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214 results for “Preclinical models”
Deciphering the scopolamine rat model by preclinical functional MRI
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Modulation of the tumour promoting functions of cancer associated fibroblasts by phosphodiesterase type 5 inhibition increases the efficacy of chemotherapy in human preclinical models of esophageal adenocarcinoma
<p>These are whole-slide digital pathology images of esophageal adenocarcinoma (EAC) patient-derived xenograft models. EAC biopsy specimens were cultured <em>in vitro</em> before implanting into immuno-deficient mice. Mice were then divided into the following treatment groups and treated with combinations of chemotherapy and PDE5 inhibitors as follows:</p> <ol> <li>Untreated</li> <li>Epirubicin + Cisplatin + Capecitabine (ECX)</li> <li>ECX + Vardenafil</li> <li>ECX + Tadalafil</li> </ol> <p>All whole slide images are in Olympus .vsi format and can be opened using the BioFormats library in QuPath. We have also included classifiers and scripts for performing the digital pathology analysis in QuPath, and information to link each mouse with treatment groups and corresponding whole slide images.</p> <p>File metadata:</p> <p>classifiers.zip - Folder containing pixel classifiers used for segmentation of IHC stains. These classifiers are to be important into QuPath for the respective analysis of Periostin (POSTN) and alpha Smooth Muscle Actin (SMA) staining using the included Groovy scripts in the scripts folder.</p> <p>SMA.zip - Folder containing whole slide images of mouse patient-derived xenograft tumours in .vsi format (Olympus VS110). Immunohistochemistry with anti-alpha Smooth Muscle Actin antibody.<br> POSTN.zip - Folder containing whole slide images of mouse patient-derived xenograft tumours in .vsi format (Olympus VS110). Immunohistochemistry with anti-Periostin antibody.</p> <p>scripts.zip - Folder containing all groovy scripts used in QuPath for tissue detection (Whole Section Tissue Detection.groovy), and segmentation of POSTN (POSTN Quantification Mice.groovy) and SMA staining tissue areas (SMA Quantification Mice.groovy).</p> <p>POSTN.xlsx - Data on the mice for which anti-POSTN IHC is available. Column names as follows:<br> Image: file name (corresponding to .vsi file).<br> Mouse_ID: Mouse identifier.<br> Treatment: Treatment administered. ECX - Epirubicin, Cisplatin and Capecitabine.<br> POSTN_Area: Total measured area of POSTN+ tissue in the tissue section (in um^2).<br> Total_Area: Total area of the tissue section (in um^2).<br> percentage_POSTN: Percentage of total tissue area that is stained with POSTN (%).</p> <p>SMA.xlsx - Data on the mice for which anti-SMA IHC is available. Column names as follows:<br> Image: file name (corresponding to .vsi file).<br> Mouse_ID: Mouse identifier.<br> Treatment: Treatment administered. ECX - Epirubicin, Cisplatin and Capecitabine.<br> SMA_Area: Total measured area of SMA+ tissue in the tissue section (in um^2).<br> Total_Area: Total area of the tissue section (in um^2).<br> percentage_SMA: Percentage of total tissue area that is stained with SMA (%).</p>
Identification of a small molecule Tim-3 inhibitor to potentiate T cell-mediated antitumor immunotherapy in preclinical models
<p><span>T cell immunoglobulin and mucin-containing molecule 3 (Tim-3), expressed in dysfunctional and exhausted T cells, has been widely acknowledged as a promising immune checkpoint target for tumor immunotherapy. Here, using a strategy combining virtual and functional screening, we identified a compound named ML-T7 that targets the FG-CC' cleft of Tim-3, a highly conserved binding site of </span><span>phosphatidylserine</span><span> (PtdSer) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). ML-T7 enhanced the survival and antitumor activity of </span><span>primary CD8<sup>+</sup> cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells and reduced their exhaustion </span><span>in vitro and in vivo</span><span>. In addition, ML-T7 promoted NK cells' killing activity and DC antigen-presenting capacity, consistent with the reported activity of Tim-3.</span><span> Notably, ML-T7 strengthened DCs' functions through both Tim-3 and Tim-4, consistent with the hypothesis that Tim-4 contains a similar FG-CC' loop. Intraperitoneal dosing of ML-T7 showed comparable tumor inhibitory effects to Tim-3 blocking antibody. ML-T7 reduced syngeneic tumor progression in both wildtype and Tim-3 humanized mice and alleviated the immunosuppressive microenvironment. Furthermore, combined ML-T7 and anti-PD-1 therapy had greater therapeutic efficacy than monotherapy in mice, supporting further development of ML-T7 for tumor immunotherapy. Our study demonstrates a potential small molecule for selectively blocking Tim-3 and warrants further study.</span></p>
Behavioral data for: A preclinical model of THC edibles that produces high-dose cannabimimetic responses
<p>No preclinical experimental approach enables the study of voluntary oral consumption of high-concentration Δ<sup>9</sup>-tetrahydrocannabinol (THC) and its intoxicating effects, mainly owing to the aversive response of rodents to THC that limits intake. Here we developed a palatable THC formulation and an optimized access paradigm in mice to drive voluntary consumption.<strong> </strong>THC was formulated in chocolate gelatin (THC-E-gel). Adult male and female mice were allowed <em>ad libitum </em>access for 1 and 2 h. Cannabimimetic responses (hypolocomotion, analgesia, and hypothermia) were measured following access. Levels of THC and its metabolites were measured in blood and brain tissue. Acute acoustic startle responses were measured to investigate THC-induced psychotomimetic behavior. When allowed access for 2 h to THC-E-gel on the second day of a three-day exposure paradigm, adult mice consumed up to ≈30 mg/kg over 2 h which resulted in robust cannabimimetic behavioral responses (hypolocomotion, analgesia and hypothermia). Consumption of the same gelatin decreased on the following 3<sup>rd</sup> day of exposure. Pharmacokinetic analysis show that THC-E-gel consumption led to parallel accumulation of THC and its psychoactive metabolite, 11-OH-THC, in brain, a profile that contrasts with the known rapid decline in brain 11-OH-THC levels following THC intraperitoneal (<em>i.p</em>.) injections. THC-E-gel consumption increased the acoustic startle response in males but not in females, demonstrating a sex-dependent effect of consumption. Thus, while voluntary consumption of THC-E-gel triggered equivalent cannabimimetic responses in male and female mice, it potentiated acoustic startle responses preferentially in males. We build a dose-prediction model that included cannabimimetic behavioral responses elicited by <em>i.p.</em> versus THC-E-gel to test the accuracy and generalizability of this experimental approach and found that it closely predicted the measured acoustic startle results in males and females. In summary, THC-E-gel offers a robust preclinical experimental approach to study cannabimimetic responses triggered by voluntary consumption in mice, including sex-dependent psychotomimetic responses.</p>
mRNA prime–boost evolves precursors toward VRC01-like broadly neutralizing antibodies in preclinical humanized mouse models
<p>Germline-targeting (GT) protein immunogens to induce VRC01-class broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) of the HIV Envelope have shown promise in clinical trials. Here, we preclinically validated the mRNA-LNP delivery of one such immunogen, eOD-GT8, as a soluble self-assembling 60mer nanoparticle in humanized mouse models. In a model with three humanized B cell lineages bearing distinct VRC01-precursor B cell receptors (BCRs) with similar affinities for eOD-GT8, all lineages could be simultaneously primed and undergo diversification and affinity maturation with no sign of exclusionary competition. Boosts drove precursor B cell participation in germinal centers, the accumulation of somatic hypermutations, including in key VRC01-class positions, and affinity maturation to boost and native-like antigens in two of the three precursor lineages. We have preclinically validated a prime-boost regimen of soluble self-assembling nanoparticles delivered by mRNA-LNP, demonstrating that multiple lineages can be primed, boosted, and diversify along the bnAb pathway.</p>
Payload-delivering engineered γδ T cells display enhanced cytotoxicity, persistence, and efficacy in preclinical models of osteosarcoma
<p>T cell-based cancer immunotherapy has typically relied on membrane-bound cytotoxicity enhancers such as chimeric antigen receptors expressed in autologous αβ T cells. These approaches are limited by tonic signaling of synthetic constructs and costs associated with manufacturing. γδ T cells are an emerging alternative for cellular therapy, possessing innate anti-tumor activity, potent antibody-dependent cellular cytotoxicity, and minimal alloreactivity. We present an immunotherapeutic platform technology built around the innate properties of the Vγ9Vδ2 T cell, harnessing specific characteristics of this cell type and offering an allo-compatible cellular therapy that recruits bystander immunity. We engineered γδ T cells to secrete synthetic tumor-targeting opsonins in the form of an scFv-Fc fusion protein and a mitogenic IL-15Ra–IL-15 fusion protein (stIL15). Using GD2 as a model antigen, we show that GD2-specific opsonin-secreting Vγ9Vδ2 T cells (stIL15-OPS-γδ T cells) have enhanced cytotoxicity and promote bystander activity of other lymphoid and myeloid cells. Secretion of stIL-15 abrogated the need for exogenous cytokine supplementation and further mediated activation of bystander natural killer cells. Compared to unmodified γδ T cells, stIL15-OPS-γδ T cells exhibited superior in vivo control of subcutaneous tumors and persistence in the blood. Moreover, stIL15-OPS-γδ T cells were efficacious against patient-derived osteosarcomas in animal models and in vitro, where efficacy could be boosted with the addition of zoledronic acid. Together the data identify stIL15-OPS-γδ T cells as a candidate allogeneic cell therapy platform combining direct cytolysis with bystander activation to promote tumor control.</p>
Behavioral data for: A preclinical model of THC edibles that produces high-dose cannabimimetic responses
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Identification of a small molecule Tim-3 inhibitor to potentiate T cell-mediated antitumor immunotherapy in preclinical models
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Targeted inhibition of kisspeptin neurons reverses hyperandrogenemia and abnormal hyperactive LH secretion in a preclinical mouse model of polycystic ovary syndrome
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Payload-delivering engineered γδ T cells display enhanced cytotoxicity, persistence, and efficacy in preclinical models of osteosarcoma
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mRNA prime–boost evolves precursors toward VRC01-like broadly neutralizing antibodies in preclinical humanized mouse models
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Dataset for: Therapeutic potential of extracellular vesicles in preclinical stroke models: a systematic review and meta-analysis
<p>This upload contains the data extracted from studies included in our meta-analysis entitled "Therapeutic potential of extracellular vesicles in preclinical stroke models: a systematic review and meta-analysis". It also contains the code used to perform the meta-analysis and generate the figures in the publication in R. </p>
Dataset related to article "Intracerebral Injection of Extracellular Vesicles from Mesenchymal Stem Cells Exerts Reduced Aβ Plaque Burden in Early Stages of a Preclinical Model of Alzheimer's Disease."
<p>Bone marrow Mesenchymal Stem Cells (BM-MSCs), due to their strong protective and anti-inflammatory abilities, have been widely investigated in the context of several diseases for their possible therapeutic role, based on the release of a highly proactive secretome composed of soluble factors and Extracellular Vesicles (EVs). BM-MSC-EVs, in particular, convey many of the beneficial features of parental cells, including direct and indirect β-amyloid degrading-activities, immunoregulatory and neurotrophic abilities. Therefore, EVs represent an extremely attractive tool for therapeutic purposes in neurodegenerative diseases, including Alzheimer's disease (AD). We examined the therapeutic potential of BM-MSC-EVs injected intracerebrally into the neocortex of APPswe/PS1dE9 AD mice at 3 and 5 months of age, a time window in which the cognitive behavioral phenotype is not yet detectable or has just started to appear. We demonstrate that BM-MSC-EVs are effective at reducing the Aβ plaque burden and the amount of dystrophic neurites in both the cortex and hippocampus. The presence of Neprilysin on BM-MSC-EVs, opens the possibility of a direct β-amyloid degrading action. Our results indicate a potential role for BM-MSC-EVs already in the early stages of AD, suggesting the possibility of intervening before overt clinical manifestations.</p>
Establish Diagnostic and Prognostic Models for Preclinical AD Patients Based on Multimodal MRI, Behavioral, Genetic, and Plasma Biomarkers
ClinicalTrials.gov study NCT06561906. IPD Sharing: UNDECIDED. Countries: 1. Publications: 1.
Next pErsonalized Cancer tX With mulTi-omics and Preclinical Model
ClinicalTrials.gov study NCT02141152. IPD Sharing: Not stated. Countries: 1. Publications: 1.
New Models for the Evaluation of Preclinical Treatment for Urothelial Carcinomas of the Upper Excretory Tract.
ClinicalTrials.gov study NCT04944550. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Peripheral mononuclear blood cell apheresis in a preclinical ovine model
<p>Dataset relating to sheep blood values</p>
Dataset related to "Translational approach to assess brain injury after cardiac arrest in preclinical models: a narrative review"
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Synthesis and preclinical evaluation of a novel fluorine-18 labeled small-molecule PET radiotracer for imaging of CXCR3 receptor in mouse models of atherosclerosis
<p>Background CXCR3 is a chemokine receptor and is expressed in innate and adaptive immune cells. It promotes<br> the recruitment of T-lymphocytes and other immune cells to the inflammatory site in response to the binding of cognate<br> chemokines. Upregulation of CXCR3 and its chemokines has been found during atherosclerotic lesion formation.<br> Therefore, detection of CXCR3 by positron emission tomography (PET) radiotracer can be a useful tool for detecting the development of atherosclerosis in a noninvasive manner. Herein, we report the synthesis, radiosynthesis, and characterization of a novel fluorine-18 (F-18, <sup>18</sup>F) labeled small-molecule radiotracer for the imaging of the CXCR3 receptor in mouse models of atherosclerosis.<br> Results The reference standard <strong>1</strong> and its precursor <strong>9</strong> were synthesized over 5 steps from starting materials in good to moderate yields. The measured K<sub>i</sub> values of CXCR3A and CXCR3B were 0.81 ± 0.02 nM and 0.31 ± 0.02 nM, respectively. [<sup>18</sup>F]<strong>1</strong> was prepared by a two-step radiosynthesis with a decay-corrected radiochemical yield of 13 ± 2%, radiochemical purity > 99%, and specific activity of 44.4 ± 3.7 GBq/μmol at the end of synthesis (n = 6). The baseline studies showed that [<sup>18</sup>F]<strong>1</strong> displayed high uptake in the atherosclerotic aorta and brown adipose tissue in Apolipoprotein E (ApoE) knockout (KO) mice fed with a high-fat diet over 12 weeks. The uptake of [<sup>18</sup>F]<strong>1</strong> in these regions was reduced significantly in self-blocking studies, demonstrating CXCR3 binding specificity. Contrary to this, no significant differences in uptake of [<sup>18</sup>F]<strong>1</strong> in the abdominal aorta of C57BL/6 control mice fed with a normal diet were observed in both baseline and blocking studies, indicating increased CXCR3 expression in atherosclerotic lesions. Immunohistochemistry studies demonstrated that [<sup>18</sup>F]<strong>1</strong>-positive regions were correlated with CXCR3 expression, but some<br> atherosclerotic plaques with significant size were not detected by [<sup>18</sup>F]<strong>1</strong>, and their CXCR3 expressions were minimal.<br> Conclusion [<sup>18</sup>F]<strong>1</strong> was synthesized with good radiochemical yield and high radiochemical purity. In PET imaging<br> studies, [<sup>18</sup>F]<strong>1</strong> displayed CXCR3-specific uptake in the atherosclerotic aorta in ApoE KO mice. [<sup>18</sup>F]<strong>1</strong> visualized CXCR3<br> expression in different regions in mice aligned with the tissue histology studies. Taken together, [<sup>18</sup>F]<strong>1</strong> is a potential<br> PET radiotracer for imaging CXCR3 in atherosclerosis.</p>
Neurobehavioral Signatures of Sign- and Goal-Tracking in Emerging Adults: Translation of a Preclinical Model
ClinicalTrials.gov study NCT07094061. IPD Sharing: YES. Countries: 1. Publications: 0.
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These curated guides explain access requirements, typical timelines, costs, and reuse considerations for widely used research datasets.
Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.