Search Results (2,923)

Myopathies represent a highly heterogeneous group of primary muscle disorders, traditionally classified based on clinical presentation and histopathological findings. Recent breakthroughs in molecular genetics, immunology, and pathophysiology have revolutionized the understanding, diagnosis, and management of these conditions. Both inherited and acquired forms of myopathy, including structural, metabolic, inflammatory, endocrine, and mitochondrial subtypes, are now recognized to arise from diverse pathogenic mechanisms such as impaired calcium handling, mitochondrial dysfunction, chronic inflammation, altered metabolism, and defective muscle regeneration. The advent of next-generation sequencing technologies has enabled more precise diagnosis of genetic forms, while the discovery of novel molecular biomarkers and immunological signatures offers promising avenues for disease monitoring and stratification across the broader spectrum. Importantly, molecular and mechanistic insights have redefined clinical classifications, allowing for better prognostic predictions and patient-tailored therapeutic approaches. Innovative treatments, including gene therapy, antisense oligonucleotide therapies, immune-modulating agents, metabolic support strategies, and targeted pharmacological interventions, are progressively translating molecular knowledge into clinical applications. However, technical limitations, biological variability, and ethical considerations continue to pose significant challenges to the implementation of precision medicine in myopathies. In this narrative review, we comprehensively discuss the latest molecular findings, their integration into clinical practice, and the emerging therapeutic strategies based on these discoveries. We also highlight current limitations and propose future research directions aimed at bridging the gap between molecular insights and effective, equitable patient care. Full article

Transposable elements (TEs) are key regulators of immunity in both health and disease. It has been proven that the activity and transcriptional expression levels of TEs increase during viral infections, correlating with the antiviral response. This study investigates non-LTR TE (LINE, SINE, and SVA) transcriptomic signatures in human PBMCs during infections caused by influenza A virus, HIV, and SARS-CoV-2 (Delta/Omicron variants) using single-cell RNA sequencing (scRNA-seq) data from 98 patients. In the HIV and SARS-CoV-2 patient cohorts, unique cell-specific TE expression patterns were identified that allow for the differentiation of disease severity, prediction of disease progression, and assessment of the therapy’s efficacy. The expression of LINE elements was found to be more dependent on the nature and course of the disease than that of SINE elements. The most variable TE expression profile was observed in precursor cytotoxic T-lymphocytes (T CD8+ Naive cells), which depended on the virus type and the severity of the viral disease. For this cell type, a bioinformatic analysis of the co-expression regulation of TE transcriptional networks and transcription factors during viral infections was performed. This analysis identified key players among those most involved in virus-specific responses, which could serve as diagnostic biomarkers or therapeutic targets for treating diseases caused by influenza A virus, HIV, and SARS-CoV-2. This work confirms the involvement of non-LTR TEs in mediating antiviral responses. Further research into the mechanisms of TE participation in antiviral defense is necessary to recommend them as potential biomarkers for the diagnosis, monitoring, and assessment of antiviral therapy, or as therapeutic targets for viral infections of various origins. Full article

IgA nephropathy (IgAN) is the most common primary chronic glomerular disease worldwide. Its clinical features include proteinuria and complement pathway activation, which are the strongest predictors of progression to renal failure. This disease can occur at any age. Approximately 30–40% of IgAN patients progress to end-stage renal disease (ESRD) within 20–25 years after diagnosis, making it one of the major causes of ESRD. As understanding of the autoimmune development of IgA nephropathy (IgAN) grows, research shows that BAFF and APRIL promote B-cell activation by binding to the receptors TACI, BCMA, and BAFF-R. This results in the overproduction of galactose-deficient IgA1 (Gd-IgA1), which helps drive the progression of IgA nephropathy. B-cell and plasma cell-targeted therapies, such as biologics against BAFF/APRIL, can precisely and effectively improve patient symptoms. Corresponding agents have now been successfully developed and are administered via subcutaneous or intravenous injection. Clinical trials have demonstrated the significant effectiveness of this approach, especially in reducing proteinuria, stabilizing eGFR, and lowering Gd-IgA1 levels. Although current trial data for BAFF/APRIL-targeted biologics in IgA nephropathy are promising, these new treatments need ongoing clinical monitoring for long-term infection risks and potential drug resistance. This article focuses on the application of BAFF/APRIL biologics in the treatment of IgA nephropathy, addressing gaps in existing literature. While prior studies have emphasized the mechanisms of action of these drugs in IgA nephropathy, they have lacked a comprehensive summary of the current status of specific drug research and clinical progress. Full article

Immune checkpoint inhibitors are essential treatments for many oncologic diseases, but with well-known immune-related adverse events, such as acute interstitial nephritis (ICI-AIN). We investigated novel potential biomarkers that could assist in the diagnosis and follow-up of this condition and that are related to the active pathogenic pathways involved. We measured urinary soluble PD-1, PD-L1 and PD-L2, as well as chemokines CXCL5, CXCL9, CXCL10, CXCL11, CCL2, CCL3, CCL5 and cytokines IL-6 and IL-12p70 performing a Luminex assay in urine from patients with ICI-AIN (n = 35) and compared them with patients with AIN from other causes (non-ICI AIN) (n = 29) and ATN (n = 26). We found that CXCL5, CXCL9, CXCL10, CXCL11, CCL5 and IL-6 were higher in patients with ICI-AIN than in those with ATN, and all of them but CXCL9 and IL-6 were also higher in patients with ICI-AIN compared with non-ICI AIN. We also determined these molecules at follow-up for ICI-AIN patients (40 samples from 22 patients) and found that concentrations of CXCL9, CXCL10, CXCL11 and CCL2 decreased after treatment. The decrease of CXCL9 and CXCL10 correlated with greater kidney function recovery at one-year follow-up. These molecules could serve as noninvasive biomarkers and may aid fine patient monitoring. Full article

The clinical management of myeloid neoplasms increasingly relies on the accurate detection and longitudinal monitoring of disease-defining genetic alterations. Many clinically relevant mutations are often present at very low variant allele frequencies, below the detection limits of conventional approaches routinely used in diagnostic workflows. In recent years, a growing number of ultra-sensitive molecular technologies have been developed to overcome these limitations, enabling the detection of rare variants with unprecedented precision, offering complementary strengths in terms of sensitivity, quantification, throughput, and clinical applicability. This review provides a comprehensive overview of established and emerging ultra-sensitive technologies for the diagnosis and molecular monitoring of myeloid neoplasms, discussing their technical principles, advantages, and limitations. Full article

Ocular melanomas, comprising uveal melanoma (UM) and conjunctival melanoma (CoM), represent the most common primary intraocular and ocular surface malignancies in adults. Although rare compared with cutaneous melanoma, they exhibit unique molecular landscapes that provide critical opportunities for biomarker-driven precision medicine. In UM, recurrent mutations in GNAQ and GNA11, together with alterations in BAP1, SF3B1, and EIF1AX, have emerged as key prognostic biomarkers that stratify metastatic risk and guide surveillance strategies. Conversely, in CoM, the mutational spectrum overlaps with cutaneous melanoma, with frequent alterations in BRAF, NRAS, NF1, and KIT, offering actionable targets for personalised treatment. Beyond genomics, epigenetic signatures, microRNAs, and protein-based markers provide further insights into tumour progression, microenvironmental remodelling, and immune evasion. In parallel, liquid biopsy has emerged as a minimally invasive approach for real-time disease monitoring. Analyses of circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and exosome-derived microRNAs demonstrate increasing potential for early detection of minimal residual disease, prognostic assessment, and evaluation of treatment response. However, the clinical integration of these biomarkers remains limited by tumour heterogeneity, technical variability, and the lack of unified translational frameworks. This review synthesises current knowledge of molecular and liquid biopsy biomarkers in ocular melanoma, highlighting their relevance for diagnosis, prognosis, and treatment personalisation. The integration of established tissue-based molecular markers with novel liquid biopsy technologies will enable a unique framework for biomarker-guided precision oncology and risk-adapted surveillance in uveal and conjunctival melanoma, offering insight into strategies for early detection, therapeutic monitoring, and personalised clinical management. Full article

Background/Objectives: Differential diagnosis between Crohn’s disease (CD) and ulcerative colitis (UC) can be sometimes difficult resulting in the diagnosis of unspecified inflammatory bowel diseases (IBD-U). Data suggest that IgG antibodies against integrin αvβ6 (V6 Ab) help to identify UC patients. Recent studies suggest that measuring V6 Ab serum levels may be valuable for differential diagnostic purposes. The primary objective of the study was to assess the sensitivity and specificity of V6 Ab serum-level measurement in our IBD population to differentiate between colonic/ileocolonic CD and UC with an established diagnosis. Furthermore, we assessed the correlation between disease characteristics, activity and V6 Ab serum levels in UC patients. Methods: Consecutive IBD patients with an established diagnosis undergoing control colonoscopy in a tertiary IBD center were included. Baseline demographic data, current treatment, disease extent, clinical, biomarker, endoscopic and histologic disease activity were collected. V6 Ab serum levels were measured with the Anti-Integrin αvβ6 ELISA Kit (RUO). Patients’ written informed consent was obtained. Results: A total of 40 IBD patients, including 10 CD and 30 UC patients (15 with clinical activity and 15 in clinical remission) were enrolled. V6 Ab serum levels were significantly higher in UC patients compared to CD (p = 0.039). ROC analysis found 1.33 U/mL to be the best cut-off level (p = 0.04; AUC: 0.71) with 100% sensitivity and 50% specificity and a positive predictive value of 85.7% and a negative predictive value of 100% to differentiate between UC and CD. No significant correlation was found between V6 Ab serum levels and CRP (p = 0.057), fecal calprotectin (p = 0.77), endoscopic activity (p = 0.624) or disease extent (p = 0.624) in UC patients. Conclusions: Our study supports the value of V6 Ab serum level measurement as a differential diagnostic tool in IBD patients; however, the optimal cut-off value is yet to be determined. Our data do not support its role in disease activity monitoring. Full article

Early and accurate diagnosis is critical for disease surveillance, therapeutic guidance, and relapse monitoring. Sensor arrays have emerged as a multi-analyte detection tool via non-specific interactions to generate unique fingerprint patterns with high levels of selectivity and discrimination. Conjugated polymers (CPs), with their tunable π-conjugated backbones, exceptional light-harvesting capability, and efficient “molecular wire effect,” provide an ideal and versatile material platform for such arrays, enabling significant optical signal amplification and high sensitivity. This review systematically outlines the rational design and functionalization strategies of CPs for constructing high-performance sensor arrays. It delves into the structure–property relationships that govern their sensing performance, covering main-chain engineering, side-chain functionalization, and microenvironmental regulation. Representative applications are discussed, including non-small cell lung cancer, breast cancer, bacterial and viral infections, Alzheimer’s disease, and diabetic nephropathy, highlighting the remarkable diagnostic capabilities achieved through tailored CP materials. Finally, future perspectives are focused on novel material designs and device integration to advance this vibrant field. Full article

Pathological reduction in enzymatic activity of the tissue-non-specific alkaline phosphatase (TNSALP) is the molecular hallmark of hypophosphatasia (HPP), a group of rare inborn systemic diseases, mainly characterized by pathological affections of calcified tissue mineralization and the musculoskeletal system. The disease, in all clinical forms, is biochemically characterized by variable degrees of chronically reduced activity of circulating total alkaline phosphatase (ALP). Repeated detection of low values of ALP activity is mandatory to diagnose the presence of HPP, but, alone, it is not sufficient for the diagnosis of the disease. Detection of increased circulating levels of one of the main natural substrates of TNSALP, the pyridoxal 5′-phosphate (PLP), is needed to biochemically confirm the diagnosis of HPP. Urinary and/or blood levels of phosphoethanolamine (PEA) and inorganic pyrophosphate (PPi), two other natural substrates of TNSALP, can be elevated in a percentage of HPP patients. The contemporary biochemical evaluation of ALP activity and its target substrates is of great help in the diagnosis of HPP, and also for the monitoring of a patient’s response to enzymatic replacement therapy or other pharmacological treatments. Here, we describe and discuss possibilities and challenges of biochemical screenings for HPP, based also on the experience gained in our analysis laboratory. Full article

Perianal fistulizing Crohn’s disease (pfCD) represents one of the most challenging manifestations of CD, often associated with severe phenotypes, refractory luminal inflammation, and a substantial reduction in quality of life. Its pathogenesis is multifactorial and incompletely understood, involving genetic susceptibility, epithelial and stromal dysfunction, and microbiome-related mechanisms. Diagnosis and monitoring rely on advanced imaging, while management requires coordinated medical–surgical strategies. Significant unmet needs persist regarding standardized treatment targets, optimal imaging follow-up, and personalized therapeutic pathways. In this review, we aim to summarise and provide a comprehensive overview of the most recent evidence across pathogenesis, diagnosis, classification systems, and therapeutic approaches in pfCD. We highlight key advances in understanding epithelial–mesenchymal transition, immune–microbiome interactions, and genetic determinants of disease behaviour. Improvements in diagnostic modalities—including MRI-based scores, ultrasound technologies, volumetric assessment, and AI-enhanced imaging—are discussed alongside modern classification systems such as TOPClass. Evidence guiding medical therapy, seton management, and surgical decision-making is reviewed, emphasising integrated, goal-oriented care. Despite substantial progress, pfCD remains a difficult-to-treat condition with persistent gaps in early diagnosis, objective monitoring, and individualized management. Emerging imaging technologies, standardized treatment targets, and structured classification frameworks offer promising strategies to overcome current limitations and improve long-term outcomes. Full article

The biomarker landscape in rheumatoid arthritis (RA) is evolving from reliance on traditional markers toward integrated, multimodal strategies enabling precision medicine approaches. To critically evaluate emerging biomarkers across serological, cellular, genetic, imaging, and multi-omic domains, distinguishing those approaching clinical readiness from those requiring further development. In this study, a narrative review of the literature published between 2000 and 2024 relevant to clinical decision-making in RA was conducted. Among novel serological markers, 14-3-3η protein and anti-carbamylated protein antibodies show the strongest validation for seronegative disease and prognostic stratification. Calprotectin demonstrates utility for disease activity monitoring and de-escalation decisions. Multi-biomarker disease activity scores provide an objective assessment but lack outcome trial validation. Musculoskeletal ultrasound offers accessible imaging biomarker capability, while MRI bone marrow edema remains the strongest structural progression predictor. Synovial tissue pathotyping has demonstrated proof-of-concept for treatment stratification. Genetic, epigenetic, and metabolomic approaches remain investigational. Key clinical implications include using 14-3-3η and calprotectin to inform seronegative diagnosis and de-escalation decisions, integrating ultrasound for remission verification, and recognizing that emerging biomarkers for extra-articular complications, including cardiovascular risk and venous thromboembolism, represent important unmet needs. Full article

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer subtype and, in most cases, it is incidentally diagnosed, as early-stage disease is often asymptomatic. Therefore, the identification of stable, noninvasive biomarkers is a major unmet clinical need. Urinary microRNAs (miRNAs) have emerged as promising candidates since they are extraordinarily stable in urine and show a close relationship with tumour biology. Methods: In this study, urinary expression levels of five miRNAs (miR-15a, miR-15b, miR-16, miR-210, and miR-let-7b) were analysed in RCC patients before surgery, 5 days after, and one month after surgery, and compared to healthy controls. Results: Non-parametric analyses revealed significant postoperative decreases for miR-15a (p = 0.002), miR-16 (p = 0.025), miR-210 (p = 0.030), and in the overall miRNA Sum (p = 0.002), suggesting that these miRNAs are directly linked to tumour presence. In the comparison between preoperative and one-month postoperative samples, miR-let-7b (p = 0.049) and the global miRNA Sum (p = 0.037) remained significantly reduced after intervention, indicating a partial normalisation of urinary miRNA profiles. Correlation analyses demonstrated positive associations between specific miRNAs and clinical parameters such as age, ischemia time, and surgical time, reinforcing their potential relevance to tumour biology and treatment response. Conclusions: These findings support urinary miRNAs as promising, minimally invasive biomarkers for ccRCC diagnosis and postoperative monitoring. Full article

Endometriosis is traditionally conceptualized as a pelvic lesion–centered disease; however, mounting evidence indicates it is a chronic, systemic, and multifactorial inflammatory disorder. This review examines the molecular dialog between ectopic endometrial tissue, the immune system, and peripheral organs, highlighting mechanisms that underlie disease chronicity, symptom variability, and therapeutic resistance. Ectopic endometrium exhibits distinct transcriptomic and epigenetic signatures, disrupted hormonal signaling, and a pro-inflammatory microenvironment characterized by inflammatory mediators, prostaglandins, and matrix metalloproteinases. Immune-endometrial crosstalk fosters immune evasion through altered cytokine profiles, extracellular vesicles, immune checkpoint molecules, and immunomodulatory microRNAs, enabling lesion persistence. Beyond the pelvis, systemic low-grade inflammation, circulating cytokines, and microRNAs reflect a molecular spillover that contributes to chronic pain, fatigue, hypothalamic–pituitary–adrenal axis dysregulation, and emerging gut–endometrium interactions. Furthermore, circulating biomarkers—including microRNAs, lncRNAs, extracellular vesicles, and proteomic signatures—offer potential for early diagnosis, patient stratification, and monitoring of therapeutic responses. Conventional hormonal therapies demonstrate limited efficacy, whereas novel molecular targets and delivery systems, including angiogenesis inhibitors, immune modulators, epigenetic regulators, and nanotherapeutics, show promise for precision intervention. A systems medicine framework, integrating multi-omics analyses and network-based approaches, supports reconceptualizing endometriosis as a systemic inflammatory condition with gynecologic manifestations. This perspective emphasizes the need for interdisciplinary collaboration to advance diagnostics, therapeutics, and individualized patient care, ultimately moving beyond a lesion-centered paradigm toward a molecularly informed, holistic understanding of endometriosis. Full article

Microparticle detection technology uses materials that can specifically recognize complex biostructures, such as antibodies and aptamers, as trapping agents. The development of antibody production technology and simplification of sensing signal output methods have facilitated commercialization of disposable biosensors, making rapid diagnosis possible. Although this contributed to the early resolution of pandemics, traditional biosensors face issues with sensitivity, durability, and rapid response times. We aimed to fabricate microspaces using metallic materials to further enhance durability of mold fabrication technologies, such as molecular imprinting. Low-damage metal deposition was performed on target protozoa and Norovirus-like particles (NoV-LPs) to produce thin metallic films that adhere to the material. The procedure for fitting the object into the bio structured space formed on the thin metal film took less than a minute, and sensitivity was 10 fg/mL for NoV-LPs. Furthermore, because it was a metal film, no decrease in reactivity was observed even when the same substrate was stored at room temperature and reused repeatedly after fabrication. These findings underscore the potential of integrating stable metallic structures with bio-recognition elements to significantly enhance robustness and reliability of environmental monitoring. This contributes to public health strategies aimed at early detection and containment of infectious diseases. Full article

Mobile edge-AI plant monitoring systems enable automated disease control in greenhouses and open fields, reducing dependence on manual inspection and the variability of visual diagnostics. This paper proposes a lightweight two-stage edge-AI system for strawberries, in which a YOLOv10n detector on board a mobile agricultural robot locates leaves affected by seven common diseases (including Leaf Spot) with real-time capability on an embedded platform. Patches are then automatically extracted for leaves classified as Leaf Spot and transmitted to the second module—a compact MobileViT-S-based classifier with ordinal output that assesses the severity of Leaf Spot on three levels (S1—mild, S2—moderate, S3—severe) on a specialised set of 373 manually labelled leaf patches. In a comparative experiment with lightweight architectures ResNet-18, EfficientNet-B0, MobileNetV3-Small and Swin-Tiny, the proposed Ordinal MobileViT-S demonstrated the highest accuracy in assessing the severity of Leaf Spot (accuracy ≈ 0.97 with 4.9 million parameters), surpassing both the baseline models and the standard MobileViT-S with a cross-entropy loss function. On the original image set, the YOLOv10n detector achieves an mAP@0.5 of 0.960, an F1 score of 0.93 and a recall of 0.917, ensuring reliable detection of affected leaves for subsequent Leaf Spot severity assessment. The results show that the “YOLOv10n + Ordinal MobileViT-S” cascade provides practical severity-aware Leaf Spot diagnosis on a mobile agricultural robot and can serve as the basis for real-time strawberry crop health monitoring systems. Full article