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Biomedical subjects

H Yuan

Publications and source records attributed to H Yuan.

At least 19 recordsLinked to original sources
PubMed2006

Mitochondrial fission is an upstream and required event for bax foci formation in response to nitric oxide in cortical neurons.

Mitochondrial dysfunction is an underpinning event in many neurodegenerative disorders. Less clear, however, is how mitochondria become injured during neuronal demise. Nitric oxide (NO) evokes rapid mitochondrial fission in cortical neurons. Interestingly, proapoptotic Bax relocates from the cytoplasm into large foci on mitochondrial scission sites in response to nitrosative stress. Antiapoptotic Bcl-xL does not prevent mitochondrial fission despite its ability to block Bax puncta formation on mitochondria and to mitigate neuronal cell death. Mitofusin 1 (Mfn1) or dominant-negative dynamin-related protein 1(K38A) (Drp1(k38A)) inhibits mitochondrial fission and Bax accumulation on mitochondria induced by exposure to an NO donor. Although NO is known to cause a bioenergetic crisis, lowering ATP by glycolytic or mitochondrial inhibitors neither induces mitochondrial fission nor Bax foci formation on mitochondria. Taken together, these data indicate that the mitochondrial fission machinery acts upstream of the Bcl-2 family of proteins in neurons challenged with nitrosative stress.

Adenosine Triphosphate↗
PubMed2006

Intracellular ATP-sensitive K+ channels in mouse pancreatic beta cells: against a role in organelle cation homeostasis.

AIMS/HYPOTHESIS: ATP-sensitive K(+) (K(ATP)) channels located on the beta cell plasma membrane play a critical role in regulating insulin secretion and are targets for the sulfonylurea class of antihyperglycaemic drugs. Recent reports suggest that these channels may also reside on insulin-containing dense-core vesicles and mitochondria. The aim of this study was to explore these possibilities and to test the hypothesis that vesicle-resident channels play a role in the control of organellar Ca(2+) concentration or pH. METHODS: To quantify the subcellular distribution of the pore-forming subunit Kir6.2 and the sulfonylurea binding subunit SUR1 in isolated mouse islets and clonal pancreatic MIN6 beta cells, we used four complementary techniques: immunoelectron microscopy, density gradient fractionation, vesicle immunopurification and fluorescence-activated vesicle isolation. Intravesicular and mitochondrial concentrations of free Ca(2+) were measured in intact or digitonin-permeabilised MIN6 cells using recombinant, targeted aequorins, and intravesicular pH was measured with the recombinant fluorescent probe pHluorin. RESULTS: SUR1 and Kir6.2 immunoreactivity were concentrated on dense-core vesicles and on vesicles plus the endoplasmic reticulum/Golgi network, respectively, in both islets and MIN6 cells. Reactivity to neither subunit was detected on mitochondria. Glibenclamide, tolbutamide and diazoxide all failed to affect Ca(2+) uptake into mitochondria, and K(ATP) channel regulators had no significant effect on intravesicular free Ca(2+) concentrations or vesicular pH. CONCLUSIONS/INTERPRETATION: A significant proportion of Kir6.2 and SUR1 subunits reside on insulin-secretory vesicles and the distal secretory pathway in mouse beta cells but do not influence intravesicular ion homeostasis. We propose that dense-core vesicles may serve instead as sorting stations for the delivery of channels to the plasma membrane.

ATP-Binding Cassette Transporters↗
PubMed2006

A comparison of bone formation in biphasic calcium phosphate (BCP) and hydroxyapatite (HA) implanted in muscle and bone of dogs at different time periods.

Physicochemical modification could implement synthetic materials into osteoinductive materials, which induce bone formation in nonosseous tissues. We hereby studied the relevance between the osteogenic capacities of osteoinductive materials in nonosseous tissues and in osseous sites. Biphasic calcium phosphate ceramic (BCP) and hydroxyapatite ceramic (HA) were implanted in femoral muscles and femoral cortical bone of dogs for 7, 14, 21, 30, 45, 60, 90, 180, and 360 days, respectively. Two dogs were used in each time point. In each dog, four cylinders (phi5x6 mm) per material were implanted in femoral muscles and 2 cylinders (phi5x6 mm) per material in femoral cortical bone. The harvested samples were processed for both histological and histomorphometric analyses. Bone was observed in BCP implanted in femoral muscles since day 30, while in HA since day 45. Quantitatively, more bone was formed in BCP than in HA at each time point after day 30 (p<0.05). The earlier and more bone formed in BCP than in HA suggests BCP a higher osteoinductive potential than HA in muscle. In femoral cortical bone defects, a bridge of bone in the defect with BCP was observed at day 21, while with HA at day 30. At days 14, 21, and 30, significantly more bone was formed in BCP than in HA (p<0.05). The results herein show that osteogenic capacities of osteoinductive materials in nonosseous tissues and osseous sites are correlated: the higher the osteoinductive potential of the material, the faster the bone repair.

Animals↗
PubMed2006

AUNX1, a novel locus responsible for X linked recessive auditory and peripheral neuropathy, maps to Xq23-27.3.

BACKGROUND: We report here the genetic characterisation of a large five generation Chinese family with the phenotypic features of auditory neuropathy and progressive peripheral sensory neuropathy, and the genetic feature of X linked recessive inheritance. Disease onset was at adolescence (at an average age of 13 years for six affected subjects). The degree of hearing impairment varied from mild to severe, with decreased otoacoustic emissions; auditory brainstem responses were lacking from onset. METHODS: Two-point and multipoint model based linkage analysis using the MILNK and LINKMAP programs of the FASTLINK software package produced maximum two-point and multipoint LOD scores of 2.41 and 2.41, respectively. RESULTS: These findings define a novel X linked auditory neuropathy locus/region (AUNX1, Xq23-q27.3). This region is 42.09 cM long and contains a 28.07 Mb region with flanking markers DXS1220 and DXS8084, according to the Rutgers Combined Linkage-Physical Map, build 35. However, mutation screen of the candidate gene SLC6A14 within the region did not identify the causative genetic determinant for this large Chinese family.

China↗
PubMed2006

Novel self-aggregates of chitosan oligosaccharide grafted stearic acid: preparation, characterization and protein association.

A novel hydrophobically modified chitosan oligosaccharide (CSO) containing 5.4 stearic acid (SA) groups per 100 anhydroglucose units was synthesized by an 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The purified copolymer was structurally characterized by IR spectroscopy. Characteristics of self-aggregates of the amphiphilic copolymers were studied by fluorescence spectroscopy and dynamic light scattering. The critical aggregation concentration (cac) value of the self-aggregates in aqueous solution was determined by measuring the fluorescence intensity of pyrene as a fluorescent probe. Mean diameter of self-aggregates in pH 7.0 PBS was 25.0 +/- 14.7 nm with a unimodal size distribution. The diameter, as well as the zeta potential of self-aggregates increased when the pH value of dispersion medium decreased. Bovine serum albumin (BSA) was further enveloped in the interface of different single self-aggregate and formed nanoparticles. The size of BSA-loaded stearic acid modified CSO nanoparticles depended on the pH values of the dispersed aqueous vehicle, and the size diminished when the pH values of the dispersed aqueous vehicle decreased, whilst, the BSA encapsulation efficiency enhanced. The nanoparticles were characterized by Transmission Electron Microscopy (TEM). BSA release from stearic acid modified CSO nanoparticles decreased when the pH values of the delivery media decreased, in the range from 7.2 to 5.8.

Chitosan↗
PubMed2006

Effect of PEG2000 on drug delivery characterization from solid lipid nanoparticles.

The purpose of this work is to develop a PEG2000-modified solid lipid nanoparticles (SLN) intended to encapsulate a drug within their matrix and to study their characteristics. In the present report, drug-loaded SLN were prepared by a novel solvent diffusion method in an aqueous system. Monostearin and PEG2000 were used as carrier material and modifying agent, respectively. The model drug salbutamol sulphate was incorporated to study the characterization of entrapment efficiency, size, zeta potential (charge) and drug delivery characterization. In the test solution of pH 7.2 phosphate buffer, drug-release behavior from SLN suspension exhibited a biphasic pattern. With the monoastearin-based SLN, a distinctly prolonged release over a monitored period of 14 days was observed after a burst drug release in the first 8 hours. Over the monitored period of prolonged release, there was delayed release in the first 5 days with nearly 2.51% of the drug released each day, following which a slightly higher release rate (8.14% per day) appeared in the last 9 days. In contrast, the drug release rate from PEG2000-modified SLN was faster. Nevertheless, further work is required in order to optimize the release behavior of various entrapped drugs. These results also demonstrate that modification with PEG2000 can accelerate release of hydrophilic small molecule drugs from SLN.

Albuterol↗
PubMed2005

Humanin delays apoptosis in K562 cells by downregulation of P38 MAP kinase.

Humanin (HN) is a newly identified neuroprotective peptide. In this study, we investigated its antiapoptotic effect and the potential mechanisms in K562 cells. Upon serum deprivation, expression of HN in K562 cells decreased and its intracellular distribution changed from cytoplasm to cell membrane. In HN stably transfected K562 cells, apoptosis was delayed compared with control vector transfected cells as measured by flow cytometry. Furthermore, analysis of different mitogen-activated protein (MAP) kinases activity revealed that extracellular signal-regulated kinase (ERK) pathway was inhibited while p38 signaling was activated following serum deprivation in K562 cells. And in HN transfected K562 cells, ERK downregulation was not affected, but p38 activation was suppressed, which may responsible for the delayed apoptosis in these cells. Activation of the ERK signaling pathway by phorbol myristate 13-acetate (PMA) and sorbitol protected K562 cells from serum deprivation induced apoptosis. Additionally, overexpression of HN reduced megakaryocytic differentiation of K562 cells. The present data outline the role of ERK and p38 MAP kinases in serum deprivation induced apoptosis in K562 cells and figure out p38 signaling pathway as molecular target for HN delaying apoptosis in K562 cells.

Apoptosis↗
PubMed2004

Preparation and characterization of solid lipid nanoparticles containing peptide.

Solid lipid nanoparticles (SLN) are an alternative colloidal carrier system for controlled drug delivery. However, only a few have been studied regarding the incorporation of peptides into SLN, due to the hydrophilic peptide not easy to enter the lipophilic matrix of SLN. In the present report, peptide-loaded solid lipid nanoparticles were prepared by a novel solvent diffusion method in an aqueous system. The model peptide gonadorelin was incorporated to study the entrapment efficiency, size, zeta potential (charge) and drug delivery characterization. Gonadorelin and monostearin were dissolved in acetone and ethanol at 50 degrees C in water bath, the resultant organic solution was poured into an aqueous containing 1% polyvinyl alcohol (PVA) under mechanical agitation. The peptide-loaded solid lipid nanoparticles were quickly produced and separated by centrifugation. The average volume diameter of gonadorelin-loaded SLN is 421.7 nm and the zeta potential of SLN is -21.1 mV dispersed in distilled water. Up to 69.4% of gonadorelin can be incorporated. In vitro release of gonadorelin from SLN is slow. In the test solution of a 0.1N hydrochloric acid for 2h and then transferred in a pH 6.8 phosphate buffer (simulative gastrointestinal fluid), the drug-release behavior from SLN suspension exhibited a biphasic pattern. After burst drug-release at the first 6h at a percentage of 24.4% of loaded gonadorelin, a distinctly prolonged release over a monitored period of 12 days was observed and nearly 3.81% of drug was released in each day. In the test solution of a pH 6.8 phosphate buffer (simulative intestinal fluid), the drug-release rate from SLN was similar to that in the simulative gastrointestinal fluid. Further, a novel preparation method in the present research for peptide-loaded SLN was established. These results also demonstrate the principle suitability of SLN as a prolonged release formulation for hydrophilic peptide drugs.

Delayed-Action Preparations↗
PubMed2004

A novel preparation of solid lipid nanoparticles with cyclosporin A for prolonged drug release.

Solid lipid nanoparticles were prepared by a novel solvent diffusion method in an aqueous system. The lipophilic model drug cyclosporin A was incorporated into SLN to study encapsulation efficiency, zeta potential (charge) and drug delivery. Stearylamine and cyclosporin A were dissolved in ethanol and acetone and the resultant organic solution was dropped into water at 60 degrees C. The drug-loaded SLN suspension quickly formed with an azury color. After burst drug release with 18% of the drug over the first 12 hours, a distinctly prolonged release over a monitored period of 16 days was observed, with nearly 4% of the drug being released each day. These results demonstrate the suitability of SLN produced with the proposed method as a prolonged release formulation for lipophilic drugs.

Amines↗
PubMed2003

Cloning of the KcURA3 gene and development of a transformation system for Kluyveromyces cicerisporus.

KcURA3 was cloned from Kluyveromyces cicerisporus CBS4857 by complementation of the ura3 mutation in Saccharomyces cerevisiae. KcURA3 encodes a 267-amino-acid protein with 80% sequence identity to that of S. cerevisiae. An ura3 mutant strain from K. cicerisporus CBS4857, named Y179U, was obtained by selection on 5-fluoroorotic acid plates. Sequence analysis of this mutated gene revealed that it contained a point mutation at nucleotide position +277. Two vectors, pUK1 and pUKD, bearing KcURA3 were constructed. Either the lithium acetate method or electroporation could be used to transform pUK1 and pUKD intoY179U. The transformation efficiency using electroporation was higher than that using the lithium acetate method.

Acetates↗
PubMed2002

Preparation of solid lipid nanoparticles with clobetasol propionate by a novel solvent diffusion method in aqueous system and physicochemical characterization.

Solid lipid nanoparticles (SLN) are a colloidal carrier system for controlled drug delivery. Monostearin SLN were prepared by a novel solvent diffusion method in an acidic aqueous system in order to improve the recovery of the method. The lipophilic model drug clobetasol propionate was incorporated to study the recovery of nanoparticles, entrapment efficacy, zeta potential (charge) and drug delivery characterization. The drug and monostearin were dissolved in acetone and ethanol at 50 degrees C in water bath, the resultant organic solution was poured into an acidic aqueous (pH 1.10) containing 1% polyvinyl alcohol (PVA) under mechanical agitation at room temperature. The drug loaded SLN was quickly produced with an aggregation state and easily separated by centrifugation. The recovery of nanoparticles was markedly increased compared to using a usual aqueous (pH 5.73) containing the same concentration of PVA. After burst drug release at the first 3 h, a distinctly prolonged release over a monitored period of 4 days was observed and nearly 6% drug was released in each day. Further, a novel preparation method and the optimized separation parameters in the present research for SLN were established. These results also demonstrate the principle suitability of SLN as a prolonged release formulation for lipophilic drugs.

Algorithms↗
PubMed2001

Application of solid-phase microextraction in the determination of diazepam binding to human serum albumin.

In this paper, protein-drug interactions were studied by solid-phase microextraction (SPME) using diazepam binding to human serum albumin as a model system. Since drug compounds are normally polar and nonvolatile by nature, direct SPME is used in this work. The SPME extraction is an equilibrium process among the concentrations of the analyte partitioned onto the SPME fiber, free and bound drug in the solution. A calibration curve was first constructed by employing the amount of the analytes partitioned on the fiber versus the free analyte concentration in the solution in the absence of protein. In method I, the extraction was performed in the protein solution with known diazepam concentration. In method II, diazepam was first loaded onto the fiber by extracting in solution with known diazepam concentration. This fiber was subsequently transferred into the protein solution for desorption. The amount of the analyte left on the fiber was analyzed after the system reached equilibrium. The free drug concentration was then obtained from the calibration curve for both methods. The Scatchard plot was finally employed to obtain the number of binding sites and the equilibrium binding constants. Since only a very small amount of the protein solution is required (150 microL for each extraction), method II is very useful for circumstances where the protein amount is very limited. The direct measurement method proposed in this paper does not need a GC response factor, which significantly decreases the experimental error. The only measurement needed is the area count change (ratio) of the fiber injections before and after the protein was introduced into the solution. The difference between the direct measurement method for method I and method II is discussed. The result illustrated that the SPME direct measurement method provided both theoretical accuracy and simplicity in such applications.

Calibration↗
PubMed2001

Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F.

We have determined the molecular basis for Usher syndrome type 1F (USH1F) in two families segregating for this type of syndromic deafness. By fluorescence in situ hybridization, we placed the human homolog of the mouse protocadherin Pcdh15 in the linkage interval defined by the USH1F locus. We determined the genomic structure of this novel protocadherin, and found a single-base deletion in exon 10 in one USH1F family and a nonsense mutation in exon 2 in the second. Consistent with the phenotypes observed in these families, we demonstrated expression of PCDH15 in the retina and cochlea by RT-PCR and immunohistochemistry. This report shows that protocadherins are essential for maintenance of normal retinal and cochlear function.

Adult↗
PubMed2001

Protective role of ATP-sensitive potassium channels in hypoxia-induced generalized seizure.

Adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels are activated by various metabolic stresses, including hypoxia. The substantia nigra pars reticulata (SNr), the area with the highest expression of K(ATP) channels in the brain, plays a pivotal role in the control of seizures. Mutant mice lacking the Kir6.2 subunit of K(ATP) channels [knockout (KO) mice] were susceptible to generalized seizures after brief hypoxia. In normal mice, SNr neuron activity was inactivated during hypoxia by the opening of the postsynaptic K(ATP) channels, whereas in KO mice, the activity of these neurons was enhanced. K(ATP) channels exert a depressant effect on SNr neuronal activity during hypoxia and may be involved in the nigral protection mechanism against generalized seizures.

Adenosine Triphosphate↗
PubMed2001

Bone induction by porous glass ceramic made from Bioglass (45S5).

Porous glass ceramic, which was prepared from Bioglass powder (45S5, U.S. Biomaterials) by foaming with diluted H(2)O(2) solution and sintering at 1000 degrees C for 2 h, was implanted as cylinders (5 mm in diameter and 6 mm in length) in thigh muscles of dogs for 3 months. Histological observation was made on thin un-decalcified sections. Bone formation was histologically found in pores of all implants (X16) retrieved from 16 dogs. The bone tissue was also identified with backscattered scanning electron microscopy observation (BSE) and energy dispersive X-ray microanalysis (EDX). This is the first report of bone induction in soft tissues of animals by glass ceramic that has long been recognized as a bioactive (osteoconductive) biomaterial. The present results justify the impetus to investigate the osteoinductivity of calcium phosphate-based biomaterials, to study the mechanism of bone induction (osteoinduction) by calcium phosphate-based biomaterials, to develop osteoinductive calcium phosphate-based biomaterials, and to examine the relation between osteoinduction and osteoconduction.

Animals↗
PubMed2001

[Study on endothelial dysfunction and platelet activation in elderly hypertensive patients complicated with cerebral infarction].

OBJECTIVE: The aim of this paper was to investigate endothelial dysfunction, platelet activation, and inflammation in elderly hypertensive patients and those complicated with cerebral infarction. METHODS: Twenty-eight elderly hypertensive patients complicated with cerebral infarction(within 72 hours after onset of neurological symptoms), thirty-one Stage I-II elderly hypertensive patients and twenty-eight elderly healthy individuals were selected as subjects. Their plasma concentrations of von Willebrand factor(vWF), alpha granule membrane protein-140(GMP-140), and serum concentrations of C-reaction protein(CRP) were examined. RESULTS: Elderly hypertensive patients complicated with cerebral infarction had significantly higher plasma vWF, GMP-140, and serum CRP than elderly hypertensive patients and elderly healthy individuals. Plasma vWF and GMP-140 were higher in elderly hypertensive patients than elderly healthy individuals, whereas serum CRP was increased slightly and there was no significant difference between elderly hypertensive patients and elderly healthy individuals. CONCLUSION: This study suggests that elderly hypertensive patients complicated with cerebral infarction have obvious endothelial dysfunction, platelet activation, and inflammatory change. Stage I-II elderly hypertensive patients have obvious endothelial dysfunction and platelet activation as well.

Aged↗