Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Current and Potential Therapies Targeting Inflammation in NASH.

ABSTRACT: Nonalcoholic steatohepatitis (NASH) is the advanced form of nonalcoholic fatty liver disease (NAFLD). It is characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. Inflammation plays a key role in the progression of NASH and can be provoked by intrahepatic (e.g., lipotoxicity, immune responses, oxidative stress and cell death) and extrahepatic sources (adipose tissue or gut). The identification of triggers of inflammation is central to understanding the mechanisms in NASH development and progression and in designing targeted therapies that can halt or reverse the disease. In this review, we summarize the current and potential therapies targeting inflammation in NASH.

SUBMITTER: Albhaisi S

PROVIDER: S-EPMC8678040 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Current and Potential Therapies Targeting Inflammation in NASH.

Albhaisi Somaya S Noureddin Mazen M

Frontiers in endocrinology 20211203

Nonalcoholic steatohepatitis (NASH) is the advanced form of nonalcoholic fatty liver disease (NAFLD). It is characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. Inflammation plays a key role in the progression of NASH and can be provoked by intrahepatic (e.g., lipotoxicity, immune responses, oxidative stress and cell death) and extrahepatic sources (adipose tissue or gut). The identification of triggers of inflammation is central to understanding the mechanisms ...[more]

PMID: 34925237

Similar Datasets

Current and future pharmacological therapies for NAFLD/NASH.

Project description:Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and there is no approved pharmacotherapy. The efficacy of vitamin E and pioglitazone has been established in nonalcoholic steatohepatitis (NASH), a progressive form of NAFLD. GLP-1RA and SGLT2 inhibitors, which are currently approved for use in diabetes, have shown early efficacy in NASH, and also have beneficial cardiovascular or renal effects. Innovative NASH therapies include four main pathways. The first approach is targeting hepatic fat accumulation. Medications in this approach include modulation of peroxisome proliferator-activator receptors (e.g., pemafibrate, elafibranor), medications targeting farnesoid X receptor axis [obeticholic acid; OCA)], inhibitors of de novo lipogenesis (aramchol, ACC inhibitor), and fibroblast growth factor-21 analogues. A second target is oxidative stress, inflammation, and apoptosis. This class of drug includes apoptosis signaling kinase 1 (ASK1) inhibitor and emricasan (an irreversible caspase inhibitor). A third target is intestinal microbiomes and metabolic endotoxemia. Several agents are in ongoing trials, including IMMe124, TLR4 antagonist, and solithromycin (macrolide antibiotics). The final target is hepatic fibrosis, which is strongly associated with all-cause or liver-related mortality in NASH. Antifibrotic agents are a cysteine-cysteine motif chemokine receptor-2/5 antagonist (cenicriviroc; CVC) and galectin 3 antagonist. Among a variety of medications in development, four agents such as OCA, elafibranor, ASK1 inhibitor, and CVC are currently being evaluated in an international phase 3 trial for the treatment of NASH. Within the next few years, the availability of therapeutic options for NASH will hopefully curb the rising trend of NASH-related diseases.

| S-EPMC5847174 | biostudies-literature

Current treatment paradigms and emerging therapies for NAFLD/NASH.

Project description:Non-alcoholic fatty liver disease (NAFLD) is one the fastest emerging manifestations of the metabolic syndrome worldwide. Non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, may culminate into cirrhosis and hepatocellular cancer (HCC) and is presently a leading cause of liver transplant. Although a steady progress is seen in understanding of the disease epidemiology, pathogenesis and identifying therapeutic targets, the slowest advancement is seen in the therapeutic field. Currently, there is no FDA approved therapy for this disease and appropriate therapeutic targets are urgently warranted. In this review we discuss the role of lifestyle intervention, pharmacological agents, surgical approaches, and gut microbiome, with regard to therapy for NASH. In particular, we focus the role of insulin sensitizers, thyroid hormone mimetics, antioxidants, cholesterol lowering drugs, incretins and cytokines as therapeutic targets for NASH. We highlight these targets aiming to optimize the future for NASH therapy.

| S-EPMC7116261 | biostudies-literature

Current and potential inflammation targeted therapies in head and neck cancer.

Project description:Inflammation often exists in the tumor microenvironment and is induced by inflammatory mediators (cytokines, chemokines, and growth factors) produced by the tumor, stroma, and infiltrating cells. These factors modulate tissue remodeling and angiogenesis and actively promote tumor cell survival and chemoresistance through autocrine and paracrine mechanisms. Head and neck squamous cell carcinomas (HNSCCs) are highly inflammatory and aggressive in nature, and they express a number of cytokines and growth factors involved in inflammation. These cytokines and growth factors activate important signal transduction pathways, including NF-kappaB, JAK/STAT, and PI3K/Akt/mTOR, which regulate the expression of genes controlling growth, survival, and chemosensitivity. This review provides an update on recent advances in the understanding of the mechanisms driving cancer-related inflammation in HNSCC and on molecular targeted therapies under preclinical and clinical investigation.

| S-EPMC2731001 | biostudies-other

Potential lymphangiogenesis therapies: Learning from current antiangiogenesis therapies-A review.

Project description:In recent years, lymphangiogenesis, the process of lymphatic vessel formation from existing lymph vessels, has been demonstrated to have a significant role in diverse pathologies, including cancer metastasis, organ graft rejection, and lymphedema. Our understanding of the mechanisms of lymphangiogenesis has advanced on the heels of studies demonstrating vascular endothelial growth factor C as a central pro-lymphangiogenic regulator and others identifying multiple lymphatic endothelial biomarkers. Despite these breakthroughs and a growing appreciation of the signaling events that govern the lymphangiogenic process, there are no FDA-approved drugs that target lymphangiogenesis. In this review, we reflect on the lessons available from the development of antiangiogenic therapies (26 FDA-approved drugs to date), review current lymphangiogenesis research including nanotechnology in therapeutic drug delivery and imaging, and discuss molecules in the lymphangiogenic pathway that are promising therapeutic targets.

| S-EPMC6135718 | biostudies-literature

Current and emerging biologic therapies targeting eosinophilic disorders.

Project description:Eosinophilic disorders include a wide array of conditions in which eosinophils play a primary pathophysiologic role. While historically treated with corticosteroids and immunosuppressants, knowledge of eosinophil biology has led to the development of several biologics targeting eosinophils. In this review, we discuss the current US Food and Drug Administration (FDA) approved eosinophil-specific biologics targeting IL-5 (mepolizumab and reslizumab) and IL-5R (benralizumab) along with biologics under investigation targeting siglec-8 (lirentelimab). We discuss efficacy and safety data from trials of these medications in conditions including eosinophilic asthma, hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), and eosinophilic gastrointestinal disease (EGID). Additionally, we discuss case reports utilizing these medications in conditions including drug reaction with eosinophilia and systemic symptoms (DRESS), allergic bronchopulmonary aspergillosis (ABPA), and eosinophilic pneumonia, among others. While eosinophilic targeting biologic therapy has been successful in eosinophilic asthma, HES, EGPA, and CRSwNP leading to FDA approval for these conditions, trials treating EoE and EGID have been disappointing to date. Given the increasing number of trials utilizing these biologics, it will be imperative for the allergist-immunologist to stay up to date on the latest treatment options to provide the most optimal care for eosinophilic disorders.

| S-EPMC9356173 | biostudies-literature

Therapies in non-alcoholic steatohepatitis (NASH).

Project description:The hallmark of non-alcoholic fatty liver disease (NAFLD) is excessive fatty accumulation in the hepatocytes, which may be an isolated event (non-alcoholic fatty liver, NAFL) or accompanied by evidence of inflammation and cell injury with or without fibrosis (non-alcoholic steatohepatitis, NASH). NASH, the more aggressive form of NAFLD, may progress to cirrhosis and hepatocellular carcinoma. Since NASH is estimated to overtake hepatitis C virus infection as the leading cause of liver transplantation in the US in the coming decade, and there are no current FDA-approved therapies for this disease, the need to find appropriate therapeutic targets is now more urgent than ever before. Diet and other lifestyle modifications have always been difficult to maintain and this approach alone has not slowed the rising tide of the disease. While the results of traditional therapies such as vitamin E and pioglitazone have been significant for steatosis and inflammation, they have had no effect on fibrosis, which is the strongest indicator of mortality in this condition. However, the understanding of the pathogenesis and progression of NASH has evolved and several promising novel therapies to target and possibly reverse fibrosis are being evaluated, making the future outlook of NASH therapy more optimistic.

| S-EPMC5492893 | biostudies-literature

Targeting inflammation in emerging therapies for genetic retinal disease.

Project description:Genetic retinal diseases such as age-related macular degeneration and monogenic diseases such as retinitis pigmentosa account for some of the commonest causes of blindness in the developed world. Diverse genetic abnormalities and environmental causes have been implicated in triggering multiple pathological mechanisms such as oxidative stress, lipofuscin deposits, neovascularisation, and programmed cell death. In recent years, inflammation has also been highlighted although whether inflammatory mediators play a central role in pathogenesis or a more minor secondary role has yet to be established. Despite this, numerous interventional studies, particularly targeting the complement system, are underway with the promise of novel therapeutic strategies for these important blinding conditions.

| S-EPMC3594980 | biostudies-literature

Treatment Candidacy for Pharmacologic Therapies for NASH.

Project description:Nonalcoholic steatohepatitis (NASH) has emerged as one of the important causes of cirrhosis and hepatocellular carcinoma, and over 50 therapeutic agents are in various phases of clinical development. Recently, obeticholic acid has achieved the interim histological endpoint of fibrosis improvement with no worsening of NASH in the phase 3 REGENERATE study, and now patients are being followed for long-term clinical outcomes. Several drugs are in Phase 3 trials with a goal to achieve conditional registration under the subpart H pathway by the United States Food and Drug Administration (FDA). It is thus timely to consider the current situation and the way ahead in the management of NASH. In this article, we review the natural history of nonalcoholic fatty liver disease, upcoming treatments for NASH and various assessments. Based on the current knowledge, we discuss what should be the target treatment population and whether noninvasive tests are ready to guide NASH treatments both for patient selection and evaluation of treatment response.

| S-EPMC8908435 | biostudies-literature

From Inflammation to Current and Alternative Therapies Involved in Wound Healing.

Project description:Wound healing is a complex event that develops in three overlapping phases: inflammatory, proliferative, and remodeling. These phases are distinct in function and histological characteristics. However, they depend on the interaction of cytokines, growth factors, chemokines, and chemical mediators from cells to perform regulatory events. In this article, we will review the pathway in the skin healing cascade, relating the major chemical inflammatory mediators, cellular and molecular, as well as demonstrating the local and systemic factors that interfere in healing and disorders associated with tissue repair deficiency. Finally, we will discuss the current therapeutic interventions in the wounds treatment, and the alternative therapies used as promising results in the development of new products with healing potential.

| S-EPMC5547704 | biostudies-other

Potential therapies targeting nuclear metabolic regulation in cancer.

Project description:The interplay between genetic alterations and metabolic dysregulation is increasingly recognized as a pivotal axis in cancer pathogenesis. Both elements are mutually reinforcing, thereby expediting the ontogeny and progression of malignant neoplasms. Intriguingly, recent findings have highlighted the translocation of metabolites and metabolic enzymes from the cytoplasm into the nuclear compartment, where they appear to be intimately associated with tumor cell proliferation. Despite these advancements, significant gaps persist in our understanding of their specific roles within the nuclear milieu, their modulatory effects on gene transcription and cellular proliferation, and the intricacies of their coordination with the genomic landscape. In this comprehensive review, we endeavor to elucidate the regulatory landscape of metabolic signaling within the nuclear domain, namely nuclear metabolic signaling involving metabolites and metabolic enzymes. We explore the roles and molecular mechanisms through which metabolic flux and enzymatic activity impact critical nuclear processes, including epigenetic modulation, DNA damage repair, and gene expression regulation. In conclusion, we underscore the paramount significance of nuclear metabolic signaling in cancer biology and enumerate potential therapeutic targets, associated pharmacological interventions, and implications for clinical applications. Importantly, these emergent findings not only augment our conceptual understanding of tumoral metabolism but also herald the potential for innovative therapeutic paradigms targeting the metabolism-genome transcriptional axis.

| S-EPMC10685089 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data