BIOCHEMICAL PHARMACOLOGY
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2022
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IF 6.1
Yuanxing Zhi,Jin Liu,Peihua Kuang,Xin Zhang,Ziwei Xu,Yanshan Chen,Xiuling Lin,Xiaoyan Wu,Pingzheng Zhou,Jianjun Chen
The enzyme cyclic GMP-AMP synthase (cGAS) senses cytosolic DNA and catalyzes the formation of 2′3′-cyclic-GMP-AMP (cGAMP), which in turn triggers interferon (IFN) production. Inappropriate activation of cGAS and production of cGAMP have been linked to a diversity of autoimmune diseases. The volume-regulated anion channels (VRACs) have been recently demonstrated to permeate cGAMP, thus making the channel essential for the activation of the cGAS-cGAMP-STING axis. DCPIB, a prominent inhibitor of VRAC channel, has been recently reported to also significantly activate TREK1 channel. Herein, in this study, we have designed and synthesized a series of novel DCPIB derivatives and investigated their potential regulatory effects on VRAC/TREK1 channels. Our results manifested that compound 6u was a dual inhibitor of VRAC/TREK1 channels with IC 50 s of 7.11 ± 0.94 μM and 4.43 ± 0.90 μM, respectively. On top of that, our data demonstrated that 6u impaired interferon production in a concentration-dependently manner by dampening cGAS-cGAMP-STING pathway without any cytotoxicity when it comes to herpes simplex virus type 1 (HSV1) infection. To sum up, our study not only discovered a novel DCPIB analog with dual inhibitory effects on VRAC/TREK1 channels but also provided a new strategy for the design and development of newly potent VRAC inhibitors, which benefits the treatment of cGAS-STING related autoimmune and inflammatory diseases .
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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化学
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DOI
PubMed
高影响因子
Acta Cardiologica Sinica
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2018
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IF 0.927
Li-Tan Yang,Yao-Mao Chang,Tsung-Han Hsieh,Wen-Hsuan Hou,Chung-Yi Li
Background We conducted a time-series analysis of daily ambient temperature and all-cause, cardiovascular, and respiratory disease mortality in Taiwan, which is generally neither extremely hot nor cold. Methods Data on all-cause daily mortality rates (excluding accidents, suicide, and homicide), and mortality rates due to respiratory and cardiovascular diseases between 2008 and 2010 were obtained from the Taiwan Death Registry. The daily temperature for that period was averaged from 33 monitoring stations nationwide. A generalized least square model was constructed to assess the relationship between the time-series trends of temperature and mortality, and the cross-correlation function was used to determine the possible time lag for the effect of temperature on mortality. Results As the average temperature increased, the daily all-cause (β = -0.006) and respiratory disease (β = -0.012) mortality rates decreased. On the other hand, an inverse relationship (β = -0.028) between average daily temperature and cardiovascular disease mortality was observed only for a temperature between 12.91 °C and 26.36 °C. The time lag for all-cause and cardiovascular disease mortality was similar at 4-6 days, while the lag for respiratory disease was longer at 13-16 days. Conclusions We found inverse associations between average temperature and all-cause and respiratory mortality. An inverse association between temperature and cardiovascular disease mortality was observed only from 12.91 °C to 26.36 °C.
研究领域:
流行病学
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环境医学
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公共卫生
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心血管病学
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呼吸病学
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PubMed
高影响因子
AAPS PHARMSCITECH
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2024
·Vol. 25
·期 7
·1-19
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IF 3.4
Long Yanqiu,Lei Fang,Hu Jie,Zheng Zhiyun,Gui Shuangying,He Ning
The compound Salvia Recipe has been shown to have a relatively significant curative effect in management of cardiovascular and cerebrovascular diseases. This work aimed to prepare a thermosensitive in situ gel (ISG) delivery system that utilizes Poloxamer 407, Poloxamer 188, and hydroxypropyl methylcellulose for ocular administration of the compound Salvia recipe to treat cardiovascular and cerebrovascular diseases. The central composite design-response surface method was utilized to improve the prescription of the gel. The formulated gel was characterized and assessed in terms of stability, retention time, in vitro release, rheology, ocular irritation, pharmacokinetics studies, and tissue distribution. The gel was a liquid solution at room temperature and became semisolid at physiological temperature, prolonging its stay time in the eye. Pharmacokinetics and tissue distribution experiments indicated that thermosensitive ISG had enhanced targeting of heart and brain tissues. Additionally, it could lower drug toxicity and side effects in the lungs and kidneys. The compound Salvia ophthalmic thermosensitive ISG is a promising drug delivery system for the management of cardiovascular and cerebrovascular illnesses. Graphical Abstract
研究领域:
药剂学
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生物医学工程
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眼科药物递送
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DOI
PubMed
高影响因子
Nanoscale
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2019
·Vol. 11
·期 36
·16879-16885
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IF 6.97
Han Ding,Yi An,Tao Zhao,Bing Liu,Yin Wang,Lei Zhang,Yu Wang,Yuan Zhang,Man Wang,Yanhan Dong,Longgang Hu,Bu-Chang Zhao,Peifeng Li
microRNAs are a type of evolutionarily conserved small non-coding RNA with a length of 18–25 nucleotides. In recent years, increasing studies have shown that the content of specific miRNAs in the blood changes significantly during the occurrence and development of major diseases such as cardiovascular disease and cancer. Therefore, miRNAs may serve as important new biomarkers that can be used for disease diagnosis in the future. Here, we improved the polyethylene glycol layer on the surface of a traditional silicon sphere to specifically capture miRNAs by means of a full-function microplate detector, at 100 microliters. The detection limit for specific miRNAs per liter of plasma can reach 1 fM, and simultaneous detection of 96 samples can be achieved. Compared with the traditional real-time PCR technology, our detection eliminates the complex steps of miRNA extraction, reverse transcription, amplification, etc. and avoids more human error in the detection process. Using the full-featured microwell detector, we can rapidly detect specific miRNAs in plasma, which can be used in the diagnosis of cardiovascular diseases in the future.
研究领域:
生物标志物研究
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医学诊断
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分子生物学
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生物技术
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DOI
PubMed
高影响因子
Journal of Analytical Science and Technology
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2024
·Vol. 15
·期 1
·1-8
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IF 2.5
Li Yunxiao,Wang Qiuxia,Wang Yali
The abnormally expressed microRNAs (miRNAs) serve as crucial indicators for disease diagnosis and are strongly associated with the progression of various diseases. The quantification of miRNAs is highly significant for the clinical diagnosis and treatment of various types of cancers. This study utilizes the CRISPR/Cas13a system, which combines CRISPR RNA (crRNA) and CRISPR-associated Cas13a, to recognize the miRNA directly and specifically, thus activating the trans-cleavage activity of Cas13a. By integrating the CRISPR-Cas13a system with an exonuclease-iii (Exo-iii)-assisted chain cleavage of silver ions (Ag+)-aptamer and an Ag+ -based color reaction, a method for the detection of miRNA that is specific and sensitive is developed. This approach demonstrated exceptional sensitivity in detecting miRNA, with a low detection limit of 5.12 fM. Moreover, the suggested method was effectively utilized to precisely measure the amount of miRNA in intricate biological samples, demonstrating its practical applicability. Furthermore, due to its elevated sensitivity and simple probe design and fluorophore labeling, the suggested colorimetric technique holds great potential for use in clinical diagnostics.
研究领域:
分子生物学
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医学诊断
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生物技术
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DOI
高影响因子
Analytical Methods
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2025
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IF 2.6
Haifang Liu,Huayu Han,Leyang Shi,Yong Long,Wenfen Zhang,Yun Chen,Zheng Zhou,Jianbo Liu
Copper plays essential role in human life, as it participates in several physiological processes, such as antioxidant defense, keeping blood vessels integrity, and neurotransmitter synthesis. In the nervous system in particular, copper is essential for neuronal function. Research has shown that alterations in copper levels, either excess or deficiency, may cause neurodegeneration, such as Alzheimer’s disease, Parkinson’s disease, Wilson’s disease, and others. Thus, careful tracking of the levels of copper in serum is important for preventing neurodegeneration. This study reports a new CD-based fluorescence turn-on copper (II) probe with exceptional selectivity, high sensitivity, and considerable enhancement of emission intensity. As a result of these attractive sensing properties, copper ion in serum of patients with neurodegenerative diseases were monitored.
研究领域:
神经生物学
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生物无机化学
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生物传感
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转化医学
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临床诊断
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2020
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IF 4.192
Xiaoyun Jiang,Dingmin Zhang,Yongling Lu,Lishuang Lv
Increasing evidence has identified the unsaturated aldehyde acrolein (ACR) as the potential factor that causes deoxyribonucleic acid cross-linking and the development of chronic diseases. The objective of this study was to investigate the mechanism by which theophylline (TP) scavenges ACR for the first time. TP efficiently scavenged ACR through forming adducts, which was demonstrated in a system in which TP was incubated with ACR at different ratios for different times for liquid chromatography with tandem mass spectrometry. Then, the mono- and di-ACR-TP adducts were purified, and their structures were elucidated by high-resolution mass spectrometry and nuclear magnetic resonance analysis. We found that the ACR residue on mono-ACR-TP further trapped one more ACR and formed di-ACR-TP adducts. Furthermore, mono- and di-ACR-TP had similar time-dependent ACR-scavenging activity to TP. Finally, we demonstrated that green tea, coffee, and cocoa inhibited ACR by trapping ACR to form mono- and di-ACR-TP adducts during the incubation of green tea, coffee, and cocoa with ACR.
研究领域:
食品科学
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毒理学
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生物化学
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DOI
PubMed
高影响因子
Nutrients
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2022
·Vol. 14
·期 11
·2312
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IF 6.706
Shanshan Peng,Zhicheng Du,Yannan He,Feng Zhao,Yujing Chen,Shengchi Wu,Yuantao Hao,Li Cai
Findings on prenatal polyunsaturated fatty acids (PUFA) and offspring allergies have been inconsistent, and the majority of studies have focused on Western populations. This study aimed to investigate the associations between maternal erythrocyte PUFA and offspring allergies in the first 2 years in the Chinese population. We included 573 mother–infant pairs from a birth cohort. Based on the outpatient medical records, we identified the diagnosis and time of offspring allergic disease onset. We measured erythrocyte fatty acids by gas chromatography. Associations were examined using Cox regression. We found that higher maternal total PUFA levels (HR= 0.80; 95%CI: 0.68, 0.94), especially of arachidonic acid (AA) (HR= 0.79; 95%CI: 0.65, 0.97) andn-3 PUFA (HR= 0.77; 95%CI: 0.62, 0.97), were associated with reduced risk of offspring allergies. Similar results were found for eczema. Compared with children without a maternal allergy history, the associations of total PUFA (p= 0.028) andn-6 PUFA (p= 0.013) with offspring allergies were stronger in those with a maternal allergy history. Maternal erythrocyte total PUFA, especially AA, andn-3 PUFA were inversely associated with offspring allergies within 2 years of age. There was a significant interaction between maternal allergy history and maternal PUFA in offspring allergies.Keywords:allergic disease;polyunsaturated fatty acids;offspring;pregnancy
研究领域:
营养学
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流行病学
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儿科学
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DOI
PubMed
高影响因子
JOURNAL OF FLUORESCENCE
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2024
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IF 2.6
Gong Yafei,Fu Yan,Lou Dawei
Abnormal tryptophan (Trp) metabolism can be used as an important indicator of chronic hepatitis, paranoia, Parkinson’s disease and other diseases. Deficiency or excessive accumulation of Cu 2+ can cause diseases such as Wilson’s disease and Alzheimer’s disease. Eu-based metal-organic framework (Eu-MOF) was successfully prepared for fluorescence sensing of Trp and Cu 2+ in an aqueous solution (pH = 7.4). Eu-MOF showed high selectivity and sensitivity for Trp and Cu 2+ with detection limits of 0.22 µM and 0.09 µM and K sv of 6.17 × 103 M − 1 and 2.37 × 10 4 M − 1 respectively. Trp and Cu2+ had overlapped UV absorption spectra with that of Eu-MOF and competed for the excitation light source. Trp also attenuated the antennae effect of organic ligands on Eu-MOF, thus quenching the red fluorescence of Eu-MOF. This study provides insights into the application of MOFs in bioanalysis and diagnostics.
研究领域:
生物分析
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诊断学
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材料科学
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DOI
PubMed
高影响因子
Chinese Medicine
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2020
·Vol. 15
·期 1
·1-14
·
IF 2.96
Yang Yi-Yao,Wu Zhao-Yu,Xia Fang-Bo,Zhang Hao,Wang Xu,Gao Jian-Li,Yang Feng-Qing,Wan Jian-Bo
Background The dry root and rhizome of Ligusticum chuanxiong Hort., or Chuanxiong, has been used as a blood-activating and stasis-removing traditional Chinese medicine for 1000 years. Our previous studies have shown the inhibitory activity on platelet and thrombin (THR) of Chuanxiong. THR and factor Xa (FXa) play significant roles in the coagulation cascade and their inhibitors are of valuable in the treatment of thromboembolic diseases. The aim of the present study is to screen THR and FXa inhibitors from Chuanxiong.Methods Four extracts [ethyl acetate (EA), butanol (BA) and remained extract (RE) from 75% ethanol extract, and water extract (WE)] of Chuanxiong were prepared, and their THR/FXa inhibitory activities were assessed in vitro. Following silica-gel column chromatography (SC), the active EA extract and BA extract was further partitioned, respectively. Their active fractions (EA-SC1 to EA-SC5; BA-SC1 to BA-SC5) were obtained and analyzed by LC–MS. After modeling by the principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA), the specific marker compounds were predicted and identified. Their enzyme inhibitory was assessed in vitro and interactions with THR/FXa were investigated by molecular docking analysis.Results Chuanxiong EA extract showed strong activity against THR and BA extract was more effective in inhibiting FXa activity, and their fractions exhibited obvious difference in enzyme inhibitory activity. Furthermore, marker compounds a–h were predicted by PCA and OPLS-DA, and their chemical structures were identified. Among them, senkyunolide A, Z-ligustilide, ferulic acid and senkyunolide I (IC50 was determined as 0.77 mM) with potential THR inhibitory activity, as well as isochlorogenic acid A with FXa inhibitory activity were screened out. It was found that the four components could interact with the active site of THR, and the binding energy was lower than − 5 kcal/mol. Isochlorogenic acid A were bound to the active site of FXa, and the binding energy was − 9.39 kcal/mol. The IC50 was determined as 0.56 mM.Conclusion sTHR/FXa inhibitory components in different extracts of Chuanxiong were successfully characterized by the method of enzyme inhibition activity assays with ultra performance liquid chromatography-quadrupole time of flight mass spectrometry-based multivariate statistical analysis.
研究领域:
中药学
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生物化学
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药理学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2021
·Vol. 23
·期 1
·416
·
IF 5.924
Jingjing Liu,Wenyang Zhao,Chun Li,Tongyu Wu,Liang Han,Zhuozhou Hu,Xiangxiang Li,Jing Zhou,Xinping Chen
Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them, the most frequent diseases are gastric ulcer (GU) and ulcerative colitis (UC). DSS-induced UC and ethanol-stimulated GU models resemble the pathophysiology of human gastrointestinal disease. The current study was designed to explore the anti-oxidation, anti-inflammation, anti-cell death properties of terazosin, an α-adrenergic receptor antagonist, in vivo and in vitro. Our results indicate that terazosin dramatically activates Pgk1, and upregulates glycose metabolism, evidenced by the enhanced ATP production and higher LDH enzymatic activity. Also, terazosin significantly enhances p-AKT expression and inhibits NF-κB p65 activation through abrogating the phosphorylation of IKBα, as well as lowers Caspase-1 and GSDMD expression. The findings in this study demonstrate that terazosin exhibits anti-inflammatory effects by downregulating NF-κB-GSDMD signal pathway, along with enhancing glycolysis for gastrointestinal disease treatment. Meanwhile, we also find terazosin ameliorates ethanol-induced gastric mucosal damage in mice. Collectively, as a clinical drug, terazosin should be translated into therapeutics for gastrointestinal disease soon.Keywords:terazosin;gastrointestinal disease;anti-inflammation;Pgk1;cell death
研究领域:
药理学
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胃肠病学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Caiying Zhang,Yuelong Li,Abdus Samad,Hongliang He,Huan Ma,Yang Chen,Tengchuan Jin
Kyasanur Forest disease virus (KFDV), a tick-borne flavivirus prevalent in India, presents a serious threat to human health. KFDV NS3 helicase (NS3hel) is considered a potential drug target due to its involvement in the viral replication complex. Here, we resolved the crystal structures of KFDV NS3hel apo and its complex with three phosphate molecules, which indicates a conformational switch during ATP hydrolysis . Our data revealed that KFDV NS3hel has a higher binding affinity for dsRNA , and its intrinsic ATPase activity was enhanced by dsRNA while being inhibited by DNA . Through mutagenesis analysis, several residues within motifs I, Ia, III, V, and VI were identified to be crucial for NS3hel ATPase activity. Notably, the M419A mutation drastically reduced NS3hel ATPase activity. We propose that the methionine-aromatic interaction between residues M419 and W294, located on the surface of the RNA-binding channel, could be a target for the design of efficient inhibitor probes. Moreover, epigallocatechin gallate (EGCG), a tea-derived polyphenol, strongly inhibited NS3hel ATPase activity with an IC 50 value of 0.8 μM. Our computational docking data show that EGCG binds at the predicted druggable hotspots of NS3hel. Overall, these findings contribute to the development and design of more effective and specific inhibitors.
研究领域:
病毒学
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结构生物学
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药物设计
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）