scholarly journals Protective role of melatonin in early‐stage and end‐stage liver cirrhosis

2019 ◽  
Vol 23 (11) ◽  
pp. 7151-7162 ◽  
Author(s):  
Chenxia Hu ◽  
Lingfei Zhao ◽  
Jingjing Tao ◽  
Lanjuan Li
Keyword(s):  
Liver Cirrhosis ◽  
Early Stage ◽  
Protective Role ◽  
End Stage

scholarly journals Serum Amyloid Beta42 Is Not Eliminated by the Cirrhotic Liver: A Pilot Study

2021 ◽  
Vol 10 (12) ◽  
pp. 2669
Author(s):  
Reiner Wiest ◽  
Thomas S. Weiss ◽  
Lusine Danielyan ◽  
Christa Buechler
Keyword(s):  
Liver Cirrhosis ◽  
Hepatic Clearance ◽  
Protective Role ◽  
Tissue Growth ◽  
Cirrhotic Liver ◽  
Diabetic Patients ◽  
Peripheral Clearance ◽  
End Stage ◽  
The Brain

Amyloid-beta (Aβ) deposition in the brain is the main pathological hallmark of Alzheimer disease. Peripheral clearance of Aβ may possibly also lower brain levels. Recent evidence suggested that hepatic clearance of Aβ42 is impaired in liver cirrhosis. To further test this hypothesis, serum Aβ42 was measured by ELISA in portal venous serum (PVS), systemic venous serum (SVS), and hepatic venous serum (HVS) of 20 patients with liver cirrhosis. Mean Aβ42 level was 24.7 ± 20.4 pg/mL in PVS, 21.2 ± 16.7 pg/mL in HVS, and 19.2 ± 11.7 pg/mL in SVS. Similar levels in the three blood compartments suggested that the cirrhotic liver does not clear Aβ42. Aβ42 was neither associated with the model of end-stage liver disease score nor the Child–Pugh score. Patients with abnormal creatinine or bilirubin levels or prolonged prothrombin time did not display higher Aβ42 levels. Patients with massive ascites and patients with large varices had serum Aβ42 levels similar to patients without these complications. Serum Aβ42 was negatively associated with connective tissue growth factor levels (r = −0.580, p = 0.007) and a protective role of Aβ42 in fibrogenesis was already described. Diabetic patients with liver cirrhosis had higher Aβ42 levels (p = 0.069 for PVS, p = 0.047 for HVS and p = 0.181 for SVS), which is in accordance with previous reports. Present analysis showed that the cirrhotic liver does not eliminate Aβ42. Further studies are needed to explore the association of liver cirrhosis, Aβ42 levels, and cognitive dysfunction.

scholarly journals Protective Role of Naturally Occurring Interleukin-17A-Producing γδ T Cells in the Lung at the Early Stage of Systemic Candidiasis in Mice

2011 ◽  
Vol 79 (11) ◽  
pp. 4503-4510 ◽  
Author(s):  
Takashi Dejima ◽  
Kensuke Shibata ◽  
Hisakata Yamada ◽  
Hiromitsu Hara ◽  
Yoichiro Iwakura ◽  
...  
Keyword(s):  
T Cells ◽  
Early Stage ◽  
Γδ T Cells ◽  
Protective Role ◽  
Dependent Manner ◽  
Peripheral Tissues ◽  
Content Type ◽  
Naturally Occurring ◽  
Interleukin 17A

ABSTRACTInterleukin-17A (IL-17A)-producing γδ T cells differentiate in the fetal thymus and reside in the peripheral tissues, such as the lungs of naïve adult mice. We show here that naturally occurring γδ T cells play a protective role in the lung at a very early stage after systemic infection withCandida albicans.Selective depletion of neutrophils byin vivoadministration of anti-Ly6G monoclonal antibody (MAb) impaired fungal clearance more prominently in the lung than in the kidney 24 h after intravenous infection withC. albicans.Rapid and transient production of IL-23 was detected in the lung at 12 h, preceding IL-17A production and the influx of neutrophils, which reached a peak at 24 h after infection. IL-17A knockout (KO) mice showed reduced infiltration of neutrophils concurrently with impaired fungal clearance in the lung after infection. The major source of IL-17A was the γδ T cell population in the lung, and Cδ KO mice showed little IL-17A production and reduced neutrophil infiltration after infection. Early IL-23 production in a TLR2/MyD88-dependent manner and IL-23-triggered tyrosine kinase 2 (Tyk2) signaling were essential for IL-17A production by γδ T cells. Thus, our study demonstrated a novel role of naturally occurring IL-17A-producing γδ T cells in the first line of host defense againstC. albicansinfection.

scholarly journals Investigation of Bacteremia due toAeromonasSpecies and Comparison with That due to Enterobacteria in Patients with Liver Cirrhosis

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Toru Shizuma ◽  
Chiharu Tanaka ◽  
Hidezo Mori ◽  
Naoto Fukuyama
Keyword(s):  
Liver Cirrhosis ◽  
Japanese Patients ◽  
Meld Score ◽  
Short Term ◽  
E Coli ◽  
End Stage Liver Disease ◽  
Short Term Mortality ◽  
Clinical Background ◽  
End Stage

Background. The role ofAeromonasspecies (sp.) in bacteremia in Japanese patients with liver cirrhosis is poorly understood.Aim. To establish the importance ofAeromonassp. as a cause of bacteremia in patients with liver cirrhosis.Methods. Clinical and serological features and short-term prognosis were retrospectively investigated and compared in Japanese patients with bacteremia due toAeromonassp. () and due to enterobacteria (E. coli, Klebsiellasp., andEnterobactersp.) ().Results. There were no significant differences in patients’ clinical background, renal dysfunction, or short-term mortality rate between the two groups. However, in theAeromonasgroup, the model for end-stage liver disease (MELD) score and Child-Pugh score were significantly higher than in the enterobacteria group.Conclusion. These results indicate that the severity of liver dysfunction inAeromonas-induced bacteremia is greater than that in enterobacteria-induced bacteremia in Japanese patients with liver cirrhosis.

CD133+ Pluripotent Stem Cells for the Treatment of Chronic Liver Failure.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1185-1185
Author(s):  
Lucia Catani ◽  
Stefania Lorenzini ◽  
Rosaria Giordano ◽  
Paolo Caraceni ◽  
Maria Rosa Motta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Cirrhosis ◽  
Liver Disease ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Chronic Liver ◽  
Peripheral Blood Stem Cells ◽  
End Stage Liver Disease ◽  
End Stage

Abstract Abstract 1185 Background. The potential role of bone marrow (BM)-derived stem cells (SCs) in patients with end-stage liver disease has been addressed by our group in four studies. Main objectives were: 1) to assess stem/progenitor cell mobilization in 24 patients receiving orthotopic liver transplantation (OLT); 2) to evaluate whether G-CSF can be safely administered to patients with liver cirrhosis in order to expand and mobilize BM-derived SCs; 3) to investigate the effects of transplantation of human G-CSF-mobilized CD34+ and CD133+ SCs in mice with chronic liver injury and fibrosis; 4) to evaluate the feasibility and the safety of the purification and intrahepatic reinfusion of increasing numbers of autologous BM-derived G-CSF-mobilized CD133+ SCs in patients with end-stage liver disease. Methods. 1) Flow cytometry analysis, clonogenic assays and RT-PCR have been performed after OLT; 2) 18 patients with advanced liver disease were consecutively treated with increasing doses of G-CSF starting from 2 μg/kg/daily; 3) C57BL/6N mice received CCl4 by inhalation for thirteen weeks and were treated with Cyclosporin-A. Transplantation was performed by injection (tail vein) of 106 CD34+ or CD133+ SCs of three cirrhotic patients. After four weeks from transplantation all mice were sacrificed; 4) G-CSF at 7.5μg/Kg/b.i.d. is administered subcutaneosly (sc) from day 1 until the completion of peripheral blood stem cells (PBSC) collection. Collection of PBSC will begin on day + 4 only if the concentration of CD133+ cells is 38/mL. PB mononuclear cells obtained from mobilized standard-volume leukapheresis will be incubated with Macs colloidal superparamagnetic CD133 microbeads. CliniMacs device is used for the positive selection of CD133+ SCs under GMP conditions. At least 4 weeks after SC mobilization, collection and cryopreservation, highly purified autologous G-CSF-mobilized CD133+ cells are re-infused through the hepatic artery by transfemoral or transbranchial arteriography. CD133+ cells are administered to patients starting from 5×104/Kg patient's body weight and increased every 3 patients. The maximum infused cell dose will be 1×106/kg. G-CSF at 5μg/Kg/day is administered sc for 3 days after the reinfusion of SCs for their expansion and to induce a selective proliferative advantage of reinfused cells in vivo. Results and Discussion. 1) We demonstrated that both early subsets of the hematopoietic SC compartment (CD34+/CD90+ cells) and more mature committed progenitors (CFU-C) were mobilized into PB after OLT. We also demonstrated the release from the BM of liver-committed HSCs co-expressing epithelial markers after OLT; 2) We show that the administration of G-CSF to patients with liver cirrhosis is safe and feasible and allows the mobilization and collection of BM-derived SCs at the dose of 15 mg/kg/day. 3) We demonstrated that mice transplanted with either CD133+ or CD34+ human cells appear to have less fibrotic septa than mice without SC transplantation, suggesting the potential therapeutic role of human SCs on the recovery of liver fibrosis. 4) Up to date, three patients with end stage liver disease have been successfully mobilized with G-CSF and highly purified autologous CD133+ SCs have been re-infused. The number of collected CD133+ SCs is 0,7, 0,2 and 0.35×106/Kg, respectively. The number of the re-infused highly purified CD133+ SCs is 4.7, 5.0 and 5.4×104/Kg, respectively. No adverse events have been recorded during mobilization or intrahepatic SCs re-infusion. Updated results on current patients and future patients will be presented at the Meeting. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Pretreatment with Roxadustat (FG-4592) Attenuates Folic Acid-Induced Kidney Injury through Antiferroptosis via Akt/GSK-3β/Nrf2 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Xue Li ◽  
Yu Zou ◽  
Jia Xing ◽  
Yuan-Yuan Fu ◽  
Kai-Yue Wang ◽  
...  
Keyword(s):  
Renal Function ◽  
Folic Acid ◽  
Nuclear Translocation ◽  
Early Stage ◽  
Kidney Injury ◽  
Protective Role ◽  
Iron Accumulation ◽  
Inflammatory Factors ◽  
Nrf2 Activation

Folic acid- (FA-) induced kidney injury is characterized by the tubule damage due to the disturbance of the antioxidant system and subsequent interstitial fibrosis. FG-4592 is an inhibitor of prolyl hydroxylase of hypoxia-inducible factor (HIF), an antioxidant factor. The present study investigated the protective role of FG-4592 pretreatment at the early stage of the kidney injury and long-term impact on the progression of renal fibrosis. FG-4592 was administrated two days before FA injection in mice. On the second day after FA injection, the mice with FG-4592 pretreatment showed an improved renal function, compared with those without FG-4592 pretreatment, indicated by biochemical and histological parameters; meanwhile, the cellular content of iron, malondialdehyde, and 4-hydroxynonenal histologically decreased, implying the suppression of iron accumulation and lipid peroxidation. Simultaneously, upregulation of HIF-1α was found, along with Nrf2 activation, which was reflected by increased nuclear translocation and high-expression of downstream proteins, including heme-oxygenase1, glutathione peroxidase4, and cystine/glutamate transporter, as well as ferroportin. Correspondingly, the elevated levels of antioxidative enzymes and glutathione, as well as reduced iron accumulation, were observed, suggesting a lower risk of occurrence of ferroptosis with FG-4592 pretreatment. This was confirmed by reversed pathological parameters and improved renal function in FA-treated mice with the administration of ferrostatin-1, a specific ferroptosis inhibitor. Furthermore, a signal pathway study indicated that Nrf2 activation was associated with increased phosphorylation of Akt and GSK-3β, verified by the use of an inhibitor of the PI3K that phosphorylates Akt. Moreover, FG-4592 pretreatment also decreased macrophage infiltration and expression of inflammatory factors TNF-α and IL-1β. On the 14th day after FA injection, FG-4592 pretreatment decreased collagen deposition and expression of fibrosis biomarkers. These findings suggest that the protective role of FG-4592 pretreatment is achieved mainly by decreasing ferroptosis at the early stage of FA-induced kidney injury via Akt/GSK-3β-mediated Nrf2 activation, which retards the fibrosis progression.

scholarly journals Does the End Justify the Means? The Role of Organizational Communication among Work-from-Home Employees during the COVID-19 Pandemic

2021 ◽  
Vol 18 (8) ◽  
pp. 3933
Author(s):  
Margherita Zito ◽  
Emanuela Ingusci ◽  
Claudio G. Cortese ◽  
Maria Luisa Giancaspro ◽  
Amelia Manuti ◽  
...  
Keyword(s):  
Organizational Communication ◽  
Self Efficacy ◽  
Early Stage ◽  
Protective Role ◽  
Structural Equations ◽  
Current Crisis ◽  
Personal Resource ◽  
Physical Disorders ◽  
Working Processes

During the first months of 2020, the world, and Italy at an early stage, went through the Covid-19 emergency that had a great impact on individual and collective health, but also on working processes. The mandatory remote working and the constant use of technology for employees raised different implications related to technostress and psycho-physical disorders. This study aimed to detect, in such a period of crisis and changes, the role of organizational communication considering the mediating role of both technostress and self-efficacy, with psycho-physical disorders as outcome. The research involved 530 workers working from home. A Structural Equations Model was estimated, revealing that organizational communication is positively associated with self-efficacy and negatively with technostress and psycho-physical disorders. As mediators, technostress is positively associated with psycho-physical disorders, whereas self-efficacy is negatively associated. As regards mediated effects, results showed negative associations between organizational communication and psycho-physical disorders through both technostress and self-efficacy. This study highlighted the potential protective role of organizational communication that could buffer the effect of technostress and enhance a personal resource, self-efficacy, which is functional to the reduction of psycho-physical disorders. This study contributed to literature underlying the role of communication in the current crisis and consequent reorganization of the working processes.

scholarly journals Polymorphisms in the Genes Encoding for Human Kinin Receptors and the Risk of End-Stage Renal Failure

1999 ◽  
Vol 10 (10) ◽  
pp. 2120-2124
Author(s):  
MARCIN J. ZYCHMA ◽  
JANUSZ GUMPRECHT ◽  
EWA ZUKOWSKA-SZCZECHOWSKA ◽  
WLADYSLAW GRZESZCZAK
Keyword(s):  
Promoter Region ◽  
Receptor Gene ◽  
Protective Role ◽  
R Gene ◽  
Exon 2 ◽  
Kinin Receptors ◽  
Receptor Gene Polymorphisms ◽  
Stage Renal Disease ◽  
End Stage

Abstract. There is evidence that environmental factors and genetic predisposition affect the development of end-stage renal disease (ESRD). The role of kinin peptides in renal pathology has been also suggested, and a nephroprotective effect of kinins, mediated by B1and B2kinin receptors, has been postulated. Recently, two novel sequence differences in the B1R gene were identified, and the C allele of the G→C substitution at position -699 in the promoter region of the B1R gene was found to be less frequent among patients with ESRD compared with healthy control subjects. In this study, the association between B1R and B2R polymorphisms and ESRD was examined using a family-based study design: transmission/disequilibrium test. B1R gene G→C substitution at position -699 in the promoter region and B2R gene C→T transition at position 181 in exon 2 were genotyped in 247 family trios: offspring affected with ESRD and both parents. The less common alleles of both polymorphisms (B1R C allele and B2R T allele) were transmitted from heterozygous parents to offspring affected with ESRD less frequently than expected (37 and 36%, respectively;P< 0.05). In conclusion, results obtained in this study support a hypothesis of the protective role of bradykinin receptor gene polymorphisms in the development of ESRD.

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