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.

Saline Infusion For Postural Tachycardia Syndrome

Treatment for option for postural tachycardia syndrome described here, abstract:

BACKGROUND: The postural tachycardia syndrome (POTS) is a heterogeneous group of disorders that results in symptoms of orthostatic intolerance. Excess blood pooling has been observed to cause low effective circulating volume in the central vasculature. Consequently, acute volume loading with IV saline has emerged as a potential strategy for clinical intervention. We evaluated the impact of acute volume loading on both the signs and symptoms of patients suffering from POTS.

METHODS: Fifty-seven subjects screened from our population of POTS patients and assenting to participation were administered the two surveys by telephone. Subjects completed each survey twice, before, and after initiating IV hydration therapy. The Orthostatic Hypotension Questionnaire (OHQ) was used to assess change in clinical symptomatology, while the short form 36 health survey (SF-36) was employed to assess the impact of IV saline infusion on quality of life.
RESULTS: Fifty-seven patients were included in the analysis. The average number of medications trialed before referral for IV hydration was 3.6 ± 1.7 medications. Saline infusions occurred with mean frequency of 11.3 ± 8.5 days and at a mean volume of 1.5 ± 0.6 l per infusion. The mean change of the OHQ was 3.1 ± 0.3 (95% CI 2.6-3.7; P < 0.001), with significant improvement in all the composite scores. The mean change in the SF-36 form was 19.1 ± 2.7 (95% CI -24.6 to -13.6; P < 0.001).
CONCLUSIONS: Intermittent IV infusions of saline dramatically reduce symptoms and improve quality of life in patients suffering from POTS. Further work should explore its efficacy as a bridge study for patients of high symptomatic severity.

So, something simple such as saline infusion can have a significant positive impact on the symptoms of this disorder; this may be something patients afflicted with this syndrome should discuss with their physicians.