Urodele amphibians are unique among adult vertebrates in their ability to regenerate complex body structures after traumatic injury. In salamander regeneration, the cells maintain a memory of their original position and use this positional information to recreate the missing pattern. We used an in vivo gain‐of‐function assay to determine whether components of the extracellular matrix (ECM) have positional information required to induce formation of new limb pattern during regeneration. We discovered that salamander limb ECM has a position‐specific ability to either inhibit regeneration or induce de novo limb structure, and that this difference is dependent on heparan sulfates that are associated with differential expression of heparan sulfate sulfotransferases. We also discovered that an artificial ECM containing only heparan sulfate was sufficient to induce de novo limb pattern in salamander limb regeneration. Finally, ECM from mouse limbs is capable of inducing limb pattern in axolotl blastemas in a position‐specific, developmental‐stage‐specific, and heparan sulfate‐dependent manner. This study demonstrates a mechanism for positional information in regeneration and establishes a crucial functional link between salamander regeneration and mammals.
Knee osteoarthritis (OA) is a common degenerative joint disease which contributes significantly to the burden of physical disability. Conventional management of OA mainly focuses on relief of symptoms using analgesics and non-steroidal anti-inflammatory drugs (NSAIDs). Some dietary supplements have shown some potency to reduce symptoms associated with OA conditions. Calcium Fructoborate (commercially marketed under the trade name FruiteX-B®), is a naturally occurring borate complex as first described by Patrick Brown [1]. For this study, FruiteX-B® was characterized by NMR and data from solid and liquidstate 11 B NMR have been obtained and compared against boric acid and fructose for quality purposes. In this study, FruiteX-B® was tested for fourteen days at a serving of 108 mg twice a day on subjects diagnosed with minor osteoarthritis conditions of the knees by CT scan. FruiteX-B® was well tolerated by all study subjects with no reports of adverse effect and resulted in several positive outcomes. On Day 14, WOMAC and McGill indexes were reduced by an average 29% and 14% respectively over Day 1 pre-ingestion values. Blood level of C-Reactive Protein (CRP) in 7 out of 10 subjects was found reduced up to 37% compared to Day 1 baseline levels. Interestingly, the study also showed that blood level of endogenous 1, 25(OH) vitamin D was increased more than 19% compared to baseline. However, differences in 25(OH) vitamin D were not observed. These results indicate that FruiteX-B® at a serving as low as 108mg twice a day provides significant benefits to people experiencing conditions associated with knee osteoarthritis. On the basis of these results, a larger clinical efficacy study is highly justified.
The present single-dose study was performed to assess the effect of whole coffee fruit concentrate powder (WCFC), green coffee caffeine powder (N677), grape seed extract powder (N31) and green coffee bean extract powder (N625) on blood levels of brain-derived neurotrophic factor (BDNF). Randomly assorted groups of fasted subjects consumed a single, 100 mg dose of each material. Plasma samples were collected at time zero (T 0 ) and at 30 min intervals afterwards, up to 120 min. A total of two control groups were included: subjects treated with silica dioxide (as placebo) or with no treatment. The collected data revealed that treatments with N31 and N677 increased levels of plasma BDNF by about 31 % under these experimental conditions, whereas treatment with WCFC increased it by 143 % (n 10), compared with baseline. These results indicate that WCFC could be used for modulation of BDNF-dependent health conditions. However, larger clinical studies are needed to support this possibility.
The maintenance of cellular function relies on the close regulation of adenosine triphosphate (ATP) synthesis and hydrolysis. ATP hydrolysis by mitochondrial ATP Synthase (CV) is induced by loss of proton motive force and inhibited by the mitochondrial protein ATPase inhibitor (ATPIF1). The extent of CV hydrolytic activity and its impact on cellular energetics remains unknown due to the lack of selective hydrolysis inhibitors of CV. We find that CV hydrolytic activity takes place in coupled intact mitochondria and is increased by respiratory chain defects. We identified (+)-Epicatechin as a selective inhibitor of ATP hydrolysis that binds CV while preventing the binding of ATPIF1. In cells with Complex-III deficiency, we show that inhibition of CV hydrolytic activity by (+)-Epichatechin is sufficient to restore ATP content without restoring respiratory function. Inhibition of CV-ATP hydrolysis in a mouse model of Duchenne Muscular Dystrophy is sufficient to improve muscle force without any increase in mitochondrial content. We conclude that the impact of compromised mitochondrial respiration can be lessened using hydrolysis-selective inhibitors of CV.
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