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Perfilyeva YV, Kali A, Aben DS, Abdusattarova YR, Lushova AV, Ostapchuk YO, Tleulieva R, Perfilyeva AV, Sharipov KO, Davlyatshin TI, Abdolla N. Effect of calcitriol on myeloid-derived suppressor cells in physiological aging. J Steroid Biochem Mol Biol 2025; 251:106768. [PMID: 40316223 DOI: 10.1016/j.jsbmb.2025.106768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 03/17/2025] [Accepted: 04/29/2025] [Indexed: 05/04/2025]
Abstract
The active hormonal form of vitamin D, 1,25(OH)2D, regulates many components of the immune system and previous research shows that 1,25(OH)2D reduces the number and suppressive activity of MDSCs in tumors. This study aimed to evaluate the effects of calcitriol treatment on MDSCs in aged mice. We showed that aged BALB/c and CD1 mice exhibited increased levels of CD11b+Gr1+ cells in both the spleen and bone marrow compared to young mice. These cells displayed a less mature phenotype marked by reduced F4/80 expression and demonstrated robust T cell suppressive activity, as evidenced by their ability to inhibit the production of IFNγ and TNFα. Treatment of aged mice with calcitriol, administered twice weekly at a dose equivalent to 1 µg/kg for 4 weeks, significantly increased the population of CD11b+Gr1+ cells in the spleen, but not in the bone marrow of the animals, and promoted their differentiation into a more mature phenotype characterized by elevated F4/80 expression. In addition, calcitriol-treated aged mice exhibited significantly improved T cell responses, as indicated by increased IFNγ production upon specific antigen stimulation compared to the control group of mice. In vitro, calcitriol treatment of bone marrow-derived MDSCs similarly enhanced F4/80 expression without altering other markers such as CD11b, CD11c, or MHCII, and led to reduced expression of reactive oxygen species by these cells. Our study highlights the consistency of MDSC expansion across inbred and outbred mouse strains and supports the immunomodulatory role of calcitriol in promoting MDSC maturation and alleviating immune suppression in aging.
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Affiliation(s)
- Yuliya V Perfilyeva
- M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, 86 Dosmukhamedov St., Almaty 050012, Kazakhstan; Almaty Branch of the National Center for Biotechnology, Central Reference Laboratory, 14 Zhahanger St., Almaty 050054, Kazakhstan
| | - Aikyn Kali
- M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, 86 Dosmukhamedov St., Almaty 050012, Kazakhstan
| | - Diana S Aben
- M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, 86 Dosmukhamedov St., Almaty 050012, Kazakhstan
| | - Yulduz R Abdusattarova
- M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, 86 Dosmukhamedov St., Almaty 050012, Kazakhstan
| | - Anzhelika V Lushova
- M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, 86 Dosmukhamedov St., Almaty 050012, Kazakhstan; Almaty Branch of the National Center for Biotechnology, Central Reference Laboratory, 14 Zhahanger St., Almaty 050054, Kazakhstan; Al-Farabi Kazakh National University, 71 Al-Farabi Avenue, Almaty 050040, Kazakhstan
| | - Yekaterina O Ostapchuk
- M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, 86 Dosmukhamedov St., Almaty 050012, Kazakhstan; Almaty Branch of the National Center for Biotechnology, Central Reference Laboratory, 14 Zhahanger St., Almaty 050054, Kazakhstan
| | - Raikhan Tleulieva
- M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, 86 Dosmukhamedov St., Almaty 050012, Kazakhstan
| | | | - Kamalidin O Sharipov
- M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, 86 Dosmukhamedov St., Almaty 050012, Kazakhstan
| | - Timur I Davlyatshin
- Clinical diagnostic laboratory 'Omikron 3D', 24 Amanzhol St., Almaty 050052, Kazakhstan
| | - Nurshat Abdolla
- M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, 86 Dosmukhamedov St., Almaty 050012, Kazakhstan; Almaty Branch of the National Center for Biotechnology, Central Reference Laboratory, 14 Zhahanger St., Almaty 050054, Kazakhstan.
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Shekhawat DS, Singh K, Singh P, Vyas V, Varthya SB, Sharma P. Prenatal vitamin D levels and infant cognitive, motor, language and social-emotional development at 6 and 9 months of age. Nutr Neurosci 2025; 28:263-272. [PMID: 38896552 DOI: 10.1080/1028415x.2024.2366649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/21/2024]
Abstract
AIM Vitamin D is involved in several processes related to the development of neuronal and non-neuronal cells. There is a possible link between maternal vitamin D status in pregnancy and delayed neurocognitive development in the offspring. The aim of the study was to explore the association of maternal and cord blood vitamin D levels with infants' neurodevelopment at 6 and 9 months of age. METHODOLOGY A cohort study was conducted in western Rajasthan, India. Maternal and cord blood samples were collected at the time of delivery. Serum 25(OH)-vitamin D levels were measured in both. Infant neurodevelopment was assessed at 6 and 9 months of age in six domains namely cognitive, receptive language, expressive language, fine motor, gross motor and social-emotional using the Bayley Scale of Infant Development- III (BSID-III). RESULTS A total of 175 mother-child pairs were enrolled. Among the mothers taking part in this study, 7.3% had deficient and 59.09% had insufficient levels of serum 25(OH) vitamin D during the third trimester of their pregnancy. Maternal and cord blood serum 25-OH vitamin D levels were 18.86 ± 8.53 ng/mL and 17.39 ± 8.87 ng/mL, respectively, and there was a significant correlation (r = 0.9778, p = 0.000) between levels of vitamin D. Based on the repeated measures ANOVA, post hoc Tukey's HSD test, maternal vitamin D levels had a significant relationship (p = 0.047) to the cognitive development of infants at 6 months of age. Furthermore, cord serum vitamin D levels showed a significant association (p = 0.023 and p = 0.010) with the social-emotional development of the infant at the age of 6 and 9 months. CONCLUSION Maternal and cord serum 25-OH vitamin D deficiency was significantly associated with the cognitive and social-emotional development of infants.
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Affiliation(s)
| | - Kuldeep Singh
- Department of Pediatrics, All India Institute of Medical Sciences, Jodhpur, India
| | - Pratibha Singh
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, Jodhpur, India
| | - Varuna Vyas
- Department of Pediatrics, All India Institute of Medical Sciences, Jodhpur, India
| | - Shoban Babu Varthya
- Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, India
| | - Praveen Sharma
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India
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Ducki C, Wojtkiewicz M, Bartoszewicz M, Fiedor P. The Role of Vitamin D in Rare Diseases-A Clinical Review. Biomedicines 2025; 13:558. [PMID: 40149535 PMCID: PMC11940540 DOI: 10.3390/biomedicines13030558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Revised: 02/11/2025] [Accepted: 02/14/2025] [Indexed: 03/29/2025] Open
Abstract
Background/Objectives: Patients suffering from rare diseases are particularly vulnerable to vitamin D deficiency. The role of vitamin D status in rare disease management remains insufficiently investigated and employed in routine clinical practice. Methods: This review analyses current data on vitamin D status in selected rare diseases of organs involved in vitamin D metabolism: skin (epidermolysis bullosa, morphea), liver (autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis), kidney (Alport syndrome, Fabry disease), and cystic fibrosis as a model of a systemic rare disease. Additionally, this review critically examines potential drug-vitamin D interactions in the context of rare disease patient polypharmacy. Results: Evidence suggests that vitamin D deficiency is prevalent in rare disease patient populations, often at once exacerbating and being simultaneously exacerbated by the underlying condition. Vitamin D deficiency correlates with worse clinical outcomes and lower quality of life across the examined diseases. Immunoregulatory properties of vitamin D appear relevant for rare diseases with autoimmune components. Conclusions: An urgent need for developing disease-specific clinical practice guidelines, implementing routine vitamin D monitoring in rare disease patient care, and introducing tailored supplementation under the principles of precision medicine is emphasized.
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Affiliation(s)
- Czesław Ducki
- Mazovian Specialized Health Center in Pruszków, Partyzantów 2/4, 05-802 Pruszków, Poland
- University of Economics and Human Sciences in Warsaw, Okopowa 59, 01-043 Warsaw, Poland; (M.W.); (M.B.)
| | - Marta Wojtkiewicz
- University of Economics and Human Sciences in Warsaw, Okopowa 59, 01-043 Warsaw, Poland; (M.W.); (M.B.)
- Medical University of Warsaw, Żwirki i Wigury 61, 02-091 Warsaw, Poland
| | - Marcin Bartoszewicz
- University of Economics and Human Sciences in Warsaw, Okopowa 59, 01-043 Warsaw, Poland; (M.W.); (M.B.)
| | - Piotr Fiedor
- University of Economics and Human Sciences in Warsaw, Okopowa 59, 01-043 Warsaw, Poland; (M.W.); (M.B.)
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Hudson BT, Dubrof ST, Settles SE, Park HJ, Filipov NM. Effects of maternal supplementation with DHA and/or egg yolk powder on monoamine homeostasis in the perinatal piglet brain. Nutr Neurosci 2025; 28:18-27. [PMID: 38662810 DOI: 10.1080/1028415x.2024.2344138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
OBJECTIVES Reports indicate that children of mothers who received docosahexaenoic acid (DHA) or egg yolk supplements during pregnancy have improved performance on cognitive tasks and brain growth; their combination has recently been demonstrated to modulate functional neuronal network connectivity in the human-relevant piglet brain. To expand upon this functional connectivity analysis, neurochemical evaluation to determine how dietary supplementation with one or both of these nutrients during the last trimester of pregnancy alters monoamine homeostasis in selected brain regions of piglets was done. METHODS Beginning gestation days 60-69 through weaning, pregnant sows were fed either control diet or diets supplemented with egg yolk powder, DHA, or both. Brains were then collected, and monoamine neurotransmitters and their metabolites were quantified from various brain regions with HPLC-ECD. RESULTS Relative to controls, egg yolk supplementation increased serotonin metabolite (5-HIAA) levels in the cerebellum, while DHA supplementation decreased serotonin (5-HT) levels in the prefrontal cortex; combined supplementation increased norepinephrine metabolite (MHPG) levels in the prefrontal cortex and cerebellum, but decreased 5-HT levels in the posterior hippocampus. Notably, all diets increased serotonin, dopamine, and their respective metabolite levels in the substantia nigra. DISSCUSSION This suggests both overlapping and specific effects of DHA and components of egg yolk in the context of maternal supplementation during pregnancy and lactation that might facilitate optimal neurodevelopment, with the nigrostriatal pathway being particularly sensitive. Such supplementations might impact brain function and facilitate development later in life through modulating monoamine homeostasis.
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Affiliation(s)
- Brice T Hudson
- Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA
| | - Stephanie T Dubrof
- Department of Nutritional Sciences, College of Family and Consumer Sciences, University of Georgia, Athens, GA, USA
| | - Skylar E Settles
- Department of Genetics, Franklin College of Arts and Sciences, University of Georgia, Athens, GA, USA
| | - Hea J Park
- Department of Nutritional Sciences, College of Family and Consumer Sciences, University of Georgia, Athens, GA, USA
| | - Nikolay M Filipov
- Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA
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Nuti R, Gennari L, Cavati G, Caffarelli C, Frediani B, Gonnelli S, Catalano A, Francucci CM, Laurentaci C, Letizia Mauro G, Malavolta N, Mazzantini M, Minisola G, Russo R, Sabatino P, Pinto M, Salomone S, Tei L, Vescini F, Xourafa A, Cartocci A, Lo Conte S, Merlotti D. Analysis of Usual Consumption of Vitamin D Among Adult Individuals in Italy. Nutrients 2024; 16:4194. [PMID: 39683587 DOI: 10.3390/nu16234194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 11/27/2024] [Accepted: 11/29/2024] [Indexed: 12/18/2024] Open
Abstract
Background: The condition of vitamin D (25OHD) deficiency represents an important public health problem. In Europe, hypovitaminosis is common not only in the elderly population but also between 50 and 70 years, both in males and females. Data regarding vitamin D intake in the Italian population are very limited. In a recent paper, reporting data collected by a specific Frequency Food Questionnaire (FFQ), we observed in a small group of healthy subjects that the dietary consumption of vitamin D, both in females and males, was far below the average. Methods: With the aim of expanding our preliminary data, we conducted a survey on a large cohort of subjects from different areas of Northern, Central, and Southern Italy. The FFQ contained 11 different questions regarding the amount and type of intake of foods containing ergocalciferol and cholecalciferol. It was submitted to 870 subjects, 627 females and 243 males, with an age range from 40 to 80 years; 31.6% of the studied population was apparently in good health, while 68.4% were affected by different pathologies. Results: The present data confirm previous observations: the global quantity of vitamin D intake in 14 days was 70.8 μg (±1.8 SE, ±54.4 SD) in females and 87.5 μg (±1.9 SE, ±57.1 SD) in males; the mean daily intake of vitamin D in females and males was 5.05 μg (±0.5 SE, ±3.8 SD) and 6.25 μg (±0.21 SE, ±4.1 SD), respectively. In healthy subjects, a gradual decrease was observed in the overall intake of vitamin D in both females and males according to an increase in age bracket, ranging from 74.5 μg and 103.8 μg in the 40-50 age group to 54.5 μg and 87.8 μg in the 71-80 age group, respectively. Conclusions: In conclusion, the present data, collected in a large Italian cohort, underscore that the daily intake of vitamin D is far below the recommended daily average, thereby contributing to the development of potential hypovitaminosis.
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Affiliation(s)
- Ranuccio Nuti
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
| | - Luigi Gennari
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
| | - Guido Cavati
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
| | - Carla Caffarelli
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
| | - Bruno Frediani
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
| | - Stefano Gonnelli
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
| | - Antonino Catalano
- Department of Clinical and Experimental Medicine, University of Messina, 98121 Messina, Italy
| | - Cristiano Maria Francucci
- Istituto Nazionale di Ricovero e Cura per Anziani Istituti di Ricovero e Cura a Carattere Scientifico, 60124 Ancona, Italy
| | | | - Giulia Letizia Mauro
- Dipartimento delle Discipline Chirurgiche, Oncologiche e Stomatologiche, University of Palermo, 90121 Palermo, Italy
| | | | | | | | - Raffaella Russo
- Department of Medical and Surgical Science, University Magna Grecia, 88100 Catanzaro, Italy
| | | | - Monica Pinto
- Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80138 Napoli, Italy
| | | | - Luciano Tei
- Italian Study Group on Metabolic Bone Disorders (GISMO), 00132 Rome, Italy
| | - Fabio Vescini
- Azienda Ospedaliera Universitaria Santa Maria della Misericordia, 33100 Udine, Italy
| | - Anastasia Xourafa
- Azienda Ospedaliera Universitaria Policlinico "G. Rodolico-San Marco", 95100 Catania, Italy
| | - Alessandra Cartocci
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
| | - Sofia Lo Conte
- Department of Medical Sciences, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy
| | - Daniela Merlotti
- Department of Medical Sciences, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy
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Kobayashi H, Amrein K, Mahmoud SH, Lasky-Su JA, Christopher KB. Metabolic phenotypes and vitamin D response in the critically ill: A metabolomic cohort study. Clin Nutr 2024; 43:10-19. [PMID: 39307095 DOI: 10.1016/j.clnu.2024.09.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 09/07/2024] [Accepted: 09/14/2024] [Indexed: 10/26/2024]
Abstract
BACKGROUND & AIMS Although vitamin D deficiency is common in critically ill patients, randomized controlled trials fail to demonstrate benefits of supplementation. We aimed to identify distinct vitamin D3 responsive metabolic phenotypes prior to trial intervention of high-dose vitamin D3 by applying machine learning clustering method to metabolomics data from the Correction of Vitamin D Deficiency in Critically Ill Patients (VITdAL-ICU) trial. METHODS In the randomized, placebo-controlled VITdAL-ICU trial, critically ill adults received placebo or high-dose vitamin D3. To distinguish vitamin D3 responsive metabolic phenotypes prior to intervention, we implemented consensus clustering with partitioning around medoids algorithm to the plasma metabolome data before randomization. Individual metabolite differences were determined utilizing linear mixed-effects regression models stratified for metabolomic phenotypes with false discovery rate adjustment. The association between vitamin D3 supplementation and 180-day mortality was evaluated in each metabolic phenotype, applying multivariable logistic regression analysis. RESULTS In 453 critically ill adults, the study identified 4 distinct metabolic phenotypes (clusters A. N = 134; B. N = 123; C. N = 92; D. N = 104). We found differential metabolic pathway patterns in the four clusters. Specifically, branched chain amino acid catabolic metabolites, long-chain acylcarnitines and diacylglycerol species are significantly increased in a specific metabolic phenotype (cluster D) following high-dose vitamin D3. Further, in cluster D high-dose vitamin D3 supplementation had a significantly lower adjusted odds of 180-day mortality after controlling age, sex, Simplified Acute Physiology Score II, admission diagnosis, and baseline 25-hydroxyvitamin D (OR 0.28 (95%CI, 0.09-0.89); P = 0.03). In metabotype A, B, and C, high-dose vitamin D3 supplementation was not significantly associated with lower 180-day mortality following multivariable adjustment. CONCLUSION In this post-hoc cohort study of the VITdAL-ICU trial, the clustering analysis of plasma metabolome data identified biologically distinct metabolic phenotypes. Among clusters, we found the different associations between high-dose vitamin D3 supplementation and specific metabolite pathways as well as 180-day mortality. Our findings facilitate further research to validate metabolic phenotype-targeted strategies for critical illness treatments.
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Affiliation(s)
- Hirotada Kobayashi
- Department of Critical Care Medicine, Sunnybrook Health Sciences Center, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada; Interdepartmental Division of Critical Care Medicine, University of Toronto, 204 Victoria Street, Toronto, ON M5B 1T8, Canada
| | - Karin Amrein
- Division of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
| | - Sherif H Mahmoud
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 116 St. and 85 Ave, Edmonton, Alberta T6G 2R3, Canada
| | - Jessica A Lasky-Su
- Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, USA
| | - Kenneth B Christopher
- Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, USA; Division of Renal Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, USA.
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Zhou QL, Ye D, Ren PC, Pang WB, Lin XM, Cao RH, Ye XS, Xiang W, Xiao L. A multi-omics analysis reveals vitamin D supplementation since childhood modulates molecules for signal transductions in the mouse striatum. Biomed Pharmacother 2024; 178:117145. [PMID: 39038374 DOI: 10.1016/j.biopha.2024.117145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 07/02/2024] [Accepted: 07/11/2024] [Indexed: 07/24/2024] Open
Abstract
Vitamin D is a critical fat-soluble vitamin for the nervous system. Research suggests a potential link between vitamin D deficiency and attention-deficit hyperactivity disorder (ADHD), particularly in children and adolescents. The core symptoms of ADHD are associated with deficits in striatal functions, and maintaining sufficient levels of vitamin D may help prevent or alleviate ADHD symptoms. However, the molecular changes in the striatum caused by vitamin D supplementation that may contribute to the brain processes linked to ADHD symptoms remain unclear. In this study, we established a mouse model fed diets with three different dose gradients of vitamin D3 (0, 500, and 2000 IU/kg·day) from postnatal day 21 (P21) to 14 weeks of age. Striatal tissues from mice with gradient vitamin D3 intake were subjected to reduced representation bisulfite sequencing (RRBS), RNA-sequencing, and neurotransmitter profiling by liquid chromatography-mass spectrometry (LC-MS). Our findings indicate that vitamin D supplementation since childhood influenced the overall landscape of DNA methylations and the expression of many genes involved in critical neurological functions in a dose-dependent manner. Additionally, our data demonstrate how vitamin D modulated neuropeptide signaling pathways, as well as cholinergic and dopaminergic synapses in the striatum, through an orchestrated mechanism involving epigenetic and transcriptional regulations. Furthermore, we observed a synergistic effect of vitamin D on dopamine release following acute methylphenidate injection into our mouse model. In summary, this study provides mechanistic insights into how dietary vitamin D supplementation since childhood can modulate specific signal transductions among striatal cells, underscoring the importance of vitamin D supplementation for ADHD management.
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Affiliation(s)
- Q L Zhou
- Hainan Women and Children's Medical Center, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China; School of Basic Medicine and Life Science, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China
| | - D Ye
- Hainan Women and Children's Medical Center, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China; School of Pediatrics, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China
| | - P C Ren
- Hainan Women and Children's Medical Center, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China; School of Basic Medicine and Life Science, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China
| | - W B Pang
- School of Pediatrics, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China
| | - X M Lin
- Hainan Women and Children's Medical Center, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China; School of Basic Medicine and Life Science, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China
| | - R H Cao
- Hainan Women and Children's Medical Center, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China; School of Pediatrics, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China
| | - X S Ye
- School of Pediatrics, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China
| | - W Xiang
- Hainan Women and Children's Medical Center, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China; School of Pediatrics, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China.
| | - L Xiao
- Hainan Women and Children's Medical Center, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China; School of Pediatrics, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China.
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D’Amuri A, Greco S, Pagani M, Presciuttini B, Ciaffi J, Ursini F. Common Non-Rheumatic Medical Conditions Mimicking Fibromyalgia: A Simple Framework for Differential Diagnosis. Diagnostics (Basel) 2024; 14:1758. [PMID: 39202246 PMCID: PMC11354086 DOI: 10.3390/diagnostics14161758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 08/06/2024] [Accepted: 08/10/2024] [Indexed: 09/03/2024] Open
Abstract
Fibromyalgia (FM) is a chronic non-inflammatory disorder mainly characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and a constellation of other symptoms. For this reason, delineating a clear distinction between pure FM and FM-like picture attributable to other common diseases can be extremely challenging. Physicians must identify the most significant confounders in individual patients and implement an appropriate diagnostic workflow, carefully choosing a minimal (but sufficient) set of tests to be used for identifying the most plausible diseases in the specific case. This article discusses prevalent non-rheumatological conditions commonly observed in the general population that can manifest with clinical features similar to primary FM. Given their frequent inclusion in the differential diagnosis of FM patients, the focus will be on elucidating the distinctive clinical characteristics of each condition. Additionally, the most cost-effective and efficient diagnostic methodologies for accurately discerning these conditions will be examined.
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Affiliation(s)
- Andrea D’Amuri
- General Medicine Unit, Medical Department, ASST Mantova, Ospedale Carlo Poma, Str. Lago Paiolo 10, 46100 Mantova, Italy; (A.D.); (M.P.); (B.P.)
| | - Salvatore Greco
- Internal Medicine Unit, Medical Department, Ospedale del Delta, Via Valle Oppio 2, Lagosanto, 44023 Ferrara, Italy;
| | - Mauro Pagani
- General Medicine Unit, Medical Department, ASST Mantova, Ospedale Carlo Poma, Str. Lago Paiolo 10, 46100 Mantova, Italy; (A.D.); (M.P.); (B.P.)
| | - Barbara Presciuttini
- General Medicine Unit, Medical Department, ASST Mantova, Ospedale Carlo Poma, Str. Lago Paiolo 10, 46100 Mantova, Italy; (A.D.); (M.P.); (B.P.)
| | - Jacopo Ciaffi
- Medicine & Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy;
- Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, 40136 Bologna, Italy
| | - Francesco Ursini
- Medicine & Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy;
- Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, 40136 Bologna, Italy
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Alimohammadi‐Kamalabadi M, Ziaei S, Hasani M, Mohammadi S, Mehrbod M, Morvaridi M, Persad E, Belančić A, Malekahmadi M, Estêvão MDDMADO, Daneshzad E, Heshmati J. Does vitamin D supplementation impact serotonin levels? A systematic review and meta-analysis. Health Sci Rep 2024; 7:e2276. [PMID: 39086509 PMCID: PMC11287715 DOI: 10.1002/hsr2.2276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 06/10/2024] [Accepted: 07/10/2024] [Indexed: 08/02/2024] Open
Abstract
Background and Aims Vitamin D deficiency impacts a significant proportion of the world's population, and this deficiency has been linked to various conditions characterized by imbalanced serotonin regulation. The objective of this systematic review and meta-analysis was to evaluate the effect of vitamin D supplementation on serum serotonin levels. Methods We conducted a comprehensive search of PubMed, Scopus, Cochrane Central for Randomized Clinical Trials, and Web of Science up to September 2022, without any language restrictions. The effect sizes were calculated using the standard mean difference (SMD) and 95% confidence interval (CI). Results Six randomized clinical trials involving 356 participants were included in the analysis. Our findings indicated no significant changes in serotonin levels between the intervention and control groups (SMD: 0.24 ng/mL, 95% CI: -0.28, 0.75, p > 0.10). Subgroup analysis also did not reveal any significant changes in serotonin levels among children, participants with autism spectrum disorders, interventions lasting 10 weeks or longer, or those receiving vitamin D doses below 4000 IU/day. Conclusion Although the results obtained in this systematic review are inconclusive, they support the need for further well-designed randomized trials to assess the potential role of vitamin D supplementation in regulating serotonin levels and potentially ameliorating depression and related disorders.
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Affiliation(s)
- Malek Alimohammadi‐Kamalabadi
- Department of Cellular‐Molecular Nutrition, School of Nutritional Sciences and DieteticsTehran University of Medical SciencesTehranIran
| | - Somayeh Ziaei
- ICU Department, Emam Reza HospitalKermanshah University of Medical SciencesKermanshahIran
| | - Motahareh Hasani
- Department of Nutritional Sciences, School of HealthGolestan University of Medical SciencesGorganIran
| | - Shooka Mohammadi
- Department of Social and Preventive Medicine, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
| | - Milad Mehrbod
- Department of Internal Medicine, Faculty of MedicineTehran University of Medical SciencesTehranIran
| | - Mehrnaz Morvaridi
- Department of Nutrition, School of Public HealthIran University of Medical SciencesTehranIran
| | - Emma Persad
- Department for Evidence‐based Medicine and EvaluationDanube University KremsKremsAustria
| | - Andrej Belančić
- Department of Basic and Clinical Pharmacology with Toxicology, Faculty of MedicineUniversity of RijekaRijekaCroatia
| | - Mahsa Malekahmadi
- Imam Khomeini Hospital ComplexTehran University of Medicinal Sciences Tehran Iran, Tehran University of Medical SciencesTehranIran
| | | | - Elnaz Daneshzad
- Non‐Communicable Diseases Research CenterAlborz University of Medical SciencesKarajIran
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10
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Johnson JR, Martini RN, Yuan YC, Woods-Burnham L, Walker M, Ortiz-Hernandez GL, Kobeissy F, Galloway D, Gaddy A, Oguejiofor C, Allen B, Lewis D, Davis MB, Kimbro KS, Yates CC, Murphy AB, Kittles RA. 1,25-Dihydroxyvitamin D 3 Suppresses Prognostic Survival Biomarkers Associated with Cell Cycle and Actin Organization in a Non-Malignant African American Prostate Cell Line. BIOLOGY 2024; 13:346. [PMID: 38785827 PMCID: PMC11118023 DOI: 10.3390/biology13050346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 05/09/2024] [Accepted: 05/10/2024] [Indexed: 05/25/2024]
Abstract
Vitamin D3 is a steroid hormone that confers anti-tumorigenic properties in prostate cells. Serum vitamin D3 deficiency has been associated with advanced prostate cancer (PCa), particularly affecting African American (AA) men. Therefore, elucidating the pleiotropic effects of vitamin D on signaling pathways, essential to maintaining non-malignancy, may provide additional drug targets to mitigate disparate outcomes for men with PCa, especially AA men. We conducted RNA sequencing on an AA non-malignant prostate cell line, RC-77N/E, comparing untreated cells to those treated with 10 nM of vitamin D3 metabolite, 1α,25(OH)2D3, at 24 h. Differential gene expression analysis revealed 1601 significant genes affected by 1α,25(OH)2D3 treatment. Pathway enrichment analysis predicted 1α,25(OH)2D3- mediated repression of prostate cancer, cell proliferation, actin cytoskeletal, and actin-related signaling pathways (p < 0.05). Prioritizing genes with vitamin D response elements and associating expression levels with overall survival (OS) in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) cohort, we identified ANLN (Anillin) and ECT2 (Epithelial Cell Transforming 2) as potential prognostic PCa biomarkers. Both genes were strongly correlated and significantly downregulated by 1α,25(OH)2D3 treatment, where low expression was statistically associated with better overall survival outcomes in the TCGA PRAD public cohort. Increased ANLN and ECT2 mRNA gene expression was significantly associated with PCa, and Gleason scores using both the TCGA cohort (p < 0.05) and an AA non-malignant/tumor-matched cohort. Our findings suggest 1α,25(OH)2D3 regulation of these biomarkers may be significant for PCa prevention. In addition, 1α,25(OH)2D3 could be used as an adjuvant treatment targeting actin cytoskeleton signaling and actin cytoskeleton-related signaling pathways, particularly among AA men.
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Affiliation(s)
- Jabril R. Johnson
- Department of Microbiology, Biochemistry, & Immunology, Morehouse School of Medicine, 720 Westview Drive, Atlanta, GA 30310, USA
- Institute of Translational Genomic Medicine, Morehouse School of Medicine, 720 Westview Drive, Atlanta, GA 30310, USA
| | - Rachel N. Martini
- Department of Microbiology, Biochemistry, & Immunology, Morehouse School of Medicine, 720 Westview Drive, Atlanta, GA 30310, USA
- Institute of Translational Genomic Medicine, Morehouse School of Medicine, 720 Westview Drive, Atlanta, GA 30310, USA
| | - Yate-Ching Yuan
- Department of Computational Quantitative Medicine, Center for Informatics, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA
| | - Leanne Woods-Burnham
- Department of Physiology, Morehouse School of Medicine, 720 Westview Drive, Atlanta, GA 30310, USA
| | - Mya Walker
- Department of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA
| | - Greisha L. Ortiz-Hernandez
- Department of Population Sciences, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA
| | - Firas Kobeissy
- Department of Neurobiology, Center for Neurotrauma, Multiomics & Biomarkers (CNMB), Neuroscience Institute, Morehouse School of Medicine, 720 Westview Dr SW, Atlanta, GA 30310, USA
| | - Dorothy Galloway
- Department of Population Sciences, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA
| | - Amani Gaddy
- Department of Microbiology, Biochemistry, & Immunology, Morehouse School of Medicine, 720 Westview Drive, Atlanta, GA 30310, USA
| | - Chidinma Oguejiofor
- Department of Microbiology, Biochemistry, & Immunology, Morehouse School of Medicine, 720 Westview Drive, Atlanta, GA 30310, USA
| | - Blake Allen
- Department of Microbiology, Biochemistry, & Immunology, Morehouse School of Medicine, 720 Westview Drive, Atlanta, GA 30310, USA
| | - Deyana Lewis
- Department of Community Health and Preventive Medicine, Morehouse School of Medicine, 720 Westview Drive, Atlanta, GA 30310, USA
| | - Melissa B. Davis
- Department of Microbiology, Biochemistry, & Immunology, Morehouse School of Medicine, 720 Westview Drive, Atlanta, GA 30310, USA
- Institute of Translational Genomic Medicine, Morehouse School of Medicine, 720 Westview Drive, Atlanta, GA 30310, USA
| | - K. Sean Kimbro
- Department of Microbiology, Biochemistry, & Immunology, Morehouse School of Medicine, 720 Westview Drive, Atlanta, GA 30310, USA
| | - Clayton C. Yates
- Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Adam B. Murphy
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Rick A. Kittles
- Department of Community Health and Preventive Medicine, Morehouse School of Medicine, 720 Westview Drive, Atlanta, GA 30310, USA
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11
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Carboo JA, Dolman-Macleod RC, Malan L, Lombard MJ. High-dose oral vitamin D supplementation for prevention of infections in children aged 0 to 59 months: a systematic review and meta-analysis. Nutr Rev 2024; 82:579-599. [PMID: 37428896 PMCID: PMC11009788 DOI: 10.1093/nutrit/nuad082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/12/2023] Open
Abstract
CONTEXT Vitamin D plays an important role in immune function, and the deficiency thereof has been associated with several infections, most notably respiratory tract infections. However, data from intervention studies investigating the effect of high-dose vitamin D supplementation on infections have been inconclusive. OBJECTIVE The aim of this study was to evaluate the level of evidence regarding the efficacy of vitamin D supplementation above the standard dose (400 IU) in preventing infections in apparently healthy children < 5 years of age. DATA SOURCES PubMed, Scopus, Science Direct, Web of Science, Google Scholar, CINAHL, and MEDLINE electronic databases were searched between August 2022 and November 2022. Seven studies met the inclusion criteria. DATA EXTRACTION Meta-analyses of outcomes in more than one study were performed using Review Manager software. Heterogeneity was evaluated using the I2 statistic. Randomized controlled trials in which vitamin D was supplemented at > 400 IU compared with placebo, no treatment, or standard dose were included. DATA ANALYSIS Seven trials that enrolled a total of 5748 children were included. Odds ratios (ORs) with 95%CIs were calculated using random- and fixed-effects models. There was no significant effect of high-dose vitamin D supplementation on the incidence of upper respiratory tract infection (OR, 0.83; 95%CI, 0.62-1.10). There was a 57% (95%CI, 0.30-0.61), 56% (95%CI, 0.27-0.07), and 59% (95%CI, 0.26-0.65) reduction in the odds of influenza/cold, cough, and fever incidence, respectively, with daily supplementation of vitamin D > 1000 IU. No effect was found on bronchitis, otitis media, diarrhea/gastroenteritis, primary care visits for infections, hospitalizations, or mortality. CONCLUSION High-dose vitamin D supplementation provided no benefit in preventing upper respiratory tract infections (moderate certainty of evidence) but reduced the incidence influenza/cold (moderate certainty of evidence), cough, and fever (low certainty of evidence). These findings are based on a limited number of trials and should be interpreted with caution. Further research is needed. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration number CRD42022355206.
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Affiliation(s)
- Janet Adede Carboo
- Centre of Excellence for Nutrition (CEN), North-West University, Potchefstroom, North West Province, South Africa
| | - Robin Claire Dolman-Macleod
- Centre of Excellence for Nutrition (CEN), North-West University, Potchefstroom, North West Province, South Africa
| | - Linda Malan
- Centre of Excellence for Nutrition (CEN), North-West University, Potchefstroom, North West Province, South Africa
| | - Martani Johanni Lombard
- Centre of Excellence for Nutrition (CEN), North-West University, Potchefstroom, North West Province, South Africa
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12
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Hasan M, Reyer H, Oster M, Trakooljul N, Ponsuksilli S, Magowan E, Fischer DC, Wimmers K. Exposure to artificial ultraviolet-B light mediates alterations on the hepatic transcriptome and vitamin D metabolism in pigs. J Steroid Biochem Mol Biol 2024; 236:106428. [PMID: 37984748 DOI: 10.1016/j.jsbmb.2023.106428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 10/28/2023] [Accepted: 11/17/2023] [Indexed: 11/22/2023]
Abstract
In the currently prevailing pig husbandry systems, the vitamin D status is almost exclusively dependent on dietary supply. Additional endogenous vitamin D production after exposure to ultraviolet-B (UVB) light might allow the animals to utilize minerals in a more efficient manner, as well as enable the production of functional vitamin D-enriched meat for human consumption. In this study, growing pigs (n = 16) were subjected to a control group or to a daily narrowband UVB exposure of 1 standard erythema dose (SED) for a period of 9 weeks until slaughter at a body weight of 105 kg. Transcriptomic profiling of liver with emphasis on the associated effects on vitamin D metabolism due to UVB exposure were evaluated via RNA sequencing. Serum was analyzed for vitamin D status and health parameters such as minerals and biochemical markers. The serum concentration of calcidiol, but not calcitriol, was significantly elevated in response to UVB exposure after 17 days on trial. No effects of UVB exposure were observed on growth performance and blood test results. At slaughter, the RNA sequencing analyses following daily UVB exposure revealed 703 differentially expressed genes (DEGs) in liver tissue (adjusted p-value < 0.01). Results showed that molecular pathways for vitamin D synthesis (CYP2R1) rather than cholesterol synthesis (DHCR7) were preferentially initiated in liver. Gene enrichment (p < 0.05) was observed for reduced cholesterol/steroid biosynthesis, SNARE interactions in vesicular transport, and CDC42 signaling. Taken together, dietary vitamin D supply can be complemented via endogenous production after UVB exposure in pig husbandry, which could be considered in the development of functional foods.
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Affiliation(s)
- Maruf Hasan
- Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
| | - Henry Reyer
- Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
| | - Michael Oster
- Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
| | - Nares Trakooljul
- Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
| | | | - Elizabeth Magowan
- Agri-Food and Biosciences Institute, Large Park, Hillsborough, Co Down, BT26 6DR, United Kingdom
| | - Dagmar-Christiane Fischer
- Department of Pediatrics, Rostock University Medical Center, Ernst-Heydemann-Str. 8, 18057 Rostock, Germany
| | - Klaus Wimmers
- Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany; Faculty of Agricultural and Environmental Sciences, University Rostock, Rostock, Germany.
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13
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Alliband KH, Parr T, Jethwa PH, Brameld JM. Active vitamin D increases myogenic differentiation in C2C12 cells via a vitamin D response element on the myogenin promoter. Front Physiol 2024; 14:1322677. [PMID: 38264331 PMCID: PMC10804454 DOI: 10.3389/fphys.2023.1322677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 12/14/2023] [Indexed: 01/25/2024] Open
Abstract
Background: Skeletal muscle development during embryogenesis depends on proliferation of myoblasts followed by differentiation into myotubes/multinucleated myofibers. Vitamin D (VD) has been shown to affect these processes, but there is conflicting evidence within the current literature on the exact nature of these effects due to a lack of time course data. With 20%-40% of pregnant women worldwide being VD deficient, it is crucial that a clearer understanding of the impact of VD on myogenesis is gained. Methods: A detailed 8-day differentiation time course was used where C2C12 cells were differentiated in control media (2% horse serum) or with different concentrations of active VD, 1,25 (OH)2D3 (10-13 M, 10-11 M, 10-9 M or 10-7 M), and measurements were taken at 6 time points. DNA, creatine kinase and protein assays were carried out as well as quantitative PCR to determine expression of Myf5, MyoD, myogenin, MHC I, and MHC neonatal, MHC embryonic, MHC IIa, MHC IIx, and MHC IIb mRNAs. Transfections were carried out using one vector containing the myogenin promoter and another containing the same promoter with a 3 base mutation within a putative vitamin D response element (VDRE) to determine effects of 1,25 (OH)2D3 on myogenin transcription. Finally, a ChIP assay was performed to determine whether the VD receptor (VDR) binds to the putative VDRE. Results: 1,25(OH)2D3 caused an inhibition of proliferation and an increase in differentiation in C2C12 cells. Myf5, myogenin, MHC I, and MHC neonatal, MHC embryonic, MHC IIa, MHC IIx, and MHC IIb expression were all increased by 1,25(OH)2D3. Myotube size was also increased by VD. When the putative VDRE on the myogenin promoter was mutated, the increase in expression by VD was lost. ChIP analysis revealed that the VDR does bind to the putative VDRE on the myogenin promoter. Conclusion: Active VD directly increases myogenin transcription via a functional VDRE on the myogenin promoter, resulting in increased myogenic differentiation, increased expression of both the early and late MHC isoforms, and also increased myotube size. These results highlight the importance of VD status during pregnancy for normal myogenesis to occur, but further in vivo work is needed.
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Affiliation(s)
| | | | | | - John M. Brameld
- Division of Food, Nutrition and Dietetics, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, United Kingdom
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14
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Al-Kuraishy HM, Al-Gareeb AI, Selim HM, Alexiou A, Papadakis M, Negm WA, Batiha GES. Does vitamin D protect or treat Parkinson's disease? A narrative review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:33-40. [PMID: 37555855 PMCID: PMC10771600 DOI: 10.1007/s00210-023-02656-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 07/30/2023] [Indexed: 08/10/2023]
Abstract
Parkinson's disease (PD) is a neurodegenerative brain disease (NBD) developed due to dopaminergic neuron loss in the substantia nigra (SN). Vitamin D (VD), VD receptor (VDR), and VD metabolites are highly expressed in the human brain and play a critical role in maintaining different brain functions. VDRs are highly expressed in the SN that regulates the activity of dopaminergic neurons and synaptic plasticity. VD exerts protective and therapeutic effects against the development of PD by modulating dopaminergic neurons of SN. VD reduces oxidative stress and neuroinflammation in PD because of its anti-inflammatory and antioxidant activities. Different studies revealed the protective effect of VD in the management of PD. However, the potential therapeutic effect of VD in well-established PD remains controversial. Therefore, this review aims to elucidate VD's preventive and therapeutic roles in PD. In conclusion, VD deficiency is associated with increased PD risk, but VD supplementation in well-established PD plays little role.
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Affiliation(s)
- Hayder M Al-Kuraishy
- Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, 14132, Iraq
| | - Ali I Al-Gareeb
- Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, 14132, Iraq
| | - Hend Mostafa Selim
- Biochemistry Department, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt
| | - Athanasios Alexiou
- Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW, 2770, Australia
- AFNP Med, 1030, Wien, Austria
| | - Marios Papadakis
- Department of Surgery II, University Hospital Witten-Herdecke, Heusnerstrasse 40, University of Witten-Herdecke, 42283, Wuppertal, Germany.
| | - Walaa A Negm
- Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt.
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt.
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15
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Tuma C, Schick A, Pommerening N, Braun H, Thevis M. Effects of an Individualized vs. Standardized Vitamin D Supplementation on the 25(OH)D Level in Athletes. Nutrients 2023; 15:4747. [PMID: 38004144 PMCID: PMC10675819 DOI: 10.3390/nu15224747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 11/08/2023] [Accepted: 11/09/2023] [Indexed: 11/26/2023] Open
Abstract
Vitamin D is crucial to the health and performance of athletes. Although the exact vitamin D requirements for athletes have not been established, maintaining a 25(OH)D level of at least 40 ng/mL is considered beneficial. This randomized controlled intervention study aimed to determine whether an individual loading dose formula for vitamin D supplementation is more effective than standardized supplementation and suitable enough for athletes to meet a target value of 40 ng/mL. In a 10-week supplementation study conducted during the winter months in Germany, 90 athletes with insufficient vitamin D levels (25(OH)D < 30 ng/mL) were randomly assigned to receive either a universal dose of 2000 IU/day of vitamin D or a loading dose of 4000 IU/day, followed by a maintenance dose of 1000 IU/day. The total 25(OH)D concentration was measured from dried blood spots at three time points: at baseline, at the computed date of 40 ng/mL, and after the 10-week period. Additionally, a vitamin-D-specific questionnaire was issued. On the day when 25(OH)D blood concentrations of 40 ng/mL were calculated to prevail, the individualized group had a significantly higher 25(OH)D level than the standardized group (41.1 ± 10.9 ng/mL vs. 32.5 ± 6.4 ng/mL, p < 0.001). This study demonstrated that the examined formula is suitable enough for athletes to achieve a 25(OH)D concentration of 40 ng/mL. This indicates that a personalized approach is more effective than a one-size-fits-all approach in restoring adequate vitamin D levels in athletes.
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Affiliation(s)
- Chiara Tuma
- Institute of Biochemistry/Center of Preventive Doping Research, German Sport University Cologne, 50933 Cologne, Germany (M.T.)
- German Research Centre of Elite Sports (Momentum), German Sport University Cologne, 50933 Cologne, Germany
| | - Arne Schick
- Institute of Biochemistry/Center of Preventive Doping Research, German Sport University Cologne, 50933 Cologne, Germany (M.T.)
| | - Nele Pommerening
- Institute of Biochemistry/Center of Preventive Doping Research, German Sport University Cologne, 50933 Cologne, Germany (M.T.)
| | - Hans Braun
- Institute of Biochemistry/Center of Preventive Doping Research, German Sport University Cologne, 50933 Cologne, Germany (M.T.)
- German Research Centre of Elite Sports (Momentum), German Sport University Cologne, 50933 Cologne, Germany
| | - Mario Thevis
- Institute of Biochemistry/Center of Preventive Doping Research, German Sport University Cologne, 50933 Cologne, Germany (M.T.)
- European Monitoring Center for Emerging Doping Agents, 50933 Cologne, Germany
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16
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Ramanarayanan P, Heine G, Worm M. Vitamin A and vitamin D induced nuclear hormone receptor activation and its impact on B cell differentiation and immunoglobulin production. Immunol Lett 2023; 263:80-86. [PMID: 37774987 DOI: 10.1016/j.imlet.2023.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 08/24/2023] [Accepted: 08/25/2023] [Indexed: 10/01/2023]
Abstract
Vitamin A and vitamin D metabolites are ligands to nuclear receptors - namely RAR, RXR and VDR. The activation of these receptors in human B cells impacts B cell maturation and function. In this review, we discuss how 9-cis retinoic acid (9cRA) and 1,25-dihydroxyvitamin D3 (calcitriol) individually or in conjunction, signal through their nuclear receptors and thereby impact B cell differentiation, immunoglobulin class switching to IgA at the expense of IgE, and also B cell migration and homing. Impact of the vitamin metabolites individually on B cell survival factors are well elucidated, be it the regulation of BAFF and APRIL, the induction of TGF-β or suppression of NF-κB. Very little is known about the impact of 9cRA and calcitriol together on B cells. Recently our group revealed that 9cRA and calcitriol together in the context of the B cell differentiation, induces naïve B cell differentiation into IgA+ plasmablasts, the functional and underlying molecular regulations however require further investigation. In conclusion, the conjunctional impact of these nuclear receptor ligands on B cell functionality is important to better understand B cell dependent clinical outcomes in allergy and autoimmunity. Within this review, we hypothesize that a balance between both vitamins is of utmost importance to provide a robust humoral immune response and a better treatment of disorders characterised by dysregulated immune responses such as IgE-dependent allergy or autoimmunity such as lupus erythematosus.
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Affiliation(s)
| | - Guido Heine
- Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Kiel 24105, Germany
| | - Margitta Worm
- Deutsches Rheuma-Forschung Zentrum (DRFZ), Charitéplatz 1, Berlin 10117, Germany; Department of Dermatology, Venereology and Allergology, Charité University of Medicine, Charitéplatz 1, Berlin 10117, Germany.
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17
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Anastasilakis AD, Polyzos SA, Savvidis M, Anastasilakis DA, Sarridimitriou A, Kumar A, Kalra B, Makras P, Mantzoros CS. Association of activins, follistatins and inhibins with incident hip fracture in women with postmenopausal osteoporosis: a proof of concept, case-control study. Endocrine 2023; 81:573-578. [PMID: 37221430 DOI: 10.1007/s12020-023-03402-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 05/15/2023] [Indexed: 05/25/2023]
Abstract
PURPOSE The activins-follistatins-inhibins (AFI) hormonal system is considered to regulate muscle and bone mass. We aimed to evaluate AFI in postmenopausal women with an incident hip fracture. METHODS In this post-hoc analysis of a hospital based case-control study, we evaluated circulating levels of the AFI system in postmenopausal women with a low-energy hip fracture admitted for fixation compared with postmenopausal women with osteoarthritis scheduled for arthroplasty. RESULTS Circulating levels of follistatin (p = 0.008), FSTL3 (p = 0.013), activin B and AB (both p < 0.001), as well as activin AB/follistatin and activin AB/FSTL3 ratios (p = 0.008 and p = 0.029, respectively) were higher in patients than controls in unadjusted models. Differences for activins B and AB remained after adjustment for age and BMI (p = 0.006 and p = 0.009, respectively) and for FRAX-based risk for hip fracture (p = 0.008 and p = 0.012, respectively) but were lost when 25OHD was added to the regression models. CONCLUSIONS Our data indicate no major changes in the AFI system in postmenopausal women at the time of hip fracture compared to postmenopausal women with osteoarthritis except for higher activin B and AB levels, whose significance, however, was lost when 25OHD was added to the adjustment models. CLINICAL TRIALS Clinical Trials identifier: NCT04206618.
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Affiliation(s)
| | - Stergios A Polyzos
- First Laboratory of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Matthaios Savvidis
- 2nd Orthopedic Department, 424 General Military Hospital, Thessaloniki, Greece
| | - Dimitrios A Anastasilakis
- First Laboratory of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | | | | | - Polyzois Makras
- Department of Endocrinology and Diabetes and Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, Athens, Greece
| | - Christos S Mantzoros
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Boston, VA, USA
- Healthcare System and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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18
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Gao N, Raduka A, Rezaee F. Vitamin D 3 protects against respiratory syncytial virus-induced barrier dysfunction in airway epithelial cells via PKA signaling pathway. Eur J Cell Biol 2023; 102:151336. [PMID: 37354621 PMCID: PMC10773979 DOI: 10.1016/j.ejcb.2023.151336] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 06/19/2023] [Accepted: 06/21/2023] [Indexed: 06/26/2023] Open
Abstract
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection in infants and young children globally and is responsible for hospitalization and mortality in the elderly population. Virus-induced airway epithelial barrier damage is a critical step during RSV infection, and emerging studies suggest that RSV disrupts the tight junctions (TJs) and adherens junctions (AJs) between epithelial cells, increasing the permeability of the airway epithelial barrier. The lack of commercially available vaccines and effective antiviral drugs for RSV emphasizes the need for new management strategies. Vitamin D3 is a promising intervention for viral infection due to its critical role in modulating innate immune responses. However, there is limited evidence on the effect of vitamin D3 on RSV pathogenies. Here, we investigated the impact of vitamin D3 on RSV-induced epithelial barrier dysfunction and the underlying mechanisms. We found that pre-incubation with 1,25(OH)2D3, the active form of vitamin D3, alleviated RSV-induced epithelial barrier disruption in a dose-dependent manner without affecting viability in 16HBE cells. 1,25(OH)2D3 induced minor changes in the protein expression level of TJ/AJ proteins in RSV-infected cells. We observed increased CREB phosphorylation at Ser133 during 1,25(OH)2D3 exposure, indicating that vitamin D3 triggered protein kinase A (PKA) activity in 16HBE. PKA inhibitors modified the restoration of barrier function by 1,25(OH)2D3 in RSV-infected cells, implying that PKA signaling is responsible for the protective effects of vitamin D3 against RSV-induced barrier dysfunction in airway epithelial cells. Our findings suggest vitamin D3 as a prophylactic intervention to protect the respiratory epithelium during RSV infections.
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Affiliation(s)
- Nannan Gao
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Andjela Raduka
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Fariba Rezaee
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA; Center for Pediatric Pulmonary Medicine, Cleveland Clinic Children's, Cleveland, OH, USA.
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19
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Olivencia MA, Villegas-Esguevillas M, Sancho M, Barreira B, Paternoster E, Adão R, Larriba MJ, Cogolludo A, Perez-Vizcaino F. Vitamin D Receptor Deficiency Upregulates Pulmonary Artery Kv7 Channel Activity. Int J Mol Sci 2023; 24:12350. [PMID: 37569725 PMCID: PMC10418734 DOI: 10.3390/ijms241512350] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/26/2023] [Accepted: 07/29/2023] [Indexed: 08/13/2023] Open
Abstract
Recent evidence suggests that vitamin D is involved in the development of pulmonary arterial hypertension (PAH). The aim of this study was to analyze the electrophysiological and contractile properties of pulmonary arteries (PAs) in vitamin D receptor knockout mice (Vdr-/-). PAs were dissected and mounted in a wire myograph. Potassium membrane currents were recorded in freshly isolated PA smooth muscle cells (PASMCs) using the conventional whole-cell configuration of the patch-clamp technique. Potential vitamin D response elements (VDREs) in Kv7 channels coding genes were studied, and their protein expression was analyzed. Vdr-/- mice did not show a pulmonary hypertensive phenotype, as neither right ventricular hypertrophy nor endothelial dysfunction was apparent. However, resistance PA from these mice exhibited increased response to retigabine, a Kv7 activator, compared to controls and heterozygous mice. Furthermore, the current sensitive to XE991, a Kv7 inhibitor, was also higher in PASMCs from knockout mice. A possible VDRE was found in the gene coding for KCNE4, the regulatory subunit of Kv7.4. Accordingly, Vdr-/- mice showed an increased expression of KCNE4 in the lungs, with no changes in Kv7.1 and Kv7.4. These results indicate that the absence of Vdr in mice, as occurred with vitamin D deficient rats, is not sufficient to induce PAH. However, the contribution of Kv7 channel currents to the regulation of PA tone is increased in Vdr-/- mice, resembling animals and humans suffering from PAH.
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Affiliation(s)
- Miguel A Olivencia
- Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain
- Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain
| | - Marta Villegas-Esguevillas
- Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain
- Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain
| | - Maria Sancho
- Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain
- Department of Physiology, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Bianca Barreira
- Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain
- Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain
| | - Elena Paternoster
- Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain
- Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain
| | - Rui Adão
- Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain
- Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain
| | - María Jesús Larriba
- Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28029 Madrid, Spain
- Ciber Cáncer (CIBERONC), 28029 Madrid, Spain
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), 28029 Madrid, Spain
| | - Angel Cogolludo
- Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain
- Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain
| | - Francisco Perez-Vizcaino
- Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain
- Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain
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20
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Ye X, Zhou Q, Ren P, Xiang W, Xiao L. The Synaptic and Circuit Functions of Vitamin D in Neurodevelopment Disorders. Neuropsychiatr Dis Treat 2023; 19:1515-1530. [PMID: 37424961 PMCID: PMC10327924 DOI: 10.2147/ndt.s407731] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 06/07/2023] [Indexed: 07/11/2023] Open
Abstract
Vitamin D deficiency/insufficiency is a public health issue around the world. According to epidemiological studies, low vitamin D levels have been associated with an increased risk of some neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). Animal models reveal that vitamin D has a variety of impacts on the synapses and circuits in the brain. A lack of vitamin D affects the expression of synaptic proteins, as well as the synthesis and metabolism of various neurotransmitters. Depending on where vitamin D receptors (VDRs) are expressed, vitamin D may also regulate certain neuronal circuits through the endocannabinoid signaling, mTOR pathway and oxytocin signaling. While inconsistently, some data suggest that vitamin D supplementation may be able to reduce the core symptoms of ASD and ADHD. This review emphasizes vitamin D's role in the synaptic and circuit mechanisms of neurodevelopmental disorders including ASD and ADHD. Future application of vitamin D in these disorders will depend on both basic research and clinical studies, in order to make the transition from the bench to the bedside.
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Affiliation(s)
- Xiaoshan Ye
- Hainan Women and Children’s Medical Center, School of Pediatrics, Hainan Medical University, Haikou, People’s Republic of China
| | - Qionglin Zhou
- International School of Public Health and One Health, Hainan Medical University, Haikou, People’s Republic of China
| | - Pengcheng Ren
- Hainan Women and Children’s Medical Center, School of Pediatrics, Hainan Medical University, Haikou, People’s Republic of China
- National Health Commission (NHC) Key Laboratory of Control of Tropical Diseases, Hainan Medical University, Haikou, People’s Republic of China
- School of Basic Medicine and Life Science, Hainan Medical University, Haikou, People’s Republic of China
| | - Wei Xiang
- Hainan Women and Children’s Medical Center, School of Pediatrics, Hainan Medical University, Haikou, People’s Republic of China
- National Health Commission (NHC) Key Laboratory of Control of Tropical Diseases, Hainan Medical University, Haikou, People’s Republic of China
| | - Le Xiao
- Hainan Women and Children’s Medical Center, School of Pediatrics, Hainan Medical University, Haikou, People’s Republic of China
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21
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Bollen SE, Bass JJ, Wilkinson DJ, Hewison M, Atherton PJ. The impact of genetic variation within the vitamin D pathway upon skeletal muscle function: A systematic review. J Steroid Biochem Mol Biol 2023; 229:106266. [PMID: 36822332 DOI: 10.1016/j.jsbmb.2023.106266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 01/19/2023] [Accepted: 02/02/2023] [Indexed: 02/23/2023]
Abstract
Studies in vitro have demonstrated a key molecular role for 1,25-dihydroxyvitamin D (1,25D) in skeletal muscle function, with vitamin D-deficiency (low serum 25-hydroxyvitamin D, 25D) being associated with muscle pain and weakness. Despite this, an understanding of the overall role of vitamin D in muscle health (particularly the impact of vitamin D-related genetic variants) has yet to be fully resolved, relative to more well-studied targets such as the skeleton. Thus, we aimed to review existing studies that have investigated relationships between skeletal muscle function and single nucleotide polymorphisms (SNPs) within vitamin D-related genes. A systematic review of papers published between January 2000 and June 2022 on PubMed, EMBASE and Web of Science pertaining to association between functionally relevant vitamin D receptor genetic variants and variants within genes of the vitamin D pathway and skeletal muscle function/outcomes was performed. 21 articles were included in the review for final analysis, of which 20 only studied genetic variation of the VDR gene. Of the included articles, 81 % solely included participants aged ≥ 50 years and of the 9 studies that did not only include White individuals, only 2 included Black participants. Within the vitamin D system, the VDR gene is the primary gene of which associations between polymorphisms and muscle function have been investigated. VDR polymorphisms have been significantly associated with muscle phenotypes in two or more studies. Of note A1012G was significantly associated with higher handgrip strength, but the results for other SNPs were notably variable between studies. While the lack of definitive evidence and study heterogeneity makes it difficult to draw conclusions, the findings of this review highlight a need for improvements with regards to the use of more diverse study populations, i.e., inclusion of Black individuals and other people of colour, and expanding research scope beyond the VDR gene.
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Affiliation(s)
- Shelby E Bollen
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, DE22 3DT UK.
| | - Joseph J Bass
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, DE22 3DT UK
| | - Daniel J Wilkinson
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, DE22 3DT UK
| | - Martin Hewison
- Metabolism and Systems Research, University of Birmingham, Birmingham, UK
| | - Philip J Atherton
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, DE22 3DT UK
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22
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Della Nera G, Sabatino L, Gaggini M, Gorini F, Vassalle C. Vitamin D Determinants, Status, and Antioxidant/Anti-inflammatory-Related Effects in Cardiovascular Risk and Disease: Not the Last Word in the Controversy. Antioxidants (Basel) 2023; 12:antiox12040948. [PMID: 37107323 PMCID: PMC10135791 DOI: 10.3390/antiox12040948] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 04/14/2023] [Accepted: 04/15/2023] [Indexed: 04/29/2023] Open
Abstract
Beyond its key role in calcium homeostasis, vitamin D has been found to significantly affect the cardiovascular (CV) system. In fact, low vitamin D levels have been associated with increased CV risk, as well as increased CV morbidity and mortality. The majority of effects of this molecule are related directly or indirectly to its antioxidative and anti-inflammatory properties. Generally, vitamin D insufficiency is considered for 25-hydroxyvitamin D (25(OH)D) levels between 21-29 ng/mL (corresponding to 52.5-72.5 nmol/L), deficiency as 25(OH)D levels less than 20 ng/mL (<50 nmol/L), and extreme deficiency as 25(OH)D less than 10 ng/mL (<25 nmol/L). However, the definition of an optimal vitamin D status, as defined by 25(OH)D, remains controversial for many extra-bone conditions, including CV disease. In this review, confounding factors affecting the 25(OH)D measurement and status will be discussed. In particular, available evidence on the mechanism and role of vitamin D in relation to CV risk and disease through its antioxidant effect will be reported, also facing the aspect regarding the debate on the minimum blood 25(OH)D level required to ensure optimal CV health.
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23
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Somoza-Moncada MM, Turrubiates-Hernández FJ, Muñoz-Valle JF, Gutiérrez-Brito JA, Díaz-Pérez SA, Aguayo-Arelis A, Hernández-Bello J. Vitamin D in Depression: A Potential Bioactive Agent to Reduce Suicide and Suicide Attempt Risk. Nutrients 2023; 15:1765. [PMID: 37049606 PMCID: PMC10097210 DOI: 10.3390/nu15071765] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 04/01/2023] [Accepted: 04/03/2023] [Indexed: 04/08/2023] Open
Abstract
Suicide is one of the leading causes of death worldwide. According to the World Health Organization (WHO), every year, more than 700 thousand people die from this cause. Therefore, suicide is a public health issue. The complex interaction between different factors causes suicide; however, depression is one of the most frequent factors in people who have attempted suicide. Several studies have reported that vitamin D deficiency may be a relevant risk factor for depression, and vitamin D supplementation has shown promising effects in the adjunctive treatment of this mood disorder. Among the beneficial mechanisms of vitamin D, it has been proposed that it may enhance serotonin synthesis and modulate proinflammatory cytokines since low serotonin levels and systemic inflammation have been associated with depression and suicide. The present narrative review shows the potential pathogenic role of vitamin D deficiency in depression and suicide and the potential benefits of vitamin D supplementation to reduce their risk.
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Affiliation(s)
- María Montserrat Somoza-Moncada
- Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico
| | - Francisco Javier Turrubiates-Hernández
- Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico
| | - José Francisco Muñoz-Valle
- Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico
| | - Jesús Alberto Gutiérrez-Brito
- Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico
| | - Saúl Alberto Díaz-Pérez
- Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico
| | - Adriana Aguayo-Arelis
- Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico
| | - Jorge Hernández-Bello
- Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico
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24
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Marchwicka A, Nowak K, Satyr A, Wołowiec D, Marcinkowska E. Immuno-Stimulating Activity of 1,25-Dihydroxyvitamin D in Blood Cells from Five Healthy People and in Blasts from Five Patients with Leukemias and Pre-Leukemic States. Int J Mol Sci 2023; 24:ijms24076504. [PMID: 37047477 PMCID: PMC10094698 DOI: 10.3390/ijms24076504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 03/22/2023] [Accepted: 03/27/2023] [Indexed: 04/03/2023] Open
Abstract
(1) Hematological malignancies are characterized by an immortalization, uncontrolled proliferation of blood cells and their differentiation block, followed by the loss of function. The primary goal in the treatment of leukemias is the elimination of rapidly proliferating leukemic cells (named blasts). However, chemotherapy, which removes proliferating blasts, also prevents the remaining immune cells from being activated. Acute leukemias affect elderly people, who are often not fit to survive aggressive chemotherapy. Therefore, there is a need of milder treatment, named differentiation therapy, which might simulate the immune system of the patient. 1,25-Dihydroxyvitamin D, or low-calcemic analogs of this compound, were proposed as supporting therapy in acute leukemias. (2) Bone marrow blasts from patients with hematological malignancies, and leukocytes from healthy volunteers were ex vivo exposed to 1,25-dihydroxyvitamin D, and then their genomes and transcriptomes were investigated. (3) Our analysis indicates that 1,25-dihydroxyvitamin D regulates in blood cells predominantly genes involved in immune response, such as CAMP (cathelicidin antimicrobial peptide), CP (ceruloplasmin), CXCL9 (C-X-C motif chemokine ligand 9), CD14 (CD14 molecule) or VMO1 (vitelline membrane outer layer 1 homolog). This concerns blood cells from healthy people, as well as blasts from patients with hematological malignancies. In addition, in one patient, 1,25-dihydroxyvitamin D significantly downregulated transcription of genes responsible for cell division and immortalization. (4) In conclusion, the data presented in this paper suggest that addition of 1,25-dihydroxyvitamin D to the currently available treatments would stimulate immune system, inhibit proliferation and reduce immortal potential of blasts.
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Affiliation(s)
- Aleksandra Marchwicka
- Department of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383 Wrocław, Poland
| | - Kuba Nowak
- Faculty of Mathematics and Computer Science, University of Wrocław, Joliot-Curie 15, 50-383 Wrocław, Poland
| | - Anastasiia Satyr
- Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland
| | - Dariusz Wołowiec
- Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wrocław Medical University, Pasteura 4, 50-367 Wrocław, Poland
| | - Ewa Marcinkowska
- Department of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383 Wrocław, Poland
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25
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Hanai A, Kawabata A, Nakajima K, Masuda K, Urakawa I, Abe M, Yamazaki Y, Fukumoto S. Single-cell RNA sequencing identifies Fgf23-expressing osteocytes in response to 1,25-dihydroxyvitamin D 3 treatment. Front Physiol 2023; 14:1102751. [PMID: 36776964 PMCID: PMC9911654 DOI: 10.3389/fphys.2023.1102751] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 01/16/2023] [Indexed: 01/28/2023] Open
Abstract
Fibroblast growth factor 23 (FGF23), a hormone, mainly produced by osteocytes, regulates phosphate and vitamin D metabolism. By contrast, 1,25-dihydroxyvitamin D3, the active form of vitamin D, has been shown to enhance FGF23 production. While it is likely that osteocytes are heterogenous in terms of gene expression profiles, specific subpopulations of Fgf23-expressing osteocytes have not been identified. Single-cell RNA sequencing (scRNA-seq) technology can characterize the transcriptome of an individual cell. Recently, scRNA-seq has been used for bone tissue analysis. However, owing to technical difficulties associated with isolation of osteocytes, studies using scRNA-seq analysis to characterize FGF23-producing osteocytes are lacking. In this study, we characterized osteocytes secreting FGF23 from murine femurs in response to calcitriol (1,25-dihydroxyvitamin D3) using scRNA-seq. We first detected Dmp1, Mepe, and Phex expression in murine osteocytes by in situ hybridization and used these as marker genes of osteocytes. After decalcification, enzyme digestion, and removal of CD45+ cells, femoral bone cells were subjected to scRNA-seq. We identified cell clusters containing osteocytes using marker gene expression. While Fgf23 expression was observed in some osteocytes isolated from femurs of calcitriol-injected mice, no Fgf23 expression was detected in untreated mice. In addition, the expression of several genes which are known to be changed after 1,25-dihydroxyvitamin D3 treatment such as Ccnd2, Fn1, Igfbp7, Pdgfa, and Timp1 was also affected by calcitriol treatment in Fgf23-expressing osteocytes, but not in those lacking Fgf23 expression, even after calcitriol administration. Furthermore, box-and-whisker plots indicated that Fgf23 expression was observed in osteocytes with higher expression levels of the Fam20c, Dmp1, and Phex genes, whose inactivating mutations have been shown to cause FGF23-related hypophosphatemic diseases. These results indicate that osteocytes are heterogeneous with respect to their responsiveness to 1,25-dihydroxyvitamin D3, and sensitivity to 1,25-dihydroxyvitamin D3 is one of the characteristics of osteocytes with Fgf23 expression. It is likely that there is a subpopulation of osteocytes expressing several genes, including Fgf23, involved in phosphate metabolism.
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Affiliation(s)
- Ayako Hanai
- R&D Division, Kyowa Kirin Co., Ltd., Tokyo, Japan,Department of Endocrinology, Metabolism and Hematology, Tokushima University Graduate School of Medical Sciences, Tokushima, Japan,*Correspondence: Ayako Hanai,
| | | | | | | | | | - Masahiro Abe
- Department of Endocrinology, Metabolism and Hematology, Tokushima University Graduate School of Medical Sciences, Tokushima, Japan
| | | | - Seiji Fukumoto
- Department of Molecular Endocrinology, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan
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26
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Bivona G, Scazzone C, Sasso BL, Giglio RV, Gambino CM, Agnello L, Ciaccio M. Multiple Sclerosis Pathogenesis: Possible Interplay between Vitamin D Status and Epstein Barr Virus Infection. J Integr Neurosci 2023; 22:7. [PMID: 36722238 DOI: 10.31083/j.jin2201007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 08/12/2022] [Accepted: 08/17/2022] [Indexed: 01/11/2023] Open
Affiliation(s)
- Giulia Bivona
- Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy
- Department of Laboratory Medicine, University Hospital "P. Giaccone", 90127 Palermo, Italy
| | - Concetta Scazzone
- Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy
- Department of Laboratory Medicine, University Hospital "P. Giaccone", 90127 Palermo, Italy
| | - Bruna Lo Sasso
- Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy
- Department of Laboratory Medicine, University Hospital "P. Giaccone", 90127 Palermo, Italy
| | - Rosaria Vincenza Giglio
- Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy
- Department of Laboratory Medicine, University Hospital "P. Giaccone", 90127 Palermo, Italy
| | - Caterina Maria Gambino
- Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy
- Department of Laboratory Medicine, University Hospital "P. Giaccone", 90127 Palermo, Italy
| | - Luisa Agnello
- Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy
| | - Marcello Ciaccio
- Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy
- Department of Laboratory Medicine, University Hospital "P. Giaccone", 90127 Palermo, Italy
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27
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In silico assessment of missense point mutations on human cathelicidin LL-37. J Mol Graph Model 2023; 118:108368. [PMID: 36335830 DOI: 10.1016/j.jmgm.2022.108368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 10/11/2022] [Accepted: 10/25/2022] [Indexed: 11/06/2022]
Abstract
Cathelicidin antimicrobial peptides are a diverse family of cationic amphipathic peptides with multiple activities. In humans, cathelicidin LL-37 is one of the main host defense peptides with a remarkable medical and biotechnological potential. Deregulation of LL-37 expression has been associated with inflammatory diseases. However the effects of point mutations driven by single nucleotide polymorphisms (SNPs) on LL-37 are unknown. Here we applied an array of computational tools to investigate the effects of such mutations on LL-37 structure and activity. Due to the fact that, on cathelicidins, the prodomain is more conserved than the mature peptide, the SNP effect predictions were biased and, overall, resulted in neutral effects; and due to the slight changes in physicochemical properties, the antimicrobial predictions indicated the maintenance of such activity. Nonetheless, R07P, R07W, R29Q, R29W mutations reduced the peptide net charge, which in turn could result in less active LL-37 variants. Molecular dynamics data indicated that R07Q and N30Y mutations altered the LL-37 structure, leading to potential deleterious effects. In addition, the helix dipole is altered in G03A, R07P, R07W and L31P mutations, which could also alter the antimicrobial activity. Our results indicated that despite the mutations did not alter the residues from LL-37 active core, they could influence the antimicrobial activity and consequently, could be involved in inflammatory diseases.
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28
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Atcheson RJ, Burne THJ, Dawson PA. Serum sulfate level and Slc13a1 mRNA expression remain unaltered in a mouse model of moderate vitamin D deficiency. Mol Cell Biochem 2022:10.1007/s11010-022-04634-7. [PMID: 36566486 DOI: 10.1007/s11010-022-04634-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 12/05/2022] [Indexed: 12/26/2022]
Abstract
Sulfate is essential for healthy foetal growth and neurodevelopment. The SLC13A1 sulfate transporter is primarily expressed in the kidney where it mediates sulfate reabsorption and maintains circulating sulfate levels. To meet foetal demands, maternal sulfate levels increase by twofold in pregnancy via upregulated SLC13A1 expression. Previous studies found hyposulfataemia and reduced renal Slc13a1 mRNA expression in rodent models with either severe vitamin D deficiency or perturbed vitamin D signalling. Here we investigated a mouse model of moderate vitamin D deficiency. However, serum sulfate level and renal Slc13a1 mRNA expression was not decreased by a moderate reduction in circulating vitamin D level. We confirmed that the mouse Slc13a1 5'-flanking region was upregulated by 1,25(OH)2D3 using luciferase assays in a cultured renal OK cell line. These results support the presence of a functional VDRE in the mouse Slc13a1 but suggests that moderate vitamin D deficiency does not impact on sulfate homeostasis. As sulfate biology is highly conserved between rodents and humans, we proposed that human SLC13A1 would be under similar transcriptional regulation by 1,25(OH)2D3. Using an online prediction tool we identified a putative VDRE in the SLC13A1 5'-flanking region but unlike the mouse Slc13a1 sequence, the human sequence did not confer a significant response to 1,25(OH)2D3 in vitro. Overall, this study suggests that moderate vitamin D deficiency may not alter sulfate homeostasis. This needs to be confirmed in humans, particularly during pregnancy when vitamin D and sulfate levels need to be maintained at high levels for healthy maternal and child outcomes.
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Affiliation(s)
- Ranita J Atcheson
- Mater Research Institute, The University of Queensland, Translational Research Institute, 37 Kent St, Woolloongabba, QLD, 4102, Australia
| | - Thomas H J Burne
- Queensland Brain Institute, The University of Queensland, St. Lucia, QLD, 4072, Australia.,Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD, 4076, Australia
| | - Paul A Dawson
- Mater Research Institute, The University of Queensland, Translational Research Institute, 37 Kent St, Woolloongabba, QLD, 4102, Australia.
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Wells T, Poindexter M, Kweh M, Blakely L, Nelson C. Intramammary 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 treatments differentially increase serum calcium and milk cell gene expression. JDS COMMUNICATIONS 2022; 4:91-96. [PMID: 36974222 PMCID: PMC10039239 DOI: 10.3168/jdsc.2022-0336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 10/05/2022] [Indexed: 12/15/2022]
Abstract
Intramammary 25-hydroxyvitamin D3 (25D) and 1,25-dihydroxyvitamin D3 (1,25D) treatments stimulate immune defenses of the mammary gland. We hypothesized 25D treatment, in contrast to 1,25D, would exert activity in the mammary gland without affecting serum calcium. The objective was to determine the effect of dose and source of intramammary vitamin D treatments on milk somatic cell gene expression and serum calcium. Twenty lactating Holstein cows with somatic cell count <200,000 cells/mL of milk were used for the experiment. Cows were blocked by somatic cell count and randomly assigned to 1 of 5 intramammary treatments (n = 4 cows/treatment): placebo control (CNTRL; 0.4% Tween 20 in phosphate-buffered saline), 100 μg of 25D, 500 μg of 25D, 10 μg of 1,25D, or 50 μg of 1,25D. Treatments were administered in 2 ipsilateral quarters after milking. Blood samples were collected at 0, 12, 24, and 48 h for measurement of Ca and 1,25D. Milk samples were collected from each quarter at 0, 6, 12, 24, and 48 h relative to the start of treatments for measurement of gene expression in milk somatic cells. The 1,25D treatments increased serum concentrations of 1,25D and Ca in a dose-dependent manner with maximum 1,25D and Ca concentrations of 199 ± 6 pg/mL and 2.73 ± 0.04 mM, respectively, observed for 50 μg of 1,25D cows compared with 59 ± 6 pg/mL and 2.54 mM, respectively, for CNTRL cows. The 25D treatments did not affect serum 1,25D and Ca compared with CNTRL. The 25D and 1,25D treatments increased mRNA transcripts for vitamin D 24-hydroxylase (CYP24A1), inducible nitric oxide synthase (NOS2A), and chemokine C-C motif ligand 5 (CCL5) in a dose-dependent manner. The 50 μg of 1,25D treatment resulted in the greatest CYP24A1 expression (303-fold relative to CNTRL) at 6 h but was not different from CNTRL at 24 h. In contrast, CYP24A1 was 57-fold greater for cows that received 500 μg of 25D compared with CNTRL at 24 h. In conclusion, intramammary 25D treatment is effective at regulating gene expression in the mammary gland without systemic effects on serum 1,25D and Ca that occur with intramammary 1,25D treatment.
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Rihal V, Khan H, Kaur A, Singh TG, Abdel-Daim MM. Therapeutic and mechanistic intervention of vitamin D in neuropsychiatric disorders. Psychiatry Res 2022; 317:114782. [PMID: 36049434 DOI: 10.1016/j.psychres.2022.114782] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 08/08/2022] [Accepted: 08/09/2022] [Indexed: 11/19/2022]
Abstract
Vitamin D deficiency is believed to affect between 35 and 55% of the world's population, making it a hidden pandemic. In addition to its role in bone and calcium homeostasis, vitamin D has also been linked in preclinical and clinical research to brain function. These outcomes have also been used for a variety of neuropsychiatric and neurodevelopmental problems. Nevertheless, these individuals are more prone to develop signs of cognitive decline. This review will emphasize the association between vitamin D and neuropsychiatric illnesses such as autism, schizophrenia, depression, and Attention Deficit Hyperactivity Disorder (ADHD). While numerous research show vitamin D's essential role in cognitive function in neuropsychiatric illnesses, it is too early to propose its effect on cognitive symptoms with certainty. It is necessary to conduct additional research into the associations between vitamin D deficiency and cognitive abnormalities, particularly those found in autism, schizophrenia, depression, and ADHD, to develop initiatives that address the pressing need for novel and effective preventative therapeutic strategies.
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Affiliation(s)
- Vivek Rihal
- Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India
| | - Heena Khan
- Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India
| | - Amarjot Kaur
- Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India
| | | | - Mohamed M Abdel-Daim
- Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231 Jeddah 21442, Saudi Arabia; Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt
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31
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Gu Y, Lin S, Morgan JA, Lewis DF, Wang Y. Aberrant endothelial expression of hnRNPC1/C2 and VDR and reduced maternal vitamin D levels in women with preeclampsia. J Steroid Biochem Mol Biol 2022; 222:106155. [PMID: 35868598 DOI: 10.1016/j.jsbmb.2022.106155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 06/17/2022] [Accepted: 07/17/2022] [Indexed: 11/26/2022]
Abstract
Vitamin D deficiency is a widespread health problem globally and vitamin D deficiency/ insufficiency in pregnancy is a risk factor for preeclampsia, a hypertensive disorder in human pregnancy. Vitamin D elicits its biological effects through binding to its receptor VDR. In the present study, we determined maternal vascular expression of VDR and hnRNPC1/C2, a native repressor of VDR, in subcutaneous adipose tissue from women with normal pregnancy and preeclampsia. Maternal antenatal and postnatal vitamin D levels were measured. We found that hnRNPC1/C2 expression was markedly increased, while VDR expression was markedly reduced, in maternal vessel endothelium and smooth muscle cells from women with preeclampsia compared to that from normal pregnant controls. Reduced VDR expression was relevant to low maternal antenatal and postnatal vitamin D levels in women with preeclampsia. Using human umbilical vein endothelial cells (HUVECs) as an endothelial model, we further investigated the role of hnRNPC1/C2-mediated VDR expression in endothelial cells, and tested effect of hnRNPC1/C2 inhibition on endothelial response to bioactive vitamin D, 1,25(OH)2D3. Our results showed that inhibition of hnRNPC1/C2 by hnRNPC1/C2 siRNA resulted in not only an increase in endothelial VDR expression, but further improved endothelial response to 1,25(OH)2D3. These findings indicate that aberrant hnRNPC1/C2 expression may contribute to reduced vascular expression of VDR in women with preeclampsia and suggest that hnRNPC1/C2 could be a target for improving vascular endothelial cell response to vitamin D.
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Affiliation(s)
- Yang Gu
- Department of Obstetrics and Gynecology, LSUHSC, Shreveport, LA 71130, USA
| | - Shuai Lin
- Department of Obstetrics and Gynecology, LSUHSC, Shreveport, LA 71130, USA; Department of Obstetrics and Gynecology, First Affiliated Hospital, Harbin Medical University, Harbin 150086, China
| | - John A Morgan
- Department of Obstetrics and Gynecology, LSUHSC, Shreveport, LA 71130, USA
| | - David F Lewis
- Department of Obstetrics and Gynecology, LSUHSC, Shreveport, LA 71130, USA
| | - Yuping Wang
- Department of Obstetrics and Gynecology, LSUHSC, Shreveport, LA 71130, USA.
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Araújo TSS, Santos CS, Soares JKB, Freitas JCR. Vitamin D: a potentially important secosteroid for coping with COVID-19. AN ACAD BRAS CIENC 2022; 94:e20201545. [PMID: 36000671 DOI: 10.1590/0001-3765202220201545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 01/28/2021] [Indexed: 12/15/2022] Open
Abstract
COVID-19 is a disease that has caused a high number of deaths in the world, and despite being controlled, it requires attention and the search for new quick and economical therapeutic strategies. In this sense, vitamin D stands out, an immunomodulator that has shown beneficial effects in decreasing the risk and severity of acute respiratory tract infections, including COVID-19. Therefore, this review presents a number of experimental, observational and clinical studies on the importance of vitamin D against viral infections with an emphasis on COVID-19, highlighting the relationship between vitamin D, Renin-Angiotensin System and cytokine storms with decreased inflammatory lesions in patients with COVID-19. In addition, aspects of pathophysiology, metabolism, risk factors, sources and recommendations of vitamin D are described. We conclude that vitamin D plays a protective role against inflammatory lesions and can decrease the risk of infections and the severity of COVID-19. Therefore, it is essential to maintain adequate levels of vitamin D to avoid complications related to its deficiency.
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Affiliation(s)
- Thayanne S S Araújo
- Universidade Federal de Campina Grande, Centro de Educação e Saúde, Rua Professora Maria Anita Furtado Coelho, s/n, Sítio Olho D'água da Bica, 58175-000 Cuité, PB, Brazil
| | - Cosme S Santos
- Universidade Federal Rural de Pernambuco, Departamento de Química, Rua Dom Manoel de Medeiros, s/n, 52171-900 Recife, PE, Brazil
| | - Juliana K B Soares
- Universidade Federal de Campina Grande, Centro de Educação e Saúde, Rua Professora Maria Anita Furtado Coelho, s/n, Sítio Olho D'água da Bica, 58175-000 Cuité, PB, Brazil
| | - Juliano C R Freitas
- Universidade Federal de Campina Grande, Centro de Educação e Saúde, Rua Professora Maria Anita Furtado Coelho, s/n, Sítio Olho D'água da Bica, 58175-000 Cuité, PB, Brazil.,Universidade Federal Rural de Pernambuco, Departamento de Química, Rua Dom Manoel de Medeiros, s/n, 52171-900 Recife, PE, Brazil
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Hasan M, Oster M, Reyer H, Ponsuksili S, Murani E, Wolf P, Fischer DC, Wimmers K. Tissue-Wide Expression of Genes Related to Vitamin D Metabolism and FGF23 Signaling following Variable Phosphorus Intake in Pigs. Metabolites 2022; 12:metabo12080729. [PMID: 36005601 PMCID: PMC9413461 DOI: 10.3390/metabo12080729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/01/2022] [Accepted: 08/02/2022] [Indexed: 11/16/2022] Open
Abstract
Calcium (Ca) and phosphorus (P) homeostasis is maintained by several regulators, including vitamin D and fibroblast growth factor 23 (FGF23), and their tissue-specific activation and signaling cascades. In this study, the tissue-wide expression of key genes linked to vitamin D metabolism (CYP2R1, CYP27A1, CYP27B1, CYP24A1, GC, VDR) and FGF23 signaling (FGF23, FGFR1-4, KL) were investigated in pigs fed conventional (trial 1) and divergent P diets (trial 2). The tissue set comprised kidney, liver, bone, lung, aorta, and gastrointestinal tract sections. Expression patterns revealed that non-renal tissues and cells (NRTC) express genes to form active vitamin D [1,25(OH)2D3] according to site-specific requirements. A low P diet resulted in higher serum calcitriol and increased CYP24A1 expression in the small intestine, indicating local suppression of vitamin D signaling. A high P diet prompted increased mRNA abundances of CYP27B1 for local vitamin D synthesis, specifically in bone. For FGF23 signaling, analyses revealed ubiquitous expression of FGFR1-4, whereas KL was expressed in a tissue-specific manner. Dietary P supply did not affect skeletal FGF23; however, FGFR4 and KL showed increased expression in bone at high P supply, suggesting regulation to balance mineralization. Specific NRTC responses influence vitamin D metabolism and P homeostasis, which should be considered for a thrifty but healthy P supply.
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Affiliation(s)
- Maruf Hasan
- Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
| | - Michael Oster
- Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
| | - Henry Reyer
- Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
| | - Siriluck Ponsuksili
- Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
| | - Eduard Murani
- Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
| | - Petra Wolf
- Faculty of Agricultural and Environmental Sciences, University of Rostock, Justus-von-Liebig-Weg 6b, 18059 Rostock, Germany
| | - Dagmar-Christiane Fischer
- Department of Pediatrics, Rostock University Hospital, Ernst-Heydemann-Str. 8, 18057 Rostock, Germany
| | - Klaus Wimmers
- Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
- Faculty of Agricultural and Environmental Sciences, University of Rostock, Justus-von-Liebig-Weg 6b, 18059 Rostock, Germany
- Correspondence: ; Tel.: +49-38208-68600
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Kim GM, Jeon GH. Correlation between Serum 25-Hydroxyvitamin D Level and Depression among Korean Women with Secondary Amenorrhea: A Cross-Sectional Observational Study. Nutrients 2022; 14:nu14142835. [PMID: 35889792 PMCID: PMC9315875 DOI: 10.3390/nu14142835] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 07/02/2022] [Accepted: 07/07/2022] [Indexed: 11/16/2022] Open
Abstract
Vitamin D deficiency is considered a major public health problem worldwide and has been reported as having an association with depression. However, studies on the association between vitamin D deficiency and depressive symptoms in secondary amenorrhea (SA) patients are still scarce. This study examined the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and depressive symptoms among Korean women with SA. In this cross-sectional observational study, 78 patients with SA were initially recruited. Clinical and biochemical parameters, including serum 25(OH)D level, were measured. Data from 63 SA patients who met the study inclusion criteria and completed psychiatric assessments were finally analyzed. We analyzed their association with depression using a hierarchical regression model. The average serum 25(OH)D level was 34.40 ± 24.02 ng/mL, and 41.3% of the women with SA were vitamin D-deficient (<20 ng/mL). The total score of the Korean version of the Hamilton Depression Rating Scale (K-HDRS) was negatively related to serum 25(OH)D levels, free testosterone, and serum anti-Müllerian hormone (AMH) after adjusting for age and BMI (r = −0.450, p < 0.001; r = −0.258, p = 0.045; and r = −0.339, p = 0.006, respectively). Serum 25(OH)D levels and AMH levels were the most powerful predictors of depressive severity when using the K-HDRS in SA patients (β = −0.39, p < 0.005; β = −0.42, p < 0.005, respectively). This study showed that low serum 25(OH)D levels were associated with the severity of depressive symptoms in SA patients. This observation suggests that the evaluation of vitamin D deficiency for the risk of depression may be necessary in patients with SA.
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Affiliation(s)
- Gyung-Mee Kim
- Department of Psychiatry, Haeundae Paik Hospital, Inje University School of Medicine, Busan 48108, Korea;
| | - Gyun-Ho Jeon
- Department of Obstetrics and Gynecology, Haeundae Paik Hospital, Inje University School of Medicine, Busan 48108, Korea
- Correspondence: ; Tel.: +82-51-797-2020
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Gombash SE, Lee PW, Sawdai E, Lovett-Racke AE. Vitamin D as a Risk Factor for Multiple Sclerosis: Immunoregulatory or Neuroprotective? Front Neurol 2022; 13:796933. [PMID: 35651353 PMCID: PMC9149265 DOI: 10.3389/fneur.2022.796933] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 04/13/2022] [Indexed: 12/18/2022] Open
Abstract
Vitamin D insufficiency during childhood has been linked to the development of multiple sclerosis (MS), typically an adult-onset inflammatory demyelinating disease of the central nervous system (CNS). Since vitamin D was known to have immunoregulatory properties on both innate and adaptive immunity, it was hypothesized that low vitamin D resulted in aberrant immune responses and the development of MS. However, vitamin D receptors are present on many cell types, including neurons, oligodendrocytes, astrocytes and microglia, and vitamin D has profound effects on development and function of the CNS. This leads to the possibility that low vitamin D may alter the CNS in a manner that makes it vulnerable to inflammation and the development of MS. This review analysis the role of vitamin D in the immune and nervous system, and how vitamin D insufficiency in children may contribute to the development of MS.
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Affiliation(s)
- Sara E Gombash
- Department of Neuroscience, The Ohio State University, Columbus, OH, United States
| | - Priscilla W Lee
- Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, United States
| | - Elizabeth Sawdai
- Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, United States
| | - Amy E Lovett-Racke
- Department of Neuroscience, The Ohio State University, Columbus, OH, United States.,Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, United States
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Phillips EA, Hendricks N, Bucher M, Maloyan A. Vitamin D Supplementation Improves Mitochondrial Function and Reduces Inflammation in Placentae of Obese Women. Front Endocrinol (Lausanne) 2022; 13:893848. [PMID: 35712242 PMCID: PMC9195071 DOI: 10.3389/fendo.2022.893848] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 04/25/2022] [Indexed: 11/15/2022] Open
Abstract
Background About 30% of women entering pregnancy in the US are obese. We have previously reported mitochondrial dysregulation and increased inflammation in the placentae of obese women. Vitamin D (VitD) is a major player in calcium uptake and was shown to modulate mitochondrial respiration and the immune/inflammation system. Studies show decreased VitD levels in obese individuals; however, the effect of maternal obesity on VitD metabolism and its association with placental function remains understudied. Methods Maternal and cord blood plasma and placental samples were collected upon C-section from normal-weight (NW, body mass index [BMI]<25) and obese (OB, BMI>30) women with uncomplicated pregnancies at term. We measured 25(OH)D3 (calcidiol) levels in maternal and cord blood plasma using ELISA. We assessed the expression of CYP27B1, an activator of calcidiol, and Vitamin D receptor (VDR) in placentae from NW and OB, and women with gestational diabetes and preeclampsia. In addition, we examined the effects of VitD supplementation on mitochondrial function and inflammation in trophoblasts from NW and OB, using the Seahorse Bioanalyzer and Western blot, respectively. Results Vitamin D levels in blood from OB but not NW women and in cord blood from babies born to NW and OB women showed a significant inverse correlation with maternal pre-pregnancy BMI (r=-0.50, p<0.1 and r=-0.55, p=0.004 respectively). Cord plasma VitD levels showed a positive correlation with placental efficiency, i.e., the ratio between fetal and placental weight, as well as with maternal blood VitD levels (r=0.69 and 0.83 respectively, p<0.00). While we found no changes in CYP27B1 in OB vs. NW women, VDR expression were decreased by 50% (p<0.03) independent of fetal sex. No changes in VDR expression relative to BMI-matched controls were observed in the placentae of women with gestational diabetes or preeclampsia. Cytotrophoblasts isolated from placentae of OB women showed a dose-dependent increase in VDR expression after 24-hour treatment with calcitriol (10 nM and 100 nM), an active form of VitD. Trophoblasts isolated from OB women and treated with calcitriol improved mitochondrial respiration (p<0.05). We also found a two-fold increase in expression of the NLRP3 inflammasome and the pro-inflammatory cytokine IL-18 in trophoblasts isolated from placentae of OB women (p<0.05), with IL-18 expression being reversed by calcitriol treatment (100 nM). Conclusions We show that VitD deficiency is at least partially responsible for mitochondrial dysfunction and increased inflammation in the placentae of obese women. Vitamin D supplementation could be beneficial in improving placental dysfunction seen in obese women.
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Affiliation(s)
- Elysse A. Phillips
- Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, United States
| | - Nora Hendricks
- Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, United States
| | - Matthew Bucher
- Department of OB/GYN, Oregon Health and Science University, Portland, OR, United States
| | - Alina Maloyan
- Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, United States
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Brzeziański M, Migdalska-Sęk M, Czechowska A, Radzimiński Ł, Jastrzębski Z, Brzeziańska-Lasota E, Sewerynek E. Correlation between the Positive Effect of Vitamin D Supplementation and Physical Performance in Young Male Soccer Players. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:5138. [PMID: 35564532 PMCID: PMC9101676 DOI: 10.3390/ijerph19095138] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/17/2022] [Accepted: 04/21/2022] [Indexed: 02/01/2023]
Abstract
The aim of this study was to determine whether supplementation with vitamin D during eight weeks of high-intensity training influences muscle power and aerobic performance in young soccer players. A total of 25 athletes were divided into two groups: the supplemented group (GS; n = 12; vitamin D 20,000 IU, twice a week) and the non-supplemented group (GN; n = 13). A set of measurements, including sprint tests, explosive power test, maximal oxygen uptake (VO2max), and serum 25(OH)D concentration, were obtained before (T1) and after (T2) the intervention. A significant group x time interaction was found in the 25(OH)D serum levels (p = 0.002; ES = 0.36, large). A significant improvement in VO2max was found in the TG (p = 0.0004) and the GS (p = 0.031). Moreover, a positive correlation between 25(OH)D and VO2max (R = 0.4192, p = 0.0024) was calculated. The explosive power tests revealed insignificant time interactions in the average 10-jump height and average 10-jump power (p = 0.07, ES = 0.13; p = 0.10, ES = 0.11, respectively). A statistically insignificant trend was observed only in the group-by-time interaction for the sprint of 10 m (p = 0.05; ES = 0.15, large). The present study provides evidence that vitamin D supplementation has a positive but trivial impact on the explosive power and locomotor skills of young soccer players, but could significantly affect their aerobic performance.
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Affiliation(s)
- Michał Brzeziański
- Department of Endocrine Disorders and Bone Metabolism, Medical University of Lodz, 90-752 Lodz, Poland; (M.B.); (E.S.)
- Academic Laboratory of Three-Dimensional Anthropometry, Medical University of Lodz, 92-213 Lodz, Poland
| | - Monika Migdalska-Sęk
- Department of Biomedicine and Genetics, Medical University of Lodz, 92-213 Lodz, Poland;
| | - Aleksandra Czechowska
- Academic Laboratory of Movement and Human Physical Performance, Medical University of Lodz, 92-213 Lodz, Poland
| | - Łukasz Radzimiński
- Department of Physiology and Biochemistry, Gdansk University of Physical Education and Sport, 80-336 Gdansk, Poland; (Ł.R.); (Z.J.)
| | - Zbigniew Jastrzębski
- Department of Physiology and Biochemistry, Gdansk University of Physical Education and Sport, 80-336 Gdansk, Poland; (Ł.R.); (Z.J.)
| | - Ewa Brzeziańska-Lasota
- Department of Biomedicine and Genetics, Medical University of Lodz, 92-213 Lodz, Poland;
| | - Ewa Sewerynek
- Department of Endocrine Disorders and Bone Metabolism, Medical University of Lodz, 90-752 Lodz, Poland; (M.B.); (E.S.)
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Abstract
Vitamin D, best known for its role in skeletal health, has emerged as a key regulator of innate immune responses to microbial threat. In immune cells such as macrophages, expression of CYP27B1, the 25-hydroxyvitamin D 1α-hydroxylase, is induced by immune-specific inputs, leading to local production of hormonal 1,25-dihydroxyvitamin D (1,25D) at sites of infection, which in turn directly induces the expression of genes encoding antimicrobial peptides. Vitamin D signaling is active upstream and downstream of pattern recognition receptors, which promote front-line innate immune responses. Moreover, 1,25D stimulates autophagy, which has emerged as a mechanism critical for control of intracellular pathogens such as M. tuberculosis. Strong laboratory and epidemiological evidence links vitamin D deficiency to increased rates of conditions such as dental caries, as well as inflammatory bowel diseases arising from dysregulation of innate immune handling intestinal flora. 1,25D is also active in signaling cascades that promote antiviral innate immunity; 1,25D-induced expression of the antimicrobial peptide CAMP/LL37, originally characterized for its antibacterial properties, is a key component of antiviral responses. Poor vitamin D status is associated with greater susceptibility to viral infections, including those of the respiratory tract. Although the severity of the COVID-19 pandemic has been alleviated in some areas by the arrival of vaccines, it remains important to identify therapeutic interventions that reduce disease severity and mortality, and accelerate recovery. This review outlines of our current knowledge of the mechanisms of action of vitamin D signaling in the innate immune system. It also provides an assessment of the therapeutic potential of vitamin D supplementation in infectious diseases, including an up-to-date analysis of the putative benefits of vitamin D supplementation in the ongoing COVID-19 crisis.
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Affiliation(s)
- Aiten Ismailova
- Departments of Physiology, McGill University, Montreal, Qc, Canada
| | - John H White
- Departments of Physiology, McGill University, Montreal, Qc, Canada.
- Departments of Medicine, McGill University, Montreal, Qc, Canada.
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Tao E, Zhu Z, Hu C, Long G, Chen B, Guo R, Fang M, Jiang M. Potential Roles of Enterochromaffin Cells in Early Life Stress-Induced Irritable Bowel Syndrome. Front Cell Neurosci 2022; 16:837166. [PMID: 35370559 PMCID: PMC8964523 DOI: 10.3389/fncel.2022.837166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 02/09/2022] [Indexed: 12/04/2022] Open
Abstract
Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, also known as disorders of the gut–brain interaction; however, the pathophysiology of IBS remains unclear. Early life stress (ELS) is one of the most common risk factors for IBS development. However, the molecular mechanisms by which ELS induces IBS remain unclear. Enterochromaffin cells (ECs), as a prime source of peripheral serotonin (5-HT), play a pivotal role in intestinal motility, secretion, proinflammatory and anti-inflammatory effects, and visceral sensation. ECs can sense various stimuli and microbiota metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids. ECs can sense the luminal environment and transmit signals to the brain via exogenous vagal and spinal nerve afferents. Increasing evidence suggests that an ECs-5-HT signaling imbalance plays a crucial role in the pathogenesis of ELS-induced IBS. A recent study using a maternal separation (MS) animal model mimicking ELS showed that MS induced expansion of intestinal stem cells and their differentiation toward secretory lineages, including ECs, leading to ECs hyperplasia, increased 5-HT production, and visceral hyperalgesia. This suggests that ELS-induced IBS may be associated with increased ECs-5-HT signaling. Furthermore, ECs are closely related to corticotropin-releasing hormone, mast cells, neuron growth factor, bile acids, and SCFAs, all of which contribute to the pathogenesis of IBS. Collectively, ECs may play a role in the pathogenesis of ELS-induced IBS. Therefore, this review summarizes the physiological function of ECs and focuses on their potential role in the pathogenesis of IBS based on clinical and pre-clinical evidence.
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Affiliation(s)
- Enfu Tao
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
- Wenling Maternal and Child Health Care Hospital, Wenling, China
| | - Zhenya Zhu
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Chenmin Hu
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Gao Long
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Bo Chen
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Rui Guo
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Marong Fang
- Institute of Neuroscience and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Mizu Jiang
- Department of Gastroenterology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
- *Correspondence: Mizu Jiang,
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Zhou Y, Li S. Meta-Analysis of Vitamin D Receptor Gene Polymorphisms in Childhood Asthma. Front Pediatr 2022; 10:843691. [PMID: 35433530 PMCID: PMC9010509 DOI: 10.3389/fped.2022.843691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Accepted: 02/23/2022] [Indexed: 11/21/2022] Open
Abstract
We conducted the systematic review to investigate the potential relationship between the vitamin polymorphisms of D receptor (VDR) gene and childhood asthma. Relevant studies researching on VDR polymorphisms and asthma susceptibility were searched throughout Embase, PubMed, China Science and technology journal database (CQVIP), etc. till 12 April, 2021. We calculated the pooled odds ratios (OR) and its 95% confidence interval (CI) using RevMan 5.3 software and Stata 11.0. FokI (rs2228570) could significantly affect childhood asthma risk across co dominant model (Ff vs. FF: OR (95%CI) = 0.82 (0.65, 1.02), P = 0.071) and dominant model (ff+Ff vs. FF: OR (95%CI) = 0.77 (0.63, 0.95), P = 0.016), especially among Caucasians in additive model (f vs. F: OR (95%CI) = 0.63 (0.43, 0.92), P = 0.015) and dominant model (ff+Ff vs. FF: OR (95%CI) = 0.67 (0.51, 0.88), P = 0.004). TaqI (rs731236) was significantly related with childhood asthma in additive model (t vs. T: OR (95%CI) = 0.45 (0.23, 0.89), P = 0.022), co dominant model (Tt vs. TT: OR (95%CI) = 0.36 (0.17, 0.77), P = 0.009), and dominant model (tt+Tt vs. TT: OR (95%CI) = 0.36 (0.15, 0.87), P = 0.024) among Asian, as well as population-based subgroup in co dominant model (Tt vs. TT: OR (95%CI) = 0.53 (0.31, 0.94), P = 0.029). However, no evidence supported the role of ApaI (rs7975232) and BsmI (rs1544410) polymorphisms in childhood asthma. FokI and TaqI polymorphisms were found to be related with the susceptibility of childhood asthma. However, it seems that ApaI and BsmI polymorphisms are not related with childhood asthma susceptibility.
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Affiliation(s)
- Yong Zhou
- Department of Pediatrics, Yancheng Maternal and Child Health Care Hospital, Yancheng, China
| | - Sheng Li
- Department of Pediatrics, Yancheng Maternal and Child Health Care Hospital, Yancheng, China
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Jarosz AC, Noori D, Zeitoun T, Garcia-Bailo B, El-Sohemy A. Variation in the vitamin D receptor gene, plasma 25-hydroxyvitamin D, and risk of premenstrual symptoms. GENES & NUTRITION 2021; 16:15. [PMID: 34551710 PMCID: PMC8459465 DOI: 10.1186/s12263-021-00696-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 09/06/2021] [Indexed: 11/10/2022]
Abstract
Background Vitamin D status has been associated with the presence and severity of several premenstrual symptoms (PMSx) in some, but not all studies. Inconsistencies among findings may be explained by unaccounted genetic variation in the vitamin D receptor (VDR). Objective To determine whether associations between vitamin D status and individual PMSx are influenced by VDR genotype. Methods Seven hundred sixteen women aged 20-29 years old from the Toronto Nutrigenomics and Health study provided plasma samples and completed a questionnaire on the presence and severity of 15 common PMSx. Plasma 25-hydroxyvitamin D (25(OH)D) concentration was measured and participants were categorized into sufficient (≥ 50 nmol/L) and insufficient (< 50 nmol/L) vitamin D status groups. DNA was obtained from blood samples to genotype for a common VDR single nucleotide variant, rs796858. Using logistic regression, odds of experiencing PMSx were compared between vitamin D-sufficient and insufficient women, stratified by genotype. Results Among CC homozygotes, insufficient vitamin D status was associated with higher odds of experiencing premenstrual fatigue (OR, 2.53; 95% CI, 1.40, 4.56) and nausea (OR, 2.44; 95% CI, 1.00, 5.95). Among TT homozygotes, insufficient vitamin D status was associated with lower odds of experiencing fatigue (OR, 0.44; 95% CI, 0.20, 0.97) and increased appetite (OR, 0.48; 95% CI, 0.22, 1.04). Insufficient vitamin D status was associated with higher odds of increased appetite in women with the CT genotype (OR, 1.78; 95% CI, 1.03, 3.07). VDR genotype modified the association between vitamin D status and the following PMSx: increased appetite (interaction p = 0.027), fatigue (interaction p = 0.016), and nausea (interaction p = 0.039). Conclusion We found evidence that VDR genotype may modify the association between 25(OH)D and some PMSx. Insufficient 25(OH)D was associated with a higher risk of premenstrual fatigue in those with the CC genotype, but lower risk in those with the TT genotype. Supplementary Information The online version contains supplementary material available at 10.1186/s12263-021-00696-2.
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Wei YX, Liu BP, Qiu HM, Zhang JY, Wang XT, Jia CX. Effects of vitamin D-related gene polymorphisms on attempted suicide. Psychiatr Genet 2021; 31:230-238. [PMID: 34412081 DOI: 10.1097/ypg.0000000000000295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVE Emerging evidence suggests that vitamin D might protect from attempted suicide. The study aimed to investigate the associations between single-nucleotide polymorphisms (SNPs) related to vitamin D levels identified in a large genome-wide association study and attempted suicide in rural China. METHODS This 1:1 matched case-control study included altogether 510 suicide attempters and 510 community controls. Genotypes of four target SNPs (DHCR7-rs12785878, CYP2R1-rs10741657, GC-rs2282679, and CYP24A1-rs6013897) were determined, and a genetic risk score (GRS) was constructed to evaluate the combined effect of them. Demographic and psychological information was acquired through face-to-face interviews. RESULTS The A allele of CYP24A1-rs6013897 was significantly associated with attempted suicide (OR = 1.27, 95% CI, 1.03-1.58, P = 0.029), even after adjusting for demographic and psychological confounders (adjusted OR = 1.53, 95% CI, 1.01-2.30, P = 0.043). The GRS analyses revealed a significantly higher risk of attempted suicide with a greater number of low vitamin D alleles (adjusted OR = 1.33, 95% CI, 1.13-1.58, P < 0.001). Subgroup analyses stratified by sex indicated that the genetic associations were only significant among males with adjusted ORs of 3.77 (95% CI, 1.56-9.10) for the A allele of rs6013897 and 2.04 (95% CI, 1.32-3.17) for GRS. CONCLUSIONS Our findings identity CYP24A1-rs6013897 as a potential biomarker for attempted suicide and indicate that a genetic predisposition to lower vitamin D levels may contribute to attempted suicide. It suggests the possibility that vitamin D may have the preventive potential for attempted suicide.
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Affiliation(s)
- Yan-Xin Wei
- Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University
- Shandong University Center for Suicide Prevention Research
| | - Bao-Peng Liu
- Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University
- Shandong University Center for Suicide Prevention Research
| | - Hui-Min Qiu
- Department of Psychology, Shandong Provincial Center for Mental Health
| | - Ji-Yu Zhang
- Department of Business Management, Shandong Provincial Center for Disease Control and Prevention, Jinan, Shandong, China
| | - Xin-Ting Wang
- Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University
- Shandong University Center for Suicide Prevention Research
| | - Cun-Xian Jia
- Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University
- Shandong University Center for Suicide Prevention Research
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Alliband KH, Kozhevnikova SV, Parr T, Jethwa PH, Brameld JM. In vitro Effects of Biologically Active Vitamin D on Myogenesis: A Systematic Review. Front Physiol 2021; 12:736708. [PMID: 34566700 PMCID: PMC8458760 DOI: 10.3389/fphys.2021.736708] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 08/06/2021] [Indexed: 11/13/2022] Open
Abstract
Vitamin D (VD) deficiency is associated with muscle weakness. A reduction in the incidence of falls in the elderly following VD supplementation and identification of the VD receptor within muscle cells suggests a direct effect of VD on muscle, but little is known about the underlying mechanisms. Here we systematically searched the literature to identify effects of active VD [1,25(OH)2D3] on skeletal muscle myogenesis in vitro, with no restriction on year of publication. Eligibility was assessed by strict inclusion/exclusion criteria and agreed by two independent investigators. Twelve relevant pa-pers were identified using four different cell types (C2C12, primary mouse satellite cells, primary chick myoblasts, and primary human myoblasts) and a range of myogenic markers (myoD, myogenin, creatine kinase, myosin heavy chain, and myotube size). A clear inhibitory effect of 1,25(OH)2D3 on proliferation was reported, while the effects on the different stages of differentiation were less consistent probably due to variation in cell type, time points and doses of 1,25(OH)2D3 used. However, myotube size was consistently increased by 1,25(OH)2D3. Overall, the evidence suggests that 1,25(OH)2D3 inhibits proliferation and promotes differentiation of myoblasts, but future studies should use time courses to gain a clearer understanding.
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Affiliation(s)
- Kathryn H Alliband
- Division of Food Nutrition and Dietetics, School of Biosciences, University of Nottingham Sutton Bonington Campus, Loughborough, United Kingdom
| | - Sofia V Kozhevnikova
- Division of Food Nutrition and Dietetics, School of Biosciences, University of Nottingham Sutton Bonington Campus, Loughborough, United Kingdom
| | - Tim Parr
- Division of Food Nutrition and Dietetics, School of Biosciences, University of Nottingham Sutton Bonington Campus, Loughborough, United Kingdom
| | - Preeti H Jethwa
- Division of Food Nutrition and Dietetics, School of Biosciences, University of Nottingham Sutton Bonington Campus, Loughborough, United Kingdom
| | - John M Brameld
- Division of Food Nutrition and Dietetics, School of Biosciences, University of Nottingham Sutton Bonington Campus, Loughborough, United Kingdom
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Zech LD, Scherf-Clavel M, Daniels C, Schwab M, Deckert J, Unterecker S, Herr AS. Patients with higher vitamin D levels show stronger improvement of self-reported depressive symptoms in psychogeriatric day-care setting. J Neural Transm (Vienna) 2021; 128:1233-1238. [PMID: 34304320 PMCID: PMC8321983 DOI: 10.1007/s00702-021-02385-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 07/14/2021] [Indexed: 02/07/2023]
Abstract
Depression is a common psychiatric disorder among geriatric patients that decreases the quality of life and increases morbidity and mortality. Vitamin D as a neuro-steroid hormone might play a role in the onset and treatment of depression. In the present study, the association between depressive symptoms and vitamin D concentration in serum was evaluated. 140 patients of a psychogeriatric day-care unit were included. The geriatric depression scale (GDS) and the Hamilton depression rating scale (HDRS) were assessed at the beginning and end of treatment, GDS scores additionally 6 weeks after discharge from the day-care unit. Vitamin D levels were measured at the beginning of the treatment, routinely. Patients with levels below 30 µg/L were treated with 1000 IU vitamin D per day. There was no association between the severity of depressive symptoms and the concentration of vitamin D at the beginning of the treatment. Patients with higher vitamin D levels showed a stronger decline of depressive symptoms measured by the GDS during their stay in the day-care unit. We provide evidence that vitamin D serum levels might influence antidepressant therapy response in a geriatric population. Prospective studies are necessary to determine which patients may profit from add-on vitamin D therapy.
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Affiliation(s)
- Linda D Zech
- Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany
| | - Maike Scherf-Clavel
- Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany
| | - Christine Daniels
- Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany
| | - Michael Schwab
- Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany
| | - Jürgen Deckert
- Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany
| | - Stefan Unterecker
- Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany.
| | - Alexandra S Herr
- Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany
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Proal AD, VanElzakker MB. Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms. Front Microbiol 2021; 12:698169. [PMID: 34248921 PMCID: PMC8260991 DOI: 10.3389/fmicb.2021.698169] [Citation(s) in RCA: 526] [Impact Index Per Article: 131.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 05/17/2021] [Indexed: 12/23/2022] Open
Abstract
The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of coronavirus disease 2019 (COVID-19). Across the globe, a subset of patients who sustain an acute SARS-CoV-2 infection are developing a wide range of persistent symptoms that do not resolve over the course of many months. These patients are being given the diagnosis Long COVID or Post-acute sequelae of COVID-19 (PASC). It is likely that individual patients with a PASC diagnosis have different underlying biological factors driving their symptoms, none of which are mutually exclusive. This paper details mechanisms by which RNA viruses beyond just SARS-CoV-2 have be connected to long-term health consequences. It also reviews literature on acute COVID-19 and other virus-initiated chronic syndromes such as post-Ebola syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to discuss different scenarios for PASC symptom development. Potential contributors to PASC symptoms include consequences from acute SARS-CoV-2 injury to one or multiple organs, persistent reservoirs of SARS-CoV-2 in certain tissues, re-activation of neurotrophic pathogens such as herpesviruses under conditions of COVID-19 immune dysregulation, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage care for specific patients with the diagnosis.
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Affiliation(s)
- Amy D. Proal
- PolyBio Research Foundation, Kenmore, WA, United States
| | - Michael B. VanElzakker
- PolyBio Research Foundation, Kenmore, WA, United States
- Division of Neurotherapeutics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
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Żychowska M, Rola R, Borkowska A, Tomczyk M, Kortas J, Anczykowska K, Pilis K, Kowalski K, Pilch W, Antosiewicz J. Fasting and Exercise Induce Changes in Serum Vitamin D Metabolites in Healthy Men. Nutrients 2021; 13:nu13061963. [PMID: 34201027 PMCID: PMC8226906 DOI: 10.3390/nu13061963] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/29/2021] [Accepted: 06/04/2021] [Indexed: 01/19/2023] Open
Abstract
Background: Vitamin D plays pleiotropic roles in the body and hence, changes in its metabolism and distribution during starvation could play an important role in the adaptive response to famine. We aimed to identify the responses of some vitamin D metabolites to 8 d of fasting and exercise. Methods: A repeated-measures design was implemented, in which 14 male volunteers fasted for 8 d and performed an exercise test before and after fasting. Serum samples were collected on day 1 after night fasting and after 8 d of complete food restriction, before and 1 h and 3 h after exercise. Results: After 8 d of fasting, compared with baseline values, serum 24,25(OH)2D3 and 3-epi-25(OH)D3 levels significantly increased; those of 25(OH)D3 and 1,25(OH)2D3 were unaffected; and those of 25(OH)D2 decreased. Exercise on the first day of fasting induced an increase in serum 3-epi-25(OH)D3 levels, while exercise performed after 8 d of fasting induced an increase in 25(OH)D3, 24,25(OH)2D3, 25(OH)D2, and 3-epi-25(OH)D3 levels. Conclusion: Increases in 24,25(OH)2D3 and 3-epi-25(OH)D3 levels imply that fasting stimulates vitamin D metabolism. The effects of exercise on serum vitamin D metabolites, which are most pronounced after fasting and in subjects with serum 25(OH)D3 above 25 ng/mL, support the notion that fasting and exercise augment vitamin D metabolism.
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Affiliation(s)
- Małgorzata Żychowska
- Department of Sport, Faculty of Physical Education, Kazimierz Wielki University, 85-091 Bydgoszcz, Poland;
| | - Rafał Rola
- Masdiag Sp. z o.o. Company, 01-882 Warsaw, Poland; (R.R.); (K.K.)
- Faculty of Chemistry, Nicolaus Copernicus University, 87-100 Torun, Poland
| | - Andżelika Borkowska
- Department of Bioenergetics and Physiology of Exercise, Medical University of Gdansk, 80-210 Gdansk, Poland;
| | - Maja Tomczyk
- Department of Bioenergetics and Nutrition, Faculty of Physical Education, Gdansk University of Physical Education and Sport, 80-336 Gdansk, Poland;
| | - Jakub Kortas
- Department of Health and Life Sciences, Gdansk University of Physical Education and Sport, 80-336 Gdansk, Poland;
| | - Katarzyna Anczykowska
- Department of Biochemistry, Faculty of Physical Education, Gdansk University of Physical Education and Sport, 80-336 Gdansk, Poland;
| | - Karol Pilis
- Department of Health Sciences, Jan Dlugosz University, 42-200 Czestochowa, Poland;
| | - Konrad Kowalski
- Masdiag Sp. z o.o. Company, 01-882 Warsaw, Poland; (R.R.); (K.K.)
| | - Wanda Pilch
- Institute for Basics Sciences, Faculty of Physiotherapy, University of Physical Education in Krakow, 31-571 Krakow, Poland;
| | - Jędrzej Antosiewicz
- Department of Bioenergetics and Physiology of Exercise, Medical University of Gdansk, 80-210 Gdansk, Poland;
- Correspondence: ; Tel.: +48-58-3491456
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Yoon JH, Kwon KS. Receptor-Mediated Muscle Homeostasis as a Target for Sarcopenia Therapeutics. Endocrinol Metab (Seoul) 2021; 36:478-490. [PMID: 34218646 PMCID: PMC8258343 DOI: 10.3803/enm.2021.1081] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 05/13/2021] [Accepted: 05/15/2021] [Indexed: 12/19/2022] Open
Abstract
Sarcopenia is a disease characterized by age-related decline of skeletal muscle mass and function. The molecular mechanisms of the pathophysiology of sarcopenia form a complex network due to the involvement of multiple interconnected signaling pathways. Therefore, signaling receptors are major targets in pharmacological strategies in general. To provide a rationale for pharmacological interventions for sarcopenia, we herein describe several druggable signaling receptors based on their role in skeletal muscle homeostasis and changes in their activity with aging. A brief overview is presented of the efficacy of corresponding drug candidates under clinical trials. Strategies targeting the androgen receptor, vitamin D receptor, Insulin-like growth factor-1 receptor, and ghrelin receptor primarily focus on promoting anabolic action using natural ligands or mimetics. Strategies involving activin receptors and angiotensin receptors focus on inhibiting catabolic action. This review may help to select specific targets or combinations of targets in the future.
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Affiliation(s)
- Jong Hyeon Yoon
- Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea
- Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon, Korea
| | - Ki-Sun Kwon
- Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea
- Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon, Korea
- Aventi Inc., Daejeon, Korea
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Pierce JL, Perrien DS. Do Interactions of Vitamin D 3 and BMP Signaling Hold Implications in the Pathogenesis of Fibrodysplasia Ossificans Progressiva? Curr Osteoporos Rep 2021; 19:358-367. [PMID: 33851285 PMCID: PMC8515998 DOI: 10.1007/s11914-021-00673-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/16/2021] [Indexed: 11/24/2022]
Abstract
PURPOSE OF REVIEW Fibrodysplasia ossificans progressiva (FOP) is a debilitating rare disease known for episodic endochondral heterotopic ossification (HO) caused by gain-of-function mutations in ACVR1/ALK2. However, disease severity varies among patients with identical mutations suggesting disease-modifying factors, including diet, may have therapeutic implications. The roles of vitamin D3 in calcium metabolism and chondrogenesis are known, but its effects on BMP signaling and chondrogenesis are less studied. This review attempts to assess the possibility of vitamin D's effects in FOP by exploring relevant intersections of VD3 with mechanisms of FOP flares. RECENT FINDINGS In vitro and in vivo studies suggest vitamin D suppresses inflammation, while clinical studies suggest that vitamin D3 protects against arteriosclerosis and inversely correlates with non-genetic intramuscular HO. However, the enhancement of chondrogenesis, BMP signaling, and possibly Activin A expression by vitamin D may be more relevant in FOP. There appears to be little potential for vitamin D to reduce HO in FOP, but testing the potential for excess vitamin D to promote HO may be warranted.
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Affiliation(s)
- Jessica L Pierce
- Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, 101 Woodruff Circle, WMRB 1027, Atlanta, GA, 30232, USA
| | - Daniel S Perrien
- Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, 101 Woodruff Circle, WMRB 1027, Atlanta, GA, 30232, USA.
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Ricart B, Monteagudo P, Blasco-Lafarga C. Hypovitaminosis D in Young Basketball Players: Association with Jumping and Hopping Performance Considering Gender. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18105446. [PMID: 34069673 PMCID: PMC8160822 DOI: 10.3390/ijerph18105446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 05/12/2021] [Accepted: 05/15/2021] [Indexed: 11/23/2022]
Abstract
This study aimed to verify whether a group of young well-trained basketball players presented deficiencies in vitamin D concentration, and to analyze whether there was an association between vitamin D concentration and jumping and hopping performance. Gender differences were considered. Twenty-seven players from an international high-level basketball club (14 female, 16.00 ± 0.55 years; 13 male, 15.54 ± 0.52 years) participated in this cross-sectional study. Rate of force development was evaluated by means of the Abalakov test (bilateral: AbB; right leg: AbR; left leg: AbL); and the triple hop test (right leg: THR; left leg: THL). Blood samples were collected for the determination of serum 25-hydroxyvitamin D and nutritional status. Vitamin D insufficiency was found in both women (29.14 ± 6.08 ng/mL) and men (28.92 ± 6.40 ng/mL), with no gender differences regarding nutritional scores. Jumping and hopping performance was confirmed to be significantly larger in males (AbL, THR, and THL p < 0.005), whose CV% were always smaller. A positive correlation was found between AbB and vitamin D (r = 0.703) in males, whereas this correlation was negative (−0.611) for females, who also presented a negative correlation (r = −0.666) between THR and vitamin D. A prevalence of hypovitaminosis D was confirmed in young elite athletes training indoors. Nutritional (i.e., calciferol) controls should be conducted throughout the season. Furthermore, whilst performance seems to be affected by low levels of this vitamin in men, these deficiencies appear to have a different association with jumping and hopping in women, pointing to different performance mechanisms. Further studies accounting for differences in training and other factors might delve into these gender differences.
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Affiliation(s)
- Borja Ricart
- Sport Performance and Physical Fitness Research Group (UIRFIDE), Physical Education and Sports Department, University of Valencia, 46010 Valencia, Spain;
- Alqueria LAB, Valencia Basket, 46013 Valencia, Spain
- Correspondence: (B.R.); (P.M.)
| | - Pablo Monteagudo
- Sport Performance and Physical Fitness Research Group (UIRFIDE), Physical Education and Sports Department, University of Valencia, 46010 Valencia, Spain;
- Education and Specific Didactics Department, Jaume I University, 12071 Castellón, Spain
- Correspondence: (B.R.); (P.M.)
| | - Cristina Blasco-Lafarga
- Sport Performance and Physical Fitness Research Group (UIRFIDE), Physical Education and Sports Department, University of Valencia, 46010 Valencia, Spain;
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Do Autism Spectrum and Autoimmune Disorders Share Predisposition Gene Signature Due to mTOR Signaling Pathway Controlling Expression? Int J Mol Sci 2021; 22:ijms22105248. [PMID: 34065644 PMCID: PMC8156237 DOI: 10.3390/ijms22105248] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 05/08/2021] [Accepted: 05/14/2021] [Indexed: 12/22/2022] Open
Abstract
Autism spectrum disorder (ASD) is characterized by uncommon genetic heterogeneity and a high heritability concurrently. Most autoimmune disorders (AID), similarly to ASD, are characterized by impressive genetic heterogeneity and heritability. We conducted gene-set analyses and revealed that 584 out of 992 genes (59%) included in a new release of the SFARI Gene database and 439 out of 871 AID-associated genes (50%) could be attributed to one of four groups: 1. FMRP (fragile X mental retardation protein) target genes, 2. mTOR signaling network genes, 3. mTOR-modulated genes, and 4. vitamin D3-sensitive genes. With the exception of FMRP targets, which are obviously associated with the direct involvement of local translation disturbance in the pathological mechanisms of ASD, the remaining categories are represented among AID genes in a very similar percentage as among ASD predisposition genes. Thus, mTOR signaling pathway genes make up 4% of ASD and 3% of AID genes, mTOR-modulated genes-31% of both ASD and AID genes, and vitamin D-sensitive genes-20% of ASD and 23% of AID genes. The network analysis revealed 3124 interactions between 528 out of 729 AID genes for the 0.7 cutoff, so the great majority (up to 67%) of AID genes are related to the mTOR signaling pathway directly or indirectly. Our present research and available published data allow us to hypothesize that both a certain part of ASD and AID comprise a connected set of disorders sharing a common aberrant pathway (mTOR signaling) rather than a vast set of different disorders. Furthermore, an immune subtype of the autism spectrum might be a specific type of autoimmune disorder with an early manifestation of a unique set of predominantly behavioral symptoms.
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