Biomedical subjects

Bing Hu

Publications and source records attributed to Bing Hu.

At least 19 recordsLinked to original sources

PubMed2026

Advancing precision tacrolimus therapy: a systems genetics dissection in BXD platform.

BACKGROUND: Tacrolimus is a core immunosuppressant in organ transplantation, but its narrow therapeutic window and significant pharmacokinetic variability hinder precision dosing. Although CYP3A5-guided strategies have established clinical relevance for tacrolimus initial dose adjustment, they do not fully account for the marked interindividual variability in tacrolimus exposure, highlighting the need for complementary models to decode more complex genetic regulation. This study aimed to identify candidate genetic modulators of tacrolimus metabolism and develop an integrated predictive framework for individualized therapy. METHODS: Using 46 BXD recombinant inbred mouse strains, we characterized transcriptomics and machine learning, and validated key genes. We then constructed a clinical model using data from 168 renal transplant recipients. RESULTS: We identified 19 genomic loci associated with tacrolimus pharmacokinetic traits and supported DBP/CYP2A6 as candidate modulators associated with tacrolimus disposition. The clinical prediction model, incorporating these genes and clinical variables, achieved robust AUROC. CONCLUSIONS: These findings support a polygenic contribution to tacrolimus metabolism and provide an experimental and computational framework for identifying candidate modulators relevant to individualized dosing. The BXD mouse platform offers a systems-genetics approach for mechanistic discovery that may inform future translational studies on tacrolimus precision dosing.

Animals↗

PubMed2026

Genomic and evolutionary basis of parthenogenesis in a disease-vector tick species.

Haemaphysalis longicornis is an important tick species and pathogen vector characterized by the co-circulation of triploid parthenogenetic and diploid bisexual strains. However, the evolutionary basis of parthenogenesis in this species is unclear. Here we report reference-quality, haplotype-resolved genome assemblies of the parthenogenetic strain and two reference-quality genomes of the bisexual strains. Comparative genomic analysis revealed high collinearity between the parthenogenetic and bisexual genomes, with a stable chromosomal architecture maintained among the three haplotypes of the parthenogenetic strain. The parthenogenetic H. longicornis genome exhibited a major expansion in cell cycle-related gene families, including the inhibitor of apoptosis protein (IAP) family, but was characterized by a contraction in other gene families. Population resequencing of 179 individuals revealed two distinct subpopulations, with chromosome 7 harbouring high genetic differentiation and several candidate genes probably associated with parthenogenesis. Functional experiments showed that knockdown of the BIRC5 gene, a member of the IAP family, suppressed oviposition in both strains, with the parthenogenetic strain exhibiting milder adverse effects probably due to a stronger transcriptional response. Overall, our results reveal the genomic and evolutionary features associated with polyploid parthenogenesis in H. longicornis.

Animals↗

PubMed2006

Geode of the femur: an uncommon manifestation potentially reflecting the pathogenesis of rheumatoid arthritis.

Geodes are noted frequently in rheumatoid arthritis (RA), but large geodes of the femur are uncommon. We describe a patient with RA and a large geode in his femur; histological findings were consistent with a rheumatoid nodule and chronically inflamed synovium. We review the literature of large femoral geodes and what this particular manifestation may reflect about the pathogenesis of RA.

Arthritis, Rheumatoid↗

PubMed2006

BDNF increases synapse density in dendrites of developing tectal neurons in vivo.

Neuronal connections are established through a series of developmental events that involve close communication between pre- and postsynaptic neurons. In the visual system, BDNF modulates the development of neuronal connectivity by influencing presynaptic retinal ganglion cell (RGC) axons. Increasing BDNF levels in the optic tectum of Xenopus tadpoles significantly increases both axon arborization and synapse density per axon terminal within a few hours of treatment. Here, we have further explored the mechanisms by which BDNF shapes synaptic connectivity by imaging tectal neurons, the postsynaptic partners of RGCs. Individual neurons were co-labeled with DsRed2 and a GFP-tagged postsynaptic density protein (PSD95-GFP) to visualize dendritic morphology and postsynaptic specializations simultaneously in vivo. Immunoelectron microscopy confirmed that PSD95-GFP predominantly localized to ultrastructurally identified synapses. Time-lapse confocal microscopy of individual, double-labeled neurons revealed a coincident, activity-dependent mechanism of synaptogenesis and axon and dendritic arbor growth, which is differentially modulated by BDNF. Microinjection of BDNF into the optic tectum significantly increased synapse number in tectal neuron dendritic arbors within 24 hours, without significantly influencing arbor morphology. BDNF function-blocking antibodies had opposite effects. The BDNF-elicited increase in synapse number complements the previously observed increase in presynaptic sites on RGC axons. These results, together with the timescale of the response by tectal neurons, suggest that the effects of BDNF on dendritic synaptic connectivity are secondary to its effects on presynaptic RGCs. Thus, BDNF influences synaptic connectivity in multiple ways: it enhances axon arbor complexity expanding the synaptic territory of the axon, while simultaneously coordinating synapse formation and stabilization with individual postsynaptic cells.

Animals↗

PubMed2006

Age-related reexpression of p75 in axotomized motoneurons.

p75 was immunohistochemically identified in spinal motoneurons in immature and adult rats after either distal peripheral axotomy or root avulsion. Few or no p75 positive motoneurons were observed after distal axotomy in animals at the age of postnatal day 1 and postnatal day 7, whereas the injury induced marked neuronal death. Motoneurons reexpressed p75 from the end of the second postnatal week to adulthood in response to distal axotomy, whereas most motoneurons survived after the injury. On the other hand, root avulsion in animals of all ages did not cause significant p75 expression in avulsed motoneurons where most motoneurons died ultimately. The potential role of such reexpression in motoneuron protection is discussed.

Age Factors↗

PubMed2006

[Somatostatin levels and polymorphonuclear neutrophil life in intestinal ischemia reperfusion of macaque].

OBJECTIVE: To investigate the association of somatostatin (SST) levels in plasma or jejunum tissue and polymorphonuclear neutrophil (PMN) life in intestinal ischemia reperfusion of macaque. METHODS: MODS model in macaque was established by clamping superior mesenteric artery. The levels of SST in plasma and jejunum tissue were measured by radioimmunoassay. After incubated with SST, the apoptotic PMN were determined by the morphological studies, flow cytometer and DNA agarose electrophoresis. The expression of SSTR on PMN was detected by biosensor. RESULTS: SST levels in macaque plasma or jejunum tissue were significantly decreased after intestinal ischemia reperfusion (IR) injury. The apoptotic rate of PMN was obviously reduced (15.4% +/- 1.4% to 3.5% +/- 0.5%, P < 0.05). However, the number of apoptotic macrophage from abdominal cavity was clearly increased. The apoptotic rate of PMN was significantly increased (20.0% +/- 2.2% to 50.2% +/- 1.8%, P < 0.01) after incubated with SST in vitro. Specific DNA ladder bands from PMN were visualized with agarose electrophoresis. Specific bindings between PMN and the antibodies for SSTR1 (548 RU/ml +/- 20 RU/ml) or SSTR2 (28 RU/ml +/- 21 RU/ml) were detected. CONCLUSION: The physiological apoptosis of PMN in macaque could be induced by SST through SSTRs on PMN. The decreased SST levels in macaque plasma or jejunum tissue in the state of intestinal ischemia reperfusion might extend PMN life and promote the occurrence of MODS.

Animals↗

PubMed2006

Sonography of the first dorsal metatarsal artery of the foot.

PURPOSE: To describe the gray-scale and Doppler sonographic examination technique and appearances of the first dorsal metatarsal artery (FDMA) of the foot and discuss its clinical significance. METHODS: The dorsal arteries of foot-including the FDMA and the first plantar metatarsal artery-of 374 feet were studied using gray-scale and color Doppler sonography. Due to the difficulty of detecting the FDMA, a majority of them were identified by studying the web area just distal to the intermetatarsal space. The interosseous muscle was identified to determine the classification of the anatomic type of the FDMA. The sonographic results of 152 feet were compared with surgical findings. RESULTS: The average caliber of the FDMA was 1.0 +/- 0.5 mm. The FDMA was classified into 3 groups of variants based on its relationship with the first dorsal interosseous muscle. The groups were identified as the superficial artery (54.5%), intramuscular artery (39.6%), and submuscular artery (9%) variants. The rates of visualization of the distal and proximal portions of the FDMA were 86.6% and 47%, respectively. In the first intermetatarsal space, there were anastomoses between the FDMA and the first plantar metatarsal arteries in 87.6% of the feet. CONCLUSIONS: The FDMA varies greatly; however, sonography can clearly show its morphologic characteristics, such as caliber and location. Sonography also provides valuable preoperative information in microsurgery of the foot.

Adolescent↗

PubMed2006

Endoscopic plication of massively bleeding peptic ulcer by using the Eagle Claw VII device: a feasibility study in a porcine model.

BACKGROUND AND OBJECTIVE: We examined the efficacy of endoscopic plication when using Eagle Claw VII in a porcine bleeding ulcer model. ANIMAL MODEL PREPARATION: The right gastroepiploic artery (diameter 1.5-2 mm) was isolated and was tunneled to small gastrotomies at either the lesser or greater curvature of the stomach. INTERVENTIONS: We applied the Eagle Claw VII to achieve hemostasis. MAIN OUTCOME MEASUREMENTS: The survival of the pigs after endoscopic plication for hemostasis, time to achieve hemostasis with Eagle Claw VII, recurrent bleeding, number of successful plication, and number of suture remained. RESULTS: Endoscopic plication was performed on bleeding gastric ulcers in 6 pigs. The time to achieve hemostasis was 6 minutes 56 seconds +/- 3 minutes 50 seconds. There was no complication. A total of 14 plications were performed. All animals survived for 1 week without recurrent bleeding. At the postmortem, 10 of the plication sutures remained. LIMITATION: Our model cannot simulate the chronicity of peptic ulcer. CONCLUSIONS: In this porcine model, the Eagle Claw VII effectively stopped bleeding from arteries 2 mm in size.

Animals↗

PubMed2006

Tissue engineering of tooth crown, root, and periodontium.

Tissue engineering of teeth requires the coordinated formation of correctly shaped crowns, roots, and periodontal ligament. Previous studies have shown that the dental mesenchyme controls crown morphogenesis and epithelial histogenesis during tooth development in vivo, but little is known about the inductive potential of dissociated mesenchymal cells used in ex vivo cultures. A 2-step method is described in which, by using different types of reassociations between epithelial and mesenchymal tissues and/or cells from mouse embryos, reassociations were cultured in vitro before in vivo implantation. In vitro, the reassociated tissues developed and resulted in tooth-like structures that exhibited normal epithelial histogenesis and allowed the functional differentiation of odontoblasts and ameloblasts. After implantation, the reassociations formed roots and periodontal ligament, the latter connected to developing bone. The shape of the crown, initially suspected to depend on the integrity of the mesenchyme, could be modulated by adjusting the number of dissociated mesenchymal cells reassociated with the epithelial compartment. Based on these results, we propose a refined strategy for tooth tissue engineering that may help to eventually generate morphologically defined teeth.

Animals↗

PubMed2006

Ultrasonic liver discrimination using 2-D phase congruency.

In this paper, we present an experiment to extract liver features using two-dimensional phase congruency, which is invariant to changes in intensity or contrast, to try to avoid the influence of machine settings. The effectiveness of our method was tested on three classes of liver images and shows the potential for physicians to quantify liver pathology in clinical diagnosis.

Adult↗

PubMed2006

[Levels of atrial natriuretic peptide in umbilical cord blood of high risk neonates].

OBJECTIVE: Atrial natriuretic peptide (ANP) is a cardiac hormone with many biological effects. Hypersecretion may lead to hyponatremia. This study examined the umbilical ANP levels in high risk neonates. METHODS: A total of 117 high risk neonates born between June, 2004 and June, 2005 were divided into Simple asphyxia and Normal score groups according to their Apgar's scores. The Simple asphyxia group was subdivided into Mild (n=20) and Severe asphyxia groups (n=17), and the Normal score group was subdivided into Infection (n=25) and Non-infection groups (n=55). Forty normal neonates were used as the Control group. The samples of umbilical cord blood were collected at delivery and the umbilical ANP levels were measured by radioimmunoassay. Meanwhile the sodium levels in the peripheral vein were measured. RESULTS: The mean umbilical ANP levels in high risk neonates were significantly higher than those in the normal neonates. A more significant increase of the umbilical ANP level was observed in premature infants (1.46 +/- 0.39 ng/mL), and neonates with serious infection (1.16 +/- 0.35 ng/mL) and with severe asphyxia (2.12 +/- 0.46 ng/mL) compared with the normal neonates (0.62 +/- 0.33 ng/mL; P < 0.01). The serum sodium level was negatively correlated with the umbilical ANP level (r=-0.99, P < 0.01). CONCLUSIONS: The umbilical ANP levels increased significantly in the high risk neonates, suggesting high risk neonates are susceptible to hyponatremia.

Atrial Natriuretic Factor↗

PubMed2006

[Expression change of TIF3 p36 at different stages of human bronchial epithelial cells transformed and induced by cadmium chloride].

OBJECTIVE: To explore the molecular mechanisms potentially responsible for carcinogenesis due to cadmium by detecting expression change of the translation initiation factor 3 (TIF3 p36) in those malignant transformation of human bronchial epithelial cell lines (16HBE) induced by cadmium chloride (CdCl(2)). METHODS: The expression changes of TIF3 p36 were detected and analyzed at different stages of malignant cells (semi transformed cells, transformed cells and tumorigenic cells) induced by CdCl(2) solution with both reverse transcription PCR technique and sensitive fluorescent quantitative PCR assay. RESULTS: Compared with non-transformed human bronchial epithelial cells, the results of fluorescent quantitative PCR assay showed that the semi-transformed cells, transformed cells and tumorigenic cells all expressed higher levels of TIF3 p36 mRNA (P < 0.01 or P < 0.05). As compared with the control cells, the TIF3 expressions at different stages of malignant transformation were 3.1 times, 5.9 times and 9.9 times higher respectively in the low dosage group of CdCl(2) (5 micromol/L); 7.1 times, 6.8 times and 14.8 times respectively in the middle dosage group of CdCl(2) (10 micromol/L); 3.6 times, 3.0 times and 9.1 times respectively in high of dose of CdCl(2) (15 micromol/L). These results showed that there was the positive correlation between overexpression levels of TIF3 p36 mRNA and the malignant degree of the cells, but they were not related to the dosages of cadmium. CONCLUSION: There is significantly abnormal overexpression of TIF3 gene during malignant transformation of human bronchial epithelial cell line induced by cadmium chloride, and the TIF3 expression is associated with the malignant degree of the cells, which may be one of molecular mechanisms potentially responsible for the carcinogenesis due to cadmium.

Bronchi↗

PubMed2005

Human T lymphocyte responses against lung cancer induced by recombinant truncated mouse EGFR.

The induction of active cellular responses against EGFR should be a promising approach for the treatment of those receptor-positive tumors. However, the immunity against EGFR is presumably difficult to elicit by vaccine based on self or syngeneic EGFR due to the immune tolerance acquired during the development in immune system. We proposed a model to break immune tolerance against self-EGFR through an altered immunogen source based on xenogeneic homologous EGFR. We have previously shown human EGFR as a xenoantigen could induce specific immune responses in mouse and cross-react with mouse EGFR, and resulted in therapeutic benefits for EGFR-positive mouse tumor. Here, we show a recombinant form of extracellular domain of mouse EGFR, in the presence of DCs, could activate human peripheral T cells to proliferate, secret IFN-gamma, the induced responses could cross-react with human EGFR and kill autologous EGFR-positive lung cancer cells which could be blocked by anti-CD8 and anti-MHC class I antibody. There is no detectable cytotoxical activity against lung tissue, liver tissue and kidney tissue derived from paracancerous normal tissue. These observations suggest that antitumor immunity induced by the truncated mouse EGFR may be provoked in a cross-reaction between mouse EGFR and self-EGFR, and may provide insight into treatment of EGFR-positive tumors through induction of the autoimmune responses against EGFR.

Animals↗

PubMed2005

Mesenchymal hamartoma of liver: magnetic resonance imaging and histopathologic correlation.

AIM: To describe the imaging features of hepatic mesenchymal hamartoma with emphasis on magnetic resonance imaging (MRI) compared to histopathologic results. METHODS: Spin-echo sequence(SE),fast spin-echo sequence(FSE) were performed in 12 children (7 males,5 females) with mesenchymal hamartoma of the liver (MHL), aged 1.2 months to 12 years;( mean age, 6.3 years) axial, saggital, coronary plain imaging with an Elscint 2.0T MR equipment. Their main symptoms were abdominal mass (5 cases), enlarged liver (8 cases), abdominal pain (1 case) and anemia (2 cases), and negative alphafetoprotein. Dynamic enhancement examination was added in 2 cases. RESULTS: Six cases had single mass type of MHL, in which 3 cases had solid masses showing slight low-signal-intensity in T1WI, and irregular high-signal-intensity in T2WI, 1 case had a cystic-solid mixed mass showing several border-clear cysts in a solid mass, 2 cases had cystic masses with multi-septa. Five cases had diffuse and multifocal lesions type of MHL with its signal intensity being similar to that of the solid mass. One case had a combined diffuse and single cystic mass. In the early dynamic enhancement examination, the lesions were slightly circum-enhanced , and the center was enhanced in the later scan images. Inner hepatic vessels were compressed in 5 cases, vena cava and abdominal aortae were compressed in 3 cases. Pathological findings included fiber hyperplasia, hyaline degeneration, biliary duct hyperplasia, lobule-like array. CONCLUSION: MR imaging is a better way to differentiate and diagnose MHL. MHL may be recognized by its characteristic occurrence in infancy and MR imaging features.

Child↗

PubMed2005

BDNF stabilizes synapses and maintains the structural complexity of optic axons in vivo.

Brain-derived neurotrophic factor (BDNF) modulates synaptic connectivity by increasing synapse number and by promoting activity-dependent axon arbor growth. Patterned neuronal activity is also thought to influence the morphological maturation of axonal arbors by directly influencing the stability of developing synapses. Here, we used in vivo time-lapse imaging to examine the relationship between synapse stabilization and axon branch stabilization, and to better understand the participation of BDNF in synaptogenesis. Green fluorescent protein (GFP)-tagged synaptobrevin II was used to visualize presynaptic specializations in individual DsRed2-labeled Xenopus retinal axons arborizing in the optic tectum. Neutralizing endogenous tectal BDNF with function-blocking antibodies significantly enhanced GFP-synaptobrevin cluster elimination, a response that was paralleled by enhanced branch elimination. Thus, synapse dismantling was associated with axon branch pruning when endogenous BDNF levels were reduced. To obtain a second measure of the role of BDNF during synapse stabilization, we injected recombinant BDNF in tadpoles with altered glutamate receptor transmission in the optic tectum. Tectal injection of the NMDA receptor antagonists APV or MK801 transiently induced GFP-synaptobrevin cluster dismantling, but did not significantly influence axon branch addition or elimination. BDNF treatment rescued synapses affected by NMDA receptor blockade: BDNF maintained GFP-synaptobrevin cluster density by maintaining their addition rate and rapidly inducing their stabilization. Consequently, BDNF influences synaptic connectivity in multiple ways, promoting not only the morphological maturation of axonal arbors, but also their stabilization, by a mechanism that influences both synapses and axon branches.

Animals↗

PubMed2005

Creation of estrogen resistance in vivo by transgenic overexpression of the heterogeneous nuclear ribonucleoprotein-related estrogen response element binding protein.

Estrogen unresponsiveness among primate species can result from overexpression of a heterogeneous nuclear ribonucleoprotein (hnRNP) that competes with estrogen receptor (ER) for binding to the estrogen-response element (ERE). This hnRNP has been coined the "ERE-binding protein" (ERE-BP). The ERE-BP is a member of the hnRNP C-like subfamily of hnRNPs, traditionally considered to be single-strand RNA binding proteins designed for the stabilization and handling of pre-mRNA. To verify in vivo the dominant-negative actions of the ERE-BP to inhibit ER-ERE-directed transactivation and to avoid the potential for lethality from global overexpression of an hnRNP, we generated transgenic mice that overexpressed ERE-BP in breast tissue under the control of a whey acidic protein gene promoter. Graded overexpression of ERE-BP in transgenic mice was established. Founders were viable and fertile. Female transgenics in all lines gave birth to pups, but their ability to nurse was dependent on the level of ERE-BP expression in breast; high-ERE-BP expressors were unable to lactate. A gradient of impaired breast pheno(histo)type, from near normal to failed ductal development and lactational capacity, correlated with the relative level of transgene expression. ERE-BP, expressed either endogenously as a transgene or after transfection, colocalized with ERalpha in the nucleus of target cells. This work confirms that tissue-targeted overexpression of the ERE-BP can effectively block estrogen-ERalpha-ERE-directed action in vivo.

Animals↗

PubMed2005

A novel site contributing to growth-arrest-specific gene 6 binding to its receptors as revealed by a human monoclonal antibody.

Gas6 (growth-arrest-specific gene 6) is a vitamin K-dependent protein known to activate the Axl family of receptor tyrosine kinases. It is an important regulator of thrombosis and many other biological functions. The C-terminus of Gas6 binds to receptors and consists of two laminin-like globular domains LG1 and LG2. It has been reported that a Ca2+-binding site at the junction of LG1 and LG2 domains and a hydrophobic patch at the LG2 domain are important for receptor binding [Sasaki, Knyazev, Cheburkin, Gohring, Tisi, Ullrich, Timpl and Hohenester (2002) J. Biol. Chem. 277, 44164-44170]. In the present study, we developed a neutralizing human monoclonal antibody, named CNTO300, for Gas6. The antibody was generated by immunization of human IgG-expressing transgenic mice with recombinant human Gas6 protein and the anti-Gas6 IgG sequences were rescued from an unstable hybridoma clone. Binding of Gas6 to its receptors was partially inhibited by the CNTO300 antibody in a dose-dependent manner. To characterize further the interaction between Gas6 and this antibody, the binding kinetics of CNTO300 for recombinant Gas6 were compared with independently expressed LG1 and LG2. The CNTO300 antibody showed comparable binding affinity, yet different dependence on Ca2+, to Gas6 and LG1. No binding to LG2 was detected. In the presence of EDTA, binding of the antibody to Gas6 was disrupted, but no significant effect of EDTA on LG1 binding was evident. Further epitope mapping identified a Gas6 peptide sequence recognized by the CNTO300 antibody. This peptide sequence was found to be located at the LG1 domain distant from the Ca2+-binding site and the hydrophobic patch. Co-interaction of Gas6 with its receptor and CNTO300 antibody was detected by BIAcore analysis, suggesting a second receptor-binding site on the LG1 domain. This hypothesis was further supported by direct binding of Gas6 receptors to an independently expressed LG1 domain. Our results revealed, for the first time, a second binding site for Gas6-receptor interaction.

Amino Acid Sequence↗

PubMed2005

[Ultrasonographic assessment of urethral condyloma acuminatum in men].

OBJECTIVE: To evaluate the value of ultrasonography in diagnosing urethral condyloma acuminatum (CA) in men. METHODS: Twenty-two male patients, aged 36 +/- 19, diagnosed as with urethral CA based on history and clinical symptoms underwent ultrasonography and urethroscopy. The patients were asked to micturate to distend the urethra. The posterior urethra was detected by transrectum approach. Transperineal scans were performed to image the bulbar urethra, scrotal urethra and penile urethra. The sonographically positive results were compared with the pathological results. RESULTS: Eighty-three vegetations were found in the anterior urethra of seventeen patients, and eighty-one vegetations were diagnosed as CA by pathology, of which 1.2% were polyp shape, 38.3% papillary shape, and 60.5% cauliflower mass. Sonourethrography was an accurate predictor of papillary shape and cauliflower mass; however, it was difficult to differentiate between polyp shape vegetation and crystal. CONCLUSION: Sonourethrography is a sensitive and accurate tool not only for primary diagnosis of but also for follow-up of urethral CA in men.

Adolescent↗