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Articles by H Zhu
Total Records ( 10 ) for H Zhu
  Y Zhang , L Bao , H Zhu , B Huang and H. Zhang

Leptospirosis renal disease is one of the common clinical manifestations of leptospirosis, including acute renal failure and tubulointerstitial nephritis. Outer membrane protein A-like protein Loa22 is a lipoprotein from Leptospira interrogans and has been suggested to be a corresponding virulence factor. However, the role of Loa22 in leptospiral nephropathy is not yet understood. In the present study, we constructed a vector and artificially expressed Loa22 in Escherichia coli BL21(DE)pLysS cells. After extensive purification, along with a GST tag protein control, Loa22 protein was used to test the cytotoxicity in cultured rat proximal tubule cells (NRK52E) and examine its effects on the induction of inflammatory responses. Using morphological examination, 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazoium hydrixide absorbance, lactate dehydrogenase assays and an analysis of apoptosis via flow cytometry, it was found that Loa22 protein mediates a direct cytotoxic effect on NRK52E cells in a dose-dependent manner. Using real-time PCR, western blotting and immunofluorescence, it was found that Loa22 protein upregulates the expression of toll-like receptor 2 (TLR2), induces nitric oxide synthase and promotes the production of nitric oxide (NO) and monocyte chemoattractant protein-1 (MCP-1) by NRK52E cells. Additionally, using a TLR2 blocking antibody, it was found that enhanced NO and MCP-1 production by NRK52E cells after Loa22 stimulation requires the activation of TLR2. Collectively, our data suggested that Loa22 is a critical virulence factor of L. interrogans and is involved in the leptospiral nephropathy through mediating direct cytotoxicity and enhancing inflammatory responses.

  B. S Peterson , M. N Potenza , Z Wang , H Zhu , A Martin , R Marsh , K. J Plessen and S. Yu

OBJECTIVE: The authors examined the effect of psychostimulants on brain activity in children and adolescents with ADHD performing the Stroop Color and Word Test. METHOD: The authors acquired 52 functional MRI scans in 16 youths with ADHD who were known responders to stimulant medication and 20 healthy comparison youths. Participants with ADHD were scanned on and off medication in a counterbalanced design, and comparison subjects were scanned once without medication. RESULTS: Stimulant medication significantly improved suppression of default-mode activity in the ventral anterior cingulate cortex in the ADHD group. When off medication, youths with ADHD were unable to suppress default-mode activity to the same degree as comparison subjects, whereas when on medication, they suppressed this activity to comparison group levels. Greater activation of the lateral prefrontal cortex when off medication predicted a greater reduction in ADHD symptoms when on medication. Granger causality analyses demonstrated that activity in the lateral prefrontal and ventral anterior cingulate cortices mutually influenced one another but that the influence of the ventral anterior cingulate cortex on the lateral prefrontal cortex was significantly reduced in youths with ADHD off medication relative to comparison subjects and increased significantly to normal levels when ADHD youths were on medication. CONCLUSIONS: Psychostimulants in youths with ADHD improved suppression of default-mode activity in the ventral anterior cingulate and posterior cingulate cortices, components of a circuit in which activity has been shown to correlate with the degree of mind-wandering during attentional tasks. Stimulants seem to improve symptoms in youths with ADHD by normalizing activity within this circuit and improving its functional interactions with the lateral prefrontal cortex.

  I Ivanov , R Bansal , X Hao , H Zhu , C Kellendonk , L Miller , J Sanchez Pena , A. M Miller , M. M Chakravarty , K Klahr , K Durkin , L. L Greenhill and B. S. Peterson

The role of the thalamus in the genesis of attention deficit hyperactivity disorder (ADHD) remains poorly understood. The authors used anatomical MRI to examine the morphology of the thalamus in youths with ADHD and healthy comparison youths.


The authors examined 46 youths with ADHD and 59 comparison youths 8–18 years of age in a cross-sectional case-control study. Conventional volumes and measures of surface morphology of the thalamus served as the main outcome measures.


A mixed-effects model comparing whole thalamic volumes revealed no significant differences between groups. Maps of the thalamic surface revealed significantly smaller regional volumes bilaterally in the pulvinar in youths with ADHD relative to comparison subjects. Post hoc analyses showed that ADHD patients who received stimulants (N=31) had larger conventional thalamic volumes than untreated youths with ADHD, and maps of the thalamic surface showed enlargement over the pulvinar in those receiving stimulants. Smaller regional volumes in the right lateral and left posterior thalamic surfaces were associated with more severe hyperactivity symptoms, whereas larger regional volumes in the right medial thalamic surfaces were associated with more severe symptoms of inattention.


These findings demonstrate reduced pulvinar volumes in youths with ADHD and indicate that this same area is relatively enlarged in patients treated with stimulants compared to those untreated. Associations of hyperactivity scores with smaller regional volumes on the lateral thalamic surface and inattention scores with larger regional volumes on the medial thalamic surface suggest the differential involvement of thalamic subcircuits in the pathogenesis of differing ADHD symptoms.

  H Zhu , D Hoppensteadt , O Iqbal , E Litinas , C Adiguzel and J. Fareed

The aim of this study was to compare the relative purity of bovine crude thrombin and its purified forms, namely, thrombin 4A and thrombin 4B (the products of King Pharma, Middleton, Wisconsin) by virtue of the detection of bovine prothrombin-related antigens in these preparations. Bovine prothrombin was administered intravenously to 3 individual rabbits on days 0, 21, 42, 91, 123, and 151 using standard immunologic method. Blood was drawn from each rabbit on days 30, 50, 105, 137, and 165, and the pooled antisera from 3 rabbits were purified to isolate immunoglobulin G (IgG) using protein G affinity columns. Using Western blotting method, serially diluted bovine crude thrombin, thrombin 4A, and 4B preparations were probed using the prothrombin IgGs obtained from each time point to explore prothrombin-related antigens in these preparations. The results revealed that compared with the prothrombin IgG collected on day 30, the IgGs collected on days 50 to 165 showed a time-dependent increase in their ability to detect the prothrombin-related antigens in 3 bovine thrombin preparations studied. The lowest amount of crude thrombin, thrombin 4A, and 4B preparations that prothrombin IgG could detect was 0.125, 10, and 20 U, respectively. The rank order of the number of immunoreactive bands detectable in 3 bovine thrombin preparations probed by the prothrombin IgGs collected from any given time point was always the same: crude thrombin > thrombin 4A > thrombin 4B. The results indicate that thrombin 4B preparation contains the least amount of antigens detectable by prothrombin IgG, suggesting that relatively thrombin 4B represents the most purified thrombin preparation among the 3 thrombin preparations studied.

  P Liu , W Chen , H Zhu , B Liu , S Song , W Shen , F Wang , S Tucker , B Zhong and D. Wang

The purpose of this study was to specifically investigate the clinicopathological role of expression of vascular endothelial growth factor-C (VEGF-C) as well as the correlation with clinical outcomes in esophageal squamous cell carcinomas (ESCCs).


Seventy-three patients with ESCC resected in our institute were included in this study. Formalin-fixed paraffin-embedded specimens were stained for VEGF-C and the correlation between the staining, its clinicopathological parameters and its prognostic power were analyzed statistically.


Of the 73 ESCC patients studied, 39 cases (53.4%) were strongly positive for VEGF-C. Six cases (8.2%) were negative and 28 cases (38.4%) revealed unclear weak reactions. All 34 cases were included in the negative group (46.6%). VEGF-C expression correlated with histological grade (P = 0.005), depth of tumor invasion (pT) (P = 0.021), lymph node metastasis (pN) (P = 0.002) and lymphatic invasion (P = 0.008). The median overall survival of 39 patients who had positive staining for tumor cell VEGF-C and 34 patients who had negative staining were 10.4 months (95% CI, 6.9–13.9 months) and 28.5 months (95% CI, 12.6–44.4 months), respectively (P = 0.003). In univariate analysis by log-rank test, histological grade, pN, stage, lymphatic invasion and VEGF-C were significant prognostic factors (P = 0.047, 0.007, 0.018, 0.002 and 0.003, respectively.). In multivariate analysis, high VEGF-C expression (P = 0.0451) maintained its independent prognostic influence on overall survival, as well as pN status (P = 0.0029).


Expression of VEGF-C is related to histological grade, pT, pN and lymphatic invasion, and is a prognostic indicator for ESCC.

  H Zhu , G. J Li , L Ding , X Cui , H Berg , S. M Assmann and Y. Xia

Heterotrimeric GTP-binding proteins, which consist of G, Gβ, and G subunits, play important roles in transducing extracellular signals perceived by cell surface receptors into intracellular physiological responses. In addition to a single prototypical G protein (GPA1), Arabidopsis has three unique G-like proteins, known as XLG1, XLG2, and XLG3, that have been found to be localized in nuclei, although their functions and mode of action remain largely unknown. Through a transcriptomic analysis, we found that XLG2 and XLG3 were rapidly induced by infection with the bacterial pathogen Pseudomonas syringae, whereas the XLG1 transcript level was not affected by pathogen infection. A reverse genetic screen revealed that the xlg2 loss-of-function mutation causes enhanced susceptibility to P. syringae. Transcriptome profiling revealed that the xlg2 mutation affects pathogen-triggered induction of a small set of defense-related genes. However, xlg1 and xlg3 mutants showed no difference from wild-type plants in resistance to P. syringae. In addition, the xlg2 xlg3 double mutant and the xlg1 xlg2 xlg3 triple mutant were not significantly different from the xlg2 single mutant in the disease resistance phenotype, suggesting that the roles of XLG1 and XLG3 in defense, if any, are less significant than for XLG2. Constitutive overexpression of XLG2 leads to the accumulation of abnormal transcripts from multiple defense-related genes. Through co-immunoprecipitation assays, XLG2 was found to interact with AGB1, the sole Gβ subunit in Arabidopsis, which has previously been found to be a positive regulator in resistance to necrotrophic fungal pathogens. However, no significant difference was found between three xlg single mutants, the xlg2 xlg3 double mutant, the xlg triple mutant, and wild-type plants in resistance to the necrotrophic fungal pathogens Botrytis cinerea or Alternaria brassicicola. These results suggest that XLG2 and AGB1 are components of a G-protein complex different from the prototypical heterotrimeric G-protein and may have distinct functions in modulating defense responses.

  R. A Dennis , H Zhu , P. M Kortebein , H. M Bush , J. F Harvey , D. H Sullivan and C. A. Peterson

A group (n = 8) of healthy older (68 ± 6 yr) adults participated in a 36-session progressive resistance exercise training program targeting the thigh muscles to determine the relationship between muscle gene expression and gains in muscle size and strength. Biopsies were obtained from the vastus lateralis at baseline 72 h after an acute bout of exercise and 72 h after completion of the training program. Training increased thigh muscle size (7%) and strength for the three exercises performed: knee extension (30%) and curl (28%) and leg press (20%). We quantified 18 transcripts encoding factors that function in inflammation, growth, and muscle remodeling that were demonstrated previously to be regulated by aging and acute exercise. The gain in extension strength and muscle size showed a high number of significant correlations with gene expression. These gains were most strongly correlated (P ≤ 0.003, R ≥ 0.89) with the baseline mRNA levels for insulin-like growth factor-1, matrix metalloproteinase-2 and its inhibitor TIMP1, and ciliary neurotrophic factor. Moreover, strength gains were inversely correlated with the change in these mRNA levels after training (P ≤ 0.002 and R ≤ –0.90). Changes in gene expression after acute exercise were not associated with training outcomes. These results suggest that higher baseline expression for key genes in muscle conveys an adaptive advantage for certain older adults. Individuals with lower baseline expression of these genes show less adaptation to exercise despite increased gene expression in response to training. These genes hold promise as useful predictors of training outcomes that could be used to design more effective exercise regimens for maintaining muscle function in older adults.

  X Kong , H Gan , Y Hao , C Cheng , J Jiang , Y Hong , J Yang , H Zhu , Y Chi , X Yun and J. Gu

CDK11p58, a CDK11 family Ser/Thr kinase, is a G2/M specific protein and contributed to regulation of cell cycle, transcription and apoptotic signal transduction. Recently, CDK11p58 has been reported to exert important functions in mitotic process, such as the regulation of bipolar spindle formation and sister chromatid cohesion. Here, we identified p21 activated kinase 1 (PAK1) as a new CDK11p58 substrate and we mapped a new phosphorylation site of Ser174 on PAK1. By mutagenesis, we created PAK1174A and PAK1174E, which mimic the dephosphorylated and phosphorylated form of PAK1; further analysis showed PAK1174E could be recruited to myosin V motor complex through binding to dynein light chain 2 (DLC2). PAK1174E could accelerate the mitosis progression in a nocodazole blocked cell model, while PAK1174A exhibited an opposite role. Our results indicated PAK1 may serve as a downstream effector of CDK11p58 during mitosis progression.

  Z Zheng , H Zhu , Q Wan , J Liu , Z Xiao , D. P Siderovski and Q. Du

Disrupting LGN’s function at lateral membrane domains displaces the axis of cell division in cyst-forming MDCK cells.

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