Food Bioscience
·
2019
·
IF 3.22
Chun-Min Ma,Tie-Jing Li,Xin-Huai Zhao
Lactoferrin hydrolysates (LF-H) were digested using pepsin and modified using a pepsin-catalyzed plastein reaction with tryptophan (Trp) to obtain a target product. LF-H, the target product, plastein reaction-modified LF-H alone, and a mixture of LF-H and Trp were evaluated for their activities with human gastric cancer BGC-823 cells at 24 and 48 h. Assay results indicated that the target product had decreased free amino groups and had incorporated Trp. LF-H and the plastein reaction-modified LF-H alone did not show detectable growth inhibition on BGC-823 cells at 1–3 mg/mL; however, the target product at the same dose levels inhibited cell growth, and showed higher activity than the mixture ( P < 0.05). The target product at 2 and 3 mg/mL stopped cell cycle progression at the G0/G1-phase, induced DNA fragmentation , and showed apoptosis induction, which increased the number of apoptotic cells. Moreover, time- and dose-dependent responses were observed in these experiments. RT-PCR assay results indicated that exposure of the cells to the target product resulted in up- and down-regulated mRNA expression for 7 apoptosis-related genes, namely Bcl-2, Bcl-xl, Bad, Bax, caspase-3, caspase-6, and caspase-9. Thus, the plastein reaction increased in vitr o anticancer activities of LF-H with BGC-823 cells, and more importantly, both the plastein reaction and Trp incorporation contributed to enhanced activities.
研究领域:
生物化学
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癌症研究
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分子生物学
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产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Yuling Tong,Ruilin Wang,Xia Liu,Miao Tian,Yanling Wang,Yanfei Cui,Wenjun Zou,Yanling Zhao
Ethnopharmacological relevance Zuojin Pill (ZJP) is a classic prescription composed of Coptis chinensis and Tetradium ruticarpum (A.Juss.) T.G.Hartley, which is often used in the treatment of digestive system diseases . Aim of this study The purpose of this study was to explore the therapeutic effect and potential mechanism of ZJP on chronic atrophic gastritis (CAG) induced by MNNG . Materials and methods The GES-1 and rat model of CAG was established by MNNG. Detection of cell viability, morphological changes and proliferation of GES-1 by CCK-8 and high content screening (HCS) assay. G-17, IL-8 and TNF-α in rat serum were detected by ELISA kit. The expression of related mRNA and protein on TGF-β1/PI3K/Akt signal axis were detected by RT-PCR and Western blot . Results The results showed that ZJP could significantly improve the GES-1 damage induced by MNNG and improve the gastric histomorphology of CAG rats. The intervention of ZJP could significantly reduce the content of G-17 and inflammatory factors IL-8, TNF- α, IL-6 and IL-1β, inhibit the expression of TGF-β1, PI3K and their downstream signals p-Akt, p-mTOR, P70S6K, and promote the expression level of PTEN, LC3-II and Beclin-1. Conclusion ZJP has a good therapeutic effect on CAG induced by MNNG, which may be closely related to the inhibition of TGF-β1/PI3K/Akt signal pathway.
研究领域:
药理学
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民族药理学
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胃肠病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Materials Interfaces
·
2021
·Vol. 8
·期 23
·2101097
·
IF 6.147
Kelin Zhang,Qilin Zhang,Mingxia Yu,Zixiang Wang,Qingyuan Song,Cuiwen Zhu,Xianjia Wu,Rongxiang He,Xingzhong Zhao
A low cost and easily fabricated 3D micro-nano biocompatible calcium phosphate (CaP) microstructure platform is developed to efficiently capture and non-destructively release cancer cells. The thickness of CaP is ≈3 µm after 2.5 min deposition and increased to ≈12 µm after 10 min deposition. The void size between CaP nanosheets is increased when the electro deposition time is increased. This micro-nano bio-interface is suitable for cancer cell capturing and culturing. More than 90% for the EpCAM positive cells are captured on the CaP substrates where the specific anti-EpCAM antibody is modified. On the other hand, the CaP substrates are easily degraded in citric acid (pH 6.0). In this method, 80% of the captured cancer cells can be rapidly released in 2.5 min on the 3 µm thick CaP substrates. The released cancer cells can be well cultured and can keep their viability. This platform is successfully used to capture the CTCs from patients’ peripheral blood with different kinds of cancer. This platform can be applied in the controllable single CTC capture and release analysis, including downstream RT-PCR, gene sequence, and single cell based tumor sphere culture in the future.
研究领域:
生物材料
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生物医学工程
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癌症研究
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纳米技术
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Yang Zheng,Jiaru Wang,Tiejian Zhao,Lei Wang,Jiahui Wang
Ethnopharmacological relevance Curcuma is a common Chinese herbal medicine that is used in the clinical treatment of chronic liver disease . Studies have found that curcumol is the main active ingredient of curcuma and has good hepatoprotective and anti-inflammatory effects. However, there are few reports on the molecular mechanism underlying the anti-liver fibrosis effect of curcumol. Aim To explore the effect of curcumol on liver angiogenesis, and to reveal the mechanism of curcumol against liver fibrosis . Materials and methods We used liver collagenase perfusion combined with Percoll density gradient sedimentation to separate primary liver sinusoidal endothelial cells, and then applied a leptin-activated cell pathological model. The cells were divided into four treatment groups as follows: blank group, model group, curcumol group, and solafini group. MTT was used to detect the cell proliferation rate in each group, and RT-PCR and western blotting were used to detect the expressions of VEGF, AKT, eNOS , CD31, and vWF. A fluorescent probe was used to detect NO expression, and scanning electron microscopy was used to observe changes in the cell fenestration structure. Angiogenesis assays were used to observe blood vessel formation in each group. Results The results of the MTT test found that the proliferation rate of each group was higher. The results of the molecular biology tests found that curcumol inhibited the activity of the VEGF/AKT/eNOS pathway, thereby increasing fenestration of sinusoidal endothelial cells and inhibiting liver angiogenesis. These differences were statistically significant compared with the model group. Conclusions Curcumol inhibits the activity of the VEGF/AKT/eNOS signaling pathway, regulates the structure of hepatic sinusoidal endothelial cells, and inhibits liver angiogenesis, which together may explain its anti-liver fibrosis mechanism.
研究领域:
药理学
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分子生物学
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肝病学
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民族药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2022
·
IF 5.545
Li-Na Ke,Ling-Qi Kong,Xiu-Lian Zhu,Feng-Xu Wu,Qin-Hua Chen,Bin Li,Yun Dong,Hong-Mei Wang,Xiao-Hua Zeng
We have synthesized Rhopaladins’ analog (2E,4E)-4-chlorobenzylidene-2-(4-chlorostyryl)-N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide (RPDPRH) via a highly facile, inexpensive and green approach and verified the structural superiority of compound RPDPRH through molecular docking. Moreover, we further detected the anti-proliferation, apoptosis and HPV E6/E7 effects of RPDPRH on CaSki cells. Finally, we confirmed that compared with the previous compound (E)-N-(tert-butyl)-2-(4-chlorobenzoyl)-4-(4-fluorobenzylidene)-1-isopropyl-5-oxopyrrolidine-2-carboxamide (RPDPB), RPDPRH could better inhibit proliferation, induce apoptosis, and down-regulate HPV E6/E7 mRNA expression on Caski cells. And preliminary RT-PCR experiments have demonstrated that RPDPRH also could affect the expression of Bcl-2, Bax and Caspase-3 mRNA in Caski cells. In summary, RPDPRH has potential as an effective agent against cervical cancer and will play an important role in our subsequent research.Keywords: 4-arylidene-5-oxopyrrolidine, green synthesis, molecular docking, anti-tumor activity, apoptosis
研究领域:
化学
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药理学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Xiao-xiao Zheng,Ding-xiang Li,Ya-ting Li,Yu-lang Chen,Yan-lin Zhao,Shuai Ji,Meng-zhe Guo,Yan Du,Dao-Quan Tang
Elevations in circling branched-chain amino acids (BCAAs) levels associated with insulin resistance and type 2 diabetes mellitus (T2DM). Morus alba L. water extracts (MLE) show hypoglycemic function, but the precise mechanism remains obscure. This study is designed to investigate the association of the antidiabetes effect of MLE with the BCAAs co-metabolism modulated by host and gut microbiota. Tissue-specific expressions of BCAA-catabolizing enzymes were detected by RT-PCR and western blot, respectively. The components of the intestinal microflora were analyzed by high-throughput 16S rRNA gene sequencing. The results showed that MLE administration improved blood glucose and insulin level, decreased inflammatory cytokines expression, and lowered serum and feces BCAAs levels. Furthermore, MLE reversed the abundance changes of the bacterial genera correlated with serum and feces BCAAs, such as Anaerovorax , Bilophila , Blautia , Colidextribacter , Dubosiella , Intestinimonas , Lachnoclostridium , Lachnospiraceae_NK4A136 , Oscillibacter , and Roseburia . Functionality prediction indicated that MLE potentially inhibited bacterial BCAAs biosynthesis, and promoted the tissue-specific expression of BCAAs catabolic enzyme. More importantly, MLE had obvious impacts on BCAA catabolism in germ-free-mimic T2DM mice. Those results indicated that MLE improving T2DM-related biochemical abnormalities is associated with not only gut microbiota modification but also the tissue-specific expression of BCAAs catabolic enzyme.
研究领域:
药理学
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糖尿病研究
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微生物学
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分子生物学
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产品关联
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
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药理学
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中药
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细胞生物学
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动物模型
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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
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产品关联
DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2022
·
IF 12.545
Xiangqin Meng,Sijia Zou,Dandan Li,Jiuyang He,Ling Fang,Haojue Wang,Xiyun Yan,Demin Duan,Lizeng Gao
The coronavirus disease 2019 (COVID-19) pandemic has created a huge demand for sensitive and rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current gold standard for SARS-CoV-2 detection is reverse transcription-polymerase chain reaction (RT-PCR)-based nucleic acid amplification. However, RT-PCR is time consuming and requires specialists and large instruments that are unattainable for point-of-care testing (POCT). To develop POCT for SARS-CoV-2, we combined recombinase polymerase amplification (RPA) and FeS 2 nanozyme strips to achieve facile nucleic acid amplification and subsequent colorimetric signal enhancement based on the high peroxidase-like activity of the FeS 2 nanozymes. This method showed a nucleic acid limit of detection (LOD) for SARS-CoV-2 of 200 copies/mL, close to that of RT-PCR. The unique catalytic properties of the FeS 2 nanozymes enabled the nanozyme-strip to amplify colorimetric signals via the nontoxic 3,3′,5,5′-tetramethylbenzidine (TMB) substrate. Importantly, the detection of clinical samples of human papilloma virus type 16 (HPV-16) showed 100% agreement with previous RT-PCR results, highlighting the versatility and reliability of this method. Our findings suggest that nanozyme-based nucleic acid detection has great potential in the development of POCT diagnosis for COVID-19 and other viral infections.
研究领域:
分子生物学
·
病毒学
·
即时诊断
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2019
·
IF 5.256
Lina Wu,Yingfei Wang,Rong He,Yue Zhang,Yuling He,Chao Wang,Zhenda Lu,Ying Liu,Huangxian Ju
Despite the great success of fluorescence sensing array application in bioanalysis , the photo-quenching problem accompanied with high surface fluorophore density has become the bottleneck for its further sensitivity improvement. Herein, a fluorescence polyethylene glycol (PEG) hydrogel array was developed for highly sensitive microRNA detection based on interfacial cation exchange amplification coupled with DNA hybridization chain reaction (HCR). The carboxylate PEG hydrogel array was fabricated on glass slide via photo polymerization and modified with miRNA capture probe, target miRNA binding triggered HCR in hydrogel with biotin labelled DNA probes to generate numerous DNA polymer chains where biotinylated CdS QDs were subsequently conjugated with a streptavidin bridge. Interfacial cation exchange amplification was triggered in hydrogel upon the introduction of Ag + and Rhod-5N, and abundant Cd 2+ was released from CdS to bind with Rhod-5N for substantial fluorescence enhancement. The aqueous-like environment of hydrogel eliminated the fluorescence quenching and simplified experiment process by performing cation exchange reaction at interface with direct result. The linear range for model target miRNA-21 was 1 fM to 500 pM with a detection limit of 0.835 fM. Taking advantage of the nonfouling property of PEG hydrogel, direct quantification of miRNA-21 was achieved from crude cancer cell lysates with a detection limit down to 10 equivalent cells. The expressions of circulating miRNA-21 in clinical serum samples were also assessed with comparable results from RT-PCR. The developed hydrogel array provides a universal platform for highly sensitive fluorescence sensing, and would benefit clinical non-invasive disease diagnosis.
研究领域:
生物化学
·
生物技术
·
分析化学
·
分子生物学
·
临床诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
IF 4.152
Zhiyuan Li,Liu Zhang,Quanshun Li
Herein, N -acetyl- l -leucine-modified polyethylenimine was successfully constructed through the EDC/NHS-mediated coupling reaction and employed as vectors to accomplish p53 gene delivery using HeLa (p53wt) and PC-3 cells (p53null) as models. Compared with PEI25K, the derivatives exhibited lower cytotoxicity, protein adsorption and hemolytic activity, together with satisfactory pDNA condensation capability and gene transfection efficiency. After p53 transfection, MTT analysis confirmed that the cell proliferation was inhibited. Flow cytometric analysis showed that the derivative-mediated p53 delivery could induce stronger early apoptosis than PEI25K and Lipofectamine 2000 . Further, PC-3 cells showed higher sensitivity to the exogenous p53 transfection than HeLa cells. The mechanism for inducing apoptosis was determined to be up-regulation of p53 expression at both mRNA and protein levels using RT-PCR and western blotting analysis. Expression level and activity analysis of caspase-3, -8 and -9, and mitochondrial membrane potential measurement revealed that p53 transfection mediated by these derivatives facilitated early apoptosis of tumor cells via a mitochondria-dependent apoptosis pathway. Thus, the derivatives showed potential as biocompatible carriers for realizing effective tumor gene therapy.
研究领域:
癌症生物学
·
分子生物学
·
基因治疗
·
药学
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产品关联
DOI
PubMed
高影响因子
DIGESTIVE DISEASES AND SCIENCES
·
2023
·Vol. 68
·期 6
·2414-2426
·
IF 3.1
Lin Mengjuan,Hu Guiying,Wang Zhengqiang,Yu Baoping,Tan Wei
Background The mechanism underlying irritable bowel syndrome (IBS), a common disease with hyperalgesia, remains elusive. The spinal cholinergic system is involved in pain modulation, but its role in IBS is unknown. Aims To determine whether high-affinity choline transporter 1 (CHT1, a major determinant of the cholinergic signaling capacity), is implicated in spinal modulation of stress-induced hyperalgesia. Methods A rat IBS model was established by water avoidance stress (WAS). Visceral sensations were detected by abdominal withdrawal reflex (AWR) and visceromotor response (VMR) to colorectal distension (CRD). Abdominal mechanical sensitivity was determined by von Frey filaments (VFFs) test. RT-PCR, Western blot, and immunostaining were performed for spinal CHT1 expression. Spinal acetylcholine (ACh) was measured by ELISA; the influence of spinal CHT1 on hyperalgesia were evaluated by intrathecal administration of MKC-231 (a choline uptake enhancer) and hemicholinium-3 (HC-3, a specific inhibitor of CHT1). Minocycline treatment was used to explore the role of spinal microglia in hyperalgesia. Results After 10 days of WAS, AWR scores and VMR magnitude to CRD, and the number of withdrawal events in VFF test were increased. Double-labeling showed that CHT1 in the dorsal horn was expressed in most of the neurons and almost all the microglia. The CHT1 expression and ACh levels in the spinal cord and the density of CHT1-positive cell in the spinal dorsal horn were enhanced in WAS-exposed rats. HC-3 enhanced pain responses in WAS rats; MKC-231 alleviated pain in WAS rats by upregulating CHT1 expression and increasing ACh production in the spinal cord. Furthermore, microglial activation in the spinal dorsal horn promoted the stress-induced hyperalgesia, and MKC-231 achieved analgesic effects by inhibiting the spinal microglial activation. Conclusions CHT1 exerts antinociceptive effects in spinal modulation of chronic stress-induced hyperalgesia by increasing ACh synthesis and suppressing microglial activation. MKC-231 has potential for treating disorders accompanied by hyperalgesia.
研究领域:
神经科学
·
疼痛研究
·
胃肠病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）