ABSTRACT
The tumor microenvironment includes blood vessels， lymph， nerves， non-malignant cells， and their metabolites at and near the tumor lesion site， which interact with cancer cells and promote cancer progression. Rapid proliferation of cancer cells increases oxygen consumption， or abnormalities in the structure and function of blood vessels in solid tumors lead to a decrease in oxygen supply， forming a hypoxia microenvironment. The existence of a hypoxia microenvironment is a typical pathophysiological feature of locally advanced solid tumors， widely present in various types of human malignant tumors. Hypoxia microenvironment is a sign of tumor microenvironment and an important and complex system in the breast tumor microenvironment. Its formation and development are closely related to the growth of breast cancer， occupying an important position in the research and treatment of breast cancer. With its advantages of multiple pathways and multiple targets， the effective monomer and compound of traditional Chinese medicine can better regulate the hypoxia microenvironment of breast cancer， inhibit the proliferation， invasion， and metastasis of breast cancer cells in the hypoxia environment， induce apoptosis， reverse their drug resistance， intervene in the metabolic reprogramming of breast cancer cells in the hypoxia environment， and inhibit their angiogenesis， thereby improving the quality of life of patients to a certain extent and prolonging the survival cycle of patients. This paper first summarized and discussed the effects of hypoxia microenvironment on proliferation， invasion， metastasis， drug resistance， immune function， metabolic reprogramming， non-coding RNA， iron death， and autophagy of breast cancer cells， which affected the occurrence and development of breast cancer， and it elaborated the mechanism behind it. Then， the paper elucidated the regulatory effect and mechanism of targeting the hypoxia microenvironment based on the two modes of effective monomer and compound of traditional Chinese medicine， so as to analyze and extract the deficiencies and directions of traditional Chinese medicine in regulating the hypoxia microenvironment and provide a theoretical reference for the effective treatment of breast cancer.
ABSTRACT
Cerebral ischemia/reperfusion injury （CIRI） is a complex cascade reaction process in which the blood flow and oxygen supply of brain tissue in the infarcted area recover after cerebral ischemia， resulting in secondary injury of ischemic brain tissue. At present， thrombolysis as soon as possible and restoration of cerebral blood supply are still the only strategies for the treatment of stroke， but a considerable number of patients' symptoms will be more serious after reperfusion， making patients face adverse outcomes such as neurological function injury and even death and seriously affecting the quality of life and safety of patients. Therefore， an in-depth exploration of the mechanism and treatment strategy of CIRI has important clinical significance. The phosphatidylinositol 3- kinase （PI3K）/protein kinase B （Akt） signaling pathway is one of the classic anti-apoptosis/reproductive-promoting signal transduction pathways， which is responsible for cell proliferation， growth， and differentiation. It is the key cascade signaling pathway of CIRI， located at the core site in many mechanisms such as mitochondrial disorder， apoptosis， autophagy， oxidative stress， and inflammation. It is closely related to the occurrence and development of CIRI. Traditional Chinese medicine has been used in the clinical treatment of stroke and its complications for thousands of years， and the clinical effect of traditional Chinese medicine in the prevention and treatment of CIRI has been affirmed by a large number of research results in recent years. It is further clarified that the monomers， active components， and their compound prescriptions of traditional Chinese medicine can directly or indirectly regulate the PI3K/Akt signaling pathway by virtue of the biological advantages of multi-targets， multi-components， and multi-pathways and play an overall protective role in CIRI. By analyzing the related research progress of traditional Chinese medicine in China and abroad in recent years， the authors summarized the role and mechanism of regulating the PI3K/Akt signaling pathway in the prevention and treatment of CIRI， so as to provide further theoretical basis for the study of the mechanism of clinical prevention and treatment of CIRI.