Biomedical subjects

Ning Kang

Publications and source records attributed to Ning Kang.

At least 19 recordsLinked to original sources

PubMed2025

Homeobox protein MSX-1 restricts hepatitis B virus by promoting ubiquitin-independent proteasomal degradation of HBx protein.

Hepatitis B virus (HBV) X protein (HBx) is a key factor for regulating viral transcription and replication. We recently characterized homeobox protein MSX-1 (MSX1) as a host restriction factor that inhibits HBV gene expression and genome replication by directly binding to HBV enhancer II/core promoter (EnII/Cp) and suppressing its promoter and enhancer activities. Notably, HBx expression was observed to be repressed more drastically by MSX1 compared to other viral antigens. In this work, we report that in addition to transcriptional repression, MSX1 also post-transcriptionally downregulates HBx protein stability. Mechanistically, MSX1 induces ubiquitin-independent proteasomal degradation of HBx, which is mediated through HBx C-terminal domain. Furthermore, this effect on HBx degradation correlates with MSX1-induced upregulation of DNAJA4 and CRYAB expression. Similar to MSX1, both DNAJA4 and CRYAB promote HBx degradation and repress HBV gene expression and genome replication. In chronic hepatitis B (CHB) patients, immune active phase (IA) is associated with higher intrahepatic expression of MSX1, DNAJA4 and CRYAB, and lower serum HBV markers compared to immune tolerant (IT) phase. Finally, HBV infection is significantly suppressed by MSX1 overexpression in both NTCP-overexpressing cell and humanized liver mouse models. These results demonstrate additional and novel mechanisms of MSX1-mediated repression of HBV, and establish MSX1 as a multi-functional HBV restriction factor with therapeutic potential.

Humans↗

PubMed2006

[Analysis of clinical efficacy and safety of combining pneumatic and ultrasonic power in percutaneous nephrolithotomy (PCNL) for renal stones].

OBJECTIVE: To investigate the clinical efficacy and safety of combining pneumatic and ultrasonic power during PCNL. METHODS: From Sep 2003 to Aug 2005, we treated 486 patients (509 kidneys) by combining pneumatic and ultrasonic power during percutaneous nephrolithotomy. Clinical data were analyzed retrospectively. RESULTS: The percutaneous renal access was successfully established in 478 patients under ultrasound guidance and immediate phase I lithotripsy was performed, and delayed phase II lithotripsy was performed for 6 patients. Average time required for entire procedure is 73 mins, and average time for stone management is 41 mins. No severe complications occurred. No Residual stone fragment in 438 kidneys, stone free rate was 86.1%. Residual stone fragment was found in 71 kidneys by postoperative KUB and received second PCNL or adjuvant ESWL. CONCLUSION: The combined application of pneumatic and ultrasonic power in PCNL appears to be efficacious and safe for disintegrating and removing renal calculi.

Adolescent↗

PubMed2006

[Percutaneous nephrolithotripsy with pneumatic and ultrasonic power under B-type ultrasound guidance for treatment of renal calculi in non-dilated collecting system].

OBJECTIVE: To evaluate the efficacy and safety of management of renal stone in non-dilated collecting system by percutaneous nephrolithotripsy (PCNL) under ultrasound guidance. METHOD: From September 2003 to April 2005, 132 cases of renal stone in non-dilated collecting system were performed by percutaneous nephrolithotripsy. A stent was first inserted into the pelvis through cystoscope, and saline was instilled to dilate collecting system. Antegrade percutaneous access was obtained by B-type ultrasound guidance. A combination pneumatic and ultrasonic lithotrite were used to disintegrate and remove stone under direct vision. Clinical data including operation time, complications and stone free rate were analyzed retrospectively. RESULTS: The percutaneous renal access was successfully established under B-type ultrasound guidance in all patients, immediate phase I lithotripsy was performed in 129 cases and delayed phase II lithotripsy in 3 cases. Operation time ranged from 70 to 130 minutes, average time was (89 +/- 11) minutes, 3 cases were supported by blood transfusion, severe complications did not occur during nephrolithotripsy. Stones were cleared in 114 out of 132 cases (86.4%) during immediate phase I lithotripsy, residual stone fragment was found in 18 cases who received second PCNL or adjuvant extracorporeal shock wave lithotripsy. CONCLUSION: The management of renal stone in non-dilated collecting system using PCNL appears to be efficacious and safe under B-type ultrasound guidance.

Adult↗

PubMed2005

Block copolymer micelles: preparation, characterization and application in drug delivery.

Block copolymer micelles are generally formed by the self-assembly of either amphiphilic or oppositely charged copolymers in aqueous medium. The hydrophilic and hydrophobic blocks form the corona and the core of the micelles, respectively. The presence of a nonionic water-soluble shell as well as the scale (10-100 nm) of polymeric micelles are expected to restrict their uptake by the mononuclear phagocyte system and allow for passive targeting of cancerous or inflamed tissues through the enhanced permeation and retention effect. Research in the field has been increasingly focused on achieving enhanced stability of the micellar assembly, prolonged circulation times and controlled release of the drug for optimal targeting. With that in mind, our group has developed a range of block copolymers for various applications, including amphiphilic micelles for passive targeting of chemotherapeutic agents and environment-sensitive micelles for the oral delivery of poorly bioavailable compounds. Here, we propose to review the innovations in block copolymer synthesis, polymeric micelle preparation and characterization, as well as the relevance of these developments to the field of biomedical research.

Animals↗

PubMed2005

Astrocytic glutamate release-induced transient depolarization and epileptiform discharges in hippocampal CA1 pyramidal neurons.

A paroxysmal depolarization shift (PDS) has been suggested to be a hallmark for epileptic activity in partial-onset seizures. By monitoring membrane potentials and currents in pairs of pyramidal neurons and astrocytes with dual patch-clamp recording and exocytosis of vesicles from astrocytes with two-photon laser scanning microscopy in hippocampal slices, we found that infusion of inositol 1,4,5-trisphosphate (IP(3)) into astrocytes by patch pipettes induced astrocytic glutamate release that triggered a transient depolarization (TD) and epileptiform discharges in CA1 pyramidal neurons. The TD is due to a tetrodotoxin (TTX)-insensitive slowly decaying transient inward current (STC). Astrocytic glutamate release simultaneously triggers both the STC in pyramidal neurons and a transport current (TC) in astrocytes. The neuronal STC is mediated by ionotropic glutamate receptors leading to the TD and epileptiform discharges; while the astrocytic TC is a glutamate reuptake current resulting from transporting released glutamate into the patched astrocyte. Fusion of a large vesicle in astrocytes was immediately followed by an astrocytic TC, suggesting that the fused vesicle contains glutamate. Both fusion of large vesicles and astrocytic TCs were blocked by tetanus toxin (TeNT), suggesting that astrocytic glutamate release is via SNARE-dependent exocytosis of glutamate-containing vesicles. In the presence of TTX, the epileptogenic reagent, 4-AP, also induced similar neuronal STCs and astrocytic TCs, suggesting that astrocytic glutamate release may play an epileptogenic role in initiation of epileptic seizures under pathological conditions. Our study provides a novel mechanism, astrocytic release of glutamate, for seizure initiation.

2-Amino-5-phosphonovalerate↗

PubMed2005

Activity-dependent long-term potentiation of intrinsic excitability in hippocampal CA1 pyramidal neurons.

The efficiency of neural circuits is enhanced not only by increasing synaptic strength but also by increasing intrinsic excitability. In contrast to the detailed analysis of long-term potentiation (LTP), less attention has been given to activity-dependent changes in the intrinsic neuronal excitability. By stimulating hippocampal CA1 pyramidal neurons with synaptic inputs correlating with postsynaptic neuronal spikes, we elicited an LTP of intrinsic excitability (LTP-IE) concurring with synaptic LTP. LTP-IE was manifested as a decrease in the action potential threshold that was attributable to a hyperpolarized shift in the activation curve of voltage-gated sodium channels (VGSCs) rather than activity-dependent changes in synaptic inputs or A-type K+ channels. Cell-attached patch recording of VGSC activities indicated such an activity-dependent change in VGSCs. Induction of LTP-IE was blocked by the NMDA receptor antagonist APV, intracellular BAPTA, the CaM kinase inhibitors KN-62 and autocamtide-2-related inhibitory peptide, and the protein synthesis inhibitors emetine and anisomycin. The results suggest that induction of LTP-IE shares a similar signaling pathway with the late phase of synaptic LTP and requires activation of the NMDA glutamate receptor subtype, Ca2+ influx, activity of CaM kinase II, and function of the protein synthesis. This new form of hippocampal neuronal plasticity could be a cellular correlate of learning and memory besides synaptic LTP.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2005

Plastic changes in interhemispheric inhibition with practice of a two-hand force production task: a transcranial magnetic stimulation study.

We studied the effects of practice of an unusual two-hand finger force production task on electromyographic and force responses to transcranial magnetic stimulation (TMS). Prior to practice, force production by a hand resulted in decreased TMS-induced responses in the other hand. After practice, fingers that were explicitly required to produce force during practice showed a significant drop in these inhibitory effects, while other fingers did not. We conclude that interhemispheric inhibitory projections can show plastic changes that favor the execution of a practiced task.

Adult↗

PubMed2005

Stereocomplex block copolymer micelles: core-shell nanostructures with enhanced stability.

Monodisperse stereocomplex block copolymer micelles were obtained through the self-assembly of equimolar mixtures of poly(ethylene glycol)-block-poly(l-lactide) and poly(ethylene glycol)-block-poly(d-lactide) in water. These micelles possessed partially crystallized cores and mean hydrodynamic diameters ranging from 31 to 56 nm, depending on the lactide content. They exhibited kinetic stability and redispersion properties superior to micelles prepared with isotactic or racemic polymers alone. This study demonstrates the advantages of stereocomplex formation in the design of stabilized water-soluble nanoparticles.

Colloids↗

PubMed2005

White matter fiber tractography via anisotropic diffusion simulation in the human brain.

A novel approach to noninvasively tracing brain white matter fiber tracts is presented using diffusion tensor magnetic resonance imaging (DT-MRI). This technique is based on successive anisotropic diffusion simulations over the human brain, which are utilized to construct three dimensional diffusion fronts. The fiber pathways are determined by evaluating the distance and orientation from the fronts to their corresponding diffusion seeds. Synthetic and real DT-MRI data are employed to demonstrate the tracking scheme. It is shown that the synthetic tracts are accurately replicated, and several major white matter fiber pathways can be reproduced noninvasively, with the tract branching being allowed. Since simulating the diffusion process, which is truly a physical phenomenon reflecting the underlying architecture of cerebral tissues, makes full use of the diffusion tensor data, including both the magnitude and orientation information, the proposed approach is expected to enhance robustness and reliability in white matter fiber reconstruction.

Algorithms↗

PubMed2004

Learning multi-finger synergies: an uncontrolled manifold analysis.

We used the uncontrolled manifold (UCM) approach to study the synergy formation during learning an unusual multi-finger task. The subjects produced accurate force ramps with challenging sets of four fingers (two per hand). We tested hypotheses on stabilization of the contributions of subsets of effectors to the task force ( F(TASK)) and to the moment in the frontal plane (force-stabilization and moment-stabilization, respectively). Force signals were used to compute magnitudes of hypothetical independent signals, modes. The variance of the mode magnitudes across repetitions of the task was partitioned into two components, within the UCM ( V(UCM)), which did not affect the average value of a selected performance variable (force or moment), and orthogonal to the UCM ( V(ORT)), which affected the variable. Prior to practice, subjects showed high error indices and failed to show stabilization of each hand's contribution to F(TASK) ( V(ORT)> or = V(UCM)), while the pronation-supination moment was stabilized by the fingers of each hand ( V(ORT)< V(UCM)). The total forces produced by each of the two hands showed negative covariation across trials, which supported the force-stabilization hypothesis but not moment-stabilization hypothesis. Both force-stabilization and moment-stabilization hypotheses were supported by analysis of mode magnitudes to all eight fingers. Over 2 days of practice, the performance of the subjects improved considerably. This was accompanied by the emergence of within-a-hand force-stabilization for each of the two hands without deterioration of moment-stabilization. Quantitatively better within-a-hand force-stabilization was seen in male subjects as compared to females throughout the course of the experiment. Force-stabilization by all eight fingers improved quantitatively with practice. Practice also resulted in higher finger forces in maximal force production (MVC) trials and higher forces produced by unintended fingers in single-finger MVC trials (higher enslaving). We conclude that the UCM approach allows quantifying changes in the coordination of effectors during practice, and offers insights into the microstructure of this coordination with respect to different performance variables and different subsets of effectors. The approach can be used to test whether new synergies emerge in the process of practice.

Adult↗

PubMed2004

Presynaptic inactivation of action potentials and postsynaptic inhibition of GABAA currents contribute to KA-induced disinhibition in CA1 pyramidal neurons.

Kainate-type glutamate ionotropic receptors (KAR) mediate either depression or potentiation of inhibitory transmission. The mechanisms underlying the depressant effect of KAR agonists have been controversial. Under dual patch-clamp recording techniques in synaptically coupled pairs of CA1 interneurons and pyramidal neurons in hippocampal slices, micromolar concentrations of KAR agonists, kainic acid (KA, 10 microM) and ATPA (10 microM), induced inactivation of action potentials (APs) in 58 and 50% of presynaptic interneurons, respectively. Inactivation of interneuronal APs might have significantly contributed to KA-induced decreases in evoked inhibitory postsynaptic currents (eIPSCs) that are obtained by stimulating the stratum radiatum. With controlled interneuronal APs, KAR agonists induced a decrease in the potency (mean amplitude of successful events) and mean amplitude (including failures) of unitary inhibitory postsynaptic currents (uIPSCs) without significantly changing the success rate (P(s)) at perisomatic high-P(s) synapses. In contrast, KAR agonists induced a decrease in both the P(s) and potency of uIPSCs at dendritic high-P(s) synapses. KAR agonists induced an inhibition of GABA(A) currents by activating postsynaptic KARs in pyramidal neurons; this was more prominent at dendrites than at soma. Both the exogenous GABA-induced current and the amplitude of miniature IPSCs (mIPSCs) were attenuated by KAR agonists. Thus the postsynaptic KAR-mediated inhibition of GABA(A) currents may contribute to the KAR agonist-induced decrease in the potency of uIPSCs and KA-induced disinhibition.

Action Potentials↗

PubMed2004

[Role of telomerase in chrysotile induced malignant transformation of normal human embryonic lung fibroblasts].

OBJECTIVE: To explore the role of telomerase in asbestos dust induced malignant transformation of human embryonic lung fibroblasts in vitro. METHODS: Human telomerase catalytic subunit (hTERT) was transferred into human embryonic lung fibroblasts (HELF). Chrysotile dust at concentration of 2.5 microg/cm(2) was added to HELF transduced with and without hTERT (HELF-T+), respectively, and their transduced foci were separated. Biological characteristics of the cells, telomerase activity, length of telomere and cell growth curve were observed. Colony forming test was performed on soft agar to evaluate the nature of transformation. RESULTS: The hTERT gene was transferred into HELF steadily, and HELF-T+ was established. Malignant transformation occurred in both HELF and HELF-T+ by asbestos stimulation. Asbestos dusts could induce higher rate of transformations in HELF-T+ [(2.08 +/- 1.08)/utensil] than in HELF [(1.08 +/- 0.10)/utensil], P < 0.05. Telomerase activity in both transformed malignant cells and HELF-T+ was higher, as well as the longer length of telomere in them. CONCLUSION: Rate of malignant transformation in cells with more activity of telomerase and longer length of the telomere was higher after stimulation with asbestos, indicating telomerase could play an important role in asbestos induced human cells malignant transformation.

Asbestos, Serpentine↗

PubMed2004

[Role of telomerase in silica induced human cell transformation].

OBJECTIVE: To explore the role of telomerase in silica induced human cell transformation in vitro. METHODS: Human telomerase catalytic subunit (hTERT) was transferred into human embryonic lung fibroblasts (HELF). 160 microg/cm2 silica dusts were added to transform HELF and hTERT transduced HELF (HELF-T+) respectively. The telomerase activity and the length of telomere were determined. The growths of the normal and transformed cells were evaluated. RESULTS: The hTERT gene was steadily transferred into HELF. Silica dusts caused the transformations of both HELF-T+ and HELF. The telomerase activities in transformed cells were higher and the telomere length of transformed cells was longer than those of HELF. CONCLUSION: The changes of telomerase activity and telomere length may play an important role in the silica induced human cells transformation.

Cell Line↗

PubMed2004

[The role of cycline dependent kinase 4 in the malignant transformation induced by silica].

OBJECTIVE: To study the role of cycline dependent kinase 4 (CDK4) in the malignant transformation of human fetal lung diploid fibroblast cell (2BS) induced by silica. METHODS: Recombination vectors with antisense pXJ41-CDK4 were constructed, and then were transfected into the malignant transformed cells induced by silica. In situ hybridization and immunohistochemistry were used to analyze the expression of CDK4. Cell growth curve, doubling time, cell cycle distribution and the growth capacities on soft agar were analyzed before and after antisense CDK4 RNA was transferred into malignant transformed cells induced by silica. RESULTS: During the malignant transformation of 2BS cells induced by silica, CDK4 gene was overexpressed. Antisense pXJ41-CDK4 transduction suppressed CDK4 gene expression in the antisense pXJ41-CDK4 transfected cells. Antisense CDK4 RNA led to cell cycle arrest, resulting in lengthened G1 phase (the percentages of cells in the G1 phase increased from 45.1% to 58.0%), and eventually attenuated the proliferation of malignant transformed cells induced by silica. At the 8th day, the suppression rates decreased by 77.43%. The doubling time prolonged from 21.0 h to 42.7 h. The growth capacities on soft agar of cells transfected by antisense pXJ41-CDK4 were decreased. CONCLUSION: CDK4 might play an important role in maintaining the transformed phenotype of the cancer cells.

Cell Transformation, Neoplastic↗

PubMed2004

[Role of cyclin D1 in carcinogenesis of human cells induced by quartz].

OBJECTIVE: To study the role of cyclin D1 in malignant transformation of human embryonic lung diploid fibroblasts (HELF) induced by quartz. METHODS: pXJ41-cyclin D1 expressing sense and antisense cyclin D1 RNA were transinfected into malignant transformed HELF induced by quartz with DNA recombination and gene transduction. The expression of cyclin D1 was detected with hybridization in situ and immunohistochemistry methods to analyze changes in cell growth, double multiplication time, distribution of cell cycles, colony forming ability on soft agar, etc., before and after cyclin D1 transduction. RESULTS: During the process of malignant transformation of HELF induced by quartz, cyclin D1 gene was overexpressed. Antisense pXJ41-cyclin D1 RNA could suppress the growth and proliferation of malignant transformed cells induced by quartz. Growth speed of antisense pXJ41-cyclin D1 transinfected cells decreased by 58.69% on the 8th day in culture, as compared to malignant transformed cells induced by quartz, and its double multiplication time prolonged from 21.0 h to 31.4 h. Antisense cyclin D1 RNA led to cell cycle arrest, resulting in lengthened G1 phase (proportion of cells in phase G1 increased to 52.7% from 45.1% and that of cells in phase S decreased to 33.1% from 40.3%). Colony forming rate reduced significantly and size of colony became smaller. CONCLUSIONS: Abnormal expression of cyclin D1 in cells related to their malignant transformation induced by quartz. Highly expressed cyclin D1 could play an important role in maintaining the transformed phenotype of malignant cells.

Cell Transformation, Neoplastic↗

PubMed2003

Uncontrolled manifold analysis of single trials during multi-finger force production by persons with and without Down syndrome.

Recently, the framework of the uncontrolled manifold (UCM) hypothesis has been used to study multi-finger synergies based on analysis of motor variability across large sets of trials. We introduce a similar method of analysis, which can be applied to single trials, and hence may be more relevant to studies of atypical populations. In one experiment, results of across-trials and single-trial UCM analysis were compared for control participants who performed accurate ramp force production trials by pressing with four fingers of the hand. Both types of analysis revealed selective stabilization of total force by co-variations of individual finger forces. The stabilization was more pronounced at higher forces. When the participants purposefully varied the relative involvement of fingers during the ramp, significantly higher UCM effects were observed. However, high-pass filtering of the data at 4 Hz made these results similar to those observed in trials with natural patterns of force production. These observations allow assessment of the contribution of processes at two levels of a hypothetical hierarchical control system to the stabilization of total force. We also applied the single-trial UCM method to re-analyze previously published data from another experiment to study the motor variability in a group of persons with Down syndrome (DS) because these persons have difficulty in motor planning and timing as well as in force stabilization. Results of single-trial UCM analysis demonstrated force stabilization in these persons. The degree of force stabilization improved significantly after three days of practice. The analysis also showed that the total pronation/supination moment generated by the four fingers with respect to the midpoint was stabilized. The degree of moment stabilization did not change with practice. We conclude that the single-trial method of UCM analysis allows the analysis of hypotheses about stabilization of different performance variables by alleged multi-finger synergies in both typical individuals and individuals with DS.

Adolescent↗

PubMed2003

[Deletion of p15 and p16 genes and overexpression of STK15 gene in human laryngeal squamous cell carcinoma].

OBJECTIVE: To investigate the association of p15 and p16 genes deletion, and STK15 gene overexpression with laryngeal squamous cell carcinoma (LSCC). METHODS: The cancer tissue and surrounding normal tissue were taken during operation from 50 cases of LSCC who had undergone neither chemotherapy nor radiotherapy preoperatively. DNA was extracted and PCR was used to test the homozygous deletion of p15 exon 2 (p15E2) and p16 exon 2 (p16E2). RNA was extracted, cDNA was synthesized by reverse transcription, and the expression of STK15 gene was tested by PCR with beta-actin as inner control. At the same time the expression of STK15 in human LSCC Hep-2 cell line was tested. The ratio of ADV (average density value) of STK15 gene to the ADV of beta-actin gene was calculated. RESULTS: The rate of p15E2 deletion was 12% (6/50) and that of p16E2 was 14% (7/50). The p15E2 and p16E2 codeletion rate was 6% (3/50). In 34 of the 50 cases (68%) the expression of STK15 gene in tumor tissue was higher than that of the paired surrounding normal tissue with a significant difference. The ratio of ADV of STK15 gene to ADV of beta-actin gene was 1.03 +/- 0.30 in the cancer tissue, and 0.89 +/- 0.22 in the paired normal tissue with a significant difference (t = 4.333, P < 0.01). The expression of STK15 gene was higher than that of beta-actin in Hep-2 cell line. CONCLUSION: The homozygous deletion of p15E2 and p16E2 and overexpression of STK15 gene may play a role in the oncogenesis and malignant progression of laryngeal squamous cell carcinoma.

Aurora Kinase A↗

PubMed2003

[Recombination and identification of sense and antisense cyclinD1 eukaryotic expression vectors].

The exogenous gene cyclinD1 cDNA was inserted into eukaryotic expression vector pXJ41-neo by gene transduction and recombination techniques. The recombinant was detected by electrophoresis. Results showed that the recombinant sense plasmid (pXJ41-cyclinD1) was digested by HindIII into 229 bp, 427 bp and 7554 bp; while the recombinant antisense plasmid was digested into 427 bp, 1184 bp and 6599 bp, implying that sense and antisense pXJ41-cyclinD1 eukaryotic expression vectors were successfully recombined. The finding from this study offers an effective tool to reveal the mechanism of the carcinogenesis of environmental and occupational hazards.

Antisense Elements (Genetics)↗