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1.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 52(4): 526-530, 2023 Aug 25.
Article in English, Chinese | MEDLINE | ID: mdl-37643986

ABSTRACT

Desensitization therapy for iodinated contrast media (ICM) aims to induce drug tolerance in patients with a history of severe allergic reactions to ICM in a short time. Currently, there is no widely accepted consensus on inducing desensitization to avoid severe allergic responses to ICM. The clinically successful cases have shown that prophylactic use of antihistamines and glucocorticoids can increase the desensitization effect; repeatedly desensitizing and gradually increasing the dose can be conducive to establishing better tolerance to ICM. Most desensitization effects, including stress resistance, can endure 24-48 h. The mechanisms of desensitization therapy remain unclear, the initial dose, administration interval and dose gradient are largely based on clinical experiences and the reaction of patients. This article reviews the current research progress on ICM-related allergies, desensitization methods and related mechanisms, as well as the benefits and hazards of desensitization, to provide a reference for desensitization treatment of hypersensitivity to ICM .


Subject(s)
Contrast Media , Hypersensitivity , Humans , Contrast Media/adverse effects , Consensus , Glucocorticoids
2.
Ren Fail ; 45(1): 2199093, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37051660

ABSTRACT

PURPOSE: This cohort study was designed to explore whether roxadustat or erythropoietin could affect thyroid function in patients with renal anemia. METHODS: The study involved 110 patients with renal anemia. Thyroid profile and baseline investigations were carried out for each patient. The patients were divided into two groups: 60 patients taking erythropoietin served as the control group (rHuEPO group) and 50 patients using roxadustat served as the experimental group (roxadustat group). RESULTS: The results indicated that there were no significant differences in serum total thyroxine (TT4), total triiodothyronine (TT3), free triiodothyronine (FT3), free thyroxine (FT4) or thyroid stimulating hormone (TSH) between the two groups at baseline. After treatment, TSH, FT3, and FT4 were significantly lower in the roxadustat group than in the rHuEPO group (p < 0.05). After adjusting for age, sex, dialysis modality, thyroid nodules and causes of kidney disease, Cox regression showed that roxadustat was an independent influencing factor on thyroid dysfunction (HR 3.37; 95% CI 1.94-5.87; p < 0.001). After 12 months of follow-up, the incidence of thyroid dysfunction was higher in the roxadustat group than in the rHuEPO group (log-rank p < 0.001). CONCLUSION: Roxadustat may lead to a higher risk of thyroid dysfunction, including low TSH, FT3 and FT4, than rHuEPO in patients with renal anemia.


Subject(s)
Anemia , Erythropoietin , Kidney Diseases , Humans , Triiodothyronine , Thyroxine/therapeutic use , Thyroid Gland , Cohort Studies , Thyrotropin , Chronic Disease , Epoetin Alfa , Anemia/drug therapy , Anemia/etiology
3.
Altern Ther Health Med ; 29(3): 153-159, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36735716

ABSTRACT

Context: Hepatitis B can develop into cirrhosis, and most liver cancers evolve on the basis of chronic hepatitis and cirrhosis. Many patients are already at an advanced stage when diagnosed. In recent years, clinicians have advocated detection of liver cancer using multiple markers in combination to improve the sensitivity and specificity of testing. Objective: The study aimed to evaluate the clinical value of using four tumor indicators-urea, alpha L-fucosidase (AFU), carbohydrate antigen 153 (CA153), carbohydrate antigen 125 (CA125), and alpha fetoprotein (AFP) and comparing the use of combined indicators to use of a single indicator for the diagnosis of liver cancer. Design: The research team performed a prospective study. Setting: The study took place at Clinical Laboratory, Baoding People's Hospital, Baoding City, Hebei Province, China. Participants: Participants were 98 patients with chronic hepatitis B, who became the CHB group; 102 patients with liver cirrhosis, who became the cirrhosis group, and 100 patients with liver cancer, who became the liver cancer group. They all had been admitted to the hospital between March 2019 and March 2021. Outcome Measures: The research team measured the urea, AFU, CA153, CA125, and AFP levels of the three groups, constructed an ROC curve, and analyzed the diagnostic values of the indicators singly and in combination for liver cancer. Results: For the levels of urea, AFU, CA153, CA125, and AFP, the CHB group's levels were significantly lower than those of the cirrhosis and liver cancer groups (both P < .001), and the cirrhosis group's levels were significantly lower than those of the liver cancer group (P < .001). In the CHB group, the compensatory group's levels were significantly lower than those of the decompensated group (P < .05). In the cirrhosis group, no significant differences existed between the levels of the grade A and grade B groups (P < .001), between those of the grade A and grade C groups (P < .001), or between those of the grade B and grade C groups (P < .001). In the cirrhosis group, the levels of the no ascites group were significantly lower than those of the ascites group (P < .05). In the liver cancer group, the levels of the stage I-II group were significantly lower than those of the stage III and stage IV groups (both P < .05), and those of the stage IV group were significantly lower than those of the stage Ⅳ group (P < .05). The levels of the <5cm group were significantly lower than those of the ≥5cm group (P < .001). The value of using a combination of indicators for diagnosis was significantly higher than that of a single indicator (P < .001). Conclusions: Urea, AFU, CA153, CA125, and AFP all have diagnostic value in the evaluation of chronic hepatitis B-cirrhosis and liver cancer, with the highest efficacy, sensitivity and specificity from a combined test and diagnosis.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B, Chronic , Liver Neoplasms , Humans , alpha-Fetoproteins , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/diagnosis , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/pathology , Prospective Studies , Liver Neoplasms/diagnosis , Liver Neoplasms/pathology , Liver Cirrhosis/diagnosis , Biomarkers, Tumor , Carbohydrates
4.
Ir J Med Sci ; 192(6): 3187-3194, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36826711

ABSTRACT

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates inflammatory response and CD4+ T cell differentiation in autoimmune diseases, while its clinical role in rheumatoid arthritis (RA) lacks sufficient evidence. Subsequently, this study intended to explore the vertical change of PCSK9, and its linkage with T helper (Th) cells, regulatory T (Treg) cells, clinical features, and treatment outcomes in RA patients. METHODS: This multi-center, prospective, cohort study determined serum PCSK9 in 89 RA patients who received conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and 50 healthy controls (HCs) after recruitment by enzyme-linked immunosorbent assay. For RA patients, serum PCSK9 was also determined at 6th week, 12th week, and 24th week; meanwhile, Th1, Th2, Th17, and Treg cells at baseline were determined through flow cytometry. RESULTS: PCSK9 was increased in RA patients compared to HCs (median: 209.2 versus 122.0 ng/mL, P < 0.001). In RA patients, PCSK9 positively correlated with Th17 cells (P = 0.023) and Th17/Treg ratio (P = 0.018), but did not link with Th1 cells, Th2 cells, Th1/Th2 ratio, or Treg cells. Meanwhile, PCSK9 was not associated with any demographics and medication histories, while it positively correlated with C-reactive protein (P = 0.010), disease activity score in 28 joints (P = 0.009), physician's global assessment (P = 0.015), and clinical disease activity index (P = 0.040). Importantly, PCSK9 gradually reduced from baseline to 24th week; its decrement related to higher possibility of treatment response (P = 0.002), low disease activity (P = 0.001), and remission of csDMARDs (P = 0.012). CONCLUSION: Circulating PCSK9 shows the potency as a biomarker for disease management and treatment outcome prediction of csDMARDs in RA.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Humans , Th17 Cells/metabolism , Proprotein Convertase 9/therapeutic use , T-Lymphocytes, Regulatory , Cohort Studies , Prospective Studies , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/metabolism , Antirheumatic Agents/therapeutic use , Treatment Outcome
5.
Entropy (Basel) ; 24(8)2022 Jul 31.
Article in English | MEDLINE | ID: mdl-36010721

ABSTRACT

The problem addressed by dictionary learning (DL) is the representation of data as a sparse linear combination of columns of a matrix called dictionary. Both the dictionary and the sparse representations are learned from the data. We show how DL can be employed in the imputation of multivariate time series. We use a structured dictionary, which is comprised of one block for each time series and a common block for all the time series. The size of each block and the sparsity level of the representation are selected by using information theoretic criteria. The objective function used in learning is designed to minimize either the sum of the squared errors or the sum of the magnitudes of the errors. We propose dimensionality reduction techniques for the case of high-dimensional time series. For demonstrating how the new algorithms can be used in practical applications, we conduct a large set of experiments on five real-life data sets. The missing data (MD) are simulated according to various scenarios where both the percentage of MD and the length of the sequences of MD are considered. This allows us to identify the situations in which the novel DL-based methods are superior to the existing methods.

6.
Pak J Med Sci ; 38(5): 1343-1348, 2022.
Article in English | MEDLINE | ID: mdl-35799733

ABSTRACT

Objectives: To investigate the clinical value of contrast-enhanced CT combined with PET/CT in the differential diagnosis of mediastinal lymph node metastasis (MLNM) of non-small-cell lung cancer (NSCLC). Methods: A total of 120 patients with NSCLC combined with mediastinal lymphadenopathy hospitalized in our hospital were selected. All the patients received radical resection of lung cancer and mediastinal lymphadenectomy. After pathological diagnosis, they were divided into MLNM group (malignant group, undergoing contrast-enhanced CT) and non-MLNM group (benign group, receiving contrast-enhanced CT combined with PET-CT). The results were judged by two senior radiologists independently. The results of different scanning methods and postoperative pathology were compared using the t test, χ2 test and Pearson correlation coefficient test. Results: Compared with the pathological results, contrast-enhanced CT diagnosed 31 cases, with a coincidence rate of 62%, and contrast-enhanced CT combined with PET-CT diagnosed 42 cases, with a coincidence rate of 84%, presenting a statistically significant difference (P = 0.02). Among the 120 patients with lung cancer, pathological examination confirmed MLNM in 50 patients and benign enlargement in 70 patients, contrast-enhanced CT alone detected metastasis in 40 patients and benign enlargement in 80 patients, and contrast-enhanced CT combined with PET-CT detected metastasis in 47 patients and benign enlargement in 73 patients. The sensitivity and accuracy of the latter were significantly higher than those of the former (sensitivity, P = 0.01; accuracy, P = 0.01). With the increase in the malignancy of lymph nodes, the degree of CT enhancement, the concentration of radioactive substances and SUV value increased, showing positive correlations. Conclusion: Contrast-enhanced CT combined with PET/CT in the diagnosis of MLNM of NSCLC presents higher coincidence rate, sensitivity and accuracy. With the increase in tumor malignancy, the enhancement degree and radioactive substance concentration increase. The two methods are synergistic and complementary in diagnosing MLNM.

7.
Materials (Basel) ; 15(5)2022 Mar 07.
Article in English | MEDLINE | ID: mdl-35269208

ABSTRACT

The application of tunnel-slag-improved high liquid limit soil as filling materials in subgrade is a green environmental technology. This study explored the influence of tunnel slag mixing on the physical and mechanical properties of improved soils, based on the engineering background of Liyu highway, Guangxi Province, China. Firstly, the optimal moisture content, maximum dry density, shear strength parameters, California bearing ratio (CBR) and resilience modulus of plain and tunnel-slag-improved high liquid limit soils were experimentally determined. Results showed that the direct utilization of untreated soil was unacceptable in subgrade practice. A significant enhancement of integrity of high liquid limit soils could be obtained by tunnel slag mixing, and the value of 15% was determined as the optimal tunnel slag content in soils, leading to improved soil performance meeting the specification requirements. Then, numerical simulation on the stability of subgrade slope of tunnel-slag-improved soils at the content of 15% was conducted. It also reported the long-term subgrade settlements. The feasibility of utilization of tunnel slag in improving properties of high liquid limit soils was further validated. Finally, a good application of tunnel-slag-improved high liquid limit soil as subgrade filling materials in Liyu highway was achieved. The findings in this study could provide useful guidance for similar engineering.

9.
Materials (Basel) ; 15(1)2022 Jan 05.
Article in English | MEDLINE | ID: mdl-35009536

ABSTRACT

Shotcrete lining shows high resistance but extremely low deformability. The utilization of yielding elements in shotcrete lining, which leads to the so-called ductile lining, provides a good solution to cope with tunnel squeezing deformations. Although ductile lining exhibits great advantages regarding tunnel squeezing deformation control, little information has been comprehensively and systematically available for its mechanism and design. This is a review paper for the purpose of summarizing the development history and discussing the state of the art of ductile lining. It begins by providing a brief introduction of ductile lining and an explanation of the importance of studying this issue. A following summary of supporting mechanism and benefits of ductile lining used in tunnels excavated in squeezing ground conditions is provided. Then, it summarizes the four main types of yielding elements applied in shotcrete lining and introduces their basic structures and mechanical performances. The influences of parameters of yielding elements on the supporting effect are discussed and the design methods for ductile lining are reviewed as well. Furthermore, recommendations for further research in ductile lining are proposed. Finally, a brief summary is presented.

11.
Environ Sci Pollut Res Int ; 29(16): 23094-23103, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34796441

ABSTRACT

The superior photocatalytic activity of semiconductor-based photocatalytic materials has attracted great attention. In this work, a series of novel Ag3PO4/g-C3N4-x (APO/CNx) composites with the Z-scheme structure were fabricated through a facile precipitation method. B naphthol, a typical phenolic compound, was selected to evaluate the photocatalytic activity of all as-prepared photocatalysts. The obtained APO/CNx composites exhibited excellent photocatalytic activity for degradation of B naphthol under visible-light irradiation. Experimental results showed that the degradation rate toward B naphthol could reach to 90.5% for 180 min, which was almost 3.66 times higher than pure g-C3N4, indicating that the presence of nitrogen vacancies and Z-scheme structure could efficiently improve the photocatalytic performance of pure g-C3N4. Furthermore, the results of trapping experiments and electron spin resonance (ESR) spectroscopy manifest that •O2- and •OH radicals were the predominant active substances for B naphthol degradation, and the possible mechanism of improved photocatalytic performance was elucidated. This work will provide an innovative perspective for constructing Z-scheme photocatalysts for the application of photocatalytic in the field of wastewater treatment.

12.
Behav Brain Res ; 414: 113486, 2021 09 24.
Article in English | MEDLINE | ID: mdl-34302872

ABSTRACT

Depression is a common psychiatric disorder that can occur throughout an individual's lifespan. Chronic unpredictable mild stress (CUMS) protocol is currently the most commonly used to develop an animal model of depression. Due to the variable duration and procedure of CUMS, it is difficult to reproduce and explore the mechanism of CUMS-induced depression effectively. In the present study, the CUMS-induced behavioral phenotypes were assessed in male C57BL/6J mice at the age of 9-18 weeks. The mice stressed for 3-8 weeks exhibited lower body weight as well as longer immobility time of forced swim and tail suspension test compared to control mice. Moreover, lessening and impairment of hippocampal neurons was found in stressed mice at the age of 18 weeks, which was correlated with increased relative mRNA expression levels of inflammatory cytokines BDNF, Htr1a, and IL-6 in the hippocampus. Nevertheless, no difference between stressed and control mice was observed neither in the sucrose preference nor in the open field test (except for vertical activity in OFT) at the age of 18 weeks. These findings reveal that 3-8 weeks of chronic stress could induce depression-like alterations in male C57BL/6J mice and the behavioral adaptation of aged mice might fail to the availability of the depression model.


Subject(s)
Aging/physiology , Behavior, Animal/physiology , Depression/physiopathology , Stress, Psychological/physiopathology , Animals , Depression/etiology , Disease Models, Animal , Male , Mice , Mice, Inbred C57BL , Stress, Psychological/complications
14.
Chinese Journal of School Health ; (12): 693-696, 2021.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-877131

ABSTRACT

Objective@#To understand mental health status of middle school students in Weifang, and to analyze its association with health risk behaviors, and to provide a reference basis for the effective prevention of mental health problems.@*Methods@#Using the self-designed questionnaire and Kessler l0 (K10), a total of 3 185 middle school students in Weifang selected by using stratified clustered sampling were investigated. Chi-square test and binary Logistic regression was used for statistical analysis.@*Results@#Among the middle school students in Weifang, 1 634(51.3%) reported good mental health, 854(26.8%) in moderate level, 394(12.4%) reported poor mental health, and 303(9.5%) reported very poor mental health. Sleep duration and smoking were associated with mental health of middle school students (P<0.05). Logistic regression analyses showed that, compared with adolescents with sleep duration less than 8 h, mental health among students whose sleep duration ≥8 h was better(OR=0.36); compared with non-smokers, students who smoked showed worse mental health status (OR=3.53).@*Conclusion@#Health-risk behaviors are closely related to mental health of middle school students. Relevant departments should strengthen education and publicity of healthy lifestyles, and pay close attention to the impact of health risk behaviors on mental health.

15.
Materials (Basel) ; 13(16)2020 Aug 05.
Article in English | MEDLINE | ID: mdl-32764251

ABSTRACT

During the bearing service, a series of microstructural evolutions will arise inside the material, such as the appearance of feature microstructures. The essential reason for the microstructural evolution is the cumulative effect of cyclic stress. The Hertz Contact formula is usually adopted to calculate the internal stress, and there is a correlation between the shape and distribution of the feature microstructure and the stress distribution. But it is insufficient to explain the relationship between the morphology of feature microstructures and the rolling direction, such as specific angles in butterfly and white etching bands. The rolling phenomenon will cause the asymmetry of stress distribution in the material, which is the source of the rolling friction coefficient. Moreover, slipping or microslip will produce additional stress components, which also cause the asymmetry of the stress field. However, there is no experimental or theoretical explanation for the relationship between the asymmetry of the stress field and the feature microstructure. According to the current theory, the appearance of feature microstructures is caused by stress with or without rolling. Therefore, it is of great significance to study the formation mechanism: whether feature microstructures will appear in the uniaxial cyclic compression stress field without rolling. In this paper, uniaxial cyclic compressive stress was loaded into a plate-ball system and a cylinder system. The characteristics of microstructural change of bearing steel (GCr15) were studied. It was found that the hardness of the material increased after the cyclic compressive load, and the inclusions interacted with the matrix material. In the local microregion a white etching area was found, although the scale is very small. No large-scale feature microstructures appeared. Other phenomena in the experiment are also described and analyzed. For example, the production of oil film in the contact area and the changing law of alternating load.

16.
Front Cell Dev Biol ; 8: 147, 2020.
Article in English | MEDLINE | ID: mdl-32266254

ABSTRACT

Acute kidney injury (AKI) is a serious clinical disease that is mainly caused by renal ischemia-reperfusion (I/R) injury, sepsis, and nephrotoxic drugs. The pathologic mechanism of AKI is very complex and may involve oxidative stress, inflammatory response, autophagy, apoptosis, and endoplasmic reticulum (ER) stress. The basic fibroblast growth factor (FGF2) is a canonic member of the FGF family that plays a crucial role in various cellular processes, including organ development, wound healing, and tissue regeneration. However, few studies have reported the potential therapeutic effect of FGF2 in the repair of renal ischemic injury in the past two decades. In the present study, we investigated the protective effect of FGF2 on renal I/R injury using Sprague-Dawley and NRK-52E cells. Our results showed that FGF2 significantly attenuates the apoptosis of kidney tissues after I/R injury through the inhibition of excessive ER stress. Moreover, FGF2 also alleviated the excessive ER stress and apoptosis in cultured NRK-52E cells injured by tert-Butyl hydroperoxide (TBHP). Significantly, phosphatidylinositol 3-kinase (PI3K)-selective inhibitor LY294002 and mitogen-activated protein kinase kinase (MEK)-selective inhibitor U0126 were utilized in the present study to examine the protective mechanism of FGF2. Our in vitro experimental results confirmed that both LY294002 and U0126 largely abolished the protective effect of FGF2. Taken together, the findings of the present study indicated that FGF2 attenuates I/R-induced renal epithelial apoptosis by suppressing excessive ER stress via the activation of the PI3K/AKT and MEK-ERK1/2 signaling pathways.

17.
Front Behav Neurosci ; 14: 622257, 2020.
Article in English | MEDLINE | ID: mdl-33613201

ABSTRACT

Background: Slit2 is a member of the Slit family of secreted glycoproteins that plays highly conserved roles in neuronal axon guidance and cellular migration. Our previous experimental results showed Alzheimer's disease-like alterations and increased permeability of the blood-brain barrier in Slit2-overexpressing transgenic (Slit2-Tg) mice aged 8-9 months. Nevertheless, relatively little is known about behavioral alterations in adult Slit2-Tg mice (2-6 months of age). To observe the age-related behavioral effects of Slit2 overexpression in adult mice, we performed a battery of behavioral tests with adult Slit2-Tg mice at 2-6 months of age. Results: The body weight of Slit2-Tg mice was lower than that of the wild-type mice from 15 weeks of age. Compared with the control mice, depression-like behaviors were found in Slit2-Tg mice from 15 to 21 weeks of age in the sucrose preference test, although Slit2-Tg mice were hyperactive in the tail suspension test. The anxiety-like behaviors were found in Slit2-Tg mice in the open field test, as well as increased locomotor activity. The anxiety-like behaviors were also found in adult Slit2-Tg mice in the elevated plus maze. Compared to wild-type mice at 23 weeks old, impairment of the hippocampal neurons were found in Slit2-Tg mice at the same age in hematoxylin-eosin staining (H&E), including some eccentric dispersion and expansion of neuronal bodies. In addition, the messenger RNA (mRNA) expression of TNF-α was elevated in the hippocampus of adult Slit2-Tg mice. Conclusions: Slit2 overexpression causes depression-/anxiety-like behaviors in adult mice that may be related to an increase in inflammatory factors and damage to hippocampal neurons.

18.
Surg Radiol Anat ; 41(9): 1019-1028, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31144009

ABSTRACT

PURPOSE: The aim of this study was to discuss the advantages of GQI reconstruction in the imaging of nerve fibers at crossing regions. Compared with DTI, the paper also discussed the advantages of GQI in imaging principles. METHODS: 3-T MRI data from five normal participants were reconstructed using GQI and DTI. After adjusting the parameters, we compared the differences in reconstructed nerve fibers at the crossing regions between the two methods. To complete this study, we chose four obvious examples (the optic nerve, the Superior cerebellar peduncles, the intersection of the pyramidal tract, the corpus callosum and the arcuate fibers and the intersection of the supplementary motor area (SMA) and the anterior part of arcuate fasciculus) to illustrate. RESULTS: By reconstructing nerve fibers in three regions, we can find that crossing-area images of nerve fibers significantly differed between DTI and GQI reconstruction. Although crossing fibers could be clearly and completely visualized after GQI reconstruction, they showed artifacts, incompleteness, deletions, and fractures after DTI reconstruction. After GQI reconstruction, we can find that there were two or more nerve fibers in each voxel. However, only one nerve fiber was present in each voxel after DTI reconstruction. CONCLUSION: The imaging of crossing fibers is more complete, consistent, and accurate when they are reconstructed by GQI than when they are reconstructed by DTI.


Subject(s)
Brain/diagnostic imaging , Diffusion Tensor Imaging , Image Processing, Computer-Assisted , Nerve Fibers , Adult , Artifacts , Brain/anatomy & histology , Female , Healthy Volunteers , Humans , Male , Middle Aged
19.
J Cell Mol Med ; 21(11): 2909-2925, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28544332

ABSTRACT

Ischaemia-reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI-induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model. FGF2 treatment greatly alleviated I/R-induced acute renal dysfunction and largely blunted I/R-induced elevation in serum creatinine and blood urea nitrogen, and also the number of TUNEL-positive tubular cells in the kidney. Mechanistically, FGF2 substantially ameliorated renal I/RI by mitigating several mitochondria damaging parameters including pro-apoptotic alteration of Bcl2/Bax expression, caspase-3 activation, loss of mitochondrial membrane potential and KATP channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the KATP channel blocker 5-HD. Interestingly, I/RI alone resulted in mild activation of FGFR, whereas FGF2 treatment led to more robust receptor activation. More significantly, post-I/RI administration of FGF2 also exhibited robust protection against I/RI by reducing cell apoptosis, inhibiting the release of damage-associated molecular pattern molecule HMBG1 and activation of its downstream inflammatory cytokines such as IL-1α, IL-6 and TNF α. Taken together, our data suggest that FGF2 offers effective protection against I/RI and improves animal survival by attenuating mitochondrial damage and HMGB1-mediated inflammatory response. Therefore, FGF2 has the potential to be used for the prevention and treatment of I/RI-induced AKI.


Subject(s)
Acute Kidney Injury/drug therapy , Fibroblast Growth Factor 2/pharmacology , Mitochondria/drug effects , Protective Agents/pharmacology , Reperfusion Injury/drug therapy , Acute Kidney Injury/genetics , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Animals , Apoptosis/drug effects , Apoptosis/genetics , Blood Urea Nitrogen , Caspase 3/genetics , Caspase 3/metabolism , Creatinine/blood , Gene Expression Regulation , Interleukins/genetics , Interleukins/metabolism , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Male , Membrane Potential, Mitochondrial/drug effects , Mitochondria/metabolism , Mitochondria/pathology , Potassium Channels/genetics , Potassium Channels/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Rats, Sprague-Dawley , Receptor, Fibroblast Growth Factor, Type 2/genetics , Receptor, Fibroblast Growth Factor, Type 2/metabolism , Reperfusion Injury/genetics , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Signal Transduction , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism
20.
Neurochem Res ; 41(4): 813-25, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26582233

ABSTRACT

Spinal cord injury (SCI) induces the disruption of the blood-spinal cord barrier (BSCB), which leads to infiltration of blood cells, inflammatory responses and neuronal cell death, with subsequent development of spinal cord secondary damage. Recent reports pointed to an important role of retinoic acid (RA), the active metabolite of the vitamin A, in the induction of the blood-brain barrier (BBB) during human and mouse development, however, it is unknown whether RA plays a role in maintaining BSCB integrity under the pathological conditions such as SCI. In this study, we investigated the BSCB protective role of RA both in vivo and in vitro and demonstrated that autophagy are involved in the BSCB protective effect of RA. Our data show that RA attenuated BSCB permeability and also attenuated the loss of tight junction molecules such as P120, ß-catenin, Occludin and Claudin5 after injury in vivo as well as in brain microvascular endothelial cells. In addition, RA administration improved functional recovery of the rat model of trauma. We also found that RA could significantly increase the expression of LC3-II and decrease the expression of p62 both in vivo and in vitro. Furthermore, combining RA with the autophagy inhibitor chloroquine (CQ) partially abolished its protective effect on the BSCB and exacerbated the loss of tight junctions. Together, our studies indicate that RA improved functional recovery in part by the prevention of BSCB disruption via the activation of autophagic flux after SCI.


Subject(s)
Autophagy , Spinal Cord Injuries/metabolism , Spinal Cord/blood supply , Tretinoin/pharmacology , Animals , Brain/blood supply , Catenins/metabolism , Cells, Cultured , Claudins/metabolism , Female , Humans , Microvessels/metabolism , Motor Activity/drug effects , Occludin/metabolism , Permeability , Rats, Sprague-Dawley , Spinal Cord/pathology , Spinal Cord/physiopathology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , beta Catenin/metabolism , Delta Catenin
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