Search Results (302)

Background/Objectives: Cytochrome 1B1 (CYP1B1) is overexpressed in several cancers, contributing to carcinogenesis, cancer progression, and chemoresistance. Despite its known oncogenic role, its expression in bone sarcomas remains unknown. Methods: This study assessed CYP1B1 expression in osteosarcoma and chondrosarcoma using immunohistochemistry on tissue microarrays and analyzed corresponding transcriptomic profiles from public RNA-seq datasets. Associations with clinicopathological features, survival, drug sensitivity, and protein–protein interaction networks were also investigated. Results: CYP1B1 was overexpressed in 72.3% of bone sarcomas (78% of osteosarcomas and 82.1% of chondrosarcomas) and was significantly underexpressed in normal bone (12.5%, p < 0.001). Importantly, high CYP1B1 expression was found in younger patients (≤34 years; p = 0.013), but no other associations with tumor grade, size, or metastasis were observed. The mean survival rate of CYP1B1-positive patients was insignificantly shorter than that of negative patients (58.8 vs. 62.8 months; p = 0.170). Although not confirmed in the multivariate analysis, CYP1B1-positive patients had poorer survival in the univariate analysis, which may reflect tumor aggressiveness rather than prognostic value. Transcriptomic data showed significantly lower CYP1B1 mRNA in osteosarcoma versus normal bone, suggesting post-transcriptional or translational regulation. Drug sensitivity analysis revealed both positive and negative correlations between CYP1B1 expression and response to various compounds in the GDSC dataset, highlighting potential therapeutic implications. Conclusions: Despite low mRNA levels, CYP1B1 protein is consistently and selectively overexpressed in bone sarcomas, particularly in younger patients. While not prognostic, its expression profile warrants further investigation and evaluation as a therapeutic target or diagnostic biomarker, especially in refractory or advanced cases. Full article

Soft tissue manipulation (STM) is widely used by physical therapists, massage therapists, athletic trainers, and osteopathic physicians to manage musculoskeletal pain, yet its biological mechanisms remain poorly understood. Preclinical studies indicate that STM can alter immune cell behavior in animal models, increasing anti-inflammatory cytokines (IL-4, IL-10) and reducing chemokines such as RANTES/CCL5. Single-cell transcriptomic analyses suggest mechanical treatment may reprogram stromal cells and shift immune cell recruitment in aged or inflamed tissues. However, many of these mechanistic findings have yet to be confirmed in human studies. Early clinical trials show massage therapy can modify circulating leukocytes and reduce cytokine responses, but direct tissue-level evidence in human subjects remains limited. This narrative review summarizes existing insights and emphasizes the need for future clinical investigations targeting populations with chronic inflammation, repetitive-use injuries, post-surgical fibrosis, or age-related muscle decline. We advocate for studies incorporating tissue or fluid sampling, cytokine profiling, and molecular assays such as flow cytometry or transcriptomics to characterize STM’s immunological effects in people. Rather than simply easing symptoms, STM may act as a precision mechanical stimulus that recalibrates immune tone and promotes tissue repair. Bridging basic science with clinical research will be essential to establish STM as a biologically informed, mechanobiology-based therapeutic strategy. Full article

HSV-2 is the main pathogen causing genital herpes, and its infection increases the infection and transmission of HIV-1. Currently, there are no vaccines to prevent HSV-2 infection or treatment that can fully cure it. Mining key host factors that regulate HSV-2 replication and elucidating their specific regulatory mechanisms are crucial for understanding virus–host interactions and discovering new antiviral targets. In the current study, we identified DDX43 as a cellular factor involved in the suppression of HSV-2 replication through comparative transcriptomic analyses of HSV-2-infected epithelial cells, followed by experimental validation. Comprehensive transcriptomic profiling revealed distinct host cellular gene expression patterns in HeLa and ARPE-19 cell lines post HSV-2 infection. Subsequent orthogonal partial least-squares discriminant analysis (OPLS-DA) pinpointed DDX43 as one of the principal mediators distinguishing the host response between HSV-2-infected HeLa and ARPE-19 cells. Furthermore, overexpression of DDX43 inhibited HSV-2 replication, whereas knockdown of endogenous DDX43 enhanced HSV-2 replication. Additional experiments revealed that human DDX43 inhibits HSV-2 replication in an interferon-independent manner. This study demonstrates that DDX43 serves as a host regulator against HSV-2 infection, underscoring the power of comparative transcriptomics in identifying novel host proteins that modulate viral replications. Full article

Citrobacter braakii is an emerging opportunistic pathogen of escalating clinical significance in animal hosts, though its pathogenic mechanisms remain poorly characterized. This study isolated a C. braakii strain (SCGY-1L) from diseased Siniperca chuatsi and confirmed its identity through integrated morphological, physiological, and molecular analyses. Comprehensive genomic sequencing revealed a 5.75 Mb genome comprising one circular chromosome and two plasmids. A Circos plot was constructed to visualize the genomic architecture of strain SCGY-1L, revealing 5482 protein-coding genes, 25 tRNA genes, and 86 rRNA genes. Additionally, 738 virulence-associated genes and 366 antibiotic resistance determinants were annotated, elucidating multidrug-resistant phenotypes including insensitivity to erythromycin and penicillin. Pathogenicity assessment established an LD₅₀ of 1.28 × 10⁶ CFU/mL in infected hosts, with histopathological analysis showing significant hemorrhage and necrosis in target organs (liver, spleen, kidney). Host transcriptome profiling generated 41.21 Gb of high-quality clean data, identifying 2201 differentially expressed genes post-infection (1568 up-regulated; 633 down-regulated). These were significantly enriched in phagocytosis, cytokine-mediated signaling, and inflammatory regulation pathways. These molecular insights establish C. braakii’s mechanistic framework for pathogenesis and host adaptation, providing critical targets for diagnostics and therapeutics against emerging Citrobacter infections. Full article

Goose astrovirus (GAstV) infection has emerged as a prevalent cause of urate deposition and viral gout in major goose farming across China, leading to high mortality and substantial economic losses. However, the molecular mechanisms linking GAstV to gout pathogenesis remain elusive. Here, a total of 10 five-day-old Jiangnan white goslings were selected, and tissue damage and kidney gene expression profiles were investigated. The results showed multi-organ damage in GAstV-infected gosling, including kidney, liver, spleen, and lung. Also, 342 differentially expressed genes were identified in infected kidney tissues after 10 days post-infection using transcriptomic sequencing, including 185 upregulated and 157 downregulated genes. In addition, gene set enrichment analysis revealed significant positive correlations between GAstV infection and bile acid metabolism and fatty acid metabolism pathways. Notably, bile acid metabolism was implicated in uric acid regulation and gout progression. Protein–protein interaction network analysis identified AGXT as a central hub gene within the bile acid metabolic pathway, with key upregulated interactors including PIPOX, ALDH1A1, and CAT. AGXT, a critical enzyme in glyoxylate detoxification, directly modulates uric acid biosynthesis. Our findings propose that GAstV-induced activation of bile acid metabolism, particularly AGXT upregulation, drives hyperuricemia and subsequent gout pathology. This study elucidates a novel mechanism of GAstV-associated metabolic dysregulation and provides actionable genetic targets for antiviral breeding strategies in waterfowl. Full article

Grass carp (Ctenopharyngodon idella), a key species in freshwater aquaculture, is particularly vulnerable to opportunistic pathogens, including Aeromonas hydrophila and Aeromonas veronii. While the pathogenic mechanisms of individual infections have been extensively characterized, the host immune responses during co-infection remain poorly understood. This research explored the renal pathological alterations and transcriptomic shifts in grass carp subjected to simultaneous infection by A. hydrophila and A. veronii. Mortality occurred as early as 24 h post-challenge, ultimately reaching a cumulative death rate of 65%. Quantitative analysis of renal bacterial burden revealed a marked increase in colonization at 3 days post-infection (dpi). The histopathological assessment showed progressive kidney damage, including tubular collapse, epithelial necrosis, interstitial edema, and widespread epithelial desquamation, with the most severe lesions observed at 5 dpi and partial signs of recovery by 7 dpi. A total of 1106 and 472 genes were found to be differentially expressed at 1 and 5 dpi, respectively, based on transcriptome profiling. The functional enrichment analysis indicated that the differentially expressed genes (DEGs) were mainly involved in the complement and coagulation cascade pathways. Notably, the immune-related genes exhibited a biphasic trend, with predominant downregulation at 1 dpi followed by marked upregulation by 5 dpi, indicating dynamic changes in immune modulation during co-infection. These results provide new insights into host responses during dual bacterial infections in fish and may inform disease prevention strategies in aquaculture. Full article

Mpox virus (MPXV), a member of the Orthopoxvirus genus in the Poxviridae family, has long been endemic in Africa. The interaction between MPXV infection and peripheral immune responses is of great significance. However, the activation of signaling pathways and molecular changes in peripheral blood mononuclear cells (PBMCs) following MPXV infection remain poorly understood. This study evaluated the transcriptomic profiles of rabbit PBMCs during the mpox acute and recovery phases. The results showed that MPXV infection significantly altered the transcriptomic profiles of PBMCs. At 6 days post-infection, pathways related to pathogenic infection and IL-1 response were enriched, while at 14 days post-infection, the T cell receptor signaling pathway was enriched. During the mpox acute phase, inflammatory cytokines in serum such as IL-1α, IL-1β, IL-8, and IL-21 were upregulated, while MMP-9 and NCAM-1 were downregulated. In rabbits and rhesus monkeys, key genes upregulated in common during the mpox acute period were associated with the interferon pathway (e.g., the ISG15, OAS, and IFIT families), while downregulated genes were related to B-cell activation and differentiation (e.g., the MS4A1 and FCRL families). Additionally, rabbits developed protective immunity against reinfection, with neutralizing antibodies effectively activated. These findings provide insights into the molecular characteristics of PBMCs changes in in vivo models of MPXV infection, and offer references for the diagnosis, vaccine development, and therapeutic research of mpox. Full article

Amyotrophic lateral sclerosis (ALS) is a terminal neurodegenerative disease, marked by considerable clinical and molecular heterogeneity. While several genetic drivers have been linked to familial ALS (fALS), the biology of sporadic ALS (sALS)—which accounts for the majority of ALS cases—remains poorly defined. To address this gap, we analyzed 247 bulk mRNA-sequenced post-mortem tissue samples from the lumbar spinal cord and motor cortex and compared expression profiles between fALS, sALS, and controls. Variance-stabilized DEGs from DESeq2 analysis were used as inputs for weighted gene co-expression network analysis (WGCNA). Finally, gene ontology was used to identify transcriptomic signatures and biological pathways unique to sALS and fALS. In the spinal cord, sALS samples exhibited specific downregulation of mitochondrial complex I subunits (e.g., NDUFS8 and NDUFB7) and regulatory genes (e.g., AURKAIP1 and ATP5F1D), suggesting compromised metabolic resilience. In the motor cortex, a co-expression module associated with adaptive immune function and leukocyte infiltration was downregulated in sALS yet upregulated in fALS, indicating distinct inflammatory pathways between these two forms of ALS. Together, our findings highlight that while sALS and fALS are largely the same disease, they exhibit distinct transcriptomic signatures. By accounting for mode of inheritance in study designs—particularly sALS, which represents ~90% of ALS cases—researchers may reveal deeper insights into ALS pathology. This perspective could enable more targeted therapeutic strategies, ultimately improving outcomes for all ALS patients. Full article

Salinity is a pivotal environmental factor that governs crustacean survival and development through its regulatory effects on key physiological processes, including osmoregulation and metabolic homeostasis. In the mud crab Scylla paramamosain, salinity tolerance of the megalopa plays an important role in larval survival rates and aquaculture yield. Here, we employed a combined transcriptomic and proteomic strategy to comprehensively dissect the molecular adaptive mechanisms of S. paramamosain megalopa exposed to acute and prolonged low-salinity stress (8‰) compared to control condition (17‰). Illumina-based transcriptome sequencing generated 81.71 Gb of high-quality clean data, which were assembled into 42,210 unigenes. LC-MS/MS-based proteomic profiling identified 51,390 unique peptides, corresponding to 5909 confidently quantified proteins. Transcriptomic profiling identified 2627 differentially expressed genes (DEGs) under acute low-salinity stress, comprising 1332 upregulated and 1295 downregulated genes compared to the control group. In contrast, a total of 733 DEGs were identified under prolonged low-salinity exposure, including 390 upregulated and 343 downregulated genes. Parallel proteomic analysis identified 199 differentially expressed proteins (DEPs) in the acute stress group, with 105 upregulated and 94 downregulated relative to the control group. Under prolonged stress, 206 DEPs were detected, including 124 upregulated and 82 downregulated proteins compared to the control group. Significant GO term and KEGG pathway enrichments contained metal ion binding, oxidoreductase activity, nucleus, apoptotic process, innate immune response, and amino acid metabolism, suggesting that megalopa employ coordinated regulatory mechanisms involving metabolic reprogramming, immunity system modulation, ion homeostasis maintenance and cell cycle regulation to adapt to hypoosmotic stress. Integrated multi-omics analysis identified 17 genes displaying significant concordant differential expression at both mRNA and protein levels during acute hypoosmotic stress, versus only 5 gene-protein pairs during prolonged stress exposure, indicating extensive post-transcriptional regulation and protein turnover mechanisms in sustained hypoosmotic condition. To the best of our knowledge, this study established the first integrative transcriptome-proteome framework elucidating hypoosmotic adaptation (8‰) mechanisms in S. paramamosain megalopa. The identified molecular signatures offer actionable targets for selective breeding of salinity-tolerant strains and precision management of megalopa culture under suboptimal salinity condition, while fundamentally advancing our mechanistic understanding of osmoregulatory plasticity across decapod crustaceans. Full article

Background/Objectives: Carotenoids in citrus are vital nutritional compounds and precursors of the stress hormone abscisic acid (ABA). SNF1-related kinases (SnRKs)—key regulators of plant stress signaling that phosphorylate is targeting proteins for post-transcriptional regulation—mediate ABA signaling through its subfamily SnRK2-phosphatase type-2C (PP2C)-PYR1-LIKE (PYL) cascades. This study aims to identify the SnRK-PP2C-PYL family members and decipher their underlying post-transcriptional regulatory mechanisms which control carotenoid metabolism in Citrus sinensis for improved nutrition and stress resilience. Methods: SnRK, PP2C, and PYL were identified by integrated HMMER-blastp-CDD pipeline in the Citrus genome. Using two carotenoid-divergent cultivars, ‘Newhall’ (yellow) and ‘Cara Cara’ (red, hyperaccumulating linear carotenoids), we conducted spatiotemporal expression profiling and integrated transcriptomic and metabolomic data via Weighted Gene Co-expression Network Analysis (WGCNA) to identify modules correlated with accumulation. Results: We identified 26 CsSnRKs (1 SnRK1, 7 SnRK2, 18 SnRK3), 57 CsPP2Cs, and 7 CsPYLs in Citrus sinensis. Despite a >26-fold difference in linear carotenoids, structural gene expression was similar among cultivars, strongly implicating post-transcriptional control. WGCNA identified a key turquoise module highly correlated with linear carotenoid content. This module contained phosphorylation-related genes (CsSnRK1/3.5/3.6/3.16, CsPP2C14/15/33/35/38/40/43/56, and CsPYL6), biosynthetic genes (CsPSY1, CsZISO, and CsZDS), and candidate transcription factors. Network analysis predicted that CsSnRKs, CsPP2Cs, and CsPYLs regulate phytoene-derived carotenoid biosynthesis. Conclusions: We propose a novel phosphorylation-mediated post-transcriptional regulatory network in carotenoid accumulation. This mechanism bridges ABA signaling and metabolic adaptation, providing crucial molecular targets for engineering nutrient-dense and climate-resilient citrus varieties. Full article

Background: Effusion-based lymphoma (EBL) is a rare and aggressive large B-cell lymphoma. It presents as a body cavity effusion without a solid mass, lacks HHV-8 association, and typically expresses CD20. Objectives: To better understand the biology of this entity, we performed transcriptomic profiling of eight EBL cases. Methods: We analyzed the cases with the NanoString PanCancer Immune Profiling Panel and compared the results with publicly available datasets representing follicular lymphoma (FL), mantle cell lymphoma (MCL), and large B-cell lymphoma (LBCL) subtypes. Results: Unsupervised clustering and differential expression analysis revealed that EBL cases cluster transcriptionally with the LBCL group. Lymphoma-specific signaling pathway enrichment (SignatureDB) predominantly identified non-germinal center (activated B-cell-type) pathways. In addition, KEGG pathway analyses revealed enrichment in specific inflammatory and immune response pathways that are associated with B-cell lymphoma development in the setting of chronic inflammation, including those linked to Toll-like receptor and NF-κB signaling. Conclusions: These findings support a post-germinal center origin for EBL, which arises in a background of chronic inflammation and persistent antigen stimulation. Full article

Inhalation of multi-walled carbon nanotubes (MWCNTs) poses potential health risks due to their structural similarity to asbestos and their ability to induce chronic lung inflammation, fibrosis, and lung cancer in animal models. This study investigated the pulmonary inflammatory and transcriptomic responses of two distinct MWCNTs—NM-401 (long, rigid) and NM-403 (short, thin)—in rats and mice using intratracheal instillation at matched dose levels at two post-exposure time points. Both MWCNTs induced acute neutrophilic inflammation and dose-dependent transcriptomic alterations in both species, with NM-403 eliciting a stronger response. Transcriptomic profiling revealed a substantial overlap in differentially expressed genes across materials and species, particularly at the early time point. Fibrosis-associated genes were upregulated in both species, with more persistent expression observed in rats. Acute phase response genes, including Orosomucoid 1 and Lipocalin 2 were commonly induced, while Serum Amyloid A3 and Orosomucoid 2 were selectively upregulated in mice. Functional enrichment analyses showed conserved activation of immune and inflammatory pathways. Our findings show that even short, non-fiber-like MWCNTs can provoke potent and persistent pulmonary effects, challenging assumptions based solely on MWCNT properties. Despite differences in long-term responses, the overall inflammatory and transcriptional profiles showed strong interspecies concordance, suggesting that both rats and mice are relevant models for assessing MWCNT-induced pulmonary toxicity. Full article

Background: Self-directed lifestyle modifications are essential for managing symptoms in individuals diagnosed with irritable bowel syndrome (IBS). This study incorporated longitudinal multi-omics profiling to estimate the mechanisms underlying responses to a nurse-led person-centered self-management intervention in young adults with IBS. Methods: This pre-post study was nested within a 12-week parent randomized controlled trial (NCT03332537). Biospecimens (stool and blood) and clinical outcomes were collected at baseline and post-intervention. Symptoms were assessed using the Brief Pain Inventory and PROMIS^® short forms. Host transcriptomic profiling was performed using RNA sequencing, and gut microbial composition was analyzed via 16S rRNA sequencing. Host transcriptomic co-expression and microbial co-abundance modules were identified via weighted gene co-expression network analysis. Associations between multi-omics modules and symptoms were evaluated using linear mixed-effect models. Results: Among the 20 participants, most were non-Hispanic (75%), White (75%), and female (65%). The intervention significantly reduced self-reported pain severity (p = 0.019) and pain interference (p = 0.013). Decreased associations were observed between pain phenotypes and a microbial module enriched in core metabolic pathways (interference: β = −4.7, p < 0.001; severity: β = −2.4, p = 0.02). Anxiety strengthened associations with host transcriptomic cellular energy metabolism pathways post-intervention (p < 0.05). The intervention attenuated associations between fatigue, sleep disturbance, and immune–inflammatory transcriptomic and microbial adaptation modules (p < 0.05). Conclusions: Findings suggest that the IBS self-management intervention induces symptom-specific biological responses, implicating distinct host–microbe pathways. Larger longitudinal studies are warranted to validate these omics-based symptom signatures. Full article

Background/Objectives: The African swine fever virus (ASFV) multi-gene family (MGF) 360 proteins play critical roles in immune evasion, replication regulation, and virulence determination. Despite substantial advances in this field, the functional roles of many members within this gene family remain to be fully characterized. Methods: In this study, Transcriptional kinetics analysis indicated that the expression profile of MGF 360-2L was consistent with that of the late marker gene B646L (p72). Transcriptomic profiling identified 13 and 171 differentially expressed genes (DEGs) at 12 and 24 h post-infection (hpi) with ΔMGF 360-2L, respectively. Results: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that these DEGs were predominantly enriched in Type I interferon (IFN-I) signaling pathways. It is noteworthy that transcriptome analysis further demonstrates that the absence of MGF 360-2L specifically results in the dysregulation of expression of the replication-essential genes E199L and E301R. These findings indicate that MG F360-2L is essential for maintaining the stable expression of these proteins. Conclusions:MGF 360-2L is a late gene that contributes to the precise regulation of viral protein expression and modulates the host immune response during infection. Full article

For 40 years, Intron Retention (IR) was dismissed as splicing noise and is now recognized as a dynamic and evolutionarily conserved mechanism of post-transcriptional gene regulation. Unlike canonical splicing, which excises all introns from pre-mRNAs, IR selectively retains intronic sequences, albeit at seemingly random places; however, current research now reveals that this process is strategic in its retention. IR influences mRNA stability, localization, and translational potential. Retained introns can lead to nonsense-mediated decay, promote nuclear retention, or give rise to novel protein isoforms that contribute to expanding proteomic and transcriptomic profiles. IR is finely regulated by splice site strength, splicing regulatory elements, chromatin structure, methylation patterns, RNA polymerase II elongation rates, and the availability of co-transcriptional splicing factors. IR plays critical roles in cell-type and tissue-specific gene expression with observed patterns, particularly during neuronal, cardiac, hematopoietic, and immune development. It also functions as a molecular switch during cellular responses to environmental and physiological stressors such as hypoxia, heat shock, and infection. Dysregulated IR is increasingly associated with cancer, neurodegeneration, aging, and immune dysfunction, where it may alter protein function, suppress tumor suppressor genes, or generate immunogenic neoepitopes. Experimental and computational tools like RNA-seq, RT-PCR, IRFinder, and IntEREst have enabled transcriptome-wide detection and validation of IR events, uncovering their widespread functional roles. This review will examine current knowledge on the function, regulation, and detection of IR, and also summarize recent advances in understanding its role in both normal and pathophysiological settings. Full article