Background: Cancer associated fibroblasts (CAFs) can remodel tumor microenvironment by secreting exosomes. This study aimed to investigate the role of exosomes derived from cancer-associated fibroblasts in colorectal cancer (CRC) progression. Methods: Circular RNA (circRNA) array was used to identify differentially expressed circRNAs in exosomes from normal fibroblasts (NFs) and CAFs, and confirmed one differentially expressed circRNA circ_0067557 by real-time PCR. The effect of circ_0067557 on proliferation, metastasis, chemoresistance and apoptosis was verified by wound heal, tranwell, CCK8, sphere-forming and flow cytometry assay. Results: Circ_0067557 expression in exosomes from CAFs was higher than those from NFs. CAF-derived exosomes promoted the proliferation, migration, invasion and chemoresistance of CRC cells while suppressed apoptosis. Silencing of circ_0067557 inhibited malignant phenotypes of CRC cells by targeting Lin28A and Lin28B. Moreover, CAF-derived exosomes enhanced the growth of CRC xenograft tumors. Conclusion: Circ_0067557/Lin28A and Lin28B signal axis may be a potential therapy target for CRC.
8 November 2023 in Journal of Translational Medicine
The occurrence and progression of tumors can be established through a complex interplay among tumor cells undergoing epithelial-mesenchymal transition (EMT), invasive factors and immune cells. In this study, we employed single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (ST) to evaluate the pseudotime trajectory and spatial interactive relationship between EMT-invasive malignant tumors and immune cells in primary colorectal cancer (CRC) tissues at different stages (stage I/II and stage III with tumor deposit). Our research characterized the spatiotemporal relationship among different invasive tumor programs by constructing pseudotime endpoint-EMT-invasion tumor programs (EMTPs) located at the edge of ST, utilizing evolution trajectory analysis integrated with EMT-invasion genes. Strikingly, the invasive and expansive process of tumors undergoes remarkable spatial reprogramming of regulatory and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), regulatory T cells (Treg), and exhausted T cells (Tex). These EMTP-adjacent cell are linked to EMT-related invasion genes, especially the C-X-C motif ligand 1 (CXCL1) and CXCL8 genes that are important for CRC prognosis. Interestingly, the EMTPs in stage I mainly produce an inflammatory margin invasive niche, while the EMTPs in stage III tissues likely produce a hypoxic pre-invasive niche. Our data demonstrate the crucial role of regulatory and immunosuppressive cells in tumor formation and progression of CRC. This study provides a framework to delineate the spatiotemporal invasive niche in CRC samples. Graphical Abstract
1 October 2021 in Annals of Translational Medicine
Background: Exploring the relationship between adult iodine intake level and thyroid disease in Shaanxi area is of great significance for adult scientific iodine supplement and individual iodine supplement strategy. At present, the relationship between iodine and incidence of thyroid disease has not been determined. Methods: This study was based on the clinical data of 1,159 patients from the Shaanxi Province aged over 18 years and diagnosed with thyroid-related diseases who were admitted to the Xijing Hospital from 2016 to 2020, and 182 provincial healthy volunteers aged over 18 years who agreed and signed informed consent for physical examination in 2020. The chi-square test and nonparametric test were used to investigate the relationship between iodine intake level and thyroid disease. Results: (I) A total of 1,341 patients were enrolled and observed in this study. The median urinary iodine (MUI) was 233.20 μg/L. Compared with the control, group participants the urine iodine (UI) of those with hyperthyroidism, Hashimoto’s thyroiditis (HT), papillary thyroid cancer (PTC), and benign nodules was significantly different (P<0.05). (II) The incidence of PTC was higher in women with excessive iodine intake and people aged ≥45 years (P0.05). Conclusions: The iodine intake level of adults in Shaanxi is high, which is related to hyperthyroidism, HT, benign nodules, thyroid cancer, and other diseases. There were 3 factors, including excessive iodine intake, age ≥45 years, and female gender, found to be associated with the development of PTC.
Introduction: Gastric cancer (GC) is the fifth most prevalent cancer globally, with the third highest case fatality rate. Neutrophil extracellular traps (NETs) are a reticulated structure of DNA, histones, and antimicrobial peptides produced by active neutrophils that trap pathogens. Even though NETs are associated with poorer recurrence-free survival (RFS) and overall survival (OS), the specifics of this interaction between NETs and cancer cells are yet unknown.Methods: The keywords “neutrophil extracellular traps and gastric cancer” were used in the GEO database for retrieval, and the GSE188741 dataset was selected to obtain the NETs-related gene. 27 NETs-related genes were screened by univariate Cox regression analysis (p < 0.05). 27 NETs-related genes were employed to identify and categorize NETs-subgroups of GC patients under the Consensus clustering analysis. 808 GC patients in TCGA-STAD combined with GES84437 were randomly divided into a training group (n = 403) and a test group (n = 403) at a ratio of 1:1 to validate the NETs-related signature.Results: Based on Multivariate Cox regression and LASSO regression analysis to develop a NETs-related prognosis model. We developed a very specific nomogram to improve the NETs-clinical score’s usefulness. Similarly, we also performed a great result in pan-cancer study with NETs-score. Low NETs scores were linked to higher MSI-H (microsatellite instability-high), mutation load, and immune activity. The cancer stem cell (CSC) index and chemotherapeutic treatment sensitivity were also connected to the NET score. Our comprehensive analysis of NETs in GC suggests that NETs have a role in the tumor microenvironment, clinicopathological features, and prognosis.Discussion: The NETs-score risk model provides a basis for better prognosis and therapy outcomes in GC patients.
The frequency of extreme drought events is increasing, significantly impacting ecosystems worldwide. In China, the grasslands of dryland Inner Mongolia provide a vital ecological resource, highlight the urgent need to understand their response to drought in these arid regions. We investigate vegetation dynamics and soil moisture fluctuations across three grassland types—meadows, typical grasslands, and desert grasslands—utilizing solar-induced fluorescence (SIF), normalized difference vegetation index (NDVI), and soil moisture data from 2001 to 2020. By employing event coincidence analysis and the maximum coincidence rate, we quantified the grasslands’ responses to drought events. Our findings indicate a significant upward trend in SIF across all grassland types over the past two decades, while NDVI and soil moisture levels remained relatively stable. Under drought conditions, the probability of grassland degradation ranged from 40% to 60%. Notably, desert grasslands exhibited a considerably slower response rate compared to other grassland types, while meadow grasslands responded the fastest to drought; however, all grassland types displayed a response delay of 1–2 months. When soil moisture levels fell below −1.8 standard deviations (STDs), a reversal in grassland response patterns was observed, particularly in meadow grasslands, which showed a substantial increase in response probability. At soil moisture levels below −2.4 STD, this probability stabilized at approximately 90%, significantly higher than that of other grassland types. These insights provide a vital basis for understanding and mitigating drought impacts on resilient grassland ecosystems under climate change.