Traditional Chinese medicine treatment of diseases has been recognized, but the material basis and mechanisms are not clear. In this study, target prediction of the antigastric cancer (GC) effect of ...Guiqi Baizhu (GQBZP) and the analysis of potential key compounds, key targets, and key pathways for the therapeutic effects against GC were carried out based on the method of network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment. There were 33 proteins shared between GQBZP and GC, and 131 compounds of GQBZP had a high correlation with these proteins, indicating that the PI3K‐AKT signaling pathway might play a key role in GC. From these studies, we selected human epidermal growth factor receptor 2 (HER2) and programmed cell death 1‐ligand 1 (PD‐L1) for docking; the results showed that 385 and 189 compounds had high docking scores with HER2 and PD‐L1, respectively. Six compounds were selected for microscale thermophoresis (MST). Daidzein/quercetin and isorhamnetin/formononetin had the highest binding affinity for HER2 and PD‐L1, with Kd values of 3.7 μmol/L and 490, 667, and 355 nmol/L, respectively. Molecular dynamics simulation studies based on the docking complex structures as the initial conformation yielded the binding free energy between daidzein/quercetin with HER2 and isorhamnetin/formononetin with PD‐L1, calculated by molecular mechanics Poisson‐Boltzmann surface area, of −26.55, −14.18, −19.41, and −11.86 kcal/mol, respectively, and were consistent with the MST results. In vitro experiments showed that quercetin, daidzein, and isorhamnetin had potential antiproliferative effects in MKN‐45 cells. Enzyme activity assays showed that quercetin could inhibit the activity of HER2 with an IC50 of 570.07 nmol/L. Our study provides a systematic investigation to explain the material basis and molecular mechanism of traditional Chinese medicine in treating diseases.
We are committed to establishing a systematic research method based on network pharmacology, multitarget molecular docking, molecular dynamics simulation, and protein and experimental verification in vitro and in vivo, to establish a systematic analysis method for traditional Chinese medicine (TCM) treatment of diseases. We aim to provide a possible theoretical and experimental basis for the standardization and internationalization of TCM.
Abstract Terminalia chebula exhibits a high level of antioxidant capacity and is highly valued in medicine and cosmetics. However, its main efficacy and active ingredients related to antioxidant, ...whitening, and anti‐aging are still unclear. In this study, the active site responsible for its cosmetic efficacy was specified by the biological activity‐guided method and further characterized by using ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (UHPLC‐QTOF‐MS/MS). T. chebula was ultrasonically extracted by five solvents, and 30% ethanol extract was screened out for subsequent purification by 1,1‐D‐iphenyl‐2‐picrylhydrazyl radical (DPPH), 2,2′‐Azinobis‐(3‐ethylbenzothiazoline‐6‐sulphonate) (ABTS), hydroxyl, and superoxide anion free radical scavenging assays. Five elution fractions were obtained by column chromatography on D101 macroporous adsorbent resin eluted by an increased proportion of ethanol. The 30% ethanol elution fraction was specified as the enrichment site of active ingredients showing good antioxidant capacity and potent inhibitory activity against tyrosinase and elastase. A total of 30 compounds were identified by UHPLC‐QTOF‐MS/MS in the 30% ethanol elution fraction, including 11 gallotannins, 14 ellagitannins, and 5 other compounds, and these compounds may be the key ingredients in cosmetics beneficial for the skin. Such a biological activity‐guided method has provided a simple and rapid venue for specifying the components of medicinal herbs responsible for cosmetic efficacy.
This letter demonstrates an ultra-wideband circularly polarized cavity-backed crossed-dipole antenna. It consists of a modified crossed-dipole and a modified cavity. Each arm of the modified ...crossed-dipole is mainly made up by the combination of a triangle and a fan-shaped sector, and the arms within the same layer of substrate are connected by a vacant-quarter ring. The modified cavity is composed of a rectangular cavity, four coupled rotated vertical metallic plates, and four sequentially rotated metallic steps. Through combining the modified crossed-dipole and modified cavity together, ultra-wideband characteristics in terms of - 10-dB impedance bandwidth (IBW) and 3-dB axial-ratio bandwidth (ARBW) can be realized. The IBW and ARBW are correspondingly calculated to be 128.9% and 121.2%. The prototype of the proposed antenna was fabricated and measured. The proposed antenna has a compact size of 0.74 λ
× 0.74 λ
× 0.17 λ
(λ
is the wavelength at the lowest frequency of operation band). The measured IBW and ARBW are 125.2% (1.67-7.26 GHz) and 120.1% (1.79-7.17 GHz), respectively, which are in good agreement with the simulated ones. The proposed antenna has stable radiation patterns in the operation band and exhibits a right-hand circular polarization with a peak gain of 12.2 dBic at 6.7 GHz.
Based on a variant strain, we constructed a gE/gI/TK-deleted pseudorabies virus (PRV). A total of 18 female mice were randomized to a vaccination group to receive PRV XJ delgE/gI/TK, a vehicle group ...to receive Dulbecco's modified Eagle's medium, and a mock group to confirm the protection of PRV delgE/gI/TK on the central nervous system in mice. Subsequently, the vaccination and vehicle groups were infected with PRV XJ. The mice in the vehicle group showed more severe neurological symptoms and higher viral loads than those in the vaccination group. The exudation of Evans blue and the expression of tight junction protein showed no difference in all groups. HE staining showed vacuolar neuronal degeneration in the vehicle group brain, but no tissue lesions were observed in the vaccination group. TNF-α, IL-6, and synuclein were upregulated in the brain of mice in the vehicle group, while those were inhibited among mice in the vaccination group. IFN-β, IFN-γ, ISG15, Mx1, and OAS1 showed no difference in the brain between the vaccination and vehicle groups. In addition, TNF-α and IL-6 were inhibited, and antiviral factors were increased in the intestine of the mice in the vaccination group compared to those in the vehicle group. Our study showed that PRV XJ delgE/gI/TK inhibited neurological damage and the inflammation of the intestine and brain induced by PRV and activated the innate immunity of the intestine.
Dengue used to be recognized as an imported and sporadic disease in China. Since June 2014, an unexpected large dengue outbreak has attacked Guangzhou, China, resulting in more than 40,000 cases. ...Among the 1,942 laboratory-confirmed hospitalized dengue cases, 121 were diagnosed as severe dengue according to the 2009 WHO guideline, and 2 patients finally died. Laboratory diagnosis and virus isolation demonstrated that the majority (96%) cases were caused by dengue virus serotype 1 (DENV-1), and the others by serotype 2 (DENV-2). 14 DENV strains were isolated from the sera of acute-phase dengue patients during this outbreak, and the complete envelope (E) gene of 12 DENV-1 strains and two DENV-2 strains were determined using RT-PCR assay. Phylogenetic analysis based on the E gene revealed the DENV-1 strains isolated during the outbreak belonged to genotype I and V, respectively. These isolates formed three clades. DENV-2 isolates were assigned to the same clade belonging to genotype cosmopolitan. These strains isolated in 2014 were closely related to the isolates obtained from the same province, Guangdong, in 2013. No amino acid mutations known to increase virulence were identified throughout the E protein of isolates in 2014. These results indicate that dengue is turning into endemic in Guangdong, China, and extensive seroepidemiological investigation and mosquito control measures are critically needed in the future.
miRNA expression profiles in ectopic endometrium (EC) serving as pathophysiologic genetic fingerprints contribute to determining endometriosis progression; however, the underlying molecular ...mechanisms remain unknown.
miRNA microarray analysis was used to determine the expression profiling of EC fresh tissues. qRT-PCR was performed to screen miR-205-5p expression in EC tissues. The roles of miR-205-5p and its candidate target gene, angiopoietin-2 (ANGPT2), in endometriosis progression were confirmed on the basis of both in vitro and in vivo systems. miR-205-5p and ANGPT2 expression were measured by in situ hybridization and immunochemistry, and their clinical significance was statistically analysed.
miR-205-5p was screened as a novel suppressor of endometriosis through primary ectopic endometrial stromal cell migration, invasion, and apoptosis assay in vitro, along with endometrial-like xenograft growth and apoptosis in vivo. In addition, ANGPT2 was identified as a direct target of miR-205-5p through bioinformatic target prediction and luciferase reporter assay. Re-expression and knockdown of ANGPT2 could respectively rescue and simulate the effects induced by miR-205-5p. Importantly, the miR-205-5p-ANGPT2 axis was found to activate the ERK/AKT pathway in endometriosis. Finally, miR-205-5p and ANGPT2 expression were closely correlated with the endometriosis severity.
The newly identified miR-205-5p-ANGPT2-AKT/ERK axis illustrates the molecular mechanism of endometriosis progression and may represent a novel diagnostic biomarker and therapeutic target for disease treatment.
Periodontitis and hypertension often occur as comorbidities, which need to be treated at the same time. To resolve this issue, a controlled‐release composite hydrogel approach is proposed with dual ...antibacterial and anti‐inflammatory activities as a resolution to achieve the goal of co‐treatment of comorbidities. Specifically, chitosan (CS) with inherent antibacterial properties is cross‐linked with antimicrobial peptide (AMP)‐modified polyethylene glycol (PEG) to form a dual antibacterial hydrogel (CS‐PA). Subsequently, curcumin loaded into biodegradable nanoparticles (CNP) are embedded in the hydrogel exhibiting high encapsulation efficiency and sustained release to achieve long‐term anti‐inflammatory activities. In a mouse model of periodontitis complicated with hypertension, CS‐PA/CNP is applied to gingival sulcus and produced an optimal therapeutic effect on periodontitis and hypertension simultaneously. The therapeutic mechanisms are deeply studied and indicated that CS‐PA/CNP exerted excellent immunoregulatory effects by suppressing the accumulation of lymphocytes and myeloid cells and enhanced the antioxidant capacity and thus the anti‐inflammatory capacity of macrophages through the glutathione metabolism pathway. In conclusion, CS‐PA/CNP has demonstrated its superior therapeutic effects and potential clinical translational value in the co‐treatment of periodontitis and hypertension, and also serves as a drug delivery platform to provide combinatorial therapeutic options for periodontitis with complicated pathogenesis.
CS‐PA hydrogel with dual antibacterial activities is fabricated through the thiol‐maleimide click reaction, where curcumin nanoparticles are physically incorporated. By in situ injection of the hydrogel into periodontal pockets, CS‐PA/CNP can inhibit various periodontal pathogens and restore immune hemostasis to effectively manage periodontitis, which reverses periodontitis‐exacerbated hypertension in the meantime.
Type I interferons (IFNs) are produced by almost all cell types and play a vital role in host defense against viral infection. Infection with an RNA virus activates receptors such as RIG-I, resulting ...in the recruitment of the adaptor protein MAVS to the RIG-I-like receptor (RLR) signalosome and the formation of prion-like functional aggregates of MAVS, which leads to IFN-β production. Here, we identified the aldehyde dehydrogenase 1B1 (ALDH1B1) as a previously uncharacterized IFN-stimulated gene (ISG) product with critical roles in the antiviral response. Knockout of ALDH1B1 increased, whereas overexpression of ALDH1B1 restricted, the replication of RNA viruses, such as vesicular stomatitis virus (VSV), Zika virus (ZIKV), dengue virus (DENV), and influenza A virus (IAV). We found that ALDH1B1 localized to mitochondria, where it interacted with the transmembrane domain of MAVS to promote MAVS aggregation. ALDH1B1 was recruited to MAVS aggregates. In addition, ALDH1B1 also enhanced the interaction between activated RIG-I and MAVS, thus increasing IFN-β production and the antiviral response. Furthermore,
mice developed more severe symptoms than did wild-type mice upon IAV infection. Together, these data identify an aldehyde dehydrogenase in mitochondria that functionally regulates MAVS-mediated signaling and the antiviral response.
Alzheimer's disease (AD) is a progressive and deadly neurodegenerative disease that is characterized by memory loss, cognitive impairment and dementia. Several hypotheses have been proposed for the ...pathogenesis based on the pathological changes in the brain of AD patients during the last few decades. Unfortunately, there is no effective agents/therapies to prevent or control AD at present. Currently, only a few drugs, which function as acetylcholinesterase (AChE) inhibitors or N-methyl-Daspartate (NMDA) receptor antagonists, are available to alleviate symptoms. Since many small molecule natural products have shown their functions as agonists or antagonists of receptors, as well as inhibitors of enzymes and proteins in the brain during the development of central nervous system (CNS) drugs, it is likely that natural products will play an important role in anti-AD drug development. We review recent papers on using small molecule natural products as drug candidates for the treatment of AD. These natural products possess antioxidant, anti-inflammatory, anticholinesterase, anti-amyloidogenic and neuroprotective activities. Moreover, bioactive natural products intended to be used for preventing AD, reducing the symptoms of AD and the new targets for treatment of AD are summarized.
PDF
