Latest ArticlesCoronavirus disease 2019 (COVID-19), caused by the novel coronavirus (SARS-CoV-2) is treated in accordance with symptoms, which is feasible and effective. However, current therapeutic drugs are ineffective against this virus. The development of targeted therapeutic drugs that are based on key proteins in SARS-CoV-2 replication and pathogenesis will provide a more effective means for clinical treatment. In addition, because SARS-CoV-2 is an RNA virus, which typically mutate readily, new drug development against COVID-19 will be a long-term and arduous task. New approaches to drug discovery for COVID-19 treatment using molecular simulation and machine learning algorithms, and based on the key proteins in the process of SARS-CoV-2 adsorption, entry into the host cell and viral replication are discussed herein, and we briefly introduce related work in our laboratory that can provide strategies to promote the discovery of drugs with different mechanisms of action.
Heart failure is a serious public health problem with tens of millions of people suffering from its poor prognosis. Epidemiological studies indicate that its morbidity is rising year by year and its mortality has dramatically increased in recent years, with a trend towards younger people. Although great progress has been achieved in the development of medicine in recent years, finding effective agents against heart failure remains an unconquered area in medicine development. A large number of natural medicines and their bioactive compounds, possessing mild and low toxicity as well as multiple target comprehensive effects, have been implicated in a wide range of pharmacological properties in recovering heart function, reducing energy barriers, and improving the life quality of patients. In recent years, they have been widely applied in clinical treatment for heart failure. Hence, summarizing and elucidating the convincing mechanisms for these natural medicines and their bioactive compounds would provide therapeutic targets and benefits for the treatment against heart failure.
Fc region of a monoclonal antibody usually contains two N-glycosylation, which have a profound influence on its structure and function. Here, we review the relationship between various glycoforms and their impact on structure and function of monoclonal antibodies, along with the technologies for glycosylation analysis. In addition, some related Chemistry, Manufacturing and Controls (CMC) regulatory considerations are also discussed, such as specification improvement, biosimilarity assessment as well as comparability of pre- and post-process changes in glycosylation.
This study aimed to establish a method for identification of the prescription components of Pule'an Tablet based on DNA barcoding technology. Sixteen samples have been collected from 8 different companies, and their DNA were purified using Plant and Animal Genomic Kits. The amplification rates of ITS2 were both 100%, and the amplification rates of COI were 43.75% and 56.25% for these samples' DNA purified using plant and animal kits, respectively. For ITS2, 12 samples obtained high-quality sequencing traces and then were identified as containing Brassica campestris. The other 4 samples showed crucial SNP peaks in the sequencing traces, which were assigned to be B. campestris and B. nigra on the basis of cloning and sequencing experiments. For the PCR products of 9 samples from COI universal primers, two samples were directly sequenced and identified as aphids, and 7 other samples were subjected to cloning and sequencing experiments. Finally, we obtained 82 clone sequences and found that Apis mellifera was detected only in 5 of the remaining 7 samples, and pathogens or pests were detected in all these 7 samples. To solve the failure of bee source detection caused by exogenous contaminations based on COI universal primers, we designed two new COI primer pairs of Apis genus. The amplification rates of both primer pairs were 43.75%, and they were identified as A. mellifera. A total of 9 bee source-free Pule'an Tablet samples from 3 different batches were produced by the same company, and each batch contained 3 replicates. Thus, we speculated that raw rape pollen materials for these 9 samples was not collected by bees. This study proposes an identification method for the prescription components of Pule'an Tablets based on ITS2 and COI sequences, which will provide scientific basis and technical guidance for quality control and market regulation of Pule'an Tablets.
The quality of the same herbal medicines in different daodi-origins in China is significantly different. Our research team previously found that using protocatechuic acid as a chemical marker can divide the Cynomorium songaricum into outside-the Great Wall (Inner Mongolia) and inside-the Great Wall (Gansu). However, the ecological mechanism that causes the quality variation of C. songaricum is unclear. Based on the microbiome-ecological strategy, 16s amplicon sequencing was performed on rhizosphere soils of C. songaricum in two origins (Inner Mongolia and Gansu), and the composition of soil microbial communities was analyzed. Tax4Fun was used to predict the metabolic function of soil microbial communities. Correlation analysis by combing with the abundance of key microbial community and ecological climate factors was performed. Microbiome sequencing results revealed that the diversity of soil microbial communities in Inner Mongolia was significantly higher than that in Gansu. Five core microbiomes (Arthrobacter, Streptomyces, Bacillus, etc.) and six specific biomarkers of soil microbial communities (Microbulbifer, Methyloceanibacter, Cynomorium_coccineum, etc.) which could be distinguished from two origins were identified. For the first time, metabolic function prediction showed the metabolic function profile of soil microbiome of C. songaricum in two origins. Redundancy analysis and correlation analysis results showed that the annual sunshine hours was the main ecological factor affecting the composition of the soil microbial community of C. songaricum, and it was extremely significantly negatively related to Streptomyces and Bacillus. This article provides a new idea for explaining the formation mechanism of quality variation in the daodi-origins of C. songaricum, and also provides a scientific basis for theoretical research on the quality ecology of herbal medicines.
Fifteen 9-substituted palmatine (1) derivatives were synthesized and evaluated for their anti-Helicobacter pylori (Hp) activities in vitro. Structure-activity relationship studies revealed that introducing appropriate substituted secondary amino group at position 9 of lead 1 might be beneficial for potency. Among them, compound 5a showed the most potential activity against metronidazole (Met) resistant Hp isolates with minimal inhibitory concentrations (MICs) of 4 μg·mL-1, much better than that of lead 1. Compound 5a displayed satisfactory safety profile in acute toxicity assay. Molecular docking suggested that 5a might act on Hp urease. The results provided key scientific evidence for the development of 1 derivatives into a new class of anti-Hp component.
In this study, we used molecular docking technology and validation experiments in vitro to screen the active ingredients of Erzhi pill for treating osteoporosis. Firstly, the compound in Erzhi pill was docked with ten osteoporosis-related targets by molecular docking technology, and the five active compounds, salidroside, specnuezhenide, tyrosol, quercetin, and wedelolactone, were initially selected. Then, MC3T3-E1 osteoblasts were cultured in α-Mem medium containing different concentrations of compounds, and the cell proliferation rate and mineralized nodules were tested. The verification results showed that the proliferation of MC3T3-E1 cells with salidroside, specnuezhenide and quercetin were more obvious, and salidroside has a better effect on the mineralization of MC3T3-E1 cells than those of specnuezhenide and tyrosol. The molecular docking technology coupled with validation experiment in vitro can be used for the screening of anti-osteoporotic active ingredients of Erzhi pill, and it can also provide a method for the study of effective ingredients of traditional Chinese medicine.
Asparagus cochinchinensis is a commonly used traditional Chinese medicine with steroidal saponins as its main active ingredients. Due to the structural similarity and size of the steroidal saponins, these compounds cannot always be effectively separated by a combination of normal phase silica gel column chromatography and reversed phase ODS column chromatography. In this experiment, chromatographic columns with different separation mechanisms were systematically screened, and it was found that a chiral chromatographic cellulose column could effectively separate these components. This column was used to separate 3 mixtures to obtain 6 single compounds (1-6). Structural identification showed that the singular structural difference between these poorly separated components resides in a terminal glycosyl group (xylose or rhamnose) in the C-3 glycosyl chain, and compounds 4 and 6 are two new steroidal saponins. Since the structures of compounds are often unknown during the isolation and purification of natural products, chiral columns are rarely used. This study suggests that chiral chromatographic columns are a valuable option for natural products that are difficult to separate by conventional means.
The structural modification of nano-micellar polymer carriers can not only increase the solubilization of insoluble drugs, but also make drug-loaded carriers aggregate in tumor tissues. In this paper, paclitaxel (PTX) was used as a model drug, D-α-tocopherol polyethyleneglycol 1 000 succinate (TPGS) modified by disulfide bond (-S-S-) and oleic acid (OA) was synthesized and mixed micelles were prepared with different molar ratios of sodium deoxycholate (NADC), and TPGS and NADC mixed micelles modified by thioether bond were synthesized for comparative study. The effects of the critical micelle concentration (CMC) of the modified polymer and the molar ratio of TPGS-OA and NADC on the physical and chemical properties of the micelle were investigated. Finally, the redox drug release ability of disulfide bond and thioether bond was compared. The results showed that when the molar ratio of TPGS-OA to NADC decreased, the drug loading increased, but the stability decreased. When the molar ratio was 3:1, the particle size, potential and entrapment efficiency of TPGS-S-S-OA/NADC were 96.24 ±0.14 nm, -24.4 mV and (98.7 ±0.08)%, respectively, hemolysis rate of mixed micelles is less than 2%. The disulfide modified mixed micelles released PTX completely within 5 h in 10 mmol·L-1 H2O2 environment (pH 7.4), which was similar to that of thioether modified micelles. It was also found that the stability of micelles decreased when the pH value was low. All animal experiments were in accordance with ethical standards and were approved by the Animal Experimental Center of Shenyang Pharmaceutical University (No.211002300032403). In this study, we mainly developed stable nano-micelle carriers which can target drug release in tumor heterogeneous environment.
Cyclophosphamide (CPA) is the first-line chemotherapy for many tumors, but its overdose will lead to hepatotoxicity. This study aims to investigate whether the combined administration of oxymatrine (OMT) with CPA will aggravate the hepatotoxicity induced by CPA and its engaged mechanism. The expression of hepatic Cyp2b10 mRNA and CYP2B10 protein was detected by qPCR and Western blot in mice at different times after OMT (100 mg·kg-1) administration. Mice were given with different doses of OMT (intragastric administration, ig) every day. At the same time, CPA (200 mg·kg-1) was also intraperitoneally injected into mice every other day. After 10 days, serum alanine/aspartate aminotransferase (ALT/AST) activity, the mortality of mice and hepatic mRNA expression of Cyp2b10 were detected. Furthermore, the correlation among ALT/AST activity, the mortality and Cyp2b10 mRNA expression was analyzed. All animals were received humane care according to the institutional animal care guidelines approved by the Experimental Animal Ethical Committee of Shanghai University of Traditional Chinese Medicine. The results showed that OMT itself enhanced hepatic mRNA and protein expression of Cyp2b10 (P < 0.05), and increased liver enzymatic activity of CYP2B10 in mice (P < 0.05). In mice treated with CPA plus OMT, OMT obviously enhanced the mortality of mice induced by CPA (from 33.3% to 58.3%). The results of serum biochemical analysis and hepatic mRNA expression of Cyp2b10 showed that OMT further enhanced the increased serum ALT/AST activity and hepatic Cyp2b10 mRNA expression in mice (P < 0.05). There was a good correlation between serum ALT/AST activity and mortality or hepatic Cyp2b10 mRNA expression. These results showed that OMT could enhance hepatic Cyp2b10 mRNA expression and increase liver CYP2B10 enzymatic activity, and then promoted the metabolism of CPA, and thus aggravated CPA-induced hepatotoxicity in mice.
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