The erythroblastic island (EBI), composed of a central macrophage and surrounding erythroid cells, was the first hematopoietic niche discovered. The identity of EBI macrophages has thus far remained elusive. Given that Epo is essential for erythropoiesis and that Epor is expressed in numerous nonerythroid cells, we hypothesized that EBI macrophages express Epor so that Epo can act on both erythroid cells and EBI macrophages simultaneously to ensure efficient erythropoiesis. To test this notion, we used Epor-eGFPcre knockin mouse model. We show that in bone marrow (BM) and fetal liver, a subset of macrophages express Epor-eGFP. Imaging flow cytometry analyses revealed that >90% of native EBIs comprised F4/80+Epor-eGFP+ macrophages. Human fetal liver EBIs also comprised EPOR+ macrophages. Gene expression profiles of BM F4/80+Epor-eGFP+ macrophages suggest a specialized function in supporting erythropoiesis. Molecules known to be important for EBI macrophage function such as Vcam1, CD169, Mertk, and Dnase2α were highly expressed in F4/80+Epor-eGFP+ macrophages compared with F4/80+Epor-eGFP− macrophages. Key molecules involved in iron recycling were also highly expressed in BM F4/80+Epor-eGFP+ macrophages, suggesting that EBI macrophages may provide an iron source for erythropoiesis within this niche. Thus, we have characterized EBI macrophages in mouse and man. Our findings provide important resources for future studies of EBI macrophage function during normal as well as disordered erythropoiesis in hematologic diseases such as thalassemia, polycythemia vera, and myelodysplastic syndromes.

Chitin was purified from Penaeus monodon and Crangon crangon shells using a two-stage fermentation process with anaerobic deproteination followed by decalcification through homofermentative lactic acid fermentation. Deproteinating enrichment cultures from sewage sludge and ground meat (GM) were used with a proteolytic activity of 59 and 61 mg N l(-1) h(-1) with dried and 26 and 35 mg N l(-1) h(-1) with wet P. monodon shells. With 100 g wet cells of proteolytic bacteria per liter, protein removal was obtained in 42 h. An anaerobic spore-forming bacterium HP1 was isolated from enrichment GM. Its proteolytic activity was 76 U ml(-1) compared to 44 U ml(-1) of the consortium. Glucose was fermented with Lactobacillus casei MRS1 to lactic acid. At a pH of 3.6, calcium carbonate of the shells was solubilised. After deproteination and decalcification of P. monodon or C. crangon shells, the protein content was 5.8% or 6.7%, and the calcium content was 0.3% or 0.4%, respectively. The viscosity of the chitin from P. monodon and C. crangon was 45 and 135 mPa s, respectively, whereas purchased crab shell chitin (practical grade) had a viscosity of 21 mPa s, indicating a higher quality of biologically purified chitin.

BackgroundFor the study, we determine the potential biomarkers and uncover the regulatory mechanisms of lncRNA MALAT1 / miR-145 / SOX9 axis on the abilities of cell growth and cell metastasis of colorectal cancer.MethodsPreviously published dataset GSE18105 from GEO database was used for microarray analysis to identify differential-expressed lncRNAs and mRNAs. The miRNA which had targeted relationships with both lncRNA and mRNA was predicted using miRCode and Targetscan. The association between lncRNA and miRNA, miRNA and mRNA was verified using dual-luciferase reporter assay.Expression levels of lncRNA MALAT1, miR-145 and SOX9 were examined by quantitative RT-PCR analysis. The cell viability of two cancer cell lines was compared by CCK-8 assay. Colony formation was hired to detected cell proliferation. The cell cycle distribution and apoptotic cell rate were conducted by flow cytometry assay. Wound healing as well as transwell assay were compare the cell migration and cell invasion respectively among groups. The effect of MALAT1 on colorectal cancer in vivo was constructed by xenograft model.ResultsSignificantly dysregulated lncRNAs and mRNAs were identified by microarray analysis. By experimental verification, MALAT1 and SOX9 were expressed in a high percentage of colorectal cancer tumors and cells, while miR-145 was in a low expression. We also identified miR-145 as a target of MALAT1 and SOX9. MALAT1 played a role in regulating cancer process by functioning as a competing endogenous RNA. Silencing MALAT1 could effectively decrease the expression level of SOX9, thus suppress cell viability and metastasis. Down-regulated MALAT1 could induce resistance of G1 phase in cell cycle, and facilitation of colorectal cancer cell apoptosis. Nude mice injected with cells transfected with si-MALAT1 had smaller tumor on size and weight.ConclusionsThe regulatory function of lncRNA MALAT1 / miR-145 / SOX9 axis was revealed in colorectal cancer based on bioinformatics analysis. LncRNA MALAT1 could facilitate colorectal cancer cell proliferation, invasion and migration by down-regulating miR-145 and up-regulating SOX9. LncRNA MALAT1 could suppress cell cycle and apoptosis through MALAT1 / miR-145 / SOX9 axis.

Due to the adverse effects of erythropoietin (EPO) on cancer patient survival, it is necessary to develop new agents that can be used to efficiently manage and treat cancer‐related anemia. In this study, novel distinctive carbon dots, J‐CDs, derived from jujube are designed, synthesized, and characterized. Based on the obtained results, this material comprises sp2 and sp3 carbon atoms, as well as oxygen/nitrogen‐based groups, and it specifically promotes the proliferation of erythroid cells by stimulating the self‐renewal of erythroid progenitor cells in vitro and in vivo. Moreover, J‐CDs have no discernible effects on tumor proliferation and metastasis, unlike EPO. Transcriptome profiling suggests that J‐CDs upregulate the molecules involved in hypoxia response, and they also significantly increase the phosphorylation levels of STAT5, the major transducer of signals for erythroid progenitor cell proliferation. Overall, this study demonstrates that J‐CDs effectively promote erythrocyte production without affecting tumor proliferation and metastasis; thus, they may be promising agents for the treatment of cancer‐related anemia.

Background Triple-negative breast cancer (TNBC) is a highly aggressive malignant disease with a high rate of recurrence and metastasis, few effective treatment options and poor prognosis. Here, we designed and constructed a combined photothermal immunotherapy strategy based on cancer cell membrane-coated biomimetic black phosphorus quantum dots (BBPQDs) for tumor-targeted photothermal therapy and anti-PD-L1 mediated immunotherapy. Results BBPQDs have good photothermal conversion efficiency and can efficiently target tumor cells through homologous targeting and tumor homing. Under near infrared irradiation, we found that BBPQDs kill tumors directly through photothermal effects and induce dendritic cells maturation. In vivo studies have confirmed that the combined photothermal immunotherapy strategy displays a stronger antitumor activity than anti-PD-L1 monotherapy. In addition, BBPQDs-mediated photothermal therapy in combination with anti-PD-L1 treatment inhibit tumor recurrence and metastasis by reprograming the immunosuppressive tumor microenvironment into an immune-active microenvironment, and promoting the local and systemic antitumor immune response. We further found that the combined photothermal immunotherapy strategy can produce an immune memory effect against tumor rechallenge. Conclusions This study provides a novel therapeutic strategy for inhibiting the recurrence and metastasis of TNBC, with broad application prospects.

Relatively little information is available on quantitative risks of therapy-induced second malignant neoplasm (SMN) in patients with non-Hodgkin lymphoma (NHL). A nested case-control study was conducted in a cohort of 3412 patients treated for NHL between 1990 and 2006, including 118 patients with SMN and 472 controls. Risks of leukemia/lung/breast/colorectal and bladder cancer were higher in NHL compared with the general population. A higher risk of leukemia was restricted to patients given a cumulative dose of cyclophosphamide more than 11 250 mg/m(2). However, no significant association was found between SMN risk with rituximab, fludarabine, anthracyclines, epipodophyllotoxins and platinum, respectively. In combined modality treatment, involved-field radiation therapy (IFRT) had a higher risk for second solid cancers as compared to involved-nodal radiation therapy (INRT). For patients receiving radiation doses exceeding 40 Gy, the risk of lung cancer and breast cancer was increased. In conclusion, we found that cyclophosphamide-based therapy increased the risk of SMN in NHL. Leukemia risk was linked with high-dose cyclophosphamide. A received larger radiation field or higher radiation dose also could be an important risk factor for the development of SMN.

The aim of this study was to correlate matrix metalloproteinase-2 and matrix metalloproteinase-9 expression with the clinicopathological features and outcome of patients with early gastric cancer and to clinically elucidate more information on the role of matrix metalloproteinase-2 and matrix metalloproteinase-9 protein overexpression with regard to lymph node metastasis of early gastric cancer. The levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 protein expression were assessed by immunohistochemistry. An association was observed between matrix metalloproteinase-2, matrix metalloproteinase-9, and matrix metalloproteinase-2/matrix metalloproteinase-9 overexpression and clinicopathological factors, such as ulceration and lymph node metastasis. Furthermore, matrix metalloproteinase-9 and matrix metalloproteinase-2/matrix metalloproteinase-9 overexpression both were strongly correlated with histological grade. In addition, matrix metalloproteinase-2/matrix metalloproteinase-9 overexpression correlated with deep invasion. Multivariate Cox regression analysis revealed that matrix metalloproteinase-2 and matrix metalloproteinase-9 expression were both independent factors of overall survival in patients with early gastric cancer. In novelty, we found that matrix metalloproteinase-2/matrix metalloproteinase-9 overexpression was an independent indicator of lymph node metastasis in early gastric cancer which will be helpful in clinic to select the appropriate treatment of these patients.

BackgroundAfter cellulose and starch, chitin is the third-most abundant biopolymer on earth. Chitin or its deacetylated derivative chitosan is a valuable product with a number of applications. It is one of the main components of shrimp shells, a waste product of the fish industry. To obtain chitin from Penaeus monodon, wet and dried shrimp shells were deproteinated with two specifically enriched proteolytic cultures M1 and M2 and decalcified by in-situ lactic acid forming microorganisms. The viscosity of biologically processed chitin was compared with chemically processed chitin. The former was further investigated for purity, structure and elemental composition by several microscopic techniques and 13C solid state NMR spectroscopy.ResultsAbout 95% of the protein of wet shrimp shells was removed by proteolytic enrichment culture M2 in 68 h. Subsequent decalcification by lactic acid bacteria (LAB) took 48 h. Deproteination of the same amount of dried shrimps that contained a 3 × higher solid content by the same culture was a little bit faster and was finished after 140 h. The viscosity of chitin was in the order of chemically processed chitin > bioprocessed chitin > commercially available chitin. Results revealed changes in fine structure and chemical composition of the epi-, exo- and endocuticle of chitin from shrimp shells during microbial deproteination and demineralization. From transmission electron microscopy (TEM) overlays and electron energy loss spectroscopy (EELS) analysis, it was found that most protein was present in the exocuticle, whereas most chitin was present in the endocuticle. The calcium content was higher in the endocuticle than in the exocuticle.13C solid state NMR spectra of different chitin confirmed < 3% impurities in the final product.ConclusionsBioprocessing of shrimp shell waste resulted in a chitin with high purity. Its viscosity was higher than that of commercially available chitin but lower than that of chemically prepared chitin in our lab. Nevertheless, the biologically processed chitin is a promising alternative for less viscous commercially available chitin. Highly viscous chitin could be generated by our chemical method. Comprehensive structural analyses revealed the distribution of the protein and Ca matrix within the shrimp shell cuticle which might be helpful in developing shrimp waste processing techniques.