Daegu Haany University

Abstract To date, no pharmacotherapy has been approved for cocaine use disorder. Endocannabinoid signaling is closely related to dopamine-dependent reinforcement and may regulate cocaine-related behaviors. In this study, we used common marmosets ( Callithrix jacchus ) to investigate whether 2-arachidonoylglycerol (2-AG), an endogenous cannabinoid lipid, reduces cocaine reinforcement in a non-restraint oral self-administration model. Marmosets performed oral cocaine self-administration under a fixed-ratio 1 schedule, and cocaine intake was confirmed using plasma benzoylecgonine detection. Dopamine transporter (DAT)-related positron emission tomography (PET) signal, DAT and G protein-coupled receptor 55 (GPR55)- associated fluorescent signals, GPR55/DAT immunofluorescence, and synaptosomal dopamine responses were assessed using 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane ( 18 F-FP-CIT) PET imaging, ex vivo fluorescent ligand imaging, confocal microscopy, and dopamine quantification. Marmosets acquired oral cocaine self-administration with preferential active lever responding. Repeated cocaine self-administration reduced striatal DAT-related 18 F-FP-CIT PET signal in vivo. In striatal slices, cocaine decreased fluorescent false neurotransmitter (FFN102)-associated DAT signal and increased T1117-associated GPR55 signal. Systemic 2-AG pretreatment reduced cocaine self-administration while restoring diminished circulating 2-AG levels. GPR55 and DAT immunofluorescent signals were colocalized in marmoset brain sections, and 2-AG enhanced cocaine-induced dopamine elevation in synaptosomal preparations. Taken together, these findings suggest that 2-AG attenuates cocaine-taking behavior and may be associated with GPR55/DAT-related dopaminergic responses in common marmosets.

Hallucinogens have been prescribed for the treatment of mental illnesses; however, reports on the dependence potential of hallucinogens across species remain inconsistent. Non-human primate (NHP) self-administration model are suitable for evaluating species-specific reinforcement behavior induced by hallucinogens. In this study, we demonstrated that 4-bromo-2,5-dimethoxyphenethylamine (2C-B) was self-administered orally in freely moving marmoset (Callithrix jacchus). 2C-B-treated mice did not demonstrate reinforcement behavior in self-administration paradigm as well as brain stimulation behavior in intracranial self-stimulation (ICSS) test. Interestingly, 2C-B-induced dopamine neuronal activity was demonstrated only in the brain of marmosets as evidenced by fluorescent false neurotransmitter assessment and measurement of synaptosome dopamine levels. We sought to study possible molecular mechanisms underlying this and docking simulations revealed that 2C-B occupied a binding pocket overlapping the canonical dopamine-binding site in both species but adopted a distinct interaction pattern in marmoset DAT involving Leu321. Pull-down assays demonstrated stronger DAT-associated 2C-B binding in marmosets than in mice. Furthermore, 2C-B produced greater inhibition of DAT-mediated FFN102 uptake in cells expressing marmoset or human DAT than in cells expressing mouse DAT, whereas substitution of Leu321 abolished this effect. Collectively, these findings demonstrate that 2C-B induces reward-related behaviors in marmosets and identify species-specific DAT-2C-B interactions as a potential mechanism underlying differential dopaminergic and behavioral responses across species.

Pretreatment expectancy is a plausible driver of contextual effects in pain care, yet evidence in acupuncture trials remains fragmented. We conducted a systematic review and meta-analysis of randomized trials of acupuncture or related needle- based interventions in adults with pain that reported within-arm associations between pretreatment expectancy and pain outcomes. Estimates were converted to correlation coefficients (r), with the positive values indicating better outcomes with higher expectancy, transformed to Fisher’s z, and pooled using random-effects models. Of the 28 trials eligible, 21 contributed to the primary meta-analysis. Higher expectancy was associated with better pain outcomes (pooled r = 0.214; 95% confidence interval [CI], 0.161–0.267; 95% prediction interval [PI], 0.043–0.373). Associations appeared larger during the treatment phase (up to the end-of-treatment, including immediate, mid-treatment, and end-of-treatment assessments; k = 17; r = 0.257; 95% CI, 0.197–0.315) than at follow-up (k = 4; r = 0.105; 95% CI, 0.045–0.164; subgroup p < 0.001), whereas within-context expectancy–pain associations were similar in verum and sham contexts. Pretreatment expectancy showed a consistent, modest association with pain outcomes in acupuncture trials, particularly near the treatment period. Standardized measurement and transparent analytical handling may improve trial interpretability.

Cat- and dog-derived allergenic proteins are important indoor exposure sources, but allergen exposure, IgE sensitization, and clinically manifest allergy are distinct biological and clinical states. Major molecules include the cat secretoglobin Fel d 1 and several dog lipocalins, including Can f 1, together with serum albumins, kallikreins, and other components that can contribute to species-specific sensitization or cross-reactivity. These proteins are transported in the environment on heterogeneous carriers such as dander fragments, dust, and aerosol particles, allowing both direct and indirect exposure. Clinical relevance depends on the concordance among exposure, molecular sensitization, symptoms, and host factors rather than on environmental detection alone. This narrative review integrates molecular allergen biology with environmental dissemination, IgE-mediated immune mechanisms, clinical phenotypes, diagnostic interpretation, and management. Particular emphasis is placed on the distinction between molecular homology, IgE cross-reactivity, and clinically relevant cross-allergy; on the complementary role and limitations of component-resolved diagnosis; and on the variable evidence supporting environmental control and cat- versus dog-allergen immunotherapy. Standard pharmacotherapy remains central to symptom control, whereas biologics and allergen-neutralizing approaches are restricted to specific indications or remain investigational. A precision-management framework therefore requires molecular results to be interpreted in the context of exposure–response concordance, clinical phenotype, and inflammatory disease characteristics.

Influenza A virus (IAV) remains a major global health threat despite available vaccines and antiviral agents, while current therapies are limited by drug resistance and safety concerns. Curcuminoids exhibit antiviral and anti-inflammatory activities but are constrained by poor water solubility and low bioavailability. To address these limitations, we investigated the antiviral and immunomodulatory properties of a water-solubilized curcuminoid nanoparticle formulation (C-S/M) in both in vitro and in vivo models of IAV infection. To evaluate the potential antiviral and anti-inflammatory effects of C-S/M, we performed a cytopathic effect (CPE) reduction assay in triplicate at 0.001 MOI and quantitative real-time PCR (qRT-PCR) targeting viral NS1 transcripts in MDCK cells. C-S/M suppressed viral NS1 vRNA levels in MDCK cells at lower curcuminoid-equivalent concentrations than native curcuminoids and attenuated IAV-induced TNF-α, IL-6, and IL-8 production. Furthermore, in vivo antiviral efficacy was evaluated in female C57BL/6 mice intranasally infected with IAV and treated orally with C-S/M. Survival, lung viral loads, pulmonary cytokine levels, and splenic immune cell phenotypes were analyzed. In IAV-infected mice, oral administration of C-S/M modestly improved survival and significantly reduced lung viral burden and pulmonary proinflammatory cytokine levels. In addition, in vivo C-S/M treatment was associated with recovery of virus-suppressed T-cell immune responses, including increased Th1 and activated CD8+ T cells, reduced regulatory T-cell expansion, and restoration of multifunctional CD4+ and CD8+ T cells. These findings suggest that C-S/M exerts antiviral and immunomodulatory effects in experimental IAV infection and may serve as a potential adjunctive candidate for further investigation against influenza-associated inflammation.