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Kang Cheng

Publications and source records attributed to Kang Cheng.

At least 19 recordsLinked to original sources
PubMed2006

Physics models of centriole replication.

Our previous pre-clinic experimental results have showed that the epithelialization can be enhanced by the externally applied rectangular pulsed electrical current stimulation (RPECS). The results are clinically significant for patients, especially for those difficult patients whose skin wounds need long periods to heal. However, the results also raise questions: How does the RPECS accelerate the epithelium cell proliferation? To answer these questions, we have previously developed several models for animal cells, in a view of physics, to explain mechanisms of mitosis and cytokinesis at a cellular level, and separation of nucleotide sequences and the unwinding of a double helix during DNA replication at a bio-molecular level. In this paper, we further model the mechanism of centriole replication during a natural and normal mitosis and cytokinesis to explore the mechanism of epithelialization enhanced with the externally applied RPECS at a bio-molecular level. Our models suggest: (1) Centriole replication is an information flowing. The direction of the information flowing is from centrioles to centrioles based on a cylindrical template of 9 x 3 protein microtubules (MTs) pattern. (2) A spontaneous and strong electromagnetic field (EMF) force is a pushing force that separates a mother and a daughter centrioles in centrosomes or in cells, while a pulling force of interacting fibers and pericentriolar materials delivers new babies. The newly born babies inherit the pattern information from their mother(s) and grow using microtubule fragments that come through the centrosome pores. A daughter centriole is always born and grows along stronger EMF. The EMF mostly determines centrioles positions and plays key role in centriole replication. We also hypothesize that the normal centriole replication could not been disturbed in centrosome in the epithelium cells by our RPECS, because the centrioles have two non-conducting envelope (cell and centrosome membranes), that protect the normal duplication. The induced electric field by externally applied RPECS could be mild compared with the spontaneous and natural electric field of the centrioles. Therefore, the centriole replication during the epithelium cellular proliferation may be directly, as well as indirectly (e.g., somatic reflex) accelerated by the RPECS.

Cell Division↗
PubMed2006

Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans.

Nicotinic acid (NA) is commonly used to treat dyslipidemia, but it elicits an adverse effect, termed flushing, which consists of cutaneous vasodilation with associated discomfort. An animal model of NA-induced flushing has been established in mice. As in humans, NA stimulated vasodilation in a dose-dependent manner, was associated with an increase of the vasodilatory prostaglandin (PG) D2 in plasma and could be blocked by pretreatment with aspirin. Two PGD2 receptors have been identified: PGD2 receptor 1 (DP1, also called DP) and PGD2 receptor 2 (DP2, sometimes termed CRTH2). DP2 does not mediate NA-induced vasodilation; the DP2-specific agonist DK-PGD2 (13,14-dihydro-15-keto-PGD2) did not induce cutaneous vasodilation, and DP2-/- mice had a normal vasodilatory response to NA. By contrast, BW245C, a DP1-selective agonist, induced vasodilation in mice, and MK-0524, a DP1-selective antagonist, blocked both PGD2- and NA-induced vasodilation. NA-induced vasodilation was also studied in DP1+/+, DP1+/-, and DP1-/- mice; although NA-induced vasodilation depended almost completely on DP1 in female mice, it depended only partially on DP1 in male mice. The residual NA-induced vasodilation in male DP-/- mice was aspirin-sensitive. Thus, in the mouse, DP1 appears to be an important component involved in NA-induced vasodilation, but other cyclooxygenase-dependent mechanisms also may be involved. A clinical study in healthy men and women demonstrated that treatment with MK-0524 reduced the symptoms of flushing and the increase in skin perfusion after the administration of NA. These studies suggest that DP1 receptor antagonism may be an effective means to suppress NA-induced flushing in humans.

Adolescent↗
PubMed2006

Identification of transplanted human cells in animal tissues.

The potential of cell and gene therapy has generated extensive interest over the past several years. More recently, identification of stem cells of various types, especially embryonic stem cells, reinforced this interest. Systematic studies are now being launched to define the biology of various stem cells, including after transplantation of cells in mmunodeficient animals. This requires robust and unequivocal means to identify transplanted cells. Ideally, it should be possible to screen animal tissues for human cells with relatively simpler methods, followed by more precise localization of transplanted cells. We describe the application of conserved primate Charcot-Marie-Tooth disease type 1A repeat element for polymerase chain reaction-based screening of animal tissues for human cells. Similarly, direct polymerase chain reaction labeling of pancentromeric human alphoid sequences with digoxigenin-UTP generates in situ hybridization probes for identifying transplanted human cells. This pancentromeric probe identifies human cells irrespective of the original tissue source and can be combined with additional in situ methods to analyze cell differentiation. Incorporation of these strategies will facilitate translational studies aimed at understanding mechanisms concerning the trafficking, engraftment, proliferation, differentiation and function of human stem cells in animals.

Animals↗
PubMed2005

Electromagnetic field effect on separation of nucleotide sequences and unwinding of a double helix during DNA replication.

Our previous pre-clinic experimental results have showed that the bacterium infection can be suppressed and the epithelialization can be enhanced by the externally applied rectangular pulsed electrical current stimulation (RPECS). The results are clinically significant for patients, especially for those difficult patients whose skin wounds need long periods to heal. However, the results also raise questions: How does the RPECS accelerate the epithelium cell proliferation? What is the relationship among the bacterium infection, the epithelialization and the RPECS? To answer these questions, we have previously modeled mitosis and cytokinesis mechanisms for animal cells and amitosis for bacteria at a cellular level and in a view of physics. In this paper, we model the separation of nucleotide sequences and the unwinding of a double helix during DNA replication at a molecular level and also in wild types of cells. Firstly, we define a new concept of nucleotide (NT) electromagnetic field (EMF) box (sequence) which carries genetic information: The continuous NT EMF boxes compose a nucleotide strand. Then, we hypothesize the symmetry, repulsion and attraction of NT EMF boxes: If a pair of NT EMF boxes are (quasi) mirror or complementary symmetric about a plane (curve) or point, they repulse or attract from each other because there is a repulsive or attractive EMF force between them. Our models suggest, the repulsive EMF force from children DNA strands simultaneously separates the children DNA strands, splits the hydrogen bonds of parental base pairs, and unwinds the parental double helix while DNA polymerases are synchronously synthesizing the new children DNA strands. To understand the mechanism of epithelialization enhanced with the externally applied RPECS at a molecular level, we hypothesize that the normal separation of nucleotide sequences and unwinding of a double helix during DNA replication could be suppressed in the bacteria but not in the epithelium cells because: (a) the spontaneous EMF in the epithelium could be 1000 times stronger than that in bacteria; (b) the epithelium cells have one more non-conducting envelope (nuclear membrane) to protect the normal separation and unwinding; (c) based on our previous experimental data, the RPECS amount received by the bacteria are three times as much as the amount the epithelium cells receive. Therefore, the epithelium cellular proliferation may be directly, as well as indirectly (e.g., somatic reflex) accelerated by the RPECS.

Cell Proliferation↗
PubMed2005

Contrast adaptation and representation in human early visual cortex.

The human visual system can distinguish variations in image contrast over a much larger range than measurements of the static relationship between contrast and response in visual cortex would suggest. This discrepancy may be explained if adaptation serves to re-center contrast response functions around the ambient contrast, yet experiments on humans have yet to report such an effect. By using event-related fMRI and a data-driven analysis approach, we found that contrast response functions in V1, V2, and V3 shift to approximately center on the adapting contrast. Furthermore, we discovered that, unlike earlier areas, human V4 (hV4) responds positively to contrast changes, whether increments or decrements, suggesting that hV4 does not faithfully represent contrast, but instead responds to salient changes. These findings suggest that the visual system discounts slow uninformative changes in contrast with adaptation, yet remains exquisitely sensitive to changes that may signal important events in the environment.

Adaptation, Physiological↗
PubMed2005

11beta-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice.

The enzyme 11beta-hydroxysteroid dehydrogenase (HSD) type 1 converts inactive cortisone into active cortisol in cells, thereby raising the effective glucocorticoid (GC) tone above serum levels. We report that pharmacologic inhibition of 11beta-HSD1 has a therapeutic effect in mouse models of metabolic syndrome. Administration of a selective, potent 11beta-HSD1 inhibitor lowered body weight, insulin, fasting glucose, triglycerides, and cholesterol in diet-induced obese mice and lowered fasting glucose, insulin, glucagon, triglycerides, and free fatty acids, as well as improved glucose tolerance, in a mouse model of type 2 diabetes. Most importantly, inhibition of 11beta-HSD1 slowed plaque progression in a murine model of atherosclerosis, the key clinical sequela of metabolic syndrome. Mice with a targeted deletion of apolipoprotein E exhibited 84% less accumulation of aortic total cholesterol, as well as lower serum cholesterol and triglycerides, when treated with an 11beta-HSD1 inhibitor. These data provide the first evidence that pharmacologic inhibition of intracellular GC activation can effectively treat atherosclerosis, the key clinical consequence of metabolic syndrome, in addition to its salutary effect on multiple aspects of the metabolic syndrome itself.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2005

(D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G.

As a treatment for dyslipidemia, oral doses of 1-3 grams of nicotinic acid per day lower serum triglycerides, raise high density lipoprotein cholesterol, and reduce mortality from coronary heart disease (Tavintharan, S., and Kashyap, M. L. (2001) Curr. Atheroscler. Rep. 3, 74-82). These benefits likely result from the ability of nicotinic acid to inhibit lipolysis in adipocytes and thereby reduce serum non-esterified fatty acid levels (Carlson, L. A. (1963) Acta Med. Scand. 173, 719-722). In mice, nicotinic acid inhibits lipolysis via PUMA-G, a Gi/o-coupled seven-transmembrane receptor expressed in adipocytes and activated macrophages (Tunaru, S., Kero, J., Schaub, A., Wufka, C., Blaukat, A., Pfeffer, K., and Offermanns, S. (2003) Nat. Med. 9, 352-355). The human ortholog HM74a is also a nicotinic acid receptor and likely has a similar role in anti-lipolysis. Endogenous levels of nicotinic acid are too low to significantly impact receptor activity, hence the natural ligands(s) of HM74a/PUMA-G remain to be elucidated. Here we show that the fatty acid-derived ketone body (D)-beta-hydroxybutyrate ((D)-beta-OHB) specifically activates PUMA-G/HM74a at concentrations observed in serum during fasting. Like nicotinic acid, (D)-beta-OHB inhibits mouse adipocyte lipolysis in a PUMA-G-dependent manner and is thus the first endogenous ligand described for this orphan receptor. These findings suggests a homeostatic mechanism for surviving starvation in which (D)-beta-OHB negatively regulates its own production, thereby preventing ketoacidosis and promoting efficient use of fat stores.

3-Hydroxybutyric Acid↗
PubMed2005

Increased hypercholesterolemia and atherosclerosis in mice lacking both ApoE and leptin receptor.

Diabetes mellitus is one of the major risk factors associated with atherosclerosis and coronary heart disease but the mechanistic links between the disease and atherosclerosis are not well understood. In this study, we investigated the effect of the deletion of the long-form leptin receptor on the progression of atherosclerosis in ApoE-/- mouse. ApoE-/-;db/db double knockout mice as well as ApoE-/-;db/+ and ApoE-/- littermates were generated by crossing ApoE-/- and db/+ mice. On a regular chow diet, ApoE-/-;db/db mice at 20 weeks of age exhibited features typical of type 2 diabetes: obesity, hyperglycemia, hyperinsulinemia and dyslipidemia and had significantly accelerated atherosclerosis compared with their age-matched ApoE-/- littermates as assessed by either the percentage of the aorta bearing lesion (5.3+/-0.9% for ApoE-/-;db/db versus 1.5+/-0.5% for ApoE-/-) or by aortic lipid content ( approximately 1.5-2-fold increase in free cholesterol and approximately 3-4-fold increase in cholesteryl ester). The atherosclerosis in these ApoE-/-;db/db mice was further accelerated by feeding mice with a Western diet and markedly inhibited by fenofibrate with a 2.5- and 5.3-fold reduction of the lesion in male and female mice, respectively. The results from this study demonstrate that type 2 diabetes can accelerate atherogenesis in mice. This mouse model may provide insight into the mechanistic link between type 2 diabetes and atherosclerosis as well as serve as a valuable tool for evaluating therapeutics.

Animals↗
PubMed2005

3-D physical models of amitosis (cytokinesis).

Based on Newton's laws, extended Coulomb's law and published biological data, we develop our 3-D physical models of natural and normal amitosis (cytokinesis), for prokaryotes (bacterial cells) in M phase. We propose following hypotheses: Chromosome rings exclusion: No normally and naturally replicated chromosome rings (RCR) can occupy the same prokaryote, a bacterial cell. The RCR produce spontaneous and strong electromagnetic fields (EMF), that can be alternated environmentally, in protoplasm and cortex. The EMF is approximately a repulsive quasi-static electric (slowly variant and mostly electric) field (EF). The EF forces between the RCR are strong enough, and orderly accumulate contractile proteins that divide the procaryotes in the cell cortex of division plane or directly split the cell compartment envelope longitudinally. The radial component of the EF forces could also make furrows or cleavages of procaryotes. The EF distribution controls the protoplasm partition and completes the amitosis (cytokinesis). After the cytokinesis, the spontaneous and strong EF disappear because the net charge accumulation becomes weak, in the protoplasm. The exclusion is because the two sets of informative objects (RCR) have identical DNA codes information and they are electro magnetically identical, therefore they repulse from each other. We also compare divisions among eukaryotes, prokaryotes, mitochondria and chloroplasts and propose our hypothesis: The principles of our models are applied to divisions of mitochondria and chloroplasts of eucaryotes too because these division mechanisms are closer than others in a view of physics. Though we develop our model using 1 division plane (i.e., 1 cell is divided into 2 cells) as an example, the principle of our model is applied to the cases with multiple division planes (i.e., 1 cell is divided into multiple cells) too.

Bacteria↗
PubMed2004

Identification of neutral 4-O-alkyl quinolone nonpeptide GnRH receptor antagonists.

A series of neutral, nonbasic quinolone GnRH antagonists were prepared via Mitsunobu alkylation of protected and unprotected 4-hydroxy quinolone intermediates. The synthetic route was improved by utilization of unique reactivity and convergency afforded by the use of mono and bis-trimethylsilylethyl protected quinolones. Potent neutral GnRH antagonists were identified, including ether and lactam derivatives, that show similar in vitro binding affinity and functional activity as compared to the earlier basic 4-aminoalkyl quinolone series of nonpeptide GnRH antagonists.

Humans↗
PubMed2004

Syntheses and structure-activity relationship studies of piperidine-substituted quinolones as nonpeptide gonadotropin releasing hormone antagonists.

Syntheses and structure-activity relationships of piperidine-substituted quinolones as nonpeptide gonadotropin releasing hormone antagonists are described. Some of substituents on the piperidine ring that were investigated included a fused phenyl group, a (6R)-trifluoromethyl group, (6S) and (6R)-methyl group. This study showed that GnRH binding potency was tolerated by a small group at the 6-position of the piperidine, and blocking the 6-position by a trifluoromethyl group reduced clearance rate and increased oral bioavailability.

Animals↗
PubMed2004

3-D physical models of mitosis (with asters) and cytokinesis.

First, we define new concepts of Life Objects, Informative Objects and Virtual Objects, Discrete Chromosome Rings (DCR); we introduce a mathematical concept of meridian plane (MP) in a three dimensional (3-D) cylindrical coordinate system (CCS). Based on these concepts, classic mechanics, classic electromagnetism and published biological data, we develop our 3-D physical models of natural and normal mitosis (with asters) and cytokinesis, for animal cells in M phase. We propose following hypotheses: Chromosomes Exclusion: No normally and naturally replicated chromosomes can occupy the same nucleus without growing sizes of the nucleus and the cell. Spontaneous and strong electromagnetic fields (EMF) forces among chromosomes, centrosomes and microtubules split the nucleus and separate the two sets of sister chromatids when they are strong enough. Nuclei Exclusion: No normally and naturally doubled nuclei can occupy the same cell if the doubled size of nuclei is not far smaller than size of the cell. The spontaneous and strong EMF forces in protoplasm (or cortex), separate two sets of chromosomes, spindles and poles, drive contractile proteins to the equator in cell cortex, and continue to guide and to transport free charged objects until complete the cytokinesis. Centrioles Exclusion: No naturally and normally doubled centrioles can occupy the same centrosome. The spontaneous and strong repulsive EMF forces are the primary cause for the exclusions. The principles of our models are also applied to mitosis and cytokinesis for lower plant cells, to that of multiple nuclei or mutant chromosomes, and to meiosis, for both animal cells and lower plant cells.

Animals↗
PubMed2003

A three dimensional (3-D) physical model of ribosome movement in protein synthesis.

In this study, we propose new concepts of Active Potential Energy Well, Specificity and Non-Specificity of the wells. We perform these concepts to establish a 3-D physical model and to elucidate how a complete functional ribosome traps an aminoacyl tRNA, and how it moves along the mRNA template in the elongation of protein synthesis. In our model, we first introduce concepts of reduced mass and relative coordinates of a two objects system. Then we simplify a ribosome movement along mRNA in protein synthesis. We also introduce concepts of active objects and active controls in this study. Our model is based on quantum mechanics, thermal dynamics and the published biochemical data.

Cell Movement↗
PubMed2003

A three dimensional (3-D) physical model of DNA polymerase movement in DNA replication.

In this study, we propose new concepts of Active Potential Energy Well, Specificity and Non-Specificity of the wells. We perform these concepts to establish a 3-D physical model and to elucidate how a complete functional DNA polymerase traps a deoxyribonucleoside triphosphate, and how it moves along a DNA template strand in the elongation of a DNA replication. In our model, we first introduce concepts of reduced mass and relative coordinates of a two objects system. Then we simplify a DNA polymerase movement in DNA replication. We also introduce concepts of active objects and active controls in this study. Our model is based on quantum mechanics, thermal dynamics and published biochemical data.

Computer Simulation↗
PubMed2003

[Meta-analysis on the association of AGT M235T polymorphism and essential hypertension in Chinese population].

OBJECTIVE: To study on the association of M235T polymorphism of the angiotensinogen gene extron 2 (AGT/M235T) and essential hypertension (EH) in Chinese population by means of Meta-analysis. METHODS: Odds ratios (OR) of AGT M235T genotype distributions in EH patients against healthy controls were analyzed. All the relevant studies were identified, poor-qualified studies eliminated, and the risk of publication bias excluded. The Meta-analysis software, REVMAN4.1, was applied for investigating heterogeneity among individual studies and summarizing the effects across studies. RESULTS: A total of 853 cases and 835 controls from 10 studies were included. No heterogeneity among the studies was noticed. The frequencies of the AGT TT, MT and MM genotypes were 65%, 30%, and 4.9% in cases and 50.6%, 41.8% and 7.5% in controls respectively. The frequencies of the AGT T allele were 80% in cases and 72% in controls. The pooled OR (with 95% CI) of TT vs MT + MM was 1.76 (1.44 - 2.16) (P < 0.000 01) with T vs M 1.54 (1.31 - 1.81). The pooled OR of MM vs MT + TT was 0.67 (0.45 - 1.00) (P = 0.05). CONCLUSION: In Chinese population (mainly the Hans), TT genotype might be associated with the increased risk of EH while MM genotype be associated with low risk of EH.

Alleles↗
PubMed2002

2-Arylindoles as gonadotropin releasing hormone (GnRH) antagonists: optimization of the tryptamine side chain.

A series of 2-arylindoles containing novel heteroaromatic substituents on the tryptamine tether, based on compound 1, was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) antagonists. Successful modifications of 1 included chain length variation (reduction) and replacement of the pyridine with heteroaromatic groups. These alterations culminated in the discovery of compound 27kk which had excellent in vitro potency and oral efficacy in rodents.

Administration, Oral↗