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Biomedical subjects

Bin Xu

Publications and source records attributed to Bin Xu.

At least 55 records · Page 3Linked to original sources

[In vitro vasculogenesis and angiogenesis of mouse embryonic stem cells].

OBJECTIVE: To explore an optional condition to induce mouse embryonic stem (ES) cells to differentiate into endothelial cells and to establish in vitro models of vasculogenesis and angiogenesis. METHODS: Mouse ES cells were cultured in differentiation medium containing a cocktail of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-6 (IL-6) and erythropoietin (EPO) in 1% methylcellulose to induce formation of embryoid bodies (EBs). At day 11, EBs were harvested and suspended in rat-tail collagen type I with the same cocktail of cytokines cultured for three additional days. The differentiation of ES cells into endothelial cells, processes of vasculogenesis and angiogenesis were examined using immunostaining of EBs slices and whole-mount immunocytochemistry of EBs with monoclonal antibodies (mAbs) against platelet endothelial cell adhesion molecule-1 (PECAM-1) and alpha-smooth muscle actin (SMA). RESULTS: Under appropriate culture conditions; ES cells spontaneously differentiated and formed EBs containing vascular structures and tubular channels, which were positive for PECAM-1 co-differentiated with smooth muscle. When not treated with angiogenic growth factors, PECAM-1-positive cells could not organize into vascular structures of 11-day-old EBs. In the presence of angiogenic factors 11-day old EBs embedded into type I collagen, and rapidly developed an endothelial networks. Whole-mount immunocytochemistry of collagen gel with anti-PECAM-1 antibody showed the formation of primary vascular structures sprouting from EBs. Quantitative analysis revealed that 100 microg/ml thalidomide significantly reduced the number and length of EBs endothelial sprouting. CONCLUSIONS: Mouse ES cells can differentiate into endothelial cells combined with smooth muscle differentiation during EBs formation and further develop endothelial outgrowths after EBs embedded into collagen, which respectively recapitulate vasculogenesis, angiogenesis, and arteriogenesis processes in vivo. The models provide a useful tool to investigate vasculogenesis, angiogenesis, and arteriogenesis mechanisms and evaluate the effects of angiogenic and angiostatic agents.

Animals↗

Chemical and biological flocculation process to treat municipal sewage and analysis of biological function.

The pilot-scale experimental apparatus and the procedure of the chemical and biological flocculation process to verify the feasibility in treating Shanghai municipal sewage were introduced in this paper. In addition, the biological function of the process was discussed. The results of optimal running showed that in the reaction tank, the concentration of mixed liquor suspended solid(MLSS) was 2 g/L, hydraulic retention time(HRT) was 35 min, dosage of liquid polyaluminium chloride(PAC) was 60 mg/L, and the concentration of polyacrylamide(PAM) was 0.5 mg/L. The effluent average concentrations of COD(Cr), TP, SS and BOD5 were 50 mg/L, 0.62 mg/L, 18 mg/L, and 17 mg/L, respectively. These were better than the designed demand. In addition, the existence of biological degradation in this system was proven by several methods. The removal efficiencies of the chemical and biological flocculation process were 20% higher than that of the chemical flocculation process above at the same coagulant dosage. The treatment process under different situations was evaluated on a pilot-scale experiment, and the results provided magnificent parameters and optimal condition for future operation of the plant.

Acrylic Resins↗

[Value of enteroscopy in localization diagnosis of small intestinal hemorrhage].

OBJECTIVES: To study the value of enteroscopy in determining bleeding lesion of small intestine. METHODS: Clinical data of ten cases with small intestinal bleeding diagnosed by enteroscopy were analyzed retrospectively from June 2003 to June 2004. RESULTS: Bleeding sites disclosed by enteroscopy were consistent with those confirmed by operation in 10 patients,but qualitative diagnosis was not consistent in 2 patients. CONCLUSIONS: Enteroscopy is a safe,reliable and valuable modality for diagnosing bleeding lesion of small intestine.

Adolescent↗

[High expression of mirobial transglutaminase gene from Streptoverticillium mobaraense in Escherichia coli].

The microbial transglutamunase (MTG) gene was amplified from the genomic DNA of Streptoverticillium mobaraensea by using PCR and inserted into pET vector to construct the expression plasmid called pET-MTG. The pET-MTG was transfected into E. coli (Rosetta DE3) and the MTG protein was found to be highly expressed as inclusion bodies. The inclusion bodies were isolated and subjected to denaturation and re-naturation, followed by strong cation ion-exchange chromatography to purify the expressed MTG. The specific activity of purified MTG was close to that of native MTG. Taken together, this study might provide a base for the industrial production of microbial transglutaminase.

Bacterial Proteins↗

[Clinical study on electroacupuncture combined with manual acupuncture for treatment of simple obesity].

OBJECTIVE: To compare therapeutic effects of electroacupuncture combined with manual acupuncture and simple electroacupuncture on simple obesity. METHODS: One hundred and twenty cases were randomly divided into an electroacupuncture plus manual acupuncture group (observation group, n = 63) and a simple electroacupuncture group (electroacupuncture group, n = 57). Their clinical therapeutic effects and the time starting the therapeutic effect were compared. RESULTS: In the observation group 57 cases (90.5%) were cured and the total effective rate was 100.0%, and in the electroacupuncture group 42 cases (73.7%) were cured and the total effective rate was 96.5%, with significant difference in the cured rate between the two groups (P < 0.05); and the time starting the therapeutic effect in the observation group was superior to the electroacupuncture group. CONCLUSION: Electroacupuncture combined with manual acupuncture is superior to the simple electroacupuncture in the cured rate and the time starting the effect in treatment of simple obesity.

Acupuncture Therapy↗

[Effect of acupuncture on plasma peptide YY in the patient of simple obesity].

OBJECTIVE: To observe changes of plasma peptide YY (PYY) in acupuncture for slimming. METHODS: Thirty-four cases of simple obesity were treated with acupuncture for 3 courses. Body mass index (BMI), and fat percent (F%), and insulin, PYY, blood fat, and blood sugar levels before and after treatment were determined, with 20 normal persons used as controls. RESULTS: The clinical total effective rate was 88.23%. Acupuncture could increase the decreased insulin sensitive index and PYY level (both P < 0.01), with no correlativity between them (P > 0.05). CONCLUSION: Regulation of PYY is possibly one of the mechanisms of acupuncture in slimming, but the relation of PPY with insulin resistance remains to be studied.

Body Mass Index↗

Enhancing the activity of insulin at the receptor interface: crystal structure and photo-cross-linking of A8 analogues.

The receptor-binding surface of insulin is broadly conserved, reflecting its evolutionary optimization. Neighboring positions nevertheless offer an opportunity to enhance activity, through either transmitted structural changes or introduction of novel contacts. Nonconserved residue A8 is of particular interest as Thr(A8) --> His substitution (a species variant in birds and fish) augments the potency of human insulin. Diverse A8 substitutions are well tolerated, suggesting that the hormone-receptor interface is not tightly packed at this site. To resolve whether enhanced activity is directly or indirectly mediated by the variant A8 side chain, we have determined the crystal structure of His(A8)-insulin and investigated the photo-cross-linking properties of an A8 analogue containing p-azidophenylalanine. The structure, characterized as a T(3)R(3)(f) zinc hexamer at 1.8 A resolution, is essentially identical to that of native insulin. The photoactivatable analogue exhibits efficient cross-linking to the insulin receptor. The site of cross-linking lies within a 14 kDa C-terminal domain of the alpha-subunit. This contact, to our knowledge the first to be demonstrated from the A chain, is inconsistent with a recent model of the hormone-receptor complex derived from electron microscopy. Optimizing the binding interaction of a nonconserved side chain on the surface of insulin may thus enhance its activity.

Amino Acid Sequence↗

Antitumor effects of two bisdioxopiperazines against two experimental lung cancer models in vivo.

BACKGROUND: Probimane (Pro), an anti-cancer agent originating in China, was derived from razoxane (ICRF-159, Raz), a drug created in Britain, specifically targeting at cancer metastasis and as a cardioprotectant of anthrocyclines. Pro and Raz are bisdioxopiperazine compounds. In this work, we evaluated the anti-tumor and anti-metastatic effects of Pro and Raz in vivo against two lung tumor models, one of murine origin (Lewis lung carcinoma, LLC) and one of human origin (LAX-83). RESULTS: After determining the lethal dosage of Pro and Raz, we assessed and compared the inhibitory effects of Pro and Raz against primary tumor growth and metastatic occurrences of LLC at the dosage of LD5. Pro and Raz were active against primary tumor growth and significantly inhibited pulmonary metastasis of LLC at same dose-ranges (inhibitory rates > 90 %). Both Raz and Pro were effective in 1, 5, and 9 day administration schedules. Three different schedules of Raz and Pro were effective against the primary tumor growth of LLC (35-50 %). The synergistic anticancer effect of Raz with bleomycin (Ble) (from 41.3 % to 73.3 %) was more obvious than those with daunorubicin (Dau) (from 33.1 % to 56.3 %) in the LLC tumor model. Pro was also seen to have synergistic anti-cancer effects with Ble in the LLC model. Both Raz and Pro inhibited the growth of LAX 83 in a statistically significant manner. CONCLUSIONS: These data suggest that both Raz and Pro may have anti-tumor potentiality and Raz and Pro have combinative effects with Ble or Dau. The potential targets of bisdioxopiperazines may include lung cancers, especially on tumor metastasis. The anti-cancer effects of Raz and Pro can be increased with the help of other anticancer drugs.

Animals↗

Heparanase mRNA expression and point mutation in hepatocellular carcinoma.

AIM: To explore the expression of heparanase mRNA and point mutation in hepatocellular carcinoma (HCC). METHODS: Reverse transcription polymerase chain reaction was used to measure the expression of heparanase mRNA in the primary tumor tissues and surrounding liver tissues of 33 HCC patients. T-A cloning and sequencing were used to detect whether there was any mutation in the amplified PCR products. RESULTS: The expression of heparanase mRNA was positive in 16 primary tumor tissues of HCC, and the positive rate was 48.5%, which was significantly higher than that in the surrounding liver parenchyma (P<0.01). The positive rate for heparanase gene in high-tendency to metastatic recurrence group (71.4%, 10/14) was obviously higher than that in low-tendency to metastatic recurrence group (31.6%, 6/19) (P = 0.023). The positive rate for heparanase gene in patients with metastatic recurrence during postoperative follow-up (78.6%, 11/14) was also significantly higher than that in those without metastatic recurrence (21.4%, 3/14) (P = 0.003). Sequence analysis of the HPA PCR products was made in 7 patients, and 2-point mutations were found in 4 patients, one of which was sense mutation, neither base insertion nor deletion was detected. The mutation rate was 57.1% (4/7). CONCLUSION: The expression rate of heparanase mRNA increases in HCC, and HPA mRNA may be one of the reliable markers for the metastatic activity gained by the liver tumor cells and could be used clinically in predicting metastatic recurrence of HCC. Point mutation may be one of the causes for enhanced heparanase mRNA expression.

Base Sequence↗

How insulin binds: the B-chain alpha-helix contacts the L1 beta-helix of the insulin receptor.

Binding of insulin to the insulin receptor plays a central role in the hormonal control of metabolism. Here, we investigate possible contact sites between the receptor and the conserved non-polar surface of the B-chain. Evidence is presented that two contiguous sites in an alpha-helix, Val(B12) and Tyr(B16), contact the receptor. Chemical synthesis is exploited to obtain non-standard substitutions in an engineered monomer (DKP-insulin). Substitution of Tyr(B16) by an isosteric photo-activatable derivative (para-azido-phenylalanine) enables efficient cross-linking to the receptor. Such cross-linking is specific and maps to the L1 beta-helix of the alpha-subunit. Because substitution of Val(B12) by larger side-chains markedly impairs receptor binding, cross-linking studies at B12 were not undertaken. Structure-function relationships are instead probed by side-chains of similar or smaller volume: respective substitution of Val(B12) by alanine, threonine, and alpha-aminobutyric acid leads to activities of 1(+/-0.1)%, 13(+/-6)%, and 14(+/-5)% (relative to DKP-insulin) without disproportionate changes in negative cooperativity. NMR structures are essentially identical with native insulin. The absence of transmitted structural changes suggests that the low activities of B12 analogues reflect local perturbation of a "high-affinity" hormone-receptor contact. By contrast, because position B16 tolerates alanine substitution (relative activity 34(+/-10)%), the contribution of this neighboring interaction is smaller. Together, our results support a model in which the B-chain alpha-helix, functioning as an essential recognition element, docks against the L1 beta-helix of the insulin receptor.

Alanine↗

Diabetes-associated mutations in insulin: consecutive residues in the B chain contact distinct domains of the insulin receptor.

How insulin binds to and activates the insulin receptor has long been the subject of speculation. Of particular interest are invariant phenylalanine residues at consecutive positions in the B chain (residues B24 and B25). Sites of mutation causing diabetes mellitus, these residues occupy opposite structural environments: Phe(B25) projects from the surface of insulin, whereas Phe(B24) packs against the core. Despite these differences, site-specific cross-linking suggests that each contacts the insulin receptor. Photoactivatable derivatives of insulin containing respective p-azidophenylalanine substitutions at positions B24 and B25 were synthesized in an engineered monomer (DKP-insulin). On ultraviolet irradiation each derivative cross-links efficiently to the receptor. Packing of Phe(B24) at the receptor interface (rather than against the core of the hormone) may require a conformational change in the B chain. Sites of cross-linking in the receptor were mapped to domains by Western blot. Remarkably, whereas B25 cross-links to the C-terminal domain of the alpha subunit in accord with previous studies (Kurose, T., et al. (1994) J. Biol. Chem. 269, 29190-29197), the probe at B24 cross-links to its N-terminal domain (the L1 beta-helix). Our results demonstrate that consecutive residues in insulin contact widely separated sequences in the receptor and in turn suggest a revised interpretation of electron-microscopic images of the complex. By tethering the N- and C-terminal domains of the extracellular alpha subunit, insulin is proposed to stabilize an active conformation of the disulfide-linked transmembrane tyrosine kinase.

Amino Acid Sequence↗

Safe major abdominal operations: hepatectomy, gastrectomy and pancreatoduodenectomy in elder patients.

AIM: To evaluate the impact of advanced age on outcome after hepatectomy, gastrectomy and pancreatoduodenectomy. METHODS: Two hundreds and eleven patients undergone hepatectomy, gastrectomy and pancreatoduodenectomy from January 1998 to September 2002 were analyzed retrospectively. Clinicopathologic features and operative outcome of 83 patients aged 65 years or more were compared with that in 128 younger patients aged less than 65 years. RESULTS: The nutritional state, such as pre-operation level of serum albumin and hemoglobin in the older patients was poorer than that in the younger patients. The older patients had higher comorbidities than the younger patients (48.2% vs 15.6%). No significant difference was observed in perioperative mortality, and complication rate between the older and younger patients (2.4% vs 1.6% and 22.9% vs 20.3%, respectively). Multivariate analysis demonstrated that pancreatoduodenectomy, hepatectomy with resection of more than 2 segments and comorbidities were independent predictors of postoperative complication, whereas age was not (P=0.3172). CONCLUSION: It is safe for patients aged 65 years or more to undergo hepatic, pancreatic and gastric resection if great care is taken during perioperative period.

Abdomen↗

[Effect of binding pancreaticojejunotomy in prevention of post-operational anastomotic leakage: a clinical study of 200 cases].

OBJECTIVE: To explore the effect of Peng's binding pancreaticojejunotomy (PBPJ) in prevention of pancreaticojejunal anastomotic leakage. METHODS: From 1996 to 2001, 200 patients, 139 males and 61 females, aged 32 approximately 80, with carcinomas of head of pancreas, ampulla, bile duct, duodenal papilla, descending partof duodenum, gallbladder, and body of pancreas, chronic pancreatitis, polyp of lower segment of bile duct, and gastric carcinomas that invaded the head of pancreas or recurred after operation, lithiasis of pancreatic duct, and islet cell carcinoma, underwent Peng's binding pancreaticojejunotomy, devised to prevent pancreaticojejunal anastomotic leakage from the needle holes of stoma, interspace between jejunal mucosa and pancreas, high pressure of jejunum, high tension and blood circulation deficiency of pancreaticojejunal stoma, etc. The clinical data were collected and analyzed. RESULTS: While the cut end of jejunum was sutured to the pancreatic remnant the needle only penetrated the jejunal mucosa without causing a needle hole on the surface of the stoma. After the remnant of pancreas was inserted into the jejunal cavity, a piece of cat gut was bound around the entire jejunal serous muscular sheath and the pancreatic remnant so as to make them stick to each other closely. No pancreatic leakage occurred among these 200 cases after operation. CONCLUSION: The PBPJ procedure can definitively avoid anastomotic leakage following pancreatoduodenectomy.

Adult↗

An RNA-binding domain in the thyroid hormone receptor enhances transcriptional activation.

Thyroid hormone plays important roles in development, differentiation, and metabolic homeostasis by binding to nuclear thyroid hormone receptors, which regulate target gene expression by interacting with DNA response elements and coregulatory proteins. We show that thyroid hormone receptors also are single-stranded RNA binding proteins and that this binding is functionally significant. By using a series of deletion mutants, a novel RNA-binding domain was localized to a 41-amino acid segment of thyroid hormone receptor alpha1 between the second zinc finger and the ligand-binding domain. This RNA-binding domain was necessary and sufficient for thyroid hormone receptor binding to the steroid receptor RNA activator (SRA). Although SRA does not bind directly to steroid receptors, it has been identified as a steroid receptor coactivator, and was thought not to be a coactivator for thyroid hormone receptors. However, transfection studies revealed that SRA enhances thyroid hormone induction of appropriate reporter genes and that the thyroid hormone receptor RNA-binding domain is important for this enhancement. We conclude that thyroid hormone receptors bind RNA through a novel domain and that the interaction of this domain with SRA, and perhaps other RNAs, enhances thyroid hormone receptor function.

Amino Acid Sequence↗

Doxycycline suppresses cerebral matrix metalloproteinase-9 and angiogenesis induced by focal hyperstimulation of vascular endothelial growth factor in a mouse model.

BACKGROUND AND PURPOSE: A number of central nervous system (CNS) disorders are associated with abnormalities in or activation of angiogenesis, including vascular malformations. To test the hypothesis that the nonspecific matrix metalloproteinase (MMP) inhibitor, doxycycline, suppresses vascular endothelial growth factor (VEGF)-induced cerebral angiogenesis through inhibition of MMPs, we used a mouse model with enhanced cerebral angiogenesis induced by focal hyperstimulation of VEGF from adenovirus DNA (AdVEGF) transduction. METHODS: The time course study of MMP activity was performed at 7 and 14 days after AdVEGF transduction. MMP activity and expression were examined by zymography and immunohistochemistry, respectively. As an index of cerebral angiogenesis, microvessel counting was performed in the brains of 3 groups of mice (n=6): (1) control; (2) AdVEGF only; and (3) AdVEGF plus doxycycline (30 mg/kg per day). RESULTS: Brain MMP-9 activities increased 4-fold (883+/-137 versus 179+/-179; 1-sided P<0.001) at 7 days after AdVEGF transduction. VEGF transduction increased vessel counts by 19% (255+/-27 versus 215+/-15, 1-sided P<0.01). Doxycycline treatment decreased MMP-9 activity (89+/-72 versus 883+/-137; 1-sided P<0.001) and cerebral microvessel number (231+/-17 versus 255+/-27; 1-sided P<0.05). CONCLUSIONS: Doxycycline is effective in decreasing stimulated cerebral MMP-9 activity and parenchymal angiogenesis. The decrease in MMP-9 activity is associated with decreased microvessel counts. Brain pathophysiological processes that involve abnormally enhanced angiogenesis may be amenable to manipulation by MMP inhibitors, including tetracycline derivatives.

Adenoviridae↗

[Role and significance of extrahepatic control of hepatic vein and inferior vena cava in difficult hepatectomies for patients with liver tumors].

OBJECTIVE: To explore the role of extrahepatic control on blood flow of hepatic vein and inferior vena cava in hepatectomy, and observe its effect on minimizing hemorrhage. METHODS: From 2001 to April 2003, 33 patients who had liver tumors involving segment IV, VII, VIII or half liver underwent major hepatectomies that required exposure of the inferior vena cava and main trunks of hepatic veins, during which the major hepatic veins and inferior vena cava were isolated and taped to control blood flow when necessary. RESULTS: In 33 attempts, 32 were successful and all tumors were resected successfully. The placement of occlusion tape was unsuccessful in 1 case. 7 cases did not need blood transfusion during operation. The amount of blood transfusion for other cases were form 0 to 1 600 ml. there was no operative mortality. CONCLUSIONS: Appropriate control of main truck of hepatic vein and inferior vena cava is effective in reducing blood loss during hepatectomies. It is also very helpful for performing difficult hepatectomies.

Adult↗

Hemangiopoietin, a novel human growth factor for the primitive cells of both hematopoietic and endothelial cell lineages.

The cells of hematopoietic and vascular endothelial cell lineages are believed to share a common precursor, termed hemangioblast. However, the existence of a growth factor acting relatively specifically on hemangioblasts remains unclear. Here we report the identification of hemangiopoietin (HAPO), a novel growth factor acting on both hematopoietic and endothelial cell lineages. In vitro in the human system, recombinant human HAPO (rhHAPO) significantly stimulated the proliferation and hematopoietic and/or endothelial differentiation of human bone marrow mononuclear cells and of purified CD34+, CD133+, kinase domain receptor-positive (KDR+), or CD34+/KDR+ cell populations. In the murine system, rhHAPO stimulated the proliferation of long-term culture-initiating cells (LTC-ICs) as well as CD34+ and stem cell antigen-1 (Sca-1+) cell subsets. In vivo, subcutaneous injection of rhHAPO into normal mice resulted in a significant increase in bone marrow hematopoietic cells. Furthermore, irradiated mice injected with rhHAPO had an enhanced survival rate and accelerated hematopoiesis. Our data suggest that HAPO is a novel growth factor acting on the primitive cells of both hematopoietic and endothelial cell lineages and that HAPO may have a clinical potential in the treatment of various cytopenias and radiation injury and in the expansion of hematopoietic and endothelial stem/progenitor cells.

Abortion, Spontaneous↗

[Therapeutic study of autologous Schwann cells' bridge graft into the brain of hemiparkinsonian monkey].

OBJECTIVE: To evaluate the therapeutic effect of autologous transplantation of Schwann cells as "bridge" between the medial forebrain bundle (MFB) and caudate nucleus, into the brain of hemiparkinsonian monkey. METHODS: Six monkeys were used following 6-OHDA-induced hemiparkinsonism. Three of them were autologous transplanted using Schwann cells as "bridges" between MFB and caudate nucleus. The Schwann cells were pre-treated using Hoechst33342. The other three monkeys received sham operation as controls. All the monkeys received behavioral assessment. The metabolism of dopamine was measured by SPECT using (99)Tcm-TRODAT-1 and PET using 18F-FP-beta-CIT. After a 4-month follow-up, the monkeys' brain were removed from the skull, fixed in 4% paraformaldehyde and cut into serial sections. A fluorescence microscope examination and a tyroxine hydroxylase (TH) immunohistochemistry study were made on the sections. Cell types were determined by double staining. The level of TH protein around the needle track was determined by Western blotting. RESULTS: All three monkeys, which had undergone Schwann cells autologous bridge graft showed a decrease in the disability score and two of them had an increase in motor activity. The apomorphine evoked rotation was also decreased. The symptoms of the monkeys, which received sham operation, had not amelioration. In SPECT examination, the radioactivity count was greatly increased in the grafted monkeys. The dopamine levels were significantly increased in the caudate nucleus from 61% (before graft) to 79% (after graft) while there's no change in control group. In histological examination, autologous Schwann cells could survive and migrate in the brain. Around the Schwann cells "bridge", there were numerous TH positive short fibers in the MFB area. Around the whole length of the "bridge", there were a lot of TH positive reactive astrocytes, especially in thalamus. TH protein around the needle track of the graft group was 243% compared with that of control group. CONCLUSION: Autologous Schwann cells bridge graft is a feasible technique with therapeutic effects on parkinson disease monkeys. The Schwann cells play an important role in dopaminergic axonal elongation and in inducing the TH positive phenotype of reactive astroglia cell around it.

Animals↗