Recent Advances in Chronotherapy Targeting Respiratory Diseases

Paudel, Keshav Raj; Jha, Saurav Kumar; Allam, Venkata Sita Rama Raju; Prasher, Parteek; Gupta, Piyush Kumar; Bhattacharjee, Rahul; Jha, Niraj Kumar; Vishwas, Sukriti; Singh, Sachin Kumar; Shrestha, Jesus; Imran, Mohammad; Panth, Nisha; Chellappan, Dinesh Kumar; Warkiani, Majid Ebrahimi; Hansbro, Philip M.; Dua, Kamal

doi:10.3390/pharmaceutics13122008

Cited by 16 publications

(7 citation statements)

References 119 publications

(132 reference statements)

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“…Our pharmacogenetic analysis of REGs may guide future chronotherapy for headaches. One aspect of chronotherapy is time‐dependent medication delivery: This has been adopted in the treatment of hypertension, 83 asthma, 84 and other disorders, 36 but it has not been extensively investigated for primary headaches. For neurodegenerative disorders, chronotherapy aims to improve proteostasis from CCGs 85 ; along similar lines for headache, it would be sensible to time agonists at the trough of protein expression and antagonists at the peak.…”

Section: Discussionmentioning

confidence: 99%

Regulation of headache response and transcriptomic network by the trigeminal ganglion clock

Han,

Lim,

Koike

et al. 2024

Headache

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ObjectiveTo characterize the circadian features of the trigeminal ganglion in a mouse model of headache.BackgroundSeveral headache disorders, such as migraine and cluster headache, are known to exhibit distinct circadian rhythms of attacks. The circadian basis for these rhythmic pain responses, however, remains poorly understood.MethodsWe examined trigeminal ganglion ex vivo and single‐cell cultures from Per2::LucSV reporter mice and performed immunohistochemistry. Circadian behavior and transcriptomics were investigated using a novel combination of trigeminovascular and circadian models: a nitroglycerin mouse headache model with mechanical thresholds measured every 6 h, and trigeminal ganglion RNA sequencing measured every 4 h for 24 h. Finally, we performed pharmacogenomic analysis of gene targets for migraine, cluster headache, and trigeminal neuralgia treatments as well as trigeminal ganglion neuropeptides; this information was cross‐referenced with our cycling genes from RNA sequencing data to identify potential targets for chronotherapy.ResultsThe trigeminal ganglion demonstrates strong circadian rhythms in both ex vivo and single‐cell cultures, with core circadian proteins found in both neuronal and non‐neuronal cells. Using our novel behavioral model, we showed that nitroglycerin‐treated mice display circadian rhythms of pain sensitivity which were abolished in arrhythmic Per1/2 double knockout mice. Furthermore, RNA‐sequencing analysis of the trigeminal ganglion revealed 466 genes that displayed circadian oscillations in the control group, including core clock genes and clock‐regulated pain neurotransmitters. In the nitroglycerin group, we observed a profound circadian reprogramming of gene expression, as 331 of circadian genes in the control group lost rhythm and another 584 genes gained rhythm. Finally, pharmacogenetics analysis identified 10 genes in our trigeminal ganglion circadian transcriptome that encode target proteins of current medications used to treat migraine, cluster headache, or trigeminal neuralgia.ConclusionOur study unveiled robust circadian rhythms in the trigeminal ganglion at the behavioral, transcriptomic, and pharmacogenetic levels. These results support a fundamental role of the clock in pain pathophysiology.Plain Language SummarySeveral headache diseases, such as migraine and cluster headache, have headaches that occur at the same time each day. We learned that the trigeminal ganglion, an important pain structure in several headache diseases, has a 24‐hour cycle that might be related to this daily cycle of headaches. Our genetic analysis suggests that some medications may be more effective in treating migraine and cluster headache when taken at specific times of the day.

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Section: Discussionmentioning

confidence: 99%

Regulation of headache response and transcriptomic network by the trigeminal ganglion clock

Han,

Lim,

Koike

et al. 2024

Headache

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“…The inflammation biomarkers mentioned in the above OOC models can be measured by enzyme-linked immunosorbent assay (ELISA), quantitative polymerase chain reaction (qPCR), or immunofluorescence staining depending on the specific requirements of the OOC model. OOC models employ specific approaches with several of them outlined in Table . − …”

Section: Types Of Ooc Models For Nutraceutical Testingmentioning

confidence: 99%

“…OOC models can facilitate comparative assessments by providing a controlled and standardized platform. This comparative analysis can help make informed decisions regarding the selection and prioritization of nutraceutical candidates for further development. − Figure briefs the prerequisite considerations for the development of OOC models including cell types, chip dimension, infrastructure required, ECM, and microenvironment. − OOC models provide an opportunity to perform various toxicity tests specific to each organ system for nutraceuticals, i.e., acute toxicity assessments, chronic toxicity studies, genotoxicity evaluations, and immunotoxicity assays, by incorporating specific cell types and organ functionalities. The OOC platform can also be utilized for diagnostic purposes in nutraceutical research.…”

Section: Types Of Ooc Models For Nutraceutical Testingmentioning

confidence: 99%

Organ-on-Chip: Advancing Nutraceutical Testing for Improved Health Outcomes

Farooqi,

Kang,

Choi

2023

ACS Omega

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The recent global wave of organic food consumption and the vitality of nutraceuticals for human health benefits has driven the need for applying scientific methods for phytochemical testing. Advanced in vitro models with greater physiological relevance than conventional in vitro models are required to evaluate the potential benefits and toxicity of nutraceuticals. Organ-onchip (OOC) models have emerged as a promising alternative to traditional in vitro models and animal testing due to their ability to mimic organ pathophysiology. Numerous studies have demonstrated the effectiveness of OOC models in identifying pharmaceutically relevant compounds and accurately assessing compound-induced toxicity. This review examines the utility of traditional in vitro nutraceutical testing models and discusses the potential of OOC technology as a preclinical testing tool to examine the biomedical potential of nutraceuticals by reducing the need for animal testing. Exploring the capabilities of OOC models in carrying out plant-based bioactive compounds can significantly contribute to the authentication of nutraceuticals and drug discovery and validate phytochemicals medicinal characteristics. Overall, OOC models can facilitate a more systematic and efficient assessment of nutraceutical compounds while overcoming the limitations of current traditional in vitro models.

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“…6 With a dire need to address the growing global burden of respiratory diseases, rapid and efficient preclinical evaluation models are urgently required to fast-track the development of safe and efficacious new therapeutics and vaccines. 7,8 Some of these therapeutics target specific components of pulmonary disease such as inflammasomes, 9 interleukins (ILs), 10 matrix metalloproteinases (MMPs), 11 and mitochondrial dysfunction. 12 Drug development is an extensive, intricate, and expensive process, and has high attrition rates in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Advanced models for respiratory disease and drug studies

Shrestha

Paudel

Nazari

et al. 2023

Medicinal Research Reviews

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The global burden of respiratory diseases is enormous, with many millions of people suffering and dying prematurely every year. The global COVID‐19 pandemic witnessed recently, along with increased air pollution and wildfire events, increases the urgency of identifying the most effective therapeutic measures to combat these diseases even further. Despite increasing expenditure and extensive collaborative efforts to identify and develop the most effective and safe treatments, the failure rates of drugs evaluated in human clinical trials are high. To reverse these trends and minimize the cost of drug development, ineffective drug candidates must be eliminated as early as possible by employing new, efficient, and accurate preclinical screening approaches. Animal models have been the mainstay of pulmonary research as they recapitulate the complex physiological processes, Multiorgan interplay, disease phenotypes of disease, and the pharmacokinetic behavior of drugs. Recently, the use of advanced culture technologies such as organoids and lung‐on‐a‐chip models has gained increasing attention because of their potential to reproduce human diseased states and physiology, with clinically relevant responses to drugs and toxins. This review provides an overview of different animal models for studying respiratory diseases and evaluating drugs. We also highlight recent progress in cell culture technologies to advance integrated models and discuss current challenges and present future perspectives.

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Recent Advances in Chronotherapy Targeting Respiratory Diseases

Cited by 16 publications

References 119 publications

Regulation of headache response and transcriptomic network by the trigeminal ganglion clock

Regulation of headache response and transcriptomic network by the trigeminal ganglion clock

Organ-on-Chip: Advancing Nutraceutical Testing for Improved Health Outcomes

Advanced models for respiratory disease and drug studies

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