Potential Diagnostic Marker Research Articles

Identification of Chronic Pancreatitis Associated microRNAs and Genes for the Diagnosis of Pancreatic Cancer.

The timely identification of both malignant and nonmalignant pancreatic lesions has the potential to significantly enhance prognosis and implement risk management strategies across various levels. microRNAs (miRs) and their corresponding targets play a crucial role in the development of pancreatic lesions and can serve as valuable diagnostic and therapeutic targets. The objective of our study was to investigate potential diagnostic markers that can effectively differentiate between malignant and nonmalignant pancreatic lesions. Gene Expression Omnibus (GEO) database with GSE24279 dataset was utilized to screen differentially expressed miRNAs (DEMs). We utilized the TargetScanHuman database to predict the target genes associated with hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p. Furthermore, a cohort comprising healthy individuals (n = 52), chronic pancreatitis (CP; n = 34), and pancreatic adenocarcinoma (PAAD; n = 53) patients was recruited to ascertain the levels of plasma markers. We identified 3 miRNAs (hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p) and 2 proteins (PCDH1 and AMN) as potential diagnostic markers for distinguishing between CP and PAAD. The area under the curve (AUC) values for all markers exceeded .800. Notably, a combination of plasma PCDH1 and AMN demonstrated excellent diagnostic performance (AUC = .921; 95% CI: .866-.977; sensitivity = .792; specificity = .941) in discriminating between CP and PAAD. In addition, the model of hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p yielded an AUC of .928, sensitivity of .830, and specificity of .912, respectively. Plasma levels of miRNAs (hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p) and their corresponding targets (PCDH1 and AMN) hold promise as potential biomarkers for predicting PAAD in patients with CP.

Computed tomography-based radiological gynecomastia in SBMA as an independent differential diagnostic biomarker: a retrospective study.

Spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS) are motor neuron disorders that demonstrate overlapping clinical features, especially in the early stage. Therefore, the aim of this study was to investigate the utility of chest tomography (CT) imaging in distinguishing between SBMA and ALS. This was a retrospective study reviewing CT images from patients with SBMA and sporadic ALS and those in the control group. The CT images were assessed to measure the diameter and morphology of glandular tissue associated with gynecomastia. We compared CT-measured gynecomastia between the SBMA, ALS, and control groups. Additionally, correlation analyses were performed between the quantitative measurements of gynecomastia obtained from CT scans and various clinical/laboratory parameter in the SBMA group. 15 chest CT images were collected from SBMA, 41 from ALS, and 29 from control group. No statistical differences were observed in BMI, functional scales, or age at the time of CT scans between the SBMA and ALS groups. Despite similar functional scales and age in both groups, the mean glandular tissue diameter of breast tissue observed in chest CT imaging differed significantly between SBMA, ALS, and controls: 32.22 ± 12.57mm, 15.91 ± 4.81mm, and 15.76 ± 7.26mm, respectively. This disparity allowed for the differentiation of SBMA from ALS and controls with statistical significance. Clinical gynecomastia was 80%, while radiological gynecomastia was 93.3% in SBMA. A significantly higher prevalence of diffuse glandular morphology pattern in SBMA (50%) was observed, contrasting with the predominance of nodular morphology in ALS and controls (9.1% and 20%). Correlative analysis between glandular tissue diameter and other clinical/laboratory parameters within the SBMA group showed no specific finding. CT-based radiological gynecomastia effectively differentiated SBMA from ALS. These findings support the usefulness of radiological gynecomastia as a potential differential diagnostic marker for SBMA, especially in the early stages.

Immunohistochemical Localization of Fibroblast Activation Protein in Coronary Arteries with Different Forms of Atherosclerosis

Background: Fibroblast activation protein (FAP) is a cell surface glycoprotein expressed by myofibroblasts in areas of active tissue remodeling. It plays a potentially important role in cardiac remodeling, atherosclerotic plaque formation, and plaque rupture. Given the distinct pathophysiology and morphology of different forms of atherosclerosis, we analyzed FAP expression in human coronary vessels with no coronary artery disease, atherosclerotic plaques at different levels of progression, and other distinct forms of coronary disease in post bypass vein grafting and cardiac allograft vasculopathy after a heart transplant. Methods: Immunohistochemical staining with monoclonal F19 mouse anti-human FAP antibody was performed to identify FAP in human atherosclerotic plaques, coronary bypass atherosclerosis, and post-transplant arteriosclerosis. The presence and distribution of FAP in different types and stages of human atherosclerosis were compared. Results: There was no FAP staining in patients with no significant coronary disease. All different types of human atherosclerotic lesioning lesions showed the presence of FAP expression, with different staining patterns in advanced atherosclerotic plaque, vein graft atherosclerosis lesions, and arteriosclerosis after a heart transplant. Conclusions: These data suggest that FAP may be a potential diagnostic marker and target for interventions, not only in coronary atherosclerotic plaque, but also in other forms of coronary disease, which have distinct pathophysiologies and currently limited treatment options.

Gene expression profiling in B-cell non-Hodgkin lymphomas

Abstract BACKGROUND: Gene expression profiling has become a fundamental tool in cancer diagnosis and management. B-cell non-Hodgkin lymphoma (B-NHL) is a group of malignant neoplasms originating from the lymphoid tissues, mainly the lymph nodes and the gene expression technique was used to unravel its complexity and aid in clinical decision-making. OBJECTIVES: The aims of this study were to find the significance of gene expression profiling focusing on colony-stimulating factor 1 receptor (CSF1R), myeloid differentiation factor 88 (MyD88), and tumor necrosis factor-α (TNF-α) as a promising approach in B-NHL diagnosis and their comparison with healthy controls. PATIENTS, MATERIALS AND METHODS: The current clinical prospective study was mediated from June 1, 2021, to December 30, 2022, of NHL patients in Kurdistan, Iraq. Seventy-three patients were recruited from Nanakali Hospital for Blood Diseases and Cancer, Erbil. The integration of gene expression biomarkers uses quantitative real-time polymerase chain reaction technique to diagnose B-NHL. Specifically, we focused on three key genes MyD88, TNF, and CSF1R whose expression profiles were analyzed in B-NHL patients and controls. We leveraged a dataset to explore gene expression patterns in B-NHL and applied classification algorithms to distinguish between B-NHL patients and controls. RESULTS: The initial results show the overall lower CSF1R expression in B-NHL as compared to the controls and a significant reduction in CSF1R expression in females (≤50 years and >50 years). The result considers lower CSF1R expression in B-NHL males (≤50 years) and higher but not significant in males (>50 years). CONCLUSIONS: These B-NHL-expressed genes may be considered potential diagnostic markers with their meaningful comparisons to control groups, and they could be proposed to guide the management of patients and facilitate their stratification into clinical trials.

The gut-eye axis: from brain neurodegenerative diseases to age-related macular degeneration.

Age-related macular degeneration Is a serious neurodegenerativo disease of the retina that significantly impacts vision. Unfortunately, the specific pathogenesis remains unclear, and effective early treatment options are consequently lacking. The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host. The intestinal microbiome undergoes dynamic changes owing to age, diet, genetics, and other factors. Such dysregulation of the intestinal flora can disrupt the microecological balance, resulting in immunological and metabolic dysfunction in the host, and affecting the development of many diseases. In recent decades, significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract, including the brain. Indeed, several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Similarly, the role of the "gut-eye axis" has been confirmed to play a role in the pathogenesis of many ocular disorders. Moreover, age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies. As such, the intestinal flora may play an important role in age-related macular degeneration. Given the above context, the present review aims to clarify the gut-brain and gut-eye connections, assess the effect of intestinal flora and metabolites on age-related macular degeneration, and identify potential diagnostic markers and therapeutic strategies. Currently, direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited, while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration. Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions, while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.

Identification and validation of core genes associated with polycystic ovary syndrome and metabolic syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting women of reproductive age, affecting reproductive health, and increasing the incidence of diabetes mellitus and hypertension. Metabolic syndrome (MetS) is the most common metabolic disorder. Although clinical studies have shown a close association between PCOS and MetS, the molecular mechanisms are unknown. In this study, datasets of PCOS and MetS were obtained from the Gene Expression Omnibus database; differential expression analysis and weighted gene coexpression network analysis (WGCNA) were performed; and gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses also performed of differentially expressed genes (DEGs). The PCOS- and MetS-coexpressed DEGs were subsequently intersected with the coexpressed genes in the WGCNA module to obtain the core genes. By constructing receiver operating characteristic curves, we verified the predictive effects of the core genes. We also validated the expression of the core genes in the datasets. Finally, we verified the expression of the core genes by quantitative polymerase chain reaction in human follicular fluid granulosa cells. In addition, we used Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts to analyze the immune infiltration of immune cells in PCOS and MetS. Finally, we obtained 52 coexpressed DEGs of PCOS and MetS and 3 coexpressed genes in the WGCNA module. By taking the intersection of coexpressed DEGs and coexpressed genes of the WGCNA module, we get ELOVL fatty acid elongase 7 (ELOVL7) as the core gene. Receiver operating characteristic curve analysis showed that ELOVL7 is a reliable biological marker for PCOS and MetS. The expression level of ELOVL7 in human follicular fluid granulosa cells from PCOS patients was significantly higher than that of controls, as verified by quantitative polymerase chain reaction. This study provides the first evidence of the role of ELOVL7 in developing PCOS and MetS. This gene may serve as a potential diagnostic marker and therapeutic target for both conditions.

Unlocking the Potential of Circulating miRNAs as Biomarkers in Glioblastoma

Using microRNAs (miRNAs) as potential circulating biomarkers in diagnosing and treating glioblastoma (GBM) has garnered a lot of scientific and clinical impetus in the past decade. As an aggressive primary brain tumor, GBM poses challenges in early detection and effective treatment with significant current diagnostic constraints and limited therapeutic strategies. MiRNA dysregulation is present in GBM. The intricate involvement of miRNAs in altering cell proliferation, invasion, and immune escape makes them prospective candidates for identifying and monitoring GBM diagnosis and response to treatment. These miRNAs could play a dual role, acting as both potential diagnostic markers and targets for therapy. By modulating the activity of various oncogenic and tumor-suppressive proteins, miRNAs create opportunities for precision medicine and targeted therapies in GBM. This review centers on the critical role and function of circulating miRNA biomarkers in GBM diagnosis and treatment. It highlights their significance in providing insights into disease progression, aiding in early diagnosis, and potential use as targets for novel therapeutic interventions. Ultimately, the study of miRNA would contribute to improving patient outcomes in the challenging landscape of GBM management.

Potential cardiac-derived exosomal miRNAs involved in cardiac healing and remodeling after myocardial ischemia–reperfusion injury

Migratory cells exist in the heart, such as immune cells, fibroblasts, endothelial cells, etc. During myocardium injury, such as ischemia–reperfusion (MIRI), cells migrate to the site of injury to perform repair functions. However, excessive aggregation of these cells may exacerbate damage to the structure and function of the heart, such as acute myocarditis and myocardial fibrosis. Myocardial injury releases exosomes, which are a type of vesicle with signal transduction function and the miRNA carried by exosomes can control cell migration function. Therefore, regulating this migratory cell population through cardiac-derived exosomal miRNA is crucial for protecting and maintaining cardiac function. Through whole transcriptome RNA sequencing, exosomal miRNA sequencing and single-cell dataset analysis, we (1) determined the potential molecular regulatory role of the lncRNA‒miRNA‒mRNA axis in MIRI, (2) screened four important exosomal miRNAs that could be released by cardiac tissue, and (3) screened seven genes related to cell locomotion that are regulated by four miRNAs, among which Tradd and Ephb6 may be specific for promoting migration of different cells of myocardial tissue in myocardial infarct. We generated a core miRNA‒mRNA network based on the functions of the target genes, which may be not only a target for cardiac repair but also a potential diagnostic marker for interactions between the heart and other tissues or organs. In conclusion, we elucidated the potential mechanism of MIRI in cardiac remodeling from the perspective of cell migration, and inhibition of cellular overmigration based on this network may provide new therapeutic targets for MIRI and to prevent MIRI from developing into other diseases.

Dysregulation of pseudouridylation in small RNAs contributes to papillary thyroid carcinoma metastasis

BackgroundPrevious studies have indicated that ψ-modified small RNAs play crucial roles in tumor metastasis. However, the ψ-modified small RNAs during metastasis of PTC are still unclear.MethodsWe compared the pseudouridine synthase 7 (PUS7) alteration between metastatic and non-metastatic PTCs, and investigated its correlation with clinicopathological features. Additionally, we employed a small RNA ψ modification microarray to examine the small RNA ψ modification profile in both metastatic and non-metastatic PTCs, as well as paired paracancerous tissues. The key molecule involved in ψ modification, pre-miR-8082, was identified and found to regulate the expression of CD47. Experiments in vitro were conducted to further investigate the function of PUS7 and CD47 in PTC.ResultsOur results demonstrated that PUS7 was down-regulated in PTC and was closely associated with metastasis. Moreover, the ψ modification of pre-miR-8082 was found to be decreased, resulting in down-expression of pre-miR-8082 and miR-8082, leading to the loss of the inhibitory effect on CD47, thereby promoting tumor migration.ConclusionsOur study demonstrates that PUS7 promotes the inhibition of CD47 and inhibits metastasis of PTC cells by regulating the ψ modification of pre-miR-8082. These results suggest that PUS7 and ψ pre-miR-8082 may serve as potential targets and diagnostic markers for PTC metastasis.

Identification of novel biomarkers for atherosclerosis using single-cell RNA sequencing and machine learning.

Atherosclerosis (AS) is a predominant etiological factor in numerous cardiovascular diseases, with its associated complications such as myocardial infarction and stroke serving as major contributors to worldwide mortality rates. Here, we devised dependable AS-related biomarkers through the utilization of single-cell RNA sequencing, weighted co-expression network (WGCNA), and differential expression analysis. Furthermore, we employed various machine learning techniques (LASSO and SVM-RFE) to enhance the identification of AS biomarkers, subsequently validating them using the GEO dataset. Following this, CIBERSORT was employed to investigate the correlation between biomarkers and infiltrating immune cells. Consequently, 256 differentially expressed genes (DEGs) were selected in samples of AS and normal. GO and KEGG analyses indicated that these DEGs may be related to the negative regulation of leukocyte-mediated immunity, leukocyte cell-cell adhesion, and immune system processes. Notably, C1QC and COL1A1 were pinpointed as potential diagnostic markers for AS, a finding that was further validated in the GSE21545 dataset. Moreover, the area under the curve (AUC) values for these markers exceeded 0.8, underscoring their diagnostic utility. Analysis of immune cell infiltration revealed that the expression of C1QC was correlated with M0 macrophages, gamma delta T cells, activated mast cells and memory B cells. Similarly, COL1A1 expression was linked to M0 macrophages, memory B cells, activated mast cells, gamma delta T cells, and CD4 native T cells. Finally, these results were validated using mice and human samples through immunofluorescence, immunohistochemistry, and ELISA analysis. Overall, C1QC and COL1A1 would be potential biomarkers for AS diagnosis, and that would provides novel perspectives on the diagnosis and treatment of AS.

Exploring Lysophosphatidylcholine as a Biomarker in Ischemic Stroke: The Plasma-Brain Disjunction.

Lipids and their bioactive metabolites, notably lysophosphatidylcholine (LPC), are increasingly important in ischemic stroke research. Reduced plasma LPC levels have been linked to stroke occurrence and poor outcomes, positioning LPC as a potential prognostic or diagnostic marker. Nonetheless, the connection between plasma LPC levels and stroke severity remains unclear. This study aimed to elucidate this relationship by examining plasma LPC levels in conjunction with brain LPC levels to provide a deeper understanding of the underlying mechanisms. Adult male Sprague-Dawley rats underwent transient middle cerebral artery occlusion and were randomly assigned to different groups (sham-operated, vehicle, LPC supplementation, or LPC inhibition). We measured multiple LPC species in the plasma and brain, alongside assessing sensorimotor dysfunction, cerebral perfusion, lesion volume, and markers of BBB damage, inflammation, apoptosis, and oxidative stress. Among five LPC species, plasma LPC(16:0) and LPC(18:1) showed strong correlations with sensorimotor dysfunction, lesion severity, and mechanistic biomarkers in the rat stroke model. Despite notable discrepancies between plasma and brain LPC levels, both were strongly linked to functional outcomes and mechanistic biomarkers, suggesting that LPC's prognostic value is retained extracranially. This study advances the understanding of LPC as a blood marker in ischemic stroke and highlights directions for future research to further elucidate its association with stroke severity, particularly through investigations in more clinically representative models.

KNTC1 functions as a potential biomarker and oncogene regulating proliferation, migration and apoptosis in gastric cancer

BackgroundAs one of the most prevalent cancers, gastric cancer (GC) exhibits a remarkably high morbidity and mortality rate. To date, effective diagnostic and prognostic markers and therapeutic targets for GC are still lacking. Kinetochore associated 1 (KNTC1) is one of the proteins involved in chromosome segregation. However, the diagnostic and prognostic value of KNTC1 and its biological function in GC remain unknown. MethodsIn this study, Gene Expression Omnibus (GEO) datasets were utilized to identify differentially expressed genes (DEGs). Prognostic and diagnostic value were assessed by Kaplan-Meier plotter and receiver operating characteristic (ROC) curve. The expression of KNTC1 was verified by q-PCR, immunohistochemistry (IHC) and Western blotting. Subsequently, KNTC1 knockdown was employed to investigate its effect on GC cells. Gene set enrichment analysis (GSEA) revealed a pathway regulated by KNTC1, which was further verified by Western blotting. ResultsFour highly expressed genes (ESPL1, RAD54L, KNTC1, TACC3) were identified as biomarkers for GC diagnosis and prognosis. Notably, the value of KNTC1 as a biomarker for GC was newly revealed. Single-cell and immune analyses revealed that KNTC1 contributed to the suppression of the GC immune microenvironment. In clinical samples, we demonstrated high expression of KNTC1 in GC tissues. KNTC1 knockdown suppressed proliferation and migration while promoting apoptosis of GC cells. Additionally, KNTC1 may affect GC cells by regulating the PI3K/Akt/mTOR pathway. ConclusionsKNTC1 acts as a potential diagnostic and prognostic marker for GC. It may promote proliferation and migration while inhibiting apoptosis of GC cells via the PI3K/Akt/mTOR pathway.

Platelet-to-Lymphocyte Ratio as a Potential Diagnostic Marker for Acute Coronary Syndromes in Resource-Limited Settings: A Cross-Sectional Study from Single Center in Banten, Indonesia

Background: Acute coronary syndrome (ACS) poses a significant global health burden, particularly in resource-limited settings where access to advanced diagnostic tools is often constrained. The platelet-to-lymphocyte ratio (PLR), a simple and readily available marker from routine blood tests, has shown promise as a potential diagnostic tool for ACS. This study aimed to evaluate the diagnostic accuracy of PLR in identifying ACS patients in a resource-limited setting in Indonesia. Methods: A cross-sectional study was conducted at Hermina Periuk Hospital, Tangerang, Banten, Indonesia, between December 2020 and December 2022. Patients presenting to the Emergency Room with a diagnosis of ACS were included. PLR was calculated from complete blood count data, and cardiac troponin I (cTnI) served as the gold standard for ACS diagnosis. The diagnostic performance of PLR in predicting elevated cTnI levels was assessed. Results: Of the 121 patients initially identified, 39 met the inclusion and exclusion criteria. Elevated PLR values (>116) were observed in 25 patients (64.1%), while 15 patients (38.5%) had elevated cTnI levels. A statistically significant correlation was found between elevated PLR and elevated cTnI (p = 0.018). No significant association was observed between neutrophil-to-lymphocyte ratio (NLR) and elevated cTnI. Conclusion: PLR demonstrates potential as a diagnostic marker for ACS in resource-limited settings. Its simplicity, accessibility, and cost-effectiveness make it a valuable tool for early identification and risk stratification of ACS patients, particularly in areas with limited access to advanced cardiac diagnostics.

Integrin subunit beta 6 is a potential diagnostic marker for acute kidney injury in patients with diabetic kidney disease: a single cell sequencing data analysis

Background Diabetic kidney disease (DKD), a prevalent complication of diabetes mellitus, is often associated with acute kidney injury (AKI). Thus, the development of preventive and therapeutic strategies is crucial for delaying the progression of AKI and DKD. Methods The GSE183276 dataset, comprising the data of 20 healthy controls and 12 patients with AKI, was downloaded from the Gene Expression Omnibus (GEO) database to analyze the AKI group. For analyzing the DKD group, the GSE131822 dataset, comprising the data of 3 healthy controls and 3 patients with DKD, was downloaded from the GEO database. The common differentially expressed genes (DEGs) in renal tubular epithelial cells (TECs) were subjected to enrichment analyses. Next, a protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes database to analyze gene-related regulatory networks. Finally, the AKI animal models and the DKD and AKI cell models were established, and the reliability of the identified genes was validated using quantitative real-time polymerase chain reaction analysis. Results Functional analysis was performed with 40 common DEGs in TECs. Eight hub genes were identified using the PPI and gene-related networks. Finally, validation experiments with the in vivo animal model and the in vitro cellular model revealed the four common DEGs. Four DEGs that share molecular mechanisms in the pathogenesis of DKD and AKI were identified. In particular, the expression of Integrin Subunit Beta 6(ITGB6), a hub and commonly upregulated gene, was upregulated in the in vitro models. Conclusion ITGB6 may serve as a biomarker for early AKI diagnosis in patients with DKD and as a target for early intervention therapies.

Functional neural substrates of Parkinson’s disease and potential underpinnings of acute responses to acupuncture stimulation

Parkinson’s disease is a heterogenous neurodegenerative disorder with a wide variety of motor and non-motor symptoms. This study used resting-state fMRI to identify the neural substrates of PD and explore the acute neural response to acupuncture stimulation in 74 participants (50 patients with PD and 24 healthy controls). All participants with PD were evaluated for the severity of symptoms using the Unified Parkinson’s Disease Rating Scale and Balance Master. The z-transformed fractional amplitude of low-frequency fluctuation analysis showed significant differences between the PD and healthy controls in the cerebellar regions, which are thought to play a crucial role in PD pathology. Subsequently, seed-based functional connectivity of the cerebellum with the frontal, parietal, and limbic regions was identified as a potential diagnostic marker for PD. In addition, spontaneous neural activity in the precentral gyrus and thalamus was significantly associated with the severity of PD symptoms. Neural activity in the precentral gyrus, precuneus, and superior temporal gyrus showed a significant correlation with Balance Master indicators. Finally, acupuncture stimulation at GB34 significantly reduced the activity of the occipital regions in patients with PD, but this effect was not observed in healthy controls. The mixed-effects analysis revealed an interaction effects between group and acupuncture stimulation, suggesting that the modulatory effects of acupuncture could differ depending on disease status. Therefore, this study suggests the neural substrates of PD and potential underpinnings of acute neural response to acupuncture stimulation.

MiRNA expression profiling reveals a potential role of microRNA-148b-3p in cerebral vasospasm in subarachnoid hemorrhage

Cerebral vasospasm (CVS) is an important contributor to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH), leading to high morbidity and long-term disability. While several microRNAs (miRNAs) have been implicated in vasospasm, the underlying mechanisms for CVS remain poorly understood. Our study aims to identify miRNAs that may contribute to the development of CVS. Whole-blood samples were obtained during or outside of vasospasm from aSAH patients whose maximal vasospasm was moderate or severe. MiRNAs were isolated from serial whole-blood samples, and miRNA sequencing was performed. Differentially expressed miRNAs were identified and the expression levels in patients’ samples were verified using real-time qPCR. The biological functions of identified miRNA were evaluated in human brain endothelial cells (HBECs). MiRNA profiling revealed significant upregulation of miR-148b-3p in patients during CVS. We demonstrated that miR-148b-3p directly targeted and decreased the expression of ROCK1, affecting cell proliferation, migration, and invasion of HBECs through the ROCK-LIMK-Cofilin pathway. We propose that the upregulation of miRNA-148b-3p plays a role in the development of CVS by regulating actin cytoskeletal dynamics in HBECs, which is crucial for vascular function. Our study highlights miR-148b-3p as a potential diagnostic marker as well as therapeutic target for CVS following aSAH.

Immunohistochemical Expression of P63 and P40 in Squamous Cell Carcinoma of Head and Neck

Background: Squamous cell carcinoma (SCC) in head and neck region has a high worldwide prevalence. Increased accuracy in diagnosis is achieved by immunohistochemical markers. Objectives: To evaluate the immunohistochemical expression of p63 and p40 in SCC and correlate with histological grades to determine p40 as a better potential diagnostic immunohistochemical marker for SCC. Methods: Descriptive cross-sectional study was conducted on eighty-three cases of SCC of head and neck from March 2020 to February,2022 at Pathology Department, KEMU, Lahore. Data including age, sex, risk factors and tumor site was collected. SCC grading was done on H&E stained tissue sections. Staining with p63 and p40 was performed and independently scored for percentage of tumor cells stained and intensity of nuclear staining. The results were compared using H-scores in all grades of SCC. Data was entered in Statistical Package for Social Sciences(SPSS-26). Quantitative variables like age were presented as mean ±SD. Qualitative variables as frequency and percentages. Correlation of two groups was done by applying Chi-square test. P value ≤0.05 was taken as significant. Results: SCC was graded according to the W.H.O. grading system. All cases stained positive for p63 and p40. Strong nuclear staining by p40 was observed in 65.02% cases versus 42.17% by p63. The mean tumor area stained by p40 was greater than p63 (90.35% vs 75.5%) in all cases. A significant higher mean H-score for p40 (9.69±2.86) versus p63 (7.05±3.12) was observed as indicated by significant P-value. The mean H-score of p40 immunoreactivity was 10.11 and p63 was 6.00 in poorly differentiated SCC. Males comprised 74.70% cases whereas females 25.30% only. SCC in oral cavity was (96.39%) followed by oropharynx and larynx. Conclusion: P40 immunohistochemical marker was better compared to P63 for the diagnosis of SCC particularly in poorly differentiated SCC.

Exosome-related gene identification and diagnostic model construction in hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (HIRI) may cause severe hepatic impairment, acute hepatic insufficiency, and multiorgan system collapse. Exosomes can alleviate HIRI. Therefore, this study explored the role of exosomal-related genes (ERGs) in HIRI using bioinformatics to determine the underlying molecular mechanisms and novel diagnostic markers for HIRI. We merged the GSE12720, GSE14951, and GSE15480 datasets obtained from the Gene Expression Omnibus (GEO) database into a combined gene dataset (CGD). CGD was used to identify differentially expressed genes (DEGs) based on a comparison of the HIRI and healthy control cohorts. The impact of these DEGs on HIRI was assessed through gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). ERGs were retrieved from the GeneCards database and prior studies, and overlapped with the identified DEGs to yield the set of exosome-related differentially expressed genes (ERDEGs). Functional annotations and enrichment pathways of these genes were determined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Diagnostic models for HIRI were developed using least absolute shrinkage and selection operator (LASSO) regression and support vector machine (SVM) algorithms. Key genes with diagnostic value were identified from the overlap, and single-sample gene-set enrichment analysis (ssGSEA) was conducted to evaluate the immune infiltration characteristics. A molecular regulatory interaction network was established using Cytoscape software to elucidate the intricate regulatory mechanisms of key genes in HIRI. Finally, exosome score (Es) was obtained using ssGSEA and the HIRI group was divided into the Es_High and Es_Low groups based on the median Es. Gene expression was analyzed to understand the impact of all genes in the CGD on HIRI. Finally, the relative expression levels of the five key genes in the hypoxia-reoxygenation (H/R) model were determined using quantitative real-time PCR (qRT-PCR). A total of 3810 DEGs were identified through differential expression analysis of the CGD, and 61 of these ERDEGs were screened. Based on GO and KEGG enrichment analyses, the ERDEGs were mainly enriched in wound healing, MAPK, protein kinase B signaling, and other pathways. GSEA and GSVA revealed that these genes were mainly enriched in the TP53, MAPK, TGF[Formula: see text], JAK-STAT, MAPK, and NFKB pathways. Five key genes (ANXA1, HNRNPA2B1, ICAM1, PTEN, and THBS1) with diagnostic value were screened using the LASSO regression and SVM algorithms and their molecular interaction network was established using Cytoscape software. Based on ssGSEA, substantial variations were found in the expression of 18 immune cell types among the groups (p < 0.05). Finally, the Es of each HIRI patient was calculated. ERDEGs in the Es_High and Es_Low groups were enriched in the IL18, TP53, MAPK, TGF[Formula: see text], and JAK-STAT pathways. The differential expression of these five key genes in the H/R model was verified using qRT-PCR. Herein, five key genes were identified as potential diagnostic markers. Moreover, the potential impact of these genes on pathways and the regulatory mechanisms of their interaction network in HIRI were revealed. Altogether, our findings may serve as a theoretical foundation for enhancing clinical diagnosis and elucidating underlying pathogeneses.

Bibliometric analysis of microRNAs and Parkinson's disease from 2014 to 2023.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons. Recent research has emphasized a significant correlation between microRNAs (miRNAs) and PD. To identify key research areas, provide a comprehensive overview of current research in various fields, and propose potential directions for future studies, a bibliometric analysis was conducted on the involvement of miRNAs in Parkinson's disease from 2014 to 2023. Relevant literature records were collected from the Web of Science Core Collection on February 29, 2024. Subsequently, the data underwent analysis using the Bibliometrix R package and VOSviewer (version 1.6.19). The annual scientific publications on miRNAs and Parkinson's disease demonstrated an increasing trend, with an annual growth rate of 12.67%. China, the United States, and India emerged as the top three most productive countries/regions. The University of Barcelona had the highest annual publications, followed by Central South University and the Helmholtz Association. The INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES held the top position in terms of H-index and total citations, reflecting its extensive influence and prolific publication output. Kim, J., Junn, E., Hébert, S.S., and Doxakis, E. were the most frequently co-cited authors in the field. Based on the analysis of keywords, the most frequently occurring terms included "alpha-synuclein," "neurodegenerative disease," "exosome," "neuroinflammation," "oxidative stress," "autophagy," and "amyotrophic lateral sclerosis," which have emerged as prominent research topics. Concurrently, there has been notable interest in topics such as "ceRNA," "lncRNAs," "mitochondrial dysfunction," and "circular RNA." This study focused on identifying emerging trends and critical research topics in the bibliometric analysis of microRNAs related to Parkinson's disease. These findings highlight the diverse research landscape and evolving trend of miRNA-related research in PD. The field of miRNA research in Parkinson's disease is actively exploring the underlying mechanisms of miRNA function, identifying potential diagnostic markers, and developing innovative therapeutic strategies. The results of our study offer significant contributions to researchers' ability to track contemporary developments and guide the trajectory of future research in this domain.

Systemic Juvenile Idiopathic Arthritis and arthralgia - can it be diagnosed early within the window period? – An observation of serum biomarkers and analysis with other differential conditions in children

Background: Systemic juvenile idiopathic arthritis (sJIA)is a cause of persisting arthralgia which is often missed. Diagnosing sJIA can be challenging, especially when overt arthritis is absent at presentation, highlighting the need for a diagnostic biomarker. Few recent studies have assessed potential biomarkers for sJIA, however, there is no consensus in detecting early. We conducted a study evaluating serum IL-1, IL-6, IL-18, S100A8, and S100A9 as potential diagnostic markers to distinguish sJIA from other conditions presenting as joint pain in children. Methods: A prospective study was conducted in our institute from May-2019 to October-2020 in children under 16 years, who had persisting arthralgia. Serum concentrations of IL-1, IL-6, IL-18, S100A9, and S100A8 were determined using ELISA kits. Receiver operating curve (ROC) analysis was used to determine the cut-off values for IL-1, IL-6, IL-18, S100A8, and S100A9 for differentiating sJIA from other causes of joint pain and fever. Results- Out of 47 children who presented with joint pain and fever 19 of them were eventually diagnosed with sJIA. In the other 28 children, arthralgia and fever was attributed to conditions other than sJIA (non-sJIA). The non-sJIA group comprised children with acute lymphoblastic leukemia, hemophagocytic histiocytosis, systemic lupus erythematosus, Kawasaki disease, Kikuchi disease, and inflammatory bowel disease. Serum levels of IL-18, S100A8, and S100A9 were significantly higher in patients with sJIA compared to the non-sJIA group (p&lt;0.05). The area under the curve (AUC) was significant for IL-18(77.9%), S100A8 (74.9%), and S100A9(71.2%). A serum IL-18 cut-off level of &gt; 2030.45 pg/ml was useful for differentiating between sJIA and other diseases with a sensitivity of 66.67% and specificity of 75.86% for the diagnosis of sJIA. Conclusion- Serum IL-18, S100A8, and S100A9 can be useful in differentiating sJIA early from other causes of persisting arthralgia in children provided with appropriate identification of symptomatology and suspicion.