Neuroinflammation plays a significant role in inducing depression-like behavior. Tetrahedral DNA nanostructures(TDNs) are molecules that exhibit anti-inflammatory properties and can effectively penetrate the blood-bra...Neuroinflammation plays a significant role in inducing depression-like behavior. Tetrahedral DNA nanostructures(TDNs) are molecules that exhibit anti-inflammatory properties and can effectively penetrate the blood-brain barrier. Thus, researchers have hypothesized that TDNs regulate the secretion of proinflammatory cytokines and consequently alleviate depression-like behavior. To test this hypothesis, we investigated the effect of TDNs on the depression-like behavior of C57 mice induced by lipopolysaccharide(LPS). We performed open-field, tail suspension, and sucrose preference tests on LPS-and LPS/TDNtreated mice. The results indicated that the injection of TDNs into LPS-treated mice resulted in increased velocity, center zone duration, frequency to the center zone, and sucrose preference, and decreased immobility time. Immunofluorescence results indicated that peripheral administration of LPS in the mice activated inflammation, which culminated in distinct depression-like behavior. However, TDNs effectively alleviated the inflammation and depression-like behavior through the reduction of the expression levels of proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α in the brain. Additionally, TDNs normalized the expression level of microglia cell activation markers, such as ionized calcium binding adaptor molecule 1, in the hippocampus of mice. These results indicated that TDNs attenuated the LPS-induced secretion of inflammatory factors and consequently alleviated depression-like behavior.展开更多
Gouty arthritis is a very familiar inflammatory arthritis.Controlling inflammation is the key to preventing gouty arthritis.However,colchicine,the most highly represented drug used in clinical practice,has strict cont...Gouty arthritis is a very familiar inflammatory arthritis.Controlling inflammation is the key to preventing gouty arthritis.However,colchicine,the most highly represented drug used in clinical practice,has strict contraindications owing to some severe side effects.Curcumin(Cur),a natural anti-inflammatory drug,has demonstrated good safety and efficacy.However,the rapid degradation,poor aqueous solubility,and low bioavailability of Cur limit its therapeutic effect.To strengthen the effectiveness and bioavailability of Cur.Cur loaded tetrahedral framework nucleic acids(Cur-TFNAs)were synthesized to deliver Cur.Compared with free Cur,Cur-TFNAs exhibit a preferable drug stability,good biocompatibility(CCK-8 assay),ease of uptake(immunofluorescence),and higher tissue utilization(in vivo biodistribution).Most importantly,Cur-TFNAs present better anti-inflammatory effect than free Cur both in vivo and in vitro experiments through the determination of inflammation-related cytokines expression.Therefore,we believe that Cur-TFNAs have great prospects for the prevention of gout and similar inflammatory diseases.展开更多
While the skin is considered the first line of defense in the human body,there are some vulnerabilities that render it susceptible to certain threats,which is an issue that is recognized by both patients and doctors.C...While the skin is considered the first line of defense in the human body,there are some vulnerabilities that render it susceptible to certain threats,which is an issue that is recognized by both patients and doctors.Cutaneous wound healing is a series of complex processes that involve many types of cells,such as fibroblasts and keratinocytes.This study showed that tetrahedral framework nucleic acids(tFNAs),a type of self-assembled nucleic-acid material,have the ability to promote keratinocyte(HaCaT cell line)and fibroblast(HSF cell line)proliferation and migration in vitro.In addition,tFNAs increased the secretion of vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)in HSF cells and reduced the production of tumor necrosis factor-alpha(TNF-α)and interleukin-1 beta(IL-1β)in HaCaT cells by activating the AKT-signaling pathway.During in vivo experiments,tFNA treatments accelerated the healing process in skin wounds and decreased the development of scars,compared with the control treatment that did not use tFNAs.This is the first study to demonstrate that nanophase materials with the biological features of nucleic acids accelerate the healing of cutaneous wounds and reduce scarring,which indicates the potential application of tFNAs in skin tissue regeneration.展开更多
Parkinson’s disease(PD)is one of the most prevalent neurodegenerative diseases.It is usually accompanied by motor and non-motor symptoms that seriously threaten the health and the quality of life.Novel medications ar...Parkinson’s disease(PD)is one of the most prevalent neurodegenerative diseases.It is usually accompanied by motor and non-motor symptoms that seriously threaten the health and the quality of life.Novel medications are urgently needed because current pharmaceuticals can relieve symptoms but cannot stop disease progression.The microbiota-gut-brain axis(MGBA)is closely associated with the occurrence and development of PD and is an effective therapeutic target.Tetrahedral framework nucleic acids(tFNAs)can modulate the microbiome and immune regulation.However,such nucleic acid nanostructures are very sensitive to acids which hinder this promising approach.Therefore,we prepared exosome-like nanovesicles(Exo@tac)from ginger that are acid resistant and equipped with tFNAs modified by antimicrobial peptides(AMP).We verified that Exo@tac regulates intestinal bacteria associated with the microbial-gut-brain axis in vitro and significantly improves PD symptoms in vivo when administered orally.Microbiota profiling confirmed that Exo@tac normalizes the intestinal flora composition of mouse models of PD.Our findings present a novel strategy for the development of PD drugs and the innovative delivery of nucleic acid nanomedicines.展开更多
Tetrahedral DNA nanostructures(TDNs)are molecules with a pyramidal structure formed by folding four single strands of DNA based on the principle of base pairing.Although DNA has polyanionic properties,the special spat...Tetrahedral DNA nanostructures(TDNs)are molecules with a pyramidal structure formed by folding four single strands of DNA based on the principle of base pairing.Although DNA has polyanionic properties,the special spatial structure of TDNs allows them to penetrate the cell membrane without the aid of transfection agents in a caveolin-dependent manner and enables them to participate in the regulation of cellular processes without obvious toxic side effects.Because of their stable spatial structure,TDNs resist the limitations imposed by nuclease activity and innate immune responses to DNA.In addition,TDNs have good editability and biocompatibility,giving them great advantages for biomedical applications.Previous studies have found that TDNs have a variety of biological properties,including promoting cell migration,proliferation and differentiation,as well as having anti-inflammatory,antioxidant,anti-infective and immune regulation capabilities.Moreover,we confirmed that TDNs can promote the regeneration and repair of skin,blood vessels,muscles and bone tissues.Based on these findings,we believe that TDNs have broad prospects for application in wound repair and regeneration.This article reviews recent progress in TDN research and its applications.展开更多
基金supported by the National Key R&D Program of China (No. 2019YFA0110600)the National Natural Science Foundation of China (Nos. 82001432, 81970916)+1 种基金the China Postdoctoral Science Foundation (Nos. 2020TQ0213, 2020M683319)the West China Hospital Postdoctoral Science Foundation (No.2020HXBH104)。
文摘Neuroinflammation plays a significant role in inducing depression-like behavior. Tetrahedral DNA nanostructures(TDNs) are molecules that exhibit anti-inflammatory properties and can effectively penetrate the blood-brain barrier. Thus, researchers have hypothesized that TDNs regulate the secretion of proinflammatory cytokines and consequently alleviate depression-like behavior. To test this hypothesis, we investigated the effect of TDNs on the depression-like behavior of C57 mice induced by lipopolysaccharide(LPS). We performed open-field, tail suspension, and sucrose preference tests on LPS-and LPS/TDNtreated mice. The results indicated that the injection of TDNs into LPS-treated mice resulted in increased velocity, center zone duration, frequency to the center zone, and sucrose preference, and decreased immobility time. Immunofluorescence results indicated that peripheral administration of LPS in the mice activated inflammation, which culminated in distinct depression-like behavior. However, TDNs effectively alleviated the inflammation and depression-like behavior through the reduction of the expression levels of proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α in the brain. Additionally, TDNs normalized the expression level of microglia cell activation markers, such as ionized calcium binding adaptor molecule 1, in the hippocampus of mice. These results indicated that TDNs attenuated the LPS-induced secretion of inflammatory factors and consequently alleviated depression-like behavior.
基金funded by the National Key R&D Program of China[2019YFA0110600]National Natural Science Foundation of China[81970916,81671031].
文摘Gouty arthritis is a very familiar inflammatory arthritis.Controlling inflammation is the key to preventing gouty arthritis.However,colchicine,the most highly represented drug used in clinical practice,has strict contraindications owing to some severe side effects.Curcumin(Cur),a natural anti-inflammatory drug,has demonstrated good safety and efficacy.However,the rapid degradation,poor aqueous solubility,and low bioavailability of Cur limit its therapeutic effect.To strengthen the effectiveness and bioavailability of Cur.Cur loaded tetrahedral framework nucleic acids(Cur-TFNAs)were synthesized to deliver Cur.Compared with free Cur,Cur-TFNAs exhibit a preferable drug stability,good biocompatibility(CCK-8 assay),ease of uptake(immunofluorescence),and higher tissue utilization(in vivo biodistribution).Most importantly,Cur-TFNAs present better anti-inflammatory effect than free Cur both in vivo and in vitro experiments through the determination of inflammation-related cytokines expression.Therefore,we believe that Cur-TFNAs have great prospects for the prevention of gout and similar inflammatory diseases.
基金supported by the National Key R&D Program of China(2019YFA0110600)the National Natural Science Foundation of China(81970916,81671031).
文摘While the skin is considered the first line of defense in the human body,there are some vulnerabilities that render it susceptible to certain threats,which is an issue that is recognized by both patients and doctors.Cutaneous wound healing is a series of complex processes that involve many types of cells,such as fibroblasts and keratinocytes.This study showed that tetrahedral framework nucleic acids(tFNAs),a type of self-assembled nucleic-acid material,have the ability to promote keratinocyte(HaCaT cell line)and fibroblast(HSF cell line)proliferation and migration in vitro.In addition,tFNAs increased the secretion of vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)in HSF cells and reduced the production of tumor necrosis factor-alpha(TNF-α)and interleukin-1 beta(IL-1β)in HaCaT cells by activating the AKT-signaling pathway.During in vivo experiments,tFNA treatments accelerated the healing process in skin wounds and decreased the development of scars,compared with the control treatment that did not use tFNAs.This is the first study to demonstrate that nanophase materials with the biological features of nucleic acids accelerate the healing of cutaneous wounds and reduce scarring,which indicates the potential application of tFNAs in skin tissue regeneration.
基金supported by the National Natural Science Foundation of China(82370929 and 82401144)Sichuan Science and Technology Program(2022NSFSC0002)+3 种基金Sichuan Province Youth Science and Technology Innovation Team(2022JDTD0021)Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD03202302 and RCDWJS2024-1)China Postdoctoral Science Foundation(CPSF)(2024M752238)Postdoctoral Fellowship Program of CPSF(GZC20231787).
文摘Parkinson’s disease(PD)is one of the most prevalent neurodegenerative diseases.It is usually accompanied by motor and non-motor symptoms that seriously threaten the health and the quality of life.Novel medications are urgently needed because current pharmaceuticals can relieve symptoms but cannot stop disease progression.The microbiota-gut-brain axis(MGBA)is closely associated with the occurrence and development of PD and is an effective therapeutic target.Tetrahedral framework nucleic acids(tFNAs)can modulate the microbiome and immune regulation.However,such nucleic acid nanostructures are very sensitive to acids which hinder this promising approach.Therefore,we prepared exosome-like nanovesicles(Exo@tac)from ginger that are acid resistant and equipped with tFNAs modified by antimicrobial peptides(AMP).We verified that Exo@tac regulates intestinal bacteria associated with the microbial-gut-brain axis in vitro and significantly improves PD symptoms in vivo when administered orally.Microbiota profiling confirmed that Exo@tac normalizes the intestinal flora composition of mouse models of PD.Our findings present a novel strategy for the development of PD drugs and the innovative delivery of nucleic acid nanomedicines.
基金supported by the National Key R&D Program of China(No.2019YFA0110600)National Natural Science Foundation of China(Nos.82001432,81970916)+1 种基金China Postdoctoral Science Foundation(Nos.2020TQ0213,2020 M683319)West China Hospital Postdoctoral Science Foundation(No.2020HXBH104).
文摘Tetrahedral DNA nanostructures(TDNs)are molecules with a pyramidal structure formed by folding four single strands of DNA based on the principle of base pairing.Although DNA has polyanionic properties,the special spatial structure of TDNs allows them to penetrate the cell membrane without the aid of transfection agents in a caveolin-dependent manner and enables them to participate in the regulation of cellular processes without obvious toxic side effects.Because of their stable spatial structure,TDNs resist the limitations imposed by nuclease activity and innate immune responses to DNA.In addition,TDNs have good editability and biocompatibility,giving them great advantages for biomedical applications.Previous studies have found that TDNs have a variety of biological properties,including promoting cell migration,proliferation and differentiation,as well as having anti-inflammatory,antioxidant,anti-infective and immune regulation capabilities.Moreover,we confirmed that TDNs can promote the regeneration and repair of skin,blood vessels,muscles and bone tissues.Based on these findings,we believe that TDNs have broad prospects for application in wound repair and regeneration.This article reviews recent progress in TDN research and its applications.
