[Decursin affects proliferation, apoptosis, and migration of colorectal cancer cells through PI3K/Akt signaling pathway].

We investigated the effects of decursin on the proliferation, apoptosis, and migration of colorectal cancer HT29 and HCT116 cells through the phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway. Decursin(10, 30, 60, and 90 µmol·L~(-1)) was used to treat HT29 and HCT116 cells. The survival, colony formation ability, proliferation, apoptosis, wound hea-ling area, and migration of the HT29 and HCT116 cells exposed to decursin were examined by cell counting kit-8(CCK8), cloning formation experiments, Ki67 immunofluorescence staining, flow cytometry, wound healing assay, and Transwell assay, respectively. Western blot was employed to determine the expression levels of epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, B-cell lymphoma/leukemia-2(Bcl-2), Bcl-2-associated X protein(Bax), tumor suppressor protein p53, PI3K, and Akt. Compared with the control group, decursin significantly inhibited the proliferation and colony number and promoted the apoptosis of HT29 and HCT116 cells, and it significantly down-regulated the expression of Bcl-2 and up-regulated the expression of Bax. Decursin inhibited the wound healing and migration of the cells, significantly down-regulated the expression of N-cadherin and vimentin, and up-regulated the expression of E-cadherin. In addition, it significantly down-regulated the expression of PI3K and Akt and up-regulated that of p53. In summary, decursin may regulate epithelial-mesenchymal transition(EMT) via the PI3K/Akt signaling pathway, thereby affecting the proliferation, apoptosis, and migration of colorectal cancer cells.

How autophagy, a potential therapeutic target, regulates intestinal inflammation.

Inflammatory bowel disease (IBD) is a group of disorders that cause chronic inflammation in the intestines, with the primary types including ulcerative colitis and Crohn's disease. The link between autophagy, a catabolic mechanism in which cells clear protein aggregates and damaged organelles, and intestinal health has been widely studied. Experimental animal studies and human clinical studies have revealed that autophagy is pivotal for intestinal homeostasis maintenance, gut ecology regulation and other aspects. However, few articles have summarized and discussed the pathways by which autophagy improves or exacerbates IBD. Here, we review how autophagy alleviates IBD through the specific genes (e.g., ATG16L1, IRGM, NOD2 and LRRK2), crosstalk of multiple phenotypes with autophagy (e.g., Interaction of autophagy with endoplasmic reticulum stress, intestinal antimicrobial defense and apoptosis) and autophagy-associated signaling pathways. Moreover, we briefly discuss the role of autophagy in colorectal cancer and current status of autophagy-based drug research for IBD. It should be emphasized that autophagy has cell-specific and environment-specific effects on the gut. One of the problems of IBD research is to understand how autophagy plays a role in intestinal tract under specific environmental factors. A better understanding of the mechanism of autophagy in the occurrence and progression of IBD will provide references for the development of therapeutic drugs and disease management for IBD in the future.

[Thoughts of treatment of tumor diseases based on toxic pathogen theory].

The toxic pathogen theory, an important part of the theories of traditional Chinese medicine(TCM), began in the Qin and Han dynasties, formed in the Jin, Sui, Tang, and Song dynasties, developed rapidly in the Ming and Qing dynasties, and conti-nued to develop in contemporary times based on the achievements of its predecessors. The continuous exploration, practice, and inheri-tance of many medical practitioners over the generations have facilitated the enrichment of its connotation. The toxic pathogen is violent, fierce, dangerous, prolonged, rapid in transmission, easy to hurt the internal organs, hidden, and latent, with many changes, and it is closely related to the development of tumor diseases. TCM has a history of thousands of years in the prevention and treatment of tumor diseases. It is gradually realized that the etiology of tumor is mainly attributed to the deficiency of healthy Qi and excess of to-xic pathogen, and the struggle between healthy Qi and toxic pathogen runs through the whole course of tumor, with the deficiency of healthy Qi as the prerequisite and the invasion of toxic pathogen as the root of the occurrence. The toxic pathogen has a strong carcinogenic effect and is involved in the whole process of tumor development, which is closely related to the malignant behaviors of tumors, including proliferation, invasion, and metastasis. This study discussed the historical origin and modern interpretation of the toxic pathogen theory in the prevention and treatment of tumors, with aims of sorting out the theoretical system based on the toxic pathogen theory in the treatment of tumor diseases, and illustrating the importance of the toxic pathogen theory in the treatment of tumors in the context of modern research on pharmacological mechanisms and the development and marketing of relevant anti-tumor Chinese medicinal preparations.

Parallel faction analysis combined with two-dimensional correlation spectroscopy reveal the characteristics of mercury-composting-derived dissolved organic matter interactions.

Dissolved organic matter (DOM) is regarded as the environmentally friendly substance. Strong complexes could be formed between DOM and heavy metals. Thus, the distribution, bioavailability, toxicity, and fate of heavy metals could be controlled in the environment. The widely spread method for characterizing metal-organic interactions is restricted to combine parallel faction analysis (PARAFAC) with the complexation model. However, a DOM PARAFAC component always contains two or more peaks. Therefore, the traditional method cannot reveal the inner changes of PARAFAC components or whether all the DOM peaks in one PARAFAC component are bound with metal during the metal-organic binding process. In this work, two-dimensional correlation spectroscopy (2DCOS) combined with PARAFAC and the complexation model were employed to reveal the binding speed and ability of different fluorescent peaks from DOM PARAFAC components during the binding process of mercury (Hg2+) to DOM. The results in this study showed that during the Hg2+-DOM binding process, fluorescent peaks in tryptophan-like component all presented Hg2+-binding ability. However, only humic-like component ligands showed Hg2+-binding ability. With these promising results, the true Hg2+ binding rate and ability of different DOM ligands can be revealed, which is helpful for addressing environmental pollution.

[Bone Morphogenetic Proteins from CT26 Regulate the Expression of PD-L1 in Murine Dendritic Cells and Macrophages].

OBJECTIVES: To analyze the influence of bone morphogenetic proteins (BMPs) from CT26 on PD-L1 of dendritic cells and macrophages. METHODS: In vivo, we respectively inoculated CT26 colon cancer cells subcutaneously and intraperitoneally to BALB/c mice.The mice were randomly assigned to three groups and treated with normal saline; BMPs inhibitor LDN193189; BMPs inhibitor LDN193189 combined with paclitaxel, respectively. The treatments started on the eighth day after inoculating, when the tumor volume reached 150 mm3 or the abdominal circumference was greater than 6 cm. After 2 weeks of treatments, the mice were sacrificed.The counts of dendritic cells and macrophages and the expression of PD-L1 in tumors or ascites were detected by flow cytometry (FCM).In vivo, the dendritic cells and macrophages from normal BALB/c mice bone marrow were exposed to: no treatment; CT26 supernatant; CT26; CT26 supernatant and LDN193189; CT26 and LDN193189; CT26 supernatant, LDN193189 and paclitaxel; CT26, LDN193189 and paclitaxel. BMPs from CT26 was detected by ELISA.The counts of dendritic cells and macrophages and their PD-L1 expressions were detected by FCM. IRF-1 expression was detected by real-time (RT)-PCR and Western blot. RESULTS: In vivo, LDN193189 treated mice had the greatest tumor size or abdominal circumference, with least dendritic cells andCM(155.3mm]macrophages and expressions of PD-L1.In vivo, ELISA test results showed that the concentration of BMPs in CT26 supernatant was (0.59±0.09) ng/mL. FCM, RT-PCR and Western blot showed that dendritic cells and macrophages exposed to CT26 supernatant and LDN193189 or CT26 and LDN193189 expressed the least PD-L1 and IRF-1, which was close to those without treatment. While added the PTX to the above treatment, the expressions of PD-L1 and IRF-1 increased in the test results. CONCLUSIONS: BMPs from CT26 up-regulate the expression of PD-L1 in murine dendritic cells and macrophages.