Zedoary turmeric oil dry powder inhalers (ZDPIs) and curcumol dry powder inhalers (CDPIs) were prepared and intratracheally (i.t.) administered to the rats that suffered from acute lung injury (ALI) induced by lipopolysaccharide (LPS), and their therapeutic efficiencies were compared. Zedoary turmeric oil nanoemulsions and curcumol nanoemulsions were separately prepared and ZDPIs and CDPIs were obtained after the emulsions were added with 5% mannitol and lyophilized. ZDPIs and CDPIs are loose white powders with the aerodynamic diameters (D_a) of 3.02 and 2.67 µm, respectively. Both ZDPIs and CDPIs were suitable for pulmonary delivery. Animal experiments were approved by the Ethics Committee of Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences and the experiments were conducted in accordance with relevant guidelines and regulations. ALI rat models were established by i.t. administration of 0.2 mL of 5 mg·mL^-1 LPS solution and ZDPIs (with zedoary turmeric oil 0.5 mg) or CDPIs (with curcumol 0.5 mg) were i.t. administered. Both of them remarkably alleviated bleeding of injured lung tissues, and great reduced the levels of inflammatory factors tumor necrosis factor-α, interleukin-6, total proteins in the lung tissues (P < 0.001). They showed similar high effect against ALI. The non-curcumol components in zedoary turmeric oils could also have anti-inflammatory effect. ZDPIs and CDPIs are promising medications for the treatment of ALI and this comparative study is a paradigm of the research on active ingredients and effective compounds in natural products.

Intestinal Peyer's patches (PPs) are important sites to induce mucosal immunity response. As a kind of specialized epithelial cells in PPs, microfold cells (M cells) have a unique ability to take up antigens and can promote systemic immune response by transferring antigens to dendritic cells (DCs) in PPs. Selecting a suitable drug delivery vehicle and modifying the vehicle with a specific ligand can target drugs and bioactive substances to M cells to exert a therapeutic effect on intestinal immune-related diseases. This paper reviews the relevant literatures in the past 20 years, and summarizes and analyzes the ligands, types of vehicles, material properties that target M cells and main factors affecting the uptake of M cells, in order to provide construction ideas and experimental methods that can be worthy of reference for the study of PPs M cells-targeting drug delivery strategies.

Degradation of dexamethasone (DXM) is inevitable in the release test of dexamethasone implants (DI). In the release test conducted with flow-through cell method, the measured release curves of DI started to fall when cumulative release reached 70%-80%. Studies have shown that DI demonstrates a zero-order release rate of drug within every sampling interval, and a zero-order rate degradation in water (containing 0.05 mg·mL^-1 benzalkonium chloride). Hence, this study establishes a double zero-order model (DZOM) to calculate the release during sampling intervals with the formula R_i = [R_im-R_(i-1)m×(C_in/C_i0)]×2/(1+C_in/C_i0). At each sampling interval, we measure the initial and final drug contents in the release medium, and the concentrations of the active pharmaceutical ingredient (API) in the release medium obtained at the same condition of release test, to calculate the total released DXM from the implants including the degraded drug. This paper has also analyzed the reasons for the fluctuations in the drug release curve and the errors in the DZOM and provided solutions. Experimental results show that the DZOM has effectively solved the problems encountered in the normal release method (NRM). The DZOM can be a potential solution to drug degradation problems in the release tests of long-acting injections.

Delivering water-soluble drugs via carriers often causes problems such as low loading and rapid releasing, so it is an urgent need to construct a high-load sustained-release drug delivery system for the clinical application of water-soluble drugs. Two-dimensional layered nanomaterials exhibit great potential in drug delivery due to their high specific surface area. In this study, bulk graphitic carbon nitride (b-g-C₃N₄) was obtained by calcination of urea. Graphitic carbon nitride nanosheets (g-C₃N₄-NS) were made from an alkali chemical-ultrasonic-assisted stripping process. Scanning electron microscopy, transmission electron microscopy and atomic force microscopy were adopted to observe the morphological characteristics of g-C₃N₄-NS, while the structural characteristics of g-C₃N₄-NS were analyzed by X-ray diffractometer and Fourier transform infrared spectroscopy. Ultraviolet spectrometry and fluorescence spectrometry were used to investigate the optical properties of g-C₃N₄-NS, and scanning electron microscopy and X-ray diffractometer were employed to investigate the stability of g-C₃N₄-NS. Polyethyleneimine (PEI) was applied in the study to functionally modify g-C₃N₄-NS, and salvianolic acid B (Sal B) was used as a water-soluble drug model to investigate the loading capacity and drug releasing behavior of g-C₃N₄-NS. The results showed that g-C₃N₄-NS had a sheet structure, and it is easy to self-assemble in layers in the ionic environment to create flocculating settling. PEI modification can lead to the switching in the surface charge of g-C₃N₄-NS and significantly improve its stability. The results of cytotoxicity test and zebrafish embryo toxicity test showed that the toxicity was low when the concentration of PEI-g-C₃N₄-NS was less than 800 μg·mL^-1. The large specific surface area and surface charge of PEI-g-C₃N₄-NS allow the maximum load factor over Sal B to reach 327.4%. In addition, PEI-g-C₃N₄-NS can continuously release drugs slowly, with a cumulative release rate of 79.2% in seven straight days. The release process conforms to the Higuchi equation. In summary, g-C₃N₄-NS modified by PEI exhibits good biocompatibility and high stability, and shows great potential in high-load and sustained-release applications of water-soluble drugs.

Fifteen 9-substituted palmatine (1) derivatives were synthesized and evaluated for their anti-Helicobacter pylori (Hp) activities in vitro. Structure-activity relationship studies revealed that introducing appropriate substituted secondary amino group at position 9 of lead 1 might be beneficial for potency. Among them, compound 5a showed the most potential activity against metronidazole (Met) resistant Hp isolates with minimal inhibitory concentrations (MICs) of 4 μg·mL^-1, much better than that of lead 1. Compound 5a displayed satisfactory safety profile in acute toxicity assay. Molecular docking suggested that 5a might act on Hp urease. The results provided key scientific evidence for the development of 1 derivatives into a new class of anti-Hp component.

In this study, we used molecular docking technology and validation experiments in vitro to screen the active ingredients of Erzhi pill for treating osteoporosis. Firstly, the compound in Erzhi pill was docked with ten osteoporosis-related targets by molecular docking technology, and the five active compounds, salidroside, specnuezhenide, tyrosol, quercetin, and wedelolactone, were initially selected. Then, MC3T3-E1 osteoblasts were cultured in α-Mem medium containing different concentrations of compounds, and the cell proliferation rate and mineralized nodules were tested. The verification results showed that the proliferation of MC3T3-E1 cells with salidroside, specnuezhenide and quercetin were more obvious, and salidroside has a better effect on the mineralization of MC3T3-E1 cells than those of specnuezhenide and tyrosol. The molecular docking technology coupled with validation experiment in vitro can be used for the screening of anti-osteoporotic active ingredients of Erzhi pill, and it can also provide a method for the study of effective ingredients of traditional Chinese medicine.

Fc region of a monoclonal antibody usually contains two N-glycosylation, which have a profound influence on its structure and function. Here, we review the relationship between various glycoforms and their impact on structure and function of monoclonal antibodies, along with the technologies for glycosylation analysis. In addition, some related Chemistry, Manufacturing and Controls (CMC) regulatory considerations are also discussed, such as specification improvement, biosimilarity assessment as well as comparability of pre- and post-process changes in glycosylation.

Our previous report demonstrated puerarin protected β cells by up-regulating the expression of glucagon-like peptide-1 (GLP-1) receptor (GLP-1R). However, whether the anti-diabetic effects of puerarin in vivo depend on GLP-1R activation has not been clarified. In this study, the GLP-1R agonist exendin-4 (Ex4) and the GLP-1R antagonist exendin 9-39 (Ex9-30) were used. Type 2 diabetes was induced in C57BL/6J mice by a high fat diet (HFD) and divided into the following groups: control, HFD, HFD/puerarin (300 mg·kg^-1·d^-1), HFD/puerarin/exendin 9-39 (Ex9-39: 10 nmol·kg^-1·d^-1), and HFD/puerarin/exendin-4 group (Ex4: 10 nmol·kg^-1·d^-1). Animal experiments were approved by the Research Animal Care Committee of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine (AEWC-025). Puerarin was administered orally, Ex9-39 and Ex4 were administered by intraperitoneal injection for 10 days. Compared with HFD group, after 10-day treatment, the fasting blood glucose and oral glucose tolerance test (OGTT) of diabetic mice were effectively improved by puerarin (P < 0.05). Meanwhile, serum insulin levels were increased by puerarin, and levels of glucagon, triglycerides, and total cholesterol were significantly reduced (P < 0.05). Importantly, Ex4 significantly enhanced the anti-diabetic effects of puerarin in HFD mice, while Ex9-39 markedly inhibited the effects of puerarin (P < 0.05), which indicates that the effects of puerarin depend on GLP-1R activation. Furthermore, results of Western blotting of liver tissue showed puerarin effectively activated AKT and inhibited FOXO1, which relied on GLP-1R activation as well. Taken together, our findings demonstrate that puerarin ameliorates glucose homeostasis in HFD mice and is dependent on GLP-1R activation. This study provides experimental support for the potential application of puerarin.

The quality of the same herbal medicines in different daodi-origins in China is significantly different. Our research team previously found that using protocatechuic acid as a chemical marker can divide the Cynomorium songaricum into outside-the Great Wall (Inner Mongolia) and inside-the Great Wall (Gansu). However, the ecological mechanism that causes the quality variation of C. songaricum is unclear. Based on the microbiome-ecological strategy, 16s amplicon sequencing was performed on rhizosphere soils of C. songaricum in two origins (Inner Mongolia and Gansu), and the composition of soil microbial communities was analyzed. Tax4Fun was used to predict the metabolic function of soil microbial communities. Correlation analysis by combing with the abundance of key microbial community and ecological climate factors was performed. Microbiome sequencing results revealed that the diversity of soil microbial communities in Inner Mongolia was significantly higher than that in Gansu. Five core microbiomes (Arthrobacter, Streptomyces, Bacillus, etc.) and six specific biomarkers of soil microbial communities (Microbulbifer, Methyloceanibacter, Cynomorium_coccineum, etc.) which could be distinguished from two origins were identified. For the first time, metabolic function prediction showed the metabolic function profile of soil microbiome of C. songaricum in two origins. Redundancy analysis and correlation analysis results showed that the annual sunshine hours was the main ecological factor affecting the composition of the soil microbial community of C. songaricum, and it was extremely significantly negatively related to Streptomyces and Bacillus. This article provides a new idea for explaining the formation mechanism of quality variation in the daodi-origins of C. songaricum, and also provides a scientific basis for theoretical research on the quality ecology of herbal medicines.

The structural modification of nano-micellar polymer carriers can not only increase the solubilization of insoluble drugs, but also make drug-loaded carriers aggregate in tumor tissues. In this paper, paclitaxel (PTX) was used as a model drug, D-α-tocopherol polyethyleneglycol 1 000 succinate (TPGS) modified by disulfide bond (-S-S-) and oleic acid (OA) was synthesized and mixed micelles were prepared with different molar ratios of sodium deoxycholate (NADC), and TPGS and NADC mixed micelles modified by thioether bond were synthesized for comparative study. The effects of the critical micelle concentration (CMC) of the modified polymer and the molar ratio of TPGS-OA and NADC on the physical and chemical properties of the micelle were investigated. Finally, the redox drug release ability of disulfide bond and thioether bond was compared. The results showed that when the molar ratio of TPGS-OA to NADC decreased, the drug loading increased, but the stability decreased. When the molar ratio was 3:1, the particle size, potential and entrapment efficiency of TPGS-S-S-OA/NADC were 96.24 ±0.14 nm, -24.4 mV and (98.7 ±0.08)%, respectively, hemolysis rate of mixed micelles is less than 2%. The disulfide modified mixed micelles released PTX completely within 5 h in 10 mmol·L^-1 H₂O₂ environment (pH 7.4), which was similar to that of thioether modified micelles. It was also found that the stability of micelles decreased when the pH value was low. All animal experiments were in accordance with ethical standards and were approved by the Animal Experimental Center of Shenyang Pharmaceutical University (No.211002300032403). In this study, we mainly developed stable nano-micelle carriers which can target drug release in tumor heterogeneous environment.