Publications by authors named "Guo-Bao Wang"

27 Publications

  • Page 1 of 1

Simultaneous hyperaccumulation of rare earth elements, manganese and aluminum in Phytolacca americana in response to soil properties.

Chemosphere 2021 Nov 5;282:131096. Epub 2021 Jun 5.

School of Environmental Science and Engineering, Sun Yat-sen University, Guangzhou, 510006, China; Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology, Sun Yat-sen University, Guangzhou, 510006, China; Guangdong Provincial Engineering Research Center for Heavy Metal Contaminated Soil Remediation, Sun Yat-sen University, Guangzhou, 510006, China; Guangdong Laboratory for Lingnan Modern Agriculture, College of Natural Resources and Environment, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

The plant Phytolacca americana L. simultaneously hyperaccumulates manganese (Mn) and rare earth elements (REEs), but the underlying mechanisms are largely unknown. In this study, P. americana and the corresponding rhizosphere soil samples were collected from an ion-adsorption REE mine area in China, and the elemental composition and soil properties were analyzed in order to explore the relationship between metal accumulation and soil properties. The results show that P. americana accumulates high concentrations of REEs (up to 1040 mg kg), Mn (up to 10400 mg kg) and aluminum (Al) (up to 5960 mg kg) in leaves. The REE concentrations in leaves were positively correlated with those of Al, Fe and Zn, while light REE concentrations were negatively correlated with P concentrations (p < 0.05). The soil properties explained 81.7%, 72.9% and 67.1% of REEs, Mn and Al accumulated in P. americana, respectively. The variation of REE accumulation in P. americana was primarily explained by plant available P (24.4%), pH (12.9%), TOC (9.4%) and total P (7.7%). The accumulation of Mn was primarily explained by plant available REEs (42.9%) and available Al (13.1%) while Al in P. americana was primarily explained by soil pH (14.4%). This study suggests the potential by regulation of soil properties in improving the efficiency of phytoextraction for REEs by hyperaccumulators.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131096DOI Listing
November 2021

Effect of transjugular intrahepatic portosystemic shunt on transarterial chemoembolization for hepatocellular carcinoma: a systematic review and meta-analysis.

Diagn Interv Radiol 2021 Jul 28. Epub 2021 Jul 28.

Department of Minimally Invasive - Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China;Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University State Key Laboratory of Oncology in South China, Guangzhou, China.

Purpose: Hepatocellular carcinoma (HCC) usually occurs accompanied by portal hypertension. Transcatheter arterial chemoembolization (TACE) is recommended as an effective treatment in HCC. Recent studies had conflicting results regarding the effectiveness and safety of TACE for HCC in patients with transjugular intrahepatic portosystemic shunt (TIPS). This meta-analysis aimed to evaluate the influence of TIPS on the effectiveness and safety of TACE for patients with HCC.

Methods: A comprehensive search of studies among PubMed, Web of Science and Cochrane Library was conducted, from the earliest publishing date to January 27th, 2020. Statistical analyses were all performed using the Stata 13.0 software. I2 index statistic was used to assess heterogeneity.

Results: Six studies with a total of 536 patients with HCC were included in the analysis. The pooled response rate was 51% (95% CI: 25% to 77%) with a significant heterogeneity (I2=93.3%, p < 0.001). The TACE + TIPS group had an inferior response rate than the non-TIPS group, but the difference had no statistical significance (p = 0.171) and heterogeneity was low (I2=0.00%, p = 0.490). Pooled hepatic failure rate was 8.8% (95% CI: 5.2% to 12.4%) with low heterogeneity (I2=0.0%, p = 0.747). But the pooled hepatic failure rate increased to 12.7% (95% CI: 5.7% to 19.7%) with low heterogeneity (I2=11.5%, p = 0.323) if the patients who received TIPS after TACE were excluded.

Conclusion: TIPS does not influence the effectiveness of TACE, but attention should be paid to the risk of hepatic failure.
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http://dx.doi.org/10.5152/dir.2021.20358DOI Listing
July 2021

Simple Grading for Motor Function in Spastic Arm Paralysis: Hua-Shan Grading of Upper Extremity.

J Stroke Cerebrovasc Dis 2019 Aug 22;28(8):2140-2147. Epub 2019 May 22.

Department of Hand Surgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Department of Hand and Upper Extremity Surgery, Jing'an District Central Hospital, Shanghai, China; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China; State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center of Brain Science, Fudan University, Shanghai, China; Priority Among Priorities of Shanghai Municipal Clinical Medicine Center, Shanghai, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. Electronic address:

Objective: Spastic arm paralysis after central neurological injury has a long-term effect on the patient's quality of life. Effective neurosurgical treatment for this dysfunction has been described in our previous studies. It is of great significance to determine a set of unified and concise clinical standards for motor function grading in the neurosurgical treatment and management.

Methods: We first conducted a retrospective study that included 51 hemiplegic patients from the Neurosurgery and Microsurgery outpatient database of Huashan Hospital. The neurosurgeons cooperated with rehabilitation experts to design and administer the new rating system (Hua-Shan Grading of Upper Extremity, H-S grading) after analyzing the scale scores and video records of these patients. We then randomly enrolled 64 patients with unilateral spastic arm paralysis after stroke or brain trauma. The Fugl-Meyer Assessment, the Ashworth scale and the new grading system were applied and analyzed to evaluate the participants' motor function.

Results: Based on rehabilitation medicine scales and long-term follow-up, a feasible and concise grading system was applied that was based on the patients' characteristics and the examination experiences of neurosurgeons and rehabilitation experts in clinical practice. This method could effectively grade upper extremity motor function, usually in 3-5 minutes. A significant correlation was found between H-S grading and the Fugl-Meyer score by the Spearman test (r = .937, P < .01). The mean difference between any two levels of the new grading system was significant (P < .05). And good test-retest reliability, the Cronbach's alpha coefficient and the validity indices were presented. In addition, it was more sensitive to motor function compared with the Ashworth scale.

Conclusion: As a supplement to the classic scales, H-S grading was developed in the area of spastic hemiplegia treatment. It is standardized and simplified for patients in the chronic stage after central neurological injury.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.04.006DOI Listing
August 2019

Application of CUBE-STIR MRI and high-frequency ultrasound in contralateral cervical 7 nerve transfer surgery.

Br J Neurosurg 2019 Mar 12:1-6. Epub 2019 Mar 12.

a Department of Hand Surgery, Huashan Hospital, Shanghai Medical College , Fudan University , Shanghai , China.

Objective: The objective of the study was to investigate the feasibility of CUBE-SITR MRI and high-frequency ultrasound for the structural imaging of the brachial plexus to exclude neoplastic brachial plexopathy or structural variation and measure the lengths of anterior and posterior divisions of the C7 nerve, providing guidelines for surgeons before contralateral cervical 7 nerve transfer.

Methods: A total of 30 patients with CNS and 20 with brachial plexus injury were enrolled in this retrospective study. All patients underwent brachial plexus CUBE-STIR MRI and high-frequency ultrasound, and the lengths of the anterior and posterior divisions of C7 nerve were measured before surgery. Precise length of anterior and posterior divisions of contralateral C7 nerve was measured during surgery.

Results: MRI-measured lengths of anterior and posterior divisions of C7 nerves were positively correlated with that measured during surgery (anterior division, r = 0.94, p < .01; posterior division, r = 0.92, p < .01). High agreement was found between MRI-measured and intra-surgery measured length of anterior and posterior divisions of C7 nerve by BLAD-ALTMAN analysis. Ultrasonography could feasibly image supraclavicular C7 nerve and recognize small variant branches derived from middle trunk of C7 nerve root, which could be dissected intra-operatively and confirmed by electromyography during the procedure of contralateral C7 nerve transfer.

Conclusion: CUBE-STIR MRI had advantages for the imaging of the brachial plexus and measurement of the length of root-trunk-anterior/posterior divisions of C7 nerve. The clinical role of ultrasonography may be a simple way of evaluating general condition of C7 nerve and provide guidelines for contralateral C7 nerve transfer surgery.
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http://dx.doi.org/10.1080/02688697.2019.1584661DOI Listing
March 2019

Contralateral C7 to C7 nerve root transfer in reconstruction for treatment of total brachial plexus palsy: anatomical basis and preliminary clinical results.

J Neurosurg Spine 2018 Nov;29(5):491-499

1Department of Hand Surgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

OBJECTIVEContralateral C7 (CC7) nerve root has been used as a donor nerve for targeted neurotization in the treatment of total brachial plexus palsy (TBPP). The authors aimed to study the contribution of C7 to the innervation of specific upper-limb muscles and to explore the utility of C7 nerve root as a recipient nerve in the management of TBPP.METHODSThis was a 2-part investigation. 1) Anatomical study: the C7 nerve root was dissected and its individual branches were traced to the muscles in 5 embalmed adult cadavers bilaterally. 2) Clinical series: 6 patients with TBPP underwent CC7 nerve transfer to the middle trunk of the injured side. Outcomes were evaluated with the modified Medical Research Council scale and electromyography studies.RESULTSIn the anatomical study there were consistent and predominantly C7-derived nerve fibers in the lateral pectoral, thoracodorsal, and radial nerves. There was a minor contribution from C7 to the long thoracic nerve. The average distance from the C7 nerve root to the lateral pectoral nerve entry point of the pectoralis major was the shortest, at 10.3 ± 1.4 cm. In the clinical series the patients had been followed for a mean time of 30.8 ± 5.3 months postoperatively. At the latest follow-up, 5 of 6 patients regained M3 or higher power for shoulder adduction and elbow extension. Two patients regained M3 wrist extension. All regained some wrist and finger extension, but muscle strength was poor. Compound muscle action potentials were recorded from the pectoralis major at a mean follow-up of 6.7 ± 0.8 months; from the latissimus dorsi at 9.3 ± 1.4 months; from the triceps at 11.5 ± 1.4 months; from the wrist extensors at 17.2 ± 1.5 months; from the flexor carpi radialis at 17.0 ± 1.1 months; and from the digital extensors at 22.8 ± 2.0 months. The average sensory recovery of the index finger was S2. Transient paresthesia in the hand on the donor side, which resolved within 6 months postoperatively, was reported by all patients.CONCLUSIONSThe C7 nerve root contributes consistently to the lateral pectoral nerve, the thoracodorsal nerve, and long head of the triceps branch of the radial nerve. CC7 to C7 nerve transfer is a reconstructive option in the overall management plan for TBPP. It was safe and effective in restoring shoulder adduction and elbow extension in this patient series. However, recoveries of wrist and finger extensions are poor.
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http://dx.doi.org/10.3171/2018.3.SPINE171251DOI Listing
November 2018

Transcriptome Analysis of the Midgut of the Chinese Oak Silkworm Antheraea pernyi Infected with Antheraea pernyi Nucleopolyhedrovirus.

PLoS One 2016 7;11(11):e0165959. Epub 2016 Nov 7.

College of Plant Protection, Shenyang Agricultural University, Shenyang, 110866, China.

The Antheraea pernyi nucleopolyhedrovirus (ApNPV) is an exclusive pathogen of A. pernyi. The intense interactions between ApNPV and A. pernyi cause a series of physiological and pathological changes to A. pernyi. However, no detailed report exists regarding the molecular mechanisms underlying the interactions between ApNPV and A. pernyi. In this study, four cDNA libraries of the A. pernyi midgut, including two ApNPV-infected groups and two control groups, were constructed for transcriptomic analysis to provide new clues regarding the molecular mechanisms that underlie these interactions. The transcriptome of the A. pernyi midgut was de novo assembled using the Trinity platform because of the lack of a genome resource for A. pernyi. Compared with the controls, a total of 5,172 differentially expressed genes (DEGs) were identified, including 2,183 up-regulated and 2,989 down-regulated candidates, of which 2,965 and 911 DEGs were classified into different GO categories and KEGG pathways, respectively. The DEGs involved in A. pernyi innate immunity were classified into several categories, including heat-shock proteins, apoptosis-related proteins, serpins, serine proteases and cytochrome P450s. Our results suggested that these genes were related to the immune response of the A. pernyi midgut to ApNPV infection via their essential roles in regulating a variety of physiological processes. Our results may serve as a basis for future research not only on the molecular mechanisms of ApNPV invasion but also on the anti-ApNPV mechanism of A. pernyi.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165959PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098726PMC
June 2017

Evaluation of preoperative staging for esophageal squamous cell carcinoma.

World J Gastroenterol 2016 Aug;22(29):6683-9

Lin-Na Luo, Long-Jun He, Xiao-Yan Gao, Xin-Xin Huang, Hong-Bo Shan, Guang-Yu Luo, Yin Li, Shi-Yong Lin, Guo-Bao Wang, Rong Zhang, Guo-Liang Xu, Jian-Jun Li, Department of Endoscopy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Guangzhou 51006, Guangdong Province, China.

Esophageal squamous cell carcinoma (ESCC) is known for its rapid progression and poor outcomes. China has the highest incidence and mortality in the world. Diagnoses made at early stages and accurate staging are associated with better outcomes, all of which can play a significant role in the selection of treatment protocols. ESCC is staged according to the widely accepted TNM system. Common imaging modalities used in staging ESCC before treatment include endoscopy, computed tomography (CT), positron emission tomography (PET) and magnetic resonance imaging (MRI). Endoscopic ultrasound is useful for staging tumor depth and nodal status. Narrow band imaging is valuable for early stage disease assessment. CT and PET provide additional valuable information regarding node and metastasis staging. The ability of MRI to delineate ESCC is continuously being improved and adds information regarding locoregional status to routine examinations.
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http://dx.doi.org/10.3748/wjg.v22.i29.6683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970469PMC
August 2016

Endoscopic Ultrasound for Preoperative Esophageal Squamous Cell Carcinoma: a Meta-Analysis.

PLoS One 2016 7;11(7):e0158373. Epub 2016 Jul 7.

Department of Endoscopy, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: Treatment options and prognosis of esophageal squamous cell carcinoma (ESCC) depend on the primary tumor depth (T-staging) and regional lymph node status (N-staging). Endoscopic ultrasound (EUS) has emerged as a useful staging tool, but studies regarding its benefits have been variable. The objective of this study was to evaluate the diagnostic accuracy of EUS for detecting preoperative ESCC.

Methods: We included in our meta-analysis studies involving EUS-based staging of preoperative ESCC compared with pathological staging. Using a random-effects model, we performed a meta-analysis of the accuracy of EUS by calculating pooled estimates of sensitivity, specificity and the diagnostic odds ratio. In addition, we created a summary receiver operating characteristic (SROC) curve.

Results: Forty-four studies (n = 2880) met the inclusion criteria. The pooled sensitivity and specificity of T1 were 77% (95%CI: 73 to 80) and 95% (95%CI: 94 to 96). Among the T1 patients, EUS had a pooled sensitivity in differentiating T1a and T1b of 84% (95%CI: 80 to 88) and 83% (95%CI: 80 to 86), and a specificity of 91% (95%CI: 88 to 94) and 89% (95%CI: 86 to 92). To stage T4, EUS had a pooled sensitivity of 84% (95%CI: 79 to 89) and a specificity of 96% (95%CI: 95 to 97). The overall accuracy of EUS for T-staging was 79% (95%CI: 77 to 80), and for N-staging, 71% (95%CI: 69 to 73).

Conclusions: EUS has good diagnostic accuracy for staging ESCC, which has better performance in T1 sub-staging (T1a and T1b) and advanced disease (T4).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0158373PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936717PMC
July 2017

A preoperative mathematic model for computed tomographic guided microwave ablation treatment of hepatic dome tumors.

Oncotarget 2016 May;7(18):25949-59

Department of Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China.

Purpose: This study sought to prospectively evaluate the feasibility and safety of a preoperative mathematic model for computed tomographic(CT) guided microwave(MW) ablation treatment of hepatic dome tumors.

Methods: This mathematic model was a regular cylinder quantifying appropriate puncture routes from the bottom up. A total of 103 patients with hepatic dome tumors were enrolled and randomly divided into 2 groups based on whether this model was used or not: Group A (using the model; n = 43) versus Group B (not using the model; n = 60). All tumors were treated by CT-guided MW ablation and follow-up contrast CT were reviewed.

Results: The average number of times for successful puncture, average ablation time, and incidence of right shoulder pain were less in Group A than Group B (1.4 vs. 2.5, P = 0.001; 8.8 vs. 11.1 minutes, P = 0.003; and 4.7% vs. 20%, P = 0.039). The technical success rate was higher in Group A than Group B (97.7% vs. 85.0%, P = 0.032). There were no significant differences between the two groups in primary and secondary technique efficacy rates (97.7% vs. 88.3%, P = 0.081; 90.0% vs. 72.7%, P = 0.314). No major complications occurred in both groups.

Conclusion: The mathematic model of regular cylinder is feasible and safe for CT-guided MW ablation in treating hepatic dome tumors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041956PMC
http://dx.doi.org/10.18632/oncotarget.8299DOI Listing
May 2016

Shotgun proteomic analysis of Bombyx mori brain: emphasis on regulation of behavior and development of the nervous system.

Insect Sci 2016 Feb 5;23(1):15-27. Epub 2015 Mar 5.

College of Animal Science, Zhejiang University, Hangzhou, China.

The insect brain plays crucial roles in the regulation of growth and development and in all types of behavior. We used sodium dodecyl sulfate polyacrylamide gel electrophoresis and high-performance liquid chromatography - electron spray ionization tandem mass spectrometry (ESI-MS/MS) shotgun to identify the proteome of the silkworm brain, to investigate its protein composition and to understand their biological functions. A total of 2210 proteins with molecular weights in the range of 5.64-1539.82 kDa and isoelectric points in the range of 3.78-12.55 were identified. These proteins were annotated according to Gene Ontology Annotation into the categories of molecular function, biological process and cellular component. We characterized two categories of proteins: one includes behavior-related proteins involved in the regulation of behaviors, such as locomotion, reproduction and learning; the other consists of proteins related to the development or function of the nervous system. The identified proteins were classified into 283 different pathways according to KEGG analysis, including the PI3K-Akt signaling pathway which plays a crucial role in mediating survival signals in a wide range of neuronal cell types. This extensive protein profile provides a basis for further understanding of the physiological functions in the silkworm brain.
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http://dx.doi.org/10.1111/1744-7917.12195DOI Listing
February 2016

Endoscopic ultrasonography for staging of T1a and T1b esophageal squamous cell carcinoma.

World J Gastroenterol 2014 Feb;20(5):1340-7

Long-Jun He, Hong-Bo Shan, Guang-Yu Luo, Yin Li, Rong Zhang, Xiao-Yan Gao, Guo-Bao Wang, Shi-Yong Lin, Guo-Liang Xu, Jian-Jun Li, Department of Endoscopy, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou 510060, Guangdong Province, China.

Aim: To investigate the accuracy of Endoscopic ultrasound (EUS) in staging and sub-staging T1a and T1b esophageal squamous cell carcinoma (ESCC).

Methods: A retrospective analysis involving 72 patients with pathologically confirmed T1a or T1b ESCC, was undertaken between January 2005 and December 2011 in Sun Yat-sen University Cancer Center. The accuracy and efficiency of EUS for detecting stages T1a and T1b ESCC were examined.

Results: The overall accuracy of EUS for detecting stage T1a or T1b ESCC was 70.8% (51/72), and the sensitivity was 74.3%. 77.8% (7/9) of lesions originated in the upper thoracic region, 73.1% (38/52) in the mid-thoracic region and 72.7% (8/11) in the lower thoracic region. Multivariate analysis revealed that the diagnostic accuracy of EUS was closely related to lesion length (F = 4.984, P = 0.029).

Conclusion: EUS demonstrated median degree of accuracy for distinguishing between stages T1a and T1b ESCC. Therefore, it is necessary to improve EUS for staging early ESCC.
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http://dx.doi.org/10.3748/wjg.v20.i5.1340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921517PMC
February 2014

The role of insulin-like growth factor 1 and its receptor in the formation and development of colorectal carcinoma.

J Int Med Res 2013 Aug 25;41(4):1228-35. Epub 2013 Jun 25.

State Key Laboratory of Oncology in Southern China, Guangzhou, China.

Objective: To investigate the role of insulin-like growth factor (IGF)-1 and its receptor (IGF1R) in the formation and development of colorectal carcinoma.

Methods: Colorectal tissue and matching serum samples were collected from patients with adenomatous polyps or carcinoma and healthy control subjects. IGF1R mRNA levels were determined via quantitative real-time reverse transcription-polymerase chain reaction. Serum IGF1 was quantified using enzyme-linked immunosorbent assay.

Results: Serum IGF1 concentrations and mucosal IGF1R mRNA levels were significantly higher in patients with adenomatous polyps (n = 24) or carcinoma (n = 13) compared with healthy control subjects (n = 13). There was a significant positive correlation between serum IGF1 and mucosal IGF1R mRNA in patients with adenomatous polyps.

Conclusions: High circulating IGF1 concentrations and mucosal IGF1R expression may play important roles in both the formation and development of colorectal carcinoma. IGF1 and its receptor may be activated before carcinogenesis, and may promote the growth and malignant transformation of adenomatous polyps. IGF1 and IGF1R may be useful biomarkers for evaluating the stage and risk of carcinogenesis.
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http://dx.doi.org/10.1177/0300060513487631DOI Listing
August 2013

Changes in pathological pattern and treatment regimens based on repeat renal biopsy in lupus nephritis.

Chin Med J (Engl) 2012 Aug;125(16):2890-4

Division of Nephrology, Nanfang Hospital, Southern Medical University, Key Lab for Organ Failure Research, Ministry of Education, Guangzhou, Guangdong 510515, China.

Background: Relapses occur frequently in patients with lupus nephritis. Renal biopsy is the gold standard for assessing renal activity and hence guiding the treatment. Whether repeat renal biopsy is helpful during flares of lupus nephritis remains inconclusive. In the present study, we retrospectively reviewed the patients with lupus nephritis who had more than one renal biopsy with the hope to find the clinical value of repeat biopsy.

Methods: Patients who had a diagnosis of lupus nephritis and two or more renal biopsies were selected from the database of the patient pathology registration at this renal division. Renal biopsy was evaluated according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification of lupus nephritis. The pathological patterns and treatment regimens were analyzed after a repeat biopsy.

Results: We identified 44 systemic lupus erythematosus patients with serial renal biopsies. In total, there were 94 renal biopsies. Overall, the pathological transition occurred in 64% instances according to the ISN/RPS class. When the transition was analyzed according to proliferative, membranous or mix lesions, it showed different profile: 35% in patients with proliferative lesion, 23.5% patients with mix lesions, 100% in patients with pure membranous lesion. The pathological transition could not be predicted by any clinical characteristics. After the repeat renal biopsy, 34% of patients had a change in their treatment regimens.

Conclusions: The pathological conversion was very prevalent in patients with lupus nephritis. However, the transitions became less prevalent when they were analyzed according to pure membranous, proliferative, and mix lesion. Repeat biopsy might be helpful to avoid unnecessary increased immunosuppression therapy.
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August 2012

Advanced oxidation protein products activate intrarenal renin-angiotensin system via a CD36-mediated, redox-dependent pathway.

Antioxid Redox Signal 2013 Jan 30;18(1):19-35. Epub 2012 Jul 30.

Division of Nephrology, Nanfang Hospital, Southern Medical University, Key Lab for Organ Failure Research, Ministry of Education, Research Institute of Nephrology, Guangdong Province, Guangzhou, People's Republic of China.

Aims: Activation of intrarenal renin-angiotensin system (RAS) has a detrimental effect on the progression of chronic kidney diseases (CKDs), although the regulation of intrarenal RAS remains unclear. The aim of the present study was to evaluate the role of advanced oxidation protein products (AOPPs) in intrarenal RAS activation.

Results: AOPPs upregulated the expression of almost all components of RAS and increased activity of angiotensin-converting enzyme in cultured proximal tubular epithelial cells. The triggering effect of AOPP-albumin was 100-times stronger than that of unmodified albumin. The effect of AOPP-albumin was mainly mediated by a CD36-dependent, redox-sensitive signaling involving activation of protein kinase Cα, NADPH oxidase, and nuclear factor-κB/activation protein-1. Chronic AOPP-albumin loading in unilateral nephrectomy rats resulted in deposition of AOPPs in renal tubular cells accompanied with local RAS activation and functional perturbations such as increase in urinary albumin excretion. Accumulation of AOPPs was also detected in human renal tubular cells and correlated with expression of angiotensin II in renal biopsies from 19 patients with IgA nephropathy.

Innovation And Conclusion: This study demonstrated for the first time that AOPPs modified albumin functions as a strong trigger of intrarenal RAS via a CD36-mediated, redox-dependent pathway. Given the fact that accumulation of AOPPs is prevalent in diabetes and CKD, targeting AOPPs could be a strategy for the therapeutic intervention of CKD. Antioxid. Redox Signal. 18, 19-35.
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http://dx.doi.org/10.1089/ars.2012.4603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503474PMC
January 2013

Primary intestinal non-Hodgkin's lymphoma: a clinicopathologic analysis of 81 patients.

World J Gastroenterol 2011 Nov;17(41):4625-31

Department of Laser Treatment and Endoscopy, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China.

Aim: To analyze the clinicopathologic features and the prognosis of primary intestinal lymphoma.

Methods: Patients were included in the study based on standard diagnostic criteria for primary gastrointestinal lymphoma, and were treated at Sun Yat-sen University Cancer Centre between 1993 and 2008.

Results: The study comprised 81 adults. The most common site was the ileocaecal region. Twenty-two point two percent patients had low-grade B-cell lymphoma. Fifty-one point nine percent patients had high-grade B-cell lymphoma and 25.9% patients had T-cell lymphoma. Most patients had localized disease. There were more patients and more early stage diseases in the latter period, and the origin sites changed. The majority of patients received the combined treatment, and about 20% patients only received nonsurgical therapy. The wverall survival and event-free survival rates after 5 years were 71.6% and 60.9% respectively. The multivariate analysis revealed that small intestine and ileocaecal region localization, B-cell phenotype, and normal lactate dehydrogenase were independent prognostic factors for better patient survival. Surgery based treatment did not improve the survival rate.

Conclusion: Refined stratification of the patients according to the prognostic variables may allow individualized treatment. Conservative treatment may be an optimal therapeutic modality for selected patients.
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http://dx.doi.org/10.3748/wjg.v17.i41.4625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226984PMC
November 2011

[Clinical and pathological analysis of 25 cases of microscopic polyangiitis].

Nan Fang Yi Ke Da Xue Xue Bao 2011 Sep;31(9):1632-4

Department of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.E-mail:

Objective: To analyze the clinical and pathological features of microscopic polyangiitis (MPA) to improve the diagnosis and treatment of the disease.

Methods: Twenty-five cases of MPA were retrospectively analyzed.

Results: The onset symptoms of MPA, often nonspecific, included fever, muscle and joint pain, fatigue, loss of weight, etc, with varying degrees of proteinuria, hematuria and renal insufficiency. The pathological types revealed by renal biopsy were mainly focal segmental necrotizing glomerulonephritis or pauci-immune crescentic glomerulonephritis. Timely immunosuppressive therapy could improve the outcome.

Conclusion: The early symptoms of MPA are often nonspecific to easily result in misdiagnosis. Examination of ANCA titers and timely renal biopsy are helpful to establish an early diagnosis. Immune suppression therapy and plasma exchange when necessary should be initiated after the establishment of the diagnosis. The disease activity and drug toxicity should be carefully monitored to improve the prognosis.
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September 2011

Nephrotic syndrome after allogeneic hematopoietic stem cell transplantation: etiology and pathogenesis.

Blood Cells Mol Dis 2011 Feb 5;46(2):182-7. Epub 2011 Jan 5.

Hematology Department, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

In this study we investigated the etiology and pathogenesis of nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 257 patients with hematopoietic malignancies who survived more than 2 months post allo-HSCT. Associations of NS with the conditioning regimen, graft versus host disease (GVHD), and other variables were analyzed. Pathologic features of the kidney, regulatory T cells (Tregs), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were studied. NS was identified in 9 patients. The number of Tregs at day+30, 60, 90, and 180 was lower in NS patients than non-NS patients (P=0.001, 0.001, 0.007, 0.003). Serum levels of IFN-γ and TNF-α were higher in NS patients (P=0.032, 0.001, respectively). NS post allo-HSCT was associated with the occurrence of chronic GVHD (P=0.02). NS post-HSCT is an immune disorder that may involve immune complex deposition, Th1 cytokines, and Tregs.
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http://dx.doi.org/10.1016/j.bcmd.2010.12.003DOI Listing
February 2011

Arsenic Trioxide overcomes cell adhesion-mediated drug resistance through down-regulating the expression of beta(1)-integrin in K562 chronic myelogenous leukemia cell line.

Leuk Lymphoma 2010 Jun;51(6):1090-7

State Key Laboratory of Oncology in South China, Guangzhou, PR China.

The bone marrow microenvironment protects leukemia cells from drug-induced damage, and cell adhesion-mediated drug resistance (CAM-DR) is the main obstacle for the eradication of bone marrow minimal residual disease. In this study, we evaluated the survival response of K562 cells co-cultured with bone marrow stromal cells (BMSCs) derived from patients with chronic myelogenous leukemia (CML). Co-cultured K562 cells had a survival advantage after exposure to cytotoxic drugs compared to suspended K562 cells, but there was no survival difference between the two groups following exposure to As(2)O(3). The cytotoxicity of As(2)O(3) combined with cytotoxic drugs had an additive effect in the suspension group and a synergistic effect in the co-cultured group. Similar apoptotic responses were found using flow cytometry assays. As(2)O(3) treatment caused a dose dependent reduction of the adhesion ability of K562 cells to BMSCs, and Western blot analysis revealed that the treatment of K562 cells with As(2)O(3) led to down-regulation of beta(1)-integrin.
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http://dx.doi.org/10.3109/10428191003746315DOI Listing
June 2010

Accumulation of advanced oxidation protein products induces podocyte apoptosis and deletion through NADPH-dependent mechanisms.

Kidney Int 2009 Dec 2;76(11):1148-60. Epub 2009 Sep 2.

Division of Nephrology, Nanfang Hospital, Southern Medical University and Key Lab for Organ Failure Research, Ministry of Education, Guangzhou, P.R. China.

The accumulation of plasma advanced oxidation protein products (AOPPs) is prevalent in diverse disorders such as diabetes, metabolic syndromes, and chronic kidney disease. To study whether accumulated AOPPs have an important role in the progression of proteinuria and glomerulosclerosis, we chronically treated normal Sprague-Dawley rats with AOPP-modified rat serum albumin. Podocyte apoptosis was significantly increased coincident with the onset of albuminuria and preceded significant losses of glomerular podocytes. Increasing the amount of AOPPs in the media of conditionally immortalized podocytes rapidly triggered the production of intracellular superoxide by activation of NADPH oxidase and this, in turn, led to an upregulation of p53, Bax, caspase 3 activity, and apoptosis. Chronic inhibition of NADPH oxidase by apocynin prevented podocyte apoptosis, ameliorated podocyte depletion, and decreased albuminuria in AOPP-challenged rats. Our study demonstrates that accumulation of AOPPs promotes NADPH oxidase-dependent podocyte depletion by a p53-Bax apoptotic pathway both in vivo and in vitro.
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http://dx.doi.org/10.1038/ki.2009.322DOI Listing
December 2009

1,25-Dihydroxyvitamin D improved the free fatty-acid-induced insulin resistance in cultured C2C12 cells.

Diabetes Metab Res Rev 2008 Sep;24(6):459-64

Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

Background: Epidemiological evidence has indicated that vitamin D deficiency increased the risk of insulin resistance in metabolic syndrome. The present study was conducted to test the hypothesis that 1,25-dihydroxyvitamin D may improve the free fatty-acid (FFA)-induced insulin resistance in muscle cells.

Method: The insulin resistance of muscle cell model was established by treatment of FFA in differentiated C2C12 cells. Glucose uptake of C2C12 myotubes was analysed by the 3H-labelled 2-deoxyglucose uptake assay. The diameter of myotubes was measured under the condition of glutaraldehyde-induced autofluorescense. Tyrosine phosphorylated insulin receptor substrate 1 (IRS-1) was measured by immunoprecipitation. Serine phosphorylated IRS-1 and protein kinase B (Akt), extracellular signal-related kinase (ERK), c-Jun amino-terminal kinases (JNK) as well as their phosphorylated form were analysed by Western blots.

Results: Compared with a vehicle-treated group, FFA treatment in myotubes was associated with 70.6% reduction in insulin-mediated uptake of glucose, a five-fold increase in serine phosphorylation of IRS-1, 76.9% decrease in tyrosine phosphorylation of IRS-1 and 81.8% decrease in phosphorylation of Akt. Supplement of 1,25-dihydroxyvitamin D improved the FFA-induced inhibition of glucose uptake in a dose- dependent (p < 0.001) and time-dependent manner (p < 0.01). This was accompanied by increase in tyrosine phosphorylation of IRS-1 and phosphorylated Akt and decrease in serine phosphorylation of IRS-1 (p < 0.001). 1,25-Dihydroxyvitamin D also inhibited the FFA-induced reduction in myotube diameter by 35.3% (p < 0.001). JNK phosphorylation was reduced by 126.7% with treatment of 1,25-dihydroxyvitamin D (p < 0.001). 1,25-Dihydroxyvitamin D had no effect on FFA-induced ERK phosphorylation (p = 0.84).

Conclusion: 1,25-Dihydroxyvitamin D improved the FFA-induced insulin resistance in muscle cells.
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http://dx.doi.org/10.1002/dmrr.873DOI Listing
September 2008

Advanced oxidation protein products promote inflammation in diabetic kidney through activation of renal nicotinamide adenine dinucleotide phosphate oxidase.

Endocrinology 2008 Apr 3;149(4):1829-39. Epub 2008 Jan 3.

Division of Nephrology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, People's Republic of China.

The involvement of inflammatory processes has been recognized in development and/or progression of diabetic nephropathy. However, the mechanisms involved in the pathogenesis of renal inflammation have not been completely understood. In this study, we tested the hypothesis that accumulation of advanced oxidation protein products (AOPPs), which occurs in diabetes, may promote inflammatory responses in diabetic kidney. Streptozotocin-induced diabetic rats were randomized to iv injection of vehicle, native rat serum albumin (RSA), and AOPPs-modified RSA (AOPPs-RSA) in the presence or absence of oral administration of apocynin. A control group was followed concurrently. Compared with RSA- or vehicle-treated diabetic rats, AOPPs-RSA-treated animals displayed significant increase in renal macrophage infiltration and overexpression of monocyte chemoattractant protein-1 and TGF-beta1. This was associated with deteriorated structural and functional abnormalities of diabetic kidney, such as glomerular hypertrophy, fibronectin accumulation, and albuminuria. AOPP challenge significantly increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent superoxide generation in renal homogenates and up-regulated membrane expression of renal NADPH oxidase subunits p47(phox) and gp91(phox). All these AOPPs-induced perturbations in diabetic kidney could be prevented by the NADPH oxidase inhibitor apocynin. These data suggest that chronic accumulation of AOPPs may promote renal inflammation in diabetes probably through activation of renal NADPH oxidase.
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http://dx.doi.org/10.1210/en.2007-1544DOI Listing
April 2008

Advanced oxidation protein products accelerate renal fibrosis in a remnant kidney model.

J Am Soc Nephrol 2007 Feb 3;18(2):528-38. Epub 2007 Jan 3.

Division of Nephrology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, People's Republic of China.

Accumulation of plasma advanced oxidation protein products (AOPP) has been found in patients with chronic kidney disease. However, the biologic consequences of AOPP consumption on progression of renal disease still are unclear. For testing of the hypothesis that AOPP accelerate progression of chronic kidney disease, Sprague-Dawley rats were subjected to five-sixths nephrectomy (5/6 Nx) or to sham operation. Rats in each group were randomly assigned in three subgroups (n = 30 in each group) and treated with repeated intravenous injections of AOPP-modified rat serum albumin (RSA), unmodified RSA, or vehicle for indicated period. Compared with RSA- or vehicle-treated 5/6 Nx rats, AOPP RSA-treated 5/6 Nx rats displayed greater proteinuria, higher serum creatinine, and lower creatinine clearance. AOPP challenge resulted in more renal hypertrophy, higher macrophage influx, and greater renal fibrosis in the remnant kidney. Chronic administration of AOPP in sham-operated rats increased urinary protein excretion and renal macrophage infiltration, but histologic renal fibrosis was not observed during the study period. AOPP treatment enhanced AOPP level in renal tissue. This was associated with marked increase of thiobarbituric acid reactive substances, decrease of glutathione peroxidase activity, and upregulated expression of monocyte chemoattractant protein-1 and TGF-beta1 in renal cortex. These data indicate that AOPP might be a new and potentially important mediator of renal fibrosis in the remnant kidney. Chronic accumulation of AOPP promotes renal fibrosis probably via a redox-sensitive inflammatory pathway.
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http://dx.doi.org/10.1681/ASN.2006070781DOI Listing
February 2007

Advanced oxidation protein products accelerate atherosclerosis through promoting oxidative stress and inflammation.

Arterioscler Thromb Vasc Biol 2006 May 23;26(5):1156-62. Epub 2006 Feb 23.

Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.

Objective: Increased level of plasma advanced oxidation protein products (AOPPs) has been found in patients with uremia and nonuremic subjects with coronary artery disease. This study was conducted to test the hypothesis that AOPPs play a causal role in atherosclerosis.

Methods And Results: Hypercholesterolemic (0.5% wt/wt diet) or normal rabbits received either repeated intravenous injections of AOPPs modified rabbit serum albumin (AOPPs-RSA) or unmodified RSA for 8 weeks. Compared with RSA- or vehicle-treated hypercholesterolemic rabbits, AOPPs-RSA-treated animals displayed increased atherosclerotic plaque area oxidized low-density lipoprotein (oxLDL) deposition, macrophage infiltration, and smooth muscle cell proliferation. Aortic sections from AOPPs-RSA-treated normal rabbits showed significant focal intima proliferation and mild Oil-Red-O staining lipid deposition in the affected areas, a phenomenon not observed in the RSA- or vehicle-treated controls. Plasma AOPPs levels in AOPPs-treated groups significantly increased in both hypercholesterolemic and normal rabbits compared with their relevant controls. Close correlations were found between plasma levels of AOPPs and the parameters of oxidative stress, eg, oxLDL and thiobarbituric acid reactive substances levels, or glutathione peroxidase activity. A highly significant correlation was also observed between plasma AOPPs and tumor necrosis factor (TNF)-alpha levels.

Conclusions: This study provides in vivo evidence for a causal relationship between chronic AOPPs accumulation and atherosclerosis.
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http://dx.doi.org/10.1161/01.ATV.0000214960.85469.68DOI Listing
May 2006

Efficacy and safety of benazepril for advanced chronic renal insufficiency.

N Engl J Med 2006 Jan;354(2):131-40

Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: Angiotensin-converting-enzyme inhibitors provide renal protection in patients with mild-to-moderate renal insufficiency (serum creatinine level, 3.0 mg per deciliter or less). We assessed the efficacy and safety of benazepril in patients without diabetes who had advanced renal insufficiency.

Methods: We enrolled 422 patients in a randomized, double-blind study. After an eight-week run-in period, 104 patients with serum creatinine levels of 1.5 to 3.0 mg per deciliter (group 1) received 20 mg of benazepril per day, whereas 224 patients with serum creatinine levels of 3.1 to 5.0 mg per deciliter (group 2) were randomly assigned to receive 20 mg of benazepril per day (112 patients) or placebo (112 patients) and then followed for a mean of 3.4 years. All patients received conventional antihypertensive therapy. The primary outcome was the composite of a doubling of the serum creatinine level, end-stage renal disease, or death. Secondary end points included changes in the level of proteinuria and the rate of progression of renal disease.

Results: Of 102 patients in group 1, 22 (22 percent) reached the primary end point, as compared with 44 of 108 patients given benazepril in group 2 (41 percent) and 65 of 107 patients given placebo in group 2 (60 percent). As compared with placebo, benazepril was associated with a 43 percent reduction in the risk of the primary end point in group 2 (P=0.005). This benefit did not appear to be attributable to blood-pressure control. Benazepril therapy was associated with a 52 percent reduction in the level of proteinuria and a reduction of 23 percent in the rate of decline in renal function. The overall incidence of major adverse events in the benazepril and placebo subgroups of group 2 was similar.

Conclusions: Benazepril conferred substantial renal benefits in patients without diabetes who had advanced renal insufficiency. (ClinicalTrials.gov number, NCT00270426.)
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http://dx.doi.org/10.1056/NEJMoa053107DOI Listing
January 2006

[Treatment of proliferative lupus nephritis with leflunomide and steroid: a prospective multi-center controlled clinical trial].

Zhonghua Nei Ke Za Zhi 2005 Sep;44(9):672-6

Renal Division and Institute of Nephrology, First Hospital, Peking University, Beijing 100034, China.

Objective: Leflunomide (LEF) is a selective inhibitor of de novo pyrimidine synthesis, currently used in the treatment of rheumatoid arthritis. To evaluate the efficacy and safety of LEF in the treatment of proliferative lupus nephritis, a prospective multi-center controlled clinical trial was conducted.

Methods: Patients with biopsy-confirmed proliferative lupus nephritis were recruited. Patients of recent onset who had not used any immunosuppressive drug were given either oral LEF (group A) or IV cyclophosphamide (group B); relapsed patients who had received immunosuppressive therapy 3 months before were given LEF (group C). Efficacy and safety were evaluated at 6 months after treatment.

Results: Total 51 patients were enrolled, 4 patients withdrew due to adverse events. For those initial treated patients, total response rate were 80% in group A and 75% in group B, complete remission rate were 40% and 25% respectively, not statistically different. Renal parameters (proteinuria, serum albumin and serum creatinine) and systemic lupus erythematosus disease activity index (SLEDAI) improved similarly in both groups. For 14 relapsed patients, total response rate was 60% and complete remission rate was 6.7%. Major adverse events reported in LEF treated patients were infection and alopecia. Herpes zoster was the most often type among infectious events, and one case of severe lung infection was reported.

Conclusion: LEF combined with steroid was effective in the induction therapy of proliferative lupus nephritis. LEF was generally well-tolerated, its efficacy in maintenance therapy and long-term safety remains to be clarified.
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September 2005

[Advanced glycation end products accelerate atherosclerosis via enhancement of oxidative stress].

Zhonghua Yi Xue Za Zhi 2004 Jul;84(13):1066-72

Department of Nephrology, Nanfang Hospital, Guangzhou 510515, China.

Objective: To investigate the effect of advanced glycation end products (AGE) on atheromatous plaque formation and its possible mechanisms.

Methods: Fifty rabbits were randomly divided into five groups of 10 rabbits: group A, fed with hypercholesterolemic diet and injected intravenously with AGE modified rabbit serum albumin (AGE-RSA); group B, fed with hypercholesterolemic diet and injected with unmodified RSA; group C, fed with hypercholesterolemic diet; group D, fed with normal diet alone: and group E, fed with normal diet and injected with AGE-RSA. Ten weeks after the rabbits were killed. Their aortas were taken out and stained with Sudan red IV. The extent of atheromatous plaques in the aortas en face was evaluated by computer-assisted morphometry and by histologic examination. Photoshop system was used to measure the percentage of atheromatous plaques in the area of tunica intima. The depositions of AGE, malondialdehyde modified low-density lipoprotein (MDA-LDL), oxidized low-density lipoprotein (ox-LDL) and expression of receptor of AGE (RAGE) in aortic tissue were detected by using immunohistological staining. The circulating AGE, blood lipids, serum selenium glutathione peroxydase (SeGSHPx) activity, malonyldialdehyde (MDA), and oxidized LDL (ox-LDL) were detected before the experiment and after the rabbits were killed.

Results: (1) The relative plaque area was significantly increased in group A (50% +/- 8%) compared with in group B (21% +/- 7%) and group C (29% +/- 6%). No plaque could be found in animals fed with normal diet (group D) even in those receiving repeated injections of AGE-RSA (group E). Depositions of ox-LDL, MDA-LDL and AGE in atherosclerotic lesions increased and RAGE expression were upregulated in the rabbits fed with hypercholesterolemic diet and injected with AGE-RSA (group A) compared with the other four groups. (2) All hypercholesterolemic rabbits showed comparable serum levels of triglyceride and cholesterol. However, the serum levels of AGE, ox-LDL and MDA were significantly higher and the serum level of SeGSHPx was relatively lower in group A compared with those in the other four groups. (3) The serum level of AGE was directly correlated with the serum ox-LDL (r = 0.459, P < 0.01) or serum MDA concentration (r = 0.423, P < 0.05), and inversely correlated with the serum level of SeGSHPx (r = - 0.448, P < 0.01). A close correlation was found between the serum level of AGE and endothelium RAGE expression (r = 0.384, P < 0.05) and deposition area of AGE (r = 0.468, P < 0.05) in aorta.

Conclusion: AGE accelerates the atheromatous plaque formation through induction of oxidative stress and upregulation of RAGE.
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July 2004

Receptor for advanced glycation end products on human synovial fibroblasts: role in the pathogenesis of dialysis-related amyloidosis.

J Am Soc Nephrol 2002 May;13(5):1296-1306

*Division of Nephrology, Nanfang Hospital, Guangzhou, People's Republic of China; Department of Surgery, Columbia University, College of Physicians and Surgeons, New York, New York; and Institute of Renal Outcomes Research and Health Policy, Duke University Medical Center, Durham, North Carolina.

An important component of amyloid fibrils in dialysis-related amyloidosis (DRA) is beta(2)-microglobulin (beta(2)m) modified with advanced glycation end products (AGE). The amyloid deposits are located principally in joint structures, with adjacent chronic inflammatory reaction characterized by monocyte infiltration. This study examined the interaction of AGE-beta(2)m with human synovial fibroblasts and investigated the proinflammatory effects of that interaction. It was demonstrated that human synovial fibroblasts constitutively expressed the receptor for AGE (RAGE). RAGE expression was detected mainly in synovial intima and was upregulated in DRA synovium. (125)I-AGE-beta(2)m bound to immobilized human synovial fibroblasts in a specific, dose-dependent manner (K(d) of approximately 138.0 nM), and binding was inhibited by anti-RAGE IgG. Incubation of human synovial fibroblasts with AGE-beta(2)m induced degradation of this AGE-modified protein, as well as increased monocyte chemoattractant protein-1 (MCP-1) mRNA and protein expression. The amount of MCP-1 produced by AGE-beta(2)m-stimulated human synovial fibroblasts was sufficient to induce the chemotaxis of monocytes. MCP-1 synthesis resulted from engagement of RAGE, because the increase in MCP-1 synthesis was attenuated by preincubation of human synovial fibroblasts with anti-RAGE IgG. These data provide evidence of RAGE-mediated perturbation of human synoviocytes, which may be involved in the pathogenesis of inflammatory processes associated with DRA.
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http://dx.doi.org/10.1681/ASN.V1351296DOI Listing
May 2002
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