The plant pathogenic fungus Sclerotinia sclerotiorum is the causative agent of Sclerotinia stem rot(SSR)disease in most dicotyledons.Among the various proteins involved in drug efflux or substance transport,ATP-bindin...The plant pathogenic fungus Sclerotinia sclerotiorum is the causative agent of Sclerotinia stem rot(SSR)disease in most dicotyledons.Among the various proteins involved in drug efflux or substance transport,ATP-binding cassette(ABC)transporters constitute a superfamily of membrane-bound proteins that may play a crucial role in the survival of S.sclerotiorum.However,the expression patterns and functions of ABC transporter genes in S.sclerotiorum remain largely uncharacterized.This study characterized a highly expressed S.sclerotiorum ABC transporter gene during inoculation on host plants,Ss BMR1.Silencing Ss BMR1 resulted in a significant reduction in hyphal growth,infection cushion development,sclerotia formation,and virulence.Moreover,host-induced gene silencing(HIGS)of Ss BMR1 significantly enhanced plant resistance.Transcriptome and metabolomics analyses suggested that Ss BMR1 is involved in antioxidant and toxin transport,thereby influencing fungal defense and cell rescue mechanisms.In comparison to the wild-type strain,Ss BMR1 gene-silenced transformants exhibited a diminished response to extracellar oxidative stress and a decreased exporting of antioxidant glutathione.Tolerance assays further demonstrated the crucial role of Ss BMR1 in conferring resistance to the plant antifungal substances,camalexin and brassinin,as well as certain fungicides.Furthermore,Ss BMR1 gene-silenced transformants showed enhanced repression on virulence when sprayed with camalexin and brassinin on the leaves.Thus,Ss BMR1 likely contributes to virulence by facilitating the export of antioxidant and providing resistance against antifungal agents.The findings of this study provide valuable insights that could contribute to the development of novel management techniques for SSR.展开更多
Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and...Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and resources,adding a substantial burden to the healthcare system and patients'families.In this context,chondroitinase ABC,a bacterial enzyme isolated from Proteus vulgaris that is modified to facilitate expression and secretion in mammals,has emerged as a promising therapeutic agent.It works by degrading chondroitin sulfate proteoglycans,cleaving the glycosaminoglycanchains of chondroitin sulfate proteoglycans into soluble disaccharides or tetrasaccharides.Chondroitin sulfate proteoglycans are potent axon growth inhibitors and principal constituents of the extracellular matrix surrounding glial and neuronal cells attached to glycosaminoglycan chains.Chondroitinase ABC has been shown to play an effective role in promoting recovery from acute and chronic spinal cord injury by improving axonal regeneration and sprouting,enhancing the plasticity of perineuronal nets,inhibiting neuronal apoptosis,and modulating immune responses in various animal models.In this review,we introduce the classification and pathological mechanisms of spinal cord injury and discuss the pathophysiological role of chondroitin sulfate proteoglycans in spinal cord injury.We also highlight research advancements in spinal cord injury treatment strategies,with a focus on chondroitinase ABC,and illustrate how improvements in chondroitinase ABC stability,enzymatic activity,and delivery methods have enhanced injured spinal cord repair.Furthermore,we emphasize that combination treatment with chondroitinase ABC further enhances therapeutic efficacy.This review aimed to provide a comprehensive understanding of the current trends and future directions of chondroitinase ABC-based spinal cord injury therapies,with an emphasis on how modern technologies are accelerating the optimization of chondroitinase ABC development.展开更多
A significant number of anticancer drugs fail to treat primary and metastatic brain tumors primarily because of the complex blood-brain barrier(BBB)and overexpression of ATP-binding cassette(ABC)transporters,which dec...A significant number of anticancer drugs fail to treat primary and metastatic brain tumors primarily because of the complex blood-brain barrier(BBB)and overexpression of ATP-binding cassette(ABC)transporters,which decrease drug penetration into the central nervous system and ultimately into tumors.It is noteworthy that the ABC transporters,ABCB1[known as P-glycoprotein(P-gp)]and ABCG2[known as breast cancer resistance protein(BCRP)],are overexpressed in brain tumors,including common gliomas.The co-presence of these transporters may negate the inhibition of either transporter,particularly if both transport the same anticancer drug.The cellular export of drugs by ABC transporters has been implicated in mediating resistance to anticancer drugs.However,the clinical relevance as a therapeutic target in human tumors remains a matter of contention.Although effective and clinically approved ABC transporter inhibitors could potentially overcome drug resistance,none are currently approved.Furthermore,the ABC transporter inhibitors in clinical trials produced low or no clinical efficacy,significant toxicities,and unsuitable pharmacokinetic profiles.Therefore,innovative approaches are needed to efficaciously and simultaneously inhibit these transporters to surmount anticancer drug resistance.This review emphasizes the clinical significance of ABC transporters in diminishing the efficacy of brain tumor treatments.The molecular alterations in BBB following brain tumor development,which are linked to various cancer therapies,are discussed.The overexpression of ABCB1 and ABCG2 at the BBB is discussed,potential strategies to decrease the export of chemotherapeutics by these transporters and the associated challenges and failures are discussed,and the implementation of novel approaches is considered.展开更多
文摘目的探讨基于ABC-X模型的护理干预在轻度认知障碍(mild cognitive impairment,MCI)患者中的应用价值。方法选取100例MCI患者,采用随机数表法将其分为观察组和对照组,各50例。观察组使用基于ABC-X模型的护理干预,对照组使用常规护理干预。比较两组患者干预前和干预4周后的焦虑自评量表(self-rating anxiety scale,SAS)、抑郁自评量表(self-rating depression scale,SDS)、蒙特利尔认知评估(Montreal cognitive assessment,Mo CA)量表、36条简明健康状况调查表(36-item short form health survey,SF-36)评分。结果两组患者在护理干预前SAS、SDS得分、MoCA量表总分、SF-36平均分比较,差异均无统计学意义(均P>0.05)。在干预4周后,观察组患者SAS、SDS得分均显著低于对照组(均P<0.01);Mo CA量表总分、SF-36平均分均显著高于对照组(均P<0.01)。结论在MCI患者中应用基于ABC-X模型的护理干预,能有效缓解其负面情绪,改善认知功能,进而提升其生活质量,因此具备良好的推广应用价值。
基金received financial support from the Natural Science Foundation of Chongqing,China(CSTB2023NSCQMSX0355)the Fundamental Research Funds for the Central Universities,China(SWU120075)the National Natural Science Foundation of China(32372077)。
文摘The plant pathogenic fungus Sclerotinia sclerotiorum is the causative agent of Sclerotinia stem rot(SSR)disease in most dicotyledons.Among the various proteins involved in drug efflux or substance transport,ATP-binding cassette(ABC)transporters constitute a superfamily of membrane-bound proteins that may play a crucial role in the survival of S.sclerotiorum.However,the expression patterns and functions of ABC transporter genes in S.sclerotiorum remain largely uncharacterized.This study characterized a highly expressed S.sclerotiorum ABC transporter gene during inoculation on host plants,Ss BMR1.Silencing Ss BMR1 resulted in a significant reduction in hyphal growth,infection cushion development,sclerotia formation,and virulence.Moreover,host-induced gene silencing(HIGS)of Ss BMR1 significantly enhanced plant resistance.Transcriptome and metabolomics analyses suggested that Ss BMR1 is involved in antioxidant and toxin transport,thereby influencing fungal defense and cell rescue mechanisms.In comparison to the wild-type strain,Ss BMR1 gene-silenced transformants exhibited a diminished response to extracellar oxidative stress and a decreased exporting of antioxidant glutathione.Tolerance assays further demonstrated the crucial role of Ss BMR1 in conferring resistance to the plant antifungal substances,camalexin and brassinin,as well as certain fungicides.Furthermore,Ss BMR1 gene-silenced transformants showed enhanced repression on virulence when sprayed with camalexin and brassinin on the leaves.Thus,Ss BMR1 likely contributes to virulence by facilitating the export of antioxidant and providing resistance against antifungal agents.The findings of this study provide valuable insights that could contribute to the development of novel management techniques for SSR.
基金supported by the National Natural Science Foundation of China,No.82002645China Postdoctoral Science Foundation,No.2022M722321Jiangsu Funding Program for Excellent Postdoctoral Talent,No.2022ZB552(all to YH)。
文摘Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and resources,adding a substantial burden to the healthcare system and patients'families.In this context,chondroitinase ABC,a bacterial enzyme isolated from Proteus vulgaris that is modified to facilitate expression and secretion in mammals,has emerged as a promising therapeutic agent.It works by degrading chondroitin sulfate proteoglycans,cleaving the glycosaminoglycanchains of chondroitin sulfate proteoglycans into soluble disaccharides or tetrasaccharides.Chondroitin sulfate proteoglycans are potent axon growth inhibitors and principal constituents of the extracellular matrix surrounding glial and neuronal cells attached to glycosaminoglycan chains.Chondroitinase ABC has been shown to play an effective role in promoting recovery from acute and chronic spinal cord injury by improving axonal regeneration and sprouting,enhancing the plasticity of perineuronal nets,inhibiting neuronal apoptosis,and modulating immune responses in various animal models.In this review,we introduce the classification and pathological mechanisms of spinal cord injury and discuss the pathophysiological role of chondroitin sulfate proteoglycans in spinal cord injury.We also highlight research advancements in spinal cord injury treatment strategies,with a focus on chondroitinase ABC,and illustrate how improvements in chondroitinase ABC stability,enzymatic activity,and delivery methods have enhanced injured spinal cord repair.Furthermore,we emphasize that combination treatment with chondroitinase ABC further enhances therapeutic efficacy.This review aimed to provide a comprehensive understanding of the current trends and future directions of chondroitinase ABC-based spinal cord injury therapies,with an emphasis on how modern technologies are accelerating the optimization of chondroitinase ABC development.
基金supported by Arkansas Bioscience Institute funds (ABI-GR020025) from University of Arkansas for Medical Sciences
文摘A significant number of anticancer drugs fail to treat primary and metastatic brain tumors primarily because of the complex blood-brain barrier(BBB)and overexpression of ATP-binding cassette(ABC)transporters,which decrease drug penetration into the central nervous system and ultimately into tumors.It is noteworthy that the ABC transporters,ABCB1[known as P-glycoprotein(P-gp)]and ABCG2[known as breast cancer resistance protein(BCRP)],are overexpressed in brain tumors,including common gliomas.The co-presence of these transporters may negate the inhibition of either transporter,particularly if both transport the same anticancer drug.The cellular export of drugs by ABC transporters has been implicated in mediating resistance to anticancer drugs.However,the clinical relevance as a therapeutic target in human tumors remains a matter of contention.Although effective and clinically approved ABC transporter inhibitors could potentially overcome drug resistance,none are currently approved.Furthermore,the ABC transporter inhibitors in clinical trials produced low or no clinical efficacy,significant toxicities,and unsuitable pharmacokinetic profiles.Therefore,innovative approaches are needed to efficaciously and simultaneously inhibit these transporters to surmount anticancer drug resistance.This review emphasizes the clinical significance of ABC transporters in diminishing the efficacy of brain tumor treatments.The molecular alterations in BBB following brain tumor development,which are linked to various cancer therapies,are discussed.The overexpression of ABCB1 and ABCG2 at the BBB is discussed,potential strategies to decrease the export of chemotherapeutics by these transporters and the associated challenges and failures are discussed,and the implementation of novel approaches is considered.
