The study was undertaken to clarify the differences in metabolite groups between Aster yunnanensis and Pulicaria insignis to establish plant origin and identify plant resources. Non-target metabolomics of A. yunnanensis and P. insignis was undertaken with sample derivatives and gas chromatography-mass spectrometry (GC-MS). Principal component analysis (PCA), partial least-squares discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to characterize the differing metabolites of A. yunnanensis and P. insignis. Correlation analysis of these metabolites and metabolic pathway analysis allowed us to identify metabolic pathway changes between samples. Characterization of the antibacterial activity of the essential oil from A. yunnanensis and P. insignis showed that 384 metabolites were identified in the two species, including amino acids and peptides, phenylpropanoids, aromatics, glycoside, nucleotide, flavonoid, alkaloids, saccharides, vitamin, organic acid, lipids, esters, alcohol. A total of 92 differential metabolites with significant differences in content (P < 0.05, VIP > 1) were identified. In conclusion, a new method based on pre-column derivatives and GC-MS metabolomics was used to distinguish and compare A. yunnanensis and P. insignis metabolites.

Hesperidin nanosuspensions (HDN-NS) were prepared with tea saponin (TS) as stabilizer. The feasibility of TS as a natural stabilizer and the mechanism of TS stabilized nanosuspensions were investigated to provide reference for the development of green nano-preparations of hesperidin. HDN-NS was prepared by high-speed shearing combined with high-pressure homogenization. Using average particle size and polydispersity index as evaluation indexes, the effects of drug concentration, shearing speed, shearing time, homogeneous pressure and homogeneous cycles on HDN-NS were investigated by single factor experiment. The results of single factor investigation were as follows: drug concentration was 8.0 mg·mL^-1, shearing speed was 16 000 r·min^-1, shearing time was 2 min, the homogeneous cycles were 6 cycles at 35 MPa and 12 cycles at 100 MPa. The pH, ionic strength, zeta potential and critical micelle concentration of TS were investigated to determine the role of electrostatic repulsion in the mechanism of TS stabilized nanosuspensions. The results showed that electrostatic repulsion is involved in the mechanism of TS stabilized HDN-NS. In conclusion, at low concentration, TS can significantly reduce the particle size of HDN-NS, which indicates that TS has the potential to stabilize nanosuspension. Electrostatic repulsion is one of the mechanisms of TS stabilizing nanosuspension.

The three polymorphs (Ⅰ, Ⅱ, Ⅲ) and one amorphous (Ⅳ) form of imatinib-oxalate new salt were prepared and characterized by powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis and infrared spectroscopy, and transformation rules among the four salts were analyzed. The solubility of polymorph Ⅱ was investigated by high performance liquid chromatography. The results show that polymorph Ⅱ was stable but polymorph Ⅰ, Ⅲ and amorphous Ⅳ were unstable at room temperature. Polymorph I transformed into polymorph Ⅱ at room temperature. At relative humidity 90%, polymorph Ⅰ, Ⅱ and amorphous Ⅳ transformed into polymorph Ⅲ, but polymorph Ⅲ transformed into amorphous Ⅳ at 70 ℃. The solubility of imatinib was significantly improved after being salted with oxalic acid, and the equilibrium solubility of polymorph Ⅱ in pH 6.8 buffer solution and pure water was increased by 4.1 and 21.2 fold, respectively, as compared to bulk drug. This research provides guidance for the development and quality control of a new salt form of imatinib.

The MIKC-type MADS-box gene family plays an important role in flower development in plants. This study identifies members of the MIKC-type gene family in Cannabis sativa L. at the genome level, with the chromosomal location and linkage, evolutionary relationships, and identification of conserved motifs determined using bioinformatics tools. The results show that C. sativa contains 39 members of the MIKC-type MADS-box gene family (named CsMADS1-CsMADS39) unevenly distributed on nine chromosomes. The encoded proteins range in length from 146 to 503 amino acids, and the theoretical isoelectric points range from 5.19 to 10.12. Molecular weights range from 16 739.35 to 57 070.56 Da. The subcellular location of CsMADS genes is mainly in the nucleus. The result of conserved domain analysis showed that all genes contain the MADS conserved domain. The analysis of GO showed that all genes were annotated to 331 GO terms, which were clustered by molecular function. A phylogenetic tree showed that CsMADS genes could be divided into 14 subclasses, according to ABCDE homologous gene model; CsMADS genes are clustered with SQUA/AP1, AP3, PI, GGM13, AG, SEP/AGL2 subfamilies in Arabidopsis. There are abundant cis-acting elements in the upstream promoter region of CsMADS genes, mainly light regulatory elements. The results of real-time fluorescent quantitative PCR showed that some CsMADS genes are highly expressed in flowers and bracts, with tissue-specific expression. This study identified and analyzed the MIKC-type MADS-box gene family in C. sativa at the genome level, and provides a theoretical basis for further exploration of the function of MIKC-type genes and their role in regulating the growth and development of medicinally important hemp.

Clarithromycin (CLA) belongs to the second generation macrolide antibiotic. The commercial crystal form of CLA is form Ⅱ, and it exhibits the poor compressibility during the tablet pressing process. Since the crystal form of drugs has a significant effect on their mechanical properties, from the perspective of crystallography, this study investigated the difference of the compressibility between CLA form Ⅰ and form Ⅱ, and analyzed the mechanism that led to such difference. On the other hand, from the perspective of pharmaceutics, we also studied the effect of filler on the compressibility of form Ⅱ. It was found that CLA form Ⅰ had improved plastic deformation than form Ⅱ because of the slip planes in its crystal structure leading to the better compressibility. Moreover, microcrystalline cellulose, pre-gelatinized starch and lactose monohydrate could improve the compressibility of form Ⅱ, and microcrystalline cellulose showed the best effect. We improve the compressibility of CLA from crystal form and filler, and also lay a foundation for the development of CLA solid preparations.

Pulmonary fibrosis (PF) is a chronic respiratory inflammation disease that threatens human health. The topical immune microenvironment of lung tissue regulates progression of fibrosis. In this study, the efficacy and molecular mechanism of suplatast tosilate (ST) against PF were observed. ST is a T helper 2 (Th2) cytokine inhibitor for clinical treatment of bronchial asthma. But whether it can be applied to therapy of chronic PF and the biomechanism of ST inhibiting Th2 cytokine release are not clear. Using in vivo and in vitro experiments, we found that ST can significantly suppress the pathogenesis of chronic PF induced by multiple bleomycin injury, improve the lung function, and decrease the deposition of collagen in lung tissue. In addition, ST decreases Th2 cytokine releasing through restraining Th2 cell differentiation in the meantime, but did not influence the T helper 1 (Th1) cell differentiation and Th1 cytokine releasing. Further studies showed that ST inhibits Th2 cell differentiation by down-regulating GATA-binding protein 3 (GATA3) expression and activity through inhibiting the phosphorylation of signal transducer and activator of transcription 5 (STAT5) and mammalian target of rapamycin (mTOR). The excessive expression of GATA3 in lungs can reverse the anti-PF effect of ST. All procedures involving animal treatment were approved according to the Committee on the Ethics of Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Our research not only clarifies the pharmacological mechanism of ST, but also provides a new selection for clinical anti-PF drug therapy.

Hepatic fibrosis is a common pathological link of multiple chronic liver diseases, and further causes cirrhosis and even liver cancer. Tibetan medicine possessed significant and unique clinical effects in the prevention and treatment of hepatic fibrosis through unique medication methods such as single prescription, time synergy, and dialectical combination prescription. Pharmacological experimental studies have shown that a variety of Tibetan medicine formulas and herbs have anti-fibrotic effects, and their main pharmacological action mechanism involves inhibiting lipid peroxidation, reducing liver stellate cell activation and proliferation, regulating collagen metabolism, etc. This review summarizes the research progress of the clinical application and pharmacodynamic mechanism of Tibetan medicine in the prevention and treatment of liver fibrosis, aiming to provide a reference for the development of clinical use and innovative drugs discovery of Tibetan medicine against hepatic fibrosis.

With the increasing drug resistance of bacteria, especially Gram-negative bacteria, the infection of drug-resistant bacteria has become one of the most challengeable clinical problems. The siderophore-antibiotic conjugates based on the "Trojan horse" strategy can penetrate the extracellular membrane of Gram-negative bacteria by active transport, and they are expected to become a powerful weapon for clinical anti-infection treatment. This review describes the drug design strategies of siderophore-antibiotic conjugates reported in recent years, and focuses on the use of different types of antibiotics in this strategy.

Liver fibrosis is a common scarring response to virtually all forms of chronic liver injury and is characterized by excessive accumulation of extracellular matrix. Excessive activation of hepatic stellate cells (HSCs) is a key step in liver fibrogenesis. The withanolide extract of Physalis angulata (WEP) is a physalin-type withanolide enriched partition from Physalis angulata. In this study, liver fibrosis mice models were established by CCl₄ and bile duct ligation (BDL) in vivo. Transforming growth factor-β1 (TGF-β1) was given in vitro to induce activation of human hepatic stellate cells LX-2 and treated with WEP at different concentrations. All animal experiments in this paper have been approved by the Ethics Committee of China Pharmaceutical University. The in vivo results showed that, compared with the CCl₄ or BDL group, WEP could reduce collagen deposition and liver damage, and reduce the levels of aspartate transaminase (AST) and alanine transaminase (ALT) in serum. In vitro, WEP had no significant cytotoxicity to LX-2 cells, but significantly reduced the mRNA and protein expressions of fibrotic markers collagen type Ⅰ α 1 chain (COL1A1) and α-smooth muscle actin (α-SMA) and inhibited the activation of hepatic stellate cells. In addition, WEP inhibited the expression of yes-associated protein (YAP) and the phosphorylation level of Smad family member 2 (Smad2) in vivo and in vitro. In conclusion, WEP can inhibit hepatic stellate cells activation via regulating the YAP and TGF-β-Smad pathways, and shows promising anti-fibrosis activity in vitro and in vivo.

We investigated the therapeutic effect and mechanism of isoforskolin on bleomycin-induced pulmonary fibrosis in mice. The animal welfare and experimental process were in accordance with the Regulations of Animal Ethics Committee of Kunming Medical University. Male Kunming mice were randomly divided into five groups: sham operation group (intratracheal instillation of normal saline), bleomycin group (intratracheal instillation of bleomycin 5 mg·kg^-1), positive drug control group (intratracheal instillation of bleomycin 5 mg·kg^-1 + intraperitoneal injection of dexamethasone sodium phosphate 2.5 mg·kg^-1), isoforskolin (2.5 and 10 mg·kg^-1) groups (intratracheal instillation of bleomycin 5 mg·kg^-1 + intragastric administration of isoforskolin 2.5 and 10 mg·kg^-1). The method of drug administration was once a day for 28 days. On the 7^th and 28^th day of the experiment, the mice were killed, and the lung tissue and bronchoalveolar lavage fluid samples were collected. Hematoxylin eosin (H & E) staining and Masson staining were used to detect the pathological changes of lung tissue. The content of hydroxyproline in lung tissue was detected by alkaline hydrolysis method. The levels of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) in bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay (ELISA). The expressions of transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) in lung tissue were detected by Western blot. The experimental results showed that compared with the bleomycin group, the degree of inflammation and fibrosis in the lung tissue of mice in 10 mg·kg^-1 isoforskolin group was significantly reduced, the content of hydroxyproline in the lung tissue was decreased, the levels of TNF-α and IL-1β in BALF were decreased, and the protein expressions of TGF-β1 and CTGF in the lung tissue were downregulated, the differences were statistically significant (P < 0.05). The results suggest that isoforskolin can inhibit the release of inflammatory cytokines TNF-α and IL-1β, downregulate the protein expression of profibrotic factors TGF-β1 and CTGF, and exert anti pulmonary fibrosis effect through both anti-inflammatory and anti fibrotic effect.