1.Effects of Polygonum cuspidatum on AMPK-FOXO3α Signaling Pathway in Rat Model of Uric Acid-Induced Renal Damage.
Wei-Guo MA ; Jie WANG ; Xiang-Wei BU ; Hong-Hong ZHANG ; Jian-Ping ZHANG ; Xiao-Xu ZHANG ; Yu-Xi HE ; Da-Li WANG ; Zheng-Ju ZHANG ; Feng-Xian MENG
Chinese journal of integrative medicine 2019;25(3):182-189
BACKGROUND:
To observe the effects of Chinese medicine (CM) Polygonum cuspidatum (PC) on adenosine 5'-monophosphate-activated protein kinase (AMPK), forkhead box O3α (FOXO3α), Toll-like receptor-4 (TLR4), NACHT, LRR and PYD domains-containing protein 3 (NLRP3), and monocyte chemoattractant protein-1 (MCP-1) expression in a rat model of uric acid-induced renal damage and to determine the molecular mechanism.
METHODS:
A rat model of uric acid-induced renal damage was established, and rats were randomly divided into a model group, a positive drug group, and high-, medium-, and low-dose PC groups (n=12 per group). A normal group (n=6) was used as the control. Rats in the normal and model groups were administered distilled water (10 mL•kg) by intragastric infusion. Rats in the positive drug group and the high-, medium-, and low-dose PC groups were administered allopurinol (23.33 mg•kg), and 7.46, 3.73, or 1.87 g•kg•d PC by intragastric infusion, respectively for 6 to 8 weeks. After the intervention, reverse transcription polymerase chain reaction, Western blot, enzyme linked immunosorbent assay, and immunohistochemistry were used to detect AMPK, FOXO3α, TLR4, NLRP3, and MCP-1 mRNA and protein levels in renal tissue or serum.
RESULTS:
Compared with the normal group, the mRNA transcription levels of AMPK and FOXO3α in the model group were significantly down-regulated, and protein levels of AMPKα1, pAMPKα1 and FOXO3α were significantly down-regulated at the 6th and 8th weeks (P<0.01 or P<0.05). The mRNA transcription and protein levels of TLR4, NLRP3 and MCP-1 were significantly up-regulated (P<0.01 or P<0.05). Compared with the model group, at the 6th week, the mRNA transcription levels of AMPK in the high- and medium-dose groups, and protein expression levels of AMPKα1, pAMPKα1 and FOXO3α in the high-dose PC group, AMPKα1 and pAMPKα1 in the mediumdose PC group, and pAMPKα1 in the low-dose PC group were significantly up-regulated (P<0.01 or P<0.05); the mRNA transcription and protein levels of TLR4 and NLRP3 in the 3 CM groups, and protein expression levels of MCP-1 in the medium- and low-dose PC groups were down-regulated (P<0.01 or P<0.05). At the 8th week, the mRNA transcription levels of AMPK in the high-dose PC group and FOXO3α in the medium-dose PC group, and protein levels of AMPKα1, pAMPKα1 and FOXO3α in the 3 CM groups were significantly up-regulated (P<0.01 or P<0.05); the mRNA transcription levels of TLR4 in the medium- and low-dose PC groups, NLRP3 in the high- and low-dose PC groups and MCP-1 in the medium- and low-dose PC groups, and protein expression levels of TLR4, NLRP3 and MCP-1 in the 3 CM groups were down-regulated (P<0.01 or P<0.05).
CONCLUSION
PC up-regulated the expression of AMPK and its downstream molecule FOXO3α and inhibited the biological activity of TLR4, NLRP3, and MCP-1, key signal molecules in the immunoinflammatory network pathway, which may be the molecular mechanism of PC to improve hyperuricemia-mediated immunoinflflammatory metabolic renal damage.
AMP-Activated Protein Kinases
;
physiology
;
Animals
;
Chemokine CCL2
;
blood
;
Disease Models, Animal
;
Fallopia japonica
;
Forkhead Box Protein O3
;
physiology
;
Hyperuricemia
;
complications
;
Kidney Diseases
;
drug therapy
;
etiology
;
Male
;
Plant Extracts
;
pharmacology
;
Rats
;
Rats, Sprague-Dawley
;
Signal Transduction
;
drug effects
;
Uric Acid
2.Association of hypoalbuminemia with acute kidney injury in children after cardiac surgery.
Lian DUAN ; Guo-Huang HU ; Meng JIANG ; Cheng-Liang ZHANG ; Yan-Ying DUAN
Chinese Journal of Contemporary Pediatrics 2018;20(6):475-480
OBJECTIVETo study whether hypoalbuminemia after pediatric cardiopulmonary bypass (CPB) for cardiac surgery is a risk factor for postoperative acute kidney injury (AKI).
METHODSA retrospective analysis was performed on the clinical data of 1 110 children who underwent CPB surgery between 2012 and 2016. According to the minimum serum albumin within 48 hours postoperatively, these patients were divided into hypoalbuminemia group (≤35 g/L) and normal albumin group (>35 g/L). The two groups were compared in terms of perioperative data and the incidence of AKI. Furthermore, the incidence of AKI was compared again after propensity score matching for the unbalanced factors during the perioperative period. The perioperative risk factors for postoperative AKI were analyzed by logistic regression.
RESULTSThe overall incidence rate of postoperative AKI was 13.78% (153/1 110), and the mortality rate was 2.52% (28/1 110). The mortality rate of children with AKI was 13.1% (20/153). The patients with hypoalbuminemia after surgery (≤35 g/L) accounted for 44.50% (494/1 110). Before and after propensity score matching, the hypoalbuminemia group had a significantly higher incidence of AKI than the normal albumin group (P<0.05). The children with AKI had a significantly lower serum albumin level after surgery than those without AKI (P<0.05). The multivariate logistic regression analysis showed albumin ≤35 g/L was one of the independent risk factors for postoperative AKI.
CONCLUSIONSAlbumin ≤35 g/L within 48 hours postoperatively is an independent risk factor for postoperative AKI in children after CPB surgery.
Acute Kidney Injury ; epidemiology ; etiology ; Adolescent ; Cardiopulmonary Bypass ; adverse effects ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Heart Diseases ; surgery ; Humans ; Hypoalbuminemia ; epidemiology ; etiology ; Infant ; Infant, Newborn ; Male ; Perioperative Period ; Postoperative Complications ; epidemiology ; etiology ; Propensity Score ; Retrospective Studies
3.Relationships of Inflammatory Factors and Risk Factors with Different Target Organ Damage in Essential Hypertension Patients.
Chun-Lin LAI ; Jin-Ping XING ; Xiao-Hong LIU ; Jie QI ; Jian-Qiang ZHAO ; You-Rui JI ; Wu-Xiao YANG ; Pu-Juan YAN ; Chun-Yan LUO ; Lu-Fang RUAN
Chinese Medical Journal 2017;130(11):1296-1302
BACKGROUNDAtherosclerosis (AS) is an inflammatory disease. Inflammation was considered to play a role in the whole process of AS. This study aimed to analyze the relationships of inflammatory factors and risk factors with different target organ damages (TOD) in essential hypertension (EH) patients and to explore its clinical significance.
METHODSA total of 294 EH patients were selected and divided into four groups according to their conditions of TOD. Forty-eight healthy subjects were selected as control. The clinical biochemical parameters, serum amyloid A, serum tryptase, and lipoprotein-associated phospholipase A2 (Lp-PLA2) in each group were detected, and the related risk factors were also statistically analyzed.
RESULTSFibrinogen (Fbg) was the most significant independent risk factor in acute coronary syndrome (ACS) group (odds ratio [OR]: 22.242, 95% confidence interval [CI]: 6.458-76.609, P< 0.001) with the largest absolute value of the standardized partial regression coefficient B' (b': 1.079). Lp-PLA2 was the most significant independent risk factor in stroke group (OR: 13.699, 95% CI: 5.236-35.837, P< 0.001) with b' = 0.708. Uric acid (UA) was the most significant independent risk factor in renal damage group (OR: 15.307, 95% CI: 4.022-58.250, P< 0.001) with b' = 1.026.
CONCLUSIONSFbg, Lp-PLA2, and UA are the strongest independent risk factors toward the occurrence of ACS, ischemic stroke, and renal damage in EH patients, thus exhibiting the greatest impacts on the occurrence of ACS, ischemic stroke, and renal damage in EH patients, respectively.
1-Alkyl-2-acetylglycerophosphocholine Esterase ; Aged ; Antihypertensive Agents ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Essential Hypertension ; blood ; complications ; drug therapy ; physiopathology ; Female ; Humans ; Kidney Diseases ; blood ; etiology ; physiopathology ; Logistic Models ; Male ; Middle Aged ; Renal Insufficiency, Chronic ; blood ; etiology ; physiopathology ; Risk Factors ; Serum Amyloid A Protein ; metabolism ; Stroke ; blood ; etiology ; physiopathology ; Tryptases ; blood
4.Umbilicus application of Huobi Powder for ED with kidney deficiency dampness: A randomized controlled clinical trial.
Run-Biao DONG ; Guang-Sen LI ; De-Gui CHANG ; Jian CAI ; Qu AN
National Journal of Andrology 2017;23(11):1014-1019
Objective:
To prove the clinical efficacy of umbilicus application of Huobi Powder for the treatment of erectile dysfunction (ED) with the traditional Chinese medicine (TCM) syndrome of kidney deficiency dampness by related clinical indexes.
METHODS:
This randomized controlled double-blind clinical study included 72 ED patients with the TCM syndrome of kidney deficiency dampness treated by 12-hour application of Huobi Powder (the trial group, n = 36) or placebo (the control group, n = 36) to the umbilicus qd for 28 consecutive days. We recorded the IIEF-5 and Erection Quality Scale (EQS) scores, TCM syndrome indexes, radial rigidity of the erectile penis, and the angle of penile erection before and after treatment. We established a database with the collected data and performed statistical analysis with the SPSS21.0 software.
RESULTS:
Statistically significant differences were observed after treatment between the trial and control groups in the TCM syndrome-based efficacy (69.44% vs 36.11%, P <0.01) and Western medicine-based clinical effectiveness (77.78% vs 36.11%, P <0.01). The trial group, as compared with the control, showed remarkably decreased TCM syndrome indexes (18.19 ± 9.12 vs 12.97 ± 11.92, P <0.05), increased IIEF-5 score (13.83 ± 4.91 vs 18.67 ± 3.09, P <0.01), radial rigidity of the erectile penis ([53.43 ± 11.05]% vs [71.96 ± 12.92]%, P <0.01) and the angle of penile erection ([42.15 ± 11.77]% vs [66.96 ± 12.34]%, P <0.01), but no significant difference in the EQS score (37.11 ± 16.70 vs 35.33 ± 14.11, P >0.05).
CONCLUSIONS
Umbilicus application of Huobi Powder has a definite clinical effect on ED with the TCM syndrome of kidney deficiency dampness.
Double-Blind Method
;
Drugs, Chinese Herbal
;
administration & dosage
;
Erectile Dysfunction
;
drug therapy
;
etiology
;
Humans
;
Kidney Diseases
;
complications
;
drug therapy
;
Male
;
Medicine, Chinese Traditional
;
Penile Erection
;
Powders
;
administration & dosage
;
Treatment Outcome
;
Umbilicus
5.AST-120 Improves Microvascular Endothelial Dysfunction in End-Stage Renal Disease Patients Receiving Hemodialysis.
Jung Hwa RYU ; Mina YU ; Sihna LEE ; Dong Ryeol RYU ; Seung Jung KIM ; Duk Hee KANG ; Kyu Bok CHOI
Yonsei Medical Journal 2016;57(4):942-949
PURPOSE: Endothelial dysfunction (ED) is a pivotal phenomenon in the development of cardiovascular disease (CVD) in patients receiving hemodialysis (HD). Indoxyl sulfate (IS) is a known uremic toxin that induces ED in patients with chronic kidney disease. The aim of this study was to investigate whether AST-120, an absorbent of IS, improves microvascular or macrovascular ED in HD patients. MATERIALS AND METHODS: We conducted a prospective, case-controlled trial. Fourteen patients each were enrolled in respective AST-120 and control groups. The subjects in the AST-120 group were treated with AST-120 (6 g/day) for 6 months. Microvascular function was assessed by laser Doppler flowmetry using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) at baseline and again at 3 and 6 months. Carotid arterial intima-media thickness (cIMT) and flow-mediated vasodilation were measured at baseline and 6 months. The Wilcoxon rank test was used to compare values before and after AST-120 treatment. RESULTS: Ach-induced iontophoresis (endothelium-dependent response) was dramatically ameliorated at 3 months and 6 months in the AST-120 group. SNP-induced response showed delayed improvement only at 6 months in the AST-120 group. The IS level was decreased at 3 months in the AST-120 group, but remained stable thereafter. cIMT was significantly reduced after AST-120 treatment. No significant complications in patients taking AST-120 were reported. CONCLUSION: AST-120 ameliorated microvascular ED and cIMT in HD patients. A randomized study including a larger population will be required to establish a definitive role of AST-120 as a preventive medication for CVD in HD patients.
Acetylcholine
;
Adult
;
Carbon/*therapeutic use
;
Cardiovascular Diseases/etiology/*prevention & control
;
Carotid Intima-Media Thickness
;
Endothelium, Vascular/*physiopathology
;
Female
;
Humans
;
Iontophoresis
;
Kidney Failure, Chronic/complications/*physiopathology/*therapy
;
Laser-Doppler Flowmetry
;
Male
;
Microcirculation/physiology
;
Middle Aged
;
Nitroprusside
;
Oxides/*therapeutic use
;
Prospective Studies
;
*Renal Dialysis
;
Young Adult
6.Renal Parenchymal Malakoplakia Presenting as Acute Renal Failure in a Young Woman.
Guo-Qin WANG ; Xiao-Yi XU ; Yi-Pu CHEN ; Hong CHENG
Chinese Medical Journal 2016;129(15):1880-1881
Acute Kidney Injury
;
diagnosis
;
drug therapy
;
etiology
;
Adult
;
Anti-Bacterial Agents
;
therapeutic use
;
Cyclophosphamide
;
therapeutic use
;
Female
;
Humans
;
Kidney Diseases
;
diagnosis
;
drug therapy
;
Levofloxacin
;
therapeutic use
;
Malacoplakia
;
complications
;
diagnosis
;
drug therapy
;
Prednisone
;
therapeutic use
7.Predictive Factors of Mortality in Population of Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH): Results from a Korean PNH Registry.
Jun Ho JANG ; Jin Seok KIM ; Sung Soo YOON ; Je Hwan LEE ; Yeo Kyeoung KIM ; Deog Yeon JO ; Jooseop CHUNG ; Sang Kyun SOHN ; Jong Wook LEE
Journal of Korean Medical Science 2016;31(2):214-221
Paroxysmal nocturnal hemoglobinuria (PNH) is a progressive, systemic, life-threatening disease, characterized by chronic uncontrolled complement activation. A retrospective analysis of 301 Korean PNH patients who had not received eculizumab was performed to systematically identify the clinical symptoms and signs predictive of mortality. PNH patients with hemolysis (lactate dehydrogenase [LDH] > or = 1.5 x the upper limit of normal [ULN]) have a 4.8-fold higher mortality rate compared with the age- and sex-matched general population (P < 0.001). In contrast, patients with LDH < 1.5 x ULN have a similar mortality rate as the general population (P = 0.824). Thromboembolism (TE) (odds ratio [OR] 7.11; 95% confidence interval [CI] (3.052-16.562), renal impairment (OR, 2.953; 95% CI, 1.116-7.818) and PNH-cytopenia (OR, 2.547; 95% CI, 1.159-5.597) are independent risk factors for mortality, with mortality rates 14-fold (P < 0.001), 8-fold (P < 0.001), and 6.2-fold (P < 0.001) greater than that of the age- and sex-matched general population, respectively. The combination of hemolysis and 1 or more of the clinical symptoms such as abdominal pain, chest pain, or dyspnea, resulted in a much greater increased mortality rate when compared with patients with just the individual symptom alone or just hemolysis. Early identification of risk factors related to mortality is crucial for the management of PNH. This trial was registered at www.clinicaltrials.gov as NCT01224483.
Adolescent
;
Adult
;
Aged
;
Aged, 80 and over
;
Antibodies, Monoclonal/therapeutic use
;
Antibodies, Monoclonal, Humanized/therapeutic use
;
Area Under Curve
;
Child
;
Dyspnea/etiology
;
Female
;
Hemoglobinuria, Paroxysmal/*diagnosis/drug therapy/mortality
;
Hemolysis
;
Humans
;
Kaplan-Meier Estimate
;
Kidney Diseases/complications/diagnosis
;
L-Lactate Dehydrogenase/metabolism
;
Male
;
Middle Aged
;
Odds Ratio
;
ROC Curve
;
Registries
;
Republic of Korea
;
Retrospective Studies
;
Risk Factors
;
Thromboembolism/complications/diagnosis
;
Young Adult
8.Long-term Prognosis of Anti-Neutrophil Cytoplasmic Antibody-Negative Renal Vasculitis: Cohort Study in Korea.
Sung Woo LEE ; Mi Yeon YU ; Seon Ha BAEK ; Shin Young AHN ; Sejoong KIM ; Ki Young NA ; Dong Wan CHAE ; Ho Jun CHIN
Journal of Korean Medical Science 2016;31(4):542-546
Few studies have reported on the long-term prognosis of anti-neutrophil cytoplasmic antibody (ANCA)-negative renal vasculitis. Between April 2003 and December 2013, 48 patients were diagnosed with renal vasculitis. Their ANCA status was tested using indirect immunofluorescence and enzyme-linked immunosorbent assays. During a median (interquartile range) follow-up duration of 933.5 (257.5-2,079.0) days, 41.7% of patients progressed to end stage renal disease (ESRD) and 43.8% died from any cause. Of 48 patients, 6 and 42 were ANCA-negative and positive, respectively. The rate of ESRD within 3 months was higher in ANCA-negative patients than in ANCA-positive patients (P = 0.038). In Kaplan-Meier survival analysis, ANCA-negative patients showed shorter renal survival than did ANCA-positive patients (log-rank P = 0.033). In univariate Cox-proportional hazard regression analysis, ANCA-negative patients showed increased risk of ESRD, with a hazard ratio 3.190 (95% confidence interval, 1.028-9.895, P = 0.045). However, the effect of ANCA status on renal survival was not statistically significant in multivariate analysis. Finally, ANCA status did not significantly affect patient survival. In conclusion, long-term patient and renal survival of ANCA-negative renal vasculitis patients did not differ from those of ANCA-positive renal vasculitis patients. Therefore, different treatment strategy depending on ANCA status might be unnecessary.
Age Factors
;
Aged
;
Antibodies, Antineutrophil Cytoplasmic/*analysis
;
Cohort Studies
;
Enzyme-Linked Immunosorbent Assay
;
Female
;
Follow-Up Studies
;
Humans
;
Kaplan-Meier Estimate
;
Kidney Diseases/*diagnosis/mortality
;
Kidney Failure, Chronic/etiology
;
Male
;
Microscopy, Fluorescence
;
Middle Aged
;
Prognosis
;
Proportional Hazards Models
;
Republic of Korea
;
Retrospective Studies
;
Risk Factors
;
Severity of Illness Index
;
Sex Factors
;
Vasculitis/complications/*diagnosis/mortality
9.Ultrasound-guided open nephron sparing surgery without renal artery occlusion for central renal tumors.
Dian FU ; Ping LI ; Feng XU ; Feng TIAN ; Xiao-feng XU ; Zhi-feng WEI ; Zheng-yu ZHANG ; Jing-ping GE ; Wen CHENG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2016;36(1):118-120
From January 2008 to January 2013, 11 patients with central renal tumors underwent ultrasound-guided open nephron sparing surgery (ONSS) without renal artery occlusion. We removed the lesions, and the cut edges of the tumors were negative. Thus, we deduced that ultrasound-guided ONSS is suitable for the cases with obscure tumor boundary or multiple lesions. It could achieve the purpose of thoroughly removing lesions, as well as to expand the application range of nephron sparing surgery.
Arterial Occlusive Diseases
;
etiology
;
prevention & control
;
Carcinoma, Renal Cell
;
surgery
;
Female
;
Humans
;
Kidney Neoplasms
;
surgery
;
Male
;
Nephrons
;
surgery
;
Postoperative Complications
;
Renal Artery
;
pathology
;
surgery
;
Surgery, Computer-Assisted
;
adverse effects
;
methods
;
Ultrasonography
10.Peroxisome proliferator-activated receptor-γ agonist pioglitazone fails to attenuate renal fibrosis caused by unilateral ureteral obstruction in mice.
Ying ZHANG ; Jin WANG ; Qiao-dan ZHOU ; Cong-hui ZHANG ; Qing LI ; Shuai HUANG ; Juan ZHAN ; Kun WANG ; Yan-yan LIU ; Gang XU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2016;36(1):41-47
Renal tubulointerstitial fibrosis is the common ending of progressive renal disease. It is worth developing new ways to stop the progress of renal fibrosis. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have been studied to treat diabetic nephropathy, cisplatin-induced acute renal injury, ischemia reperfusion injury and adriamycin nephropathy. In this study, unilateral ureteral obstruction (UUO) was used to establish a different renal fibrosis model. PPAR? agonist pioglitazone was administrated by oral gavage and saline was used as control. At 7th and 14th day after the operation, mice were sacrificed for fibrosis test and T lymphocytes subsets test. Unexpectedly, through MASSON staining, immunohistochemistry for α-SMA, and Western blotting for a-SMA and PDGFR-β, we found that pioglitazone failed to attenuate renal fibrosis in UUO mice. However, flow cytometry showed that pioglitazone down-regulated Th1 cells, and up-regulated Th2 cells, Th17 cells and Treg cells. But the Th17/Treg ratio had no significant change by pioglitazone. Real-time PCR results showed that TGF-β and MCP-1 had no significant changes, at the same time, CD4(+) T cells associated cytokines were partially regulated by pioglitazone pretreatment. Taken together, pioglitazone failed to suppress renal fibrosis progression caused by UUO.
Animals
;
Chemokine CCL2
;
metabolism
;
Fibrosis
;
Kidney
;
pathology
;
Kidney Diseases
;
drug therapy
;
etiology
;
Male
;
Mice
;
Mice, Inbred C57BL
;
PPAR gamma
;
agonists
;
T-Lymphocyte Subsets
;
drug effects
;
Thiazolidinediones
;
administration & dosage
;
pharmacology
;
therapeutic use
;
Transforming Growth Factor beta
;
metabolism
;
Urethral Obstruction
;
complications

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