| Liquid crystal was firstly introduced to the field of biology in 1979,Brown GH and Wolken JJ systematically summarized the research progress of liquid crystal in biology in their work liquid crystal and biological structure.The researchers thought that there are four states in substance:gas-liquid-liquid crystal-solid（crystalline state）,among these liquid crystal shows high adaptability in the process of biological development because of its fluidity,self-assembly ordering and thermal sensitivity.The unique birefringence optical activity was formed due to the ordering of crystalline and liquid crystal.Liquid crystal has been widely reported in birds,fish and insect embryos.Recently,a tubular liquid crystal network structure has also been found in process of human stem cells differentiation into embryoids,which similar to original vascular network structure.Researches thought that one function of liquid crystal lipid droplets maybe providing energy in embryos stage.The concentric multilayer spherical structure of liquid crystals can provide organic templates for inducing crystal formation and then serves as calcium reservoir to participate in calcium metabolism.Liquid crystal and crystalline show dynamic changes in the development of chicken embryo,showing a unique mechanism of biomineralization and crystallization.I.Transport and absorption of calcium and other nutrients are very important during embryo development,which is the basis of calcium physiology in adults.The yolk sac of chicken embryo serves as calcium nutrients reservoir and provides energy for various tissues and organs during the development.Liquid crystal and crystal are the two main forms of nutrients in yolk sac.Studying the transport patterns and related pathways of liquid crystalline nutrients may provide valuable information for better understanding the development and maturation of embryonic organs.Our previous data showed that yolk sac jejunum/ileum mesenteric complex（YC-JI mesenteric complex）promoted the degeneration of yolk sac.In order to further explore the role of this complex in nutrient transfer,a series of liquid crystal activity tests were carried out on the mesenteric complex of chicken embryos.Our research data summarized as follows:（1）Mesentery,a newly defined organ in 2017,together with yolk sac,yolk duct,blood vessel,jejunum and ileum,forms a in chicken embryo.YC-JI mesenteric complex showed obvious birefringence optical lipid droplets under polarized light.These lipid droplets existed in form of islands,displayijng the unique phase transition and fluidity of liquid crystal.（2）This birefringence active substances were also detected near the capsule cavity of heart,lung and kidney.During embryo development,liquid crystals firstly appear in yolk sac.According to the time series of organ formation,we proposed that the nutrients in yolk sac,on the one hand,were directly transported to intestinal tract through yolk tube,on the other hand,they were transported to mesenteric space by attaching to vascular wall.The fluidity of liquid crystals enables them to be transported to various tissues and organs without damaging the structure and function of mesentery.Our data suggest that one of the potential new functions of mesentery is nutrient transport during embryonic development.II.Liquid crystal and crystalline is closely related to the homeostasis of sex hormone and calcium.Liquid crystal is literally found in embryo development stage,and rarely reported in normal adult.However,some studies have found that liquid crystal reappeared in adult organs when disease occured,such as cholesterol crystal reported in nonalcoholic fatty hepatitis.Studies have shown high similarity between liquid crystal in chicken embryo liver and yolk sac,and the occurrence of crystal and liquid crystal is closely related to liver physiological function.Based on this,we studied the liquid crystal substance in non-alcoholic fatty liver;Hormone cancer is closely related to homeostasis of hormone level in vivo.Based on the potential function of liquid crystal metabolites in maintaining sex hormone level,we have also investigated the liquid crystal in hormone prostate cancer.The results are summarized as follows:（1）The liver of nonalcoholic fatty liver mice presented pathological symptoms such as fatty degeneration and obvious optical birefringence structure under polarized light.The main components of these birefringent structures were cholesterol oleate,which showed typical phase trasition and fluidity of liquid crystal.The liver lipid drops in patient non-alcoholic fatty liver also showed birefringence optical activity,and the optical distribution was limited to the cortex of spherical lipid drops in early stage of disease.The degree of lipid saturation in hepatocytes maybe closely related to the production of liver lipid drops.（2）The tissue structure of nonalcoholic fatty liver,especially near blood vessels,displayed dispersion state compared with normal liver.Therefore,we studied the relationship between autophagy and lipid drop accumulation.The results showed that the expression of autophagy marker proteins MAP1LC3A and Beclin-1 were significantly decreased in non-alcoholic fatty liver,which suggested that autophaty was closely related to the lipid accumulation in hepatocytes.By exploring the liquid crystal characteristics of lipid drops in nonalcoholic fatty liver,we expect that the severity of symptoms can be revealed by detecting the birefringence of liver lipid drops in patients with nonalcoholic fatty liver,so as to provide a new way for monitoring and diagnosis of the disease.（3）Birefringent optical active substances were also detected in the pathological samples of hormone prostate cancer patients,which showed the lipid properties.In the highly differentiated prostate cancer samples,these birefringent substances presented as typical Maltese cross structures and crystal structures,while in the low differentiation prostate cancer samples,it was basically in liquid crystal structure.Therefore,we speculated that with the occurrence of prostate cancer,liquid crystal appearsed,and with the further development of cancer,the liquid crystal state gradually changed to crystal state,which have poorer plasticity and destruction,and this may be one of the reasons for serious damage of cell physiological function.Ⅲ.Calcium and hormone homeostasis are closely related to the appearance of crystalline and liquid crystal,and their mutual transition.The overload of calcium in organism will lead to the transformation of liquid crystal to the more destructive crystalline state,which will affect the physiological function of cells.Calcium usually performs its physiological functions together with calcium related protein.Previous data showed that crystal crystal was more likely to appear in the liver of calcium related NG37 transgene mice in high fat diet.In order to study the related molecular mechanism,we studied the function and phenotype of calcium related proteins in hormone cancer with high appearance of liquid crystal and crystalline.（1）The liquid crystal crystal in prostate cancer shows that its occurrence is closely related to calcium.It is reported that calcium may be an effective regulator of androgen receptor（AR）in prostate cancer cells.AR regulates its physiological activity through a variety of post-translational protein modifications,including phosphorylation and dephosphorylation.S81 phosphorylation is closely related to AR transcription activation and reactivation,and its dephosphorylation mainly occurs through calmodulin phosphatase PPTA and PP1.Our data showed that there were some different response proteins between AR-S81 phosphorylated and non-phosphorylated under hormonal stimulation,such as LDLR and HSPA1B;non-phosphorylated AR-S81 also presented transcriptional activation function;When compared with nonphosphorylated AR-S81,the histone acetyltransferase（HAT）p300,which is related to transcriptional activity,showed significantly higher affinity binding to phosphorylated AR-S81,while CBP,another HAT enzyme,did not show any difference;The inhibitor of calcium related protein PPTA promoted the interaction of AR and CBP,but inhibited the interaction of AR and p300.It is important to explore the selection of AR to p300 and CBP induced by PPTA inhibitors and the difference of physiological activities caused by this choice.（2）The coexistence of liquid crystal crystals in egg cells shows that calcium related proteins are closely related to ovarian disease.By studying the phenotype distribution of calcium related proteins and regulatory proteins in hormone ovarian cancer,we hope our data will provide new vision for screening new biomarkers of ovarian cancer.The results showed that,compared with the adjacent/normal tissues,the expression of calcium related protein IP3R3 and its regulators（CAMR2,PPTA B/C）was significantly up-regulated in tissues of ovarian tumors patients,and the expression of IP3R3 and CAMR2 was positively correlated with the degree of tumor differentiation,while the CAMR1 was negatively correlated.By analyzing the correlation between the mRNA expression level of calcium related genes and patient’s overall survival rate and disease-free survival rate in TCGA serous ovarian tumor database,the results showed that patients with up-regulated mRNA levels of ITPR3、CAMR1B、PPPTRIA、PPPTR2A and PPPTCA,or with down regulated CAMR1A mRNA level,which encoding IP3R3 and its regulators（CAMR 1/2,PPTA）seperately,had worse overall survival and disease-free survival,IP3R3,CAMR1/2 and PPTA maybe used as biomarkers for screening,diagnosing and prognosis of ovarian tumors.Taken together,the accumulation and transportation of calcium during embryonic development is an important basis of calcium physiology in adults.Liquid crystal substances in organisms are closely related to calcium and lipid accumulation.Studying the specific molecular mechanism and the related signaling pathways of liquid crystal substances appearance will help us better understand the development process of embryonic organs and the occurrence of diseases.The physiological function of calcium is inseparable with calcium related proteins.Studying the expression pattern and molecular mechanism of the calcium related proteins in embryonic development and disease occurrence may provide valuable information for high incidence of diseases in embryo and adult. |
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