Biomedical subjects

Ming Li

Publications and source records attributed to Ming Li.

At least 37 records · Page 2Linked to original sources

PubMed2008

Escitalopram in major depressive disorder: a multicenter, randomized, double-blind, fixed-dose, parallel trial in a Chinese population.

Escitalopram, the S-enantiomer of citalopram and the most selective of the selective serotonin reuptake inhibitor (SSRI) has been shown to be efficacious in the treatment of major depression in white populations. Our aim in this study was to investigate the efficacy and tolerability of escitalopram in Chinese patients with moderate to severe major depression. Patients who met DSM-IV criteria for a major depressive episode were enrolled in this multicenter, randomized, double-blind, fixed-dose comparison trial. Patients were given escitalopram 10 mg/day or fluoxetine 20 mg/day for 8 weeks. All patients were assessed with the 17-item Hamilton Depression Rating Scale (HAM-D-17) and the Montgomery-Asberg Depression Rating Scale (MADRS). Tolerability was assessed on the basis of adverse effects (measured with a locally developed checklist), regular biochemical tests, and electrocardiograph (ECG) assessments. Two hundred forty patients were enrolled and randomized to escitalopram (123 patients) or fluoxetine (117 patients). The HAM-D-17 total scores of both groups decreased significantly from baseline, but there was no significant difference at week 8 between the two groups (15.8 for escitalopram and 14.7 for fluoxetine; P >.05). There were no significant differences in response rates at all visits after treatment based on either HAM-D-17 or MADRS. A post hoc analysis indicated that escitalopram was superior to fluoxetine on two items of the HAM-D-17: "depressed mood" (P =.023) and "work and interest" (P =.024). The adverse events reported in the escitalopram and fluoxetine groups were comparable, and most were mild to moderate. Both drugs showed good compliance profiles. Escitalopram 10 mg/day is at least as efficacious as fluoxetine 20 mg/day and well tolerated in Chinese patients with major depression, with possible superiority in some core symptoms such as "depressed mood" and "work and interest."

Adolescent↗

PubMed2007

Novel pycnodysostosis mouse model uncovers cathepsin K function as a potential regulator of osteoclast apoptosis and senescence.

Pycnodysostosis is a genetic bone disease featuring the unique bone homeostasis disorders of osteolysis and osteopetrosis in the same organism. The pathomechanism for pycnodysostosis has been largely unknown due to the unavailability of a pycnodysostosis mouse model with all the traits of the disease. We generated cathepsin K(-/-) mouse strains in the 129/Sv and C57BL/6J backgrounds and found that, only in the 129/Sv background, cathepsin K(-/-) mice exhibit many characteristics of the human pycnodysostosis-like phenotype. Our data indicated that 129/Sv cathepsin K(-/-) osteoclasts (OCs) lacked normal apoptosis and senescence and exhibited over-growth both in vitro and in vivo. These abnormalities resulted in an unusually high OC number, which is consistent with a recent case study of human pycnodysostosis. Our results show that cathepsin K function has different effects around the skeleton due to site-specific variations in bone homeostasis, such as phenotypes of osteopetrosis in tibiae and osteolysis in calvariae as a result of cathepsin K mutation. Our data demonstrated that the expression levels of p19, p53 and p21 were significantly reduced in 129/Sv cathepsin K(-/-) OCs and forced expression of cathepsin K in pre-OCs induced premature senescence and increased expression of p19, p53 and p21. This is the first evidence that cathepsin K plays a key role in OC apoptosis and senescence, revealing the importance of OC senescence in bone homeostasis. The finding of this novel cathepsin K function provides insight into the pathomechanism of pycnodysostosis and may provide new drug targets for diseases involved in OC-related abnormal bone homeostasis.

Animals↗

PubMed2007

Somatosensory cortical plasticity in carpal tunnel syndrome treated by acupuncture.

Carpal tunnel syndrome (CTS) is a common entrapment neuropathy of the median nerve characterized by paresthesias and pain in the first through fourth digits. We hypothesize that aberrant afferent input from CTS will lead to maladaptive cortical plasticity, which may be corrected by appropriate therapy. Functional MRI (fMRI) scanning and clinical testing was performed on CTS patients at baseline and after 5 weeks of acupuncture treatment. As a control, healthy adults were also tested 5 weeks apart. During fMRI, sensory stimulation was performed for median nerve innervated digit 2 (D2) and digit 3 (D3), and ulnar nerve innervated digit 5 (D5). Surface-based and region of interest (ROI)-based analyses demonstrated that while the extent of fMRI activity in contralateral Brodmann Area 1 (BA 1) and BA 4 was increased in CTS compared to healthy adults, after acupuncture there was a significant decrease in contralateral BA 1 (P < 0.005) and BA 4 (P < 0.05) activity during D3 sensory stimulation. Healthy adults demonstrated no significant test-retest differences for any digit tested. While D3/D2 separation was contracted or blurred in CTS patients compared to healthy adults, the D2 SI representation shifted laterally after acupuncture treatment, leading to increased D3/D2 separation. Increasing D3/D2 separation correlated with decreasing paresthesias in CTS patients (P < 0.05). As CTS-induced paresthesias constitute diffuse, synchronized, multidigit symptomatology, our results for maladaptive change and correction are consistent with Hebbian plasticity mechanisms. Acupuncture, a somatosensory conditioning stimulus, shows promise in inducing beneficial cortical plasticity manifested by more focused digital representations.

Acupuncture Therapy↗

PubMed2007

Cyclin I and p53 are differentially expressed during the terminal differentiation of the postnatal mouse heart.

In this study, we have used Ki-67 and MF20 mAb to determine how extensively cardiomyocytes proliferate in the postnatal mouse heart. It was established that the cardiomyocytes divided rapidly in 2-day-old hearts. However, at 13 days, the majority of cardiomyocytes had entered into terminal growth arrest and differentiation. We exploited this finding in order to identify proteins that were associated with cardiomyocyte growth and differentiation. The protein profiles of 2- and 13-day-old hearts were established by two-dimensional electrophoresis and compared. Seventeen protein spots were found to be differentially expressed at day 13. Eight of them were up-regulated while the remaining nine protein spots were down-regulated. We focused our attention on 2 of the proteins identified by MALDI-TOF MS, cyclin I and p53, because they are both believed to be involved in cell cycle regulation. Western blot analysis confirmed that both proteins were positively up-regulated in the 13-day-old postnatal heart. To determine directly whether these proteins were associated with cell proliferation, we examined their expression patterns in H9c2 cardiomyocytes maintained in vitro. We established that cyclin I expression was low during the growing phase of H9c2 culture and high during the growth arrest/differentiation phases. In contrast, p53 expression was unchanged during both phases. The various growth phases were confirmed by the presence of cyclin A and growth arrest-specific 1 proteins. We investigated whether silencing cyclin I expression using cyclin I-siRNA could promote an increase in H9c2 cell proliferation. It was determined that silencing cyclin I could enhance a small, but significant, increase in H9c2 cell division. Similar results were obtained for cardiomyocytes extracted from 13-day-old hearts. These results imply that the reason why cardiomyocytes in 13-day-old hearts increased cyclin I expression was probably associated with terminal growth arrest. However, the increase in p53 expression was probably associated with cardiomyocyte differentiation, rather than growth arrest.

Animals↗

PubMed2006

Identification of a key functional region in harpins from Xanthomonas that suppresses protein aggregation and mediates harpin expression in E. coli.

In the current study, we identified a key functional region in harpins from Xanthomonas that suppressed protein aggregation and mediated its expression in E. coli. Our data suggested that the presence of two common features in harpins [Wei et al. (1992) Science 257:85-88], namely, high glycine content and lack of cysteine residues, were not sufficient for Xanthomonas to elicit hypersensitive response (HR) activity or heat stability. Additionally, bioinformatic analyses revealed that the secondary structure of a conserved N-terminal region consisting of 12 highly hydrophilic amino acids (QGISEKQLDQLL) was alpha-helical. Following site-directed mutagenesis deletion of this region, the three mutated harpin proteins, in cultures induced at 37 degrees C, failed to elicit a HR in tobacco leaves. However, at 24 degrees C, two mutated harpins retained the ability to elicit HR, albeit with lower expression levels than that noted with the wild-type. SDS-PAGE and Western blot data suggested the HpaG mutant protein was found almost entirely in the inclusion body. These data demonstrated that these conserved amino acid residues played a critical role in protein aggregation and inclusion body formation in harpins from Xanthomonas.

Amino Acid Sequence↗

PubMed2006

Preliminary structural studies of the transcriptional regulator CmeR from Campylobacter jejuni.

In Campylobacter jejuni, a gram-negative bacterial pathogen causing gastroenteritis in humans, the CmeR regulatory protein controls transcription of the multidrug transporter gene operon cmeABC. CmeR belongs to the TetR family of transcriptional regulators. The 210-residue CmeR consists of two functional motifs: an N-terminal DNA-binding domain and a C-terminal ligand-binding domain. It is predicted that the DNA-binding domain interacts directly with target promoters, while the C-terminal motif interacts with inducing ligands (such as bile salts). As an initial step towards confirming this structural model, recombinant CmeR protein containing a 6 x His tag at the N-terminus was crystallized. Crystals of ligand-free CmeR belonged to space group P2(1)2(1)2, with unit-cell parameters a = 37.4, b = 57.6, c = 93.3 A. Diffraction was observed to at least 2.2 A at 100 K. Analysis of the detailed CmeR structure is currently in progress.

Campylobacter jejuni↗

PubMed2006

Expression and secretion of immunoglobulin alpha heavy chain with diverse VDJ recombinations by human epithelial cancer cells.

Generally, only B lymphocytes express immunoglobulin. Recently, we found the expression of Ig alpha heavy chain in human epithelial cancer cells unexpectedly. We first detected Ig VDJ-Calpha and Ialpha-Calpha transcripts in multiple cancer cell lines. Further, the configuration of the Ig heavy chain genomic locus was analyzed in human cancer cells. We found that cancer cells have the recombination VDJ region, but bear Ig Salpha region in germline configuration, which is different from Ig expression pattern in B cells. And human epithelial cancers possess the essential effectors including RAG-1 and RAG-2, but not activation induced cytidine deaminase (AID) protein. These provide further proofs for Ig alpha expression. In addition, we found that human cancer cells not only express the protein of Ig alpha chain, but also secrete the protein in secretory IgA (SIgA) pattern. Importantly, diverse CDR3 recombinations were found in human cancer cells of different epithelial origin. Since IgA is the key immunoglobulin which contributes to local immunity of mucous membrane, the aberrant expression of Ig alpha heavy chain might increase our further comprehension to development and immunity of cancers.

Base Sequence↗

PubMed2006

Effect of clopidogrel on the inflammatory progression of early atherosclerosis in rabbits model.

Atherosclerosis is an inflammatory response of the arterial wall to 'injury', which is prominently driven by inflammatory factors. Clopidogrel reduces early atherosclerosis, however, the role of clopidogrel in modulating inflammatory progression of atherosclerosis is less investigated. We wished to determine the effect of clopidogrel on progression of established atherosclerosis, vascular inflammatory factors and compared with that of aspirin and atorvastatin. Fifty male New Zealand white (NZW) rabbits were divided into five groups randomly including negative group. The rabbits were fed with a normal diet or a high cholesterol diet for 7 weeks. The right iliac artery of animals except negative group were balloon injured 1 week after initiation of the diet, then animals were treated with clopidogrel (4 mg/kg/day), aspirin (12 mg/kg/day), atorvastatin (2.5mg/kg/day) or placebo for 6 weeks. At the end of the study, the placebo (positive) group had significant progression of atherosclerosis compared with negative group. In contrast, clopidogrel, aspirin or atorvastatin treated rabbits showed a significant reduction in progression of atherosclerosis and decreased the levels of P-selection, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) in serum and vascular wall. Among three drugs, the action of clopidogrel is the most powerful in decreasing the levels of inflammatory factors. These results suggest that in a rabbit atherosclerosis model, clopidogrel retards the progression of established lesions and that this effect is paralleled by a suppression of inflammatory factors.

Animals↗

PubMed2006

Higher-order incidence transfer matrix method used in three-dimensional photonic crystal coupled-resonator array simulation.

The plane-wave-based transfer matrix method with rational function interpolation and higher-order plane-wave incidence is proposed as an efficient calculation approach to simulate three-dimensional photonic crystal devices. As an example, the dispersion relations and quality factors are calculated for resonant cavity arrays embedded in a woodpile photonic crystal. An interesting ultraslow negative group velocity is observed in this structure.

Journal Article↗

PubMed2006

Compaction dynamics of single DNA molecules under tension.

Using transverse magnetic tweezers, we studied the dynamics of DNA compaction induced by hexaammine cobalt chloride under constant forces. Discontinuous DNA compaction events were found for forces ranging from 0.5 to 1.7 pN, with approximately 270 nm DNA adsorbed in each compaction event. Forces larger than 6 pN were found able to unravel the toroid in a similar intermittent stepwise manner. The observations indicate that the folding/unfolding events are transitions between two metastable structural states which are separated by a tension-dependent energy barrier. Analysis of the waiting time revealed that the degree of the package ordering of DNA in a toroid depends on the compaction kinetics.

Bacteriophage lambda↗

PubMed2006

The dual actions of angiogenesis and anti-apoptosis induced by an isolated fraction from Geum japonicum repair muscle ischemia.

The fundamental improvement of muscle ischemia requires the re-establishment of sufficient vessel network. Despite many kinds of drugs have been used for ischemia, effective angiogenic drug is very limited. Here, we reported the identification and isolation of a potent angiogenic fraction (angio-T) from Geum japonicum and assessment of its therapeutic effects on muscle ischemia by reconstituting the insufficient blood supply network and enhancing cell survival potential. It was demonstrated that angio-T not only significantly enhanced the proliferation of cultured HCAECs in vitro, but also significantly enhanced the survival potential of the myofibers at risk and neovascularization in ischemic muscles leading to reconstitution of these vessel networks, significant reduction of ischemic areas, and significant myofiber regeneration in ischemic area one week post-ischemia.

Animals↗

PubMed2006

Redescription of Trypanosoma siniperca Chang 1964 from freshwater fish of China based on morphological and molecular data.

During the parasite fauna investigation within 2005, the freshwater fish trypanosome Trypanosoma siniperca Chang 1964 was isolated from the blood of Mandarin carp (Siniperca chuatsi) from Niushan Lake, Hubei Province, central China. Blood trypomastigotes were observed only, and the density of infection was low. Light microscopy examinations of this material made it possible to study in detail the morphology of this parasite and redescribe it according to current standards. T. siniperca is characterized also on the molecular level using the sequences of SSU rRNA gene. Phylogenetic analyses based on these sequences allowed clearer phylogenetic relationships to be established with other fish trypanosomes sequenced to date.

Animals↗

PubMed2006

Reconstitution of protein targeting to the inner envelope membrane of chloroplasts.

The chloroplast envelope plays critical roles in the synthesis and regulated transport of key metabolites, including intermediates in photosynthesis and lipid metabolism. Despite this importance, the biogenesis of the envelope membranes has not been investigated in detail. To identify the determinants of protein targeting to the inner envelope membrane (IM), we investigated the targeting of the nucleus-encoded integral IM protein, atTic40. We found that pre-atTic40 is imported into chloroplasts and processed to an intermediate size (int-atTic40) before insertion into the IM. Int-atTic40 is soluble and inserts into the IM from the internal stromal compartment. We also show that atTic40 and a second IM protein, atTic110, can target and insert into isolated IM vesicles in vitro. Collectively, our experiments are consistent with a "postimport" mechanism in which the IM proteins are first imported from the cytoplasm and subsequently inserted into the IM from the stroma.

Arabidopsis↗

PubMed2006

Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of the regulator AcrR from Escherichia coli.

This paper describes the cloning, expression, purification and preliminary X-ray data analysis of the AcrR regulatory protein. The Escherichia coli AcrR is a member of the TetR family of transcriptional regulators. It regulates the expression of the AcrAB multidrug transporter. Recombinant AcrR with a 6xHis tag at the C-terminus was expressed in E. coli and purified by metal-affinity chromatography. The protein was crystallized using hanging-drop vapor diffusion. X-ray diffraction data were collected from cryocooled crystals at a synchrotron light source. The best crystal diffracted to 2.5 A. The space group was determined to be P3(2), with unit-cell parameters a = b = 46.61, c = 166.16 A.

Base Sequence↗

PubMed2006

[Evaluation of the four simple methods in the diagnosis of diabetic peripheral neuropathy].

OBJECTIVE: To evaluate the efficacy of neuropathy symptom score/neuropathy disability score (NSS/NDS), Michigan Neuropathy Screening Instrument (MNSI), vibration perception threshold (VPT) and 24010 g monofilament examination in the diagnosis of diabetic peripheral neuropathy (DPN). METHODS: 240 patients with type 2 diabetes underwent the 4 simple tests: NSS/NDS, MNSI, VPT, and 10 g monofilament examination and nerve conduction velocity (NCV) examination. Using the results of NCV as golden criteria, the sensitivity, specificity, positive and negative predictive values, accuracy and kappa values of these tests were analyzed. RESULTS: The sensitivity, specificity, accuracy, and kappa value of MNSI score over 2 were 78.15%, 88.43%, 83.33%, and 0.67 respectively. The validity could be ranked in the following order with respect to the diagnosis of DPN: MNSI > VPT > NSS/NDS > 10 g monofilament examination. CONCLUSION: MNSI is a rapid, simple and reliable test for screening DPN in both diabetes clinics and epidemiological surveys.

Adult↗

PubMed2006

[Characteristics of dysfunction of islet beta-cell in newly diagnosed type 2 diabetic patients].

OBJECTIVE: To investigate the characteristics of the dysfunction of islet beta-cell in newly diagnosed type 2 diabetic patients. METHODS: Intravenous glucose tolerance test (IVGTT) was carried out on 352 newly diagnosed type 2 diabetic patients and 48 subjects with normal glucose tolerance (NGT) and then blood samples were collected 1, 2, 4, 6, and 10 minutes later to measure the plasma glucose and insulin to calculate the acute insulin response (AIR) and the area under the curve of insulin (AUC of insulin), homeostasis model assessment beta-cell (Homabeta), and Homa IR (insulin resistance). RESULTS: The median AIR of the type 2 diabetic patients was -33.7 pmol/L, significantly lower than that of the NGT subjects (6962.0 pmol/L, P < 0.001). The median AUC of the type 2 diabetic patients was 834.2 pmol/L, significantly lower than that of the NGT subjects (7934.7 pmol/L, P < 0.001). When the fasting plasma glucose (FPG) of the type 2 diabetic patients was above 7.0 mmol/L, the AIR value was remarkably reduced with a median level of 317.3 pmol/L, and then subsequently disappeared when the FPG was above 9.0 mmol/L. After adjustment of the insulin resistance assessed by HOMA IR, the Homabeta of the type 2 diabetic patients was reduced to be 30% that of the NGT subjects (3.7 +/- 0.9 vs 5.9 +/- 0.9, P < 0.001). Both the fasting proinsulin concentration and the ratio of fasting proinsulin to fasting insulin of the type 2 diabetic patients were significantly higher those of the NGT subjects (22.6 pmol/L +/- 14.7 pmol/L vs 11.5 pmol/L +/- 7.1 pmol/L, P < 0.001; and 30.1% +/- 20.5% vs. 12.1% +/- 9.6%, P < 0.001). CONCLUSION: The dysfunction of islet beta-cell in newly diagnosed type 2 diabetic patients is mainly represented by the disappearance of AIR and the evident decline of AUC and HOMA B, and the decrease of quality of insulin secretion.

Adult↗

PubMed2006

Immunoglobulin alpha heavy chain derived from human epithelial cancer cells promotes the access of S phase and growth of cancer cells.

It is generally believed that under normal conditions only B lymphocytes express immunoglobulin. Interestingly, our previous work demonstrated that epithelial cancer tissues and cancer cell lines also express Ig alpha heavy chain. So we further analyzed the potential function of cancer-derived Ig alpha heavy chain. Here we show that blockade of cancer-derived Ig alpha suppressed the growth and viability of cancer cells. And cancer-derived Ig alpha promotes the malignant proliferation ability of cancer cells. Furthermore, we demonstrated that Ig alpha protein increases the access percentage of S phase from the early mitosis of synchronized cancer cells. Our findings support the important role of cancer-derived Ig alpha as a growth promoter of cancer cells, and reveal a novel molecular mechanism for growth and proliferation of cancer cells.

Antibodies, Blocking↗

PubMed2006

Mutagenic effect of cadmium on tetranucleotide repeats in human cells.

Cadmium is a human carcinogen that affects cell proliferation, apoptosis and DNA repair processes that are all important to carcinogenesis. We previously demonstrated that cadmium inhibits DNA mismatch repair (MMR) in yeast cells and in human cell-free extracts (H.W. Jin, A.B. Clark, R.J.C. Slebos, H. Al-Refai, J.A. Taylor, T.A. Kunkel, M.A. Resnick, D.A. Gordenin, Cadmium is a mutagen that acts by inhibiting mismatch repair, Nat. Genet. 34 (3) (2003) 326-329), but cadmium also inhibits DNA excision repair. For this study, we selected a panel of three hypermutable tetranucleotide markers (MycL1, D7S1482 and DXS981) and studied their suitability as readout for the mutagenic effects of cadmium. We used a clonal derivative of the human fibrosarcoma cell line HT1080 to assess mutation levels in microsatellites after cadmium and/or N-methyl-N-nitro-N-nitrosoguanidine (MNNG) exposure to study effects of cadmium in the presence or absence of base damage. Mutations were measured in clonally expanded cells obtained by limiting dilution after exposure to zero dose, 0.5 microM cadmium, 5 nM MNNG or a combination of 0.5 microM cadmium and 5 nM MNNG. Exposure of HT1080-C1 to cadmium led to statistically significant increases in microsatellite mutations, either with or without concurrent exposure to MNNG. A majority of the observed mutant molecules involved 4-nucleotide shifts consistent with DNA slippage mutations that are normally repaired by MMR. These results provide evidence for the mutagenic effects of low, environmentally relevant levels of cadmium in intact human cells and suggest that inhibition of DNA repair is involved.

Base Pair Mismatch↗