ABSTRACT
Alzheimer's disease is associated both with imbalances in Al3+ production and changes in viscosity in cells. Their simultaneous measurement could therefore provide valuable insights into Alzheimer's disease pathology. Their simultaneous measurement would therefore be of great value in investigating the pathological mechanism of Alzheimer's disease. We designed a fluorescent probe YM2T with AIE effect that is capable of selectively responding to Al3+ by fluorescence colormetrics and to viscosity by fluorescence "turn on" modes. Additionally, Al3+ and viscosity were simultaneously detected in PC12 cells using the low cytotoxic probe YM2T via blue and green fluorescence channels. More importantly, the YM2T probe was used to image mice with AD. Hence, the YM2T probe shows potential as a useful molecular instrument for studying the pathological impact of Al3+ and viscosity.
Subject(s)
Aluminum , Alzheimer Disease , Fluorescent Dyes , Optical Imaging , Alzheimer Disease/diagnostic imaging , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Viscosity , Animals , PC12 Cells , Mice , Aluminum/analysis , Aluminum/chemistry , Molecular Structure , Rats , Dose-Response Relationship, Drug , Structure-Activity Relationship , Disease Models, AnimalABSTRACT
The high mobility group protein B (HMGB) family (including HMGB1, HMGB2, HMGB3, and HMGB4) can regulate the mechanisms of DNA replication, transcription, recombination, and repair, and act as cytokines to mediate responses to infection, injury, and inflammation. HMGB1/2/3 has a high similarity in sequence and structure, while HMGB4 has no acidic C-terminal tail. Among them, HMGB3 can regulate the self-renewal and differentiation of normal hematopoietic stem cell population, but the decrease of its expression is easy to induce leukemia. Up-regulation of its expression promotes tumor development and chemotherapy resistance through a variety of mechanisms, and non-coding RNA can regulate to promote tumor cell proliferation, invasion, and migration and inhibit cancer cell apoptosis.
Subject(s)
Cell Proliferation , Drug Resistance, Neoplasm , HMGB3 Protein/metabolism , Neoplasm Proteins/metabolism , Neoplasms/metabolism , Humans , Neoplasms/pathologyABSTRACT
A counterbalance between immune cells and tumour cells is key to fighting tumours, and immune escape is an important mechanism for the survival of tumour cells in the body. Tumor cells and their cytokines impair the activity of T cells, NK cells, macrophages and other immune cells through various ways, and change the expression of their own surface antigens so as to avoid the clearance of the immune system. Changes in major histocompatibility complex molecules, high expression of programmed death-ligand 1, and the presence of immunosuppressive cells in the tumor microenvironment (TME) are main means by which tumors impair the function of immune cells. During the development of tumours of the digestive system, different mechanisms acting on tumour cells, the TME, and immune cells lead to immune escape and promote tumour progression. In this paper, the mechanisms of immune escape in tumour cells of the digestive system are reviewed to provide a theoretical basis for the immunotherapy of gastrointestinal tumours.
ABSTRACT
BACKGROUND: Clinical studies have shown that celecoxib can significantly inhibit the development of tumors, and basic experiments and in vitro experiments also provide a certain basis, but it is not clear how celecoxib inhibits tumor development in detail. METHODS: A literature search of all major academic databases was conducted (PubMed, China National Knowledge Internet (CNKI), Wan-fang, China Science and Technology Journal Database (VIP), including the main research on the mechanisms of celecoxib on tumors. RESULTS: Celecoxib can intervene in tumor development and reduce the formation of drug resistance through multiple molecular mechanisms. CONCLUSION: Celecoxib mainly regulates the proliferation, migration, and invasion of tumor cells by inhibiting the cyclooxygenases-2/prostaglandin E2 signal axis and thereby inhibiting the phosphorylation of nuclear factor-κ-gene binding, Akt, signal transducer and activator of transcription and the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9. Meanwhile, it was found that celecoxib could promote the apoptosis of tumor cells by enhancing mitochondrial oxidation, activating mitochondrial apoptosis process, promoting endoplasmic reticulum stress process, and autophagy. Celecoxib can also reduce the occurrence of drug resistance by increasing the sensitivity of cancer cells to chemotherapy drugs.