The aim was to provide an overview of chronic low-grade inflammatory phenotype (CLIP) and evidence for its role in the pathogenesis of frailty and other chronic conditions as well as potential ...causative factors and interventions.
We reviewed evidence from published clinical and laboratory studies and summarized the opinions of experts from published reviews.
CLIP is a low-grade, systemic, unresolved, and smoldering chronic inflammatory state clearly indicated by a 2- to 4-fold increase in serum levels of inflammatory mediators, such as interleukin-6 and C-reactive protein. It involves many other cellular and molecular inflammatory mediators. CLIP typically occurs during aging, also known as “inflammaging,” and is an integral part of the spectrum of immunosenescence. Causative factors likely include persistent viral infections, particularly chronic cytomegalovirus infection, cellular senescence, failure to eliminate degraded materials and waste products, dysregulated microbiota and gut permeability, obesity, and others. Substantial evidence supports CLIP as a powerful contributing factor to frailty and many other chronic conditions and adverse health outcomes. Many of the inflammatory mediators and their regulatory mechanisms in CLIP may serve as potential targets for therapeutic intervention. However, development of new interventional strategies for CLIP and its associated chronic conditions should take the complexity of the inflammatory network into consideration. Nonpharmacologic interventions, such as caloric restriction and exercise, may have significant impact on CLIP and its causative factors, leading to substantial health benefits. Metformin and resveratrol have anti-inflammatory property and may serve as a promising therapeutic agent for treatment of CLIP and frailty.
CLIP is a chronic inflammatory pathophysiologic process that plays an important role in the pathogenesis of frailty and many other chronic conditions. Improving our understanding of this phenotype may provide opportunities to identify potential targets of effective prevention and therapeutic strategies for frailty and other CLIP-associated conditions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Cellulose was prepared from agricultural waste corn stover.•The cellulose size was reduced by mechanical shearing through homogenization.•The cellulose nanofibril (CNF) can be obtained by repeat ...homogenization shearing.•The cellulose films without shearing exhibited weaker mechanical properties.•The cellulose nanofibril (CNF) films exhibited stronger mechanical properties.
Agricultural waste corn stover has little economic value. Cellulose was extracted from corn stover by the processes of alkali treatment and delignification, resulting in a > 93% purity. The particle size of the extracted cellulose was reduced by mechanical shearing through high pressure homogenization. When passing through a homogenizer thirty times, the cellulose nanofibril (CNF) can be obtained. The diameters of the CNF ranged between 5 and 50 nm, and the lengths were microns. The mechanical properties of the films, made by corn stover cellulose, with and without high pressure homogenization shearing were evaluated using an Instron instrument. The films made by cellulose without shearing exhibited weaker mechanical properties, while the CNF films exhibited stronger mechanical properties. The linear rheological properties of CNF suspensions were also investigated and results show solid-like viscoelastic behavior. Our findings regarding corn stover CNF are similar to those CNF from other sources reported in the literature.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•Soybeans obtained from many 2013-2016 production locations around the United States.•Analysis of total isoflavone and total saponin quantification performed by HPLC.•Preprocessing algorithms were ...applied to NIRS spectra to minimize variation.•Multiple Linear Regression based models predict isoflavone content.•Predictions had high regression coefficients, low standard errors of calibration.
Over 3200 discrete soybean samples were obtained from production locations around the United States during the years 2012–2016. Ground samples were scanned on near infrared spectrometers (NIRS) and analyzed by HPLC for total isoflavone and total saponin composition, as well as total carbohydrate composition. Multiple Linear Regression (MLR) analysis of preprocessed spectral data was used to develop optimized models to predict isoflavone content. The selection of a suitable calibration model was based on a high regression coefficient (R2), and lower standard error of calibration (SEC) values. Robust validated predictions were obtained for isoflavones, however less than robust calibrations were obtained for the total saponins. The correlations were not as robust for predicting the carbohydrate composition. NIRS is a suitable, rapid, nondestructive method to determine isoflavone composition in ground soybeans. Useful isoflavone composition predictions for large numbers of soybean samples can be obtained from quickly obtained NIRS scans.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Enhancers play important roles in controlling gene expression in a choreographed spatial and temporal manner during development. However, it is unclear how these regulatory regions are ...established during differentiation. Here we investigated the genome-wide binding profile of the forkhead transcription factor FOXK2 in human embryonic stem cells (ESCs) and downstream cell types. This transcription factor is bound to thousands of regulatory regions in human ESCs, and binding at many sites is maintained as cells differentiate to mesendodermal and neural precursor cell (NPC) types, alongside the emergence of new binding regions. FOXK2 binding is generally associated with active histone marks in any given cell type. Furthermore newly acquired, or retained FOXK2 binding regions show elevated levels of activating histone marks following differentiation to NPCs. In keeping with this association with activating marks, we demonstrate a role for FOXK transcription factors in gene activation during NPC differentiation. FOXK2 occupancy in ESCs is therefore an early mark for delineating the regulatory regions, which become activated in later lineages.
The identification and validation of drugs that promote health during aging (“geroprotectors”) are key to the retardation or prevention of chronic age‐related diseases. Here, we found that most of ...the established pro‐longevity compounds shown to extend lifespan in model organisms also alter extracellular matrix gene expression (i.e., matrisome) in human cell lines. To harness this observation, we used age‐stratified human transcriptomes to define the age‐related matreotype, which represents the matrisome gene expression pattern associated with age. Using a “youthful” matreotype, we screened in silico for geroprotective drug candidates. To validate drug candidates, we developed a novel tool using prolonged collagen expression as a non‐invasive and in‐vivo surrogate marker for Caenorhabditis elegans longevity. With this reporter, we were able to eliminate false‐positive drug candidates and determine the appropriate dose for extending the lifespan of C. elegans. We improved drug uptake for one of our predicted compounds, genistein, and reconciled previous contradictory reports of its effects on longevity. We identified and validated new compounds, tretinoin, chondroitin sulfate, and hyaluronic acid, for their ability to restore age‐related decline of collagen homeostasis and increase lifespan. Thus, our innovative drug screening approach—employing extracellular matrix homeostasis—facilitates the discovery of pharmacological interventions promoting healthy aging.
We correlated extracellular matrix gene expression signatures (matreotypes) corresponding to young and old human tissues with drug‐treated expression profiles to predict longevity drugs. Then, we established Caenorhabditis elegans collagen homeostasis as a novel surrogate marker of longevity as the first pass for in‐vivo screening. We validated candidates via lifespan assays and identified new geroprotective drugs.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Organogels obtained from plant wax and soybean oil were tested for their suitability for incorporation into margarine. Sunflower wax, rice bran wax and candelilla wax were evaluated. Candelilla wax ...showed phase separation after making the emulsion with the formulation used in this study. Rice bran wax showed relatively good firmness with the organogel, but dramatically lowered firmness for a margarine sample. Sunflower wax showed the greatest firmness for organogel and the margarine samples among the three plant waxes tested in this study. Firmness of the margarine containing 2–6 % sunflower wax in soybean oil was similar to that of margarine containing 18–30 % hydrogenated soybean oil in soybean oil. The firmness of commercial spread could be achieved with about 2 % sunflower wax and that of commercial margarine could be achieved with about 10 % of sunflower wax in the margarine formulation. Dropping point, DSC and solid fat content of the new margarine containing 2–6 % sunflower wax showed a higher melting point than commercial margarine and spreads.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Skeletal muscle Na
+
channels possess Ca
2+
- and calmodulin-binding sites implicated in Nav1.4 current (
I
Na
) downregulation following ryanodine receptor (RyR1) activation produced by ...exchange protein directly activated by cyclic AMP or caffeine challenge, effects abrogated by the RyR1-antagonist dantrolene which itself increased
I
Na
. These findings were attributed to actions of consequently altered cytosolic Ca
2+
, Ca
2+
i
, on Na
v
1.4. We extend the latter hypothesis employing cyclopiazonic acid (CPA) challenge, which similarly increases Ca
2+
i
, but through contrastingly inhibiting sarcoplasmic reticular (SR) Ca
2+
-ATPase. Loose patch clamping determined Na
+
current (
I
Na
) families in intact native murine gastrocnemius skeletal myocytes, minimising artefactual Ca
2+
i
perturbations. A bespoke flow system permitted continuous
I
Na
comparisons through graded depolarizing steps in identical stable membrane patches before and following solution change. In contrast to the previous studies modifying RyR1 activity, and imposing control solution changes, CPA (0.1 and 1 µM) produced persistent increases in
I
Na
within 1–4 min of introduction. CPA pre-treatment additionally abrogated previously reported reductions in
I
Na
produced by 0.5 mM caffeine. Plots of peak current against voltage excursion demonstrated that 1 µM CPA increased maximum
I
Na
by ~ 30%. It only slightly decreased half-maximal activating voltages (
V
0.5
) and steepness factors (
k
), by 2 mV and 0.7, in contrast to the
V
0.5
and
k
shifts reported with direct RyR1 modification. These paradoxical findings complement previously reported downregulatory effects on Nav1.4 of RyR1-agonist mediated
increases
in
bulk
cytosolic Ca
2+
. They implicate possible
local
tubule-sarcoplasmic triadic domains containing
reduced
Ca
2+
TSR
in the observed upregulation of Nav1.4 function following CPA-induced SR Ca
2+
depletion.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
It was previously reported that sunflower wax (SW) had high potential as an organogelator for soybean oil–based margarine and spread products. In this study, 12 other vegetable oils were evaluated in ...a margarine formulation to test feasibility of utilization of SW as an alternative to solid fats in margarine and spread products containing these oils. The minimum quantity of SW required to form a gel with these oils ranged from 0.3% to 1.0% (wt.). Organogels were prepared from the vegetable oils with 3%, 5% and 7% SW and were tested for firmness as well as melting behaviors using differential scanning calorimetry. These organogels were also incorporated into a margarine formulation. All of the vegetable oil organogels produced relatively firm margarines. The margarines prepared from organogels containing 3% (wt.) SW had greater firmness than commercial spreads, whereas margarines made from 7% SW were softer than commercial stick margarines. However, dropping points of the margarine samples were higher than those of commercial spread and margarine products. Margarine firmness was modestly inversely correlated with the amount of polar compounds in the oils and did not correlate with fatty acid compositions. This study demonstrates the feasibility of using a number of healthy vegetable oils rich in polyunsaturated fatty acids to make healthy margarine and spread products by utilizing SW as an organogelator.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Elderly atopic dermatitis (AD) is a subtype of AD defined by age (≥ 60 years). The molecular characteristics of elderly AD remain to be clarified.
We sought to characterize the molecular features of ...skin lesions and peripheral blood mononuclear cells (PBMCs) in patients with AD across different age, focusing on elderly AD.
Skin and PBMCs samples were used for RNA sequencing. Analysis of differentially expressed genes and gene set variation analysis were performed. Immunofluorescence staining, quantitative real-time PCR (qRT-PCR), flow cytometry and transwell assay were used for validation.
Compared with healthy controls, the skin transcriptome of AD patients showed common signatures of AD, like barrier dysfunction and enhanced Th1/Th2/Th17 immune pathways. In PBMCs, the expression of Th1/Th2 response genes was more remarkable in adult AD, while expression of Th17-related genes was significantly higher in childhood AD. The gene modules associated with natural killer (NK) cells were downregulated in elderly AD. In skin lesions, elderly AD exhibited enrichment of macrophages, fibroblasts and senescence-associated secretory phenotype (SASP) related genes. The correlation among fibroblasts, SASP and innate immune cells were revealed by the co-localization of fibroblasts, macrophages and NK cells in the lesions across different age groups. Fibroblasts under inflammation or senescence could induce stronger chemotaxis of macrophages and NK cells.
We identified the molecular phenotypes of skin lesions and PBMCs in elderly AD individuals. Fibroblasts, innate immune cells, and SASP might play important roles in the pathogenesis of elderly AD.
•Elderly patients with AD present distinct transcriptomic characteristics.•Senescent fibroblasts may be the main source of SASP.•Senescent fibroblasts induce cascade activation of innate immune cells and are involved in the pathogenesis of elderly AD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aim of this study is to evaluate the oleogel (or organogel) technology as a new method to prevent oxidation of fish oil by immobilizing oil and to provide useful information on oxidation of ...oleogels for their application in actual food products. Four different natural waxes, rice bran wax, sunflower wax, candelilla wax, and beeswax are used to prepare fish oil oleogels. Peroxide value, conjugated diene value, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are measured after storing oleogels at 35 and 50 °C, respectively. All 3% wax‐fish oil oleogels shows slower oxidation than the bulk fish oil at 35 °C. Beeswax is not as effective as other waxes during storage at 50 °C due to its lower melting point. The color penetration measurement method is developed as a convenient method to predict the oxidation rate of oleogel. Cooling oleogel at a faster rate can significantly reduce the oxidation rate of the oleogel. A larger amount of wax is not recommended to increase the protective effect, which can give a negative effect due to the prooxidant activity of wax. The oleogel technology may be applied to reduce oxidation of food products and nutritional supplements containing omega‐3 oil.
Practical Application: This study clearly shows that the oleogel technology can be used to prevent oil oxidation by immobilizing oil in food products. This technology can be used for commercial products such as fish oil supplements to prevent oil oxidation during production, transportation, and storage. The information presented in this study can also be used for new omega‐3 oil fortified food products such as margarine, spreads, shortening, cookies, and other related products. The oleogel technology can be easily applied as a drop‐in method. Natural waxes used as oleogelator are inexpensive and widely available, and most of them are already used in many food products.
Peroxide value of 3% wax‐fish oil oleogels stored at 35 °C for 7 days.
Peroxide value of 3% wax‐fish oil oleogels stored at 35 °C for 7 days.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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