Exercise, Diet and Sleeping as Regenerative Medicine Adjuvants: Obesity and Ageing as Illustrations

Regenerative medicine uses the biological and medical knowledge on how the cells and tissue regenerate and evolve in order to develop novel therapies. Health conditions such as ageing, obesity and cancer lead to an impaired regeneration ability. Exercise, diet choices and sleeping pattern have significant impacts on regeneration biology via diverse pathways including reducing the inflammatory and oxidative components. Thus, exercise, diet and sleeping management can be optimized towards therapeutic applications in regenerative medicine. It could allow to prevent degeneration, optimize the biological regeneration and also provide adjuvants for regenerative medicine.

A single nucleotide polymorphism in BCAT1 gene is associated with type 2 diabetes mellitus

The level of circulatory branched chain amino acids (BCAAs) is often increased in type 2 diabetes mellitus (T2DM). Catabolism of BCAAs involves a transamination reaction mediated by the branched chain amino acid aminotransferase (BCAT1) enzyme. Differences in the level of BCAT1 were found to be linked with hypertension, obesity, and cancer. Herein, using a case control design, we tested the association of rs9668920 and rs12321766 polymorphisms in BCAT1 gene with T2DM. Three hundred subjects were recruited in the study. Genotyping of the indicated polymorphisms was achieved using restriction fragment length polymorphism technique after amplification of the target sequences. The results showed that, under a recessive inheritance model, the GG genotype of rs9668920 increased the risk of T2DM (P=0.026; OR 2.60; 95% CI 1.119–6.048). This effect was independent of the age, body mass index, waist circumference, serum glucose, cholesterol, triglycerides, and BCAAs (P>0.05). In conclusion, The GG genotype of BCAT1 rs9668920 SNP might be a risk factor of T2DM. More studies are required to confirm this finding.

The Deleterious Effects of Impaired Fibrinolysis on Skeletal Development Are Dependent on Fibrin(ogen), but Independent of Interlukin-6

Chronic diseases in growing children, such as autoimmune disorders, obesity, and cancer, are hallmarked by musculoskeletal growth disturbances and osteoporosis. Many of the skeletal changes in these children are thought to be secondary to chronic inflammation. Recent studies have likewise suggested that changes in coagulation and fibrinolysis may contribute to musculoskeletal growth disturbances. In prior work, we demonstrated that mice deficient in plasminogen, the principal protease of degrading and clearing fibrin matrices, suffer from inflammation-driven systemic osteoporosis and that elimination of fibrinogen resulted in normalization of IL-6 levels and complete rescue of the skeletal phenotype. Given the intimate link between coagulation, fibrinolysis, and inflammation, here we determined if persistent fibrin deposition, elevated IL-6, or both contribute to early skeletal aging and physeal disruption in chronic inflammatory conditions. Skeletal growth as well as bone quality, physeal development, and vascularity were analyzed in C57BL6/J mice with plasminogen deficiency with and without deficiencies of either fibrinogen or IL-6. Elimination of fibrinogen, but not IL-6, rescued the skeletal phenotype and growth disturbances in this model of chronic disease. Furthermore, the skeletal phenotypes directly correlated with both systemic and local vascular changes in the skeletal environment. In conclusion, these results suggest that fibrinolysis through plasmin is essential for skeletal growth and maintenance, and is multifactorial by limiting inflammation and preserving vasculature.

What to feed or what not to feed-that is still the question

Introduction This review addresses metabolic diversities after grain feeding of cattle using artificial total mixed ration (TMR), in place of pasture-based feeding. Objectives To determine how grain feeding impairs the deuterium-depleting functions of the anaplerotic mitochondrial matrix during milk and meat production. Methods Based on published data we herein evaluate how grain-fed animals essentially follow a branched-chain amino acid and odd-chain fatty acid-based reductive carboxylation-dependent feedstock, which is also one of the mitochondrial deuterium-accumulating dysfunctions in human cancer. Results It is now evident that food-based intracellular deuterium exchange reactions, especially that of glycogenic substrate oxidation, are significant sources of deuterium-enriched (2H; D) metabolic water with a significant impact on animal and human health. The burning of high deuterium nutritional dairy products into metabolic water upon oxidation in the human body may contribute to similar metabolic conditions and diseases as described in state-of-the-art articles for cows. Grain feeding also limits oxygen delivery to mitochondria for efficient deuterium-depleted metabolic water production by glyphosate herbicide exposure used in genetically modified crops of TMR constituents. Conclusion Developments in medical metabolomics, biochemistry and deutenomics, which is the science of biological deuterium fractionation and discrimination warrant urgent critical reviews in order to control the epidemiological scale of population diseases such as diabetes, obesity and cancer by a thorough understanding of how the compromised metabolic health of grain-fed dairy cows impacts human consumers.

OBESITY AND ITS RELATIONSHIP WITH CANCER: PART I OBESITY

Cancer is a lethal disease and a strong barrier to a better life expectancy. It is the first or second leading cause of death before the age of 70 years in 112 of 183 countries. Its incidence and mortality continue to grow rapidly all over the world. This manuscript is divided into four parts. Part I discusses obesity while Part II discusses the relationship between obesity and cancer. Part III and Part IV review the association of obesity on fifteen common cancers.

OBESITY AND ITS RELATIONSHIP WITH CANCER: PART III

Obesity and cancer has been discussed in the first two parts. This part (Part III) deals with six cancers, namely those involving the breast, colorectal tissues, esophagus, stomach. gall bladder, and liver. Their relationship with obesity is discussed. Part IV will look at endometrial, ovarian, pancreatic, prostate, renal, thyroid and lung carcinomas. Meningioma and multiple myeloma are also discussed.

Obesity and Roux-en-Y gastric bypass drive changes in miR-31 and miR-215 expression in the human rectal mucosa

Background/Objectives Obesity increases colorectal cancer (CRC) risk. However, the effects of weight loss on CRC risk are unclear. Epigenetic mechanisms involving microRNAs that lead to dysregulated gene expression may mediate the effects of obesity and weight loss on CRC risk. We examined the effects of obesity and weight loss following Roux-en-Y gastric bypass (RYGB) on microRNA expression in the human rectal mucosa. Subjects/Methods We collected rectal mucosal biopsies from obese patients (n = 22) listed for RYGB and age- and sex-matched healthy non-obese Controls (n = 20), at baseline and six months post-surgery. We quantified microRNA expression in rectal mucosal biopsies using Next Generation Sequencing and bioinformatics analysis to investigate the likely functional consequences of these epigenetic changes. Results Compared with non-obese individuals, obese individuals showed differential expression of 112 microRNAs (p < 0.05). At six-months post-RYGB, when mean body mass had fallen by 27 kg, 60 microRNAs were differentially expressed, compared with baseline (p < 0.05). The expression of 36 microRNAs differed significantly between both i) obese and non-obese individuals and ii) obese individuals pre- and post-RYGB. Quantitative polymerase chain reaction (qPCR) demonstrated that expression of miR-31 and miR-215 was significantly (p < 0.05) higher, 143-fold and 15-fold respectively, in obese than in non-obese individuals. Weight loss, following RYGB, reduced expression of miR-31 and miR-215 to levels comparable with Controls. These differentially expressed microRNAs are implicated in pathways linked with inflammation, obesity and cancer. Conclusion Our findings show, for the first time, that obesity is associated with dysregulated microRNA expression in the human rectal mucosa. Further, surgically-induced weight loss may normalise microRNA expression in this tissue.

Macrophages as Emerging Key Players in Mitochondrial Transfers

Macrophages are a group of heterogeneous cells widely present throughout the body. Under the influence of their specific environments, via both contact and noncontact signals, macrophages integrate into host tissues and contribute to their development and the functions of their constituent cells. Mitochondria are essential organelles that perform intercellular transfers to regulate cell homeostasis. Our review focuses on newly discovered roles of mitochondrial transfers between macrophages and surrounding cells and summarizes emerging functions of macrophages in transmitophagy, metabolic regulation, and immune defense. We also discuss the negative influence of mitochondrial transfers on macrophages, as well as current therapies targeting mitochondria in macrophages. Regulation of macrophages through mitochondrial transfers between macrophages and their surrounding cells is a promising therapy for various diseases, including cardiovascular diseases, inflammatory diseases, obesity, and cancer.