melatonin

Association of intra-follicular melatonin with reduced oxidative DNA damage and improved oocyte quality in water buffalo: Effect of season and follicular size.

Pandey Anand Kumar AK, Gunwant Pankaj P, Kumar Sandeep S, Saini Gitesh G et al.

Oxidative stress caused by production of reactive oxygen species (ROS) due to normal metabolism and/or external environment results in changes in follicular fluid microenvironment, oxidation of oocyte DNA (8‑hydroxy-2'deoxyguanosine levels; 8-OHdG) and poor-quality oocyte. Therefore, the present investigation was designed to evaluate the relationship between oocyte quality and intra-follicular environment (melatonin, 8-OHdG, 17β-estradiol and progesterone concentrations) in different sized follicles during summer and winter in water buffaloes. Slaughterhouse-derived ovaries were subjected for collection of follicular fluid from three (n = 42 each category in summer and winter) different categories of follicle based on diameter (Small: 8-9.9 mm; Medium: 10-11.9 mm; Large: 12-14 mm). Individual follicles were treated as independent observational units and analyzed using a factorial model including effects of season, follicular size, and their interaction. The results revealed higher (P < 0.05) melatonin and 17β-estradiol concentrations were associated with larger follicles and improved oocyte quality. Melatonin was positively associated (P < 0.05) with 17β-estradiol concentrations in different follicular categories during both seasons. Conversely, 8-OHdG followed an inverse association (P < 0.05) with melatonin in different categories of follicles during both seasons. Irrespective of follicles size, data revealed that good-quality oocytes (Grade A) were associated with higher melatonin concentrations, 102.11±3.88 pg/mL and 116.59±3.32 pg/mL in summer and winter, respectively. Ordinal logistic regression analysis identified melatonin concentration as the only significant independent predictor of oocyte quality (β=-0.226, OR=0.798; P < 0.001). Thus, it may be concluded that higher intra-follicular melatonin concentrations were associated with lower oxidative DNA damage and improved oocyte quality in water buffalo.

Melatonin attenuates ovarian injury concomitantly with alterations in SMAD7 protein expression and related microRNAs in a rat model of adnexal torsion-detorsion.

Ozel Feyyaz F, Sapmaz Tansel T, Kuras Sibel S, Topkaraoglu Sude S et al.

This study aimed to investigate the histopathological and molecular effects of melatonin on ovarian follicle reserve, SMAD7 immunolocalization, and SMAD7-related miRNAs (miR-182, miR-21, miR-92) in a rat model of adnexal torsion-detorsion (TD). Twenty-eight adult female rats were divided into four groups (n = 7). Group 1 (Control) underwent no procedure, while Group 2 (TD) received 2-h torsion followed by 2-h detorsion. Group 3 (TD + Solvent) and Group 4 (TD + Melatonin) were administered ethanol or melatonin intraperitoneally 15 min before detorsion, respectively. Ovarian tissues and serum samples were analyzed histopathologically, biochemically, and molecularly. In Group 2, follicular atrophy, cystic degeneration, and increased connective tissue and vascular congestion were observed, whereas Group 4 exhibited reduced cystic follicles and preserved follicular architecture. SMAD7 expression decreased in Group 2 and increased in Group 4. Although not reaching statistical significance, TOS tended to increase and TAS tended to decrease in Group 2, whereas the opposite trend was observed in Group 4. miR-21, miR-182, and miR-92 expression levels significantly increased in Groups 2 and 3 compared with the control but remained comparable to the control in Group 4. These findings indicate that melatonin contributes to the attenuation of acute structural damage in ovarian follicles, modulation of oxidative stress, and regulation of SMAD7-related miRNAs in the TD model. Melatonin may play a protective role against torsion-detorsion-induced acute ovarian injury, showing a strong association with the modulation of oxidative stress, SMAD7 immunoreactivity, and specific miRNA expression levels.

Expression of concern: "Novel Melatonin, Estrogen, and Progesterone Hormone Therapy Demonstrates Anti-Cancer Actions in MCF-7 and MDA-MB-231 Breast Cancer Cells".

Circadian rhythms and chronotherapy in Alzheimer's disease: Mechanisms and therapeutic implications.

Singh Bivek B, Pigazzani Filippo F, Manfredini Roberto R

Alzheimer's disease (AD), the most prevalent form of dementia, has been increasingly associated with disruptions in circadian rhythms and sleep-wake regulation. This narrative review synthesizes recent literature on how circadian dysfunction may contribute to AD pathogenesis, biomarker profiles, and treatment response. Mechanistic studies suggest important interactions between core clock genes and neurodegenerative cascades involving oxidative stress, neuroinflammation, glial reactivity, and proteostasis. Disruptions in circadian-regulated molecular pathways, including brain and muscle ARNT-like 1 (BMAL1)-sirtuin 1 (SIRT1), nuclear factor kappa B (NF-κB)-NOD-like receptor family pyrin domain containing 3 (NLRP3), and period circadian regulator 2 (PER2)-antioxidant signaling pathways, may compromise neuronal resilience and worsen AD-related pathology. Emerging evidence also suggests distinct circadian patterns in AD-relevant biomarkers, including melatonin, cortisol, orexin, core body temperature, blood-brain barrier permeability, and glial marker oscillations. These rhythmic patterns may have diagnostic and prognostic relevance and support the need for time-aware biomarker interpretation. Chronotherapeutic strategies targeting circadian biology, including melatonin receptor agonists, light therapy, time-restricted feeding, and circadian-aligned drug delivery systems, may help improve targeted clinical endpoints in AD. This review also discusses chronoepigenetics as an emerging area in which clock-regulated epigenetic modifications may influence neurodegenerative trajectories. Future directions include next-generation chronotherapeutic targets, such as glial clocks, clock-gated inflammatory mechanisms, and systemic comorbidities with circadian modulation, including diabetes and hypertension. Overall, the available evidence supports a close association between circadian disruption and both AD pathology and therapeutic response, while also highlighting important gaps in large-scale clinical trials. This time-oriented perspective may support the development of personalized, biomarker-guided, and rhythm-informed approaches to AD care. By bridging chronobiology and neurodegeneration, this review highlights how circadian precision medicine may refine future approaches to understanding and managing AD.