OBJECTIVE: To evaluate the effect of Tanreqing injection on axon myelin in the mouse brain of experimental autoimmune encephalomyelitis(EAE).METHODS: An EAE model was established by myelin oligodendrocyte glycoprotein...OBJECTIVE: To evaluate the effect of Tanreqing injection on axon myelin in the mouse brain of experimental autoimmune encephalomyelitis(EAE).METHODS: An EAE model was established by myelin oligodendrocyte glycoprotein(MOG)35-55 immunization in C57BL/6 mice. Mice were randomly divided into the following groups: normal, model,prednisone acetate(PA)(6 mg/kg), Tanreqing high dose(5.14 m L/kg), Tanreqing low dose(2.57 m L/kg). On the day of immunization, both Tanreqing groups were treated by intraperitoneal injection,with the PA group treated by intragastrical perfusion after T cell response, and the other groups treated with saline. Changes in body weight, neurological deficit score, incidence rate, mortality rate,and course of disease were observed for all mice.Brain tissue was isolated and stained with hematoxylin-eosin, and pathological investigations performed to evaluate axon myelin damage by transmission electron microscopy(TEM). Myelin basic protein and microtubule associated protein-2 were analyzed by immunohistochemistry.RESULTS: Tanreqing injection significantly prolonged EAE latency and decreased the neurological deficit score, alleviated infiltration of inflammatory cells in the focus area, up-regulated hippocampal MBP expression at the acute stage and the remission stage, and increased microtubule associated protein-2 expression in the EAE brain to varying degrees in the acute stage. TEM analysis indicated that Tanreqing injection alleviates myelin damage in the EAE mouse and maintains the integrity of circular layer structures and alleviates axon mitochondrial swelling.CONCLUSION: Tanreqing injection alleviates EAE symptoms.展开更多
AIM： To clarify differences in mucin phenotype, prolif- erative activity and oncogenetic alteration among sub- types of colorectal laterally spreading tumor （LST）. METHODS： LSTs, defined as superficial elevated le...AIM： To clarify differences in mucin phenotype, prolif- erative activity and oncogenetic alteration among sub- types of colorectal laterally spreading tumor （LST）. METHODS： LSTs, defined as superficial elevated lesions greater than 10 mm in diameter with a low vertical axis, were macroscopically classified into two subtypes： （1） a granular type （Gr-LST） composed of superficially spread- ing aggregates of nodules forming a fiat-based lesion with a granulonodular and uneven surface; and （2） a non-granular type （NGr-LST） with a flat smooth surface and an absence of granulonodular formation. A total of 69 LSTs, comprising 36 Gr-LSTs and 33 NGr-LSTs, were immunohistochemically stained with MUC2, MUC5AC, MUC6, CD10 （markers of gastrointestinal cell lineage）, p53, 13-catenin and Ki-67 antibodies, and examined for alteration in exon 1 of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog （KRAS） and exon 15 of v-raf murine sarcoma viral oncogene homologue B1 （BRAF） by poly- merase chain reaction followed by direct sequencing. RESULTS： Histologically, 15 Gr-LST samples were ad- enomas with low-grade dysplasia （LGD）, 12 were high- grade dysplasia （HGD） and 9 were adenocarcinomas invading the submucosa （INV）, while 12 NGr-LSTs demonstrated LGD, 14 HGD and 7 INV. In the proximal colon, MUC5AC expression was significantly higher in the Gr-type than the NGr-type. MUC6 was expressed only in NGr-LST. MUC2 or CD10 did not differ. P53 ex- pression demonstrated a significant stepwise increment in progression through LGD-HGD-INV with both types of LST. Nuclear β-catenin expression was significantly higher in the NGr-type. Ki-67 expression was signifi- cantly higher in the Gr-type in the lower one third zone of the tumor. In proximal, but not distal colon tumors, the incidence of KRAS provided mutation was signifi- cantly higher in the Gr-type harboring a specific muta- tional pattern （G12V）. BRAF mutations （V600E） were detected only in two Gr-LSTs. CONCLUSION： The two subtypes of LST, especially in the proximal colon, have differing phenotypes of gastrointestinal cell lineage, proliferation and activa- tion of Wnt/β-catenin or RAS/RAF/extracellular signal- regulated kinase signaling.展开更多
OBJECTIVE:To study the effect of methotrexate(MTX) combined with Sanhuang Yilong decoction(SYD) on aquaporin(AQP) expression,and to explore the role of AQPs in the pathogenesis of rheumatoid arthritis(RA).METHODS:A to...OBJECTIVE:To study the effect of methotrexate(MTX) combined with Sanhuang Yilong decoction(SYD) on aquaporin(AQP) expression,and to explore the role of AQPs in the pathogenesis of rheumatoid arthritis(RA).METHODS:A total of 118 dampness-heat blockage type RA patients who were hospitalized in the General Chengdu Military Hospital between January2014 and December 2016 were selected as subjects in this study(30 patient of these patients with knee joint effusion were assigned to the RA synovial fluid group).For the pre-treatment controlgroups,30 healthy volunteers were recruited as the healthy control group and 30 osteoarthritis(OA) patients with knee joint effusion were included as OA synovial fluid control group.The RA dampnessheat blockage syndrome treatment groups were divided into 45 cases in the combined group and 45 cases in the MTX group.The combined group received MTX combined with SYD treatment while the MTX group received MTX alone.AQP1,AQP2 and AQP3 expressions were detected in the serum and synovial fluid.RESULTS:AQP1 had the highest expression,followed by AQP3,and AQP2.The serum levels of AQP1,AQP2 and AQP3 were all significantly lower than those in the healthy volunteers(P < 0.05),while the synovial fluid AQP1,AQP2 and AQP3 expression in the RA group were comparable to these in the OA groups(P > 0.05).After treatment for2 weeks,serum AQP1,AQP2,AQP3 were significantly increased and erythrocyte sedimentation rate,C-reactive protein,disease activity score of 28 joints were decreased in the combined group(P < 0.05).CONCLUSION:Abnormal expression of AQPs inhibits water metabolism in RA dampness-heat blockage syndrome,so liquid is accumulated at the joint,which may play an important role in the pathogenesis of RA.MTX combined with SYD for the treatment of RA can effectively increase AQP expression.展开更多
Metformin may reduce food intake and body weight, but the anorexigenic effects of metformin are still poorly understood. In this study, Sprague-Dawley rats were administered a single intracere- broventricular dose of ...Metformin may reduce food intake and body weight, but the anorexigenic effects of metformin are still poorly understood. In this study, Sprague-Dawley rats were administered a single intracere- broventricular dose of metformin and compound C, in a broader attempt to investigate the regula- tory effects of metformin on food intake and to explore the possible mechanism. Results showed that central administration of metformin significantly reduced food intake and body weight gain, par- ticularly after 4 hours. A reduction of neuropeptide Y expression and induction of AMP-activated protein kinase phosphorylation in the hypothalamus were also observed 4 hours after metformin administration, which could be reversed by compound C, a commonly-used antagonist of AMP-activated protein kinase. Furthermore, metformin also improved lipid metabolism by reducing plasma low-density lipoprotein. Our findings suggest that under normal physiological conditions, central regulation of appetite by metformin is related to a decrease in neuropeptide Y gene expres- sion, and that the activation of AMP-activated protein kinase may simply be a response to the anorexigenic effect of metformin.展开更多
OBJECTIVE: To investigate the underlying mechanism of reduced myocardial ischemia-reperfusion (I/R) injury in rats using the traditionalTibetan medicine Sanweitanxiang powder (SWTX). METHODS: Rats were randomly divide...OBJECTIVE: To investigate the underlying mechanism of reduced myocardial ischemia-reperfusion (I/R) injury in rats using the traditionalTibetan medicine Sanweitanxiang powder (SWTX). METHODS: Rats were randomly divided into six groups (n=10) as follows: (a) propranolol dinitrate control group, given propranolol dinitrate 0.02 g/kg for 10 days before I/R, (b) SWTX with a high dose group, given SWTX 1.5 g/kg for 10 days before I/R, (c) SWTX with a medium dose group, given SWTX 1.25 g/kg for 10 days before I/R, (d) sham group (Sham), in which the rat heart was exposed by pericardiotomy but without I/R, (e) SWTX with a low dose group, given SWTX 1.0 g/kg for 10 days before I/R, and (f) I/R injury group. Rats were intragastrically pretreated with propranolol dinitrate orSWTX. After that, the operation to cause ischemia and reperfusion was conducted.The histopathologic changes of rat hearts were observed by hematoxylin and eosin staining and transmission electron microscopy. Ca2+ homeostasis protein expression was determined by western blot. RESULTS: After SWTX pretreatment, the development of ultrastructural pathological changes from IR injury was attenuated. A decrease in the expression of B-cell lymphoma 2 associated X protein, and an increase in the expression of B-cell lymphoma 2 were observed. An increased activation of extracellular signal regulated kinases were found. Compared with the sham group, the expression of sarcoplasmic reticulum calcium-ATPase, phospholamban, and calsequestrin were all up-regulated after pretreatment with SWTX. CONCLUSION: The protective mechanism of SWTX pretreatment on myocardial I/R injury might be related to its effect on maintaining the balance of calcium homeostasis in rat heart.展开更多
In order to add value to potato peels and also curb their environmental pollution problems, this study investigated the protein enrichment of potato peels with Saccharomyces cerevisiae via Solid-State Fermentation (SS...In order to add value to potato peels and also curb their environmental pollution problems, this study investigated the protein enrichment of potato peels with Saccharomyces cerevisiae via Solid-State Fermentation (SSF). SSF is a fermentation process which involves solid matrix and is carried out in absence or near absence of free water. SSF of potato peel mashed was carried out with S. cerevisiae at 30°C, pH of 5.5, moisture adjustment between 40 and 90%, addition of ammonium sulphate and urea salts as nitrogen supplements for the microorganisms for 3 days. The results showed that the percentage crude protein content of all the fermented samples increased significantly when compared with the unfermented sample. 40% moisture content adjustment and ammonium sulphate as nitrogen source gave the best result. The crude protein increased from 12.5% to 21.86%, which is 74.88% increment for ammonium sulphate supplementation, and 12.5% to 18.42%, which is 47% increment for urea supplementation. Therefore, the fermented peels could serve as good source of cheap protein enriched feed for livestock.展开更多
目的探索血浆热休克蛋白70(heat shock protein 70,HSP70)作为军事应激负荷生物标志物的可行性。方法采用ELISA方法检测海军某部执行长远航任务6个月后官兵血浆中的HSP70水平的变化,采用应激评定问卷和自测健康评定量表调研其应激负荷...目的探索血浆热休克蛋白70(heat shock protein 70,HSP70)作为军事应激负荷生物标志物的可行性。方法采用ELISA方法检测海军某部执行长远航任务6个月后官兵血浆中的HSP70水平的变化,采用应激评定问卷和自测健康评定量表调研其应激负荷及健康状态。结果与未执行任务组相比,执行长远航任务官兵血浆HSP70水平升高31.40%,思维和焦虑水平、负性情绪、躯体症状指标均显著高于正常水平,生理健康、心理健康和社会健康状况低于正常水平,血浆HSP70水平的升高与应激水平的升高密切相关。结论血浆HSP70水平可作为军事应激负荷评价的重要指标,为军事应激损伤预警提供科学支撑。展开更多
Subcellular localization of proteins can provide key hints to infer their functions and structures in cells. With the breakthrough of recent molecule imaging techniques, the usage of 2D bioimages has become increasing...Subcellular localization of proteins can provide key hints to infer their functions and structures in cells. With the breakthrough of recent molecule imaging techniques, the usage of 2D bioimages has become increasingly popular in automatically analyzing the protein subcellular location pat- terns. Compared with the widely used protein 1D amino acid sequence data, the images of protein distribution are more intuitive and interpretable, making the images a better choice at many applications for revealing the dynamic char- acteristics of proteins, such as detecting protein translocation and quantification of proteins. In this paper, we systemati- cally reviewed the recent progresses in the field of automated image-based protein subcellular location prediction, and clas- sified them into four categories including growing of bioim- age databases, description of subcellular location distribution patterns, classification methods, and applications of the pre- diction systems. Besides, we also discussed some potential directions in this field.展开更多
Herpes simplex virus type 1(HSV-1)is a common hu-man pathogen causing cold sores and even more se-rious diseases.It can establish a latent stage in sensory ganglia after primary epithelial infections,and reacti-vate i...Herpes simplex virus type 1(HSV-1)is a common hu-man pathogen causing cold sores and even more se-rious diseases.It can establish a latent stage in sensory ganglia after primary epithelial infections,and reacti-vate in response to stress or sunlight.Previous studies have demonstrated that viral immediate-early protein ICP0 plays a key role in regulating the balance between lytic and latent infection.Recently,It has been deter-mined that promyelocytic leukemia(PML)nuclear bod-ies(NBs),small nuclear sub-structures,contribute to the repression of HSV-1 infection in the absence of functional ICP0.In this review,we discuss the funda-mentals of the interaction between ICP0 and PML NBs,suggesting a potential link between PML NBs and ICP0 in regulating lytic and latent infection of HSV-1.展开更多
The measles virus (MV) strains with mutated hemagglutinin gene (ha) lost the capacity to infect its sensitive host cells (Vero cells), but it may infect the marmoset B-lymphoblastoid cell line B95a. From above, we can...The measles virus (MV) strains with mutated hemagglutinin gene (ha) lost the capacity to infect its sensitive host cells (Vero cells), but it may infect the marmoset B-lymphoblastoid cell line B95a. From above, we can presume that there is a novel cellular receptor for those measles virus strains on B95a cells. Using the yeast two-hybrid system, we screened and cloned a novel gene-bip (B-lymphoblastoid interaction protein of marmoset) from B95a cell cDNA library, which encoded a protein interacting with measles virus hemagglutinin protein (Ha). The bip cDNA was 1540 base pairs in length and contained a unique open reading frame (ORF) of 1011 base pairs encoding a transmembrane protein of 337 amino acid residues. The primary structure of amino acids residue is predicted that the Bip comprised a hydrophobic transmembrane domain and a hydrophobic leader region. The researches about the deletion mutants showed that the deletion of transmembrane domain in Bip did not affect the interaction between Bip and展开更多
Modern crop varieties display a degree of mismatch between their current distributions and the suitability of the local climate for their productivity.To address this issue,we present Oryza CLIMtools(https://gramene.o...Modern crop varieties display a degree of mismatch between their current distributions and the suitability of the local climate for their productivity.To address this issue,we present Oryza CLIMtools(https://gramene.org/CLIMtools/oryza_v1.0/),thefirst resource for pan-genome prediction of climate-associated genetic variants in a crop species.Oryza CLIMtools consists of interactive web-based databases that enable the user to(1)explore the local environments of traditional rice varieties(landraces)in South-East Asia and(2)investigate the environment by genome associations for 658 Indica and 283 Japonica rice landrace accessions collected from georeferenced local environments and included in the 3K Rice Ge-nomes Project.We demonstrate the value of these resources by identifying an interplay betweenflowering time and temperature in the local environment that is facilitated by adaptive natural variation in OsHD2 and disrupted by a natural variant in OsSOC1.Prior quantitative trait locus analysis has suggested the impor-tance of heterotrimeric G proteins in the control of agronomic traits.Accordingly,we analyzed the climate associations of natural variants in the different heterotrimeric G protein subunits.We identified a coordi-nated role of G proteins in adaptation to the prevailing potential evapotranspiration gradient and revealed their regulation of key agronomic traits,including plant height and seed and panicle length.We conclude by highlighting the prospect of targeting heterotrimeric G proteins to produce climate-resilient crops.展开更多
Heme,as a prosthetic group of proteins,is an iron-protoporphyrin involved in a wide range of cellular functions.Cellular heme levels vary due to the accurate balance of its synthesis and degradation.The“heme sensor p...Heme,as a prosthetic group of proteins,is an iron-protoporphyrin involved in a wide range of cellular functions.Cellular heme levels vary due to the accurate balance of its synthesis and degradation.The“heme sensor protein”is currently a focus of investigation because heme has been found as a cellular signaling messenger involved in various biologic processes,including gene expression,protein localization,protein stability and microRNA processing.Several eukaryotic transcriptional factors can be regulated by heme,including heme activator protein(Hap1),Bach1,REV-erbα,and neuronal PAS domain protein 2(NPAS2).Especially,the two circadian transcrip-tional factors serving as the heme sensor,REV-erbαand NPAS2,coordinate the circadian clock with metabolic pathways.It is well established that heme regulates the activity of heme-regulated eukaryotic initiation factor 2α(eIF2α)kinase(HRI),which serves as a feedback inhibitor of protein translation in both erythroid and non-erythroid cells.Additionally,heme is involved in protein degradation by inducing the degradation of several proteins such as the iron response regulator(Irr),iron regulatory protein 2(IRP2),Bach1,and circadian factor period 2(Per2).The N-end rule ubiquitin-dependent protein degradation path-way has also been identified as a sensor of heme,which blocks the function of arginyl-tRNA protein transferase(ATE1)and E3 ubiquitin ligase.In this review,we summarize the regulatory roles of heme at the levels of transcription,protein translation,and protein degradation,highlighting the role of heme in maintaining cellular homeostasis.展开更多
Insects produce silk to form cocoons,nests,and webs,which are important for their survival and reproduction.However,little is known about the molecular mecha-nism of silk protein synthesis at the translation level.The...Insects produce silk to form cocoons,nests,and webs,which are important for their survival and reproduction.However,little is known about the molecular mecha-nism of silk protein synthesis at the translation level.The solute carrier family 7(SLC7)genes are involved in activating the target of rapamycin complex 1(TORC1)signaling pathway and protein translation process,but the physiological roles of SLC7 genes in silk-producing insects have not been reported.Here,we found that amino acid signaling regulates silk protein synthesis and larval development via the L-type amino acid trans-porter 1(LAT1;also known as SLC7A5)in Bombyx mori.A total of 12 SLC7 homologs were identified in the silkworm genome,among which BmSLC7A5 was found to be a silk gland-enriched gene and may be involved in leucine transport.Bioinformatics analy-sis indicated that SLC7A5 displays high homology and a close phylogenetic relationship in silk-producing insects.Subsequently,we found that leucine treatment significantly in-creased silk protein synthesis by improving the transcription and protein levels of silk genes.Furthermore,systemic and silk gland-specific knockout of BmSLC7A5 led to de-creased silk protein synthesis by inhibiting TORC1 signaling,and somatic mutation also resulted in arrested development from the 5th instar to the early pupal stage.Altogether,our study reveals that BmSLC7A5 is involved in regulating silk protein synthesis and larval development by affecting the TORC1 signaling pathway,which provides a new strategy and target for improving silk yield.展开更多
The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307)phosphor-ylation,protein phosphatase 2A(PP2A)activity,and on tau phosphorylation.Specific Src siRNA was transfected into c...The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307)phosphor-ylation,protein phosphatase 2A(PP2A)activity,and on tau phosphorylation.Specific Src siRNA was transfected into cultured mouse neuroblastoma N2a cells to inhibit the expression of Src protein,and the phosphorylation levels of PP2A Y307 and tau at different sites,as well as PP2A activity were detected at different time points after siRNA transfection.Twelve hours after siRNA transfec-tion,the protein level of Src was dramatically decreased,with decreased PP2A Y307 phosphorylation.However,the total PP2A protein level was also decreased,together with a decreased PP2A activity.Tau was hyperpho-sphorylated at the Ser198/199/202 sites.Multiple factors may be involved in the cellular regulation of PP2A activ-ity.Inhibiting Src expression could induce inactivation of PP2A and tau hyperphosphorylation.展开更多
The aim of this paper is to explore the effects of transfection of Foxp3 gene on the phenotype and function of naive CD4^(+)T cells.The pMSCV-Foxp3 retroviral vec-tor encoding Foxp3 gene was transduced into the PT67 p...The aim of this paper is to explore the effects of transfection of Foxp3 gene on the phenotype and function of naive CD4^(+)T cells.The pMSCV-Foxp3 retroviral vec-tor encoding Foxp3 gene was transduced into the PT67 packaging cell line.Virus-containing supernatant was applied to differentiate CD4^(+)CD25^(-) T cells.The resulting cells were sorted with flow cytometry.The expressions of CD25,CD127,CTLA-4 and the proliferation of trans-fected T cells were examined.The effect of transfected CD4^(+)T cells on the proliferation and cytokine production of CD4^(+)CD25^(-) T cells was examined.Foxp3-gene trans-fected CD4^(+)T cells could express Foxp3 and transfection of Foxp3 gene up-regulated the expressions of CD25 and CTLA-4,but down-regulated CD127 expression.After transfection,the proliferation of CD4^(+)T cells was elimi-nated.Transfected T cells inhibited the proliferation of CD4^(+)CD25^(-) T cells.CD4^(+)CD25^(-) T cells acquired a reg-ulatory phenotype and function after it was transduced with the Foxp3 gene.This suggested a key role of Foxp3 in the generation of CD4^(+)CD25^(+) regulatory T cells.展开更多
基金Supported by the Research on the Effect of Catalpol on the OPCs' Proliferation and Differentiation(No.81173237)Research on the Impact of OPCs and Remyelination via the Method of Bushenyisu with EAE mice(No.81072765)of National Natural Science Foundation
文摘OBJECTIVE: To evaluate the effect of Tanreqing injection on axon myelin in the mouse brain of experimental autoimmune encephalomyelitis(EAE).METHODS: An EAE model was established by myelin oligodendrocyte glycoprotein(MOG)35-55 immunization in C57BL/6 mice. Mice were randomly divided into the following groups: normal, model,prednisone acetate(PA)(6 mg/kg), Tanreqing high dose(5.14 m L/kg), Tanreqing low dose(2.57 m L/kg). On the day of immunization, both Tanreqing groups were treated by intraperitoneal injection,with the PA group treated by intragastrical perfusion after T cell response, and the other groups treated with saline. Changes in body weight, neurological deficit score, incidence rate, mortality rate,and course of disease were observed for all mice.Brain tissue was isolated and stained with hematoxylin-eosin, and pathological investigations performed to evaluate axon myelin damage by transmission electron microscopy(TEM). Myelin basic protein and microtubule associated protein-2 were analyzed by immunohistochemistry.RESULTS: Tanreqing injection significantly prolonged EAE latency and decreased the neurological deficit score, alleviated infiltration of inflammatory cells in the focus area, up-regulated hippocampal MBP expression at the acute stage and the remission stage, and increased microtubule associated protein-2 expression in the EAE brain to varying degrees in the acute stage. TEM analysis indicated that Tanreqing injection alleviates myelin damage in the EAE mouse and maintains the integrity of circular layer structures and alleviates axon mitochondrial swelling.CONCLUSION: Tanreqing injection alleviates EAE symptoms.
基金Supported by A grant-in-aid for General Scientific Research from the Ministry of Education, Science, Sports and Culture to Hiroyuki Mitomi, No. 21590394to Tsuyoshi Saito, No. 23590434, To-kyo, Japan
文摘AIM： To clarify differences in mucin phenotype, prolif- erative activity and oncogenetic alteration among sub- types of colorectal laterally spreading tumor （LST）. METHODS： LSTs, defined as superficial elevated lesions greater than 10 mm in diameter with a low vertical axis, were macroscopically classified into two subtypes： （1） a granular type （Gr-LST） composed of superficially spread- ing aggregates of nodules forming a fiat-based lesion with a granulonodular and uneven surface; and （2） a non-granular type （NGr-LST） with a flat smooth surface and an absence of granulonodular formation. A total of 69 LSTs, comprising 36 Gr-LSTs and 33 NGr-LSTs, were immunohistochemically stained with MUC2, MUC5AC, MUC6, CD10 （markers of gastrointestinal cell lineage）, p53, 13-catenin and Ki-67 antibodies, and examined for alteration in exon 1 of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog （KRAS） and exon 15 of v-raf murine sarcoma viral oncogene homologue B1 （BRAF） by poly- merase chain reaction followed by direct sequencing. RESULTS： Histologically, 15 Gr-LST samples were ad- enomas with low-grade dysplasia （LGD）, 12 were high- grade dysplasia （HGD） and 9 were adenocarcinomas invading the submucosa （INV）, while 12 NGr-LSTs demonstrated LGD, 14 HGD and 7 INV. In the proximal colon, MUC5AC expression was significantly higher in the Gr-type than the NGr-type. MUC6 was expressed only in NGr-LST. MUC2 or CD10 did not differ. P53 ex- pression demonstrated a significant stepwise increment in progression through LGD-HGD-INV with both types of LST. Nuclear β-catenin expression was significantly higher in the NGr-type. Ki-67 expression was signifi- cantly higher in the Gr-type in the lower one third zone of the tumor. In proximal, but not distal colon tumors, the incidence of KRAS provided mutation was signifi- cantly higher in the Gr-type harboring a specific muta- tional pattern （G12V）. BRAF mutations （V600E） were detected only in two Gr-LSTs. CONCLUSION： The two subtypes of LST, especially in the proximal colon, have differing phenotypes of gastrointestinal cell lineage, proliferation and activa- tion of Wnt/β-catenin or RAS/RAF/extracellular signal- regulated kinase signaling.
基金the Army Medical Research Twelfth Five Year Plan Key Project(No.BWS11J06)the Sichuan Provincial Health Department(No.120573)
文摘OBJECTIVE:To study the effect of methotrexate(MTX) combined with Sanhuang Yilong decoction(SYD) on aquaporin(AQP) expression,and to explore the role of AQPs in the pathogenesis of rheumatoid arthritis(RA).METHODS:A total of 118 dampness-heat blockage type RA patients who were hospitalized in the General Chengdu Military Hospital between January2014 and December 2016 were selected as subjects in this study(30 patient of these patients with knee joint effusion were assigned to the RA synovial fluid group).For the pre-treatment controlgroups,30 healthy volunteers were recruited as the healthy control group and 30 osteoarthritis(OA) patients with knee joint effusion were included as OA synovial fluid control group.The RA dampnessheat blockage syndrome treatment groups were divided into 45 cases in the combined group and 45 cases in the MTX group.The combined group received MTX combined with SYD treatment while the MTX group received MTX alone.AQP1,AQP2 and AQP3 expressions were detected in the serum and synovial fluid.RESULTS:AQP1 had the highest expression,followed by AQP3,and AQP2.The serum levels of AQP1,AQP2 and AQP3 were all significantly lower than those in the healthy volunteers(P < 0.05),while the synovial fluid AQP1,AQP2 and AQP3 expression in the RA group were comparable to these in the OA groups(P > 0.05).After treatment for2 weeks,serum AQP1,AQP2,AQP3 were significantly increased and erythrocyte sedimentation rate,C-reactive protein,disease activity score of 28 joints were decreased in the combined group(P < 0.05).CONCLUSION:Abnormal expression of AQPs inhibits water metabolism in RA dampness-heat blockage syndrome,so liquid is accumulated at the joint,which may play an important role in the pathogenesis of RA.MTX combined with SYD for the treatment of RA can effectively increase AQP expression.
基金supported by grants from the National Natural Science Foundation of China,No.31171019 and No.31200820the Opening Project of Shanghai Key Laboratory of Brain Functional Genomics and Key Laboratory of Brain Functional Genomics(East China Normal University)of the Ministry of Education
文摘Metformin may reduce food intake and body weight, but the anorexigenic effects of metformin are still poorly understood. In this study, Sprague-Dawley rats were administered a single intracere- broventricular dose of metformin and compound C, in a broader attempt to investigate the regula- tory effects of metformin on food intake and to explore the possible mechanism. Results showed that central administration of metformin significantly reduced food intake and body weight gain, par- ticularly after 4 hours. A reduction of neuropeptide Y expression and induction of AMP-activated protein kinase phosphorylation in the hypothalamus were also observed 4 hours after metformin administration, which could be reversed by compound C, a commonly-used antagonist of AMP-activated protein kinase. Furthermore, metformin also improved lipid metabolism by reducing plasma low-density lipoprotein. Our findings suggest that under normal physiological conditions, central regulation of appetite by metformin is related to a decrease in neuropeptide Y gene expres- sion, and that the activation of AMP-activated protein kinase may simply be a response to the anorexigenic effect of metformin.
基金Supported by a Grant from the National Natural Sciences Foundation of China(No.81060368)
文摘OBJECTIVE: To investigate the underlying mechanism of reduced myocardial ischemia-reperfusion (I/R) injury in rats using the traditionalTibetan medicine Sanweitanxiang powder (SWTX). METHODS: Rats were randomly divided into six groups (n=10) as follows: (a) propranolol dinitrate control group, given propranolol dinitrate 0.02 g/kg for 10 days before I/R, (b) SWTX with a high dose group, given SWTX 1.5 g/kg for 10 days before I/R, (c) SWTX with a medium dose group, given SWTX 1.25 g/kg for 10 days before I/R, (d) sham group (Sham), in which the rat heart was exposed by pericardiotomy but without I/R, (e) SWTX with a low dose group, given SWTX 1.0 g/kg for 10 days before I/R, and (f) I/R injury group. Rats were intragastrically pretreated with propranolol dinitrate orSWTX. After that, the operation to cause ischemia and reperfusion was conducted.The histopathologic changes of rat hearts were observed by hematoxylin and eosin staining and transmission electron microscopy. Ca2+ homeostasis protein expression was determined by western blot. RESULTS: After SWTX pretreatment, the development of ultrastructural pathological changes from IR injury was attenuated. A decrease in the expression of B-cell lymphoma 2 associated X protein, and an increase in the expression of B-cell lymphoma 2 were observed. An increased activation of extracellular signal regulated kinases were found. Compared with the sham group, the expression of sarcoplasmic reticulum calcium-ATPase, phospholamban, and calsequestrin were all up-regulated after pretreatment with SWTX. CONCLUSION: The protective mechanism of SWTX pretreatment on myocardial I/R injury might be related to its effect on maintaining the balance of calcium homeostasis in rat heart.
文摘In order to add value to potato peels and also curb their environmental pollution problems, this study investigated the protein enrichment of potato peels with Saccharomyces cerevisiae via Solid-State Fermentation (SSF). SSF is a fermentation process which involves solid matrix and is carried out in absence or near absence of free water. SSF of potato peel mashed was carried out with S. cerevisiae at 30°C, pH of 5.5, moisture adjustment between 40 and 90%, addition of ammonium sulphate and urea salts as nitrogen supplements for the microorganisms for 3 days. The results showed that the percentage crude protein content of all the fermented samples increased significantly when compared with the unfermented sample. 40% moisture content adjustment and ammonium sulphate as nitrogen source gave the best result. The crude protein increased from 12.5% to 21.86%, which is 74.88% increment for ammonium sulphate supplementation, and 12.5% to 18.42%, which is 47% increment for urea supplementation. Therefore, the fermented peels could serve as good source of cheap protein enriched feed for livestock.
文摘目的探索血浆热休克蛋白70(heat shock protein 70,HSP70)作为军事应激负荷生物标志物的可行性。方法采用ELISA方法检测海军某部执行长远航任务6个月后官兵血浆中的HSP70水平的变化,采用应激评定问卷和自测健康评定量表调研其应激负荷及健康状态。结果与未执行任务组相比,执行长远航任务官兵血浆HSP70水平升高31.40%,思维和焦虑水平、负性情绪、躯体症状指标均显著高于正常水平,生理健康、心理健康和社会健康状况低于正常水平,血浆HSP70水平的升高与应激水平的升高密切相关。结论血浆HSP70水平可作为军事应激负荷评价的重要指标,为军事应激损伤预警提供科学支撑。
文摘Subcellular localization of proteins can provide key hints to infer their functions and structures in cells. With the breakthrough of recent molecule imaging techniques, the usage of 2D bioimages has become increasingly popular in automatically analyzing the protein subcellular location pat- terns. Compared with the widely used protein 1D amino acid sequence data, the images of protein distribution are more intuitive and interpretable, making the images a better choice at many applications for revealing the dynamic char- acteristics of proteins, such as detecting protein translocation and quantification of proteins. In this paper, we systemati- cally reviewed the recent progresses in the field of automated image-based protein subcellular location prediction, and clas- sified them into four categories including growing of bioim- age databases, description of subcellular location distribution patterns, classification methods, and applications of the pre- diction systems. Besides, we also discussed some potential directions in this field.
基金supported by grants from the State Key Development Program for Basic Research of China(973 Program)(Grant Nos.2010CB530105 and 2011CB504802)The Startup Fund of the 100 Talents Program from the Chinese Academy of Sciences(No.20072020-141)National Natural Science Foundation of China(Grant Nos.30870120,81171584,81101263,and 81000736)。
文摘Herpes simplex virus type 1(HSV-1)is a common hu-man pathogen causing cold sores and even more se-rious diseases.It can establish a latent stage in sensory ganglia after primary epithelial infections,and reacti-vate in response to stress or sunlight.Previous studies have demonstrated that viral immediate-early protein ICP0 plays a key role in regulating the balance between lytic and latent infection.Recently,It has been deter-mined that promyelocytic leukemia(PML)nuclear bod-ies(NBs),small nuclear sub-structures,contribute to the repression of HSV-1 infection in the absence of functional ICP0.In this review,we discuss the funda-mentals of the interaction between ICP0 and PML NBs,suggesting a potential link between PML NBs and ICP0 in regulating lytic and latent infection of HSV-1.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 39970032).
文摘The measles virus (MV) strains with mutated hemagglutinin gene (ha) lost the capacity to infect its sensitive host cells (Vero cells), but it may infect the marmoset B-lymphoblastoid cell line B95a. From above, we can presume that there is a novel cellular receptor for those measles virus strains on B95a cells. Using the yeast two-hybrid system, we screened and cloned a novel gene-bip (B-lymphoblastoid interaction protein of marmoset) from B95a cell cDNA library, which encoded a protein interacting with measles virus hemagglutinin protein (Ha). The bip cDNA was 1540 base pairs in length and contained a unique open reading frame (ORF) of 1011 base pairs encoding a transmembrane protein of 337 amino acid residues. The primary structure of amino acids residue is predicted that the Bip comprised a hydrophobic transmembrane domain and a hydrophobic leader region. The researches about the deletion mutants showed that the deletion of transmembrane domain in Bip did not affect the interaction between Bip and
基金supported by the National Institute of General Medical Sciences of the NIH under award number 5R01GM126079 to S.M.A.NSF-IOS-2122357 to Prof.Philip C.BevilacquaS.M.A.K.J.K.acknowledges support from NIH training grant 5T32GM102057.
文摘Modern crop varieties display a degree of mismatch between their current distributions and the suitability of the local climate for their productivity.To address this issue,we present Oryza CLIMtools(https://gramene.org/CLIMtools/oryza_v1.0/),thefirst resource for pan-genome prediction of climate-associated genetic variants in a crop species.Oryza CLIMtools consists of interactive web-based databases that enable the user to(1)explore the local environments of traditional rice varieties(landraces)in South-East Asia and(2)investigate the environment by genome associations for 658 Indica and 283 Japonica rice landrace accessions collected from georeferenced local environments and included in the 3K Rice Ge-nomes Project.We demonstrate the value of these resources by identifying an interplay betweenflowering time and temperature in the local environment that is facilitated by adaptive natural variation in OsHD2 and disrupted by a natural variant in OsSOC1.Prior quantitative trait locus analysis has suggested the impor-tance of heterotrimeric G proteins in the control of agronomic traits.Accordingly,we analyzed the climate associations of natural variants in the different heterotrimeric G protein subunits.We identified a coordi-nated role of G proteins in adaptation to the prevailing potential evapotranspiration gradient and revealed their regulation of key agronomic traits,including plant height and seed and panicle length.We conclude by highlighting the prospect of targeting heterotrimeric G proteins to produce climate-resilient crops.
基金funded by the National Key Basic Research Foundation of China(No.2006CB910301)the National Natural Science Foundation of China(Grant No.30930022)+1 种基金the Postdoctoral Science Foundation of China,the Postdoctoral Foundation of Shanghai,the Postdoctoral Foundation of Shanghai Institutes for Biological Sciences(SIBS)K.C.Wong Postdoctoral Fellowship of the Chinese Academy of Sciences,and Sanofi-Aventis-SIBS Postdoctoral Fellowship.
文摘Heme,as a prosthetic group of proteins,is an iron-protoporphyrin involved in a wide range of cellular functions.Cellular heme levels vary due to the accurate balance of its synthesis and degradation.The“heme sensor protein”is currently a focus of investigation because heme has been found as a cellular signaling messenger involved in various biologic processes,including gene expression,protein localization,protein stability and microRNA processing.Several eukaryotic transcriptional factors can be regulated by heme,including heme activator protein(Hap1),Bach1,REV-erbα,and neuronal PAS domain protein 2(NPAS2).Especially,the two circadian transcrip-tional factors serving as the heme sensor,REV-erbαand NPAS2,coordinate the circadian clock with metabolic pathways.It is well established that heme regulates the activity of heme-regulated eukaryotic initiation factor 2α(eIF2α)kinase(HRI),which serves as a feedback inhibitor of protein translation in both erythroid and non-erythroid cells.Additionally,heme is involved in protein degradation by inducing the degradation of several proteins such as the iron response regulator(Irr),iron regulatory protein 2(IRP2),Bach1,and circadian factor period 2(Per2).The N-end rule ubiquitin-dependent protein degradation path-way has also been identified as a sensor of heme,which blocks the function of arginyl-tRNA protein transferase(ATE1)and E3 ubiquitin ligase.In this review,we summarize the regulatory roles of heme at the levels of transcription,protein translation,and protein degradation,highlighting the role of heme in maintaining cellular homeostasis.
基金Thiswork was supported bygrants fromthe NationalNaturalScience FoundationofChina(31772532)the China Postdoctoral Science Foundation(2022MD713704)the Chongqing Science and Technology Bureau(cstc2021ljcyj-bshX0222 and jbky20210004).
文摘Insects produce silk to form cocoons,nests,and webs,which are important for their survival and reproduction.However,little is known about the molecular mecha-nism of silk protein synthesis at the translation level.The solute carrier family 7(SLC7)genes are involved in activating the target of rapamycin complex 1(TORC1)signaling pathway and protein translation process,but the physiological roles of SLC7 genes in silk-producing insects have not been reported.Here,we found that amino acid signaling regulates silk protein synthesis and larval development via the L-type amino acid trans-porter 1(LAT1;also known as SLC7A5)in Bombyx mori.A total of 12 SLC7 homologs were identified in the silkworm genome,among which BmSLC7A5 was found to be a silk gland-enriched gene and may be involved in leucine transport.Bioinformatics analy-sis indicated that SLC7A5 displays high homology and a close phylogenetic relationship in silk-producing insects.Subsequently,we found that leucine treatment significantly in-creased silk protein synthesis by improving the transcription and protein levels of silk genes.Furthermore,systemic and silk gland-specific knockout of BmSLC7A5 led to de-creased silk protein synthesis by inhibiting TORC1 signaling,and somatic mutation also resulted in arrested development from the 5th instar to the early pupal stage.Altogether,our study reveals that BmSLC7A5 is involved in regulating silk protein synthesis and larval development by affecting the TORC1 signaling pathway,which provides a new strategy and target for improving silk yield.
基金supported by the National Natural Science Foundation of China(Grant Nos.30500188,30471922 and 30731160621)Gamla Tja¨narinnor Foundation and Gun och Bertil Stohnes Stiftelse.
文摘The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307)phosphor-ylation,protein phosphatase 2A(PP2A)activity,and on tau phosphorylation.Specific Src siRNA was transfected into cultured mouse neuroblastoma N2a cells to inhibit the expression of Src protein,and the phosphorylation levels of PP2A Y307 and tau at different sites,as well as PP2A activity were detected at different time points after siRNA transfection.Twelve hours after siRNA transfec-tion,the protein level of Src was dramatically decreased,with decreased PP2A Y307 phosphorylation.However,the total PP2A protein level was also decreased,together with a decreased PP2A activity.Tau was hyperpho-sphorylated at the Ser198/199/202 sites.Multiple factors may be involved in the cellular regulation of PP2A activ-ity.Inhibiting Src expression could induce inactivation of PP2A and tau hyperphosphorylation.
基金supported by the National Natural Science Foundation of China(Grant No.30470772).
文摘The aim of this paper is to explore the effects of transfection of Foxp3 gene on the phenotype and function of naive CD4^(+)T cells.The pMSCV-Foxp3 retroviral vec-tor encoding Foxp3 gene was transduced into the PT67 packaging cell line.Virus-containing supernatant was applied to differentiate CD4^(+)CD25^(-) T cells.The resulting cells were sorted with flow cytometry.The expressions of CD25,CD127,CTLA-4 and the proliferation of trans-fected T cells were examined.The effect of transfected CD4^(+)T cells on the proliferation and cytokine production of CD4^(+)CD25^(-) T cells was examined.Foxp3-gene trans-fected CD4^(+)T cells could express Foxp3 and transfection of Foxp3 gene up-regulated the expressions of CD25 and CTLA-4,but down-regulated CD127 expression.After transfection,the proliferation of CD4^(+)T cells was elimi-nated.Transfected T cells inhibited the proliferation of CD4^(+)CD25^(-) T cells.CD4^(+)CD25^(-) T cells acquired a reg-ulatory phenotype and function after it was transduced with the Foxp3 gene.This suggested a key role of Foxp3 in the generation of CD4^(+)CD25^(+) regulatory T cells.
