Search Results (127)

Background: Angiosarcomas (ASs) represent a heterogeneous and highly aggressive subset of tumors that respond poorly to systemic treatments and are associated with short progression-free survival (PFS) and overall survival (OS). The aim of this study was to develop and validate an immune-related prognostic model—termed the AS score—using data from two independent sarcoma cohorts. Methods: A prognostic model was developed using a previously characterized cohort of 25 angiosarcoma samples. Candidate genes were identified via the Maxstat algorithm (Maxstat v0.7-25 for R), combined with log-rank testing. The AS score was then computed by weighing normalized gene expression levels according to Cox regression coefficients. For external validation, transcriptomic data from TCGA Sarcoma cohort (n = 253) were analyzed. The Immunoscore—which reflects the tumor immune microenvironment—was inferred using the ESTIMATE package (v1.0.13) in R. All statistical analyses were performed in RStudio (v 4.0.3). Results: Four genes—IGF1R, MAP2K1, SERPINE1, and TCF12—were ultimately selected to construct the prognostic model. The resulting AS score enabled the classification of angiosarcoma cases into two prognostically distinct groups (p = 0.00012). Cases with high AS score values, which included both cutaneous and non-cutaneous forms, exhibited significantly poorer outcomes, whereas cases with low AS scores were predominantly cutaneous. A significant association was observed between the AS score and the Immunoscore (p = 0.025), with higher Immunoscore values found in high-AS score tumors. Validation using TCGA sarcoma cohort confirmed the prognostic value of both the AS score (p = 0.0066) and the Immunoscore (p = 0.0029), with a strong correlation between their continuous values (p = 2.9 × 10⁻⁸). Further survival analysis, integrating categorized scores into four groups, demonstrated robust prognostic significance (p = 0.00021). Notably, in tumors with a low Immunoscore, AS score stratification was not prognostic. In contrast, among cases with a high Immunoscore, the AS score effectively distinguished outcomes (p < 0.0001), identifying a subgroup with poor prognosis but potential sensitivity to immunotherapy. Conclusions: This combined classification using the AS score and Immunoscore has prognostic relevance in sarcoma, suggesting that angiosarcomas with an immunologically active microenvironment (high Immunoscore) and poor prognosis (high AS score) may be prime candidates for immunotherapy and this approach warrants prospective validation. Full article

Background: Hypoxia and immune components significantly shape the tumor microenvironment and influence prognosis and immunotherapy response in gastric cancer (GC). This study aimed to develop hypoxia- and immune-related gene signatures for prognostic evaluation in GC. Methods: Transcriptomic data from TCGA-STAD were integrated with hypoxia- and immune-related genes from InnateDB and MSigDB. A prognostic gene signature was constructed using Cox regression analyses and validated on an independent GSE84437 cohort and single-cell RNA dataset. We further analyzed immune cell infiltration, molecular characteristics of different risk groups, and their association with immunotherapy response. Single-cell RNA-seq data from the TISCH database were used to explore gene expression patterns across cell types. Results: Five genes (TGFB3, INHA, SERPINE1, GPC3, SRPX) were identified. The risk score effectively stratified patients by prognosis, with the high-risk group showing lower overall survival and lower T-cell expression. The gene signature had an association with immune suppression, ARID1A mutation, EMT features, and poorer response to immunotherapy. Gene signature, especially SRPX was enriched in fibroblasts. Conclusions: We developed a robust hypoxia- and immune-related gene signature that predicts prognosis and may help guide immunotherapy strategies for GC patients. Full article

Background: SERPINE1, also known as plasminogen activator inhibitor (PAI), has been proposed as a potential blood biomarker for the early detection and diagnosis of Alzheimer’s disease (AD). Expanding on previous studies, this research contrasted SERPINE1 levels in CSF and brain tissue of AD patients and those at risk for AD with established AD biomarkers. Methods: Utilizing OLINK and immunoassay methods, CSF SERPINE1 protein levels were quantified across two separate cohorts: PREVENT-AD and ADNI. Microarray and RNAseq were used to measure tissue SERPINE1 mRNA levels in two separate cohorts: the Douglas-Bell Canada Brain Bank and the Mayo Clinic Brain Bank. Results: At the pre-clinical stage, elevated CSF levels of pTau, tTau and synaptic markers, alongside reduced hippocampal volume, correlate with CSF SERPINE1 levels. Elevated cortical SERPINE1 mRNA levels in autopsy-confirmed AD show weak correlation with regional plaques and tangles densities, but strong correlation with Braak staging. Conclusions: CSF SERPINE1 levels can be used as an early biomarker for the detection of pathological changes associated with AD. Higher SERPINE1 levels correlate more strongly with tau pathology than with amyloid formation or deposition. Full article

Pear psylla (Cacopsylla chinensis), a major pear tree pest widely distributed in China, is increasingly affecting the productivity of orchards. This species exhibits seasonal polyphenism with two distinct forms, namely, a summer form and a winter form. Through topically applying Beauveria bassiana conidial suspensions to the abdominal cuticle of C. chinensis, we demonstrated that the entomopathogenic fungus B. bassiana exhibits significant yet phenotypically divergent virulence against these two forms. Using PacBio SMRT sequencing and Illumina RNA-seq, we analyzed transcriptomic changes post-infection, revealing form-specific immune responses, with 18,232 and 5027 differentially expressed genes identified in summer- and winter-form pear psylla, respectively, and a total of 3715 DEGs shared between the two seasonal phenotypes. In summer-form individuals, B. bassiana infection disrupted oxidative phosphorylation and downregulated immune recognition genes, cellular immune-related genes, and signaling genes, along with the upregulation of the immune inhibitor serpin, indicating immunosuppression. Conversely, in winter-form individuals, immune-related genes and glycolytic rate-limiting enzymes were upregulated after infection, suggesting that the winter-form immune system normally responds to B. bassiana infection and supports efficient defense through metabolic reprogramming to fuel energy-demanding defenses. These findings advance our understanding of C. chinensis/B. bassiana interactions, providing a basis for elucidating immune regulation in seasonally polymorphic insects. The results also inform strategies to optimize B. bassiana-based biocontrol, contributing to sustainable pear psylla management. Full article

Background/Objectives: Cumulus cells have been proposed to be indicators of oocyte quality. In this study, oocyte cumulus cells were analyzed for SERPINE gene expression. High SERPINE gene expression in cumulus cells is associated with reduced oocyte maturity. However, high mRNA levels in granulosa cells are associated with follicles that result in pregnancy. This study aimed to evaluate SERPINE gene expression in cumulus cells across different ovarian stimulation protocols and its potential impact on follicle number, oocyte maturity, and embryo quality. Methods: The sample of the study consisted of 93 infertile women that underwent a five-day fixed antagonist protocol. Detection of SERPINE gene expression levels in cumulus cells was performed by extracting and isolating the total RNA produced in granulosa cells, and conducting cDNA synthesis and Real-Time Polymerase Chain Reaction. Results: The SERPINE gene expression in CCs was assessed in 71 samples. The SERPINE gene expression levels in CCs were categorized based on the ΔCp values. Most participants (65.9%) exhibited a high expression of the SERPINE gene, with ΔCp values greater than 2. Higher gene expression resulted in a higher number of follicles. However, no statistically significant results were observed regarding the number of follicles and the number of embryos. Conclusions: The study results provide insights into the expression patterns of the SERPINE gene in CCs and underscore the complexity of fertility-related biomarkers and the need for further investigation. SERPINE expression appears to be associated with follicle count, while its role in predicting oocyte quality and pregnancy success remains inconclusive. Full article

Diabetic cardiomyopathy (DCM), a critical complication of type 2 diabetes mellitus (T2DM), is marked by metabolic dysfunction, oxidative stress, and chronic inflammation, ultimately progressing to heart failure. This study investigated the synergistic therapeutic potential of Hippophae rhamnoides L. (sea buckthorn, SBU) extract and metformin in a mouse model of T2DM-induced DCM. T2DM was induced using a 45% high-fat-AGEs-enriched diet, followed by treatment with SBU, metformin, or their combination. Treatment effects were monitored through bioinformatic analysis, chemoinformatic prediction, behavioral testing, biochemical assays, histopathological evaluations and gene expression profiles. Based on bioinformatic analysis, we identified key hub genes involved in the diabetic cardiomyopathy including SERPINE1, NRG1, MYH11, PTH, NR4A2, NRF2, PGC1α, GPX4, ATF1, ASCL2, NOX1, NLRP3, CCK8, COX2, CCL2, PTGS2, EGFR, and oncostatin, which are pivotal in modulating the ferroptosis pathway. Furthermore, the expression of long non-coding RNAs (lncRNAs) NEAT1 and MALAT1, critical regulators of inflammation and cell death, was effectively downregulated, correlating with decreased levels of the pro-inflammatory marker oncostatin. The combined therapy significantly improved glucose regulation, reduced systemic inflammation and protected the heart from oxidative damage. Histopathological analysis revealed notable reductions in cardiac necrosis and fibrosis. Particularly, the combination therapy of SBU and metformin demonstrated a synergistic effect, surpassing the benefits of individual treatments in preventing cardiac damage. These findings highlight the potential of integrating SBU with metformin as a novel therapeutic strategy for managing DCM by targeting both metabolic and ferroptosis-related pathways. This dual intervention opens promising avenues for future clinical applications in diabetic heart disease management, offering a comprehensive approach to mitigating the progression of DCM. Full article

Background/Objectives: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Variants in genes that regulate processes such as apoptosis and angiogenesis play a significant role in CRC. The objective of this study is to investigate the possible association between RASSF1 (rs2073498), SERPINE1 (rs1799889), EFNA1 (rs12904), and RAD51 (rs1801320) variants and clinicopathological characteristics of Mexican patients with CRC. Methods: DNA of peripheral blood samples was obtained from 631 individuals (349 patients and 282 control individuals). The RASSF1 (rs2073498), SERPINE1 (rs1799889), EFNA1 (rs12904), and RAD51 (rs1801320) variants were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The association was calculated using the odds ratio (OR) test. p-values were adjusted by the Bonferroni test (0.0125). In silico analysis programs, including Combined Annotation Dependent Depletion (CADD), Polymorphism Phenotyping-2 (PolyPhen-2), and Gene Expression Profiling Interactive Analysis (GEPIA), were conducted to predict the functional impact of these variants. Results: Patients carrying the G/A genotype of the RASSF1 (rs2073498) variant showed an association with CRC characteristics, including TNM stages and tumor location (OR > 2.5, p = 0.001). Regarding the SERPINE1 (rs1799889) variant, patients carrying the 5G/4G genotype showed an association between TNM stages and tumor location in the rectum (OR > 1.5, p ≤ 0.05). Patients with the G/G genotype for the EFNA1 (rs12904) variant showed an association with TNM stages and rectal tumor location (OR > 2.0, p = 0.001). The RAD51 (rs1801320) variant had no association with colorectal cancer. Conclusions: RASSF1 (rs2073498), SERPINE1 (rs1799889), and EFNA1 (rs12904) variants significantly influence colorectal cancer risk. Full article

Anthrax represents a disease resulting from infection by toxin-secreting bacteria, Bacillus anthracis. This research aimed to identify new therapeutic targets to combat anthrax. We performed assays to assess cell viability, apoptosis, glycogen consumption, and compound uptake and release in hepatocytes and cardiomyocytes responding to anthrax toxins. Microarray analysis was carried out to identify the genes potentially involved in toxin-induced toxicity. Knockdown experiments were performed to validate the contributions of the identified genes. Our study showed that anthrax edema toxin (EdTx) and lethal toxin (LeTx) induced lethal damage in mouse liver and heart, respectively. Microarray assays showed that 218 genes were potentially involved in EdTx-mediated toxicity, and 18 genes were potentially associated with LeTx-mediated toxicity. Among these genes, the knockdown of Rgs1, Hcar2, Fosl2, Hcar2, Cxcl2, and Cxcl3 protected primary hepatocytes from EdTx-induced cytotoxicity. Plasminogen activator inhibitor 1 (PAI-1)-encoding Serpine1 constituted the most significantly upregulated gene in response to LeTx treatment in mouse liver. PAI-1 knockout mouse models had a higher tolerance to LeTx compared with wild-type counterparts, suggesting that PAI-1 is essential for LeTx-induced toxicity and might represent a therapeutic target in LeTx-induced tissue damage. These results provide potential therapeutic targets for combating anthrax-toxin-induced liver and heart damage. Full article

Schizophrenia (SZ) is a chronic disabling mental disorder with high heritability, and several immune-regulating genes have been implicated in its pathophysiology In this study, we investigated the expression of Toll-like receptors (TLRs) 1, 2, and 6 in peripheral blood monocytes from SZ patients and healthy control subjects (HCSs) in the Mexican population, focusing on specific SZ-associated gene variants. Gene expressions were assessed by qPCR, and protein expression was measured using flow cytometry. The secretory profiles of MALP2-stimulated monocytes were evaluated through immunoproteomic arrays. Our results indicate that patients with SZ carrying the rs4833093/TLR1 GG genotype exhibited significantly lower TLR1 gene expression compared to TT carriers. Notably, HCSs with the TT genotype showed markedly higher TLR1 protein expression, while all patients with SZ exhibited significantly reduced protein levels regardless of genotype. Furthermore, monocytes from patients with SZ displayed altered secretion profiles upon TLR stimulation, with significant elevations in IL-18, uPAR, angiopoietin-2, and serpin E1, alongside reductions in MCP-1, IL-17A, IL-24, MIF, and myeloperoxidase compared to HCSs. These findings suggest a dysfunctional TLR-mediated innate immune response in SZ. Full article

Endocrine-disrupting chemicals (EDCs) significantly damage biological systems related to reproductive, neurological, and metabolic functions. Approximately 1000 chemicals are known to possess endocrine-acting properties, including bisphenol A (BPA) and di(2-ethylhexyl) phthalate (DEHP). This study primarily focuses on the potential effects of EDCs on the transcriptional levels of innate immune prophenoloxidase (proPO) system-related genes under oxidative stress in the gonads and stomach of the mud crab Macrophthalmus japonicus, an indicator species for assessing coastal benthic environments, when exposed to 1 µg L⁻¹, 10 µg L⁻¹, and 30 µg L⁻¹ BPA or DEHP. After EDC exposure, the expression of lipopolysaccharide and β-1,3-glucan-binding protein (LGBP), a pattern recognition protein that activates the proPO system, was upregulated in the stomach of M. japonicus, whereas LGBP gene expression was downregulated in the gonads. In the gonads, which is a reproductive organ, EDC exposure mainly induced the transcriptional upregulation of trypsin-like serine protease (Tryp) at relatively low concentrations. In the stomach, which is a digestive organ, LGBP expression was upregulated at relatively low concentrations of EDCs over 7 days, whereas all proPO system-related genes (LGBP, Tryp, serine protease inhibitor (Serpin), and peroxinectin (PE)) responded to all concentrations of EDCs. These results suggest that the antioxidant and immune defense responses of the proPO system to EDC toxicity may vary, causing different degrees of damage depending on the tissue type in the mud crab. Full article

Rice planthoppers, including Nilaparvata lugens, Sogatella furcifera, and Laodelphax striatellus, are major agricultural pests. Serpins, which function as serine protease inhibitors, play a pivotal role in the immune systems of these insects, especially within the Toll signaling pathway and the prophenoloxidase (PPO) cascade. This study presents a comparative analysis of serpin genes among these species, highlighting their roles in immunity and development. Utilizing genomic and bioinformatics approaches, we identified 11, 11, and 14 serpin genes in N. lugens, S. furcifera, and L. striatellus, respectively. Phylogenetic analysis revealed a close evolutionary relationship between these serpin genes and Bombyx mori BmSerpins, emphasizing the functional diversity of the serpin family. Structural analysis confirmed the presence of the reactive center loop (RCL) in all serpin proteins, with the Serpin7 subfamily showing a unique dual RCL configuration. Expression profiling showed species-specific serpin expression patterns across different life stages and adult tissues. Moreover, transcriptional analysis of serpin genes in the three planthoppers following Metarhizium infection uncovered distinct immune regulatory patterns two days post-infection. Notably, the expression of NlSerpin2-2/6, SfSerpin4/6/7-1, and LsSerpin4/5-2/6 was upregulated post-infection, potentially enhancing antifungal capabilities. In contrast, the expressions of NlSerpin1/7-1/9 and LsSerpin1/2/3/8/13 were downregulated, possibly suppressing immune responses. Moreover, Serpin6s, which share a conserved phylogenetic lineage, exhibited enhanced immune activity in response to fungal invasion. These insights into serpin-mediated immune regulation could contribute to the development of novel pest-control strategies. Full article

This paper presents a comprehensive comparative analysis of biomarkers for head and neck cancer (HNC), a prevalent but molecularly diverse malignancy. We detail the roles of key proteins and genes in tumourigenesis and progression, emphasizing their diagnostic, prognostic, and therapeutic relevance. Our bioinformatic validation reveals crucial genes such as AURKA, HMGA2, MMP1, PLAU, and SERPINE1, along with microRNAs (miRNA), linked to HNC progression. OncomiRs, including hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-196a-5p, and hsa-miR-200c-3p, drive tumourigenesis, while tumour-suppressive miRNAs like hsa-miR-375 and hsa-miR-145-5p inhibit it. Notably, hsa-miR-155-3p correlates with survival outcomes in addition to the genes RAI14, S1PR5, OSBPL10, and METTL6, highlighting its prognostic potential. Future directions should focus on leveraging precision medicine, novel therapeutics, and AI integration to advance personalized treatment strategies to optimize patient outcomes in HNC care. Full article

High salt (HS) consumption is an independent risk factor for neurodegenerative diseases such as dementia, stroke, and cerebral small vessel disease related to cognitive decline. Recently, Alzheimer’s disease-like pathology changes have been reported as consequences of a HS diet in wild-type (wt) mice. However, it has not been revealed how HS diets accelerate the progress of Alzheimer’s disease (AD) in APP/PS1 mice. Here, we fed APP/PS1 mice a HS diet or normal diet (ND) for six months; the effects of the HS/ND on wt mice were also observed. The results of our behavior test reveal that the HS diet exacerbates anxiety, β-amyloid overload, neuron loss, and synapse damage in the hippocampi of APP/PS1 mice; this was not observed in HS-treated wt mice. RNA sequencing shows that nearly all serpin family members were increased in the hippocampus of HS-treated APP/PS1 mice. Gene function analysis showed that a HS diet induces neurodegeneration, including axon dysfunction and neuro-ligand-based dysfunction, and regulates serine protein inhibitor activities. The mRNA and protein levels of Serpina3n were dramatically increased. Upregulated Serpina3n may be the key for β-amyloid aggregation and neuronal loss in the hippocampus of HS-treated APP/PS1 mice. Serpina3n inhibition attenuated the anxiety and increased the number of neurons in the hippocampal CA1(cornu ammonis) region of APP/PS1 mice. Our study provides novel insights into the mechanisms by which excessive HS diet deteriorates anxiety in AD mice. Therefore, decreasing daily dietary salt consumption constitutes a pivotal public health intervention for mitigating the progression of neuropathology, especially for old patients and those with neurodegenerative disease. Full article

Diabetic kidney disease (DKD) is a serious microvascular complication of type 2 diabetes mellitus (T2DM). Despite the numerous genetic loci that have been associated with the disease in T2DM, the genetic architecture of DKD remains unclear until today. In contrast to SERPINE1, the contribution of SERPINB2 has not been examined in DKD. Therefore, we conducted the first genetic association study of SERPINB2 to elucidate its role in DKD. In total, the study involved 197 patients with DKD, 155 patients with T2DM without microvascular complications (diabetic kidney disease, diabetic retinopathy, and diabetic neuropathy), and 246 healthy controls. The generalized odds ratio (OR_G) was calculated to estimate the risk on DKD development. The present association study regarding SERPINB2 SNPs (rs4941230, rs3819335, rs13381217, rs6140) did not reveal any significant association between SERPINB2 variants and DKD. Additional studies in other populations are necessary to further investigate the role of this gene in the progression of diabetes mellitus and development of DKD. Full article

Pharmacogenomic analysis based on drug transcriptome characteristics is widely used to identify mechanisms of action. The purpose of this study was to elucidate the molecular mechanism of protective effect against adriamycin (ADM)-induced mpc5 cell injury of Chinese cordyceps aqueous extracts (WCCs) by a systematic transcriptomic analysis. The phytochemicals of WCCs were analyzed via the “phenol–sulfuric acid method”, high-performance liquid chromatography (HPLC), and HPLC–mass spectrometry (MS). We analyzed the drug-reaction transcriptome profiles of mpc5 cell after treating them with WCCs. RNA-seq analysis revealed that WCCs alleviated ADM-induced mpc5 cell injury via restoring the expression of certain genes to normal level mainly in the one-carbon pool by the folate pathway, followed by the relaxin, apelin, PI3K-Akt, and nucleotide-binding, oligomerization domain (NOD)-like receptor signaling pathway, enhancing DNA synthesis and repair, cell proliferation, fibrosis reduction, and immune regulation. Otherwise, WCCs also modulated the proliferation and survival of the mpc5 cell by regulating metabolic pathways, and partially restores the expression of genes related to human disease pathways. These findings provide an innovative understanding of the molecular mechanism of the protective effect of WCCs on ADM-induced mpc5 cell injury at the molecular transcription level, and Mthfd2, Dhfr, Atf4, Creb5, Apln, and Serpine1, etc., may be potential novel targets for treating nephrotic syndrome. Full article