[Influence of acrylonitrile on morphology of testicle tissue in mice].
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Acrylonitrile↗
Biomedical subjects
Wei Xiao
Publications and source records attributed to Wei Xiao.
[Effect of Shenkangwan on mesangial cell NO and TGF-beta1 excretion in rats with early diabetic nephropathy].
OBJECTIVE: To study the mechanism of Shenkangwan (SKW) in treating early diabetic nephropathy (DN). METHODS: The effect of SKW on NO and transforming growth factor (TGF)-beta(1) production by the mesangial cells (MCs) of rats with early diabetic nephropathy was evaluated with serum pharmacological method. RESULTS: Compared with normal serum, the SKW-containing serum dose- and time-dependently inhibited TGF-beta(1) excretion and increased NO production in the MCs of rats with early DN (P<0.05 and P<0.01, respectively). CONCLUSION: The therapeutic effect of SKW on early DN may rely on the balance modulation of cytokine network by increasing NO production and decreasing TGF-beta(1) excretion to prevent cytokine-induced damage of the MCs.
Animals↗
[Renal protective effect of Shenkang pill on diabetic rats].
OBJECTIVE: To investigate the effects of Shenkang pill on renal function and extracellular matrix secretion on the diabetic rats. METHOD: The diabetic rat models were induced by intraperitoneal injection of streptozotocin (STZ) and randomly divided into 3 groups' model control group; Capoten group and Shenkangwan group. Some normal other rats were used as normal control group. All rats were treated with corresponding drugs for 8 weeks. During and after the treatment, the general state, blood and urine glucose levels, excretion rate of the 24 hour urine protein and albumin, serum creatinine and blood urea nitrogen contents, kidney weight and relative kidney weight were measured. The mRNA of fibronectin(FN) in the kidney also detected by semi-quantitative reverse transcription polymerase chain reaction(RT-PCR). RESULT: Diabetes mellitus and renal lesions occurred in the three model groups. The expression of FN mRNA of the kidney in diabetic rats increased obviously. Shenkang pill could improve the general state and renal function of the diabetic rats, decrease the blood glucose levels and the excretion rate of the 24 hour urine protein and albumin, reduce the expression of FN mRNA in kidney. CONCLUSION: Shenkang pill has a certain protective effect on the diabetic kidney.
Animals↗
[Effect of shenkangwan on TGF-beta1 and FN in rat mesangial cells cultured by high glucose].
OBJECTIVE: To investigate the effect of Shenkangwan on secretion of transforming growth factor-beta1 (TGF-beta1) and Fibronectin (FN) and their mRNA expression in rat mesangial cells (MC)cultured by high glucose and explore its molecule mechanism on treating diabetic nephropathy (DN). METHODS: Rat MC were cultured in vivo and divided into six groups: low glucose group, high glucose group, normal rat serum group, Capoten tablets group, Shenkangwan high dose group and low dose group. Seventy two hours later, the secretion of TGF-beta1 and FN in MC were detected by enzyme linked immunosorbent assay (ELISA). The expression of TGF-beta1, and FN mRNA were determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: High gluscose could induce secretion of TGF-beta1 and FN in MC and increase expression of TGF-beta1 and FN mRNA. While Shenkangwan could repress these effects. CONCLUSION: Shenkangwan can suppress the secretion of the extracellular matrix in MC via TGF-beta1 signal way.
Animals↗
Aplysamine-1 and related analogs as histamine H3 receptor antagonists.
Aplysamine-1 (1), a marine natural product, was synthesized and screened for in vitro activity at the human and rat histamine H3 receptors. Aplysamine-1 (1) was found to possess a high binding affinity for the human H3 receptor (Ki = 30+/-4 nM). Synthetic analogs of 1, including des-bromoaplysamine-1 (10) and dimethyl-{2-[4-(3-piperidin-1-yl-propoxy)-phenyl]-ethyl}-amine (13), were potent H3 antagonists.
Animals↗
Tumor-targeted therapy with a conditionally replicating mutant of HSV-1 induces regression of xenografted human hepatomas.
The selectively oncolytic effects of mtHSV, a HSV icp34.5 mutant with lacz gene insertion, on several tumor cells in vitro and its antitumor effects by the intratumoral (IT) route to nude mice loaded the human hepatoma xenografts were explored. The mtHSV could conditionally replicate in and lyse Hep-3B (human hepatoma cells), Hep-2 (human larynx cancer cells) and SPC-A1 (human lung cancer cells), but not MRC-5 (human fibroblast cells). The 125 nude mice loaded with Hep-3B were randomly divided into five treatment groups and given three IT injections with three different dose of the mtHSV, adriamycin (ADM), or vehicle (supernatant of non-infected Vero cells). Significant tumor growth inhibition (30%-70%) was seen in the nude mice treated IT with mtHSV, whereas tumors treated IT with Vero supernatant displayed rapid tumor growth. The results of regular and biochemical blood examination, systemic necropsy and pathological slices showed that mtHSV almost has no side effect on treated mice. RT-PCR results revealed that the replication of mtHSV was exclusively confined to the treated tumors, but not to other organs. Our results provide further preclinical evidence that mtHSV may be used as an oncolytic agent for cancer therapy.
Animals↗
Distinct regulation of Ubc13 functions by the two ubiquitin-conjugating enzyme variants Mms2 and Uev1A.
Ubc13, a ubiquitin-conjugating enzyme (Ubc), requires the presence of a Ubc variant (Uev) for polyubiquitination. Uevs, although resembling Ubc in sequence and structure, lack the active site cysteine residue and are catalytically inactive. The yeast Uev (Mms2) incites noncanonical Lys63-linked polyubiquitination by Ubc13, whereas the increased diversity of Uevs in higher eukaryotes suggests an unexpected complication in ubiquitination. In this study, we demonstrate that divergent activities of mammalian Ubc13 rely on its pairing with either of two Uevs, Uev1A or Mms2. Structurally, we demonstrate that Mms2 and Uev1A differentially modulate the length of Ubc13-mediated Lys63-linked polyubiquitin chains. Functionally, we describe that Ubc13-Mms2 is required for DNA damage repair but not nuclear factor kappaB (NF-kappaB) activation, whereas Ubc13-Uev1A is involved in NF-kappaB activation but not DNA repair. Our finding suggests a novel regulatory mechanism in which different Uevs direct Ubcs to diverse cellular processes through physical interaction and alternative polyubiquitination.
Amino Acid Sequence↗
Electrochemistry at conductor/insulator/electrolyte three-phase interlines: A thin layer model.
A thin layer model is proposed to assist in the understanding of the electrochemical conversion of insulator to conductor at the conductor/insulator/electrolyte three-phase interline (3PI) when the influence of mass diffusion in the electrolyte phase is negligible. The model predicts, under potentiostatic conditions, a linear variation of the current or the length of the 3PI with time. When polarization is sufficiently large, the logarithm of the current/time ratio or the 3PI-length/time ratio, according to the model, increases linearly with the applied potential. These predictions were tested against and agreed very well with two practical systems: the electroreduction of solid AgCl to Ag in aqueous KCl and of solid SiO2 to Si in molten CaCl2. Kinetic parameters were derived from experimental data using the model. Particularly, the electron transfer coefficient, alpha, was found to be about 0.29 for the reduction of AgCl to Ag in the aqueous KCl solution at room temperature but about 10(-2) for the reduction of SiO2 to Si in molten CaCl2 at 850 degrees C.
Journal Article↗
4-phenoxypiperidines: potent, conformationally restricted, non-imidazole histamine H3 antagonists.
Two new series of 4-(1-alkyl-piperidin-4-yloxy)-benzonitriles and 4-(1-isopropyl-piperidin-4-yloxy)-benzylamines have been prepared. In vitro activity was determined at the recombinant human H(3) receptor and several members of these new series were found to be potent H(3) antagonists. The present compounds contain a 4-phenoxypiperidine core, which behaves as a conformationally restricted version of the 3-amino-1-propanol moiety common to the many previously described non-imidazole histamine H(3) ligands. One selected member of the new series, 4-[4-(1-isopropyl-piperidin-4-yloxy)-benzyl]-morpholine (13g), was found to be a potent, highly selective H(3) receptor antagonist with in vivo efficacy in a rat EEG model of wakefulness at doses as low as 1 mg/kg sc.
Animals↗
A single Mms2 "key" residue insertion into a Ubc13 pocket determines the interface specificity of a human Lys63 ubiquitin conjugation complex.
Human Ubc13 and Mms2 (or its homolog, Uev1) form a unique ubiquitin-conjugating enzyme (Ubc) complex that generates atypical Lys(63)-linked ubiquitin conjugates. Such conjugates are attached to specific targets that modulate the activity of various cellular processes including DNA repair, mitotic progression, and nuclear factor-kappaB signaling. Whereas Ubc13 is a typical Ubc, Mms2 is a non-catalytic Ubc variant. Substantial biochemical evidence has revealed a mechanism whereby Mms2 properly orients ubiquitin to allow for Lys(63) conjugation by Ubc13; however, how this specific Ubc13-Mms2 complex is formed and why Mms2 does not form a complex with other Ubcs have not been reported. In order to address these questions, we used a structure-based approach to design mutations and characterize the human Ubc13-Mms2 interface. We used the yeast two-hybrid assay, glutathione S-transferase pull-downs, and surface plasmon resonance to test in vivo and in vitro binding. These experiments were paired with functional complementation and ubiquitin conjugation studies to provide in vivo and in vitro functional data. The results in this study allowed us to identify important residues of the Ubc13-Mms2 interface, determine a correlation between heterodimer formation and function, and conclude why Mms2 forms a specific complex with Ubc13 but not other Ubc proteins.
Amino Acid Sequence↗
Matrix metalloproteinases-2, -9 and tissue inhibitor of metallo-proteinase-1 in lung cancer invasion and metastasis.
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DNA, Complementary↗
Involvement of human natural killer cells in asthma pathogenesis: natural killer 2 cells in type 2 cytokine predominance.
BACKGROUND: T H 2 cells play a pivotal role in the pathogenesis of human asthma. Natural killer (NK) cells are also thought to divide into NK1 and NK2 subsets. OBJECTIVE: Whether NK1 or NK2 cells are involved in asthma remains unclear. METHODS: Triple-color flow cytometry for detecting intracellular cytokine and NK cell surface phenotype from asthmatic patients was used. The NK cell cloning and analysis with RT-PCR for cytokine expression and Western blotting for signal transducer and activator of transcription activation were performed. RESULTS: For the first time, we observed that the ratio of IL-4 + CD56 + NK2 cells in PBMCs of 8 asthmatic patients were higher than in healthy individuals. NK cell clones were then obtained by means of limited dilution, and the average mean of the relative intensity of PCR products for type 2 cytokines significantly increased in the asthmatic patients. Signal transducer and activator of transcription 6, a key transcript factor of type 2 phenotype, was constitutively activated in NK2 clones from asthmatic patients. We cocultured freshly purified NK cells from asthmatic patients with IFN-gamma and anti-IL-4 antibody in the presence of IL-15 and found that the content of IL-4 + NK2 cells significantly decreased after treatment. Interestingly, NK2-biased status in asthmatic patients was reversed when patients recovered from regular therapy. CONCLUSION: The results suggest that the NK2 cell subset is involved in the pathogenesis of asthma.
Adolescent↗
Molecular basis of ataxia telangiectasia and related diseases.
Ataxia telangiectasia (AT) is a rare human disease characterized by extreme cellular sensitivity to radiation and a predisposition to cancer, with a hallmark of onset in early childhood. Several human diseases also share similar symptoms with AT albeit with different degrees of severity and different associated disorders. While all AT patients contain mutations in the AT-mutated gene (ATM), most other AT-like disorders are defective in genes encoding an MRN protein complex consisting of Mre11, Rad50 and Nbs1. Both ATM and MRN function as cellular sensors to DNA double-strand breaks, which lead to the recruitment and phosphorylation of an array of substrate proteins involved in DNA repair, apoptosis and cell-cycle checkpoints, as well as gene regulation, translation initiation and telomere maintenance. ATM is a member of the family of phosphatidylinositol 3-kinase-like protein kinases (PIKK), and the discovery of many ATM substrates provides the underlying mechanisms of heterologous symptoms among AT patients. This review article focuses on recent findings related to the initial recognition of double-strand breaks by ATM and MRN, as well as a DNA-dependent protein kinase complex consisting of the heterodimer Ku70/Ku80 and its catalytic subunit DNA-PKcs, another member of PIKK. This possible interaction suggests that a much greater complex is involved in sensing, transducing and co-ordinating cellular events in response to genome instability.
Acid Anhydride Hydrolases↗
Sputum cathelicidin, urokinase plasminogen activation system components, and cytokines discriminate cystic fibrosis, COPD, and asthma inflammation.
BACKGROUND: Interest in airways inflammatory disease has increasingly focused on innate immunity. We investigated several components of innate immunity in induced sputum of patients with cystic fibrosis (CF), COPD, and asthma, and healthy control subjects. METHODS: Twenty eight patients with mild CF lung disease (age > or = 12 years; FEV1, 74 +/- 3% predicted [mean +/- SE]), 74 adults with COPD (FEV1, 55 +/- 2% of predicted), 34 adults with persistent asthma (FEV1, 66 +/- 2% of predicted), and 44 adult control subjects (FEV1, 85 +/- 1% of predicted) were studied while in stable clinical condition. Levels of sputum interleukin (IL)-8, IL-10, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, human cationic antimicrobial protein 18 (CAP18), urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1 were determined. Cell sources were investigated by flow cytometry and immunohistochemistry. Spirometry was performed prior to sputum induction. RESULTS: CF patient sputum showed greatest increase in IL-8 compared to that of patients with COPD and asthma (which were also greater than control subjects), and elevated levels of TNF-alpha and IL-10 compared to other groups. There were no differences in IFN-gamma. CAP18 levels were elevated in CF and COPD patients compared to control subjects, while asthma patients had reduced CAP18 levels. uPA levels were similar but uPAR was elevated in CF and COPD patients more so than in asthma patients, while PAI-1 levels were elevated in all three disease groups. CAP18 localized to neutrophil secondary granules; neutrophils were also sources of IL-8 and PAI-1. CAP18 and PAI-1 negatively correlated with pulmonary function. CONCLUSION: Induced-sputum innate immune factor levels discriminate inflammatory changes in CF, COPD, and asthma, suggesting potential roles in pathophysiology and as well as providing disease-specific biomarker patterns.
Adolescent↗
Differentially expressed genes associated with human lung cancer.
To investigate the gene expression of 9 cDNA clones generated by suppression subtraction hybridization (SSH), Northern blot analysis was performed on a panel of immortalized bronchial epithelial cell lines, lung cancer cell lines and normal human bronchial epithelial cells (HBEC). The clones were located on chromosomes 1q, 2q, 3p, 3q, 4q and 14q representing regions that are frequently affected by DNA imbalances as shown by comparative genomic hybridization (CGH). Two were unknown (H24, H103) whereas the others matched to the Pest-containing nuclear protein (H52), Rp11-767C1 gene (H134), the hypothetical gene AK025444 (H238), Guanine nucleotide binding protein (G protein)/alpha inhibiting activity polypeptide 2 (H268), Laminin gamma 1 (Y45), the DEAD (Asp-Glu-Ala-Asp/His) box polypeptide 9 (Y162) and the heat shock 90 kDa protein 1, alpha (Y238). Northern blot results indicated that all of the studied clones showed differential up- or down-regulation in immortalized cells and lung cancer cell lines. Of those, clone Y238 representing HSP90alpha showed a clearly over-expressed transcript. Subsequently, semi-quantitative RT-PCR was used to further confirm the over-expression of Y238, indicating that HSP90alpha was significantly over-represented in 49 primary lung tumors as compared to 14 normal lung samples (P<0.01). CGH showed that the majority of studied lung cancer cell lines (71.4%) carried an overrepresentation at 14q32 where HSP90alpha is located suggesting that it may be affected by DNA copy number changes. The further characterization of these clones will provide us with valuable information on its role in lung carcinogenesis and may help to develop new diagnostic or therapeutic targets for this lethal disease.
Blotting, Northern↗
Subcellular localization of caspase-3 activation correlates with changes in apoptotic morphology in MOLT-4 leukemia cells exposed to X-ray irradiation.
Caspase-3 is a critical effector caspase for apoptosis, which cleaves proteins, including cytoskeletal and associated proteins, kinases, and members of the Bcl-2 family of apoptosis-related proteins. This leads to changes in apoptotic morphology, such as membrane externalization and cytoplasm and nuclear condensation. It has been reported that pro-caspase-3 is activated in the cytosol. However, it remains obscure how caspase-3 activation correlates to serial changes in cell morphology during apoptosis. The current study was therefore undertaken to assess the relationship between caspase-3 activation and its subcellular localization and alterations in apoptotic morphology in MOLT-4 human leukemia cells exposed to X-ray irradiation. Fluorescence labeled inhibitor of caspases (FLICA) was used to detect caspase-3 activity in apoptotic cells in this project; cell morphology and caspase-3 sub-localization were determined by confocal microscopy. Our data showed that MOLT-4 cells presented typical morphological changes in apoptosis, such as membrane reversion, DNA fragmentation, and formation of apoptotic cell bodies following 10 Gray (Gy) of X-ray irradiation. Caspase-3 was activated 2 h after X-ray irradiation, and its activity increased markedly after 4-6-h exposure. Membrane reversion in MOLT-4 leukemia cells was detected by Annexin V assay at 4 h following X-ray irradiation, 2 h after the elevated caspase-3 activity was measured. Cytologically, activation of caspase-3 was first observed close to the inside surface of the cellular membrane, then transferred to the cytoplasm, and finally translocated to the nuclear region. We conclude that caspase-3 is activated in MOLT-4 cells following exposure to X-rays, and that the enhanced caspase-3 activity and its sub-localization shifting is correlated to changes in apoptotic morphology. The spatial shift of activated caspase-3 in X-ray-induced apoptotic MOLT-4 leukemia cells is a process of crucial importance for apoptosis.
Apoptosis↗
[Effect of the Yifuning soft gelatin capsules on estrogen receptor and nitric oxide levels in ovariectomized rats].
OBJECTIVE: To investigate the effects of the Yifuning soft gelatin capsules(YFN)on estrogen receptor (ER) and nitric oxide (NO) levels in ovariectomized rats. METHOD: Fifty female mature sprague-dawley rats were randomly divided into 5 groups: normal control; model control; diethylstilbestrol tablets (DT); YFN (high dose and low dose). After 4 weeks' treatment, the serum E2 levels were detected by radioimmunoassay. The estrogen receptor (ER) levels of uterus and artery were detected with method of radioligand binding assay of receptor (RBAR). The uterus pathologic changes were investigated with light microscope. NO and NOS levels of the artery and the uterus index were detected too. RESULT: YFN can obviously improve serum E2, increase index and ER of uterus (P < 0.01 or P < 0.05), and ameliorate the uterus' pathologic changes in OVX rats. It also can increase the artery' ER, NO and NOS levels. CONCLUSION: YFN can cure the climacteric syndrome and prevent the cardiovascular disease after post-menopause.
Animals↗
Enhanced TRAIL sensitivity by E1A expression in human cancer and normal cell lines: inhibition by adenovirus E1B19K and E3 proteins.
TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily of cytokines that induces apoptosis in a variety of cancer cells, but not in normal cells. However, more and more tumor cells remain resistant to TRAIL, which limited its application for cancer therapy. Expression of the adenovirus serotype 5 (Ad5) E1A sensitizes tumor cells to apoptosis by TNF-alpha, Fas-ligand, and TRAIL. Here we asked whether E1A overcomes this resistance and enhances TRAIL-induced apoptosis in the tumor cells. Our results revealed that the tumor cell lines, HeLa and HepG2, with infection by Ad-E1A, were highly sensitive to TRAIL-induced apoptosis. Importantly, we found that in normal primary human lung fibroblast cells (HLF) TRAIL is capable of inducing apoptosis in combination with E1A as efficiently as in some tumor cell lines. The adenovirus type 5 encoding proteins, E1B19K and E3 gene products, have been shown to inhibit E1A and TRAIL-induced apoptosis of HLF cells by using the recombinant adenovirus AdDeltaE1B55K, with mutation of E1B55K, containing E1B19K and complete E3 region. Further results demonstrated that the expression of DR5 and TRAIL was down-regulated in the AdDeltaE1B55K co-infected HLF cells. These findings suggest that TRAIL may play an important role in limiting virus infections and the ability of adenovirus to inhibit killing may prolong acute and persistent infections. The results from this study have also suggested the possibility that the combination of E1A with TRAIL could be used in the treatment of human malignancy, or in the selection of the optimal adenovirus mutant as effective delivering vector for cancer therapy.
Adaptor Proteins, Signal Transducing↗