Premature loss of ovarian function (POI) is associated with numerous negative side effects, including vasomotor symptoms, sleep and mood disturbances, disrupted urinary function, and increased risks ...for osteoporosis and heart disease. Hormone replacement therapy (HRT), the standard of care for POI, delivers only a subset of ovarian hormones and fails to mimic the monthly cyclicity and daily pulsatility characteristic of healthy ovarian tissue in reproductive-aged individuals whose ovarian tissue contains thousands of ovarian follicles. Ovarian tissue allografts have the potential to serve as an alternative, cell-based HRT, capable of producing the full panel of ovarian hormones at physiologically relevant doses and intervals. However, the risks associated with systemic immune suppression (IS) required to prevent allograft rejection outweigh the potential benefits of comprehensive and dynamic hormone therapy. This work investigates whether the age of ovarian tissue donor animals affects the function of, and immune response to, subcutaneous ovarian grafts. We performed syngeneic and semi-allogeneic ovarian transplants using tissue from mice aged 6-8 (D7) or 20-22 (D21) days and evaluated ovarian endocrine function and immune response in a mouse model of POI. Our results revealed that tissue derived from D7 donors, containing an ample and homogeneous primordial follicle reserve, was more effective in fully restoring hypothalamic-pituitary-ovarian feedback. In contrast, tissue derived from D21 donors elicited anti-donor antibodies with higher avidity compared to tissue from younger donors, suggesting that greater immunogenicity may be a trade-off of using mature donors. This work contributes to our understanding of the criteria donor tissue must meet to effectively function as a cell-based HRT and explores the importance of donor age as a factor in ovarian allograft rejection.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective. Hydrogel scaffolds hold promise for a myriad of tissue engineering applications, but often lack tissue-mimetic architecture. Therefore, in this work, we sought to develop a new technology ...for the incorporation of aligned tubular architecture within hydrogel scaffolds engineered from the bottom-up. Approach. We report a platform fabrication technology-magnetic templating-distinct from other approaches in that it uses dissolvable magnetic alginate microparticles (MAMs) to form aligned columnar structures under an applied magnetic field. Removal of the MAMs yields scaffolds with aligned tubular microarchitecture that can promote cell remodeling for a variety of applications. This approach affords control of microstructure diameter and biological modification for advanced applications. Here, we sought to replicate the microarchitecture of the native nerve basal lamina using magnetic templating of hydrogels composed of glycidyl methacrylate hyaluronic acid and collagen I. Main results. Magnetically templated hydrogels were characterized for particle alignment and micro-porosity. Overall MAM removal efficacy was verified by 96.8% removal of iron oxide nanoparticles. Compressive mechanical properties were well-matched to peripheral nerve tissue at 0.93 kPa and 1.29 kPa, respectively. In vitro, templated hydrogels exhibited approximately 36% faster degradation over 12 h, and were found to guide axon extension from dorsal root ganglia. Finally, in a pilot in vivo study utilizing a 10 mm rat sciatic nerve defect model, magnetically templated hydrogels demonstrated promising results with qualitatively increased remodeling and axon regeneration compared to non-templated controls. Significance. This simple and scalable technology has the flexibility to control tubular microstructure over long length scales, and thus the potential to meet the need for engineered scaffolds for tissue regeneration, including nerve guidance scaffolds.
Vascularization of large, diffusion-hindered biomaterial implants requires an understanding of how extracellular matrix (ECM) properties regulate angiogenesis. Sundry biomaterials assessed across ...many disparate angiogenesis assays have highlighted ECM determinants that influence this complex multicellular process. However, the abundance of material platforms, each with unique parameters to model endothelial cell (EC) sprouting presents additional challenges of interpretation and comparison between studies. In this work we directly compared the angiogenic potential of commonly utilized natural (collagen and fibrin) and synthetic dextran vinyl sulfone (DexVS) hydrogels in a multiplexed angiogenesis-on-a-chip platform. Modulating matrix density of collagen and fibrin hydrogels confirmed prior findings that increases in matrix density correspond to increased EC invasion as connected, multicellular sprouts, but with decreased invasion speeds. Angiogenesis in synthetic DexVS hydrogels, however, resulted in fewer multicellular sprouts. Characterizing hydrogel Young's modulus and permeability (a measure of matrix porosity), we identified matrix permeability to significantly correlate with EC invasion depth and sprout diameter. Although microporous collagen and fibrin hydrogels produced lumenized sprouts in vitro, they rapidly resorbed post-implantation into the murine epididymal fat pad. In contrast, DexVS hydrogels proved comparatively stable. To enhance angiogenesis within DexVS hydrogels, we incorporated sacrificial microgels to generate cell-scale pores throughout the hydrogel. Microporous DexVS hydrogels resulted in lumenized sprouts in vitro and enhanced cell invasion in vivo. Towards the design of vascularized biomaterials for long-term regenerative therapies, this work suggests that synthetic biomaterials offer improved size and shape control following implantation and that tuning matrix porosity may better support host angiogenesis.
Understanding how extracellular matrix properties govern angiogenesis will inform biomaterial design for engineering vascularized implantable grafts. Here, we utilized a multiplexed angiogenesis-on-a-chip platform to compare the angiogenic potential of natural (collagen and fibrin) and synthetic dextran vinyl sulfone (DexVS) hydrogels. Characterization of matrix properties and sprout morphometrics across these materials points to matrix porosity as a critical regulator of sprout invasion speed and diameter, supported by the observation that nanoporous DexVS hydrogels yielded endothelial cell sprouts that were not perfusable. To enhance angiogenesis into synthetic hydrogels, we incorporated sacrificial microgels to generate microporosity. We find that microporosity increased sprout diameter in vitro and cell invasion in vivo. This work establishes a composite materials approach to enhance the vascularization of synthetic hydrogels.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Small berries are rich in polyphenols whose first-pass metabolism may alter their ultimate physiological effects. The antioxidant capacity and polyphenol profile of three freeze-dried berries ...(blackberry, raspberry, Red Globe grape) were measured and their apparent permeability (Papp) and first-pass biotransformation were tracked with an ex vivo bioanalytical system everted gut sac (rat) + three detection methods: spectrophotometry, HPLC-ESI-QTOF-MS, differential pulse voltammetry (DPV). Total polyphenol (ratio 0.07-0.14-1.0) and molecular diversity (anthocyanins>flavan-3-ols), antioxidant capacity (DPPH, FRAP), anodic current
and Papp (efflux> uptake) were in the following order: blackberry > raspberry > Red Globe grape. Epicatechin, pelargonidin & cyanin (all), callistephin (raspberry/blackberry), catechin (grape), cyanidin glycosides (blackberry) and their derived metabolites quinic acid, epicatechin, cyanidin/malvidin glucosides, and chlorogenic/caffeic acids were fruit-specific and concentration-dependent. Time-trend DPV kinetic data revealed concurrent epithelial permeability & biotransformation processes. Regular permeability and high-biotransformation of berry polyphenols suggest fruit-specific health effects apparently at the intestinal level.
Mango "Ataulfo" peel is a rich source of polyphenols (PP), with antioxidant and anti-cancer properties; however, it is unknown whether such antiproliferative activity is related to PP's antioxidant ...activity. The content (HPLC-DAD), antioxidant (DPPH, FRAP, ORAC), and antiproliferative activities (MTT) of free (FP) and chemically-released PP from mango 'Ataulfo' peel after alkaline (AKP) and acid (AP) hydrolysis, were evaluated. AKP fraction was higher (µg/g DW) in gallic acid (GA; 23,816 ± 284) than AP (5610 ± 8) of FR (not detected) fractions. AKP fraction and GA showed the highest antioxidant activity (DPPH/FRAP/ORAC) and GA's antioxidant activity follows a single electron transfer (SET) mechanism. AKP and GA also showed the best antiproliferative activity against human colon adenocarcinoma cells (LS180; IC
(µg/mL) 138.2 ± 2.5 and 45.7 ± 5.2) and mouse connective cells (L929; 93.5 ± 7.7 and 65.3 ± 1.2); Cheminformatics confirmed the hydrophilic nature (LogP, 0.6) and a good absorption capacity (75%) for GA. Data suggests that GA's antiproliferative activity appears to be related to its antioxidant mechanism, although other mechanisms after its absorption could also be involved.
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Sweet potato (SP;
(L.) Lam) is an edible tuber native to America and the sixth most important food crop worldwide. China leads its production in a global market of USD 45 trillion. SP domesticated ...varieties differ in specific phenotypic/genotypic traits, yet all of them are rich in sugars, slow digestible/resistant starch, vitamins, minerals, bioactive proteins and lipids, carotenoids, polyphenols, ascorbic acid, alkaloids, coumarins, and saponins, in a genotype-dependent manner. Individually or synergistically, SP's phytochemicals help to prevent many illnesses, including certain types of cancers and cardiovascular disorders. These and other topics, including the production and market diversification of raw SP and its products, and SP's starch as a functional ingredient, are briefly discussed in this review.
Hibiscus sabdariffa and Camellia sinensis are traditionally consumed as beverages and are good sources of health-promoting phenolic compounds. The objective of this work was to use response surface ...methodology to develop an optimized functional beverage with high total phenolic content, antioxidant capacity, and acceptable for potential consumers. Optimum infusion conditions were 4.9 g of hibiscus calyces or C. sinensis leaves/100 ml of water at 26 ℃ for 291 min. These conditions yielded a total phenolic content of 14.80 ± 1.4 and 33.02 ± 0.34 mg gallic acid equivalents/100 ml for hibiscus and green tea, respectively. The optimized beverages were combined in a 7:3 (hibiscus:green tea, v/v) ratio; a consumer preference test showed that this combination had an acceptable taste according to untrained panelists. A chromatographic analysis showed that this formulation contained flavonoids, phenolic acids, and anthocyanins as its main components. Our data suggested that hibiscus and green tea phenolic compounds were efficiently extracted using near-ambient temperature water for prolonged times, contrary to routine methods (high temperature, short time). Our method also preserved antioxidant capacity, possibly by avoiding chemical changes/degradation due to high temperatures. This process can be used to produce organoleptically acceptable functional beverages that deliver a varied phenolic compound profile to the consumer.
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Avocado cv. ‘Hass’ paste is the main byproduct derived from industrial avocado processing, and contains various bioactive compounds (BCs). Consumption of these compounds from different sources has ...been associated with positive health effects, although studies of avocado byproducts remain minimal. Avocado paste was analyzed, regarding its physicochemical properties, proximate composition, main BCs, antioxidant capacity, in vitro digestion and in silico interactions of its three main phenolics with cholesterol. Avocado paste contained 14.2% of lipids and 13.8% of protein. Total phenolic compounds were 2.1 mg GAE/g dw, with a phenolic profile that contained phenolic acids (ferulic, protocatechuic and
p
-coumaric acids) as its main compounds. Carotenoids (mainly β-carotene), tocopherols (mainly α-tocopherol), fatty acids (mainly oleic acid) and other BCs were also identified and quantified. Release of its phenolic compounds and antioxidant capacity were highest in the gastric phase of an in vitro digestion. In silico analyses showed that ferulic acid had the strongest interaction with cholesterol, suggesting a possible mechanism to inhibit its intestinal absorption. According to its composition and characteristics, it is possible to suggest avocado paste may be used as an unconventional source of BCs, with possible effects on cholesterol digestion.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The hypoglycemic effect of functional phytochemicals has been evaluated in diabetic rodents but scarcely in its premorbid condition (prediabetes; PD). This study aimed to evaluate a mango (cv. ...Ataulfo) peel hydroethanolic (20:80) extract (MPE) for in vivo glycemic/lipidemic-normalizing effect and in vitro enzyme inhibitory (α-amylase/α-glucosidase) activity. The polyphenolic MPE (138 mg EAG.g−1, mainly gallic acid and mangiferin) with antioxidant capacity (DPPH• 34 mgTE.g−1) was fed to PD rats (induction: high-fat diet (60% energy) + single dose streptozotocin (35 mg·kg−1), 4 weeks). At the 8th week, fasting glycemia (FG), oral glucose tolerance test, and insulin sensitivity indexes (HOMA-IR, HOMA-β) > blood lipid-normalizing effect were documented as healthy controls > MPE > disease (PD) controls, which was possibly related to the extract’s concentration−response in vitro enzyme inhibitory activity (IC50 ≈ 0.085 mg·mL−1). MPE is a rich source of glucose-lowering phytochemicals for the primary prevention of type 2 diabetes.
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The fruit of Guamúchil is an excellent source of bioactive compounds for human health although their natural occurrence could be affected by the ripening process. The aim was to evaluate some ...physicochemical, chemical and antioxidant changes in guamúchil fruit during six ripening stages (I to VI). A defined trend (
p
≤ 0.003) was observed for color °Hue, 109 (light green) to 20 (dark red), anthocyanins (+571 %), soluble solids (+0.33
o
Brix), ash (+16 %), sucrose (−91 %), proanthocyanidins (63 %), ascorbic acid (−52 %) and hydrolysable PC (−21 %). Carotenoids were not detected and chlorogenic acid was the most abundant phenolic compound. Maximal availability of these bioactives per ripening stage (
p
≤ 0.03) was as follows: I (protein/ lipids/ sucrose/ proanthocyanidins/ hydrolysable phenolics), II (total sugars/ascorbic acid), III (total phenolics), IV (flavonoids/ chlorogenic acid) and VI (fructose/ glucose/ anthocyanins). Color change was explained by sucrose (β = 0.47) and anthocyanin (β = 0.20) contents (
p
< 0.001). Radical scavenging capacity (ORAC, DPPH and TEAC) strongly correlated with total PC (
r
= 0.49–0.65, p ≤ 0.001) but 89 % of ORAC’s associated variance was explained by anthocyanin + sucrose + ascorbic acid (
p
≤ 0.0001). Guamúchil fruit could be a more convenient source of specific bioactive compounds if harvested at different ripening stages.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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