Vitamin B(VB1),including thiamin,thiamin monophosphate(TMP),and thiamin pyrophosphate(TPP),is an essential micronutrient for all living organisms.Nevertheless,the precise function of VB1 in rice remains unclear.Here,w...Vitamin B(VB1),including thiamin,thiamin monophosphate(TMP),and thiamin pyrophosphate(TPP),is an essential micronutrient for all living organisms.Nevertheless,the precise function of VB1 in rice remains unclear.Here,we described a VB1 auxotrophic mutant,chlorotic lethal seedling(cles)from the mutation of OsTH1,which displayed collapsed chloroplast membrane system and decreased pigment content.OsTH1 encoded a phosphomethylpyrimidine kinase/thiamin-phosphate pyrophosphorylase,and was expressed in various tissues,especially in seedlings,leaves,and young panicles.The VB1 content in cles was markedly reduced,despite an increase in the expression of VB1 synthesis genes.The decreased TPP content affected the tricarboxylic acid cycle,pentose phosphate pathway,and de novo fatty acid synthesis,leading to a reduction in fatty acids(C16:0 and C18:0)and sugars(sucrose and glucose)of cles.Additionally,irregular expression of chloroplast membrane synthesis genes led to membrane collapse.We also found that alternative splicing and translation allowed OsTH1 to be localized to both chloroplast and cytosol.Our study revealed that OsTH1 was an essential enzyme in VB1 biosynthesis and played crucial roles in seedling growth and development by participating in fatty acid and sugar metabolism,providing new perspectives on VB1 function in rice.展开更多
In the process of tumor proliferation and metastasis,tumor cells encounter hypoxia,low glucose,acidosis,and other stressful environments.These conditions prompt tumor cells to generate endoplasmic reticulum stress(ERS...In the process of tumor proliferation and metastasis,tumor cells encounter hypoxia,low glucose,acidosis,and other stressful environments.These conditions prompt tumor cells to generate endoplasmic reticulum stress(ERS).As a signal mechanism that mitigates ERS in eukaryotic cells,the unfolded protein response(UPR)pathway can activate cells and tissues,regulating pathological activities in various cells,and maintaining ER homeostasis.It forms the most crucial adaptive and defensive mechanism for cells.However,under the continuous influence of chemotherapy drugs,the quantity of unfolded proteins and erroneous proteins produced by tumor cells significantly increases,surpassing the normal regulatory range of UPR.Consequently,ERS fails to function properly,fostering tumor cell proliferation and the development of drug resistance.This review delves into the study of three UPR pathways(PERK,IRE1,and ATF6),elucidating the mechanisms of drug resistance and research progress in the signal transduction pathway of UPR related to cancers.It provides a profound understanding of the role and relationship between UPR and anti-tumor drugs,offering a new direction for effective clinical treatment.展开更多
Age-related macular degeneration(AMD) is the leading cause of irreversible blindness in the developed world. The quality of life of both patients and families is impacted by this prevalent disease. Previously, macular...Age-related macular degeneration(AMD) is the leading cause of irreversible blindness in the developed world. The quality of life of both patients and families is impacted by this prevalent disease. Previously, macular degeneration had no known effective treatment. Today, vitamins for non-exudative AMD and intravitreal injection of medications for its exudative form are primary forms of current treatment. Modern advances in molecular science give rise to new possibilities of disease management. In the year 2003 the sequencing of the entire human genome was completed. Since that time, genes such as complement factor H, high-temperature requirement factor A1, and age-relateed maculopathy susceptibility 2 have been discovered and associated with a higher risk of AMD. A patient's genetic make-up may dictate the effectiveness of current or future therapeutic options. In addition, utilizing genetic data and incorporating it into new treatments(such as viral vectors) may lead to longer-lasting(or permanent) VEGF blockade and specific targeting of complement related genes. There have also been considerable advances in stem cell directed treatment of AMD. Retinal pigment epithelial(RPE) cells can be derived from human embryonic stem cells, induced pluripotent stem cells, or adult human RPE stem cells. Utilizing animal models of RPE and retinal degeneration, stem cell-derived RPE cells have been successfully implanted into the subretinal space. They have been injected as a cell mass or as a pre-prepared monolayer on a thin membrane. Visual recovery has been demonstrated in a retinal dystrophic rat model. Preliminary data on 2 human subjects also demonstrates possible early visual benefit from transplantation of stem cell-derived RPE. As more data is published, and as differentiation and implantation techniques are optimized, the stabilization and possible improvement of vision in individuals with non-exudative macular becomes a real possibility. We conclude that the technologic advances that continue to unfold in both genetic and stem cell research offer optimism in the future treatment of AMD.展开更多
Objective To explore the effect of acupuncture on the endoplasmic reticulum stress IRE l-CHOP signal pathway and the expression levels of related apoptosis genes in pancreatic tissue of rats with STZ-induced diabetes ...Objective To explore the effect of acupuncture on the endoplasmic reticulum stress IRE l-CHOP signal pathway and the expression levels of related apoptosis genes in pancreatic tissue of rats with STZ-induced diabetes mellitus. Methods Eighty SD rats were selected, among which, 10 were fed with normal diet and taken as blank control group （＂blank group＂ for short）, the other 70 rats were fed with high fat and high glucose food and injected with small dosage of STZ intraperitoneally, and 30 models were established successfully. The models were randomly divided into acupuncture treatment group （~＇acupuncture group＂ for short）, model control group （＂model group＂ for short） and western medicine group （metformin） with 10 rats in each group. After treatment for 4 weeks, RBG, and the expression levels of CHOP, IRE 2, Bax, Bcl-2 protein and mRNA in pancreatic tissue of rats were determined. Result Compared with the conditions before treatment, RBG reduced obviously in the acupuncture group and western medicine group （P〈0.05）, and there was no statistical difference in RBG in the model group and blank group （P〉0.05）; the expression levels of CHOP, IRE 1 and Bax proteins in pancreatic tissue of rats in the model group were significantly higher than those in the blank group （P〈0.05）, the expression results in the acupuncture group and western medicine group were significantly lower than those in model group （P〈0.05）; the expression levels of CHOP, IRE 1 and Bax mRNAs in pancreatic tissue of rats in the model group were significantly higher than those in the blank group （P〈0.01）, the expression results in the acupuncture group and western medicine group were significantly lower than those in the model group （P〈0.01）; the expression level of Bcl-2 protein in the model group was significantly lower than that in the blank group （P〈0.05）, the expression results in the acupuncture group and western medicine group were significantly higher than that in the model group （P〈0.02）; there was no statistical difference between the acupuncture group and western medicine group （P〉0.05）; the expression level of Bcl-2 mRNA in the model group was significantly lower than that in the blank group （P〈0.02）, the expression results in the acupuncture group and western medicine group were significantly higher than that in the model group （P〈0.01）; there was no statistical difference between the acupuncture group and western medicine group （P〉0.05）. Conclusion There was endoplasmic reticulum stress in the pancreatic tissue of rats with STZ-induced diabetes mellitus, and IRE 1-CHOP signal pathway was the main pathway for inhibiting the endoplasmic reticulum stress in the pancreatic tissue. Acupuncture can improve the endoplasmic reticulum stress in pancreatic tissue, inhibit apoptosis genes, and protect the pancreatic tissue through IRE 1-CHOP signal pathway.展开更多
Summary BRI1-ASSOCIATED RECEPTOR KINASE 1 （BAK1） plays critical roles in plant developmental and immune signaling pathways. BAKI and a large number of leucine-rich repeat receptor-like kinases （LRR-RLKs） harbor a ...Summary BRI1-ASSOCIATED RECEPTOR KINASE 1 （BAK1） plays critical roles in plant developmental and immune signaling pathways. BAKI and a large number of leucine-rich repeat receptor-like kinases （LRR-RLKs） harbor a mysterious carboxyl-terminal tail （CT） beyond their kinase domain. In this study we analyzed the biological significance of this CT region using a unique bak~ mutant allele which causes deletion of the CT region. We showed that BAKt CT promotes its kinase activity and is required for pathogen-associated molec- ular pattern （PAMP）-triggered immunity, but it is dispensable for brassinosteroid responses and BAK1/ BKKl-inhibited cell death signaling. Therefore the BAK1 C-terminal tail is differentially required for its functions in development and immunity.展开更多
Pathological bio-mineralization can be induced by diseases such as preeclampsia. Inspired by these naturally occurring bio-mineralization processes, we have designed a process called protein-controlled peptide assembl...Pathological bio-mineralization can be induced by diseases such as preeclampsia. Inspired by these naturally occurring bio-mineralization processes, we have designed a process called protein-controlled peptide assembly tandem peptide- templated bio-mineralization. The technique provides bio-context-associated data on the activity of target proteins, and facilitates the evaluation of protein function in the associated biological microenvironment. It is a bio-mimetic process that leads to the formation of Ag nanoparticle-decorated peptide nanowires, which can offer efficient signal amplification with high sensitivity for biosensing applications. Consequently, high-temperature requirement factor A1 （HtrA1） can be assayed quantitatively in clinical serum samples to offer information for the diagnosis of preeclampsia and the improved treatment of the disease. The results suggest that the process has considerable potential for use in clinical practice.展开更多
Nedd1 (neural precursor cell expressed, developmentally down-regulated gene 1) is an evolutionarily conserved protein that has previously been characterized as a new member
基金supported by the National Natural Science Foundation of China(32170337,31870303)。
文摘Vitamin B(VB1),including thiamin,thiamin monophosphate(TMP),and thiamin pyrophosphate(TPP),is an essential micronutrient for all living organisms.Nevertheless,the precise function of VB1 in rice remains unclear.Here,we described a VB1 auxotrophic mutant,chlorotic lethal seedling(cles)from the mutation of OsTH1,which displayed collapsed chloroplast membrane system and decreased pigment content.OsTH1 encoded a phosphomethylpyrimidine kinase/thiamin-phosphate pyrophosphorylase,and was expressed in various tissues,especially in seedlings,leaves,and young panicles.The VB1 content in cles was markedly reduced,despite an increase in the expression of VB1 synthesis genes.The decreased TPP content affected the tricarboxylic acid cycle,pentose phosphate pathway,and de novo fatty acid synthesis,leading to a reduction in fatty acids(C16:0 and C18:0)and sugars(sucrose and glucose)of cles.Additionally,irregular expression of chloroplast membrane synthesis genes led to membrane collapse.We also found that alternative splicing and translation allowed OsTH1 to be localized to both chloroplast and cytosol.Our study revealed that OsTH1 was an essential enzyme in VB1 biosynthesis and played crucial roles in seedling growth and development by participating in fatty acid and sugar metabolism,providing new perspectives on VB1 function in rice.
文摘In the process of tumor proliferation and metastasis,tumor cells encounter hypoxia,low glucose,acidosis,and other stressful environments.These conditions prompt tumor cells to generate endoplasmic reticulum stress(ERS).As a signal mechanism that mitigates ERS in eukaryotic cells,the unfolded protein response(UPR)pathway can activate cells and tissues,regulating pathological activities in various cells,and maintaining ER homeostasis.It forms the most crucial adaptive and defensive mechanism for cells.However,under the continuous influence of chemotherapy drugs,the quantity of unfolded proteins and erroneous proteins produced by tumor cells significantly increases,surpassing the normal regulatory range of UPR.Consequently,ERS fails to function properly,fostering tumor cell proliferation and the development of drug resistance.This review delves into the study of three UPR pathways(PERK,IRE1,and ATF6),elucidating the mechanisms of drug resistance and research progress in the signal transduction pathway of UPR related to cancers.It provides a profound understanding of the role and relationship between UPR and anti-tumor drugs,offering a new direction for effective clinical treatment.
文摘Age-related macular degeneration(AMD) is the leading cause of irreversible blindness in the developed world. The quality of life of both patients and families is impacted by this prevalent disease. Previously, macular degeneration had no known effective treatment. Today, vitamins for non-exudative AMD and intravitreal injection of medications for its exudative form are primary forms of current treatment. Modern advances in molecular science give rise to new possibilities of disease management. In the year 2003 the sequencing of the entire human genome was completed. Since that time, genes such as complement factor H, high-temperature requirement factor A1, and age-relateed maculopathy susceptibility 2 have been discovered and associated with a higher risk of AMD. A patient's genetic make-up may dictate the effectiveness of current or future therapeutic options. In addition, utilizing genetic data and incorporating it into new treatments(such as viral vectors) may lead to longer-lasting(or permanent) VEGF blockade and specific targeting of complement related genes. There have also been considerable advances in stem cell directed treatment of AMD. Retinal pigment epithelial(RPE) cells can be derived from human embryonic stem cells, induced pluripotent stem cells, or adult human RPE stem cells. Utilizing animal models of RPE and retinal degeneration, stem cell-derived RPE cells have been successfully implanted into the subretinal space. They have been injected as a cell mass or as a pre-prepared monolayer on a thin membrane. Visual recovery has been demonstrated in a retinal dystrophic rat model. Preliminary data on 2 human subjects also demonstrates possible early visual benefit from transplantation of stem cell-derived RPE. As more data is published, and as differentiation and implantation techniques are optimized, the stabilization and possible improvement of vision in individuals with non-exudative macular becomes a real possibility. We conclude that the technologic advances that continue to unfold in both genetic and stem cell research offer optimism in the future treatment of AMD.
基金Supported by National Natural Science Foundation for Youth of China:81202769Construction project"Innovation team of acupuncture theory,technology and application"of the platform for research and innovation in colleges and universitiesin Anhui:2015 TD 033
文摘Objective To explore the effect of acupuncture on the endoplasmic reticulum stress IRE l-CHOP signal pathway and the expression levels of related apoptosis genes in pancreatic tissue of rats with STZ-induced diabetes mellitus. Methods Eighty SD rats were selected, among which, 10 were fed with normal diet and taken as blank control group （＂blank group＂ for short）, the other 70 rats were fed with high fat and high glucose food and injected with small dosage of STZ intraperitoneally, and 30 models were established successfully. The models were randomly divided into acupuncture treatment group （~＇acupuncture group＂ for short）, model control group （＂model group＂ for short） and western medicine group （metformin） with 10 rats in each group. After treatment for 4 weeks, RBG, and the expression levels of CHOP, IRE 2, Bax, Bcl-2 protein and mRNA in pancreatic tissue of rats were determined. Result Compared with the conditions before treatment, RBG reduced obviously in the acupuncture group and western medicine group （P〈0.05）, and there was no statistical difference in RBG in the model group and blank group （P〉0.05）; the expression levels of CHOP, IRE 1 and Bax proteins in pancreatic tissue of rats in the model group were significantly higher than those in the blank group （P〈0.05）, the expression results in the acupuncture group and western medicine group were significantly lower than those in model group （P〈0.05）; the expression levels of CHOP, IRE 1 and Bax mRNAs in pancreatic tissue of rats in the model group were significantly higher than those in the blank group （P〈0.01）, the expression results in the acupuncture group and western medicine group were significantly lower than those in the model group （P〈0.01）; the expression level of Bcl-2 protein in the model group was significantly lower than that in the blank group （P〈0.05）, the expression results in the acupuncture group and western medicine group were significantly higher than that in the model group （P〈0.02）; there was no statistical difference between the acupuncture group and western medicine group （P〉0.05）; the expression level of Bcl-2 mRNA in the model group was significantly lower than that in the blank group （P〈0.02）, the expression results in the acupuncture group and western medicine group were significantly higher than that in the model group （P〈0.01）; there was no statistical difference between the acupuncture group and western medicine group （P〉0.05）. Conclusion There was endoplasmic reticulum stress in the pancreatic tissue of rats with STZ-induced diabetes mellitus, and IRE 1-CHOP signal pathway was the main pathway for inhibiting the endoplasmic reticulum stress in the pancreatic tissue. Acupuncture can improve the endoplasmic reticulum stress in pancreatic tissue, inhibit apoptosis genes, and protect the pancreatic tissue through IRE 1-CHOP signal pathway.
基金Natural Sciences and Engineering Research Council(NSERC)of CanadaCanada Foundation for Innovation(CFI)
文摘Summary BRI1-ASSOCIATED RECEPTOR KINASE 1 （BAK1） plays critical roles in plant developmental and immune signaling pathways. BAKI and a large number of leucine-rich repeat receptor-like kinases （LRR-RLKs） harbor a mysterious carboxyl-terminal tail （CT） beyond their kinase domain. In this study we analyzed the biological significance of this CT region using a unique bak~ mutant allele which causes deletion of the CT region. We showed that BAKt CT promotes its kinase activity and is required for pathogen-associated molec- ular pattern （PAMP）-triggered immunity, but it is dispensable for brassinosteroid responses and BAK1/ BKKl-inhibited cell death signaling. Therefore the BAK1 C-terminal tail is differentially required for its functions in development and immunity.
基金Acknowledgements This work is supported by the National Natural Science Foundation of China （Nos. 81270710, 81070511, and 21235003）, the Key Clinical Specialist Construction Project of China （No. 2013（544）） and the Networking Project of Prepotency Public Service Platform of Jiangsu Province （No. BM2013058）.
文摘Pathological bio-mineralization can be induced by diseases such as preeclampsia. Inspired by these naturally occurring bio-mineralization processes, we have designed a process called protein-controlled peptide assembly tandem peptide- templated bio-mineralization. The technique provides bio-context-associated data on the activity of target proteins, and facilitates the evaluation of protein function in the associated biological microenvironment. It is a bio-mimetic process that leads to the formation of Ag nanoparticle-decorated peptide nanowires, which can offer efficient signal amplification with high sensitivity for biosensing applications. Consequently, high-temperature requirement factor A1 （HtrA1） can be assayed quantitatively in clinical serum samples to offer information for the diagnosis of preeclampsia and the improved treatment of the disease. The results suggest that the process has considerable potential for use in clinical practice.
文摘Nedd1 (neural precursor cell expressed, developmentally down-regulated gene 1) is an evolutionarily conserved protein that has previously been characterized as a new member
