Biomedical subjects

Zhiyong Zhang

Publications and source records attributed to Zhiyong Zhang.

At least 19 recordsLinked to original sources

PubMed2006

Entropic folding pathway of human epidermal growth factor explored by disulfide scrambling and amplified collective motion simulations.

Epidermal growth factor (EGF) regulates cell proliferation and differentiation by binding to the EGF receptor (EGFR) extra-cellular domains. Human EGF is a small, single-chain protein comprising three distinct loops (A, B, and C), which are connected by three disulfide bridges (Cys6-Cys20, Cys14-Cys31, and Cys33-Cys42). These disulfide bridges are essential for structural stability and biological activity. EGF was extensively studied by disulfide scrambling, an experimental technique for the conformational entrapment of intermediate states, which allows us to study the folding pathway of proteins containing disulfide bonds. The experimental results showed that there is a major 2-disulfide intermediate (denoted EGF-II) and that the native disulfide bonding pattern is less prevalent in one of the mutants. In this article, we investigated for the first time the solution conformations of wild-type EGF, EGF-II, and the mutant S9C through extensive molecular dynamics (MD) simulations in water using both the standard MD technique and a recently developed amplified-collective-motion (ACM) sampling method. Compared to standard MD simulations, we achieved a much more enhanced sampling by the ACM simulations, and the structures were sufficiently relaxed to estimate configurational entropies. The simulation results suggest a predominantly entropic folding pathway governed by the disorder of three functional loop regions. Although EGF-II exhibits two native disulfide bonds (Cys14-Cys31 and Cys33- Cys42), its large configurational entropy inhibits a direct transition to the native structure in the folding process. When Ser9 is mutated into Cys, a non-native disulfide bridge Cys9- Cys20 is slightly more favorable than the native Cys6-Cys20 because a less constrained N-terminus affords larger entropy. Isomers that are functionally less active also exhibit a more localized dynamics of the functional loop regions, which may suggest a possible mechanism for the modulation of EGF activity.

Amino Acid Sequence↗

PubMed2006

Neurotrophic receptor TrkB: Is it a predictor of poor prognosis for carcinoma patients?

The neurotrophic receptor tyrosine kinase TrkB, while binding its high affinity ligand brain-derived neurotrophic factor (BDNF), will play an essential role for nervous system development, neuronal survival, differentiation, and maintenance. However, accumulating evidences implies that TrkB signal pathway may also be involved in a variety of human cancers, in which TrkB is likely to play a role in initiation and metastasis of carcinomas. Overexpression of TrkB is often correlated with the tumorigenesis, angiogenesis and drug resistance in these malignancies, contributing significantly to the metastasis and aggressive phenotype of these poor prognosis tumors. The evidences to show the significant contribution of TrkB to malignancy not only came from solid tumors such as neoblastoma, pancreas cancer, Wilm's tumor and hepatocarcinoma, but also came from haematological malignancies such as Hodgkin lymphoma and multiple myeloma. In summary, besides its role in development and function of nervous system, TrkB is likely to also play a role in initiation and metastasis of carcinoma although it still remains to be further investigated and confirmed. Emerging data have suggested that TrkB may be a mediator as well as a marker of carcinogenesis and metastasis, therefore TrkB may be used as a valuable target for cancer therapy especially for the metastatic tumors with poor prognosis.

Biomarkers, Tumor↗

PubMed2006

Local feature analysis: a statistical theory for reproducible essential dynamics of large macromolecules.

Multivariate statistical methods are widely used to extract functional collective motions from macromolecular molecular dynamics (MD) simulations. In principal component analysis (PCA), a covariance matrix of positional fluctuations is diagonalized to obtain orthogonal eigenvectors and corresponding eigenvalues. The first few eigenvectors usually correspond to collective modes that approximate the functional motions in the protein. However, PCA representations are globally coherent by definition and, for a large biomolecular system, do not converge on the time scales accessible to MD. Also, the forced orthogonalization of modes leads to complex dependencies that are not necessarily consistent with the symmetry of biological macromolecules and assemblies. Here, we describe for the first time the application of local feature analysis (LFA) to construct a topographic representation of functional dynamics in terms of local features. The LFA representations are low dimensional, and like PCA provide a reduced basis set for collective motions, but they are sparsely distributed and spatially localized. This yields a more reliable assignment of essential dynamics modes across different MD time windows. Also, the intrinsic dynamics of local domains is more extensively sampled than that of globally coherent PCA modes.

Bacteriophage T4↗

PubMed2006

The gene controlling the quantitative trait locus EPITHIOSPECIFIER MODIFIER1 alters glucosinolate hydrolysis and insect resistance in Arabidopsis.

Glucosinolates are sulfur-rich plant secondary metabolites whose breakdown products have a wide range of biological activities in plant-herbivore and plant-pathogen interactions and anticarcinogenic properties. In Arabidopsis thaliana, hydrolysis by the enzyme, myrosinase, produces bioactive nitriles, epithionitriles, or isothiocyanates depending upon the plant's genotype and the glucosinolate's structure. A major determinant of this structural specificity is the epithiospecifier locus (ESP), whose protein causes the formation of epithionitriles and nitriles. A quantitative trait locus (QTL) on chromosome 3 epistatically affects nitrile formation in combination with ESP; this QTL has been termed EPITHIOSPECIFIER MODIFIER1 (ESM1). We identified a myrosinase-associated protein as the ESM1 QTL in Arabidopsis using map-based cloning with recombinant inbred lines, natural variation transcriptomic analysis, and metabolic profiling. In planta and in vitro analyses with natural ESM1 alleles, ESM1 knockouts, and overexpression lines show that ESM1 represses nitrile formation and favors isothiocyanate production. The glucosinolate hydrolysis profile change influenced by ESM1 is associated with the ability to deter herbivory by Trichoplusia ni. This gene could provide unique approaches toward improving human nutrition.

Animals↗

PubMed2006

Neurotoxicological consequence of long-term exposure to lanthanum.

Lanthanides, because of their diversified physical and chemical effects, have been widely used in a number of fields. As a result, more and more lanthanides are entering into the environment and eventually accumulated in human body. Recently, a new medicine, lanthanum carbonate (Fosrenol), has been used to treat chronic renal failure (CRF), and the dosage is much higher than the daily intake of lanthanides. However, the effects of lanthanides on human body, especially on the central nervous system, are still unclear. The aim of this study was to determine whether long-term lanthanum exposure results in persistent alternations in nervous system function. Wistar rats were exposed to lanthanum chloride (LaCl(3)) through oral administration at 0, 0.1, 2 and 40mg/kg concentration from 4 weeks through 6 months of age. Morris water maze test showed that lanthanum exposure at 40mg/kg could significantly impair the behavioral performance. To fully investigate the neurotoxicological consequence of lanthanum exposure, brain elemental distributions and neurochemicals were also investigated. The distributions of brain elements such as Ca, Fe and Zn were significantly altered after lanthanum exposure. Moreover, 40mg/kg LaCl(3) significantly inhibited the activity of Ca(2+)-ATPase; the function of the central cholinergic system was also noticeably disturbed and the contents of some monoamines neurotransmitters were significantly decreased. These findings indicate that chronic exposure to lanthanum could possibly impair the learning ability and this deficit may be possibly attributed to the disturbance of the homeostasis of trace elements, enzymes and neurotransmitter systems in brain. Therefore, the application of lanthanide, especially in pharmacology, should be cautious.

Acetylcholine↗

PubMed2006

Combinatorial search of thermoelastic shape-memory alloys with extremely small hysteresis width.

Reversibility of structural phase transformations has profound technological implications in a wide range of applications from fatigue life in shape-memory alloys (SMAs) to magnetism in multiferroic oxides. The geometric nonlinear theory of martensite universally applicable to all structural transitions has been developed. It predicts the reversibility of the transitions as manifested in the hysteresis behaviour based solely on crystal symmetry and geometric compatibilities between phases. In this article, we report on the verification of the theory using the high-throughput approach. The thin-film composition-spread technique was devised to rapidly map the lattice parameters and the thermal hysteresis of ternary alloy systems. A clear relationship between the hysteresis and the middle eigenvalue of the transformation stretch tensor as predicted by the theory was observed for the first time. We have also identified a new composition region of titanium-rich SMAs with potential for improved control of SMA properties.

Algorithms↗

PubMed2006

Delayed changes in T1-weighted signal intensity in a rat model of 15-minute transient focal ischemia studied by magnetic resonance imaging/spectroscopy and synchrotron radiation X-ray fluorescence.

Previous studies have found that rats subjected to 15-min transient middle cerebral artery occlusion (MCAO) show neurodegeneration in the dorsolateral striatum only, and the resulting striatal lesion is associated with increased T1-weighted (T1W) signal intensity (SI) and decreased T2-weighted (T2W) SI at 2-8 weeks after the initial ischemia. It has been shown that the delayed increase in T1W SI in the ischemic region is associated with deposition of paramagnetic manganese ions. However, it has been suggested that other mechanisms, such as tissue calcification and lipid accumulation, also contribute to the relaxation time changes. To clarify this issue, we measured changes in relaxation times, lipid accumulation, and elemental distributions in the brain of rats subjected to 15-min MCAO using MRI, in vivo 1H MR spectroscopy (MRS), and synchrotron radiation X-ray fluorescence (SRXRF). The results show that a delayed (2 weeks after ischemia) increase in T1W SI in the ischemic striatum is associated with significant increases in manganese, calcium, and iron, but without evident accumulation of MRS-visible lipids or hydroxyapatite precipitation. It was also found that 15-min MCAO results in acutely reduced N-acetylaspartate (NAA)/creatine (Cr) ratio in the ipsilateral striatum, which recovers to the control level at 2 weeks after ischemia.

Animals↗

PubMed2006

Downregulation of PIK3CB by siRNA suppresses malignant glioma cell growth in vitro and in vivo.

EGFR overexpression is the most frequent and important molecular event in the development of astrocytic gliomas, and the P13K signaling pathway is one of the most important downstream pathways of EGFR. EGFR and other members of the receptor tyrosine kinases (RTKs) family, such as VEGFR, PDGFR, and IGFR, et cetera, are often overexpressed in most of malignant gliomas and share common downstream signaling pathways. Therefore, it is considered that directly targeting the downstream PI3K pathway may be more effective in blocking multiple inputs. The PIK3CB gene encoding the class 1A PI3K catalytic subunit p110beta was selected as the target of therapeutic approach for malignant gliomas in the present study. Human U251 glioblastoma cells with high endogenous p110beta expression were transfected with plasmid-based siRNA targeting PIK3CB gene. It was found that downregulation of p110beta expression resulted in the suppression of cell proliferation, arrest of cell cycle, reduction of cell invasion, and promotion of cell apoptosis in vitro. In addition, the growth of the subcutaneous U251 glioma in the nude mice treated with siRNA targeting PIK3CB was significantly inhibited. These results demonstrate that PIK3CB overexpression may play an oncogenic role in the PI3K pathway, and the plasmid-based siRNA targeting of PIK3CB is a potential and promising approach for the treatment of malignant gliomas.

Animals↗

PubMed2006

Effect of iodine supplement on iodine status and 5'-deiodinase activity in the brain of neonatal rats with iodine deficiency.

The weanling Wistar rats of iodine deficiency were divided into three groups for supplementation of different levels of iodine (iodine-excessive [IE], iodine-adequate [IA], and iodine-deficient [ID]), with a control group (C). The iodine content in the thyroid was determined by epithermal neutron activation analysis. The activities of 5'-deiodinase and 5-deiodinase in the brains were assayed by determining the conversion ratios of T4 to T3 and rT3, respectively. The thyroid hormones levels in serum were also tested. The results indicated that the ID group had a goiter containing a small amount of iodine, but the IE group had a slightly swollen thyroid with rich iodine; the concentration of iodine per unit mass of thyroid was lower in group IE than in groups IA and C. The highest 5'-deiodinase and lowest 5-deiodinase activities in group ID and the lowest 5'-deiodinase activity in group IE were found. The iodine deficiency or excess resulted in a compensated hypothyroid state. The results suggest that the iodine status and the deiodinases activities would become normal for the rats of iodine deficiency if adequate iodine is supplemented soon after birth. Meanwhile, it is also critical to avoid excessive intake of iodine to reduce the risk for overcorrecting.

Animals↗

PubMed2006

[Contrast analysis of different sagittal split ramus osteotomy methods in correcting mandibular prognathism].

OBJECTIVE: To explore the indication, advantage and disadvantage of modified or classical technique of intraoral sagittal split ramus osteotomy (SSRO) for correction of mandibular prognathism. METHODS: From January 1997 to January 2005, 95 patients suffering from mandibular prognathism or accompanied by other deformities were treated with modified or classical technique of intraoral SSRO. Of 95 cases, there were 34 males and 61 females, aging 15 to 44 years, including 53 cases of single mandibular prognathism, 28 cases accompanied with mandibular deviation, 11 cases accompanied with maxillary retrognathism, 2 cases accompanied with glossacele and 1 case accompanied with malar protrusion. X-ray cephalometry showed: sella-nasion-A point (SNA) 80-83 degrees, sella-nasion-B point (SNB) 80-84 degrees, A point-nasion-B point (ANB)--3-1 degrees. Forty-three cases were corrected by modified SSRO and 52 cases by classical SSRO. RESULTS: The face appearance and dental articulation of all the patients were improved greatly. In patients by classical SSRO, disorder of local sensibility occurred in 9 cases, mandibular fracture during the cleavage of the ascending ramus in 1 case, significant bleeding in 1 case, postoperative infection in 1 case and postoperative relapse in 3 cases. In patients by modified SSRO, disorder of local sensibility occurred in 2 cases and postoperative relapse in 1 case; no mandibular fracture, significant bleeding, postoperative infection and other complications occurred. With a follow-up of 3 months to 7 years, X-ray cephalometry showed SNA 81-83 degrees, SNB 78-81 degrees and ANB 1-4 degrees. CONCLUSION: Modified SSRO is an ideal method of correcting mandibular prognathism, especially severer mandibular prognathism accompanied by mandible deviation deformity.

Adolescent↗

PubMed2006

[Prosthesis replacement of proximal humerus after resection of malignant tumor].

OBJECTIVE: To study the operative effect and complication of the prosthesis replacement of the proximal humerus with malignant tumor. METHODS: From October 1998 to August 2003, the prosthesis replacement was performed to treat the proximal femur with malignant tumor in 4 patients, including 2 patients with osteosarcoma (Enneking staging, I A) and 2 patients with giant cell tumor of the bone (II A, II B). By the International Society of Limb Salvage (ISOLS) criterion, the 2 cases of osteosarcoma were preoperatively scored as 4 and 5 points, and 2 cases of giant cell tumor of the bone were scored as 9 and 11 points. The patients' psychological conditions as well as their limb pain, shape, locality, activity, and function were also observed. RESULTS: The follow-up for 24-58 months (mean, 44 months) showed that there was no local recurrence or infection in all the patients except one patient who had the loosening of the screws for the fixation 17 months after operation and had no treatment. After operation, all the patients had a better postoperative extention angle from 22 degrees to 41 degrees (mean, 25 degrees), bending angle from 29 degrees to 80 degrees (mean, 35 degrees), abduction angle from 5 degrees to 28 degrees, and circumgyrate angle from 15 degrees to 22 degrees in their shoulder joints. However, the shoulder joint function was still unstable to some extent and the joints had a decreased strength. By the criterion formulated by the ISOLS, the postoperative score for assessing the 2 patients with osteosarcoma was increased by 16 points when compared with the preoperative score; the score for the 2 patients with giant cell tumor of the bone was increased by 9.5 points. CONCLUSION: The prosthesis replacement to treat the malignant tumor of the proximal humerus is the good method of choice and has a good therapeutic result; however, there are more complications and so the method should be cautiously employed in the clinical practice.

Adult↗

PubMed2005

Long-term effects of lanthanum intake on the neurobehavioral development of the rat.

The effects of subchronic exposure to lanthanum on rats' physical and neurobehavioral development were investigated. Wistar rats were exposed to lanthanum through oral administration at 0, 0.1, 2, and 40 mg/kg concentrations from gestation day 0 through 5 months of age. Prior to weaning of the pups, physical parameters and neurobehaviors were assessed, including body weight gain, pinna detachment, eye opening, surface righting reflex and swimming endurance. At 30 days of age, DNA concentration and protein/DNA ratio of the whole brain were determined. At 150 days of age, the Morris water maze test was carried out to study the memory and learning abilities of the rats. Differences were found in the body weight gain, surface righting reflex and swimming endurance. Moreover, lanthanum exposure significantly altered the DNA concentration and Protein/DNA in brain. The Morris water maze test showed that lanthanum exposure at 40 mg/kg significantly impaired memory and learning abilities. These findings indicate that lanthanum is a potential behavior teratogen. The information provided by this work should be considered in future applications of lanthanides.

Animals↗

PubMed2005

Phosphorylated alpha-actinin and protein-tyrosine phosphatase 1B coregulate the disassembly of the focal adhesion kinase x Src complex and promote cell migration.

The focal adhesion kinase (FAK) is a key regulator of cell migration. Phosphorylation at Tyr-397 activates FAK and creates a binding site for Src family kinases. FAK phosphorylates the cytoskeletal protein alpha-actinin at Tyr-12. Here we report that protein-tyrosine phosphatase 1B (PTP 1B) is an alpha-actinin phosphatase. PTP 1B-dependent dephosphorylation of alpha-actinin was seen in COS-7 cells and PTP 1B-null fibroblasts reconstituted with PTP 1B. Furthermore, we show that coexpression of wild-type alpha-actinin and PTP 1B causes dephosphorylation at Tyr-397 in FAK. No dephosphorylation was observed in cells coexpressing the alpha-actinin phosphorylation mutant Y12F and PTP 1B. Furthermore, the phosphorylation at four other sites in FAK was not altered by PTP 1B. In addition, we found that phosphorylated alpha-actinin bound to Src and reduced the binding of FAK to Src. The dephosphorylation at Tyr-397 in FAK triggered by wild-type alpha-actinin and PTP 1B caused a significant increase in cell migration. We propose that phosphorylated alpha-actinin disrupts the FAK x Src complex exposing Tyr-397 in FAK to PTP 1B. These findings uncover a novel feedback loop involving phosphorylated alpha-actinin and PTP 1B that regulates FAK x Src interaction and cell migration.

Actinin↗

PubMed2005

Performance and microbial structure of a combined biofilm reactor.

A novel combined biofilm reactor was established and applied as a single treatment unit for carbon and nitrogen removal of wastewater. The nitrogen removal performance of the reactor at different levels of organic carbon (COD) loading was investigated when the influent total nitrogen (TN) loading was 0.74 g TN/m2 day. Continuous experimental results demonstrated that 80% nitrogen was eliminated when the influent COD loading ranged between 2.06 g and 3.92 g COD/m2 day. Microbial composition in the reactor was analyzed using fluorescent in situ hybridization (FISH) and conventional batch tests. The relative abundance of ammonia-oxidizing bacteria in the aerobic zone of the reactor measured by FISH was consistent with the result from conventional batch tests.

Ammonia↗

PubMed2005

Distribution of ytterbium-169 in rat brain after intravenous injection.

It is well known that lanthanides have come into extensive and rapid use in a number of fields. As a result, more and more lanthanides are getting into the environment and food chains. However, the distributions of lanthanides in brain are not yet very clear. In this study, adult Sprague-Dawley male rats were intravenously injected with 0.5 ml of 169YbCl3 solution (containing 10 microg Yb). The brains were perfused with saline to minimize the blood influence. The radioactivities of 169Yb in the five brain regions (hypothalamus, cerebellum, hippocampus, corpus striatum and cerebral cortex) were counted. The results suggested that Yb did enter into the brain. Though only about 0.005% of the given dose was accumulated in the brain, Yb seemed to remain in the brain for long time. The highest specific activities were observed in the hypothalamus, hippocampus and cerebellum.

Animals↗

PubMed2005

Accumulation and distribution of samarium-153 in rat brain after intraperitoneal injection.

It is well known that rare earth elements (REEs) have come into extensive use in a number of fields. As a result, REEs are becoming closely related to human's daily life. However, until now, the distributions of REEs in the brain are not yet very clear. In this study, Sprague-Dawley male rats were intraperitoneally injected with 0.25 mL of (153)SmCl(3) solution (containing 10 microg Sm). The brains were perfused with saline to minimize the blood influence. The radioactivities of (153)Sm in the five brain regions (hypothalamus, cerebellum, hippocampus, corpus striatum, and cerebral cortex) were counted. The results suggested that Sm did enter into the brain. Although only about 0.0003% of the given dose was accumulated in the brain, Sm seemed to be remain in the brain for a long time. The highest amounts and lowest concentrations of (153)Sm were found in the cerebral cortex, and the highest concentrations of (153)Sm were found in the hypothalamus.

Animals↗

PubMed2005

[The system design of an intraperitoneal perfusion machine for hyperthermic chemotherapy based on single chip microcomputer].

A new kind of method for intraperitoneal hyperthermic chemotherapy has been proved to be very effective for the therapy of gastrointestinal cancer. In this article is reported an intraperitoneal perfusion machine which is designed for instituting the treatment. The liquor of the chemotherapy drug is infused into the abdomen after being heated by heating system; the liquor flows out of the abdomen is abandoned. The temperature of heating and the velocity of flow are controlled by MCU, thus the temperature of the liquor of the chemotherapy drug in the abdomen can be adjusted to the most favarable temperature.

Abdominal Cavity↗

PubMed2005

[Fabrication of 3-dimensional skull model with rapid prototyping technique and its primary application in repairing one case of cranio-maxillo-facial trauma].

OBJECTIVE: To investigate the methods of establishing 3-dimensional skull model using electron beam CT (EBCT) data rapid prototyping technique, and to discuss its application in repairing cranio-maxillo-facial trauma. METHODS: The data were obtained by EBCT continuous volumetric scanning with 1.0 mm slice at thickness. The data were transferred to work-station for 3-dimensional surface reconstruction by computer-aided design software and the images were saved as STL file. The data can be used to control a laser rapid-prototyping device (AFS-320QZ) to construct geometric model. The material for the model construction is a kind of laser-sensitive resin power, which will become a mass when scanned by laser beam. The design and simulation of operation can be done on the model. The image data were transferred to the device slice by slice. Thus a geometric model is constructed according to the image data by repeating this process. Preoperative analysis, surgery simulation and implant of bone defect could be done on this computer-aided manufactured 3D model. One case of cranio-maxillo-facial bone defect resulting from trauma was reconstructed with this method. The EBCT scanning showed that the defect area was 4 cm x 6 cm. The nose was flat and deviated to left. RESULTS: The 3-dimensional skull was reconstructed with EBCT data and rapid prototyping technique. The model can display the structure of 3-dimensional anatomy and their relationship. The prefabricated implant by 3-dimensional model was well-matched with defect. The deformities of flat and deviated nose were corrected. The clinical result was satisfactory after a follow-up of 17 months. CONCLUSION: The 3-dimensional model of skull can replicate the prototype of disease and play an important role in the diagnosis and simulation of operation for repairing cranio-maxillo-facial trauma.

Adult↗