Growth differentiation factor 15 (GDF15) is an endocrine hormone that belongs to the transforming growth factor β (TGFβ) superfamily, which plays a role by binding to the glial cell line derived neurotrophic factor (GDNF)-family receptor α-like (GFRAL)-rearranged during transfection (RET) heterodimer receptor. A number of studies have confirmed that GDF15, as a biomarker for obesity, diabetes, tumors, non-alcoholic fatty liver disease, ischemic diseases, and so on, has become a new target for new drug discovery. At present, pharmaceutical companies around the world are carrying out drug discovery with GDF15 as a new therapeutic target involving many therapeutic areas such as anti-obesity, anti-tumor, and treatment of anorexia syndrome. Comprehensive analysis of the advantages and disadvantages of the GDF15 target, discussion, and objective evaluation of research and development of new drugs based on GDF15 will provide a scientific basis for the discovery of innovative drugs that could relieve the human suffering from illness.

Protein disulfide isomerase (PDI), also named PDIA1, is an archetype member of protein disulfide isomerase family, which mainly exists in endoplasmic reticulum and plays an important role in pathophysiological progress via enzyme activity and molecular chaperone function helping protein folding correctly. Amyotrophic lateral sclerosis (ALS) is a kind of neurodegenerative diseases characterized by abnormal protein aggregation. Recently, PDI mutants have been found in ALS patients and the important role of PDI protein in the development of ALS has also been confirmed. Here, we focus on the recent studies of PDI in ALS hoping to provide a novel target for the treatment of ALS.

Bacterial pneumonia is a common clinical disease and the abuse of antibacterial leads to the production and prevalence of resistant bacteria. Novel antibacterial active ingredients can be found from natural products for the treatment of bacterial pneumonia. Pulmonary delivery systems can directly deliver drugs to infected lung tissues, favoring the treatment of bacterial pneumonia. Cinnamon oil (CO) is a volatile oil extracted from cinnamon, which has antibacterial and anti-inflammation functions. However, the preparation of its pulmonary delivery systems is difficult because of its oil and volatile properties. Here, CO-β-cyclodextrin inclusion complex (CO-β-CD) was prepared. Its dry powder inhalers (DPIs) were obtained by lyophilization. The DPIs had the aerodynamic diameter of 1.34 μm and the fine particle fraction (FPF) of 30.90%, which was suitable for pulmonary delivery. The minimal bactericidal concentration of CO-β-CD was 2 mg·mL^-1 against Staphylococcus aureus (SA). The animal experiments were approved by the Ethics Committee of Academy of Military Medical Sciences and the experiments were conducted in accordance with relevant guidelines and regulations. A high intratracheal (i.t.) dose (100 mg·kg^-1) of CO-β-CD did not show significant toxicity to the mice. Bacterial pneumonia mice models were established after intraperitoneal injection of dexamethasone and then i.t. administration of SA. CO-β-CD and penicillin were separately i.t. administered to the mice. Both of them alleviated the lung injury of mice and remarkably increased the survival rates. Compared to penicillin, CO-β-CD significantly reduced the infiltration of inflammatory cells and the numbers of leukocytes and neutrophils in the blood, and the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the lung tissues were similar to those of the healthy mice, indicating that CO-β-CD had the capability of anti-inflammation besides antibacterial effect in vivo. CO-β-CD dry powder inhalers are a potential pulmonary delivery system for the treatment of bacterial pneumonia.

Pulmonary drug delivery agents deliver drugs directly to the lung tissue to obtain higher local concentration, which is beneficial to the treatment of lung diseases, and may reduce the systemic side effects. Therefore, it has become the preferred drug for the treatment of many lung diseases. However, the drugs entering the lungs are easily cleared by the lung tissues, which reduce the retention time of the drugs in the lungs and affects the efficacy. Although particles with a smaller particle size (1-5 µm) are easily inhaled into the lungs, they are also easily swallowed and cleared by lung macrophages. While the porous polymer microspheres (PPMS) with larger geometric diameter (Dg > 5 µm) and low density (ρ < 0.4 g·cm^-3) can not only effectively avoid the phagocytosis of alveolar macrophages, but also have a high effective deposition rate in the lungs due to the appropriate aerodynamic diameter, moreover, the polymer is biodegradable and non-toxic, so it has become a research hotspot for pulmonary drug delivery carriers. This article combined with the lung clearance mechanism of granules, summarized the preparation materials and methods of PPMS, as well as its quality control, etc. Furthermore, opinions are also put forward for the development of PPMS, to provide a reference for the in-depth study of PPMS.

Most small molecule drugs bind to enzymes, receptors or ion channels, which possess binding pocket for drug occupation. However, the study of drugs that interfere with protein-protein interactions has always been a challenging subject. The discovery of molecular glues and degraders has opened an avenue to tackle this issue. With the structural features of bifunctional ligand molecular glues mediate the recognition and binding of two proteins. As a useful tool for chemical biology molecular glue can not only help to find probes to undruggable targets, but also can be developed into drugs through structure optimization in medicinal chemistry. This minireview concisely describes the features of molecular glue using a few existing drugs or active compounds.

This article systematically reviews the background and regulatory requirements of bioequivalence of orally inhaled and nasal drug products (OINDPs), as well as the basic regulatory requirements for the assessment by the guidelines and guidance issued in China, the United States, and the European Union. Detailed statistical evaluation method considerations and calculations of the US FDA population bioequivalence (PBE) method were presented for the evaluation of in vitro bioequivalence (IVBE) for OINDPs. Using the example described in the FDA Draft Guidance for budesonide inhalation suspension, the PBE analysis statistical parameters were calculated via the R programming, and the results were compared with that in the guidelines. Moreover, pseudo-code for the PBE calculation program was provided. This paper aims to provide guidance and references for the research and development of new drug, as well as pharmaceutical quality control, and development of generic medicinal products for OINDPs.

The structural modification of natural product represents a powerful tool for anti-cancer drug discovery. Noscapine, as a phthalideisoquinoline alkaloid from opium, has been used as an over-the-counter antitussive drug with excellent oral bioavailability and low toxicity. Recently, the potential of this compound as a particularly attractive lead for anti-cancer drug discovery has been demonstrated. Multiple mechanisms, especially the interference of tubulin polymerization, might be involved. Thereafter, various structural modifications based on semisynthetic routes, which aims to improve the anti-cancer activity and pharmacokinetic properties, as well as to probe the mechanism, has been performed. Several analogues are emerging as possible candidates as novel anticancer therapies. This perspective mainly discusses the advancing noscapine and related analogues in the fight against malignant disease in recent years. Furthermore, the future directions of this evolving field were also preliminary prospected.

An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous determination of seven components (chlorogenic acid, rutin, narirutin, hesperidin, sinensetin, nobiletin, tangeretin) in Citri Exocarpium Rubrum. The separation was performed over 12.0 min on a Shim-pack GIST C18 column (100 mm×2.1 mm, 2.0 μm) with a mobile phase consisting of acetonitrile (A) and 0.1% formic acid water solution (B) with gradient elution at a flow rate of 0.4 mL·min^-1; the column temperature was 30℃ and the injection volume was 1 μL. Detection was performed on a QTRAP 4500 mass spectrometer equipped with electrospray ionization. Positive and negative electrospray ionization was performed in multiple reaction monitoring mode. All of the analytes showed good linearity (r ≥ 0.997 3) in the tested ranges, with good precision, repeatability and stability for all analytes. The average recoveries were in the range of 99.32%-107.75% with relative standard deviations RSD ≤ 3.94%. The established method is accurate, stable and reproducible, and can provide a research method for the quality control of Citri Exocarpium Rubrum.

Type 2 diabetes is a common form of diabetes and can have serious consequences for diabetics when their wounds do not heal properly due to impaired function. Glycosaminoglycans (GAGs) are widely found in skin tissue. Due to the isomerization of C6 in uronic acid and different sulfuric acid substitutions, the structure of GAGs is relatively complex. The fine structure of GAGs in the skin of diabetic patients has not been studied. In this study, the structure of GAGs in the skin of streptozotocin (STZ)-induced diabetic mice was characterized by liquid chromatographytandem mass spectrometry (LC-MS/MS). All animal experiments were carried out with approval of the Animal Ethics Committee of Ocean University of China. The results indicate that the content of hyaluronic acid (HA) in STZ-induced diabetic mouse skin was significantly lower than that of non-diabetic mice. Although there was no significant difference in the content of chondroitin sulfate (CS) and heparin sulfate (HS) between diabetic mouse and normal mouse skin, the disaccharide compositions were different. The expression of CS-4S6S, HS-0S, HS-NS, and HS-6S in STZ-induced diabetic mouse skin was higher than in non-diabetic mice. While the content of HS-NS6S was lower. In addition, the degree of sulfation of HS in STZ-induced mouse skin was lower than that of normal mouse skin. These results provide a basis for the pathogenesis of diabetes and the development of wound healing dressings for diabetic patients.

In recent years, the prevalence of non-alcoholic fatty liver disease (NAFLD) has been dramatically increased in China and specific targeted therapy is still unavailable. The purpose of this research was to investigate whether schisandrin B (SchB) improves NAFLD and the potential mechanisms. Wildtype mice with C57BL/6J background were treated with special high fat diet (containing 40% fat, 22% fructose, 10% sucrose, and 2% cholesterol) for 16 weeks to induce NAFLD. Then SchB (120 mg·kg^-1) were used to treat NAFLD mice for 6 weeks. Body weight, food intake, glucose tolerance, insulin resistance, serum level of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assayed and histopathological analysis were performed to evaluate the improvement of NAFLD induced by SchB. Furthermore, the level of lipopolysaccharide (LPS) in serum, intestinal permeability, and the expression of genes and proteins associated with mucosal defense were evaluated, intestinal flora composition in fresh cecal contents were analyzed and differential flora were identified to explore the potential mechanism. All animal experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. These results showed that SchB significantly reduced the body weight of NAFLD mice without changing food intake, and effectively reduced serum level of TC, ALT, and AST. SchB also significantly altered the composition of the microflora in NAFLD mice, increased the abundance of the Akkermansia muciniphila (A. Muciniphila) and elevated the expression of genes and proteins associated with the mucosal defense in ileum and colon, restored the permeability of intestinal barrier. In summary, SchB improves NAFLD by regulating the composition of the microflora and enhancing the function of intestinal barrier to further reduce the excessive lipids accumulation and hepatic inflammation.