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Consumption of herbal products containing pyrrolizidine alkaloids (PAs) is one of the major causes for hepatic sinusoidal obstruction syndrome (HSOS), a deadly liver disease. However, the crucial metabolic variation and biomarkers which can reflect these changes remain amphibious and thus to result in a lack of effective prevention, diagnosis and treatments against this disease. The aim of the study was to determine the impact of HSOS caused by PA exposure, and to translate metabolomics-derived biomarkers to the mechanism. In present study, cholic acid species (namely, cholic acid, taurine conjugated-cholic acid, and glycine conjugated-cholic acid) were identified as the candidate biomarkers (area under the ROC curve 0.968 [95% CI 0.908–0.994], sensitivity 83.87%, specificity 96.55%) for PA-HSOS using two independent cohorts of patients with PA-HSOS. The increased primary bile acid biosynthesis and decreased liver expression of farnesoid X receptor (FXR, which is known to inhibit bile acid biosynthesis in hepatocytes) were highlighted in PA-HSOS patients. Furtherly, a murine PA-HSOS model induced by senecionine (50 mg/kg, p.o.), a hepatotoxic PA, showed increased biosynthesis of cholic acid species via inhibition of hepatic FXR-SHP singling and treatment with the FXR agonist obeticholic acid restored the cholic acid species to the normal levels and protected mice from senecionine-induced HSOS. This work elucidates that increased levels of cholic acid species can serve as diagnostic biomarkers in PA-HSOS and targeting FXR may represent a therapeutic strategy for treating PA-HSOS in clinics. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most significant neoplasms with high morbidity and mortality. Activation of the programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) signaling pathway results in tumor immune evasion by suppressing the activity of T cells. The correlation of soluble PD-L1 (sPD-L1) in serum/plasma with clinicopathological features, lymph node metastasis, diagnosis and prognosis is less clear. The aim of this study was to investigate the relationship between sPD-L1 and clinicopathological features, and diagnosis potentialof CRC. Three hundred patients with CRC were included in this study. sPD-L1 was measured by ELISA. Pretreatment levels of sPD-L1 were significantly elevated in CRC patient sera compared to healthy control (HC) (P<0.001). The median value of sPD-L1 in HC, CRC with non-lymph node metastasis, and CRC with lymph node metastasis were 246.78±50.2pg/mL, 284.12±52.7pg/mL, and 321.31±55.3pg/mL, respectively. ROC analysis of sPD-L1 allowed significant differentiation between HC group and CRC group (lymph node metastasis and non lymph node metastasis (AUC=0.861, 95% CI 0.830-0.887, p<0.001). sPD-L1 is a potential biomarker for the diagnosis of CRC. Multivariate analysis showed that lymph node metastasis and tumor differentiation were independent prognostic factors (all P< 0.01), and sPD-L1 was not correlated with the CRC prognosis (p>0.05). [ABSTRACT FROM AUTHOR]

Tic disorders (TDs) are a series of childhood neuropsychiatric disorders characterized by involuntary motor and/or vocal tics and commonly comorbid with several other psychopathological and/or behavioral disorders (e.g., attention deficit hyperactivity disorder and obsessive–compulsive disorder), which indeed aggravate clinical symptoms and complicate diagnosis and treatment. Micro-RNAs (miRNAs) derived from small extracellular vesicles (sEVs) have been recognized as novel circulating biomarkers of disease. To identify specific miRNAs derived from plasma sEVs for TDs' diagnosis and prognosis, we used official EV isolation and purification methods to characterize the plasma-derived EV miRNAs from children with different types of TDs. Nanoparticle tracking analysis, transmission electron microscopy, and immunoblot analysis of EV surface markers were applied to confirm the features and quality of sEVs. The RNA sequencing (RNA-seq) approach was adapted to identify novel circulating sEVs-derived miRNAs with altered expression levels in paired comparisons of TDs versus healthy controls (HCs), transient tic disorder (TTD) versus chronic motor or vocal tic disorder (CTD), and TTD versus Tourette Syndrome (TS). GO term and KEGG pathway were performed for functional analysis and the receiver operator curve analysis was followed to test the diagnosis efficacy of differentially expressed miRNAs (DEMs) derived from plasma sEVs among paired groups, namely, TDs versus HCs, TTD versus CTD, and TTD versus TS. As a result, 10 miRNAs (hsa-let-7a, hsa-let-7b, hsa-let-7c, hsa-let-7e, hsa-let-7f, hsa-miR-25-3p, hsa-miR-29a-3p, hsa-miR-30b-5p, hsa-miR-125b-5p, and hsa-miR-1469) have demonstrated a significantly different expression signature in the TDs group compared to HCs with excellent area under curve (AUC) values of 0.99, 0.973, 0.997, 1, 0.99, 0.997, 0.987, 0.993, 0.977, and 0.997, respectively, and the diagnostic efficacy of miRNAs was also estimated for discriminating TTD from CTD or TS. In our research, we finally obtained several potential sEVs-derived miRNA biomarkers to assess the diagnosis and prognosis of TDs. [ABSTRACT FROM AUTHOR]

Babesiosis caused by Babesia species imposes an increasing threat to public-health and so far, there is no effective vaccine to prevent Babesia infections. Babesia surface antigen may participate in the invasion of erythrocytes. In our previous study, a surface antigen of B. microti merozoites, named as BmSP44 was identified as a dominant reactive antigen by protein microarray screening. To evaluate its potential applications in diagnosis and prevention of Babesiosis, the open reading frame encoding BmSP44 was cloned and the recombinant protein was expressed. In consistent with the protein microarray result, recombinant BmSP44 (rBmSP44) can be recognized by sera from B. microti infected mice. Immunofluorescence assays (IFA) confirmed that BmSP44 is a secreted protein and localized principally in the cytoplasm of the parasites. The parasitemia and Babesia gene copies were lower in mice administered rBmSP44 antisera compared with normal controls. Active immunization with rBmSP44 also afforded protection against B. microti infection. The concentrations of hemoglobin in rBmSP44 immunization group were higher than those in the control group. Importantly, vaccination of mice with rBmSP44 resulted in a Th1/Th2 mixed immune response with significantly elevated IL-10 and IFN-γ levels during the early stage of infection. Taken together, our results indicated that rBmSP44 can induce a protective immune response against Babesia infection. Thus, BmSP44 can be used as both a diagnosis marker and a vaccine candidate.

Objective To identify the hub genes and signal pathways of glioblastoma multiforme(GBM) by microarray and bioinformatics analysis method, and to find out the potential markers for early diagnosis and targeted therapy of GBM. Methods The expression profiling data of GBM was obtained from the GEO database. R software was used to screen differentially expressed genes (DEGs), and DEGs was annotated using DAVID online tools for GO ontology and KEGG signaling pathway enrichment. Moreover, protein-protein interaction network(PPI) was constructed and from which the hub genes were selected. Finally, the TCGA database was used to validate the hub genes. Results Samples Pearson correlation analysis showed that the expression profiling was reliable. Totally 2142 DEGs including 968 up-regulated genes and 1174 down-regulated genes were screened. GO and KEGG enrichment showed that the DEGs mainly correlated with cell cycle, cell division and proliferation, synaptic transmission and other biological functions and pathways. Pathway network analysis indicated that MAPK signal pathway played a core regulatory role in the network. In addition, 9 hub genes most related to GBM were screened from PPI network, and further confirmed by TCGA database. Conclusion KEGG signaling pathways and hub genes may reveal the molecular mechanism of the development of GBM, and the hub genes may be used as the molecular marker for early diagnosis and therapeutic targets of GBM.

Background: The current study aims to evaluate the expression of miR-148 in peripheral blood of patients with ulcerative colitis (UC) and to explore its relationship with the progression of UC. Methods: RT-qPCR was used to detect the expression of miR-148 in the peripheral blood of UC patients and healthy controls. Serum C-reactive protein (CRP) was detected by ELISA and erythrocyte sedimentation rate (ESR) was measured by automatic erythrocyte sedimentation analyzer. Pearson's method was used to analyze the correlation of miR-148 with CRP and ESR. The diagnostic value of peripheral blood miR-148 was analyzed by receiver operating characteristic (ROC). Results: The relative expression of miR-148 in the peripheral blood of UC patients was higher than that of the control group. Further study showed that peripheral blood miR-148 level in the UC group was positively correlated with CRP and ESR. Moreover, ROC analysis demonstrated that the area under curve (AUC) of miR-148 in diagnosing UC was 0.837 (p = 0.008, 95% CI: 0.748 - 0.925). When the cutoff was 4.746, the sensitivity and specificity were 86.9% and 91.5%, respectively. More importantly, peripheral blood miR-148 combined with ESR and hs- CRP demonstrated better diagnostic efficiency in active UC patients. Conclusions: In summary, enhanced expression of miR-148 in peripheral blood of UC patients may be expected to be an index for evaluating the activity of UC disease. [ABSTRACT FROM AUTHOR]

Résumé Les miARNs sont des petits ARNs non codant assurant la régulation post-transcriptionnelle de l’expression génique. Leur expression est tissu-spécifique et certains miARNs ont une valeur diagnostique et/ou pronostique de classes tumorales. Les miARNs sont impliqués dans les processus tumoraux par deux mécanismes: amplification ou délétion de régions chromosomiques renfermant des clusters de gènes codant des miARNs (effet quantitatif) ou modification des effets des miARNs sur leur gènes cibles par mutation dans le site d’interaction avec les ARNms (effet qualitatif). Leur spécificité, la possibilité de les mesurer dans le sang circulant, en font des biomarqueurs qui doivent être aussi considérés maintenant comme des marqueurs de sensibilité thérapeutique. Une meilleure connaissance des différents mécanismes d’action de ces miARNs permettra aussi d’envisager de nouvelles approches thérapeutiques. Summary MiRNAs are small non-coding RNAs ensuring the post-transcriptional regulation of gene expression. Their expression is tissue-specific and some miRNAs have diagnostic and / or prognostic value for tumor classes. MiRNAs are involved in tumorigenesis by two mechanisms: amplification or deletion of chromosomal regions containing clusters of genes encoding miRNAs (quantitative effect) or modification of the effects of miRNAs on their target genes by mutation in the region of interaction with the mRNA (qualitative effect). Their specificity, the possibility for miRNA measurement in blood, must now lead to consider miRNAs as markers for therapeutic management. A better understanding of the different regulatory mechanisms involving miRNAs will also consider new therapeutic approaches. [ABSTRACT FROM AUTHOR]

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Colorectal cancer (CRC) is one of the most significant neoplasms with high morbidity and mortality. Activation of the programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) signaling pathway results in tumor immune evasion by suppressing the activity of T cells. The correlation of soluble PD-L1 (sPD-L1) in serum/plasma with clinicopathological features, lymph node metastasis, diagnosis and prognosis is less clear. The aim of this study was to investigate the relationship between sPD-L1 and clinicopathological features, and diagnosis potentialof CRC. Three hundred patients with CRC were included in this study. sPD-L1 was measured by ELISA. Pretreatment levels of sPD-L1 were significantly elevated in CRC patient sera compared to healthy control (HC) ( P <0.001). The median value of sPD-L1 in HC, CRC with non-lymph node metastasis, and CRC with lymph node metastasis were 246.78±50.2pg/mL, 284.12±52.7pg/mL, and 321.31±55.3pg/mL, respectively. ROC analysis of sPD-L1 allowed significant differentiation between HC group and CRC group (lymph node metastasis and non lymph node metastasis (AUC=0.861, 95% CI 0.830-0.887, p<0.001). sPD-L1 is a potential biomarker for the diagnosis of CRC. Multivariate analysis showed that lymph node metastasis and tumor differentiation were independent prognostic factors (all P < 0.01), and sPD-L1 was not correlated with the CRC prognosis ( p >0.05)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shao, Xu, Lin, Gao, Gao and Wang.)

Babesiosis caused by Babesia species imposes an increasing threat to public-health and so far, there is no effective vaccine to prevent Babesia infections. Babesia surface antigen may participate in the invasion of erythrocytes. In our previous study, a surface antigen of B. microti merozoites, named as Bm SP44 was identified as a dominant reactive antigen by protein microarray screening. To evaluate its potential applications in diagnosis and prevention of Babesiosis, the open reading frame encoding Bm SP44 was cloned and the recombinant protein was expressed. In consistent with the protein microarray result, recombinant Bm SP44 (r Bm SP44) can be recognized by sera from B. microti infected mice. Immunofluorescence assays (IFA) confirmed that Bm SP44 is a secreted protein and localized principally in the cytoplasm of the parasites. The parasitemia and Babesia gene copies were lower in mice administered r Bm SP44 antisera compared with normal controls. Active immunization with r Bm SP44 also afforded protection against B. microti infection. The concentrations of hemoglobin in r Bm SP44 immunization group were higher than those in the control group. Importantly, vaccination of mice with r Bm SP44 resulted in a Th1/Th2 mixed immune response with significantly elevated IL-10 and IFN-γ levels during the early stage of infection. Taken together, our results indicated that r Bm SP44 can induce a protective immune response against Babesia infection. Thus, Bm SP44 can be used as both a diagnosis marker and a vaccine candidate., (Copyright © 2020 Wang, Wang, Huang, Xu, Chen, Dai and Zhou.)

Background: To find potential biomarkers for predicting disease progression in gastric cancer (GC)., Methods: An extensive bioinformatics study of the Cancer Genome Atlas (TCGA) and Oncomine datasets was conducted to define potential mRNA biomarkers for GC. The mRNA expression profiles of 375 GC and 32 neighboring noncancerous adrenal tissues were analyzed. The Oncomine database was used to validate the hub genes. The correlation between candidate hub gene expression and survival of GC patients was analyzed using the Kaplan-Meier method., Results: Ten differentially expressed genes were identified as hub genes, and CXCL8 was the only gene validated as being up-regulated in GC tissues compared to control tissues using both the TCGA and Oncomine databases. Immunofluorescence staining showed that CXCL8 was expressed in GC tissues, and its higher expression predicted worse relapse-free survival in GC patients., Conclusions: CXCL8 is a potential biomarker for predicting disease progression in GC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2019.12.52). The authors have no conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)

Background: Colon cancer is one of the most common malignant tumors, and B cell Translocation Gene (BTG)1 is involved in the occurrence and development of colon cancer, however, the underlying molecular mechanism remains unclear., Objective: In this study, we investigated the expression of BTG1 protein in colon cancer, and its association with clinicopathology and prognosis., Methods: The tumor specimens from 59 patients with colon cancer who had undergone radical colectomy were selected as the observation group. Para-carcinoma tissues from the same patients were selected as the control group. The expressions of BTG1 mRNA and protein in the specimen of two groups were analyzed by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot. According to the immunohistochemical results, the patients were divided into BTG1-negative and BTG1-positive groups. The postoperative cumulative survival rate in the two groups was analyzed. The association of the expression of BTG1 protein with the clinicopathological features and postoperative survival was investigated., Results: Compared with the control group, the expression levels of BTG1 mRNA and BTG1 protein were significantly decreased in the observation group (P < 0.05). Immunohistochemical analysis revealed that there were 12 positive tumor samples and 47 negative samples. The expression of BTG1 was negatively associated with the degree of differentiation and lymphatic metastasis. The cumulative survival rate of BTG1-positive patients was significantly increased compared with that of BTG1- negative patients (P < 0.05). Stepwise Cox regression analysis showed that lymphatic metastasis, tumor size and BTG1 expression level were independent prognostic factors for overall survival in patients with colon cancer., Conclusion: BTG1 protein in colon cancer tissues were expressed at low levels, which was associated with the clinicopathological features, postoperative recurrence and survival of patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)