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https://www.readbyqxmd.com/read/29141888/lung-cancer-associated-pulmonary-hypertension-role-of-microenvironmental-inflammation-based-on-tumor-cell-immune-cell-cross-talk
#1
Soni Savai Pullamsetti, Baktybek Kojonazarov, Samantha Storn, Henning Gall, Ylia Salazar, Janine Wolf, Andreas Weigert, Nefertiti El-Nikhely, Hossein Ardeschir Ghofrani, Gabriele A Krombach, Ludger Fink, Stefan Gattenlöhner, Ulf R Rapp, Ralph Theo Schermuly, Friedrich Grimminger, Werner Seeger, Rajkumar Savai
Dyspnea is a frequent, devastating, and poorly understood symptom of advanced lung cancer. In our cohort, among 519 patients who underwent a computed tomography scan for the diagnosis of lung cancer, 250 had a mean pulmonary artery diameter of >28 mm, indicating pulmonary hypertension (PH). In human lung cancer tissue, we consistently observed increased vascular remodeling and perivascular inflammatory cell accumulation (macrophages/lymphocytes). Vascular remodeling, PH, and perivascular inflammatory cell accumulation were mimicked in three mouse models of lung cancer (LLC1, KRas(LA2) , and cRaf-BxB)...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29141886/pd-l1-genetic-overexpression-or-pharmacological-restoration-in-hematopoietic-stem-and-progenitor-cells-reverses-autoimmune-diabetes
#2
Moufida Ben Nasr, Sara Tezza, Francesca D'Addio, Chiara Mameli, Vera Usuelli, Anna Maestroni, Domenico Corradi, Silvana Belletti, Luca Albarello, Gabriella Becchi, Gian Paolo Fadini, Christian Schuetz, James Markmann, Clive Wasserfall, Leonard Zon, Gian Vincenzo Zuccotti, Paolo Fiorina
Immunologically based clinical trials performed thus far have failed to cure type 1 diabetes (T1D), in part because these approaches were nonspecific. Because the disease is driven by autoreactive CD4 T cells, which destroy β cells, transplantation of hematopoietic stem and progenitor cells (HSPCs) has been recently offered as a therapy for T1D. Our transcriptomic profiling of HSPCs revealed that these cells are deficient in programmed death ligand 1 (PD-L1), an important immune checkpoint, in the T1D nonobese diabetic (NOD) mouse model...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29137359/granulysin-expressed-in-a-humanized-mouse-model-induces-apoptotic-cell-death-and-suppresses-tumorigenicity
#3
Ya-Wen Hsiao, Tsung-Ching Lai, Yu-Hsiang Lin, Chia-Yi Su, Jih-Jong Lee, Albert Taiching Liao, Yuan-Feng Lin, Shu-Chen Hsieh, Alexander T H Wu, Michael Hsiao
Granulysin (GNLY) is a cytolytic and proinflammatory protein expressed in activated human cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Conventional mouse models cannot adequately address the triggering mechanism and immunopathological pathways in GNLY-associated diseases due to lack of the GNLY gene in the mouse genome. Therefore, we generated a humanized immune system (HIS) mouse model by transplanting human umbilical cord blood mononuclear cells into NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl) /SzJ (NSG) mice after sublethally irradiation...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135340/generation-and-testing-anti-influenza-human-monoclonal-antibodies-in-a-new-humanized-mouse-model-draga-hla-a2-hla-dr4-rag1-ko-il-2r%C3%AE-c-ko-nod
#4
Mirian Mendoza, Angela Ballesteros, Qiu Qi, Luis Pow Sang, Soumya Shashikumar, Sofia Casares, Teodor-D Brumeanu
Pandemic outbreaks of influenza type A viruses have resulted in numerous fatalities around the globe. Since the conventional influenza vaccines (CIV) provide less than 20% protection for individuals with weak immune system, it has been considered that broadly cross-neutralizing antibodies may provide a better protection. Herein, we showed that a recently generated humanized mouse (DRAGA mouse; HLA-A2. HLA-DR4. Rag1KO. IL-2Rγc KO. NOD) that lacks the murine immune system and expresses a functional human immune system can be used to generate cross-reactive, human anti-influenza monoclonal antibodies (hu-mAb)...
November 14, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29128556/pro-140-monoclonal-antibody-to-ccr5-prevents-acute-xenogeneic-graft-versus-host-disease-in-nod-scid-il-2ry-null-mice
#5
Denis R Burger, Yvonne Parker, Kathryn Guinta, Daniel Lindner
Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication of hematopoietic stem cell transplantation (HSCT). Humanized mouse models of xenogeneic-GvHD are important tools used to study the human immune response in vivo. Here we used NOD-scid IL-2Ry(null) mice (NSG) transplanted with human bone marrow stem cells to evaluate the role of immune cell engraftment in the production of acute GvHD. PRO 140, a humanized monoclonal antibody targeting the chemokine receptor, CCR5, was used to evaluate its influence on bone marrow cell engraftment and modulation of acute GvHD...
November 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29127409/frequency-of-human-cd45-target-cells-is-a-key-determinant-of-intravaginal-hiv-1-infection-in-humanized-mice
#6
Philip V Nguyen, Jocelyn M Wessels, Kristen Mueller, Fatemeh Vahedi, Varun Anipindi, Chris P Verschoor, Marianne Chew, Alexandre Deshiere, Uladzimir Karniychuk, Tony Mazzulli, Michel J Tremblay, Ali A Ashkar, Charu Kaushic
Approximately 40% of HIV-1 infections occur in the female genital tract (FGT), primarily through heterosexual transmission. FGT factors determining outcome of HIV-1 exposure are incompletely understood, limiting prevention strategies. Here, humanized NOD-Rag1(-/-) γc(-/-) mice differentially reconstituted with human CD34+ -enriched hematopoietic stem cells (Hu-mice), were used to assess target cell frequency and viral inoculation dose as determinants of HIV-1 infection following intravaginal (IVAG) challenge...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29119053/enzalutamide-as-an-androgen-receptor-inhibitor-prevents-urothelial-tumorigenesis
#7
Takashi Kawahara, Satoshi Inoue, Eiji Kashiwagi, Jinbo Chen, Hiroki Ide, Taichi Mizushima, Yi Li, Yichun Zheng, Hiroshi Miyamoto
Emerging preclinical evidence suggests the critical role of androgen-mediated androgen receptor (AR) signals in the development of bladder cancer. However, little is known about the efficacy of enzalutamide, an AR signaling inhibitor, in androgen-induced urothelial tumorigenesis. We therefore aimed to assess the effects of enzalutamide on neoplastic transformation of urothelial cells. An immortalized normal urothelial cell line SVHUC stably expressing wild-type AR (SVHUC-AR) was exposed to a chemical carcinogen 3-methylcholanthrene (MCA) to induce neoplastic transformation, and subsequently cultured for 6 weeks in the presence of anti-androgens, including enzalutamide, hydroxyflutamide, and bicalutamide...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29113292/nod-mice-susceptible-to-pancreatic-autoimmunity-demonstrate-delayed-growth-of-pancreatic-cancer
#8
James Dooley, Emanuela Pasciuto, Vasiliki Lagou, Yulia Lampi, Tom Dresselaers, Uwe Himmelreich, Adrian Liston
Pancreatic cancer is a high mortality form of cancer, with a median survival only six months. There are multiple associated risk factors associated, most importantly type 2 diabetes, obesity, pancreatitis and smoking. The relative rarity of the disease, however, has made it difficult to dissect causative risk factors, especially with related risk factors. A major unanswered question with important therapeutic implications is the effect of immunological responses on pancreatic cancer formation, with data from other cancers suggesting the potential for local immunological responses to either increase cancer development or increase cancer elimination...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29109122/the-type-1-diabetes-resistance-locus-idd22-controls-trafficking-of-autoreactive-ctls-into-the-pancreatic-islets-of-nod-mice
#9
Robert L Whitener, Lisa Gallo Knight, Jianwei Li, Sarah Knapp, Shuyao Zhang, Mani Annamalai, Vadim M Pliner, Dongtao Fu, Ilian Radichev, Christina Amatya, Alexei Savinov, Arif Yurdagul, Shuai Yuan, John Glawe, Christopher G Kevil, Jing Chen, Scott E Stimpson, Clayton E Mathews
Type 1 diabetes (T1D) has a strong genetic component. The insulin dependent diabetes (Idd)22 locus was identified in crosses of T1D-susceptible NOD mice with the strongly T1D-resistant ALR strain. The NODcALR-(D8Mit293-D8Mit137)/Mx (NOD-Idd22) recombinant congenic mouse strain was generated in which NOD mice carry the full Idd22 confidence interval. NOD-Idd22 mice exhibit almost complete protection from spontaneous T1D and a significant reduction in insulitis. Our goal was to unravel the mode of Idd22-based protection using in vivo and in vitro models...
November 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29093987/targeting-the-epitope-spreader-pep19-by-na%C3%A3-ve-human-cd45ra-regulatory-t-cells-dictates-a-distinct-suppressive-t-cell-fate-in-a-novel-form-of-immunotherapy
#10
Hyun-Joo Kim, Gil Sun Cha, Ji-Young Joo, Juyoun Lee, Sung-Jo Kim, Jeongae Lee, So Youn Park, Jeomil Choi
Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. Methods: Human polyclonal CD4(+)CD25(+)CD127(lo-) Tregs (127-Tregs) and naïve CD4(+)CD25(+)CD45RA(+) Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion...
October 2017: Journal of Periodontal & Implant Science
https://www.readbyqxmd.com/read/29080983/autoimmune-responses-to-exosomes-and-candidate-antigens-contribute-to-type-1-diabetes-in-non-obese-diabetic-mice
#11
REVIEW
Yang D Dai, Huiming Sheng, Peter Dias, M Jubayer Rahman, Roman Bashratyan, Danielle Regn, Kristi Marquardt
PURPOSE OF REVIEW: The initial autoimmune trigger of type 1 diabetes (T1D) remains unclear. In non-obese diabetic (NOD) mice, islet inflammation starts early in life, suggesting the presence of an endogenous trigger for the spontaneous autoimmune response in this T1D mouse model. In this review, we argue that abnormal release of exosomes might be the trigger of the early inflammatory and autoimmune responses in the islets. RECENT FINDINGS: Exosomes are nano-sized membrane complexes that are secreted by cells following fusion of late endosomes and/or multivesicular bodies with the plasma membrane...
October 28, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/29062479/murine-genotype-impacts-pancreatitis-severity-and-systemic-inflammation-an-experimental-study
#12
Gabriel J Seifert, Karoline C Sander, Sabine Richter, Uwe A Wittel
BACKGROUND: Little is known regarding the impact of host response in acute pancreatitis. Here, we induce murine necrotizing pancreatitis in 9 different mouse strains. MATERIALS AND METHODS: We examined 9 different mouse strains: Balb/CB4J, C3H/HEJ, NOD/SHILT, A/J, AKR/J, C57BI/6J, DBA/2J, FVB/NJ, 129S1/SvlmJ. 10 animals per strain were randomly allotted to two groups. Sterile necrotizing pancreatitis was induced by injection of taurocholate into the common bile duct...
December 2017: Annals of Medicine and Surgery
https://www.readbyqxmd.com/read/29058172/the-expression-of-dectin-1-irak1-and-rip2-during-the-host-response-to-aspergillus-fumigatus
#13
Jinguo Liu, Lin Yu, Cuicui Chen, Jian Zhou, Xin Gong, Dandan Li, Dongni Hou, Yuanlin Song, Changzhou Shao
BACKGROUND: C-type lectin receptors (CLRs), Toll-like receptors (TLRs), and Nod-like receptors (NLRs) have the ability to recognize Aspergillus fumigatus (A. fumigates) and induce innate immune response. Dectin-1 is a well-described CLR, while interleukin-1 receptor-associated kinase 1 (Irak1) and receptor-interacting protein 2 (Rip2) are pivotal adaptor proteins of TLRs and NLRs signaling pathways, respectively. OBJECTIVES: Our primary aim is to elucidate whether Dectin-1 regulates the expression of Irak1 and Rip2, and confirm that CLRs, TLRs, and NLRs pathways act synergistically in response to A...
October 23, 2017: Mycopathologia
https://www.readbyqxmd.com/read/29056548/human-induced-pluripotent-stem-cell-derived-lung-progenitor-and-alveolar-epithelial-cells-attenuate-hyperoxia-induced-lung-injury
#14
Mehdi Shafa, Lavinia Iuliana Ionescu, Arul Vadivel, Jennifer J P Collins, Liqun Xu, Shumei Zhong, Martin Kang, Geneviève de Caen, Manijeh Daneshmand, Jenny Shi, Katherine Z Fu, Andrew Qi, Ying Wang, James Ellis, William L Stanford, Bernard Thébaud
BACKGROUND AIMS: Bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by disrupted lung growth, is the most common complication in extreme premature infants. BPD leads to persistent pulmonary disease later in life. Alveolar epithelial type 2 cells (AEC2s), a subset of which represent distal lung progenitor cells (LPCs), promote normal lung growth and repair. AEC2 depletion may contribute to persistent lung injury in BPD. We hypothesized that induced pluripotent stem cell (iPSC)-derived AECs prevent lung damage in experimental oxygen-induced BPD...
October 20, 2017: Cytotherapy
https://www.readbyqxmd.com/read/29055716/attenuation-of-mechanical-pain-hypersensitivity-by-treatment-with-peptide5-a-connexin-43-mimetic-peptide-involves-inhibition-of-nlrp3-inflammasome-in-nerve-injured-mice
#15
Ryan S Tonkin, Callum Bowles, Chamini J Perera, Brooke A Keating, Preet G S Makker, Samuel S Duffy, Justin G Lees, Collin Tran, Anthony S Don, Thomas Fath, Lu Liu, Simon J O'Carroll, Louise F B Nicholson, Colin R Green, Catherine Gorrie, Gila Moalem-Taylor
Connexin43 (Cx43) hemichannels in spinal cord astrocytes are implicated in the maintenance of neuropathic pain following peripheral nerve injury. Peptide5 is a Cx43 mimetic peptide that blocks hemichannels. In this study, we investigated the effects of spinal delivery of Peptide5 on mechanical pain hypersensitivity in two mouse models of neuropathic pain, peripheral nerve injury and chemotherapy-induced peripheral neuropathy (CIPN). We demonstrated that 10days following a chronic constriction injury (CCI) of the sciatic nerve, Cx43 expression, co-localised predominantly with astrocytes, was increased in the ipsilateral L3-L5 lumbar spinal cord...
October 18, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29052174/phagocytosis-deficiency-of-macrophages-in-nod-h-2-h4-mice-accelerates-the-severity-of-iodine-induced-autoimmune-thyroiditis
#16
Xue He, Chuhui Xiong, Aihua Liu, Wei Zhao, Xinghai Xia, Shiqiao Peng, Chenyan Li, Mi Zhou, Yushu Li, Xiaoguang Shi, Zhongyan Shan, Weiping Teng
Apoptosis occurs in many autoimmune diseases. Excess iodine induces thyrocyte apoptosis and increases the incidence and prevalence of autoimmune thyroiditis (AIT). However, the sequence of events between the appearance of thyrocyte apoptosis and the occurrence of thyroiditis remains uncharacterized. Furthermore, few studies have investigated the role of macrophage phagocytosis in the development of AIT. Therefore, we evaluated the relationship between apoptosis and inflammatory infiltration in NOD.H-2(h4) mouse thyroids by comparing the sequence of events in tissue samples...
October 20, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/29050075/-specific-cytotoxicity-of-a-novel-her2-based-chimeric-antigen-receptor-modified-t-lymphocytes-against-her2-positive-tumor-cells
#17
H J Tang, Y Q Liu, X C Bian, H L Feng, B Gu, H Sun, C X Zuo, F Y Zhou, J Liu
Objective: To construct the third generation chimeric antigen receptor based on a novel humanized anti-HER2 H1-2 scFv, and to investigate the specific cytotoxicity of H1-2 CAR modified T lymphocytes(CAR-T) against HER2(+) tumor cells. Method: The expression cassette of the third generation CAR gene and anti-HER2 H1-2 scFv were constructed and cloned into lentivirus transfer plasmid, and then the third generation H1-2 CAR was transduced into human T lymphocytes using lentivirus.Enzyme linked immunosorbent assay was used to detect the expression of cytokines IL2, and LDH release assay was used to detect the cytotoxic effect of the H1-2 CAR-T...
October 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29038571/highly-sensitive-and-specific-alu-based-quantification-of-human-cells-among-rodent-cells
#18
Kodai Funakoshi, Mozhdeh Bagheri, Ming Zhou, Ryoji Suzuki, Hiroshi Abe, Hideo Akashi
Alu elements are primate-specific short interspersed elements (SINEs), over 1 million copies of which are present in the human genome; thus, Alu elements are useful targets for detecting human cells. However, previous Alu-based techniques for detecting human genomic DNA do not reach the theoretical limits of sensitivity and specificity. In this study, we developed a highly sensitive and specific Alu-based real-time PCR method for discriminating human cells from rodent cells, using a primer and probe set carefully designed to avoid possible cross-reactions with rodent genomes...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29038005/prednisone-alleviates-demyelination-through-regulation-of-the-nlrp3-inflammasome-in-a-c57bl-6-mouse-model-of-cuprizone-induced-demyelination
#19
Hao Yu, Mingfeng Wu, Geng Lu, Tingting Cao, Nan Chen, Yijia Zhang, Higuo Jiang, Hongbin Fan, Ruiqin Yao
Myelin abnormalities, oligodendrocyte damage, and concomitant glia activation are common in demyelinating diseases of the central nervous system (CNS). Increasing evidence has demonstrated that the inflammatory response triggers demyelination and gliosis in demyelinating disorders. Numerous clinical interventions, including those used to treat multiple sclerosis (MS), have confirmed prednisone (PDN) as a powerful anti-inflammatory drug that reduces the inflammatory response and promotes tissue repair in multiple inflammation sites...
October 13, 2017: Brain Research
https://www.readbyqxmd.com/read/28994599/a-metabolomics-and-lipidomics-study-of-mouse-models-of-type-1-diabetes-highlights-divergent-metabolism-in-purine-and-tryptophan-metabolism-prior-to-disease-on-set
#20
Steven A Murfitt, Paula Zaccone, Xinzhu Wang, Animesh Acharjee, Yvonne Sawyer, Albert Koulman, Lee D Roberts, Anne Cooke, Julian Griffin
With the increase in incidence of type 1 diabetes (T1DM), particularly in Westernised societies, there is an urgent need to understand the early molecular and metabolic alterations that accompany the autoimmune disease. This is not least because in murine models early intervention can prevent the development of overt disease. In this study we have applied a liquid chromatography (LC-) and gas chromatography (GC-) mass spectrometry (MS) metabolomics and lipidomics analysis of blood plasma and pancreas tissue extracts to follow the progression of disease in three models related to autoimmune diabetes: the non-obese diabetic (NOD) mouse, which is susceptible to the development of autoimmune diabetes, and the NOD-E (transgenic NOD mice that express the I-E heterodimer of the major histocompatibility complex II) and NOD- severe combined immunodeficiency (SCID) mouse strains, two models protected from the development of diabetes...
October 10, 2017: Journal of Proteome Research
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