Novel Therapeutic Nutrient Molecules

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (15 December 2020) | Viewed by 41983

Special Issue Editors


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Guest Editor
Department of Nutrition and Health Sciences, College of Education and Human Sciences, University of Nebraska at Lincoln, Lincoln, NE 68583, USA
Interests: maternal obesity; placental lipotoxicity; metabolic dysfunction-associated steatotic liver disease; apoptosis; liver cirrhosis; proline metabolism
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Co-Guest Editor
College of Allied Health Professions, University of Nebraska Medical Center, Omaha, NE 68198, USA
Interests: maternal–fetal nutrient interaction; the effects of omega-3 fatty acids against adverse pregnancy outcomes such as preterm
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue entitled “Novel Therapeutic Nutrient Molecules” will focus on the protective role of bioactive nutrient molecules as a therapeutic approach and against disease pathogenesis.

The identification of novel nutrient molecules for therapeutics or to prevent disease pathogenesis has been an attractive approach due to the ease of their translation to the general population. Recent advances in bioactive nutrient molecules protecting against human health outcomes has always been a growing field with new knowledge.

Our Special Issue will consider original articles, commentary and review articles that focus on the following potential topics (but not limited to these):

  • Investigations related to the nutrients of foods and their effects in improving human health.
  • Investigations related to novel nutrient compounds and their impact on the human gut microbiome and gut health.
  • Investigations related to the gut bioactive metabolites of nutrient molecules and their impact on human health.
  • The novel protective roles of vitamins and their metabolites against adverse health outcomes.

Dr. Sathish Kumar Natarajan
Dr. Corrine Hanson
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bioactive nutrient molecules
  • novel compounds in extracellular vesicles
  • gut microbial metabolites
  • novel gut metabolites of food

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Published Papers (8 papers)

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Research

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21 pages, 5837 KiB  
Article
Palmitoleate Protects against Zika Virus-Induced Placental Trophoblast Apoptosis
by Philma Glora Muthuraj, Aryamav Pattnaik, Prakash K. Sahoo, Md Torikul Islam, Asit K. Pattnaik, Siddappa N. Byrareddy, Corrine Hanson, Ann Anderson Berry, Stephen D. Kachman and Sathish Kumar Natarajan
Biomedicines 2021, 9(6), 643; https://doi.org/10.3390/biomedicines9060643 - 04 Jun 2021
Cited by 6 | Viewed by 2580
Abstract
Zika virus (ZIKV) infection in pregnancy is associated with the development of microcephaly, intrauterine growth restriction, and ocular damage in the fetus. ZIKV infection of the placenta plays a crucial role in the vertical transmission from the maternal circulation to the fetus. Our [...] Read more.
Zika virus (ZIKV) infection in pregnancy is associated with the development of microcephaly, intrauterine growth restriction, and ocular damage in the fetus. ZIKV infection of the placenta plays a crucial role in the vertical transmission from the maternal circulation to the fetus. Our previous study suggested that ZIKV induces endoplasmic reticulum (ER) stress and apoptosis of placental trophoblasts. Here, we showed that palmitoleate, an omega-7 monounsaturated fatty acid, prevents ZIKV-induced ER stress and apoptosis in placental trophoblasts. Human trophoblast cell lines (JEG-3 and JAR) and normal immortalized trophoblasts (HTR-8) were used. We observed that ZIKV infection of the trophoblasts resulted in apoptosis and treatment of palmitoleate to ZIKV-infected cells significantly prevented apoptosis. However, palmitate (saturated fatty acid) did not offer protection from ZIKV-induced ER stress and apoptosis. We also observed that the Zika viral RNA copies were decreased, and the cell viability improved in ZIKV-infected cells treated with palmitoleate as compared to the infected cells without palmitoleate treatment. Further, palmitoleate was shown to protect against ZIKV-induced upregulation of ER stress markers, C/EBP homologous protein and X-box binding protein-1 splicing in placental trophoblasts. In conclusion, our studies suggest that palmitoleate protects placental trophoblasts against ZIKV-induced ER stress and apoptosis. Full article
(This article belongs to the Special Issue Novel Therapeutic Nutrient Molecules)
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16 pages, 2748 KiB  
Article
Celastrol and Triptolide Suppress Stemness in Triple Negative Breast Cancer: Notch as a Therapeutic Target for Stem Cells
by Prabhu Ramamoorthy, Prasad Dandawate, Roy A. Jensen and Shrikant Anant
Biomedicines 2021, 9(5), 482; https://doi.org/10.3390/biomedicines9050482 - 28 Apr 2021
Cited by 20 | Viewed by 5346
Abstract
Triple negative breast cancer (TNBC) is observed in ~15% of breast cancers and results in poor survival and increased distant metastases. Within the tumor are present a small portion of cancer stem cells that drive tumorigenesis and metastasis. In this study, we aimed [...] Read more.
Triple negative breast cancer (TNBC) is observed in ~15% of breast cancers and results in poor survival and increased distant metastases. Within the tumor are present a small portion of cancer stem cells that drive tumorigenesis and metastasis. In this study, we aimed to elucidate whether the two natural compounds, celastrol and triptolide, inhibit stemness in TNBC. MDA-MB-231, BT20, and a patient-derived primary cells (PD-TNBC) were used in the study. Mammosphere assay was performed to assess the stemness. Both celastrol and triptolide treatment suppressed mammosphere formation. Furthermore, the compound suppressed expression of cancer stem cell marker proteins DCLK1, ALDH1, and CD133. Notch signaling plays a critical role in stem cells renewal. Both celastrol or triptolide reduced Notch -1 activation and expression of its downstream target proteins HES-1 and HEY-1. However, when NICD 1 was ectopically overexpressed in the cells, it partially rescued proliferation and mammosphere formation of the cells, supporting the role of notch signaling. Together, these data demonstrate that targeting stem cells and the notch signaling pathway may be an effective strategy for curtailing TNBC progression. Full article
(This article belongs to the Special Issue Novel Therapeutic Nutrient Molecules)
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14 pages, 3231 KiB  
Article
Dietary Vitamin B6 Deficiency Impairs Gut Microbiota and Host and Microbial Metabolites in Rats
by Shyamchand Mayengbam, Faye Chleilat and Raylene A. Reimer
Biomedicines 2020, 8(11), 469; https://doi.org/10.3390/biomedicines8110469 - 02 Nov 2020
Cited by 29 | Viewed by 5672
Abstract
Vitamin B6 plays a crucial role as a cofactor in various enzymatic reactions but bacteria-produced vitamin B6 is not sufficient to meet host requirements. Our objective was to assess the impact of diet-derived vitamin B6 on gut microbiota and host serum metabolomics. Sprague–Dawley [...] Read more.
Vitamin B6 plays a crucial role as a cofactor in various enzymatic reactions but bacteria-produced vitamin B6 is not sufficient to meet host requirements. Our objective was to assess the impact of diet-derived vitamin B6 on gut microbiota and host serum metabolomics. Sprague–Dawley rats (n = 47) were fed a control, low B6 (LB6) or high B6 (HB6) diet for six weeks. Serum and cecal samples were collected for biochemical, metabolomics and gut microbiota profiling. There was a significant sex effect for gut microbiota and several metabolic markers. Bodyweight and percent body fat were significantly reduced in LB6 compared to control and HB6 rats. Microbial beta-diversity differed significantly between LB6 and the control and HB6 rats in both sexes. Lachnospiraceae_NK4A136_group and Bacteroides were the primary taxa driving the difference between LB6 and control. There was a significant separation of cecal and serum metabolites of LB6 compared to control and HB6 rats. In the cecum, arginine biosynthesis was impaired, while vitamin B6 metabolism, lysine degradation and nicotinate and nicotinamide metabolism were impaired in serum metabolite profiles. Cecal propionate and butyrate were significantly reduced in LB6 rats irrespective of sex. Host vitamin B6 deficiency but not excess significantly alters gut microbial composition and its metabolites. Full article
(This article belongs to the Special Issue Novel Therapeutic Nutrient Molecules)
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10 pages, 542 KiB  
Article
Effect of Maternal Retinol Status at Time of Term Delivery on Retinol Placental Concentration, Intrauterine Transfer Rate, and Newborn Retinol Status
by Melissa Thoene, Haley Haskett, Jeremy Furtado, Maranda Thompson, Matthew Van Ormer, Corrine Hanson and Ann Anderson-Berry
Biomedicines 2020, 8(9), 321; https://doi.org/10.3390/biomedicines8090321 - 31 Aug 2020
Cited by 5 | Viewed by 1933
Abstract
Retinol (vitamin A) is essential, so the objective of this Institutional Review Board approved study is to evaluate retinol placental concentration, intrauterine transfer, and neonatal status at time of term delivery between cases of maternal retinol adequacy, insufficiency, and deficiency in a United [...] Read more.
Retinol (vitamin A) is essential, so the objective of this Institutional Review Board approved study is to evaluate retinol placental concentration, intrauterine transfer, and neonatal status at time of term delivery between cases of maternal retinol adequacy, insufficiency, and deficiency in a United States population. Birth information and biological samples were collected for mother–infant dyads (n = 260). Maternal and umbilical cord blood retinol concentrations (n = 260) were analyzed by HPLC and categorized: deficient (≤0.7 umol/L), insufficient (>0.7–1.05 umol/L), adequate (>1.05 umol/L). Intrauterine transfer rate was calculated: (umbilical cord blood retinol concentration/maternal retinol concentration) × 100. Non-parametric statistics used include Spearman’s correlations, Mann–Whitney U, and Kruskal–Wallis tests. p-values <0.05 were statistically significant. Only 51.2% of mothers were retinol adequate, with 38.4% insufficient, 10.4% deficient. Only 1.5% of infants were retinol adequate. Placental concentrations (n = 73) differed between adequate vs. deficient mothers (median 0.13 vs. 0.10 μg/g; p = 0.003). Umbilical cord blood concentrations were similar between deficient, insufficient, and adequate mothers (0.61 vs. 0.55 vs. 0.57 μmol/L; p = 0.35). Intrauterine transfer increased with maternal deficiency (103.4%) and insufficiency (61.2%) compared to adequacy (43.1%), p < 0.0001. Results indicate that intrauterine transfer rate is augmented in cases of maternal retinol inadequacy, leading to similar concentrations in umbilical cord blood at term delivery. Full article
(This article belongs to the Special Issue Novel Therapeutic Nutrient Molecules)
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19 pages, 2605 KiB  
Article
R-α-Lipoic Acid and 4-Phenylbutyric Acid Have Distinct Hypolipidemic Mechanisms in Hepatic Cells
by Bo He and Régis Moreau
Biomedicines 2020, 8(8), 289; https://doi.org/10.3390/biomedicines8080289 - 15 Aug 2020
Cited by 2 | Viewed by 3196
Abstract
The constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1) leads to the overproduction of apoB-containing triacylglycerol-rich lipoproteins in HepG2 cells. R-α-lipoic acid (LA) and 4-phenylbutyric acid (PBA) have hypolipidemic function but their mechanisms of action are not well understood. [...] Read more.
The constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1) leads to the overproduction of apoB-containing triacylglycerol-rich lipoproteins in HepG2 cells. R-α-lipoic acid (LA) and 4-phenylbutyric acid (PBA) have hypolipidemic function but their mechanisms of action are not well understood. Here, we reported that LA and PBA regulate hepatocellular lipid metabolism via distinct mechanisms. The use of SQ22536, an inhibitor of adenylyl cyclase, revealed cAMP’s involvement in the upregulation of CPT1A expression by LA but not by PBA. LA decreased the secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the culture media of hepatic cells and increased the abundance of LDL receptor (LDLR) in cellular extracts in part through transcriptional upregulation. Although PBA induced LDLR gene expression, it did not translate into more LDLR proteins. PBA regulated cellular lipid homeostasis through the induction of CPT1A and INSIG2 expression via an epigenetic mechanism involving the acetylation of histone H3, histone H4, and CBP-p300 at the CPT1A and INSIG2 promoters. Full article
(This article belongs to the Special Issue Novel Therapeutic Nutrient Molecules)
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14 pages, 957 KiB  
Article
Nutritional Supplementation Concurrent with Nutrition Education Accelerates the Wound Healing Process in Patients with Diabetic Foot Ulcers
by Raedeh Basiri, Maria T. Spicer, Cathy W. Levenson, Michael J. Ormsbee, Thomas Ledermann and Bahram H. Arjmandi
Biomedicines 2020, 8(8), 263; https://doi.org/10.3390/biomedicines8080263 - 03 Aug 2020
Cited by 22 | Viewed by 7757
Abstract
Trials on nutritional supplements for the treatment of diabetic foot ulcer (DFU) have only evaluated the effects of supplementation with specific nutrients. Additionally, nutrition education has not been a systematic part of these studies. The aim of this study was to evaluate the [...] Read more.
Trials on nutritional supplements for the treatment of diabetic foot ulcer (DFU) have only evaluated the effects of supplementation with specific nutrients. Additionally, nutrition education has not been a systematic part of these studies. The aim of this study was to evaluate the effects of a nutrient-dense formula combined with nutrition education on wound healing in DFU patients. Twenty-nine patients were randomly assigned to the treatment group (n = 15) receiving two servings of supplements daily plus nutrition education or control group (n = 14) that received the standard of care but no additional nutritional or educational intervention. Both groups were followed for a maximum of 12 weeks. Wound healing, as measured by planimetry, was examined at baseline and every four weeks until complete wound closure or up to 12 weeks. There were no significant differences between groups for BMI, age, duration of diabetes, wound age estimation, or wound area at baseline. The treatment group experienced a faster wound healing rate (6.43 mm2/week more reduction in the wound area) than the control group. The mean reduction in the wound area during the first four weeks of the study was almost 13-fold greater in the treatment group compared to the control group (18.0 mm2/week vs. 1.4 mm2/week, respectively). Our findings showed that nutrition supplementation plus nutrition education significantly accelerated wound healing in DFU patients compared to those who just received a standard-of-care regimen. Full article
(This article belongs to the Special Issue Novel Therapeutic Nutrient Molecules)
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19 pages, 759 KiB  
Review
Immunomodulatory Role of Urolithin A on Metabolic Diseases
by Ashley Mulcahy Toney, Darius Fox, Virginia Chaidez, Amanda E. Ramer-Tait and Soonkyu Chung
Biomedicines 2021, 9(2), 192; https://doi.org/10.3390/biomedicines9020192 - 15 Feb 2021
Cited by 42 | Viewed by 9670
Abstract
Urolithin A (UroA) is a gut metabolite produced from ellagic acid-containing foods such as pomegranates, berries, and walnuts. UroA is of growing interest due to its therapeutic potential for various metabolic diseases based on immunomodulatory properties. Recent advances in UroA research suggest that [...] Read more.
Urolithin A (UroA) is a gut metabolite produced from ellagic acid-containing foods such as pomegranates, berries, and walnuts. UroA is of growing interest due to its therapeutic potential for various metabolic diseases based on immunomodulatory properties. Recent advances in UroA research suggest that UroA administration attenuates inflammation in various tissues, including the brain, adipose, heart, and liver tissues, leading to the potential delay or prevention of the onset of Alzheimer’s disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. In this review, we focus on recent updates of the anti-inflammatory function of UroA and summarize the potential mechanisms by which UroA may help attenuate the onset of diseases in a tissue-specific manner. Therefore, this review aims to shed new insights into UroA as a potent anti-inflammatory molecule to prevent immunometabolic diseases, either by dietary intervention with ellagic acid-rich food or by UroA administration as a new pharmaceutical drug. Full article
(This article belongs to the Special Issue Novel Therapeutic Nutrient Molecules)
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19 pages, 887 KiB  
Review
Anti-NLRP3 Inflammasome Natural Compounds: An Update
by Baolong Liu and Jiujiu Yu
Biomedicines 2021, 9(2), 136; https://doi.org/10.3390/biomedicines9020136 - 01 Feb 2021
Cited by 13 | Viewed by 4999
Abstract
The nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome is a multimeric protein complex that recognizes various danger or stress signals from pathogens, the host, and the environment, leading to activation of caspase-1 and inducing inflammatory responses. [...] Read more.
The nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome is a multimeric protein complex that recognizes various danger or stress signals from pathogens, the host, and the environment, leading to activation of caspase-1 and inducing inflammatory responses. This pro-inflammatory protein complex plays critical roles in pathogenesis of a wide range of diseases including neurodegenerative diseases, autoinflammatory diseases, and metabolic disorders. Therefore, intensive efforts have been devoted to understanding its activation mechanisms and to searching for its specific inhibitors. Approximately forty natural compounds with anti-NLRP3 inflammasome properties have been identified. Here, we provide an update about new natural compounds that have been identified within the last three years to inhibit the NLRP3 inflammasome and offer an overview of the underlying molecular mechanisms of their anti-NLRP3 inflammasome activities. Full article
(This article belongs to the Special Issue Novel Therapeutic Nutrient Molecules)
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