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Biomedical subjects

Gang Cheng

Publications and source records attributed to Gang Cheng.

At least 19 recordsLinked to original sources
PubMed2026

Seawater immersion reshapes the temporal dynamics of traumatic brain injury and reveals mitochondrial oxidative stress as a modifiable therapeutic target.

Traumatic brain injury (TBI) evolves through time-dependent secondary injury, but whether seawater (SW) immersion merely amplifies pathology or reshapes the temporal trajectory of post-traumatic biology remains unclear. Here, we applied time-resolved proteomics to mouse brains after controlled cortical impact (CCI) with or without artificial SW immersion at 1, 3, 7, and 28 days post-injury. Trajectory-based proteomic analysis revealed that SW immersion altered the direction, magnitude, timing, persistence, and recovery of protein responses, rather than simply intensifying TBI-induced changes. This remodeled trajectory exhibited phase-specific patterns, including SW-dominant, synergistically enhanced, and attenuated responses, highlighting mitochondrial oxidative stress, inflammatory activation, complement/coagulation disturbance, and impaired structural repair. Phenotypic validation confirmed phase-specific deficits, including acute inflammatory-redox injury, impaired neuronal survival, chronic axon-myelin disruption, and incomplete behavioral recovery. SS-31 partially mitigated selected inflammatory, redox, neuronal, and white matter abnormalities, supporting mitochondrial oxidative stress as a modifiable node rather than the sole driver of trajectory remodeling. These findings identify seawater immersion as a temporal modifier of secondary injury and emphasize that environmental trauma may require trajectory-informed, phase-specific therapeutic interventions.

Animals↗
PubMed2007

Autophagy of vascular smooth muscle cells in atherosclerotic lesions.

Autophagy genes were first identified in the yeast system and some of their mammalian orthologues have also been characterized. Increasing lines of evidence indicate that various intracellular proteins, including G proteins, mammalian target of rapamycin (mTor) and Pl3K/Akt/PKB, of transmembrane signaling pathways are involved in the regulation of autophagy genes. We have recently discovered autophagy as a mechanism of cell death in atherosclerotic vascular smooth muscle cells (VSMCs). Tumor necrosis factor-alpha (TNF-alpha), insulin-like growth factor-1 (IGF-1), and 7-ketocholesterol can regulate the expression of autophagic genes, including microtubule-associated protein 1 light chain-3 (MAP1LC3) and Beclin 1, through Akt/PKB and c-jun N-terminal signal pathways in VSMCs. However, the balance between cell death and survival of VSMCs in the fibrous cap of atherosclerotic plaques appears to best correlate with plaque instability. Understanding the underlying cellular and molecular mechanisms of autophagy can provide key insights into the cell death machinery of atherosclerotic diseases.

Apoptosis Regulatory Proteins↗
PubMed2006

Involvement of chloride channels in IGF-I-induced proliferation of porcine arterial smooth muscle cells.

OBJECTIVE: The existence of Cl- channels in vascular smooth muscle cells (VSMCs) has been increasingly investigated, but the biological functions are not yet clear. Insulin-like growth factor (IGF)-I affects proliferation and migration of VSMCs, and dysregulation of this axis may be involved in atherogenesis and intimal hyperplasia. We examined the effects of Cl- channel blockers on IGF-I-induced proliferation in porcine VSMCs. The siRNA approach was used to support the role of ClC-2, a member of the volume-regulated Cl- channel family, in cell proliferation of VSMCs. METHODS AND RESULTS: The IGF-I-induced VSMC proliferation was significantly suppressed by the Cl- channel blockers NPPB and IAA94 but not by DIDS. IGF-I-induced cell proliferation parallels a significant increase in the endogenous expression of ClC-2 mRNA and protein. Inhibitors of PI3-kinase, LY294002 and wortmannin, significantly attenuated the IGF-I-upregulated ClC-2 expression and cell proliferation. We observed ClC-2-like Cl- current, and this current was augmented by IGF-I. SiRNA specifically targeted to ClC-2 abolished IGF-I-induced cell proliferation. CONCLUSION: Our data demonstrate that ClC-2 plays a role in IGF-1-induced regulation of VSMC proliferation in cardiovascular diseases.

Androstadienes↗
PubMed2006

Insulin-like growth factor-I receptors in atherosclerotic plaques of symptomatic and asymptomatic patients with carotid stenosis: effect of IL-12 and IFN-gamma.

The balance between apoptosis and survival of vascular smooth muscle cells (VSMCs) in the fibrous cap appears to best correlate with plaque instability or stability and is controlled by growth factors and cytokines. We recently reported the inhibition of insulin-like growth factor (IGF)-I-induced proliferation and increase in apoptosis of VSMCs by atheroma-associated cytokines. Here we assessed the expression of IGF-I receptor (IGF-IR) in atherosclerotic plaques and in plaque VSMCs of asymptomatic and symptomatic patients with carotid stenosis and examined the effect of IGF-I, IL-12, and IFN-gamma on the expression of IGF-IR and IGF-binding protein (IGFBP)-3 in plaque VSMCs. We observed significantly lower density of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic nuclei and increased positive immunoreactivity to IGF-IR and mRNA transcripts of endogenous IGF-I and IGF-IR in asymptomatic than in symptomatic plaque VSMCs. Positive correlation was found between apoptosis and IGF-IR expression in asymptomatic (r(2) = 0.942) and symptomatic (r(2) = 0.908) plaque VSMCs. The specific binding of (125)I-labeled IGF-I was 3.7-fold higher in plaque VSMCs of asymptomatic patients than in symptomatic patients. IGF-I increased both IGF-IR mRNA transcripts and expression of IGFBP-3 in VSMCs of asymptomatic plaques. IL-12 and IFN-gamma decreased IGF-IR mRNA transcripts and further increased the expression of IGFBP-3 in asymptomatic VSMCs but had no effect in symptomatic VSMCs. These data suggest that the decreased expression of IGF-IR mRNA and increased expression of IGFBP-3 in carotid plaques of symptomatic patients could be due to atheroma-associated cytokines and this could result in plaque instability.

Aged↗
PubMed2006

Electrochemically deposited organic luminescent films: the effects of deposition parameters on morphologies and luminescent efficiency of films.

The electropolymerization behaviors of an electroactive and luminescent compound TCPC as precursor are studied. The resultant electrochemical deposition (ED) films are characterized by cyclic voltammetry (CV), UV-vis, fluorescence spectra, scanning electron microscopy (SEM), and atomic force microscopy (AFM). Under the CV mode with potential range of -0.5 to 0.85 V vs Ag/Ag(+), the coupling reactions between the carbazole units of TCPC are very efficient, while the fluorescent trifluorene segment in TCPC is chemically inert in this potential range, which results in a highly fluorescent film formation on indium tin oxide (ITO) electrode. The deposition parameters for preparing the TCPC-based ED films are optimized, and the best ED film gives the fluorescence efficiency of 45.5% with surface roughness of 2.8 nm and morphologic stability as heating to 180 degrees C. The light-emitting devices (LEDs) using this ED film as light emitting layer with structure ITO/ED film (approximately 100 nm)/Ba/Al achieve maximum luminescence and external quantum efficiency of 4224 cd/m(2) at 17 V and 0.72% at 11.5 V, respectively, which are better than the device using TCPC spin-coating films as emitting layer. The technique provides a facile route toward a patternable luminescent film and device because such luminescent ED films can be manipulatively deposited on the electrified electrode.

Journal Article↗
PubMed2006

Highly luminescent network films from electrochemical deposition of peripheral carbazole functionalized fluorene oligomer and their applications for light-emitting diodes.

Highly luminescent network films on flat indium tin oxide (ITO) substrates are prepared by electropolymerization using an electroactive and fluorescent compound as precursor; the LEDs prepared using these films as a light emitting layer achieve the maximum luminance and external quantum efficiency of 4224 cd/m(2) and 0.72%, respectively, which demonstrates that electrochemical synthesis can be a new route to construct the highly luminescent films.

Journal Article↗
PubMed2006

The hypothalamic supraoptic and paraventricular nuclei of the echidna and platypus.

The monotremes are an intriguing group of mammals that have major differences in their reproductive physiology and lactation from therian mammals. Monotreme young hatch from leathery skinned eggs and are nourished by milk secreted onto areolae rather than through nipples. Parturition and lactation are in part controlled through the paraventricular and supraoptic nuclei of the hypothalamus. We have used Nissl staining, enzyme histochemistry, immunohistochemistry for tyrosine hydroxylase, calbindin, oxytocin, neurophysin and non-phosphorylated neurofilament protein, and carbocyanine dye tracing techniques to examine the supraoptic and paraventricular nuclei and the course of the hypothalamo-neurohypophysial tract in two monotremes: the short-beaked echidna (Tachyglossus aculeatus) and the platypus (Ornithorhynchus anatinus). In both monotremes, the supraoptic nucleus consisted of loosely packed neurons, mainly in the retrochiasmatic position. In the echidna, the paraventricular nucleus was quite small, but had similar chemoarchitectural features to therians. In the platypus, the paraventricular nucleus was larger and appeared to be part of a stream of magnocellular neurons extending from the paraventricular nucleus to the retrochiasmatic supraoptic nucleus. Immunohistochemistry for non-phosphorylated neurofilament protein and carbocyanine dye tracing suggested that hypothalamo-neurohypophysial tract neurons in the echidna lie mainly in the retrochiasmatic supraoptic and lateral hypothalamic regions, but most neurophysin and oxytocin immunoreactive neurons in the echidna were found in the paraventricular, lateral hypothalamus and supraoptic nuclei and most oxytocinergic neurons in the platypus were distributed in a band from the paraventricular nucleus to the retrochiasmatic supraoptic nucleus. The small size of the supraoptic nucleus in the two monotremes might reflect functional aspects of monotreme lactation.

Acetylcholinesterase↗
PubMed2006

Distribution characteristics of orally administered olamufloxacin, a newly synthesized fluoroquinolone antibacterial, in lung epithelial lining fluid and alveolar macrophage in rats.

This study described distribution characteristics of olamufloxacin (HSR-903) in lung epithelial lining fluid (ELF) and alveolar macrophage (AM) in rats, two important representative infectious sites in lower respiratory tract infections. The rats were orally administered at a dose of 10mg/kg. At each designated time, rats were sacrificed, and blood samples were collected from the superior vena cava, and ELF and AM samples were gathered by the bronchoalveolar lavage method. The AUC ratios of ELF/plasma and AM/plasma of HSR-903 were 3.03+/-0.54 and 97.5+/-24.2, respectively, notably higher than those of ciprofloxacin (CPFX). Kinetic analyses of concentration-time profiles of HSR-903 in ELF and AM indicated that the influx clearance from plasma to ELF across the alveolar barrier was 5.8-fold higher than the efflux clearance from ELF. Furthermore, the permeability of HSR-903 across the cultured AM plasma membrane was 5.5 and 14.5 times greater than those of CPFX and pipemidic acid (PPA), respectively. A significant correlation (r2 = 0.995) was achieved between permeability across AM plasma membrane and hydrophobicity, implying that passage through AM membrane was principally involved in the passive diffusion. The extent of AM intracellular binding was the greatest for grepafloxacin, followed by HSR-903, CPFX, levofloxacin and PPA. In conclusion, HSR-903 distributed more efficiently in ELF and AM than CPFX, and the high accumulation of HSR-903 by AM cells may be accounted for by both the high transferability across the AM membrane and avid binding to the membrane phospholipids.

Administration, Oral↗
PubMed2006

Development of the human nucleus of the solitary tract: a cyto- and chemoarchitectural study.

The present study investigated the prenatal development of the cyto- and chemoarchitecture of the human nucleus of the solitary tract from 9 to 35 weeks, by using Nissl staining and immunoreactivity to calbindin, calretinin, tyrosine hydroxylase and GAP-43. The nucleus began to gain heterogeneity and show different subnuclei as early as 13 weeks, and approached cytoarchitectural maturation from 21 to 25 weeks. The subnuclear division pattern observed in the fetal nucleus of the solitary tract at 25 weeks was very similar to that of the adult. Neurons immunoreactive to calbindin first appeared in the medial gastrointestinal area of the nucleus at 13 weeks, particularly within a putative gelatinosus subnucleus, while calretinin immunoreactivity during fetal life suggested the possible presence of a central subnucleus. Tyrosine hydroxylase immunoreactive neurons were seen in the medial subdivisions of the nucleus of the solitary tract as early as 13 weeks, but the population continued to increase until 25 weeks. Strong GAP-43 immunoreactivity was also present in the nucleus of the solitary tract at 13 weeks, especially in the dorsolateral and commissural subnuclei, while at 21 weeks there was a significant decline of GAP-43 expression. Results from the chemoarchitectural study showed that the human nucleus of the solitary tract expressed various neurochemical substances at an early developmental age (13 weeks), even before cellular and neuropil maturation was fully attained. Expression of these factors may play an important role in establishment and integration of viscerosensory function in the nucleus.

Aborted Fetus↗
PubMed2006

Expressed proteome analysis of human hepatocellular carcinoma in nude mice (LCI-D20) with high metastasis potential.

We report for the first time an expressed proteome for human hepatocellular carcinoma (HCC) in nude mice model. Most cases of human liver cancer are HCC with highly metastatic ability. Therefore, the early prediction or diagnosis and effective treatment are the key points of research. We have previously successfully established a human HCC nude mice model (LCI-D20) with high metastasis potential. To understand better the tumor biology of HCC it is worth to explore the relativity of all expressed protein profiles in the LCI-D20 HCC nude mice model. With advanced proteomics technologies, we have carried out a proteomic analysis with following stages: protein sample preparation of cancer tissue, including total cellular extraction and sequential fractionation, 2-DE and 2-D LC separation, ESI/MALDI-MS/MS identification, as well as data-dependent bioinformatics. The identified proteins were classified bioinformatically respective to their function, biological process and intracellular localization. Some important proteins found in HCC, e.g. metabolism enzymes, proteins regulating cell motility, signaling proteins, and heat shock proteins, are discussed in terms of their metastasis.

Animals↗
PubMed2006

Differential effects of insulin-like growth factor-1 and atheroma-associated cytokines on cell proliferation and apoptosis in plaque smooth muscle cells of symptomatic and asymptomatic patients with carotid stenosis.

Morbidity and mortality from atherosclerosis are associated with complicated atherosclerotic lesions due to plaque rupture, which is regulated by a balance between proliferation and apoptosis of vascular smooth muscle cells (VSMC). We examined insulin-like growth factor-1 (IGF-1)-induced survival of plaque VSMC from carotid endarterectomy specimens and investigated the underlying cellular mechanisms in the presence and absence of IL-12 and IFN-gamma. Both IL-12 and IFN-gamma were strongly expressed in symptomatic atherosclerotic plaques as compared with asymptomatic plaques. In asymptomatic plaque VSMC, IGF-1 induced the survival and proliferation of VSMC and accelerated VSMC into S-phase. IL-12 or IFN-gamma inhibited proliferation and VSMC were arrested in the G0-G1 phase. IGF-1 markedly inhibited the expression of p27(kip) and p21(cip) and significantly induced cyclin E and cyclin D. Both cytokines by themselves increased the expression of p27(kip) and p21(cip) and inhibited cyclin E and cyclin D. On the contrary, in symptomatic VSMC there was already increased apoptosis of VSMC and there was no significant effect of IGF-1 or inflammatory cytokines on proliferation, apoptosis or the expression of p27(kip) and p21(cip) and cyclin D and E. These data suggest that IGF-1 is more potent in inducing the survival of VSMC from the endarterectomy specimens of asymptomatic patients as compared to that of symptomatic subjects and cytokines associated with atheroma lesions decrease the activity of IGF-1-induced survival in the VSMC of asymptomatic plaques. The different expression and activity of cell cycle regulatory proteins could be responsible for apoptosis of VSMC and destabilization of atherosclerotic plaques.

Aged↗
PubMed2006

Insulin-like growth factor-1 and TNF-alpha regulate autophagy through c-jun N-terminal kinase and Akt pathways in human atherosclerotic vascular smooth cells.

A balance between programmed cell death and survival of vascular smooth muscle cells (VSMC) in the fibrous cap, which is primarily composed of VSMC and extracellular matrix, appears to best correlate with plaque instability or stability and is controlled by growth factors and cytokines. Autophagy is also involved in programmed cell death. We assessed the effect of TNF-alpha and insulin-like growth factor-1 (IGF-1) on the expression of autophagic genes, microtubule-associated protein 1 light chain 3 (MAPLC-3) and Beclin-1 in VSMC isolated from atherosclerotic plaques. Transmission electron microscopy showed a significantly higher number of vacuolated cells in the TNF-alpha-treated VSMC and a markedly lower number in the IGF-1-treated VSMC when compared with the untreated control group. TNF-alpha-induced MAPLC-3 mRNA expression through c-jun N-terminal kinase and protein kinase B pathways and induced Beclin-1 protein expression through the c-jun N-terminal kinase pathway. Expression of MAPLC-3 and Beclin-1 correlated with autophagic cell death of plaque VSMC. IGF-1 inhibited MAPLC-3 mRNA transcripts through the Akt pathway. These findings suggest that the expression of autophagy genes can be influenced by IGF-1 and TNF-alpha through c-jun N-terminal kinase or Akt pathways and autophagy might be involved in the regulation of plaque stability.

Apoptosis Regulatory Proteins↗
PubMed2006

Purification and characterization of TrzF: biuret hydrolysis by allophanate hydrolase supports growth.

TrzF, the allophanate hydrolase from Enterobacter cloacae strain 99, was cloned, overexpressed in the presence of a chaperone protein, and purified to homogeneity. Native TrzF had a subunit molecular weight of 65,401 and a subunit stoichiometry of alpha(2) and did not contain significant levels of metals. TrzF showed time-dependent inhibition by phenyl phosphorodiamidate and is a member of the amidase signature protein family. TrzF was highly active in the hydrolysis of allophanate but was not active with urea, despite having been previously considered a urea amidolyase. TrzF showed lower activity with malonamate, malonamide, and biuret. The allophanate hydrolase from Pseudomonas sp. strain ADP, AtzF, was also shown to hydrolyze biuret slowly. Since biuret and allophanate are consecutive metabolites in cyanuric acid metabolism, the low level of biuret hydrolase activity can have physiological significance. A recombinant Escherichia coli strain containing atzD, encoding cyanuric acid hydrolase that produces biuret, and atzF grew slowly on cyanuric acid as a source of nitrogen. The amount of growth produced was consistent with the liberation of 3 mol of ammonia from cyanuric acid. In vitro, TrzF was shown to hydrolyze biuret to liberate 3 mol of ammonia. The biuret hydrolyzing activity of TrzF might also be physiologically relevant in native strains. E. cloacae strain 99 grows on cyanuric acid with a significant accumulation of biuret.

Allophanate Hydrolase↗
PubMed2006

A novel alphaB-crystallin mutation associated with autosomal dominant congenital lamellar cataract.

PURPOSE: To identify the mutation and the underlying mechanism of cataractogenesis in a five-generation autosomal dominant congenital lamellar cataract family. METHODS: Nineteen mutation hot spots associated with autosomal dominant congenital cataract have been screened by PCR-based DNA sequencing. Recombinant wild-type and mutant human alphaB-crystallin were expressed in Escherichia coli and purified to homogeneity. The recombinant proteins were characterized by far UV circular dichroism, intrinsic tryptophan fluorescence, Bis-ANS fluorescence, multiangle light-scattering, and the measurement of chaperone activity. RESULTS: A novel missense mutation in the third exon of the alphaB-crystallin gene (CRYAB) was found to cosegregate with the disease phenotype in a five-generation autosomal dominant congenital lamellar cataract family. The single-base substitution (G-->A) results in the replacement of the aspartic acid residue by asparagine at codon 140. Far UV circular dichroism spectra indicated that the mutation did not significantly alter the secondary structure. However, intrinsic tryptophan fluorescence spectra and Bis-ANS fluorescence spectra indicated that the mutation resulted in alterations in tertiary and/or quaternary structures and surface hydrophobicity of alphaB-crystallin. Multiangle light-scattering measurement showed that the mutant alphaB-crystallin tended to aggregate into a larger complex than did the wild-type. The mutant alphaB-crystallin was more susceptible than wild-type to thermal denaturation. Furthermore, the mutant alphaB-crystallin not only lost its chaperone-like activity, it also behaved as a dominant negative which inhibited the chaperone-like activity of wild-type alphaB-crystallin. CONCLUSIONS: These data indicate that the altered tertiary and/or quaternary structures and the dominant negative effect of D140N mutant alphaB-crystallin underlie the molecular mechanism of cataractogenesis of this pedigree.

Adult↗
PubMed2006

Effect of matrine and carvedilol on collagen and MMPs activity of hypertrophy myocardium induced by pressure overload.

OBJECTIVE: To explore the effect and mechanism of matrine (Mt.) on myocardial interstitial fibrosis induced by pressure overload. METHODS: Pressure overloaded myocardial hypertrophy was produced by banding of aorta abdominalis in 67 male Sprague-Dawley rats weighing (200+/-15) g. The rats were assigned into one of the following groups: sham-operation control, operation control, operation group treated with matrine (15 mg/(kg.d)) and treated with carvedilol (Car.) (3.6 mg/(kg.d)) group. The rats were given drugs one day after operation. Five weeks after treatment, the left ventricular weight (LVW) was measured and the volume of myocardial cells was detected with Hematoxylin-Eosin (H-E) stain and Masson stain was used to assess the level of fibrosis of the myocardial matrix. Myocardial metalloproteinase activity was quantified with zymography, and survival rate was calculated. RESULTS: Survival rate significantly decreased (P<0.05), LVW/BW (body weight), MMP-2 (matrix metalloproteinase-2) activity (P<0.05), size of cardiomyocytes and interstitial fibrosis obviously increased in the operation group compared with sham control group. Mt. and Car. treatment can significantly increase survival rate (P<0.05), decrease LVW/BW (P<0.05) and MMP-2 activity (P<0.05), decrease size of cardiomyocytes and interstitial fibrosis compared with operation group. But there was difference compared with sham group. CONCLUSION: Matrine was shown to be able to prevent cardiac remodelling of hypertrophy cardium induced by pressure overload including myocardial hypertrophy and fibrosis which may be associated with the decrease in MMP-2 activity of heart.

Alkaloids↗
PubMed2006

Effect of radiofrequency catheter ablation on endothelial function and oxidative stress.

OBJECTIVE: Thromboembolic complications commonly occur in radiofrequency (RF) ablation procedures. Endothelial injury is believed to be induced during the process of RF ablation and to be involved in the mechanisms of thromboembolism. In this study, we gave further information about endothelial injury and also investiged the possible reasons for endothelial dysfunction during RF. METHODS AND RESULTS: Plasma levels of nitric oxide (NO), a biomarker of endothelial injury and some antioxidants and oxidants: beta-carotene (beta-CAR), lipoperoxide (LPO), superoxide dismutase (SOD), vitamin C (VC) and vitamin E (VE) were measured in 44 patients who underwent radiofrequency catheter ablation. Plasma NO concentration decreased significantly from 433.27 +/- 59.93 nmol/L to 407.13 +/- 52.32 nmol/L during RF ablation. Levels of beta-CAR, LPO, SOD,VC and VE were not significantly different. The decrease of plasma NO level was significantly correlated with ablation duration and cumulative ablation energy but had no significant correlation with overall procedure time, output ablation energy, ablation temperature and age of the patients. CONCLUSIONS: Radiofrequency catheter ablation induced endothelial injury but had no effect on oxidative stress. Radiofrequency energy was the main factor that caused endothelial injury during RF ablation.

Adult↗
PubMed2006

[Therapeutic effect of glucose-6-phosphate polyclonal antibody on vasogenic brain edema in rats].

OBJECTIVE: To observe the therapeutic effect of glucose-6-phosphate polyclonal antibody (G-6-P pAb) on vasogenic brain edema (VBE) in rats. METHODS: Sixty Wistar rats were randomly divided into normal control group, VBE group, mannitol-treated edema group, and G-6-P pAb-treated edema group. After establishment of rat models of VBE by intraperitoneal injection of phenylephrine in the latter 3 groups, mannitol was injected through the femoral vein in mannitol group and G-6-P pAb injected intraperitoneally in G-6-P pAb group. The permeability of the blood-brain barrier (BBB) was determined by Evans blue (EB) extravasation method, and the brain water content in the gray and white matter measured with a moisture analyzer. RESULTS: G-6-P pAb administration significantly reduced the permeability of BBB as well as the water content in the white matter in comparison with mannitol treatment (P<0.01), but the two treatments showed no obvious difference in reducing the water content in the gray matter (P>0.05). CONCLUSION: Changes in G-6-P activity results in BBB permeability alteration in the condition of VBE, and G-6-P pAb has a selective therapeutic effect against VBE, especially white matter edema.

Animals↗