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Biomedical subjects

Min Hu

Publications and source records attributed to Min Hu.

At least 19 recordsLinked to original sources

Whole-exome sequencing uncovers the genetic basis of hereditary concomitant exotropia in ten Chinese pedigrees.

PURPOSE: To explore possible pathogenic genes for concomitant exotropia using whole-exome sequencing. METHODS: In this study, 47 individuals from 10 concomitant exotropia (including intermittent exotropia and constant exotropia) pedigrees were enrolled. Whole-exome sequencing was used to screen mutational profiles in 25 affected individuals and 10 unaffected individuals. Sanger sequencing and in silico analysis were performed for all participants. Two target genes were used to capture the sequences of 220 sporadic samples. RESULTS: All 10 concomitant exotropia pedigrees presented autosomal dominant inheritance with childhood onset (3.35 ± 1.51 years old). Eleven different missense variants were identified among seven potential pathogenic genes (COL4A2, SYNE1, LOXHD1, AUTS2, GTDC2, HERC2 and CDH3) that cosegregated with pedigree members. All variants were predicted to be deleterious and had low frequencies in the general population. Distinct variants of COL4A2 were present in three pedigrees, and distinct variants of SYNE1 were present in two pedigrees. Fifteen variants in AUTS2 and four variants in GTDC2 were identified in 220 patients with sporadic concomitant exotropia using a target-capture sequencing approach. CONCLUSION: This is the first study to explore the genetic mechanism of concomitant exotropia and identify seven associated genes (COL4A2, SYNE1, LOXHD1, AUTS2, GTDC2, HERC2 and CDH3) that may be candidate genes causing concomitant exotropia. More samples and in-depth studies are needed to verify these findings.

Adult↗

Apolipoprotein M likely extends its anti-atherogenesis via anti-inflammation.

Apolipoprotein M (apoM), a novel human apolipoprotein recently discovered, predominantly presents in high density lipoprotein (HDL) in plasma, exclusively expressed in liver and in kidney. The present data demonstrated apoM protects against atherosclerosis (AS) primarily via partaking in prebeta-HDL formation and promoting cholesterol efflux to HDL. However, this lipid-metabolism-associated pathway seems unlikely responsible for all atheroprotective effects of apoM. Notably, the human apoM gene is just located in the major histocompatibility complex class III region (MHC-III) on chromosome 6, many genes in this region are related to the immune and inflammatory response. Furthermore, apoM has been documented to link with some inflammatory factors including platelet activating factor (PAF) and leptin. These evidences indicate that apoM may be involved in inflammatory activities in vivo and the potential immuno- and inflam-reactive property of apoM may contribute to the anti-inflammatory function of HDL, as generally acknowledged as an important atheroprotective mechanism of HDL.

Apolipoproteins↗

Localized functional chemical stimulation of TE 671 cells cultured on nanoporous membrane by calcein and acetylcholine.

Acetylcholine sensitive TE 671 cells were cultured on nanoporous membranes and chemically stimulated by localized application of i), calcein-AM and ii), acetylcholine, respectively, onto the bottom face of the membrane employing an ink jet print head. Stimulus correlated response of cells was recorded by fluorescence microscopy with temporal and spatial resolution. Calcein fluorescence develops as a result of intracellular enzymatic conversion of calcein-AM, whereas Ca(2+) imaging using fluo-4 dye was employed to visualize cellular response to acetylcholine stimulation. Using 25 pl droplets and substance concentration ranging from 10 microM to 1 mM on Nucleopore membranes with pore diameters between 50 nm and 1 microm, a resolution on the order of 50 microm was achieved.

Acetylcholine↗

Optical properties of Au-Ag nanoboxes studied by single nanoparticle spectroscopy.

The optical properties of two Au-Ag nanobox samples with average edge lengths of 44 and 58 nm and wall thicknesses of 6 and 8 nm, respectively, have been studied by single particle spectroscopy. The measurements gave an average line width of Gamma = 306 +/- 7 meV with a standard deviation of sigma = 30 meV for the 44-nm boxes, and Gamma = 350 +/- 9 meV with sigma = 35 meV for the 58-nm boxes. These line widths are much broader than those of gold nanorods with comparable resonance energies. The increased broadening is attributed to a combination of surface scattering of electrons, as well as increased radiation damping for the nanoboxes. Discrete dipole approximation calculations have been performed with and without surface scattering of electrons to compare with the experimental spectra. The calculations confirm that both electron-surface scattering and radiation damping are important effects in this system.

Algorithms↗

Nucleotide alterations in the D3 domain of the large subunit of ribosomal DNA among 21 species of equine strongyle.

The expansion segments or divergent (D) domains in the large subunit (LSU) of the ribosomal DNA have been suggested as genetic markers for taxonomic and/or phylogenetic studies of parasites. In the present study, we assessed the degree of sequence variation in the D3 domain and flanking core regions of the LSU for 21 species of equine strongyles (Strongylida: Strongylidae) and determined which positions in the secondary structure of the LSU were associated with the nucleotide alterations. No intraspecific sequence variation was detected in 17 species, for which multiple individual worms were available. Mutations in sequence among species were detected at 19 nucleotide positions, most of which were located in the D3 domain. Fifteen alterations were transitions, three were transversions and one represented a site of multiple mutations. In relation to the secondary structure element of D3, 26% of these mutations were located in unpaired regions (i.e., end of loops, or in bulges of helices) and thus did not appear to alter the pairing arrangement in the helices of the secondary structure. Many of the other mutations represented partial or complete compensatory base pair changes. The magnitude of interspecific nucleotide variation in the D3 domain (0-4%) was considerably less than that recorded for some other nematode groups (enoplids and thelastomatoids), indicating that this region alone is of limited value for taxonomic and phylogenetic studies for strongyles of equids but is interesting in relation to the evolution of ribosomal DNA.

Animals↗

Gold nanostructures: engineering their plasmonic properties for biomedical applications.

The surface plasmon resonance peaks of gold nanostructures can be tuned from the visible to the near infrared region by controlling the shape and structure (solid vs. hollow). In this tutorial review we highlight this concept by comparing four typical examples: nanospheres, nanorods, nanoshells, and nanocages. A combination of this optical tunability with the inertness of gold makes gold nanostructures well suited for various biomedical applications.

Biomedical Engineering↗

Size distribution characteristics of elemental carbon emitted from Chinese vehicles: results of a tunnel study and atmospheric implications.

The size distribution characteristics of elemental carbon (EC) emissions from Chinese vehicles have not been previously described. In this study, we collected size-segregated aerosol samples using a 10-stage MOUDI sampler (0.056-18 microm) in the Zhujiang tunnel, a roadway tunnel in the urban area of Guangzhou, China. The samples were analyzed for EC, organic carbon (OC), and inorganic ions. Fine particles had an OC/EC ratio of 0.57, indicating a dominant contribution of EC from diesel vehicles. Both EC and OC showed a dominant accumulation mode with a mass median aerodynamic diameter (MMAD) of 0.42 microm. In comparison, studies available in the literature typically reported a much lower MMAD for EC (approximately 0.1 microm) in vehicular emissions in North America. A theoretical analysis indicated that the larger EC particles observed in this study could not have resulted from after-emission growth processes (i.e., water accretion, coagulation, and vapor condensation). This leaves operating conditions such as high engine loads and low combustion efficiencies, which are more prevalent in diesel-fueled Chinese vehicles, as a more plausible inherent reason for producing the larger EC agglomerates. While fresh 0.1 microm EC particles are unlikely to act as cloud condensation nuclei (CCN), calculations showed that EC particles as large as 0.42 microm are effective CCN at atmospherically relevant critical supersaturation values of less than 1%. As a result, fresh EC particles from Chinese vehicle emissions could readily undergo cloud processing and form internal mixtures with sulfate in the residue droplet mode particles. This prediction is consistent with observations that EC frequently showed a dominant droplet mode in urban atmospheres in this region. The internal mixing of EC with highly hygroscopic sulfate would facilitate its removal by wet deposition and shorten its lifetime in the atmosphere. In addition, the light-absorbing capabilities of EC particles could also be enhanced due to their internal mixing with sulfate. Numerical aerosol models need to take these factors into consideration for better predictions of the behaviors and effects of urban aerosols in China.

Air Pollutants↗

Prophylaxis against carcinogenesis in three kinds of unestablished tumor models via IL12-gene-engineered MSCs.

Mesenchymal stem cells (MSCs) were adenovirally engineered to secrete interleukin-12 (AdIL-12-MSCs) and evaluated for their anticarcinogenesis efficacy against three kinds of unestablished tumor models including B16 melanoma, LLC Lewis lung cancer and HCC hepatoma. Injection of AdIL-12-MSCs into protected mice before tumor inoculation prevented all of 12 mice in B16 preventive groups, 10 out of 12 in LLC lung cancer model and 11 out of 12 mice in HCC hepatoma model from developing tumors, whereas the control groups pre-receiving PBS were validated for 100% carcinogenesis; the tumor formation rates in free-AdIL-12 and vacant MSC groups were unveiled between approximately 83 and 100% even with plentiful angiogenesis and newborn lymphatic vessels, as well as distant metastases. As a novel approach, AdIL-12-MSC has revealed expected preventive effects on carcinogenesis (P<0.01) with low-toxic, broad-spectrum and long-range superiorities. In conclusion, our data indicate that AdIL-12-MSC possess the potential for tropism to preclinical tumor lesions and deprives surviving or hibernating tumor cells, which have escaped from conventional treatments, of revival and recurrence.

Animals↗

[Needlescopic thoracic sympathectomy for palmar hyperhidrosis].

OBJECTIVE: To evaluate the safety and efficacy of needlescopic thoracic sympathectomy for palmar hyperhidrosis. METHODS: From March 2004 to April 2005, 62 patients, including 23 men and 39 women with a mean age of 23 years (ranged from 12 to 53 years), underwent bilateral needlescopic thoracic sympathectomy. Among all the patients 8 cases had accompanied axillary hyperhidrosis. The degree of palmar sweating was moderate in 16 cases and severe in 46 cases. The sympathetic chain on the body of the second and third ribs in all patients was cauterized and divided; the chain on the fourth rib in those with axillary hyperhidrosis was also severed. Intraoperative changes in palmar temperature and blood flow were recorded. RESULTS: Sympathectomies were successful, and dry limbs were immediately achieved in all patients after surgery. There were no mortality or life-threatening complication, however 1 patient developed moderate pneumothorax which resolved soon after chest drainage. After all procedures, palmar blood perfusion increased significantly and mean palmar temperature elevated by 2.4 degrees C. The mean operative duration was 65 min, and the mean postoperative hospital stay was 1.2 days. No recurrence of palmar hyperhidrosis occurred after a mean follow-up of 6.3 months (ranged from 1 to 13 months). Compensatory sweating was found in 26 patients, but the symptoms were mostly tolerable and required no further treatment. CONCLUSION: Needlescopic thoracic sympathectomy is a safe and effective technique for palmar hyperhidrosis, which is less invasive than conventional video-assisted thoracic surgery.

Adolescent↗

Orphan receptor small heterodimer partner is an important mediator of glucose homeostasis.

The orphan receptor small heterodimer partner (SHP; NROB2) is a transcriptional repressor that inhibits nuclear receptor signaling in diverse metabolic pathways. Here, we report that SHP(-/-) mice exhibited hypoinsulinemia with age, which was associated with increased peripheral insulin sensitivity and increased response of isolated islets to glucose stimulation, yet maintain normal levels of blood glucose. Deficiency in SHP function resulted in up-regulation of glucose transporter 4 mRNA and glucose uptake in muscles, and overexpression of SHP in C2C12 cells inhibited both basal and peroxisomal proliferator-activated receptor gamma (PPARgamma) coactivator-1alpha-stimulated glucose transporter 4 expression and glucose uptake. SHP(-/-) hepatocytes showed markedly decreased basal glucose production in cultures, and SHP(-/-) livers had increased glycogen stores and were more sensitive to insulin inhibition of glucose output, which were concomitant with decreased expression for PPARgamma1, fatty acid translocase, glucose-6-phosphatase, and phosphoenol/pyruvate carboxykinase, and increased mRNAs for glucokinase and pyruvate kinase. In white fat, SHP deficiency resulted in up-regulation of genes involved in insulin sensitizing, including PPARgamma2 and adiponectin. We show that, at the transcriptional level, SHP directly represses adiponectin promoter activity by PPARgamma/liver receptor homolog-1. The results suggest that the increases in insulin sensitivity through multiple signaling pathways in muscle, liver, and fat, with an increase in islet secretory function, represent the complex mechanism whereby SHP deficiency leads to improvement in insulin sensitivity, secretion, and diabetes.

Adipose Tissue, White↗

Estrogens protect pancreatic beta-cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice.

In diabetes, the death of insulin-producing beta-cells by apoptosis leads to insulin deficiency. The lower prevalence of diabetes in females suggests that female sex steroids protect from beta-cell injury. Consistent with this hypothesis, 17beta-estradiol (estradiol) manifests antidiabetic actions in humans and rodents. In addition, estradiol has antiapoptotic actions in cells that are mediated by the estrogen receptor-a (ERalpha), raising the prospect that estradiol antidiabetic function may be due, in part, to a protection of beta-cell apoptosis via ERalpha. To address this question, we have used mice that were rendered estradiol-deficient or estradiol-resistant by targeted disruption of aromatase (ArKO) or ERalpha (alphaERKO) respectively. We show here that in both genders, ArKO(-/-) mice are vulnerable to beta-cell apoptosis and prone to insulin-deficient diabetes after exposure to acute oxidative stress with streptozotocin. In these mice, estradiol treatment rescues streptozotocin-induced beta-cell apoptosis, helps sustain insulin production, and prevents diabetes. In vitro, in mouse pancreatic islets and beta-cells exposed to oxidative stress, estradiol prevents apoptosis and protects insulin secretion. Estradiol protection is partially lost in beta-cells and islets treated with an ERalpha antagonist and in alphaERKO islets. Accordingly, alphaERKO mice are no longer protected by estradiol and display a gender nonspecific susceptibility to oxidative injury, precipitating beta-cell apoptosis and insulin-deficient diabetes. Finally, the predisposition to insulin deficiency can be mimicked in WT mice by pharmacological inhibition of ERalpha by using the antagonist tamoxifen. This study demonstrates that estradiol, acting, at least in part, through ERalpha, protects beta-cells from oxidative injury and prevents diabetes in mice of both genders.

Animals↗

PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling.

TGFbeta signaling controls diverse normal developmental processes and pathogenesis of diseases including cancer and autoimmune and fibrotic diseases. TGFbeta responses are generally mediated through transcriptional functions of Smads. A key step in TGFbeta signaling is ligand-induced phosphorylation of receptor-activated Smads (R-Smads) catalyzed by the TGFbeta type I receptor kinase. However, the potential of Smad dephosphorylation as a regulatory mechanism of TGFbeta signaling and the identity of Smad-specific phosphatases remain elusive. Using a functional genomic approach, we have identified PPM1A/PP2Calpha as a bona fide Smad phosphatase. PPM1A dephosphorylates and promotes nuclear export of TGFbeta-activated Smad2/3. Ectopic expression of PPM1A abolishes TGFbeta-induced antiproliferative and transcriptional responses, whereas depletion of PPM1A enhances TGFbeta signaling in mammalian cells. Smad-antagonizing activity of PPM1A is also observed during Nodal-dependent early embryogenesis in zebrafish. This work demonstrates that PPM1A/PP2Calpha, through dephosphorylation of Smad2/3, plays a critical role in terminating TGFbeta signaling.

Active Transport, Cell Nucleus↗

Foxp3-transduced polyclonal regulatory T cells protect against chronic renal injury from adriamycin.

Chronic proteinuric renal injury is a major cause of ESRD. Adriamycin nephropathy is a murine model of chronic proteinuric renal disease whereby chemical injury is followed by immune and structural changes that mimic human disease. Foxp3 is a gene that induces a regulatory T cell (Treg) phenotype. It was hypothesized that Foxp3-transduced Treg could protect against renal injury in Adriamycin nephropathy. CD4+ T cells were transduced with either a Foxp3-containing retrovirus or a control retrovirus. Foxp3-transduced T cells had a regulatory phenotype by functional and phenotypic assays. Adoptive transfer of Foxp3-transduced T cells protected against renal injury. Urinary protein excretion and serum creatinine were reduced (P<0.05), and there was significantly less glomerulosclerosis, tubular damage, and interstitial infiltrates (P<0.01). It is concluded that Foxp3-transduced Treg cells may have a therapeutic role in protecting against immune injury and disease progression in chronic proteinuric renal disease.

Animals↗

Ultrafast laser studies of the photothermal properties of gold nanocages.

Au nanocages were synthesized via a galvanic replacement reaction. The extinction peak of these hollow structured particles is shifted into the near-IR compared with the Ag nanocube templates. Energy transfer from the Au nanocages into the surrounding environment (water) as well as the coherently excited vibrational modes of the nanocages were studied by femtosecond pump-probe spectroscopy. The time scale for energy relaxation was found to increase with the size of the particles, with the relaxation time being independent of the laser intensity. The time scales for relaxation are comparable to those for solid spherical gold particles and are consistent with energy relaxation being controlled by heat dissipation in the solvent. The period of the coherently excited vibrational mode is proportional to the dimensions of the nanocages. Intensity-dependent measurements show that in solution the nanocages maintain their integrity up to lattice temperatures of 1100 +/- 100 K.

Gold↗

Characteristics of organic matter in PM2.5 in Shanghai.

Solvent extractable organic compounds (SEOC), organic carbon, elemental carbon and water soluble organic carbon (WSOC) in PM(2.5) samples collected in Shanghai, China in 2002 and 2003 were measured to determine the composition and sources of the organic matter in atmospheric aerosols. Distinct seasonal variations were detected with higher concentrations of organic matter in winter. The concentration of total carbon of about 20 microg m(-3) in winter was about three times the summer value. About 30% of the total carbon was water soluble. Unresolved complex mixture (UCM) and fatty acids were the most abundant components quantified in SEOC, similar to other Chinese cities previously studied. High ratio of UCM to n-alkanes (U:R) and the composition of triterpanes indicated that engine exhaust was a major source of the airborne organic matter. Emissions from coal burning had more impact in the rural areas, according to the U:R value and PAHs composition. Chemical mass balance (CMB) modeling shows that about half of the organic carbon was from engine exhaust and about 15% was from coal burning. No clear spatial variation in the concentration of the organic matter was found between urban and rural areas. Our results showed that due to the rapid urbanization and relocation of industrial plants from urban areas to rural areas in the past 20 years, air pollution in rural areas is becoming a serious problem in Shanghai and the Yangtze River delta.

Aerosols↗

Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7: implications for the regulation of the p53-MDM2 pathway.

Herpesvirus-associated ubiquitin-specific protease (HAUSP, also known as USP7), a deubiquitylating enzyme of the ubiquitin-specific processing protease family, specifically deubiquitylates both p53 and MDM2, hence playing an important yet enigmatic role in the p53-MDM2 pathway. Here we demonstrate that both p53 and MDM2 specifically recognize the N-terminal tumor necrosis factor-receptor associated factor (TRAF)-like domain of HAUSP in a mutually exclusive manner. HAUSP preferentially forms a stable HAUSP-MDM2 complex even in the presence of excess p53. The HAUSP-binding elements were mapped to a peptide fragment in the carboxy-terminus of p53 and to a short-peptide region preceding the acidic domain of MDM2. The crystal structures of the HAUSP TRAF-like domain in complex with p53 and MDM2 peptides, determined at 2.3-A and 1.7-A resolutions, respectively, reveal that the MDM2 peptide recognizes the same surface groove in HAUSP as that recognized by p53 but mediates more extensive interactions. Structural comparison led to the identification of a consensus peptide-recognition sequence by HAUSP. These results, together with the structure of a combined substrate-binding-and-deubiquitylation domain of HAUSP, provide important insights into regulation of the p53-MDM2 pathway by HAUSP.

Adaptor Proteins, Signal Transducing↗

Left ventricular bronchogenic cyst.

Bronchogenic cysts occurring in the left ventricle are a medical rarity. One successfully operated case is reported herein. The location of the cyst was just between the epicardium and myocardium of the inferior left ventricular wall, adjacent to the apex of the heart. Complete excision was achieved through a left anterolateral thoracotomy without extracorporeal circulation.

Bronchogenic Cyst↗

Transport distraction osteogenesis using nitinol spring: an exploration in canine mandible.

Some experiments in rabbits have presented the potential feasibility of using shape memory alloy spring for continuous distraction osteogenesis. To confirm the effectiveness of such method, we established canine models for the exploratory experiments of transport distraction osteogenesis using nitinol springs. Simple devices, including an internal 60-mm long sinusoid-shaped nitinol springs were used in the study. All dogs needed only one operation. In the operation, osteotomy was performed to create a 40-mm unilateral segmental mandibular body defect and a tooth-bearing transport bone disc. After reconstructive fixation of the remnant mandible, the spring was constricted and anchored across the distraction gap to activate transport distraction immediately. At the second experimental stage, an ePTFE sheet was further fixed to protect the defect and distraction gap before closing the incision. Control dogs underwent the same operation except for anchoring of the spring to examine the spontaneous bone regeneration. Automatic bone transportation, as a gradual slowdown process, was observed under the effect of the spring. The transport disc could get to the opposite side of the defect, or stopped halfway when ePTFE sheet intervened. Mandibular reconstruction was achieved in all these dogs and better in dogs with sheet protection. No integrated bone mass was found in the defect of control dogs. The study further proves that continuous distraction osteogenesis using nitinol springs is a practical technique, although the devices need more improvement for better control of the process of distraction and the quality of regenerated bone.

Alloys↗