Ontology highlight
ABSTRACT:
PROVIDER: PRJNA819108 | ENA |
REPOSITORIES: ENA
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Project description:Nanoparticles-mediated TRPV1 channel blockade amplifies cancer thermo-immunotherapy via heat shock factor 1 modulation
| PRJNA819268 | ENA
Project description:Survival of malignant tumours is highly relevant to their intrinsic self-defense pathways such as heat shock protein (HSP) during cancer therapy, yet precisely dismantling self-defenses to amplify antitumour potency remains unexplored. Herein, we demonstrate that nanoparticles-mediated transient receptor potential vanilloid member 1 (TRPV1) channel blockade selectively modulates heat shock factor 1 to suppress dual self-defense pathways for potentiating thermo-immunotherapy. TRPV1 blockade is identified to inhibit calcium influx and subsequent nuclear translocation of HSF1 upon hyperthermia, leading to selective suppression of stressfully overexpressed HSP70 for enhancing thermotherapeutic efficacy against a variety of primary, metastatic and recurrent tumours. Particularly, the suppression of HSF1 translocation further restrains TGFβ pathway to apparently degrade extracellular matrix in tumour for improving the infiltration of antitumour therapeutics and immune cells into highly fibrotic and immunosuppressive pancreatic cancers, ultimately synergizing with anti-PD-L1 antibody to retrieve thermo-immunotherapy with tumour-eradicable and immune memory effects. The nanoparticles-mediated TRPV1 blockade represents as an effective and universal approach to selectively dismantle self-defenses for potent cancer therapy.
2022-03-24 | GSE199299 | GEO
Project description:We developed an approach to rapidly eliminate the subgroup of sensory neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia using agonist treatment followed by density centrifugation. To identify transcripts predomintly expressed in TRPV1-positive neurons, we compared the transcriptome of all cells within sensory ganglia versus all cells without TRPV1 expressing neurons using RNA-Seq.
2015-05-12 | GSE59727 | GEO
Project description:We developed an approach to rapidly eliminate the subgroup of sensory neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia using agonist treatment followed by density centrifugation. To identify transcripts predominantly expressed in TRPV1-positive neurons, we compared the transcriptome of all cells within sensory ganglia versus all cells without TRPV1 expressing neurons using RNA-Seq.
2015-12-30 | E-MTAB-2789 | biostudies-arrayexpress
Project description:Vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species or cell type specific manner. In each case, robust thermal sensitivity likely reflects specialized anatomical features of infrared sensing pit organs, as well as intrinsic heat sensitivity of trigeminal nerve fibers that innervate these structures. Here we show that vampire bats use a molecular strategy involving alternative splicing of the TRPV1 gene to generate a channel specifically within trigeminal ganglia that has a reduced thermal activation threshold. Selective expression of splicing factors in trigeminal, but not dorsal root ganglia, together with unique organization of the vampire bat TRPV1 gene underlies this mechanism of sensory adaptation. Comparative genomic analysis of the TRPV1 locus supports phylogenetic relationships within the proposed Pegasoferae clade of mammals. Gene expression measurements implicate a TRPV1 splice isoform as the heat-sensitive channel in vampire bats
2011-08-04 | E-GEOD-28243 | biostudies-arrayexpress
Project description:We developed an approach to rapidly eliminate the subgroup of sensory neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia using agonist treatment followed by density centrifugation. To identify transcripts predomintly expressed in TRPV1-positive neurons, we compared the transcriptome of all cells within sensory ganglia versus all cells without TRPV1 expressing neurons using RNA-Seq. Four replicate experiments with RNA from DRG neurons of one rat per experiment were performed. Dissociated neurons were split up in three parts, treated with solvent DMSO (0.1%), casaicin (10 µM), or RTX (100 nM) for 30 min followed by gradient centrifugation. RNA was extracted from the remaining pellet containing either all cells or all cells without TRPV1-positive neurons.
2015-05-12 | E-GEOD-59727 | biostudies-arrayexpress
Project description:Previous studies have shown the increased thermo-tolerance of pathogenic bacteria if pre-exposed to temperatures above their optimal levels prior to a particular heat treatment. It was unclear, however, whether there was a direct relationship between the different gene expression and the induced thermo-tolerance. Microarray analysis was performed to identify the differentially expressed genes during heat stress by comparing the transcriptome of L. monocytogenes under optimal temperature (37°C), and thermo-tolerance inducing (48°C for 30 minutes. A majority of the differentially expressed genes were up-regulated at heat shock as compared to those that were down-regulated when the cells were exposed to thermo-tolerance inducing conditions. Though many of the differentially expressed genes could be tentatively classified based on the current functional classification of genes (COG) per the NCBI database, many of the gene loci could not been attributed to a specific function due to the current limited knowledge on the functional genomics of L. monocytogenes.
2020-12-31 | GSE26570 | GEO
Project description:Vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species or cell type specific manner. In each case, robust thermal sensitivity likely reflects specialized anatomical features of infrared sensing pit organs, as well as intrinsic heat sensitivity of trigeminal nerve fibers that innervate these structures. Here we show that vampire bats use a molecular strategy involving alternative splicing of the TRPV1 gene to generate a channel specifically within trigeminal ganglia that has a reduced thermal activation threshold. Selective expression of splicing factors in trigeminal, but not dorsal root ganglia, together with unique organization of the vampire bat TRPV1 gene underlies this mechanism of sensory adaptation. Comparative genomic analysis of the TRPV1 locus supports phylogenetic relationships within the proposed Pegasoferae clade of mammals.
2011-08-04 | GSE28243 | GEO
Project description:We compared transcriptomic changes, 5'-triphosphorylated (TSS) and 5'-monophosphorylated (PSS) RNA ends of a thermo-sensitive and a wild-typic RNase E mutant strain of the cyanobacterium Synechocystis sp. PCC6803 (rne(Ts) and rne(WT)) before and after a heat shock. Analysis of changing 5'-monophosphorylated ends revealed RNase E depedent processing sites on a transcriptome-wide level.
2021-07-30 | GSE180316 | GEO
Project description:Given the inaccessibility of human sensory neurons (SNs), it is yet to be established whether the signalling pathway between histamine 1 receptor (H1R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) is conserved between humans and mammalian models. Accessible human SNs are vital for identifying TRPV1 antagonists with higher potential for success in clinical trials targeting histaminergic itch, especially given TRPV1's species specificity concerns. Hence to build a humanized histamine-dependent itch model, we derived peripheral sensory neurons from human pluripotent stem cells (hiPSC-SNs) and validated channel functionality using immunostaining, calcium imaging and multielectrode array (MEA) recordings. Here, we demonstrated that a subset of hiPSC-SNs exhibits co-expression of H1R and TRPV1, responding to both histamine and capsaicin agonists. We found that inhibiting TRPV1 prevented histamine activation. Moreover, we show that silencing histamine-sensitive neurons reduces capsaicin response, and silencing capsaicin-sensitive neurons diminishes histamine response. To assess the ability of hiPSC-SNs in TRPV1 antagonist drug screening, we evaluated two well-established hyperthermic and three thermal-neutral TRPV1 antagonists. Our finding identifies SB366791, a thermal-neutral antagonist, as a potent inhibitor of H1R activation. The use of hiPSC-SNs may therefore provide a physiologically relevant means to perform large-scale screening to discover anti-pruritic agents predictive of actual efficacy in human clinical trials.
2024-02-27 | GSE256435 | GEO