[Update on lupus nephritis]. / Update Lupusnephritis.

In addition to the butterfly rash, lupus nephritis is the most specific manifestation of systemic lupus erythematosus (SLE). The perspective on this organ manifestation has fundamentally changed as well as the manifestation of SLE itself 40 years after the first multicenter clinical study on lupus nephritis. Even if there is a faint glimpse of hope of a cure, there is still the fight against the problem of nonresponders and also the progressive loss of organ function. This update gives an overview of the current importance of lupus nephritis in the context of the whole SLE disease, of the special features and on the options provided by the new diagnostic and therapeutic developments.

The Link Between Matrix Metalloproteinases and Alzheimer's Disease Pathophysiology.

Alzheimer's disease (AD) is a major contributor to dementia and the most common neurodegenerative disorder. In AD pathophysiology, matrix metalloproteinases (MMPs)-proteolytic enzymes, best known to be responsible for remodeling and degradation of the extracellular matrix-were suggested to play an important role. Due to the diverse nature of the published data and frequent inconsistent results presented in available papers, it was considered essential to analyze all aspects of MMP literature with respect to AD pathophysiology and attempt to outline a unifying concept for understanding their role in AD. Thus, the main contribution of this review article is to summarize the most recent research on the participation of MMP in AD pathophysiology obtained using the cell cultures to understand the molecular principles of their action. Furthermore, an updated comprehensive view regarding this topic based exclusively on papers from human studies is provided as well. It can be concluded that determining the exact role of any particular MMPs in the AD pathophysiology holds promise for establishing their role as potential biomarkers reflecting the severity or progression of this disease or for developing new therapeutic agents targeting the processes that lead to AD.

Ecotoxicological effects of tungsten on celery (Apium graveolens L) and pepper (Capsicum spp.).

Background: Tungsten (W) is an emerging heavy metal pollutant, yet research remains scarce on the biomonitor and sensitive biomarkers for W contamination. Methods: In this study, celery and pepper were chosen as study subjects and subjected to exposure cultivation in solutions with five different levels of W. The physiological and biochemical toxicities of W on these two plants were systematically analyzed. The feasibility of utilizing celery and pepper as biomonitor organisms for W contamination was explored and indicative biomarkers were screened. Results: The results indicated that W could inhibit plants' root length, shoot height, and fresh weight while concurrently promoting membrane lipid peroxidation. Additionally, W enhanced the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and total antioxidant capacity (TAOC) to counteract oxidative damage. From a physiological perspective, pepper exhibited potential as a biomonitor for W contamination. Biochemical indicators suggested that SOD could serve as a sensitive biomarker for W in celery, while TAOC and POD were more suitable for the roots and leaves of pepper. In conclusion, our study investigated the toxic effects of W on celery and pepper, contributing to the understanding of W's environmental toxicity. Furthermore, it provided insights for selecting biomonitor organisms and sensitive biomarkers for W contamination.

Circulating miRNA profiles and the risk of hemorrhagic transformation after thrombolytic treatment of acute ischemic stroke: a pilot study.

Background: Hemorrhagic transformation (HT) in acute ischemic stroke is likely to occur in patients treated with intravenous thrombolysis (IVT) and may lead to neurological deterioration and symptomatic intracranial hemorrhage (sICH). Despite the complex inclusion and exclusion criteria for IVT and some useful tools to stratify HT risk, sICH still occurs in approximately 6% of patients because some of the risk factors for this complication remain unknown. Objective: This study aimed to explore whether there are any differences in circulating microRNA (miRNA) profiles between patients who develop HT after thrombolysis and those who do not. Methods: Using qPCR, we quantified the expression of 84 miRNAs in plasma samples collected prior to thrombolytic treatment from 10 individuals who eventually developed HT and 10 patients who did not. For miRNAs that were downregulated (fold change (FC) <0.67) or upregulated (FC >1.5) with p < 0.10, we investigated the tissue specificity and performed KEGG pathway annotation using bioinformatics tools. Owing to the small patient sample size, instead of multivariate analysis with all major known HT risk factors, we matched the results with the admission NIHSS scores only. Results: We observed trends towards downregulation of miR-1-3p, miR-133a-3p, miR-133b and miR-376c-3p, and upregulation of miR-7-5p, miR-17-3p, and miR-296-5p. Previously, the upregulated miR-7-5p was found to be highly expressed in the brain, whereas miR-1, miR-133a-3p and miR-133b appeared to be specific to the muscles and myocardium. Conclusion: miRNA profiles tend to differ between patients who develop HT and those who do not, suggesting that miRNA profiling, likely in association with other omics approaches, may increase the current power of tools predicting thrombolysis-associated sICH in acute ischemic stroke patients. This study represents a free hypothesis-approach pilot study as a continuation from our previous work. Herein, we showed that applying mathematical analyses to extract information from raw big data may result in the identification of new pathophysiological pathways and may complete standard design works.

ISG15 mediates the function of extracellular vesicles in promoting ovarian cancer progression and metastasis.

The interferon stimulated gene 15 (ISG15), a ubiquitin like protein and its conjugates have been implicated in various human malignancies. However, its role in ovarian cancer progression and metastasis is largely unknown. In high grade serous ovarian cancer (HGSOC), ascites is the major contributor to peritoneal metastasis. In this study, we identified significantly elevated ISG15 protein expression in HGSOC patient ascites, ascites derived primary ovarian cancer cells (POCCs), POCC small extracellular vesicles (sEVs) as well as metastatic tissue. Our results demonstrates that ISG15 increases exocytosis in ascites-derived POCCs by decreasing the endosome-lysosomal fusion, indicating a key role in sEV secretion. Further, knockdown (KD) of ISG15 resulted in a significant decrease in vesicles secretion from HGSOC cells and in vivo mouse models, leading to reduced HGSOC cell migration and invasion. Furthermore, our pre-clinical mouse model studies revealed the influence of vesicular ISG15 on disease progression and metastasis. In addition, knockdown of ISG15 or using the ISG15 inhibitor, DAP5, in combination therapy with carboplatin showed to improve the platinum sensitivity in-vitro and reduce tumour burden in-vivo. We also found that ISG15 expression within sEV represents a promising prognostic marker for HGSOC patients. Our findings suggest that ISG15 is a potential therapeutic target for inhibiting progression and metastasis in HGSOC and that vesicular ISG15 expression could be a promising biomarker in the clinical management of ovarian cancer. Significance: High-grade serous ovarian cancer (HGSOC) has high morbidity and mortality rates, but its progression and metastasis are still poorly understood, and there is an urgent need for early detection and targeted therapies. Our study presents novel findings that implicate ISG15-mediated vesicular proteins in the advancement and spread of HGSOC. These results offer pre-clinical evidence of potential new molecular targets, prognostic markers and therapeutic strategies for HGSOC that could ultimately enhance patient survival.

The novel m6A writer methyltransferase 5 is a promising prognostic biomarker and associated with immune cell infiltration in oral squamous cell carcinoma.

BACKGROUND: Emerging research has identified the N6-methyladenosine (m6A) modification and its regulatory enzymes, including methyltransferase 5 (METTL5), as critical players in cancer biology. However, the role of METTL5 in oral squamous cell carcinoma (OSCC) remains poorly understood. MATERIALS AND METHODS: We conducted a comprehensive study to investigate the expression and implications of METTL5 in OSCC. We recruited 76 OSCC patients to analyze METTL5 mRNA and protein expression using RT-qPCR and western blot. Additionally, we analyzed METTL5 expression and its correlation with clinical features, patient prognosis, immune cell infiltration, and biological pathways using the TCGA-HNSCC dataset, which primarily consists of OSCC samples. RESULTS: Our findings revealed significant overexpression of METTL5 in OSCC tissues compared to normal tissues. The high expression of METTL5 is associated with advanced cancer stages, higher tumor grades, nodal metastasis, and poorer patient outcomes, indicating its involvement in cancer progression. In silico functional analysis revealed that METTL5 plays a role in multiple biological pathways, highlighting its importance in cancer biology. Moreover, METTL5 has complex relationships with immune regulatory genes, suggesting its potential role in shaping the tumor immune microenvironment. CONCLUSION: METTL5 is a promising candidate for the prognosis and therapeutic intervention of OSCC. Its overexpression in cancer tissues, association with clinical features, and intricate links to immune regulatory networks underscore its significance in this malignancy. This study contributes to a deeper understanding of the complex factors influencing OSCC, and provides a foundation for future research and potential clinical applications.

Dissecting Crucial Gene Markers Involved in HPV-Associated Oropharyngeal Squamous Cell Carcinoma from RNA-Sequencing Data through Explainable Artificial Intelligence.

BACKGROUND: The incidence rate of oropharyngeal squamous cell carcinoma (OPSCC) worldwide is alarming. In the clinical community, there is a pressing necessity to comprehend the etiology of the OPSCC to facilitate the administration of effective treatments. METHODS: This study confers an integrative genomics approach for identifying key oncogenic drivers involved in the OPSCC pathogenesis. The dataset contains RNA-Sequencing (RNA-Seq) samples of 46 Human papillomavirus-positive head and neck squamous cell carcinoma and 25 normal Uvulopalatopharyngoplasty cases. The differential marker selection is performed between the groups with a log2FoldChange (FC) score of 2, adjusted p-value < 0.01, and screened 714 genes. The Particle Swarm Optimization (PSO) algorithm selects the candidate gene subset, reducing the size to 73. The state-of-the-art machine learning algorithms are trained with the differentially expressed genes and candidate subsets of PSO. RESULTS: The analysis of predictive models using Shapley Additive exPlanations revealed that seven genes significantly contribute to the model's performance. These include ECT2, LAMC2, and DSG2, which predominantly influence differentiating between sample groups. They were followed in importance by FAT1, PLOD2, COL1A1, and PLAU. The Random Forest and Bayes Net algorithms also achieved perfect validation scores when using PSO features. Furthermore, gene set enrichment analysis, protein-protein interactions, and disease ontology mining revealed a significant association between these genes and the target condition. As indicated by Shapley Additive exPlanations (SHAPs), the survival analysis of three key genes unveiled strong over-expression in the samples from "The Cancer Genome Atlas". CONCLUSIONS: Our findings elucidate critical oncogenic drivers in OPSCC, offering vital insights for developing targeted therapies and enhancing understanding its pathogenesis.

Exploring the Neuroinflammatory Pathway in Epilepsy and Cognitive Impairment: Role of HMGB1 and Translational Challenges.

Neuroinflammation has emerged as a shared molecular mechanism in epilepsy and cognitive impairment, offering new insights into the complex interplay between immune responses and brain function. Evidence reveals involvement of High mobility group box 1 (HMGB1) in blood-brain barrier disruption and correlations with epilepsy severity and drug resistance. While anti-inflammatory treatments show promise, translating these discoveries faces challenges in elucidating mechanisms and developing reliable biomarkers. However, strategically targeting neuroinflammation and HMGB1-mediated inflammation holds therapeutic potential. This review synthesises knowledge on HMGB1 and related biomarkers in epilepsy and cognitive impairment to shape future research and treatments targeting these intricate inflammatory processes.

Systematic Review and Metanalysis of the Expression of Blood-Based and Cerebrospinal Fluid-Based Biomarkers Related to Inflammatory Mediators in Neuropathic Pain.

BACKGROUND: The understanding of neuropathic pain remains incomplete, highlighting the need for research on biomarkers for improved diagnosis and treatment. This review focuses on identifying potential biomarkers in blood and cerebrospinal fluid for neuropathic pain in different neuropathies. METHODS: Searches were performed in six databases: PubMed, Web of Science, Scopus, Cochrane Library, EMBASE, and CINAHL. Included were observational studies, namely cross-sectional, cohort, and case-control, that evaluated quantitative biomarkers in blood or cerebrospinal fluid. Data were qualitatively synthesized, and meta-analyses were conducted using R. The study is registered with PROSPERO under the ID CRD42022323769. RESULTS: The literature search resulted in 16 studies for qualitative and 12 for quantitative analysis, covering patients over 18 years of age with painful neuropathies. A total of 1403 subjects were analyzed, identifying no significant differences in levels of C-Reactive Protein (CRP), Interleukin-6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-alpha) between patients with and without pain. Despite the high inter-rater reliability and adequate bias assessment, the results suggest negligible differences in inflammatory biomarkers, with noted publication bias and heterogeneity among studies, indicating the need for further research. CONCLUSIONS: Our review underscores the complex nature of neuropathic pain and the challenges in identifying biomarkers, with no significant differences found in CRP, IL-6, and TNF-alpha levels between patients with and without pain. Despite methodological robustness, the results are limited by publication bias and heterogeneity. This emphasizes the need for further research to discover definitive biomarkers for improved diagnosis and personalized treatment of neuropathic pain.

Plasma amyloid beta X-42/X-40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease.

INTRODUCTION: Blood-based biomarkers are a cost-effective and minimally invasive method for diagnosing the early and preclinical stages of amyloid positivity (AP). Our study aims to investigate our novel immunoprecipitation-immunoassay (IP-IA) as a test for predicting cognitive decline. METHODS: We measured levels of amyloid beta (Aß)X-40 and AßX-42 in immunoprecipitated eluates from the DELCODE cohort. Receiver-operating characteristic (ROC) curves, regression analyses, and Cox proportional hazard regression models were constructed to predict AP by Aß42/40 classification in cerebrospinal fluid (CSF) and conversion to mild cognitive impairment (MCI) or dementia. RESULTS: We detected a significant correlation between AßX-42/X-40 in plasma and CSF (r = 0.473). Mixed-modeling analysis revealed a substantial prediction of AßX-42/X-40 with an area under the curve (AUC) of 0.81 for AP (sensitivity: 0.79, specificity: 0.74, positive predictive value [PPV]: 0.71, negative predictive value [NPV]: 0.81). In addition, lower AßX-42/X-40 ratios were associated with negative PACC5 slopes, suggesting cognitive decline. DISCUSSION: Our results suggest that assessing the plasma AßX-42/X-40 ratio via our semiautomated IP-IA is a promising biomarker when examining patients with early or preclinical AD. HIGHLIGHTS: New plasma Aß42/Aß40 measurement using immunoprecipitation-immunoassay Plasma Aß42/Aß40 associated with longitudinal cognitive decline Promising biomarker to detect subjective cognitive decline at-risk for brain amyloid positivity.

Roles of long non­coding RNA SNHG16 in human digestive system cancer (Review).

The incidence of tumors in the human digestive system is relatively high, including esophageal cancer, liver cancer, pancreatic cancer, gastric cancer and colorectal cancer. These malignancies arise from a complex interplay of environmental and genetic factors. Among them, long non­coding RNAs (lncRNAs), which cannot be translated into proteins, serve an important role in the development, progression, migration and prognosis of tumors. Small nucleolar RNA host gene 16 (SNHG16) is a typical lncRNA, and its relationship with digestive system tumors has been widely explored. The prevailing hypothesis suggests that the principal molecular mechanism of SNHG16 in digestive system tumors involves it functioning as a competitive endogenous RNA that interacts with other proteins, regulates various genes and influences a downstream target molecule. The present review summarizes recent research on the relationship between SNHG16 and numerous types of digestive system cancer, encompassing its biological functions, underlying mechanisms and potential clinical implications. Furthermore, it outlines the association between SNHG16 expression and pertinent risk factors, such as smoking, infection and diet. The present review indicated the promise of SNHG16 as a potential biomarker and therapeutic target in human digestive system cancer.

The link between gut microbiome and Alzheimer's disease: From the perspective of new revised criteria for diagnosis and staging of Alzheimer's disease.

Over the past decades, accumulating evidence suggests that the gut microbiome exerts a key role in Alzheimer's disease (AD). The Alzheimer's Association Workgroup is updating the diagnostic criteria for AD, which changed the profiles and categorization of biomarkers from "AT(N)" to "ATNIVS." Previously, most of studies focus on the correlation between the gut microbiome and amyloid beta deposition ("A"), the initial AD pathological feature triggering the "downstream" tauopathy and neurodegeneration. However, limited research investigated the interactions between the gut microbiome and other AD pathogenesis ("TNIVS"). In this review, we summarize current findings of the gut microbial characteristics in the whole spectrum of AD. Then, we describe the association of the gut microbiome with updated biomarker categories of AD pathogenesis. In addition, we outline the gut microbiome-related therapeutic strategies for AD. Finally, we discuss current key issues of the gut microbiome research in the AD field and future research directions. HIGHLIGHTS: The new revised criteria for Alzheimer's disease (AD) proposed by the Alzheimer's Association Workgroup have updated the profiles and categorization of biomarkers from "AT(N)" to "ATNIVS." The associations of the gut microbiome with updated biomarker categories of AD pathogenesis are described. Current findings of the gut microbial characteristics in the whole spectrum of AD are summarized. Therapeutic strategies for AD based on the gut microbiome are proposed.

Microarray Chip-Based High-Throughput Screening of Neurofilament Light Chain Self-Assembling Peptide for Noninvasive Monitoring of Alzheimer's Disease.

Alzheimer's disease (AD) starts decades before cognitive symptoms develop. Easily accessible and cost-effective biomarkers that accurately reflect AD pathology are essential for both monitoring and therapeutics of AD. Neurofilament light chain (NfL) levels in blood and cerebrospinal fluid are increased in AD more than a decade before the expected onset, thus providing one of the most promising blood biomarkers for monitoring of AD. The clinical practice of employing single-molecule array (Simoa) technology for routine use in patient care is limited by the high costs. Herein, we developed a microarray chip-based high-throughput screening method and screened an attractive self-assembling peptide targeting NfL. Through directly "imprinting" and further analyzing the sequences, morphology, and affinity of the identified self-assembling peptides, the Pep-NfL peptide nanosheet with high binding affinity toward NfL (KD = 1.39 × 10-9 mol/L), high specificity, and low cost was characterized. The superior binding ability of Pep-NfL was confirmed in AD mouse models and cell lines. In the clinical setting, the Pep-NfL peptide nanosheets hold great potential for discriminating between patients with AD (P < 0.001, n = 37), mild cognitive impairment (P < 0.05, n = 26), and control groups (n = 30). This work provides a high-throughput, high-sensitivity, and economical system for noninvasive tracking of AD to monitor neurodegeneration at different stages of disease. The obtained Pep-NfL peptide nanosheet may be useful for assessing dynamic changes in plasma NfL concentrations to evaluate disease-modifying therapies as a surrogate end point of neurodegeneration in clinical trials.

Assessing short-term feed efficiency and its association with biological markers in herbage-fed dairy cows.

Feed efficiency is an important trait of dairy production. However, assessing feed efficiency is constrained by the associated cost and difficulty in measuring individual feed intake, especially on pastures. The objective of this study was to investigate short-term feed efficiency traits of herbage-fed dairy cows and screening of potential biomarkers (n = 238). Derived feed efficiency traits were ratio-based (i.e., feed conversion ratio (FCR) and N use efficiency (NUE)) or residual-based (i.e., residual feed intake (RFI), residual energy intake (REI), and residual N intake (RNI)). Thirty-eight Holstein and 16 Swiss Fleckvieh dairy cows underwent a 7-d measurement period during mid- and/or late-lactation. The experimental data (n = 100 measurement points) covered different lactational and herbage-fed system situations: mid-lactation grazing (n = 56), late-lactation grazing (n = 28), and late-lactation barn feeding (n = 16). During each measuring period, the individual herbage intake of each cow was estimated using the n-alkane marker technique. For each cow, biomarkers representing milk constituents (n = 109), animal characteristics (n = 13), behaviour, and activity (n = 46), breath emissions (n = 3), blood constituents (n = 35), surface, and rectal temperature (n = 29), hair cortisol (n = 1), and near-infrared (NIR) spectra of faeces and milk (n = 2) were obtained. The relationships between biomarkers and efficiency traits were statistically analysed with univariate linear regression and for NIR spectra using partial least squares regression with feed efficiency traits. The feed efficiency traits were interrelated with each other (r: -0.57 to -0.86 and 0.49-0.81). The biomarkers showed varying R2 values in explaining the variability of feed efficiency traits (FCR: 0.00-0.66, NUE: 0.00-0.74, RFI: 0.00-0.56, REI: 0.00-0.69, RNI: 0.00-0.89). Overall, the feed efficiency traits were best explained by NIR spectral characteristics of milk and faeces (R2: 0.25-0.89). Biomarkers show potential for predicting feed efficiency in herbage-fed dairy cows. NIR spectra data analysis of milk and faeces presents a promising method for estimating individual feed efficiency upon further validation of prediction models. Future applications will depend on the ability to improve the robustness of biomarkers to predict feed efficiency in a greater variety of environments (locations), managing conditions, feeding systems, production intensities, and other aspects.

A universal urinary cell gene signature of acute rejection in kidney allografts.

INTRODUCTION: Acute rejection (AR) undermines the life-extending benefits of kidney transplantation and is diagnosed using the invasive biopsy procedure. T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), or concurrent TCMR + ABMR (Mixed Rejection [MR]) are the three major types of AR. Development of noninvasive biomarkers diagnostic of AR due to any of the three types is a useful addition to the diagnostic armamentarium. METHODS: We developed customized RT-qPCR assays and measured urinary cell mRNA copy numbers in 145 biopsy-matched urine samples from 126 kidney allograft recipients. We determined whether the urinary cell three-gene signature diagnostic of TCMR (Suthanthiran et al., 2013) discriminates patients with no rejection biopsies (NR, n = 50) from those with ABMR (n = 28) or MR (n = 20) biopsies. RESULTS: The urinary cell three-gene signature discriminated all three types of rejection biopsies from NR biopsies (P < 0.0001, One-way ANOVA). Dunnett's multiple comparisons test yielded P < 0.0001 for NR vs. TCMR; P < 0.001 for NR vs. ABMR; and P < 0.0001 for NR vs. MR. By bootstrap resampling, optimism-corrected area under the receiver operating characteristic curve (AUC) was 0.749 (bias-corrected 95% confidence interval [CI], 0.638 to 0.840) for NR vs. TCMR (P < 0.0001); 0.780 (95% CI, 0.656 to 0.878) for NR vs. ABMR (P < 0.0001); and 0.857 (95% CI, 0.727 to 0.947) for NR vs. MR (P < 0.0001). All three rejection categories were distinguished from NR biopsies with similar accuracy (all AUC comparisons P > 0.05). CONCLUSION: The urinary cell three-gene signature score discriminates AR due to TCMR, ABMR or MR from NR biopsies in human kidney allograft recipients.

Mass spectrometry imaging in pulmonary disorders.

Mass Spectrometry Imaging (MSI) represents a novel and advancing technology that offers unparalleled in situ characterization of tissues. It provides comprehensive insights into the chemical structures, relative abundances, and spatial distributions of a vast array of both identified and unidentified endogenous and exogenous compounds, a capability not paralleled by existing analytical methodologies. Recent scholarly endeavors have increasingly explored the utility of MSI in the adjunct diagnosis and biomarker research of pulmonary disorders, including but not limited to lung cancer. Concurrently, MSI has proven instrumental in elucidating the spatiotemporal dynamics of various pharmacological agents. This review concisely delineates the fundamental principles underpinning MSI, its applications in pulmonary disease diagnosis, biomarker discovery, and drug distribution investigations. Additionally, it presents a forward-looking perspective on the prospective trajectories of MSI technological advancements.

Contact System Activation and Bradykinin Generation in Angioedema: Laboratory Assessment and Biomarker Utilization.

The role of contact system activation has been clearly established in the pathogenesis of hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH). C1 inhibitor (C1INH)-protease complexes, levels of functional C1INH, plasma kallikrein activation, and cleavage of high-molecular-weight kininogen have each been associated with disease activity. More recently, HAE with normal levels of C1INH (HAE-nl-C1INH) has been recognized. Six genetic mutations have been identified which are linked to HAE-nl-C1INH phenotypes. The majority of individuals with HAE-nl-C1INH fall into the unknown category. There is substantial evidence that bradykinin generation underlies the recurrent attacks of swelling in some of these cohorts.

CTHRC1 is a prognostic biomarker correlated with immune infiltration in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, characterized by high morbidity, high mortality, and poor prognosis. Collagen triple helix repeat containing 1 (CTHRC1) has been shown to be highly expressed in various cancers. However, its biological functions, potential role as a biomarker, and its relationship with immune infiltrates in HNSCC remain unclear. Our principal objective was to analyze CTHRC1 expression, its prognostic implications, biological functions, and its effects on the immune system in HNSCC patients using bioinformatics analysis. METHODS: The expression matrix was obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). CTHRC1 expression in HNSCC was analyzed between tumor and adjacent normal tissues, different stages were compared, and its impact on clinical prognosis was assessed using Kaplan-Meier analysis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Variation Analysis (GSVA) were employed for enrichment analysis. The Search Tool for the Retrieval of Interacting Genes database (STRING) was used to analyze protein-protein interactions. Pearson correlation tests were used to investigate the association between CTHRC1 expression and immune checkpoints. The correlation between CTHRC1 and immune infiltration was investigated using CIBERSORT, TIMER, and ESTIMATE. RESULTS: Compared to adjacent normal tissues, CTHRC1 was found to be highly overexpressed in tumors. Increased expression of CTHRC1 was more evident in the advanced stage of HNSCC and predicted a poor prognosis. Most genes related to CTHRC1 in HNSCC were enriched in physiological functions of Extracellular matrix(ECM) and tumor. Furthermore, several immune checkpoints, such as TNFSF4 and CD276 have been shown to be associated with CTHRC1 expression. Notably, the level of CTHRC1 expression correlated significantly with immune infiltration levels, particularly activated macrophages in HNSCC. CONCLUSIONS: High expression of CTHRC1 predicts poor prognosis and is associated with immune infiltration in HNSCC, confirming its utility as a tumor marker for HNSCC. TRIAL REGISTRATION: Not applicable. All data are from public databases and do not contain any clinical trials.

Pan-cancer multi-omics analysis of PTBP1 reveals it as an inflammatory, progressive and prognostic marker in glioma.

PTBP1 is an oncogene that regulates the splicing of precursor mRNA. However, the relationship between PTBP1 expression and gene methylation, cancer prognosis, and tumor microenvironment remains unclear. The expression profiles of PTBP1 across various cancers were derived from the TCGA, as well as the GTEx and CGGA databases. The CGGA mRNA_325, CGGA mRNA_301, and CGGA mRNA_693 datasets were utilized as validation cohorts. Immune cell infiltration scores were approximated using the TIMER 2.0 tool. Functional enrichment analysis for groups with high and low PTBP1 expression was conducted using Gene Set Enrichment Analysis (GSEA). Methylation data were predominantly sourced from the SMART and Mexpress databases. Linked-omics analysis was employed to perform functional enrichment analysis of genes related to PTBP1 methylation, as well as to conduct protein functional enrichment analysis. Single-cell transcriptome analysis and spatial transcriptome analysis were carried out using Seurat version 4.10. Compared to normal tissues, PTBP1 is significantly overexpressed and hypomethylated in various cancers. It is implicated in prognosis, immune cell infiltration, immune checkpoint expression, genomic variation, tumor neoantigen load, and tumor mutational burden across a spectrum of cancers, with particularly notable effects in low-grade gliomas. In the context of gliomas, PTBP1 expression correlates with WHO grade and IDH1 mutation status. PTBP1 expression and methylation play an important role in a variety of cancers. PTBP1 can be used as a marker of inflammation, progression and prognosis in gliomas.

Challenges and Advances in Biomarker Detection for Rapid and Accurate Sepsis Diagnosis: An Electrochemical Approach.

Sepsis is a life-threatening condition with high mortality rates due to delayed treatment of patients. The conventional methodology for blood diagnosis takes several hours, which suspends treatment, limits early drug administration, and affects the patient's recovery. Thus, rapid, accurate, bedside (onsite), economical, and reliable sepsis biomarker reading of the clinical sample is an emergent need for patient lifesaving. Electrochemical label-free biosensors are specific and rapid devices that are able to perform analysis at the patient's bedside; thus, they are considered an attractive methodology in a clinical setting. To reveal their full diagnostic potential, electrode architecture strategies of fabrication are highly desirable, particularly those able to preserve specific antibody-antigen attraction, restrict non-specific adsorption, and exhibit high sensitivity with a low detection limit for a target biomarker. The aim of this review is to provide state-of-the-art methodologies allowing the fabrication of ultrasensitive and highly selective electrochemical sensors for sepsis biomarkers. This review focuses on different methods of label-free biomarker sensors and discusses their advantages and disadvantages. Then, it highlights effective ways of avoiding false results and the role of molecular labels and functionalization. Recent literature on electrode materials and antibody grafting strategies is discussed, and the most efficient methodology for overcoming the non-specific attraction issues is listed. Finally, we discuss the existing electrode architecture for specific biomarker readers and promising tactics for achieving quick and low detection limits for sepsis biomarkers.