Cell proliferation and differentiation
The law of "controllability of cell differentiation" is basically clarified, and "once cell differentiation is determined and divided" is questioned.
The traditional concept of "irreversibility after transformation" The experimental basis for the controllability of cell differentiation is put forward, which provides a theoretical basis for the treatment of "differentiated diseases (such as tumors)" for cloned animals by inducing cell differentiation and regulating the dedifferentiation of differentiated cells. (1) Embryonic spinal cord transplantation was established, and "Torni nucleus" was found in the cervical spinal cord of chicken embryo. The fate of excessive proliferation and predetermined automatic degeneration and death of nuclear cells can make the spinal cord survive and differentiate into a new preganglionic sympathetic column after transplantation into a suitable microenvironment (thoracic segment). It is proved that factors such as support and nutrition in the peripheral microenvironment can regulate cell differentiation (indicating that the expression of differentiation genes can be regulated).
(2) Chicken embryonic germ layer cells can change their differentiation types or become cancerous after virus infection under certain time and space conditions; Malignant tumor cells have the potential to be induced to differentiate into embryonic tissues in embryos.
(3) Under the control of two antagonistic antibody systems induced by medulla or cortex, the sexual differentiation ratio of differentiated gonads can be changed.
(4) Hematopoietic tumor cells (myeloma) can differentiate under the action of inducing differentiation agents (such as retinoic acid and DMSO) or regulatory factors (such as cytokines such as EDDF), which provides a theoretical basis for the induced differentiation of tumor cells.
Cell research
The paper of radioisotope autoradiography was published for the first time in China, which proved that the yolk ball of chicken embryo did not have the ability of protein's anabolism and self-renewal, and could not form cells (endoderm cells and blood islands of chicken embryo) by itself. This paper puts forward a negative view on Kimbosinskaya's life theory in the Soviet Union at that time, and expounds the proliferation law of endodermal cells and blood islands during the development of chicken embryos.
Study on cell regulation
The animal experimental research model, curative effect evaluation index and a set of multidisciplinary functional and morphological orientation, quantitative and qualitative detection methods of birth control drugs were established, and the anti-fertility and anti-fertility mechanisms of male reproduction in China and domestic birth control drugs such as gossypol and tripterygium wilfordii monomer were systematically studied. The mechanism of gossypol against spermatogenesis, its metabolic dynamics, toxicity, toxicology and genetic effects (carcinogenesis, teratogenicity and mutagenicity) in vivo were basically expounded, including its effects on sperm fertilization, pronuclear formation and haploid chromosome structure of human body. He has published more than 70 papers at home and abroad, and published the monograph "Experimental Study on Male Contraceptive Gossypol" (People's Health Publishing House, 1983, won the second prize of National Excellent Science and Technology Book). Won the second prize of 1986 and 1987 for scientific and technological progress of the Central Ministry of Health and the Family Planning Commission. He received financial support from WHO and the US Population Commission, and was invited to give special lectures, academic exchanges and scientific research cooperation in nine cities in the United States. In order to spread gossypol to the world and influence WHO and the United States Population Commission, it became the frontier subject of international male scientific research in 1970s and made contributions.
(1) discovered the target cell, target organelle, respiration, oxidative phosphorylation, energy system and molecular mechanism of LDH-C4 enzyme system unique to human sperm, put forward the hypothesis of drug target cell action site and the calculation rule of target cell position related to drug infertility time. Published more than 50 papers, which attracted the attention of international peers. Invited to be included in the international authoritative book Reproductive HEA 1th Health Care Progress, Volume 6, Male Ferti 1 ity and Its Regulation (1985, Y. T. lob 1 and E.S.E.Hafez, MTP Publishing Company Limited).
(2) The gossypol was labeled with 14C isotope for the first time in China, and the whole autoradiography technique was carried out in small animals (rats). The absorption, distribution and excretion of drugs in vivo (including feces, urine and exhalation), the calculation of half-life and the pharmacokinetics of metabolism, potassium (42K) metabolism and related Na-K- were expounded by combining the microscopic level and quantitative positioning technology of cells and electron microscope. He has published more than 20 papers and established 14C- gossypol research cooperation with three American universities.
Cellular mechanism and its research
The mystery of natural enucleation mechanism of mammalian red blood cells in terminal differentiation stage is basically clarified. This paper reveals the structural and functional differences between natural enucleated red blood cells (mammals) and non-enucleated red blood cells (birds) in the system development, and puts forward the hypothesis that natural enucleation is the result of systematic development and evolution. The experimental system of reticulocyte cytoplasmic hybridization model was established. It was found that there were a series of erythrocyte differentiation denucleation factors (EDDFs) in mammalian erythrocytes, which could regulate the programmed expression of genes related to terminal differentiation, nuclear condensation, natural enucleation and induced redifferentiation of hematopoietic (bone marrow) tumor cells. A series of cDNA sequences of the EDDF gene family have been cloned and registered in GenBank. Among them, genes related to nuclear chromatin concentration may be used as potential values to induce nuclear concentration (coagulation) of hematopoietic tumors to prevent malignant growth of tumor cells. More than 70 papers have been published in this research, and some achievements have won the second prize of the Central Ministry of Health 1988, 199 1 Scientific and Technological Progress, and the project is still in progress at the molecular level. He has given many lectures at the annual meeting of cell biology in Europe and America and the international symposium on morphology, and cooperated with the University of Hong Kong in scientific research. Two genes have applied for international patents from Hong Kong.
(1) A mammalian reticulocyte cytoplasmic hybridization model which can regulate the malignant growth of myeloma cells was established, as well as related cell mutants HL-60-AR and HI-60-AR/Nu, and hybrid cell lines BW-R, NS-R, SP-R, HL-R, Hmy-R and SP which can be used to screen anticancer drugs.
(2) Erythrocyte vimentin gene was inhibited in differentiated cells, and oncogene c-myc was also inhibited. Evolutionarily, it reveals the temporal and spatial differences of the growth and decline of this gene in natural enucleated (mammal) and non-enucleated (bird) red blood cell types, and the biphasic law of natural enucleation in mammals. The inhibition of vimentin fiber gene expression in mammalian cells is the key to natural enucleation, and the hypothesis that natural enucleation is the result of species evolution is put forward. It reveals the mystery of the material basis of natural enucleation of mammalian red blood cells and its evolutionary significance. After enucleation, hemoglobin is synthesized by globin gene mRNA in red blood cells and their cytoplasm, and becomes a terminal differentiated cell with full-time oxygen supply in blood circulation.
(3) It is found that there are a family of erythrocyte differentiation denucleation factors (EDDF) in mammalian erythrocytes, which can regulate the expression of terminal differentiation genes, induce nuclear chromatin condensation and enucleation, and reverse the malignancy of hematopoietic tumor cells. This factor can specifically activate globin gene expression in erythroid and non-erythroid myeloma cells, inhibit oncogene activity and promote cell differentiation. The purified EDDF active substance can specifically bind to the enhancer HS-2 sequence of β -globin gene and play the role of transcription factor. It has high activity of inhibiting growth and promoting differentiation of bone marrow tumor cell lines cultured in vitro.
(4) On this basis, six members of the related EDDF gene family with different terminal differentiation stages were cloned, which proved that they were new gene sequences that had not been reported in GenBank. According to the genes that can cause nuclear concentration and prevent cell division and proliferation, the theory of nuclear chromatin concentration and the new concept of tumor treatment that induces differentiation and inhibits malignant growth of tumor cells are put forward. * * * Published papers 10.