Objective To introduce the inflammatory microenvironment and epithelial-mesenchymal transition process of hepatocellular carcinoma, and review the relationship between them. Methods Domestic and international literatures were collected to summary the relationship between epithelial-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma. Result Many inflammatory factors and viral gene encoding proteins in the inflammatory microenvironment play an important role in the process of epithelial-mesenchymal transition in hepatocellular carcinoma. Conclusions The inflammatory microenvironment of hepatocellular carcinoma is an indispensable role in the process of epithelial-mesenchymal transition. The inhibition and treatment of inflammatory microenvironment may play a more active role in the control of tumor invasion and metastasis.
Objective To investigate relationship between hypoxia microenvironment and occurrence and development of hepatocellular carcinoma (HCC). Method The relevant literatures on researches of the relationship between the hypoxic microenvironment and the HCC were review and analyzed. Results The hypoxia microenvironment played an important role in inducing the drug resistance and angiogenesis of the HCC cells, and it was an important factor of affecting the ability of tumor metabolism, invasion, and migration. The hypoxia microenvironment could up-regulate the expression of hypoxia-inducible factors (HIFs) and promote its transcriptional activity, promote the expression of the vascular endothelial growth factor gene, and regulate the neovascularization in the tumor. Among them, the HIF-1α played a major role in regulating the angiogenesis, immune escape, tumor invasion and metastasis-related gene expression, participating in the glycolysis, regulating lysyl oxidase 2 and thus regulated epithelial-mesenchymal transition, then promoted the invasion and metastasis of the HCC; HIF-2α was a key regulator of the malignant phenotype involving in the cell proliferation, angiogenesis, apoptosis, metabolism, metastasis, and resistance to chemotherapy. The hypoxia microenvironment posed some difficulties for the treatment of HCC, but it was also a potential therapeutic breakthrough. Conclusion Hypoxia microenvironment can promote invasion and metastasis of HCC through various mechanisms, which provides new targets and strategies for clinical treatment of HCC.
ObjectiveTo summarizes the mechanisms of carcinogenesis of colorectal cells, the occurrence and development of cancer cells, and their interactions with the tumor niche of colorectal cancer (CRC) from the perspective of the tumor niche, exploring new ideas for the prevention, diagnosis, and treatment of CRC. MethodThe relevant literature at home and abroad in recent years on the researches of mechanism of the occurrence and development of CRC and its relation with the tumor niche of CRC was searched and reviewed. ResultsThe theory of tumor ecology indicates that the human normal body can be regarded as a relatively closed and perfect ecosystem. Each normal tissue and organ within the body represent a niche in this ecosystem, which interact, affect, and symbiotically coexist with each other, forming a dynamic ecological balance. Tumor cells, being a “new species” distinct from normal tissue cells, “invade” the ecological system of the normal body under specific conditions and interact with the surrounding microenvironment, which is defined as the tumor niche. Analysis of current literature retrieved from the perspective of the tumor niche suggested that, although genetic factors are involved in the carcinogenesis of colorectal cells, the majority of such carcinogenesis stems from the continuous stimulation of the colorectal niche. Current research primarily focuses on the conclusion that the carcinogenesis of colorectal cells is associated with factors such as chronic inflammatory response, intestinal microorganisms, oxidative stress, and pyroptosis. After carcinogenesis and the eventual formation of CRC, the growth of cancer cells and tissues first requires breaching the defense of the immune system in the colorectal niche. Immune cells in the immune system play a crucial role in the tumor niche during the occurrence and development of CRC. ConclusionsThe proposal of the tumor niche concept enables researchers, when studying the mechanisms of tumor occurrence and development, to no longer merely focus on the tumor and its microenvironment. Instead, the tumor as a part of the body’s ecosystem was studied. Components of the tumor niche, such as chronic inflammatory responses, intestinal microorganisms, oxidative stress, pyroptosis, and immune system, have a significant impact on the mechanisms of carcinogenesis of most colorectal cells, as well as the occurrence and development of cancer cells. These factors influence the progression of CRC in various aspects.
ObjectiveTo analyze the correlation between the molecular biological information of SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) and its clinical prognosis, and to explore the spatial features and molecular mechanisms of interactions between cells in the tumor microenvironment (TME) of SMARCA4-dNSCLC. MethodsUsing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), this study conducted functional enrichment analysis on differentially expressed genes (DEGs) in SMARCA4-dNSCLC and depicted its genomic variation landscape. Through weighted gene co-expression network analysis (WGCNA) and a combination of 10 different machine learning algorithms, patients in the training group were divided into a low-risk group and a high-risk group based on a median risk score (RiskScore). A corresponding prognostic prediction model was established, and on this basis, a nomogram was constructed to predict the 1, 3, and 5-year survival rates of patients. K-M survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model. External datasets from GEO further validated the prognostic value of the prediction model. In addition, we also evaluated the immunological characteristics of the TME of the prognostic model. Finally, using single-cell RNA sequencing (scRNA-seq) and spatial transcriptome (ST), we explored the spatial features of interactions between cells in the TME of SMARCA4-dNSCLC, intercellular communication, and molecular mechanisms. ResultsA total of 56 patients were included in the training group, including 38 males and 18 females, with a median age of 62 (56-70) years. There were 28 patients in both the low-risk and high-risk groups. A total of 474 patients were included in the training group, including 265 males and 209 females, with a median age of 65 (58-70) years. A risk score model composed of 8 prognostic feature genes (ELANE, FSIP2, GFI1B, GPR37, KRT81, RHOV, RP1, SPIC) was established. Compared with patients in the low-risk group, those in the high-risk group showed a more unfavorable prognostic outcome. Immunological feature analysis revealed differences in the infiltration of various immune cells between the low-risk and high-risk groups. ScRNA-seq and ST analyses found that interactions between cells were mainly through macrophage migration inhibitory factor (MIF) signaling pathways (MIF-CD74+CXCR4 and MIF-CD74+CD44) via ligand-receptor pairs, while also describing the niche interactions of the MIF signaling pathway in tissue regions. ConclusionThe 8-gene prognostic model constructed in this study has certain predictive accuracy in predicting the survival of SMARCA4-dNSCLC. Combining the ScRNA-seq and ST analyses, cell-to-cell crosstalk and spatial niche interaction may occur between cells in the TME via the MIF signaling pathway (MIF-CD74+CXCR4 and MIF-CD74+CD44).
ObjectiveTo explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). MethodsThe Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. GO, KEGG, and GSEA enrichment analyses were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients' 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. ResultsDifferentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. ConclusionThe prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.
ObjectiveTo summarize the relationship between integrins, tumor metabolism, and tumor cells with pancreatic stellate cells in the tumor microenvironment, in order to provide targets and ideas for the treatment of pancreatic ductal adenocarcinoma.MethodTo review the literatures on pancreatic stellate cells, integrins, and amino acid metabolism as therapeutic targets for pancreatic ductal adenocarcinoma in the domestic and overseas.ResultsThe drug research for pancreatic ductal adenocarcinoma was currently under vigorous development, but remain in the animal and clinical test stage. As a new therapeutic protein, ProAgio could inhibit the expression of integrin αvβ3, activation and secretion of pancreatic stellate cells, and alanine metabolism in the microenvironment of pancreatic ductal adenocarcinoma, so as to achieve the dual effects of anti-fibrosis and anti-tumor.ConclusionsThe roles of activated pancreatic stellate cells, ProAgio, integrin αvβ3, and alanine metabolism in pancreatic ductal adenocarcinoma have been partially elucidated, but the specific mechanism still needs further investigation and may become a completely new therapeutic target someday.
Objective To study the influence of different mechanical environments on repair cartilage defect with marrow mesenchymal stem cells as seed cells. Methods The rabbit marrow mesenchymal stem cells were isolated and cultured. The cartilage defects were repaired by autologous tissue engineered cartilage with the marrow mesenchymal stem cells as seed cells. Fifteen rabbits with cartilage defect were divided into 3 groups: dislocation group with cell-free scaffold(controlgroup), dislocation group with cartilaginous construct and normal mechanical environment group with cartilaginous construct. The repaired tissue was harvested and examined 6 weeks postoperatively. Results The repair tissue in normal mechanical environment group with cartilaginous construct showed cartilage-like tissue in superficial layer and subchondral bone tissue in deep layer 6 weeks postoperatively. The defect was filled with bone tissue in dislocation group with cartilaginous construct 6 weeks postoperatively. The surrounding normal cartilage tissue showed vascular invasion from subchondral area and the concomitant thinningof the normal cartilage layer. The cartilaginous construct left in the femoral trochlea groove formed hyaline cartilage-like tissue. The defect was repaired byfibrous tissue in control group. Conclusion The repaired tissue by tissue engineered cartilage with marrow mesenchymal stem cells as seed cells showed the best result in normal mechanical environment group, which indicates that it will be essential for the formation and maintenance of tissue engineered cartilage to keep the normal mechanical stress stimulus.
Stem cells have been regarded with promising application potential in tissue engineering and regenerative medicine due to their self-renewal and multidirectional differentiation abilities. However, their fate is relied on their local microenvironment, or niche. Recent studied have demonstrated that biophysical factors, defined as physical microenvironment in which stem cells located play a vital role in regulating stem cell committed differentiation. In vitro, synthetic physical microenvironments can be used to precisely control a variety of biophysical properties. On this basis, the effect of biophysical properties such as matrix stiffness, matrix topography and mechanical force on the committed differentiation of stem cells was further investigated. This paper summarizes the approach of mechanical models of artificial physical microenvironment and reviews the effects of different biophysical characteristics on stem cell differentiation, in order to provide reference for future research and development in related fields.
Objective To summarize the research progress of magnetic resonance quantitative technique in the iron overload of the abdominal parenchyma organ. Methods By reviewing the related literatures domesticly and abroad, the present status and progress of abdominal magnetic resonance quantitative technique and other examinations in the study of iron overload were analyzed. Results MRI multi-sequence examination technique had changed the research model of iron overload in different organs, and had important clinical significance in imaging diagnosis of abdominal parenchyma organ damage. so far, many techniques of MRI had been used in detection of iron overload, which included signal intensity measurements(including signal intensity ratio and signal intensity difference of positive and negative phases), T2/R2 measurements, T2*/R2* measurements, Dixon and its derivatization, ultrashort echo time technique and susceptibility weighted imaging (including conventional susceptibility weighted imaging and quantitative magnetic sensitive imaging). Conclusion Magnetic resonance quantitative examination technique is expected to be the first choice for detection of hepatic iron overload, and can improve the early detection rate of iron overload pancreatic damage.
ObjectiveTo review the relative researches about mechanical stimulation of stem cells differentiation in stem cells microenvironment in vitro. MethodsThe recent related literature about stem cells differentiation in vitro was reviewed and summarized. ResultsThe mechanical loads (including shear stress, mechanical strain, and stress), substrates stiffness, substrates nanotopography, and cell shape were the 4 important aspects of mechanical factors regulating stem cells differentiation. The mechanical stimulation can simulate the in vivo microenvironment, which can alter the size, shape, alignment, and differentiation state of stem cells, can change the expression of their differentiation markers, and can affect the lineage commitment of stem cells. ConclusionMechanical stimulation play an important role in regulating stem cells differentiation and cells morphology in addition to chemical and biological factors.