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.

Protein and peptide delivery to lungs by using advanced targeted drug delivery.

The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.

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.

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.

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.

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.

Quality of Glucosamine Products: Is it a Potential Reason for Inconsistent Clinical Outcomes in Osteoarthritis?

BACKGROUND: Clinical studies have reported inconsistent outcomes of glucosamine therapy in osteoarthritis patients. One possible reason could be the use of glucosamine products of varying quality. OBJECTIVE: Hence, this study aimed to assess the quality of glucosamine products marketed in Australia and India. This is the first study to investigate both the content and dissolution profiles of glucosamine products. METHOD: The content and dissolution analysis of Australian (n = 25 brands) and Indian (n = 21 brands) glucosamine products was performed according to the criteria specified in the United States Pharmacopoeia (USP). RESULTS: The quality analysis revealed that 16% and 18% of Australian brands, as well as 24% and 19% of Indian brands, did not fulfil the USP content and dissolution criteria, respectively. In approximately half of these cases, the glucosamine content was only slightly below (<3%) that specified by the USP and dissolution was achieved within 15 min after the duration specified by the USP. CONCLUSIONS: The majority of the brands did meet both the content and dissolution analysis criteria of the USP. The extent of deviation from the specified criteria for the other brands was probably insufficient to account for the significant variability in clinical effects. Hence, the study proposed that inter-patient pharmacokinetic variations in glucosamine could be another potential reason for inconsistent therapeutic effects.

The complex interplay between endoplasmic reticulum stress and the NLRP3 inflammasome: a potential therapeutic target for inflammatory disorders.

Inflammation is the result of a complex network of cellular and molecular interactions and mechanisms that facilitate immune protection against intrinsic and extrinsic stimuli, particularly pathogens, to maintain homeostasis and promote tissue healing. However, dysregulation in the immune system elicits excess/abnormal inflammation resulting in unintended tissue damage and causes major inflammatory diseases including asthma, chronic obstructive pulmonary disease, atherosclerosis, inflammatory bowel diseases, sarcoidosis and rheumatoid arthritis. It is now widely accepted that both endoplasmic reticulum (ER) stress and inflammasomes play critical roles in activating inflammatory signalling cascades. Notably, evidence is mounting for the involvement of ER stress in exacerbating inflammasome-induced inflammatory cascades, which may provide a new axis for therapeutic targeting in a range of inflammatory disorders. Here, we comprehensively review the roles, mechanisms and interactions of both ER stress and inflammasomes, as well as their interconnected relationships in inflammatory signalling cascades. We also discuss novel therapeutic strategies that are being developed to treat ER stress- and inflammasome-related inflammatory disorders.

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.

Variation in the pharmacokinetics of glucosamine in healthy individuals.

OBJECTIVES: Clinical trial data for the efficacy of glucosamine in OA are conflicting. Reportedly, Rotta-manufactured glucosamine products are more likely to be effective, and a possible explanation is greater bioavailability than other brands. Specifically, the aim was to compare the steady-state pharmacokinetics of Rotta- and non-Rotta-manufactured glucosamine products in healthy volunteers and examine the interindividual variability. METHODS: In a crossover design, healthy adult participants ingested 1500 mg/day of a Rotta (DONA powder sachets; imported by Mylan Health, Carole Park, QLD, Australia) and a non-Rotta (glucosamine sulphate 1500 mg one-a-day tablet; Blackmores, Warriewood, NSW, Australia) glucosamine product/brand individually for 6 days. Blood samples were collected immediately before and for 12 h after the ingestion of the last dose of each brand and analysed to determine plasma levels of glucosamine. The pharmacokinetic parameters at steady state [including the minimum (Css min) and maximum (Css max) plasma concentration of glucosamine, time to reach Css max post-dosing (Tss max) and area under the plasma concentration vs time curve (AUCss 0-12)] for each brand were calculated and statistically compared. RESULTS: Fourteen participants [mean age 35.5 years (s.d. 8.8)] were recruited (64.2% males). No significant differences were observed in the pharmacokinetic parameters between the two brands. However, for both brands, the coefficient of variation for Css min, Tss max and AUCss 0-12 exceeded 20%, indicating considerable differences in the parameters between participants. No significant association of the pharmacokinetic parameters was observed with various dosing- and participant-related variables. CONCLUSION: Substantial interindividual differences in the absorption and elimination of glucosamine could be a cause of variable clinical outcomes in OA. TRIAL REGISTRATION: The study was registered with the Australian New Zealand Clinical Trials Registry (http://www.ANZCTR.org.au/ACTRN12618000699268p.aspx), number ACTRN12618000699268p.

Emerging concepts and directed therapeutics for the management of asthma: regulating the regulators.

Asthma is a common, heterogeneous and serious disease, its prevalence has steadily risen in most parts of the world, and the condition is often inadequately controlled in many patients. Hence, there is a major need for new therapeutic approaches. Mild-to-moderate asthma is considered a T-helper cell type-2-mediated inflammatory disorder that develops due to abnormal immune responses to otherwise innocuous allergens. Prolonged exposure to allergens and persistent inflammation results in myofibroblast infiltration and airway remodelling with mucus hypersecretion, airway smooth muscle hypertrophy, and excess collagen deposition. The airways become hyper-responsive to provocation resulting in the characteristic wheezing and obstructed airflow experienced by patients. Extensive research has progressed the understanding of the underlying mechanisms and the development of new treatments for the management of asthma. Here, we review the basis of the disease, covering new areas such as the role of vascularisation and microRNAs, as well as associated potential therapeutic interventions utilising reports from animal and human studies. We also cover novel drug delivery strategies that are being developed to enhance therapeutic efficacy and patient compliance. Potential avenues to explore to improve the future of asthma management are highlighted.

Smoking and COVID-19: What we know so far.

The ongoing COVID-19 pandemic has placed a spotlight on infectious diseases and their associations with host factors and underlying conditions. New data on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus are entering the public domain at a rapid rate such that their distillation often lags behind. To minimise weak associations becoming perceived as established paradigms, it is imperative that methodologies and outputs from different studies are appropriately critiqued and compared. In this review, we examine recent data on a potential relationship between smoking and COVID-19. While the causal role of smoking has been firmly demonstrated in regard to lung cancer and chronic obstructive pulmonary disease, such associations have the benefit of decades' worth of multi-centre epidemiological and mechanistic data. From our analysis of the available studies to date, it appears that a relationship is emerging in regard to patients with a smoking history having a higher likelihood of developing more severe symptoms of COVID-19 disease than non-smokers. Data on whether COVID-19 has a greater incidence in smokers than non-smokers is thus far, contradictory and inconclusive. There is therefore a need for some caution to be exercised until further research has been conducted in a wider range of geographical settings with sufficient numbers of patients that have been carefully phenotyped in respect of smoking status and adequate statistical control for confounding factors.

Advanced drug delivery systems can assist in targeting coronavirus disease (COVID-19): A hypothesis.

The highly contagious coronavirus, which had already affected more than 2 million people in 210 countries, triggered a colossal economic crisis consequently resulting from measures adopted by various goverments to limit transmission. This has placed the lives of many people infected worldwide at great risk. Currently there are no established or validated treatments for COVID-19, that is approved worldwide. Nanocarriers may offer a wide range of applications that could be developed into risk-free approaches for successful therapeutic strategies that may lead to immunisation against the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) which is the primary causative organism that had led to the current COVID-19 pandemic. We address existing as well as emerging therapeutic and prophylactic approaches that may enable us to effectively combat this pandemic, and also may help to identify the key areas where nano-scientists can step in.

Streptococcus Thermophilus UASt-09 Upregulates Goblet Cell Activity in Colonic Epithelial Cells to a Greater Degree than other Probiotic Strains.

Probiotics have been widely used in maintaining gastrointestinal health, despite their actual mechanism remaining obscure. There are several hypotheses behind the beneficial effects of probiotics including the regulation of intestinal barrier function and improvement in immune responses in the gastrointestinal system. Multiple probiotics have been introduced in the market as effective dietary supplements in improving gastrointestinal integrity, but there are no or few studies that demonstrate their underlying mechanism. In the current study, we investigated and compared the efficacy of four probiotics (based on different bacterial species) in refining gastrointestinal health by improving mucus biosynthesis and intestinal immune response under in-vitro conditions. By analyzing the gene expression of mucus biosynthesis and intestinal immune response markers, we found that probiotic Streptococcus thermophilus UASt-09 showed promising potential in refining mucosal barrier and gastrointestinal health in human colonic epithelial cells, as compared to other commercial probiotics.