Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used to treat chronic pain and inflammation. However, prolonged use of NSAIDs has been known to result in Gastrointestinal (GI) ulceration/bleeding, with a bile-mediated mechanism underlying their toxicity to the lower gut. Bile acids (BAs) and phosphatidylcholines (PCs), the major components of bile, form mixed micelles to reduce the membrane disruptive actions of monomeric BAs and simple BA micelles. NSAIDs are suspected to alter the BA/PC balance in the bile, but the molecular interactions of NSAID-BA or NSAID-BA-PC remain undetermined. In this work, we used a series of all-atom molecular dynamics simulations of cholic acid (CA), ibuprofen (IBU) and dodecylphosphocholine (DPC) mixtures to study the spontaneous aggregation of CA and IBU as well as their adsorption on a DPC micelle. We found that the size of CA-IBU mixed micelles varies with their molar ratio in a non-linear manner, and that micelles of different sizes adopt similar shapes but differ in composition and internal interactions. These observations are supported by NMR chemical shift changes, NMR ROESY crosspeaks between IBU and CA, and dynamic light scattering experiments. Smaller CA-IBU aggregates were formed in the presence of a DPC micelle due to the segregation of CA and IBU away from each other by the DPC micelle. While the larger CA-IBU aggregates arising from higher IBU concentrations might be responsible for NSAID-induced intestinal toxicity, the absence of larger CA-IBU aggregates in the presence of DPC micelles may explain the observed attenuation of NSAID toxicity by PCs.
Molecular dynamics; mixed micelle; cluster size; NSAID; bile acid
We propose a cross-correlation-based method to measure blood flow velocity by using photoacoustic microscopy. Unlike in previous auto-correlation-based methods, the measured flow velocity here is independent of particle size. Thus, an absolute flow velocity can be obtained without calibration. We first measured the flow velocity ex vivo, using defibrinated bovine blood. Then, flow velocities in vessels with different structures in a mouse ear were quantified in vivo. We further measured the flow variation in the same vessel and at a vessel bifurcation. All the experimental results indicate that our method can be used to accurately quantify blood velocity in vivo.
Epithelial growth factor (EGF) and basic fibroblast growth factor (bFGF), and their receptors, epithelial growth factor receptor (EGFR) and bFGF receptor (bFGFR), are frequently overexpressed in high-grade gliomas. In the present study, the EGF and bFGF levels in U251 glioblastoma cell culture supernatants were determined by ELISA, and enhanced green fluorescent protein (EGFP)-labeled recombinant lentiviral expression vectors with small interfering RNA targeting the EGFR and bFGFR genes were constructed. The mRNA expression levels of EGFR, bFGFR, cluster of differentiation (CD)133, glial fibrillary acidic protein (GFAP), tubulin-β3 (TUBB3) and myelin basic protein (MBP) were determined using quantitative polymerase chain reactions in U251 cells prior to and following silencing of the EGFR and/or bFGFR genes. Prior to silencing, the U251 cells secreted EGF and bFGF, and expressed EGFR, bFGFR, CD133, GFAP, TUBB3 and MBP mRNA. Subsequent to silencing the EGFR and/or bFGFR gene, CD133 mRNA expression decreased and GFAP and TUBB3 mRNA expression increased. Silencing the EGFR and FGFR genes acted synergistically to downregulate CD133 expression. The downregulation of CD133 mRNA expression and the upregulation of GFAP and TUBB3 mRNA expression were not significantly different when blocking the EGFR and FGFR pathways. These results indicate that autocrine or paracrine EGF and/or FGF mechanisms exist in U251 cells. Knocking down the EGFR and/or FGFR genes downregulates CD133 mRNA expression and facilitates glial and neuronal differentiation in U251 cells.
small interfering RNA; epidermal growth factor; bFGF; U251 glioblastoma cell; CD133; GFAP; TUBB4; MBP
To determine the optimal standardized uptake value (SUV) of 18F-fluorodeoxyglucose (18F-FDG) for positron emission tomography (PET) imaging, at which the PET-defined gross tumor volume (GTVPET) best matches with the pathological volume (GTVPATH) in the cervical cancer.
Materials and Methods
Ten patients with the cervical cancer who underwent surgery were enrolled in this study. The excised specimens were processed for whole-mount serial sections and H-E staining. The tumor borders were outlined in sections under a microscope, histopathological images were scanned and the GTVPATH calculated. The GTVPET was delineated automatically by using various percentages relative to the maximal SUV and absolute SUV. The optimal threshold SUV was further obtained as the value at which the GTVPET best matched with the GTVPATH.
An average of 85±10% shrinkage of tissue was observed after the formalin fixation. The GTVPATH was 13.38±2.80 cm3 on average. The optimal threshold on percentile SUV and absolute SUV were 40.50%±3.16% and 7.45±1.10, respectively. The correlation analysis showed that the optimal percentile SUV threshold was inversely correlated with GTVPATH (p<0.05) and tumor diameter (p<0.05). The absolute SUV was also positively correlated with SUVmax (p<0.05).
The pathological volume could provide the more accurate tumor volume. The optimal SUV of FDG for PET imaging by use of GTVPATH as standard for cervical cancer target volume delineation was thus determined in this study, and more cases are being evaluated to substantiate this conclusion.
AIM: To assess the theoretical advantages of magnetic endoscope imaging (MEI) over standard colonoscopies (SCs) and to compare their efficacies.
METHODS: Electronic databases, including PubMed, EMBASE, the Cochrane library and the Science Citation Index, were searched to retrieve relevant trials. In addition, abstracts from papers presented at professional meetings and the reference lists of retrieved articles were reviewed to identify additional studies. The meta-analyses were performed using RevMan 5.1. A random effect model with the Mantel-Haenszel method was used for pooling dichotomous and continuous data. A sensitivity analysis was performed by excluding the trials with a small number of patients and by excluding the trials performed by inexperienced providers.
RESULTS: Eight randomized controlled trials (RCTs), including 2967 patients, were included in the meta-analysis to compare cecal intubation rates and times, sedation dose, abdominal pain scores and the use of ancillary maneuvers between MEI and SC. The overall OR was 1.92 (95%CI: 1.13-3.27, eight RCTs), as indicated by the cecal intubation rate of MEI compared with SC, but MEI did not have any distinct advantage over SC for cecal intubation time (MD = -0.07, 95%CI: -0.16-0.02; three RCTs). MEI did not generally result in lower pain scores. Outcomes were also analyzed for the two subgroups based on the endoscopists’ experience level to evaluate cecal intubation rates. MEI presented better outcomes for non-experienced colonoscopists than experienced colonoscopists.
CONCLUSION: The real-time magnetic imaging system is of benefit in training and educating inexperienced endoscopists and improves the cecal intubation rate for experienced and inexperienced endoscopists.
Colonoscope; Magnetic endoscope imaging; Magnetic; Standard colonoscope; Meta-analysis
Valproic acid (VPA) is a well-tolerated drug that is used to treat seizure disorders and that has recently been shown to inhibit histone deacetylase. The present study investigated the effects of VPA on the radiosensitization of the rat C6 glioma cell line in vitro. To select an appropriate treatment concentration and time, MTT and flow cytometry assays were performed to measure the inhibitory effects of VPA at various concentrations and incubation time-points. The radiosensitizing effect of VPA was determined using clonogenic experiments. VPA- and radiation-induced C6 apoptosis was analyzed using quantitative polymerase chain reaction and western blot analysis. Cell proliferation was significantly inhibited by VPA in a time- and dose-dependent manner (P<0.05). VPA enhanced radiation-induced C6 cell death and there was clear inhibition of clonogenic formation [sensitizer enhancement ratio (SER), 1.30]. This effect was closely associated with the concentration of VPA. VPA treatment decreased the mRNA and protein levels of Bcl-2, whereas increased changes were detected with Bax. At a concentration of 0.5 mmol/l, VPA had a low toxicity and enhanced the radiosensitization of the C6 cells. VPA may radiosensitize glioma cells by inhibiting cellular proliferation and inducing apoptosis by regulating apoptosis-related molecular changes.
histone deacetylase inhibitors; valproic acid; gliomas; C6; radiosensitization; X-ray; apoptosis; in vitro
In cholestatic liver diseases, the ability of hydrophobic bile acids to damage membranes of hepatocytes/ductal cells contributes to their cytotoxicity. However, ursodeoxycholic acid (UDC), a hydrophilic bile acid, is used to treat cholestasis because it protects membranes. It has been well established that bile acids associate with and solubilize free cholesterol (CHOL) contained within the lumen of the gallbladder because of their structural similarities. However, there is a lack of understanding of how membrane CHOL, which is a well-established membrane stabilizing agent, is involved in cytotoxicity of hydrophobic bile acids and the cytoprotective effect of UDC. We utilized phospholipid liposomes to examine the ability of membrane CHOL to influence toxicity of individual bile acids, such as UDC and the highly toxic sodium deoxycholate (SDC), as well as the cytoprotective mechanism of UDC against SDC-induced cytotoxicity by measuring membrane permeation and intramembrane dipole potential. The kinetics of bile acid solubilization of phosphatidylcholine liposomes containing various levels of CHOL was also characterized. It was found that the presence of CHOL in membranes significantly reduced the ability of bile acids to damage synthetic membranes. UDC effectively prevented damaging effects of SDC on synthetic membranes only in the presence of membrane CHOL, while UDC enhances the damaging effects of SDC in the absence of CHOL. This further demonstrates that the cytoprotective effects of UDC depend upon the level of CHOL in the lipid membrane. Thus, changes in cell membrane composition, such as CHOL content, potentially influence the efficacy of UDC as the primary drug used to treat cholestasis.
Ursodeoxycholic acid cytoprotection; Deoxycholic acid cytotoxicity; Cholesterol; Membrane permeability; Membrane dipole potential; Turbidity
AIM: To investigate the mechanisms of how cyclooxygenase-2 (COX-2) regulates E-cadherin in gastric cancer cells.
METHODS: COX-2 expression in human gastric cancer cell lines SGC-7901, BGC-823, MGC-803 and AGS were measured at the mRNA and protein level. COX-2 rich cell line SGC-7901 was chosen for subsequent experiments. siRNA mediated gene knockdown was used to investigate the impact of COX-2 on nuclear factor-κB (NF-κB), Snail, and E-cadherin in gastric cancer cells. Gene expression was determined by Western blot and real-time polymerase chain reaction. To analyze whether NF-κB inhibition could interrupt the modulatory effect of COX-2 or prostaglandin E2 (PGE2) on E-cadherin, gastric cancer cells were treated with celecoxib or PGE2, in the presence of NF-κB specific siRNA.
RESULTS: Highest expression level of COX-2 was found in SGC-7901 cells, both at mRNA and protein levels. siRNA mediated down-regulation of COX-2 led to a reduced expression of NF-κB and Snail, but an increased expression of E-cadherin in SGC-7901 cells. siRNA mediated down-regulation of NF-κB also led to a reduced expression of E-cadherin and Snail in SGC-7901 cells. However, COX-2 expression did not alter after cells were treated with NF-κB specific siRNA in SGC-7901 cells. Treatment of SGC-7901 cells with celecoxib led to a reduced expression of Snail but an increased expression of E-cadherin. In contrast, treatment of SGC-7901 cells with PGE2 led to an increased Snail and a decreased E-cadherin. However, siRNA-mediated knockdown of NF-κB partially abolished the effect of celecoxib and PGE2 on the regulation of E-cadherin and Snail in SGC-7901 cells.
CONCLUSION: COX-2 likely functions upstream of NF-κB and regulates the expression of E-cadherin via NF-κB/Snail signaling pathway in gastric cancer cells.
Cyclooxygenase-2; E-cadherin; celecoxib; Prostaglandin E2; Gastric cancer
We developed random-access optical-resolution photoacoustic microscopy using a digital micromirror device. This system can rapidly scan arbitrarily shaped regions of interest within a 40×40 μm2 imaging area with a lateral resolution of 3.6 μm. To identify a region of interest, a global structural image is first acquired, then the selected region is scanned. The random-access ability was demonstrated by imaging two static samples, a carbon fiber cross and a monolayer of red blood cells, with an acquisition rate up to 4 kilohertz. The system was then used to monitor blood flow in vivo in real time within user-selected capillaries in a mouse ear. By imaging only the capillary of interest, the frame rate was increased by up to 9.2 times.
Pulmonary metastases are the major cause of death of osteosarcoma (OS) patients. Endothelin-1 (ET-1) reportedly plays an important role in OS metastasis. In the present study, we for the first time explored the association of ET-1 SNPs with the risk of pulmonary metastatic OS. We genotyped three SNPs (rs1800541, rs2070699 and rs5370) in the ET-1 gene in a case-control study, using 260 pairs of age-, sex-, residence area- and tumor location-matched subjects. Patients with pulmonary metastatic OS and patients with localized high-grade (stage IIB) OS were enrolled as cases and controls, respectively. The G allele at rs1800541 was found associated with reduced risk of pulmonary metastatic OS after adjustment for body mass index, systolic blood pressure, diastolic blood pressure and the plasma ET-1 level (P=10-4; adjusted OR, 0.55; 95% CI, 0.42-0.70), while the G allele at rs2070699 was not significantly associated with the risk of pulmonary metastatic OS (P=0.15; adjusted OR, 1.15; 95% CI, 0.87-1.50). The mRNA and the secreted protein levels of ET-1 in primary OS cell cultures (POCCs) established from surgically resected primary OS in the rs1800541 TT homozygotes were higher than those from the TG heterozygotes (P<0.05), who in turn showed higher ET-1 mRNA and secreted ET-1 levels than the GG homozygotes (P<0.05). In the control subjects, the rs1800541 TT homozygotes showed an 18.4% relapse rate, significantly higher than that of the GG homozygotes (0%) (P<0.01). On the other hand, the GG homozygotes showed a 71.4% complete recovery rate, significantly higher than that of the TG heterozygotes (7.3%) and the TT homozygotes (0%) (P<0.01). This study provides the first evidence of an association between the ET-1 gene SNPs and the risk of pulmonary metastatic OS.
As the final stage of leaf development, leaf senescence may cause the decline of photosynthesis and gradual reduction of carbon assimilation, which makes it a possible limiting factor for crop yield. NACs are plant-specific transcription factors and some NACs have been confirmed to play important roles in regulating leaf senescence.
In this study, we reported a member of the NAC transcription factor family named OsNAP whose expression is associated with leaf senescence, and investigated its preliminary function during the process of leaf senescence. The results of qRT-PCR showed that the OsNAP transcripts were accumulated gradually in response to leaf senescence and treatment with methyl jasmonic acid (MeJA). A subcellular localization assay indicated that OsNAP is a nuclear-localized protein. Yeast one-hybrid experiments indicated that OsNAP can bind the NAC recognition site (NACRS)-like sequence. OsNAP-overexpressing transgenic plants displayed an accelerated leaf senescence phenotype at the grain-filling stage, which might be caused by the elevated JA levels and the increased expression of the JA biosynthesis-related genes LOX2 and AOC1, and showed enhanced tolerance ability to MeJA treatment at the seedling stage. Nevertheless, the leaf senescence process was delayed in OsNAP RNAi transgenic plants with a dramatic drop in JA levels and with decreased expression levels of the JA biosynthesis-related genes AOS2, AOC1 and OPR7.
These results suggest that OsNAP acts as a positive regulator of leaf senescence and this regulation may occur via the JA pathway.
Chlorophyll; Leaf senescence; NAC; JA; Rice (Oryza sativa L.)
To prospectively explore the association between non-high-density lipoprotein cholesterol (non-HDLC) and the risks of stroke and its subtypes.
A total of 95,916 participants (18-98 years old; 76,354 men and 19,562 women) from a Chinese urban community who were free of myocardial infarction and stroke at baseline time point (2006-2007) were eligible and enrolled in the study. The serum non-HDLC levels of participants were determined by subtracting the high-density lipoprotein cholesterol (HDLC) from total serum cholesterol. The primary outcome was the first occurrence of stroke, which was diagnosed according to the World Health Organization criteria and classified into three subtypes: ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. The Cox proportional hazards models were used to estimate risk of stroke and its subtypes.
During the four-year follow-up, we identified 1614 stroke events (1,156 ischemic, 416 intracerebral hemorrhagic and 42 subarachnoid hemorrhagic). Statistical analyses showed that hazard ratios (HR) (95% Confidence Interval: CI) of serum Non-HDLC level for total and subtypes of stroke were: 1.08 (1.03-1.12) (total), 1.10 (1.05-1.16) (ischemic), 1.03 (0.96-1.10) (intracerebral hemorrhage) and 0.83 (0.66-1.05) (subarachnoid hemorrhage). HR for non-HDLC refers to the increase per each 20 mg/dl. For total and ischemic stroke, the risks were significantly higher in the fourth and fifth quintiles of non-HDLC concentrations compared to the first quintile after adjusting the confounding factors (total stroke: 4th quintile HR=1.33 (1.12-1.59); 5th quintile HR = 1.36 (1.15-1.62); ischemic stroke: 4th quintile HR =1.34 (1.09-1.66); 5th quintile HR = 1.53 (1.24-1.88)).
Our data suggest that serum non-HDLC level is an independent risk factor for total and ischemic stroke, and that higher serum non-HDLC concentrations are associated with increased risks for total stroke and ischemic stroke, but not for intracerebral and subarachnoid hemorrhage.
Chlorophylls (Chls) are crucial for capturing light energy for photosynthesis. Although several genes responsible for Chl biosynthesis were characterized in rice (Oryza sativa), the genetic properties of the hydrogenating enzyme involved in the final step of Chl synthesis remain unknown. In this study, we characterized a rice light-induced yellow leaf 1-1 (lyl1-1) mutant that is hypersensitive to high-light and defective in the Chl synthesis. Light-shading experiment suggested that the yellowing of lyl1-1 is light-induced. Map-based cloning of LYL1 revealed that it encodes a geranylgeranyl reductase. The mutation of LYL1 led to the majority of Chl molecules are conjugated with an unsaturated geranylgeraniol side chain. LYL1 is the firstly defined gene involved in the reduction step from Chl-geranylgeranylated (ChlGG) and geranylgeranyl pyrophosphate (GGPP) to Chl-phytol (ChlPhy) and phytyl pyrophosphate (PPP) in rice. LYL1 can be induced by light and suppressed by darkness which is consistent with its potential biological functions. Additionally, the lyl1-1 mutant suffered from severe photooxidative damage and displayed a drastic reduction in the levels of α-tocopherol and photosynthetic proteins. We concluded that LYL1 also plays an important role in response to high-light in rice.
The current gold standard for diagnosis of hepatic fibrosis and cirrhosis is the traditional invasive liver biopsy. It is desirable to assess hepatic fibrosis with noninvasive means. Targeted proteomic techniques allow an unbiased assessment of proteins and might be useful to identify proteins related to hepatic fibrosis. We utilized Selected Reaction Monitoring (SRM) targeted proteomics combined with an organ-specific blood protein strategy to identify and quantify 38 liver-specific proteins. A combination of protein C and retinol binding protein 4 in serum gave promising preliminary results as candidate biomarkers to distinguish patients at different stages of hepatic fibrosis due to chronic infection with hepatitis C virus (HCV). Also, alpha-1-B glycoprotein, complement factor H and insulin-like growth factor binding protein acid labile subunit performed well in distinguishing patients from healthy controls.
hepatitis C; fibrosis; liver-specific blood biomarkers; quantitation; selected reaction monitoring
Due to strong light scattering in tissue, both the spatial resolution and maximum penetration depth of optical-resolution photoacoustic microscopy (OR-PAM) deteriorate sharply with depth. To reduce tissue scattering, we propose to use glycerol as an optical clearing agent in OR-PAM. Our results show that the imaging performance of OR-PAM can be greatly enhanced by optical clearing both in vitro and in vivo.
The mechanical properties of the extracellular matrix have recently been shown to promote myofibroblast differentiation and lung fibrosis. Mechanisms by which matrix stiffness regulates myofibroblast differentiation are not fully understood. The goal of this study was to determine the intrinsic mechanisms of mechanotransduction in the regulation of matrix stiffness–induced myofibroblast differentiation. A well established polyacrylamide gel system with tunable substrate stiffness was used in this study. Megakaryoblastic leukemia factor-1 (MKL1) nuclear translocation was imaged by confocal immunofluorescent microscopy. The binding of MKL1 to the α-smooth muscle actin (α-SMA) gene promoter was quantified by quantitative chromatin immunoprecipitation assay. Normal human lung fibroblasts responded to matrix stiffening with changes in actin dynamics that favor filamentous actin polymerization. Actin polymerization resulted in nuclear translocation of MKL1, a serum response factor coactivator that plays a central role in regulating the expression of fibrotic genes, including α-SMA, a marker for myofibroblast differentiation. Mouse lung fibroblasts deficient in Mkl1 did not respond to matrix stiffening with increased α-SMA expression, whereas ectopic expression of human MKL1 cDNA restored the ability of Mkl1 null lung fibroblasts to express α-SMA. Furthermore, matrix stiffening promoted production and activation of the small GTPase RhoA, increased Rho kinase (ROCK) activity, and enhanced fibroblast contractility. Inhibition of RhoA/ROCK abrogated stiff matrix–induced actin cytoskeletal reorganization, MKL1 nuclear translocation, and myofibroblast differentiation. This study indicates that actin cytoskeletal remodeling–mediated activation of MKL1 transduces mechanical stimuli from the extracellular matrix to a fibrogenic program that promotes myofibroblast differentiation, suggesting an intrinsic mechanotransduction mechanism.
lung fibrosis; transcription factor; α-smooth muscle actin
The RON receptor tyrosine kinase, a member of the MET proto-oncogene family, is a pathogenic factor implicated in tumor malignancy. Specifically, aberrations in RON signaling result in increased cancer cell growth, survival, invasion, angiogenesis, and drug resistance. Biochemical events such as ligand binding, receptor overexpression, generation of structure-defected variants, and point mutations in the kinase domain contribute to RON signaling activation. Recently, functional crosstalk between RON and signaling proteins such as MET and EFGR has emerged as an additional mechanism for RON activation, which is critical for tumorigenic development. The RON signaling crosstalk acts either as a regulatory feedback loop that strengthens or enhances tumorigenic phenotype of cancer cells or serves as a signaling compensatory pathway providing a growth/survival advantage for cancer cells to escape targeted therapy. Moreover, viral oncoproteins derived from Friend leukemia or Epstein-Barr viruses interact with RON to drive viral oncogenesis. In cancer cells, RON signaling is integrated into cellular signaling network essential for cancer cell growth and survival. These activities provide the molecular basis of targeting RON for cancer treatment. In this review, we will discuss recent data that uncover the mechanisms of RON activation in cancer cells, review evidence of RON signaling crosstalk relevant to cancer malignancy, and emphasize the significance of the RON signaling addiction by cancer cells for tumor therapy. Understanding aberrant RON signaling will not only provide insight into the mechanisms of tumor pathogenesis, but also lead to the development of novel strategies for molecularly targeted cancer treatment.
Receptor tyrosine kinase (RON); signaling pathway; activation mechanism; signaling crosstalk; oncogene addiction; tumorigenesis
Aims. This study evaluated feasibility and safety of implanting the polyester-coated nitinol ventricular septal defect occluder (pcVSDO) in the canine model. Methods and Results. VSD models were successfully established by transseptal ventricular septal puncture via the right jugular vein in 15 out of 18 canines. Two types of VSDOs were implanted, either with pcVSDOs (n = 8) as the new type occluder group or with the commercial ventricular septal defect occluders (VSDOs, n = 7, Shanghai Sharp Memory Alloy Co. Ltd.) as the control group. Sheath size was 10 French (10 Fr) in two groups. Then the general state of the canines was observed after implantation. ECG and TTE were performed, respectively, at 7, 30, 90 days of follow-up. The canines were sacrificed at these time points for pathological and scanning electron microscopy examination. The devices were successfully implanted in all 15 canines and were retrievable and repositionable. There was no thrombus formation on the device or occurrence of complete heart block. The pcVSDO surface implanted at day 7 was already covered with neotissue by gross examination, and it completed endothelialization at day 30, while the commercial VSDO was covered with the neotissue in 30th day and the complete endothelialization in 90th day. Conclusion. The study shows that pcVSDO is feasible and safe to close canine VSD model and has good biocompatibility and shorter time of endothelialization.
Current tendon repair techniques do not provide sufficient tensile strength at the repair site, and thus early active motion rehabilitation after tendon repair is discouraged. To enhance the post-operative tensile strength, we proposed and tested an internal fixation technique using a polycaprolactone (PCL) biofilm. PCL was chosen for its good biocompatibility, excellent mechanical strength, and an appropriate degradation time scale.
PCL biofilms were prepared by a modified melt-molding/leaching technique, and the physical and mechanical properties and in vitro degradation rate were assessed. The pore size distribution of the biofilm and the paratenon of native tendons were observed using scanning electron microscopy. Next, we determined whether this biofilm could enhance the tensile strength of repaired tendons. We performed tensile tests on rabbit Achilles tendons that were first lacerated and then repaired: 1) using modified Kessler suture combined with running peripheral suture (‘control’ group), or 2) using biofilm to wrap the tendon and then fixation with sutures (‘biofilm’ group). The influence of different repair techniques on tendon tensile strength was evaluated by mechanical testing.
The novel biofilm had supple texture and a smooth surface. The mean thickness of the biofilm was 0.25 mm. The mean porosity of the biofilm was 45.3%. The paratenon of the rabbit Achilles tendon had pores with diameters ranging from 1 to 9 μm, which were similar to the 4–12 μm diameter pores in the biofilm cross-section. The weight loss of the biofilms at 4 weeks was only 0.07%. The molecular weight of PCL biofilms did not change after immersion in phosphate buffered saline for 4 weeks. The failure loads of the biofilm were similar before (48 ± 9 N) and after immersion (47 ± 7 N, P > 0.1). The biofilm group had ~70% higher mean failure loads and 93% higher stiffness compared with the control group.
We proposed and tested an internal fixation technique using a PCL biofilm to enhance tendon repair. Internal fixation with the biofilm followed by standard suturing can significantly increase the tensile strength of tendon repair sites. This technique has the potential to allow active motion rehabilitation during the early post-operative period.
Tendon injury; Internal fixation; Biomechanics; Microstructure
Single- and low-copy genes are less likely to be subject to concerted evolution. Thus, they are appropriate tools to study the origin and evolution of polyploidy plant taxa. The plastid 3-phosphoglycerate kinase gene (Pgk-1) sequences from 44 accessions of Triticum and Aegilops, representing diploid, tetraploid, and hexaploid wheats, were used to estimate the origin of Triticum petropavlovskyi. Our phylogenetic analysis was carried out on exon+intron, exon and intron sequences, using maximum likelihood, Bayesian inference and haplotype networking. We found the D genome sequences of Pgk-1 genes from T. petropavlovskyi are similar to the D genome orthologs in T. aestivum, while their relationship with Ae. tauschii is more distant. The A genome sequences of T. petropavlovskyi group with those of T. polonicum, but its Pgk-1 B genome sequences to some extent diverge from those of other species of Triticum. Our data do not support for the origin of T. petropavlovskyi either as an independent allopolyploidization event between Ae. tauschii and T. polonicum, or as a monomendelian mutation in T. aestivum. We suggest that T. petropavlovskyi originated via spontaneous introgression from T. polonicum into T. aestivum. The dating of this introgression indicates an age of 0.78 million years; a further mutation event concerning the B genome occurred 0.69 million years ago.
TGF-β, a mediator of pulmonary fibrosis, is a genetic modifier of CF respiratory deterioration. The mechanistic relationship between TGF-β signaling and CF lung disease has not been determined.
To investigate myofibroblast differentiation in CF lung tissue as a novel pathway by which TGF-β signaling may contribute to pulmonary decline, airway remodeling and tissue fibrosis.
Lung samples from CF and non-CF subjects were analyzed morphometrically for total TGF-β1, TGF-β signaling (Smad2 phosphorylation), myofibroblast differentiation (α-smooth muscle actin), and collagen deposition (Masson trichrome stain).
TGF-β signaling and fibrosis are markedly increased in CF (p<0.01), and the presence of myofibroblasts is four-fold higher in CF vs. normal lung tissue (p<0.005). In lung tissue with prominent TGF-β signaling, both myofibroblast differentiation and tissue fibrosis are significantly augmented (p<0.005).
These studies establish for the first time that a pathogenic mechanism described previously in pulmonary fibrosis is also prominent in cystic fibrosis lung disease. The presence of TGF-β dependent signaling in areas of prominent myofibroblast proliferation and fibrosis in CF suggests that strategies under development for other pro-fibrotic lung conditions may also be evaluated for use in CF.
Background and purpose
Early and accurate diagnosis of stroke by emergency medical service (EMS) paramedics is critical for reducing pre-hospital delays. The Los Angeles pre-hospital stroke screen (LAPSS) has been widely used as a validated screening tool for early identifying stroke patients by EMS paramedics. However, validation of LAPSS has never been performed in Chinese stroke population. This study is aimed to verify the LAPSS for early identifying stroke patients in a Chinese urban EMS.
76 paramedics of five urban first aid stations attached to Beijing 120 EMS were involved. The paramedics were trained by professionals to quickly screen patients based on LAPSS. Potential “target stroke” individuals who met the base LAPSS screen criteria were identified. Sensitivity and specificity analyses of the LAPSS were calculated.
From June 10, 2009 to June 10, 2010, paramedics transported a total of 50,220 patients. 1550 patients who met the baseline screen criteria were identified as the potential “target stroke” population. 1130 patients had the completed LAPSS information datasheet and 997 patients were clinically diagnosed with stroke. The average time of completing the LAPSS was 4.3±3.0 minutes (median, 5 minutes). The sensitivity and specificity of the LAPSS in this study was 78.44% and 90.22%, respectively. After adjusting for age factor by excluding patients of >45 years old, the sensitivity was significantly increased to 82.95% with specificity unchanged.
The paramedics of Beijing 120 EMS could efficiently use LAPSS as a screening tool for early identifying stroke patients. While the sensitivity of LAPSS in Chinese urban patient population was lower than those reported in previous LAPSS validation studies, the specificity was consistent with these studies. After excluded the item of “Age>45 years”, the sensitivity was improved.
We report a method to promote photoluminescence emission in graphene materials by enhancing carrier scattering instead of directly modifying band structure in multilayer reduced graphene oxide (rGO) nanospheres. We intentionally curl graphene layers to form nanospheres by reducing graphene oxide with spherical polymer templates to manipulate the carrier scattering. These nanospheres produce hot-carrier luminescence with more than ten-fold improvement of emission efficiency as compared to planar nanosheets. With increasing excitation power, hot-carrier luminescence from nanospheres exhibits abnormal spectral redshift with dynamic feature associated to the strengthened electron-phonon coupling. These experimental results can be well understood by considering the screened Coulomb interactions. With increasing carrier density, the reduced screening effect promotes carrier scattering which enhances hot-carrier emission from such multilayer rGO nanospheres. This carrier-scattering scenario is further confirmed by pump-probe measurements.