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| 1 | Molecular targets in the treatment of alcoholic hepatitis显示文摘Alcohol related costs to health and society are high. One of the most serious complications of alcohol misuse to the individual is the development of alcoholic hepatitis (AH), a clinical syndrome of jaundice and progressive inflammatory liver injury in patients with a history of recent heavy alcohol use. It has a poor outcome and few existing successful therapies. The use of glucocorticoids in patients with severe AH is still controversial and there remains a group of patients with glucocorticoid-resistant disease. However, as our understanding of the pathogenesis of the condition improves there are opportunities to develop new targeted therapies with specific actions to control liver inflammation without having a detrimental effect on the immune system as a whole. In this article we review the molecular mechanisms of AH concentrating on the activation of the innate and adaptive immune response. We consider existing treatments including glucocorticoids, anti-tumor necrosis factor therapy and pentoxifylline and their limitations. Using our knowledge of the disease pathogenesis we discuss possible novel therapeutic approaches. New targets include pro-inflammatory cytokines such as interleukin (IL)-17, chemokines and their receptors (for example IL-8, CXCL9 and CXCR3) and augmentation of anti-inflam- matory molecules such as IL-10 and IL-22. And there is also future potential to consider combination therapy to selectively modulate the immune response and gain control of disease. | Ashwin D Dhanda Richard WL Lee Peter L Collins C Anne McCune | 2012 | World Journal of Gastroenterology2012，18，39： | 9 |
| 2 | Oxidative stress in alcohol-related liver disease显示文摘Alcohol consumption is one of the leading causes of the global burden of disease and results in high healthcare and economic costs.Heavy alcohol misuse leads to alcohol-related liver disease,which is responsible for a significant proportion of alcohol-attributable deaths globally.Other than reducing alcohol consumption,there are currently no effective treatments for alcohol-related liver disease.Oxidative stress refers to an imbalance in the production and elimination of reactive oxygen species and antioxidants.It plays important roles in several aspects of alcohol-related liver disease pathogenesis.Here,we review how chronic alcohol use results in oxidative stress through increased metabolism via the cytochrome P4502E1 system producing reactive oxygen species,acetaldehyde and protein and DNA adducts.These trigger inflammatory signaling pathways within the liver leading to expression of pro-inflammatory mediators causing hepatocyte apoptosis and necrosis.Reactive oxygen species exposure also results in mitochondrial stress within hepatocytes causing structural and functional dysregulation of mitochondria and upregulating apoptotic signaling.There is also evidence that oxidative stress as well as the direct effect of alcohol influences epigenetic regulation.Increased global histone methylation and acetylation and specific histone acetylation inhibits antioxidant responses and promotes expression of key pro-inflammatory genes.This review highlights aspects of the role of oxidative stress in disease pathogenesis that warrant further study including mitochondrial stress and epigenetic regulation.Improved understanding of these processes may identify novel targets for therapy. | Huey K Tan Euan Yates Kristen Lilly Ashwin D Dhanda | 2020 | World Journal of Hepatology2020，12，7： | 6 |
| 3 | Is liver biopsy necessary in the management of alcoholic hepatitis?显示文摘Acute alcoholic hepatitis(AAH)is characterised by deep jaundice in patients with a history of heavy alcohol use,which can progress to liver failure.A clinical diagnosis of AAH can be challenging to make in patients without a clear alcohol history or in the presence of risk factors for other causes of acute liver failure.Other causes of acute on chronic liver failure such as sepsis or variceal haemorrhage should be considered.Liver biopsy remains the only reliable method to make an accurate diagnosis.However,there is controversy surrounding the use of liver biopsy in patients with AAH because of the risks of performing a percutaneous biopsy and limitations in access to transjugular biopsy.We review the existing literature and find there are few studies directly comparing clinical and histological diagnosis of AAH.In the small number of studies that have been conducted the correlation between a clinical and histological diagnosis of AAH is poor.Due to this lack of agreement together with difficulties in accessing transjugular liver biopsy outside tertiary referral centres and research institutions,we cannot advocate universal biopsy for AAH but there remains a definite role for liver biopsy where there is clinical diagnostic doubt or dual pathology.Italso adds value in a clinical trial context to ensure a homogeneous trial population and to further our understanding of the disease pathology.Further prospective studies are required to determine whether non-invasive markers can be used to accurately diagnose AAH. | Ashwin D Dhanda Peter L Collins C Anne McCune | 2013 | World Journal of Gastroenterology2013，19，44： | 4 |
| 4 | The influence of goat genotype on the production of Capretto and Chevon carcasses. 1. Growth and carcass characteristics显示文摘 | J.S Dhanda D.G Taylor J.E McCosker P.J Murray | 1999 | Meat Science1999，，4： | 3 |
| 5 | Endogenous monitoring and enforcement of a transferable emission permit system显示文摘 | Stranlund J K Dhanda K K | 1999 | Journal of Environmental Economics and Management1999，38，： | 1 |
| 6 | The influence of goat genotype on the production of Capretto and chevon carcasses显示文摘 | Dhanda JS Taylor DG McCosker JE | 1999 | Meat Science1999，52，： | 1 |
| 7 | Cellular protection from oxidative DNA damage by over - expression of the novel globin cytoglobin in vitro 显示文摘 | Hodges NJ Innocent N Dhanda S | 2008 | Mutagenesis2008，23，4： | 1 |
| 8 | Character associations among quantitative and quality attributes of upland cotton显示文摘 | Dhanda S S | 1984 | Indian Journal of Agricultural Science1984，54，1： | 1 |
| 9 | Virusisolation from wild-caught mosquitoes during a Japanses encephalitis outbreak in Keralain 1996 显示文摘 | Dhanda V Thenmozhi V Kurnar N P | 1997 | Indian J Med Res1997，106，： | 1 |
| 10 | Virus isolation from wild-caught mosquitoes during an Japanses encephalitis outbreak in Kerala in 1996显示文摘 | Dhanda V Thenmozhi V Kumar N P | 1997 | Indian J M Res1997，106，： | 1 |
| 11 | A review ofmolecular mechanisms in the development of hepatocellularcarcinoma by aflatoxin and hepatitis B and Gviruses显示文摘 | Moudgil V Redhu D Dhanda S | 2013 | J Environ Pathol Toxicol Oncol2013，32，2： | 1 |
| 12 | The new Wild West is green: carbon offset markets, transactions, and providers显示文摘 | Dhanda Kanwalroop K Murphy Patrick J | 2011 | Academy Of Management Perspectives2011，25，4： | 1 |
| 13 | The ethics of carbon neutrality: A critical examination of voluntary carbon offset providers显示文摘 | Dhanda K Kathy Hartman Laura P | 2011 | Journal of Business Ethics2011，100，1： | 1 |
| 14 | Endogenous Monitoring and Enforcement of a Transferable Emissions Permit System 显示文摘 | Stranlund J K Dhanda K K | 1999 | Journal of Environmental Economics and Management1999，38，： | 1 |
| 15 | Risk of pulmonary com- plications after elective abdominal surgery显示文摘 | Lawrence VA Dhanda R Hilsenbeck SG | 1996 | Chest1996，110，： | 1 |
| 16 | Group A Streptococcus virulence factors genes in north India & their association with emm type in pharyngitis显示文摘 | Dhanda V Vohra H Kumar R | | 0，，： | 1 |
| 17 | Indices of drought tolerance inwheat genotypes at early stages of plant growth显示文摘 | Dhanda S S Sethi G S BehI R K | 2004 | Journal of Agrono-my and Crop Science2004，190，1： | 1 |
| 18 | Group A streptococcus virulence factors genes in North India &their association with emm type in pharyngitis显示文摘 | DHANDA V VOHRA H KUMAR R | 2011 | Indian J Med Res2011，133，133： | 1 |
| 19 | Damage control resuscitation protocol and the management of open abdomens in trauma patients显示文摘 | Bradley M Galvagno S Dhanda A | 2014 | Am Surg2014，80，8： | 1 |
| 20 | Global survey of genetic variation in CCR5 ,RANTES,and MIP- 1 alpha: impact on the epidemiology of the HIV - 1 pandemic 显示文摘 | GONZALEZ E DHANDA R BAMSHAD M | 2001 | Proc Natl Acad Sci U S A2001，98，9： | 1 |
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