AIM To investigate the application of confocallaser scanning microscopy(CLSM)in tumorpathology and three-dimensional( 3-D )reconstruction by CLSM in pathologic specimensof hepatocellular carcinoma(HCC).METHODS The 30...AIM To investigate the application of confocallaser scanning microscopy(CLSM)in tumorpathology and three-dimensional( 3-D )reconstruction by CLSM in pathologic specimensof hepatocellular carcinoma(HCC).METHODS The 30μm thick sections were cutfrom the paraffin-embedded tissues of HCC,hyperplasia and normal liver,stained with DNAfluorescent probe YOYO-1 iodide and examinedby CLSM to collect optical sections of nuclei and3-D images reconstructed.RESULTS HCC displayed chaotic arrangementof carcinoma cell nuclei,marked pleomorphism,indented and irregular nuclear surface,andirregular and coarse chromatin texture.CONCLUSION The serial optical tomograms ofCLSM can be used to create 3-D reconstruction ofcancer cell nuclei.Such 3-D impressions mightbe helpful or even essential in making anaccurate diagnosis.展开更多
Energy metabolism is a fundamental biological process that is vital for the survival of all species. Disorders in the metabolic system result in deficiency or redundancy of certain nutrients, including carbohydrates, ...Energy metabolism is a fundamental biological process that is vital for the survival of all species. Disorders in the metabolic system result in deficiency or redundancy of certain nutrients, including carbohydrates, lipids, amino acids, etc. Abnormality of the energy metabolism system leads to a number of metabolic diseases, such as the metabolic syndrome. Broadly speaking, the term "metabolic diseases" now tends to be widened to the category that refers to all diseases with metabolism disorder. It is shown that many diseases associate with metabolic disorders. For example, most malignant tumors progress with mal-nutrition and high consumption, that is, cachexia. Many components of the energy metabolism system, such as lactate dehydrogenase (LDH), are now widely applied in clinical examinalions as special markers for tumors and some other diseases. Opioid dependence and addiction are neurobiological diseases associated with malregulation of the metabolic system. However, how chronic drug administration induces metabolic abnormality is not understood. In a recent issue of Cell Research, research group of Jing-Gen Liu reports an interesting discovery that three metabolic enzymes are changed in mice after chronic morphine treatment, suggesting new roles of metabolic enzymes as a potential link that associates metabolic disorder with opioid dependence.展开更多
Fyn kinase-dependent cellular events were related with skeletal muscle denervation. In the present study, we used a combination of techniques to measure ER stability and the related Gβ1γ2 trafficking following muscl...Fyn kinase-dependent cellular events were related with skeletal muscle denervation. In the present study, we used a combination of techniques to measure ER stability and the related Gβ1γ2 trafficking following muscle mobilization, and demonstrated a temporally and Fyn-dependent up-regulation of Ca2+ level in the mobilized muscle. In parallel, Fyn activity in ER was gradually decreased, which was accompanied by enhanced PTP1B activity and expressions of ER proteins (calnexin, Grp94, cyclophilin, and Hsp70). Moreover, during muscle mobilization, there was more membrane protein breakdown than protein synthesis, which probably featured robust Gβ1γ2 internalization, and Rab1-dependent transport into ER compartment;the signaling was related to disruption of PI3K-Akt signaling and decrement of muscular functions. Then, Gβ1γ2 trafficking is a key component necessary for the early recovery processes regarding muscle atrophy, which would be the therapeutic consideration for muscle repair and regeneration.展开更多
During the past decade, significant advances have been made in refinements for regenerative therapies following human spinal cord injury (SCI). Positive results have been achieved with different types of cells in va...During the past decade, significant advances have been made in refinements for regenerative therapies following human spinal cord injury (SCI). Positive results have been achieved with different types of cells in various clinical studies of SCI. In this review, we summarize recently-completed clinical trials using cell- mediated regenerative therapies for human SCI, together with ongoing trials using neural stem cells. Specifically, clinical studies published in Chinese journals are included. These studies show that current transplantation therapies are relatively safe, and have provided varying degrees of neurological recovery. However, many obstacles exist, hindering the introduction of a specific clinical therapy, including complications and their causes, selection of the target population, and optimization of transplantation material. Despite these and other challenges, with the collaboration of research groups and strong support from various organizations, cell-mediated regenerative therapies will open new perspectives for SCI treatment.展开更多
Background Since an effective method for generating induced pluripotent stem cells (iPSCs) from human neural stem cells (hNSCs) can offer us a promising tool for studying brain diseases, here we reported direct re...Background Since an effective method for generating induced pluripotent stem cells (iPSCs) from human neural stem cells (hNSCs) can offer us a promising tool for studying brain diseases, here we reported direct reprogramming of adult hNSCs into iPSCs by retroviral transduction of four defined factors. Methods NSCs were successfully isolated and cultured from the hippocampus tissue of epilepsy patients. When combined with four factors (OCT3/4, SOX2, KLF4, and c-MYC), iPSCs colonies were successfully obtained. Results Morphological characterization and specific genetic expression confirmed that these hNSCs-derived iPSCs showed embryonic stem cells-like properties, which include the ability to differentiate into all three germ layers both in vitro and in vivo. Conclusion Our method would be useful for generating human iPSCs from NSCs and provide an important tool for studying neurological diseases.展开更多
Memory by Engineered Mutagenesis with Optical In situ Readout(MEMOIR)is a novel strategy for lineage tracing that combines Cas9/g RNA and sequential multiplexed single-molecule RNA fluorescence hybridization(seqFIS...Memory by Engineered Mutagenesis with Optical In situ Readout(MEMOIR)is a novel strategy for lineage tracing that combines Cas9/g RNA and sequential multiplexed single-molecule RNA fluorescence hybridization(seqFISH)[1],which was created by Cai Long et al.at the California Institute of Technology[2].In MEMOIR,dynamic cellular event histories are recorded,then read out in single cells using seq FISH.Here,we introduce the展开更多
文摘AIM To investigate the application of confocallaser scanning microscopy(CLSM)in tumorpathology and three-dimensional( 3-D )reconstruction by CLSM in pathologic specimensof hepatocellular carcinoma(HCC).METHODS The 30μm thick sections were cutfrom the paraffin-embedded tissues of HCC,hyperplasia and normal liver,stained with DNAfluorescent probe YOYO-1 iodide and examinedby CLSM to collect optical sections of nuclei and3-D images reconstructed.RESULTS HCC displayed chaotic arrangementof carcinoma cell nuclei,marked pleomorphism,indented and irregular nuclear surface,andirregular and coarse chromatin texture.CONCLUSION The serial optical tomograms ofCLSM can be used to create 3-D reconstruction ofcancer cell nuclei.Such 3-D impressions mightbe helpful or even essential in making anaccurate diagnosis.
文摘Energy metabolism is a fundamental biological process that is vital for the survival of all species. Disorders in the metabolic system result in deficiency or redundancy of certain nutrients, including carbohydrates, lipids, amino acids, etc. Abnormality of the energy metabolism system leads to a number of metabolic diseases, such as the metabolic syndrome. Broadly speaking, the term "metabolic diseases" now tends to be widened to the category that refers to all diseases with metabolism disorder. It is shown that many diseases associate with metabolic disorders. For example, most malignant tumors progress with mal-nutrition and high consumption, that is, cachexia. Many components of the energy metabolism system, such as lactate dehydrogenase (LDH), are now widely applied in clinical examinalions as special markers for tumors and some other diseases. Opioid dependence and addiction are neurobiological diseases associated with malregulation of the metabolic system. However, how chronic drug administration induces metabolic abnormality is not understood. In a recent issue of Cell Research, research group of Jing-Gen Liu reports an interesting discovery that three metabolic enzymes are changed in mice after chronic morphine treatment, suggesting new roles of metabolic enzymes as a potential link that associates metabolic disorder with opioid dependence.
文摘Fyn kinase-dependent cellular events were related with skeletal muscle denervation. In the present study, we used a combination of techniques to measure ER stability and the related Gβ1γ2 trafficking following muscle mobilization, and demonstrated a temporally and Fyn-dependent up-regulation of Ca2+ level in the mobilized muscle. In parallel, Fyn activity in ER was gradually decreased, which was accompanied by enhanced PTP1B activity and expressions of ER proteins (calnexin, Grp94, cyclophilin, and Hsp70). Moreover, during muscle mobilization, there was more membrane protein breakdown than protein synthesis, which probably featured robust Gβ1γ2 internalization, and Rab1-dependent transport into ER compartment;the signaling was related to disruption of PI3K-Akt signaling and decrement of muscular functions. Then, Gβ1γ2 trafficking is a key component necessary for the early recovery processes regarding muscle atrophy, which would be the therapeutic consideration for muscle repair and regeneration.
基金supported by grants from the National Natural Science Foundation of China (81271003)he National Basic Research Development Program (973 Program) of China (2010CB945500,2012CB966300,2009CB941100)
文摘During the past decade, significant advances have been made in refinements for regenerative therapies following human spinal cord injury (SCI). Positive results have been achieved with different types of cells in various clinical studies of SCI. In this review, we summarize recently-completed clinical trials using cell- mediated regenerative therapies for human SCI, together with ongoing trials using neural stem cells. Specifically, clinical studies published in Chinese journals are included. These studies show that current transplantation therapies are relatively safe, and have provided varying degrees of neurological recovery. However, many obstacles exist, hindering the introduction of a specific clinical therapy, including complications and their causes, selection of the target population, and optimization of transplantation material. Despite these and other challenges, with the collaboration of research groups and strong support from various organizations, cell-mediated regenerative therapies will open new perspectives for SCI treatment.
基金This work was supported by grants from the Major State Basic Research Program (No. 2010CB945500, No. 2012CB966300, and No. 2009CB941100), the National Natural Science Foundation of China (No. 81271003 and No. 81200936), Shanghai Committee of Science and Technology (No. 08dj140053), and 2011 Shanghai Medical College Young Scientist Fund of Fudan University (11L-24).Acknowledgements: We are grateful to technicians CHEN Lu-ping, SHEN Yi-wen and TANG Qi-sheng in our lab for their kind assistance in animal preparation and cell culture. We also thank Dr. SHA Hong-ying for picture processing and helpful comments and suggestions.
文摘Background Since an effective method for generating induced pluripotent stem cells (iPSCs) from human neural stem cells (hNSCs) can offer us a promising tool for studying brain diseases, here we reported direct reprogramming of adult hNSCs into iPSCs by retroviral transduction of four defined factors. Methods NSCs were successfully isolated and cultured from the hippocampus tissue of epilepsy patients. When combined with four factors (OCT3/4, SOX2, KLF4, and c-MYC), iPSCs colonies were successfully obtained. Results Morphological characterization and specific genetic expression confirmed that these hNSCs-derived iPSCs showed embryonic stem cells-like properties, which include the ability to differentiate into all three germ layers both in vitro and in vivo. Conclusion Our method would be useful for generating human iPSCs from NSCs and provide an important tool for studying neurological diseases.
基金supported by the grants from the National Natural Science Foundation of China (81271003)the Ministry of Science and Technology of China (2013CB967400, 2012CB966300, and ZJ2014-ZD-002)
文摘Memory by Engineered Mutagenesis with Optical In situ Readout(MEMOIR)is a novel strategy for lineage tracing that combines Cas9/g RNA and sequential multiplexed single-molecule RNA fluorescence hybridization(seqFISH)[1],which was created by Cai Long et al.at the California Institute of Technology[2].In MEMOIR,dynamic cellular event histories are recorded,then read out in single cells using seq FISH.Here,we introduce the