Papers by Shuangping Zhao
The Journal of cell biology, Jan 21, 2018
Vascular endothelial (VE)-cadherin forms homotypic adherens junctions (AJs) in the endothelium, w... more Vascular endothelial (VE)-cadherin forms homotypic adherens junctions (AJs) in the endothelium, whereas N-cadherin forms heterotypic adhesion between endothelial cells and surrounding vascular smooth muscle cells and pericytes. Here we addressed the question whether both cadherin adhesion complexes communicate through intracellular signaling and contribute to the integrity of the endothelial barrier. We demonstrated that deletion of N-cadherin () in either endothelial cells or pericytes increases junctional endothelial permeability in lung and brain secondary to reduced accumulation of VE-cadherin at AJs. N-cadherin functions by increasing the rate of VE-cadherin recruitment to AJs and induces the assembly of VE-cadherin junctions. We identified the dual Rac1/RhoA Rho guanine nucleotide exchange factor (GEF) Trio as a critical component of the N-cadherin adhesion complex, which activates both Rac1 and RhoA signaling pathways at AJs. Trio GEF1-mediated Rac1 activation induces the rec...
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Nephrology, 2015
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Brain Research, Mar 2, 2007
Activation of the caspase-dependent cell death pathways has been shown in focal seizures, but whe... more Activation of the caspase-dependent cell death pathways has been shown in focal seizures, but whether this occurs in prolonged generalized seizures is not known. We investigated whether the initiator caspase in the extrinsic pathway, caspase-8, or the intrinsic pathway, caspase-9, is activated during the first 24 h following lithium-pilocarpine-induced status epilepticus, when neuronal death is maximal and widespread. The thymuses of rats given methamphetamine were used as positive controls for caspase-3-activated cellular apoptosis. Following methamphetamine treatment, caspase-9 but not caspase-8 was activated in thymocytes. However, 6 or 24 h following status epilepticus, none of 26 brain regions studied showed either caspase-8 or -9 activation by immunohistochemistry, western blotting and enzyme activity assays. Our results provide evidence against the activation of the extrinsic and intrinsic caspase pathways in generalized seizures, which produce morphologically necrotic neurons with internucleosomal DNA cleavage (DNA laddering), a programmed process. In contrast, there is increasing evidence that caspase-independent programmed mechanisms play a prominent role in seizure-induced neuronal death.
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Zhongguo Wei Zhong Bing Ji Jiu Yi Xue Chinese Critical Care Medicine Zhongguo Weizhongbing Jijiuyixue, Sep 1, 2011
To observe the effects of adenovirus borne IΚB gene, an inhibitor of nuclear factor-ΚB (NF-ΚB), i... more To observe the effects of adenovirus borne IΚB gene, an inhibitor of nuclear factor-ΚB (NF-ΚB), infused via central vein, to treat infectious acute lung injury (ALI) in rats. According to random number table method, 30 pathogen-free Sprague-Dawley (SD) rats were randomly divided into three groups: sham group, ALI model group, IΚB gene treatment group, with 10 rats in each group. The rats of IΚB gene treatment group were infused 1 ml adenovirus borne IΚB gene (titre: 1×10(9)pfu ), the rats of sham group and ALI model group were infused 1 ml normal saline through central vein. Subsequently, the rats of ALI model group and the IΚB gene treatment group were given 1 ml lipopolysaccharide (LPS, 5 ml/kg) through tail vein to reproduce model of ALI. On the other hand, the rats of sham group were given 1 ml normal saline through tail vein. Blood gas analysis, the ratio of wet to dry weight (W/D) of lung, plasma contents of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and protein expression of NF-ΚBp65 in lung tissue were determined, the pathobiological changes in lung tissue were microscopically observed and the scores of lung injury were calculated after 7 days. The rats in three groups survived, except 1 rat died in ALI model group.Blood pH and partial pressure of arterial carbon dioxide (PaCO(2)) showed no obviously differences among three groups. Partial pressure of arterial oxygen (PaO(2) ) was highest in sham group and the lowest in ALI model group. The plasma content of TNF-α (μg/L) and IL-6 (ng/L ) in ALI model group were obviously higher than those in sham group (TNF-α: 5.20±1.09 vs. 3.01±0.46; IL-6: 540.28±100.78 vs. 214.45±61.37, both P<0.05). The plasma content of TNF-α and IL-6 in IΚB gene treatment group were obviously lower than those in ALI model group (TNF-α: 3.70±0.96 vs. 5.20±1.09, IL-6: 356.49±60.58 vs. 540.28±100.78, both P<0.05), and TNF-α content had restored to the level observed in sham group. The ratio of W/D of lung was lowest in sham group (4.49±0.36) and highest in ALI model group (5.78±0.43), and that of IΚB gene treatment group (5.33±0.38) was lower than that of ALI group. The score of lung injury was lowest in sham group (0.17±0.41) and highest in ALI model group (2.29±0.76), and that of IΚB gene treatment group (1.57±0.53) was lower than that of ALI group. The scale of NF-ΚBp65 immunohistochemistry was lowest in sham group (1.00±0.89) and highest in ALI model group (9.43±1.13), and that of IΚB gene treatment group (4.00±1.15) was lower than the latter. The differences of all the above parameters in three groups were statistically significant (all P<0.05 ). Increased expression of IΚB gene by an infusion of adenovirus borne IΚB gene through central vein can lower the levels of pro-inflammatory factors, such as TNF-α and IL-6, restrain the NF-ΚB activation, reduce lung water, alleviate alveolar collapse and lung consolidation in ALI in rats, thus lung injury is ameliorated.
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Pharmacology, Jan 8, 2015
A disintegrin and metalloproteinase (ADAM) 17, constitutively expressed in alveolar epithelium, i... more A disintegrin and metalloproteinase (ADAM) 17, constitutively expressed in alveolar epithelium, is the pivotal shedding enzyme mediating acute lung inflammation. On the other hand, angiotensin (Ang)-(1-7)/Mas signaling has been shown to improve acute respiratory distress syndrome and protect alveolar epithelial cells from apoptosis. In this study, we explored the effect of Ang-(1-7)/Mas signaling on the expression and activity of ADAM17 and assessed its impact on apoptosis in lipopolysaccharide (LPS)-treated human alveolar epithelial cells. LPS markedly induced the shedding activity of ADAM17 in alveolar epithelial cells, which was blocked by selective c-Jun N-terminal kinase (JNK) inhibitor SP600125. Ang-(1-7) concentration-dependently inhibited LPS-induced ADAM17 shedding activity, which was abolished by selective Mas blocker A779 and Mas shRNA. LPS and Ang-(1-7) showed no significant effect on the expression of ADAM17. Overexpression of ADAM17 synergized with LPS on increasing th...
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Journal of Neuroscience Research, 2010
We have shown that generalized seizures produce necrotic neurons with caspase-independent nuclear... more We have shown that generalized seizures produce necrotic neurons with caspase-independent nuclear pyknosis and DNA fragmentation. In this study, we determined the time course of translocation of mitochondrial cytochrome c, apoptosis-inducing factor, endonuclease G, lysosomal cathepsins B and D, and DNase II with respect to signs of irreversible neuronal damage. Adult male Wistar rats underwent lithium-pilocarpine-induced seizures lasting for 60 min, 3 hr, and 3 hr with 6- or 24-hr survival periods, after which the brains were prepared for immunofluorescence microscopic examination of piriform cortex. Contrary to expectation, cytochrome c and cathepsins B and D translocated to neuronal nuclei with DNase II, endonuclease G, and apoptosis-inducing factor within 60 min of seizure onset and persisted for 24 hr after 3-hr seizures. After 60-min seizures, some neurons showed translocation of the death-promoting proteins in normal-appearing neurons, prior to their appearance in irreversibly damaged neurons. Western blots of subcellular fractions of cytochrome c and cathepsins B and D confirmed their nuclear translocation. This is the first evidence of nuclear translocation of cathepsins B and D and the first in vivo evidence of nuclear translocation of cytochrome c. The appearance of these mitochondrial proteins and lysosomal enzymes before signs of irreversible neuronal death suggests that they could contribute to seizure-induced nuclear pyknosis and DNA fragmentation.
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IFMBE Proceedings, 2009
... Page 2. 1314 Shuang Zhao, Hexiang Wang, Yen Wah Tong ... [9] ZP Zhang, SH Lee, and SS Feng, F... more ... Page 2. 1314 Shuang Zhao, Hexiang Wang, Yen Wah Tong ... [9] ZP Zhang, SH Lee, and SS Feng, Folate-decorated poly(lactide-co-glycolide)-vitamin E TPGS nanoparticles for targeted drug deliv-ery, Biomaterials 28 (2007) 1889-1899. ...
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Relaxin 2000, 2001
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Relaxin 2000, 2001
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Theriogenology, 2015
Progesterone is an important steroid hormone in the regulation of the bovine estrous cycle. The s... more Progesterone is an important steroid hormone in the regulation of the bovine estrous cycle. The steroidogenic acute regulatory protein (StAR) is an indispensable component for transporting cholesterol to the inner mitochondrial membrane, which is one of the rate-limiting steps for progesterone synthesis. Low-density lipoprotein (LDL) supplies cholesterol precursors for progesterone formation, and the lysosomal degradation pathway of LDL is essential for progesterone biosynthesis in granulosa cells after ovulation. However, it is currently unknown how LDL and lysosomes coordinate the expression of the StAR gene and progesterone production in bovine granulosa cells. Here, we investigated the role of lysosomes in LDL-treated bovine granulosa cells. Our results reported that LDL induced expression of StAR messenger RNA and protein as well as expression of cholesterol side-chain cleavage cytochrome P-450 (CYP11A1) messenger RNA and progesterone production in cultured bovine granulosa cells. The number of lysosomes in the granulosa cells was also significantly increased by LDL; whereas the lysosomal inhibitor, chloroquine, strikingly abolished these LDL-induced effects. Our results indicate that LDL promotes StAR expression, synthesis of progesterone, and formation of lysosomes in bovine granulosa cells, and lysosomes participate in the process by releasing free cholesterol from hydrolyzed LDL.
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Desalination, 2014
ABSTRACT Forward osmosis (FO) is a novel membrane technology which has huge potential in the fiel... more ABSTRACT Forward osmosis (FO) is a novel membrane technology which has huge potential in the field of desalination and wastewater reclamation. Recoverable draw solutions (DS) with high osmotic pressure are crucial to FO process. This study investigated the water flux behavior of draw solutions formed by ammonium bicarbonate and eight soluble inorganic salts (K2SO4, NaCl, KCl, KNO3, NH4Cl, NH4NO3, urea and (NH4)2HPO4), respectively. A laboratory-scaled plate-and-frame FO setup with TFC FO membrane was used. The result indicated that the properties and water flux behavior of the aforementioned eight salt solutions were all enhanced after blended with NH4HCO3. Mixture of NH4Cl and NH4HCO3 exhibited the highest water flux when deionized water or simulated brackish water was used as feed solution (FS). Meanwhile, water flux of blended solution formed by urea and NH4HCO3 was the lowest. However, urea gained the highest water flux increase after blending with NH4HCO3. The osmotic driving force generated by draw solution in each FO process has not been utilized effectively no matter which kind of feed water was used. Moreover, the performance ratio (PR, experimental water flux divided by theoretical water flux) of most salt solutions decreased slightly after blending with NH4HCO3.
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Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences, 2010
To investigate the effect of 3 concentrations of sevoflurane pretreatment on acute lung injury in... more To investigate the effect of 3 concentrations of sevoflurane pretreatment on acute lung injury induced by endotoxin in rats. Thirty-six male SD rats were randomly divided into 6 groups:a control group(Group A), a sevoflurane group(Group B), a 3.6% sevoflurane pretreatment group(Group C), a 2.4% Sevoflurane pretreatment group(Group D), a 1.2% sevo sevoflurane pretreatment group(Group E), and lipopolysaccharide (Group F).The rats were killed 6 h after lipopolysaccharide (LPS) or saline injection.Histological examinations of the lung tissues were performed with light microscope. Lung wet/dry weight (W/D) ratio, myeloperoxidase (MPO) activity, and intercellular adhesion molecule-1 (ICAM-1) mRNA expression were assayed. Introvenous LPS significantly aggravated lung tissue damage,increased lung W/D ratio, MPO activity, and lung ICAM-1 mRNA expression compared with the control group(P<0.05). Precondition with 2.4% sevoflurane significantly attenuated the above-mentioned changes induced ...
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Plant biotechnology journal, Jan 28, 2015
Panicle architecture and seed size are important agronomic traits that directly determine grain y... more Panicle architecture and seed size are important agronomic traits that directly determine grain yield in rice (Oryza sativa L.). Although a number of key genes controlling panicle architecture and seed size have been cloned and characterized in recent years, their genetic and molecular mechanisms remain unclear. In this study, we identified a mutant that produced panicles with fascicled primary branching and reduced seeds in size. We isolated the underlying CLUSTERED PRIMARY BRANCH 1 (CPB1) gene, a new allele of DWARF11 (D11) encoding a cytochrome P450 protein involved in brassinosteroid (BR) biosynthesis pathway. Genetic transformation experiments confirmed that a His360Leu amino acid substitution residing in the highly conserved region of CPB1/D11 was responsible for the panicle architecture and seed size changes in the cpb1 mutants. Overexpression of CPB1/D11 under the background of cpb1 mutant not only rescued normal panicle architecture and plant height, but also had a larger l...
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Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences, 2012
To determine whether central venous-to-arterial carbon dioxide tension difference (Pcv-aCO(2)) co... more To determine whether central venous-to-arterial carbon dioxide tension difference (Pcv-aCO(2)) could still be used as a goal of fluid resuscitation in septic patients who already had ScvO2 greater than 70% after early resuscitation. A prospective observational study was performed on 56 septic patients admitted to the Intensive Care Unit (ICU) in a single University Hospital, who already had ScvO2 greater than 70% after early resuscitation. They were divided into two groups, based on whether the patients' initial Pcv-aCO2 was less than 6 mmHg (low gap group) or greater than or equal to 6 mmHg (high gap group). The following data were collected at 0, 12, and 24 hours (T(0), T(12), T(24)) after study inclusion: hemodynamic indices [mean blood pressure (MAP), heart rate (HR), cardiac output (CO), central venous pressure (CVP)], perfusion-related indexes [ScvO(2), Pcv-aCO2, serum lactate (Lac), Lac clearance rate], organ function- related indices [oxygenation index (PaO2/FiO(2)), ser...
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International Journal of Oncology, 2014
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Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences, 2011
To study the activation of Janus protein tyrosine kinase (JAK)/signal transducer and activator of... more To study the activation of Janus protein tyrosine kinase (JAK)/signal transducer and activator of transcription 1 (STAT1) signaling pathway and its inhibitor-signal transducer and activator of transcription-1(SOCS-1) in patients with systemic lupus erythematosus. A total of 45 patients with active systemic lupus erythematosus (SLE) and 30 healthy controls were randomly selected. Western blot was performed to measure the expression of Stat1 protein and phospho-Stat1 protein (an activated form of Stat1 protein) in the monocytes after stimulation with recombinant high mobility group box1 (rHMGB1) at various time points. Expression of Stat1 protein in the skin or lesional skin was also detected. Phasic expressions of SOCS-1 mRNA in the monocytes after rHMGB1 stimulation were detected by real-time reverse transcription-polymerase chain reaction. SOCS-1 gene expression in the skin or lesional skin was also detected. The expression level of Stat1 proteins in the monocytes from patients wit...
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Molecular Medicine Reports, 2014
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PLoS ONE, 2012
Critically ill patients with 2009 H1N1 influenza are often treated in intensive care units (ICUs)... more Critically ill patients with 2009 H1N1 influenza are often treated in intensive care units (ICUs), representing significant risk of nosocomial transmission to critical care clinicians and other patients. Despite a large body of literature and guidelines recommending infection control practices, numerous barriers have been identified in ICUs, leading to poor compliance to the use of personal protective equipment (PPE). The use of PPE among critical care clinicians has not been extensively evaluated, especially during the pandemic influenza. This study examined the knowledge, attitudes, and self-reported behaviors, and barriers to compliance with the use of PPE among ICU healthcare workers (HCWs) during the pandemic influenza. A survey instrument consisting of 36 questions was developed and mailed to all HCWs in 21 ICUs in 17 provinces in China. A total of 733 physicians, nurses, and other professionals were surveyed, and 650 (88.7%) were included in the analysis. Fifty-six percent of respondents reported having received training program of pandemic influenza before they cared for H1N1 patients, while 77% reported to have adequate knowledge of self and patient protection. Only 18% of respondents were able to correctly identify all components of PPE, and 55% reported high compliance (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;80%) with PPE use during patient care. In multivariate analysis, vaccination for 2009 H1N1 influenza, positive attitudes towards PPE use, organizational factors such as availability of PPE in ICU, and patient information of influenza precautions, as well as reprimand for noncompliance by the supervisors were associated with high compliance, whereas negative attitudes towards PPE use and violation of PPE use were independent predictors of low compliance. Knowledge and self-reported compliance to recommended PPE use among Chinese critical care clinicians is suboptimal. The perceived barriers should be addressed in order to close the significant gap between perception and knowledge or behavior.
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PLoS ONE, 2011
Approximately half of estrogen receptor (ER) positive breast tumors will fail to respond to endoc... more Approximately half of estrogen receptor (ER) positive breast tumors will fail to respond to endocrine therapy. Here we used an integrative bioinformatics approach to analyze three gene expression profiling data sets from breast tumors in an attempt to uncover underlying mechanisms contributing to the development of resistance and potential therapeutic strategies to counteract these mechanisms. Genes that are differentially expressed in tamoxifen resistant vs. sensitive breast tumors were identified from three different publically available microarray datasets. These differentially expressed (DE) genes were analyzed using gene function and gene set enrichment and examined in intrinsic subtypes of breast tumors. The Connectivity Map analysis was utilized to link gene expression profiles of tamoxifen resistant tumors to small molecules and validation studies were carried out in a tamoxifen resistant cell line. Despite little overlap in genes that are differentially expressed in tamoxifen resistant vs. sensitive tumors, a high degree of functional similarity was observed among the three datasets. Tamoxifen resistant tumors displayed enriched expression of genes related to cell cycle and proliferation, as well as elevated activity of E2F transcription factors, and were highly correlated with a Luminal intrinsic subtype. A number of small molecules, including phenothiazines, were found that induced a gene signature in breast cancer cell lines opposite to that found in tamoxifen resistant vs. sensitive tumors and the ability of phenothiazines to down-regulate cyclin E2 and inhibit proliferation of tamoxifen resistant breast cancer cells was validated. Our findings demonstrate that an integrated bioinformatics approach to analyze gene expression profiles from multiple breast tumor datasets can identify important biological pathways and potentially novel therapeutic options for tamoxifen-resistant breast cancers.
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Neuroscience Letters, 2010
We tested the hypothesis that mild insults produce apoptotic, and severe insults necrotic, cells ... more We tested the hypothesis that mild insults produce apoptotic, and severe insults necrotic, cells by subjecting adult Wistar rats to 60-min instead of 3-h generalized seizures. Rats&amp;amp;amp;amp;amp;amp;#39; brains were evaluated 6 and 24h later for evidence of neuronal necrosis by light and electron microscopy, the presence of TUNEL staining and active caspase-3 immunoreactivity, and for evidence of DNA laddering 24h after seizures. Apoptotic neurons from the retrosplenial cortex of postnatal day 8 rat pups served as positive controls. Six and 24h after seizures, 16 and 15 brain regions respectively out of 24 showed significant numbers of acidophilic neurons by hematoxylin and eosin stain. Three brain regions had significant numbers of TUNEL-positive neurons 24h after seizures. No neurons showed active caspase-3 immunoreactivity. Acidophilic neurons were necrotic by electron-microscopic examination. Ultrastructurally, they were shrunken and electron-dense, with shrunken, pyknotic nuclei and swollen mitochondria with disrupted cristae. Nuclei did not contain the irregular chromatin clumps found after 3-h seizures. None of the six brain regions studied ultrastructurally that show DNA laddering 24h after 3-h seizures showed DNA laddering 24h after 60-min seizures, probably because there were too few damaged neurons, although the lack of chromatin clumping might have been a contributing factor. Following seizures, a mild as well as a severe insult produces caspase-3-negative necrotic neurons. These results do not support the hypothesis that mild insults produce apoptotic, and severe insults, necrotic, cells.
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Papers by Shuangping Zhao