S-adenosylmethionine and proliferation: new pathways, new targets

SAMe (S-adenosylmethionine) is the main methyl donor group in the cell. MAT (methionine adenosyltransferase) is the unique enzyme responsible for the synthesis of SAMe from methionine and ATP, and SAMe is the common point between the three principal metabolic pathways: polyamines, transmethylation and transsulfuration that converge into the methionine cycle. SAMe is now also considered a key regulator of metabolism, proliferation, differentiation, apoptosis and cell death. Recent results show a new signalling pathway implicated in the proliferation of the hepatocyte, where AMPK (AMP-activated protein kinase) and HuR, modulated by SAMe, take place in HGF (hepatocyte growth factor)-mediated cell growth. Abnormalities in methionine metabolism occur in several animal models of alcoholic liver injury, and it is also altered in patients with liver disease. Both high and low levels of SAMe predispose to liver injury. In this regard, knockout mouse models have been developed for the enzymes responsible for SAMe synthesis and catabolism, MAT1A and GNMT (glycine N-methyltransferase) respectively. These knockout mice develop steatosis and HCC (hepatocellular carcinoma), and both models closely replicate the pathologies of human disease, which makes them extremely useful to elucidate the mechanism underlying liver disease. These new findings open a wide range of possibilities to discover novel targets for clinical applications.

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Detection and characterization of Leptospira spp. in dogs diagnosed with kidney and/or liver disease in Selangor, Malaysia

Journal of Veterinary Diagnostic Investigation ◽

10.1177/10406387211024575 ◽

2021 ◽

pp. 104063872110245

Author(s):

Sabri A. Rahman ◽

Kuan H. Khor ◽

Siti Khairani-Bejo ◽

Seng F. Lau ◽

Mazlina Mazlan ◽

...

Keyword(s):

Liver Disease ◽

Mortality Rate ◽

Direct Detection ◽

Bacterial Disease ◽

Pathogenic Leptospira ◽

Wide Range ◽

Leptospira Spp ◽

Rrna Sequencing ◽

The Common

Leptospirosis is a serious bacterial disease that affects both humans and animals. A wide range of symptoms have been described in humans; the disease in dogs is commonly associated with kidney and/or liver disease. In Malaysia, information about the common serovars infecting dogs is limited. Therefore, we investigated the occurrences of leptospirosis in 124 pet dogs diagnosed with kidney and/or liver disease. Blood, urine, abdominal effusion, and/or kidney and liver were collected from the dogs. Based on microscopic agglutination testing, 53 of 124 (42.7%) dogs were seropositive for leptospiral exposure. Sera were frequently positive to serovars Bataviae ( n = 12), Javanica ( n = 10), and Icterohaemorrhagiae ( n = 10). Direct detection using PCR showed that 42 of 124 (33.9%) of the whole blood and 36 of 113 (31.9%) urine samples were positive for pathogenic Leptospira spp. By PCR, 2 of 23 (9.1%) kidney and 2 of 23 (9.1%) liver were positive for pathogenic Leptospira spp. Abdominal effusion from 4 dogs were PCR-positive for pathogenic Leptospira spp. The species detected were L. interrogans, L. borgpetersenii, L. kirschneri, and L. kmetyi by partial 16S rRNA sequencing. We further identified and characterized 11 Leptospira spp. isolates from 8 dogs as serovars Bataviae, Javanica, and Australis. The mortality rate of the Leptospira-infected dogs was high (18 of 53; 34%).

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Interaction of volatile organic compounds and underlying liver disease: a new paradigm for risk

Biological Chemistry ◽

10.1515/hsz-2017-0324 ◽

2018 ◽

Vol 399 (11) ◽

pp. 1237-1248 ◽

Cited By ~ 12

Author(s):

Anna L. Lang ◽

Juliane I. Beier

Keyword(s):

Liver Disease ◽

Liver Injury ◽

Acute Liver Injury ◽

Industrial Chemicals ◽

New Paradigm ◽

Alcoholic Fatty Liver ◽

Underlying Liver Disease ◽

Volatile Organic ◽

Occupational Cohort ◽

Alcoholic Fatty Liver Disease

Abstract Occupational and environmental exposures to industrial chemicals are known to cause hepatotoxicity and liver injury, in humans and in animal models. Historically, research has focused on severe acute liver injury (e.g. fulminant liver failure) or endstage diseases (e.g. cirrhosis and HCC). However, it has become recently recognized that toxicants can cause more subtle changes to the liver. For example, toxicant-associated steatohepatitis, characterized by hepatic steatosis, and inflammation, was recently recognized in an occupational cohort exposed to vinyl chloride. At high occupational levels, toxicants are sufficient to cause liver damage and disease even in healthy subjects with no comorbidities for liver injury. However, it is still largely unknown how exposure to toxicants initiate and possibly more importantly exacerbate liver disease, when combined with other factors, such as underlying non-alcoholic fatty liver disease caused by poor diet and/or obesity. With better understanding of the mechanism(s) and risk factors that mediate the initiation and progression of toxicant-induced liver disease, rational targeted therapy can be developed to better predict risk, as well as to treat or prevent this disease. The purpose of this review is to summarize established and proposed mechanisms of volatile organic compound-induced liver injury and to highlight key signaling events known or hypothesized to mediate these effects.

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Liver injury in COVID-19: The current evidence

United European Gastroenterology Journal ◽

10.1177/2050640620924157 ◽

2020 ◽

Vol 8 (5) ◽

pp. 509-519 ◽

Cited By ~ 22

Author(s):

Saleh A Alqahtani ◽

Jörn M Schattenberg

Keyword(s):

Liver Disease ◽

Liver Injury ◽

Liver Function ◽

Case Series ◽

Current Evidence ◽

Disease Course ◽

Underlying Liver Disease ◽

Hepatobiliary Complications ◽

Novel Coronavirus ◽

Work Up

Patients with novel coronavirus disease 2019 (COVID-19) experience various degrees of liver function abnormalities. Liver injury requires extensive work-up and continuous surveillance and can be multifactorial and heterogeneous in nature. In the context of COVID-19, clinicians will have to determine whether liver injury is related to an underlying liver disease, drugs used for the treatment of COVID-19, direct effect of the virus, or a complicated disease course. Recent studies proposed several theories on potential mechanisms of liver injury in these patients. This review summarizes current evidence related to hepatobiliary complications in COVID-19, provides an overview of the available case series and critically elucidates the proposed mechanisms and provides recommendations for clinicians.

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Herbal Products: Benefits, Limits, and Applications in Chronic Liver Disease

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/837939 ◽

2012 ◽

Vol 2012 ◽

pp. 1-19 ◽

Cited By ~ 31

Author(s):

Anna Del Prete ◽

Antonella Scalera ◽

Maddalena Diana Iadevaia ◽

Agnese Miranda ◽

Claudio Zulli ◽

...

Keyword(s):

Liver Disease ◽

Chronic Liver Disease ◽

Biological Properties ◽

Chronic Liver ◽

Herbal Products ◽

Beneficial Effects ◽

Wide Range ◽

The Common ◽

Proof Of Efficacy ◽

Natural Way

Complementary and alternative medicine soughts and encompasses a wide range of approaches; its use begun in ancient China at the time of Xia dynasty and in India during the Vedic period, but thanks to its long-lasting curative effect, easy availability, natural way of healing, and poor side-effects it is gaining importance throughout the world in clinical practice. We conducted a review describing the effects and the limits of using herbal products in chronic liver disease, focusing our attention on those most known, such as quercetin or curcumin. We tried to describe their pharmacokinetics, biological properties, and their beneficial effects (as antioxidant role) in metabolic, alcoholic, and viral hepatitis (considering that oxidative stress is the common pathway of chronic liver diseases of different etiology). The main limit of applicability of CAM comes from the lacking of randomized, placebo-controlled clinical trials giving a real proof of efficacy of those products, so that anecdotal success and personal experience are frequently the driving force for acceptance of CAM in the population.

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Liver Injury in Patients with COVID-19 without Underlying Liver Disease

Journal of Clinical Medicine ◽

10.3390/jcm11020308 ◽

2022 ◽

Vol 11 (2) ◽

pp. 308

Author(s):

Monika Pazgan-Simon ◽

Sylwia Serafińska ◽

Michał Kukla ◽

Marta Kucharska ◽

Jolanta Zuwała-Jagiełło ◽

...

Keyword(s):

Liver Disease ◽

Liver Injury ◽

Vascular Endothelial Cells ◽

Signs And Symptoms ◽

Liver Function Tests ◽

Underlying Mechanism ◽

Underlying Liver Disease ◽

Pattern Of Injury ◽

Laboratory Test Results ◽

Type Pattern

SARS-CoV-2 shows a high affinity for the ACE-2 receptor, present on the epithelial cells of the upper and lower respiratory tract, within the intestine, kidneys, heart, testes, biliary epithelium, and—where it is particularly challenging—on vascular endothelial cells. Liver involvement is a rare manifestation of COVID-19. Material and Methods: We reviewed 450 patients admitted due to the fact of SARS-CoV-2 infection (COVID-19) including 88 with liver injury. Based on medical history and previous laboratory test results, we excluded cases of underlying liver disease. The analysis involved a clinical course of COVID-19 in patients without underlying liver disease as well as the type and course of liver injury. Results: Signs and symptoms of liver injury were present in 20% of patients, mostly presenting as a mixed-type pattern of injury with less common cases of standalone hepatocellular (parenchymal) or cholestatic injury. The liver injury symptoms resolved at the end of inpatient treatment in 20% of cases. Sixteen patients died with no cases where liver injury would be deemed a cause of death. Conclusions: (1) Liver injury secondary to COVID-19 was mild, and in in 20%, the signs and symptoms of liver injury resolved by the end of hospitalization. (2) It seems that liver injury in patients with COVID-19 was not associated with a higher risk of mortality. (3) The underlying mechanism of liver injury as well as its sequelae are not fully known. Therefore, caution and further monitoring are advised, especially in patients whose liver function tests have not returned to normal values.

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Detection and characterisation of Leptospira spp. in dogs diagnosed with kidney and/or liver disease

10.21203/rs.3.rs-36936/v1 ◽

2020 ◽

Author(s):

Mohammad Sabri Abdul Rahman ◽

Kuan Hua Khor ◽

Siti Khairani Bejo ◽

Seng Fong Lau ◽

Mazlina Mazlan ◽

...

Keyword(s):

Liver Disease ◽

Direct Detection ◽

Agglutination Test ◽

Bacterial Disease ◽

Chain Reaction ◽

Tissue Samples ◽

Wide Range ◽

Rrna Sequencing ◽

The Common ◽

Polymerase Chain

Abstract Background Leptospirosis is a zoonotic bacterial disease that affects both humans and animals. In humans, a wide range of symptoms had been described but in dogs, it is commonly associated with kidney and/or liver disease. In Malaysia, information with regards to the common serovars causing leptospiral infection in dogs remains limited. Therefore, this study investigated the occurrences of leptospiral infection in 124 pet dogs diagnosed with kidney and/or liver disease in Malaysia. Results Based on microscopic agglutination test, 42.7% (53/124) of the dogs were seropositive for leptospiral infection. The predominant serovars detected were Bataviae (n = 12), Javanica (n = 10) and Icterohaemorrhagiae (n = 10). The direct detection using polymerase chain reaction showed that 33.9% (42/124) of the whole blood and 31.9% (36/113) of the urine samples were positive to pathogenic Leptospira spp. For tissue samples, 9.1% (2/23) of the kidney and 9.1% (2/23) of liver were positive for pathogenic Leptospira spp. Addition samples of abdominal effusion from four dogs were positive for pathogenic Leptospira spp. The species detected were L. interrogans, L. borgpetersenii, L. kirshneri and L. kmetyi by partial 16S rRNA sequencing. In this study, 11 Leptospira spp. isolated successfully from the eight dogs were further identified and characterised as Bataviae, Javanica and Australis. Unfortunately, the mortality rate of the infected dogs was high at 34.0% (18/53). Conclusions This study allowed for greater understanding of canine leptospirosis through the provision of crucial diagnostic confirmation.

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Liver Disease

Integrative Gastroenterology ◽

10.1093/med/9780190933043.003.0023 ◽

2019 ◽

pp. 485-508

Author(s):

Catiele Antunes ◽

Alia S. Dadabhai

Keyword(s):

Liver Disease ◽

Liver Injury ◽

Liver Failure ◽

Liver Diseases ◽

The Internet ◽

Milk Thistle ◽

Mechanism Of Injury ◽

Wide Range ◽

Natural Remedies ◽

Standard Medical Treatment

Herbal and dietary supplements (HDS) have been increasingly popularized by the internet to augment or serve as alternatives to standard medical treatment in a variety of diseases. With respect to the liver, milk thistle is among the most popular, but a wide range of other therapies are also being used to treat liver diseases, from fatty liver to viral hepatitis. In this chapter, the effects of natural remedies on the liver are outlined as solo or complementary therapies. Hepatotoxicity and acute liver failure from unregulated use of these HDS are also discussed. Natural alternatives used to treat other medical conditions that can adversely affect the liver (via metabolic breakdown or direct hepatic injury) are summarized, along with the proposed mechanism of injury. Increased awareness on the part of the hepatologist or PCP to include an HDS evaluation can be a valuable tool to treat and diagnose liver injury.

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THE ADORNMENTS OF SCYTHIAN AGE OF THE POPULATION OF FOREST-STEPPE: INTRODUCTION TO THE TOPIC ON THE MATERIALS FROM DNIEPER LEFT-BANK AREA

Archaeology and Early History of Ukraine ◽

10.37445/adiu.2021.03.14 ◽

2021 ◽

Vol 40 (3) ◽

pp. 215-224

Author(s):

Y. M. Khodukina

Keyword(s):

Material Culture ◽

Forest Steppe ◽

Left Bank ◽

New Findings ◽

Wide Range ◽

Ancient Times ◽

The Common ◽

And Function ◽

Technological Methods ◽

Sex And Age Differences

This paper focuses on the pins and earrings as the most popular and diverse type of Scythian jewelry. They are exactly the chronological and cultural markers used by researchers in the reconstruction of migrations and connections of the forest-steppe population. The adornments in ancient times, as well as nowadays, were one of the main cultural and social identity markers. First, they have been studied both in the context of the Scythian material remnants and the unique local variants. Vladimira Petrenko was one of the first who made the typology of these artifacts which led to the change in the field. Soon, new findings were discovered that developed the typology of the artifacts, which was based on the local variants and peculiar decorations, e. g. earrings. The common feature of the modern research is to lessen the number of taxa in the typological scheme and determine the precise and rare indicators of the type origin. Even though the adornment of Scythian Age were studied just as a part of the material culture, the consensus of the academia shows that jewelries can represent a wide range of social and cultural processes in ancient communities. Usually, the Scythian adornments are found in the burial and settled sites. Such material remnants combined with the anthropological data and certain fixation can enlarge our understanding of the usage and function of these artifacts. Furthermore, they give us knowledge of the possible popular costume of the time, the sex and age differences in fashion. In addition, new finds from the settlements widen the source base. The analysis of the jewelries in the context of the settlement structures gives a more precise chronology and modes of production. Today, it is sure that the main three technological methods were welding, casting, and smiting. Each method related to the distinct forms and metals the item was made of.

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