Faecal microbial transfer and complex carbohydrates mediate protection against COPD.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DESIGN: Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. RESULTS: FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. CONCLUSION: The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.

Exploring the role of antibiotics and steroids in managing respiratory diseases.

Respiratory diseases (RDs), such as chronic obstructive pulmonary disease, cystic fibrosis, asthma, and pneumonia, are associated with significant morbidity and mortality. Treatment usually consists of antibiotics and steroids. Relevant published literature reviews, studies, and clinical trials were accessed from institutional and electronic databases. The keywords used were respiratory diseases, steroids, antibiotics, and combination of steroids and antibiotics. Selected articles and literature were carefully reviewed. Antibiotics are often prescribed as the standard therapy to manage RDs. Types of causative respiratory pathogens, spectrum of antibiotics activity, route of administration, and course of therapy determine the type of antibiotics that are prescribed. Despite being associated with good clinical outcome, treatment failure and recurrence rate are still high. In addition, antibiotic resistance has been widely reported due to bacterial mutations in response to the use of antibiotics, which render them ineffective. Nevertheless, there has been a growing demand for corticosteroids (CS) and antibiotics to treat a wide variety of diseases, including various airway diseases, due to their immunosuppressive and anti-inflammatory properties. The use of CS is well established and there are different formulations based on the diseases, such as topical administration, tablets, intravenous injections, and inhaled preparations. Both antibiotics and CS possess similar properties in terms of their anti-inflammatory effects, especially regulating cytokine release. Thus, the current review examines and discusses the different applications of antibiotics, CS, and their combination in managing various RDs. Drawbacks of these interventions are also discussed.

Targeting intercellular adhesion molecule-1 (ICAM-1) to reduce rhinovirus-induced acute exacerbations in chronic respiratory diseases.

The chronic respiratory non-communicable diseases, asthma and chronic obstructive pulmonary disease (COPD) are among the leading causes of global mortality and morbidity. Individuals suffering from these diseases are particularly susceptible to respiratory infections caused by bacterial and/or viral pathogens, which frequently result in exacerbation of symptoms, lung function decline, frequent hospital emergency visits and increased socioeconomic burden. Human rhinoviruses (HRV) remain the major viral pathogen group implicated in exacerbations of both asthma and COPD. The rhinoviral entry into the host lung epithelium is facilitated primarily by the adhesion site ("receptor") intercellular adhesion molecule-1 (ICAM-1), coincidentally expressed on the respiratory epithelium in these conditions. Multiple observations of increased airway ICAM-1 protein in asthmatics, smokers and smoking-related COPD have been recorded in the literature. However, the lack of robust therapies for COPD in particular has triggered a renewed interest in assessing receptor antagonism-based anti-viral strategies for treatment of intercurrent viral infections in those with pre-existing chronic lung diseases. Given the crucial role ICAM-1 plays in facilitating HRV adhesion and, thus, transmissibility to the host respiratory system, as well as the up-regulation of ICAM-1 by smoking, we summarize the role of HRV in smoking-induced COPD and especially highlight the role of ICAM-1 in epithelial viral adhesion and chronic lung disease progression. Further, the review also sheds light specifically on evolving precision therapeutic strategies in blocking ICAM-1 for preventing viral adhesion and exacerbations of COPD.

Concepts of advanced therapeutic delivery systems for the management of remodeling and inflammation in airway diseases.

Chronic respiratory disorders affect millions of people worldwide. Pathophysiological changes to the normal airway wall structure, including changes in the composition and organization of its cellular and molecular constituents, are referred to as airway remodeling. The inadequacy of effective treatment strategies and scarcity of novel therapies available for the treatment and management of chronic respiratory diseases have given rise to a serious impediment in the clinical management of such diseases. The progress made in advanced drug delivery, has offered additional advantages to fight against the emerging complications of airway remodeling. This review aims to address the gaps in current knowledge about airway remodeling, the relationships between remodeling, inflammation, clinical phenotypes and the significance of using novel drug delivery methods.

Treatment of chronic airway diseases using nutraceuticals: Mechanistic insight.

Respiratory diseases, both acute and chronic, are reported to be the leading cause of morbidity and mortality, affecting millions of people globally, leading to high socio-economic burden for the society in the recent decades. Chronic inflammation and decline in lung function are the common symptoms of respiratory diseases. The current treatment strategies revolve around using appropriate anti-inflammatory agents and bronchodilators. A range of anti-inflammatory agents and bronchodilators are currently available in the market; however, the usage of such medications is limited due to the potential for various adverse effects. To cope with this issue, researchers have been exploring various novel, alternative therapeutic strategies that are safe and effective to treat respiratory diseases. Several studies have been reported on the possible links between food and food-derived products in combating various chronic inflammatory diseases. Nutraceuticals are examples of such food-derived products which are gaining much interest in terms of its usage for the well-being and better human health. As a consequence, intensive research is currently aimed at identifying novel nutraceuticals, and there is an emerging notion that nutraceuticals can have a positive impact in various respiratory diseases. In this review, we discuss the efficacy of nutraceuticals in altering the various cellular and molecular mechanisms involved in mitigating the symptoms of respiratory diseases.

The Underappreciated Role of Epithelial Mesenchymal Transition in Chronic Obstructive Pulmonary Disease and Its Strong Link to Lung Cancer.

The World Health Organisation reported COPD to be the third leading cause of death globally in 2019, and in 2020, the most common cause of cancer death was lung cancer; when these linked conditions are added together they come near the top of the leading causes of mortality. The cell-biological program termed epithelial-to-mesenchymal transition (EMT) plays an important role in organ development, fibrosis and cancer progression. Over the past decade there has emerged a substantial literature that also links EMT specifically to the pathophysiology of chronic obstructive pulmonary disease (COPD) as primarily an airway fibrosis disease; COPD is a recognised strong independent risk factor for the development of lung cancer, over and above the risks associated with smoking. In this review, our primary focus is to highlight these linkages and alert both the COPD and lung cancer fields to these complex interactions. We emphasise the need for inter-disciplinary attention and research focused on the likely crucial roles of EMT (and potential for its inhibition) with recognition of its strategic place mechanistically in both COPD and lung cancer. As part of this we discuss the future potential directions for novel therapeutic opportunities, including evidence-based strategic repurposing of currently used familiar/approved medications.

An Appraisal of the Current Scenario in Vaccine Research for COVID-19.

The recent coronavirus disease 2019 (COVID-19) outbreak has drawn global attention, affecting millions, disrupting economies and healthcare modalities. With its high infection rate, COVID-19 has caused a colossal health crisis worldwide. While information on the comprehensive nature of this infectious agent, SARS-CoV-2, still remains obscure, ongoing genomic studies have been successful in identifying its genomic sequence and the presenting antigen. These may serve as promising, potential therapeutic targets in the effective management of COVID-19. In an attempt to establish herd immunity, massive efforts have been directed and driven toward developing vaccines against the SARS-CoV-2 pathogen. This review, in this direction, is aimed at providing the current scenario and future perspectives in the development of vaccines against SARS-CoV-2.

Interleukin-13: A pivotal target against influenza-induced exacerbation of chronic lung diseases.

Non-communicable, chronic respiratory diseases (CRDs) affect millions of individuals worldwide. The course of these CRDs (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) are often punctuated by microbial infections that may result in hospitalization and are associated with increased risk of morbidity and mortality, as well as reduced quality of life. Interleukin-13 (IL-13) is a key protein that regulates airway inflammation and mucus hypersecretion. There has been much interest in IL-13 from the last two decades. This cytokine is believed to play a decisive role in the exacerbation of inflammation during the course of viral infections, especially, in those with pre-existing CRDs. Here, we discuss the common viral infections in CRDs, as well as the potential role that IL-13 plays in the virus-induced disease pathogenesis of CRDs. We also discuss, in detail, the immune-modulation potential of IL-13 that could be translated to in-depth studies to develop IL-13-based therapeutic entities.

Targeting LIN28: a new hope in prostate cancer theranostics.

The mortality and morbidity rates for prostate cancer have recently increased to alarming levels, rising higher than lung cancer. Due to a lack of drug targets and molecular probes, existing theranostic techniques are limited. Human LIN28A and its paralog LIN28B overexpression are associated with a number of tumors resulting in a remarkable increase in cancer aggression and poor prognoses. The current review aims to highlight recent work identifying the key roles of LIN28A and LIN28B in prostate cancer, and to instigate further preclinical and clinical research in this important area.

Fully integrating pathophysiological insights in COPD: an updated working disease model to broaden therapeutic vision.

Our starting point is that relatively new findings into the pathogenesis and pathophysiology of airway disease in smokers that lead to chronic obstructive pulmonary disease (COPD) need to be reassessed as a whole and integrated into "mainstream" thinking along with traditional concepts which have stood the test of time. Such a refining of the accepted disease paradigm is urgently needed as thinking on therapeutic targets is currently under active reconsideration. We feel that generalised airway wall "inflammation" is unduly over-emphasised, and highlight the patchy and variable nature of the pathology (with the core being airway remodelling). In addition, we present evidence for airway wall disease in smokers/COPD as including a hypocellular, hypovascular, destructive, fibrotic pathology, with a likely spectrum of epithelial-mesenchymal transition states as significant drivers of this remodelling. Furthermore, we present data from a number of research modalities and integrate this with the aetiology of lung cancer, the role of chronic airway luminal colonisation/infection by a specific group of "respiratory" bacteria in smokers (which results in luminal inflammation) and the central role for oxidative stress on the epithelium. We suggest translation of these insights into more focus on asymptomatic smokers and early COPD, with the potential for fresh preventive and therapeutic approaches.

Rutin loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro.

Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.

An overview of vaccine development for COVID-19.

The COVID-19 pandemic continues to endanger world health and the economy. The causative SARS-CoV-2 coronavirus has a unique replication system. The end point of the COVID-19 pandemic is either herd immunity or widespread availability of an effective vaccine. Multiple candidate vaccines - peptide, virus-like particle, viral vectors (replicating and nonreplicating), nucleic acids (DNA or RNA), live attenuated virus, recombinant designed proteins and inactivated virus - are presently under various stages of expansion, and a small number of vaccine candidates have progressed into clinical phases. At the time of writing, three major pharmaceutical companies, namely Pfizer and Moderna, have their vaccines under mass production and administered to the public. This review aims to investigate the most critical vaccines developed for COVID-19 to date.

Rutin-loaded liquid crystalline nanoparticles attenuate oxidative stress in bronchial epithelial cells: a PCR validation.

Aim: In the present study, the inhibitory potential of rutin-loaded liquid crystalline nanoparticles (LCNs) on oxidative stress was determined in human bronchial epithelial cells (BEAS-2B) by analysing the expression levels of different antioxidant (NADPH quinine oxidoreductase-1 (NQO1); γ-glutamyl cysteine synthetase catalytic subunit (GCLC)) and pro-oxidant (NADPH oxidase (Nox)-4; Nox2B) genes. Results: Our findings revealed that the rutin-loaded LCNs inhibited the genes, namely Nox2B and Nox4, which caused oxidative stress. In addition, these nanoparticles demonstrated an upregulation in the expression of the antioxidant genes Gclc and Nqo-1 in a dose-dependent manner. Conclusion: The study indicates the promising potential of rutin-loaded LCNs as an effective treatment strategy in patients with high oxidant loads in various respiratory diseases.