Nowadays,doctors and nutritionists recommend individuals incorporate selenium-rich foods such as nuts,cereals,and mushrooms into their regular diet to maintain fitness and overall health.Selenium nanoparticles(SeNPs)e...Nowadays,doctors and nutritionists recommend individuals incorporate selenium-rich foods such as nuts,cereals,and mushrooms into their regular diet to maintain fitness and overall health.Selenium nanoparticles(SeNPs)exhibit strong chemopreventive capabilities.The anticipations for SeNPs with enhanced and tunable bioactive activities have led to a keen interest in phytofabrication.In this study,the aqueous extract of Clerodendron phlomidis plant leaves was utilized for the synthesis of SeNPs.In traditional Indian medicine,this plant extract is recognized as a significant anti-diabetic agent.The flavonoids tetrahydroxylflavone,7-hydroxyflavanone,and 6,4’-dimethyl-7-acetoxy-scutellarein present in this plant leaf extract demonstrate excellent anticancer activity.These secondary metabolites exhibit the ability to reduce sodium selenite into SeNPs.At a concentration of 13μg/mL,the synthesized SeNPs effectively inhibited the proliferation of the HepG2 cell line.The results suggest that the SeNPs possess promising anti-cancer potential against liver cancer and can be considered as a therapeutic agent for liver cancer treatment.Additionally,the cell cycle arrest induced by SeNPs was further confirmed by the fluorescence-activated cell sorting(FACS)method,indicating that SeNPs could efficiently differentiate cancer cells from normal cells.Notably,it showed a significant improvement in diethylnitrosamine(DEN)-induced Swiss Wistar rat groups.This scientific investigation highlights the high anti-cancer potential of SeNPs,positioning them as a promising therapeutic agent for liver cancer treatment.展开更多
The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the brain.Among the various strategies that have been studied to circum...The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the brain.Among the various strategies that have been studied to circumvent this challenge,the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results.In addition,the encapsulation of the drugs in lipid-based nanocarriers,such as solid lipid nanoparticles(SLNs),nanostructured lipid carriers(NLCs)or nanoemulsions(NEs),can improve nose-to-brain transport by increasing the bioavailability and site-specifc delivery.This review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers(SLNs,NLCs and NEs)for nose-to-brain delivery.Based on the literature available from the past two years,we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration.The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried out.Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear,it appears that the intranasal route together with the use of NLCs,SLNs or NEs is advantageous for targeting drugs to the brain.These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs,so they are expected to be approved by regulatory authorities in the coming years.展开更多
Cerium oxide nanoparticles(CNPs)possess a great potential as therapeutic agents due to their ability to self-regenerate by reversibly switching between two valences+3 and+4.This article reviews recent articles dealing...Cerium oxide nanoparticles(CNPs)possess a great potential as therapeutic agents due to their ability to self-regenerate by reversibly switching between two valences+3 and+4.This article reviews recent articles dealing with in vivo studies of CNPs towards Alzheimer’s disease,obesity,liver inflammation,cancer,sepsis,amyotrophic lateral sclerosis,acute kidney injury,radiation-induced tissue damage,hepatic ischemia reperfusion injury,retinal diseases and constipation.In vivo anti-cancer studies revealed the effectiveness of CNPs to reduce tumor growth and angiogenesis in melanoma,ovarian,breast and retinoblastoma cancer cell-induced mice,with their conjugation with folic acid,doxorubicin,CPM,or CXC receptor-4 antagonist ligand eliciting higher efficiency.After conjugation with triphenylphosphonium or magnetite nanoparticles,CNPs were shown to combat Alzheimer’s disease by reducing amyloid-β,glial fibrillary acidic protein,inflammatory and oxidative stress markers in mice.By improving muscle function and longevity,the citrate/EDTA-stabilized CNPs could ameliorate amyotrophic lateral sclerosis.Also,they could effectively reduce obesity in mice by scavenging ROS and reducing adipogenesis,triglyceride synthesis,GAPDH enzyme activity,leptin and insulin levels.In CCl4-induced rats,stress signaling pathways due to inflammatory cytokines,liver enzymes,oxidative and endoplasmic reticulum messengers could be attenuated by CNPs.Commercial CNPs showed protective effects on rats with hepatic ischemia reperfusion and peritonitis-induced hepatic/cardiac injuries by decreasing oxidative stress and hepatic/cardiac inflammation.The same CNPs could improve kidney function by diminishing renal superoxide,hyperglycemia and tubular damage in peritonitis-induced acute kidney injury in rats.Radiation-induced lung and testicular tissue damage could be alleviated in mice,with the former showing improvement in pulmonary distress and bronchoconstriction and the latter exhibiting restoration in spermatogenesis rate and spermatid/spermatocyte number.Through enhancement of gastrointestinal motility,the CNPs could alleviate constipation in both young and old rats.They could also protect rat from light-induced retinal damage by slowing down neurodegenerative process and microglial activation.展开更多
In this study,diltiazem hydrochloride(DTZ)pellets were prepared successfully by extrusionespheronization method.Then methacrylic acid and ethylcellulose coating formulations were employed to make the DTZ pellets sus...In this study,diltiazem hydrochloride(DTZ)pellets were prepared successfully by extrusionespheronization method.Then methacrylic acid and ethylcellulose coating formulations were employed to make the DTZ pellets sustained release.The pellets with different coatings were investigated by in vitro dissolution tests.At last,the pellets with the best coating copolymer were subjected to pharmacokinetic studies in beagle dogs.The dissolution profiles of pellets coated with EudragitNE30D were similar to Herbesser,one of the marketed sustained release capsules.In the bioavailability study,the principal pharmacokinetic parameters of self-made pellets and the marketed ones were comparable;the relative bioavailability of DTZ sustained release capsules compared with Herbesserwas 98.536.4%.All the data indicated self-made sustained pellets could prolong the release of DTZ,decrease the fluctuation of drug level in vivo,and increase the compliance of patients.展开更多
In this study, a rat model of transient focal cerebral ischemia was established by performing 100 minutes of middle cerebral artery occlusion, and an in vitro model of experimental oxygen-glucose deprivation using cul...In this study, a rat model of transient focal cerebral ischemia was established by performing 100 minutes of middle cerebral artery occlusion, and an in vitro model of experimental oxygen-glucose deprivation using cultured rat cortical neurons was established. Proprotein convertase 2 activity gradually decreased in the ischemic cortex with increasing duration of reperfusion. In cultured rat cortical neurons, the number of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling-positive neurons significantly increased and proprotein convertase 2 activity also decreased gradually with increasing duration of oxygen-glucose deprivation. These experimental findings indicate that proprotein convertase 2 activity decreases in ischemic rat cortex after reperfusion, as well as in cultured rat cortical neurons after oxygen-glucose deprivation. These changes in enzyme activity may play an important pathological role in brain injury.展开更多
Objective:To study the mechanism of kaempferol in the intervention of knee osteoarthritis(KOA)in mice by inhibiting cartilage apoptosis.Methods:Firstly,the target genes of kaempferol were retrieved via TCMSP,and the g...Objective:To study the mechanism of kaempferol in the intervention of knee osteoarthritis(KOA)in mice by inhibiting cartilage apoptosis.Methods:Firstly,the target genes of kaempferol were retrieved via TCMSP,and the genes related to KOA were obtained by GeneCards,OMIM,PharmGKB,TTD,and Drugbank databases.Then GO enrichment analysis and KEGG signaling pathway analysis were also performed.Subsequently,18 male C57 mice were randomly divided into the sham operation group,the model group,and the kaempferol group(50 mg/kg).Except for the sham operation group,the KOA mouse model was induced by destabilization of medial meniscus surgery.The sham operation group and model group were given the same amount of normal saline daily for 8 weeks while the kaempferol group was given 50 mg/kg kaempferol intragastrically.Results:A total of 63 targets of kaempferol were found that included 35 common target genes with KOA.GO and KEGG analyses showed that biological processes such as extrinsic apoptotic signaling pathway and response to oxidative stress,as well as signaling pathways such as cell apoptosis and regulation of TNF were closely related to common target genes.Molecular docking results also showed kaempferol has good binding properties with predicted targets Bcl-2,BAX,and CASP3.Compared with the model group,the pathological changes of cartilage in the kaempferol group were significantly reduced,OARSI scores were significantly decreased(P<0.001),and cartilage area was increased(P<0.01).In addition,Western blot analysis showed that kaempferol significantly decreased the protein expression of BAX and CASP3(P<0.01,P<0.05),and increased the protein expression of BCL-2(P<0.05).Conclusion:The treatment of KOA with kaempferol has the characteristics of multi-target and multi-pathway,and the mechanism may be related to the regulation of key genes such as Bcl-2,BAX,and CASP3 to inhibit cartilage apoptosis.展开更多
Laser surface texturing is a versatile approach for manufacturing implants with suitable surfaces for os-seointegration.This work explores the use of laser to fabricate NiTi textured implants,testing two dif-ferent gr...Laser surface texturing is a versatile approach for manufacturing implants with suitable surfaces for os-seointegration.This work explores the use of laser to fabricate NiTi textured implants,testing two dif-ferent groove-based designs.Their performance was evaluated in vivo through implantation in Sprague Dawley rats’femur,being then analyzed after 4 and 12 weeks of implantation.Push-out experiments and histological characterization allowed to assess bone-implant bond and osseointegration and to compare the laser textured solutions with non-textured NiTi.Histology showed that,at 4 weeks of implantation,mainly immature woven bone was present whilst at 12 weeks a more mature bone had developed.Con-sidering the largest implantation time(12 weeks),results showed extraction forces considerably higher for textured implants(G2 and G3).Moreover,when comparing G2 and G3,it was found that G2(having the highest textured surface area)displayed the maximum extraction force among all groups,with an increase of 212%when compared to non-textured implants(G1).These results prove that the design and manufacturing technology are effective to promote an im-proved bone-implant bond,aiming the development of orthopedic implants.展开更多
The macrophages mediated biodegradation of two biomaterials, collagen / hydroxylapatite (CHA) and beta-tricalcium phosphate ceramics (TCP), was studied in 24 male Kunming mice and 20 male C57BL / 6 mice with histopath...The macrophages mediated biodegradation of two biomaterials, collagen / hydroxylapatite (CHA) and beta-tricalcium phosphate ceramics (TCP), was studied in 24 male Kunming mice and 20 male C57BL / 6 mice with histopathologic, histochemical and ultrastructural observation. It was demonstrated that macrophages infiltrated after CHA, TCP were implanted. The macrophages could be differentiated from fibroblasts and the other infiltrated cells for special cellular profile and strong acid phosphatase activity. Morphologically, monocyte macrophages and infused multinuclear giant cell degraded CHA and TCP by phagocytosis and extracellular resorption. The carbonic anhydrase activity of macrophages was demonstrated by histochemical technique. It suggested that macrophages secreted H+ and accomplished the decalcification of calcium phosphate compound of CHA and TCP. We conclude that macrophages are the main mediating cells which degraded CHA and TCP intracellularly and extracellularly.展开更多
Size characterization of silver nanoparticles with biomolecule corona(AgNP@BCs) and mass quantification of various silver species in organisms are essential for understanding the in vivo transformation of Ag NPs. He...Size characterization of silver nanoparticles with biomolecule corona(AgNP@BCs) and mass quantification of various silver species in organisms are essential for understanding the in vivo transformation of Ag NPs. Herein, we report a versatile method that allows simultaneous determination of the size of AgNP@BCs and mass concentration of various silver species in rat liver. Both particulate and ionic silver were extracted in their original forms from the organs by alkaline digestion, and analyzed by size exclusion chromatography combined with inductively coupled plasma mass spectrometry(SEC-ICP-MS). While the silver mass concentrations were quantified by ICP-MS with a detection limit of 0.1 μg/g, the effective diameter of AgNP@BCs was determined based on the retention time in SEC separation with size discrimination of 0.6-3.3 nm. More importantly, we found that the BC thickness of AgNP@BCs is core size independent, and a linear correlation was found between the effective diameter and core diameter of AgNP@BCs in extracted tissues, which was used to calibrate the core diameter with standard deviations in the range of 0.2-1.1 nm. The utility of this strategy was demonstrated through application to rat livers in vivo. Our method is powerful for investigating the transformation mechanism of Ag NPs in vivo.展开更多
Overexpression of ABCG2 transporter in cancer cells has been linked to the development of multidrug resistance(MDR), an obstacle to cancer therapy. Our recent study uncovered that the MET inhibitor,tepotinib, is a pot...Overexpression of ABCG2 transporter in cancer cells has been linked to the development of multidrug resistance(MDR), an obstacle to cancer therapy. Our recent study uncovered that the MET inhibitor,tepotinib, is a potent reversal agent for ABCB1-mediated MDR. In the present study, we reported for the first time that the MET inhibitor tepotinib can also reverse ABCG2-mediated MDR in vitro and in vivo by directly binding to the drug-binding site of ABCG2 and reversibly inhibiting ABCG2 drug efflux activity, therefore enhancing the cytotoxicity of substrate drugs in drug-resistant cancer cells. Furthermore, the ABCB1/ABCG2 double-transfected cell model and ABCG2 gene knockout cell model demonstrated that tepotinib specifically inhibits the two MDR transporters. In mice bearing drug-resistant tumors, tepotinib increased the intratumoral accumulation of ABCG2 substrate drug topotecan and enhanced its antitumor effect. Therefore, our study provides a new potential of repositioning tepotinib as an ABCG2 inhibitor and combining tepotinib with substrate drugs to antagonize ABCG2-mediated MDR.展开更多
Diabetic nephropathy is one of the main causes of renal end-stage disease. The pathogenesis of diabetic nephropathy is complex. The current treatment is only for a particular cause without multi-target therapeutic dru...Diabetic nephropathy is one of the main causes of renal end-stage disease. The pathogenesis of diabetic nephropathy is complex. The current treatment is only for a particular cause without multi-target therapeutic drugs. Chinese medicine is a great treasure with multi-component complex drugs interacting with multiple targets and functions. This paper reviewed the protective effect of Chinese medicine for treating diabetic nephropathy in clinical studies, in vivo studies, and in vitro studies. The possible mechanisms, the major compounds and active crude drugs were also summarized. It was shown that Chinese medicine could not only relieve several symptoms and improve the quality of life, but also reduce the levels of proteinuria and kidney damage, and further improve renal function via multiple pathways based on the whole human system. Moreover, there were no reports of severe adverse reactions during the treatment.展开更多
文摘Nowadays,doctors and nutritionists recommend individuals incorporate selenium-rich foods such as nuts,cereals,and mushrooms into their regular diet to maintain fitness and overall health.Selenium nanoparticles(SeNPs)exhibit strong chemopreventive capabilities.The anticipations for SeNPs with enhanced and tunable bioactive activities have led to a keen interest in phytofabrication.In this study,the aqueous extract of Clerodendron phlomidis plant leaves was utilized for the synthesis of SeNPs.In traditional Indian medicine,this plant extract is recognized as a significant anti-diabetic agent.The flavonoids tetrahydroxylflavone,7-hydroxyflavanone,and 6,4’-dimethyl-7-acetoxy-scutellarein present in this plant leaf extract demonstrate excellent anticancer activity.These secondary metabolites exhibit the ability to reduce sodium selenite into SeNPs.At a concentration of 13μg/mL,the synthesized SeNPs effectively inhibited the proliferation of the HepG2 cell line.The results suggest that the SeNPs possess promising anti-cancer potential against liver cancer and can be considered as a therapeutic agent for liver cancer treatment.Additionally,the cell cycle arrest induced by SeNPs was further confirmed by the fluorescence-activated cell sorting(FACS)method,indicating that SeNPs could efficiently differentiate cancer cells from normal cells.Notably,it showed a significant improvement in diethylnitrosamine(DEN)-induced Swiss Wistar rat groups.This scientific investigation highlights the high anti-cancer potential of SeNPs,positioning them as a promising therapeutic agent for liver cancer treatment.
基金supported by Fundacao para a Ciência e a Tecnologia(FCT)(SFRH/136177/2018,Portugal)the Applied Molecular Biosciences Unit-UCIBIO which is fnanced by national funds from FCT(UIDP/04378/2020 and UIDB/04378/2020)。
文摘The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the brain.Among the various strategies that have been studied to circumvent this challenge,the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results.In addition,the encapsulation of the drugs in lipid-based nanocarriers,such as solid lipid nanoparticles(SLNs),nanostructured lipid carriers(NLCs)or nanoemulsions(NEs),can improve nose-to-brain transport by increasing the bioavailability and site-specifc delivery.This review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers(SLNs,NLCs and NEs)for nose-to-brain delivery.Based on the literature available from the past two years,we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration.The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried out.Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear,it appears that the intranasal route together with the use of NLCs,SLNs or NEs is advantageous for targeting drugs to the brain.These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs,so they are expected to be approved by regulatory authorities in the coming years.
文摘Cerium oxide nanoparticles(CNPs)possess a great potential as therapeutic agents due to their ability to self-regenerate by reversibly switching between two valences+3 and+4.This article reviews recent articles dealing with in vivo studies of CNPs towards Alzheimer’s disease,obesity,liver inflammation,cancer,sepsis,amyotrophic lateral sclerosis,acute kidney injury,radiation-induced tissue damage,hepatic ischemia reperfusion injury,retinal diseases and constipation.In vivo anti-cancer studies revealed the effectiveness of CNPs to reduce tumor growth and angiogenesis in melanoma,ovarian,breast and retinoblastoma cancer cell-induced mice,with their conjugation with folic acid,doxorubicin,CPM,or CXC receptor-4 antagonist ligand eliciting higher efficiency.After conjugation with triphenylphosphonium or magnetite nanoparticles,CNPs were shown to combat Alzheimer’s disease by reducing amyloid-β,glial fibrillary acidic protein,inflammatory and oxidative stress markers in mice.By improving muscle function and longevity,the citrate/EDTA-stabilized CNPs could ameliorate amyotrophic lateral sclerosis.Also,they could effectively reduce obesity in mice by scavenging ROS and reducing adipogenesis,triglyceride synthesis,GAPDH enzyme activity,leptin and insulin levels.In CCl4-induced rats,stress signaling pathways due to inflammatory cytokines,liver enzymes,oxidative and endoplasmic reticulum messengers could be attenuated by CNPs.Commercial CNPs showed protective effects on rats with hepatic ischemia reperfusion and peritonitis-induced hepatic/cardiac injuries by decreasing oxidative stress and hepatic/cardiac inflammation.The same CNPs could improve kidney function by diminishing renal superoxide,hyperglycemia and tubular damage in peritonitis-induced acute kidney injury in rats.Radiation-induced lung and testicular tissue damage could be alleviated in mice,with the former showing improvement in pulmonary distress and bronchoconstriction and the latter exhibiting restoration in spermatogenesis rate and spermatid/spermatocyte number.Through enhancement of gastrointestinal motility,the CNPs could alleviate constipation in both young and old rats.They could also protect rat from light-induced retinal damage by slowing down neurodegenerative process and microglial activation.
文摘In this study,diltiazem hydrochloride(DTZ)pellets were prepared successfully by extrusionespheronization method.Then methacrylic acid and ethylcellulose coating formulations were employed to make the DTZ pellets sustained release.The pellets with different coatings were investigated by in vitro dissolution tests.At last,the pellets with the best coating copolymer were subjected to pharmacokinetic studies in beagle dogs.The dissolution profiles of pellets coated with EudragitNE30D were similar to Herbesser,one of the marketed sustained release capsules.In the bioavailability study,the principal pharmacokinetic parameters of self-made pellets and the marketed ones were comparable;the relative bioavailability of DTZ sustained release capsules compared with Herbesserwas 98.536.4%.All the data indicated self-made sustained pellets could prolong the release of DTZ,decrease the fluctuation of drug level in vivo,and increase the compliance of patients.
基金supported by the National Natural Science Foundation of China,No.81070999the foundation of Xi’an Jiaotong University,No.95,2009+2 种基金Foundation of the Second Affiliated Hospital of Xi’an Jiaotong University,No.RC(GG)201109the US National Institutes of Health,No.NS046560the American Heart Association,No.0450142Z
文摘In this study, a rat model of transient focal cerebral ischemia was established by performing 100 minutes of middle cerebral artery occlusion, and an in vitro model of experimental oxygen-glucose deprivation using cultured rat cortical neurons was established. Proprotein convertase 2 activity gradually decreased in the ischemic cortex with increasing duration of reperfusion. In cultured rat cortical neurons, the number of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling-positive neurons significantly increased and proprotein convertase 2 activity also decreased gradually with increasing duration of oxygen-glucose deprivation. These experimental findings indicate that proprotein convertase 2 activity decreases in ischemic rat cortex after reperfusion, as well as in cultured rat cortical neurons after oxygen-glucose deprivation. These changes in enzyme activity may play an important pathological role in brain injury.
基金This study was supported by the National Natural Science Foundation of China(No.81874476)National Key R&D Project(No.2018YFC2002500)+5 种基金Hunan Natural Science Foundation Project(2018JJ2303,2019JJ50462,2020JJ5422)Innovation Project of Hunan Science and Technology Department(No.2017SK50302)Project of Hunan Administration of Traditional Chinese Medicine(No.2015165)Hunan Health Commission Project(No.202104070364)Graduate Student Innovation Project of Hunan University of Chinese Medicine(No.2021CX71)Construction Project of First-Class Discipline of Traditional Chinese Medicine in Hunan University of Chinese Medicine(No.2021ZYX32)。
文摘Objective:To study the mechanism of kaempferol in the intervention of knee osteoarthritis(KOA)in mice by inhibiting cartilage apoptosis.Methods:Firstly,the target genes of kaempferol were retrieved via TCMSP,and the genes related to KOA were obtained by GeneCards,OMIM,PharmGKB,TTD,and Drugbank databases.Then GO enrichment analysis and KEGG signaling pathway analysis were also performed.Subsequently,18 male C57 mice were randomly divided into the sham operation group,the model group,and the kaempferol group(50 mg/kg).Except for the sham operation group,the KOA mouse model was induced by destabilization of medial meniscus surgery.The sham operation group and model group were given the same amount of normal saline daily for 8 weeks while the kaempferol group was given 50 mg/kg kaempferol intragastrically.Results:A total of 63 targets of kaempferol were found that included 35 common target genes with KOA.GO and KEGG analyses showed that biological processes such as extrinsic apoptotic signaling pathway and response to oxidative stress,as well as signaling pathways such as cell apoptosis and regulation of TNF were closely related to common target genes.Molecular docking results also showed kaempferol has good binding properties with predicted targets Bcl-2,BAX,and CASP3.Compared with the model group,the pathological changes of cartilage in the kaempferol group were significantly reduced,OARSI scores were significantly decreased(P<0.001),and cartilage area was increased(P<0.01).In addition,Western blot analysis showed that kaempferol significantly decreased the protein expression of BAX and CASP3(P<0.01,P<0.05),and increased the protein expression of BCL-2(P<0.05).Conclusion:The treatment of KOA with kaempferol has the characteristics of multi-target and multi-pathway,and the mechanism may be related to the regulation of key genes such as Bcl-2,BAX,and CASP3 to inhibit cartilage apoptosis.
基金supported by FCT through the grants (No. SFRH/BD/140191/2018)the project No. PTDC/EME-EME/1442/2020 (Add2Mech Bio)+2 种基金by the project No. PTDC/EME-EME/30498/2017 (Fun Imp)also funded by National funds, through the Foundation for Science and Technology (FCT) (project Nos. UIDB/50026/2020 and UIDP/50026/2020)supported by FCT national funds, under the national support to R&D units grant, through the reference projects (Nos. UIDB/04436/2020 and UIDP/04436/2020)
文摘Laser surface texturing is a versatile approach for manufacturing implants with suitable surfaces for os-seointegration.This work explores the use of laser to fabricate NiTi textured implants,testing two dif-ferent groove-based designs.Their performance was evaluated in vivo through implantation in Sprague Dawley rats’femur,being then analyzed after 4 and 12 weeks of implantation.Push-out experiments and histological characterization allowed to assess bone-implant bond and osseointegration and to compare the laser textured solutions with non-textured NiTi.Histology showed that,at 4 weeks of implantation,mainly immature woven bone was present whilst at 12 weeks a more mature bone had developed.Con-sidering the largest implantation time(12 weeks),results showed extraction forces considerably higher for textured implants(G2 and G3).Moreover,when comparing G2 and G3,it was found that G2(having the highest textured surface area)displayed the maximum extraction force among all groups,with an increase of 212%when compared to non-textured implants(G1).These results prove that the design and manufacturing technology are effective to promote an im-proved bone-implant bond,aiming the development of orthopedic implants.
文摘The macrophages mediated biodegradation of two biomaterials, collagen / hydroxylapatite (CHA) and beta-tricalcium phosphate ceramics (TCP), was studied in 24 male Kunming mice and 20 male C57BL / 6 mice with histopathologic, histochemical and ultrastructural observation. It was demonstrated that macrophages infiltrated after CHA, TCP were implanted. The macrophages could be differentiated from fibroblasts and the other infiltrated cells for special cellular profile and strong acid phosphatase activity. Morphologically, monocyte macrophages and infused multinuclear giant cell degraded CHA and TCP by phagocytosis and extracellular resorption. The carbonic anhydrase activity of macrophages was demonstrated by histochemical technique. It suggested that macrophages secreted H+ and accomplished the decalcification of calcium phosphate compound of CHA and TCP. We conclude that macrophages are the main mediating cells which degraded CHA and TCP intracellularly and extracellularly.
基金supported by the National Key Research and Development Program of China(No.2016YFA0203102)the National Natural Science Foundation of China(Nos.21337004,21620102008)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB14020101)
文摘Size characterization of silver nanoparticles with biomolecule corona(AgNP@BCs) and mass quantification of various silver species in organisms are essential for understanding the in vivo transformation of Ag NPs. Herein, we report a versatile method that allows simultaneous determination of the size of AgNP@BCs and mass concentration of various silver species in rat liver. Both particulate and ionic silver were extracted in their original forms from the organs by alkaline digestion, and analyzed by size exclusion chromatography combined with inductively coupled plasma mass spectrometry(SEC-ICP-MS). While the silver mass concentrations were quantified by ICP-MS with a detection limit of 0.1 μg/g, the effective diameter of AgNP@BCs was determined based on the retention time in SEC separation with size discrimination of 0.6-3.3 nm. More importantly, we found that the BC thickness of AgNP@BCs is core size independent, and a linear correlation was found between the effective diameter and core diameter of AgNP@BCs in extracted tissues, which was used to calibrate the core diameter with standard deviations in the range of 0.2-1.1 nm. The utility of this strategy was demonstrated through application to rat livers in vivo. Our method is powerful for investigating the transformation mechanism of Ag NPs in vivo.
基金supported by the Key Research and Development Program of Jiangsu Province (BE2020637,China)Wuxi double hundred young and middle-aged medical and health top-notch talent project (No.202014,China)。
文摘Overexpression of ABCG2 transporter in cancer cells has been linked to the development of multidrug resistance(MDR), an obstacle to cancer therapy. Our recent study uncovered that the MET inhibitor,tepotinib, is a potent reversal agent for ABCB1-mediated MDR. In the present study, we reported for the first time that the MET inhibitor tepotinib can also reverse ABCG2-mediated MDR in vitro and in vivo by directly binding to the drug-binding site of ABCG2 and reversibly inhibiting ABCG2 drug efflux activity, therefore enhancing the cytotoxicity of substrate drugs in drug-resistant cancer cells. Furthermore, the ABCB1/ABCG2 double-transfected cell model and ABCG2 gene knockout cell model demonstrated that tepotinib specifically inhibits the two MDR transporters. In mice bearing drug-resistant tumors, tepotinib increased the intratumoral accumulation of ABCG2 substrate drug topotecan and enhanced its antitumor effect. Therefore, our study provides a new potential of repositioning tepotinib as an ABCG2 inhibitor and combining tepotinib with substrate drugs to antagonize ABCG2-mediated MDR.
基金Supported by the Major Discipline Clinical Research Project of the China Academy of Chinese Medical Sciences(No. CACMS05Y026)"Eleventh Five-Year"National Science and Technology Support Project of China(No.2006BAI04A04-2-2)National Specific Purpose of Major New Drugs"Great Platform of Research and Development of Integral Traditional Chinese Medicine"(No.2009ZX09301-005)
文摘Diabetic nephropathy is one of the main causes of renal end-stage disease. The pathogenesis of diabetic nephropathy is complex. The current treatment is only for a particular cause without multi-target therapeutic drugs. Chinese medicine is a great treasure with multi-component complex drugs interacting with multiple targets and functions. This paper reviewed the protective effect of Chinese medicine for treating diabetic nephropathy in clinical studies, in vivo studies, and in vitro studies. The possible mechanisms, the major compounds and active crude drugs were also summarized. It was shown that Chinese medicine could not only relieve several symptoms and improve the quality of life, but also reduce the levels of proteinuria and kidney damage, and further improve renal function via multiple pathways based on the whole human system. Moreover, there were no reports of severe adverse reactions during the treatment.