Potential Biomarkers Research Articles

Combination of transcriptomics and proteomics for analyzing potential biomarker and molecular mechanism underlying skeletal muscle atrophy.

The skeletal muscle atrophy is prevalently occurred in numerous chronic disease complications. Despite its important clinical significance, there are currently no therapeutic drugs, so new biomarkers and molecular mechanisms need to be discovered urgently. Transcriptome and proteome sequencing data were collected from normal and skeletal muscle atrophic mice. The differentially expressed genes (DEGs) and proteins (DEPs) were analyzed. Applying PPI analysis to obtain overlapping genes and proteins, which were next subjected to GO and KEGG enrichment analysis. Combined analysis of transcriptomics and proteomics was performed to get key genes that were simultaneously found in GO and KEGG enrichment results. Subsequently, RT-qPCR and immunofluorescence were constructed to verify the expression of screened key genes. By combination of transcriptomics, proteomics analysis and RT-qPCR results, we identified 14 key genes (Cav1, Col3a1, Dnaja1, Postn, Ptges3, Cd44, Clec3b, Igfbp6, Lamc1, Alb, Itga6, Mmp2, Timp2 and Cd9) that were markedly different in atrophic mice. Single-gene GSEA and immunofluorescence suggested Cd9 was probably the biomarker for skeletal muscle atrophy. Our study hinted that Cd9 was potential biomarker and may interfere with skeletal muscle atrophy through process of aerobic respiration, oxidative phosphorylation, and metabolism of amino acids and fatty acids. The present study holds the subsequent significance: Frist, we investigated biomarkers for skeletal muscle atrophy using multi-omics approach. A total of 14 genes were markedly different in skeletal muscle atrophic mice. We finally found Cd9 is a potential biomarker for skeletal muscle atrophy. Our work presents novel biomarkers and potential regulatory mechanisms for the early detection and intervention of muscle atrophy.

ZNF695, A Potential Prognostic Biomarker, Correlates with Im mune Infiltrates in Cervical Squamous Cell Carcinoma and Endoce rvical Adenocarcinoma: Bioinformatic Analysis and Experimental Verification.

The role of Zinc Finger Protein 695 (ZNF695) is unclear in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). The objective of this study was to conduct a comprehensive analysis and experimental validation of ZNF695 in CESC. The study investigated the expression of ZNF695 in both pan-cancer and CESC, utilizing data from The Cancer Genome Atlas (TCGA) database to assess its diagnostic value. The present study investigated the association between ZNF695 expression levels and clinical characteristics, as well as prognosis, in patients with CESC. The study explored potential regulatory networks involving ZNF695, including its association with immune infiltration, immune score, stemness index based on mRNA expression (mRNAsi), and drug sensitivity in CESC. We explored the expression of ZNF695 in CESC single cells. ZNF695 expression was validated using GSE29570. ZNF695 was found to be aberrantly expressed in pan-cancer and CESC. There was a significant correlation observed between an elevated level of ZNF695 expression in patients with CESC and histological grade (p = 0.017). Furthermore, a strong association was found between high ZNF695 expression in CESC patients and poorer overall survival (OS) (HR: 1.87; 95% CI: 1.17-3.00; p = 0.009), Progression-free Survival (PFS) (HR: 1.86; 95% CI: 1.16-2.98; p = 0.010), and Disease-specific Survival (DSS) (HR: 1.98; 95% CI: 1.15-3.42; p = 0.014). The expression of ZNF695 in CESC patients (p = 0.006) was identified as an independent prognostic determinant. ZNF695 was associated with steroid hormone biosynthesis, oxidative phosphorylation, and so on. ZNF695 expression correlated with immune infiltration, immune score, and mRNAsi in CESC. ZNF695 expression significantly and negatively correlated with AICA ribonucleotide, BIX02189, QL-XI-92, STF-62247, and SNX-2112 in CESC. ZNF695 gene was upregulated in CESC tissues and cell lines. ZNF695 was significantly upregulated in the CESC cell lines. ZNF695 may be a potential prognostic biomarker and immunotherapeutic target for CESC patients.

Investigation of endoplasmic reticulum stress-regulated chaperones as biomarkers in idiopathic nonobstructive azoospermia.

Azoospermia is a condition in which sperm cells are completely absent in a male's ejaculate. Typically, sperm production occurs in the testes and is regulated by a complex series of cellular and molecular interactions. Endoplasmic reticulum (ER) stress arises when there is a deviation from or damage to the normal functions of the ER within cells. In response to this stress, a cascade of response mechanisms is activated to regulate ER stress within cells. This study aims to investigate the role of ERstress-regulated chaperones as potential biomarkers in male infertility. ER stress associated with azoospermia can manifest in cells such as spermatogonia in the testes and can impact sperm production. As a result of ER stress, the expression and activity of a variety of proteins within cells can be altered. Among these proteins are chaperone proteins that regulate the ER stress response. The sample size was calculated to be a minimum of 36 patients ineach group. In this preliminary study, we measured and compared serum levels of protein disulfide-isomerase A1, protein disulfide-isomerase A3 (PDIA3), mesencephalic astrocyte-derived neurotrophic factor (MANF), glucose regulatory protein 78 (GRP78), clusterin (CLU), calreticulin (CRT), and calnexin (CNX) between male subjects with idiopathic nonobstructive azoospermia and a control group of noninfertile males. Serum PDIA1 (P=0.0004), MANF (P=0.018), PDIA3 (P<0.0001), GRP78 (P=0.0027), andCRT (P=0.0009) levels were higher in the infertile group compared to the control. In summary, this study presents novel findings in a cohort of male infertile patients, emphasizing the significance of incorporating diverse biomarkers. It underscores the promising role of ER stress-regulated proteins as potential serum indicators for male infertility. By elucidating the impact of ER stress on spermatogenic cells, the research illuminates the maintenance or disruption of cellular health. A deeper understanding of these results could open the door to novel treatment approaches for reproductive conditions, including azoospermia.

CircRNAs as a novel class of potential diagnostic biomarkers in bipolar disorders.

Bipolar disorder (BD) is a severe mood disorder with uncertain causes and debilitating signs and symptoms. Gene expression is crucial to the pathophysiology of BD and could be influenced by genetic or epigenetic factors, by either direct modification of mRNA templates or by regulation of post-transcriptional translation. Recent evidence has shown that several critical processes in psychiatric diseases, such as neuronal activity or plasticity, synaptic transmission, and neuronal depolarization, have all been linked to circular RNAs (circRNAs). The circRNA profile of neuronal cells, which may be easily ascertained by a liquid biopsy, may shed light on the molecular pathophysiology of psychiatric disorders, including BD. This approach could aid in future development in diagnosis and treatment. In this review, we provide an in-depth understanding of the roles of circRNAs in the pathophysiology of BD and offer new insight into their potential as emerging diagnostic tools and therapeutic targets.

Adipose-tissue derived factors as potential biomarkers of cancer cachexia

Adipose-tissue derived factors as potential biomarkers of cancer cachexia

Circulating MicroRNA as a Potential Biomarker for Skeletal Disease in Primary Hyperparathyroidism: A Case-control Study.

The goal of this study was to characterize the microRNA (miRNA) expression signatures in patients with Primary hyperparathyroidism (PHPT) and identify miRNA biomarkers of bone homeostasis. PHPT is associated with increased bone turnover and decreased bone mass. miRNA are markers of bone remodeling. We performed a prospective case-control study of postmenopausal females with PHPT and control subjects matched for race, age, and bone mineral density (BMD). We collected clinical and biochemical data, assessed BMD by dual-energy x-ray absorptiometry, and measured 27 serum miRNAs related to bone remodeling. We used linear regression to assess the correlation between miRNA levels, conventional biochemical markers, and BMD. A total of 135 subjects were evaluated, including 49 with PHPT (discovery group), 47 control patients without PHPT, and an independent validation cohort of 39 PHPT patients. Of 27 miRNAs evaluated, 9 (miR-335-5p, miR-130b-3p, miR-125b-5p, miR-23a-3p, miR-152-3p, miR-582-5p, miR-144-5p, miR-320a, and miR-19b-3p) were differentially expressed in PHPT compared with matched control subjects. All 9 differentially expressed miRNAs significantly correlated with levels of serum parathyroid hormone (PTH), and 8 of the 9 correlated with calcium levels. No differentially expressed miRNAs were consistently correlated with markers of BMD. Subjects with PHPT segregate from controls based on the signature of these 9 miRNAs on principle component analysis. These data suggest that PHPT is characterized by a unique miRNA signature that is distinct from postmenopausal and idiopathic osteoporosis. Levels of specific miRNAs significantly correlate with PTH, suggesting that bone remodeling in PHPT may be mediated in part by PTH-induced changes in miRNA.

Inflammatory cytokines and their potential role in kidney stone disease: a Mendelian randomization study.

Previous studies have reported a complex relationship between inflammatory cytokines and kidney stone disease (KSD). The purpose of this paper is to investigate the potential causal impact of inflammatory cytokines on KSD by Mendelian randomization (MR) analysis. In our study, a thorough two-sample Mendelian randomization (MR) analysis was performed by us to determine the potential causal relationship between inflammatory cytokines and kidney stone disease. Utilizing GWAS summary data of inflammatory cytokines and KSD, we performed the first two-sample MR analysis. Genetic variants in GWASs related to inflammatory cytokines were employed as instrumental variables (IVs). The data on cytokines were derived from 14,824 participants and analyzed by utilizing the Olink Target-96 Inflammation Panel. GWAS summary data related to KSD (9713 cases and 366,693 controls) were obtained from the FinnGen consortium. The primary MR analysis method was Inverse variance weighted. Reverse MR analysis, Cochran's Q test, MR Egger, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used to assess the stability of the results. 91 cytokines were enrolled in the MR analysis after strict quality control of IV. The IVW analysis revealed 2 cytokines as risk factors for KSD: Cystatin D (OR 1.06, 95% CI 1.01-1.11), Fibroblast growth factor 5 (OR 1.06, 95% CI 1.00-1.12), suggesting they are positively associated with the occurrence of kidney stones. We also found 3 protective associations between cytokines and KSD: Artemin (OR 0.86, 95% CI 0.78-0.96), T-cell surface glycoprotein CD6 isoform (OR 0.92, 95% CI 0.88-0.98), STAM-binding protein (OR 0.83, 95% CI 0.69-0.99). There was no horizontal pleiotropy or significant heterogeneity in our MR analysis, as determined by the p-value results of our MR Egger's intercept test, Cochrane Q-test, and MR-PRESSO, which were all > 0.05. Our study explored a variety of inflammatory cytokines related to KSD through MR analysis, which validated several previous findings and provided some new potential biomarkers for KSD. However, the findings require further investigation to validate their exact functions in the pathogenesis and evolution of KSD.

The Indispensable Roles of GMDS and GMDS-AS1 in the Advancement of Cancer: Fucosylation, Signal Pathway and Molecular Pathogenesis.

Fucosylation is facilitated by converting GDP-mannose to GDP-4-keto-6-deoxymannose, which GDP-mannose 4,6-dehydratase, a crucial enzyme in the route, carries out. One of the most prevalent glycosylation alterations linked to cancer has reportedly been identified as fucosylation. There is mounting evidence that GMDS is intimately linked to the onset and spread of cancer. Furthermore, the significance of long-chain non-coding RNAs in the development and metastasis of cancer is becoming more well-recognized, and the regulatory mechanism of lncRNAs has emerged as a prominent area of study in the biological sciences. GMDS-AS1, an antisense RNA of GMDS, was discovered to have the potential to be an oncogene. We have acquired and analyzed relevant data to understand better how GMDS-AS1 and its lncRNA work physiologically and in tumorigenesis and progression. Additionally, we have looked into the possible effects of these molecules on cancer treatment approaches and patient outcomes. The physiological roles and putative processes of GMDS and lncRNA GMDS-AS1 throughout the development and progression of tumors have been assembled and examined. We also examined how these chemicals might affect patient prognosis and cancer therapy approaches. GMDS and GMDS-AS1 were determined to be research subjects by searching and gathering pertinent studies using the PubMed system. The analysis of these research articles demonstrated the close relationship between GMDS and GMDS-AS1 and tumorigenesis and the factors that influence them. GMDS plays a vital role in regulating fucosylation. The related antisense gene GMDS-AS1 affects the biological behaviors of cancer cells through multiple pathways, including the key processes of proliferation, migration, invasion, and apoptosis, providing potential biomarkers and therapeutic targets for cancer treatment and prognosis assessment.

Identifying and Evaluating Biological Markers of Postherpetic Neuralgia: A Comprehensive Review.

Postherpetic neuralgia (PHN) manifests as persistent chronic pain that emerges after a herpes zoster outbreak and greatly diminishes quality of life. Unfortunately, its treatment efficacy has remained elusive, with many therapeutic efforts yielding less than satisfactory results. The research to discern risk factors predicting the onset, trajectory, and prognosis of PHN has been extensive. However, these risk factors often present as nonspecific and diverse, indicating the need for more reliable, measurable, and objective detection methods. The exploration of potential biological markers, including hematological indices, pathological insights, and supportive tests, is increasing. This review highlights potential biomarkers that are instrumental for the diagnosis, management, and prognosis of PHN while also delving deeper into its genesis. Drawing from prior research, aspects such as immune responsiveness, neuronal injury, genetic makeup, cellular metabolism, and pain signal modulation have emerged as prospective biomarkers. The immune spectrum spans various cell subtypes, with an emphasis on T cells, interferons, interleukins, and other related cytokines. Studies on nerve injury are directed toward pain-related proteins and the density and health of epidermal nerve fibers. On the genetic and metabolic fronts, the focus lies in the detection of predisposition genes, atypical protein manifestations, and energy-processing dynamics, with a keen interest in vitamin metabolism. Tools such as functional magnetic resonance imaging, electromyography, and infrared imaging have come to the forefront in the pain signaling domain. This review compiles the evidence, potential clinical implications, and challenges associated with these promising biomarkers, paving the way for innovative strategies for predicting, diagnosing, and addressing PHN.

NMDAR1 autoantibodies as potential biomarkers for schizophrenia phenotyping

NMDAR1 autoantibodies as potential biomarkers for schizophrenia phenotyping

Integrating fecal metabolomics and gut microbiome to reveal the mechanism of Schisandra chinensis-Acorus tatarinowii Schott treatment in Alzheimer’s disease rats

BackgroundSchisandra chinensis (Turcz.) Baill (Schisandraceae) and Acorus tatarinowii Schott (Araceae Juss) (Sc-At) are two traditional Chinese medicinal herbs that are widely used in the treatment of neurological disorders such as insomnia. In our previous study, we found that Sc-At could improve the therapeutic efficacy of Alzheimer’s disease by affecting aromatase activity and estrogen levels, among other pathways. Material and methodsIn this study, first, the ameliorative effect of Sc-At on cognitive dysfunction in Alzheimer’s disease model rats was verified by Y-maze test together with Elisa assay. Second, fecal untargeted metabolomics analysis was performed using a UPLC-Q-TOF/MS-based metabolomics approach. 16S rDNA sequencing was utilized to screen the differential flora between groups, and linear discriminantan alysis effect size (LEfSe) was used to find the target flora. Finally, Spearman correlation analysis was combined to find the relationship between differential flora and differential metabolites in feces. Results(1) The results of Y-maze test and Elisa assay indicated that Sc-At could improve the cognitive dysfunction of AD model rats. (2) Metabolomics results showed that fecal metabolite levels were significantly different from those of rats in the blank group, and 18 potential biomarkers in feces were screened, mainly affecting linoleic acid metabolism, steroid hormone biosynthesis, sphingomyelin metabolism, riboflavin metabolism, etc. The 16S rDNA results showed that the abundance and diversity of intestinal flora in AD rats were destroyed, and the Sc-At treatment was able to reverse these changes. (3) Spearman’s correlation analysis showed a significant correlation between differential metabolites in feces and intestinal flora, further suggesting that Sc-At treats Alzheimer’s disease through the gut-brain axis. ConclusionsIn this study, we explored the mechanism of Sc-At in the treatment of Alzheimer’s disease by integrating fecal untargeted metabolomics and 16S rDNA gene sequencing, and the results showed that Sc-At exerts therapeutic effects on Alzheimer’s disease by improving the intestinal flora and related metabolic pathways.

LOX-Mediated ECM Mechanical Stress Induces Piezo1 Activation in Hypoxic-Ischemic Brain Damage and Identification of Novel Inhibitor of LOX

Hypoxic-ischemic encephalopathy (HIE) poses a significant challenge in neonatal medicine, often resulting in profound and lasting neurological deficits. Current therapeutic strategies for hypoxia-ischemia brain damage (HIBD) remain limited. Ferroptosis has been reported to play a crucial role in HIE and serves as a potential therapeutic target. However, the mechanisms underlying ferroptosis in HIBD remain largely unclear. In this study, we found that elevated lysyl oxidase (LOX) expression correlates closely with the severity of HIE, suggesting LOX as a potential biomarker for HIE. LOX expression levels and enzymatic activity were significantly increased in HI-induced neuronal models both in vitro and in vivo. Notably, we discovered that HI-induced brain tissue injury results in increased stiffness and observed a selective upregulation of the mechanosensitive ion channel Piezo1 in both brain tissue of HIBD and primary cortex neurons. Mechanistically, LOX increases its catalytic substrates, the Collagen I/III components, promoting extracellular matrix (ECM) remodeling and possibly mediating ECM cross-linking, which leads to increased stiffness at the site of injury and subsequent activation of the Piezo1 channel. Piezo1 senses these stiffness stimuli and then induces neuronal ferroptosis in a GPX4-dependent manner. Pharmacological inhibition of LOX or Piezo1 ameliorated brain neuronal ferroptosis and improved learning and memory impairments. Furthermore, we identified traumatic acid (TA) as a novel LOX inhibitor that effectively suppresses LOX enzymatic activity, mitigating neuronal ferroptosis and promoting synaptic plasticity. In conclusion, our findings elucidate a critical role for LOX-mediated ECM mechanical stress-induced Piezo1 activation in regulating ferroptotic cell death in HIBD. This mechanistic insight provides a basis for developing targeted therapies aimed at ameliorating neurological outcomes in neonates affected by HIBD.

Diagnostic and screening potential of plasma exosome miR‑99b‑5p and its combination with other miRNAs for colorectal cancer.

Extracellular vesicles (EVs) secreted by tumor cells have been documented to hold viable biomarker potential. Therefore, the present study evaluated the potential clinical value of EV-microRNAs (miRNAs or miRs) in the plasma exosomes of patients with colorectal cancer (CRC) for the early diagnosis and screening of CRC. In total, 95 plasma samples were collected at The Third Affiliated Hospital of Guangzhou Medical University (Guangzhou, China) between 2017 and 2019. Specifically, 68 samples were from patients with CRC and 27 were from healthy control (HC) donors. High-throughput sequencing was used to detect the expression of miRNAs in the isolated plasma EVs, which was subsequently verified by reverse transcription-quantitative PCR. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic potential of single and combined miRNAs for CRC. Bioinformatics analysis was employed to predict the target genes of candidate miRNAs. Compared with those in the HC group, the CRC group expressed higher levels of miR-99b-5p and miR-409-3p, especially during the early stages of CRC. Clinicopathological analysis confirmed the higher expression levels of miR-99b-5p during the early stages, as well as higher expression levels in the colon compared with those in the rectum. ROC curve analysis revealed that the area under the curve (AUC) of miR-99b-5p for the diagnosis of early CRC was 73.5% (P=0.007). The early diagnostic capability of miR-99b-5p combined with miR-409-3p for CRC was evaluated, and the AUC was found to be 74.1% (P=0.006). In addition, the AUC of the combination of miR-99b-5p, miR-409-3p and carcinoembryonic antigen was 81.2% (P<0.001), indicating that this three-parameter combination displayed higher diagnostic power compared with any single miRNA for early CRC screening. The results from the present study suggest that the expression of miR-99b-5p in plasma exosomes is significantly upregulated in CRC, which holds potential for the early diagnosis of this cancer type. Such potential can be enhanced further by combining it with other miRNAs. Therefore, the present study provides a comprehensive but preliminary insight for the viability of miR-99b-5p (alone or combined with other miRNAs) for CRC diagnosis, which requires further exploration in the future.

Low CD86 expression is a predictive biomarker for clinical response to the therapeutic HPV vaccine, IGMKK16E7: Results of a post-hoc analysis

Abstract Background Although therapeutic HPV vaccines could offer a non-invasive treatment for patients with cervical intraepithelial neoplasia (CIN), none have been clinically implemented. Oral administration of the therapeutic HPV vaccine, IGMKK16E7, results in the histological regression of HPV16-positive CIN2/3 to normal (complete response: CR). Here, we investigated biomarkers that could predict CR after oral administration of IGMKK16E7. Methods Forty-two patients administered with high-dose oral IGMKK16E7 in a Phase I/II trial were included. Cervical-exfoliated cells were collected before administration. Gene expression of CD4, CD8, Foxp3, PD-1, CTLA-4, CD103, CD28, CD80, CD86, and PD-L1 in the cells were measured by quantitative RT-PCR. ROC curve analysis and Mann-Whitney tests were used to explore potential biomarkers. Pearson correlation coefficient analysis was used to correlate gene expression profiles with clinical outcome. Results The only predictive biomarker of vaccine response for which ROC curve analysis showed significant diagnostic performance with histological CR was CD86 (AUC 0.71, 95%XI 0.53-0.88, p = .020). CR patients had significantly lower CD86 expression (CD86-low) than non-CR patients (p = .035). The CR rate for CD86-low and CD86-high cases was 50% and 19%, respectively, and CD86-low cases had a significantly higher CR rate (p = .047). Compared to all patients, the CD86-low group had a 1.5-fold increase in CR rate. Gene expression of CD86 and CTLA-4 showed the strongest positive correlation with clinical outcomes in the non-CR group (p &amp;lt; .001). Conclusion Low expression of CD86 in exfoliated cervical cells can be used as a pre-treatment biomarker to predict histological CR after IGMKK16E7 use.

Synovial Fluid White Blood Cell Count as a Potential Biomarker for the Clinical Severity of Knee Osteoarthritis: A Prospective Study

Knee osteoarthritis is categorized classically as a non-inflammatory arthropathy. However, there has been increasing evidence regarding the supplementary role of inflammation in the pathogenesis and disease progression of knee osteoarthritis. This study aims to identify a potential correlation between synovial fluid White Blood Cell (SF WBC) count and the severity of knee osteoarthritis clinical presentation. 200 knees (200 patients) were assessed through synovial fluid aspiration and cytology analysis for WBC count. All patients have filled out the Knee Injury and Osteoarthritis Outcome Score for clinical correlation. For the 200 knees, there was a statistically significant positive correlation between the severity of osteoarthritis clinical presentation as expressed by the KOOS and the synovial white blood cell count among the studied cases (p-value &lt; 0.001). There was no statistically significant correlation found between the patient’s age, sex, or side and KOOS or synovial fluid white cell count. The clinical severity of knee osteoarthritis is directly correlated with increased synovial fluid white cell count and hence, SF WBCs may play a role in identifying and grading osteoarthritis clinical severity. This may raise the interest in identifying the role of using specific disease-modifying drugs that deal with the WBC function in cases of osteoarthritis along with other modalities.

Identification of extracellular matrix proteins in plasma as a potential biomarker for intervertebral disc degeneration

Identification of extracellular matrix proteins in plasma as a potential biomarker for intervertebral disc degeneration

Circular RNA: The evolving potential in the disease world

Circular RNAs (circRNAs), a new star of noncoding RNAs, are a group of endogenous RNAs that form a covalently closed circle and occur widely in the mammalian genome. Most circRNAs are conserved throughout species and frequently show stage-specific expression during various stages of tissue development. CircRNAs were a mystery discovery, as they were initially believed to be a product of splicing errors; however, subsequent research has shown that circRNAs can perform various functions and help in the regulation of splicing and transcription, including playing a role as microRNA (miRNA) sponges. With the application of high throughput next-generation technologies, circRNA hotspots were discovered. There are emerging indications that explain the association of circRNAs with human diseases, like cancers, developmental disorders, and inflammation, and circRNAs may be a new potential biomarker for the diagnosis and treatment outcome of various diseases, including cancer. After the discoveries of miRNAs and long noncoding RNAs, circRNAs are now acting as a novel research entity of interest in the field of RNA disease biology. In this review, we aim to focus on major updates on the biogeny and metabolism of circRNAs, along with their possible/established roles in major human diseases.

Clinical value of peripheral blood miR-21 and miR-486 combined with CT forearly cancer diagnosis in pulmonary nodulessmoking

PurposeThis study aimed to investigate the clinical significance of combining peripheral blood miR-21 and miR-486 with CT for the early cancer diagnosis in pulmonary nodules.MethodsA total of 215 patients diagnosed with isolated pulmonary nodules with a history of smoking were selected as researchsubjects. 30 healthy volunteers with a history of smoking were recruitedas the control group.The selection of subjectswas based on the presence of isolated pulmonary nodules detected on chest CT scans. The training set consisted of 65 patients with lung nodules and 30 healthy smokers, while the verification setincluded 150 patients with lung nodules.ResultsCompared with the control group, the plasma expression level of miR-210 was significantly higher in the group of patients with benign pulmonary nodules (P < 0.05). The level of miR-486-5p was lower in patients with malignant pulmonary nodules compared to those with benign pulmonary nodules (P < 0.05). Moreover, the plasma level of miR-210was higher in patients with malignant pulmonary nodules compared to those with benign pulmonary nodules and healthy smokers (P < 0.05). The combination of miR-21 and miR-486 yielded an AUC of 0.865, which was significantly higher than any other gene combination (95%CI: 0.653–0.764, P < 0.05).ConclusionsThis study offered preliminary evidence supporting the use of peripheral blood miR-21 and miR-486, combined with CT scans, as potential biomarkers for the early cancer diagnosis in lung nodules.

Metabolomic characterization of COVID-19 survivors in Jilin province

BackgroundThe COVID-19 pandemic has escalated into a severe global public health crisis, with persistent sequelae observed in some patients post-discharge. However, metabolomic characterization of the reconvalescent remains unclear.MethodsIn this study, serum and urine samples from COVID-19 survivors (n = 16) and healthy subjects (n = 16) underwent testing via the non-targeted metabolomics approach using UPLC-MS/MS. Univariate and multivariate statistical analyses were conducted to delineate the separation between the two sample groups and identify differentially expressed metabolites. By integrating random forest and cluster analysis, potential biomarkers were screened, and the differential metabolites were subsequently subjected to KEGG pathway enrichment analysis.ResultsSignificant differences were observed in the serum and urine metabolic profiles between the two groups. In serum samples, 1187 metabolites were detected, with 874 identified as significant (457 up-regulated, 417 down-regulated); in urine samples, 960 metabolites were detected, with 39 deemed significant (12 up-regulated, 27 down-regulated). Eight potential biomarkers were identified, with KEGG analysis revealing significant enrichment in several metabolic pathways, including arginine biosynthesis.ConclusionsThis study offers an overview of the metabolic profiles in serum and urine of COVID-19 survivors, providing a reference for post-discharge monitoring and the prognosis of COVID-19 patients.

Glutamine metabolism-related genes predict the prognostic risk of acute myeloid leukemia and stratify patients by subtype analysis

BackgroundAcute myeloid leukemia (AML) is a genetically heterogeneous disease in which glutamine (Gln) contributes to AML progression. Therefore, this study aimed to identify potential prognostic biomarkers for AML based on Gln metabolism-related genes.MethodsGln-related genes that were differentially expressed between Cancer Genome Atlas-based AML and normal samples were analyzed using the limma package. Univariate, least absolute shrinkage, selection operators, and stepwise Cox regression analyses were used to identify prognostic signatures. Risk score-based prognostic and nomogram models were constructed to predict the prognostic risk of AML. Subsequently, consistent cluster analysis was performed to stratify patients into different subtypes, and subtype-related module genes were screened using weighted gene co-expression network analysis.ResultsThrough a series of regression analyses, HGF, ANGPTL3, MB, F2, CALR, EIF4EBP1, EPHX1, and PDHA1 were identified as potential prognostic biomarkers of AML. Prognostic and nomogram models constructed based on these genes could significantly differentiate between high- and low-risk AML with high predictive accuracy. The eight-signature also stratified patients with AML into two subtypes, among which Cluster 2 was prone to a high risk of AML prognosis. These two clusters exhibited different immune profiles. Of the subtype-related module genes, the HOXA and HOXB family genes may be genetic features of AML subtypes.ConclusionEight Gln metabolism-related genes were identified as potential biomarkers of AML to predict prognostic risk. The molecular subtypes clustered by these genes enabled prognostic risk stratification.