Obesity and colorectal cancer (CRC) are among the leading diseases causing deaths in the world, showing a complex multifactorial pathology. Obesity is considered a risk factor in CRC development through inflammation, metabolic, and signaling processes. Leptin is one of the most important adipokines related to obesity and an important proinflammatory marker, mainly expressed in adipose tissue, with many genetic variation profiles, many related influencing factors, and various functions that have been ascribed but not yet fully understood and elucidated, the most important ones being related to energy metabolism, as well as endocrine and immune systems. Aberrant signaling and genetic variations of leptin are correlated with obesity and CRC, with the genetic causality showing both inherited and acquired events, in addition to lifestyle and environmental risk factors; these might also be related to specific pathogenic pathways at different time points. Moreover, mutation gain is a crucial factor enabling the genetic process of CRC. Currently, the inconsistent and insufficient data related to leptin’s relationship with obesity and CRC indicate the necessity of further related studies. This review summarizes the current knowledge on leptin genetics and its potential relationship with the main pathogenic pathways of obesity and CRC, in an attempt to understand the molecular mechanisms of these associations, in the context of inconsistent and contradictory data. The understanding of these mechanisms linking obesity and CRC could help to develop novel therapeutic targets and prevention strategies, resulting in a better prognosis and management of these diseases.
Background Many food items included in the Mediterranean diet (MedDiet) are rich in polyamines, small aliphatic amines with potential cardioprotective effects. The consumption of a MedDiet could increase polyamine concentrations. Based on experimental models, polyamine concentrations may be also influenced by physical activity (PA). Objectives We aimed to evaluate whether an intervention based on an energy-restricted MedDiet (er-MedDiet) and PA promotion, in comparison with an energy-unrestricted MedDiet and traditional health care, influences the serum pattern of polyamines and related metabolites in subjects at high risk of cardiovascular disease (CVD). Methods This was a substudy from the PREDIMED-Plus trial, an ongoing randomized clinical trial including 6874 participants allocated either to an intensive weight-loss lifestyle intervention based on er-MedDiet, PA promotion, and behavioral support (er-MedDiet + PA group), or to an energy-unrestricted MedDiet and traditional health care group (MedDiet group). A total of 75 patients (n = 38, er-MedDiet + PA group; n = 37, MedDiet group) were included in this study. Serum concentrations of arginine, ornithine, polyamines, and acetyl polyamines at baseline and 26 wk of intervention were measured by an ultra-high-performance LC–tandem MS platform. Results At week 26, study groups had similar adherence to the MedDiet but patients randomly assigned to the er-MedDiet + PA group showed significantly lower mean energy intake (−340.3 kcal/d; 95% CI: −567.3, −113.4 kcal/d; P = 0.004), higher mean PA (1290.6; 95% CI: 39.9, 2541.3 metabolic equivalent tasks · min/d; P = 0.043), and higher mean decrease in BMI (in kg/m2) (−1.3; 95% CI: −1.8, −0.6; P < 0.001) than the MedDiet group. However, no significant differences in serum polyamines or related metabolites were found between study groups after 26 wk of intervention and no significant between-group differences were found in glycated hemoglobin, HDL-cholesterol, or triglyceride concentrations. Conclusions In individuals at high CVD risk, an er-MedDiet with increased PA did not result in significant changes of serum concentrations of polyamines or related metabolites in comparison with an energy-unrestricted MedDiet and no increase in PA. This trial was registered at isrctn.com as ISRCTN89898870.
Silk fibroin nanoparticles (SFN) have become a promising tool in drug delivery systems due to their physicochemical characteristics. SFN have shown their outstanding properties as an active vehicle for polyphenols, enhancing their antioxidant and anti-inflammatory effects on macrophages; therefore, it becomes necessary to have an easy, reproducible and scalable production method. In order to improve the production of nanoparticles, we performed direct precipitation of non-dialyzed silk fibroin solutions and evaluated the reproducibility of the method using dynamic light scattering. We also studied the loading efficiency of three different natural polyphenols using propylene glycol as a solvent. The loaded nanoparticles were fully characterized and used to treat human macrophage cells to assess the anti-inflammatory activity of these nanoparticles. The measured hydrodynamic characteristics of the SFN and the overall yield of the process showed that the new preparation method is highly reproducible and repeatable. Thus, we not only present a new scalable method to prepare silk nanoparticles but also how to improve the loading of natural polyphenolic compounds to the SFN, as well as the important anti-inflammatory effects of these loaded nanoparticles in a cell model of human macrophage cells.
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