Macrophages (Mphi) are prominent components of solid tumors and exhibit distinct phenotypes in different microenvironments. We have recently found that tumors can alter the normal developmental ...process of Mphi to trigger transient activation of monocytes in peritumoral stroma. We showed that a fraction of monocytes/Mphi in peritumoral stroma, but not in cancer nests, expresses surface PD-L1 (also termed B7-H1) molecules in tumors from patients with hepatocellular carcinoma (HCC). Monocytes activated by tumors strongly express PD-L1 proteins with kinetics similar to their activation status, and significant correlations were found between the levels of PD-L1(+) and HLA-DR(high) on tumor-infiltrating monocytes. Autocrine tumor necrosis factor alpha and interleukin 10 released from activated monocytes stimulated monocyte expression of PD-L1. The PD-L1(+) monocytes effectively suppressed tumor-specific T cell immunity and contributed to the growth of human tumors in vivo; the effect could be reversed by blocking PD-L1 on those monocytes. Moreover, we found that PD-L1 expression on tumor-infiltrating monocytes increased with disease progression, and the intensity of the protein was associated with high mortality and reduced survival in the HCC patients. Thus, expression of PD-L1 on activated monocytes/Mphi may represent a novel mechanism that links the proinflammatory response to immune tolerance in the tumor milieu.
Despite the fact that CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg cells) play a central role in maintaining self-tolerance and that IL-17-producing CD4(+) T cells (Th17 cells) are pathogenic in ...many autoimmune diseases, evidence to date has indicated that Th17 cells are resistant to suppression by human Foxp3(+) Treg cells. It was recently demonstrated that CD39, an ectonucleotidase which hydrolyzes ATP, is expressed on a subset of human natural Treg cells. We found that although both CD4(+)CD25(high)CD39(+) and CD4(+)CD25(high)CD39(-) T cells suppressed proliferation and IFN-gamma production by responder T cells, only the CD4(+)CD25(high)CD39(+), which were predominantly FoxP3(+), suppressed IL-17 production, whereas CD4(+)CD25(high)CD39(-) T cells produced IL-17. An examination of T cells from multiple sclerosis patients revealed a normal frequency of CD4(+)CD25(+)CD127(low)FoxP3(+), but interestingly a deficit in the relative frequency and the suppressive function of CD4(+)CD25(+)CD127(low)FoxP3(+)CD39(+) Treg cells. The mechanism of suppression by CD39(+) Treg cells appears to require cell contact and can be duplicated by adenosine, which is produced from ATP by the ectonucleotidases CD39 and CD73. Our findings suggest that CD4(+)CD25(+)Foxp3(+)CD39(+) Treg cells play an important role in constraining pathogenic Th17 cells and their reduction in multiple sclerosis patients might lead to an inability to control IL-17 mediated autoimmune inflammation.
Selecting rice varieties that adsorb less or more Cd from soil can be respectively applied to safety rice production and phytoremediation. Considering plant-induced Cd mobilization will contribute to ...the rice cultivar screening. We firstly executed a pot experiment to assess the effect of rice plants on soil Cd forms (BCR method). The results showed that the presence of rice significantly reduced residual-Cd (BCR4) concentrations, indicating the rice plant-induced insoluble Cd mobilization. Subsequent sand culture trial with four rice species (conventional and hybrid low-Cd rice, conventional and hybrid high-Cd rice) and four insoluble Cd compounds (CdS, Cd3(PO3)2, CdCO3 and CdSe) were conducted to further discuss the interaction between insoluble Cd among different rice varieties. The results showed that rice plants do solubilize soil Cd especially insoluble Cd form due to the interaction among rhizosphere acidification, root secretion of organic matter ligand and other ligands, like phytosiderophore. High-Cd cultivar and hybrid rice cultivar had a greater ability to solubilize the insoluble Cd. Visual MINTEQ predicted that free Cd2+ (∼85.6%) were the dominant Cd speciation of mobilized Cd followed by Cd-DOM complexes (∼7.80%) and other ligand-complexes (∼6.51%) in the rhizosphere solution. Cd bound to protein and pectates and to undissolved phosphate were the major mobilized-Cd chemical forms in rice roots and shoots. In addition, the subcellular analysis suggested that half of mobilized-Cd precipitated in the cell wall of rice root and shoot and the other Cd entranced into the protoplast of rice cell. The fate of rice plant-induced insoluble Cd mobilization could be an indispensable factor in prospective phytoremediation and cleaner rice production.
Display omitted
Rice consumption is one of the major cadmium (Cd) exposure routes for human. Bangladeshi people have historically subsisted on a rice-based diet; however, only a few reports have investigated Cd ...accumulation by different rice cultivars in Bangladesh. This study was designed to investigate the uptake and accumulation of Cd in different rice cultivars and associated health risks to humans eating rice. A pot experiment was conducted to grow eight amon rice varieties under control, 5 and 10 mg Cd/kg soil under open air conditions. After harvesting the Cd fractionation, bioavailable Cd and rice grain Cd content were determined. Cd spiked as Cd
2+
enriched the Cd bioavailability to plant by 35% (in 5 mg/kg stress) and 85% (in 10 mg/kg stress). There were variations among the rice varieties in their ability to accumulate Cd in grain and this was found to be 15-fold higher under control conditions. Grain Cd content significantly differed among the rice varieties at each level of soil Cd. In this study, BR-52 emerged as the most Cd-safe cultivar followed by BR-75, Rani salut, BR-71, BR-49, BR-76, BR-87 and lastly, BINA-7. Most of the agronomic parameters of rice concerning yield were affected by both rice varieties and soil Cd level. In different rice varieties, rhizosphere pH increased through root exudation which ultimately produced equilibria among the five major soil Cd fractions so that Cd became bioavailable to plants. All rice varieties showed high hazard quotient (HQ) values under Cd stress conditions and posed a risk to human health. For noncarcinogenic health risk assessment through HQ, we recommend 0.1 mg Cd/kg rice grain be used as the maximum allowable concentration (MAC) in calculating health risk for Bangladeshi people.
•Long-term rice straw removal reduced the total concentrations of Cd in soil.•Atmospheric deposition led to lower remediation efficiency of Cd by straw removal.•Long-term rice straw return obviously ...increased the bioavailability of Cd in soil.•Cd accumulation in late rice tissues was higher than early rice under straw return.
Several studies have demonstrated that reintroducing crop straw to fields may intensify cadmium (Cd) contamination in agricultural soils. However, the specific effects of long-term straw management practices on Cd concentration and its bioavailability in soil-rice ecosystems remain unclear. In this context, to explore the influence of straw return (SR) and straw removal (NSR) on Cd accumulation in both soil and rice within a double-cropping system, we conducted a four-year field study. Our research study unveiled that NSR consistently decreased soil Cd concentration and its bioavailability by approximately 16.93%–27.30% and 8.23%–21.05% respectively across both study sites. Conversely, SR resulted in a substantial increase in soil Cd bioavailability, ranging from 38.64%–53.95%. Notably, compared to NSR, SR significantly increased total soil Cd by 5.47%–36.58% and increased Cd content in brown rice by 8.00%–100.24%. Remarkably, after four consecutive years of NSR, brown rice Cd concentration at the Changfeng site compiled with national safety standards (GB 2762–2022). Additionally, returning early rice straw significantly raised soil Cd bioavailability for the subsequent crop, more so than late rice straw did for the early rice the following year. The findings suggest that traditional double-cropping cultivation with straw removal can effectively mitigate Cd contamination risks in crops and farmland in Hunan Province.
Display omitted
The reaction of Cd(OAc)2·2H2O with less nucleophilic and less basic 3,5-lutidine (pKa=6.15) in methanol at ambient temperature affords a linear one-dimensional coordination polymer (1D CP) 3, while ...the analogous reaction carried out with more nucleophilic and more basic 3,4-lutidine (pKa=6.46) affords a syndiotactic 1D CP 4. Display omitted
The reactions of Cd(OAc)2·2H2O with variously substituted pyridines in methanol afforded unique one-dimensional coordination polymers (1D CPs), Cd2(μ2-κ2:κ1-OAc)2(μ2-κ1:κ1-OAc)2L2 (L=NC5H5 (1), NC5H4Me-3 (2), and NC5H3Me2-3,5 (3)) and Cd3(μ3-κ1:κ2-OAc)3(μ2-κ2-OAc)(μ2-κ2:κ1-OAc)2(NC5H3Me2-3,4)2 (4), and discrete and bimolecular complexes, (Cd(OAc)2(NC5H3Me2-3,4)2(H2O)2 (5), Cd(κ2-OAc)2(NC5H4Me-4)2(H2O)·Cd(κ2-OAc)2(H2O)2) (6), Cd(κ2-OAc)2L2L′·xH2O (x=0, L′=H2O, L=NC5H4(OMe)-4 (7); NC5H4tBu-4 (8); x=2, L=L′=NC5H4(NMe2)-4 (9·2H2O)). The products were characterised by elemental analysis, IR, solution NMR (1H and 13C), solid-state CP-MAS 13C{1H} and 113Cd NMR, TGA/DTA analyses, and single crystal X-ray diffraction. Phase purity of 1–4 was verified by powder X-ray diffraction (PXRD). Plausible mechanisms of formation of the products are proposed based on a point zero charge model. 4 represents the first cadmium containing 1D CP that possesses a tridentate bridging (μ3-κ1:κ2) acetate coordination mode and 6 represents the first structurally characterised bimolecular cadmium(II) complex containing two different neutral cadmium(II) coordination species per formula unit. 9·2H2O was calcined at 500°C to afford CdO as confirmed by PXRD and the morphology of CdO was studied by scanning electron microscopy.
Endosialin/TEM1 was originally discovered as a human embryonic fibroblast-specific antigen and was later found to be differentially expressed in tumor stroma and endothelium. Endosialin/TEM1 ...over-expression has been observed in many cancers of various tissue origin, including colon, breast, pancreatic, and lung. The knockout (KO) mouse model showed the absence of endosialin/TEM1 expression reduced growth, invasion, and metastasis of human tumor xenografts. In addition, lack of endosialin/TEM1 led to an increase in small immature blood vessels and decreased numbers of medium and large tumor vessels. This abnormal angiogenic response could be responsible for the reduced tumor growth and invasion observed in endosialin/TEM1 KO mice, suggesting a role for endosialin/TEM1 in controlling the interaction among tumor cells, endothelia, and stromal matrix. Here we report the identification of fibronectin (FN) and collagen types I and IV as specific ligands for endosialin/TEM1. More importantly, cells expressing endosialin/TEM1 exhibit enhanced adhesion to FN as well as enhanced migration through matrigel, although these properties could be blocked by a humanized antibody directed against human endosialin/TEM1. Our results pinpoint to a molecular mechanism by which expression of endosialin/TEM1 in the tumor stroma and endothelium may support tumor progression and invasion.
The immunoproteasome plays a key role in generation of HLA peptides for T cell-mediated immunity. Integrative genomic and proteomic analysis of non-small cell lung carcinoma (NSCLC) cell lines ...revealed significantly reduced expression of immunoproteasome components and their regulators associated with epithelial to mesenchymal transition. Low expression of immunoproteasome subunits in early stage NSCLC patients was associated with recurrence and metastasis. Depleted repertoire of HLA class I-bound peptides in mesenchymal cells deficient in immunoproteasome components was restored with either IFNγ or 5-aza-2′-deoxycytidine (5-aza-dC) treatment. Our findings point to a mechanism of immune evasion of cells with a mesenchymal phenotype and suggest a strategy to overcome immune evasion through induction of the immunoproteasome to increase the cellular repertoire of HLA class I-bound peptides.
PDF
