Latest ArticlesSepsis is a refractory disease with high mortality in which the host's immune response to the infection is dysfunctional, resulting in life-threatening organ function damage. The pathogenesis of sepsis is complex, involving systemic inflammation, immunosuppressive and coagulation abnormalities, and endothelial barrier damage caused by the infecting pathogenic microorganisms and their toxins. The pathogenesis of sepsis is closely related to multiple systems disorder and multiple organ dysfunction and failure. In recent years, the incidence of sepsis has been increasing globally, with an annual increase of 9%. Since the development of sepsis does not depend on the infecting pathogenic microorganisms and the late inflammatory reaction can be life-threatening, clinical treatment of sepsis can be very difficult. However, the current antibiotic treatments for sepsis are not ideal. Most clinical treatments are not curative, so researchers seek new drug designs based on exploring molecular mechanisms of the pathophysiological process in sepsis patients. This paper reviews the recent development of drugs designed according to the sepsis pathophysiological process.
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.
"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.
Nitric oxide (NO) is widely present in peripheral and central nervous system and regulates many physiological functions. Sleep-arousal is an advanced physiological activity. Studies have shown that NO is involved in the regulation of sleep and arousal. Nitric oxide synthases (NOSs) are a family of enzymes that catalyze the production of NO from L-arginine. Through guanylate cyclase or S-nitrosation of protein, NO can affect the activity of the ascending reticular activating system to regulate the sleep-arousal process. This paper summarizes the production of NO, its effect on sleep-arousal and its mechanism in the ascending reticular activating system, and provides new ideas and directions for the study of sleep and arousal.
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 novel coronavirus pneumonia was first discovered in December 2019. By February 21, 2020, the virus had spread to 27 countries, and the total number of patients were nearly 80 thousands. In order to effec-tively prevent and control the epidemic, countries around the world are organizing scientific research, especially in screening of therapeutic drugs, researching and developing of vaccine, which is the key point and difficulty of epidemic control. On the basis of a large number of relevantly collected information about drugs and biological products in the academia and the press of various countries, this paper focus on the research status and develop-ment of antiviral chemical drugs, Chinese traditional medicines and biological products, aiming to provide refer-ence for relevant departments, units and scientists.
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.
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.
The ethyl acetate fraction of 80% ethanol extract from Bidens parviflora Willd.was isolated and purified by silica, polyamide, Sephadex LH-20 and HPLC. A total of eleven compounds were isolated and identified by physicochemical properties and spectral data as (2S)-11E-tetradecene-3, 5, 7, 9-tetrayne-1, 2, 13-triol (1), pyridine-4-formyl-O-β-D-glucopyranoside (2), maritimein (3), trichocarpine (4), okanin-4-methyl ether-3'-O-β-D-glucopyranoside (5), okanin-4-methyl ether-4'-O-β-D-(6″-acetyl)-glucopyranoside (6), (Z)-6-O-(4″-acetyl-6″-O-p-coumaroyl-β-D-glucopyranosyl)-6, 7, 3', 4'-tetrahydroxyaurone (7), quercetin-3-O-α-L-arabinoside (8), hyperoside (9), (3S)-(6E, 12E)-tetradecadiene-8, 10-diyne-1, 14-diol-3-O-β-D-glucopyranoside (10), bipinnata polyacetyloside B (11). Compounds 1 and 2 are new compounds, compounds 4 and 8 were isolated from the genus Bidens for the first time, compounds 5-7, 10 and 11 were isolated from this plant for the first time.
Butylphthalide and ferulic acid exhibit excellent therapeutic effects in ischemic stroke. In this research, twelve 3-n-butylphthalide derivatives were designed by molecular hybridization strategy. The target compounds were obtained by nucleophilic substitution, reduction reaction, esterification reaction and elimination reaction, and the structure was confirmed by 1H NMR, 13C NMR and ESI-MS. All compounds were evaluated for neuroprotective activity against OGD/R-induced neurotoxicity in rat cortical neurons by MTT assay. The compounds with the best neuroprotective activity were biologically evaluated for their ability to inhibit platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP) via the Bron method.The results indicate that 7b exhibited potent neurocyte protective activity as well as prominent anti-platelet aggregation activity. Compound 7b has potential to be developed as a drug for ischemic stroke.