Ilizarov method in combination with autologous mesenchymal stem cells from iliac crest shows improved outcome in tibial non-union

AbstractAutologous bone grafting and ilizarov technique are the preferred mode of treatment for bone nonunion, studies suggest that bone marrow derived mesenchymal stem cells can be effective in treatment of tibial non-union where there is length of bone defect. The current study investigates the beneficial clinical outcome of combining the ilizarov procedure with intraosseous injection of autologous mesenchymal stem cells. The open-label study enrolled 25 patients with infected tibial non-union at the Shanghai Fengxian District Central Hospital, Shanghai, China between April 2010 and July 2014. Patients were randomised to undergo the ilizarov procedure with (n=11) or without (n=13) intraosseous injection of bone marrow derived mesenchymal stem cells. All participants were followed prospectively until union was achieved (primary end point). The mean length of the bone defect in the Ilizarov group and Ilizarov group plus MSC group was 6.09 and 5.84cm respectively. The mean time from the original injury to the time of the treatment for tibial non-union was 5–22months (mean 13.5months) for the Ilizarov group and 6–21months (mean 13.5months) for Ilizarov plus MSc group. All 24 patients were followed up for 12–34months (mean 16months). Both groups achieved the primary endpoint of stable union of the tibial fracture. No adverse events were observed in any of the group. Our study demonstrates that using autologous bone marrow derived mesenchymal stem cell as an add-on therapy to the ilizarov procedure shows significant clinical benefit in fixation of tibial non-union

Comparative transcriptome analysis and marker development of two closely related Primrose species (Primula poissonii and Primula wilsonii)

BACKGROUND: Primula species are important early spring garden plants with a centre of diversity and speciation in the East Himalaya-Hengduan Mountains in Western China. Studies on population genetics, speciation and phylogeny of Primula have been impeded by a lack of genomic resources. In the present study, we sequenced the transcriptomes of two closely related primrose species, Primula poissonii and Primula wilsonii, using short reads on the Illumina Genome Analyzer platform. RESULTS: We obtained 55,284 and 55,011 contigs with N50 values of 938 and 1,085 for P. poissonii and P. wilsonii, respectively, and 6,654 pairs of putative orthologs were identified between the two species. Estimations of non-synonymous/synonymous substitution rate ratios for these orthologs indicated that 877 of the pairs may be under positive selection (Ka/Ks > 0.5), and functional enrichment analysis revealed that significant proportions of the orthologs were in the categories DNA repair, stress resistance, which may provide some hints as to how the two closely related Primula species adapted differentially to extreme environments, such as habitats characterized by aridity, high altitude and high levels of ionizing radiation. It was possible for the first time to estimate the divergence time between the radiated species pair, P. poissonii and P. wilsonii; this was found to be approximately 0.90 ± 0.57 Mya, which falls between the Donau and Gunz glaciation in the Middle Pleistocene. Primers based on 54 pairs of orthologous SSR-containing sequences between the two Primula species were designed and verified. About half of these pairs successfully amplified for both species. Of the 959 single copy nuclear genes shared by four model plants (known as APVO genes), 111 single copy nuclear genes were verified as being present in both Primula species and exon-anchored and intron-spanned primers were designed for use. CONCLUSION: We characterized the transcriptomes for the two Primula species, and produced an unprecedented amount of genomic resources for these important garden plants. Evolutionary analysis of these two Primula species not only revealed a more precise divergence time, but also provided some novel insights into how differential adaptations occurred in extreme habitats. Furthermore, we developed two sets of genetic markers, single copy nuclear genes and nuclear microsatellites (EST-SSR). Both these sets of markers will facilitate studies on the genetic improvement, population genetics and phylogenetics of this rapidly adapting taxon

Time and Antigen-Stimulation History Influence Memory CD8 T Cell Bystander Responses

Memory CD8 T cells can be activated and induced to produce cytokines and increase stores of cytolytic proteins not only in response to cognate antigen (Ag) but also in response to inflammatory cytokines (bystander responses). Importantly, bystander memory CD8 T cell functions have been shown to be dependent upon memory CD8 T cell fitness, since exhausted CD8 T cells have diminished capacity to respond to inflammatory cues. While it is known that memory CD8 T cell functional abilities, including ability to produce cytokines in response to cognate Ag, change with time after initial Ag encounter and upon multiple Ag stimulations (e.g., primary vs. tertiary CD8 T cell responses), it is unknown if bystander memory CD8 T cell responses are influenced by time or by Ag-exposure history. Here, we examined time and Ag-stimulation history-dependent alterations in virus-specific memory CD8 T cell bystander functions in response to inflammatory cytokines and unrelated bacterial infection. We found that expression of cytokine receptors and ability to produce IFN-γ following heterologous infection or incubation with inflammatory cytokines decreases with time following initial Ag encounter and increases with additional Ag encounters, suggesting that the ability to sense inflammation and respond with bystander cytokine production is dependent on age and Ag-stimulation history of memory CD8 T cells. These data shed further light on the regulation of memory CD8 T cell effector functions and have important implications for the development of vaccines designed to elicit protective memory CD8 T cells

Research Progress and Outlook of Food Grade Rice Bran

This paper reviews the nutrition and utilization of rice bran and the future development of food grade rice bran. Rice bran has high nutritional value and rich biological activities. The utilization of rice bran fiber is mainly through modification. The combination of physical and enzymatic methods and supercritical CO2 treatment are beneficial to improve the soluble dietary fiber content and fiber extraction rate. The utilization of rice bran protein includes extraction and modification. The study of extraction of rice bran protein focuses on the combination of physical and enzymatic methods. Moreover, subcritical water, which is a new green extraction technology, has gradually become a research hotspot. The rice bran protein is mainly modified using enzymatic method to improve the function and biological activity of the protein. Therefore,studies on the development of food grade rice bran will be a trend in the future

TCF1 and LEF1 Control Treg Competitive Survival and Tfr Development to Prevent Autoimmune Diseases.

CD4+ Foxp3+ T regulatory (Treg) cells are key players in preventing lethal autoimmunity. Tregs undertake differentiation processes and acquire diverse functional properties. However, how Treg's differentiation and functional specification are regulated remains incompletely understood. Here, we report that gradient expression of TCF1 and LEF1 distinguishes Tregs into three distinct subpopulations, particularly highlighting a subset of activated Treg (aTreg) cells. Treg-specific ablation of TCF1 and LEF1 renders the mice susceptible to systemic autoimmunity. TCF1 and LEF1 are dispensable for Treg's suppressive capacity but essential for maintaining a normal aTreg pool and promoting Treg's competitive survival. As a consequence, the development of T follicular regulatory (Tfr) cells, which are a subset of aTreg, is abolished in TCF1/LEF1-conditional knockout mice, leading to unrestrained T follicular helper (Tfh) and germinal center B cell responses. Thus, TCF1 and LEF1 act redundantly to control the maintenance and functional specification of Treg subsets to prevent autoimmunity

In vitro evaluation of anticancer nanomedicines based on doxorubicin and amphiphilic Y-shaped copolymers

Four monomethoxy poly(ethylene glycol)-poly(L-lactide-co-glycolide)2 (mPEG-P( LA-co-GA)2) copolymers were synthesized by ring-opening polymerization of L-lactide and glycolide with double hydroxyl functionalized mPEG (mPEG-(OH)2) as macroinitiator and stannous octoate as catalyst. The copolymers self-assembled into nanoscale micellar/vesicular aggregations in phosphate buffer at pH 7.4. Doxorubicin (DOX), an anthracycline anticancer drug, was loaded into the micellar/vesicular nanoparticles, yielding micellar/vesicular nanomedicines. The in vitro release behaviors could be adjusted by content of hydrophobic polyester and pH of the release medium. In vitro cell experiments showed that the intracellular DOX release could be adjusted by content of P(LA-co-GA), and the nanomedicines displayed effective proliferation inhibition against Henrietta Lacks’s cells with different culture times. Hemolysis tests indicated that the copolymers were hemocompatible, and the presence of copolymers could reduce the hemolysis ratio of DOX significantly. These results suggested that the novel anticancer nanomedicines based on DOX and amphiphilic Y-shaped copolymers were attractive candidates as tumor tissular and intracellular targeting drug delivery systems in vivo, with enhanced stability during circulation and accelerated drug release at the target sites

Dual-energy computed tomography iodine uptake in differential diagnosis of inflammatory and malignant pulmonary nodules

PURPOSEThe aim of this study was to evaluate the diagnostic performance of iodine uptake parameters using dual-energy computed tomography (DECT) in discriminating inflammatory nodules from malignant tumors.METHODSThis retrospective study included 116 solid pulmonary nodules from 112 patients who were admitted to our hospital between January and September 2018. All nodules were confirmed by surgery or puncture. The degree of enhancement of a single-section region of interest was evaluated. After total tumor volume-of-interest segmentation, the mean iodine density of the whole tumor was measured. Meanwhile, iodine uptake parameters, including total iodine uptake volume, total iodine concentration, vital iodine uptake volume, and vital iodine concentration, were calculated, and a predictive model was established. The overall ability to discriminate between inflammatory and malignant nodules was analyzed using an independent samples t-test for normally distributed variables. The diagnostic accuracy and prognostic performance of DECT parameters were evaluated and compared using receiver operating characteristic curve analysis and logistic regression analysis. A multivariate logistic regression analysis was used to determine the prognostic factors and goodness-of-fit of the whole tumor mean iodine and iodine uptake parameters for discriminating malignant nodules.RESULTSThere were 116 non-calcified nodules, including 64 inflammatory nodules and 52 malignant nodules. The degree of enhancement in malignant nodules was significantly lower than that in inflammatory nodules (P=.043). All iodine uptake parameters in malignant nodules were significantly higher than those in inflammatory nodules (P < .001). The area under the receiver operating curve value, accuracy, sensitivity, and specificity of the established model based on iodine uptake parameters were 0.803, 76.72%, 82.69%, and 84.37%, respectively, which exhibited better diagnostic performance than the degree of enhancement on weighted average images with respective values of 0.609, 59.48%, 61.54%, and 59.38%.CONCLUSIONThe iodine uptake parameters of DECT exhibited better diagnostic accuracy in discriminating inflammatory nodules from malignant nodules than the degree of enhancement on weighted average images