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Advances in Nanonutraceuticals: Indian Scenario
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Amthul Azeez, Mubeen Sultana, Lucky, Noorjahan
Persistent inflammation, following liver damage, often results in the formation of fibrous tissue. Therefore, often, any medication which is given to reduce the inflammation ideally has an anti-fibrotic effect. The sequence of steps, which lead to fibrosis are outlined as oxidative stress caused by the generation of ROS followed by scar formation, leading to a reduced inflammatory response. This inflammation causes the crippling of hepatic stellate cell (HSC) activation causing fibrogenesis as seen in cirrhosis of the liver. In this context, it can be said, that certain natural compounds or Unani preparations which are identified as antioxidants, can be given as a therapy to reduce the ROS and in a way to prevent fibrosis of hepatic tissue. The effectiveness of this treatment depends upon the agility of the antioxidant reaching the target site i.e., liver (Kawada et al. 1998).
The liver, gallbladder and pancreas
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Dina G. Tiniakos, Alastair D. Burt
Despite the many diverse causes of liver disease, the liver has a rather limited set of responses to injury. In some conditions, the injury is manifest by the accumulation of lipids within the hepatocytes: this is a central theme in alcohol-related liver disease and in liver injury associated with the so-called ‘metabolic syndrome’ (type 2 diabetes, hypertension, obesity, and dyslipidaemia) – the fatty liver disease. In many disorders, there is irreversible liver cell injury through either necrosis or apoptosis (see Chapter 3). Inflammation is a common feature, particularly in chronic conditions. The predominant inflammatory cell type is the T lymphocyte; these cells may have a key role in liver cell apoptosis. In response to liver cell loss, there is regeneration of surviving epithelial cells as noted above. In some situations, there may be massive liver cell necrosis, where most of the parenchyma is lost; under such circumstances, there may then not be sufficient critical mass of surviving cells to repopulate the liver. When there is persistent injury and inflammation there is stimulation of a repair process involving the hepatic stellate cells; this leads to the development of fibrosis and is discussed more fully in Chapter 3.
Turning Blood into Liver
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Bryon E. Petersen, Neil D. Theise
Evarts et al (1987 and 1989), show that the oval cell compartment is activated extensively in a 2-Acetylaminoflourene/two thirds partial-hepatectomy (2-AAF/PHx) model. This model is a variation of the Solt-Farber protocol and has become the trade benchmark.22,23Figure 1 represents a generic timeline for this model of liver regeneration from oval “stem” cells. These conditions markedly suppress mature hepatocyte proliferation and, when followed by partial hepatectomy activate, oval cell proliferation. Further studies, presented by the same investigators, showed that proliferation of the oval cells are associated with the activation of the hepatic stellate cells, which may regulate the developmental fate of the progenitor cells either directly, by secreting growth factors such as hepatocyte growth factor (HGF), transforming growth factor-alpha (TGF-α) and TGF-β, or indirectly, through the effects of stellate cell produced extra-cellular matrix components that can also be induced by TGF-β.24 It has been shown that progenitor cell proliferation and differentiation could also be regulated by autocrine production of TGF-α, acid fibroblast growth factor (aFGF) and IGF-II (insulin-like growth factor II), since it has been shown that oval cells can make all of these factors.7
Schisandrin B promotes senescence of activated hepatic stellate cell via NCOA4-mediated ferritinophagy
Published in Pharmaceutical Biology, 2023
Mingyue Ma, Na Wei, Jieren Yang, Tingting Ding, Anping Song, Lerong Chen, Shuguo Zheng, Huanhuan Jin
Hepatic fibrosis, a reversible wound-healing response triggered by a chronic liver injury, will eventually progress to liver cirrhosis, hepatocellular carcinoma and even liver failure if not treated properly (Schuppan and Kim 2013; Pellicoro et al. 2014; Forouzanfar et al. 2016). Hepatic fibrosis is mainly characterized by excessive deposition of extrahepatic matrix proteins and activation of hepatic stellate cells (HSCs). It is well known that activated HSCs are the principal cell type in the progression of liver fibrogenesis (Bataller and Brenner 2005) and intervention in the activation of HSCs has become an effective treatment measure. There have been a number of efforts to explore effective measures to control HSCs activation, including inhibiting HSCs proliferation, promoting HSCs apoptosis, autophagy or immune clearance (Zhang et al. 2014; Tsuchida and Friedman 2017). Recent studies revealed that induction of activated HSCs senescence was also an effective strategy for blocking the process of hepatic fibrosis (Krizhanovsky et al. 2008; Zhang et al. 2021). Cellular senescence, a response to different stresses, is a highly stable cell cycle arrest (Munoz-Espin and Serrano 2014), during which cells undergo some morphological, biochemical and functional changes including increased senescence-associated β-galactosidase (SA-β-gal) activity, DNA damage and the dysfunction of telomere and telomerase system (Bernadotte et al. 2016; Herranz and Gil 2018; Shmulevich and Shmulevic 2021).
Time-dependent effect of REV-ERBα agonist SR9009 on nonalcoholic steatohepatitis and gut microbiota in mice
Published in Chronobiology International, 2023
Yinhua Ni, Sujie Nan, Liujie Zheng, Liqian Zhang, Yufeng Zhao, Zhengwei Fu
The effects of REV-ERBα activation on hepatic inflammation and fibrosis in NASH were next evaluated. F4/80 staining, as a marker of hepatic macrophage, indicated that SR9009 attenuated CL diet-induced liver macrophage activation at both time points (Figure 3a,b). qPCR analysis of pro-inflammatory cytokines expression, including interleukin 1β (Il1β), Il6, and tumor necrosis factor α (Tnfα), in the liver of NASH mice found that SR9009 treatment at ZT0 significantly downregulated the expression of all these markers, while no significant difference was found when treated at ZT12 (Figure 3c). On the other hand, Sirus red and α smooth muscle actin (α-SMA) staining revealed that clear liver fibrosis and the activation of hepatic stellate cells in the liver of NASH mice, which was ameliorated by SR9009 (Figure 3a,b). Similarly, the mRNA expression of the fibrogenic genes, such as transforming growth factor β (Tgf-β) and α-Sma, was also downregulated by SR9009 at both time points (Figure 3d).
Nonalcoholic steatohepatitis (NASH) cirrhosis: a snapshot of therapeutic agents in clinical development and the optimal design for clinical trials
Published in Expert Opinion on Investigational Drugs, 2022
Pankaj Aggarwal, Mazen Noureddin, Stephen Harrison, Sophie Jeannin, Naim Alkhouri
We envision a future where patients with NASH cirrhosis can be accurately identified without the need for invasive liver biopsy based on NITs. The same NITs will be used as surrogate efficacy endpoints that predict the future development of MALO. Establishing the threshold for change in NITs that corresponds with clinical outcomes is urgently needed before further implementation. We anticipate that the next 5 years will witness a revolution in the way we manage our patients with cirrhotic NASH. New methods to more accurately measure portal pressure are being developed including endoscopic ultrasound and spleen stiffness. New discoveries on the roles of different subsets of hepatic stellate cells in disease progression are likely to translate into relevant therapeutic interventions. Furthermore, RNA interference through antisense oligonucleotides and short interfering RNAs is a novel method to alter the expression of several genetic variants that play significant roles in the development and progression of NAFLD such as DGAT2, PNPLA3, and HSD17β13. The promise of precision medicine is finally becoming a reality as these highly selective therapeutics are being developed at a rapid pace.