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Sepsis-associated acute kidney injury (S-AKI) is a common disease in pediatric intensive care units (ICU) with high morbidity and mortality. The newly discovered results indicate that microRNAs (miRNAs) play an important role in the diagnosis and treatment of S-AKI and can be used as markers for early diagnosis. In this study, the expression level of miR-16-5p was found to be significantly upregulated about 20-fold in S-AKI patients, and it also increased by 1.9 times in the renal tissue of S-AKI mice. Receiver operating characteristic (ROC) curve analysis showed that miR-16-5p had the highest predictive accuracy in the diagnosis of S-AKI (AUC = 0.9188). In vitro, the expression level of miR-16-5p in HK-2 cells treated with 10 μg/mL lipopolysaccharide (LPS) increased by more than 2 times. In addition, LPS-exposed renal tissue and HK-2 cells lead to upregulation of inflammatory cytokines IL-6, IL-1β, TNF-a, and kidney damage molecules kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL). However, inhibition of miR-16-5p significantly mitigated LPS expose-mediated kidney injury and inflammation. Furthermore, LPS-exposed HK-2 cells increased more than 1.7-fold the expression levels of Bax and caspase-3, decreased 3.2-fold the expression level of B-cell lymphoma-2 (Bcl-2), and significantly promoted the occurrence of apoptosis. MiR-16-5p mimic further increased LPS-induced apoptosis in HK-2 cells. Nevertheless, inhibition of miR-16-5p significantly attenuated this effect. In summary, up-regulation of miR-16-5p expression can significantly aggravate renal injury and apoptosis in S-AKI, which also proves that miR-16-5p can be used as a potential biomarker to promote early identification of S-AKI. [ABSTRACT FROM AUTHOR]

Abstract Epithelial splicing regulatory protein 2 (ESRP2),an important alternative splicing protein of mRNA, is reported to have a dual role in tumors, which can promote or inhibit the occurrence and development of tumors. However, the function and mechanism of ESRP2 in breast cancer (BC) remain unclear. The distribution of ESRP2 expression in breast cancer and the correlation between ESRP2 expression and the overall survival rate were detected by The Cancer Genome Atlas (TCGA) database. Gene Ontology(GO)analysis, containing biological process, cellular components, and molecular function, was utilized to evaluate the potential mechanism of ESRP2 in breast cancer. The ESRP2 expression in breast cancer cell lines was detected by real-time quantitative PCR analysis (RT-qPCR) and western blotting. Cell clone was performed to examine the proliferation of ESRP2 knockdown in MCF-7 cells. The cell cycle was measured by flow cytometry assays. The role of ESRP2 knockdown in synergistic effect with chemotherapeutic agents was also determined by MTT assay. Bioinformatics analysis demonstrated that the ESRP2 gene was elevated in breast cancer cells and its overexpression was strongly correlated with shorter overall survival. GO analysis revealed that ESRP2 expression was related to cell proliferation. ESRP2 mRNA and protein expression were elevated in breast cancer cell lines, compared to the normal human breast cell line MCF-10 A. Dwon-regulation of ESRP2 inhibited cell proliferation and promoted the sensitivity of chemotherapy drug, Cisplatin(DDP) and Paclitaxel (TAXOL), in MCF-7 cells.Additionally, ESRP2 knockdown obstructed the cell cycle at the G1 phase and caused a decrease in cyclinD1 protein expression. These findings reveal that ESRP2 is highly expressed in breast cancer and is correlated with poor prognosis in breast cancer patients. ESRP2 knockdown can inhibit MCF-7 cell proliferation by arresting the cell cycle at the G1 phase and promoting the sensitivity of chemotherapy drugs (DDP and TAXOL)in MCF-7 cells. ESRP2 may be required for the regulation of breast cancer progression, as well as a critical target for the clinical treatment of breast cancer.

Abstract Background We aimed to determine the potential predictive value of the intra-tumoral microbiome as a marker of the response to external beam radiation therapy (EBRT) in cervical cancer (CC). Methods A prospective longitudinal trial of 36 CC patients receiving pelvic radiotherapy was designed to investigate microbial characteristic signatures and diversity (alpha and beta) of multiple sites (tumor, vaginal, gut, urethral, and oral) in the superior response (SR) and inferior response (IR) groups of CC patients by 16S rRNA sequencing. Utilized the least absolute shrinkage and selection operator (LASSO) logistic regression method to analyze clinicopathological factors that potentially influenced the efficacy of EBRT. LEfSe analysis highlighted the microbiome features that best distinguished the categorized patient samples. Selected parameters were validated with Spearman correlation analysis, receiver operating characteristic (ROC) area under the curve (AUC) analysis and Kaplan-Meier survival analysis. Results Firstly, in our cohort, LASSO logistic regression analysis revealed no association between clinicopathological factors and EBRT efficacy. Subsequently, we employed 16S rRNA sequencing to compare microbiome differences across multiple sites and their correlations with major clinicopathological factors. We discovered that the intra-tumoral microbiome was independent of clinicopathologic features and represented the most direct and reliable reflection of the microbial differences between the SR and IR groups. We found lower alpha diversity in the tumor microbiome of SR group and identified the most relevant microbiome taxa (Bifidobacteriaceae, Beijerinckiaceae, and Orbaceae) associated with the efficacy of the response to EBRT in CC patients. We then conducted ROC analysis, finding that specific microbial taxa had an AUC of 0.831 (95% CI, 0.667–0.995), indicating the potential of these taxa as biomarkers for predicting EBRT efficacy. Kaplan-Meier survival analysis showed a better prognosis for patients with lower alpha diversity and higher relative abundance of Bifidobacteriaceae. Conclusions Our data suggested that intra-tumoral specific microbiome taxa and lower alpha diversity may play an important role in the CC patient sensitivity to EBRT and offer novel potential biomarkers for predicting the response to EBRT efficacy.

Multiple sclerosis (MS) is an autoimmune disorder caused by chronic inflammatory reactions in the central nervous system. Currently, little is known about the changes of plasma proteomic profiles in Chinese patients with MS (CpwMS) and its relationship with the altered profiles of multi-omics such as metabolomics and gut microbiome, as well as potential molecular networks that underlie the etiology of MS. To uncover the characteristics of proteomics landscape and potential multi-omics interaction networks in CpwMS, Plasma samples were collected from 22 CpwMS and 22 healthy controls (HCs) and analyzed using a Tandem Mass Tag (TMT)-based quantitative proteomics approach. Our results showed that the plasma proteomics pattern was significantly different in CpwMS compared to HCs. A total of 90 differentially expressed proteins (DEPs), such as LAMP1 and FCG2A, were identified in CpwMS plasma comparing to HCs. Furthermore, we also observed extensive and significant correlations between the altered proteomic profiles and the changes of metabolome, gut microbiome, as well as altered immunoinflammatory responses in MS-affected patients. For instance, the level of LAMP1 and ERN1 were significantly and positively correlated with the concentrations of metabolite L-glutamic acid and pro-inflammatory factor IL-17 (Padj < 0.05). However, they were negatively correlated with the amounts of other metabolites such as L-tyrosine and sphingosine 1-phosphate, as well as the concentrations of IL-8 and MIP-1α. This study outlined the underlying multi-omics integrated mechanisms that might regulate peripheral immunoinflammatory responses and MS progression. These findings are potentially helpful for developing new assisting diagnostic biomarker and therapeutic strategies for MS. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine the potential predictive value of the intra-tumoral microbiome as a marker of the response to external beam radiation therapy (EBRT) in cervical cancer (CC). Methods: A prospective longitudinal trial of 36 CC patients receiving pelvic radiotherapy was designed to investigate microbial characteristic signatures and diversity (alpha and beta) of multiple sites (tumor, vaginal, gut, urethral, and oral) in the superior response (SR) and inferior response (IR) groups of CC patients by 16S rRNA sequencing. Utilized the least absolute shrinkage and selection operator (LASSO) logistic regression method to analyze clinicopathological factors that potentially influenced the efficacy of EBRT. LEfSe analysis highlighted the microbiome features that best distinguished the categorized patient samples. Selected parameters were validated with Spearman correlation analysis, receiver operating characteristic (ROC) area under the curve (AUC) analysis and Kaplan-Meier survival analysis. Results: Firstly, in our cohort, LASSO logistic regression analysis revealed no association between clinicopathological factors and EBRT efficacy. Subsequently, we employed 16S rRNA sequencing to compare microbiome differences across multiple sites and their correlations with major clinicopathological factors. We discovered that the intra-tumoral microbiome was independent of clinicopathologic features and represented the most direct and reliable reflection of the microbial differences between the SR and IR groups. We found lower alpha diversity in the tumor microbiome of SR group and identified the most relevant microbiome taxa (Bifidobacteriaceae, Beijerinckiaceae, and Orbaceae) associated with the efficacy of the response to EBRT in CC patients. We then conducted ROC analysis, finding that specific microbial taxa had an AUC of 0.831 (95% CI, 0.667–0.995), indicating the potential of these taxa as biomarkers for predicting EBRT efficacy. Kaplan-Meier survival analysis showed a better prognosis for patients with lower alpha diversity and higher relative abundance of Bifidobacteriaceae. Conclusions: Our data suggested that intra-tumoral specific microbiome taxa and lower alpha diversity may play an important role in the CC patient sensitivity to EBRT and offer novel potential biomarkers for predicting the response to EBRT efficacy. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) scans and magnetic resonance imaging (MRI) are commonly utilized to detect brain gliomas and central nervous system inflammation diseases. However, there are instances where depending solely on medical imaging for a precise diagnosis may result in unsuitable medications or treatments. Pathological analysis is regarded as the definitive method for diagnosing brain gliomas or central nervous system inflammation diseases. To achieve this, a craniotomy or stereotaxic biopsy is necessary to collect brain tissue, which can lead to complications such as cerebral hemorrhage, neurological deficits, cerebrospinal fluid leaks, and cerebral edema. Consequently, the advancement of non-invasive or minimally invasive diagnostic techniques is currently a high priority. This study included samples from four glioma patients and five patients with central nervous system inflammatory diseases, comprising both serum and paired cerebrospinal fluid (CSF). A total of 40 human cytokines were identified in these samples. We utilized a receiver operating characteristic (ROC) analysis to assess the sensitivity and specificity for distinguishing central nervous system inflammation diseases and gliomas. Additionally, we examined the correlation of these factors between serum and CSF in the patients. Ultimately, the identified factors were validated using serum from patients with clinically confirmed gliomas and central nervous system inflammation diseases followed by detection and statistical analysis through ELISA. The levels of serum factors IL-4, IFN-α, IFN-γ, IL-6, TNF-α, CCL4, CCL11, and VEGF were found to be significantly higher in gliomas compared with inflammatory diseases of the central nervous system (p < 0.05). Furthermore, a strong correlation was observed between the levels of CCL4 in serum and CSF, with a correlation coefficient of r = 0.92 (95% CI = 0.20-0.99, p = 0.027). We gathered more clinical samples to provide further validation of the abundance of CCL4 expression. A clinical study analyzing serum samples from 19 glioma patients and 22 patients with central nervous system inflammation diseases revealed that CCL4 levels were notably elevated in the inflammatory group compared with the glioma group (p < 0.001). These results suggest that assessing serum CCL4 levels may be useful in distinguishing those patients for clinical diagnostic purposes. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer (BC) is a common cancer characterized by a high molecular heterogeneity. Therefore, understanding its biological properties and developing effective treatments for patients with different molecular features is imperative. Calcium-sensing receptor (CaSR) has been implicated in several regulatory functions in various types of human cancers. However, its underlying pathological mechanism in BC progression remains elusive. Methods: We utilized The Cancer Genome Atlas and Gene Expression Omnibus databases to explore the function of CaSR in the metastasis of BC. Gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and Gene Set Enrichment Analysis of biological processes and cell signaling pathways revealed that CaSR could be activated or inhibited. Importantly, quantitative reverse transcriptase-polymerase chain reaction and western blotting were used to verify the gene expression of the CaSR. Wound healing and transwell assays were conducted to assess the effect of CaSR on the migration of BC cells. Results: We demonstrated that CaSR expression in metastatic BC was higher than that in non-metastatic BC. It is the first time that database information has been used to reveal the biological process and molecular mechanism of CaSR in BC. Moreover, the CaSR expression in normal breast epithelial cells was notably less compared to that in BC cells. The activation of CaSR by Cinacalcet (a CaSR agonist) significantly enhanced the migration of BC cells, whereas NPS-2143 (a CaSR antagonist) treatment dramatically inhibited these effects. Conclusion and future perspective: Bioinformatics techniques and experiments demonstrated the involvement of CaSR in BC metastasis. Our findings shed new light on the receptor therapy and molecular pathogenesis of BC, and emphasize the crucial function of CaSR, facilitating the metastasis of BC. [ABSTRACT FROM AUTHOR]

Neuropeptides are endogenous active substances within the central and peripheral nervous systems that play important roles in a wide range of brain functions, including metabolism, food intake, social behavior, reproduction, learning, sleep, and wakefulness. This article reviews recent advances in the involvement of neuropeptides in vascular dementia. Neuropeptides are present in the brain as chemical signals and last for nearly 50 years. Peptide hormones are chemical signals of the endocrine system. Thus, neuropeptides are the most diverse class of signaling molecules in the brain, involving the genomes of many mammals, encoding neuropeptide precursors and many bioactive neuropeptides. Here the aim is to describe the recent advances in classical neuropeptides, as well as putative neuropeptides from other families, in the control of or as diagnostic tools for vascular dementia. Additionally, its molecular mechanisms are described to explore new avenues of treatment and early diagnosis, as there is increasing evidence that dysregulation of vascular processes is associated with different pathological conditions. [ABSTRACT FROM AUTHOR]

This study aimed to explore the liver protective effects of a fourth-generation glycyrrhizic acid product (magnesium isoglycyrrhizinate injection, MII) in the treatment of mice with drug-induced liver injury—specifically, to determine its effects on plasma metabolites. Moreover, the possible mechanism of its intervention in lipid metabolism and amino acid metabolism through the liver protective effect was preliminarily explored, combined with network pharmacology. The liver injury model of mice was established using acetaminophen (APAP). The protective effect of MII on the mice model was evaluated using pathological tissue sections and biochemical indices such as alanine transaminase (ALT), aspartate aminotransferase (AST), and superoxide dismutase (SOD). Metabolomics analysis of plasma was performed using the UHPLC-QTOF/MS technique to screen for potential biomarkers and enriched metabolic pathways. The potential targets and pathways of MII were predicted by network pharmacology, and the mechanism was verified by Western blot analysis. MII significantly improved the pathological liver changes in mice with liver injury. The content of ALT and AST was decreased, and the activity of SOD was increased significantly (p < 0.05, 0.01). A total of 29 potential biomarkers were identified in the metabolomics analysis, mainly involving seven pathways, such as lipid metabolism and amino acid metabolism. A total of 44 intersection targets of MII in the treatment of liver injury were obtained by network pharmacology, involving lipid metabolism and other related pathways. Western blot analysis results showed that MII could significantly reduce the expression of JAK2 and STAT3. MII can effectively ameliorate liver injury in modeled mice through related pathways such as lipid metabolism and amino acid metabolism. This study could provide not only a scientific basis for the elucidation of the mechanism of action of MII in exerting a hepatoprotective effect, but also a reference for its rational clinical application.

Objective: DNA methylation plays a potential role in the pathogenesis of Alzheimer's disease (AD). However, little is known about the global changes of blood leukocyte DNA methylome profiles from Chinese patients with mild cognitive impairment (MCI) and with AD, or the specific DNA methylationbased signatures associated with MCI and AD. In this study, we sought to dissect the characteristics of blood DNA methylome profiles in MCI- and ADaffected Chinese patients with the aim of identifying novel DNA methylation biomarkers for AD. Methods: In this study, we profiled the DNA methylome of peripheral blood leukocytes from 20 MCI- and 20 AD-affected Chinese patients and 20 cognitively healthy controls (CHCs) with the Infinium Methylation EPIC BeadChip array. Results: We identified significant alterations of the methylome profiles in MCI and AD blood leukocytes. A total of 2,582 and 20,829 CpG sites were significantly and differentially methylated in AD and MCI compared with CHCs (adjusted p < 0.05), respectively. Furthermore, 441 differentially methylated positions (DMPs), aligning to 213 unique genes, were overlapped by the three comparative groups of AD versus CHCs, MCI versus CHCs, and AD versus MCI, of which 6 and 5 DMPs were continuously hypermethylated and hypomethylated in MCI and AD relative to CHCs (adjusted p < 0.05), respectively, such as FLNC cg20186636 and AFAP1 cg06758191. The DMPs with an area under the curve >0.900, such as cg18771300, showed high potency for predicting MCI and AD. In addition, gene ontology and pathway enrichment results showed that these overlapping genes were mainly involved in neurotransmitter transport, GABAergic synaptic transmission, signal release from synapse, neurotransmitter secretion, and the regulation of neurotransmitter levels. Furthermore, tissue expression enrichment analysis revealed a subset of potentially cerebral cortex-enriched genes associated with MCI and AD, including SYT7, SYN3, and KCNT1. Conclusion: This study revealed a number of potential biomarkers for MCI and AD, also highlighted the presence of epigenetically dysregulated gene networks that may engage in the underlying pathological events resulting in the onset of cognitive impairment and AD progression. Collectively, this study provides prospective cues for developing therapeutic strategies to improve cognitive impairment and AD course. [ABSTRACT FROM AUTHOR]

Background: Sjögren's syndrome (SS) is a systemic autoimmune disease that affects about 0.04-0.1% of the general population. SS diagnosis depends on symptoms, clinical signs, autoimmune serology, and even invasive histopathological examination. This study explored biomarkers for SS diagnosis. Methods: We downloaded three datasets of SS patients' and healthy pepole's whole blood (GSE51092, GSE66795, and GSE140161) from the Gene Expression Omnibus (GEO) database. We used machine learning algorithm to mine possible diagnostic biomarkers for SS patients. Additionally, we assessed the biomarkers' diagnostic value using the receiver operating characteristic (ROC) curve. Moreover, we confirmed the expression of the biomarkers through the reverse transcription quantitative polymerase chain reaction (RT-qPCR) using our own Chinese cohort. Eventually, the proportions of 22 immune cells in SS patients were calculated by CIBERSORT, and connections between the expression of the biomarkers and immune cell ratios were studied. Results: We obtained 43 DEGs that were mainly involved in immune-related pathways. Next, 11 candidate biomarkers were selected and validated by the validation cohort data set. Besides, the area under curves (AUC) of XAF1, STAT1, IFI27, HES4, TTC21A, and OTOF in the discovery and validation datasets were 0.903 and 0.877, respectively. Subsequently, eight genes, including HES4, IFI27, LY6E, OTOF, STAT1, TTC21A, XAF1, and ZCCHC2,were selected as prospective biomarkers and verified by RT-qPCR. Finally, we revealed the most relevant immune cells with the expression of HES4, IFI27, LY6E, OTOF, TTC21A, XAF1, and ZCCHC2. Conclusion: In this paper, we identified seven key biomarkers that have potential value for diagnosing Chinese SS patients. [ABSTRACT FROM AUTHOR]

Abstract Objective This study identified underlying genetic molecules associated with histologically unstable carotid atherosclerotic plaques through bioinformatics analysis that may be potential biomarkers and therapeutic targets. Methods Three transcriptome datasets (GSE41571, GSE120521 and E-MTAB-2055) and one non-coding RNA dataset (GSE111794) that met histological grouping criteria of unstable plaque were downloaded. The common differentially expressed genes (co-DEGs) of unstable plaques identified from three mRNA datasets were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG). A protein–protein interaction (PPI) network was constructed to present the interaction between co-DEGs and screen out hub genes. MiRNet database and GSE111794 dataset were used to identify the miRNAs targeting hub genes. Associated transcription factors (TFs) and drugs were also predicted. These predicted results were used to construct miRNA/TFs-hub gene and drug-hub gene regulatory networks. Results A total of 105 co-DEGs were identified, including 42 up-regulated genes and 63 down-regulated genes, which were mainly enriched in collagen-containing extracellular matrix, focal adhesion, actin filament bundle, chemokine signaling pathway and regulates of actin cytoskeleton. Ten hub genes (up-regulated: HCK, C1QC, CD14, FCER1G, LCP1 and RAC2; down-regulated: TPM1, MYH10, PLS3 and FMOD) were screened. HCK and RAC2 were involved in chemokine signaling pathway, MYH10 and RAC2 were involved in regulation of actin cytoskeleton. We also predicted 12 miRNAs, top5 TFs and 25 drugs targeting hub genes. In the miRNA/TF-hub gene regulatory network, PLS3 was the most connected hub genes and was targeted by six miRNAs and all five screened TFs. In the drug-hub gene regulatory network, HCK was targeted by 20 drugs including 10 inhibitors. Conclusions We screened 10 hub genes and predicted miRNAs and TFs targeting them. These molecules may play a crucial role in the progression of histologically unstable carotid plaques and serve as potential biomarkers and therapeutic targets.

Epithelial-mesenchymal transition (EMT) is critical in the development of coronary artery disease (CAD). However, landscapes of EMT-related genes have not been fully established in CAD. We identified the differentially expressed mRNAs and lncRNAs (DElncRNAs) from the Gene Expression Omnibus database. Pearson’s correlation analysis, the least absolute shrinkage and selection operator regression, and support vector machine reverse feature elimination algorithms were used to screen EMT-related lncRNAs. The cis–trans regulatory networks were constructed based on EMT-related lncRNAs. Quantitative real-time polymerase chain reaction was performed to validate the expression of EMT-related genes in a cohort of six patients with CAD and six healthy controls. We further estimated the infiltration of the immune cells in CAD patients with five algorithms, and the correlation between EMT-related genes and infiltrating immune cells was analyzed. We identified eight EMT-related lncRNAs in CAD. The area under curve value was greater than 0.95. The immune analysis revealed significant CD8 T cells, monocytes, and NK cells in CAD and found that EMT-related lncRNAs were correlated with these immune cell subsets. Moreover, SNAI2, an EMT-TF gene, was found in the trans-regulatory network of EMT-related lncRNAs. Further, we found SNAI2 as a biomarker for the diagnosis of CAD but it also had a close correlation with immune cell subsets in CAD. Eight EMT-related lncRNAs and SNAI2 have important significance in the diagnosis of CAD patients.

ABSTRACT: Avian neurotropic viruses are critical problems in poultry industry causing severe central nervous system (CNS) damage with neuroinvasive and neurovirulence properties. Biomarker of neurotropic viral intracranial invasion is of great application value for the diagnosis, but that of avian neurotropic viruses remains elusive. Previously, we found that chicken caspase recruitment domain family, member 11 (CARD11) was only upregulated in virulent Newcastle disease virus-infected chickens and in chicken primary neuronal cells. In this study, CARD11 was systemically expressed in chickens and pigeons detected by absolute qPCR and immunohistochemical (IHC) assay. After virus challenging, only avian neurotropic viruses (avian encephalomyelitis virus [AEV] and pigeon paramyxovirus type 1 [PPMV-1]) except Marek's disease virus (MDV) can invade brain and cause pathological changes. The relative mRNA expression of CARD11 was brain-upregulated in AEV- or PPMV-1-infected animals, rather than MDV and non-neurotropic viruses (fowl adenovirus serotype 4 [FAdV-4] and infectious bronchitis virus [IBV]). Similarly, the protein expression of CARD11 was only upregulated in the cerebra and cerebella infected by avian brain-neurotropic virus using IHC assay. And there were no correlations between the change level of CARD11 and viral load. Our preliminary data suggested that avian CARD11 may be a potential brain biomarker for avian brain-neurotropic virus invasion.

Background: Breast cancer (BC) has recently become the most prevalent malignancy in women. There are many alternative treatments for BC, and for aesthetic and postoperative quality of life concerns, breast-conserving surgery and corresponding adjuvant therapy have become the predominant treatment for early invasive BC. Currently, the main method used to assess the margins for breast-conserving surgery is intraoperative pathological diagnosis. However, the designation of surgical margins is controversial, and metabolomics may be a novel approach to evaluate surgical margins. Methods: We collected specimens from 10 breast cancer patients and samples from its surrounding tissues and divided them into cancerous tissue and 1 mm, 2 mm, 3 mm, 5mmand 10mmcutting edge tissues, with a total of 60 samples. The samples were analyzed by mass spectrometry on an ultra-performance liquid chromatography-quadrupole/Orbitrap high resolution platform. The data were then statistically analyzed to detect metabolic changes in the different cutting edges and to identify possible surgical cutting edges with statistically significant findings. Abnormal metabolic pathways were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG), which elucidated potential markers. Results: Statistical analysis indicated that there were substantial differences between the 1 mm margin tissue and the cancer tissue, while there were no statistically significant differences between the 1 mm tissue and tissues from the other margins. The levels of 6 metabolites in the 1 mm tissue were significantly different from those in the cancer tissue and were not significantly different from those in the 2 mm tissue. The six metabolites were pyruvate, N-acetyl-L-aspartate, glutamic acid, γ-aminobutyric acid, fumaric acid, and citric acid. Metabolic pathways such as amino acid metabolism and amino t-RNA synthesis in the margin tissue were significantly distinct from those in cancer tissues based on KEGG analysis. Conclusion: There was a significant difference between the 1mmmargin tissue and the cancerous tissue. Based on metabolomic analysis, the 1 mm negative margin is sufficient for surgery, and the six metabolites that we identified as abnormal, including pyruvic acid, N-acetyl-L-aspartic acid, glutamic acid, gamma-aminobutyric acid, fumaric acid and citric acid, may serve as biomarkers for a negative margin and help surgeons select an appropriate surgical margin. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a multifactorial, complex, and aggressive disease with a prevalence of one million new cases and high global mortality. Factors such as genetic, epigenetic, and environmental changes contribute to the onset and progression of the disease. Identification of INDELs in miRNA and its target sites in current studies showed an important role in the development of cancer. In GC, miRNAs act as oncogenes or tumor suppressors, favoring important cancer pathways, such as cell proliferation and migration. This work aims to investigate INDELs in the coding region of miRNAs (hsa-miR-302c, hsa-miR-548AJ-2, hsa-miR-4274, hsa-miR-630, hsa-miR-516B-2, hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920, has-mir-3171, and hsa-miR-3652) that may be associated with susceptibility and clinical variants of gastric cancer. For this study, 301 patients with GC and 145 individuals from the control group were selected from an admixed population in the Brazilian Amazon. The results showed the hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920 and hsa-miR-3652 variants were associated with gastric cancer susceptibility. The hsa-miR-4463 was significantly associated with clinical features of GC such as diffuse gastric tumor histological type, "non-cardia" localization region, and early onset. Our findings indicated that INDELs could be potentially functional genetic variants for gastric cancer risk. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of our study is to identify potential biomarkers of hepatoblastoma (HB) and further explore the pathogenesis of it. Methods: Differentially expressed genes (DEGs) were incorporated into the combined random forest and artificial neural network diagnosis model to screen candidate genes for HB. Gene set enrichment analysis (GSEA) was used to analyze the ARHGEF2. Student's t test was performed to evaluate the difference of tumor-infiltrating immune cells (TIICs) between normal and HB samples. Spearson correlation analysis was used to calculate the correlation between ARHGEF2 and TIICs. Results: ARHGEF2, TCF3, TMED3, STMN1 and RAVER2 were screened by the new model. The GSEA of ARHGEF2 included cell cycle pathway and antigen processing presenting pathway. There were significant differences in the composition of partial TIICs between HB and normal samples (p < 0.05). ARHGEF2 was significantly correlated with memory B cells (Cor = 0.509, p < 0.05). Conclusion: These 5 candidate genes contribute to the molecular diagnosis and targeted therapy of HB. And we found "ARHGEF2–RhoA–Cyclin D1/CDK4/CDK6–EF2" is a key mechanism regulating cell cycle pathway in HB. This will be helpful in the treatment of HB. The occurrence of HB is related to abnormal TIICs. We speculated that memory B cells play an important role in HB. [ABSTRACT FROM AUTHOR]

Introduction: Pneumoconiosis represents the most prevalent occupational disease in China, with coal workers' pneumoconiosis (CWP) showing the highest incidence. Analysis of volatile organic compounds (VOCs) in the exhaled breath of CWP patients may provide novel insights into its pathogenesis., Methods: Study data were collected through questionnaires and medical examinations. Thermal desorption-gas chromatography-mass spectrometry was employed for targeted VOC analysis. Differential VOCs were identified using OPLS-DA, the Mann-Whitney U test, and fold change analysis. The discriminatory efficacy of differential VOCs was evaluated using receiver operating characteristic (ROC) curves. Spearman correlation analysis explored relationships between differential VOCs, lung function indices, and blood cell levels., Results: The pneumoconiosis group showed elevated concentrations of 10 compounds, including isopentane, n-pentane, and isoprene, while four compounds, including 2,4-dimethylpentane, methylcyclohexane, 2,3,4-trimethylpentane, and 2-methylheptane showed decreased concentrations. Combined univariate and multivariate statistical analyses identified six significant VOCs, including isopentane and pentane. Notably, isopentane and n-pentane demonstrated negative correlations with forced vital capacity and levels, while 2-methylheptane showed positive correlations., Discussion: Clear metabolic differences in VOCs exist between CWP patients and non-dust-exposed healthy controls. Six compounds - isopentane, n-pentane, 3-methylpentane, n-hexane, cyclohexane, and 2-methylheptane - in exhaled breath demonstrate potential as biomarkers for CWP., Competing Interests: No conflicts of interest., (Copyright © 2024 by Chinese Center for Disease Control and Prevention.)

Abstract Bladder cancer (BC) is one of the most frequent cancer in the world, and its incidence is rising worldwide, especially in developed countries. Urine metabolomics is a powerful approach to discover potential biomarkers for cancer diagnosis. In this study, we applied an ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) method to profile the metabolites in urine from 29 bladder cancer patients and 15 healthy controls. The differential metabolites were extracted and analyzed by univariate and multivariate analysis methods. Together, 19 metabolites were discovered as differently expressed biomarkers in the two groups, which mainly related to the pathways of phenylacetate metabolism, propanoate metabolism, fatty acid metabolism, pyruvate metabolism, arginine and proline metabolism, glycine and serine metabolism, and bile acid biosynthesis. In addition, a subset of 11 metabolites of those 19 ones were further filtered as potential biomarkers for BC diagnosis by using logistic regression model. The results revealed that the area under the curve (AUC) value, sensitivity and specificity of receiving operator characteristic (ROC) curve were 0.983, 95.3% and 100%, respectively, indicating an excellent discrimination power for BC patients from healthy controls. It was the first time to reveal the potential diagnostic markers of BC by metabolomics, and this will provide a new sight for exploring the biomarkers of the other disease in the future work.

Objective: This study identified underlying genetic molecules associated with histologically unstable carotid atherosclerotic plaques through bioinformatics analysis that may be potential biomarkers and therapeutic targets. Methods: Three transcriptome datasets (GSE41571, GSE120521 and E-MTAB-2055) and one non-coding RNA dataset (GSE111794) that met histological grouping criteria of unstable plaque were downloaded. The common differentially expressed genes (co-DEGs) of unstable plaques identified from three mRNA datasets were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG). A protein–protein interaction (PPI) network was constructed to present the interaction between co-DEGs and screen out hub genes. MiRNet database and GSE111794 dataset were used to identify the miRNAs targeting hub genes. Associated transcription factors (TFs) and drugs were also predicted. These predicted results were used to construct miRNA/TFs-hub gene and drug-hub gene regulatory networks. Results: A total of 105 co-DEGs were identified, including 42 up-regulated genes and 63 down-regulated genes, which were mainly enriched in collagen-containing extracellular matrix, focal adhesion, actin filament bundle, chemokine signaling pathway and regulates of actin cytoskeleton. Ten hub genes (up-regulated: HCK, C1QC, CD14, FCER1G, LCP1 and RAC2; down-regulated: TPM1, MYH10, PLS3 and FMOD) were screened. HCK and RAC2 were involved in chemokine signaling pathway, MYH10 and RAC2 were involved in regulation of actin cytoskeleton. We also predicted 12 miRNAs, top5 TFs and 25 drugs targeting hub genes. In the miRNA/TF-hub gene regulatory network, PLS3 was the most connected hub genes and was targeted by six miRNAs and all five screened TFs. In the drug-hub gene regulatory network, HCK was targeted by 20 drugs including 10 inhibitors. Conclusions: We screened 10 hub genes and predicted miRNAs and TFs targeting them. These molecules may play a crucial role in the progression of histologically unstable carotid plaques and serve as potential biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

The identification of ante- and post-mortem burns is challenging in forensic pathology. In this study, microarray analysis was used to detect the mRNA expression profiles in the skin of an experimental burn mouse model; the results were validated using RT-qPCR. Differentially expressed mRNAs (DE-mRNAs) were assessed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Our results revealed that mRNA expression of 501 genes was significantly different, of which 273 were upregulated and 228 were downregulated in ante-mortem burned mice skin. The expression levels of eight random mRNAs were consistent when measured using the microarray assay-based method and RT-qPCR. Genes from different functional categories and signalling pathways were enriched, including interleukin-20 binding, type IV hypersensitivity, negative regulation of acute inflammatory response, sensory organ development, endocytosis, neuroactive ligand-receptor interaction, and Jak-STAT signalling pathway. Only five of the eight mRNAs exhibited consistent changes in expression between burned skin samples of mice and human autopsy specimens. Our findings showed that DE-mRNAs revealed using microarray are potential biomarkers of ante-mortem burns. However, DE-mRNAs identified from experimental animal models cannot be directly extended to autopsy specimens without careful validation. [ABSTRACT FROM AUTHOR]

Background: UC is a chronic, relapsing and remitting inflammatory condition of the colon. The diagnosis of UC is based on signs, symptoms, endoscopic evaluation, and histologic parameters. Accurate diagnosis and disease staging are important as these affect treatment options and prognosis. The main target in UC treatment is mucosal healing, which is related to longterm remission, reduced rates of hospitalization, and colectomy. Despite the advantages in the management of UC over the past few decades, much less has been achieved in the diagnosis and monitoring of the disease where colonoscopy remains the "gold standard" method. Therefore, a non-invasive marker correlating with mucosal healing is being sought. Aim of the Work: to evaluate the role of serum gelsolin level (SGN) as a simple, easy, and available predictor for mucosal healing in patients with ulcerative colitis as compared to endoscopic scores and other widely used laboratory biomarkers. Patients and Methods: The present study was conducted on 40 patients with clinical, biochemical, and endoscopic active UC and followed up during disease activity and remission. All patients were subjected to full history taking, clinical examination, routine laboratory investigations, ESR and CRP, CBC, fecal calprotectin, SGN, colonoscopy and biopsies with histopathological examination. Results: The current study revealed a statistically significantly higher TLC, Platelet count, CRP, ESR and Fecal calprotectin among disease activity in relation to remission. However, serum gelsolin level, hemoglobin and albumin levels were statistically significantly lower in activity patients in comparison to remission patients. There was no statistically significant relation between SGN and gender, different laboratory parameters. There was statistically significant relation between SGN and mayo endoscopic sore as it has the highest level in MES 0. In the present study, SGN was found to be higher in patients with clinical and endoscopic remission and healing with statistically significant correlation with endoscopicmucosal scores representingmucosal healing like Mayo score and UCEIS and may be a possible useful marker for predicting endoscopic activity andmucosal healing in UC patients. It would be more helpful when used together with serum laboratory inflammatory indices (ESR, CRP and fecal calprotectin). Conclusion: Serum gelsolin level can be used for prediction of mucosal healing in ulcerative colitis and endoscopic activity. A greater sample size would have resulted in more reliable subgroup analyses for UC. Larger studies are needed to be conducted to be conclude correlation between SGN and endoscopic scores and microscopic histopathological scores. [ABSTRACT FROM AUTHOR]

Objective: To propose and verify that miRNA‐31 increases the radiosensitivity of colorectal cancer and explore its potential mechanism. Method: A bioinformatics analysis was performed to confirm that the expression of miRNA‐31 was higher in colorectal cancer than in normal colorectal tissue. The expression of miRNA‐31 was detected to verify the change in its expression in a radiotherapy‐resistant cell line. Methylation was detected to explore the cause of the decrease in miRNA‐31 expression. Overexpression or inhibition of miRNA‐31 further confirmed the change in its expression in colorectal cancer cell lines. Bioinformatics methods were used to screen the downstream target genes and for experimental verification. A luciferase assay was performed to determine the miRNA‐31 binding site in STK40. Overexpression or inhibition of STK40 in colorectal cancer cell lines further confirmed the change in STK40 expression in vitro. Results: The bioinformatics results showed higher expression of miRNA‐31 in tumors than in normal tissue, and miRNA‐31 mainly participated in the pathway related to cell replication. Next, we observed the same phenomenon: miRNA‐31 was expressed at higher levels in colorectal tumors than in normal colorectal tissue and its expression decreased in radiation‐resistant cell lines after radiation, implying that miRNA‐31 increased the radiosensitivity of colorectal cancer cell lines. No significant change in upstream methylation was observed. miRNA‐31 regulated the radiosensitivity of colorectal cancer cell lines by inhibiting STK40. Notably, miRNA‐31 played a role by binding to the 3′ untranslated region of SK40. STK40 negatively regulated the radiosensitivity of colorectal cancer cells. Conclusions: miRNA‐31 increases the radiosensitivity of colorectal cancer cells by targeting STK40; miRNA‐31 and STK40 are expected to become potential biomarkers for increasing the sensitivity of tumor radiotherapy in clinical treatment. [ABSTRACT FROM AUTHOR]

Background: Cases of tuberculosis (TB) and multidrug-resistant TB (MDR-TB) in South-east Asia including Indonesia are still high. The presence of mixed infections in TB cases has been reported. Several studies revealed the role of the human microbiome in TB. This study purposes to characterize microbiome which can be a potential biomarker of chronicity in TB or MDR-TB. Methods: Sputum samples of pulmonary TB patients confirmed MDR-TB and resistant to rifampicin TB (RR-TB) were conducted Metagenomic next-generation sequencing. Principal coordinate analysis of UniFrac's showing the community structure of microbiome in MDR-TB comorbid diabetes mellitus (DM) is different from RR-TB noncomorbid DM (P = 0.003). Results: Proteobacteria microbiome in MDR-TB comorbid DM was more abundant than in RR-TB noncomorbid DM. Actinobacteria found in the small quantity in RR-TB and MDR-TB. Diversity of microbiome genera was greater in RR-TB. The linear discriminant analysis effect size analysis represents a genus biomarker whose abundance shows significant differences between groups, genus Rothia as a potential biomarker for RR-TB noncomorbid DM. Conclusions: Interesting findings is the community structure of microbiome in MDR-TB and RR-TB. In chronic TB such as recurrent, associated MDR-TB should attention to the findings of a small number of Actinobacteria could be a biomarker of TB which is also a determinant in patient taking combined anti-TB drugs of choice.

Despite emerging publications have elucidated a functional association between RCN3 and tumors, no evidence about a pan-cancer analysis of RCN3 is available. Our study first conducted a comprehensive assessment of its expression profiles, prognosis value, immune infiltration, and relevant cellular pathways via bioinformatics techniques based on the public database of TCGA (The Cancer Genome Atlas). RCN3 is highly expressed in most tumors, and it is associated with poor prognosis. Kaplan-Meier analysis and Cox regression analysis suggested that the high expression of RCN3 was associated with poor overall survival (OS) in pan-cancer, Cox regression analysis also indicated high RCN3 expression was correlated with disease-specific survival (DSS) and progression-free interval (PFI) in most tumors. We observed a regulation function of RCN3 at genetic and epigenetic levels through CNA and DNA methylation using cBioPortal database. Based on Gene Set Enrichment Analysis, we first identified related pathways of RCN3 and its potential biological functions in pan-cancer, RCN3 was implicated in oncogenic pathways, and was related to extracellular matrix and immune regulation. We found that RCN3 positively correlated with the levels of infiltrating cells such as TAMs and CAFs, but negatively correlated with CD8+ T-cells by analyzing immune cell infiltration data we downloaded from published work and online databases, further investigation of the correlation between immunosuppressive genes, chemokines, chemokines receptors, and high RCN3 expression showed a significant positive association in the vast majority of TCGA cancer types. These results indicated its role as an immune regulatory in cancers and suggested that RCN3 is a potential biomarker for immunotherapy. Also, we found that expression of RCN3 was much higher in CRC tissues than in normal tissues with a higher expression level of RCN3 closely correlating to advanced American Joint Committee on Cancer (AJCC) stage, poor differentiation, increased tumor size, and poor prognosis of CRC. Biological function experiments showed that RCN3 regulated CRC cells' proliferation and metastasis ability. Upregulation of RCN3 in CRC cells increased the expression of immune related factor, including TGFβ1, IL-10, and IL-6. Thus, our pan-cancer analysis offers a deep understanding of potential oncogenic roles of RCN3 in different cancers. [ABSTRACT FROM AUTHOR]

Despite emerging publications have elucidated a functional association between RCN3 and tumors, no evidence about a pan-cancer analysis of RCN3 is available. Our study first conducted a comprehensive assessment of its expression profiles, prognosis value, immune infiltration, and relevant cellular pathways via bioinformatics techniques based on the public database of TCGA (The Cancer Genome Atlas). RCN3 is highly expressed in most tumors, and it is associated with poor prognosis. Kaplan-Meier analysis and Cox regression analysis suggested that the high expression of RCN3 was associated with poor overall survival (OS) in pan-cancer, Cox regression analysis also indicated high RCN3 expression was correlated with disease-specific survival (DSS) and progression-free interval (PFI) in most tumors. We observed a regulation function of RCN3 at genetic and epigenetic levels through CNA and DNA methylation using cBioPortal database. Based on Gene Set Enrichment Analysis, we first identified related pathways of RCN3 and its potential biological functions in pan-cancer, RCN3 was implicated in oncogenic pathways, and was related to extracellular matrix and immune regulation. We found that RCN3 positively correlated with the levels of infiltrating cells such as TAMs and CAFs, but negatively correlated with CD8+ T-cells by analyzing immune cell infiltration data we downloaded from published work and online databases, further investigation of the correlation between immunosuppressive genes, chemokines, chemokines receptors, and high RCN3 expression showed a significant positive association in the vast majority of TCGA cancer types. These results indicated its role as an immune regulatory in cancers and suggested that RCN3 is a potential biomarker for immunotherapy. Also, we found that expression of RCN3 was much higher in CRC tissues than in normal tissues with a higher expression level of RCN3 closely correlating to advanced American Joint Committee on Cancer (AJCC) stage, poor differentiation, increased tumor size, and poor prognosis of CRC. Biological function experiments showed that RCN3 regulated CRC cells’ proliferation and metastasis ability. Upregulation of RCN3 in CRC cells increased the expression of immune related factor, including TGFβ1, IL-10, and IL-6. Thus, our pan-cancer analysis offers a deep understanding of potential oncogenic roles of RCN3 in different cancers.

Although HER2-low breast cancer (BC) constitutes almost 50% of all BC types, its impact on the pathological complete response (pCR) rate and survival in early BC is uncertain. As a result, a systematic review was conducted to compare the pCR rate and survival of HER2-low and HER2-zero BC in the neoadjuvant chemotherapy (NACT) setting. Two reviewers independently performed literature searches using EMBASE, PubMed, and Cochrane Libraries internet databases up to June 2023. Finally, 29 studies with 178,294 patients were included. HER2-low BC had a considerably lower pCR rate compared to HER2-zero BC in the entire population (Risk Ratio [RR] = 0.68, P < .001) and in the hormone receptor (HR)-positive subgroup (RR = 0.73, P = .009), but not in the HR-negative subgroup (RR = 0.99, P = .755). Furthermore, patients with HER2-low BC exhibited prolonged disease-free survival (DFS) and overall survival (OS) compared to those with HER2-zero BC, observed in both the entire cohort (DFS: P = .004; OS: P = .008) and the HR-negative subgroup (DFS: P = .009; OS: P < .001). In the HR-positive population, OS was superior in HER2-low BC patients (P < .001), whereas no significant differences in DFS were observed (P = .064). Our findings imply that the pCR rate and prognosis of HER2-low BC are distinguished from those of HER2-zero BC in early BC treated with NACT, which contributes to a better knowledge of the BC subgroup., (Copyright © 2024. Published by Elsevier Inc.)

Bladder cancer (BC) is one of the most frequent cancer in the world, and its incidence is rising worldwide, especially in developed countries. Urine metabolomics is a powerful approach to discover potential biomarkers for cancer diagnosis. In this study, we applied an ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) method to profile the metabolites in urine from 29 bladder cancer patients and 15 healthy controls. The differential metabolites were extracted and analyzed by univariate and multivariate analysis methods. Together, 19 metabolites were discovered as differently expressed biomarkers in the two groups, which mainly related to the pathways of phenylacetate metabolism, propanoate metabolism, fatty acid metabolism, pyruvate metabolism, arginine and proline metabolism, glycine and serine metabolism, and bile acid biosynthesis. In addition, a subset of 11 metabolites of those 19 ones were further filtered as potential biomarkers for BC diagnosis by using logistic regression model. The results revealed that the area under the curve (AUC) value, sensitivity and specificity of receiving operator characteristic (ROC) curve were 0.983, 95.3% and 100%, respectively, indicating an excellent discrimination power for BC patients from healthy controls. It was the first time to reveal the potential diagnostic markers of BC by metabolomics, and this will provide a new sight for exploring the biomarkers of the other disease in the future work. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT) is critical in the development of coronary artery disease (CAD). However, landscapes of EMT-related genes have not been fully established in CAD. We identified the differentially expressed mRNAs and lncRNAs (DElncRNAs) from the Gene Expression Omnibus database. Pearson’s correlation analysis, the least absolute shrinkage and selection operator regression, and support vector machine reverse feature elimination algorithms were used to screen EMTrelated lncRNAs. The cis–trans regulatory networks were constructed based on EMT-related lncRNAs. Quantitative real-time polymerase chain reaction was performed to validate the expression of EMT-related genes in a cohort of six patients with CAD and six healthy controls. We further estimated the infiltration of the immune cells in CAD patients with five algorithms, and the correlation between EMTrelated genes and infiltrating immune cells was analyzed. We identified eight EMT-related lncRNAs in CAD. The area under curve value was greater than 0.95. The immune analysis revealed significant CD8 T cells, monocytes, and NK cells in CAD and found that EMT-related lncRNAs were correlated with these immune cell subsets. Moreover, SNAI2, an EMT-TF gene, was found in the trans-regulatory network of EMT-related lncRNAs. Further, we found SNAI2 as a biomarker for the diagnosis of CAD but it also had a close correlation with immune cell subsets in CAD. Eight EMT-related lncRNAs and SNAI2 have important significance in the diagnosis of CAD patients. [ABSTRACT FROM AUTHOR]

Microplastics are ubiquitously present in the environment, accumulate in aquaculture water, and cause toxicological effects on aquatic organisms. Besides, microplastics provide ecological niches for microorganisms in aquatic environments. However, the effects of microplastics on microbial balance and function in surrounding water are still unclear, especially for aquaculture water. Therefore, 16S rRNA gene sequencing was employed to uncover polystyrene microplastics (PS)-induced microbial dysbiosis in surrounding seawater cultivating marine medaka (Oryzias melastigmas) and to screen related potential bacterial biomarkers. We found that Proteobacteria and Bacteroidetes were the dominant phyla in each group, accounting for more than 95% of the total abundance, and that 26 bacterial taxa belonging to Proteobacteria and Bacteroidetes were significantly altered in surrounding seawater after 10- and 200-µm PS exposure. Functional analysis revelated that photosynthesis, carbon metabolism (such as carbon fixation, glycolysis, tricarboxylic acid cycle, and glycan biosynthesis and metabolism), amino acid metabolism, lipid synthesis, and nucleotide metabolism were decreased, while environmental stress responses, such as xenobiotics biodegradation and metabolism, glutathione metabolism, and taurine and hypotaurine metabolism, were increased in surrounding seawater microbiota after separate 10- and 200-µm PS exposure. Pathway analysis and correlation networks demonstrated that changes in relative abundances of bacterial taxa belonging to Proteobacteria and Bacteroidetes were highly correlated with those in the liver metabolism of marine medaka. Subsequently, 8 bacterial taxa were discovered to be able to be used separately as the potential biomarker for assessing the surrounding seawater microbial dysbiosis and metabolic responses of marine medaka, with a diagnostic accuracy of 100.0%. This study provides novel insights into toxicological effects of microplastics on microbial dysbiosis and function in surrounding water and ecosystems, and suggests potential roles of biomarkers involved in surrounding microbial dysbiosis in assessing microplastic ecotoxicology, microbial dysbiosis, and the health status of organisms at higher trophic levels.

Postoperative neurocognitive disorders (po-NCD), including postoperative delirium (POD) and delayed neurocognitive recovery (dNCR), are common in geriatric surgical patients. However, the ideal diagnostic biomarkers to predict individual risks of po-NCDs have not been identified. In this study, proteomic analysis was used to detect dysregulated proteins in three cognitive-related brain regions, the hippocampus, prefrontal cortex, and temporal lobe, of aged dNCR rats. The common affected proteins in these three brain regions were further verified by real-time polymerase chain reaction and western blotting. Furthermore, serum samples from aged rats with dNCR and elderly hip fracture patients with POD were also assessed with enzyme linked immunosorbent assays to investigate the biomarker potential of these dysregulated proteins. The increased expression levels of haptoglobin, caseinolytic protease (ClpP), and alpha-2 macroglobulin (A2M) as well as decreased expression levels of 14-3-3β/α and biliverdin reductase-A (BVR-A) were validated by proteomic analysis in the hippocampus, prefrontal cortex, and temporal lobe of aged dNCR rats. The increased expression of haptoglobin and decreased expression of 14-3-3β/α were further demonstrated in the three brain regions by western blotting. Moreover, increased levels of S100A6 and BVR-A in the hippocampus, S100A6 in the prefrontal cortex, and A2M in the temporal lobe were also observed. More intriguingly, both decreased serum 14-3-3β/α and increased A2M in geriatric POD patients as well as decreased serum ClpP in aged dNCR rats were verified. These results not only indicate potential diagnostic biomarkers for po-NCD but also provide directions for further pathological investigations.Clinical Trial Registration:www.ClinicalTrials.gov, identifier [ChiCTR1900027393].

ObjectiveSeveral studies have demonstrated the impacts of GTPases of immunity-associated proteins (GIMAPs) on malignant cells. However, the mechanisms through which Gimap5 regulates lung cancer cells are yet to be thoroughly investigated in the literature. Our study aimed to investigate the function of Gimap5 in the development of lung cancer.MethodsThe expression levels of the GIMAP family were analyzed in lung cancer patients of various cancer databases and lung cancer cell lines. After the survival rates of the cells were analyzed, we constructed Gimap5 over-expressed lung cancer cell lines and assessed the effects of Gimap5 on cell migration, cell invasion, cell proliferation and the epithelial-mesenchymal transition (EMT). We later screened the interacting proteins of Gimap5 using Co-IP combined with mass spectrometry and then analyzed the expression and distribution of M6PR, including its impacts on protein-arginine deiminase type-4 (PADI4).ResultsFindings indicated that GIMAP family expression decreased significantly in lung cancer cell lines. We also noticed that the downregulation of the GIMAP family was related to the poor prognosis of lung cancer patients. Our experimental results showed that Gimap5 could inhibit the migration, invasion, proliferation and EMT of lung cancer cell lines. Moreover, we found that Gimap5 promoted the transport of M6PR from the cytoplasm to the cell membrane, thereby inhibiting the enhancement of EMT-related PADI4.ConclusionOur research suggested that Gimap5 could inhibit the growth of lung cancer by interacting with M6PR and that it could be a potential biomarker for the diagnosis and prognosis of lung cancer.

Postoperative neurocognitive disorders (po-NCD), including postoperative delirium (POD) and delayed neurocognitive recovery (dNCR), are common in geriatric surgical patients. However, the ideal diagnostic biomarkers to predict individual risks of po-NCDs have not been identified. In this study, proteomic analysis was used to detect dysregulated proteins in three cognitive-related brain regions, the hippocampus, prefrontal cortex, and temporal lobe, of aged dNCR rats. The common affected proteins in these three brain regions were further verified by real-time polymerase chain reaction and western blotting. Furthermore, serum samples from aged rats with dNCR and elderly hip fracture patients with POD were also assessed with enzyme linked immunosorbent assays to investigate the biomarker potential of these dysregulated proteins. The increased expression levels of haptoglobin, caseinolytic protease (ClpP), and alpha-2 macroglobulin (A2M) as well as decreased expression levels of 14-3-3β/α and biliverdin reductase-A (BVR-A) were validated by proteomic analysis in the hippocampus, prefrontal cortex, and temporal lobe of aged dNCR rats. The increased expression of haptoglobin and decreased expression of 14-3-3β/α were further demonstrated in the three brain regions by western blotting. Moreover, increased levels of S100A6 and BVR-A in the hippocampus, S100A6 in the prefrontal cortex, and A2M in the temporal lobe were also observed. More intriguingly, both decreased serum 14-3-3β/α and increased A2M in geriatric POD patients as well as decreased serum ClpP in aged dNCR rats were verified. These results not only indicate potential diagnostic biomarkers for po-NCD but also provide directions for further pathological investigations. Clinical Trial Registration: www.ClinicalTrials.gov, identifier [ChiCTR1900027393]. [ABSTRACT FROM AUTHOR]

Objective: Several studies have demonstrated the impacts of GTPases of immunity-associated proteins (GIMAPs) on malignant cells. However, the mechanisms through which Gimap5 regulates lung cancer cells are yet to be thoroughly investigated in the literature. Our study aimed to investigate the function of Gimap5 in the development of lung cancer. Methods: The expression levels of the GIMAP family were analyzed in lung cancer patients of various cancer databases and lung cancer cell lines. After the survival rates of the cells were analyzed, we constructed Gimap5 over-expressed lung cancer cell lines and assessed the effects of Gimap5 on cell migration, cell invasion, cell proliferation and the epithelial-mesenchymal transition (EMT). We later screened the interacting proteins of Gimap5 using Co-IP combined with mass spectrometry and then analyzed the expression and distribution of M6PR, including its impacts on protein-arginine deiminase type-4 (PADI4). Results: Findings indicated that GIMAP family expression decreased significantly in lung cancer cell lines. We also noticed that the downregulation of the GIMAP family was related to the poor prognosis of lung cancer patients. Our experimental results showed that Gimap5 could inhibit the migration, invasion, proliferation and EMT of lung cancer cell lines. Moreover, we found that Gimap5 promoted the transport of M6PR from the cytoplasm to the cell membrane, thereby inhibiting the enhancement of EMT-related PADI4. Conclusion: Our research suggested that Gimap5 could inhibit the growth of lung cancer by interacting with M6PR and that it could be a potential biomarker for the diagnosis and prognosis of lung cancer. [ABSTRACT FROM AUTHOR]

Cryptocaryon irritans is a parasitic ciliate that causes cryptocaryonosis (white spot disease) in marine fish. Because the pathogenesis of cryptocaryonosis is unclear, and it is harmful to aquaculture, the identification of reliable biomarkers as a specific therapy for the disease is critical. To identify potential serum biomarkers in Takifugu rubripes infected by C. irritans, Agilent‐QTOF/MS‐6545 mass spectrometry‐based untargeted metabolite profiling was applied to differentiate and identify potential biomarkers in blood serum samples we collected from 10 fish infected by C. irritans and 10 healthy controls. The results of untargeted metabolic pathway analysis showed that retinol metabolism, steroid hormone biosynthesis, purine metabolism, arachidonic acid metabolism and drug metabolism involving cytochrome P450 were significantly different between infected and control groups. Based on data from the receiver operating characteristic curve, we propose that retinoic acid, progesterone, xanthosine monophosphate, hepoxilin B3, tamoxifen and prostaglandin I2 are possible potential biomarkers for infected fish in terms of both sensitivity and specificity. Our study provides new insight into the underlying mechanisms of T. rubripes infected by C. irritans, and we suggest that metabolic pathways and metabolites identified in our work could make a major contribution to the prevention and treatment of this disease in aquaculture. [ABSTRACT FROM AUTHOR]

In this work, the 4D data-independent acquisition (DIA) quantitative strategy was used for differential proteomic analysis of four beef tripe samples from different sources to explore the associations between differentially expressed proteins (DEPs) and meat quality traits. A total of 68 shared DEPs were identified in all comparison groups, which were mainly involved in phosphorylation signaling pathway, peroxisome proliferator-activated receptor (PPAR) signaling pathway, and glucuronic acid pathway. In the correlation analysis between DEPs and quality traits of beef tripe, it was found that 21 proteins were significantly associated with the quality traits in beef tripe, which could be considered as the potential biomarkers of beef tripe quality. This study has successfully uncovered the protein composition of beef tripe for the very first time, which helps to understand the key proteins and biological processes associated with the quality traits of beef tripe from different sources and improve the quality control of beef tripe. • The comprehensive study on the quality traits of beef tripe was conducted for the first time. • The differences on the quality of different kinds of beef tripe were partially explained by proteomics. • 4D-DIA proteomics identified 21 differentially expressed proteins related to quality traits of beef tripe. • Proteins that related with beef tripe quality mainly involved in oxidative stress and metabolic pathways. [ABSTRACT FROM AUTHOR]

The development of functionally enriched and biologically competent biclustering algorithm is essential for extracting hidden information from massive biological datasets. This paper presents a novel biclustering ensemble called EnsemBic based on p-value , which calculates the functional similarity of genetic associations. To validate the effectiveness and robustness of EnsemBic, we apply three well-known biclustering techniques, viz. Laplace Prior, iBBiG, and xMotif to implement EnsemBic and have been compared using different leading parameters. It is observed that the EnsemBic outperforms its competing algorithms in several prominent functional and biological measures. Next, the biclusters obtained from EnsemBic are used to identify potential biomarkers of Esophageal Squamous Cell Carcinoma (ESCC) by exploring topological and biological relevance with reference to the elite genes, attained from genecards. Finally, we discover that the genes F2RL3, APPL1, CALM1, IFNGR1, LPAR1, ANGPT2, ARPC2, CGN, CLDN7, ATP6V1C2, CEACAM1, FTL, PLAU,PSMB4, and EPHB2 carry both the topological and biological significance of previously established ESCC elite genes. Therefore, we declare the aforementioned genes as potential biomarkers of ESCC. [Display omitted] • EnsemBic exclusively comprises the high-quality biclusters obtained from the well-known base biclustering algorithms. • The biclusters extracted by EnsemBic undergo validation using prominent functional and biological measures, establishing their high functional and biological significance. • Topological analysis reveals the usefulness of extracted biclusters in identifying potential biomarkers of ESCC. • Validation through gene enrichment analysis and pathway exploration ensures the biological relevance and significance of the identified potential biomarkers. • A specialized literature survey substantiates the significance of the identified potential biomarkers responsible for ESCC. [ABSTRACT FROM AUTHOR]

Background: Cases of tuberculosis (TB) and multidrug-resistant TB (MDR-TB) in South-east Asia including Indonesia are still high. The presence of mixed infections in TB cases has been reported. Several studies revealed the role of the human microbiome in TB. This study purposes to characterize microbiome which can be a potential biomarker of chronicity in TB or MDR-TB. Methods: Sputum samples of pulmonary TB patients confirmed MDR-TB and resistant to rifampicin TB (RR-TB) were conducted Metagenomic next-generation sequencing. Principal coordinate analysis of UniFrac's showing the community structure of microbiome in MDR-TB comorbid diabetes mellitus (DM) is different from RR-TB noncomorbid DM (P = 0.003). Results: Proteobacteria microbiome in MDR-TB comorbid DM was more abundant than in RR-TB noncomorbid DM. Actinobacteria found in the small quantity in RR-TB and MDR-TB. Diversity of microbiome genera was greater in RR-TB. The linear discriminant analysis effect size analysis represents a genus biomarker whose abundance shows significant differences between groups, genus Rothia as a potential biomarker for RR-TB noncomorbid DM. Conclusions: Interesting findings is the community structure of microbiome in MDR-TB and RR-TB. In chronic TB such as recurrent, associated MDR-TB should attention to the findings of a small number of Actinobacteria could be a biomarker of TB which is also a determinant in patient taking combined anti-TB drugs of choice. [ABSTRACT FROM AUTHOR]

Fructus Psoraleae (FP) is commonly used in the treatment of vitiligo, osteoporosis, and other diseases in clinic. As a result, the toxicity caused by FP is frequently encountered in clinical practice; however, the underlying toxicity mechanism remains unclear. The purpose of this study was to investigate the toxic effect of the ethanol extract of FP (EEFP) in rats and to explore the underlying toxic mechanisms using a metabolomics approach. The toxicity was evaluated by hematological indicators, biochemical indicators, and histological changes. In addition, a serum metabolomic method based on ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight MS (UPLC–Q‐TOF–MS) had been established to investigate the hepatorenal toxicity of FP. Multivariate statistical approaches, such as partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis, were built to evaluate the toxic effects of FP and find potential biomarkers and metabolic pathways. Ten endogenous metabolites had been identified and the related metabolic pathways were involved in phospholipid metabolism, amino acid metabolism, purine metabolism, and antioxidant system activities. The results showed that long‐term exposure to high‐dose EEFP may cause hepatorenal toxicity in rats. Therefore, serum metabolomics can improve the diagnostic efficiency of FP toxicity and make it more accurate and comprehensive. [ABSTRACT FROM AUTHOR]

Objective · To identify some related molecular markers for the diagnosis and treatment of lung adenocarcinoma by transcriptome analysis. Methods · The differentially expressed analyses were performed to identify the differentially expressed genes (DEGs), the differentially expressed miRNAs (DEMs), and the differentially expressed circRNAs (DECs). Functional and pathway enrichment analyses were conducted for DEGs, and the targets prediction for DEMs. Regulated network of the DEGs and DEMs was constructed, and some candidates were selected. The biomarkers obtained were verified by the Cancer Genome Atlas (TCGA) database and the qRT-PCR, and the correlation between their expression levels and overall survival and tumor stage were analyzed. Results · Sixty-one overlaps were contained in the 3 sets of DEGs in 3 gene expression profiles, which were enriched in 32 gene ontology (GO) terms and 10 pathways. Twenty-four DEMs were identified, and 612 miRNA-target pairs were screened out that the target genes were DEGs. In the circRNA microarray, 92 DECs were obtained. ADRA1A, hsa-miR-141-5p and hsa-miR-191-3p were important nodes in the network. TCGA and qRT-PCR results were consistent with the microarray analysis results, in addition, hsa-miR-191-3p was significantly correlated with tumor stage. Conclusion · ADRA1A, hsa-miR-141-5p, hsa-miR-191-3p, SFTPC, ITLN2 and SLC6A4 might be potential biomarkers of lung adenocarcinoma, and hsa-miR-191-3p might be associated with tumor progression. [ABSTRACT FROM AUTHOR]

COVID-19 is a pandemic that began to spread worldwide caused by SARS-CoV-2. Lung cancer patients are more susceptible to SARS-CoV-2 infection. The SARS-CoV-2 enters into the host by the ACE2 receptor. Thus, ACE2 is the key to understand the mechanism of SARS-CoV-2 infection. However, the lack of knowledge about the biomarker of COVID-19 warrants the development of ACE2 biomarkers. The analysis of ACE2 expression in lung cancer was performed using The Cancer Genome Atlas (TCGA). Therefore, we investigated the prognosis, clinical characteristics, and mutational analysis of lung cancer. We also analyzed the shared proteins between the COVID-19 and lung cancer, protein-protein interactions, gene-miRNAs, gene-transcription factors (TFs), and the signaling pathway. Finally, we compared the mRNA expression of ACE2 and its co-expressed proteins using the TCGA. The up-regulation of ACE2 in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) was found irrespective of gender and age. We found the low survival rate in high expression of ACE2 in lung cancer patients and 16 mutational positions. The functional assessment of targeted 12,671, 3107, and 29 positive genes were found in COVID-19 disease, LUAD, and LUSC, respectively. Then, we identified eight common genes that interact with 20 genes, 219 miRNAs, and 16 TFs. The common genes performed the mRNA expression in lung cancer, which proved the ACE2 is the best potential biomarker compared to co-expressed genes. This study uncovers the relationship between COVID-19 disease and lung cancer. We identified ACE2 and also its co-expressed proteins are the potential biomarker and therapy as the current COVID-19 disease and lung cancer. Unlabelled Image • High transcriptional expression of ACE2 due to COVID-19 may result in poor lung cancer outcome. • The investigation of clinical profiles and mutational positions of ACE2 in lung cancer. • The gene ontologies and pathways of ACE2 and their co-expressed genes were identified. • The protein-protein, gene-miRNA, and gene-TF interactions were identified. • ACE2 and also its co-expressed proteins are the potential biomarker and therapy as the current COVID-19 disease and lung cancer. [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive type of skin cancer and has a high mortality rate once metastasis occurs. Hypoxia is a universal characteristic of the microenvironment of cancer and a driver of melanoma progression. In recent years, long noncoding RNAs (lncRNAs) have attracted widespread attention in oncology research. In this study, screening was performed and revealed seven hypoxia-related lncRNAs AC008687.3, AC009495.1, AC245128.3, AL512363.1, LINC00518, LINC02416 and MCCC1-AS1 as predictive biomarkers. A predictive risk model was constructed via univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Patients were grouped according to the model risk score, and Kaplan-Meier analysis was performed to compare survival between groups. Functional and pathway enrichment analyses were performed to compare gene set enrichment between groups. Moreover, a nomogram was constructed with the risk score as a variable. In both the training and validation sets, patients in the low-risk group had better overall survival than did those in the high-risk group (P<0.001). The 3-, 5- and 10-year area under the curve (AUC) values for the nomogram model were 0.821, 0.795 and 0.820, respectively. Analyses of immune checkpoints, immunotherapy response, drug sensitivity, and mutation landscape were also performed. The results suggested that the low-risk group had a better response to immunotherapeutic. In addition, the nomogram can effectively predict the prognosis and immunotherapy response of melanoma patients. The signature of seven hypoxia-related lncRNAs showed great potential value as an immunotherapy response biomarker, and these lncRNAs might be treatment targets for melanoma patients., Competing Interests: None., (AJCR Copyright © 2024.)

Small cell lung cancer (SCLC) is a highly lethal disease. Although radiation therapy is effective for the majority of patients with SCLC, patient sensitivity to radiation varies. The lack of biomarkers impedes advances in targeting radiation-sensitive patients. In this study, the changes in transcription patterns of SCLC cell lines were evaluated with or without 2 Gy gamma radiation. The results demonstrated that peptidyl-prolyl cis-trans isomerase A pseudogene 43 (PPIAP43) transcription was increased 2-fold in cells irradiated with 2 Gy gamma radiation compared with unirradiated cells in pre-reported radio-sensitive sensitive cell lines H69, H128, H146, H209 and H187. These cells shared 259 upregulated and 96 downregulated RNA transcripts following radiation. Pre-reported less sensitive cell lines H526, D53, D114 and D153 in which PPIAP43 was not upregulated 2-fold following irradiation with 2 Gy gamma radiation compared with unirradiated cells, shared 3 upregulated and 9 downregulated RNA transcripts. The RNA transcript of PPIAP43 was aligned with the mRNA of peptidyl-prolyl cis-trans isomerase A (PPIA) at 2 sections (3,732 to 3,917 and 5,327 to 5,657 of the PPIA gene) and the sequences were shown to be 96 and 94% similar, respectively. Therefore, PPIAP43 may act as a sponge for microRNAs which bind with the RNA of PPIA. Therefore, PPIAP43 RNA transcription may serve as a potential biomarker of radio-sensitivity of SCLC. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is malignant tumor with abnormal proliferation of bone marrow plasma cells. The existing clinical tools used to determine treatment response and tumor relapse are limited in sensitivity. We investigated the CD138+ microparticles (MPs) of MM patients to find out whether MPs could provide a novel means to monitor the malignant cells in MM patients. Our study showed that the levels of MPs were significantly elevated in MM patients. The MP counts in peripheral blood from new diagnosed MM patients were significantly higher than patients in CR and HD. Consist with the total MPs, the number of the PC-derived MPs (CD138+) increased in BM from MM patients compared with CR and HD. The ratio of the PC-derived MPs (CD138+) in BM increased in MM patients compared with CR and HD. The correlation test revealed that the CD138+ MPs in BM and PB were all positively correlated with the plasmacyte ratio in bone marrow (BMPC) and the β2 -MG. New diagnosed MM patients and controls were compared, and ROC curves were used to identify cutoff points with optimal sensitivity and specificity concerning the ratios and counts of CD138+ MPs in BM and PB. The AUC of the CD138+ MP counts in BM was 0.767, and in PB was 0.680. The AUC of the CD138+ MP ratios in BM was 0.714, and in PB was 0.666. According to this, the counts of CD138+ MPs in BM showed to be a powerful marker of diagnosis. We demonstrated that CD138+ MPs from the plasma provide support for a potential monitoring biomarker of MM. [ABSTRACT FROM AUTHOR]

Neurosyphilis is a chronic central nervous system infectious disease caused by Treponema pallidum. Our aim was to study the metabolic profiling in the cerebrospinal fluid of neurosyphilis patients and identify specific potential biomarkers. Fifteen cerebrospinal fluid samples from neurosyphilis patients and 14 non-neurosyphilis samples were analyzed by liquid chromatography–mass spectrometer (LC–MS). The LC–MS data were preprocessed by supervised pattern recognition to obtain diagnostic models. Both orthogonal projections to a latent structures discriminant analysis (OPLS-DA) and a t test were used to obtain specific metabolites for neurosyphilis. LC–MS data showed that the metabolites in cerebrospinal fluid (CSF) from neurosyphilis are different from the non-neurosyphilis group. The OPLS-DA model parameters R2Y and Q2Y are both more than 0.7 and indicated a satisfactory diagnostic performance. Bilirubin, l-histidine, prostaglandin E2, alpha-kamlolenic acid, and butyryl-l-carnitine and palmitoyl-l-carnitine were identified as novel potential biomarkers for neurosyphilis. The metabolic study of CSF may provide a new way to explore the pathogenesis of neurosyphilis. [ABSTRACT FROM AUTHOR]