Latest ArticlesGlycyrrhiza eurycarpa P.C.Li is a medicinal plant resource and is often mixed with traditional licorice herbs. We sequenced the chloroplast genome of Glycyrrhiza eurycarpa P.C.Li using Illumina high-throughput sequencing technology, and physical mapping and genomic characterization was carried out. Comparative genomic analysis was performed with Glycyrrhiza uralensis Fisch, Glycyrrhiza inflata Bat and Glycyrrhiza glabra L. The Glycyrrhiza eurycarpa P.C.Li chloroplast genome was 127 864 bp long with 34.25% GC content, consisting of a large single copy and a small single copy. The genome was missing the inverted repeat (IR) region. A total of 110 genes were annotated, including 76 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. The 301 SSRs, rich in A-T repeats, were detected by MISA. The Glycyrrhiza eurycarpa P.C.Li chloroplast genome showed weak codon preference, and the codons were biased to use A and T bases. Three specific gene fragments of Glycyrrhiza eurycarpa P.C.Li were characterized by homology comparison. Based on Pi analysis, six new high mutation regions (psbZ-psbC, trnC-GCA-rpoB, trnR-UCU-trnG-UCC, ycf2, trnN-GUU-ycf1, ndhA) of medicinal licorice species were determined. The results of phylogenetic analysis indicate that Glycyrrhiza eurycarpa P.C.Li from Xinjiang is an interspecific hybrid taxon closely related to the three medicinal licorice species, and Glycyrrhiza inflata Bat, which is distributed in the same domain, is its male parent. Based on this study, the taxonomic identification, herb-specific DNA fingerprint development, genetic diversity, and molecular plant breeding of medicinal plants of the genus Glycyrrhiza can be established.
On the basis of the Uncaria transcriptome, specific primers were designed for UrSTR. The full-length cDNA of UrSTR (GeneBank: OL310251) was 1 541 bp, encoding 345 amino acid residues, and the promoter region sequence of UrSTR (GeneBank: OL310252) was 1 179 bp. Phylogenetic tree is revealed that UrSTR had a closest relationship with STR from Ophiorrhiza pumila and Ophiorrhiza japonica. Localization of UrSTR protein is revealed located in the vacuole membrane. Plant-care analysis indicated that the promoter region sequence of UrSTR, covering multiple light, stress and hormone-response cis-regulatory elements, and verified transcriptional activity. The results of SDS-PAGE show that pET-28a-UrSTR recombinant protein was successfully expressed, and the size was anticipated. The UrSTR prokaryotic expression system needs to be optimized in the later stage. The research lays the foundation for further purification to study its structure and functional characterization of the UrSTR protein.
Coronavirus disease 2019 (COVID-19) continues to be prevalent all over the world and mutant strains are constantly appearing, the application of vaccine is still an important method of epidemic prevention and control. Mucosal immunity plays an important role in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion. The currently marketed injectable COVID-19 vaccine mainly activates humoral immunity, but it is difficult to induce effective mucosal immunity, and it is unable to prevent pathogen invasion in the early stage of virus infection. Compared with injection vaccination, inoculation of the COVID-19 vaccine through mucosal routes such as nasal or oral can closely imitate the natural infection pathway of the virus and induce a comprehensive immune response. It is an ideal choice for rapid and extensive vaccination because it has the advantages of simple and convenient use, easy to achieve self-management of vaccinators, reduced demand for professional medical personnel and so on. In this paper, we summarized and analyzed the products and technical platforms of COVID-19 vaccine inoculated by oral route, in order to provide reference for related research work.
The success of new drug discovery in 2021 can be affirmative, although the whole world is still suffering from COVID-19 pandemic. 50 new drugs were approved by the FDA's Center for Drug Evaluation and Research (CDER) last year. Among them, 27 were defined as first-in-class drugs, accounting for the highest number in the past decade. Notably, small molecule drugs still occupy a dominant position in first-in-class drugs with 15 drugs approved. Some of them were regarded as milestones for the drug discovery including sotorasib, a first small molecular covalent inhibitor targeting the "undruggable" target of the KRAS G12C; asciminib, a first small molecular allosteric inhibitor targeting the allosteric pocket of BCR-ABL1; belzutifan, a first small molecular inhibitor to inhibit HIF-2α; and vericiguat, a first small molecular sGC agonist for the treatment of chronic heart failure (CHF). First-in-class drugs rely on the discovery of novel targets and biological mechanisms, thus requiring different drug design approaches and being important guidance. In this review, we expect to provide research ideas and methods for more first-in-class drugs based on the research background, development process and therapeutic application of 3 first-in-class small molecule drugs in 2021.
Liver fibrosis is characterized by scarring of liver tissue, which is an intermediate pathological process of chronic liver disease developing into liver cancer. Its mechanism involves multiple signal pathways, and its reversibility is a current research hotspot. Bone marrow mesenchymal stem cells (BMSCs) are adult stem cells with multi-differentiation potential. They have ability to differentiate into liver-like cells in vivo and in vitro to perform normal liver cell functions. Modern pharmacological experimental studies have shown that the use of BMSCs alone or in combination with active factors, Chinese medicine or Chinese medicine monomers, genetic modification and other methods can promote their proliferation, differentiation, and migration, improve the therapeutic effect, and play a role in improving liver fibrosis. By summarizing the existing literature, the therapeutic mechanism of BMSCs in improving liver fibrosis is reviewed from the aspects of the pathogenesis of liver fibrosis, the improvement mechanism of liver fibrosis, the biological characteristics of BMSCs and its improvement mechanism, so as to provide reference for the later development of BMSCs cell therapy.
Recombinant human granulocyte colony stimulating factor (rhG-CSF) has been in clinical use for the adjuvant therapy of cancer patients with neutropenia caused by radiotherapy/chemotherapy. However, it does have some drawbacks such as poor stability and short half-life, and needs to be administered repeatedly, which is easy to cause adverse reactions such as drug tolerance and immune rejection. Therefore, it is necessary to develop long-acting rhG-CSF to improve its clinical efficacy. In this review, we summarize the research progress on the development of long-acting rhG-CSF using the strategies such as PEGylation, fusion protein and new dosage forms in recent years, and discuss its future development trend.
Pyroptosis is a form of inflammatory programmed cell death pathway. In vitro and in vivo studies have shown that pyroptosis contributes to the development of macrovascular complications of diabetes, mainly through activating inflammasomes and caspase-1/4/5/11, cleaving gasdermin D (GSDMD), releasing interleukin-18 (IL-18), IL-1β and other inflammatory cytokines. In recent years, the effect of systemic chronic inflammation caused by pyroptosis through inflammatory cascade reaction on macrovascular complications of diabetes has received long-term attention. This article reviews studies of pyroptosis in macrovascular complications of diabetes and the related drugs to provide promising thought for treating macrovascular complications of diabetes in clinical.
Tuberculosis (TB) is an enduring threat to global health. The epidemic persists with growing drug resistance, especially for extensively drug-resistant TB. Therefore, the treatment for TB and its associated multidrug resistance has been an ongoing challenge. Due to the greater attention and investment in the elimination of this disease, significant progress has been achieved. Bedaquiline, delamanid, and pretomanid have been approved for the clinical use. In addition, two dozens new anti-TB drugs are currently in clinical testing. China has contributed four new drugs TBI-223, TBI-166, aulimanid, and WX-081. The aim of this review is to summarize the recent advances in anti-TB drug development. Based on the different clinical stages of these anti-TB drugs, we mainly focus on mechanism of action, in vitro and in vivo pharmacological studies, pharmacokinetics and clinical studies.
Viral infections pose a persistent threat to human health and life. The rapid emergence of drug-resistant strains and the outbreak of new viruses require researchers to develop innovative strategies to accelerate the development of more antiviral drugs towards novel targets to meet the clinical needs. This paper selects typical research cases and reviews the novel targets and strategies of antiviral drugs in recent years from the perspective of medicinal chemistry.
Histone deacetylases (HDACs) are a class of key enzymes that regulate epigenetics. There are 5 small-molecule HDACs inhibitors having been approved for anti-cancer therapy on the market. In recent years, there have been more and more studies on the antiviral aspects of HDACs inhibitors. This article classifies viruses into human immunodeficiency virus 1 (HIV-1), new coronavirus (SARS-CoV-2), Epstein-Barr virus (EBV) and other viruses, systematically summarizes the recent advances of antiviral effects of the HDACs inhibitors from the perspective of medicinal chemistry. This review aims to provide the researchers the convenience of accessing the latest advances of the antiviral effects of HDACs inhibitors, and to analyze the challenges and prospects of this field in future drug discovery.
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