An IFNγ-dependent immune-endocrine circuit lowers blood glucose to potentiate the innate anti-viral immune response DOI Creative Commons
Bojan Polić, Marko Šestan, Ante Benić

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 5, 2024

Abstract Viral infection makes us feel sick. The extent of these changes to our metabolism are relative the severity disease. Whether blood glucose levels subject infection-induced modulation is largely unknown. Here we show that strong, non-lethal restricts systemic availability which promotes antiviral IFN-I response. Following viral mice, find IFNγ produced by γδ T cells directly stimulates pancreatic β-cells increase glucose-induced insulin release. Subsequently, hyperinsulinemia lessens endogenous output liver. Glucose restriction enhances type-I interferon production curtailing lactate-mediated inhibition IRF3 and NF-κB signaling. Induced hyperglycemia constrained increased mortality upon infection. Our findings identify as a physiological mechanism bring body into heightened state responsiveness pathogens. This immune-endocrine circuit disrupted in hyperglycemia, explains why people with metabolic disease more susceptible

Language: Английский

Comprehensive review and updated analysis of DNA methylation in hepatocellular carcinoma: From basic research to clinical application DOI Creative Commons
Lin Su, Jiawen Bu, Jiahui Yu

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(11)

Published: Oct. 27, 2024

Abstract Hepatocellular carcinoma (HCC) is a primary malignant tumour, ranking second in global mortality rates and posing significant health threats. Epigenetic alterations, particularly DNA methylation, have emerged as pivotal factors associated with HCC diagnosis, therapy, prognosis progression. However, comprehensive analysis of the methylation mechanism driving progression its potential therapeutic biomarker remains lacking. This review attempts to comprehensively summarise various aspects such mechanism, detection methods biomarkers aiding treatment prognostic assessment HCC. It also explores role regulating HCC's sorafenib resistance, alongside elaborating effects methyltransferase inhibitors on A detailed examination these underscores research tumour cells elucidate mechanisms, identify diagnostic markers develop new tumour‐specific for Key points summary diagnosis treatment. The hepatocellular carcinoma's inhibitors. Deep critical discovering novel

Language: Английский

Citations

3
Inflammation in Steatotic Liver Diseases: Pathogenesis and Therapeutic Targets DOI

Shengying Qian,

Xiaolin Wang,

Yingfen Chen

et al.

Seminars in Liver Disease, Journal Year: 2024, Volume and Issue: unknown

Published: June 5, 2024

Alcohol-related liver disease (ALD) and metabolic dysfunction-associated steatotic (MASLD), two main types of (SLDs), are characterized by a wide spectrum several different disorders, including simple steatosis, steatohepatitis, cirrhosis, hepatocellular carcinoma. Multiple immune cell-mediated inflammatory responses not only orchestrate the killing removal infected/damaged cells but also exacerbate development SLDs when excessive or persistent inflammation occurs. In recent years, single-cell spatial transcriptome analyses have revealed heterogeneity liver-infiltrated in ALD MASLD, revealing new immunopathological picture SLDs. this review, we will emphasize roles key pathogenesis MASLD discuss inflammation-based approaches for effective SLD intervention. conclusion, study immunological mechanisms, especially highly specific cell population functions, may provide novel therapeutic opportunities life-threatening disease.

Language: Английский

Citations

2
The immune microenvironment of steatotic hepatocellular carcinoma: Current findings and future prospects DOI Creative Commons
Jacinth Wing‐Sum Cheu, Carmen Chak‐Lui Wong

Hepatology Communications, Journal Year: 2024, Volume and Issue: 8(9)

Published: Sept. 1, 2024

Hepatocellular carcinoma (HCC), the major type of primary liver cancer, is notorious for its resistance to systemic treatments. The field has made a great leap in past decade, with number FDA-approved therapies advanced HCC increasing from 1 9. Although tyrosine kinase inhibitors remain most common first-line option as monotherapy treatment, clinical success immune checkpoint inhibitors, especially when used combination anti-VEGF/VEGFR will likely transform treatment landscape. While represent an exciting therapeutic revenue HCC, recent studies have revealed that nonviral which primarily caused by metabolic dysfunction-associated steatotic hepatitis (MASH), distinct and less favorable response inhibitors. MASH rapidly etiology HCC. microenvironment MASH-HCC greatly affected intertwined pathological processes steatosis-induced iterative cycles between steatohepatitis injury. Here, we present timely summary MASH-HCC. We delve into use cutting-edge technologies, such single-cell RNA sequencing, spatial transcriptomics, mass cytometry imaging, deconvolute complexity ecosystem also discuss novel innovations preclinical models, inhibitor, epigenetic immunomodulator. These all ability subvert MASH-HCC, improving efficiency anti-PD-1. awaiting new drugs be tested trials, knowledge gained these investigations crucial development personalized effective strategies

Language: Английский

Citations

2
Immune system dysregulation in the pathogenesis of non-alcoholic steatohepatitis: unveiling the critical role of T and B lymphocytes DOI Creative Commons
Merve Çebi, Yusuf Yılmaz

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 1, 2024

Non-alcoholic fatty liver disease (NAFLD), characterized by the excessive accumulation of fat within cytoplasm hepatocytes (exceeding 5% weight) in individuals without significant alcohol consumption, has rapidly evolved into a pressing global health issue, affecting approximately 25% world population. This condition, closely associated with obesity, type 2 diabetes, and metabolic syndrome, encompasses spectrum disorders ranging from simple steatosis inflammation to non-alcoholic steatohepatitis (NASH) cirrhotic disease. Recent research illuminated complex interplay between immune responses pathogenesis NASH, underscoring critical role played T B lymphocytes. These cells not only contribute necroinflammatory changes hepatic lobules but may also drive onset progression fibrosis. narrative review aims provide comprehensive exploration effector mechanisms employed cells, their respective subpopulations NASH. Understanding immunological complexity NASH holds profound implications for development targeted immunotherapeutic strategies combat this increasingly prevalent burdensome

Language: Английский

Citations

1
An IFNγ-dependent immune-endocrine circuit lowers blood glucose to potentiate the innate anti-viral immune response DOI Creative Commons
Bojan Polić, Marko Šestan, Ante Benić

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 5, 2024

Abstract Viral infection makes us feel sick. The extent of these changes to our metabolism are relative the severity disease. Whether blood glucose levels subject infection-induced modulation is largely unknown. Here we show that strong, non-lethal restricts systemic availability which promotes antiviral IFN-I response. Following viral mice, find IFNγ produced by γδ T cells directly stimulates pancreatic β-cells increase glucose-induced insulin release. Subsequently, hyperinsulinemia lessens endogenous output liver. Glucose restriction enhances type-I interferon production curtailing lactate-mediated inhibition IRF3 and NF-κB signaling. Induced hyperglycemia constrained increased mortality upon infection. Our findings identify as a physiological mechanism bring body into heightened state responsiveness pathogens. This immune-endocrine circuit disrupted in hyperglycemia, explains why people with metabolic disease more susceptible

Language: Английский

Citations

0