Search Results (9,728)

COVID-19 has resulted in over 777 million confirmed cases and more than 7 million deaths globally. While vaccination offers protection for individuals with a functional immune system, immunocompromised populations will not generate sufficient responses, highlighting the critical need for new antiviral treatments. Here we evaluated four highly conserved anti-COVID siRNAs targeting the ORF1a-Nsp1, Membrane, and Nucleocapsid regions by identifying their antiviral efficacy in vitro and investigated the direct delivery of naked siRNAs to the respiratory tract of mice via intranasal instillation to provide proof-of-concept evidence of their in vivo antiviral activity. Dose-response analysis of siRNAs revealed a range of IC50 0.02 nM to 0.9 nM. Intranasal administration of naked anti-COVID siRNA-18 in a K18-hACE2 transgenic SARS-CoV-2 mouse model was capable of reducing viral mRNA levels and disease severity. While anti-COVID siRNA-30 induced modest interferon-stimulated gene expression in vitro and immune cell infiltration in vivo, these effects were markedly reduced by 2′-O-methyl-AS456 chemical modification, which preserved antiviral efficacy against SARS-CoV-2 while minimizing off-target immune activation. These results demonstrate the feasibility of direct respiratory siRNA administration for in vivo viral suppression and highlight the benefit of using conserved target sequences and chemical modification to enhance therapeutic safety and efficacy. Full article

Background: Celiac disease (CD) is a systemic autoimmune disorder triggered by gluten exposure in genetically predisposed individuals. Beyond gastrointestinal symptoms, CD is increasingly recognized to affect extraintestinal organs, including the eye. Methods: A PubMed, Cochrane, Web of Science, and Scopus databases search up to April 2025 was conducted to identify studies on ocular involvement in CD. Results: Large population-based cohorts have demonstrated an increased risk of cataract and uveitis in individuals with CD. Cross-sectional and case–control studies further report reduced tear break-up time and decreased Schirmer test values, indicating tear film instability and associated ocular surface abnormalities. Additional findings include reduced anterior chamber depth and volume, alterations in subfoveal and peripapillary choroidal thickness, thinning of the retinal nerve fiber layer, and microvascular changes such as reduced superficial and deep capillary plexus densities. Furthermore, deficiencies of vitamins A, D, B12, and iron have been consistently associated with structural and functional ocular alterations, underscoring the contribution of impaired nutrient absorption. Conclusions: Ocular involvement in CD likely reflects the interplay of immune dysregulation, nutritional deficiencies, and microvascular alterations. Ophthalmic referrals should be considered in CD patients presenting with ocular symptoms. Early recognition and regular monitoring may facilitate timely diagnosis, improve visual outcomes, and support normal ocular development. Full article

The complex relationship between human cytomegalovirus (HCMV) and cancer has been of interest since the 1960s. As a highly prevalent human β-herpesvirus, HCMV establishes lifelong latency in CD34+ myeloid progenitor cells and has been implicated as an oncomodulatory virus in various cancers, including glioblastoma multiforme, breast, prostate, colorectal, and ovarian cancer (OC). Recently, discussions have emerged regarding the classification of HCMV as an eighth oncovirus due to the persistence of its nucleic acids and proteins in many tumour types. As one of the deadliest gynaecological cancers, OC is often characterised as the ‘silent killer’ with less than half of women surviving for 5 years, a rate that drops below 20% when detected at advanced stages. Reported effects of HCMV vary between cancers, likely due to differences in tumour type, viral strain, and disease stage. While HCMV infection has been linked to poor OC patient outcomes, its impact on the OC tumour microenvironment (TME) and immune system remains less understood. Investigating HCMV’s potential oncogenic role could provide critical insights into OC progression. This review discusses recent developments on HCMV’s multifaceted roles in OC, including strain heterogeneity, immunomodulation of the TME, dysregulation of inflammatory signalling pathways, and potential therapeutic approaches targeting HCMV in anti-cancer immunotherapies. Full article

Background/Objectives: Hodgkin’s lymphoma (HL) is a cancer of the lymphatic system, the etiology of which remains partially unexplained, and environmental factors, including nutritional factors, may play an important role in its development and clinical course. The aim of this review was to examine the available literature on the impact of nutrition on the development and mortality of Hodgkin lymphoma. Methods: We conducted a literature review using databases, including publications from the last 10 years on nutrition and HL. Eventually, 3 publications were included in the review. Conclusions: Available data suggest that a diet rich in vegetables, fruits, fiber, and omega-3 fatty acids may have a protective effect, reducing the risk of developing Hodgkin’s lymphoma and improving prognosis and survival through anti-inflammatory and immune-supporting effects. On the other hand, excessive consumption of saturated fats, simple sugars and processed meat products can promote cancer transformation and worsen the course of the disease. Despite the promising results, further, well-designed prospective and interventional studies are needed to unequivocally determine the role of nutrition in the etiopathogenesis and treatment of HL. Full article

Priasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation, impaired differentiation, and dysregulated immune responses. Emerging evidence highlights the central role of keratinocytes as immune-competent cells that integrate signals from cytokines, metabolic cues, the gut–skin axis, and the tissue microenvironment. Key intracellular signaling pathways, including NF-κB, JAK/STAT, MAPK, and PI3K/AKT/mTOR, along with the IL-23/IL-17 axis, orchestrate keratinocyte-mediated inflammation and epidermal hyperplasia. Metabolic factors, nutrients, and redox balance further modulate these responses, while the intestinal microbiota and its metabolites, such as short-chain fatty acids, shape systemic and cutaneous inflammation. This review offers a critical, integrated perspective, that moves beyond descriptive summaries. We propose a conceptual framework in which the keratinocyte metabolic state, particularly the sirtuin/NAD+ axis, acts as a crucial convergence point for systemic nutritional, microbial, and inflammatory signals. Targeting sirtuins and associated pathways with natural or synthetic modulators represents a promising, host-centric strategy to restore keratinocyte function and reduce chronic inflammation. This synthesis underscores the potential of combining molecular, metabolic, microbial, and nutritional insights to develop personalized and effective approaches for psoriasis management.  Full article

Background: Microglial cells are the resident immune cells in the central nervous system (CNS) and constitute the brain’s innate immune system. They are the smallest of the glial cells and are derived from phagocytic white blood cells, fetal monocytes, which migrate from the blood into the brain during development. On the other hand, epilepsy is a chronic condition defined as recurrent unprovoked seizures, with at least two seizures occurring over 24 h apart. Methods: To determine the role of microglial activation in the pathogenesis of drug-resistant epilepsy, we systematically searched published data for biomarkers of microglial activation from main databases including PubMed, PubMed Central, Scopus, Embase, Google Scholar, and Medline. Two research registries were also searched: the Cochrane Registry and clinicaltrial.gov. Data was collected after applying inclusion and exclusion criteria and studies were appraised critically. Both Medical Subject Headings (MeSH) and regular keyword search strategies were employed. Results: Our systematic review shows significant elevation of biomarkers of microglial activation in patients with drug-resistant epilepsy, suggesting its role in the disease’s pathogenesis. Conclusions: Microglia cells are therefore considered as a special type of mononuclear phagocytes found in the CNS that plays important roles in both the brain’s immunity and homeostatic functions. The role of microglial activation in the pathogenesis of drug-resistant epilepsy is an active area of study, with potential therapies for drug-resistant epilepsy that target microglia currently being investigated. Full article

Demyelinating diseases comprise a group of chronic and debilitating neurological disorders, with the destruction of the myelin sheath serving as the core pathological hallmark. The central pathogenesis involves immune-mediated damage to oligodendrocytes (Ols) and myelin breakdown, accompanied by a vicious cycle of neuroinflammation and impaired epigenetic repair. Current therapeutic strategies, including conventional immunomodulatory agents to targeted monoclonal antibodies, effectively control disease relapses but exhibit limited efficacy in promoting neural repair. Consequently, research focus is increasingly shifting towards neuroprotective and remyelination strategies. In this context, Emerging therapeutic promise stems primarily from two fronts: the advent of novel pharmaceuticals, such as remyelination-promoting drugs targeting oligodendrocyte maturation, interventions inhibiting epigenetic silencing, signal pathway inhibitors, and natural products derived from traditional Chinese medicine; the development of innovative technologies, including cell therapies, gene therapy, exosome and nanoparticle-based drug delivery systems, as well as extracellular protein degradation platforms. Nevertheless, drug development still faces challenges such as disease heterogeneity, limited blood–brain barrier penetration, long-term safety, and difficulties in translating findings from preclinical models. Future efforts should emphasize precision medicine, multi-target synergistic therapies, and the development of intelligent delivery systems, with the ultimate goal of achieving a paradigm shift from delaying disability progression to functional neural reconstruction. Full article

The mud crab (Scylla paramamosain), an economically important crustacean aquaculture species in southern China, is susceptible to infections due to its immune system lacking acquired immunity. An emergent disease locally termed “pus crab” has caused severe muscle lesions in pond-farmed crabs, but its etiology remained unclear. Here, we applied an integrated approach, histopathology, electron microscopy, metagenomic sequencing, and experimental infection to identify the pathogen of “pus crab”. Histological staining (H&E, Wright–Giemsa, and Masson) revealed muscle fiber dissolution, disordered fiber arrangement, and abundant interstitial spore-like bodies. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed intracellular spore morphology consistent with microsporidia. Metagenomic profiling showed a pronounced shift in the muscle microbiome, with a marked increase in microsporidian taxa at the genus level and a concurrent decline in bacterial relative abundance. Functional annotation indicated enrichment of pathways related to protein processing, ribosome biogenesis, glycosylation, and the ubiquitin–proteasome system. Isolation of spores from diseased muscle and subsequent injection into healthy crabs reproduced wild-like clinical signs and histopathology, confirming infectivity and implicating microsporidia as the likely etiological agents of “pus crab”. These findings establish a multidisciplinary framework for pathogen identification in aquaculture and provide candidate molecular and biochemical markers for early diagnosis and management. Full article

Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to be a leading cause of death from a single infectious agent worldwide. Conventional antibiotic therapies face significant limitations, including multidrug resistance, poor treatment adherence, limited penetration into granulomas, and systemic toxicity. Recent advances in nanomedicine have paved the way for nanotheranostic approaches that integrate therapeutic, diagnostic, and preventive functions into a single platform. Nanotheranostic systems enable targeted drug delivery to infected macrophages and granulomatous lesions, real-time imaging for disease monitoring, and controlled, stimuli-responsive release of antitubercular agents. These platforms can be engineered to modulate host immune responses through host-directed therapies (HDTs), including the induction of autophagy, regulation of apoptosis, and macrophage polarization toward the bactericidal M1 phenotype. Additionally, nanocarriers can co-deliver antibiotics, immunomodulators, or photosensitizers to enhance intracellular bacterial clearance while minimizing off-target toxicity. The review also discusses the potential of nanotechnology to improve TB prevention by enhancing vaccine efficacy, stability, and targeted delivery of immunogens such as BCG and novel subunit vaccines. Key nanoplatforms, including polymeric, lipid-based, metallic, and hybrid nanoparticles, are highlighted, along with design principles for optimizing biocompatibility, multifunctionality, and clinical translatability. Collectively, nanotheranostic strategies represent a transformative approach to TB management, bridging diagnosis, therapy, and prevention in a single, adaptable platform to address the unmet needs of this global health challenge. Full article

The development of novel therapeutics for deadly diseases such as glioblastoma (GBM) is bottlenecked by poor preclinical models. GBM is the most common and deadliest primary brain tumor in adults, with an average prognosis of 12–15 months, primarily due to its high cellular heterogeneity and treatment resistance from GBM stem cells. The advancement of in vitro models into organoids, three-dimensional tissue-like modeling systems, has been a promising approach to improving translational medicine for GBM. However, the critical tradeoff between technical convenience and physiological relevance threatens the integrity and reproducibility of GBM organoid (GBO) biomanufacturing. This comprehensive review breaks down and discusses the key features of GBM tumor microenvironment (TME), traces the advancement of in vitro models from two-dimensional cultures to three-dimensional stem cell-derived GBOs, evaluates the process through an engineering perspective (genetic, biochemical, biophysical, and process engineering), and addresses critical translational gaps. Reviewing trends over the last fifteen years in biomanufacturing approaches to GBOs revealed fundamental oversights that address previous review focuses on the limitations of organoids (i.e., maturity, vasculature, and immune defense). To summarize, GBO’s translational gap and reproducibility challenges are rooted in the prioritization of technical convenience over physiological relevance. To achieve clinical relevance, future GBO development must focus on transitioning to fully defined components (excluding animal-derived ECM), developing sufficiently large-sized constructs to recapitulate the full TME, and integrating non-destructive and enhanced functional readouts of the GBOs. Full article

Ovarian cancer is the sixth leading cause of cancer-related deaths among women in the United States. This complex disease arises from tissues such as the ovarian surface epithelium, fallopian tube epithelium, endometrium, or ectopic Müllerian components and is characterized by diverse histological and molecular traits. Standard treatments like surgery, chemotherapy, and radiation have limited effectiveness and high toxicity. Targeted therapies, including poly (ADP-ribose) polymerase PARP inhibitors, anti-angiogenics, and immune checkpoint inhibitors (ICIs), face obstacles such as adaptive resistance and microenvironmental barriers that affect drug delivery and immune responses. Factors in the tumor microenvironment, such as dense stroma, hypoxia, immune suppression, cancer stem cells (CSCs), and angiogenesis, can reduce drug efficacy, worsen prognosis, and increase the risk of recurrence. Research highlights impaired immune function in ovarian cancer patients as a contributor to recurrence, emphasizing the importance of immunotherapies to target tumors and restore immune function. Preclinical studies and early clinical trials found that natural killer (NK) cell-based therapies have great potential to tackle ovarian tumors. This review explores the challenges and opportunities in treating ovarian cancer, focusing on how NK cells could help overcome these obstacles. Recent findings reveal that engineered NK cells, unlike their primary NK cells, can destroy both stem-like and differentiated ovarian tumors, pointing to their ability to target diverse tumor types. Animal studies on NK cell therapies for solid cancers have shown smaller tumor sizes, tumor differentiation in vivo, recruitment of NK and T cells in the tumor environment and peripheral tissues, restored immune function, and fewer tumor-related systemic effects—suggesting a lower chance of recurrence. NK cells clinical trials in ovarian cancer patients have also shown encouraging results, and future directions include combining NK cell therapies with standard treatments to potentially boost effectiveness. Full article

Background: Neurocysticercosis is a parasitic infection of the central nervous system caused by the larval stage of Taenia solium. This disease is endemic in some countries in Central and South America, South and South-East Asia, and sub-Saharan Africa. In North America, Europe, Japan, and Australia, only sporadic cases are documented. Moreover, reports of bacterial superinfection arising within neurocysticercotic lesions remain exceptionally scarce. Methods: We report a clinically severe and diagnostically challenging case of suspected neurocysticercosis with cerebral streptococcal superinfection in a 17-year-old Italian patient with Down syndrome and no history of travel to endemic regions. Results: The patient, with pre-existing epileptic encephalopathy, presented with progressive drowsiness and altered mental status, rapidly deteriorating to cardiorespiratory arrest. Neuroimaging demonstrated multiple ring-enhancing lesions, in conjunction with positive Taenia solium serology. Streptococcus spp. was identified in one neurosurgically drained lesion, consistent with secondary bacterial involvement in association with concurrent pneumonia. Combined antiparasitic therapy and targeted antimicrobial treatment resulted in sustained clinical and radiological improvement. Conclusions: In non-endemic settings, neurocysticercosis should remain within the differential diagnosis of unexplained epilepsy and multifocal CNS lesions. Although rare, bacterial superinfection warrants consideration in atypical presentations, particularly in individuals with concomitant infectious foci and underlying immune dysfunction such as that associated with Down syndrome. Full article

Background: Interleukin-1 (IL-1) inhibitors are approved for the treatment of various inflammatory diseases associated with immune system abnormalities. However, large-scale real-world studies to assess their security are still limited. Therefore, a pharmacovigilance study was conducted based on the data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods: Adverse events (AEs) linked to IL-1 inhibitors were analyzed using the FAERS database from Q1 2004 to Q3 2024. Risk signals were identified through disproportionality analysis algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). Results: Among 17,670 AE reports where an IL-1 inhibitor was the “primary suspected” drug, 27 significant system organ classes (SOCs) were identified. Notable signals included infections and infestations (ROR: 2.31, 95% CI: 2.25–2.37) and congenital, familial, and genetic disorders (ROR: 2.26, 95% CI: 2.05–2.48). At the preferred term (PT) level, 263 significant AE signals were detected, such as pyrexia (ROR: 5.27, 95% CI: 5.03–5.53), nasopharyngitis (ROR: 2.31, 95% CI: 2.10–2.54), and injection site erythema (ROR: 6.09, 95% CI: 5.67–6.55). Importantly, we also identified less common or previously unreported AEs, including cardiac disorders (e.g., postural orthostatic tachycardia syndrome with anakinra; pulmonary valve incompetence with rilonacept) and endocrine disorders (e.g., secondary adrenocortical insufficiency with canakinumab). Furthermore, 36.33% of cases emerged after more than 360 days of treatment with IL-1 inhibitors. Conclusions: This study revealed real-world safety data on IL-1 inhibitors, providing important insights to enhance the clinical use of IL-1 inhibitors and minimize potential AEs. Full article

Background/Objectives: Pulmonary fibrosis (PF) and lung cancer (LC) are major global health challenges that share several pathogenic mechanisms despite their distinct clinical features. PF leads to progressive fibrotic remodeling and respiratory decline, while LC is characterized by uncontrolled proliferation, invasion, and metastasis. Growing evidence shows that PF markedly increases the risk of LC development. This review aims to clarify the convergent molecular and cellular mechanisms that link fibrogenesis to tumorigenesis. Methods: Published studies exploring shared pathogenic pathways, molecular signaling networks, immune microenvironment alterations, and mitochondrial and genomic disturbances in PF and LC were systematically examined and integrated to identify common mechanisms contributing to fibrosis-associated carcinogenesis. Results: Findings highlight several overlapping processes between PF and LC, including oxidative stress, genomic instability, dysregulated DNA damage repair, immune microenvironment remodeling, mitochondrial dysfunction, and alterations in the ubiquitin–proteasome system. These aberrations drive chronic inflammation, epithelial–mesenchymal transition (EMT), extracellular matrix (ECM) remodeling, and other hallmarks shared by both diseases. Key signaling pathways—such as transforming growth factor-β (TGF-β), programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1), and tumor microenvironment–mediated immune evasion—further contribute to disease progression and increased LC risk in PF patients. Conclusions: Integrating molecular and pathological insights reveals a strong biological continuum between PF and LC. Understanding these convergent mechanisms may facilitate the identification of diagnostic biomarkers and therapeutic targets, ultimately helping to mitigate PF-associated lung carcinogenesis. Full article

Despite advances in blood-based screening tests for colorectal cancer (CRC), most existing assays focus on DNA-based biomarkers, which predominantly reflect tumor-derived fragments released at later disease stages. In contrast, whole-blood transcriptomic profiling can capture systemic immune responses and tumor–host interactions, offering a complementary strategy for earlier disease detection. However, clinically validated whole-blood transcriptomic signatures remain limited. Here, we investigated a whole-blood RNA-based biomarker discovery strategy by integrating multi-cohort transcriptomic resources. Public GEO datasets (GSE164191 and GSE11545) were harmonized and analyzed, yielding 956 differentially expressed genes (DEGs). Multi-layer biological filtering incorporating PPI networks, transcription factors, CRC-related GWAS variants, whole-blood eQTL signals, DigSeE, and CoReCG disease associations refined these to 375 high-confidence transcripts (WB-PADs). In parallel, RNA-seq analysis of a Korean cohort (10 CRC vs. 10 controls) identified 217 DEGs (WB-K). Cross-dataset convergence highlighted seven overlapping transcripts, and five candidates (DLG5, CD177, SH2D1B, NQO2, and KRT73) were selected for validation. RT-qPCR in an independent clinical cohort (106 CRC and 123 healthy controls) confirmed four transcripts with significant discriminatory ability. A multivariable logistic regression model derived from the five-transcript signature achieved an AUC of 0.952 (95% CI 0.884–1.000), with sensitivities of 0.889 and 0.667 at fixed specificities of 90% and 95%, respectively, demonstrating strong applicability for screening-relevant thresholds. Notably, the model retained high accuracy in early-stage CRC (Stage I–II: AUC 0.929, 95% CI 0.868–0.989). Overall, this study provides a robust analytic framework for reproducible whole-blood RNA biomarker discovery and establishes a multi-gene signature with promising translational potential for minimally invasive and early CRC detection. Full article