P-113 is a fragment of natural occurring peptide Histatin 5 found in human saliva. This peptide exhibited broad spectrum of antibacterial and antifungal biological activities. In this study, bifunctional P-113 peptide...P-113 is a fragment of natural occurring peptide Histatin 5 found in human saliva. This peptide exhibited broad spectrum of antibacterial and antifungal biological activities. In this study, bifunctional P-113 peptides 2–5 were designed as Sortase A substrates and synthesized by solid support peptide synthesis,where the N-terminus were equipped with glycine and its analogues, and C-terminus were extended with LPETGGS, respectively. Under Sortase A catalyzed condition, head to tail cyclization products 7–10were afforded in yields from 76% to 93%. The conformation insights of linear peptides 2–5 and cyclic analogues 7–10 in aqueous buffers and in trifluroethanol（TFE） analyzed by circular dichroism（CD）suggested that a-helix structures were produced progressively in hydrophobic environment independent of the cyclization, which displayed the similar behavior as parent peptide P-113.展开更多
Gliomas are the most common intracranial tumors with poor survival and high mortality.Furthermore,the clinical efficacy of current drugs is still not ideal;despite the development of several therapeutic drugs over the...Gliomas are the most common intracranial tumors with poor survival and high mortality.Furthermore,the clinical efficacy of current drugs is still not ideal;despite the development of several therapeutic drugs over the past decades and tumor progression or recurrence is inevitable in many patients.RNAibased therapy presents a novel disease-related gene targeting therapy,including otherwise undruggable genes,and generates therapeutic options.However,the therapeutic effect of siRNA is hindered by multiple biological barriers,primarily the blood-brain barrier(BBB).A glycoprotein-derived peptide-mediated delivery system is the preferred option to resolve this phenomenon.RDP,a polypeptide composed of 15 amino acids derived from rabies virus glycoprotein(RVG),possesses an N-type acetylcholine receptor(nAChR)-binding efficiency similar to that of RVG29.Given its lower cost and small particle size when used as a ligand,RDP should be extensively evaluated.First,we verified the brain-targeting efficacyy of RDP at the cellular and animal levels and further explored the possibility of using the RDP-oligoarginine peptide(designated RDP-5R)as a bio-safe vehicle to deliver therapeutic siRNA into glioma cells in vitro and in vivo.The polypeptide carrier possesses a diblock design composed of oligoarginine for binding siRNA through electrostatic interactions and RDP for cascade BBB-and glioma cell-targeting.The results indicated that RDP-R5/siRNA nanoparticles exhibited stable and suitable physicochemical properties for in vivo application,desirable glioma-targeting effects,and therapeutic efficiency.As a novel and efficient polypeptide carrier,RDP-based polypeptides hold great promise as a noninvasive,safe,and efficient treatment for various brain diseases.展开更多
As one of the most important and influential peptide conferences in the world,Chinese International Peptide Symposium(CPS)was founded in 1990 and has been held every two years for14 consecutive sessions.From July 4tht...As one of the most important and influential peptide conferences in the world,Chinese International Peptide Symposium(CPS)was founded in 1990 and has been held every two years for14 consecutive sessions.From July 4thto 6th,2018,the 15th CPS will be held in Shenzhen and hosted by Tsinghua University.This conference will focus on the topics of"Peptide:Technological Innovation and a Better Life",covering the synthesis,structure and function of peptides and proteins,peptide-based drug discovery,展开更多
Objective Loss-of-function mutation of p53,a tumor suppressor gene,is an important mechanism for the development of human cancers. In this study we tried to transfect p53N15-based fusion peptide into H1299,a lung canc...Objective Loss-of-function mutation of p53,a tumor suppressor gene,is an important mechanism for the development of human cancers. In this study we tried to transfect p53N15-based fusion peptide into H1299,a lung cancer cell line,and evaluate the anti-tumor effects of the fusion peptide. Methods Adeno-associated virus (AAV) vectors were used for transfecting p53N15 fusion peptide into p53-null lung adenocarcinoma H1299 cells.展开更多
目的研究多肽P-15对小牛骨表面生长的大鼠成骨细胞附着、增殖、分化的影响。方法对照组和实验组分别采用单纯无机小牛骨粉(anorganic bone mineral,ABM)和复合P-15的无机小牛骨粉接种大鼠成骨细胞进行体外培养。四甲基偶氮唑蓝[3-(4,5-d...目的研究多肽P-15对小牛骨表面生长的大鼠成骨细胞附着、增殖、分化的影响。方法对照组和实验组分别采用单纯无机小牛骨粉(anorganic bone mineral,ABM)和复合P-15的无机小牛骨粉接种大鼠成骨细胞进行体外培养。四甲基偶氮唑蓝[3-(4,5-dimehyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazoliumbromide,MTT]比色法检测大鼠成骨细胞在2组骨粉表面附着、增殖的速度,倒置相差显微镜观察成骨细胞在2组骨粉表面及周围的增殖情况,用对硝基苯磷酸二钠盐(p-nitrophenyl phosphate,PNPP)法检测2组成骨细胞碱性磷酸酶(alkaline phosphatase,ALP)活性。结果成骨细胞体外培养24h,实验组与对照组MTT比色法检测的光密度值分别为1.597±0.035、1.239±0.063,差异有统计学意义(P<0.01)。培养72h,实验组和对照组PNPP法检测的ALP活性分别为(35.533±1.051)金氏单位/100mL和(34.645±1.187)金氏单位/100mL,实验组略高于对照组,但差异无统计学意义(P>0.05)。结论多肽P-15加快了大鼠成骨细胞在骨粉表面粘附、增殖的速度,但对大鼠成骨细胞的分化无明显促进作用。展开更多
从Nrf2信号通路探讨淫羊藿苷(icariin,ICA)对D-半乳糖(D-galactose,D-Gal)诱导的小鼠睾丸支持细胞株15P-1细胞损伤的保护作用。将15P-1细胞分为对照组(control)、150 mM D-Gal处理组、D-Gal+ICA(0.5μM)组和D-Gal+ICA(1.0μM)组。RT-PC...从Nrf2信号通路探讨淫羊藿苷(icariin,ICA)对D-半乳糖(D-galactose,D-Gal)诱导的小鼠睾丸支持细胞株15P-1细胞损伤的保护作用。将15P-1细胞分为对照组(control)、150 mM D-Gal处理组、D-Gal+ICA(0.5μM)组和D-Gal+ICA(1.0μM)组。RT-PCR法和Western blot法检测15P-1细胞分泌的相关因子GDNF、BMP4和SCF mRNA和蛋白的表达水平。Western blot法检测15P-1细胞紧密连接相关蛋白Occludin和Claudin-1、Nrf2信号通路相关蛋白Nrf2、HO-1和NQO-1的蛋白表达水平。免疫荧光法检测Nrf2表达及定位。与对照组相比,D-Gal处理组15P-1细胞分泌的相关因子GDNF、BMP4和SCF的mRNA和蛋白表达水平均显著下降,而给予ICA后均显著升高。此外,与对照组相比,D-Gal处理组15P-1细胞Occludin、Claudin-1、Nrf2、HO-1和NQO-1的蛋白表达水平均显著下降,而ICA可显著上调上述相关蛋白的表达。免疫荧光结果进一步显示,ICA可上调15P-1细胞核内Nrf2蛋白表达。ICA可减轻D-Gal诱导的15P-1细胞损伤,并改善其功能,其机制可能与上调Nrf2信号通路相关蛋白有关。展开更多
Introduction: Lumbar fusion as low back pain treatment continues to be a challenge because of the multiple techniques and materials available, most popular techniques include Transforaminal lumbar interbody fusion (TL...Introduction: Lumbar fusion as low back pain treatment continues to be a challenge because of the multiple techniques and materials available, most popular techniques include Transforaminal lumbar interbody fusion (TLIF), Lateral lumbar interbody fusion (LLIF) and Anterior lumbar interbody fusion (ALIF). Successful lumbar fusion is associated with better clinical outcomes, and it is enhanced and targeted through the use of bone graft materials as an osteogenic cell binding peptide P-15, bound to an anorganic bone mineral (ABM). This peptide improves bone formation when used in fixation devices in a targeted and limited way to the implant surface by activating osteoblast precursor cells;by the osteogenic, osteoinductive and osteoconductive stimuli. The main objective of this study is to standardize the lumbar fusion process in the 3 techniques and achieve a more efficient and predictable lumbar fusion, evaluating results with radiological and clinical scales. Material and Methods: Patients underwent lumbar fusion with the use of P-15 Osteogenic Cell Binding Peptide, bound to an anorganic bone mineral (P-15/ABM) bone graft (5 cc) in three different techniques (TLIF, LLIF, ALIF), achieving a total of 100 lumbar levels. Radiological outcomes included fusion rates per Hounsfield Units at computed tomography (CT) scan and Lenke scale. Clinical outcomes were evaluated via the Oswestry Disability Index (ODI), Short Form Performance (SPF-36) and Visual Analog Scale (VAS and VASs) for pain and satisfaction. Results: 67 patients completed the 12 months follow-up, showing no differences in fusion rates between techniques. (Computed Tomography Hounsfield Units) CTHU reaches more than 200 UH at 3 months follow-up and continues fusion process till 12-month follow-up. Clinical scales showed no disability at ODI, improvement at VAS and VASs scales, absence of health restrictions at SPF-36 score since 6 months follow up. Conclusion: Bone graft volume of 5 cc is adequate for achieving successful lumbar fusion, regardless of the surgical technique employed.展开更多
基金supported by the National Natural Science Foundation of China(No.21472070)the Project for Jiangsu Scientific and Technological Innovation Team+2 种基金Fund for Jiangsu Distinguished Professorship ProgramProject Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions,the 111 Project(No.111-2-06)the Jiangsu province“Collaborative Innovation Center for Advanced Industrial Fermentation”industry development program
文摘P-113 is a fragment of natural occurring peptide Histatin 5 found in human saliva. This peptide exhibited broad spectrum of antibacterial and antifungal biological activities. In this study, bifunctional P-113 peptides 2–5 were designed as Sortase A substrates and synthesized by solid support peptide synthesis,where the N-terminus were equipped with glycine and its analogues, and C-terminus were extended with LPETGGS, respectively. Under Sortase A catalyzed condition, head to tail cyclization products 7–10were afforded in yields from 76% to 93%. The conformation insights of linear peptides 2–5 and cyclic analogues 7–10 in aqueous buffers and in trifluroethanol（TFE） analyzed by circular dichroism（CD）suggested that a-helix structures were produced progressively in hydrophobic environment independent of the cyclization, which displayed the similar behavior as parent peptide P-113.
基金supported by CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-026,China).
文摘Gliomas are the most common intracranial tumors with poor survival and high mortality.Furthermore,the clinical efficacy of current drugs is still not ideal;despite the development of several therapeutic drugs over the past decades and tumor progression or recurrence is inevitable in many patients.RNAibased therapy presents a novel disease-related gene targeting therapy,including otherwise undruggable genes,and generates therapeutic options.However,the therapeutic effect of siRNA is hindered by multiple biological barriers,primarily the blood-brain barrier(BBB).A glycoprotein-derived peptide-mediated delivery system is the preferred option to resolve this phenomenon.RDP,a polypeptide composed of 15 amino acids derived from rabies virus glycoprotein(RVG),possesses an N-type acetylcholine receptor(nAChR)-binding efficiency similar to that of RVG29.Given its lower cost and small particle size when used as a ligand,RDP should be extensively evaluated.First,we verified the brain-targeting efficacyy of RDP at the cellular and animal levels and further explored the possibility of using the RDP-oligoarginine peptide(designated RDP-5R)as a bio-safe vehicle to deliver therapeutic siRNA into glioma cells in vitro and in vivo.The polypeptide carrier possesses a diblock design composed of oligoarginine for binding siRNA through electrostatic interactions and RDP for cascade BBB-and glioma cell-targeting.The results indicated that RDP-R5/siRNA nanoparticles exhibited stable and suitable physicochemical properties for in vivo application,desirable glioma-targeting effects,and therapeutic efficiency.As a novel and efficient polypeptide carrier,RDP-based polypeptides hold great promise as a noninvasive,safe,and efficient treatment for various brain diseases.
文摘As one of the most important and influential peptide conferences in the world,Chinese International Peptide Symposium(CPS)was founded in 1990 and has been held every two years for14 consecutive sessions.From July 4thto 6th,2018,the 15th CPS will be held in Shenzhen and hosted by Tsinghua University.This conference will focus on the topics of"Peptide:Technological Innovation and a Better Life",covering the synthesis,structure and function of peptides and proteins,peptide-based drug discovery,
文摘Objective Loss-of-function mutation of p53,a tumor suppressor gene,is an important mechanism for the development of human cancers. In this study we tried to transfect p53N15-based fusion peptide into H1299,a lung cancer cell line,and evaluate the anti-tumor effects of the fusion peptide. Methods Adeno-associated virus (AAV) vectors were used for transfecting p53N15 fusion peptide into p53-null lung adenocarcinoma H1299 cells.
文摘目的研究多肽P-15对小牛骨表面生长的大鼠成骨细胞附着、增殖、分化的影响。方法对照组和实验组分别采用单纯无机小牛骨粉(anorganic bone mineral,ABM)和复合P-15的无机小牛骨粉接种大鼠成骨细胞进行体外培养。四甲基偶氮唑蓝[3-(4,5-dimehyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazoliumbromide,MTT]比色法检测大鼠成骨细胞在2组骨粉表面附着、增殖的速度,倒置相差显微镜观察成骨细胞在2组骨粉表面及周围的增殖情况,用对硝基苯磷酸二钠盐(p-nitrophenyl phosphate,PNPP)法检测2组成骨细胞碱性磷酸酶(alkaline phosphatase,ALP)活性。结果成骨细胞体外培养24h,实验组与对照组MTT比色法检测的光密度值分别为1.597±0.035、1.239±0.063,差异有统计学意义(P<0.01)。培养72h,实验组和对照组PNPP法检测的ALP活性分别为(35.533±1.051)金氏单位/100mL和(34.645±1.187)金氏单位/100mL,实验组略高于对照组,但差异无统计学意义(P>0.05)。结论多肽P-15加快了大鼠成骨细胞在骨粉表面粘附、增殖的速度,但对大鼠成骨细胞的分化无明显促进作用。
文摘Introduction: Lumbar fusion as low back pain treatment continues to be a challenge because of the multiple techniques and materials available, most popular techniques include Transforaminal lumbar interbody fusion (TLIF), Lateral lumbar interbody fusion (LLIF) and Anterior lumbar interbody fusion (ALIF). Successful lumbar fusion is associated with better clinical outcomes, and it is enhanced and targeted through the use of bone graft materials as an osteogenic cell binding peptide P-15, bound to an anorganic bone mineral (ABM). This peptide improves bone formation when used in fixation devices in a targeted and limited way to the implant surface by activating osteoblast precursor cells;by the osteogenic, osteoinductive and osteoconductive stimuli. The main objective of this study is to standardize the lumbar fusion process in the 3 techniques and achieve a more efficient and predictable lumbar fusion, evaluating results with radiological and clinical scales. Material and Methods: Patients underwent lumbar fusion with the use of P-15 Osteogenic Cell Binding Peptide, bound to an anorganic bone mineral (P-15/ABM) bone graft (5 cc) in three different techniques (TLIF, LLIF, ALIF), achieving a total of 100 lumbar levels. Radiological outcomes included fusion rates per Hounsfield Units at computed tomography (CT) scan and Lenke scale. Clinical outcomes were evaluated via the Oswestry Disability Index (ODI), Short Form Performance (SPF-36) and Visual Analog Scale (VAS and VASs) for pain and satisfaction. Results: 67 patients completed the 12 months follow-up, showing no differences in fusion rates between techniques. (Computed Tomography Hounsfield Units) CTHU reaches more than 200 UH at 3 months follow-up and continues fusion process till 12-month follow-up. Clinical scales showed no disability at ODI, improvement at VAS and VASs scales, absence of health restrictions at SPF-36 score since 6 months follow up. Conclusion: Bone graft volume of 5 cc is adequate for achieving successful lumbar fusion, regardless of the surgical technique employed.
