bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resveratrol-dependent sensitization of prostate cancer cells (165.33)
Authors: Mishra Manoj , Eroglu Erdal , Singh Udai , Singh Shree 
Published: January 2023

Abstract
Prostate Cancer (PCa) is the most common non-skin malignancy and commonly diagnosed cancer, and second most cancer responsible for death in men in United States. Prior studies in animal models of PCa as well as in human, demonstrated that the prostate produces several growth factors. Addition or blocking of these growth factors can alter the PCa cell proliferation and other important functions. Resveratrol (RES), a polyphenolic compound found in the skin of red fruits, exhibits anti-inflammatory, anti-oxidative, anti-cancer, and anti-proliferative characteristics. In this study, the role RES has been investigated on mouse prostate cancer (PCa) cell lines, derived from transgenic adenocarcinoma of mouse prostate (TRAMP), in C57/B6 mice. Interestingly, TRAMP-C1 and TRAMP-C2 form tumors while TRAMP-C3 fails to form tumors. TRAMP cells were treated with different concentration of resveratrol and at different time points analyzed for intensity of sensitization, cytokines, growth factors as well as apoptotic genes. The results show that TRAMP C1 and C2 were resistant to RES compared to TRAMP C3 suggesting that TRAMP-C3 cells may up regulate “kill me signal” that help in sensitization of these cells compared to TRAMP C1 and C2. This data also demonstrates that RES mode of action is specific for each cell line in activating program cell death that may utilize unique sets of genes during apoptotic pathways.
Tumor growth is attenuated in eosinophil-deficient mouse models (165.41)
Authors: Jacobsen Elizabeth , Taranova Anna , Ochkur Sergei , Protheroe Cheryl , Condjella Rachel , Colbert Dana , Zellner Katie , McGarry Michael , Lee James , Lee Nancy 
Published: January 2023

Abstract
Eosinophil infiltration into tumors has been associated with positive and negative growth human cancers and in mouse models of tumorigenesis. Our previous studies have shown that eosinophils infiltrate tumors and differentially accumulate in the necrotic and capsule regions of tumors. Using various eosinophil-deficient mouse models, we demonstrate that in the absence of eosinophils tumor growth is attenuated. Methods: Tumor growth kinetics were assessed using a B16F10 melanoma subcutaneous cell injection model. Eosinophil chemotaxis was assessed using an ex vivo transwell insert assay system. We compared tumor growth in wild type animals vs. various eosinophil-deficient mouse models that are transgenic line of mice (PHIL) and MBP-/-/EPO-/- double knockout mice that are deficient in eosinophil-specific proteins (major basic protein (MBP) and eosinophil peroxide (EPO)) resulting in a blockade of eosinophilpoiesis. Conclusions: The migration of eosinophils was inhibited through blocking the sphingosine-1-phosphate pathway, suggesting recruitment and accumulation is primarily an inflammatory response. Tumor growth was decreased by ~40-60% in PHIL and in MBP-/-/EPO-/- double knockout mice relative to tumors in wild type animals. In addition, EPO-/- mice, and not MBP-/-mice, replicate this ~40% reduction in tumor size implicating a significant role for EPO in tumor growth kinetics. These data suggest eosinophils respond to inflammatory mediators and mediate augment tumor growth.
Live-imaging of antigen presenting cells in spontaneous breast cancer (165.44)
Authors: Engelhardt John , Krummel Matthew 
Published: January 2023

Abstract
The immune response to tumors is thought to be inactivated, but the subsets of cells that ingest tumor to present to incoming immune cells have remained enigmatic. We generated a genetically encoded fluorescent mouse model of breast cancer to track antigen flow from tumors into immune cells, and defined a subset of tumorAPC (tAPC) that ingest tumor debris in the steady-state, act as a major repository of tumor-derived antigens, and present these antigens to tumor-reactive T cells. Using intravital live-imaging we show that this population represents a unique spatial subset of slow-moving marginating myeloid cells that interact closely with the tumor margin. We further show that these cells nucleate clusters of tumor-specific T cells, but appear to ‘anergize’ them. This study highlights a major route of immunosuppression in the tumor microenvironment and suggests immunotherapies based on modulating the function of tAPC.
Activation of p53 and NF-kB degradation by SOCS1 to promote cancer cell apoptosis and to suppress implanted tumor growth (165.47)
Authors: Lee Choong-Eun 
Published: January 2023

Abstract
The suppressors of cytokine signaling (SOCS), play multiple roles in cell survival, differentiation and apoptosis in diverse cell systems. We have investigated mechanisms of tumor-suppressive functions of SOCS using HCT116 colon cancer cells (HCT116:p53wt and HCT116:p53-/-) by employing over-expression or knock-down of SOCS isoforms. Our data show that SOCS1 but not SOCS3 promoted γ-irradiation-induced apoptosis by up-regulating p53 activation and Bax expression. SOCS1 also modulated cell cycle arrest induced by γ-irradiation resulting in increase in G1 arrest which was associated with up-regulation of p21. In addition, SOCS1 suppressed the radiation-induced survival pathway including Erk, NF-kB and Bcl2 expression. The modulatory effects of SOCS1 on cell cycle changes correlated well with the negative regulation of Jak3/STAT3 and Erk activation, and the transfection of siSTAT3 as well as treatment of inhibitors of Jaks and Erk induced effects similar to SOCS1 over-expression. In addition, the SOCS1-mediated NF-kB degradation appears important in counteracting the survival response triggered upon apoptoptic stimuli. Furthermore, SOCS1-transfected HCT116/SOCS1 tumor cells implanted in nude mice exhibited reduced tumor sizes as compared to HCT116/mock cells upon γ-irradiation. The results indicate the promotion of radiosensitivity by SOCS1, which may be useful for the development of a therapeutic regimen to overcome radioresistance often found in certain colorectal cancers.
Hypoxia inducible factor-α expression correlates with thymosin β4 overexpression related to lymph node metastasis in breast cancer (165.5)
Authors: Yoon Sun Young , Kim Joo Heon , Cho Daeho 
Published: January 2023

Abstract
Two hypoxia inducible factors (HIFs), HIF-1α and HIF-2α, are induced by hypoxia, and high expression of these proteins is correlated with angiogenesis and distant metastasis. Thymosin β4 (Tβ4) is frequently highly expressed in cancer, and this over-expression correlates with malignant progression. The objective of this study was to investigate the clinical correlation of HIF-α with Tβ4 and the intracellular functional roles of Tβ4 on HIF-α activation. We showed that high expression levels of HIF-1α and HIF-2α strongly correlated with Tβ4 expression (P&lt;0.0001), and over-expression of Tβ4 correlated significantly with lymph node metastasis (P&lt;0.05) in patients with breast cancer. Additionally, we demonstrated that hypoxia up-regulates intracellular Tβ4 protein, which then affects HIF-α activity, which is a key in regulating vascular epidermal growth factor (VEGF) expression. We confirmed that hypoxia-induced intracellular Tβ4 and HIF-α activity were reduced by inhibiting Tβ4 expression using Tβ4 shRNA lentivirus. VEGF-A was also down regulated, but VEGF-C and VEGF-D expressions were not affected. These findings suggest that over-expression of Tβ4 is strongly associated with HIF-1α and HIF-2α expression and is also clinicopathologically involved in lymph node metastatic potential of breast cancer through the modulation of HIF-α activation and induction of VEGF-A. Ultimately, these results highlight Tβ4 as a potentially therapeutic target in malignant cancers.
Neural stem/progenitor cells are targets for natural killer cell-mediated killing (169.40)
Authors: Phillips Lori , Gould Elizabeth , Palmer Theo , Krams Sheri , Martinez Olivia 
Published: January 2023

Abstract
Neural Progenitor Cells (NPC) are multipotent progenitors that can differentiate into neurons. NPC in the hippocampus undergo neurogenesis throughout adult life, but the regenerative capacity of this endogenous pool appears inadequate in a variety of CNS diseases. Transplantation of NPC may repopulate or repair damaged areas of the CNS, however, the immune response to NPC allografts is not well characterized. Primary murine NPC display low levels of MHC class I and no class II as determined by flow cytometry. NPC also express intermediate levels of RAE-1, a ligand for the NK cell activation receptor NKG2D. Primary NK cells isolated from BALB/c (H-2d) or C57BL/6 (H-2b) mice can lyse both syngeneic and allogeneic NPC. NK cell killing is significantly inhibited when MHC class I is upregulated on syngeneic NPC targets following IFN-γ exposure (64% and 47% less killing by BALB/c and C57BL/6 NK cell effectors, respectively.) Additionally, NKG2D-/- NK cell effectors are significantly diminished in their ability to target NPC (56% and 68% less killing for matched and mismatched targets, respectively.) This indicates that MHC class I and the NKG2D ligand, RAE-1, play critical roles in NK cell recognition of NPC and suggests that host NK cells that traffic to the NPC graft site after transplantation can recognize and kill transplanted NPC. Thus, strategies to deplete NK cells or decrease NKG2D ligand expression on NPC grafts may lead to improved graft survival and differentiation.
CD11cHI macrophages are specialized APCs in the early human placenta (169.45)
Authors: Houser Brandy , Guerin Leigh , Wu Vernon , DeJong Annemiek , Moody D. Branch , Strominger Jack 
Published: January 2023

Abstract
The human maternal-fetal interface is a unique environment by which there is a necessary establishment of maternal tolerance to fetal antigens as well as uterine spiral artery remodeling and placental growth. Decidual macrophages (dMΦs) comprise approximately 20% of all leukocytes at this interface. Previously we identified two distinct populations based upon CD11c and have been termed, CD11cHI and CD11cLO MΦs (J Immunol. 2011; 186(4)). Based upon microarray analysis, CD11cHI and CD11cLO dMΦs were shown to have significantly divergent functions. Using a DQ-BSA assay we demonstrate that CD11cHI cells process exogenous protein antigens efficiently while processing by CD11cLO cells is very low. Furthermore, several CD1 molecules are expressed on the surface of CD11cHI dMΦs including CD1a, CD1c and CD1d. CD1 molecules are non-polymorphic glycolipid-presenting molecules that have no known function at the maternal-fetal interface. In order to determine functional relevance, we utilized established CD1-specific T cell clones and known ligands for CD1a and CD1c [CD8.2, dideoxymycobactin (DDM); CD8.1, mannosyl-β1-phosphomycoketide (MPM)] respectively. CD11cHI dMΦs, but not CD11cLO dMΦs, were found to specifically stimulate these T cell clones. Thus, these data suggest that the CD11cHI dMΦs may function in two different antigen-presenting systems at the maternal-fetal interface during early human pregnancy, peptide presentation and glycolipid presentation.
Lack of CD4 help induces tolerance of CD8 T cell response for H60, a dominant minor histocompatibility antigen. (169.46)
Authors: Ryu Su Jeong , Jung Kyung Min , Choi Eun Young 
Published: January 2023

Abstract
Mismatch on minor histocompatibility (H) antigens is a major obstacle for the success of transplantation between MHC-matched individuals, generating CD4 and CD8 T cell responses specific for the disparate allo-minor H antigens. H60 is a dominant minor H antigen, for which specific CD8 T cell response dominates over those for other minor H antigens in B6 anti-BALB.B response. In our previous study, the H60-specific CD8 T cell response was found to be Th dependent, requiring CD4 T cell activation for both the primary and memory expansion. Here, we show that CD4 help deficiency during the induction of the H60-specific CD8 T cell response not only forbids the primary blast expansion but also prevents the specific memory response development, implying the tolerance induction of the H60 specific CD8 T cells under helpless condition. H60-specific CD8 T cells activated under the helpless condition were more prone to cell death than those under helped condition. Tolerance induction on the H60-specific CD8 T cells rendered the total CD8 T cell immunity of B6 mice to BALB.B to be diminished, while it remained unaffected by matching on H60. The results demonstrate that CD4 help provision influences CD8 immunity against minor H antigens and suggest that tolerance of CD8 T cell response to dominant antigen would be applicable for controlling transplantation rejection or GVHD.
Characterization of adaptive immune receptors in hagfish (170.13)
Authors: Guo Peng , Gartland Lanier , Li Jianxu , Hirano Masayuki , Alder Matthew , Herrin Brantley , Sides Jeffrey , Kasahara Masanori , Cooper Max 
Published: January 2023

Abstract
Instead of the immunoglobulin based antigen receptors of jawed vertebrates, jawless fish use variable lymphocyte receptors (VLRs) comprised of leucine-rich-repeat (LRR) segments for antigen recognition. Two VLR genes, VLRA and VLRB, have been identified in both lampreys and hagfish. A third VLR, so called VLRC was recently discovered in lampreys. An extensive VLR repertoire is generated through the insertion of diverse LRR sequences into an incomplete germline VLR gene by a gene conversion mechanism. Earlier studies of sea lampreys have shown that VLRB lymphocytes resemble B cells of jawed vertebrates, whereas VLRA lymphocytes are similar to T cells. For the present studies, monoclonal and polyclonal antibodies against the invariant stalk regions of hagfish VLRA and VLRB were produced to identify the VLR-bearing lymphocytes and their products. Flow cytometric analysis indicated that VLRA and VLRB are expressed by separate lymphocyte populations, with VLRA lymphocytes being the dominant population. Western blot and gel-filtration analyses indicated that hagfish VLRB antibodies are released into the circulation as multimeric proteins that are formed by non-covalent linkage of four or five disulfide-bonded VLRB dimers. Conversely, soluble VLRA is not detected in hagfish plasma. These findings indicate that distinctive T-like and B-like lineages are a common feature of the adaptive immune system in both lampreys and hagfish, in keeping with their monophyletic relationship.
Response gene to complement 32 mediate TGF-beta induced production of extracellular matrix by astrocytes (44.16)
Authors: Tegla Cosmin , Cudrici Cornelia , Singh Anil , Vlaicu Sonia , Nguyen Vinh , Rus Violeta , Rus Horea 
Published: January 2023

Abstract
Later stages of multiple sclerosis (MS) are characterized by a reduced number of inflammatory cells and an excessive accumulation of extracellular matrix (ECM) components, which leads to tissue fibrosis. Profibrotic cytokines such as TGF-beta stimulate the synthesis of ECM by astrocytes. However, the intracellular mechanism by which TGF-beta stimulates the production of ECM is not completely understood. We have identified Response Gene to Complement (RGC)-32 as a factor induced by complement activation, growth factors, cytokines and TGF-beta. In view of the important role of TGF-beta in promotion of gliosis, we sought to determine whether RGC-32 plays a role in TGF-beta induced gliosis. RGC-32 was expressed at low levels in unstimulated astrocytes. After 3 h of TGF-beta stimulation, mRNA expression was significantly increased and after 18 h of treatment both the RGC-32 mRNA and protein expression levels were robustly increased when compared with controls. RGC-32 knockdown resulted in a significant reduction in procollagen I, procollagen II and fibronectin expression induced by TGF-beta. In addition, using chromatin immunoprecipitation assay we have shown the in vivo binding of RUNX1 to the RGC-32 promoter after TGF-beta stimulation. Taken together, our data demonstrate for the first time that RGC-32 plays a critical role in TGF-beta-induced ECM production in astrocytes. Our study suggests that RGC-32 can be a new target for therapeutic intervention to prevent gliosis in MS.
Deficiency of leukocyte NADPH oxidase increases joint inflammation in serum-induced arthritis model (44.27)
Authors: Huang Ya-Fang , Nigrovic Peter , Shieh Chi-Chang 
Published: January 2023

Abstract
To elucidate the role of reactive oxygen species (ROS) in modulating tissue inflammation, we established an arthritis model by intraperitoneally injecting the K/BxN serum into wild type and ncf1-/- CGD mice, which have deficiency in p47phox of NOX2. By comparing the joint inflammation index ankle thickening, we found that the serum-induced arthritis were more severe in CGD mice than in wild type mice (30.2 mm ± 4.6 vs. 19.6 mm ± 0.19 on the day 10). These data suggested that lack of leukocyte-produced ROS interferes with the control of the neutrophil-dominant joint inflammation. By depleting neutrophils with anti-Ly6G antibodies, we found that serum-induced arthritis was abrogated in both ncf1-/- and wild type mice, which confirms previous reports that neutrophils play an important role in the induction and progression of serum-induced arthritis. However, the joint reaction in serum-induced diseased ncf1-/- mice, different from wild type mice, could not be reversed by depleting neutrophils. We further analyzed the proinflammatory cytokines, chemokines, and neutrophil-related proteases in ncf1-/- mice and wild type. We also analyzed the redox modulation status of redox response proteins to elucidate the possible mechanisms involved in ROS-mediated innate immunity in regulating the joint inflammation. These data suggest that ROS play an important role in modulating immune system and controlling the tissue inflammation in joints.
Quantitative imbalance and functional defects of myeloid-derived suppressor cells in the NOD mouse model of autoimmune diabetes (44.39)
Authors: Adeegbe Dennis , Ricordi Camillo , Serafini Paolo , Inverardi Luca 
Published: January 2023

Abstract
Myeloid-derived suppressor cells (MDSCs) contribute to tumor escape by inhibiting tumor-specicif T cell response and accumulate at peripheral sites during inflammation or tissue damage. While accumulating evidence supports MDSC’s ability to suppress T cell responses against auto antigens, it is currently unknown whether they exhibit intrinsic defects in autoimmune disease conditions. Thus, the present study evaluated quantitative and qualitative properties of MDSCs in diabetes-prone NOD mice relative to healthy wild type (wt) control animals. FACS analysis revealed a higher fraction of Gr-1+CD11b+ MDSCs that further increased with diabetes incidence in the peripheral blood of NOD mice compared to controls. Although NOD MDSCs were similar phenotypically to their wt counterparts, an imbalanced ratio between the monocytic (LY6C+) and granulocytic (Ly6Ghi) subsets was prevalent in the NOD mice (1:15 vs 1:1.5 in controls). Importantly, MDSCs isolated from NOD mice demonstrated diminished suppressive capability in vitro compared to wt cells, consistent with their expression of lower levels of iNOS mRNA. In a diabetes transfer model, wild type but not NOD MDSCs significantly delayed disease occurrence in NOD.Scid recipients. Collectively, these data indicate a quantitative perturbation in MDSC subsets in NOD mice and suggest qualitative defects that may represent a previously un-identified mechanism in the etiology or progression of disease in this animal model of type 1 diabetes.
Anti-lipid response in Systemic Lupus Erythematosus (44.4)
Authors: Jovanovic Vojislav , Ng Ai Poh Amanda , Ho Xin Pei Eliza , Lim Yan Ting , Abdul Aziz Nurhuda , McKinney Eoin , Lyons Paul , Smith Kenneth , MacAry Paul , Kemeny Michael , Wenk Markus 
Published: January 2023

Abstract
Systemic Lupus Erythematosus (SLE) is a chronic, multisystem, autoimmune disorder with a broad range of clinical presentations. One of the main factors, proposed to contribute to the development of clinical manifestations of SLE is accumulation and impaired clearance of immune complexes. The aim of the present study was to investigate lipid and anti-lipid antibody profiles in SLE patients’ plasma using ELISA and gas chromatography-mass spectrometry (GC-MS). The SLE cohort employed in this study is composed of 24 subjects and disease monitoring was undertaken with serial BILAG disease scoring. The blood was collected at three time points: at the moment of flare; and 3-months/12-months after treatment had started. For oxysterols (7α-hydroxycholesterol, 7β-hydroxycholesterol, 7-ketocholesterol) we report a trend where lipid levels and corresponding anti-lipid IgG concentrations are significantly reduced during the course of treatment. For phospholipids (oxidized phosphatidylcholine, cardiolipin) we also show high levels of anti-lipid IgG during flare or active disease. Using GC-MS and ELISA we have confirmed an association of high lipid levels and high anti-lipid IgG level with disease flare in comparison to 12 months after the commencement of treatment. We propose that auto anti-lipid IgGs should now be considered a component of the accumulated immune complexes in SLE and thus may contribute to disease pathogenesis.
Non-invasive imaging of arthritic inflammation and therapeutic response with 19F MRI (44.42)
Authors: Wesa Amy , Balducci Anthony , Helfer Brooke , Ahrens Eric , O'Hanlon Charlie 
Published: January 2023

Abstract
Non-invasive imaging of inflammation to diagnose diseases such as rheumatoid arthritis (RA) and to monitor responses to therapy is critically needed. V-Sense, a perfluorocarbon tracer agent that preferentially labels inflammatory cells, which are then recruited out of systemic circulation to sites of inflammation, enables detection by 19F MRI. With no 19F background in the host, detection is highly-specific, yielding a quantitative marker of the degree of inflammation present. Collagen-induced arthritis in rats, a model with many similarities to human RA, was used to study the ability of V-Sense to measure the accumulation of inflammation over time. Disease progression in the rat hind limbs was monitored by caliper measurements and 19F MRI on days 14, 21 and 28, including the height of clinically symptomatic disease. Naïve rats served as controls. The capacity of V-Sense to assess the effectiveness of therapy was studied in a cohort of rats administered oral prednisolone on days 14 to 28. This study may support the use of V-Sense to clinically quantify and monitor the severity of inflammation, and to assess the effectiveness of treatments in RA and other diseases with an inflammatory component