Cancer Medicine
·
2025
·Vol. 14
·期 9
·e70872
·
IF 3.1
Haitao Xu,Dangui Chen,Jia Lu,Long Zhong,Lihong Wang,Jian Ge
Background Acute myeloid leukemia (AML) represents a highly aggressive hematological malignancy characterized by a poor prognosis and a pressing demand for innovative diagnostic and prognostic biomarkers. Recent studies have indicated that ADP-ribosylation factor 6 (ARF6) is overexpressed across various cancer types; however, its specific role and implications in AML have yet to be thoroughly investigated. Methods To elucidate the clinical relevance and functional mechanisms of ARF6 in AML, we conducted an integrated analysis utilizing RNA sequencing data from The Cancer Genome Atlas (TCGA) alongside clinical samples and AML cell lines. The diagnostic potential of ARF6 was assessed through receiver operating characteristic curve analysis, and logistic regression was employed to identify factors correlating with elevated ARF6 expression. Functional assays were performed to elucidate the effects of ARF6 modulation on apoptosis, cell cycle progression, and AML cell proliferation, while mechanistic investigations focused on the PI3K/AKT/mTOR signaling pathway, particularly in the context of pharmacological PI3K inhibition. Results Our findings revealed a significant upregulation of ARF6 in AML compared to normal controls, with diagnostic efficacy indicated by an AUC of 0.793. Logistic regression analysis identified older age (> 60 years) and a higher white blood cell count (> 20 × 10 9 /L) as significant predictors of high ARF6 expression. Moreover, elevated ARF6 levels were independently associated with shorter overall survival (HR = 1.634, p = 0.045). Notably, ARF6 knockdown induced apoptosis and G0/G1 cell cycle arrest, whereas its overexpression yielded contrary effects. In addition, ARF6 activated the PI3K/AKT/mTOR pathway, which was abrogated by pharmacological PI3K inhibition. Conclusion Collectively, our findings establish ARF6 as a valuable diagnostic and prognostic marker in AML, driving disease progression through the activation of the PI3K/AKT/mTOR pathway. These insights not only enhance our understanding of AML pathology but also underscore the potential of targeting ARF6 for therapeutic intervention in AML treatment paradigms. Future research should aim at evaluating the therapeutic implications of targeting ARF6 in combination with existing treatment modalities.
研究领域:
血液学
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2016
·
IF 3.847
Jean-Charles Gautier,Xiaobing Zhou,Yi Yang,Thierry Gury,Zhe Qu,Xavier Palazzi,Jean-François Léonard,Mohamed Slaoui,Yaligara Veeranagouda,Isabelle Guizon,Eric Boitier,Aziz Filali-Ansary,Bart H.J. van den Berg,Oliver Poetz,Thomas Joos,Tianyi Zhang,Jufeng Wang,Philippe Detilleux,Bo Li
Most studies to evaluate kidney safety biomarkers have been performed in rats. This study was conducted in Cynomolgus monkeys in order to evaluate the potential usefulness of novel biomarkers of nephrotoxicity in this species. Groups of 3 males were given daily intramuscular injections of gentamicin , a nephrotoxic agent known to produce lesions in proximal tubules, at dose-levels of 10, 25, or 50 mg/kg/day for 10 days. Blood and 16-h urine samples were collected on Days − 7, − 3, 2, 4, 7, and at the end of the dosing period. Several novel kidney safety biomarkers were evaluated, with single- and multiplex immunoassays and in immunoprecipitation-LC/MS assays, in parallel to histopathology and conventional clinical pathology parameters. Treatment with gentamicin induced a dose-dependent increase in kidney tubular cell degeneration/necrosis, ranging from minimal to mild severity at 10 mg/kg/day, moderate at 25 mg/kg/day, and to severe at 50 mg/kg/day. The results showed that the novel urinary biomarkers, microalbumin, α1-microglobulin, clusterin , and osteopontin , together with the more traditional clinical pathology parameters, urinary total protein and N-acetyl-β-D-glucosaminidase (NAG), were more sensitive than blood urea nitrogen (BUN) and serum creatinine (sCr) to detect kidney injury in the monkeys given 10 mg/kg/day gentamicin for 10 days, a dose leading to an exposure which is slightly higher than the desired therapeutic exposure in clinics. Therefore, these urinary biomarkers represent non-invasive biomarkers of proximal tubule injury in Cynomolgus monkeys which may be potentially useful in humans.
研究领域:
毒理学
·
药理学
·
临床研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROTOXICOLOGY
·
2024
·
IF 3.4
Xuedan Deng,Yonghua Guo,Xiaofei Jin,Huifang Si,Kai Dai,Meng Deng,Jing He,Changfu Hao,Wu Yao
Although overexposure to manganese (Mn) is known to cause neurotoxic damage, effective exposure markers for assessing Mn loading in Mn-exposed workers are lacking. Here, we construct a Mn-exposed rat model to perform correlation analysis between Mn-induced neurological damage and Mn levels in various biological samples. We combine this analysis with epidemiological investigation to assess whether Mn concentrations in red blood cells (MnRBCs) and urine (MnU) can be used as valid exposure markers. The results show that Mn exposure resulted in neurotoxic damage in rats and that MnRBCs correlated well with neurological damage, showing potential as a novel Mn exposure biomarker. These findings provide a basis for health monitoring of Mn-exposed workers and the development of more appropriate biological exposure limits.
研究领域:
毒理学
·
神经科学
·
职业健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Liang Shi,Liangliang Lin,Lijiang Zhang,Lili Wu,Junjie Chi,Keqing Shi,Xing Dong
Tumor markers (TMs) are crucial indicators of preneoplastic and neoplastic diseases, which provide the basis for the accurate diagnosis of malignant tumors. We present a diagnostic platform utilizing magnetic photonic microspheres (mPCMs) for simultaneous detection of various sorts of TMs, specifically for reliable breast cancer identification. The multiplex detection capability of mPCMs stems from the color encoding function of the photonic crystal structure formed by self-assembled silica nanoparticles, while their magnetic responsiveness is achieved through ferric oxide nanoparticle doping. The ordered nanostructure offers a large specific surface area for biological detection, and the magnetically controlled movement enhances the capture efficiency of target biomarkers. Specifically, CA 15–3, miRNA-21, and exosomes are used as target biomarkers, reflecting different aspects of breast cancer biology. Our multivariate detection platform effectively identifies proteins, nucleic acids, and exosomes through specific binding and base complementary pairing. Thus, mPCMs provide a novel approach for the combined analysis of diverse biomarkers.
研究领域:
生物医学工程
·
肿瘤学
·
纳米技术
·
生物传感器
·
分子诊断学
✓ 已验证
产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Wenxin Xia,Yushu Wang,Jiahui Yue,Xueyan Fu
Background Honey-fried Licorice (HFL) is a dosage form of Glycyrrhizae Radix et Rhizome processed with honey, which has been recorded to exhibit better efficacy in tonifying the spleen compared to the raw product. In contrast, different processing methods of Glycyrrhizae Radix et Rhizome exhibit different efficacies and applications, but their current quality control index components remain consistent. Purpose Based on the discovery and research strategy of traditional Chinese medicine decoction piece quality marker (Q-marker), this study aimed to conduct a multidimensional integration of constituents absorbed into the body and metabolomics based on the tonifying spleen and stomach effects of HFL to effectively identify the Q-marker of HFL. Methods In this study, a spleen deficiency rat model was established using the "exhausted swimming + poor diet" method to investigate the pharmacodynamics of tonifying the spleen and stomach by HFL. The constituents absorbed into blood was conducted using UPLC-Q-TOF/MS, correlation analysis between metabolomics and constituents absorbed into blood recognized the Q-Marker of HFL. Results The pharmacodynamic data demonstrated that HFL exhibited a significant regulatory effect on the disordered levels of PP, trypsin, chymase, PL, α-Glu, MTL, GAS, VIP, IL-2, IFN-γ, and IgA in the spleen deficiency model. Furthermore, HFL was found to improve the pathological changes in the spleen and intestine in the spleen deficiency model, highlighting its significant "tonifying spleen and stomach" effect. In the serum containing HFL, a total of 17 constituents were identified as being absorbed into the blood. Among these, 11 were prototypical components, while 6 were metabolites. Metabolomics data revealed that 9 differentially expressed metabolic markers were observed. Furthermore, the analysis of endogenous metabolic markers indicated that 10 components exhibited significant correlations with these biomarkers. Conclusion The effect of "tonifying spleen and stomach" of HFL is closely related to the regulation of the material and energy metabolism pathway. The Q-Marker of HFL is glycyrrhizic acid and 18 β -glycyrrhetinic acid as the main control standards and liquiritin, isoliquiritin, liquiritin, isoliquiritin, isolicorice flavonol, licorice chalcone C and Formononetin were used as auxiliary standards.
研究领域:
中药学
·
药理学
·
代谢组学
·
药学
✓ 已验证
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Huimin Zheng,Shijin Zhou,Fenghong Zhang,Junsong Wang,Jinming Kong,Xueji Zhang
Lipopolysaccharide (LPS), a critical biomarker for Gram-negative bacterial infections, holds essential application value in clinical diagnosis, precision therapeutics, and public health surveillance through its ultrasensitive detection. This study successfully developed a novel electrochemical aptasensing platform by ring-opening metathesis polymerization (ROMP) - mediated signal amplification. The biosensor fabrication involves: (i) LPS aptamer-mediated target recognition; (ii) the modification of LPS glycan chains with the ROMP initiator (4-vinylbenzeneboronic acid) through boronate affinity; (iii) AquaMet-catalyzed ROMP of norbornene dicarboxylic anhydride to generate polymer chains on the electrode surface; (iv) 2,2,6,6-tetramethylpiperidin-4-ylamine (TEMPO) reporter immobilization through aminolysis between polymer terminal anhydride groups and TEMPO-NH 2 under mild conditions. This architecture enables remarkable signal amplification through a cascade mechanism: each LPS molecule can be functionalized with many ROMP initiation sites, and subsequent ROMP generates polymer chains incorporating thousands of TEMPO reporter molecules. The biosensor demonstrated exceptional performance, achieving an ultra-low detection limit of 0.338 fg/mL with a wide linear dynamic range spanning six orders of magnitude (1.0 fg/mL to 1.0 ng/mL). The study confirmed the biosensor's operational simplicity, superior sensitivity, excellent selectivity, cost-effectiveness, and robust anti-interference capability in complex clinical matrices. The modular design not only facilitates low-abundance LPS detection but also establishes a universal platform for ultrasensitive analysis of other glycosylated biomarkers, highlighting broad application potential in early disease diagnosis and therapeutic monitoring.
研究领域:
生物传感器
·
分析化学
·
生物化学
·
纳米技术
·
临床诊断
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Wendi Wang,Qing Han,Tianwei Wang,Jian Liu,Qingbin Ni,Jingyi Sun,Ying Wang,Baoliang Sun
Ischemic stroke (IS) has a high mortality rate. Multiplexed detection of IS core biomarkers is of great significance to early diagnosis and personalized treatment of IS patients. Whether pericytes, a key component of the neurovascular unit and blood-brain barrier located on the capillary wall, could serve as a promising biomarker for IS is to be explored. Herein, we observed a significant upregulation of inflammatory and apoptotic factors, such as MMP9, in pericytes subjected to in vitro ischemia. By transfecting pericytes with ASK1-shRNA to inhibit ASK1 expression, we noted reduced levels of inflammatory and apoptotic markers, including MMP9, as well as enhanced pericyte contraction and migration, thereby preserving the integrity of the blood-brain barrier. Additionally, ELISA assays conducted using plasma samples from patients with varying NIHSS scores revealed statistically significant concentrations of PDGFRβ and MMP9. Furthermore, we developed a highly sensitive and specific quantitative detection method for PDGFRβ and MMP9 based on fluorescence sensor technology. This novel detector exhibits high sensitivity, repeatability, and stability, enabling precise dual detection. Thus, the results suggest the great potential of the detection of PDGFRβ and MMP9 for early diagnosis of IS and prognosis prediction of the disease.
研究领域:
神经科学
·
医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SOILS AND SEDIMENTS
·
2025
·
IF 3
Jin Meiqing,Sun Yuanchao,Chai Bing,Wang Minghu,Wu Yuping,Wu Weihong,Zhou Qingwei,Qiu Linlin,Du Jia,Fu Li
Purpose Decabromodiphenyl ethane (DBDPE) and lead (Pb), two prevalent contaminants in e-waste dismantling areas, pose significant threats to soil ecosystem health. However, the ecotoxicological effects of their co-exposure on soil invertebrates remain poorly characterized. Methods Avoidance behavior, survival rate, and growth-inhibition assays were performed to assess the combined toxic effects of DBDPE and Pb on earthworm ( Eisenia fetida ) in an artificial soil system over exposure periods of 7–21 d. Responses from multiple biochemical biomarkers, including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), glutathione S-transferase (GST), and acid phosphatase (ACP) were also measured, and the data were integrated by the biomarker response index (BRI). Interaction between Pb and DBDPE on BRI was further analyzed by calculation of effect addition index (EAI). Results Avoidance behavior emerged as the most sensitive endpoint and exhibited concentration-dependent escalation under co-exposure conditions. While individual exposure to DBDPE (0–0.75 mg/kg) induced negligible impacts on growth and mortality, its combination with Pb (1000 mg/kg) resulted in significant synergistic effects. Similarly, biochemical biomarkers—including SOD, CAT, MDA, GST, and ACP—showed markedly greater alterations in co-exposure groups compared to single DBDPE treatments. The BRI revealed only slight alterations in biological health across most treatments. The EAI values indicated that antagonistic effects dominated the interaction between DBDPE and Pb. Conclusion Our findings demonstrated significant variation in biomarker sensitivity to pollutant exposure. Notably, short-term sub-lethal co-exposures may elicit synergistic effects on avoidance, growth, and mortality, revealing a time-concentration toxicity dependency. These results provide novel insights into the interaction between heavy metals and organo-pollutants and highlight the ecological hazards posed by emerging brominated flame retardants (e.g., DBDPE) in heavy metal-contaminated soil systems.
研究领域:
环境科学
·
毒理学
✓ 已验证
产品关联
DOI
高影响因子
JOR Spine
·
2024
·Vol. 7
·期 4
·e70004
·
IF 3.4
Daqian Zhou,Tao Liu,Yongliang Mei,Jiale Lv,Kang Cheng,Weiye Cai,Silong Gao,Daru Guo,Xianping Xie,Zongchao Liu
Background Intervertebral disc degeneration (IVDD) is an age-related orthopedic degenerative disease characterized by recurrent episodes of lower back pain, the pathogenesis of which is not fully understood. This study aimed to identify key biomarkers of IVDD and its causes. Methods We acquired three gene expression profiles from the Gene Expression Omnibus (GEO) database, GSE56081, GSE124272, and GSE153761, and used limma fast differential analysis to identify differentially expressed genes (DEGs) between normal and IVDD samples after removing batch effects. We applied weighted gene co-expression network (WGCNA) to identify the key modular genes in GSE124272 and intersected these with DEGs. Next, A protein–protein interaction network (PPI) was constructed, and Cytoscape was used to identify the Top 10 hub genes. Functional enrichment analyses were performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Three key genes were validated using Western Blot (WB) and qRT-PCR. Additionally, we predicted miRNAs involved in hub gene co-regulation and analyzed miRNA microarray data from GSE116726 to identify four differentially expressed miRNAs. Results We identified 10 hub genes using bioinformatics analysis, gene function enrichment analysis revealed that they were primarily enriched in pathways, such as the TNF signaling pathway. We chose JUNB, SOCS3, and CEBPB as hub genes and used WB and qRT-PCR to confirm their expression. All three genes were overexpressed in the IVDD model group compared to the control group. Furthermore, we identified four miRNAs involved in the co-regulation of the hub genes using miRNet prediction: mir-191-5p, mir-20a-5p, mir-155-5p, and mir-124-3p. Using limma difference analysis, we discovered that mir-191-5p, mir-20a-5p, and mir-155-5p were all down-regulated and expressed in IVDD samples, but mir-124-3p showed no significant change. Conclusion JUNB, SOCS3, and CEBPB were identified as key genes in IVDD, regulated by specific miRNAs, providing potential biomarkers for early diagnosis and therapeutic targets.
研究领域:
分子生物学
·
生物信息学
·
骨科医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CLINICA CHIMICA ACTA
·
2021
·
IF 3.786
Qian Gong,Xiuming Zhang,Aifeng Liang,Sinian Huang,Guangang Tian,Mengjiao Yuan,Qing Ke,Yijun Cai,Bin Yan,Jin Wang,Jinjin Wang
Background and aims Colorectal cancer (CRC) is part of the most widespread malignant tumors. At present, colonoscopy is a routine procedure in the diagnosis of CRC, but it is traumatic. Carcinoembryonic antigen, CA199, and CA242 are common serum markers for the diagnosis of CRC; however, they do not demonstrate satisfactory specificity and sensitivity for the diagnosis of CRC. Hence, Now it is necessary to screen many valuable serum biomarkers for CRC, proteomics methods have been used to investigate PTMs such as glycosylation of proteins with prominent roles in the occurrence and development of tumors. Methods This study screens altering glycosylated proteins of CRC tissues using LC-MS/MS quantitative glycoproteomics, and then these candidate biomarkers for CRC are further validated by serum glycoproteomics. Results The results of glycoproteomics in CRC tissues show that the abundance of 160 and 79 glycerogelatin proteins was obviously upregulated and downregulated compared with their adjacent tissues( P < 0.05). Bioinformatics analysis suggests that these molecules are mainly involved in many biological processes, including skeletal system development, collagen fibril organization, and receptor-mediated endocytosis. Results of serum glycoproteomics show that the changing trends of 2 protein glycosylation were consistent with MS results of CRC tissues, including ICAM1and APMAP. Areas under the ROC curve (AUC) results confirm that ICAM1and APMAP as early immune diagnosis markers of CRC has excellent sensitivity and specificity. Conclusion The ICAM1 and APMAP may serve as a potential tumor marker for CRC.
研究领域:
肿瘤学
·
蛋白质组学
·
医学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2023
·Vol. 28
·期 7
·145
·
IF 3.1
Cheng Chen,Xiaoxiao Meng,Yong Zhu,Jiaxiang Zhang,Ruilan Wang
Background: Early identification of sepsis improves the survival rate; however, it is one of the most challenging tasks for physicians, especially since symptoms are easily confused with those of systemic inflammatory response syndrome (SIRS). Our aim was to explore biomarkers for early identification of sepsis that would aid in its differential diagnosis. Methods: Eight patients with SIRS, eight with sepsis, and eight healthy controls were included in this study. Metabolites were screened using gas chromatography-mass spectrometry (GC-MS). Metabolism profiles were analyzed using the untargeted database of GC-MS from Lumingbio (LUG) database, and metabolic pathways were enriched based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The S-plot was used to screen the potential biomarkers distinguishing between patients with SIRS, sepsis, and healthy controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate potential biomarkers between SIRS and sepsis patients. Correlation analysis was used to measure the degree of correlation between differential metabolites. Correlation analysis between 2-deoxy-d-erythro-pentofuranose-5-phosphate and clinical indicators was performed. Results: There were 51 metabolites that were distributed in the SIRS group, and they were enriched with 18 metabolic pathways compared with healthy controls. Moreover, 63 metabolites in the sepsis group were significantly distinguishable compared to the healthy controls, and were associated with 21 metabolic pathways. Methyl 3-o-acetyl-d-galactopyranoside and N-acetylputrescine were found to be candidate biomarkers for distinguishing between SIRS, sepsis, and healthy controls using the S-plot model. Only four differential metabolites, including 2-deoxy-d-erythro-pentofuranose-5-phosphate, terbutaline, allantoic acid, and homovanillic acid (HVA), were enriched in the dopaminergic synapse and tyrosine metabolism pathways when sepsis patients were compared with SIRS patients. The Area Under Curve (AUC) of 2-deoxy-d-erythro-pentofuranose-5-phosphate was 0.9297, indicating a strong diagnostic ability for sepsis. A significant negative correlation was identified between 2-deoxy-d-erythro-pentofuranose-5-phosphate and lactate (r = –0.8756, p = 0.0044). Conclusions: Methyl 3-o-acetyl-d-galactopyranoside and N-acetylputrescine may be used as candidate biomarkers to distinguish SIRS and sepsis patients from healthy controls using GC-MS. 2-deoxy-d-erythro-pentofuranose-5-phosphate may be the candidate biomarker to distinguish sepsis from SIRS. Our study explored candidate biomarkers for the early identification of sepsis, which is vital for improving its prognosis.
研究领域:
医学
·
代谢组学
·
临床诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL GENETICS
·
2020
·Vol. 58
·期 4
·551-565
·
IF 2.027
Xie Shaolin,Zhou Aiguo,Feng Yongyong,Zhang Yue,Li Junyi,Sun Zhuolin,Fan Lanfen,Zou Jixing
Cytochrome P4501A (CYP1A) has been used as a specific biomarker for monitoring water contamination such as PAHs, PCBs and dioxins. In the present study, the cyp1a gene of Gambusia affinis was cloned and sequenced and their expressions under PAHs exposure were characterized. The newly identified cyp1a encodes a protein with 521 amino acids that shared 96–80% identity with other Cyprinodontiformes fishes. RT-PCR analysis revealed that the basal mRNA level of cyp1a was highly expressed in liver and intestine. The expression level of cyp1a was significantly induced by exposure to 100 μg/L 3, 4-Benzopyrene (BaP) for 5 days in the muscle, testis, brain, liver and intestine of adult male fish. Except in the testis, the induced mRNA level of cyp1a ultimately decreased after prolonging the exposure time to 25 days. As for testis, the induced mRNA level of cyp1a was maintained at a high level during the entire exposure time under 100 μg/L BaP exposure. Furthermore, the expression of cyp1a increased with exposure time under a relatively low exposure concentrations 1 μg/L. Regarding the effects of other PAHs, D(a,h)A, BbF, and BaA showed a statistically significant effect of induction on mRNA level of cyp1a in the muscle, testis, brain, liver and intestine.
研究领域:
环境科学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）