Although numbers of naked antibodies showing clinical efficacy as single agents, their therapeutic effect is limited. Chemotherapy is very effective but with relatively large side effects, so conjugation of small chemotherapeutic drugs to antibodies is one of the important methods to enhance therapeutic potential of antibodies. Antibody-drug conjugates (ADCs) represent a promising therapeutic approach for cancer patients by combining the antigen-targeting specificity of monoclonal antibodies (mAbs) with the cytotoxic potency of chemotherapeutic drugs. These modified antibodies are expected to selectively deliver chemotherapeutic drugs to tumor cells and provide sustained clinical benefit to cancer patients, at the same time, minimizing systemic toxicity. ADCs are expected to bring together the benefits of highly potent drugs on the one hand and selective binders of specific tumor antigens on the other hand. However, designing an ADC is very complex, requiring thoughtful combination of antibody, linker, and payload drugs in the context of a target and a defined cancer indication. Although many challenges remain, recent clinical success has generated intense interest in this therapeutic class.

The root of Aster tataricus L. f. (RA) has been widely used in the clinic for moistening lung, dispelling phlegm and relieving cough because of its significant therapeutic effects on respiratory diseases. In this study, a systematic data acquisition and mining strategy was established aimed at solving the complexity of the traditional Chinese medicine using ultra high performance liquid chromatography coupled with quadruple time of flight mass spectrometry (UHPLC-Q-TOF-MS). A total of 132 chemical constituents, including 43 terpenes, 31 flavonoids, 22 organic acids, 18 peptides, 9 coumarins, 3 steroids, 3 anthraquinones and 3 aldehydes were identified or tentatively characterized, among which 59 components were confirmed by comparison with the standard references. Meanwhile, the accurate mass measurements of the identified components were all with ±5 ppm error. Therefore, this work provided not only reliable data supports for the comprehensive analysis of the chemical constituents in RA, but also provided an efficient data acquisition and mining strategy to profile the chemical constituents for other traditional Chinese medicine complex system.

This study aimed to prepare an anti-metastatic diallyl trisulfide-exosome (DATS-Exo) drug delivery system. Exosomes in the supernatants of lung metastasis mouse melanoma B16BL6 cell line culture were extracted by ultracentrifugation. The quantity of exosomes was determined by transmission electron microscopy (TEM), Malvern particle size meter, and BCA assay. Expression levels of exosome-specific biomarkers CD9, TSG101, Flotillin 1 and lung organotropic biomarker α6 were detected by Western blot. The sonication method was used to load DATS into exosomes. The uptake of exosomes by B16BL6 cells and lung tissue was observed by laser confocal microscopy. Wound healing assay was used to evaluate the anti-migration effect of DATS-Exo in vitro. Experimental lung metastasis model was established to evaluate the anti-metastasis effect of DATS-Exo in vivo. Animal experiments have been approved by the Ethics Committee of Nanjing University of Chinese Medicine. The results showed that the particle size of DATS-Exo was 112.3 ±1.98 nm, polydispersity index (PDI) was 0.24 ±0.08, zeta potential was -24.33 ±4.11 mV, and the particles have classic tea tray-like membrane structure under TEM. The protein concentration of DATS-Exo was measured to be 1 312.33 ±6.27 μg·mL^-1. The drug loading rate was about 0.33% ±0.02%. The exosomes could be taken up by B16BL6 cells and the lung tissue. Compared with the free DATS group, DATS-Exo had a better inhibitory effect on tumor metastasis in vitro and in vivo. Taken together, these results indicate that exosomes derived from the lung metastasis tumor cells have lung organotropic characteristic and drug-loading properties. Using these kind of exosomes as carrier for anti-tumor drug delivery can be a novel and effective strategy of anti-metastatic therapy.

Fifteen flavonoids were isolated and identified by macroporous resin column chromatography, polyamide column chromatography, silica gel column chromatography, ODS column chromatography and preparative liquid chromatography from the ethanol extract Turpinia arguta. Their structures of these flavonoids were identified by NMR and mass spectrometry as argutoside F (1), luteolin-7-O-α-L-rhamanopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside (2), nuezhenoside (3), acacetin-7-O-α-L-rhamnopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside (4), apigenin (5), quercetin (6), quercetin-3-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside (7), rhoifolin (8), luteolin-7-O-α-L-rhamanopyranosyl-(1→2)-β-D-glucopyranoside (9), acacetin-7-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside (10), luteolin-7-O-β-D-glucopyranoside (11), luteolin (12), neodiosmin (13), apigenin-7-O-rutinoside (14), and quercetin-3-O-α-L-arabinopyranoside (15). Compound 1 is new, whereas compound 2, 7, 9, 13-15 were obtained from this plant for the first time.

Stroke is a common disease with complex and diverse clinical manifestations. Fufang Longmai Ningfang has been found to exhibit therapeutic effect on stroke, but its molecular mechanism for treating stroke remains unclear. The aim of this study was to investigate the molecular mechanism of Fufang Longmai Ningfang in the treatment of ischemic stroke by using the method of network pharmacology to define the active ingredients, target and molecular pathway of Fufang Longmai Ningfang. The TCMSP database was used to obtain the potential active components of Fufang Longmai Ningfang in the treatment of stroke. The CNKI database was used to verify the literature. The target was predicted and screened by PharmMapper and UniProt database. The target protein group was collected by TTD database. The Cytoscape software was used to construct a "component-target" network map, "component-target-disease" network map, and "target protein interaction" network map. The EAGLE algorithm was used for cluster analysis, the KEGG database was used for pathway analysis, and the SYBYL software was used for molecular docking for bioactivity verification. We found 39 potential active ingredients and 17 potential effective targets related to stroke. The representative active ingredients were ligustrazine, dioscin, and puerarin, and the related targets were MMP9, NOS3, NOS2, KDR, ALB, IL2, TGFB2, and CPB among others. The study found that carbon metabolism and HIF-1 signaling pathway are the main molecular pathways for treatment of stroke by Fufang Longmai Ningfang. The treatment of ischemic stroke by Fufang Longmai Ningfang may involve reduction of inflammatory response, enhancement of vascular permeability and inhibition of cerebral ischemia-reperfusion injury, providing a theoretical basis for their clinical use.

This study aimed to explore changes of gut microbiota in experimental model rats with psychological suboptimal health state (PSHS). The experimental rats were given a variety of stresses, including orphaned, uncertain empty bottle stress, circadian disorder and other stresses to simulate PSHS caused by various stress events in human life. Open field test, elevated cross maze, blood biochemical indexes and other auxiliary models were used to evaluate the experimental animal model. Changes of gut microbiota were studied by 16S rRNA gene high-throughput sequencing. All experimental protocols were approved by the Animal Ethics Committee of the Biomedical Research Laboratory of Shanxi University. Compared with the control group, the body weight of PSHS group gained slowly (P < 0.01). In addition, the numbers of crossings and rearings in the open field test, and the percentage of time and entries in the open arms, were significantly reduced compared to the control group (P < 0.05). But there were no significant change in the percentage of sucrose preference, blood biochemical, blood routine examination and so on. Gut microbiota analyses showed that the diversity of gut microbiota in PSHS model rats changed, and the relative abundances of 10 species of gut microbiota changed significantly (P < 0.05, P < 0.01), including Bacilli, Lactobacillales, Lactobacillaceae, Lactobacillus, Clostridia, Clostridiales, Blautia, Coriobacteriales, Coriobacteriaceae, and Adlercreutzia. To some extent, the established PSHS model rats reflect the state of humans with PSHS. By studying the changes of gut microbiota in the animal model with PSHS, this study provided an important reference for explaining the physiological change due to PSHS and formulating relevant measures of intervention.

This study aimed to investigate apoptosis induction of ginsenoside compound K (ginsenoside CK) in human liver cancer SMMC-7721 cells and the involvement of TGF-β1/Smads signaling pathway. MTT assay was used to detect cell viability following ginsenoside CK treatment in SMMC-7721 cells. Annexin V-FITC/PI assay was used to detect apoptosis. After ginsenoside CK, or TGF-β1/Smads pathway activator TGFβ1 and inhibitor LY2109761 treatment, the TGF-β1/Smads pathway proteins and apoptosis proteins were detected by Western blot. The results showed that ginsenoside CK inhibited the proliferation of SMMC-7721 cells in a dose-and time-dependent manner. Annexin V-FITC/PI showed that ginsenoside CK induced apoptosis in SMMC-7721 cells. Meanwhile, ginsenoside CK inhibited the expression of Smad2/3, p-Smad2/3, Smad4, but promoted Smad7 expression, cleavage of caspase-3 and down-regulated Bcl-2/Bax. Compared with TGFβ1 treatment alone, levels of Smad2/3, p-Smad2/3, Smad4 and the ratio of Bcl-2/Bax were down-regulated, whereas Smad7 or cleaved caspase-3 was up-regulated in the ginsenoside CK+TGF-β1 group. In addition, Smad2/3, p-Smad2/3 and Smad4 expression were decreased in LY2109761 group. Compared with LY2109761 group, cleaved caspase-3 expression and Bcl-2/Bax have no significant change in ginsenoside CK+LY2109761 group. Taken together, our results showed that ginsenoside CK induced apoptosis in SMMC-7721 cells, and such induction is related to inhibiting TGF-β1/Smads signaling pathway.

The size and surface morphology of carrier lactose had influence on the aerosolization performance of dry powder inhalers. In this article, chlorpheniramine maleate was blended with two types of commercial carrier lactose, which were Lactohale 100^® and Respitose SV003^® (SV003), as formulation model. In vitro experiments were conducted using fast screening impactor at 30 L·min^-1 and 60 L·min^-1 respectively. Meanwhile, computational fluid dynamics (CFD) coupling with discrete element modelling (DEM) was applied to discuss the movements of those two carrier particles in Handihaler^® at the flow rate mentioned above. The dispersion characteristics of two formulations and the dispersion mechanism of Handihaler^® were analyzed by establishing the relationship between in vitro experiments and numerical simulation. The results of in vitro experiments and CFD-DEM demonstrated that the aerosolization performance of formulation with SV003 was better. The linear correlation (R²=0.940 1) between fine particle dose and total energy loss by carrier collision within the wall of device was found by comparing the in vitro experimental results with CFD-DEM results. It revealed that particle-wall collision in Handihaler^® had direct impact on the dispersion results of formulation.

Five components in the impurity profile of tinidazole glucose injection were detected and identified by UPLC-Q Exactive quadrupole-electrostatic field orbitrap high resolution mass spectrometry, in combination with retention time references, organic reaction mechanisms and UV spectral analysis. They are 2-methyl-5-nitroimidazole (impurity 1), 5-hydroxymethylfurfural (impurity 2), 1-(2-(ethylsulfonyl)ethyl)-2-methyl-4-nitro-1H-Imidazole (impurity 5), 1-(2-(ethylthio)ethyl)-2-methyl-5-nitro-1H-imidazole (impurity 6) and 1, 4-di-N-oxo-2-methyl-5-nitro-1H-imidazole (impurity 8) respectively, of which impurities 6 and 8 are identified for the first time. These results and detection methods are useful for monitoring the manufacturing process and quality control of tinidazole and glucose injection solution.

The Chinese medicine injections prepared by the natural products containing sesquiterpenoids caused various adverse reactions in clinical use, among which skin allergic reactions are the most common. However, whether the reason of allergic reaction was related to the three isoprene units contained in the sesquiterpenoids is not clear, so the evaluation of drug safety has important guiding significance. The sesquiterpenoids are small molecular substances, and they are not antigens or haptens. They may induce anaphylaxis reactions by acting mast cells directly. Current research confirmed that Mas-related G protein-coupled receptor-X2 (MRGPRX2) which is a 7-transmembrane G protein coupled receptor on mast cells was a key target mediated allergic reactions induced by many small molecular drugs. Unlike IgE-mediated allergic reactions, pseudo-allergic reaction is related to dosage and dosing rate, and occurs in the first exposure to the sensitizer. In this paper, a series of experiments in vitro found that not all sesquiterpenoids caused anaphylactoid reactions. Ginsenoside Re, ginsenoside Rb1 and germacrone were selected as representative of sesquiterpenoids for calcium imaging assay. The data confirmed that only germacrone activated calcium mobilization through MRGPRX2, causing an increase in intracellular calcium ion concentration in mast cells. Furthermore, the release rate of β-hexosaminidase and the release amount of histamine analysis confirmed that germacrone induced mast cells degranulation directly. Knockdown of MRGPRX2 expression by siRNA and competitive binding experiments against ciprofloxacin were used to prove the target of germacrone was MRGPRX2. The results indicated that germacrone could activate mast cells directly to induce anaphylactoid reaction via MRGPRX2, which might be the reason of skin allergic reactions caused by injections containing germacrone.