Atherosclerosis is one of the causes of many cardiovascular diseases. Lipid metabolism disorder is an important risk factor for atherosclerosis. Lipase-targeted screening may help discovery of hypolipidemic and anti-atherosclerotic drugs. Traditional methods for enzyme-based screening exhibit drawbacks of tedious operation steps, reduced enzyme activity, slow mass transfer, as well as high false positive rate. In this paper, an integrated perfusion enzyme affinity selection system based on hollow fiber was constructed to screen hypolipidemic and anti-atherosclerotic compounds from traditional Chinese medicines, and the total saponins of Kudingcha were taken as a case. First, we built a hollow fiber based perfusion system and optimized the methodology for enzyme affinity selection. Then, two active compounds of kudinosides A and C were identified as potential lipase inhibitors from the total saponins of Kudingcha by the proposed system. Last, the activity of kudinosides A and C was verified by lipase inhibitory assay and formation of foam cell model induced by low density lipoprotein aggregates, exhibiting the reliability of the system. This platform shows the advantages of integration, fast mass transfer, simple operation, low cost, as well as improved throughput and efficiency, which is especially suitable for rapid screening active components from traditional Chinese medicine.

The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout China and many other countries around the world. The antivirals are important measures to this epidemic; however, there is no drug approved for against coronavirus yet. With the continuously rising number of confirmed/suspected cases of COVID-19, it is urgent to obtain antiviral drugs for the clinical treatment. In response to this situation, drug repurposing strategy becomes one of the best approaches for anti-SARS-CoV-2 drug discovery. By retrieving the clinical trials registered in Chinese Clinical Trial Registry and ClinicalTrials.gov, a total of 14 chemical drugs were registered for COVID-19. In this review, we summarize and analyze the 14 drugs' indications, targets, and research basis related to the activities against viral infections, esp. coronavirus infections. We are making efforts to understand the evidence basis of these drugs for the treatment of SARS-CoV-2 infection applied by various research and clinical institutions in response to this COVID-19 outbreak, and also providing clues for quick response to possible epidemic in future and reasonable expansion of the indications of drugs.

Depression, a chronic syndrome with low mood, pessimism, cognitive and sleep disorders, is characterized by high incidence, high suicide rate, low consultation and treatment rate. 40%-50% of the risk of depression comes from genes, so studying on gene abnormalities serves as an important part of the research in the internal causes of depression, among which the receptor gene abnormalities are crucial factors. The study of potential receptor gene loci is expected to be new target for the treatment of depression in the future, which can provide theoretical basis for the early diagnosis, prevention and treatment of depression.

Mediator complexes involved in skeletal muscle metabolic processes have become a hot research topic in recent years. The mediator complex is a multi-protein complex which participates in transcription by bridging specific transcription factors and basal transcriptional machinery (RNA polymerase II). Mediator complexes are involved in regulating the expression of transcription factors related to skeletal muscle metabolism and muscle fiber transformation, such as PPARs and PGC1α. These mediators participate in skeletal muscle glucose metabolism by regulating glucose transporter GLUT4 and key transcription factors of metabolic pathways. In addition, they regulate metabolic diseases by regulating the expression of PPARγ, UCP-1 and other genes involved in skeletal muscle lipid metabolism and mitochondrial functions. This article reviews the mechanism and effects of mediator complexes on skeletal muscle metabolism.

"TCM syndrome of plague attack lung" is a classification of traditional Chinese medicine syndromes of the novel coronavirus pneumonia by the Beijing Municipal Administration of Traditional Chinese Medicine. In this study, a mouse model combining disease with syndrome of human coronavirus pneumonia with cold-dampness pestilence attacking the lung was established for the first time, and the therapeutic effect of matrine sodium chloride injection was evaluated based on immune regulation and inflammatory damage. Lung index, lung index inhibition rate and HE stain were used to evaluate the therapeutic effect of matrine sodium chloride injection on the model mice; the viral load in lung tissue was measured by RT-PCR to evaluate its antiviral effect; the percentage of CD4⁺T cells, CD8⁺T cells and B cells were detected by flow cytometry to evaluate its immunomodulatory effect; the production of interleukin 6 (IL-6), IL-10, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by ELISA to evaluate its anti-inflammatory effect. All interventions and operations in the experiment were approved by the Animal Ethics Committee of the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, and conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH) and Beijing Experimental Animal Ethics Committee. The results showed that intraperitoneal injection of the high-dose (36.67 mL·kg^-1·d^-1) and low-dose (18.33 mL·kg^-1·d^-1) of matrine sodium chloride injection significantly improved the pathological damage of lung tissue and reduced lung index. The lung index inhibition rates were 86.86% and 76.53%, respectively. The production of IL-6, IL-10, TNF-α, IFN-γ, as well as the viral load in lung tissue were reduced significantly compared to the model; the percentage of CD4⁺T cells, CD8⁺T cells and B cells in peripheral blood were increased compared to the model. These results indicated that the matrine sodium chloride injection has an evident therapeutic effect on the model, and its mechanism was related to the inhibition virus replication, regulation of immunity function and inhibition of inflammatory factor release. This study provided laboratory data support for matrine sodium chloride injection which was used to treat the novel coronavirus pneumonia in clinical in Hubei province. These results indicated that the matrine sodium chloride injection has a good prospect for prevention and treatment of the novel coronavirus pneumonia.

Liquid chromatography-tandem mass spectrometry (LC-MS) is a promising alternative or complementary method for traditional ligand-binding assays (LBA) in antibody drug bioanalysis. However, issues related to method development, sample preparation, sensitivity and quantitative accuracy need to be addressed. This paper reviews progress in bioanalysis of antibody drugs by LC-MS methods, introduces the principle of the LC-MS method for the analysis of antibody drugs, and describes the challenges faced in quantitative antibody analysis by the LC-MS method. New strategies that can be used to deal with these challenges include:selection of surrogate peptides, purification and enrichment of samples, improvement in enzymatic digest efficiency, enrichment of peptides, and use of low rate LC. We review the application of LC-MS technology in the biological analysis of antibody drugs and discuss the prospect of using the LC-MS method for the analysis of antibody drugs.

In this study, an immunostimulating particulate β-glucan was isolated from a hot alkaline extract of the fruiting bodies of Ganoderma lucidum. The optimum conditions of 8 hours treatment time, 1:20 solid-liquid ratio and 55℃ for the alkaline extract process were obtained after investigating by single-factor experiments and Box-Benhnken design in terms of the Ganoderma lucidum particulate β-glucan (GLG) increment, and these conditions resulted in a GLG yield of 8.57%. The experimental protocol was approved by the Medical Laboratory Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine. The result showed that resident macrophages were effectively activated by GLG, such as with the up-regulation of co-stimulatory molecules, the secretion of cytokines and phagocytic uptake. GLG could also promote the proliferation of spleen lymphocytes in mice. In addition, IFN-γ production of spleen CD4⁺T cells and cytotoxic T lymphocyte (CTL) responses were significantly enhanced on GLG orally treatment, which ultimately resulted in significantly decreased tumor burden. Taken together, these data suggest that GLG might act as an immune stimulator to exert antitumor effects.

A sensitive and simple high-performance liquid chromatographic tandem mass spectrometric (LC-MS/MS) method for the determination of verapamil and norverapamil in human plasma was established and utilized in a pharmacokinetic study in healthy patients. Protein was precipitated by methanol in plasma samples, and the analytes and internal standard were separated on an Agilent Zorbax Eclipse C₁₈ column (50 mm×4.6 mm, 5 μm) with a gradient procedure using methanol-acetonitrile (50:50) as the organic phase and 0.1% formic acid-5% acetonitrile-10 mmol·L^-1 ammonium formate solution as the mobile phase at flow rate of 0.5 mL·min^-1. Electrospray ionization (ESI) and multiple reaction monitoring (MRM) detection modes were used for quantitative detection of verapamil, norverapamil and verapamil-d₆ (IS). In the mode of multiple reaction monitoring of positive-ions, the monitoring ion pairs of verapamil, norverapamil and the verapamil-d₆ were m/z 445.0→165.2, m/z 441.0→165.2 and m/z 461.1→165.2, respectively. The quantitative lower limit (LLOQ) for the determination of verapamil and norverapamil concentrations in human plasma can reach 0.1 ng·mL^-1 in this assay. The calibration curve concentration ranged from 0.1 to 50 ng·mL^-1 with high linearity (r²>0.997). The matrix effect of verapamil and norverapamil was 99.2%-100% and 101%-102%, respectively. The recovery of verapamil and norverapamil was 86.8%-95.9% and 87.4%-94.8%, respectively. This method has good specificity and high sensitivity. The determination of the verapamil and norverapamil was not subject to the matrix effect and stable extraction recovery was achieved in this assay. This method could be used to determine the concentration of verapamil and norverapamil in human plasma and suitable for human pharmacokinetic studies after approved by ethics committee.

Most peptides have high binding affinity and good selectivity for endogenous receptors and are good lead compounds to develop into drugs. Many approved drugs are derived from the structural optimization of peptide molecules, such as the antihypertensive drug captopril and the anti-hepatitis C drug telaprevir. At present, the main problems in the development of peptide drugs include poor stability, short half-life, and high plasma clearance rate; lack of oral availability and poor patient compliance, a complex production process, and high production cost. Therefore, rational modification of peptides can not only reduce the production cost, but also improve the druggability of the peptides. Here we review structural modification strategies for peptides from the perspective of improving their physicochemical properties. These modification strategies are divided into two parts:one is modification of the peptide backbone, including unnatural amino acid modification, pseudopeptide strategy, inverse-peptide strategy, cyclization strategy, and terminal structure modification. Another is modification of the side chains of peptides, including fatty acid conjugation, polyethylene glycol conjugation, protein fusion strategy, and cholesterol conjugation.

Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway as an essential immune response pathway in cytoplasm, can find cytoplasmic DNA to regulate the innate immune and adaptive immune response. Studies have shown that the signaling pathway can be activated by both tumor self-DNA and genomic instability, thus to promote or inhibit the development and metastasis of tumors. Therefore, the role of cGAS-STING in tumor genesis, development and metastasis will be systematically expounded from the structures, physiological functions, inhibitors and agonists of cGAS and STING as well as its pathway transduction regulation in this paper. The paper aims to offer theoretical basis and reference for targeting cGAS-STING anti-tumor drugs in clinical practice and cancer clinical and cancer research workers.