The increasing human population, combined with low inefficiency and adverse effects of available pesticides, has magnified the urgent need of developing next-generation pesticides. Among the available approaches, strategies targeting invertebrate G protein-coupled receptors (GPCRs) are very promising as these receptors are the targets of endogenous neuropeptides/neuromodulators that upon binding to their receptors induce profound changes in insect physiology. Therefore, exploring GPCR regulators has great potential in the development of targeted next-generation pesticides. Despite the great potential of such alternative pesticides, so far there has been only one approved compound, Amitraz, which conveys its antipest activity via the GPCR Octopamine receptor. Here, we review the current status of pesticide development, hazards associated with conventional pesticide compounds, alternative strategies that involve next-generation of pesticides, structural features of GPCRs, and opportunities and challenges of targeting the members of this superfamily in invertebrates to develop anti-pest agents. In conclusion, we emphasize that the potential of GPCRs cannot be utilized in full without more genomic and transcriptomic data to improve our understanding of the complex network of peptidergic signaling pathways. We argue how vital it is to obtain three-dimensional (3D) structural data on physiologically important target GPCRs and encourage the readers to use the state of the art in silico methods such as virtual screening for the discovery of new pesticide compounds.
Application of heat above 43°C and up to 47°C, the so-called “thermal ablation” range, leads to tumor cell destruction either by apoptosis or by necrosis. However, tumor cells have developed mechanisms of defense that render them thermoresistant. Of importance, the in situ application of heat for the treatment of localized solid tumors can also prime specific antitumor immunity. Herein, a bioinformatic approach was employed for the identification of molecular determinants implicated in thermoresistance and immunogenic cell death (ICD). To this end, both literature-derived (text mining) and microarray gene expression profile data were processed, followed by functional enrichment analysis. Two important functional gene modules were detected in hyperthermia resistance and ICD, the former including members of the heat shock protein (HSP) family of molecular chaperones and the latter including immune-related molecules, respectively. Of note, the molecules HSP90AA1 and HSPA4 were found common between thermoresistance and damage signaling molecules (damage-associated molecular patterns (DAMPs)) and ICD. In addition, the prognostic potential of HSP90AA1 and HSPA4 overexpression for cancer patients' overall survival was investigated. The results of this study could constitute the basis for the strategic development of more efficient and personalized therapeutic strategies against cancer by means of thermotherapy, by taking into consideration the genetic profile of each patient.
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