The novel transmembrane G protein-coupled receptor, trace amine-associated receptor 1 (TAAR1), represents a potential, direct target for drugs of abuse and monoaminergic compounds, including amphetamines. For the first time, our studies have illustrated that there is an induction of TAAR1 mRNA expression in resting T lymphocytes in response to methamphetamine. Methamphetamine treatment for 6 h significantly increased TAAR1 mRNA expression (P < 0.001) and protein expression (P < 0.01) at 24 h. With the use of TAAR1 gene silencing, we demonstrate that methamphetamine-induced cAMP, a classic response to methamphetamine stimulation, is regulated via TAAR1. We also show by TAAR1 knockdown that the down-regulation of IL-2 in T cells by methamphetamine, which we reported earlier, is indeed regulated by TAAR1. Our results also show the presence of TAAR1 in human lymph nodes from HIV-1-infected patients, with or without a history of methamphetamine abuse. TAAR1 expression on lymphocytes was largely in the paracortical lymphoid area of the lymph nodes with enhanced expression in lymph nodes of HIV-1-infected methamphetamine abusers rather than infected-only subjects. In vitro analysis of HIV-1 infection of human PBMCs revealed increased TAAR1 expression in the presence of methamphetamine. In summary, the ability of methamphetamine to activate trace TAAR1 in vitro and to regulate important T cell functions, such as cAMP activation and IL-2 production; the expression of TAAR1 in T lymphocytes in peripheral lymphoid organs, such as lymph nodes; and our in vitro HIV-1 infection model in PBMCs suggests that TAAR1 may play an important role in methamphetamine -mediated immune-modulatory responses.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673484 | PMC |
http://dx.doi.org/10.1189/jlb.4A0814-395RR | DOI Listing |
Front Vet Sci
December 2024
School of Veterinary Medicine and Biomedical Sciences, Department of Small Animal Clinical Sciences, Texas A&M University, College Station, TX, United States.
Introduction: The objective of this study is to estimate reference values for medial retropharyngeal lymph nodes (MRLNs) measured in high-field (3T) MRI studies of the canine head/brain using transverse T2 spin-echo images and to determine if dogs with structural brain disease exhibit medial retropharyngeal lymph nodes that are larger than expected from estimated reference values.
Methods: The study population comprises 142 MRLNs from 71 dogs with no evidence of structural brain disease and normal CSF evaluation and 116 MRLNs from 58 dogs with structural brain disease confirmed by histopathology as of infectious or neoplastic origin, or to represent meningoencephalitis of unknown etiology.
Results: Based on this sample, MRLNs are expected to measure 2.
Front Surg
December 2024
Department of Thoracic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Objective: Lung cancer is the leading cause of cancer-related mortality. Lymph node involvement remains a crucial prognostic factor in non-small cell lung cancer (NSCLC), and the TNM system is the current standard for staging. However, it mainly considers the anatomical location of lymph nodes, neglecting the significance of node count.
View Article and Find Full Text PDFInfect Drug Resist
December 2024
Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Purpose: Periprosthetic joint infection (PJI) is a severe complication following joint replacement surgery, and there is a current lack of rapid, accurate, and non-invasive diagnostic methods. This study aims to assess the effectiveness of using dual-energy computed tomography (DECT) to quantify the maximum long and short axes of the external iliac lymph nodes (LNs) as a diagnostic tool for PJI.
Patients And Methods: In this prospective controlled study, 112 patients undergoing total hip or total knee revision surgery were enrolled.
Adv Sci (Weinh)
December 2024
Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
Paclitaxel (PTX) is a first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC) but it can induce indoleamine 2,3-dioxygenase (IDO) activation, which severely lowers down its immuno-chemotherapeutic effect. To address this issue, a smart peptide hydrogelator Nap-Phe-Phe-Phe-Lys-Ser-Thr-Gly-Gly-Lys-Ala-Pro-Arg-OH (Nap-T), which co-assembles with PTX and an IDO inhibitor GDC0919 to form a hydrogel GP@Gel Nap-T, is rationally designed. Upon specific phosphorylation by pyruvate kinase M2 (PKM2), an overexpressed biomarker of NSCLC, Nap-T is gradually converted to Nap-Phe-Phe-Phe-Lys-Ser-Thr(HPO)-Gly-Gly-Lys-Ala-Pro-Arg-OH (Nap-Tp), leading to dehydrogelation and sustained release of PTX and GDC0919 within NSCLC tissues.
View Article and Find Full Text PDFJ Control Release
December 2024
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Centre for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China. Electronic address:
Self-adjuvanted vaccine delivery platforms possess potential for targeted delivery of antigens and initiation of potent immune responses. Although aluminum-containing adjuvants have been approved and widely used in human vaccines, their effectiveness in inducing Th1-type immune responses is far from satisfactory. To facilitate antigen delivery and activate potent antitumor immune responses, a self-adjuvanted nanovaccine (CPBG-Al@OVA) is constructed by functionalizing aluminum hydroxide with β-1,3-glucan, which recognizes pattern recognition receptors via Dectin-1.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!