Biological Perspectives of Cytokine and Hormone Networks
Andrzej Mackiewicz, Irving Kushner, Heinz Baumann in Acute Phase Proteins, 2020
Liver regeneration is a highly complex process triggered by hepatocyte growth factors (HGFs) which also appear to be potent mitogens for some epidermal and epithelial cells, but which inhibit proliferation of hepatomas (for references, see References 100 and 101). We observed that human recombinant HGF stimulates the synthesis of α2-macroglobulin in primary cultures of rat hepatocytes.102 Its effects on the synthesis of AP proteins are broader in Hep G2 cells, where HGF inhibits the synthesis of albumin, but increases the basal production of fibrinogen, α1-antichymotrypsin, and α1-proteinase inhibitor (Figure 3). However, in cells stimulated by high concentrations of IL-6, HGF decreases the maximum response of haptoglobin, fibrinogen, and α1-antichymotrypsin. A similar phenomenon was observed with insulin (Figure 3). On the other hand, TGFβ increased the production of α1 antichymotrypsin and al-proteinase inhibitor in Hep G2 cells, even at high concentrations of IL-6. These results emphasize again the existence of intricate networks of cytokines and cellular growth factors in the regulation of the liver AP response.
Fetal Growth Factors*
Emilio Herrera, Robert H. Knopp in Perinatal Biochemistry, 2020
Much of our current knowledge of the regulation of liver growth can be traced to in vivo studies on liver regeneration following partial hepatectomy in the rat. Partial hepatectomy leads to an initial alteration in hepatocytes from a quiescent to an actively replicating phenotype, resulting in restoration of liver mass.5,6 This is followed by differentiation and restoration of normal architecture and function. The events following partial hepatectomy have been used to identify growth factors and proto-oncogenes involved in regulation of liver growth, such as the transforming growth factors, TGF-α7 and TGF-β.8 Possible parallels between liver regeneration and fetal hepatic growth have influenced our recent studies (e.g., those on the ontogeny of TGF receptors).9
Genomic Instability During Aging of Postmitotic Mammalian Cells
Alvaro Macieira-Coelho in Molecular Basis of Aging, 2017
The senescence-accelerated mouse (SAM) was developed as a murine model of aging.95 The senescence-prone (SAM-P) strains, derived from AKR/J mice, were founded by repeated selection of less robust littermates. The SAM-P mice are characterized by a shorter life span and an advancement in time of the senescent phenotype, including age-related pathologies. In contrast with the genetic studies of Curtis et al.,94 senescence-prone mice show an enhanced rate of chromosomal instability over senescent-resistant (SAM-R) strains of mice derived from normal littermates of the same parental strain.96 The rate of increase of chromosomal aberration frequency in bone marrow cells paralleled the advancement of senescence in both strains, and is approximately proportional to the aging rate of the animal. In old SAM-P mice, the percentage of bone marrow cells having chromosome aberrations was nearly twice that observed for age-matched SAM-R mice. However, the average number of aberrations per cell was roughly three- to four-fold higher in SAM-P mice.96 The qualitative aspects of this study are consistent with the results from liver regeneration studies,81–86 whereas the quantitative aspects of the work are more in agreement with the data on proliferating cells in vivo.93 Direct analogy to the genetic studies cited above94 cannot be made because the SAM mice have a single genetic background in contrast to Fl hybrids produced by crosses of two inbred strains.
Prometheus Unbound: The Allure of Hepatic Regeneration
Published in Journal of Investigative Surgery, 2022
The importance of this paper is multifaceted. First, it provides important data in a patient population (with its attendant complexity) thus making the critical “jump” from the standard animal models of liver regeneration. Moreover, with the identification of the key role of HO-1, it provides us with an important piece of the liver regeneration puzzle, which remains a mystery in several respects since first observed and described in Ancient Greece [2]. However, this should not come as a surprise, given the fact that this, as most processes in nature, is actually quite an intricate one, involving several different molecules and multiple types of cells, with subpopulations of their own, all of which have to eventually “communicate” in a manner that will reestablish the various, complicated hepatic functions [3]. Finally, this paper demonstrates the relationship between liver regeneration and liver dysfunction, which allows the possibility of being able to (a) predict and (b) influence post-operative liver dysfunction, thus transforming hepatic surgery to a safer procedure and, potentially, allowing for improved patient selection.
Flavonoid constituents and protective efficacy of Citrus reticulate (Blanco) leaves ethanolic extract on thioacetamide-induced liver injury rats
Published in Biomarkers, 2023
Usama W. Hawas, Mohamed A. El-Ansari, Abeer F. Osman, Asmaa F. Galal, Lamia T. Abou El-Kassem
The liver is a critical organ in the human body that is responsible for the regulation of several metabolic functions and physiological processes. Its ability to detoxify xenobiotics makes it especially crucial for maintaining bodily health. Several mechanisms have been proposed to explain the hepatotoxicity of viral or non-viral hepatitis. In both cases, the cornerstone mechanisms are inflammation and oxidative stress-induced membrane lipid peroxidation (Tarocchi et al.2014). In addition, the liver’s self-healing and regenerative capacity can lead to excessive accumulation of extracellular matrix (ECM) proteins such as collagen, followed by progressive tissue scarring, cirrhosis, and loss of liver function. Despite advancements in contemporary medicine, there is no effective treatment strategy for enhancing liver regeneration, protecting the liver, or stimulating hepatic function (Madrigal-Santillán et al. 2014). Current drugs, such as pegylated interferon-alpha (IFN-α) and ribavirin, used to treat hepatitis virus infection, are not always successful in curing patients, and some of them may not tolerate this treatment. Similar restrictions have been found with silymarin, the most well-known hepatoprotective compound, when used to treat chronic liver damage such as cirrhosis. Thus, it is necessary to identify highly effective drugs for the treatment of liver diseases, emphasising their low toxicity.
Perioperative Enteral Nutrition Improves Postoperative Recovery for Patients with Primary Liver Cancer: A Randomized Controlled Clinical Trial
Published in Nutrition and Cancer, 2021
Xiaopeng Yan, Lianxin Liu, Yamin Zhang, Tianqiang Song, Yingjian Liang, Zirong Liu, Xu Bao, Liang Mao, Yudong Qiu
Primary liver cancer is one of the most prevalent life-threating diseases in China, and liver resection is the major therapy for this malignancy (1). Recently, various methods have been advocated perioperatively to maintain liver function and promote liver regeneration after liver resections. These include systemic interventions such as antibiotics in perioperative period and methods to improve general health and the immunity of the individual such as prebiotics and probiotics (2–4). Among them, nutritional support is also a vital approach to protect liver function. It has been demonstrated that a good preoperative nutritional status could reduce the postoperative morbidity or mortality and consequently the costs of care after surgery (5). Moreover, malnutrition is frequent in patients suffering from malignant liver disease (6–8). Optimization of nutritional status may improve hepatic function, and preoperative nutritional status is one of the key points for success of liver resection (9, 10). Enteral nutrition was suggested by the ESPEN as the first choice for liver cancer patients and should be initiated within 12–24 h postoperatively to reduce infection rate. Whole protein formulae and concentrated high-energy formulae are generally recommended as enteral nutrition for patients following liver resection (11, 12).
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