Biomedical subjects

Ying Chen

Publications and source records attributed to Ying Chen.

At least 109 records · Page 6Linked to original sources

PubMed2005

Interactions between CAP70 and actinfilin are important for integrity of actin cytoskeleton structures in neurons.

The integrity of dynamic actin structures is coupled to a variety of neurological processes. Actin-binding proteins play a critical role in regulating actin structure dynamics. A link between actin-binding proteins and receptor interacting scaffolding proteins may provide a conduit for transmitting signaling events to the cytoskeleton. Actinfilin is a brain-enriched actin-binding protein, though its functions are currently unknown. We report here that actinfilin interacts with the multi-PDZ domain protein CAP70. Recombinant expression of an actin-binding domain of actinfilin progressively causes marked changes of cellular morphology. The effect on cell morphology may be reduced by co-expression with CAP70. Mutation of actinfilin lacking the ability to interact with CAP70 abolished the effect by CAP70. The evidence suggests a role of actinfilin and possible regulation by scaffolding proteins.

Actins↗

PubMed2005

ER-associated protein degradation is a common mechanism underpinning numerous monogenic diseases including Robinow syndrome.

Correct folding of nascent polypeptide chains within the ER is critical for function, assembly into multi-subunit complexes and trafficking through the exocytic pathway for secretory and cell surface proteins. This process is rather inefficient, and a substantial proportion of nascent polypeptides is rejected by an ER quality control system and targeted for degradation. In some cases, only a minor fraction of nascent chains is correctly folded, and the smallest alteration to polypeptide primary structure (i.e. point mutation) can result in the complete loss of function with inherent pathological consequences; cystic fibrosis and emphysema result from such mutations. We have taken a bioinformatic approach to parse a large database of known disease susceptibility genes for candidates whose disease-associated alleles are likely prone to misfolding in the ER. Surprisingly, we find that proteins with ER-targeting signals are over represented in this database when compared with all predicted proteins in the human genome (45 versus 30%). We selected a subgroup of proteins that were positive for both an ER-targeting signal and a membrane-anchoring domain and thereby identified several ER-associated degradation diseases candidates. To determine whether our analysis had identified new ER-degradation substrates, we established that ER retention is indeed the mechanism underlying Robinow syndrome (RRS), one of the identified candidates. Specifically, mutant alleles of ROR2 that are associated with RRS are retained within the ER, whereas wild-type and non-pathogenic alleles are exported to the plasma membrane. These data both uncover a major pathogenic factor for RRS and indicate that misfolding of secretory proteins is likely to significantly contribute to human disease and morbidity.

Abnormalities, Multiple↗

PubMed2005

A local mechanism mediates NAD-dependent protection of axon degeneration.

Axon degeneration occurs frequently in neurodegenerative diseases and peripheral neuropathies. Important insight into the mechanisms of axon degeneration arose from findings that the degeneration of transected axons is delayed in Wallerian degeneration slow (Wlds) mice with the overexpression of a fusion protein with the nicotinamide adenine dinucleotide (NAD) synthetic enzyme, nicotinamide mononucleotide adenylyltransferase (Nmnat1). Although both Wld(s) and Nmnat1 themselves are functional in preventing axon degeneration in neuronal cultures, the underlying mechanism for Nmnat1- and NAD-mediated axon protection remains largely unclear. We demonstrate that NAD levels decrease in degenerating axons and that preventing this axonal NAD decline efficiently protects axons from degeneration. In support of a local protective mechanism, we show that the degeneration of axonal segments that have been separated from their soma could be prevented by the exogenous application of NAD or its precursor nicotinamide. Furthermore, we provide evidence that such Nmnat1/NAD-mediated protection is primarily mediated by their effects on local bioenergetics. Together, our results suggest a novel molecular pathway for axon degeneration.

Adenosine Triphosphate↗

PubMed2005

Shape controlled growth of gold nanoparticles by a solution synthesis.

The shape of gold nanoparticles has been successfully tuned among penta-twinned decahedrons, truncated tetrahedrons, cubes, octahedrons, hexagonal thin plates by introducing a small amount of salt into a N,N-dimethylformamide (DMF) solution containing poly(vinyl pyrrolidone) (PVP), and changing the temperature or the concentration of the gold precursor.

Journal Article↗

PubMed2005

Butylhydroquinone protects cells genetically deficient in glutathione biosynthesis from arsenite-induced apoptosis without significantly changing their prooxidant status.

Arsenic, first among the top environmentally hazardous substances, is associated with skin, lung, liver, kidney, prostate, and bladder cancer. Arsenic is also a cardiovascular and a central nervous system toxicant, and it has genotoxic and immunotoxic effects. Paradoxically, arsenic trioxide is used successfully in the treatment of acute promyelocytic leukemia and multiple myeloma. Arsenic induces oxidative stress, and its toxicity is decreased by free thiols and increased by glutathione depletion. To further characterize the role of glutathione and oxidative stress in the toxicity of arsenic, we have used fetal fibroblasts from Gclm(-/-) mice, which lack the modifier subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione biosynthesis. Gclm(-/-) mouse embryo fibroblasts (MEFs) are eight times more sensitive to arsenite-induced apoptotic death. Because of a dramatic decrease in glutathione levels, Gclm(-/-) MEFs have a high prooxidant status that is not significantly relieved by treatment with the phenolic antioxidant tBHQ; however, tBHQ blocks arsenite-induced apoptosis in both Gclm(+/+) and Gclm(-/-) cells, although it raises a significant antioxidant response only in Gclm(+/+) cells. Global gene expression profiles indicate that tBHQ is significantly effective in reversing arsenite-induced gene deregulation in Gclm(+/+) but not in Gclm(-/-) MEFs. This effect of tBHQ is evident in the expression of metalloproteases and chaperones, and in the expression of genes involved in DNA damage and repair, protein biosynthesis, cell growth and maintenance, apoptosis, and cell cycle regulation. These results suggest that regulation of glutathione levels by GCLM determines the sensitivity to arsenic-induced apoptosis by setting the overall ability of the cells to mount an effective antioxidant response.

Animals↗

PubMed2005

Expression of cytochrome p450 and other biotransformation genes in fetal and adult human nasal mucosa.

Despite recent progress in the identification and characterization of numerous nasal biotransformation enzymes in laboratory animals, the expression of biotransformation genes in human nasal mucosa remains difficult to study. Given the potential role of nasal biotransformation enzymes in the metabolism of airborne chemicals, including fragrance compounds and therapeutic agents, as well as the potential interspecies differences between laboratory animals and humans, it would be highly desirable to identify those biotransformation genes that are expressed in human nasal mucosa. In this study, a global gene expression analysis was performed to compare biotransformation enzymes expressed in human fetal and adult nasal mucosa to those expressed in liver. The identities of a list of biotransformation genes with apparently nasal mucosa-selective expression were subsequently confirmed by RNA-polymerase chain reaction (PCR) and DNA sequencing of the PCR products. Further quantitative RNA-PCR experiments indicated that, in the fetus, aldehyde dehydrogenase 6 (ALDH6), CYP1B1, CYP2F1, CYP4B1, and UDP glucuronosyltransferase 2A1 are expressed preferentially in the nasal mucosa and that ALDH7, flavin-containing monooxygenase 1, and glutathione S-transferase P1 are at least as abundant in the nasal mucosa as in the liver. The nasal mucosal expression of CYP2E1 was also detected. These findings provide a basis for further explorations of the metabolic capacity of the human nasal mucosa for xenobiotic compounds.

Adult↗

PubMed2005

Spatiotemporal analysis of exocytosis in mouse parotid acinar cells.

Exocrine cells of the digestive system are specialized to secrete protein and fluid in response to neuronal and/or hormonal input. Although morphologically similar, parotid and pancreatic acinar cells exhibit important functional divergence in Ca(2+) signaling properties. To address whether there are fundamental differences in exocytotic release of digestive enzyme from exocrine cells of salivary gland versus pancreas, we applied electrophysiological and optical methods to investigate spatial and temporal characteristics of zymogen-containing secretory granule fusion at the single-acinar cell level by direct or agonist-induced Ca(2+) and cAMP elevation. Temporally resolved membrane capacitance measurements revealed that two apparent phases of exocytosis were induced by Ca(2+) elevation: a rapidly activated initial phase that could not be resolved as individual fusion events and a second phase that was activated after a delay, increased in a staircaselike fashion, was augmented by cAMP elevation, and likely reflected both sequential compound and multivesicular fusion of zymogen-containing granules. Optical measurements of exocytosis with time-differential imaging analysis revealed that zymogen granule fusion was induced after a minimum delay of approximately 200 ms, occurred initially at apical and basolateral borders of acinar cells, and under strong stimulation proceeded from apical pole to deeper regions of the cell interior. Zymogen granule fusions appeared to coordinate subsequent fusions and produced persistent structures that generally lasted several minutes. In addition, parotid gland slices were used to assess secretory dynamics in a more physiological context. Parotid acinar cells were shown to exhibit both similar and divergent properties compared with the better-studied pancreatic acinar cell regarding spatial organization and kinetics of exocytotic fusion of zymogen granules.

Animals↗

PubMed2005

Multiscale multifractality analysis of a 12-lead electrocardiogram.

This paper proposes that a multiscale multifractality (MSMF) method be adopted for the spatiotemporal analysis of 12-lead ECG. By using this method, the authors find that, in some frequency range, 12-lead ECG has a more complex fractal structure, and the position of the largest singularity strength range delta alpha is not relying on the data length but on the scale factor. By determining the inflexion, the MSMF proves to be more sensitive in displaying the trend that the singularity strength range delta alpha of human ECG decreases with human aging.

Algorithms↗

PubMed2005

Distribution of the novel antifolate pemetrexed to the brain.

Pemetrexed disodium is a novel antifolate that exhibits potent inhibitory effects on multiple enzymes in folate metabolism. Phase II/III clinical trials have shown that pemetrexed is effective against various solid tumors. Like methotrexate, pemetrexed may be useful in treatment of primary and secondary brain tumors. In this study, we examined the central nervous system (CNS) distribution of pemetrexed and the interaction with an organic anion transport inhibitor indomethacin. Male Wistar rats were administered pemetrexed by either single intravenous bolus or constant intravenous infusion. Unbound pemetrexed in blood and brain was measured by simultaneous arterial blood and frontal cortex microdialysis sampling. In the i.v. bolus experiments, indomethacin was administered by i.v. bolus (10 mg/kg) followed by i.v. infusion (0.1 mg/kg/h) in a crossover manner. In the infusion experiments, the same dose of indomethacin was administered after a steady state was reached for pemetrexed. CNS distributional kinetics was analyzed by compartmental and noncompartmental methods. Both bolus and infusion studies showed that pemetrexed has a limited CNS distribution. The mean area under concentration-time curve (AUC)(brain)/AUC(plasma) ratio of unbound pemetrexed was 0.078 +/- 0.038 in the i.v. bolus study. The pemetrexed steady-state brain-to-plasma unbound concentration ratio after i.v. infusion was 0.106 +/- 0.054. The distributional clearance into the brain was approximately 10% of the clearance out of the brain in both the compartmental and noncompartmental analyses. Indomethacin had no effect on either the brain-to-plasma AUC ratio or the steady-state brain-to-plasma concentration ratio. The distribution of pemetrexed into the brain is limited, and an efflux clearance process, such as an efflux transporter, may be involved.

Animals↗

PubMed2005

Mesothelial cell transplantation in the infarct scar induces neovascularization and improves heart function.

OBJECTIVES: Cell transplantation and associated neovascularization in vivo may be beneficial in ischemic disease. We hypothesized that transplanted mesothelial cells (MCs) could improve neovascularization in the post-myocardial infarct scar in rats. METHODS: Myocardial infarction was created by left coronary artery ligation in Lewis rats. After 3 weeks, surviving rats with left ventricular (LV) ejection fraction (EF) <50% were randomized into 2 groups which received, via injection into the infarct scar, either syngeneic rat peritoneal MCs (transplanted group) or vehicle alone (control group). Rats were followed-up echocardiographically for 4 weeks. Before transplantation, cells were transfected in vitro or labeled by a fluorescent dye for subsequent tracking in vivo. Transplanted cells and neovascularization were assessed histologically in the infarct scar by immunostaining or intravenous FITC-dextran injection prior to sacrifice, from 1 to 30 days post-transplantation. RESULTS: Among other pro-angiogenic chemokines, cultured MCs released stromal cell-derived factor (SDF-1alpha) (15.9 +/- 1.8 microg/mg protein) in vitro. At 1 month, some transplanted MCs were visualized (surviving or proliferating) in the LV scar and were incorporated in new vessels. The transplanted rats presented an increased vascular density in the scar, improved LV-EF (44.0 +/- 8.6% vs. 24.0 +/- 4.5%, p < 0.01) with decreased LV end-diastolic diameter (9.6 +/- 0.6 vs. 11.1 +/- 0.6 mm, p < 0.01) and volume (0.47 +/- 0.1 vs. 0.63+/-0.1 ml, p < 0.01) vs. controls. One week post-transplantation, higher levels of SDF-1alpha were extracted from LV peri-infarct tissue (32.3 +/- 5.8 vs. 22.6 +/- 3.1 pg/mg protein in controls, p < 0.01). CONCLUSIONS: Since autologous MCs can be obtained easily and cultured in large quantities, MC transplantation may represent a new angiogenic strategy in the prevention of ischemic remodeling.

Animals↗

PubMed2005

Population fitness and the regulation of Escherichia coli genes by bacterial viruses.

Temperate bacteriophage parasitize their host by integrating into the host genome where they provide additional genetic information that confers higher fitness on the host bacterium by protecting it against invasion by other bacteriophage, by increasing serum resistance, and by coding for toxins and adhesion factors that help the parasitized bacterium invade or evade its host. Here we ask if a temperate phage can also regulate host genes. We find several different host functions that are down-regulated in lysogens. The pckA gene, required for gluconeogenesis in all living systems, is regulated directly by the principal repressor of many different temperate prophage, the cI protein. cI binds to the regulatory region of pckA, thereby shutting down pckA transcription. The pckA regulatory region has target sequences for many other temperate phage repressors, and thus we suggest that down-regulation of the host pckA pathway increases lysogen fitness by lowering the growth rate of lysogens in energy-poor environments, perhaps as an adaptive response to the host predation system or as an aspect of lysogeny that must be offset by down-regulating pckA.

Bacteriophage lambda↗

PubMed2005

Reelin promoter hypermethylation in schizophrenia.

Reelin mRNA and protein levels are reduced by approximately 50% in various cortical structures of postmortem brain from patients diagnosed with schizophrenia or bipolar illness with psychosis. In addition, the mRNA encoding the methylating enzyme, DNA methyltransferase 1, is up-regulated in the same neurons that coexpress reelin and glutamic acid decarboxylase 67. We have analyzed the extent and pattern of methylation within the CpG island of the reelin promoter in genomic DNA isolated from cortices of schizophrenia patients and nonpsychiatric subjects. Ten (The Stanley Foundation Neuropathology Consortium) and five (Harvard Brain Collection) schizophrenia patients and an equal number of nonpsychiatric subjects were selected from each brain collection. Genomic DNA was isolated, amplified (from base pair -527 to base pair +322) after bisulphite treatment, and sequenced. The results show that within the promoter region there were interesting regional variations. There was increased methylation at positions -134 and 139, which is particularly important for regulation, because this portion of the promoter is functionally competent based on transient transfection assays. This promoter region binds a protein present in neuronal precursor nuclear extracts that express very low levels of reelin mRNA; i.e., an oligonucleotide corresponding to this region and that contains methylated cytosines binds more tightly to extracts from nonexpressing cells than the nonmethylated counterpart. Collectively, the data show that this promoter region has positive and negative properties and that the function of this complex cis element relates to its methylation status.

Binding, Competitive↗

PubMed2005

[Influence of pre-transplant serum level of soluble CD30 on the long-term survival rates of kidney transplant recipients and grafts].

OBJECTIVE: To investigate the influence of pre-transplant sCD30 level on the long-term survival rates of kidney transplant recipients and grafts among Chinese. METHODS: A retrospective cohort of 707 patients undergoing cadaver renal transplants between Dec.1998 and Aug 2003, 467 males and 240 females, aged 40 +/- 11, with their blood samples preserved was studied. The plasma levels of sCD30 were determined by ELISA. RESULTS: The 5-year graft survival/functional rates of the high sCD30 group were 77.7% +/- 3.5%/85.0% +/- 3.2%, significantly lower than those of the low and intermediate groups, 84.7% +/- 2.1%/98.9% +/- 1.1% and 88.1% +/- 2.9%/95.1% +/- 1.6% respectively (all P < 0.05). The 5-year recipient survival rate of the intermediate sCD30 group was 92.4% +/- 1.6%, higher than those of the low and high sCD30 groups, 84.7% +/- 3.9% and 87.1% +/- 2.7% respectively with a significant difference between the intermediate and high sCD30 groups (P = 0.032). CONCLUSIONS: Pre-transplant serum level of sCD30 reflects the immune status. Recipients with high sCD30 are prone to rejection while those with low sCD30 are prone to infections.

Adult↗

PubMed2005

Spatial segregation of gamma-secretase and substrates in distinct membrane domains.

Gamma-secretase facilitates the regulated intramembrane proteolysis of select type I membrane proteins that play diverse physiological roles in multiple cell types and tissue. In this study, we used biochemical approaches to examine the distribution of amyloid precursor protein (APP) and several additional gamma-secretase substrates in membrane microdomains. We report that APP C-terminal fragments (CTFs) and gamma-secretase reside in Lubrol WX detergent-insoluble membranes (DIM) of cultured cells and adult mouse brain. APP CTFs that accumulate in cells lacking gamma-secretase activity preferentially associate with DIM. Cholesterol depletion and magnetic immunoisolation studies indicate recruitment of APP CTFs into cholesterol- and sphingolipid-rich lipid rafts, and co-residence of APP CTFs, PS1, and syntaxin 6 in DIM patches derived from the trans-Golgi network. Photoaffinity cross-linking studies provided evidence for the preponderance of active gamma-secretase in lipid rafts of cultured cells and adult brain. Remarkably, unlike the case of APP, CTFs derived from Notch1, Jagged2, deleted in colorectal cancer (DCC), and N-cadherin remain largely detergent-soluble, indicative of their spatial segregation in non-raft domains. In embryonic brain, the majority of PS1 and nicastrin is present in Lubrol WX-soluble membranes, wherein the CTFs derived from APP, Notch1, DCC, and N-cadherin also reside. We suggest that gamma-secretase residence in non-raft membranes facilitates proteolysis of diverse substrates during embryonic development but that the translocation of gamma-secretase to lipid rafts in adults ensures processing of certain substrates, including APP CTFs, while limiting processing of other potential substrates.

Age Factors↗

PubMed2005

Autosomal dominant neurohypophyseal diabetes insipidus with linkage to chromosome 20p13 but without mutations in the AVP-NPII gene.

CONTEXT: Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) has been known as a rare disorder transmitted as an autosomal dominant trait, characterized by polyuria and polydipsia, and caused by deficient neurosecretion of arginine vasopressin precursor (AVP-NPII). We reported an ADNDI family with linkage to chromosome 20p13 but without mutations in the AVP-NPII gene. OBJECTIVE: The objective of this study was to identify the corresponding locus responsible for ADNDI in a family without AVP-NP II gene mutations. SUBJECTS AND METHODS: Two families with ADNDI were diagnosed by water deprivation test. The AVP-NPII gene was amplified by PCR and sequenced. A genomewide scan was performed in one family using 400 microsatellite markers covering 22 autosomes. RESULTS: A 3-bp deletion (1827-1829delAGG) of AVP-NPII gene was identified in the affected individuals in one family. Although no mutations could be detected in the coding, the promoter, and intronic regions of AVP-NPII gene in the other family, a maximum LOD score of 1.202999 (theta = 0.00) was obtained at marker D20S889 by genomewide scan, and a 7-cM interval on chromosome 20p13 was defined by fine mapping with markers D20S199-D20S849. Furthermore, the intragenic region that regulates AVP-NPII and oxytocin expression as an enhancer element and the UBCE7IP5 gene that participates in prohormone degradation were sequenced. No alterations could be detected either. CONCLUSION: The corresponding locus responsible for ADNDI is possibly heterogeneous regarding the slightly different clinical features in these two families.

Adolescent↗

PubMed2005

[Biological impact of the COOH-terminal 40 amino acid deletions of hepatitis B virus X protein in hepatocellular carcinoma cells].

OBJECTIVE: To investigate the biological impact of the wild type hepatitis B virus X protein (HBx) and HBx3'-40, an engineered deletion mutant of HBx lacking the last 40 C-terminal amino acids and a transcriptional transactivator on hepatoma cells. METHODS: Human hepatocellular cells of the lines Huh7 and SMMC-7721 were transfected with HBx3'-40 or HBx constructs. The integration of the plasmid DNA and the expression of HBx3'-40 and HBx were confirmed by Neo gene PCR and Western blotting respectively. The growth curves of different cells were obtained by MTT method. Plate clone formation test to calculate the clone formation rate. Flow cytometry (FCM), and Chloramphenicol acetyl transferase (CAT)-ELISA. Male BALB/c mice were divided into 3 groups to be inoculated subcutaneously with plasmids pcDNA3HBx, pcDNA3HBx3'-40, and blank plasmas pcDNA3 as controls. The mice were killed 15 and 30 days after and the tumors were taken out to undergo measurement and immunohistochemistry. RESULTS: Growth curve showed that after transfection the HBx3'-40 group cells grew faster than HBx and pcDNA3 transfected group cells. FCM analysis showed that HBx3'-40 transfection enhanced the progression of G(1) --> S phase in Huh7 cell cycle and HBx did not show such impact. The clone formation rates of pcDNA3HBx3'-40 group was 12.2% +/- 1.4%, significantly higher than those of the pcDNA3HBx, blank vector, and control groups (6.3% +/- 0.7%, 4.1% +/- 0.9%, and 6.1% +/- 1.1% respectively, all P < 0.05) in the Huh7 cells. The situation was the similar in the SMMC-7721 cells: 83% +/- 6% vs.49% +/- 8%, 27% +/- 3%, and 51% +/- 5% respectively (all P < 0.05). The apoptotic rates of SMMC-7721 cells under no serum condition transfected with HBx and HBx3'-40, especially the former, were 12.57% and 9.15%, significantly higher than that of the pcDNA3HBx group. The CAT expression of the pcDNA3HBx-transfected SMMC-7721 cells was 2.913 and 3.652 times those of the pcDNA3HBx3'-40 group and pcDNA3 group. The tumor weights of the mice inoculated with pcDNA3HBx3'-40, pcDNA3HBx, and blank vector-transfected Huh7 cells were 1.2 g +/- 0.17 g, 0.55 g +/- 0.12 g, and 0.48 g +/- 0.15 g respectively. The tumor weights of the mice inoculated with pcDNA3HBx3'-40, pcDNA3HBx, and blank vector-transfected SMMC-7721 cells showed similar features. CONCLUSION: HBx3'-40 protein significantly promote the proliferation of hepatocellular carcinoma cells and is involved in cell apoptosis and invasion, thus supporting the hypothesis that HBx mutants play a key role in hepatocarcinogenesis by modifying the biological functions of HBx. Besides, C-terminal mutants of HBx makes p53 tumor suppressor gene lose its cancerostatic function.

Animals↗

PubMed2005

Protective effects of 5,4'-dihydroxy-3',5'-dimethoxy-7-O-beta-D -glucopyranosyloxy-flavone on experimental hepatic injury.

AIM: To investigate the pharmacological effects of rice flavone (5,4'-dihydroxy-3',5'-dimethoxy-7-O-beta-D-glucopyranosyloxy-flavone, RF) separated from panicle-differentiating to flowing rice on rat experimental hepatic injury. METHODS: Models of rat acute hepatic injury induced by carbon tetrachloride (CCl(4)) administration, rat hepatic fibrosis induced by thioacetamide, injury of primary cultured rat hepatocytes induced by CCl(4), respectively, were established. After treated with RF, content of serum alanine transaminase (ALT), aspartate aminotransferase (AST) and albumin (Alb), hyaluronic acid (HA), the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and hydroxyproline (Hyp) were measured and liver tissue was observed pathologically by hematoxylin-eosin (HE) staining. Effects of RF on pathological changes, function index, enzyme of scavenging free radicals and blood rheology were evaluated. RESULTS: In model of rat acute hepatic injury induced by CCl(4), RF can significantly decrease the contents of serum ALT, AST, increase the content of Alb, improve the dropsy and fat denaturalization of hepatocytes. In model of rat hepatic fibrosis induced by thioacetamide, RF can inhibit the increase of HA, Hyp and whole blood viscosity, and improve the activities of GSH-Px and SOD, and inauricular microcirculation. CONCLUSION: RF has apparent protective effects on hepatic injury by increasing activity of GSH-Px and SOD, scavenging free radicals produced by CCl(4), reducing blood viscosity, and improving microcirculation and blood supply.

Acute Disease↗

PubMed2005

Antifibrotic effect of interferon gamma in silicosis model of rat.

This study presents the antifibrotic effect of interferon gamma (IFN-gamma) in silicosis of rats. Wistar rats were received saline or 20 mg of quartz by intratracheal instillation. The next day after instillation, silicosis model of rats were daily treated IFN-gamma (1.0 x 10(5) units/rat) or saline by intramuscular route. At 1 month or 2 months after instillation, rats were sacrificed to determine hydroxyproline content and observe the change of fibrosis and expression of interleukin-4 (IL-4) and transforming growth factor-beta1 (TGF-beta1) in the lung of rats. The hydroxyproline content of IFN-gamma treated groups was significantly lower than that of quartz groups (P<0.05). At 1 month after instillation, there were Stage II and II+ of silicotic nodules in quartz group; however, in IFN-gamma treated group only cellular nodules (Stage I) were observed. At 2 months after instillation, there was Stage II+ and III of silicotic nodules in quartz group. In IFN-gamma treated group Stage II was found. The expressions of IL-4 (2.19+/-0.90, 0.61+/-0.22, respectively) and TGF-beta1 (1.37+/-0.31, 1.76+/-0.72, respectively) in IFN-gamma treated groups were significantly lower than those in quartz groups (IL-4: 3.33+/-1.27, 1.99+/-0.80; TGF-beta1: 3.67+/-0.63, 4.90+/-1.11, respectively; P<0.05 or P<0.01). It may be concluded that the decreased expression of IL-4 and TGF-beta1 may be associated with decreased hydroxyproline synthesis, which then results in decreased lung fibrosis.

Animals↗