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Article: Revisiting the Elusive Hepatitis C Vaccine.

Todryk, Stephen M / Bassendine, Margaret F / Bridge, Simon H

2021 Volume 9, Issue 2

Abstract: The impactful discovery and subsequent characterisation of hepatitis C virus (HCV), an RNA virus of the flavivirus family, led to the awarding of the 2020 Nobel Prize in Physiology or Medicine to Harvey J. Alter, Michael Houghton and Charles M. Rice [ ... ] ...

Abstract	The impactful discovery and subsequent characterisation of hepatitis C virus (HCV), an RNA virus of the flavivirus family, led to the awarding of the 2020 Nobel Prize in Physiology or Medicine to Harvey J. Alter, Michael Houghton and Charles M. Rice [...].
Language	English
Publishing date	2021-02-02
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines9020114
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Relapse of polymyalgia rheumatica following adjuvanted influenza vaccine: A case-based review.

Bassendine, Margaret F / Bridge, Simon H

European journal of rheumatology

2019 Volume 7, Issue 1, Page(s) 37–40

Abstract: Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatological condition affecting individuals aged >50 years. There have been rare reports of PMR and other vasculitides developing within 3 months of influenza vaccination. Influenza is a ... ...

Abstract	Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatological condition affecting individuals aged >50 years. There have been rare reports of PMR and other vasculitides developing within 3 months of influenza vaccination. Influenza is a major public health issue associated with seasonal increased mortality and intensified health care service use. Annual vaccination is the most effective intervention to prevent influenza, especially in elderly individuals. We report a severe "flare" of PMR in a 70-year-old patient after receiving the adjuvanted trivalent influenza vaccine, as recommended by the Joint Committee on Vaccination and Immunisations for this age group in the UK National Health Service in 2018-2019. The adverse event (AE) could be interpreted as the newly described autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome) as both PMR and ASIA display hyperactive immune responses. Caution is warranted in the use of vaccine adjuvants in patients with PMR with pre-existing imbalance of B and T cell homeostasis. Rare AEs are important to individuals, and personalized medicine means we should move away from "one size fits all" for vaccines, as well as for therapeutics.
Language	English
Publishing date	2019-12-16
Publishing country	Turkey
Document type	Journal Article ; Review
ZDB-ID	2873727-1
ISSN	2148-4279 ; 2147-9720
ISSN (online)	2148-4279
ISSN	2147-9720
DOI	10.5152/eurjrheum.2019.19152
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Article ; Online: Revisiting the Elusive Hepatitis C Vaccine

Stephen M. Todryk / Margaret F. Bassendine / Simon H. Bridge

Vaccines, Vol 9, Iss 2, p

2021 Volume 114

Abstract	The impactful discovery and subsequent characterisation of hepatitis C virus (HCV), an RNA virus of the flavivirus family, led to the awarding of the 2020 Nobel Prize in Physiology or Medicine to Harvey J [.]
Keywords	n/a ; Medicine ; R
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Is Alzheimer's Disease a Liver Disease of the Brain?

Bassendine, Margaret F / Taylor-Robinson, Simon D / Fertleman, Michael / Khan, Michael / Neely, Dermot

Journal of Alzheimer's disease : JAD

2020 Volume 75, Issue 1, Page(s) 1–14

Abstract: Clinical specialization is not only a force for progress, but it has also led to the fragmentation of medical knowledge. The focus of research in the field of Alzheimer's disease (AD) is neurobiology, while hepatologists focus on liver diseases and lipid ...

Abstract	Clinical specialization is not only a force for progress, but it has also led to the fragmentation of medical knowledge. The focus of research in the field of Alzheimer's disease (AD) is neurobiology, while hepatologists focus on liver diseases and lipid specialists on atherosclerosis. This article on AD focuses on the role of the liver and lipid homeostasis in the development of AD. Amyloid-β (Aβ) deposits accumulate as plaques in the brain of an AD patient long before cognitive decline is evident. Aβ generation is a normal physiological process; the steady-state level of Aβ in the brain is determined by balance between Aβ production and its clearance. We present evidence suggesting that the liver is the origin of brain Aβ deposits and that it is involved in peripheral clearance of circulating Aβ in the blood. Hence the liver could be targeted to decrease Aβ production or increase peripheral clearance.
MeSH term(s)	Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/metabolism ; Animals ; Brain/metabolism ; Brain/pathology ; Humans ; Lipid Metabolism/physiology ; Liver/metabolism ; Liver/pathology ; Metabolic Syndrome/metabolism ; Metabolic Syndrome/pathology
Chemical Substances	Amyloid beta-Peptides ; Amyloid beta-Protein Precursor
Language	English
Publishing date	2020-04-02
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-190848
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Article ; Online: COVID-19 and comorbidities: A role for dipeptidyl peptidase 4 (DPP4) in disease severity?

Bassendine, Margaret F / Bridge, Simon H / McCaughan, Geoffrey W / Gorrell, Mark D

Journal of diabetes

2020 Volume 12, Issue 9, Page(s) 649–658

Abstract: The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to SARS-CoV and Middle East respiratory syndrome (MERS-CoV), which cause acute respiratory ... ...

Abstract	The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to SARS-CoV and Middle East respiratory syndrome (MERS-CoV), which cause acute respiratory distress syndrome and case fatalities. COVID-19 disease severity is worse in older obese patients with comorbidities such as diabetes, hypertension, cardiovascular disease, and chronic lung disease. Cell binding and entry of betacoronaviruses is via their surface spike glycoprotein; SARS-CoV binds to the metalloprotease angiotensin-converting enzyme 2 (ACE2), MERS-CoV utilizes dipeptidyl peptidase 4 (DPP4), and recent modeling of the structure of SARS-CoV-2 spike glycoprotein predicts that it can interact with human DPP4 in addition to ACE2. DPP4 is a ubiquitous membrane-bound aminopeptidase that circulates in plasma; it is multifunctional with roles in nutrition, metabolism, and immune and endocrine systems. DPP4 activity differentially regulates glucose homeostasis and inflammation via its enzymatic activity and nonenzymatic immunomodulatory effects. The importance of DPP4 for the medical community has been highlighted by the approval of DPP4 inhibitors, or gliptins, for the treatment of type 2 diabetes mellitus. This review discusses the dysregulation of DPP4 in COVID-19 comorbid conditions; DPP4 activity is higher in older individuals and increased plasma DPP4 is a predictor of the onset of metabolic syndrome. DPP4 upregulation may be a determinant of COVID-19 disease severity, which creates interest regarding the use of gliptins in management of COVID-19. Also, knowledge of the chemistry and biology of DPP4 could be utilized to develop novel therapies to block viral entry of some betacoronaviruses, potentially including SARS-CoV-2.
MeSH term(s)	COVID-19 ; Comorbidity ; Coronavirus Infections/complications ; Coronavirus Infections/drug therapy ; Dipeptidyl Peptidase 4 ; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use ; Humans ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/drug therapy
Chemical Substances	Dipeptidyl-Peptidase IV Inhibitors ; DPP4 protein, human (EC 3.4.14.5) ; Dipeptidyl Peptidase 4 (EC 3.4.14.5)
Keywords	covid19
Language	English
Publishing date	2020-05-27
Publishing country	Australia
Document type	Journal Article ; Review
ZDB-ID	2503337-2
ISSN	1753-0407 ; 1753-0393
ISSN (online)	1753-0407
ISSN	1753-0393
DOI	10.1111/1753-0407.13052
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Article ; Online: COVID‐19 and comorbidities

Bassendine, Margaret F. / Bridge, Simon H. / McCaughan, Geoffrey W. / Gorrell, Mark D.

Journal of Diabetes

A role for dipeptidyl peptidase 4 ( DPP4 ) in disease severity?

2020 Volume 12, Issue 9, Page(s) 649–658

Keywords	Endocrinology, Diabetes and Metabolism ; covid19
Language	English
Publisher	Wiley
Publishing country	us
Document type	Article ; Online
ZDB-ID	2503337-2
ISSN	1753-0393
ISSN	1753-0393
DOI	10.1111/1753-0407.13052
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis.

Sheridan, David A / Shawa, Isaac Thom / Thomas, E Louise / Felmlee, Daniel J / Bridge, Simon H / Neely, Dermot / Cobbold, Jeremy F / Holmes, Elaine / Bassendine, Margaret F / Taylor-Robinson, Simon D

Scientific reports

2022 Volume 12, Issue 1, Page(s) 5562

Abstract: Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) ... ...

Abstract	Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated with increasing hepatic steatosis. The genotype-specific lipid disturbances may shed light on genotypic variations in liver disease progression and promotion of hepatocellular cancer in HCV-G3.
MeSH term(s)	Cholesterol ; Genotype ; Hepacivirus/genetics ; Hepatitis C ; Humans ; Lipid Metabolism/genetics
Chemical Substances	Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2022-04-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-09588-w
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Article ; Online: Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis

David A. Sheridan / Isaac Thom Shawa / E. Louise Thomas / Daniel J. Felmlee / Simon H. Bridge / Dermot Neely / Jeremy F. Cobbold / Elaine Holmes / Margaret F. Bassendine / Simon D. Taylor-Robinson

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 11

Abstract: Abstract Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 ( ... ...

Abstract	Abstract Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated ...
Keywords	Medicine ; R ; Science ; Q
Subject code	360 ; 570
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: COVID-19 and comorbidities: A role for dipeptidyl peptidase 4 (DPP4) in disease severity?

Bassendine, Margaret F / Bridge, Simon H / McCaughan, Geoffrey W / Gorrell, Mark D

J. diabetes (Online)

Abstract	The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to SARS-CoV and Middle East respiratory syndrome (MERS-CoV), which cause acute respiratory distress syndrome and case fatalities. COVID-19 disease severity is worse in older obese patients with comorbidities such as diabetes, hypertension, cardiovascular disease, and chronic lung disease. Cell binding and entry of betacoronaviruses is via their surface spike glycoprotein; SARS-CoV binds to the metalloprotease angiotensin-converting enzyme 2 (ACE2), MERS-CoV utilizes dipeptidyl peptidase 4 (DPP4), and recent modeling of the structure of SARS-CoV-2 spike glycoprotein predicts that it can interact with human DPP4 in addition to ACE2. DPP4 is a ubiquitous membrane-bound aminopeptidase that circulates in plasma; it is multifunctional with roles in nutrition, metabolism, and immune and endocrine systems. DPP4 activity differentially regulates glucose homeostasis and inflammation via its enzymatic activity and nonenzymatic immunomodulatory effects. The importance of DPP4 for the medical community has been highlighted by the approval of DPP4 inhibitors, or gliptins, for the treatment of type 2 diabetes mellitus. This review discusses the dysregulation of DPP4 in COVID-19 comorbid conditions; DPP4 activity is higher in older individuals and increased plasma DPP4 is a predictor of the onset of metabolic syndrome. DPP4 upregulation may be a determinant of COVID-19 disease severity, which creates interest regarding the use of gliptins in management of COVID-19. Also, knowledge of the chemistry and biology of DPP4 could be utilized to develop novel therapies to block viral entry of some betacoronaviruses, potentially including SARS-CoV-2.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #32394639
Database	COVID19

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Article ; Online: Covid‐19 and co‐morbidities

Bassendine, Margaret F. / Bridge, Simon / McCaughan, Geoffrey W. / Gorrell, Mark D.

a role for Dipeptidyl Peptidase 4 ( DPP4 ) in disease severity?

2020

Abstract: The coronavirus disease 2019 (COVID‐19) pandemic is caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), similar to SARS‐CoV and Middle East respiratory syndrome (MERS‐CoV), which cause acute respiratory ... ...

Abstract	The coronavirus disease 2019 (COVID‐19) pandemic is caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), similar to SARS‐CoV and Middle East respiratory syndrome (MERS‐CoV), which cause acute respiratory distress syndrome and case fatalities. COVID‐19 disease severity is worse in older obese patients with comorbidities such as diabetes, hypertension, cardiovascular disease, and chronic lung disease. Cell binding and entry of betacoronaviruses is via their surface spike glycoprotein; SARS‐CoV binds to the metalloprotease angiotensin‐converting enzyme 2 (ACE2), MERS‐CoV utilizes dipeptidyl peptidase 4 (DPP4), and recent modeling of the structure of SARS‐CoV‐2 spike glycoprotein predicts that it can interact with human DPP4 in addition to ACE2. DPP4 is a ubiquitous membrane‐bound aminopeptidase that circulates in plasma; it is multifunctional with roles in nutrition, metabolism, and immune and endocrine systems. DPP4 activity differentially regulates glucose homeostasis and inflammation via its enzymatic activity and nonenzymatic immunomodulatory effects. The importance of DPP4 for the medical community has been highlighted by the approval of DPP4 inhibitors, or gliptins, for the treatment of type 2 diabetes mellitus. This review discusses the dysregulation of DPP4 in COVID‐19 comorbid conditions; DPP4 activity is higher in older individuals and increased plasma DPP4 is a predictor of the onset of metabolic syndrome. DPP4 upregulation may be a determinant of COVID‐19 disease severity, which creates interest regarding the use of gliptins in management of COVID‐19. Also, knowledge of the chemistry and biology of DPP4 could be utilized to develop novel therapies to block viral entry of some betacoronaviruses, potentially including SARS‐CoV‐2.
Keywords	A100 Pre-clinical Medicine ; C100 Biology ; C700 Molecular Biology ; Biophysics and Biochemistry ; C900 Others in Biological Sciences ; covid19
Subject code	610
Language	English
Publishing date	2020-09-01
Publisher	Wiley-Blackwell
Publishing country	uk
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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