January 04, 2013

Important association of estrogen receptor binding site variation women with bipolar disorder.

Depression is two times of women compared with men. In bipolar disorder, depressive episodes in female patients reported more common. In addition, depression often and hormonal fluctuations period. Hormone signal connection between these emotional obstacles, therefore, is considered in many studies. Estrogen, a major female hormone, and its effect mainly by binding to estrogen receptors (ERs). Nuclear ers function as a transcription factor and regulating gene transcription is bound to a specific DNA sequence. A nucleotide changes may change the binding of binding sequence efficiency, this may affect the adjacent gene transcription level. To investigate if the variable ER DNA binding sequence may be involved in emotional obstacles, we performed a genome-wide research the patient's ER DNA binding diagnosed with depression or bipolar disorder. Association study in each gender separately, the result is more than the correct Bonferroni test method. In the women's bipolar affective disorder material significant results are found rs6023059 association (correction p-value = 0.023; odds ratio (or 0.681, 95% confidence interval (CI) 0.570-0.814), a single nucleotide polymorphisms (SNPS) placed tream genes encoding transglutaminase 2 (TGM2). Therefore, women with a specific genotype in the SNP may be more prone to fluctuation of estrogen level, which can act as a trigger factors on bipolar affective disorder.

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Function characteristics of naturally occurring transglutaminase 2 mutant and early onset of type 2 diabetes.

Transglutaminase 2 (TG2) is a kind o enzyme and different biological function. Transamidation TG2 catalytic reaction, has intrinsic kinase activity, and ACTS as a g protein within the cell signal. TG2 (Tgm2) null mice blood glucose intolerance, damaged biology insulin secretion (GSIS). In addition, three naturally occurring missense mutation, gene in human TGM2 corresponding Met330Arg amino acid substitutions, Ile331Asn, Asn333Ser TG2 in protein, report and found to be related to the type 2 diabetes and early onset. However, their influence is still not fully understand TG2 function. In order to prove this point, we have again naturally occurring mutation site-directed mutagenesis TG2 use. In the INS - 1 e express Myc - TG2 mutant cells leads to reduce GSIS and cell excessive expression compared with wild type Myc - TG2 (WT - TG2). The biggest decrease was found in cell excessive express Ile331Asn - TG2 (32%), the second is Met330Arg - TG2 (20%), at least in the Asn333Ser - TG2 (7%). Enzyme analysis suggests that transamidation TG2 mutant damaged and kinase activity and WT - TG2 compared. Tests show the GTP binding TG2 mutant also changed the GTP binding ability, it is found that modulation response glucose stimulation. In general, these data show that naturally occurring mutations affecting the transamidation TG2, kinase, GTP binding TG2 function. Although reduce insulin secretion, because naturally occurring mutations, is due to TG2 detract from more than one biological function, it is transamidation TG2 function, it seems to be in the first stage is impaired, and GTP binding function will affect the second stage of insulin secretion.


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Transglutaminase 2 and the nf-kappa B: a strange couples, shape breast cancer phenotype.

Because many professional survival target genes, abnormal activation of the nf-kappa B transcription factor is a kind of drug resistance phenotypic correlation and aggressive breast cancer behavior. 


, a ubiquitously expressed protein crosslinking enzyme, activate the nf-kappa B through the unconventional mechanism, disable I κ B α inhibitors. Our company recently records, TG2 genes (known as TGM2) is a direct nf-kappa B transcription goal. These development uncover a self-enforcing molecular feedback loop, novel nf-kappa B TG2 activation, in turn, the nf-kappa B direct upregulates TGM2 transcription. The manuscript of the literature review, support are TG2 / nf-kappa B signal cycle, nature of the signal transduction, activate the circulation, and phenotypic consequences from abnormal activation of the novel signal mechanism in breast cancer

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January 03, 2013

Branch geometric induced lung automatic adjustment of growth.

Branch morphogenesis is a widely distributed in natural phenomenon. In organogenesis, which results in uneven growth, leading to the epithelium single branch into the surrounding mesoderm repeat. Lung morphogenesis is a landmark case, tree organogenesis the most common mammals. The core network is very sure, especially Fgf10 / SHH couples, need to start and the maintenance branch. In the previous study, we show that limit Fgf10 expression domain hiss distal interstitial spontaneously entice differential epithelial hyperplasia lead to branch. A simple Laplacian model copy FGF10 qualitative dynamic interstitial and spontaneous self avoid branch morphogenesis. However, the early lung cancer geometry several conspicuous features, remain to be resolved. In this paper, we mainly research, through the simulation and analysis of data, if FGF10 - diffusion in the scene of the following aspects of the lung morphology: size dispersion, asymmetric branch events and distal epithelium mesothelium balance. We report said, they appear in the model of spontaneous, and most of the bottom mechanism can be understood as dynamic gradient and the interaction between the shape. This shows that the specific provisions may not need these emergent compelling geometrical characteristic

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Teeth agenesis association claims to have a family history of cancer.

It has been put forward, the tooth agenesis and cancer development has a common molecular pathways. We conducted a cross-sectional study survey of molecular epidemiology and the correlation between and readme teeth agenesis of the cancer family history. Eighty-two people with tooth agenesis and 328 people do not have the same institution of recruiting birth defects. Teeth dysplasia is evaluation in permanent teeth and definition based on participants' age, when the initial form teeth should radiology visible. We also investigated the action of the genes involved in dental development involved in tumorigenesis and 14 mark, FGF3 AXIN2, FGF10, FGFR2 were genotyped. Teeth agenesis people have greater risks have a family history of cancer (p = 0.00006; or = 2.7; 95% ci, 1.6 to 4.4). A connection between AXIN2, FGF3, FGF10, and teeth agenesis (or FGFR2. Personal carry polymorphism allelic FGFR2 (rs1219648) puts forward higher risk have premolar hypoplasia (p = 0.02; or = 1.8; 95% ci, 1.1-3.0)]. In a word, the tooth dysplasia is and positive self report of cancer family history and variant in AXIN2, FGF3,FGF10, FGFR2. Prospective study is needed to confirm if the teeth agenesis can be used as a risk marker for cancer.

more...

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imulation demonstrates a simple network enough to control branch point selection, vascular smooth muscle and the formation of the system in the lung branch morphogenesis.

Appropriate lung function not only need a proper structure of conductive airway tree, but also the development of the smooth muscles and blood vessels. Lung branch morphogenesis strong rigidity and includes recursive use only three kinds of modes of the branch. We've confirmed that the interaction between the description fibroblast growth factor (FGF) 10, sonic hedgehog (SHH) and repair (Ptc) can produce a Turing machine system, not only breeding experimental observation to the wild type branching pattern, part of the reason is counterintuitive, pattern in the mutant mice. Here we show that although many protein influence the formation of smooth muscle and Vegfa expression, an inducer formation of blood vessels, it is enough to FGF9 added to the FGF10 / boo/Ptc module successfully predicted at the same time appear smooth muscle growth between crystallization, Vegfa lung bud expression in the distal joint epithelial cells stroma. Our model reproduces the phenotype, and related mutant mice wild type, and most of the culture conditions described in the literature

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December 11, 2012

Methyl mercury cause the nf-kappa B CCL2 expression through the activation in human 1321 n1 astrocytes

Methyl mercury is an environmental pollutant, poisonous central nervous system; However, its toxic molecules mechanism is not clear. Methyl mercury increase several chemokine expression in cerebellar mice and methyl mercury. This study analyzed the potential of the methyl mercury induced chemokine expression mechanism use human 1321 n1 astrocytes, and display, methyl mercury increases in these cells CCL2 expression. The transcription factor nf-kappa B is involved in induced chemokine expression. Methyl mercury levels increase the nf-kappa B p65 subelement in the nuclei of 1321 n1 cell. Methyl mercury cause increase significantly reduce the CCL2 expression inhibition p65 expression by RNA interference. The results show that methyl mercury cause the nf-kappa B chemokine expression through the activation in human astrocytes

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Serum level of CC chemokine CCL2, CCL5, CCL11 food allergy in children with different clinical manifestations.

Food allergy (FA) is frequent in 8% of children under 3 years old and about 2% of adults. Chemokine is involved in all kinds of allergies such as fa. The purpose of this study is to determine the CCL2, CCL5, CCL11 level in the fa cup. The study population cross-sectional study contains 63 patients suffering from the fa cup and 100 healthy controls. The concentration of the CCL2, CCL5, CCL11, IgE measurement using enzyme-linked immunosorbent assay (ELISA). Use Kathy Ι eosinophils number cell count + analyzer system model SCAREF system GmbH. Is considered to be an important difference, P < 0.05. The results show that the number of FA patients significantly increased than cycle without disease control peripheral eosinophil. The fa patients serum immunoglobulin e level is higher than the control. We also show that serum CCL2 and CCL11 was significant increase in the fa, but compared with patients who CCL5 not detectable control. The results of this study showed that two CCL11 CCL2, more elevated FA children with allergic reaction and urticaria than bronchial asthma and allergic dermatitis. These results also show that more level of increase and CCL11 CCL2 observation after consumption of milk and pistachios. Overall, the results suggest that serum CCL2 and CCL11 rise FA and these may be considered useful parameters in the diagnosis of the disorder. Still can design treatment on the basis of, through the application block chemokine expression antibody they overcome allergic patients with complications in the fa.

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Allelic gene expression cattle IGF2 imbalances, mineral wax and the CCL2 genes in liver, kidney and pituitary.

Allele expression imbalance (AEI) is a kind of important genetic factor is the difference of the phenotypic traits, can genetic. The study can be used to find factors that regulate gene expression molecular mechanism, which is helpful to understand the bottom phenotypic change. Although it is generally accepted in many species, and we know that many genes show allele expression imbalance, this kind of phenomenon is not large scale study in cattle. Use pyrophosphoric acid sequencing technology method we analyzed a group of 29 cattle genes in order to find the favorable allele expression. The study investigated in three organization: liver, pituitary and kindey. From the research group of genes and their mineral wax (leptin), IGF2 (insulin-like growth factor 2), the CCL2 (chemokine carbon-carbon bond pattern ligand 2) display allelic expression is not balanced.

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December 06, 2012

Increase can activate thrombin inhibitor in hypothyroidism and hyperthyroxinaemia fibrinolysis.

Endocrine disorders that affect coagulation and fibrinolysis system and related the development of cardiovascular disease. Thrombin increase can activate fibrinolysis inhibitors (TAFI) is a link between coagulation and fibrinolysis system. The purpose of this study was to determine the effect of thyroid hormone excess and lack of in TAFI level and function. In TAFI hyperthyroxinemia was studied in healthy volunteers were randomly assigned to accept left-hand thyroid hormone or no drug treatment for 14 days in crossover design. In TAFI hypothyroidism was studied in a multi-center observational cohort study. Pumping blood therapy patients before, when euthyroidism newly diagnosed the hypothyroidism. Plasma clot dissolution time, activation TAFI (tower Philippines and wine) depend on the extended blood clot dissolved and TAFI level measurement. Thyroid hormone excess lead to hypofibrinolytic conditions and in an enhanced tower Philippines and alcohol dependence extended blood clot dissolved. The trend of decline TAFI observation plasma levels in healthy volunteers use left-hand thyroid hormone. Hypothyroidism cause hyperfibrinolysis and reduce the tower Philippines and alcohol dependence extended blood clot dissolved. In a word, the change of the tower Philippines and alcohol dependence extended blood clot dissolved in patients with thyroid disease may lead to a damaged hemostatic balance. In the disturbance hemostatic patients balance hyperthyroidism may make them easy to thrombosis, and the risk of bleeding may increase patient hypothyroidism.

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Allosteric network in the thrombin procoagulant and anticoagulant activity to distinguish.

Alpha thrombin of serine protease is a kind of protein, can be used as the blood coagulation cascade. Thrombinprocoagulant itself is a differences, fibrinogen make fibrin clot, but thrombin - thrombomodulin (TM) complicated start anticoagulation path, through the crack protein c. TM fragment of only the fifth and sixth egf like domain (TM56) enough to bind thrombin, but there are also the fourth egf like domain (TM456) induced vital anticoagulant activity of thrombin. Crystallography of thrombin - TM456 complex and not found in the thrombin bring significant structural change, this shows that TM4 may only provide a scaffold best calibration of protein C for the cleavage, thrombin. However, all kinds of experimental data show that exist TM4 may affect the dynamic properties of the active site cycle. In the present work, we use two traditional and accelerate the molecular dynamics simulation method is used to study the dynamic characteristics of the structure, thrombin of thrombin: TM56, thrombin: TM456 in a wide range of time scales. Two different but related allosteric way, while determining mediation pro - and anticoagulant blood clotting enzyme activity. A allosteric way, at the same time, present in the thrombin: TM56 and blood coagulation enzyme: TM456, direct connection TM5 domain of thrombin active site. Other allosteric path, which only appears in the slow time scale exist TM4 domain, including prolong the network related action connection TM4 and TM5 domain and active site cycle of thrombin.

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Clotting enzyme activities in space propagation in clotting as excitation wave.

Traumatic hemorrhage is stopped by a hemostatic plug formation, is from a complicated nonlinear and space heterogeneous network proteolytic enzyme biochemical called blood coagulation. We study the spatial dynamic thrombin, the enzyme this network, by developing a fluorogenic substrate to establish methods and space to solve imaging time,thrombin enzyme activity. Clotting stimulation, immobilized tissue factor induced localized clotting enzyme activities of the impulse, in space propagation, have all the characteristics of a tourist excitation wave: constant space velocity, constant amplitude and ignore the initial stimulus once more than activation threshold value. This wave parameters by phospholipid availability or platelet, wave not form in the plasma from type A hemophiliac factors or C lack of viii and XI, the two main mediators condensation positive feedback. Stimulation of the negative feedback of protein C ways and thrombomodulin produce nonstationary model of wave form followed by reduction and destruction. This suggests that the blood can be used as an emotional media, in tourism wave after wave of solidification.

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November 26, 2012

No compensation VEGF expression follow antisense inhibition BCL 2 activities

Antisense oligonucleotides (management) has been used for prostate cancer model for growth regulatory proteins, and at least one oligosaccharides (against BCL  has reached the clinical test. We've found that in LNCaP cell, mono - and double function management, the relative inhibitory expression, as compensation, the base class library 2 inhibition caspase 3 (apoptosis promoter) activities, and increase the expression of androgen receptor (AR) and p300 and il - co catalyst. In addition, the prostate specific membrane antigen (PSMA) and (may be its regulators) interferon (IFN) rise. 14 protein distributed between regulators of apoptosis, androgen control, differentiation antigen and autocrine mediated growth has been inspection. We put these findings including vascular endothelial growth factor (VEGF), promote angiogenesis, not through the compensation significant change, so do not need additional supervision for repression BCL 2 treatment is effective (such as caspase 3).

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Apoptotic cell death Trichostatin a inductive hella cells in BCL 2 and oxidative stress depend on the way.

Trichostatin (TSA) as a reason inhibitor can adjust many biological properties including the cell apoptosis and cell proliferation in all kinds of cancer cells. Here, we evaluate the effects of TSA in growth and death sheila cervical cancer cells and reactive oxygen species (ROS) and glutathione (GSH) content. Dose - and the time to observe somatostatin in hella cells and a IC50 about 20 nM 72 h. The agency also induced apoptosis cells die, as annexin v bovine serum albumin dyed cells, caspase 3 activation and the loss of mitochondrial membrane potential (MMP; ∆ ψ m). In addition, the government of the base class library 2 small interference RNA aggravate tsa induced hela cell death. All the testing caspase inhibitor greatly save some cell tsa induced hela cell death. TSA increased, O2 - level and inducing glutathione hella cell. Caspase inhibitor decreased obviously, O2 - level, GSH hella cell tsa treatment. In addition, n-acetyl cysteine (NAC; a known antioxidant) significantly prevent cell death and glutathione tsa treatment of hella cells, by reducing the O2 - level. In short, TSA cytostatic sheila through the BCL 2 mediated apoptosis closely related, O2,, glutathione levels.

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Clusterin awarded anti TNF α induce cell apoptosis in the breast cancer cells through the NF - kappaB activation and BCL 2 overexpression

Secretion clusterin (sClu) is a kind of disease of protein, played an important role in protecting cells from tumor necrosis factor (TNF) α induced apoptosis. The purpose of this study was to survey the molecular mechanism of the influence sClu TNF induced apoptosis in breast cancer cells. The wild type of p53 expression MCF 7 cell line was designed out excessive performance sClu (MCF 7 / sClu), and mda - m - 231 cell line and mutant p53 and sClu son transfection is the silence of the small interference RNA (mda - m - 231 / sClu small interference RNA). Clusterin overexpression influence, in the cell apoptosis and sensitivity are two TNF α in vitro. Our results show that TNF treatment increase BCL 2 mRNA and protein content in breast cancer cells, which suggests that BCL 2 directly subject to nuclear factor - kappaB (NF - kappaB) in response to TNF α. The induction of the base class library 2 mediated p65 subelement of NF - kappaB. The silence of the small interference RNA mediated BCL 2 lead to increased significantly TNF induced apoptosis. The silence of the sClu in mda - m - 231 / sClu small interference RNA cell abolished TNF mediated NF - kappaB activation and BCL 2 overexpression, and present mda - m - 231 / sClu small interference RNA cell significantly more sensitive, TNF than parent mediated apoptosis. In addition, sClu expression in the MCF 7 / sClu cell mediated TNF NF - kappaB promotion activities and BCL 2 overexpression, and presents MCF 7 / Clu cell significant resistance to TNF α mediated apoptosis. Inhibition of NF - kappaB activity or p65 and BCL 2 expression reverse these effects. The results show that sClu awarded breast cancer cells apoptosis induced resistance of TNF α by NF - kappaB activation and BCL 2 overexpression.

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November 18, 2012

Shrimp invertebrates lysozyme I - lyz: gene structure, molecular model and the response of the c and I renaturation to lipopolysaccharide (LPS)

Invertebrate lysozyme (I - lyz or destabilase) exist in shrimp. The protein may have a function as a peptidoglycan break enzyme and as a peptide enzyme. Shrimp usually vibrio infection. , gram negative bacteria, as is known to all, c - lyz (similar to the chicken lysozyme) is active against these bacteria. In order to further understand renaturation of rules, we determine the sequences of genes and protein structure I - lyz modeling. In addition, I - lyz expression and c - lyz response lipopolysaccharide (LPS) was studied. Shrimp I - lyz gene is made up of two introns interrupt to standardize joint connection. Expression of shrimp I - lyz is transient cut injection followed by after LPS induced after 6 hours in hepatopancreas. By contrast, c - lyz is raised hepatopancreas 4 h post injection and trimmed in gill. L. vannamei I - lyz does not contain of lysozyme catalytic residues (glycohydrolase) is not isopeptidase activities; However, as is known to all, antibacterial activities not only rely on the enzyme activity of protein. Research invertebrates lysozyme will increase our understanding of the regulatory process defense mechanism.

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The Lysozyme immobilized of micro-sized magnetic particles

In order to use lysozyme as an antimicrobial agent in the brewing process, the hen protein lysozyme (LYZ) is in two different covalent immobilization micro size magnetic particle (toluene sulfonyl activation and carboxylated, TSA and CA, respectively). A cell suspension of Oenococcus oeni, a oenological strain to participate in brewing process, be used as LYZ substrate. At the same time, a research dynamics study the stability of a LYZ free and fixed in the McIlvane buffer in the pH value is 3.2, the lowest pH value in wine. Activities and dynamics parameter measuring free LYZ pH value is 3.2, below reported in the best pH value (4.5); However residual activity in the pH value 3.2 is enough interests for further fixed and applications in the wine. All the dynamics parameters two biological catalyst (LYZ - CA and LYZ - TSA) after fixed change, this may be due to the active site structure modification caused by covalent attachment support. At 25 ° C is free the half-life of calculation LYZ 39 h, but it increases to 280 and 134 h and LYZ - CA LYZ - TSA of respectively. The results show that the stability of the immobilized enzyme and improve, can use LYZ in wine application in its fixed form. In addition, LYZ - TSA seems to be the best biological catalyst for further application in wine.

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Human serum albumin-coated gold nanoparticles for selective extraction of lysozyme

The study describes the use of selective high PI protein extraction and enrichment of human serum albumin (HSA) modified gold nanoparticles (HSA-AuNPs), lysozyme (LYZ) prior to analysis by capillary electrophoresis (CE)with UV detection. HSA gold nanoparticles can be extracted from a complex matrix LYZ HSA the caprock not only stable gold nanoparticles in high salt environment, but also showed a strong electrostatic attraction LYZ neutral pH conditions. LYZ and other high isoelectric point (pI) of the efficient separation of the protein has been successfully achieved by the cationic polyelectrolyte, poly (dimethyl diallyl ammonium chloride the) (PDDAC) filling, background electrolyte. Capture and HSA-AuNPs LYZ PDDAC filled CE can be directly used for analysis of the extracted LYZ releasing agent is not added to the extractor. Extraction efficiency depends on the gold nanoparticles of the solution pH and concentration of HSA. In the preferred extraction conditions, the signal-to-noise ratio of the detection limit of 3 LYZ of 8nm or less. HSA-AuNPs extraction and PDDAC of a combination of filling the CE has been the application of the analysis LYZ egg white, human milk, and the human tear. In addition, based on the extraction of the NP may be coupled to matrix-assisted desorption / ionization time-of-flight mass spectrometry and sodium dodecyl sulfate - polyacrylamide gel electrophoresis

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September 14, 2012

Anchored proteins that can affect the body's the Portuguese sugar metabolism and insulin secretion

Recently, scientists from the United States and Sweden, through the study found a new control point (a kinase anchoring proteins), and this may help provide for the treatment of diabetes or certain metabolic diseases. A kinase anchoring proteins, or AKAPs is known to affect a protein the cellular kinase dimensional dispersion, of course, this protein is also the control and the body's blood sugar regulation related to one of the important events enzymes.

The study, published in the internationally renowned magazine The EMBO Journal, researchers for the first time reveals AKAPs spatial orientation through the coordination of phosphate enzyme to influence the body's blood sugar levels phosphatase is a naturally occurring enzymes, can the effect brought by the neutralization and kinase. Researchers said John Scott, our findings reveal the contribution of the anchoring enzymes for cells regulate events, which may help us to seek rapid treatment of diabetes or metabolic disease therapies. Findings reveal AKAP 150 anchor role protein plays in the control of glucose metabolism and related metabolic disorders, post-anchored proteins, we can target to design new drugs to interfere with its function, to treat disease.

The researchers used imaging technology and the insulin-secreting cells separating genetic modification technology by mouse study, to investigate the anchoring protein for the mouse glucose metabolism and insulin release effects. The study found that lack of encoding AKAP 150 anchor protein gene in mice will produce less insulin in the islet area, however, researchers good handle due to the lack of target tissue in skeletal muscle insulin sensitivity increase triggered insulin secretion in mice The results show that these effects are caused due to the 7 amino acid sequence in the anchor protein can interact directly with the surface of phosphatase.

The release of insulin is the principal means of regulating the glucose level of the body. In the future, we may develop new drug targets this seven amino acid sequence region, directly phosphatase role, if you can, this will improve in the the selective tissue such as skeletal muscle insulin sensitivity . The study shows a molecular control point is very clear for us, this may provide some idea of ​​the clinical treatment of diabetes or certain metabolic diseases.



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September 11, 2012

Mouse embryonic cells in FGF21 fibroblast Growth factor 21: the next antidiabetic drug?

Fibroblast growth factor (FGF) is a class of more than 20 members of the cytokine family, has a variety of physiological functions to promote cell proliferation, body development, angiogenesis, wound repair. Different ways, mainly through local role in most FGF, FGF-19, FGF21 fibroblast Growth factor 21 and FGF-23 showed endocrine factor activity in metabolic regulation process, thanks to the fracture of the β-clover area it has a weak heparin-binding ability, and helps to spread to other sites to play a role. FGF-21 plays an important role in the regulation of glucose and lipid metabolism in the ascendant, it is expected to become a clinical drug for the treatment of type 2 diabetes.

FGF-21 in metabolic diseases is becoming the academia the new hot spot. Since 2005, doubling year after year, the number of research papers on the FGF-21FGF21 fibroblast Growth factor 21, but the understanding of its mechanism of action is still in its infancy. Many basic scientific questions remain to be answered. There are several different forms of FGF-21 is in the early stages of clinical research, FGF-21 in vitro studies of the structure and function has also made ​​great progress, and of FGF-21 pharmacological effects in animal tests showed good consistency and repeatability. More importantly, the test has been confirmed the TZD can affect FGF21 fibroblast Growth factor 21 and its receptor expression, indicating that such drugs may partially through FGF-21 signaling pathway, anti-diabetic effect. In addition, although the pharmacological effects of FGF-21 is powerful, but some animals may be presence of FGF21 fibroblast Growth factor 21 resistance, and therefore to develop more potent agonist FGF-21 will help to overcome the potential of FGF-21 resistance. Ongoing clinical trials, and the deepening of the basic research for the development on metabolic disease have therapeutic value FGF-21 agonists provide a reliable basis.

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