Glioblastoma is acknowledged as the most aggressive cerebral tumor in adults.However,the efficacy of current standard therapy is seriously undermined by drug resistance and suppressive immune microenvironment.Ferropto...Glioblastoma is acknowledged as the most aggressive cerebral tumor in adults.However,the efficacy of current standard therapy is seriously undermined by drug resistance and suppressive immune microenvironment.Ferroptosis is a recently discovered form of iron-dependent cell death that may have excellent prospect as chemosensitizer.The utilization of ferropotosis inducer Erastin could significantly mediate chemotherapy sensitization of Temozolomide and exert anti-tumor effects in glioblastoma.In this study,a combination of hydrogel-liposome nanoplatform encapsulatedwith Temozolomide and ferroptosis inducer Erastin was constructed.Theαvβ3 integrin-binding peptide cyclic RGD was utilized to modify codelivery system to achieve glioblastoma targeting strategy.As biocompatible drug reservoirs,cross-linked GelMA(gelatin methacrylamide)hydrogel and cRGD-coated liposome realized the sustained release of internal contents.In the modified intracranial tumor resection model,GelMA-liposome system achieved slow release of Temozolomide and Erastin in situ for more than 14 d.The results indicated that nanoplatform(T+E@LPs-cRGD+GelMA)improved glioblastoma sensitivity to chemotherapeutic temozolomide and exerted satisfactory anti-tumor effects.It was demonstrated that the induction of ferroptosis could be utilized as a therapeutic strategy to overcome drug resistance.Furthermore,transcriptome sequencing was conducted to reveal the underlying mechanism that the nanoplatform(T+E@LPs-cRGD+GelMA)implicated in.It is suggested that GelMA-liposome system participated in the immune response and immunomodulation of glioblastoma via interferon/PD-L1 pathway.Collectively,this study proposed a potential combinatory therapeutic strategy for glioblastoma treatment.展开更多
AIM: To explore the feasibility of using hypericin as an optical imaging probe with affinity for cholesterol for differential fluorescent detection of human gallstones.METHODS: Cholesterol, mixed and pigment stones fr...AIM: To explore the feasibility of using hypericin as an optical imaging probe with affinity for cholesterol for differential fluorescent detection of human gallstones.METHODS: Cholesterol, mixed and pigment stones from cholecystectomy patients were incubated with hypericin or solvent. After 72 h, the stones were analysed for fluorescence(365 nm) and treated with 2-propanol/dimethyl sulfoxide for high performance liquid chromatography(HPLC) analysis. Rats with virtual gallbladder containing human cholesterol, mixed or pigment gallstones(VGHG) received 5 mg/kg hypericin or solvent and VGHG rats with cholesterol stones were given different hypericin doses(5-15 mg/kg). Twelve hours later, the stones were analysed at 365 nm. Biliary excretion and metabolites of hypericin were assessed in common bile duct(CBD) cannulated rats for 9 h using fluorospectrometry, HPLC and matrixassisted laser desorption/ionization-time-of-flight mass spectrometry(MALDI-TOF MS).RESULTS: Homogeneous high fluorescence was seen on cholesterol stones either pre-incubated with hypericin or extracted from VGHG rats receiving hypericin. Mixed stones showed a dotted fluorescent pattern, whereas pigment and solvent-treated ones lacked fluorescence. HPLC showed 7.68, 6.65 and 0.08 × 10^(-3) M of cholesterol in extracts from cholesterol, mixed, and pigment gallstones, respectively. Hypericin accounted for 2.0, 0.5 and 0.2 × 10-6 M in that order. On cholesterol stones from VGHG rats receiving different hypericin doses, a positive correlation was observed between dose and fluorescence. In the bile from CBD-cannulated rats, fluorescence represented 20% of the injected dose with two peaks in 9 h. HPLC analysis revealed that hypericin conjugates reached 60% of the peak area. By MALDI-TOF MS, hypericinglucuronide was detected. CONCLUSION: This study proves the potential use of hypericin for differential fluorescent detection of human gallstones regarding their chemical composition.展开更多
Radular teeth of chitons were studied by using magnetic torque-meter and transmission electron microscopy (TEM). The magnetic torque curves give clear evidence of presence of strong uni-axial magnetic anisotropy. The ...Radular teeth of chitons were studied by using magnetic torque-meter and transmission electron microscopy (TEM). The magnetic torque curves give clear evidence of presence of strong uni-axial magnetic anisotropy. The easy axis is along the length direction of tongue-like radula. The TEM pattern shows that long chip-like magnetite nano-scaled particles packed in the radular teeth with both uni-axial shape anisotropy and magneto-crystalline anisotropy.展开更多
Premature ovarian failure refers to a disease in which women usually present with amenorrhea,infertility,decreased estrogen secretion,and increased gonadotropin before the age of 40.It seriously endangers women’s hea...Premature ovarian failure refers to a disease in which women usually present with amenorrhea,infertility,decreased estrogen secretion,and increased gonadotropin before the age of 40.It seriously endangers women’s health,making them prone to various endocrine reproductive and even systemic disorders.Its pathogenesis remains unclear;however,it may be related to genetic,immune,enzyme deficiency,iatrogenic,cyclin,psychology,and other factors.Traditional Chinese medicine believes that its etiology is related to the kidney,liver,and spleen.It can be divided into kidney deficiency and liver depression syndrome,liver and kidney Yin deficiency syndrome,spleen and kidney Yang deficiency syndrome,and so on.Traditional Chinese medicine is mainly made up of oral Chinese medicine,acupuncture,and other therapies.Through literature research,this paper discusses the etiology,pathological mechanism,and treatment of premature ovarian failure in the field of traditional Chinese medicine.展开更多
Serving as targeting ligands,aptamers have shown promise in precision medicine.However,the lack of knowledge of the biosafety and metabolism patterns in the human body largely impeded aptamers’clinical translation.To...Serving as targeting ligands,aptamers have shown promise in precision medicine.However,the lack of knowledge of the biosafety and metabolism patterns in the human body largely impeded aptamers’clinical translation.To bridge this gap,here we report the first-in-human pharmacokinetics study of protein tyrosine kinase 7 targeted SGC8 aptamer via in vivo PET tracking of gallium-68(^(68)Ga)radiolabeled aptamers.The specificity and binding affinity of a radiolabeled aptamer,named ^(68)Ga[Ga]-NOTA-SGC8,were maintained as proven in vitro.Further preclinical biosafety and biodistribution evaluation confirmed that aptamers have no biotoxicity,potential mutation risks,or genotoxicity at high dosage(40 mg/kg).Based on this result,a first-in-human clinical trial was approved and carried out to evaluate the circulation and metabolism profiles,as well as biosafety,of the radiolabeled SGC8 aptamer in the human body.Taking advantage of the cutting-edge total-body PET,the aptamers’distribution pattern in the human body was acquired in a dynamic fashion.展开更多
基金supported by Natural Science Foundation of China(Grant NO.81972340,82173140,81871196)Shandong Provincial Natural Science Foundation,China(Grant No.ZR202010300086)Academic promotion program of Shandong First Medical University(Grant NO.2019LJ005)。
文摘Glioblastoma is acknowledged as the most aggressive cerebral tumor in adults.However,the efficacy of current standard therapy is seriously undermined by drug resistance and suppressive immune microenvironment.Ferroptosis is a recently discovered form of iron-dependent cell death that may have excellent prospect as chemosensitizer.The utilization of ferropotosis inducer Erastin could significantly mediate chemotherapy sensitization of Temozolomide and exert anti-tumor effects in glioblastoma.In this study,a combination of hydrogel-liposome nanoplatform encapsulatedwith Temozolomide and ferroptosis inducer Erastin was constructed.Theαvβ3 integrin-binding peptide cyclic RGD was utilized to modify codelivery system to achieve glioblastoma targeting strategy.As biocompatible drug reservoirs,cross-linked GelMA(gelatin methacrylamide)hydrogel and cRGD-coated liposome realized the sustained release of internal contents.In the modified intracranial tumor resection model,GelMA-liposome system achieved slow release of Temozolomide and Erastin in situ for more than 14 d.The results indicated that nanoplatform(T+E@LPs-cRGD+GelMA)improved glioblastoma sensitivity to chemotherapeutic temozolomide and exerted satisfactory anti-tumor effects.It was demonstrated that the induction of ferroptosis could be utilized as a therapeutic strategy to overcome drug resistance.Furthermore,transcriptome sequencing was conducted to reveal the underlying mechanism that the nanoplatform(T+E@LPs-cRGD+GelMA)implicated in.It is suggested that GelMA-liposome system participated in the immune response and immunomodulation of glioblastoma via interferon/PD-L1 pathway.Collectively,this study proposed a potential combinatory therapeutic strategy for glioblastoma treatment.
基金Supported by Research Foundation-Flanders(FWO)the KU Leuven Molecular Small Animal Imaging Center Mo SAIC,No.KUL EF/05/08+4 种基金the center of excellence in vivo molecular imaging research(IMIR)KU Leuven projects,No.IOFHB/08/009 and No.IOF-HB/12/018the European Union,AsiaLink Cf P 2006-Europe Aid/123738/C/ACT/Multi-Proposal,No128-498/111National Natural Science Foundation of China,No.81071828Jiangsu Province Natural Science Foundation,No.BK2010594
文摘AIM: To explore the feasibility of using hypericin as an optical imaging probe with affinity for cholesterol for differential fluorescent detection of human gallstones.METHODS: Cholesterol, mixed and pigment stones from cholecystectomy patients were incubated with hypericin or solvent. After 72 h, the stones were analysed for fluorescence(365 nm) and treated with 2-propanol/dimethyl sulfoxide for high performance liquid chromatography(HPLC) analysis. Rats with virtual gallbladder containing human cholesterol, mixed or pigment gallstones(VGHG) received 5 mg/kg hypericin or solvent and VGHG rats with cholesterol stones were given different hypericin doses(5-15 mg/kg). Twelve hours later, the stones were analysed at 365 nm. Biliary excretion and metabolites of hypericin were assessed in common bile duct(CBD) cannulated rats for 9 h using fluorospectrometry, HPLC and matrixassisted laser desorption/ionization-time-of-flight mass spectrometry(MALDI-TOF MS).RESULTS: Homogeneous high fluorescence was seen on cholesterol stones either pre-incubated with hypericin or extracted from VGHG rats receiving hypericin. Mixed stones showed a dotted fluorescent pattern, whereas pigment and solvent-treated ones lacked fluorescence. HPLC showed 7.68, 6.65 and 0.08 × 10^(-3) M of cholesterol in extracts from cholesterol, mixed, and pigment gallstones, respectively. Hypericin accounted for 2.0, 0.5 and 0.2 × 10-6 M in that order. On cholesterol stones from VGHG rats receiving different hypericin doses, a positive correlation was observed between dose and fluorescence. In the bile from CBD-cannulated rats, fluorescence represented 20% of the injected dose with two peaks in 9 h. HPLC analysis revealed that hypericin conjugates reached 60% of the peak area. By MALDI-TOF MS, hypericinglucuronide was detected. CONCLUSION: This study proves the potential use of hypericin for differential fluorescent detection of human gallstones regarding their chemical composition.
基金Supported by the National Natural Science Foundation of China under Grant No.19874078.
文摘Radular teeth of chitons were studied by using magnetic torque-meter and transmission electron microscopy (TEM). The magnetic torque curves give clear evidence of presence of strong uni-axial magnetic anisotropy. The easy axis is along the length direction of tongue-like radula. The TEM pattern shows that long chip-like magnetite nano-scaled particles packed in the radular teeth with both uni-axial shape anisotropy and magneto-crystalline anisotropy.
文摘Premature ovarian failure refers to a disease in which women usually present with amenorrhea,infertility,decreased estrogen secretion,and increased gonadotropin before the age of 40.It seriously endangers women’s health,making them prone to various endocrine reproductive and even systemic disorders.Its pathogenesis remains unclear;however,it may be related to genetic,immune,enzyme deficiency,iatrogenic,cyclin,psychology,and other factors.Traditional Chinese medicine believes that its etiology is related to the kidney,liver,and spleen.It can be divided into kidney deficiency and liver depression syndrome,liver and kidney Yin deficiency syndrome,spleen and kidney Yang deficiency syndrome,and so on.Traditional Chinese medicine is mainly made up of oral Chinese medicine,acupuncture,and other therapies.Through literature research,this paper discusses the etiology,pathological mechanism,and treatment of premature ovarian failure in the field of traditional Chinese medicine.
文摘目的探讨碳酸钙联合维生素K对糖皮质激素性骨质疏松症(glucocorticoids-induced osteoporosis,GIOP)患儿骨代谢指标、Th1细胞因子及安全性的影响。方法本研究纳入96例GIOP患儿进行研究,按随机数字表法分为对照组与观察组,每组各48例。对照组使用碳酸钙治疗,观察组使用碳酸钙联合维生素K治疗。对比分析两组患儿治疗前后骨代谢指标血清I型胶原氨基前端肽(type I procollagen amino-terminal peptide,PINP)、血清β-胶原特殊序列(βcollagen special sequence,β-CTX)、骨钙素(osteocalcin,BGP)、血清骨碱性磷酸酶(bone alkaline phosphatase,BALP)、Th1细胞因子γ干扰素(interferon-γ,IFN-γ)降低,白细胞介素2(interleukin-2,IL-2)水平及不良反应情况。结果两组患者一般资料比较差异无统计学意义(均P>0.05)。与治疗前比较,两组治疗后股骨颈骨密度均增强,且观察组(-1.02±0.49)较对照组(-1.52±0.65)改善更明显(t=4.26,P<0.001)。与治疗前比较,两组治疗后PINP、β-CTX、BGP和BALP等水平降低,且相对于对照组(PINP:31.65±6.58;β-CTX:0.34±0.05;BGP:4.95±1.28;BALP:40.54±7.84),观察组治疗后各指标(PINP:26.54±7.06;β-CTX:0.24±0.03;BGP:3.05±1.09;BALP:35.96±7.02)改善更显著(t=3.67,P<0.001;t=11.88,P<0.001;t=7.83,P<0.001;t=3.02,P<0.003)。与治疗前比较,两组治疗后IL-2水平提高但IFN-γ水平降低,且相对于对照组(IL-2:163.89±30.85;IFN-γ:196.61±21.05),观察组治疗后IL-2水平(198.32±32.14)更高且IFN-γ水平(163.25±18.43)更低(t=5.35,P<0.001;t=8.26,P<0.001)。两组不良反应发生率比较差异无统计学意义(χ^(2)=0.15,P=0.695)。结论碳酸钙联合维生素K治疗GIOP患儿,可改善患儿骨代谢指标、Th1细胞因子水平,临床治疗效果良好。
基金the National Key Research and Development Program of China(No.2020YFA0909000 and 2020YFA0210800)the National Science Foundation of China(No.22204102,52161160307,91953000,and 2182781)+2 种基金Shanghai Sailing Program,Shanghai Committee of Science and Technology,China(No.21YF1425700)Excellent Academic Leader Programme of Shanghai Health Commission(2022XD033)Core Facility of Basic Medical Sciences in Shanghai Jiao Tong University School of Medicine,and the Innovative Research Team of High-Level Local Universities in Shanghai,China.
文摘Serving as targeting ligands,aptamers have shown promise in precision medicine.However,the lack of knowledge of the biosafety and metabolism patterns in the human body largely impeded aptamers’clinical translation.To bridge this gap,here we report the first-in-human pharmacokinetics study of protein tyrosine kinase 7 targeted SGC8 aptamer via in vivo PET tracking of gallium-68(^(68)Ga)radiolabeled aptamers.The specificity and binding affinity of a radiolabeled aptamer,named ^(68)Ga[Ga]-NOTA-SGC8,were maintained as proven in vitro.Further preclinical biosafety and biodistribution evaluation confirmed that aptamers have no biotoxicity,potential mutation risks,or genotoxicity at high dosage(40 mg/kg).Based on this result,a first-in-human clinical trial was approved and carried out to evaluate the circulation and metabolism profiles,as well as biosafety,of the radiolabeled SGC8 aptamer in the human body.Taking advantage of the cutting-edge total-body PET,the aptamers’distribution pattern in the human body was acquired in a dynamic fashion.
