scholarly journals Pathophysiological Significance of Hepatic Apoptosis

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Kewei Wang ◽  
Bingliang Lin

Apoptosis is a classical pathological feature in liver diseases caused by various etiological factors such as drugs, viruses, alcohol, and cholestasis. Hepatic apoptosis and its deleterious effects exacerbate liver function as well as involvement in fibrosis/cirrhosis and carcinogenesis. An imbalance between apoptotic and antiapoptotic capabilities is a prominent characteristic of liver injury. The regulation of apoptosis and antiapoptosis can be a pivotal step in the treatment of liver diseases.

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 896
Author(s):  
Chun-Seok Cho ◽  
Allison Ho Kowalsky ◽  
Jun Hee Lee

The mammalian target of rapamycin complex 1 (mTORC1) is a central regulator of metabolism that integrates environmental inputs, including nutrients, growth factors, and stress signals. mTORC1 activation upregulates anabolism of diverse macromolecules, such as proteins, lipids, and nucleic acids, while downregulating autolysosomal catabolism. mTORC1 dysregulation is often found in various diseases, including cancer, cardiovascular and neurodegenerative diseases, as well as metabolic syndromes involving obesity and type II diabetes. As an essential metabolic organ, the liver requires proper regulation of mTORC1 for maintaining homeostasis and preventing pathologies. For instance, aberrant hyper- or hypoactivation of mTORC1 disrupts hepatocellular homeostasis and damages the structural and functional integrity of the tissue, leading to prominent liver injury and the development of hepatocellular carcinogenesis. Proper regulation of mTORC1 during liver diseases may be beneficial for restoring liver function and ameliorating the detrimental consequences of liver failure.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xiaoyong Xue ◽  
Jianzhi Wu ◽  
Mingning Ding ◽  
Feng Gao ◽  
Fei Zhou ◽  
...  

Abstract Background Fibrotic liver injury is a progressive scarring event, which may permanently affect liver function and progress into devastating end-stage liver diseases due to the absence of effective therapies. Si-Wu-Tang (SWT), a traditional Chinese medicine formula used in clinic to treat gynecological disorders for centuries, has been investigated in recent preliminary findings for its role in alleviating chronic liver diseases. Here we aim to elucidate the therapeutic effects and possible mechanisms of SWT against fibrotic liver injury. Methods UHPLC-MS/MS was performed to investigate the chemical characterization of SWT. After intragastrically administered with carbon tetrachloride (CCl4) every 3 days for 1-week, C57BL/6 mice were orally administered with SWT (5.2, 10.4 and 20.8 g/kg) once daily for 3 weeks along with CCl4 challenge. Liver function was determined by the measurement of serum biomarkers, hematoxylin and eosin (H&E) and Masson’s trichrome staining. Intestinal inflammatory infiltration and the disruption of intestinal barrier were examined by H&E and E-cadherin immunohistochemical staining. The microbial composition of intestinal content was determined by 16S rRNA sequencing. Serum bile acids (BAs) profiling was analyzed by LC–MS/MS. Simultaneously, the expression of genes of interest was determined by qPCR and western blot. Results SWT exhibited remarkable therapeutic effects on CCl4-induced liver fibrosis, as indicated by improved collagen accumulation in livers, intestinal barrier injury and hepatic and intestinal inflammatory response. Results of 16S rRNA sequencing revealed that SWT treatment strikingly restructured intestinal microbiota in fibrotic mice by increasing the relative abundances of Bacteroides and Lachnoclostridium and decreasing the relative abundances of Alistipes and Rikenellaceae. UHPLC-MS/MS data suggested that SWT altered the composition of BAs in circulation as evidenced by increased unconjugated BAs like cholic acid and chenodeoxycholic acid but decreased conjugated BAs including taurocholic acid and taurodeoxycholic acid, compared to that in CCl4 mice. Notably, SWT efficiently improved the imbalance of BA homeostasis in livers caused by CCl4 via activating farnesoid X receptor (FXR)-fibroblast growth factor 15 enterohepatic and FXR-small heterodimer partner hepatic pathways. Conclusion SWT decreased inflammatory response, reconstructed gut microbiota-mediated BA homeostasis as well as activated FXR pathways, which eventually protected against CCl4-induced fibrotic liver injury.


2021 ◽  
Author(s):  
Xinling Song ◽  
Wenxue Sun ◽  
Wenxin Cai ◽  
Le Jia ◽  
Jianjun Zhang

A polysaccharide named as PFP-1 was isolated from Pleurotus geesteranus fruiting body, and the potential investigations on ameliorating oxidative stress and liver injury against alcoholic liver disease (ALD) were processed...


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ewa Wunsch ◽  
Marcin Krawczyk ◽  
Malgorzata Milkiewicz ◽  
Jocelyn Trottier ◽  
Olivier Barbier ◽  
...  

Nanoscale ◽  
2020 ◽  
Author(s):  
Naishun Liao ◽  
Da Zhang ◽  
Ming Wu ◽  
Huang-Hao Yang ◽  
Xiaolong Liu ◽  
...  

Adipose tissue derived mesenchymal stem cell (ADSC)-based therapy is attractive for liver diseases, but the long-term therapeutic outcome is still far from satisfaction due to low hepatic engraftment efficiency of...


Author(s):  
Ludmila Vīksna ◽  
Jāzeps Keišs ◽  
Artūrs Sočņevs ◽  
Baiba Rozentāle ◽  
Māra Pilmane ◽  
...  

Novel Laboratory Tests in Assessment of Liver Function in Acute and Chronic Liver Diseases Liver biopsy in clinical practice has been widely used for the diagnosis and management of patients with liver diseases, particularly, with chronic liver diseases. However, liver biopsy is an invasive method with potential complications, sampling and interpretation errors. Therefore, noninvasive tests are being developed and introduced to replace liver biopsy. The aim of the present study was to identify the new noninvasive methods to be used for the assessment of liver structure and function, by use of the appropriate serum surrogate markers and to evaluate the clinical diagnostic and prognostic accuracy of these methods, including immunogenetic methods, in cases of acute and chronic liver diseases. The obtained data showed that serum markers of apoptosis (cytokeratin-18 neoepitope and citochrome c) and fibrosis (hyaluronic acid) should be included in viral and toxic liver damage management algorithms. The punctual identification of immunogenetic factors (HLA class II antigens) may prove to be useful in predicting disease evolution, and in guiding the appropriate therapy for patients with poor prognosis.


2016 ◽  
Vol 34 (5) ◽  
pp. 603-606 ◽  
Author(s):  
J. Gregory Fitz

The ∼90% probability of curing individual patients with hepatitis C virus (HCV)using direct-acting antivirals represents one of the most dramatic medical success stories of the modern era, and the journey from viral discovery to treatment occurred over just ∼25 years. The realities of the global burden of disease (2-3% of the world's population is infected), limited access to care and cost of treatment mean that HCV will continue to be a major problem for the next 25 years. But what if HCV (and hepatitis B) could be eradicated? Since liver transplantation and HCV management have been the mainstays of academic hepatology practice, where do we go from here? Unfortunately, we are in an era where the incidence and prevalence of liver diseases around the globe is increasing, and death from complications of cirrhosis is now among the top 10 causes in most countries; so hepatologists are expected to play a major role in the future. Despite remarkable progress, success at the population level is limited by the resource-intensive nature of caring for patients with end-stage disease. Accordingly, the major advances in the next decade are likely to focus on (i) the earlier identification of individuals and populations at higher risk for liver diseases, and (ii) initiation in high-risk populations of specific strategies for early detection and treatment of fibrosis, cancer and cirrhosis. The answers will lie in large part in the further exploration of the human genome in carefully phenotyped patients. Risk variants in the PNPLA3 gene represent the best example to date. The risk variants are common and are enriched in certain populations around the globe; and individuals that possess risk variants are more likely to have liver injury from fatty liver disease (even as children), alcohol and viral hepatitis. Further, those with liver injury are more likely to progress to cirrhosis and hepatoma. Similarly, in those with established liver disease, use of biomarkers and other strategies for early detection of fibrosis and hepatoma will pay dividends as the next generation of treatments focusing on (i) anti-fibrotic strategies and (ii) liver regeneration move to the forefront. There remains an important need to invest in hepatology as a growth industry even after the (unlikely) eradication of HCV.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Guiyang Wang ◽  
Peng Xiu ◽  
Fu Li ◽  
Cheng Xin ◽  
Kewei Li

Aim. To investigate the role of vitamin A in liver damage induced by bile duct ligation (BDL) in rats.Methods. Thirty male Wistar rats were randomly divided into three groups: SHAM group, BDL group, and BDL + VitA group . The concentrations of retinol and retinyl palmitate in the liver were analyzed using HPLC, and liver function was evaluated by the level of TBIL, ALT, AST, and ALP in serum. Hepatic oxidative status was estimated by measuring T-SOD, CAT, GSH, MDA, and AOPP. Nrf2 expression was assessed using immunohistochemistry and western blotting, and EMSA was performed to determine Nrf2 DNA-binding activity. The expression of the downstream factors such as Ho1 and Nqo1 was also examined using immunohistochemistry and western blotting assays.Results. Vitamin A treatment restored levels of retinoids in liver, improved liver function, alleviated oxidative stress, and facilitated the translocation of Nrf2 to the nucleus in the experimental obstructive jaundice. Vitamin A was also found to increase the expression of Nrf2 downstream proteins such as Ho1 and Nqo1.Conclusion. Vitamin A was here found to ameliorate cholestatic liver injury. This effect may be related to the activation of Nrf2/ARE pathway in bile duct ligation rats.


2021 ◽  
Vol 11 ◽  
pp. 151-163
Author(s):  
Adebowale Emmanuel Aladejana ◽  
Elizabeth Bosede Aladejana

Metabolic syndrome (MS) is a metabolic condition commonly associated with central adiposity and altered liver function parameters (LFPs). Several studies have suggested these altered LFPs as a result of fatty liver diseases (e.g., non-alcoholic fatty liver diseases) often prevalent in MS. Since altered LFPs are very common in MS, there is a possibility they can be used as predictors of MS. However, only a few studies have been carried out to evaluate this possibility. This study, therefore, aimed to evaluate the potential of LFPs as predictors or risk factors of MS. The study groups included 50 individuals diagnosed with MS (case group) and 50 apparently normal individuals (control) from Ibadan, Oyo State, Nigeria. Anthropometric measurements, phlebotomy, liver function tests, and lipid profile estimations were done using standard procedures. (The result and conclusion section has been omitted).


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