Purpose of review The circadian rhythms have a systemic impact on all aspects of physiology. Kidney diseases are associated with extremely high-cardiovascular mortality, related to chronic kidney disease-mineral bone disorder (CKD-MBD), involving bone, parathyroids and vascular calcification. Disruption of circadian rhythms may cause serious health problems, contributing to development of cardiovascular diseases, metabolic syndrome, cancer, organ fibrosis, osteopenia and aging. Evidence of disturbed circadian rhythms in CKD-MBD parameters and organs involved is emerging and will be discussed in this review. Recent findings Kidney injury induces unstable behavioral circadian rhythm. Potentially, uremic toxins may affect the master-pacemaker of circadian rhythm in hypothalamus. In CKD disturbances in the circadian rhythms of CKD-MBD plasma-parameters, activin A, fibroblast growth factor 23, parathyroid hormone, phosphate have been demonstrated. A molecular circadian clock is also expressed in peripheral tissues, involved in CKD-MBD; vasculature, parathyroids and bone. Expression of the core circadian clock genes in the different tissues is disrupted in CKD-MBD. Summary Disturbed circadian rhythms is a novel feature of CKD-MBD. There is a need to establish which specific input determines the phase of the local molecular clock and to characterize its regulation and deregulation in tissues involved in CKD-MBD. Finally, it is important to establish what are the implications for treatment including the potential applications for chronotherapy.

Circadian rhythms of mineral metabolism in chronic kidney disease-mineral bone disorder.

A large population, including people of all age groups, is suffering from chronic respiratory diseases worldwide. Asthma, chronic obstructive pulmonary disease, occupational lung diseases, cystic fibrosis, etc. are the most common of these diseases and are noncurable with conventional and currently available therapies. Nanotechnology is emerging as a great therapeutic promise in different spheres including drug delivery systems and is becoming the technology of choice nowadays. The administration of drugs via inhalation helps in avoiding the first-pass metabolism by targeted delivery to the affected site. It has been observed that there is a huge diversity in nanotechnology being used in pulmonary diseases, and thus safety assessment is a challenging as well as important task. The present review focuses on some of the major emerging nanotechnologies for chronic pulmonary diseases and includes some of the latest studies in the field of nanomedicines.

Emerging Nanotechnology in Chronic Respiratory Diseases

In this review, we have investigated how fasting promotes an adaptive cross-talk between different hormones and metabolic pathways to supply and meet the body's daily energy demands. We highlight in biochemical terms and mechanisms how fasting impacts four metabolic pathways-glycogenolysis, gluconeogenesis, amino acid oxidation, and fatty acid β-oxidation-that are actively engaged in the metabolism of carbohydrates, proteins, and lipids. Fasting results in reduced insulin secretion and increased glucagon and epinephrine release to prevent or stimulate metabolic reaction(s). Fasting stimulates glycogenolysis, amino acid and glucose oxidation, aminotransferase reactions in skeletal muscle, and promotes gluconeogenesis and urea production in the liver. In addition, fasting promotes gene expression of lipid metabolism in skeletal muscle, the synthesis of ketone bodies in the liver, and intracellular hormone-sensitive lipase activity in adipose tissue. Furthermore, the impact of fasting on reducing cellular damage by mitochondrial reactive oxygen species is discussed. Lastly, we briefly describe the impact of fasting on the four steps of pharmacokinetics-the absorption, distribution, metabolism, and excretion of a few select drugs-with an emphasis on the elimination of drugs related to the cytochrome-P450 family of enzymes.

The Impact of Fasting on Major Metabolic Pathways of Macronutrients and Pharmacokinetics Steps of Drugs

The circadian clock is a regulatory system, with a periodicity of approximately 24 h, that generates rhythmic changes in many physiological processes. Increasing evidence links chronodisruption with aberrant functionality in clock gene expression, resulting in multiple diseases, including cancer. In this context, tumor cells have an altered circadian machinery compared to normal cells, which deregulates the cell cycle, repair mechanisms, energy metabolism and other processes. Melatonin is the main hormone produced by the pineal gland, whose production and secretion oscillates in accordance with the light:dark cycle. In addition, melatonin regulates the expression of clock genes, including those in cancer cells, which could play a key role in the numerous oncostatic effects of this hormone. This review aims to describe and clarify the role of clock genes in cancer, as well as the possible mechanisms of the action of melatonin through which it regulates the expression of the tumor’s circadian machinery, in order to propose future anti-neoplastic clinical treatments.

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Role of Melatonin in Cancer: Effect on Clock Genes

BACKGROUND Asthma is a common ailment with a larger circadian difference. Nocturnal Asthma (NA) is an inconstant exacerbation of asthmatic condition related to the rise in warning sign during the night time and there is a need for its treatment addressing air route alertness and decline in lung functions. These symptoms are linked to sleep or known as circadian events. Chronotherapeutics is a management system based on an in-vivo drug accessibility programmed to check the rhythms of ailment in a direction to improve the therapeutic outcomes by suppressing the side effects. This review aims to provide an overview of NA, chronotherapeutics for the treatment of NA, bilayer tablets, and advanced techniques involved in the fabrication of bilayer tablets. The review also discusses some of the related patents. METHODS Relevant literature about the latest developments and updated information related to NA, chronotherapeutics and bilayer tablets has been very widely searched on different biomedical literature programs such as Google, Web of Science, PubMed portals, etc. Bilayer tablet mediated chronotherapy has gained significant attention and consideration as it is developed and fabricated based on the body's circadian rhythm. Bilayer tablets can deliver the bioactive compounds at an appropriate time, place as well as amount and site. RESULTS Available literature advocated that the bilayer matrix tablet containing a single drug in the sustained release film and fast releasing film, may be beneficial for the chronic diseases like asthma, migraine, diabetes, hypertension and inflammation which usually require immediate as well as maintained therapeutic effect. CONCLUSION The application of nanotechnology in the arena of medicine will transform the diagnosis and treatment strategies of a wide range of diseases in the upcoming years. The findings of this review confirm the importance of bilayer tablet based chronotherapy in nocturnal asthma.

Ankit Saini

Papers

Bilayer tablet based chronotherapeutics in the management of nocturnal asthma: an overview.