Search Results (4,610)

Background: The Space Omics and Medical Atlas (SOMA) is an extensive database containing gene expression information from samples collected during the short-duration Inspiration4 spaceflight mission in 2021. Given our prior understanding of the genetic basis for cardiovascular diseases in spaceflight, including orthostatic intolerance and cardiac deconditioning, we aimed to characterize changes in differential gene expression among astronauts using SOMA-derived data and curated cardiovascular pathways. Methods: Using the KEGG 2021 database, we curated a list of genes related to cardiovascular adaptations in spaceflight, focusing on pathways such as fluid shear stress and atherosclerosis, lipid metabolism, arrhythmogenic ventricular hypertrophy, and cardiac muscle contraction. Genes were cross-matched to spaceflight-relevant datasets from the Open Science Data Repository (OSDR). Differential expression analysis was performed using DESeq2 (v1.40.2, R) with normalization by median-of-ratios, paired pre-/post-flight covariates, and log2 fold change shrinkage using apeglm. Differentially expressed genes (DEGs) were defined as |log2FC| ≥ 1 and FDR < 0.05 (Benjamini–Hochberg correction). Module score analyses were conducted across SOMA cell types to confirm conserved cardiac adaptation genes. Results: A total of 185 spaceflight-relevant genes were analyzed. Statistically significant changes were observed in immune-related cardiovascular pathways, particularly within monocytes and T cells. Persistent upregulation of arrhythmogenic genes such as GJA1 was noted at post-flight day 82. WikiPathways enrichment revealed additional pathways, including focal adhesion, insulin signaling, and heart development. Conclusions: Short-duration spaceflight induces significant gene expression changes that are relevant to cardiovascular disease risk. These changes are mediated largely through immune signaling and transcriptional regulation in peripheral blood mononuclear cells. Findings highlight the need for tailored countermeasures and longitudinal monitoring in future long-duration missions. Full article

Ammonia is a common toxic pollutant in aquaculture environments that poses significant threats to the health, growth, and survival of aquatic organisms. This study investigates the physiological and molecular responses of triploid Crassostrea gigas to ammonia exposure, focusing on the activation and regulation of oxidative stress and immune-related pathways. By integrating histological observations, biochemical assays, and transcriptomic analysis, we systematically revealed the oxidative stress and immune regulatory mechanisms in the hepatopancreas of triploid C. gigas under ammonia exposure. Results showed significant tissue damage in the hepatopancreas, disrupted activities of key antioxidant enzymes including SOD, CAT, and GSH-Px, along with elevated MDA levels, indicating oxidative damage to cellular membrane lipids. Transcriptomic data further indicated significant activation of the glutathione metabolism pathway, with antioxidant genes such as GPX5 and GPX7 displaying a dynamic pattern of initial upregulation followed by downregulation, suggesting their critical roles in modulating oxidative stress responses and maintaining cellular homeostasis. Immunologically, ammonia exposure significantly activated lysosomal and phagosomal pathways, as well as multiple signaling cascades including FOXO, mTOR, and PI3K-Akt. Several key immune regulatory genes exhibited dynamic expression changes, reflecting coordinated regulation of apoptosis, autophagy, and energy metabolism to maintain immune defense and cellular homeostasis. Notably, dynamic expression of the GADD45 gene family in the FOXO signaling pathway underscores the important role of triploid C. gigas in mounting stress responses and adaptive immune regulation under ammonia toxicity. This study provides in-depth molecular insights into the integrated response mechanisms of triploid oysters to ammonia exposure, offering a molecular foundation for understanding bivalve adaptation to ammonia and revealing novel perspectives on molluscan ammonia tolerance. Full article

Interferon regulatory factor 5 (IRF5) plays a pivotal role in innate immune responses and macrophage polarization. Although its role in obesity-associated inflammation has been described, sex-specific differences in adipose IRF5 expression and its association with immune and metabolic markers remain poorly defined. To evaluate sex-specific associations between adipose tissue (AT) IRF5 expression and key inflammatory and metabolic markers in overweight and obese individuals. Subcutaneous AT samples from overweight/obese male and female subjects were analyzed for IRF5 expression using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Correlation and multiple linear regression analyses were performed to identify its associations with inflammatory gene expression and metabolic parameters including insulin, glucose, HOMA-IR, and adipokines. RF5 gene and protein levels were significantly elevated in the AT of overweight/obese females compared to males (p < 0.0001), with expression increasing progressively with BMI in females but not in males. Despite these sex-dependent expression levels, IRF5 demonstrated consistent, sex-independent positive correlations with several core immune and inflammatory markers, including CCR5, CD11c, CD16, CD163, FOXP3, RUNX1, and MyD88. However, distinct sex-specific patterns emerged: in males, IRF5 correlated positively with classical pro-inflammatory markers such as IL-2, IL-6, IL-8, TNF-α, and IRAK1; whereas in females, IRF5 was associated with a broader array of immune markers, including chemokines (CCL7, CXCL11), pattern recognition receptors (TLR2, TLR8, TLR9), and macrophage markers (CD68, CD86), along with anti-inflammatory mediators such as IL-10 and IRF4. Notably, IRF5 expression in overweight/obese males, but not females, was significantly associated with metabolic dysfunction, showing positive correlations with fasting blood glucose, HbA1c, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) levels. Multiple regression analyses revealed sex-specific predictors of IRF5 expression, with metabolic (HOMA-IR) and inflammatory (IRAK1, MyD88) markers emerging in males, while immune-related genes (RUNX1, CD68, CCL7, MyD88) predominated in females. These findings underscore a sex-divergent role of IRF5 in AT, with implications for differential regulation of immune-metabolic pathways in obesity and its complications. Full article

Since 2007, white-nose syndrome (WNS), caused by the fungus Pseudogymnoascus destructans, has killed millions of bats across North America by disrupting hibernation cycles, causing premature fat depletion and starvation. Little brown bats (Myotis lucifugus) from some populations persisting after WNS store larger pre-hibernation fat reserves than bats did before WNS, which may help bats survive winter starvation and mount an immune response to Pd in spring. MicroRNAs (miRNAs) are highly conserved, small, non-coding RNA molecules that regulate gene expression post-transcriptionally. Aberrant miRNA expression can affect metabolic pathways in mammals and has been linked to various diseases. If fat reserves and immune mechanisms influence survival from WNS, then miRNAs regulating metabolic and immune-related genes might affect WNS pathogenesis and bat survival. A previous study identified 43 miRNAs differentially expressed in bats with WNS. We analyzed these miRNAs for their roles in metabolism and immune-related pathways, using DIANA Tools and KEGG analysis, to determine a subset that could serve as biomarkers of pathophysiology or survival in WNS-affected bats. We identified miR-543, miR-27a, miR-92b, and miR-328 as particularly important because they regulate multiple pathways likely important for WNS (i.e., immune response, lipogenesis, insulin signaling, and FOXO signaling). As proof-of-concept, we used reverse transcription quantitative real-time PCR (RT-qPCR) to quantify the prevalence of these miRNAs in plasma samples of bats (n = 11) collected from a post-WNS population during fall fattening. All the selected miRNAs were detectable in at least some bats during fall fattening although prevalence varied among miRNAs. Future in vivo validation studies would help confirm functional roles and biomarker utility of these miRNAs for WNS-affected bats. Full article

Parasitic infections, such as those caused by the myxozoans Myxobolus cerebralis and Tetracapsuloides bryosalmonae, pose major threats to wild and farmed salmonids due to severe tissue damage and impairment of the host immune system. While individual infections have been studied, limited information is available on the host response during co-infection. This study investigated the transcriptomic immune response of rainbow trout (Oncorhynchus mykiss) during single and sequential co-infections with M. cerebralis and T. bryosalmonae using RNA-seq. Trout were exposed to single infections (Mc or Tb) followed by co-infections (Mc⁺ or Tb⁺). Fish were sampled at 31 days post-single infection (1 day post-co-infection). RNA from gill and caudal fin (portal of parasite entry) was sequenced, followed by differentially expressed genes (DEGs) identification and GO and KEGG enrichment. In the caudal fin, Mc⁺ (1 day after co-infection with T. bryosalomne) fish showed mild immune activation with C4B upregulation, while Tb⁺ fish exhibited a stronger response involving IFI44, ISG15, RSAD2, and TLR7 signaling. In gills, Mc⁺ fish showed moderate cytokine-related gene upregulation, while Tb⁺ (1 day after co-infection with M. cerebralis) fish displayed increased expression of humoral response genes (C3, immunoglobulin pathways) but suppression of genes involved in B cell development. These results indicate that the order of infection shapes the outcome of the host immune response, offering candidate targets at the host–pathogen interface. Full article

Lung cancer remains a foremost cause of cancer-related impermanence globally, demanding innovative and effective therapeutic strategies. Polymeric nanoparticles (NPs) have turned up as a promising transport system for drugs due to their biodegradability, biocompatibility, and capability to provide controlled and targeted release of therapeutic agents. This review offers a thorough examination of different polymeric NP platforms, such as chitosan, gelatin, alginate, poly (lactic acid), and polycaprolactone, highlighting their mechanisms, formulations, and applications in the treatment of lung cancer. These NPs facilitate the delivery of chemotherapeutic agents, gene therapies, and immune modulators, with enhanced bioavailability and reduced systemic toxicity. Additionally, advanced formulations such as ligand-conjugated, stimuli-responsive, and multifunctional NPs demonstrate improved tumor-specific accumulation and cellular uptake. The review also discusses quantum dots, magnetic and lipid-based NPs, and green-synthesized metallic polymeric hybrids, emphasizing their potential in theranostics and combination therapies. Preclinical studies show promising results, yet clinical translation faces challenges; for example, large-scale production, long-term toxicity, and regulatory hurdles. Overall, polymeric NPs represent a powerful platform for advancing personalized lung cancer therapy, with future prospects rooted in multifunctional, targeted, and patient-specific nanomedicine. Full article

Psoriasis is a chronic inflammatory skin disease driven by genetic, environmental, and immune factors. While biologics like adalimumab (anti-TNFα) and risankizumab (anti-IL-23) have improved outcomes, patient response variability remains unclear. This study examined immune-related transcriptomic differences between lesional (L) and non-lesional (NL) psoriatic skin, focusing on immune-related hub genes, their plasma levels, and their correlations with severity and treatment response. Patients with moderate-to-severe psoriasis were enrolled before treatment with anti-TNFα (n = 16) or anti-IL-23 (n = 18). Plasma and paired L and NL skin biopsies were collected for RNA sequencing. Gene ontology enrichment analysis found four immune-related terms enriched in L skin: T-helper 17, granulocyte and lymphocyte chemotaxis, and antimicrobial humoral response. A protein–protein interaction network identified ten immune-related hub genes upregulated in L skin that correlated with clinical severity. Patients with prior treatments expressed distinctive gene profiles. Plasma levels of CCL20 strongly correlated with disease severity. Decision tree models identified CCL20 expression in skin and plasma levels of IL-6 and CXCL8 as candidate predictors for anti-TNFα response. Similarly, skin expression of CXCL8, IL-6, and CXCL10, alongside plasma levels of CCL20, IL-6, and CXCL8, may predict anti-IL-23 response. Ten immune-related hubs may serve as possible biomarkers for disease severity and therapeutic response in psoriasis. Full article

Background and Aims: Triple-negative breast cancer (TNBC) is a clinically aggressive malignancy marked by rapid disease progression, limited therapeutic avenues, and high recurrence risk. Ferroptosis an iron-dependent, lipid peroxidation-driven form of regulated cell death that has emerged as a promising therapeutic vulnerability in oncology. This study delineates the ferroptosis-associated molecular architecture of TNBC to identify key regulatory genes with prognostic and translational significance. Methods: Transcriptomic profiles from the GSE103091 dataset (130 TNBC and 30 normal breast tissue samples) were analyzed to identify ferroptosis-related differentially expressed genes (DEGs) using GEO2R. Protein–protein interaction (PPI) networks were constructed via STRING and GeneMANIA, with functional enrichment performed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome analyses. Prognostic relevance was evaluated using GEPIA, BC-GenExMiner, and Kaplan–Meier Plotter survival analyses. Results: Six ferroptosis drivers (MAPK1, TLR4, IFNG, ATM, ULK2, and ATF3) and five suppressors (NFS1, GCLC, TP63, CD44, and SRC) were identified alongside HMOX1, a bifunctional regulator with context-dependent pro- and anti-ferroptotic activity. Enrichment analyses revealed significant associations with oxidative stress regulation, autophagy, immune modulation, and tumor progression pathways. Elevated IFNG expression was consistently linked to improve overall, disease-free, and distant metastasis-free survival, underscoring its dual function in antitumor immunity and ferroptosis sensitization. Conclusions: Ferroptosis represents a critical axis in TNBC pathophysiology, with IFNG emerging as both a prognostic biomarker and a viable therapeutic target. These insights provide a mechanistic foundation for integrating ferroptosis-inducing agents with immunotherapeutic modalities to enhance clinical outcomes and overcome therapeutic resistance in TNBC. Full article

Mannan oligosaccharide (MOS), a prebiotic derived from yeast cell walls, has been shown to enhance growth performance and health status in various aquatic species. As an exogenous antigen adjuvant, MOS modulates T-cell-mediated immune responses, thereby improving immune function and suppressing excessive inflammatory reactions. This study aimed to evaluate the effects of dietary MOS supplementation on growth performance, serum biochemical parameters, muscle composition, digestive enzyme activity, antioxidant and immune status, and the mTOR signaling pathway in juvenile GIFT tilapia (Oreochromis niloticus). Juveniles (initial body weight: 16.17 ± 1.32 g) were randomly assigned to six treatment groups (three replicate tanks per group) and fed diets supplemented with MOS at 0, 0.2%, 0.4%, 0.6%, 0.8%, and 1% (equivalent to 0, 2, 4, 6, 8, and 10 g/kg of diet, respectively) for 60 days. Compared with the control group, fish fed MOS-supplemented diets exhibited significantly higher (p < 0.05) weight gain rates, specific growth rates, and protein efficiency ratios, along with a significantly lower (p < 0.05) feed conversion ratio. Serum albumin, high-density lipoprotein, and lysozyme levels were significantly increased (p < 0.05), whereas triglycerides, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels were significantly decreased (p < 0.05). In the liver, head kidney, and spleen, the expression of pro-inflammatory genes (tumor necrosis factor α, interleukin 1β, interleukin 6, interleukin 8, and interferon γ) was significantly downregulated (p < 0.05), while the expression of antioxidant and protective genes (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, nuclear factor erythroid 2-related factor 2, lysozyme, alkaline phosphatase, interleukin-10, transforming growth factor β, and heat shock protein 70) as well as mTOR signaling pathway-related genes (mammalian target of rapamycin, akt protein kinase B, phosphatidylinositol 3 kinase, and ribosomal protein S6 kinase polypeptide 1) was significantly upregulated (p < 0.05). Overall, MOS positively affects tilapia’s growth, health, and immunity, with 0.60% identified as the optimal dietary level based on growth performance. Full article

Immune checkpoint inhibitors (ICIs) are a key treatment for advanced non-small cell lung cancer (NSCLC), but most patients will ultimately experience disease progression due to acquired resistance to ICI. Clinically, it is relevant to differentiate between systemic progression (SP) and oligoprogression (OP). Following SP, ICI treatment is usually discontinued, while in OP, patients are preferably treated with local ablative treatment with continuation of the ICI treatment. However, with progressive disease, it remains difficult to differentiate between true OP or SP. Circulating tumor DNA (ctDNA) analysis provides an accurate real-time reflection of the tumor burden. It remains elusive if ctDNA abundance and/or dynamics can discriminate between OP and SP. Therefore, the aim of this exploratory cohort study is to evaluate whether the sequential molecular tumor profiling of ctDNA is suitable for discriminating between true OP and SP in advanced NSCLC. Patients with stage III/IV NSCLC showing progression after ≥3 months of ICI were included. OP was defined retrospectively by RECIST response ≥ 6 months after local treatment and continued ICIs. Serial plasma samples were analyzed using the AVENIO ctDNA Expanded NGS assay targeting 77 cancer-related genes. Twenty patients (6 OP, 14 SP) were included. Somatic alterations were detected in 16 patients (median 4 mutations). No significant differences in baseline ctDNA levels, changes at progression, or mutation patterns were observed between OP and SP. Although ctDNA levels generally decreased early after the start of ICI treatment, and were increased at disease progression, mutational profiles of the 77 genes using the AVENIO Expanded ctDNA panel did not distinguish OP from SP. Full article

Goats are important producers of meat, milk, hair, and leather. Early-weaned kids may encounter issues such as weaning stress and stress from high-density farming, which can hinder their growth and development. Therefore, exploring feed additives capable of alleviating stress in kids to enhance their growth performance is of particular importance. This experiment aims to investigate the effects of inulin on the growth performance, immune function, and intestinal health of weaned kids. Thirty healthy 60-day-old Leizhou black goat weaned kids with similar body weights (9.00 ± 0.05 kg) were selected and evenly divided into five groups by weight, with six kids in each group. The control group was fed the basal diet, while the AM HCl group received 0.05‰ aureomycin hydrochloride. The inulin groups were supplemented with 0.1%, 0.3%, and 0.5% inulin, respectively. By comparison, the results of the 0.3% inulin group in this experiment were most consistent with those of the AM HCl group, and the final weight of the kids was the highest. The 0.3% and 0.5% inulin groups had significantly enhanced immune-related indicator (such as sIgA, IgA, and IgG) concentrations and antioxidant activities (p < 0.05) in kids. Inulin significantly increased cecal total volatile fatty acids (TVFA) and the activities of jejunal α-amylase, chymotrypsin, and trypsin (p < 0.05); the activities of intestinal antioxidant enzymes, including GSH-PX, SOD, and T-AOC, were significantly increased (p < 0.05); and the intestinal anti-inflammatory factor IL-10 was significantly elevated (p < 0.05). Inulin significantly increased the mRNA expression levels of the tight junction protein genes TJP1 (ZO-1) and OCLN in the jejunum (p < 0.05). It also significantly upregulated the mRNA expression levels of anti-inflammatory factors TGF-β1 and IL-10 while significantly reducing the mRNA level of pro-inflammatory factor IL-6 in the jejunum (p < 0.05). Therefore, inulin enhanced the growth performance and antioxidant capacity of weaned kids, improved the body’s immune response, and reduced inflammatory responses. Specifically, when comparing the growth status, antioxidant enzyme activity, and tight junction protein mRNA level among the groups of kids, the 0.3% inulin supplementation yielded the best results in this experiment. Full article

Colorectal cancer (CRC) remains a major cause of cancer-related mortality. Cetuximab improves survival by combining EGFR inhibition with immune activation. This study evaluated the influence of killer cell immunoglobulin-like receptor (KIR)-mediated immune responses on cetuximab efficacy in 124 metastatic CRC patients: 55 with wild-type (WT) KRAS and 69 with KRAS mutations. Peripheral blood was genotyped for 19 KIR genes and relevant HLA alleles, focusing on key KIR–HLA interactions (2DL1–C2, 3DL1–Bw4, 3DS1–Bw4). KRAS-WT patients showed better outcomes, receiving more treatment cycles (median: 17 vs. 4) and showing slower disease progression (60% vs. 92.8% at 12 months). WT patients had higher frequencies of inhibitory KIRs and the Bw4 allele, with KIR3DS1–Bw4 heterozygosity linked to longer survival (p = 0.013). In KRAS-mutant patients, heterozygous KIR genotypes (AB) and mixed A/B semi-haplotypes were associated with improved survival (p = 0.002). Multivariate analysis confirmed KIR3DS1–Bw4 as a favorable factor in WT patients and AB genotypes as beneficial in KRAS-mutants. In conclusion, KIR–HLA interactions significantly impact cetuximab efficacy in metastatic CRC, with distinct immunogenetic profiles in WT and KRAS-mutant patients. These results highlight the potential of KIR–HLA profiling to guide personalized treatment strategies. Full article

The pregnane X receptor (PXR), a ligand-activated nuclear receptor, plays a central role in regulating the metabolism of both endogenous substances and xenobiotics. In recent years, increasing evidence has highlighted its involvement in chronic diseases, particularly metabolic disorders and cancer. PXR modulates drug-metabolizing enzymes, transporters, inflammatory factors, lipid metabolism, and immune-related pathways, contributing to the maintenance of hepatic–intestinal barrier homeostasis, energy metabolism, and inflammatory responses. Specifically, in type 2 diabetes mellitus (T2DM), PXR influences disease progression by regulating glucose metabolism and insulin sensitivity. In obesity, it affects adipogenesis and inflammatory processes. In atherosclerosis (AS), PXR exerts protective effects through cholesterol metabolism and anti-inflammatory actions. In metabolic dysfunction-associated steatotic liver disease (MASLD), it is closely associated with lipid synthesis, oxidative stress, and gut microbiota balance. Moreover, PXR plays dual roles in various cancers, including hepatocellular carcinoma, colorectal cancer, and breast cancer. Currently, PXR-targeted strategies, such as small molecule agonists and antagonists, represent promising therapeutic avenues for treating metabolic diseases and cancer. This review comprehensively summarizes the structural features, signaling pathways, and gene regulatory functions of PXR, as well as its role in metabolic diseases and cancer, providing insights into its therapeutic potential and future drug development challenges. Full article

Background/Objectives: Cancer remains a major global health challenge, with RNA modifications increasingly recognized as key regulators of tumor progression. However, integrated pan-cancer analyses across multiple modification types are limited. Methods: We performed a comprehensive analysis of 170 RNA modification-related genes across 33 cancer types, uncovering diverse expression, mutation, and epigenetic patterns. Results: Key regulators such as IGF2BP3, CFI, and ELF3 showed cancer-specific prognostic significance. We developed an RNA Modification Score (RMS) with strong prognostic performance (AUC up to 0.92), correlating with the tumor stage, immune infiltration, and immunotherapy response. High-risk groups exhibited immune checkpoint dysregulation and enriched M1 macrophages in glioblastoma. Drug screening highlighted oncrasin-72 as a potential therapy. Validation via single-cell/spatial transcriptomics and immunohistochemistry confirmed the spatial localization of critical genes like CFI and ELF3. Conclusions: Our study reveals the multifaceted role of RNA modifications in cancer, providing a translational framework for personalized prognosis and therapy in precision oncology. Full article

Background: Pancreatic cancer ranks as the fourth leading cause of cancer-related deaths in the USA. The human aldehyde dehydrogenase (ALDH) family comprises 19 functional members and has been implicated in prognosis and therapy resistance. However, it remains unclear which specific ALDHs are associated with adverse prognoses in pancreatic cancer. Methods: We obtained transcriptomic and clinical data for pancreatic adenocarcinoma (PAAD) from the TCGA, corresponding mutational data, and normal pancreatic tissue transcriptomic data from GTEx. Prognostic analysis was carried out using Kaplan–Meier analysis. KEGG and GO analyses were used for biological signaling pathways, and ESTIMATE algorithms were used for tumor microenvironment (TME) assessment. CIBERSORT algorithm, immune infiltration analysis, and OncoPredict algorithms were employed for predicting chemotherapy sensitivity. Results: Our study identified four of the 19 ALDH genes (ALDH1L1, ALDH3A1, ALDH3B1, ALDH5A1) that were significantly associated with pancreatic cancer prognosis. High expression of ALDH1L1, ALDH3A1, and ALDH3B1 was associated with shorter overall survival, while ALDH5A1 expression was associated with longer overall survival of pancreatic cancer patients. Clinicopathological analysis revealed a significant association with KRAS mutational status and ALDH3A1 expression. Immune correlation analysis indicated that high expression of ALDH3A1 and ALDH3B1 was associated with lower expression of CD8⁺ T cell-associated gene expression. ESTIMATE analyses further revealed that high expression of ALDH3A1 and ALDH3B1 was associated with lower levels of immune cell infiltration. PAAD tumors with low ALDH3A1 expression were more sensitive to paclitaxel. Immunohistochemical analysis demonstrated high expression of ALDH3A1 in pancreatic cancer cells of human tumor tissues compared to normal pancreatic tissues. Conclusions: This study unveils specific ALDH family members relevant for prognosis and chemotherapy response in pancreatic cancer patients. These findings contribute valuable insights into prognostic biomarkers and their potential clinical utility in the treatment of pancreatic adenocarcinoma. Full article