Phenylacetaldehyde(PAH),an aromatic compound,is present in a diverse range of fruits including overripe bananas and prickly pear cactus,the two major host fruits for Drosophila melanogaster.PAH acts as a potent ligand...Phenylacetaldehyde(PAH),an aromatic compound,is present in a diverse range of fruits including overripe bananas and prickly pear cactus,the two major host fruits for Drosophila melanogaster.PAH acts as a potent ligand for the ionotropic receptor 84a(IR84a)in the adult fruit fly and it is detected by the IR84a/IR8a heterotetrameric complex.Its role in the male courtship behavior through IR84a as an environmental aphrodisiac is of additional importance.In D.melanogaster,two distinct kinds of olfactory receptors,that is,odorant receptors(ORs)and ionotropic receptors(IRs),perceive the odorant stimuli.They display unique structural,molecular,and functional characteristics in addition to having different evolutionary origins.Traditionally,olfactory cues detected by the ORs such as ethyl acetate,1-butanol,isoamyl acetate,1-octanol,4-methylcyclohexanol,etc.classified as aliphatic esters and alcohols have been employed in olfactory classical conditioning using fruit flies.This underlines the participation of OR-activated olfactory pathways in learning and memory formation.Our study elucidates that likewise ethyl acetate(EA)(an OR-responsive odorant),PAH(an IR-responsive aromatic compound)too can form learning and memory when associated with an appetitive gustatory reinforcer.The association of PAH with sucrose(PAH/SUC)led to learning and formation of the long-term memory(LTM).Additionally,the Orco^(1),Ir84a^(MI00501),and Ir8a^(1)mutant flies were used to confirm the exclusive participation of the IR84a/IR8a complex in PAH/SUC olfactory associative conditioning.These results highlight the involvement of IRs via an IR-activated pathway in facilitating robust olfactory behavior.展开更多
Exosome-based treatments are gaining traction as a viable approach to addressing the various issues faced by an ischemic stroke.These extracellular vesicles,mainly produced by mesenchymal stem cells,exhibit many prope...Exosome-based treatments are gaining traction as a viable approach to addressing the various issues faced by an ischemic stroke.These extracellular vesicles,mainly produced by mesenchymal stem cells,exhibit many properties with substantial therapeutic potential.Exosomes are particularly appealing for stroke therapy because of their low immunogenicity,effective cargo transport,and ability to cross the blood–brain barrier.Their diverse effects include neuroprotection,angiogenesis stimulation,inflammatory response modulation,and cell death pathway attenuation,synergistically promoting neuronal survival,tissue regeneration,and functional recovery.Exosomes also show potential as diagnostic indicators for early stroke identification and customized treatment options.Despite these promising qualities,current exosome-based therapeutics have some limitations.The heterogeneity of exosome release among cell types,difficulty in standardization and isolation techniques,and complications linked to dosage and targeted administration necessitates extensive investigation.It is critical to thoroughly understand exosomal processes and their complicated interactions within the cellular milieu.To improve the practicality and efficacy of exosome-based medicines,research efforts must focus on improving production processes,developing robust evaluation criteria,and developing large-scale isolation techniques.Altogether,exosomes’multifunctional properties offer a new route for transforming stroke treatment and significantly improving patient outcomes.展开更多
Ligation of T cell receptor （TCR） alone is insufficient to induce full activation of T lymphocytes. Additional ligand-receptor interactions （costimulation） on antigen presenting cells （APCs） and T cells are requ...Ligation of T cell receptor （TCR） alone is insufficient to induce full activation of T lymphocytes. Additional ligand-receptor interactions （costimulation） on antigen presenting cells （APCs） and T cells are required. T cell costimulation has been shown to be essential for eliciting efficient T cell responses, involving all phases during T cell development. However, the mechanisms by which costimulation affects the function of T cells still need to be elucidated. In recent years, advances have been made in studies of costimulation as potential therapies in cancer, infectious disease as well as autoimmune disease. In this review, we discussed intracellular costimulation signals that regulate T cell proliferation, cell cycle progression, cytokine production, survival, and memory development. In general, the pathway of phosphoinositide-3 kinase （PI3K）/protein kinase B （PKB, also known as Akt）/nuclear factor κB （NF-κB） might be central to many costimulatory effects. Through these pathways, costimulation controls T-cell expansion and proliferation by maintenance of survivin and aurora B expression, and sustains long-term T-cell survival and memory development by regulating the expression of bcl-2 family members. Cellular ＆ Molecular Immunology. 2008;5（4）：239-247.展开更多
基金funding of Researchers Supporting Project Number(RSPD2023R710)from King Saud University,Riyadh,Saudi Arabia.
文摘Phenylacetaldehyde(PAH),an aromatic compound,is present in a diverse range of fruits including overripe bananas and prickly pear cactus,the two major host fruits for Drosophila melanogaster.PAH acts as a potent ligand for the ionotropic receptor 84a(IR84a)in the adult fruit fly and it is detected by the IR84a/IR8a heterotetrameric complex.Its role in the male courtship behavior through IR84a as an environmental aphrodisiac is of additional importance.In D.melanogaster,two distinct kinds of olfactory receptors,that is,odorant receptors(ORs)and ionotropic receptors(IRs),perceive the odorant stimuli.They display unique structural,molecular,and functional characteristics in addition to having different evolutionary origins.Traditionally,olfactory cues detected by the ORs such as ethyl acetate,1-butanol,isoamyl acetate,1-octanol,4-methylcyclohexanol,etc.classified as aliphatic esters and alcohols have been employed in olfactory classical conditioning using fruit flies.This underlines the participation of OR-activated olfactory pathways in learning and memory formation.Our study elucidates that likewise ethyl acetate(EA)(an OR-responsive odorant),PAH(an IR-responsive aromatic compound)too can form learning and memory when associated with an appetitive gustatory reinforcer.The association of PAH with sucrose(PAH/SUC)led to learning and formation of the long-term memory(LTM).Additionally,the Orco^(1),Ir84a^(MI00501),and Ir8a^(1)mutant flies were used to confirm the exclusive participation of the IR84a/IR8a complex in PAH/SUC olfactory associative conditioning.These results highlight the involvement of IRs via an IR-activated pathway in facilitating robust olfactory behavior.
基金National Institutes of Health,Grant/Award Number:NIH R21NS133531。
文摘Exosome-based treatments are gaining traction as a viable approach to addressing the various issues faced by an ischemic stroke.These extracellular vesicles,mainly produced by mesenchymal stem cells,exhibit many properties with substantial therapeutic potential.Exosomes are particularly appealing for stroke therapy because of their low immunogenicity,effective cargo transport,and ability to cross the blood–brain barrier.Their diverse effects include neuroprotection,angiogenesis stimulation,inflammatory response modulation,and cell death pathway attenuation,synergistically promoting neuronal survival,tissue regeneration,and functional recovery.Exosomes also show potential as diagnostic indicators for early stroke identification and customized treatment options.Despite these promising qualities,current exosome-based therapeutics have some limitations.The heterogeneity of exosome release among cell types,difficulty in standardization and isolation techniques,and complications linked to dosage and targeted administration necessitates extensive investigation.It is critical to thoroughly understand exosomal processes and their complicated interactions within the cellular milieu.To improve the practicality and efficacy of exosome-based medicines,research efforts must focus on improving production processes,developing robust evaluation criteria,and developing large-scale isolation techniques.Altogether,exosomes’multifunctional properties offer a new route for transforming stroke treatment and significantly improving patient outcomes.
基金The project was funded,in part,under grants from the Pennsylvania Department of Health and St.Baldrick's Foundation (J.Song)
文摘Ligation of T cell receptor （TCR） alone is insufficient to induce full activation of T lymphocytes. Additional ligand-receptor interactions （costimulation） on antigen presenting cells （APCs） and T cells are required. T cell costimulation has been shown to be essential for eliciting efficient T cell responses, involving all phases during T cell development. However, the mechanisms by which costimulation affects the function of T cells still need to be elucidated. In recent years, advances have been made in studies of costimulation as potential therapies in cancer, infectious disease as well as autoimmune disease. In this review, we discussed intracellular costimulation signals that regulate T cell proliferation, cell cycle progression, cytokine production, survival, and memory development. In general, the pathway of phosphoinositide-3 kinase （PI3K）/protein kinase B （PKB, also known as Akt）/nuclear factor κB （NF-κB） might be central to many costimulatory effects. Through these pathways, costimulation controls T-cell expansion and proliferation by maintenance of survivin and aurora B expression, and sustains long-term T-cell survival and memory development by regulating the expression of bcl-2 family members. Cellular ＆ Molecular Immunology. 2008;5（4）：239-247.
