BIOORGANIC CHEMISTRY
·
2024
·
IF 4.5
Linlin Han,Hongyan Tan,Jungjoon Lee,Peng Wang,Yuqing Zhao
Based on the significant biological activities and the remarkable physical and chemical properties of 1 H -1,2,3-triazole pharmacophore, we herein adopted the strategy of click chemistry to combine the triazole fragment and the unique scaffold of 25-OCH 3 -PPD ( AD-1 ) to design a series of potent compounds inducing apoptosis and DNA damage. The anti-proliferative effect was verified by MTT assay and colony formation assay. DNA double-stand breaks (DSBs) were obtained by observing the nuclear focus formation and the protein expression of γ-H2AX. Cell cycle arrest was evaluated by the cycle-related proteins such as CDK2, CDK4, CDK6, Cyclin D1 and P 21. Apoptosis was assessed by flow cytometry, mitochondrial membrane potential (MMP) detection and the expression of apoptosis-related proteins. Reactive oxygen species (ROS) generation was measured with 2′, 7′-dichlorofluorescein diacetate (DCFH-DA) staining. According to SAR analysis, the most potent compound 6a exhibited great inhibitory effect against A549 cells, which IC 50 value of 2.84 ± 0.68 μM. Furthermore, 6a remarkably induced DNA damage, cell cycle arrest and apoptosis in A549 cells. 6a treatment increased the levels of ROS. Network pharmacology and molecular docking predicted the potential signaling pathways and ligand-receptor interactions, and the results of western blotting showed that 6a inhibited the PI3K/Akt/Bcl-2 signaling pathway by decreasing PI3K and Bcl-2 and total level of Akt expression, while Bax and Cyt c were increasing in 6a -treated A549 cells. As mentioned above, 6a has a potent inhibitory effect in A549 cells through induction of DNA damage, apoptosis via ROS generation and modulation of PI3K/Akt/Bcl-2 signaling pathway.
研究领域:
药理学
·
肿瘤学
·
化学生物学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Membranes
·
2023
·
IF 0
Ting He,Yinchao Jin,Jie Li,Zhaoyun Sun,Zhaohui Wang,Qingguo Li,Rizhi Chen,Zhaoliang Cui,Young Moo Lee,Enrico Drioli
Extra-corporeal membrane oxygenation (ECMO) systems can perform the roles of the human heart and lungs to realize extra-corporeal oxygenation of blood. This system mainly depends on the gas-blood exchange membrane, the quality of which impacts the oxygenation performance. Currently, the most widely used gas-blood exchange membrane is made of poly(4-methyl-1-pentene) (PMP) hollow fibers. However, plasma leakage often occurs during clinical applications, which decreases the oxygenation performance and the service life and may endanger the patient's life in serious cases. In this work, Hyflon AD/PMP hollow fiber composite membranes were prepared by coating Hyflon AD on the surfaces of PMP hollow fibers to form ultra-thin, dense layers. Compared the plasma leakage time of the composite membrane with that of the pristine PMP membrane, the Hyflon AD60 layer showed great improvement in anti-leakage performance. The Hyflon AD60/PMP hollow fiber composite membrane possessed lower platelet adhesion and protein adhesion than that of the PMP membrane, indicating better blood compatibility of the Hyflon AD60 membrane. Cytotoxicity experiments were conducted to further confirm the biosafety of Hyflon AD60 as a blood contact medical membrane material. Gas permeance and oxygenation performance of the Hyflon AD60/PMP hollow fiber composite membrane were tested to ensure gas exchange efficiency during the gas separation process. Therefore, the optimized Hyflon AD60/PMP hollow fiber composite membrane has potential for clinical use.
研究领域:
生物医学工程
·
膜科学
·
体外膜肺氧合
✓ 已验证
DOI
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY
·
2010
·Vol. 48
·期 23
·5364-5374
·
IF 3.971
You-Mei Bao,Xiao-Hui Liu,Xiu-Lan Tang,Yue-Sheng Li
A series of novel hyperbranched poly(ester-amide)s (HBPEAs) based on neutral α-amino acids have been synthesized via the “AD + CBB′” couple-monomer approach. The ABB′ intermediates were stoichiometrically formed through thio-Michael addition reaction because of reactivity differences between functional groups. Without any purification, in situ self-polycondensations of the intermediates at elevated temperature in the presence of a catalyst afforded HBPEAs with multihydroxyl end groups. The degrees of branching (DBs) of the HBPEAs were estimated to be 0.40–0.58 and 0.24–0.54 by quantitative 13 C NMR with two different calculation methods, respectively, depending on polymerization conditions and structure of monomers. The influences of catalyst, temperature, and intermediate structure on the polymerization process and molecular weights as well as properties of the resultant polymers were investigated. FTIR, NMR, and DEPT-135 NMR analyses revealed the branched structure of the resultant polymers. The HBPEAs possess moderately high molecular weights with broad distributions, glass transition temperatures in the range of −25.5 to 36.5 °C, and decomposition temperatures at 10% weight loss under nitrogen and air in the regions of 243.4–289.1 °C and 231.4–265.6 °C, respectively. Among them, those derived from D , L -phenylalanine display the lowest degree of branching, whereas the highest glass transition temperature and the best thermal stability. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010
研究领域:
高分子化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2021
·
IF 3.196
Meng Ding,Lei Xu,Yumeng Zhang,Wei Li,Yuqing Zhao
20( R )-25-methoxyl-dammarane-3 β ,12 β ,20-triol (CN Patent: 201,010,107,476.7, AD-1) is a promising antitumor compound, was isolated from total hydrolyzed saponins extracted from Panax notoginseng leaves. A sensitive and rapid method for the simultaneous detection of AD-1 and its 8 major metabolites in rat feces was developed in this study. AD-1 (20 mg/kg) was orally administered to male rats by gastric intubation. Then, the feces samples were collected. After addition of internal standard (Mifepristone), feces samples were pretreated by protein precipitation followed by liquid-liquid extraction. Chromatographic separation was performed on an Angela C 18 column with gradient elution using a mobile phase composed of acetonitrile and water (containing 5 mM ammonium acetate) at a flow rate of 0.3 mL/min. The analytes were detected without any interference from the multiple reaction monitoring (MRM) mode using positive electrospray ionization. Calibration curves offered satisfactory linearity ( r > 0.995) within the determined ranges. Both intra-day and inter-day variances were lower than 15%, and the accuracy was within 85–115%. The fecal excretion recoveries of AD-1 (M0), metabolite 1 (M1), M2, M3, M4, M5, M6, M7 and M8 were 41.36%, 0.62%, 6.20%, 0.50%, 6.99%, 2.07%, 1.86%, 0.41% and 0.29%, respectively. The observed excretion profiles for AD-1 and its metabolites after oral administration are helpful to understand the poor oral bioavailability of AD-1, and will aid further investigations of AD-1 as a pharmacologically active component. Moreover, the in silico ADME (Absorption, Distribution, Metabolism, Excretion) predictions indicated that the metabolites were nontoxic and present passive gastrointestinal absorption. In previous studies, we found that M5, a metabolite of AD-1, has strong cytotoxicity against ovarian cancer cells. Further molecular docking studies showed that the most potent metabolite, M5, effectively binds to poly ADP-ribose polymerase-1 (PARP-1), which may provide novel solutions for treating ovarian cancer.
研究领域:
药理学
·
药物代谢动力学
·
计算生物学
✓ 已验证
产品关联
DOI
高影响因子
NEUROENDOCRINOLOGY LETTERS
·
2023
·Vol. 44
·期 4
·193-198
·
IF 0.7
Cheng X,Ding M,Wei C,Xiao F,Liao J,Li M,Xiao Z,Liu X,Luo Y
Objective Research has shown that hydrogen sulfide (H2S) plays a protective role in many diseases of the nervous system. The aim of this study is to investigate the effect of hypoxia on endogenous H2S concentration in the cerebral cortex of Alzheimer's disease (AD) transgenic mice and its mechanism. Methods AD transgenic mice were raised in closed boxes and pure nitrogen was introduced to reduce the oxygen concentration to 8%-10%, establishing an animal model of hypoxia. Oxygen partial pressure was measured with an oxygen meter. The expression of cystathionine-β-synthase (CBS) in cerebral cortex tissue was determined by Western blot, and H2S concentration was measured by a modified methylene blue method. Results (1) Hypoxia down-regulated CBS expression in cerebral cortex tissue of AD transgenic mice (p < 0.05). (2) The concentration of H2S in the cerebral cortex tissue of the hypoxic transgenic group was significantly lower than that of the Control group (p < 0.01). (3) Overexpression of CBS reversed the hypoxia-induced decrease of H2S concentration in the cerebral cortex tissue of AD transgenic mice (p < 0.01). Conclusions Hypoxia decreased the concentration of endogenous H2S in the cerebral cortex tissue of AD transgenic mice by down-regulating the expression of CBS.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
POLYMER
·
2011
·
IF 3.829
Youmei Bao,Jing He,Yuesheng Li
A series of novel hydroxyl- or methyl ester- terminated hyperbranched poly(ester-amide)s (HBPEAs) based on acidic ( l -glumatic acid and l -aspartic acid) and basic amino acids ( l -lysine) have been synthesized via the “AD + CBB′” couple-monomer approach. The ABB′ intermediates were stoichiometrically formed through thio-ene reaction benefited from reactivity differences between functional groups. Without any purification, in situ self-polycondensations of the intermediates at elevated temperature in the presence of Ti(OBu) 4 , as a catalyst, afforded HBPEAs with high molecular weights . More rapid polymerization rate and much higher molecular weight as well as broader polydispersity were observed for the polymerization process of intermediates based on acidic amino acids than basic amino acids which is related to the catalytic mechanism and structure difference of intermediates. Moreover, polymerization of intermediate derived from l -aspartic acid was carried out faster by comparison with that from l -glumatic acid. The DB values were approximately estimated to be 47%–49% for the polymers derived from l -aspartic acid and l -glutamic acid. The resultant HBPEAs possessed glass transition temperature ( T g ) in the range of −3 to 11 °C, among which those derived from l -lysine shows the highest T g , and decomposition temperatures at 10% weight loss under air and nitrogen are in close regions of 261–271 °C and 264–268 °C, respectively.
研究领域:
高分子化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2025
·
IF 8.2
Shuhan Wang,Yaqi Yang,Jiahong Lin,Weishan Zhang,Cuizhu Yang,Runheng Zhang,Chang Zhou,Li Zhang,Xin Wang,Jing Liu,Xiaobao Jin,Yuxin Ma
Alzheimer's disease (AD) as a common neurodegenerative disease, which characterized by amyloid Aβ deposition and neurofibrillary tangles. Astragalin (AST), a natural flavonoid, has anti-inflammatory, antioxidant, anti-cancer, and other pharmacological effects. Astrocytes can phagocytize and degrade Aβ in their vicinity. In this study, we used the AD mice model established by injecting the mixture of Aβ1-42 and Aβ25-35 into the CA1 region of the hippocampus, and C8D1A cells injured by Aβ1-42 to explore the neuroprotective effects of AST. Our findings showed that AST enhances learning and cognitive ability of AD mice, reduces Aβ deposition and neurofibrillary tangles in the brain, and improves the structural morphology of hippocampal nerve cells. Furthermore, AST promoted autophagy and suppressed apoptosis of astrocytes in the AD model. Additionally, AST inhibited the expression of proteins associated with the Fas/Fasl-VDAC1 signaling pathway, while autophagy inhibitor chloroquine (CQ) or apoptosis agonist phenoxodiol reversed above change. Interestingly, consistent with the action of pathway Fas inhibitor KR-33493, AST could activate autophagy of Aβ1-42 injured C8D1A cells while inhibit their apoptosis. In conclusion, AST activated autophagy and inhibited apoptosis of hippocampal astrocytes in AD mice, ameliorating animal cognitive deficits by down-regulating Fas/Fasl-VDAC1 signaling pathway. Thus, this study provided a new perspective and experimental foundation for developing AD treatment drugs.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Environmental Science-Nano
·
2023
·Vol. 10
·期 4
·1016-1029
·
IF 7.3
Kunyan Guo,Xile Deng,Yajun Peng,Ni Yang,Kun Qian,Lianyang Bai
Pretilachlor (Pre) is an efficient and broad-spectrum pre-seedling herbicide; however, the excessive use of the Pre traditional formulation causes phytotoxicity to rice seedlings (Oryza sativa), toxicity to soil organisms, and great environmental pollution. 4-(Dichloroacetyl)-1-oxa-4-azospiro[4,5]decane (AD-67) is a herbicide safener and it can reduce the phytotoxicity of herbicides to plants, but it degrades slowly in the aquatic environment, and extensive application leads to a wide range of negative environmental impacts. To reduce the frequency of application and increase the safety of non-target organisms, for the first time, an herbicide-safener nano-double controlled release system AD-67@Pre@ZIF-67 was successfully constructed. Pre was encapsulated in ZIF-67, metal–organic framework (MOF), and the safener AD-67 was adsorbed by self-assembly on the surface of the MOF. The release rates of Pre and AD-67 increased with the decrease in the pH value. With the lowest pH value (5.8), Pre and AD-67 were released 57% and 78% rapidly in the first 2 h, respectively, then were slowly released, and the overall releases were 86% and 96% on the 7th day, respectively. Hence, the safener AD-67 can be released quickly to protect the rice seedlings from injury caused by Pre, while Pre can release slowly from nano-double controlled release for a longer duration and show lower phytotoxicity to rice. Compared to the pre-treatment, the relative root length, relative plant height, and relative fresh weight values of rice seedlings treated with AD-67@Pre@ZIF-67 were increased by 50%, 40%, and 62%, respectively. AD-67@Pre@ZIF-67 also had lower acute toxicity to earthworms (Eisenia foetida), with the 24 h and 48 h LC50 values, which were 6 times and 5 times than that of Pre, respectively. The results showed that AD-67@Pre@ZIF-67 did not only improve the herbicidal activity to target weed barnyard grass (Echinochloa crusgalli) but also met the requirements of minimizing the adverse effects of herbicides on crop plants and environments. This shows the great application prospects in modern agriculture.
研究领域:
农业科学
·
环境科学
·
纳米技术
·
植物科学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Physical Chemistry Letters
·
2025
·
IF 4.6
Xiaohui Xu,Yu Cheng,Xinnan Xu,Weidong Tang,SiSi Liu,Chunlin Mu,Yinshi Huang,Baocong Guo,Chenglin Yan,Tao Qian
Ammonia is a hydrogen-dense, carbon-neutral energy carrier, but sluggish oxidation kinetics and catalyst toxicity limit its large-scale use in low-temperature alkaline direct ammonia fuel cells (DAFCs). Inspired by the “Grotthuss hopping” theory, we designed a hydroxyl group-modified membrane electrode catalyst system through the modification of interface key groups. This system can interact with adsorbed OH– (hereafter, OH–ad), thus being similar to a “relay” that allows OH–ad to jump from one active site to another and then react with ammonia intermediates, injecting more impetus into the kinetic process of the orderly release of OH–ad. The results of molecular dynamics (MD) simulations and operando Fourier transform infrared spectroscopy (operando-FTIR) further demonstrated and confirmed that this process follows the Gerischer–Mauerer (G–M) mechanism. Consequently, the mass activity of the best membrane electrode catalyst in this series, PtNiNC@OH0.05 (373 A g–1Pt), has been significantly enhanced in alkaline media, which is 3.2 times higher than that of the commercial 20% Pt/C (116 A g–1Pt) catalyst. Even more surprisingly, the DAFC of the membrane electrode catalyst as an anode achieves a peak power density of 17.4 mW cm–2 at 60 °C, which is 9.89-fold higher than that of 20% Pt/C (1.76 mW cm–2). The interface modification method based on the “relay” jumps proposed by us provides a way to fabricate DAFC membrane electrode catalysts.
研究领域:
能源材料
·
电化学
·
催化
·
燃料电池
·
表面化学
·
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
·
2013
·
IF 3.848
Lin-Hui Zhang,Yong-Liang Jia,Xi-Xi Lin,Hong-Quan Zhang,Xin-Wei Dong,Jun-Ming Zhao,Jian Shen,Hui-Juan Shen,Fen-fen Li,Xiao-Feng Yan,Wei Li,Yu-Qing Zhao,Qiang-Min Xie
Background Ginseng is a traditional Chinese herb that has been used for thousands of years. In the present study, effects and mechanisms of AD-1 were evaluated for its development as a novel anti-lung cancer drug. Methods The cytotoxic activity was evaluated by MTT assay. Flow cytometry was employed to detect cell cycle, apoptosis and ROS. Western blot and immunohistochemistry were used to analyze signaling pathways. Lung cancer xenograft models were established by subcutaneous implantation of A549 or H292 cells into nude mice. Results AD-1 concentration-dependently reduces lung cancer cell viability without affecting normal human lung epithelial cell viability. In A549 and H292 lung cancer cells, AD-1 induces G 0 /G 1 cell cycle arrest, apoptosis and ROS production. The apoptosis can be attenuated by a ROS scavenger — N-acetylcysteine (NAC). In addition, AD-1 up-regulates the expression of p38 and ERK phosphorylation. Addition of a p38 inhibitor SB203580, suppresses the AD-1-induced decrease in cell viability. Furthermore, genetic silencing of p38 attenuates the expression of p38 and decreases the AD-1-induced apoptosis. Treatment with NAC reduces AD-1-induced p38 phosphorylation, which indicates that ROS generation is involved in the AD-1-induced p38 activation. In mice, oral administration of AD-1 (10–40 mg/kg) dose-dependently inhibited the growth of xenograft tumors without affecting body weight and decreases the expression of VEGF, MMP-9 and CD34 in tumor tissue. TUNEL staining confirms that the tumors from AD-1 treated mice exhibit a markedly higher apoptotic index. Conclusions and general significance These data support development of AD-1 as a potential agent for lung cancer therapy.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2022
·
IF 7.31
Debo Gao,Pingli Li,Fei Gao,Yangjun Feng,Xiaolin Li,Delong Li,Yuqin Li,Yuliang Xiao
Previous studies have demonstrated that both CS and LiCl possess anti-Alzheimer's disease (AD) activities. We prepared chondroitin sulfate-Li (CS-Li) and investigated its effect on AD and explored the possible mechanisms both in vitro and in vivo . We found that CS-Li could inhibit amyloid β (A β ) aggregation and protect SH-SY5Y cells from A β 1-42 -induced cytotoxicity in vitro . In D-gal and AlCl 3 -induced AD mouse model, CS-Li improves the spatial learning and memory abilities of AD mice, reverses the nuclear pyknosis and cell edema, and increases the survival rate of neurons in hippocampus of mice. Moreover, CS-Li significantly increased the levels of GSH-Px, Na + /K + -ATPase, and ChAT and decreased the levels of MDA and AchE in AD mice. Western blot results demonstrated that CS-Li could decrease the hyperphosphorylation of tau (Ser396/Ser404) by regulating the expression of p-GSK-3 β (Ser9) and PP2A and inhibit the expression of proinflammatory factors through inhibiting NF- κ B nuclear translocation by activating the MAPK signaling pathways. In a word, CS-Li can delay AD development through multitarget processes, including A β aggregation inhibition, oxidative stress damage, tau hyperphosphorylation, and inflammatory response, thereby improves learning and memory abilities.
研究领域:
神经科学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Annals of Dermatology
·
2024
·
IF 1.5
Lin-Xia Liu,Zhi-Kai Liao,Bing-Qi Dong,Shan Jiang,Tie-Chi Lei
Background Although reports suggest that tranexamic acid (TXA) has clinical benefits for melasma patients by oral, intralesional and topical treatment, the optimal route of TXA therapy and the underlying mechanism involved remain poorly defined. Objective To compare the skin lightening effect between oral TXA and topical TXA and to dissect the molecular mechanisms using ultraviolet B (UVB)-induced hyperpigmentation mouse model, ex vivo cultured human skin explant, and cultured melanocytes (MCs) and endothelial cells. Methods Melanin content and cluster of differentiation 31 (CD31)-positive cell numbers were measured in tail skins from UVB-irradiated mice treated by intragastral or topical TXA using immunofluorescent and Fontana-Masson staining. The conditioned medium (CM) was harvested from human umbilical vein endothelial cells treated with or without 3 mM TXA and was used to treat MCs for 48 hours. mRNA and protein levels of tyrosinase and microphthalmia-associated transcription factor were measured using quantitative real-time reverse transcription polymerase chain reaction and western blotting assays. HMB45- and CD31-positive cell numbers as well as melanin content were also examined in ex vivo cultured human skin explants. Results The hyperpigmented phenotype were significantly mitigated in UVB-irradiated tail skin plus intragastral TXA-treated mice compared with mice treated with UVB only or with UVB plus topical TXA. CD31-positive cell numbers correlated with the anti-melanogenic activity of TXA therapy. The data from cultured cells and skin tissues showed that suppression of endothelin-1 (ET-1) in vascular endothelial cells by TXA reduced melanogenesis and MC proliferation. Conclusion Oral TXA outperforms topical TXA treatment in skin lightening, which contributes to suppression of ET-1 in dermal microvascular endothelial cells by TXA.
研究领域:
皮肤病学
·
分子生物学
·
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）