Diabetic wounds are characterized by chronic inflammation,vascular insufficiency,and peripheral neuropathy,which collectively disrupt the neurovascular microenvironment essential for coordinated tissue regeneration.Ho...Diabetic wounds are characterized by chronic inflammation,vascular insufficiency,and peripheral neuropathy,which collectively disrupt the neurovascular microenvironment essential for coordinated tissue regeneration.However,strategies targeting neurovascular regeneration remain limited.Here,we developed a sprayable hydrogel sponge based on gelatin methacryloyl and methacrylamide-modifiedε-poly-L-lysine(S-GPL),cofunctionalized with VEGF-mimetic peptide(KLT)and BDNF-mimetic peptide(RGI).The sprayable format con-forms to irregular wound geometries,while the pneumatic spraying technique generates high-pressure micro-bubbles that create a porous structure,thereby enhancing exudate absorption and sustained peptide release as a sponge dressing.Additionally,the incorporation of KLT and RGI facilitates the reconstruction of the neuro-vascular microenvironment.In vitro,KLT promoted endothelial cell maturation and cytokine secretion,whereas RGI enhanced Schwann cell activity.Notably,S-GPL^(KLT/RGI) facilitated intercellular interactions between RSCs and HUVECs,highlighting the cellular mechanisms underlying neurovascular communication.In a full-thickness diabetic wound model in rats,the hydrogel accelerated wound closure,re-epithelialization,and matrix remodeling.These effects were accompanied by enhanced neovascularization and axonal regeneration,along with the formation of a spatially organized neurovascular niche,as evidenced by CD31^(+)capillaries closely aligned with PGP9.5^(+)nerve fibers.Building upon the intrinsic anti-inflammatory properties of S-GPL,tran-scriptomic and immunohistochemical analyses further revealed that S-GPL^(KLT/RGI) treatment suppressed the IL-17 signaling pathway.However,the relationship between immunomodulation and neurovascular reconstruction warrants further investigation.Collectively,this study presents a sprayable antibacterial hydrogel that not only reconstructs the neurovascular microenvironment but also mitigates chronic inflammation,offering a clinically translatable strategy for diabetic wound management.展开更多
Obesity driven by high-sugar and high-fat dietary patterns has become a major global health challenge and is closely associated with metabolic syndrome,diabetes,and cardiovascular disorders.Growing evidence indicates ...Obesity driven by high-sugar and high-fat dietary patterns has become a major global health challenge and is closely associated with metabolic syndrome,diabetes,and cardiovascular disorders.Growing evidence indicates that junk food disrupts lipid metabolism,alters gut microbiota,and triggers chronic inflammation,leading to systemic metabolic dysfunction.Traditional Chinese medicine(TCM),rooted in holistic regulation of organ systems,blood circulation,and energy balance,offers multi-target plant-based strategies for modulating obesity.This review summarizes key mechanisms through which Chinese medicinal plants counteract obesity,including appetite suppression,regulation of lipid metabolism,activation of thermogenesis,modulation of gut microbiota,and anti-oxidative and anti-inflammatory actions.Representative herbs such as Panax ginseng,Nelumbo nucifera,Cinnamomum cassia,Gynostemma pentaphyllum,and Pueraria lobata exhibit lipid-lowering,glucose-regulating,and inflammation-modulating activity in experimental and clinical studies.Overall,TCM herbal therapies provide a holistic and safe approach to correcting metabolic imbalance through multi-pathway regulation.However,standardized formulation,mechanistic validation,and large-scale clinical trials are urgently required to establish their efficacy and translational value.Future work integrating traditional knowledge with biomedical research will help position TCM-based phytotherapy as a scientifically grounded strategy for obesity prevention and management.展开更多
The immense complexity and interconnectedness of inflammation and metabolism in the primary tumor ecosystem and pre-metastatic niches(PMN)present an enormous challenge for developing advanced nanomedicines for cancer ...The immense complexity and interconnectedness of inflammation and metabolism in the primary tumor ecosystem and pre-metastatic niches(PMN)present an enormous challenge for developing advanced nanomedicines for cancer immunotherapy.Herein,an intelligent tumor-and PMN-tropic bioactive“nano-medfireman”(PsiL@M1M)was developed to not only arouse an appropriate photothermal immune cascade but also to“extinguish”the accompanying excessive inflammation.Ultimately,it aims to revitalize the immunosuppressive tumor microenvironment(TME)to spatiotemporally and effectively inhibit tumor metastasis and recurrence.PsiL@M1M was devised by incorporating the siRNA of lactate dehydrogenase A(siLDHA)on the functionalized photothermal mesoporous polydopamine(mPDA)and coupled with an M1-type macrophage membrane(M1M)to enable the capacity of inflammation targeting and modulation.PsiL@M1M actively accumulated and destroyed the primary tumor via photothermal therapy and subsequently mitigated the photothermal therapy-induced inflammatory cascade(e.g.,epithelial mesenchymal transition)via cytokine neutralization,eliminating the supply of tumor-derived secretory factors as“nutrients”for PMN.Concurrently,siLDHA interfered with lactate(LA)production,inhibited inflammation-LA communication and relieved immune checkpoint,thus profoundly reversing the immunosuppressive microenvironment of both the primary tumor and PMN.Through cooperation,PsiL@M1M initiated normalized hypo-inflammatory photo-immunotherapy against both local tumor growth and spontaneous metastasis/recurrence.Our study provides a paradigm for a new generation of photothermal nano-medicines for the whole process of tumor treatment.展开更多
Different outcomes of astrocyte inflammatory signalling in injury and neurodegeneration：It is emerging that astrocytes have a significant impact on the neuronal network by modulating synaptic connections and neuronal...Different outcomes of astrocyte inflammatory signalling in injury and neurodegeneration：It is emerging that astrocytes have a significant impact on the neuronal network by modulating synaptic connections and neuronal viability in both normal and pathological states.展开更多
基金supported by Beijing Natural Science Foundation of China(L254044,L244061,L244062,L234075)National Natural Sci-ence Foundation of China(82472565,82302828,32401140,32271414)+3 种基金Plastic Medicine Research Fund of Chinese Academy of Medical Sciences(2024-ZX-1-02,2024-ZX-1-03)National High Level Hospital Clinical Research Funding(2025-PUMCH-D-001,2022-PUMCH-C-025,2022-PUMCH-B-041,2022-PUMCH-A-025,2022-PUMCH-A-210)National Key R&D Program of China(2024YFC3405800,2024YFC3405801)Peking Union Medical Col-lege Hospital Talent Cultivation Program(Category C)No.UBJ11557.
文摘Diabetic wounds are characterized by chronic inflammation,vascular insufficiency,and peripheral neuropathy,which collectively disrupt the neurovascular microenvironment essential for coordinated tissue regeneration.However,strategies targeting neurovascular regeneration remain limited.Here,we developed a sprayable hydrogel sponge based on gelatin methacryloyl and methacrylamide-modifiedε-poly-L-lysine(S-GPL),cofunctionalized with VEGF-mimetic peptide(KLT)and BDNF-mimetic peptide(RGI).The sprayable format con-forms to irregular wound geometries,while the pneumatic spraying technique generates high-pressure micro-bubbles that create a porous structure,thereby enhancing exudate absorption and sustained peptide release as a sponge dressing.Additionally,the incorporation of KLT and RGI facilitates the reconstruction of the neuro-vascular microenvironment.In vitro,KLT promoted endothelial cell maturation and cytokine secretion,whereas RGI enhanced Schwann cell activity.Notably,S-GPL^(KLT/RGI) facilitated intercellular interactions between RSCs and HUVECs,highlighting the cellular mechanisms underlying neurovascular communication.In a full-thickness diabetic wound model in rats,the hydrogel accelerated wound closure,re-epithelialization,and matrix remodeling.These effects were accompanied by enhanced neovascularization and axonal regeneration,along with the formation of a spatially organized neurovascular niche,as evidenced by CD31^(+)capillaries closely aligned with PGP9.5^(+)nerve fibers.Building upon the intrinsic anti-inflammatory properties of S-GPL,tran-scriptomic and immunohistochemical analyses further revealed that S-GPL^(KLT/RGI) treatment suppressed the IL-17 signaling pathway.However,the relationship between immunomodulation and neurovascular reconstruction warrants further investigation.Collectively,this study presents a sprayable antibacterial hydrogel that not only reconstructs the neurovascular microenvironment but also mitigates chronic inflammation,offering a clinically translatable strategy for diabetic wound management.
文摘Obesity driven by high-sugar and high-fat dietary patterns has become a major global health challenge and is closely associated with metabolic syndrome,diabetes,and cardiovascular disorders.Growing evidence indicates that junk food disrupts lipid metabolism,alters gut microbiota,and triggers chronic inflammation,leading to systemic metabolic dysfunction.Traditional Chinese medicine(TCM),rooted in holistic regulation of organ systems,blood circulation,and energy balance,offers multi-target plant-based strategies for modulating obesity.This review summarizes key mechanisms through which Chinese medicinal plants counteract obesity,including appetite suppression,regulation of lipid metabolism,activation of thermogenesis,modulation of gut microbiota,and anti-oxidative and anti-inflammatory actions.Representative herbs such as Panax ginseng,Nelumbo nucifera,Cinnamomum cassia,Gynostemma pentaphyllum,and Pueraria lobata exhibit lipid-lowering,glucose-regulating,and inflammation-modulating activity in experimental and clinical studies.Overall,TCM herbal therapies provide a holistic and safe approach to correcting metabolic imbalance through multi-pathway regulation.However,standardized formulation,mechanistic validation,and large-scale clinical trials are urgently required to establish their efficacy and translational value.Future work integrating traditional knowledge with biomedical research will help position TCM-based phytotherapy as a scientifically grounded strategy for obesity prevention and management.
基金supported,in part or overall,by the National Natural Science Foundation of China(32171395,52372263,12132004,32471367)the Sichuan Science and Technology Program(2024NSFSC0601,2022NSFSC0048)the Program for Innovative Fundamental Research Incubation of UESTC(Y03023206100226).
文摘The immense complexity and interconnectedness of inflammation and metabolism in the primary tumor ecosystem and pre-metastatic niches(PMN)present an enormous challenge for developing advanced nanomedicines for cancer immunotherapy.Herein,an intelligent tumor-and PMN-tropic bioactive“nano-medfireman”(PsiL@M1M)was developed to not only arouse an appropriate photothermal immune cascade but also to“extinguish”the accompanying excessive inflammation.Ultimately,it aims to revitalize the immunosuppressive tumor microenvironment(TME)to spatiotemporally and effectively inhibit tumor metastasis and recurrence.PsiL@M1M was devised by incorporating the siRNA of lactate dehydrogenase A(siLDHA)on the functionalized photothermal mesoporous polydopamine(mPDA)and coupled with an M1-type macrophage membrane(M1M)to enable the capacity of inflammation targeting and modulation.PsiL@M1M actively accumulated and destroyed the primary tumor via photothermal therapy and subsequently mitigated the photothermal therapy-induced inflammatory cascade(e.g.,epithelial mesenchymal transition)via cytokine neutralization,eliminating the supply of tumor-derived secretory factors as“nutrients”for PMN.Concurrently,siLDHA interfered with lactate(LA)production,inhibited inflammation-LA communication and relieved immune checkpoint,thus profoundly reversing the immunosuppressive microenvironment of both the primary tumor and PMN.Through cooperation,PsiL@M1M initiated normalized hypo-inflammatory photo-immunotherapy against both local tumor growth and spontaneous metastasis/recurrence.Our study provides a paradigm for a new generation of photothermal nano-medicines for the whole process of tumor treatment.
文摘Different outcomes of astrocyte inflammatory signalling in injury and neurodegeneration：It is emerging that astrocytes have a significant impact on the neuronal network by modulating synaptic connections and neuronal viability in both normal and pathological states.
