Biomedical subjects
Publications and source records attributed to Yuan Ji.
The activity of the eukaryotic OMEGA-Fanzor genome editing system remains limited in plants. We engineered the Fanzor nucleases SpuFz1, GtFz1, NlovFz2, and MmeFz2 in plants, with NlovFz2 being the most efficient, achieving up to 50.0% editing in regenerated rice plants, making it a promising tool for plant genome editing.
Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.
AIM: To recognize cystic neoplasia of the pancreas and thus to identify a panel of curable diseases. METHODS: Sixty-four cases of cystic neoplasia of the pancreas, including 28 cases of intraductal papillary mucinous neoplasia (IPMN), 12 cases of serous cystic neoplasia (SCN), 11 cases of mucinous cystic neoplasia (MCN), 11 cases of solid pseudo-papillary neoplasia (SPN), and 2 cases of solid tumor with cystic degeneration were examined immunohistochemically for their expression of MUC1, MUC2, MUC4, MUC5AC, and MUC6, as well as other related antigens. RESULTS: Adenoma type of IPMN and borderline lesions exhibited high expressions of MUC2, and MUC5AC. In contrast, IPMN with invasive carcinoma component showed MUC1 immunoreactivity. SCN was mainly positive for MUC1 and MUC6, while negative for MUC2, MUC4 and MUC5AC. Noninvasive MCN, regardless of its cellular atypia degree, was positive for MUC5AC and negative for MUC1. MUC1 expression was only observed in patients with an invasive component. No mucin expression was found in SPN. CONCLUSION: Mucin profile may, in conjunction with histologic study, provide important information on tumor types and patient treatment of cystic neoplasia of the pancreas.
We describe the fabrication and characterization of tungsten oxide nanofibers using the electrospinning technique and sol-gel chemistry. Tungsten isopropoxide sol-gel precursor was incorporated into poly(vinyl acetate)(PVAc)/DMF solutions and electrospun to form composite nanofibers. The as-spun composite nanofibers were subsequently calcinated to obtain pure tungsten oxide nanofibers with controllable diameters of around 100 nm. SEM and TEM were utilized to investigate the structure and morphology of tungsten oxide nanofibers before and after calcination. The relationship between solution concentration and ceramic nanofiber morphology has been studied. A synchrotron-based in situ XRD method was employed to study the dynamic structure evolution of the tungsten oxide nanofibers during the calcination process. It has been shown that the as-prepared tungsten oxide ceramic nanofibers have a quick response to ammonia with various concentrations, suggesting potential applications of the electrospun tungsten oxide nanofibers as a sensor material for gas detection.
A facile fabrication of a cross-linked hyaluronic acid (HA) hydrogel nanofibers by a reactive electrospinning method is described. A thiolated HA derivative, 3,3'-dithiobis(propanoic dihydrazide)-modified HA (HA-DTPH), and poly(ethylene glycol) diacrylate (PEGDA) are selected as the cross-linking system. The cross-linking reaction occurs simultaneously during the electrospinning process using a dual-syringe mixing technique. Poly(ethylene oxide) (PEO) is added into the spinning solution as a viscosity modifier to facilitate the fiber formation and is selectively removed with water after the electrospinning process. The nanofibrous structure of the electrospun HA scaffold is well preserved after hydration with an average fiber diameter of 110 nm. A cell morphology study on fibronectin (FN)-adsorbed HA nanofibrous scaffolds shows that the NIH 3T3 fibroblasts migrate into the scaffold through the nanofibrous network, and demonstrate an elaborate three-dimensional dendritic morphology within the scaffold, which reflects the dimensions of the electrospun HA nanofibers. These results suggest the application of electrospun HA nanofibrous scaffolds as a potential material for wound healing and tissue regeneration. [image: see text] Laser scanning confocal microscopy demonstrates that the NIH3T3 fibroblast develops an extended 3D dendritic morphology within the fibronectin-adsorbed electrospun HA nanofibrous scaffold.
AIM: Recently it has been reported that granulocyte colony stimulating factor (G-CSF) can induce hypercoagulability in healthy bone marrow donors. It is conceivable that the induction of a prothrombotic state in a recipient of an organ graft with already impaired perfusion might cause further deterioration in the transplanted organ. This study evaluated whether G-CSF treatment worsens liver perfusion following liver transplantation in the rat model. METHODS: A non-arterialized rat liver transplantation model was employed to evaluate the effect of G-CSF treatment on the liver in a syngeneic and allogeneic strain combination. Study outcomes included survival time and liver damage as investigated by liver enzymes and liver histology. Observation times were 1 d, 1 wk and 12 wk. RESULTS: Rats treated with G-CSF had increased incidence and severity of biliary damage following liver transplantation. In these animals, hepatocellular necrosis was accentuated in the centrilobular region. These lesions are indicative of impaired perfusion in G-CSF treated animals. CONCLUSION: G-CSF should be used with caution in recipients of liver transplantation, as treatment might enhance preexisting, undetected perfusion problems and ultimately lead to ischemia induced biliary complications.
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We demonstrate that electrophoresis on a flat Si substrate is an effective method in separation of DNA with different configurations, e.g., linear, supercoiled, and relaxed or DNA of different length, e.g., supercoiled DNA ladder. The surface separation arises from the different number of contacts due to the conformational differences between adsorbed DNA chains. Imposing a Au nanopattern on the Si surface further improves the separation effect. The simulation of electric field on this patterned surface by the finite element method shows that Au nanodots act as local pinning points for DNA segments due to dielectrophoretic force. The results of molecular dynamics simulation showed that the conformational differences between adsorbed polymer chains were amplified on the patterned surface and enhanced separations were achieved, which are consistent with the experimental results.
BACKGROUND: Despite the newly discovered plasticity of hematopoietic stem cells, their capacity to "transdifferentiate" into parenchymal cells and the regulation of this process is not yet elucidated. The present study was designed to investigate the effect of stem cell mobilization and liver regeneration on this process using a syngeneic rat female-to-male liver transplantation model. METHODS: Rate and frequency of Y-chromosome containing hepatocytes was determined by fluorescence-in situ hybridization (FISH) using a rat Y-chromosome specific probe. Rats were subjected to full-size or partial liver transplantation with and without stem cell mobilization using granulocyte colony stimulating factor (G-CSF). The effect of stem cell mobilization was confirmed by assessing the white blood count and by evaluating the migration of granulopoietic precursor cells to the liver. RESULTS: Treatment with G-CSF induced a twofold increase of peripheral white blood cells and a strong influx of granulopoietic precursor cells into the liver. Transplantation of a partial liver graft was followed by a 90% recovery of the original liver weight within a week, demonstrating the strong regenerative stimulus. Irrespective of the experimental model, the incidence and rate of Y-chromosome containing hepatocytes never exceeded 0.77%. CONCLUSION: Neither stem cell mobilization nor liver regeneration enhanced the incidence or rate of stem cell derived hepatocytes in a liver graft with unimpaired regenerative potential.
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OBJECTIVE: To explore the diagnosis, clinical manifestation, treatment, and prognosis of intraductal papillary mucinous neoplasms (IPMNs) of pancreas. METHODS: The clinical data of 38 patients with IPMNs, 23 males and 15 females, aged 64.1 +/- 10.7 (41 - 81), were analyzed respectively. RESULTS: The main symptoms included abdominal pain and jaundice. Pancreaticoduodenectomy was performed on 32 patients, total pancreatectomy on 1 patient, distal pancreatectomy on 3 patients; and pancreatic biopsy on 2 patients. One patient died during the peri-operational period. Pathology showed 15 cases of main-duct type, 14 cases of branch-duct type, 1 case of mixed type, and 8 cases being un-differentiated, all with dilatation of pancreatic duct at different degrees 4.6 mm in diameter on average. There were 30 cases of invasive IPMNs, with significantly higher level of carbohydrate antigen 19-9 (CA19-9), and 8 non-invasive. The median survival time was 18.5 months in general. In the invasive IPMN group the general median survival time was 16.1 months, and the 1, 2, and 5-year survival times were 54%, 31%, and 21% respectively; and in the non-invasive IPMN group the median survival time was 24.3 months, and the 1, 2, and 5-year survival times were 58% and 38% respectively; without significant differences in the survival times between these 2 groups. TMN staging showed 6 cases of stage 0, 15 cases of stage I, 9 cases of stage II, and 4 cases of stage III among the 34 patients of malignant IPMNs. The median survival times of the patients of the stages 0, I, II, and III were 31.3, 27, 9.1, and 8.9 months respectively with significant differences among them (P = 0.0124). CONCLUSION: IPMN of pancreas has no specific clinical manifestation. Dilatation of pancreatic duct is a manifestation in imaging examination characteristic of IPMN. The serum CA19-9 level is significantly higher in the patients with invasive IPMN. There are significant differences in survival rate among different groups according to TMN staging.
In vivo phage display is a technology used to reveal organ-specific vascular ligand-receptor systems in animal models and, recently, in patients, and to validate them as potential therapy targets. Here, we devised an efficient approach to simultaneously screen phage display libraries for peptides homing to any number of tissues without the need for an individual subject for each target tissue. We tested this approach in mice by selecting homing peptides for six different organs in a single screen and prioritizing them by using software compiled for statistical validation of peptide biodistribution specificity. We identified a number of motif-containing biological candidates for ligands binding to organ-selective receptors based on similarity of the selected peptide motifs to mouse proteins. To demonstrate that this methodology can lead to targetable ligand-receptor systems, we validated one of the pancreas-homing peptides as a mimic peptide of natural prolactin receptor ligands. This new comprehensive strategy for screening phage libraries in vivo provides an advantage over the conventional approach because multiple organs internally control for organ selectivity of each other in the successive rounds of selection. It may prove particularly relevant for patient studies, allowing efficient high-throughput selection of targeting ligands for multiple organs in a single screen.
A three-dimensional (3D) hyaluronic acid (HA) nanofibrous scaffold was successfully fabricated to mimic the architecture of natural extracellular matrix (ECM) based on electrospinning. Thiolated HA derivative, 3,3'-dithiobis(propanoic dihydrazide)-modified HA (HA-DTPH), was synthesized and electrospun to form 3D nanofibrous scaffolds. In order to facilitate the fiber formation during electrospinning, Poly (ethylene oxide) (PEO) was added into the aqueous solution of HA-DTPH at an optimal weight ratio of 1:1. The electrospun HA-DTPH/PEO blend scaffold was subsequently cross-linked through poly (ethylene glycol)-diacrylate (PEGDA) mediated conjugate addition. PEO was then extracted in DI water to obtain an electrospun HA-DTPH nanofibrous scaffold. NIH 3T3 fibroblasts were seeded on fibronectin-adsorbed HA-DTPH nanofibrous scaffolds for 24h in vitro. Fluorescence microscopy and laser scanning confocal microscopy revealed that the 3T3 fibroblasts attached to the scaffold and spread, demonstrating an extended dendritic morphology within the scaffold, which suggests potential applications of HA-DTPH nanofibrous scaffolds in cell encapsulation and tissue regeneration.
PURPOSE: Gemcitabine is a nucleoside analogue with activity against solid tumors. Gemcitabine metabolic inactivation is catalyzed by cytidine deaminase (CDA) or, after phosphorylation, by deoxycytidylate deaminase (DCTD). We set out to study the pharmacogenomics of CDA and DCTD. EXPERIMENTAL DESIGN: The genes encoding CDA and DCTD were resequenced using DNA from 60 African American and 60 Caucasian American subjects. Expression constructs were created for nonsynonymous coding single nucleotide polymorphisms (cSNP) and reporter gene constructs were created for 5'-flanking region polymorphisms. Functional genomic studies were then conducted after the transfection of mammalian cells. RESULTS: CDA resequencing revealed 17 polymorphisms, including one common nonsynonymous cSNP, 79 A>C (Lys27Gln). Recombinant Gln27 CDA had 66 +/- 5.1% (mean +/- SE) of the wild-type (WT) activity for gemcitabine but without a significant decrease in level of immunoreactive protein. The apparent Km (397 +/- 40 micromol/L) for the Gln27 allozyme was significantly higher than that for the WT (289 +/- 20 micromol/L; P < 0.025). CDA 5'-flanking region reporter gene studies showed significant differences among 5'-flanking region haplotypes in their ability to drive transcription. There were 29 SNPs in DCTD, including one nonsynonymous cSNP, 172 A>G (Asn58Asp), in Caucasian American DNA. Recombinant Asp58 DCTD had 11 +/- 1.4% of WT activity for gemcitabine monophosphate with a significantly elevated level of immunoreactive protein. No DCTD polymorphisms were observed in the initial 500 bp of the 5'-flanking region. CONCLUSIONS: These results suggest that pharmacogenomic variation in the deamination of gemcitabine and its monophosphate might contribute to variation in therapeutic response to this antineoplastic agent.
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Electrospinning has been emerging as one of the most efficient methods to fabricate polymer nanofibers. In this paper, PS/clay nanocomposite fibers with varying diameters were electrospun onto solid substrates. The fiber diameters were adjusted from 4 microm to 150 nm by changing the solution concentration. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM) were used to characterize the fiber morphology. Shear modulation force microscopy (SMFM) was utilized to investigate the surface nanomechanical properties of electrospun fibers as a function of the fiber diameter and temperature. In the absence of clay, no change in T(g) was observed, even though a large increase of shear modulus below the glass transition temperature was found. This effect was postulated to result from the molecular chain alignment during electrospinning. The addition of functionalized clays to the spinning solution produced fibers with a highly aligned montmorillonite layer structure at a clay concentration of 4 wt %. Clay agglomerates were observed at higher concentrations. The existence of clay further enhanced the shear modulus of fibers and increased the glass transition temperature by nearly 20 degrees C.
Produced by and purified from Taxus brevifolia, Taxol (paclitaxel) has become a widely used cancer drug in clinic. Due to the rapid growing market, current industrial production of taxol by semi-synthesis that consumes large amount of Taxus trees cannot meet the requirement of the market. The discovery of taxol-producing fungus Taxomyces andeanae, an endophyte of T. brevifolia, by Stierle et al (1993), paves a new way to the production of the drug, i.e. employing large-scale fungal fermentation to make Taxol at lower cost and yet higher yield. This review discusses the present problems in taxol production in pharmaceutical industry, the finding and research progress on taxol-producing fungi, and the potential application of fungal fermentation to manufacture this important drug.
OBJECTIVE: To clarify whether the various subtypes of serous cystic neoplasms (SCNs) of the pancreas can be distinguished from each other by marker profiles. METHODS: The immunoprofiles of 13 SCNs were defined by using antibodies against cytoskeletal, neuroendocrine, hormone receptor, and mucin markers. In addition, we examined the expression of calrentinin and alpha-inhibin. RESULTS: SCN included 7 cases of serous microcystic adenomas (SMA), 3 cases of serous oligocystic ill-defined adenomas (SOIA), 1 case of solid serous adenoma (SSA), 1 case of von Hippel-Lindau-associated cystic neoplasm (VHL-CN), and 1 case of serous cystadenocarcinoma (SCC). These neoplasms are histologically similar, but differ in their localization, gross appearance, gender distribution, and biological behavior. The various types of SCNs showed a very similar immunoprofile, characterized by positivity for cytokeratins (100%) and negativity for vimentin and synaptophysin. Other markers that were commonly expressed in the SCNs were alpha-inhibin (85%), MUC1 (69%) and MUC6 (77%). CONCLUSION: The results suggest that, despite their biologic differences, the various types of SCNs have the same (or a very similar) cell type and may therefore have a common direction of differentiation. A centroacinar origin is supported by the finding that a number of SCNs share MUC1 and MUC6 expression with pancreatic centroacinar cells. Alpha-inhibin, and MUC6 may be regarded as new markers for this type of pancreatic tumor.