acupoint-plaster-application-combined-with-omalizumab-for-severe

Acupoint Plaster Application Combined with Omalizumab for Severe Allergic Asthma: A Randomized Controlled Trial

Some patients with severe allergic asthma remain poorly controlled despite guideline&#8209;recommended therapy. This prospective randomized controlled ...

Graduate School of Chengdu University of Traditional Chinese Medicine

Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.

Deubiquitination and Stabilization of PD-L1 by CSN5.

Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Although histologically defined by the presence of malignant osteoid, the tumor possesses lineage multipotency suggesting it could be derived from a cell anywhere on the differentiation pathway between a mesenchymal stem cell (MSC) and a mature osteoblast. To determine if preosteoblasts (pOB) could be the cell of origin differentiated MSCs were transformed with defined genetic elements. MSCs and pOB differentiated from the same MSCs were serially transformed with the oncogenes hTERT, SV40 large T antigen and H-Ras. Assays were performed to determine their tumorigenic properties, differentiation capacity and histologic appearance. When subcutaneously implanted in immunocompromised mice, cell lines derived from transformed MSC and pOB formed tumors in 4 weeks. In contrast to the transformed MSC, the pOB tumors demonstrated a histological appearance characteristic of osteosarcoma. The cell lines derived from the transformed pOB only had osteogenic and chondrogenic differentiation potential, but not adipogenic ones. However, the transformed MSC cells and standard osteosarcoma cell lines maintained their tri-lineage differentiation capacity. The inability of the transformed pOB cell line to undergo adipogenic differentiation, may suggest that osteosarcoma is derived from a cell intermediate in differentiation between an MSC and a pOB, with partial commitment to the osteoblastic lineage.

Genetically transforming human osteoblasts to sarcoma: development of an osteosarcoma model.

The metabolic syndrome and diabetic conditions support atherosclerosis, but the exact mechanisms for accelerated atherogenesis remain unclear. Although the proinflammatory role of STAT4 in atherosclerosis and diet-induced insulin resistance (IR) was recently established, the impact of STAT4 on atherogenesis in conditions of IR is not known. In this study, we generated Stat4(-/-)Ldlr(-/-) mice that were fed a diabetogenic diet with added cholesterol (DDC). DDC-fed Stat4(-/-)Ldlr(-/-) mice demonstrated improved glucose tolerance, insulin sensitivity, and a 36% reduction in atherosclerosis compared with Ldlr(-/-) controls. Interestingly, we detected a reduction in T follicular helper (Tfh) cells and plasma B cells but a sharp elevation in CD8(+) regulatory T cells (Tregs) in spleens and aortas of Stat4(-/-)Ldlr(-/-) mice compared with Ldlr(-/-) mice. Similarly, STAT4 deficiency supported CD8(+) Treg differentiation in vitro. STAT4-deficient CD8(+) Tregs suppressed Tfh cell and germinal center B cell development upon immunization with keyhole limpet hemocyanin, indicating an important role for STAT4 in CD8(+) Treg functions in vivo. Furthermore, adoptive transfer of Stat4(-/-)Ldlr(-/-) CD8(+) Tregs versus Ldlr(-/-) CD8(+) Tregs resulted in a significant reduction in plaque burden and suppression of Tfh cell and germinal center B cells in DDC-fed Ldlr(-/-) recipients. STAT4 expression in macrophages (MΦs) also affected the Tfh/CD8(+) Treg axis, because conditioned media from Stat4(-/-)Ldlr(-/-) MΦs supported CD8(+) Treg differentiation, but not Tfh cell differentiation, in a TGF-β-dependent manner. These findings suggest a novel mechanism by which STAT4 supports atherosclerosis in IR Ldlr(-/-) mice via STAT4-dependent MΦs, as well as cell-intrinsic suppression of CD8(+) Treg generation and functions and maintenance of Tfh cell generation and the accompanying humoral immune response.

Article	Year
Deubiquitination and Stabilization of PD-L1 by CSN5. Cancer cell\| PubMed ID: 27866850	2016
Genetically transforming human osteoblasts to sarcoma: development of an osteosarcoma model. Genes & cancer\| PubMed ID: 28435520	2017
STAT4 Regulates the CD8(+) Regulatory T Cell/T Follicular Helper Cell Axis and Promotes Atherogenesis in Insulin-Resistant Ldlr(-/-) Mice. Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 29055004	2017

Yi Yang

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