BACKGROUND Qingjie Fuzheng granules(QFGs) are part of a traditional Chinese medicine formula, which has been widely used and found to be clinically effective with few side effects in various cancer treatments, includi...BACKGROUND Qingjie Fuzheng granules(QFGs) are part of a traditional Chinese medicine formula, which has been widely used and found to be clinically effective with few side effects in various cancer treatments, including colorectal cancer(CRC).However, the precise mechanisms and molecular signaling pathways involved in the activity of QFGs' anticancer effect have not been reported in the literature. In this study, we hypothesized that QFGs can inhibit the growth of colorectal cancer cells, and that its mechanism is closely related to one or more intracellular signal transduction pathways.AIM To better evaluate the mechanism underlying the anti-cancer effect of QFGs on the CRC cell lines HCT-116 and HCT-8.METHOD First, we measured cell viability and cytotoxicity by performing MTT and lactate dehydrogenase(LDH) assays. We evaluated the role of QFGs in cell proliferation and apoptosis by assessing colony formation and analyzing Hoechst 33258 staining. Second, cell cycle and apoptosis rates were measured by fluorescence activated cell sorting, and the expression levels of survivin, cyclin D1, CDK4, p21,Bax, Bcl-2, Fas, FasL, and cleaved-caspase-3/-8/-9 were measured by performing western blots and caspase activity assays. Furthermore, inhibitors of caspase-3/-8/-9 were used to elucidate the specific apoptosis pathway induced by QFGs in cancer cells. Finally, activation of the PI3 K/AKT and ERK signaling pathwayswas examined using the western blot assay to investigate the possible mechanism.RESULTS MTT and LDH assays revealed that after 0.5-2.0 mg/mL of QFGs treatment, cell viability was reduced by(6.90% ± 1.03%)–(59.70% ± 1.51%)(HCT-116; P < 0.05)and(5.56% ± 4.52%)–(49.44% ± 2.47%)(HCT-8; P < 0.05), and cytotoxicity was increased from 0.52 ± 0.023 to 0.77 ± 0.002(HCT-116; P < 0.01) and from 0.56 ±0.054 to 0.81 ± 0.044(HCT-8; P < 0.01) compared with the non-QFGs treatment groups. Additionally, colony formation and Hoechst 33258 staining assays showed that QFGs inhibited proliferation and induced apoptosis in CRC cells.QFGs also increased the expression levels of Bax, Fas and FasL, decreased the level of Bcl-2, and stimulated the activation of caspase-3/-8/-9, which were revealed by western blot and caspase activity assays. In contrast, when adding the three caspase inhibitors, the suppression effect of QFGs on cell viability and apoptosis were markedly inhibited. Moreover, QFGs suppressed the phosphorylation levels of PI3 K, AKT and ERK.CONCLUSION These results demonstrated that QFGs can inhibit CRC cell proliferation and induce apoptosis by suppressing the PI3 K/AKT and ERK signaling pathways.展开更多
Newborn ruminants are considered functionally monogastric animals.The poor understanding of cellular differences between newborn and mature ruminants prevents the improvement of health and performance of domestic rumi...Newborn ruminants are considered functionally monogastric animals.The poor understanding of cellular differences between newborn and mature ruminants prevents the improvement of health and performance of domestic ruminants.Here,we performed the single-cell RNA sequencing on the rumen,reticulum,omasum,abomasum,duodenum,jejunum,ileum,cecum,colon,rectum,liver,salivary gland,and mammary gland from newborn and adult cattle.A comprehensive single-cell transcriptomic atlas covering 235,941 high-quality single cells and 78 cell types was deciphered.A Cattle Cell Landscape database(http://cattlecelllandscape.zju.edu.cn)was established to elaborately display the data and facilitate effective annotation of cattle cell types and subtypes for the broad research community.By measuring stemness states of epithelial cells in each tissue type,we revealed that the epithelial cells from newborn forestomach(rumen,reticulum,and omasum)were more transcriptionally indistinct and stochastic compared with the adult stage,which was in contrast to those of abomasum and intestinal tissues.The rapid forestomach development during the early life of calves was driven by epithelial progenitor-like cells with high DNA repair activities and methylation.Moreover,in the forestomach tissues of newborn calves,the Megasphaera genus was involved in regulating the transcriptional plasticity of the epithelial progenitor-like cells by DNA methylation regulation.A novel cell type,the STOML3+cell,was found to be newborn-specific.It apparently plays a crucial role in stemness maintenance of its own and cholangiocytes in the hepatic microenvironment.Our results reveal that the age-and microbiota-dependent cell stemness plasticity drives the postnatal functional maturity of ruminants.展开更多
Background:A rat model for neonatal hypoxic-ischemic brain damage(HIBD)was established to observe the effect of ischemic postconditioning(IPostC)on cerebral edema and the AQP4 expression following HIBD and to verily t...Background:A rat model for neonatal hypoxic-ischemic brain damage(HIBD)was established to observe the effect of ischemic postconditioning(IPostC)on cerebral edema and the AQP4 expression following HIBD and to verily the neuroprotection of IPostC and the relationship between changes of AQP4 expression and cerebral edema.Methods:Water content was measured with dry-wet method,and AQP4 transcription and the protein expression of the lesions were detected with real-time PCR and immunohistochemistry staining,respectively.Results:Within 6-48 hours,the degree of ipsilateral cerebral edema was significantly lower in IPostC-15 s/15 s group than in HIBD group.Similar to the HIBD group,the AQP4 transcription and expression in the IPostC group showed a downward and then upward trend.But the expression was still more evident in the HIBD group than in the IPostC-15 s/15 s group.From 24 to 48 hours,IPostC-15 s/15 s decreased the slowing down expression of AQP4.Conclusion:IPostC has neuroprotective effect on neonatal rats with HIBD and it may relieve cerebral edema by regulating the expression of AQP4.展开更多
An 888-bp full-length ascorbate peroxidase(APX) complementary DNA(cDNA) gene was cloned from Anthurium andraeanum, and designated as AnAPX. It contains a 110-bp 5′-noncoding region, a 28-bp 3′-noncoding region, and ...An 888-bp full-length ascorbate peroxidase(APX) complementary DNA(cDNA) gene was cloned from Anthurium andraeanum, and designated as AnAPX. It contains a 110-bp 5′-noncoding region, a 28-bp 3′-noncoding region, and a 750-bp open reading frame(ORF). This protein is hydrophilic with an aliphatic index of 81.64 and its structure consisting of α-helixes, β-turns, and random coils. The AnAPX protein showed 93%, 87%, 87%, 87%, and 86% similarities to the APX homologs from Zantedeschia aethiopica, Vitis pseudoreticulata, Gossypium hirsutum, Elaeis guineensis, and Zea mays, respectively. AnAPX gene transcript was measured non-significantly in roots, stems, leaves, spathes, and spadices by real-time polymerase chain reaction(RT-PCR) analysis. Interestingly, this gene expression was remarkably up-regulated in response to a cold stress under 6 °C, implying that AnAPX might play an important role in A. andraeanum tolerance to cold stress. To confirm this function we overexpressed AnAPX in tobacco plants by transformation with an AnAPX expression construct driven by CaMV 35S promoter. The transformed tobacco seedlings under 4 °C showed less electrolyte leakage(EL) and malondialdehyde(MDA) content than the control. The content of MDA was correlated with chilling tolerance in these transgenic plants. These results show that AnAPX can prevent the chilling challenged plant from cell membrane damage and ultimately enhance the plant cold tolerance.展开更多
Inorganic photocatalysts have been regarded as a promising candidate in the domain of tumor photodynamic therapy(PDT)due to their inspirational photocatalytic activity.In this study,a Bi_(4)O_(5)Br_(2)photocatalyst wa...Inorganic photocatalysts have been regarded as a promising candidate in the domain of tumor photodynamic therapy(PDT)due to their inspirational photocatalytic activity.In this study,a Bi_(4)O_(5)Br_(2)photocatalyst was synthesized and it exhibited effective photo-killing activity of A549 cells(a human lung carcinoma epithelial cell line)in vitro.On this basis,we modified Bi_(4)O_(5)Br_(2)with carbon quantum dots(CQDs)via a hydrolysis method at room temperature,which resulted in an improved photo-killing effect of Bi_(4)O_(5)Br_(2)to A549 cells.The samples and the interaction between samples and cells were fully characterized.It has been found that the loading of CQDs on Bi_(4)O_(5)Br_(2)can reduce the hydration ratio,increase the cellular uptake and improve the photogenerated reactive oxygen species(ROS)as compared with pristine Bi_(4)O_(5)Br_(2).Electron spin resonance(ESR)analysis and radical-trapping experiments manifested that the ROS contributed to PDT may be·O^(2-)and ·OH.This study may provide a useful strategy to ameliorate the penetrability,cell compatibility and PDT effect upon cancer cells of other inorganic photocatalysts.展开更多
Increasing the efficiency and sustainability of cattle production is an effective way to produce valuable animal proteins for a growing human population.Genetics and nutrition are the 2 major research topics in select...Increasing the efficiency and sustainability of cattle production is an effective way to produce valuable animal proteins for a growing human population.Genetics and nutrition are the 2 major research topics in selecting cattle with beneficial phenotypes and developing genetic potentials for improved performance.There is an inextricable link between genetics and nutrition,which urgently requires researchers to uncover the underlying molecular mechanisms to optimize cattle production.Feedomics integrates a range of omic techniques to reveal the mechanisms at different molecular levels related to animal production and health,which can provide novel insights into the relationships of genes and nutrition/nutrients.In this review,we summarized the applications of feedomics techniques to reveal the effect of genetic elements on the response to nutrition and investigate how nutrients affect the functional genome of cattle from the perspective of both nutrigenetics and nutrigenomics.We highlighted the roles of rumen microbiome in the interactions between host genes and nutrition.Herein,we discuss the importance of feedomics in cattle nutrition research,with a view to ensure that cattle exhibit the best production traits for human consumption from both genetic and nutritional aspects.展开更多
基金the National Natural Science Foundation of China(Nos.42130810,42004065,42074165)the Key Research and Development Program of Hunan Province,China(No.2020SK2058).
基金financially supported by the National Natural Science Foundation of China(No.22008167,21978187,21978196)the Natural Science Foundation for Young Scientists of Shanxi Province,China(Nos.201901D211100,201901D211058,201901D211027)。
基金Project(41574123) supported by the National Natural Science Foundation of ChinaProject(2013FY110800) supported by the National Basic Research Scientific Program of China
基金Projects(21676178,21506144,21706179)supported by the National Natural Science Foundation of ChinaProject(2019L0138)supported by the Science and Technology Innovation Program of Higher Education Institutions in Shanxi Province,ChinaProject(201901D211100)supported by the Natural Science Foundation of Shanxi Province for Young Scientists,China
基金financially supported by the National Natural Science Foundation of China(Nos.41974049,42074165)the Science and Technology on Parallel and Distributed Processing Laboratory,China(No.6142110180202)。
基金the National Natural Science Foundation of China(Nos.42004107,42074165)the Open Research Fund Program of Key Laboratory of Metallogenic Prediction of Nonferrous Metals and Geological Environment Monitoring(Central South University)+1 种基金Ministry of Education,China(No.2019YSJS13)Department of Water Resources of Hunan Province,China(No.XSKJ2019081).
基金Supported by Project Funding of the Scientific Research Foundation of Traditional Chinese Medicine of Fujian Provincial Health and Family Planning Commission,No.2017FJZYZY203the Training of Young and Middle-Aged Backbone Personnel of Fujian Provincial Health and Family Planning Commission,No.2016-ZQN-67/
文摘BACKGROUND Qingjie Fuzheng granules(QFGs) are part of a traditional Chinese medicine formula, which has been widely used and found to be clinically effective with few side effects in various cancer treatments, including colorectal cancer(CRC).However, the precise mechanisms and molecular signaling pathways involved in the activity of QFGs' anticancer effect have not been reported in the literature. In this study, we hypothesized that QFGs can inhibit the growth of colorectal cancer cells, and that its mechanism is closely related to one or more intracellular signal transduction pathways.AIM To better evaluate the mechanism underlying the anti-cancer effect of QFGs on the CRC cell lines HCT-116 and HCT-8.METHOD First, we measured cell viability and cytotoxicity by performing MTT and lactate dehydrogenase(LDH) assays. We evaluated the role of QFGs in cell proliferation and apoptosis by assessing colony formation and analyzing Hoechst 33258 staining. Second, cell cycle and apoptosis rates were measured by fluorescence activated cell sorting, and the expression levels of survivin, cyclin D1, CDK4, p21,Bax, Bcl-2, Fas, FasL, and cleaved-caspase-3/-8/-9 were measured by performing western blots and caspase activity assays. Furthermore, inhibitors of caspase-3/-8/-9 were used to elucidate the specific apoptosis pathway induced by QFGs in cancer cells. Finally, activation of the PI3 K/AKT and ERK signaling pathwayswas examined using the western blot assay to investigate the possible mechanism.RESULTS MTT and LDH assays revealed that after 0.5-2.0 mg/mL of QFGs treatment, cell viability was reduced by(6.90% ± 1.03%)–(59.70% ± 1.51%)(HCT-116; P < 0.05)and(5.56% ± 4.52%)–(49.44% ± 2.47%)(HCT-8; P < 0.05), and cytotoxicity was increased from 0.52 ± 0.023 to 0.77 ± 0.002(HCT-116; P < 0.01) and from 0.56 ±0.054 to 0.81 ± 0.044(HCT-8; P < 0.01) compared with the non-QFGs treatment groups. Additionally, colony formation and Hoechst 33258 staining assays showed that QFGs inhibited proliferation and induced apoptosis in CRC cells.QFGs also increased the expression levels of Bax, Fas and FasL, decreased the level of Bcl-2, and stimulated the activation of caspase-3/-8/-9, which were revealed by western blot and caspase activity assays. In contrast, when adding the three caspase inhibitors, the suppression effect of QFGs on cell viability and apoptosis were markedly inhibited. Moreover, QFGs suppressed the phosphorylation levels of PI3 K, AKT and ERK.CONCLUSION These results demonstrated that QFGs can inhibit CRC cell proliferation and induce apoptosis by suppressing the PI3 K/AKT and ERK signaling pathways.
基金the National Key R&D Program Youth Project(2022YFD1301700)the Natural Science Foundation of Zhejiang Province Out standing Youth Fund Project(LR23C170001)+2 种基金the National Natural Science Foundation of China(32002207,Beijing)the China Agriculture(Dairy)Research System(CARS-36,Beijing)the“Hundred Talents Program”Research Professor Start-up Fund of Zhejiang University.
文摘Newborn ruminants are considered functionally monogastric animals.The poor understanding of cellular differences between newborn and mature ruminants prevents the improvement of health and performance of domestic ruminants.Here,we performed the single-cell RNA sequencing on the rumen,reticulum,omasum,abomasum,duodenum,jejunum,ileum,cecum,colon,rectum,liver,salivary gland,and mammary gland from newborn and adult cattle.A comprehensive single-cell transcriptomic atlas covering 235,941 high-quality single cells and 78 cell types was deciphered.A Cattle Cell Landscape database(http://cattlecelllandscape.zju.edu.cn)was established to elaborately display the data and facilitate effective annotation of cattle cell types and subtypes for the broad research community.By measuring stemness states of epithelial cells in each tissue type,we revealed that the epithelial cells from newborn forestomach(rumen,reticulum,and omasum)were more transcriptionally indistinct and stochastic compared with the adult stage,which was in contrast to those of abomasum and intestinal tissues.The rapid forestomach development during the early life of calves was driven by epithelial progenitor-like cells with high DNA repair activities and methylation.Moreover,in the forestomach tissues of newborn calves,the Megasphaera genus was involved in regulating the transcriptional plasticity of the epithelial progenitor-like cells by DNA methylation regulation.A novel cell type,the STOML3+cell,was found to be newborn-specific.It apparently plays a crucial role in stemness maintenance of its own and cholangiocytes in the hepatic microenvironment.Our results reveal that the age-and microbiota-dependent cell stemness plasticity drives the postnatal functional maturity of ruminants.
基金supported by a grant from the National Natural Science Foundation of China(810705390)
文摘Background:A rat model for neonatal hypoxic-ischemic brain damage(HIBD)was established to observe the effect of ischemic postconditioning(IPostC)on cerebral edema and the AQP4 expression following HIBD and to verily the neuroprotection of IPostC and the relationship between changes of AQP4 expression and cerebral edema.Methods:Water content was measured with dry-wet method,and AQP4 transcription and the protein expression of the lesions were detected with real-time PCR and immunohistochemistry staining,respectively.Results:Within 6-48 hours,the degree of ipsilateral cerebral edema was significantly lower in IPostC-15 s/15 s group than in HIBD group.Similar to the HIBD group,the AQP4 transcription and expression in the IPostC group showed a downward and then upward trend.But the expression was still more evident in the HIBD group than in the IPostC-15 s/15 s group.From 24 to 48 hours,IPostC-15 s/15 s decreased the slowing down expression of AQP4.Conclusion:IPostC has neuroprotective effect on neonatal rats with HIBD and it may relieve cerebral edema by regulating the expression of AQP4.
基金supported by the Science and Technology Key Project ofZhejiang Province(No.2009C12095)the National NaturalScience Foundation of China(No.31200527)
文摘An 888-bp full-length ascorbate peroxidase(APX) complementary DNA(cDNA) gene was cloned from Anthurium andraeanum, and designated as AnAPX. It contains a 110-bp 5′-noncoding region, a 28-bp 3′-noncoding region, and a 750-bp open reading frame(ORF). This protein is hydrophilic with an aliphatic index of 81.64 and its structure consisting of α-helixes, β-turns, and random coils. The AnAPX protein showed 93%, 87%, 87%, 87%, and 86% similarities to the APX homologs from Zantedeschia aethiopica, Vitis pseudoreticulata, Gossypium hirsutum, Elaeis guineensis, and Zea mays, respectively. AnAPX gene transcript was measured non-significantly in roots, stems, leaves, spathes, and spadices by real-time polymerase chain reaction(RT-PCR) analysis. Interestingly, this gene expression was remarkably up-regulated in response to a cold stress under 6 °C, implying that AnAPX might play an important role in A. andraeanum tolerance to cold stress. To confirm this function we overexpressed AnAPX in tobacco plants by transformation with an AnAPX expression construct driven by CaMV 35S promoter. The transformed tobacco seedlings under 4 °C showed less electrolyte leakage(EL) and malondialdehyde(MDA) content than the control. The content of MDA was correlated with chilling tolerance in these transgenic plants. These results show that AnAPX can prevent the chilling challenged plant from cell membrane damage and ultimately enhance the plant cold tolerance.
基金This research was financially supported by the National Natural Science Foundation of China(Nos.21303116,21676178 and 21706179).
文摘Inorganic photocatalysts have been regarded as a promising candidate in the domain of tumor photodynamic therapy(PDT)due to their inspirational photocatalytic activity.In this study,a Bi_(4)O_(5)Br_(2)photocatalyst was synthesized and it exhibited effective photo-killing activity of A549 cells(a human lung carcinoma epithelial cell line)in vitro.On this basis,we modified Bi_(4)O_(5)Br_(2)with carbon quantum dots(CQDs)via a hydrolysis method at room temperature,which resulted in an improved photo-killing effect of Bi_(4)O_(5)Br_(2)to A549 cells.The samples and the interaction between samples and cells were fully characterized.It has been found that the loading of CQDs on Bi_(4)O_(5)Br_(2)can reduce the hydration ratio,increase the cellular uptake and improve the photogenerated reactive oxygen species(ROS)as compared with pristine Bi_(4)O_(5)Br_(2).Electron spin resonance(ESR)analysis and radical-trapping experiments manifested that the ROS contributed to PDT may be·O^(2-)and ·OH.This study may provide a useful strategy to ameliorate the penetrability,cell compatibility and PDT effect upon cancer cells of other inorganic photocatalysts.
基金supported by the Fundamental Research Funds for the Central Universities(No.2011XZZX006)the National Natural Science Foundation of China(No.31172229)the University of Alberta Research Internship Program Summer 2012,Canada
基金the grants from the National Natural Science Foundation of China(32002207)the Fundamental Research Funds for the Zhejiang Provincial Universities(2021XZZX027)the“Hundred Talents Program”Research Professor Start-up Fund of Zhejiang University.
文摘Increasing the efficiency and sustainability of cattle production is an effective way to produce valuable animal proteins for a growing human population.Genetics and nutrition are the 2 major research topics in selecting cattle with beneficial phenotypes and developing genetic potentials for improved performance.There is an inextricable link between genetics and nutrition,which urgently requires researchers to uncover the underlying molecular mechanisms to optimize cattle production.Feedomics integrates a range of omic techniques to reveal the mechanisms at different molecular levels related to animal production and health,which can provide novel insights into the relationships of genes and nutrition/nutrients.In this review,we summarized the applications of feedomics techniques to reveal the effect of genetic elements on the response to nutrition and investigate how nutrients affect the functional genome of cattle from the perspective of both nutrigenetics and nutrigenomics.We highlighted the roles of rumen microbiome in the interactions between host genes and nutrition.Herein,we discuss the importance of feedomics in cattle nutrition research,with a view to ensure that cattle exhibit the best production traits for human consumption from both genetic and nutritional aspects.
基金Project supported by the Zhejiang Provincial Key Science and Technology Innovation Team(No.2011R50025)the National Natural Science Foundation of China(No.31328022)
