CDGSH iron sulfur domain 2 can inhibit ferroptosis,which has been associated with cerebral ischemia/reperfusion,in individuals with head and neck cancer.Therefore,CDGSH iron sulfur domain 2 may be implicated in cerebr...CDGSH iron sulfur domain 2 can inhibit ferroptosis,which has been associated with cerebral ischemia/reperfusion,in individuals with head and neck cancer.Therefore,CDGSH iron sulfur domain 2 may be implicated in cerebral ischemia/reperfusion injury.To validate this hypothesis in the present study,we established mouse models of occlusion of the middle cerebral artery and HT22 cell models of oxygen-glucose deprivation and reoxygenation to mimic cerebral ischemia/reperfusion injury in vivo and in vitro,respectively.We found remarkably decreased CDGSH iron sulfur domain 2 expression in the mouse brain tissue and HT22 cells.When we used adeno-associated virus and plasmid to up-regulate CDGSH iron sulfur domain 2 expression in the brain tissue and HT22 cell models separately,mouse neurological dysfunction was greatly improved;the cerebral infarct volume was reduced;the survival rate of HT22 cells was increased;HT22 cell injury was alleviated;the expression of ferroptosis-related glutathione peroxidase 4,cystine-glutamate antiporter,and glutathione was increased;the levels of malondialdehyde,iron ions,and the expression of transferrin receptor 1 were decreased;and the expression of nuclear-factor E2-related factor 2/heme oxygenase 1 was increased.Inhibition of CDGSH iron sulfur domain 2 upregulation via the nuclear-factor E2-related factor 2 inhibitor ML385 in oxygen-glucose deprived and reoxygenated HT22 cells blocked the neuroprotective effects of CDGSH iron sulfur domain 2 up-regulation and the activation of the nuclear-factor E2-related factor 2/heme oxygenase 1 pathway.Our data indicate that the up-regulation of CDGSH iron sulfur domain 2 can attenuate cerebral ischemia/reperfusion injury,thus providing theoretical support from the perspectives of cytology and experimental zoology for the use of this protein as a therapeutic target in patients with cerebral ischemia/reperfusion injury.展开更多
Objective:To evaluate the effect of erianin on the viability,migration,and invasion of KB cells and elucidate its underlying mechanisms.Methods:Cell Counting Kit-8,colony formation,wound healing,and Transwell assays w...Objective:To evaluate the effect of erianin on the viability,migration,and invasion of KB cells and elucidate its underlying mechanisms.Methods:Cell Counting Kit-8,colony formation,wound healing,and Transwell assays were used to determine the proliferation,migration,and invasion of oral cancer KB cells.Furthermore,malondialdehyde(MDA)and glutathione(GSH)levels were determined.Fluorescent probes were used to detect changes in intracellular reactive oxygen species and iron ions.Additionally,the expressions of ferroptosis-related proteins,NF-E2-related factor 2(Nrf2),ferritin heavy chain 1(FTH1),heme oxygenase 1(HO-1),and glutathione peroxidase 4(GPX4)were analyzed by Western blotting assays.Results:Erianin induced ferroptosis and inhibited the proliferation,migration,and invasion of KB cells.Moreover,erianin decreased GSH level,increased MDA level,elevated intracellular ROS and Fe2+contents,and downregulated the expression of the ferroptosis-related proteins Nrf2,HO-1,GPX4,and FTH1 in KB cells.These effects of erianin were effectively reversed by a ferroptosis inhibitor,ferrostatin-1.Conclusions:Erianin inhibits the proliferation,migration,and invasion of oral cancer cells and induces ferroptosis via the Nrf2/HO-1/GPX4 signaling pathway.Therefore,erianin may be a potential candidate for the treatment of oral cancer.展开更多
To achieve highly selective synergistic chemotherapy attractive for clinical translation,the precise polymeric nano-prodrugs(PPD-NPs)were successfully constructed via the facile crosslinking reaction between p H-sensi...To achieve highly selective synergistic chemotherapy attractive for clinical translation,the precise polymeric nano-prodrugs(PPD-NPs)were successfully constructed via the facile crosslinking reaction between p H-sensitive poly(ortho ester)s and reduction-sensitive small molecule synergistic prodrug(Pt(IV)-1).PPD-NPs endowed the defined structure and high drug loading of cisplatin and demethylcantharidin(DMC).Moreover,PPD-NPs exhibited steady long-term storage and circulation via the crosslinked structure,suitable negative potentials and low critical micelle concentration(CMC),improved selective tumour accumulation and cellular internalization via dynamic size transition and surficial amino protonation at tumoural extracellular p H,promoted efficient disintegration and drug release at tumoural intracellular p H/glutathione,and enhanced cytotoxicity via the synergistic effect between cisplatin and DMC with the feed ratio of 1:2,achieving significant tumour suppression while decreasing the side effects.Thus,the dynamic crosslinked polymeric nano-prodrugs exhibit tremendous potential for clinically targeted synergistic cancer therapy.展开更多
Coordination-driven self-assembly strategy has demonstrated the efficiency and versatility to construct well-ordered supramolecular coordination complexes(SCCs) such as discrete metallacycles and metallacages. In rece...Coordination-driven self-assembly strategy has demonstrated the efficiency and versatility to construct well-ordered supramolecular coordination complexes(SCCs) such as discrete metallacycles and metallacages. In recent years, it has aroused tremendous interest to build more complexed self-assembled structures via the implementation of additional non-covalent recognition motifs on the SCCs platform. In this work, we have successfully attained this objective, with the elaborate manipulation of non-interfering pyridine-Pt^(2+) and molecular tweezer/guest complexation in a hierarchical self-assembly manner. The resulting SCCs-based linear supramolecular polymers exhibit intriguing NIR-emissive behaviors, primarily attributed to the presence of intermolecular Pt(Ⅱ)-Pt(Ⅱ) metal-metal interactions in the non-covalent tweezering structure. Hence, supramolecular engineering of multiple non-covalent interactions offers a feasible avenue toward functional materials with tailored properties.展开更多
基金supported by the National Natural Science Foundation of China,No.81402930Natural Science Foundation of Universities in Anhui Province,No.KJ2021A0688+2 种基金National College Students Innovation and Entrepreneurship Program,No.202110367071Key projects of science and technology projects of Bengbu Medical College,No.2020byzd017512 Talents Training Program of Bengbu Medical College,No.BY51201104(all to SYD).
文摘CDGSH iron sulfur domain 2 can inhibit ferroptosis,which has been associated with cerebral ischemia/reperfusion,in individuals with head and neck cancer.Therefore,CDGSH iron sulfur domain 2 may be implicated in cerebral ischemia/reperfusion injury.To validate this hypothesis in the present study,we established mouse models of occlusion of the middle cerebral artery and HT22 cell models of oxygen-glucose deprivation and reoxygenation to mimic cerebral ischemia/reperfusion injury in vivo and in vitro,respectively.We found remarkably decreased CDGSH iron sulfur domain 2 expression in the mouse brain tissue and HT22 cells.When we used adeno-associated virus and plasmid to up-regulate CDGSH iron sulfur domain 2 expression in the brain tissue and HT22 cell models separately,mouse neurological dysfunction was greatly improved;the cerebral infarct volume was reduced;the survival rate of HT22 cells was increased;HT22 cell injury was alleviated;the expression of ferroptosis-related glutathione peroxidase 4,cystine-glutamate antiporter,and glutathione was increased;the levels of malondialdehyde,iron ions,and the expression of transferrin receptor 1 were decreased;and the expression of nuclear-factor E2-related factor 2/heme oxygenase 1 was increased.Inhibition of CDGSH iron sulfur domain 2 upregulation via the nuclear-factor E2-related factor 2 inhibitor ML385 in oxygen-glucose deprived and reoxygenated HT22 cells blocked the neuroprotective effects of CDGSH iron sulfur domain 2 up-regulation and the activation of the nuclear-factor E2-related factor 2/heme oxygenase 1 pathway.Our data indicate that the up-regulation of CDGSH iron sulfur domain 2 can attenuate cerebral ischemia/reperfusion injury,thus providing theoretical support from the perspectives of cytology and experimental zoology for the use of this protein as a therapeutic target in patients with cerebral ischemia/reperfusion injury.
文摘Objective:To evaluate the effect of erianin on the viability,migration,and invasion of KB cells and elucidate its underlying mechanisms.Methods:Cell Counting Kit-8,colony formation,wound healing,and Transwell assays were used to determine the proliferation,migration,and invasion of oral cancer KB cells.Furthermore,malondialdehyde(MDA)and glutathione(GSH)levels were determined.Fluorescent probes were used to detect changes in intracellular reactive oxygen species and iron ions.Additionally,the expressions of ferroptosis-related proteins,NF-E2-related factor 2(Nrf2),ferritin heavy chain 1(FTH1),heme oxygenase 1(HO-1),and glutathione peroxidase 4(GPX4)were analyzed by Western blotting assays.Results:Erianin induced ferroptosis and inhibited the proliferation,migration,and invasion of KB cells.Moreover,erianin decreased GSH level,increased MDA level,elevated intracellular ROS and Fe2+contents,and downregulated the expression of the ferroptosis-related proteins Nrf2,HO-1,GPX4,and FTH1 in KB cells.These effects of erianin were effectively reversed by a ferroptosis inhibitor,ferrostatin-1.Conclusions:Erianin inhibits the proliferation,migration,and invasion of oral cancer cells and induces ferroptosis via the Nrf2/HO-1/GPX4 signaling pathway.Therefore,erianin may be a potential candidate for the treatment of oral cancer.
基金supported by the Anhui Engineering Technology Research center of Biochemical Pharmaceutical(Bengbu Medical College)the National Natural Science Foundation of China(No.51803001)the Research Foundation of Education Department of Anhui Province of China(No.KJ2018ZD003,KJ2018A0006 and KJ2019A0015)the Academic and Technology Introduction Project of Anhui University(AU02303203)。
文摘To achieve highly selective synergistic chemotherapy attractive for clinical translation,the precise polymeric nano-prodrugs(PPD-NPs)were successfully constructed via the facile crosslinking reaction between p H-sensitive poly(ortho ester)s and reduction-sensitive small molecule synergistic prodrug(Pt(IV)-1).PPD-NPs endowed the defined structure and high drug loading of cisplatin and demethylcantharidin(DMC).Moreover,PPD-NPs exhibited steady long-term storage and circulation via the crosslinked structure,suitable negative potentials and low critical micelle concentration(CMC),improved selective tumour accumulation and cellular internalization via dynamic size transition and surficial amino protonation at tumoural extracellular p H,promoted efficient disintegration and drug release at tumoural intracellular p H/glutathione,and enhanced cytotoxicity via the synergistic effect between cisplatin and DMC with the feed ratio of 1:2,achieving significant tumour suppression while decreasing the side effects.Thus,the dynamic crosslinked polymeric nano-prodrugs exhibit tremendous potential for clinically targeted synergistic cancer therapy.
基金financially supported by the National Natural Science Foundation of China(No.21674106)the Fundamental Research Funds for the Central Universities(No.WK3450000001)CAS Youth Innovation Promotion Association(No.2015365)
文摘Coordination-driven self-assembly strategy has demonstrated the efficiency and versatility to construct well-ordered supramolecular coordination complexes(SCCs) such as discrete metallacycles and metallacages. In recent years, it has aroused tremendous interest to build more complexed self-assembled structures via the implementation of additional non-covalent recognition motifs on the SCCs platform. In this work, we have successfully attained this objective, with the elaborate manipulation of non-interfering pyridine-Pt^(2+) and molecular tweezer/guest complexation in a hierarchical self-assembly manner. The resulting SCCs-based linear supramolecular polymers exhibit intriguing NIR-emissive behaviors, primarily attributed to the presence of intermolecular Pt(Ⅱ)-Pt(Ⅱ) metal-metal interactions in the non-covalent tweezering structure. Hence, supramolecular engineering of multiple non-covalent interactions offers a feasible avenue toward functional materials with tailored properties.
