Cancer cells can be distinguished from normal cells by displaying aberrant levels and types of carbohydrate structures on their surfaces. These carbohydrate structures are known as tumor-associated carbohydrate antigens (TACAs). TACAs were considered as promising targets for the design of anticancer vaccines. Unfortunately, carbohydrates alone can only evoke poor immunogenicity because they are unable to induce T-cell-dependent immune responses, which is critical for cancer therapy. Moreover, immunotolerance and immunosuppression are easily induced by using natural occurring TACAs as antigens due to their endogenous property. This review summarizes the recent strategies to overcome these obstacles: (1) covalently coupling TACAs to proper carriers to improve immunogenicity, including clustered or multivalent conjugate vaccines, (2) coupling TACAs to T-cell peptide epitopes or the built-in adjuvant to form multicomponent glycoconjugate vaccines, and (3) developing vaccines based on chemically modified TACAs, which is combined with metabolic engineering of cancer cells.

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Research and development of isoform selective JAK inhibitors has become a hot topic in this field. With the assistance of high throughput screening and rational drug design, more and more JAK inhibitors with improved selective profiles will be discovered as biological probes and even therapeutic agents.

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Background/Aims: Histone acetylation has been demonstrated to be associated with inflammation response. Histone acetyltransferase (HAT) Mof, specifically acetylating lysine 16 of histone H4 (H4K16), has been reported to regulate T cell differentiation. In addition, it has been suggested that acetylation of H4K16 is associated with the inflammatory response. We evaluated the role and potential mechanism of Mof in the development of experimental colitis. Methods: We used Mof conditional knockout mice to study the role of Mof in dextran sulfate sodium (DSS)-induced colitis and detected the differential expression of genes due to Mof deficiency involved in the inflammatory response, particularly the Th17 signaling pathway, by western blotting, quantitative PCR and RNA sequencing (RNA-seq). Results: A significant elevation of Mof was observed in colonic tissues of mice with DSS-induced colitis. Mof deficiency alleviated the severity of DSS- induced colitis in mice. We found that Th17 signaling pathway associated genes, including Il17a, Il22, RORγt, RORα, Stat3, TGF-β 1, and Il6, were downregulated in colon tissues with Mof deficiency. RNA-seq data analysis suggested that 68 genes were related to inflammatory response processing and 47 genes were downregulated in Mof defective colon tissues. Conclusion: Our study demonstrated that HAT Mof is involved in the development of colitis, and the lack of Mof ameliorates DSS-induced colitis in mice.

Itch, the unpleasant sensation that evokes a desire to scratch, accompanies numerous skin and nervous system disorders. However, the molecular mechanisms of itch are unclear. Acid-sensing ion channel 3 (ASIC3) is a sensor of acidic and primary inflammatory pain. The whole-cell patch clamp technique was used to determine the effect of chloroquine (CQ) on ASICs currents in primary sensory neurons or the Chinese hamster ovary cells transfected with rat ASIC1a or ASIC3. Site-directed mutagenesis of plasmid was performed. Scratching behavior was evaluated by measuring the number of bouts during 30 min after injection. CQ, an anti-malarial drug defined as a histamine-independent pruritogen, selectively enhanced the sustained phase of ASIC3 current in a concentration-dependent manner either in ASIC3-transfected Chinese hamster ovary cells or in primary cultured rat dorsal root ganglion neurons. Further studies revealed that the effect of CQ on ASIC3 channels depends on the newly identified non-proton ligand-sensing domain. Importantly, CQ-evoked scratching behavior was largely alleviated by APETx2, a selective ASIC3 channel blocker. Like CQ, other compounds such as amiloride, 2-guanidine-4-methylquinazoline and neuropeptide FF, which have been previously reported to be non-proton ligands that activate ASIC3, undoubtedly evoked the scratching response. In conclusion, ASIC3, a proton-gated ion channel critical for pain sensation, also functions as an essential component of itch transduction.

In recent years, the development and applications of protein drugs have attracted extensive attention from researchers. However, the shortcomings of protein drugs also limit their further development. Therefore, bioactive peptides isolated or simulated from protein polymers have broad application prospects in food, medicine, biotechnology, and other industries. Such peptides have a molecular weight distribution between 180 and 1000 Da. As a small molecule substance, bioactive peptide is usually degraded by various enzymes in the organism and have a short half-life. At the same time, such substances have poor stability and are difficult to produce and store. Therefore, these active peptides may be modified through phosphorylation, glycosylation, and acylation. Compared with other protein drugs, the modified active peptides are more easily absorbed by the body, have longer half-life, stronger targeting, and fewer side effects in addition to higher bioavailability. In the light of their functions, bioactive peptide can be divided into antimicrobial, anti-tumour, anti-angiogenic, antioxidant, anti-fatigue, and anti-hypertensive peptides. This article mainly focuses on the introduction of several promising biologically active peptides functioning as antimicrobial, anti-tumour, antiangiogenic, and antioxidant peptides from the three aspects modification, structural characteristics and mechanism of action.

This study was designed to investigate the pharmacokinetics of an innovative film-coated warfarin sodium tablet and to compare it with the marketed sugar-coated warfarin sodium tablet in humans. A single-dose, open-label, randomized, two-way crossover study was performed in 24 healthy Chinese male volunteers. They were administered 2.5 mg of innovative film-coated warfarin sodium tablets or the marketed sugar-coated warfarin sodium tablets. Blood samples were collected at different time points after dosing for investigation of the pharmacokinetics of warfarin in human plasma. A sensitive liquid chromatography mass spectrometry method was established to determine warfarin in plasma. Drug and Statistics 2.1.1 was applied to calculate the pharmacokinetics parameters. The main pharmacokinetic parameters for film-coated and sugar-coated warfarin were the following: t , 103.5 ± 18.8 and 105.8 ± 21.3 hours; T , 0.7 ± 0.5 and 1.3 ± 0.8 hours; C , 347.8 ± 74.8 and 322.9 ± 75.7 ng/mL; AUC , 16,024.2 ± 3713.9 and 15,586.6 ± 3477.0 ng·mL ·h; AUC , 17,335.7 ± 4089.1 and 16,912.0 ± 3911.2 ng·mL ·h, respectively. The human pharmacokinetics of film-coated and sugar-coated warfarin were slightly different. The oral absorption and bioavailability of innovative film-coated warfarin were slightly higher than those of the sugar-coated warfarin. This study is vital to clinical usage of warfarin not only because of the pharmacokinetic parameters of the 2 pharmaceutical dosage forms of warfarin but also to obtain data on the prevalence of CYP2C9 and VKORC1 genes and their influence on the concentration of warfarin.