Effects of the Aidi Dripping Pills on Immune Functions of the Tumor-bearing Mouse

ObjectiveTo study the effects of Aidi Dripping Pills on immune functions of the tumor-bearing mouse on the basis of the previous experimental studies on its tumor-inhibiting and life-prolonging effects.MethodsBy using the transplantation tumor mouse models, the effects of Aidi Dripping Pills on the lymphocyte transformation rate and the hemolysin formation in the S180 tumor-bearing mice, and on the phagocytic function of macrophages in the abdominal cavity of H22 tumor-bearing mice were investigated.ResultsIn the 2.25 g/kg and 1.125 g/kg Aidi Dripping Pills groups, the lymphocyte transformation rates in the S180 tumor-bearing mice were significantly higher than that of the control group (P<0.01). In all the Aidi Dripping Pills groups, HC50 significantly increased (P<0.01 or P<0.05), carbon granular clearance significantly raised, and both the phagocytic index and phagocytic coefficient were significantly higher than those in the control group (P<0.01 or P<0.05).ConclusionThe Aidi Dripping Pills can significantly increase the cellular immune function, the humoral immune function and the phagocytic function of the mononuclear-macrophages, so it may show anti-tumor effects by enhancing the function of the reticuloendothelial system

Inactivation of the MDM2 RING domain enhances p53 transcriptional activity in mice

The MDM2 RING domain harbors E3 ubiquitin ligase activity critical for regulating the degradation of tumor suppressor p53, which controls many cellular pathways. The MDM2 RING domain also is required for an interaction with MDMX. Mice containing a substitution in the MDM2 RING domain, MDM2C462A, disrupting MDM2 E3 function and the MDMX interaction, die during early embryogenesis that can be rescued by p53 deletion. To investigate whether MDM2C462A, which retains p53 binding, has p53-suppressing activity, we generated Mdm2C462A/C462A;p53ER/- mice, in which we replaced the endogenous p53 alleles with an inducible p53ER/- allele, and compared survival with that of similarly generated Mdm2-/-;p53ER/- mice. Adult Mdm2-null mice died ~7 days after tamoxifen-induced p53 activation, indicating that in the absence of MDM2, MDMX cannot suppress p53. Surprisingly, Mdm2C462A/C462A;p53ER/- mice died ~5 days after tamoxifen injection, suggesting that p53 activity is higher in the presence of MDM2C462A than in the absence of MDM2. Indeed, in MDM2C462A-expressing mouse tissues and embryonic fibroblasts, p53 exhibited higher transcriptional activity than in those expressing no MDM2 or no MDM2 and MDMX. This observation indicated that MDM2C462A not only is unable to suppress p53 but may have gained the ability to enhance p53 activity. We also found that p53 acetylation, a measure of p53 transcriptional activity, was higher in the presence of MDM2C462A than in the absence of MDM2. These results reveal an unexpected role of MDM2C462A in enhancing p53 activity and suggest the possibility that compounds targeting MDM2 RING domain function could produce even more robust p53 activation

Donor Bone Marrow-Derived T Cells Inhibit GVHD Induced by Donor Lymphocyte Infusion in Established Mixed Allogeneic Hematopoietic Chimeras

Delayed administration of donor lymphocyte infusion (DLI) to established mixed chimeras has been shown to achieve anti-tumor responses without graft-vs.-host disease (GVHD). Herein we show that de novo donor BM-derived T cells that are tolerant of the recipients are important in preventing GVHD in mixed chimeras receiving delayed DLI. Mixed chimeras lacking donor BM-derived T cells developed significantly more severe GVHD than those with donor BM-derived T cells after DLI, even though both groups had comparable levels of total T cells at the time of DLI. Post-DLI depletion of donor BM-derived T cells in mixed chimeras, as late as 20 days after DLI, also provoked severe GVHD. Although both CD4 and CD8 T cells contributed to the protection, the latter were significantly more effective, suggesting that inhibition of GVHD was not mainly mediated by CD4 regulatory T cells. The lack of donor BM-derived T cells was associated with markedly increased accumulation of DLI-derived alloreactive T cells in parenchymal GVHD target tissues. Thus, donor BM-derived T cells are an important factor in determining the risk of GVHD and therefore, offer a potential therapeutic target for preventing and ameliorating GVHD in the setting of delayed DLI in established mixed chimeras

MiR-20a regulates the PRKG1 gene by targeting its coding region in pulmonary arterial smooth muscle cells

AbstractChronic hypoxia triggers pulmonary vascular remodeling, which is associated with de-differentiation of pulmonary artery smooth muscle cells (PASMC). Here, we show that miR-20a expression is up-regulated in response to hypoxia in both mouse and human PASMC. We also observed that miR-20a represses the protein kinase, cGMP-dependent, type I (PRKG1) gene and we identified two crucial miR-20a binding sites within the coding region of PRKG1. Functional studies showed that miR-20a promotes the proliferation and migration of human PASMC, whereas it inhibits their differentiation. In summary, we provided a possible mechanism by which hypoxia results in decreased PRKG1 expression and in the phenotypic switching of PASMC

Superconducting Zirconium Polyhydrides at Moderate Pressures.

Highly compressed hydrides have been at the forefront of the search for high-Tc superconductivity. The recent discovery of record-high Tc's in H3S and LaH10±x under high pressure fuels the enthusiasm for finding good superconductors in similar hydride groups. Guided by first-principles structure prediction, we successfully synthesized ZrH3 and Zr4H15 at modest pressures (30-50 GPa) in diamond anvil cells by two different reaction routes: ZrH2 + H2 at room temperature and Zr + H2 at ∼1500 K by laser heating. From the synchrotron X-ray diffraction patterns, ZrH3 is found to have a Pm3̅n structure corresponding to the familiar A15 structure, and Zr4H15 has an I4̅3d structure isostructural to Th4H15. Electrical resistance measurement and the dependence of Tc on the applied magnetic field of the sample showed the emergence of two superconducting transitions at 6.4 and 4.0 K at 40 GPa, which correspond to the two Tc's for ZrH3 and Zr4H15.This work was supported by the National Key R&D Program of China (No. 2018YFA0305900), National Natural Science Foundation of China (Nos. 51632002, 11674122, 51572108, and 11504127), Program for Changjiang Scholars and Innovative Research Team in University (No. IRT_15R23), the 111 Project (No. B12011), and the Natural Sciences and Engineering Research Council of Canada (NSERC). C.J.P. acknowledges financial support from the Engineering and Physical Sciences Research Council (Grant EP/P022596/1) and a Royal Society Wolfson Research Merit award

Polyhydride CeH9 with an atomic-like hydrogen clathrate structure.

Compression of hydrogen-rich hydrides has been proposed as an alternative way to attain the atomic metallic hydrogen state or high-temperature superconductors. However, it remains a challenge to get access to these states by synthesizing novel polyhydrides with unusually high hydrogen-to-metal ratios. Here we synthesize a series of cerium (Ce) polyhydrides by a direct reaction of Ce and H2 at high pressures. We discover that cerium polyhydride CeH9, formed above 100 GPa, presents a three-dimensional hydrogen network composed of clathrate H29 cages. The electron localization function together with band structure calculations elucidate the weak electron localization between H-H atoms and confirm its metallic character. By means of Ce atom doping, metallic hydrogen structure can be realized via the existence of CeH9. Particularly, Ce atoms play a positive role to stabilize the sublattice of hydrogen cages similar to the recently discovered near-room-temperature lanthanum hydride superconductors

The Systemic Evaluation and Clinical Significance of Immunological Function for Advanced Lung Cancer Patients

Background and objective The actual evaluation of immunological function is significant for studing the tumor development and devising a treatment in time. The aim of this study is to evaluate the immunological function of advanced lung cancer patients systematically, and to discuss the clinical significance. Methods The nucleated cell amounts of advanced lung cancer patients and the healthy individuals were counted. The immune cell subsets and the levels of IL-4, INF-γ, perforin and granzyme in CD8+T cells by the flow cytometry were measured. The proliferation activity and the inhibition ratio of immune cells to several tumor cell lines were evaluated by MTT assay. Results The absolute amounts and subsets of T, B, NK cells of advanced lung cancer patients were lower than the healthy individuals (P < 0.05); However, the proportion of regulatory T cells of advanced lung cancer patients (4.00±1.84)% was lower than the healthy individuals (1.27±0.78)% (P < 0.05). The positive rates of IFN-γ perforin, granzyme in CD8+T cells decreased while them in IL-4 did not in the advanced lung cancer patients compared to the healthy control group (P < 0.05). The proliferation activity of immune cells, the positive rate of PPD masculine and the inhibition ratio to tumor cells in the advanced lung cancer patients was lower than the healthy subsets obviously (P < 0.05). Conclusion There was a significant immune depression in the advanced lung cancer patients compared to the healthy individuals

Extracellular Proteome Analysis and Flavor Formation During Soy Sauce Fermentation

Aspergillus oryzae is an excellent strain for soy sauce fermentation because of its complicated enzyme system, especially protease. The aim of this study was to investigate the key enzymes and flavors during soy sauce fermentation, and a comparative assessment of extracellular enzymes during various fermentation stages at the proteomic level via iTRAQ analysis is presented. Many important enzymes related to the amino acid and glucose metabolisms participated in the material decomposition under high-salt stress. Dipeptidase, dipeptidyl aminopeptidase, leucine aminopeptidase, aspartic protease pep1, and extracellular metalloproteinase played positive roles during the early stage of soybean mash fermentation, whilst leucine aminopeptidase A and extracellular metalloproteinase NpI were the dominant proteolytic enzymes during the later period of fermentation. At the same time, β-glucosidase and β-xylanase exerted great effects upon glucose metabolism throughout the fermentation process. The results show that protease and amylolytic enzymes are complementary in the formation of flavors such as alcohols, acids, esters, aldehydes, furans, and pyrazines during soy sauce fermentation

Novel HLA-DRB1 alleles contribute risk for disease susceptibility in primary biliary cholangitis

Background: Primary biliary cholangitis (PBC) is a complex disease with high heritability. We investigated the association between human leukocyte antigen (HLA)-DRB1 alleles and PBC in families and sporadic cases to evaluate the genetic components of the disease. Methods: We performed whole exome sequencing in three PBC families. We genotyped HLA-DRB1 and calculated the association between HLA-DRB1 alleles and the encoding amino acid sequences with the clinical features. Results: Ten variants harboured the HLA-DRB1 gene associated with PBC. DRB1 x07:01, 14:01 and 14:05 were highly increased in PBC. Ten coding region polymorphisms were associated with PBC that encode the amino acid variants of HLA-DR beta 54, beta 59 and beta 66 located in the peptide-binding site of the MHC molecule. Glutamine at position 54 was confirmed as a risk amino acid, verifying the results of familial aggregation analysis of PBC families. Discussion: Familial aggregation analysis indicated that HLA-DRB1 is a candidate gene for the risk of disease course. Considering that amino acid variations are critical to peptide-binding properties, they underlie the major component of MHC association with PBC. (c) 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved