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Biomedical subjects

Jin Gao

Publications and source records attributed to Jin Gao.

16 recordsLinked to original sources

Kallikrein 4 is a potential mediator of cellular interactions between cancer cells and osteoblasts in metastatic prostate cancer.

BACKGROUND: Prostate cancer (PCa) and bone cell interactions are critical in the metastatic phase. Kallikrein 4 (KLK4/hK4) is expressed in both PCa and mineralized tissues. We determined if KLK4/hK4 expression was associated with, and influenced by, the bone environment of metastatic PCa. METHODS: Immunohistochemistry, in vitro co-culture, cell migration, and attachment assays. RESULTS: hK4 was localized to tumor cells and osteoblasts in bone metastases. KLK4/hK4 increased in LNCaP and PC3 cells co-cultured with SaOs2 cells; SaOs2 KLK4/hK4 was unchanged. Co-culture did not affect cell proliferation but altered alkaline phosphatase activity/mRNA levels in SaOs2 cells. KLK4-transfected PC3 cells had increased migration towards SaOs2 conditioned medium and greater attachment to the bone-matrix proteins, collagens I and IV. CONCLUSIONS: hK4 expression and interaction with both tumor cells and osteoblasts suggests a role for hK4 in PCa bone metastasis. Whether this observation is unique to bone metastasis or reflects a role for hK4 in PCa metastasis generally is yet to be established.

Bone Neoplasms↗

A neuroinductive biomaterial based on dopamine.

Chemical messengers such as neurotransmitters play an important role in cell communication, differentiation, and survival. We have designed and synthesized a bioactive biomaterial that derived its biological activity from dopamine. The resultant biodegradable polymer, PCD, has pendent groups bearing dopamine functionalities. Image analysis demonstrated that nerve growth factor-primed rat pheochromocytoma cells (PC12) and explanted rat dorsal root ganglions attached well and displayed substantial neurite outgrowth on the polymer surface. Furthermore, PCD promoted more vigorous neurite outgrowth in PC12 cells than tissue culture polystyrene, laminin, and poly(d-lysine). The histogram of neurite length of PC12 cells showed distinctive patterns on PCD that were absent on the controls. A subset of PC12 cells displayed high filopodium density on PCD. The addition of dopamine in culture medium had little effect on the differentiation of PC12 cells on tissue culture polystyrene. Tyrosine, the precursor of dopamine, did not exhibit this ability to impart specific bioactivity to an analogous polymer. Thus, the dopamine functional group is likely the origin of the inductive effect. PCD did not cause nerve degeneration or fibrous encapsulation when implanted immediately adjacent to the rat sciatic nerves. This work is a step toward creating a diverse family of bioactive materials using small chemical messengers as monomers.

Animals↗

Astragalus-based Chinese herbs and platinum-based chemotherapy for advanced non-small-cell lung cancer: meta-analysis of randomized trials.

PURPOSE: Systemic treatments for advanced non-small-cell lung cancer have low efficacy and high toxicity. Some Chinese herbal medicines have been reported to increase chemotherapy efficacy and reduce toxicity. In particular, Astragalus has been shown to have immunologic benefits by stimulating macrophage and natural killer cell activity and inhibiting T-helper cell type 2 cytokines. Many published studies have assessed the use of Astragalus and other Chinese herbal medicines in combination with chemotherapy. We sought to evaluate evidence from randomized trials that Astragalus-based Chinese herbal medicine combined with platinum-based chemotherapy (versus platinum-based chemotherapy alone) improves survival, increases tumor response, improves performance status, or reduces chemotherapy toxicity. METHODS: We searched CBM, MEDLINE, TCMLARS, EMBASE, Cochrane Library, and CCRCT databases for studies in any language. We grouped studies using the same herbal combinations for random-effects meta-analysis. RESULTS: Of 1,305 potentially relevant publications, 34 randomized studies representing 2,815 patients met inclusion criteria. Twelve studies (n = 940 patients) reported reduced risk of death at 12 months (risk ratio [RR] = 0.67; 95% CI, 0.52 to 0.87). Thirty studies (n = 2,472) reported improved tumor response data (RR = 1.34; 95% CI, 1.24 to 1.46). In subgroup analyses, Jin Fu Kang in two studies (n = 221 patients) reduced risk of death at 24 months (RR = 0.58; 95% CI, 0.49 to 0.68) and in three studies (n = 411) increased tumor response (RR = 1.76; 95% CI, 1.23 to 2.53). Ai Di injection (four studies; n = 257) stabilized or improved Karnofsky performance status (RR = 1.28; 95% CI, 1.12 to 1.46). CONCLUSION: Astragalus-based Chinese herbal medicine may increase effectiveness of platinum-based chemotherapy when combined with chemotherapy. These results require confirmation with rigorously controlled trials.

Antineoplastic Combined Chemotherapy Protocols↗

Macroporous elastomeric scaffolds with extensive micropores for soft tissue engineering.

Macroporous scaffolds are of great value in tissue engineering. We have developed a method to fabricate macroporous scaffolds from a biocompatible and biodegradable elastomer, poly(glycerol sebacate) (PGS). This method is potentially very useful for soft tissue engineering. Our fabrication method produced macroporous scaffolds with extensive micropores. We fabricated flat scaffolds and tubular scaffolds of uniform thickness. This fabrication method demonstrated good control of variables such as pore size, porosity, and pore interconnectivity. Sodium chloride (salt) crystals, which served as solid porogens, were packed into a mold and fused in a humid chamber. PGS was cured while dispersed throughout the fused salt template. Dissolution of the salt and subsequent lyophilization produced elastomer sponges with approximately 90% porosity, interconnected macropores (75-150 microm), and extensive micropores (5-20 microm). The macropores were generated by the salt particles, while the micropores were likely generated by glycerol vapor formed during PGS curing. Such numerous micropores could facilitate cell-cell interactions and mass transport. Fibroblasts adhered to and proliferated well within the PGS scaffolds and formed three-dimensional tissue-engineered constructs within 8 days.

Animals↗

High level expression of kringle 5 fragment of plasminogen in Pichia pastoris.

Angiogensis can be blocked by inhibitors such as endostatin and angiostatin. The kringle 5 fragment of plasminogen also has a potent inhibitory effect on endothelial cell proliferation and leads to the inhibition of angiogenesis. It has promise in anti-angiogenic therapy due to its small size and potent inhibitory effect. Preparation of kringle 5 has been achieved through the proteolysis of native plasminogen and recombinant DNA technology. Bacterially expressed recombinant kringle 5 is mainly insoluble and expressed at low level. The refolding yield is also low. To produce recombinant human kringle 5 in a large quantity, we have genetically modified a strain of Pichia pastoris. On methanol induction, this strain expressed and secreted biologically active, recombinant kringle 5. The expression level of the engineered strain in culture reached more than 300 mgl(-1). Purification was easily achieved by precipitation, hydrophobic and DEAE ion exchange chromatography. The recovery of recombinant kringle 5 was about 50% after purification. Yeast-expressed kringle 5 has a higher activity in anti-endothelial proliferation than bacterially expressed kringle 5.

Cell Proliferation↗

Chinese herbal medicine and chemotherapy in the treatment of hepatocellular carcinoma: a meta-analysis of randomized controlled trials.

BACKGROUND: Hepatocellular carcinoma (HCC), one of the most common malignancies worldwide, is highly resistant to standard therapy. It is unclear whether chemotherapy, arterial embolization, or arterial chemoembolization improve survival advantage enough to justify their high toxicity. Treatment with Chinese herbal medicine has been explored, combining herbs that stimulate host immune response with those that have cytotoxic activity against HCC cells. The authors sought to evaluate the effectiveness of Chinese herbal medicine combined with chemotherapy. The hypothesis was that Chinese herbal medicine added to chemotherapy for the treatment of HCC would improve survival and tumor response, when compared to treatment with chemotherapy alone. METHODS: The authors searched the databases TCMLARS, PubMed, and EMBASE as well as the bibliographies of studies identified in the systematic search for potentially relevant titles or abstracts of studies in any language. They retained those that (1) treated only HCC patients, (2) were described as randomized or reported that there was no statistical difference between treatment groups, (3) gave patients either Chinese herbal medicine therapy combined with chemotherapy in the treatment group or chemotherapy alone in the control group, and (4) provided data on the number of enrolled subjects and responders and nonresponders for tumor response and survival. The authors used random effects meta-analysis to combine data. RESULTS: Twenty-six studies representing 2079 patients met the inclusion criteria. Chinese herbal medicine combined with chemotherapy, compared to chemotherapy alone, improved survival at 12 months (relative risk [RR], 1.55; 95% confidence interval [CI], 1.39-1.72; P < .000), 24 months (RR, 2.15; 95% CI, 1.75-2.64; P < .000), and 36 months (RR, 2.76; 95% CI, 1.95-3.91; P < .000). Tumor response increased (RR, 1.39; 95% CI, 1.24-1.56; P < .000). CONCLUSIONS: These findings provide promising evidence that combining Chinese herbal medicine with chemotherapy may benefit patients with HCC. Because of the low quality of these studies, these findings should be confirmed through conducting high-quality, rigorously controlled trials.

Carcinoma, Hepatocellular↗

[Swelling characterization of poly (vinyl alcohol) hydrogel for prosthetic intervertebral disc nucleus].

In this study the poly(vinyl alcohol)(PVA) hydrogel elastomer was prepared by freezing-thawing method. The influences of percentage of poly (vinyl alcohol) in hydrogel, pH of solution and swelling temperature upon the swelling characteristic of PVA-hydrogel prosthetic nucleus material were studied. Its micropores were observed using SEM, and the swelling dynamics was further discussed. The experimental results showed that the poly (vinyl alcohol) hydrogel was a kind of network with a lot of micropores, the pore size was related with the PVA content. The maximum swelling ratio decreases when the percentage of PVA in hydrogel, the pH of solution and the swelling temperature were enhanced. The swelling process was described by the equation of swelling dynamics equation. The swelling rate was greatly influenced by the PVA content, the pH of solution and the dimension of hydrogel sample.

Biocompatible Materials↗

A novel two-component system amrB-amkB involved in the regulation of central carbohydrate metabolism in rifamycin SV-producing Amycolatopsis mediterranei U32.

A novel two-component signal transduction system amrB-amkB was cloned from rifamycin SV-producing Amycolatopsis mediterranei U32, and their biochemical functions as a response regulator and a histidine protein kinase, respectively, were proven. The amrB disruption mutant was generated by insertional inactivation with the aparmycin resistance gene. The metabolic response to the absence of amrB gene was determined by a biochemical profiling technique in which the concentration changes of metabolic intermediates were measured by gas chromatography with time-of-flight mass spectrometry (GC/TOF-MS). Although the phenotype analyses of the amrB gene disruption mutant showed no significant change with respect to rifamycin SV production and morphological differentiation, the global metabolomic analyses found the concentration levels of some key intermediates in the TCA cycle and glycolysis pathway were affected by an amrB gene disruption event. The primary results suggested that amrB-amkB genes might be involved in the regulation of central carbohydrate metabolism in A. mediterranei U32.

Actinobacteria↗

[Development of artificial disc nucleus materials (semicrystalline polyvinyl alcohol hydrogel elastomers)].

For the purpose of developing of disc nucleus replacement (semicrystalline PVA hydrogel elastomers) and explorating the possibility of clinical application, in this study,the aqueous PVA solution froze at -20 degrees C for 6-12 h, and then thawed at room temperature for 1-2 h. The same process was repeated 1-3 times. After the specimen was dehydrated in vacuum, a kind of artificial disc nucleus materials (semicrystalline PVA hydrogel elastomers ) was formed. DSC and mechanical tests were conducted to investigate the influence of aqueous PVA solution concentration, of dehydrating in vacuum, and of gamma-ray irradiating upon the degree of crystallity and mechanical properties of PVA hydrogel elastomers.

Biocompatible Materials↗

[Anticancer effects of various fractions extracted from Dioscorea bulbifera on mice bearing HepA].

OBJECTIVE: To investigate the anti-cancer activities and the possible mechanism of Chinese herb Dioscrea bulbifera. METHOD: The herb was extracted sequentially with petroleum ether, ethanol and water. The anticancer screen were carried out in vivo with HepA in mice. RESULT: The inhibitory effects on the formation of ascites volume and HepA cell viability in ascites were found in those extracted fractions except water fraction, the petroleum ether fraction being the strongest. Life span of mice bearing HepA ascites was prolonged after exposed to 100 mg x kg(-1) petroleum ether fraction and shortened after exposed to water fraction significantly. Besides, abnormal microstructure on HepA cells surface was found and it was supposed to be potential effect against viability of HepA which was convinced with the regeneration of HepA cells from ascites in mice exposed to petroleum ether fraction. CONCLUSION: Anticancer active compounds are mainly extracted by petroleum ether from hydrophobic constituents of Dioscrea bulbifera and the anticancer effects were related to direct toxicity on tumor cell.

Alkanes↗

Renal tubule-specific expression and urinary secretion of human growth hormone: a kidney-based transgenic bioreactor growth.

Tissue-specific expression of human genes and secretion of human proteins into the body fluids in transgenic animals provides an important means of manufacturing large-quantity and high-quality pharmaceuticals. The present study demonstrates using transgenic mice that a 3.0 kb promoter of the mouse Tamm-Horsfall protein (THP, or uromodulin) gene directs the specific expression of human growth hormone (hGH) gene in the kidney followed by the secretion of hGH protein into the urine. hGH expression was detected in renal tubules that actively produce the THP, that is, the ascending limb of Henle's loop and distal convoluted tubules. Up to 500 ng/ml of hGH was detected in the urine, and this level remained constant throughout the 10-month observation period. hGH was also detectable in the stomach epithelium and serum in two of the transgenic lines, suggesting position-dependent effects of the transgene and leakage of hGH from the site of synthesis into the bloodstream, respectively. These results indicate that the 3.0 kb mouse THP promoter is primarily kidney-specific and can be used to convert kidney into a bioreactor in transgenic animals to produce recombinant proteins. Given the capacity of urine production independent of age, sex and lactation, the ease of urinary protein purification, and the potentially distinct machinery for post-translational modifications in the kidney epithelial cells, the kidney-based transgenic bioreactor may offer unique opportunities for producing certain complex pharmaceuticals.

Animals↗

[Influence of tumor cells on endothelial cells in vitro].

OBJECTIVE: To observe in vitro changes of endothelial cells after confrontation with tumor cells. METHODS: Dynobeads were used to isolate the endothelial cells from the rat lung. Mouse dendritic cell sarcoma cells (DCS), human gastric carcinoma cells (BGC-823) and mouse lung adenocarcinoma cells (LA795) were added to the endothelial cells when the latter was at the confluence phase. Phase contrast microscope, scanning electro-microscope, immunohistochemistry, transwell and fluorescence dye transfer were used to detect morphological and functional changes of the endothelial cells. RESULTS: Endothelial cells may look like cobble stones or long spindle shaped. Direct contact of tumor cells with endothelial cells induced round vascular-like space formation between confluent endothelial cells. Tumor cells were often found at the newly appeared spaces. Tumor cell conditioned medium could support the growth and promote the locomotion of endothelial cells through transwell. It was observed that luciffer yellow was directly transported from tumor cells to endothelial cells. CONCLUSIONS: Tumor cells can directly induce morphological and functional changes in endothelial cells. Direct intercellular communication between tumor cells and endothelial cells is present.

Animals↗

A new steroidal saponin from Tribulus terrestris Linn.

A new steroidal saponin containing six monosaccharides was obtained from the total plant of Tribulus terrestris and elucidated based on chemical spectroscopic analysis, especially on 2D-NMR technology as 26-0-beta-D-glucopyranosyl-22-methoxy-furostane-3-O-[beta-D-xylopyranosyl(l --> 3)-[beta-D-xylopyranosyl(l --> 2)-beta-D-glucopyranosyl(1 --> 4)]]-[alpha-L-rhamnopyranosy(l --> 2)]-beta-D-galactopyranoside.

Chromatography, Thin Layer↗

Chinese herbal medicine and interferon in the treatment of chronic hepatitis B: a meta-analysis of randomized, controlled trials.

OBJECTIVES: This meta-analysis was conducted to examine the effectiveness of Chinese herbal medicine (either alone or with interferon alfa) in treating chronic hepatitis B. METHODS: We searched the TCMLARS, AMED, CISCOM, EMBASE, MEDLINE, and Cochrane Collaboration databases and then hand-searched the articles' bibliographies. RESULTS: Chinese herbal medicine significantly increased seroreversion of HBsAg and was equivalent to interferon alfa in seroreversion of HBeAg and hepatitis B virus (HBV) DNA; Chinese herbal medicine combined with interferon alfa significantly increased seroreversion of HBsAg, HBeAg, and HBV DNA. The Chinese herbal medicine active component bufotoxin combined with interferon alfa significantly increased HBeAg and HBV DNA seroreversion. The Chinese herbal medicine active component kurorinone was equivalent to interferon alfa in seroreversion of HBeAg and HBV DNA. CONCLUSIONS: Although the quality of existing studies was poor, these data suggest that further trials of Chinese Herbal Medicine and interferon in chronic hepatitis B infection are justified.

Antiviral Agents↗