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Article ; Online: Beyond Conventional Therapies: Molecular Dynamics of Alzheimer's Treatment through CLOCK/BMAL1 Interactions.

Haskologlu, Ismail Celil / Erdag, Emine / Sehirli, Ahmet Ozer / Uludag, Orhan / Abacioglu, Nurettin

2024

Abstract: Background: Alzheimer's Disease (AD) represents a neurodegenerative disorder characterized by cognitive and behavioral impairments significantly hindering social and occupational functioning. Melatonin, a hormone pivotal in regulating the body's ... ...

Abstract	Background: Alzheimer's Disease (AD) represents a neurodegenerative disorder characterized by cognitive and behavioral impairments significantly hindering social and occupational functioning. Melatonin, a hormone pivotal in regulating the body's intrinsic circadian rhythm, also acts as a catalyst in the breakdown of beta-amyloid deposits, offering a promising therapeutic approach for AD. The upregulation of Brain and Muscle ARNT-Like 1 (Bmal1) gene expression, stimulated by melatonin, emerges as a potential contributor to AD intervention. Current pharmacological interventions, such as FDA-approved cholinesterase inhibitors and the recently authorized monoclonal antibody, Lecanemab, are utilized in AD management. However, the connection between these medications and Bmal1 remains insufficiently explored. Objective: This study aims to investigate the molecular effects of FDA-endorsed drugs on the CLOCK: Bmal1 dimer. Furthermore, considering the interactions between melatonin and Bmal1, this research explores the potential synergistic efficacy of combining these pharmaceutical agents with melatonin for AD treatment. Methods: Using molecular docking and MM/PBSA methodologies, this research determines the binding affinities of drugs within the Bmal1 binding site, constructing interaction profiles. Results: The findings reveal that, among FDA-approved drugs, galanthamine and donepezil demonstrate notably similar binding energy values to melatonin, interacting within the Bmal1 binding site through analogous amino acid residues and functional groups. Conclusion: A novel therapeutic approach emerges, suggesting the combination of melatonin with Lecanemab as a monoclonal antibody therapy. Importantly, prior research has not explored the effects of FDA-approved drugs on Bmal1 expression or their potential for synergistic effects.
Language	English
Publishing date	2024-03-19
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2205170-3
ISSN	1875-5828 ; 1567-2050
ISSN (online)	1875-5828
ISSN	1567-2050
DOI	10.2174/0115672050301014240315065235
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Article ; Online: Daylight is critical to preserve 5-methoxytryptophol levels in suspected and confirmed COVID-19 patients.

Şehirli, Ahmet Özer / Sayıner, Serkan

Medical hypotheses

2021 Volume 147, Page(s) 110504

Abstract: Declared as a pandemic by the World Health Organization, COVID-19 causes damage to tissues with the cytokine storm. It even causes death in people who are fond of it. In this case, the role of the immune system is vital. In particular, the cycle of ... ...

Abstract	Declared as a pandemic by the World Health Organization, COVID-19 causes damage to tissues with the cytokine storm. It even causes death in people who are fond of it. In this case, the role of the immune system is vital. In particular, the cycle of melatonin and 5-methoxytryptophol released from the pineal hormone ensures that immunity continues for 24 h. While 5-MTX is active in sunlight, melatonin secretion increases in the dark at night. 5-MTX, like melatonin, has shown antioxidant and immunomodulatory properties in studies. Therefore, people who are sick and those who are not must strictly comply with the 24-h circadian rhythm during this period. We think that it is crucial in terms of being protected from the disease that we should carry out our activities according to the circadian rhythm.
MeSH term(s)	Antioxidants/metabolism ; COVID-19/blood ; COVID-19/physiopathology ; Circadian Rhythm ; Cytokine Release Syndrome/virology ; Humans ; Immune System ; Indoles/blood ; Indoles/chemistry ; Light ; Melatonin/blood ; Pineal Gland/metabolism ; Sunlight
Chemical Substances	Antioxidants ; Indoles ; indolamine (56480-48-9) ; methoxytryptophol (712-09-4) ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2021-01-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2021.110504
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Article ; Online: An

Erdag, Emine / Haskologlu, Ismail Celil / Mercan, Merve / Abacioglu, Nurettin / Sehirli, Ahmet Ozer

Chronobiology international

2023 Volume 40, Issue 10, Page(s) 1395–1403

Abstract: Chronobiology, which studies biological rhythms and their impacts on health, presents a potential avenue for treating amyotrophic lateral sclerosis. Clock gene-related therapies, focusing on genes responsible for regulating biological rhythms, may hold ... ...

Abstract	Chronobiology, which studies biological rhythms and their impacts on health, presents a potential avenue for treating amyotrophic lateral sclerosis. Clock gene-related therapies, focusing on genes responsible for regulating biological rhythms, may hold promise in the treatment. Among these clock genes, nuclear receptor subfamily 1 Group D member 1 (NR1D1) plays a vital role in neurodegenerative diseases. In this particular study, it was aimed to investigate the potential of FDA-approved drugs commonly used in amyotrophic lateral sclerosis treatment and melatonin, a hormone known for its role in regulating sleep-wake cycles, as ligands for clock gene-related therapy. The ligands were subjected to molecular docking and molecular dynamics simulation methods against the NR1D1 clock gene. These results suggested that combining melatonin with FDA-approved medications commonly used in the treatment might yield positive outcomes. This study provides preliminary data and lays the groundwork for future investigations involving
MeSH term(s)	Animals ; Humans ; Melatonin/pharmacology ; Circadian Rhythm/physiology ; Amyotrophic Lateral Sclerosis/drug therapy ; Molecular Docking Simulation ; Chronotherapy/methods ; Nuclear Receptor Subfamily 1, Group D, Member 1/genetics
Chemical Substances	Melatonin (JL5DK93RCL) ; NR1D1 protein, human ; Nuclear Receptor Subfamily 1, Group D, Member 1
Language	English
Publishing date	2023-11-03
Publishing country	England
Document type	Journal Article
ZDB-ID	998996-1
ISSN	1525-6073 ; 0742-0528
ISSN (online)	1525-6073
ISSN	0742-0528
DOI	10.1080/07420528.2023.2265476
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Article: Could Ambroxol reduce cytokines in hepatic ischemia-reperfusion injury in rats?

Gultekin, Cagri / Sehirli, Ahmet Ozer / Cetinel, Sule / Sayiner, Serkan

Bratislavske lekarske listy

2022 Volume 123, Issue 5, Page(s) 381–384

Abstract: Objectives: The aim of the study is to examine the effect of Ambroxol on TNF-α and IL-1β released after liver ischemia-reperfusion injury.: Background: Many drugs are being tried to reduce ischemia-reperfusion injury, which is life threating problem ... ...

Abstract	Objectives: The aim of the study is to examine the effect of Ambroxol on TNF-α and IL-1β released after liver ischemia-reperfusion injury. Background: Many drugs are being tried to reduce ischemia-reperfusion injury, which is life threating problem after many liver surgeries. In this study, it was investigated whether Ambroxol reduces the release of pro-inflammatory cytokines released after liver ischemia-reperfusion injury. Methods: Twenty-four Wistar albino rats were divided into 3 groups as Control (CTR; n=8), hepatic ischemia reperfusion (H-IR; n=8) and hepatic ischemia reperfusion+Ambroxol (H-IR+AMB; n=8). In H-IR+AMB group, Ambroxol (30 mg/kg) was administered orally 30 minutes before ischemia period. In H-IR and H-IR+AMB groups underwent 45 minutes of hepatic ischemia followed by a 60-minute reperfusion period. After reperfusion period, tissue and blood samples were collected from euthanised animals. ALT, AST, ALP, LDH, TNF-α, IL-1β concentrations and liver tissues were evaluated. Results: Serum ALT, ALP, AST, LDH, TNF-α and IL-1β values were lower in the H-IR+AMB group compared to the H-IR group. In the histopathological examination, hepatocyte degeneration and congestion in the H-IR group were higher than in the H-IR+AMB group. Conclusion: It was determined that Ambroxol treatment suppressed the production of pro-inflammatory cytokines TNF-α and IL-1β in rats undergoing hepatic ischemia reperfusion (Tab. 1, Fig. 2, Ref. 28).
MeSH term(s)	Ambroxol/pharmacology ; Ambroxol/therapeutic use ; Animals ; Cytokines ; Ischemia/pathology ; Liver ; Liver Diseases ; Rats ; Rats, Wistar ; Reperfusion Injury/drug therapy ; Tumor Necrosis Factor-alpha
Chemical Substances	Cytokines ; Tumor Necrosis Factor-alpha ; Ambroxol (200168S0CL)
Language	English
Publishing date	2022-04-14
Publishing country	Slovakia
Document type	Journal Article
ZDB-ID	127421-1
ISSN	0006-9248
ISSN	0006-9248
DOI	10.4149/BLL_2022_060
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Article ; Online: Possible cytoprotective mechanisms of oxytocin against 5-fluorouracil-induced gastrointestinal mucositis.

Chukwunyere, Ugochukwu / Mercan, Merve / Sehirli, Ahmet Ozer / Abacioglu, Nurettin

Molecular biology reports

2022 Volume 49, Issue 5, Page(s) 4055–4059

Abstract: Gastrointestinal mucositis is a common and dose-limiting side effect characterized by ulcerative lesions in the mucosa of the digestive tract in patients receiving anticancer drugs such as 5-fluorouracil (5-FU), a potent antineoplastic drug. Several ... ...

Abstract	Gastrointestinal mucositis is a common and dose-limiting side effect characterized by ulcerative lesions in the mucosa of the digestive tract in patients receiving anticancer drugs such as 5-fluorouracil (5-FU), a potent antineoplastic drug. Several protocols have reported the efficacy of therapeutic interventions to prevent this side effect, although complete success has not yet been achieved and mucositis remains one of the most serious complications associated with 5-FU therapy. Oxytocin, a well-known antistress agent, has been reported to have comparable effects to ranitidine. Previous studies have shown that oxytocin inhibits gastric acid secretion and the expression of proinflammatory cytokines in rats. If oxytocin can reduce stress-induced ulcers via antioxidant, antiapoptotic, and anti-inflammatory pathways, then it may have a dose-dependent effect on gastrointestinal mucositis caused by 5-FU.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/pharmacology ; Antineoplastic Agents/pharmacology ; Fluorouracil/adverse effects ; Humans ; Intestinal Mucosa/metabolism ; Mucositis/chemically induced ; Mucositis/drug therapy ; Mucositis/pathology ; Oxytocin/metabolism ; Oxytocin/pharmacology ; Oxytocin/therapeutic use ; Rats
Chemical Substances	Anti-Inflammatory Agents ; Antineoplastic Agents ; Oxytocin (50-56-6) ; Fluorouracil (U3P01618RT)
Language	English
Publishing date	2022-04-26
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-022-07384-3
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Article ; Online: COVID-19-related arrhythmias and the possible effects of ranolazine.

Chukwunyere, Ugochukwu / Sehirli, Ahmet Ozer / Abacioglu, Nurettin

Medical hypotheses

2021 Volume 149, Page(s) 110545

Abstract: The COVID-19 pandemic has become a burden to the global healthcare community. Despite the severity of the complications associated with COVID-19, no antiviral agent is yet available for the treatment of this disease. Several studies have reported ... ...

Abstract	The COVID-19 pandemic has become a burden to the global healthcare community. Despite the severity of the complications associated with COVID-19, no antiviral agent is yet available for the treatment of this disease. Several studies have reported arrhythmias as one of the numerous manifestations associated with COVID-19 infection. Clinicians use different therapeutic agents in the management of COVID-19 patients with arrhythmias, apart from ranolazine; however, some of these drugs are administered with caution because of their significant side effects. In this study, we reviewed the potential antiarrhythmic effects of ranolazine in the management of cardiac arrhythmias associated with COVID-19. Ranolazine is a second-line drug approved for the treatment of chronic stable angina pectoris. Previous studies have shown that ranolazine produces its beneficial cardiac effects without any significant impact on the body's hemodynamics; hence, blood pressure is not altered. Due to its reduced side effects, ranolazine may be more effective than other drugs in producing the desired relief from COVID-19 related arrhythmias, since it produces its antiarrhythmic effect by modulating sodium, potassium and calcium channels, and suppressing cytokine expression.
MeSH term(s)	Action Potentials ; Angina, Stable/complications ; Anti-Arrhythmia Agents/therapeutic use ; Arrhythmias, Cardiac/complications ; Arrhythmias, Cardiac/prevention & control ; COVID-19/complications ; COVID-19/drug therapy ; Cytokines/metabolism ; Hemodynamics ; Humans ; Inflammation ; Potassium Channels/metabolism ; Ranolazine/therapeutic use ; Sodium Channel Blockers/therapeutic use
Chemical Substances	Anti-Arrhythmia Agents ; Cytokines ; Potassium Channels ; Sodium Channel Blockers ; Ranolazine (A6IEZ5M406)
Language	English
Publishing date	2021-02-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2021.110545
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Article: The Role of the SLC Transporters Protein in the Neurodegenerative Disorders.

Ayka, Asli / Şehirli, Ahmet Özer

Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology

2020 Volume 18, Issue 2, Page(s) 174–187

Abstract: The solute carrier (SLC) superfamily is one of the major sub-groups of membrane proteins in mammalian cells. The solute carrier proteins include more than 400 different membrane-spanning solute carriers organized with 65 families in the human. In solute ... ...

Abstract	The solute carrier (SLC) superfamily is one of the major sub-groups of membrane proteins in mammalian cells. The solute carrier proteins include more than 400 different membrane-spanning solute carriers organized with 65 families in the human. In solute carrier family neurons, neurotransmitter is considered to be a pharmacological target of neuropsychiatric drugs because of their important role in the recovery of neurotransmitters such as GABA, glutamate, serotonin, dopamine and noradrenaline and regulation of their concentration in synaptic regions. Therefore, solute carrier transporters play vital and different roles in neurodegenerative disorders. In this article, the role of solute carrier transporters in neurodegenerative disorders such as Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, Parkinson's diseases, depression, post-traumatic stress disorder, dementia, schizophrenia, and Epilepsy reviewed and discussed to see how defects or absences in SLC transporter cause neurodegenerative disorders. In this review, we try to summarize what is known about solute carriers with respect to brain distribution and expression. The review summarizes current knowledge on the roles of solute carrier transporters in neurodegenerative disorders.
Language	English
Publishing date	2020-04-24
Publishing country	Korea (South)
Document type	Journal Article ; Review
ZDB-ID	2211550-X
ISSN	1738-1088
ISSN	1738-1088
DOI	10.9758/cpn.2020.18.2.174
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Article ; Online: Role of Melatonin in Angiotensin and Aging.

Sehirli, Ahmet Ozer / Sayıner, Serkan / Chukwunyere, Ugochukwu / Serakinci, Nedime

Molecules (Basel, Switzerland)

2021 Volume 26, Issue 15

Abstract: The cellular utilization of oxygen leads to the generation of free radicals in organisms. The accumulation of these free radicals contributes significantly to aging and several age-related diseases. Angiotensin II can contribute to DNA damage through ... ...

Abstract	The cellular utilization of oxygen leads to the generation of free radicals in organisms. The accumulation of these free radicals contributes significantly to aging and several age-related diseases. Angiotensin II can contribute to DNA damage through oxidative stress by activating the NAD(P)H oxidase pathway, which in turn results in the production of reactive oxygen species. This radical oxygen-containing molecule has been linked to aging and several age-related disorders, including renal damage. Considering the role of angiotensin in aging, melatonin might relieve angiotensin-II-induced stress by enhancing the mitochondrial calcium uptake 1 pathway, which is crucial in preventing the mitochondrial calcium overload that may trigger increased production of reactive oxygen species and oxidative stress. This review highlights the role and importance of melatonin together with angiotensin in aging and age-related diseases.
MeSH term(s)	Aging/genetics ; Aging/metabolism ; Angiotensin II/genetics ; Antioxidants/metabolism ; DNA Damage/drug effects ; Free Radicals/chemistry ; Humans ; Melatonin/genetics ; Mitochondria/metabolism ; Oxidative Stress/genetics ; Reactive Oxygen Species/metabolism
Chemical Substances	Antioxidants ; Free Radicals ; Reactive Oxygen Species ; Angiotensin II (11128-99-7) ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2021-07-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules26154666
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Article ; Online: Role of melatonin in the treatment of COVID-19; as an adjuvant through cluster differentiation 147 (CD147).

Sehirli, Ahmet Ozer / Sayiner, Serkan / Serakinci, Nedime

Molecular biology reports

2020 Volume 47, Issue 10, Page(s) 8229–8233

Abstract: COVID-19 caused by the SARS-CoV-2 outbreak quickly has turned into a pandemic. However, no specific antiviral agent is yet available. In this communication, we aimed to evaluate the significance of CD147 protein and the potential protective effect of ... ...

Abstract	COVID-19 caused by the SARS-CoV-2 outbreak quickly has turned into a pandemic. However, no specific antiviral agent is yet available. In this communication, we aimed to evaluate the significance of CD147 protein and the potential protective effect of melatonin that is mediated by this protein in COVID-19. CD147 is a glycoprotein that is responsible for the cytokine storm in the lungs through the mediation of viral invasion. Melatonin use previously was shown to reduce cardiac damage by blocking the CD147 activity. Hence, melatonin, a safe drug, may prevent severe symptoms, reduce symptom severity and the adverse effects of the other antiviral drugs in COVID-19 patients. In conclusion, the use of melatonin, which is reduced in the elderly and immune-compromised patients, should be considered as an adjuvant through its CD147 suppressor and immunomodulatory effect.
MeSH term(s)	Adjuvants, Pharmaceutic/therapeutic use ; Animals ; Antioxidants/metabolism ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Basigin/antagonists & inhibitors ; Basigin/metabolism ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/metabolism ; Humans ; Immune System/drug effects ; Melatonin/pharmacology ; Melatonin/therapeutic use ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/metabolism ; Signal Transduction/drug effects
Chemical Substances	Adjuvants, Pharmaceutic ; Antioxidants ; Antiviral Agents ; BSG protein, human ; Basigin (136894-56-9) ; Melatonin (JL5DK93RCL)
Keywords	covid19
Language	English
Publishing date	2020-09-12
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-020-05830-8
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Article ; Online: Melatonin and REGN-CoV2 combination as a vaccine adjuvant for Omicron variant of SARS-CoV-2.

Haskologlu, Ismail Celil / Erdag, Emine / Sayiner, Serkan / Abacioglu, Nurettin / Sehirli, Ahmet Ozer

Molecular biology reports

2022 Volume 49, Issue 5, Page(s) 4061–4068

Abstract: The omicron variant (B.529) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in late 2021, caused panic worldwide due to its contagiousness and multiple mutations in the spike protein compared to the Delta variant (B.617. ...

Abstract	The omicron variant (B.529) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in late 2021, caused panic worldwide due to its contagiousness and multiple mutations in the spike protein compared to the Delta variant (B.617.2). There is currently no specific antiviral available to treat Coronavirus disease 2019 (COVID-19). However, studies on neutralizing monoclonal antibodies (mAb) developed to fight COVID-19 are growing and gaining traction. REGN-COV2 (Regeneron or imdevimab-casirivimab combination), which has been shown in recent studies to be less affected by Omicron's RBD (receptor binding domain) mutations among other mAb cocktails, plays an important role in adjuvant therapy against COVID-19. On the other hand, it is known that melatonin, which has antioxidant and immunomodulatory effects, can prevent a possible cytokine storm, and other severe symptoms that may develop in the event of viral invasion. Along with all these findings, we believe it is crucial to evaluate the use of melatonin with REGN-COV2, a cocktail of mAbs, as an adjuvant in the treatment and prevention of COVID-19, particularly in immunocompromised and elderly patients.
MeSH term(s)	Adjuvants, Vaccine ; Aged ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibodies, Neutralizing ; Antineoplastic Agents, Immunological ; COVID-19/drug therapy ; Drug Combinations ; Humans ; Melatonin/pharmacology ; Melatonin/therapeutic use ; SARS-CoV-2
Chemical Substances	Adjuvants, Vaccine ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antibodies, Neutralizing ; Antineoplastic Agents, Immunological ; Drug Combinations ; casirivimab and imdevimab drug combination ; imdevimab (2Z3DQD2JHM) ; casirivimab (J0FI6WE1QN) ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2022-04-07
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-022-07419-9
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