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Background: The discovery of the nod-like receptor protein (NLRP) inflammasomes in 2002 has led to the rapid identification of these unique cellular proteins as key targets for studies on innate inflammation pathways. The NLRP inflammasomes have been shown to be expressed in normal human epidermal keratinocytes (NHEK) and human dermal fibroblasts (HDF). NLRP inflammasomes in keratinocytes are interesting as these skin cells are the first living cells in the skin to contact external exogenous threats such as UV energy, chemicals, physical trauma, and bacteria and viruses. Activation of the NLRP Inflammasomes by exogenous threats results in the release of active Caspase-1 (ACasp-1), a key protease enzyme, which targets inactive forms of IL-1β, IL-18 as well as IL-1α and IL-33. Purpose: This article discusses efforts to examine the release of active Caspase-1 from NHEKs activated by various exogenous threats including UVB energy, ATP, Nigericin and Urban Dust. The work further examines if, after inflammasome activation and Caspase-1 release, certain naturally derived botanical ingredients known to have anti-inflammatory effects can function to inhibit upregulation of active Caspase-1. Methods: NHEK were treated with various doses of UVB, ATP and Nigericin and with a single dose of Urban Dust. ACasp-1 expression was measured after 3 and 20 hours using the Promega Caspase Glo-1 bioluminescent assay. After confirmation that 60 mJ/cm 2 of UVB and 5mM of ATP were effective to activate NHEK ACasp-1 release after 20 hrs, these conditions were employed to examine the influence of three botanical blends of ingredients on their ability to inhibit ACasp-1 expression. Results: Initial results demonstrate that NHEKs can be activated to release active Caspase-1 by ATP and UVB, but not by Nigericin or Urban Dust. In addition, it was unexpectedly found that, while ATP and UVB activated NHEKs, the release of ACasp-1-did not happen within the first 3 hours after exposure but did become significant after 20 hours. Additional results indicate that a blend of polysaccharides and two blends of antioxidants, one oilsoluble and the other water-soluble, known for their anti-inflammatory effects, can reduce expression of active Caspase-1 in activated NHEKs when applied extracellularly. Conclusion: Expression of NLRP activated release of ACasp-1 was found to be influenced by UVB and ATP but not by Nigericin or Urban Dust. The effects were also time dependent. Several botanical extract blends were found to reduce ACasp-1 expression in previously activated NHEKs. Links between these inflammatory effects and processes of cellular inflammaging are discussed.

We examined the evidence for greater fat utilization by women during exercise and the potential gender differences in specific cellular processes. Results from well-controlled studies show that, compared to men, women oxidize more fat during submaximal exercise, resulting in the relative sparing of muscle glycogen. Mature female rats use less muscle glycogen during running and can run longer than male counterparts. Circulating estrogen is critical to these observations, as shown by studies where male rats were treated with estrogen. Estrogen-treated male rats use less muscle glycogen during exercise and can run longer than untreated males. The cellular mechanisms and factors underlying these findings are unknown and certainly multifactorial. We offer some information that, unfortunately, does not lead to any natural conclusion. However, this area is certainly ripe for research.

The purpose of this study was to determine the effect of 12 wks of aerobic training on resting lymphocyte number and proliferation, and immunoglobulin and cytokine levels. Eleven college-aged males (training group = EX) performed 30 min of cycling at 75% of VO2peak, 3 days/wk with VO2peak assessment and blood samples taken at 0,8 and 12 wks. A group of 10 sedentary controls (CT) underwent the same testing protocol. Lymphocyte proliferation response to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) was quantified as a stimulation index (SI) based on the ratio of stimulated versus control cultures, and as total counts per min (CPM). Immunoglobulin (Ig) levels (IgG, IgA, and IgM), and lymphocyte counts were also determined. There was a significant increase in VO2 in the EX group (41.0 +/- 1.8 vs. 46.3 +/- 1.4 ml.kg-1.min-1 pre and post training, respectively). Training had no effect on the PHA SI for the EX group (23.9 +/- 3.3, 27.7 +/- 4.1, and 26.3 +/- 4.0 at 0, 8 and 12 wks, respectively), or the responses of the CT group (28.8 +/- 6.0, 23.9 +/- 3.1, and 30.6 +/- 4.3). No changes were observed for the PWM SI. Significant increases were observed in the CPM for both groups. No differences in the Ig or lymphocyte levels were found during the study. These data indicate that 12 wks of moderate endurance training did not alter resting immune function as determined by mitogen stimulated lymphocyte proliferation, total circulating lymphocytes, or Ig levels.

The primary purpose of the study was to compare maximal accumulated oxygen deficit (MAOD) in resistance-trained (RT), endurance-trained (ET), and untrained men (UT). A secondary purpose was to determine the influence of leg muscle mass (MM) on MAOD by examining the relationship between MM and MAOD and by comparing MAOD expressed relative to MM between the groups. MAOD was determined during 2-4 min of constant-load fatiguing cycling. MM, estimated via anthropometric measurements, was higher (p < .05) for RT (mean +/- SE; 25.5 +/- 3.4 kg) compared to ET (20.3 +/- 3.5) and UT (21.6 +/- 3.4). MAOD in liters O2eq was larger in RT (4.75 +/- 0.3) compared to UT (3.07 +/- 0.3) and ET (3.75 +/- 0.3). A significant positive correlation was observed between MAOD (LO2eq) and MM (kg) for RT only (RT, r = .85; ET, r = .55; UT, r = .20). Based on the correlational and mean MM data, the higher MAOD (LO2eq) in RT relative to ET and UT is predominantly the result of their larger leg muscle mass.

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Objective: Exposure to certain stresses in small doses might lead to a protective effect by improving resistance to other stressors. Dead Sea (DS) minerals can be a relevant source to induce positive stress due to their high salinity and unique mineral combination. This concept could be further optimized using advanced unique cell biotechnology. The purpose of this study was to elucidate the innovative concept of DS minerals (water extract and black mud) supplementation in small amount to Pichia pastoris yeast growth media as a positive stress by testing the capability of accepted fermentation compounds to affect the appearance of skin. Methods: Skin equivalents were topically applied with different Pichia pastoris fermentations (Metabiotics™). Skin elasticity biomarkers were tested, since loss of elasticity and suppleness is a natural skin aging process leading to deeper wrinkles and loss of firmness. A preliminary screening at the gene level using DNA microarray was performed and subsequently, the following proteins were detected using ELISA or immunoblotting assays: elastin, fibulin-1, lysyl oxidase (LOX), metalloproteinase 3 (MMP-3), E-cadherin, claudin 4, tight junction protein (TJP)-1 and TJP-2. UVB irradiation was selected as a stressor. Results: Fermentation compounds generated in the presence of small doses of DS minerals affected the expression of various elasticity-related genes in skin. Moreover, they significantly attenuated the abnormal UVB-induced alterations, the proteins elastin, fibulin-1, LOX, MMP-3, E-cadherin and TJP-2. Conclusions: The observations clearly demonstrate that when DS Metabiotics™ compounds are topically applied, significant alterations in several biomarkers that contribute to skin elasticity occur. Thus, these novel compounds have the potential to serve as skincare actives.

A series of well-known, purified antioxidants including: Resveratrol, Epigallocatechin Gallate (EGCG), Genistein, Rosavin, Puerarin, Chlorogenic Acid, Propolis and two newer unexplored isoflavonoids isolated from Maclura pomifera (Osage Orange) including Pomiferin and Osajin, were applied to Normal Human Dermal Fibroblasts (NHDF) and Normal Human Dermal Keratinocytes (NHEK) for 24 hours. The resulting treated cells were then examined using human gene microarrays supplied by Agilent. These chips typically have somewhere on the order of 30,000 individual genes which are expressed in the human genome. For our study, this large list of genes was reduced to 205 principal genes thought to be important for skin and each individual ingredient was examined for its influence on the culled list of genes. Working on a hypothesis that there may be some common genes which are either upregulated or downregulated by all or most of these ingredients, a short list of genes for each cell line was developed. What appears to emerge from these studies is that several genes in the gene pool that was screened are influenced by most or all of the molecules of interest. Genes that appear to be upregulated in both cell lines by all the ingredients include: ACLY, AQP3, COX1, NOS3, and PLOD3. Genes that appear to be downregulated in both cell lines by all ingredients include only PGR.