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.

scholarly journals Secreted Frizzled Related Proteins in Cardiovascular and Metabolic Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Hua Guan ◽  
Jin Zhang ◽  
Jing Luan ◽  
Hao Xu ◽  
Zhenghao Huang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Structural Characteristics ◽  
Wnt Signaling Pathway ◽  
Secreted Protein ◽  
Related Protein ◽  
Disease Biomarkers ◽  
Protein Levels ◽  
Related Proteins

Abnormal gene expression and secreted protein levels are accompanied by extensive pathological changes. Secreted frizzled related protein (SFRP) family members are antagonistic inhibitors of the Wnt signaling pathway, and they were recently found to be involved in the pathogenesis of a variety of metabolic diseases, which has led to extensive interest in SFRPs. Previous reports highlighted the importance of SFRPs in lipid metabolism, obesity, type 2 diabetes mellitus and cardiovascular diseases. In this review, we provide a detailed introduction of SFRPs, including their structural characteristics, receptors, inhibitors, signaling pathways and metabolic disease impacts. In addition to summarizing the pathologies and potential molecular mechanisms associated with SFRPs, this review further suggests the potential future use of SFRPs as disease biomarkers therapeutic targets.

scholarly journals Antioxidant and anti-inflammatory effect of ligustilide on sepsis-induced acute kidney injury via TLR4/NF-κB and Nrf2/HO-1 signaling

2021 ◽  
Vol 20 (1) ◽  
pp. 83-87
Author(s):  
Xiumin Yang ◽  
Chencai Qiao ◽  
Chao Zheng ◽  
Qingjun Deng
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Serum Levels ◽  
Heme Oxygenase 1 ◽  
Protein Levels ◽  
Anti Inflammatory ◽  
Commercial Kits

Purpose: To investigate the protective effect of ligustilide on sepsis-induced acute kidney injury (AKI) and the signaling pathways involved.Methods: Sepsis-induced AKI was established by cecal ligation and puncture (CLP) in mice. Histopathological renal damage was examined using hematoxylin and eosin (H & E) staining while creatinine and cytokines were measured using commercial kits. Protein levels were determined by Western blotting.Results: Vacuoles, dilations, degeneration, and necrosis were observed in CLP mouse kidneys, but these alterations were countered by 20 mg/kg of ligustilide. Serum creatinine, blood urea nitrogen (BUN), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were significantly increased in CLP mice compared with control. Furthermore, the serum levels of these indicators in serum were lowered by ligustilide (p < 0.01). The expression levels of Toll-like receptor 4 (TLR4) TLR4 and phosphorylated nuclear factor (NF)-κB in CLP mice were also downregulated by ligustilide. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels increased in CLP mice, but were attenuated by ligustilide (p < 0.01). Superoxide dismutase (SOD) and glutathione (GSH) levels decreased in CLP mice but were increased by ligustilide (p < 0.01). Increased expression of Nrf2 and heme oxygenase-1 (HO-1) were observed in CLP mice, and were further enhancced by ligustilide.Conclusion: Ligustilide exerts antioxidant and anti-inflammatory effects on sepsis-induced AKI via TLR4/NF-κB and Nrf2/HO-1 signaling pathways. Keywords: Ligustilide, Sepsis, Acute kidney injury, TLR4/NF-κB signaling pathway, Nrf2/HO-1 signaling pathway

IMMUNOLOGICAL REACTIVITY OF INSULIN IN HUMAN SERUM

1966 ◽  
Vol 53 (4) ◽  
pp. 673-680 ◽  
Author(s):  
Torsten Deckert ◽  
Kai R. Jorgensen
Keyword(s):  
Normal Subjects ◽  
The Other ◽  
Human Pancreas ◽  
Porcine Pancreas ◽  
Crystalline Insulin ◽  
Endogenous Insulin ◽  
Significant Difference ◽  
Human Sera ◽  
Normal Human ◽  
The One

ABSTRACT The purpose of this study was to investigate whether a difference could be demonstrated between crystalline insulin extracted from normal human pancreas, and crystalline insulin extracted from bovine and porcine pancreas. Using Hales & Randle's (1963) immunoassay no immunological differences could be demonstrated between human and pig insulin. On the other hand, a significant difference was found, between pig and ox insulin. An attempt was also made to determine whether an immunological difference could be demonstrated between crystalline pig insulin and crystalline human insulin from non diabetic subjects on the one hand and endogenous, circulating insulin from normal subjects, obese subjects and diabetic subjects on the other. No such difference was found. From these experiments it is concluded that endogenous insulin in normal, obese and diabetic human sera is immunologically identical with human, crystalline insulin from non diabetic subjects and crystalline pig insulin.

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

Negative Correlation Between Serum Levels of Homocysteine and Apolipoprotein M

2019 ◽  
Vol 19 (2) ◽  
pp. 120-126
Author(s):  
J. Wei ◽  
Y. Yu ◽  
Y. Feng ◽  
J. Zhang ◽  
Q. Jiang ◽  
...  
Keyword(s):  
Negative Correlation ◽  
Hepg2 Cells ◽  
Serum Levels ◽  
Significant Negative Correlation ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Apolipoprotein M ◽  
Protein Mass ◽  
Protein Levels ◽  
Phosphoinositide 3 Kinase

Background: Homocysteine (Hcy) has been suggested as an independent risk factor for atherosclerosis. Apolipoprotein M (apoM) is a constituent of the HDL particles. The goal of this study was to examine the serum levels of homocysteine and apoM and to determine whether homocysteine influences apoM synthesis. Methods: Serum levels of apoM and Hcy in 17 hyperhomocysteinemia (HHcy) patients and 19 controls were measured and their correlations were analyzed. Different concentrations of homocysteine (Hcy) and LY294002, a specific phosphoinositide 3- kinase (PI3K) inhibitor, were used to treat HepG2 cells. The mRNA levels were determined by RT-PCR and the apoM protein mass was measured by western blot. Results: We found that decreased serum apoM levels corresponded with serum HDL levels in HHcy patients, while the serum apoM levels showed a statistically significant negative correlation with the serum Hcy levels. Moreover, apoM mRNA and protein levels were significantly decreased after the administration of Hcy in HepG2 cells, and this effect could be abolished by addition of LY294002. Conclusions: resent study demonstrates that Hcy downregulates the expression of apoM by mechanisms involving the PI3K signal pathway.

Brain-derived neurotrophic factor is associated with coronary macrophage infiltrates in patients with acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R.A Montone ◽  
M Camilli ◽  
M Russo ◽  
M Del Buono ◽  
F Gurguglione ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Neurotrophic Factor ◽  
Serum Levels ◽  
Brain Derived Neurotrophic Factor ◽  
C Reactive Protein ◽  
St Segment Elevation ◽  
Protein Levels ◽  
Reactive Protein ◽  
Coronary Syndrome ◽  
St Segment

Abstract Background Brain-derived neurotrophic factor (BDNF) is a neurotrophine that plays a key role in the regulation of both central and peripheral nervous system. Moreover, BDNF is secreted in multiple tissues and exerts systemic, autocrine, and paracrine effects in the cardiovascular system. Of importance, BDNF expression was enhanced in macrophages and smooth muscle cells in atherosclerotic coronary arteries and may be involved in thrombus formation. Thus, BDNF has been suggested as an important link between inflammation and thrombosis, potentially involved in the pathogenesis of acute coronary syndrome (ACS). Purpose In our study we aimed at assessing serum levels of BDNF in patients with ACS, evaluating differences according to clinical presentation [ST-segment elevation myocardial infarction (STEMI) vs. Non-ST-segment elevation ACS (NSTE-ACS)]. Moreover, we assessed the presence of optical coherence (OCT)-defined macrophage infiltrates (MØI) in the culprit vessel of ACS patients and evaluated their relationship with BDNF levels. Methods ACS patients were prospectively selected. Blood samples were collected at admission and serum levels of BDNF were subsequently assessed. Presence of OCT-defined MØI along the culprit vessel was assessed. Results 166 ACS patients were enrolled [mean age 65.3±11.9 years, 125 (75.3%) male, 109 STEMI, 57 NSTE-ACS]. Serum levels of BDNF were higher among STEMI patients compared with NSTE-ACS [median (IQR) 2.48 pg/mL (1.54–3.34) vs. 2.12 pg/mL (1.34–2.47), p=0.007], while C-reactive protein levels did not differ between the two groups. OCT assessment was performed in 53 patients and MØI were detected in 27 patients. Of importance, patients with MØI in the culprit vessel had higher levels of BDNF compared with patients without MØI [median (IQR) 2.23 pg/mL (1.38–2.53) vs. 1.41 pg/mL (0.93–2.07), p=0.023], while C-reactive protein levels did not differ between the two groups. Of note, at multivariate regression analysis BDNF levels were independent predictor of MØI [OR: 2.20; 95% CI (1.02–4.74), p=0.043]. Conclusions Serum levels of BDNF may reliable identify the presence of local macrophage inflammatory infiltrates in patients with ACS. Moreover, BDNF levels are higher in patients with STEMI compared with NSTE-ACS. Taken together, these data suggest that BDNF may represent an interesting link between local inflammatory activation and enhanced thrombosis in ACS. BDNF serum levels Funding Acknowledgement Type of funding source: None

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 miR-146a-5p Promotes Chondrocyte Apoptosis and Inhibits Autophagy of Osteoarthritis by Targeting NUMB

Cartilage ◽  
2021 ◽  
pp. 194760352110235
Author(s):  
Hongjun Zhang ◽  
Wendi Zheng ◽  
Du Li ◽  
Jia Zheng
Keyword(s):  
Caspase 3 ◽  
Cartilage Tissue ◽  
Luciferase Reporter ◽  
Chondrocyte Apoptosis ◽  
Knee Cartilage ◽  
Before And After ◽  
Related Proteins ◽  
Human And Mouse

Objective miR-146a-5p was found to be significantly upregulated in cartilage tissue of patients with osteoarthritis (OA). NUMB was shown to be involved in the autophagy regulation process of cells. We aimed to learn whether NUMB was involved in the apoptosis or autophagy process of chondrocytes in OA and related with miR-146a-5p. Methods QRT-PCR was used to detect miR-146a-5p level in 22 OA cartilage tissues and 22 controls. The targets of miR-146a-5p were analyzed using software and the luciferase reporter experiment. The apoptosis and autophagy, and related proteins were detected in chondrocytes treated with miR-146a-5p mimic/inhibitor or pcDNA3.1-NUMB/si-NUMB and IL-1β, respectively. In vivo experiment, intra-articular injection of miR-146a-5p antagomir/NC was administered at the knee of OA male mice before and after model construction. Chondrocyte apoptosis and the expression of apoptosis and autophagy-related proteins were also detected. Results miR-146a-5p was highly expressed in knee cartilage tissue of patients with OA, while NUMB was lowly expressed and negatively regulated by miR-146a-5p. Upregulation of miR-146a-5p can promote cell apoptosis and reduce autophagy of human and mouse chondrocytes by modulating the levels of cleaved caspase-3, cleaved PARP, Bax, Beclin 1, ATG5, p62, LC3-I, and LC3-II. Increasing the low level of NUMB reversed the effects of miR-146a-5p on chondrocyte apoptosis and autophagy. Intra-articular injection of miR-146a-5p antagomir can also reverse the effects of miR-146a-5p on the apoptosis and autophagy of knee joint chondrocytes in OA mice. Conclusion Downregulation of miR-146a-5p suppresses the apoptosis and promotes autophagy of chondrocytes by targeting NUMB in vivo and in vitro.

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.

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