Cancer stem cells (CSCs) are crucial components of the tumor microenvironment that take part in tumor initiation, progression, recurrence, metastasis, and resistance to chemotherapy. This study explores the mechanisms through which CSCs maintain their stemness, especially in tumors of colorectal cancer (CRC), which thus far remain uncertain. Our findings indicated that the expression of miR-20b-5p is negatively correlated with that of metastasis-associated lung adenocarcinoma transcript-1 (MALAT1, r = −0.928, p = 0.023) and Oct4 (r = −0.894, p = 0.041) in CRC cells. We hypothesized that there may be some targeted regulatory relationships among MALAT1, miR-20b-5p, and Oct4. We proceeded to show that both si-MALAT1 and miR-20b-5p-mimic attenuated microsphere formation and self-renewal capacity, decreased the proportion of CSCs, and downregulated the expression of proteins associated with tumor cell stemness maintenance (Oct4, Nanog, sex-determining region Y-box 2, and Notch1) and cellular metabolism (glucose transporter 1, lactate dehydrogenase B, hexokinase 2, and pyruvate kinase isozyme M2) in HCT-116 cells in vitro. In addition, a xenograft model based on Balb/c mice demonstrated that the administration of either si-MALAT1 or miR-20b-5p-mimic suppressed the tumorigenicity of HCT-116 cells in vivo. The underlying mechanisms may involve the targeting of the tumor cell stemness maintenance-related factor Oct4 by miR-20b-5p. For the first time, we present the possible underlying effects of MALAT1 in influencing the stem cell-like properties of CRC cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated. K E Y W O R D S cancer stem cells, colorectal cancer, MALAT1, miR-20b-5p/Oct4 axis, stemness

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Herbal medicine is a major part of traditional Chinese medicine (TCM), which is evolved as a system of medical practice from ancient China. The use of herbal medicine is mainly based on practice and theories and concepts rooted in ancient philosophy. In the era of evidence-based medicine, it is essential to accurately evaluate herbal remedy with standard/modern medical practice approaches. Tetradium ruticarpum (A. Juss.) Hartley (TR), a medicinal plant with diversify bioactive components, has been broadly used to treat pain and gastrointestinal disorders in TCM. However, TR has also been reported to have potential toxicity by long-term use or excessive doses, though the associated compounds are yet to be identified. TR is usually processed, and/or combined with other herbs in TCM formulas in order to achieve a synergistic effect or reduce its toxicity. Since processing or polyherbal formulation of TR may lead to changes in its chemical composition and contents, quality, efficacy and toxicity, comparison of TR samples before and after processing, as well as its combination with other medicines, would provide useful knowledge of bioactive compounds, efficacy and toxicity of this valuable medicinal plant. Here we reviewed the recent studies about the phytochemistry, pharmacokinetic behaviors and toxicity of TR under various processing or polyherbal formulation conditions, which would expand our understanding of mechanisms of TR's efficacy and toxicity and be valuable for quality control in industrial manufacturing, future medicinal research, and safety and rational use of TR in TCM.

Inflammatory bowel disease (IBD) is a group of autoimmune diseases, including ulcerative colitis and Crohn’s disease, characterized by nonspecific inflammation in the gut. Total glycoside of peony (TGP) has been widely used for treatment of autoimmune diseases because of its pharmacological effects. However, it is lack of depth in whether TGP regulate T helper 17 cell (Th17) / T regulatory cell (Treg) immune balance or interleukin 23 (IL-23) / IL-17 axis to achieve the goal of treating IBD. Hence, the aim of this study was to investigate the effects of TGP on experimental colitis mice and the related mechanisms. In the present study, we demonstrated that administration of TGP effectively attenuates colonic inflammation of TNBS-induced colitis mice, mainly reflected in significantly improved clinical parameters, reduced inflammatory response and myeloperoxidase (MPO) activity, even stronger systemic immune ability and effective improvement of Th17/Treg immune disorders. In addition, there was a stronger immunosuppressive ability in a positive cluster of differentiation 4 (CD4[Formula: see text]) T-lymphocytes from the TGP treated mouse colon, characterized by the inhibition of high levels of inflammatory factors and increased regulatory T cells. Importantly, high-dose TGP has similar therapeutic effects as salicylazosulfapyridine (SASP) on IBD treatment. The potential mechanisms might be, at least in part, related to the adjustment of imbalance of Th17/Treg cells and the inhibition of IL-23/IL17 inflammatory signal axis.

Fibrosis is a common process of tissue repair response to multiple injuries in all chronic progressive diseases, which features with excessive deposition of extracellular matrix. Fibrosis can occur in all organs and tends to be nonreversible with the progress of the disease. Different cells types in different organs are involved in the occurrence and development of fibrosis, that is, hepatic stellate cells, pancreatic stellate cells, fibroblasts and myofibroblasts. Various types of programmed cell death, including apoptosis, autophagy, ferroptosis and necroptosis, are closely related to organ fibrosis. Among these programmed cell death types, necroptosis, an emerging regulated cell death type, is regarded as a huge potential target to ameliorate organ fibrosis. In this review, we summarize the role of necroptosis signalling in organ fibrosis and collate the small molecule compounds targeting necroptosis. In addition, we discuss the potential challenges, opportunities and open questions in using necroptosis signalling as a potential target for antifibrotic therapies.

Curcumin, a well-known hydrophobic polyphenol extracted from the rhizomes of turmeric (Curcuma longa L.), has attracted great interest in the last ten years due to its multiple pharmacological activities. A growing body of evidence has manifested that curcumin has extensive pharmacological activities including anti-inflammatory, anti-oxygenation, lipid regulation, antiviral, and anticancer with hypotoxicity and minor adverse reactions. However, the disadvantages of low bioavailability, short half-life in plasma, low drug concentration in blood, and poor oral absorption severely limited the clinical application of curcumin. Pharmaceutical researchers have carried out plenty of dosage form transformations to improve the druggability of curcumin and have achieved remarkable results. Therefore, the objective of this review summarizes the pharmacological research progress, problems in clinical application and the improvement methods of curcumin’s druggability. By reviewing the latest research progress of curcumin, we believe that curcumin has a broad clinical application prospect for its wide range of pharmacological activities with few side effects. The deficiencies of lower bioavailability of curcumin could be improved by dosage form transformation. However, curcumin in the clinical application still requires further study regarding the underlying mechanism and clinical trial verification.