Salidroside, the 8-O-beta-D-glucoside of tyrosol, is a novel adaptogenic drug extracted from the medicinal plant Rhodiola sachalinensis A. Bor. Due to the scarcity of R. sachalinensis and its low yield of salidroside, there is great interest in enhancing the production of salidroside by biotechnological process. Glucosylation of tyrosol is thought to be the final step in salidroside biosynthesis. In our related works, three UGT clones were isolated from the roots and the cultured cells. Our intention was to combine the catalytic specificity of these UGTs in vitro in order to change the level of salidroside in vivo by over-expression of the above UGTs. However, as the aglycone substrate of salidroside, the biosynthetic pathway of tyrosol and its regulation are less well understood. The results of related studies revealed that there are two different possibilities for the tyrosol biosynthetic pathway. One possibility is that tyrosol is produced from a p-coumaric acid precursor, which is derived mainly from phenylalanine. The second possibility is that the precursor of tyrosol might be tyramine, which is synthesized from tyrosine. Our previous work demonstrated that over-expression of the endogenous phenylalanine ammonia-lyase gene (PALrs1) and accumulation of p-coumaric acid did not facilitate tyrosol biosynthesis. In contrast, the data presented in our recent work provide in vitro and in vivo evidence that the tyrosine decarboxylase (RsTyrDC) is most likely to have an important function in the initial reaction of the salidroside biosynthesis pathway in R. Sachalinensis.
Genetic Engineering ; Glucosides ; biosynthesis ; Glycosylation ; Phenols ; Phenylethyl Alcohol ; analogs & derivatives ; chemistry ; metabolism ; Rhodiola ; metabolism ; Tyrosine ; metabolism ; Tyrosine Decarboxylase ; metabolism

Female ; Humans ; Male ; Myocardial Infarction ; drug therapy ; therapy ; Percutaneous Coronary Intervention ; methods ; Tyrosine ; analogs & derivatives

Acute Disease ; Humans ; Male ; Middle Aged ; Thrombocytopenia ; chemically induced ; Tyrosine ; adverse effects ; analogs & derivatives

Acute Coronary Syndrome ; drug therapy ; Angioplasty, Balloon, Coronary ; Aspirin ; administration & dosage ; Humans ; Platelet Aggregation Inhibitors ; administration & dosage ; Thrombelastography ; Ticlopidine ; administration & dosage ; analogs & derivatives ; Tyrosine ; administration & dosage ; analogs & derivatives

Minor fibrillar collagen types V and XI, are those less abundant than the fibrillar collagen types I, II and III. The alpha chains share a high degree of similarity with respect to protein sequence in all domains except the variable region. Genomic variation and, in some cases, extensive alternative splicing contribute to the unique sequence characteristics of the variable region. While unique expression patterns in tissues exist, the functions and biological relevance of the variable regions have not been elucidated. In this review, we summarize the existing knowledge about expression patterns and biological functions of the collagen types V and XI alpha chains. Analysis of biochemical similarities among the peptides encoded by each exon of the variable region suggests the potential for a shared function. The alternative splicing, conservation of biochemical characteristics in light of low sequence conservation, and evidence for intrinsic disorder, suggest modulation of binding events between the surface of collagen fibrils and surrounding extracellular molecules as a shared function.
Alternative Splicing ; genetics ; Animals ; Fibrillar Collagens ; chemistry ; genetics ; metabolism ; Humans ; Sulfates ; chemistry ; metabolism ; Surface Properties ; Tyrosine ; analogs & derivatives ; chemistry ; metabolism

Alveolar Epithelial Cells ; cytology ; metabolism ; Animals ; Apoptosis ; Lung ; drug effects ; metabolism ; Nitric Oxide ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Tyrosine ; analogs & derivatives ; metabolism

OBJECTIVETo observe the effect of nitrotyrosine on renal expressions of nuclear factor-κB (NF-κB), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-β1 (TGF-β1) in rats with diabetic nephropathy (DN).

METHODSRat DN models established by a single intraperitoneal injection of streptozotocin (STZ) were randomly allocated into model group, nitrotyrosine group and ebselen group, with untreated rats as the normal control group. The rats were given the corresponding drugs for 8 weeks, and after the last administration, the 24-h urinary protein level was measured and the kidneys of the rats were harvested for detecting the protein and mRNA expressions of NF-κB, MCP-1 and TGF-β1 with immunohistochemistry and RT-PCR, respectively. The pathological changes of the kidneys were assessed microscopically.

RESULTSCompared with those in the model group, the 24-h urinary protein level and expressions of NF-κB, MCP-1 and TGF-β1 mRNA and protein in the renal tissues were significantly increased by nitrotyrosine treatment, which also caused worsened renal pathology, while treatment with ebselen significantly ameliorated these changes.

CONCLUSIONNitrotyrosine can up-regulate the mRNA and protein expressions of NF-κB, MCP-1 and TGF-β1 and aggravate the inflammatory reaction in the renal tissue of DN rats to promote the progression of DN.

Animals ; Chemokine CCL2 ; metabolism ; Diabetes Mellitus, Experimental ; Diabetic Nephropathies ; metabolism ; Male ; NF-kappa B ; metabolism ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism ; Tyrosine ; analogs & derivatives ; pharmacology

OBJECTIVETo explore the feasibility of regulated expansion and committed differentiation potential of JAK2 gene modified hematopoietic stem/progenitor cells in vitro.

METHODSA murine stem cell virus (MSCV) based retroviral vector MGI-F2Jak2, which encodes a green fluorescent protein (GFP) and a fusion protein containing two copies of modified FK506 binding protein (F36v) linked tyrosine kinase JAK2 was cloned. F36v served as a high-affinity binding site for dimerizer AP20187. GpE + 86 packaging cell was transfected with this vector. Bone marrow cells from C57BL/6 mice were transduced by co-cultured with irradiated (1500 cGy) GpE + 86 producer clone for 48 h. Transduced marrow cells were expanded in X-VIVO 15 and divided into four groups as follows: (1) control group; (2) AP20187 alone group; (3) SCF alone group and (4) AP20187 + SCF group. The phenotypes of the expanded cells were analyzed by directly phycoerythrin-labeled anti-Sca1, c-kit, CD(34), Gr1, CD(11b), TER119, CD(41), B220 and CD(3) monoclonal antibodies for flow cytometry. Committed differentiation, progenitor colony assay and spleen colony forming units (CFU-S) were further evaluated.

RESULTSA significant sustained outgrowth of transduced marrow cells was obtained only in the AP20187 + SCF group. Cells expanded up to 10(14)-fold after 80 days culture. The doubling time was about 30 hs. The phenotypes of the expanded cells were homogeneously strong positive for CD(34), c-kit and Sca1, while were almost negative for Gr1, CD(11b), TER119, CD(41), B220 and CD(3). Functional assay demonstrated that the expanded cells had multipotential to differentiate into granulocyte, macrophage, erythrocyte, or B-cells under different cytokines combinations. A prominent megakaryocytic differentiation was observed when cultured with SCF/Tpo/IL-11 combination. The expanded cells were also capable of forming BFU-E, CFU-GM and CFU-Mix in methylcellulose colony assay. The expanded cells over three months could still form CFU-S.

CONCLUSIONSAP20187 combined SCF mediated activation of JAK2 signaling domain can dramatically expand hematopoietic stem/progenitor cells, and the expanded cells can be regulated and committed to differentiate into multilineage cells. This system may provide important insights into stem cell biology and may be promising for gene and cell therapy.

Animals ; Cell Differentiation ; Female ; Hematopoietic Stem Cells ; cytology ; Janus Kinase 2 ; Mice ; Mice, Inbred C57BL ; Protein-Tyrosine Kinases ; genetics ; physiology ; Proto-Oncogene Proteins ; Tacrolimus ; analogs & derivatives ; pharmacology ; Transfection

Angioplasty, Balloon, Coronary ; methods ; Humans ; Myocardial Infarction ; therapy ; Platelet Aggregation Inhibitors ; administration & dosage ; therapeutic use ; Tyrosine ; administration & dosage ; analogs & derivatives ; therapeutic use

BACKGROUNDTransradial access has been increasingly used during primary percutaneous coronary intervention (PCI) for patients with acute ST-segment elevation myocardial infarction (STEMI) in last decade. Clinical benefits of upstream use of tirfiban therapy in STEMI patients treated by primary PCI have been reported. We investigated the merits of transradial vs. transfemoral access in primary PCI for STEMI patients with upstream use of tirofiban.

METHODSPatients with STEMI treated with tirofiban between December 2006 and October 2012 then by primary PCI were compared between transradial (n = 298) and transfemoral (n = 314) access. Baseline demographics, angiographic and PCI features and primary endpoint of major adverse cardiac events (MACE) at 30-day clinical follow-up were recorded.

RESULTSBaseline and procedural characteristics were comparable between the two groups, apart from more patients in transradial group had hypertension and were treated by thrombus aspiration during primary PCI. Significantly fewer MACE occurred in the transradial group (5.4%) compared with the transfemoral group (9.9%) at 30-day clinical follow-up. Major bleeding events at 30-day clinical follow-up were 0 in transradial group and in 2.9% of transfemoral group. Multivariate analysis confirmed transradial approach as an independent negative predictor of 30-day MACE (HR 0.68; 95%CI 0.35 - 0.91; P = 0.03).

CONCLUSIONSUsing transradial approach in primary PCI for acute STEMI infarction patients treated with tirofiban was clearly beneficial in reducing bleeding complications and improving 30-day clinical outcomes.

Aged ; Angioplasty, Balloon, Coronary ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; therapy ; Percutaneous Coronary Intervention ; methods ; Tyrosine ; analogs & derivatives ; therapeutic use