Artificial Sweeteners And Type 2 Diabetes Study

Here is an article on artificial sweeteners and type 2 diabetes risk.  Abstract:

BACKGROUND:

The influence of artificial sweeteners on metabolic diseases is controversial. Artificially sweetened beverages have been associated with an increased risk of type 2 diabetes (T2D) but biases and reverse causation have been suspected to have influenced the observed association. In addition, it has been suggested that investigation into the relationship between the frequency and duration of the consumption of packet or tablet artificial sweeteners and T2D risk is necessary.

METHODS:

We used data from 61,440 women in the prospective E3N-European Prospective Investigation into Cancer and Nutrition study, conducted between 1993 and 2011. We estimated hazards ratios (HRs) and 95% CIs of T2D risk associated with both the frequency and the duration of use of artificial sweeteners consumed in packets or tablets.

RESULTS:

Compared to "never or rare" consumers of artificial sweeteners, those using them "always or almost always" had an increased risk of T2D (HR = 1.83 [95% CI 1.66-2.02] in the multivariate model [MM], HR = 1.33 [95% CI 1.20-1.47] when further adjusted for body mass index, BMI). Women consuming artificial sweeteners in packets or tablets for more than 10 years also had an increased risk of T2D compared to never or rare users (HR = 2.10 [95% CI 1.83-2.40] in the MM and HR = 1.15 [95% CI 1.00-1.33] when adjusted for BMI, respectively).

CONCLUSIONS:

Our data suggest that both a higher frequency and a longer consumption of artificial sweeteners in packets or tablets was associated with T2D risk, independently of major T2D risk factors, but partially mediated by adiposity. A precautionary principle should be applied to the promotion of these products that are still largely recommended as healthy sugar substitutes.

A reasonable strategy may be to not use such artificial sweeteners and cut down on sugar in your diet as well. Avoid diabetes, and your health will thank you for it.

Dangers Of Shift And Night Work

Here is an article outlining the dangers of shift/nigh work to human health.

Shift/night work disrupts normal circadian (internal timing) rhythms, affecting sleep and promoting disorders “including cancer, diabetes, cardiovascular risks, obesity, mood disorders and age-related macular degeneration. “  Melatonin secretion may be involved.  The paper suggests “melatonin, bright light, or psychotropic drugs, have been proposed as a means to combat circadian clock disruption and improve adaptation to shift and night work.”

If you can at all avoid shift/night work do so; if you cannot because of work requirements then discuss with your physician strategies to adjust and hopefully reduce the risk of serious heath disorders consequent to disruption of normal life rhythms.

An Optimal Diet?

An article on whether there is an optimal diet for weight management and metabolic health can be found here.

The bottom line is that while different types of diets may stress optimizing different health outcomes (low fat diets helping with LDL; low carb diets helping more with triglycerides and HDL), the main point is to adhere to a healthy diet.  Both low fat and low carb can work; people have different preferences, but if you are overweight, sticking to a diet that results in weight loss will improve many metrics of health and fitness.

Genome Editing In The (Mouse) Brain

Here is a paper from several years ago discussing a fascinating and very promising finding.  We'll need to take a look at any subsequent developments in this field as they have occurred or will occur. Abstract:

We demonstrate editing of post-mitotic neurons in the adult mouse brain following injection of Cas9 ribonucleoprotein (RNP) complexes in the hippocampus, striatum and cortex. Engineered variants of Cas9 with multiple SV40 nuclear localization sequences enabled a tenfold increase in the efficiency of neuronal editing in vivo. These advances indicate the potential of genome editing in the brain to correct or inactivate the underlying genetic causes of neurological diseases.

The ability o directly alter gene sequences in the adult brain can yield a vast array of therapeutic options for certain genetic neurological diseases.  An additional thing that will become necessary for certain of those diseases is the ability to therapeutically intervene, on  brain-wide level, at the protein level as well (e.g., misfolded protein disorders).

Fat Tissue miRNAs

Here is an article from several years ago that should raise some eyebrows, and we'll have to keep track of further developments in this field.  Abstract:

Adipose tissue is a major site of energy storage and has a role in the regulation of metabolism through the release of adipokines. Here we show that mice with an adipose-tissue-specific knockout of the microRNA (miRNA)-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, exhibit a substantial decrease in levels of circulating exosomal miRNAs. Transplantation of both white and brown adipose tissue-brown especially-into ADicerKO mice restores the level of numerous circulating miRNAs that are associated with an improvement in glucose tolerance and a reduction in hepatic Fgf21 mRNA and circulating FGF21. This gene regulation can be mimicked by the administration of normal, but not ADicerKO, serum exosomes. Expression of a human-specific miRNA in the brown adipose tissue of one mouse in vivo can also regulate its 3' UTR reporter in the liver of another mouse through serum exosomal transfer. Thus, adipose tissue constitutes an important source of circulating exosomal miRNAs, which can regulate gene expression in distant tissues and thereby serve as a previously undescribed form of adipokine.

So we have known for a long time that fat (adipose) tissue can release macromolecular factors (adipokines) that can affect metabolism of other tissues.  These adipokines may mediate some  of the negative health effects of obesity including an increased risk for cancer. MicroRNAs (miRNAs) are small RNA molecules that affect gene expression by binding to target mRNA and are this crucially important to both normal function and to disease.  Initially, it was thought that the miRNAs operated within the cell producing them, but later it was learned that miRNAs can be released by one cell to affect others (exosomal miRNAs).  This paper shows that fat tissue is an important source of such circulating miRNAs, demonstrating another mechanism by which fat tissue can affect metabolism of other parts of the body, contributing to human disease.

The harmful effects of overweight/obesity keep on growing.

Maternal Smoke Exposure And Cell Signaling

It is know that maternal smoke exposure can possibly cause problems to the fetus.  Here is a mouse study demonstrating that offspring of smoke-exposed pregnant female mice were underweight with deceased lung volume, and that there were alterations in important cell signaling pathways that may have caused the negative effects on the fetal mice  Abstract:

The present study tested the hypothesis that maternal smoke exposure results in fetal lung growth retardation due to dysregulation in various signaling pathways, including the Wnt (wingless-related integration site)/β-catenin pathway. Pregnant female C57BL/6J mice were exposed to cigarette smoke (100-150 mg/m3) or room air, and offspring were humanely killed on 12.5, 14.5, 16.5, and 18.5 d post coitum (dpc). We assessed lung stereology with Cavalieri estimation; apoptosis with proliferating cell nuclear antigen, TUNEL, and caspase assays; and gene expression with quantitative PCR (qPCR) and RNA sequencing on lung epithelium and mesenchyme retrieved by laser capture microdissection. Results demonstrated a significant decrease in body weight and lung volume of smoke-exposed embryos. At 16.5 dpc, the reduction in lung volume was due to loss of lung mesenchymal tissue correlating with a decrease in cell proliferation (n = 10; air: 61.65% vs. smoke: 44.21%, P < 0.05). RNA sequence analysis demonstrated an alteration in the Wnt pathway, and qPCR confirmed an increased expression of secreted frizzled-related protein 1 (sFRP-1) [n = 12; relative quantification (RQ) 1 vs. 2.33, P < 0.05] and down-regulation of Cyclin D1 (n = 7; RQ 1 vs. 0.61, P < 0.05) in mesenchymal tissue. Furthermore, genome expression studies revealed a smoke-induced up-regulation of Rho-GTPase-dependent actin cytoskeletal signaling that can lead to loss of tissue integrity.-Unachukwu, U., Trischler, J., Goldklang, M., Xiao, R., D'Armiento, J. Maternal smoke exposure decreases mesenchymal proliferation and modulates Rho-GTPase-dependent actin cytoskeletal signaling in fetal lungs.

The importance of pregnant women avoiding maternal smoke exposure is underlined with this study.

Wnt Signaling And TB

Here is an interesting paper from several years ago discussing a potential link between a signaling pathway more commonly associated with (colorectal) cancer and the immune response to tuberculosis. Abstract:

Mycobacterium tuberculosis (M. tuberculosis), an intracellular pathogenic Gram-positive bacterium, is the cause of tuberculosis (TB), a major worldwide human infectious disease. The innate immune system is the first host defense against M. tuberculosis. The recognition of this pathogen is mediated by several classes of pattern recognition receptors expressed on the host innate immune cells, including Toll-like receptors, Nod-like receptors, and C-type lectin receptors like Dectin-1, the Mannose receptor, and DC-SIGN. M. tuberculosis interaction with any of these receptors activates multiple signaling pathways among which the protein kinase C, the MAPK, and the NFκB pathways have been widely studied. These pathways have been implicated in macrophage invasion, M. tuberculosis survival, and impaired immune response, thus promoting a successful infection and disease. Interestingly, the Wnt signaling pathway, classically regarded as a pathway involved in the control of cell proliferation, migration, and differentiation in embryonic development, has recently been involved in immunoregulatory mechanisms in infectious and inflammatory diseases, such as TB, sepsis, psoriasis, rheumatoid arthritis, and atherosclerosis. In this review, we present the current knowledge supporting a role for the Wnt signaling pathway during macrophage infection by M. tuberculosis and the regulation of the immune response against M. tuberculosis. Understanding the cross talk between different signaling pathways activated by M. tuberculosis will impact on the search for new therapeutic targets to fuel the rational design of drugs aimed to restore the immunological response against M. tuberculosis.

Once again, the importance of basic science research is seen.  First, the Wnt pathway was studied as a model of cell signaling, including in the fruit fly model.  Then, the absolute importance of this pathway in cancer, particularly colorectal cancer, was determined.  Next, Wnt signaling was identified as important in many other disorders, including neurodegenerative, and now has important implications in infectious disease.

Gene Editing For Muscular Dystrophy

Here is a paper from several years ago discussing promising results with gene therapy in a mouse model of muscular dystrophy.  Abstract:

Gene replacement therapies utilizing adeno-associated viral (AAV) vectors hold great promise for treating Duchenne muscular dystrophy (DMD). A related approach uses AAV vectors to edit specific regions of the DMD gene using CRISPR/Cas9. Here we develop multiple approaches for editing the mutation in dystrophic mdx4cv mice using single and dual AAV vector delivery of a muscle-specific Cas9 cassette together with single-guide RNA cassettes and, in one approach, a dystrophin homology region to fully correct the mutation. Muscle-restricted Cas9 expression enables direct editing of the mutation, multi-exon deletion or complete gene correction via homologous recombination in myogenic cells. Treated muscles express dystrophin in up to 70% of the myogenic area and increased force generation following intramuscular delivery. Furthermore, systemic administration of the vectors results in widespread expression of dystrophin in both skeletal and cardiac muscles. Our results demonstrate that AAV-mediated muscle-specific gene editing has significant potential for therapy of neuromuscular disorders.

That's very promising.  What's going on more recently? Future posts here will explore the progress in this and other similar projects using gene therapy tested in mouse models. This is why basic science research is so important, as the methods utilized are ultimately derived from such research.

Melatonin For Resistance-Training Athletes

Can melatonin have beneficial effects for athletes other than on circadian rhythms?  This paper says yes.  Abstract:

Previous data showed that the administration of high doses of melatonin improved the circadian system in athletes. Here, we investigated in the same experimental paradigm whether the antioxidant properties of melatonin has also beneficial effects against exercise-induced oxidative stress and muscle damage in athletes. Twenty-four athletes were treated with 100 mg.day-1 of melatonin or placebo 30 min before bedtime during four weeks in a randomized double-blind scheme. Exercise intensity was higher during the study that before starting it. Blood samples were collected before and after treatment, and plasma was used for oxygen radical absorption capacity (ORAC), lipid peroxidation (LPO), nitrite plus nitrate (NOx), and advanced oxidation protein products (AOPP) determinations. Glutathione (GSH), glutathione disulphide (GSSG) levels, and glutathione peroxidase (GPx) and reductase (GRd) activities, were measured in erythrocytes. Melatonin intake increased ORAC, reduced LPO and NOx levels, and prevented the increase of AOPP, compared to placebo group. Melatonin was also more efficient than placebo in reducing GSSG.GSH-1 and GPx.GRd-1 ratios. Melatonin, but not placebo, reduced creatine kinase, lactate dehydrogenase, creatinine, and total cholesterol levels. Overall, the data reflect a beneficial effect of melatonin treatment in resistance-training athletes, preventing extra- and intracellular oxidative stress induced by exercise, and yielding further skeletal muscle protection against exercise-induced oxidative damage.

This, melatonin seems to protect skeletal muscle from oxidative stress damage as it prevents extracellular and intracellular oxidative stress. Interestingly, total cholesterol was reduced as well.

Theraband Use Youtube Video

The Theraband (see it at Amazon) is a useful exercise tool that some people have utilized for injury rehabilitation, particularly for elbow problems

A YouTube video discussing the product can be seen here.

Metaphoric Language In Romance

Here is a paper appropriate for Valentine's Day.  Abstract:

Language plays an important role in romantic attachment. However, it is unclear whether the structure and topic of language use might influence potential mate choice. We investigated 124 female students' preference for compliments paid by males incorporating either literal or metaphoric (conventional/novel) language and targeting their appearance or possessions (house) throughout their menstrual cycle. Male faces paired with novel metaphorical compliments were rated as more attractive by women than those paired with literal ones. Compliments targeting appearance increased male attractiveness more than possessions. Interestingly, compliments on appearance using novel metaphors were preferred by women in a relationship during the fertile phase but by single women during the luteal phase. A similar pattern of altered face attraction ratings was subsequently shown by subjects in the absence of the verbal compliments and even though they were unable to recognize the faces. Thus the maintained attraction bias for faces previously associated with figurative language compliments appears to be unconscious. Overall this study provides the first evidence that women find men who typically use novel metaphorical language to compliment appearance more attractive than those using prosaic language or complimenting possessions. The evolutionary significance for such a language use bias in mate selection is discussed.

That is an interesting study in human psychology and mate attraction.

Elimination Diets For Neurodevelopmental Disorders.

Elimination diets attempt to identity foods that cause certain symptoms or disorders.  Here is a paper that focuses on elimination diets as interventions for, e.g., attention deficit hyperactivity disorder and autism spectrum disorder.  Abstract:

Nutrition plays an important role in neurodevelopment. This insight has led to increasing research into the efficacy of nutrition-related interventions for treating neurodevelopmental disorders. This review discusses an elimination diet as a treatment for attention deficit hyperactivity disorder and autism spectrum disorder, with a focus on the efficacy of the food additives exclusion diet, gluten-free/casein-free diet and oligoantigenic diet. Furthermore, we discuss the potential mechanisms of elimination diets' effects in these neurodevelopmental disorders. The main candidate mechanism is the microbiome-gut-brain axis possibly involving complex interactions between multiple systems, including the metabolic, immune, endocrine, and neural system. We conclude with practical implications and future directions into the investigation of an elimination diet's efficacy in the treatment of attention deficit hyperactivity disorder and autism spectrum disorder.

Once again we see the power of nutrition and diet to affect serious human health and developmental problems, and we note the mention of "the microbiome-gut-brain axis" - demonstrating, also once again, the relevance of the gut microbiome to various aspects of human well-being.