Introduction: Opioid Use Disorder (OUD) is a chronic neuropsychiatric condition driven by persistent neuroadaptive changes in reward, motivation, and stress-related circuits. While opioid receptors are central to OUD, the broader role of G protein-coupled receptors (GPCRs) in opioid-induced neuroplasticity remains underexplored. This study systematically characterizes GPCR dysregulation in OUD to identify potential pharmacological targets. Methods: We performed transcriptomic analysis of RNA sequencing (RNA-seq) datasets from addiction-related brain regions, including the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (GSE174409), Brodmann area 9 (GSE182321), and central amygdala (GSE194368). A curated set of ~900 GPCR genes was analyzed for differentially expressed genes (DEG), principal component analysis (PCA), and hierarchical clustering. Drug-targetable GPCRs were identified via DrugBank and ChEMBL, and their behavioral and stress-related roles were determined. Protein-protein interaction (PPI) networks were constructed using STRING. Results: We identified 58 GPCRs consistently dysregulated across brain regions, reflecting common molecular adaptations in OUD. PCA revealed a clear separation between OUD and control groups, indicating distinct receptor remodeling. Hierarchical clustering identified functional subgroups, including drug-targetable GPCRs and orphan GPCRs. Notably, 17 GPCRs—including DRD1, DRD3, DRD4, HTR1A, HTR2A, OXTR, and CNR1—are involved in behavioral regulation and addiction vulnerability. Network analysis highlighted key receptor hubs, suggesting novel therapeutic targets. Conclusion: The present study provides a receptor-centric framework for drug repurposing and precision medicine in OUD. Integrating transcriptomic and pharmacological data, we highlight GPCRs with translational potential. Further validation through functional assays and single-cell studies is warranted.

Background: Liver cancer (LC) is among the most common and fatal cancers worldwide. A four-fold increasing trend is reported for LC age-standardized mortality rate (ASMR) in Iran within 1990– 2015. In the present study, we aimed to report the incidence rate of LC during the 13-year establishment of the Golestan population-based cancer registry (GPCR). Methods: Age-standardized incidence rate (ASIR) per 100 000 person-years was calculated using CanReg5 software. The Joint point regression analysis was used to assess the temporal trends in incidence rate of LC. Results: During the study period, GPCR registered 575 of LC cases, of which 373 (64. 9%) were men and 297 (51. 6%) lived in rural areas. The mean (SD) age of LC in men and women were 60. 3 (17. 2) and 58. 0 (17. 1), respectively. The ASIR of LC was significantly higher in men than women (4. 7 vs. 2. 6; P value < 0. 01) and a minimal increasing trend in LC incidence was observed in both sexes. The incidence rate of LC was significantly higher in rural areas compared to the urbans (3. 91 vs. 3. 40; P value = 0. 04). In the last 13 years, rural population had a significant increasing trend in ASIR of LC (average annual percent change [AAPC] = 7. 85, P value = 0. 005). Conclusion: LC was more prevalent in men among both urban and rural populations. The results showed a significant increasing trend in rural areas that requires Golestan health care system to take action in controlling the burden of LC in rural areas.

A growing body of evidence suggests that GPCRs exist and function as dimers or higher oligomers. The evidence for GPCR dimerization comes from biochemical, biophysical and functional studies. In addition, researchers have shown the occurrence of heterodimerization between different members of the GPCR family. Two receptors can interact with each other to make a dimer through their extracellular loops, transmembrane helices and intracellular loops. The nature of bonds between two receptors can vary from covalent (e.g. disulphide bonds) to non-covalent (for instance hydrophobic interactions between trans-membrane helices or coiled coil structures) or a combination of both. Dimerization can occur in and affect different stages of a receptor’s life, namely trafficking, signaling and internalization, and can be seen as the natural way to regulate receptor activity or increase the functional repertoire of proteins. Different structures for GPCR dimers have been proposed, for example a simple contact dimer or an interlocking domain-swapped structure. Here we introduce some of the information available on GPCR dimerization, which includes early studies that had been dismissed until the relatively recent past and some of the more recent data which has vindicated these early studies.

G protein-coupled receptor (GPCR), superfamily of heptahelical transmembrane receptor proteins, controls a plethora of signals through either interaction with G protein heterotrimer or independent of G protein. Unlike animals possessing a considerable number of canonical GPCRs and their cognate heterotrimeric G-protein components for signal perception and transduction, plants have a relatively simple repertoire of G proteins. Although the functional cooperativity of plant G-proteins with heptahelical transmembrane receptor-like proteins as Arabidopsis Regulators of G Protein Signalling (RGS1) is established, the presence of canonical GPCR is arguable. However, genome duplication events and polyploidy levels in several plants suggest the presence of several heptahelical transmembrane receptor-like proteins with analogous biochemical features. A high degree of sequence diversity and limited proteome data pose major bottlenecks associated with the identification of GPCR(s). We have identified eight, three, one, and three canonical GPCR-like proteins in Arabidopsis thaliana, Glycine max, Sorghum bicolor, and Zea mays, respectively. Similarly, we have also identified 25 (At:3, Gm:13, Sb:3, and Zm:6) uncanonical GPCR-like proteins that do not interact with G protein α subunit (Gα) but are analogous to various GPCRs of different signalling pathways. Identified high probability GPCR-like plant proteins have all signature motifs and functional characteristic features of the canonical GPCR. Current findings provide an insight into the diversity, distribution, and conservation of candidate GPCRs in plants.

Background: The use of deep fried oils (DFOs) to cook foods is associated with numerous diseases. Although the role of physical activity and some supplements on fat lipolysis has been established, the effect of aerobic training (AT) and octopamine (Oct) on octopamine receptor-dependent lipolysis pathway is not well understood. Objectives: The present study aimed to investigate the effect of AT and Oct supplementation on the expression of Oct receptors in the visceral adipose tissue of DFO-exposed rats. Methods: In this experimental study, 30 male Wistar rats were divided into (1) healthy control (C), (2) DFO, (3) DFO + Oct, (4) DFO + AT, and (5) DFO + Oct + AT groups. Aerobic training was performed for four weeks, five sessions per week at an intensity of 16-26 m/min and equivalent to 50%-65% VO2max, and Otc supplement was interperitoneally injected at 81  mol/kg five days a week. Results: Aerobic training and Oct supplementation increased tyramin-R and hormone-sensitive lipase (HSL) (P 0. 05), while Oct significantly decreased G protein-coupled receptors (GPCR) (P  0. 05). Also, the interaction of AT and Oct on GPCR reduction was significant (P 0. 05). Conclusions: It seems that AT and Otc alone improve octopamine receptors and lipolysis markers in the visceral adipose tissue of DFO-treated rats, but these two factors have no interactive effects on this pathway.