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Melatonin Alleviates Lipopolysaccharide-Induced Abnormal Pregnancy through MTNR1B Regulation of m6A.International Journal of Molecular... Jan 2024Pregnancy is a highly intricate and delicate process, where inflammation during early stages may lead to pregnancy loss or defective implantation. Melatonin, primarily...
Pregnancy is a highly intricate and delicate process, where inflammation during early stages may lead to pregnancy loss or defective implantation. Melatonin, primarily produced by the pineal gland, exerts several pharmacological effects. N6-methyladenosine (m6A) is the most prevalent mRNA modification in eukaryotes. This study aimed to investigate the association between melatonin and m6A during pregnancy and elucidate the underlying protective mechanism of melatonin. Melatonin was found to alleviate lipopolysaccharide (LPS)-induced reductions in the number of implantation sites. Additionally, it mitigated the activation of inflammation, autophagy, and apoptosis pathways, thereby protecting the pregnancy process in mice. The study also revealed that melatonin regulates uterine m6A methylation levels and counteracts abnormal changes in m6A modification of various genes following LPS stimulation. Furthermore, melatonin was shown to regulate m6A methylation through melatonin receptor 1B (MTNR1B) and subsequently modulate inflammation, autophagy, and apoptosis through m6A. In conclusion, our study demonstrates that melatonin protects pregnancy by influencing inflammation, autophagy, and apoptosis pathways in an m6A-dependent manner via MTNR1B. These findings provide valuable insights into the mechanisms underlying melatonin's protective effects during pregnancy and may have implications for potential therapeutic strategies in managing pregnancy-related complications.
Topics: Animals; Female; Mice; Pregnancy; Abortion, Spontaneous; Adenine; Inflammation; Lipopolysaccharides; Melatonin; Receptor, Melatonin, MT2
PubMed: 38255808
DOI: 10.3390/ijms25020733 -
Journal of Neuro-oncology Jan 2024To provide a treatment-focused review and develop basic treatment guidelines for patients diagnosed with pineal anlage tumor (PAT).
PURPOSE
To provide a treatment-focused review and develop basic treatment guidelines for patients diagnosed with pineal anlage tumor (PAT).
METHODS
Prospectively collected data of three patients with pineal anlage tumor from Germany was combined with clinical details and treatment information from 17 published cases.
RESULTS
Overall, 20 cases of PAT were identified (3 not previously reported German cases, 17 cases from published reports). Age at diagnosis ranged from 0.3 to 35.0 (median: 3.2 ± 7.8) years. All but three cases were diagnosed before the age of three years. For three cases, metastatic disease at initial staging was described. All patients underwent tumor surgery (gross-total resection: 9, subtotal resection/biopsy: 9, extent of resection unknown: 2). 15/20 patients were alive at last follow-up. Median follow-up for 10/15 surviving patients with available follow-up and treatment data was 2.4 years (0.3-6.5). Relapse was reported for 3 patients within 0.8 years after diagnosis. Five patients died, 3 after relapse and 2 from early postoperative complications. Two-year-progression-free- and -overall survival were 65.2 ± 12.7% and 49.2 ± 18.2%, respectively. All 4 patients who received intensive chemotherapy including high-dose chemotherapy combined with radiotherapy (2 focal, 2 craniospinal [CSI]) had no recurrence. Focal radiotherapy- and CSI-free survival rates in 13 evaluable patients were 46.2% (6/13) and 61.5% (8/13), respectively.
CONCLUSION
PAT is an aggressive disease mostly affecting young children. Therefore, adjuvant therapy using intensive chemotherapy and considering radiotherapy appears to comprise an appropriate treatment strategy. Reporting further cases is crucial to evaluate distinct treatment strategies.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Infant; Young Adult; Brain Neoplasms; Neoplasm Recurrence, Local; Pineal Gland; Pinealoma; Recurrence; Supratentorial Neoplasms; Treatment Outcome
PubMed: 38253790
DOI: 10.1007/s11060-023-04547-5 -
EMBO Reports Feb 2024Patients with neuropsychiatric disorders often exhibit a combination of clinical symptoms such as autism, epilepsy, or schizophrenia, complicating diagnosis and...
Patients with neuropsychiatric disorders often exhibit a combination of clinical symptoms such as autism, epilepsy, or schizophrenia, complicating diagnosis and development of therapeutic strategies. Functional studies of novel genes associated with co-morbidities can provide clues to understand the pathogenic mechanisms and interventions. NOMO1 is one of the candidate genes located at 16p13.11, a hotspot of neuropsychiatric diseases. Here, we generate nomo1 zebrafish to get further insight into the function of NOMO1. Nomo1 mutants show abnormal brain and neuronal development and activation of apoptosis and inflammation-related pathways in the brain. Adult Nomo1-deficient zebrafish exhibit multiple neuropsychiatric behaviors such as hyperactive locomotor activity, social deficits, and repetitive stereotypic behaviors. The Habenular nucleus and the pineal gland in the telencephalon are affected, and the melatonin level of nomo1 is reduced. Melatonin treatment restores locomotor activity, reduces repetitive stereotypic behaviors, and rescues the noninfectious brain inflammatory responses caused by nomo1 deficiency. These results suggest melatonin supplementation as a potential therapeutic regimen for neuropsychiatric disorders caused by NOMO1 deficiency.
Topics: Animals; Adult; Humans; Zebrafish; Melatonin; Autistic Disorder; Brain
PubMed: 38253686
DOI: 10.1038/s44319-023-00036-y -
Annals of Medicine and Surgery (2012) Jan 2024
PubMed: 38222765
DOI: 10.1097/MS9.0000000000001542 -
Journal of Translational Medicine Jan 2024Chimeric antigen receptor CAR-T cell therapies have ushered in a new era of treatment for specific blood cancers, offering unparalleled efficacy in cases of treatment...
BACKGROUND
Chimeric antigen receptor CAR-T cell therapies have ushered in a new era of treatment for specific blood cancers, offering unparalleled efficacy in cases of treatment resistance or relapse. However, the emergence of cytokine release syndrome (CRS) as a side effect poses a challenge to the widespread application of CAR-T cell therapies. Melatonin, a natural hormone produced by the pineal gland known for its antioxidant and anti-inflammatory properties, has been explored for its potential immunomodulatory effects. Despite this, its specific role in mitigating CAR-T cell-induced CRS remains poorly understood.
METHODS
In this study, our aim was to investigate the potential of melatonin as an immunomodulatory agent in the context of CD19-targeting CAR-T cell therapy and its impact on associated side effects. Using a mouse model, we evaluated the effects of melatonin on CAR-T cell-induced CRS and overall survival. Additionally, we assessed whether melatonin administration had any detrimental effects on the antitumor efficacy and persistence of CD19 CAR-T cells.
RESULTS
Our findings demonstrate that melatonin effectively mitigated the severity of CAR-T cell-induced CRS in the mouse model, leading to improved overall survival outcomes. Remarkably, melatonin administration did not compromise the antitumor effectiveness or persistence of CD19 CAR-T cells, indicating its compatibility with therapeutic goals. These results suggest melatonin's potential as an immunomodulatory compound to alleviate CRS without compromising the therapeutic benefits of CAR-T cell therapy.
CONCLUSION
The study's outcomes shed light on melatonin's promise as a valuable addition to the existing treatment protocols for CAR-T cell therapies. By attenuating CAR-T cell-induced CRS while preserving the therapeutic impact of CAR-T cells, melatonin offers a potential strategy for optimizing and refining the safety and efficacy profile of CAR-T cell therapy. This research contributes to the evolving understanding of how to harness immunomodulatory agents to enhance the clinical application of innovative cancer treatments.
Topics: Antigens, CD19; Cell- and Tissue-Based Therapy; Cytokine Release Syndrome; Immunologic Factors; Immunotherapy, Adoptive; Melatonin; Neoplasm Recurrence, Local; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; Animals; Mice
PubMed: 38221609
DOI: 10.1186/s12967-023-04779-z -
International Journal of Surgery... Mar 2024
Topics: Humans; Retrospective Studies; Pinealoma; Brain Neoplasms; Pineal Gland; Neurosurgical Procedures
PubMed: 38215266
DOI: 10.1097/JS9.0000000000001038 -
Cureus Dec 2023Pineal parenchymal tumors of intermediate differentiation (PPTIDs) account for a significant proportion of pineal tumors and are classified as grade II/III according to...
Pineal parenchymal tumors of intermediate differentiation (PPTIDs) account for a significant proportion of pineal tumors and are classified as grade II/III according to the WHO classification. The management of PPTIDs remains controversial because of limited reported cases and the absence of standardized treatment guidelines. We present a case of an eight-year-old male child who presented with vomiting and a sudden squint of the eyes. Imaging revealed a well-defined heterogeneous enhancing lesion in the pineal region with acute hydrocephalus. The patient underwent surgical resection, and the tumor was diagnosed as PPTID. Local recurrence occurred 10 months later, requiring a second surgical intervention and adjuvant radiation therapy. A follow-up showed a regression of the tumor and improvement in symptoms. A literature review of reported PPTID cases revealed variability in clinical presentation, treatment approaches, and outcomes. Headaches were the most common symptom, and surgical resection was the primary treatment modality. Adjuvant therapies such as radiation therapy and chemotherapy were utilized in some cases. Tumor recurrence was observed in several instances, underscoring the need for long-term follow-up. In conclusion, PPTIDs are rare brain tumors with challenging diagnosis and management. Surgical resection remains the mainstay of treatment; however, the optimal approach is uncertain. Standardized reporting and larger studies are necessary to establish guidelines for the management of PPTIDs and improve long-term outcomes.
PubMed: 38192964
DOI: 10.7759/cureus.50139 -
Oncology Research 2023Melatonin is a versatile indolamine synthesized and secreted by the pineal gland in response to the photoperiodic information received by the retinohypothalamic...
Melatonin is a versatile indolamine synthesized and secreted by the pineal gland in response to the photoperiodic information received by the retinohypothalamic signaling pathway. Melatonin has many benefits, such as organizing circadian rhythms and acting as a powerful hormone. We aimed to show the antitumor effects of melatonin in both and models through the mammalian target of rapamycin (mTOR) signaling pathway and the Argyrophilic Nucleolar Regulatory Region (AgNOR), using the Microcomputed Tomography (Micro CT). Ehrlich ascites carcinoma (EAC) cells were administered into the mice by subcutaneous injection. Animals with solid tumors were injected intraperitoneally with 50 and 100 mg/kg melatonin for 14 days. Volumetric measurements for the taken tumors were made with micro-CT imaging, immunohistochemistry (IHC), real-time polymerase chain reaction (PCR) and AgNOR. Statistically, the tumor tissue volume in the Tumor+100 mg/kg melatonin group was significantly lower than that in the other groups in the data obtained from micro-CT images. In the IHC analysis, the groups treated with Tumor+100 mg/kg melatonin were compared when the mTOR signaling pathway and factor 8 (F8) expression were compared with the control group. It was determined that there was a significant decrease ( < 0.05). Significant differences were found in the total AgNOR area/nuclear area (TAA/NA) ratio in the treatment groups ( < 0.05). Furthermore, there were significant differences between the amount of mTOR mRNA for the phosphatidylinositol 3-kinase (PI3K), AKT Serine/Threonine Kinase (PKB/AKT) genes ( < 0.05). Cell apoptosis was evaluated with Annexin V in an study with different doses of melatonin; It was observed that 100 µg/mL melatonin dose caused an increase in the apoptotic cell death. In this study, we have reported anti-tumor effects of melatonin in cell culture studies as well as in mice models. Comprehensive characterization of the melatonin-mediated cancer inhibitory effects will be valuable in advancing our fundamental molecular understanding and translatability of pre-clinical findings to earlier phases of clinical trials.
Topics: Humans; Animals; Mice; Melatonin; X-Ray Microtomography; Ascites; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Carcinoma; TOR Serine-Threonine Kinases; Mammals
PubMed: 38188676
DOI: 10.32604/or.2023.042350 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Dec 2023Melatonin,an endocrine hormone synthesized by the pineal gland,plays an important role in the reproduction.The growth and development of follicles is the basis of female... (Review)
Review
Melatonin,an endocrine hormone synthesized by the pineal gland,plays an important role in the reproduction.The growth and development of follicles is the basis of female mammalian fertility.Follicles have a high concentration of melatonin.Melatonin receptors exist on ovarian granulosa cells,follicle cells,and oocytes.It regulates the growth and development of these cells and the maturation and atresia of follicles,affecting female fertility.This paper reviews the protective effects and regulatory mechanisms of melatonin on the development of ovarian follicles,granulosa cells,and oocytes and makes an outlook on the therapeutic potential of melatonin for ovarian injury,underpinning the clinical application of melatonin in the future.
Topics: Animals; Female; Melatonin; Ovarian Follicle; Oocytes; Granulosa Cells; Mammals
PubMed: 38173113
DOI: 10.3881/j.issn.1000-503X.15473 -
Hormone and Metabolic Research =... Jun 2024Melatonin (5-methoxy-acetyl tryptamine) is a sleep-inducing hormone, and the pineal gland produces it in response to the circadian clock of darkness. In the body, MT1... (Review)
Review
Melatonin (5-methoxy-acetyl tryptamine) is a sleep-inducing hormone, and the pineal gland produces it in response to the circadian clock of darkness. In the body, MT1 and MT2 receptors are mostly found, having an orthosteric pocket and ligand binding determinants. Melatonin acts by binding on melatonin receptors, intracellular proteins, and orphan nuclear receptors. It inhibits adenyl cyclase and activates phospholipase C, resulting in gene expression and an intracellular alteration environment. Melatonin signaling pathways are also associated with other intracellular signaling pathways, i. e., cAMP/PKA and MAPK/ERK pathways. Relative expression of different proteins depends on the coupling profile of G protein, accounting pharmacology of the melatonin receptor bias system, and mediates action in a Gi-dependent manner. It shows antioxidant, antitumor, antiproliferative, and neuroprotective activity. Different types of melatonin agonists have been synthesized for the treatment of sleeping disorders. Researchers have developed therapeutics that target melatonin signaling, which could benefit a wide range of medical conditions. This review focuses on melatonin receptors, pharmacology, and signaling cascades; it aims to provide basic mechanical aspects of the receptor's pharmacology, melatonin's functions in cancer and neurodegenerative diseases, and any treatments and drugs designed for these diseases. This will allow a basic comparison between the receptors in question, highlighting any parallels and differences that may exist and providing fundamental knowledge about these receptors to future researchers.
Topics: Humans; Melatonin; Signal Transduction; Animals; Receptors, Melatonin; Neoplasms; Neurodegenerative Diseases
PubMed: 38081221
DOI: 10.1055/a-2226-3971