Diagnostic Biomarker In Patients Research Articles

UL16‑binding protein 1 is a significant prognostic and diagnostic marker for breast cancer.

The aim of the present study was to investigate the association between UL16 binding protein 1 (ULBP1) and the prognosis of patients with and immune cell infiltration in breast cancer (BRCA). The mRNA data of BRCA and immune-related genes were extracted from The Cancer Genome Atlas and were analyzed using bioinformatics tools. Subsequently, the results obtained by bioinformatics were validated through the collection of clinical patient data at the Zibo Central hospital (Zibo, China). The difference in the expression of the ULBP1 gene between BRCA tissues and normal precancerous tissues was analyzed, followed by validation using immunohistochemistry. By combining clinical data from patients with BRCA, the prognostic and diagnostic significance of the ULBP1 gene in patients with BRCA was analyzed. Gene enrichment analysis was conducted to gain insight into the molecular mechanisms underlying the regulatory role of ULBP1 in BRCA by analyzing its related functions and signaling pathways. Furthermore, single sample gene set enrichment analysis (ssGSEA) and Spearman's correlation analysis were performed to explore the correlation between ULBP1 as a target gene related with tumor immune cell infiltration. The data revealed that ULBP1 is a target gene associated with immunity and the prognosis of patients with BRCA. Patients with BRCA with a high expression of ULBP1 had a poorer prognosis. ULBP1 expression correlated with progesterone receptor expression, estrogen receptor expression and histological type in patients with BRCA; thus, it may serve as an independent predictor for the overall survival rate of patients. Functional enrichment analysis revealed a significant co-expression between ULBP1 and ULBP2, ULBP3, retinoic acid early transcript 1K, as well as a significant enrichment of pathways associated with carcinogenesis and immune suppression. ssGSEA and Spearman's correlation analysis demonstrated significant correlations between ULBP1 expression and tumor immune cells, as well as immune checkpoints. Overall, the present study demonstrated that ULBP1 was associated with BRCA immunity and might serve as a prognostic and diagnostic biomarker for patients with BRCA. In addition, it might also be a potential target for the immunotherapy of BRCA.

Autism spectrum disorder: difficulties in diagnosis and microRNA biomarkers.

We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023, of which 4 studies were performed with whole blood, 4 with blood plasma, 5 with blood serum, 1 with serum neural cell adhesion molecule L1-captured extracellular vesicles, 1 with blood cells, and 2 with peripheral blood mononuclear cells. Most of the studies involved children and the study cohorts were largely males. Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression. Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls. The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p, -197-5p, -424-5p, -664a-3p, -365a-3p, -619-5p, -664a- 3p, -3135a, -328-3p, and -500a-5p in blood plasma and miR-151a-3p, -181b-5p, -320a, -328, -433, -489, -572, -663a, -101-3p, -106b-5p, -19b-3p, -195-5p, and -130a-3p in blood serum of children, and miR-15b-5p and -6126 in whole blood of adults. Several important limitations were identified in the studies reviewed, and need to be taken into account in future studies. Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.

Expression Analysis of Circulating microRNAs in Saliva and Plasma for the Identification of Clinically Relevant Biomarkers for Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders.

This study aims to evaluate the expression of salivary and plasmatic miRNAs as diagnostic biomarkers in patients with oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). A total of 25 patients were divided into three groups, according to their diagnosis: OSCC patients (n = 14); OPMDs patients (n = 6); and healthy controls (n = 5). At the time at diagnosis/enrolment, patients underwent salivary and plasmatic collection. The expression of miRNA -21, -31, -138, -145, -184, and -424 were evaluated by real-time PCR. An F-test and ANOVA test were performed to evaluate the miRNA levels (significance at p < 0.05). By comparing miRNA expression levels from saliva, a statistically significant difference emerged in the expression of miR-138 and miR-424 between the three groups (p < 0.05). In particular, these two miRNAs showed decreased expression levels in saliva samples from OSCC and OPMD patients compared to those from healthy controls. On the other hand, miRNA expression levels in plasma were low in all the groups, and no statistically significant differences were found. Overall, our results showed that liquid biopsy from saliva may be a useful tool for the identification of diagnostic molecular biomarkers in OSCC and OPMDs.

The Association between Long Non-Coding RNAs and Alzheimer's Disease.

Neurodegeneration occurs naturally as humans age, but the presence of additional pathogenic mechanisms yields harmful and consequential effects on the brain. Alzheimer's disease (AD), the most common form of dementia, is a composite of such factors. Despite extensive research to identify the exact causes of AD, therapeutic approaches for treating the disease continue to be ineffective, indicating important gaps in our understanding of disease mechanisms. Long non-coding RNAs (lncRNAs) are an endogenous class of regulatory RNA transcripts longer than 200 nucleotides, involved in various regulatory networks, whose dysregulation is evident in several neural and extraneural diseases. LncRNAs are ubiquitously expressed across all tissues with a wide range of functions, including controlling cell differentiation and development, responding to environmental stimuli, and other physiological processes. Several lncRNAs have been identified as potential contributors in worsening neurodegeneration due to altered regulation during abnormal pathological conditions. Within neurological disease, lncRNAs are prime candidates for use as biomarkers and pharmacological targets. Gender-associated lncRNA expression is altered in a gender-dependent manner for AD, suggesting more research needs to be focused on this relationship. Overall, research on lncRNAs and their connection to neurodegenerative disease is growing exponentially, as commercial enterprises are already designing and employing RNA therapeutics. In this review we offer a comprehensive overview of the current state of knowledge on the role of lncRNAs in AD and discuss the potential implications of lncRNA as potential therapeutic targets and diagnostic biomarkers in patients with Alzheimer's disease.

LncRNA NEAT1 and miRNA 101 as potential diagnostic biomarkers in patients with alopecia areata

BackgroundAlopecia areata (AA) commonly displays as non-scarring, irregular hair loss. Experimental and clinical research have specifically implicated autoimmunity and genetics in the disruption of anagen hair follicles. AA patients' scalp lesions and peripheral blood mononuclear cells (PBMCs) exhibited an immune state imbalance. Numerous studies attempt to establish a connection between the occurrence and prognosis of AA and the epigenetic modulation of gene expression by long noncoding RNA (lncRNA) and microRNA (miRNA). The current study aimed to examine the serum levels of nuclear enriched abundant transcript 1 (NEAT1) and its target miRNA101 (miR-101) in AA and investigate the ability to use them as diagnostic biomarkers in the disease. MethodsSeventy-two AA patients were included in this prospective cohort study. Demographics, patient history, laboratory characteristics, and treatments were recorded. The miR-101 and NEAT1 levels were evaluated. ResultsSerum NEAT1 levels were lower in AA patients, but there was no significant difference. However, there was no substantial disparity in NEAT1 level regarding other disease characteristics. There was a substantial positive association between NEAT1 and miR-101 levels among cases. On the other hand, the results showed a markedly low mean of miR-101 levels among patients, but the miR-101 marker shows no significant difference regarding different disease characteristics. The specificity and sensitivity test for the miR-101 marker shows a significant specificity of 60 % and sensitivity of 75 % with a p-value of 0.001 and a cut-off value of 0.897. ConclusionsThe current research determined that miR-101 works as a diagnostic biomarker for AA.

Disulfidptosis-related Protein RPN1 may be a Novel Anti-osteoporosis Target of Kaempferol.

Osteoporosis (OP) is an age-related skeletal disease. Kaempferol can regulate bone mesenchymal stem cells (BMSCs) osteogenesis to improve OP, but its mechanism related to disulfidptosis, a newly discovered cell death mechanism, remains unclear. The study aimed to investigate the biological function and immune mechanism of disulfidptosis- related ribophorin I (RPN1) in OP and to experimentally confirm that RPN1 is the target for the treatment of OP with kaempferol. Differential expression analysis was conducted on disulfide-related genes extracted from the GSE56815 and GSE7158 datasets. Four machine learning algorithms identified disease signature genes, with RPN1 identified as a significant risk factor for OP through the nomogram. Validation of RPN1 differential expression in OP patients was performed using the GSE56116 dataset. The impact of RPN1 on immune alterations and biological processes was explored. Predictive ceRNA regulatory networks associated with RPN1 were generated via miRanda, miRDB, and TargetScan databases. Molecular docking estimated the binding model between kaempferol and RPN1. The targeting mechanism of kaempferol on RPN1 was confirmed through pathological HE staining and immunohistochemistry in ovariectomized (OVX) rats. RPN1 was abnormally overexpressed in the OP cohort, associated with TNF signaling, hematopoietic cell lineage, and NF-kappa B pathway. Immune infiltration analysis showed a positive correlation between RPN1 expression and CD8+ T cells and resting NK cells, while a negative correlation with CD4+ naive T cells, macrophage M1, T cell gamma delta, T cell follicular helper cells, activated mast cells, NK cells, and dendritic cells, was found. Four miRNAs and 17 lncRNAs associated with RPN1 were identified. Kaempferol exhibited high binding affinity (-7.2 kcal/mol) and good stability towards the RPN1. The experimental results verified that kaempferol could improve bone microstructure destruction and reverse the abnormally high expression of RPN1 in the femur of ovariectomized rats. RPN1 may be a new diagnostic biomarker in patients with OP, and may serve as a new target for kaempferol to improve OP.

Diagnostic and Prognostic Value of miR-451 Expression in Colorectal Cancer: A Meta-Analysis.

The miR-451 has been reported to play an important role in colorectal cancer (CRC) pathogenesis and can be a pivotal diagnosis biomarker of CRC. Given the contradictions in the diagnosis value of the miR-451 in patients with CRC, deciphering the diagnostic/prognostic role of this miRNA in CRC will support the identification of a novel therapeutic target for CRC. Therefore, in the present meta-analysis, we evaluated the diagnostic value of miR-451 in CRC patients. The electronic databases of Embase, PubMed, ISI Web of Science, and Scopus systematically searched for relevant studies. The odds ratio (OR) with a 95% confidence interval (CI) was calculated to evaluate the association between miR-451 family expression and diagnosis of colorectal cancer. The parameters including sensitivity, specificity, and area under the curve (AUC) were obtained. The quality of evidence was evaluated using the Newcastle-Ottava Scale (NOS). This study involved 510 patients (45% female and 55% male) with CRC. The pooled analysis of the studies showed a significant association between low expression levels of miR-451 in patients with CRC (OR = 7.59; 95% CI 2.39 - 24.07; p = 0.001). The overall sensitivity and specificity were 0.95 (0.61 - 1) and 0.83 (0.43 - 0.99), respectively. The pooled AUC was 0.97 (0.88 - 1; p < 0.006). Results showed if the pre-test probability is 50% for a patient, the post-test probability will be 85%. The indices demonstrated the high potency of miR-451 as a diagnostic biomarker in patients with CRC. No publication bias was observed using the Begg's (p=0.85) and Egger's tests (p=0.45). A strong relationship between the low expression levels of miR-451 and CRC progression was observed. This finding suggests the miR-451 family may be helpful as a potential biomarker for the earlier diagnosis of colorectal cancer.

The exploration of cell population data in clinical use: Beyond infectious diseases

AbstractCell population data (CPD) is regarded as the fingerprint of a blood cell at a given moment. CPD parameters harbor information associated with cell morphology and can be automatically generated using modern hematological analyzers. Various studies have revealed many unique clinical applications for CPD, especially for infectious diseases, such as sepsis. For example, one monocyte‐related CPD parameter is the monocyte distribution width (MDW), which can be generated using a Beckman Coulter hematological analyzer. MDW has received FDA and CE approval for aiding in sepsis diagnosis in adult patients in the emergency department. Additionally, MDW can serve as a diagnostic biomarker in patients infected with SARS‐CoV‐2. CPD has also been widely explored for possible clinical applications beyond infectious diseases, such as for predicting myelodysplastic syndromes, screening for hematological malignancies, and detecting sterile inflammation. CPD parameter measurements are easily obtained and quite cost‐effective, making them practical for clinical use. However, there are some potential drawbacks of CPD parameters. Some pre‐analytical conditions can affect CPD values. Furthermore, CPD are specific to certain hematological analyzers and the result cannot be transferred between different analyzers. The practical usefulness of CPD reference intervals is also still questionable. In this review, wesummarize the current studies related to CPD and its clinical applications. Additional well‐designed clinical studies related to CPD are still expected.

A comprehensive evaluation of serum circCSPP1 as a novel diagnostic and prognostic biomarker for gastric cancer

PurposeGastric cancer (GC) has high incidence and mortality due to its low early screening efficiency. Circular RNAs (CircRNAs) are a new class of non-coding RNAs which is closely related to GC. Nevertheless, the clinical application value of circRNAs in GC are largely unknown. Therefore, we studied the role of a novel circRNA named circCSPP1 in patients with GC. MethodsCircRNA sequencing was performed to screen out the target molecule. Real-time fluorescent quantitative PCR (RT-qPCR) was utilized to detect the expression level of circCSPP1 in GC tissues, cells, and serum. Gel and Sanger sequencing were utilized to verify the ring structure of circCSPP1. RNase R enzyme digestion experiment and actinomycin D experiment were verifed the advantage of circCSPP1 as a diagnostic biomarker in patients with GC when that compared with linear RNA. The correlation between the expression level of serum circCSPP1 and clinicopathological data of GC patients was further analyzed. Receiver operating characteristic curve (ROC) and the area under ROC curve (AUC) were utilied to evaluate the diagnostic performance. ResultsCircCSPP1 has a circular structure which with resistance to RNA exonuclease digestion and long half-life compared with linear RNA. In our study, circCSPP1 was first found up-regulated in patients with GC. Serum circCSPP1 level was decreased significantly after surgical resection whereas increased after recurrence. High expression of circCSPP1 was associated with poor survival rates. The expression level of circCSPP1 was significantly correlated to tumor size, T stage, lymph node metastasis, and TNM stage. The AUC of serum circCSPP1 was 0.834, with high sensitivity and specificity in discriminating patients with GC from healthy donors. More importantly, the combined diagnosis of circCSPP1, CEA, and CA19–9 achieved the superior AUC of 0.882, with the highest specificity. ConclusionSerum circCSPP1 may prove to be a potential non-invasive auxiliary diagnostic biomarker for patients with GC.

Identification of biomarkers for abdominal aortic aneurysm in Behçet's disease via mendelian randomization and integrated bioinformatics analyses.

Behçet's disease (BD) is a complex autoimmune disorder impacting several organ systems. Although the involvement of abdominal aortic aneurysm (AAA) in BD is rare, it can be associated with severe consequences. In the present study, we identified diagnostic biomarkers in patients with BD having AAA. Mendelian randomization (MR) analysis was initially used to explore the potential causal association between BD and AAA. The Limma package, WGCNA, PPI and machine learning algorithms were employed to identify potential diagnostic genes. A receiver operating characteristic curve (ROC) for the nomogram was constructed to ascertain the diagnostic value of AAA in patients with BD. Finally, immune cell infiltration analyses and single-sample gene set enrichment analysis (ssGSEA) were conducted. The MR analysis indicated a suggestive association between BD and the risk of AAA (odds ratio [OR]: 1.0384, 95% confidence interval [CI]: 1.0081-1.0696, p = 0.0126). Three hub genes (CD247, CD2 and CCR7) were identified using the integrated bioinformatics analyses, which were subsequently utilised to construct a nomogram (area under the curve [AUC]: 0.982, 95% CI: 0.944-1.000). Finally, the immune cell infiltration assay revealed that dysregulation immune cells were positively correlated with the three hub genes. Our MR analyses revealed a higher susceptibility of patients with BD to AAA. We used a systematic approach to identify three potential hub genes (CD247, CD2 and CCR7) and developed a nomogram to assist in the diagnosis of AAA among patients with BD. In addition, immune cell infiltration analysis indicated the dysregulation in immune cell proportions.

Serum Metabolites as Diagnostic Biomarkers in Patients with Endometriosis.

Endometriosis diagnosis is usually delayed. The gold standard for diagnosing endometriosis is laparoscopy, which is invasive and accompanied by several risks. Currently, there are no effective non-invasive biomarkers for diagnosing endometriosis. Here, we investigated whether metabolites whose levels are altered in patients with endometriosis hold potential as diagnostic biomarkers for the disease. This case-control study involved 32 patients with endometriosis and 29 patients with other benign gynecological disease. The diagnosis of all patients was confirmed through postoperative histopathological examination, and the patients were divided into two groups: an endometriosis group (EM) and a control group. Fasting blood was collected and used for non-targeted metabolomic-based detection. The data were processed through principal component analysis, orthogonal partial least squares discriminant analysis, and significance analysis of microarrays. A univariate receiver operating characteristic curve was used to evaluate the diagnostic value of the metabolites. The metabolite profiles of patients with endometriosis were markedly different compared with those of the controls. In addition, several metabolic pathways, including biosynthesis of unsaturated fatty acids, arginine biosynthesis, and glutathione metabolism, were altered. Ornithine and medorinone showed better potential as biomarkers for endometriosis diagnosis than CA125. We analyzed the altered metabolic profiles in patients with endometriosis and found ornithine and medorinone as potential non-invasive biomarkers for endometriosis diagnosis, whereas the combined ornithine-medorinone diagnosis is more valuable. These findings may help advance research on non-invasive diagnostic biomarkers for endometriosis. Further research with an improved study design and a larger cohort should be performed to confirm the diagnostic potential and clinical application of these biomarkers.

Kaposi sarcoma herpesvirus viral load in bronchoalveolar lavage as a diagnostic marker for pulmonary Kaposi sarcoma.

Kaposi sarcoma is a vascular tumor that affects the pulmonary system. However, the diagnosis of airway lesions suggestive of pulmonary Kaposi sarcoma (pKS) is reliant on bronchoscopic visualization. We evaluated the role of Kaposi sarcoma herpesvirus (KSHV) viral load in bronchoalveolar lavage (BAL) as a diagnostic biomarker in patients with bronchoscopic evidence of pKS and evaluated inflammatory cytokine profiles in BAL and blood samples. In this retrospective study, we evaluated KSHV viral load and cytokine profiles within BAL and blood samples in patients who underwent bronchoscopy for suspected pKS between 2016 and 2021. KSHV viral load and cytokine profiles were obtained from both the circulation and BAL samples collected at the time of bronchoscopy to evaluate compartment-specific characteristics. BAL was centrifuged and stored as cell pellets and KSHV viral load was measured using primers for the KSHV K6 gene regions. We evaluated 38 BAL samples from 32 patients (30 with HIV co-infection) of whom 23 had pKS. In patients with airway lesions suggestive of pKS, there was higher KSHV viral load (median 3188 vs. 0 copies/10 6 cell equivalent; P = 0.0047). A BAL KSHV viral load cutoff of 526 copies/10 6 cells had a sensitivity of 72% and specificity of 89% in determining lesions consistent with pKS. Those with pKS also had higher IL-1β and IL-8 levels in BAL. The 3-year survival rate for pKS patients was 55%. KSHV viral load in BAL shows potential for aiding in pKS diagnosis. Patients with pKS also have evidence of cytokine dysregulation in BAL.

Hematological parameters as diagnostic biomarkers for patients with rosacea.

Rosacea is a chronic inflammatory skin disease. Systemic inflammation plays a vital role in the pathogenesis of rosacea. Many studies have reported hematological parameters as biomarkers for diseases with inflammatory processes. However, the diagnostic value of hematological parameters in rosacea remains a puzzle. This study involved 462 patients with rosacea, including erythematotelangiectatic rosacea (ETR, n = 179), papulopustular rosacea (PPR, n = 250), and phymatous rosacea (PhR, n = 33), and 924 healthy control subjects. Demographic, clinical, and laboratory information was collected and compared between rosacea subtypes. The hematological parameters of the patients and the healthy controls were compared retrospectively. The platelet volume (MPV) and platelet crit (PCT) were significantly upregulated, and the lower red cell distribution width (RDW) was significantly downregulated in rosacea compared to healthy controls, and they were identified as the diagnostic biomarkers for rosacea with area under the curve values of 0.828, 0.742, and 0.787, respectively. Comparing the hematological parameters among the three rosacea subtypes, we found that platelet-to-lymphocyte ratio and platelet-to-neutrophil ratio values in the ETR group were significantly higher than those in the PPR and PhR groups. The correlation between hematological parameters and clinical scores showed that RDW was negatively correlated with the Clinician Erythema Assessment score. However, there was no significant correlation between the Investigator Global Assessment score and hematological parameters. In conclusion, PCT, MPV, and RDW have diagnostic value for rosacea, and RDW is correlated with the severity of rosacea erythema, implying the potential applications of PCT, MPV, and RDW in the diagnosis and monitoring of rosacea.

Cerebrospinal fluid level of proNGF as potential diagnostic biomarker in patients with frontotemporal dementia

IntroductionFrontotemporal dementia (FTD) is an extremely heterogeneous and complex neurodegenerative disease, exhibiting different phenotypes, genetic backgrounds, and pathological states. Due to these characteristics, and to the fact that clinical symptoms overlap with those of other neurodegenerative diseases or psychiatric disorders, the diagnosis based only on the clinical evaluation is very difficult. The currently used biomarkers help in the clinical diagnosis, but are insufficient and do not cover all the clinical needs.MethodsBy the means of a new immunoassay, we have measured and analyzed the proNGF levels in 43 cerebrospinal fluids (CSF) from FTD patients, and compared the results to those obtained in CSF from 84 Alzheimer’s disease (AD), 15 subjective memory complaints (SMC) and 13 control subjects.ResultsA statistically significant difference between proNGF levels in FTD compared to AD, SMC and controls subjects was found. The statistical models reveal that proNGF determination increases the accuracy of FTD diagnosis, if added to the clinically validated CSF biomarkers.DiscussionThese results suggest that proNGF could be included in a panel of biomarkers to improve the FTD diagnosis.

Circulating miRNA-106b-5p As a Potential Biomarker for Coronary Artery Disease.

Coronary artery diseases (CAD) represent a significant global health concern and are recognized as a primary contributor to mortality on a worldwide scale. Early diagnosis of CAD is one of promising goal to manage this disorder. Recent investigations have highlighted the pivotal involvement of microRNAs (miRNAs) in diverse health conditions, notably CAD. The principal objective of this investigation was to identify appropriate miRNAs that could be employed for the early detection of CAD. In the present study, we analyzed dataset of CAD (GSE113079) and 100 differentially expressed mRNAs (DEmRNAs) were detected. The miRNAs that have a significant interaction with DEmRNAs were chosen. By computational prediction method, 5 miRNAs (miR-106b-5p, miR-20a-3p, miR-17-3p, miR-146a-5p, and miR-155-3p) were selected. Finally, we assessed the anticipated expression levels of microRNAs in CAD patients and healthy control groups. Our findings revealed a statistically significant elevation solely in the expression level of miR-106b-5p within the CAD group when compared to the control group (p>0.001). Our study demonstrated an elevation in the expression of miR-106b-5p in individuals diagnosed with CAD. This microRNA may be used as a diagnostic biomarker in patients with CAD. However, further investigations are needed to confirm these results.

Serum MRGPRX2 as a Long-term Biomarker for Iodinated Contrast Media-Induced Anaphylaxis.

The diagnosis of anaphylaxis is based on the clinical history. The utility of tryptase measurements in clinical setting is limited. Mas-related G protein-coupled receptor-X2 (MRGPRX2) is expressed in mast cells and is involved in the degranulation of these cells. We evaluated the potential of MRGPRX2 as a diagnostic biomarker in patients with iodinated contrast media (ICM)-induced immediate hypersensitivity reactions (IHRs). A total of 173 patients with documented ICM-induced IHR within 4 months from registration were enrolled and skin tests for the culprit ICM were performed. The time interval was evaluated as the duration between the onset of ICM-induced IHR and the measurement of serum MRGPRX2 levels. Serum MRGPRX2 concentration was determined using an enzyme-linked immunosorbent assay kit. Of the 173 patients, 33 and 140 were included in the anaphylaxis and non-anaphylaxis groups, respectively. Serum MRGPRX2 levels were significantly higher in the anaphylaxis than in the non-anaphylaxis group (29.9 ± 24.1 vs. 20.7±17.5, P = 0.044). Serum MRGPRX2 showed a moderate predictive ability for anaphylaxis, with an area under the curve of 0.61 (P = 0.058). When groups were classified based on the time interval, T1(0-2months) and T2 (2-4months), patients with anaphylaxis had higher MRGPRX2 levels compared to the non-anaphylaxis group in the T2 group (36.5±19.2 vs. 20.5±19.0, P = 0.035). This pilot study shows that serum MRGPRX2 is a potential long-term biomarker for predicting anaphylaxis, particularly ICM-induced anaphylaxis. Further studies are needed to determine the role of MRGPRX2 in anaphylaxis in a larger population of patients with various drug-induced IHRs.

Identification and validation of a seven cuproptosis-associated lncRNA signature to predict the prognosis of endometrial cancer.

Endometrial cancer (EC) is one of the most prevalent cancers in women. Long non-coding RNAs (lncRNAs) are potential diagnostic biomarkers in patients with EC. We obtained clinical information and transcriptome data for 552 patients with EC from The Cancer Genome Atlas database. Cuproptosis-associated lncRNAs were obtained through Pearson's correlation analysis. Univariate and multivariate Cox regression analyses were applied and a signature predicting overall survival (OS) among patients with EC was constructed. We also analyzed the tumor immune microenvironment and drug sensitivity. The results were validated by quantitative real time-polymerase chain reaction, and 5-ethynyl-2'-deoxyuridine and wound-healing assays. Seven cuproptosis-associated lncRNAs related to prognosis were screened out and a signature was constructed. OS was significantly superior in the low-risk group. In addition, patients in the low-risk group had more CD8+ T cell infiltration, a stronger type II interferon response, and greater cisplatin sensitivity. Expression levels of some of the lncRNAs were significantly increased by cuproptosis. Furthermore, silencing of lncRNA AC084117.1 significantly inhibited the proliferation and migration of EC cells. We constructed a seven cuproptosis-associated lncRNA signature to predict the prognosis of patients with EC with good predictive power.

Prognostic utility of MicroRNA-221 and interleukin-6 in cerebral ischemic stroke

Cerebral ischemic stroke has a significant mortality rate and persistent impairment. The initial diagnosis of stroke occurs by magnetic resonance imaging and computed tomography. There is a strong need for more accessible, less expensive, and non-invasive methods besides the neuroimaging methods. MicroRNAs (miRNAs) are critical regulators for ischemic stroke as they are involved in stroke pathophysiology. The goal of the current study was to determine whether microRNA-221 (miR-221) could be used as a diagnostic biomarker for patients with ischemic stroke, and whether it can serve as a promising indicator of the disease severity especially if combined with interleukin-6 (IL-6). The study included 90 subjects, 45 cerebral ischemic stroke patients and 45 controls. MiR-221 was evaluated by quantitative real-time polymerase chain reaction (q-PCR) and IL-6 by enzyme-linked immunosorbent assay (ELISA). Our study results revealed that the serum miR-221 level was significantly reduced in cerebral ischemic stroke patients when compared to the control group (p&lt;0.0001). In addition, serum miR-221 showed a significant negative correlation with cerebral stroke severity (p&lt;0.0001), whereas serum IL-6 showed a significant positive correlation with cerebral stroke severity (p &lt; 0.0001). We also analyzed the receiver operator characteristic (ROC) curve and found that area under the ROC curve (AUC) for severity of ischemic stroke by miR-221 was 0.97 (95% confidence intervall0.93–1, p&lt;0.001). Notably, the combination of serum miR-221 with IL-6 for prediction of ischemic stroke severity showed both increased sensitivity/specificity (AUC=0.99, 95% confidence interval 0.96-1, p&lt;0.001) than miR-221 alone. We concluded that miR-221 constituted a non-invasive, sensitive, and specific biomarker that could be used for diagnosis of ischemic stroke and for prediction of its severity.

Role of serum CAP1 protein in the diagnosis of patients with first-time acute myocardial infarction.

The dysregulation of adenylate cyclase-associated protein 1 (CAP1) is associated with a variety of inflammatory conditions. Here, we aimed to assess the role of serum CAP1 protein in predicting acute myocardial infarction (AMI), and to explore its effect and mechanism in vascular endothelial cells injury. ELISA was utilized to detected CAP1 protein expression in serum from 70 patients with first-time AMI at 0, 6, 12, 24, 48 hours and 7 days of the onset of chest pain. Receiver operating characteristic (ROC) curve analysis was administered to analyze the diagnostic power of CAP1 for AMI. The CCK-8 and 5-BrdU assays were applied to measure cell proliferation and inflammation in a model of oxidized low-density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVEC). Luciferase reporter gene assay and Western blotting were used to assess the activity of NF-κB pathway. Results showed that serum CAP1 protein expression was upregulated in patients with first-time AMI, its expression was highest at 12 hours of the onset of chest pain. CAP1 protein was positively associated with the levels of cTnI and ox-LDL. CAP1 showed a relatively high diagnostic accuracy in patients with first-time AMI compared with cTnI, and CAP1 combined with cTnI had superior diagnostic value than CAP1 and cTnI alone. The expression of CAP1 protein was increased in supernatants of ox-LDL induced HUVEC in a dose- and time-dependent manner. CAP1 inhibited cell proliferation but promoted inflammation, and induced the activation of NF-κB pathway in vitro. To sum up, increased serum CAP1 expression might serve as a novel diagnostic biomarker for patients with first-time AMI, the mechanism might be related to its induction of NF-κB pathway activation causing abnormal proliferation and inflammation and thus mediating vascular endothelial cell injury.

Lnc-HULC, miR-122, and sirtulin-1 as potential diagnostic biomarkers for psoriasis and their association with the development of metabolic syndrome during the disease course.

Psoriasis is a persistent inflammatory skin disorder driven by T cells. The disease is characterized by aberrant keratinocytes (KCs) differentiation, epidermal proliferation, and excessive hyperplasia of veins and arteries. The purpose of the study was to identify the levels of circulating lnc-HULC, miR-122, and Sirtuin 1 (SIRT-1) in psoriatic patients, evaluate their possible roles as diagnostic biomarkers, and link their levels with the development of metabolic syndrome during psoriasis progression. This study included 176 participants. The subjects were divided into four groups, with 44 participants in each group. All patients have undergone a complete history taking and clinical examination. Laboratory investigations included Low-density lipoprotein (LDL), High-density lipoprotein (HDL), Triglycerides (TG), Fasting blood sugar (FBS), and cholesterol plasma levels. Serum levels of miR-122 and lnc-HULC were examined by qRT-PCR. Serum levels of SIRT-1 were examined by ELISA. The serum concentrations of lnc-HULC and miR-122 were significantly higher in psoriatic participants compared to controls. Psoriatic patients' serum concentrations of SIRT-1 were much lower than those of healthy individuals. There was a negative association between SIRT-1 concentration and BMI, disease duration, PASI score, LDL, and cholesterol levels. The blood levels of lnc-HULC, miR-122, and SIRT-1 in psoriasis patients provide a promising role as diagnostic biomarkers in patients with and without metabolic syndrome.