ANALYTICAL CHEMISTRY
·
2016
·
IF 5.886
Wei Li,Wei Jiang,Shuang Dai,Lei Wang
Cytokines play important roles in the immune system and have been regarded as biomarkers. While single cytokine is not specific and accurate enough to meet the strict diagnosis in practice, in this work, we constructed a multiplexed detection method for cytokines based on dual bar-code strategy and single-molecule counting. Taking interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) as model analytes, first, the magnetic nanobead was functionalized with the second antibody and primary bar-code strands, forming a magnetic nanoprobe. Then, through the specific reaction of the second antibody and the antigen that fixed by the primary antibody, sandwich-type immunocomplex was formed on the substrate. Next, the primary bar-code strands as amplification units triggered multibranched hybridization chain reaction (mHCR), producing nicked double-stranded polymers with multiple branched arms, which were served as secondary bar-code strands. Finally, the secondary bar-code strands hybridized with the multimolecule labeled fluorescence probes, generating enhanced fluorescence signals. The numbers of fluorescence dots were counted one by one for quantification with epi-fluorescence microscope. By integrating the primary and secondary bar-code-based amplification strategy and the multimolecule labeled fluorescence probes, this method displayed an excellent sensitivity with the detection limits were both 5 fM. Unlike the typical bar-code assay that the bar-code strands should be released and identified on a microarray, this method is more direct. Moreover, because of the selective immune reaction and the dual bar-code mechanism, the resulting method could detect the two targets simultaneously. Multiple analysis in human serum was also performed, suggesting that our strategy was reliable and had a great potential application in early clinical diagnosis.
研究领域:
生物化学
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免疫学
·
分子生物学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2018
·
IF 3.929
Juan Wang,Wei Li,Jingfang Qin,Li Wang,Shenqi Wei,Huang Tang
A series of 6-substituted azaanthraquinone derivatives have been designed, synthesized, and their anti-inflammatory activities, antiaggregation effects on β-amyloid proteins, anticholinesterase and neuroprotective activity were tested. The new derivatives strongly suppressed NO and iNOS production and modulate the production of cytokines by decreasing TNF-a, IL-1β and IL-6 formation in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Meanwhile, the derivatives exhibited a significant in vitro inhibitory activity toward the self-induced Aβ aggregation. While, treatment of SH-SY5Y cells overexpressing the Swedish mutant form of human b-amyloid precursor protein (APPsw) with derivatives was associated with significant reduction of Aβ42 secretion levels. Moreover, the derivatives exhibited moderate inhibitory potency toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Further investigations indicated that compound 7b could attenuate H 2 O 2 -induced neurotoxicity toward SH-SY5Y neuroblastoma cells and half of the synthetic compounds were predicted to be able to cross the blood–brain barrier (BBB) to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay for BBB. Taken together, azaanthraquinone derivatives targeting multiple pathogenetic factors deserves further investigation for prevention and treatment of AD.
研究领域:
药理学
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神经科学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2019
·
IF 2.367
Jun Shi,Yanting Wu,Siyi Guo,Huidi Zhang,Guitian Chen,Xiaoqi Xu
The aim of this study was to investigate the efficacy of anti-VEGF antibody-modified Paeonol liposome gels (PAE-BEV-lip gels) in the prevention and treatment of hypertrophic scars (HS). Systematic optimization of the encapsulation process of anti-VEGF antibody-modified Paeonol liposomes (PAE-BEV-lips) was performed using Box–Behnken design with the optimized parameters as follows: SPC concentration of 7.36 mg mL−1; SPC-Chol-PAE:pNP-PEG3000-DOPE:BVE-PEG3000-DOPE ratio of 14:5:4:0.28:0.05, w/w; the hydration temperature of 41 °C; stripping using pH 7.5 sodium dihydrogen phosphate buffer; and ultrasound for 3 min (ultrasound time 2 s, interval 3 s, power 300 W). Using these conditions, the encapsulation efficiency of PAE reached the peak level, i.e. 73.61 ± 2.36%. The PAE-BEV-lips displayed unimodal size-distribution with a mean diameter of (235.7 ± 4.67) nm and a zeta potential of –(5.13 ± 0.25) mV. The investigation of the retention effect PAE-BEV-lip gels revealed a slower transdermal delivery rate, a remarkable dermal retention effect, and superior bioavailability compared to PAE gels and PAE conventional liposome gels (PAE-lip gels). Meanwhile, PAE-BEV-lip gels exhibited definite effects on the prevention and treatment of HS of the rabbit ears. The PAE-BEV-lip gels group showed a lower scar proliferation rate, fewer and looser collagenous fibers and fibromyocytes, more regular chondrocytes, less calcified tissue and fewer inflammatory cells compared to other groups. At the same time, PAE-BEV-lip gels significantly reduced scar hyperplasia index (1.34 ± 0.51) and levels of VEGF, TGF-β1 and TNF-α (30.90 ± 3.57, 733.2 ± 43.19 and 66.76 ± 2.98 ng·L−1, respectively), compared to the model group (p < .01).
研究领域:
药剂学
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皮肤病学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Yanping Wu,Ziyan Tang,Shumin Du,Jing Dai,Jintao Shen,Hong Niu,Xingshuang Song,Guiyu Huang,Lina Du,Yiguang Jin
High-altitude sleep disturbance is a common symptom of acute mountain sickness, which can be alleviated via modulation of the gut-brain axis. Quercetin (Que) is used to modulate gut microbiota and serves as a potential drug to regulate the gut-brain axis, but the poor solubility and bioavailability affect its biological functions. Here, Que nanoparticles (QNPs) were prepared with zein using an antisolvent method, and QNP-loaded calcium alginate hydrogel microspheres (QNP@HMs) were prepared using electrospinning technology to improve the gastrointestinal stability and intestinal adhesion of QNPs. In the mouse model of high-altitude sleep disturbance, oral administration of QNP@HMs before the mice entering high altitude prolonged sleep duration, improved blood cell recovery, spontaneous behavior and short-term memory, and reduced such inflammation factors as TNF- α and iNOS. Moreover, QNP@HMs enhanced the abundance of probiotics in the gut, including Lactobacillus and Lachnospira , and reduced intestinal inflammation. However, in the mice after gut sterilization by long-term oral antibiotics, QNP@HMs showed no therapeutic effect. QNP@HMs are a promising medication for the prevention of high-altitude sleep disturbance based on the gut-brain axis.
研究领域:
药理学
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生物技术
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神经科学
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微生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Jiqi Huang,Yifan Su,Qianyu Wang,Mingxiao Feng,Dawei Zhang,Qian Yu,Chunyan Yan
Ganoderma lucidum spores are tiny mature germ cells ejected from the abaxial side of the pileus and were responsible for multiple pharmacological properties. The defatted G. lucidum spores are the byproducts after the extraction of G. lucidum spores oil by supercritical fluid extraction technology, which have not been given sufficient attention. In order to fully utilize the resources of G. lucidum spores, a glucomannan (SGL90–1, 6.4 kDa) was isolated from the defatted G. lucidum spores. SGL90–1 was composed of mannose, glucose, galactose, and fucose in a molar ratio of 23.9:28.7:9.0:1.0. The backbone of SGL90–1 was consisted of →2,4)- α -D-Man p -(1→, →6)- β -D-Man p -(1→, →2,6)- α -D-Man p -(1→, →2)- α -D-Glc p -(1→, and →3,6)- β -D-Glc p -(1 → with seven side chains, and terminated with β -D-Man p -(1→, β -D-Glc p -(1→, α -L-Fuc p -(1→, and β -D-Gal f -(1→. Moreover, SGL90–1 could significantly elevate the phagocytic capability of RAW264.7 macrophages and promote the levels of nitric oxide (NO), tumor necrosis factor- α (TNF- α ), and interlrukin-6 (IL-6) through activating the TLR4/MyD88/NF-κB signaling pathway. Collectively, these findings demonstrated the potential of SGL90–1 as a natural functional food with strong immune-enhancing effect.
研究领域:
真菌学
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免疫学
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药理学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Nano Materials
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2024
·
IF 5.3
Ying Wang,Kunzhan Dong,Yan Zhang,Qi Li,Chang Liu,Shijie Cai,Zhiye Xu,Jingyang Shan,Sen Wang
Excessive inflammation can cause severe damage to biological tissues and organs, and current anti-inflammatory drugs still have certain limitations. This study aims to explore anti-inflammatory strategies. Nanozymes, a class of nanomaterials with enzyme-like catalytic properties, have gained significant attention in recent years. In this study, iron ion integrated coordination polymer nanodots (FNDs) were synthesized. The anti-inflammatory effects of FNDs were investigated from multiple aspects, including material characterization, antioxidant performance testing, in vitro cell experiments, and mouse model experiments. The results demonstrated that FNDs have the characteristics of small size, high stability, and excellent antioxidant capacity. In vitro cell experiments showed that FNDs significantly inhibited the production of LPS-induced TNF-α, IL-1β, and IL-6 in THP-1 macrophages. Further analysis of signaling pathways revealed that FNDs markedly suppressed the NF-κB and MAPK pathways and downregulated the expression of TLR4 and CD14 on the surface of macrophages. Experiments in mouse models indicated that FNDs significantly suppressed inflammation and cellular damage in organs such as the lungs and liver, and reduced the number of inflammatory cells and the concentrations of TNF-α, IL-1β, and IL-6 in peripheral blood. This study demonstrates that FNDs possess excellent antioxidant and anti-inflammatory properties, providing a strategy for the treatment of inflammatory diseases.
研究领域:
纳米技术
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免疫学
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药理学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
CHEMISTRY & BIODIVERSITY
·
2024
·
IF 2.3
Linhong He,Lijuan Zhang,Xi Bai
This study evaluated the effects of three extraction methods, hydrodistillation (HD), steam distillation (SD), and lipophilic solvent extraction (LSE), on the yield, chemical composition, and in vitro / in silico biological activities of Schizonepeta tenuifolia (Benth.) Briq essential oil (STEO). The highest yield of STEO was obtained by HD (0.750±0.040%), followed by SD (0.440±0.020%) and LSE (0.350±0.030%). Although their contents varied, menthone and pulegone predominated in HDEO, SDEO, and LSEO. HDEO displayed the strongest antioxidant ability, with a 2,2-diphenyl-1-picrylhydrazyl (DPPH) IC50 value of 14.164±0.090 mg/mL and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS) value of 0.326±0.023 mg/mL. SDEO demonstrated the highest antimicrobial activity against Staphylococcus aureus and Escherichia coli and HDEO the highest potent anti-inflammatory activity. The molecular docking of menthone and pulegone demonstrated strong binding to inflammatory targets, including prostaglandin-endoperoxide synthase 1 (PTGS1) and 2 (PTGS2) and tumor necrosis factor alpha (TNF-α). In short, the extraction method significantly affected the yield, composition, and biological activity of STEO.
研究领域:
药用植物学
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精油化学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL CHEMISTRY JOURNAL
·
2024
·Vol. 57
·期 12
·1872-1882
·
IF 0.8
Guo Haihua,Li Meng,Lin Yue,Zhai Zizhao,Wang Guanlin,Zhao Suqing
The diterpenoid isosteviol is one of the stevia derivatives that have reported various activities . In mice inhaling isosteviol, OVA- and ACh-induced bronchial asthma showed a dose-dependent improvement of a decline in the expression of inflammatory cytokines and the infiltration of basophils. Compared with inhalation of budesonide 0.6 mg/kg, sensitized mice inhaling 1.0 mg/kg dosage of isosteviol performed a higher tolerate against the ACh stimulation. In behavior tests, the 1.0 mg/kg isosteviol nebulization reached almost 80% of the level of budesonide with regard to the ameliorative effects on depression-like behavior and improvement in sport ability. In addition, lung and systemic inflammation were markedly prevented by isosteviol with a dosage of more than 0.6 mg/kg, which exhibited limited expression of IL-1β and TNF-α, less infiltration of basophils in lung tissues, and a low level of systemic immunocytes, which showed in hematoxylin and eosin staining, RT-PCR, and ELISA results. On the other hand, none of the abnormal pathology was found in both peripheral and central organs of all the administration groups. Generally, this study implicated that the mechanism could involve effects of isosteviol inhalation on the suppression of IL-1β and TNF-α to restrict a systemic upsurge of immunocytes and infiltration into the lung that prevents the occurrence of depression-like behavior and hypokinesia.
研究领域:
药理学
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免疫学
·
呼吸医学
✓ 已验证
产品关联
DOI
高影响因子
MEDICAL SCIENCE MONITOR
·
2020
·
IF 1.918
Feng Liu,Xuesong Zhang,Yong Ji
Background Intestinal epithelial barrier dysfunction is involved in the development and pathogenesis of intestinal diseases, such as irritable bowel syndrome, inflammatory bowel disease, and celiac disease. This study was performed to evaluate the ability of total flavonoid extract from hawthorn (TFH) to improve TNF-α-evoked intestinal epithelial barrier deficit. Material/Methods Caco-2 cells monolayers were exposed to TNF-α in different concentrations of TFH. Intestinal epithelial barrier function was evaluated using epithelial permeability and transepithelial electrical resistance (TER). Results Our findings showed that TFH alleviated the increase of paracellular permeability and the decline of transepithelial electrical resistance (TER) evoked by TNF-α. Additionally, 24-h pre-incubation with TFH inhibited TNF-α-evoked secretion of pro-inflammatory factors (IL-6, IL-8, MCP-1, and IL-1β). Furthermore, TFH inhibited TNF-α-evoked overexpression of pMLC and MLCK and alleviated breakdown of TJs protein (ZO-1 and occludin). The activations of Elk-1 and NFκBp65 were inhibited by TFH pre-incubation. Conclusions TFH can alleviate TNF-α-evoked intestinal epithelial barrier deficit via the NFκBp65-mediated MLCK-MLC signaling pathway.
研究领域:
药理学
·
免疫学
·
胃肠病学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
·
2023
·
IF 4.5
Linlin Zhang,Lei Cheng,Zhemeng Chen,Yi Fang,Changjiang Li,Min Chen,Peijie He,Haitao Wu,Jianzhang Wu,Jian Chen
Hypopharyngeal carcinoma is notorious for its poor prognosis among all head and neck cancers, posing a persistent challenge in clinical settings. The continuous hyperactivation of the NFκB signalling pathway has been noted in various cancer types, including hypopharyngeal carcinoma. In our quest to develop a novel drug that targets hypopharyngeal cancer via the NFκB pathway, we employed curcumin, a well-known lead compound, and performed chemical modifications to create a mono-carbonyl analogue called L42H17. This compound exhibited exceptional stability and displayed an enhanced binding affinity to myeloid differentiation protein 2 (MD2). Consistent with expectations, L42H17 demonstrated the ability to inhibit TNF-α-induced phosphorylation of inhibitor of κB (IκB) kinase (IKK), prevent IκB degradation, and subsequently impede NFκB-p65 nuclear translocation in hypopharyngeal cancer cells. Additionally, L42H17 exhibited a remarkable capacity to induce cell cycle arrest at the G2-M phase by inactivating the cdc2-cyclin B1 complex. Moreover, it facilitated cell apoptosis by reducing Bcl-2 levels and augmenting the expression of cle-PARP and cle-caspase3. Importantly, we observed a significant enhancement in the anti-cancer efficacy of L42H17 in a patient-derived tumour xenograft (PDTX) model of hypopharyngeal carcinoma. In conclusion, our findings strongly suggest that L42H17 holds promise as a potential candidate drug for the treatment of hypopharyngeal carcinoma in the future.
研究领域:
肿瘤学
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药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yuting Huang,Qianru Chen,Weijie Pan,Ying Zhang,Jiasheng Li,Xingyang Xue,Xinhe lei,Shumei Wang,Jiang Meng
Ethnopharmacological relevance As a traditional Chinese medicine , raw Moutan Cortex (RMC) has been used in clinical practice for thousands of years. However, its blood-cooling and blood-activating medicinal effects as well as the underlying mechanisms have not been preliminarily verified until recent years. Aim of the study Our group's previous network pharmacological studies suggested that RMC might exert its blood-activating and anti-inflammatory effects by modulating the coagulation-inflammation cascade pathway. Therefore, the present study aimed to further investigate the mechanisms relevant to the blood-activating and anti-inflammatory effects of RMC so as to provide more robust data supporting its clinical application. Materials and methods The inflammation and coagulation models of human umbilical vein endothelial cells (HUVECs) were induced by TNF-α; The rat models with blood-heat and blood-stasis syndrome (BHS) were constructed by ice-water bath with a combined use of epinephrine hydrochloride and dried yeast; The thrombus models of zebrafish were induced by arachidonic acid , and the inflammation models were established using LPS and CuSO 4 . The regulatory effects of RMC on the key targets in the pathway of the coagulation-inflammation cascade were investigated by combining ELISA , RT-PCR, and western blot techniques in an attempt to provide multiple validations concerning RMC's pharmacological efficacy and mechanism associated with cooling blood and activating blood circulation. Result The findings from the pharmacodynamic research demonstrated that RMC could inhibit the coagulation and inflammation process of HUVECs. Besides, it lowered the anal temperature and whole blood viscosity in BHS rats in addition to a prolongation of their prothrombin time (PT), thrombin time (TT), and activated partial thromboplastin time (APTT). Successfully constrained thrombotic area and reduced inflammatory cell counts were also observed in zebrafish models. Meanwhile, ELISA, RT-PCR and WB showed that RMC were capable of inhibiting the factors related to coagulation-MARK inflammation pathway—FⅡ, TF, FⅦ, FⅧ, FⅩ, and PAI, as well as down-regulating the expression of IL-6, COX-2, iNOS, TNF-α, ERK, JNK and p38. Conclusion RMC exerts blood-activating and anti-inflammatory effects through regulating the target genes of the coagulation-MARK inflammation cascade pathway.
研究领域:
民族药理学
·
药理学
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中药
·
细胞生物学
·
动物模型
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ORAL PATHOLOGY & MEDICINE
·
2021
·Vol. 51
·期 1
·74-85
·
IF 4.253
Jing-Ya Yang,Fang Wang,Gang Zhou
Background Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory disease with uncertain aetiology. Mucosal-associated invariant T (MAIT) cells and γδT cells are unconventional, innate-like T cells with immunoregulatory capacity. This study aimed to investigate the potential effects of MAIT and γδT cells on the pathogenesis of OLP. Methods Circulating MAIT cells and γδT cells were identified using flow cytometry. Surface proteins including CD4, CD8, CD69, CD103, CD49d, programmed death-1 (PD-1) and its ligand PD-L1 were assessed. Cytokines containing interleukin (IL)-4, IL-17, interferon (IFN)-γ, granzyme B and tumour necrosis factor (TNF)-α released by MAIT and γδT cells were measured following PMA and ionomycin stimulation. Results Circulating MAIT and γδT cells were deficient in OLP. The percentage of CD4 + , CD69 + , CD103 + and PD-1 + MAIT cells was increased in OLP, while that of CD8 + and CD49d + MAIT cells was decreased. The percentage of CD103 + , PD-1 + and PD-L1 + γδT cells was upregulated in OLP. Both the MAIT and γδT cells in OLP produced less IL-4 than controls. The granzyme B-producing MAIT cells were increased, while γδT cells secreting granzyme B and TNF-α were reduced in OLP. IL-17 and IFN-γ in OLP MAIT and γδT cells were not significantly different from that in controls. The frequency of OLP MAIT cells and the MAIT/γδT rate were positively associated with the disease severity. Conclusion The deficient MAIT and γδT cells expressing functional proteins and releasing cytokines may play an immunoregulatory role in the pathogenesis of OLP.
研究领域:
免疫学
·
炎症
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口腔疾病
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）