Background Bovine mastitis is one of the main causes of reduced production in dairy cows.The infection of the mammary gland is mainly caused by the bacterium Staphylococcus aureus,whose resistant strains make the trea...Background Bovine mastitis is one of the main causes of reduced production in dairy cows.The infection of the mammary gland is mainly caused by the bacterium Staphylococcus aureus,whose resistant strains make the treatment of mastitis with conventional antibiotics very difficult and result in high losses.Therefore,it is impor-tant to develop novel therapeutic agents to overcome the resistance of mastitis-causing strains.In this study,novel selenium-tellurium based nanoparticles(SeTeNPs)were synthesized and characterized.Their antibacterial activity and biocompatibility were evaluated both in vitro and in vivo using a bovine model.A total of 10 heifers were divided into experimental and control groups(5 animals each).After intramammary infection with methicillin resistant S.aureus(MRSA)and the development of clinical signs of mastitis,a dose of SeTeNPs was administered to all quarters in the experimental group.Results Based on in vitro tests,the concentration of 149.70 mg/L and 263.95 mg/L of Se and Te,respectively,was used for application into the mammary gland.Three days after SeTeNPs administration,MRSA counts in the experimental group showed a significant reduction(P<0.01)compared to the control group.The inhibitory effect observed within the in vitro experiments was thus confirmed,resulting in the suppression of infection in ani-mals.Moreover,the superior biocompatibility of SeTeNPs in the organism was demonstrated,as the nanoparticles did not significantly alter the inflammatory response or histopathology at the site of application,i.e.,mammary gland,compared to the control group(P>0.05).Additionally,the metabolic profile of the blood plasma as well as the histology of the main organs remained unaffected,indicating that the nanoparticles had no adverse effects on the organism.Conclusions Our findings suggest that SeTeNPs can be used as a promising treatment for bovine mastitis in the pres-ence of resistant bacteria.However,the current study is limited by its small sample size,making it primarily a proof of the concept for the efficacy of intramammary-applied SeTeNPs.Therefore,further research with a larger sample size is needed to validate these results.展开更多
The small-molecule alkaloid halofuginone(HF)is obtained from febrifugine.Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic function...The small-molecule alkaloid halofuginone(HF)is obtained from febrifugine.Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic functions,which range from parasite infections and fibrosis to autoimmune diseases.In particular,HF is believed to play an excellent anticancer role by suppressing the proliferation,adhesion,metastasis,and invasion of cancers.This review supports the goal of demonstrating various anticancer effects and molecular mechanisms of HF.In the studies covered in this review,the anticancer molecular mechanisms of HF mainly included transforming growth factor-β(TGF-β)/Smad-3/nuclear factor erythroid 2-related factor 2(Nrf2),serine/threonine kinase proteins(Akt)/mechanistic target of rapamycin complex 1(mTORC1)/wingless/integrated(Wnt)/β-catenin,the exosomal microRNA-31(miR-31)/histone deacetylase 2(HDAC2)signaling pathway,and the interaction of the extracellular matrix(ECM)and immune cells.Notably,HF,as a novel type of adenosine triphosphate(ATP)-dependent inhibitor that is often combined with prolyl transfer RNA synthetase(ProRS)and amino acid starvation therapy(AAS)to suppress the formation of ribosome,further exerts a significant effect on the tumor microenvironment(TME).Additionally,the combination of HF with other drugs or therapies obtained universal attention.Our results showed that HF has significant potential for clinical cancer treatment.展开更多
Inhibition of foam cell formation is considered a promising treatment method for atherosclerosis,the leading cause of cardiovascular diseases worldwide.However,currently available therapeutic strategies have shown uns...Inhibition of foam cell formation is considered a promising treatment method for atherosclerosis,the leading cause of cardiovascular diseases worldwide.However,currently available therapeutic strategies have shown unsatisfactory clinical outcomes.Thus,herein,we design aloperine(ALO)-loaded and hyaluronic acid(HA)-modified palladium(Pd)octahedral nanozymes(Pd@HA/ALO)that can synergistically scavenge reactive oxygen species(ROS)and downregulate cyclooxygenase-2(COX-2)expression to induce macrophage polarization,thus inhibiting foam cell formation to attenuate atherosclerosis.Due to the targeted effect of HA on stabilin-2 and CD44,which are overexpressed in atherosclerotic plaques,Pd@HA/ALO can actively accumulate in atherosclerotic plaques.Subsequently,the antioxidative effects of Pd octahedral nanozymes are mediated by their intrinsic superoxide dismutase-and catalase-like activities capable of effective scavenging of ROS.In addition,anti-inflammatory effects are mediated by controlled,on-demand near-infrared-triggered ALO release leading to inhibition of COX-2 expression.Importantly,the combined therapy can promote the polarization of macrophages to the M2 subtype by upregulating Arg-1 and CD206 expression and downregulating expression of TNF-α,IL-1βand IL-6,thereby inhibiting atherosclerosis-related foam cell formation.In conclusion,the presented in vitro and in vivo data demonstrate that Pd@HA/ALO enhanced macrophage polarization to reduce plaque formation,identifying an attractive treatment strategy for cardiovascular disease.展开更多
Background: The high doses of zinc oxide(Zn O) administered orally to piglets for the prevention of diarrhea and increase of growth rate can contaminate pig farms and the surrounding environment. Therefore, there is a...Background: The high doses of zinc oxide(Zn O) administered orally to piglets for the prevention of diarrhea and increase of growth rate can contaminate pig farms and the surrounding environment. Therefore, there is a need to find a replacement of high doses of dietary Zn O with an equally effective alternative. In the present study, the effect of two formulations of zinc phosphate-based nanoparticles(Zn A and Zn C NPs) on growth performance,intestinal microbiota, antioxidant status, and intestinal and liver morphology was evaluated. A total of 100 weaned piglets were randomly divided into 10 equal groups with the base diet(control) or the base diet supplemented with Zn A, Zn C, or Zn O at concentrations 500, 1000, and 2000 mg Zn per kilogram of diet. Supplements were given to animals for 10 days. Fecal samples were collected on day 0, 5, 10 and 20. At the end of the treatment(day 10),three piglets from each group were sacrificed and analyzed.Results: Comparing to that of control, the significantly higher piglet weight gain was observed in all piglet groups fed with Zn A(P < 0.05). Differences in the total aerobic bacteria and coliform counts in piglet feces after NPs supplementation compared to that of control and Zn O groups were also found(P < 0.05). The majority of aerobic culturable bacteria from the feces represented Escherichia(28.57–47.62%), Enterococcus(3.85–35.71%), and Streptococcus(3.70–42.31%) spp. A total of 542 Escherichia coli isolates were screened for the virulence genes STa,STb, Stx2, F4, and F18. The substantial occurrence of E. coli virulence factors was found on day 5, mainly in fimbrillary antigen and thermostable toxins, except for piglets fed by Zn C. Zn treatment decreased Zn blood levels in piglets fed with Zn O and Zn A(500 mg/kg) and increased in Zn C(2000 mg/kg) compared to that of control(P < 0.05). The antioxidant status of piglets was affected only by Zn A. While some changes in the liver and the intestinal morphology of piglets with NPs were observed, none were serious as reflected by the normal health status and increased weigh gain performance.Conclusions: Our results indicate that Zn A NPs have a positive effect on the piglet growth performance even at the lowest concentration. The prevalence of E. coli virulence factors was lowest in pigs supplemented with Zn C.Zinc phosphate-based nanoparticles may be an effective alternative to Zn O.展开更多
Background: Development of new nanomaterials that inhibit or kil bacteria is an important and timely research topic. For example, financial losses due to infectious diseases, such as diarrhea, are a major concern in l...Background: Development of new nanomaterials that inhibit or kil bacteria is an important and timely research topic. For example, financial losses due to infectious diseases, such as diarrhea, are a major concern in livestock productions around the world. Antimicrobial nanoparticles(NPs) represent a promising alternative to antibiotics and may lower antibiotic use and consequently spread of antibiotic resistance traits among bacteria, including pathogens.Results: Four formulations of zinc nanoparticles(Zn A, Zn B, Zn C, and Zn D) based on phosphates with spherical(Zn A, Zn B)or irregular(Zn C, Zn D) morphology were prepared. The highest in vitro inhibitory effect of our NPs was observed against Staphylococcus aureus(inhibitory concentration values, IC50, ranged from 0.5 to 1.6 mmol/L), fol owed by Escherichia coli(IC500.8–1.5 mmol/L). In contrast, methicil in resistant S. aureus(IC501.2–4.7 mmol/L) was least affected and this was similar to inhibitory patterns of commercial Zn O-based NPs and Zn O. After the successful in vitro testing, the in vivo study with rats based on dietary supplementation with zinc NPs was conducted. Four groups of rats were treated by 2,000 mg Zn/kg diet of Zn A, Zn B, Zn C, and Zn D, for comparison two groups were supplemented by 2,000 mg Zn/kg diet of Zn O-N and Zn O, and one group(control) was fed only by basal diet. The significantly higher(P < 0.05) Zn level in liver and kidney of al treated groups was found, nevertheless Zn NPs did not greatly influence antioxidant status of rats. However,the total aerobic and coliform bacterial population in rat feces significantly decreased(P < 0.05) in al zinc groups after 30 d of the treatment. Furthermore, when compared to the Zn O group, Zn A and Zn C nanoparticles reduced coliforms significantly more(P < 0.05).Conclusions: Our results demonstrate that phosphate-based zinc nanoparticles have the potential to act as antibiotic agents.展开更多
The aim of the study was to evaluate the effect of 1.5% herb supplement of RL （rosemary leaves）, YB （yarrow blooms）, PL （plantain leaves）, OS （oreganos talks） or red GP （grape pomace） on the broiler liver an...The aim of the study was to evaluate the effect of 1.5% herb supplement of RL （rosemary leaves）, YB （yarrow blooms）, PL （plantain leaves）, OS （oreganos talks） or red GP （grape pomace） on the broiler liver antioxidant activity. Samples were analyzed by FRAP （ferric-reducing antioxidant power）, FRK （free radicals） and DPPH （2,2-diphenyl-l-picrylhydrazyl） methods. Oxidative stress values （metallo thionein, reduced glutathione, oxidized glutathione and reduced/oxidized glutation ration） were measured in the blood and liver. Biochemical parameters （serum albumin, uric acid and bilirubin） were monitored in the blood. The antioxidant activity measured by the FRK method was higher in the oregano supplement （P 〈 0.05） than in plantain and rosemary supplements.展开更多
Liver fibrosis is a reversible pathological process caused by chronic liver damage and a major risk factor for hepatocellular carcinoma(HCC).Hepatic stellate cell(HSC)activation is considered the main target for liver...Liver fibrosis is a reversible pathological process caused by chronic liver damage and a major risk factor for hepatocellular carcinoma(HCC).Hepatic stellate cell(HSC)activation is considered the main target for liver fibrosis therapy.However,the efficiency of this strategy is limited due to the complex microenvironment of liver fibrosis,including excessive extracellular matrix(ECM)deposition and hypoxia-induced imbalanced ECM metabolism.Herein,nilotinib(NIL)-loaded hyaluronic acid(HA)-coated Ag@Pt nanotriangular nanozymes(APNH NTs)were developed to inhibit HSCs activation and remodel the microenvironment of liver fibrosis.APNH NTs efficiently eliminated intrahepatic reactive oxygen species(ROS)due to their inherent superoxide dismutase(SOD)and catalase(CAT)activities,thereby downregulating the expression of NADPH oxidase-4(NOX-4)and inhibiting HSCs activation.Simultaneously,the oxygen produced by the APNH NTs further alleviated the hypoxic microenvironment.Importantly,the released NIL promoted collagen depletion by suppressing the expression of tissue inhibitor of metalloproteinase-1(TIMP-1),thus synergistically remodeling the microenvironment of liver fibrosis.Notably,an in vivo study in CCl_(4)-induced mice revealed that APNH NTs exhibited significant antifibrogenic effects without obvious long-term toxicity.Taken together,the data from this work suggest that treatment with the synthesized APNH NTs provides an enlightening strategy for remodeling the microenvironment of liver fibrosis with boosted antifibrogenic activity.展开更多
Although the general concept of nanotechnology relies on exploitation of size-dependent properties of nanoscaled materials,the relation between the size/morphology of nanoparticles with their biological activity remai...Although the general concept of nanotechnology relies on exploitation of size-dependent properties of nanoscaled materials,the relation between the size/morphology of nanoparticles with their biological activity remains not well understood.Therefore,we aimed at investigating the biological activity of Se nanoparticles,one of the most promising candidates of nanomaterials for biomedicine,possessing the same crystal structure,but differing in morphology(nanorods vs.spherical particles)and aspect ratios(AR,11.5 vs.22.3 vs.1.0)in human cells and BALB/c mice.Herein,we report that in case of nanorod-shaped Se nanomaterials,AR is a critical factor describing their cytotoxicity and biocompatibility.However,spherical nanoparticles(AR 1.0)do not fit this statement and exhibit markedly higher cytotoxicity than lower-AR Se nanorods.Beside of cytotoxicity,we also show that morphology and size substantially affect the uptake and intracellular fate of Se nanomaterials.In line with in vitro data,in vivo i.v.administration of Se nanomaterials revealed the highest toxicity for higher-AR nanorods followed by spherical nanoparticles and lower-AR nanorods.Moreover,we revealed that Se nanomaterials are able to alter intracellular redox homeostasis,and affect the acidic intracellular vesicles and cytoskeletal architecture in a size-and morphology-dependent manner.Although the tested nanoparticles were produced from the similar sources,their behavior differs markedly,since each type is promising for several various application scenarios,and the presented testing protocol could serve as a concept standardizing the biological relevance of the size and morphology of the various types of nanomaterials and nanoparticles.展开更多
Nanoparticle-mediated targeted delivery of drugs might significantly reduce the dosage and optimize their release properties,increase specificity and bioavailability,improve shelf life,and reduce toxicity.Some nanodru...Nanoparticle-mediated targeted delivery of drugs might significantly reduce the dosage and optimize their release properties,increase specificity and bioavailability,improve shelf life,and reduce toxicity.Some nanodrugs are able to overcome the blood-brain barrier that is an obstacle to treatment of brain tumors.Vessels in tumors have abnormal architecture and are highly permeable;moreover,tumors also have poor lymphatic drainage,allowing for accumulation of macromolecules greater than approximately 40 kDa within the tumor microenvironment.Nanoparticles exploit this feature,known as the enhanced permeability and retention effect,to target solid tumors.Active targeting,i.e.surface modification of nanoparticles,is a way to decrease uptake in normal tissue and increase accumulation in a tumor,and it usually involves targeting surface membrane proteins that are upregulated in cancer cells.The targeting molecules are typically antibodies or their fragments;aptamers;oligopeptides or small molecules.There are currently several FDA-approved nanomedicines,but none approved for brain tumor therapy.This review,based both on the study of literature and on the authors own experimental work describes a comprehensive overview of preclinical and clinical research of nanodrugs in therapy of brain tumors.展开更多
基金Financial support from ERDF “Multidisciplinary research to increase application potential of nanomaterials in agricultural practice” (No.CZ.02.1.01/0.0/0.0/16_025/0007314)the assistance provided by the Research Infrastructure Nano Envi Cz, supported by the Ministry of Education, Youth and Sports of the Czech Republic under Project No. LM2018124+4 种基金Czech Nano Lab Research Infrastructure supported by MEYS CR (LM2023051)Grant Agency of Gregor Johann Mendel (C-MNG-23–002)further supported by the Ministry of Agriculture of the Czech Republic by Grant RO0523Internal Grant Agency of University of Veterinary Sciences Brno (223/2024/FVHE)the National Institute of Virology and Bacteriology project (Programme EXCELES, Project ID No. LX22NPO5103)-Funded by the European Union-Next Generation EU.
文摘Background Bovine mastitis is one of the main causes of reduced production in dairy cows.The infection of the mammary gland is mainly caused by the bacterium Staphylococcus aureus,whose resistant strains make the treatment of mastitis with conventional antibiotics very difficult and result in high losses.Therefore,it is impor-tant to develop novel therapeutic agents to overcome the resistance of mastitis-causing strains.In this study,novel selenium-tellurium based nanoparticles(SeTeNPs)were synthesized and characterized.Their antibacterial activity and biocompatibility were evaluated both in vitro and in vivo using a bovine model.A total of 10 heifers were divided into experimental and control groups(5 animals each).After intramammary infection with methicillin resistant S.aureus(MRSA)and the development of clinical signs of mastitis,a dose of SeTeNPs was administered to all quarters in the experimental group.Results Based on in vitro tests,the concentration of 149.70 mg/L and 263.95 mg/L of Se and Te,respectively,was used for application into the mammary gland.Three days after SeTeNPs administration,MRSA counts in the experimental group showed a significant reduction(P<0.01)compared to the control group.The inhibitory effect observed within the in vitro experiments was thus confirmed,resulting in the suppression of infection in ani-mals.Moreover,the superior biocompatibility of SeTeNPs in the organism was demonstrated,as the nanoparticles did not significantly alter the inflammatory response or histopathology at the site of application,i.e.,mammary gland,compared to the control group(P>0.05).Additionally,the metabolic profile of the blood plasma as well as the histology of the main organs remained unaffected,indicating that the nanoparticles had no adverse effects on the organism.Conclusions Our findings suggest that SeTeNPs can be used as a promising treatment for bovine mastitis in the pres-ence of resistant bacteria.However,the current study is limited by its small sample size,making it primarily a proof of the concept for the efficacy of intramammary-applied SeTeNPs.Therefore,further research with a larger sample size is needed to validate these results.
基金supported by the National Natural Science Foundation of China(Grant No.:32172918)the project funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,China,and the Key Projects of Natural Science Foundation of Anhui Provincial Department of Education,China(Grant No.:2023AH051017)the Anhui Agricultural University Talent Research Grant Project(Project No.:RC393302).
文摘The small-molecule alkaloid halofuginone(HF)is obtained from febrifugine.Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic functions,which range from parasite infections and fibrosis to autoimmune diseases.In particular,HF is believed to play an excellent anticancer role by suppressing the proliferation,adhesion,metastasis,and invasion of cancers.This review supports the goal of demonstrating various anticancer effects and molecular mechanisms of HF.In the studies covered in this review,the anticancer molecular mechanisms of HF mainly included transforming growth factor-β(TGF-β)/Smad-3/nuclear factor erythroid 2-related factor 2(Nrf2),serine/threonine kinase proteins(Akt)/mechanistic target of rapamycin complex 1(mTORC1)/wingless/integrated(Wnt)/β-catenin,the exosomal microRNA-31(miR-31)/histone deacetylase 2(HDAC2)signaling pathway,and the interaction of the extracellular matrix(ECM)and immune cells.Notably,HF,as a novel type of adenosine triphosphate(ATP)-dependent inhibitor that is often combined with prolyl transfer RNA synthetase(ProRS)and amino acid starvation therapy(AAS)to suppress the formation of ribosome,further exerts a significant effect on the tumor microenvironment(TME).Additionally,the combination of HF with other drugs or therapies obtained universal attention.Our results showed that HF has significant potential for clinical cancer treatment.
基金supported by the Young Elite Scientists Sponsorship Program by Tianjin(No.0701320001)the Major Special Projects(No.0402080005)+1 种基金the financial support from the CEITEC 2020 Project(No.LQ1601)the Ministry of Education,Youth and Sports of the Czech Republic under the National Sustainability ProgrammeⅡand by ERDF(No.CZ.02.1.01/0.0/0.0/16_025/0007314)。
文摘Inhibition of foam cell formation is considered a promising treatment method for atherosclerosis,the leading cause of cardiovascular diseases worldwide.However,currently available therapeutic strategies have shown unsatisfactory clinical outcomes.Thus,herein,we design aloperine(ALO)-loaded and hyaluronic acid(HA)-modified palladium(Pd)octahedral nanozymes(Pd@HA/ALO)that can synergistically scavenge reactive oxygen species(ROS)and downregulate cyclooxygenase-2(COX-2)expression to induce macrophage polarization,thus inhibiting foam cell formation to attenuate atherosclerosis.Due to the targeted effect of HA on stabilin-2 and CD44,which are overexpressed in atherosclerotic plaques,Pd@HA/ALO can actively accumulate in atherosclerotic plaques.Subsequently,the antioxidative effects of Pd octahedral nanozymes are mediated by their intrinsic superoxide dismutase-and catalase-like activities capable of effective scavenging of ROS.In addition,anti-inflammatory effects are mediated by controlled,on-demand near-infrared-triggered ALO release leading to inhibition of COX-2 expression.Importantly,the combined therapy can promote the polarization of macrophages to the M2 subtype by upregulating Arg-1 and CD206 expression and downregulating expression of TNF-α,IL-1βand IL-6,thereby inhibiting atherosclerosis-related foam cell formation.In conclusion,the presented in vitro and in vivo data demonstrate that Pd@HA/ALO enhanced macrophage polarization to reduce plaque formation,identifying an attractive treatment strategy for cardiovascular disease.
基金Financial support from NAZV QK1720349 “Nanoparticles zinc as an alternative to antibiotics in pigs”ERDF “Multidisciplinary research to increase application potential of nanomaterials in agricultural practice”(No.CZ.02.1.01/0.0/0.0/16_025/0007314)+1 种基金also supported by Internal Grant Agency of Mendel University in Brno(AF-IGA2019-TP006)by CEITEC 2020 (LQ1601)。
文摘Background: The high doses of zinc oxide(Zn O) administered orally to piglets for the prevention of diarrhea and increase of growth rate can contaminate pig farms and the surrounding environment. Therefore, there is a need to find a replacement of high doses of dietary Zn O with an equally effective alternative. In the present study, the effect of two formulations of zinc phosphate-based nanoparticles(Zn A and Zn C NPs) on growth performance,intestinal microbiota, antioxidant status, and intestinal and liver morphology was evaluated. A total of 100 weaned piglets were randomly divided into 10 equal groups with the base diet(control) or the base diet supplemented with Zn A, Zn C, or Zn O at concentrations 500, 1000, and 2000 mg Zn per kilogram of diet. Supplements were given to animals for 10 days. Fecal samples were collected on day 0, 5, 10 and 20. At the end of the treatment(day 10),three piglets from each group were sacrificed and analyzed.Results: Comparing to that of control, the significantly higher piglet weight gain was observed in all piglet groups fed with Zn A(P < 0.05). Differences in the total aerobic bacteria and coliform counts in piglet feces after NPs supplementation compared to that of control and Zn O groups were also found(P < 0.05). The majority of aerobic culturable bacteria from the feces represented Escherichia(28.57–47.62%), Enterococcus(3.85–35.71%), and Streptococcus(3.70–42.31%) spp. A total of 542 Escherichia coli isolates were screened for the virulence genes STa,STb, Stx2, F4, and F18. The substantial occurrence of E. coli virulence factors was found on day 5, mainly in fimbrillary antigen and thermostable toxins, except for piglets fed by Zn C. Zn treatment decreased Zn blood levels in piglets fed with Zn O and Zn A(500 mg/kg) and increased in Zn C(2000 mg/kg) compared to that of control(P < 0.05). The antioxidant status of piglets was affected only by Zn A. While some changes in the liver and the intestinal morphology of piglets with NPs were observed, none were serious as reflected by the normal health status and increased weigh gain performance.Conclusions: Our results indicate that Zn A NPs have a positive effect on the piglet growth performance even at the lowest concentration. The prevalence of E. coli virulence factors was lowest in pigs supplemented with Zn C.Zinc phosphate-based nanoparticles may be an effective alternative to Zn O.
基金Financial support from ERDF “Multidisciplinary research to increase application potential of nanomaterials in agricultural practice”(No.CZ.02.1.01/0.0/0.0/16_025/0007314)supported by NAZV QK1720349 “Nanoparticles zinc as an alternative to antibiotics in pigs”AF-IGA-2018-tym001 “Comparison of the impact of climate change on photosynthesis C3 and C4 plants cycles which are used in livestock feed”
文摘Background: Development of new nanomaterials that inhibit or kil bacteria is an important and timely research topic. For example, financial losses due to infectious diseases, such as diarrhea, are a major concern in livestock productions around the world. Antimicrobial nanoparticles(NPs) represent a promising alternative to antibiotics and may lower antibiotic use and consequently spread of antibiotic resistance traits among bacteria, including pathogens.Results: Four formulations of zinc nanoparticles(Zn A, Zn B, Zn C, and Zn D) based on phosphates with spherical(Zn A, Zn B)or irregular(Zn C, Zn D) morphology were prepared. The highest in vitro inhibitory effect of our NPs was observed against Staphylococcus aureus(inhibitory concentration values, IC50, ranged from 0.5 to 1.6 mmol/L), fol owed by Escherichia coli(IC500.8–1.5 mmol/L). In contrast, methicil in resistant S. aureus(IC501.2–4.7 mmol/L) was least affected and this was similar to inhibitory patterns of commercial Zn O-based NPs and Zn O. After the successful in vitro testing, the in vivo study with rats based on dietary supplementation with zinc NPs was conducted. Four groups of rats were treated by 2,000 mg Zn/kg diet of Zn A, Zn B, Zn C, and Zn D, for comparison two groups were supplemented by 2,000 mg Zn/kg diet of Zn O-N and Zn O, and one group(control) was fed only by basal diet. The significantly higher(P < 0.05) Zn level in liver and kidney of al treated groups was found, nevertheless Zn NPs did not greatly influence antioxidant status of rats. However,the total aerobic and coliform bacterial population in rat feces significantly decreased(P < 0.05) in al zinc groups after 30 d of the treatment. Furthermore, when compared to the Zn O group, Zn A and Zn C nanoparticles reduced coliforms significantly more(P < 0.05).Conclusions: Our results demonstrate that phosphate-based zinc nanoparticles have the potential to act as antibiotic agents.
文摘The aim of the study was to evaluate the effect of 1.5% herb supplement of RL （rosemary leaves）, YB （yarrow blooms）, PL （plantain leaves）, OS （oreganos talks） or red GP （grape pomace） on the broiler liver antioxidant activity. Samples were analyzed by FRAP （ferric-reducing antioxidant power）, FRK （free radicals） and DPPH （2,2-diphenyl-l-picrylhydrazyl） methods. Oxidative stress values （metallo thionein, reduced glutathione, oxidized glutathione and reduced/oxidized glutation ration） were measured in the blood and liver. Biochemical parameters （serum albumin, uric acid and bilirubin） were monitored in the blood. The antioxidant activity measured by the FRK method was higher in the oregano supplement （P 〈 0.05） than in plantain and rosemary supplements.
基金supported by the Young Elite Scientists Sponsorship Program by Tianjin(No.0701320001,China)Major Special Projects(No.0402080005,China)+2 种基金National Key R&D Program of China(No.2020YFC1512304,China)National Natural Science of China(Nos.82273873,31971106,and 81372124,China)the Czech Health Council(AZV NU12J-08-00043,Czech).
文摘Liver fibrosis is a reversible pathological process caused by chronic liver damage and a major risk factor for hepatocellular carcinoma(HCC).Hepatic stellate cell(HSC)activation is considered the main target for liver fibrosis therapy.However,the efficiency of this strategy is limited due to the complex microenvironment of liver fibrosis,including excessive extracellular matrix(ECM)deposition and hypoxia-induced imbalanced ECM metabolism.Herein,nilotinib(NIL)-loaded hyaluronic acid(HA)-coated Ag@Pt nanotriangular nanozymes(APNH NTs)were developed to inhibit HSCs activation and remodel the microenvironment of liver fibrosis.APNH NTs efficiently eliminated intrahepatic reactive oxygen species(ROS)due to their inherent superoxide dismutase(SOD)and catalase(CAT)activities,thereby downregulating the expression of NADPH oxidase-4(NOX-4)and inhibiting HSCs activation.Simultaneously,the oxygen produced by the APNH NTs further alleviated the hypoxic microenvironment.Importantly,the released NIL promoted collagen depletion by suppressing the expression of tissue inhibitor of metalloproteinase-1(TIMP-1),thus synergistically remodeling the microenvironment of liver fibrosis.Notably,an in vivo study in CCl_(4)-induced mice revealed that APNH NTs exhibited significant antifibrogenic effects without obvious long-term toxicity.Taken together,the data from this work suggest that treatment with the synthesized APNH NTs provides an enlightening strategy for remodeling the microenvironment of liver fibrosis with boosted antifibrogenic activity.
基金support from ERDF"Multidisciplinary research to increase application potential of nanomaterials in agricultural practice"(No.CZ.02.1.01/0.0/0.0/16_025/0007314)is gratefully acknowledgedWe also acknowledge CF Nanobiotechnology(project no.LM2018127)and Research Infrastructure NanoEnviCz(project no.LM2018124)both supported by MEYS CR for perfect assistance with physico-chemical characterization of Se nanomaterialsThe research was also carried out under the project CEITEC 2020(LQ1601)with financial support from the MEYS CR under the National Sustainability Programme II.
文摘Although the general concept of nanotechnology relies on exploitation of size-dependent properties of nanoscaled materials,the relation between the size/morphology of nanoparticles with their biological activity remains not well understood.Therefore,we aimed at investigating the biological activity of Se nanoparticles,one of the most promising candidates of nanomaterials for biomedicine,possessing the same crystal structure,but differing in morphology(nanorods vs.spherical particles)and aspect ratios(AR,11.5 vs.22.3 vs.1.0)in human cells and BALB/c mice.Herein,we report that in case of nanorod-shaped Se nanomaterials,AR is a critical factor describing their cytotoxicity and biocompatibility.However,spherical nanoparticles(AR 1.0)do not fit this statement and exhibit markedly higher cytotoxicity than lower-AR Se nanorods.Beside of cytotoxicity,we also show that morphology and size substantially affect the uptake and intracellular fate of Se nanomaterials.In line with in vitro data,in vivo i.v.administration of Se nanomaterials revealed the highest toxicity for higher-AR nanorods followed by spherical nanoparticles and lower-AR nanorods.Moreover,we revealed that Se nanomaterials are able to alter intracellular redox homeostasis,and affect the acidic intracellular vesicles and cytoskeletal architecture in a size-and morphology-dependent manner.Although the tested nanoparticles were produced from the similar sources,their behavior differs markedly,since each type is promising for several various application scenarios,and the presented testing protocol could serve as a concept standardizing the biological relevance of the size and morphology of the various types of nanomaterials and nanoparticles.
基金supported by GACR(NANOCHEMO 14-8344S)by the Ministry of Health of the Czech Republic for conceptual development of research organization 00064203(University Hospital Motol,Prague,Czech Republic).
文摘Nanoparticle-mediated targeted delivery of drugs might significantly reduce the dosage and optimize their release properties,increase specificity and bioavailability,improve shelf life,and reduce toxicity.Some nanodrugs are able to overcome the blood-brain barrier that is an obstacle to treatment of brain tumors.Vessels in tumors have abnormal architecture and are highly permeable;moreover,tumors also have poor lymphatic drainage,allowing for accumulation of macromolecules greater than approximately 40 kDa within the tumor microenvironment.Nanoparticles exploit this feature,known as the enhanced permeability and retention effect,to target solid tumors.Active targeting,i.e.surface modification of nanoparticles,is a way to decrease uptake in normal tissue and increase accumulation in a tumor,and it usually involves targeting surface membrane proteins that are upregulated in cancer cells.The targeting molecules are typically antibodies or their fragments;aptamers;oligopeptides or small molecules.There are currently several FDA-approved nanomedicines,but none approved for brain tumor therapy.This review,based both on the study of literature and on the authors own experimental work describes a comprehensive overview of preclinical and clinical research of nanodrugs in therapy of brain tumors.
