Life Sciences, Год журнала: 2021, Номер 278, С. 119597 - 119597
Опубликована: Май 8, 2021
Язык: Английский
European Journal of Pharmacology, Год журнала: 2021, Номер 907, С. 174365 - 174365
Опубликована: Июль 21, 2021
Язык: Английский
Процитировано
68
Life Sciences, Год журнала: 2022, Номер 301, С. 120612 - 120612
Опубликована: Май 4, 2022
Язык: Английский
Процитировано
53
Journal of Pineal Research, Год журнала: 2022, Номер 72(3)
Опубликована: Фев. 8, 2022
The evolutionarily ancient methoxyindoleamine, melatonin, has long perplexed investigators by its versatility of functions and mechanisms action, which include the regulation vertebrate pigmentation. Although first discovered through potent skin-lightening effects in amphibians, melatonin's role human skin hair follicle pigmentation impact on melanocyte physiology remain unclear. Synthesizing our limited current understanding this role, we specifically examine melanogenesis, oxidative biology, mitochondrial function, senescence, pigmentation-related clock gene activity, with emphasis skin, yet without ignoring instructive pointers from nonhuman species. Given strict dependence epithelial microenvironment, underscore that responses to melatonin are best interrogated a physiological tissue context. Current evidence suggests some metabolites inhibit both, melanogenesis (via reducing tyrosinase activity) proliferation stimulating membrane receptors (MT1, MT2). We discuss whether putative melanogenesis-inhibitory may occur via activation Nrf2-mediated PI3K/AKT signaling, estrogen receptor-mediated and/or melanocortin-1 receptor- cAMP-dependent melatonin-regulated changes peripheral genes regulate namely Bmal1 Per1. Melatonin also accumulate melanocytes where they exert net cyto- senescence-protective as well antioxidative operating free radical scavengers, synthesis activity ROS scavenging enzymes other antioxidants, promoting DNA repair, enhancing function. argue it is clinically biologically important definitively clarify cell culture-based observations translate into melatonin-induced pigmentary context, is, epidermis follicles ex vivo, confirmed clinical trial results. After defining major open questions field, close suggesting how begin answering them relevant, currently available preclinical situ research models.
Язык: Английский
Процитировано
39
Ageing Research Reviews, Год журнала: 2024, Номер 101, С. 102480 - 102480
Опубликована: Сен. 3, 2024
Mitochondria functionally degrade as neurons age. Degenerative changes cause inefficient oxidative phosphorylation (OXPHOS) and elevated electron leakage from the transport chain (ETC) promoting increased intramitochondrial generation of damaging reactive oxygen nitrogen species (ROS RNS). The associated progressive accumulation molecular damage causes an increasingly rapid decline in mitochondrial physiology contributing to aging. Melatonin, a multifunctional free radical scavenger indirect antioxidant, is synthesized matrix neurons. Melatonin reduces ETC elevates ATP production; it also detoxifies ROS/RNS via SIRT3/FOXO pathway upregulates activities superoxide dismutase 2 glutathione peroxidase. influences glucose processing by In neurogenerative diseases, often adopt Warburg-type metabolism which excludes pyruvate mitochondria causing reduced acetyl coenzyme A production. Acetyl supports citric acid cycle OXPHOS. Additionally, required co-substrate for arylalkylamine-N-acetyl transferase, rate limits melatonin synthesis; therefore, production diminished cells that experience making more vulnerable stress. Moreover, endogenously produced diminishes during aging, further increasing components. More normal preserved aging with supplementation.
Язык: Английский
Процитировано
11
Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)
Опубликована: Сен. 1, 2021
Abstract Surgery is the common treatment for early lung cancer with multiple pulmonary nodules, but it often accompanied by problem of significant malignancy other nodules in non-therapeutic areas. In this study, we found that a combined local radiofrequency ablation (RFA) and melatonin (MLT) greatly improved clinical outcomes patients minimizing function injury reducing probability malignant transformation or enlargement non-ablated Mechanically, as demonstrated an associated mouse tumor model, RFA not only effectively remove treated tumors also stimulate antitumor immunity, which could inhibit growth MLT enhanced RFA-stimulated NK activity exerted synergistic effects RFA. Transcriptomics proteomics analyses residual tissues revealed oxidative phosphorylation reduced acidification well hypoxia microenvironment, suggests reprogrammed metabolism after MLT. Analysis further depressed MAPK, NF-kappa B, Wnt, Hedgehog pathways upregulated P53 pathway tumors, was line inhibited growth. Combined reversed Warburg effect decreased malignancy. These findings thus provided innovative non-invasive strategy treating nodules. Trial registration: www.chictr.org.cn , identifier ChiCTR2100042695, http://www.chictr.org.cn/showproj.aspx?proj=120931 .
Язык: Английский
Процитировано
53
Cellular and Molecular Life Sciences, Год журнала: 2022, Номер 79(3)
Опубликована: Фев. 20, 2022
Abstract Numerous pharmaceutical drugs have been repurposed for use as treatments COVID-19 disease. These not consistently demonstrated high efficacy in preventing or treating this serious condition and all side effects to differing degrees. We encourage the continued consideration of antioxidant anti-inflammatory agent, melatonin, a countermeasure SARS-CoV-2 infection. More than 140 scientific publications identified melatonin likely useful agent treat Moreover, cited provide rationale prophylactic against condition. Melatonin has pan-antiviral it diminishes severity viral infections reduces death animals infected with numerous different viruses, including three coronaviruses. Network analyses, which compared used humans, also predicted that would be most effective preventing/treating COVID-19. Finally, when seriously patients were treated either alone combination other medications, these reduced infection, lowered rate, shortened duration hospitalization. Melatonin’s ability arrest may reduce health care exhaustion by limiting need Importantly, safety profile over wide range doses lacks significant toxicity. Some molecular processes resists infection are summarized. The authors believe available, potentially beneficial drugs, lack toxicity should pandemics such caused SARS-CoV-2.
Язык: Английский
Процитировано
35
Antioxidants, Год журнала: 2022, Номер 11(8), С. 1621 - 1621
Опубликована: Авг. 20, 2022
Reactive oxygen species (ROS) constitute a group of highly reactive molecules that have evolved as regulators important signaling pathways. In this context, tumor cells an altered redox balance compared to normal cells, which can be targeted antitumoral therapy by ROS levels and decreasing the capacity antioxidant system, leading programmed cell death. Melatonin is particular importance in development innovative cancer treatments due its oncostatic impact lack adverse effects. Despite being widely recognized pro-oxidant molecule mechanism action melatonin remains unclear, has hindered use clinical treatments. The current review aims describe clarify proposed inducing production order propose future anti-neoplastic applications.
Язык: Английский
Процитировано
33
Biomolecules, Год журнала: 2022, Номер 12(11), С. 1646 - 1646
Опубликована: Ноя. 7, 2022
Clinical sequelae and symptoms for a considerable number of COVID-19 patients can linger months beyond the acute stage SARS-CoV-2 infection, “long COVID”. Among long-term consequences cognitive issues (especially memory loss or “brain fog”), chronic fatigue, myalgia, muscular weakness resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are importance. Melatonin may be particularly effective at reducing signs infection due to its functions as an antioxidant, anti-inflammatory, immuno-modulatory agent. is also chronobiotic medication in treating delirium restoring circadian imbalance seen COVID intensive care unit. Additionally, cytoprotector, melatonin aids prevention several comorbidities, including diabetes, metabolic syndrome, ischemic non-ischemic cardiovascular diseases. This narrative review discusses application neuroprotective agent control deterioration (“brain fog”) pain ME/CFS syndrome-like documented long COVID. Further studies on therapeutic use neurological warranted.
Язык: Английский
Процитировано
30
Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 161, С. 114526 - 114526
Опубликована: Март 16, 2023
Cancer cells are usually featured by metabolic adaptations that facilitate their growth, invasion, and metastasis. Thus, reprogramming of intracellular energy metabolism is currently one the hotspots in field cancer research. Whereas aerobic glycolysis (known as Warburg effect) has long been considered a dominant form cells, emerging evidence indicates other forms, especially oxidative phosphorylation (OXPHOS), may play critical role at least some types cancer. Of note, women with syndromes (MetS), including obesity, hyperglycemia, dyslipidemia, hypertension, have an increased risk developing endometrial carcinoma (EC), suggesting close link between EC. Interestingly, preferences vary among EC cell types, particularly stem chemotherapy-resistant cells. Currently, it commonly accepted main provider while OXPHOS reduced or impaired. Moreover, agents specifically targeting and/or pathways can inhibit tumor growth promote chemosensitization. For example, metformin weight control not only reduce incidence but also improve prognosis patients. In this review, we comprehensively overview current in-depth understanding relationship provide up-to-date insights into development novel therapies for auxiliary treatment combination chemotherapy EC, those resistant to conventional chemotherapy.
Язык: Английский
Процитировано
21
International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(22), С. 12494 - 12494
Опубликована: Ноя. 19, 2021
Melatonin is synthesized in the pineal gland at night. Since melatonin produced mitochondria of all other cells a non-circadian manner, amount by less than 5% total. influences glucose metabolism cells. Many pathological adopt aerobic glycolysis (Warburg effect) which pyruvate excluded from and remains cytosol where it metabolized to lactate. The entrance into healthy allows be irreversibly decarboxylated dehydrogenase (PDH) acetyl coenzyme A (acetyl-CoA). exclusion prevents generation acetyl-CoA pyruvate. This relevant mitochondrial production, as required co-substrate/co-factor for synthesis. When PDH inhibited during or intracellular hypoxia, deficiency likely experiencing hypoxia with diminished level are supplemented receive another endogenous source (pineal-derived), convert more normal phenotype support transport mitochondria, thereby re-establishing healthier metabolic physiology.
Язык: Английский
Процитировано
38