Explore the vast range of titles available.

Reactive oxygen species (ROS) play vital roles in intestinal inflammation. Therefore, eliminating ROS in the inflammatory site by antioxidant enzymes such as catalase and superoxide dismutase may effectively curb inflammatory bowel disease (IBD). Here, Escherichia coli Nissle 1917 (ECN), a kind of oral probiotic, was genetically engineered to overexpress catalase and superoxide dismutase (ECN-pE) for the treatment of intestinal inflammation. To improve the bioavailability of ECN-pE in the gastrointestinal tract, chitosan and sodium alginate, effective biofilms, were used to coat ECN-pE via a layer-by-layer electrostatic self-assembly strategy. In a mouse IBD model induced by different chemical drugs, chitosan/sodium alginate coating ECN-pE (ECN-pE(C/A) 2 ) effectively relieved inflammation and repaired epithelial barriers in the colon. Unexpectedly, such engineered EcN-pE(C/A) 2 could also regulate the intestinal microbial communities and improve the abundance of Lachnospiraceae _NK4A136 and Odoribacter in the intestinal flora, which are important microbes to maintain intestinal homeostasis. Thus, this study lays a foundation for the development of living therapeutic proteins using probiotics to treat intestinal-related diseases. Inflammatory bowel disease (IBD) is a complex disease that is associated with multiple genetic and environmental variables. Here the authors develop genetically engineered probiotics with selfproducing functional proteins and biofilm self-coating for safe and efficient IBD treatment in mice.

The survival of cancer stem cells is usually limited to a specific tumor microenvironment, and this microenvironment plays a vital role in the development of tumors. The mechanical properties of the microenvironment differ in different regions of solid tumors. However, in solid tumors, whether the distribution of cancer stem cells relates to the mechanical microenvironment of different regions is still unclear. In this study, we undertook a biophysical and biochemical assessment of the changes in the mechanical properties of liver tissue during the progression of liver cancer and explored the distribution of liver cancer stem cells in liver cancer tissues. Our analysis confirmed previous observations that the stiffness of liver tissue gradually increased with the progress of fibrosis. In liver cancer tissues, we found obvious mechanical heterogeneity: the core of the tumor was soft, the invasive front tissue was the hardest, and the para-cancer tissue was in an intermediate state. Interestingly, the greatest number of liver cancer stem cells was found in the invasive front part of the tumor. We finally established that stroma stiffness correlated with the number of liver cancer stem cells. These findings indicate that the distribution of liver cancer stem cells correlates with the mechanical heterogeneity of liver cancer tissue. This result provides a theoretical basis for the development of targeted therapies against the mechanical microenvironment of liver cancer stem cells.

KEY MESSAGE : Ion beam mutations can be efficiently isolated and deployed for functional comparison of homoeologous loci in polyploid plants, and Glu - 1 loci differ substantially in their contribution to wheat gluten functionality. To efficiently conduct genetic analysis, it is beneficial to have multiple types of mutants for the genes under investigation. Here, we demonstrate that ion beam-induced deletion mutants can be efficiently isolated for comparing the function of homoeologous loci of common wheat (Triticum aestivum). Through fragment analysis of PCR products from M₂ plants, ion beam mutants lacking homoeologous Glu-A1, Glu-B1 or Glu-D1 loci, which encode high molecular weight glutenin subunits (HMW-GSs) and affect gluten functionality and end-use quality of common wheat, could be isolated simultaneously. Three deletion lines missing Glu-A1, Glu-B1 or Glu-D1 were developed from the original mutants, with the Glu-1 genomic regions deleted in these lines estimated using newly developed DNA markers. Apart from lacking the target HMW-GSs, the three lines all showed decreased accumulation of low molecular weight glutenin subunits (LMW-GSs) and increased amounts of gliadins. Based on the test data of five gluten and glutenin macropolymer (GMP) parameters obtained with grain samples harvested from two environments, we conclude that the genetic effects of Glu-1 loci on gluten functionality can be ranked as Glu-D1 > Glu-B1 > Glu-A1. Furthermore, it is suggested that Glu-1 loci contribute to gluten functionality both directly (by promoting the formation of GMP) and indirectly (through keeping the balance among HMW-GSs, LMW-GSs and gliadins). Finally, the efficient isolation of ion beam mutations for functional comparison of homoeologous loci in polyploid plants and the usefulness of Glu-1 deletion lines for further studying the contribution of Glu-1 loci to gluten functionality are discussed.

ObjectivesTo investigate the impact of secreted factors of rat bone marrow mesenchymal stem cells (MSCs) on the proliferation and migration of tenocytes and provide evidence for the development of MSC-based therapeutic methods of tendon injury.ResultsRat bone marrow mesenchymal stem cell-derived conditioned medium (MSC-CM) promoted the proliferation of tenocytes within 24 h and decreased the percentage of tenocytes in G1 phase. MSC-CM activated the extracellular signal-regulated kinase1/2 (ERK1/2) signal molecules, while the ERK1/2 inhibitor PD98059 abrogated the MSC-CM-induced proliferation of tenocytes, decreased the fraction of tenocytes in the G1 phase and elevated p-ERK1/2 expression. Furthermore, MSC-CM promoted the migration of tenocytes within 6 h, enhanced the formation of filamentous actin (F-actin) and increased the cellular and nuclear stiffness of tenocytes.ConclusionsMSC-CM promotes tenocyte proliferation by changing cell cycle distribution via the ERK1/2 signaling pathway. MSC-CM-induced tenocyte migration was accompanied by cytoskeletal polymerization and increases in cellular and nuclear stiffness.

Shenmai injection is mainly used for the treatment of heart-related diseases, including coronary heart disease, viral myocarditis, chronic cor pulmonale, and shock in Asia. Medicinal materials from different origins produce Shenmai injections for clinical use, and their protective effects on cardiomyocytes may vary with the choice of raw materials. In this study, we compared the protective effects of Shenmai injections produced from different raw materials on cardiomyocytes. Results showed that the protective effects of various Shenmai injections on hypoxia-reoxygenation-induced cardiomyocyte injury were mainly attributed to total ginsenosides extract, with few differences between them. However, the protective effects of different Shenmai injections on doxorubicin and oxidative stress-induced cardiomyocyte injury were significantly different; the protective effects of Shenmai injection with Zhejiang Ophiopogon japonicus as raw material were significantly better than those with Sichuan Ophiopogon japonicus, consistent with our previous research results. Our study reveals the different cardiomyocyte protective effects of Shenmai injections produced by medicinal materials from different origins, laying a scientific foundation for their clinical selection.

AbstractModern molecular techniques have highlighted the presence of inflammation throughout the spectrum of tendinopathy. Previous studies have suggested that excessive inflammation in the tendon is a major factor leading to poor clinical treatment. Furthermore, the NLRP3 inflammasome, as a new term, is closely associated with the pathogenesis of many diseases. In the present study, we examined whether the NLRP3 inflammasome contributes to the development of tendinitis and whether cyclic stretching plays a prominent role in inflammation in the tendon. In the present study, we showed that hydrogen peroxide (H2O2) remarkably enhances the expression and release of IL-1β, TNF-α, and IL-6. The maturation of IL-1β, induced by H2O2, depends on the activation of the NLRP3 inflammasome. Cyclic stretching enhances the maturation of IL-1β via promoting H2O2-induced NLRP3 inflammasome activation in tenocytes. Furthermore, we also found that the depolymerization of filamentous actin (F-actin) was required for cyclic stretching-enhanced NLRP3 inflammasome activation. The present study suggests that NLRP3 inflammasome plays an important regulatory role in the pathogenesis of tendinitis. Disruption of the cytoskeleton by cyclic stretching exerts a proinflammatory effect via further activating the NLRP3/IL-1β pathway and hence contributes to tendinitis. These results may provide theoretical support for a new treatment strategy for preventing excessive inflammation in the tendon.

The clinical application of EGFR tyrosine kinase inhibitors is always accompanied by inevitable drug resistance. However, the mechanism remains elusive. In the present study, we investigate the involvement of MAPK/SREBP1 pathway in NSCLC gefitinib resistance and evaluate the synergistic effects of shenqi fuzheng injection (SFI) and gefitinib on NSCLC cells. To investigate the MAPK/SREBP1 pathway involved in gefitinib resistance, Western blotting was used to examine p-MEK, p-ERK and SREBP1 expression in PC-9 and PC-9/GR cells, MTT was used on cell proliferation, wound healing assay was used on cell migration. To detect the cooperative effects of SFI and gefitinib, clonogenic assay was used on cell proliferation. Apoptosis assay was analyzed by flow cytometry. Immunofluorescence was used to detect gefitinib binding to EGFR. Western blotting was used to detect whether SFI regulate the resistance to gefitinib via the suppression of MAPK/SREBP1 pathway. Our results showed that MAPK/SREBP1 pathway mediated resistance to gefitinib in NSCLC cells. MAPK pathway was found to directly target SREBP1 and inhibition of SREBP1 increased gefitinib sensitivity. In addition, SFI showed cooperative anti-proliferation and pro-apoptosis impacts on gefitinib resistant cells via down-regulating MAPK/SREBP1 pathway. Moreover, the combination of SFI and gefitinib enhanced gefitinib binding to EGFR resulting in the restoration of sensitivity to gefitinib. Taken together, MAPK/SREBP1 pathway could be regarded as the potential treatment target for overcoming resistance to EGFR-TKIs in NSCLC and adjuvant therapy of SFI could be a potential therapeutic strategy for gefitinib resistant treatment.

Although gefitinib brings about tremendous advances in the treatment of non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations, most of patients become incurable due to drug resistance. JuBei oral liquid (JB) has been widely used to treat pneumonia in clinic. Components of JB were reported to induce apoptosis in NSCLC, which indicated that JB could be a potential antitumor agent for NSCLC patients. In this study, we investigated the effect of JB on gefitinib-sensitive PC-9 and gefitinib-resistant PC-9/GR, H1975 cells as well as its underlying molecular mechanisms. PC-9, PC-9/GR and H1975 cells were treated with JB, LY294002, SCH772984, gefitinib alone or in combination. Then, cell viability, colony formation, cell death, expression of mitochondria-dependent pathway proteins, expression of EGFR, PI3K/AKT, MAPK signal pathway proteins, Bcl-2 mitochondrial translocation, ROS generation and cell apoptosis were examined by MTT, colony forming, live/dead cell staining, Western blot, immunofluorescence and flow cytometry assay. Our results showed that JB significantly induced cell growth inhibition and apoptotic cell death in PC-9, PC-9/GR and H1975 cells. JB activated mitochondria-mediated apoptotic pathway through inhibiting Bcl-2 mitochondrial translocation while inducing Bax translocated into mitochondria along with accumulated ROS production, thereby increasing the release of cytochrome c, subsequently cleaving procaspase9 into cleaved-caspase9 and then cleaving procaspase3 into cleaved-caspase3. Furthermore, the employment of protein kinase inhibitors LY294002 and SCH772984 revealed that the induction of mitochondria-mediated apoptosis by JB was reliant on inactivation of PI3K/AKT and MAPK signal pathways. Moreover, JB could synergize with gefitinib to induce apoptosis in PC-9, PC-9/GR and H1975 cells. These data indicated that JB could be a potential therapeutic agent for NSCLC patients harboring EGFR mutations as well as those under gefitinib resistance.

The current knowledge of the transcriptome is limited to understand the exact molecular mechanism of the ion-implantation biological effects on cereals. In order to investigating the overall characteristics of the transcript profiles associated with these puzzling biological effects. We used the Agilent Rice Oligo Microarray （4×44K）Genome Array to learn the molecular mechanism in rice responding to ion-implantation. Rice seeds were implanted by the Nitrogen ion beam and their vigor index was investigated at ten days after germination. Total RNAs was extracted from the rice seedlings at 96 hour after germination and hybridized by the genome genechip. The results of measuring of the vigor index showed that lower-dose implantation of the nitrogen ion beam (6×1017 N+/cm2) promoted the vigor index of the rice seedlings and the higher-dose implantation (9×1017 N+/cm2) damaged the rice seedlings because of the smaller vigor index than the control. The analysis of the genechip array showed that there were 982 transcripts expressed differentially (fold change＞2 and P value＜0.05) including 429 up-regulated transcripts and 553 down-regulated transcripts under the dose3 6×1017 N+/cm2. 30 out of the 553 down-regulated transcripts were involved in 48 pathways. 14 out of these 30 transcripts were associated with more than two interrelated pathways. Os04g0518400 (Phenylalanine ammonia-lyase 2 (PAL; EC 4.3.1.5; down-regulated 3.3 folds; p value=0.005) were involved in 7 pathways, Os07g0446800 (Hexokinase; dwon-regulated 2.8 folds; p value =0.006) were involved in 12 pathways, and Os02g0730000 (Mitochondrial aldehyde dehydrogenase ALDH2a; down-regulated 2.2 folds; p value=0.019) were involved in 13 pathways. These results revealed that down-regulated genes involving important pathways were compatible with the distinct cellular events in response to implantation of low-energy ion beam and supplied the first comprehensive and comparative molecular information for further understanding the mechanism underlying implantation of the low-energy nitrogen ion beam.