Chronic diabetic wounds confront a significant medical challenge because of increasing prevalence and difficult-healing circumstances.It is vital to develop multifunctional hydrogel dressings,with well-designed morpho...Chronic diabetic wounds confront a significant medical challenge because of increasing prevalence and difficult-healing circumstances.It is vital to develop multifunctional hydrogel dressings,with well-designed morphology and structure to enhance flexibility and effectiveness in wound management.To achieve these,we propose a self-healing hydrogel dressing based on structural color microspheres for wound management.The microsphere comprised a photothermal-responsive inverse opal framework,which was constructed by hyaluronic acid methacryloyl,silk fibroin methacryloyl and black phosphorus quantum dots(BPQDs),and was further re-filled with a dynamic hydrogel.The dynamic hydrogel filler was formed by Knoevenagel condensation reaction between cyanoacetate and benzaldehyde-functionalized dextran(DEX-CA and DEX-BA).Notably,the composite microspheres can be applied arbitrarily,and they can adhere together upon near-infrared irradiation by leveraging the BPQDs-mediated photothermal effect and the thermoreversible stiffness change of dynamic hydrogel.Additionally,eumenitin and vascular endothelial growth factor were co-loaded in the microspheres and their release behavior can be regulated by the same mechanism.Moreover,effective monitoring of the drug release process can be achieved through visual color variations.The microsphere system has demonstrated desired capabilities of controllable drug release and efficient wound management.These characteristics suggest broad prospects for the proposed composite microspheres in clinical applications.展开更多
Objective:To investigate the renoprotective effects of luteolin on diabetes in rats.Methods:One week after administration of streptozotocin 55 mg/kg intraperitoneally,rats were given 25,50,and 75 mg/kg/day of luteolin...Objective:To investigate the renoprotective effects of luteolin on diabetes in rats.Methods:One week after administration of streptozotocin 55 mg/kg intraperitoneally,rats were given 25,50,and 75 mg/kg/day of luteolin orally for another eight weeks.At the end of the experiment,body weight,blood glucose level,biochemical parameters for renal function(serum creatinine,blood urea nitrogen,uric acid,serum albumin,and total protein),kidney histology,matrix metalloproteinase(MMP)-2,MMP-9,and histone deacetylase 2(HDAC-2)expression,and malondialdehyde,myeloperoxidase,and hydroxyproline content in renal tissue were evaluated.High glucose-induced damage using NRK-52E cell line was studied to evaluate cell viability and metalloenzyme expression.Additionally,in silico studies including docking and molecular dynamics simulations were conducted.Results:MMP-2,MMP-9,and HDAC-2 expressions were significantly increased in high glucose-induced NRK-52E cells and the renal tissue of diabetic rats.However,these changes were reversed by luteolin at the administered doses.Additionally,luteolin significantly reduced oxidative stress,inflammation,and fibrosis,as well as improved biochemical parameters in diabetic rats.Furthermore,luteolin at the examined doses markedly alleviated diabetes-induced histopathological changes in renal tissues.Conclusions:Luteolin effectively attenuates streptozotocin-induced diabetic nephropathy in rats by inhibiting MMP-2,MMP-9,and HDAC-2 expression,and reducing oxidative stress and inflammation.展开更多
Gene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesop...Gene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesoporous silica nanoparticles(MSN) are associated with lack of most viral vector drawbacks, such as toxicity, immunogenicity, but also generally a low nucleic acid carrying capacity. To overcome this hurdle, we here modified the pore walls of MSNs with surface-hyperbranching polymerized poly(ethyleneimine)(hbPEI), which provides an abundance of amino-groups for loading of a larger amount of siRNA molecules via electrostatic adsorption. After loading, the particles were covered with a second layer of pre-polymerized PEI to provide better protection of siRNA inside the pores, more effective cellular uptake and endosomal escape. To test the transfection efficiency of PEI covered si RNA/MSNs, MDA-MB 231 breast cancer cells stably expressing GFP were used. We demonstrate that PEI-coated si RNA/MSN complexes provide more effective delivery of si RNAs compared to unmodified MSNs. Thus, it can be concluded that appropriately surface-modified MSNs can be considered as prospective vectors for therapeutic siRNA delivery.展开更多
Results from the in vitro evaluation of the antiparasitaire activity of the aqueous extract, the 80% methanol extract and its fractions from the leaves of Brucea sumatrana against Trypanosoma brucei brucei, T. cruzi, ...Results from the in vitro evaluation of the antiparasitaire activity of the aqueous extract, the 80% methanol extract and its fractions from the leaves of Brucea sumatrana against Trypanosoma brucei brucei, T. cruzi, Leishmania infantum, the multidrug-resistant K1 and chloroquine-sensitive NF54 strains of Plasmodium falciparum indicated that all samples from the leaves extract presented interesting antiparasitaire activity at different extents. The 80% methanol extract, its chloroform acid, petroleum ether and 80% methanol soluble fractions and the aqueous extract exhibited strong activity against Trypanosoma b. brucei, T. cruzi, L. infantum and the multidrug-resistant K1 strain of P. falciparum with IC<sub>50</sub> values from <0.25 to 4.35 μg/ml as well as against chloroquine-sensitive NF54 strain of P. falciparum with IC<sub>50</sub> values ranging from <0.02 to 2.0.4 μg/ml. Most samples were cytotoxic against MRC-5 cell lines (0.2 <sub>50</sub>) < 34.24 μg/ml) and showed good selective effect against all tested parasites. In acute toxicity, the aqueous extract was found to be non-toxic and its LD<sub>50 </sub>was estimated to be greater than 5 g/kg. In addition, it did not significantly modify the concentration levels of some evaluated biochemical and hematological parameters in treated rats. These results constitute a scientific validation supporting and justifying the traditional use of the leaves of B. sumatrana for the treatment of malaria, sleeping sickness and at some extent Chagas disease.展开更多
Co-based catalysts are promising alternatives to precious metals for the selective and effective oxidation of 5-hydroxymethylfurfural(HMF)to the higher value-added 2,5-furandicarboxylic acid(FDCA).However,these cataly...Co-based catalysts are promising alternatives to precious metals for the selective and effective oxidation of 5-hydroxymethylfurfural(HMF)to the higher value-added 2,5-furandicarboxylic acid(FDCA).However,these catalysts still suffer from unsatisfactory activity and poor selectivity.A series of N-doped carbon-supported Co-based dual-metal nanoparticles(NPs)have been designed,among which the Co-Cu_(1.4)-CN_(x) exhibits enhanced HMF oxidative activity,achieving FDCA formation rates 4 times higher than that of pristine Co-CN_(x),with 100%FDCA selectivity.Density functional theory(DFT)calculations evidenced that the increased electron density on Co sites induced by Cu can mediate the positive electronegativity offset to downshift the dband center of Co-Cu_(1.4)-CN_(x),thus reducing the energy barriers for the conversion of HMF to FDCA.Such findings will support the development of superior non-precious metal catalysts for HMF oxidation.展开更多
In clinical practice,we noticed that triple negative breast cancer(TNBC)patients had higher shear-wave elasticity(SWE)stiffness than non-TNBC patients and a higherα-SMA expression was found in TNBC tissues than the n...In clinical practice,we noticed that triple negative breast cancer(TNBC)patients had higher shear-wave elasticity(SWE)stiffness than non-TNBC patients and a higherα-SMA expression was found in TNBC tissues than the non-TNBC tissues.Moreover,SWE stiffness also shows a clear correlation to neoadjuvant response efficiency.To elaborate this phenomenon,TNBC cell membrane-modified polylactide acid-glycolic acid(PLGA)nanoparticle was fabricated to specifically deliver artesunate to regulate SWE stiffness through inhibiting CAFs functional status.As tested in MDA-MB-231 and E0771 orthotopic tumor models,CAFs functional status inhibited by 231M-ARS@PLGA nanoparticles(231M-AP NPs)had reduced the SWE stiffness as well as attenuated hypoxia of tumor as tumor soil loosening agent which amplified the antitumor effects of paclitaxel and PD1 inhibitor.Single-cell sequencing indicated that the two main CAFs(extracellular matrix and wound healing CAFs)that produces extracellular matrix could influence the tumor SWE stiffness as well as the antitumor effect of drugs.Further,biomimetic nanoparticles inhibited CAFs function could attenuate tumor hypoxia by increasing proportion of inflammatory blood vessels and oxygen transport capacity.Therefore,our finding is fundamental for understanding the role of CAFs on affecting SWE stiffness and drugs antitumor effects,which can be further implied in the potential clinical theranostic predicting in neoadjuvant therapy efficacy through non-invasive analyzing of SWE imaging.展开更多
Ischemic stroke is one of the most common public diseases that increase mortality.In the ischemic brain,blood flow restoration can cause the generation of excess reactive oxygen species(ROS).Endogenous anti-oxidases i...Ischemic stroke is one of the most common public diseases that increase mortality.In the ischemic brain,blood flow restoration can cause the generation of excess reactive oxygen species(ROS).Endogenous anti-oxidases in the living system,including catalase(CAT)and superoxide dismutase(SOD),can consume the excess ROS by catalysis to regulate inflammation.However,these natural enzymes are difficult to be widely used in the treatment of stroke.Taking advantages of high stability,low cost,and long-term storage,antioxidative nanozymes-mediated treatments have been proven as a promising method against ischemic stroke.To highlight the progress,we summarize the advances in nanozymes with the antioxidative ability for treating ischemic stroke.It is believed that such a promising therapeutic strategy of antioxidative nanozymes will significantly contribute to the field of ischemic stroke.We expect that antioxidative nanozymes will play significant roles in both basic research and clinical applications.展开更多
Although porphyrin-based metal-organic frameworks(MOFs)have been widely explored as photosensitizers for photodynamic therapy,how the size will affect the light-induced catalytic activity for generation of reactive ox...Although porphyrin-based metal-organic frameworks(MOFs)have been widely explored as photosensitizers for photodynamic therapy,how the size will affect the light-induced catalytic activity for generation of reactive oxygen species(ROS)still remain unclear.Herein,we first report the size-controlled synthesis of two-dimensional(2D)porphyrin-based PCN-134 MOF nanosheets by a two-step solvothermal method to explore the size effect on its PDT performance,thus yielding enhanced photodynamic antimicrobial therapy.By simply controlling the reaction temperature in the synthesis process,the bulk PCN-134 crystal,large PCN-134(L-PCN-134)nanosheets with a lateral size of 2–3μm and thickness of 33.2–37.5 nm and small PCN-134 nanosheets(S-PCN-134)with a lateral size of 160–180 nm and thickness of 9.1–9.7 nm were successfully prepared.Interestingly,the S-PCN-134 nanosheets exhibit much higher photodynamic activity for ROS generation than that of the bulk 3D PCN-134 crystal and L-PCN-134 nanosheets under a660 nm laser irradiation,suggesting that the photodynamic activity of PCN-134 MOF increases when the size reduces.Therefore,the S-PCN-134 nanosheets show much enhanced performance when used as a photosensitizer for photodynamic antimicrobial activity and wound healing.展开更多
Nanozymes are considered to represent a new era of antibacterial agents,while their antibacterial efficiency is limited by the increasing tissue depth of infection.To address this issue,here,we report a copper and sil...Nanozymes are considered to represent a new era of antibacterial agents,while their antibacterial efficiency is limited by the increasing tissue depth of infection.To address this issue,here,we report a copper and silk fibroin(Cu-SF)complex strategy to synthesize alternative copper single-atom nanozymes(SAzymes)with atomically dispersed copper sites anchored on ultrathin 2D porous N-doped carbon nanosheets(CuN_(x)-CNS)and tunable N coordination numbers in the CuN_(x) sites(x=2 or 4).The CuN_(x)-CNS SAzymes inherently possess triple peroxidase(POD)-,catalase(CAT)-,and oxidase(OXD)-like activities,facilitating the conversion of H_(2)O_(2)and O_(2)into reactive oxygen species(ROS)through parallel POD-and OXD-like or cascaded CAT-and OXD-like reactions.Compared to CuN_(2)-CNS,tailoring the N coordination number from 2 to 4 endows the SAzyme(CuN_(4)-CNS)with higher multienzyme activities due to its superior electron structure and lower energy barrier.Meanwhile,CuN_(x)-CNS display strong absorption in the second near-infrared(NIR-II)biowindow with deeper tissue penetration,offering NIR-II-responsive enhanced ROS generation and photothermal treatment in deep tissues.The in vitro and in vivo results demonstrate that the optimal CuN_(4)-CNS can effectively inhibit multidrug-resistant bacteria and eliminate stubborn biofilms,thus exhibiting high therapeutic efficacy in both superficial skin wound and deep implant-related biofilm infections.展开更多
Platinum-based chemotherapy remains the main systemic treatment of ovarian cancer(OC).However,the inevitable development of platinum and poly(adenosine diphosphate-ribose)polymerase inhibitor(PARPi)resistance is assoc...Platinum-based chemotherapy remains the main systemic treatment of ovarian cancer(OC).However,the inevitable development of platinum and poly(adenosine diphosphate-ribose)polymerase inhibitor(PARPi)resistance is associated with poor outcomes,which becomes a major obstacle in the management of this disease.The present study developed“all-in-one”nanoparticles that contained the PARPi olaparib and gallium(Ga)(III)(olaparib-Ga)to effectively reverse PARPi resistance in platinum-resistant A2780-cis and SKOV3-cis OC cells and in SKOV3-cis tumor models.Notably,the olaparib-Ga suppressed SKOV3-cis tumor growth with negligible toxicity.Moreover,the suppression effect was more evident when combining olaparib-Ga with cisplatin or carboplatin,as evaluated in A2780-cis and SKOV3-cis cells.Mechanistically,the combined treatment induced DNA damage,which elicited the activation of ataxia telangiectasia mutated(ATM)/AMT-and Rad3-related(ATR)checkpoint kinase 1(Chk1)/Chk2 signal transduction pathways.This led to the arrest of cell cycle progression at S and G2/M phases,which eventually resulted in apoptosis and cell death due to unrepairable DNA damage.In addition,effective therapeutic responses to olaparib-Ga and cisplatin combination or olaparib-Ga and carboplatin combination were observed in SKOV3-cis tumor-bearing animal models.Altogether,the present findings demonstrate that olaparib-Ga has therapeutic implications in platinum-resistant OC cells,and the combination of olaparib-Ga with cisplatin or carboplatin may be promising for treating patients with OC who exhibit resistance to both PARPi and platinum.展开更多
Skin damage resulting from burns,injuries,or diseases can lead to significant functional and esthetic deficits.However,traditional treatments,such as skin grafting,have limitations including limited donor skin availab...Skin damage resulting from burns,injuries,or diseases can lead to significant functional and esthetic deficits.However,traditional treatments,such as skin grafting,have limitations including limited donor skin availability,poor aesthetics,and functional impairment.Skin tissue engineering provides a promising alternative,with engineered artificial skins offering a highly viable avenue.Engineered artificial skin is designed to mimic or replace the functions of natural human skin and find applications in various medical treatments,particularly for severe burns,chronic wounds,and other skin injuries or defects.These artificial skins aim to promote wound healing,provide temporary coverage,permanent skin replacement,and restore the skin’s barrier function.Artificial skins have diverse applications in medicine and wound care,addressing burns,chronic wounds,and traumatic injuries.They also serve as valuable tools for research in tissue engineering,offering experimental models for studying wound healing mechanisms,testing new biomaterials,and exploring innovative approaches to skin regeneration.This review provides an overview of current construction strategies for engineered artificial skin,including cell sources,biomaterials,and construction techniques.It further explores the primary application areas and future prospects of artificial skin,highlighting their potential to revolutionize skin reconstruction and advance the field of regenerative medicine.展开更多
Lung cancer has become one of the key life-threatening factors and is the most common type of tumor.With the improvement of equipment and the improvement of lung cancer awareness,the surgical treatment of lung cancer ...Lung cancer has become one of the key life-threatening factors and is the most common type of tumor.With the improvement of equipment and the improvement of lung cancer awareness,the surgical treatment of lung cancer is becoming more and more mature.Surgery can provide an important part of individualized treatment strategies for patients with different stages of lung cancer and different wishes.In addition,the concept of minimally invasive,precise,and intelligent has triggered a revolutionary change in the surgical treatment strategy for lung cancer.Therefore,this review focuses on the development of lung cancer surgery history,summarizing the era from traditional surgery to the era of minimally invasive thoracic surgery based on TV-assisted thoracic surgery.The operating methods and treatment effects of different surgical methods are comprehensively introduced,and the optimization and improvement of different surgical methods in the future are also discussed.Along with the concept of minimally invasive surgical techniques,there are more and more explorations of nanotechnology in the surgical treatment of lung cancer.The application of nanotechnology in lung cancer imaging,and the combination of surgery with nanomedicine is an effective solution for cancer treatment today.So,this review also summarizes the application prospects of nanotechnology before,during and after lung cancer surgery.展开更多
Oligonucleotide-based therapy has experienced remarkable development in the past 2 decades,but its broad applications are severely hampered by delivery vectors.Widely used viral vectors and lipid nanovectors are suffe...Oligonucleotide-based therapy has experienced remarkable development in the past 2 decades,but its broad applications are severely hampered by delivery vectors.Widely used viral vectors and lipid nanovectors are suffering from immune clearance after repeating usage or requiring refrigerated transportation and storage,respectively.In this work,amino-modified virus-mimetic spike silica nanoparticles(NH_(2)-SSNs)were fabricated using a 1-pot surfactant-free approach with controlled spike lengths,which were demonstrated with excellent delivery performance and biosafety in nearly all cell types and mice.It indicated that NH2-SSNs entered cells by spike-dependent cell membrane docking and dynamin-dependent endocytosis.The positively charged spikes with proper length on the surface can facilitate the efficient encapsulation of RNAs,protect the loaded RNAs from degradation,and trigger an early endosome escape during intracellular trafficking,similarly to the cellular internalization mechanism of virions.Regarding the fantastic properties of NH_(2)-SSNs in nucleic acid delivery,it revealed that nanoparticles with solid spikes on the surface would be excellent vehicles for gene therapy,presenting self-evident advantages in storage,transportation,modification,and quality control in large-scale production compared to lipid nanovectors.展开更多
Artificial sweeteners(AS)have been widely applied in the food industry as sugar substitutes with reduced calorie content but high sweetening power[1].The consumption of sugar-sweetened beverages is associated with the...Artificial sweeteners(AS)have been widely applied in the food industry as sugar substitutes with reduced calorie content but high sweetening power[1].The consumption of sugar-sweetened beverages is associated with the incidence of obesity and type 2 diabetes[2,3].Non-caloric AS(NCAS)have been recommended for weight management and as a treatment strategy for type 2 diabetes[4].While AS are generally considered safe with acceptable daily intake by regulatory agencies(e.g.,European Food Safety Authority,US Food and Drug Administration),mounting epidemiological evidence shows that the consumption of AS is associated with the risk of cardiometabolic disease[2,3,5].展开更多
In the new issue of Cell,Dr.Meisel’s teamcharacterized how the orally administrated probiotic bacteria Lactobacillus reuteri(Lr)translocated from the gut to tumors in mice with melanoma.1 Furthermore,its production o...In the new issue of Cell,Dr.Meisel’s teamcharacterized how the orally administrated probiotic bacteria Lactobacillus reuteri(Lr)translocated from the gut to tumors in mice with melanoma.1 Furthermore,its production of a compound called indole-3-aldehyde(I3A)derived fromdietary tryptophan directly stimulates immune cells to make cancer immunotherapy more effective(Figure 1A).展开更多
Fungi are widely distributed in the environment,and some are beneficial to medicine,industry,agriculture,and food.For example,Penicillium chrysogenum,Acremonium chrysogenum,and Aspergillus terreus can synthesizeβ-lac...Fungi are widely distributed in the environment,and some are beneficial to medicine,industry,agriculture,and food.For example,Penicillium chrysogenum,Acremonium chrysogenum,and Aspergillus terreus can synthesizeβ-lactams,which can be used as drugs[1];Aspergillus niger and Trichoderma reesei are well-known industrial enzyme producers[2].展开更多
Bladder cancer is one of the concerning malignancies worldwide,which is lacking effective targeted therapy.Gene therapy is a potential approach for bladder cancer treatment.While,a safe and effective targeted gene del...Bladder cancer is one of the concerning malignancies worldwide,which is lacking effective targeted therapy.Gene therapy is a potential approach for bladder cancer treatment.While,a safe and effective targeted gene delivery system is urgently needed for prompting the bladder cancer treatment in vivo.In this study,we confirmed that the bladder cancer had CD44 overexpression and small interfering RNAs(siRNA)with high interfere to Bcl2 oncogene were designed and screened.Then hyaluronic acid dialdehyde(HAD)was prepared in an ethanol-water mixture and covalently conjugated to the chitosan nanoparticles(CS-HAD NPs)to achieve CD44 targeted siRNA delivery.The in vitro and in vivo evaluations indicated that the siRNA-loaded CS-HAD NPs(siRNA@CS-HAD NPs)were approximately 100 nm in size,with improved stability,high siRNA encapsulation efficiency and low cytotoxicity.CS-HAD NPs could target to CD44 receptor and deliver the therapeutic siRNA into T24 bladder cancer cells through a ligand-receptor-mediated targeting mechanism and had a specific accumulation capacity in vivo to interfere the targeted oncogene Bcl2 in bladder cancer.Overall,a CD44 targeted gene delivery system based on natural macromolecules was developed for effective bladder cancer treatment,which could be more conducive to clinical application due to its simple preparation and high biological safety.展开更多
Immune cells play a crucial regulatory role in inflammatory phase and proliferative phase during skin healing.How to programmatically activate sequential immune responses is the key for scarless skin regeneration.In t...Immune cells play a crucial regulatory role in inflammatory phase and proliferative phase during skin healing.How to programmatically activate sequential immune responses is the key for scarless skin regeneration.In this study,an“Inner-Outer”IL-10-loaded electrospun fiber with cascade release behavior was constructed.During the inflammatory phase,the electrospun fiber released a lower concentration of IL-10 within the wound,inhibiting excessive recruitment of inflammatory cells and polarizing macrophages into anti-inflammatory phenotype“M2c”to suppress excessive inflammation response.During the proliferative phase,a higher concentration of IL-10 released by the fiber and the anti-fibrotic cytokines secreted by polarized“M2c”directly acted on dermal fibroblasts to simultaneously inhibit extracellular matrix overdeposition and promote fibroblast migration.The“Inner-Outer”IL-10-loaded electrospun fiber programmatically activated the sequential immune responses during wound healing and led to scarless skin regeneration,which is a promising immunomodulatory biomaterial with great potential for promoting complete tissue regeneration.展开更多
Therapeutic oligonucleotides(TOs)represent one of the most promising drug candidates in the targeted cancer treatment due to their high specificity and capability of modulating cellular pathways that are not readily d...Therapeutic oligonucleotides(TOs)represent one of the most promising drug candidates in the targeted cancer treatment due to their high specificity and capability of modulating cellular pathways that are not readily druggable.However,efficiently delivering of TOs to cancer cellular targets is still the biggest challenge in promoting their clinical translations.Emerging as a significant drug delivery vector,nanoparticles(NPs)can not only protect TOs from nuclease degradation and enhance their tumor accumulation,but also can improve the cell uptake efficiency of TOs as well as the following endosomal escape to increase the therapeutic index.Furthermore,targeted and on-demand drug release of TOs can also be approached to minimize the risk of toxicity towards normal tissues using stimuli-responsive NPs.In the past decades,remarkable progresses have been made on the TOs delivery based on various NPs with specific purposes.In this review,we will first give a brief introduction on the basis of TOs as well as the action mechanisms of several typical TOs,and then describe the obstacles that prevent the clinical translation of TOs,followed by a comprehensive overview of the recent progresses on TOs delivery based on several various types of nanocarriers containing lipid-based nanoparticles,polymeric nanoparticles,gold nanoparticles,porous nanoparticles,DNA/RNA nanoassembly,extracellular vesicles,and imaging-guided drug delivery nanoparticles.展开更多
Biofunctionalization of artificial nerve implants by incorporation of specific bioactive factors has greatly enhanced the success of grafting procedures for peripheral nerve regeneration.However,most studies on novel ...Biofunctionalization of artificial nerve implants by incorporation of specific bioactive factors has greatly enhanced the success of grafting procedures for peripheral nerve regeneration.However,most studies on novel biofunctionalized implants have emphasized the promotion of neuronal and axonal repair over vascularization,a process critical for long-term functional restoration.We constructed a dual-biofunctionalized chitosan/collagen composite scaffold with Ile-Lys-Val-Ala-Val(IKVAV)and vascular endothelial growth factor(VEGF)by combining solution blending,in situ lyophilization,and surface biomodification.Immobilization of VEGF and IKVAV on the scaffolds was confirmed both qualitatively by staining and quantitatively by ELISA.Various single-and dual-biofunctionalized scaffolds were compared for the promotion of endothelial cell(EC)and Schwann cell(SC)proliferation as well as the induction of angiogenic and neuroregeneration-associated genes by these cells in culture.The efficacy of these scaffolds for vascularization was evaluated by implantation in chicken embryos,while functional repair capacity in vivo was assessed in rats subjected to a 10mm sciatic nerve injury.Dual-biofunctionalized scaffolds supported robust EC and SC proliferation and upregulated the expression levels of multiple genes and proteins related to neuroregeneration and vascularization.Dual-biofunctionalized scaffolds demonstrated superior vascularization induction in embryos and greater promotion of vascularization,myelination,and functional recovery in rats.These findings support the clinical potential of VEGF/IKVAV dual-biofunctionalized chitosan/collagen composite scaffolds for facilitating peripheral nerve regeneration,making it an attractive candidate for repairing critical nerve defect.The study may provide a critical experimental and theoretical basis for the development and design of new artificial nerve implants with excellent biological performance.展开更多
基金supported by the Ruijin Hospital Guangci Introducing Talent Projectfinancial support from National Natural Science Foundation of China(82372145)+4 种基金the Research Fellow(Grant No.353146)Research Project(347897)Solutions for Health Profile(336355)InFLAMES Flagship(337531)grants from Academy of Finlandthe Finland China Food and Health International Pilot Project funded by the Finnish Ministry of Education and Culture.
文摘Chronic diabetic wounds confront a significant medical challenge because of increasing prevalence and difficult-healing circumstances.It is vital to develop multifunctional hydrogel dressings,with well-designed morphology and structure to enhance flexibility and effectiveness in wound management.To achieve these,we propose a self-healing hydrogel dressing based on structural color microspheres for wound management.The microsphere comprised a photothermal-responsive inverse opal framework,which was constructed by hyaluronic acid methacryloyl,silk fibroin methacryloyl and black phosphorus quantum dots(BPQDs),and was further re-filled with a dynamic hydrogel.The dynamic hydrogel filler was formed by Knoevenagel condensation reaction between cyanoacetate and benzaldehyde-functionalized dextran(DEX-CA and DEX-BA).Notably,the composite microspheres can be applied arbitrarily,and they can adhere together upon near-infrared irradiation by leveraging the BPQDs-mediated photothermal effect and the thermoreversible stiffness change of dynamic hydrogel.Additionally,eumenitin and vascular endothelial growth factor were co-loaded in the microspheres and their release behavior can be regulated by the same mechanism.Moreover,effective monitoring of the drug release process can be achieved through visual color variations.The microsphere system has demonstrated desired capabilities of controllable drug release and efficient wound management.These characteristics suggest broad prospects for the proposed composite microspheres in clinical applications.
基金supported by the Joe,Pentti,and Tor Borg Memorial Fund.
文摘Objective:To investigate the renoprotective effects of luteolin on diabetes in rats.Methods:One week after administration of streptozotocin 55 mg/kg intraperitoneally,rats were given 25,50,and 75 mg/kg/day of luteolin orally for another eight weeks.At the end of the experiment,body weight,blood glucose level,biochemical parameters for renal function(serum creatinine,blood urea nitrogen,uric acid,serum albumin,and total protein),kidney histology,matrix metalloproteinase(MMP)-2,MMP-9,and histone deacetylase 2(HDAC-2)expression,and malondialdehyde,myeloperoxidase,and hydroxyproline content in renal tissue were evaluated.High glucose-induced damage using NRK-52E cell line was studied to evaluate cell viability and metalloenzyme expression.Additionally,in silico studies including docking and molecular dynamics simulations were conducted.Results:MMP-2,MMP-9,and HDAC-2 expressions were significantly increased in high glucose-induced NRK-52E cells and the renal tissue of diabetic rats.However,these changes were reversed by luteolin at the administered doses.Additionally,luteolin significantly reduced oxidative stress,inflammation,and fibrosis,as well as improved biochemical parameters in diabetic rats.Furthermore,luteolin at the examined doses markedly alleviated diabetes-induced histopathological changes in renal tissues.Conclusions:Luteolin effectively attenuates streptozotocin-induced diabetic nephropathy in rats by inhibiting MMP-2,MMP-9,and HDAC-2 expression,and reducing oxidative stress and inflammation.
基金supported in part by Russian Science Founda-tion grant 17-15-01230(biological characterization)Academy of Finland project nos.284542,384542(JMR)+2 种基金Jane and Aatos Erkko Foundation(EC)Anna Egorova is supported by President of Russian Federation scholarship(SP-2162.2015.4)Anna Slita was supported by the scholarship within Saint Pe-tersburg State University bilateral exchange program for study abroad
文摘Gene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesoporous silica nanoparticles(MSN) are associated with lack of most viral vector drawbacks, such as toxicity, immunogenicity, but also generally a low nucleic acid carrying capacity. To overcome this hurdle, we here modified the pore walls of MSNs with surface-hyperbranching polymerized poly(ethyleneimine)(hbPEI), which provides an abundance of amino-groups for loading of a larger amount of siRNA molecules via electrostatic adsorption. After loading, the particles were covered with a second layer of pre-polymerized PEI to provide better protection of siRNA inside the pores, more effective cellular uptake and endosomal escape. To test the transfection efficiency of PEI covered si RNA/MSNs, MDA-MB 231 breast cancer cells stably expressing GFP were used. We demonstrate that PEI-coated si RNA/MSN complexes provide more effective delivery of si RNAs compared to unmodified MSNs. Thus, it can be concluded that appropriately surface-modified MSNs can be considered as prospective vectors for therapeutic siRNA delivery.
文摘Results from the in vitro evaluation of the antiparasitaire activity of the aqueous extract, the 80% methanol extract and its fractions from the leaves of Brucea sumatrana against Trypanosoma brucei brucei, T. cruzi, Leishmania infantum, the multidrug-resistant K1 and chloroquine-sensitive NF54 strains of Plasmodium falciparum indicated that all samples from the leaves extract presented interesting antiparasitaire activity at different extents. The 80% methanol extract, its chloroform acid, petroleum ether and 80% methanol soluble fractions and the aqueous extract exhibited strong activity against Trypanosoma b. brucei, T. cruzi, L. infantum and the multidrug-resistant K1 strain of P. falciparum with IC<sub>50</sub> values from <0.25 to 4.35 μg/ml as well as against chloroquine-sensitive NF54 strain of P. falciparum with IC<sub>50</sub> values ranging from <0.02 to 2.0.4 μg/ml. Most samples were cytotoxic against MRC-5 cell lines (0.2 <sub>50</sub>) < 34.24 μg/ml) and showed good selective effect against all tested parasites. In acute toxicity, the aqueous extract was found to be non-toxic and its LD<sub>50 </sub>was estimated to be greater than 5 g/kg. In addition, it did not significantly modify the concentration levels of some evaluated biochemical and hematological parameters in treated rats. These results constitute a scientific validation supporting and justifying the traditional use of the leaves of B. sumatrana for the treatment of malaria, sleeping sickness and at some extent Chagas disease.
基金the National Natural Science Foundation of China(Nos.51902281,51801075,and 82160421)the Natural Science Foundation of Jiangsu Province(No.BK20211322)the Scientific and Technological Projects of Henan Province(No.212102210293).
文摘Co-based catalysts are promising alternatives to precious metals for the selective and effective oxidation of 5-hydroxymethylfurfural(HMF)to the higher value-added 2,5-furandicarboxylic acid(FDCA).However,these catalysts still suffer from unsatisfactory activity and poor selectivity.A series of N-doped carbon-supported Co-based dual-metal nanoparticles(NPs)have been designed,among which the Co-Cu_(1.4)-CN_(x) exhibits enhanced HMF oxidative activity,achieving FDCA formation rates 4 times higher than that of pristine Co-CN_(x),with 100%FDCA selectivity.Density functional theory(DFT)calculations evidenced that the increased electron density on Co sites induced by Cu can mediate the positive electronegativity offset to downshift the dband center of Co-Cu_(1.4)-CN_(x),thus reducing the energy barriers for the conversion of HMF to FDCA.Such findings will support the development of superior non-precious metal catalysts for HMF oxidation.
基金National Natural Science Foundation of China(NO.81830058,82071945,81401422,81871472)Shanghai Committee of Science and Technology,China(No.21S31905400)+2 种基金Research Fellow(Grant No.328933),project(347897)Solutions for Health Profile(336355)InFLAMES Flagship(337531)projects from Academy of Finland,Finland China Food and Health International Pilot Project funded by the Finnish Ministry of Education and Culture.
文摘In clinical practice,we noticed that triple negative breast cancer(TNBC)patients had higher shear-wave elasticity(SWE)stiffness than non-TNBC patients and a higherα-SMA expression was found in TNBC tissues than the non-TNBC tissues.Moreover,SWE stiffness also shows a clear correlation to neoadjuvant response efficiency.To elaborate this phenomenon,TNBC cell membrane-modified polylactide acid-glycolic acid(PLGA)nanoparticle was fabricated to specifically deliver artesunate to regulate SWE stiffness through inhibiting CAFs functional status.As tested in MDA-MB-231 and E0771 orthotopic tumor models,CAFs functional status inhibited by 231M-ARS@PLGA nanoparticles(231M-AP NPs)had reduced the SWE stiffness as well as attenuated hypoxia of tumor as tumor soil loosening agent which amplified the antitumor effects of paclitaxel and PD1 inhibitor.Single-cell sequencing indicated that the two main CAFs(extracellular matrix and wound healing CAFs)that produces extracellular matrix could influence the tumor SWE stiffness as well as the antitumor effect of drugs.Further,biomimetic nanoparticles inhibited CAFs function could attenuate tumor hypoxia by increasing proportion of inflammatory blood vessels and oxygen transport capacity.Therefore,our finding is fundamental for understanding the role of CAFs on affecting SWE stiffness and drugs antitumor effects,which can be further implied in the potential clinical theranostic predicting in neoadjuvant therapy efficacy through non-invasive analyzing of SWE imaging.
基金supported by the National Natural Science Foundation of China (82102335 and 82101184)the Postdoctoral Science Foundation of China (2021TQ0218 and 2022M722207)+5 种基金Shenzhen Fundamental Research Program (JCYJ20210324102809024)Shenzhen PhD Start-up Program (RCBS20210609103713045)the International Coop-erative Project of Shenzhen Science and Technology Innovation Committee (GJHZ20200731095602009)the Shenzhen Key Laboratory of Translational Medicine of Biomaterials,the Science and Technology Innovation Commission of Shenzhen (ZDSYS20200811142600003)the Shenzhen Medical Cure and Prevention Integration Program of Nervous System Diseasethe Quality Control and Improvement Program of Treatment of Acute Ischemic Stroke.
文摘Ischemic stroke is one of the most common public diseases that increase mortality.In the ischemic brain,blood flow restoration can cause the generation of excess reactive oxygen species(ROS).Endogenous anti-oxidases in the living system,including catalase(CAT)and superoxide dismutase(SOD),can consume the excess ROS by catalysis to regulate inflammation.However,these natural enzymes are difficult to be widely used in the treatment of stroke.Taking advantages of high stability,low cost,and long-term storage,antioxidative nanozymes-mediated treatments have been proven as a promising method against ischemic stroke.To highlight the progress,we summarize the advances in nanozymes with the antioxidative ability for treating ischemic stroke.It is believed that such a promising therapeutic strategy of antioxidative nanozymes will significantly contribute to the field of ischemic stroke.We expect that antioxidative nanozymes will play significant roles in both basic research and clinical applications.
基金the funding support from the National Natural Science Foundation of China(No.52102348)the funding support from the National Natural Science Foundation of China(No.52173143)+6 种基金the funding support from the National Natural Science Foundation of China(No.22005259)the Science and Technology Innovation Talent Program of University in Henan Province(No.23HASTIT016)the funding support from China Postdoctoral Science Foundation(No.2021M701113)the Start-Up Grant(No.9610495)from City University of Hong Kongthe funding support from the National Natural Science Foundation of China(No.21905195)Natural Science Foundation of Tianjin City(No.20JCYBJC00800)the PEIYANG Young Scholars Program of Tianjin University(No.2020XRX-0023)。
文摘Although porphyrin-based metal-organic frameworks(MOFs)have been widely explored as photosensitizers for photodynamic therapy,how the size will affect the light-induced catalytic activity for generation of reactive oxygen species(ROS)still remain unclear.Herein,we first report the size-controlled synthesis of two-dimensional(2D)porphyrin-based PCN-134 MOF nanosheets by a two-step solvothermal method to explore the size effect on its PDT performance,thus yielding enhanced photodynamic antimicrobial therapy.By simply controlling the reaction temperature in the synthesis process,the bulk PCN-134 crystal,large PCN-134(L-PCN-134)nanosheets with a lateral size of 2–3μm and thickness of 33.2–37.5 nm and small PCN-134 nanosheets(S-PCN-134)with a lateral size of 160–180 nm and thickness of 9.1–9.7 nm were successfully prepared.Interestingly,the S-PCN-134 nanosheets exhibit much higher photodynamic activity for ROS generation than that of the bulk 3D PCN-134 crystal and L-PCN-134 nanosheets under a660 nm laser irradiation,suggesting that the photodynamic activity of PCN-134 MOF increases when the size reduces.Therefore,the S-PCN-134 nanosheets show much enhanced performance when used as a photosensitizer for photodynamic antimicrobial activity and wound healing.
基金the National Natural Science Foundation of China(32222041,82072425,82160421,and 82072498)the Natural Science Foundation of Jiangsu Province(BE2020666,BK20211322,and BK20220059)+3 种基金Finland-China Food and Health International Pilot Project funded by the Finnish Ministry of Education and Culture,the Academy Research Fellow(328933)Solutions for Health Strategic Research Profiling Area(336355)InFLAMES Flagship(337531)Grants from Academy of Finland,the Special Project of Diagnosis and Treatment for Clinical Diseases of Suzhou(LCZX202003)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),and the jiangsu Specially Appointed Professor"Program and Postgraduate Research&Practice Innovation Program of jiangsu Province(KYCX22_3217).
文摘Nanozymes are considered to represent a new era of antibacterial agents,while their antibacterial efficiency is limited by the increasing tissue depth of infection.To address this issue,here,we report a copper and silk fibroin(Cu-SF)complex strategy to synthesize alternative copper single-atom nanozymes(SAzymes)with atomically dispersed copper sites anchored on ultrathin 2D porous N-doped carbon nanosheets(CuN_(x)-CNS)and tunable N coordination numbers in the CuN_(x) sites(x=2 or 4).The CuN_(x)-CNS SAzymes inherently possess triple peroxidase(POD)-,catalase(CAT)-,and oxidase(OXD)-like activities,facilitating the conversion of H_(2)O_(2)and O_(2)into reactive oxygen species(ROS)through parallel POD-and OXD-like or cascaded CAT-and OXD-like reactions.Compared to CuN_(2)-CNS,tailoring the N coordination number from 2 to 4 endows the SAzyme(CuN_(4)-CNS)with higher multienzyme activities due to its superior electron structure and lower energy barrier.Meanwhile,CuN_(x)-CNS display strong absorption in the second near-infrared(NIR-II)biowindow with deeper tissue penetration,offering NIR-II-responsive enhanced ROS generation and photothermal treatment in deep tissues.The in vitro and in vivo results demonstrate that the optimal CuN_(4)-CNS can effectively inhibit multidrug-resistant bacteria and eliminate stubborn biofilms,thus exhibiting high therapeutic efficacy in both superficial skin wound and deep implant-related biofilm infections.
基金the National Natural Science Foundation of China(82072855)the Fundamental Research Funds for the Central Universities(2021FZZX001-43)+6 种基金Innovative Talent Plan of Zhejiang Health Science and Technology Project(2021RC086)the Beijing Kanghua Foundation for the Development of Traditional Chinese and Western Medicine(KH-2021-LLZX-016)4+X Clinical Research Project of Women's Hospital,School of Medicine,Zhejiang University(ZDFY2022-4X202)WHZJU Global Partnership Seed Fund(G2022A003)H.Z.acknowledges financial support from the research fellow(grant no.353146),project(347897)solutions for Health Profile(336355)InFLAMES Flagship(337531)grants from Academy of Finland,and the Finland China Food and Health International Pilot Project funded by the Finnish Ministry of Education and Culture(no.280Mo052K1).
文摘Platinum-based chemotherapy remains the main systemic treatment of ovarian cancer(OC).However,the inevitable development of platinum and poly(adenosine diphosphate-ribose)polymerase inhibitor(PARPi)resistance is associated with poor outcomes,which becomes a major obstacle in the management of this disease.The present study developed“all-in-one”nanoparticles that contained the PARPi olaparib and gallium(Ga)(III)(olaparib-Ga)to effectively reverse PARPi resistance in platinum-resistant A2780-cis and SKOV3-cis OC cells and in SKOV3-cis tumor models.Notably,the olaparib-Ga suppressed SKOV3-cis tumor growth with negligible toxicity.Moreover,the suppression effect was more evident when combining olaparib-Ga with cisplatin or carboplatin,as evaluated in A2780-cis and SKOV3-cis cells.Mechanistically,the combined treatment induced DNA damage,which elicited the activation of ataxia telangiectasia mutated(ATM)/AMT-and Rad3-related(ATR)checkpoint kinase 1(Chk1)/Chk2 signal transduction pathways.This led to the arrest of cell cycle progression at S and G2/M phases,which eventually resulted in apoptosis and cell death due to unrepairable DNA damage.In addition,effective therapeutic responses to olaparib-Ga and cisplatin combination or olaparib-Ga and carboplatin combination were observed in SKOV3-cis tumor-bearing animal models.Altogether,the present findings demonstrate that olaparib-Ga has therapeutic implications in platinum-resistant OC cells,and the combination of olaparib-Ga with cisplatin or carboplatin may be promising for treating patients with OC who exhibit resistance to both PARPi and platinum.
基金supported by grants from National Natural Science Foundation of China(NO.81974288)National Natural Science Foundation of China(NO.82302812)Natural Science Foundation of Zhejiang Province of China(LQ22E030004),。
文摘Skin damage resulting from burns,injuries,or diseases can lead to significant functional and esthetic deficits.However,traditional treatments,such as skin grafting,have limitations including limited donor skin availability,poor aesthetics,and functional impairment.Skin tissue engineering provides a promising alternative,with engineered artificial skins offering a highly viable avenue.Engineered artificial skin is designed to mimic or replace the functions of natural human skin and find applications in various medical treatments,particularly for severe burns,chronic wounds,and other skin injuries or defects.These artificial skins aim to promote wound healing,provide temporary coverage,permanent skin replacement,and restore the skin’s barrier function.Artificial skins have diverse applications in medicine and wound care,addressing burns,chronic wounds,and traumatic injuries.They also serve as valuable tools for research in tissue engineering,offering experimental models for studying wound healing mechanisms,testing new biomaterials,and exploring innovative approaches to skin regeneration.This review provides an overview of current construction strategies for engineered artificial skin,including cell sources,biomaterials,and construction techniques.It further explores the primary application areas and future prospects of artificial skin,highlighting their potential to revolutionize skin reconstruction and advance the field of regenerative medicine.
基金supported by Application Research Center of 3D simulation engineering technology for diagnosis and treatment of chest diseases Project No.:20130604050tcappreciated that the Academy of Finland (InFLAMES Flagship Grant No.337531)+3 种基金research Fellow (Grant No.328933)project (347897)solutions for Health Pro-file (336355)the Finland China Food and Health International Pilot Project funded by the Finnish Ministry of Education and Culture,and China Scholarship Council support this work.
文摘Lung cancer has become one of the key life-threatening factors and is the most common type of tumor.With the improvement of equipment and the improvement of lung cancer awareness,the surgical treatment of lung cancer is becoming more and more mature.Surgery can provide an important part of individualized treatment strategies for patients with different stages of lung cancer and different wishes.In addition,the concept of minimally invasive,precise,and intelligent has triggered a revolutionary change in the surgical treatment strategy for lung cancer.Therefore,this review focuses on the development of lung cancer surgery history,summarizing the era from traditional surgery to the era of minimally invasive thoracic surgery based on TV-assisted thoracic surgery.The operating methods and treatment effects of different surgical methods are comprehensively introduced,and the optimization and improvement of different surgical methods in the future are also discussed.Along with the concept of minimally invasive surgical techniques,there are more and more explorations of nanotechnology in the surgical treatment of lung cancer.The application of nanotechnology in lung cancer imaging,and the combination of surgery with nanomedicine is an effective solution for cancer treatment today.So,this review also summarizes the application prospects of nanotechnology before,during and after lung cancer surgery.
基金the National Natu ral Science Foundation of China(U22A20582,X.W.,22005197,J.F.,61435010 and 61575089,Han Z.,U1803128,M.Q.,81991525,X.W.,81871472,Han Z.)the Natural Science Founda-tion of Shandong Province(ZR202110150015,ZR2021LSW013,ZR202110290057)+8 种基金the China Postdoctoral Science Foun-dation(Grant No.2021M692197,J.F.)State Key Research Development Program of China(2019YFB2203503,Han Z.)the Science and Technology Innovation Commission of Shenzhen(KQTD2015032416270385,JCYJ20150625103619275,Han Z.,JCYJ20180305124854790,M.Q.)the Natural Science Foun-dation of Guangdong Province(2018A030310500)the Taishan Scholar Project(tsqn201909054,tsqn201909170)the Fundamental Research Funds for the Central Universities to X.W.and M.Q.,and Tor,Joe and Pentti Borg Memorial Fund(R.B.).This project was funded by the Deanship of Scientific Research(DSR)at King Abdulaziz University,Jeddah,under grant no.(KEP-MSc-70-130-42).The Research Fellow(Grant No.328933)Solutions for Health Profile(336355)InFLAMES Flagship(337531)projects from Academy of Finland,as well as the Finland-China Food and Health(FCFH)International Pilot Project funded by the Finnish Ministry of Education and Culture are acknowledged.
文摘Oligonucleotide-based therapy has experienced remarkable development in the past 2 decades,but its broad applications are severely hampered by delivery vectors.Widely used viral vectors and lipid nanovectors are suffering from immune clearance after repeating usage or requiring refrigerated transportation and storage,respectively.In this work,amino-modified virus-mimetic spike silica nanoparticles(NH_(2)-SSNs)were fabricated using a 1-pot surfactant-free approach with controlled spike lengths,which were demonstrated with excellent delivery performance and biosafety in nearly all cell types and mice.It indicated that NH2-SSNs entered cells by spike-dependent cell membrane docking and dynamin-dependent endocytosis.The positively charged spikes with proper length on the surface can facilitate the efficient encapsulation of RNAs,protect the loaded RNAs from degradation,and trigger an early endosome escape during intracellular trafficking,similarly to the cellular internalization mechanism of virions.Regarding the fantastic properties of NH_(2)-SSNs in nucleic acid delivery,it revealed that nanoparticles with solid spikes on the surface would be excellent vehicles for gene therapy,presenting self-evident advantages in storage,transportation,modification,and quality control in large-scale production compared to lipid nanovectors.
基金funded the National Natural Science Foundation of China(No.32111530179).
文摘Artificial sweeteners(AS)have been widely applied in the food industry as sugar substitutes with reduced calorie content but high sweetening power[1].The consumption of sugar-sweetened beverages is associated with the incidence of obesity and type 2 diabetes[2,3].Non-caloric AS(NCAS)have been recommended for weight management and as a treatment strategy for type 2 diabetes[4].While AS are generally considered safe with acceptable daily intake by regulatory agencies(e.g.,European Food Safety Authority,US Food and Drug Administration),mounting epidemiological evidence shows that the consumption of AS is associated with the risk of cardiometabolic disease[2,3,5].
基金the financial support for this research received fromthe Health and Medical Research Fund of Hong Kong(10212276)National Natural Science Foundation of China(Nos.32071301,32111530179,32270886,and 32070827)+5 种基金National Key R&D Program of China(2022YFA1106400 and 2020YFA0803201)Key laboratory tasks(LG202103-01-07)Youth Innovation Promotion Association of CAS(2021264)Shanghai Natural Science Foundation(22ZR1469800)Outstanding Youth Reserve Talent Project(IDF201370/074)Scientific Research Foundation for the introduction of talent(JIF201035Y).
文摘In the new issue of Cell,Dr.Meisel’s teamcharacterized how the orally administrated probiotic bacteria Lactobacillus reuteri(Lr)translocated from the gut to tumors in mice with melanoma.1 Furthermore,its production of a compound called indole-3-aldehyde(I3A)derived fromdietary tryptophan directly stimulates immune cells to make cancer immunotherapy more effective(Figure 1A).
基金This study was funded by the National Natural Science Foundation of China(No.32111530179).
文摘Fungi are widely distributed in the environment,and some are beneficial to medicine,industry,agriculture,and food.For example,Penicillium chrysogenum,Acremonium chrysogenum,and Aspergillus terreus can synthesizeβ-lactams,which can be used as drugs[1];Aspergillus niger and Trichoderma reesei are well-known industrial enzyme producers[2].
基金This study was financially supported by the National Natural Science Foundation of China(81772713,81472411,81401899,81372752)Taishan Scholar Program of Shandong Province(tsqn20161077)+4 种基金Key Research and Development Program of Shandong Province(2018GSF118197)China Postdoctoral Science Foundation(2017M622144)Qingdao Postdoctoral Application Research Project.Prof.Zhang acknowledged the support from Academy of Finland(Grant no.328933)Sigrid Juselius Foundation(Grant no.28002247K1)We thank Dr.Chang Liu fromÅbo Akademi University for giving some advice to analyze the TGA data,and Ms.Qian Wen from Biomedical Center of Qingdao University for her guidance and support of in vivo fluorescence imaging.
文摘Bladder cancer is one of the concerning malignancies worldwide,which is lacking effective targeted therapy.Gene therapy is a potential approach for bladder cancer treatment.While,a safe and effective targeted gene delivery system is urgently needed for prompting the bladder cancer treatment in vivo.In this study,we confirmed that the bladder cancer had CD44 overexpression and small interfering RNAs(siRNA)with high interfere to Bcl2 oncogene were designed and screened.Then hyaluronic acid dialdehyde(HAD)was prepared in an ethanol-water mixture and covalently conjugated to the chitosan nanoparticles(CS-HAD NPs)to achieve CD44 targeted siRNA delivery.The in vitro and in vivo evaluations indicated that the siRNA-loaded CS-HAD NPs(siRNA@CS-HAD NPs)were approximately 100 nm in size,with improved stability,high siRNA encapsulation efficiency and low cytotoxicity.CS-HAD NPs could target to CD44 receptor and deliver the therapeutic siRNA into T24 bladder cancer cells through a ligand-receptor-mediated targeting mechanism and had a specific accumulation capacity in vivo to interfere the targeted oncogene Bcl2 in bladder cancer.Overall,a CD44 targeted gene delivery system based on natural macromolecules was developed for effective bladder cancer treatment,which could be more conducive to clinical application due to its simple preparation and high biological safety.
基金This work was supported by the National Key Research and Development Program of China(2020YFA0908200)National Natural Science Foundation of China(81701907 and 81871472)+7 种基金The in vitro biological experiment was supported by National Natural Science Foundation of China(81772099 and 81801928)Shanghai Sailing Program(18YF1412400)The production and detection of the scaffold were supported by Shanghai Jiao Tong University“Medical and Research”Program(ZH2018ZDA04)Science and Technology Commission of Shanghai Municipality(19440760400)The in vivo biological experiment were supported Pujiang program of SSTC(18PJ1407100)Prof.H.Zhang acknowledges the financial support from Academy of Finland(328933)Sigrid Juselius Foundation(28001830K1)Prof.H.A.Santos acknowledges the financial support from HiLIFE Research Funds and Sigrid Juselius Foundation.
文摘Immune cells play a crucial regulatory role in inflammatory phase and proliferative phase during skin healing.How to programmatically activate sequential immune responses is the key for scarless skin regeneration.In this study,an“Inner-Outer”IL-10-loaded electrospun fiber with cascade release behavior was constructed.During the inflammatory phase,the electrospun fiber released a lower concentration of IL-10 within the wound,inhibiting excessive recruitment of inflammatory cells and polarizing macrophages into anti-inflammatory phenotype“M2c”to suppress excessive inflammation response.During the proliferative phase,a higher concentration of IL-10 released by the fiber and the anti-fibrotic cytokines secreted by polarized“M2c”directly acted on dermal fibroblasts to simultaneously inhibit extracellular matrix overdeposition and promote fibroblast migration.The“Inner-Outer”IL-10-loaded electrospun fiber programmatically activated the sequential immune responses during wound healing and led to scarless skin regeneration,which is a promising immunomodulatory biomaterial with great potential for promoting complete tissue regeneration.
基金This work was financially supported by the Natural Science Foundation of China(81871472)Natural Science Foundation of Guangdong Province(Project No.2019A1515010696 and 2021A1515012333)+1 种基金Shenzhen Municipal Science,Technology and Innovation Commission(Project No.JCYJ20190807163003704)“100 Talents Program”of the start-up foundation from Sun Yat-sen University,Academy of Finland(328933)and Sigrid Jus´elius Foundation.
文摘Therapeutic oligonucleotides(TOs)represent one of the most promising drug candidates in the targeted cancer treatment due to their high specificity and capability of modulating cellular pathways that are not readily druggable.However,efficiently delivering of TOs to cancer cellular targets is still the biggest challenge in promoting their clinical translations.Emerging as a significant drug delivery vector,nanoparticles(NPs)can not only protect TOs from nuclease degradation and enhance their tumor accumulation,but also can improve the cell uptake efficiency of TOs as well as the following endosomal escape to increase the therapeutic index.Furthermore,targeted and on-demand drug release of TOs can also be approached to minimize the risk of toxicity towards normal tissues using stimuli-responsive NPs.In the past decades,remarkable progresses have been made on the TOs delivery based on various NPs with specific purposes.In this review,we will first give a brief introduction on the basis of TOs as well as the action mechanisms of several typical TOs,and then describe the obstacles that prevent the clinical translation of TOs,followed by a comprehensive overview of the recent progresses on TOs delivery based on several various types of nanocarriers containing lipid-based nanoparticles,polymeric nanoparticles,gold nanoparticles,porous nanoparticles,DNA/RNA nanoassembly,extracellular vesicles,and imaging-guided drug delivery nanoparticles.
基金the financial support of the National Natural Science Foundation of China(31771054,81871472,and 31830028)Academy of Finland Research Fellow(328933)+5 种基金Sigrid Jusélius Foundation grant(28002247k1)Natural Key Science Research Program of Jiangsu Provincial Department of Education(19KJA320006)National Key Research and Development Program of China(2016YFC1101600)Directive Project of Science and Technology Plan of Nantong City(MS12018028)226 High-Level Talent Training Project(2nd level,2018 II-182)of Nantong CityQinglan Project of Jiangsu Province(2018).
文摘Biofunctionalization of artificial nerve implants by incorporation of specific bioactive factors has greatly enhanced the success of grafting procedures for peripheral nerve regeneration.However,most studies on novel biofunctionalized implants have emphasized the promotion of neuronal and axonal repair over vascularization,a process critical for long-term functional restoration.We constructed a dual-biofunctionalized chitosan/collagen composite scaffold with Ile-Lys-Val-Ala-Val(IKVAV)and vascular endothelial growth factor(VEGF)by combining solution blending,in situ lyophilization,and surface biomodification.Immobilization of VEGF and IKVAV on the scaffolds was confirmed both qualitatively by staining and quantitatively by ELISA.Various single-and dual-biofunctionalized scaffolds were compared for the promotion of endothelial cell(EC)and Schwann cell(SC)proliferation as well as the induction of angiogenic and neuroregeneration-associated genes by these cells in culture.The efficacy of these scaffolds for vascularization was evaluated by implantation in chicken embryos,while functional repair capacity in vivo was assessed in rats subjected to a 10mm sciatic nerve injury.Dual-biofunctionalized scaffolds supported robust EC and SC proliferation and upregulated the expression levels of multiple genes and proteins related to neuroregeneration and vascularization.Dual-biofunctionalized scaffolds demonstrated superior vascularization induction in embryos and greater promotion of vascularization,myelination,and functional recovery in rats.These findings support the clinical potential of VEGF/IKVAV dual-biofunctionalized chitosan/collagen composite scaffolds for facilitating peripheral nerve regeneration,making it an attractive candidate for repairing critical nerve defect.The study may provide a critical experimental and theoretical basis for the development and design of new artificial nerve implants with excellent biological performance.
