ObjectiveTo investigate the associations between seminal plasma inflammatory biomarkers, particularly the sTLR4/IL-1β ratio, and sperm chromatin condensation deficiency (SCCD) in men undergoing fertility evaluation, and to assess its potential utility in identifying individuals at risk for SCCD.Methods74 men undergoing fertility evaluation were enrolled and categorized into a Normal SCCD group (SCCD ≤ 30%, n = 37) and an Impaired SCCD group (SCCD > 30%, n = 37) based on aniline blue staining. Seminal plasma levels of inflammatory markers, including HMGB1, sTLR4, IL-1β, TNF-α and oxidative stress markers, including 8-iso-PGF2α, total antioxidant capacity (T-AOC) were measured. Spearman correlation analysis, Firth’s penalized logistic regression, and receiver operating characteristic (ROC) curve analysis was employed to evaluate the discriminative performance of the biomarkers and the combined score, respectively.ResultsUnivariate Firth regression analysis revealed that the sTLR4/IL-1β ratio was a factor associated with reduced risk against SCCD (OR approaching 0, 95% CI: 0.00 - 0.04, P = 0.006), while T-AOC was significantly associated with increased risk of SCCD (OR = 200.99, 95% CI: 1.52 - 38205.02, P = 0.033). Multivariable analysis confirmed that sTLR4/IL-1β remained an independent factor associated with reduced SCCD risk after adjusting for confounders (P < 0.001), whereas T-AOC was not statistically significant in the multivariable model (P = 0.472). ROC curve analysis yielded an area under the curve (AUC) of 0.786 for sTLR4/IL-1β, indicating moderate-to-good discriminative ability.ConclusionA higher seminal plasma sTLR4/IL-1β ratio is independently associated with reduced SCCD risk, suggesting that preserved immunological buffering may protect sperm chromatin integrity. The sTLR4/IL-1β ratio demonstrates moderate-to-good discriminatory ability (AUC = 0.786) and, as an exploratory finding, may serve as a potential auxiliary assessment tool in future larger validation studies.

BACKGROUND:Patients with tumors often develop multiple autoantibodies against tumor-associated antigens. Among these, antinuclear antibodies (ANAs) constitute a clinically important group distributed across the nucleus, cytoplasm, and cytoskeleton. Emerging evidence suggests that ANAs are closely associated with the development and progression of various malignancies, including colorectal cancer (CRC). AIM:To detect ANA fluorescence patterns in CRC using indirect immunofluorescence (IIF) and investigate their correlation with the disease. METHODS:We collected serum samples from patients and healthy controls visiting The Affiliated Panyu Central Hospital of Guangzhou Medical University between May 2023 and March 2024 for analysis. The study included 38 patients with newly diagnosed CRC, 43 patients with colorectal polyps (CRP), and 29 healthy controls. Serum ANA expression was assessed by IIF, and fluorescence patterns were recorded for each group. Differences in ANA titers were compared among each group to analyze the differences in serum ANA-positive expression, which were further analyzed to explore the correlation between ANA expression and CRC screening. RESULTS:ANA positivity rates were 50.00% in the CRC group, 46.51% in the colorectal polyp group, and 6.90% in the healthy control group, with significantly higher rates in the two patient groups compared to the control group (P < 0.05). In the CRC group, the most common fluorescence patterns were nuclear speckled (15.79%) and cytoplasmic speckled (15.79%), with titers predominantly low (1:100, 28.95%). In the colorectal polyp group, nuclear speckled (18.60%) and nuclear homogeneous (11.63%) were the most frequent, with titers also predominantly low (1:100, 37.21%). The distribution of intermediate titers differed significantly among groups (P < 0.05). CONCLUSION:ANAs are associated with both CRP and CRC and may be useful in early CRC screening. Medium-to-high ANA titers, in particular, should prompt further evaluation for possible CRC correlation. Multiple ANA fluorescence patterns can be detected across all groups, with patients with CRP and CRC showing greater pattern diversity than healthy controls.

Post-translational modifications (PTMs) represent a pivotal regulatory mechanism in cellular processes, wherein the addition or removal of specific functional groups to amino acid residues dynamically modulates protein activity, subcellular localization, expression levels, and interactions with other biomolecules. Key PTMs, including phosphorylation, acetylation, methylation, glycosylation, ubiquitination, and emerging types like succinylation and crotonylation, exponentially diversify the proteome’s functional landscape. In lung cancer, PTMs orchestrate critical pathological processes, such as EGFR phosphorylation-driven proliferation, H3K27me3-mediated epigenetic silencing, and KEAP1 succinylation-regulated redox homeostasis. Recent advances in mass spectrometry (MS), phosphoproteomics, and epigenomic profiling have enabled systematic mapping of PTM networks, revealing their potential as diagnostic biomarkers, therapeutic targets, and predictors of drug response. This review synthesizes the mechanistic roles of PTMs in lung cancer pathogenesis and their translational applications, highlighting multi-omics integration and PTM-targeted therapies as future frontiers in precision oncology.

Idiopathic sudden sensorineural hearing loss (ISSNHL) is defined by the rapid onset of hearing impairment without an identifiable etiology. The decreased serum concentrations of 25-hydroxyvitamin D(25(OH)D) was shown to be associated with decreased hearing ability. However, current cross-sectional studies have only demonstrated an association, failing to establish a causal link. Therefore, a comprehensive investigation is necessary to clarify the causal relationship between them. Analysis was done by using largescale genome-wide association analysis(GWAS) summary datasets to give information about the incidence of ISSNHL and genetically predicted serum 25(OH)D levels by a two-sample Mendelian randomization (MR) analysis. Instrumental variables (IVs) were identified as genome-wide significant single-nucleotide polymorphisms (SNPs) with a significance threshold of P < 1 × 10 −8 and an independence criterion of r 2 < 0.001. The GWAS data on serum 25-hydroxyvitamin D levels comprised 6,896,093 SNPs from 496,949 individuals of European ancestry (exposure variable). Outcome data were derived from another GWAS data, including 16,380,424 SNPs from 1,491 European ISSNHL cases and 196,592 controls. MR-Egger, inverse variance weighted (IVW), weighted median, simple mode, and weighted mode, were used to assess causal effects. Heterogeneity tests, horizontal pleiotropy tests, and the leave-one-out method were applied to evaluated the robustness of the MR analysis results. A total of 117 SNPs were employed as instrumental variables ( P < 5 × 10 −8 ). Our results indicated no causal association between serum 25(OH) D levels and the risk of ISSNHL within the European population (IVW; OR = 1.09, 95% CI = 0.81 to 1.48, P = 0.573). Furthermore, the statistical models did not reveal any evidence of heterogeneity or pleiotropy.

The tumor microenvironment (TME) is a complex ecosystem comprising tumor cells and their surrounding components, such as stromal cells, extracellular matrix, blood vessels, and signaling molecules. It functions as the "soil" that sustains tumor survival and progression, critically influencing tumor growth, invasion, metastasis, and drug resistance. As a key component of the TME, the tumor immune microenvironment (TIME) refers specifically to the interactive network between tumor cells and the immune system. This interplay dictates whether tumors are recognized and eliminated by immune surveillance or succeed in evading immune detection.The gastrointestinal microecology (GM) system encompasses the gut microbiota and their respective habitats. Gut microbiota influence tumor progression through immune regulation, metabolic modulation, and genotoxic effects, thereby shaping therapeutic responses. Meanwhile, tumor cells employ diverse metabolic pathways to meet heightened bioenergetic and biosynthetic demands and to mitigate oxidative stress-processes essential for their proliferation and survival. These metabolic adaptations significantly shape TME characteristics, including nutrient availability, hypoxia, and the induction of immunosuppression.This review summarizes the roles of the immune microenvironment, metabolic microenvironment, and gut microbiota in the initiation, progression, and treatment of prostate cancer (PCa). It further illustrates how these three components interact to collectively regulate PCa development and therapeutic outcomes. By integrating recent advances in these areas, we aim to provide new insights into the molecular mechanisms of PCa pathogenesis and to inform comprehensive clinical strategies.

Single-cell transcriptome sequencing technology has been applied to decode the cell types and functional states of immune cells, revealing their tissue-specific gene expression patterns and functions in cancer immunity. Comprehensive assessments of immune cells within and across tissues will provide us with a deeper understanding of the tumor immune system in general. Here, we present Cross-tissue Immune cell type or state Enrichment analysis of gene lists for Cancer (CIEC), the first web-based application that integrates database and enrichment analysis to estimate the cross-tissue immune cell types or states. CIEC version 1.0 consists of 480 samples covering primary tumor, adjacent normal tissue, lymph node, metastasis tissue, and peripheral blood from 323 cancer patients. By applying integrative analysis, we constructed an immune cell type/state map for each context, and adopted our previously developed Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology Based Annotation System (KOBAS) algorithm to estimate the enrichment for context-specific immune cell types/states. In addition, CIEC also provides an easy-to-use online interface for users to comprehensively analyze the immune cell characteristics mapped across multiple tissues, including expression map, correlation, similar gene detection, signature score, and expression comparison. We believe that CIEC will be a valuable resource for exploring the intrinsic characteristics of immune cells in cancer patients and for potentially guiding novel cancer-immune biomarker development and immunotherapy strategies. CIEC is freely accessible at http://ciec.gene.ac/.

Cell death is ubiquitous during development and throughout life and is a genetically determined active and ordered process that plays a crucial role in regulating homeostasis. Cell death includes regulated cell death and non-programmed cell death, and the common types of regulatory cell death are necrosis, apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis. Apoptosis, Necrosis and necroptosis are more common than autophagy, ferroptosis and pyroptosis among cell death. Non-coding RNAs are regulatory RNA molecules that do not encode proteins and include mainly microRNAs, long non-coding RNAs, and circular RNAs. Non-coding RNAs can act as oncogenes and tumor suppressor genes, with significant effects on tumor occurrence and development, and they can also regulate tumor cell autophagy, ferroptosis, and pyroptosis at the transcriptional or post-transcriptional level. This paper reviews the recent research progress on the effects of the non-coding RNAs involved in autophagy, ferroptosis, and pyroptosis on tumorigenesis, tumor development, and treatment, and looks forward to the future direction of this field, which will help to elucidate the molecular mechanisms of tumorigenesis and tumor development, as well as provide a new vision for the treatment of tumors.

Background: Circular RNA (circRNA) is a new type of endogenous single-stranded RNA with a covalently closed circular structure. Increasing evidence shows that circRNA plays an important role in regulating gene expression in tumors. circICMT is a circular RNA produced by the ICMT gene. Currently, the molecular function of circICMT in bladder cancer remains unclear. Method: Differentially expressed circRNAs were identified from RNA sequencing data and circICMT was identified as a new candidate circRNA. qRT-PCR and sanger sequencing were used to detect the expression of circICMT in bladder cancer tissue specimens. Stable cell lines overexpressing and knocking down circICMT were constructed to explore the effect of circICMT on bladder cancer cells. Its biological effects were detected through wound healing experiments, colony formation experiments, CCK-8 experiments and xenogeneic tumorigenesis experiments. Result: This study found that circICMT was significantly upregulated in bladder cancer tissue specimens. Overexpression of circICMT can inhibit cell migration, proliferation and colony formation ability, while knockdown of circICMT promotes the malignant phenotype of bladder cancer cells. Bioinformatics predictions have found that circICMT can bind to a variety of miRNAs and RBPs and may form a complex regulatory network to regulate the progression of bladder cancer. Conclusion: circICMT is significantly highly expressed in bladder cancer, and intervening circICMT expression affects the malignant phenotype of bladder cancer cells in vivo and in vitro, which may provide potential biomarkers and therapeutic targets for the management of bladder cancer.

Background The early diagnosis of systemic lupus erythematosus (SLE) and the assessment of disease activity progression remain a great challenge. Targeted metabolomics has great potential to identify new biomarkers of SLE. Methods Serum from 44 healthy participants and 89 SLE patients were analyzed using HM400 high-throughput targeted metabolomics. Machine learning (ML) with seven learning models and trained the model several times iteratively selected the two best prediction model in a competitive way, which were independent validated by enzyme-linked immunosorbent (ELISA) with 90 SLE patients. Results In this study, 146 differential metabolites, most of them organic acids, amino acids, and bile acids, were detected between patients with initial SLE and healthy participants, and 8 potential biomarkers were found by intersection of ML and statistics (area under the curve [AUC] > 0.95) showing a significant positive correlation with clinical indicators. In addition, we identified and validated 2 potential biomarkers for SLE classification (P < 0.05, AUC > 0.775; N-Methyl-L-glutamic acid, L-2-aminobutyric acid) showing a significant correlation with the SLE Disease Activity Index. These differential metabolites were mainly involved in metabolic pathways, amino acid biosynthesis, 2-oxocarboxylic acid metabolism and other pathways. Conclusion This study indicated that the tricarboxylic acid cycle might be associated with SLE drug therapy. We identified 8 diagnostic models biomarkers and 2 biomarkers that could be used to identify initial SLE and distinguish different activity degree, which will promote the development of new tools for the diagnosis and evaluation of SLE.

Previous studies have shown that phenyllactic acid (alpha-Hydroxyhydrocinnamic acid, 2-Hydroxy-3-phenylpropionic acid, PLA), a type of organic acid metabolite, has excellent diagnostic efficacy when used to differentiate between prostate cancer, benign prostatic hyperplasia, and prostatitis. This research aims to explore the molecular mechanism by which PLA influences the PANoptosis of prostate cancer (PCa) cell lines. First, we found that PLA was detected in all prostate cancer cell lines (PC-3, PC-3M, DU145, LNCAP). Further experiments showed that the addition of PLA to prostate cancer cells could promote ATP generation, enhance cysteine desulfurase (NFS1) expression, and reduce tumor necrosis factor alpha (TNF-α) levels, thereby inhibiting apoptosis in prostate cancer cells. Notably, overexpression of NFS1 can inhibit the binding of TNF-α to serpin mRNA binding protein 1 (SERBP1), suggesting that NFS1 competes with TNF-α for binding to SERBP1. Knockdown of SERBP1 significantly reduced the level of small ubiquity-related modifier (SUMO) modification of TNF-α. This suggests that NFS1 reduces the SUMO modification of TNF-α by competing with SERBP1, thereby reducing the expression and stability of TNF-α and ultimately inhibiting apoptosis in prostate cancer cell lines. In conclusion, PLA inhibits TNF-α induced panapoptosis of prostate cancer cells through metabolic reprogramming, providing a new idea for targeted treatment of prostate cancer.

BACKGROUND Colorectal cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. Syndecan-2 methylation (mSDC2) testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. Cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. AIM To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China. METHODS A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing. Sensitivity and specificity for CRC, advanced adenoma (AA) and advanced colorectal neoplasia (ACN) were determined. High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test. RESULTS A total of 1035 high-risk individuals were included in this study according to established criteria. Among them, 16 suffered from CRC (1.55%), 65 from AA (6.28%) and 189 from non-AAs (18.26%); 150 patients were diagnosed with polyps (14.49%). Diagnoses were established based upon colonoscopic and pathological examinations. Sensitivities of the mSDC2 test for CRC and AA were 87.50% and 40.00%, respectively; specificities were 95.61% for other groups. Positive predictive values of the mSDC2 test for CRC, AA and ACN were 16.09%, 29.89% and 45.98%, respectively; the negative predictive value for CRC was 99.79%. After adjusting for other high-risk covariates, mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN (P < 0.001). CONCLUSION Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

Background: Circulating proteins secreted by tumors are an important source of cancer biomarkers. This study aims to investigate the changes in the content of tumor immune-related circulating proteins in peripheral blood from patients with colorectal cancer (CRC). Methods: Olink's proximity extension assay was used to detect the levels of 92 tumor immune-related circulating proteins in peripheral blood from CRC patients. An enzyme-linked immunosorbent assay was performed to detect the levels of six proteins. Elastic network regression was used to establish the model, and the performance of the model was verified by multiple iterations of cross-validation. Results: The best serum protein signature that was composed of six proteins (IL7, CXCL12, IL10, IL15, CXCL1, and MCP-3) was selected. The area under the curve value of this signature was 0.9924 in the training set and 0.8992 in the total set. IL7 and IL15 levels were significantly higher in the >= 4 cm tumor volume group than in the <4 cm tumor volume group (P = 0.0113 and P = 0.004, respectively). MCP-3 levels were significantly higher in the distant metastasis group than in the non-distant metastasis group (P =0.0465). There was a significant difference in MCP-3 levels among different tumor, node, metastasis stages (P = 0.0496). CXCL1 levels were positively correlated with the absolute count of basophils (R = 0.3220, P = 0.0273), and IL10 levels were positively correlated with the absolute count of neutrophils (R = 0.38737, P = 0.0078). CXCL1, IL7, and IL15 were independent prognostic factors of CRC (hazard ratio [HR] = 0.62, P = 0.006; HR = 0.57, P = 0.006; and HR = 0.64, P = 0.011, respectively). Conclusion: The best serum protein signature model (IL7, CXCL12, IL10, IL15, CXCL1, and MCP-3) was able to distinguish CRC patients from healthy controls. These proteins were also involved in the occurrence and development of CRC.

PurposeSepsis-induced cardiomyopathy (SIC) is a major life-threatening condition in critically infected patients. Early diagnosis and intervention are important to improve patient prognosis. Recognizing the pivotal involvement of the glycolytic pathway in SIC, this study aims to establish a glycolysis-related ceRNA network and explore novel diagnostic avenues.Materials and methodsSIC-related datasets were carefully filtered from the GEO database. CytoHubba was used to identify differentially expressed genes (DEGs) associated with glycolysis. A predictive method was then used to construct an lncRNA-miRNA-mRNA network. Dual-luciferase reporter assays validated gene interactions, and the specificity of this ceRNA network was confirmed in peripheral blood mononuclear cells (PBMCs) from SIC patients. Logistic analysis was used to examine the correlation between the ceRNA network and SIC. Diagnostic potential was assessed using receiver operating characteristic (ROC) curves, and correlation analysis investigated any associations between gene expression and clinical indicators.ResultsIER3 was identified as glycolysis-related DEG in SIC, and a ceRNA network (SNHG17/miR-214-3p/IER3) was established by prediction. Dual luciferase reporter gene assay confirmed the presence of mutual binding between IER3, miR-214-3p and SNHG17. RT-qPCR verified the specific expression of this ceRNA network in SIC patients. Multivariate logistic analysis established the correlation between the ceRNA network and SIC. ROC analysis demonstrated its high diagnostic specificity (AUC > 0.8). Correlation analysis revealed a negative association between IER3 expression and oxygenation index in SIC patients (p < 0.05). Furthermore, miR-214-3p expression showed a negative correlation with NT-proBNP (p < 0.05).ConclusionIn this study, we identified and validated a ceRNA network associated with glycolysis in SIC: SNHG17/miR-214-3p/IER3. This ceRNA network may play a critical role in the onset and development of SIC. This finding is important to further our understanding of the pathophysiological mechanisms underlying SIC and to explore potential diagnostic and therapeutic targets for SIC.

Involving addition of chemical groups or protein units to specific residues of the target protein, post-translational modifications (PTMs) alter the charge, hydrophobicity, and conformation of a protein, which in turn influences protein function, protein-protein interaction, and protein aggregation. These alterations, which include phosphorylation, glycosylation, ubiquitination, methylation, acetylation, lipidation, and lactylation, are significant biological events in the development of cancer, and play vital roles in numerous biological processes. The processes behind essential functions, the screening of clinical illness signs, and the identification of therapeutic targets all depend heavily on further research into the PTMs. This review outlines the influence of several PTM types on prostate cancer (PCa) diagnosis, therapy, and prognosis in an effort to shed fresh light on the molecular causes and progression of the disease.

Purpose: CRC is a malignant tumor seriously threatening human health. Quercetin and kaempferol are representative components of traditional Chinese medicine (TCM). Previous studies have shown that both quercetin and kaempferol have antitumor pharmacological effects, nevertheless, the underlying mechanism of action remains unclear. To explore the synergy and mechanism of quercetin and kaempferol in colorectal cancer. Methods: In this study, network pharmacology, and bioinformatics are used to obtain the intersection of drug targets and disease genes. Training gene sets were acquired from the TCGA database, acquired prognostic-related genes by univariate Cox, multivariate Cox, and Lasso-Cox regression models, and validated in the GEO dataset. We also made predictions of the immune function of the samples and used molecular docking to map a model for binding two components to prognostic genes. Results: Through Lasso-Cox regression analysis, we obtained three models of drug target genes. This model predicts the combined role of quercetin and kaempferol in the treatment and prognosis of CRC. Prognostic genes are correlated with immune checkpoints and immune infiltration and play an adjuvant role in the immunotherapy of CRC. Conclusion: Core genes are regulated by quercetin and kaempferol to improve the patient's immune system and thus assist in the treatment of CRC.

Objectives To identify the most significantly differentially expressed circular RNAs (circRNAs) in colorectal cancer (CRC) tissues in terms of their expression levels and circularity, and to analyze the relationship between their expression levels and the clinical characteristics of patients. Methods circRNA RNA-seq technology was used to screen differentially expressed circRNAs in CRC. Sanger sequencing was used to identify circRNA back-splice junction sites. The relative expression levels of hsa_circ_0003761 (circMSH3) in CRC tissues and cell lines were detected by quantitative real-time fluorescence PCR technology. An RNA-protein pull-down assay was used to detect protein binding to circRNAs. Dual-luciferase reporter gene vectors were constructed to verify that circRNAs bind to microRNAs. Results Four hundred twenty circRNAs were found to be upregulated, and 616 circRNAs were downregulated. circMSH3 was derived from the MutS homolog 3 (MSH3) gene and was formed by a loop of exons 9, 10, 11, and 12. In 110 pairs of CRC and adjacent tissues, circMSH3 expression was 4.487-fold higher in CRC tissues. circMSH3 was also highly expressed in the HT-29 and LOVO CRC cell lines. The expression level of circMSH3 was associated with distant metastasis in CRC patients (P = 0.043); the area under the curve (AUC) of circMSH3 for CRC diagnosis was 0.75, with a sensitivity and specificity of 70.9% and 66.4%, respectively. circMSH3 could bind to a variety of proteins, mainly those involved in RNA transcription, splicing, cell cycle, and cell junctions. Furthermore, circMSH3 could bind to miR-1276, miR-942-5p, and miR-409-3p. Conclusion circMSH3 is a potential biomarker for the diagnosis of CRC and affects the distant metastasis of CRC. Multiple RNA-binding protein binds to circMSH3, and circMSH3 binds to miR-1276, miR-942-5p, and miR-409-3p, thereby affecting the expression of circMSH3.

Objective To determine the effects of circSPECC1 (hsa_circ_0000745) on the proliferation and migration of LNCaP prostate cancer cells and to explore the potential molecular mechanism. Methods Stable circSPECC1 shRNA-expressing and circSPECC1-overexpressing LNCaP cell lines were constructed, and relative gene expression levels were determined by RT-PCR. MTT and clonogenic assays were used to assess proliferative ability while a scratch test was used to analyze cell migration. Western blotting was used to determine protein expression levels. The effects of circSPECC1 on the proliferation of LNCaP prostate cancer cells were observed in vivo. Results circSPECC1 was found to be derived from the SPECC1 (sperm antigen with calponin homology and coiled-coil domains 1) parent gene and to form a loop. Overexpression of circSPECC1 promoted the proliferation and migration of the LNCaP cells, whereas decreased expression of circSPECC1 inhibited these properties. Overexpression of circSPECC1 promoted the expression of MMP-2, MMP-9, VEGF, vimentin, and N-cad but downregulated the expression of E-cad. Decreased expression of circSPECC1 inhibited the expression of MMP-2, MMP-9, VEGF, vimentin, and N-cad but increased the expression of E-cad. Conclusion circSPECC1 promotes cell proliferation and migration by affecting the epithelial-mesenchymal transition of LNCaP prostate cancer cells.

BackgroundNoninvasive methods for the early identify diagnosis of prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa) are current clinical challenges.MethodsThe serum metabolites of 20 healthy individuals and patients with prostatitis, BPH, or PCa were identified using untargeted liquid chromatography-mass spectrometry (LC-MS). In addition, targeted LC-MS was used to verify the organic acid metabolites in the serum of a validation cohort.ResultsOrganic acid metabolites had good sensitivity and specificity in differentiating prostatitis, BPH, and PCa. Three diagnostic models identified patients with PROSTATITIS: phenyllactic acid (area under the curve [AUC]=0.773), pyroglutamic acid (AUC=0.725), and pantothenic acid (AUC=0.721). Three diagnostic models identified BPH: citric acid (AUC=0.859), malic acid (AUC=0.820), and D-glucuronic acid (AUC=0.810). Four diagnostic models identified PCa: 3-hydroxy-3-methylglutaric acid (AUC=0.804), citric acid (AUC=0.918), malic acid (AUC=0.862), and phenyllactic acid (AUC=0.713). Two diagnostic models distinguished BPH from PCa: phenyllactic acid (AUC=0.769) and pyroglutamic acid (AUC=0.761). Three diagnostic models distinguished benign BPH from PROSTATITIS: citric acid (AUC=0.842), ethylmalonic acid (AUC=0.814), and hippuric acid (AUC=0.733). Six diagnostic models distinguished BPH from prostatitis: citric acid (AUC=0.926), pyroglutamic acid (AUC=0.864), phenyllactic acid (AUC=0.850), ethylmalonic acid (AUC=0.843), 3-hydroxy-3-methylglutaric acid (AUC=0.817), and hippuric acid (AUC=0.791). Three diagnostic models distinguished PCa patients with PROSTATITISA < 4.0 ng/mL from those with PSA > 4.0 ng/mL: 5-hydromethyl-2-furoic acid (AUC=0.749), ethylmalonic acid (AUC=0.750), and pyroglutamic acid (AUC=0.929). Conclusions: These results suggest that serum organic acid metabolites can be used as biomarkers to differentiate prostatitis, BPH, and PCa.

目的:分析食物特异性IgG抗体与结直肠癌(CRC)的相关性,计算其与癌胚抗原(CEA)及糖类抗原CA19-9联合检测的诊断效能,初步探讨食物特异性IgG抗体对结直肠癌是否具有预测、诊断价值可能性.方法:选取30例患者进入癌症研究组,41例患者进入息肉炎症组,35例健康体检者进入正常对照组.分析各组别的年龄、性别资料的差异;统计各组别血清中食物特异性IgG抗体的总阳性率的差异;比较各组血清中14项食物特异性IgG抗体水平;对比各组血清的CEA、CA19-9水平;通过受试者工作特征曲线比较单独检测与联合检测之间的潜在诊断性能,以确定其诊断效能.结果:三组的年龄与性别比分别为64.10和19/11、58.0和24/17、58.4和19/16,差异无统计学意义.癌症研究组、息肉炎症组、正常对照组的食物特异性IgG抗体检测的总阳性率分别为63.33％、53.66％、31.43％,差异有统计学意义.进行14项食物特异性IgG抗体水平三组间的差异比较,有差异的过敏原项目为鸡肉、玉米、螃蟹、蘑菇、大米、虾、大豆与西红柿8项(均P＜0.05).三组CEA与CA19-9水平差异均有统计学意义(均P＜0.001).筛选后鸡肉、螃蟹、蘑菇、虾、西红柿这5个过敏原项目与CEA项目、CA19-9项目单独及联合诊断CRC性能比较,七项目联合诊断均大于单独诊断.七项目联合诊断诊断性能较优(AUC=0.925 0,灵敏度=98.68％,特异度=73.33％,Y1=0.720 2).结论:引入食物特异性IgG抗体项目联合CEA、CA19-9能提高CRC的诊断效能的作用.对于食物不耐受人群来讲,避免相应过敏性食物的摄入,有可能会减低患CRC的风险.

Objective The primary objective of this study is to elucidate the molecular mechanism underlying the reversal of peritoneal fibrosis (PF) by Danshenol C, a natural compound derived from the traditional Chinese medicine Salvia miltiorrhiza. By comprehensively investigating the intricate interactions and signaling pathways involved in Danshenol C's therapeutic effects on PF, we aim to unveil novel insights into its pharmacological actions. This investigation holds the potential to revolutionize the clinical application of Salvia miltiorrhiza in traditional Chinese medicine, offering promising new avenues for the treatment of PF and paving the way for evidence-based therapeutic interventions. Methods Firstly, we utilized the YaTCM database to retrieve the structural formula of Danshenol C, while the SwissTargetPrediction platform facilitated the prediction of its potential drug targets. To gain insights into the genetic basis of PF, we acquired the GSE92453 dataset and GPL6480-9577 expression profile from the GEO database, followed by obtaining disease-related genes of PF from major disease databases. R software was then employed to screen for DEG associated with PF. To explore the intricate interactions between Danshenol C's active component targets, we utilized the String database and Cytoscape3.7.2 software to construct a PPI network. Further analysis in Cytoscape3.7.2 enabled the identification of core modules within the PPI network, elucidating key targets and molecular pathways critical to Danshenol C's therapeutic actions. Subsequently, we employed R to perform GO and KEGG pathway enrichment analyses, providing valuable insights into the functional implications and potential biological mechanisms of Danshenol C in the context of PF. To investigate the binding interactions between the core active components and key targets, we conducted docking studies using Chem3D, autoDock1.5.6, SYBYL2.0, and PYMOL2.4 software. We applied in vivo and in vitro experiments to prove that Danshenol C can improve PF. In order to verify the potential gene and molecular mechanism of Danshenol C to reverse PF, we used quantitative PCR, western blot, and apoptosis, ensuring robust and reliable verification of the results. Results ① Wogonin, sitosterol, and Signal Transducer and Activator of Transcription 5 (STAT5) emerged as the most significant constituents among the small-molecule active compounds and gene targets investigated. ②38 targets intersected with the disease, among which MAPK14, CASP3, MAPK8 and STAT3 may be the key targets; The results of GO and KEGG analysis showed that there was a correlation between inflammatory pathway and Apoptosis. ④Real-time PCR showed that the mRNA expressions of MAPK8 (JNK1), MAPK14 (P38) and STAT3 were significantly decreased after Danshenol C treatment ( P < 0.05), while the mRNA expression of CASP3 was significantly increased ( P < 0.05)⑤Western blot showed that protein expressions of CASP3 and MAPK14 were significantly increased ( P < 0.05), while the expression of STAT3 and MAPK8 was decreased after Danshenol C treatment ( P < 0.05). ⑥There was no significant difference in flow analysis of apoptosis among groups. Conclusion The findings suggest that Danshenol C may modulate crucial molecular pathways, including the MAPK, Apoptosis, Calcium signaling, JAK-STAT signaling, and TNF signaling pathways. This regulation is mediated through the modulation of core targets such as STAT3, MAPK14, MAPK8, CASP3, and others. By targeting these key molecular players, Danshenol C exhibits the potential to regulate cellular responses to chemical stress and inflammatory stimuli. The identification of these molecular targets and pathways represents a significant step forward in understanding the molecular basis of Danshenol C's therapeutic effects in PF. This preliminary exploration provides novel avenues for the development of anti-PF treatment strategies and the discovery of potential therapeutic agents. By targeting specific core targets and pathways, Danshenol C opens up new possibilities for the development of more effective and targeted drugs to combat PF. These findings have the potential to transform the landscape of PF treatment and offer valuable insights for future research and drug development endeavors.