Extracellular vesicles (EVs) are crucial for facilitating intercellular communication, promoting cell migration, and orchestrating the immune response. Recently, EVs can diagnose and treat tumors. EVs can be measured as biomarkers to provide information about the type of disease and therapeutic efficacy. Furthermore, EVs with lower immunogenicity and better biocompatibility are natural carriers of chemicals and gene drugs. Herein, we review the molecular composition, biogenesis, and separation methods of EVs. We also highlight the important role of EVs from different origins as biomarkers and drug delivery systems in tumor therapy. Finally, we provide deep insights into how EVs play a role in reversing the immunosuppressive microenvironment.

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

Objective To investigate the effect and mechanism of Liuling Jiedu Pills on acute pharyngitis caused by Staphylococcus aureus in rats.Methods The rat model of acute pharyngitis was replicated using the method of injecting 1×109 CFU·mL-1 of Staphylococcus aureus solution into the pharynx of rats.SD rats were randomly divided into a blank group,a model group,a Lanqin Oral Solution group(5 mL·kg-1),and a low-,medium-,and high-dose group of Liuling Jiedu Pills(4.375,8.750,and 17.500 mg·kg-1),with 10 rats in each group.Rats in each group were administered the drug by gavage once a day for 7 days.The general conditions of the rats were observed and recorded every day during the modeling and drug administration periods,and the local inflammation in the pharynx was scored;histopathological changes in the pharynx of the rats were observed by hematoxylin-eosin(HE)staining;serum interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor α(TNF-α),and tumor necrosis factor-α(TNF-α)were detected by ELISA.Immunohistochemistry and Western Blot were used to detect the protein expression levels of IL-1β,IL-6 and TNF-α in rat pharyngeal tissue.Results Compared with the blank group,rats in the model group had significantly increased pharyngeal erythema,significantly higher inflammation scores(P＜0.01),significantly lower body mass on days 5-7 after modeling(P＜0.05,P＜0.01),significantly higher pathological scores(P＜0.01),significantly higher levels of the serum inflammatory factors IL-1β,IL-6,and TNF-α(P＜0.01),and significantly higher pharyngeal tissues showed significantly higher levels of IL-1β,IL-6,and TNF-α proteins(P＜0.01).Compared with the model group,the pharyngeal erythema was significantly reduced in the Lanqin Oral Solution group and the low-,medium-and high-dose groups of Liuling Jiedu Pills,and the inflammation scores were significantly reduced(P＜0.01),and the serum levels of IL-1β,IL-6,and TNF-α were significantly reduced(P＜0.01);the body mass of the rats in the Lanqin Oral Solution group,and in the medium-and high-dose groups of Liuling Jiedu Pills,were significantly increased on the seventh day of the modeling(P＜0.01);the histopathological scores and the levels of IL-1β,IL-6 and TNF-α proteins in pharyngeal tissue were significantly decreased(P＜0.05,P＜0.01).Conclusion Liuling Jiedu Pills can significantly improve the symptoms and inflammatory pathological changes of pharyngeal tissues in rats with acute pharyngitis,and its mechanism may be related to the down-regulation of the expression levels of inflammatory factors such as IL-1β,IL-6,and TNF-α.

Due to the special physiological and pathological characteristics of gliomas, most therapeutic drugs are prevented from entering the brain. To improve the poor prognosis of existing therapies, researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy. Although these strategies can be used clinically to overcome the blood‒brain barrier (BBB), the accurate delivery of drugs to the glioma lesions cannot be ensured. Nano-drug delivery systems (NDDS) have been widely used for precise drug delivery. In recent years, researchers have gathered their wisdom to overcome barriers, so many well-designed NDDS have performed prominently in preclinical studies. These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions, drug release in response to the glioma microenvironment, biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein, and carriers created according to the active ingredients of traditional Chinese medicines. We reviewed these well-designed NDDS in detail. Furthermore, we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy, and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.

AIM To establish a quantitative analysis of multi-components by single-marker (QAMS) method for the simultaneous content determination of four saikosaponins in Xiaozheng Pellets (Bupleuri Radix,Cyperi Rhi-zoma,Rhei Radix et Rhizoma,etc.).METHODS The analysis of 5％ ammonia-methanol extract of this drug was performed on a Waters Xbridge C18column (250 mm ×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-water flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 210 nm and 254 nm.With saikosaponin a as a internal standard,the relative correction factors of saikosaponins b1,b2 and c were calculated,followed by the determination of their contents.RESULTS Four saikosaponins showed good linear relationships within their own ranges (r ≥ 0.999 5),whose average recoveries were 98.08％-102.94％ with the RSDs of 0.85％-1.82％.The results obtained by QAMS approximated those obtained by external standard method.CONCLUSION This simple,precise and feasible method can be used for the quality control of Xiaozheng Pellets.

AIM To establish the HPLC-ELSD fingerprints of oligosaccharide sites from mycelia of Hericium erinaceum solid cultures and Weilening Tablets.METHODS The analysis of aqueous extract from samples was performed on a 80 ℃ thermostatic Waters XBridge TM Amide column (4.6 mm × 150 mm,3.5 μm),with the mobile phase comprising of acetonitrile-0.2％ ammonium acetate flowing at 1 mL/min in a gradient elution manner.RESULTS There were eight and nine common peaks in two HPLC-ELSD fingerprints with the similarties of 0.994-0.966 and 0.990-0.997,respectively.Three of them were mannitol,lactose and trehalose,which showed good linear relationships within their own ranges (r ≥ 0.999 0),the average recoveries were 95.08％-104.82％ with the RSDs of 1.12％-2.90％.CONCLUSION This simple and accurate method can be used for the rapid quality control of mycelia of Hericium erinaceum solid cultures and Weilening Tablets.

Gut microbiota-mediated deglycosylationplays an important role in the metabolism of ginsenoside Rb1. Thus, a lincomycin-induced gut microbiota dysbiosis rat model was selected to explored the pharmacokinetics and deglycosylation metabolism of ginsenoside Rb1. An UPLC-MS/MS analytical method was developed to detect ginsenoside Rb1 and its deglycosylated metabolite, Rd in rat plasma. The triple quadruple mass spectrometer was set in negative electrospray ionization mode by multiple reaction monitoring. The method was validated to meet the requirements of biological applications, by evaluating specificity, linearity, lower limits of quantification(LLOQ), precision, accuracy, matrix effect, recovery and stability. Gut microbiota dysbiosis rats were induced by oral administration of lincomycin(5 000 mg/kg)for 7 continuous days. The in vitro and in vivo results reveal that the reduced β-D-glucosidase activity significantly decreases the Rd formation rate in lincomycin-induced gut microbiota dysbiosis rats, leading to the pharmacokinetic alteration of ginsenoside Rb1 and Rd in gut microbiota dysbiosis rats.

Objective To establish analysis methods for fingerprint of Chuanxiong Rhizoma by HPLC. Methods Thermo C18 chromatographic column (4.6 mm×250 mm, 5 μm) was used with methanol-0.1% Formic acid in gradient elution. The flow rate was 1 mL/min, the detection wavelength was set at 323 nm, and the temperature was 25 ℃. The similarities of the 18 batches of samples were compared by similarity evaluation, cluster analysis and principal component analysis. Results Based on the fingerprints of 18 batches of Chuanxiong Rhizoma, 11 common peaks were identified, the similarities were almost greater than 0.9 among all batches. The samples were clustered into 3 categories. Conclusion The method is simple, steady and repeatable. It provides a basis for the quality control and evaluation of Chuanxiong Rhizoma.

OBJECTIVETo observe abnormal metabolic changes caused by ischemic cerebral apoplexy and the regulating action of Tongsaimai pellets on abnormal metabolism by analyzing the change of small molecules in plasma of ischemic cerebral apoplexy rat. To find the potential biomarkers, and to explore metabolic mechanisms of Tongsaimai pellets.

METHODRat models of middle cerebral artery occlusion was established with electric coagulation, and rats were divided into 4 groups, model group, sham-operation group, Tongsaimai pellets group and positive control group. Tongsaimai pellets and positive control group were orally administrated by 13.2 g x kg(-1) x d(-1) of crude drugs and 32 mg x kg(-1) x d(-1) of Nimodipine respectively, m odel and sham-operation group by equal volume of distilled water for a week. Plasma of model and sham-operation group were collected, and plasma of Tongsaimai pellets and positive control group were collected on the 1st, 3rd , 7th day after administration. Endogenous metabolites of four groups were determined with GC-MS. Partial least squares discriminant analysis (PLS-DA) was applied to analyze multivariate data and set up model, and T-test was used in significant statistical analysis.

RESULTCompared with sham-operation group rats, pyruvic acid, taurine and hydroxyproline obviously increased in model group rats, while lactic acid, glyceric acid, aminomalonic acid, fructose, tryptophan and leucine significantly decreased, so these metabolites were potential metabolic biomarkers. These endogenous metabolites except taurine got restoration in Tongsaimai group rats.

CONCLUSIONAbnormal metabolite level in plasma can be certainly recovered by Tongsaimai pellets, and the treatment of Tongsaimai pellets can be connected with the regulation of related metabolic pathways.

Animals ; Brain Ischemia ; blood ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Fructose ; blood ; Glyceric Acids ; blood ; Hydroxyproline ; blood ; Lactic Acid ; blood ; Leucine ; blood ; Male ; Malonates ; blood ; Metabolomics ; methods ; Pyruvic Acid ; blood ; Rats ; Rats, Sprague-Dawley ; Stroke ; blood ; drug therapy ; Taurine ; blood ; Tryptophan ; blood

In this study, daphnetin and its major metabolites in the intestinal wall of rats were identified by liquid chromatography and quatrupole-time of flight mass spectrometry. Perfusion fluid of duodenum, jejunum, ileum and colon were collected separately for 2 hours from the rat intestine following perfusion with daphnetin. The metabolites of daphnetin in the perfusion fluid of different intestine segments were analyzed by the liquid chromatography and quatrupole-time of flight mass spectrometry. It is shown that the parent drug daphnetin and four metabolites were found in the perfusion fluid of duodenum, jejunum and ileum. However, no metabolites were found in the colon. Among the four metabolites, two daphnetin sulfates (m/z 257) were first discovered as the phase II metabolites of daphnetin in rats, which revealed a new way of daphnetin metabolism in rats.