Brain-targeted delivery plays an important role in the diagnosis and treatment of neurological diseases, but the existence of blood brain barrier (BBB) limits the development of brain-targeted delivery. As cell-derived nanovesicles, exosomes can participate in the transportation of substances between cells to mediate the communication between cells to play a biological regulatory role in vivo. Due to the low immunogenicity, low toxicity, high engineering and natural crossing over BBB, exosomes play an important role in brain-targeted delivery. In this paper, the composition of exosomes, the mechanism of brain targeted delivery and its role in various brain diseases are systematically described.

Rehmannia glutinosa belongs to the Scrophulariaceae family with important medicinal value. In order to effectively explore the transcriptome information of R. glutinosa and identify the genes encoding enzymes involved in phenylethanol glycoside (PhGs) biosynthesis, the leaves, stems and tuberous roots of R. glutinosa were used for transcriptome sequencing using Pacific Biosiences RS Ⅱ platform. A total of 27 773 transcripts were generated with an average length of 2 380 bp, and 27 236 coding sequences (CDS) were predicted. Using BLAST software, non-redundant transcript sequences were annotated with NR, NT, GO, COG, KEGG, SwissProt and Interpro databases and a total of 27 399 annotated genes were obtained. Among them, the number of genes related to Sesamum indicum in the NR database was the highest (81.44%), which is consistent with their evolutionary relationship. Enzymes likely involved in the biosynthesis of isoacteoside, echinacoside, cistanosides A, cistanosides F, 2′-acetylacteoside and leonoside F were identified, and 143 genes were identified in R. glutinosa full-length transcriptome. The expression levels of 19 genes correlated with acteoside content in twelve tissues of R. glutinosa, and most showed higher expression levels in leaf tissues and floral organs. This study provides more reliable transcriptome data for screening R. glutinosa for functional genes and provides a foundation for the study of the molecular mechanisms of PhGs biosynthesis.

To establish a quantitative analysis of multi-components by single marker (QAMS) for the determination of Aster souliei Franch., the relative correction factors (f_x) of neochlorogenic acid, cryptochlorogenic acid, rutin, isoquercitrin, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, quercetin, apigenin and kaempferol were established by ultra-high performance liquid chromatography with chlorogenic acid as internal reference. Meanwhile, the content of each component was determined by the external standard method (ESM) and QAMS, and a linear regression model was established to verify the feasibility and accuracy of the QAMS. Hierarchical clustering analysis (HCA) and orthogonal partial least square discriminate analysis (OPLS-DA) were used to evaluate the quality of 23 batches of A. souliei. The results showed that the repeatability of each f_x was good. The average content of neochlorogenic acid, cryptochlorogenic acid, rutin, isoquercitrin, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, quercetin, apigenin and kaempferol in 23 batches of A. souliei by QAMS was 0.165, 0.234, 6.115, 0.478, 0.484, 3.359, 1.382, 0.210, 0.172, and 0.057 mg·g^-1, respectively. The mean content determined by the ESM method was 0.163, 0.235, 6.172, 0.479, 0.483, 3.343, 1.413, 0.207, 0.171, and 0.056 mg·g^-1. The results of HCA and OPLS-DA analysis show that 23 batches of A. souliei can be divided into two groups based on caffeic acid content. The content of the first group was between 0.873 to 5.647 mg·g^-1, while the second was between 8.524 to 16.705 mg·g^-1. This QAMS method can be used to simply and quickly evaluate the quality A. souliei.

This study identified the exact molecular mechanisms of baicalein on neuroinflammation in lipopolysaccharide (LPS)-induced BV-2 cells. Bioinformatics methods and molecular docking were integrated for predicting the potential targets and mechanisms of baicalein. Immunofluorescence staining and Western blot were used to analyze the predicted key targets [inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2)], the expression level of protein related to signal transducer and activator of transcription 1/nuclear factor kappa-B (STAT1/NF- κB) signaling pathway and its upstream regulator NADPH oxidase-2 (NOX2), and then the mechanism of baicalein in alleviating neuroinflammation was explored. The results showed that iNOS and COX-2 were predicted as the key targets and NF-κB signaling pathway was one of the important pathways by bioinformatics methods and molecular docking. Experimental verification showed that baicalein could significantly reduce the expression of iNOS and COX-2, inhibit the phosphorylation of NF-κB and STAT1 and the production of NOX2 in LPS-induced BV-2 cells. To sum up, baicalein could effectively inhibit the inflammatory reaction in LPS-induced BV-2 cells through regulating NOX2 (gp91^phox/p47^phox)/STAT1/NF-κB pathway.

Molecular mass distribution of Astragalus polysaccharides is wide. Astragalus polysaccharides prepared by conventional water extraction and alcohol precipitation are mostly mixture of macromolecules. Although studies have shown that Astragalus polysaccharides have two-sided immunomodulation, the relationship between anti-inflammatory components and molecular mass distribution of Astragalus polysaccharides is not clear. Therefore, Astragalus polysaccharides were extracted by water extraction and alcohol precipitation. The relative molecular weight of them was determined by high performance gel permeation chromatography (HPGPC). Astragalus polysaccharides with different molecular weights were separated and prepared by membrane separation. RAW 264.7 cells were induced by lipopolysaccharide (LPS) to establish an inflammatory cell model in vitro and the anti-inflammatory polysaccharide were screened. The anti-inflammatory regulation mechanism of Astragalus polysaccharides was analyzed by the LC-MS/MS metabonomics technology. The results showed that APS was composed of APS-Ⅰ (> 2 000 kDa) and APS-Ⅱ (10 kDa). APS-Ⅰ was composed of mannose, rhamnose, galacturonic acid, glucose, galactose, arabinose and the molar ratios of these monosaccharide of APS-Ⅰ were 0.54∶0.26∶12.24∶17.24∶8.46∶1. APS-Ⅱ was composed of rhamnose, galacturonic acid, glucose, galactose, arabinose and the molar ratios of these monosaccharide of APS-Ⅱ were 0.26∶0.14∶24.04∶0.62∶1. APS-Ⅰ and APS-Ⅱ had no cell toxicity to RAW 264.7 macrophage in the range of 0-100 μg·mL^-1. Compared with the model group, APS-Ⅰ at a concentration of 0-100 μg·mL^-1could significantly inhibit the secretion of NO and TNF-α by RAW 264.7, and can significantly promote the secretion of IL-10. APS-Ⅰ had better anti-inflammatory activity than APS-Ⅱ in vitro. The metabolomics results showed that 32 different metabolites were found between the model group and blank group; APS-Ⅰ group can significantly callback 18 different metabolites; mainly related to arginine biosynthesis, arginine and proline metabolism, pyrimidine metabolism, citric acid cycle (TCA cycle), cysteine and methionine acid metabolism, tryptophan metabolism. This study found that APS-Ⅰ had better anti-inflammatory activity than APS-Ⅱ in vitro, and its mechanism may be closely related to amino acid metabolism and energy metabolism, which indicated the direction for further clarifying the pharmacodynamic material basis of Astragalus polysaccharides.

Over the course of human civilization, viral infections have been a part of human life and still represent one of the heaviest burdens for human and society, with a huge devastating socioeconomic impact. Inorganic and bioinorganic chemistry have made important contributions to medical science and human health in the past half century. In this paper, we selected the representative cases in recent years, and reviewed the research progress of antiviral drug discovery from the perspective of bioinorganic chemistry.

Two new alkaloids along with eleven known ones, were isolated from the 70% ethanol extract of the roots of Scrophularia ningpoensis Hemsl. by various chromatographic methods, including silica gel, Sephadex LH-20, reverse phase C₁₈ and semi-preparative HPLC. Their structures were determined by physicochemical properties and spectroscopic methods, including UV, IR, MS, 1D/2D NMR and ECD. They were identified as 11α-isopropylcytisine (1), 13α-isopropylcytisine (2), uracil (3), (S)-5-hydroxypyrrolidin-2-one (4), pterolactam (5), methyl-L-pyroglutamate (6), kaempferide (7), luteolin (8), 5, 6, 7, 4′-tetramethoxyflavone (9), 6′-hydroxy-2′, 3′, 4, 4′-tetramethoxychalcone (10), scopolin (11), hymexelsin (12), and 8-hydroxycoumarin (13). Among them, compounds 1 and 2 are two new compounds, while compounds 3, 4, 7-12 were isolated from this plant for the first time. An antitumor activity assay showed that compounds 8 and 9 had weak cytotoxicity against breast cancer cells (4T1).

Cancer, also known as malignant tumor, is the second largest disease after heart disease, which is characterized by genomic instability and mutagenicity. Ataxia telangiectasia and RAD3-related kinase (ATR) are members of phosphatidylinositol 3-kinase (PIKK) family, belonging to serine/threonine kinase, one of the key kinases in DNA damage response (DDR) and DNA repair pathway. This paper reviews the latest progress in the ATR inhibitor field including mechanism of action (MOA), therapeutic applications, and the combination therapy from the perspective of medicinal chemistry. It also discusses the possible challenges and future directions of developing ATR inhibitor antitumor drugs, which could provide the scientists in this field the convenience for access the information and application guidance for clinical studies.

Recombinant humanized anti-ricin monoclonal antibody (MIL50) is a recombinant humanized monoclonal antibody targeting ricin. In this study, an ELISA method was used to establish a method for the determination of MIL50 in macaque serum, and a cross design method was used. Twelve rhesus monkeys were intravenously injected 1 mg·kg^-1 test preparation (MIL50 freeze-died powder injection) and reference preparation (MIL50 liquid preparation) to determine the plasma concentration of MIL50 at different time points, and the pharmacokinetic parameters were analyzed to compare the pharmacokinetic characteristics of MIL50 liquid preparation and freeze-died powder injection in rhesus monkeys. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of the Chinese Academy of Medical Sciences and Use of Laboratory Animals and the regulations derived by the Animal Care and Welfare Committee of the Institute of Radiation Medicine, Academy of Military Medical Sciences (IACUC-DWZX-2020-503). The results showed that there was no significant difference between C_max and AUC_0-5d in the two groups. The liquid preparation was the reference preparation, with C_max ratio of 101.6% and AUC_0-5d ratio of 101.9%, the 90% confidence interval of C_max was 79.42%-129.92%, and the 90% confidence interval of AUC_0-5d was 85.72%-121.18%. These results suggested that different dosage forms of MIL50 had certain differences in the changes of blood drug concentration in rhesus monkeys.

In recent years, the targeted protein degradation technology has developed quickly, with proteolysis-targeting chimera (PROTAC) as the best-known strategy through exploring the ubiquitin-proteasome system. A number of new targeted protein degradation strategies have been emerging to expand the scope of protein degradation technology, including lysosome-targeting chimeras (LYTACs), autophagy-targeting chimeras (AUTACs), autophagosome-tethering compounds (ATTECs) and chimeras based on chaperone-mediated autophagy (CMA). The emerging methodologies have explored another important protein degradation system in eukaryotes-lysosomal systems, such as the endosome-lysosome pathway and the autophagy-lysosome pathway. This review summaries the mechanisms and features of different strategies for targeted protein degradation, with a special emphasis on the new targeted protein degradation technologies, such as their current status, advantages and limitations.