Latest ArticlesBased on the dual needs of analgesia and anti-inflammation in trauma treatment, this study uses acetaminophen and moxifloxacin hydrochloride as active pharmaceutical ingredients and develops a composite bilayer tablet with a dual-phase drug release system by using binder jet 3D printing technology. Due to the complexity of the 3D printing process, there is an interaction between the various parameters. Through the optimization of the process, the relationship between the key process parameters can be determined more intuitively. In this study, the process of extended-release tablets was optimized to maintain the mechanical properties of the tablets while realizing the regulation of release. The full-factor experimental design of three central points 23 was used to analyze the factors that significantly affect the quality attributes of extended-release tablets and the interaction between factors. The optimal extended-release process parameters were obtained by the response optimizer: the inkjet quantity of the printing ink was 10 (about 13.8 pL), the powder thickness was 180 μm, and the running speed was 360 mm·s-1. The in vitro of release of 3D printed composite bilayer tablets showed that the in vitro of release of 3D printed tablets and commercially available tablets conformed to the Ritger-Peppas release model. The results of porosity showed that the immediate-release layer of the preparation has many pores and large pore size, and the dissolution of the immediate release layer within 15 min was greater than 85%. The internal pore size of the extended release layer is large, but it can still release slowly for up to 8 h, the mechanism may be related to the extended release of HPMC gelation. On the basis of verifying the rationality of the design goal of 3D printed composite bilayer tablets, this study also provides a theoretical basis for the preparation of 3D printing complex preparations.
The polymorphism and thermostability of nirmatrelvir, the main antiviral component of the oral COVID-19 treatment drug, were studied. Four polymorphs of nirmatrelvir were prepared by recrystallization methods. Among them, Form 1 and nirmatrelvir methyl tert-butyl ether solvate (Form 2) had been reported in the literature, while nirmatrelvir isobutyl acetate solvate (NMTW-IBAC) and nirmatrelvir ethyl acetate solvate (NMTW-EA) are two new solvates. The crystal structures were characterized by single-crystal X-ray diffraction, powder X-ray diffraction, thermogravimetric analysis and differential scanning calorimetry. The thermostability of polymorphism and crystalline transformation were also investigated by combining Hirshfeld surface analysis and interaction energy analysis. The results showed that nirmatrelvir Form 1 belongs orthorhombic crystal system with the space group P212121 and one nirmatrelvir molecule included in the asymmetric unit, which has the same crystal structure as nirmatrelvir Form 4 reported in the literature. Owing to its larger thermal expansion, the differences in crystallographic parameters obtained at different temperatures were found between Form 1 and Form 4. Three solvates of nirmatrelvir belonged to the iso-structural with monoclinic crystal system and the space group P21, in which the asymmetric unit contains one nirmatrelvir molecule and one solvent molecule. The thermal analysis results showed that nirmatrelvir Form 1 was a solvent-free crystal form with the best thermal stability and the strongest intermolecular hydrogen bonding. Among the three solvates, NMTW-EA has the worst thermal stability and the weakest hydrogen bonding interaction between the nirmatrelvir molecule and the solvent molecule. The energy framework of nirmatrelvir solvates showed that the closer the arrangement between solvent and nirmatrelvir molecules, the greater the total interaction energy between solvent and nirmatrelvir molecules. The phase transition studies of the three solvates showed that NMTW-IBAC and NMTW-EA were transformed into amorphous after desolvation, respectively, while Form 2 undergoes oiling during desolvation. The research provides theoretical guidance for the analysis, identification and quality control of nirmatrelvir polymorphs.
Cytochrome P450 (CYP450) is a kind of superfamily oxidase containing heme, which is distributed in various aerobic organisms. They are widely involved in the biosynthesis of terpenoids, alkaloids, flavonoids, fatty acids, etc. In this study, the full-length cDNA sequence of a P450 was cloned by reverse transcription-PCR (RT-PCR) and rapid amplification of cDNA ends (RACE) technology, with the specific primers that designed according to the sequence of a transcript annotated as P450 from the Aquilaria sinensis (Lour.) Gilg transcriptome database. The tissue expression and subcellular localization were also studied. The full-length cDNA of the cloned P450 gene is 1 920 bp, with 88 bp 5′-untranslated region (UTR), 344 bp 3′-UTR and a 21 bp polyA tail, and 1 488 bp open reading frame (ORF), encoding 495 amino acids. Sequence alignment revealed that the protein belonged to CYP71D family of cytochrome P450 family, and named AsCYP71D1. Tissue expression analysis indicated that AsCYP71D1 was mainly expressed in stem. Further subcellular localization of onion epidermis showed that AsCYP71D1 was expressed in cytoplasm, nucleus and cell membrane. This study will provide a foundation for further research on its function in agarwood sesquiterpene biosynthesis.
Analyze the changes in gene expression profiles during the process of Panax ginseng seed dormancy release, and screen for differential genes, providing a basis for analyzing the mechanism of P. ginseng seed dormancy release. Comparative transcriptome analysis was conducted by using RNA-Seq sequencing technology in P. ginseng seeds stored at different low temperature. A total of 80.97 Gb of Raw reads and 80.19 Gb of Clean reads were obtained from the transcriptome. Principal component analysis and correlation analysis showed that there were significant differences in gene expression patterns at different developmental stages. Upset results showed that 46 248 unigenes were co-expressed in four stages, and 414, 445, 400 and 389 unigenes were specifically expressed in 0, 8, 14 and 28 days, respectively. Gene Ontology functional annotation showed that the differentially expressed genes were mainly involved in nsaturated fatty acid biosynthetic process, nuclear body and oxidoreductase activity. Encyclopedia of Genes and Genomes metabolic pathway showed that differentially expressed genes were mainly involved in peroxisome, mitogen-activated protein kinase signaling pathway-plant, plant hormone signal transduction, ribosome, biosynthesis of unsaturated fatty acid, circadian rhythm-plant and other metabolic pathways. In the process of P. ginseng seed dormancy release, multiple biological processes, such as unsaturated fatty acid biosynthesis and plant hormone signal transduction, are required to coordinate regulation, which constitutes a complex dormancy release regulation network. Transcriptome analysis and differential gene screening of P. ginseng seeds at different sand storage time laid a foundation for the analysis of P. ginseng seed dormancy release mechanism and molecular breeding.
In the study, specific primers were designed based on the CO Ⅰ gene sequence of Polyrhachis dives. By optimizing the genomic DNA extraction method and amplification conditions, we established an efficient, specific, and accurate DNA molecular identification method for Polyrhachis dives. In this method, the length of the target fragment was 294-308 bp, and the other counterfeits had no target bands. In this paper, the specific identification method of the origin of Polyrhachis dives established can be used to identify the medicinal materials of Polyrhachis dives accurately.
As an important component of nucleosomes on the chromatin of eukaryotic cells, histones play an important role in the development and progression of tumour diseases by regulating epigenetic post-translational modifications such as acetylation and methylation. In addition, development of inhibitors targeting methyltransferase and deacetylase provides novel therapeutic strategies for cancer treatment. Mass spectrometry-based proteomics can reveal the global changes of histone modifications under the action of drugs during disease progression, which in turn provides important support for revealing drug action mechanism, drug resistance mechanism, and investigating novel drug combination strategies. This article focuses on the progress and status of proteomic research on a variety of histone modifying enzyme inhibitors, including methyltransferase inhibitors and histone deacetylase inhibitors, which will help to understand the current and further utilization of proteomics in studying histone modifications.
Single cell RNA sequencing (scRNA-seq) is an advanced technology to study the transcriptome information at the single cell level. The application of this technology can attribute to analyze the heterogeneous map of cells in the process of disease development, and precisely identify the specific cell subsets that are responsive to pharmacological therapy. Currently, scRNA-seq technology has been widely applied in the field of drug research, including studies on therapeutic targets, drug-induced adverse reactions, drug resistance and vaccine. This work reviews the application of scRNA-seq technology in drug discovery, which offers a scientific basis for personalized and accurate medication therapy.
A breakthrough in molecular biology for the twenty-first century is CRISPR/Cas gene editing, which has been used in a variety of fields due to its simplicity, adaptability, and targeting. Given the current global challenge of severe bacterial resistance, difficulties in detecting antimicrobial resistance, and slow development of antimicrobial drugs, CRISPR/Cas gene-editing technology offers a promising avenue for the development of antibacterial treatments. On the one hand, CRISPR/Cas gene editing technology helps advance the study of bacterial functions and serves as a toolbox. For instance, Cas proteins and exogenous repair systems enable efficient and precise gene editing, nCas proteins and deaminase systems facilitate template-free and single base precision editing, dCas proteins and reverse transcriptase allow for repair-free gene editing, and dCas proteins and modified sgRNA enable gene expression level regulation and gene function analysis. On the other hand, its specific gene recognition and targeted DNA cleavage characteristics can be used for pathogen detection, elimination of drug-resistant bacteria and genes, and hold promise as a new strategy for clinical diagnosis and treatment.
Autophagy is an important physiological process that can degrade cell components and maintain cell homeostasis, divided into three types including macroautophagy, microautophagy and chaperon-mediated autophagy generally, and macroautophagy is the most common form. Autophagy can affect the progression of a variety of diseases, such as cancer, neurodegenerative diseases, heart-related diseases, and autoimmune diseases, etc. However, autophagy can promote or inhibit diseases in different circumstances because of the dual roles of autophagy. Therefore, targeted regulating autophagy may be a potential treatment plan for diseases in specific stages of disease development. Now, with the development of traditional Chinese medicine (TCM) resources and the deepening of researches on the modern utilization of TCM, many active compounds from TCM have been discovered that can target autophagy to exert pharmacological activity. Most of the natural compounds activate or inhibit autophagy by affecting the classical PI3K/AKT/mTOR autophagy pathway. In addition, some compounds can also affect autophagy through MAPKs signaling pathways such as MEK/ERK, JNK and p38MAPK. These active compounds exert various biological activities by regulating autophagy, including anti-tumor, inhibiting neurodegenerative diseases, protecting cardiomyocytes, and relief of inflammatory response. In this review, we summarized the active compounds in TCM that affect autophagy by targeting different signaling pathways and their mechanisms of regulating autophagy, also introduced the effects of active compounds on diseases after affecting autophagy. Finally, this paper summarized and prospected the development of targeted autophagy for the treatment of diseases by TCM compounds, hoping to provide clues for subsequent exploration and research.
As a common protease with high similarity among coronavirus species, the main protease (Mpro) of SARS-CoV-2 is responsible for the catalytic hydrolysis of viral precursor proteins into functional proteins, which is essential for coronavirus replication and is one of the ideal targets for the development of broad-spectrum antiviral drugs. This paper reviews the main protease inhibitors of SARS-CoV-2, including their molecular structures, potencies and drug-like profiles, binding modes and structure-activity relationships, etc.
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