AST-120, an Oral Carbon Absorbent, Protects against the Progression of Atherosclerosis in a Mouse Chronic Renal Failure Model by Preserving sFlt-1 Expression Levels

Abstract Soluble Flt-1 (sFlt-1), an endogenous antagonist of the proatherogenic cytokine placental growth factor, is decreased in chronic kidney disease (CKD), leading to atherosclerotic progression. In this study, we investigated the effect of AST-120, an oral carbon adsorbent which can remove uremic toxins, on sFlt-1 expression levels and atherosclerosis progression. Atherosclerotic apolipoprotein E-deficient mice underwent a 5/6 nephrectomy (5/6 NR) or a sham operation (sham) at 8 weeks of age and were then treated or not with oral AST-120 for 12 weeks. sFlt-1 expression levels and the degree of atherosclerosis were assessed at 22 weeks of age in each of the four groups (sham; n = 7, 5/6 NR; n = 10, sham + AST-120: n = 8, 5/6 NR + AST-120; n = 8). The expression levels of sFlt-1 mRNA in the kidney were significantly lower in the 5/6 NR group than in the sham group, but AST-120 treatment prevented this decrease in sFlt-1 levels. Similarly, the atherosclerotic plaque area of the thoracoabdominal aorta was significantly larger in the 5/6 NR group than in the sham group, and AST-120 treatment prevented this increase in atherosclerosis. AST-120 could, therefore, be used as a therapeutic to treat atherosclerosis in patients with CKD.

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Effects of Ozone on Hippocampus BDNF and Fos Expressions in Rats with Chronic Compression of Dorsal Root Ganglia

BioMed Research International ◽

10.1155/2021/5572915 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Lingling Zhu ◽

Yanxiu Wang ◽

Xiaowen Lin ◽

Xu Zhao ◽

Zhi jian Fu

Keyword(s):

Dorsal Root Ganglia ◽

Dorsal Root ◽

Sham Group ◽

Sham Operation ◽

Sprague Dawley ◽

Expression Levels ◽

Fos Protein ◽

Before And After ◽

Formula Group ◽

Fos Expression

The effects of ozone on hippocampal expression levels of brain-derived neurotrophic factor (BDNF) and c-fos protein (Fos) were evaluated in rats with chronic compression of dorsal root ganglia (CCD). Forty-eight adult female Sprague-Dawley rats were randomly divided into the following 4 groups ( n = 12 ): sham operation (sham group), CCD group, CCD with 20 μg/ml of ozone ( CCD + A O 3 group), and CCD with 40 μg/ml of ozone ( CCD + B O 3 group). Except the sham group, unilateral L5 dorsal root ganglion (DRG) compression was performed on all other groups. On days 1, 2, and 4 after the operation, the CCD + A O 3 and CCD + B O 3 groups were injected with 100 μl of ozone with concentrations of 20 and 40 μg/ml, respectively. Thermal withdrawal latencies (TWLs) and mechanical withdrawal thresholds (MWTs) were measured at various time points before and after the operation. BDNF and Fos expressions were examined in the extracted hippocampi using immunohistochemistry. The TWLs and MWTs of CCD model rats that received ozone were lower with decreased BDNF and increased Fos expression levels, on day 21 after the operation, compared to those of the sham group ( P < 0.05 ). The TWLs and MWTs of the CCD + A O 3 and CCD + B O 3 groups were higher with increased BDNF and decreased Fos expression levels, on day 21 after the operation, compared to those of the CCD group ( P < 0.05 ). The TWLs were longer and the MWTs were higher in the CCD + B O 3 group at each time point with increased BDNF and decreased Fos expression levels, on day 21 after the operation, compared to those of the CCD + A O 3 group ( P < 0.05 ). Our results revealed that ozone can relieve the neuropathic pain caused by the pathological neuralgia resulting from DRG compression in rats. The mechanism of action for ozone is likely associated with changes in BDNF and Fos expression levels in the hippocampus.

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The Deleterious Influence of Tenofovir-Based Therapies on the Progression of Atherosclerosis in HIV-Infected Patients

Mediators of Inflammation ◽

10.1155/2012/372305 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Gerard Aragonès ◽

Pedro Pardo-Reche ◽

Laura Fernández-Sender ◽

Anna Rull ◽

Raúl Beltrán-Debón ◽

...

Keyword(s):

Subclinical Atherosclerosis ◽

Plasma Concentrations ◽

Hdl Cholesterol ◽

Lower Plasma ◽

Expression Levels ◽

Inflammatory Biomarker ◽

Atherosclerosis Progression ◽

Cholesterol Levels ◽

Circulating Levels ◽

Progression Of Atherosclerosis

We investigated the potential differential effects of antiretroviral therapies on unbalanced chemokine homeostasis and on the progression of atherosclerosis in HIV-infected patients. A two-year prospective study was performed in 67 consecutive HIV-infected patients initiating antiretroviral therapy with abacavir/lamivudine or tenofovir/emtricitabine. Circulating levels of inflammatory biomarkers, progression of subclinical atherosclerosis and expression levels of selected chemokines genes in circulating leukocytes were assessed. Control subjects showed significantly lower plasma concentrations of CRP, tPA, IL-6, and MCP-1 than HIV-infected patients at a baseline. After two years of followup, the observed decreases in plasma inflammatory biomarker levels were only significant for MCP-1, tPA, and IL-6. The decrease in plasma MCP-1 concentration was associated with the progression of atherosclerosis, and this effect was negligible only in patients receiving TDF-based therapy. Multivariate analysis confirmed that treatment with TDF was positively and significantly associated with a higher likelihood of subclinical atherosclerosis progression. However, the expression levels of selected genes in blood cells only showed associations with the viral load and total and HDL-cholesterol levels. Current antiretroviral treatments may partially attenuate the influence of HIV infection on certain inflammatory pathways, though patients receiving TDF therapy must be carefully monitored with respect to the presence and/or progression of atherosclerosis.

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Plasminogen Activator Inhibitor 1 Deficiency Reduces the Progression of Atherosclerosis in a Murine Model of Human Familial Hypercholesterolemia.

Blood ◽

10.1182/blood.v108.11.1804.1804 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1804-1804

Author(s):

Takayuki Iwaki ◽

Ploplis A. Victoria ◽

Francis J. Castellino

Keyword(s):

Plasminogen Activator Inhibitor ◽

Cell Types ◽

Cellular Functions ◽

Plasminogen Activator Inhibitor 1 ◽

Aortic Sinus ◽

Atherosclerosis Progression ◽

Plaque Area ◽

And Migration ◽

Progression Of Atherosclerosis ◽

Pai 1

Abstract Atherosclerosis has been described as a “self-perpetuating” inflammatory disease which progresses in discrete stages and involves a number of cell types and effector molecules. Lipid metabolic disorders are heavily involved in the genesis and progression of atherosclerosis in humans, and thrombotic complications substantially contribute to the coronary artery disease that frequently accompanies atherosclerosis. A relevant mouse model of human atherosclerosis with elevated LDL-cholesterol (C) is one in which both the Ldlr and Apobec1 genes are deleted (Ldlr−/−/Apobec1−/−), since these mice lack the ability to convert apoB-100 to apoB-48 in liver and also are defective in LDL clearance. We have generated Ldlr−/−/Apobec1−/−/PAI-1−/−and characterized atherosclerosis progression in these mice. VLDL, LDL, HDL, and total C levels were identical between Ldlr−/−/Apobec1−/−and Ldlr−/−/Apobec1−/−/PAI-1−/−mice (VLDL-C; 30.3±1.8 vs 26.0±1.7 (mg/dl), LDL-C; 268.7±6.3 vs 274.1±13.1 (mg/dl), HDL-C; Total-C; 353.8±8.1 vs 356.8±14.5 (mg/dl), respectively). However, both the plaque size in the aortic sinus and the extent of plaque area in aorta were significantly smaller in Ldlr−/−/Apobec1−/−/PAI-1−/−mice relative to Ldlr−/−/Apobec1−/−mice (plaque in aortic sinus; 158792.9±11958.2 vs 227243.5±15291.1 (μm2), plaque area in aorta; 3.90±0.34 vs 5.10±0.27 (%), respectively). To elucidate the cellular functions, especially macrophages, in the plaque, bone marrow-derived macrophages (BMMs) were isolated and utilized for Dil-oxidized (Ox) LDL uptake assays and migration assays using 8 μm pore culture inserts. There were no significant differences in Dil-OxLDL uptake by BMMs between the two genotypes. The kinetics of migration of BMMs was more rapid in Ldlr−/−/Apobec1−/−/PAI-1−/−cells than Ldlr−/−/Apobec1−/−cells. Furthermore, thioglycollate-induced intraperitoneal migration of macrophages was increased in Ldlr−/−/Apobec1−/−/PAI-1−/−mice vs Ldlr−/−/Apobec1−/−mice. Results from these studies indicate that cell migratory differences may contribute to attenuating atheroma formation in a PAI-1 deficient state.

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Progression of atherosclerosis in ApoE-deficient mice that express distinct molecular forms of TNF-alpha

The Journal of Pathology ◽

10.1002/path.2305 ◽

2008 ◽

Vol 214 (5) ◽

pp. 574-583 ◽

Cited By ~ 24

Author(s):

M Canault ◽

F Peiretti ◽

M Poggi ◽

C Mueller ◽

F Kopp ◽

...

Keyword(s):

Molecular Forms ◽

Tnf Alpha ◽

Deficient Mice ◽

Progression Of Atherosclerosis

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Quantification of plaque area and characterization of plaque biochemical composition with atherosclerosis progression in ApoE/LDLR−/− mice by FT-IR imaging

The Analyst ◽

10.1039/c3an01050c ◽

2013 ◽

Vol 138 (21) ◽

pp. 6645 ◽

Cited By ~ 20

Author(s):

Tomasz P. Wrobel ◽

Lukasz Mateuszuk ◽

Renata B. Kostogrys ◽

Stefan Chlopicki ◽

Malgorzata Baranska

Keyword(s):

Biochemical Composition ◽

Atherosclerosis Progression ◽

Plaque Area ◽

Ir Imaging ◽

Ft Ir

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SPACIA1/SAAL1 Deletion Results in a Moderate Delay in Collagen-Induced Arthritis Activity, along with mRNA Decay of Cyclin-dependent Kinase 6 Gene

International Journal of Molecular Sciences ◽

10.3390/ijms19123828 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3828

Author(s):

Ryoji Fujii ◽

Rie Komatsu ◽

Tomoo Sato ◽

Iwao Seki ◽

Koji Konomi ◽

...

Keyword(s):

Severe Disease ◽

Critical Factor ◽

Synovial Fibroblasts ◽

Transcriptional Level ◽

Cyclin Dependent Kinase ◽

Collagen Induced Arthritis ◽

Expression Levels ◽

Amyloid A ◽

Interfering Rna ◽

Deficient Mice

This study was performed to elucidate the molecular function of the synoviocyte proliferation-associated in collagen-induced arthritis (CIA) 1/serum amyloid A-like 1 (SPACIA1/SAAL1) in mice CIA, an animal model of rheumatoid arthritis (RA), and human RA-synovial fibroblasts (RASFs). SPACIA1/SAAL1-deficient mice were generated and used to create mouse models of CIA in mild or severe disease conditions. Cell cycle-related genes, whose expression levels were affected by SPACIA1/SAAL1 small interfering RNA (siRNA), were screened. Transcriptional and post-transcriptional effects of SPACIA1/SAAL1 siRNA on cyclin-dependent kinase (cdk) 6 gene expression were investigated in human RASFs. SPACIA1/SAAL1-deficient mice showed later onset and slower progression of CIA than wild-type mice in severe disease conditions, but not in mild conditions. Expression levels of cdk6, but not cdk4, which are D-type cyclin partners, were downregulated by SPACIA1/SAAL1 siRNA at the post-transcriptional level. The exacerbation of CIA depends on SPACIA1/SAAL1 expression, although CIA also progresses slowly in the absence of SPACIA1/SAAL1. The CDK6, expression of which is up-regulated by the SPACIA1/SAAL1 expression, might be a critical factor in the exacerbation of CIA.

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Sequential testicular atrophy involves changes in cellular proliferation and apoptosis associated with variations in aromatase P450 expression levels in Irs-2-deficient mice

Journal of Anatomy ◽

10.1111/joa.12917 ◽

2018 ◽

Vol 234 (2) ◽

pp. 227-243

Author(s):

Leonardo Catalano-Iniesta ◽

Virginia Sánchez-Robledo ◽

Maria Carmen Iglesias-Osma ◽

Maria José García-Barrado ◽

Marta Carretero-Hernández ◽

...

Keyword(s):

Cellular Proliferation ◽

Testicular Atrophy ◽

Expression Levels ◽

Proliferation And Apoptosis ◽

P450 Expression ◽

Deficient Mice

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Effect and Mechanism of Lidocaine Pretreatment Combined with Dexmedetomidine on Oxidative Stress in Patients with Intracranial Aneurysm Clipping

Journal of Healthcare Engineering ◽

10.1155/2021/4293900 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Junting Zhang ◽

Hongwei Zhang ◽

Liang Zhao ◽

Zhanqi Zhao ◽

Ying Liu

Keyword(s):

Oxidative Stress ◽

Intracranial Aneurysm ◽

Brain Tissue ◽

Sham Group ◽

Drug Group ◽

Sham Operation ◽

Lidocaine Group ◽

Aneurysm Clipping ◽

Single Drug ◽

Lidocaine Pretreatment

This study aimed to explore the effect and mechanism of lidocaine pretreatment combined with dexmedetomidine on oxidative stress in patients with intracranial aneurysm clipping. Many studies have used various drugs such as lidocaine to explore the effect and mechanism of lidocaine pretreatment. A total of 80 patients with intracranial aneurysm clipping surgery were randomly divided into 4 groups: the single lidocaine group, single dexmedetomidine group, lidocaine combined with dexmedetomidine group, and control group. The thread embolism method was used to establish a stable intracranial aneurysm model of Hashimoto rats. Fifty adult rats were randomly divided into a sham operation group, ligation of the left common carotid artery and bilateral posterior branch of renal artery, lidocaine group, dexmedetomidine group, and lidocaine combined with dexmedetomidine group. The colorimetric method was used to determine the oxidative stress indicators in brain tissue: MDA content, SOD activity, and T-AOC content. The western blot method characterized the protein levels related to oxidative stress: nNOS, iNOS, and NADPH oxidase subunits p22phox, gp91phox, and p47phox. The differences in each index between the groups were statistically significant ( P < 0.05 ). Animal experiment results revealed that the content of MDA in the brain tissue of rats in the LD group was significantly lower than that in the single-drug group and sham group. The T-AOC and SOD concentrations in the LD group were significantly higher than those in the single-drug group and sham group, and the differences between the groups were statistically significant ( P < 0.05 ). The protein expression of the LD group was significantly lower than that of the drug-alone group and model group, and the difference between groups was statistically significant ( P < 0.05 ). To sum up, lidocaine pretreatment combined with dexmedetomidine can effectively maintain the hemodynamic stability of patients with intracranial aneurysm clipping and reduce postoperative oxidative stress response. Its mechanism of action may be related to the inhibition of oxidative stress damage mediated by nNOS, iNOS, and p22phox, gp91phox, and p47phox in the hippocampus. Our study has significant and applicable medical aspects in lidocaine pretreatment combined with dexmedetomidine on oxidative stress in patients.

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Exendin-4 improves neuron protection and functional recovery in experimental spinal cord injury in rats through regulating PCBP2 expression

10.1101/2020.11.09.373993 ◽

2020 ◽

Author(s):

Huaichao Luo ◽

Qingwei Wang ◽

Lei Wang

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Cell Apoptosis ◽

Sham Group ◽

Sham Operation ◽

Therapeutic Effects ◽

Rat Models ◽

Apoptosis Rate ◽

Cord Injury ◽

Group A

AbstractAimsIn the present research, we assessed the therapeutic effects of Exendin-4 (Ex-4) on rat models with spinal cord injury (SCI).Materials and methods36 male Sprague–Dawley rats were randomly allocated into three groups, including sham operation group, SCI group and SCI+Ex-4 group (Ex-4 treatment (10 µg/rat) after SCI, i.p.). In the SCI group, a laminectomy was performed at the T10 vertebrae, followed by weight-drop contusion of the spinal cord. In the sham group, a laminectomy was carried out without SCI contusion.Key findingsOur results showed that Basso-Beattie-Bresnahan scale scores were significantly decreased after SCI, and were obviously improved in SCI rats with Ex-4 administration. Additionally, the water content of spinal cord in SCI group was dramatically increased than that in sham group, and after Ex-4 treatment, degree of edema of spinal cord was remarkably reduced. And also, concentration levels of inflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α) in the spinal cord were significantly elevated after SCI, and were remarkably reduced in SCI rats with Ex-4 administration. Subsequently, cell apoptosis rate in the injured spinal cord was significantly increased, and after Ex-4 treatment, cell apoptosis rate was remarkably decreased. We also revealed that levels of PCBP2 mRNA and protein were significantly up-regulated after SCI, and were dramatically dropped in SCI rats with Ex-4 administration.SignificanceTake altogether, our findings disclosed that Ex-4 plays a role in promoting neurological function recovery and inhibiting neuronal apoptosis through effecting PCBP2 expression in SCI rat models.

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