386-P: Acute Hypoglycemia Does Not Alter Serum Levels of Amyloid-Related Proteins Associated with Dementia

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 386-P
Author(s):  
ABU MOIN ◽  
THOZHUKAT SATHYAPALAN ◽  
STEPHEN ATKIN ◽  
ALEXANDRA E. BUTLER
Keyword(s):  
Serum Levels ◽  
Acute Hypoglycemia ◽  
Related Proteins

scholarly journals Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2529
Author(s):  
Haeyeop Kim ◽  
Woo Seok Yang ◽  
Khin Myo Htwe ◽  
Mi-Nam Lee ◽  
Young-Dong Kim ◽  
...  
Keyword(s):  
Ethanol Extract ◽  
Serum Levels ◽  
Hepatoprotective Activity ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Related Proteins ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

scholarly journals Fucoidan Alleviates Acetaminophen-Induced Hepatotoxicity via Oxidative Stress Inhibition and Nrf2 Translocation

2018 ◽  
Vol 19 (12) ◽  
pp. 4050 ◽  
Author(s):  
Yu-qin Wang ◽  
Jin-ge Wei ◽  
Meng-jue Tu ◽  
Jian-guo Gu ◽  
Wei Zhang
Keyword(s):  
Oxidative Stress ◽  
Serum Levels ◽  
Sulfated Polysaccharide ◽  
Intragastric Administration ◽  
Related Factor ◽  
Cell Nuclei ◽  
Brown Seaweeds ◽  
Wide Range ◽  
Related Proteins ◽  
Apap Hepatotoxicity

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that leads to severe hepatotoxicity at excessive doses. Fucoidan, a sulfated polysaccharide derived from brown seaweeds, possesses a wide range of pharmacological properties. However, the impacts of fucoidan on APAP-induced liver injury have not been sufficiently addressed. In the present study, male Institute of Cancer Research (ICR) mice aged 6 weeks were subjected to a single APAP (500 mg/kg) intraperitoneal injection after 7 days of fucoidan (100 or 200 mg/kg/day) or bicyclol intragastric administration. The mice continued to be administered fucoidan or bicyclol once per day, and were sacrificed at an indicated time. The indexes evaluated included liver pathological changes, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum, levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) in the liver, and related proteins levels (CYP2E1, pJNK and Bax). Furthermore, human hepatocyte HL-7702 cell line was used to elucidate the potential molecular mechanism of fucoidan. The mitochondrial membrane potential (MMP) and nuclear factor-erythroid 2-related factor (Nrf2) translocation in HL-7702 cells were determined. The results showed that fucoidan pretreatment reduced the levels of ALT, AST, ROS, and MDA, while it enhanced the levels of GSH, SOD, and CAT activities. Additionally, oxidative stress-induced phosphorylated c-Jun N-terminal protein kinase (JNK) and decreased MMP were attenuated by fucoidan. Although the nuclear Nrf2 was induced after APAP incubation, fucoidan further enhanced Nrf2 in cell nuclei and total expression of Nrf2. These results indicated that fucoidan ameliorated APAP hepatotoxicity, and the mechanism might be related to Nrf2-mediated oxidative stress.

scholarly journals Associations Between Common and Rare Exonic Genetic Variants and Serum Levels of 20 Cardiovascular-Related Proteins

2016 ◽  
Vol 9 (4) ◽  
pp. 375-383 ◽  
Author(s):  
Terry Solomon ◽  
Erin N. Smith ◽  
Hiroko Matsui ◽  
Sigrid K. Braekkan ◽  
Tom Wilsgaard ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Serum Levels ◽  
Related Proteins

scholarly journals Apigenin Attenuates Adriamycin-Induced Cardiomyocyte Apoptosis via the PI3K/AKT/mTOR Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Yu ◽  
Huirong Sun ◽  
Wenliang Zha ◽  
Weili Cui ◽  
Ling Xu ◽  
...  
Keyword(s):  
Treatment Group ◽  
Cardiac Injury ◽  
Serum Levels ◽  
Mtor Pathway ◽  
Cardiomyocyte Apoptosis ◽  
Control Group ◽  
Limiting Factor ◽  
High Dose ◽  
Induced Apoptosis ◽  
Related Proteins

Treatment with Adriamycin (ADR) is one of the major causes of chemotherapy-induced cardiotoxicity and therefore is the principal limiting factor in the effectiveness of chemotherapy for cancer patients. Apigenin (API) has been shown to play a cardioprotective role. The present study examined the effect of API on ADR-induced cardiotoxicity in mice. Sixty male Kunming mice were randomly divided into 4 groups: a control group, ADR model group, low-dose API treatment group (125 mg·kg−1), and high-dose API treatment group (250 mg·kg−1). Blood samples were taken to evaluate a spectrum of myocardial enzymes. Cardiomyocyte apoptosis was measured using a TUNEL assay, and cardiomyocyte autophagy was observed using electron microscopy. Moreover, apoptosis-related proteins, such as Bax and Bcl-2, autophagy-related proteins, including Beclin1 and LC3B, and PI3K/AKT/mTOR pathway-related proteins were examined with western blot. Our results demonstrate that ADR caused an increase in the serum levels of cardiac injury markers and enhanced cardiomyocyte apoptosis and autophagy. API administration prevented the effects associated with ADR-induced cardiotoxicity in mice and inhibited ADR-induced apoptosis and autophagy. API also promoted PI3K/AKT/mTOR pathway activity in ADR-treated mice. In conclusion, API may have a protective effect against ADR-induced cardiotoxicity by inhibiting apoptosis and autophagy via activation of the PI3K/AKT/mTOR pathway.

scholarly journals Increased Soluble Cytoplasmic Bcl-2 Protein Serum Levels and Expression and Decreased Fas Expression in Lymphocytes and Monocytes in Juvenile Dermatomyositis

2018 ◽  
Vol 45 (11) ◽  
pp. 1577-1580
Author(s):  
Bernadete L. Liphaus ◽  
Adriana E.M. Sallum ◽  
Nadia E. Aikawa ◽  
Maria Helena B. Kiss ◽  
Solange Carrasco ◽  
...  
Keyword(s):  
Juvenile Dermatomyositis ◽  
Serum Levels ◽  
Manual Muscle Testing ◽  
Healthy Controls ◽  
Peripheral Cell ◽  
Reactive Protein ◽  
Soluble Fas ◽  
Muscle Testing ◽  
Related Proteins ◽  
Protein Serum

Objective.To evaluate soluble Fas antigen (sFas), sFas ligand (sFasL), soluble tumor necrosis factor-related apoptosis-inducing ligand, and soluble cytoplasmic Bcl-2 protein (sBcl-2) serum levels, Fas and Bcl-2 expressions in T and B lymphocytes and monocytes and relations with erythrocyte sedimentation rate, C-reactive protein (CRP), Childhood Myositis Assessment Scale, and manual muscle testing in juvenile dermatomyositis (JDM).Methods.Serum levels were determined by ELISA and peripheral cell expressions by flow cytometry for patients with JDM or juvenile idiopathic arthritis (JIA), and healthy controls.Results.Patients with JDM had increased sBcl-2, which correlated with CRP. Expression of Bcl-2 was increased and expression of Fas was decreased in CD3+, CD4+, and CD8+ T lymphocytes compared with JIA and/or healthy controls.Conclusion.Patients with JDM presented a unique apoptosis-related proteins profile, which may contribute to disease development.

scholarly journals Amyloid-related protein changes associated with dementia differ according to severity of hypoglycemia

2021 ◽  
Vol 9 (1) ◽  
pp. e002211
Author(s):  
Abu Saleh Md Moin ◽  
Hassan Kahal ◽  
Ahmed Al-Qaissi ◽  
Nitya Kumar ◽  
Thozhukat Sathyapalan ◽  
...  
Keyword(s):  
Percentage Change ◽  
Related Protein ◽  
Control Subjects ◽  
Link Type ◽  
Increase Risk ◽  
Serum Amyloid A1 ◽  
Acute Hypoglycemia ◽  
Related Proteins ◽  
Design And Methods

IntroductionHypoglycemia in type 2 diabetes (T2D) may increase risk for Alzheimer’s disease (AD), but no data on changes in AD-related proteins with differing degrees of hypoglycemia exist. We hypothesized that milder prolonged hypoglycemia would cause greater AD-related protein changes versus severe transient hypoglycemia.Research design and methodsTwo prospective case-control induced hypoglycemia studies were compared: study 1, hypoglycemic clamp to 2.8 mmol/L (50 mg/dL) for 1 hour in 17 subjects (T2D (n=10), controls (n=7)); study 2, hypoglycemic clamp to 2.0 mmol/L (36 mg/dL) undertaken transiently and reversed in 46 subjects (T2D (n=23), controls (n=23)). Blood sampling at baseline, hypoglycemia and 24-hour post-hypoglycemia, with proteomic analysis of amyloid-related proteins performed.ResultsIn control subjects, the percentage change from baseline to hypoglycemia differed between study 1 and study 2 for 5 of 11 proteins in the AD-related panel: serum amyloid A1 (SAA1) (p=0.009), pappalysin (PAPPA) (p=0.002), apolipoprotein E2 (p=0.02), apolipoprotein E3 (p=0.03) and apolipoprotein E4 (p=0.02). In controls, the percentage change from baseline to 24 hours differed between studies for two proteins: SAA1 (p=0.003) and PAPPA (p=0.004); however, after Bonferroni correction only SAA1 and PAPPA remain significant. In T2D, there were no differential protein changes between the studies.ConclusionsThe differential changes in AD-related proteins were seen only in control subjects in response to iatrogenic induction of hypoglycemic insults of differing length and severity and may reflect a protective response that was absent in subjects with T2D. Milder prolonged hypoglycemia caused greater AD-related protein changes than severe acute hypoglycemia in control subjects.Trial registration numbersNCT02205996, NCT03102801.

scholarly journals Role of serum matrix metalloproteinase in the diagnosis of gastric cancer

2020 ◽  
Vol 36 (5) ◽  
Author(s):  
Jian Liu ◽  
Liya Zhou ◽  
Sanren Lin ◽  
Bei Yao
Keyword(s):  
Gastric Cancer ◽  
Matrix Metalloproteinase ◽  
Serum Levels ◽  
Gastric Disease ◽  
Antibody Array ◽  
Clinical Value ◽  
Serum Samples ◽  
Creative Commons ◽  
Related Proteins

Objective: To determine the clinical value of a matrix metalloproteinase (MMP) antibody array in diagnosing gastric cancer (GC). Methods: In this prospective study, serum samples of patients with GC (n=66) and non-neoplastic gastric disease (NGD; n=34) were collected between November 2017 and July 2018. The quantitative measurement of 10 MMP-related proteins was done using MMP arrays and compared between the two groups. Results: The serum levels of MMPs 3, 8, 9 and tissue inhibitor of metalloproteinases (TIMPs) 1 and 2 were significantly higher in the GC group than in the NGD group (p<0.05). The area under curve (AUC) of the 10 MMP proteins for the diagnosis of GC varied between 0.500 and 0.658. The total AUC of all MMPs was 0.897 (95% CI: 0.837-0.957). The total AUC of the five MMPs (MMPs 3, 8, 9, and TIMPs 1 and 2) was 0.821 (95% CI: 0.733-0.909) for diagnosing GC. Also, the 10-factor and 5-factor predictive models had good diagnostic ability for early GC with an AUC of 0.865 (95% CI: 0.753-0.977) and 0.749 (95% CI: 0.600-0.898), respectively. Conclusions: The detection of multiple serum MMPs with protein biochip technology is promising to be used as a novel non-invasive tool for facilitating early diagnosis or screening of GC. doi: https://doi.org/10.12669/pjms.36.5.2059 How to cite this:Liu J, Zhou L, Lin S, Yao B. Role of serum matrix metalloproteinase in the diagnosis of gastric cancer. Pak J Med Sci. 2020;36(5):1025-1031. doi: https://doi.org/10.12669/pjms.36.5.2059 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Changes in pregnancy-related serum biomarkers early in gestation are associated with later development of preeclampsia

2018 ◽  
Author(s):  
Shiying Hao ◽  
Jin You ◽  
Lin Chen ◽  
Hui Zhao ◽  
Yujuan Huang ◽  
...  
Keyword(s):  
Normal Subjects ◽  
Serum Levels ◽  
Heme Oxygenase 1 ◽  
Related Protein ◽  
Protein Patterns ◽  
Protein Levels ◽  
Normal Human ◽  
Placental Protein ◽  
Related Proteins ◽  
Human And Mouse

ABSTRACTBackgroundPlacental protein expression plays a crucial biological role during normal and complicated pregnancies. We hypothesized that: (1) circulating pregnancy-associated, placenta-related protein levels throughout gestation reflect the uncomplicated, full-term temporal progression of human gestation, and effectively estimates gestational ages (GAs); (2) pregnancies with underlying placental pathology, such as preeclampsia (PE), are associated with disruptions in this GA estimation in early gestation; (3) malfunctions of this GA estimation can be employed to identify impending PE. In addition, to explore the underlying biology and PE etiology, we set to compare protein gestational patterns of human and mouse, using pregnant heme oxygenase-1 (HO-1) heterozygote (Het) mice, a mouse model reflecting PE-like symptoms.MethodsSerum levels of circulating placenta-related proteins – leptin (LEP), chorionic somatomammotropin hormone like 1 (CSHL1), elabela (ELA), activin A, soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF)– were quantified by ELISA in blood serially collected throughout human pregnancies (20 normal subjects with 66 samples, and 20 PE subjects with 61 samples). Linear multivariate analysis of the targeted serological protein levels was performed to estimate the normal GA. Logarithmic transformed mean-squared errors of GA estimations were used to identify impending PE. Then the human gestational protein patterns were compared to those in the pregnant HO-1 mice.ResultsAn elastic net (EN)-based gestational dating model was developed (R2 = 0.76) and validated (R2 = 0.61) using the serum levels of the 6 proteins at various GAs from women with normal uncomplicated pregnancies (n = 10 for training and n = 6 for validation). In pregnancies complicated by PE (n = 14), the EN model was not (R2 = −0.17) associated with GA at sampling in PE. Statistically significant deviations from the normal GA EN model estimations were observed in PE-associated pregnancies between GAs of 16–30 weeks (P = 0.01). The EN model developed with 5 proteins (ELA excluded due to the lack of robustness of the mouse ELA essay) performed similarly on normal human (R2 = 0.68) and WT mouse (R2 = 0.85) pregnancies. Disruptions of this model were observed in both human PE-associated (human: R2 = 0.27) and mouse HO-1 Het (mouse: R2 = 0.30) pregnancies. LEP out performed sFlt-1 and PlGF in differentiating impending PE at early human and late mouse gestations.ConclusionsAs revealed in both human and mouse GA EN analyses, temporal serological placenta-related protein patterns are tightly regulated throughout normal human pregnancies and can be significantly disrupted in pathologic PE states. LEP changes earlier during gestation than the well-established late GA PE biomarkers (sFlt-1 and PlGF). Our HO-1 Het mouse analysis provides direct evidence of the causative action of HO-1 deficiency in LEP upregulation in a PE-like murine model. Therefore, longitudinal analyses of pregnancy-related protein patterns in sera, may not only help in the exploration of underlying PE pathophysiology but also provide better clinical utility in PE assessment.

Molecular signature of coronary stent thrombosis: oxidative stress and innate immunity cells

2017 ◽  
Vol 117 (09) ◽  
pp. 1816-1827 ◽  
Author(s):  
Judit Cubedo ◽  
Ana Blasco ◽  
Teresa Padró ◽  
Ilaria Ramaiola ◽  
Oriol Juan-Babot ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stent Thrombosis ◽  
Redox Homeostasis ◽  
Immunohistochemical Analysis ◽  
Serum Levels ◽  
Recurrent Event ◽  
Molecular Signature ◽  
Regulatory Subunit ◽  
Proteomic Profiling ◽  
Related Proteins

SummaryThe clinical impact of in-stent thrombosis is high because it is associated with high mortality and 20 % of the patients suffer a recurrent event within the two following years. The aim of this study was to characterise the morphologic and proteomic profile of in-stent thrombi (IST) in comparison to thrombi developed on native coronary arteries (CT) to identify a differential molecular signature. The study included 45 patients with ST-elevation-myocardial-infarction (STEMI) treated by primary-percutaneous-intervention and thrombus aspiration: 21 had IST and 24 had CT. Thrombi were characterised by morphologic immunohistochemical analysis and differential proteomic profiling (2-DE+MALDI-TOF/TOF). Bioinformatic analysis revealed differences in proteins related to oxidative-stress and cell death/survival. IST showed a higher content of structural proteins (gelsolin, actin-cytoplasmic-1, tropomyosin, and myosin) together with an imbalance in redox-homeostasis related proteins (increased superoxide-dismutase and decreased peroxiredoxin-2 thrombus content), and a coordinated increase of chaperones (HSP60 and HSC70) and cellular quality control-related proteins (26S–protease-regulatory-subunit-7). These changes were reflected into a significant decrease in HSC70 systemic levels and a significant increase in advanced-oxidation-protein-products (AOPP) indicative of increased oxidative stress-mediated protein damage in IST. Our results reveal an imbalance in redox-related proteins indicative of an exacerbated oxidative-stress that leads to an accumulation of AOPP serum levels in IST. Moreover, the coordinated increase in chaperones and regulatory proteins reflects the activation of intracellular protection mechanisms to maintain protein integrity in IST. The failure to counterbalance the stress situation could trigger cellular apoptosis leading to the destabilization of the thrombus and to a worse prognosis of IST-STEMI-patients.Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals Dexamethasone enhances the efficacy of atorvastatin in inhibiting excessively inflammation-induced abnormal angiogenesis by regulating macrophages

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Zhitao Gong ◽  
Daqiang Zhan ◽  
Meng Nie ◽  
Xiaochun Li ◽  
Chuang Gao ◽  
...  
Keyword(s):  
Combined Therapy ◽  
Serum Levels ◽  
Chronic Subdural Haematoma ◽  
High Dose ◽  
Serum Samples ◽  
Drug Treatments ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Related Proteins ◽  
First Time

Abstract Background We have recently showed that atorvastatin (ATO) combined with low dose of dexamethasone (DEX) was more efficacious in treating patients with chronic subdural haematoma (CSDH) than ATO monotherapy. This study was designed to investigate the underlying mechanisms of the improved efficacy of this combined therapy. Methods Mass spectrometry was performed to quantitatively detect drugs in haematoma fluids and serum samples from CSDH patients and also in cultured macrophages after treatment with either ATO alone or in combination with DEX. The differentiation and apoptosis of macrophages were evaluated using flow cytometry. The expression of cytokines, chemokines and angiogenesis-related proteins was evaluated using proteome profile arrays, immunoblots and ELISA, respectively. Results ATO was detected in haematoma fluids and serum samples, whose levels were increased significantly in samples collected from patients treated with both ATO and DEX. ATO was also increased in cultured macrophages treated with ATO and DEX. The numbers of M1-polarized macrophages were higher than the M2 phenotype in the haematoma fluids of patients. Cultured macrophages treated with ATO and DEX had reduced numbers of M1-polarized macrophages, increased numbers of M2-polarized macrophages as compared to monotherapies, and decreased rate of apoptosis induced by high-dose DEX. DEX enhanced the anti-inflammatory and anti-angiogenic activity of ATO by suppressing VEGFA and other inflammatory angiogenic factors. Consistent with the finding, patients responded well to the drug treatments had lower serum levels of VEGFA. Conclusions We have shown for the first time that ATO given orally was detected in CSDH haematoma fluids. DEX enhances the anti-inflammatory and anti-angiogenic effects of ATO, primarily by increasing the presence of ATO in haematoma and macrophages and by regulating the functions of macrophages.

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