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JOURNAL ARTICLE
Corrado Mazzaglia, Hafsa Munir, Iek M Le, Magda Gerigk, Yan Yan Shery Huang, Jacqueline D Shields
Lymph nodes (LNs) are organs of the immune system, critical for maintenance of homeostasis and initiation of immune responses, yet there are few models that accurately recapitulate LN functions in vitro. To tackle this issue, an engineered murine LN (eLN) was developed, replicating key cellular components of the mouse LN; incorporating primary murine lymphocytes, fibroblastic reticular cells (FRCs), and lymphatic endothelial cells (LECs). T and B cells compartments are incorporated within the eLN that mimic LN cortex and paracortex architectures...
April 16, 2024: Advanced Healthcare Materials
#22
JOURNAL ARTICLE
Kevin MingJie Gao, Kristy Chiang, Zhaozhao Jiang, Filiz T Korkmaz, Harish P Janardhan, Chinmay M Trivedi, Lee J Quinton, Sebastien Gingras, Katherine A Fitzgerald, Ann Marshak-Rothstein
Patients afflicted with Stimulator of interferon gene (STING) gain-of-function mutations frequently present with debilitating interstitial lung disease (ILD) that is recapitulated in mice expressing the STINGV154M mutation (VM). Prior radiation chimera studies revealed an unexpected and critical role for non-hematopoietic cells in initiating ILD. To identify STING-expressing non-hematopoietic cell types required for the development of ILD, we use a conditional knockin (CKI) model and direct expression of the VM allele to hematopoietic cells, fibroblasts, epithelial cells, or endothelial cells...
April 15, 2024: Cell Reports
#23
JOURNAL ARTICLE
Néstor de la Visitación, Wei Chen, Jaya Krishnan, Justin P Van Beusecum, Venkataraman Amarnath, Elizabeth M Hennen, Shilin Zhao, Mohammad Saleem, Mingfang Ao, Sergey I Dikalov, Anna E Dikalova, David G Harrison, David M Patrick
BACKGROUND: Hypertension is characterized by CD8+ T cell activation and infiltration into peripheral tissues. CD8+ T cell activation requires proteasomal processing of antigenic proteins. It has become clear that isoLG (isolevuglandin)-adduced peptides are antigenic in hypertension; however, IsoLGs inhibit the constitutive proteasome. We hypothesized that immunoproteasomal processing of isoLG-adducts is essential for CD8+ T cell activation and inflammation in hypertension. METHODS: IsoLG adduct processing was studied in murine dendritic cells (DCs), endothelial cells (ECs), and B8 fibroblasts...
April 16, 2024: Circulation Research
#24
JOURNAL ARTICLE
Lufei Ren, Yuyang Li, Yifan Feng, Zhe Zhang, Huijun Yang, Min Li
BACKGROUND: Chloride channel-3 ( CLCN3 ), a crucial component of the voltage-gated chloride channel family, is implicated in numerous physiological and pathophysiological processes. This study aimed to investigate the characteristics of CLCN3 in pancancer and its influence on the immune response through the use of a range of databases. Concurrently, we assessed the impact of CLCN3 on the proliferation of ovarian cancer (OC) cells and explored its potential mechanisms. METHODS: We employed the Tumor Immune Estimation Resource (TIMER) 2...
March 31, 2024: Translational Cancer Research
#25
JOURNAL ARTICLE
Divya Pidishetty, Savitri Maddileti, Sudipta Mahato, Trupti Agrawal, Vinay Kumar Pulimamidi, Milind Naik, Chitra Kannabiran, Subhadra Jalali, Indumathi Mariappan
Mutations in ABCA4 gene leads to the most common form of an inherited retinal disease namely, the Stargardt disease, type 1. Here, we report the generation of two different patient-specific induced pluripotent stem cell lines (LVPEIi007-B and LVPEIi008-B), carrying an identical homozygous mutation, (c.6088C>T) within the exon 44 of ABCA4 gene. These lines were generated by the reprogramming of patient-specific dermal fibroblasts, using the integration-free, Sendai viral vectors. Both lines were stably expanded and expressed the stemness and pluripotency markers, differentiated into cell types of all three germ layers, and maintained a normal karyotype...
April 9, 2024: Stem Cell Research
#26
JOURNAL ARTICLE
Hui Tang, Tingting You, Hui Ge, Jingxi Gao, Yingyi Wang, Chunmei Bai, Zhao Sun, Qin Han, Robert Chunhua Zhao
Although PD-1 inhibitors have revolutionized the treatment paradigm of non-small cell lung cancer (NSCLC), their efficacy in treating NSCLC has remained unsatisfactory. Targeting cancer-associated fibroblasts (CAFs) is a potential approach for improving the immunotherapy response. Multitarget antiangiogenic tyrosine kinase receptor inhibitors (TKIs) can enhance the efficacy of PD-1 inhibitors in NSCLC patients. However, the effects and mechanisms of antiangiogenic TKIs on CAFs have not been elucidated. In this study, we first compared anlotinib with other antiangiogenic TKIs and confirmed the superior efficacy of anlotinib...
April 12, 2024: International Immunopharmacology
#27
JOURNAL ARTICLE
Yishu Wang, Xiaomin Chen, Ningjun Tang, Mengyao Guo, Dongmei Ai
Clear cell renal carcinoma (ccRCC), the most common subtype of renal cell carcinoma, has the high heterogeneity of a highly complex tumor microenvironment. Existing clinical intervention strategies, such as target therapy and immunotherapy, have failed to achieve good therapeutic effects. In this article, single-cell transcriptome sequencing (scRNA-seq) data from six patients downloaded from the GEO database were adopted to describe the tumor microenvironment (TME) of ccRCC, including its T cells, tumor-associated macrophages (TAMs), endothelial cells (ECs), and cancer-associated fibroblasts (CAFs)...
April 8, 2024: International Journal of Molecular Sciences
#28
JOURNAL ARTICLE
Thibault Gendron, Don Antoine Lanfranchi, Nicole I Wenzel, Hripsimée Kessedjian, Beate Jannack, Louis Maes, Sandrine Cojean, Thomas J J Müller, Philippe M Loiseau, Elisabeth Davioud-Charvet
2,6-Diaryl-4 H -tetrahydro-thiopyran-4-ones and corresponding sulfoxide and sulfone derivatives were designed to lower the major toxicity of their parent anti-kinetoplatidal diarylideneacetones through a prodrug effect. Novel diastereoselective methodologies were developed and generalized from diarylideneacetones and 2,6-diaryl-4 H -tetrahydro-thiopyran-4-ones to allow the introduction of a wide substitution profile and to prepare the related S -oxides. The in vitro biological activity and selectivity of diarylideneacetones, 2,6-diaryl-4 H -tetrahydro-thiopyran-4-ones, and their S -sulfoxide and sulfone metabolites were evaluated against Trypanosoma brucei brucei , Trypanosoma cruzi , and various Leishmania species in comparison with their cytotoxicity against human fibroblasts h MRC-5...
April 4, 2024: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
#29
JOURNAL ARTICLE
Hirotsugu Oda, Kalpana Manthiram, Pallavi Pimpale Chavan, Eva Rieser, Önay Veli, Öykü Kaya, Charles Rauch, Shuichiro Nakabo, Hye Sun Kuehn, Mariël Swart, Yanli Wang, Nisa Ilgim Çelik, Anne Molitor, Vahid Ziaee, Nasim Movahedi, Mohammad Shahrooei, Nima Parvaneh, Nasrin Alipour-Olyei, Raphael Carapito, Qin Xu, Silvia Preite, David B Beck, Jae Jin Chae, Michele Nehrebecky, Amanda K Ombrello, Patrycja Hoffmann, Tina Romeo, Natalie T Deuitch, Brynja Matthíasardóttir, James Mullikin, Hirsh Komarow, Jennifer Stoddard, Julie Niemela, Kerry Dobbs, Colin L Sweeney, Holly Anderton, Kate E Lawlor, Hiroyuki Yoshitomi, Dan Yang, Manfred Boehm, Jeremy Davis, Pamela Mudd, Davide Randazzo, Wanxia Li Tsai, Massimo Gadina, Mariana J Kaplan, Junya Toguchida, Christian T Mayer, Sergio D Rosenzweig, Luigi D Notarangelo, Kazuhiro Iwai, John Silke, Pamela L Schwartzberg, Bertrand Boisson, Jean-Laurent Casanova, Seiamak Bahram, Anand Prahalad Rao, Nieves Peltzer, Henning Walczak, Najoua Lalaoui, Ivona Aksentijevich, Daniel L Kastner
The linear ubiquitin assembly complex (LUBAC) consists of HOIP, HOIL-1 and SHARPIN and is essential for proper immune responses. Individuals with HOIP and HOIL-1 deficiencies present with severe immunodeficiency, autoinflammation and glycogen storage disease. In mice, the loss of Sharpin leads to severe dermatitis due to excessive keratinocyte cell death. Here, we report two individuals with SHARPIN deficiency who manifest autoinflammatory symptoms but unexpectedly no dermatological problems. Fibroblasts and B cells from these individuals showed attenuated canonical NF-κB responses and a propensity for cell death mediated by TNF superfamily members...
April 12, 2024: Nature Immunology
#30
JOURNAL ARTICLE
Raymond J So, Samuel L Collins, Yee Chan-Li, Ioan Lina, Alexander Gelbard, Kevin M Motz, Alexander T Hillel
OBJECTIVE: To present a comprehensive flow cytometry panel for idiopathic subglottic stenosis (iSGS). STUDY DESIGN: Controlled ex vivo cohort study. SETTING: Tertiary care academic hospital in a metropolitan area. METHODS: Flow cytometry and single-cell RNA sequencing were performed on 9 paired normal and scar tissue samples from iSGS patients. Flow cytometry was used to assess the presence of myeloid (CD11b, CD14, CD15, Siglec8), lymphoid (CD3, CD4, CD8, gamma delta [γδ], FOXP3), endothelial (CD31), fibroblast (CD90, SMA), and epithelial (CD326, CK5) markers...
April 12, 2024: Otolaryngology—Head and Neck Surgery
#31
JOURNAL ARTICLE
Abdulmohammad Pezeshki, John C Cheville, Angela B Florio, Bradley C Leibovich, George Vasmatzis
BACKGROUND: Only 20 percent of renal and bladder cancer patients will show a significant response to immune checkpoint inhibitor (ICI) therapy, and no test currently available accurately predicts ICI response. METHODS: We developed an "immunotumoroid" cell model system that recapitulates the tumor, its microenvironment, and necessary immune system components in patient-derived spheroids to enable ex vivo assessment of tumor response to ICI therapy. Immunotumoroids were developed from surgically resected renal cell carcinomas and bladder carcinomas selected for high tumor-infiltrating lymphocytes (TILs) and survived more than a month without media exchange...
2024: Frontiers in Immunology
#32
JOURNAL ARTICLE
M C I Labonia, M Estapé Senti, P H van der Kraak, M A D Brans, I Dokter, T J Streef, A M Smits, A K Deshantri, S C A de Jager, R M Schiffelers, J P G Sluijter, P Vader
Despite research efforts being made towards preserving (or even regenerating) heart tissue after an ischemic event, there is a lack of resources in current clinical treatment modalities for patients with acute myocardial infarction that specifically address cardiac tissue impairment. Modified messenger RNA (modRNA) presents compelling properties that could allow new therapeutic strategies to tackle the underlying molecular pathways that ultimately lead to development of chronic heart failure. However, clinical application of modRNA for the heart is challenged by the lack of effective and safe delivery systems...
April 9, 2024: Journal of Controlled Release
#33
REVIEW
Pei-Rong Gan, Hong Wu, Yu-Long Zhu, Yin Shu, Yi Wei
Resident synoviocytes and synovial microvasculature, together with immune cells from circulation, contribute to pannus formation, the main pathological feature of rheumatoid arthritis (RA), leading to destruction of adjacent cartilage and bone. Seeds, fibroblast-like synoviocytes (FLSs), macrophages, dendritic cells (DCs), B cells, T cells and endothelial cells (ECs) seeds with high metabolic demands undergo metabolic reprogramming from oxidative phosphorylation to glycolysis in response to poor soil of RA synovium with hypoxia, nutrient deficiency and inflammatory stimuli...
April 9, 2024: International Immunopharmacology
#34
JOURNAL ARTICLE
Anamarija Jurisic, Pei-Ju Sung, Mark Wappett, Julien Daubriac, Ian T Lobb, Wei-Wei Kung, Nyree Crawford, Natalie Page, Eamon Cassidy, Stephanie Feutren-Burton, J S Shane Rountree, Matthew D Helm, Colin R O'Dowd, Richard D Kennedy, Gerald Gavory, Aaron N Cranston, Daniel B Longley, Xavier Jacq, Timothy Harrison
BACKGROUND: Understanding how to modulate the microenvironment of tumors that are resistant to immune checkpoint inhibitors represents a major challenge in oncology.Here we investigate the ability of USP7 inhibitors to reprogram the tumor microenvironment (TME) by inhibiting secretion of vascular endothelial growth factor (VEGF) from fibroblasts. METHODS: To understand the role played by USP7 in the TME, we systematically evaluated the effects of potent, selective USP7 inhibitors on co-cultures comprising components of the TME, using human primary cells...
April 2024: Clinical and Translational Medicine
#35
JOURNAL ARTICLE
Yitao Wang, Jundan Wang, Jing Jiang, Wei Zhang, Long Sun, Qidong Ge, Chao Li, Xinlin Li, Xujun Li, Shenghong Shi
INTRODUCTION: The close association between cuproptosis and tumor immunity in triple-negative breast cancer (TNBC) allows its monitoring for predicting the prognosis of patients with TNBC. Nevertheless, the biological function and prognostic value of cuproptosis-related miRNAs and their target genes have not been reported. PURPOSE: To construct the miRNA and mRNA-based risk models associated with cuproptosis for patients with TNBC. METHODS: Comparison of expression levels for genes associated with cuproptosis was executed between patients in the normal individuals and the TCGA-TNBC cohort...
April 15, 2024: Heliyon
#36
REVIEW
Margaret H Chang, Robert C Fuhlbrigge, Peter A Nigrovic
In rheumatoid arthritis, juvenile idiopathic arthritis and other forms of inflammatory arthritis, the immune system targets certain joints but not others. The pattern of joints affected varies by disease and by individual, with flares most commonly involving joints that were previously inflamed. This phenomenon, termed joint-specific memory, is difficult to explain by systemic immunity alone. Mechanisms of joint-specific memory include the involvement of synovial resident memory T cells that remain in the joint during remission and initiate localized disease recurrence...
April 10, 2024: Nature Reviews. Rheumatology
#37
REVIEW
Maddie Hasson, Lorenzo M Fernandes, Hanna Solomon, Tristan Pepper, Nicholas L Huffman, Saitheja A Pucha, Jason T Bariteau, Jarred M Kaiser, Jay M Patel
BACKGROUND: Marrow stimulation is a common reparative approach to treat injuries to cartilage and other soft tissues (e.g., rotator cuff). It involves the recruitment of bone marrow elements and mesenchymal stem cells (MSCs) into the defect, theoretically initiating a regenerative process. However, the resulting repair tissue is often weak and susceptible to deterioration with time. The populations of cells at the marrow stimulation site (beyond MSCs), and their contribution to inflammation, vascularity, and fibrosis, may play a role in quality of the repair tissue...
April 10, 2024: Cells, Tissues, Organs
#38
JOURNAL ARTICLE
H Chen, Z Li, M Wang, L Lu, Q Tang, L Luo
OBJECTIVE: To investigate the expression of the ubiquitination enzyme UBE2S in different cell types in hepatocellular carcinoma (HCC) microenvironment and its impact on proliferation and stemness of HCC cells. METHODS: TCGA and CPTAC database were used to analyze the transcriptional and promoter methylation levels and protein expressions of UBE2S in HCC. Specific expression patterns of UBE2S, intercellular communication and key transcription factors in different cell types were analyzed based on single-cell sequencing data from TISCH website...
March 20, 2024: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
#39
JOURNAL ARTICLE
Shenglan Li, Sen Zhao, Jefferson C Sinson, Aleksandar Bajic, Jill A Rosenfeld, Matthew B Neeley, Mezthly Pena, Kim C Worley, Lindsay C Burrage, Monika Weisz-Hubshman, Shamika Ketkar, William J Craigen, Gary D Clark, Seema Lalani, Carlos A Bacino, Keren Machol, Hsiao-Tuan Chao, Lorraine Potocki, Lisa Emrick, Jennifer Sheppard, My T T Nguyen, Anahita Khoramnia, Paula Patricia Hernandez, Sandesh Cs Nagamani, Zhandong Liu, Christine M Eng, Brendan Lee, Pengfei Liu
RNA sequencing (RNA-seq) has recently been used in translational research settings to facilitate diagnoses of Mendelian disorders. A significant obstacle for clinical laboratories in adopting RNA-seq is the low or absent expression of a significant number of disease-associated genes/transcripts in clinically accessible samples. As this is especially problematic in neurological diseases, we developed a clinical diagnostic approach that enhanced the detection and evaluation of tissue-specific genes/transcripts through fibroblast-to-neuron cell transdifferentiation...
April 3, 2024: American Journal of Human Genetics
#40
JOURNAL ARTICLE
Jyoti Kumari, Odile Paul, Lisa Verdellen, Bela Berking, Wen Chen, Lotte Gerrits, Jelle Postma, Frank A D T G Wagener, Paul H J Kouwer
Reliable in vitro models closely resembling native tissue are urgently needed for disease modeling and drug screening applications. Recently, conductive biomaterials have received increasing attention in the development of in vitro models as they permit exogenous electrical signals to guide cells toward a desired cellular response. Interestingly, they have demonstrated that they promote cellular proliferation and adhesion even without external electrical stimulation. This paper describes the development of a conductive, fully synthetic hydrogel based on hybrids of the peptide-modified polyisocyanide (PIC-RGD) and the relatively conductive poly(aniline- co - N -(4-sulfophenyl)aniline) (PASA) and its suitability as the in vitro matrix...
April 9, 2024: ACS Applied Bio Materials
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