“LONG COVID”—A hypothesis for understanding the biological basis and pharmacological treatment strategy

Pharmacology Research & Perspectives, Journal Year: 2022, Volume and Issue: 10(1)

Published: Jan. 13, 2022

Abstract Infection of humans with SARS‐CoV‐2 virus causes a disease known colloquially as “COVID‐19” symptoms ranging from asymptomatic to severe pneumonia. Initial pathology is due the binding ACE‐2 protein on endothelial cells lining blood vessels and entering these in order replicate. Viral replication oxidative stress elevated levels reactive oxygen species. Many (~60%) infected people appear have eliminated their body after 28 days resume normal activity. However, significant proportion (~40%) experience variety (loss smell and/or taste, fatigue, cough, aching pain, “brain fog,” insomnia, shortness breath, tachycardia) 12 weeks are diagnosed syndrome named “LONG COVID.” Longitudinal clinical studies group subjects who were been compared non‐infected matched subjects. A cohort can be identified by battery cytokine markers persistent, low level grade inflammation often self‐report two or more troubling symptoms. There no drug that will relieve effectively. It hypothesized drugs activate intracellular transcription factor, nuclear factor erythroid‐derived 2‐like 2 (NRF2) may increase expression enzymes synthesize antioxidant, glutathione quench free radicals causing stress. The hormone melatonin has an activator NRF2 relatively safe chemical for most ingest chronically. Thus, it option consideration re‐purposing COVID” experiencing depression, fog” but not tachycardia. Appropriately designed trials required evaluate melatonin.

Language: Английский

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Circadian Rhythms Disrupted by Light at Night and Mistimed Food Intake Alter Hormonal Rhythms and Metabolism

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3392 - 3392

Published: Feb. 8, 2023

Availability of artificial light and light-emitting devices have altered human temporal life, allowing 24-hour healthcare, commerce production, expanding social life around the clock. However, physiology behavior that evolved in context 24 h solar days are frequently perturbed by exposure to at night. This is particularly salient circadian rhythms, result endogenous biological clocks with a rhythm ~24 h. Circadian rhythms govern features behavior, set precisely primarily during day, though other factors, such as timing meals, can also affect rhythms. significantly affected night shift work because nocturnal light, electronic devices, shifts meals. Night workers increased risk for metabolic disorder, well several types cancer. Others who exposed or late mealtimes show disrupted cardiac disorders. It imperative understand how alter function develop strategies mitigate their negative effects. In this review, we provide an introduction physiological regulation homeostasis suprachiasmatic nucleus (SCN), SCN-mediated hormones display including melatonin glucocorticoids. Next, discuss circadian-gated processes sleep food intake, followed modern lighting disrupts molecular clock Lastly, identify disruptions metabolism increase susceptibility syndrome cardiovascular diseases, various harmful consequences associated on health.

Language: Английский

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Mitochondria Express Functional Signaling Ligand-Binding Receptors that Regulate their Biological Responses – the Novel Role of Mitochondria as Stress-Response Sentinels

Stem Cell Reviews and Reports, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Evidence accumulated mitochondria, as the "powerplants of cell," express several functional receptors for external ligands that modify their function and regulate cell biology. This review sheds new light on role these organelles in sensing stimuli to facilitate energy production cellular needs. is possible because mitochondria some membranes are responsible autonomous responses. not surprising given widely accepted hypothesis intracellular originated from prokaryotic ancestors fused with eukaryotic cells during early evolution. It has been reported estrogen, androgen, glucocorticoid, 5-hydroxytryptamine, melatonin, cannabinoid receptors. What intriguing recent evidence showing could also be directly regulated by active mediators complement (complosome) intrinsic purinergic signaling. Accordingly, they cleavage fragments (C5a C3a) well adenosine triphosphate (ATP), which, besides its crucial transferring cells, an important signaling molecule interacting P2X7 receptor expressed only surface but membrane. Based this, complosome emerge cooperating regulators reactive oxygen species (ROS) release activators pattern recognition Nlrp3 inflammasome. activation within beneficial "hormetic zone response" regulates metabolism, proliferation, migration, adaptation surrounding challenges microenvironment a favorable way.

Language: Английский

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The Effect of β-Carotene, Tocopherols and Ascorbic Acid as Anti-Oxidant Molecules on Human and Animal In Vitro/In Vivo Studies: A Review of Research Design and Analytical Techniques Used

Biomolecules, Journal Year: 2022, Volume and Issue: 12(8), P. 1087 - 1087

Published: Aug. 7, 2022

Prolonged elevated oxidative stress (OS) possesses negative effect on cell structure and functioning, is associated with the development of numerous disorders. Naturally occurred anti-oxidant compounds reduce in living organisms. In this review, antioxidant properties β-carotene, tocopherols ascorbic acid are presented based vitro, vivo populational studies. Firstly, environmental factors contributing to OS occurrence intracellular sources Reactive Oxygen Species (ROS) generation, as well ROS-mediated cellular degradation, introduced. Secondly, enzymatic non-enzymatic mechanism defence against development, presented. Furthermore, ROS-preventing mechanisms effectiveness anti-oxidants summarized, studies where different ROS-generating (oxidizing) agents used. Oxidative biomarkers, indicators level prevention by supplementation, a focus methods (spectrophotometric, fluorometric, chromatographic, immuno-enzymatic) their detection. Finally, application Raman spectroscopy imaging tool for monitoring (β-carotene, acid) metabolism, proposed. Literature data gathered suggest that possess potential mitigate various biological systems. Moreover, can be valuable technique study molecules

Language: Английский

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Polystyrene nanoplastic exposure induces excessive mitophagy by activating AMPK/ULK1 pathway in differentiated SH-SY5Y cells and dopaminergic neurons in vivo

Particle and Fibre Toxicology, Journal Year: 2023, Volume and Issue: 20(1)

Published: Nov. 22, 2023

Microplastics and nanoplastics (MNPs) are emerging environmental contaminants detected in human samples, have raised concerns regarding their potential risks to health, particularly neurotoxicity. This study aimed investigate the deleterious effects of polystyrene (PS-NPs, 50 nm) understand mechanisms inducing Parkinson's disease (PD)-like neurodegeneration, along with exploring preventive strategies.

Language: Английский

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Melatonin as an Anti-Aging Therapy for Age-Related Cardiovascular and Neurodegenerative Diseases

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: June 3, 2022

The concept of “aging” is defined as the set gradual and progressive changes in an organism that leads to increased risk weakness, disease, death. This process may occur at cellular organ level, well entire any living being. During aging, there a decrease biological functions ability adapt metabolic stress. General effects aging include mitochondrial, cellular, organic dysfunction, immune impairment or inflammaging, oxidative stress, cognitive cardiovascular alterations, among others. Therefore, one main harmful consequences development progression multiple diseases related these processes, especially central nervous system levels. Both neurodegenerative pathologies are highly disabling and, many cases, lethal. In this context, melatonin, endogenous compound naturally synthesized not only by pineal gland but also cell types, have key role modulation mechanisms associated with aging. Additionally, indoleamine therapeutic agent, which be administered exogenously high degree safety. For reason, melatonin could become attractive low-cost alternative for slowing processes its diseases, including disorders.

Language: Английский

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Aging-Related Ovarian Failure and Infertility: Melatonin to the Rescue

Antioxidants, Journal Year: 2023, Volume and Issue: 12(3), P. 695 - 695

Published: March 11, 2023

Aging has a major detrimental effect on the optimal function of ovary with changes in this organ preceding age-related deterioration other tissues, middle-aged shutdown leading to infertility. Reduced fertility and consequent inability conceive by women present-day societies who choose have children later life leads increased frustration. Melatonin is known anti-aging properties related its antioxidant anti-inflammatory actions. Its higher follicular fluid levels relative blood concentrations likely synthesis oocyte, granulosa, luteal cells suggest that it optimally positioned interfere age-associated ovary. Additionally, end female reproductive span coincides significant reduction endogenous melatonin levels. Thus, aims are review literature indicating production mitochondria oocytes, granulosa cells, identify multiple processes underlying ovary, especially late cessation span, summarize physiological molecular actions maintenance normal ovaries aging ovaries, integrate acquired information into an explanation for considering treatment Use supplemental may help preserve alleviate frustration delaying childbearing age, reduce necessity vitro fertilization–embryo transfer (IVF-ET) procedures, solve progressively increasing problem non-aging-related infertility throughout their span. While additional research needed fully understand effects supplementation potentially enhancing fertility, studies published date be promising option those struggling

Language: Английский

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The potential influence of melatonin on mitochondrial quality control: a review

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 11, 2024

Mitochondria are critical for cellular energetic metabolism, intracellular signaling orchestration and programmed death regulation. Therefore, mitochondrial dysfunction is associated with various pathogeneses. The maintenance of homeostasis functional recovery after injury coordinated by biogenesis, dynamics autophagy, which collectively referred to as quality control. There increasing evidence that mitochondria important targets melatonin exert protective effects under pathological conditions. Melatonin, an evolutionarily conserved tryptophan metabolite, can be synthesized, transported metabolized in mitochondria. In this review, we summarize the role damaged elimination energy supply regulating control, may provide new strategies clinical treatment mitochondria-related diseases.

Language: Английский

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The hidden link between circadian entropy and mental health disorders

Translational Psychiatry, Journal Year: 2022, Volume and Issue: 12(1)

Published: July 14, 2022

Abstract The high overlapping nature of various features across multiple mental health disorders suggests the existence common psychopathology factor(s) (p-factors) that mediate similar phenotypic presentations distinct but relatable disorders. In this perspective, we argue circadian rhythm disruption (CRD) is a underlying p-factor bridges within their age and sex contexts. We present analyze evidence from literature for critical roles rhythmicity plays in regulating mental, emotional, behavioral functions throughout lifespan. A review shows coarse CRD, such as sleep disruption, prevalent all at level etiological pathophysiological mechanisms clinical phenotypical manifestations. Finally, discuss subtle interplay CRD with relation to these different stages life. Our perspective highlights need shift investigations towards molecular levels, instance, by using spatiotemporal “omic” studies animal models identify complex causal relationships between

Language: Английский

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Role of Melatonin in the Management of Sleep and Circadian Disorders in the Context of Psychiatric Illness

Current Psychiatry Reports, Journal Year: 2022, Volume and Issue: 24(11), P. 623 - 634

Published: Oct. 13, 2022

Abstract Purpose of Review We present a review research on the role melatonin in management sleep and circadian disorders, stressing current overall view knowledge across psychiatric disorders. Recent Findings Dysregulation rhythms has been established several neurocognitive disorders for long. confirms this finding consistently The secretion schizophrenia is reduced due to smaller volume enlarged calcification pineal gland. On other hand, dysregulation bipolar disorder may be more dynamic caused by light-sensitive suppression delayed secretion. In both cases, exogenous seems indicated correct dysfunction. However, very limited number well-designed trials with exist evidence efficacy robust only autism, attention deficit hyperactivity (ADHD), This topic mainly not interest recent work objective parameters are few. Overall, studies reported that can effective improving such as onset latency, efficiency, quality. meta-analysis suggests optimal dosage dosing time might important maximize melatonin. base sufficient propose well-designed, larger inclusion outcome criteria. Based partly fragmentary information, we testing etiopathology later higher dosing, affective anxiety lower earlier Summary Melatonin promising correction abnormalities results its effect still few need accumulated. For use melatonin, it necessary consider appropriate administration time, depending individual abnormality rhythms.

Language: Английский

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