Gastroenterology Research and Practice
·
2020
·
IF 1.806
Guo-xiang Wang,Yan-li Xiang,Hong-gang Wang,Yang-de Miu,Guang Yu
Evodiamine (Evo) is an indole alkaloid extracted from the traditional Chinese medicinal herb Evodia rutaecarpa. Evo may regulate gastrointestinal motility, but the evidence is insufficient, and the mechanisms remain unknown. The aim of this study was to investigate the effect of Evo on colonic motility of rats and the underlying mechanisms in vitro. Rat colonic muscle was exposed to Evo (10 and 100 μM) followed by immunohistochemistry of cholecystokinin receptor 1 (CCK1R). Muscle contractions were studied in an organ bath system to determine whether CCK1R, nitric oxide (NO), and enteric neurons are involved in the relaxant effect of Evo. Whole-cell patch-clamp was used to detect L-type calcium currents () in isolated colonic smooth muscle cells (SMCs). CCK1R was observed in SMCs, intermuscular neurons, and mucosa of rat colon. Evo could inhibit spontaneous muscle contractions; NO synthase, inhibitor L-NAME CCK1R antagonist, could partly block this effect, while the enteric neurons may not play a major role. Evo inhibited the peak in colonic SMCs at a membrane potential of 0 mV. The current-voltage (I–V) relationship of L-type calcium channels was modified by Evo, while the peak of the I–V curve remained at 0 mV. Furthermore, Evo inhibited the activation of L-type calcium channels and decreased the peak . The relaxant effect of Evo on colonic muscle is associated with the inhibition of L-type calcium channels. The enteric neurons, NO, and CCK1R may be partly related to the inhibitory effect of Evo on colonic motility. This study provides the first evidence that evodiamine can regulate colonic motility in rats by mediating calcium homeostasis in smooth muscle cells. These data form a theoretical basis for the clinical application of evodiamine for treatment of gastrointestinal motility diseases.
研究领域:
药理学
·
生理学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Hui Liu,Huiting Xu,Zhaofeng Song,Zhengwen Li,Saiwei Zhang,Yili Zhang,Jixiang Wang,Xiaoyong Qian
The types and concentrations of L- and D-type amino acids (AAs) produced by sludge hydrolysis increased with increasing pH of alkali treatment, with the highest content of cysteine and a higher degree of racemization of threonine, cysteine, and alanine. There was a strong correlation between methane production and the following AAs (D-leucine, D-aspartic acid, L-threonine, and L-cysteine). The addition of representative AAs (L-cysteine and D-cysteine) increased cumulative methane production, and L-type promoted better than D-type, with the highest cumulative methane production 906.3 mL/g-VS with the addition of 50 mg/L of L-cysteine, which was 1.20 times that of the CK group (digestion time 21 d); while the methane production with the addition of 200 mg/L of L-cysteine would be inhibited. The L-type AAs promoted better than the D-type in the solubilization, hydrolysis, acidification, and hydrogen-consumption methanogenesis stages, whereas the homoacetogenesis process and acetate-consumption methanogenesis stages did not play a significant role. The dominant genera of bacteria at the genus level belonged to unclassified_c_Acitinobacteria, unclassified_p_Chloroflexi, unclassified_c_Acidimicrobiia and Mycobacterium, while Methanothrix and Methanobacterium were the dominant archaea in the digesters. The top 4 metabolic functions were biosynthesis of secondary metabolites, microbial metabolism in diverse environments, biosynthesis of AAs and carbon metabolism. Metagenome results showed that, with L-cysteine addition, enriching Methanothrix and Methanobacterium showed enhanced contribution to the main pathways, especially the biosynthesis of secondary metabolites and carbon metabolism.
研究领域:
环境科学
·
微生物学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
FUEL
·
2024
·
IF 6.7
Zongyang Zhang,Yuping Li,Ze Chen,Fuchao Ji,Xiaohong Liang,Haicheng Xuan,Lina Han,Peide Han
Developing an economical and high-efficiency synthesis pathway of SSZ-13 zeolite is of great significance for the ammonia selective catalytic reduction of nitrogen oxides (NH 3 -SCR of NO x ) reactions. Herein, SSZ-13 zeolite were synthesized using L zeolite as the aluminum source in the presence of a mixed structure directing agent (SDA) composed of N,N,N, trimethtyl-1-adamantammonium hydroxide (TMAdaOH) and tetraethylammonium hydroxide (TEAOH). This synthesis strategy aims to accelerate the crystallization rate through interzeolite transformation, while less expensive TEAOH can play a cooperative structure-directing role, thus reducing the consumption of expensive TMAdaOH template. The results showed that pure SSZ-13 zeolites with high crystallinity can be obtained from L zeolite within 12 h at 160 ℃ under low TMAdaOH/SiO 2 ratio of 0.05 (too low to carry out the synthesis on its own in the current synthesis system) in the presence of TEAOH. Moreover, the crystallization mechanism was also investigated by XRD, FT-IR, SEM and TG-DTG techniques. It was proposed that the crystallization of SSZ-13 occurs through the formation of SSZ-13 nuclei under the direction of TMAdaOH and promotion of TEAOH, subsequently TMAdaOH was incorporated in the framework to further induce the crystal growth of SSZ-13. Especially, the zeolite crystal size can be modulated by the amount of TEAOH added. In addition, After Cu 2+ exchange, the obtained Cu-SSZ-13 sample exhibits superior catalysis performance in the NH 3 -SCR of NO x reaction, and the NO x conversion rate remained over 90 % across a broad range from 200 to 600 °C, demonstrating its significant application potentials in NO x removal from diesel vehicle exhausts.
研究领域:
材料科学
·
环境科学
·
催化化学
✓ 已验证
DOI
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
·
2017
·
IF 3.498
Zhuo Fan,Nanying Lv,Xiao Luo,Wen Tan
Cardiac hypertrophy is a thickening of the heart muscle that is associated with cardiovascular diseases such as hypertension and myocardial infarction. It occurs initially as an adaptive process against increased workloads and often leads to sudden arrhythmic deaths. Studies suggest that the lethal arrhythmia is attributed to hypertrophy-induced destabilization of cardiac electrical activity, especially the prolongation of the action potential. The reduced activity of I to is demonstrated to be responsible for the ionic mechanism of prolonged action potential duration and arrhythmogeneity. Isosteviol (STV), a derivative of stevioside, plays a protective role in a variety of stress-induced cardiac diseases. Here we report effects of STV on rat ISO-induced hypertrophic cardiomyocytes. STV alleviated ISO-induced hypertrophy of cardiomyocytes by decreasing cell area of hypertrophied cardiomyocytes. STV application prevented the prolongation of action potential which was prominent in hypertrophied cells. The decrease and increase of current densities for I to and I CaL observed in hypertrophied myocytes were both prevented by STV application. In addition, the results of qRT-PCR suggested that the changes of electrophysiological activity of I to and I CaL are correlated to the alterations of the mRNA transcription level.
研究领域:
药理学
·
心血管病学
✓ 已验证
DOI
PubMed
高影响因子
TALANTA
·
2018
·
IF 4.244
Yiting Pan,Qinzhen Li,Qin Zhou,Wan Zhang,Ping Yue,Changzhi Xu,Ximing Qin,Haizhu Yu,Manzhou Zhu
Benefiting from the excellent photostability and biocompatibility, fluorescent nanoclusters have recently emerged as a highly attractive bio-sensing and imaging material, especially in early diagnosis of cancer. However, their clinic applications were limited by the unsatisfactory specificity and the complex synthesis. In this study, novel methionine coated gold nanoclusters (Met-AuNCs) have been prepared via an easily-achievable one-pot synthetic method. The prepared Met-AuNCs showed high imaging-specificity: after incubating with Met-AuNCs for 1 h, cancer cells (including A549, Hela, MCF-7, HepG2) were fluorescent, while the normal cells (WI-38 and CHO) showed no fluorescence. According to a series of controlled experiments, the reason for the high imaging-selectivity was proposed to originate from the specific recognition of L-type amino acid transporter overexpressed in cancer cells.
研究领域:
纳米技术
·
癌症生物学
·
生物成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Reports Methods
·
2024
·
IF 4.3
Jinli Geng,Yaxiong Yang,Boying Li,Zhen Yu,Shuang Qiu,Wen Zhang,Shixin Gao,Nan Liu,Yi Liu,Bo Wang,Yubo Fan,Chengfen Xing,Xiaodong Liu
Genetically encoded inhibitors of Ca V 1 channels that operate via C-terminus-mediated inhibition (CMI) have been actively pursued. Here, we advance the design of CMI peptides by proposing a membrane-anchoring tag that is sufficient to link the inhibitory modules to the target channel as well as chemical and optogenetic modes of system control. We designed and implemented the constitutive and inducible CMI modules with appropriate dynamic ranges for the short and long variants of Ca V 1.3, both naturally occurring in neurons. Upon optical (near-infrared-responsive nanoparticles) and/or chemical (rapamycin) induction of FRB/FKBP binding, the designed peptides translocated onto the membrane via FRB-Ras, where the physical linkage requirement for CMI could be satisfied. The peptides robustly produced acute, potent, and specific inhibitions on both recombinant and neuronal Ca V 1 activities, including Ca 2+ influx-neuritogenesis coupling. Validated through opto-chemogenetic induction, this prototype demonstrates Ca 2+ channel modulation via membrane-assisted molecular linkage, promising broad applicability to diverse membrane proteins.
研究领域:
神经科学
·
分子生物学
·
生物工程
✓ 已验证
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2015
·Vol. 39
·期 5
·4154-4161
·
IF 3.086
Lei Chen,Bing Yan
A series of novel multi-component photofunctional hybrid materials were assembled using lanthanide (Ln) polyoxometalates (Na9LnW10O36·32H2O, for LnW10, Ln = europium (Eu), terbium (Tb), samarium (Sm) or dysprosium (Dy)), ionic liquids (IMCl) and functionalized zeolite A/L through an inside–outside double modification path. Firstly, the zeolite A/L was functionalized with Ln complexes (Eu-thenoyltrifluoroacetone (TTA) or Tb-trifluoroacetylacetone (TAA)) using the ion-exchange treatment and “ships in a bottle” dispersion. Then, 1-methyl-3-(trimethoxysilyl)propyl chloride (IM+Cl−) was covalently grafted onto the functionalized zeolite A/L and linked to Ln polyoxometalates as a double linker. These hybrids have two luminescence centers, one is Ln complexes, and the other is Ln polyoxometalates. By adjusting the different components of the hybrids, the luminescent tuning and integration of various colors (white, warm-white, green and red light) can be realized. These results can be expected to have potential application in appropriate fields.
研究领域:
材料科学
·
化学
·
光学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Guo-Xuan Liu,Fan Diao,Guang Lu,Qiang Zheng,Bin Fu,Hua-Chen Jiao,Ke-Zhou Wang,Dong-Hai Liu
Alectinib is the first-line therapy for anaplastic lymphoma kinase rearranged non-small cell lung cancer globally. Sinus bradycardia, as the major adverse cardiac events of alectinib, still widely impact patient’s quality of life. However, its underlying mechanism remains elusive. The aim of this study was to reveal the pathogenesis of the alectinib induced sinus bradycardia (AISB) in a rat model, including the electrophysiology alterations and the molecular mechanism. SD rats were administered alectinib (10 mg / kg / day) by gavage for 7 to 10 days to mimic the clinical AISB. 3-days alectinib treatment did not change heart rate and sinus node recovery time (SNRT) as assessed through in vivo electrophysiology study. Also, alectinib didn’t influence automaticity in isolated heart or single sinus node cardiomyocytes, indicating alectinib cannot decrease sinus node function rapidly. The decreased heart rate and prolonged SNRT was found after 7-days alectinib treatment. The inducibility of atrial fibrillation was not affected under the same condition. The RNA-seq assay revealed the transcriptomic alterations in sinus node of alectinib treated rats, and the dysregulation of genes in cardiac function were observed. The decreased expression of L-type calcium channel Cacna1d was confirmed among the channel candidates identified from RNA-seq assay. Subsequently, the patch-clamp test revealed the reduction in the corresponding L-type calcium current density in 7-days alectinib treated rats. These findings revealed that the AISB was caused by the reduction in Cacna1d expression which resulted in the electro-dysfunction mediated by the suppressed I CaL .
研究领域:
肿瘤学
·
心脏病学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2023
·
IF 9.9
Zhang Yufei,Cheng Qian,Xue Yuhao,Yao Kai,Syeda Madiha Zahra,Xu Jian,Wu Jianheng,Wang Zhenjie,Tang Longguang,Mu Qingchun
Glioma is the most common primary craniocerebral tumor caused by the cancerous growth of glial cells in the brain and spinal cord. Currently, standard treatment is the surgical resection followed by concurrent radiation and chemotherapy. However, the blood-brain barrier (BBB) prevents most antitumor drugs from entering the brain and reduces their efficacy, especially in low-grade glioma. Since L-type amino acid transporter 1 (LAT1) is highly expressed in glioma cells and mediates drug transport across the BBB, it is a promising target for drug delivery and treatment of glioma. Temozolomide (TMZ) is the first-line treatment for glioma, however, patients often exhibit drug resistance at advanced stage. A multikinase inhibitor and inducer of ferroptosis, sorafenib can improve the therapeutic effects of TMZ. Therefore, to optimize the glioma treatment and cross the BBB, we designed LAT1-targeting nanoparticles co-loaded with TMZ and sorafenib. Our results from both in vitro and in vivo studies confirmed that LAT1-targeting nanoparticles significantly increased the cellular uptake, cytotoxicity, accumulation at tumor site, and the anti-tumor efficacy compared to the non-target nanoparticles. Therefore, LAT1 can be used as a potential target for brain-targeted drug delivery, and sorafenib-induced ferroptosis can aid the anti-glioma efficacy of TMZ.
研究领域:
肿瘤学
·
神经科学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Dongxu Wang,Kai Yin,Yue Zhang,Hongmin Lu,Lulu Hou,Hongjing Zhao,Mingwei Xing
Endemic fluorosis (EF) has been listed as one of the serious public health problems in many countries. Long-term exposure to high fluoride can lead to severe neuropathological damage to the brain. Although long-term research has revealed the mechanism of some brain inflammation caused by excessive fluoride, the role of intercellular interactions, especially immune cells, in brain damage is still unclear. Fluoride can induce ferroptosis and inflammation in the brain in our study. A co-culture system of neutrophil extranets and primary neuronal cells showed that fluoride can aggravate neuronal cell inflammation by causing neutrophil extranets (NETs). In terms of the mechanism of action, we found that fluoride leads to the opening of calcium ion channels by causing neutrophil calcium imbalance, which in turn leads to the opening of L-type calcium ion channels (LTCC). Extracellular free iron enters the cell from the open LTCC, leading to neutrophil ferroptosis, which releases NETs. Blocking LTCC (nifedipine) rescued neutrophil ferroptosis and reduced the generation of NETs. Inhibition of ferroptosis (Fer-1) did not block cellular calcium imbalance. In summary, our study explores the role of NETs in fluoride-induced brain inflammation and suggests that blocking calcium channels may be one of the possibilities to rescue fluoride-induced ferroptosis.
研究领域:
神经科学
·
免疫学
·
毒理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2024
·
IF 4.4
Jianbo Li,Ertai Ye,Jingwen Huang,Meng Xu,Jieke Zhang,Junrong Zhang,Huijie Cai,Jinjie Zhang
The timely suppression of inflammatory mediator production and mitigation of their effects on pancreatic acinar cells are crucial for the successful management of acute pancreatitis . To achieve effective treatment, we present a novel approach utilizing cysteine modified PEG nanoparticles for both precise accumulation at the site of pancreatitis and specific targeting of acinar cells. Methylprednisolone , a nonsteroidal anti-inflammatory drug, was tailored to enhance its circulation time in the bloodstream, preferentially accumulate in the pancreas and enhance cell uptake efficiency by acinar cells through specifically targeting L-Type amino acid transporter 1. The nanosystem significantly downregulated pro-inflammatory cytokines in plasma, resulting in the effective suppression of inflammation in acinar cells within an acute pancreatitis rat model. The utilization of the dual targeted therapy strategy holds considerable potential for the clinical management of pancreatitis.
研究领域:
药学
·
纳米技术
·
炎症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Liu Tao,Cui Lijuan,Xue Huan,Yang Xiaohua,Liu Mengmeng,Zhi Linping,Yang Huanhuan,Liu Zhihong,Zhang Min,Guo Qing,He Peifeng,Liu Yunfeng,Zhang Yi
Angiotensin II type 1 (AT1) receptor blockers (ARBs), as antihypertensive drugs, have drawn attention for their benefits to individuals with diabetes and prediabetes. However, the direct effects of ARBs on insulin secretion remain unclear. In this study, we aimed to investigate the insulinotropic effect of ARBs and the underlying electrophysiological mechanism. We found that only telmisartan among the three ARBs (telmisartan, valsartan, and irbesartan) exhibited an insulin secretagogue role in rat islets. Independent of AT1 receptor and peroxisome proliferator-activated receptor γ (PPARγ), telmisartan exerted effects on ion channels including voltage-dependent potassium (Kv) channels and L-type voltage-gated calcium channels (VGCCs) to promote extracellular Ca2+ influx, thereby potentiating insulin secretion in a glucose-dependent manner. Furthermore, we identified that telmisartan directly inhibited Kv2.1 channel on a Chinese hamster ovary cell line with Kv2.1 channel overexpression. Acute exposure of db/db mice to a telmisartan dose equivalent to therapeutic doses in humans resulted in lower blood glucose and increased plasma insulin concentration in OGTT. We further observed the telmisartan-induced insulinotropic and electrophysiological effects on pathological pancreatic islets or β-cells isolated from db/db mice. Collectively, our results establish an important insulinotropic function of telmisartan distinct from other ARBs in the treatment of diabetes.
研究领域:
药理学
·
内分泌学
·
糖尿病
·
电生理学
✓ 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）