Potential Biomarkers For Early Diagnosis Research Articles

Potential Biomarkers for Early Diagnosis, Evaluation, and Prognosis of Sepsis-Induced Coagulopathy.

Sepsis-induced coagulopathy (SIC) is a life-threatening complication characterized by the systemic activation of coagulation in sepsis. The diagnostic criteria of SIC consist of three items, including Sequential Organ Failure Assessment (SOFA) score, platelet count, and prothrombin time (PT)-international normalized ratio (INR). SIC has a high prevalence and it can lead to a higher mortality rate and longer length of hospital and ICU stay. Thus, the early detection of SIC is extremely important. It is unfortunate that there is still no precise biomarker for early diagnosis and assessment of the prognosis of SIC. We reviewed the current literature and discovered that some potential biomarkers, such as soluble thrombomodulin (sTM), thrombin-antithrombin complex (TAT), tissue plasminogen activator-inhibitor complex (t-PAIC), α2-plasmin inhibitor-plasmin complex (PIC), C-type lectin-like receptor 2 (CLEC-2), neutrophil extracellular traps (NETs), prothrombin fragment 1.2 (F1.2), Angiopoietin-2 (Ang-2), plasminogen activator inhibitor-1 (PAI-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) may be useful for early diagnosis, evaluation, and prognosis of SIC. Early initiation of treatment without missing any therapeutic opportunities may improve SIC patients' prognosis. Further large-scale clinical studies are still needed to confirm the role of these biomarkers in the diagnosis and prognosis assessment of SIC.

Diet-mediated gut microbial community modulation and signature metabolites as potential biomarkers for early diagnosis, prognosis, prevention and stage-specific treatment of colorectal cancer

BackgroundOver the last decade, studies have shown an increased incidence of colorectal cancer (CRC), particularly early onset colorectal cancer (EOCRC). Researchers have demonstrated that dietary behavior, especially among young adults, influences alterations in the gut microbial community, leading to an increased accumulation of pathogenic gut microbiota and a decrease in beneficial ones. Unfortunately, CRC is likely to be diagnosed at a late stage, increasing CRC-related mortality. However, this alteration in the gut microbiota (gut dysbiosis) can be harnessed as a biomarker for non-invasive diagnosis, prognosis, prevention, and treatment of CRC in an effort to prevent late diagnosis and poor prognosis associated with CRC. Aim of reviewThis review discusses identification of potential biomarkers by targeting diet-mediated gut dysbiosis for the stage-specific diagnosis, prognosis, treatment, and prevention of CRC. Our findings provide a comprehensive insight into the potential of protumorigenic bacteria (e.g.pathogenic Escherichia coli,enterotoxigenic Bacteroides fragilis and Fusobacterium nucleatum) and their metabolites (e.g., colibactin and B. fragilis toxin) from gut dysbiosis as biomarkers for the diagnosis of CRC. Key scientific concepts of reviewCollectively, a detailed understanding of the available data from current studies suggests that, further research on quantification of metabolites and stage-specific pathogenic microbial abundance is required for the diagnosis and treatment of CRC based on microbial dysbiosis. Specifically, future studies on faecal samples, from patient with CRC, should be conducted for F. nucleatum among different opportunistic bacteria, given its repeated occurrence in faecal samples and CRC biopsies in numerous studies. Finally, we discuss the potential of faecal microbial transplantation (FMT) as an intervention to restore damaged gut microbiota during CRC treatment and management.

Immune disturbances in female genital tuberculosis and latent genital tuberculosis.

Female genital tuberculosis (FGTB), an important clinical sub-type of extra-pulmonary tuberculosis (EPTB) is responsible for about 10% cases of infertility in India. Both FGTB and latent genital tuberculosis (LGTB) can cause infertility through blockage of fallopian tubes and through altered uterine endometrial receptivity. This review tries to elucidates the role of various immune factors in FGTB and LGTB. Various immune disturbances are observed in FGTB and LGTB like growth factors and cytokines which inhibit implantation and several inflammatory signaling pathways like mitogen activated protein kinase (MAPK), natural killer (NK) cells, nuclear factor kappa-B (NF-KB), tumor necrosis factor (TNF), and toll like receptors (TLR) signaling are dysregulated. These altered immune factors and pathways may be detected in the endometrial biopsies at the early stages of disease before permanent damage. Prompt and adequate treatment with the four anti-tubercular drugs (rifampicin [R], isoniazid [H], pyrazinamide [Z], and ethambutol [E]) can increase pregnancy rates in some of these women. Assisted reproduction especially in-vitro fertilization and embryo transfer may be required for some women. Inflammatory pathways identified from the gene profiling have enabled development of potential biomarkers for early diagnosis of FGTB. Immunomodulation and novel biotechniques like stem cell transplantation, nanoparticles and host directed therapies are being tried in selected patients of FGTB and LGTB with promising results.

Identification of serum MiRNAs as candidate biomarkers for non-small cell lung cancer diagnosis

BackgroundLung cancer is one of the most common solid tumors worldwide and the leading cause of cancer-associated death. Non-small cell lung cancer (NSCLC) is accounts for approximately 85% of all the lung cancers and lung squamous carcinoma (SCC) and adenocarcinoma (ADC) are the main subtypes of NSCLC. Early diagnose using serum biomarkers could improve the overall survival of patients. In this study, we aimed to identify miRNAs from serum with clinical utility in the diagnosis of NSCLC.MethodsTen patients with SCC, ten patients with ADC and five noncancerous individuals were enrolled in the screening cohort. miRNA expression levels in serum were measured by microarray analysis. Candidate miRNAs were validated by real-time quantitative polymerase chain reaction analysis in a validation cohort of 78 NSCLC patients and 44 noncancerous individuals. Receiver operating characteristic curves were used to assess the diagnostic performance of serum miRNAs for NSCLC. Logistic regression was used to evaluate the diagnostic value of the combination of markers.ResultsSix candidate miRNAs were differentially expressed between NSCLC patients and noncancerous individuals in the screening set (fold change > 2, p < 0.05). Among them, expression levels of miR-3149 and miR-4769.3p were confirmed to be significantly increased in tumor serum in the validation set. The area under the curve values of miR-3149 and miR-4769.3p in distinguishing NSCLC patients from noncancerous controls were 0.830 and 0.735, respectively. When combined with tumor markers CEA and Cyfra21-1, the joint diagnostic model increased the area under the curve to 0.898.ConclusionSerum miRNAs miR-3149 and miR-4769.3p were up-regulated in NSCLC and may be potential biomarkers for early diagnosis of lung cancer.

Long non-coding RNA H19: a potential biomarker and therapeutic target in human malignant tumors.

Long non-coding RNAs play important roles in cellular functions and disease development. H19, as a long non-coding RNA, is pervasively over-expressed in almost all kinds of human malignant tumors. Although many studies have reported that H19 is closely associated with tumor cell proliferation, apoptosis, invasion, metastasis, and chemoresistance, the role and mechanism of H19 in gene regulation and tumor development are largely unclear. In this review, we summarized the recent progress in the study of the major functions and mechanisms of H19 lncRNA in cancer development and progression. H19 possesses both oncogenic and tumor-suppressing activities, presumably through regulating target gene transcription, mRNA stability and splicing, and competitive inhibition of endogenous RNA degradation. Studies indicate that H19 may involve in cell proliferation and apoptosis, tumor initiation, migration, invasion, metastasis and chemoresistance and may serve as a potential biomarker for early diagnosis, prognosis, and novel molecular target for cancer therapy.

Gene expression profile analysis to discover molecular signatures for early diagnosis and therapies of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer (BC), and it accounts for approximately 10%-20% of all invasive BCs diagnosed worldwide. The survival rate of TNBC in stages III and IV is very low, and a large number of patients are diagnosed in these stages. Therefore, the purpose of this study was to identify TNBC-causing molecular signatures and anti-TNBC drug agents for early diagnosis and therapies. Five microarray datasets that contained 304 TNBC and 109 control samples were collected from the Gene Expression Omnibus (GEO) database, and RNA-Seq data with 116 tumor and 124 normal samples were collected from TCGA database to identify differentially expressed genes (DEGs) between TNBC and control samples. A total of 64 DEGs were identified, of which 29 were upregulated and 35 were downregulated, by using the statistical limma R-package. Among them, seven key genes (KGs) were commonly selected from microarray and RNA-Seq data based on the high degree of connectivity through PPI (protein-protein interaction) and module analysis. Out of these seven KGs, sixKGs (TOP2A, BIRC5, AURKB, ACTB, ASPM, and BUB1B) were upregulated and one (EGFR) was downregulated. We also investigated their differential expression patterns with different subtypes and progression stages of BC by the independent datasets of RNA-seq profiles from UALCAN database, which indicated that they may be potential biomarkers for early diagnosis. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses with the proposed DEGs were performed using the online Enrichr database to investigate the pathogenetic processes of TNBC highlighting KGs. Then, we performed gene regulatory network analysis and identified three transcriptional (SOX2, E2F4, and KDM5B) and three post-transcriptional (hsa-mir-1-3p, hsa-mir-124-3p, and hsa-mir-34a-5p) regulators of KGs. Finally, we proposed five KG-guided repurposable drug molecules (imatinib, regorafenib, pazopanib, teniposide, and dexrazoxane) for TNBC through network pharmacology and molecular docking analyses. These drug molecules also showed significant binding performance with some cancer-related PTM-sites (phosphorylation, succinylation, and ubiquitination) of top-ranked four key proteins (EGFR, AURKB, BIRC5, and TOP2A). Therefore, the findings of this computational study may play a vital role in early diagnosis and therapies against TNBC by wet-lab validation.

Dysregulated RUNX1 Predicts Poor Prognosis by Mediating Epithelialmesenchymal Transition in Cervical Cancer.

Runt-related transcription factor 1 (RUNX1) has been proven to be over-expressed and vital in many malignancies. However, its role in cervical cancer is still unclear. Some online databases (Oncomine, GEPIA, UALCAN, LinkedOmics, and others) were used to explore the expression level, prognostic significance, and gene mutation characteristics of RUNX1 in cervical cancer. The protein levels of RUNX1 in cervical cancer were measured by immunohistochemistry (IHC). The functional changes of cervical cancer cells were measured in vitro after decreasing RUNX1. Bioinformatic results revealed that RUNX1 was upregulated in cervical cancer compared to normal tissues. Moreover, over-expression of RUNX1 was significantly correlated with cervical cancer patients' clinical parameters (e.g., individual cancer stages, patients' age, nodal metastasis status, and others). Meanwhile, functional enrichment analysis of RUNX1-related genes indicated that RUNX1 was mainly involved in the epithelial-mesenchymal transition (EMT) process in cervical cancer. Furthermore, RUNX1 may be upregulated by hsamiR-616-5p and hsa-miR-766 identified by miRDB, TargetScan, and miRWalk. Finally, RUNX1 was upregulated in cervical cancer compared to normal tissues by IHC in collected cervical cancer samples. The invasion and migration abilities of cervical cancer cells were significantly reduced by repressing EMT after knocking down RUNX1 in vitro. RUNX1 was highly expressed in cervical cancer, and upregulated RUNX1 could significantly promote the invasive abilities of cervical cancer cells by inducing EMT. Therefore, RUNX1 may be a potential biomarker for early diagnosis and targeted therapy of cervical cancer.

Growth performance, digestibility, and plasma metabolomic profiles of Saanen goats exposed to different doses of aflatoxin B1.

Aflatoxin contamination of feed poses a great risk to the global dairy industry. Analyzing the aflatoxin B1 (AFB1)-induced metabonomic changes in ruminants and screening potential biomarkers for early diagnosis of AFB1 exposure is urgently needed. Here, the effects of different doses (0, 50, and 500 μg/kg of the diet, dry matter basis) of AFB1 exposure on digestibility and performance of Saanen goats were studied, and a comprehensive untargeted metabolomic analysis was performed to reveal plasma metabonomic changes caused by the AFB1 exposure. In the current study, AFB1 exposure decreased total-tract nutrient digestibilities, nitrogen retention, total weight gain, and average daily gain of Saanen goats in a dose-dependent manner. Untargeted metabolomics revealed alterations in the plasma metabolome. A total of 3,310 and 1,462 ion peaks were obtained in positive and negative ion modes, respectively. Based on the screening criteria, 1,338 differential metabolites were detected between control and low-dose AFB1 (50 μg/kg) groups, 1,358 metabolites differed between control and high-dose AFB1 (500 μg/kg) groups, and 58 metabolites differed among all groups. Pathway analyses showed that choline metabolism in cancer and glycerophospholipid metabolism were significantly affected by the AFB1 treatments. Moreover, dysregulation of amino acid metabolism was also observed in AFB1 treated goats. The findings provided novel insights into the toxicity of AFB1 in ruminants. Exploring the underlying molecular causes of the changes may help the development of rapid diagnostic techniques and effective interventions for AFB1 intoxication.

Differential Expression of Serum Proteins in Chronic Obstructive Pulmonary Disease Assessed Using Label-Free Proteomics and Bioinformatics Analyses.

As a common respiratory disease, chronic obstructive pulmonary disease (COPD) has a high morbidity and mortality. Current clinical therapies are not ideal and do not improve lung function or long-term life quality. It is very important to find new potential pathogenic mechanisms, biomarkers, and targets with therapeutic value in COPD. Serum samples collected from acute exacerbation and stable COPD and healthy participants were analyzed using label-free liquid chromatography tandem mass spectrometry to identify the differentially expressed proteins (DEPs) between two groups. Bioinformatics analyses were performed to determine the biological processes associated with those DEPs. Key proteins were validated by enzyme linked immunosorbent assay (ELISA). In total, 661 proteins were detected in serum from patients with COPD and healthy participants. Compared with healthy participants, patients with acute exacerbation of COPD had 45 DEPs, 13 were upregulated and 32 were downregulated; and patients with stable COPD had 79 DEPs, 18 were upregulated and 61 were downregulated. Gene Ontology functional annotation results indicated that the DEPs identified in patients with COPD were associated with the terms cellular anatomical entity, binding, and cellular process. Kyoto Encyclopedia of Genes and Genomes functional annotation analysis and the Clusters of Orthologous Genes database analysis indicated that the functions of these DEPs were primarily in signal transduction mechanisms and amino acid transport and metabolism. The ELISA results for three key proteins of IGFBP2, LRG1 and TAGLN were consistent with the LC-MS/MS results and the area under the receiver operating characteristic of the combined index was 0.893 (95% CI: 0.813, 0.974). Our findings suggested pathogenic mechanisms underlying COPD stages and indicated three key proteins that may warrant further study as potential biomarkers for early diagnosis or prognosis of COPD or as therapeutic targets.

Downregulation of miR-125a-5p Leads to STAT3 Increased Expression in Breast Cancer Patients.

Breast cancer (BC) is one of the main causes of cancer-related death in women worldwide. It is necessary to find methods for prognosis and early detection of BC. MicroRNAs inhibit the expression of special target genes at the post-transcriptional stage and have a fundamental role in various cancers. They function as oncogenes or tumor suppressors. MiR-125a- 5p acts as a tumor suppressor in some cancers through a signal transducer and activator of transcription 3 (STAT3) suppression. STAT3 is activated in response to cytokines and growth factors, affecting the transcription of target genes. We examined the association between miR-125a-5p and STAT3 expression levels in breast cancer patients for the first time through a case-control study on an Iranian population. Total RNAs were extracted from breast cancer and healthy tissues using TRIzol Reagent. Complementary DNA synthesis was performed, and Real-time PCR was done using miR-125a and STAT3-specific primers. GAPDH and U48 genes were used as internal controls. Statistical analysis of the results was conducted by SPSS v.19.0 software. We obtained a significant association between miR-125a-5p down-regulation and breast cancer disease (0.4333 in patients vs. 1.656 in controls, p-value = 0.009). STAT3 expression was significantly up-regulated in BC samples relative to healthy subjects (1.324 vs. 0.6557, respectively) and p-value <0.0001. We investigated that decreased miR-125a-5p expression levels were significantly associated with increased STAT3 expression in BC tissues. Therefore, the expression changes of miR- 125a-5p can be an important potential biomarker for early diagnosis of breast cancer. Also, the miRNA molecule may have serious therapeutic potential.

Plasma SNORD42B and SNORD111 as potential biomarkers for early diagnosis of non-small cell lung cancer.

Non-small-cell lung cancer (NSCLC) still occupied the leading reason of cancer death due to lack of availability of early detection. This study aimed to identify the effective biomarkers for the early-stage NSCLC diagnostics based on plasma snoRNAs. The differential snoRNAs between lung cancer patients and healthy donors were analyzed using the SNORic and TCGA databases. SNORD42B and SNORD111 were screened out and further verified in 48 FFPE NSCLC and adjacent normal tissues, as well as in plasma from 165 NSCLC patients and 118 health donors using qRT-PCR. Next, their diagnostic efficiency, as well as combined with carcinoembryonic antigen (CEA), was obtained by the analysis of receiver operating characteristic (ROC). We first screened out 47 top differential snoRNAs, among which the top 10 upregulated snoRNAs in LUAD were U44, U75, U78, U77, SNORD72, SNORD13, SNORD12B, SCARNA5, U80, SNORD41, and in LUSC were U44, U75, U78, SNORD41, SNORD111, SNORA56, U17a, SNORD35A, SNORD32A, SNORA71D. SNORD42B and SNORD111 was significantly increased not only in tumor tissues but also in plasma from NSCLC and early-stage NSCLC patients. They were capable to act as promising biomarkers for NSCLC and early-stage NSCLC diagnosis. Moreover, CEA diagnostic efficiency for early-stage NSCLC was significantly improved when combined with these two plasma snoRNAs. SNORD42B and SNORD111 could act as the potential and non-invasive diagnostic biomarkers for NSCLC and early-stage NSCLC.

MicroRNAs Dysregulation as Potential Biomarkers for Early Diagnosis of Endometriosis.

Endometriosis is a benign chronic disease in women that is characterized by the presence of active foci of the endometrium or endometrial tissue occurring outside of the uterus. The disease causes disabling symptoms such as pelvic pain and infertility, which negatively affect a patient’s quality of life. In addition, endometriosis imposes an immense financial burden on the healthcare system. At present, laparoscopy is the gold standard for diagnosing the disease because other non-invasive diagnostic tests have less accuracy. In addition, other diagnostic tests have low accuracy. Therefore, there is an urgent need for the development of a highly sensitive, more specific, and non-invasive test for the early diagnosis of endometriosis. Numerous researchers have suggested miRNAs as potential biomarkers for endometriosis diagnosis due to their specificity and stability. However, the greatest prognostic force is the determination of several miRNAs, the expression of which varies in a given disease. Despite the identification of several miRNAs, the studies are investigatory in nature, and there is no consensus on them. In the present review, we first provide an introduction to the dysregulation of miRNAs in patients with endometriosis and the potential use of miRNAs as biomarkers in the detection of endometriosis. Then we will describe the role of the mir-200 family in endometriosis. Several studies have shown that the expression of the mir-200 family changes in endometriosis patients, suggesting that they could be used as a diagnostic biomarker and therapeutic target for endometriosis.

Proteomic profiling and correlations with clinical features reveal biomarkers indicative of diabetic retinopathy with diabetic kidney disease.

Diabetic retinopathy (DR) and diabetic kidney disease (DKD) are complications of diabetes and place serious health and economic burdens on society. However, the identification and characterization of early biomarkers for DKD, especially for nonproliferative DR (NPDR) patients with DKD, are still needed. This study aimed to demonstrate the plasma proteomic profiles of NPDR+DKD and NPDR patients and identify potential biomarkers for early diagnosis of DKD. Fifteen plasma samples from the NPDR group and nine from the NPDR+DKD group were analyzed by LC−MS/MS to identify the differentially expressed proteins between the two groups. Functional enrichment, protein−protein interaction and clinical feature correlation analyses revealed the target protein candidates, which were verified using ELISA and receiver operating characteristic (ROC) analysis. In total, 410 proteins were detected in plasma; 15 were significantly upregulated and 7 were downregulated in the NPDR+DKD group. Bioinformatics analysis suggested that DKD is closely related to cell adhesion and immunity pathways. β-2-Microglobulin (B2M) and vimentin (VIM) were upregulated in NPDR+DKD, enriched as hub proteins and strongly correlated with clinical features. ELISA showed that B2M (p<0.001) and VIM (p<0.0001) were significantly upregulated in NPDR+DKD compared with NPDR. In ROC analysis, B2M and VIM could distinguish DKD from NPDR with area under the curve values of 0.9000 (p < 0.0001) and 0.9950. Our proteomic study revealed alterations in the proteomic profile and identified VIM and B2M as early biomarkers of DKD, laying the foundation for the prevention, diagnosis and treatment of DKD.

Telomerase-initiated three-dimensional DNAzyme motor for monitoring of telomerase activity in living cells

Telomerase (TE) is recognized as a potential biomarker for early diagnosis, monitoring and treatment of cancer. At present, most of the methods for TE detection are only applicable to in vitro assays, and unsuitable for in vivo applications. Though a few intracellular probes have been reported to have good specificity for TE, they do not involve signal amplification, which hinders their applicability in scenarios requiring high sensitivity. It is rather challenging to develop highly sensitive biosensors for intracellular TE detection due to the difficulty in design TE probes with both high specificity and compatibility with signal amplification in living cells. Herein, a highly sensitive and selective three-dimensional DNAzyme motor for monitoring of TE activity in living cells was developed by innovatively integrating TE-mediated chain replacement reaction with a three-dimensional DNA walker. Specifically, the DNAzyme motor was constructed by assembling both DNAzyme substrates and swing arms made up of a hairpin-structured DNAzyme and a telomeric primer onto gold nanoparticles. TE in cells can activate the DNAzyme motor to carry out continuous chain replacement and substrate cutting reactions, and hence realize signal amplification in living cells. The DNAzyme motor was successfully utilized to monitor the dynamic changes of TE activity in four types of cells. Due to the advantages of simple synthesis, good biocompatibility and high sensitivity and specificity for TE, the proposed DNAzyme motor is expected to have great application potential in the early diagnosis of cancer.

Human placenta-based genome-wide mRNA sequencing to identify TEK/IGF1/CSF1/ANGPT2 as crucial segments in the pathogenesis of pre-eclampsia.

Pre-eclampsia is a pregnancy-specific disease commonly occurring in late pregnancy and has always been threatening maternal and fetal lives, yet the etiology and pathogenesis of pre-eclampsia are still uncertain. To depict the overall changes of genes at the genome-wide level and identify potential biomarkers for early diagnosis of pre-eclampsia, we conducted this study by collecting placenta samples donated by six pregnancy women, among whom three healthy women were included as controls and three women were diagnosed with pre-eclampsia. The placental sample tissues were then subjected to high-throughput sequencing. Furthermore, we proceeded with bioinformatics analysis and formulated the hypothesis of pre-eclampsia development and verified the potential targets of pre-eclampsia by immunohistochemistry. Demographically, we found that the baseline characteristics of study subjects were highly homogeneous except for gestational weeks and blood pressure, where the blood pressure was higher and gestational weeks were shorter in the pre-eclampsia group (systolic blood pressure 123.33 ± 4.62 vs. 148.67 ± 3.79 mmHg, p = 0.046; diastolic blood pressure 79.00 ± 5.20 vs. 88.33 ± 2.89 mmHg, p = 0.068; gestational weeks 39.33 ± 1.03 vs. 35.76 ± 2.41, p = 0.050). Specific pathological changes were identified, shown as syncytial knots, fibrinoid necrosis, perivillous fibrin deposition, and vasculitis. For high-throughput sequencing, a total of 1,891 dysregulated genes were determined, of which 960 genes were downregulated and 931 genes were upregulated. The bioinformatics analysis indicated that these genes, with different molecular functions in different parts of cells, were primarily responsible for endothelium development and vascular process in the circulatory system, and more than 10 signaling pathways were involved. By focusing on the PI3K-Akt signaling pathway, Rap1 signaling pathway, and disease enrichment analysis item pre-eclampsia, TEK, CSF1, IGF1, and ANGPT2 were identified to promote the development of pre-eclampsia. After confirming the placental expression of these genes at the protein level, we proposed the pathogenesis of pre-eclampsia as follows: the downregulation of TEK, CSF1, IGF1, and ANGPT2 may inhibit trophoblast proliferation and affect the remodeling of spiral arteries, causing maternal and fetal malperfusion and impeding nutrient exchange, thereby leading to clinical manifestations of pre-eclampsia.

Nanozyme-based cascade SPR signal amplification for immunosensing of nitrated alpha-synuclein.

A self-assembled nanozyme of iron porphyrin mediated supramolecular modified gold nanoparticles (FpA) was fabricated to determine nitrated alpha-synuclein as the Tyr 39 residue (nT39 α-Syn) of a potential biomarker for early diagnosis of Parkinson's disease (PD). Mechanically, localized surface plasmon resonance (LSPR) and the mass effect caused by catalytic deposition of the nanozyme contributed to a cascade signal amplification strategy. The sensor allowed a signal amplification and selective nT39 α-Syn bioanalysis with a 1.34-fold enhancement by cascade amplified SPR signal and double specific recognition. The detection limit was 1.78ng/mL in the detection range of 7-240ng/mL. Benefiting from the excellent immunosensor, this method can distinguish healthy people and PD patients usingactual samples. Overall, this strategy provides a nanozyme-based biosensing platform for the early diagnosis of PD and can be applied to detect other protein biomarkers, such as PD-L1.

Nocturnal urine 6-hydroxy sulfate melatonin is associated with the outcome of subjects with sepsis

Abstract Background It is imperative to identify potential biomarkers for early diagnosis and intervention of severe sepsis. This study investigated the relationship between melatonin secretion and outcome of sepsis after 28-day admission. Methods Patients with sepsis were randomly divided into an eye mask group and a control group. Blood and urine samples were collected from day 0 to 4. Relevant clinical data and 28-day survival data were obtained. Serum melatonin and urine 6-hydroxy sulfate melatonin (6-SMT) levels were measured. Results The outcome of sepsis did not differ between the eye mask and control groups. Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were significantly higher and monocyte human leukocyte antigen-DR (mHLA-DR), serum melatonin, nocturnal urine 6-SMT, and 24-hour urine 6-SMT levels were significantly lower in the nonsurvivors than in the survivors. The outcome at day 28 after admission was significantly associated with APACHE II and SOFA scores and mHLA-DR, nocturnal urine 6-SMT, and 24-hour urine 6-SMT levels. The areas under the receiver operating characteristic curve were 0.785, 0.740, 0.774, and 0.858 for APACHE II score, SOFA score, mHLA-DR expression, and nocturnal urine 6-SMT amount, respectively. The optimal thresholds for mHLA-DR and nocturnal urine 6-SMT were 30.13% and 43.60%, respectively. Nocturnal urine 6-SMT level was significantly and positively correlated with mHLA-DR expression. Conclusion Nocturnal urine 6-SMT level may be a feasible biomarker to predict the outcome of patients with sepsis. The use of a night-time eye mask has no significant effect on the outcome of sepsis. Clinical trials This study was registered at clinicaltrials.gov (NCT02304224).

MiR-574, miR-499, miR-125b, miR-106a, and miR-9 potentially target TGFBR-1 and TGFBR-2 genes involving in inflammatory response pathway: Potential novel biomarkers for chronic lymphocytic leukemia

MicroARNAs (miRNAs) are linked to a variety of cancers, which resulted in molecular pathway dysregulation in chronic lymphocytic leukemia (CLL). Using five dysregulated miRNAs identified by literature mining and in silico analysis, we were able to demonstrate the critical role that the TGFBR1 and TGFB receptor signaling pathways play in the state of CLL. Assays using real-time PCR were run on 30 patients and 30 healthy controls. This study showed that patient samples have considerably higher levels of miR-574 and miR-499. Notably, the same groups had lower expression levels of miR-125b, miR-106a, and miR-9. Furthermore, we suggested that TGFBR1 and TGFBR2 expression levels were decreased in patients, and we suggested that these genes could be targets for our profile miRNAs. In the current study, we hypothesized that miR-574, miR-499, miR-125b, miR-106a, and miR-9 are likely five new potential biomarkers for early diagnosis. Our research also showed that these profile miRNAs have a role in the formation of CLL, possibly through controlling the TGFBR1 and TGFBR2 pathways. This suggests that these profile miRNAs could serve as biomarkers for the diagnosis and prognosis of CLL.

Ultrasensitive electrochemical biosensor for microRNA-377 detection based on MXene-Au nanocomposite and G-quadruplex nano-amplification strategy

MicroRNAs (miRNAs) are considered as potential biomarkers for early diagnosis and prognostic assessment of diabetic nephropathy. In this work, an electrochemical biosensor for ultrasensitive detection of miRNA-377 was constructed based on MXene-Au nanocomposites and G-quadruplex nano-amplification strategy. As a promising nanocarrier, taking advantage of leveraging synergistic effects between Au nanoparticles (AuNPs) and MXene nanosheet, MXene-Au nanocomposites exhibited excellent electronic conductivity and provided massive active sites for DNA capture probe immobilization by Au-S bonds. AuNPs modified with Guanine-rich sequence DNA detection probes were designed as signal amplification nano-labels. Specifically, by inducing the transition of Guanine-rich detection probes to G-quadruplex, the strong affinity interaction between methylene blue and G-quadruplex could not only reflect trace concentration information of miRNA-377, but also lead to the further enhancement of electrochemical signal (2.7-fold). As a result, this newly designed biosensor exhibited superior sensing performance with a wide linear range from 10 aM to 100 pM and the limit of detection was as low as 1.35 aM. Compared with biosensors based on other nanocomposites and reported miRNA-377 biosensors, the proposed sensing platform did not require any thermal cycling or reverse transcription process, meeting the miRNA sensing requirements of convenient, sensitive, specific and stable. Furthermore, the as-constructed biosensor also displayed good selectivity, which was applied to accurate detection of miRNA-377 in human serum samples with satisfactory sensitivity, suggesting the biosensor system has promising applications in biological researches and early clinical diagnosis for diabetic nephropathy.

Potential biomarkers for early diagnosis of nephrotic changes in type 2 diabetic patients

Introduction: Type 2 diabetes (T2D) is metabolic disease with chronically elevated glucose levels, characterized by two main abnormalities: impairment of insulin secretion and decrease in insulin sensitivity. (1) Undiagnosed or poorly controlled, leads to complications such are blindness, renal insufficiency, amputation of lower extremities, heart disease, or stroke. Approximately 150 million people worldwide are affected by type 2 diabetes, with expectancy to double in next 20 years. Two factors are participating on clinical picture of type 2 diabetes: environment and genetics. (2) Materials and Methods: This is a prospective study carried out in the Department of Biochemistry at Index Medical College, Hospital and Research center, among the people attending the OP/IP departments, based on random selection. Informed consent was taken from the patients. Institutional Ethical Clearance Certificate was obtained. Number of samples: 150 samples were collected from the study subjects, of which Group A: 50 Normo-albuminuria, Group B: 50 Microalbuminuria and Group C: 50 Microalbuminuria with type 2 diabetes.