1.Curative Efficacy Analysis of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia with ASXL1 Mutation.
Ya-Jie SHI ; Xin-Sheng XIE ; Zhong-Xing JIANG ; Ding-Ming WAN ; Rong GUO ; Tao LI ; Xia ZHANG ; Xue LI ; Yu-Pei ZHANG ; Yue SU
Journal of Experimental Hematology 2025;33(3):720-725
OBJECTIVE:
To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation.
METHODS:
The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed.
RESULTS:
Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients.
CONCLUSION
Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans
;
Leukemia, Myeloid, Acute/therapy*
;
Hematopoietic Stem Cell Transplantation
;
Female
;
Male
;
Middle Aged
;
Mutation
;
Adult
;
Repressor Proteins/genetics*
;
Adolescent
;
Retrospective Studies
;
Aged
;
Nucleophosmin
;
Young Adult
;
Transplantation, Homologous
;
Prognosis
;
Survival Rate
2.Species identification of hard ticks and molecular survey of Ana plasma in partial areas of Anhui Province
Xue ZHAO ; Khakhane LERATO ; Wan-Qing LU ; Xin-Yun WU ; Fang-Fei SONG ; Yu XIN ; Ying-Ying ZHANG ; Chen XING ; Ke-Han XU ; Mao-Zhang HE ; Yan LIU
Chinese Journal of Zoonoses 2024;40(4):302-307
The distribution of Ixodes and Ana plasma carried by Ixodes ticks in Anhui Province was clarified as reference for prevention and control of anaplasmosis.In total,630 hard ticks were collected from Jinzhai County,Hanshan County,Jing-de County and Chaohu City in Anhui Province from April to August 2023.Ticks were identified by morphological analysis and 16S rRNA sequencing.Nested PCR with Anaplasma species-specific primers were used to detect 16S rRNA of Anaplasma spe-cies carried by ticks.A phylogenetic tree was constructed using MEGA11.0 software.Of the identified ticks,18.8%(18/96)were Rhipicephalus microplus and 81.2%(78/96)were Haemaphysalis longicorni in Jinzhai County of Anhui Province,all were H.longicorni in Hanshan County and Chaohu City,while the main species in Jingde County was R.microplus.The posi-tive rate of Anaplasma carried by H.longicornis was 30.9%(102/330),which included A.bovis at 1.8%(6/330),A.phagocytophilum at 21.8%(72/330)and uncultured Anaplasma species at 7.3%(24/330).R.microplus was positively cor-related to A.bovis(13.6%,18/132).The uncultured Anaplasma species was mainly detected in host-free ticks.A.phagocy-tophilum was detected in 24.4%of parasitic ticks and 15.8%of host-free ticks.The positive rates of host-free and parasitic ticks were 19.9%and 17.8%,respectively.These results show that H.longicornis and R.microplus were the dominant ticks in several counties of Anhui Province.H.longicornis and R.microplus as well as free and parasitic ticks all carried Anaplas-ma.
3. Research on ability of tetramethylpyrazine on promoting neurogenesis after OGD injury based on neural stem cell microenvironment
Wan-Qing XING ; Xiao-Xiong SONG ; Xue-Qing WANG ; Jin-Fu LU ; Gao-Hong LYU ; Bin YU ; Ming RUAN
Chinese Pharmacological Bulletin 2023;39(4):731-738
Aim To study the ability of tetramethylpyrazine (TMP) on promoting neurogenesis in neural stem cell microenvironment after oxygen-glucose deprivation (OGD) injury in vitro. Methods Neural stem cells (NSCs), astrocytes (ACs) and cerebral microvascular endothelial cells (BMECs) were respectively extracted and separated to establish a co-culture system. The OGD modeling conditions were optimized by NSCs activity, and the concentration of TMP was optimized by Nissl staining. Then CCK-8 and Nestin
4.Active components and mechanism of Jinwugutong Capsules in treatment of osteoporosis: a study based on UPLC-Q-Exactive-MS/MS combined with network pharmacology.
Xiao-Shuang YANG ; Xin-Li SONG ; Xue-Li SONG ; Ying-Yong YANG ; Wen LIU ; Sheng-Lei YANG ; Jia-Nan SHI ; Li SHEN ; Kai-Long WAN ; Xing-de LIU
China Journal of Chinese Materia Medica 2023;48(12):3360-3372
UPLC-Q-Exactive-MS/MS and network pharmacology were employed to preliminarily study the active components and mechanism of Jinwugutong Capsules in the treatment of osteoporosis. Firstly, UPLC-Q-Exactive-MS/MS was employed to characterize the chemical components of Jinwugutong Capsules, and network pharmacology was employed to establish the "drug-component-target-pathway-disease" network. The key targets and main active components were thus obtained. Secondly, AutoDock was used for the molecular docking between the main active components and key targets. Finally, the animal model of osteoporosis was established, and the effect of Jinwugutong Capsules on the expression of key targets including RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA). A total of 59 chemical components were identified from Jinwugutong Capsules, among which coryfolin, 8-prenylnaringenin, demethoxycurcumin, isobavachin, and genistein may be the main active components of Jinwugutong Capsules in treating osteoporosis. The topological analysis of the protein-protein interaction(PPI) network revealed 10 core targets such as AKT1, ALB, catenin beta 1(CTNNB1), TNF, and epidermal growth factor receptor(EGFR). The Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment showed that Jinwugutong Capsules mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, neuroactive ligand-receptor interaction, mitogen-activated protein kinase(MAPK) signaling pathway, Rap1 signaling pathway and so on. Molecular docking showed that the main active components of Jinwugutong Capsules well bound to the key targets. ELISA results showed that Jinwugutong Capsules down-regulated the protein levels of AKT1 and TNF-α and up-regulated the protein level of ALB, which preliminarily verified the reliability of network pharmacology. This study indicates that Jinwugutong Capsules may play a role in the treatment of osteoporosis through multiple components, targets, and pathways, which can provide reference for the further research.
Animals
;
Tumor Necrosis Factor-alpha/genetics*
;
Network Pharmacology
;
Capsules
;
Molecular Docking Simulation
;
Phosphatidylinositol 3-Kinases
;
Reproducibility of Results
;
Tandem Mass Spectrometry
5.Establishment of leukemia cell model with inducible AML1-ETO expression and its effect on fatty acid metabolism in leukemia cells.
Wan Qing XIE ; Xue YANG ; Run Xia GU ; Zheng TIAN ; Hai Yan XING ; Ke Jing TANG ; Qing RAO ; Shao Wei QIU ; Min WANG ; Jian Xiang WANG
Chinese Journal of Hematology 2023;44(5):366-372
Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.
Humans
;
U937 Cells
;
RUNX1 Translocation Partner 1 Protein
;
Leukemia/genetics*
;
Core Binding Factor Alpha 2 Subunit/genetics*
;
Oncogene Proteins, Fusion/genetics*
;
Leukemia, Myeloid, Acute/genetics*
6.Effect of pancreatic extracorporeal shock wave lithotripsy on chronic pancreatitis stones.
Wan Xing DUAN ; Wan Zhen WEI ; Xue YANG ; Qi GAO ; Jun CHEN ; Zheng WU ; Zheng WANG
Chinese Journal of Surgery 2023;61(7):590-595
Objective: To analyze the therapeutic effect and safety of pancreatic extracorporeal shock wave lithotripsy(P-ESWL) for patients with chronic pancreatitis complicated by stones of the pancreatic duct and to investigate the influencing factors. Methods: A retrospective analysis was performed on clinical data from 81 patients with chronic pancreatitis complicated by pancreatic duct calculus treated with P-ESWL in the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi 'an Jiaotong University from July 2019 to May 2022. There were 55 males(67.9%) and 26 females(32.1%). The age was (47±15)years (range: 17 to 77 years). The maximum diameter(M(IQR)) of the stone was 11.64(7.60) mm, and the CT value of the stone was 869 (571) HU. There were 32 patients (39.5%) with a single pancreatic duct stone and 49 patients(60.5%) with multiple pancreatic duct stones. The effectiveness, remission rate of abdominal pain, and complications of P-ESWL were evaluated. Student's t test, Mann Whitney U test, χ2 test, or Fisher's exact test was used to compare the characteristics between the effective and ineffective groups of lithotripsy. The factors influencing the effect of lithotripsy were analyzed by univariate and multivariate logistic regression analysis. Results: Eighty-one patients with chronic pancreatitis were treated with P-ESWL 144 times, with an average of 1.78 (95%CI:1.60 to 1.96) times per person. Among them, 38 patients(46.9%) were treated with endoscopy. There were 64 cases(79.0%) with effective removal of pancreatic duct calculi and 17 cases(21.0%) with ineffective removal. Of the 61 patients with chronic pancreatitis accompanied by abdominal pain, 52 cases(85.2%) had pain relief after lithotripsy. After lithotripsy treatment, 45 patients(55.6%) developed skin ecchymosis, 23 patients(28.4%) had sinus bradycardia, 3 patients(3.7%) had acute pancreatitis, 1 patient(1.2%) had a stone lesion, and 1 patient(1.2%) had a hepatic hematoma. Univariate and multivariate logistic regression analysis showed that the factors affecting the efficacy of lithotripsy included the age of patient(OR=0.92, 95%CI: 0.86 to 0.97), the maximum diameter of the stone(OR=1.12,95%CI:1.02 to 1.24) and the CT value of the stone(OR=1.44, 95%CI: 1.17 to 1.86). Conclusions: P-ESWL is effective in the treatment of patients with chronic pancreatitis complicated by calculi of the main pancreatic duct.Factors affecting the efficacy of lithotripsy include patient's age, maximum stone diameter, and CT value of calculi.
Male
;
Female
;
Humans
;
Retrospective Studies
;
Acute Disease
;
Treatment Outcome
;
Calculi/pathology*
;
Lithotripsy
;
Pancreatitis, Chronic/pathology*
;
Pancreatic Diseases/complications*
;
Pancreatic Ducts
;
Abdominal Pain/therapy*
7.Correlation study of abdominal aortic calcification and serum cell division cycle 42 in maintenance hemodialysis patients
Xue GONG ; Enbang LU ; Wenxiu XING ; Caixia REN ; Xiaona XU ; Meiyan WAN
Clinical Medicine of China 2022;38(2):170-177
Objective:To explore the correlation between abdominal aortic calcification and serum cell division cycle 42 (CDC-42) in maintenance hemodialysis (MHD) patients, and to explore the influencing factors of them.Methods:A cross-sectional study was conducted in the Blood Purification Center of Qingdao Municipal Hospital,112 patients who underwent MHD for more than 6 months from October 2019 to March 2021 were selected. The abdominal aortic calcification score (ACCs) was calculated by reference to the abdominal lateral X flat tablets. According to AACS, 50 cases were divided into no and mild calcification group (0≤AACS<5 points) and 62 cases were divided into moderate and severe calcification group (AACS≥5 points). The level of serum CDC-42 was detected by enzyme linked immunosorbent assay (ELISA). Taking the median serum CDC-42 level as the boundary, 56 cases were divided into low CDC-42 group and high CDC-42 group. Spearman correlation analysis was used to analyze the correlation between indicators. The risk factors of elevated CDC-42 and abdominal aortic calcification in MHD patients were explored by multivariate logistic regression analysis, and the variables were included by entry method.Results:In 112 patients, 91 cases (81.25%, 91/112) had abdominal aortic calcification, and the median serum CDC-42 level was 466.56 (335.56,623.57) ng/L. CDC-42, AACs, age, dialysis age, diabetic nephropathy, glycosylated hemoglobin, alkaline phosphatase, parathormone and calcium in the no and mild calcification groups were 347.77 (291.20, 419.53) ng/L, 1.00 (0.00, 3.00) points, (57.18±6.25) years, 31.50 (15.00, 49.25) months, 34.00%(17/50), (6.63±0.97)%, 116.22 (87.32, 152.13) U/L, 258.57 (143.40, 433.31) ng/L, (2.18±0.26) mmol/L, and in the moderate to severe calcification group were 602.69 (489.61, 762.73) ng/L, 10.00 (7.00, 16.25) points, (60.81±7.12) years, 49.00 (18.00, 67.00) months, 53.23%(33/62), (7.07±1.20)%, 144.34 (99.71, 201.76) U/L, 336.57 (230.63, 506.00) ng/L,(2.28±0.26) mmol/L, with statistically significant differences between the two groups(The statistical values were 6.99, 9.11, 2.83, 2.45, 4.14, 2.08, 2.04, 2.16 and 1.99, respectively, all P<0.05). CDC-42, AACs, glycosylated hemoglobin and parathormone in the low CDC-42 group were 336.50 (295.10, 395.25) ng/L, 2.00 (0.00, 4.00) points, (6.62±1.06) %, 250.60 (140.20, 462.02) ng/L,and in the high CDC-42 group were 622.92 (558.11, 836.65) ng/L, 10.00 (6.25, 15.75) points, (7.13±1.13) %, 347.21 (240.40,501.20) ng/L, with statistically significant differences between the two groups (The statistical values are 6.51, 5.21, 2.43 and 2.54, respectively,all P<0.05). Abdominal aortic calcification has positive correlations with CDC-42 ( r s=0.704, P<0.001), age ( r s=0.308, P=0.001), dialysis years ( r s=0.198, P=0.036), glycosylated hemoglobin ( r s=0.358, P<0.001), alkaline phosphatase ( r s=0.187, P=0.048), parathormone ( r s=0.437, P<0.001), serum calciu m( r s=0.323, P=0.001) and serum phospho-rus ( r s=0.251, P=0.007), and negative correlation with serum albumin( r s=-0.276, P=0.003). This study has confirmed that high serum CDC-42 ( OR=1.010, 95%CI:1.004-1.016, P=0.001) and senior dialysis age ( OR=1.033, 95%CI:1.006-1.061, P=0.018) were independent risk factors for moderate to severe abdominal aortic calcification.Serum CDC-42 levels has positive correlation with AACs ( r s=0.704, P<0.001), age ( r s=0.240, P=0.011), dialysis age ( r s=0.191, P=0.044), glycosylated hemoglobin ( r s=0.350, P<0.001), parathormone ( r s=0.380, P<0.001) and serum calcium ( r s=0.235, P=0.013). This study learned that,high AACs ( OR=1.185, 95%CI:1.037-1.354, P=0.013) and high parathormone ( OR=1.005, 95%CI:1.001-1.009, P=0.009) were independent risk factors for high CDC-42. The area under the receiver operating characteristic curve (ROC-AUC) of serum CDC-42 in predicting moderate and severe abdominal aortic calcification in MHD patients was 0.885. When the cut-off point was 466.56 ng/L, the predictive sensitivity and specificity were 79% and 86% respectively. Conclusion:The degree of abdominal aortic calcification in MHD patients was positively correlated with the level of serum CDC-42. High serum CDC-42 and high dialysis age were independent risk factors for abdominal aortic calcification in MHD patients. High AACS and high parathyroid hormone were independent risk factors for the increase of serum CDC-42 in MHD patients .
8.The effects of Mediterranean diet on cardiovascular risk factors in patients with type 2 diabetes: a Meta-analysis
Xing ZHENG ; Wenwen ZHANG ; Xiaojuan WAN ; Xiaoyan LYU ; Peng LIN ; Aijun WANG ; Shucheng SI ; Fuzhong XUE ; Yingjuan CAO
Chinese Journal of Practical Nursing 2022;38(18):1434-1441
Objective:To investigate the effect of Mediterranean diet on blood glucose control and cardiovascular risk factors in patients with type 2 diabetes.Methods:As to December 2021, the PubMed, Cochrance Central Register of Controlled Trials and Cochrance Database, Cochranc Library, Embase, China National Knowledge Infrastructure and Wanfang Medical Network system were searched for clinical randomized controlled trials(RCTs) of Mediterranean diet in patients with type 2 diabetes to conduct Meta-analysis The main observation index were cardiovascular risk factors, and the mean difference and its 95% confidence interval were used to estimate the effect size.Results:There were six RCTs, and 1181 patients met the inclusion criteria and entered the Meta-analysis. Compared with the control group, the intervention group can significantly reduce the level of systolic blood pressure ( MD=-1.20, 95% CI-2.21 to -0.19) and diastolic blood pressure ( MD=-4.17, 95% CI-7.12 to -1.22) in patients with type 2 diabetes mellitus, but there were no significant difference in the level of TC ( MD=2.92, 95% CI-0.84 to-6.67), HDL ( MD=2.33, 95% CI-0.27 to -4.92) and LDL ( MD=-2.34, 95% CI-5.67 to -0.99) between the two groups (all P>0.05). Conclusions:The meta-analysis provided evidence the Mediterranean diet showed the beneficial improvements in blood pressure glycemic control, but the effect of Mediterranean diet on lipid profile was not significant, which needed further verification.
9.Bioinformatics Analysis of the Influence of Coronavirus Infection on Hematopoietic System and Potential Intervention Drugs and Their Significance for COVID-19.
Jun-Dong ZHANG ; Bo YANG ; Hao-Ran CHEN ; Xiao-Hua CHI ; Xi-Meng CHEN ; Peng ZHI ; Hao-Min ZHANG ; Zi-Ning WANG ; Bin GUO ; Yi-Xing WANG ; Wan-Jun SUN ; Xue-Chun LU
Journal of Experimental Hematology 2021;29(3):975-982
OBJECTIVE:
To analyze and predict the effect of coronavirus infection on hematopoietic system and potential intervention drugs, and explore their significance for coronavirus disease 2019 (COVID-19).
METHODS:
The gene expression omnibus (GEO) database was used to screen the whole genome expression data related with coronavirus infection. The R language package was used for differential expression analysis and KEGG/GO enrichment analysis. The core genes were screened by PPI network analysis using STRING online analysis website. Then the self-developed apparent precision therapy prediction platform (EpiMed) was used to analyze diseases, drugs and related target genes.
RESULTS:
A database in accordance with the criteria was found, which was derived from SARS coronavirus. A total of 3606 differential genes were screened, including 2148 expression up-regulated genes and 1458 expression down-regulated genes. GO enrichment mainly related with viral infection, hematopoietic regulation, cell chemotaxis, platelet granule content secretion, immune activation, acute inflammation, etc. KEGG enrichment mainly related with hematopoietic function, coagulation cascade reaction, acute inflammation, immune reaction, etc. Ten core genes such as PTPRC, ICAM1, TIMP1, CXCR5, IL-1B, MYC, CR2, FSTL1, SOX1 and COL3A1 were screened by protein interaction network analysis. Ten drugs with potential intervention effects, including glucocorticoid, TNF-α inhibitor, salvia miltiorrhiza, sirolimus, licorice, red peony, famciclovir, cyclosporine A, houttuynia cordata, fluvastatin, etc. were screened by EpiMed plotform.
CONCLUSION
SARS coronavirus infection can affect the hematopoietic system by changing the expression of a series of genes. The potential intervention drugs screened on these grounds are of useful reference significance for the basic and clinical research of COVID-19.
COVID-19
;
Computational Biology
;
Follistatin-Related Proteins
;
Hematopoietic System
;
Humans
;
Pharmaceutical Preparations
;
SARS-CoV-2
10.Study on mechanism of Fangji Huangqi Decoction on hypouricemic effect and renal protection in hyperuricemia mice.
Xing WANG ; Ning XUE ; Li HONG-LEI ; Zhen CHEN ; Yu WAN
China Journal of Chinese Materia Medica 2020;45(21):5248-5255
The aim of this paper was to study the specific mechanism of Fangji Huangqi Decoction(FHT) in decreasing uric acid and improving renal function in mice with hyperuricemia(HUA) induced by potassium oxonate, so as to provide theoretical basis for the research and development of drugs for clinical prevention and treatment of HUA and the modernization of traditional Chinese medicine. Sixty Kunming male mice were randomly divided into 6 groups, with 10 mice in each group, namely normal group, model group(250 mg·kg~(-1) potassium oxonate), FHT high, medium and low-dose groups(10 920, 5 460, and 2 730 mg·kg~(-1)) and positive drug allopurinol group(5 mg·kg~(-1)). Drug administration was given once a day for 7 days. On the 6 th day, mice of each group were kept in metabolic cages, and their urine was collected for 24 hours for determination of uric acid, creatinine, and β2-microglobulin(β2-MG) levels. After 7 days, the animals were sacrificed to determine serum uric acid, creatinine β2-MG and interleukin-1β(IL-1β) levels, and their liver and kidney tissues were collected. The liver tissues were used for subsequent determination of xanthine oxidase(XOD) activity, and the kidney tissues were used for subsequent determination of IL-1β levels, pathological tests and related Western blot experiments. In the cell transfection experiment, the cells were divided into blank group, model group(4.8 mmol·L~(-1) uric acid treatment), FHT administration group(4.8 mmol·L~(-1) uric acid+200 μg·mL~(-1) FHT), leucine-rich repeat kinase 1(LRRK1)-small interfering RNA(siRNA) group(4.8 mmol·L~(-1) uric acid+LRRK1-siRNA transfection) and LRRK1-siRNA+FHT group(4.8 mmol·L~(-1) uric acid+LRRK1-siRNA transfection+200 μg·mL~(-1) FHT). After 24 h incubation, the level of IL-1β in the cell supernatant was detected, and the cellular proteins were extracted and used to determine LRRK1, epidermal growth factor receptor(EGFR), PDZ kinase 1(PDZK1) and nuclear factor-kappa B(NF-κB) protein expression levels. The results showed that, FHT could significantly reduce the uric acid, creatinine and β2-MG levels in serum and β2-MG levels in urine, increase the uric acid and creatinine levels in urine, and improve the renal pathological results of the HUA mice, but showed no effect on liver XOD activity; at the same time, we found that the expression level of IL-1β in serum and kidney, NF-κB, LRRK1 and EGFR protein levels in kidney of HUA mice were significantly increased, and the expression level of PDZK1 protein was significantly decreased, while FHT could significantly improve the abnormal expression of these proteins, and FHT increased protein expression of renal organic anion transporter 1(OAT1), OAT3 and ATP bin-ding transporter G2(ABCG2) in HUA mice, but FHT had no effect on the expression of urate transporter 1(URAT1). In the cell transfection experiment, after transfection of LRRK1-siRNA, the levels of IL-1β, EGFR and NF-κB in supernatant were significantly reduced, and the expression of PDZK1 protein was significantly increased. As compared with the LRRK1-siRNA group, the levels of IL-1β, EGFR, PDZK1 and NF-κB did not change significantly with the additional FHT. This study showed that FHT may regulate the renal uric acid transport system through LRRK1 gene, improve the capacity of uric acid excretion, so as to reduce the level of serum uric acid. At the same time, FHT can not only protect the kidney directly, but also in an indirect manner by reducing the level of uric acid.
Animals
;
Drugs, Chinese Herbal
;
Hyperuricemia/drug therapy*
;
Kidney
;
Male
;
Mice
;
Uric Acid

Result Analysis
Print
Save
E-mail