JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2023
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IF 3.4
Shijie Cao,Leyao Li,Hongwei An,Guobin Mao,Junbiao Dai,Yingxin Ma
Sensitive and accurate detection of interleukin 6 (IL-6) is crucial for the early diagnosis of cerebral infarction to improve patient survival rates. However, the low-abundance of IL-6 in cerebral infarction presents a significant challenge in developing effective diagnosis method. Herein, we studied and analyzed the strong fluorescence property of 4-aminophenol phosphate (APP) and developed an enzyme-linked immunosorbent assay (ELISA) for IL-6 detection. The detection was based on the integration of optical signal change induced by alkaline phosphatase (ALP)-catalyzed APP hydrolysis and ALP-mediated ELISA. The generated colorimetric signal of 4-aminophenol, APP hydrolysis product, was used for ELISA of IL-6 with a detection limit of 0.1 ng/mL, and the visual detection of IL-6 was achieved. The changes in APP fluorescence have a good linear relationship with the logarithm of IL-6 concentration in the range of 0.005 ng/mL to 5.0 ng/mL, with a detection limit of 0.001 ng/mL, which was 100 times lower than that of conventional pNPP-based ELISA. Furthermore, the constructed ELISA effectively distinguished between samples from patients with cerebral infarction and volunteers with non-cerebral infarction, and the severity of symptoms was well distinguished based on IL-6 measurement. The dual-mode ELISA demonstrated high feasibility of low-abundance biomarker detection and displayed good potential for accurate in vitro diagnosis.
研究领域:
生物医学工程
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临床诊断
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生物化学
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分子生物学
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DOI
PubMed
高影响因子
FEBS Open Bio
·
2023
·
IF 2.6
Yu Zhu,Longmei Wang,Rui Liu,Xiurong Ding,Song Yin,Yuankun Chen,Chuanlong Zhu,Zheng Wang,Wenting Li
Sepsis-induced acute kidney injury (SI-AKI) causes renal dysfunction and has a high mortality rate. Protein arginine methyltransferase-1 (PRMT1) is a key regulator of renal insufficiency. In this study, we explored the potential involvement of PRMT1 in SI-AKI. A murine model of SI-AKI was induced by cecal ligation and perforation (CLP). The expression and localization of PRMT1 and molecules involved in the TGF-β1/Smad3 and IL-6/STAT3 signaling pathways were detected in mouse kidney tissues by western blot, immunofluorescence, and immunohistochemistry. The association of PRMT1 with downstream molecules of the TGF-β1/Smad3 and IL-6/STAT3 signaling pathways were further verified in vitro in mouse renal tubular epithelial cells (mRTECs). CLP caused epithelial-mesenchymal transition (EMT), apoptosis, and inflammation in renal tissues, and this was alleviated by inhibition of PRMT1. Inhibition of PRMT1 in SI-AKI mice decreased the expression of TGF-β1 and phosphorylation of Smad3 in the renal cortex, and downregulated the expression of sIL-6R and phosphorylation of STAT3 in the medulla. Knockdown of PRMT1 in mRTECs restricted the expression of Cox-2, E-cad, Pro-caspase3 and p-Smad3 (involved in the TGF-β1-mediated signaling pathway), and blocked IL-6/sIL-6R, inducing the expression of Cox-2 and p-STAT3. In conclusion, our findings suggest inhibition of PRMT1 mitigates SI-AKI by inactivating the TGF-β1/Smad3 pathway in the cortex and IL-6/STAT3 pathway in the medulla. Our findings may aid in the identification of potential therapeutic target molecules for SI-AKI.
研究领域:
肾病学
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免疫学
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分子生物学
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病理生理学
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DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
·
2024
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IF 4.6
Jiangxia Wang,Runlin Gui,Yang Li,Zhuozhuo Li,Zi Li,Shanshan Liu,Miao Zhang,Lu Qian,Xiaobin Fan,Yuyan Xiong
Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic ovulation dysfunction and overproduction of androgens. Women with PCOS are commonly accompanied by insulin resistance (IR), which can impair insulin sensitivity and elevate blood glucose levels. IR promotes ovarian cysts, ovulatory dysfunction, and menstrual irregularities in women patients, leading to the pathogenesis of PCOS. Secreted frizzled-related protein 4 (SFRP4), a secreted glycoprotein, exhibits significantly elevated expression levels in obese individuals with IR and PCOS. Whereas, whether it plays a role in regulating IR-induced PCOS still has yet to be understood. In this study, we respectively established in vitro IR-induced hyperandrogenism in human ovarian granular cells and in vivo IR-induced PCOS models in mice to investigate the action mechanisms of SFRP4 in modulating IR-induced PCOS. Here, we revealed that SFRP4 expression levels in both mRNA and protein were remarkably upregulated in the IR-induced hyperandrogenism with elevated testosterone in the human ovarian granulosa cell line KGN. Under normal conditions without hyperandrogenism, overexpressing SFRP4 triggered the remarkable elevation of testosterone along with the increased nuclear translocation of β-catenin, cell apoptosis and proinflammatory cytokine IL-6. Furthermore, we found that phytopharmaceutical disruption of SFRP4 by genistein ameliorated IR-induced increase in testosterone in ovarian granular cells, and IR-induced PCOS in high-fat diet obese mice. Our study reveals that SFRP4 contributes to IR-induced PCOS by triggering ovarian granulosa cell hyperandrogenism and apoptosis through the nuclear β-catenin/IL-6 signaling axis. Elucidating the role of SFRP4 in PCOS may provide a novel therapeutic strategy for IR-related PCOS therapy.
研究领域:
内分泌学
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生殖医学
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分子生物学
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DOI
PubMed
高影响因子
Annals of Medicine and Surgery
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2023
·Vol. 85
·期 11
·5469
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IF 1.7
Ren Yuzhe,Li Xing,Zhang Yuanjie,Yan Zilong
Xiaoqinglong decoction (XQLD) is widely used clinically in the treatment of childhood cough variant asthma (CVA). However, its potential mechanism is still unknown. In the present study, the authors investigate the biological network and signalling pathway of XQLD in treatment of childhood CVA using network pharmacology-based analysis and experimental validation. By using the Bioinformatics Analysis Tool Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) database, the authors confirmed the correlation between XQLD and asthma, and the authors screened 1338 potential target genes of Mahuang and Guizhi, the most active herbs in XQLD. By overlapping “Childhood asthma-related genes” of DisGeNET database, the authors identified 58 intersecting genes of Childhood asthma and 1338 target genes of Mahuang and Guizhi. The intersecting genes were used to construct the protein-to-protein interaction and performed Gene Ontology (GO) functional and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Gene Ontology enrichment analysis demonstrated 359 Biological Process terms, 16 Cellular Component terms, and 26 Molecular Function terms. Meantime, 75 terms of Kyoto Encyclopedia of Genes and Genomes signalling pathway were involved in enrichment analysis. These candidates showed a significant correlation with inflammatory response and positive regulation of tyrosine phosphorylation of STAT protein. In addition, XQLD treatment significantly upregulated serum interferon-γ expression, and downregulated serum interlukin-6 expression of CVA mice. XQLD treatment significantly inhibited phosphorylation of STAT3 in bronchial-lung tissues. Our data suggest that XQLD effectively alleviated bronchial-lung tissue damage in CVA mice and inhibited the body inflammatory response by regulating interlukin-6/STAT3 signalling pathway.
研究领域:
药理学
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免疫学
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分子生物学
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中医
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DOI
PubMed
高影响因子
Scientific Reports
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2015
·Vol. 5
·期 1
·1-17
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IF 5.578
Cao Wei,Liu Ying,Zhang Ran,Zhang Bo,Wang Teng,Zhu Xianbing,Mei Lin,Chen Hongbo,Zhang Hongling,Ming Pinghong,Huang Laiqiang
Tyrosine kinase inhibitors (TKIs) are mostly used in non-small cell lung cancer (NSCLC) treatment. Unfortunately, treatment with Gefitinib for a period of time will result in drug resistance and cause treatment failure in clinic. Therefore, exploring novel compounds to overcome this resistance is urgently required. Here we investigated the antitumor effect of homoharringtonine (HHT), a natural compound extracted from Cephalotaxus harringtonia , on Gefitinib-resistant NSCLC cell lines in vitro and in viv o. NCI-H1975 cells with EGFR T790M mutation are more sensitive to HHT treatment compared with that of A549 cells with wild type EGFR. HHT inhibited cells growth, cell viability and colony formation, as well as induced cell apoptosis through mitochondria pathway. Furthermore, we explored the mechanism of HHT inhibition on NSCLC cells. Higher level of interleukin-6 (IL-6) existed in lung cancer patients and mutant EGFR and TGFβ signal requires the upregulation of IL-6 through the gp130/JAK pathway to overactive STAT3, an oncogenic protein which has been considered as a potential target for cancer therapy. HHT reversiblely inhibited IL-6-induced STAT3 Tyrosine 705 phosphorylation and reduced anti-apoptotic proteins expression. Gefitinib-resistant NSCLC xenograft tests also confirmed the antitumor effect of HHT in vivo . Consequently, HHT has the potential in Gefitinib-resistant NSCLC treatment.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2022
·Vol. 23
·期 18
·10887
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IF 6.208
Jing Jie,Guomu Liu,Jingyue Feng,Desheng Huo,Yixuan Wu,Hongyan Yuan,Guixiang Tai,Weihua Ni
Our previous study found that CpG oligodeoxynucleotides 1826 (CpG 1826), combined with mucin 1 (MUC1)-maltose-binding protein (MBP) (M-M), had certain antitumor activity. However, this combination is less than ideal for tumor suppression (tumors vary in size and vary widely among individuals), with a drawback being that CpG 1826 is unstable. To solve these problems, here, we evaluate MF59/CpG 1826 as a compound adjuvant with M-M vaccine on immune response, tumor suppression and survival. The results showed that MF59 could promote the CpG 1826/M-M vaccine-induced tumor growth inhibition and a Th1-prone cellular immune response, as well as reduce the individual differences of tumor growth and prolonged prophylactic and therapeutic mouse survival. Further research showed that MF59 promotes the maturation of DCs stimulated by CpG1826/M-M, resulting in Th1 polarization. The possible mechanism is speculated to be that MF59 could significantly prolong the retention time of CpG 1826, or the combination of CpG 1826 and M-M, as well as downregulate IL-6/STAT3 involved in MF59 combined CpG 1826-induced dendritic cell maturation. This study clarifies the utility of MF59/CpG 1826 as a vaccine compound adjuvant, laying the theoretical basis for the development of a novel M-M vaccine.Keywords:MF59;CpG 1826;compound adjuvant;tumor vaccine;MUC1-MBP;dendritic cells
研究领域:
免疫学
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肿瘤学
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疫苗学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2025
·
IF 4.5
Xiaoqiang Huang,Guohua Ru,Hengyun Tian,Pengbo Zhang,Hongchang Zhao,Shouren Zhang,Sijie Wang,An Jia,Wanli Zhao
Background Benign prostatic hyperplasia (BPH) significantly compromises patients' quality of life, has detrimental effects on both physical and mental well-being, and poses a substantial economic burden. Current pharmacological interventions primarily focus on symptom relief; nevertheless, their associated adverse effects are evident. Rape bee pollen and maca are both homologous food products, which are not only rich in nutrition, but also have many biological activities. There is no report on the combination of rape bee pollen and maca in benign prostatic hyperplasia therapy, and no report on the molecular mechanism. This study aims to systematically investigate the therapeutic efficacy and underlying molecular mechanisms of a chewable tablet formulation containing rape bee pollen and maca in the management of BPH. Methods First, the chewable tablets were prepared from rape bee pollen and maca, and the High Performance Liquid Chromatography (HPLC) fingerprint was established. During a 4-week period, rats were subjected to subcutaneous injections of testosterone propionate solution to establish a BPH model, while simultaneously receiving orally administered chewable tablets for BPH treatment via gavage. We assessed the body weight, prostate tissue index, serum levels of dihydrotestosterone (DHT), testosterone (T), estradiol (E2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) levels in rats. Prostate tissues were collected for histopathological analysis. The protein expression levels of IL-6, phosphorylated Janus kinase 2 ( p -JAK2), and phosphorylated signal transducer and activator of transcription 3 ( p -STAT3) were determined by Western blotting. Rat feces were collected aseptically for 16S rDNA gene sequencing to assess gut microbiota levels. Additionally, our research findings demonstrate that the combined application of rape pollen and maca exhibits superior therapeutic efficacy compared to the individual use of either rape pollen or maca alone. Results We prepared the rape bee pollen and maca chewable tablets, established the HPLC fingerprint map, and quantitatively analyzed four of these main components. We found that the rape bee pollen and maca chewable tablets significantly inhibited DHT, T, E2, E2/T ratio, IL-6, TNF-α, and IL-1β and reduced MDA levels and increased SOD, GSH levels. 16S rDNA gene sequencing revealed that the chewable tablet increased the abundance of the beneficial bacteria Faecalibacterium, Collinsella, Phascolarctobacterium, Kineothrix , and Lactobacillus , and decreased that of the pro-inflammatory bacterium Prevotella . Western blot indicated that the chewable tablet could significantly inhibit the IL-6, p -JAK2, and p -STAT3 protein expression levels. Conclusion We found that rape bee pollen and maca chewable tablets had a protective effect on rats with BPH, and also found that the combination of rape bee pollen and maca was better than separate application. The mechanism may be related to the gut microbiota and IL-6/JAK2/STAT3 signaling pathway.
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PubMed
高影响因子
Food & Function
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2023
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IF 6.1
Jiachen Zhuang,Qianqian Wang,Fei Shen,Jing Wang,Juan Du,Peng Yu,Fengqin Feng,Minjie Zhao
This study investigated the immunomodulatory effects of soft-shelled turtle (Pelodiscus sinensis) peptide (TP) and Chinese pond turtle (Chinemys reevesii) peptide (TMP) on the intestinal mucosal immune system (IMIS). The results demonstrated that TP and TMP improved holistic immunity by restoring the vital immune organ atrophy and proliferation capacity of spleen immune cells. Moreover, TP and TMP significantly increased the serum content of IgA and cytokines that are responsible for immune cell activation and antigen clearance. TP and TMP promoted intestinal B cell activation, class switching recombination, and antibody secreting processes in a T cell-independent manner to increase the SIgA content. Furthermore, TP and TMP enhanced the intestinal barrier by increasing the protein expression of tight junctions (TJs) and adhesion junctions (AJs) and ameliorating the intestinal morphology. Mechanistically, TP and TMP activated the AHR/IL-22/STAT3/IL-6 axis to enhance the IgA response and improve the intestinal barrier, indicating their potential in intestinal health modulation.
研究领域:
免疫学
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胃肠病学
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药理学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2021
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IF 7.46
Ting Zhou,Dechan Lu,Qiutian She,Cairou Chen,Jingbo Chen,Zufang Huang,Shangyuan Feng,Ruiyun You,Yudong Lu
We successfully prepared a two-dimensional surface enhanced Raman spectroscopy(SERS) substrate for the trace detection of Interleukin-6(IL-6) in plasma. Glycoproteins in serum were captured by a two-dimensional silver plate modified with 4-mercaptobenzoic acid (4-MPBA). And then, the [email protected] core-shell nanoprobes modified with IL-6 antibody accurately recognized IL-6 glycoprotein. The [email protected] NPs were embedded with Prussian Blue (PB) molecule, which only peaked at 2172 cm −1 in the biological silence zone. The calibration model of 4-MPBA and PB double signal molecules can avoid the interference of other glycoprotein macromolecules in the environment, thus realizing the quantitative detection of IL-6. The results showed that the higher the IL-6 content, the stronger the Raman signal. And the detection limit of IL-6 in serum can reach 5 pg/mL, the applicable range is 0.5–50000 pg/mL (R 2 = 0.9928). Therefore, this method can be used as a multifunctional SERS activity technology, which can be used to detect IL-6 ultra-sensitively and quantitatively.
研究领域:
生物传感
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分析化学
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分子诊断
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产品关联
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
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2023
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IF 5.7
Wang Cai,Xin Dongyuan,Yue Qianwen,Wan Huiyu,Li Qian,Wang Ying,Wu Jingguo
Introduction: Interleukin-6 (IL-6) is a multifunctional polypeptide cytokine composed of two glycoprotein chains, which plays an important role in many cellular reactions, pathological processes, diagnosis and treatment of diseases and so on. The detection of IL-6 plays a promising role in the cognition of clinical diseases.Methods: 4-mercaptobenzoic acid (4-MBA) was immobilized on the gold nanoparticles modified platinum carbon (PC) electrode with the linker IL-6 antibody, and finally formed an electrochemical sensor that specifically recognized IL-6. Through the highly specific antigen-antibody reaction, the IL-6 concentration of the samples to be detected. The performance of the sensor was studied by cyclic voltammetry (CV) and differential pulse voltammetry (DPV).Results: The experimental results showed that the linear detection range of the sensor for IL-6 was 100 pg/mL–700 pg/mL and the detection limit was 3 pg/mL. In addition, the sensor had the advantages of high specificity, high sensitivity, high stability and reproducibility under the interference environment of bovine serum albumin (BSA), glutathione (GSH), glycine (Gly) and neuron specific enolase (NSE), which provided a prospect for specific antigen detection sensor.Discussion: The prepared electrochemical sensor successfully detected the content of IL-6 in standard and biological samples, showing excellent detection performance. No significant difference was found between the detection results of the sensor and that of ELISA. The sensor showed a very broad prospect in the application and detection of clinical samples.
研究领域:
生物医学工程
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免疫学
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临床检验
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产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2015
·Vol. 86
·期 4
·753-763
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IF 2.485
Jianpeng Feng,Bing Xiao,Wenbo Chen,Ting Ding,Lingfeng Chen,Pengtian Yu,Fengli Xu,Huajie Zhang,Zhiguo Liu,Guang Liang
We previously reported a symmetric monocarbonyl analog of curcumin (MACs), C66, which demonstrated potential anti-inflammatory activity and low toxicity. In continuation of our ongoing research, we designed and synthesized 34 asymmetric MACs based on C66 as a lead molecule. A majority of the C66 analogs effectively inhibited LPS induction of TNF- α and IL-6 expression. Additionally, a preliminary SAR was conducted. Furthermore, active compounds 4a11 and 4a16 were found to effectively reduce the W/D ratio in the lungs and the protein concentration in the bronchoalveolar lavage fluid (BALF). Meanwhile, a histopathological examination indicated that these two analogs significantly attenuate tissue injury in the lungs with LPS-induced ALI rats. 4a11 and 4a16 also inhibited mRNA expression of several inflammatory cytokines, including TNF- α , IL-6, IL-1 β , COX-2, ICAM-1 and VCAM-1, in the Beas-2B cells after LPS challenge. Altogether, the data exhibit a series of new C66 analogs as promising anti-inflammatory agents for the treatment of LPS-induced ALI.
研究领域:
药理学
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合成化学
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免疫学
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DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2026
·
IF 3.1
Yanping Lu,Yaqi Li,Yuqi Tong,Lian Huang,Zhaohui Zhang
Beryllium is widely used in nuclear technology, aerospace, and defense. Long-term beryllium exposure causes chronic beryllium disease (CBD) characterized predominantly by pulmonary fibrosis. Cellular senescence is an important mechanism underlying pulmonary fibrosis, and the IL-6/STAT3 pathway has been implicated as a central axis linking inflammation, senescence, and tissue remodeling. However, whether this pathway promotes beryllium sulfate (BeSO 4 )–induced pulmonary fibrosis through regulation of senescence remains unclear. Herein, Sprague–Dawley rats were exposed to BeSO 4 , and hematoxylin–eosin (H&E) and Masson's trichrome staining were used to assess lung injury and fibrosis. Immunohistochemistry (IHC) assays were used to assess fibrosis-related factors, pathway molecules, and senescence markers in the lung tissues. In vitro, A549 cells were pretreated with the IL-6/STAT3 inhibitor LMT-28 before BeSO 4 exposure, and alterations in cell morphology, proliferation, senescence-related markers, and fibrosis-related markers were evaluated. The results demonstrated that BeSO 4 exposure promoted cellular senescence and pulmonary fibrogenesis via activating IL-6/STAT3 signaling, whereas LMT-28 treatment significantly attenuated these processes. These findings elucidate the molecular mechanism by which BeSO 4 induces pulmonary fibrosis through cellular aging, providing a basis for the discovery of potential therapeutic targets.
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DOI
PubMed
高影响因子
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