scholarly journals Increased Serum Levels of Activated Caspases in Murine and Human Biliary Atresia

2021 ◽  
Vol 10 (12) ◽  
pp. 2718
Author(s):  
Omid Madadi-Sanjani ◽  
Gunnar Bohlen ◽  
Fabian Wehrmann ◽  
Julia Andruszkow ◽  
Karim Khelif ◽  
...  
Keyword(s):  
Liver Injury ◽  
Biliary Atresia ◽  
Caspase 3 ◽  
Serum Levels ◽  
Healthy Individuals ◽  
Serological Detection ◽  
Caspase Activation ◽  
Hepatocyte Apoptosis ◽  
Non Invasive ◽  
Cholestatic Diseases

In biliary atresia (BA), apoptosis is part of the pathomechanism, which results in progressive liver fibrosis. There is increasing evidence suggesting that apoptotic liver injury can be non-invasively detected by measuring the caspase activity in the serum. The purpose of this study was to investigate whether serological detection of caspase activation mirrors apoptotic liver injury in the infective murine BA-model and represents a suitable biomarker for BA in humans. Analysis showed increased caspase-3 activity and apoptosis in the livers of cholestatic BALB/c mice, which correlated significantly with caspase activation in the serum. We then investigated caspase activation and apoptosis in liver tissues and sera from 26 BA patients, 23 age-matched healthy and 11 cholestatic newborns, due to other hepatopathies. Compared to healthy individuals, increased caspase activation in the liver samples of BA patients was present. Moreover, caspase-3 activity was significantly higher in sera from BA infants compared to patients with other cholestatic diseases (sensitivity 85%, specificity 91%). In conclusion, caspase activation and hepatocyte apoptosis play an important role in experimental and human BA. We demonstrated that serological detection of caspase activation represents a reliable non-invasive biomarker for monitoring disease activity in neonatal cholestatic liver diseases including BA.

scholarly journals Allopurinol ameliorates liver injury in type 1 diabetic rats through activating Nrf2

2021 ◽  
Vol 35 ◽  
pp. 205873842110314
Author(s):  
Fei Zeng ◽  
Jierong Luo ◽  
Hong Han ◽  
Wenjie Xie ◽  
Lingzhi Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Caspase 3 ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Heme Oxygenase 1 ◽  
Liver Protein ◽  
Lipid Peroxidation Product ◽  
Protein Expressions

Hyperglycemia-induced oxidative stress plays important roles in the development of non-alcoholic fatty liver disease (NAFLD), which is a common complication in diabetic patients. The Nrf2-Keap1 pathway is important for cell antioxidant protection, while its role in exogenous antioxidant mediated protection against NAFLD is unclear. We thus, postulated that antioxidant treatment with allopurinol (ALP) may attenuate diabetic liver injury and explored the underlying mechanisms. Control (C) and streptozotocin (STZ)-induced diabetes rats (D) were untreated or treated with ALP for 4 weeks starting at 1 week after diabetes induction. Serum levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), production of lipid peroxidation product malondialdehyde (MDA), and serum superoxide dismutase (SOD) were detected. Liver protein expressions of cleaved-caspase 3, IL-1β, nuclear factor-erythroid-2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), P62, Kelch-like ECH-associated protein 1 (Keap1), and LC3 were analyzed. In vitro, cultured rat normal hepatocytes BRL-3A were grouped to normal glucose (5.5 mM, NG) or high glucose (25 mM, HG) and treated with or without allopurinol (100 µM) for 48 h. Rats in the D group demonstrated liver injury evidenced as increased serum levels of ALT and AST. Diabetes increased apoptotic cell death, enhanced liver protein expressions of cleaved-caspase 3 and IL-1β with concomitantly increased production of MDA while serum SOD content was significantly reduced (all P < 0.05 vs C). In the meantime, protein levels of Nrf2, HO-1, and P62 were reduced while Keap1 and LC3 were increased in the untreated D group as compared to control ( P < 0.05 vs C). And all the above alterations were significantly attenuated by ALP. Similar to our findings obtained from in vivo study, we got the same results in in vitro experiments. It is concluded that ALP activates the Nrf2/p62 pathway to ameliorate oxidative stress and liver injury in diabetic rats.

scholarly journals Characterisation of the main PSA glycoforms in aggressive prostate cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anna Gratacós-Mulleras ◽  
Adrià Duran ◽  
Akram Asadi Shehni ◽  
Montserrat Ferrer-Batallé ◽  
Manel Ramírez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Blood Serum ◽  
Specific Antigen ◽  
Serum Levels ◽  
Neoplastic Progression ◽  
Healthy Individuals ◽  
Hydrophilic Interaction ◽  
Glycosylation Pattern ◽  
Non Invasive ◽  
Benign Prostate

Abstract Serum levels of prostate specific antigen (PSA) are commonly used for prostate cancer (PCa) detection. However, their lack of specificity to distinguish benign prostate pathologies from PCa, or indolent from aggressive PCa have prompted the study of new non-invasive PCa biomarkers. Aberrant glycosylation is involved in neoplastic progression and specific changes in PSA glycosylation pattern, as the reduction in the percentage of α2,6-sialic acid (SA) are associated with PCa aggressiveness. In this study, we have characterised the main sialylated PSA glycoforms from blood serum of aggressive PCa patients and have compared with those of standard PSA from healthy individuals’ seminal plasma. PSA was immunoprecipitated and α2,6-SA were separated from α2,3-SA glycoforms using SNA affinity chromatography. PSA N-glycans were released, labelled and analysed by hydrophilic interaction liquid chromatography combined with exoglycosidase digestions. The results showed that blood serum PSA sialylated glycoforms containing GalNAc residues were largely increased in aggressive PCa patients, whereas the disialylated core fucosylated biantennary structures with α2,6-SA, which are the major PSA glycoforms in standard PSA from healthy individuals, were markedly reduced in aggressive PCa. The identification of these main PSA glycoforms altered in aggressive PCa opens the way to design specific strategies to target them, which will be useful to improve PCa risk stratification.

Protective effect of Trillium tschonoskii saponin on CCl4-induced acute liver injury of rats through apoptosis inhibition

2016 ◽  
Vol 94 (12) ◽  
pp. 1291-1297 ◽  
Author(s):  
Hao Wu ◽  
Yong Qiu ◽  
Ziyang Shu ◽  
Xu Zhang ◽  
Renpeng Li ◽  
...  
Keyword(s):  
Liver Injury ◽  
Caspase 3 ◽  
Acute Liver Injury ◽  
Protective Role ◽  
High Dose ◽  
Dependent Manner ◽  
Hepatocyte Apoptosis ◽  
Liver Index ◽  
Tnf Α ◽  
Trillium Tschonoskii

To explore hepatoprotective role and underlying mechanisms of Trillium tschonoskii Maxim (TTM), 36 rats were randomly divided into control, CCl4-induced liver injury model, and biphenyl dimethyl dicarboxylate (DDB) and low-, moderate-, and high-dose TTM treatment groups. After CCl4-induced model establishment, the rats from DDB and TTM groups were administrated with DDB at 0.2 g/kg per day and TTM at 0.1, 0.5, and 1.0 g/kg per day, while the rats from control and model groups were administrated with saline. After 5 days of treatments, all rats were sacrificed for determining serum ALT and AST levels and liver index, examining histopathological changes in liver through HE and TUNEL staining, and evaluating TNF-α and IL-6 mRNA expression by real-time PCR, and caspase-3, Bcl-2, and Bax expression by Western blot. Results indicated that CCl4 could induce acute liver injury and abnormal liver function in rats with obvious hepatomegaly, increased liver index, high ALT and AST levels, up-regulated TNF-α and IL-6, and overexpressed Bax and caspase-3. However, DDB and TTM could execute protective role in CCl4-induced liver injury in rats through reducing ALT and AST levels, rescuing hepatomegaly, down-regulating inflammatory factors and inhibiting hepatocyte apoptosis in a dose-dependent manner. Therefore, TTM has obvious protective role in CCl4-induced liver injury of rats through inhibiting hepatocyte apoptosis.

scholarly journals The Role of Serotonin in Concanavalin A-Induced Liver Injury in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Qing Pang ◽  
Hao Jin ◽  
Xiquan Ke ◽  
Zhongran Man ◽  
Yong Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Inflammatory Response ◽  
Concanavalin A ◽  
Serum Levels ◽  
Hepatocyte Apoptosis ◽  
Con A ◽  
Serotonin 2A Receptor ◽  
Serotonin 2A

Serotonin is involved in the pathological processes of several liver diseases via the regulation of inflammatory response and oxidative stress. We aimed to investigate the role of serotonin in Concanavalin A- (Con A-) induced acute liver injury (ALI). ALI was induced in C57B/6 wild-type (WT) mice and tryptophan hydroxylase 1 (TPH1) knockout mice through tail vein injection of Con A (15 mg/kg body weight). Another group of TPH1 knockout ALI mice was supplied with 5-hydroxytryptophan (5-HTP) in advance to recover serotonin. The blood and liver tissues of mice were collected in all groups. Markedly increased serum levels of serotonin were identified after the injection of Con A. Increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and stronger hepatic tissue pathology were detected, suggesting that serotonin could mediate Con A-induced liver damage. Serotonin significantly facilitated the release of serum and intrahepatic inflammatory cytokines, including interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-17A (IL-17A), interferon-gamma (IFN-γ), and tumor necrosis-alpha (TNF-α), after the administration of Con A. In addition, serotonin significantly increased the intrahepatic levels of oxidative stress markers malonaldehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) and decreased antioxidant stress indicator glutathione (GSH) in Con A-treated mice. Additionally, serotonin promoted hepatocyte apoptosis and autophagy based on B-cell lymphoma-2 (Bcl-2), Bcl-2-asociated X protein (Bax), and Beclin-1 levels and TUNEL staining. More importantly, serotonin activated nuclear factor kappa B (NF-κB) and upregulated the hepatic expressions of high mobility group protein B1 (HMGB1), toll-like receptor-4 (TLR4), and downstream molecules in Con A-mediated liver injury. Serotonin 2A receptor was upregulated in liver tissue after Con A injection, and serotonin 2A receptor antagonist Ketanserin protected against Con A-induced hepatitis. These results indicated that serotonin has the potential to aggravate Con A-induced ALI via the promotion of inflammatory response, oxidative stress injury, and hepatocyte apoptosis and the activation of hepatic HMGB1-TLR signaling pathway and serotonin 2A receptor.

Time course of serum levels of leukemia inhibitory factor (LIF) and soluble LIF receptor (sLIF-R) in development of stage II essential hypertension

2017 ◽  
pp. 63-69
Author(s):  
О.А. Радаева ◽  
А.С. Симбирцев
Keyword(s):  
Antihypertensive Therapy ◽  
Time Course ◽  
Pulse Wave ◽  
Antihypertensive Drugs ◽  
Peripheral Resistance ◽  
Serum Levels ◽  
Stage Ii ◽  
Healthy Individuals ◽  
Vasoactive Substances ◽  
Essential Arterial Hypertension

Цель - изучение сывороточных уровней LIF, sLIr и их соотношение с гемодинамическими параметрами (ЧСС, САД, ДАД, ПАД, ЦАД, срАД, УО, МОК, ОПСС, СПВ) и содержанием вазоактивных веществ (AT II, ET-1, NO, ADMA, SDMA, eNOS, iNOS, NT-proСNP, NT-proBNP) у пациентов с эссенциальной артериальной гипертензией (ЭАГ) II стадии. Методы: количество LIF, sLIF-R/gp190 и вазоактивные вещества в сыворотке определяли иммуноферментным методом. Результаты: у пациентов с ЭАГ II стадии вне зависимости от проведения гипотензивной терапии была более высокая концентрация LIF (7,54 (2,8) пг/мл, 7,5 (2,1) пг/мл), по сравнению с условно здоровыми - 1,25 (0,5) пг/мл, р<0,001. При этом у пациентов, не получавших гипотензивные препараты, увеличивался уровень sLIr - (5800 (1470 pg/ml)) по сравнению с больными на фоне гипотензивной терапии (4100 (1380) пг/мл, р<0,001) и условно здоровыми (3800 (1100) пг/мл, р<0,001). При уровне sLIF-R выше 4800 пг/мл обнаруживали связь с увеличением содержания в сыворотке iNOS, NT-proBNP, ADMA, SDMA, (r = 0,5-0,8, р<0,05-0,001) и уменьшением уровня eNOS (r = -0,56-0,86, р<0,05-0,001), что соответствует прогрессированию заболевания. Корреляции между LIF и указанными вазоактивными веществами выявлено не было, что дает основание предполагать, что sLIFr вызывает собственные патогенетические эффекты помимо антагонистической активности по отношению к LIF. Aim. To study levels of serum LIF and sLIF-R and their correlations with hemodynamic parameters (heart rate, systolic BP, diastolic BP, pulse pressure, central BP, mean BP, stroke volume, total peripheral resistance, and pulse wave velocity) and vasoactive substances (AT II, ET-1, NO, ADMA, SDMA, eNOS, iNOS, NT-proСNP, and NT-proBNP) in patients with stage II essential arterial hypertension (EAH). Methods. Serum levels of LIF and sLIF-R/gp190 were measured using ELISA in 180 patients with stage II ЕAН. Results: Patients with EAH II (with or without antihypertensive therapy) had higher serum levels of LIF (7.54 (2.8) pg/ml and 7.5 (2.1) pg/ml, respectively) compared to healthy individuals (1.25 (0.5) pg/ml), р<0.001. Patients not receiving a therapy had higher serum levels of sLIF-R (5800 (1470 pg/ml) than patients receiving antihypertensive drugs (4100 (1380) pg/ml, р<0.001) and healthy individual (3800 (1100) pg/ml, р<0.001). In patients with EAH, sLIF-R levels higher than 4800 pg/ml correlated with increases in iNOS, NT-proBNP, ADMA, and SDMA (r = 0.5-0.8, р<0.05-0.001) and decreases in eNOS (r = -0.56-0.86, р<0.05-0.001), which corresponded to disease progression. LIF did not show any significant correlations with these vasoactive substances, which suggested that sLIF-R exerted its own pathogenetic effects besides antagonizing LIF. Generally, this trend was typical for patients with EAH (II stage) without antihypertensive therapy.

scholarly journals Serum Anti-Collagen IV IgM and IgG Antibodies as Indicators of Low Vascular Turnover of Collagen IV in Patients with Long-Term Complications of Type 2 Diabetes

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 900
Author(s):  
Krasimir Kostov ◽  
Alexander Blazhev
Keyword(s):  
Type 2 Diabetes ◽  
Serum Levels ◽  
Vascular Wall ◽  
Collagen Iv ◽  
Collagen Type Iv ◽  
Non Invasive ◽  
Type Iv ◽  
Antibody Levels

Thickening of the vascular basement membrane (BM) is a fundamental structural change in the small blood vessels in diabetes. Collagen type IV (CIV) is a major component of the BMs, and monitoring the turnover of this protein in type 2 diabetes (T2D) can provide important information about the mechanisms of vascular damage. The aim of the study was through the use of non-invasive biomarkers of CIV (autoantibodies, derivative peptides, and immune complexes) to investigate vascular turnover of CIV in patients with long-term complications of T2D. We measured serum levels of these biomarkers in 59 T2D patients with micro- and/or macrovascular complications and 20 healthy controls using an ELISA. Matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) were also tested. In the T2D group, significantly lower levels of CIV markers and significantly higher levels of MMP-2 and MMP-9 were found compared to controls. A significant positive correlation was found between IgM antibody levels against CIV and MMP-2. These findings suggest that vascular metabolism of CIV is decreased in T2D with long-term complications and show that a positive linear relationship exists between MMP-2 levels and CIV turnover in the vascular wall.

scholarly journals Serum sCD25 Protein as a Predictor of Lack of Long-Term Benefits from Immunotherapy in Non-Small Cell Lung Cancer: A Pilot Study

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3702
Author(s):  
Anna Siemiątkowska ◽  
Maciej Bryl ◽  
Katarzyna Kosicka-Noworzyń ◽  
Jakub Tvrdoň ◽  
Iwona Gołda-Gocka ◽  
...  
Keyword(s):  
Treatment Cycle ◽  
Small Cell Lung Carcinoma ◽  
Interleukin 2 ◽  
Serum Levels ◽  
Small Cell ◽  
Soluble Form ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Non Invasive

Prognosis of advanced non-small cell lung carcinoma (NSCLC) is poor. Even though it can improve with anti-PD-1/PD-L1 agents, most patients do not respond to treatment. We hypothesized that the serum soluble form of the unit α of the interleukin-2 receptor (sCD25) could be used as a biomarker of successful immunotherapy in NSCLC. We recruited patients dosed with atezolizumab (n = 42) or pembrolizumab (n = 20) and collected samples at baseline and during the treatment. Levels of sCD25 were quantified with the ELISA kits. Patients with a high sCD25 at baseline (sCD25.0 ≥ 5.99 ng/mL) or/and at the end of the fourth treatment cycle (sCD25.4 ≥ 7.73 ng/mL) progressed faster and lived shorter without the disease progression and serious toxicity. None of the patients with high sCD25 at both time points continued therapy longer than 9.3 months, while almost 40% of patients with low sCD25 were treated for ≥12.3 months. There was a 6.3-times higher incidence of treatment failure (HR = 6.33, 95% CI: 2.10–19.06, p = 0.001) and a 6.5-times higher incidence of progression (HR = 6.50, 95% CI: 2.04–20.73, p = 0.002) in patients with high compared with low sCD25.0 and sCD25.4. Serum levels of sCD25 may serve as a non-invasive biomarker of long-term benefits from the anti-PD-1/PD-L1s in NSCLC.

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