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Biomedical subjects

Yu Zhao

Publications and source records attributed to Yu Zhao.

At least 109 records · Page 6Linked to original sources

[Chemical constituents from Elsholtzia blanda].

OBJECTIVE: To investigate the constituents of Elsholtzia blanda. METHOD: The chemical components were isolated by polyamide and silica gel column chromatography. Their structures were identified with extensive spectral (EI-MS, ESI-MS, 1H-NMR, 13C-NMR, DEPT, 1H-1H-COSY, HMBC, HMQC) and chemical methods. RESULT: Five compounds were isolated and identified as luteolin (I), luteolin-5-O-beta-D-glucopyranoside (II), luteolin-7-O-beta-D-glucopyranoside (III), 5-hydroxy-7, 8 -dimethoxyflavone (IV) and 5-hydroxy-6, 7-dimethoxyflavone (V). CONCLUSION: Compounds III, IV, V were isolated from E. blanda for the first time and I was firstly separated from the genus Elsholtzia.

Flavonoids↗

[Effects of budesonide, desloratadine and dexamethasone on interleukine-4 release and expression from human mast cell line].

OBJECTIVE: Since human mast cell is an important source of cytokines, it is of importance to understand the effects of anti-allergic drugs on cytokines modulation in mast cells. In the present study, we aimed at observing whether IL-4 could be released from human mast cell line (HMC-1) after the stimulation of PMA + A23187, and the effects of systemic glucocorticosteroid, dexamethasone, topical glucocorticosteroid, budesonide and H1 antagonist, desloratadine on IL-4 release and mRNA expression. METHODS: HMC-1 was stimulated with 25 ng/ml phorbol 12-myristate 13-acetate (PMA) and 2.5 x 10(-7) mol/L ionomycin (A23187) and cultured for 6 hours, 12 hours and 24 hours respectively in the presence or absence of 10(-6)-10(-10) mol/L concentrations of test drugs. Culture supernatants were collected and the levels of IL-4 were assayed by enzyme-linked immunosorbent assays (ELISA). The mRNA expression of IL-4 was measured by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: HMC-1 expressed IL-4 mRNA and the resulting protein production of IL-4 released after being stimulated with PMA plus A23187. Dexamethasone, budesonide and desloratadine had potent inhibitory effect on IL-4 release at any concentrations and time points, with significant deference (P < 0.05) compared to the control cells. The inhibitory effect did not show time-dependent and concentration-dependent manner. Desloratadine and budesonide showed neither up-regulatory nor down-regulatory effects on IL-4 mRNA expression at the test concentrations, however, desloratadine could down-regulate IL-4 mRNA expression. CONCLUSIONS: HMC-1 could express and produce IL4 after stimulation. Dexamethasone, budesonide and desloratadine all had inhibitory effects on IL-4 release from HMC-1. In addition, desloratadine could also inhibit the IL-4 mRNA expression.

Budesonide↗

Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration.

Retina and retinal pigment epithelium (RPE) belong to the metabolically most active tissues in the human body. Efficient removal of acid load from retina and RPE is a critical function mediated by the choriocapillaris. However, the mechanism by which pH homeostasis is maintained is largely unknown. Here, we show that a functional complex of carbonic anhydrase 4 (CA4) and Na+/bicarbonate co-transporter 1 (NBC1) is specifically expressed in the choriocapillaris and that missense mutations in CA4 linked to autosomal dominant rod-cone dystrophy disrupt NBC1-mediated HCO3- transport. Our results identify a novel pathogenic pathway in which a defect in a functional complex involved in maintaining pH balances, but not expressed in retina or RPE, leads to photoreceptor degeneration. The importance of a functional CA4 for survival of photoreceptors implies that CA inhibitors, which are widely used as medications, particularly in the treatment of glaucoma, may have long-term adverse effects on vision.

Carbonic Anhydrase IV↗

Developmental expression of rat torsinA transcript and protein.

A GAG deletion in the gene (TOR1A) for torsinA is associated with childhood-onset generalized dystonia (DYT1). Environmental factors may contribute to development of the phenotype since mutations in TOR1A are clinically penetrant in less than 40% of cases. Median age of onset is 10 and appearance of dystonia after 28 is rare. As a step towards understanding the temporal window of DYT1 disease penetrance, we have examined torsinA transcript and protein expression in rats from the embryonic period through adulthood. With relative quantitative multiplex real-time RT-PCR, we detected torsinA transcript in both neural (cerebellar cortex, striatum, cerebral cortex, thalamus and hippocampus) and non-neural (liver, kidney and heart) tissues at each developmental time point tested (embryonic day 20 [E20], postnatal day 1 [P1], P7, P14, P36, 6 months, 1.5 years). Levels of torsinA transcript were highest at E20 or P1 in all tissues examined except for the cerebellum where transcript levels peaked at P14. Early postnatal levels of torsinA transcript were over three times higher than those seen in adult rats. With quantitative radioactive in situ hybridization, torsinA transcript was widely distributed in brain at all ages with levels peaking at P14 in both cerebellum and striatum. TorsinA-immunoreactivity (IR) was present in neurons throughout the brain. TorsinA-IR was detected in perikarya, dendrites and axons but not nuclei. At P14, prominent expression of torsinA was noted in both striatal cholinergic interneurons and cerebellar Purkinje cells. Our results suggest that torsinA may contribute to postnatal maturational events in the brain such as dendritic arborization and synaptogenesis. Furthermore, the time course of torsinA expression in discrete components of motor networks is compatible with the temporal window of clinical penetrance in DYT1 mutation carriers.

Animals↗

[Expression of calmodulin and nNOS in the paraspinal muscles in idiopathic scoliosis].

OBJECTIVE: The aim of this study was to identify whether one side of the apex of the scoliotic curve showed greater muscular abnormalities than the other. This investigation sought to compare directly the expression and localization of Calmodulin (CaM) and nNOS of the thoracic spinal musculature on convex side with those on the concave side in the scoliosis patients attending for spinal surgery. METHODS: The patient group comprised 8 females and 2 males, scheduled for spinal surgery, in whom the apex of the scoliotic curve arose between T6 and T11. Muscle biopsies were taken bilaterally during surgery from the superficial multifidus muscle at the apex of the curve between the 6th and 11th thoracic vertebral levels. Part of the tissue was fixed in Formalin and stained with hematoxylin and eosin; the remaining tissue was snap frozen and processed for immunohistochemistry and western blot. The following antibodies were used for the immunohistochemistry at dilutions optimized in preliminary experiments. Goat polyclonal anti-human-CaM and mouse monoclonal anti-human-nNOS were used as primary antibodies. CaM and nNOS were detected by immunohistochemical method and Western-blot. Western blotting was done with antibodies to CaM. RESULTS: Compared with control muscle and the muscle on the concave side of the scoliotic curve, A significant decrease in CaM and nNOS was found on the convex side of paraspinal muscle from idiopathic scoliosis patients, Western blotting with an CaM antibody and nNOS antibody shows that there are more CaM and nNOS protein in the concave side of paraspinal muscle in these patients with adolescent idiopathic scoliosis than in the convex side. CONCLUSION: This asymmetry of CaM and nNOS in the paraspinal muscle may play a role in the pathogenensis of IS.

Adolescent↗

Expression of several cytoskeletal proteins in ovine cerebral arteries: developmental and functional considerations.

Cytoskeleton proteins play important roles in regulating vascular smooth muscle (VSM) contraction and relaxation. We tested the hypotheses that the expression levels of several of these proteins change significantly during the course of development, and that these changes contribute to age-related changes in contractile responses. In cerebral arteries from 95-day (d) gestation and 140-d fetus, newborn lambs, and adult sheep, by Western immunoblot (n= 5 for each age) we quantified the relative expression of alpha-actin, alpha-tubulin, cyclophilin A, and proliferating cell nuclear antigen (PCNA). In addition, we examined middle cerebral artery tension responses to phenylephrine (PHE) stimulation in the absence or presence of cytochalasin D (3 x 10(-7)m) and nocodazole (3 x 10(-6)m), inhibitors of alpha-actin and alpha-tubulin polymerization, respectively. The expression levels of alpha-actin and cyclophilin A varied little during the course of development. In contrast, alpha-tubulin expression was approximately 2.5-fold greater in both fetal age groups as compared to adult. Also, as compared to adult and as expected, expression of PCNA was several-fold greater in cerebral arteries of the 95-d fetus (x8), 140-d fetus (x 5), and newborn (x 3). In both adult and fetal middle cerebral artery, cytochalasin D-induced inhibition of actin polymerization decreased PHE-induced contraction, to approximately 60 and approximately 40% of control, respectively (despite no significant change in expression level). In contrast, alpha-tubulin inhibition by nocodazole showed little effect on PHE-induced tension (in spite of the age-related decrease in expression). In conclusion, expression levels of alpha-actin, a thin filament protein involved in contraction, remained relatively constant during the course of development, as did the effects of inhibition of its polymerization on contractility. In contrast, alpha-tubulin, important in intracellular protein trafficking, showed a significant age-related decrease in expression and played a relatively minor role in contractility. The present studies suggest that other cytoskeletal structural proteins and/or elements of pharmaco-mechanical coupling are important to developmental differences in cerebrovascular contractility. In addition, the relatively constant expression levels of alpha-actin and cyclophilin A with development, suggest that these are useful internal standards for studies of cytosolic protein expression.

Actin Cytoskeleton↗

Study of thermal aggregation of oat globulin by laser light scattering.

The heat-induced aggregation of oat globulin was studied using size-exclusion chromatography (SEC) combined with on-line multiangle laser light scattering (MALLS) and quasi-elastic light scattering (QELS). The unheated oat globulin exists as a mixture of hexamer (>95%), trimer, and dimer forms of hexamer. The molecular weight of the hexamer was estimated by MALLS to be 330 000, close to that deduced from the genomic cloned data of the acidic and basic polypeptides of oat globulin. From QELS measurements, it can be predicted that the hexamer exists as two annular trimeric rings, with a diameter of 11.8 nm, placed on top of each other, forming an oblate cylinder with a height of about 8.5 nm. Upon heating at 100 degrees C, the oat globulin hexamers and trimers were dissociated into monomers. The heat-denatured monomers, probably assuming an extended structure, were associated to form small aggregates, which were further aggregated to high molecular weight complexes. Upon further heating (60 min), the soluble aggregates were associated to form insoluble aggregates. Aggregation of oat globulin occurred at a much faster rate at 110 degrees C. The results indicate that the SEC-MALLS-QELS system is suitable for studying thermal aggregation of food proteins.

Avena↗

Study of succinylated food proteins by Raman spectroscopy.

Three food protein products, soy protein isolates, spray-dried egg white, and whey protein isolates, were chemically modified to varying levels with succinic anhydride, and the extent of modification of these proteins were determined by standard wet chemistry methods. Raman spectra (500-2000 cm(-1)) of the modified proteins were obtained. New C=O stretching vibrations were observed at 1420 and 1737 cm(-1) and were attributed to the carboxylate (COO-) and ester carbonyl (RCOO-) groups, respectively, which were appended to the proteins during succinylation. Two series of calibration curves were obtained by plotting the intensity ratio of the 1420 and 1737 cm(-1) to 1003 cm(-1) phenylalanine stretching band (used as an internal standard) against the extent of substituted epsilon-amino (and alpha-amino) groups and aliphatic hydroxyl groups, respectively. Linear fits were obtained with correlation coefficient r > 0.988. The Raman spectral data were also analyzed to study the effect of succinylation on the conformation of the three proteins. Some conformational changes were observed, including a transition from ordered to disordered structures, an exposure of tryptophan residues from a buried, hydrophobic microenvironment, and probably conformational shift of cystine residues.

Dietary Proteins↗

Age-related macular degeneration: a high-resolution genome scan for susceptibility loci in a population enriched for late-stage disease.

Age-related macular degeneration (AMD) is a complex multifactorial disease that affects the central region of the retina. AMD is clinically heterogeneous, leading to geographic atrophy (GA) and/or choroidal neovascularization (CNV) at advanced stages. Considerable data exists in support of a genetic predisposition for AMD. Recent linkage studies have provided evidence in favor of several AMD susceptibility loci. We have performed a high-resolution (5-cM) genome scan of 412 affected relative pairs that were enriched for late-stage disease (GA and/or CNV). Nonparametric linkage analysis was performed using two different diagnostic criteria and also by dividing the affected individuals according to GA or CNV phenotype. Our results demonstrate evidence of linkage in regions that were suggested in at least one previous study at chromosomes 1q (236-240 cM in the Marshfield genetic map), 5p (40-50 cM), and 9q (111 cM). Multipoint analysis of affected relatives with CNV provided evidence of additional susceptibility loci on chromosomes 2p (10 cM) and 22q (25 cM). A recently identified Gln5345Arg change in HEMICENTIN-1 on chromosome 1q25 was not detected in 274 affected members in the restricted group with AMD, 346 additional patients with AMD, and 237 unaffected controls. Our results consolidate the chromosomal locations of several AMD susceptibility loci and, together with previous reports, should facilitate the search for disease-associated sequence variants.

Aging↗

Isomeric eremophilane lactones from Senecio tsoongianus.

From the whole plant of Senecio tsoongianus, two pairs of epimers, tsoongianolides A (1) and B (2), and tsoongianolides C (3) and D (4), and two new sesquiterpene lactones, tsoongianolides E (5) and F (6), all of which possess the eremophilane skeleton, were isolated. Two known eremophilane dimers (7) and (8) were also obtained from this species. Their absolute structures were elucidated by 1D- and 2D-NMR techniques and by X-ray diffraction studies, along with chemical evidence.

Isomerism↗

Dominant optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia: a syndrome caused by a missense mutation in OPA1.

PURPOSE: To describe the clinical features of and identify the disease-causing mutation in a large Utah family segregating a dominantly inherited syndrome of optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia. DESIGN: Observational case series. METHODS: Thirty individuals at risk for a syndrome of optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia in a single family underwent clinical examinations and venipuncture. Linkage analysis and mutation screening of the optic atrophy 1 gene (OPA1) were performed. RESULTS: Eighteen individuals demonstrated characteristics of the syndrome. Genetic analysis identified a G-->A substitution at nucleotide position 1334 in exon 14 of OPA1 causing an arginine-to-histidine change (R445H) in all affected members of the family. This change segregated with the disease phenotype in the study family with a LOD score of 7.02 at theta; = 0 and was not found in 200 normal control subjects. Analysis of an unrelated Belgian family with a similar phenotype revealed the same R445H mutation segregating with the disease phenotype. CONCLUSIONS: This study describes a mutation in OPA1 causing a unique syndrome of optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia. These results expand the spectrum of human disease associated with mutations of OPA1 and indicate that ophthalmologists caring for patients with optic atrophy should inquire about possible associated hearing loss. Although OPA1 is a nuclear gene, the gene product localizes to mitochondria, suggesting that mitochondrial dysfunction may be the final common pathway for many forms of syndromic and nonsyndromic optic atrophy, hearing loss, and external ophthalmoplegia.

Adolescent↗

Isolation and biological properties of polysaccharide CPS-1 from cultured Cordyceps militaris.

A polysaccharide from the water extract of cultured Cordyceps militaris was isolated through ethanol precipitation, deproteination and gel-filtration chromatography. Their molecular weight was determined using gel-filtration chromatography. The structure of polysaccharide CPS-1 was elucidated by sugar analysis, Smith degradation, IR and 13C-NMR spectroscopy. CPS-1 was shown to possess a significant antiinflammatory activity and suppressed the humoral immunity in mice but had no significant effects on the cellular immunity and the non-specific immunity.

Acetic Acid↗

Isolation, purification and identification of polysaccharides from cultured Cordyceps militaris.

Four polysaccharides from the water extract of cultured Cordyceps militaris were isolated through ethanol precipitation, deproteination and gel-filtration chromatography. Their molecular weights were determined using gel-filtration chromatography. Among the four isolated polysaccharides, the structures of two of them (CPS-2 and CPS-3) were elucidated by sugar analysis, Smith degradation, IR and (13)C-NMR spectroscopy.

Cordyceps↗

Three new oxetane-ring-containing taxoids from Taxus chinensis.

Three new 14beta-benzoyloxy taxoids containing an oxetane ring, namely, 14beta-benzoyloxybaccatin IV (1), 14beta-benzoyloxy-13-deacetylbaccatin IV (2), and 14beta-benzoyloxy-2-deacetylbaccatin VI (3), have been isolated from the leaves and stems of Taxus chinensis. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopic data.

Cyclization↗

Inhibition of the phosphodiesterase 4 (PDE4) enzyme reverses memory deficits produced by infusion of the MEK inhibitor U0126 into the CA1 subregion of the rat hippocampus.

Cyclic AMP-specific phosphodiesterase 4 (PDE4), which is an integral component of NMDA receptor-mediated cAMP signaling, is involved in the mediation of memory processes. Given that NMDA receptors also mediate MEK/mitogen-activated protein kinase (MAPK, ERK) signaling, which is involved in synaptic plasticity, and that some PDE4 subtypes are phosphorylated and regulated by ERK, it was of interest to determine if PDE4 is involved in MEK/ERK signaling-mediated memory. It was found that rolipram, a PDE4-selective inhibitor, reversed the amnesic effect in the radial-arm maze test of the MEK inhibitor U0126 administered into the CA1 subregion of the rat hippocampus. Consistent with this, rolipram, either by peripheral administration or direct intra-CA1 infusion, enhanced the retrieval of long-term memory impaired by intra-CA1 infusion of U0126 using the step-through inhibitory avoidance test. The same dose of rolipram did not affect U0126-induced reduction of phospho-ERK1/2 levels in the CA1 subregion. However, in primary cultures of rat cerebral cortical neurons, pretreatment with U0126 increased PDE4 activity; this was correlated with the U0126-induced reduction of phospho-ERK1/2 levels. These results suggest that MEK/ERK signaling plays an inhibitory role in regulating PDE4 activity in the brain; this may be a novel mechanism by which MEK/ERK signaling mediates memory. PDE4 is likely to be an important link between the cAMP/PKA and MEK/ERK signaling pathways in the mediation of memory.

3',5'-Cyclic-AMP Phosphodiesterases↗

Clinical and histologic evaluation of a new injectable implant: hydrophilic polyacrylamide gel.

Hydrophilic polyacrylamide gel is a new, jellylike transparent implant that consists of 95% water and 5% polyacrylamide, and it has been applied in many countries for many years as a sort of injectable implant. However, there are no data regarding human tissue reaction to hydrophilic polyacrylamide gel to date. Thirty-one patients who had undergone the injection of hydrophilic polyacrylamide gel for soft-tissue augmentation from September 1998 to November 2001 wanted to remove the implant. Hematoxylin-eosin-stained sections from each cyst of tissue sample were investigated and analyzed with light microscopy. The tissue slices of 12 patients who had received an injection of silicone from 1988 to 1994 were reviewed. The difference in histologic features was assessed. The inflammatory reaction of hydrophilic polyacrylamide gel was characterized by the presence of more foreign body giant cells. The cellular response ranged from moderate or marked (4 to 18 months) to mild (>18 months). The difference was statistically significant (P <0.05). Little lymphocyte infiltration was shown in all slices of hydrophilic polyacrylamide gel. There were clusters or diffuse lymphocyte infiltration on histologic observation of the liquid silicone. The difference was significant (P <0.001). In summary, hydrophilic polyacrylamide gel may evoke a human tissue inflammatory response similar to other foreign materials. Lumpy subcutaneous nodules, mastodynia, and difficult removal may limit its application in breast augmentation.

Acrylic Resins↗

[Effect of inhibitors for demethylation and histone deacetylase on proliferation of cell line K562 and expression of tumor related genes].

In order to observe the effect of inhibitors for demethylation and histone deacetylase on the growth of leukemia cell line K562 and the expressin of tumor related genes, the K562 cells were treated with 5-aza-2' deoxycytidine (DAC) and trichostatin A (TSA) in co-culture; the growth curves were observed; the cell cycle was detected by flow cytometry (FCM); the gene expression pattern before and after drug treatment was measured with Atlas7742-1 microarray. The results showed that the combination treatment of DAC and TSA inhibited the proliferation of K562 cells, the growth of most cells were stopped in G(1)/S phases after drug treatment, the gene expression after treatment was more than before, and a few gene expression were down-regulated. In conclusion, combination treatment of DAC and TSA had an inhibitive effect on the leukemia cell line K562, combination of DAC and TSA with microarray could be used for screening candidate genes inhibiting leukemia cells.

Azacitidine↗

[First-line Xeloda (Capecitabine) treatment for advanced and recurrent colorectal cancer].

OBJECTIVE: To evaluate the efficacy and safety of capecitabine as first-line therapy in patients with advanced and recurrent colorectal cancer. METHODS: From December 2000 to November 2001, sixty patients with advanced and recurrent colorectal cancer received first-line capecitabine treatment given at a dose of 1250 mg/m(2) twice daily, on days 1 - 14 every 21 days. At least 2 cycles were administered. RESULTS: The overall response rate was 23.3% with 14 PR, 24 SD (40.0%) and 15 PD. The median survival time was 14.7 months. The survival rate was 63.9% at 12-months and 33.4% at 24-months. Grade III-IV adverse effects were diarrhea in 4 patients (6.6%), anemia in 2 (3.3%) and hand-foot syndrome (HFS) in 1 (1.7%); Grade I-II adverse effects were hyperpigmentation in 20 (33.3%), HFS in 18 (30.0%) and diarrhea in 10 (16.7%). CONCLUSION: Capecitabine is an efficacious and better-tolerated alternative treatment for the patients with advanced and recurrent colorectal cancer.

Adult↗