Latest ArticlesMetabolomics 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.
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.
Circular 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.
The chemical constituents of the fruits of Chaenomeles sinensis (Thouin) Koehne were investigated using chromatographic methods, including Diaion HP-20, Toyopearl HW-40, MCI Gel CHP-20, ODS, Silica gel chromatography and semi-preparative-HPLC. Three compounds were isolated and their structures were elucidated with spectral data and physicochemical properties, which were identified as chaenomeles alkaloid A (1), ginsenine (2) and 1, 2, 3, 4-tetrahydro-1-methyl-β-carboline-3-car-boxylic acid (3). Among those, compound 1 is a new alkaloid, compound 2 and 3 were isolated from this plant for the first time. To investigate the protective effect of compounds 1-3 on Rat adrenal pheochromocytoma (PC-12) injury induced by the β-amyloid protein (Aβ25-35). The results show that compounds 2 and 3 have a significant protective effect on the PC12 cells exposed to Aβ25-35.
Ginsenoside Rg1 is a common component of a variety of stroke and diabetes medications, but its anti-stroke effect in diabetic patients is unclear. The aim of this research is to test the therapeutic effect of Rg1 on ischemic stroke in diabetic rats, and elucidate the effect of Rg1 on post-stroke neuro-inflammation. Rg1 significantly reduced the infarct area percent, increased the behavioral score, and reduced the brain water content in diabetic rats after stroke in the diabetic rats. Rg1 reduced the post-stroke inflammatory response and decreased the expression of high mobility group box1 (HMGB1) protein significantly. Elevated level of HMGB1 activity by supplementing exogenous HMGB1 protein abolished the anti-stroke effect of Rg1, which suggests that HMGB1 is involved into the anti-stroke effect of Rg1 in the diabetic rats.
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.
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.
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.
The metabolites produced by complex and diverse microorganisms are important resources for drug research and development. Using new targets to screen microbial metabolites, many anti-cancer drugs acting on different targets are discovered. Anti-tumor antibiotics acting on various targets and signaling pathways are important members in the study of specific targets for anti-tumor, and some anticancer antibiotics with potent antitumor activity are used as "warheads" of antibody-drug conjugates. Microbial-derived anti-tumor substances acting on different targets with high-efficiency "warheads" molecules are reviewed to provide a literature basis for research on the anti-cancer drugs for specific targets derived from microorganisms.
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