Biomedical subjects

Dan Hu

Publications and source records attributed to Dan Hu.

18 recordsLinked to original sources

PubMed2026

Induction Paclitaxel-Cisplatin-Capecitabine for Nasopharyngeal Carcinoma.

BACKGROUND: We previously reported higher failure-free survival (FFS) with induction paclitaxel, cisplatin, and capecitabine (TPC) compared with cisplatin and fluorouracil (PF) in high-risk locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We now report 5-year FFS, with prespecified secondary outcomes. METHODS: In this multicenter, randomized trial, patients with high-risk LA-NPC (T4N0-2M0 or TanyN3M0) received two 21-day cycles of induction chemotherapy with TPC or PF, followed by concurrent chemoradiotherapy. The primary endpoint was FFS; secondary endpoints included distant metastasis-free, locoregional relapse-free, and overall survival (OS), tumor response, and safety. RESULTS: Among 238 patients (TPC, n=118; PF, n=120), with median follow-up of 89.1 months, 5-year FFS was 77.6% in the TPC group and 62.9% in the PF group (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.34-0.82). At 5 years, distant metastasis-free survival was 87.8% in the TPC group and 78.8% in the PF group (HR, 0.51; 95% CI, 0.28-0.95); locoregional relapse-free survival was 92.0% and 82.1%, respectively (HR, 0.43; 95% CI, 0.21-0.88); and OS was 89.6% and 82.2%, respectively (HR, 0.51; 95% CI, 0.27-0.95). Among patients with pretreatment Epstein-Barr virus (EBV) DNA <3000 copies/ml, 5-year OS was 92.3% in the TPC group and 84.4% in the PF group. Among those with higher EBV DNA levels, rates were 84.2% in TPC group and 81.1% in PF group. Grade 3 or 4 adverse events occurred in 68 patients (57.6%) receiving TPC and 79 patients (65.8%) receiving PF. Treatment adherence was similar in the two groups. CONCLUSIONS: Among patients with high-risk LA-NPC, TPC induction chemotherapy was associated with higher 5-year FFS than PF. (Funded by National Natural Science Foundation of China and State Key Laboratory of Respiratory Disease; ClinicalTrials.gov number, NCT02940925.).

Humans↗

PubMed2006

Compound heterozygous mutations P336L and I1660V in the human cardiac sodium channel associated with the Brugada syndrome.

BACKGROUND: Loss-of-function mutations in SCN5A have been associated with the Brugada syndrome. We report the first Brugada syndrome family with compound heterozygous mutations in SCN5A. The proband inherited 1 mutation from each parent and transmitted 1 to each daughter. METHODS AND RESULTS: The effects of the mutations on the function of the sodium channel were evaluated with heterologous expression in TSA201 cells, patch-clamp study, and confocal microscopy. Genetic analysis revealed that the proband carried 2 heterozygous missense mutations (P336L and I1660V) on separate alleles. He displayed a coved-type ST-segment elevation and a prolonged PR interval (280 ms). One daughter inherited P336L and exhibited a prolonged PR (210 ms). The other daughter inherited mutation I1660V and displayed a normal PR interval. Both daughters had a slightly elevated, upsloping ST-segment elevation. The parents had normal ECGs. Patch-clamp analysis showed that the P336L mutation reduced I(Na) by 85% relative to wild type. The I1660V mutation produced little measurable current, which was rescued by room temperature incubation for 48 hours. Sodium channel blockers also rescued the I1660V current, with mexiletine proving to be the most effective. Confocal immunofluorescence showed that I1660V channels conjugated to green fluorescent protein remained trapped in intracellular organelles. CONCLUSIONS: Mutation P336L produced a reduction in cardiac I(Na), whereas I1660V abolished it. Only the proband carrying both mutations displayed the Brugada syndrome phenotype, whereas neither mutation alone produced the clinical phenotype. I1660V channels could be rescued pharmacologically and by incubation at room temperature. The present data highlight the role of compound heterozygosity in modulating the phenotypic expression and penetrance of Brugada syndrome.

Brugada Syndrome↗

PubMed2006

Apparent suppression of MMP-9 activity by GD1a as determined by gelatin zymography.

Gelatin zymography is widely used to detect and evaluate matrix metalloproteinase-9 (MMP-9) activity. MMP-9 transcription was previously shown to be negatively regulated by ganglioside GD1a [D. Hu, Z. Man, T. Xuan, P. Wang, T. Takaku, S. Hyuga, X.S. Yao, T. Sato, S. Yamagata, T. Yamagata, Ganglioside GD1a regulation of matrix metalloproteinase-9 (MMP-9) expression in mouse FBJ cell Lines: GD1a suppression of MMP-9 expression stimulated by PI3K-Akt and p38 though not by the Erk signaling pathway, 2006, submitted for publication.]. Zymography of MMP-9 of FBJ-M5 cells preincubated with GD1a indicated a greater decrease in activity than expected from mRNA suppression. Incubation of conditioned medium containing MMP-9 with GD1a caused MMP-9 activity to decrease. Examination was thus made to confirm that MMP-9 activity is actually suppressed and/or MMP-9 protein undergoes degradation by GD1a. GD1a was found to have no effect on MMP-9 activity and Western blots indicated GD1a not to diminish MMP-9 during electrophoresis under reducing conditions. GD1a appeared to mediate the binding of a portion of MMP-9 with certain molecules, with consequently greater molecular mass on the gel, to cause decrease in the activity of MMP-9 at the site where it would normally appear. Caution should be used in doing gelatin zymography since molecules other than GD1a may similarly work, causing decrease in MMP-9 activity in zymography.

Animals↗

PubMed2006

External Qi of Yan Xin Qigong differentially regulates the Akt and extracellular signal-regulated kinase pathways and is cytotoxic to cancer cells but not to normal cells.

Long-term clinical observations and ongoing studies have shown significant antitumor effect of external Qi of Yan Xin Qigong which originated from traditional Chinese medicine. In order to understand the molecular and cellular mechanisms underlying the antitumor effect of external Qi of Yan Xin Qigong, we have examined its cytotoxic effect on BxPC3 pancreatic cancer cells and its effect on the Akt and extracellular signal-regulated kinase pathways. We found that external Qi of Yan Xin Qigong dramatically inhibited basal phosphorylation levels of Akt and extracellular signal-regulated kinases, epidermal growth factor-mediated phosphorylation of extracellular signal-regulated kinases, and phosphatidylinositol 3-kinase activity. External Qi of Yan Xin Qigong also inhibited constitutive and inducible activities of nuclear factor-kappa B, a target of the Akt and epidermal growth factor receptor pathways. Furthermore, a single 5min exposure of BxPC3 cells to external Qi of Yan Xin Qigong induced apoptosis, accompanied by a dramatic increase of the sub-G1 cell population, DNA fragmentation, and cleavage of caspases 3, 8 and 9, and poly(ADP-ribose) polymerase. Prolonged treatment with external Qi of Yan Xin Qigong caused rapid lysis of BxPC3 cells. In contrast, treatment of fibroblasts with external Qi of Yan Xin Qigong induced transient activation of extracellular signal-regulated kinases and Akt, and caused no cytotoxic effect. These findings suggest that external Qi of Yan Xin Qigong may differentially regulate these survival pathways in cancer versus normal cells and exert cytotoxic effects preferentially on cancer cells, and that it could potentially be a valuable approach for therapy of pancreatic carcinomas.

Breathing Exercises↗

PubMed2006

Ganglioside GD1a regulation of caveolin-1 and Stim1 expression in mouse FBJ cells: augmented expression of caveolin-1 and Stim1 in cells with increased GD1a content.

GD1a was previously shown responsible for regulating cell motility, cellular adhesiveness to vitronectin, phosphorylation of c-Met and metastatic ability of mouse FBJ osteosarcoma cells. To determine the particular molecules regulated by GD1a, FBJ cells were assessed for tumor-related gene expression by semi-quantitative RT-PCR. Caveolin-1 and stromal interaction molecule 1 (Stim1) expression in FBJ-S1 cells, rich in GD1a, were found to be 6 and 4 times as much, respectively, than in FBJ-LL cells devoid of GD1a. Enhanced production of caveolin-1 in protein was confirmed by Western blotting. A low-metastatic FBJ-LL cell variant, having high GD1a expression through beta1-4GalNAcT-1 (GM2/GD2 synthase) cDNA transfection (Hyuga S, et al, Int J Cancer 83: 685-91, 1999), showed enhanced production of caveolin-1 and Stim1 in mRNA and protein, compared to mock-transfectant M5. Incubation of FBJ-M5 cells with exogenous GD1a augmented the expression of caveolin-1 in mRNA and protein and Stim1 in mRNA as well. Treatment of FBJ-S1 with fumonisin B1, an inhibitor of N-acylsphinganine synthesis, for 15 days caused the complete depletion of gangliosides and suppressed the expression of caveolin-1 and Stim1. St3gal5 siRNA transfected cells showed decreased expression of caveolin-1 and Stim1 mRNA, as well as St3gal5 mRNA. These findings clearly indicate ganglioside GD1a to be involved in the regulation of the transformation suppressor genes, caveolin-1 and Stim1. Moreover, treatment with GD1a of mouse melanoma B16 cells and human hepatoma HepG2 cells brought about elevated expression of caveolin-1 and Stim1.

Animals↗

PubMed2006

Vicarious trial-and-error behavior and hippocampal cytochrome oxidase activity during Y-maze discrimination learning in the rat.

The present study investigated whether more vicarious trial-and-error (VTE) behavior, defined by head movement from one stimulus to another at a choice point during simultaneous discriminations, led to better visual discrimination learning in a Y-maze, and whether VTE behavior was a function of the hippocampus by measuring regional brain cytochrome oxidase (C.O.) activity, an index of neuronal metabolic activity. The results showed that the more VTEs a rat made, the better the rat learned the visual discrimination. Furthermore, both learning and VTE behavior during learning were correlated to C.O. activity in the hippocampus, suggesting that the hippocampus plays a role in VTE behavior during discrimination learning.

Analysis of Variance↗

PubMed2006

[A comparative study on biocompatibility of acellular corneal stroma materials prepared by serial digestion methods].

OBJECTIVE: To observe the biocompatibility of the acellular corneal stroma materials prepared by three different methods. METHODS: Three different serial digestion methods were used to produce the acellular corneal stroma materials. The biocompatibility of the materials was investigated by the cell seeding and the materials were implanted into the rabbit corneal stroma layer. RESULTS: The cells in the materials 1 and 2 were not decellularized completely. The rabbit corneal fibroblasts died on the materials 1 and 2 after the cell seeding for 3-4 days. An obvious rejection could be observed after the implantation. The cells in material 3 were decellularized completely and the collagen fibers or elastic fibers were reserved integrally, showing a typical three-dimensional network. The rabbit corneal fibroblasts could expand on the materials in vitro. No obvious rejection could be observed and the materials were gradually absorbed. CONCLUSION: The acellular porcine cornea stroma materials prepared by trypsin-Dnase-Rnase are suitable for reconstruction of the tissue engineered cornea.

Animals↗

PubMed2005

Activity of striatal neurons reflects dynamic encoding and recoding of procedural memories.

Learning to perform a behavioural procedure as a well-ingrained habit requires extensive repetition of the behavioural sequence, and learning not to perform such behaviours is notoriously difficult. Yet regaining a habit can occur quickly, with even one or a few exposures to cues previously triggering the behaviour. To identify neural mechanisms that might underlie such learning dynamics, we made long-term recordings from multiple neurons in the sensorimotor striatum, a basal ganglia structure implicated in habit formation, in rats successively trained on a reward-based procedural task, given extinction training and then given reacquisition training. The spike activity of striatal output neurons, nodal points in cortico-basal ganglia circuits, changed markedly across multiple dimensions during each of these phases of learning. First, new patterns of task-related ensemble firing successively formed, reversed and then re-emerged. Second, task-irrelevant firing was suppressed, then rebounded, and then was suppressed again. These changing spike activity patterns were highly correlated with changes in behavioural performance. We propose that these changes in task representation in cortico-basal ganglia circuits represent neural equivalents of the explore-exploit behaviour characteristic of habit learning.

Acoustic Stimulation↗

PubMed2005

Hippocampal cytochrome oxidase activity of rats in easy and difficult visual discrimination learning.

The present study investigated the functional involvement of the rat hippocampal formation in easy and difficult visual discrimination learning by measuring regional brain cytochrome oxidase (C.O.) activity, an index of neuronal metabolic activity. The results showed that learning was related to C.O. activity in the CA field and the dentate gyrus of the hippocampal formation of rats in the difficult discrimination, whereas learning was related to C.O. activity only in the dentate gyrus of rats in the easy discrimination. The results suggest that difficult visual discrimination learning required greater involvement of the hippocampal formation than easy visual discrimination learning.

Animals↗

PubMed2005

[Expression of heat shock protein 72 in leukocytes from patients with acute trauma and its relationship with survival].

OBJECTIVE: To determine the expression of heat shock protein 72 (HSP 72) in leukocytes of patients with acute trauma, and evaluate its relationship with survival. METHODS: Thirty acute trauma patients with acute physiology and chronic health evaluation III (APACHE III) > or = 18 were included as study subjects. Blood samples were serially obtained at three time points: days 0-1, days 2-6 and days 7-14 after the trauma. Expression of HSP72 was assessed with immunohistochemistry, and the expression of HSP72 mRNA was assessed with semi-quantified reverse transcription-polymerase chain reaction (RT-PCR), and the relationship between their levels and the survival rate (survival period > 2 months) was analyzed. RESULTS: The expression of HSP72 was significantly enhanced on post-trauma days 2-6. The levels of HSP72 in the survivor groups were higher than that in non-survivors. CONCLUSION: The study suggests that acute trauma can lead to a marked elevation of HSP72, and its peak level appears on days 2-6, which might be correlated with 2-month survival of the afflicted patients.

APACHE↗

PubMed2004

Analysis of regulatory CD8 T cells in Qa-1-deficient mice.

The mouse protein Qa-1 (HLA-E in humans) is essential for immunological protection and immune regulation. Although Qa-1 has been linked to CD8 T cell-dependent suppression, the physiological relevance of this observation is unclear. We generated mice deficient in Qa-1 to develop an understanding of this process. Qa-1-deficient mice develop exaggerated secondary CD4 responses to foreign and self peptides. Enhanced responses to proteolipid protein self peptide were associated with resistance of Qa-1-deficient CD4 T cells to Qa-1-restricted CD8 T suppressor activity and increased susceptibility to experimental autoimmune encephalomyelitis. These findings delineate a Qa-1-dependent T cell-T cell inhibitory interaction that prevents the pathogenic expansion of autoreactive CD4 T cell populations and consequent autoimmune disease.

Animals↗

PubMed2004

Dynamic analysis of learning in behavioral experiments.

Understanding how an animal's ability to learn relates to neural activity or is altered by lesions, different attentional states, pharmacological interventions, or genetic manipulations are central questions in neuroscience. Although learning is a dynamic process, current analyses do not use dynamic estimation methods, require many trials across many animals to establish the occurrence of learning, and provide no consensus as how best to identify when learning has occurred. We develop a state-space model paradigm to characterize learning as the probability of a correct response as a function of trial number (learning curve). We compute the learning curve and its confidence intervals using a state-space smoothing algorithm and define the learning trial as the first trial on which there is reasonable certainty (>0.95) that a subject performs better than chance for the balance of the experiment. For a range of simulated learning experiments, the smoothing algorithm estimated learning curves with smaller mean integrated squared error and identified the learning trials with greater reliability than commonly used methods. The smoothing algorithm tracked easily the rapid learning of a monkey during a single session of an association learning experiment and identified learning 2 to 4 d earlier than accepted criteria for a rat in a 47 d procedural learning experiment. Our state-space paradigm estimates learning curves for single animals, gives a precise definition of learning, and suggests a coherent statistical framework for the design and analysis of learning experiments that could reduce the number of animals and trials per animal that these studies require.

Algorithms↗

PubMed2004

Plasmacytoid dendritic cells activate lymphoid-specific genetic programs irrespective of their cellular origin.

The developmental origin of type I interferon (IFN)-producing plasmacytoid dendritic cells (PDCs) is controversial. In particular, the rearrangement of immunoglobulin heavy chain (IgH) genes in murine PDCs and the expression of pre-T cell receptor alpha (pTalpha) gene by human PDCs were proposed as evidence for their "lymphoid" origin. Here we demonstrate that PDCs capable of IFN production develop efficiently from both myeloid- and lymphoid-committed progenitors. Rearranged IgH genes as well as RAG transcripts were found in both myeloid- and lymphoid-derived PDCs. The human pTalpha transgenic reporter was activated in both myeloid- and lymphoid-derived PDCs at a level comparable to pre-T cells. PDCs were the only cell population that activated murine RAG1 knockin and human pTalpha transgenic reporters outside the lymphoid lineage. These results highlight a unique developmental program of PDCs that distinguishes them from other cell types including conventional dendritic cells.

Animals↗

PubMed2004

Adenovirally delivered brain-derived neurotrophic factor to rat retina.

PURPOSE: To study the expression of brain-derived neurotrophic factor (BDNF) in the rat retina delivered by adenovirus. METHODS: Adenovirus with BDNF gene was injected into the vitreous. Gene expression was detected by immunofluorescence staining,and quantitative analysis was performed after injury and transfection by Enzyme-linked immunosorbent assay (ELISA). RESULTS: The positive cells can be seen on the 3rd day and last 4 weeks by immunofluorescence staining. Positive cells in the control group were fewer than those in the transfection group or the fluorescence intensity was lower at every time point. Quantitative analysis showed that the expression of BDNF groups was higher than that of the control group at every time point (P < 0.01), and that of the injured group without transfection was higher than that of the control group on the 3rd day and the 7th day (P < 0.01). CONCLUSION: Efficient and stable transfer of BDNF gene could be achieved by adenovirus delivery into the retina of rats. Injury can promote the expression of BDNF in early period.

Adenoviridae↗

PubMed2004

[Ecological service assessment of human-dominated freshwater ecosystem with a case study in Yangzhou Prefecture, China.

Freshwater ecosystems provide a host of services to humanity. These services are now rapidly being lost, not least because of the inability of making the impacts measurable. To overcome this obstacle, assessment frameworks for freshwater ecosystem services are needed. A simple water equivalent framework to assess the ecological services provided by freshwater ecosystems was developed in this study. It translated the occupation of freshwater ecosystem services into biologically freshwater volumes and then compares this consumption to the freshwater throughput, that is, the ecological capacity available in this region. In this way, we use the example of Yangzhou Prefecture, to account the main categories of human occupation of water ecosystem services. The result showed that there is a huge gap between the consumption and the supply of freshwater ecosystem services. This must encourage local government to make land-use and water management decisions both economically rational and environmentally sound.

China↗

PubMed2003

Expression, purification and functional characterization of a recombinant scorpion venom peptide BmTXKbeta.

BmTXKbeta, a scorpion toxin isolated from the Chinese scorpion Buthus martensii Karsch (BmK), was expressed as a GST fusion protein in BL21 (DE3) strain. The recombinant GST-BmTXKbeta protein was purified by affinity chromatography. When treated with enterokinase, the GST-BmTXKbeta fusion protein released an approximate 6.5kDa protein which was the expected size for correctly processed. About 2mg purified recombinant BmTXKbeta protein (rBmTXKbeta) was produced from 1l bacterial culture, using this expression and purification system. The function of rBmTXKbeta was studied on the rabbit atrial myocyte by whole-cell patch clamp technique. The results showed that rBmTXKbeta inhibited the transient outward current (I(to)) of rabbit atrial myocyte with recovery after washout and the inhibition was concentration-dependent. The rBmTXKbeta prolonged the action potential duration of rabbit atrial myocyte in a concentration-dependent manner, whereas it did not affect the action potential amplitude.

Action Potentials↗

PubMed2003

Effects of BmkTXK beta on electrophysiological properties of rabbit atrial myocytes.

OBJECTIVE: To investigate the effects of BmkTXK(beta), a newly purified 'long chain' peptide inhibitor of K(+) channels from the Chinese scorpion Buthus martensi Karsch (BmK), on the electrophysiological properties of isolated rabbit atrial myocytes. METHODS: The standard whole-cell patch-clamp technique was used to study the effects of multiple concentrations of BmkTXK(beta) on potassium currents and action potentials. RESULTS: BmkTXK(beta) produced concentration-dependent prolongation of action potential duration at 20%, 50%, and 90% repolarization (APD(20,50,90)) without any use-dependence. Meanwhile, it had no significant effect on RMP, APA, or V(max) (n = 9). At a dose of 1 micro mol/L, BmkTXK(beta) decreased I(to) by 41.4% (n = 10, P < 0.01) at a membrane potential of +50 mV [from (13.63 +/- 0.87) pA/pF to (7.98 +/- 0.78) pA/pF]. I(to) was reduced significantly with an IC(50) value of 1.82 micromol/L (95% confidence interval: 1.47 - 2.17 micro mol/L), in a clear concentration-dependent manner. BmkTXK(beta) blocked I(Ks) and I(Ks),tail with an IC(50) of 20.15 micromol/L and a 95% confidence interval of 16.93 - 23.37 micromol/L. At a concentration of 10 micromol/L, BmkTXK(beta) blocked both I(Ks) (mean reduction 37.3% +/- 4.2%, P < 0.01, n = 7) and I(Ks), tail (mean reduction 35.8% +/- 4.1%, P < 0.01, n = 7). At 0 mV, 10 micromol/L BmkTXK(beta) inhibited both I(Kr) (mean reduction 40.5% +/- 2.6%, P < 0.01, n = 6) and I(Kr), tail (mean reduction 42.3% +/- 2.9%, P < 0.01, n = 6). Blocking of I(Kr) by BmkTXK(beta) occurred in a concentration-dependent manner, with an IC(50) of 17.21 micromol/L (95% confidence interval: 14.76-19.66 micromol/L). An absence of effects on I(K1) was observed for BmkTXK(beta), with no change in reversal-potential (n = 6, P > 0.05). CONCLUSIONS: BmkTXK(beta) exerts direct blocking effects on several potassium channels involved in cardiac repolarization, and has a strong effect on prolonging the repolarization of rabbit cardiomyocytes without reverse frequency dependence. This finding suggests that BmkTXK(beta) could be a promising class III drug for anti-arrhythmic therapy without the risk of proarrhythmia.

Action Potentials↗

PubMed2002

[Effect of adenovirally delivered brain-derived neurotrophic factor on superoxide dismutase within the retina of experimentally injured optic nerve of rat eyes].

PURPOSE: To study the changes of malondialdehyde(MDA) and superoxide dismutase (SOD) in the retinal tissues of the rats after optic nerve injury and the influence to it by adenovirally delivered brain-derived neurotrophic factor (BDNF) to ocular tissues. METHODS: Adenovirus with BDNF gene, adenovirus with beta-galactosidase gene and balanced salt solution were injected, respectively, into vitreous of injured eyes of rat. The content of MDA and SOD in the retinal tissues of the rats were measured by means of quantity analysis in various time. That of normal retinal tissues were examined and used as control. RESULTS: The content of MDA and SOD in the normal retina was (5.33 +/- 1.45) nmol/ ml (21d), fewer than the two control groups' and the contents of SOD of BDNF group were (1587.55 +/- 173.39) U/g x pro (3d), (1613.24 +/- 184.57) U/g x pro(7d) (1694. 49 +/- 184. 30) U/g x pro (14d) and (1721.75 +/- 179.86) U/g x pro(21d), more than the two control groups' meanwhile. There were significent differences at 3d, 1 wk and 2 wk (P < 0.05). There were no significent differences between the two control groups at every time point. CONCLUSION: Adenovirally delivered BDNF to murine ocular tissues after optic nerve injury helps protect from oxidative stress during earlier period. The effect may be related to the increased amount of SOD within local tissue by BDNF.

Adenoviridae↗