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Chronic respiratory diseases such as Chronic Obstructive Pulmonary Disease (COPD) and asthma have posed a significant healthcare and economic cost over a prolonged duration worldwide. At present, available treatments are limited to a range of preventive medicines, such as mono- or multiple-drug therapy, which necessitates daily use and are not considered as viable treatments to reverse the inflammatory processes of airway remodelling which is inclusive of the alteration of intra and extracellular matrix of the airway tract, death of epithelial cells, the increase in smooth muscle cell and the activation of fibroblasts. Hence, with the problem in mind a considerable body of study has been dedicated to comprehending the underlying factors that contribute to inflammation within the framework of these disorders. Hence, adequate literature that has unveiled the necessary cellular probing to reduce inflammation in the respiratory tract by improving the selectivity and precision of a novel treatment. However, through cellular probing cellular mechanisms such as the downregulation of various markers, interleukin 8, (IL-8), Interleukin 6 (IL-6), interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α) have been uncovered. Hence, to target such cellular probes implementation of phytoceuticals encapsulated in an advanced drug delivery system has shown potential to be a solution with in vitro and in vivo studies highlighting their anti-inflammatory and antioxidant effects. However, the high costs associated with advanced drug delivery systems and the limited literature focused exclusively on nanoparticles pose significant challenges. Additionally, the biochemical characteristics of phytoceuticals due to poor solubility, limited bioavailability, and difficulties in mass production makes it difficult to implement this product as a treatment for COPD and asthma. This study aims to examine the integration of many critical features in the context of their application for the treatment of chronic inflammation in respiratory disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is strongly linked to cigarette smoke, which contains toxins that induce oxidative stress and airway inflammation, ultimately leading to premature airway epithelial cell senescence and exacerbating COPD progression. Current treatments for COPD are symptomatic and hampered by limited efficacy and severe side effects. This highlights the need to search for an optimal therapeutic candidate to address the root causes of these conditions. This study investigates the possible potential of poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles encapsulating the plant-based bioactive compound 18-β-glycyrrhetinic acid (18βGA) as a strategy to intervene in cigarette smoke extract (CSE)-induced oxidative stress, inflammation, and senescence, in vitro. We prepared 18βGA-PLGA nanoparticles, and assessed their effects on cell viability, reactive oxygen species (ROS) production, anti-senescence properties (expression of senescence-associated β galactosidase and p21 mRNA), and expression of pro-inflammatory genes (CXCL-1, IL-6, TNF-α) and inflammation-related proteins (IL-8, IL-15, RANTES, MIF). The highest non-toxic concentration of 18βGA-PLGA nanoparticles to healthy human broncho epithelial cell line BCiNS1.1 was identified as 5 µM. These nanoparticles effectively mitigated cigarette smoke-induced inflammation, reduced ROS production, protected against cellular aging, and counteracted the effects of CSE on the expression of the inflammation-related genes and proteins. This study underscores the potential of 18βGA encapsulated in PLGA nanoparticles as a promising therapeutic approach to alleviate cigarette smoke-induced oxidative stress, inflammation, and senescence. Further research is needed to explore the translational potential of these findings in clinical and in vivo settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Pulmonary infections have a profound influence on global mortality rates. Medicinal plants offer a promising approach to address this challenge, providing nontoxic alternatives with higher levels of public acceptance and compliance, particularly in regions where access to conventional medications or diagnostic resources may be limited. Understanding the pathophysiology of viruses and bacteria enables researchers to identify biomarkers essential for triggering diseases. This knowledge allows the discovery of biological molecules capable of either preventing or alleviating symptoms associated with these infections. In this review, medicinal plants that have an effect on COVID-19, influenza A, bacterial and viral pneumonia, and tuberculosis are discussed. Drug delivery has been briefly discussed as well. It examines the effect of bioactive constituents of these plants and synthesizes findings from in vitro, in vivo, and clinical studies conducted over the past decade. In conclusion, many medicinal plants can be used to treat pulmonary infections, but further in-depth studies are needed as most of the current studies are only at preliminary stages. Extensive investigation and clinical studies are warranted to fully elucidate their mechanisms of action and optimize their use in clinical practice., (© 2024 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.)

Dyslipidaemia describes the condition of abnormal lipid levels in a person's bloodstream. Since the 1980s, statin medications have been used to treat dyslipidaemia and other comorbidities, such as stroke risk and atherosclerosis. Statin medications were initially synthesised from fungal metabolites, but many synthetic statin drugs have been manufactured since then. Statin medication is quite effective in reducing total cholesterol levels in the bloodstream, but it has limitations. Due to their poor water solubility, statin drugs possess poor oral bioavailability, which hinders their therapeutic efficacy. Nanoparticle drug delivery technology has been shown to improve the pharmacokinetic profiles of many drug classes, and statins have great potential to benefit from this. This paper reviewed the currently available literature on nanoparticle statin medication and evaluated the possible improvements that can be made to the pharmacokinetic profile and efficacy of conventional statin medication. It was found that the oral bioavailability of nanoparticle medication consistently outperformed conventional medication by up to 400% in some cases. Substantial improvements in time to peak plasma concentration and plasma concentration peaks were also found, and increased periods in circulation before excretion were shown. It was concluded that nanoparticle technology has the potential to completely replace conventional statin medication as it offers more significant benefits with minimal drawbacks. Upon further study and development, the manufacture of nanoparticle statin medication should become feasible enough for large-scale application, which will significantly benefit patients and unburden healthcare systems., (© 2024. The Author(s).)

Lung cancer is one of the most diagnosed types of cancer worldwide, accounting to one fifth of cancer-related deaths. The high prevalence of lung cancer (LC) is due to various factors such as environmental pollution or lifestyle factors such as cigarette smoking. Non-small cell lung cancer (NSCLC) is the most diagnosed type of lung cancer. Despite the availability of several lines of treatment for NSCLC, including surgery, chemotherapy, radiotherapy, immunotherapy, and combinations of these, this disease still has very low survival rate, highlighting the urgent need to develop novel therapeutics. Phytoceuticals, or plant-derived bioactives are a promising source of biologically active compounds. Among these, curcumin is particularly relevant due to its wide range of anticancer, antioxidant, and anti-inflammatory activity. However, its poor solubility causes low bioavailability, severely limiting its clinical application. Encapsulation of curcumin in nanoparticle-based delivery systems such as liposomes holds promise to overcome this limitation. In the present study, we demonstrate promising in vitro anticancer affect or curcumin-loaded liposomes (PlexoZome®) on A549 human lung adenocarcinoma cells. The study reveals how liposomal curcumin functionally supresses the proliferation, migration, and colony formation of these cells whilst also drastically reducing the expression of multiple cancer marker proteins. This work provides foundational data for the development of a curcumin-based nano formulation to be used as therapy for NSCLC., Competing Interests: The authors have no conflict of interest to declare., (© 2024 Published by Elsevier Ltd.)

Inhalation of particulate matter (PM), one of the many components of air pollution, is associated with the development and exacerbation of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD). COPD is one of the leading causes of global mortality and morbidity, with a paucity of therapeutic options and a significant contributor to global health expenditure. This review aims to provide a mechanistic understanding of the cellular and molecular pathways that lead to the development of COPD following chronic PM exposure. Our review describes how the inhalation of PM can lead to lung parenchymal destruction and cellular senescence due to chronic pulmonary inflammation and oxidative stress. Following inhalation of PM, significant increases in a range of pro-inflammatory cytokines, mediated by the nuclear factor kappa B pathway are reported. This review also highlights how the inhalation of PM can lead to deleterious chronic oxidative stress persisting in the lung post-exposure. Furthermore, our work summarises how PM inhalation can lead to airway remodelling, with increases in pro-fibrotic cytokines and collagen deposition, typical of COPD. This paper also accentuates the interconnection and possible synergism between the pathophysiological mechanisms leading to COPD. Our work emphasises the serious health consequences of PM exposure on respiratory health. Elucidation of the cellular and molecular mechanisms can provide insight into possible therapeutic options. Finally, this review should serve as a stark reminder of the need for genuine action on air pollution to decrease the associated health burden on our growing global population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Lung cancer is among leading causes of death worldwide. The five-year survival rate of this disease is extremely low (17.8 %), mainly due to difficult early diagnosis and to the limited efficacy of currently available chemotherapeutics. This underlines the necessity to develop innovative therapies for lung cancer. In this context, drug repurposing represents a viable approach, as it reduces the turnaround time of drug development removing costs associated to safety testing of new molecular entities. Ribavirin, an antiviral molecule used to treat hepatitis C virus infections, is particularly promising as repurposed drug for cancer treatment, having shown therapeutic activity against glioblastoma, acute myeloid leukemia, and nasopharyngeal carcinoma. In the present study, we thoroughly investigated the in vitro anticancer activity of ribavirin against A549 human lung adenocarcinoma cells. From a functional standpoint, ribavirin significantly inhibits cancer hallmarks such as cell proliferation, migration, and colony formation. Mechanistically, ribavirin downregulates the expression of numerous proteins and genes regulating cell migration, proliferation, apoptosis, and cancer angiogenesis. The anticancer potential of ribavirin was further investigated in silico through gene ontology pathway enrichment and protein-protein interaction networks, identifying five putative molecular interactors of ribavirin (Erb-B2 Receptor Tyrosine Kinase 4 (Erb-B4); KRAS; Intercellular Adhesion Molecule 1 (ICAM-1); amphiregulin (AREG); and neuregulin-1 (NRG1)). These interactions were characterized via molecular docking and molecular dynamic simulations. The results of this study highlight the potential of ribavirin as a repurposed chemotherapy against lung cancer, warranting further studies to ascertain the in vivo anticancer activity of this molecule., Competing Interests: Declaration of competing interest The authors of the manuscript “Computational and Biological Approaches in Repurposing Ribavirin for Lung Cancer Treatment: Unveiling Antitumorigenic Strategies”, submitted to the journal “Life Sciences”, have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Curcumin, the principal curcuminoid of turmeric (Curcuma longa extract), is very well known for its multiple biological therapeutic activities, particularly its anti-inflammatory and antioxidant potential. However, due to its low water solubility, it exhibits poor bioavailability. In order to overcome this problem, in the current study, we have employed liposomal technology to encapsulate curcumin with the aim of enhancing its therapeutic efficacy. The curcumin-loaded liposomes (PlexoZome®) were tested on a cigarette smoke extract-induced Chronic Obstructive Pulmonary Disease (COPD) in vitro model using minimally immortalized human bronchial epithelial cells (BCiNS1.1). The anti-senescence and anti-inflammatory properties of PlexoZome® were explored. 5 µM PlexoZome® curcumin demonstrated anti-senescent activity by decrease in X-gal positive cells, and reduction in the expression of p16 and p21 in immunofluorescence staining. Moreover, PlexoZome® curcumin also demonstrated a reduction in proteins related to senescence (osteopontin, FGF basic and uPAR) and inflammation (GM-CSF, EGF and ST2). Overall, the results clearly demonstrate the therapeutic potential of curcumin encapsulated liposomes in managing CSE induced COPD, providing a new direction to respiratory clinics., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Lung cancer (LC) is the leading cause of cancer-related mortality, and it is caused by many factors including cigarette smoking. Despite numerous treatment strategies for LC, its five-year survival is still poor (<20 %), attributable to treatment resistance and lack of early diagnosis and intervention. Importantly, LC incidence is higher in patients affected by chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disorder (COPD), and LC shares with other CRDs common pathophysiological features including chronic inflammation, oxidative stress, cellular senescence, and airway remodelling. Remodelling is a complex process resulting from the aberrant activation of tissue repair secondary to chronic inflammation, oxidative stress, and tissue damage observed in the airways of CRD patients, and it is characterized by irreversible airway structural and functional alterations, concomitantly with tissue fibrosis, epithelial-to-mesenchymal transition (EMT), excessive collagen deposition, and thickening of the basement membrane. Many processes involved in remodelling, particularly EMT, are also fundamental for LC pathogenesis, highlighting a potential connection between CRDs and LC. This provides rationale for the development of novel treatment strategies aimed at targeting components of the remodelling pathways. In this study, we tested the in vitro therapeutic activity of rat fecal microbiome extract (FME) on A549 human lung adenocarcinoma cells. We show that treatment with FME significantly downregulates the expression of six proteins whose function is at the forefront between airway remodelling and LC development: Snail, SPARC, MUC-1, Osteopontin, MMP-2, and HIF-1α. The results of this study, if confirmed by further investigations, provide proof-of-concept for a novel approach in the treatment of LC, focused on tackling the airway remodelling mechanisms underlying the increased susceptibility to develop LC observed in CRD patients., Competing Interests: Declaration of Competing Interest The authors of the manuscript submitted to the journal “Pathology - Research and Practice”, have no conflict of interest to declare., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Chronic respiratory diseases (CRDs) represent a significant proportion of global health burden, with a wide spectrum of varying, heterogenic conditions largely affecting the pulmonary system. Recent advances in immunology and respiratory biology have highlighted the systemic impact of these diseases, notably through the elucidation of the lung-eye axis. The current review focusses on understanding the pivotal role of the lung-eye axis in the pathogenesis and progression of chronic respiratory infections and diseases. Existing literature published on the immunological crosstalk between the eye and the lung has been reviewed. The various roles of the ocular microbiome in lung health are also explored, examining the eye as a gateway for respiratory virus transmission, and assessing the impact of environmental irritants on both ocular and respiratory systems. This novel concept emphasizes a bidirectional relationship between respiratory and ocular health, suggesting that respiratory diseases may influence ocular conditions and vice versa, whereby this conception provides a comprehensive framework for understanding the intricate axis connecting both respiratory and ocular health. These aspects underscore the need for an integrative approach in the management of chronic respiratory diseases. Future research should further elucidate the in-depth molecular mechanisms affecting this axis which would pave the path for novel diagnostics and effective therapeutic strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: This project has received funding from Pharmako Biotechnologies. The PlexoZome® Curcumin formulation we have tested is a product of Pharmako Biotechnologies, further information about it can be found on their official website: https://www.pharmako.com.au.

Chronic inflammation, oxidative stress, and airway remodelling represent the principal pathophysiological features of chronic respiratory disorders. Inflammation stimuli like lipopolysaccharide (LPS) activate macrophages and dendritic cells, with concomitant M1 polarization and release of pro-inflammatory cytokines. Chronic inflammation and oxidative stress lead to airway remodelling causing irreversible functional and structural alterations of the lungs. Airway remodelling is multifactorial, however, the hormone transforming growth factor-β (TGF-β) is one of the main contributors to fibrotic changes. The signalling pathways mediating inflammation and remodelling rely both on the transcription factor nuclear factor-κB (NFκB), underlying the potential of NFκB inhibition as a therapeutic strategy for chronic respiratory disorders. In this study, we encapsulated an NFκB-inhibiting decoy oligodeoxynucleotide (ODN) in spermine-functionalized acetalated dextran (SpAcDex) nanoparticles and tested the in vitro anti-inflammatory and anti-remodelling activity of this formulation. We show that NF-κB ODN nanoparticles counteract inflammation by reversing LPS-induced expression of the activation marker CD40 in myeloid cells and counteracts remodelling features by reversing the TGF-β-induced expression of collagen I and α-smooth muscle actin in human dermal fibroblast. In summary, our study highlights the great potential of inhibiting NFκB via decoy ODN as a therapeutic strategy tackling multiple pathophysiological features underlying chronic respiratory conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Lung cancer stands as the primary contributor to cancer-related fatalities worldwide, affecting both genders. Two primary types exist where non-small cell lung cancer (NSCLC), accounts for 80-85% and SCLC accounts for 10-15% of cases. NSCLC subtypes include adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Smoking, second-hand smoke, radon gas, asbestos, and other pollutants, genetic predisposition, and COPD are lung cancer risk factors. On the other hand, stresses such as DNA damage, telomere shortening, and oncogene activation cause a prolonged cell cycle halt, known as senescence. Despite its initial role as a tumor-suppressing mechanism that slows cell growth, excessive or improper control of this process can cause age-related diseases, including cancer. Cellular senescence has two purposes in lung cancer. Researchers report that senescence slows tumor growth by constraining multiplication of impaired cells. However, senescent cells also demonstrate the pro-inflammatory senescence-associated secretory phenotype (SASP), which is widely reported to promote cancer. This review will look at the role of cellular senescence in lung cancer, describe its diagnostic markers, ask about current treatments to control it, look at case studies and clinical trials that show how senescence-targeting therapies can be used in lung cancer, and talk about problems currently being faced, and possible solutions for the same in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The escalating prevalence of lung diseases underscores the need for innovative therapies. Dysbiosis in human body microbiome has emerged as a significant factor in these diseases, indicating a potential role for synbiotics in restoring microbial equilibrium. However, effective delivery of synbiotics to the target site remains challenging. Here, we aim to explore suitable nanoparticles for encapsulating synbiotics tailored for applications in lung diseases. Nanoencapsulation has emerged as a prominent strategy to address the delivery challenges of synbiotics in this context. Through a comprehensive review, we assess the potential of nanoparticles in facilitating synbiotic delivery and their structural adaptability for this purpose. Our review reveals that nanoparticles such as nanocellulose, starch, and chitosan exhibit high potential for synbiotic encapsulation. These offer flexibility in structure design and synthesis, making them promising candidates for addressing delivery challenges in lung diseases. Furthermore, our analysis highlights that synbiotics, when compared to probiotics alone, demonstrate superior anti-inflammatory, antioxidant, antibacterial and anticancer activities. This review underscores the promising role of nanoparticle-encapsulated synbiotics as a targeted and effective therapeutic approach for lung diseases, contributing valuable insights into the potential of nanomedicine in revolutionizing treatment strategies for respiratory conditions, ultimately paving the way for future advancements in this field., Competing Interests: Declaration of competing interest The authors of the submitted manuscript have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Tobacco smoking is a leading cause of preventable mortality, and it is the major contributor to diseases such as COPD and lung cancer. Cigarette smoke compromises the pulmonary antiviral immune response, increasing susceptibility to viral infections. There is currently no therapy that specifically addresses the problem of impaired antiviral response in cigarette smokers and COPD patients, highlighting the necessity to develop novel treatment strategies. 18-β-glycyrrhetinic acid (18-β-gly) is a phytoceutical derived from licorice with promising anti-inflammatory, antioxidant, and antiviral activities whose clinical application is hampered by poor solubility. This study explores the therapeutic potential of an advanced drug delivery system encapsulating 18-β-gly in poly lactic-co-glycolic acid (PLGA) nanoparticles in addressing the impaired antiviral immunity observed in smokers and COPD patients. Exposure of BCi-NS1.1 human bronchial epithelial cells to cigarette smoke extract (CSE) resulted in reduced expression of critical antiviral chemokines (IP-10, I-TAC, MIP-1α/1β), mimicking what happens in smokers and COPD patients. Treatment with 18-β-gly-PLGA nanoparticles partially restored the expression of these chemokines, demonstrating promising therapeutic impact. The nanoparticles increased IP-10, I-TAC, and MIP-1α/1β levels, exhibiting potential in attenuating the negative effects of cigarette smoke on the antiviral response. This study provides a novel approach to address the impaired antiviral immune response in vulnerable populations, offering a foundation for further investigations and potential therapeutic interventions. Further studies, including a comprehensive in vitro characterization and in vivo testing, are warranted to validate the therapeutic efficacy of 18-β-gly-PLGA nanoparticles in respiratory disorders associated with compromised antiviral immunity., Competing Interests: Declaration of Competing Interest The authors of the manuscript “18-β-glycyrrhetinic acid-loaded polymeric nanoparticles attenuate cigarette smoke-induced markers of impaired antiviral response in vitro”, submitted to the journal “Pathology - Research and Practice”, have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Lung cancer (LC) remains a leading cause of cancer-related mortality worldwide, necessitating the exploration of innovative therapeutic strategies. This study delves into the in vitro potential of liposomal therapeutics utilizing Curcumin-loaded PlexoZome® (CUR-PLXZ) in targeting EpCAM/TROP1 and Estrogen Receptor Alpha (ERα) signalling pathways for LC management. The prevalence of LC, particularly non-small cell lung cancer (NSCLC), underscores the urgent need for effective treatments. Biomarkers like EpCAM/TROP1 and ERα/NR3A1 play crucial roles in guiding targeted therapies and influencing prognosis. EpCAM plays a key role in cell-cell adhesion and signalling along with ERα which is a nuclear receptor that binds estrogen and regulates gene expression in response to hormonal signals. In LC, both often get overexpressed and are associated with tumour progression, metastasis, and poor prognosis. Curcumin, a phytochemical with diverse therapeutic properties, holds promise in targeting these pathways. However, its limited solubility and bioavailability necessitate advanced formulations like CUR-PLXZ. Our study investigates the biological significance of these biomarkers in the A549 cell line and explores the therapeutic potential of CUR-PLXZ, which modulates the expression of these two markers. An in vitro analysis of the A549 human lung adenocarcinoma cell line identified that CUR-PLXZ at a dose of 5 μM effectively inhibited the expression of EpCAM and ERα. This finding paves the way for targeted intervention strategies in LC management., Competing Interests: Declaration of Competing Interest This project has received funding from Pharmako Biotechnologies. The PlexoZome® Curcumin formulation we have tested is a product of Pharmako Biotechnologies, further information about it can be found on their official website. https://www.pharmako.com.au., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The intricate relationship between smoking and the effects of the antiplatelet drug clopidogrel has been termed the "smoker's paradox". This paradox details the enhanced efficacy of clopidogrel in smokers compared to non-smokers. This review begins with an exploration of the proposed mechanisms of the smoker's paradox, particularly drawing attention to the induction of cytochrome P450 (CYP) isoenzymes via tobacco smoke, specifically the enzymes CYP1A2 and CYP2C19. Moreover, an investigation of the effects of genetic variability on the smoker's paradox was undertaken from both clinical and molecular perspectives, delving into the effects of ethnicity and genetic polymorphisms. The intriguing role of CYP1A2 genotypes and the response to clopidogrel in smoking and non-smoking populations was examined conferring insight into the individuality rather than universality of the smoker's paradox. CYP1A2 induction is hypothesised to elucidate the potency of smoking in exerting a counteracting effect in those taking clopidogrel who possess CYP2C19 loss of function polymorphisms. Furthermore, we assess the comparative efficacies of clopidogrel and other antiplatelet agents, namely prasugrel and ticagrelor. Studies indicated that prasugrel and ticagrelor provided a more consistent effect and further reduced platelet reactivity compared to clopidogrel within both smoking and non-smoking populations. Personalised dosing was another focus of the review considering patient comorbidities, genetic makeup, and smoking status with the objective of improving the antiplatelet response of those taking clopidogrel. In summation, this review provides insight into multiple areas of research concerning clopidogrel and the smoker's paradox taking into account proposed mechanisms, genetics, other antiplatelet agents, and personalised dosing., Competing Interests: Declaration of Competing Interest The authors of the manuscript “Investigation of smoking on the antiplatelet response to clopidogrel: Unravelling the Smoker’s Paradox.”, submitted to the journal “Pathology – Research and Practice”, have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Epilepsy is a neurological disorder characterized by overstimulation of neurotransmitters and uncontrolled seizures. Current medications for epilepsy result in adverse effects or insufficient seizure control, highlighting the necessity to develop alternative therapies. Cannabidiol (CBD), derived from cannabis plants, has been popularly explored as an alternative. CBD is shown to have anti-convulsivatng and muscle-relaxing properties, which have been used in patients with epilepsy with promising results. Current research explores varying dosages in either adult or paediatric patients, with little or no comparison between the two populations. In this review, we aim at consolidating this data and comparing the effect and pharmacokinetic properties of CBD across these two patient populations. When comparing the absorption, there was insufficient data to show differences between paediatric and adult patients. Similarly, limited information was available in comparing the distribution of CBD, but a higher volume of distribution was found in the paediatric population. From the metabolism perspective, the paediatric population had a greater success rate when treated with the drug compared to the adult population. In the elimination, there were no clear distinctions in the clearance rate between the two populations. The drug's half-life was highly variable in both populations, with paediatrics having a lower range than adults. In summary, the paediatric population had a more significant reduction in the severity of seizures compared to the adult population upon CBD treatment. The complexity in which CBD operates highlights the need for further studies of the compound to further understand why differences occur between these two populations., Competing Interests: Declaration of competing interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are among the leading causes of mortality worldwide. Cigarette smoking is among the main aetiologic factors for both ailments. These diseases share common pathogenetic mechanisms including inflammation, oxidative stress, and tissue remodelling. Current therapeutic approaches are limited by low efficacy and adverse effects. Consequentially, LC has a 5-year survival of < 20%, while COPD is incurable, underlining the necessity for innovative treatment strategies. Two promising emerging classes of therapy against these diseases include plant-derived molecules (phytoceuticals) and nucleic acid-based therapies. The clinical application of both is limited by issues including poor solubility, poor permeability, and, in the case of nucleic acids, susceptibility to enzymatic degradation, large size, and electrostatic charge density. Nanoparticle-based advanced drug delivery systems are currently being explored as flexible systems allowing to overcome these limitations. In this review, an updated summary of the most recent studies using nanoparticle-based advanced drug delivery systems to improve the delivery of nucleic acids and phytoceuticals for the treatment of LC and COPD is provided. This review highlights the enormous relevance of these delivery systems as tools that are set to facilitate the clinical application of novel categories of therapeutics with poor pharmacokinetic properties., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The purpose of this study was to evaluate the potential of zerumbone-loaded liquid crystalline nanoparticles (ZER-LCNs) in the protection of broncho-epithelial cells and alveolar macrophages against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro. The effect of the treatment of ZER-LCNs on in vitro cell models of cigarette smoke extract (CSE)-treated mouse RAW264.7 and human BCi-NS1.1 basal epithelial cell lines was evaluated for their anti-inflammatory, antioxidant and anti-senescence activities using colorimetric and fluorescence-based assays, fluorescence imaging, RT-qPCR and proteome profiler kit. The ZER-LCNs successfully reduced the expression of pro-inflammatory markers including Il-6, Il-1β and Tnf-α, as well as the production of nitric oxide in RAW 264.7 cells. Additionally, ZER-LCNs successfully inhibited oxidative stress through reduction of reactive oxygen species (ROS) levels and regulation of genes, namely GPX2 and GCLC in BCi-NS1.1 cells. Anti-senescence activity of ZER-LCNs was also observed in BCi-NS1.1 cells, with significant reductions in the expression of SIRT1, CDKN1A and CDKN2A. This study demonstrates strong in vitro anti-inflammatory, antioxidative and anti-senescence activities of ZER-LCNs paving the path for this formulation to be translated into a promising therapeutic agent for chronic respiratory inflammatory conditions including COPD and asthma., (© 2023. The Author(s).)