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Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis

《医学前沿（英文）》 2022年 第16卷 第2期   页码 216-226 doi: 10.1007/s11684-022-0920-7

摘要： Hepatocellular carcinoma (HCC), which makes up the majority of liver cancer, is induced by the infection of hepatitis B/C virus. Biomarkers are needed to facilitate the early detection of HCC, which is often diagnosed too late for effective therapy. The tRNA-derived small RNAs (tsRNAs) play vital roles in tumorigenesis and are stable in circulation. However, the diagnostic values and biological functions of circulating tsRNAs, especially for HCC, are still unknown. In this study, we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum. We identified tRF-Gln-TTG-006, which was remarkably upregulated in HCC serum (training cohort: 24 HCC patients vs. 24 healthy controls). In the validation stage, we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity (80.4%) and specificity (79.4%) even in the early stage (Stage I: sensitivity, 79.0%; specificity, 74.8%; 155 healthy controls vs. 153 HCC patients from two cohorts). Moreover, in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells, and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays. In summary, our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.

关键词： tsRNA     biomarker     hepatocarcinoma    

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MiRNA-451 is a potential biomarker for estrogenicity in mouse uterus

Lingyan HOU, Yun LU, Ying LI, Li LI

《环境科学与工程前沿（英文）》 2014年 第8卷 第1期   页码 99-105 doi: 10.1007/s11783-013-0490-7

摘要： The uterotrophic assay has been commonly used to test environmental estrogens in vivo, however, it is often not sensitive enough sometimes. An alternative way is to evaluate estrogenicity through biomarker genes. MicroRNA (miRNA) is a class of regulatory gene, which has been shown to be a good biomarker for many diseases and toxicological effects in recent years, and some evidences showed that estrogen induced response was partially mediated by miRNAs. In this study, two types of microarrays were used to test the 17β-estradiol (E2) induced miRNA expression profile at different time points in the immature mouse uterus. Statistical analysis showed the aldehyde slide based array had less variation than the amino slide based array, and 11 dysregulated miRNAs were screened out for significant fold change. Real-time PCR was performed to further confirm that 4 out of 7 selected miRNAs, namely miR-451, miR-155, miR-335-5p, and miR-365, are E2 regulated miRNAs in the uterus. The function of the predicted targets of these miRNAs is involved in cell grow control, which is consistent with the main E2 function in the uterus. MiR-451 had similar strong responses to E2 in the uterus of both immature and overiectomized mice, and could be a potential biomarker for estrogenicity in the uterus.

关键词： estrogen     microRNA (miRNA)     microarray     biomarker    

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Plasma transthyretin is a nutritional biomarker in human morbidities

《医学前沿（英文）》 2022年 第16卷 第4期   页码 540-550 doi: 10.1007/s11684-022-0940-3

摘要： Transthyretin (TTR) is a small liver-secreted plasma protein that shows close correlations with changes in lean body mass (LBM) during the entire human lifespan and agglomerates the bulk of nitrogen (N)-containing substrates, hence constituting the cornerstone of body building. Amino acids (AAs) dietary restriction causes inhibition of TTR production and impairs the accretion of LBM reserves. Inflammatory disorders result in cytokine-induced abrogation of TTR synthesis and urinary leakage of nitrogenous catabolites. Taken together, the data indicate that malnutrition and inflammation may similarly suppress the production of TTR through distinct and unrelated pathophysiological mechanisms while operating in concert to downsize LBM stores. The hepatic synthesis of TTR integrates both machineries, acting as a marker of reduced LBM resources still available for defense and repair processes. TTR operates as a universal surrogate analyte that allows for the grading of residual LBM capacity to reflect disease burden. Measurement of TTR is a simple, rapid, and inexpensive micro-method that may be reproduced on a daily basis, hence ideally suited for the follow-up of the most intricated clinical situations and as a reliable predictor of any morbidity outcome.

关键词： lean body mass     nutritional status     transthyretin     malnutrition     inflammation     amyloidosis    

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Biosensor-based assay of exosome biomarker for early diagnosis of cancer

《医学前沿（英文）》 2022年 第16卷 第2期   页码 157-175 doi: 10.1007/s11684-021-0884-z

摘要： Cancer imposes a severe threat to people’s health and lives, thus pressing a huge medical and economic burden on individuals and communities. Therefore, early diagnosis of cancer is indispensable in the timely prevention and effective treatment for patients. Exosome has recently become an attractive cancer biomarker in noninvasive early diagnosis because of the unique physiology and pathology functions, which reflects remarkable information regarding the cancer microenvironment, and plays an important role in the occurrence and evolution of cancer. Meanwhile, biosensors have gained great attention for the detection of exosomes due to their superior properties, such as convenient operation, real-time readout, high sensitivity, and remarkable specificity, suggesting promising biomedical applications in the early diagnosis of cancer. In this review, the latest advances of biosensors regarding the assay of exosomes were summarized, and the superiorities of exosomes as markers for the early diagnosis of cancer were evaluated. Moreover, the recent challenges and further opportunities of developing effective biosensors for the early diagnosis of cancer were discussed.

关键词： biosensor     exosome     cancer diagnosis    

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Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis

Changlin Cao, Jingxian Gu, Jingyao Zhang

《医学前沿（英文）》 2017年 第11卷 第2期   页码 169-177 doi: 10.1007/s11684-017-0505-z

摘要： Sensitive and useful biomarkers for the diagnosis and prognosis of infectious diseases have been widely developed. An example of these biomarkers is triggering receptor expressed on myeloid cell-1 (TREM-1), which is a cell surface receptor expressed on monocytes/macrophages and neutrophils. TREM-1 amplifies inflammation by activating the TREM-1/DAP12 pathway. This pathway is triggered by the interaction of TREM-1 with ligands or stimulation by bacterial lipopolysaccharide. Consequently, pro-inflammatory cytokines and chemokines are secreted. Soluble TREM-1 (sTREM-1) is a special form of TREM-1 that can be directly tested in human body fluids and well-known biomarker for infectious diseases. sTREM-1 level can be potentially used for the early diagnosis and prognosis prediction of some infectious diseases, including infectious pleural effusion, lung infections, sepsis, bacterial meningitis, viral infections (e.g., Crimean Congo hemorrhagic fever and dengue fever), fungal infections (e.g., infection), and burn-related infections. sTREM-1 is a more sensitive and specific biomarker than traditional indices, such as C-reactive protein and procalcitonin levels, for these infectious diseases. Therefore, sTREM-1 is a feasible biomarker for the targeted therapy and rapid and early diagnosis of infectious diseases.

关键词： soluble triggering receptor expressed on myeloid cells-1     infectious diseases     diagnosis and prognosis     biomarker    

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Increased expression of coronin-1a in amyotrophic lateral sclerosis: a potential diagnostic biomarker

《医学前沿（英文）》 2022年 第16卷 第5期   页码 723-735 doi: 10.1007/s11684-021-0905-y

摘要： Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. At present, no definite ALS biomarkers are available. In this study, exosomes from the plasma of patients with ALS and healthy controls were extracted, and differentially expressed exosomal proteins were compared. Among them, the expression of exosomal coronin-1a (CORO1A) was 5.3-fold higher than that in the controls. CORO1A increased with disease progression at a certain proportion in the plasma of patients with ALS and in the spinal cord of ALS mice. CORO1A was also overexpressed in NSC-34 motor neuron-like cells, and apoptosis, oxidative stress, and autophagic protein expression were evaluated. CORO1A overexpression resulted in increased apoptosis and oxidative stress, overactivated autophagy, and hindered the formation of autolysosomes. Moreover, CORO1A activated Ca2+-dependent phosphatase calcineurin, thereby blocking the fusion of autophagosomes and lysosomes. The inhibition of calcineurin activation by cyclosporin A reversed the damaged autolysosomes. In conclusion, the role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.

关键词： amyotrophic lateral sclerosis     coronin-1a     autophagy     pathogenesis    

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iTRAQ-based quantitative analysis of cancer-derived secretory proteome reveals TPM2 as a potential diagnostic biomarker

null

《医学前沿（英文）》 2016年 第10卷 第3期   页码 278-285 doi: 10.1007/s11684-016-0453-z

摘要：

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. We aimed to find novel molecules as potential biomarkers for the early diagnosis of CRC. A serum-free conditioned medium was successfully collected from three pairs of CRC tissue and adjacent normal tissue. iTRAQ-based quantitative proteomic analysis was applied to compare the differences in secretome between primary CRC mucosa and adjacent normal mucosa. A total of 145 kinds of proteins were identified. Of these proteins, 29 were significantly different between CRC and normal tissue. Tropomyosin 2 β (TPM2) exhibited the most significant differences; as such, this protein was selected for further validation. Quantitative real-time PCR indicated that the mRNA expression of TPM2 significantly decreased in the CRC tissue compared with the paired adjacent normal tissue. Immunohistochemical analysis also confirmed that TPM2 was barely detected at protein levels in the CRC tissue. In summary, this study revealed potential molecules for future biomarker applications and provided an efficient approach for the differential analysis of cancer-associated secretome. TPM2 may be valuable for the early diagnosis of CRC.

关键词： iTRAQ     secretome     colorectal cancer     TPM2    

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Sepsis biomarkers: an omics perspective

null

《医学前沿（英文）》 2014年 第8卷 第1期   页码 58-67 doi: 10.1007/s11684-014-0318-2

摘要：

Sepsis is a common cause of death in hospitalized patients worldwide. The early detection of sepsis remains a great challenge for clinicians, and delayed diagnosis frequently undermines treatment efforts, thereby contributing to high mortality. Omics technologies allow high-throughput screening of sepsis biomarkers. This review describes currently available and novel sepsis biomarkers in the context of genomics, transcriptomics, proteomics, and metabolomics. The combination of these technologies can help refine the diagnosis of sepsis. This review paper serves as a reference for future studies that employ an integrated, multi-omics approach to disease identification.

关键词： sepsis     biomarker     genomics     transcriptomics     proteomics     metabolomics    

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U-shaped microRNA expression pattern could be a new concept biomarker for environmental estrogen

Rui Duan, Yun Lu, Lingyan Hou, Lina Du, Lequn Sun, Xingfan Tang

《环境科学与工程前沿（英文）》 2016年 第10卷 第6期 doi: 10.1007/s11783-016-0880-8

摘要： Estrogen regulates miRNA expression in a typical U-shaped dose-response pattern. E2 can regulate in the ventral prostate. Mouse ventral prostate is most sensitive to estrogen. Nonmonotonic dose-response in prostate could be a component of estrogen signature. Many studies have focused on environmental estrogen-related diseases. However, no consistent gene markers or signatures for estrogenicity have been discovered in mammals. This study investigated the estrogenic effects of 17β-estradiol on the prostate in immature male mice. Consistent U-shaped responses were seen in bodyweight, ventral prostate epithelial morphology, and miRNA expression levels. Specifically, most estradiol regulated miRNAs were downregulated at low doses of estradiol (0.2 and 2 mg·kg ), and whose expression returned to the control level at a larger dose (200 mg·kg ). The function of these regulated miRNAs is related to the prostate cancer and PI3K-Akt signaling pathways, which is consistent with the function of estradiol. Furthermore, the miRNA-processing machinery, Drosha, in the prostate was also regulated in a similar pattern, which could be a part of the U-shaped miRNA expression mechanism. All of these data indicate that the prostate is a reliable organ for evaluating estrogenic activity and that the typical nonmonotonic dose-response relationship could be used as a novel biomarker for estrogenicity.

关键词： miRNA     Prostate     Estradiol     Nonmonotonic dose-response     Estrogenicity     Drosha    

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study of Mycoplasma pneumoniae pneumonia reveals the Fc fragment of the IgG-binding protein as a serum biomarker

《医学前沿（英文）》 2022年 第16卷 第3期   页码 378-388 doi: 10.1007/s11684-021-0840-y

摘要： Macrolide and corticosteroid resistance has been reported in patients with Mycoplasma pneumoniae (MP) pneumonia (MPP). MP clearance is difficult to achieve through antibiotic treatment in sensitive patients with severe MPP (SMPP). SMPP in children might progress to airway remodeling and even bronchiolitis/bronchitis obliterans. Therefore, identifying serum biomarkers that indicate MPP progression and exploring new targeted drugs for SMPP treatment require urgency. In this study, serum samples were collected from patients with general MPP (GMPP) and SMPP to conduct proteomics profiling. The Fc fragment of the IgG-binding protein (FCGBP) was identified as the most promising indicator of SMPP. Biological enrichment analysis indicated uncontrolled inflammation in SMPP. ELISA results proved that the FCGBP level in patients with SMPP was substantially higher than that in patients with GMPP. Furthermore, the FCGBP levels showed a decreasing trend in patients with GMPP but the opposite trend in patients with SMPP during disease progression. Connectivity map analyses identified 25 possible targeted drugs for SMPP treatment. Among them, a mechanistic target of rapamycin kinase (mTOR) inhibitor, which is a macrolide compound and a cell proliferation inhibitor, was the most promising candidate for targeting SMPP. To our knowledge, this study was the first proteomics-based characterization of patients with SMPP and GMPP.

关键词： severe Mycoplasma pneumoniae pneumonia     children     proteomics     Fc fragment of the IgG-binding protein     mechanistic target of rapamycin kinase inhibitor    

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Current advances in the elimination of hepatitis B in China by 2030

null

《医学前沿（英文）》 2017年 第11卷 第4期   页码 490-501 doi: 10.1007/s11684-017-0598-4

摘要：

With its 78 million chronic carriers, hepatitis B virus (HBV) infection is still one of the leading public health challenges in China. Over the last two decades, China has made great progress on the prevention of HBV transmission through national vaccination programs. Zero transmission from mother to infant has been proposed as the current goal. Available anti-HBV therapy is efficacious in suppressing HBV replication; however, it fails to completely cure patients with chronic hepatitis B and even requires lifelong treatment. To reduce the costs and improve the efficacy, several trials have been recently conducted in China to optimize the current anti-HBV managements. Novel biomarkers were identified to predict treatment outcomes, and new promising treatment strategies were developed. Reports also indicate that coinfections of HBV with other hepatotropic viruses and human immunodeficiency virus are common in China and cause severe liver diseases, which should be recognized early and treated properly. Work is still needed to eliminate hepatitis B in China by 2030.

关键词： HBV     CHB     biomarker     functional cure     coinfection    

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Gut microbiota-dependent phenylacetylglutamine in cardiovascular disease: current knowledge and new insights

《医学前沿（英文）》 2024年 第18卷 第1期   页码 31-45 doi: 10.1007/s11684-024-1055-9

摘要： Phenylacetylglutamine (PAGln) is an amino acid derivate that comes from the amino acid phenylalanine. There are increasing studies showing that the level of PAGln is associated with the risk of different cardiovascular diseases. In this review, we discussed the metabolic pathway of PAGln production and the quantitative measurement methods of PAGln. We summarized the epidemiological evidence to show the role of PAGln in diagnostic and prognostic value in several cardiovascular diseases, such as heart failure, coronary heart disease/atherosclerosis, and cardiac arrhythmia. The underlying mechanism of PAGln is now considered to be related to the thrombotic potential of platelets via adrenergic receptors. Besides, other possible mechanisms such as inflammatory response and oxidative stress could also be induced by PAGln. Moreover, since PAGln is produced across different organs including the intestine, liver, and kidney, the cross-talk among multiple organs focused on the function of this uremic toxic metabolite. Finally, the prognostic value of PAGln compared to the classical biomarker was discussed and we also highlighted important gaps in knowledge and areas requiring future investigation of PAGln in cardiovascular diseases.

关键词： PAGln     cardiovascular disease     gut microbiota     uremic metabolite     biomarker    

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Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications

null

《医学前沿（英文）》 2015年 第9卷 第3期   页码 261-274 doi: 10.1007/s11684-015-0406-y

摘要：

Environmental pollution is one of the main causes of human cancer. Exposures to environmental carcinogens result in genetic and epigenetic alterations which induce cell transformation. Epigenetic changes caused by environmental pollution play important roles in the development and progression of environmental pollution-related cancers. Studies on DNA methylation are among the earliest and most conducted epigenetic research linked to cancer. In this review, the roles of DNA methylation in carcinogenesis and their significance in clinical medicine were summarized, and the effects of environmental pollutants, particularly air pollutants, on DNA methylation were introduced. Furthermore, prospective applications of DNA methylation to environmental pollution detection and cancer prevention were discussed.

关键词： environmental pollution     DNA methylation     cancer     biomarker     diagnosis     therapy     prevention    

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Progress on molecular biomarkers and classification of malignant gliomas

null

《医学前沿（英文）》 2013年 第7卷 第2期   页码 150-156 doi: 10.1007/s11684-013-0267-1

摘要：

Gliomas are the most common primary intracranial tumors in adults. Anaplastic gliomas (WHO grade III) and glioblastomas (WHO grade IV) represent the major groups of malignant gliomas in the brain. Several diagnostic, predictive, and prognostic biomarkers for malignant gliomas have been reported over the last few decades, and these markers have made great contributions to the accuracy of diagnosis, therapeutic decision making, and prognosis of patients. However, heterogeneity in patient outcomes may still be observed, which highlights the insufficiency of a classification system based purely on histopathology. Great efforts have been made to incorporate new information about the molecular landscape of gliomas into novel classifications that may potentially guide treatment. In this review, we summarize three distinctive biomarkers, three most commonly altered pathways, and three classifications based on microarray data in malignant gliomas.

关键词： malignant glioma     molecular biomarker     IDH1     MGMT     molecular classification    

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Predictive values of plasma TNFα and IL-8 for intracranial hemorrhage in patients with acute promyelocytic leukemia

《医学前沿（英文）》 2022年 第16卷 第6期   页码 909-918 doi: 10.1007/s11684-021-0890-1

摘要： In patients with acute promyelocytic leukemia (APL), intracranial hemorrhage (ICH), if not identified promptly, could be fatal. It is the leading cause of failure of induction and early death. Thus, biomarkers that could promptly predict severe complications are critical. Here, cytokine differences between patients with APL with and without ICH were investigated to develop predictive models for this complication. The initial cytokine profiling using plasma samples from 39 patients and 18 healthy donors found a series of cytokines that were remarkedly different between patients with APL and healthy controls. The APL patients were subsequently divided into high and low white blood cell count groups. Results showed that tumor necrosis factor α and interleukin 8 (IL-8) were vital in distinguishing patients with APL who did or did not develop ICH. In addition, verification in 81 patients with APL demonstrated that the two cytokines were positively correlated with the cumulative incidence of ICH. Finally, in-vitro and in-vivo experimental evidence were provided to show that IL-8 influenced the migration of APL-derived NB4 cells and impaired the blood–brain barrier in PML/RARα positive blast-transplanted FVB/NJ mice. These assessments may facilitate the early warning of ICH and reduce future mortality levels in APL.

关键词： acute promyelocytic leukemia     intracranial hemorrhage     cytokines     biomarker    

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标题 作者 时间 类型 操作

Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis

期刊论文

MiRNA-451 is a potential biomarker for estrogenicity in mouse uterus

Lingyan HOU, Yun LU, Ying LI, Li LI

期刊论文

Plasma transthyretin is a nutritional biomarker in human morbidities

期刊论文

Biosensor-based assay of exosome biomarker for early diagnosis of cancer

期刊论文

Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis

Changlin Cao, Jingxian Gu, Jingyao Zhang

期刊论文

Increased expression of coronin-1a in amyotrophic lateral sclerosis: a potential diagnostic biomarker

期刊论文

iTRAQ-based quantitative analysis of cancer-derived secretory proteome reveals TPM2 as a potential diagnostic biomarker

null

期刊论文

Sepsis biomarkers: an omics perspective

null

期刊论文

U-shaped microRNA expression pattern could be a new concept biomarker for environmental estrogen

Rui Duan, Yun Lu, Lingyan Hou, Lina Du, Lequn Sun, Xingfan Tang

期刊论文

study of Mycoplasma pneumoniae pneumonia reveals the Fc fragment of the IgG-binding protein as a serum biomarker

期刊论文

Current advances in the elimination of hepatitis B in China by 2030

null

期刊论文

Gut microbiota-dependent phenylacetylglutamine in cardiovascular disease: current knowledge and new insights

期刊论文

Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications

null

期刊论文

Progress on molecular biomarkers and classification of malignant gliomas

null

期刊论文

Predictive values of plasma TNFα and IL-8 for intracranial hemorrhage in patients with acute promyelocytic leukemia

期刊论文