Review
Chemistry, Medicinal
Yueqin Feng, Xiaowen Jiang, Wenwu Liu, Hongyuan Lu
Summary: This review focuses on the anatomical localization, physiological function, and roles in neurological disorders of the melatonin MT2 receptor in the hippocampus. It also provides a comprehensive review of MT2 receptor ligands used in psychopharmacology and other MT2-selective ligands over recent years, as well as an outlook on future research for selective MT2 receptor drug candidates.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Nedjma Labani, Florence Gbahou, Marc Noblet, Bernard Masri, Olivier Broussaud, Jianfeng Liu, Ralf Jockers
Summary: This study examined the effects of 25 commercial plant extracts on cellular assays and found that Ex18, an extract from Pistacia vera dried fruits, had potent effects on melatonin receptor expressing cells. The extract was found to have high levels of endogenous melatonin and contained additional active principles that enhanced the effects of melatonin. These findings may have therapeutic potential.
Article
Neurosciences
Nana Gao, Wei Zheng, Tiliwaerde Murezati, Wei Gu, Xiaorong Li, Zengliang Jin
Summary: The study suggests that GW117 functions as a serotonin 2C (5-HT2C) receptor antagonist and melatonin type 1 and 2 (MT1/MT2) receptor agonist, showing evident antidepressant and anxiolytic effects.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Article
Endocrinology & Metabolism
Luca Posa, Danilo De Gregorio, Martha Lopez-Canul, Qianzi He, Emmanuel Darcq, Laura Rullo, Leora Pearl-Dowler, Livio Luongo, Sanzio Candeletti, Patrizia Romualdi, Brigitte Lina Kieffer, Gabriella Gobbi
Summary: In this study, the relationship between melatonin MT2 receptors and the opioid system in neuropathic pain was investigated. The results showed that the antiallodynic effects of a melatonin MT2 agonist required the activation of mu opioid receptors (MORs), but not delta opioid receptors (DORs). Electrophysiological recordings and immunohistochemistry studies revealed that the interaction between MORs and MT2 receptors within a neuronal circuit in the brain was responsible for the analgesic effects of the MT2 agonist.
JOURNAL OF PINEAL RESEARCH
(2022)
Article
Cell Biology
Junqiang Zhang, Yuan Fang, Dongdong Tang, Xingyu Xu, Xiaoqian Zhu, Shusheng Wu, Hui Yu, Huiru Cheng, Ting Luo, Qunshan Shen, Yang Gao, Cong Ma, Yajing Liu, Zhaolian Wei, Xiaoyu Chen, Fangbiao Tao, Xiaojin He, Yunxia Cao
Summary: This study explores the protective effect and molecular mechanism of melatonin in cisplatin-induced oxidative stress in testicular tissue and Leydig cells. The results show that melatonin reduces oxidative stress and upregulates SIRT1/Nrf2 signaling, preventing the apoptosis of Leydig cells caused by cisplatin.
Article
Biochemistry & Molecular Biology
Romain Gerbier, Delphine Ndiaye-Lobry, Pablo B. Martinez de Morentin, Erika Cecon, Lora K. Heisler, Philippe Delagrange, Florence Gbahou, Ralf Jockers
Summary: Functional fingerprint of heteromers composed of G(i)-coupled melatonin MT2 receptors and G(q)-coupled serotonin 5-HT2C receptors was identified in mouse brain, with melatonin activating G(q) proteins and PLC in a concentration-dependent manner in the hypothalamus and cerebellum. These effects were absent in cortex, inhibited by the 5-HT2C receptor-specific inverse agonist SB-243213, and were fully recapitulated in MT2 and 5-HT2C knockout mice. Furthermore, antidepressant agomelatine had similar effects to melatonin but blocked melatonin-promoted G(q) activation due to its 5-HT2C antagonistic component, providing strong functional evidence for the existence of MT2/5-HT2C heteromeric complexes.
Review
Biochemistry & Molecular Biology
Dmytro Boiko, Anastasiia D. Shkodina, Mohammad Mehedi Hasan, Mainak Bardhan, Syeda Kanza Kazmi, Hitesh Chopra, Prerna Bhutra, Atif Amin Baig, Andrii M. Skrypnikov
Summary: Depressive disorders involve multiple physiological systems and disruption of circadian rhythms. Melatonin, through its action on MT1 and MT2 receptors, may serve as a potential target for novel antidepressants by regulating neurotrophins, neurotransmitters, and reducing inflammation. Targeting melatonergic receptors could improve the quality of therapeutic interventions in treating depression.
NEUROCHEMICAL RESEARCH
(2022)
Article
Clinical Neurology
Francisco Borja Belloch, Elena Beltran, Elisabeth Venzala, Javier Montalt-Tordera, Teresa Diaz-Perdigon, Erika Cecon, Elena Puerta, Philippe Delagrange, Rosa Maria Tordera
Summary: Research on the specific roles of melatonin receptor subtypes MT1 and MT2 in regulating circadian core body temperature and depressive-like behaviors revealed that MT2-/- mice exhibited poorer performance in depression and core body temperature, and increased vulnerability to ultra-mild stress.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Kodchanan Singhanat, Nattayaporn Apaijai, Thidarat Jaiwongkam, Sasiwan Kerdphoo, Siriporn C. Chattipakorn, Nipon Chattipakorn
Summary: This study demonstrates that melatonin administration at different time points during cardiac ischemia/reperfusion injury exerts similar levels of cardioprotection, and its beneficial effects on cardiac arrhythmias and mitochondrial function and dynamics are dependent on the activation of MT2 receptor.
JOURNAL OF ADVANCED RESEARCH
(2021)
Article
Clinical Neurology
David M. Thomson, Emma J. Mitchell, Rebecca L. Openshaw, Judith A. Pratt, Brian J. Morris
Summary: The study found that the MT2 receptor plays a role in the effects of melatonin, as well as modulating anxiety levels and social interactions. These findings provide new insights into the functions of endogenous melatonin and will guide future drug development strategies targeting the MT2 receptor.
JOURNAL OF PSYCHOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Qingyun Guan, Zixu Wang, Keyu Hu, Jing Cao, Yulan Dong, Yaoxing Chen
Summary: Ferroptosis, an iron-dependent cell death, is observed in the development of non-alcoholic fatty liver disease (NAFLD). Melatonin shows potential benefits in preventing and treating liver diseases. In this study, a mouse model of NAFLD induced by long-term high-fat diet feeding was established, and it was found that Melatonin treatment improved metabolic abnormalities and inhibited the progression of NAFLD. Melatonin supplementation also improved iron homeostasis disorders and hepatic lipid peroxidation induced by high-fat diet. Mechanistically, Melatonin inhibited ER stress through the MT2/cAMP/PKA/IRE1 pathway to inhibit hepatic ferroptosis.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Medicine, Research & Experimental
Emine Mulayim, Ibrahim Fatih Karababa, Halit Akbas, Huseyin Bayazit, Salih Selek
Summary: The study revealed that the MTNR1B gene-1193C>T polymorphism may play a role in BD-I genetic etiology and contribute to the sleep disorder and circadian rhythm disorder observed in these patients.
ARCHIVES OF MEDICAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Monika Dmitrzak-Weglarz, Ewa Banach, Karolina Bilska, Beata Narozna, Aleksandra Szczepankiewicz, Edyta Reszka, Ewa Jablonska, Maria Skibinska, Joanna Pawlak
Summary: Melatonin, as a neurohormone, plays a significant role in regulating various systems in the body. This study aimed to comprehensively analyze the differences in melatonin pathway between healthy control subjects and depression patients, identifying specific patterns for unipolar and bipolar depression. Through gene expression profiling in clinical and cell culture models, the study confirmed dysfunctions in molecular regulation of the melatonin biosynthesis pathway in depression, highlighting the immunomodulatory effect of melatonin agents.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Immunology
Ting Gao, Tie Wang, Zixu Wang, Jing Cao, Yulan Dong, Yaoxing Chen
Summary: The study demonstrated that melatonin improved DSS-induced colitis by activating multiple signaling pathways and inhibiting the NF-κB pathway, providing evidence for melatonin as an effective therapy against oxidative stress associated IBD.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Michele Mari, Gian Marco Elisi, Annalida Bedini, Simone Lucarini, Michele Retini, Valeria Lucini, Francesco Scaglione, Fabrizio Vincenzi, Katia Varani, Riccardo Castelli, Marco Mor, Silvia Rivara, Gilberto Spadoni
Summary: The crystal structures of melatonin MT1 and MT2 receptors have revealed the presence of a lipophilic subpocket that accommodates the phenyl ring of the potent agonist 2-phenylmelatonin. This subpocket is crucial for achieving high binding affinity and selectivity for the MT2 receptor. Through a series of experiments and simulations, the optimal occupation and interaction with the 2-phenyl binding pocket have been investigated. The results suggest that more hydrophilic 2-aza-substituted compounds exhibit high binding affinity due to polar interactions with residues from the subpocket.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Psychiatry
Artur Jerzy Ostrzyzek, Piotr Galecki, Slawomir Wolniak, Agata Orzechowska
Summary: Quality of life is an important aspect of a new perspective on health, with both objective and subjective dimensions. Research shows that when examining the quality of life in terms of physical health, it is usually easily achieved; however, when it comes to mental diseases and dysfunctions, the relationship becomes more complex due to the numerous variables involved. Therefore, in addition to methodological accuracy, researchers also need to focus on the patients and their manifestations.
PSYCHIATRIA POLSKA
(2023)
Review
Medicine, General & Internal
Lena Rutkowska, Dominik Salachna, Krzysztof Lewandowski, Andrzej Lewinski, Agnieszka Gach
Summary: Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by a selective loss of adipose tissue, leading to various metabolic complications. The most common types are FPLD type 2 and 3, with variants in LMNA and PPARG genes being frequently observed. Through NGS analysis, a novel c.443G>A variant in the PPARG gene was identified in a symptomatic woman and her family, raising suspicion of its pathogenicity. Understanding the genetic basis of FPLD can facilitate early diagnosis and targeted treatment.
Article
Medicine, General & Internal
Izabela Michalus, Aneta Gawlik, Katarzyna Wieczorek-Szukala, Andrzej Lewinski
Summary: Hypophosphatasia (HPP) is a rare genetic disease that is difficult to diagnose. This study summarizes the clinical manifestations of HPP patients and highlights the diversity and rarity of the symptoms.
Article
Genetics & Heredity
Lena Rutkowska, Iwona Pinkier, Kinga Salacinska, Lukasz Kepczynski, Dominik Salachna, Joanna Lewek, Maciej Banach, Pawel Matusik, Ewa Starostecka, Andrzej Lewinski, Rafal Ploski, Piotr Stawinski, Agnieszka Gach
Summary: The aim of this study was to identify novel CNV changes in FH patients using targeted sequencing and evaluate the suitability of the DECoN tool for CNV calling. The results suggest that the NGS-based approach has the potential to identify large-scale variations in the LDLR gene, but MLPA confirmation is still necessary.
Article
Medicine, General & Internal
Izabela Michalus, Anna Lupinska, Izabela Woch, Katarzyna Wieczorek-Szukala, Danuta Chlebna-Soko, Andrzej Lewinski
Summary: This retrospective study explored the bone turnover and bone mass disorders in children with hypophosphatemic rickets. The results showed that bone metabolism disturbances and worse bone quality were found in these patients. It is crucial to monitor the progress and treatment effects by determining bone turnover markers, dual-energy X-ray absorptiometry findings, and indices of quantitative ultrasound examination.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Medicine, General & Internal
Marzena Kolasa-Kicinska, Renata Stawerska, Pawel Stawerski, Andrzej Kaluzynski, Elzbieta Czkwianianc, Andrzej Lewinski
Summary: This study found that short children infected with H. pylori have lower concentrations of ghrelin and IGF-1 compared to children without infection, which may contribute to their poorer growth rate.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Nutrition & Dietetics
Pawel Pludowski, Beata Kos-Kudla, Mieczyslaw Walczak, Andrzej Fal, Dorota Zozulinska-Ziolkiewicz, Piotr Sieroszewski, Jaroslaw Peregud-Pogorzelski, Ryszard Lauterbach, Tomasz Targowski, Andrzej Lewinski, Robert Spaczynski, Miroslaw Wielgos, Jaroslaw Pinkas, Teresa Jackowska, Ewa Helwich, Artur Mazur, Marek Ruchala, Arkadiusz Zygmunt, Mieczyslaw Szalecki, Artur Bossowski, Justyna Czech-Kowalska, Marek Wojcik, Beata Pyrzak, Michal A. Zmijewski, Pawel Abramowicz, Jerzy Konstantynowicz, Ewa Marcinowska-Suchowierska, Andrius Bleizgys, Spirydon N. Karras, William B. Grant, Carsten Carlberg, Stefan Pilz, Michael F. Holick, Waldemar Misiorowski
Summary: It is found that vitamin D deficiency is prevalent among the Polish population based on epidemiological studies. To address this concern, a Polish multidisciplinary group reviewed the evidence and formulated recommendations for prevention and treatment of vitamin D deficiency. The final Polish recommendations included a range of serum vitamin D levels indicating deficiency, guidelines for prophylaxis and treatment, and the importance of improving the overall population's vitamin D status and treating at-risk patient groups.
Article
Nutrition & Dietetics
Magdalena Basinska-Lewandowska, Krzysztof Lewandowski, Wojciech Horzelski, Andrzej Lewinski, Elzbieta Skowronska-Jozwiak
Summary: The study found a correlation between 25OHD concentrations below 12 ng/mL and an increased risk of COVID-19 infection. However, no significant increase in infection risk was observed for individuals with 25OHD concentrations above 20 ng/mL.
Article
Genetics & Heredity
Magdalena Stasiak, Katarzyna Zawadzka-Starczewska, Boguslaw Tymoniuk, Bartlomiej Stasiak, Andrzej Lewinski
Summary: The risk of GO is higher in patients with elevated TC and/or LDL cholesterol, and this risk is associated with specific HLA alleles. The study investigated the relationship between TC/LDL levels and the presence of GO-related HLA alleles in GD patients. The results showed a correlation between the high-risk HLA alleles (HLA-B*37:01 and C*03:02) and higher TC/LDL levels, as well as lower TC levels in alleles associated with non-GO GD (HLA-C*17:01 and B*08:01).
Review
Medicine, General & Internal
Halliru Zailani, Senthil Kumaran Satyanarayanan, Wei-Chih Liao, Hsien-Feng Liao, Shih-Yi Huang, Piotr Galecki, Kuan-Pin Su, Jane Pei-Chen Chang
Summary: Chronic obstructive pulmonary disease (COPD) is a leading cause of death globally, particularly in individuals over 40 years old. Mood disorders are frequently comorbid with COPD, but often overlooked or undiagnosed, leading to poor treatment outcomes and increased mortality. The exact link between COPD and mood disorders is still uncertain, but it is believed that inflammation in the lungs, blood, and brain may contribute to the development of mood disorders in COPD. Antidepressants are commonly used to manage mood disorders in COPD, but their efficacy is limited due to tolerability issues. Omega-3 polyunsaturated fatty acids (n-3 PUFAs), which regulate inflammatory responses, may offer promising alternatives for managing mood disorders in COPD.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Medicine, General & Internal
Iga Gruszczynska-Sinczak, Katarzyna Wachowska, Katarzyna Blizniewska-Kowalska, Piotr Galecki
Summary: Pregnancy, childbirth, and the postpartum period involve significant physical and psychological changes in a woman's life. This review aims to assess the safety of treatment during pregnancy. The PubMed database was searched, revealing that certain psychiatric medications like valproates are contraindicated during pregnancy, while others like selective serotonin reuptake inhibitors (SSRIs) or antipsychotics are relatively safe. However, treatment decisions should be made cautiously, taking into consideration individual patient characteristics, the severity of the disorder, and the clinical presentation.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Medicine, General & Internal
Anna Lupinska, Sara Aszkielowicz, Grzegorz Zielinski, Renata Stawerska, Andrzej Lewinski
Summary: Cushing's disease is extremely rare in children and this report presents a case of a 16-year-old boy with CD who initially experienced spinal pain and vertebral fractures. After diagnostic tests, CD was confirmed based on cortisol profile results, dexamethasone suppression tests, and bilateral sampling during catheterization of the inferior petrosal sinuses.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Justyna Sobolewska-Nowak, Katarzyna Wachowska, Artur Nowak, Agata Orzechowska, Agata Szulc, Olga Plaza, Piotr Galecki
Summary: Civilization diseases, such as depression and cardiovascular disease, have been increasing and the link between them has been established. This review aims to summarize the risk factors for both diseases and the importance of prevention and treatment of cardiovascular disease in preventing depression. Effective treatment of cardiovascular disease can also improve mental health outcomes.
Article
Biochemistry & Molecular Biology
Piotr Czarny, Sylwia Ziolkowska, Lukasz Kolodziej, Cezary Watala, Paulina Wigner-Jeziorska, Katarzyna Blizniewska-Kowalska, Katarzyna Wachowska, Malgorzata Galecka, Ewelina Synowiec, Piotr Galecki, Michal Bijak, Janusz Szemraj, Tomasz Sliwinski
Summary: This study explores the impact of SNPs in genes encoding enzymes involved in mtDNA replication, repair, or degradation on the occurrence, onset, severity, and treatment of MDD. The findings suggest that mtDNA damage and impairment in its metabolism play a crucial role in the development and treatment of depression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Endocrinology & Metabolism
Malgorzata Karbownik-Lewinska, Jan Stepniak, Paulina Iwan, Andrzej Lewinski
Summary: Excess iodine can interfere with thyroid hormone synthesis and act as a potential endocrine-disrupting chemical through oxidative stress. It is important to be cautious with iodine intake to avoid negative effects on thyroid physiology.
