Biomedical subjects

Bo Liu

Publications and source records attributed to Bo Liu.

At least 55 records · Page 3Linked to original sources

PubMed2006

Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity.

The c-Jun N-terminal kinases (JNK-1, -2, and -3) are members of the mitogen activated protein (MAP) kinase family of enzymes. They are activated in response to certain cytokines, as well as by cellular stresses including chemotoxins, peroxides, and irradiation. They have been implicated in the pathology of a variety of different diseases with an inflammatory component including asthma, stroke, Alzheimer's disease, and type 2 diabetes mellitus. In this work, high-throughput screening identified a JNK inhibitor with an excellent kinase selectivity profile. Using X-ray crystallography and biochemical screening to guide our lead optimization, we prepared compounds with inhibitory potencies in the low-double-digit nanomolar range, activity in whole cells, and pharmacokinetics suitable for in vivo use. The new compounds were over 1,000-fold selective for JNK-1 and -2 over other MAP kinases including ERK2, p38alpha, and p38delta and showed little inhibitory activity against a panel of 74 kinases.

Aminopyridines↗

PubMed2006

Microbial metabolism of methyl protodioscin by Aspergillus niger culture--a new androstenedione producing way from steroid.

Methyl protodioscin (1), a natural furostanol biglycoside steroid, was a preclinical anticancer drug, which showed potent activity against most cell lines from leukemia and solid tumors in the National Cancer Institute's (NCI) human cancer panel. Metabolism of methyl protodioscin by Aspergillus niger was investigated. Seven metabolites were isolated and identified. Two main metabolites were pregnane glycosides and four were furostanol glycosides, together with the aglycone. It was found that steroidal saponin skeleton could be converted to pregnenolone skeleton only using microbial methods, which must have chemical procedures in the reported literatures. The proposed biosynthetic pathways of the microbial conversion products of methyl protodioscin were drawn. The found enriched the reaction types of microbial bioconversion and provided a new producing way of androstenedione from steroid. Most metabolites showed strong cytotoxic activities against HepG2, NCI-H460, HeLa, and MCF-7 cell lines.

Adenocarcinoma↗

PubMed2006

Synthesis and photophysical processes of 9-bromo-10-naphthalen-2-yl-anthracene.

A novel luminescent compound, 9-bromo-10-naphthalen-2-yl-anthracene (BNA) is synthesized by Suzuki Cross-coupling reaction of 9-bromo-anthracene and naphthalene-2-boronic acid. The structure is characterized by (1)H NMR, IR and UV-vis spectroscopy. The photophysical processes of 9-bromo-10-naphthalen-2-yl-anthracene have been carefully investigated by UV-vis absorption and fluorescence spectra. The results show that the compound emits blue and blue-violet light. The emission spectra exhibit obvious solvent effect. With the difference in polarity of solvents, The emission spectra is not only slightly blue shift with the increase of the solvent polarity but also change on the intensity of fluorescence at room temperature . The light emitting can be quenched by electron donor, N,N-dimethylaniline (DMA). On adding gradually DMA into the solution of BNA, the emission intensities of fluorescence are gradually decreased. The quenching effect follows the Stern-Volmer equation.

Acetates↗

PubMed2006

2,4-diaminopyrimidine derivatives as potent growth hormone secretagogue receptor antagonists.

Ghrelin, a gut-derived orexigenic hormone, is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R). Centrally administered ghrelin has been shown to cause hunger and increase food intake in rodents. Inhibition of ghrelin actions with ghrelin antibody, peptidyl GHS-R antagonists, and antisense oligonucleosides resulted in weight loss and food intake decrease in rodents. Here we report the effects of GHS-R antagonists, some of which were potent, selective, and orally bioavailable. A structure-activity relationship study led to the discovery of 8a, which was effective in decreasing food intake and body weight in several acute rat studies.

Animals↗

PubMed2006

Isolation of mutations that bypass the requirement of the septation initiation network for septum formation and conidiation in Aspergillus nidulans.

The kinase cascade of the septation initiation network (SIN), first revealed in fission yeast, activates the contraction of the actomyosin ring, and plays an essential role in fungal septation. Mob1p, an evolutionarily conserved SIN protein, is associated with the most downstream kinase of this cascade in fission yeast. In this study, the mobA gene encoding a homologous protein was isolated from the filamentous fungus Aspergillus nidulans, whose mycelium is made of multinucleate cells. The MOBA protein was required for septation and conidiation, but was not essential for hyphal extension and colony formation. To identify genes that act antagonistically against the SIN, UV mutagenesis was carried out to isolate suppressor (smo) mutations that restored conidiation when MOBA was not expressed. Microscopic examination indicated that the restored conidiation was concomitant with restored septation in the absence of the MOBA protein. Eight recessive smo mutations in five complementation groups also bypassed the requirement of the SIN kinases SEPH and SIDB for septum formation and conidiation. However, none of these smo mutations affected the localization of MOBA. Among smo mutations, smoA and smoB mutations caused reduced hyphal growth and colony formation. They also rendered hypersensitivity to low doses of the microtubule-depolymerizing agent benomyl for conidiation. Therefore, in A. nidulans, proteins encoded by the smo genes likely have an antagonistic interaction against the SIN pathway to regulate septation and conidiation.

Actomyosin↗

PubMed2006

Differences in electronic properties of fluorinated and trifluoromethylated fullerenes revealed by their propensity for dianion formation.

The cross sections for electron transfer from sodium to C(60)F(n) (-) and C(60)(CF(3))(n) (-) anions in 50-keV collisions as a function of the number of functional groups n are reported. There are clear differences between derivatives of fluorine and trifluoromethyl due to the different electron withdrawing properties of F and CF(3). The role of inductive effects and pi electron delocalization on the electron affinity is discussed, assuming a correlation between the cross section and the electron affinity of the anion.

Journal Article↗

PubMed2006

[Effects of different treatment complex on esophageal vascular structures in patients with portal hypertension].

OBJECTIVE: To assess the effects of different treatment complex on esophageal vascular structures in patients with portal hypertension. METHODS: Patients (142 cases) with esophageal varices received either endoscopic variceal ligation (EVL) alone (54 cases), pericardial devascularization procedure (PDP) alone (23 cases), a combination of EVL and partial splenic embolization (PSE) (34 cases), or a combination of EVL and PDP (31 cases) for variceal eradication. Esophageal vascular structures were examined with miniature ultrasonic probe. The recurrence and rebleeding of esophageal varices were investigated. RESULTS: Esophageal submucous varices were obliterated and collateral veins remained unchanged in patients treated by EVL or EVL combined with PSE; esophageal submucous varices were diminished in size and collateral veins were obliterated by PDP, and both esophageal submucous varices and collateral veins were obliterated by the combination of EVL and PDP. CONCLUSIONS: The combination of EVL and Hassab's procedure can effectively shut off the portoazygous shunt, prevent esophageal varices from bleeding and recurrence. It's a simply and less cost procedure.

Cardia↗

PubMed2006

Building up key segments of N-glycans in the gas phase: intrinsic structural preferences of the alpha(1,3) and alpha(1,6) dimannosides.

The intrinsic conformer specific vibrational spectra of two important subunits of the core pentasaccharide of N-linked glycans, the alpha(1,3) and alpha(1,6) dimannosides, have been recorded in the gas phase. Coupling these measurements with a computational exploration of their conformational landscapes has enabled their conformational assignment and has identified characteristic vibrational signatures associated with particular conformational families-including those that do or do not display inter-ring hydrogen bonding across the glycosidic linkage. In addition, the IR spectra of the monosaccharide moieties provide benchmarks, through which the conformational assignments can be refined. This introduces a general concept of modularity and secondary structure in oligosaccharides--essential for the success of similar studies on larger oligosaccharides in the future.

Carbohydrate Conformation↗

PubMed2006

PKCdelta is necessary for Smad3 expression and transforming growth factor beta-induced fibronectin synthesis in vascular smooth muscle cells.

OBJECTIVE: The purpose of these studies is to investigate the mechanism by which transforming growth factor (TGF)beta1 regulates the synthesis of the extracellular matrix protein fibronectin (FN). METHODS AND RESULTS: TGFbeta1 elicited a time-dependent induction of FN protein and mRNA in A10 rat aortic smooth muscle cells (SMCs). Ectopic expression of Smad3 in A10 cells stimulated both basal and TGFbeta1-induced FN expression, whereas expression of Smad7 eliminated the TGFbeta response. Because TGFbeta activated PKCdelta in SMCs, we tested the role of PKCdelta in regulation of FN expression. Inhibition of PKCdelta activity by rottlerin or dominant-negative adenovirus (AdPKCdelta DN) blocked TGFbeta1's induction of FN, whereas overexpression of PKCdelta enhanced TGFbeta's effect. Moreover, aortic SMCs isolated from PKCdelta(-/-) mice exhibited diminished FN induction in response to TGFbeta. Furthermore, we found that Smad3 protein and mRNA were markedly reduced in AdPKCdelta DN-treated A10 cells and in PKCdelta null cells. Finally, restoring Smad3 in rottlerin-treated A10 and PKCdelta null cells rescues the ability of TGFbeta to upregulate FN protein and mRNA expression. CONCLUSIONS: Our data suggest that TGFbeta-activated PKCdelta is critical to maintain normal expression of Smad3, which in turn is required for the induction of fibronectin. PKCdelta represents a promising target for treating the fibroproliferative response after arterial injury.

Adenoviridae↗

PubMed2006

Optimization of 2,4-diaminopyrimidines as GHS-R antagonists: side chain exploration.

The synthesis and structure-activity relationships of the 4- and 6-substituents of 2,4-diaminopyrimidine-based growth hormone secretagogue receptor (GHS-R) antagonists are described. Diaminopyrimidines with 6-norbornenyl (4n) and 6-tetrahydrofuranyl (4p) substitutents were found to exhibit potent GHS-R antagonism and good selectivity (approximately 1000-fold) against dihydrofolate reductase.

Pyrimidines↗

PubMed2006

Total synthesis of phorboxazole B.

An efficient and highly convergent total synthesis of the potent antitumor agent phorboxazole B has been achieved. The synthetic strategy of this synthesis features: 1) a highly efficient substrate-controlled hydrogenation to construct the functionalized cis-tetrahydropyrane unit; 2) iterative crotyl addition to synthesize the segment that contains alternating hydroxyl and methyl substituents; 3) Hg(OAc)2/I2-induced cyclization to establish the cis-tetrahydropyrane moiety; 4) 1,3-asymmetric induction in the Mukaiyama aldol reaction to afford the stereogenic centers at C9 and C3; and 5) the exploration of the Still-Gennari olefination reaction to complete the macrolide ring of phorboxazoloe B.

Antineoplastic Agents↗

PubMed2006

A novel approach for estimating growth phases and parameters of bacterial population in batch culture.

Using mathematical analysis, a new method has been developed for studying the growth kinetics of bacterial populations in batch culture. First, sampling data were smoothed with the spline interpolation method. Second, the instantaneous rates were derived by numerical differential techniques and finally, the derived data were fitted with the Gaussian function to obtain growth parameters. We named this the Spline-Numerical-Gaussian or SNG method. This method yielded more accurate estimates of the growth rates of bacterial populations and new parameters. It was possible to divide the growth curve into four different but continuous phases based on changes in the instantaneous rates. The four phases are the accelerating growth phase, the constant growth phase, the decelerating growth phase and the declining phase. Total DNA content was measured by flow cytometry and varied depending on the growth phase. The SNG system provides a very powerful tool for describing the kinetics of bacterial population growth. The SNG method avoids the unrealistic assumptions generally used in the traditional growth equations.

Algorithms↗

PubMed2006

Effect of genetic variations of the POU1F1 gene on growth traits of Nanyang cattle.

PCR-RFLP was applied to analyze the effect of the genetic variations of the POU1F1 gene on growth traits of 100 Nanyang cattle. The results showed that the 451 bp PCR product digested with Hinf I demonstrated polymorphism in the population, which was at Hardy-Weinberg equilibrium. Moreover, the frequencies of alleles A/B in the Nanyang population were 0.465/0.535. The association of the variations of the POU1F1 gene with the growth traits in the population was analyzed. The following parameters were greater in individuals with a genotype BB than in those with an genotype AB: birth weight, average weight increase before ablactation, body height at 12 months, body weight, body length, and chest girth at 6 months and 12 months (P<0.05). The body weight at 12 months was higher in the BB individuals than in the AA individuals (P <0.05). The body weight and body sizes also showed a trend of allele B> allele A in the other age groups. Therefore, the genotype BB maybe a dominant genotype and the allele B may be a dominant allele. These results imply that the allele B of the POU1F1 gene is likely to positively affect the growth traits.

Alleles↗

PubMed2006

Effects of tetrandrine on cytosolic free calcium concentration in corpus cavernosum smooth muscle cells of rabbits.

AIM: To study the relaxation mechanisms of tetrandrine (Tet) on the corpus cavernosum smooth muscle. METHODS: The corpus cavernosum smooth muscle cells from New Zealand white rabbits were cultured in vitro. [Ca(2+)](i) was measured by Fluorescence Ion Digital Imaging System, using Fluo-2/AM as a Ca(2+)-sensitive fluorescent indicator. RESULTS: Tet (1, 10 and 100 micromol/L) had no effect on the resting [Ca(2+)](i) (P>0.05). In the presence of extracellular Ca(2+) (2.5 mmol/L), Tet (1, 10 and 100 micromol/L) inhibited [Ca(2+)](i) elevation induced by high K(+) and phenylephrine (PE) in a concentration-dependent manner (P>0.05). In calcium free solution containing egtaic acid, Tet (1 and 10 micromol/L) had no inhibitory effects on [Ca(2+)](i) elevation induced by PE (P>0.05). However, Tet (100 micromol/L) inhibited [Ca(2+)](i) elevation induced by PE (P>0.05). CONCLUSION: Tet inhibited the Ca(2+) influx from the extracellular site via voltage-activated Ca(2+) channel and alpha(2)-adrenoceptor-operated Ca(2+) channel. At a high concentration, Tet might inhibit the cytosolic calcium pool release in cultured corpus cavernosum smooth muscle cells. This inhibitory action on [Ca(2+)](i) might be one of the relaxation mechanisms of Tet on the corpus cavernosum smooth muscle.

Alkaloids↗

PubMed2006

[Analysis of POU1F1 gene polymorphisms in Qinchuan cattle and Chinese Holstein cattle].

PCR-RFLP was applied to analyze the polymorphisms of POU1F1 gene in 218 Qinchuan cattle (QQ) and Chinese Holstein cattle (HC). Results demonstrated Hinf I polymorphisms in the 451 bp PCR product in the two populations. The frequencies of alleles A/B in QQ and HC populations were 0.232/0.768 and 0.132/0.868, respectively. The frequencies of three genotypes AA, AB and BB were 0.030/0.403/0.567 and 0.007/0.251/0.742, respectively. Qinchuan cattle population was at Hardy-Weinberg equilibrium at this locus, but Chinese Holstein cattle population was not. The gene heterozygosity/effective allele gene number/Shannon information entropy/polymorphism information content of Qinchuan cattle and Chinese Holstein cattle populations were listed for 0.356/1.553/0.541/0.292 and 0.229/1.297/0.390/0.203, respectively. All indices were higher in the Qinchuan cattle population.

Animals↗

PubMed2006

[Design and control of in vitro pulse modulated microwave exposure system].

This paper presents the design and development of a set of microwave exposure system based on 1.8GHz mobile RF signal. This system can work on several modulation types to do microwave exposure experiment under different specific absorption rate (SAR) and prepare the way for researches in the effect exerted by the electromagnetic signal of mobile on human health. The hardware is made up of several RF instruments, waveguide and computer, and the software introduces the accomplishment of the control system and the algorithm of control.

Algorithms↗

PubMed2006

[Experimental study on effect of tiangui gengnian soft capsule on aged female rats with osteoporosis].

OBJECTIVE: To investigate the effect of Tiangui Gengnian soft capsule (TGC), which mainly consists of seabuckthorn fatty acid, on serum estrogen and estrogen receptor (ER) in multiple target tissues as uterus, liver and bone, in aged female rats, in order to explore its mechanism from the aspects of receptor and cytokines. METHODS: Low (0.72 g/kg), middle (1.80 g/kg) and high (4.50 g/kg) dose of TGC were administered by gastrogavage to young and aged (22 months old) female rats with osteoporosis for 45 days, and diethylstilbestrol (0.02 mg/kg) was used as a positive control. The levels of serum estradiol (E2), transforming growth factor beta1 (TGF-beta1), insulin-like growth factor-1 (IGF-1) were measured by radioimmunoassay and ELISA method, the protein expression of their receptor in bone, uterus and liver was detected by SABC immunohistochemistry, and the mRNA expression of E2 in uterus and liver detected by in situ hybridization with digoxin probe. RESULTS: Intervention of TGC could cause increase of serum E2, IGF-1 and TGF-beta1 levels, the TGF-beta1 reached 90.63 +/- 18.71 pg/L in the group administered with high dose, which was significantly different to that in the aged group (P < 0.01). There was no obvious effect of the mRNA expression of E2 in uterus and liver, and no effect of TGF-beta1 and IGF-1 in liver in rats. CONCLUSION: TGC could improve the postmenopausal bone metabolism, alleviate and correct the bone loss, it is possibly realized by way of side-secreting/auto-secreting of E2 receptor and cytokines (TGF-beta1 and IGF-1) to improve the osteogenesis and inhibit the destruction of bone.

Animals↗

PubMed2006

[Effects of senility on inducible nitric oxide synthase expression and cell apoptosis in rat penis].

OBJECTIVES: To investigate the effect of senility on inducible nitric oxide synthase (iNOS) expression and apoptosis in rat penis. METHODS: The rats were divided into three groups randomly: senescent, aged and young. Their penises were harvested to detect iNOS expression by immunohistochemistry and cell apoptosis rate by TUNEL, respectively. RESULTS: iNOS expression were 0.24 +/- 0.03, 0.17 +/- 0.02, 0.12 +/- 0.03 (relative A) and cell apoptosis rate were (1.41 +/- 0.78)%, (0.94 +/- 0.43)% and (0.50 +/- 0.23 )%, respectively, in the tissues of three groups. The differences among three groups were considerable significance (P <0.05). CONCLUSION: It maybe one of the mechanisms of erectile dysfunction in the aging male that senility causes the increase of iNOS expression and cell apoptosis.

Aging↗