Immunopharmacology sessions at the 19th World Congress of Basic and Clinical Pharmacology 2023

No abstract available

Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma

The anti-malarial drug artesunate possesses anti-inflammatory and anti-oxidative actions in experimental asthma, comparable to corticosteroid. We hypothesized that artesunate may modulate disease-relevant metabolic alterations in allergic asthma. To explore metabolic profile changes induced by artesunate in allergic airway inflammation, we analysed bronchoalveolar lavage fluid (BALF) and serum from naïve and ovalbumin-induced asthma mice treated with artesunate, using both gas and liquid chromatography-mass spectrometry metabolomics. Pharmacokinetics analyses of serum and lung tissues revealed that artesunate is rapidly converted into the active metabolite dihydroartemisinin. Artesunate effectively suppressed BALF total and differential counts, and repressed BALF Th2 cytokines, IL-17, IL-12(p40), MCP-1 and G-CSF levels. Artesunate had no effects on both BALF and serum metabolome in naïve mice. Artesunate promoted restoration of BALF sterols (cholesterol, cholic acid and cortol), phosphatidylcholines and carbohydrates (arabinose, mannose and galactose) and of serum 18-oxocortisol, galactose, glucose and glucouronic acid in asthma. Artesunate prevented OVA-induced increases in pro-inflammatory metabolites from arginine–proline metabolic pathway, particularly BALF levels of urea and alanine and serum levels of urea, proline, valine and homoserine. Multiple statistical correlation analyses revealed association between altered BALF and serum metabolites and inflammatory cytokines. Dexamethasone failed to reduce urea level and caused widespread changes in metabolites irrelevant to asthma development. Here we report the first metabolome profile of artesunate treatment in experimental asthma. Artesunate restored specific metabolic perturbations in airway inflammation, which correlated well with its anti-inflammatory actions. Our metabolomics findings further strengthen the therapeutic value of using artesunate to treat allergic asthma

Integrated Circuit Packaging Recognition with Tilt Auto Adjustment using Deep Learning Approach

A deep-learning-based approach for recognizing integrated circuit (IC) packaging type is presented in this paper. The objective of this work is to design a deep-learning method that can recognize multiple types of packaging per detection, performing counting operations, and calculating the centre location of an IC with its tilting angle. The transfer learning from model You-Only-Look-Once (YOLO) v5 was chosen because it has been trained with the coco dataset and has a more reliable feature extraction system than the other models. In order to extract data from images, OpenCV was used, which allows the deep learning model to perform more efficient analysis of the input data. Apart from that, the principal component analysis (PCA) was used to estimate the angle of the IC in order to determine the rotation of each IC for the purpose of tilting adjustment. The developed model has an average confidence score of 85% and is capable of operating in a variety of conditions, as demonstrated by ANOVA analysis

Granulocyte-targeted therapies for airway diseases

The average respiration rate for an adult is 12-20 breaths per minute, which constantly exposes the lungs to allergens and harmful particles. As a result, respiratory diseases, which includes asthma, chronic obstructive pulmonary disease (COPD) and acute lower respiratory tract infections (LTRI), are a major cause of death worldwide. Although asthma, COPD and LTRI are distinctly different diseases with separate mechanisms of disease progression, they do share a common feature – airway inflammation with intense recruitment and activation of granulocytes and mast cells. Neutrophils, eosinophils, basophils, and mast cells are crucial players in host defense against pathogens and maintenance of lung homeostasis. Upon contact with harmful particles, part of the pulmonary defense mechanism is to recruit these cells into the airways. Despite their protective nature, overactivation or accumulation of granulocytes and mast cells in the lungs results in unwanted chronic airway inflammation and damage. As such, understanding the bright and the dark side of these leukocytes in lung physiology paves the way for the development of therapies targeting this important mechanism of disease. Here we discuss the role of granulocytes in respiratory diseases and summarize therapeutic strategies focused on granulocyte recruitment and activation in the lungs

VITAMIN E ISOFORM ¿-TOCOTRIENOL ALLEVIATES ASTHMA AND COPD

Ph.DDOCTOR OF PHILOSOPH

Ribosomal Protein S3 Gene Silencing Protects Against Cigarette Smoke-Induced Acute Lung Injury

Chronic obstructive pulmonary disease (COPD) is estimated to be the third leading cause of death by 2030. Transcription factor NF-κB may play a critical role in COPD pathogenesis. Ribosomal protein S3 (RPS3), a 40S ribosomal protein essential for executing protein translation, has recently been found to interact with the NF-κB p65 subunit and promote p65 DNA-binding activity. We sought to study whether RPS3 gene silencing could protect against cigarette-smoke (CS)-induced acute lung injury in a mouse model. Effects of an intratracheal RPS3 siRNA in CS-induced lung injury were determined by measuring bronchoalveolar lavage (BAL) fluid cell counts, levels of inflammatory and oxidative damage markers, and NF-κB translocation. Lung RPS3 level was found to be upregulated for the first time with CS exposure, and RPS3 siRNA blocked CS-induced neutrophil counts in BAL fluid. RPS3 siRNA suppressed CS-induced lung inflammatory mediator and oxidative damage marker levels, as well as nuclear p65 accumulation and transcriptional activation. RPS3 siRNA was able to disrupt CS extract (CSE)-induced NF-κB activation in an NF-κB reporter gene assay. We report for the first time that RPS3 gene silencing ameliorated CS-induced acute lung injury, probably via interruption of the NF-κB activity, postulating that RPS3 is a novel therapeutic target for COPD. Keywords: ribosomal protein S3, chronic obstructive pulmonary disease, NF-KB, siRNA, cigarette smok

Gene silencing of receptor-interacting protein 2 protects against cigarette smoke-induced acute lung injury

10.1016/j.phrs.2018.10.016PHARMACOLOGICAL RESEARCH139560-56

Vitamin E isoform gamma-tocotrienol protects against emphysema in cigarette smoke-induced COPD

10.1016/j.freeradbiomed.2017.06.023FREE RADICAL BIOLOGY AND MEDICINE110332-34

Andrographolide simultaneously augments Nrf2 antioxidant defense and facilitates autophagic flux blockade in cigarette smoke-exposed human bronchial epithelial cells

10.1016/j.taap.2018.10.005TOXICOLOGY AND APPLIED PHARMACOLOGY360120-13

Metabolomics reveals altered metabolic pathways in experimental asthma

10.1165/rcmb.2012-0246OCAmerican Journal of Respiratory Cell and Molecular Biology482204-211AJRB