Biomedical subjects

Ning Chen

Publications and source records attributed to Ning Chen.

At least 37 records · Page 2Linked to original sources

PubMed2005

Discovery of potent, orally available vanilloid receptor-1 antagonists. Structure-activity relationship of N-aryl cinnamides.

The vanilloid receptor-1 (TRPV1 or VR1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role in regulating the function of sensory nerves. A growing body of evidence demonstrates the therapeutic potential of TRPV1 modulators, particularly in the management of pain. As a result of our screening efforts, we identified (E)-3-(4-tert-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide (1), an antagonist that blocks the capsaicin-induced and pH-induced uptake of (45)Ca(2+) in TRPV1-expressing Chinese hamster ovary cells with IC(50) values of 17 +/- 5 and 150 +/- 80 nM, respectively. In this report, we describe the synthesis and structure-activity relationship of a series of N-aryl cinnamides, the most potent of which (49a and 49b) exhibit good oral bioavailability in rats (F(oral) = 39% and 17%, respectively).

Administration, Oral↗

PubMed2005

How does DNA compaction favor chiral selectivity with cationic species? Higher selectivity with lower cationic charge.

A single-molecule study on giant DNA compaction by enantiomeric dications and tetracations demonstrates that strong chiral discrimination in DNA compaction is manifested only if the positive charge on enantiomeric multications is relatively low. The increase in cationicity of the chiral compaction agent inevitably leads to an increase in nonspecific electrostatic interactions and quenching of chiral discrimination in the DNA-folding phase transition.

Bacteriophage T4↗

PubMed2005

Novel mutations and polymorphisms in genes causing hereditary hemorrhagic telangiectasia.

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder caused by mutations in Endoglin (ENG) or activin receptor-like kinase-1 (ALK1, ACVRL1) genes. We performed molecular characterization in clinically affected probands of 31 HHT families and detected a total of 28 different mutations in the two genes, including four shared by more than one family. Twelve mutations were identified in the ENG gene, six of which were novel and comprised two nonsense mutations in exons 6 and 8, deletions in exons 5 and 11, and splice site mutations in exon 12 and intron 8. Eleven of sixteen mutations identified in the ALK1 gene were novel single base pair substitutions in exons 4, 7, 8, and 9. We also describe the first de novo ALK1 mutation that causes a previously unreported c.1133C>A substitution of a highly conserved residue (p.P378H). The proband and his two daughters, who also carried the familial mutation, all suffered from gastrointestinal (GI) bleeding. In addition, we report seven newly identified polymorphisms and summarize all known ones in both genes.

Activin Receptors, Type II↗

PubMed2005

Reproductive aging results in a reconfigured ovarian antioxidant defense profile in rats.

OBJECTIVE: To test our hypothesis that reproductive aging changes the ovarian oxidative stress defense profile, in response to prostaglandin F2alpha (PGF2alpha) during corpus luteum regression, because how a cell or an organ handles reactive oxygen intermediates may be dependent on the biological age of the organism. DESIGN: Animal experimentation using rat model of corpus luteum regression. SETTING: University reproductive biology laboratory. ANIMAL(S): Control (26-day-old) and 8- to 9-month-old (reproductive aging) rats. INTERVENTION(S): Corpus luteum formation was induced in control and 8- to 9-month-old (reproductive aging) rats with pregnant mare serum gonadotropin followed by human chorionic gonadotropin. Regression was then initiated with PGF2alpha. MAIN OUTCOME MEASURE(S): Vitamin E, glutathione reductase, glutathione peroxidase, catalase, and thiobarbituric acid-reacting substances were measured. RESULT(S): Ovaries from reproductive aging rats, compared with the control (26-day-old) group, had elevated vitamin E levels at 0, 2, and 24 hours after PGF2alpha. At 2 and 24 hours after PGF2alpha, the aging ovaries had lower glutathione reductase levels. CONCLUSION(S): These data suggest that the reproductive aging ovary has a transformed oxidative stress defense profile and that this may account for some of the physiological changes found in reproductive aging.

Aging↗

PubMed2005

Characterization of a mutant Listeria monocytogenes strain expressing green fluorescent protein.

To construct a recombinant strain of Listeria monocytogenes for the expression of heterologous genes, homologous recombination was utilized for insertional mutation, targeting its listeriolysin O gene (hly). The gene encoding green fluorescent protein (GFP) was used as the indicator of heterologous gene expression. The gene gfp was inserted into hly downstream from its promoter and signal sequence by an overlapping extension polymerase chain reaction, and was then cloned into the shuttle plasmid pKSV7 for allelic exchange with the L. monocytogenes chromosome. Homologous recombination was achieved by growing the electro-transformed L. monocytogenes cells on chloramphenicol plates at a non-permissive temperature. Sequencing analysis indicated correct insertion of the target gene in-frame with the signal sequence. The recombinant strain expressed GFP constitutively as revealed by fluorescence microscopy. The mutant strain L. monocytogenes hly-gfp lost its hemolytic activity as visualized on the blood agar or when analyzed with the culture supernatant samples. Such insertional mutation resulted in a reduced virulence of about 2 logs less than its parent strain L. monocytogenes 10403s as shown by the 50%-lethal-dose assays in the mouse and embryonated chicken egg models. These results thus demonstrate that mutated L. monocytogenes could be a potential carrier for the expression of heterologous passenger genes or could act as an indicator organism in the food industry.

Alleles↗

PubMed2005

Transcriptional profile of NeuroD expression in a human fetal astroglial cell line.

NeuroD1, a member of the basic helix-loop-helix (bHLH) protein family, is a transcription factor that plays a pivotal role in terminal differentiation of neural progenitors. The primary objective was to generate an early transcriptional profile triggered by NeuroD1 to guide future studies on mechanisms of neuronal differentiation. The human NeuroD1 coding region was amplified from human fetal brain RNA using specific primers and cloned into a CMV expression vector (CT-GFP-TOPO/pcDNA3.1). Transfection of a fetal glial cell line with this construct resulted in expression of NeuroD1 in 13-15% of the cells. Markers typical of early neuronal development were observed by immunocytochemical staining in a small proportion of transfected cells. To enrich the population of NeuroD1-expressing cells, fluorescence-activated cell sorting (FACS) was used to purify and collect the NeuroD1/GFP+ cells. Total RNA was extracted from the pair of cultures (NeuroD1/GFP vs. control plasmid/GFP) and processed for gene expression studies. A final gene list was composed from those probe sets that were either increased or decreased in the NeuroD1-expressing cells in three independent experiments (p < 0.001). Each gene was investigated further for possible roles in neurogenesis and a subset of 177 genes was chosen based on the following characteristics: a) genes that are potential NeuroD1 dimerization partners, b) genes that modulate other bHLH transcription factors, c) genes related to development, and d) genes associated with neural induction, outgrowth, and terminal differentiation. DNA microarray analysis of NeuroD1 expression in an astroglial cell line produced a "snapshot" transcriptional profile that will be useful in deciphering the complex molecular code that specifies a neuronal fate.

Astrocytes↗

PubMed2004

The lateral signal for LIN-12/Notch in C. elegans vulval development comprises redundant secreted and transmembrane DSL proteins.

The vulval precursor cells (VPCs) are spatially patterned by a LET-23/EGF receptor-mediated inductive signal and a LIN-12/Notch-mediated lateral signal. The lateral signal has eluded identification, so the mechanism by which lateral signaling is activated has not been known. Here, we computationally identify ten genes that encode potential ligands for LIN-12, and show that three of these genes, apx-1, dsl-1, and lag-2, are functionally redundant components of the lateral signal. We also show that transcription of all three genes is initiated or upregulated in VPCs in response to inductive signaling, suggesting that direct transcriptional control of the lateral signal by the inductive signal is part of the mechanism by which these cell signaling events are coordinated. In addition, we show that DSL-1, which lacks a predicted transmembrane domain, is a natural secreted ligand and can substitute for the transmembrane ligand LAG-2 in different functional assays.

Animals↗

PubMed2004

Study on shift schedule saving energy of automatic transmission of ground vehicles.

To improve ground vehicle efficiency, shift schedule energy saving was proposed for the ground vehicle automatic transmission by studying the function of the torque converter and transmission in the vehicular drivetrain. The shift schedule can keep the torque converter working in the high efficiency range under all the working conditions except in the low efficiency range on the left when the transmission worked at the lowest shift, and in the low efficiency range on the right when the transmission worked at the highest shift. The shift quality key factors were analysed. The automatic trans-mission's bench-test adopting this shift schedule was made on the automatic transmission's test-bed. The experimental results showed that the shift schedule was correct and that the shift quality was controllable.

Algorithms↗

PubMed2004

Chemical modification of glycerinated stalks shows tyrosine residues essential for spasmoneme contraction of Vorticella sp.

Chemical modification of glycerinated stalks of Vorticella with TNM is used to investigate the role of tyrosine residues in the Ca(2+)-induced contraction of the spasmoneme. Tetranitromethane (TNM) is often employed as a specific reagent for the nitration of tyrosine residues in a protein at neutral and slightly alkaline pHs although TNM can also oxidize cysteine residues in the acidic and neutral pH range. Prior incubation with Ca(2+) of stalks to be treated with TNM can protect the spasmoneme from irreversible denaturation. On the other hand, TNM treatment in the absence of free Ca(2+) causes an irreversible denaturation of the spasmoneme. It was revealed by us that an isolated Ca(2+)-binding protein called spasmin could not bind with Ca(2+) after TNM treatment, even if the treatment was performed in the presence of Ca(2+). In an additional experiment, we confirmed that the chemical modification of cysteine residues in the spasmoneme with N-7-dimethyl-amino-4methyl- coumarinyl- maleimide (DACM) has no effect on the contractibility. These results suggest that tyrosine residues in spasmin are essential for spasmoneme contraction and are protected from TNM in the presence of Ca(2+) when spasmin binds with its receptor protein in the spasmoneme.

Animal Structures↗

PubMed2004

[Sputum analysis in patients with "disharmony of stomach"].

OBJECTIVE: To analyze the amount and inflammatory components of the sputum in patients with "disharmony of stomach", including gastroesophageal reflux disease, peptic ulcer and chronic gastritis. METHODS: Sputum production was induced by inspiration of aerosol of 3.5% hypertonic saline with ultrasonic nebulizer, and the total cell count in the sputum was examined. Sputum smear stained with Gimsa was used in differential counting under light microscope. Bacterial culture in the sputum was performed in the usual way. Peak expiratory flow (PEF) was tested to study the airway responsiveness. RESULTS: The amount of sputum, the total cells and eosinophils in the sputum of the patients with "disharmony of stomach" were higher than those of the control. PEF decreased following sputum induction. These parameters returned to control level after treatment with Chinese herbs. Bacterial culture was negative. CONCLUSION: "Disharmony of stomach" can cause the bronchial inflammation (non-infection) characterized by eosinophil increase.

Adult↗

PubMed2004

[One stage urethroplasty by using bladder mucosa for treatment of hypospadias].

OBJECTIVE: To investigate the safety, efficacy and morbidity of one stage urethroplasty by using bladder mucosa for treatment of hypospadias. METHODS: From August 1991 to August 2003, 38 cases of congenital hypospadias were given bladder mucosa flap procedure and one stage urethroplasty. RESULTS: Thirty-eight cases of hypospadias treated with one stage urethroplasty by using bladder mucosa were followed up 6 months-9 years after the procedure. The success rate of the operation was 95%. Three cases of urethral fistula after the procedure were surgically repaired again, 2 cases of urethral stricture recovered after distension. The complication markedly lessened, micturation became normal with the reconstructed meatus situated at the proper site on the glands. CONCLUSION: One stage urethroplasty by using bladder mucosa for treatment of hypospadias is a simple, effective and safe surgery.

Adolescent↗

PubMed2004

Minimal 16q genomic loss implicates cadherin-11 in retinoblastoma.

Retinoblastoma is initiated by loss of both RB1 alleles. Previous studies have shown that retinoblastoma tumors also show further genomic gains and losses. We now define a 2.62 Mbp minimal region of genomic loss of chromosome 16q22, which is likely to contain tumor suppressor gene(s), in 76 retinoblastoma tumors, using loss of heterozygosity (30 of 76 tumors) and quantitative multiplex PCR (71 of 76 tumors). The sequence-tagged site WI-5835 within intron 2 of the cadherin-11 (CDH11) gene showed the highest frequency of loss (54%, 22 of 41 samples tested). A second hotspot for loss (39%, 9 of 23 samples tested) was detected within intron 2 of the cadherin-13 (CDH13) gene. Furthermore, deletion of the exons of CDH11 and/or WI-5835 was shown by quantitative multiplex PCR in 17 of 30 (57%) of previously untested tumors. Immunoblot analyses revealed that 91% (20 of 22) retinoblastoma exhibited either a complete loss or a decrease of the intact form of CDH11 and 8 of 13 showed a prevalent band suggestive of the variant form. Copy number of WI-5835 for these samples correlated with CDH11 protein expression. CDH11 staining was evident in the inner nuclear layer in early mouse retinal development and in small transgenic murine SV40 large T antigen-induced retinoblastoma tumors, but advanced tumors frequently showed loss of CDH11 expression by reverse transcription-PCR, suggestive of a role for CDH11 in tumor progression or metastasis. CDH13 protein and mRNA were consistently expressed in all human and murine retinoblastoma compared with normal adult human retina. Our analyses implicate CDH11, but not CDH13, as a potential tumor suppressor gene in retinoblastoma.

Animals↗

PubMed2004

[Experimental study of the fungiform papilla and taste bud regeneration following microsurgical repair of lingual nerve in rat].

PURPOSE: To investigate the changes of taste buds following injury to lingual nerve and the regeneration of the fungiform papillae and taste buds following microsurgical epineurial anastomosis of transecting injured lingual nerves in rats. METHODS: We observed the numbers and shapes of the fungiform papillae and taste buds with stereomicroscope, light microscope, and scanning electron microscope at 20 and 100 days after the clamp injury to lingual nerve, or the transecting injury to lingual nerve with/without immediate microsurgical epineurial anastomosis of the injured lingual nerve in rats. RESULTS: The fungiform papillae and taste buds degenerated, atrophied and their numbers diminished obviously at 20 days following either the clamp injury or transecting injury to the lingual nerve. The fungiform papillae and taste buds didn't regenerate spontaneously at 100 days following transection of the lingual nerve without microsurgery. The degenerated fungiform papillae and taste buds regenerated and recovered completely at 100 days following both clamp injury to the lingual nerve and transection of the lingual nerve with immediate microsurgical epineurial anastomosis. CONCLUSION: The degenerated fungiform papillae and taste buds have good ability to regenerate spontaneously following clamp injury to the lingual nerve; the degenerated fungiform papillae and taste buds can regenerate completely with immediate microsurgical epineurial anastomosis of the transected lingual nerve. The quantity and morphology of fungiform papillae and taste buds can be used as objective indicators in the function rehabilitation of injured lingual nerve.

Animals↗

PubMed2004

[Changes of taste bud and fungiform papillae after 60Co radiation in rat].

OBJECTIVE: To observe the morphological changes and the regenerating ability of the fungiform papillae and taste buds after 60Co radiation with clinical doses in rats. METHODS: The heads, faces and necks of 30 SD rats were radiated with a large dose and one time of 60Co in the clinical radiation. The general living condition and the number and shape of the fungiform papillae and taste buds of the tongues were observed after the radiation in rats. RESULTS: In the group of 60Co radiation, the animals had wilting, decreasing appetite, losing weight. The heads, faces and necks of animals appeared redness, peeling of hair, increasing of secretions in 5 days after the 60Co radiation. The changes reached the summit in 10 days and the general living condition of the animals recovered in 60 days. The fungiform papillae and taste buds of the animals appeared degeneration, atrophy and collapsing in 5 days after the 60Co radiation. The injuries reached the summit in 10-20 days and the fungiform papillae and taste buds regenerated partially, and the some atrophied fungiform papillae and taste buds were not regenerated in 60 days. CONCLUSION: The damage to fungiform papillae and taste buds of tongue following the 60Co radiation with the clinical doses was very serious. The damaged fungiform papillae and taste buds can regenerate partially, but not completely.

Animals↗

PubMed2004

[Clinical observation of xuesaitong injection on the treatment of chronic respiratory failure].

OBJECTIVE: To observe the effect of Xuesaitong Injection on the treatment of chronic respiratory failure. METHODS: 86 cases were classified into two groups randomly. The control group was given routine therapy with western medicine. Based on the regime, the test group received Xuesaitong injection, i.v., once a day. Therapeutic course was 14 days in every patient. RESULTS: The overall effective rate (81.3%) of test group was higher than that of control group (P < 0.05). The indexes of the test group related to blood gas analysis and blood rheology were significantly improved in comparison with the control group. CONCLUSION: Xuesaitong Injection has an apparent effect on chronic respiratory failure.

Aged↗

PubMed2003

[Transmaxillary approach for micro resection of clivus tumors, clinical analysis of 16 cases].

OBJECTIVE: To investigate the indications, key point, advantages, and disadvantages of transmaxillary approach for microsurgical removal of clivus tumors. METHODS: The clinical data of 16 consecutive patients with clivus tumors operated upon through transmaxillary approach, based on Le Fort I ostectomy, July 1999 to May 2002 were retrospectively reviewed. RESULTS: Of the 16 patients, 8 patients suffered from chordoma, 2 from angiofibroma, 1 from pituitary adenoma, 1 from chondroma, 1 from adenocarcinoma of grade II, 1 from mucoid cyst, 1 from myeloma, and 1 from fibrous dysplasia of bone. Four out of the 16 cases were with recurrent tumors after operation performed in other hospitals. The operation field of all 16 patients was satisfactorily exposed. The tumors of 10 cases were totally removed under microscope, and 6 tumors were subtotally removed. The complications included rhinorrhea in 1 case and malocclusion in 3 cases. There was no operative mortality. All patients were followed up for 6 approximately 40 months (ion average 20 months) with MRI. Four of them had local recurrence within 1 year, 1.5 years, 2 years, and 9 months respectively after operational and have lived with tumors till now. The remainders had resumed their normal life. CONCLUSION: An ideal approach, transmaxillary approach facilitates the resection of clivus tumors, with satisfying exposure and fewer complications.

Adenoma↗

PubMed2003

Ascorbic acid induces a marked conformational change in long duplex DNA.

Ascorbic acid is often regarded as an antioxidant in vivo, where it protects against cancer by scavenging DNA-damaging reactive oxygen species. However, the detailed mechanism of the action of ascorbic acid on genetic DNA is still unclear. We examined the effect of ascorbic acid on the higher-order structure of DNA through real-time observation by fluorescence microscopy. We found that ascorbic acid generates a pearling structure in single giant DNA molecules, with elongated and compact regions coexisting along a molecular chain. Results from electron microscopy and atomic force microscopy indicate that the compact regions assume a loosely packed conformation. A possible mechanism for the induction of this conformational change is discussed in relation to the interplay between the higher-order and second-order structures of DNA.

Ascorbic Acid↗

PubMed2003

Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation.

Amyotrophic lateral sclerosis (ALS), a multifactorial disease characterized by diffuse motor neuron degeneration, has proven to be a difficult target for stem cell therapy. The primary aim of this study was to determine the long-term effects of intravenous mononuclear human umbilical cord blood cells on disease progression in a well-defined mouse model of ALS. In addition, we rigorously examined the distribution of transplanted cells inside and outside the central nervous system (CNS), migration of transplanted cells to degenerating areas in the brain and spinal cord, and their immunophenotype. Human umbilical cord blood (hUCB) cells (10(6)) were delivered intravenously into presymptomatic G93A mice. The major findings in our study were that cord blood transfusion into the systemic circulation of G93A mice delayed disease progression at least 2-3 weeks and increased lifespan of diseased mice. In addition, transplanted cells survived 10-12 weeks after infusion while they entered regions of motor neuron degeneration in the brain and spinal cord. There, the cells migrated into the parenchyma of the brain and spinal cord and expressed neural markers [Nestin, III Beta-Tubulin (TuJ1), and glial fibrillary acidic protein (GFAP)]. Infused cord blood cells were also widely distributed in peripheral organs, mainly the spleen. Transplanted cells also were recovered in the peripheral circulation, possibly providing an additional cell supply. Our results indicate that cord blood may have therapeutic potential in this noninvasive cell-based treatment of ALS by providing cell replacement and protection of motor neurons. Replacement of damaged neurons by progeny of cord blood stem cells is probably not the only mechanism by which hUCB exert their effect, since low numbers of cells expressed neural antigens. Most likely, cord blood efficacy is partially due to neuroprotection by modulation of the autoimmune process.

Alanine↗