The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 8, 2023

Life expectancy is increasing throughout the world and coincides with a rise in non-communicable diseases (NCDs), especially for metabolic disease that includes diabetes mellitus (DM) neurodegenerative disorders. The debilitating effects of disorders influence entire body significantly affect nervous system impacting greater than one billion people disability peripheral as well cognitive loss, now seventh leading cause death worldwide. Metabolic disorders, such DM, neurologic remain significant challenge treatment care individuals since present therapies may limit symptoms but do not halt overall progression. These clinical challenges to address interplay between warrant innovative strategies can focus upon underlying mechanisms aging-related oxidative stress, cell senescence, death. Programmed pathways involve autophagy, apoptosis, ferroptosis, pyroptosis play critical role oversee processes include insulin resistance, β-cell function, mitochondrial integrity, reactive oxygen species release, inflammatory activation. silent mating type information regulation 2 homolog 1

Язык: Английский

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Luteolin inhibits spike protein of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) binding to angiotensin‐converting enzyme 2

Phytotherapy Research, Год журнала: 2023, Номер 37(8), С. 3508 - 3521

Опубликована: Май 11, 2023

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes disease 2019 (COVID‐19), a illness that poses serious threat to global public health. In an essential step during infection, SARS‐CoV‐2 uses the receptor‐binding domain (RBD) of spike (S) protein engage with angiotensin‐converting enzyme (ACE2) in host cells. Chinese herbal medicines and their active components exhibit antiviral activity, luteolin being flavonoid can significantly inhibit SARS‐CoV infection. However, whether it block interaction between S‐protein RBD ACE2 has not yet been elucidated. Here, we investigated effects on binding ACE2. By employing competitive assay vitro, found blocked IC50 values 0.61 mM, which was confirmed by neutralized infection pseudovirus vivo. A surface plasmon resonance‐based competition revealed affects receptor. Molecular docking performed predict sites RBD‐ACE2 complex. The were defined based published literature, might interfere mixture at residues including LYS353, ASP30, TYR83 cellular receptor GLY496, GLN498, TYR505, LEU455, GLN493, GLU484 RBD. These may together form attractive charges destroy stable RBD‐ACE2. Luteolin also inhibits protein‐induced platelet spreading, thereby inhibiting Our results are first provide evidence is anti‐SARS‐CoV‐2 agent associated interference viral interactions.

Язык: Английский

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Mast cells in the autonomic nervous system and potential role in disorders with dysautonomia and neuroinflammation

Annals of Allergy Asthma & Immunology, Год журнала: 2023, Номер 132(4), С. 440 - 454

Опубликована: Ноя. 10, 2023

Mast cells (MC) are ubiquitous in the body, and they critical for not only allergic diseases but also immunity inflammation, including having potential involvement pathophysiology of dysautonomias neuroinflammatory disorders. MC located perivascularly close to nerve endings sites such as carotid bodies, heart, hypothalamus, pineal gland, adrenal gland that would allow them regulate be affected by autonomic nervous system (ANS). stimulated allergens many other triggers some from ANS can affect release neurosensitizing, proinflammatory, vasoactive mediators. Hence, may able homeostatic functions seem dysfunctional conditions, postural orthostatic tachycardia syndrome, autism spectrum disorder, myalgic encephalomyelitis/chronic fatigue Long-COVID syndrome. The evidence indicates there is a possible association between these conditions associated with activation. There no effective treatment any form than minimizing symptoms. Given ways could activated numerous mediators released, it important develop inhibit stimulation ANS-relevant

Язык: Английский

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The emerging pandemic recent: SARS-CoV-2

Life Cycle, Год журнала: 2023, Номер 3

Опубликована: Янв. 22, 2023

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome 2 (SARS-CoV-2), induces coughing, vomiting, or fever. occurrence, duration, and severity of these symptoms vary from person to person, which makes the COVID-19 infection ranging those a mild cold death in cases. cause differences can be found individual characteristics patient. Age, former diseases patient, they medications took such characteristics. As SARS-CoV-2 affects lung, related lung as chronic obstructive pulmonary disease, cancer, cystic fibrosis, moderate asthma, hypertension, embolism are especially more dangerous human body when infected SARS-CoV-2. In this paper, through various methods including comparing mutant viruses subunits COVID-19, we aimed describe risk factors deterioration strain during pandemic.

Язык: Английский

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Possible Role of Fibrinaloid Microclots in Postural Orthostatic Tachycardia Syndrome (POTS): Focus on Long COVID

Journal of Personalized Medicine, Год журнала: 2024, Номер 14(2), С. 170 - 170

Опубликована: Янв. 31, 2024

Postural orthostatic tachycardia syndrome (POTS) is a common accompaniment of variety chronic, inflammatory diseases, including long COVID, as are small, insoluble, 'fibrinaloid' microclots. We here develop the argument, with accompanying evidence, that fibrinaloid microclots, through their ability to block flow blood microcapillaries and thus cause tissue hypoxia, not simply correlated but in fact, by preceding it, may be chief intermediary POTS, which body's exaggerated 'physiological' response hypoxia. Similar reasoning accounts for symptoms bundled under term 'fatigue'. Amyloids known membrane disruptors, when targets nerve membranes, this can explain neurotoxicity hence autonomic nervous system dysfunction contributes POTS. Taken together view, we indicate microclots serve link POTS fatigue COVID manner at once both mechanistic explanatory. This has clear implications treatment such diseases.

Язык: Английский

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