Histone deacetylase (HDAC) is usually abnormally overexpressed, which mainly leads to the transcriptional repression of tumor suppressor genes. Histone deacetylase inhibitors (HDIs) exert anti-tumor biological effects by regulating nucleosome structure, inhibiting HDAC activity, and controlling the expression of tumor suppressor genes. There are currently 5 drugs on the market, but only for peripheral T-cell lymphoma and cutaneous T-cell lymphoma. In solid tumors, most of the HDAC inhibitors used have failed to achieve effective therapeutic effects. Phosphoinositide 3-kinase (PI3K) is the starting node of the PI3K-AKT-mTOR signaling pathway, which plays a very important role in the proliferation, migration, invasion, and differentiation of tumor cells. The abnormal activation of PI3K is closely related to the occurrence and development of tumors, and the combined use of HDAC and PI3K inhibitors and HDAC/PI3K dual-target inhibitors show synergistic anticancer activity. This article introduces the anti-tumor clinical and preclinical research progress of representative HDAC inhibitors and PI3K inhibitors, as well as HDAC/PI3K dual-target inhibitors.

In traditional oral practice, the presystemic interactions with gut microbiota is an important mechanism underlying the holistic health benefits of Chinese herbal medicines (CHMs), making the study of CHMs distinct from the research of Western medicines of which the systemic exposure (level in blood) is the starting point and the core. Gut microbial metabolism complements host metabolism in maintaining metabolic homeostasis of many biologically important endogenous molecules and the disposition of numerous exogenous compounds. Among them, the widely distributed gut bacterial β-glucuronidases (BGUSs) coordinate with host UDP-glucuronosyltransferases (UGTs) to play a role in the occurrence and intervention of diseases by affecting the glucuronidation homeostasis and altering the intestinal local and/or systemic exposure of endogenous compounds and xenobiotics. On one hand, many ingredients of CHMs undergo enterohepatic circulation; On the other hand, CHMs can act on BGUSs directly or indirectly change the distribution and function of BGUSs through reprogramming gut microbiome. The multiple interactions between BGUSs and CHMs may play an important role in the overall therapeutic benefits of CHMs. This work firstly summarizes the latest research progress on BGUSs; then the physiological, pathological and pharmacological significance of BGUSs are exemplified with representative endogenous and exogenous compounds from the aspects of nutrient utilization, metabolic homeostasis, and therapeutic response based on the varied substrate spectra of BGUSs; finally, the scattered data in literature were integrated to summarize the multiple interactions between BGUSs and CHMs, highlighting the important role of BGUSs in the holistic actions of CHMs.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. However, due to its complex pathogenesis, there are no officially approved drugs for NAFLD treatment currently. Therefore, it is extremely urgent to find safe and effective anti-NAFLD drugs. Nowadays, lipid-lowering drugs are the main option for NAFLD therapy, but the clinical efficacy of chemical drugs is also very limited, as well as the frequent side effects or adverse reactions. Traditional Chinese medicine (TCM) has attracted more and more attention in the treatment of NAFLD due to its unique advantages through multiple targets and pathways with few side effects. In recent years, numerous studies have demonstrated that the imbalance of gut microbiota plays an important role in the occurrence and development of NAFLD. This review systematically summarizes the experimental and clinical evidences of TCM active compounds and TCM prescription involved in the regulation of intestinal flora in the treatment of NAFLD in recent years, so as to provide a reference for further exploring the pathogenesis of NAFLD and exploring TCM treatment methods.

It was found that intestinal flora could directly regulate mitochondria of intestinal epithelial cells or indirectly through the nucleus. This effect is associated with the flora metabolites such as short-chain fatty acids (SCFAs), hydrogen sulfide (H₂S) and nitric oxide (NO). These metabolites are involved in mitochondria-related energy metabolic processes and the production of mitochondrial reactive oxygen species (mtROS), and even in the immune response of the whole organism. Numerous studies have also shown that intestinal flora metabolites and mitochondria have become a hot spot for research on the mechanism of action of traditional Chinese medicine, but the research on the mechanism of association between them is not yet in-depth. In this review, we summarize the mechanism of mitochondrial regulation of intestinal epithelial cells by intestinal flora metabolites and herbal interventions to provide a theoretical basis for targeting intestinal microbes and mitochondria to regulate body metabolism and health.

Decoction is one of the traditional dosage forms of traditional Chinese medicines (TCMs). In addition to small molecular components, decoction also contains polysaccharides and other macromolecular components. For a long time, ethanol precipitation has been commonly used during TCMs based new drug development to remove "ineffective macromolecular components", and enrich "active small molecules components", so as to improve the subsequent formability of the preparations. With the recognition of the relationships between gut microbiota and host health/disease, and the potential prebiotic effects of natural polysaccharides, the important values of polysaccharides in TCMs decoctions have been gradually emerged. Based on the representative findings of our own research and the literatures, the potential prebiotics function of TCMs polysaccharides were reviewed regarding its related effects on host physiological and pathological processes of metabolic function, bowel function, immunity, inflammation, emotion and tumor, on the metabolism and absorption of coexisting small molecule components, as well as the structure-function features, so that the meanings of polysaccharides in TCMs decoction were discussed and emphasized, and hopefully to provide enlightenment for the premise of attaching importance to the existence of polysaccharide components in the process of innovative drug research and development based on classical and clinical TCMs prescriptions.

Depression is a common emotional mental disorder. Patients not only continuously showed depression, pessimism and apathy in mood, but also have gastrointestinal symptoms such as anorexia and constipation in body. Widely attention has been also received in the potential biological role of gut microbiota in the pathogenesis of depression. It plays an important role in the interaction between the intestine and the brain, not only affecting the intestinal barrier function, but also maintaining the homeostasis of host through the microbiota-gut-brain axis. In recent years, the traditional Chinese medicine (TCM) has the advantages of obvious therapeutic effects and few side effects when treating neuropsychiatric diseases, such as depression. The pharmacological mechanism of TCM exerting antidepressant effects by regulating the structure of gut microbiota, reducing displacement, and maintaining the normal function of gut microbiota has been also widely concerned. By investigating the relevant literature in recent years, this paper summarizes the antidepressant effect of TCM in different directions such as Chinese medicine monomer, single medicine and compound medicine. And this paper reviews the antidepressant effects and mechanisms of TCM at different levels, such as the correction of gut microbiota structure, the regulation of immunity, the transplantation of gut microbiota and the regulation of its metabolites. This paper will provide a basis for further explaining the mechanism of gut microbiota in depression and the mechanism of antidepressant effect of TCM.

The aim of this study was to investigate the efficacy and mechanism of Dengzhan Shengmai (DZSM) against nonalcoholic fatty liver diseases (NAFLD). The animal experiment program was reviewed and approved by the Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences. The NAFLD model of Syrian golden hamsters was established by high fat diets. After 6 weeks of DZSM treatment, the serum lipid, hepatic lipid accumulation, liver function and inflammatory response were determined. The regulations of gut microbiota and short-chain fatty acids were detected by 16S rRNA gene sequencing and gas chromatography-mass spectrometry method, respectively. The gut barrier function was evaluated by enzyme linked immunosorbent assay (ELISA), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot and histopathological methods and further verified in HepG2 cells. The results showed that the efficacy of DZSM against NAFLD was remarkably reduced after removal of the gut microbiota. The study of mechanism showed that DZSM significantly regulated the composition of gut microbiota, promoted the production and absorption of intestinal short-chain fatty acids, then leading to the reduction of hepatic lipid accumulation. Moreover, after DZSM treatment, the decreased lipopolysaccharide (LPS) level by improving the intestinal barrier function significantly inhibited the hepatic inflammation through down-regulating Toll like receptor 4 (TLR4)-nuclear factor kappa B (NFKB) signaling pathway. These results indicate that DZSM inhibits NAFLD via regulating intestinal microenvironment.

The biological behavior of carbon dots, especially the mechanism of cellular uptake and intracellular distribution, is the basis of its biomedical applications. In this paper, blue fluorescent carbon quantum dots were synthesized by hydrothermal method with Poria cocos polysaccharide as raw material, and the specific biological behavior of carbon dots entering cells was explored to evaluate its biological activity. It was characterized by transmission electron microscopy, UV-vis absorption spectroscopy, fluorescence spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Two different cell lines, immunocytes-RAW264.7 cells (mouse mononuclear macrophages cells) and cancer cells-4T₁ cells (mouse breast cancer cells), were used as the research objects to study the uptake kinetics, uptake pathway, distribution and efflux of polysaccharide carbon dots in cells. The results showed that the carbon dots have a size distribution of 2 to 10 nm, and the average size was 6.85 nm. The carbon dots were mainly composed of C, O and N elements, with abundant surface functional groups such as -OH, C=O, C-N and C=C, and the fluorescence quantum yield was 4.72%. Carbon dots enter cells in a certain concentration and time dependence. Different cell lines have different uptake pathways. RAW264.7 cells enter the cells mainly by macrophage-specific phagocytosis, and a small part of the endocytosis is mediated by caveolin, while 4T₁ cells are mainly mediated by grid protein endocytosis and giant cell drinking process. In summary, the synthesized carbon dots have good fluorescence properties, low cytotoxicity and excellent biocompatibility, which can be used for cell imaging applications.

An analytical method was developed for determination of 7 aminoglycosides antibiotics in bear bile powder by hydrophilic interaction liquid chromatography tandem mass spectrometry. The samples were purified by mix-mode weak cation exchange and reversed-phase SPE. Waters ACQUITY UPLC BEH Amide column (100 mm × 3.0 mm, 1.7 μm) was used with 0.2% formic acid aqueous solution-0.2% formic acid acetonitrile solution as mobile phases by gradient elution. The aminoglycosides were detected by electrospray ionization mass spectrometry in positive mode with multiple reaction monitoring (MRM) mode. Spectinomycin, streptomycin, amikacin, kanamycin, tobramycin, apramycin and neomycin possessed good linear correlation in the respective concentration ranges, with the correlation coefficients more than 0.99. The mean recoveries at 3 spiked levels were in the range of 61.3%~127.3%, and the RSDs were 0.1%~1.9%. The limits of quantification were 0.2~1.0 mg·kg^-1. The method had been applied to the analysis of actual samples.

This study investigated the protective effect and related mechanisms of Xinhui citrus fermentation liquor on mice with ulcerative colitis. Animal experiments follow the rules of Animal Ethics Committee of Southern Medical University. C57BL/6 mice were given 3% dextran sodium sulfate (DSS) for 6 days to induce acute ulcerative colitis. During this period, Xinhui citrus fermentation liquor, decoction of Citrus reticulata blanco (both orally administrated with 300 mg·kg^-1·d^-1 crude polysaccharide) or positive drug 5-aminosalicylic acid (100 mg·kg^-1·d^-1) were gavaged continuously for 9 days. Cecal contents were collected for 16S rRNA sequencing analysis. The levels of inflammatory factors, tight junction proteins and nuclear factor erythroid 2 related factor 2 / Nod-like receptor protein 3 (Nrf2/NLRP3) pathway related proteins in the colon were detected by real-time PCR (RT-PCR), immunofluorescence and Western blot. Our results showed that Xinhui citrus fermentation liquor and Citrus reticulata blanco protected against UC-induced weight loss, diarrhea, bloody stool, and colon shortening. The mRNA and protein levels of pro-inflammatory factors, such as interleukin 6 (Il-6) and CXC chemokine ligand 10 (Cxcl10) and NLRP3 inflammasome were significantly decreased; the mRNA levels of colon anti-inflammatory factor (Il-10), tight junction protein [zonula occludens-1 (Zo-1), occludin, claudin-1], mucin 2 (Muc2), Nrf2, as well as the mRNA and protein levels of NAD(P)H quinine oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) were significantly increased. In addition, Xinhui citrus fermentation liquor increased the abundance of Akkermansia and reduced the abundance of harmful bacteria Enterococcus and Streptococcus. The correlation analysis showed that the abundance of Akkermansia was positively correlated with anti-inflammatory factors, tight junction protein and the related genes levels of Nrf2 signaling pathway. In summary, Xinhui citrus fermentation liquor ameliorates acute ulcerative colitis in mice via regulating intestinal bacteria homeostasis and Nrf2/NLRP3 pathway to repair intestinal mucosa.