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131.
The study on the mechanism and kinetics of mRNA degradation provides a new vision for chemical intervention on protein expression. The AU enrichment element (ARE) in mRNA 3′-UTR can be recognized and bound by the ARE binding protein (AU-rich Element factor (AUF1) to recruit RNase for degradation. In the present study, we proposed a novel strategy for expression regulation that interferes with the AUF1-RNA binding. A small-molecule compound, JNJ-7706621, was found to bind AUF1 protein and inhibit mRNA degradation by screening the commercial compound library. We discovered that JNJ-7706621 could inhibit the expression of AUF1 targeted gene IL8, an essential pro-inflammatory factor, by interfering with the mRNA homeostatic state. These studies provide innovative drug design strategies to regulate mRNA homeostasis. 相似文献
132.
Dominika Kajszczak Agnieszka Kowalska-Baron Dorota Sosnowska Anna Podsdek 《Molecules (Basel, Switzerland)》2022,27(10)
One of the effective treatments for diabetes is to reduce and delay the absorption of glucose by inhibition of α-amylase and α-glucosidase in the digestive tract. Currently, there is a great interest in natural inhibitors from various part of plants. In the present study, the phenolic compounds composition of V. opulus bark and flower, and their inhibitory effects on in vitro potato starch digestion as well as on α-amylase and α-glucosidase, have been studied. Bark and flower phenolic extracts reduced the amount of glucose released from potato starch during tree-stage simulated digestion, with IC50 value equal to 87.77 µg/mL and 148.87 µg/mL, respectively. Phenolic bark extract showed 34.9% and 38.4% more potent inhibitory activity against α-amylase and α-glucosidase, respectively, but the activity of plant extracts was lower than that of acarbose. Chlorogenic acid (27.26% of total phenolics) and (+)-catechin (30.48% of total phenolics) were the most prominent phenolics in the flower and bark extracts, respectively. Procyanidins may be responsible for the strongest V. opulus bark inhibitory activity against α-amylase, while (+)-catechin relative to α-glucosidase. This preliminary study provides the basis of further examination of the suitability of V. opulus bark compounds as components of nutraceuticals and functional foods with antidiabetic activity. 相似文献
133.
Baiji Xue Yanhua Yu Guoqiang Peng Mengmeng Sun Peng Lv Xuefeng Li 《Molecules (Basel, Switzerland)》2022,27(10)
Amphotericin B (AMB) is an antifungal drug used for serious fungal infections. However, AMB has adverse reactions such as nephrotoxicity, which limit the clinical application of AMB alone or in combination with other antifungal drugs. Nano or micro drug delivery systems (DDS) have been proven to be effective in reducing the toxic and side effects of drugs. Further, the combination of AMB with other compounds with antifungal activity, such as curcumin (CM), may enhance the synergistic effects. Herein, AMB and CM were co-loaded into porous poly (lactic-co-glycolic acid) (PLGA) microparticles (MPs) to prepare AMB/CM-PLGA MPs. The AMB/CM-PLGA MPs showed a remarkably reduced hemolysis (62.2 ± 0.6%) compared to AMB (80.9 ± 1.1%). The nephrotoxicity of AMB/CM-PLGA MPs is significantly lower than that of AMB. In vitro, AMB/CM-PLGA MPs had better inhibitory effects on the adhesion and biofilm formation of Candida albicans compared with AMB. Experiments on mice infected with C. albicans showed that AMB/CM-PLGA MPs have a better therapeutic effect than AMB in vivo. In summary, AMB/CM-PLGA MPs may be a novel and promising therapeutic candidate for fungal infection. 相似文献
134.
Marcin Feldo Magdalena Wjciak Aleksandra Ziemlewska Sawomir Dresler Ireneusz Sowa 《Molecules (Basel, Switzerland)》2022,27(13)
Diosmin is widely used as a venoactive drug in the pharmacological treatment of chronic venous disorders. It exerts a strong protective effect on blood vessels via an increase in the elasticity of vessel walls and reduces the permeability of capillary walls, thereby producing an anti-edematous effect. In this paper, we investigated the effectiveness of diosmin and diosmetin in modulating the level of proinflammatory factors in human skin fibroblasts treated with lipopolysaccharide (LPS). Two variants of the experiments were performed: the flavonoid was added 2 h prior to or 24 h after LPS stimulation. Our study revealed that both flavonoids reduced the levels of IL-6 and Il-1β as well as COX-2 and PGE2 but had no impact on IL-10. However, the addition of the compounds prior to the LPS addition was more effective. Moreover, diosmetin modulated the proinflammatory factors more strongly than diosmin. Our investigations also showed that both flavonoids were potent inhibitors of elastase and collagenase activity, and no differences between the glycoside and aglycone forms were observed. 相似文献
135.
Katarzyna Sujka Grayna Cacak-Pietrzak Alicja Suek Karolina Murgrabia Dariusz Dziki 《Molecules (Basel, Switzerland)》2022,27(13)
This work aimed to evaluate the effect of partial replacement of semolina with 0, 1, 5, 10, 15, and 20% of ground buckwheat hull (BH) on the chemical composition, antioxidant properties, color, cooking characteristics, and sensory properties of wheat pasta. Pasta samples were prepared by dough lamination (tagliatelle shape) and dried at 55 °C until the moisture content was 11–12% (wet basis). Analyses of samples showed that the addition of BH caused an increase in fiber content in pasta from 4.31% (control pasta) to 14.15% (pasta with 20% of BH). Moreover, the brightness and yellowness of BH-enriched products were significantly decreased compared to the control sample, and the total color difference ranged from 23.84 (pasta with 1% of BH) to 32.56 (pasta with 15% BH). In addition, a decrease in optimal cooking time, as well as an increased weight index and cooking loss, was observed in BH-enriched pasta samples. Furthermore, BH-enriched cooked pasta had significantly higher total phenolic content and antioxidant activity but an unpleasant smell and taste, especially if the level of BH was higher than 10%. 相似文献
136.
Zelong Gong Xuefeng Gao Qingqing Yang Jingxian Lun Hansen Xiao Jiayu Zhong Hong Cao 《Molecules (Basel, Switzerland)》2022,27(13)
Enterovirus 71 (EV71) is a dominant pathogenic agent that may cause severe central nervous system (CNS) diseases among infants and young children in the Asia-pacific. The inflammasome is closely implicated in EV71-induced CNS injuries through a series of signaling pathways. However, the activation pathway of NLRP3 inflammasome involved in EV71-mediated CNS injuries remains poorly defined. In the studies, EV71 infection, ERK1/2 phosphorylation, and activation of NLRP3 are abolished in glioblastoma cells with low vimentin expression by CRISPR/Cas9-mediated knockdown. PD098059, an inhibitor of p-ERK, remarkably blocks the vimentin-mediated ERK1/2 phosphorylation in EV71-infected cells. Nuclear translocation of NF-κB p65 is dependent on p-ERK in a time-dependent manner. Moreover, NLRP3 activation and caspase-1 production are limited in EV71-infected cells upon the caffeic acid phenethyl ester (CAPE) administration, an inhibitor of NF-κB, which contributes to the inflammasome regulation. In conclusion, these results suggest that EV71-mediated NLRP3 inflammasome could be activated via the VIM-ERK-NF-κB pathway, and the treatment of the dephosphorylation of ERK and NF-κB inhibitors is beneficial to host defense in EV71-infected CNS. 相似文献
137.
Pin Gong Yuxi Guo Xuefeng Chen Dandan Cui Mengrao Wang Wenjuan Yang Fuxin Chen 《Molecules (Basel, Switzerland)》2022,27(13)
The structural characterization, the in vitro antioxidant activity, and the hypoglycemic activity of a polysaccharide (SGP-1-1) isolated from Siraitia grosvenorii (SG) were studied in this paper. SGP-1-1, whose molecular weight is 19.037 kDa, consisted of Gal:Man:Glc in the molar ratio of 1:2.56:4.90. According to the results of methylation analysis, GC–MS, and NMR, HSQC was interpreted as a glucomannan with a backbone composed of 4)-β-D-Glcp-(1→4)-, α-D-Glcp-(1→4)-, and 4)-Manp-(1 residues. α-1,6 linked an α-D-Galp branch, and α-1,6 linked an α-D-Glcp branch. The study indirectly showed that SGP-1-1 has good in vitro hypoglycemic and antioxidant activities and that these activities may be related to the fact that the SGP-1-1’s monosaccharide composition (a higher proportion of Gal and Man) is the glycosidic-bond type (α- and β-glycosidic bonds). SGP-1-1 could be used as a potential antioxidant and hypoglycemic candidate for functional and nutritional food applications. 相似文献
138.
Shanshan Wang Xianbo Kong Zhangjing Chen Guopin Wang Juan Zhang Jing Wang 《Molecules (Basel, Switzerland)》2022,27(13)
Alzheimer’s disease (AD) is a progressive neurological condition. The rising prevalence of AD necessitates the rapid development of efficient therapy options. Despite substantial study, only a few medications are capable of delaying the disease. Several substances with pharmacological activity, derived from plants, have been shown to have positive benefits for the treatment of AD by targeting various enzymes, such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), β-secretase, γ-secretase, and monoamine oxidases (MAOs), which are discussed as potential targets. Medicinal plants have already contributed a number of lead molecules to medicine development, with many of them currently undergoing clinical trials. A variety of medicinal plants have been shown to diminish the degenerative symptoms associated with AD, either in their raw form or as isolated compounds. The aim of this review was to provide a brief summary of AD and its current therapies, followed by a discussion of the natural compounds examined as therapeutic agents and the processes underlying the positive effects, particularly the management of AD. 相似文献
139.
Gredson Keiff Souza Andr Gallo Luiza Hauser Novicki Heitor Rodrigues Neto Eneida de Paula Anita Jocelyne Marsaioli Luis Fernando Cabea 《Molecules (Basel, Switzerland)》2022,27(13)
The drugs delivery system in the treatment of diseases has advantages such as reduced toxicity, increased availability of the drug, etc. Therefore, studies of the supramolecular interactions between local anesthetics (LAs) butamben (BTB) or ropivacaine (RVC) complexed with 2-hydroxypropyl-β-cyclodextrin (HP-βCD) and carried in Stealth liposomal (SL) are performed. 1H-NMR nuclear magnetic resonance (DOSY and STD) were used as the main tools. The displacements observed in the 1H-NMR presented the complexion between LAs and HP-βCD. The diffusion coefficients of free BTB and RVC were 7.70 × 10−10 m2 s−1 and 4.07 × 10−10 m2 s−1, and in the complex with HP-βCD were 1.90 × 10−10 m2 s−1 and 3.64 × 10−10 m2 s−1, respectively, which indicate a strong interaction between the BTB molecule and HP-βCD (98.3% molar fraction and Ka = 72.279 L/mol). With STD-NMR, the encapsulation of the BTB/HP-βCD and RVC/HP-βCD in SL vesicles was proven. Beyond the saturation transfer to the LAs, there is the magnetization transfer to the hydrogens of HP-βCD. BTB and RVC have already been studied in normal liposome systems; however, little is known of their behavior in SL. 相似文献
140.
Chun-Yan Zhang Li-Jing Peng Guo-Ying Chen Hao Zhang Feng-Qing Yang 《Molecules (Basel, Switzerland)》2022,27(13)
The peroxidase-like activity of vitamin B6 (VB6) was firstly demonstrated by catalyzing the peroxidase chromogenic substrate 3,3′,5,5′-tetramethylbenzidine (TMB) at the existence of H2O2. The influence of different factors on the catalytic property of VB6, including pH, temperature, VB6 concentration, and incubation time, were investigated. The steady-state kinetic study results indicate that VB6 possesses higher affinity to H2O2 than natural horseradish peroxidase and some other peroxidase mimics. Besides, the radical quenching experiment results confirm that hydroxyl radical (•OH) accounts for the catalytic process. Based on the excellent peroxidase-like catalytic activity of VB6, the colorimetric methods for H2O2 and gallic acid (GA) detection were developed by measuring the absorbance variance of the catalytic system. Under the optimal conditions, the linear ranges of the methods for H2O2 and GA determination with good selectivity are 50.0–600.0 μM and 10.0–50.0 μM, respectively. In addition, the developed method was applied in the detection of H2O2 in milk samples and evaluation of total antioxidant capacity of different tea infusions. This study may broaden the application prospect of VB6 in environmental and biomedical analysis fields, contribute to profound insight of the physiological functions of VB6, as well as lay foundation for further excavation of small-molecule peroxidase mimics. 相似文献