Ischemic stroke is the leading cause of death in China,accounting for approximately one-third of all stroke-associated deaths worldwide.Currently,thrombolysis is employed for ischemic strokes.However,due to the limite...Ischemic stroke is the leading cause of death in China,accounting for approximately one-third of all stroke-associated deaths worldwide.Currently,thrombolysis is employed for ischemic strokes.However,due to the limited therapeutic window of thrombolytic agents,most patients do not receive the drug at the right time.Moreover,these agents are associated with risks of hemorrhage and reperfusion damage.Herein,Angiopep-2(ANG)-black phosphorus(BP)-resveratrol(RES),a drug-loaded system,was used to deliver drugs across the blood–brain barrier(BBB).ANG-BP-RES has a uniform size,stable structure,good photothermal effect,and strong drug release ability under near-infrared(NIR)irradiation and acidic conditions.Furthermore,ANG-BP-RES can efficiently target the brain and improve BBB permeability,exerting a significant therapeutic effect against ischemic brain injury,especially after NIR irradiation.ANG-BP-RES is also biocompatible and shows minimal toxicity toward cells and tissues.This study offers novel insights into the therapeutic management of ischemic brain injury.展开更多
BACKGROUND As a member of the chaperonin-containing tailless complex polypeptide 1(TCP1)complex,which plays a pivotal role in ensuring the accurate folding of numerous proteins,chaperonin-containing TCP1 subunit 6A(CC...BACKGROUND As a member of the chaperonin-containing tailless complex polypeptide 1(TCP1)complex,which plays a pivotal role in ensuring the accurate folding of numerous proteins,chaperonin-containing TCP1 subunit 6A(CCT6A)participates in various physiological and pathological processes.However,its effects on cell death and cancer therapy and the underlying mechanisms need further exploration in colorectal cancer(CRC)cells.AIM To explore the effects of CCT6A on cell death and cancer therapy and the underlying mechanisms in CRC.METHODS Cell proliferation was evaluated using the MTS assay,EdU staining,and colony growth assays.The expression of CCT6A was monitored by immunoblotting and quantitative PCR.CCT6A was knocked out by CRISPR-Cas9,and overexpressed by transfecting plasmids.Autophagy was examined by immunoblotting and the mCherry-GFP-LC3 assay.To monitor apoptosis and necroptosis,immunoblotting,co-immunoprecipitation,and flow cytometry were employed.RESULTS Cisplatin(DDP)exerted cytotoxic effects on CRC cells while simultaneously downregulating the expression of CCT6A.Depletion of CCT6A amplified the cytotoxic effects of DDP,whereas overexpression of CCT6A attenuated these adverse effects.CCT6A suppressed autophagy,apoptosis,and necroptosis under both basal and DDP-treated conditions.Autophagy inhibitors significantly enhanced the cytotoxic effects of DDP,whereas a necroptosis inhibitor partially reversed the cell viability loss induced by DDP.Furthermore,inhibiting autophagy enhanced both apoptosis and necroptosis induced by DDP.CONCLUSION CCT6A negatively modulates autophagy,apoptosis,and necroptosis,and CCT6A confers resistance to DDP therapy in CRC,suggesting its potential as a therapeutic target.展开更多
Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2...Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2DM.Various considerations can make selecting and switching between different GLP-1 RAs challenging.Our study aims to provide a comprehensive guide for the usage of GLP-1 RAs and dual GIP and GLP-1 RAs for the management of T2DM.展开更多
Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases ...Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases has become a topic of intense research interest.This study revealed the mechanism underlying the protective effect of the dominant polypeptide PKKVV(Pro-Lys-Lys-Val-Val)of Rhopilema esculentum cnidoblasts against DSS-induced UC through a combined analysis of the metagenome and serum metabolome.Specifically,the polypeptide composition of R.esculentum cnidoblasts was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF/TOF-MS).Molecular docking showed that the dominant peptide PKKVV could bind better with tumor necrosis factor-α(TNF-α)than the original ligand.Subsequent animal experiments suggested that PKKVV could modulate disorganized gut microorganisms in mice with UC;affect serum metabolites through the arachidonic acid,glycerophospholipid and linoleic acid metabolism pathways;and further alleviate UC symptoms.This study provides a reference for the comprehensive development of marine bioactive substances and nonpharmaceutical treatments for UC.展开更多
In order to study the action mechanism of Sacha Inchi polypeptide in liquid crystal emulsion,oil-in-water liquid crystal emulsions with Sacha Inchi fermented polypeptide as the active component were prepared.The micro...In order to study the action mechanism of Sacha Inchi polypeptide in liquid crystal emulsion,oil-in-water liquid crystal emulsions with Sacha Inchi fermented polypeptide as the active component were prepared.The microstructures,particle sizes,stabilities,thermodynamic properties,and rheological properties of liquid crystal emulsions with different concentrations of the fermentation products were observed by Polarizing microscope,Particle size meter,Thermogravimetric differential thermal synchronous measurement system,and Rheometer,respectively.The results showed that the average particle size of fermented peptide liquid crystal emulsion was(25.7±2.8)μm,and the liquid crystal structure was complete and stable.The content of bound water and liquid crystal in the emulsion with 1%Sacha Inchi polypeptide were higher than those in the blank emulsion and the emulsions with 3%and 5%Sacha Inchi polypeptide.Rheological results indicated that the viscosity of liquid crystal emulsion with the change curve of shear rate registered the shear thinning phenomenon,which belongs to non-Newtonian fluid.The hysteresis area,energy storage modulus,and loss modulus of the 1%additive amount of liquid crystal emulsion were larger than those of the blank emulsion and the emulsions with 3%and 5%Sacha Inchi polypeptide,indicating greater thixotropy and stronger shear resistance.The hydrophilic amino acid residues of the peptide in the 1%additive amount of the emulsion were combined with the water phase,while the hydrophobic amino acid residues of the peptide entered the oil phase,which formed a viscoelastic film at the oil-water interface,so that the liquid crystal emulsion had a more stable gel network structure.展开更多
Excessive secretion of human islet amyloid polypeptide(hIAPP)is an important pathological basis of diabetic encephalopathy(DE).In this study,we aimed to investigate the potential implications of hIAPP in DE pathogenes...Excessive secretion of human islet amyloid polypeptide(hIAPP)is an important pathological basis of diabetic encephalopathy(DE).In this study,we aimed to investigate the potential implications of hIAPP in DE pathogenesis.Brain magnetic resonance imaging and cognitive scales were applied to evaluate white matter damage and cognitive function.We found that the concentration of serum hIAPP was positively correlated with white matter damage but negatively correlated with cognitive scores in patients with type 2 diabetes mellitus.In vitro assays revealed that oligodendrocytes,compared with neurons,were more prone to acidosis under exogenous hIAPP stimulation.Moreover,western blotting and co-immunoprecipitation indicated that hIAPP interfered with the binding process of monocarboxylate transporter(MCT)1 to its accessory protein CD147 but had no effect on the binding of MCT2 to its accessory protein gp70.Proteomic differential analysis of proteins co-immunoprecipitated with CD147 in oligodendrocytes revealed Yeast Rab GTPase-Interacting protein 2(YIPF2,which modulates the transfer of CD147 to the cell membrane)as a significant target.Furthermore,YIPF2 inhibition significantly improved hIAPP-induced acidosis in oligodendrocytes and alleviated cognitive dysfunction in DE model mice.These findings suggest that increased CD147 translocation by inhibition of YIPF2 optimizes MCT1 and CD147 binding,potentially ameliorating hIAPP-induced acidosis and the consequent DE-related demyelination.展开更多
基金funded by the National Natural Science Foundation of China (No. 81960334)the Guiding Plan of Xinjiang Production Construction Corps (No. 2022ZD007)+4 种基金the Science and Technology Innovation Leading Talents Program of Guangdong Province (No. 2019TX05C343)the Basic and Applied Basic Research Foundation of Guangdong Province-Regional Joint Fund-Key Projects (No. 2019B1515120043)the Project supported by the State Key Laboratory of Luminescence and Applications (No. SKLA-2020-03)the support from Instrumental Analysis Center of Shenzhen University (Xili Campus)Instrumental Analysis Center of Shihezi University.
文摘Ischemic stroke is the leading cause of death in China,accounting for approximately one-third of all stroke-associated deaths worldwide.Currently,thrombolysis is employed for ischemic strokes.However,due to the limited therapeutic window of thrombolytic agents,most patients do not receive the drug at the right time.Moreover,these agents are associated with risks of hemorrhage and reperfusion damage.Herein,Angiopep-2(ANG)-black phosphorus(BP)-resveratrol(RES),a drug-loaded system,was used to deliver drugs across the blood–brain barrier(BBB).ANG-BP-RES has a uniform size,stable structure,good photothermal effect,and strong drug release ability under near-infrared(NIR)irradiation and acidic conditions.Furthermore,ANG-BP-RES can efficiently target the brain and improve BBB permeability,exerting a significant therapeutic effect against ischemic brain injury,especially after NIR irradiation.ANG-BP-RES is also biocompatible and shows minimal toxicity toward cells and tissues.This study offers novel insights into the therapeutic management of ischemic brain injury.
基金Supported by Shandong Provincial Natural Science Foundation,No.ZR2023MH329Project of Shandong Province Higher Educational Youth Innovation Science and Technology Program,No.2023KJ263and Natural Science Foundation of Gansu Province,China,No.22JR5RA953.
文摘BACKGROUND As a member of the chaperonin-containing tailless complex polypeptide 1(TCP1)complex,which plays a pivotal role in ensuring the accurate folding of numerous proteins,chaperonin-containing TCP1 subunit 6A(CCT6A)participates in various physiological and pathological processes.However,its effects on cell death and cancer therapy and the underlying mechanisms need further exploration in colorectal cancer(CRC)cells.AIM To explore the effects of CCT6A on cell death and cancer therapy and the underlying mechanisms in CRC.METHODS Cell proliferation was evaluated using the MTS assay,EdU staining,and colony growth assays.The expression of CCT6A was monitored by immunoblotting and quantitative PCR.CCT6A was knocked out by CRISPR-Cas9,and overexpressed by transfecting plasmids.Autophagy was examined by immunoblotting and the mCherry-GFP-LC3 assay.To monitor apoptosis and necroptosis,immunoblotting,co-immunoprecipitation,and flow cytometry were employed.RESULTS Cisplatin(DDP)exerted cytotoxic effects on CRC cells while simultaneously downregulating the expression of CCT6A.Depletion of CCT6A amplified the cytotoxic effects of DDP,whereas overexpression of CCT6A attenuated these adverse effects.CCT6A suppressed autophagy,apoptosis,and necroptosis under both basal and DDP-treated conditions.Autophagy inhibitors significantly enhanced the cytotoxic effects of DDP,whereas a necroptosis inhibitor partially reversed the cell viability loss induced by DDP.Furthermore,inhibiting autophagy enhanced both apoptosis and necroptosis induced by DDP.CONCLUSION CCT6A negatively modulates autophagy,apoptosis,and necroptosis,and CCT6A confers resistance to DDP therapy in CRC,suggesting its potential as a therapeutic target.
文摘Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2DM.Various considerations can make selecting and switching between different GLP-1 RAs challenging.Our study aims to provide a comprehensive guide for the usage of GLP-1 RAs and dual GIP and GLP-1 RAs for the management of T2DM.
基金sponsored by the National Key R&D Program of China (2018YFD0901102)the Natural Science Foundation of Zhejiang Province (LQ22D060002)+2 种基金the Fund of State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products (ZS20190105)the Fundamental Research Funds for the Provincial Universities of Zhejiang (SJLY2021015)the K.C.Wong Magna Fund of Ningbo University。
文摘Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases has become a topic of intense research interest.This study revealed the mechanism underlying the protective effect of the dominant polypeptide PKKVV(Pro-Lys-Lys-Val-Val)of Rhopilema esculentum cnidoblasts against DSS-induced UC through a combined analysis of the metagenome and serum metabolome.Specifically,the polypeptide composition of R.esculentum cnidoblasts was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF/TOF-MS).Molecular docking showed that the dominant peptide PKKVV could bind better with tumor necrosis factor-α(TNF-α)than the original ligand.Subsequent animal experiments suggested that PKKVV could modulate disorganized gut microorganisms in mice with UC;affect serum metabolites through the arachidonic acid,glycerophospholipid and linoleic acid metabolism pathways;and further alleviate UC symptoms.This study provides a reference for the comprehensive development of marine bioactive substances and nonpharmaceutical treatments for UC.
文摘In order to study the action mechanism of Sacha Inchi polypeptide in liquid crystal emulsion,oil-in-water liquid crystal emulsions with Sacha Inchi fermented polypeptide as the active component were prepared.The microstructures,particle sizes,stabilities,thermodynamic properties,and rheological properties of liquid crystal emulsions with different concentrations of the fermentation products were observed by Polarizing microscope,Particle size meter,Thermogravimetric differential thermal synchronous measurement system,and Rheometer,respectively.The results showed that the average particle size of fermented peptide liquid crystal emulsion was(25.7±2.8)μm,and the liquid crystal structure was complete and stable.The content of bound water and liquid crystal in the emulsion with 1%Sacha Inchi polypeptide were higher than those in the blank emulsion and the emulsions with 3%and 5%Sacha Inchi polypeptide.Rheological results indicated that the viscosity of liquid crystal emulsion with the change curve of shear rate registered the shear thinning phenomenon,which belongs to non-Newtonian fluid.The hysteresis area,energy storage modulus,and loss modulus of the 1%additive amount of liquid crystal emulsion were larger than those of the blank emulsion and the emulsions with 3%and 5%Sacha Inchi polypeptide,indicating greater thixotropy and stronger shear resistance.The hydrophilic amino acid residues of the peptide in the 1%additive amount of the emulsion were combined with the water phase,while the hydrophobic amino acid residues of the peptide entered the oil phase,which formed a viscoelastic film at the oil-water interface,so that the liquid crystal emulsion had a more stable gel network structure.
基金supported by the National Natural Science Foundation of China (82100863)Hebei Natural Science Foundation (H2020206643 and H2020206105)+3 种基金Funding project for introducing overseas students of Hebei Province (C20210346)Medical Science Research Project of Hebei Province (20211628)Hebei Province Government-funded Excellent Talents Project in Clinical Medicine (ZF2023029)Spark Scientific Research Project of the First Hospital of Hebei Medical University (XH202004).
文摘Excessive secretion of human islet amyloid polypeptide(hIAPP)is an important pathological basis of diabetic encephalopathy(DE).In this study,we aimed to investigate the potential implications of hIAPP in DE pathogenesis.Brain magnetic resonance imaging and cognitive scales were applied to evaluate white matter damage and cognitive function.We found that the concentration of serum hIAPP was positively correlated with white matter damage but negatively correlated with cognitive scores in patients with type 2 diabetes mellitus.In vitro assays revealed that oligodendrocytes,compared with neurons,were more prone to acidosis under exogenous hIAPP stimulation.Moreover,western blotting and co-immunoprecipitation indicated that hIAPP interfered with the binding process of monocarboxylate transporter(MCT)1 to its accessory protein CD147 but had no effect on the binding of MCT2 to its accessory protein gp70.Proteomic differential analysis of proteins co-immunoprecipitated with CD147 in oligodendrocytes revealed Yeast Rab GTPase-Interacting protein 2(YIPF2,which modulates the transfer of CD147 to the cell membrane)as a significant target.Furthermore,YIPF2 inhibition significantly improved hIAPP-induced acidosis in oligodendrocytes and alleviated cognitive dysfunction in DE model mice.These findings suggest that increased CD147 translocation by inhibition of YIPF2 optimizes MCT1 and CD147 binding,potentially ameliorating hIAPP-induced acidosis and the consequent DE-related demyelination.
