scholarly journals Emerging role of circadian clock disruption in alcohol-induced liver disease

2018 ◽  
Vol 315 (3) ◽  
pp. G364-G373 ◽  
Author(s):  
Shannon M. Bailey
Keyword(s):  
Liver Disease ◽  
Circadian Clock ◽  
Therapeutic Approaches ◽  
Excessive Alcohol Consumption ◽  
Peripheral Tissues ◽  
New Therapeutic Approaches ◽  
Timing System ◽  
Excessive Alcohol ◽  
The Impact

The detrimental health effects of excessive alcohol consumption are well documented. Alcohol-induced liver disease (ALD) is the leading cause of death from chronic alcohol use. As with many diseases, the etiology of ALD is influenced by how the liver responds to other secondary insults. The molecular circadian clock is an intrinsic cellular timing system that helps organisms adapt and synchronize metabolism to changes in their environment. The clock also influences how tissues respond to toxic, environmental, and metabolic stressors, like alcohol. Consistent with the essential role for clocks in maintaining health, genetic and environmental disruption of the circadian clock contributes to disease. While a large amount of rich literature is available showing that alcohol disrupts circadian-driven behaviors and that circadian clock disruption increases alcohol drinking and preference, very little is known about the role circadian clocks play in alcohol-induced tissue injuries. In this review, recent studies examining the effect alcohol has on the circadian clock in peripheral tissues (liver and intestine) and the impact circadian clock disruption has on development of ALD are presented. This review also highlights some of the rhythmic metabolic processes in the liver that are disrupted by alcohol and potential mechanisms through which alcohol disrupts the liver clock. Improved understanding of the mechanistic links between the circadian clock and alcohol will hopefully lead to the development of new therapeutic approaches for treating ALD and other alcohol-related organ pathologies.

scholarly journals Pathogenesis of Ischemic Stroke: Role of Epigenetic Mechanisms

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 89 ◽  
Author(s):  
Rosita Stanzione ◽  
Maria Cotugno ◽  
Franca Bianchi ◽  
Simona Marchitti ◽  
Maurizio Forte ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Epigenetic Modifications ◽  
Review Article ◽  
Epigenetic Changes ◽  
Therapeutic Approaches ◽  
Nutritional Factors ◽  
New Therapeutic Approaches ◽  
Different Types ◽  
The Impact

Epigenetics is the branch of molecular biology that studies modifications able to change gene expression without altering the DNA sequence. Epigenetic modulations include DNA methylation, histone modifications, and noncoding RNAs. These gene modifications are heritable and modifiable and can be triggered by lifestyle and nutritional factors. In recent years, epigenetic changes have been associated with the pathogenesis of several diseases such as diabetes, obesity, renal pathology, and different types of cancer. They have also been related with the pathogenesis of cardiovascular diseases including ischemic stroke. Importantly, since epigenetic modifications are reversible processes they could assist with the development of new therapeutic approaches for the treatment of human diseases. In the present review article, we aim to collect the most recent evidence concerning the impact of epigenetic modifications on the pathogenesis of ischemic stroke in both animal models and humans.

scholarly journals Alcohol-Related Liver Disease: Basic Mechanisms and Clinical Perspectives

2021 ◽  
Vol 22 (10) ◽  
pp. 5170
Author(s):  
Szu-Yi Liu ◽  
I-Ting Tsai ◽  
Yin-Chou Hsu
Keyword(s):  
Liver Disease ◽  
Liver Steatosis ◽  
Diagnostic Tools ◽  
Therapeutic Approaches ◽  
Excessive Alcohol Consumption ◽  
Non Invasive ◽  
Cell Based Therapy ◽  
Alcohol Abstinence ◽  
Excessive Alcohol ◽  
Related Liver Disease

Alcohol-related liver disease (ALD) refers to the liver damage occurring due to excessive alcohol consumption and involves a broad spectrum of diseases that includes liver steatosis, steatohepatitis, hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The progression of ALD is mainly associated with the amount and duration of alcohol usage; however, it is also influenced by genetic, epigenetic, and environmental factors. The definite diagnosis of ALD is based on a liver biopsy, although several non-invasive diagnostic tools and serum biomarkers have emerging roles in the early detection of ALD. While alcohol abstinence and nutritional support remain the cornerstone of ALD treatment, growing evidence has revealed that the therapeutic agents that target oxidative stress or gut-liver axis, inflammatory response inhibition, and liver regeneration enhancement also play a role in ALD management. Furthermore, microRNAs modulation and mesenchymal stem cell-based therapy have emerging potential as ALD therapeutic options. This review summarizes the updated understanding of the pathophysiology, diagnosis, and novel therapeutic approaches for ALD.

scholarly journals The emerging role of mechanical and topographical factors in the development and treatment of nervous system disorders: dark and light sides of the force

2021 ◽  
Author(s):  
Natalia Bryniarska-Kubiak ◽  
Andrzej Kubiak ◽  
Małgorzata Lekka ◽  
Agnieszka Basta-Kaim
Keyword(s):  
Nervous System ◽  
Physical Factors ◽  
Nervous System Diseases ◽  
Therapeutic Approaches ◽  
System Disease ◽  
New Therapeutic Approaches ◽  
The Subject ◽  
Topographical Factors ◽  
New Treatment

AbstractNervous system diseases are the subject of intensive research due to their association with high mortality rates and their potential to cause irreversible disability. Most studies focus on targeting the biological factors related to disease pathogenesis, e.g. use of recombinant activator of plasminogen in the treatment of stroke. Nevertheless, multiple diseases such as Parkinson’s disease and Alzheimer’s disease still lack successful treatment. Recently, evidence has indicated that physical factors such as the mechanical properties of cells and tissue and topography play a crucial role in homeostasis as well as disease progression. This review aims to depict these factors’ roles in the progression of nervous system diseases and consequently discusses the possibility of new therapeutic approaches. The literature is reviewed to provide a deeper understanding of the roles played by physical factors in nervous system disease development to aid in the design of promising new treatment approaches. Graphic abstract

scholarly journals Specialized Pro-Resolving Lipid Mediators in Neonatal Cardiovascular Physiology and Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 933
Author(s):  
Andrea Gila-Diaz ◽  
Gloria Herranz Carrillo ◽  
Pratibha Singh ◽  
David Ramiro-Cortijo
Keyword(s):  
Tissue Repair ◽  
Cardiovascular Health ◽  
Critical Role ◽  
Potential Effect ◽  
Lipid Mediators ◽  
Physiological Effects ◽  
Therapeutic Approaches ◽  
The Impact ◽  
Long Chain

Cardiovascular disease remains a leading cause of mortality worldwide. Unresolved inflammation plays a critical role in cardiovascular diseases development. Specialized Pro-Resolving Mediators (SPMs), derived from long chain polyunsaturated fatty acids (LCPUFAs), enhances the host defense, by resolving the inflammation and tissue repair. In addition, SPMs also have anti-inflammatory properties. These physiological effects depend on the availability of LCPUFAs precursors and cellular metabolic balance. Most of the studies have focused on the impact of SPMs in adult cardiovascular health and diseases. In this review, we discuss LCPUFAs metabolism, SPMs, and their potential effect on cardiovascular health and diseases primarily focusing in neonates. A better understanding of the role of these SPMs in cardiovascular health and diseases in neonates could lead to the development of novel therapeutic approaches in cardiovascular dysfunction.

Insights into the role of components of the tumor microenvironment in oral carcinoma call for new therapeutic approaches

2014 ◽  
Vol 325 (2) ◽  
pp. 58-64 ◽  
Author(s):  
Tuula Salo ◽  
Marilena Vered ◽  
Ibrahim O. Bello ◽  
Pia Nyberg ◽  
Carolina Cavalcante Bitu ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Oral Carcinoma ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches

scholarly journals The Impact of Stressful Life Events on Excessive Alcohol Consumption in the French Population: Findings from the GAZEL Cohort Study

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e87653 ◽  
Author(s):  
Sara L. Tamers ◽  
Cassandra Okechukwu ◽  
Alex A. Bohl ◽  
Alice Guéguen ◽  
Marcel Goldberg ◽  
...  
Keyword(s):  
Cohort Study ◽  
Alcohol Consumption ◽  
Life Events ◽  
Stressful Life Events ◽  
Stressful Life ◽  
French Population ◽  
Excessive Alcohol Consumption ◽  
Excessive Alcohol ◽  
The Impact

scholarly journals Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease

2022 ◽  
Vol 23 (2) ◽  
pp. 774
Author(s):  
Yoon Mee Yang ◽  
Ye Eun Cho ◽  
Seonghwan Hwang
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Pathological Features ◽  
Excessive Alcohol Consumption ◽  
Excessive Alcohol ◽  
The Relationship

Alcoholic liver disease (ALD) is characterized by the injury, inflammation, and scarring in the liver owing to excessive alcohol consumption. Currently, ALD is a leading cause for liver transplantation. Therefore, extensive studies (in vitro, in experimental ALD models and in humans) are needed to elucidate pathological features and pathogenic mechanisms underlying ALD. Notably, oxidative changes in the liver have been recognized as a signature trait of ALD. Progression of ALD is linked to the generation of highly reactive free radicals by reactions involving ethanol and its metabolites. Furthermore, hepatic oxidative stress promotes tissue injury and, in turn, stimulates inflammatory responses in the liver, forming a pathological loop that promotes the progression of ALD. Accordingly, accumulating further knowledge on the relationship between oxidative stress and inflammation may help establish a viable therapeutic approach for treating ALD.

Abstract 152: Stat4 Deficiency limits the Development and Progression of Atherosclerosis

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Paresa Taghavie-Moghadam ◽  
Matthew Butcher ◽  
Mark Kaplan ◽  
Jerry Nadler ◽  
Elena Galkina
Keyword(s):  
T Cells ◽  
B Cell ◽  
Plaque Burden ◽  
Chow Diet ◽  
Th1 Cells ◽  
Peripheral Tissues ◽  
The Impact ◽  
Deficient Mice

T helper 1 (Th1) cells constitute the majority of plaque infiltrating IFNγ+ T cells and play a pro-atherogenic role. Th1 cells are induced via IFNγ-dependent activation of T-box expressed in T cells (Tbet) and/or IL-12-dependent activation of signal transducer and activator of transcription 4 (Stat4). While the role of Tbet in atherosclerosis is established, the impact of the IL-12/Stat4-dependent pathway is not well defined. To address the role of Stat4 in atherosclerosis, we bred Stat4-deficient mice with Apolipoprotein E-deficient mice to generate Stat4-/-Apoe-/- mice. Deficiency of Stat4 resulted in approximately a 70% reduction in the plaque burden for 34 week old Stat4-/-Apoe-/- mice fed a chow diet and in 12 week old Stat4-/-Apoe-/- mice fed a western diet there was approximately a 40% reduction in plaque burden, both compared with diet matched Apoe-/- controls females (p<0.001). To assess the effect of Stat4 on Th1 and Treg cell differentiation, we performed an in vitro polarization assay. Deficiency of Stat4 reduced differentiation of IFNγ+ Th1 cells in Th1 conditions, but supported the induction of Tregs in Treg polarizing conditions, confirming the importance of Stat4 in regulating the Th1/Treg balance. In contrast to the in vitro results, we found no difference in the expression of both IFNγ and Foxp3 amongst Stat4-/-Apoe-/- and Apoe-/- lymph nodes and splenic CD4+ T cells; suggesting that additional cytokines in vivo may induce IFNγ+Th1 and inhibit Treg differentiation. Stat4 deficiency also resulted in increased splenic B cell numbers and a slight increase in B1a dependent T15/E06 mRNA expression. Stat4 is a powerful regulator of chemokine expression within peripheral tissues. Adoptively transferred Apoe-/- B cells and CD11b+ cells migrated more efficiently into Stat4-/-Apoe-/- aortas compared to Apoe-/- recipients. However, percentages of macrophages, as determined by CD11b+CD68+ were reduced within the spleens and aortas of Stat4-/-Apoe-/- mice as compared to Apoe-/- controls at steady state conditions. In conclusion, Stat4 deficiency results in reduced atherosclerosis via the modulation of B cell function and aortic leukocyte content.

scholarly journals Autophagy Function and Regulation in Kidney Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 100 ◽  
Author(s):  
Gur P. Kaushal ◽  
Kiran Chandrashekar ◽  
Luis A. Juncos ◽  
Sudhir V. Shah
Keyword(s):  
Cell Death ◽  
Renal Injury ◽  
Mammalian Target Of Rapamycin ◽  
Kidney Injury ◽  
Therapeutic Approaches ◽  
Regulated Necrosis ◽  
Atg Genes ◽  
Cellular Components ◽  
The Impact

Autophagy is a dynamic process by which intracellular damaged macromolecules and organelles are degraded and recycled for the synthesis of new cellular components. Basal autophagy in the kidney acts as a quality control system and is vital for cellular metabolic and organelle homeostasis. Under pathological conditions, autophagy facilitates cellular adaptation; however, activation of autophagy in response to renal injury may be insufficient to provide protection, especially under dysregulated conditions. Kidney-specific deletion of Atg genes in mice has consistently demonstrated worsened acute kidney injury (AKI) outcomes supporting the notion of a pro-survival role of autophagy. Recent studies have also begun to unfold the role of autophagy in progressive renal disease and subsequent fibrosis. Autophagy also influences tubular cell death in renal injury. In this review, we reported the current understanding of autophagy regulation and its role in the pathogenesis of renal injury. In particular, the classic mammalian target of rapamycin (mTOR)-dependent signaling pathway and other mTOR-independent alternative signaling pathways of autophagy regulation were described. Finally, we summarized the impact of autophagy activation on different forms of cell death, including apoptosis and regulated necrosis, associated with the pathophysiology of renal injury. Understanding the regulatory mechanisms of autophagy would identify important targets for therapeutic approaches.

scholarly journals Second hits exacerbate alcohol-related organ damage: an update

2020 ◽  
Vol 56 (1) ◽  
pp. 8-16
Author(s):  
Natalia A Osna ◽  
Murali Ganesan ◽  
Devanshi Seth ◽  
Todd A Wyatt ◽  
Srivatsan Kidambi ◽  
...  
Keyword(s):  
Liver Injury ◽  
Alcohol Exposure ◽  
Organ Damage ◽  
Lifestyle Factor ◽  
Matrix Stiffness ◽  
Reactive Aldehydes ◽  
Wide Range ◽  
Excessive Alcohol ◽  
The Impact

Abstract Chronic and excessive alcohol abuse cause direct and indirect detrimental effects on a wide range of body organs and systems and accounts for ~4% of deaths worldwide. Many factors influence the harmful effects of alcohol. This concise review presents newer insights into the role of select second hits in influencing the progression of alcohol-induced organ damage by synergistically acting to generate a more dramatic downstream biological defect. This review specifically addresses on how a lifestyle factor of high fat intake exacerbates alcoholic liver injury and its progression. This review also provides the mechanistic insights into how increasing matrix stiffness during liver injury promotes alcohol-induced fibrogenesis. It also discusses how hepatotropic viral (HCV, HBV) infections as well as HIV (which is traditionally not known to be hepatotropic), are potentiated by alcohol exposure to promote hepatotoxicity and fibrosis progression. Finally, this review highlights the impact of reactive aldehydes generated during alcohol and cigarette smoke coexposure impair innate antimicrobial defense and increased susceptibility to infections. This review was inspired by the symposium held at the 17th Congress of the European Society for Biomedical research on Alcoholism in Lille, France entitled ‘Second hits in alcohol-related organ damage’.

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