Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
Activation of myeloid cells by human endogenous retroviral entities:While the exact causes of neurological diseases such as multiple sclerosis(MS)or amyotrophic lateral sclerosis(ALS)are still elusive,there is evidenc...Activation of myeloid cells by human endogenous retroviral entities:While the exact causes of neurological diseases such as multiple sclerosis(MS)or amyotrophic lateral sclerosis(ALS)are still elusive,there is evidence of a new category of pathogenic elements called human endogenous retroviruses(HERVs)which seem to contribute to their evolution and progression by exerting inflammatory and degenerative effects(Kury et al.,2018).HERVs are ancient retroviral elements which account for up to 8%of the human genome and it is known that environmental factors can trigger their(re-)expression(Kury et al.,2018).The resulting production of viral particles and/or proteins,especially from members of the HERV-W and HERV-K family,is strongly correlated with the onset and progression of neurological diseases,such as MS and ALS(Kury et al.,2018).展开更多
Butein,a rare chalcone found in the toxic plant Toxicodendron vernicifluum,has been shown to regulate glucose homeostasis via inhibition of the nuclear factor kappa-B kinase subunit beta(IKKβ)/nuclear factor kappa B(...Butein,a rare chalcone found in the toxic plant Toxicodendron vernicifluum,has been shown to regulate glucose homeostasis via inhibition of the nuclear factor kappa-B kinase subunit beta(IKKβ)/nuclear factor kappa B(NF-κB)pathway in the brain.Here,we investigated whether the nonpoisonous plant Dahlia pinnata could be a source of butein as a potential treatment for type 2 diabetes(T2D).In mice fed a high-fat diet(HFD)to induce glucose intolerance,an oral D.pinnata petal extract improved glucose tolerance at doses of 3.3 mg/kg body weight and 10 mg/kg body weight.Surprisingly,this effect was not mediated by butein alone but by butein combined with the closely related flavonoids,sulfuretin and/or isoliquiritigenin.Mechanistically,the extract improved systemic insulin tolerance.Inhibition of phosphatidylinositol 3-kinase to block insulin signaling in the brain abrogated the glucoregulatory effect of the orally administered extract.The extract reinstated central insulin signaling and normalized astrogliosis in the hypothalamus of HFD-fed mice.Using NF-κB reporter zebrafish to determine IKKβ/NF-κB activity,a potent anti-inflammatory action of the extract was found.A randomized controlled crossover clinical trial on participants with predia-betes or T2D confirmed the safety and efficacy of the extract in humans.In conclusion,we identified an extract from the flower petals of D.pinnata as a novel treatment option for T2D,potentially targeting the central regulation of glucose homeostasis as a root cause of the disease.展开更多
基金supported by the Christiane and Claudia Hempel Foundation for Regenerative Medicineby the James and Elisabeth Cloppenburg, Peek and Cloppenburg Düsseldorf Stiftung(to PK)。
文摘Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
基金supported by the French societies ARSEP(Fondation pour l’Aideàla Recherche sur la Sclérose en Plaques)and AFM(Association Fran?aise Contre les Myopathies)DMSG Ortsvereinigung Düsseldorf und Umgebung e.V.as well as by Geneuro.JG is a student of the i Brain graduate school+2 种基金PK and JG are supported by the Stifterverband/NovartisstiftungDK was funded by the Deutsche Forschungsgemeinschaft(DFG)while carrying research on HERVs at Cleveland ClinicThe MS Center at the Department of Neurology is supported in part by the Walter and Ilse Rose Foundation and the James and Elisabeth Cloppenburg,Peek,and Cloppenburg Düsseldorf Stiftung
文摘Activation of myeloid cells by human endogenous retroviral entities:While the exact causes of neurological diseases such as multiple sclerosis(MS)or amyotrophic lateral sclerosis(ALS)are still elusive,there is evidence of a new category of pathogenic elements called human endogenous retroviruses(HERVs)which seem to contribute to their evolution and progression by exerting inflammatory and degenerative effects(Kury et al.,2018).HERVs are ancient retroviral elements which account for up to 8%of the human genome and it is known that environmental factors can trigger their(re-)expression(Kury et al.,2018).The resulting production of viral particles and/or proteins,especially from members of the HERV-W and HERV-K family,is strongly correlated with the onset and progression of neurological diseases,such as MS and ALS(Kury et al.,2018).
基金For mice,all procedures were approved by the UoO Animal Ethics Committee.For humans,the trial(registration number U1111-1201-6917)was approved by the NZ Ministry of Health,Central Health and Disability Ethics Committee(17/CEN/194)in line with the guidelines of the Declarations of Helsinki and Tokyo.
文摘Butein,a rare chalcone found in the toxic plant Toxicodendron vernicifluum,has been shown to regulate glucose homeostasis via inhibition of the nuclear factor kappa-B kinase subunit beta(IKKβ)/nuclear factor kappa B(NF-κB)pathway in the brain.Here,we investigated whether the nonpoisonous plant Dahlia pinnata could be a source of butein as a potential treatment for type 2 diabetes(T2D).In mice fed a high-fat diet(HFD)to induce glucose intolerance,an oral D.pinnata petal extract improved glucose tolerance at doses of 3.3 mg/kg body weight and 10 mg/kg body weight.Surprisingly,this effect was not mediated by butein alone but by butein combined with the closely related flavonoids,sulfuretin and/or isoliquiritigenin.Mechanistically,the extract improved systemic insulin tolerance.Inhibition of phosphatidylinositol 3-kinase to block insulin signaling in the brain abrogated the glucoregulatory effect of the orally administered extract.The extract reinstated central insulin signaling and normalized astrogliosis in the hypothalamus of HFD-fed mice.Using NF-κB reporter zebrafish to determine IKKβ/NF-κB activity,a potent anti-inflammatory action of the extract was found.A randomized controlled crossover clinical trial on participants with predia-betes or T2D confirmed the safety and efficacy of the extract in humans.In conclusion,we identified an extract from the flower petals of D.pinnata as a novel treatment option for T2D,potentially targeting the central regulation of glucose homeostasis as a root cause of the disease.
