Recently,a work jointly studied by Ling Li and coworkers1 was published in Nature Materials,describing a reconfigurable DNA origami nanodevice designed to regulate CD95 death-inducing signaling of immune cells.The res...Recently,a work jointly studied by Ling Li and coworkers1 was published in Nature Materials,describing a reconfigurable DNA origami nanodevice designed to regulate CD95 death-inducing signaling of immune cells.The researchers utilized the DNA origami nanodevice to establish selective local immune tolerance and demonstrated its ability to alleviate rheumatoid arthritis(RA)in the inflamed synovial tissue of mice without causing any obvious side effects(Fig.1).This approach presents a novel idea for the development of drug interventions involving ligandreceptor interactions.展开更多
BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL system...BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical practice.In this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic’s 670G HCL in real-world clinical practice.AIM To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D.METHODS We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1C:7.6%±0.8%)who were treated with HCL at Joslin Clinic from 2017 to 2019.We measured A1C and percent of glucose time-in-range(%TIR)at baseline and 12 months.We measured percent time in auto mode(%TiAM)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management.RESULTS At 12 mo,A1C decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAM was only 64.3%±32.8%and was not associated with A1C,%TIR or PROs.PROs,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(P<0.001).Hypoglycemia fear survey/worry scale decreased significantly by 24.9%(P<0.000);Problem Areas In Diabetes reduced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes.WHO-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HCL system.Finally,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration of sleep from baseline to 12 mo.CONCLUSION The use of HCL in real-world clinical practice for one year was associated with significant improvements in A1C,%TIR,physical functioning,hypoglycemia fear,emotional distress,and emotional burden related to diabetes management.However,these changes were not associated with time in auto mode.展开更多
Bladder cancer is one of the concerning malignancies worldwide,which is lacking effective targeted therapy.Gene therapy is a potential approach for bladder cancer treatment.While,a safe and effective targeted gene del...Bladder cancer is one of the concerning malignancies worldwide,which is lacking effective targeted therapy.Gene therapy is a potential approach for bladder cancer treatment.While,a safe and effective targeted gene delivery system is urgently needed for prompting the bladder cancer treatment in vivo.In this study,we confirmed that the bladder cancer had CD44 overexpression and small interfering RNAs(siRNA)with high interfere to Bcl2 oncogene were designed and screened.Then hyaluronic acid dialdehyde(HAD)was prepared in an ethanol-water mixture and covalently conjugated to the chitosan nanoparticles(CS-HAD NPs)to achieve CD44 targeted siRNA delivery.The in vitro and in vivo evaluations indicated that the siRNA-loaded CS-HAD NPs(siRNA@CS-HAD NPs)were approximately 100 nm in size,with improved stability,high siRNA encapsulation efficiency and low cytotoxicity.CS-HAD NPs could target to CD44 receptor and deliver the therapeutic siRNA into T24 bladder cancer cells through a ligand-receptor-mediated targeting mechanism and had a specific accumulation capacity in vivo to interfere the targeted oncogene Bcl2 in bladder cancer.Overall,a CD44 targeted gene delivery system based on natural macromolecules was developed for effective bladder cancer treatment,which could be more conducive to clinical application due to its simple preparation and high biological safety.展开更多
The breast cancer is one of the most common cancer affecting millions of lives worldwide.Though the prevalence of breast cancer is worldwide;however,the developing nations are having a comparatively higher percentage ...The breast cancer is one of the most common cancer affecting millions of lives worldwide.Though the prevalence of breast cancer is worldwide;however,the developing nations are having a comparatively higher percentage of breast cancer cases and associated complications.The molecular etiology behind breast cancer is complex and involves several regulatory molecules and their downstream signaling.Studies have demonstrated that the CD44 remains one of the major molecule associated not only in breast cancer but also several other kinds of tumors.The complex structure and functioning of CD44 posed a challenge to develop and deliver precise anti-cancerous drugs against targeted tissue.There are more than 20 isoforms of CD44 reported till date associated with several kinds of tumor in the using breast cancer.The success of any anti-cancerous therapy largely depends on the precise drug delivery system,and in modern days nanotechnology-based drug delivery vehicles are the first choice not only for cancer but several other chronic diseases as well.The Carbon nanotubes(CNTs)have shown tremendous scope in delivering the drug by targeting a particular receptor and molecules.Functionalized CNTs including both SWCNTs and MWCNTs are a pioneer in drug delivery with higher efficacy.The present work emphasized mainly on the potential of CNTs including both SWCNTs and MWCNTs in drug delivery for anti-cancerous therapy.The review provides a comprehensive overview of the development of various CNTs and their validation for effective drug delivery.The work focus on drug delivery approaches for breast cancer,precisely targeting CD44 molecule.展开更多
基金support from the National Natural Science Foundation of China(82072087,31970893,32270976)funding by Science and Technology Projects in Guangzhou(202206010087,China).
文摘Recently,a work jointly studied by Ling Li and coworkers1 was published in Nature Materials,describing a reconfigurable DNA origami nanodevice designed to regulate CD95 death-inducing signaling of immune cells.The researchers utilized the DNA origami nanodevice to establish selective local immune tolerance and demonstrated its ability to alleviate rheumatoid arthritis(RA)in the inflamed synovial tissue of mice without causing any obvious side effects(Fig.1).This approach presents a novel idea for the development of drug interventions involving ligandreceptor interactions.
文摘BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical practice.In this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic’s 670G HCL in real-world clinical practice.AIM To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D.METHODS We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1C:7.6%±0.8%)who were treated with HCL at Joslin Clinic from 2017 to 2019.We measured A1C and percent of glucose time-in-range(%TIR)at baseline and 12 months.We measured percent time in auto mode(%TiAM)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management.RESULTS At 12 mo,A1C decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAM was only 64.3%±32.8%and was not associated with A1C,%TIR or PROs.PROs,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(P<0.001).Hypoglycemia fear survey/worry scale decreased significantly by 24.9%(P<0.000);Problem Areas In Diabetes reduced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes.WHO-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HCL system.Finally,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration of sleep from baseline to 12 mo.CONCLUSION The use of HCL in real-world clinical practice for one year was associated with significant improvements in A1C,%TIR,physical functioning,hypoglycemia fear,emotional distress,and emotional burden related to diabetes management.However,these changes were not associated with time in auto mode.
基金This study was financially supported by the National Natural Science Foundation of China(81772713,81472411,81401899,81372752)Taishan Scholar Program of Shandong Province(tsqn20161077)+4 种基金Key Research and Development Program of Shandong Province(2018GSF118197)China Postdoctoral Science Foundation(2017M622144)Qingdao Postdoctoral Application Research Project.Prof.Zhang acknowledged the support from Academy of Finland(Grant no.328933)Sigrid Juselius Foundation(Grant no.28002247K1)We thank Dr.Chang Liu fromÅbo Akademi University for giving some advice to analyze the TGA data,and Ms.Qian Wen from Biomedical Center of Qingdao University for her guidance and support of in vivo fluorescence imaging.
文摘Bladder cancer is one of the concerning malignancies worldwide,which is lacking effective targeted therapy.Gene therapy is a potential approach for bladder cancer treatment.While,a safe and effective targeted gene delivery system is urgently needed for prompting the bladder cancer treatment in vivo.In this study,we confirmed that the bladder cancer had CD44 overexpression and small interfering RNAs(siRNA)with high interfere to Bcl2 oncogene were designed and screened.Then hyaluronic acid dialdehyde(HAD)was prepared in an ethanol-water mixture and covalently conjugated to the chitosan nanoparticles(CS-HAD NPs)to achieve CD44 targeted siRNA delivery.The in vitro and in vivo evaluations indicated that the siRNA-loaded CS-HAD NPs(siRNA@CS-HAD NPs)were approximately 100 nm in size,with improved stability,high siRNA encapsulation efficiency and low cytotoxicity.CS-HAD NPs could target to CD44 receptor and deliver the therapeutic siRNA into T24 bladder cancer cells through a ligand-receptor-mediated targeting mechanism and had a specific accumulation capacity in vivo to interfere the targeted oncogene Bcl2 in bladder cancer.Overall,a CD44 targeted gene delivery system based on natural macromolecules was developed for effective bladder cancer treatment,which could be more conducive to clinical application due to its simple preparation and high biological safety.
基金The author would like to acknowledge the Department of Science and Technology(DST),Government of India for financial support(Sanction No SR/WOS-A/LS-314/2016).The author also acknowledges Rajiv Gandhi Proudyogiki Vishwavidyalaya,Bhopal,India,for providing a facility for the current study.
文摘The breast cancer is one of the most common cancer affecting millions of lives worldwide.Though the prevalence of breast cancer is worldwide;however,the developing nations are having a comparatively higher percentage of breast cancer cases and associated complications.The molecular etiology behind breast cancer is complex and involves several regulatory molecules and their downstream signaling.Studies have demonstrated that the CD44 remains one of the major molecule associated not only in breast cancer but also several other kinds of tumors.The complex structure and functioning of CD44 posed a challenge to develop and deliver precise anti-cancerous drugs against targeted tissue.There are more than 20 isoforms of CD44 reported till date associated with several kinds of tumor in the using breast cancer.The success of any anti-cancerous therapy largely depends on the precise drug delivery system,and in modern days nanotechnology-based drug delivery vehicles are the first choice not only for cancer but several other chronic diseases as well.The Carbon nanotubes(CNTs)have shown tremendous scope in delivering the drug by targeting a particular receptor and molecules.Functionalized CNTs including both SWCNTs and MWCNTs are a pioneer in drug delivery with higher efficacy.The present work emphasized mainly on the potential of CNTs including both SWCNTs and MWCNTs in drug delivery for anti-cancerous therapy.The review provides a comprehensive overview of the development of various CNTs and their validation for effective drug delivery.The work focus on drug delivery approaches for breast cancer,precisely targeting CD44 molecule.
