Objective:As a member of the peptidyl arginine deiminase(PAD)family,PADI3 is weakly expressed in colon cancer tissues and highly expressed in adjacent colon cancer tissues.However,the role of PADI3 in colon cancer is ...Objective:As a member of the peptidyl arginine deiminase(PAD)family,PADI3 is weakly expressed in colon cancer tissues and highly expressed in adjacent colon cancer tissues.However,the role of PADI3 in colon cancer is unclear.In this study,we investigated the function and molecular mechanism of PADI3 in colon cancer tumorigenesis.Methods:Western blot and real-time PCR were used to detect the expression levels of several genes.CCK-8,flow cytometry(FCM)and colony formation assays were used to examine cell proliferation,the cell cycle and colony formation ability.RNAsequencing analysis was used to study the molecular mechanism of PADI3 in tumorigenesis.A truncation mutation experiment was performed to determine the key functional domain of PADI3.Results:PADI3 overexpression inhibited cell proliferation and colony formation and led to G1 phase arrest in both HCT116(originating from primary colon cancer)and LoVo(originating from metastatic tumor nodules of colon cancer)cells.PADI3-expressing HCT116 cells had a lower tumor formation rate and produced smaller tumors than control cells.PADI3 significantly decreased Sirtuin2(Sirt2)and Snail expression and AKT phosphorylation and increased p21 expression,and Sirt2 overexpression partly reversed the effects induced by PADI3 overexpression.Immunocytochemistry showed that PADI3 is mainly localized in the cytoplasm.Truncation mutation experiments showed that the C-domain is the key domain involved in the antitumor activity of PADI3.Conclusions:PADI3 suppresses Snail expression and AKT phosphorylation and promotes p21 expression by downregulating Sirt2 expression in the cytoplasm,and the C-domain is the key domain for its antitumor activity.展开更多
Sitobion avenae(F.) and Rhopalosiphum padi(L.) are two important pests of wheat in China.They typically coexist in fields during the late period of wheat growth.Sulfoxaflor is a novel sulfoximine insecticide that demo...Sitobion avenae(F.) and Rhopalosiphum padi(L.) are two important pests of wheat in China.They typically coexist in fields during the late period of wheat growth.Sulfoxaflor is a novel sulfoximine insecticide that demonstrates broad-spectrum efficacy,especially in targeting sap-feeding insects.This study was carried out to investigate the sublethal effects of sulfoxaflor on the development,longevity,and reproduction of two species of wheat aphids.Our results showed that sublethal concentrations of sulfoxaflor did not cause significant effects on the fecundity or the longevity of the parent generation(F0 generation) of either S.avenae or R.padi.However,it caused transgenerational sublethal effects.For S.avenae,adult longevity of F1 generation was significantly decreased.No significant differences were observed on the population parameters of S.avenae in the F1 generation.For R.padi,the adult preoviposition period(APOP) and the total preoviposition period(TPOP) of F1 generation were significantly reduced.The mean generation time(T) was significantly reduced in the R.padi F1 generation.What’s more,the intrinsic rate of increase(rm) and the finite rate of increase(λ) were significantly increased in the R.padi F1 generation.Taken together,these results suggest that exposure to the LC25 of sulfoxafl had no effects on the parent generation of S.avenae or R.padi,but it reduced adult longevity of S.avenae as a negative effect and increased the rm and λ of R.padi in the first progeny generation,which may have an impact on the population dynamics of R.padi.展开更多
Objective： The aim of the research was to study peptidylarginine deiminase type 4 （PAD4/PADI4） expression and its tumodgenic mechanism in hepatocellular carcinomas. Methods： Expressions of PADI4 and p53 were inves...Objective： The aim of the research was to study peptidylarginine deiminase type 4 （PAD4/PADI4） expression and its tumodgenic mechanism in hepatocellular carcinomas. Methods： Expressions of PADI4 and p53 were investigated in tumors and non-tumor tissues by Western blot in patients with hepatocellular carcinomas. We constructed plasmid of PADI4-Flag and transfected it in Hela cells to investigate the mechanism. Results： Western blot analysis showed higher PADI4 expression in hepatocellular carcinomas than in the surrounding healthy tissues. Furthermore, by Western blot, we detected decreased p53 levels in the tumor tissues of patients with hepatocellular carcinomas compared to surrounding healthy tissues. In Hela cells transfected with PcDNA3.0-Flag-PADI4 plasmid, the expression of p53 decreased obviously. Conclusion： Our results suggest that PADI4 elevated in the tissues of hepatocellular carcinomas and induced tumorigenic by down-regulating p53 expression.展开更多
The biochemical mechanism of resistance of 9 Aegilops species including A.biuncialis,A.juvenalis, A.ovata, A.kotschyi var. varianilis, A.triaristata, A.tauschii, A.vavilovii, A.crassa and A.ventricosa ...The biochemical mechanism of resistance of 9 Aegilops species including A.biuncialis,A.juvenalis, A.ovata, A.kotschyi var. varianilis, A.triaristata, A.tauschii, A.vavilovii, A.crassa and A.ventricosa in Triticeae to oat bird cherry aphid ( Rhopalosiphum padi ) were reported for the first time. The results showed that the content of total phenols in seedling was not associated with resistance to this aphid. The level of DIMBOA was negatively related to intrinsic innate rate of increase ( r m ) of R. padi. Neither of soluable sugar nor total phenols in adult stage was associated with resistance level. However, concentrations of free proline and serine in leaf were positively related to r m of R. padi ( r m =0.0636+0.23x pro ** +1.982x ser *). The content of DIMBOA was high negatively related to r m of R. padi ( r =0.819 ** ). The low level of free proline and serine and high concentration of DIMBOA could be regarded as important elements for resistance of Aegilops species to R. padi.展开更多
The phytochemical study of Uruguayan specimens of Allophylus edulis (Sapindaceae) yielded the isolation of various natural products being some of them reported for the first time in this species. Although most of them...The phytochemical study of Uruguayan specimens of Allophylus edulis (Sapindaceae) yielded the isolation of various natural products being some of them reported for the first time in this species. Although most of them are ubiquitous in the plant kingdom, some revealed in this study to have anti insect properties. Two sesquiterpenes (6,7-Epoxicaryophyllene and spathulenol), two phytosterols (sitosterone and sitosterol), a pentacyclic triterpene (lupeol) and a clerodane diterpene were isolated. 6,7-Epoxycaryophyllene, lupeol and sitosterol showed to be deterrent against the aphid Myzus persicae and the coleopteran Epilachna paenulata. Moreover, the crude ethanolic extract of twigs of A. edulis showed to be deterrent against both insect species being some of its fractions also active against another aphid, Rhopalosiphum padi. Various active compounds against different insect models have been isolated from the twigs extract of A. edulis. The results evidenced synergic as well as antagonistic effects in the mixture, summed to differential activity against the insects, a desirable attribute when developing botanical pesticides.展开更多
Tumor relapse and metastasis are the major causes of mortality associated with urothelial cancer.In the tumor microenvironment,negative regulatory molecules and various immune cell subtypes suppress antitumor immunity...Tumor relapse and metastasis are the major causes of mortality associated with urothelial cancer.In the tumor microenvironment,negative regulatory molecules and various immune cell subtypes suppress antitumor immunity.The inflammatory microenvironment,associated with neutrophils and neutrophil extracellular traps(NETs),promotes tumor metastasis.However,no drugs are currently available to specifically inhibit neutrophils and NETs.In this study,we first demonstrated that icaritin(ICT),a Chinese herbal remedy that is a first-line treatment for advanced and incurable hepatocellular carcinoma,reduces NETs caused by suicidal NETosis and prevents neutrophil infiltration in the tumor microenvironment.Mechanistically,ICT binds to and inhibits the expression of PADI2 in neutrophils,thereby suppressing PADI2-mediated histone citrullination.Moreover,ICT inhibits ROS generation,suppresses the MAPK signaling pathway,and inhibits NET-induced tumor metastasis.Simultaneously,ICT inhibits tumoral PADI2-mediated histone citrullination,which consequently suppresses the transcription of neutrophil-recruiting genes such as GM-CSF and IL-6.The downregulation of IL-6 expression,in turn,forms a regulatory feedback loop through the JAK2/STAT3/IL-6 axis.Through a retrospective study of clinical samples,we found a correlation between neutrophils,NETs,UCa prognosis,and immune evasion.Combining ICT with immune checkpoint inhibitors may have synergistic effects.In summary,our study demonstrated that ICT could be a novel inhibitor of NETs and a novel UCa treatment.展开更多
基金supported by the National Natural Science Foundation for the Youth of China (Grant No. 81802422 and 81702440)the Shandong Provincial Key R & D Program (Nos. 2019GSF108115, 2017GSF218102)+2 种基金Jinan Science and Technology Development Program (Nos. 201907116)Shandong Science and Technology Development Plan (Grant No. 2017GFS18195)Shandong Traditional Chinese Medicine Science and Technology Development Programs (Grant No. 2017-173)
文摘Objective:As a member of the peptidyl arginine deiminase(PAD)family,PADI3 is weakly expressed in colon cancer tissues and highly expressed in adjacent colon cancer tissues.However,the role of PADI3 in colon cancer is unclear.In this study,we investigated the function and molecular mechanism of PADI3 in colon cancer tumorigenesis.Methods:Western blot and real-time PCR were used to detect the expression levels of several genes.CCK-8,flow cytometry(FCM)and colony formation assays were used to examine cell proliferation,the cell cycle and colony formation ability.RNAsequencing analysis was used to study the molecular mechanism of PADI3 in tumorigenesis.A truncation mutation experiment was performed to determine the key functional domain of PADI3.Results:PADI3 overexpression inhibited cell proliferation and colony formation and led to G1 phase arrest in both HCT116(originating from primary colon cancer)and LoVo(originating from metastatic tumor nodules of colon cancer)cells.PADI3-expressing HCT116 cells had a lower tumor formation rate and produced smaller tumors than control cells.PADI3 significantly decreased Sirtuin2(Sirt2)and Snail expression and AKT phosphorylation and increased p21 expression,and Sirt2 overexpression partly reversed the effects induced by PADI3 overexpression.Immunocytochemistry showed that PADI3 is mainly localized in the cytoplasm.Truncation mutation experiments showed that the C-domain is the key domain involved in the antitumor activity of PADI3.Conclusions:PADI3 suppresses Snail expression and AKT phosphorylation and promotes p21 expression by downregulating Sirt2 expression in the cytoplasm,and the C-domain is the key domain for its antitumor activity.
基金supported by the National Barley Industry Technology System of China(CARS-05)
文摘Sitobion avenae(F.) and Rhopalosiphum padi(L.) are two important pests of wheat in China.They typically coexist in fields during the late period of wheat growth.Sulfoxaflor is a novel sulfoximine insecticide that demonstrates broad-spectrum efficacy,especially in targeting sap-feeding insects.This study was carried out to investigate the sublethal effects of sulfoxaflor on the development,longevity,and reproduction of two species of wheat aphids.Our results showed that sublethal concentrations of sulfoxaflor did not cause significant effects on the fecundity or the longevity of the parent generation(F0 generation) of either S.avenae or R.padi.However,it caused transgenerational sublethal effects.For S.avenae,adult longevity of F1 generation was significantly decreased.No significant differences were observed on the population parameters of S.avenae in the F1 generation.For R.padi,the adult preoviposition period(APOP) and the total preoviposition period(TPOP) of F1 generation were significantly reduced.The mean generation time(T) was significantly reduced in the R.padi F1 generation.What’s more,the intrinsic rate of increase(rm) and the finite rate of increase(λ) were significantly increased in the R.padi F1 generation.Taken together,these results suggest that exposure to the LC25 of sulfoxafl had no effects on the parent generation of S.avenae or R.padi,but it reduced adult longevity of S.avenae as a negative effect and increased the rm and λ of R.padi in the first progeny generation,which may have an impact on the population dynamics of R.padi.
文摘Objective： The aim of the research was to study peptidylarginine deiminase type 4 （PAD4/PADI4） expression and its tumodgenic mechanism in hepatocellular carcinomas. Methods： Expressions of PADI4 and p53 were investigated in tumors and non-tumor tissues by Western blot in patients with hepatocellular carcinomas. We constructed plasmid of PADI4-Flag and transfected it in Hela cells to investigate the mechanism. Results： Western blot analysis showed higher PADI4 expression in hepatocellular carcinomas than in the surrounding healthy tissues. Furthermore, by Western blot, we detected decreased p53 levels in the tumor tissues of patients with hepatocellular carcinomas compared to surrounding healthy tissues. In Hela cells transfected with PcDNA3.0-Flag-PADI4 plasmid, the expression of p53 decreased obviously. Conclusion： Our results suggest that PADI4 elevated in the tissues of hepatocellular carcinomas and induced tumorigenic by down-regulating p53 expression.
文摘The biochemical mechanism of resistance of 9 Aegilops species including A.biuncialis,A.juvenalis, A.ovata, A.kotschyi var. varianilis, A.triaristata, A.tauschii, A.vavilovii, A.crassa and A.ventricosa in Triticeae to oat bird cherry aphid ( Rhopalosiphum padi ) were reported for the first time. The results showed that the content of total phenols in seedling was not associated with resistance to this aphid. The level of DIMBOA was negatively related to intrinsic innate rate of increase ( r m ) of R. padi. Neither of soluable sugar nor total phenols in adult stage was associated with resistance level. However, concentrations of free proline and serine in leaf were positively related to r m of R. padi ( r m =0.0636+0.23x pro ** +1.982x ser *). The content of DIMBOA was high negatively related to r m of R. padi ( r =0.819 ** ). The low level of free proline and serine and high concentration of DIMBOA could be regarded as important elements for resistance of Aegilops species to R. padi.
文摘The phytochemical study of Uruguayan specimens of Allophylus edulis (Sapindaceae) yielded the isolation of various natural products being some of them reported for the first time in this species. Although most of them are ubiquitous in the plant kingdom, some revealed in this study to have anti insect properties. Two sesquiterpenes (6,7-Epoxicaryophyllene and spathulenol), two phytosterols (sitosterone and sitosterol), a pentacyclic triterpene (lupeol) and a clerodane diterpene were isolated. 6,7-Epoxycaryophyllene, lupeol and sitosterol showed to be deterrent against the aphid Myzus persicae and the coleopteran Epilachna paenulata. Moreover, the crude ethanolic extract of twigs of A. edulis showed to be deterrent against both insect species being some of its fractions also active against another aphid, Rhopalosiphum padi. Various active compounds against different insect models have been isolated from the twigs extract of A. edulis. The results evidenced synergic as well as antagonistic effects in the mixture, summed to differential activity against the insects, a desirable attribute when developing botanical pesticides.
基金grants from National Natural Science Foundation of China(No.82373222,No.82202970)Leading Talent Program by Shanghai Municipal Health Commission(2022LJ008,China)+1 种基金Shanghai Shenkang Hospital Development Center(SHDC12021104,China)Science and Technology Commission of Shanghai Municipality(22Y21900200&22YF1404300,China).
文摘Tumor relapse and metastasis are the major causes of mortality associated with urothelial cancer.In the tumor microenvironment,negative regulatory molecules and various immune cell subtypes suppress antitumor immunity.The inflammatory microenvironment,associated with neutrophils and neutrophil extracellular traps(NETs),promotes tumor metastasis.However,no drugs are currently available to specifically inhibit neutrophils and NETs.In this study,we first demonstrated that icaritin(ICT),a Chinese herbal remedy that is a first-line treatment for advanced and incurable hepatocellular carcinoma,reduces NETs caused by suicidal NETosis and prevents neutrophil infiltration in the tumor microenvironment.Mechanistically,ICT binds to and inhibits the expression of PADI2 in neutrophils,thereby suppressing PADI2-mediated histone citrullination.Moreover,ICT inhibits ROS generation,suppresses the MAPK signaling pathway,and inhibits NET-induced tumor metastasis.Simultaneously,ICT inhibits tumoral PADI2-mediated histone citrullination,which consequently suppresses the transcription of neutrophil-recruiting genes such as GM-CSF and IL-6.The downregulation of IL-6 expression,in turn,forms a regulatory feedback loop through the JAK2/STAT3/IL-6 axis.Through a retrospective study of clinical samples,we found a correlation between neutrophils,NETs,UCa prognosis,and immune evasion.Combining ICT with immune checkpoint inhibitors may have synergistic effects.In summary,our study demonstrated that ICT could be a novel inhibitor of NETs and a novel UCa treatment.
