Objective:To explore whether thrombopoietin can exert a protective effect against doxorubicin-induced cardiotoxicity by modulating the sirtuin 1(SIRT1)signaling pathway.Methods:H9c2 cell viability was determined by CC...Objective:To explore whether thrombopoietin can exert a protective effect against doxorubicin-induced cardiotoxicity by modulating the sirtuin 1(SIRT1)signaling pathway.Methods:H9c2 cell viability was determined by CCK-8 and cardiomyocyte apoptosis was detected by TUNEL assay.The protein expressions of SIRT1 and p38 MAPK were measured by Western blot.RT-qPCR was also used to determine SIRT1 mRNA expression.In addition,intracellular reactive oxygen species levels and antioxidant enzyme activities were evaluated.Results:Thrombopoietin treatment reversed doxorubicin-induced decline in H9c2 cell viability.It also increased SIRT1 and decreased p-p38 MAPK protein expressions.In addition,thrombopoietin significantly attenuated doxorubicin-induced apoptosis and oxidative stress,and enhanced antioxidant enzyme activities.However,silencing SIRT1 abrogated the protective effects of thrombopoietin,as evidenced by reduced cell viability and increased oxidative stress and reactive oxygen species levels.Conclusions:Thrombopoietin alleviates doxorubicin-induced cardiomyocyte injury by reducing oxidative stress and apoptosis via the SIRT1/p38 MAPK pathway.However,its protective effects need to be further verified in animal tests.展开更多
Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditio...Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditional chemotherapy drugs do not achieve satisfactory therapeutic efficacy. The delivery of therapeutic compounds to the target site is a major challenge in the treatment of many diseases. Objective: This study aims to evaluate activated charcoal nanoparticles as a drug delivery system for anticancer agents (Sorafenib and Doxorubicin) in Hepatocellular Cancer Stem Cells. Method: The percent efficiency of entrapment (% EE) of the doxorubicin and sorafenib entrapped onto the activated charcoal was obtained by determining the free doxorubicin and sorafenib concentration in the supernatant-prepared solutions. Then the characterizations of nanoparticles were formed by determination of the particle size distribution, zeta potential, and polydispersity index (PDI). The anticancer activity of activated Charcoal, Doxorubicin-ACNP, sorafenib-ACNP, free doxorubicin, and free sorafenib solutions was measured based on cell viability percentage in HepG2 cell lines (ATCC-CCL 75). In vitro RBC’s toxicity of Doxorubicin/sorafenib loaded charcoal was estimated by hemolysis percentage. Results: The synthesized Doxorubicin-ACNP and Sorafenib-ACNP were evaluated and their physiochemical properties were also examined. Essentially, the percent Efficiency of Entrapment (EE %) was found to be 87.5% and 82.66% for Doxorubicin-ACNP and Sorafenib-ACNP, respectively. The loading capacity was 34.78% and 24.31% for Doxorubicin-ACNP and Sorafenib-ACNP. Using the Dynamic Light scattering [DLS] for the determination of the hydrodynamic size and surface zeta potential, a narrow sample size distribution was obtained of (18, 68, and 190 nm for charcoal, 105, 255, and 712 nm for doxorubicin, and 91, 295, and 955 nm for sorafenib), respectively. A surface charge of −13.2, −15.6 and −17 was obtained for charcoal, doxorubicin/charcoal, and sorafenib/charcoal nanoparticles. The cytotoxic activity of Doxorubicin-ACNP and Sorafenib-ACNP was evaluated in-vitro against HepG2 cell lines and it was observed that Drug loaded ACNP improved anticancer activity when compared to Doxorubicin or Sorafenib alone. Moreover, testing the toxicity potential of DOX-ACNP and Sorafenib-ACNP showed a significant reduction in the hemolysis of red blood cells when compared to Doxorubicin and Sorafenib alone. Conclusion: In conclusion, it is notable to state that this study is regarded as the first to investigate the use of Activated charcoal for the loading of Doxorubicin and Sorafenib for further use in the arena of hepatocellular carcinoma. Doxorubicin-ACNP and Sorafenib-ACNP showed noteworthy anticancer activity along with a reduced potential of RBCs hemolysis rendering it as an efficacious carrier with a low toxicity potential.展开更多
Aluminum alloys are the potential materials in the automobile and aerospace sectors due to their lower density,easy forming and excellent corrosion resistance.The demand of high strength-to-weight ratio materials in s...Aluminum alloys are the potential materials in the automobile and aerospace sectors due to their lower density,easy forming and excellent corrosion resistance.The demand of high strength-to-weight ratio materials in structural applications needs the engineering industries to seek aluminum alloy with new versions of hard and brittle ceramic particles.The microstructure,hardness,wear and corrosion behaviors of AA7075 composites with 2.5wt.%and 5wt.%TiC particles were studied.Microscopic analysis is evident that the transformation of the strong dendritic morphology to non-dendritic morphology on the incorporation of TiC into AA7075.Furthermore,the precipitation of the second-phase compounds such as Al_(2)CuMg,Al_(2)Cu andFe-rich Al_6(Cu,Fe)/Al_(7)Cu_(2)Fe)is promoted by TiC particles at inter-and intra-dendritic regions.Accordingly,the hardness of composites is improved by grain boundary strengthening and particulate strengthening mechanisms.Both coefficient of friction and wear rate have an inverse relation with TiC concentration.The base alloy without TiC shows adhesive-type wear-induced deformation due to the formation of an oxide film,while composite samples exhibit a mechanically mixed layer and abrasive-type wear behavior.Composite samples shows a higher corrosion rate due to the presence of numerous precipitates which promote pitting corrosion.展开更多
Considering their affordability and high strength-to-weight ratio,lightweight aluminium alloys are the subject of intensive research aimed at improving their properties for use in the aerospace industry.This research ...Considering their affordability and high strength-to-weight ratio,lightweight aluminium alloys are the subject of intensive research aimed at improving their properties for use in the aerospace industry.This research effort aims to develop novel hybrid composites based on AA 2014 alloy through the use of liquid metallurgy stir casting to reinforce dual ceramic particles of Zirconium Diboride(ZrB_(2))and Boron Carbide(B4C).The weight percentage(wt%)of ZrB_(2) was varied(0,5,10,and 15),while a constant 5 wt%of B4C was maintained during this fabrication.The as-cast samples have been assessed using an Optical Microscope(OM)and a Scanning Electron Microscope(SEM)with Energy Dispersive Spectroscopy(EDS).The properties such as hardness,tensile strength,and wear characteristics of stir cast specimens were assessed to examine the impact of varying weight percentages of reinforcements in AA 2014 alloy.In particular,dry sliding wear behaviour was evaluated considering varied loads using a pin-on-disc tribotester.As the weight%of ZrB_(2) grew and B4C was incorporated,hybrid composites showed higher hardness,tensile strength,and wear resistance.Notably,the incorporation of a cumulative reinforcement consisting of 15 wt%ZrB_(2) and 5 wt%B4C resulted in a significant 31.86%increase in hardness and a 44.1%increase in tensile strength compared to AA 2014 alloy.In addition,it has been detected that wear resistance of hybrid composite pin(containing 20 wt%cumulative reinforcement)is higher than that of other stir cast wear test pins during the whole range of applied loads.Fractured surfaces of tensile specimens showed ductile fracture in the AA 2014 matrix and mixed mode for hybrid composites.Worn surfaces obtained employing higher applied load indicated abrasive wear with little plastic deformation for hybrid composites and dominant adhesive wear for matrix alloy.Hence,the superior mechanical and tribological performance of hybrid composites can be attributed to dual reinforcement particles being dispersed well and the effective transmission of load at this specific composition.展开更多
The AA5052 aluminum alloy is widely used in automobile and aerospace manufacturing,and with the development of light-weight alloys,it is required that these materials exhibit better mechanical properties.Previous stud...The AA5052 aluminum alloy is widely used in automobile and aerospace manufacturing,and with the development of light-weight alloys,it is required that these materials exhibit better mechanical properties.Previous studies have demonstrated that the addition of Sc to aluminum alloys can improve both the microstructure and properties of the alloys.In this study,the effect of Sc on the Fe-rich phase and properties of the AA5052 aluminum alloy was studied by adding 0%,0.05%,0.2%,and 0.3%Sc.The results show that with the increase of Sc,the coarse needle-like Fe-rich phase gradually transforms into Chinese-script and then nearly spherical particles,reduce the size of Fe-rich phase,and refine the grain with increase of high angle grain boundaries(HAGBs).These microstructure changes enhance the strength of the AA5052 alloy through Sc addition.The ductility of the alloy is obviously improved because the addition of a lower amount of Sc changes the morphology of Fe-rich phase from needle-like into a Chinese-script,and it is subsequently reduced as a result of significant increase in HAGBs with increasing Sc content.展开更多
TA1 P-Ti/AA6061 composite plate was produced by oxidizing the surface of the titanium plate and adopting a cold roll bonding process.The results revealed that the oxide film(Ti6O)prepared on the surface of TA1 pure ti...TA1 P-Ti/AA6061 composite plate was produced by oxidizing the surface of the titanium plate and adopting a cold roll bonding process.The results revealed that the oxide film(Ti6O)prepared on the surface of TA1 pure titanium was easy to crack during the cold roll bonding,thereby promoting the formation of an effective mechanical interlock at the interface,which can effectively reduce the minimum reduction rate of the composite plates produced by cold rolling of titanium and aluminium plates.Moreover,the composite plate subjected to oxidation treatment exhibited high shear strength,particularly at a 43%reduction rate,achieving a commendable value of 117 MPa.Based on oxidation treatment and different reduction rates,the annealed composite plates at temperatures of 400,450,and 500°C displayed favorable resistance to interface delamination,highlighting their remarkable strength-plasticity compatibility as evidenced by a maximum elongation of 31.845%.展开更多
基金supported by the Natural Science Foundation of Hainan Province High-level Talent Project(grant number 820RC644)Innovative Research Projects for Postgraduate Students at Hainan Medical University(grant number HYYS2022B08).
文摘Objective:To explore whether thrombopoietin can exert a protective effect against doxorubicin-induced cardiotoxicity by modulating the sirtuin 1(SIRT1)signaling pathway.Methods:H9c2 cell viability was determined by CCK-8 and cardiomyocyte apoptosis was detected by TUNEL assay.The protein expressions of SIRT1 and p38 MAPK were measured by Western blot.RT-qPCR was also used to determine SIRT1 mRNA expression.In addition,intracellular reactive oxygen species levels and antioxidant enzyme activities were evaluated.Results:Thrombopoietin treatment reversed doxorubicin-induced decline in H9c2 cell viability.It also increased SIRT1 and decreased p-p38 MAPK protein expressions.In addition,thrombopoietin significantly attenuated doxorubicin-induced apoptosis and oxidative stress,and enhanced antioxidant enzyme activities.However,silencing SIRT1 abrogated the protective effects of thrombopoietin,as evidenced by reduced cell viability and increased oxidative stress and reactive oxygen species levels.Conclusions:Thrombopoietin alleviates doxorubicin-induced cardiomyocyte injury by reducing oxidative stress and apoptosis via the SIRT1/p38 MAPK pathway.However,its protective effects need to be further verified in animal tests.
文摘Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditional chemotherapy drugs do not achieve satisfactory therapeutic efficacy. The delivery of therapeutic compounds to the target site is a major challenge in the treatment of many diseases. Objective: This study aims to evaluate activated charcoal nanoparticles as a drug delivery system for anticancer agents (Sorafenib and Doxorubicin) in Hepatocellular Cancer Stem Cells. Method: The percent efficiency of entrapment (% EE) of the doxorubicin and sorafenib entrapped onto the activated charcoal was obtained by determining the free doxorubicin and sorafenib concentration in the supernatant-prepared solutions. Then the characterizations of nanoparticles were formed by determination of the particle size distribution, zeta potential, and polydispersity index (PDI). The anticancer activity of activated Charcoal, Doxorubicin-ACNP, sorafenib-ACNP, free doxorubicin, and free sorafenib solutions was measured based on cell viability percentage in HepG2 cell lines (ATCC-CCL 75). In vitro RBC’s toxicity of Doxorubicin/sorafenib loaded charcoal was estimated by hemolysis percentage. Results: The synthesized Doxorubicin-ACNP and Sorafenib-ACNP were evaluated and their physiochemical properties were also examined. Essentially, the percent Efficiency of Entrapment (EE %) was found to be 87.5% and 82.66% for Doxorubicin-ACNP and Sorafenib-ACNP, respectively. The loading capacity was 34.78% and 24.31% for Doxorubicin-ACNP and Sorafenib-ACNP. Using the Dynamic Light scattering [DLS] for the determination of the hydrodynamic size and surface zeta potential, a narrow sample size distribution was obtained of (18, 68, and 190 nm for charcoal, 105, 255, and 712 nm for doxorubicin, and 91, 295, and 955 nm for sorafenib), respectively. A surface charge of −13.2, −15.6 and −17 was obtained for charcoal, doxorubicin/charcoal, and sorafenib/charcoal nanoparticles. The cytotoxic activity of Doxorubicin-ACNP and Sorafenib-ACNP was evaluated in-vitro against HepG2 cell lines and it was observed that Drug loaded ACNP improved anticancer activity when compared to Doxorubicin or Sorafenib alone. Moreover, testing the toxicity potential of DOX-ACNP and Sorafenib-ACNP showed a significant reduction in the hemolysis of red blood cells when compared to Doxorubicin and Sorafenib alone. Conclusion: In conclusion, it is notable to state that this study is regarded as the first to investigate the use of Activated charcoal for the loading of Doxorubicin and Sorafenib for further use in the arena of hepatocellular carcinoma. Doxorubicin-ACNP and Sorafenib-ACNP showed noteworthy anticancer activity along with a reduced potential of RBCs hemolysis rendering it as an efficacious carrier with a low toxicity potential.
文摘Aluminum alloys are the potential materials in the automobile and aerospace sectors due to their lower density,easy forming and excellent corrosion resistance.The demand of high strength-to-weight ratio materials in structural applications needs the engineering industries to seek aluminum alloy with new versions of hard and brittle ceramic particles.The microstructure,hardness,wear and corrosion behaviors of AA7075 composites with 2.5wt.%and 5wt.%TiC particles were studied.Microscopic analysis is evident that the transformation of the strong dendritic morphology to non-dendritic morphology on the incorporation of TiC into AA7075.Furthermore,the precipitation of the second-phase compounds such as Al_(2)CuMg,Al_(2)Cu andFe-rich Al_6(Cu,Fe)/Al_(7)Cu_(2)Fe)is promoted by TiC particles at inter-and intra-dendritic regions.Accordingly,the hardness of composites is improved by grain boundary strengthening and particulate strengthening mechanisms.Both coefficient of friction and wear rate have an inverse relation with TiC concentration.The base alloy without TiC shows adhesive-type wear-induced deformation due to the formation of an oxide film,while composite samples exhibit a mechanically mixed layer and abrasive-type wear behavior.Composite samples shows a higher corrosion rate due to the presence of numerous precipitates which promote pitting corrosion.
文摘Considering their affordability and high strength-to-weight ratio,lightweight aluminium alloys are the subject of intensive research aimed at improving their properties for use in the aerospace industry.This research effort aims to develop novel hybrid composites based on AA 2014 alloy through the use of liquid metallurgy stir casting to reinforce dual ceramic particles of Zirconium Diboride(ZrB_(2))and Boron Carbide(B4C).The weight percentage(wt%)of ZrB_(2) was varied(0,5,10,and 15),while a constant 5 wt%of B4C was maintained during this fabrication.The as-cast samples have been assessed using an Optical Microscope(OM)and a Scanning Electron Microscope(SEM)with Energy Dispersive Spectroscopy(EDS).The properties such as hardness,tensile strength,and wear characteristics of stir cast specimens were assessed to examine the impact of varying weight percentages of reinforcements in AA 2014 alloy.In particular,dry sliding wear behaviour was evaluated considering varied loads using a pin-on-disc tribotester.As the weight%of ZrB_(2) grew and B4C was incorporated,hybrid composites showed higher hardness,tensile strength,and wear resistance.Notably,the incorporation of a cumulative reinforcement consisting of 15 wt%ZrB_(2) and 5 wt%B4C resulted in a significant 31.86%increase in hardness and a 44.1%increase in tensile strength compared to AA 2014 alloy.In addition,it has been detected that wear resistance of hybrid composite pin(containing 20 wt%cumulative reinforcement)is higher than that of other stir cast wear test pins during the whole range of applied loads.Fractured surfaces of tensile specimens showed ductile fracture in the AA 2014 matrix and mixed mode for hybrid composites.Worn surfaces obtained employing higher applied load indicated abrasive wear with little plastic deformation for hybrid composites and dominant adhesive wear for matrix alloy.Hence,the superior mechanical and tribological performance of hybrid composites can be attributed to dual reinforcement particles being dispersed well and the effective transmission of load at this specific composition.
基金supported by the Key Research&Development Program of Yunnan Province(Grant numbers 202103AA080017,202203AE140011).
文摘The AA5052 aluminum alloy is widely used in automobile and aerospace manufacturing,and with the development of light-weight alloys,it is required that these materials exhibit better mechanical properties.Previous studies have demonstrated that the addition of Sc to aluminum alloys can improve both the microstructure and properties of the alloys.In this study,the effect of Sc on the Fe-rich phase and properties of the AA5052 aluminum alloy was studied by adding 0%,0.05%,0.2%,and 0.3%Sc.The results show that with the increase of Sc,the coarse needle-like Fe-rich phase gradually transforms into Chinese-script and then nearly spherical particles,reduce the size of Fe-rich phase,and refine the grain with increase of high angle grain boundaries(HAGBs).These microstructure changes enhance the strength of the AA5052 alloy through Sc addition.The ductility of the alloy is obviously improved because the addition of a lower amount of Sc changes the morphology of Fe-rich phase from needle-like into a Chinese-script,and it is subsequently reduced as a result of significant increase in HAGBs with increasing Sc content.
基金supports from the National Natural Science Foundation of China(Nos.52075472,52004242)the National Key Research and Development Program of China(No.2018YFA0707300)the Natural Science Foundation of Hebei Province,China(No.E2020203001)。
文摘TA1 P-Ti/AA6061 composite plate was produced by oxidizing the surface of the titanium plate and adopting a cold roll bonding process.The results revealed that the oxide film(Ti6O)prepared on the surface of TA1 pure titanium was easy to crack during the cold roll bonding,thereby promoting the formation of an effective mechanical interlock at the interface,which can effectively reduce the minimum reduction rate of the composite plates produced by cold rolling of titanium and aluminium plates.Moreover,the composite plate subjected to oxidation treatment exhibited high shear strength,particularly at a 43%reduction rate,achieving a commendable value of 117 MPa.Based on oxidation treatment and different reduction rates,the annealed composite plates at temperatures of 400,450,and 500°C displayed favorable resistance to interface delamination,highlighting their remarkable strength-plasticity compatibility as evidenced by a maximum elongation of 31.845%.
