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Biomedical subjects

Yong Yang

Publications and source records attributed to Yong Yang.

At least 73 records · Page 4Linked to original sources

Protein phosphatase activity of PTEN inhibited the invasion of glioma cells with epidermal growth factor receptor mutation type III expression.

PTEN is a major tumor suppressor gene that has been shown to inhibit cell invasion. Its mutation has been found in 20-40% of malignant gliomas. Meanwhile, the type III EGFR mutation (EGFRvIII), which was frequently found in gliomas, promoted cell invasion. In the present study, the effects of PTEN on cell invasion were investigated in U87DeltaEGFR glioblastoma cells with EGFRvIII expression but missing PTEN. The cell invasion was downregulated by transfection of phosphatase-active forms of PTEN (wild-type and G129E) but not by PTEN (C124A) with an inactive phosphatase domain; the effects were correlated with decreased tyrosine phosphatase levels of FAK at Tyr397, which was increased by EGFRvIII. Overexpression of FAK mutant (Y397F) could partially mimic the effect of PTEN on cell invasion. Although EGFRvIII increased the levels of P-Akt and PTEN eliminated it, PI-3K inhibitors, wortmannin or Ly294002, could not decrease the cell invasion. In conclusion, PTEN could inhibit cell invasion even in the presence of the constitutively active EGFR; this inhibition depended on its protein phosphatase activity, partially by dephosphorylating FAK, but not depended on its lipid phosphatase activity.

Cell Line, Tumor↗

Localization of NGF and TrkA at mitotic apparatus in human glioma cell line U251.

It has previously been implicated that nerve growth factor (NGF) with its high-affinity receptor tyrosine kinase A (TrkA) could play an important role in the growth modulation of human tumor cells, such as glioblastoma multiform cell lines and human breast cancer cell lines. However, the direct mitogenic effects of NGF and TrkA in these tumor cells still remain to be elucidated. Herein we show, by immunofluorescence staining, that NGF was colocalized with gamma-tubulin at the centrosomes or the spindle poles throughout the cell cycle and phosphorylated TrkA was colocalized with alpha-tubulin at mitotic spindle in the glioma cell line U251. The results suggest that NGF concentrated to centrosome can recruit its receptor TrkA there and cause phosphorylation of the latter. The phosphorylated TrkA with the tyrosine kinase activity may phosphorylate the tubulin and promote the mitotic spindle assembly. By these mechanisms, NGF can modulate the mitosis of human glioma cells.

Cell Line, Tumor↗

The regulation of rotenone-induced inflammatory factor production by ATP-sensitive potassium channel expressed in BV-2 cells.

Our previous studies have demonstrated that activating ATP-sensitive potassium channel (K(ATP) channel), not only improved Parkinsonian behavior and neurochemical symptoms, but also reduced iNOS activity and mRNA levels in striatum and nigra of rotenone rat model of Parkinson's disease (PD). In this study, it was first shown that the subunits of K(ATP) channels are expressed in BV-2 cells, and then it was investigated whether K(ATP) channel was involved in regulating inflammatory factor production from BV-2 cells activated by rotenone. It was found that K(ATP) channel was expressed in BV-2 cell and formed by the combination of Kir 6.1 and SUR 2A/2B. K(ATP) channel openers (KCOs) including pinacidil, diazoxide and iptakalim (Ipt) exerted beneficial effects on rotenone-induced morphological alterations of BV-2 cells, decreased tumor necrosis factor alpha (TNF-alpha) production and the expression and activity of inducible isoform of nitric oxide synthase (iNOS). Either glibenclamide or 5-hydroxydecanoate acid (a selective mitochondrial K(ATP) channel blocker) could abolish the effects of KCOs, suggesting that K(ATP) channels, especially mitochondrial ATP-sensitive potassium channels (mitoK(ATP) channels), played a crucial role in preventing the activation of BV-2 cells, and subsequently the production of a variety of proinflammatory factors. Therefore, activation of K(ATP) channel might be a new therapeutic strategy for treating neuroinflammatory and neurodegenerative disorders.

ATP-Binding Cassette Transporters↗

Photoselective vaporization of the prostate in the treatment of benign prostatic hyperplasia.

BACKGROUND: The treatment of symptomatic benign prostatic hyperplasia (BPH) remains a challenge for most urologic surgeons. We studied a cumulative cohort of patients with symptomatic benign prostatic hyperplasia (BPH) who underwent photoselective vaporization of the prostate (PVP) and evaluated the efficacy and safety of this procedure. METHODS: A total of 196 patients with lower urinary tract obstruction symptoms secondary to BPH were treated using laser vaporization of the prostate under sacral canal anesthesia at our institutions. The therapeutic results were assessed using following variables: the safety and efficacy of sacral anesthesia, blood loss, operative time, indwelling catheterization. Preoperative and perioperative parameters were evaluated in the international prostate symptom score (IPSS), quality of life score (QoL), maximal urinary flow rate (Qmax), post-void residual urine volume (PVR) and the change of sexual function. Patients were also assessed for 3-month follow up. RESULTS: PVP was performed successfully for all patients. There were 195 patients under sacral anesthesia and 1 patient under epidural anesthesia. Mean operative time was (45.2 +/- 18.5) minutes. The mean IPSS decreased from (26.6 +/- 3.2) to (5.6 +/- 1.4) and the QoL score decreased from (5.7 +/- 0.4) to (1.6 +/- 0.5), respectively (P < 0.05), while mean Qmax increased from (6.7 +/- 2.5) ml/s preoperatively to (19.6 +/- 2.4) ml/s, PVR decreased from 158.4 to 25.8 ml, respectively (P < 0.05). Average catheterization time was (1.8 +/- 0.9) days. There was no significant blood loss or fluid absorption during the period of PVP. Complications consisted of transient dysuria in 3 patients (1.5%), delayed gross hematuria in 5 patients (2.5%), respectively. Significant improvement in clinical outcomes were noted as early as 3 months after PVP treatment. CONCLUSIONS: PVP is considered as a high satisfaction rate by patient and a minimal postoperative complication. Hence, PVP is a novel, safe, effective and minimal invasive treatment for patients with symptomatic BPH.

Aged↗

Determination of protein-DNA binding constants and specificities from statistical analyses of single molecules: MutS-DNA interactions.

Atomic force microscopy (AFM) is a powerful technique for examining the conformations of protein-DNA complexes and determining the stoichiometries and affinities of protein-protein complexes. We extend the capabilities of AFM to the determination of protein-DNA binding constants and specificities. The distribution of positions of the protein on the DNA fragments provides a direct measure of specificity and requires no knowledge of the absolute binding constants. The fractional occupancies of the protein at a given position in conjunction with the protein and DNA concentrations permit the determination of the absolute binding constants. We present the theoretical basis for this analysis and demonstrate its utility by characterizing the interaction of MutS with DNA fragments containing either no mismatch or a single mismatch. We show that MutS has significantly higher specificities for mismatches than was previously suggested from bulk studies and that the apparent low specificities are the result of high affinity binding to DNA ends. These results resolve the puzzle of the apparent low binding specificity of MutS with the expected high repair specificities. In conclusion, from a single set of AFM experiments, it is possible to determine the binding affinity, specificity and stoichiometry, as well as the conformational properties of the protein-DNA complexes.

Adenosine Triphosphatases↗

Dissolution dynamics of NaCl nanocrystal in liquid water.

The dissolution dynamics of a NaCl nanocrystal in liquid water was studied using molecular dynamics simulations. The dissolution process was found to start with a Cl(-) ion at a corner site, followed by a Na(+) ion nearby. Both show directional preference in the dissolution path. An ion sequence with alternating charge, i.e., Cl(-), Na(+), Cl(-), Na(+), etc. was found to dominate the dissolution process. This image can be understood from the ionic hydration structures and the Coulomb interaction between the ions.

Journal Article↗

The derivation of two additional human embryonic stem cell lines from day 3 embryos with low morphological scores.

BACKGROUND: Immune rejection can lead to the failure of human embryonic stem cell (hES cell) transplantation. One approach to address the problem is to establish hES cell line banks. Due to the limited source of human embryos and to ethical reasons, the hES cell lines are not readily available. This study was undertaken to determine whether discarded day 3 embryos with low morphological scores could develop into blastocysts and produce hES cell lines. METHODS: A total of 130 day 3 embryos with low morphological scores were cultured to blastocyst stage, and inner cell masses (ICM) were isolated by immunosurgery. Colonies derived from the ICM were passaged every 4-7 days and evaluated for cell surface markers, differentiation potentials and karyotypes. RESULTS: A total of 19 blastocysts were obtained from 130 embryos (quality score <16), which resulted in the formation of 10 ICM, and two cell lines. Both cell lines satisfied the criteria that characterize pluripotent hES cells. CONCLUSION: Our results suggest that a subset with poor quality day 3 embryos judged on the basis of morphological assessment can form blastocysts and give rise to hES cell lines.

Blastocyst↗

Activation of mitochondrial ATP-sensitive potassium channels improves rotenone-related motor and neurochemical alterations in rats.

Our previous studies revealed that activation of mitochondrial ATP-sensitive potassium channels exerted protective effects on rotenone-treated rats and cultured cells. The aim of the present study is to examine the potential therapeutic effects of iptakalim, an ATP-sensitive potassium-channel opener, and diazoxide, a selective mitochondrial ATP-sensitive potassium-channel opener, on Parkinsonian symptoms in rats induced by rotenone. Rats were treated with rotenone (2.5 mg/kg s.c.) daily for 4 wk. This treatment caused a depletion of dopamine in the striatum and substantia nigra. Behaviourally, rotenone-infused rats exhibit Parkinsonian symptoms. Catalepsy was estimated by a 9-cm bar test. Treatment with L-dopa (10 mg/kg.d p.o.), iptakalim (0.75, 1.5, 3.0 mg/kg.d p.o.) and diazoxide (3.0 mg/kg.d p.o.) for 2 wk improved behavioural dysfunction and elevated dopamine contents in the striatum and substantia nigra of rotenone-treated rats. Studies also found that iptakalim and diazoxide could reduce the enzymic activities and mRNA levels of inducible nitric oxide synthase elicited by chronic administration of rotenone. All neurorestorative effects by both iptakalim and diazoxide were abolished by 5-hydroxydecanoate, a selective mitochondrial ATP-sensitive potassium-channel blocker. Collectively, the data suggested that mitochondrial ATP-sensitive potassium channels play a key role in improving both Parkinsonian symptoms and neurochemistry alterations of rotenone model rats, and selective activation of mitochondrial ATP-sensitive potassium channels may provide a new therapeutic strategy for treatment of early Parkinson's disease.

Animals↗

[125I seed implantation in sphincter preservation for treatment of low rectal cancer].

OBJECTIVE: To evaluate the effects of (125)I seed implantation in sphincter preservation for treatment of low rectal cancer. METHODS: Seventy-six patients with low rectal cancer were randomly divided into 2 group: group A, 17 males and 13 females, aged 48.5 +/- 2.4, receiving rectostomy and anal sphincter preservation and group B, 24 males and 22 females, aged 49.4 +/- 2.6, receiving modified TME and anal sphincter preservation combined with brachytherapy by (125)I seed implantation. Two to four weeks after operation chemotherapy with 5-FU/CF were performed. Follow-up was carried out 6, 12, 24, and 36 months after operation. RESULTS: The local recurrence rates 6, 12, 24, and 36 months after operation were 0%, 11.1%, 14.3%, and 23% respectively in the group A, and all 0% in the group B (P < 0.05 for the rate 36 months later). The survival rates 6, 12, 24, and 36 months after operation were 100%, 100%, 85.7%, and 76.7% respectively in the group A, and were 100%, 100%, 97.1%, and 93% respectively in the group B (P < 0.05 for the rate 36 months later). The functions of defecation and erection were better in the group B and the symptom of pain was improved better in the group A too (all P < 0.05). CONCLUSIONS: Safe, simple, and effective, surgery with sphincter preservation combined with brachytherapy in low rectal cancer is one of the ideal methods for treatment of low rectal cancer.

Adenocarcinoma↗

Involvement of CD147 in overexpression of MMP-2 and MMP-9 and enhancement of invasive potential of PMA-differentiated THP-1.

BACKGROUND: During infection and inflammation, circulating blood monocytes migrate from the intravascular compartments to the extravascular compartments, where they mature into tissue macrophages. The maturation process prepares the cells to actively participate in the inflammatory and immune responses, and many factors have been reported to be involved in the process. We found in our study that CD147 played a very important role in this process. RESULTS: By using PMA-differentiated human monocyte cells line THP-1, we found that CD147 mediated matrix metalloproteinases (MMPs) expression of the leukemic THP-1 cells and thus enhanced the invasiveness of THP-1 cells. After 24 hours of PMA-induced monocyte differentiation, the mean fluorescence intensity of CD147 in differentiated THP-1 cells (289.61 +/- 31.63) was higher than that of the undifferentiated THP-1 cells (205.1 +/- 19.25). There was a significant increase of the levels of proMMP-2, proMMP-9 and their activated forms in the differentiated THP-1 cells. Invasion assays using reconstituted basement membrane showed a good correlation between the invasiveness of THP-1 cells and the production of MMP-2 and MMP-9. The difference in the MMPs expression and the invasive ability was significantly blocked by HAb18G/CD147 antagonistic peptide AP-9. The inhibitory rate of the secretion of proMMP-9 in the undifferentiated THP-1 cells was 45.07%. The inhibitory rate of the secretion of proMMP-9, the activated MMP-9 and proMMP-2 in the differentiated THP-1 cells was 52.90%, 53.79% and 47.80%, respectively. The inhibitory rate of invasive potential in the undifferentiated cells and the differentiated THP-1 cells was 41.82 % and 25.15%, respectively. CONCLUSION: The results suggest that the expression of CD147 is upregulated during the differentiation of monocyte THP-1 cells to macrophage cells, and CD147 induces the secretion and activation of MMP-2 and MMP-9 and enhances the invasive ability of THP-1 cells. The matured monocytes / macrophages, via their high expression of CD147, may play an important role in promoting the tissue repair or tissue damage during their inflammatory response.

Basigin↗

Systematic administration of iptakalim, an ATP-sensitive potassium channel opener, prevents rotenone-induced motor and neurochemical alterations in rats.

Our previous studies revealed that iptakalim, a novel ATP-sensitive potassium channel opener, has a significant neuroprotective function against ischemia in vivo or rotenone-induced neurotoxicity in vitro. To investigate the potential pharmaceutical benefit of ATP-sensitive potassium channel openers on neurodegenerative diseases, we studied the effects of iptakalim and diazoxide, a selective mitochondrial ATP-sensitive potassium channel opener, on the rotenone-induced nigrostriatal degeneration in rats. Iptakalim (1.5 mg/kg/day, orally) or diazoxide (1.5 mg/kg/day, orally) alone was administered to rats for 3 days, and then for 4 weeks was used daily with an injection of rotenone (2.5 mg/kg/day, subcutaneously) 1 hr later each time. The results showed that rotenone-infused rats exhibited parkinsonian symptoms and had dopamine depletion in the striatum and substantia nigra. Pretreatment with iptakalim or diazoxide prevented rotenone-induced catalepsy and the reduction of striatum dopamine contents. Moreover, iptakalim and diazoxide reduced the enzymatic activities and mRNA levels of inducible nitric oxide synthase elicited by chronic administration of rotenone. These neuroprotective effects of iptakalim and diazoxide were abolished by 5-hydroxydecanoate, a selective mitochondrial ATP-sensitive potassium channel blocker. In conclusion, our data suggested that mitochondrial ATP-sensitive potassium channels might play a key role in preventing both parkinsonian symptoms and neurochemistry alterations induced by rotenone in rats. The selective activation of mitochondrial ATP-sensitive potassium channels may provide a new therapeutic strategy for prevention and treatment of neurodegenerative disorders such as Parkinson's disease.

ATP-Binding Cassette Transporters↗

[Latest cognition of treatment on deep vein thrombosis of lower extremity].

OBJECTIVE: To explore the effects of surgical procedure combined with the intravascular minimal invasive technique for the treatment of deep vein thrombosis (DVT) of lower extremity. METHODS: At the curse of disease from six hours to ninety days, one hundred and two patients with DVT including one hundred and three lower extremities had received surgical procedure and intravascular minimal invasive treatment. RESULTS: There were not procedure-related morbidities in 102 cases, and symptoms disappeared, all procedures were successful based on angiography. The detecting head for the intravascular ultrasound ablation was entered to inferior vena cava (IVC) in 74 cases (78%), Forgarty catheter was entered to IVC in 21 cases (21%), the stenosis in the confluence of the common iliac vein and IVC was dilated by sacculus rotundus catheter in 89 cases (88%), including 9 patients underwent percutaneous transluminal stenting. One hundred and two patients followed up for twenty months, follow-up by angiography showed no restenosis in 91 cases, restenosis in ilio-femoral vein in 1 cases, and thrombus recontouring in 4 cases, as well as 6 cases died caused by primary disease. CONCLUSION: Surgical procedure combined with the intravascular minimal invasive technique is a safe and effective therapeutic method for DVT.

Adult↗

Enhancement of third-order optical nonlinearities in 3-dimensional films of dielectric shell capped Au composite nanoparticles.

The composite nanoparticles of Au-core capped by CdS shells of different thickness were prepared and assembled into densely packed 3-dimensional films by the layer-by-layer self-assembly (LBL) technique. These films exhibited the 3-dimensional structure of densely packed Au@CdS composite nanoparticles and the shell thickness was tunable by changing the concentration of Cd2+-thiourea complexes. These multilayer films exhibited enhanced third-order optical nonlinear responses and ultrafast response times (several picoseconds). The third-order nonlinear optical susceptibility of the film with the CdS shell thickness of 4.4 nm was estimated to be 1.48 x 10(-9) esu and the value decreases with the increase of the CdS shell thickness. The enhancement of the optical nonlinearity was explained based on the calculation according to the electrostatic approximation by the solution of Laplace's equation under the boundary conditions appropriate to the model of core-shell nanoparticles, and mainly attributed to localized electric field effects in the CdS shell region. Additionally, the nonlinearity was optimized by determination of the values of the dielectric constant and thickness of the different shell.

Journal Article↗

[Clinical study of CT virtual endoscopy in staging diagnosis of bladder tumors].

OBJECTIVE: To evaluate CT virtual endoscopy (CTVE) based on spiral CT in the staging diagnosis of bladder neoplasms and its clinical application. METHODS: Forty patients with bladder neoplasms and 10 normal patients underwent volume scanning using spiral CT. All images with thin collimation and overlapping reconstruction were transferred to computer workstation to obtain the images of CTVE. The results of all CTVE findings were compared with those of conventional CT, cystoscopy, operation and pathological data. RESULTS: CTVE showed the normal anatomical structure of bladder as actual cystoscopy. The size, configuration, location and extension of bladder neoplasms was detected by CTVE scans agreed with that of actual cystoscopy. CTVE revealed the structure of trigone of urinary bladder that were not available in actual cystoscopy, and they were confirmed operatively and compared with the pathological results according to the TNM classification of malignant neoplasms. The sensitivity of CTVE for bladder tumors and accuracy in preoperative neoplasms staging was 98% (39/40) and 85% (33/39), respectively. The sensitivity of mass detection of diameter > or = 0.5 cm was 100%. The results were studied in a blind way. CONCLUSIONS: CTVE is a noninvasive, safe and reliable procedure in the staging diagnosis of bladder neoplasms. CTVE can well show bladder neck anatomy and serve as an important complementary method to conventional cystoscopy. The limitation of CTVE is that it can not observe change of mucosal appearances and perform biopsy.

Adolescent↗

Measurement of ionizing radiation using carbon nanotube field effect transistor.

Single-walled carbon nanotubes (SWNTs) are a new class of highly promising nanomaterials for future nano-electronics. Here, we present an initial investigation of the feasibility of using SWNT field effect transistors (SWNT-FETs) formed on silicon-oxide substrates and suspended FETs for radiation dosimetry applications. Electrical measurements and atomic force microscopy (AFM) revealed the intactness of SWNT-FET devices after exposure to over 1 Gy of 6 MV therapeutic x-rays. The sensitivity of SWNT-FET devices to x-ray irradiation is elucidated by real-time dose monitoring experiments and accumulated dose reading based on threshold voltage shift. SWNT-FET devices exhibit sensitivities to x-rays that are at least comparable to or orders of magnitude higher than commercial MOSFET (metal-oxide semiconductor field effect transistor) dosimeters and could find applications as miniature dosimeters for microbeam profiling and implantation.

Electrons↗

Function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome coronavirus.

To identify the function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome (SARS) coronavirus (CoV), we analyzed the protein-protein interaction among HAb18G/CD147, cyclophilin A (CyPA), and SARS-CoV structural proteins by coimmunoprecipitation and surface plasmon resonance analysis. Although none of the SARS-CoV proteins was found to be directly bound to HAb18G/CD147, the nucleocapsid (N) protein of SARS-CoV was bound to CyPA, which interacted with HAb18G/CD147. Further research showed that HAb18G/CD147, a transmembrane molecule, was highly expressed on 293 cells and that CyPA was integrated with SARS-CoV. HAb18G/CD147-antagonistic peptide (AP)-9, an AP of HAb18G/CD147, had a high rate of binding to 293 cells and an inhibitory effect on SARS-CoV. These results show that HAb18G/CD147, mediated by CyPA bound to SARS-CoV N protein, plays a functional role in facilitating invasion of host cells by SARS-CoV. Our findings provide some evidence for the cytologic mechanism of invasion by SARS-CoV and provide a molecular basis for screening anti-SARS drugs.

Antigens, CD↗

Fabrication of well-defined PLGA scaffolds using novel microembossing and carbon dioxide bonding.

A novel biologically benign technique was developed to produce three-dimensional tissue engineering scaffolds with well-defined structure. Photolithography was used to design and pattern a planar scaffold skeletal structure on a photoresist (SU-8), and a variety of microembossing processes including sacrificial layer embossing and bilayer embossing were developed to transfer the skeletal pattern to the poly(DL-lactide-co-glycolide) substrate as scaffold skeletons. Subcritical carbon dioxide was then introduced to assemble these skeletons to a three-dimensional scaffold at a low temperature. Compared with conventional scaffolds, which have a broad pore size distribution and varying pore geometry, these microfabricated scaffolds have a uniform and well-defined geometry and structure. This uniformity of structural parameters allows for the studies of cell attachment, spreading, and proliferation in scaffolds in a controlled and logical manner. The cytocompatibility of these microfabricated scaffolds was tested by seeding three different cell lines with different morphologies and growth patterns into these scaffolds. All three cell lines attached well to the scaffolds and grew to high densities as observed with scanning electron microscopy. This study demonstrates a controllable method to fabricate tissue scaffolds with a well-defined 3D architecture that can be used to better elucidate the effect of structure parameters such as pore geometry and pore size on tissue growth in 3D scaffolds.

Animals↗

Studies of ATP-sensitive potassium channels on 6-hydroxydopamine and haloperidol rat models of Parkinson's disease: implications for treating Parkinson's disease?

In the present study, we first investigated the effects of unilateral 6-hydroxydopamine (6-OHDA) lesioning of the substantia nigra pars compacta (SNc) on the expression of subunits of ATP-sensitive potassium channels (KATP channels) in the prefrontal cortex (PFC), striatum and hippocampus of adult rats by utilizing semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry techniques. The results show that Kir6.2 and SUR2 expression in the PFC, Kir6.1, Kir6.2 and SUR1 expression in the striatum, and Kir6.1 and Kir6.2 expression in the hippocampus of injured side increased significantly after unilateral 6-OHDA lesioning of the SNc in rats. Afterward, we studied the effects of iptakalim (Ipt), a novel ATP-sensitive potassium channel opener (KCO), on parkinsonian symptoms, which were induced by acute injection of haloperidol. The results indicate that intraperitoneal injection of Ipt (0.125 mg/kg, 0.25 mg/kg or 0.5 mg/kg) partially alleviated haloperidol-induced catalepsy and hypolocomotion. Even though the observed effects (0.5 mg/kg) are better than those of l-3,4-dihydroxyphenylalanine (L-DOPA) (100 mg/kg), Ipt (0.25 mg/kg) failed to enhance the anti-parkinsonian actions of L-DOPA (100 mg/kg). Our results suggest that KATP channels might be involved in the pathogenesis of Parkinson's disease (PD) induced in an animal model and conceptually support the idea that KATP channels may be new therapeutic targets for PD.

Adenosine Triphosphate↗