Background Depression is a common comorbidity in Parkinson's disease(PD)and Lewy body dementia(LBD).However,studies examining the rate of incident depression in the period preceding and following the diagnosis of ...Background Depression is a common comorbidity in Parkinson's disease(PD)and Lewy body dementia(LBD).However,studies examining the rate of incident depression in the period preceding and following the diagnosis of PD and LBD are lacki ng in the literature.Aims To quantify the incidence of depression in the period preceding and following the diagnosis of PD and LBD.Methods We conducted a retrospective case-control study.Specifically,we used Danish registers to identify all patients with a diagnosis of PD or LBD in the period from 2007 to 2019.These patients were matched by age,calendar year of diagnosis and sex with up to three patients diagnosed with rheumatoid arthritis(RA),chronic kidney disease(CKD)or osteoporosis,respectively.The outcome was incident depression.The incidence of depression was assessed for up to 10 years before and up to 10 years after the diagnosis of PD or LBD.Hazard rates of incident depression for patients with PD or LBD,both before and after diagnosis,were compared with those for patients with RA,CKD or osteoporosis using a Coxproportional hazards model.Results We identified 17711 patients with PD or LBD.Their median age was 74.98(68.10-80.85)years,and39.92%were females.These patients were matched to 19556,40842 and 47809 patients with RA,CKD and osteoporosis,respectively.From 7 to 8 years before diagnosis to 5 years after diagnosis,patients with PD and LBD consistently had higher hazard rates of incident depression than all comparator groups.Conclusions These findings are compatible with depression being an early manifestation of the neurodegenerative changes eventually leading to PD and LBD and imply that incident depression at a late age should raise awareness of potential PD and LBD.展开更多
The crosstalk between immune or alveolar epithelial cells and fibroblasts mediated by paracrine signaling molecules is associated with the pathogenesis of idiopathic pulmonary fibrosis(IPF).However,studies investigati...The crosstalk between immune or alveolar epithelial cells and fibroblasts mediated by paracrine signaling molecules is associated with the pathogenesis of idiopathic pulmonary fibrosis(IPF).However,studies investigating the active involvement of soluble mediators derived from bronchial epithelial cells in fibroblast activation and the development of pulmonary fibrosis are limited.Reanalysis of bulk and single-cell RNA-sequencing data from human bronchus and IPF lung tissue revealed marked upregulation of parathyroid hormone-like hormone(PTHLH)in IPF lung tissue compared with normal tissue,with expression predominantly localized to bronchial epithelial cells.parathyroid hormone-related protein(PTHrP)translated from PTHLH was significantly increased in the bronchial epithelium of IPF patients and bleomycin-induced pulmonary fibrosis mice.Furthermore,the paracrine peptide PTHrP1-34,generated through post-translational processing of PTHrP,was elevated in lung homogenates and bronchoalveolar lavage fluid obtained from fibrotic lungs.Cell-and animal-based experiments showed that PTHrP1-34 activated fibroblasts and extracellular matrix production,resulting in the progression of pulmonary fibrosis.In a preclinical evaluation using a bleomycin-induced pulmonary fibrosis mouse model,attenuating effects against pulmonary fibrosis were observed using neutralizing antibodies,peptides,and gene silencing strategies targeting the PTHrP1-34/parathyroid hormone 1 receptor axis.In conclusion,our results suggest that PTHrP1-34 derived from bronchial epithelial cells is involved in the pathogenesis of IPF and is a promising target for alleviating disease progression.展开更多
文摘Background Depression is a common comorbidity in Parkinson's disease(PD)and Lewy body dementia(LBD).However,studies examining the rate of incident depression in the period preceding and following the diagnosis of PD and LBD are lacki ng in the literature.Aims To quantify the incidence of depression in the period preceding and following the diagnosis of PD and LBD.Methods We conducted a retrospective case-control study.Specifically,we used Danish registers to identify all patients with a diagnosis of PD or LBD in the period from 2007 to 2019.These patients were matched by age,calendar year of diagnosis and sex with up to three patients diagnosed with rheumatoid arthritis(RA),chronic kidney disease(CKD)or osteoporosis,respectively.The outcome was incident depression.The incidence of depression was assessed for up to 10 years before and up to 10 years after the diagnosis of PD or LBD.Hazard rates of incident depression for patients with PD or LBD,both before and after diagnosis,were compared with those for patients with RA,CKD or osteoporosis using a Coxproportional hazards model.Results We identified 17711 patients with PD or LBD.Their median age was 74.98(68.10-80.85)years,and39.92%were females.These patients were matched to 19556,40842 and 47809 patients with RA,CKD and osteoporosis,respectively.From 7 to 8 years before diagnosis to 5 years after diagnosis,patients with PD and LBD consistently had higher hazard rates of incident depression than all comparator groups.Conclusions These findings are compatible with depression being an early manifestation of the neurodegenerative changes eventually leading to PD and LBD and imply that incident depression at a late age should raise awareness of potential PD and LBD.
基金supported by the National Research Foundation of Korea(NRF)grants funded by the Korean government(MSIT)(NRF-2022R1A4A3034038,NRF-2021R1F1A1045974,and NRF-2021R1C1C2005646)This research was also supported by the Regional Innovation System&Education(RISE)program through the Chungbuk Regional Innovation System&Education Center,funded by the Ministry of Education(MOE)and Chungcheongbuk-do,Republic of Korea(2025-RISE-11-003-03)In addition,this research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(RS-2024-00439991).
文摘The crosstalk between immune or alveolar epithelial cells and fibroblasts mediated by paracrine signaling molecules is associated with the pathogenesis of idiopathic pulmonary fibrosis(IPF).However,studies investigating the active involvement of soluble mediators derived from bronchial epithelial cells in fibroblast activation and the development of pulmonary fibrosis are limited.Reanalysis of bulk and single-cell RNA-sequencing data from human bronchus and IPF lung tissue revealed marked upregulation of parathyroid hormone-like hormone(PTHLH)in IPF lung tissue compared with normal tissue,with expression predominantly localized to bronchial epithelial cells.parathyroid hormone-related protein(PTHrP)translated from PTHLH was significantly increased in the bronchial epithelium of IPF patients and bleomycin-induced pulmonary fibrosis mice.Furthermore,the paracrine peptide PTHrP1-34,generated through post-translational processing of PTHrP,was elevated in lung homogenates and bronchoalveolar lavage fluid obtained from fibrotic lungs.Cell-and animal-based experiments showed that PTHrP1-34 activated fibroblasts and extracellular matrix production,resulting in the progression of pulmonary fibrosis.In a preclinical evaluation using a bleomycin-induced pulmonary fibrosis mouse model,attenuating effects against pulmonary fibrosis were observed using neutralizing antibodies,peptides,and gene silencing strategies targeting the PTHrP1-34/parathyroid hormone 1 receptor axis.In conclusion,our results suggest that PTHrP1-34 derived from bronchial epithelial cells is involved in the pathogenesis of IPF and is a promising target for alleviating disease progression.
