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Vitamins, Nutritional Supplements, Antioxidant Therapy, and Modulators of Inflammation as Therapeutic Interventions

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutritional Immunology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 17126

Special Issue Editors


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Guest Editor
1.Department of Biological Adaptation and Aging, B2A (CNRS UMR 8256-INSERM ERL U1164-UPMC P6), Sorbonne University, 75005 Paris, France
2. DAHFMO Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161 Rome, Italy
Interests: cancer biology; cell biology; tissue engineering; cell culture; stem cell biology; skeletal muscle physiology

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Guest Editor
Unit of Biology and Genetics, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Piazza Lauro de Bosis 15, 00135 Rome, Italy
Interests: oxidative stress; molecular biology; gene expression; stem cell biology; transcriptomics

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Guest Editor
Laboratory of Clinical Investigation: Experimental Surgery (LIM/26), Clinics’ Hospital of Medical School, University of Sao Paulo, São Paulo 01246-903, SP, Brazil
Interests: nutrition; performance; metabolism; obesity

Special Issue Information

Dear Colleagues,

Vitamins are essential micronutrients, with a well-established role in inflammation and metabolism. In some cases, the beneficial effects of vitamins stem from their antioxidant capacity and can be substituted by antioxidant pharmacological treatments. Additionally, numerous natural compounds have these properties and are now explored as immune modulators. Indeed, targeting oxidative stress is proposed for the treatment or management of major pathological disease states, from diabetes to obesity and from hypertension to cachexia. The most innovative approaches in medicine, such as multimodal interventions and tailored medicine, currently include nutritional supplementation to buffer the redox status of the body or to naturally trigger beneficial signaling pathways to control inflammation and metabolic alterations. Nonetheless, limitations still exist and further knowledge on the molecular mechanisms underlying the effects of nutritional and antioxidant supplementation is needed to expand the margins of intervention.

Dr. Dario Coletti
Dr. Daniela Caporossi
Prof. Dr. Antonio Hebert Lancha Jr.
Guest Editors

Manuscript Submission Information

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Keywords

  • oxidative stress
  • inflammation
  • anti-inflammatory treatments
  • polyunsaturated fatty acids
  • branched chain aminoacids
  • personalized medicine
  • multimodal interventions

Published Papers (8 papers)

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13 pages, 2006 KiB  
Article
Hepatoprotection of a Standardized Extract of Cultured Lentinula edodes Mycelia against Liver Injury Induced by Ischemia-Reperfusion and Partial Hepatectomy
by Richi Nakatake, Tetsuya Okuyama, Morihiko Ishizaki, Hidesuke Yanagida, Hiroaki Kitade, Katsuhiko Yoshizawa, Mikio Nishizawa and Mitsugu Sekimoto
Nutrients 2024, 16(2), 256; https://doi.org/10.3390/nu16020256 - 14 Jan 2024
Viewed by 1075
Abstract
A standardized extract of cultured Lentinula edodes mycelia (ECLM, AHCC®) has been shown to have beneficial effects on organ metabolism. ECLM has been indicated to have liver protective properties by suppressing inflammatory responses. The pathogenesis of hepatic ischemia-reperfusion injury is thought [...] Read more.
A standardized extract of cultured Lentinula edodes mycelia (ECLM, AHCC®) has been shown to have beneficial effects on organ metabolism. ECLM has been indicated to have liver protective properties by suppressing inflammatory responses. The pathogenesis of hepatic ischemia-reperfusion injury is thought to involve the induction of inflammatory mediators. However, whether ECLM affects inflammatory mediators caused by warm hepatic ischemia-reperfusion injury and partial hepatectomy (HIRI+PH) has not been clarified. In this study, we evaluated the protective effects of ECLM against liver damage caused by HIRI+PH. Rats were fed a normal diet (HIRI+PH) or a normal diet with 2% ECLM (HIRI+PH and ECLM) for ten days, then the liver and duodenal ligament were clamped and subjected to 15 min of hepatic ischemia. After 70% hepatectomy, the inflow occlusion was released, and liver and blood samples were collected at 3, 6, and 24 h. The effect of ECLM on mortality induced by 30 min of ischemia and hepatectomy was evaluated. The results showed that ECLM attenuated pathological liver damage, including apoptosis, in the rats treated with HIRI+PH, and decreased serum aminotransferase activity; ECLM decreased mRNA levels of the inflammation-related genes inducible nitric oxide synthase and C-X-C motif chemokine ligand 1, and increased mRNA levels of interleukin 10, an anti-inflammatory cytokine; ECLM increased hepatocyte growth factor mRNA levels and Ki-67 labeled nuclei in the liver at 24 h; ECLM significantly reduced HIRI+PH-induced mortality. In conclusion, ECLM may prevent HIRI+PH-induced liver injury in part by suppressing various inflammatory responses and promoting liver regeneration. Full article
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15 pages, 2766 KiB  
Article
Vitamin D Attenuates Ulcerative Colitis by Inhibiting ACSL4-Mediated Ferroptosis
by Shuo Gao, Can Sun and Juan Kong
Nutrients 2023, 15(22), 4845; https://doi.org/10.3390/nu15224845 - 20 Nov 2023
Viewed by 1400
Abstract
Background: With environmental and lifestyle changes, recent epidemiological studies have shown that the prevalence of Ulcerative Colitis (UC) is on the rise, while treatment options are limited. There is an urgent need to explore the underlying mechanisms of vitamin D (VD) as an [...] Read more.
Background: With environmental and lifestyle changes, recent epidemiological studies have shown that the prevalence of Ulcerative Colitis (UC) is on the rise, while treatment options are limited. There is an urgent need to explore the underlying mechanisms of vitamin D (VD) as an effective treatment. Methods: Dextran sulfate sodium-induced mice and lipopolysaccharide-induced HCT116 cells were used to establish the classic UC models in vivo and in vitro, respectively. Typical symbols of inflammation (IL-6, COX-2), oxidative stress (MDA, MPO, GSH), and ferroptosis (ACSL4, GPX4, SLC7A11, and Iron) were analyzed by Western blot, Immunohistochemistry, RT-PCR, and relative assay kits. The inflammation factors and oxidative stress injury of cells transfected with ACSL4+/+ plasmids were tested by Western blot, MDA, and MPO methods. Results: Vitamin D attenuated the levels of COX-2, IL-6, Iron, MDA, and MPO and improved SOD1 and GSH contents in DSS + VD and LPS + VD groups, compared with model groups. Ferrostatin-1 (Fer-1) could relieve the levels of COX-2, IL-6, Iron, MDA, and MPO while increasing the contents of SOD1 and GSH in DSS + Fer-1 and LPS + Fer-1 compared to model groups. VD downregulated the expression of ACSL4 and upregulated GPX4 in tissues and cells. After transfected with ACSL4+/+ plasmids, we found VD’s role of downregulating inflammation and oxidative stress was relieved. Conclusions: Vitamin D can relieve UC by inhibiting ferroptosis both in mice and in cells through the negative regulation of ACSL4, providing new insight into the therapeutic function of VD on UC. Full article
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17 pages, 942 KiB  
Article
Nrf2-Mediated Pathway Activated by Prunus spinosa L. (Rosaceae) Fruit Extract: Bioinformatics Analyses and Experimental Validation
by Mariastella Colomba, Serena Benedetti, Daniele Fraternale, Andrea Guidarelli, Sofia Coppari, Valerio Freschi, Rita Crinelli, George E. N. Kass, Andrea Gorassini, Giancarlo Verardo, Carla Roselli, Maria Assunta Meli, Barbara Di Giacomo and Maria Cristina Albertini
Nutrients 2023, 15(9), 2132; https://doi.org/10.3390/nu15092132 - 28 Apr 2023
Cited by 2 | Viewed by 1162
Abstract
In our previous studies, Prunus spinosa fruit (PSF) ethanol extract was showed to exert antioxidant, antimicrobial, anti-inflammatory and wound healing activities. In the present study, an integrated bioinformatics analysis combined with experimental validation was carried out to investigate the biological mechanism(s) that are [...] Read more.
In our previous studies, Prunus spinosa fruit (PSF) ethanol extract was showed to exert antioxidant, antimicrobial, anti-inflammatory and wound healing activities. In the present study, an integrated bioinformatics analysis combined with experimental validation was carried out to investigate the biological mechanism(s) that are responsible for the reported PSF beneficial effects as an antioxidant during a pro-inflammatory TLR4 insult. Bioinformatics analysis using miRNet 2.0 was carried out to address which biological process(es) the extract could be involved in. In addition, Chemprop was employed to identify the key targets of nuclear receptor (NR) signaling and stress response (SR) pathways potentially modulated. The miRNet analysis suggested that the PSF extract mostly activates the biological process of cellular senescence. The Chemprop analysis predicted three possible targets for nine phytochemicals found in the extract: (i) ARE signaling, (ii) mitochondrial membrane potential (MMP) and (iii) p53 SR pathways. The PSF extract antioxidant effect was also experimentally validated in vitro using the human monocyte U937 cell line. Our findings showed that Nrf2 is modulated by the extract with a consequent reduction of the oxidative stress level. This was confirmed by a strong decrease in the amount of reactive oxygen species (ROS) observed in the PSF-treated cells subjected to lipopolysaccharide (LPS) (6 h treatment, 1 µg/mL). No visible effects were observed on p53 and MMP modulation. Full article
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13 pages, 4674 KiB  
Article
Vitamin A Ameliorated Irinotecan-Induced Diarrhea in a Piglet Model Involving Enteric Glia Modulation and Immune Cells Infiltration
by Meng Li, Yonggang Huang, Huimin Jin, Daixiu Yuan, Ke Huang, Jing Wang, Bie Tan and Yulong Yin
Nutrients 2022, 14(23), 5120; https://doi.org/10.3390/nu14235120 - 02 Dec 2022
Cited by 2 | Viewed by 1955
Abstract
Vitamin A (VA) and its metabolite, retinoic acid (RA), play important roles in modulating intestinal mucosal immunity, yet little is known about their regulatory effects on enteric nervous system function. The study aims to explore the protective effects of dietary VA on diarrhea [...] Read more.
Vitamin A (VA) and its metabolite, retinoic acid (RA), play important roles in modulating intestinal mucosal immunity, yet little is known about their regulatory effects on enteric nervous system function. The study aims to explore the protective effects of dietary VA on diarrhea in a piglet model involving enteric glia and immune cell modulation. Twenty-eight weaned piglets were fed either the basal or VA (basal diet supplemented with 18,000 IU/kg VA) diet and with or without irinotecan (CPT-11) injection. CPT-11 induced increased diarrhea incidence, immune infiltration, and reactive enteric gliosis. A diet supplemented with 18,000 IU/kg VA ameliorated the adverse effects of CPT-11 on the gut barrier. VA reduced diarrhea incidence and attenuated enteric glial gliosis, immune cell infiltrations, and inflammatory responses of CPT-induced piglets. An in vitro experiment with 1 nmol/L RA showed direct protective effects on monocultures of enteric glial cells (EGCs) or macrophages in LPS-simulated inflammatory conditions. Furthermore, 1 ng/mL glial-derived neurotropic factors (GDNF) could inhibit M1-macrophage polarization and pro-inflammatory cytokines production. In summary, VA exerted protective effects on the intestinal barrier by modulating enteric glia and immune cells, perhaps enhancing epithelial recovery under CPT-11 challenge. Our study demonstrated that RA signaling might promote the roles of enteric glia in intestinal immunity and tissue repair, which provided a reference for the VA supplementation of patient diets. Full article
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14 pages, 2097 KiB  
Article
The Role of Calcium, 25-Hydroxyvitamin D, and Parathyroid Hormone in Irritable Bowel Syndrome: A Bidirectional Two-Sample Mendelian Randomization Study
by Ning Xie, Jiale Xie, Ziwei Wang, Qiuai Shu, Haitao Shi, Jinhai Wang, Na Liu, Feng Xu and Jian Wu
Nutrients 2022, 14(23), 5109; https://doi.org/10.3390/nu14235109 - 01 Dec 2022
Cited by 2 | Viewed by 3290
Abstract
Several observational studies have indicated the potential associations among calcium, vitamin D (Vit-D), and irritable bowel syndrome (IBS). However, the causal relationship deduced from these studies is subject to residual confounding factors and reverse causation. Therefore, we aimed to explore the bidirectional causal [...] Read more.
Several observational studies have indicated the potential associations among calcium, vitamin D (Vit-D), and irritable bowel syndrome (IBS). However, the causal relationship deduced from these studies is subject to residual confounding factors and reverse causation. Therefore, we aimed to explore the bidirectional causal effects among serum calcium, Vit-D, PTH, and IBS at the genetic level by a two-sample Mendelian randomization (MR) analysis of the datasets from IEU OpenGWAS database. Sensitivity analyses were performed to evaluate the robustness. The estimates were presented as odds ratios (ORs) with their 95% confidence intervals (CIs). The results of the inverse variance weighted method did not reveal any causal relationship between the genetically predisposed calcium (OR = 0.92, 95% CI: 0.80–1.06, p = 0.25) and Vit-D (OR = 0.99, 95% CI: 0.83–1.19, p = 0.94) level and the risk of IBS. The bidirectional analysis demonstrated that genetic predisposition to IBS was associated with a decreased level of PTH (beta: −0.19, 95%CI: −0.34 to −0.04, p = 0.01). In conclusion, the present study indicates no causal relationship between the serum calcium and Vit-D concentrations and the risk of IBS. The potential mechanisms via which IBS affects serum PTH need to be further investigated. Full article
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14 pages, 2304 KiB  
Article
Electrolyzed Hydrogen Water Alleviates Abdominal Pain through Suppression of Colonic Tissue Inflammation in a Rat Model of Inflammatory Bowel Disease
by Di Hu, Tianliang Huang, Mika Shigeta, Yuta Ochi, Shigeru Kabayama, Yasuyoshi Watanabe and Yilong Cui
Nutrients 2022, 14(21), 4451; https://doi.org/10.3390/nu14214451 - 22 Oct 2022
Cited by 3 | Viewed by 2641
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the digestive tract and is typically accompanied by characteristic symptoms, such as abdominal pain, diarrhea, and bloody stool, severely deteriorating the quality of the patient’s life. Electrolyzed hydrogen water (EHW) has been shown [...] Read more.
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the digestive tract and is typically accompanied by characteristic symptoms, such as abdominal pain, diarrhea, and bloody stool, severely deteriorating the quality of the patient’s life. Electrolyzed hydrogen water (EHW) has been shown to alleviate inflammation in several diseases, such as renal disease and polymyositis/dermatomyositis. To investigate whether and how daily EHW consumption alleviates abdominal pain, the most common symptom of IBD, we examined the antioxidative and anti-inflammatory effects of EHW in an IBD rat model, wherein colonic inflammation was induced by colorectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS). We found that EHW significantly alleviated TNBS-induced abdominal pain and tissue inflammation. Moreover, the production of proinflammatory cytokines in inflamed colon tissue was also decreased significantly. Meanwhile, the overproduction of reactive oxygen species (ROS), which is intricately involved in intestinal inflammation, was significantly suppressed by EHW. Additionally, expression of S100A9, an inflammatory biomarker of IBD, was significantly suppressed by EHW. These results suggest that the EHW prevented the overproduction of ROS due to its powerful free-radical scavenging ability and blocked the crosstalk between oxidative stress and inflammation, thereby suppressing colonic inflammation and alleviating abdominal pain. Full article
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10 pages, 1395 KiB  
Article
Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS
by Xian Qiao, Markos G. Kashiouris, Michael L’Heureux, Bernard J. Fisher, Stefan W. Leichtle, Jonathon D. Truwit, Rahul Nanchal, Robert Duncan Hite, Peter E. Morris, Greg S. Martin, Jonathan Sevransky and Alpha A. Fowler
Nutrients 2022, 14(20), 4415; https://doi.org/10.3390/nu14204415 - 21 Oct 2022
Cited by 14 | Viewed by 2634
Abstract
(1) Background: The disease-modifying mechanisms of high-dose intravenous vitamin C (HDIVC) in sepsis induced acute respiratory distress syndrome (ARDS) is unclear. (2) Methods: We performed a post hoc study of plasma biomarkers from subjects enrolled in the randomized placebo-controlled trial CITRIS-ALI. We explored [...] Read more.
(1) Background: The disease-modifying mechanisms of high-dose intravenous vitamin C (HDIVC) in sepsis induced acute respiratory distress syndrome (ARDS) is unclear. (2) Methods: We performed a post hoc study of plasma biomarkers from subjects enrolled in the randomized placebo-controlled trial CITRIS-ALI. We explored the effects of HDIVC on cell-free DNA (cfDNA) and syndecan-1, surrogates for neutrophil extracellular trap (NET) formation and degradation of the endothelial glycocalyx, respectively. (3) Results: In 167 study subjects, baseline cfDNA levels in HDIVC (84 subjects) and placebo (83 subjects) were 2.18 ng/µL (SD 4.20 ng/µL) and 2.65 ng/µL (SD 3.87 ng/µL), respectively, p = 0.45. At 48-h, the cfDNA reduction was 1.02 ng/µL greater in HDIVC than placebo, p = 0.05. Mean baseline syndecan-1 levels in HDIVC and placebo were 9.49 ng/mL (SD 5.57 ng/mL) and 10.83 ng/mL (SD 5.95 ng/mL), respectively, p = 0.14. At 48 h, placebo subjects exhibited a 1.53 ng/mL (95% CI, 0.96 to 2.11) increase in syndecan-1 vs. 0.75 ng/mL (95% CI, 0.21 to 1.29, p = 0.05), in HDIVC subjects. (4) Conclusions: HDIVC infusion attenuated cell-free DNA and syndecan-1, biomarkers associated with sepsis-induced ARDS. Improvement of these biomarkers suggests amelioration of NETosis and shedding of the vascular endothelial glycocalyx, respectively. Full article
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21 pages, 1139 KiB  
Systematic Review
Systematic Review on Protocols of Coenzyme Q10 Supplementation in Non-Surgical Periodontitis Therapy
by Cordula Leonie Merle, Carina Lenzen, Gerhard Schmalz and Dirk Ziebolz
Nutrients 2023, 15(7), 1585; https://doi.org/10.3390/nu15071585 - 24 Mar 2023
Cited by 1 | Viewed by 1899
Abstract
This systematic review focuses on the different study protocols on CoQ10 as an adjunct in non-surgical periodontitis therapy. The study protocol was developed following PRISMA guidelines and was registered in PROSPERO (CRD42021156887). A sensitive search up to January 2022 considered MEDLINE via PubMed [...] Read more.
This systematic review focuses on the different study protocols on CoQ10 as an adjunct in non-surgical periodontitis therapy. The study protocol was developed following PRISMA guidelines and was registered in PROSPERO (CRD42021156887). A sensitive search up to January 2022 considered MEDLINE via PubMed and Web of Science, Embase, Web of Science Core Collection via Web of Science, Google Scholar, Cochrane CENTRAL, WHO (ICTRP), ClinicalTrials.gov, and grey literature. Randomized controlled (SRP with/without placebo) clinical trials (RCTs) on all types of CoQ10 administration were included. The primary outcome was probing pocket depth (PPD). Secondary outcomes were bleeding on probing, clinical attachment loss, and gingival and plaque indices. Twelve RCTs with local and five with systemic CoQ10 administration were included. The study protocols were heterogeneous. Local CoQ10 administration was performed once or several times in a period up to 15 days. Systemic CoQ10 was applied twice or three times daily for six weeks up to four months. The reporting quality was low, including missing information about CoQ10 doses. Risk of bias was high or unclear. About half of the studies reported significant group differences for PPD. Until now, no statement on the effectiveness of CoQ10 in non-surgical periodontitis therapy is possible. Further high-quality RCTs are necessary and should consider the protocol recommendations of this review. Full article
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