Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focus...Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focused on the production and pharmacological side effects caused by H_(2)S.Therefore,effective strategies to remove H_(2)S has become a key research topic.Furthermore,the development of novel nanoplatforms has provided new tools for the targeted removal of H_(2)S.This paper was performed to review the association between H_(2)S anddisease,relatedH_(2)S inhibitory drugs,aswell as H_(2)S responsive nanoplatforms(HRNs).This review first analyzed the role of H_(2)S in multiple tissues and conditions.Second,common drugs used to eliminate H_(2)S,as well as their potential for combination with anticancer agents,were summarized.Not only the existing studies on HRNs,but also the inhibition H_(2)S combined with different therapeutic methods were both sorted out in this review.Furthermore,this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail.Finally,potential challenges of HRNs were proposed.This study demonstrates the excellent potential of HRNs for biomedical applications.展开更多
Aqueous and hydro-alcoholic extracts of Achillea fragrantissima L. (Asteraceae) grown in Jordan were screened for their antioxidant, antimicrobial, antiplatelet, anti-proliferative and acetylcholinesterase (AChE) inhi...Aqueous and hydro-alcoholic extracts of Achillea fragrantissima L. (Asteraceae) grown in Jordan were screened for their antioxidant, antimicrobial, antiplatelet, anti-proliferative and acetylcholinesterase (AChE) inhibition efficacy. Total phenols and flavonoids were determined colorimetrically. The radical scavenging activities were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical scavenging activity assays. High performance liquid chromatography-mass spectrometry (HPLCMS) analysis resulted in the identification of 7 phenolic compounds in the hydro-alcoholic extract and 4 compounds in the aqueous extract;quercetin 3-β-D-glucoside was the main component for both extracts. Antimicrobial activities were determined by antimicrobial susceptibility testing such as agar well-diffusion method, minimum inhibition concentration and minimum bactericidal concentration. Gram positive bacteria showed sensitivity to hydro-alcoholic extract in the agar-well diffusion test. No significant activity was observed against gram negative bacteria and Candida albicans. Hydro-alcoholic extract had a bactericidal activity against Streptococcus pneumoniae and Bacillus cereus at high concentrations (MIC 12.5 mg/ml) rather than inhibitory effect. In vitro antiplatelet activity was tested on human whole blood using an electrical impedance method. At concentrations (50, 100, and 200 μg/ml), no effect on platelet aggregation was noticed. Anti-proliferative activity was investigated using the MTT assay. At concentrations up to 200 μg/ml, extracts did not possess cytotoxic activity against the MCF-7 cells. Acetylcholinesterase (AChE) inhibitory capacity of A. fragrantissima extracts was tested using TLC assay method, and neither aqueous, nor hydroalcoholic extracts showed AChE inhibition. The present investigation supported the traditional use of A. fragrantissima in the Jordanian folk medicine as an antimicrobial active representative of the genus Achillea. A. fragrantissima extracts should be further studied for their potential use in preventing/treating diseases in which oxidative stress is a part of the pathophysiology.展开更多
Traditional Chinese medicine (TCM) is deeply rooted in ancient Chinese culture and has been practiced by Chinese people for thousands of years in order to maintain their health and fight against disease. This ancient ...Traditional Chinese medicine (TCM) is deeply rooted in ancient Chinese culture and has been practiced by Chinese people for thousands of years in order to maintain their health and fight against disease. This ancient Chinese wisdom has accumulated from the long struggle to cope with various diseases through hundreds or even thousands of trial-and-error practices. However, due to its empirical character, TCM has long been criticized as being deficient in scientific evidence, and is still not widely accepted by the mainstream conventional medical system. The complexity of the chemical components of TCM and the clarification of its mechanisms remain an enormous challenge in the conversion of TCM into an evidence-based medicine. Thanks to incredible progress in biomedical research, TCM has evolved at an astonishing pace in various aspects, as indicated by the 2015 Nobel Prize awarded to Professor Youyou Tu for her discovery of artemisinin.展开更多
Recent progress in bioinorganic chemistry studies of rare earth elements (REE) in animal cells was outlined, and the definition of REE′s biological intelligence as well as their mechanism were also explained. The mig...Recent progress in bioinorganic chemistry studies of rare earth elements (REE) in animal cells was outlined, and the definition of REE′s biological intelligence as well as their mechanism were also explained. The migration of REE from weathering rocks to the environment is accelerated by various anthropogenic activities, which can eventually result in the entrance of REE into animal and human bodies via food chain. REE can be found in body tissues such as brain, blood, muscle as well as bone. Based on their geochemical properties, REE in low dose show their unique biological intelligence by intervening in the process of signal transduction and its regulation, arteriosclerosis and blood clotting prevention, anticancer, and the promotion of cellular defense enzymes′ activities, nucleic acid metabolism enzymes as well as ATPases, etc. The meaning of REE′s biological intelligence refers to physicochemical properties-based capability to choose the targets (e.g., biometals) in biomolecules for the chelation or replacement of REE, and change the structures and functions of biomolecules, and consequently impact or control the biological functions or behaviors in living organisms. The regulation of various cellular processes caused by REE is mainly via antagonism or replacement of essential target biometals like calcium or via chelation of organic molecules, thereby embodying the unparalleled biological intelligence of REE. Additionally, the dosage effect of REE was also discussed from the angles of yin-yang dichotomy, bioavailability, entropy and evolution. In order to make full use of REE′s biological intelligence in the application for medicine, more detailed studies concerning dosage effect of REE and REE bioaccumulation in organisms should be conducted in future research.展开更多
BACKGROUND： Choosing proper donor cells is one of keys in experimental and clinical studies on cell replacement therapy （CRT） for treating Parkinson disease （PD）. Embryonic mesencephalic precursor cells （MPCs） ...BACKGROUND： Choosing proper donor cells is one of keys in experimental and clinical studies on cell replacement therapy （CRT） for treating Parkinson disease （PD）. Embryonic mesencephalic precursor cells （MPCs） can stably differentiate into dopaminergic neuron after in vitro proliferated culture. As compared with embryonic stem cell and neural stem cell strains, cell composition of embryonic MPCs after primary culture is also the most close to that of embryonic mesencephalic ventral cell suspension without proliferated culture. Successful experience accumulated in the latter suggests that primary cultured embryonic MPCs might be the most potential donor cells in clinical application with CRT for treating PD so far. OBJECTIVE： To investigate the feasibility of primary cultured embryonic precursor cells cultured primarily as donor cells in CRT for treating PD in rats. DESIGN ： A randomized and controlled trial taking SD rats as experimental animals.SETTING： Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University.MATERIALS： This experiment was carried out at the Institute of Neuroscience, Shanghai Institute for Biological Science, Chinese Academy of Sciences from July 2003 to June 2004. Totally 26 female SD rats, with body mass of 200 to 220 g, were provided by Shanghai Experimental Animal Center of Chinese Academy of Sciences. METHODS ： Stereotaxic injection of 6-hydroxydopamine into the medial forebrain bundle were perfored to develop PD model rat. Among 26 SD rats, 20 rats achieved a more than 5 turns/min in apomorphine induced rotation test, reaching the standard of PD model rats. Immunohistochemical detection was performed on 1 out of 20 model rats after execution, and the other 19 rats were randomly divided into control group （n=5）, sham transplantation group （n=5）and cell grafted group （n=9）. Primary cultured E12 MPC cell suspension （1.2×10^11 L^-1）were used as donor cells. 4μL primary cultured E12 MPC cell suspension prepared freshly was injected into the lesioned corpus striatum of rats in cell grafted group, and 4μL D-Hank＇s solution was injected in sham transplantation group in the same way. There was no injection in control group. Apomorphine-induced rotation rate of PD rats were recorded respectively in cell grafted group and sham transplantation group pre-operation （initial value） and at postoperative 2, 4, 6 and 16 weeks. Apomorphine-induced rotation rate of PD rats was recorded in control group at postoperative 2 months （initial value） and following 2,4,6 and 16 weeks. To determine TH antigen with immunohistological ABC method （DAB developing） at 6 months post-transplantation to investigate the differentiation and survival of donor cells in the host body.MAIN OUTCOME MEASURES： Apomorphine-induced rotation behavior before and after transplantation and the survival and differentiation of implanted cells in the host body at 6 months post-transplantation. RESULTS： Among 19 model rats, one rat died after transplantation respectively in the cell grafted group and sham transplantation group; finally 17 model rats entered the stage of result analysis. Relative apomorphine-induced rotation rate was significantly decreased in the cell grafted group as compared with that before transplantation , with significant difference （P 〈 0.01 .P 〈 0.05）;the mean value of relative apomorphine-induced rotation rate was significantly decreased at postoperative 16 weeks in cell grafted group as compared with that of corresponding relative rotation rate in control group , also with significant difference （P 〈 0.05）.Immunohistological results showed that donor cells could differentiate into large and multi-polar dopaminergic neurons in the host body. CONCLUSION ： Primary cultured embryonic MPCs can be used as the donor cells in CRT for treating PD.展开更多
基金supported by National Key Research and Development Program of China(contract No.2019YFA0904800)National Nature Science Foundation of China(32030065,31722033,92049304 to Y.Z.)+5 种基金Shanghai Sailing Program(contract No.21YF1410300)Science and Technology Commission of Shanghai Municipality(contract No.10DZ2220500)The Shanghai Committee of Science and Technology(grant No.11DZ2260600)Shanghai Frontiers Science Center of Optogenetic Techniques for CellMetabolism(Y.Z.)Research Unit of New Techniques for Live-cell Metabolic Imaging(Chinese Academy of Medical Sciences,2019-I2M-5-013 to Y.Z.)the State Key Laboratory of Bioreactor Engineering,the Fundamental Research Funds for the Central Universities.
文摘Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focused on the production and pharmacological side effects caused by H_(2)S.Therefore,effective strategies to remove H_(2)S has become a key research topic.Furthermore,the development of novel nanoplatforms has provided new tools for the targeted removal of H_(2)S.This paper was performed to review the association between H_(2)S anddisease,relatedH_(2)S inhibitory drugs,aswell as H_(2)S responsive nanoplatforms(HRNs).This review first analyzed the role of H_(2)S in multiple tissues and conditions.Second,common drugs used to eliminate H_(2)S,as well as their potential for combination with anticancer agents,were summarized.Not only the existing studies on HRNs,but also the inhibition H_(2)S combined with different therapeutic methods were both sorted out in this review.Furthermore,this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail.Finally,potential challenges of HRNs were proposed.This study demonstrates the excellent potential of HRNs for biomedical applications.
文摘Aqueous and hydro-alcoholic extracts of Achillea fragrantissima L. (Asteraceae) grown in Jordan were screened for their antioxidant, antimicrobial, antiplatelet, anti-proliferative and acetylcholinesterase (AChE) inhibition efficacy. Total phenols and flavonoids were determined colorimetrically. The radical scavenging activities were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical scavenging activity assays. High performance liquid chromatography-mass spectrometry (HPLCMS) analysis resulted in the identification of 7 phenolic compounds in the hydro-alcoholic extract and 4 compounds in the aqueous extract;quercetin 3-β-D-glucoside was the main component for both extracts. Antimicrobial activities were determined by antimicrobial susceptibility testing such as agar well-diffusion method, minimum inhibition concentration and minimum bactericidal concentration. Gram positive bacteria showed sensitivity to hydro-alcoholic extract in the agar-well diffusion test. No significant activity was observed against gram negative bacteria and Candida albicans. Hydro-alcoholic extract had a bactericidal activity against Streptococcus pneumoniae and Bacillus cereus at high concentrations (MIC 12.5 mg/ml) rather than inhibitory effect. In vitro antiplatelet activity was tested on human whole blood using an electrical impedance method. At concentrations (50, 100, and 200 μg/ml), no effect on platelet aggregation was noticed. Anti-proliferative activity was investigated using the MTT assay. At concentrations up to 200 μg/ml, extracts did not possess cytotoxic activity against the MCF-7 cells. Acetylcholinesterase (AChE) inhibitory capacity of A. fragrantissima extracts was tested using TLC assay method, and neither aqueous, nor hydroalcoholic extracts showed AChE inhibition. The present investigation supported the traditional use of A. fragrantissima in the Jordanian folk medicine as an antimicrobial active representative of the genus Achillea. A. fragrantissima extracts should be further studied for their potential use in preventing/treating diseases in which oxidative stress is a part of the pathophysiology.
基金Supplementary information is linked to the online version of the paper on the Cell Research website.Acknowledgments We thank Dr David Westaway （University of Alberta） for TgCRND8 mice, Dr David Baltimore （California Institute of Technology） for lentiviral constructs, Dr Raphael Kopan （Washington University） for the plasmid of myc-tagged NotchAE and Dr Johan Lundkvist （Karolinska Institutet） for the plasmid of Gal4-driven luciferase reporter gene, the plasmid of APP/CTFI3-GVP and NAE-GVP. We appreciate Shunmei Xin, Shan Chen and Xianglu Zeng for their technical assistance. We thank all members of the lab for sharing reagents and advice. This research was supported by the Ministry of Science and Technology （2009ZX09103-684）, the National Natural Science Foundation of China （30621091, 30625014, 30623003, 30871285 and 90713047）, the Shanghai Municipal Commission for Science and Technology （07PJ14099 and 09JC1416400）, and the Chinese Academy of Sciences （2007KIP204）.
基金Acknowledgments This work is supported by the National Natural Science Foundation of China （project 30321002 and 30471580）, Shanghai E-research Institutes, and Science and Technology Commission of Shanghai Municipality （project 04DZ14902）.
基金Abbreviations： double-stranded RNA （dsRNA） ELONGATED UPPER- MOST INTERNODE （Eui）+5 种基金 gibberellin （GA） GIBBERELLIN INSENSI- TIVE DWARF （GID） overexpression （OX） RNA interference （RNAi） slender rice （SLR） wild type （WT） We are grateful to Dr Shinjiro Yamaguchi （RIKEN, Ja- pan） for critical reading of the manuscript, and to Professor Yinong Yang （Penn. State University, USA） for the rice RNAi vector. This work was supported by grants from the National Natural Science Foundation of China （30670186 and 30421001）, and the Ministry of Science and Technology of China （2006AA10A102） to ZH.
文摘米饭 Eui (伸长最高节间) 基因编码撤销的细胞色素 P450 monooxygenase 简历活跃赤霉素(气体) 。在这研究，我们在植物开发调查了 Eui 基因和它的角色的控制表示。我们发现 Eui 是外长的气体导致的差别并且 Eui 倡导者在维管束举办了最高的活动。eui 异种在在根冠的淀粉小粒开发是有缺点的，在表达式上的 Eui 提高了淀粉小粒产生和严肃回答，揭示为在根淀粉小粒开发和严肃回答的 GA 的一个角色。使用胚胎更少一半种子的实验揭示了那 RAmy1A， GAmyb 是高度起来当外长的 GA 不在时在 eui 糊粉房间调整了。另外， GA 生合成基因 GA3ox1 和 GA20ox2 是调整的 down， GA2ox1 起来在 eui 调整了幼苗。这些结果显示 EUI 涉及 GA 动态平衡，不是在仅仅内部在出发阶段的节点，而且在苗期，根和种子。扰乱 GA 动态平衡影响了表明基因 GID1 (赤霉素感觉迟钝的矮子 1 ) 的 GA 的表示， GID2 和 SLR1。有效地增加的 Eui 基因的转基因的 RNA 干扰种高度和改进标题性能。由对比，在米饭 GA 生合成基因 GA3ox2 和 GA20ox2 的倡导者下面的 Eui 的宫外的表示显著地减少了植物高度。这些结果证明 Eui 表示的细微增加能戏剧性地改变米饭形态学，显示在米饭的 Eui 基因的实际申请为一个高产潜力的分子的繁殖。
基金supported by grants from the National Natural Science Foundation of China(Nos.30630041,90208009)the Ministry of Science and Technology of China(No.04JC14077)the Shanghai Scientific Committee(No.KSCX2-YW-N-016)to H Huang.
文摘Traditional Chinese medicine (TCM) is deeply rooted in ancient Chinese culture and has been practiced by Chinese people for thousands of years in order to maintain their health and fight against disease. This ancient Chinese wisdom has accumulated from the long struggle to cope with various diseases through hundreds or even thousands of trial-and-error practices. However, due to its empirical character, TCM has long been criticized as being deficient in scientific evidence, and is still not widely accepted by the mainstream conventional medical system. The complexity of the chemical components of TCM and the clarification of its mechanisms remain an enormous challenge in the conversion of TCM into an evidence-based medicine. Thanks to incredible progress in biomedical research, TCM has evolved at an astonishing pace in various aspects, as indicated by the 2015 Nobel Prize awarded to Professor Youyou Tu for her discovery of artemisinin.
基金Acknowledgments The authors thank Qiongping Huang, Lirong Liu, and Wei Bian for technical assistance. We are grateful to Drs G Chan （Cross Cancer Institute, University of Alberta, Edmonton Alberta, Canada） for antibodies to human ZW 10 and Rod, KH Choo （Murdoch Children＇s Research Institute, Royal Children＇s Hospital, Melbourne, Australia） for anti-CREST serum, and E Fuchs （Rockefeller University, USA） for mRFP cDNA. This work was supported by the National Science Foundation of China （30330330, 30421005, and 30623003）, Ministry of Science and Technology of China （2005CB522703 and 2007CB914501）, and the Shanghai Municipal Council for Science and Technology （S048014317, 06DZ22032, and 058014578）.
文摘Recent progress in bioinorganic chemistry studies of rare earth elements (REE) in animal cells was outlined, and the definition of REE′s biological intelligence as well as their mechanism were also explained. The migration of REE from weathering rocks to the environment is accelerated by various anthropogenic activities, which can eventually result in the entrance of REE into animal and human bodies via food chain. REE can be found in body tissues such as brain, blood, muscle as well as bone. Based on their geochemical properties, REE in low dose show their unique biological intelligence by intervening in the process of signal transduction and its regulation, arteriosclerosis and blood clotting prevention, anticancer, and the promotion of cellular defense enzymes′ activities, nucleic acid metabolism enzymes as well as ATPases, etc. The meaning of REE′s biological intelligence refers to physicochemical properties-based capability to choose the targets (e.g., biometals) in biomolecules for the chelation or replacement of REE, and change the structures and functions of biomolecules, and consequently impact or control the biological functions or behaviors in living organisms. The regulation of various cellular processes caused by REE is mainly via antagonism or replacement of essential target biometals like calcium or via chelation of organic molecules, thereby embodying the unparalleled biological intelligence of REE. Additionally, the dosage effect of REE was also discussed from the angles of yin-yang dichotomy, bioavailability, entropy and evolution. In order to make full use of REE′s biological intelligence in the application for medicine, more detailed studies concerning dosage effect of REE and REE bioaccumulation in organisms should be conducted in future research.
文摘BACKGROUND： Choosing proper donor cells is one of keys in experimental and clinical studies on cell replacement therapy （CRT） for treating Parkinson disease （PD）. Embryonic mesencephalic precursor cells （MPCs） can stably differentiate into dopaminergic neuron after in vitro proliferated culture. As compared with embryonic stem cell and neural stem cell strains, cell composition of embryonic MPCs after primary culture is also the most close to that of embryonic mesencephalic ventral cell suspension without proliferated culture. Successful experience accumulated in the latter suggests that primary cultured embryonic MPCs might be the most potential donor cells in clinical application with CRT for treating PD so far. OBJECTIVE： To investigate the feasibility of primary cultured embryonic precursor cells cultured primarily as donor cells in CRT for treating PD in rats. DESIGN ： A randomized and controlled trial taking SD rats as experimental animals.SETTING： Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University.MATERIALS： This experiment was carried out at the Institute of Neuroscience, Shanghai Institute for Biological Science, Chinese Academy of Sciences from July 2003 to June 2004. Totally 26 female SD rats, with body mass of 200 to 220 g, were provided by Shanghai Experimental Animal Center of Chinese Academy of Sciences. METHODS ： Stereotaxic injection of 6-hydroxydopamine into the medial forebrain bundle were perfored to develop PD model rat. Among 26 SD rats, 20 rats achieved a more than 5 turns/min in apomorphine induced rotation test, reaching the standard of PD model rats. Immunohistochemical detection was performed on 1 out of 20 model rats after execution, and the other 19 rats were randomly divided into control group （n=5）, sham transplantation group （n=5）and cell grafted group （n=9）. Primary cultured E12 MPC cell suspension （1.2×10^11 L^-1）were used as donor cells. 4μL primary cultured E12 MPC cell suspension prepared freshly was injected into the lesioned corpus striatum of rats in cell grafted group, and 4μL D-Hank＇s solution was injected in sham transplantation group in the same way. There was no injection in control group. Apomorphine-induced rotation rate of PD rats were recorded respectively in cell grafted group and sham transplantation group pre-operation （initial value） and at postoperative 2, 4, 6 and 16 weeks. Apomorphine-induced rotation rate of PD rats was recorded in control group at postoperative 2 months （initial value） and following 2,4,6 and 16 weeks. To determine TH antigen with immunohistological ABC method （DAB developing） at 6 months post-transplantation to investigate the differentiation and survival of donor cells in the host body.MAIN OUTCOME MEASURES： Apomorphine-induced rotation behavior before and after transplantation and the survival and differentiation of implanted cells in the host body at 6 months post-transplantation. RESULTS： Among 19 model rats, one rat died after transplantation respectively in the cell grafted group and sham transplantation group; finally 17 model rats entered the stage of result analysis. Relative apomorphine-induced rotation rate was significantly decreased in the cell grafted group as compared with that before transplantation , with significant difference （P 〈 0.01 .P 〈 0.05）;the mean value of relative apomorphine-induced rotation rate was significantly decreased at postoperative 16 weeks in cell grafted group as compared with that of corresponding relative rotation rate in control group , also with significant difference （P 〈 0.05）.Immunohistological results showed that donor cells could differentiate into large and multi-polar dopaminergic neurons in the host body. CONCLUSION ： Primary cultured embryonic MPCs can be used as the donor cells in CRT for treating PD.
基金The authors thank Mr Qin Peng Mong, Xiao Feng Li, Satoshi Tabata, Shusei Sato and Jun Yang for their help to conduct the experiment, and Dr Liang Huang for helpful revision of the manuscript. This research was financially supported by the National Natural Science Foundation of China （Grant No. 30430330）.
基金Acknowledgments We thank Drs Hua Gu （Columbia University, USA）, Weiguo Zhang （Duke University Medical Center, USA）, and Youhai H Chen （University of Pennsylvania, USA） for reviewing the manuscript and for suggestions, and Dr Ilia Voskoboinik （Peter MacCallum Cancer Centre, Australia） for providing the mouse perforin cDNA in pKS（＋） Bluescript. Ragl^-/- mice were gifts from Xiaolong Liu （Shanghai Institutes for Biological Sciences, China）. This work was supported by grants from the National Natural Science Foundation of China （30325018, 30530700, 30623003, and 30421005） and CAS project （KSCX1-YW-R-43）, grants from the National Key Project 973 （2006CB504300 and 2007CB512404）, grants from the Technology Commission of Shanghai Municipality （04DZ14902, 04DZ19108, 06DZ22032, 04DZ19112, 07XD14033, and 07DZ22916）, 863 key project （2006AA02A247）, and a grant from the E-institutes of Shanghai Universities Immunology Division.
文摘Perforin 是主要从事调停的形成毛孔的蛋白质目标 T 房间死亡并且被细胞毒素的 T 淋巴细胞(CTL ) 和自然漂亮房间采用。然而，它是否也在常规 CD4+ T 房间功能起一个作用，仍然保持不清楚。这里，我们报导那在 perforin 缺乏(PKO ) 老鼠， CD4+ T 房间是响应 T 的 hyperproliferative 房间受体(TCR ) 刺激。hyperproliferation 的这个特征被改进在房间分割并且在 IL-2 分泌物伴随。看起来， perforin 缺乏不在胸腺怒气和淋巴节点影响 T 房间开发。在 vivo， perforin 缺乏导致增加的抗原特定的 T 房间增长和抗体生产。而且， PKO 老鼠更产生试验性的自体免疫的眼色素层炎。探讨分子的机制，我们发现在 TCR 刺激以后，从 PKO 老鼠的 CD4+ T 房间显示增加的细胞内部的钙流动并且随后提高抄写因素 NFAT1 的激活。我们的结果显示 perforin 在由影响 TCR 依赖的 Ca2+ 发信号调整 CD4+ T 房间激活和有免疫力的反应起一个否定作用。
