Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,...Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,traditional chemotherapeutic drugs have many side effects and can easily lead to drug resistance in patients.The complex tumor microenvironment(TME) of MPE directly reduces the antitumor efficacy of immunotherapy.Fortunately,drug delivery systems(DDSs) based on biomaterials have the ability to overcome some of the drawbacks of conventional treatments by improving drug stability,increasing the accuracy of tumor cell targeting,reducing toxic side effects,and remodeling TME,ultimately improving drug efficacy.Therefore,the purpose of this review is to provide an overview and discussion of the latest progress in biomaterial-based DDSs for the treatment of MPE.We discuss the application of biomaterials in the treatment of MPE from multiple perspectives,including chemotherapy,immunotherapy,combination therapy,and pleurodesis,where microspheres,cell membrane-derived microparticles(MPs),micelles,nanoparticles,and liposomes,are involved.The application of these biomaterials has been proven to have great potential in the treatment of MPE,providing a new idea for follow-up research.展开更多
In recent years,different drugs therapies for treatment pulmonary fibrosis(PF) have gained much attention due to development of drug delivery technology and urgent clinical needs.PF treatment existed a variety of curr...In recent years,different drugs therapies for treatment pulmonary fibrosis(PF) have gained much attention due to development of drug delivery technology and urgent clinical needs.PF treatment existed a variety of currently clinical problem but PF could be treated with different drugs potentially though drug delivery technology.This review systematically expounds its basic theory,various drug delivery technologies,and future development directions.In the introduction,the relationship between the pathological mechanism of PF and drug delivery,the basic principles of the drug delivery system and the biological barriers faced by pulmonary drug delivery are analyzed.This review details delivery of small molecule drug,macromolecular drug and cells,including chemical synthesis and natural small molecule drug delivery,as well as RNA and cell-based delivery.Finally,the challenges and perspectives of these drugs to treat PF delivery technologies are discussed and key aspects in the development of PF drugs are considered.We hoped that this review can provide comprehensive and in-depth theoretical reference and technical support for the drug treatment of PF.展开更多
目的研究左归降糖解郁方调控模拟糖尿病并发抑郁症脑环境下的体外海马神经干细胞增殖与分化作用及分子机制。方法纯化和培养SD大鼠海马神经干细胞并通过标记巢蛋白(Nestin)进行荧光鉴定。取第3代海马神经干细胞进行实验,分为正常组、模...目的研究左归降糖解郁方调控模拟糖尿病并发抑郁症脑环境下的体外海马神经干细胞增殖与分化作用及分子机制。方法纯化和培养SD大鼠海马神经干细胞并通过标记巢蛋白(Nestin)进行荧光鉴定。取第3代海马神经干细胞进行实验,分为正常组、模型组、空白血清组、左归降糖解郁方含药血清组、左归降糖解郁方含药血清+海马无翅基因3a(recombinant wingless type MMTV integration site family member 3a,Wnt3a)信号抑制剂XAV-939组。在干细胞培养液中添加葡萄糖和皮质酮模拟糖尿病并发抑郁症脑环境进行造模,空白血清组和左归降糖解郁方含药血清组于造模同期分别给予不同血清。干预18 h后,采用WST-1检测干细胞活力,采用Brdu免疫荧光结合高内涵细胞成像技术评价干细胞的增殖能力,分别采用双皮质素(doublecortin,DCX)、胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)、神经元核抗原(neuron specific nuclear protein,NeuN)免疫荧光评估干细胞的分化能力,采用Western blotting检测各组细胞Wnt3a、低密度脂蛋白受体相关蛋白5(low density lipoprotein receptor-related protein 5,LRP5)、LRP6、β-连环蛋白(β-catenin)表达,采用qRTPCR法检测神经原素2(neurogenin 2,Ngn2)、细胞周期蛋白(cyclinD1)基因表达。结果左归降糖解郁方能显著增加受损海马神经干细胞的活力(P<0.01),增加Brdu、DCX、GFAP、NeuN的表达(P<0.01),增强其增殖和分化的能力。机制研究发现,左归降糖解郁方能显著增加神经干细胞中的Wnt3a、LRP5、LRP6、总β-catenin、核β-catenin蛋白的表达(P<0.05、0.01),激活Wnt3a信号并增加β-catenin的蓄积和入核,从而促进下游Ngn2、cyclinD1靶基因的转录(P<0.05、0.01)。XAV-939可通过增加β-catenin的降解(P<0.01),减少其进入细胞核,减少下游Ngn2、cyclinD1的m RNA转录(P<0.05、0.01),从而降低干细胞的增殖与分化能力。结论左归降糖解郁方能明显改善葡萄糖与皮质酮对体外海马神经干细胞增殖与分化的抑制作用,其改善作用与激活Wnt3a/β-catenin信号有关。展开更多
探讨柴金解郁安神片调控前扣带皮层(ACC)-腹侧海马(vHPC)谷氨酸能神经环路异常改善抑郁症大鼠腹侧海马神经元突触重塑的分子机制。首先运用化学遗传将谷氨酸能腺相关病毒(AAV)定位注射至大鼠ACC脑区,并通过慢性温和不可预知性应激(CUMS...探讨柴金解郁安神片调控前扣带皮层(ACC)-腹侧海马(vHPC)谷氨酸能神经环路异常改善抑郁症大鼠腹侧海马神经元突触重塑的分子机制。首先运用化学遗传将谷氨酸能腺相关病毒(AAV)定位注射至大鼠ACC脑区,并通过慢性温和不可预知性应激(CUMS)联合孤笼饲养复制大鼠抑郁模型,实验设正常组、模型组、AAV空载组、AAV病毒组、AAV病毒+糖皮质激素受体(GR)阻断剂组、AAV病毒+趋化因子受体1(CX3CR1)阻断剂组、AAV病毒+柴金解郁安神片组,采用水迷宫(Morris water maze)、旷场(open-field)和强迫游泳(forced-swimming)实验联合动物行为分析系统评估大鼠抑郁样行为;苏木素-伊红(HE)染色检测大鼠ACC及vHPC脑区神经元形态结构变化;免疫荧光及核磷酸蛋白(c-Fos)检测大鼠ACC-vHPC谷氨酸能神经环路激活情况;高尔基染色和透射电镜检测大鼠vHPC神经元树突、树突棘及突触亚微结构变化;免疫荧光、Western blot分别检测大鼠vHPC谷氨酸能神经元细胞内突触重塑相关蛋白谷氨酸受体2A(GRIN2A)、谷氨酸受体2B(GRIN2B)、Ca^(2+)/钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)、丝裂原激活蛋白激酶激活蛋白激酶2(MK2)、丝切蛋白(cofilin)表达水平。结果表明,谷氨酸能AAV病毒激活后模型组大鼠抑郁样行为表型、ACC及vHPC神经元形态结构、突触超微结构损伤更加加重,而GR、CX3CR1阻断剂均能不同程度逆转其异常改变,提示ACC脑区内胶质细胞GR/CX3CR1双信号介导的ACC-vHPC谷氨酸能神经环路异常激活可能与抑郁的发生发展密切相关。有趣的是,柴金解郁安神片也能显著抑制AAV病毒诱导的ACC-vHPC神经环路激活及Glu含量异常升高,同时有效逆转模型组大鼠进一步加重的抑郁样行为和vHPC谷氨酸能神经元突触重塑,并揭示其改善腹侧海马神经元突触损伤的分子机制可能与调控突触重塑相关信号NR/CaMKⅡ、MK2/cofilin有关。综上,该文证实了柴金解郁安神片能有效调控ACC-vHPC谷氨酸能神经环路异常进而改善抑郁症大鼠腹侧海马谷氨酸能神经元突触重塑,其分子机制可能与调节突触相关NR/CaMKⅡ、MK2/cofilin信号通路有关,这可能是其发挥抗抑郁作用的重要机制。展开更多
基金financial support from the Noncommunicable Chronic Diseases-National Science and Technology Major Project (Nos.2024ZD0522800,2024ZD0522803)the National Natural Science Foundation of China (Nos.U21A20417,31930067,31800797)+2 种基金the Natural Science Foundation of Sichuan Province (No.2024NSFSC0046)the Sichuan Science and Technology Program (No.2022YFS0333)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University (No.ZYGD24003)。
文摘Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,traditional chemotherapeutic drugs have many side effects and can easily lead to drug resistance in patients.The complex tumor microenvironment(TME) of MPE directly reduces the antitumor efficacy of immunotherapy.Fortunately,drug delivery systems(DDSs) based on biomaterials have the ability to overcome some of the drawbacks of conventional treatments by improving drug stability,increasing the accuracy of tumor cell targeting,reducing toxic side effects,and remodeling TME,ultimately improving drug efficacy.Therefore,the purpose of this review is to provide an overview and discussion of the latest progress in biomaterial-based DDSs for the treatment of MPE.We discuss the application of biomaterials in the treatment of MPE from multiple perspectives,including chemotherapy,immunotherapy,combination therapy,and pleurodesis,where microspheres,cell membrane-derived microparticles(MPs),micelles,nanoparticles,and liposomes,are involved.The application of these biomaterials has been proven to have great potential in the treatment of MPE,providing a new idea for follow-up research.
基金funded by the National Natural Science Foundation of China (No.NSFC82400096)Science and Technology Department of Sichuan Province (No.2025ZNSFSC1538)Xihua University Internal Talent Introduction Project with Scientific Research Funding (No.ZX20250087)。
文摘In recent years,different drugs therapies for treatment pulmonary fibrosis(PF) have gained much attention due to development of drug delivery technology and urgent clinical needs.PF treatment existed a variety of currently clinical problem but PF could be treated with different drugs potentially though drug delivery technology.This review systematically expounds its basic theory,various drug delivery technologies,and future development directions.In the introduction,the relationship between the pathological mechanism of PF and drug delivery,the basic principles of the drug delivery system and the biological barriers faced by pulmonary drug delivery are analyzed.This review details delivery of small molecule drug,macromolecular drug and cells,including chemical synthesis and natural small molecule drug delivery,as well as RNA and cell-based delivery.Finally,the challenges and perspectives of these drugs to treat PF delivery technologies are discussed and key aspects in the development of PF drugs are considered.We hoped that this review can provide comprehensive and in-depth theoretical reference and technical support for the drug treatment of PF.
文摘目的研究左归降糖解郁方调控模拟糖尿病并发抑郁症脑环境下的体外海马神经干细胞增殖与分化作用及分子机制。方法纯化和培养SD大鼠海马神经干细胞并通过标记巢蛋白(Nestin)进行荧光鉴定。取第3代海马神经干细胞进行实验,分为正常组、模型组、空白血清组、左归降糖解郁方含药血清组、左归降糖解郁方含药血清+海马无翅基因3a(recombinant wingless type MMTV integration site family member 3a,Wnt3a)信号抑制剂XAV-939组。在干细胞培养液中添加葡萄糖和皮质酮模拟糖尿病并发抑郁症脑环境进行造模,空白血清组和左归降糖解郁方含药血清组于造模同期分别给予不同血清。干预18 h后,采用WST-1检测干细胞活力,采用Brdu免疫荧光结合高内涵细胞成像技术评价干细胞的增殖能力,分别采用双皮质素(doublecortin,DCX)、胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)、神经元核抗原(neuron specific nuclear protein,NeuN)免疫荧光评估干细胞的分化能力,采用Western blotting检测各组细胞Wnt3a、低密度脂蛋白受体相关蛋白5(low density lipoprotein receptor-related protein 5,LRP5)、LRP6、β-连环蛋白(β-catenin)表达,采用qRTPCR法检测神经原素2(neurogenin 2,Ngn2)、细胞周期蛋白(cyclinD1)基因表达。结果左归降糖解郁方能显著增加受损海马神经干细胞的活力(P<0.01),增加Brdu、DCX、GFAP、NeuN的表达(P<0.01),增强其增殖和分化的能力。机制研究发现,左归降糖解郁方能显著增加神经干细胞中的Wnt3a、LRP5、LRP6、总β-catenin、核β-catenin蛋白的表达(P<0.05、0.01),激活Wnt3a信号并增加β-catenin的蓄积和入核,从而促进下游Ngn2、cyclinD1靶基因的转录(P<0.05、0.01)。XAV-939可通过增加β-catenin的降解(P<0.01),减少其进入细胞核,减少下游Ngn2、cyclinD1的m RNA转录(P<0.05、0.01),从而降低干细胞的增殖与分化能力。结论左归降糖解郁方能明显改善葡萄糖与皮质酮对体外海马神经干细胞增殖与分化的抑制作用,其改善作用与激活Wnt3a/β-catenin信号有关。
文摘探讨柴金解郁安神片调控前扣带皮层(ACC)-腹侧海马(vHPC)谷氨酸能神经环路异常改善抑郁症大鼠腹侧海马神经元突触重塑的分子机制。首先运用化学遗传将谷氨酸能腺相关病毒(AAV)定位注射至大鼠ACC脑区,并通过慢性温和不可预知性应激(CUMS)联合孤笼饲养复制大鼠抑郁模型,实验设正常组、模型组、AAV空载组、AAV病毒组、AAV病毒+糖皮质激素受体(GR)阻断剂组、AAV病毒+趋化因子受体1(CX3CR1)阻断剂组、AAV病毒+柴金解郁安神片组,采用水迷宫(Morris water maze)、旷场(open-field)和强迫游泳(forced-swimming)实验联合动物行为分析系统评估大鼠抑郁样行为;苏木素-伊红(HE)染色检测大鼠ACC及vHPC脑区神经元形态结构变化;免疫荧光及核磷酸蛋白(c-Fos)检测大鼠ACC-vHPC谷氨酸能神经环路激活情况;高尔基染色和透射电镜检测大鼠vHPC神经元树突、树突棘及突触亚微结构变化;免疫荧光、Western blot分别检测大鼠vHPC谷氨酸能神经元细胞内突触重塑相关蛋白谷氨酸受体2A(GRIN2A)、谷氨酸受体2B(GRIN2B)、Ca^(2+)/钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)、丝裂原激活蛋白激酶激活蛋白激酶2(MK2)、丝切蛋白(cofilin)表达水平。结果表明,谷氨酸能AAV病毒激活后模型组大鼠抑郁样行为表型、ACC及vHPC神经元形态结构、突触超微结构损伤更加加重,而GR、CX3CR1阻断剂均能不同程度逆转其异常改变,提示ACC脑区内胶质细胞GR/CX3CR1双信号介导的ACC-vHPC谷氨酸能神经环路异常激活可能与抑郁的发生发展密切相关。有趣的是,柴金解郁安神片也能显著抑制AAV病毒诱导的ACC-vHPC神经环路激活及Glu含量异常升高,同时有效逆转模型组大鼠进一步加重的抑郁样行为和vHPC谷氨酸能神经元突触重塑,并揭示其改善腹侧海马神经元突触损伤的分子机制可能与调控突触重塑相关信号NR/CaMKⅡ、MK2/cofilin有关。综上,该文证实了柴金解郁安神片能有效调控ACC-vHPC谷氨酸能神经环路异常进而改善抑郁症大鼠腹侧海马谷氨酸能神经元突触重塑,其分子机制可能与调节突触相关NR/CaMKⅡ、MK2/cofilin信号通路有关,这可能是其发挥抗抑郁作用的重要机制。
