RESUMO
Cell death is a natural biological process that occurs in living organisms. Since 1963, extensive research has shed light on the occurrence, progress, and final outcome of cell death. According to different cell phenotypes, it is classified into different types, including apoptosis, pyroptosis, necroptosis, autophagy, ferroptosis, cuproptosis, and so on. However, regardless of the form of cell death, what we ultimately expect is the disappearance of abnormal cells, such as tumor cells, while normal cells survive. As a result, it is vital to investigate the details of cell death, including death triggers, potent regulators, and executioners. Although significant progress has been made in understanding molecular pathways of cell death, many aspects remain unclear because of the complex regulatory networks in cells. Among them, the phosphoinositide-3-kinase (PI3K)/protein kinase B(AKT) pathway is discovered to be a crucial regulator of the cell death process. AKT, as a proto-oncogene, has become a major focus of attention in the medical community due to its role in regulating a multiplicity of cellular functions counting metabolism, immunity, proliferation, survival, transcription, and protein synthesis. Here, we explored the connection between the PI3K/AKT pathway and cell death, aiming to enhance our comprehension of the mechanism underlying this process. Such knowledge may pave the way for the subsequent development of more effective disease treatments, such as finding suitable targets for drug intervention.
Assuntos
Fosfatidilinositol 3-Quinase , Proteínas Proto-Oncogênicas c-akt , Morte Celular Regulada , Apoptose , Proliferação de Células , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , HumanosRESUMO
Use of live laboratory animals is essential in the process of functional experimentation teaching. There are ethical problems, such as poor experimental environment, non-standard operation, and neglect of animal rights in experimental teaching. As an important basic course in life science education, functional experimentation should establish the correct ethics of use of laboratory animals. The welfare of laboratory animals has become one of the frontier directions of medical ethics research. The "4R" principle of animal welfare is based on the principles of reduction, replacement, refinement, and responsibility, which may provide a way to solve ethical problems in the teaching and research activities of functional experimentation. In addition to receiving relevant knowledge and education, laboratory animal practitioners and students in functional experimentation teaching should consciously abide by relevant regulations and rules and actively follow the "4R" principles. Animal ethics education is reflected in all teaching and research activities. Based on the principle of "4R" and the premise of guaranteeing teaching objectives, virtual simulation experiment teaching is a great supplement to functional experimentation. In teaching, medical ethics education should be strengthened to cultivate the consciousness of respecting the life of experimental animals, and awareness of laboratory animal ethics should be improved among teachers and students of functional experimentation to further promote ideological and political education in colleges and universities. This brief summary analyzes the general situation of animal ethics in functional experimentation in China based on the principle of "4R" and provides certain references and support for course teaching and training.
Assuntos
Experimentação Animal , Animais , Humanos , Bem-Estar do Animal , Direitos dos Animais , Animais de Laboratório , EstudantesRESUMO
BACKGROUND: Traumatic brain injury (TBI) is a common complication of acute and severe neurosurgery. Remodeling of N6-methyladenosine (m6A) stabilization may be an attractive treatment option for neurological dysfunction after TBI. In the present study, we explored the epigenetic methylation of RNA-mediated NLRP3 inflammasome activation after TBI. METHODS: Neurological dysfunction, histopathology, and associated molecules were examined in conditional knockout (CKO) WTAP[flox/flox, Camk2a-cre], WTAPflox/flox, and pAAV-U6-shRNA-YTHDF1-transfected mice. Primary neurons were used in vitro to further explore the molecular mechanisms of action of WTAP/YTHDF1 following neural damage. RESULTS: We found that WTAP and m6A levels were upregulated at an early stage after TBI, and conditional deletion of WTAP in neurons did not affect neurological function but promoted functional recovery after TBI. Conditional deletion of WTAP in neurons suppressed neuroinflammation at the TBI early phase: WTAP could directly act on NLRP3 mRNA, regulate NLRP3 mRNA m6A level, and promote NLRP3 expression after neuronal injury. Further investigation found that YTH domain of YTHDF1 could directly bind to NLRP3 mRNA and regulate NLRP3 protein expression. YTHDF1 mutation or silencing improved neuronal injury, inhibited Caspase-1 activation, and decreased IL-1ß levels. This effect was mediated via suppression of NLRP3 protein translation, which also reversed the stimulative effect of WTAP overexpression on NLRP3 expression and inflammation. CONCLUSION: Our results indicate that WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after TBI and that WTAP/m6A/YTHDF1 downregulation therapeutics is a viable and promising approach for preserving neuronal function after TBI, which can provide support for targeted drug development.
RESUMO
Cervical cancer is a common malignant tumor and a leading cause of death in women worldwide. It plays a crucial role in tumorigenesis and progression of cervical cancer. A total of 1606 references on inflammation in cervical cancer were retrieved from the Web of Science Core Collection and visual analysis was performed using VOSviewer. Inflammation in cervical cancer has attracted the attention of researchers. Even though China is the country that publishes the most papers, with the most of the top-ranking institutions, there is no extensive collaboration and exchange of papers by Chinese scholars. PLOS One is a popular journal on inflammation in cervical cancer. Instead, authors from other countries perform better, for example, the Sjoerd H. Van Der Burg is the most widely cited author and "M2 macrophages induced by prostaglandin E2 and IL-6 from cervical carcinoma are switched to activated M1 macrophages by CD4â +â Th1 cells" (Moniek Heusinkveld, Leiden University Medical Center) is the most cited article of inflammation in cervical cancer. Keywords associated with "apoptosis," "HPV," "NF-κB," and "oxidative stress have been used in many studies, and keywords associated with "apoptosis," "human papillomavirus (HPV)," "NF-κB," and "oxidative stress" are involved in many studies, and there may be more research ideas in the future. From the perspective of precision medicine, more substantive research articles can promote scientific value, strengthen communication and cooperation, produce more extensive research results, and greatly promote the clinical diagnosis and treatment of cervical cancer. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , NF-kappa B , Bibliometria , InflamaçãoRESUMO
In this study, we evaluated the impact of preoperative high mobility group box 1 (HMGB1) on myocardial injury post-percutaneous coronary intervention.We evaluated 302 consecutive patients who underwent percutaneous coronary intervention. They were divided into equal tertiles based on their preoperative HMGB1 levels. Creatine kinase-MB and troponin I levels were measured at baseline, 8- and 24-hours after the procedure, while clinical outcomes were followed up for 1 year.The occurrence of post-procedural myocardial injury was significantly higher in the tertile comprising of patients with elevated HMGB1 levels. Moreover, these patients showed significantly higher post-procedural peak values of creatine kinase-MB and troponin I in comparison to patients with lower HMGB1 levels. Event-free survival was significantly associated with HMGB1 levels, with worst event-free survival in patients with elevated HMGB1 levels.Elevated preoperative HMGB1 was a predictor of myocardial injury after percutaneous coronary intervention, and was associated with the worst clinical outcomes during 1-year follow up.