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.

G protein-coupled receptors (GPCRs), the largest family of transmembrane receptors in the human, contain seven transmembrane helices, and are usually regarded as critical drug targets because of their key roles in multiple diseases. Currently, 30%-40% approved drugs target GPCRs. Nanobodies (also known as single domain antibodies) are important research tools for GPCRs due to their small molecular weight, good biochemical properties and high affinity for "cracks or cavities". In addition, nanobodies have long complementarity determining region 3 (CDR3) loops which can be inserted deeply into GPCRs ligand binding pockets, efficiently binding to the folds. This review summarizes the characteristics of nanobodies and their applications in GPCRs research and briefly introduces the current identification routes of targeted GPCRs nanobodies, which could provide new idea and method for applications of nanobodies in GPCRs research.

The microbiome is a significant participant and driver of cancer development. Using traditional methods (such as antibiotics, probiotics, and microbiota transplantation) to regulate the microbiome has been proven to improve the therapeutic effect of cancer. But this type of method also has many limitations, such as the indirect damage to the symbiotic microbiota and the consistency of methodology. There is an urgent need to develop new technologies to solve these problems. Considering the success of nanotechnology in the field of cancer diagnosis and treatment, the use of nanotechnology to regulate the interaction between the microbiome and the tumor microenvironment is also expected to provide new and effective strategies for cancer treatment. In this review, we summarized the characteristics and advantages of various generations of nanotechnology, and reviewed the recent research related to the application of nanotechnology intervention to regulate the microbiome and its metabolites in cancer diagnosis and treatment, and discussed the challenges and future development prospects of this emerging field.

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.

To study the multivariate statistical analysis and metabolic regulation mechanism of rhubarb in the treatment of blood stasis syndrome through the ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS). In this study, multivariate statistical analysis was used to comprehensively analyze the differential characteristics of metabolites with significant regulatory effect in plasma samples of blood stasis model rats, analyze the changes of differential metabolites of rhubarb regulating blood stasis syndrome, and analyze the pathway enrichment of identified metabolites. The results showed that the differentiation of plasma differential metabolites between the model group and the control group was good (Q² > 0.5), and 44 differential metabolites all had different degrees of callback. The expressions of PC(15∶0/20∶2(11Z, 14Z)), PC(18∶1(9Z)/18∶1(9Z)), salicylaldehyde and glycolic acid were down-regulated in the rat model of blood stasis syndrome, and rhubarb could up-regulate them. The expression levels of (±)8-HETE, taurodeoxycholic acid and γ-murocholic acid were up-regulated in the blood stasis rat model, which could be down-regulated by rhubarb. Differential metabolites are enriched in 97 metabolic pathways, involving lipid metabolism pathways, inflammatory factors and immune pathways, and steroid hormone synthesis pathways. This study clarified the mechanism of rhubarb in the treatment of blood stasis syndrome from the perspective of plasma metabolism, and provided a theoretical basis for the further development and clinical application of rhubarb. This study has been approved by the experimental animal Ethics Committee of Shaanxi University of Traditional Chinese Medicine (No. SUCMDL202103009002).

Baihu-Guizhi Decoction (BHGZD), a prescription from ''Synopsis of the Golden Chamber'', has a definite clinical effect in the treatment of rheumatoid arthritis (RA). However, the research on the mechanism of this prescription mainly focuses on the regulation of inflammatory response and immune function, and its efficacy and mechanism of inhibiting synovial angiogenesis have not been reported. In the current study, transcriptomics data mining, biological network analysis and ''in vivo-in vitro'' experimental verification integrated research strategy to explore the potential and molecular mechanism of BHGZD in RA synovial angiogenesis with hot syndrome. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of China Academy of Chinese Medical Sciences. The results of network analysis showed that the candidate network targets of BHGZD intervention in RA with hot syndrome were significantly involved in multiple angiogenesis regulation related pathways. Among them, vascular endothelial growth factor A-vascular endothelial growth factor receptor 2 (VEGFA-VEGFR2) signaling pathway contains multiple BHGZD candidate network targets, such as VEGF, phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), etc. Further experimental results showed that BHGZD could effectively reduce the expression of CD31 in knee synovium, the expression level of VEGF in serum, the activity of endothelial nitric oxide synthase (eNOS), phosphorylated VEGFR2 (p-VEGFR2), p-PI3K and p-AKT in joint tissue of adjuvant-induced arthritis rats with hot syndromes, the migration and invasion activity of HUVEC and MH7A cells, and the lumen formation activity of HUVEC cells and improve the expression level of endostatin in serum. In conclusion, BHGZD has the potential to alleviate excessive synovial angiogenesis in RA with hot syndrome, and its mechanism may be related to the intervention of VEGF/VEGFR2/PI3K/AKT signaling pathway.

Electrospray ionization (ESI) is easy to be affected by the biological matrix interferences, and thus the accuracy, precision, and reproducibility of the quantitation are significantly impaired. Probe electrospray ionization (PESI) is one of the most typical ambient ionization, which can ionize molecules without complicated sample preparation at the atmospheric environment, and is superior in simplicity, high efficiency, and high throughput. The micro pen electrospray ionization tandem mass spectrometry (μPen-ESI-MS/MS) method was newly developed based on PESI. In this study, the matrix effect of the μPen-ESI-MS/MS method for drug quantitation in plasma samples was evaluated and compared with the liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method. The μPen-ESI-MS/MS and LC-ESI-MS/MS methods for quantitation of five drugs in rat plasma were established respectively, and the matrix factors (MFs) and internal standard normalised matrix factors (IS normalised MFs) were measured. The results showed that the ion suppression of the μPen-ESI-MS/MS method for tacrolimus, flunarizine, and desloratadine was equal to or less than that of the LC-ESI-MS/MS method; the RSDs of the IS normalised MFs of all five drugs were less than 15%, which met the related requirements of the Pharmacopoeia of the People's Republic of China. Therefore, this study investigated the matrix effect of the μPen-ESI-MS/MS method for quantitative analysis of target drugs in plasma samples and provided new data for the application of μPen-ESI-MS/MS in bioanalysis.

To profile and characterize the ingredients absorbed into blood and their metabolites of the Eucommiae Cortex (EC) extracts in rats with renal fibrosis induced by adenine, and so as to provide a reference for investigation of the pharmacodynamic substances of EC. SD rats with renal fibrosis induced by adenine were intragastrically administered with the EC extracts, and the rat plasma samples were collected and analyzed by UHPLC-Q-TOF-MS/MS to identify the prototype ingredients absorbed into blood and their metabolites. The experiment was approved by the experimental Animal Ethics Committee from Nanjing University of Chinese Medicine (No. 202103A008). The results showed that a total of 24 prototype compounds were identified, including 9 lignans, 4 iridoids, 8 phenylpropanoids, and 3 organic acids. Furthermore, 30 metabolites were obtained by further analysis, including 9 lignans, 19 iridoids, and 2 organic acids. The results of this study can provide the valuable reference for further elucidation of the pharmacodynamic substantial basis and mechanism of EC in the treatment of renal fibrosis.

Based on the chemical structure of known compound, 12 isatin derivatives palmitoyl transferase inhibitors are designed and synthesized using bioisosterism and molecular docking, while their anti-tumor activities in vitro are determined. The structures of the target compounds are confirmed by ¹H NMR, ¹³C NMR and HR-MS. In vitro anti-tumor assay illustrates that compound 5b exhibits similar anti-tumor activity to the control (IC₅₀ = 8.4 μmol·L^-1), with IC₅₀ value of 12.0 μmol·L^-1 against MCF-7 in which palmitoyl transferase is highly expressed. Compound 4b shows higher inhibitory activity against HeLa (IC₅₀ = 8.1 μmol·L^-1) than cisplatin (IC₅₀ = 40.1 μmol·L^-1). The molecular docking demonstrates that all compounds could completely enter the site of 3'-adenosine monophosphate-5'-diphosphate (PAP). Taken together, isatin derivatives represent promising compounds for the discovery of novel anti-tumor agents.

In order to study the chemical composition of Osmanthus fragrans var. thunbergii, the chemical constituents of the dried flower of O. fragrans var. thunbergii were studied. From the 95% ethanol extract of the dried flower, a new monoterpene (1), along with seven known monoterpenes, sesquiterpenes and phenethyl alcohols (2-8), was isolated and purified by silica gel, polyamide, and preparative reversed-phase HPLC chromatography methods. Their structures were identified by 1D-NMR (¹H NMR, ¹³C NMR, DEPT), 2D-NMR (HSQC, HMBC, ¹H-¹H COSY, NOESY), HR-ESI-MS, IR, UV, and its physical and chemical properties as: methyl (R, E)-2-(5-ethylidene-2-oxotetrahydro-2H-pyran-4-yl) acrylate (1), (R, E)-2, 6-dimethyloct-3, 7-dien-2, 6-diol (2), (6R)-2, 6-dimethyloct-7-en-2, 3, 6-triol (3), 2, 4, 4-trimethyl-3-(3-oxobutyl)-cyclohex-2-en-1-one (4), (S)-2, 4, 4-trimethyl-3-(3-hydroxybutyl)-cyclohex-2-en-1-one (5), (R, E)-2, 4, 4-trimethyl-3-(3-hydroxybut-1-en-1-yl)-cyclohex-2-en-1-one (6), (S, E)-3, 5, 5-trimethyl-4-hydroxy-4-(3-oxobut-1-en-1-yl)-cyclohex-2-en-1-one (7), and 2-p-acetoxyphenylethanol (8). 1 is a new compound, 2-8 were isolated from the plant of Osmanthus fragrans var. thunbergii for the first time.