Placental Infections.

This comprehensive review examines the effects of various infections on pregnancy, focusing on maternal symptoms, fetal outcomes, diagnostic methods, and placental pathology. The paper covers bacterial, viral, and parasitic infections, their mechanisms of transmission, clinical presentations, and histopathologic findings in the placenta. It emphasizes the importance of early detection and intervention, highlighting the challenges in diagnosis due to often asymptomatic presentations.

Co-administering Melatonin With an Estradiol-Progesterone Menopausal Hormone Therapy Represses Mammary Cancer Development in a Mouse Model of HER2-Positive Breast Cancer.

Melatonin has numerous anti-cancer properties reported to influence cancer initiation, promotion, and metastasis. With the need for effective hormone therapies (HT) to treat menopausal symptoms without increasing breast cancer risk, co-administration of nocturnal melatonin with a natural, low-dose HT was evaluated in mice that develop primary and metastatic mammary cancer. Individually, melatonin (MEL) and estradiol-progesterone therapy (EPT) did not significantly affect mammary cancer development through age 14 months, but, when combined, the melatonin-estradiol-progesterone therapy (MEPT) significantly repressed tumor formation.

Effects on bone by the light/dark cycle and chronic treatment with melatonin and/or hormone replacement therapy in intact female mice.

In this study, the effects of the light/dark cycle, hormone replacement therapy (HRT), and nocturnal melatonin supplementation on osteogenic markers and serum melatonin levels were examined in a blind mouse model (MMTV-Neu transgenic mice). Melatonin levels in this mouse strain (FVB/N) with retinal degeneration (rd-/-) fluctuate in a diurnal manner, suggesting that these mice, although blind, still perceive light. Real-time RT-PCR analyses demonstrated that Runx2, Bmp2, Bmp6, Bglap, and Per2 mRNA levels coincide with melatonin levels.

N-Acetyl-5-arylalkoxytryptamine analogs: probing the melatonin receptors for MT(1) -selectivity.

A series of melatonin analogs obtained by the replacement of the ether methyl group with larger arylalkyl and aryloxyalkyl substituents was prepared in order to probe the melatonin receptors for MT(1) -selectivity. The most MT(1) -selective agents 11 and 15 were substituted with a Ph(CH(2) )(3) or a PhO(CH(2) )(3) group. Compounds 11 and 15 displayed 11.

Determination of the minimal melatonin exposure required to induce osteoblast differentiation from human mesenchymal stem cells and these effects on downstream signaling pathways.

The purpose of this study was to determine the critical time periods of melatonin treatment required to induce human mesenchymal stem cells (hAMSCs) into osteoblasts and to determine which osteogenic genes are involved in the process. The study design consisted of adding melatonin for different times (2, 5, 10, 14 or 21 days) toward the end of a 21-day treatment containing osteogenic (OS+) medium or at the beginning of the 21-day treatment and then withdrawn. The results show that a 21-day continuous melatonin treatment was required to induce both alkaline phosphatase (ALP) activity and calcium deposition and these effects were mediated through MT₂Rs.

Synthesis and pharmacological evaluation of 1,2,3,4-tetrahydropyrazino[1,2-a]indole and 2-[(phenylmethylamino)methyl]-1H-indole analogues as novel melatoninergic ligands.

Two novel series of melatonin-derived compounds have been synthesized and pharmacologically evaluated at the MT(1) and MT(2) subtypes of melatonin receptors. Compounds 12b-c are non-selective high-affinity MT(1) and MT(2) receptor ligands (K(i)=7-11 nM). Compound 12b had little intrinsic activity at the MT(1) receptor and no intrinsic activity at the MT(2) receptor.

2-[(2,3-dihydro-1H-indol-1-yl)methyl]melatonin analogues: a novel class of MT2-selective melatonin receptor antagonists.

A novel series of 2-[(2,3-dihydro-1H-indol-1-yl)methyl]melatonin analogues has been prepared to probe the steric and electronic properties of the binding pocket of the MT(2) receptor accommodating the "out-of-plane" substituent of MT(2)-selective antagonists. The acetamide (6b) bearing an usubstituted indoline moiety displayed an excellent binding affinity and selectivity toward the MT(2)-subtype (MT(2), K(i) = 1 nM; MT(1), K(i) = 115 nM), behaving as a competitive antagonist. 5-Me, 5-OMe, 5-Br, 6-NH(2), and 6-NO(2) substitution of the indoline moiety reduced both MT(2) affinity and selectivity, indicating that hydrophobic interactions play a decisive role in binding the out-of-plane substituent.

C-terminal domains within human MT1 and MT2 melatonin receptors are involved in internalization processes.

Melatonin, a molecule implicated in a variety of diseases, including cancer, often exerts its effects through G-protein-coupled melatonin receptors, MT(1) and MT(2). In this study, we sought to understand further the domains involved in the function and desensitization patterns of these receptors through site-directed mutagenesis. Two mutations were constructed in the cytoplasmic C-terminal tail of each receptor subtype: (i) a cysteine residue in the C-terminal tail was mutated to alanine, thus removing a putative palmitoylation site, and a site possibly required for normal receptor function (MT(1)C7.