Latest ArticlesCircular RNA (circRNA) is a non-coding closed-loop single-stranded RNA molecule lacking the 5' end cap and the 3' poly (A) tail. Circular RNA is more abundant and stable than linear mRNA, and its expression is more conservative and specific. circRNA regulates cancer development through a variety of mechanisms, including miRNA sponges, regulating gene transcription, regulating RNA-binding proteins, and protein translation. This review summarizes the role of circRNA in cancer and helps to develop new clinical diagnostic techniques and treatments.
Chinese medicines (CM)-induced liver injury is one of the severe adverse drug reactions (ADRs) in clinical application, which restricts new drug research and development (R&D), clinical safe usage and industry development of CM. The issue, to elucidate the causality between liver injury and CM, is either a globally challenging problem or the precondition of CM safety evaluation. However, owing to the complexicity of CM and various influencing factors to CM-induced liver injury, the causality assessment for CM is much difficult, compared to synthetic drugs. Besides, the current assessment methods, primarily designed for clinical diagnosis, are difficult to be used in new drug R&D of CM. Hereinto, we reviewed the current ADR causality methods and proposed a new strategy called integrated evidence chain-based causality assessment method for CM-induced liver injury. The new causality method is designed for new drug R&D based on the complexicity of CM, to provide methodology in scientific assessment of causality of CM-induced liver injury and to promote success rate of new drug R&D. The new method could also raise our ability to find, avoid and prevent the risk of CM-induced liver injury.
Metabolomics data contains multiple variables usually processed and evaluated by means of principal components analysis. The statistical analysis of the multivariate data is involved in abstract, elusory fitting for the model of hyperspace, complicated theoretical arithmetic and sophisticated transformation of the data matrix. It is crucially important to understand the arithmetic mechanism and the properties of the models fully. In this article, we reviewed the key and puzzling issues in principal components analysis of the metabolomics data, including the principal components, the scores and loadings of a principal components, scaling and weighting, partial least square projection to latent structures, partial least squares discriminant analysis, orthogonal projection to latent structure, orthogonal bidirectional projections to latent structures, S-plot, shared and unique structure plot, and the validation of the model. Hopefully, this article provides a better understanding of data processing mode, model selection, procedure standardization, and data interpretation for a reliable conclusion.
In this study, azvudine (FNC), hydrochloride salt of azvudine (FNC-HCl) and triphosphate azovudine (FNC-TP) were tested against DENV-Ⅱ recombinant virus (DENV-Ⅱ Luc+). The inhibitory activity of FNC, FNC-HCl and FNC-TP on DENVs were detected by plaque assay. The effect on the expression of DENV-Ⅱ envelope protein E was detected by Western blot; the inhibitory of DENV-Ⅱ viral RNA by compounds was detected by real-time quantitative PCR. MTT assay was used to determine the cytotoxicity of the three compounds on Vero cells. The results showed that FNC, FNC-HCl and FNC-TP inhibited the viral replication by inhibition of renilla luciferase activity of DENV-Ⅱ Luc+. The 50% effective concentration (EC50) of FNC, FNC-HCl and FNC-TP in the inhibition of DENVs replication were from 0.54-25.42 μmol·L-1, while that of ribavirin was 40.78 ±1.02 μmol·L-1 as the positive control. Western blot and real time quantitative PCR results showed that FNC, FNC-HCl and FNC-TP significantly inhibited the expression of DENV-Ⅱ E protein, and the replication of DENV-Ⅱ viral RNA. The 50% cytotoxic concentrations of FNC, FNC-HCl and FNC-TP were all greater than 3 000.00 μmol·L-1. The results suggest that in vitro anti-DENVs activities of FNC, FNC-HCl and FNC-TP are superior to ribavirin, which are expected to become new candidates of anti-DENV drugs.
Sansanmycins (SSs), produced by Streptomyces sp. SS, belong to uridyl peptide antibiotics which exhibit a good inhibitory effect on Mycobacterium tuberculosis and Pseudomonas aeruginosa. They share a unique chemical scaffold with a 4', 5'-enamide-3'-deoxyuridine attached to DABA (N-methyl-2, 3-diaminobutyryl) which was located in the peptide chain through peptide bond. In order to study the function of related genes and to employ synthetic biology to gain new SS derivatives, we obtained a complete SS biosynthetic gene cluster and heterologously expressed it in Streptomyces coelicolor M1146, M1152 and M1154. Fermentation broth of the recombinant strains were detected using HPLC and HPLC-MS/MS, and the result showed that SS-A was successfully produced in the three strains, and its production level in S. coelicolor M1154 was similar to the original wild type strain. In addition, a potential SS analogue named as SS-1154 was discovered from the fermentation broth of S. coelicolor M1154.
Aquaporin 1 (AQP1), the first water channel protein discovered among the aquaporin family, is a hydrophobic transmembrane protein involved in transcellular water movement. Recent evidence shows that AQP1 plays a role in tumor cell proliferation and migration, angiogenesis and tumor development and progression, representing a potential therapeutic target. In this review, we discuss the structures, functions and inhibitors of AQP1, as well as the involvement of AQP1 in tumor development and progression.
Transient receptor potential vanilloid member 3 (TRPV3) is a temperature-sensitive cation channel protein, which contributes to nociception, itch, hair growth, emotional control and the pathophysiology of migraine. However, research progress on TRPV3 fundamental molecular biology is rather slow, compared to other TRP channels due to the lack of its selective antagonists. It's necessary to identify TRPV3 selective antagonists for the study on TRPV3 physiological functions. In this study, several selective TRPV3 antagonists were identified by ligand-based virtual screening of shape-based similarity and electrostatic matching. The most potent one (V-39) blocked 2-APB-activated currents in a stable human TRPV3 expressed HEK293T cell line with IC50=18.0 ±1.1 μmol·L-1 (n=4). Besides, the interaction pattern between TRPV3 and its antagonists were studied through docking the antagonists into a homology model (TRPV3_HM4) generated from the crystal structure of TPRV1. The docking results show that the binding site of TRPV3 locates between linker domain (of N-terminus and TM1) and TRP Box. There are a π-π stacking interaction and hydrogen bonding interactions between compound V-39 and residues His-310, His-314 and Arg-577 of the pocket. Identification of these antagonists provides new probes for understanding the pharmacological function of TRPV3 channel.
This study was designed to investigate the role of CD36 in palmitic acid (PA)-induced apoptosis of astrocytes and the potential mechanisms of the action. MTT assay was used to detect cell viability and TUNEL assay to detect cell apoptosis. It was found that PA significantly decreased astrocyte cell viability and increased cell apoptosis. The uptake of BODIPY FL C16 by astrocytes was measured by flow cytometry. The results showed that CD36 played a key role in the process of PA uptake by astrocytes. The changes of intracellular calcium concentration were detected by FLIPR real-time fluorescence recording system. It was found that IP3R mediated PA signal to induce intracellular calcium release and finally caused endoplasmic reticulum calcium depletion. The intracellular ROS level was detected with CM-H2DCFDA fluorescence staining. The ROS level was induced by PA in astrocytes. The effect was blocked by CD36 inhibitor SSO through inhibition of the uptake of PA. PA-induced calcium overload and ROS increase were prevented by IP3R inhibitor APB. SSO, APB and antioxidant NAC all had significant inhibitory effects on PA-induced astrocyte cell viability decrease. In conclusion, CD36 mediates the translocation of PA into astrocytes, which leads to calcium overload, oxidative stress and eventually cell apoptosis.
Poly(ADP-ribose) polymerase (PARP)-1 and PARP2 function as ADP-ribosylases involved in DNA repair. PARP1/2 is highly expressed in cancers and emerged as an attractive target for antitumor drug. In this study, we investigated the antitumor activity of a novel PARP1/2 inhibitor YHP-743 in vitro and in vivo. The results showed that YHP-743 had potent enzymatic inhibitory activity against PARP1 and PARP2 to down-regulate the PAR level. YHP-743 not only inhibited breast cancer cells with genes deficiency of homologous recombination repair, but also potentiated chemotherapy agent's cytotoxicity, such as temozolomide, topotecan, cisplatin and doxorubicin. YHP-743 elicited good antitumor activity in combination with temo-zolomide in vivo.
To compare static and dynamic metabolomics data analysis of CUMS (chronic unpredictable mild stress)-induced depression, GC-MS spectrometry was conducted on the plasma metabolome. S-Plot and ANOVA (analysis of variance)-simultaneous component analysis (ASCA) were respectively applied to static and dynamic analysis of metabolomics data. Static metabolomics data analysis revealed three typical plasma metabolites including propionic acid, D-allose, and 9, 12, 15-octadecatrienoic acid, while dynamic me-tabolomics data analysis found seven typical metabolites including propionic acid, D-allose, My-inositol, me-thylamine, etc. The abundances of typical metabolites observed by dynamic metabolomics data analysis were consistent with the variation trends of body weight and sugar water preference rate of CUMS rats. In conclusion, dynamic metabolomics analysis revealed more typical plasma metabolites, which have the potential to explain variations of body weight and behavior parameter of CUMS-induced depression rats. Combination of static and dynamic metabolomics data analysis may provide a strong support to the pathological study of complex diseases.
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62199257
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
