1.Endoplasmic reticulum stress participates in uric acid-induced phenotypic transformation of renal tubular epithelial cells
Pu WU ; Fei ZHAO ; Dan NIU ; Xinyang WANG ; Yaning HAO
Chinese Journal of Nephrology 2016;32(12):922-927
Objective To explore the effect of endoplasmic reticulum stress (ER stress) in uric acid?induced phenotypic change in renal tubular epithelial cells (HK?2). Methods (1) HK?2 cells were cultured with 0, 75, 150, 225, 300 mg/L uric acid for 24 h in vitro. (2) The cells were divided into normal control group, ER stress inhibitor 4?PBA (5 μmol/L) group, uric acid (150 mg/L) group and 4?PBA+uric acid group for 24 h. Morphological changes of HK?2 cells were observed under inverted microscope. MTT assay was used to detect the proliferation of HK?2 cells treated with 150 mg/L uric acid for 24, 48 and 72 h. The protein expressions of α?smooth muscle actin (α?SMA), vimentin, snail, glucose regulated protein 78 (GRP78) and the phosphorylation of eukaryotic initiation factor 2α(p?eIF2α) in HK?2 cells were measured by Western blotting. Results Compared with the control group, HK?2 cells in uric acid groups (150, 225, 300 mg/L) showed fibroblast?like appearance. The protein expressions of α?SMA, vimentin, snail, GRP78 and p?eIF2α in 150 mg/L and 225 mg/L uric acid groups were higher than those in the control group (all P<0.05). The proliferation of HK?2 cells in 150 mg/L uric acid group was lower than that in control group at 48 and 72 h (all P<0.01). Compared with the uric acid group, the cell morphology in 4?PBA+uric acid group was improved, and the protein expressions ofα?SMA, vimentin, snail, GRP78 and p?eIF2α were decreased (all P<0.05). Conclusions Uric acid may induce the phenotype transformation of renal tubular epithelial cell, and ER stress is involved. 4?PBA may inhibit the uric acid?induced ER stress response and phenotypic transformation, and may be beneficial in attenuating uric acid?induced renal tubular damage.
2.Bioinformatics analysis of microRNAs differently expressed in major depression disorder
Huimin FAN ; Wenbo WU ; Wei NIU ; Xinyang SUN ; Aifang ZHONG ; Lin ZHAO ; Liyi ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2015;24(5):418-422
Objective To predict the target genes and function of has-miR-26b,has-miR-1972,has-miR4485,has-miR-4498,and has-miR-4743 by bioinformatics analysis,and provide the theoretical basis for the further research.Methods The targets of the five microRNAs were predicted by Target Scan,miRBD,and DIANA-microT-CDS,and the result were analyzed by gene ontology and pathway analysis using FunNet.Results 734 predicted targets were obtained by finding the intersected genes of Target Scan,miRBD,and DIANA-microT-CDS.GO analysis showed that biological processes regulated by the differentially expressed microRNAs included diverse terms,among which some terms (e.g.,central nervous system development,neuron differentiation,axonogenesis,synaptic transmission,learning,and memory,etc.) had direct relationship with the central nervous system and brain functions.The pathway analysis showed that a significant enrichment in several pathways related to neuronal brain function,such as axon guidance,glutamatergic synapse,Wnt signaling pathway,mTOR signaling pathway,VEGF signaling pathway,etc.Among the five microRNAs,has-miR-26b,has-miR-1972,has-miR-4498 might have more important regulatory functions.Conclusion Bioinformatic analysis indicates that has-miR-26b,has-miR-1972,has-miR-4485,has-miR-4498,and has-miR-4743 are closely related to the mechanism and pathogenesis of major depressive disorder.
3.Diagnostic value of microRNAs in peripheral venous blood for patients with depressive disorder
Qiaoli ZHANG ; Huimin FAN ; Xinyang SUN ; Aifang ZHONG ; Lin ZHAO ; Wei NIU ; Liyi ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2015;24(11):1000-1004
Objective To investigate the diagnostic value of microRNA (miRNA) in peripheral venous blood for depressive disorder.Methods Real-time fluorescence quantitative PCR (RT-qPCR) was used to verify expression level of miRNAs in peripheral blood of non-specific mental retardation children,which were aberrantly expressed in depressive disorder patients,and then Receiver Operating Characteristics (ROC)curve was employed to confirm the sensitivity and specificity of abnormal miRNA expression in depressive disorder and non-specific mental retardation.Results MiR-1972,miR-26b,miR-4485,miR-4498 and miR-4743 were upregulated significantly in case group of depressive disorder(P<0.05),meanwhile miR-4485 and miR-4743 in aforementioned 5 miRNAs also upregulated significandy in patients of non-specific mental retardation(P<0.05),but miR-26b showed no significant difference between case group of non-specific mental retardation and the control group (P>0.05).The ROC curve of miR-26b in depressive disorder patients and their control group showed that the sensitivity and specificity were 0.609,0.664 respectively,and the area square under the curve was 0.614(P=0.021).The ROC curve of miR-26b in patients of depressive disorder and non-specific mental retardation indicated that the sensitivity and specificity were 0.784 and 0.471,and area square under the curve was 0.643 (P=0.003).Conclusion miR-26b probably have diagnostic value for depressive disorder,which may comorbidity with non-specific mental retardation.But genetic and psychosocial mechanism of comorbidity still needs further exploration.
4.Establishment of a rat model of laryngeal precancerous lesions induced by 4NQO smearing.
Jun Tao NIU ; Shu Guang LIU ; Ning JIANG ; Li WANG ; Chao LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2022;57(8):969-973
Objective: To establish a rat model for laryngeal precancerous lesions histologically and pathologically comparable to the human counterpart. Methods: Thirty-six Wistar rats were randomly divided into experimental group and control group, with 18 rats in each group, and 1% 4-nitroquinoline-1-oxide (4NQO) solution and saline were respectively applied to the laryngeal mucosas of rats in two groups. During subsequent 20 weeks, the changes of laryngeal mucosas were regularly observed with naked eyes and endoscope and lesions were determined by histology. SPSS 22.0 software was used for statistical analysis. Results: The food intake, water intake and body weight of the rats in the experimental group were lower than those in the control group, with statistically significant differences (all P<0.05). White plaque, superficial ulcer, erosion and miliary particles were present in the larynxes of rats in the experimental group, with histological manifestations of atypical hyperplasia or carcinoma in situ, and normal epitheliums were shown in the control group. The number of Ki67 positive cells in the laryngeal mucosas of rats in the experimental group at the 4 th, 8 th, 12 th, 16 th, and 20 th weeks were 13.5±2.4, 35.6±5.8, 53.4±8.3, 78.8±11.6, 80.6±12.4, respectively, no Ki67 positive cells were found in the control group at individual time points, and the differences were statistically significant (t=9.74, 10.63, 11.14, 11.77, 11.26, respectively, all P<0.01). Conclusion: 4NQO can credibly cause rats laryngeal precancerous lesions, which morphologically and histologically mimic laryngeal carcinnogenesis. This method is practical, easy and reliable to prepare the animal model of laryngeal precancerous lesions.
Animals
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Carcinoma in Situ
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Carcinoma, Squamous Cell/pathology*
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Humans
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Larynx/pathology*
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Precancerous Conditions/pathology*
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Rats
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Rats, Wistar
5.Six novel minimally invasive therapies for benign prostatic hyperplasia.
Journal of Zhejiang University. Medical sciences 2023;52(2):162-168
Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms in men. When drug treatment is ineffective or conventional surgery is not suitable, novel minimally invasive therapies can be considered. These include prostatic urethral lift, prostatic artery embolisation, water vapor thermal therapy, Aquablation-image guided robotic waterjet ablation, temporary implantable nitinol device and prostatic stents. These novel therapies can be performed in outpatient setting under local anesthesia, with shorter operative and recovery times, and better protection of ejaculatory function and erectile function. General conditions of the patient and advantages and disadvantages of the each of these therapies should be fully considered to make individualized plans.
Male
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Humans
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Prostatic Hyperplasia/complications*
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Stents/adverse effects*
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Embolization, Therapeutic/adverse effects*
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Lower Urinary Tract Symptoms/surgery*
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Treatment Outcome
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Minimally Invasive Surgical Procedures
6.Differential transcriptomic landscapes of multiple organs from SARS-CoV-2 early infected rhesus macaques.
Chun-Chun GAO ; Man LI ; Wei DENG ; Chun-Hui MA ; Yu-Sheng CHEN ; Yong-Qiao SUN ; Tingfu DU ; Qian-Lan LIU ; Wen-Jie LI ; Bing ZHANG ; Lihong SUN ; Si-Meng LIU ; Fengli LI ; Feifei QI ; Yajin QU ; Xinyang GE ; Jiangning LIU ; Peng WANG ; Yamei NIU ; Zhiyong LIANG ; Yong-Liang ZHAO ; Bo HUANG ; Xiao-Zhong PENG ; Ying YANG ; Chuan QIN ; Wei-Min TONG ; Yun-Gui YANG
Protein & Cell 2022;13(12):920-939
SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals
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COVID-19/genetics*
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Macaca mulatta
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SARS-CoV-2/genetics*
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Transcriptome