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Adenosine Triphosphate in Serum as a Promising Biomarker for Differential Diagnosis of Hepatitis B Disease Progression

ABSTRACT: The need to be diagnosed with liver biopsy makes the clinical progression of chronic HBV infection diagnosis a challenge. Existing HBV serum biochemical assays are used throughout clinical but have limited effects. Studies have shown that mitochondrial function is tightly coupled to HBV infection. Here, we verified the diagnostic value of serum Adenosine Triphosphate (ATP) as a potential marker for differential HBV infection progress by detecting the level of ATP in the serum from a wide spectrum of HBV-infected populations, and confirmed the role of ATP in the deterioration of HBV infection-related diseases through HBV-infected cells and mouse models. The results showed that there were significantly lower serum ATP levels in HBeAg-positive CHB patients compared with healthy controls. And during the progression of CHB to liver cirrhosis and hepatocellular carcinoma, the ATP level was increased but not higher than healthy controls. The area under the curve (AUC) of serum ATP was 0.9063 to distinguish HBeAg-positive CHB from healthy, and another AUC was 0.8328 in the CHB against the HCC group. Preliminary exploration of the mechanism indicated that the decline of serum ATP was due to impaired mitochondria in CHB patients. Our data provide evidence that serum ATP distinguishes the various progress of HBV infection-related diseases and expands diagnostic biomarkers for HBeAg-positive CHB patients with healthy controls.

SUBMITTER: Lin C

PROVIDER: S-EPMC9284211 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Monocyte distribution width as a promising biomarker for differential diagnosis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma.

Project description:ObjectiveWe aimed to investigate the association and diagnostic value of monocyte distribution width (MDW) for chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC).MethodsMDW levels were measured in 483 individuals (103 CHB, 77 LC, 153 HCC, and 150 controls). MDW was detected using UniCel Dx900 for specific cell volume parameters and the distribution of cell volumes.ResultsOur findings revealed a dynamic upward change in MDW levels across different stages of chronic liver disease, from CHB to LC and HCC. In CHB, MDW levels were highest among HBeAg-positive CHB patients and exhibited a negative correlation with HBV markers while positively correlating with ALT levels. In LC, MDW showed a positive association with the pathological progression of LC, demonstrating consistency with CP scores. MDW proved to be equally effective as traditional detection for diagnosing LC. In HCC, MDW was positively correlated with HCC occurrence and development, with higher levels observed in the high MDW group, which also exhibited elevated AFP levels, MELD scores, and 90-day mortality rates. MDW surpassed predictive models in its effectiveness for diagnosing HCC, as well as CHB and LC, with respective areas under the curve of 0.882, 0.978, and 0.973. Furthermore, MDW emerged as an independent predictor of HCC.ConclusionMDW holds significant diagnostic efficacy in identifying CHB, LC, and HCC. These findings suggest that MDW could serve as a promising biomarker for predicting the severity of liver diseases and aid in rational clinical treatment strategies.

| S-EPMC11251903 | biostudies-literature

Serum miRNA profile in diabetic patients with ischemic heart disease (IHD) as a promising non-invasive biomarker.

Project description:The aim of this study was to conduct a baseline comparison of serum-circulating miRNA in diabetic patients with and without ischemic heart disease. We analysed the expression levels of 798 serum miRNAs using the NanoString nCounter Technology Platform. The prediction of the putative miRNAs targets was performed by the Ingenuity Pathway Analysis (IPA) software. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of identified miRNAs. Our data showed that 6 miRNAs are significantly upregulated in type 2 diabetes mellitus (T2DM) patients with IHD compared to T2DM patients without IHD. Functional enrichment analysis of target genes by IPA showed networks and canonical pathways involved in the pathology of the cardiovascular system. All tested miRNAs showed high diagnostic value (AUC > 0.75).

2022-04-13 | GSE185845 | GEO

Serum DHCR24 Auto-antibody as a new Biomarker for Progression of Hepatitis C.

Project description:BackgroundNew biomarkers are needed to identify the stage of hepatitis C virus (HCV)-infected diseases in order to reduce the mortality rates. Herein, we investigated whether serum 3β-hydroxysterol Δ24-reductase antibody (DHCR24 Ab) may serve as a prognostic marker for hepatitis C infection progression to hepatocellular carcinoma (HCC).MethodsSerum DHCR24 Abs from 395 HCV-positive patients, including 133 chronic hepatitis (CHC), 85 liver cirrhosis (LCC), and 177 HCC (HCC-C) patients; 232 hepatitis B virus (HBV)-positive patients, including 103 chronic hepatitis (CHB), 56 liver cirrhosis (LCB), and 73 HCC (HCC-B) patients; and 24 healthy controls, were measured using enzyme-linked immunosorbent assay.ResultsThe serum DHCR24 Ab levels were significantly higher in patients with CHC than in healthy controls, in LCC than in CHC, and in LCC than in HCC-C (P < 0.0001 for all). The concentration of serum DHCR24 Ab in HCC-B patients showed no significant difference compared to CHB and LCB patients (P = 0.1247). The DHCR24 Ab levels were significantly higher in early HCC-C than CHC or LCC patients and in late HCC-C compared to early HCC-C patients. The sensitivity of the DHCR24 Ab for HCC-C detection (70.6%) was higher than that of alpha-fetoprotein (AFP; 54.8%) and protein induced by vitamin K absence or antagonist-II (PIVKA-II; 42 · 5%). Moreover, DHCR24 was up-regulated in HCV-positive, but not HBV-positive tissues or HBV-negative, HCV-negative HCC specimens.ConclusionsDHCR24 auto-antibody represents a potential noninvasive biomarker for HCV-related liver disease and may facilitate the diagnosis of PIVKA-II and AFP-negative HCC.

| S-EPMC4535309 | biostudies-literature

Adenosine Triphosphate-Sensitive Potassium Currents in Heart Disease and Cardioprotection.

Project description:The subunit makeup of the family of adenosine triphosphate-sensitive potassium channel (KATP) channels is more complex and labile than thought. The growing association of Kir6.1 and SUR2 variants with specific cardiovascular electrical and contractile derangements and the clear association with Cantu syndrome establish the importance of appropriate activity in normal function of the heart and vasculature. Further studies of such patients will reveal new mutations in KATP subunits and perhaps in proteins that regulate KATP synthesis, trafficking, or location, all of which may ultimately benefit therapeutically from the unique pharmacology of KATP channels.

| S-EPMC4894346 | biostudies-literature

Identification of a serum biomarker panel for the differential diagnosis of cholangiocarcinoma and primary sclerosing cholangitis.

Project description:The non-invasive differentiation of malignant and benign biliary disease is a clinical challenge. Carbohydrate antigen 19-9 (CA19-9), leucine-rich α2-glycoprotein (LRG1), interleukin 6 (IL6), pyruvate kinase M2 (PKM2), cytokeratin 19 fragment (CYFRA21.1) and mucin 5AC (MUC5AC) have reported utility for differentiating cholangiocarcinoma (CCA) from benign biliary disease. Herein, serum levels of these markers were tested in 66 cases of CCA and 62 cases of primary sclerosing cholangitis (PSC) and compared with markers of liver function and inflammation. Markers panels were assessed for their ability to discriminate malignant and benign disease. Several of the markers were also assessed in pre-diagnosis biliary tract cancer (BTC) samples with performances evaluated at different times prior to diagnosis. We show that LRG1 and IL6 were unable to accurately distinguish CCA from PSC, whereas CA19-9, PKM2, CYFRA21.1 and MUC5AC were significantly elevated in malignancy. Area under the receiver operating characteristic curves for these individual markers ranged from 0.73-0.84, with the best single marker (PKM2) providing 61% sensitivity at 90% specificity. A panel combining PKM2, CYFRA21.1 and MUC5AC gave 76% sensitivity at 90% specificity, which increased to 82% sensitivity by adding gamma-glutamyltransferase (GGT). In the pre-diagnosis setting, LRG1, IL6 and PKM2 were poor predictors of BTC, whilst CA19-9 and C-reactive protein were elevated up to 2 years before diagnosis. In conclusion, LRG1, IL6 and PKM2 were not useful for early detection of BTC, whilst a model combining PKM2, CYFRA21.1, MUC5AC and GGT was beneficial in differentiating malignant from benign biliary disease, warranting validation in a prospective trial.

| S-EPMC5915126 | biostudies-literature

Transition State Analysis of Adenosine Triphosphate Phosphoribosyltransferase.

Project description:Adenosine triphosphate phosphoribosyltransferase (ATP-PRT) catalyzes the first step in histidine biosynthesis, a pathway essential to microorganisms and a validated target for antimicrobial drug design. The ATP-PRT enzyme catalyzes the reversible substitution reaction between phosphoribosyl pyrophosphate and ATP. The enzyme exists in two structurally distinct forms, a short- and a long-form enzyme. These forms share a catalytic core dimer but bear completely different allosteric domains and thus distinct quaternary assemblies. Understanding enzymatic transition states can provide essential information on the reaction mechanisms and insight into how differences in domain structure influence the reaction chemistry, as well as providing a template for inhibitor design. In this study, the transition state structures for ATP-PRT enzymes from Campylobacter jejuni and Mycobacterium tuberculosis (long-form enzymes) and from Lactococcus lactis (short-form) were determined and compared. Intrinsic kinetic isotope effects (KIEs) were obtained at reaction sensitive positions for the reverse reaction using phosphonoacetic acid, an alternative substrate to the natural substrate pyrophosphate. The experimental KIEs demonstrated mechanistic similarities between the three enzymes and provided experimental boundaries for quantum chemical calculations to characterize the transition states. Predicted transition state structures support a dissociative reaction mechanism with a DN*AN‡ transition state. Weak interactions from the incoming nucleophile and a fully dissociated ATP adenine are predicted regardless of the difference in overall structure and quaternary assembly. These studies establish that despite significant differences in the quaternary assembly and regulatory machinery between ATP-PRT enzymes from different sources, the reaction chemistry and catalytic mechanism are conserved.

| S-EPMC6693643 | biostudies-literature

Serum miRNA Profile in Diabetic Patients With Ischemic Heart Disease as a Promising Non-Invasive Biomarker.

Project description:The increasing morbidity and mortality of type 2 diabetic mellitus (T2DM) patients with ischemic heart disease (IHD) highlight an urgent need to identify early biomarkers, which would help to predict individual risk of development of IHD. Here, we postulate that circulating serum-derived micro RNAs (miRNAs) may serve as potential biomarkers for early IHD diagnosis and support the identification of diabetic individuals with a predisposition to undergo IHD. We obtained serum samples from T2DM patients either with IHD or IHD-free and analysed the expression levels of 798 miRNAs using the NanoString nCounter technology platform. The prediction of the putative miRNAs targets was performed using the Ingenuity Pathway Analysis (IPA) software. Gene Ontology (GO) analysis was used to identify the biological function and signalling pathways associated with miRNA target genes. Hub genes of protein-protein interaction (PPI) network were identified by STRING database and Cytotoscape tool. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of identified miRNAs. Real-time quantitative polymerase chain reaction (qRT-PCR) was used for nCounter platform data validation. Our data showed that six miRNAs (miR-615-3p, miR-3147, miR-1224-5p, miR-5196-3p, miR-6732-3p, and miR-548b-3p) were significantly upregulated in T2DM IHD patients compared to T2DM patients without IHD. Further analysis indicated that 489 putative target genes mainly affected the endothelin-1 signalling pathway, glucocorticoid biosynthesis, and apelin cardiomyocyte signalling pathway. All tested miRNAs showed high diagnostic value (AUC = 0.779 - 0.877). Taken together, our research suggests that circulating miRNAs might have a crucial role in the development of IHD in diabetic patients and may be used as a potential biomarker for early diagnosis.

| S-EPMC9157821 | biostudies-literature

CPA4 is a promising diagnostic serum biomarker for pancreatic cancer.

Project description:CPA4 belongs to a member of the metallocarboxypeptidase family, and its expression in pancreatic cancer samples and clinical significance are still not investigated until now. In this study, we aimed to evaluate the level of CPA4 in pancreatic cancer samples and study its clinical implications as a diagnostic marker for pancreatic cancer. The levels of CPA4 in pancreatic cancer tissues and serum samples were measured by immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA), respectively. Among 150 pancreatic cancer tissues examined, 86.7% (130/150) of cases showed positive staining for CPA4. Clinicopathological relevance analysis showed that CPA4 expression was correlated with advanced clinical stage and lymph node metastasis. Also, we found that the levels of CPA4 in serum samples were significantly high in cases whose expression was also high in paired tissue samples (N=50). In a larger sample set, we found that serum CPA4 in pancreatic cancer patients was significantly higher than for healthy controls (P<0.05). In addition, high serum CPA4 was significantly associated with the TNM stage, Lymph node involvement and distant metastasis. At a cutoff value of 0.3 ng/ml, CPA4 might be a better diagnostic biomarker of pancreatic cancer than CA199. In conclusion, CPA4 overexpression is associated with pancreatic cancer progression, and it might be a potential diagnostic serum marker for pancreatic cancer.

| S-EPMC4759400 | biostudies-literature

Potential Biomarkers for Diagnosis of Overactive Bladder Patients: Urinary Nerve Growth Factor, Prostaglandin E2, and Adenosine Triphosphate.

Project description:PURPOSE:This study aimed to investigate potential biomarkers for the diagnosis of overactive bladder (OAB). METHODS:A total of 219 subjects were enrolled and divided into 2 groups: OAB subjects (n=189) and controls without OAB symptoms (n=30). Three-day voiding diaries and questionnaires were collected, and urinary levels of nerve growth factor (NGF), prostaglandin E2, and adenosine triphosphate were measured and normalized to urine creatinine (Cr). Baseline characteristics and urinary levels of markers were analyzed. A receiver-operator characteristic (ROC) curve was used to analyze the diagnostic performance of urinary markers. Urinary levels of markers according to subgroup and pathogenesis of OAB were evaluated. Correlation analyses were used to analyze the relationship between urinary levels of markers and voiding diary parameters and questionnaires. RESULTS:There was no difference between the 2 groups with regards to age, sex ratio, or urine Cr (P>0.05). The urinary levels of NGF/Cr were higher in OAB subjects than in controls (P<0.001). Urinary NGF/Cr was a sensitive biomarker for discriminating OAB patients (area under the curve=0.741; 95% confidence interval, 0.62-0.79; P=0.001) in the ROC curve. The urinary levels of NGF/Cr were significantly higher in OAB subjects than in controls regardless of subgroup or pathogenesis. Correlation analysis demonstrated urinary urgency was significantly related to urinary NGF/Cr level (correlation coefficient, 0.156). Limitations include a relatively wide variation of urinary markers. CONCLUSIONS:Urinary NGF is a potential biomarker that could serve as a basis for adjunct diagnosis of OAB.

| S-EPMC5636954 | biostudies-literature

Serum IL-18 Is a Potential Biomarker for Predicting Severe Dengue Disease Progression

Project description:Background. Dengue virus (DENV) infection is the most common arboviral disease that affects tropical and subtropical regions. Based on the clinical hallmarks, the different severities of patients range from mild dengue fever (MDF) to severe dengue diseases (SDDs) and include dengue hemorrhagic fever or dengue shock syndrome. These are commonly associated with cytokine release syndrome (CRS). The types and levels of cytokines/chemokines, which are suppressed or enhanced, are varied, indicating CRS's pathogenic and host defensive effects. Principal Finding. In this study, we created an integrated and precise multiplex panel of cytokine/chemokine assays based on our literature analysis to monitor dengue CRS. A 24-plex panel of cytokines/chemokines was evaluated to measure the plasma levels of targeting factors in dengue patients with an MDF and SDD diagnosis without or with comorbidities. As identified in sixteen kinds of cytokines/chemokines, ten were significantly (P < 0.05) (10/16) increased, one was significantly (P < 0.01) (1/16) decreased, and five were potentially (5/16) altered in all dengue patients (n = 30) in the acute phase of disease onset. Compared to MDF, the levels of IL-8 (CXCL-8) and IL-18 in SDD were markedly (P < 0.05) increased, accompanied by positively increased IL-6 and TNF-α and decreased IFN-γ and RANTES. With comorbidities, SDD significantly (P < 0.01) portrayed elevated IL-18 accompanied by increased IL-6 and decreased IFN-α2 and IL-12. In addition, decreased platelets were significantly (P < 0.05) associated with increased IL-18. Significance. These results demonstrate an efficient panel of dengue cytokine/chemokine assays used to explore the possible level of CRS during the acute phase of disease onset; also, we are the first to report the increase of IL-18 in severe dengue with comorbidity compared to severe dengue without comorbidity and mild dengue.

| S-EPMC8560270 | biostudies-literature

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