Mesencephalic Astrocyte-Derived Neurotrophic Factor Is Upregulated with Therapeutic Fasting in Humans and Diet Fat Withdrawal in Obese Mice

Abstract Dietary restriction induces beneficial metabolic changes and prevents age-related deterioration. Mesencephalic astrocyte-derived neurotrophic factor (MANF) shows protective effects on cells in various models of degenerative diseases. Here we studied whether circulating concentrations of MANF are associated with fasting-induced positive effects. We quantified the levels of circulating MANF from 40 human subjects before and after therapeutic fasting. As measured by an enzyme-linked immunosorbent assay (ELISA), the mean concentration of plasma MANF increased after an average fasting of 15 days. Plasma MANF levels correlated inversely with adiponectin, a hormone that regulates metabolism, thus suggesting that MANF levels are related to metabolic homeostasis. To study the effects of dietary intervention on MANF concentrations in mice, we developed an ELISA for mouse MANF and verified its specificity using MANF knock-out (KO) tissue. A switch from high-fat to normal diet increased MANF levels and downregulated the expression of unfolded protein response (UPR) genes in the liver, indicating decreased endoplasmic reticulum (ER) stress. Liver MANF and serum adiponectin concentrations correlated inversely in mice. Our findings demonstrate that MANF expression and secretion increases with dietary intervention. The MANF correlation to adiponectin and its possible involvement in metabolic regulation and overall health warrants further studies.

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Associations Between Serum Lutein and Human Gut Microbiota (P02-004-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz029.p02-004-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Andrew Dinsmoor ◽

Sharon Thompson ◽

Caitlyn Edwards ◽

Nicholas Burd ◽

Naiman Khan ◽

...

Keyword(s):

Dietary Intervention ◽

Adult Population ◽

Venous Blood ◽

Age Related Macular Degeneration ◽

Leafy Vegetables ◽

Whole Body ◽

Rrna Gene ◽

Protective Effects ◽

Food Record ◽

Age Related

Abstract Objectives Lutein is a carotenoid found in green leafy vegetables, avocados, and eggs, and is purported to have protective effects against age-related macular degeneration (AMD) as well as benefits for visual and cognitive health. Recent studies have indicated significant variation in serum lutein among individuals and that gastrointestinal (GI) microbial profile may potentially contribute to lutein status. However, the extent to which the GI microbiota contribute to lutein is unclear. The current study aimed to determine GI microbial predictors of serum lutein in a healthy young adult population. Methods Among adults ages 25–45 years (N = 105), venous blood was collected following a 10-hour fast. Serum lutein was determined using HPLC. Fecal DNA was extracted and the V4 region of the 16S rRNA gene was amplified. Amplicon sequence variants were assigned using the GreenGenes 13-8 database and DADA2, followed by analysis in QIIME2 and LDA Effect Size (LEfSe). Participants underwent DXA scan for whole body % fat (%Fat) and completed a 7-day food record to assess lutein consumption. Demographic information on participant's age and sex was also assessed and included in the statistical models. Results Four genera (Dialister, Ruminococcus, Gemmiger, and Phascolarctobacterium) and two species (Bacteroides eggerthii, Ruminococcus torques) were different between individuals in the highest and lowest quartiles of serum lutein. The genera Ruminococcus (Rho = −0.24, P = 0.02) and Phascolarctobacterium (Rho = −0.21, P = 0.03) and species R. torques (Rho = −0.35, P < 0.001) were inversely related to serum lutein. Linear regression modelling, adjusted for age, sex, %Fat, and dietary lutein, revealed that R. torques was the only significant predictor of serum lutein concentrations, accounting for 8.4% of the variance. Conclusions Our results reveal that individuals with lower serum lutein concentrations have a higher relative abundance of R. torques than those with higher lutein concentrations. As R. torques has been shown to be elevated in those with AMD, it is possible the relationship between this microbe and lutein is evident earlier in adulthood. However, further dietary intervention trials are warranted to clarify the relations among R. torques and serum lutein concentrations. Funding Sources This work was supported by funds provided by the Department of Kinesiology and Community Health at the University of Illinois and the USDA National Institute of Food and Agriculture, Hatch Project 1009249. Partial support was also provided by the Hass Avocado Board.

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Effects of a Newly Developed Enzyme-Assisted Extraction Method on the Biological Activities of Fucoidans in Ocular Cells

Marine Drugs ◽

10.3390/md18060282 ◽

2020 ◽

Vol 18 (6) ◽

pp. 282 ◽

Cited By ~ 4

Author(s):

Philipp Dörschmann ◽

Maria Dalgaard Mikkelsen ◽

Thuan Nguyen Thi ◽

Johann Roider ◽

Anne S. Meyer ◽

...

Keyword(s):

High Performance ◽

Biological Activities ◽

Alginate Lyase ◽

Extraction Methods ◽

Exchange Chromatography ◽

Age Related Macular Degeneration ◽

Saccharina Latissima ◽

Enzyme Linked Immunosorbent Assay ◽

Protective Effects ◽

Age Related

Fucoidans from brown seaweeds are promising substances as potential drugs against age-related macular degeneration (AMD). The heterogeneity of fucoidans requires intensive research in order to find suitable species and extraction methods. Ten different fucoidan samples extracted enzymatically from Laminaria digitata (LD), Saccharina latissima (SL) and Fucus distichus subsp. evanescens (FE) were tested for toxicity, oxidative stress protection and VEGF (vascular endothelial growth factor) inhibition. For this study crude fucoidans were extracted from seaweeds using different enzymes and SL fucoidans were further separated into three fractions (SL_F1-F3) by ion-exchange chromatography (IEX). Fucoidan composition was analyzed by high performance anion exchange chromatography (HPAEC) after acid hydrolysis. The crude extracts contained alginate, while two of the fractionated SL fucoidans SL_F2 and SL_F3 were highly pure. Cell viability was assessed with an 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay in OMM-1 and ARPE-19. Protective effects were investigated after 24 h of stress insult in OMM-1 and ARPE-19. Secreted VEGF was analyzed via ELISA (enzyme-linked immunosorbent assay) in ARPE-19 cells. Fucoidans showed no toxic effects. In OMM-1 SL_F2 and several FE fucoidans were protective. LD_SiAT2 (Cellic®CTec2 + Sigma-Aldrich alginate lyase), FE_SiAT3 (Cellic® CTec3 + Sigma-Aldrich alginate lyase), SL_F2 and SL_F3 inhibited VEGF with the latter two as the most effective. We could show that enzyme treated fucoidans in general and the fractionated SL fucoidans SL_F2 and SL_F3 are very promising for beneficial AMD relevant biological activities.

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Impact of Silibinin A on Bioenergetics in PC12APPsw Cells and Mitochondrial Membrane Properties in Murine Brain Mitochondria

Antioxidants ◽

10.3390/antiox10101520 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1520

Author(s):

Carsten Esselun ◽

Bastian Bruns ◽

Stephanie Hagl ◽

Rekha Grewal ◽

Gunter P. Eckert

Keyword(s):

Mitochondrial Dysfunction ◽

Mitochondrial Function ◽

Mitochondrial Membrane ◽

Brain Mitochondria ◽

Membrane Properties ◽

Protective Effects ◽

Positive Effects ◽

Atp Levels ◽

Age Related ◽

Murine Brain

Introduction: Age-related multifactorial diseases, such as the neurodegenerative Alzheimer’s disease (AD), still remain a challenge to today’s society. One mechanism associated with AD and aging in general is mitochondrial dysfunction (MD). Increasing MD is suggested to trigger other pathological processes commonly associated with neurodegenerative diseases. Silibinin A (SIL) is the main bioactive compound of the Silymarin extract from the Mediterranean plant Silybum marianum (L.) (GAERTN/Compositae). It is readily available as a herbal drug and well established in the treatment of liver diseases as a potent radical scavenger reducing lipid peroxidation and stabilize membrane properties. Recent data suggest that SIL might also act on neurological changes related to MD. Methods: PC12APPsw cells produce low levels of human Aβ and thus act as a cellular model of early AD showing changed mitochondrial function. We investigated whether SIL could affect mitochondrial function by measuring ATP, MMP, as well as respiration, mitochondrial mass, cellular ROS and lactate/pyruvate concentrations. Furthermore, we investigated its effects on the mitochondrial membrane parameters of swelling and fluidity in mitochondria isolated from the brains of mice. Results: In PC12APPsw cells, SIL exhibits strong protective effects by rescuing MMP and ATP levels from SNP-induced mitochondrial damage and improving basal ATP levels. However, SIL did not affect mitochondrial respiration and mitochondrial content. SIL significantly reduced cellular ROS and pyruvate concentrations. Incubation of murine brain mitochondria with SIL significantly reduces Ca2+ induced swelling and improves membrane fluidity. Conclusions: Although OXPHOS activity was unaffected at this early stage of a developing mitochondrial dysfunction, SIL showed protective effects on MMP, ATP- after SNP-insult and ROS-levels in APPsw-transfected PC12 cells. Results from experiments with isolated mitochondria imply that positive effects possibly result from an interaction of SIL with mitochondrial membranes and/or its antioxidant activity. Thus, SIL might be a promising compound to improve cellular health when changes to mitochondrial function occur.

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The Effect of Anthocyanins on Microcirculation and Retrobulbar Blood Flow in Ocular Pathology

Ophthalmology in Russia ◽

10.18008/1816-5095-2019-3-360-365 ◽

2019 ◽

Vol 16 (3) ◽

pp. 360-365

Author(s):

T. N. Kiseleva ◽

T. V. Sudovskaya ◽

M. S. Zaitsev ◽

K. V. Lugovkina

Keyword(s):

Blood Flow ◽

Metabolic Regulation ◽

Vascular Reactivity ◽

Open Angle Glaucoma ◽

Visual Fields ◽

Age Related Macular Degeneration ◽

Positive Effects ◽

Age Related ◽

Retrobulbar Blood Flow ◽

Functional Indices

The literature review presents information on positive effects of anthocyanins on functional indices of cardiovascular system, vascular reactivity of main arteries, microcirculation and retrobulbar blood flow. The positive effect of anthocyanins on the reactivity of main arteries was detected using non-invasive ultrasound method for assessment of flow-mediated dilation andendothelial function. Numerous randomised-controlled trials showed the effectiveness of the long-term supplementation with anthocyanins (during 6–24 months) in correction of microcirculation impairment and functional indices of visual system. The increase of plasma endothelin-1 (ET-1) level and the pathological vascular reactivity have been noted in ocular ischemic diseases such as diabetic retinopathy, occlusion of retinal veins and arteries. We registered the normalization of the plasma ET-1 level, significant improvement of blood flow in neuroretinal rim area and peripapillary area of retina without changes in mean indices of intraocular pressure and ocular perfusion pressure in patients with open-angle glaucoma after anthocyanins administration. There was no progression of visual fields defects. The resulting effect of anthocyanins supplementation consists of metabolic regulation of blood flow and flow-dependent vasodilatation due to the influence on vascular endothelium.Anthocyanins also increase the expression of endothelial nitric oxide (NO) synthase, an enzyme that generates powerful endogenous vasodilator NO. Anthocyanins regulate a number of complex immune and inflammatory signaling pathways involved in maintaining vascular functional activity. Positive dynamic of blood flow velocities and normalization of resistance indices in ocular vessels were detected in patients with dry age-related macular degeneration after 2 months anthocyanins supplementation. That indicates the improvement of ocular blood flow circulation and favorable prognosis for retinal dystrophies. The instrumental examination of blood flow in different vascular systems including microcirculation and main arteries are very useful for assessment of the effectiveness of anthocyanin supplementation.

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Oolonghomobisflavans from Camellia sinensis increase Caenorhabditis elegans lifespan and healthspan

GeroScience ◽

10.1007/s11357-021-00462-7 ◽

2021 ◽

Author(s):

Chatrawee Duangjan ◽

Sean P. Curran

Keyword(s):

Caenorhabditis Elegans ◽

Camellia Sinensis ◽

Healthy Aging ◽

Health Benefits ◽

Normal Diet ◽

Bioactive Molecules ◽

Protective Effects ◽

Oolong Tea ◽

Age Related ◽

Antioxidant Agents

AbstractTea polyphenols are widely considered as excellent antioxidant agents which can contribute to human health and longevity. However, the identification of the active biomolecules in complex tea extracts that promote health and longevity are not fully known. Here we used the nematode Caenorhabditis elegans to analyze the health benefits and longevity effects of Camellia sinensis oolong tea extracts (QFT, NFT, and CFT) and oolonghomobisflavan A and oolonghomobisflavan B, which are present in oolong tea extracts. Our results showed that oolong tea extracts and oolonghomobisflavans prolong lifespan and improved healthspan by curtailing the age-related decline in muscle activity and the accumulation of age pigment (lipofuscin). We found that the lifespan and healthspan promoting effects of oolong tea extracts and oolonghomobisflavans were positively correlated with the stress resistance via DAF-16/FOXO transcription factor. Furthermore, oolong tea extracts and oolonghomobisflavans displayed protective effects against Aβ- and polyQ-induced neuro/proteotoxicity. Overall, our study provides new evidence to support the health benefits of oolong tea and importantly identify oolonghomobisflavans as potent bioactive molecules that promote health when supplemented with a normal diet. As such, oolonghomobisflavans represent a valuable new class of compounds that promote healthy aging.

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Apitherapy for Age-Related Skeletal Muscle Dysfunction (Sarcopenia): A Review on the Effects of Royal Jelly, Propolis, and Bee Pollen

Foods ◽

10.3390/foods9101362 ◽

2020 ◽

Vol 9 (10) ◽

pp. 1362 ◽

Cited By ~ 3

Author(s):

Amira Mohammed Ali ◽

Hiroshi Kunugi

Keyword(s):

Skeletal Muscle ◽

Metabolic Regulation ◽

Royal Jelly ◽

Experimental Models ◽

Laboratory Animals ◽

Multiple Chronic Conditions ◽

Bee Pollen ◽

Positive Effects ◽

Age Related ◽

Catabolic Genes

The global pandemic of sarcopenia, skeletal muscle loss and weakness, which prevails in up to 50% of older adults is increasing worldwide due to the expansion of aging populations. It is now striking young and midlife adults as well because of sedentary lifestyle and increased intake of unhealthy food (e.g., western diet). The lockdown measures and economic turndown associated with the current outbreak of Coronavirus Disease 2019 (COVID-19) are likely to increase the prevalence of sarcopenia by promoting sedentarism and unhealthy patterns of eating. Sarcopenia has multiple detrimental effects including falls, hospitalization, disability, and institutionalization. Although a few pharmacological agents (e.g., bimagrumab, sarconeos, and exercise mimetics) are being explored in different stages of trials, not a single drug has been approved for sarcopenia treatment. Hence, research has focused on testing the effect of nutraceuticals, such as bee products, as safe treatments to prevent and/or treat sarcopenia. Royal jelly, propolis, and bee pollen are common bee products that are rich in highly potent antioxidants such as flavonoids, phenols, and amino acids. These products, in order, stimulate larval development into queen bees, promote defenses of the bee hive against microbial and environmental threats, and increase royal jelly production by nurse bees. Thanks to their versatile pharmacological activities (e.g., anti-aging, anti-inflammatory, anticarcinogenic, antimicrobial, etc.), these products have been used to treat multiple chronic conditions that predispose to muscle wasting such as hypertension, diabetes mellitus, cardiovascular disorder, and cancer, to name a few. They were also used in some evolving studies to treat sarcopenia in laboratory animals and, to a limited degree, in humans. However, a collective understanding of the effect and mechanism of action of these products in skeletal muscle is not well-developed. Therefore, this review examines the literature for possible effects of royal jelly, bee pollen, and propolis on skeletal muscle in aged experimental models, muscle cell cultures, and humans. Collectively, data from reviewed studies denote varying levels of positive effects of bee products on muscle mass, strength, and function. The likely underlying mechanisms include amelioration of inflammation and oxidative damages, promotion of metabolic regulation, enhancement of satellite stem cell responsiveness, improvement of muscular blood supply, inhibition of catabolic genes, and promotion of peripheral neuronal regeneration. This review offers suggestions for other mechanisms to be explored and provides guidance for future trials investigating the effects of bee products among people with sarcopenia.

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The effects of probiotics on colon cancer development

Nutrition Research Reviews ◽

10.1079/nrr200484 ◽

2004 ◽

Vol 17 (2) ◽

pp. 277-284 ◽

Cited By ~ 52

Author(s):

Joseph Rafter

Keyword(s):

Colon Cancer ◽

Lactic Acid ◽

Lactic Acid Bacteria ◽

Dietary Intervention ◽

Human Subjects ◽

Indirect Evidence ◽

Present Review ◽

Protective Effects ◽

Anti Cancer

While several effects beneficial to health have been attributed to the probiotic lactic acid bacteria, perhaps the most interesting and controversial remains that of anti-cancer activity. The vast majority of studies in this area deal with protective effects against colon cancer. There is no direct experimental evidence for cancer suppression in human subjects as a result of the consumption of probiotic cultures in fermented or unfermented dairy products. However, there is a wealth of indirect evidence, based largely on laboratory studies. Reports in the literature, regarding the anti-cancer effects of lactic acid bacteria, fall into the following categories:in vitrostudies, animal studies, epidemiological studies and human dietary intervention studies. Examples of these reports will be given in the present review. The mechanisms by which probiotic bacteria may inhibit colon cancer are still poorly understood. However, several potential mechanisms are being discussed in the literature and these will also be addressed in the present review.

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Protective effects of soy-isoflavones in cardiovascular disease

Hämostaseologie ◽

10.1055/s-0037-1616927 ◽

2008 ◽

Vol 28 (01/02) ◽

pp. 85-88 ◽

Cited By ~ 16

Author(s):

D. Fuchs ◽

H. Daniel ◽

U. Wenzel

Keyword(s):

Cardiovascular Disease ◽

Endothelial Cells ◽

Molecular Mechanisms ◽

Dietary Intervention ◽

Mononuclear Cells ◽

Oxidized Ldl ◽

Proteome Analysis ◽

Soy Isoflavones ◽

Protective Effects ◽

Estrogen Production

SummaryEpidemiological studies indicate that the consumption of soy-containing food may prevent or slow-down the development of cardiovascular disease. In endothelial cells application of a soy extract or a combination of the most abundant soy isoflavones genistein and daidzein both inhibited apoptosis, a driving force in atherosclerosis development, when applied in combination with oxidized LDL or homocysteine. Proteome analysis revealed that the stressorinduced alteration of protein expression profile was reversed by the soy extract or the genistein/daidzein mixture. Only few protein entities that could be functionally linked to mitochondrial dysfunction were regulated in common by both application forms of isoflavones. A dietary intervention with isoflavone-enriched soy extract in postmenopausal women, who generally show strongly increased cardiovascular risk due to diminished estrogen production, led to significant alterations in the steady state levels of proteins from mononuclear blood cells. The proteins identified by proteome analysis revealed that soy isoflavones may increase the anti-inflammatory response in blood mononuclear cells thereby contributing to the atherosclerosispreventive activities of a soy-rich diet. Conclusion: By proteome analysis protein targets were identified in vitro in endothelial cells that respond to soy isoflavones and that may decipher molecular mechanisms through which soy products exert their protective effects in the vasculature.

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The Impact of Ultraviolet Radiation on Barrier Function in Human Skin: Molecular Mechanisms and Topical Therapeutics

Current Medicinal Chemistry ◽

10.2174/0929867324666171106164916 ◽

2019 ◽

Vol 25 (40) ◽

pp. 5503-5511 ◽

Cited By ~ 5

Author(s):

Abdulaziz Alhasaniah ◽

Michael J. Sherratt ◽

Catherine A. O'Neill

Keyword(s):

Ultraviolet Radiation ◽

Barrier Function ◽

Molecular Mechanisms ◽

Transepidermal Water Loss ◽

Protective Effects ◽

Barrier Dysfunction ◽

Epidermal Barrier ◽

Positive Effects ◽

Terrestrial Mammals ◽

The Impact

A competent epidermal barrier is crucial for terrestrial mammals. This barrier must keep in water and prevent entry of noxious stimuli. Most importantly, the epidermis must also be a barrier to ultraviolet radiation (UVR) from the sunlight. Currently, the effects of ultraviolet radiation on epidermal barrier function are poorly understood. However, studies in mice and more limited work in humans suggest that the epidermal barrier becomes more permeable, as measured by increased transepidermal water loss, in response UVR, at doses sufficiently high to induce erythema. The mechanisms may include disturbance in the organisation of lipids in the stratum corneum (the outermost layer of the epidermis) and reduction in tight junction function in the granular layer (the first living layer of the skin). By contrast, suberythemal doses of UVR appear to have positive effects on epidermal barrier function. Topical sunscreens have direct and indirect protective effects on the barrier through their ability to block UV and also due to their moisturising or occlusive effects, which trap water in the skin, respectively. Some topical agents such as specific botanical extracts have been shown to prevent the loss of water associated with high doses of UVR. In this review, we discuss the current literature and suggest that the biology of UVR-induced barrier dysfunction, and the use of topical products to protect the barrier, are areas worthy of further investigation.

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Enhanced Bilosomal Properties Resulted in Optimum Pharmacological Effects by Increased Acidification Pathways

Pharmaceutics ◽

10.3390/pharmaceutics13081184 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1184

Author(s):

Armin Mooranian ◽

Thomas Foster ◽

Corina M Ionescu ◽

Daniel Walker ◽

Melissa Jones ◽

...

Keyword(s):

Bile Acids ◽

Biological Effects ◽

Cellular Respiration ◽

Full Potential ◽

Protective Effects ◽

Pharmacological Effects ◽

Β Cells ◽

Positive Effects ◽

Wide Range ◽

Anti Inflammatory

Introduction: Recent studies in our laboratory have shown that some bile acids, such as chenodeoxycholic acid (CDCA), can exert cellular protective effects when encapsulated with viable β-cells via anti-inflammatory and anti-oxidative stress mechanisms. However, to explore their full potential, formulating such bile acids (that are intrinsically lipophilic) can be challenging, particularly if larger doses are required for optimal pharmacological effects. One promising approach is the development of nano gels. Accordingly, this study aimed to examine biological effects of various concentrations of CDCA using various solubilising nano gel systems on encapsulated β-cells. Methods: Using our established cellular encapsulation system, the Ionic Gelation Vibrational Jet Flow technology, a wide range of CDCA β-cell capsules were produced and examined for morphological, biological, and inflammatory profiles. Results and Conclusion: Capsules’ morphology and topographic characteristics remained similar, regardless of CDCA or nano gel concentrations. The best pharmacological, anti-inflammatory, and cellular respiration, metabolism, and energy production effects were observed at high CDCA and nano gel concentrations, suggesting dose-dependent cellular protective and positive effects of CDCA when incorporated with high loading nano gel.

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