ABSTRACT
@#Self-assembly is the basis of the formation of biological macromolecular structure. Enzyme-instructed self-assembly (EISA) with the help of tool enzymes, realizing the conversion of small molecular compounds to supramolecular nanostructures at specific sites, become a new strategy for drug discovery.In recent years, the exploration of EISA for developing malignant cancer therapy and imaging has made considerable progress, achieving the precise regulation and tumor targeting of nanostructures. This paper reviews the latest progress of EISA in the field of tumor diagnosis and treatment, the functions and characteristics of tool enzymes such as alkaline phosphatase, sirtuin, tyrosinase, γ-glutamyltranspeptidase and caspase-3,summarizes the research status of EISA targeting multiple organelles in tumor therapy, and introduces the application of EISA in tumor imaging, aiming to provide reference forthe research of EISA strategy in tumor diagnosis and treatment.
ABSTRACT
ABSTRACT Introduction: Improved long-term patency of the no-touch (NT) saphenous vein graft has been reported to result from the preservation of a healthy vascular microstructure, especially endothelial cells. However, the precise morphology of endothelial cells and their organelles in NT saphenous vein graft has not been fully investigated. In this study, we assessed the ultrastructure of preserved endothelial cells in saphenous vein graft using transmission electron microscopy. Methods: Intact control (IC) vein, NT saphenous vein graft, and conventional (CT) saphenous vein graft were harvested from a patient. After observation by light microscopy, the nuclei and mitochondria in the preserved endothelial cells were compared among IC, NT, and CT using transmission electron microscopy, and the endothelial organelles were assessed quantitatively. Results: Light microscopy showed that the preservation of endothelial cells was comparable in IC, NT, and CT. Subsequent transmission electron microscopy observation showed that the nuclei in preserved endothelial cells appeared more swollen in CT than that in NT. Quantitative analysis revealed that nuclear size and circularity of preserved endothelial cells in NT and IC were similar, but those in CT were larger and higher, respectively, than those in IC and NT. In addition, the mitochondrial size in preserved endothelial cells in CT was larger than that in IC and NT. Conclusion: Necrotic changes in endothelial organelles characterized by swelling of nuclei and mitochondria were prominent in CT saphenous vein graft. The normally maintained ultrastructure of preserved endothelial cells in NT saphenous vein graft could contribute to long-term patency.
ABSTRACT
During mitosis, the allocation of genetic material concurs with organelle transformation and distribution. The coordination of genetic material inheritance with organelle dynamics directs accurate mitotic progression, cell fate determination, and organismal homeostasis. Small GTPases belonging to the Ras superfamily regulate various cell organelles during division. Being the key regulators of membrane dynamics, the dysregulation of small GTPases is widely associated with cell organelle disruption in neoplastic and non-neoplastic diseases, such as cancer and Alzheimer's disease. Recent discoveries shed light on the molecular properties of small GTPases as sophisticated modulators of a remarkably complex and perfect adaptors for rapid structure reformation. This review collects current knowledge on small GTPases in the regulation of cell organelles during mitosis and highlights the mediator role of small GTPase in transducing cell cycle signaling to organelle dynamics during mitosis.
Subject(s)
Humans , Mitosis , Monomeric GTP-Binding Proteins , Neoplasms , Organelles/physiology , Signal TransductionABSTRACT
In recent years, the use of the body's immune system for anti-tumor immunotherapy has received extensive attention. However, the immunosuppressive tumor microenvironment (TME) limits the effect of immunotherapy. Therefore, overcoming the limitations of TME and immunosuppressive cells plays an important role in tumor immunotherapy. Nano agents have great potential to reprogram the immunosuppressive microenvironment and provide an effective strategy for immunotherapy. With the continuous development of active targeting nano carrier technology and the deepening of the research on drug action sites, subcellular organ targeting nano carrier materials with more accurate active targeting function have also attracted more and more attention. This review will briefly introduce the relationship between subcellular organelles and tumor, summarize the design strategy and research progress of targeted nano drug delivery system based on the characteristics of acidity, reactive oxygen species (ROS) activity, immunogenicity, and TME of immunosuppressive cells, to provide reference for the construction of subcellular pathway targeted drug delivery system in tumor immunotherapy.
ABSTRACT
Fixation is one of the processes in preparing histology and pathology. The common material for fixation is buffered formalin including paraformaldehyde. However, the effect of the damaged cells, which is fixed for a long time, causes the research for other fixation materials to become necessary. In addition, paraformaldehyde is also harmful to human body and natural environment. Ethanol is one of the alternative fixation materials, which has been used for two hundred years. It has been used for many purposes, both in routine staining and immunohistochemistry. Nonetheless, no research confirms its effect on the electron microscope. The authors studied the effect of 50 % of ethanol on the cell membrane, organelles, and nucleus of Purkinje cells (Neuron purkinjense) observed on a light microscope and Transmitted Electron Microscope (TEM). Then it was compared to buffered formalin. In the light microscope, it shows that both of fixations have no different effects of the morphology of the cell membrane, cytoplasm, the nucleus of Purkinje cells and the neutrophils. We assume that our 50 % of ethanol concentration is almost the same as BF 10 % in the ability of hardening tissue and color absorption based on the previous study. In TEM, the structure of the cell membrane, organelles, and cytoplasm of Purkinje cell look broken in the cerebellum of 50 % of ethanol except for the nucleus. There was no significant difference diameter of the nucleus. It happened in general because of the shrinkage effect of ethanol. However, the authors recommend using 50 % of ethanol for routine staining.
La fijación es uno de los procesos en la preparación de muestras para histología y patología. El material más común para la fijación es la formalina tamponada. Sin embargo, el daño a las células que se mantienen en formalina durante mucho tiempo, hace necesario buscar otros materiales de fijación. Además, el paraformaldehido también es perjudicial para el cuerpo humano y el medio ambiente natural. El etanol es uno de los materiales de fijación alternativos que se ha utilizado durante muchos años, con diversos objetivos, tanto en la tinción de rutina como en la inmunohistoquímica. Sin embargo no se ha confirmdo su efecto con microscopio electrónico. Los autores estudiaron el efecto del 50 % de etanol sobre la membrana celular, los orgánulos y el núcleo de las células de Purkinje observados en un microscopio óptico y un microscopio de transmisión electrónico (TEM). Luego se comparó con la formalina tamponada. En el microscopio óptico se observó que ambas fijaciones no tienen efectos diferentes a la morfología de la membrana celular, el citoplasma, el núcleo de las células de Purkinje y los neutrófilos. Suponemos que nuestra concentración de 50 % de etanol es casi la misma que BF 10 % en la capacidad de endurecer el tejido y la absorción de color según el estudio anterior. En TEM, la estructura de la membrana celular, los orgánulos y el citoplasma de la célula de Purkinje presentaban daño en el cerebelo con un 50 % de etanol, a excepción del núcleo. No hubo diferencia significativa en el diámetro del núcleo. En general lo anterior se debió al efecto de contracción del etanol. En conclusión los autores recomiendan usar 50% de etanol para la tinción de rutina.
Subject(s)
Animals , Male , Mice , Brain/drug effects , Brain/ultrastructure , Tissue Fixation/methods , Ethanol/pharmacology , Microscopy, Electron , Organelles/drug effects , Organelles/ultrastructure , Mice, Inbred BALB CABSTRACT
Camellia oil has become an important plant oil in China in recent years, but its effects on non-alcoholic fatty liver disease (NAFLD) have not been documented. In this study, the effects of camellia oil, soybean oil, and olive oil on NAFLD were evaluated by analyzing the fatty acid profiles of the plant oils, the serum lipids and lipoproteins of rats fed different oils, and by cytological and ultrastructural observation of the rats’ hepatocytes. Analysis of fatty acid profiles showed that the polyunsaturated fatty acid (PUFA) n-6/n-3 ratio was 33.33 in camellia oil, 12.50 in olive oil, and 7.69 in soybean oil. Analyses of serum lipids and lipoproteins of rats showed that the levels of total cholesterol and low-density lipoprotein cholesterol in a camellia oil-fed group (COFG) were lower than those in an olive oil-fed group (OOFG) and higher than those in a soybean oil-fed group (SOFG). However, only the difference in total cholesterol between the COFG and SOFG was statistically significant. Cytological observation showed that the degree of lipid droplet (LD) accumulation in the hepatocytes in the COFG was lower than that in the OOFG, but higher than that in the SOFG. Ultrastructural analysis revealed that the size and number of the LDs in the hepatocytes of rats fed each of the three types of oil were related to the degree of damage to organelles, including the positions of nuclei and the integrity of mitochondria and endoplasmic reticulum. The results revealed that the effect of camellia oil on NAFLD in rats was greater than that of soybean oil, but less than that of olive oil. Although the overall trend was that among the three oil diets, those with a lower n-6/n-3 ratio were associated with a lower risk of NAFLD, and the effect of camellia oil on NAFLD was not entirely related to the n-6/n-3 ratio and may have involved other factors. This provides new insights into the effect of oil diets on NAFLD.
ABSTRACT
@#Organelles have their special functions, they interact with each other and coordinate a series of important physiological functions at the same time. Organelle interaction occurs at membrane contact sites(MCSs), where the membranous organelle endoplasmic reticulum is the core, and specific tethered proteins at the membrane contact site bind to the organelle membrane and various protein complexes work together to perform specific functions, such as lipid transport, Ca2+ transfer, etc. This review studies on the structure and function of membrane contact sites and their key roles in organelle interactions, focusing on the connection between the endoplasmic reticulum and plasma membrane, mitochondria and Golgi, as well as the association between the key proteins at membrane contact sites and the occurrence and development of various diseases.
ABSTRACT
Objective To investigate the effects of high intensity electric field on cell growth,apoptosis and microstructure of human pancreatic cancer cell line PANC-1.Methods The PANC-1 cells in the logarithmic growth period were selected,and cells in the high voltage electrical treatment group were treated with high voltage electric field 250,500,750,1000 V/cm,respectively.The effects of different high voltage electric fields on cell growth and microstructure of PANC-1 cells were determined by cell viability,cell death staining,apoptosis detection,transmission electron microscopy and scanning electron microscopy.Results Compared with control group,the high voltage electric pulse significantly inhibited the growth of PANC-1 cells in the field dependent manner.Moreover,when the field was more than 500 V/cm,the cell viability was significantly decreased (P＜0.05).High voltage electric pulse could induce cell apoptosis.When the field was higher than 750 V/cm,serious necrosis was noticed.In the 1000 V/cm group,the integrity of cell membrane and the structure of organelles was seriously damaged.Conclusion High voltage electric pulse could significantly inhibit the growth of PANC-1 cells and would be a promising method in cancer treatment.
ABSTRACT
Cells utilize calcium ions (Ca) to signal almost all aspects of cellular life, ranging from cell proliferation to cell death, in a spatially and temporally regulated manner. A key aspect of this regulation is the compartmentalization of Ca in various cytoplasmic organelles that act as intracellular Ca stores. Whereas Ca release from the large-volume Ca stores, such as the endoplasmic reticulum (ER) and Golgi apparatus, are preferred for signal transduction, Ca release from the small-volume individual vesicular stores that are dispersed throughout the cell, such as lysosomes, may be more useful in local regulation, such as membrane fusion and individualized vesicular movements. Conceivably, these two types of Ca stores may be established, maintained or refilled via distinct mechanisms. ER stores are refilled through sustained Ca influx at ER-plasma membrane (PM) membrane contact sites (MCSs). In this review, we discuss the release and refilling mechanisms of intracellular small vesicular Ca stores, with a special focus on lysosomes. Recent imaging studies of Ca release and organelle MCSs suggest that Ca exchange may occur between two types of stores, such that the small stores acquire Ca from the large stores via ER-vesicle MCSs. Hence vesicular stores like lysosomes may be viewed as secondary Ca stores in the cell.
ABSTRACT
Mitochondria is an important organelle in mammalian cells with multiple functions,such as ener-gy production and cell homeostasis maintaining. It is known that hundreds of diseases are associated with mi-tochondrial defects. The studies show that the exoge-nous mitochondria can directly enter mammalian cells in vitro, and they also can quickly transform into ani-mal tissues by local or intravenous injection. Current-ly, it has raised a new therapeutic strategy for mito-chondrial diseases, called mitotherapy, which trans-plants exogenous functional mitochondria into mito-chondria-defective cells. The mitochondria in recipient cells play their own roles, including energy produc-tion,maintaining free radical balance,and cell viabili-ty recovery. Since there is no effective method for mito-chondria-related diseases up to now, the mitotherapy will provide a new approach for the prevention and treatment of these diseases.
ABSTRACT
The lipid droplet (LD) is a unique multi-functional organelle that contains a neutral lipid core covered with a phospholipid monolayer membrane. The LDs have been found in almost all organisms from bacteria to humans with similar shape. Several conserved functions of LDs have been revealed by recent studies, including lipid metabolism and trafficking, as well as nucleic acid binding and protection. We summarized these findings and proposed a hypothesis that the LD is a conserved organelle.
Subject(s)
Animals , Humans , Bacteria , Metabolism , Biological Evolution , Cholesterol Esters , Metabolism , Lipid Droplets , Chemistry , Metabolism , Lipid Metabolism , Genetics , Nucleic Acids , Metabolism , Peptide Initiation Factors , Chemistry , Metabolism , Protein Binding , RNA-Binding Proteins , Chemistry , Metabolism , Ribosome Subunits , Chemistry , Metabolism , Triglycerides , MetabolismABSTRACT
The endoplasmic reticulum (ER) plays a crucial role in various cellular activities and cell survival. Almost all of the resident proteins usually enter the ER, and are modified with N-linked glycans and folded into the appropriate secondary and tertiary structures. When cells are faced with stressful conditions, unfolded proteins are accumulated in the ER. The discrepancies between the protein folding capacities and client protein load lead to ER stress. If the stress is prolonged, ER stress responses can activate apoptosis. ER stress-mediated apoptosis is implicated in the pathophysiology of human diseases, including several neurodegenerative diseases, diabetes mellitus, and various infectious diseases. Thus, the ER is now considered as an important organelle that can decide cell survival or death. In this review, the recent progress on ER stress and apoptosis is summarized.
Subject(s)
Humans , Apoptosis , Cell Survival , Communicable Diseases , Diabetes Mellitus , Endoplasmic Reticulum , Endoplasmic Reticulum Stress , Neurodegenerative Diseases , Organelles , Polysaccharides , Protein Folding , ProteinsABSTRACT
The changes of cell ultra structure as well as Ca2+ homeostasis involved in the drought-induced maize leaf senescence was investigated. Meanwhile, many indicatives of leaf senescence including thiobarbituric acid reactive substance (MDA), electrolyte leakage (EL), and chlorophyll along with soluble proteins were also detected during the process. The Polyethylene glycol6000(PEG6000)-incubated detached leaves showed a slight increase in the MDA content and electrolyte leakage during the first 30 min of our detection, which was corresponded to an unobvious alteration of the cell ultrastructure. Other typical senescence parameters measured in whole leaf exhibited a moderate elevation as well. Thereafter, however, the EL and MDA rose to a large extent, which was correlated with a dramatic damage to the cell ultrastructure with concomitant sharp decrease in the chlorophyll and soluble proteins content. The deposits of calcium antimonite, being an indicator for Ca2+ localization, were observed in the vacuoles as well as intercellular spaces in the leaves grown under normal condition. Nevertheless, after PEG treatment, it was revealed a distinct increment of Ca2+ in the cytoplasm as well as chloroplasts and nuclei. Moreover, with long-lasting treatment of PEG to the detached leaves, the concentration of Ca2+ as described above showed a continuous increment which was consist with the remarked alteration of physiological parameters and severe damage to the ultrastructure of cells, all of which indicated the leaf senescence. Such drought-induced leaf senescence might result from a loss of the cell's capability to extrude Ca2+. All above findings give us a good insight into the important role of Ca2+ homeostasis in the process of leaf senescence accelerated by the drought stress.
Subject(s)
Calcium , Cellular Senescence , Droughts , Plant Leaves , Zea mays , Chlorophyll/analysis , Electrolytes , Homeostasis , Lipid Peroxidation , Mesophyll Cells , Stress, Physiological , Signal TransductionABSTRACT
@#ObjectiveTo detect the ultrastructure of neural stem cells (NSCs) cultured in vitro .MethodsNSCs separated from the cortex of 17—19 days Wistar rat fetus were cultured and induced to differentiate in vitro. Electron microscopes were used to visualize the ultrastructure of these cells before and after differentiation.ResultsNSCs had the similar cellular size, morphology and intracellular structures pre-differentiation. Cells were able to proliferate via mitosis. The nucleus/cytoplasm ratio was very high. The nucleus was poly-morphological. Cells had very little cytoplasm and no mature organelles. After differentiation, several processes protruded out from cellular surface. Cells became flat shape, the volume of cytoplasm increased dramatically and various kinds of mature organelles appeared in the cytoplasm. Cells differentiated into two kinds of cells,neural cells and glial cells,with quite different morphology and intracellular structure. ConclusionNSC is one kind of original cells which can be induced to differentiate into mature neural cells and glial cells.
ABSTRACT
Fractionation of methanolic extracts of air dried aerial parts of Parthenium resulted in the isolation of a toxic constituent which was identified as parthenin, the major sesquiterpene lactone from the weed. The LD50 (minimal lethal dose required to cause 50% mortality) for parthenin in rats was 42 mg/kg body weight. When [3H]-parthenin was given orally or by intravenous administration, radioactivity appeared in the milk of lactating laboratory and dairy animals. Tissue distribution of radioactivity revealed that maximum label was detectable in kidneys.
ABSTRACT
Objective To study the mechanism of myocardical aging. Methods Wistar rats used were divided aging group (22 months old) and adult group (7 months old). Qualitative morphological changes of organelles of myocardium were observed by TEM. Quantitative morphological changes of organelles of myocardium were determined by stereological method, Ca 2+ regulation of organelles of myocardium were analysed by EDS. Results Compared with adult group, aging group:(1) The nuclei were indented, myofibril were arranged irregularly, intercalated disk were separated, mitochondria and sarcoplasmic reticulum were swelled, lipofuscin and residual body were increased. (2) The volume of myocardium not occupied by myocyte were increased, the volume density of mitochondria and sarcoplasmic reticulum were reduced, specific surface of outer membrance of mitochondria inter membrane plus cristae of mitochondria and the membrane of sarcoplasmic reticulum were also reduced. (3) Ca 2+ in myofibril and mitochondria were increased, but Ca 2+ in sarcoplasmic reticulum were decreased. Conclusion The contractility of aging myocardium were declined, the morphological changes and Ca 2+ regulation of mitochondria and sarcoplasmic reticulum might be directly related to myocardical aging.