Objective The bone marrow mesenchymal stem cells (BMSCs) have the capacity to differentiate into insul in-producing cells (IPCs) in vitro. However, low differentiation efficiency and poor maturity are the main obstacles. To investigate the feasibil ity of BMSCs differentiation into IPCs in diabetic pancreatic microenvironment of pigs. Methods BMSCs were isolated and purified from the bone marrow of a 4-week-old male pig. Fifteen female pigs (aged 8 to 10 weeks, weighing 8 to 10 kg) were randomly divided into 3 groups: normal control group (group A, n=5), diabetic control group (group B, n=5), and BMSCs transplanted group (group C, n=5). The pigs of groups B and C were treated by auris vein injections of styeptozocin and alloxan for 3 days to induce diabetes mell itus (DM) model, whose blood glucose level 2 days all greater than 17 mmol/L was successful DM model. A total of 1.1 mL of the 3rd passage BMSCs labeled with enhanced green fluorescent protein (EGFP), with cell density of 5 × 107/ mL, were injected into subcapsular pancreas of group C at multi ple points, normal saline at the same dosage into those of groups A and B. After 30 days of monitoring blood glucose, the histological analysis of islet number and size were done; the immunofluorescence staining was used to detect the protein expression of insul in in the new-formed islets. The EGFP+ cells were collected from the sections using laser-capture microdissection; RT-PCR was used to detect insulin mRNA and pancreatic and duodenal homeobox factor 1 (PDX1) mRNA expressions from EGFP+ cells, and the insul in and sexdetermining region of the Y chromosome (SRY) genes were detected by fluorescence in situ hybridization (FISH). Results The blood glucose level decreased significantly in group C when compared with that in group B from 18 days and gradually decreased with time (P lt; 0.05). The histological observation showed that the number of islets was increased significantly in group C when compared with that in group B (10.9 ± 2.2 vs. 4.6 ± 1.4, P lt; 0.05), and there was no significant difference when compared with that in group A (10.9 ± 2.2 vs.12.6 ± 2.6, P gt; 0.05). The size of new-formed islets in group C was significantly smaller than that in group A [(47.2 ± 19.6) μm vs. (119.6 ± 27.7) μm, P lt; 0.05]. The immunofluorescence staining showed that new-formed islets of group C expressed insulin protein. RT-PCR showed that the microdissected EGFP+ cells of group C expressed insulin mRNA and PDX-1 mRNA. FISH showed that the new-formed islet cells of group C contained SRY gene in Y chromosome and insulin double positive cells. Conclusion BMSCs can differentiate into IPCs in diabetic pancreatic microenvironment of pigs.
N,N-Dimethylglycine (DMG) is a glycine derivative, and its sodium salt (DMG-Na) has been demonstrated to possess various biological activities, including immunomodulation, free radical scavenging, and antioxidation, collectively contributing to the stability of tissue and cellular functions. However, its direct effects and underlying mechanisms in wound healing remain unclear. In this study, a full-thickness excisional wound model was established on the dorsal skin of mice, and wounds were treated locally with DMG-Na. Wound healing progression was assessed by calculating wound closure rates. Histopathological analysis was conducted using hematoxylin-eosin (HE) staining, and keratinocyte proliferation, migration, and differentiation were evaluated using CCK-8 assays, scratch wound assays, and quantitative reverse transcription PCR (qRT-PCR). Inflammation-related cytokine expression in keratinocytes was analyzed via ELISA and qRT-PCR. Results revealed that DMG-Na treatment significantly accelerated wound healing in mice and improved overall wound closure quality. The wound healing rates on days 3, 6, and 9 were 49.18%, 68.87%, and 90.55%, respectively, with statistically significant differences compared to the control group (P<0.05). DMG-Na treatment downregulated the mRNA levels of keratinocyte differentiation markers while enhancing cell proliferation and migration (P<0.05). Furthermore, DMG-Na decreased the secretion of LPS-induced keratinocyte inflammatory cytokines, including IL-1β, IL-6, IL-8, TNF-α, and CXCL10 (P<0.05). These findings indicate that DMG-Na regulates inflammatory responses and promotes keratinocyte proliferation and migration, thereby facilitating the healing of skin wounds.
Inhibiting metastasis is the key to the treatment of malignant tumors. During the development of tumors, the microenvironment plays a significant role, and hypoxia is one of its important characteristics. Exosomes, as an important component of the microenvironment, connect tumor cells with the hypoxic microenvironment and mediate information exchange between cells. Tumor cells secrete more exosomes than normal cells, and hypoxia further stimulates their release. Hypoxia-induced tumor-derived exosomes carry stable genetic material and play key regulatory roles in promoting tumor proliferation, establishing a pre-metastasis microenvironment, and accelerating angiogenesis. This article comprehensively reviews the mechanisms by which tumor-derived exosomes regulate tumor proliferation and metastasis in a hypoxic microenvironment, which has potential clinical significance.
ObjectiveTo summarize the regulating mechanism of microRNA in tumor microenvironment. MethodThe literatures about the studies on the mechanism regulated by microRNA for tumor microenvironment were reviewed according to the results searched from PubMed in recent years. ResultsmicroRNA might be participated in regulation of tumor microenvironment factors such as hypoxia-inducible factor, tumor associated fibroblasts, extracellular matrix, which leaded to a change in biological behavior of tumor cells by reforming the microenviroment. ConclusionsmicroRNA has been participated in regulating many factors of tumor microenvironment. The change of neoplastic microenvironment has been recognized to play a critical role in the development of cancer. Therefore revealing microRNA mechanism for tumor microenvironment could not only help exploring the biological behavior of tumor cells, but also come an important insight for new means of diagnosis and treatment of cancer.
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.
Mechanical signal transduction are crucial for chondrocyte in response to mechanical cues during the growth, development and osteoarthritis (OA) of articular cartilage. Extracellular matrix (ECM) turnover regulates the matrix mechanical microenvironment of chondrocytes. Thus, understanding the mechanotransduction mechanisms during chondrocyte sensing the matrix mechanical microenvironment can develop effective targeted therapy for OA. In recent decades, growing evidences are rapidly advancing our understanding of the mechanical force-dependent cartilage remodeling and injury responses mediated by TRPV4 and PIEZOs. In this review, we highlighted the mechanosensing mechanism mediated by TRPV4 and PIEZOs during chondrocytes sensing mechanical microenvironment of the ECM. Additionally, the latest progress in the regulation of OA by inflammatory signals mediated by TRPV4 and PIEZOs was also introduced. These recent insights provide the potential mechanotheraputic strategies to target these channels and prevent cartilage degeneration associated with OA. This review will shed light on the pathogenesis of articular cartilage, searching clinical targeted therapies, and designing cell-induced biomaterials.
ObjectiveTo summarize the relationship between exosomes and the occurrence and development of gastrointestinal cancer.MethodsThrough online database, we collected the literatures about the relationship between exosomes and the development of gastrointestinal cancer at home and abroad, and then made an review.ResultsExosomes secreted by gastrointestinal cancer cells were related to tumorigenesis, tumor cell survival, chemoresistance, and early metastasis. Exosomes could play the role of information transmission, and regulation of cell physiology and pathological process in the development of gastrointestinal cancer through a variety of intercellular binding ways, and affectted the occurrence and development of gastrointestinal cancer via epigenetic regulation and tumor related signal transduction mechanism. They had been proved to be biomarkers, targets, and drug carriers for the treatment of gastrointestinalcancer.ConclusionIt is a new way to explore the molecular mechanism of exosomes in the development of gastrointestinal cancer.
ObjectiveTo understand the single-cell RNA sequencing (scRNA-seq) and its research progress in the tumor microenvironment (TME) of breast cancer, in order to provide new ideas and directions for the research and treatment of breast cancer. MethodThe development of scRNA-seq technology and its related research literature in breast cancer TME at home and abroad in recent years was reviewed. ResultsThe scRNA-seq was a quantum technology in high-throughput sequencing of mRNA at the cellular level, and had become a powerful tool for studying cellular heterogeneity when tissue samples were fewer. While capturing rare cell types, it was expected to accurately describe the complex structure of the TME of breast cancer. ConclusionsAfter decades of development, scRNA-seq has been widely used in tumor research. Breast cancer is a malignant tumor with high heterogeneity. The application of scRNA-seq in breast cancer research can better understand its tumor heterogeneity and TME, and then promote development of personalized diagnosis and treatment.
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.