ROC analysis evaluated diagnostic and predictive value. Kaplan-Meier curves and Cox regression analyzed the prognostic value of CYP1B1-AS1. Flow cytometry and ELISA assessed cell apoptosis and inflammatory factors levels. Dual luciferase reporter, RIP, and RNA pull down to validate target binding relationship.ResultsThe GSE217700 database shows that CYP1B1-AS1 was upregulated in sepsis. Serum levels of CYP1B1-AS1 were higher in sepsis patients than controls. CYP1B1-AS1 was positively correlated with SOFA and APACHE II scores and distinguished sepsis patients from controls. The 28-day mortality rate for sepsis patients was 29.31%. High CYP1B1-AS1 expression in sepsis patients predicts a worse prognosis and is a potential risk factor. CYP1B1-AS1 targets miR- 18a- 5p. Silencing CYP1B1-AS1 reduced LPS-inducted apoptosis and inflammatory factor promotion, which the miR- 18a- 5p inhibitor reversed.ConclusionCYP1B1-AS1 serves as a biomarker for sepsis diagnosis and poor prognosis, potentially promoting inflammation and apoptosis by targeting miR- 18a- 5p.

Regulation of the MAPK/ERK Pathway by miRNA-27b in Gastric Cancer: Diagnostic Implications and Therapeutic Potential of Aloin.

Globally, gastric cancer (GC) ranks as the fourth most deadly and fifth most prevalent kind of cancer. Appropriate treatment methods, precise etiology, and molecular processes of GC are still unclear. In silico and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR)-based expression of miRNA-27b was quantified in GC cell lines (AGS, MKN-28, MKN-45, NCI-N87, SNU-1), and ROC curve analysis was done to evaluate their diagnostic efficiency. In silico target prediction through miRDB and TargetScan followed by in vitro validation was done using luciferase assays. Expression analysis of MAPK/ERK target genes including GRB2, SOS1, KRAS, BRAF, MAP2K1, and MAPK1 was done using qRT-PCR and Western blot analysis, followed by ROC curve analysis to evaluate their diagnostic efficiency. GC cell lines were treated with Aloin (ALO), followed by cell viability, wound healing, and apoptosis assays. Furthermore, the expression of MAPK/ERK pathway genes in GC cell lines was evaluated by qRT-PCR following ALO treatment. The in silico analysis identified specific binding sites for miRNA-27b within the 3'UTRs of key components in the MAPK/ERK signaling pathway, including GRB2, SOS1, KRAS, BRAF, MAP2K1, and MAPK1. Luciferase reporter assays confirmed the direct interaction of miRNA-27b with these target genes, showing significantly reduced luciferase activity in cells transfected with wild-type 3'UTRs compared to controls. Expression analysis revealed that miRNA-27b was significantly downregulated in GC patients and cell lines when compared to normal controls. The downregulation of miRNA-27b was further validated through qRT-PCR in a variety of GC cell lines. ROC curve analysis demonstrated an AUC of 100 for miRNA-27b, suggesting its strong potential as a diagnostic biomarker for GC. In contrast, the expression of MAPK/ERK pathway genes was significantly upregulated in GC cell lines, with ROC analysis revealing high diagnostic accuracy for several genes, including GRB2, SOS1, and KRAS. Protein expression analysis via Western blot confirmed the upregulation of these pathway components in GC cells. Further investigation into the effects of ALO treatment showed a dose-dependent reduction in cell viability, migration, and colony formation in GC cell lines. ALO treatment also induced apoptosis, as evidenced by the upregulation of apoptotic markers and the downregulation of the anti-apoptotic molecule Bcl-2. MiRNA-27b and MAPK/ERK pathway genes (GRB2, SOS1, KRAS, BRAF, MAP2K1, and MAPK1) could serve as efficient diagnostic, prognostic, and therapeutic targets for GC patients. Furthermore, this study's findings shed light on ALO's anti-tumor capabilities by demonstrating that it inhibits GC cell migration and proliferation while restoring the expression status of MAPK/ERK pathway genes.

Bioinformatics analysis of oxidative phosphorylation-related differentially expressed genes in osteoporosis

BackgroundOsteoporosis (OP) is a common metabolic bone disease characterized by decreased bone mass and increased fracture risk. Recent studies suggest that oxidative phosphorylation (OXPHOS) plays a crucial role in the pathogenesis of OP. This study aims to investigate the differential expression and potential functional roles of OXPHOS-related genes in OP.MethodsWe downloaded gene expression data from two OP-related datasets, GSE56815 and GSE7429, using the GEOquery package. We also collected OXPHOS-related genes from the GeneCards and MsigDB databases. The limma package was used for differential expression analysis of GSE56815, and differentially expressed genes (DEGs) were identified. We intersected these DEGs with OXPHOS-related genes to identify OXPHOS-related differentially expressed genes. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), were conducted using the clusterProfiler package. Additionally, we performed gene set enrichment analysis (GSEA). The Mann–Whitney U test analyzed differences in the expression of OXPHOSRDEGs, and their diagnostic potential was assessed by Receiver Operating Characteristic (ROC) curves. Correlation analysis, Protein–Protein Interaction (PPI) network construction, mRNA-miRNA, mRNA-TF interaction network construction, and immune infiltration analysis using CIBERSORT were also conducted. RAW264.7 cells were induced in vitro for 3 days to differentiate towards osteoblasts, and RT-PCR assay was used to verify the differentiation and detect the differential expression of target genes.ResultsOur results identified 31 DEGs in GSE56815, with 26 upregulated and 5 downregulated genes. Among these, we identified 10 OXPHOSRDEGs: VPS35, TBC1D2, UBQLN2, SH3GLB2, WWP1, NFKBIA, MFSD10, SLC2 A3, RP2, and ZNF91. GO and KEGG enrichment analyses revealed significant involvement of these genes in mechanisms such as the positive regulation of the protein catabolic process and the endocytosis pathway. ROC analysis demonstrated high diagnostic accuracy for VPS35 (AUC = 0.832) and TBC1D2 (AUC = 0.751). Correlation analysis indicated strong relationships between certain OXPHOSRDEGs. The PPI network highlighted 8 hub genes with significant functional similarity among them.ConclusionThis study systematically elucidates the differential expression and potential mechanisms of OXPHOS-related genes in OP through comprehensive bioinformatics analyses. The identified key genes offer valuable insights into the molecular underpinnings of OP and present potential diagnostic biomarkers and therapeutic targets for further investigation.

Screening colorectal cancer associated autoantigens through multi-omics analysis and diagnostic performance evaluation of corresponding autoantibodies

BackgroundThis study aims to screen, validate novel biomarkers and develop a user-friendly online tool for the detection of colorectal cancer (CRC).MethodsMulti-omics approach, comprising proteomic analysis and single-cell transcriptomic analysis, was utilized to discover candidate tumor-associated antigens (TAAs). The presence of tumor-associated autoantibodies (TAAbs) in serum was subsequently assessed using enzyme-linked immunosorbent assays (ELISA) in 300 CRC patients and 300 healthy controls. Ten machine learning algorithms were utilized to develop diagnostic models, with the optimal one selected and integrated into an R Shiny-based GUI to enhance usability and accessibility.ResultsWe identified twelve potential TAAs: HMGA1, NPM1, EIF1AX, CKS1B, HSP90AB1, ACTG1, S100A11, maspin, ANXA3, eEF2, P4HB, and HKDC1. ELISA results showed that five TAAbs including anti-CKS1B, anti-S100A11, anti-maspin, anti-ANXA3, and anti-eEF2 were potential diagnostic biomarkers during the diagnostic evaluation phase (all P < 0.05). The Random Forest model yielded an AUC of 0.82 (95% CI: 0.78–0.88) on the training set and 0.75 (95% CI: 0.68–0.82) on the test set, demonstrating the robustness of the results. Web-based implementations of CRC diagnostic tools are publicly accessible via weblink https://qzan.shinyapps.io/CRCPred/.ConclusionsA five biomarker panel can server as complementary biomarker to CEA and CA19-9 in CRC detection.

Identification of serum C4BPA as a potential diagnostic marker of right ventricular remodelling via proteomic analysis.

Right ventricular (RV) remodelling, a progressive condition characterized by maladaptive cardiac structural and functional changes, primarily results from prolonged pressure overload in patients with pulmonary hypertension (PH). Accurate, universal and easy-to-use biomarkers for assessing the severity of RV remodelling are lacking. This study aimed to identify serum proteins as potential biomarkers of RV remodelling using high-throughput proteomic analysis-based screening. Sprague-Dawley rats were subjected to sham surgery (control group) or pulmonary artery banding for 4weeks with 2.3-mm diameter and 1.8-mm diameter rubber rings to induce mild and severe RV modelling, respectively. Serum proteomic profiling revealed 170 differentially expressed serum proteins (DEPs) among the three groups, and three DEPs gradually increased with worsening RV remodelling. Among the three DEPs, C4b-binding protein alpha chain (C4BPA) exhibited the highest upregulation in the severe group (6.93 vs. 16.5ng/mL, P<0.001), and linear regression analysis revealed a negative correlation between serum C4BPA levels and tricuspid annular plane systolic excursion (TAPSE) in rats [beta=-0.78, 95% confidence interval (CI) -14.5 to -7.11, P<0.001]. The diagnostic power of C4BPA was further validated in 127 patients (34 with adaptive RV pressure overload, 36 with maladaptive RV pressure overload, 32 with left ventricular hypertrophy and 25 controls). Control and left ventricular hypertrophy patients exhibited lower serum C4BPA levels than the two RV groups, and serum C4BPA levels were higher in patients with maladaptive RV than in those with adaptive RV (754 vs. 524pg/mL, P<0.001). Linear regression analysis revealed a negative correlation between serum C4BPA levels and TAPSE in PH patients. The predictive power of C4BPA for maladaptive RV function in PH patients, indicated by receiver operating characteristic analysis (cut-off value 573pg/mL, area under the curve 0.792), was as good as that of B-type natriuretic peptide (BNP). High serum C4BPA levels (≥573pg/mL) were associated with lower TAPSE/pulmonary arterial systolic pressure ratios (P<0.001) and higher BNP levels (P<0.001). Serum C4BPA may represent a novel diagnostic biomarker for RV pathological remodelling associated with RV maladaptation in PH patients.

Exploring the molecular mechanisms of subarachnoid hemorrhage and potential therapeutic targets: insights from bioinformatics and drug prediction

Subarachnoid hemorrhage (SAH) is a fatal pathological condition in the central nervous system (CNS), characterized by severe clinical consequences. Its treatment remains a significant challenge, especially due to the incomplete understanding of its molecular mechanisms. In this study, we integrated comprehensive bioinformatics analyses with experimental validation to explore the potential pathogenic mechanisms and immune cell infiltration characteristics of SAH, aiming to identify novel diagnostic biomarkers and therapeutic targets. We selected relevant gene expression data from the gene expression omnibus (GEO) database and obtained a gene set associated with SAH from the GeneCards database. Through bioinformatics analysis, we constructed a protein-protein interaction (PPI) network and performed functional enrichment analysis using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases. The analysis revealed 11 key genes and indicated 3 main signaling pathways. Additionally, Drug target prediction and molecular docking analyses revealed that Isorhynchophylline (IRN) exhibits a strong binding affinity to these hub proteins. Importantly, Western blot (WB) experiments confirmed that IRN significantly downregulates the expression of CCL20, IL6, TLR4, and MMP9 in LPS-induced microglial cells, validating its anti-inflammatory effects. In conclusion, our findings not only elucidate the molecular mechanisms underlying SAH but also provide robust bioinformatics and experimental evidence supporting IRN as a promising therapeutic candidate, offering novel insights for future intervention strategies in SAH.

Exosomal Biomarkers: A Comprehensive Overview of Diagnostic and Prognostic Applications in Malignant and Non-Malignant Disorders

Exosomes are small extracellular vesicles, ranging from 30 to 150 nm, that are essential in cell biology, mediating intercellular communication and serving as biomarkers due to their origin from cells. Exosomes as biomarkers for diagnosing various illnesses have gained significant investigation due to the high cost and invasive nature of current diagnostic procedures. Exosomes have a clear advantage in the diagnosis of diseases because they include certain signals that are indicative of the genetic and proteomic profile of the ailment. This feature gives them the potential to be useful liquid biopsies for real-time, noninvasive monitoring, enabling early cancer identification for the creation of individualized treatment plans. According to our analysis, the trend toward utilizing exosomes as diagnostic and prognostic tools has raised since 2012. In this regard, the proportion of malignant indications is higher compared with non-malignant ones. To be precise, exosomes have been used the most in gastrointestinal, thoracic, and urogenital cancers, along with cardiovascular, diabetic, breathing, infectious, and brain disorders. To the best of our knowledge, this is the first research to examine all registered clinical trials that look at exosomes as a diagnostic and prognostic biomarker.

Serum fibrinogen is not elevated in patients with myasthenia gravis

Myasthenia gravis (MG) is an autoimmune, autoantibody-mediated disease characterized by fatigable weakness of skeletal muscles. MG is a heterogeneous disease that currently lacks a robust biomarker for diagnosing all subtypes. Residual serum fibrinogen was found to be elevated 1000-fold in patients with MG in one study and posited to represent a universal diagnostic biomarker for MG. We set out to confirm elevated serum fibrinogen in patients with all subtypes of MG. We employed multiple methodologies to compare fibrinogen levels between MG patients and controls, using samples from independent cohorts. With enzyme-linked immunosorbent assay (ELISA), fibrinogen levels in sera from MG patients were not significantly different from controls. And in plasma samples, MG patients had a significantly lower amount of fibrinogen compared to controls. Using liquid chromatography-mass spectrometry (LC-MS), the abundance of serum fibrinogen-α was not elevated in patients compared to controls, and patients had a significantly lower abundance of serum fibrinogen-ß and fibrinogen-γ compared to controls. Our results do not support serum fibrinogen to be a diagnostic biomarker for MG and underscore the need for replication of novel findings to ensure our common goal of identifying effective biomarkers for MG.

Exosomal biomarkers: A novel frontier in the diagnosis of gastrointestinal cancers.

Gastrointestinal (GI) cancers, which predominantly manifest in the stomach, colorectum, liver, esophagus, and pancreas, accounting for approximately 35% of global cancer-related mortality. The advent of liquid biopsy has introduced a pivotal diagnostic modality for the early identification of premalignant GI lesions and incipient cancers. This non-invasive technique not only facilitates prompt therapeutic intervention, but also serves as a critical adjunct in prognosticating the likelihood of tumor recurrence. The wealth of circulating exosomes present in body fluids is often enriched with proteins, lipids, microRNAs, and other RNAs derived from tumor cells. These specific cargo components are reflective of processes involved in GI tumorigenesis, tumor progression, and response to treatment. As such, they represent a group of promising biomarkers for aiding in the diagnosis of GI cancer. In this review, we delivered an exhaustive overview of the composition of exosomes and the pathways for cargo sorting within these vesicles. We laid out some of the clinical evidence that supported the utilization of exosomes as diagnostic biomarkers for GI cancers and discussed their potential for clinical application. Furthermore, we addressed the challenges encountered when harnessing exosomes as diagnostic and predictive instruments in the realm of GI cancers.

3-Fucosyllactose Prevents Nonalcoholic Fatty Liver Disease by Modulating the Gut Microbiota-Derived Pantothenate in Mice.

Nonalcoholic fatty liver disease (NAFLD) is a growing global health threat. Human milk oligosaccharides (HMOs) exhibit prebiotic properties that may alleviate NAFLD progression. Herein, our study demonstrates that 3-fucosyllactose (3-FL), a distinctive and crucial HMO, significantly attenuates body weight gain, enhances hepatic lipid metabolism, and reduces inflammation in a high-fat diet (HFD)-induced NAFLD mouse model. These findings suggest its potential as a dietary supplement for preventing and alleviating NAFLD progression. Subsequently, fecal metagenomic and nontargeted metabolomics analyses revealed that 3-FL treatment significantly alleviated HFD-induced gut microbiota dysbiosis, with a specific enhancement of the pantothenate (vitamin B5) metabolic pathways. Our targeted metabolite analysis further revealed a significant increase in both hepatic and fecal pantothenate concentrations, which contributed to the enhancement of the coenzyme A (CoA)-mediated lipid metabolism pathway. Furthermore, the subsequent population cohort analyses revealed a significant correlation between serum pantothenate levels and the progression of NAFLD, thereby reinforcing its candidacy as a noninvasive diagnostic biomarker. These findings show that 3-FL acts as an effective prebiotic to alleviate NAFLD symptoms, in part by enhancing the gut microbiota-mediated pantothenate/CoA metabolic pathway.

The Clinical Diagnostic Value of Serum Exosomal Proteins PAPP-A and CAMK2β in Gestational Diabetes Mellitus

Abstract This study evaluates the potential of exosomal proteins pregnancy-associated plasma protein-A (PAPP-A) and calcium/calmodulin-dependent protein kinase 2β (CAMK2β) as early diagnostic biomarkers for gestational diabetes mellitus (GDM) and investigates their roles and associated signaling pathways in GDM. Serum exosomes from serum were analyzed for protein levels of PAPP-A and CAMK2β, correlating with metabolic indicators and pregnancy outcomes. Diagnostic accuracy was assessed using ROC curves, with AUC values of 0.843 for PAPP-A and 0.895 for CAMK2β, indicating high diagnostic potential. Despite distinct expression patterns in GDM patients compared to healthy pregnant women with PAPP-A linked to early pregnancy BMI and lipid levels, while CAMK2β showed an inverse trend, neither protein significantly correlated with delivery outcomes, suggesting the need for further exploration into their roles in GDM pathogenesis bioinformatics analysis revealed that PAPP-A is involved in insulin-like growth factors (IGFs), growth factor (GFs) signaling, glucose metabolic processes, and the MAPK pathway, while CAMK2β is associated with intracellular calcium signaling and ion transport. These findings highlight the multifaceted regulatory roles of PAPP-A and CAMK2β in metabolic diseases and biological processes relevant to GDM. Our results position these serum exosomal proteins as promising early GDM biomarkers, offering new insights for clinical diagnosis and potentially guiding prevention and treatment strategies.

LncRNA PAN3-AS1 Modulates Cilium Assemble Signaling Pathway Through Regulation of RPGR as a Potential MS Diagnostic Biomarker: Integrated Systems Biology Investigation.

Multiple sclerosis (MS), an autoimmune condition of the central nervous system (CNS), can lead to demyelination and axonal degeneration in the brain and spinal cord, which can cause progressive neurologic disability. MS symptoms include dysautonomia and progressive decline in motor abilities. In this investigation, we performed an integrated bioinformatics and experimental approach to find the expression level and interaction of a novel long non-coding RNA (lncRNA), PAN3-AS1, in MS samples. Microarray analysis was performed by R Studio using GEOquery and limma packages. lncRNA-mRNA RNA interaction analysis was performed using the lncRRIsearch database. Pathway enrichment analysis was performed by KEGG and Reactome online software through the Enrichr database. Protein-protein interaction analysis was performed by STRING online software. Gene ontology (GO) analysis was performed by Enrichr database. Based on microarray analysis, lncRNA PAN3-AS1 has a significantly low expression in MS samples compared to the control (logFC - 1.2, adj. P. Val 0.03). qRT-PCR results approved bioinformatics analyses. ROC analysis revealed that PAN3-AS1 could be considered a potential diagnostic biomarker of MS. Based on lncRNA-mRNA interaction analysis, lncRNA PAN3-AS1 regulates the expression level of RPGR. RPGR and its protein interactome regulate the cilium assembly, chaperon-mediated autophagy, and microarray biogenesis. lncRNA PAN3-AS1, as a significant low-expressed lncRNA in MS samples, could be a potential diagnostic MS biomarker. PAN3-AS1 might regulate the expression level of cilium assembly and chaperon-mediated autophagy. Dysregulation of PAN3-AS1 might affect the expression of RPGR and its protein interactome.

The role of IL-6 in thyroid eye disease: an update on emerging treatments

Elevated serum interleukin-6 (IL-6) levels have been shown to correlate with disease activity in patients with thyroid eye disease (TED), a complex, heterogeneous, autoimmune disease affecting thousands of people worldwide. IL-6 plays a pivotal role in the pathogenesis of TED through three key mechanisms that together may contribute to inflammation, tissue expansion, remodeling, and fibrosis within the orbit. First, IL-6 drives an autoimmune response targeting the thyroid-stimulating hormone receptor (TSHR) by promoting the production of autoantibodies (i.e. TSHR-Ab, TSI), thereby triggering TSHR-dependent immune pathways. Second, IL-6 stimulates the activation and differentiation of orbital fibroblasts, which contributes to the inflammatory process and increase adipogenesis. Finally, IL-6 stimulates T-cell–mediated inflammation, amplifying the immune response within orbital tissues. Although corticosteroids and surgery have served as mainstays of TED treatment, a multimodal approach is often required due to the disease’s heterogeneous presentation and response to current treatment options. TED is a chronic, lifelong condition characterized by periods of exacerbation and remission, with inflammation playing a central role in disease progression and severity. Because inflammation can flare intermittently throughout a patient’s life, there is growing interest in targeting specific components of the immune system to reduce disease activity and severity. This review focuses on the current evidence supporting IL-6 as a key mediator of TED pathogenesis and explores its potential as a diagnostic biomarker and therapeutic target of the disease.

Exploring the molecular pathways of miRNAs in testicular cancer: from diagnosis to therapeutic innovations.

Cancer diagnostics highlight the critical requirement for sensitive and accurate tools with functional biomarkers for early tumor detection, diagnosis, and treatment. With a high burden of morbidity and mortality among young men worldwide and an increasing prevalence, Testicular cancer (TC) is a significant death-related cancer. Along with patient history, imaging, clinical presentation, and laboratory data, histological analysis of the testicular tissue following orchiectomy is crucial. Although some patients in advanced stages who belong to a poor risk group die from cancer, surgical treatments and chemotherapeutic treatment offer a high possibility of cure in the early stages. Testicular tumors lack useful indicators despite their traditional pathological classification, which highlights the need to find and use blood tumor markers in therapy. Regretfully, the sensitivity and specificity of the currently available biomarkers are restricted. Novel non-coding RNA molecules, microRNAs (miRNAs), have recently been discovered, offering a potential breakthrough as viable biomarkers and diagnostic tools. They act as fundamental gene regulators at the post-transcriptional level, controlling cell proliferation, differentiation, and apoptosis. This article aims to comprehensively explore the role of miRNAs in the pathophysiology, diagnosis, and treatment of TC, with a focus on their regulatory mechanisms within key signaling pathways such as TGF-β, PTEN/AKT/mTOR, EGFR, JAK/STAT, and WNT/β-catenin. By investigating the potential of miRNAs as diagnostic and prognostic biomarkers and therapeutic targets, this study seeks to address challenges such as treatment resistance and evaluate the clinical importance of miRNAs in improving patient outcomes. Additionally, the work aims to explore innovative approaches, including nanoparticle-based delivery systems, to enhance the efficacy of miRNA-based therapies. Ultimately, this research aims to provide insights into future directions for precision medicine in TC, bridging the gap between molecular discoveries and clinical applications.

A Large-Scale Retrospective Study of Serum Des-Gamma-Carboxy Prothrombin as a Diagnostic Marker of HCC: Effect of Liver Function on Specificity.

This retrospective multicenter study is aimed at evaluating the diagnostic accuracy and influence factors of serum des-gamma-carboxy prothrombin (DCP) as a diagnostic biomarker of hepatocellular carcinoma (HCC). Clinical data were collected from 4555 subjects with DCP tests, composed of primary liver cancer (PLC), metastatic liver cancer (MLC), chronic hepatitis (CH), liver cirrhosis (LC), benign liver diseases (BLD), biliary tract diseases (BTD), non-liver cancers (NLC), and non-liver benign diseases (NLBD). The clinical data collected included medical history, treatment records, various serum tests, and imaging examination. Serum DCP was measured with Abbott agents in each center. In HCC, serum DCP concentration was at 9086.00 ± 366.10 mAU/mL, higher than that in other diseases (p < 0.05). At 40.00 mAU/mL recommended by instruction, positive rates of serum DCP were at 85.11% in HCC, 30.12% in intrahepatic cholangiocellular carcinoma (ICC), 31.65% in MLC, 13.95% in BLD, 18.14% in CH, 27.87% in LC, 15.75% in BTD, 35.29% in NLC, and 20.00% in NLBD. In this study, the diagnostic specificity of serum DCP in HCC was affected by liver function. In HCC, serum AFP concentrations also increased compared to non-HCC diseases (p < 0.05), but specificity varied with agents from different providers. Serum DCP decreased after the surgical removal of HCC, but remained elusive in systemic treatment. Serum DCP may serve as an optimal biomarker for the diagnosis of HCC, but its accuracy appears influenced by liver function; attention needs to be paid to the liver function of patients for false positivity.

Associations of serum MANF with severity and prognosis in community-acquired pneumonia patients

Mesencephalic astrocyte-derived neurotrophic factor (MANF), a novel endoplasmic reticulum stress-induced neurotrophic factor, exerts a protective role in both nervous and non-nervous systems. However, the relationship between serum MANF content and community-acquired pneumonia (CAP) patients remains unclear. A total of 319 adult patients diagnosed with CAP were enrolled. Serum MANF level was quantified using enzyme-linked immunosorbent assay (ELISA). A prospective cohort study was conducted to investigate the association of serum MANF levels with severity and prognosis. Compared with healthy volunteers, serum MANF content was evidently upregulated in CAP patients. The level of serum MANF was dramatically increased in parallel with the scores of CURB-65, PSI, APACHE II, and SMART-COP in CAP cases. Additionally, multivariate linear and logistic regression analyses revealed that serum MANF level was positively associated with scoring criteria among CAP patients. Besides, serum MANF level on admission was significantly elevated in CAP patients who required mechanical ventilation, ICU admission, and died within 30 days. Moreover, the higher serum MANF level on admission evidently increased the risk of poor prognosis during hospitalization. There was a better predictive power of serum MANF for poorly prognostic outcomes in CAP patients. The expression of serum MANF exhibits the positive correlations with the severity and poor prognosis among CAP patients. Serum MANF may have considerable clinical value and be regarded as a diagnostic and prognostic biomarker for CAP.