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JOURNAL ARTICLE
Yafei Zhou, Rui Zhou, Wenjun Huang, Jie Wang, Congshan Jiang, Anmao Li, Christopher L H Huang, Yanmin Zhang
BACKGROUND AND OBJECTIVES: Gene expression, morphology, and electrophysiological combination are essential for assessing the dynamic development of human induced pluripotent stem cell-derived atrial- and ventricular-like cardiomyocytes (iPS-AM and iPS-VM, respectively). METHODS: For iPS-AM/VM differentiation, we performed the small molecule-based temporal modulation of the retinoic acid and bone morphogenetic protein signaling pathways. We investigated the gene expression and morphology using immunofluorescence, quantitative real-time polymerase chain reaction, flow cytometry, and transmission electron microscopy as well as registered electrophysiological functions using a whole-cell patch clamp on days 20, 30, and 60 post-differentiations...
2024: Biologics: Targets & Therapy
#62
JOURNAL ARTICLE
Admasu Haile Hantalo, Abera Kumalo Shano, Tekilu Israel Meja
BACKGROUND: The permanence of HIV patients in healthcare provision centers exposes their weak immunity to various nosocomial microorganisms that migrate into and out of the hospital environment. The incidence of bacterial infections, including urinary tract infection, was inversely correlated with CD4+ T cells. Urinary tract infection (UTI) is one of the clinical problems among HIV patients. There was scarcity of published data on the relationship between viral load, CD4+ level, and UTI...
2024: Frontiers in Microbiology
#63
Gabriel Aughey, Elisa Cali, Reza Maroofian, Maha S Zaki, Alistair T Pagnamenta, Fatima Rahman, Lara Menzies, Anum Shafique, Mohnish Suri, Emmanuel Roze, Mohammed Aguennouz, Zouiri Ghizlane, Saadia Maryam Saadi, Zafar Ali, Uzma Abdulllah, Huma Arshad Cheema, Muhammad Nadeem Anjum, Godelieve Morel, Robert McFarland, Umut Altunoglu, Verena Kraus, Moneef Shoukier, David Murphy, Kristina Flemming, Hilde Yttervik, Hajar Rhouda, Gaetan Lesca, Bibi Nazia Murtaza, Mujaddad Ur Rehman, Genomics England Consortium, Go Hun Seo, Christian Beetz, Hülya Kayserili, Yamna Krioulie, Wendy K Chung, Sadaf Naz, Shazia Maqbool, Joseph Gleeson, Shahid Mahmood Baig, Stephanie Efthymiou, Jenny C Taylor, Mariasavina Severino, James Ec Jepson, Henry Houlden
Retinoblastoma (RB) proteins are highly conserved transcriptional regulators that play important roles during development by regulating cell-cycle gene expression. RBL2 dysfunction has been linked to a severe neurodevelopmental disorder. However, to date, clinical features have only been described in six individuals carrying five biallelic predicted loss of function (pLOF) variants. To define the phenotypic effects of RBL2 mutations in detail, we identified and clinically characterized a cohort of 28 patients from 18 families carrying LOF variants in RBL2 , including fourteen new variants that substantially broaden the molecular spectrum...
May 5, 2024: medRxiv
#64
Mark Barry, Alpa Trivedi, Byron Miyazawa, Lindsay Vivona, David Shimmin, Praneeti Pathipati, Callie Keane, Joseph Cuschieri, Shibani Pati
BACKGROUND Patients with hemorrhagic shock and trauma (HS/T) are vulnerable to the endotheliopathy of trauma (EOT), characterized by vascular barrier dysfunction, inflammation, and coagulopathy. Cellular therapies such as mesenchymal stem cells (MSCs) and MSC extracellular vesicles (EVs) have been proposed as potential therapies targeting the EOT. In this study we investigated the effects of MSCs and MSC EVs on endothelial and epithelial barrier integrity in vitro and in vivo in a mouse model of HS/T. This study addresses systemic effects of HS/T on multiorgan EOT in HS/T model...
May 2, 2024: Research Square
#65
Stanley Riddell, Sylvain Simon, Grace Bugos, Rachel Prins, Anusha Rajan, Arulmozhi Palani, Kersten Heyer, Andrew Stevens, Longhui Zeng, Kirsten Thompson, Jason Price, Mitchell Kluesner, Carla Jaeger-Ruckstuhl, Tamer Shabaneh, James Olson, Xiaolei Su
The expression of a synthetic chimeric antigen receptor (CAR) to redirect antigen specificity of T cells is transforming the treatment of hematological malignancies and autoimmune diseases [1-7]. In cancer, durable efficacy is frequently limited by the escape of tumors that express low levels or lack the target antigen [8-12]. These clinical results emphasize the need for immune receptors that combine high sensitivity and multispecificity to improve outcomes. Current mono- and bispecific CARs do not faithfully recapitulate T cell receptor (TCR) function and require high antigen levels on tumor cells for recognition [13-17]...
April 22, 2024: Research Square
#66
Ana Rafaela Teixeira, Cintia Bittar, Gabriela S Silva Santos, Thiago Y Oliveira, Amy S Huang, Noemi Linden, Isabella A T M Ferreira, Tetyana Murdza, Frauke Muecksch, R Brad Jones, Marina Caskey, Mila Jankovic, Michel C Nussenzweig
HIV-1 anti-retroviral therapy is highly effective but fails to eliminate a reservoir of latent proviruses leading to a requirement for life-long treatment. How the site of integration of authentic intact latent proviruses might impact their own or neighboring gene expression or reservoir dynamics is poorly understood. Here we report on proviral and neighboring gene transcription at sites of intact latent HIV-1 integration in cultured T cells obtained directly from people living with HIV, as well as engineered primary T cells and cell lines...
April 29, 2024: bioRxiv
#67
D A Rauch, P Valiño Ramos, M Khanfar, J Harding, A Joseph, O Griffith, M Griffith, L Ratner
UNLABELLED: Kaposi Sarcoma (KS) is a complex tumor caused by KS-associated herpesvirus 8 (KSHV). Histological analysis reveals a mixture of "spindle cells", vascular-like spaces, extravasated erythrocytes, and immune cells. In order to elucidate the infected and uninfected cell types in KS tumors, we examined skin and blood samples from twelve subjects by single cell RNA sequence analyses. Two populations of KSHV-infected cells were identified, one of which represented a proliferative fraction of lymphatic endothelial cells, and the second represented an angiogenic population of vascular endothelial tip cells...
May 3, 2024: bioRxiv
#68
Andrea Vecchione, Mohsen Khosravi-Maharlooei, Nichole Danzl, Hao Wei Li, Grace Nauman, Rachel Madley, Elizabeth Waffarn, Robert Winchester, Amanda Ruiz, Xiaolan Ding, Georgia Fousteri, Megan Sykes
Human immune system (HIS) mice constructed in various ways are widely used for investigations of human immune responses to pathogens, transplants and immunotherapies. In HIS mice that generate T cells de novo from hematopoietic progenitors, T cell-dependent multisystem autoimmune disease occurs, most rapidly when the human T cells develop in the native NOD.Cg- Prkdc scid Il2rg tm1Wjl (NSG) mouse thymus, where negative selection is abnormal. Disease develops very late when human T cells develop in human fetal thymus grafts, where robust negative selection is observed...
May 5, 2024: bioRxiv
#69
Justin G James, Nora M McCall, Alex I Hsu, Corinna S Oswell, Gregory J Salimando, Malaika Mahmood, Lisa M Wooldridge, Meghan Wachira, Adrienne Jo, Raquel Adaia Sandoval Ortega, Jessica A Wojick, Katherine Beattie, Sofia A Farinas, Samar N Chehimi, Amrith Rodrigues, Lindsay L Ejoh, Blake A Kimmey, Emily Lo, Ghalia Azouz, Jose J Vasquez, Matthew R Banghart, Kate Townsend Creasy, Kevin T Beier, Charu Ramakrishnan, Richard C Crist, Benjamin C Reiner, Karl Deisseroth, Eric A Yttri, Gregory Corder
The anterior cingulate cortex plays a pivotal role in the cognitive and affective aspects of pain perception. Both endogenous and exogenous opioid signaling within the cingulate mitigate cortical nociception, reducing pain unpleasantness. However, the specific functional and molecular identities of cells mediating opioid analgesia in the cingulate remain elusive. Given the complexity of pain as a sensory and emotional experience, and the richness of ethological pain-related behaviors, we developed a standardized, deep-learning platform for deconstructing the behavior dynamics associated with the affective component of pain in mice-LUPE (Light aUtomated Pain Evaluator)...
April 29, 2024: bioRxiv
#70
JOURNAL ARTICLE
Ashwathi Puravankara Menon, Helena Villanueva, Daniel Meraviglia-Crivelli, Hisse M van Santen, Joschka Hellmeier, Angelina Zheleva, Francesca Nonateli, Timo Peters, Tassilo L A Wachsmann, Mercedes Hernandez-Rueda, Johannes B Huppa, Gerhard J Schütz, Eva Sevcsik, Beatriz Moreno, Fernando Pastor
The CD3/T cell receptor (TCR) complex is responsible for antigen-specific pathogen recognition by T cells, and initiates the signaling cascade necessary for activation of effector functions. CD3 agonistic antibodies are commonly used to expand T lymphocytes in a wide range of clinical applications, including in adoptive T cell therapy for cancer patients. A major drawback of expanding T cell populations ex vivo using CD3 agonistic antibodies is that they expand and activate T cells independent of their TCR antigen specificity...
June 11, 2024: Molecular Therapy. Nucleic Acids
#71
REVIEW
Phoomipat Jungcharoen, Kunakorn Thivakorakot, Nachayada Thientanukij, Natkamon Kosachunhanun, Chayanittha Vichapattana, Jutatip Panaampon, Charupong Saengboonmee
Cancer immunotherapy has emerged as a groundbreaking field, offering promising and transformative tools for oncological research and treatment. However, it faces several limitations, including variations in cancer types, dependence on the tumor microenvironments (TMEs), immune cell exhaustion, and adverse reactions. Magnetic nanoparticles, particularly magnetite nanoparticles (MNPs), with established pharmacodynamics and pharmacokinetics for clinical use, hold great promise in this context and are now being explored for therapeutic aims...
2024: Exploration of targeted anti-tumor therapy
#72
REVIEW
Peeranut Winidmanokul, Aussara Panya, Seiji Okada
Cancer continues to be a global health concern, necessitating innovative solutions for treatment. Tri-specific killer engagers (TriKEs) have emerged as a promising class of immunotherapeutic agents, offering a multifaceted approach to cancer treatment. TriKEs simultaneously engage and activate natural killer (NK) cells while specifically targeting cancer cells, representing an outstanding advancement in immunotherapy. This review explores the generation and mechanisms of TriKEs, highlighting their advantages over other immunotherapies and discussing their potential impact on clinical trials and cancer treatment...
2024: Exploration of targeted anti-tumor therapy
#73
REVIEW
James Michael Verner, Harry Frederick Arbuthnott, Raghavskandhan Ramachandran, Manini Bharadwaj, Natasha Chaudhury, Eric Jou
Innate lymphoid cells (ILCs) are the most recently discovered class of innate immune cells found to have prominent roles in various human immune-related pathologies such as infection and autoimmune diseases. However, their role in cancer was largely unclear until recently, where several emerging studies over the past few years unanimously demonstrate ILCs to be critical players in tumour immunity. Being the innate counterpart of T cells, ILCs are potent cytokine producers through which they orchestrate the overall immune response upstream of adaptive immunity thereby modulating T cell function...
2024: Exploration of targeted anti-tumor therapy
#74
Ying Jiang, Dan Feng, Jun Zhu, Daolin Wei, Chuxian Zhao, Huixia Liu, Shan Shao, Chun Wang
Chimeric antigen receptor T cells (CAR T) targeting CD7 for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) showed promising efficacy and safety in some clinical trials. However, most of them were bridged with allogeneic hematopoietic stem cell transplantation (allo-HSCT). We described successful treatment with preventive donor-derived anti-CD7 CAR-T therapy in a case of refractory T lymphoblastic lymphoma following allo-HSCT, who could not receive autologous anti-CD7 CAR-T products due to the low-quality of T lymphocytes...
2024: Frontiers in Immunology
#75
JOURNAL ARTICLE
Johnna F Varghese, Belinda J Kaskow, Felipe von Glehn, Junning Case, Zhenhua Li, Amélie M Julé, Emma Berdan, Shannan Janelle Ho Sui, Yong Hu, Rajesh Krishnan, Tanuja Chitnis, Vijay K Kuchroo, Howard L Weiner, Clare Mary Baecher-Allan
BACKGROUND: Regulatory B cells (Bregs) play a pivotal role in suppressing immune responses, yet there is still a lack of cell surface markers that can rigorously identify them. In mouse models for multiple sclerosis (MS), TIM-1 or TIGIT expression on B cells is required for maintaining self-tolerance and regulating autoimmunity to the central nervous system. Here we investigated the activities of human memory B cells that differentially express TIM-1 and TIGIT to determine their potential regulatory function in healthy donors and patients with relapsing-remitting (RR) MS...
2024: Frontiers in Immunology
#76
JOURNAL ARTICLE
JongHoon Ha, Adam J Grippin, Betty Y S Kim, Wen Jiang
Antibody-based immune checkpoint blockade therapy has revolutionized the field of cancer immunotherapy, yet its efficacy remains limited in immunologically cold tumors. Combining checkpoint inhibitors with costimulatory agonists improves tumoricidal activity of T cells but also can lead to off-target hepatotoxicity. Although bispecific antibodies confer tumor selectivity to alleviate undesirable adverse effects, toxicity concerns persist with increased dosing. In this issue of Cancer Research, Yuwen and colleagues introduce ATG-101, a tetravalent PD-L1×4-1BB bispecific antibody with high programmed death ligand 1 (PD-L1) affinity and low 4-1BB affinity, aiming to mitigate hepatotoxicity...
May 15, 2024: Cancer Research
#77
REVIEW
Yuanbo Pan, Junjie Cheng, Yang Zhu, Jianmin Zhang, Wenpei Fan, Xiaoyuan Chen
Metastasis causes greater than 90% of cancer-associated deaths, presenting huge challenges for detection and efficient treatment of cancer due to its high heterogeneity and widespread dissemination to various organs. Therefore, it is imperative to combat cancer metastasis, which is the key to achieving complete cancer eradication. Immunotherapy as a systemic approach has shown promising potential to combat metastasis. However, current clinical immunotherapies are not effective for all patients or all types of cancer metastases owing to insufficient immune responses...
May 15, 2024: Chemical Society Reviews
#78
JOURNAL ARTICLE
Caroline M Hull, Daniel Larcombe-Young, Roberta Mazza, Molly George, David M Davies, Anna Schurich, John Maher
Interleukin (IL)18 is a potent pro-inflammatory cytokine that is activated upon caspase 1 cleavage of the latent precursor, pro-IL18. Therapeutic T-cell armoring with IL18 promotes autocrine stimulation and positive modulation of the tumor microenvironment (TME). However, existing strategies are imperfect since they involve constitutive/ poorly regulated activity, or fail to modify the TME. Here, we have substituted the caspase 1 cleavage site within pro-IL18 with that preferred by granzyme B, yielding GzB-IL18...
May 14, 2024: Molecular Therapy
#79
JOURNAL ARTICLE
Lukas Egli, Meike Kaulfuss, Juliane Mietz, Arianna Picozzi, Els Verhoeyen, Christian Münz, Obinna Chijioke
BACKGROUND: CAR NK cells as vehicles for engineered "off-the-shelf" cellular cancer immunotherapy have attracted significant interest. Nonetheless, a comprehensive comparative assessment of the anticancer activity of CAR T cells and CAR NK cells carrying approved benchmark anti-CD19 CAR constructs is missing. Here, we report a direct head-to-head comparison of CD19-directed human T and NK cells. METHODS: We generated CAR T and CAR NK cells derived from healthy donor PBMC by retroviral transduction with the same benchmark second-generation anti-CD19 CAR construct, FMC63...
May 14, 2024: Experimental Hematology & Oncology
#80
JOURNAL ARTICLE
Alex C Y Chen, Sneha Jaiswal, Daniela Martinez, Cansu Yerinde, Keely Ji, Velita Miranda, Megan E Fung, Sarah A Weiss, Maria Zschummel, Kazuhiro Taguchi, Christopher S Garris, Thorsten R Mempel, Nir Hacohen, Debattama R Sen
The etiology and effect of age-related immune dysfunction in cancer is not completely understood. Here we show that limited priming of CD8+ T cells in the aged tumor microenvironment (TME) outweighs cell-intrinsic defects in limiting tumor control. Increased tumor growth in aging is associated with reduced CD8+ T cell infiltration and function. Transfer of T cells from young mice does not restore tumor control in aged mice owing to rapid induction of T cell dysfunction. Cell-extrinsic signals in the aged TME drive a tumor-infiltrating age-associated dysfunctional (TTAD ) cell state that is functionally, transcriptionally and epigenetically distinct from canonical T cell exhaustion...
May 14, 2024: Nature Immunology
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