Unravelling the molecular mechanisms underlying chronic respiratory diseases for the development of novel therapeutics via in vitro experimental models

Tan, Ching Leng; Chan, Yinghan; Candasamy, Mayuren; Chellian, Jestin; Madheswaran, Thiagarajan; Sakthivel, Lakshmana Prabu; Patel, Vyoma; Chakraborty, Amlan; MacLoughlin, Ronan; Kumar, Deepak; Verma, Nitin; Malyla, Vamshikrishna; Gupta, Piyush Kumar; Jha, Niraj Kumar; Thangavelu, Lakshmi; Devkota, Hari Prasad; Bhatt, Shvetank; Prasher, Parteek; Gupta, Gaurav; Gulati, Monica; Singh, Sachin Kumar; Paudel, Keshav Raj; Hansbro, Philip M.; Oliver, Brian G.; Dua, Kamal; Chellappan, Dinesh Kumar

doi:10.1016/j.ejphar.2022.174821

Cited by 16 publications

(9 citation statements)

References 192 publications

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“…Various in vitro experimental models are commonly used to unravel the molecular mechanism associated with the progression of chronic respiratory disease [85]. Although we observed potent in vitro anti-cancer activity of BP-LCN formulations, there are several limitations to our study that are potential areas for future research.…”

Section: Discussionmentioning

confidence: 78%

Evaluation of the Cytotoxic Activity and Anti-Migratory Effect of Berberine–Phytantriol Liquid Crystalline Nanoparticle Formulation on Non-Small-Cell Lung Cancer In Vitro

et al. 2022

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Non-small-cell lung cancer (NSCLC) is the most common form of lung cancer, which is a leading cause of cancer-related deaths worldwide. Berberine is an isoquinoline alkaloid that is commercially available for use as a supplement for the treatment of diabetes and cardiovascular diseases. However, the therapeutic benefits of berberine are limited by its extremely low bioavailability and toxicity at higher doses. Increasing evidence suggests that the incorporation of drug compounds in liquid crystal nanoparticles provides a new platform for the safe, effective, stable, and controlled delivery of the drug molecules. This study aimed to formulate an optimized formulation of berberine–phytantriol-loaded liquid crystalline nanoparticles (BP-LCNs) and to investigate the in vitro anti-cancer activity in a human lung adenocarcinoma A549 cell line. The BP-LCN formulation possessing optimal characteristics that was used in this study had a favorable particle size and entrapment efficiency rate (75.31%) and a superior drug release profile. The potential mechanism of action of the formulation was determined by measuring the mRNA levels of the tumor-associated genes PTEN, P53, and KRT18 and the protein expression levels with a human oncology protein array. BP-LCNs decreased the proliferation, migration, and colony-forming activity of A549 cells in a dose-dependent manner by upregulating the mRNA expression of PTEN and P53 and downregulating the mRNA expression of KRT18. Similarly, BP-LCNs also decreased the expression of proteins related to cancer cell proliferation and migration. This study highlights the utility of phytantriol-based LCNs in incorporating drug molecules with low GI absorption and bioavailability to increase their pharmacological effectiveness and potency in NSCLC.

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Section: Discussionmentioning

confidence: 78%

Evaluation of the Cytotoxic Activity and Anti-Migratory Effect of Berberine–Phytantriol Liquid Crystalline Nanoparticle Formulation on Non-Small-Cell Lung Cancer In Vitro

et al. 2022

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“…This model has been used to study several chronic respiratory diseases, including but not limited to CF, viral infections and lung cancer. Airway organoids might thus represent the complex three-dimensional microenvironment of the airways by promoting differentiation of various cells types to physiologically resemble the diverse structural branching within the respiratory tract [ 120 , 121 , 122 ]. This model also allows for assessment of several channels’ function (not only CFTR but also other channels, such as ENaC and TMEM16A) and provides a complementary measurement of ion/fluid transport to ALI cultures.…”

Section: Preclinical In Vitro Modelsmentioning

confidence: 99%

Advances in Preclinical In Vitro Models for the Translation of Precision Medicine for Cystic Fibrosis

Silva¹,

Laselva

Lopes‐Pacheco

2022

JPM

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The development of preclinical in vitro models has provided significant progress to the studies of cystic fibrosis (CF), a frequently fatal monogenic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. Numerous cell lines were generated over the last 30 years and they have been instrumental not only in enhancing the understanding of CF pathological mechanisms but also in developing therapies targeting the underlying defects in CFTR mutations with further validation in patient-derived samples. Furthermore, recent advances toward precision medicine in CF have been made possible by optimizing protocols and establishing novel assays using human bronchial, nasal and rectal tissues, and by progressing from two-dimensional monocultures to more complex three-dimensional culture platforms. These models also enable to potentially predict clinical efficacy and responsiveness to CFTR modulator therapies at an individual level. In parallel, advanced systems, such as induced pluripotent stem cells and organ-on-a-chip, continue to be developed in order to more closely recapitulate human physiology for disease modeling and drug testing. In this review, we have highlighted novel and optimized cell models that are being used in CF research to develop novel CFTR-directed therapies (or alternative therapeutic interventions) and to expand the usage of existing modulator drugs to common and rare CF-causing mutations.

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“…The vital trilateral linkage between TLR, innate immunity, and lung disease is helpful to further understand the asthma pathophysiology (Patel et al 2022). As such, targeting senescence and inflammasomes in asthmatic (clinical study) or pre-clinical animal model (mice, rats) by advance drug delivery system such as nanotherapeutics could be a promising approach for the management of asthma (Devkota et al 2021b;Khursheed et al 2022;Paudel et al 2022a;Tan et al 2022). To study the pathophysiology of asthma and test various drugs in pre-clinical setting, experimental animal models of asthma are very useful.…”

Section: Introductionmentioning

confidence: 99%

Nutraceuticals and mitochondrial oxidative stress: bridging the gap in the management of bronchial asthma

Allam

Paudel

Gupta

et al. 2022

Environ Sci Pollut Res

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Asthma is a chronic inflammatory disease primarily characterized by inflammation and reversible bronchoconstriction. It is currently one of the leading causes of morbidity and mortality in the world. Oxidative stress further complicates the pathology of the disease. The current treatment strategies for asthma mainly involve the use of anti-inflammatory agents and bronchodilators. However, long-term usage of such medications is associated with severe adverse effects and complications. Hence, there is an urgent need to develop newer, novel, and safe treatment modalities for the management of asthma. This has therefore prompted further investigations and detailed research to identify and develop novel therapeutic interventions from potent untapped resources. This review focuses on the significance of oxidative stressors that are primarily derived from both mitochondrial and non-mitochondrial sources in initiating the clinical features of asthma. The review also discusses the biological scavenging system of the body and factors that may lead to its malfunction which could result in altered states. Furthermore, the review provides a detailed insight into the therapeutic role of nutraceuticals as an effective strategy to attenuate the deleterious effects of oxidative stress and may be used in the mitigation of the cardinal features of bronchial asthma.

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Unravelling the molecular mechanisms underlying chronic respiratory diseases for the development of novel therapeutics via in vitro experimental models

Cited by 16 publications

References 192 publications

Evaluation of the Cytotoxic Activity and Anti-Migratory Effect of Berberine–Phytantriol Liquid Crystalline Nanoparticle Formulation on Non-Small-Cell Lung Cancer In Vitro

Evaluation of the Cytotoxic Activity and Anti-Migratory Effect of Berberine–Phytantriol Liquid Crystalline Nanoparticle Formulation on Non-Small-Cell Lung Cancer In Vitro

Advances in Preclinical In Vitro Models for the Translation of Precision Medicine for Cystic Fibrosis

Nutraceuticals and mitochondrial oxidative stress: bridging the gap in the management of bronchial asthma

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