Bile acids (BAs) are increasingly being appreciated as signaling molecules. Studies have shown that BAs regulate glucose and lipid metabolism mainly through the intracellular nuclear receptor farnesoid X receptor (FXR) and the transmembrane G protein-coupled receptor 5 (TGR5). FXR and TGR5 are highly expressed in the intestine. This article summarizes the synthesis, circulation, and regulation of BAs, as well as the effects of BAs on glycolipid metabolism through activation of liver FXR and inhibition or activation of intestinal FXR and TGR5. Furthermore, we illustrate the molecular mechanism of BAs on glycolipid metabolism by the relevant signaling pathways, including small heterodimer partner (SHP), fibroblast growth factor 15/19 (FGF15/19), ceramide and glucagon like peptide-1 (GLP-1). This review may serve as a reference for basic and clinical studies.

Medicinally active molecules are those that have pharmacological effects. Research on protein targets of these molecules not only clarifies their mechanism of action, but also deepens our understanding of biological systems. Here we review recent advances in protein targets of drugs used in clinical practice or in preclinical research. They have various functions including anti-inflammatory, anti-malarial, anti-tumor and other biological activities. Activity-based protein profiling (ABPP) and cellular thermal shift assay (CETSA) are two useful methods to identify the protein targets of small molecules. ABPP depends on a derivative active molecule probe to pull down the protein targets to reveal the interaction mechanisms between the active molecules and targets. Drug target engagement also can be assessed by means of CETSA based on ligand-induced changes in protein thermal stability. In the CETSA approach, the active molecules do not need to be chemically modified. Combining the CETSA method with quantitative mass spectrometry is an effective approach to study the effect of compounds on the thermal profile of a cellular proteome and identify the protein targets.ABPP and CETSAcan be complementary and effectively clarify the protein targets. The study of protein targets will help reveal the mechanism of action of medicinal molecules, reveal toxic mechanisms and aid in the discovery of new medicinal targets to promote the process of drug development.

Vascular endothelial cells play a major role in maintaining the oxygen and nutrient supply to all tissues in the body. Endothelial cells, together with vascular endothelial growth factor, are also the driving forces of tumor angiogenesis, a process describing the growth of blood vessels from the existing vasculature in tumor tissues. Reprogramming of endothelial cell metabolism satisfied the needs for biomass and energy in the process of tumor angiogenesis, which are known to involve the aspects of glucose metabolism, amino acid metabolism, and fatty acid metabolism. Recently, with the increasing interest to understand the metabolic regulation in cancer, the investigation into the metabolism of endothelial cells has made progress. We herein review the role of endothelial cell metabolism in angiogenesis, with a particular focus on the metabolic regulation of endothelial cells in tumor angiogenesis, which hopes to provide insights for the intervention of tumor angiogenesis in cancer therapy.

Psoriasis, bringing great trouble to patients' life, is a common chronic immune skin disease which is relapsed and difficult to cure. Further understanding of the pathogenesis of psoriasis will be benefit for potential drug targets and the development of therapeutic drugs. In recent years, "interleukin-23/T helper17 (IL-23/Th17) cell axis" has attracted more and more attention in the pathogenesis of psoriasis. Some drugs targeting the cell axis have also been successfully listed in the market to improve psoriasis and achieved good results. This review focuses on the "IL-23/Th17 cell axis" system to elaborate the role of a variety of immune cells involved in the pathogenesis of psoriasis, such as dendritic cells, macrophages, neutrophils and T cells, and summarizes multiple therapeutic antibodies targeting this cell axis in the treatment of psoriasis. In addition, this review also summarizes the current small molecule drugs for the treatment of psoriasis.

Autophagy is a widespread and unique degradation process in eukaryotic cells. When cells are under various stress conditions such as nutritional deficiencies, growth factor deficiencies or hypoxia, autophagy will be initiated to maintain the stability of the internal environment and ensure normal proliferation and differentiation. At present, research on autophagy-related targets is mostly focused on tumor cells. In contrast, research on fungal autophagy targets is still limited. Autophagy plays an important role in growth, development and morphological changes of fungal cells, suggesting that research on fungal autophagy as a drug target should be useful. This article reviews the signal regulation and detection strategies for autophagy in fungal cells, and provides a research basis for the screening of antifungal drugs targeting autophagy-related proteins.

Prostate cancer is the most common malignant tumor of male reproductive system, which seriously threatens men's health. It has been shown that the existence of zinc ions can inhibit the growth of prostate cancer cells. In addition, photothermal treatment of cancer is attracting more and more attention due to its high accuracy and efficiency. In this study, zinc ions loaded black phosphorus nanosheets (BP-Zn) were prepared, and the photothermal therapy efficiency of the system on human prostate cancer cells (PC-3) was evaluated. The inhibition effect of zinc ions on PC-3 cells was studied. It was demonstrated that the toxicity of zinc ions on PC-3 cells was concentration- and time-dependent. Moreover, it can be seen from in vitro photothermal therapy that the treatment effect of black phosphorus assisted by zinc ions is superior to that of black phosphorus alone. This study further studied the in vivo therapeutic effect of BP-Zn. The results once again confirmed that the combinational photothermal treatment of zinc ions and BP had excellent anti-tumor effect. The animal procedures were approved by the Animal Ethics Committee of Tsinghua Shenzhen International Graduate School.

The complexity of tumor microenvironment brings both challenges and opportunities for targeted drug delivery. On the one hand, using the special characteristic as stimuli, we can construct a variety of responsive drug delivery systems for tumor targeting. On the other hand, the abnormal vasculature and dense extracellular matrix in solid tumor become formidable barriers to the nanoparticles delivery, which greatly reduces the drug delivery efficiency. Lots of researches focus on regulating the tumor microenvironment to make it more conducive to drug delivery. In this review, we will highlight the recent advances both in tumor microenvironment responsive nano-drug delivery systems design and tumor microenvironment regulation to improve tumor targeted delivery efficiency, and discuss the existing problems and future development.

In this study, the model of Propionibacterium acnes/lipopolysaccharide (P. acnes/LPS)-induced acute liver injury in mice was employed to investigate the protective effects of Fuzheng Yanggan Fomula (FYF) on acute liver injury. The effects of FYF on the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and interleukin-1β (IL-1β) in the serum, and the levels of malondialdehyde (MDA), oxygen radical absorbance capacity (ORAC), and glutathione (GSH) were examined in the livers of mice treated with P. acnes/LPS; The protein expression levels of Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and IL-1β in liver tissues were detected by Western blot; Furthermore, hematoxylinendash-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemical assay were used to observe pathological changes, apoptosis index, and inflammation infiltration of the liver tissue sections. All animal welfare and experimental procedures were followed by the Animal Ethics Committee of Jinan University. We conclude that FYF could alleviate P. acnes/LPS induced pathological damage and inflammatory infiltration in the liver of mice. Meanwhile, FYF decreases the contents of ALT, AST, IL-1β, and MDA, increases the contents of ORAC and GSH, and downregulates the expression of caspase-1 and IL-1β proteins. Collectively, these findings suggested that FYF could alleviate P. acnes/LPS induced acute liver injury in mice by inhibiting the activation of NLRP3 inflammasome, which provides a theoretical basis and a new drug target for the prevention and treatment of liver injury.

To date, CRISPR/Cas systems represent the most widely used tool for genome editing; however, its application scope for gene therapy has been largely limited due to its limited efficiency in activating homologydirected repair for DNA and off-target effect. Base editing is a new CRISPR/Cas-based genome-editing strategy, which allows single nucleotide to be precisely corrected in a narrow window scope on the target DNA or RNA by taking advantage of different nucleobase deaminases. Base editors include cytosine base editors (CBEs) and adenine base editors (ABEs), which can induce the conversions from C·G to T·A and A·T to G·C, respectively. Base editors work independently of double-strand DNA breaks (DSBs) and DNA donor templates, and thus they are extensively adopted for a wide range of therapeutic applications for genetic diseases, largely owing to their high efficiency and great specificity. In this review, we summarize the development of base editors and their potentials as therapeutic drugs for treating genetic diseases, and future outlooks are also discussed.

To target neovasculature and tumor cells, a novel cationic liposome with verteporfin (BPD) active-loaded in lumen (CLL) was designed and its basic in vitro and in vivo behaviors were evaluated in this study. Calcium acetate gradient loading method was applied to encapsulate BPD actively and cationic lipid (2, 3-dioleoy-loxy-propyl)-trimethylammonium (DOTAP) was added by post-insertion for the positive charge of CLL. Results of characterization showed that the diameter and zeta-potential of CLL were around 100 nm and 28 mV, respectively. Compared with passive loading liposomes, CLL significantly enhanced the stability of BPD loading. What's more, the loaded BPD in lumen could switch off the fluorescence and photosensitization during blood circulation by homo-fluorescence resonance energy transfer (homo-FRET) effect, leading to the diminished phototoxicity to normal tissues. In vitro cellular uptake and cytotoxicity assay exhibited that positive charge dramatically enhanced the uptake of CLL both in vascular endothelial cells and tumor cells leading to superior therapeutic efficacy. In vivo study further showed that CLL reduced the clearance rate and increased tumor accumulation compared with passive loading group. Quantitative results of exvivo organ indicated that negligible CLL distributed in normal organs contributing to low phototoxicity. Animal experiments were conducted according to the Guidelines of the Experimental Animal Ethics Committee of Peking University Health Science Center and International Animal Experiments. In conclusion, we successfully designed a novel cationic targeting liposome that overcame the limitations of passive loading and significantly enhanced the efficacy of photodynamic therapy.