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Biomedical subjects

Yang Yang

Publications and source records attributed to Yang Yang.

At least 91 records · Page 5Linked to original sources

Zanthoxyli Fructus induces growth arrest and apoptosis of LNCaP human prostate cancer cells in vitro and in vivo in association with blockade of the AKT and AR signal pathways.

Zanthoxyli Fructus belongs to the family of oranges and is used as a seasoning in Asian countries including Japan. This study found that a water extract of Zanthoxyli Fructus possessed anti-tumor activity against a wide variety of cancer cells including those from prostate (LNCaP, DU145, PC-3), breast (MCF-7, T47D, MDA-MB231), lung (NCI-H460, -H520), as well as leukemia (HL-60, NB4, Jurkat) in vitro, as measured by the trypan blue exclusion test. Importantly, Zanthoxyli Fructus slowed the proliferation of LNCaP, DU145, and MDA-MB231 cells present as xenografts in BALB/c nude mice without adverse effects. Further studies explored the molecular mechanism by which Zanthoxyli Fructus inhibited the proliferation of androgen-dependent human prostate cancer LNCaP cells because Zanthoxyli Fructus possessed the strongest anti-tumor activity against these cells. Zanthoxyli Fructus blocked androgen receptor (AR) signaling in conjunction with down-regulation of nuclear levels of AR and induced apoptosis of these cells, as measured by the reporter assay, Western blot analysis, and TUNEL assay, respectively. As expected, Zanthoxyli Fructus also decreased the level of the AR-target molecule, prostate-specific antigen in these cells. Furthermore, Zanthoxyli Fructus inhibited AKT kinase and down-regulated levels of cyclin D1 protein, as measured by the AKT kinase assay with GSK-3alpha/beta as a substrate and Western blot analysis, respectively. Taken together, Zanthoxyli Fructus might be useful as an adjunctive therapeutic agent for the treatment of individuals with a variety of cancer types.

Androgen Receptor Antagonists↗

[Construction and identification of HBD-2 transgenic mice].

Human beta defensin 2 (HBD-2) may play an important role in human defense against infection. Its antimicrobial capacity has been fully documented in in vitro study. In order to evaluae its in vivo effects, we developed an HBD-2 transgenic mouse model. The HBD-2 minigene containing CMV promoter, full length of HBD-2 cDNA and BGH polyA tail was generated by PCR amplification and introduced into the fertilized oocytes of C57 X ICR hybridized mouse by microinjection, and offspring were produced. DNA was isolated from the tails of the mouse pups, and the HBD-2 minigene incorporation was analyzed by PCR using HBD-2 specific primers. The HBD-2 gene expression in the multi-tissues of transgenic mice was determined at mRNA level by RT-PCR and at peptide level by immunohistological staining with the use of HBD-2 monoclonal antibody. The results showed that among 17 F0 transgenic mice, HBD-2 positive signal was determined by PCR in 4 mice, suggesting that HBD-2 minigene has been incorporated into the offspring mice. Meanwhile, a widespread expression of HBD-2 mRNA and peptide was detected in the F1 transgenic mice's multi-tissues such as trachea, lung, intestine, esophagus, testis, spleen, skin, endothelium and brain.

Animals↗

[Sexual hormone levels in semen and germ cell apoptosis].

OBJECTIVE: To explore the relationship between sexual hormones in semen and germ cell apoptosis in male population. METHODS: Sixty-six infertile patients and thirty fertile males were selected randomly. The levels of folicle stimulating hormone ( FSH), prolactin (PRL), luteinizing hormone (LH), and testosterone (T) in semen were measured by ELISA. Terminal deoxynucleotidyl transferase mediated UTP nick end labeling (TUNEL) was used for the detection of germ cell apoptosis. RESULTS: The levels of FSH, LH, PRL, T in thirty fertile men were (1.63 +/- 0.15) U/L, (2.18 +/- 0.21) U/L, (6.34 +/- 0.30) nmol/L, (1.85 +/- 0.11) nmol/L, respectively, and germ cell apoptosis rate was (4.61 +/- 1.23)%. FSH, LH, PRL, T levels in infertile group were (1.25 +/- 0.18) U/L, (1.76 +/- 0.32) U/L, (5.86 +/- 0.13) nmol/l, (1.45 +/- 0.13) nmol/, respectively, and germ cell apoptosis rate was (18.36 +/- 2.04)%. There were significant differences in all parameters between infertile group and fertile group. The levels of FSH, LH, PRL, T were negatively correlated with germ cell apoptosis rates( r = -0.88, -0.93, -0.90, -0.98). The volume of apoptotic germ cell decreased, and chromatin was compacted to form cell-membrane blebs and apoptotic bodies. CONCLUSION: Low concentration of sexual hormones may increase the apoptosis of germ cells, which can induce male infertility.

Adult↗

[Influence of temperature, pH value and organic substance on activity of ANAMMOX sludge].

Influence of temperature, pH and organics on ANAMMOX activity was investigated through measuring the anaerobic ammonia oxidation rate of sludge. Results show that temperature and pH could influence ANAMMOX activity dramatically. The optimal temperature was between 30-35 degrees C , and the relationship between the anaerobic ammonia oxidation rate and temperature can be described by revised Arrhenius formula during 20-30 degreee C. The optimal pH was between 7.5 - 8.3, and the relationship between the anaerobic ammonia oxidation rate and pH can be described by two substrates and two inhibitors model during pH 7.0 - 9.0. There was substrata competition between the heterotrophic denitrification bacteria and ANAMMOX bacteria when organics in the

Anaerobiosis↗

[Effects of the HLA antibodies on allograft acute rejection after cadaveric liver transplantation].

OBJECTIVE: To evaluate the effect of perioperative HLA antibody changes on acute allograft rejection in cadaveric liver transplantation. METHODS: Totally 134 patients received modified piggyback liver transplantation and enzyme-linked immunosorbent assay was performed for HLA antibody detection before and the 1, 7, 14 and 30 days after operation. B ultrasound-guided liver biopsy was employed for diagnosis of acute allograft rejection, and the perioperative changes of HLA antibodies were evaluated for their effect on allograft acute rejection. RESULTS: Of the 44 recipients with preoperative positivity for HLA antibodies, acute rejection occurred in 56.8% of the patients, as compared with 25.9% in those negative for HLA antibody (P=0.001). The patients who became positive for HLA antibody postoperatively had a rate of acute rejection of 60%, which was significantly higher than that in those persistently negative for HLA antibody (18.6%, P=0.003). CONCLUSION: HLA antibody positivity before transplantation may contribute to acute rejection episode in liver transplantation, and persistent posttransplant HLA antibody positivity is closely associated with the occurrence of acute rejection.

Adult↗

PC-SPES down-regulates COX-2 via inhibition of NF-kappaB and C/EBPbeta in non-small cell lung cancer cells.

Aberrant expression of COX-2 occurs in many types of malignancies including colon and lung cancers, and is implicated in development and progression of cancer. The molecular mechanisms associated with aberrant expression of COX-2 in lung cancer cells remain to be fully elucidated. In this study, we found that non-small cell lung cancer (NSCLC) NCI-H520 and NCI-H460 cells constitutively expressed COX-2 and produced prostaglandin E2 (PGE2) as measured by Western blotting and enzyme-linked immunosorbent assay (ELISA), respectively. Reporter assays showed that transcriptional regulation of COX-2 was blunted when either the NF-IL6 (C/EBPbeta) or nuclear factor-kappaB (NF-kappaB) binding site in the COX-2 promoter was mutated, suggesting that C/EBPbeta and NF-kappaB transcription factors have an important role in aberrant expression of COX-2 in these lung cancer cells. In addition, the eight herbal mixture PC-SPES (Lot. 5431219) caused growth arrest and apoptosis of NCI-H520 and NCI-H460 cells in association with blockade of NF-kappaB and down-regulation of C/EBPbeta, resulting in down-regulation of COX-2 and PGE2 in these cells. On the other hand, PC-SPES up-regulated the level of C/EBPbeta in these cells. Taken together, C/EBPbeta and NF-kappaB may be promising molecular targets for COX-2 inhibition in lung cancer cells. PC-SPES might be useful in the adjuvant setting for the treatment of individuals with resected NSCLC as well as other types of cancer in which COX-2 is activated.

Antineoplastic Agents, Phytogenic↗

[Effect of cortisol on ischemic preconditioning in rabbit hearts].

OBJECTIVE: To determine the effects of reacting cortisol on ischemic preconditioning (IPC). METHODS: Thirty rabbits were randomized into ischemic preconditioning (IPC) group, etomidate (Etom) group, ischemic/reperfusion (IR) group, methylprednisolone (MP) group and a control group. The ratios of infarction size versus risk area (Infarct/Risk) were calculated. The elevations of serum CK activity and cTnI concentrations as well as serum cortisol concentrations were measured. RESULTS: The ratios of Infarct/Risk were 5.9%+/-2.8% for IPC, 11.3%+/-3.6% for Etom, 26.8%+/-4.5% for IR and 18.2%+/-3.7% for MP. The elevations of serum CK activity (U/L) were 255+/-89 for IPC, 314+/-160 for Etom, 855+/-371 for IR and 768+/-404 for MP, the elevations of serum cTnI concentrations (microg/L) were 3.6+/-0.6 for IPC, 5.9+/-2.0 for Etom, 8.1+/-3.6 for IR and 6.1+/-2.3 for MP. Those indicators among groups are all significantly different (P<0.01). Cortisol reacting was markedly diminished in Etom group. CONCLUSION: A blunted cortisol reaction can markedly undermine the benefit of ischemic preconditioning, methylprednisolone show a certain myocardial protection. Cortisol may play an important role in the IPC process.

Animals↗

[Community structure of nitrification bacteria in aerobic short-cut nitrification granule].

By using a lab-scale aerated upflow sludge bed reactor, the inoculated anaerobic granule was cultivated to aerobic nitrification granule, and then converted to short-cut nitrification granule with the short-cut nitrification efficiencies above 90%. Appling real-time quantity PCR, and florescent in situ hybridization techniques, the ecological community structure of nitrification bacteria in aerobic granules were studied. The results show that there existed a layered structure in the aerobic granule, the ammonia oxidizing bacteria (AOB) was mainly located in the surface area of the granule, and the nitrite oxidizing bacteria (NOB) was mainly located in the inner area of the granule, was just adjacent to the AOB. There was no active bacteria in the inner core area. The amount of AOB in the granules increased, as the ammonia loading rate of the reactor was increased gradually. The percentage of AOB in the total amount of Eubacteria in the granule was 0.45%, 5.20%, 15.37%, 48.55% respectively, as the ammonia loading rate of the reactor were 0, 0.4, 1.0 and 2.2 kg/(m3 x d) respectively, and the nitrosofication efficiency were 0%, 35%, 50%, 99% relatively.

Aerobiosis↗

[Standardization of rat stable orthotopic liver transplantation model and comparison of the effect of two liver graft perfusion methods].

OBJECTIVE: To standardize the establishment of a stable rat model of orthotopic liver transplantation and surgical technique of two-cuff technique for improving the operation success rate, and compare the effect of graft perfusion via the portal vein and the abdominal aorta on the graft function. METHODS: Totally 100 cases of orthotopic liver transplantation was performed in rats under microscope according to modified Kamada's two cuff technique. The rats were divided into 2 groups with the donor liver perfused through the portal vein with 10 ml cold lactated Ringer's solution, and via the abdominal aorta with 20 ml cold lactated Ringer's solution, respectively. The postoperative function recovery and pathological changes of the liver grafts were evaluated by serum ALT detection and histopathological examination. The operation success rate, 3-month survival rate of the rats and the complications were observed. RESULTS: No significant differences was noted in the liver function, operation success rate and 3-month survival rate between the 2 groups, and histopathological examination also showed similar findings. The success rates of the two groups were 98% and 96%, with 3-month survival rate of 93.5% (29/31) and 93.3% (28/30) (P>0.05), respectively. CONCLUSION: The liver transplantation models with portal vein or abdominal aorta graft perfusion both serve well their respective purposes. Good microsurgical skills, standardized performance and shortened anhepatic period are the keys to improved stability and survival rate and reduced operative complications.

Animals↗

[The expression of extracellular matrix in epithelial ingrowth after LASIK].

PURPOSE: To observe the expression of extracellular matrix in cornea and its relationship with corneal opacity after epithelial ingrowth in LASIK. METHODS: Corneal flap was made on rabbit eyes, and epithelial cells mechanically scraped from surroundings the flap were implanted underneath. The corneas were harvested 1, 3, 7 and 30 days following surgery, histological and immunohistochemical examination was performed. RESULTS: On slit-lamp examination, corneal opacity was observed in the area where epithelial cells were implanted. Histological study revealed clusters of epithelial cells at the flap and stroma bed interface. One week and one month post-operation intense immunoreactivity for collagen type IV was detected at the perimeters of the intrastromal epithelial island, but not in the ordinary interface area, strong staining for collage type III was also observed around the epithelial islands. CONCLUSION: The marked deposition of collagen type IV surrounding the ingrowth epithelial cells indicated that it might be the essential component of interface haze in epithelial ingrowth after LASIK.

Animals↗

[The role of caspase-3 in rapamycin-induced apoptosis of hepatocellular carcinoma BEL-7402 cells].

BACKGROUND & OBJECTIVE: Rapamycin, isolated from Streptomyces hygroscopicus, is recently reported to have immunosuppressive and antitumor effects on a large variety of cancers. This study was to investigate the role of Caspase-3 in rapamycin-induced apoptosis of hepatocellular carcinoma BEL-7402 cells. METHODS: BEL-7402 cells were treated with different concentrations (5, 10, 20, 30, 40, 50 nmol/L) of rapamycin. Cell viability was detected by MTT assay; cell apoptosis was observed by flow cytometry (FCM) and Hoechst 33258 staining. The activity of Caspase-3 was determined by Caspase colorimetric assay kit and Western blot. RESULTS: Rapamycin inhibited the growth of BEL-7402 cells and induced apoptosis significantly in time- and dose-dependent manners. Marked morphologic changes of cell apoptosis, such as chromatin condensation and nuclear fragmentation, were observed clearly at 48 h after exposion to rapamycin; Caspase-3 was activated by the loss of Caspase-3 proenzyme (32-ku) and its 20-ku subunit appeared at 24 h after incubation. Caspase-3 inhibitor z-DEVD-FMK could block the apoptosis induced by rapamycin. CONCLUSIONS: Rapamycin can inhibit growth and induce apoptosis of BEL-7402 cells. The activation of Caspase-3 may play an important role in cell apoptosis.

Antibiotics, Antineoplastic↗

S-adenosyl-L-homocysteine hydrolase inactivation curtails ovalbumin-induced immune responses.

The reversible S-adenosyl-L-homocysteine (AdoHcy) hydrolase inhibitor methyl 4-(adenin-9-yl)-2-hydroxybutanoate (DZ2002) suppresses macrophage activation and function. The effects of DZ2002 on T cell function, however, are still unclear. Here, we examined whether DZ2002 alters type 1 helper T cell (Th1) and/or type 2 helper T cell (Th2) immune responses, and whether these effects are associated with both the inhibition of AdoHcy hydrolase and intracellular elevation of endogenous AdoHcy. Male C57BL/6 mice immunized with ovalbumin (OVA) were treated with DZ2002 (1, 5, and 25 mg/kg/day) after which lymphocyte proliferation, cytokine production, and IgG responses to OVA were monitored. Administration of DZ2002 dose dependently suppressed OVA-specific lymphocyte proliferation and anti-OVA IgG production compared with controls. Interleukin (IL)-2 and interferon (IFN)-gamma as well as anti-OVA IgG2a and IgG3, indicators of Th1 immune responses, were markedly decreased in mice treated with DZ2002, whereas IL-4 and anti-OVA IgG1, indicators of Th2 immune responses, were only mildly suppressed. AdoHcy hydrolase activity in spleens of DZ2002-treated mice was substantially blocked, and not surprisingly, AdoHcy levels were significantly elevated compared with controls. Finally, similar immunosuppressive effects were also observed in mice treated with AdoHcy. These data strongly indicate that DZ2002 suppresses antigen-induced specific immune responses, particularly Th1 responses, through inhibition of AdoHcy hydrolase and elevation of endogenous AdoHcy.

Adenine↗

Enzymatic remodeling of heparan sulfate proteoglycans within the tumor microenvironment: growth regulation and the prospect of new cancer therapies.

Heparan sulfate proteoglycans (HSPGs), via their interactions with numerous effector molecules such as FGF-2, IL-8, and VEGF, regulate the biological activity of cells by acting as co-receptors that promote signaling. The extent and nature of their role as co-receptors is often misregulated in cancer as manifested by alterations in HSPG structure and expression level. This misregulation of HSPGs can aid in promoting the malignant phenotype. In addition to expression-related changes in HSPGs, recent discoveries indicate that HSPGs localized within the tumor microenvironment can be attacked by enzymes that alter proteoglycan structure resulting in dramatic effects on tumor growth and metastasis. This review focuses on remodeling of HSPGs by three distinct mechanisms that occur in vivo; (i) shedding of proteoglycan extracellular domains from cell surfaces, (ii) fragmentation of heparan sulfate chains by heparanase, and (iii) removal of sulfates from the 6-O position of heparan sulfate chains by extracellular sulfatases. Assessing or monitoring the remodeling of HSPGs has important implications for tumor diagnosis and patient prognosis while therapeutic manipulation of the remodeling process represents an exciting new possibility for treating cancer.

Animals↗

[Diagnosis and treatment of cytomegalovirus pneumonia after liver transplantation].

OBJECTIVES: To investigate the diagnosis and treatment of cytomegalovirus (CMV) pneumonia after liver transplantation. METHODS: Five cases of CMV pneumonia after liver transplantation were analyzed retrospectively. CMV pneumonia was diagnosed according to its clinical manifestation, chest X-ray, and etiologic test. All 5 patients received comprehensive therapy based on anti-virus treatment and immunologic adjustment. RESULTS: The clinical manifestation of CMV pneumonia after liver transplantation was nonspecific. Its main symptoms included fever, cough, dyspnea, tachycardia, fatigue, hypoxemia and neutropenia. The chest X-ray showed interstitial pneumonia. Sera CMV antigens or antibodies could be detected in the patients. Four patients were cured and 1 patient died. CONCLUSIONS: The clinical manifestation of CMV pneumonia was nonspecific. CMV pneumonia could be diagnosed according to its manifestations, chest X-ray and etiologic test. The comprehensive therapy based on anti-virus treatment and immunologic adjustment was effective for the disease.

Adult↗

Diabetes resistance/susceptibility in T cells of nonobese diabetic mice conferred by MHC and MHC-linked genes.

Polymorphism of MHC and MHC-linked genes is tightly associated with susceptibility to type 1 diabetes (T1D) in human and animal models. Despite the extensive studies, however, the role of MHC and MHC-linked genes expressed by T cells on T1D susceptibility remains unclear. Because T cells develop from TCR(-) thymic precursor (pre-T) cells that undergo MHC restriction mediated by thymic stroma cells, we reconstituted the T cell compartment of NOD.scid-RIP-B7.1 mice using pre-T cells isolated from NOD, NOR, AKR, and C57BL/6 (B6) mice. T1D developed rapidly in the mice reconstituted with pre-T cells derived from NOD or NOR donors. In contrast, most of the NOD.scid-RIP-B7.1 mice reconstituted with pre-T cells from AKR or B6 donors were free of T1D. Further analysis revealed that genes within MHC locus of AKR or B6 origin reduced incidence of T1D in the reconstituted NOD.scid-RIP-B7.1 mice. The expression of MHC class I genes of k, but not b haplotype, in T cells conferred T1D resistance. Replacement of an interval near the distal end of the D region in T cells of B6 origin with an identical allele of 129.S6 origin resulted in T1D development in the reconstituted mice. These results provide evidence that the expression of MHC class I and MHC-linked genes in T cells of NOD mice indeed contributes to T1D susceptibility, while expression of specific resistance alleles of MHC or MHC-linked genes in T cells alone would effectively reduce or even prevent T1D.

Animals↗

Downregulation of vascular endothelial growth factor and integrinbeta3 by endostatin in a mouse model of retinal neovascularization.

Retinal neovascularization is among the leading causes of vision impairment throughout the world. Intraocular expression of vascular endothelial growth factor (VEGF), an angiogenic protein, and integrins, a group of cell adhesion molecules, is closely correlated with neovascularization in such neovascular diseases. The purpose of this study is to determine the effect of endostatin, a potent anti-angiogenic factor, on gene expression of vascular endothelial growth factor (VEGF) and integrinbeta3 in a mouse model of oxygen-induced retinopathy. C57BL/6 mice were given intravitreous injections of 1.0 microg endostatin at P12. At P17, retinal VEGF and integrinbeta3 mRNA levels were measured by real-time quantitative PCR in the hyperoxia mice and in the endostatin-treated mice. Analysis of 12 separate experiments revealed a 3.5-fold decrease in VEGF levels between hyperoxia mice and endostatin-treated mice (p<0.01) and a 2.5-fold decrease in integrinbeta3 levels between hyperoxia mice and endostatin-treated mice (p<0.01). These data suggest that intraocular expression of VEGF and integrinbeta3 mRNA is down-regulated by endostatin, which may provide a new therapeutic approach for ocular neovascularization.

Angiogenesis Inhibitors↗

HSulf-1 and HSulf-2 are potent inhibitors of myeloma tumor growth in vivo.

To participate as co-receptor in growth factor signaling, heparan sulfate must have specific structural features. Recent studies show that when the levels of 6-O-sulfation of heparan sulfate are diminished by the activity of extracellular heparan sulfate 6-O-endosulfatases (Sulfs), fibroblast growth factor 2-, heparin binding epidermal growth factor-, and hepatocyte growth factor-mediated signaling are attenuated. This represents a novel mechanism for regulating cell growth, particularly within the tumor microenvironment where the Sulfs are known to be misregulated. To directly test the role of Sulfs in tumor growth control in vivo, a human myeloma cell line was transfected with cDNAs encoding either of the two known human endosulfatases, HSulf-1 or HSulf-2. When implanted into severe combined immunodeficient (SCID) mice, the growth of these tumors was dramatically reduced on the order of 5- to 10-fold as compared with controls. In addition to an inhibition of tumor growth, these studies revealed the following. (i) HSulf-1 and HSulf-2 have similar functions in vivo. (ii) The extracellular activity of Sulfs is restricted to the local tumor cell surface. (iii) The Sulfs promote a marked increase in extracellular matrix deposition within tumors that may, along with attenuated growth factor signaling, contribute to the reduction in tumor growth. These findings demonstrate that dynamic regulation of heparan sulfate structure by Sulfs present within the tumor microenvironment can have a dramatic impact on the growth and progression of malignant cells in vivo.

Animals↗

In vivo visualization of cardiac allograft rejection and trafficking passenger leukocytes using bioluminescence imaging.

BACKGROUND: We investigated the feasibility of bioluminescence imaging (BLI) for the in vivo assessment of cardiac allograft viability and visualization of passenger leukocytes during the course of acute rejection. METHODS AND RESULTS: Hearts of FVB (H-2q) luciferase-green fluorescent protein transgenic mice (beta-actin promoter) or FVB luciferase transgenic mice (CD5 promoter) were heterotopically transplanted into either BALB/c (H-2d) or FVB recipients. Light intensity emitting from the recipient animals was measured daily by in vivo BLI until 12 days after transplantation. Graft beating score (0 to 4) was assessed by daily abdominal palpation until 12 days after transplantation. Inflammatory cell infiltration (CD45 stain) and structural changes of green fluorescent protein-positive cardiomyocytes were followed by immunohistochemistry. All cardiac allografts were acutely rejected by 12 days after transplantation. The intensity of light emitting from cardiac allografts declined 4 days after transplantation and correlated with graft beating scores (R2=0.91, P=0.02). Immunohistochemistry confirmed these results by showing an increase of CD45+ inflammatory cell infiltration and destruction of green fluorescent protein-positive cardiomyocytes in the cardiac allografts during acute rejection. In vivo BLI visualized migration and proliferation of CD5+ passenger leukocytes in both syngeneic and allogeneic recipients. In the allograft recipients, light signal from CD5+ passenger leukocytes peaked at 6 hours and diminished by 12 hours, whereas in the syngeneic recipients, the signal remained high until 10 days after transplantation. CONCLUSIONS: BLI is a useful modality for the quantitative assessment of in vivo cardiac graft viability and tracking of passenger leukocytes in vivo during the course of acute rejection.

Animals↗