Immunohistochemical Expression of Oxidative Stress and Apoptosis Markers in Archived Liver Specimens from Dogs with Chronic Hepatitis

Yamkate, Punyamanee; Lidbury, Jonathan A.; Steiner, Jöerg M.; Suchodolski, Jan S.; Giaretta, Paula R.

doi:10.1016/j.jcpa.2022.02.005

Cited by 4 publications

(3 citation statements)

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“…Another cell death way for inflammatory cells can occur is through cuprizone demyelination and is exhibited in two types: 1) internal death: oxidative stress caused by the alteration of cuprizone contributes to cell body damage of oligodendrocytes; 2) external death: accumulation of immune responses due to disruption of pro-inflammatory cytokines and regulators ( Pasquini et al, 2007 ; Stys et al, 2012 ; Hooijmans et al, 2019 ; Zirngibl et al, 2022 ). Furthermore, the hepatic copper scores were correlated to hepatic neuroinflammatory, apoptosis, malondialdehyde, and fibrosis in various liver diseases ( Yamkate et al, 2022 ), and excessive accumulation of copper can could inhibit mitophagy and promote apoptosis in hepatocytes ( Yu et al, 2021 ). Excitingly, an increasing number of studies have focused on copper-induced cell death.…”

Section: Discussionmentioning

confidence: 99%

Cuproptosis-related gene signature correlates with the tumor immune features and predicts the prognosis of early-stage lung adenocarcinoma patients

Tang

Zhang

et al. 2022

Front. Genet.

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Background: Although a majority of early-stage lung adenocarcinoma (es-LUAD) patients have a favorable prognosis, there are still some cases with a risk of recurrence and metastasis. Cuproptosis is a new form of death that differs from other programmed cell death. However, no study has been reported for setting a prognostic model of es-LUAD using cuproptosis pattern-related genes.Methods: Using multiple R packages, the data from the GEO database was processed, and es-LUAD patients was classified into two patterns based on cuproptosis-related genes. Key differentially expressed genes (DEGs) in the two patterns were screened to construct a prognostic signature to assess differences in biological processes and immunotherapy responses in es-LUAD. Tumor microenvironment (TME) in es-LUAD was analyzed using algorithms such as TIMER and ssGSEA. Then, a more accurate nomogram was constructed by combining risk scores with clinical factors.Results: Functional enrichment analysis revealed that DEGs in two patterns were correlated with organelle fission, nuclear division, chromosome segregation, and cycle-related pathways. Univariate Cox regression and Lasso-Cox regression analyses identified six prognostic genes: ASPM, CCNB2, CDC45, CHEK1, NCAPG, and SPAG5. Based on the constructed model, we found that the high-risk group patients had higher expression of immune checkpoints (CTLA4, LAG3, PD-L1, TIGIT and TIM3), and a lower abundance of immune cells. Lastly, the nomogram was highly accurate in predicting the 1-, 3-, and 5-year survival status of patients with es-LUAD based on risk scores and clinical factors.Conclusion: The cuproptosis pattern-related signature can serve as a potential marker for clinical decision-making. It has huge potential in the future to guide the frequency of follow-up and adjuvant therapy for es-LUAD patients.

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Section: Discussionmentioning

confidence: 99%

Cuproptosis-related gene signature correlates with the tumor immune features and predicts the prognosis of early-stage lung adenocarcinoma patients

Tang

Zhang

et al. 2022

Front. Genet.

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“…Another study in humans found that a single serum marker of oxidative stress was able to distinguish between cirrhotic patients with and without mild HE signs [ 27 ]. Oxidative stress is generally considered an important factor in the pathogenesis of chronic liver disease in dogs [ 28 ], but the role it plays in the pathogenesis of HE requires greater investigation [ 29 ]. While we did not assess signs of HE in our cohort of CPSS dogs, it would be interesting in future studies to determine if there is a correlation between urinary F 2 -IsoP concentrations and clinical severity of HE.…”

Section: Discussionmentioning

confidence: 99%

Urinary 15-F2t-Isoprostane Concentrations in Dogs with Liver Disease

Phillips

Steiner

Suchodolski

et al. 2023

Veterinary Sciences

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Isoprostanes are stable end products of lipid peroxidation that can be used as markers of oxidative stress. It was previously reported that a cohort of dogs with various liver diseases had increased urinary isoprostane concentrations compared to healthy control (HC) dogs. The aim of this study was to measure and report urinary isoprostane concentrations in dogs with different types of liver diseases. Urine was collected from 21 HC dogs and from 40 dogs with liver disease, including 25 with chronic hepatitis (CH), 7 with steroid hepatopathy (SH), and 8 with a congenital portosystemic shunt (CPSS). In this prospective, observational study, urinary 15-F2t-isoprostane (F2-IsoP) concentrations were measured by liquid chromatography/mass spectrometry and normalized to urinary creatinine concentrations. Concentrations were compared between groups using a Kruskal–Wallis test followed by Dunn’s multiple comparisons tests. Significance was set at p < 0.05. The median (range) urinary F2-IsoP to creatinine ratios (ng/mg UCr) were 3.6 (2.2–12.4) for HC dogs, 5.7 (2.4–11.3) for dogs with CH, 4.8 (2.4–8.6) for dogs with SH, and 12.5 (2.9–22.9) for dogs with CPSS. CPSS dogs had significantly higher urinary F2-IsoP concentrations than HC dogs (p = 0.004), suggesting increased oxidative stress among this cohort.

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“… 26 , 27 An overall increase in hepatic copper content has been reported in several studies over the last several years in both breeds that are and those that are not predisposed to copper‐associated hepatitis. 16 , 17 , 28 , 29 , 30 , 31 , 32 , 33 These increases in hepatic copper concentration may reflect the higher concentrations of copper in dog foods that have accompanied an increase in the bioavailability of copper additives and the popularity of boutique diets with high copper concentrations.…”

Section: Discussionmentioning

confidence: 99%

Characterization of clinical presentation, histological features, ultrasonographic findings, and survival in 29 dogs with granulomatous hepatitis

Prentice,

Callahan‐Clark,

Parry

et al. 2023

Veterinary Internal Medicne

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BackgroundGranulomatous hepatitis (GH) is a form of chronic hepatitis (CH) in dogs for which limited information is published.HypothesisDescribe the clinical presentation, clinical pathology, ultrasound, and hepatic histopathology findings and to report survival times in dogs with GH.AnimalsTwenty‐nine client‐owned dogs with GH.MethodsRetrospective observational study. Pathology records were searched. Inclusion criteria included a histopathologic diagnosis of GH, absence of an identified etiology or evidence of extrahepatic granulomatous disease, and a medical record available for review. Clinical presentation, clinical pathologic findings, treatment protocols, and survival times were recorded. Available hepatic biopsy material was graded and scored, and ultrasound evaluations reviewed.ResultsThe median age was 7 years (range, 0.66‐12 years). Nineteen breeds were represented. Decreased appetite (19/29), lethargy (16/29), and fever (13/29) were seen most commonly. All dogs had increased serum transaminase activities, whereas 21/29 and 12/24 had hyperbilirubinemia and neutrophilia, respectively. Ultrasonographic findings included hepatomegaly (12/22), nodular parenchymal lesions (9/22), and hyperechoic parenchymal bands (8/22). Histopathologic necroinflammatory scores were moderate to severe in 16/19 dogs, and fibrosis scores were mild in 14/19 dogs. Treatments varied and included antibiotics, immunosuppressive drugs, and hepatoprotectants. Overall median survival was 635 days (range, 1‐2482 days).Conclusion and Clinical ImportanceGranulomatous hepatitis in dogs is associated with high histopathologic grade, fever, neutrophilia, and a high incidence of hepatomegaly and focal parenchymal lesions on ultrasound examination. Despite disease severity on presentation, dogs with GH can have a good outcome with prolonged survival.

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Immunohistochemical Expression of Oxidative Stress and Apoptosis Markers in Archived Liver Specimens from Dogs with Chronic Hepatitis

Cited by 4 publications

References 30 publications

Cuproptosis-related gene signature correlates with the tumor immune features and predicts the prognosis of early-stage lung adenocarcinoma patients

Cuproptosis-related gene signature correlates with the tumor immune features and predicts the prognosis of early-stage lung adenocarcinoma patients

Urinary 15-F2t-Isoprostane Concentrations in Dogs with Liver Disease

Characterization of clinical presentation, histological features, ultrasonographic findings, and survival in 29 dogs with granulomatous hepatitis

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