In response to a wide range of stimulations, host cells activate pyroptosis, a kind of inflammatory cell death which is provoked by the cytosolic sensing of danger signals and pathogen infection. In manipulating the cleavage of gasdermins (GSDMs), researchers have found that GSDM proteins serve as the real executors and the deterministic players in fate decisions of pyroptotic cells. Whether inflammatory characteristics induced by pyroptosis could cause damage the host or improve immune activity is largely dependent on the context, timing, and response degree. Here, we systematically review current points involved in regulatory mechanisms and the multidimensional roles of pyroptosis in several metabolic diseases and the tumor microenvironment. Targeting pyroptosis may reveal potential therapeutic avenues.

Gastrointestinal cancer is currently one of the main causes of cancer death, with a large number of cases and a wide range of lesioned sites. A high fat diet, as a public health problem, has been shown to be correlated with various digestive system diseases and tumors, and can accelerate the occurrence of cancer due to inflammation and altered metabolism. The gut microbiome has been the focus of research in recent years, and associated with cell damage or tumor immune microenvironment changes via direct or extra-intestinal effects; this may facilitate the occurrence and development of gastrointestinal tumors. Based on research showing that both a high fat diet and gut microbes can promote the occurrence of gastrointestinal tumors, and that a high fat diet imbalances intestinal microbes, we propose that a high fat diet drives gastrointestinal tumors by changing the composition of intestinal microbes.

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In this study, the aim was to investigate the effect of bergenin on immune function and antioxidation in cyclophosphamide (Cy)-induced immunosuppressed mice. Firstly, we estimated its effect on immune organs. Histological analysis and indexes of immune organs showed that cyclophosphamide exhibited spleen and thymus injury compared with the normal control, which was alleviated by bergenin. Secondly, bergenin also enhanced the humoral immune function through increasing the level of IgM and IgG in serum. Thirdly, bergenin also enhanced the cellular immune function. The results indicate that bergenin increased peritoneal macrophage functions, the proliferation of T and B lymphocytes, NK and CTL cell activities, and T (CD4+ and CD8+) lymphocyte subsets. Besides, bergenin also had the ability to modulate the Th1/Th2 balance. Moreover, bergenin prevented the Cy-induced decrease in numbers of peripheral RBC, WBC and platelets, providing supportive evidence for their anti-leukopenia activities. Finally, bergenin also reversed the Cy-induced decrease in the total antioxidant capacity including activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). In conclusion, bergenin protected against Cy-induced adverse reactions by enhancing humoral and cellular immune functions and augmenting antioxidative activity and could be considered as a potential immunomodulatory agent.

Cancer-cell-released exosomal microRNAs (miRNAs) are important mediators of cell-cell communication in the tumor microenvironment. In this study, we sequenced serum exosome miRNAs from esophageal squamous cell carcinoma (ESCC) patients and identified high expression of miR-320b to be closely associated with peritumoral lymphangiogenesis and lymph node (LN) metastasis. Functionally, miR-320b could be enriched and transferred by ESCC-released exosomes directly to human lymphatic endothelial cells (HLECs), promoting tube formation and migration in vitro and facilitating lymphangiogenesis and LN metastasis in vivo as assessed by gain- and loss-of-function experiments. Furthermore, we found programmed cell death 4 (PDCD4) as a direct target of miR-320b through bioinformatic prediction and luciferase reporter assay. Re-expression of PDCD4 could rescue the effects induced by exosomal miR-320b. Notably, the miR-320b-PDCD4 axis activates the AKT pathway in HLECs independent of vascular endothelial growth factor-C (VEGF-C). Moreover, overexpression of miR-320b promotes the proliferation, migration, invasion, and epithelial-mesenchymal transition progression of ESCC cells. Finally, we demonstrate that METTL3 could interact with DGCR8 protein and positively modulate pri-miR-320b maturation process in an N6-methyladenosine (m6A)-dependent manner. Therefore, our findings uncover a VEGF-C-independent mechanism of exosomal and intracellular miR-320b-mediated LN metastasis and identify miR-320b as a novel predictive marker and therapeutic target for LN metastasis in ESCC.

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Breast cancer is the major cause of cancer death worldwide in women. Patients with metastasis have poor prognosis and the mechanisms of breast cancer metastasis are not completely understood. Long non-coding RNAs (lncRNAs) have been shown to have crucial roles in breast cancer development and progression. However, the underlying mechanisms by which lncRNA-driven breast cancer metastasis are unknown. The main objective of this paper is to explore a functional lncRNA and its mechanisms in breast cancer. Here we identified a novel lncRNA AC073352.1 that was significantly upregulated in breast cancer tissues and was associated with advanced TNM stages and poor prognosis in breast cancer patients. In addition, AC073352.1 was found to promote the migration and invasion of breast cancer cells in vitro and enhance breast cancer metastasis in vivo. Mechanistically, we elucidated that AC073352.1 interacted with YBX1 and stabilized its protein expression. Knock down of YBX1 reduced breast cancer cell migration and invasion and could partially reverse the stimulative effects of AC073352.1 overexpressed on breast cancer metastasis. Moreover, AC073352.1 might be packaged into exosomes by binding to YBX1 in breast cancer cells resulting in angiogenesis. Collectively, our results demonstrated that AC073352.1 promoted breast cancer metastasis and angiogenesis via binding YBX1, and it could serve as a promising, novel biomarker for prognosis and a therapeutic target in breast cancer.

Identification of active ingredients, and their structures, from Bletilla striata and investigation of the antioxidative and anti-inflammatory responses in vitro and in vivo.