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Biomedical subjects

Tao Guo

Publications and source records attributed to Tao Guo.

At least 37 records · Page 2Linked to original sources

Development of BACE1 inhibitors for Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. The production and accumulation of beta-amyloid peptides (Abeta) from the beta-amyloid precursor protein (APP) are believed to play a key role in the onset and progression of AD. BACE1 (beta-site APP cleaving enzyme 1) is the protease responsible for the N-terminal cleavage of APP leading to the production of Abeta peptides and the development of BACE1 inhibitors as potential therapeutic agents for AD has generated tremendous interests from both academia and the pharmaceutical industry. A wide variety of BACE1 inhibitors have been reported, several of which have demonstrated highly promising efficacy in animal models of AD. This review focuses on recent disclosures of BACE1 inhibitors in the patent and scientific literature, covering the period from approximately May 2004 to November 2005.

Alzheimer Disease↗

[Study on absorption spectra of malignant plasma of esophagus].

There are too many articles about diagnosing cancers by the content of tumor chemical signs in plasma, but there are few articles about diagnosing them by spectroscopy. The present article belongs to the few. The authors can differentiate the normal and malignant esophagus by the statistic and analysis of absorption spectra after their plasmas are detected by spectrophotometry, which provide a new approach to quickly diagnosing malignant esophagus.

Biomarkers, Tumor↗

[Studies on preparation of sustained-release Shuxiong formulation, a traditional Chinese medicine compound recipe, using time-controlled release techniques].

OBJECTIVE: To prepare a sustained-release formulation of traditional Chinese medicine compound recipe by adopting time-controlled release techniques. METHOD: Shuxiong tablets were chosen as model drug. The prescription and technique of core tablets were formulated with selecting disintegrating time and swelling volume of core tablets in water as index. The time-controlled release tablets were prepared by adopting press-coated techniques, using PEG6000, HCO and EVA as coating materials. The influences of compositions, preparation process and dissolution conditions in vitro on the lag time (T(lag)) of drug release were investigated. RESULT: The composition of core tablets was as follow: 30% of drug, 50% MCC and 20% CMS-Na. The T(lag) of time-controlled release tablets was altered remarkably by PEG6000 content of the outer layer, the amount of outer layer and hardness of tablet. The viscosity of dissolution media and basket rotation had less influence on the T(lag) but more on rate of drug release. CONCLUSION: The core tablets pressed with the optimized composition had preferable swelling and disintegrating properties. The shuxiong sustained-release formulations which contained core tablet and two kinds of time-controlled release tablets with 3 h and 6 h of T(lag) could release drug successively at 0 h, 3 h and 6 h in vitro. The technique made it possible that various components with extremely different physicochemical properties in these preparations could release synchronously.

Carthamus tinctorius↗

Discovery and SAR of 4-amino-2-biarylbutylurea MCH 1 receptor antagonists through solid-phase parallel synthesis.

-4-Amino-2-arylbutylbenzamides such as 1 were identified as micromolar MCH 1 receptor (MCH1R) antagonists via screening using a scintillation proximity assay based on [125I]-MCH binding to recombinant, human MCH1R. Subsequent lead optimization efforts using solid-phase parallel synthesis resulted in the defined structure-activity relationships and the identification of 4-amino-2-biarylbutylureas, such as 11g, as potent single digit nanomolar MCH1R antagonists.

Combinatorial Chemistry Techniques↗

Calcium signaling in cardiac ventricular myocytes.

Calcium (Ca) is a multifunctional regulator of diverse cellular functions. In cardiac muscle Ca is a direct central mediator of electrical activation, ion channel gating, and excitation-contraction (E-C) coupling that all occur on the millisecond time scale. The key amplification step in E-C coupling is under tight control of very local [Ca]. Ca also directly activates signaling via kinases and phosphatases (e.g., Ca-calmodulin-dependent protein kinase [CaMKII] and calcineurin) that occur over a longer time scale (seconds to minutes), and the co-localization of these Ca-dependent modulators to their targets and to Ca is also critical in distinct signaling pathways. Finally, Ca-dependent signaling is also involved in long-term (minutes to hours/days) alterations in gene expression (or excitation-transcription coupling). These pathways are involved in hypertrophy and heart failure, and they can alter the expression of some of the key Ca regulatory proteins involved in E-C coupling and their regulation by kinases and phosphatases. There may again be physical microenvironments involved in this nuclear transcription, such that they sense a discrete Ca signal that is distinct from that involved in E-C coupling. In this way cells can use Ca signaling in multiple ways that function in spatially and temporally distinct manners.

Animals↗

[Combined cardiac resynchronization and implantable cardioversion defibrillation].

OBJECTIVE: To examine the efficacy and safety of implantation of the device with combined cardiac resynchronization therapy (CRT) and implantable cardioversion defibrillation (ICD) capabilities. METHODS: Eleven patients aged 48 - 80 (71.6 +/- 9.5) years, 7 male and 4 female, were included in the study. All patients had either a history of aborted sudden cardiac death, ventricular tachyarrhythmia, or induced ventricular tachycardia during cardiac electrophysiological study, whose left ventricular ejection fractions were 35% or less and QRS durations were 120 or longer. The patients were implanted a Medtronic INSYNC II MARQUIS(TH) 7289. All left ventricular leads were implanted in left lateral or left posterior lateral side-branches of coronary sinus. The procedures were performed in general anesthesia status. The AV interval was optimized guided by ECHO in all the patients in the day after the procedure. RESULTS: All procedures were successfully completed without major complications. The fluoroscopy time was 19 - 73 (44.7 +/- 19.9) min. Atrial lead amplitude, resistance and threshold were 0.5 - 3.5 (2.47 +/- 0.77) mV, 410 - 749 (590 +/- 126) Omega and 0.9 - 3.0 (1.37 +/- 0.71) V respectively. Right ventricular septal lead amplitude, resistance and threshold were 6.8 - 15.8 (11.00 +/- 3.48) mV, 387 - 750 (586 +/- 116) Omega and 0.4 - 1.0 (0.69 +/- 0.21) V respectively. The amplitude, resistance and threshold of left ventricular leads were 1.2 - 25 (15.37 +/- 5.15) mV, 423 - 812 (602 +/- 125) Omega and 0.3 - 5.0 (1.62 +/- 1.59) V respectively. The defibrillation thresholds (DFT) of 20 J were obtained in 3 patients, 6 J in 3 patients, and 15 J, 12 J and 3 J in one patient respectively. One of the 11 patients with failed old device did not obtain successful DFT after lead and device replacement and was defibrillated externally during DFT test. The another one did not obtain successful DFT because of abnormal ST-T changes in ECG. All devices were programmed to maximum of 30 J and discharged from the hospital in 48 hours except the one who failed to obtain DFT. The patients with mitral regurgitation improved after the AV optimization. CONCLUSIONS: Implantation of device with CRT and ICD features is safe even in aging patients. The long time outcomes of the clinical efficacy of this combined device remain to be observed.

Aged↗

Molecular analysis of the CRINKLY4 gene family in Arabidopsis thaliana.

The maize (Zea mays L.) CRINKLY4 (CR4) gene encodes a serine/threonine receptor-like kinase that controls an array of developmental processes in the plant and endosperm. The Arabidopsis thaliana (L.) Heynh. genome encodes an ortholog of CR4, ACR4, and four CRINKLY4-RELATED (CRR) proteins: AtCRR1, AtCRR2, AtCRR3 and AtCRK1. The available genome sequence of rice (Oryza sativa L.) encodes a CR4 ortholog, OsCR4, and four CRR proteins: OsCRR1, OsCRR2, OsCRR3 and OsCRR4, not necessarily orthologous to the Arabidopsis CRRs. A phylogenetic study showed that AtCRR1 and AtCRR2 form a clade closest to the CR4 group while all the other CRRs form a separate cluster. The five Arabidopsis genes are differentially expressed in various tissues. A construct formed by fusion of the ACR4 promoter and the GUS reporter, ACR4::GUS, is expressed primarily in developing tissues of the shoot. The ACR4 cytoplasmic domain functions in vitro as a serine/threonine kinase, while the AtCRR1 and AtCRR2 kinases are not active. The ability of ACR4 to phosphorylate AtCRR2 suggests that they might function in the same signal transduction pathway. T-DNA insertions were obtained in ACR4, AtCRR1, AtCRR2, AtCRR3 and AtCRK1. Mutations in acr4 show a phenotype restricted to the integuments and seed coat, suggesting that Arabidopsis might contain a redundant function that is lacking in maize. The lack of obvious mutant phenotypes in the crr mutants indicates they are not required for the hypothetical redundant function.

Amino Acid Sequence↗

Nitric oxide regulation of myocardial O2 consumption and HEP metabolism.

NO and O(2) compete at cytochrome-c oxidase, thus potentially allowing NO to modulate mitochondrial respiration. We previously observed a decrease of myocardial phosphocreatine (PCr)/ATP during very high cardiac work states, corresponding to an increase in cytosolic free ADP. This study tested the hypothesis that NO inhibition of respiration contributes to this increase of ADP. Infusion of dobutamine + dopamine (DbDp, each 20 microg.kg(-1).min(-1) iv) to more than double myocardial oxygen consumption (MVo(2)) in open-chest dogs caused a decrease of myocardial PCr/ATP measured with (31)P NMR from 2.04 +/- 0.09 to 1.85 +/- 0.08 (P < 0.05). Inhibition of NO synthesis with N(omega)-nitro-L-arginine (L-NNA), while catecholamine infusion continued, caused PCr/ATP to increase to the control value. In a second group of animals, L-NNA administered before catecholamine stimulation (reverse intervention of the first group) increased PCr/ATP during basal conditions. In these animals L-NNA did not prevent a decrease of PCr/ATP at the high cardiac work state but, relative to MVo(2), PCr/ATP was significantly higher after L-NNA. In a third group of animals, pharmacological coronary vasodilation with carbochromen was used to prevent changes in coronary flow that might alter endothelial NO production. In these animals L-NNA again restored depressed myocardial PCr/ATP during catecholamine infusion. The finding that inhibition of NO production increased PCr/ATP suggests that during very high work states NO inhibition of mitochondrial respiration requires ADP to increase to drive oxidative phosphorylation.

Adenosine Diphosphate↗

Small molecule biaryl FSH receptor agonists. Part 1: Lead discovery via encoded combinatorial synthesis.

High-throughput screening of two million compounds in 37 distinct encoded combinatorial libraries using FSH receptor transfected cells provided small molecule agonists such as 1 (EC(50)=3 microM) and 2 (EC(50)=3.9 microM), based on which a focused combinatorial library with a total of 31372 compounds was designed, synthesized, and screened to reveal 72 novel biaryl FSH receptor agonists such as 8a-c as well as a unique combinatorial SAR.

Combinatorial Chemistry Techniques↗

DBSubLoc: database of protein subcellular localization.

We have built a protein subcellular localization annotation database, the DBSubLoc database, which is available at http://www.bioinfo.tsinghua. edu.cn/dbsubloc.html. Annotations were taken from primary protein databases, model organism genome projects and literature texts, and then were analyzed to dig out the subcellular localization features of the proteins. The proteins are also classified into different categories. Based on sequence alignment, non-redundant subsets of the database have been built, which may provide useful information for subcellular localization prediction. The database now contains >60,000 protein sequences including approximately 30,000 protein sequences in the non-redundant data sets. Online download, search and Blast tools are also available.

Animals↗

Autologous stem cell transplantation for myocardial repair.

Current therapies for heart failure due to transmural left ventricular (LV) infarction are limited. We have developed a novel patch method for delivering autologous bone marrow stem cells to sites of myocardial infarction for the purpose of improving LV function and preventing LV aneurysm formation. The patch consisted of a fibrin matrix seeded with autologous porcine mesenchymal stem cells labeled with lacZ. We applied this patch to a swine model of postinfarction LV remodeling. Myocardial infarction was produced by using a 60-min occlusion of the left anterior descending coronary artery distal to the first diagonal branch followed by reperfusion. Results were compared between eight pigs with stem cell patch transplantation, six pigs with the patch but no stem cells (P), and six pigs with left anterior descending coronary artery ligation alone (L). Magnetic resonance imaging data collected 19 +/- 1 days after the myocardial infarction indicated a significant increase of LV systolic wall thickening fraction in the infarct zone of transplanted hearts compared with P or L hearts. Blue X-gal staining was observed in the infarcted area of transplanted hearts. PCR amplification of specimens from the X-gal-positive area revealed the Ad5 RSV-lacZ vector fragment DNA sequence. Light microscopy demonstrated that transplanted cells had differentiated into cells with myocyte-like characteristics and a robust increase of neovascularization as evidenced by von Willebrand factor-positive angioblasts and capillaries in transplanted hearts. Thus this patch-based autologous stem cell procedure may serve as a therapeutic modality for myocardial repair.

Animals↗

Perfusion homogeneity of hepatic parenchyma in magnetic resonance imaging during splenoportography.

OBJECTIVE: To evaluate the homogeneity of hepatic parenchyma enhancement in magnetic resonance imaging during splenoportography (MRSP) in the portal phase. METHODS: MRSP was performed in 16 patients suspected of space-occupying lesions in the livers. The signal intensity of non-lesion abnormal perfusion areas and that of peripheral parenchyma were measured in all the scanning phases including unenhanced phase, portographic phase, equilibrium phase, and delayed phase. RESULTS: Perfusion abnormalities were observed in 8 non-lesion foci in the portal phase in 4 cases of hepatic cirrhosis, most frequently appearing in triangle or fan-like shapes (7/8) with unpredictable locations. Hepatic cirrhosis patients had more non-lesion perfusion abnormalities than non-cirrhosis patients. CONCLUSIONS: The presence of non-lesion perfusion abnormalities in MRSP does not affect the diagnosis of the disease, and more homogeneous enhancement of the hepatic parenchyma in the portal phase can be achieved in MRSP than in CT during arterial portography and magnetic resonance imaging during arterial portography.

Adult↗

[Improved laparoscopic Vechitti procedure for constructing a functioning vagina].

OBJECTIVE: To investigate the clinical effect of improved laparoscopic Vechitti procedure for constructing a functioning vagina. METHODS: By using the method of raising vestibular mucosa, 18 patients with congenital absence of vagina and uterus underwent surgery in our hospital. No cave was made between bladder and rectum. The procedure involved puncturing the vulvar vestibulum pit with an epidural paracentetic needle or specially-made needle into abdominal cavity through rectovesical interspace, two drag-lines was introduced through anterior abdominal wall, using the line to tie a clothes button of 2.0-2.5 cm diameter to the vulva, rasing the lines day by day, the vestibule go upward along with the button, then the vagina was formed. RESULTS: After the procedures, the artificial vagina of all 18 patients could hold a speculum and the mucosa appeared soft and smooth with normal lubrication. The vulvar tissues appeared uninjured and normal in all cases. The married patients were satisfactory to the intercourse. One case of vagino-rectal fistula was observed in a patient after she rode a bicycle with the vaginal mould. CONCLUSION: The improved laparoscopic Vechitti procedure for constructing a functioning vagina has less trauma than conventional operation and is easy to operate. Therefore, the new improved procedure is a preferred way in constructing vagina for treating those patients.

Adult↗

[The process study on the extraction of irone by supercritical fuilds extraction].

OBJECTIVE: To study the condition for the extraction of irone in Iris tectorum by supercritical fluids extraction. METHOD: Conditions for the extraction were studied by a systematic method as guided by the content of irone presented in the extract. RESULTS: The best SFE conditions were: 0.411 mm raw material powder of Iris tectorum, 3% CHCl3 as modifier, temperature of extraction 50 degrees C under the pressure of 25 MPa, with CO2 flow rate of 120L/h, the static extracting time 2 h.

Carbon Dioxide↗

Fingerprint analysis of Flos Carthami by capillary electrophoresis.

Capillary electrophoresis (CE) was employed in fingerprint analysis of Flos Carthami. A standardized procedure was used to develop the CE fingerprint. An electrophoretic profile of genuine Flos Carthami from Fengqiu, He'nan, China, was first established as the characteristic fingerprint. This profile was then used to identify and assess the consistency of the herb. A study with a limited number of samples from nine sources showed a fair consistency in their CE fingerprints with that of the genuine sample. Flos Carthami was well distinguished from Stigma Croci, a possible substitute in traditional Chinese medicine, and Flos Hemerocallis, a commercial adulterant, by comparing the fingerprints of each herb.

Asteraceae↗