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Message: Undefined array key "choices"
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Message: strpos(): Passing null to parameter #1 ($haystack) of type string is deprecated
Filename: models/Detail_model.php
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File: /var/www/html/application/models/Detail_model.php
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Function: strpos
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Function: insertAPISummary
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File: /var/www/html/application/helpers/my_audit_helper.php
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Function: str_replace
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Function: formatAIDetailSummary
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Filename: controllers/Detail.php
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File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Recombinant adeno-associated viruses (rAAVs) serve as vectors for in vivo gene delivery in both mice and humans, and have broad applicability for the treatment of genetic diseases. Clinical trials with AAV vectors have demonstrated promise and safety in several human diseases. However, the in vivo validation of novel AAV constructs expressing products that act specifically on human cells and tissues is limited by a paucity of effective translatable models. Humanized mice that are engrafted with human cells, tissues, and immune systems offer strong potential to test the biological effectiveness of AAV vectors on human cells and tissues. Using the BLT (bone marrow, liver, thymus) humanized NOD-scid Il2rg (NSG) mouse model, which enables efficient development of HLA-restricted effector and regulatory T cells (Tregs), we have evaluated the delivery and function of human interleukin (IL)-2 by an AAV vector. Humanized mice treated with an AAV vector expressing human IL-2 showed a significant and sustained increase in the number of functional human FOXP3CD4 Tregs. The expression of human IL-2 did not significantly change the levels or activation status of conventional T-cell subsets. Numbers of activated human natural killer cells were also increased significantly in humanized mice treated with the IL-2 vector. These data recapitulate observations in clinical trials of IL-2 therapy and collectively show that humanized mouse models offer a translational platform for testing the efficacy of AAV vectors targeting human immune cells.
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http://dx.doi.org/10.1089/hum.2017.072 | DOI Listing |
Front Immunol
December 2024
SinoMab BioScience Limited, Hong Kong, Hong Kong SAR, China.
Background: Alarmins mediate type 2 T helper cell (Th2) inflammation and serve as upstream signaling elements in allergic inflammation and autoimmune responses. The alarmin interleukin (IL)-25 binds to a multi-domain receptor consisting of IL-17RA and IL-17RB subunits, resulting in the release of Th2 cytokines IL-4, IL-5, IL-9 and IL-13 to drive an inflammatory response. Therefore, the blockage of IL-17RB via SM17, a novel humanized monoclonal antibody, offers an attractive therapeutic target for Th2-mediated diseases, such as asthma.
View Article and Find Full Text PDFGenes Immun
December 2024
Department of Hepatobiliary Surgery, Municipal Hospital Affiliated to Taizhou University, Taizhou, China.
The hypoxic microenvironment is an essential feature of solid tumors. Autophagy has been controversial in its role in immune regulation. This project aims to elucidate the impact of autophagy in pancreatic cancer (PC) under specific conditions (hypoxia) on CD8 T cells and the regulatory mechanisms behind it.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
December 2024
Department of Oncology, Molecular Biotechnology Center "G. Tarone", University of Torino, Piazza Nizza 44, Torino, 10126, Italy.
Background: Malignant pleural mesothelioma (MPM) is a highly chemo-refractory and immune-evasive tumor that presents a median overall survival of 12-14 months when treated with chemotherapy and immunotherapy. New anti-tumor therapies as well as the concomitant reactivation of immune destruction are urgently needed to treat patients with this tumor. The aim of this work is to investigate the potential effect of ecteinascidin derivatives as lurbinectedin as new first-line treatment option in MPM, alone and in combination with immunotherapy.
View Article and Find Full Text PDFCell Tissue Res
December 2024
Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Blastocyst complementation can potentially generate a rodent model with humanized nasopharyngeal epithelium (NE) that supports sustained Epstein-Barr virus (EBV) infection, enabling comprehensive studies of EBV biology in nasopharyngeal carcinoma. However, during this process, the specific gene knockouts required to establish a developmental niche for NE remain unclear. We performed bioinformatics analyses and generated Foxa1 mutant mice to confirm that Foxa1 disruption could potentially create a developmental niche for NE.
View Article and Find Full Text PDFJ Virol
December 2024
State Key Laboratory for Animal Disease Control and Prevention & National Data Center for Animal Infectious Diseases, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.
Neutralizing antibodies (nAbs) are important for the treatment of emerging viral diseases and for effective vaccine development. In this study, we generated and evaluated three nAbs (1H9, 2D7, and C4H4) against H7N9 influenza viruses and found that they differ in their ability to inhibit viral attachment, membrane fusion, and egress. We resolved the cryo-electron microscopy (cryo-EM) structures of H7N9 hemagglutinin (HA) alone and in complex with the nAb antigen-binding fragments (Fabs) and identified the HA head-located epitope for each nAb, thereby revealing the molecular basis and key residues that determine the differences in these nAbs in neutralizing H7N9 viruses.
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