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.
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.
Abstract To study the regulation of growth and proliferation of tissue-repair cell from wound microenvironment, the effects of wound fluid (WF) on the growth and proliferation of wound fibroblast were studied in vitro. Thirty rats were divided into 6 groups. On the back of every rat, an incision of 0.5～1.0cm was performed a subcutaneous sac was made by blunt dissection. A piece of sponge was put in, and the wound was sutured. After 1,3,7,9,11,15 days, one group of the rats were sacrificed respectively, and WF was collected from the sponge. Two kinds of medium were made with each WF: 1640+1%FCS+10%WF and1640+10%FCS+10%WF. After 48 hours incubation with newly prepared wound fibroblasts, the growth of the cells was observed. It was shown that (1) Under 1%FCS, WFfrom1,3,7 days stimulated cell proliferation, and WF from 9,11,15 days caused cell death. (2) Under 10%FCS, WF from 9,11,15 days inhibited cell growth. It was suggested that the wound microenvironment stimulated the fibroblasts to proliferate for one week after injury, and beyond that further growth seemed to be arrested, and that there might be some growth inhibitory factors present in the microenvironmentduring the late stage of wound healing.
Acoustic environment is an important part of the overall environment of a hospital. Acoustic environmental pollution will have varying degrees of impact on human physiology and psychology. Acoustic environmental pollution in outpatient clinics has become a major concern for visitors and medical staff. Exploring the causes of outpatient acoustic environment pollution and adopting active countermeasures are effective methods to control outpatient acoustic environment pollution. This article will review the current situation of acoustic environmental pollution in outpatient clinics and the impact of acoustic environmental pollution on medical staff and visitors, and analyze the common causes of outpatient acoustic environmental pollution based on actual conditions, and propose corresponding solutions for the corresponding causes. It aims to provide a reference for clinically effective control of acoustic environmental pollution in outpatient clinics.
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.
Idiopathic pulmonary fibrosis (IPF) is a progressive scar-forming disease with a high mortality rate that has received widespread attention. Epithelial mesenchymal transition (EMT) is an important part of the pulmonary fibrosis process, and changes in the biomechanical properties of lung tissue have an important impact on it. In this paper, we summarize the changes in the biomechanical microenvironment of lung tissue in IPF-EMT in recent years, and provide a systematic review on the effects of alterations in the mechanical microenvironment in pulmonary fibrosis on the process of EMT, the effects of mechanical factors on the behavior of alveolar epithelial cells in EMT and the biomechanical signaling in EMT, in order to provide new references for the research on the prevention and treatment of IPF.
ObjectiveTo review cancer associated fibroblasts(CAFs) and its role in the evolution of gastrointestinal neoplasms. MethodDomestic and international publications in relation to CAFs and its role in the evolution of gastrointestinal neoplasms were collected and reviewed. ResultsIn the gastrointestinal cancers, as the largest number and the most important stromal cells of the tumor microenvironment, CAFs induce the homeostasis of cell microenviron-ment out of balance, promote the remodeling of the tumor metabolism and extracellular matrix(ECM), and thus impulse the generation, proliferation, invasion and metastasis of the tumor by secreting different kinds of cytokines. ConclusionsThe key role CAFs playing in the tumor generation and evolution makes themselves and the multiple relatively specific molecules they secrete a new target for prognosis and targeted therapy, and this gives us a new idea for the combined treatment of gastrointestinal tumor or any other tumors.
ObjectiveTo introduce the research status of the immunoregulation function of cancer-associated fibroblasts (CAFs) in tumor microenvironment.MethodThe literatures in recent years on the studies of role of CAFs in the regulation of immune response in the tumor microenvironment were collected and summarized.ResultsThe CAFs played a critical role as the components of the tumor microenvironment. The CAFs could product various growth factors and cytokines that were contributed to the immunoregulation including the polarization of the immune cells and the regulation of the function of immune cells in the tumor microenvironment and eventually resulted in the carcinogenesis, tumor progression, invasion, metastasis and therapy resistance.ConclusionCAFs play a significant role in the immunoregulation in tumor microenvironment, but as a potential target for breast cancer, more studies are still needed to discover the specific markers, heterogeneity, and key signaling pathways.
ObjectiveTo explore the effects of hypoxia inducible factor-1 alpha (HIF-1α) on the reverse differentiation of hepatocellular carcinoma cells into liver cancer stem cells, and the maintenance of malignant biological behavior in hypoxic environment.MethodsCD133-negative cells in HepG2 cells were separated by immunomagnetic beads and divided into two groups. The cells of siRNA group were transfected with siRNA-HIF-1α to silence the expression of HIF-1α gene, while cells of the blank control group did not transfect any siRNA fragments. The two groups of cells were cultured under normal and hypoxic conditions respectively. MTT, cloning and Transwell chamber experiments were used to detect the proliferation and invasion ability of cells. Western blot and real-time PCR (RT-PCR) were used to detect the expressions of HIF-1α, CD133, CD90, and CD44 protein and mRNA in cells.ResultsMTT results showed that the cell proliferation rate increased with the prolongation of hypoxia in four groups. Compared with the blank control group at 24, 32, 40, and 48 hours, the cell proliferation rate decreased significantly after siRNA-HIF-1a transfection, on both two kinds of cultured conditions (P<0.05). The results of plate cloning experiment showed that the number of cell-forming clones increased significantly after hypoxic culture (there were significant differences between the transfected normoxic group and transfected hypoxic group, blank control normoxic group and blank control hypoxic group, P<0.05); and the formation of transfected hypoxic condition group at the same time of hypoxia was also significant (P<0.05). The number of clones were significantly less than that of the blank control group at the hypoxic condition (P<0.05). Transwell lab experiment showed that after hypoxic culture, the number of cells migrated to the inferior chamber in the transfection group was significantly reduced compared with that of the blank control group (P<0.05). Western blot and RT-PCR results showed that the expression levels of HIF-1α protein and tumor stem cell markers (CD133, CD90, and CD44 protein) in the blank control hypoxic condition group were significantly higher than those in the other three groups (P<0.05); after siRNA-HIF-1a transfection, HIF-1α mRNA and tumor stem cell markers mRNA (CD133, CD90, and CD44 mRNA) in the transfected hypoxic condition group were significantly lower than those in the transfected normal condition group and the blank control normal condition group (P<0.05).ConclusionsIn hypoxia environment, HIF-1α can promote hepatocellular carcinoma cells to differentiate into liver cancer stem cells and enhance their malignant biological behavior.
ObjectiveTo investigate the effects of three-dimensional (3D) printed Ti6Al4V-4Cu alloy on inflammation and osteogenic gene expression in mouse bone marrow mesenchymal stem cells (BMSCs) and mouse mononuclear macrophage line RAW264.7.MethodsTi6Al4V and Ti6Al4V-4Cu alloys were prepared by selective laser melting, and the extracts of the two materials were prepared according to the biological evaluation standard of medical devices. The effects of two kinds of extracts on the proliferation of mouse BMSCs and mouse RAW264.7 cells were detected by cell counting kit 8 method. After co-cultured with mouse BMSCs for 3 days, the expression of osteogenesis- related genes [collagen type Ⅰ (Col-Ⅰ), alkaline phosphatase (ALP), Runx family transcription factor 2 (Runx-2), osteoprotegerin (OPG), and osteopontin (OPN)] were detected by real-time fluorescence quantitative PCR. After co-cultured with mouse RAW264.7 cells for 1 day, the expressions of inflammation-related genes [interleukin 4 (IL-4) and nitric oxide synthase 2 (iNOS)] were detected by real-time fluorescence quantitative PCR, and the supernatants of the two groups were collected to detect the secretion of vascular endothelial growth factor a (VEGF-a) and bone morphogenetic protein 2 (BMP-2) by ELISA. The osteogenic conditioned medium were prepared with the supernatants of the two groups and co-cultured with BMSCs for 3 days. The expressions of osteogenesis-related genes (Col-Ⅰ, ALP, Runx-2, OPG, and OPN) were detected by real-time fluorescence quantitative PCR.ResultsCompared with Ti6Al4V alloy extract, Ti6Al4V-4Cu alloy extract had no obvious effect on the proliferation of BMSCs and RAW264.7 cells, but it could promote the expression of OPG mRNA in BMSCs, reduce the expression of iNOS mRNA in RAW264.7 cells, and promote the expression of IL-4 mRNA. It could also promote the secretions of VEGF-a and BMP-2 in RAW264.7 cells. Ti6Al4V-4Cu osteogenic conditioned medium could promote the expressions of Col-Ⅰ, ALP, Runx-2, OPG, and OPN mRNAs in BMSCs. The differences were all significant (P<0.05).Conclusion3D printed Ti6Al4V-4Cu alloy can promote RAW264.7 cells to secret VEGF-a and BMP-2 by releasing copper ions, thus promoting osteogenesis through bone immune regulation, which lays a theoretical foundation for the application of metal prosthesis.