Search Results (371)

Mitomycin C (MMC) is a widely employed chemotherapeutic agent, particularly in non-muscle invasive bladder cancer (NMIBC), where it functions by inducing DNA cross-linking and promoting tumor cell apoptosis. However, the tumor microenvironment (TME) significantly influences the therapeutic efficacy of MMC. Among the key regulators within the TME, the complement system and the coagulation pathway play a crucial role in modulating immune responses to cancer therapies, including MMC. This article explores the interaction between platinum nanoparticles (PtNPs) with human serum (HS) of NMIBC patients (T1 and Ta subtypes) at three different points: before the chemotherapy instillation of MMC (t₀) and three (t₃) and six months (t₆) after the treatment with MMC. This novel nanoproteomic strategy allowed the identification of a TME proteomic signature associated with the response to MMC treatment. Importantly, two proteins involved in the immune response were found to be deregulated across all patients (T1 and Ta subtypes) during MMC treatment: prothrombin (F2) downregulated and complement component C7 (C7) upregulated. By understanding how these biomarker proteins interact with MMC treatment, novel therapeutic strategies can be developed to enhance treatment outcomes and overcome resistance in NMIBC. Full article

Non-celiac villous atrophy (NCVA) is a multifaceted and under-recognized clinical entity with an etiology beyond celiac disease. This review critically examines the diverse pathophysiological mechanisms underlying NCVA, including autoimmune enteropathies, immune deficiency-related disorders, infectious processes, drug-induced trauma, and metabolic or environmental influences. A comprehensive synthesis of peer-reviewed literature, clinical studies, and case reports was conducted, adopting a multidisciplinary perspective that integrates immunologic, infectious, metabolic, and pharmacologic insights. The literature search was performed in three phases: identification of relevant studies, critical assessment of selected publications, and synthesis of key findings. Searches were carried out in PubMed, Scopus, Web of Science, and Google Scholar databases. The final search, completed in June 2025, included international, English-language articles, electronic books, and online reports. Studies were included if they addressed NCVA in the context of pathophysiology, clinical manifestations, or management strategies, with priority given to publications from the last ten years (2015–2025). The search strategy used the primary term “non-celiac villous atrophy” combined with supplementary keywords such as autoimmune enteropathy, common variable immunodeficiency, tropical sprue, drug-related enteropathy, pathophysiology, immunological mechanisms, chronic inflammation, genetic factors, environmental influences, and clinical management. Histopathological evaluations reveal that NCVA often manifests with varying degrees of villous blunting, crypt hypertrophy, and intraepithelial lymphocytosis, albeit without the gliadin-specific immune response seen in celiac disease. Various immune pathways are involved, such as autoimmune deregulation and chronic inflammatory responses, while drug-induced and environmental factors further complicate its clinical picture. These findings highlight significant diagnostic challenges and underscore the need to adapt diagnostic algorithms that combine clinical history, serologic evaluations, and histopathologic analysis. In conclusion, an in-depth understanding of the heterogeneous etiology of NCVA is critical to improving diagnostic accuracy and optimizing therapeutic strategies. Future research should prioritize the identification of specific biomarkers and the development of targeted interventions to address the unique mechanisms underlying NCVA, thereby improving patient management and outcomes. Full article

Parkinson’s disease (PD) is the second most common neurodegenerative disease. It primarily affects the motor system but is also associated with a range of cognitive impairments that can manifest early in disease progression, indicating its multifaceted nature. In this paper, we performed a meta-analysis of transcriptomics and proteomics data using MultiOmicsIntegrator to gain insights into the post-transcriptional modifications and deregulated pathways associated with this disease. Our results reveal differential isoform usage between control and PD patient brain samples that result in enriched alternative splicing events, including an extended UTR length, domain loss, and the upregulation of non-coding isoforms. We found that Inositol-Requiring Enzyme 1 (IRE1) is active in PD samples and examined the role of its downstream signaling through X-box binding mRNA 1 (XBP1) and regulated IRE1-dependent decay (RIDD). We identified several RIDD candidates and showed that the enriched alternative splicing events observed are associated with RIDD. Moreover, in vitro mRNA cleavage assays demonstrated that OSBPL3, C16orf74, and SLC6A1 mRNAs are targets of IRE1 RNAse activity. Finally, a pathway enrichment analysis of both XBP1s and RIDD targets in the PD samples uncovered associations with processes such as immune response, oxidative stress, signal transduction, and cell–cell communication that have previously been linked to PD. These findings highlight a potential regulatory role of IRE in PD. Full article

Cervical cancer remains a global health burden, with persistent infection by high-risk human papillomaviruses (HR-HPVs) being the primary etiological factor. HR-HPVs target stem-like cells of the cervical epithelium to establish chronic infections. Upon infection of the cervical transformation zone (TZ)—a region adjacent to the squamocolumnar junction (SCJ)—these viruses drive neoplastic transformation, which is due in part to the unique cellular composition and hormonal responsiveness of the TZ. Reserve cells, which can accumulate at the cervical crypt entrances of the TZ, are thought to be highly susceptible to HR-HPV infection because of their location beneath a single layer of columnar cells. Infection of the stratified ectocervical epithelium, in contrast, requires a wound to allow basal cell infection, replication, and the expression of early genes to adjust epithelial homeostasis while facilitating immune evasion. Persistent infection by HR-HPV types, particularly HPV16 and HPV18, can result in the deregulated expression of viral genes E6 and E7, driving cell cycle disruption, genomic instability, and subsequent viral genome integration. Differences in the microenvironment and transcriptional environment of the ectocervix compared with the TZ could explain the frequent deregulation of E6 and E7 at the latter site, which can drive disease progression towards cancer. Full article

Sickle cell disease (SCD) is the most common hemoglobinopathy, caused by a mutation in the β-globin gene of hemoglobin. It predisposes patients to painful Vaso-occlusive crises (VOC) and multi-organ dysfunctions. The disease exhibits significant phenotypic variability, making it challenging to predict severity and outcomes. This study aimed to characterize the whole blood gene expression profile of Bahraini SCD patients, identifying differentially expressed genes during steady-state (n = 10) and VOC (n = 10) compared to healthy controls (n = 8). Analysis revealed 2073 and 3363 dysregulated genes during steady-state and VOC, respectively, compared to controls, with 1078 genes differentially expressed during VOC versus steady-state. Gene Ontology (GO) enrichment analysis highlighted significant deregulation in immune and hematopoietic pathways, including down-regulation of critical genes for immune modulation and hematopoietic balance. Notably, the transcription factor RUNX3, involved in immune cell differentiation and inflammation, was among the 668 down-regulated genes. RUNX3 was four-fold down-regulated in microarray analysis, three-fold in PCR, and showed a mean protein concentration of 11.13 pg/mL during VOC compared to 457.93 pg/mL during steady-state (p < 0.01). These findings suggest that RUNX3 may serve as a potential biomarker for VOC. Future large-scale validation, additional proteomic studies, and functional investigations are recommended to confirm its clinical utility and significance. Full article

The large portion of the eukaryotic genomes was considered non-functional and called the “dark matter” of the genome, now appearing as regulatory hubs coding for RNAs without the potential for making proteins, known as non-coding RNA. Long non-coding RNA (lncRNA) is defined as functional RNA molecules having lengths larger than 200 nucleotides without the potential for coding for proteins. Thousands of lncRNAs are identified in different plants and animals. LncRNAs are characterized by a low abundance, fewer exons than mRNA, tissue-specific expression, and low sequence conservation compared to protein-coding genes (PCGs). LncRNAs, like PCGs, are regulated by promoters and enhancers with characteristic chromatin signatures, DNA methylation, multiple exons, introns, and alternate splicing. LncRNAs interact with DNA, mRNA, microRNA, and proteins, including chromatin/histone modifiers, transcription factors/repressors, epigenetic regulators, spliceosomal, and RNA-binding proteins. Recent observations indicate that lncRNAs code for small peptides, also called micropeptides (<100 amino acids), and are involved in the development and growth of plants, suggesting the bi-functional activities of lncRNAs. LncRNAs have emerged as the major regulators of diverse functions, principally by altering the transcription of target genes. LncRNAs are involved in plant growth, development, immune responses, and various physiological processes. Abiotic, biotic, nutrient, and other environmental stresses alter the expressions of numerous lncRNAs. Understanding the mechanisms of actions of lncRNAs opens up the possibility of improving agronomic traits by manipulating lncRNAs. However, further studies are required in order to find the interactions among the deregulated lncRNAs and validate the findings from high-throughput studies to harness their potential in crop improvement. Full article

Deregulation of microRNAs (miRNAs) has been implicated in the development of inflammatory bowel disease (IBD). Specific miRNAs are differentially expressed in patients with IBD compared to healthy individuals. Regulation of their expression can modulate the inflammatory response, the composition of the intestinal microbiota, and intestinal barrier function. miRNAs can regulate the immune and inflammatory response via multiple mechanisms, from Th1/Th17 regulation and ferroptosis to modulation of NLRP3 (NOD-like receptor family, pyrin domain-containing 3) and control of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway. The use of miRNAs as biomarkers and therapeutic targets may help monitor IBD treatment and support the development of new, more individualized therapies that minimize common side effects. Full article

Aquaculture has been rapidly growing during the past decade to accommodate the increasing need for seafood as a vital source of nutrients for human beings. The nutritional benefits of incorporating fish into one’s diet are paramount in promoting overall health, bolstering immunity and warding off diseases. Nonetheless, farm-raised aquatic species are frequently subjected to elevated contamination levels due to pesticides, antibiotics, and heavy metals in the marine environment. Pesticides affect fish differently based on species, class, dosage, and exposure duration. They can induce histological damage or neurobehavioral changes by inhibiting acetylcholinesterase production. This can promote liver dysfunction, metabolism deregulation, oxidative stress, and hematological imbalances, impair immune responses, and adversely affect fish reproduction. Furthermore, pesticides negatively affect the nutritional composition of fish by reducing the total protein levels in muscle, liver, gills, and kidney tissues. They disrupt lipid metabolism, resulting in lipid accumulation in the liver and a decrease in polyunsaturated fatty acids. Additionally, pesticides interfere with metabolism by altering carbohydrate levels in the gills, muscles, and kidneys while decreasing glycogen storage in the liver. Pesticide exposure has been linked to severe health impacts in humans, such as non-communicable diseases, reproductive issues, cognitive dysfunction, and cancer. The current review comprehensively emphasizes the harmful effects of pesticides on fish and human health, urging the establishment of environmental monitoring programs and biomonitoring studies. It accentuates the need for risk assessment models to evaluate pesticide impacts on marine ecosystems and advocates for stricter safety standards and lower pesticide residue limits in aquaculture products. Full article

There is currently a worldwide trend towards deregulating the use of genome-edited plants. Virus-induced genome editing (VIGE) is a novel technique that utilizes viral vectors to transiently deliver clustered regularly interspaced short palindromic repeat (CRISPR) components into plant cells. It potentially allows us to obtain transgene-free events in any plant species in a single generation without in vitro tissue culture. This technology has great potential for agriculture and is already being applied to more than 14 plant species using more than 20 viruses. The main limitations of VIGE include insufficient vector capacity, unstable expression of CRISPR-associated (Cas) protein, plant immune reaction, host specificity, and reduced viral activity in meristem. Various solutions to these problems have been proposed, such as fusion of mobile elements, RNAi suppressors, novel miniature Cas proteins, and seed-borne viruses, but the final goal has not yet been achieved. In this review, the mechanism underlying the ability of different classes of plant viruses to transiently edit genomes is explained. It not only focuses on the latest achievements in virus-induced editing of crops but also provides suggestions for improving the technology. This review may serve as a source of new ideas for those planning to develop new approaches in VIGE. Full article

Background: Human leukocyte antigen class I (HLA-I) plays a pivotal role in shaping anti-tumour immunity by influencing the functionality of T cells and natural killer (NK) cells within the tumour microenvironment. Methods: Here, we explored the transcriptional landscape of HLA-I molecules across various solid cancer transcriptomes from The Cancer Genome Atlas (TCGA) database and assessed the impact of HLA-I expression on the clinical significance of tumour-infiltrating CD56^dim and CD56^bright NK cells. Results: Our analysis revealed that high HLA-I expression correlated with reduced patient survival in the TCGA lower-grade glioma (LGG) cohort, with this association varying by histopathological subtype. We then estimated the relative abundance of 23 immune and stromal cell signatures in LGG transcriptomes using a cellular deconvolution approach, which revealed that LGG patients with low HLA-I expression and high CD56^dim NK cell abundance had better survival outcomes compared to those with high HLA-I expression and low CD56^dim NK cell abundance. Furthermore, HLA-I expression was positively correlated with various inhibitory NK cell receptors and negatively correlated with activating NK cell receptors, particularly those within the killer cell lectin-like receptor (KLR) gene family. High co-expression of HLA-E and NKG2A predicted poor survival outcomes in LGG patients, whereas low HLA-E and high NKG2C/E abundance predicted more favourable outcomes, suggesting a potential modulatory role of HLA-I on the tumour-infiltrating cytotoxic CD56^dim NK cell subset. Conclusions: Overall, our study unveils a potential role for deregulated HLA-I expression in modulating the clinical impact of glioma-infiltrating CD56^dim NK cells. These findings lay the foundation for future in-depth experimental studies to investigate the underlying mechanisms. Full article

Systemic molecular responses to pathogen-associated molecular patterns and their modulation by antioxidants are poorly understood in humans. Here, we present a two-stage clinical interventional study in healthy humans challenged with lipopolysaccharide. In the first step, the kinetics of inflammatory modulators within 8 h were investigated by plasma proteomics and lipidomics. In a second step, the effects of a placebo-controlled antioxidant intervention on the individual responses prior to another lipopolysaccharide challenge were determined. Plasma proteomics revealed an early involvement of the endothelium and platelets, followed by the induction of liver-derived acute phase proteins and an innate immune cell response. Untargeted lipidomics revealed an early release of fatty acids and taurocholic acid, followed by complex regulatory events exerted by oxylipins. The consistent lipopolysaccharide-induced downregulation of lysophospholipids suggested the involvement of the Lands cycle, and the downregulation of deoxycholic acid reinforced emerging links between the inflammasome and bile acids. Groups of molecules with similar kinetics to lipopolysaccharide challenge were observed to share precursors, synthesizing enzymes or cellular origin. Dietary antioxidant supplementation prior to lipopolysaccharide challenge had no detectable effect on protein kinetics but significantly downregulated pro-inflammatory sphingosine-1-phosphate and increased levels of oxylipins, 20-HEPE, and 22-HDoHE, which have been described to facilitate the resolution of inflammation. The present study identified a complex network of lipid mediators deregulated in plasma upon lipopolysaccharide challenge and highlighted the role of platelets, endothelial cells, and erythrocytes as potential inflammatory modulators. While dietary antioxidant supplementation hardly affected the initiation of inflammation, it may exert its effects supporting the resolution of inflammation. Full article

Gulf War Illness (GWI) is a multi-symptom disorder affecting 1990–1991 Persian Gulf War veterans and is characterized by post-exertional malaise, neurological symptoms, immune deregulation, and exhaustion. Causation is not understood, and effective diagnostics and therapies have not yet been developed. In this work, we analyzed stress-related, sex-specific transcriptomic shifts in GWI subjects and healthy controls through RNA sequencing of peripheral blood mononuclear cells (PBMCs). Blood samples at baseline (T0), at maximal exertion (T1), and four hours post-exertion (T2) were analyzed. In female subjects with GWI, pathways associated with pro-inflammatory processes were found to be deregulated, and in male GWI subjects, pathways related to IL-12 signaling and lymphocytic activation were deregulated at T1 compared to T0. During recovery from stress, pathways corresponding to immune responses and microglial cell activation were altered in female GWI subjects, and apoptotic signaling changed in males with GWI. Documented sex-specific immune deregulation leads to finding better biomarkers. Targeting sex-specific transcriptomic markers of the disease could lead to new therapies for GWI. Full article

Nck-associated protein 1 (NCKAP1) is critical for cytoskeletal functions and various cellular activities, and deregulation of NCKAP1 in many cancers significantly influences the outcomes of malignant diseases. However, the functions of NCKAP1 in the progression of renal cancer are yet unknown. To investigate the specific roles of NCKAP1 in the immune regulation and tumor progression of renal cancer, the expression of NCKAP1 and genetic variations were analyzed across cancer types at different pathological stages via UALCAN and cBioPortal. Immune cell infiltration in renal cancer was also assessed by ssGSEA and single-cell gene expression data from the GEO. RNA sequencing of NCKAP1-overexpressing 769P cells further examined the impact of NCKAP1 on kidney cancer. Our pancancer analyses revealed a complex NCKAP1 expression profile across various cancer types, with reduced levels in renal cancer patients linked to patient prognosis. CIBERSORT and single-cell RNA sequencing revealed the expression patterns of NCKAP1 in different cell lineages in renal cancer and a significant correlation between NCKAP1 and immune cell infiltration in the kidney tumor microenvironment. We further verified that NCKAP1 suppressed cancer cell growth and affected tumor development in renal cancer via the PI3K/AKT/mTOR signaling pathway. Our results indicate that NCKAP1 is a potential predictive marker and treatment target for renal cancer. Full article

Despite being the leading cause of death worldwide, cancer still lacks precise biomarkers for effective targeting, limiting efforts to reduce mortality rates. This review explores the role and clinical significance of a newly identified long non-coding RNA, MYOSLID, in cancer progression. MYOSLID has emerged as a critical modulator in cancer progression by influencing key hallmarks such as proliferation, immune evasion, metastasis, and metabolic reprogramming. It promotes tumor cell growth by stabilizing hypoxia-inducible factor 1 and acting as a competing endogenous RNA (ceRNA) to sequester tumor-suppressive microRNAs like miR-29c-3p, thereby enhancing oncogene expression. It facilitates immune evasion by upregulating PD-L1, suppressing T cell activation, and modulating necroptosis pathways involving RIPK1 and RIPK3. Additionally, MYOSLID drives metastasis by regulating epithelial–mesenchymal transition markers such as LAMB3 and Slug while promoting RAB13-mediated cytoskeletal remodeling and enhancing cancer cell invasion. We have obtained the expression of MYOSLID from TCGA and the ENCORI database. The expression of colorectal adenocarcinoma (COAD) and head and neck squamous cell carcinoma (HNSCC) is associated with poor prognosis and lower survival rate. Given its significant potential as a diagnostic biomarker and therapeutic target, further research is required to elucidate its precise molecular mechanisms and therapeutic applications in cancer treatment. Full article

A growing number of systemic hereditary inflammatory diseases characterized by periodic fevers and elevated acute-phase proteins during flares has been linked to deregulated inflammasome function and excessive bioactivity of interleukin (IL)-1. All these conditions respond, at varying degrees, to the specific blockade of IL-1. The remarkable progress with IL-1 antagonists in treating hereditary inflammasome-based disorders has offered new hope for several patients with further non-hereditary autoinflammatory conditions from multifactorial backgrounds. The effectiveness of the IL-1 blockade has transformed our understanding and management of many complex diseases and highlighted the role of aberrant IL-1 signaling in enigmatic conditions, characterized by recurrent or continuous inflammation and a lack of a role for autoreactive T-cells or autoantibody production. To date, the long-term blockade of IL-1 has been found to restore the clinical equilibrium in systemic inflammasomopathies of childhood, and IL-1 inhibitors have become cardinal weapons in managing both monogenic innate immunity defects and a plethora of polygenic diseases occurring in children, including Still’s disease, Kawasaki disease, recurrent pericarditis, chronic non-bacterial osteomyelitis, and Behçet’s disease. Very few side effects have been reported with the long-term use of anakinra, rilonacept, or canakinumab, and their safety profile has been largely documented even in childhood. Further investigations into the role of inflammasomes in the pathogenesis of autoimmune conditions as well as brain degenerative or cardiovascular disorders can be expected, paving the way for precision medicine with benefits beyond inhibiting signaling by individual IL-1-family cytokines. Full article