Interleukin-6 in Hepatocellular Carcinoma: A Dualistic Point of View

Biomedicines, Год журнала: 2023, Номер 11(10), С. 2623 - 2623

Опубликована: Сен. 24, 2023

Hepatocellular Carcinoma (HCC) is a pressing health concern, demanding deep understanding of various mediators’ roles in its development for therapeutic progress. Notably, interleukin-6 (IL-6) has taken center stage investigations due to intricate and context-dependent functions. This review delves into the dual nature IL-6 HCC, exploring seemingly contradictory as both promoter an inhibitor disease progression. We dissect pro-tumorigenic effects IL-6, including impact on tumor growth, angiogenesis, metastasis. Concurrently, we examine anti-tumorigenic attributes, such role immune response activation, cellular senescence induction, surveillance. Through comprehensive exploration interactions between microenvironment, this highlights need nuanced comprehension signaling HCC. It underscores importance tailored strategies that consider dynamic stages diverse surroundings within microenvironment. Future research directions aimed at unraveling multifaceted mechanisms HCC hold promise developing more effective treatment improving patient outcomes.

Язык: Английский

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Signaling pathways of liver regeneration: Biological mechanisms and implications

iScience, Год журнала: 2023, Номер 27(1), С. 108683 - 108683

Опубликована: Дек. 7, 2023

SummaryThe liver possesses a unique regenerative ability to restore its original mass, in this regard, partial hepatectomy (PHx) and transplantation (PLTx) can be executed smoothly safely, which has important implications for the treatment of disease. Liver regeneration (LR) very complicated procedure that involves multiple cytokines transcription factors interact with each other activate different signaling pathways. Activation these pathways drive LR process, divided into three stages, namely, initiation, progression, termination stages. Therefore, it is investigate involved elucidate mechanism LR. This study reviews latest research on key stages LR.Graphical abstract

Язык: Английский

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Cell therapy in end-stage liver disease: replace and remodel

Stem Cell Research & Therapy, Год журнала: 2023, Номер 14(1)

Опубликована: Май 25, 2023

Abstract Liver disease is prevalent worldwide. When it reaches the end stage, mortality rises to 50% or more. Although liver transplantation has emerged as most efficient treatment for end-stage disease, its application been limited by scarcity of donor livers. The lack acceptable organs implies that patients are at high risk while waiting suitable In this scenario, cell therapy a promising approach. Most time, transplanted cells can replace host hepatocytes and remodel hepatic microenvironment. For instance, derived from livers stem colonize proliferate in liver, hepatocytes, restore function. Other cellular candidates, such macrophages mesenchymal cells, microenvironment, thereby repairing damaged liver. recent years, transitioned animal research early human studies. review, we will discuss treatment, especially focusing on various types utilized transplantation, elucidate processes involved. Furthermore, also summarize practical obstacles offer potential solutions.

Язык: Английский

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Targeting MET in Non-Small Cell Lung Cancer (NSCLC): A New Old Story?

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(12), С. 10119 - 10119

Опубликована: Июнь 14, 2023

In recent years, we have seen the development and approval for clinical use of an increasing number therapeutic agents against actionable oncogenic drivers in metastatic non-small cell lung cancer (NSCLC). Among them, selective inhibitors, including tyrosine kinase inhibitors (TKIs) monoclonal antibodies targeting mesenchymal-epithelial transition (MET) receptor, been studied patients with advanced NSCLC MET deregulation, primarily due to exon 14 skipping mutations or amplification. Some TKIs, capmatinib tepotinib, proven be highly effective this molecularly defined subgroup are already approved use. Other similar being tested early-stage trials promising antitumor activity. The purpose review is provide overview signaling pathways, alterations focusing on mutations, laboratory techniques used detect alterations. Furthermore, will summarize currently available data ongoing studies as well mechanisms resistance TKIs new potential strategies, combinatorial approaches, improve outcomes 14-altered patients.

Язык: Английский

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Heterogeneity of hepatocyte dynamics restores liver architecture after chemical, physical or viral damage

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 10, 2024

Abstract Midlobular hepatocytes are proposed to be the most plastic hepatic cell, providing a reservoir for hepatocyte proliferation during homeostasis and regeneration. However, other mechanisms beyond hyperplasia have been little explored contribution of subpopulations regeneration has controversial. Thus, re-examining dynamics is critical cell therapy treatment liver diseases. Using mouse model hepatocyte- non-hepatocyte- multicolor lineage tracing, we demonstrate that midlobular also undergo hypertrophy in response chemical, physical, viral insults. Our study shows this subpopulation combats impairment after infection with coronavirus. Furthermore, pericentral expand number size repair process Galectin-9-CD44 pathway may driving these processes. Notably, identified transdifferentiation fusion severe injury contribute recover function.

Язык: Английский

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Adipose-Derived Stem Cells (ADSCs) Supplemented with Hepatocyte Growth Factor (HGF) Attenuate Hepatic Stellate Cell Activation and Liver Fibrosis by Inhibiting the TGF-β/Smad Signaling Pathway in Chemical-Induced Liver Fibrosis Associated with Diabetes

Cells, Год журнала: 2022, Номер 11(21), С. 3338 - 3338

Опубликована: Окт. 22, 2022

Liver fibrosis can develop on the background of hyperglycemia in diabetes mellitus. However, xenobiotic-related factors may accelerate diabetes-associated liver fibrosis. In this study, we aimed to assess antfibrotic effect ADSC and HGF therapy establish cellular molecular mechanisms through vitro vivo experiments. vitro, TGF-β1-activated hepatic stellate cells (HSCs) were cocultured with ADSCs or HGF, expression several markers was investigated. The antifibrotic ADSCs, supplemented further assessed diabetic mice experimentally induced. results showed inhibition HSC proliferation decrease fibrogenesis markers. Coadministration enhanced effects confirmed by downregulation Col I, α-SMA, TGF-β1, Smad2, while Smad7 upregulated. Moreover, stem cell considerably attenuated inflammation microvesicular steatosis, decreased collagen deposits, alleviated conclusion, HGF-based might be interest for treatment patients, consecutive aggression exerts different environmental factors.

Язык: Английский

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New therapeutic concepts against ischemia-reperfusion injury in organ transplantation

Expert Review of Clinical Immunology, Год журнала: 2023, Номер 19(10), С. 1205 - 1224

Опубликована: Июль 25, 2023

Ischemia-reperfusion injury (IRI) involves a positive amplification feedback loop that stimulates innate immune-driven tissue damage associated with organ procurement from deceased donors and during transplantation surgery. As our appreciation of its basic immune mechanisms has improved in recent years, translating putative biomarkers into therapeutic interventions clinical remains challenging.

Язык: Английский

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New and Old Key Players in Liver Cancer

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(24), С. 17152 - 17152

Опубликована: Дек. 5, 2023

Liver cancer represents a major health problem worldwide with growing incidence and high mortality, hepatocellular carcinoma (HCC) being the most frequent. Hepatocytes are likely cellular origin of HCCs through accumulation genetic alterations, although hepatic progenitor cells (HPCs) might also be candidates in specific cases, as discussed here. HCC usually develops context chronic inflammation, fibrosis, cirrhosis, role fibrosis is controversial. The interplay between hepatocytes, immune stellate key issue. This review summarizes critical aspects liver tumor microenvironment paying special attention to platelets new players, which exert both pro- anti-tumor effects, determined by contexts tight regulation platelet signaling. Additionally, relevance signaling pathways, mainly HGF/MET, EGFR TGF-β discussed. HGF produced different regulate not only cell fate but HPCs, inflammation these players processes. C3G/RAPGEF1, required for proper function HGF/MET highlighted, due its ability promote growth and, HPC platelet-mediated actions on cancer.

Язык: Английский

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A perspective on emerging therapies in metastatic colorectal cancer: Focusing on molecular medicine and drug resistance

Cell Biochemistry and Function, Год журнала: 2024, Номер 42(1)

Опубликована: Янв. 1, 2024

Abstract The majority of cancer cases are colorectal cancer, which is also the second largest cause cancer‐related deaths worldwide. Metastasis leading death for patients with cancer. Metastatic incidence on rise due to a tiny percentage tumors developing resistant medicines despite advances in treatment tactics. Cutting‐edge targeted medications now go‐to option customized and all‐encompassing CRC care. Specifically, multitarget kinase inhibitors, antivascular endothelial growth factors, epidermal factor receptors widely used clinical practice CRC‐targeted treatments. Rare targets metastatic becoming more well‐known developments precision diagnostics extensive use second‐generation sequencing technology. These include KRAS mutation, BRAF V600E HER2 overexpression/amplification, MSI‐H/dMMR. Incorporating certain into trials has significantly increased patient survival rates, opening new avenues bringing fresh viewpoints treating focused therapies change how treated, giving hope better results. markers can transform individualize therapy regimens. They could open door precisely effective medicines, improving outcomes quality life. fast‐growing body knowledge regarding molecular biology latest gene directly responsible this advancement.

Язык: Английский

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Fucoxanthin Enhances the Antifibrotic Potential of Placenta-derived Mesenchymal Stem Cells in a CCl4-induced Mouse Model of Liver

Current Stem Cell Research & Therapy, Год журнала: 2024, Номер 19(11), С. 1484 - 1496

Опубликована: Янв. 11, 2024

The effectiveness of fucoxanthin (Fx) in liver diseases has been reported due to its anti-inflammatory and antifibrotic effects. Mesenchymal stem cells (MSCs)-based therapy also proposed as a promising strategy for fibrosis treatment. Recent studies have shown that the co-administration MSCs drugs demonstrates pronounced effect on fibrosis.

Язык: Английский

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