To prepare the mimetic exosomes and co-delivery proteins and nucleic acids, and achieve efficient and safe co-delivery of multi-component drugs, an optimized formulation was designed by modifying a polylactic acid-glycolic acid copolymer (PLGA) matrix with a cationic lipid excipient dioleyl trimethylammonium propane (DOTAP), and a PLGA/DOTAP nanoparticles packaged protein and nucleic acid was prepared by double emulsion method, and the outermost membrane structure prepared by reverse phase evaporation method and consists of 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1, 2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol and membrane proteins. The structure of the mimetic exosomes is formed by ultrasonic dispersion and extrusion, and analyzed its characteristics and nature of the transfer effect. The size of mimetic exosomes was about 156.13 nm, with negative charge (-18.23 ±0.57 mV), and it could efficiently co-transfer protein and siRNA, and siRNA could effectively inhibit the expression of target gene Trim28. The mimetic exosomes simulate the structure of exosomes and achieve safe and efficient co-delivery of multi-component drugs.

Plant polyphenols have a wide range of pharmacological activities and application prospects. Liquid polyphenol preparations have special physical phases and complex chemical compositions, with problems such as poor stability and easy precipitation during production and marketing. Taking the multi-precipitation mechanism of plant polyphenol liquid preparations as an example, we discuss the chemistry and composition of the precipitation, how it forms, whether precipitationcan be controlled, and the interaction law of three precipitation approaches. An unstable mechanism model is proposed where hydrolyzed tannin hydrolysis and catechin non-enzymatic oxidative polymerization repeatedly induces associative colloid aggregation and precipitation. This study explains the complex physicochemical changes in polyphenol solutions and the microcosmic mechanism of instability in the induced system and proposes a steady state reconstruction of liquid polyphenol preparation consistent with the common law of precipitation and control. It has scientific significance for promoting the development and manufacture of high quality liquid polyphenol preparations.

¹H NMR-based metabonomic analysis was used to elucidate the hypoglycemic mechanism of Astragalus Radix and Dioscoreae Rhizomacomes. Thirty-seven SD rats were divided into four groups:model group (M group), control group (C group), Astragalus Radix and Dioscoreae Rhizomacomes group (HS group), metformin group (Y group). A T2DM model was induced with a high fat diet and streptozotocin (STZ). Drug was continuously administered for 8 weeks, after which blood and the kidneys were collected to determine the biochemical index and the kidney coefficients of each group. Using ¹H NMR metabolomics technology, we measured the metabolites in the urine of rats in each group to identify appropriate biomarkers. The results showed that total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (L-DLC), blood urea nitrogen (BUN), hemoglobin A1c (HbA1c) and the kidney coefficients were significantly increased with high density lipoprotein (H-DLC) significantly decreased in the diabetic group, but these changes were largely reversed with treatment with Astragalus Radix and Dioscoreae Rhizomacomes. A total of 20 biomarkers were found in rat urine in the diabetic group and Astragalus Radix and Dioscoreae could reverse the changes of 16 of these metabolites to varying degrees, similar to that of metformin (200 mg·kg^-1). The changes in metabolomics mainly involved butanoate metabolism, the tricarboxylic acid (TCA) cycle, taurine and hypotaurine metabolism, synthesis and degradation of ketone bodies, and pyruvate metabolism. Dioscoreae Rhizomacomes and Astragalus Radix may have a therapeutic role in the treatment of diabetes through the above five metabolic pathways, revealing the possible therapeutic mechanisms for Dioscoreae Rhizomacomes and Astragalus Radix.

In order to explore MYB transcription factors related to developmental processes and secondary metabolism in Morinda officinalis, we analyzed MoMYB expression based on transcriptome data from three tissues (root, stem and leaf). We used this analysis to provide a theoretical foundation for regulating the metabolism of M. officinalis. RNA-seq data along with the five databases including PFAM and plantTFDB and others were used to screen and classify MoMYB, including GO functional annotation and classification, subcellular localization, signal peptide prediction, conserved motif discovery, and comparative phylogenetic analysis. RT-qPCR was carried out to detect tissue-specific expression differences of MoMYB genes. According to transcriptome data, 109 MoMYB sequences were identified and divided into four classes, containing 51 sequences related to R2R3-MYB. Subcellular localization analysis indicated that a majority of sequences were located in nucleus. Blast2GO analysis showed that 109 MoMYB sequences were classified into three major functional ontologies including molecular function (112), biological processes (76) and cellular components (239). The R2-MYB conserved motif of 51 R2R3-MYB sequences possessed three significantly conserved tryptophan residues, whereas a phenylalanine replaced the first tryptophan in R3-MYB. The results of multiple sequence alignment and phylogenetic analysis revealed that the R2R3-MYB was distributed in all subgroups, apart from the S10, S19 and S21 subgroups. RT-qPCR indicated that several R2R3-MYB genes were differentially expressed among the three tissues, and this finding was consistent with transcriptome data. The 109 MoMYB sequences were annotated and divided into different classes, which lays the foundation for further study on MYB transcriptional factors in M. officinalis.

Cardiovascular diseases (CVDs) and malignant tumors are the main causes of death worldwide. The etiology study of CVDs and malignant tumors has found a series of widely recognized risk factors. Medical practice and medical theory usually focus on one of the diseases, but more and more evidence reveals that malignant tumors usually involve the cardiovascular system, thus leading to thromboembolism, heart failure, etc. Anti-cancer treatment proves to induce CVDs, while CVDs seem to increase the risk of malignant tumors. This situation requires researchers to conduct further combined crossover study on both CVDs and malignant tumors. In this review, we discuss the potential common risk factors of cardiovascular diseases and malignant tumors, the pathological and physical mechanism of the two kinds of diseases, the cardiac toxicity induced by tumor therapy and the impact of cardiovascular drugs on cancer from the perspective of cardio-oncology, and in the endput forward the prospect of prevention and treatment.

Physiologically based pharmacokinetic (PBPK) modeling is an important tool to predict pharmacokinetic or pharmacodynamic profiles in special populations, especially in children and infants where designing and conducting clinical studies is difficult. The application of PBPK modeling can effectively promote the development of pediatric drugs and their clinical use. At present, PBPK modeling of pediatric populations is mainly applied in clinical trial design, drug-drug interaction (DDI) risk assessment, and dose selection in children. This review discusses the advantages of PBPK modeling in pediatric drug research and summarizes how to extrapolate a PBPK model from adults to children. The theoretical basis for pediatric PBPK models, the modelling process and important physiological parameters during the modeling process are introduced. Some successful applications of PBPK modeling in pediatric drug research and development are also presented. This review also analyzes the current limitations and future directions of pediatric PBPK modeling.

The senescence-associated secretory phenotype (SASP) is a generic term for the secretion of a series of cytokines such as pro-inflammatory factors, chemokines and proteases, and is a key feature of senescent cells. SASP is a double-edged sword that can resist a harmful environment in normal cells, but with the decline of body function, the massive secretion of cytokines, chemokines and proteases accelerates aging while inducing inflammation, leading to the development of various aging-related diseases. This article reviews the composition and physiological functions of SASP, the changes in SASP during aging, the regulatory pathways associated with SASP, and the anti-aging drugs that regulate SASP. This article aims to present a more comprehensive understanding of SASP and lay the foundation for SASP-based anti-aging research and the discovery of new targets for anti-SASP drugs.

The resistance and dose limitation of tumors is a serious obstacle to cytotoxic drug therapy in the field of medical oncology. Nitric oxide (NO) is a powerful adjuvant for tumor hypersensitivity for traditional chemotherapy and radiation therapy. The concentration of NO plays an important role in affecting its anti-tumor effect. This review summarizes the mechanism of concentration-dependent effects of NO on tumor cells and the mechanism of chemotherapy sensitization. It provides evidence for rational use of NO to exert anti-tumor effects, and overcoming multidrug resistance and anti-tumor drug development.

Phytochemical study of the aerial parts of Hypericum perforatum L. resulted in the isolation of an undescribed compound, which was identified as Rel-(2S, 3R)-2-(3, 4-dihydroxyphenyl)-3, 5, 7-trihydroxy-2-methoxy-3-(2-oxopropyl)chroman-4-one (1) by spectroscopic methods including UV, IR, HR-ESI-MS, 1D and 2D NMR spectra. Compound 1 is a new 2, 3-dioxo-flavone with an acetonyl moiety, rarely found in nature. In addition, a plausible biogenetic pathway of 1 was proposed in this article.

Injectable traditional Chinese medicine often contains multiple components including undefined toxic substances, can have high variability between batches, with undefined mechanisms of action. It is urgent to improve the quality and consistency and reduce the toxicity risk of traditional Chinese medicine. The Microtox technology is a simple, rapid method for the detection of toxic substances in the environment that uses non-pathogenic luminescent bacteria as an indicator, and the change in luminosity as an index. Using this bioassay we have systematically applied Microtox technology for the detection of microtoxicity in injectable traditional Chinese medicine. As a new method of bioactivity characterization, Microtox technology is expected to be used in the detection of quality fluctuations and toxicity risks at an early stage in the preparation of injectable traditional Chinese medicines and to improve the quality of injectable traditional Chinese medicine.