Still too little evidence: the role of diet in colorectal cancer survivorship - a systematic review.

Colorectal cancer incidence (CRC) is influenced by dietary factors, yet the impact of diet on CRC-specific mortality and recurrence-free survival (RFS) remains unclear. This review provides a narrative summary of existing research on dietary factors affecting CRC-specific mortality, RFS, and disease-free survival (DFS). This study searched electronic databases to identify cross-sectional/prospective research investigating dietary intake on CRC-specific mortality, RFS, or DFS. Twenty-eight studies were included in the corpus. Because of high study heterogeneity, we performed a narrative synthesis of studies. Limited, but suggestive evidence indicates beneficial effects of adhering to the American Cancer Society (ACS) guidelines and a plant rich low-carbohydrate diet on risk of CRC-specific mortality, potentially driven by fiber from cereals, vegetables, and wholegrains, but not fruit. For RFS and DFS, a Western dietary pattern, high intake of refined grains, and sugar sweetened beverages correlated with increased risk of CRC recurrence and development of disease/death. Conversely, greater adherence to the ACS dietary and alcohol guidelines, higher ω-3 polyunsaturated fatty acids, and dark fish consumption reduced risk. Our findings underscore the need for (i) standardized investigations into diet's role in CRC survivorship, including endpoints, and (ii) comprehensive analyses to isolate specific effects within correlated lifestyle components.

Melatonin/Cyclodextrin Inclusion Complexes: A Review.

Melatonin (MLT) is involved in many functions of the human body, mainly in sleeping-related disorders. It also has anti-oxidant potential and has been proven very effective in the treatment of seasonal affective disorders (SAD), which afflict some people during short winter days. Melatonin has been implicated in a range of other conditions, including Parkinson's disease, Alzheimer's and other neurological conditions, and in certain cancers. Its poor solubility in water leads to an insufficient absorption that led scientists to investigate MLT inclusion in cyclodextrins (CDs), as inclusion of drugs in CDs is a way of increasing the solubility of many lipophilic moieties with poor water solubility. The aim of this review is to gather all the key findings on MLT/CD complexes. The literature appraisal concluded that MLT inclusion leads to a 1:1 complex with the majority of CDs and increases the solubility of the hormone. The interactions of MLT with CDs can be studied by a variety of techniques, such as NMR, FT-IR, XRD and DCS. More importantly, the in vivo experiments showed an increase in the uptake of MLT when included in a CD.

3D-Printed Melatonin Tablets with Braille Motifs for the Visually Impaired.

An innovative approach for creating customized dosage forms and supporting patient populations with specific requirements who need additional support to improve drug adherence is 3D printing. This work introduces liquid crystal display (LCD) 3D printing as a means of developing melatonin (MLT) tablets. For patients who are blind or visually challenged, Braille patterns were displayed on the tablet surface in addition to the optimization of printing hydrogel inks. Owing to the great printing accuracy, blind patients could validate the Braille patterns that provided the required information. Upon further examination MLT was found to be present in the photopolymerized resins in an amorphous state. The choice of poly(ethylene glycol)-diacrylate (PEGDA) with varying molecular weights and the inclusion of surfactants or solubilizers interfered with the photopolymerization of the resin, hence controlling the rates of MLT dissolution towards the sought sustained release. Nuclear magnetic resonance (NMR) analysis showed that photopolymerization of the PEGDA resins in the printed dosage forms has taken place. A small batch scale-up investigation showed that LCDs could print a significant number of tablets quickly-about twenty-four minutes.

Potent Lipophilic Melatoninergic x-fluoro-y-methoxy Substituted Phenylalkylamides: Molecular Dynamics Calculations and in vitro Modified Release in Aqueous Media from Tablet Formulations.

INTRODUCTION: We report herein on the design and development of matrix tablets containing potent synthetic melatonin (MLT) receptor analogues, the x-fluoro-y-methoxy substitiuted phenylalkylamides (compounds I-IV), the preparation and melatoninergic potency of which was recently communicated. > Methods: The presence of the fluorine atom in compounds I-IV, besides not affecting their binding affinity, compared to the pineal hormone melatonin, it also slows down their metabolism, which is a major drawback of MLT. However, as fluorine increases the lipophilicity, solid pharmaceutical formulations of I-IV, involving the appropriate biopolymers for their modified release in aqueous media, were developed in the context of the present work. > Results: The release profile of analogues I-IV was found to be similar to that of MLT and also of the commercially available drug, Circadin®. Some of these systems are suitable for dealing with sleep onset problems, whilst others for dealing with combined sleep onset/sleep maintenance problems. > Conclusion: Apart from the nature and relevant content of the formulants used, this bimodal release profile of the new analogues depends, to a large extent, on the diverse structural arrangement of their side chains in space, as nicely demonstrated by the molecular dynamics calculations, conducted in the context of this study. >.

Mapping the Melatonin Receptor. 8. Selective MT2 Agonists Derived from 5,6-Dihydroindolo[2,1-a]isoquinolines and Related Systems.

A series of substituted indolo[2,1-a]isoquinolines and indolo[1,2-a]benzoxazines have been prepared, as melatonin analogues, to investigate the nature of the binding site of the melatonin receptor. Agonist and antagonist potency of all the analogues was measured using the [35S]GTPγS binding assay protocol. The binding affinity of the analogues were measured by competition binding studies against the human MT1 (hMT1) and MT2 (hMT2) receptors stably transfected in Chinese Hamster Ovarian (CHO) cells, using 2-[125 I]-iodomelatonin, as a ligand. N-Acetyl 2-(10-methoxy-5,6-dihydroindolo[2,1-a]isoquinolin-12-yl)propyl-1-amine (12 a) binds strongly to both the hMT1 and hMT2 receptors, and shows a preference for the hMT2, as does its propanamido counterpart 12 b. The introduction of two methyl groups into their side chain, analogues 15 a and 15 b, leads to antagonism, in the case of the former, and drastically diminishes its hMT1 binding; an analogous profile is seen for 15 b, which, however, is a partial agonist. Introduction of chlorine or methoxy groups into ring 4 gives compounds, that are weakly binding, with a preference for MT2. Substitution of oxygen for carbon at position 5 gives the indolo[1,2-c]benzoxazines 33, 36 a and b, that bind strongly to the human receptors, 33, 36 b being potent agonists at the melatonin receptors, but do not discriminate between hMT1 and hMT2.