Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofissionassociated cell death(...Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofissionassociated cell death(MFAD)by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy.By screening a series of paninhibitors,we identified pracinostat,a pan-histone deacetylase(HDAC)inhibitor,as a novel MFAD inducer,that exhibited a significant anticancer effect on colorectal cancer(CRC)in vivo and in vitro.Pracinostat increased the expression of cyclin-dependent kinase 5(CDK5)and induced its acetylation at residue lysine 33,accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynaminrelated protein 1(Drp1)-mediated mitochondrial peripheral fission.CRC cells with high level of CDK5(CDK5-high)displayed midzone mitochondrial division that was associated with oncogenic phenotype,but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells.Mechanistically,pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor(MFF)to mitochondrial fission 1 protein(FIS1).Thus,our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells,which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.展开更多
Acupuncture,with its unique set of theories and its evident results in clinical practice is an important part of traditional Chinese medicine(TCM),and gaining recognition worldwide for the past few years.Although acup...Acupuncture,with its unique set of theories and its evident results in clinical practice is an important part of traditional Chinese medicine(TCM),and gaining recognition worldwide for the past few years.Although acupuncture treatment is generally accepted by the public,a few western researchers believe that sufficient evidence of its efficiency is still currently lacking,therefore creating a challenge of its acceptance on a wider scale.This article suggests the concepts of acupuncture behind clinical researches by reviewing the clinical researches done,analyzing the existing problems,and integrating real life acupuncture into the research process.By increasing the credibility of acupuncture,its reach can be extended globally and to more countries and regions.展开更多
The magnetic Fe_(3)O_(4)@C@TiO_(2)microspheres with multilevel yolk-shell structure were successfully prepared by combining sol-gel and simple hydrothermal methods.The features of the as-obtained Fe_(3)O_(4)@C@TiO_(2)...The magnetic Fe_(3)O_(4)@C@TiO_(2)microspheres with multilevel yolk-shell structure were successfully prepared by combining sol-gel and simple hydrothermal methods.The features of the as-obtained Fe_(3)O_(4)@C@TiO_(2)microspheres were investigated by Fourier transform infrared(FTIR)spectra,scanning electron microscopy(SEM),powder X-ray diffraction(XRD),N_(2)adsorptiondesorption measurements and transmission electron microscopy(TEM).Fe_(3)O_(4)@C@TiO_(2)was used as an adsorbent to explore its adsorption properties of oxytetracycline hydrochloride(OTC-HCl)by changing initial concentration and time.The results suggest that the maximum adsorption of Fe_(3)O_(4)@C@TiO_(2)is 87.3 mg·g^(-1),and the time reaching the absorption equilibrium is 60 min.Langmuir model fits to data better than the Freundlich model,and the kinetic properties are well described by the pseudo-second-order model.In addition,the synthesized composites’reusability without obvious deterioration in performance is demonstrated by three cycles.展开更多
Pain and inflammatory diseases are important clinical indications of acupuncture,which have been widely accepted in the international community.Previous studies have been focusing on rapid analgesia of acupuncture thr...Pain and inflammatory diseases are important clinical indications of acupuncture,which have been widely accepted in the international community.Previous studies have been focusing on rapid analgesia of acupuncture through the regulation of nervous system,but few studies on the inflammation regulatory mechanisms in which acupuncture inhibits the peripheral sensitization-induced pain.Based on studies concerning acupoint mechanisms of acupuncture actions and related researches on acupuncture regulating neuroendocrine and immune systems,we put forward the scientific hypothesis that acupuncture regulates neuroendocrine-immune(NEI)network and key response media therein,so as to achieve anti-inflammatory and analgesic effects in target organs.We have established a platform for acupuncture at ST36 to alleviate inflammatory pain in adjuvant induced arthritic rats.Based on the complex network analysis of multi-dimensional data from multi-time point and multi-site detection of NEI common signaling molecules,we have clarified the regulatory effects of acupuncture on NEI network and corresponding downstream immune network.Results indicated that monocytes/macrophages are the key targeting cells of acupuncture regulation,and acupuncture may display the anti-inflammatory and analgesic effects by regulating polarization of T cells in lymph nodes and polarization of M1/M2 macrophages in inflamed joints/paws.In addition,we have spotted a key molecule for acupuncture analgesia,CXCL1,as well as clarified the novel central analgesic mechanism of acupuncture mediated by CXCL1/CXCR2 desensitization.Thereby,we have provided novel evidence of the anti-inflammatory and analgesic actions of acupuncture through regulating NEI network and several key substances,highlighting a systemic research paradigm for investigating mechanisms of acupuncture actions.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:82103208,and 82002948)the Guangdong Basic and Applied Basic Research Foundation(Grant Nos.:2022A1515220212,and 2023A1515030115)+1 种基金National Key R&D Program of China(Grant No.:2020YFE0202200)Jinan University National College Students'Innovation and Entrepreneurship Training Program(Program No.:202110559085).
文摘Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofissionassociated cell death(MFAD)by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy.By screening a series of paninhibitors,we identified pracinostat,a pan-histone deacetylase(HDAC)inhibitor,as a novel MFAD inducer,that exhibited a significant anticancer effect on colorectal cancer(CRC)in vivo and in vitro.Pracinostat increased the expression of cyclin-dependent kinase 5(CDK5)and induced its acetylation at residue lysine 33,accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynaminrelated protein 1(Drp1)-mediated mitochondrial peripheral fission.CRC cells with high level of CDK5(CDK5-high)displayed midzone mitochondrial division that was associated with oncogenic phenotype,but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells.Mechanistically,pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor(MFF)to mitochondrial fission 1 protein(FIS1).Thus,our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells,which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.
文摘Acupuncture,with its unique set of theories and its evident results in clinical practice is an important part of traditional Chinese medicine(TCM),and gaining recognition worldwide for the past few years.Although acupuncture treatment is generally accepted by the public,a few western researchers believe that sufficient evidence of its efficiency is still currently lacking,therefore creating a challenge of its acceptance on a wider scale.This article suggests the concepts of acupuncture behind clinical researches by reviewing the clinical researches done,analyzing the existing problems,and integrating real life acupuncture into the research process.By increasing the credibility of acupuncture,its reach can be extended globally and to more countries and regions.
基金the Major Science and Technology Program for Water Pollution Control and Treatment(No.2013ZX07202-010)。
文摘The magnetic Fe_(3)O_(4)@C@TiO_(2)microspheres with multilevel yolk-shell structure were successfully prepared by combining sol-gel and simple hydrothermal methods.The features of the as-obtained Fe_(3)O_(4)@C@TiO_(2)microspheres were investigated by Fourier transform infrared(FTIR)spectra,scanning electron microscopy(SEM),powder X-ray diffraction(XRD),N_(2)adsorptiondesorption measurements and transmission electron microscopy(TEM).Fe_(3)O_(4)@C@TiO_(2)was used as an adsorbent to explore its adsorption properties of oxytetracycline hydrochloride(OTC-HCl)by changing initial concentration and time.The results suggest that the maximum adsorption of Fe_(3)O_(4)@C@TiO_(2)is 87.3 mg·g^(-1),and the time reaching the absorption equilibrium is 60 min.Langmuir model fits to data better than the Freundlich model,and the kinetic properties are well described by the pseudo-second-order model.In addition,the synthesized composites’reusability without obvious deterioration in performance is demonstrated by three cycles.
基金supported by the National Natural Science Foundation of China(NSFC)No.81330088,81873369,81873368,81973939,81973944,81804182Natural science foundation of Zhejiang province LY20H270008
文摘Pain and inflammatory diseases are important clinical indications of acupuncture,which have been widely accepted in the international community.Previous studies have been focusing on rapid analgesia of acupuncture through the regulation of nervous system,but few studies on the inflammation regulatory mechanisms in which acupuncture inhibits the peripheral sensitization-induced pain.Based on studies concerning acupoint mechanisms of acupuncture actions and related researches on acupuncture regulating neuroendocrine and immune systems,we put forward the scientific hypothesis that acupuncture regulates neuroendocrine-immune(NEI)network and key response media therein,so as to achieve anti-inflammatory and analgesic effects in target organs.We have established a platform for acupuncture at ST36 to alleviate inflammatory pain in adjuvant induced arthritic rats.Based on the complex network analysis of multi-dimensional data from multi-time point and multi-site detection of NEI common signaling molecules,we have clarified the regulatory effects of acupuncture on NEI network and corresponding downstream immune network.Results indicated that monocytes/macrophages are the key targeting cells of acupuncture regulation,and acupuncture may display the anti-inflammatory and analgesic effects by regulating polarization of T cells in lymph nodes and polarization of M1/M2 macrophages in inflamed joints/paws.In addition,we have spotted a key molecule for acupuncture analgesia,CXCL1,as well as clarified the novel central analgesic mechanism of acupuncture mediated by CXCL1/CXCR2 desensitization.Thereby,we have provided novel evidence of the anti-inflammatory and analgesic actions of acupuncture through regulating NEI network and several key substances,highlighting a systemic research paradigm for investigating mechanisms of acupuncture actions.
