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With the development of precision medicine, visual and traceable treatments are highly desirable for cancer therapy. However, researchers and clinicians remain confused regarding where the drug distributes and location of the tumor, when the drug is released and when to irradiate the tumor, and how the drug presents antitumor activity, all of which hinders assessment of the cancer patient's condition and formulation of a follow-up treatment scheme for clinicians. Here, a supramolecular self-assembly theranostic nanosystem (MWNs) was designed for enhanced reactive oxygen species (ROS)-mediated cell apoptosis guided by dual-modality tumor imaging. Specifically, merocyanine was introduced in cyanine dye to extend its conjugated π-scaffolds, which could preferentially self-assemble into nanovesicles owing to its amphipathy. Furthermore, withaferin A (WA), used as a chemotherapeutic drug, was loaded to construct MWNs. The assembled or disassembled MWNs behaved differently in photoacoustic (PA) intensity and fluorescence signal intensity. The MWNs exhibited stronger PA signals and quenched fluorescence, which monitors their distribution and images the tumor location in vivo , while the disassembled MWNs showed weak PA signals and recovered fluorescence, indicating the release of drug and instructing the appropriate time to irradiate for photodynamic therapy (PDT). Thus, ROS generation introduced by PDT and released WA led to cell apoptosis. This intelligent nanosystem for precise cancer therapy that reveals where the tumor is, when to irradiate the tumor, and how the tumor is cured might establish the basis for biomedical applications of finely controlled platform. [Display omitted] • Precision medicine is highly desirable for cancer treatment. • We developed a theranostic nanosystem for enhanced ROS-mediated cells apoptosis. • Supramolecular self-assembly nanovesicles with dual-modality tumor imaging. • Monitoring of where drug distribute, when drug release and when to laser for PDT. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract As an important component of complementary and alternative medicines, traditional Chinese medicines (TCM) are gaining more and more attentions around the world because of the powerful therapeutic effects and less side effects. However, there are still some doubts about TCM because of the questionable TCM theories and unclear biological active compounds. In recent years, gut microbiota has emerged as an important frontier to understand the development and progress of diseases. Together with this trend, an increasing number of studies have indicated that drug molecules can interact with gut microbiota after oral administration. In this context, more and more studies pertaining to TCM have paid attention to gut microbiota and have yield rich information for understanding TCM. After oral administration, TCM can interact with gut microbiota: (1) TCM can modulate the composition of gut microbiota; (2) TCM can modulate the metabolism of gut microbiota; (3) gut microbiota can transform TCM compounds. During the interactions, two types of metabolites can be produced: gut microbiota metabolites (of food and host origin) and gut microbiota transformed TCM compounds. In this review, we summarized the interactions between TCM and gut microbiota, and the pharmacological effects and features of metabolites produced during interactions between TCM and gut microbiota. Then, focusing on gut microbiota and metabolites, we summarized the aspects in which gut microbiota has facilitated our understanding of TCM. At the end of this review, the outlooks for further research of TCM and gut microbiota were also discussed. [ABSTRACT FROM AUTHOR]

Given the high and increasing prevalence of obesity, the safe and effective treatment of obesity would be beneficial. Here, we examined whether oral hydroxysafflor yellow A (HSYA), an active compound from the dried florets of Carthamus tinctorius L., can reduce high-fat (HF) diet-induced obesity in C57BL/6 J mice. Our results showed that the average body weight of HF group treated by HSYA was significantly lower than that of the HF group (P < 0.01). HSYA also reduced fat accumulation, ameliorated insulin resistance, restored glucose homeostasis, reduced inflammation, enhanced intestinal integrity, and increased short-chain fatty acids (SCFAs) production in HF diet-fed mice. Sequencing of 16S rRNA genes in fecal samples demonstrated that HSYA reversed HF diet induced gut microbiota dysbiosis. Particularly, HSYA increased the relative abundances of genera Akkermansia and Romboutsia, as well as SCFAs-producing bacteria, including genera Butyricimonas and Alloprevotella, whereas it decreased the phyla Firmicutes/Bacteroidetes ratio of HF diet-fed mice. Additionally, serum metabolomics analysis revealed that HSYA increased lysophosphatidylcholines (lysoPCs), L-carnitine and sphingomyelin, and decreased phosphatidylcholines in mice fed a HF diet, as compared to HF group. These changed metabolites were mainly linked with the pathways of glycerophospholipid metabolism and sphingolipid metabolism. Spearman’s correlation analysis further revealed that Firmicutes was positively while Bacteroidetes and Akkermansia were negatively correlated with body weight, fasting serum glucose and insulin. Moreover, Akkermansia and Butyricimonas had positive correlations with lysoPCs, suggestive of the role of gut microbiota in serum metabolites. Our findings suggest HSYA may be a potential therapeutic drug for obesity and the gut microbiota may be potential territory for targeting of HSYA. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 (GLP-1) analogues have been commonly used as add-on medications for patients with Type 2 diabetes mellitus (T2DM). Currently, the development of long-acting GLP-1 analogues which allow the freedom and flexibility of once-weekly injections while maintaining their potency for a relatively long period has become the mainstream. Here, we successfully developed a long-acting human GLP-1(7–37) analogue (BPI-3016) with significantly extended half-life and increased resistance to dipeptidyl peptidase IV (DPP-IV) cleavage by structural modifications of human GLP-1. In vitro activity of BPI-3016 including GLP-1 receptor affinity and stimulation of cyclic adenosine monophosphate (cAMP) production was measured. In vivo activity of BPI-3016 such as its effects on glycemic control, β-cell mass and body weight was evaluated in ob/ob mice, db/db mice, and spontaneous diabetic cynomolgus monkeys. The results indicated that BPI-3016 preserved receptor affinity to GLP receptors, and was capable of stimulating cAMP production. In in vivo pharmacokinetic study, the half-life of BPI-3016 was more than 95 h after single dosing in diabetic cynomolgus monkeys. Also, BPI-3016 reduced fasting and post-prandial plasma glucose levels for up to a week after a single dose; It reduced body mass index (BMI), body fat, improved glucose tolerance and showed insulinotropic effects after once-weekly injection for 7 weeks. In conclusion, BPI-3016 retains the effects of GLP-1 with significantly prolonged half-life, making it a promising therapy for type 2 diabetes with once-weekly treatment in the clinic. [ABSTRACT FROM AUTHOR]

With the development of system biology, traditional Chinese medicine (TCM) is drawing more and more attention nowadays. However, there are still many enigmas behind this ancient medical system because of the arcane theory and complex mechanism of actions. In recent decades, advancements in genome sequencing technologies, bioinformatics and culturomics have led to the groundbreaking characterization of the gut microbiota, a 'forgotten organ', and its role in host health and disease. Notably, gut microbiota has been emerging as a new avenue to understanding TCM. In this review, we will focus on the structure, composition, functionality and metabolites of gut microbiota affected by TCM so as to conversely understand its theory and mechanisms. We will also discuss the potential areas of gut microbiota for exploring Chinese material medica waste, Chinese marine material medica, add-on therapy and personalized precise medication of TCM. The review will conclude with future perspectives and challenges of gut microbiota in TCM intervention. [ABSTRACT FROM AUTHOR]