Biomedical subjects

Feng Gao

Publications and source records attributed to Feng Gao.

At least 127 records · Page 7Linked to original sources

PubMed2005

Disruption of P-selectin signaling modulates cell trafficking and results in improved outcomes after mouse warm intestinal ischemia and reperfusion injury.

BACKGROUND: This study analyzes the role of T lymphocytes and neutrophils (PMN) in intestinal ischemia and reperfusion injury (IRI) using either P-selectin blockade or elimination. METHODS: Using a model of severe mouse warm intestinal IRI, the following groups were performed: group 1: wild type C57BL6 no treatment; group 2: wild type treated with r-PSGL1-Ig; group 3: C57BL6 genetically deficient in P-selectin. Survival was assessed at day 7; intestine was assayed for histopathology, apoptosis, myeloperoxidase (MPO), inflammatory cytokines, hemoxygenase-1 (HO-1), and CD3 lymphocytes. Standard statistical comparison was undertaken. RESULTS: The survival was significantly (P < 0.01) improved in the treatment groups: group 1, 50%; group 2, 90%; group 3, 100%. Graded histopathology and crypt apoptosis were improved in groups 2 and 3. MPO and CD3 positive cells were significantly reduced in groups 2 and 3. A significant reduction in inflammatory/Th1-type cytokines was seen in groups 2 and 3 as compared to group 1. Conversely, a significant increase in Th2-type cytokines and HO-1 production was seen selectively in groups 2 and 3. CONCLUSIONS: This study demonstrates the importance of P-selectin signaling in warm, murine intestinal IRI in that either the blockade of or the genetic deficiency in P-selectin confers a survival advantage and reduction in tissue injury/inflammation. The mechanism involves a reduction of PMN and CD3 T cell infiltration and an alteration in the cytokine microenvironment in favor of a Th2 profile. These data implicate T lymphocyte as an important regulatory cell in this inflammatory process.

Animals↗

PubMed2005

[Surgical management for Stanford A aortic dissection].

OBJECTIVE: To summarize the surgical experience for Stanford A aortic dissection. METHODS: Sixty-eight patients with Stanford A aortic dissection underwent surgery from March 1998 to October 2004, acute aortic dissection in 45 cases, chronic aortic dissection in 23 cases. The operation were performed by using moderate hypothermic cardiopulmonary bypass in 53 cases, deep hypothermic circulatory arrest (DHCA) and retrograde cerebral perfusion (RCP) in 11 cases; DHCA with antegrade selective cerebral perfusion (SCP) in 4 cases. Surgical procedures included ascending aortic grafting in 7 cases, ascending and hemiarch grafting in 6, ascending and total arch grafting in 3, ascending and total arch grafting with Frozen elephant trunk procedure in 4. Concomitant procedures included Bentall procedure in 34 cases, Wheat procedure in 12 cases, aortic valvuloplasty in 2 cases, mitral valvuloplasty in 1 cases. Urgent surgery was in 39 cases (emergency surgery in 19). RESULTS: Operative mortality was 7% (urgent surgery mortality was 8%, elective surgery mortality was 7%). Fifty-eight cases were followed up for (37 +/- 22) months. Actuarial survival of 58 cases at 1, 3 and 5 years was 100%, 95% and 86% respectively. CONCLUSION: The choice of surgical procedures depend on the location of intimal tear for Stanford A aortic dissection. Proper surgical indication, technique and brain protections are the key factors of Stanford A aortic dissection surgery.

Adult↗

PubMed2005

Inhibition of iNOS protects the aging heart against beta-adrenergic receptor stimulation-induced cardiac dysfunction and myocardial ischemic injury.

BACKGROUND: beta-adrenergic receptor (AR) and aging are two major contributors to pathogenesis of perioperative myocardial ischemia and infarction. This study compared the response to beta-AR stimulation in the young and aging heart and examined the role of inducible nitric oxide synthase (iNOS) in aging related myocardial ischemic injury and its relation to beta-AR stimulation. MATERIAL AND METHODS: Isolated perfused hearts from young (3-5 months) and aging (24-25 months) rats were subjected to 60 min of 50% coronary flow reduction and 30 min of isoproterenol (Iso) stimulation starting at 30 min of ischemia. The rats were randomized to receive vehicle or 1400W (a selective iNOS inhibitor) at 24 h (2 mg/kg, i.p.) and 1 h (1 mg/kg, i.p.) pre-ischemia. RESULTS: The 30 min of myocardial ischemia resulted in cardiac dysfunction as indicated by a 13 to 45% of reduction in left ventricular developed pressure (LVDP) and +/- dp/dtmax in either young or aging rats. Infusion of Iso for 30 min caused a partial recovery of cardiac function in hearts from young animals receiving either vehicle or 1400W as evidenced by improvements in LVDP and +/- dp/dtmax. In striking contrast, Iso infusion to hearts from aging animals receiving vehicle not only failed to improve ischemia-induced cardiac depression but worsened cardiac function as indicated by a 43 to 60% further reduction in LVDP and +/- dp/dtmax at the end of 30-min Iso infusion, which was also associated with a significant increase in myocardial NO production, ONOO- formation, caspase-3 activation and creatine kinase (CK) release. However, the treatment with a selective iNOS inhibitor-1400W blocked NO production and ONOO- formation, attenuated caspase-3 activation and CK release, and improved LV function in the aging heart, demonstrating a critical link between iNOS generated NO production and aging myocardial ischemic injury. A significant increase of iNOS protein expression, activity and immunoreactivity was found in the baseline aging LV tissues versus their young counterparts. CONCLUSIONS: Aging induces phenotypic up-regulation of iNOS in the heart, in which beta-AR stimulation interacts with ischemia and triggers a markedly increased NO production, which creates a nitrative stress, generates toxic peroxynitrite, activates apoptosis, and eventually causes cardiac dysfunction and myocardial injury. An iNOS inhibitor-1400W can markedly attenuate these adverse effects in the aging heart.

Adrenergic beta-Agonists↗

PubMed2005

[Surgical treatment of the aortic root aneurysm related to Marfan syndrome].

OBJECTIVE: To review the experience of surgical treatment of aortic root aneurysm of Marfan syndrome. METHODS: We The clinical data of 84 Marfan syndrome patients, 61 males and 23 females, aged 35 +/- 12 (5 - 62), 41 cases presenting with aortic dissection (Debakey type I in 32 cases and type II in 9), 52 cases with moderate to severe aortic regurgitation, and 9 cases with moderate to severe mitral regurgitation, 43 cases with cardiac function of class I - II, 30 with class III and 11 with class IV according the New York Heart Association (NYHA) standard, who underwent surgical treatment for aortic root aneurysm with a mean diameter of 68 mm +/- 14 mm, were analyzed. Bentall procedure was performed in 68 cases, Wheat procedure in 6, Cabrol procedure in 5, and aortic valve replacement and aortoplasty in 5. Concomitant procedures included mitral value replacement and mitral valvuoplasty in 3 cases respectively. Urgent surgery was conducted in 28 cases, and elective operation in 56 cases. RESULTS: There were 3 in-hospital deaths (3.57%). 76 cases were followed up for a mean duration of 55 +/- 31 months. Three patients underwent reoperation. The cardiac function returned to class I - II except for 2 cases that remained at the class III. CONCLUSION: Bentall procedure should be the first choice of the surgery for aortic root aneurysm of Marfan syndrome with a low mortality and a good late outcome.

Adolescent↗

PubMed2005

[Left atrial plication for left atrium associated with mitral valve disease].

OBJECTIVE: To evaluate the effects of left atrial plication (LAP) in patients with giant left atrium (GLA) associated with mitral valve disease. METHODS: Twenty-three patients with left atrial diameter (LAD) over 8.0 cm were enrolled. All cases underwent valve replacement and LAP between November 1993 and November 2004 were studied retrospectively. According to New York Heart Association (NYHA) classification, 15 belonged to class III, 8 to class IV. Mitral valve replacements were performed in 18 patients (mechanical valve in 17 and biological valve in 1), double value replacement in 5, tricuspid valve plasty (TVP) in 15, atrial fibrillation radiofrequency ablation in 2. RESULTS: Low output syndrome happened in 3, respiratory failure in 2. The early death was in 3 cases (operative mortality 13%). The causes of death were: heart failure in 2 cases and stroke in 1. LAD was decreased significantly in patients after operation. CONCLUSIONS: LAP has considerably beneficial effects on improvement of postoperative respiratory and cardiac function, reducing operative mortality. Atrial fibrillation radiofrequency ablation is effective in patients with GLA associated with valve disease. It may be recommended for patients with GLA during mitral valve surgery, especially for patients with LAD > 8.0 cm.

Adult↗

PubMed2005

A green chemical approach to the synthesis of tellurium nanowires.

Starch, an economical and safe carbohydrate, has been found to be not only an effective reducing agent but also a new morphology-directing agent for the synthesis of tellurium nanowires using commercial H2TeO4 precursor. The obtained tellurium nanowires are of single-crystal in nature, with an average diameter of approximately 25 nm and length up to 10 microm. A possible synthetic mechanism involves the chain-shaped bioorganic molecule acting as a template for the one-dimensional growth of inorganic tellurium. The effects of different chain-shaped structures and concentrations of biomolecules on the nanowire morphology have been investigated and different one-dimensional structures, including thick rods, short nanowires, bunched nanowires, and assembled spikelet structures, have been fabricated. These experimental results have been found to be useful in substantiating the proposed synthetic mechanism.

Journal Article↗

PubMed2005

The CD154-CD40 T-cell co-stimulation pathway in liver ischemia and reperfusion inflammatory responses.

BACKGROUND: Ischemia-reperfusion (I/R) injury is a prime antigen-independent inflammatory factor in the dysfunction of liver transplants. The precise contribution of T cells in the mechanism of I/R injury remains to be elucidated. As the CD154-CD40 co-stimulation pathway provides essential second signal in the initiation and maintenance of T-cell-dependent immune responses, this study was designed to assess the role of CD154 signaling in the pathophysiology of liver I/R injury. METHODS: A mouse model of partial 90-min warm hepatic ischemia followed by 6 hr of reperfusion was used. Three animal groups were studied: (1) wild-type (WT) mice treated with Ad-(-gal versus Ad-CD40 immunoglobulin; (2) untreated WT versus CD154 (MR1) monoclonal antibody-treated WT mice; and (3) untreated WT versus CD154 knockout mice. RESULTS: The disruption of CD154 signaling in all three animal groups ameliorated otherwise fulminant liver injury, as evidenced by depressed serum glutamic oxaloacetic transaminase levels, compared with controls. These beneficial effects were accompanied by depressed hepatic T-cell sequestration, local decrease of vascular endothelial growth factor expression, inhibition of tumor necrosis factor-(and T-helper type 1 cytokine production, and induction of antiapoptotic (Bcl-2/Bcl-xl) but depression of proapoptotic (caspase-3) proteins. CONCLUSIONS: By using in parallel a gene therapy approach, pharmacologic blockade, and genetically targeted mice, these findings document the benefits of disrupting CD154 to selectively modulate inflammatory responses in liver I/R injury. This study reinforces the key role of CD154-CD40 T-cell co-stimulation in the pathophysiology of liver I/R injury.

Animals↗

PubMed2005

Dendrimer modified magnetite nanoparticles for protein immobilization.

A cascading polyamidoamine (PAMAM) dendrimer was synthesized on the surface of magnetite nanoparticles to allow enhanced immobilization of bovine serum albumin (BSA). Characterization of the synthesis revealed exponential doubling of the surface amine from generations one through four starting with an amino silane initiator. Furthermore, transmission electron microscopy (TEM) revealed clear dispersion of the dendrimer-modified magnetite nanoparticles in methanol solution. The dendrimer-modified magnetite nanoparticles were used to carry out magnetic immobilization of BSA. BSA immobilizing efficiency increased with increasing generation from one to five and BSA binding amount of magnetite nanoparticles modified with G5 dendrimer was 7.7 times as much as that of magnetite nanoparticles modified with only aminosilane. There are two major factors that improve the BSA binding capacity of dendrimer-modified magnetite nanoparticles: one is that the increased surface amine can be conjugated to BSA by a chemical bond through glutaraldehyde; the other is that the available area has increased due to the repulsion of surface positive charge.

Dendrimers↗

PubMed2005

Time-resolved diffuse optical tomographic imaging for the provision of both anatomical and functional information about biological tissue.

We present in vivo images of near-infrared (NIR) diffuse optical tomography (DOT) of human lower legs and forearm to validate the dual functions of a time-resolved (TR) NIR DOT in clinical diagnosis, i.e., to provide anatomical and functional information simultaneously. The NIR DOT system is composed of time-correlated single-photon-counting channels, and the image reconstruction algorithm is based on the modified generalized pulsed spectral technique, which effectively incorporates the TR data with reasonable computation time. The reconstructed scattering images of both the lower legs and the forearm revealed their anatomies, in which the bones were clearly distinguished from the muscles. In the absorption images, some of the blood vessels were observable. In the functional imaging, a subject was requested to do handgripping exercise to stimulate physiological changes in the forearm tissue. The images of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentration changes in the forearm were obtained from the differential images of the absorption at three wavelengths between the exercise and the rest states, which were reconstructed with a differential imaging scheme. These images showed increases in both blood volume and oxyhemoglobin concentration in the arteries and simultaneously showed hypoxia in the corresponding muscles. All the results have demonstrated the capability of TR NIR DOT by reconstruction of the absolute images of the scattering and the absorption with a high spatial resolution that finally provided both the anatomical and functional information inside bulky biological tissues.

Algorithms↗

PubMed2005

Ancient co-speciation of simian foamy viruses and primates.

Although parasite-host co-speciation is a long-held hypothesis, convincing evidence for long-term co-speciation remains elusive, largely because of small numbers of hosts and parasites studied and uncertainty over rates of evolutionary change. Co-speciation is especially rare in RNA viruses, in which cross-species transfer is the dominant mode of evolution. Simian foamy viruses (SFVs) are ubiquitous, non-pathogenic retroviruses that infect all primates. Here we test the co-speciation hypothesis in SFVs and their primate hosts by comparing the phylogenies of SFV polymerase and mitochondrial cytochrome oxidase subunit II from African and Asian monkeys and apes. The phylogenetic trees were remarkably congruent in both branching order and divergence times, strongly supporting co-speciation. Molecular clock calibrations revealed an extremely low rate of SFV evolution, 1.7 x 10(-8) substitutions per site per year, making it the slowest-evolving RNA virus documented so far. These results indicate that SFVs might have co-speciated with Old World primates for at least 30 million years, making them the oldest known vertebrate RNA viruses.

Animals↗

PubMed2005

Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection.

Worldwide HIV-1 vaccine efforts are guided by the principle that HIV-specific T cell responses may provide protection from infection or delay overt disease. However, no clear correlates of T cell-mediated immune protection have been identified. Here, we examine in a HLA-B27(+) HIV seronegative vaccinee persistent HIV-specific vaccine-induced anti-Gag CD4(+) and CD8(+) T cell responses. Although these responses exhibited those characteristics (multifunctionality, appropriate memory phenotype, and targeting of epitopes associated with long-term nonprogression) predicted to correlate with protection from infection, the subject became HIV infected. After HIV infection, the vaccine-induced CD8(+) T cells expanded, but both CD4(+) and CD8(+) T cell responses acquired the functional and phenotypic patterns characteristic of chronic HIV infection. The virus quickly escaped the vaccine-induced T cell response, and the subject progressed more rapidly than expected for someone expressing the HLA-B27 allele. These data suggest that control of HIV by vaccine-elicited HIV-specific T cell responses may be difficult, even when the T cell response has those characteristics predicted to provide optimal protection.

AIDS Vaccines↗

PubMed2005

Crystallization and preliminary X-ray structural studies of a high-affinity CD8alphaalpha co-receptor to pMHC.

The class I CD8 positive T-cell response is involved in a number of conditions in which artificial down-regulation and control would be therapeutically beneficial. Such conditions include a number of autoimmune diseases and graft rejection in transplant patients. Although the CD8 T-cell response is dominated by the TCR-pMHC interaction, activation of T cells is in most cases also dependent on a number of associated signalling molecules. Previous work has demonstrated the ability of one such molecule (CD8) to act as an antagonist to T-cell activation if added in soluble form. Therefore, a high-affinity mutant CD8 (haCD8) has been developed with the aim of developing a therapeutic immunosuppressor. In order to fully understand the nature of the haCD8 interaction, this protein was crystallized using the sitting-drop vapour-diffusion method. Single haCD8 crystals were cryocooled and used for data collection. These crystals belonged to space group P6(4)22 (assumed by similarity to the wild type), with unit-cell parameters a = 101.08, c = 56.54 A. VM calculations indicated one molecule per asymmetric unit. A 2 A data set was collected and the structure is currently being determined using molecular replacement.

CD8-Positive T-Lymphocytes↗

PubMed2005

Mechanical traumatic injury without circulatory shock causes cardiomyocyte apoptosis: role of reactive nitrogen and reactive oxygen species.

Apoptotic cell death plays a critical role in tissue injury and organ dysfunction under a variety of pathological conditions. The present study was designed to determine whether apoptosis may contribute to posttraumatic cardiac dysfunction, and if so, to investigate the mechanisms involved. Male adult mice were subjected to nonlethal traumatic injury, and cardiomyocyte apoptosis, cardiac function, and cardiac production of reactive oxygen/nitrogen species were determined. Modified Noble-Collip drum trauma did not result in circulatory shock, and the 24-h survival rate was 100%. No direct mechanical traumatic injury was observed in the heart immediately after trauma. However, cardiomyocyte apoptosis gradually increased and reached a maximal level 12 h after trauma. Significantly, cardiac dysfunction was observed 24 h after trauma in the isolated perfused heart. This was completely reversed when apoptosis was blocked by administration of a nonselective caspase inhibitor immediately after trauma. In the traumatized hearts, reactive nitrogen species (e.g., nitric oxide) and reactive oxygen species (e.g., superoxide) were both significantly increased, and maximal nitric oxide production preceded maximal apoptosis. Moreover, a highly cytotoxic reactive species, peroxynitrite, was markedly increased in the traumatic heart, and there was a significant positive correlation between cardiac nitrotyrosine content and caspase 3 activity. Our present study demonstrated for the first time that nonlethal traumatic injury caused delayed cell death and that apoptotic cardiomyocyte death contributes to posttrauma organ dysfunction. Antiapoptotic treatments, such as blockade of reactive nitrogen oxygen species generation, may be novel strategies in reducing posttrauma multiple organ failure.

Animals↗

PubMed2005

CD62 blockade with P-Selectin glycoprotein ligand-immunoglobulin fusion protein reduces ischemia-reperfusion injury after rat intestinal transplantation.

BACKGROUND: Intestinal transplantation (ITx) is severely limited by ischemia-reperfusion (I/R) injury. This study investigates I/R injury and ameliorates its consequences by using a recombinant protein targeted against selectins (recombinant P-selectin glycoprotein ligand-immunoglobulin [rPSGL-Ig]). METHODS: An isogeneic model of ITx was undertaken with control animals (no therapy) and treatment animals (rPSGL-Ig). Survival was assessed. Separate groups underwent an analysis examining tissue at multiple time points after I/R injury including histopathology; myeloperoxidase staining; immunostaining for CD3 and ED2; polymerase chain reaction analysis of interleukin (IL)-8/cytokine-inducible neutrophil chemoattractant, IL1beta, IL-6, interferon-gamma, IL-2, IL-4, and IL10; and western blots for hemoxygenase-1, BCL-2, and BCL-xl. Standard statistical analysis was undertaken. RESULTS: Treatment with rPSGL-Ig resulted in significantly improved survival after ITx. Analysis demonstrated diminished injury on histopathology and reduced tissue infiltration of neutrophils and lymphocytes. Significant differences in the cytokine profile after ITx were seen between the two groups including the production of inflammatory cytokines at 24 hr and the Th1 and Th2 cytokines at 2 and 4 hr. Last, treatment resulted in increased production of hemoxygenase, BCL-2, and BCL-xl. CONCLUSION: The results of this investigation of I/R injury after ITx revealed that rPSGL-Ig treatment led to marked improvement in outcome. The mechanism of action seems to involve the blockade of neutrophil and lymphocyte infiltration leading to a decreased inflammatory response possibly driven by Th2 cytokines. The results not only lend insight into the mechanisms behind I/R injury after ITx but also demonstrate a potential therapeutic modality to ameliorate its consequences.

Animals↗

PubMed2005

Cervical carcinoma in the elderly: an analysis of patterns of care and outcome.

BACKGROUND: Advanced age often is considered a poor prognostic factor for cervical carcinoma. The authors investigated the patterns of care and treatment outcomes of elderly women with cervical carcinoma. METHODS: A hospital-based tumor registry was used to identify patients with invasive cervical carcinoma who were treated between 1986 and 2003. Patients were divided into 2 cohorts: women age < 70 years and women age > or = 70 years. Survival was examined using the Kaplan-Meier method. Single and multivariate Cox proportional hazards modeling was used to estimate hazard ratios with 95% confidence intervals (95% CI). RESULTS: In total, 1582 patients were identified, including 1385 patients age < 70 years and 197 patients age > or = 70 years. The elderly patients presented with more advanced stage tumors at diagnosis (P <0.0001) and were more likely to have nonsquamous neoplasms (P=0.002). A marked difference in treatment was noted for the elderly cohort, even after stratifying by disease stage. Only 16% of the older patients underwent surgical treatment compared with 54% of the younger patients (P <0.0001). Elderly women were 9 times more likely to receive no treatment (P <0.0001). In a multivariate model of known prognostic factors, the hazard ratio for death from any cause in women age > 70 years was 2.1 (95% CI, 1.5-3.0). The hazard ratio for death from cervical carcinoma in the elderly women was 1.6 (95% CI, 1.1-2.5). CONCLUSIONS: Age is an important factor in the allocation of treatment and survival for patients with cervical carcinoma. Elderly women with cervical carcinoma are more likely to receive primary radiotherapy, to forego treatment, and to die from their disease.

Adult↗

PubMed2005

Simple strategies for reducing sample loads in in vitro metabolic stability high-throughput screening experiments: a comparison between traditional, two-time-point and pooled sample analyses.

Higher-throughput ADME programs in early drug discovery are becoming common throughout the pharmaceutical industry as companies strive to reduce their compound attrition in later-stage development. Many of the ADME assays developed into higher-throughput formats rely on LC/MS analyses. Since the biological aspects of the assay are amenable to parallel processes using dense plate formats, the number of samples generated from these assays produce a large analysis load for serial LC/MS. Presented in this report are two novel strategies, including a sample pooling method and a two time-point method, that could be used in drug discovery to reduce the number of samples generated during multiple time-point in-vitro ADME assays. One hundred and sixty-three compounds were subjected to human microsomal incubations with full time-point method samples taken at t = 0, 5, 15, 30, and 45 min. The ER data correlation (R(2)) between the full time-point method and the pooling method and two time-point methods were 0.98 and 0.97, respectively. Both methods have the potential to: 1. produce data of similar quality to traditional high throughput ADME assays, 2. be easily implemented, 3. shorten analytical run times, and 4. be reproducible and robust.

Algorithms↗

PubMed2005

Inflammatory responses in a new mouse model of prolonged hepatic cold ischemia followed by arterialized orthotopic liver transplantation.

The current models of liver ischemia/reperfusion injury (IRI) in mice are largely limited to a warm ischemic component. To investigate the mechanism of hepatic "cold" IRI, we developed and validated a new mouse model of prolonged cold preservation followed by syngeneic orthotopic liver transplantation (OLT). Two hundred and forty-three OLTs with or without rearterialization and preservation in University of Wisconsin solution at 4 degrees C were performed in Balb/c mice. The 14-day survivals in the nonarterialized OLT groups were 92% (11/12), 82% (9/11), and 8% (1/12) after 1-hour, 6-hour and 24-hour preservation, respectively. In contrast, hepatic artery reconstruction after 1-hour, 6-hour, and 24-hour preservation improved the outcome as evidenced by 2-week survival of 100% (12/12), 100% (10/10), and 33% (4/12), respectively, and diminished hepatocellular damage (serum alanine aminotransferase /histology). Moreover, 24-hour (but not 1-h) cold preservation of rearterialized OLTs increased hepatic CD4+ T-cell infiltration and proinflammatory cytokine (tumor necrosis factor-alpha, interleukin 2, interferon-gamma) production, as well as enhanced local apoptosis, and Toll-like receptor 4/caspase 3 expression. These cardinal features of hepatic IRI validate the model. In conclusion, we have developed and validated a new mouse model of IRI in which hepatic artery reconstruction was mandatory for long-term animal survival after prolonged (24-h) OLT preservation. With the availability of genetically manipulated mouse strains, this model should provide important insights into the mechanism of antigen-independent hepatic IRI and help design much needed refined therapeutic means to combat hepatic IRI in the clinics.

Adenosine↗

PubMed2005

Hypoxia-induced alterations in hyaluronan and hyaluronidase.

Hyaluronan (HA), a large negatively-charged polysaccharide, is a major component of vessel basal membrane. HA is expressed by a variety of cells, including tumor and endothelial cells. We hypothesized that HA could be up-regulated by hypoxia to enhance vessel formation. To determine the effect of hypoxia on the production of HA, tumor cells were treated with either media alone (control) or a hypoxia inducer (CoCl or NaN3) for 24 h. The level of HA in the media was then measured by ELISA. The results showed that both CoCl and NaN3 induced the production of HA. Since the low molecular weight form of HA (SMW) possesses pro-angiogenic properties, we investigated whether hypoxia-induced HA can be processed into SMW. Under hypoxic conditions, the activity of hyaluronidase, the enzyme responsible for degrading HA, was measured by an ELISA-like assay. The activity of hyaluronidase was shown to be up-regulated by hypoxia and, further, could carry out the function of processing HA into SMW. In addition, the hypoxic areas of tumor tissues were stained strongly with biotinylated HA-binding proteins, indicating that the level of HA was high compared to the oxic areas. This study demonstrates that hypoxia can stimulate the production of HA and the activity of hyaluronidase, which may promote angiogenesis as a compensation mechanism for hypoxia.

Acetylglucosaminidase↗