LncRNAs have become rising stars in biology and medicine, due to their versatile functions in a wide range of important biological processes and active roles in various human cancers. Here, we developed a computational method based on the naïve Bayesian classifier method to identify cancer-related lncRNAs by integrating genome, regulome and transcriptome data, and identified 707 potential cancer-related lncRNAs. We demonstrated the performance of the method by ten-fold cross-validation, and found that integration of multi-omic data was necessary to identify cancer-related lncRNAs. We identified 707 potential cancer-related lncRNAs and our results showed that these lncRNAs tend to exhibit significant differential expression and differential DNA methylation in multiple cancer types, and prognosis effects in prostate cancer. We also found that these lncRNAs were more likely to be direct targets of TP53 family members than others. Moreover, based on 147 lncRNA knockdown data in mice, we validated that four of six mouse orthologous lncRNAs were significantly involved in many cancer-related processes, such as cell differentiation and the Wnt signaling pathway. Notably, one lncRNA, lnc-SNURF-1, which was found to be associated with TNF-mediated signaling pathways, was up-regulated in prostate cancer and the protein-coding genes affected by knockdown of the lncRNA were also significantly aberrant in prostate cancer patients, suggesting its probable importance in tumorigenesis. Taken together, our method underlines the power of integrating multi-omic data to uncover cancer-related lncRNAs.
The promise of cell therapy for repair and restoration of damaged tissues or organs relies on administration of large dose of cells whose healing benefits are still limited and sometimes irreproducible due to uncontrollable cell loss and death at lesion sites. Using a large amount of therapeutic cells increases the costs for cell processing and the risks of side effects. Optimal cell delivery strategies are therefore in urgent need to enhance the specificity, efficacy, and reproducibility of cell therapy leading to minimized cell dosage and side effects. Here, we addressed this unmet need by developing injectable 3D microscale cellular niches (microniches) based on biodegradable gelatin microcryogels (GMs). The microniches are constituted by in vitro priming human adipose-derived mesenchymal stem cells (hMSCs) seeded within GMs resulting in tissue-like ensembles with enriched extracellular matrices and enhanced cell-cell interactions. The primed 3D microniches facilitated cell protection from mechanical insults during injection and in vivo cell retention, survival, and ultimate therapeutic functions in treatment of critical limb ischemia (CLI) in mouse models compared with free cell-based therapy. In particular, 3D microniche-based therapy with 10(5) hMSCs realized better ischemic limb salvage than treatment with 10(6) free-injected hMSCs, the minimum dosage with therapeutic effects for treating CLI in literature. To the best of our knowledge, this is the first convincing demonstration of injectable and primed cell delivery strategy realizing superior therapeutic efficacy for treating CLI with the lowest cell dosage in mouse models. This study offers a widely applicable cell delivery platform technology to boost the healing power of cell regenerative therapy.
In order to obtain precise reconstruction results in fluorescence molecular tomography (FMT), large-scale matrix equations would be solved in the inverse problem generally. Thus, much time and memory needs to be consumed. In this paper, a permissible region extraction strategy is proposed to solve this problem. First, a preliminary result is rapidly reconstructed using the weight matrix compressed by principal component analysis or uniform sampling. And then the reconstructed target area in this preliminary result is considered as the a priori permissible region to guide the final reconstruction. Phantom experiments with double fluorescent targets are performed to test the performance of the strategy. The results illustrate that the proposed strategy can significantly accelerate the image reconstruction in FMT almost without quality degradation.
Research on the migration and transformation of phenol with space and temporal variability in the vadose zone is hindered by monitoring technology in field experiments. Four column experiments were conducted to investigate the effect of porous media size, volatilization, biological effects, and oxidation on the transport of phenol in the vadose zone. The initial inflow phenol concentration of each column was 500 mg/L, and the final outflow concentrations were 0, 348, 240, and 365 mg/L, More than 90% of reduction of phenol concentration occurred at the top of the simulation column. Results show that volatilization and oxidation are the main factors that could lead to the decrease of phenol concentration in an open system. However, these two processes cannot be accurately separated. The migration rate of phenol was larger in coarse sands (6.06 cm/d) than in fine sands (4.55 cm/d). Phenol biodegradation did not occur under experimental conditions. However, mercury (as biological inhibitor) could react with phenol to generate a mercury-phenol complex, which could lead to the reduction of phenol concentration to 21.6% in the simulation experiment.
It is a challenging problem to resolve and identify drug (or non-specific fluorophore) distribution throughout the whole body of small animals in vivo. In this article, an algorithm of unmixing multispectral fluorescence tomography (MFT) images based on independent component analysis (ICA) is proposed to solve this problem. ICA is used to unmix the data matrix assembled by the reconstruction results from MFT. Then the independent components (ICs) that represent spatial structures and the corresponding spectrum courses (SCs) which are associated with spectral variations can be obtained. By combining the ICs with SCs, the recovered MFT images can be generated and fluorophore concentration can be calculated. Simulation studies, phantom experiments and animal experiments with different concentration contrasts and spectrum combinations are performed to test the performance of the proposed algorithm. Results demonstrate that the proposed algorithm can not only provide the spatial information of fluorophores, but also recover the actual reconstruction of MFT images.
A simple, rapid and environmental friendly online chemical oxygen demand (COD) analytical method based on TiO2 nanotube sensor in conjunction with the flow injection technique was proposed to determine the COD of aqueous samples, especially for refractory organics, low-concentration wastewater, and surface water. The new method can overcome the drawbacks of the conventional COD determination methods. The results show that with the new method, each analysis takes only about 1 to 3 min, the linear range is up to 1 to 500 mg x L(-1) of the compound of interest, and the detection limit is 1 mg x L(-1). The COD values obtained by the proposed method are more accurate than those obtained by the conventional method.
A study of the interactions between nanoparticles and living cells is invaluable in understanding the nano-biological effect and the mechanism of cellular endocytosis. Here we describe two methods for the preparation of semiconductor quantum dots with different physiochemical properties. Furthermore, we describe how to study the interaction of the two quantum dots with living HeLa cells and red blood cells with confocal microscopy.
In ultrasound elastography, reconstruction of tissue elasticity (e.g., Young's modulus) requires regularization and known information of forces and/or displacements on tissue boundaries. In practice, it is challenging to choose an appropriate regularization parameter; and the boundary conditions are difficult to obtain in vivo. The purpose of this study is to develop a more applicable algorithm that does not need any regularization or boundary force/displacement information.
Dynamic fluorescence molecular tomography (DFMT) is a potential approach for drug delivery, tumor detection, diagnosis and staging. The purpose of DFMT is to quantify the changes of fluorescent agents in the bodies, which offer important information about the underlying physiological processes. However, the conventional method requires that the fluorophore concentrations to be reconstructed are stationary during the data collection period. As thus, it cannot offer the dynamic information of fluorophore concentration variation within the data collection period. In this paper, a method is proposed to reconstruct the fluorophore concentration variation instead of the fluorophore concentration through a linear approximation. The fluorophore concentration variation rate is introduced by the linear approximation as a new unknown term to be reconstructed and is used to obtain the time courses of fluorophore concentration. Simulation and phantom studies are performed to validate the proposed method. The results show that the method is able to reconstruct the fluorophore concentration variation rates and the time courses of fluorophore concentration with relative errors less than 0.0218.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by significant goblet hyperplasia and mucus hypersecretion. However, the molecular mechanism underlying mucin overexpression in CRSwNP has not been well characterized. This study sought to assess the expression of SAM-pointed domain-containing Ets-like factor (SPDEF) and its regulation of mucin production in CRSwNP patients.
Our aim was to identify the role of the homeostatic chemokines CCL19 and CCL21 and their common receptor CCR7 in atherogenesis and to study the relationships between CCL19, CCL21, and CCR7 gene variants and coronary artery disease in a Chinese Han population.
Transitions in community genomic features and biogeochemical processes were examined in surface and subsurface chlorophyll maximum (SCM) microbial communities across a trophic gradient from mesotrophic waters near San Diego, California to the oligotrophic Pacific. Transect end points contrasted in thermocline depth, rates of nitrogen and CO2 uptake, new production and SCM light intensity. Relative to surface waters, bacterial SCM communities displayed greater genetic diversity and enrichment in putative sulfur oxidizers, multiple actinomycetes, low-light-adapted Prochlorococcus and cell-associated viruses. Metagenomic coverage was not correlated with transcriptional activity for several key taxa within Bacteria. Low-light-adapted Prochlorococcus, Synechococcus, and low abundance gamma-proteobacteria enriched in the>3.0-?m size fraction contributed disproportionally to global transcription. The abundance of these groups also correlated with community functions, such as primary production or nitrate uptake. In contrast, many of the most abundant bacterioplankton, including SAR11, SAR86, SAR112 and high-light-adapted Prochlorococcus, exhibited low levels of transcriptional activity and were uncorrelated with rate processes. Eukaryotes such as Haptophytes and non-photosynthetic Aveolates were prevalent in surface samples while Mamielles and Pelagophytes dominated the SCM. Metatranscriptomes generated with ribosomal RNA-depleted mRNA (total mRNA) coupled to in vitro polyadenylation compared with polyA-enriched mRNA revealed a trade-off in detection eukaryotic organelle and eukaryotic nuclear origin transcripts, respectively. Gene expression profiles of SCM eukaryote populations, highly similar in sequence identity to the model pelagophyte Pelagomonas sp. CCMP1756, suggest that pelagophytes are responsible for a majority of nitrate assimilation within the SCM.
Peptides from scorpion venom have been previously studied for use in the prevention and treatment of various types of cancer in folk medicine. The present study investigated the anti-proliferative effects and mechanisms of the low molecular weight (~3 kDa) BmK scorpion venom peptides (LMWSVP) on human hepatoma (SMMC 7721) and cervical carcinoma (HeLa) cells. The data indicated that LMWSVP inhibited the growth of SMMC 7721 cells, but had no effect on the growth of HeLa cells. SMMC 7721 cells were more sensitive, with a higher affinity, to LMWSVP as compared with HeLa cells. In addition, LMWSVP induced apoptosis of SMMC 7721 cells by upregulating the expression of caspase-3 and downregulating the expression of Bcl-2. These data provide an experimental basis for further purification and application of LMWSVP for use as an anti-tumor drug in clinical trials.
Inflammatory bowel disease (IBD), which can increase the risk of colorectal cancer (CRC), includes two primary subtypes, ulcerative colitis (UC) and Crohn's disease (CD). Although several individual genes involved in inflammation or cancer characterization have been identified, it is still difficult to elucidate functional relationship details between the molecules underlying pathogenesis at the system level. The global effect of miRNAs on genes or their involved functions is also poorly understood. We first integrated genome-wide gene expression profiles and biological pathway information to explore the underlying associations among UC, CD and CRC at the function and gene level. After identifying the pathways regulated by miRNAs, a global map of miRNA-mediated pathway crosstalk shared by the three diseases was further constructed to vertically explain the links of three level alterations. The three types of diseases have close associations with each other at the levels of function, gene and miRNA regulation. Several key biological pathways are involved in the three diseases, related to the immune system and inflammation, metabolism, or cell proliferation and apoptosis etc. Moreover, miRNAs exhibit dominant effects on multiple pathways. It is worth noting that UC shows relatively close associations with CD and CRC at the three levels. Finally, the miRNAs could mediate the crosstalk within or between pathways. For example, hsa-miR-125b, hsa-miR-335 and hsa-miR-155 mediated the crosstalk between three metabolic pathways. The crosstalk within the Toll-like receptor signaling pathway could be mediated by hsa-miR-124, hsa-miR-146a and hsa-mir-221/222. Our results make sense for the prevention and treatment of intestinal-related chronic inflammation or cancer.
SNAIL and SLUG are zinc-finger transcription factors that participate in the regulation of cell division, cell survival, mesoderm formation and epithelial-to-mesenchymal transition. We investigate the expression of SNAIL and SLUG during follicular maturation, ovulation and luteinization in the ovaries of both neonatal mice and gonadotropin-induced immature mice. Furthermore, we examine the expression and localization of these transcription factors during early embryonic cleavage. Our data demonstrate that both SNAIL and SLUG are present in the epithelial cells of the ovarian surface in immature mice. SNAIL is first evident in the interstitial cells and theca cells by postnatal day (PD) 6 and then appears in the oocytes by PD 8, remaining at a constant expression level for all stages studied thereafter. SLUG is expressed in oocytes as early as PD 1. Its expression also increases with the development of the follicles in theca and interstitial cells but not in granulosa cells. In gonadotropin-induced immature mice, both SNAIL and SLUG are expressed in the corpora lutea. During early embryo cleavage, SNAIL occurs in the nucleus and cytoplasm of the majority of the embryo, excluding the nucleolus from the germinal vesicle breakdown (GVBD) to the 8-cell stage and is then localized in the cytoplasm during the morula stage and in the nucleus during the blastocyst stage. SLUG has an identical expression pattern as SNAIL from GVBD until the morula stage, except that it is localized in the cytoplasm during the blastocyst stage. Taken together, these different localization patterns suggest that SNAIL and SLUG probably play important roles during follicular development, luteinization and early embryonic development.
Corticosteroids have been shown to improve the outcome of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, whether inhaled corticosteroids (IC) alone have similar effects with systemic corticosteroid (SCS) is still unclear.
A sensor of a WO3 nanopores electrode combined with a thin layer reactor was proposed to develop a Chemical Oxygen Demand (COD) determination method and solve the problem that the COD values are inaccurately determined by the standard method. The visible spectrum, e.g., 420 nm, could be used as light source in the sensor we developed, which represents a breakthrough by limiting of UV light source in the photoelectrocatalysis process. The operation conditions were optimized in this work, and the results showed that taking NaNO3 solution at the concentration of 2.5 mol·L(-1) as electrolyte under the light intensity of 214 ?W·cm(-2) and applied bias of 2.5 V, the proposed method is accurate and well reproducible, even in a wide range of pH values. Furthermore, the COD values obtained by the WO3 sensor were fitted well with the theoretical COD value in the range of 3-60 mg·L(-1) with a limit value of 1 mg·L(-1), which reveals that the proposed sensor may be a practical device for monitoring and controlling surface water quality as well as slightly polluted water.
The purpose of the present study was to clarify the association of eNOS 894G/T and ACE I/D genetic polymorphisms with the risk of coronary heart disease (CHD) and to explore the effects of these polymorphisms on the therapeutic efficacy of salvianolate injection in Chinese CHD patients. In all, 153 CHD patients and 198 healthy controls were enrolled in the study. We collected 5 mL peripheral blood for DNA extraction. Genetic diagnosis of eNOS 894G/T was determined by direct sequencing. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to detect ACE I/D genotypes. We observed significant differences in the frequency distribution of eNOS and ACE polymorphisms between CHD patients and healthy controls (P < 0.05). Binary logistic regression stepwise analysis revealed that the genotypes had an additive and dominant effect on patients' therapeutic responses (P < 0.05). These data suggest that the genetic polymorphisms of ACE I/D and eNOS 894G/T probably play a role in the development of CHD and these genetic polymorphisms may affect the response to salvianolate injection in Chinese CHD patients.
The ozonolysis of 2,3,7,8-tetra-chlorodibenzo-p-dioxin (2,3,7,8-TCDD) is an efficient degradation way in the atmosphere. The ozonolysis process and possible reactions path of Criegee Intermediates with NO and H2O are introduced in detail at the method of MPWB1K/6-31+G(d,p)//MPWB1K/6-311+G(3df,2p) level. In ozonolysis, H2O is an important source of OH radical formation and initiated the subsequent degradation reaction. The Rice-Ramsperger-Kassel-Marcus (RRKM) theory was applied to calculate rate constants with the temperature ranging from 200 to 600 K. The rate constant of reaction between 2,3,7,8-TCDD and O3 is 4.80 x 10(-20) cm3/(mole x sec) at 298 K and 760 Torr. The atmospheric lifetime of the reaction species was estimated according to rate constants, which is helpful for the atmospheric model study on the degradation and risk assessment of dioxin.
Penicillium marneffei is a thermally dimorphic pathogenic fungus that causes systemic infection similar to disseminated cryptococcosis. P. marneffei is endemic in Southeast Asia, usually infecting HIV-infected individuals; infection of HIV-negative individuals is extremely rare. Here, we describe a disseminated P. marneffei infection within an osteolytic lesion in an HIV-negative patient. A 40-year-old Chinese woman presented with intermittent fever, generalized lymphadenopathy, and a skin rash. Following a sternum biopsy, the patient was diagnosed with P. marneffei infection. An emission computed tomography bone scan revealed the presence of increased radioactivity in the left clavicle and sternum, indicative of an osteolytic lesion. In addition to reporting this very rare case, we also present a brief review of the literature, highlighting the differences in clinical manifestations between HIV-positive and HIV-negative patients infected with P. marneffei as it applies to our case.
Owing to the high degree of scattering of light through tissues, the ill-posedness of fluorescence molecular tomography (FMT) inverse problem causes relatively low spatial resolution in the reconstruction results. Unlike L2 regularization, L1 regularization can preserve the details and reduce the noise effectively. Reconstruction is obtained through a restarted L1 regularization-based nonlinear conjugate gradient (re-L1-NCG) algorithm, which has been proven to be able to increase the computational speed with low memory consumption. The algorithm consists of inner and outer iterations. In the inner iteration, L1-NCG is used to obtain the L1-regularized results. In the outer iteration, the restarted strategy is used to increase the convergence speed of L1-NCG. To demonstrate the performance of re-L1-NCG in terms of spatial resolution, simulation and physical phantom studies with fluorescent targets located with different edge-to-edge distances were carried out. The reconstruction results show that the re-L1-NCG algorithm has the ability to resolve targets with an edge-to-edge distance of 0.1 cm at a depth of 1.5 cm, which is a significant improvement for FMT.
Forsythin (FOR) is an active ingredient extracted from the fruit of the medicinal plant Forsythia suspensa (Thunb.) Vahl. Here, we investigated the effect of FOR on LPS-induced inflammatory response and the underlying molecular mechanisms in RAW264.7 macrophages.
The synergistic therapy, the combination of photothermal therapy and chemotherapy, has become a potential treatment in the battles with cancer. Here, we developed a synergistic therapy tool that based on CuS nanoparticles-decorated graphene oxide functionalized with polyethylene glycol (PEG-GO/CuS) for cervical cancer treatment. The as-synthesized PEG-GO/CuS nanocomposites with excellent biocompatibility was revealed to have high storage capacity for anticancer drug of doxorubicin (Dox) and high photothermal conversion efficiency, and were effectively employed for the ablation of tumor. In addition, the therapeutic efficacy of Dox-loaded PEG-GO/CuS (PEG-GO/CuS/Dox) nanocomposites was evaluated in vitro and in vivo for cervical cancer therapy. In vitro cell cytotoxicity tests of PEG-GO/CuS/Dox demonstrate about 1.3 and 2.7-fold toxicity than PEG-GO/CuS and free Dox under 5 min irradiation with NIR laser at 1.0 W/cm(2), owing to both PEG-GO/CuS-mediated photothermal ablation and cytotoxicity of light-triggered Dox release. In mouse models, mouse cervical tumor growth was found to be significantly inhibited by the chemo-photothermal effect of PEG-GO/CuS/Dox nanocomposites, resulting in effective tumor reduction. Overall, compared with chemotherapy or photothermal therapy alone, the combined treatment demonstrates better therapeutic efficacy of cancer in vitro and in vivo. These findings highlight the promise of the highly versatile multifunctional nanoparticles in biomedical application.
In conventional fluorescence molecular tomography, the distribution of fluorescent contrast agents is reconstructed with the assumption of constant concentration during data acquisition for each image frame. However, the concentration of fluorescent contrast target is usually time-varying in experiments or in-vivo studies. In this case, the reconstruction methods cannot be directly applied to the fluorescence measurements without considering the time-varying effects of concentration. We propose a modified forward model by dividing the fluorescence yield distribution into two parts: one is a constant representing the spatial distribution of the fluorescent target and the other is an impact factor representing the effects of the concentration change and other possible factors. By extracting spatial distribution information from the reconstruction result, the location and volume of the fluorescent target can be obtained accurately. Both simulation and phantom experiments are carried out and the results indicate that, by using the modified forward model, the quality of reconstruction could be significantly improved in terms of accurate localization and strong anti-noise ability.
The aim of this study was to investigate the effects of mental resilience on the changes of serum rennin, angiotensin, and cortisol level induced by sleep deprivation in servicemen. By random cluster sampling, a total of 160 servicemen, aged from 18 to 30, were selected to undergo 24-hour total sleep deprivation and administered the military personnel mental resilience scale after the deprivation procedure. The sleep deprivation procedure started at 8 a.m. on Day 8 and ended at 8 a.m. on Day 9 after 7 days of normal sleep for baseline preparation. Blood samples were drawn from the 160 participants at 8 a.m. respectively on Day 8 and Day 9 for hormonal measurements. All blood samples were analyzed using radioimmunoassay. As hypothesized, serum rennin, angiotensin II, and cortisol level of the participants after sleep deprivation were significantly higher than those before (P < 0.05). The changes of serum rennin and cortisol in the lower mental resilience subgroup were significantly greater (P < 0.05); problem-solving skill and willpower were the leading influence factors for the increases of serum rennin and cortisol respectively induced by sleep deprivation. We conclude that mental resilience plays a significant role in alleviating the changes of neurohormones level induced by sleep deprivation in servicemen.
Development of new, antimetastatic drugs from natural products has been substantially constrained by the lack of a reliable in vitro screening system. Such a system should ideally mimic the native, three-dimensional (3D) tumor microenvironment involving different cell types and allow quantitative analysis of cell behavior critical for metastasis. These requirements are largely unmet in the current model systems, leading to poor predictability of the in vitro collected data for in vivo trials, as well as prevailing inconsistency among different in vitro tests. In the present study, we report application of a 3D, microfluidic device for validation of the antimetastatic effects of 12 natural compounds. This system supports co-culture of endothelial and cancer cells in their native 3D morphology as in the tumor microenvironment and provides real-time monitoring of the cells treated with each compound. We found that three compounds, namely sanguinarine, nitidine, and resveratrol, exhibited significant antimetastatic or antiangiogenic effects. Each compound was further examined for its respective activity with separate conventional biological assays, and the outcomes were in agreement with the findings collected from the microfluidic system. In summary, we recommend use of this biomimetic model system as a new engineering tool for high-throughput evaluation of more diverse natural compounds with varying anticancer potentials.
Images of pharmacokinetic parameters in dynamic fluorescence molecular tomography (FMT) have the potential to provide quantitative physiological information for biological studies and drug development. However, images obtained with conventional indirect methods suffer from low signal-to-noise ratio because of failure in efficiently modeling the measurement noise. Besides, FMT suffers from low spatial resolution due to its ill-posed nature, which further reduces the image quality. In this letter, we present a direct method with structural priors for imaging pharmacokinetic parameters, which uses a nonlinear objective function to efficiently model the measurement noise and utilizes the structural priors to mitigate the ill-posedness of FMT. The results of numerical simulations and in vivo mouse experiments demonstrate that the proposed method leads to significant improvements in the image quality.
Probiotic bacteria are known to exert a wide range of beneficial effects on their animal hosts. Therefore, the present study explored the effect of the supernatants obtained from Lactobacillus delbrueckii fermentation (LBF) on colon cancer. The results indicated that the proliferation of LBF solution-treated colon cancer SW620 cells was arrested and accumulated in the G1 phase in a concentration-dependent manner. The LBF solution efficiently induced apoptosis through the intrinsic caspase 3-depedent pathway, with a corresponding decreased expression of Bcl-2. The activity of matrix metalloproteinase 9, which is associated with the invasion of colon cancer cells, was also decreased in the LBF-treated cells. In conclusion, the results demonstrate the antitumor effect of LBF in vitro and may contribute to the development of novel therapies for the treatment of colon cancer.
Patients with diabetes are at increased risk of ischemic events. Suv39h1 is a histone methyltransferase that catalyzes the methylation of histone 3 lysine 9, which is associated with the suppression of inflammatory genes in diabetes. However, the role of Suv39h1 in myocardial ischemia/reperfusion (I/R) injury under diabetic condition has not been evaluated.
Subsurface fluorescence molecular tomography (FMT) is an emerging technique determining fluorescence distribution by tomographic means in reflectance geometry. However, due to the highly diffusive nature of the photon propagation in biological tissues and the influence of nearer source-detector separations, stand-alone subsurface FMT could not accurately reflect the fluorophore distributions. To overcome this drawback, we propose a method to improve the performance of fluorescence imaging by coupling x-ray computed tomography (XCT) and subsurface FMT modalities. A Laplacian-type regularization matrix generated with tissue prior information obtained from XCT images is used to guide the reconstruction of fluorophore distribution. Reconstruction results of both simulation and phantom studies showed that significant improvements in localization and demarcation of fluorescent targets can be obtained with the proposed method compared to the reconstruction method without structural prior information.
Mesenchymal stem cells (MSCs) have demonstrated promising therapeutic potential for a variety of diseases including autoimmune disorders. A fundamental requirement for MSC-mediated in vivo immunosuppression is their effective trafficking. However the mechanism underlying MSC trafficking remains elusive. Here we report that skin-derived MSCs (S-MSCs) secrete high levels of interleukin-6 (IL-6) in inflammatory conditions. Disruption of the il6 or its signaling transducer gp130 blocks voltage-gated calcium (Ca(2+) ) channels (VGCC) critically required for cell contraction involved in the sequential adhesion and de-adhesion events during S-MSC migration. Deletion of il6 gene leads to a severe defect in S-MSC's trafficking and immunosuppressive function in vivo. Thus, this unexpected requirement of autocrine IL-6 for activating Ca(2+) channels uncovers a previously unrecognized link between the IL-6 signaling and the VGCC and provides novel mechanistic insights for the trafficking and immunomodulatory activities of S-MSCs.
Severely calcified coronary lesions respond poorly to balloon angioplasty, resulting in incomplete and asymmetrical stent expansion. Therefore, adequate plaque modification prior to drug-eluting stent (DES) implantation is the key for calcified lesion treatment. This study was to evaluate the safety and efficacy of cutting balloon angioplasty for severely calcified coronary lesions.
Optical flow (OF) method has been used in ultrasound elastography to estimate the strain distribution in tissues. However the bias of strain estimation by OF has previously been shown to be close to 20%. The objective in this paper is to improve the performance of OF-based strain estimation, a two-step OF method with a local warping technique is proposed in this paper. The local warping technique effectively decreases the decorrelation of the signals, and hence improves the performance of strain estimation. Simulations on both homogeneous and heterogeneous models with different strains are performed. Experiments on a heterogeneous tissue-mimicking phantom are also carried out. Simulation results of the homogeneous model show that the two-step OF method reduces the bias of strain estimation from 23.77% to 1.65%, and reduces the standard deviation of strain estimation from 2.9×10(-3) to 0.47×10(-3). Simulation results of the heterogeneous model shows that the signals-to-noise ratio (SNRe) of strain estimation is improved by 2.1 and 5.3dB in the inclusion and background, respectively, and the contrast-to-noise ratio (CNRe) is improved by 6.8dB. Finally, results of phantom experiments show that, by using the proposed method, the SNRe is increased by 4.0dB and 8.9dB in the inclusion and background, respectively, while the CNRe is increased by 13.1dB. The proposed two-step OF method is thus demonstrated capable of improving the performance of strain estimation in OF-based elastography.
Recent studies demonstrated that nasal polyps (NP) patients in China and other Asian regions possessed distinct Th17-dominant inflammation and enhanced tissue remodeling. However, the mechanism underlying these observations is not fully understood. This study sought to evaluate the association of interleukin (IL)-17A with MUC5AC expression and goblet cell hyperplasia in Chinese NP patients and to characterize the signaling pathway underlying IL-17A-induced MUC5AC expression in vitro.
Dual-modality imaging combines the complementary advantages of different modalities, and offers the prospect of improved preclinical research. The combination of fluorescence imaging and magnetic resonance imaging (MRI) provides cross-validated information and direct comparison between these modalities. Here, we report on the application of a novel tumor-targeted, dual-labeled nanoparticle (NP), utilizing iron oxide as the MRI contrast agent and near infrared (NIR) dye Cy5.5 as the fluorescent agent. Results of in vitro experiments verified the specificity of the NP to tumor cells. In vivo tumor targeting and uptake of the NPs in a mouse model were visualized by fluorescence and MR imaging collected at different time points. Quantitative analysis was carried out to evaluate the efficacy of MRI contrast enhancement. Furthermore, tomographic images were also acquired using both imaging modalities and cross-validated information of tumor location and size between these two modalities was revealed. The results demonstrate that the use of dual-labeled NPs can facilitate the dual-modal detection of tumors, information cross-validation, and direct comparison by combing fluorescence molecular tomography (FMT) and MRI.
Noncompetitive N-methyl-d-aspartate receptor antagonists such as phencyclidine and MK-801 are known to impair cognitive function in rodents and humans, and serve as a useful tool to study the cellular basis for pathogenesis of schizophrenia cognitive symptoms. In the present study, we tested in rats the effect of MK-801 on ventral hippocampus (HPC)-medial prefrontal cortex (mPFC) synaptic transmission and the performance in 2 cognitive tasks. We found that single injection of MK-801 (0.1 mg/kg) induced gradual and long-lasting increases of the HPC-mPFC response, which shares the common expression mechanisms with long-term potentiation (LTP). But unlike LTP, its induction required no enhanced or synchronized synaptic inputs, suggesting aberrant characteristics. In parallel, rats injected with MK-801 showed impairments of mPFC-dependent cognitive flexibility and HPC-mPFC pathway-dependent spatial working memory. The effects of MK-801 on HPC-mPFC responses and spatial working memory decayed in parallel within 24 h. Moreover, the therapeutically important subtype 2/3 metabotropic glutamate receptor agonist LY379268, which blocked MK-801-induced potentiation, ameliorated the MK-801-induced impairment of spatial working memory. Our results show a novel form of use-independent long-lasting potentiation in HPC-mPFC pathway induced by MK-801, which is associated with impairment of HPC-mPFC projection-dependent cognitive function.
Symmetric embedded waveguides were fabricated in heavy metal oxide SF10 glass using slit-shaped infrared femtosecond laser writing in the low-repetition frequency regime. The impact of the writing parameters on the waveguide formation in the transverse writing scheme was systemically studied. Results indicate that efficient waveguides can be inscribed in a wide parameter space ranging from 500 fs to 1.5 ps pulse duration, 0.7-4.2 ?J pulse energy, and 5 ?m/s to 640 ?m/s scan speed and pointing out the robustness of the photoinscription process. The refractive index profile reconstructed from the measured near field pattern goes up to 10(-3). In addition, propagation losses of the waveguides are tolerable, with the lowest propagation loss estimated at 0.7 dB/cm. With a 5 ?m/s scan speed and 3.5 ?J pulse energy in a high-dose regime, few-mode guiding was achieved in the waveguide at 800 nm signal injection wavelength. This is due to a combination of increased refractive index in the core of the trace and the appearance of a depressed cladding.
Glioma is the most common and fatal primary brain tumour with poor prognosis; however, the functional roles of miRNAs in glioma malignant progression are insufficiently understood. Here, we used an integrated approach to identify miRNA functional targets during glioma malignant progression by combining the paired expression profiles of miRNAs and mRNAs across 160 Chinese glioma patients, and further constructed the functional miRNA-mRNA regulatory network. As a result, most tumour-suppressive miRNAs in glioma progression were newly discovered, whose functions were widely involved in gliomagenesis. Moreover, three miRNA signatures, with different combinations of hub miRNAs (regulations?30) were constructed, which could independently predict the survival of patients with all gliomas, high-grade glioma and glioblastoma. Our network-based method increased the ability to identify the prognostic biomarkers, when compared with the traditional method and random conditions. Hsa-miR-524-5p and hsa-miR-628-5p, shared by these three signatures, acted as protective factors and their expression decreased gradually during glioma progression. Functional analysis of these miRNA signatures highlighted their critical roles in cell cycle and cell proliferation in glioblastoma malignant progression, especially hsa-miR-524-5p and hsa-miR-628-5p exhibited dominant regulatory activities. Therefore, network-based biomarkers are expected to be more effective and provide deep insights into the molecular mechanism of glioma malignant progression.
Ultrasound elasticity imaging aims to reconstruct the distribution of elastic modulus (e.g., Youngs modulus) within biological tissues, since the value of elastic modulus is often related to pathological changes. Currently, most elasticity imaging algorithms face a challenge of choosing the value of the regularization constant. We propose a more applicable algorithm without the need of any regularization. This algorithm is not only simple to use, but has a relatively high accuracy. Our method comprises of a nonrigid registration technique and tissue incompressibility assumption to estimate the two-dimensional (2D) displacement field, and finite element method (FEM) to reconstruct the Youngs modulus distribution. Simulation and phantom experiments are performed to evaluate the algorithm. Simulation and phantom results showed that the proposed algorithm can reconstruct the Youngs modulus with an accuracy of 63?85%.
For the ill-posed fluorescent molecular tomography (FMT) inverse problem, the L1 regularization can protect the high-frequency information like edges while effectively reduce the image noise. However, the state-of-the-art L1 regularization-based algorithms for FMT reconstruction are expensive in memory, especially for large-scale problems. An efficient L1 regularization-based reconstruction algorithm based on nonlinear conjugate gradient with restarted strategy is proposed to increase the computational speed with low memory consumption. The reconstruction results from phantom experiments demonstrate that the proposed algorithm can obtain high spatial resolution and high signal-to-noise ratio, as well as high localization accuracy for fluorescence targets.
Multispectral excitation-resolved fluorescence tomography (MEFT) uses excitation light of different wavelengths to illuminate the fluorophores and obtains the reconstruction image frame which is fluorescence yield at each corresponding wavelength. For structures containing fluorophores of different concentrations, fluorescence yields show different variation trends with the excitation spectrum. In this study, principal component analysis (PCA) is used to analyze the MEFT reconstructed image frames. By taking advantage of the different variation trends of fluorescence yields, PCA can provide a set of principal components (PCs) in which structures containing different concentrations of fluorophores are shown separately. Simulations and experiments are both performed to test the performance of the proposed algorithm. The results suggest that the location and structure of fluorophores with different concentrations can be obtained and the contrast of fluorophores can be improved further by using this algorithm.
An efficient synthesis of bifurans via dimerization of cyclopropenes has been successfully developed using a copper-promoted cycloisomerization and palladium-catalyzed dimerization cascade. These novel bifuran structures possess interesting optoelectronic properties.
The high levels of H2O2 are closely associated with cancer and progressive neurodegenerative diseases, such as Parkinsons disease. In this study, we developed a novel CuS nanoparticle-decorated reduced graphene oxide-based electrochemical biosensor for the reliable detection of H2O2. The new electrocatalyst, CuS/RGO composites was successfully prepared by heating the mixture of CuCl2 and Na2S aqueous solutions in the presence of PVP-protected graphene oxide at 180 °C. A potential application of CuS/RGO composite-modified electrode as a biosensor to monitor H2O2 has been investigated. The steady-state current response increases linearly with H2O2 concentration from 5 to 1500 ?M with a fast response time of less than 2 s. The detection limit (3?) for determination of H2O2 has been estimated to be 0.27 ?M, which was lower than certain enzymes and noble metal nanomaterial-based biosensors. In addition, the study of storage time on the amperometric response of the sensor indicates super stability. Due to these remarkable analytical advantages, the as-made sensor was applied to determine the H2O2 levels in human serum and urine samples and H2O2 released from human cervical cancer cells with satisfactory results. These results demonstrate that this new nanocomposite with the high surface area and electrocatalytic activity is a promising candidate for use as an enhanced electrochemical sensing platform in the design of nonenzymatic biosensors.
Double minute chromosomes (DMs) are a hallmark of gene amplification. The relationship between the formation of DMs and the amplification of DM-carried genes remains to be clarified. The human colorectal cancer cell line NCI-H716 and human malignant primitive neuroectodermal tumor cell line SK-PN-DW are known to contain many DMs. To examine the amplification of DM-carried genes in tumor cells, we performed Affymetrix SNP Array 6.0 analyses and verified the regions of amplification in NCI-H716 and SK-PN-DW tumor cells. We identified the amplification regions and the DM-carried genes that were amplified and overexpressed in tumor cells. Using RNA interference, we downregulated seven DM-carried genes, (NDUFB9, MTSS1, NSMCE2, TRIB1, FAM84B, MYC and FGFR2) individually and then investigated the formation of DMs, the amplification of the DM-carried genes, DNA damage and the physiological function of these genes. We found that suppressing the expression of DM-carried genes led to a decrease in the number of DMs and reduced the amplification of the DM-carried genes through the micronuclei expulsion of DMs from the tumor cells. We further detected an increase in the number of ?H2AX foci in the knockdown cells, which provides a strong link between DNA damage and the loss of DMs. In addition, the loss of DMs and the reduced amplification and expression of the DM-carried genes resulted in a decrease in cell proliferation and invasion ability.
In this study, a novel ternary heterojunction n-ZnO/p-Cu2O/n-TiO2 nanotube arrays (n-ZnO/p-Cu2O/n-TNA) nanophotocatalyst with a sandwich-like nanostructure was constructed and applied for the photoelectrocatalytic (PEC) degradation of typical PPCPs, tetracycline (TC). The ternary heterojunction n-ZnO/p-Cu2O/n-TNA was obtained by depositing Cu2O on the surface of TNA via sonoelectrochemical deposition (SED) and subsequently building a layer of ZnO onto the p-Cu2O/n-TNA surface through hydrothermal synthesis. After being deposited by the Cu2O, the absorption-band edge of the p-Cu2O/n-TNA was obviously red-shifted to the visible region (to 505 nm), and the band gap was reduced from its original 3.20 eV to 2.46 eV. The band gap absorption edge of the ternary n-ZnO/p-Cu2O/n-TNA is similar to that of p-Cu2O/n-TN and extends the visible spectrum absorption to 510 nm, corresponding to an Eg value of about 2.43 eV. Under illumination of visible light, the photocurrent density of the ternary heterojunction n-ZnO/p-Cu2O/n-TNA electrode at 0.5 V (vs. Ag/AgCl) was more than 106 times as high as that of the pure TNAs electrode, 3.6 times as high as that of the binary heterojunction p-Cu2O/n-TNA electrode. The degradation of TC indicated that the ternary heterojunction n-ZnO/p-Cu2O/n-TNA electrode maintained a very high photoelectrocatalytic activity and excellent stability and reliability. Such kind of ternary heterojunction electrode material has a broad application prospect not only in pollution control but also in many other fields.
Consumption of a high-fat diet (HFD) is correlated with increased oxidative stress and chronic inflammation in many organs. Regulatory T cells (Tregs) are essential negative regulators of inflammation. We hypothesized that resveratrol (trans-3,5,4-trihydroxystilbene) could protect against HFD-induced oxidative stress and inflammation. Therefore, we examined the effect of resveratrol on oxidative stress and the relevant peripheral immune-regulating mechanisms in HFD-induced obese (DIO) and diet-resistant mice. C57BL/6 mice were fed a normal diet and an HFD for 13 weeks. Then the experimental group was subdivided into DIO and diet-resistant groups according to their body weights, which were further supplemented with 0.03% resveratrol and 0.06% resveratrol, respectively, for an additional 13 weeks. Resveratrol prevented the accumulation of chronic oxidative stress and suppression of Tregs production in HFD mice, modulated changes of cytokines in the plasma and spleen, and decreased expressions of inflammatory mediators compared with those of the DIO group. Our results indicate that resveratrol, as a feasible effective supplement for HFD, can relieve oxidative stress, inhibit inflammatory genes expression, and increase Tregs number via aryl hydrocarbon receptor activation inhibited by HFD, especially in DIO mice.
Increasing evidence suggests seizures cause blood-brain barrier (BBB) dysfunction including decreased seizure threshold and higher onset potential of future seizures. However, the mechanisms underlying BBB damage in seizures remains poorly understood. Evidence in human and animal models shows BBB disruption is associated with activation of matrix metalloproteinase-9 (MMP-9) after cerebral ischemia and inflammation. The objective of this study was to determine whether MMP-9 concentrations in cerebral spinal fluid (CSF) are associated with BBB disruption in patients after epileptic seizures.
The aim of this study was to compare carboprost with oxytocin for the prevention of postpartum hemorrhage (PPH) in females with a high risk of PPH undergoing cesarean delivery. Patients were randomly divided into three groups that received different uterotonics (oxytocin, carboprost and oxytocin plus carboprost) during cesarean section, following the delivery of the infant. A total of 117 females (age range, 19-40 years) at 35-40 weeks gestation who delivered by cesarean between December, 2010 and May, 2012 were included in this study. There were 29 cases of twins, 12 cases of polyhydramnios, 23 cases of placenta previa and 53 cases of fetal macrosomia. There were 37 patients in the oxytocin group, 36 in the carboprost group and 44 in the oxytocin plus carboprost group. No significant differences were identified in maternal age, gravidity/parity, gestational age and reason for cesarean delivery between the three groups. The median blood loss in the oxytocin, carboprost and oxytocin plus carboprost groups was 610, 438 and 520 ml, respectively. The blood loss in the carboprost group was significantly lower than that in the oxytocin and oxytocin plus carboprost groups (both P<0.05). Vomiting occurred in eight patients from the carboprost group, two from the oxytocin group and two from the oxytocin plus carboprost group (P=0.036). Carboprost was more effective than oxytocin in preventing PPH in high-risk patients undergoing cesarean delivery.
The discharge patterns of neurons in auditory centers encode information about sounds. However, few studies have focused on the synaptic mechanisms underlying the shaping of discharge patterns using intracellular recording techniques. Here, we investigated the discharge patterns of inferior collicular (IC) neurons using intracellular recordings to further elucidate the mechanisms underlying the shaping of discharge patterns. Under in vivo intracellular recording conditions, recordings were obtained from 66 IC neurons in 18 healthy adult mice (Mus musculus, Km) under free field-stimulation. Fifty-eight of these neurons fi red bursts of action potentials (APs) to auditory stimuli and the remaining eight just generated local responses such as excitatory (n = 4) or inhibitory (n = 4) postsynaptic potentials. Based on the APs and subthreshold responses, the discharge patterns were classified into seven types: phasic (24/58, 41.4%), phasic burst (8/58,13.8%), pauser (4/58, 6.9%), phasic-pauser (1/58, 1.7%), chopper (2/58, 3.4%), primary-like tonic (14/58, 24.1%) and sound-induced inhibitory (5/58,8.6%). We concluded that (1) IC neurons exhibit at least seven distinct discharge patterns; (2) inhibition participates in shaping the discharge pattern of most IC neurons and plays a role in sculpting the pattern, except for the primary-like tonic pattern which was not shaped by inhibition; and (3) local neural circuits are the likely structural basis that shapes the discharge patterns of IC neurons and can be formed either in the IC or in lower-level auditory structures.
A facile method is presented for the large-scale preparation of rationally designed mesocrystalline MnO@carbon core-shell nanowires with a jointed appearance. The nanostructures have a unique arrangement of internally encapsulated highly oriented and interconnected MnO nanorods and graphitized carbon layers forming an external coating. Based on a comparison and analysis of the crystal structures of MnOOH, Mn2 O3 , and MnO@C, we propose a sequential topotactic transformation of the corresponding precursors to the products. Very interestingly, the individual mesoporous single-crystalline MnO nanorods are strongly interconnected and maintain the same crystallographic orientation, which is a typical feature of mesocrystals. When tested for their applicability to Li-ion batteries (LIB), the MnO@carbon core-shell nanowires showed excellent capacity retention, superior cycling performance, and high rate capability. Specifically, the MnO@carbon core-shell nanostructures could deliver reversible capacities as high as 801?mA?h?g(-1) at a high current density of 500?mA?g(-1) , with excellent electrochemical stability after testing over 200 cycles, indicating their potential application in LIBs. The remarkable electrochemical performance can mainly be attributed to the highly uniform carbon layer around the MnO nanowires, which is not only effective in buffering the structural strain and volume variations of anodes during repeated electrochemical reactions, but also greatly enhances the conductivity of the electrode material. Our results confirm the feasibility of using these rationally designed composite materials for practical applications. The present strategy is simple but very effective, and appears to be sufficiently versatile to be extended to other high-capacity electrode materials with large volume variations and low electrical conductivities.
Direct discharging great quantities of organics into water-body not only causes serious environmental pollution but also wastes energy sources. In this paper, a solar responsive dual photoelectrode photocatalytic fuel cell (PFC(2)) based on TiO2/Ti photoanode and Cu2O/Cu photocathode was designed for hazardous organics treatment with simultaneous electricity generation. Under solar irradiation, the interior bias voltage produced for the Fermi level difference between photoelectrodes drives photoelectrons of TiO2/Ti photoanode to combine with photoholes of Cu2O/Cu photocathode through external circuit thus generating electricity. In the meantime, organics are decomposed by photoholes remained at TiO2/Ti photoanode. By using various hazardous organics including azo dyes as model pollutants, the PFC showed high converting performance of organics into electricity. For example, in 0.05 M phenol solution, a short-circuit current density 0.23 mA cm(-2), open-circuit voltage 0.49 V, maximum power output 0.3610(-4)W cm(-2) was achieved. On the other hand, removal rate of chroma reached 67%, 87% and 63% in 8h for methyl orange, methylene blue, Congo red, respectively.
Levoglucosan is a typical molecular tracer of biomass-burning aerosols in the atmosphere. The mechanism for OH-initiated reaction with levoglucosan is studied at the level of MPWB1K/6-311+G(3df,2p)//MPWB1K/6-31+G(d,p). The possible subsequent reactions in the presence of O2, NO and H2O are also taken into consideration. The study shows that the H atom abstraction from the C4-position by the OH radical is an energetically favorable pathway, and that the OH-initiated products contribute to the formation of SOA and atmospheric acidity. The kinetic calculation is performed and the rate constants are calculated over the temperature range of 200-1500 K, using the Rice-Ramsperger-Kassel-Marcus (RRKM) theory. The rate constant of levoglucosan reacting with the OH radical at 298 K is 2.21×10(-13) cm(3) molecule(-1) s(-1) and the atmospheric lifetime is 26 days ([OH]=2.0×10(6) molecule cm(-3)). The equilibrium constants both in gas phase and aqueous are computed. The free energy ?G indicates that, the subsequent reactions tend to take place more spontaneously once the reaction occurs. This work provides a comprehensive investigation about OH-initiated atmospheric reactions with levoglucosan, which is helpful for experiment and risk assessment.
Microwell technology has revolutionized many aspects of in vitro cellular studies from 2D traditional cultures to 3D in vivo-like functional assays. However, existing lithography-based approaches are often costly and time-consuming. This study presents a rapid, low-cost prototyping method of CO2 laser ablation of a conventional untreated culture dish to create concave microwells used for generating multicellular aggregates, which can be readily available for general laboratories. Polymethylmethacrylate (PMMA), polydimethylsiloxane (PDMS), and polystyrene (PS) microwells are investigated, and each produces distinctive microwell features. Among these three materials, PS cell culture dishes produce the optimal surface smoothness and roundness. A549 lung cancer cells are grown to form cancer aggregates of controllable size from ?40 to ?80 ?m in PS microwells. Functional assays of spheroids are performed to study migration on 2D substrates and in 3D hydrogel conditions as a step towards recapitulating the dissemination of cancer cells. Preclinical anti-cancer drug screening is investigated and reveals considerable differences between 2D and 3D conditions, indicating the importance of assay type as well as the utility of the present approach.
The major O2-insensitive nitroreductase (NfsA) of Escherichia coli shares low sequence homology but similar biochemical and structural features with NfsB, the E. coli minor O2-insensitive nitroreductase. A structural comparison revealed Phe42 was present in the active site of NfsA but not NfsB. F42Y, F42N and F42A were generated and had decreased activity toward nitrofurazone by 52, 96, and 99%, respectively. The kinetic parameters for other nitroaromatic substrates were also determined. Compared to wild type, the mutants did not have significantly altered K(m)s, but had dramatically decreased k(cat) and k(cat)/K(m) values. Far-UV CD spectral analysis of the mutants suggested that there were no significant conformational changes however F42A and F42N had changes from 208 to 222 nm, which was attributed to loss of helix content. These findings revealed that Phe42 is important for maintaining NfsA activity and structure.
Nonviral lipid-based gene delivery vectors have been shown to possess better stability and a longer circulation time after surface poly(ethylene glycol) PEG modification. However, surface PEGylation may decrease the transfection efficiency dramatically. In the present study, we addressed the hypothesis that down-regulating lysosomal processing with a clinical available proton pump inhibitor omeprazole might decrease the sequestration of PEGylated Lipid-Mu-DNA (LMD) in intracellular organelles, thereby increasing their transfection efficiencies.
Congenital cataract is a Mendelian disorder that frequently causes blindness in infants. To date, various cataract-associated loci have been mapped; more than 30 genes have been identified by linkage analysis. However, the pathogenic loci in some affected families are still unknown, and new research strategies are needed. In this study, we used linkage-exome combinational analysis to further investigate the pedigree of a four-generation Chinese family with autosomal dominant coralliform cataract.
The use of doxorubicin (Dox) was severely constrained by dose-dependent side effects, which might be attenuated by combining a "sensitizer" to decrease its cumulative dosage. In this study, it was investigated whether ocotillol could enhance the antiproliferation activity of Dox. MTT assays and xenograft tumor model were firstly conducted to evaluate the effect of ocotillol on the antitumor activity of Dox. Flow cytometry and Hoechst staining assays were then performed to assess cell apoptosis. Western blot and real-time PCR were finally used to detect the expression of p53 and its target genes. Our results showed ocotillol to enhance Dox-induced cell death in p53 wild-type cancer cells. Compared with Dox alone, Dox with ocotillol (Dox-O) could induce much more cell apoptosis and activate p53 to a much greater degree, which in turn markedly increased expression of proapoptosis genes. The enhanced cytotoxic activity was partially blocked by pifithrin- ? , which might be through attenuating the increased apoptosis. Furthermore, ocotillol significantly increased the antitumor activity of Dox in A549 xenograft tumor in nude mice. These findings indicated that ocotillol could potentiate the cytotoxic effect of Dox through p53-dependent apoptosis and suggested that coadministration of ocotillol with Dox might be a potential therapeutic strategy.
Fluorescence molecular tomography (FMT) with early-photons can improve the spatial resolution and fidelity of the reconstructed results. However, its computing scale is always large which limits its applications. In this paper, we introduced an acceleration strategy for the early-photon FMT with graphics processing units (GPUs). According to the procedure, the whole solution of FMT was divided into several modules and the time consumption for each module is studied. In this strategy, two most time consuming modules (Gd and W modules) were accelerated with GPU, respectively, while the other modules remained coded in the Matlab. Several simulation studies with a heterogeneous digital mouse atlas were performed to confirm the performance of the acceleration strategy. The results confirmed the feasibility of the strategy and showed that the processing speed was improved significantly.
Calcium alginate beads are potential biosorbent for radionuclides removal as they contain carboxyl groups. However, until now limited information is available concerning the uptake behavior of uranium by this polymer gel, especially when sorption equilibrium, kinetics and thermodynamics are concerned. In present work, batch experiments were carried out to study the equilibrium, kinetics and thermodynamics of uranium sorption by calcium alginate beads. The effects of initial solution pH, sorbent amount, initial uranium concentration and temperature on uranium sorption were also investigated. The determined optimal conditions were: initial solution pH of 3.0, added sorbent amount of 40 mg, and uranium sorption capacity increased with increasing initial uranium concentration and temperature. Equilibrium data obtained under different temperatures were fitted better with Langmuir model than Freundlich model, uranium sorption was dominated by a monolayer way. The kinetic data can be well depicted by the pseudo-second-order kinetic model. The activation energy derived from Arrhenius equation was 30.0 kJ/mol and the sorption process had a chemical nature. Thermodynamic constants such as ?H(0), ?S(0) and ?G(0) were also evaluated, results of thermodynamic study showed that the sorption process was endothermic and spontaneous.
The aim of the present study was to investigate whether a gradually increasing reperfusion algorithm, in which the brief reperfusion was lengthened as the duration of each reperfusion/reocclusion cycle remained fixed, enhances cardioprotection. Rats were randomized into 5 groups: the sham, reperfusion injury (R/I), gradually decreased reperfusion (GDR; 30/10?25/15?15/25?10/30 sec of reperfusion/reocclusion), equal reperfusion (ER; 4 20/20?sec reperfusion/reocclusion cycles) and gradually increased reperfusion (GIR; 10/30?15/25?25/15?30/10 sec of reperfusion/reocclusion). The rats were sacrificed to measure serum markers, apoptotic indices and infarct size. Western blot analyses were used to analyze the expression of molecules involved in important signaling pathways. All the three postconditioning patterns were found to provide cardioprotection (P<0.05 compared with the R/I group). GIR provided optimum cardioprotection, followed by ER and then GDR. Apoptotic index and serum marker levels were significantly reduced in the GIR compared with the ER group (P<0.05). The enhanced cardioprotection provided by GIR was accompanied by significantly increased levels of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and Bcl?2, as well as lower levels of p38/c?Jun N?terminal kinase (JNK) phosphorylation, tumor necrosis factor ? (TNF?), caspase?8, Bax, caspase?9 and cytochrome c (Cyt?c) in the cytoplasm of rats (P<0.05, all compared with ER). The infarct size in the rats of the GIR group was also smaller compared with that in the rats of the ER group, but this difference was not significant (16.30±5.22 vs. 20.57±6.32%, P>0.05). All the variables measured in the present study were significantly improved in the GIR group compared with the GDR group (P<0.05). In conclusion, the association between brief reperfusion and reocclusion is an important factor in postconditioning algorithms. Additionally, GIR results in improved cardioprotection compared with that achieved by the remaining algorithms examined.
Double minute chromosomes are cytogenetic manifestations of gene amplification frequently seen in cancer cells. Genes amplified on double minute chromosomes include oncogenes and multi-drug resistant genes. These genes encode proteins which contribute to cancer formation, cancer progression, and development of resistance to drugs used in cancer treatment. Elimination of double minute chromosomes, and therefore genes amplified on them, is an effective way to decrease the malignancy of cancer cells. We investigated the effectiveness of a cancer drug, gemcitabine, on the loss of double minute chromosomes from the ovarian cancer cell line UACC-1598. Gemcitabine is able to decrease the number of double minute chromosomes in cells at a 7500X lower concentration than the commonly used cancer drug hydroxyurea. Amplified genes present on the double minute chromosomes are decreased at the DNA level upon gemcitabine treatment. Gemcitabine, even at a low nanomolar concentration, is able to cause DNA damage. The selective incorporation of double minutes chromatin and ?-H2AX signals into micronuclei provides a strong link between DNA damage and the loss of double minute chromosomes from gemcitabine treated cells. Cells treated with gemcitabine also showed decreased cell growth, colony formation, and invasion. Together, our results suggest that gemcitabine is effective in decreasing double minute chromosomes and this affects the biology of ovarian cancer cells.
DNA methylation is an essential epigenetic mechanism involved in transcriptional control. However, how genes with different methylation patterns are assembled in the protein-protein interaction network (PPIN) remains a mystery.
Simultaneous positron emission tomography (PET) and fluorescence tomography (FT) for in vivo imaging of small animals is proposed by a dual-modality system. This system combines a charge-coupled device-based near-infrared fluorescence imaging with a planar detector pair-based PET. With [(18)F]-2-fluoro-2-deoxy-d-glucose radioactive tracer and the protease activated fluorescence probe, on the one hand, the simultaneous metabolic activity and protease activity in tumor region are revealed by the PET and FT, respectively. On the other hand, the protease activity both on the surface layer and the deep tissue of the tumor is provided by the fluorescence reflection imaging and FT, respectively.
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