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Enhanced mitophagy in bronchial fibroblasts from severe asthmatic patients

Ramakrishnan, Rakhee K. ; Bajbouj, Khuloud ; Hachim, Mahmood Y. ; [et al.]

Public Library of Science (PLoS) ; 2020

In: PLOS ONE Vol. 15, No. 11 ( 2020-11-30), p. e0242695-

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In: PLOS ONE, Public Library of Science (PLoS), Vol. 15, No. 11 ( 2020-11-30), p. e0242695-

Abstract: Sub-epithelial fibrosis is a characteristic feature of airway remodeling in asthma which correlates with disease severity. Current asthma medications are ineffective in treating fibrosis. In this study, we aimed to investigate the mitochondrial phenotype in fibroblasts isolated from airway biopsies of non-asthmatic and severe asthmatic subjects by examining mitophagy as a mechanism contributing to fibroblast persistence and thereby, fibrosis in severe asthma. Methods Bioinformatics analysis of publicly available transcriptomic data was performed to identify the top enriched pathways in asthmatic fibroblasts. Endogenous expression of mitophagy markers in severe asthmatic and non-asthmatic fibroblasts was determined using qRT-PCR, western blot and immunofluorescence. Mitophagy flux was examined by using lysosomal protease inhibitors, E64d and pepstatin A. Mitochondrial membrane potential and metabolic activity were also evaluated using JC-1 assay and MTT assay, respectively. Results Bioinformatics analysis revealed the enrichment of Pink/Parkin-mediated mitophagy in asthmatic fibroblasts compared to healthy controls. In severe asthmatic fibroblasts, the differential expression of mitophagy genes, PINK1 and PRKN, was accompanied by the accumulation of PINK1, Parkin and other mitophagy proteins at baseline. The further accumulation of endogenous LC3BII, p62 and PINK1 in the presence of E64d and pepstatin A in severe asthmatic fibroblasts reinforced their enhanced mitophagy flux. Significantly reduced mitochondrial membrane potential and metabolic activity were also demonstrated at baseline confirming the impairment in mitochondrial function in severe asthmatic fibroblasts. Interestingly, these fibroblasts displayed neither an apoptotic nor senescent phenotype but a pro-fibrotic phenotype with an adaptive survival mechanism triggered by increased AMPKα phosphorylation and mitochondrial biogenesis. Conclusions Our results demonstrated a role for mitophagy in the pathogenesis of severe asthma where the enhanced turnover of damaged mitochondria may contribute to fibrosis in severe asthma by promoting the persistence and pro-fibrotic phenotype of fibroblasts.

Type of Medium: Online Resource

ISSN: 1932-6203

URL: Article

DOI: 10.1371/journal.pone.0242695

DOI: 10.1371/journal.pone.0242695.g001

DOI: 10.1371/journal.pone.0242695.g002

DOI: 10.1371/journal.pone.0242695.g003

DOI: 10.1371/journal.pone.0242695.g004

DOI: 10.1371/journal.pone.0242695.g005

DOI: 10.1371/journal.pone.0242695.g006

DOI: 10.1371/journal.pone.0242695.g007

DOI: 10.1371/journal.pone.0242695.t001

DOI: 10.1371/journal.pone.0242695.s001

DOI: 10.1371/journal.pone.0242695.s002

DOI: 10.1371/journal.pone.0242695.s003

DOI: 10.1371/journal.pone.0242695.r001

DOI: 10.1371/journal.pone.0242695.r002

DOI: 10.1371/journal.pone.0242695.r003

DOI: 10.1371/journal.pone.0242695.r004

DOI: 10.1371/journal.pone.0242695.r005

DOI: 10.1371/journal.pone.0242695.r006

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2020

detail.hit.zdb_id: 2267670-3

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Dysphagie sicher einordnen, Versorgung koordinieren : Erstdiagnostik

Ott, Roland ; Bajbouj, M. ; Feussner, H. ; [et al.]

Springer Science and Business Media LLC ; 2014

In: MMW - Fortschritte der Medizin Vol. 156, No. 7 ( 2014-4), p. 54-58

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In: MMW - Fortschritte der Medizin, Springer Science and Business Media LLC, Vol. 156, No. 7 ( 2014-4), p. 54-58

Type of Medium: Online Resource

ISSN: 1438-3276 , 1613-3560

URL: Article

DOI: 10.1007/s15006-014-2922-0

Language: German

Publisher: Springer Science and Business Media LLC

Publication Date: 2014

detail.hit.zdb_id: 2173071-4

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P.645 Immune cell-type specific methylation of tissue-type plasminogen activator in patients receiving electroconvulsive therapy

Moschny, N. ; Jahn, K. ; Maier, H. ; [et al.]

Elsevier BV ; 2019

In: European Neuropsychopharmacology Vol. 29 ( 2019-12), p. S438-S439

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In: European Neuropsychopharmacology, Elsevier BV, Vol. 29 ( 2019-12), p. S438-S439

Type of Medium: Online Resource

ISSN: 0924-977X

URL: Article

DOI: 10.1016/j.euroneuro.2019.09.622

Language: English

Publisher: Elsevier BV

Publication Date: 2019

detail.hit.zdb_id: 2019305-1

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Mindfulness-based group therapy for inpatients with schizophrenia spectrum disorders – feasibility, acceptability, and preliminary outcomes of a rater-blinded randomized controlled trial

Böge, K. ; Hahne, I.M. ; Bergmann, N. ; [et al.]

Royal College of Psychiatrists ; 2021

In: European Psychiatry Vol. 64, No. S1 ( 2021-04), p. S805-S806

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In: European Psychiatry, Royal College of Psychiatrists, Vol. 64, No. S1 ( 2021-04), p. S805-S806

Abstract: The therapeutic effectiveness of mindfulness-based interventions (MBIs) has been shown for various mental disorders. However, for schizophrenia spectrum disorders (SSD), only a few trials have been conducted, mostly in outpatient settings. Objectives This study aimed to investigate feasibility, acceptability, and preliminary effectiveness of a four-week mindfulness-based group therapy (MBGT) for in-patients with SSD. Methods A pre-registered randomized controlled trial (RCT) was conducted at the in-patient ward for SSD. All measures were employed at baseline, post-intervention (4-weeks), and follow-up (12-weeks). The primary outcome was ‘mindfulness’. Secondary outcomes were rater-blinded positive- and negative symptoms, depression, social functioning, as well as self-rated mindfulness, depression, anxiety, psychological flexibility, quality of life, and medication regime. Results N=40 participants were randomized into either four-week treatment-as-usual (TAU; n=19) or MBGT+TAU (n = 21). Protocol adherence was 95.2%, and the retention rate to treatments was 95%. ANCOVA analysis revealed significant improvements in the MBGT+TAU compared to TAU for the primary outcome and negative symptoms. Exploratory analyses showed medium-to-large intervention effects on secondary outcomes mindfulness, positive, negative, and depressive symptoms, psychological flexibility, quality of life, and social functioning for MBGT+TAU and small-to-moderate changes on positive symptoms and social functioning for TAU. No serious adverse effects were reported. Conclusions This study supports the feasibility and acceptability of MBGT for in-patients with SSD, including high protocol adherence and retention rates. A proof of concept of the MBIs and corresponding improvements on various clinical and process parameters warrant a fully powered RCT to determine effectiveness, cost-efficiency, and longitudinal outcomes of MBGT for SSD. Disclosure No significant relationships.

Type of Medium: Online Resource

ISSN: 0924-9338 , 1778-3585

URL: Article

DOI: 10.1192/j.eurpsy.2021.2130

RVK:

XA 10000

Language: English

Publisher: Royal College of Psychiatrists

Publication Date: 2021

detail.hit.zdb_id: 2005377-0

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Vagus nerve stimulation for depression: efficacy and safety in a European study

Schlaepfer, T. E. ; Frick, C. ; Zobel, A. ; [et al.]

Cambridge University Press (CUP) ; 2008

In: Psychological Medicine Vol. 38, No. 5 ( 2008-05), p. 651-661

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In: Psychological Medicine, Cambridge University Press (CUP), Vol. 38, No. 5 ( 2008-05), p. 651-661

Abstract: Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression. Method An open, uncontrolled European multi-centre study (D03) of VNS therapy was conducted, in addition to stable pharmacotherapy, in 74 patients with treatment-resistant depression (TRD). Treatment remained unchanged for the first 3 months; in the subsequent 9 months, medications and VNS dosing parameters were altered as indicated clinically. Results The baseline 28-item Hamilton Depression Rating Scale (HAMD-28) score averaged 34. After 3 months of VNS, response rates (⩾50% reduction in baseline scores) reached 37% and remission rates (HAMD-28 score 〈 10) 17%. Response rates increased to 53% after 1 year of VNS, and remission rates reached 33%. Response was defined as sustained if no relapse occurred during the first year of VNS after response onset; 44% of patients met these criteria. Median time to response was 9 months. Most frequent side-effects were voice alteration (63% at 3 months of stimulation) and coughing (23%). Conclusions VNS therapy was effective in reducing severity of depression; efficacy increased over time. Efficacy ratings were in the same range as those previously reported from a USA study using a similar protocol; at 12 months, reduction of symptom severity was significantly higher in the European sample. This might be explained by a small but significant difference in the baseline HAMD-28 score and the lower number of treatments in the current episode in the European study.

Type of Medium: Online Resource

ISSN: 0033-2917 , 1469-8978

URL: Article

DOI: 10.1017/S0033291707001924

RVK:

XA 10000

Language: English

Publisher: Cambridge University Press (CUP)

Publication Date: 2008

detail.hit.zdb_id: 1470300-2

SSG: 5,2

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Effects of Mindfulness Training on Emotion Regulation in Patients With Depression: Reduced Dorsolateral Prefrontal Cortex Activation Indexes Early Beneficial Changes

Barnhofer, Thorsten ; Reess, Tim J. ; Fissler, Maria ; [et al.]

Ovid Technologies (Wolters Kluwer Health) ; 2021

In: Psychosomatic Medicine Vol. 83, No. 6 ( 2021-7), p. 579-591

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In: Psychosomatic Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 83, No. 6 ( 2021-7), p. 579-591

Abstract: Mindfulness-based interventions (MBIs) have been found to be a promising approach for the treatment of recurrent courses of depression. However, little is known about their neural mechanisms. This functional magnetic resonance imaging study set out to investigate activation changes in corticolimbic regions during implicit emotion regulation. Methods Depressed patients with a recurrent lifetime history were randomized to receive a 2-week MBI ( n = 16 completers) or psychoeducation and resting (PER; n = 22 completers). Before and after, patients underwent functional magnetic resonance imaging while labeling the affect of angry, happy, and neutral facial expressions and completed questionnaires assessing ruminative brooding, the ability to decenter from such thinking, and depressive symptoms. Results Activation decreased in the right dorsolateral prefrontal cortex (dlPFC) in response to angry faces after MBI ( p 〈 .01, voxel-wise family-wise error rate correction, T 〉 3.282; 56 mm 3 ; Montreal Neurological Institute peak coordinate: 32, 24, 40), but not after PER. This change was highly correlated with increased decentring ( r = −0.52, p = .033), decreased brooding ( r = 0.60, p = .010), and decreased symptoms ( r = 0.82, p = .005). Amygdala activation in response to happy faces decreased after PER ( p 〈 .01, family-wise error rate corrected; 392 mm 3 ; Montreal Neurological Institute peak coordinate: 28, −4, −16), whereas the MBI group showed no significant change. Conclusions The dlPFC is involved in emotion regulation, namely, reappraisal or suppression of negative emotions. Decreased right dlPFC activation might indicate that, after the MBI, patients abstained from engaging in elaboration or suppression of negative affective stimuli; a putatively important mechanism for preventing the escalation of negative mood. Trial Registration: The study is registered at ClinicalTrials.gov (NCT02801513; 16/06/2016).

Type of Medium: Online Resource

ISSN: 1534-7796 , 0033-3174

URL: Article

DOI: 10.1097/PSY.0000000000000955

RVK:

XA 10000

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2021

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Association of the G1947A COMT (Val108/158Met) gene polymorphism with prefrontal P300 during information processing

Gallinat, J ; Bajbouj, M ; Sander, T ; [et al.]

Georg Thieme Verlag KG ; 2004

In: Pharmacopsychiatry Vol. 36, No. 05 ( 2004-6-9)

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In: Pharmacopsychiatry, Georg Thieme Verlag KG, Vol. 36, No. 05 ( 2004-6-9)

Type of Medium: Online Resource

ISSN: 0176-3679 , 1439-0795

URL: Issue

URL: Journal

URL: Article

DOI: 10.1055/s-002-2876

DOI: 10.1055/s-00000054

DOI: 10.1055/s-2003-825332

RVK:

XA 10000

Language: English

Publisher: Georg Thieme Verlag KG

Publication Date: 2004

detail.hit.zdb_id: 2041961-2

SSG: 15,3

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Endoskopische Vollwandresektion nach R1-Resektion eines neuroendokrinen Tumors im Rektum unter Verwendung eines neuen Over-the-scope Device

Klare, P ; Burlefinger, R ; Neu, B ; [et al.]

Georg Thieme Verlag KG ; 2015

In: Endoskopie heute Vol. 28, No. 01 ( 2015-3-9)

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In: Endoskopie heute, Georg Thieme Verlag KG, Vol. 28, No. 01 ( 2015-3-9)

Type of Medium: Online Resource

ISSN: 0933-811X , 1439-2577

URL: Issue

URL: Journal

URL: Article

DOI: 10.1055/s-005-28756

DOI: 10.1055/s-00000013

DOI: 10.1055/s-0035-1545054

Language: German

Publisher: Georg Thieme Verlag KG

Publication Date: 2015

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Vergleich der pharyngealen Säuremessung mit den Ergebnissen der Impedanzmessung bei Patienten mit klinischem Verdacht auf einen laryngo-pharyngealen Reflux

Wosch, K ; Becker, V ; Golluscio, R ; [et al.]

Georg Thieme Verlag KG ; 2010

In: Zeitschrift für Gastroenterologie Vol. 48, No. 10 ( 2010-10)

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In: Zeitschrift für Gastroenterologie, Georg Thieme Verlag KG, Vol. 48, No. 10 ( 2010-10)

Type of Medium: Online Resource

ISSN: 0044-2771 , 1439-7803

URL: Article

DOI: 10.1055/s-0030-1267699

RVK:

XA 10000

Language: German

Publisher: Georg Thieme Verlag KG

Publication Date: 2010

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Diagnostischer Nutzen der Kappen-assistierten Ösophago-Gastro-Duodenoskopie zur Beurteilung der Papilla duodeni major: eine Prospektive, Randomisierte und blinde Crossover Studie (κ-Studie)

Abdelhafez, M ; Phillip, V ; Hapfelmeier, A ; [et al.]

Georg Thieme Verlag KG ; 2017

In: Zeitschrift für Gastroenterologie Vol. 55, No. 05 ( 2017-5-9), p. e1-e27

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In: Zeitschrift für Gastroenterologie, Georg Thieme Verlag KG, Vol. 55, No. 05 ( 2017-5-9), p. e1-e27

Type of Medium: Online Resource

ISSN: 0044-2771 , 1439-7803

URL: Article

DOI: 10.1055/s-0037-1603036

RVK:

XA 10000

Language: German

Publisher: Georg Thieme Verlag KG

Publication Date: 2017

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