LIVIVO - Search results -

Search results

Result 1 - 10 of total 31

Search options

Article ; Online: Review article: epidemiology, pathogenesis and management of liver disease in adults with cystic fibrosis.

Scott, Jennifer / Jones, Andrew M / Piper Hanley, Karen / Athwal, Varinder S

2022 Volume 55, Issue 4, Page(s) 389–400

Abstract: Background: Cystic fibrosis-related liver disease (CFLD) is the leading cause of death in cystic fibrosis (CF), after pulmonary disease. To improve identification and management of this condition requires an understanding of the underlying disease ... ...

Abstract	Background: Cystic fibrosis-related liver disease (CFLD) is the leading cause of death in cystic fibrosis (CF), after pulmonary disease. To improve identification and management of this condition requires an understanding of the underlying disease mechanism. Aims: This review summarises the current understanding of CFLD epidemiology, pathology, diagnosis and management. Methods: Relevant reports on cystic fibrosis liver disease were identified using a literature search and summarised. Results: CFLD is a heterogeneous condition with several different co-existent pathologies, including environmental and genetic factors. Incidence of clinically significant CFLD continues at a linear rate into early adulthood and has been described in up to 25% of CF patients. Diagnosis strategies lack precision and patient risk stratification needs to look beyond Childs-Pugh scoring. Efficacious therapies are lacking and, at present, newer modulator therapies lack data in CFLD and carry an increased risk of hepatotoxicity. Outcomes of liver transplant are comparable to non-CF transplant indications. Conclusions: The incidence of CFLD increases with age and hence is increasingly important to adult patients with CF. Effective therapies are lacking. For progress to be made a better understanding of pathogenesis and disease detection are required.
MeSH term(s)	Adult ; Child ; Cystic Fibrosis/complications ; Cystic Fibrosis/epidemiology ; Cystic Fibrosis/therapy ; Humans ; Incidence ; Liver Diseases/complications ; Liver Diseases/epidemiology ; Liver Diseases/therapy ; Liver Transplantation/adverse effects
Language	English
Publishing date	2022-01-19
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	639012-2
ISSN	1365-2036 ; 0269-2813 ; 0953-0673
ISSN (online)	1365-2036
ISSN	0269-2813 ; 0953-0673
DOI	10.1111/apt.16749
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2206: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article: Unlocking the post-transplant microenvironment for successful islet function and survival.

Doherty, Daniel T / Khambalia, Hussein A / van Dellen, David / Jennings, Rachel E / Piper Hanley, Karen

Frontiers in endocrinology

2023 Volume 14, Page(s) 1250126

Abstract: Islet transplantation (IT) offers the potential to restore euglycemia for patients with type 1 diabetes mellitus (T1DM). Despite improvements in islet isolation techniques and immunosuppressive regimes, outcomes remain suboptimal with UK five-year graft ... ...

Abstract	Islet transplantation (IT) offers the potential to restore euglycemia for patients with type 1 diabetes mellitus (T1DM). Despite improvements in islet isolation techniques and immunosuppressive regimes, outcomes remain suboptimal with UK five-year graft survivals (5YGS) of 55% and most patients still requiring exogenous insulin after multiple islet infusions. Native islets have a significant non-endocrine component with dense extra-cellular matrix (ECM), important for islet development, cell survival and function. Collagenase isolation necessarily disrupts this complex islet microenvironment, leaving islets devoid of a supporting framework and increasing vulnerability of transplanted islets. Following portal venous transplantation, a liver injury response is potentially induced, which typically results in inflammation and ECM deposition from liver specific myofibroblasts. The impact of this response may have important impact on islet survival and function. A fibroblast response and ECM deposition at the kidney capsule and eye chamber alongside other implantation sites have been shown to be beneficial for survival and function. Investigating the implantation site microenvironment and the interactions of transplanted islets with ECM proteins may reveal therapeutic interventions to improve IT and stem-cell derived beta-cell therapy.
MeSH term(s)	Humans ; Cell Survival ; Diabetes Mellitus, Type 1/surgery ; Extracellular Matrix ; Extracellular Matrix Proteins ; Fibroblasts
Chemical Substances	Extracellular Matrix Proteins
Language	English
Publishing date	2023-08-29
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1250126
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Changes in lung epithelial cell volatile metabolite profile induced by pro-fibrotic stimulation with TGF-

Hayton, Conal / Ahmed, Waqar / Cunningham, Peter / Piper-Hanley, Karen / Pearmain, Laurence / Chaudhuri, Nazia / Leonard, Colm / Blaikley, John F / Fowler, Stephen J

Journal of breath research

2023 Volume 17, Issue 4

Abstract: Volatile organic compounds (VOCs) have shown promise as potential biomarkers in idiopathic pulmonary fibrosis. Measuring VOCs in the headspace ... ...

Abstract	Volatile organic compounds (VOCs) have shown promise as potential biomarkers in idiopathic pulmonary fibrosis. Measuring VOCs in the headspace of
MeSH term(s)	Humans ; Transforming Growth Factor beta1 ; Volatile Organic Compounds ; Breath Tests ; Epithelial Cells ; Idiopathic Pulmonary Fibrosis ; Lung
Chemical Substances	Transforming Growth Factor beta1 ; Volatile Organic Compounds
Language	English
Publishing date	2023-09-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2381007-5
ISSN	1752-7163 ; 1752-7155
ISSN (online)	1752-7163
ISSN	1752-7155
DOI	10.1088/1752-7163/acf391
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Genetic Contribution to Non-alcoholic Fatty Liver Disease and Prognostic Implications.

Martin, Katherine / Hatab, Anas / Athwal, Varinder S / Jokl, Elliot / Piper Hanley, Karen

Current diabetes reports

2021 Volume 21, Issue 3, Page(s) 8

Abstract: Purpose of review: Non-alcoholic fatty liver disease (NAFLD) is a major and increasing health burden, with the potential to overwhelm hepatology services. However, only a minority of patients develop advanced liver disease. The challenge is early ... ...

Abstract	Purpose of review: Non-alcoholic fatty liver disease (NAFLD) is a major and increasing health burden, with the potential to overwhelm hepatology services. However, only a minority of patients develop advanced liver disease. The challenge is early identification of patients at risk of progression. This review aims to summarize current knowledge on the genetic predisposition to NAFLD, and its implications for prognostication and risk stratification. Recent findings: PNPLA3-I148M is the most robustly associated genetic variant with NAFLD. Recently, variants in TM6SF2, MBOAT7, GCKR and HSD17B13 have also been implicated. NAFLD is a complex disease, and any one genetic variant alone is insufficient for risk stratification, but combining multiple genetic variants with other parameters is a promising strategy. It is anticipated that, in the near future, analysis of data from large-scale prospective cohorts will reveal NAFLD subtypes and enable the development of prognostic models. This will facilitate risk stratification of patients, enabling optimisation of resources to effectively manage the NAFLD epidemic.
MeSH term(s)	Genetic Predisposition to Disease ; Humans ; Liver ; Non-alcoholic Fatty Liver Disease/genetics ; Polymorphism, Single Nucleotide ; Prognosis ; Prospective Studies
Language	English
Publishing date	2021-02-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2065167-3
ISSN	1539-0829 ; 1534-4827
ISSN (online)	1539-0829
ISSN	1534-4827
DOI	10.1007/s11892-021-01377-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5628: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Health Technology Adoption in Liver Disease: Innovative Use of Data Science Solutions for Early Disease Detection.

Bennett, Lucy / Purssell, Huw / Street, Oliver / Piper Hanley, Karen / Morling, Joanne R / Hanley, Neil A / Athwal, Varinder / Guha, Indra Neil

Frontiers in digital health

2022 Volume 4, Page(s) 737729

Abstract: Chronic liver disease (CLD) is an ignored epidemic. Premature mortality is considerable and in the United Kingdom (UK) liver disease is in the top three for inequitable healthcare alongside heart and respiratory disease. Fifty percentage of patients with ...

Abstract	Chronic liver disease (CLD) is an ignored epidemic. Premature mortality is considerable and in the United Kingdom (UK) liver disease is in the top three for inequitable healthcare alongside heart and respiratory disease. Fifty percentage of patients with CLD are first diagnosed with cirrhosis after an emergency presentation translating to poorer patient outcomes. Traditional models of care have been based in secondary care when the need is at community level. Investigating patients for disease based on their risk factors at a population level in the community will identify its presence early when there is potential reversibility. Innovation is needed in three broad areas to improve clinical care in this area: better access to diagnostics within the community, integrating diagnostics across primary and secondary care and utilizing digital healthcare to enhance patient care. In this article, we describe how the Integrated Diagnostics for Early Detection of Liver Disease (ID-LIVER) project, funded by UK Research and Innovation, is developing solutions in Greater Manchester to approach the issue of diagnosis of liver disease at a population level. The ambition is to build on innovative pathways previously established in Nottingham by bringing together NHS organizations, academic partners and commercial organizations. The motivation is to co-create and implement a commercial solution that integrates multimodal diagnostics via cutting edge data science to drive growth and disrupt the currently inadequate model. The ambitious vision is for this to be widely adopted for early diagnosis and stratification of liver disease at a population level within the NHS.
Language	English
Publishing date	2022-01-28
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-253X
ISSN (online)	2673-253X
DOI	10.3389/fdgth.2022.737729
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Improving detection of cystic fibrosis related liver disease using liver fibrosis assessment tools.

Scott, Jennifer A / Jones, Andrew M / Jokl, Elliot / Gordon-Walker, Timothy / Barry, Peter J / Hanley, Neil A / Piper Hanley, Karen / Athwal, Varinder S

Heliyon

2023 Volume 9, Issue 11, Page(s) e21861

Abstract: Background & aims: Cystic Fibrosis related liver disease (CFLD) is the 3rd largest cause of death in Cystic Fibrosis (CF). As advances in pulmonary therapies have increased life-expectancy, CFLD has become more prevalent. Current guidelines may ... ...

Abstract	Background & aims: Cystic Fibrosis related liver disease (CFLD) is the 3rd largest cause of death in Cystic Fibrosis (CF). As advances in pulmonary therapies have increased life-expectancy, CFLD has become more prevalent. Current guidelines may underdiagnose liver fibrosis, particularly in its early stages. Newer modalities for the assessment of fibrosis may provide a more accurate assessment. FibroScan is validated in assessing fibrosis for several aetiologies including alcohol and fatty liver, the CFLD cohort have an entirely different phenotype so the cut off values are not transferrable. We appraised fibrosis assessment tools to improve diagnosis of CFLD. Methods: A prospective cohort (n = 114) of patients from the Manchester Adult Cystic Fibrosis Centre, UK were identified at annual assessment. Demographic data including co-morbidity, Results: 12 of 114 patient classified as CFLD according to the European Cystic Fibrosis Society best practice guidelines. No specific risk factors for development of CFLD were identified. Liver enzymes were elevated in patients with CFLD. Serum biomarker panels did not improve diagnostic criteria. LSM accurately predicted CFLD. A new diagnostic criterion was proposed and validated in a separate cohort, accurately predicating CFLD in 10 of 32 patients (31 %). Conclusion: We present a cohort of patients with CF assessed for the presence of liver fibrosis using blood biomarkers and LSM based platforms. We propose a new, simplified diagnostic criteria, capable of accurately predicting liver disease in patients with CF.Clinical trials number: NCT04277819.
Language	English
Publishing date	2023-11-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e21861
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Circadian Disruption Primes Myofibroblasts for Accelerated Activation as a Mechanism Underpinning Fibrotic Progression in Non-Alcoholic Fatty Liver Disease.

Jokl, Elliot / Llewellyn, Jessica / Simpson, Kara / Adegboye, Oluwatobi / Pritchett, James / Zeef, Leo / Donaldson, Ian / Athwal, Varinder S / Purssell, Huw / Street, Oliver / Bennett, Lucy / Guha, Indra Neil / Hanley, Neil A / Meng, Qing-Jun / Piper Hanley, Karen

Cells

2023 Volume 12, Issue 12

Abstract: Circadian rhythm governs many aspects of liver physiology and its disruption exacerbates chronic disease. CLOCKΔ19 mice disrupted circadian rhythm and spontaneously developed obesity and metabolic syndrome, a phenotype that parallels the progression of ... ...

Abstract	Circadian rhythm governs many aspects of liver physiology and its disruption exacerbates chronic disease. CLOCKΔ19 mice disrupted circadian rhythm and spontaneously developed obesity and metabolic syndrome, a phenotype that parallels the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD represents an increasing health burden with an estimated incidence of around 25% and is associated with an increased risk of progression towards inflammation, fibrosis and carcinomas. Excessive extracellular matrix deposition (fibrosis) is the key driver of chronic disease progression. However, little attention was paid to the impact of disrupted circadian rhythm in hepatic stellate cells (HSCs) which are the primary mediator of fibrotic ECM deposition. Here, we showed in vitro and in vivo that liver fibrosis is significantly increased when circadian rhythm is disrupted by CLOCK mutation. Quiescent HSCs from CLOCKΔ19 mice showed higher expression of RhoGDI pathway components and accelerated activation. Genes altered in this primed CLOCKΔ19 qHSC state may provide biomarkers for early liver disease detection, and include AOC3, which correlated with disease severity in patient serum samples. Integration of CLOCKΔ19 microarray data with ATAC-seq data from WT qHSCs suggested a potential CLOCK regulome promoting a quiescent state and downregulating genes involved in cell projection assembly. CLOCKΔ19 mice showed higher baseline COL1 deposition and significantly worse fibrotic injury after CCl
MeSH term(s)	Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism ; Myofibroblasts/metabolism ; Liver Cirrhosis/genetics ; Liver Cirrhosis/pathology ; Circadian Rhythm/genetics
Language	English
Publishing date	2023-06-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12121582
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: PAK1-dependent mechanotransduction enables myofibroblast nuclear adaptation and chromatin organization during fibrosis.

Jokl, Elliot / Mullan, Aoibheann F / Simpson, Kara / Birchall, Lindsay / Pearmain, Laurence / Martin, Katherine / Pritchett, James / Raza, Sayyid / Shah, Rajesh / Hodson, Nigel W / Williams, Craig J / Camacho, Elizabeth / Zeef, Leo / Donaldson, Ian / Athwal, Varinder S / Hanley, Neil A / Piper Hanley, Karen

Cell reports

2023 Volume 42, Issue 11, Page(s) 113414

Abstract: Myofibroblasts are responsible for scarring during fibrosis. The scar propagates mechanical signals inducing a radical transformation in myofibroblast cell state and increasing profibrotic phenotype. Here, we show mechanical stress from progressive ... ...

Abstract	Myofibroblasts are responsible for scarring during fibrosis. The scar propagates mechanical signals inducing a radical transformation in myofibroblast cell state and increasing profibrotic phenotype. Here, we show mechanical stress from progressive scarring induces nuclear softening and de-repression of heterochromatin. The parallel loss of H3K9Me3 enables a permissive state for distinct chromatin accessibility and profibrotic gene regulation. Integrating chromatin accessibility profiles with RNA expression provides insight into the transcription network underlying the switch in profibrotic myofibroblast states, emphasizing mechanoadaptive regulation of PAK1 as key drivers. Through genetic manipulation in liver and lung fibrosis, loss of PAK1-dependent signaling impairs the mechanoadaptive response in vitro and dramatically improves fibrosis in vivo. Moreover, we provide human validation for mechanisms underpinning PAK1-mediated mechanotransduction in liver and lung fibrosis. Collectively, these observations provide insight into the nuclear mechanics driving the profibrotic chromatin landscape in fibrosis, highlighting actomyosin-dependent mechanisms as potential therapeutic targets in fibrosis.
MeSH term(s)	Humans ; Myofibroblasts/pathology ; Pulmonary Fibrosis/pathology ; Cell Differentiation ; Mechanotransduction, Cellular ; Cicatrix/pathology ; Fibrosis ; Chromatin/metabolism ; p21-Activated Kinases/metabolism
Chemical Substances	Chromatin ; PAK1 protein, human (EC 2.7.11.1) ; p21-Activated Kinases (EC 2.7.11.1)
Language	English
Publishing date	2023-11-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.113414
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: SOX9-regulated matrix proteins predict poor outcomes in patients with COVID-19 and pulmonary fibrosis

Pearmain, Laurence / Jokl, Elliot / Simpson, Kara / Birchall, Lindsay / Ou, Yaqing / Lawless, Craig / Simpson, Angela / Mann, Elizabeth / Scott, Nicholas A / Shah, Rajesh / Venkateswaran, Rajamiyer / Stanel, Stefan / Hayton, Conal / Rivera-Ortega, Pilar / Hansbro, Philip / Hanley, Neil / Blaikley, John A / Piper Hanley, Karen

bioRxiv

Abstract: Pulmonary fibrosis is an increasing and major cause of death worldwide. Understanding the cellular and molecular mechanisms underlying the pathophysiology of lung fibrosis may lead to urgently needed diagnostic and prognostic strategies for the disease. ... ...

Abstract	Pulmonary fibrosis is an increasing and major cause of death worldwide. Understanding the cellular and molecular mechanisms underlying the pathophysiology of lung fibrosis may lead to urgently needed diagnostic and prognostic strategies for the disease. SOX9 is a core transcription factor that has been associated with fibrotic disease, however its role and regulation in acute lung injury and/or fibrosis have not been fully defined. In this study we apply a hypothesis based approach to uncover unique SOX9-protein signatures associated with both acute lung injury and fibrotic progression. Using in vivo models of lung injury in the presence or absence of SOX9, our study shows SOX9 is essential to the damage associated response of alveolar epithelial cells from an early time-point in lung injury. In parallel, as disease progresses, SOX9 is responsible for regulating tissue damaging ECM production from pro-fibrotic fibroblasts. In determining the in vivo role of SOX9 we identified secreted ECM components downstream of SOX9 as markers of acute lung injury and fibrosis. To underscore the translational potential of our SOX9-regulated markers, we analysed serum samples from acute COVID19, post COVID19 and idiopathic pulmonary fibrosis (IPF) patient cohorts. Our hypothesis driven SOX9-panels showed significant capability in all cohorts at identifying patients who had poor disease outcomes. This study shows that SOX9 is functionally critical to disease in acute lung injury and pulmonary fibrosis and its regulated pathways have diagnostic, prognostic and therapeutic potential in both COVID19 and IPF disease.
Keywords	covid19
Language	English
Publishing date	2024-01-23
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.01.21.576509
Database	COVID19

Full text online

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: SOX9 is required for kidney fibrosis and activates NAV3 to drive renal myofibroblast function.

Raza, Sayyid / Jokl, Elliot / Pritchett, James / Martin, Katherine / Su, Kim / Simpson, Kara / Birchall, Lindsay / Mullan, Aoibheann F / Athwal, Varinder S / Doherty, Daniel T / Zeef, Leo / Henderson, Neil C / Kalra, Philip A / Hanley, Neil A / Piper Hanley, Karen

Science signaling

2021 Volume 14, Issue 672

Abstract: Renal fibrosis is a common end point for kidney injury and many chronic kidney diseases. Fibrogenesis depends on the sustained activation of myofibroblasts, which deposit the extracellular matrix that causes progressive scarring and organ failure. Here, ... ...

Abstract	Renal fibrosis is a common end point for kidney injury and many chronic kidney diseases. Fibrogenesis depends on the sustained activation of myofibroblasts, which deposit the extracellular matrix that causes progressive scarring and organ failure. Here, we showed that the transcription factor SOX9 was associated with kidney fibrosis in humans and required for experimentally induced kidney fibrosis in mice. From genome-wide analysis, we identified Neuron navigator 3 (NAV3) as acting downstream of SOX9 in kidney fibrosis. NAV3 increased in abundance and colocalized with SOX9 after renal injury in mice, and both SOX9 and NAV3 were present in diseased human kidneys. In an in vitro model of renal pericyte transdifferentiation into myofibroblasts, we demonstrated that NAV3 was required for multiple aspects of fibrogenesis, including actin polymerization linked to cell migration and sustained activation of the mechanosensitive transcription factor YAP1. In summary, our work identifies a SOX9-NAV3-YAP1 axis involved in the progression of kidney fibrosis and points to NAV3 as a potential target for pharmacological intervention.
MeSH term(s)	Animals ; Fibrosis ; Kidney ; Kidney Diseases/genetics ; Kidney Diseases/pathology ; Mice ; Myofibroblasts/pathology ; Signal Transduction
Language	English
Publishing date	2021-03-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2417226-1
ISSN	1937-9145 ; 1945-0877
ISSN (online)	1937-9145
ISSN	1945-0877
DOI	10.1126/scisignal.abb4282
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito