Consumers are increasingly demanding natural colorants that are safe and offer health benefits.In addition to their ornamental characteristics,Kanzan cherry(KC)blossoms present a promising source of red-hued natural c...Consumers are increasingly demanding natural colorants that are safe and offer health benefits.In addition to their ornamental characteristics,Kanzan cherry(KC)blossoms present a promising source of red-hued natural colorants and functional bioactive substances.This research utilized distilled water to extract KC petals(KCP)and their ground powders(KCPP)under varying temperatures(30℃–90℃)and times(30–180 min).The total monomeric anthocyanins(TMAC)and total phenolics(TPC)in the extracts were evaluated via the pH differential and Folin–Ciocalteu methods.Antioxidant capacities were assessed by DPPH free radical scavenging ability and reducing power.Results indicated that the optimal extraction of TMAC and TPC from KCP occurred at 90℃ for 30 min,and the resulting extracts exhibited the highest antioxidant activities among all tested temperatures and durations.Compared to different particle sizes,the finest KCPP generally produced extracts with the highest TMAC,TPC,and antioxidant activity,due to enhanced mass and heat transfer.When compared with the acidified alcohol method,hot water extraction resulted in 68.23%and 71.41%TMAC yields for petals and powders,respectively,while TPC levels were similar or higher.TMAC or TPC showed a significantly positive correlation(p<0.01)with the antioxidant activities.These findings demonstrate that hot water extraction is a viable and environmentally friendly alternative for phytochemical recovery from KC.Additionally,elevated extraction temperature and pH accelerated anthocyanin degradation and shortened its half-life,while higher pH also lowered the activation energy,enthalpy,entropy,and Gibbs free energy.Thus,red–orange KC extracts with rich bioactivity may serve as promising ingredients for functional foods having acidic pH levels.展开更多
Tumor metastasis is the leading cause of high mortality in most cancers,and numerous studies have demonstrated that the malignant crosstalk of multiple components in the tumor microenvironment(TME)together promotes tu...Tumor metastasis is the leading cause of high mortality in most cancers,and numerous studies have demonstrated that the malignant crosstalk of multiple components in the tumor microenvironment(TME)together promotes tumor metastasis.Cancer-associated fibroblasts(CAFs)are the major stromal cells and crosstalk centers in the TME of various kinds of tumors,such as breast cancer,pancreatic cancer,and prostate cancer.Recently,the CAF-induced pro-tumor metastatic TME has gained wide attention,being considered as one of the effective targets for tumor therapy.With in-depth research,CAFs have been found to promote tumor metastasis through multiple mechanisms,such as inducing epithelial emesenchymal transition in tumor cells,remodeling the extracellular matrix,protecting circulating tumor cells,and facilitating the formation of a pre-metastatic niche.To enhance the anti-tumor metastasis effect,therapeutic strategies designed by combining nano-drug delivery systems with CAF modulation are undoubtedly a desirable choice,as evidenced by the research over the past decades.Herein,we introduce the physiological properties of CAFs,detail the possible mechanisms whereby CAFs promote tumor metastasis,categorize CAFs-based nano-drug delivery strategies according to their anti-metastasis functions and discuss the current challenges,possible solutions,as well as the future directions in order to provide a theoretical basis and reference for the utilization of CAFs-based nano-drug delivery strategies to promote tumor metastasis therapy.展开更多
Immunotherapy of triple-negative breast cancer(TNBC)is significantly hindered by the immunosuppressive tumor microenvironment(TME).Notably,tumor-associated macrophages(TAMs),which constitute the predominant infiltrati...Immunotherapy of triple-negative breast cancer(TNBC)is significantly hindered by the immunosuppressive tumor microenvironment(TME).Notably,tumor-associated macrophages(TAMs),which constitute the predominant infiltrating immune cell type in TNBC,represent a critical target for“turning off”immunosuppressive TME.Despite numerous ongoing clinical trials,current strategies exhibit limited efficacy in overcoming immunosuppressive TME.Interestingly,regulation of son of sevenless 1(SOS1),which is overexpressed in TNBC patients,shows promising potential for TAM repolarization.Herein,we developed a biomimetic liposomal platform(CCM/Cil-lipo@TD),which integrates cilengitide(Cil)-functionalized breast cancer cell membranes(CCM)to co-deliver tetrandrine(TET)and low-dose docetaxel(DTX)for TNBC therapy.This system synergistically enhanced immunotherapy by coupling SOS1 blockade-driven TAM repolarization with immune cell death(ICD)-mediated dendritic cell(DC)maturation,thereby reshaping the highly immunosuppressive TME in TNBC.Critically,the low-density Cil-anchored,CCM-fused liposomes overcome the penetration limitations inherent to conventional CCM-based delivery systems,achieving deep intratumoral accumulation of therapeutic payloads.Mechanistically,the CCM/Cil-lipo@TD ensured that TET-mediated SOS1 inhibition in tumor cells efficiently polarized TAM2(protumor)toward TAM1(antitumor).Furthermore,SOS1 blockade synergized with low-dose DTX-induced ICD to remodel TME,as evidenced by sustained cytotoxic T-cell infiltration and suppression of regulatory T cells.The CCM/Cil-lipo@TD exerted superior tumor inhibition(82.9%)in 4T1 orthotopic models and effectively inhibited postoperative local recurrence and distant metastasis.Taken together,the Cil-engineered,cellmembrane-anchoring CCM/Cil-lipo@TD provides a promising approach for TNBC immunotherapy.展开更多
基金funded by the Research Fund(Project Number 2025YB12)Innovation and Entrepreneurship Project(2024)of Shanghai Sanda University.
文摘Consumers are increasingly demanding natural colorants that are safe and offer health benefits.In addition to their ornamental characteristics,Kanzan cherry(KC)blossoms present a promising source of red-hued natural colorants and functional bioactive substances.This research utilized distilled water to extract KC petals(KCP)and their ground powders(KCPP)under varying temperatures(30℃–90℃)and times(30–180 min).The total monomeric anthocyanins(TMAC)and total phenolics(TPC)in the extracts were evaluated via the pH differential and Folin–Ciocalteu methods.Antioxidant capacities were assessed by DPPH free radical scavenging ability and reducing power.Results indicated that the optimal extraction of TMAC and TPC from KCP occurred at 90℃ for 30 min,and the resulting extracts exhibited the highest antioxidant activities among all tested temperatures and durations.Compared to different particle sizes,the finest KCPP generally produced extracts with the highest TMAC,TPC,and antioxidant activity,due to enhanced mass and heat transfer.When compared with the acidified alcohol method,hot water extraction resulted in 68.23%and 71.41%TMAC yields for petals and powders,respectively,while TPC levels were similar or higher.TMAC or TPC showed a significantly positive correlation(p<0.01)with the antioxidant activities.These findings demonstrate that hot water extraction is a viable and environmentally friendly alternative for phytochemical recovery from KC.Additionally,elevated extraction temperature and pH accelerated anthocyanin degradation and shortened its half-life,while higher pH also lowered the activation energy,enthalpy,entropy,and Gibbs free energy.Thus,red–orange KC extracts with rich bioactivity may serve as promising ingredients for functional foods having acidic pH levels.
基金the National Natural Science Foundation of China(Grant No.82274281,81773909)“Shuguang Program”supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission(22SG41,China)+1 种基金Shanghai Talent Development Funds(Grant No.201665,China)the combination of the medical care and health project of the Shanghai University of Traditional Chinese Medicine(YYKC‒2021‒01‒008,China).
文摘Tumor metastasis is the leading cause of high mortality in most cancers,and numerous studies have demonstrated that the malignant crosstalk of multiple components in the tumor microenvironment(TME)together promotes tumor metastasis.Cancer-associated fibroblasts(CAFs)are the major stromal cells and crosstalk centers in the TME of various kinds of tumors,such as breast cancer,pancreatic cancer,and prostate cancer.Recently,the CAF-induced pro-tumor metastatic TME has gained wide attention,being considered as one of the effective targets for tumor therapy.With in-depth research,CAFs have been found to promote tumor metastasis through multiple mechanisms,such as inducing epithelial emesenchymal transition in tumor cells,remodeling the extracellular matrix,protecting circulating tumor cells,and facilitating the formation of a pre-metastatic niche.To enhance the anti-tumor metastasis effect,therapeutic strategies designed by combining nano-drug delivery systems with CAF modulation are undoubtedly a desirable choice,as evidenced by the research over the past decades.Herein,we introduce the physiological properties of CAFs,detail the possible mechanisms whereby CAFs promote tumor metastasis,categorize CAFs-based nano-drug delivery strategies according to their anti-metastasis functions and discuss the current challenges,possible solutions,as well as the future directions in order to provide a theoretical basis and reference for the utilization of CAFs-based nano-drug delivery strategies to promote tumor metastasis therapy.
基金funded by“Shuguang Program”supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission(22SG41)the combination of the medical care and health project of the Shanghai University of Traditional Chinese Medicine(YYKC-2021-01-008).
文摘Immunotherapy of triple-negative breast cancer(TNBC)is significantly hindered by the immunosuppressive tumor microenvironment(TME).Notably,tumor-associated macrophages(TAMs),which constitute the predominant infiltrating immune cell type in TNBC,represent a critical target for“turning off”immunosuppressive TME.Despite numerous ongoing clinical trials,current strategies exhibit limited efficacy in overcoming immunosuppressive TME.Interestingly,regulation of son of sevenless 1(SOS1),which is overexpressed in TNBC patients,shows promising potential for TAM repolarization.Herein,we developed a biomimetic liposomal platform(CCM/Cil-lipo@TD),which integrates cilengitide(Cil)-functionalized breast cancer cell membranes(CCM)to co-deliver tetrandrine(TET)and low-dose docetaxel(DTX)for TNBC therapy.This system synergistically enhanced immunotherapy by coupling SOS1 blockade-driven TAM repolarization with immune cell death(ICD)-mediated dendritic cell(DC)maturation,thereby reshaping the highly immunosuppressive TME in TNBC.Critically,the low-density Cil-anchored,CCM-fused liposomes overcome the penetration limitations inherent to conventional CCM-based delivery systems,achieving deep intratumoral accumulation of therapeutic payloads.Mechanistically,the CCM/Cil-lipo@TD ensured that TET-mediated SOS1 inhibition in tumor cells efficiently polarized TAM2(protumor)toward TAM1(antitumor).Furthermore,SOS1 blockade synergized with low-dose DTX-induced ICD to remodel TME,as evidenced by sustained cytotoxic T-cell infiltration and suppression of regulatory T cells.The CCM/Cil-lipo@TD exerted superior tumor inhibition(82.9%)in 4T1 orthotopic models and effectively inhibited postoperative local recurrence and distant metastasis.Taken together,the Cil-engineered,cellmembrane-anchoring CCM/Cil-lipo@TD provides a promising approach for TNBC immunotherapy.
