|
1
|
Fleet JC. Differences in the absorption and metabolism of vitamin D 2, vitamin D 3, and 25 hydroxyvitamin D. J Steroid Biochem Mol Biol 2025; 249:106718. [PMID: 40043817 DOI: 10.1016/j.jsbmb.2025.106718] [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: 12/22/2024] [Revised: 02/15/2025] [Accepted: 03/01/2025] [Indexed: 03/16/2025]
Abstract
A challenge for public health is to make recommendations for the intake of vitamin D to optimize health and prevent disease. Vitamin D supplementation can be accomplished using vitamin D2 (from fungi), vitamin D3 (from vertebrate sources), or as the prehormone 25 hydroxyvitamin D3 (25OHD3). While these three sources are generally effective for raising and maintaining vitamin D status, their effect is not identical. This review will summarize the differences between these molecules in their routes of absorption, their metabolism, degradation, and molecular function.
Collapse
Affiliation(s)
- James C Fleet
- Department of Nutritional Sciences, University of Texas, Austin, TX 78723, United States.
| |
Collapse
|
|
2
|
Vidal M, Lane NE. Vitamin D and Its Role in Rheumatic Diseases. Metabolites 2025; 15:259. [PMID: 40278388 DOI: 10.3390/metabo15040259] [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: 03/09/2025] [Revised: 03/31/2025] [Accepted: 04/04/2025] [Indexed: 04/26/2025] Open
Abstract
Vitamin D is a fat-soluble molecule with pleiotropic effects, acting as a steroid hormone on three main organs: the intestine, bone, and kidney. Among its best-known functions at the skeletal level are regulating bone metabolism and mineralization. In 1983, the presence of vitamin D receptors on the surface of immune cells was described, which led to the discovery of new functions on immunological and inflammatory processes. Currently, we know that vitamin D modulates the adaptative immune system by suppressing cells that produce inflammatory cytokines by downregulation, acting as an important regulator of immunity and the inflammatory response. In this article, we will review the synthesis, metabolic pathways, and the role of vitamin D in rheumatic autoimmune diseases.
Collapse
Affiliation(s)
- Maritza Vidal
- Centro de Diagnóstico de Osteoporosis y Enfermedades Reumáticas (CEDOR), Lima 15036, Peru
| | - Nancy E Lane
- Center for Musculoskeletal Health, University of California at Davis School of Medicine, Sacramento, CA 95817, USA
| |
Collapse
|
|
3
|
Goodin DS. The epidemiology, pathology and pathogenesis of MS: Therapeutic implications. Neurotherapeutics 2025:e00539. [PMID: 40021419 DOI: 10.1016/j.neurot.2025.e00539] [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: 11/02/2024] [Revised: 12/30/2024] [Accepted: 01/22/2025] [Indexed: 03/03/2025] Open
Abstract
Multiple sclerosis (MS) is a chronic, and potentially disabling, inflammatory disease of the central nervous system (CNS). MS is generally characterized by recurrent, and self-limited, episodes of neurological dysfunction, which occur unpredictably and often result in multifocal tissue injury within the CNS. Currently, women are affected two to three times as often as men although this may not have been the case during earlier Time-Periods. The pathogenesis of MS is known to involve both critical genetic and environmental mechanisms. Nevertheless, in addition to these two mechanisms, disease-pathogenesis also involves a "truly" random event. Indeed, it is this random mechanism, which is responsible for the currently-observed (and increasing) excess of women among patients with MS. This review summarizes the current state of knowledge regarding the pathogenesis of MS (includong its epidemiology, pathology, and genetics) and considers the therapeutic implications that these pathogenetic mechanisms have both for our currently available therapies as well as for the possible therapeutic approaches to the management of this potentially disabling condition in the future.
Collapse
Affiliation(s)
- Douglas S Goodin
- University of California, San Francisco and the San Francisco VA Medical Center, 675 Nelson Rising Lane, Suite #221D, San Francisco, CA 94158, USA.
| |
Collapse
|
|
4
|
Hryciuk M, Heleniak Z, Małgorzewicz S, Kowalski K, Antosiewicz J, Koelmer A, Żmijewski M, Dębska-Ślizień A. Assessment of Vitamin D Metabolism Disorders in Hemodialysis Patients. Nutrients 2025; 17:774. [PMID: 40077644 PMCID: PMC11901569 DOI: 10.3390/nu17050774] [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: 01/31/2025] [Revised: 02/13/2025] [Accepted: 02/20/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Patients with end-stage chronic diseases, especially those undergoing hemodialysis (HD), often experience mineral bone disease (MBD), leading to hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH). Vitamin D deficiency and metabolism disorders are also common, resulting from impaired conversion of 25(OH)D3 to its active form, 1,25(OH)2D3, and reduced inactivation to 24,25(OH)2D3. This study aimed to assess the levels of 25(OH)D2, 25(OH)D3, 24,25(OH)2D3, 3-epi-25(OH)D3, and the vitamin D metabolism ratio (VMR) in patients with maintenance HD. METHODS A cross-sectional study was conducted on 66 HD patients (22-90 years, average 61.3 ± 16.4), with a control group of 206 adults without chronic kidney disease (CKD), both without cholecalciferol supplementation. RESULTS the HD patients had significantly lower 25(OH)D3 levels (15 ng/mL vs. 22 ng/mL) and higher deficiency rates (69% vs. 39%) compared to the controls. However, both groups showed similarly low levels of optimal vitamin D3. The HD patients had lower 24,25(OH)D3 levels (0.1 vs. 2.1 ng/mL) and a lower VMR (0.9% vs. 9%). 3-epi-25(OH)D3 levels and its ratio to 25(OH)D3 were significantly lower in the HD group. Alphacalcidol supplementation raised 1,25(OH)2D3 levels (30.4 vs. 16.2 pg/mL) without affecting other vitamin D metabolites. The HD patients had higher levels of 25(OH)D2 compared to the controls (0.61 vs. 0.31 ng/mL). CONCLUSIONS Vitamin D3 reserves are lower, and both functional deficiency and impaired catabolism of vitamin D3 are present in HD patients compared to the general population. The VMR index is the most sensitive parameter for vitamin D3 deficiency assessment, highlighting the importance of measuring 24,25(OH)D3. Alphacalcidol supplementation increases 1,25(OH)2D3 levels without affecting other vitamin D metabolites. 25(OH)D2 is the only metabolite that was higher in HD patients than the controls.
Collapse
Affiliation(s)
- Maksymilian Hryciuk
- Department of Nephrology, Medical University of Gdańsk, Dębinki 7 Street, 80-211 Gdańsk, Poland; (M.H.); (S.M.); (A.D.-Ś.)
| | - Zbigniew Heleniak
- Department of Nephrology, Medical University of Gdańsk, Dębinki 7 Street, 80-211 Gdańsk, Poland; (M.H.); (S.M.); (A.D.-Ś.)
| | - Sylwia Małgorzewicz
- Department of Nephrology, Medical University of Gdańsk, Dębinki 7 Street, 80-211 Gdańsk, Poland; (M.H.); (S.M.); (A.D.-Ś.)
- Department of Clinical Nutrition, Medical University of Gdańsk, Dębinki 7 Street, 80-211 Gdańsk, Poland
| | - Konrad Kowalski
- Department of Bioenergetics and Exercise Physiology, Medical University of Gdańsk, Dębinki 1 Street, 80-211 Gdańsk, Poland; (K.K.); (J.A.)
- Masdiag Laboratory, S. Żeromskiego 33 Street, 01-882 Warsaw, Poland
| | - Jędrzej Antosiewicz
- Department of Bioenergetics and Exercise Physiology, Medical University of Gdańsk, Dębinki 1 Street, 80-211 Gdańsk, Poland; (K.K.); (J.A.)
| | - Anna Koelmer
- Centre of Biostatistics and Bioinformatics Analysis, Medical University of Gdańsk, 1a Dębinki, 80-211 Gdańsk, Poland;
| | - Michał Żmijewski
- Department of Histology, Medical University of Gdańsk, Dębinki 1 Street, 80-211 Gdańsk, Poland;
| | - Alicja Dębska-Ślizień
- Department of Nephrology, Medical University of Gdańsk, Dębinki 7 Street, 80-211 Gdańsk, Poland; (M.H.); (S.M.); (A.D.-Ś.)
| |
Collapse
|
|
5
|
Langerude L, McQuiston A, Atkinson C, Mulligan JK. Intranasal Calcitriol Accelerates Improvement of Sinonasal Inflammation and Olfactory Impairment in Mice After Cessation of Chronic Cigarette-Smoke Exposure. Int Forum Allergy Rhinol 2025. [PMID: 39811909 DOI: 10.1002/alr.23504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 12/02/2024] [Indexed: 01/16/2025]
Abstract
RATIONALE Smoking has been shown to be associated with circulating deficiencies in 25(OH)D3 and reduced sinonasal tissue levels of the active form of vitamin D, 1,25(OH)2D3. Given vitamin D's ability to reduce inflammation, we sought to examine if intranasal (IN) delivery of calcitriol [clinical analog of 1,25(OH)2D3] could reduce inflammation and improve disease severity in a murine model of chronic cigarette smoke-induced sinonasal inflammation (CS-SI). METHODS Mice were exposed to CS 5 h/day, 5 days/week for 9 months, and then began IN calcitriol three times per week for 4 weeks. Micro-CT was used to assess disease severity. Sinonasal tissues were collected for RNA-seq analysis. Olfactory function was assessed using a T-maze odorant avoidance sniff behavior test. Nasal lavage fluid (NALF) was used for cytology and cytokines analysis. RESULTS Quantification of disease severity by micro-CT showed IN calcitriol reduced opacification by 18%, as compared to smoke cessation alone, in which only a 5% reduction was noted. H&E analysis of NAFL demonstrated heightened neutrophil infiltration and neutrophil-associated chemokines in CS-SI mice, which was reduced with IN calcitriol treatment. RNA-seq pathway analysis demonstrated that smoking was associated with odorant binding changes and that calcitriol treatment reduced neutrophil migration and inflammation. Lastly, IN calcitriol reversed olfactory loss caused in CS-SI. CONCLUSIONS IN delivery of calcitriol accelerates inflammatory resolution in the nose and olfactory mucosa after prolonged CS exposure. Furthermore, treatment was associated with improved olfactory function in mice CS-SI, as such local delivery of calcitriol may serve as a novel treatment for modulating sinonasal inflammation.
Collapse
Affiliation(s)
- Logan Langerude
- Department of Surgery, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Alex McQuiston
- Department of Surgery, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Carl Atkinson
- Department of Surgery, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Jennifer K Mulligan
- Division of Division of Rhinology & Skull Base Surgery Department of Otolaryngology, University of Florida, Gainesville, Florida, USA
| |
Collapse
|
|
6
|
Yang HE, Lee BW, Choi IJ, Oh JY, An EJ. Age-dependent effect of vitamin D supplementation on musculoskeletal health in chronic spinal cord injury patients: A pilot study. J Spinal Cord Med 2025; 48:93-102. [PMID: 37851022 PMCID: PMC11749134 DOI: 10.1080/10790268.2023.2257850] [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] [Indexed: 10/19/2023] Open
Abstract
OBJECTIVE To determine the effect of vitamin D supplementation on changes in body composition associated with musculoskeletal health status in patients with chronic SCI and vitamin D deficiency as a response to age. DESIGN Prospective drug-intervention study. SETTING Department of rehabilitation medicine, Veterans Health Service Medical Center. PARTICIPANTS Seventeen patients with vitamin D insufficiency/deficiency (<30 ng/mL) and chronic SCI were divided into two groups: groups A <65 years (n = 8) and B ≥65 years of age (n = 9). INTERVENTIONS Both groups received 800 IU/day cholecalciferol for 12 weeks. OUTCOME MEASURES We used blood samples to evaluate metabolites related to vitamin D, testosterone (T), lipid profiles, and sex hormone-binding globulin (SHBG). Bioelectrical impedance analysis (BIA) was used to evaluate body composition. RESULTS Group A had significantly better baseline clinical characteristics for all BIA measurements. SHGB was significantly higher in Group B (P = 0.003) and albumin was significantly higher in Group A (P = 0.000). When comparing pre- to post-treatment, Group A showed a significant improvement in T (P = 0.042), total cholesterol (P = 0.035), and triglyceride (P = 0.025) levels, whereas Group B significantly increased vitamin D (P = 0.038) and protein mass (PM) (P = 0.034) levels. CONCLUSION This study suggested that addressing vitamin D deficiency in patients with SCI had different effects in young and older adults, with both groups showing positive changes in body composition. Particularly, the increase in PM on BIA measurements in elderly patients at high risk of sarcopenia was encouraging.
Collapse
Affiliation(s)
- Hea-Eun Yang
- Department of Rehabilitation Medicine, Veterans Health Service Medical Center, Seoul, South Korea
| | - Byeong Wook Lee
- Department of Rehabilitation Medicine, Veterans Health Service Medical Center, Seoul, South Korea
| | - I. Jun Choi
- Department of Rehabilitation Medicine, Veterans Health Service Medical Center, Seoul, South Korea
| | - Ji Yeon Oh
- Department of Rehabilitation Medicine, Veterans Health Service Medical Center, Seoul, South Korea
| | - Eui Jin An
- Department of Rehabilitation Medicine, Veterans Health Service Medical Center, Seoul, South Korea
| |
Collapse
|
|
7
|
Becker LL, Tokach MD, Woodworth JC, Goodband RD, DeRouchey JM, Devlikamov MR, Rahe MC, Siepker CL, Sitthicharoenchai P, Gebhardt JT. Influence of added 1,25(OH) 2D 3-glycoside on nursery pig growth performance, bone measurements, and cytokine concentrations. Transl Anim Sci 2024; 8:txae165. [PMID: 39687916 PMCID: PMC11648558 DOI: 10.1093/tas/txae165] [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: 08/23/2024] [Accepted: 11/27/2024] [Indexed: 12/18/2024] Open
Abstract
A total of 2,268 crossbred pigs (L337 × 1050, PIC; initially 5.5 ± 0.18 kg) were used in a 42-d growth study to evaluate the effects of 1,25(OH)2D3-glycoside provided from a plant extract on growth performance, bone characteristics, and serum criteria of nursery pigs. Pigs were weaned at approximately 21 d of age and randomly assigned to 1 of the 3 dietary treatments in a randomized complete block design. A total of 84 pens were used with 27 pigs per pen and 28 replications per treatment with pens blocked by BW and date of entry into the facility. Treatment diets were corn-soybean meal-based and consisted of a control diet (1,653 IU/kg of vitamin D3), or the control diet with 1.2 or 2.0 μg of 1,25(OH)2D3-glycoside/kg. Blood samples were collected from 25 gilts/treatment on days 21 and 42 to assess 25(OH)D3, cytokine concentrations, and antibody titers. At the end of the study, 10 pigs per treatment were euthanized and the right fibula, metacarpal, second and 10th ribs were collected to determine bone density, breaking strength, and percentage bone ash. Overall, there was a tendency (linear, P = 0.067) for a reduction in G:F as added 1,25(OH)2D3-glycoside increased, but no significant effects on final BW, ADG, ADFI, or mortality were observed. There were no treatment × bone interactions for bone breaking strength and bone ash. Percentage bone ash increased (linear, P = 0.030) across all bones as 1,25(OH)2D3-glycoside increased. Treatment did not affect bone ash weight and breaking strength. Metacarpals and 10th ribs had the greatest bone ash weight followed by the fibula with the second ribs having the lowest (P < 0.05). Metacarpals had greater breaking strength compared to all other bones, followed by the fibula and 10th rib, with the second rib having the lowest (P < 0.001). There was a bone × treatment interaction for bone density, where increasing 1,25(OH)2D3-glycoside increased bone density for the second rib (P = 0.012), but there was no treatment difference for other bones. There was no difference between treatments for antibody titers, 25(OH)D3 status, or circulating cytokine concentrations except for IL-8 concentrations which decreased (linear, P = 0.037) as 1,25(OH)2D3-glycoside increased. In summary, adding 1.2 or 2.0 μg 1,25(OH)2D3-glycoside/kg provided from a plant extract to a diet already containing 1,653 IU/kg of vitamin D3 had no effect on growth or the evaluated serum parameters; however, increasing 1,25(OH)2D3-glycoside increased percentage bone ash.
Collapse
Affiliation(s)
- Larissa L Becker
- Department of Animal Sciences and Industry, College of Agriculture, Kansas State University, Manhattan, KSUSA 66506-0201
| | - Mike D Tokach
- Department of Animal Sciences and Industry, College of Agriculture, Kansas State University, Manhattan, KSUSA 66506-0201
| | - Jason C Woodworth
- Department of Animal Sciences and Industry, College of Agriculture, Kansas State University, Manhattan, KSUSA 66506-0201
| | - Robert D Goodband
- Department of Animal Sciences and Industry, College of Agriculture, Kansas State University, Manhattan, KSUSA 66506-0201
| | - Joel M DeRouchey
- Department of Animal Sciences and Industry, College of Agriculture, Kansas State University, Manhattan, KSUSA 66506-0201
| | | | - Michael C Rahe
- Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA 27607
- Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA 50011
| | - Christopher L Siepker
- Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA 50011
| | - Panchan Sitthicharoenchai
- Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA 27607
- Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA 50011
| | - Jordan T Gebhardt
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA 66506-0201
| |
Collapse
|
|
8
|
Dallavalasa S, Tulimilli SV, Bettada VG, Karnik M, Uthaiah CA, Anantharaju PG, Nataraj SM, Ramashetty R, Sukocheva OA, Tse E, Salimath PV, Madhunapantula SV. Vitamin D in Cancer Prevention and Treatment: A Review of Epidemiological, Preclinical, and Cellular Studies. Cancers (Basel) 2024; 16:3211. [PMID: 39335182 PMCID: PMC11430526 DOI: 10.3390/cancers16183211] [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: 08/08/2024] [Revised: 09/12/2024] [Accepted: 09/17/2024] [Indexed: 09/30/2024] Open
Abstract
Inhibition of human carcinomas has previously been linked to vitamin D due to its effects on cancer cell proliferation, migration, angiogenesis, and apoptosis induction. The anticancer activity of vitamin D has been confirmed by several studies, which have shown that increased cancer incidence is associated with decreased vitamin D and that dietary supplementation of vitamin D slows down the growth of xenografted tumors in mice. Vitamin D inhibits the growth of cancer cells by the induction of apoptosis as well as by arresting the cells at the G0/G1 (or) G2/M phase of the cell cycle. Aim and Key Scientific Concepts of the Review: The purpose of this article is to thoroughly review the existing information and discuss and debate to conclude whether vitamin D could be used as an agent to prevent/treat cancers. The existing empirical data have demonstrated that vitamin D can also work in the absence of vitamin D receptors (VDRs), indicating the presence of multiple mechanisms of action for this sunshine vitamin. Polymorphism in the VDR is known to play a key role in tumor cell metastasis and drug resistance. Although there is evidence that vitamin D has both therapeutic and cancer-preventive properties, numerous uncertainties and concerns regarding its use in cancer treatment still exist. These include (a) increased calcium levels in individuals receiving therapeutic doses of vitamin D to suppress the growth of cancer cells; (b) hyperglycemia induction in certain vitamin D-treated study participants; (c) a dearth of evidence showing preventive or therapeutic benefits of cancer in clinical trials; (d) very weak support from proof-of-principle studies; and (e) the inability of vitamin D alone to treat advanced cancers. Addressing these concerns, more potent and less toxic vitamin D analogs have been created, and these are presently undergoing clinical trial evaluation. To provide key information regarding the functions of vitamin D and VDRs, this review provided details of significant advancements in the functional analysis of vitamin D and its analogs and VDR polymorphisms associated with cancers.
Collapse
Affiliation(s)
- Siva Dallavalasa
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory (DST-FIST Supported Center and ICMR Collaborating Center of Excellence—ICMR-CCoE), Department of Biochemistry (DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru 570015, Karnataka, India; (S.D.); (S.V.T.); (V.G.B.); (M.K.); (C.A.U.); (P.G.A.); (S.M.N.)
| | - SubbaRao V. Tulimilli
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory (DST-FIST Supported Center and ICMR Collaborating Center of Excellence—ICMR-CCoE), Department of Biochemistry (DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru 570015, Karnataka, India; (S.D.); (S.V.T.); (V.G.B.); (M.K.); (C.A.U.); (P.G.A.); (S.M.N.)
| | - Vidya G. Bettada
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory (DST-FIST Supported Center and ICMR Collaborating Center of Excellence—ICMR-CCoE), Department of Biochemistry (DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru 570015, Karnataka, India; (S.D.); (S.V.T.); (V.G.B.); (M.K.); (C.A.U.); (P.G.A.); (S.M.N.)
| | - Medha Karnik
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory (DST-FIST Supported Center and ICMR Collaborating Center of Excellence—ICMR-CCoE), Department of Biochemistry (DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru 570015, Karnataka, India; (S.D.); (S.V.T.); (V.G.B.); (M.K.); (C.A.U.); (P.G.A.); (S.M.N.)
| | - Chinnappa A. Uthaiah
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory (DST-FIST Supported Center and ICMR Collaborating Center of Excellence—ICMR-CCoE), Department of Biochemistry (DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru 570015, Karnataka, India; (S.D.); (S.V.T.); (V.G.B.); (M.K.); (C.A.U.); (P.G.A.); (S.M.N.)
| | - Preethi G. Anantharaju
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory (DST-FIST Supported Center and ICMR Collaborating Center of Excellence—ICMR-CCoE), Department of Biochemistry (DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru 570015, Karnataka, India; (S.D.); (S.V.T.); (V.G.B.); (M.K.); (C.A.U.); (P.G.A.); (S.M.N.)
| | - Suma M. Nataraj
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory (DST-FIST Supported Center and ICMR Collaborating Center of Excellence—ICMR-CCoE), Department of Biochemistry (DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru 570015, Karnataka, India; (S.D.); (S.V.T.); (V.G.B.); (M.K.); (C.A.U.); (P.G.A.); (S.M.N.)
| | - Rajalakshmi Ramashetty
- Department of Physiology, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru 570015, Karnataka, India;
| | - Olga A. Sukocheva
- Department of Hepatology, Royal Adelaide Hospital, Port Rd., Adelaide, SA 5000, Australia;
| | - Edmund Tse
- Department of Hepatology, Royal Adelaide Hospital, Port Rd., Adelaide, SA 5000, Australia;
| | | | - SubbaRao V. Madhunapantula
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory (DST-FIST Supported Center and ICMR Collaborating Center of Excellence—ICMR-CCoE), Department of Biochemistry (DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru 570015, Karnataka, India; (S.D.); (S.V.T.); (V.G.B.); (M.K.); (C.A.U.); (P.G.A.); (S.M.N.)
- Special Interest Group in Cancer Biology and Cancer Stem Cells (SIG-CBCSC), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru 570015, Karnataka, India
| |
Collapse
|
|
9
|
Tan WLA, Hudson NJ, Porto Neto LR, Reverter A, Afonso J, Fortes MRS. An association weight matrix identified biological pathways associated with bull fertility traits in a multi-breed population. Anim Genet 2024; 55:495-510. [PMID: 38692842 DOI: 10.1111/age.13431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 02/26/2024] [Accepted: 04/01/2024] [Indexed: 05/03/2024]
Abstract
Using seven indicator traits, we investigated the genetic basis of bull fertility and predicted gene interactions from SNP associations. We used percent normal sperm as the key phenotype for the association weight matrix-partial correlation information theory (AWM-PCIT) approach. Beyond a simple list of candidate genes, AWM-PCIT predicts significant gene interactions and associations for the selected traits. These interactions formed a network of 537 genes: 38 genes were transcription cofactors, and 41 genes were transcription factors. The network displayed two distinct clusters, one with 294 genes and another with 243 genes. The network is enriched in fertility-associated pathways: steroid biosynthesis, p53 signalling, and the pentose phosphate pathway. Enrichment analysis also highlighted gene ontology terms associated with 'regulation of neurotransmitter secretion' and 'chromatin formation'. Our network recapitulates some genes previously implicated in another network built with lower-density genotypes. Sequence-level data also highlights additional candidate genes relevant to bull fertility, such as FOXO4, FOXP3, GATA1, CYP27B1, and EBP. A trio of regulatory genes-KDM5C, LRRK2, and PME-was deemed core to the network because of their overarching connections. This trio probably influences bull fertility through their interaction with genes, both known and unknown as to their role in male fertility. Future studies may target the trio and their target genes to enrich our understanding of male fertility further.
Collapse
Affiliation(s)
- Wei Liang Andre Tan
- School of Chemistry and Molecular Bioscience, The University of Queensland, St Lucia, Queensland, Australia
| | - Nicholas James Hudson
- School of Agriculture and Food Sustainability, The University of Queensland, Gatton, Queensland, Australia
| | | | | | - Juliana Afonso
- School of Chemistry and Molecular Bioscience, The University of Queensland, St Lucia, Queensland, Australia
- Empresa Brasileira de Pesquisa Agropecuária, Pecuária Sudeste, São Carlos, São Paulo, Brazil
| | | |
Collapse
|
|
10
|
Becker LL, Gebhardt JT, Tokach MD, Woodworth JC, Goodband RD, DeRouchey JM, Bergstrom JR, Siepker CL. Effects of added 25(OH)D3 with varying standardized total tract digestible phosphorus concentrations on nursery pig performance, bone characteristics, and serum vitamin D status. J Anim Sci 2024; 102:skae254. [PMID: 39193832 PMCID: PMC11439147 DOI: 10.1093/jas/skae254] [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: 06/26/2024] [Accepted: 08/26/2024] [Indexed: 08/29/2024] Open
Abstract
A total of 360 pigs (DNA 600 × 241; initially 5.8 kg) were used in a 45-d growth study to evaluate the effects of adding 25(OH)D3 with 3 levels of standardized total tract digestible (STTD) P on nursery pig growth performance, bone and urine characteristics, and serum vitamin D. Pigs were weaned at 19 d of age and randomly allotted to 1 of 6 dietary treatments with 5 pigs per pen and 12 replications per treatment. Dietary treatments were arranged in a 2 × 3 factorial with main effects of 25(OH)D3 (0 or 50 µg/kg equivalent to 2,000 IU/kg of vitamin D3; Hy-D, dsm-firmenich, Plainsboro, NJ) and STTD P (70%, 100%, or 130% of the NRC [NRC 2012. Nutrient requirements of swine. 11th rev. ed. Natl. Acad. Press, Washington, DC) requirement estimate on a dietary percentage basis]. All diets contained 1,653 IU/kg of vitamin D3. On day 45, 1 pig per pen was euthanized to collect the right fibula, metacarpal, and 2nd and 10th ribs. Overall, increasing STTD P increased (quadratic, P ≤ 0.003) ADG, ADFI, and G:F with minimal improvement above 100% of the NRC STTD P requirement estimate. Added 25(OH)D3 had no effect on growth performance. Increasing STTD P decreased urinary Ca concentration (linear, P < 0.001) and increased urinary P concentration (quadratic, P < 0.001). When pigs were fed added 25(OH)D3, serum 25(OH)D3 increased (quadratic, P = 0.005) as STTD P increased but no differences were observed when 25(OH)D3 was not added and STTD P increased (25(OH)D3 × STTD P interaction, P = 0.032). When pigs were fed 25(OH)D3, serum 1,25(OH)2D3 increased (quadratic, P < 0.001) as STTD P decreased but the increase was not significant when no 25(OH)D3 was fed (STTD P × 25(OH)D3 interaction, P = 0.002). Bone ash percentage and weight increased (quadratic, P ≤ 0.065) in all bones as STTD P increased. Added 25(OH)D3 had no effect on bone density or bone ash weight; however, the reduction in bone ash percentage observed with reducing STTD P level tended to be less when 25(OH)D3 was provided (linear interaction, P = 0.098). Increasing STTD P decreased the likelihood of abnormal histologic bone lesions in the 10th rib. In summary, added 25(OH)D3 had limited effect on growth performance; however, an increase in serum concentrations of 25(OH)D3 and 24,25(OH)2D3 was observed. The addition of 25(OH)D3 to P-deficient diets increased percentage bone ash. Increasing STTD P to 100% of NRC [NRC 2012. Nutrient requirements of swine. 11th rev. ed. Natl. Acad. Press, Washington, DC] requirement estimate increased growth and 130% of NRC maximized bone ash.
Collapse
Affiliation(s)
- Larissa L Becker
- Department of Animal Sciences and Industry, College of Agriculture, Kansas State University, Manhattan, KS 66506-0201, USA
| | - Jordan T Gebhardt
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506-0201, USA
| | - Mike D Tokach
- Department of Animal Sciences and Industry, College of Agriculture, Kansas State University, Manhattan, KS 66506-0201, USA
| | - Jason C Woodworth
- Department of Animal Sciences and Industry, College of Agriculture, Kansas State University, Manhattan, KS 66506-0201, USA
| | - Robert D Goodband
- Department of Animal Sciences and Industry, College of Agriculture, Kansas State University, Manhattan, KS 66506-0201, USA
| | - Joel M DeRouchey
- Department of Animal Sciences and Industry, College of Agriculture, Kansas State University, Manhattan, KS 66506-0201, USA
| | | | - Christopher L Siepker
- Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA
| |
Collapse
|
|
11
|
Avila E, Noriega-Mejía BJ, González-Macías J, Cortes-Hernández U, García-Quiroz J, García-Becerra R, Díaz L. The Preventive Role of the Vitamin D Endocrine System in Cervical Cancer. Int J Mol Sci 2023; 24:8665. [PMID: 37240017 PMCID: PMC10218637 DOI: 10.3390/ijms24108665] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 05/08/2023] [Accepted: 05/10/2023] [Indexed: 05/28/2023] Open
Abstract
Vitamin D along with its active metabolite calcitriol and its metabolic and signaling system, known as the vitamin D endocrine system, have been widely recognized as a pivotal regulator of calcium homeostasis in addition to non-calcemic antitumoral effects in a variety of human cancers, including cervical cancer. Several studies have found an inverse relationship between the incidence of cervical neoplasia and vitamin D levels. This narrative review updates the current evidence supporting the notion that the vitamin D endocrine system has a preventive role on cervical cancer, mainly in the early phases of the disease, acting at the level of suppressing cell proliferation, promoting apoptosis, modulating inflammatory responses, and probably favoring the clearance of human papillomavirus-dependent cervical lesions. Although an optimal vitamin D status helps in the prevention and regression of low-grade squamous intraepithelial lesions of the cervix, it appears that vitamin D alone or combined with chemotherapeutic agents has little effectivity once advanced cervical cancer is established. These observations suggest that an optimal vitamin D status might exert beneficial actions in the early phases of cervical cancer by preventing its onset and progression.
Collapse
Affiliation(s)
- Euclides Avila
- Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga No. 15, Col. Belisario Domínguez Sección XVI, Tlalpan, Ciudad de México 14080, Mexico; (B.J.N.-M.); (J.G.-M.); (U.C.-H.); (J.G.-Q.); (L.D.)
| | - Bryan Javier Noriega-Mejía
- Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga No. 15, Col. Belisario Domínguez Sección XVI, Tlalpan, Ciudad de México 14080, Mexico; (B.J.N.-M.); (J.G.-M.); (U.C.-H.); (J.G.-Q.); (L.D.)
| | - Jocelyn González-Macías
- Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga No. 15, Col. Belisario Domínguez Sección XVI, Tlalpan, Ciudad de México 14080, Mexico; (B.J.N.-M.); (J.G.-M.); (U.C.-H.); (J.G.-Q.); (L.D.)
| | - Ulises Cortes-Hernández
- Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga No. 15, Col. Belisario Domínguez Sección XVI, Tlalpan, Ciudad de México 14080, Mexico; (B.J.N.-M.); (J.G.-M.); (U.C.-H.); (J.G.-Q.); (L.D.)
| | - Janice García-Quiroz
- Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga No. 15, Col. Belisario Domínguez Sección XVI, Tlalpan, Ciudad de México 14080, Mexico; (B.J.N.-M.); (J.G.-M.); (U.C.-H.); (J.G.-Q.); (L.D.)
| | - Rocío García-Becerra
- Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Av. Universidad 3000, Coyoacán, Ciudad de México 04510, Mexico;
| | - Lorenza Díaz
- Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga No. 15, Col. Belisario Domínguez Sección XVI, Tlalpan, Ciudad de México 14080, Mexico; (B.J.N.-M.); (J.G.-M.); (U.C.-H.); (J.G.-Q.); (L.D.)
| |
Collapse
|
|
12
|
Clinical Trial to Assess Physiology and Activity of Masticatory Muscles of Complete Denture Wearer Following Vitamin D Intervention. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59020410. [PMID: 36837611 PMCID: PMC9961876 DOI: 10.3390/medicina59020410] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 02/06/2023] [Accepted: 02/14/2023] [Indexed: 02/22/2023]
Abstract
Background and Objectives: Little information is available on the role of Vitamin D as a micro-nutrient deficiency with masticatory muscle efficiency and its effect on the function of removable prosthesis. The aim of this study was to evaluate the role of vitamin D on masticatory muscle activity among completely edentulous patients and its effect on the retention of removable complete dentures (RCDs). Materials and Methods: A non-randomized clinical control trial was conducted on completely edentulous patients (60.53 ± 7.01 years) in the Indian population between 2017 and 2019. Subjects were evaluated for temporomandibular disorders according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Serum Vitamin D (S Vit D) levels, Ultrasonography (USG), and surface Electromyography (sEMG) readings of the masseter muscle were recorded at enrolment (Level 0), after 3 months of Vitamin D therapy (Level 3), and after consecutive 3 months of maintenance therapy, i.e., after 6 months from baseline (Level 6). The fabrication of new RCDs was done for all after the enrolment, and the retention of RCDs was assessed by asking a question regarding denture retention and asking respondents to mark their satisfaction on a 5-point Likert scale. Data were analysed using ANOVA, Paired'-test and Pearson correlation coefficients. A p-value less than 0.05 indicated a statistically significant association. Results: Between enrolment and a six-month follow-up, S Vit D levels showed an increase from 16.03 ± 5.68 ng/mL to 31.35 ± 9.28 ng/mL, showing an increase of 15.32 ± 9.38 ng/mL (95.57% rise). Statistically significant values were observed for USG and sEMG. Conclusions: Results showed that S Vit D affects masticatory muscle activity by improving its thickness and boosting its tonicity. Healthy muscles assist in the retention of RCDs, consequently aiding in mastication, speech, and phonetics, hence improving patient satisfaction. Clinical implication: Acknowledging the fact that the prevalence of Vitamin D deficiency is worldwide. We suggest Vitamin D therapy as a nutritional intervention among the elderly completely edentulous population, following dietary counselling, and consider Vitamin D therapy to be an adjunct to nutritional counselling for improving masticatory muscle activity and efficiency, which aids in RCD retention and stability. Consequently, improving oral health-related quality of life for individuals.
Collapse
|
|
13
|
Iskander PA, Patel P, Patel R, Shafi C, Zheng J, Iskander A, Miller J. Sarcoid Here, Sarcoid There, Sarcoid Everywhere. Cureus 2023; 15:e34904. [PMID: 36938198 PMCID: PMC10016729 DOI: 10.7759/cureus.34904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/12/2023] [Indexed: 02/17/2023] Open
Abstract
Although usually more associated with the lungs, sarcoidosis can have multiple extrapulmonary manifestations. We present a case of a patient with previous biopsy-proven sarcoidosis who was admitted to the hospital secondary to worsening shortness of breath. The patient was found to be positive for Respiratory Syncytial Virus (RSV) which was believed to have exacerbated his pulmonary symptoms. He was treated with IV steroids, nebulizers, and antibiotics which ultimately helped relieve his symptoms. In terms of his sarcoidosis, he was previously treated in the past with steroids in regards to this pathology (which is the mainstay of treatment); while on the regimen, the patient noted his breathing was improved. Of note, he did also have a history of renal cell carcinoma (RCC) status post nephrectomy which was initially evaluated for possible sarcoidosis involvement. This medical therapy could also have been the reason his sarcoidosis did not progress to involve other organs.
Collapse
Affiliation(s)
- Peter A Iskander
- Internal Medicine, The Wright Center for Graduate Medical Education, Scranton, USA
| | - Preya Patel
- Internal Medicine, The Wright Center for Graduate Medical Education, Scranton, USA
| | - Ronakkumar Patel
- Internal Medicine, The Wright Center for Graduate Medical Education, Scranton, USA
| | - Chilsia Shafi
- Internal Medicine, The Wright Center for Graduate Medical Education, Scranton, USA
| | - Jiayi Zheng
- Internal Medicine, The Wright Center for Graduate Medical Education, Scranton, USA
| | - Anthony Iskander
- Internal Medicine, Xavier University School of Medicine, Oranjestad, ABW
| | - Jacob Miller
- Internal Medicine, Wilkes-Barre VA Medical Center, Scranton, USA
| |
Collapse
|
|
14
|
Frank L, Brandt S, Wabitsch M. Subcutaneous fat necrosis in newborns: a systematic literature review of case reports and model of pathophysiology. Mol Cell Pediatr 2022; 9:18. [PMID: 36427118 PMCID: PMC9700527 DOI: 10.1186/s40348-022-00151-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 11/09/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Subcutaneous fat necrosis of the newborn (SCFN) is a rare disease occurring in the first days of life. Characteristically, the infants show hard nodules in subcutaneous tissue, purple or erythematous in color and appear on the upper back, cheeks, buttocks and limbs. In most cases, SCFN is a self-limiting disease, as the nodules disappear in up to 6 months. A severe complication associated with SCFN is hypercalcaemia. Pathophysiological mechanisms causing SCFN or associated hypercalcaemia are not fully understood yet. METHODS A systematic literature research including the six biggest databases for medical research has been used to identify all published case reports of SCFN. N = 206 publications has been identified containing n = 320 case reports. All cases have been classified into four subgroups (depending on reported serum-calcium-level): hypercalcaemia, normocalcaemia, hypocalcaemia or no information given. Reported maternal factors, birth characteristics, details about SCFN, diagnostics, therapy and long-term observations have been extracted from publications. RESULTS This is the first systematic literature research that summed up all published cases of SCFN from 1948 up to 2018. Information about serum calcium level was given in 64.3% of the cases. From those, the majority showed hypercalcaemia (70.5%) (normocalcaemia 25.1%, hypocalcemia 4.3%). 89.3% of newborns with hypercalcaemia showed suppressed levels of the parathormone. Maternal gestational diabetes, maternal hypertensive diseases during pregnancy, macrosomia (> 4000g), asphyxia and therapeutic hypothermia are risk factors for SCFN. Histological findings showed a granulomatous inflammation in 98% of cases. CONCLUSION We identified that maternal, birth characteristics and therapeutic measures are probably risk factors for SCFN. These risk factors should be taken into account within the care of neonates.
Collapse
Affiliation(s)
- Leonie Frank
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
- Department of Orthopaedics and Trauma Surgery, Oberschwaben Clinic Wangen im Allgäu, Wangen im Allgäu, Germany
| | - Stephanie Brandt
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
| | - Martin Wabitsch
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
| |
Collapse
|
|
15
|
Uthailak N, Adisakwattana P, Thiangtrongjit T, Limpanont Y, Chusongsang P, Chusongsang Y, Tanasarnprasert K, Reamtong O. Discovery of Schistosoma mekongi circulating proteins and antigens in infected mouse sera. PLoS One 2022; 17:e0275992. [PMID: 36227939 PMCID: PMC9562170 DOI: 10.1371/journal.pone.0275992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 09/27/2022] [Indexed: 11/24/2022] Open
Abstract
Schistosomiasis is a neglected tropical disease caused by an infection of the parasitic flatworms schistosomes. Schistosoma mekongi is a restricted Schistosoma species found near the Mekong River, mainly in southern Laos and northern Cambodia. Because there is no vaccine or effective early diagnosis available for S. mekongi, additional biomarkers are required. In this study, serum biomarkers associated with S. mekongi-infected mice were identified at 14-, 28-, 42-, and 56-days post-infection. Circulating proteins and antigens of S. mekongi in mouse sera were analyzed using mass spectrometry-based proteomics. Serine protease inhibitors and macrophage erythroblast attacher were down-regulated in mouse sera at all infection timepoints. In addition, 54 circulating proteins and 55 antigens of S. mekongi were identified. Notable circulating proteins included kyphoscoliosis peptidase and putative tuberin, and antigens were detected at all four infection timepoints, particularly in the early stages (12 days). The putative tuberin sequence of S. mekongi was highly similar to homologs found in other members of the genus Schistosoma and less similar to human and murine sequences. Our study provided the identity of promising diagnostic biomarkers that could be applicable in early schistosomiasis diagnosis and vaccine development.
Collapse
Affiliation(s)
- Naphatsamon Uthailak
- Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Poom Adisakwattana
- Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Tipparat Thiangtrongjit
- Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Yanin Limpanont
- Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Phiraphol Chusongsang
- Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Yupa Chusongsang
- Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Kanthi Tanasarnprasert
- Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Onrapak Reamtong
- Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- * E-mail:
| |
Collapse
|
|
16
|
Ip TST, Fu SC, Ong MTY, Yung PSH. Vitamin D deficiency in athletes: Laboratory, clinical and field integration. Asia Pac J Sports Med Arthrosc Rehabil Technol 2022; 29:22-29. [PMID: 35847194 PMCID: PMC9256943 DOI: 10.1016/j.asmart.2022.06.001] [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: 11/12/2021] [Revised: 05/12/2022] [Accepted: 06/07/2022] [Indexed: 11/28/2022] Open
Abstract
Vitamin D deficiency is highly prevalent in athletes. Increased utilisation and storage depletion may be key contributing factor. We found a higher prevalence of vitamin D inadequacy (deficiency/ insufficiency) in power than endurance sport athletes, which may be related to vitamin D utilisation and reserve in skeletal muscles.
Collapse
Affiliation(s)
- Tina Shuk-Tin Ip
- Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region
| | - Sai-Chuen Fu
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Michael Tim-Yun Ong
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Patrick Shu-Hang Yung
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong Special Administrative Region
| |
Collapse
|
|
17
|
The Impact of Chronic Kidney Disease on Nutritional Status and Its Possible Relation with Oral Diseases. Nutrients 2022; 14:nu14102002. [PMID: 35631140 PMCID: PMC9143067 DOI: 10.3390/nu14102002] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 05/02/2022] [Accepted: 05/07/2022] [Indexed: 02/01/2023] Open
Abstract
Several studies have demonstrated a strong relation between periodontal diseases and chronic kidney disease (CKD). The main mechanisms at the base of this link are malnutrition, vitamin dysregulation, especially of B-group vitamins and of C and D vitamins, oxidative stress, metabolic acidosis and low-grade inflammation. In particular, in hemodialysis (HD) adult patients, an impairment of nutritional status has been observed, induced not only by the HD procedures themselves, but also due to numerous CKD-related comorbidities. The alteration of nutritional assessment induces systemic manifestations that have repercussions on oral health, like oral microbiota dysbiosis, slow healing of wounds related to hypovitaminosis C, and an alteration of the supporting bone structures of the oral cavity related to metabolic acidosis and vitamin D deficiency. Low-grade inflammation has been observed to characterize periodontal diseases locally and, in a systemic manner, CKD contributes to the amplification of the pathological process, bidirectionally. Therefore, CKD and oral disease patients should be managed by a multidisciplinary professional team that can evaluate the possible co-presence of these two pathological conditions, that negatively influence each other, and set up therapeutic strategies to treat them. Once these patients have been identified, they should be included in a follow-up program, characterized by periodic checks in order to manage these pathological conditions.
Collapse
|
|
18
|
Zorzella-Pezavento SFG, Mimura LAN, Denadai MB, de Souza WDF, Fraga-Silva TFDC, Sartori A. Is there a window of opportunity for the therapeutic use of vitamin D in multiple sclerosis? Neural Regen Res 2022; 17:1945-1954. [PMID: 35142671 PMCID: PMC8848597 DOI: 10.4103/1673-5374.335139] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Multiple sclerosis is an autoimmune treatable but not curable disease. There are a multiplicity of medications for multiple sclerosis therapy, including a class entitled disease-modifying drugs that are mainly indicated to reduce the number and severity of disease relapses. Not all patients respond well to these therapies, and minor to severe adverse effects have been reported. Vitamin D, called sunshine vitamin, is being studied as a possible light at the end of the tunnel. In this review, we recapitulated the similar immunopathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis, the immunomodulatory and neuroprotective potential of vitamin D and the state-of-art concerning its supplementation to multiple sclerosis patients. Finally, based on our and other groups’ experimental findings, we analyzed the need to consider the relevance of the route and the different time-point administration aspects for a more rational indication of this vitamin to multiple sclerosis patients.
Collapse
Affiliation(s)
| | - Luiza Ayumi Nishiyama Mimura
- Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Marina Bonifácio Denadai
- Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - William Danilo Fernandes de Souza
- Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | | | - Alexandrina Sartori
- Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| |
Collapse
|
|
19
|
Andrukhov O, Blufstein A, Behm C. A Review of Antimicrobial Activity of Dental Mesenchymal Stromal Cells: Is There Any Potential? FRONTIERS IN ORAL HEALTH 2022; 2:832976. [PMID: 35098213 PMCID: PMC8795861 DOI: 10.3389/froh.2021.832976] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 12/21/2021] [Indexed: 12/19/2022] Open
Abstract
Antimicrobial defense is an essential component of host-microbial homeostasis and contributes substantially to oral health maintenance. Dental mesenchymal stromal cells (MSCs) possess multilineage differentiation potential, immunomodulatory properties and play an important role in various processes like regeneration and disease progression. Recent studies show that dental MSCs might also be involved in antibacterial defense. This occurs by producing antimicrobial peptides or attracting professional phagocytic immune cells and modulating their activity. The production of antimicrobial peptides and immunomodulatory abilities of dental MSCs are enhanced by an inflammatory environment and influenced by vitamin D3. Antimicrobial peptides also have anti-inflammatory effects in dental MSCs and improve their differentiation potential. Augmentation of antibacterial efficiency of dental MSCs could broaden their clinical application in dentistry.
Collapse
Affiliation(s)
- Oleh Andrukhov
- Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
| | - Alice Blufstein
- Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
- Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
| | - Christian Behm
- Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
|
20
|
Shenoy S. Gut microbiome, Vitamin D, ACE2 interactions are critical factors in immune-senescence and inflammaging: key for vaccine response and severity of COVID-19 infection. Inflamm Res 2022; 71:13-26. [PMID: 34738147 PMCID: PMC8568567 DOI: 10.1007/s00011-021-01510-w] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 09/21/2021] [Accepted: 09/23/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The SARS-CoV-2 pandemic continues to spread sporadically in the Unites States and worldwide. The severity and mortality excessively affected the frail elderly with co-existing medical diseases. There is growing evidence that cross-talk between the gut microbiome, Vitamin D and RAS/ACE2 system is essential for a balanced functioning of the elderly immune system and in regulating inflammation. In this review, we hypothesize that the state of gut microbiome, prior to infection determines the outcome associated with COVID-19 sepsis and may also be a critical factor in success to vaccination. METHODS Articles from PubMed/Medline searches were reviewed using a combination of terms "SARS-CoV-2, COVID-19, Inflammaging, Immune-senescence, Gut microbiome, Vitamin D, RAS/ACE2, Vaccination". CONCLUSION Evidence indicates a complex association between gut microbiota, ACE-2 expression and Vitamin D in COVID-19 severity. Status of gut microbiome is highly predictive of the blood molecular signatures and inflammatory markers and host responses to infection. Vitamin D has immunomodulatory function in innate and adaptive immune responses to viral infection. Anti-inflammatory functions of Vit D include regulation of gut microbiome and maintaining microbial diversity. It promotes growth of gut-friendly commensal strains of Bifida and Fermicutus species. In addition, Vitamin D is a negative regulator for expression of renin and interacts with the RAS/ ACE/ACE-2 signaling axis. Collectively, this triad may be the critical, link in determination of outcomes in SARS-CoV-2 infection. The presented data are empirical and informative. Further research using advanced systems biology techniques and artificial intelligence-assisted integration could assist with correlation of the gut microbiome with sepsis and vaccine responses. Modulating these factors may impact in guiding the success of vaccines and clinical outcomes in COVID-19 infections.
Collapse
Affiliation(s)
- Santosh Shenoy
- Department of Surgery, Kansas City VA Medical Center, University of Missouri Kansas City, 4801 E Linwood Blvd., Kansas City , MO, 64128, USA.
| |
Collapse
|
|
21
|
Most A, Dörr O, Nef H, Hamm C, Bauer T, Bauer P. Influence of 25-Hydroxy-Vitamin D Insufficiency on Maximal Aerobic Power in Elite Indoor Athletes: A Cross-Sectional Study. SPORTS MEDICINE-OPEN 2021; 7:74. [PMID: 34648100 PMCID: PMC8517059 DOI: 10.1186/s40798-021-00363-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 09/21/2021] [Indexed: 11/21/2022]
Abstract
Background The impact of vitamin D on musculoskeletal health is well-established, although its influence on physical performance is unclear. Therefore, we conducted this study to evaluate the impact of 25-hydroxy-vitamin D (25-OH vitamin D) concentrations with maximal aerobic power of professional indoor athletes.
Results A total of 112 male professional athletes were included in this cross-sectional study, consisting of 88 handball and 24 ice hockey players. The maximal aerobic power was assessed with a standardized cycling ergometer test. Athletes were assigned to two groups according to their 25-OH vitamin D status: insufficient (< 30 ng/mL) and sufficient (≥ 30 ng/mL). Thirty-four players (30.4%) displayed insufficient (21.9 ± 5.9 ng/mL) and 78 (69.6%) sufficient 25-OH vitamin D concentrations (41.6 ± 8.6 ng/mL). Athletes with sufficient levels achieved a higher maximal aerobic power (3.9 ± 0.9 vs. 3.5 ± 0.8 W/kg, p = 0.03) compared to those with insufficient levels. Conclusions There is a high prevalence of 25-OH vitamin D insufficiency in professional indoor athletes, even in summer. Insufficient 25-OH vitamin D concentrations were associated with lower maximal aerobic power in male professional indoor athletes. Further, the 25-OH vitamin D concentration was identified as the only independent predictor of maximal aerobic power in these athletes, highlighting the impact of 25-OH vitamin D on physical performance. Therefore, 25-OH vitamin D concentrations of ≥ 30 ng/mL should be maintained to ensure optimal physical performance in these athletes. Supplementary Information The online version contains supplementary material available at 10.1186/s40798-021-00363-1.
Collapse
Affiliation(s)
- Astrid Most
- Department of Cardiology and Angiology, Justus- Liebig- University Giessen, Klinikstrasse 33, 35392, Giessen, Germany.
| | - Oliver Dörr
- Department of Cardiology and Angiology, Justus- Liebig- University Giessen, Klinikstrasse 33, 35392, Giessen, Germany
| | - Holger Nef
- Department of Cardiology and Angiology, Justus- Liebig- University Giessen, Klinikstrasse 33, 35392, Giessen, Germany
| | - Christian Hamm
- Department of Cardiology and Angiology, Justus- Liebig- University Giessen, Klinikstrasse 33, 35392, Giessen, Germany.,Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany
| | - Timm Bauer
- Department of Cardiology, Internal Intensive Care, General Internal Medicine, Sana Klinikum, Offenbach, Germany
| | - Pascal Bauer
- Department of Cardiology and Angiology, Justus- Liebig- University Giessen, Klinikstrasse 33, 35392, Giessen, Germany
| |
Collapse
|
|
22
|
Chang Villacreses MM, Karnchanasorn R, Panjawatanan P, Ou HY, Chiu KC. Conundrum of vitamin D on glucose and fuel homeostasis. World J Diabetes 2021; 12:1363-1385. [PMID: 34630895 PMCID: PMC8472505 DOI: 10.4239/wjd.v12.i9.1363] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 05/10/2021] [Accepted: 08/05/2021] [Indexed: 02/06/2023] Open
Abstract
As an endocrine hormone, vitamin D plays an important role in bone health and calcium homeostasis. Over the past two decades, the non-calcemic effects of vitamin D were extensively examined. Although the effect of vitamin D on beta cell function were known for some time, the effect of vitamin D on glucose and fuel homeostasis has attracted new interest among researchers. Yet, to date, studies remain inconclusive and controversial, in part, due to a lack of understanding of the threshold effects of vitamin D. In this review, a critical examination of interventional trials of vitamin D in prevention of diabetes is provided. Like use of vitamin D for bone loss, the benefits of vitamin D supplementation in diabetes prevention were observed in vitamin D-deficient subjects with serum 25-hydroxyvitamin D < 50 nmol/L (20 ng/mL). The beneficial effect from vitamin D supplementation was not apparent in subjects with serum 25-hydroxyvitamin D > 75 nmol/L (30 ng/mL). Furthermore, no benefit was noted in subjects that achieved serum 25-hydroxyvitamin D > 100 nmol/L (40 ng/mL). Further studies are required to confirm these observations.
Collapse
Affiliation(s)
- Maria Mercedes Chang Villacreses
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States
| | - Rudruidee Karnchanasorn
- Division of Endocrinology, Department of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States
| | - Panadeekarn Panjawatanan
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY 13326, United States
| | - Horng-Yih Ou
- Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 700, Taiwan
| | - Ken C Chiu
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States
| |
Collapse
|
|
23
|
Chiang MH, Kuo YJ, Chang WC, Wu Y, Lin YC, Jang YC, Chen YP. Association of Vitamin D Deficiency with Low Serum Albumin in Taiwanese Older Adults with Hip Fracture: A Prospective Cross-Sectional Study. J Nutr Sci Vitaminol (Tokyo) 2021; 67:153-162. [PMID: 34193674 DOI: 10.3177/jnsv.67.153] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
The world's population is aging, and the prevalence of hip fracture is rising. Vitamin D deficiency is a risk factor for hip fracture and predicts functional recovery and survival following hip fracture surgery. This cross-sectional study identified the prevalence of vitamin D deficiency in Taiwanese older patients with hip fracture and potential risk factors for vitamin D deficiency. Data from older adults with hip fracture admitted to a single medical center in Taipei, Taiwan were prospectively collected. The preoperative serum 25-hydroxyvitamin D [25(OH)D] concentration and comprehensive clinical history of each patient were examined. A multinomial logistic regression model was used to compare the clinical characteristics of deficient, insufficient, and sufficient 25(OH)D concentration groups. The cohort comprised 310 older adults with hip fracture. The mean age was 80±10 y. The deficient, insufficient, and sufficient groups comprised 180, 84, and 46 patients (58.1%, 27.1%, and 14.8%), respectively. Univariate analysis revealed significant intergroup differences in serum albumin level and body fat percentage and marginally significant differences in serum albumin, estimated glomerular filtration rate, body mass index, and comorbidities of affective or psychotic disorders. In the multinomial logistic regression model, albumin level was the only factor significantly correlated with higher 25(OH)D concentrations in the sufficient and insufficient groups compared with the deficient group. No variable, including preinjury functional status, was significantly correlated with vitamin D deficiency except malnutrition. Our findings may aid the establishment of a robust screening and treatment program for vitamin D deficiency.
Collapse
Affiliation(s)
- Ming-Hsiu Chiang
- Department of General Medicine, Kaohsiung Chang Gung Memorial Hospital
| | - Yi-Jie Kuo
- Department of Orthopedic Surgery, Wan Fang Hospital, Taipei Medical University.,Department of Orthopedic Surgery, School of Medicine, College of Medicine, Taipei Medical University
| | - Wei-Chun Chang
- Department of Orthopedic Surgery, Wan Fang Hospital, Taipei Medical University
| | - Yueh Wu
- Department of Orthopedic Surgery, Wan Fang Hospital, Taipei Medical University
| | - Ying-Chin Lin
- Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University.,Department of Family Medicine, Wan Fang Hospital, Taipei Medical University.,Department of Geriatric Medicine, School of Medicine, College of Medicine, Taipei Medical University
| | - Yeu-Chai Jang
- Department of Obstetrics and Gynecology, Wan Fang Hospital, Taipei Medical University
| | - Yu-Pin Chen
- Department of Orthopedic Surgery, Wan Fang Hospital, Taipei Medical University.,Department of Orthopedic Surgery, School of Medicine, College of Medicine, Taipei Medical University
| |
Collapse
|
|
24
|
Khoshkhui M, Iravani F, Jabbari-Azad F, Zare Marzouni H, Tavakkol-Afshari J, Zamani H, Davarpanah M, Hamidian Jahromi A, Mohammadi M. Significant association between Taq1 gene polymorphism in vitamin D receptor and chronic spontaneous urticaria in the Northeast of Iran. Clin Mol Allergy 2021; 19:6. [PMID: 34044815 PMCID: PMC8161666 DOI: 10.1186/s12948-021-00145-w] [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: 12/22/2020] [Accepted: 04/27/2021] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE Chronic spontaneous urticaria (CSU) is defined as urticaria with an unknown etiology which persists for more than 6 weeks. CSU is an uncomfortable cutaneous condition that occurs due to an immune-mediated inflammatory reaction. Many studies have demonstrated that vitamin D deficiency and single-nucleotide polymorphisms in the vitamin D receptor (VDR) impact the immune response. In the current study, the frequency of the Taq1 polymorphism in the VDR gene were compared between patients with CSU and individuals without CSU. METHODS In a case-control study, a group of CSU patients (n = 100) was compared with a group of healthy age- and gender-matched individuals as a control group (n =100) who visited our center between 2015 and 2017. After DNA extraction from EDTA-containing blood, polymerase chain reaction (PCR-RFLP) was used to determine the presence of the Taq1 polymorphism. Serum vitamin D levels were measured using ELISA method (Abcam, Cambridge, USA). RESULTS Genotyping for Taq1 polymorphism showed that TT, Tt and tt genes frequency in the CSU group were 36%, 54%, and 10% respectively. The TT, Tt and tt genotypes had a distribution of 50%, 47% and 3% respectively in the control group. The mean serum vitamin D level in the CSU group was 19.88 ± 8.14 ng/ml, which was not significantly correlated with the Taq1 polymorphism (P = 0.841). There was a significant relationship between Taq1 gene polymorphism (tt genotype) and CSU (P = 0.038). Tt genotype increased the risk of CSU (odds ratio = 1.596), and inheritance of tt genotype increased the risk even further (odds ratio = 4.630). CONCLUSION The frequency of Taq1 genotype polymorphism in the VDR gene was significantly higher in patients with CSU compared to the control group. The tt genotype polymorphism may be a risk factor for CSU.
Collapse
Affiliation(s)
- Maryam Khoshkhui
- Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Farzaneh Iravani
- Genetic Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Hadi Zare Marzouni
- Qaen School of Nursing and Midwifery, Birjand University of Medical Sciences, Birjand, Iran
| | | | - Hanieh Zamani
- Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Davarpanah
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Mojgan Mohammadi
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| |
Collapse
|
|
25
|
Adelani IB, Rotimi OA, Maduagwu EN, Rotimi SO. Vitamin D: Possible Therapeutic Roles in Hepatocellular Carcinoma. Front Oncol 2021; 11:642653. [PMID: 34113565 PMCID: PMC8185231 DOI: 10.3389/fonc.2021.642653] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 04/06/2021] [Indexed: 12/23/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a unique type of liver cancer instigated by underlying liver diseases. Pre-clinical evidence suggests that HCC progression, like other cancers, could be aided by vitamin D deficiency. Vitamin D is a lipid-soluble hormone usually obtained through sunlight. Vitamin D elucidates its biological responses by binding the vitamin D receptor; thus, promoting skeletal mineralization, and maintain calcium homeostasis. Other reported Vitamin D functions include specific roles in proliferation, angiogenesis, apoptosis, inflammation, and cell differentiation. This review highlighted studies on vitamin D's functional roles in HCC and discussed the specific therapeutic targets from various in vivo, in vitro and clinical studies over the years. Furthermore, it described recent advancements in vitamin D's anticancer effects and its metabolizing enzymes' roles in HCC development. In summary, the review elucidated specific vitamin D-associated target genes that play critical functions in the inhibition of tumorigenesis through inflammation, oxidative stress, invasion, and apoptosis in HCC progression.
Collapse
|
|
26
|
Niculescu DA, Deacu LG, Caragheorgheopol A, Popescu N, Ghemigian A, Procopiuc C, Rosca R, Poiana C. Combined Effects of Vitamin D Status, Renal Function and Age on Serum Parathyroid Hormone Levels. Front Endocrinol (Lausanne) 2021; 12:657991. [PMID: 33995282 PMCID: PMC8120293 DOI: 10.3389/fendo.2021.657991] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 04/14/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Vitamin D status and renal function are well-known independent predictors of serum parathyroid hormone (PTH) levels. We aimed to describe the combined effects of 25-hydroxy vitamin D (25(OH)D), glomerular filtration rate (GFR) and age on serum PTH levels across the whole clinical spectrum. METHODS We retrieved from our endocrinology center database all PTH measurement between 2012 and 2020 for which a simultaneous measurement of serum 25(OH)D, calcium and creatinine was available. Age, sex and diagnosis were available for all subjects. Intact PTH was measured using the same electrochemiluminescence assay. RESULTS There were 6,444 adults and 701 children without a diagnosis of hyper- or hypoparathyroidism or abnormal serum calcium levels. In adults with 25(OH)D≥12 ng/mL multiple regression models showed that serum PTH was negatively correlated with both 25(OH)D and GFR. Regression (-0.68 and -1.59 vs. -0.45 and -0.22 respectively), partial correlation (-0.16 and -0.35 vs. -0.12 and -0.10 respectively) and determination coefficients (0.14 vs. 0.031) were higher in CKD than in normal renal function. In subjects with 25(OH)D<12 ng/mL, GFR was the only significant predictor in those with CKD (β-coefficient=-2.5, r=-0.55) and 25(OH)D was the only significant predictor in those with normal renal function (β-coefficient=-2.05, r=-0.11). Increasing age was associated with higher PTH levels only in those with normal renal function and 25(OH)D≥12 ng/mL. CONCLUSIONS We showed that declining vitamin D and renal function have additive effects on serum PTH in subjects without vitamin D deficiency. In vitamin D deficient subjects this dependency is stronger but is not additive anymore.
Collapse
Affiliation(s)
- Dan Alexandru Niculescu
- Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Pituitary and Neuroendocrine Disorders, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
- *Correspondence: Dan Alexandru Niculescu,
| | - Laura Georgiana Deacu
- Department of Pituitary and Neuroendocrine Disorders, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
| | - Andra Caragheorgheopol
- Research Laboratory, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
| | - Nicoleta Popescu
- Biochemistry Department, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
| | - Adina Ghemigian
- Department of Gonadal Disorders, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
| | - Camelia Procopiuc
- Department of Pediatric Endocrinology, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
| | - Roxana Rosca
- Department of Adrenal and Bone Disorders, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
| | - Catalina Poiana
- Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Pituitary and Neuroendocrine Disorders, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania
| |
Collapse
|
|
27
|
Ruiz-Ballesteros AI, Meza-Meza MR, Vizmanos-Lamotte B, Parra-Rojas I, de la Cruz-Mosso U. Association of Vitamin D Metabolism Gene Polymorphisms with Autoimmunity: Evidence in Population Genetic Studies. Int J Mol Sci 2020; 21:ijms21249626. [PMID: 33348854 PMCID: PMC7766382 DOI: 10.3390/ijms21249626] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 12/08/2020] [Accepted: 12/15/2020] [Indexed: 02/07/2023] Open
Abstract
A high prevalence of vitamin D (calcidiol) serum deficiency has been described in several autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (AR), and systemic lupus erythematosus (SLE). Vitamin D is a potent immunonutrient that through its main metabolite calcitriol, regulates the immunomodulation of macrophages, dendritic cells, T and B lymphocytes, which express the vitamin D receptor (VDR), and they produce and respond to calcitriol. Genetic association studies have shown that up to 65% of vitamin D serum variance may be explained due to genetic background. The 90% of genetic variability takes place in the form of single nucleotide polymorphisms (SNPs), and SNPs in genes related to vitamin D metabolism have been linked to influence the calcidiol serum levels, such as in the vitamin D binding protein (VDBP; rs2282679 GC), 25-hydroxylase (rs10751657 CYP2R1), 1α-hydroxylase (rs10877012, CYP27B1) and the vitamin D receptor (FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) VDR). Therefore, the aim of this comprehensive literature review was to discuss the current findings of functional SNPs in GC, CYP2R1, CYP27B1, and VDR associated to genetic risk, and the most common clinical features of MS, RA, and SLE.
Collapse
Affiliation(s)
- Adolfo I. Ruiz-Ballesteros
- Grupo de Inmunonutrición y Genómica Nutricional en las Enfermedades Autoinmunes, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara Jalisco 44160, Mexico; (A.I.R.-B.); (M.R.M.-M.)
- Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara Jalisco 44340, Mexico
- Programa de Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara Jalisco 44340, Mexico;
| | - Mónica R. Meza-Meza
- Grupo de Inmunonutrición y Genómica Nutricional en las Enfermedades Autoinmunes, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara Jalisco 44160, Mexico; (A.I.R.-B.); (M.R.M.-M.)
- Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara Jalisco 44340, Mexico
- Programa de Doctorado en Ciencias Biomédicas Inmunología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara Jalisco 44340, Mexico
| | - Barbara Vizmanos-Lamotte
- Programa de Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara Jalisco 44340, Mexico;
- Instituto de Nutrigenética y Nutrigenómica Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara Jalisco 44340, Mexico
| | - Isela Parra-Rojas
- Laboratorio de Investigación en Obesidad y Diabetes, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo de los Bravo Guerrero 39087, Mexico;
| | - Ulises de la Cruz-Mosso
- Grupo de Inmunonutrición y Genómica Nutricional en las Enfermedades Autoinmunes, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara Jalisco 44160, Mexico; (A.I.R.-B.); (M.R.M.-M.)
- Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara Jalisco 44340, Mexico
- Programa de Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara Jalisco 44340, Mexico;
- Programa de Doctorado en Ciencias Biomédicas Inmunología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara Jalisco 44340, Mexico
- Correspondence: ; Tel.: +52-1-331-744-15-75
| |
Collapse
|
|
28
|
Zmijewski MA, Carlberg C. Vitamin D receptor(s): In the nucleus but also at membranes? Exp Dermatol 2020; 29:876-884. [PMID: 32654294 DOI: 10.1111/exd.14147] [Citation(s) in RCA: 97] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 06/10/2020] [Accepted: 06/25/2020] [Indexed: 12/11/2022]
Abstract
The genomic actions of the vitamin D are mediated via its biologically most potent metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) and the transcription factor vitamin D receptor (VDR). Activation of VDR by 1,25(OH)2 D3 leads to change in the expression of more 1000 genes in various human tissues. Based on (epi)genome, transcriptome and crystal structure data the molecular details of this nuclear vitamin D signalling pathway are well understood. Vitamin D is known for its role on calcium homeostasis and bone formation, but it also modulates energy metabolism, innate and adaptive immunity as well as cellular growth, differentiation and apoptosis. The observation of rapid, non-genomic effects of 1,25(OH)2 D3 at cellular membranes and in the cytosol initiated the question, whether there are alternative vitamin D-binding proteins in these cellular compartments. So far, the best candidate is the enzyme PDIA3 (protein disulphide isomerase family A member 3), which is found at various subcellular locations. Furthermore, also VDR seems to play a role in membrane-based responses to vitamin D. In this viewpoint, we will dispute whether these rapid, non-genomic pathways are a meaningful addition to the genome-wide effects of vitamin D.
Collapse
Affiliation(s)
| | - Carsten Carlberg
- School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
| |
Collapse
|
|
29
|
Andrukhov O, Blufstein A, Behm C, Moritz A, Rausch-Fan X. Vitamin D3 and Dental Mesenchymal Stromal Cells. APPLIED SCIENCES 2020; 10:4527. [DOI: 10.3390/app10134527] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
Abstract
Vitamin D3 is a hormone involved in the regulation of bone metabolism, mineral homeostasis, and immune response. Almost all dental tissues contain resident mesenchymal stromal cells (MSCs), which are largely similar to bone marrow-derived MSCs. In this narrative review, we summarized the current findings concerning the physiological effects of vitamin D3 on dental MSCs. The existing literature suggests that dental MSCs possess the ability to convert vitamin D3 into 25(OH)D3 and subsequently to the biologically active 1,25(OH)2D3. The vitamin D3 metabolites 25(OH)D3 and 1,25(OH)2D3 stimulate osteogenic differentiation and diminish the inflammatory response of dental MSCs. In addition, 1,25(OH)2D3 influences the immunomodulatory properties of MSCs in different dental tissues. Thus, dental MSCs are both producers and targets of 1,25(OH)2D3 and might regulate the local vitamin D3-dependent processes in an autocrine/paracrine manner. The local vitamin D3 metabolism is assumed to play an essential role in the local physiological processes, but the mechanisms of its regulation in dental MSCs are mostly unknown. The alteration of the local vitamin D3 metabolism may unravel novel therapeutic modalities for the treatment of periodontitis as well as new strategies for dental tissue regeneration.
Collapse
Affiliation(s)
- Oleh Andrukhov
- Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria
| | - Alice Blufstein
- Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria
| | - Christian Behm
- Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria
- Division of Orthodontics, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria
| | - Andreas Moritz
- Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria
| | - Xiaohui Rausch-Fan
- Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria
- Division of Orthodontics, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria
| |
Collapse
|
|
30
|
Meyer MB, Pike JW. Mechanistic homeostasis of vitamin D metabolism in the kidney through reciprocal modulation of Cyp27b1 and Cyp24a1 expression. J Steroid Biochem Mol Biol 2020; 196:105500. [PMID: 31629064 PMCID: PMC6954286 DOI: 10.1016/j.jsbmb.2019.105500] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Revised: 10/07/2019] [Accepted: 10/14/2019] [Indexed: 01/08/2023]
Abstract
Cyp27b1 and Cyp24a1 are reciprocally regulated in the kidney by the key hormones PTH, FGF23, and 1,25(OH)2D3. Our recent genomic studies in mice identified a complex kidney-specific enhancer module located within the introns of adjacent Mettl1 (M1) and Mettl21b (M21) genes that mediate basal and PTH induction of Cyp27b1 as well as suppression by FGF23 and 1,25(OH)2D3. Gross deletion of these segments in mice has severe consequences on skeletal health, and directly affects Cyp27b1 expression in the kidney. Deletion of both M1 and M21 submodules together fully eliminates basal Cyp27b1 expression in the kidney, leading to a systemic and skeletal phenotype similar to that of the Cyp27b1-KO mouse due to depletion of 1,25(OH)2D3 and high PTH. Cyp24a1 levels in the double KO mouse were low due to compensatory regulation by elevated PTH and reduced FGF23. However, expression of Cyp27b1 and retention of its regulation by inflammation (LPS) in the NRTCs remained unperturbed. Dietary normalization of calcium, phosphate, PTH, and FGF23 rescues this aberrant phenotype and normalizes the skeletal issues. Cyp24a1 is controlled by its own unique enhancers for 1,25(OH)2D3, FGF23, and PTH. We were also able to eliminate these activities in mice. Collectively, the hormone-mediated enhancer regulation of both Cyp27b1 and Cyp24a1 in the kidney is responsible for the circulating levels of 1,25(OH)2D3 in the blood which in turn primarily affects calcium and phosphate regulation. Importantly, we can now manipulate this system with our enhancer deletion animal models to study 1,25(OH)2D3 production in non-renal target cells and tissues not only in disease, where it is known to affect the immune system, but also in healthy individuals. Here we will review our studies that have defined a finely balanced homeostatic control mechanism employed by PTH and FGF23 with catastrophic toxicity protection from 1,25(OH)2D3 in the genomic regulation of vitamin D metabolism and its accompanied control of mineral maintenance.
Collapse
Affiliation(s)
- Mark B Meyer
- Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
| | - J Wesley Pike
- Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA
| |
Collapse
|
|
31
|
Harrison SR, Li D, Jeffery LE, Raza K, Hewison M. Vitamin D, Autoimmune Disease and Rheumatoid Arthritis. Calcif Tissue Int 2020; 106:58-75. [PMID: 31286174 PMCID: PMC6960236 DOI: 10.1007/s00223-019-00577-2] [Citation(s) in RCA: 106] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 06/18/2019] [Indexed: 02/06/2023]
Abstract
Vitamin D has been reported to influence physiological systems that extend far beyond its established functions in calcium and bone homeostasis. Prominent amongst these are the potent immunomodulatory effects of the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). The nuclear vitamin D receptor (VDR) for 1,25-(OH)2D3 is expressed by many cells within the immune system and resulting effects include modulation of T cell phenotype to suppress pro-inflammatory Th1 and Th17 CD4+ T cells and promote tolerogenic regulatory T cells. In addition, antigen-presenting cells have been shown to express the enzyme 1α-hydroxylase that converts precursor 25-hydroxyvitamin D3 (25-OHD3) to 1,25-(OH)2D3, so that immune microenvironments are able to both activate and respond to vitamin D. As a consequence of this local, intracrine, system, immune responses may vary according to the availability of 25-OHD3, and vitamin D deficiency has been linked to various autoimmune disorders including rheumatoid arthritis (RA). The aim of this review is to explore the immune activities of vitamin D that impact autoimmune disease, with specific reference to RA. As well as outlining the mechanisms linking vitamin D with autoimmune disease, the review will also describe the different studies that have linked vitamin D status to RA, and the current supplementation studies that have explored the potential benefits of vitamin D for prevention or treatment of RA. The overall aim of the review is to provide a fresh perspective on the potential role of vitamin D in RA pathogenesis and treatment.
Collapse
Affiliation(s)
- Stephanie R Harrison
- Institute of Metabolism and Systems Research, The University of Birmingham, Birmingham, B15 2TT, UK
- Department of Rheumatology, Sandwell and West, Birmingham Hospitals NHS Trust, Birmingham, B18 7QH, UK
| | - Danyang Li
- Institute of Metabolism and Systems Research, The University of Birmingham, Birmingham, B15 2TT, UK
| | - Louisa E Jeffery
- Institute of Translation Medicine, The University of Birmingham, Birmingham, B15 2TT, UK
| | - Karim Raza
- Department of Rheumatology, Sandwell and West, Birmingham Hospitals NHS Trust, Birmingham, B18 7QH, UK
- Institute of Inflammation and Ageing, Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence and MRC Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham, B15 2TT, UK
| | - Martin Hewison
- Institute of Metabolism and Systems Research, The University of Birmingham, Birmingham, B15 2TT, UK.
- Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, B15 2TT, UK.
| |
Collapse
|
|
32
|
Parsanathan R, Jain SK. Glutathione deficiency induces epigenetic alterations of vitamin D metabolism genes in the livers of high-fat diet-fed obese mice. Sci Rep 2019; 9:14784. [PMID: 31616013 PMCID: PMC6794254 DOI: 10.1038/s41598-019-51377-5] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 09/28/2019] [Indexed: 02/06/2023] Open
Abstract
Obesity has been correlating with low levels of glutathione (GSH) and 25-hydroxyvitamin D3 (25(OH)VD3). The liver is the principal site for the 25(OH)VD3 biosynthesis. This study investigated whether GSH deficiency induces epigenetic alterations that impair Vitamin D (VD) metabolism genes in the livers of HFD-fed mice. The expression of the VD metabolism genes CYP2R1 and CYP27A1 (25-hydroxylase), CYP27B1 (1-α-hydroxylase), and vitamin D receptor (VDR) were downregulated in the livers of mice fed an HFD (GSH- deficient) compared with control diet-fed group. The expression of CYP24A1 (24-hydroxylase) was significantly increased, which catabolizes both 25(OH)VD3 and 1α,25-hydroxyvitaminD3. Gene-specific hypermethylation of 25-hydroxylase, 1-α-hydroxylase, and VDR, and hypomethylation of CYP24A1 was observed in HFD-fed mice. GSH deficiency induced in cultured hepatocytes caused an increase in oxidative stress and alterations in VD regulatory genes. Similarly, elevated global DNA methylation, Dnmt activity, and 5-methylcytosine but decreased Tet activity and 5-hydroxymethylcytosine were observed in the GSH-deficient hepatocytes and the liver of HFD-fed mice. Replenishment of GSH by its prodrugs treatment beneficially altered epigenetic enzymes, and VD-metabolism genes in hepatocytes. HFD-induces GSH deficiency and epigenetically alters VD-biosynthesis pathway genes. This provides a biochemical mechanism for the VD-deficiency and potential benefits of GSH treatment in reducing 25(OH)VD3-deficiency.
Collapse
Affiliation(s)
- Rajesh Parsanathan
- Department of Pediatrics and Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center-Shreveport, 1501 Kings Highway, Shreveport, LA, 71130, USA
| | - Sushil K Jain
- Department of Pediatrics and Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center-Shreveport, 1501 Kings Highway, Shreveport, LA, 71130, USA.
| |
Collapse
|
|
33
|
Oliveira Junior LRD, Carvalho TB, Santos RMD, Costa ÉAPND, Pereira PCM, Kurokawa CS. Association of vitamin D3, VDR gene polymorphisms, and LL-37 with a clinical form of Chagas Disease. Rev Soc Bras Med Trop 2019; 52:e20190133. [PMID: 31508781 DOI: 10.1590/0037-8682-0133-2019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 07/24/2019] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION Chagas disease (CD) is an important public health problem in Brazil and worldwide. Aging and obesity are important matters in patients with CD, as is hypovitaminosis D3, which can decrease the quality of life of these patients. Immunomodulation mediated by vitamin D3, especially the production of antimicrobial peptides such as cathelicidin LL-37, might be related to the severity and symptoms of CD. This study aimed to determine the serum levels of vitamin D and LL-37 and VDR gene polymorphisms in patients with chronic CD. METHODS This study included male patients with cardiac and indeterminate clinical forms of CD. Clinical, anthropometric, and blood parameters were obtained. Serum levels of 25(OH)D3 and LL-37 were determined by chemiluminescence and enzyme-linked immunosorbent assay respectively. Fok (rs731236), Bsm (rs1544410), Apa (rs7975232), and Taq (rs731236) polymorphisms of the VDR gene were investigated by PCR-RFLP. RESULTS Sixty-four patients were included in the study: 18 of the cardiac form and 46 of the indeterminate form. No differences in age, ethnicity, BMI, arterial hypertension, diabetes mellitus, or dyslipidemias were observed between groups. However, the serum levels of 25(OH)D3, but not of LL-37, were lower in the cardiac form group. The association among polymorphisms, vitamin D, and clinical form was not significant. CONCLUSIONS Decreased levels of vitamin D suggest an association with the cardiac form of CD. Studies investigating the roles of vitamin D and LL-37 in the immune response and their associations with VDR polymorphisms and disease susceptibility are necessary.
Collapse
Affiliation(s)
| | - Thaysa Buss Carvalho
- Universidade Estadual Paulista, Faculdade de Medicina, Programa de Pós-Graduação em Doenças Tropicais, Botucatu, SP, Brasil
| | - Rodrigo Mattos Dos Santos
- Universidade Estadual Paulista, Faculdade de Medicina, Programa de Pós-Graduação em Doenças Tropicais, Botucatu, SP, Brasil
| | | | - Paulo Câmara Marques Pereira
- Universidade Estadual Paulista, Faculdade de Medicina, Programa de Pós-Graduação em Doenças Tropicais, Botucatu, SP, Brasil
| | - Cilmery Suemi Kurokawa
- Universidade Estadual Paulista, Faculdade de Medicina, Programa de Pós-Graduação em Doenças Tropicais, Botucatu, SP, Brasil
| |
Collapse
|
|
34
|
Hiemstra T, Lim K, Thadhani R, Manson JE. Vitamin D and Atherosclerotic Cardiovascular Disease. J Clin Endocrinol Metab 2019; 104:4033-4050. [PMID: 30946457 PMCID: PMC7112191 DOI: 10.1210/jc.2019-00194] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Accepted: 03/29/2019] [Indexed: 02/07/2023]
Abstract
CONTEXT A large body of experimental and observational data has implicated vitamin D deficiency in the development of cardiovascular disease. However, evidence to support routine vitamin D supplementation to prevent or treat cardiovascular disease is lacking. DESIGN AND RESULTS A comprehensive literature review was performed using PubMed and other literature search engines. Mounting epidemiological evidence and data from Mendelian randomization studies support a link between vitamin D deficiency and adverse cardiovascular health outcomes, but randomized trial evidence to support vitamin D supplementation is sparse. Current public health guidelines restrict vitamin D intake recommendations to the maintenance of bone health and prevention of fractures. Two recently published large trials (VITAL and ViDA) that assessed the role of moderate- to high-dose vitamin D supplementation as primary prevention for cardiovascular outcomes in the general population had null results, and previous randomized trials have also been generally negative. These findings from general population cohorts that are largely replete in vitamin D may not be applicable to chronic kidney disease (CKD) populations, in which the use of active (1α-hydroxylated) vitamin D compounds is prevalent, or to other high-risk populations. Additionally, recent trials in the CKD population, as well as trials using vitamin D analogs, have been limited. CONCLUSIONS Current randomized trials of vitamin D supplementation do not support benefits for cardiovascular health, but the evidence remains inconclusive. Additional randomized trials assessing larger numbers of participants with low baseline vitamin D levels, having longer follow-up periods, and testing higher vitamin D dosages are needed to guide clinical practice.
Collapse
Affiliation(s)
- Thomas Hiemstra
- Cambridge Clinical Trials Unit, Addenbrookes Hospital, Cambridge, UK
- School of Clinical Medicine, University of Cambridge, Cambridge, UK
| | - Kenneth Lim
- Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Ravi Thadhani
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA
| | - JoAnn E. Manson
- Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School and Harvard T.H. Chan School of Public Health, Boston, MA
| |
Collapse
|
|
35
|
Liu TT, Cheong LZ, Man QQ, Zheng X, Zhang J, Song S. Simultaneous profiling of vitamin D metabolites in serum by supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS). J Chromatogr B Analyt Technol Biomed Life Sci 2019; 1120:16-23. [PMID: 31060022 DOI: 10.1016/j.jchromb.2019.04.050] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 04/24/2019] [Accepted: 04/26/2019] [Indexed: 02/06/2023]
Abstract
Simultaneous profiling of serum vitamin D (VD) metabolites with similar structures is a big challenge. Thus, we developed and validated a SFC-MS/MS method, which is capable of eluting hydrophobic molecules, for quantification of VD2/VD3, 25-OH VD2/VD3, 3-epi-25-OH VD2/VD3, 1,25-(OH)2 VD2/VD3 and 24,25-(OH)2 VD2/VD3. VD metabolites were extracted from human serum using acetonitrile solvent. Column stationary phase, elution gradients, flow rate, column temperature, ion-source type and buffer system in post-column make-up solvent were optimized. Baseline separation of 10 VD metabolites can be achieved using PFP column within 10 min; and detection performed under positive electrospray ionization mode allowed quantification of VD metabolites in serum matrix with a limit of quantification (LOQ) varrying from 0.071 to 0.704 ng/mL. The accuracy was controlled with relative bias lower than 5.5% for QC and NIST samples. The developed method showed excellent intra-assay (0.52-7.93% RSD) and inter-assay (1.35-9.04% RSD) precision. The methodology shows enhanced efficiency and sensitivity as compared to LC-MS/MS method using the same column and mass spectrometer, along with significant correlation and low mean difference bias on measurements. For analysis of trace 1,25-(OH)2 VD2 and 1,25-(OH)2 VD3 in normal human serum or plasma, further improvement of LOQ (like derivatization) should be considered. In conclusion, the use of supercritical fluid not only enhanced safety with reduced solvent cost, but also improved retention and sensitivity as compared to LC-MS/MS method. The developed SFC-MS/MS method is appropriate for high throughput analysis of multiple VD metabolites in human serum with reduced solvent and economic cost.
Collapse
Affiliation(s)
- Ting-Ting Liu
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Ling-Zhi Cheong
- Department of Food Science and Technology, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, China
| | - Qing-Qing Man
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Xin Zheng
- Beijing Analysis Center, Shimadzu International Trade (China) Co., Beijing 100020, China
| | - Jian Zhang
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Shuang Song
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
| |
Collapse
|
|
36
|
Grobe M, Kretzschmar G, Vuica A, Filipovic N. Expression of vitamin D receptors in the superior cervical ganglia of rats. Biotech Histochem 2018; 93:320-327. [DOI: 10.1080/10520295.2018.1425910] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- M Grobe
- Department of Anatomy, Histology and Embryology, Laboratory for Neurocardiology, University of Split School of Medicine, Split, Croatia
| | - G Kretzschmar
- Department of Anatomy, Histology and Embryology, Laboratory for Neurocardiology, University of Split School of Medicine, Split, Croatia
| | - A Vuica
- Department of Anatomy, Histology and Embryology, Laboratory for Neurocardiology, University of Split School of Medicine, Split, Croatia
| | - N Filipovic
- Department of Anatomy, Histology and Embryology, Laboratory for Neurocardiology, University of Split School of Medicine, Split, Croatia
| |
Collapse
|
|
37
|
Neelankal John A, Jiang FX. An overview of type 2 diabetes and importance of vitamin D3-vitamin D receptor interaction in pancreatic β-cells. J Diabetes Complications 2018; 32:429-443. [PMID: 29422234 DOI: 10.1016/j.jdiacomp.2017.12.002] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2017] [Revised: 12/03/2017] [Accepted: 12/07/2017] [Indexed: 02/07/2023]
Abstract
One significant health issue that plagues contemporary society is that of Type 2 diabetes (T2D). This disease is characterised by higher-than-average blood glucose levels as a result of a combination of insulin resistance and insufficient insulin secretions from the β-cells of pancreatic islets of Langerhans. Previous developmental research into the pancreas has identified how early precursor genes of pancreatic β-cells, such as Cpal, Ngn3, NeuroD, Ptf1a, and cMyc, play an essential role in the differentiation of these cells. Furthermore, β-cell molecular characterization has also revealed the specific role of β-cell-markers, such as Glut2, MafA, Ins1, Ins2, and Pdx1 in insulin expression. The expression of these genes appears to be suppressed in the T2D β-cells, along with the reappearance of the early endocrine marker genes. Glucose transporters transport glucose into β-cells, thereby controlling insulin release during hyperglycaemia. This stimulates glycolysis through rises in intracellular calcium (a process enhanced by vitamin D) (Norman et al., 1980), activating 2 of 4 proteinases. The rise in calcium activates half of pancreatic β-cell proinsulinases, thus releasing free insulin from granules. The synthesis of ATP from glucose by glycolysis, Krebs cycle and oxidative phosphorylation plays a role in insulin release. Some studies have found that the β-cells contain high levels of the vitamin D receptor; however, the role that this plays in maintaining the maturity of the β-cells remains unknown. Further research is required to develop a more in-depth understanding of the role VDR plays in β-cell function and the processes by which the beta cell function is preserved.
Collapse
Affiliation(s)
- Abraham Neelankal John
- Harry Perkins Institute of Medical Research, Centre for Medical Research, University of Western Australia, Nedlands, Western Australia, Australia; School of Medicine and Pharmacology, University of Western Australia, Carwley, Western Australia, Australia
| | - Fang-Xu Jiang
- Harry Perkins Institute of Medical Research, Centre for Medical Research, University of Western Australia, Nedlands, Western Australia, Australia; School of Medicine and Pharmacology, University of Western Australia, Carwley, Western Australia, Australia.
| |
Collapse
|
|
38
|
Jung YS, Wu D, Smith D, Meydani SN, Han SN. Dysregulated 1,25-dihydroxyvitamin D levels in high-fat diet-induced obesity can be restored by changing to a lower-fat diet in mice. Nutr Res 2018; 53:51-60. [PMID: 29685623 DOI: 10.1016/j.nutres.2018.03.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Revised: 01/04/2018] [Accepted: 03/15/2018] [Indexed: 01/08/2023]
Abstract
Altered regulation of vitamin D metabolites, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D (1,25[OH]2D), was observed in high-fat diet (HFD)-induced obesity. We hypothesized that these HFD-induced changes in vitamin D metabolism would be reversed by decreasing fat mass through dietary intervention. Four-week-old C57BL/6J mice were assigned to 1 of 3 experimental diet groups: (1) the LL group was fed a control diet for 31 weeks, (2) the HH group was fed an HFD for 31 weeks, and (3) the HL group was fed HFD for 15 weeks then switched to the control diet for the remaining 16 weeks. The fat mass of the HL group decreased by 15% from the 14th to the 30th week. Serum 1,25(OH)2D level was significantly higher in the HH group than the LL group, whereas that of the HL group was intermediate to the 2 groups. Serum parathyroid hormone and renal 1-hydroxylase (Cyp27b1) mRNA levels, which are known to stimulate renal 1,25(OH)2D production, were significantly higher in the HH group than the LL group. After losing fat mass, the HL group had significantly lower renal Cyp27b1 mRNA levels than the HH group. No differences were found in serum 25-hydroxyvitamin D levels and mRNA levels of hepatic 25-hydroxylases. In adipose tissue, mRNA levels of 25-hydroxylase and vitamin D receptor were elevated in parallel to the adiposity. In conclusion, serum 1,25(OH)2D levels were closely associated with body adiposity, and reducing fat mass by changing to a lower-fat diet can reverse this obesity-associated increase in circulating 1,25(OH)2D levels.
Collapse
Affiliation(s)
- Young Sun Jung
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Republic of Korea
| | - Dayong Wu
- JM USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA
| | - Donald Smith
- JM USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA
| | - Simin Nikbin Meydani
- JM USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA
| | - Sung Nim Han
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Republic of Korea; Research Institute of Human Ecology, College of Human Ecology, Seoul National University, Seoul, Republic of Korea.
| |
Collapse
|
|
39
|
Aggarwal A, Feldman D, Feldman BJ. Identification of tumor-autonomous and indirect effects of vitamin D action that inhibit breast cancer growth and tumor progression. J Steroid Biochem Mol Biol 2018; 177:155-158. [PMID: 28710021 PMCID: PMC5764828 DOI: 10.1016/j.jsbmb.2017.07.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Revised: 06/29/2017] [Accepted: 07/03/2017] [Indexed: 12/19/2022]
Abstract
Several epidemiological studies have found that low vitamin D levels are associated with worse prognosis and poorer outcomes in patients with breast cancer (BCa), although some studies have failed to find this association. In addition, prior research has found that BCa patients with vitamin D deficiency have a more aggressive molecular phenotype and worse prognostic biomarkers. As vitamin D deficiency is common in patients diagnosed with BCa, elucidating the cause of the association between poor outcomes and vitamin D deficiency promises to have a significant impact on improving care for patients with BCa including enabling the development of novel therapeutic approaches. Here we review our recent findings in this area, including our data revealing that reduction of the expression of the vitamin D receptor (Vdr) within BCa cells accelerates primary tumor growth and enables the development of metastases, demonstrating a tumor autonomous effect of vitamin D signaling to suppress BCa metastases. We believe that these findings are likely relevant to humans as we discovered evidence that a mechanism of VDR regulation identified in our mouse models is conserved in human BCa. In particular, we identified a negative correlation between serum 25(OH)D concentration and the level of expression of the tumor progression factor ID1 in primary tumors from patients with breast cancer.
Collapse
Affiliation(s)
- Abhishek Aggarwal
- Department of Pediatrics, Stanford School of Medicine, Stanford University, CA 94305, United States
| | - David Feldman
- Department of Medicine, Stanford School of Medicine, Stanford University, CA 94305, United States; Stanford Cancer Institute, Stanford University, CA 94305, United States
| | - Brian J Feldman
- Department of Pediatrics, Stanford School of Medicine, Stanford University, CA 94305, United States; Stanford Cancer Institute, Stanford University, CA 94305, United States.
| |
Collapse
|
|
40
|
Dhakal D, Lim SK, Kim DH, Kim BG, Yamaguchi T, Sohng JK. Complete genome sequence of Streptomyces peucetius ATCC 27952, the producer of anticancer anthracyclines and diverse secondary metabolites. J Biotechnol 2018; 267:50-54. [DOI: 10.1016/j.jbiotec.2017.12.024] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Revised: 12/20/2017] [Accepted: 12/30/2017] [Indexed: 01/13/2023]
|
|
41
|
Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25(OH)D3 metabolism. PLoS One 2017; 12:e0186374. [PMID: 29045457 PMCID: PMC5646812 DOI: 10.1371/journal.pone.0186374] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Accepted: 09/30/2017] [Indexed: 12/21/2022] Open
Abstract
RATIONALE Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS). METHODS Balb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined. RESULTS Mice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A. CONCLUSIONS VD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3, even with adequate circulating levels.
Collapse
|
|
42
|
Babar MZM, Hussain M, Majeed SA. Vitamin D supplementation improves FEV1 in patients of Bronchial Asthma. Pak J Med Sci 2017; 33:1144-1147. [PMID: 29142554 PMCID: PMC5673723 DOI: 10.12669/pjms.335.12990] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background and Objective Vitamin D deficiency has strong association with various respiratory disorders in which bronchial asthma is one of them. The objective was to determine the efficacy of vitamin D supplementation in cases with bronchial asthma. Methods This case control study was conducted at private clinical set up of district, Rahim Yar Khan from August to October 2016 in which 100 cases of bronchial asthma were randomly divided into Group-A and Group-B each contained 50 patients. Group-A was given placebo and Group-B with vitamin D in a dose of 50,000 units per day orally. Both the groups were followed in terms of improvement in FEV1 at 1, 2 and 3 months. Results There was no significant difference in both groups in terms of BMI and duration of asthma at start of study. The mean pre treatment vitamin D level of Group-A was 14.23±1.66 and of Group-B, 15.30±2.05 ng/dl (p= 0.23). FEV1 in pre treatment Group-A was 64.35±3.16 and of Group-B was 62.35±2.16 with p= 0.95. There was no significant difference in terms of FEV1 in both the groups at one month (p= 0.32). While at two months it was significantly higher in Group-B with p= 0.04. At 3 months the final outcome was seen where the post treatment FEV1 in Group-A was 66.13±2.75 and in Group-B, 75.15±2.04 with p value of 0.001. Conclusion Vitamin D supplementation improves FEV1 significantly at two months and these can be even highly significant if it is extended up to 3 months.
Collapse
Affiliation(s)
- Muhammad Zafar Majeed Babar
- Muhammad Zafar Majeed Babar, FCPS Medicine. Associate Professor of Medicine, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Pakistan
| | - Mazhar Hussain
- Mazhar Hussain, M. Phil Pharmacology. Assistant Professor of Pharmacology, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Pakistan
| | - Sadia Abdul Majeed
- Sadia Abdul Majeed, MBBS. Demonstrator Anatomy, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Pakistan
| |
Collapse
|
|
43
|
Lee JJ, Plain A, Beggs MR, Dimke H, Alexander RT. Effects of phospho- and calciotropic hormones on electrolyte transport in the proximal tubule. F1000Res 2017; 6:1797. [PMID: 29043081 PMCID: PMC5627579 DOI: 10.12688/f1000research.12097.1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/04/2017] [Indexed: 12/17/2022] Open
Abstract
Calcium and phosphate are critical for a myriad of physiological and cellular processes within the organism. Consequently, plasma levels of calcium and phosphate are tightly regulated. This occurs through the combined effects of the phospho- and calciotropic hormones, parathyroid hormone (PTH), active vitamin D
3, and fibroblast growth factor 23 (FGF23). The organs central to this are the kidneys, intestine, and bone. In the kidney, the proximal tubule reabsorbs the majority of filtered calcium and phosphate, which amounts to more than 60% and 90%, respectively. The basic molecular mechanisms responsible for phosphate reclamation are well described, and emerging work is delineating the molecular identity of the paracellular shunt wherein calcium permeates the proximal tubular epithelium. Significant experimental work has delineated the molecular effects of PTH and FGF23 on these processes as well as their regulation of active vitamin D
3 synthesis in this nephron segment. The integrative effects of both phospho- and calciotropic hormones on proximal tubular solute transport and subsequently whole body calcium-phosphate balance thus have been further complicated. Here, we first review the molecular mechanisms of calcium and phosphate reabsorption from the proximal tubule and how they are influenced by the phospho- and calciotropic hormones acting on this segment and then consider the implications on both renal calcium and phosphate handling as well as whole body mineral balance.
Collapse
Affiliation(s)
- Justin J Lee
- Department of Physiology, University of Alberta, Edmonton, Canada.,The Women and Children's Health Research Institute, Edmonton, Canada
| | - Allein Plain
- Department of Physiology, University of Alberta, Edmonton, Canada.,The Women and Children's Health Research Institute, Edmonton, Canada
| | - Megan R Beggs
- Department of Physiology, University of Alberta, Edmonton, Canada.,The Women and Children's Health Research Institute, Edmonton, Canada
| | - Henrik Dimke
- Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - R Todd Alexander
- Department of Physiology, University of Alberta, Edmonton, Canada.,The Women and Children's Health Research Institute, Edmonton, Canada.,Department of Pediatrics, Edmonton Clinic Health Academy, University of Alberta, Edmonton, Canada
| |
Collapse
|
|
44
|
Fleet JC. The role of vitamin D in the endocrinology controlling calcium homeostasis. Mol Cell Endocrinol 2017; 453:36-45. [PMID: 28400273 PMCID: PMC5529228 DOI: 10.1016/j.mce.2017.04.008] [Citation(s) in RCA: 175] [Impact Index Per Article: 21.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Revised: 04/07/2017] [Accepted: 04/08/2017] [Indexed: 12/14/2022]
Abstract
Vitamin D and its' metabolites are a crucial part of the endocrine system that controls whole body calcium homeostasis. The goal of this hormonal control is to regulate serum calcium levels so that they are maintained within a very narrow range. To achieve this goal, regulatory events occur in coordination at multiple tissues, e.g. the intestine, kidney, bone, and parathyroid gland. Production of the vitamin D endocrine hormone, 1,25 dihydroxyvitamin D (1,25(OH)2 D) is regulated by habitual dietary calcium intake and physiologic states like growth, aging, and the menopause. The molecular actions of 1,25(OH)2 D on calcium regulating target tissues are mediated predominantly by transcription controlled by the vitamin D receptor. A primary role for 1,25(OH)2 D during growth is to increase intestinal calcium absorption so that sufficient calcium is available for bone mineralization. However, vitamin D also has specific actions on kidney and bone.
Collapse
Affiliation(s)
- James C Fleet
- Department of Nutrition Science, Room G1B Stone Hall, Purdue University, West Lafayette, IN 47907-2059, United States.
| |
Collapse
|
|
45
|
Dimitrov V, White JH. Vitamin D signaling in intestinal innate immunity and homeostasis. Mol Cell Endocrinol 2017; 453:68-78. [PMID: 28412519 DOI: 10.1016/j.mce.2017.04.010] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Revised: 04/10/2017] [Accepted: 04/10/2017] [Indexed: 12/14/2022]
Abstract
The lumen of the gut hosts a plethora of microorganisms that participate in food assimilation, inactivation of harmful particles and in vitamin synthesis. On the other hand, enteric flora, a number of food antigens, and toxins are capable of triggering immune responses causing inflammation, which, when unresolved, may lead to chronic conditions such as inflammatory bowel disease (IBD). It is important, therefore, to contain the gut bacteria within the lumen, control microbial load and composition, as well as ensure adequate innate and adaptive immune responses to pathogenic threats. There is growing evidence that vitamin D signaling has impacts on all these aspects of intestinal physiology, contributing to healthy enteric homeostasis. VD was first discovered as the curative agent for nutritional rickets, and its classical actions are associated with calcium absorption and bone health. However, vitamin D exhibits a number of extra-skeletal effects, particularly in innate immunity. Notably, it stimulates production of pattern recognition receptors, anti-microbial peptides, and cytokines, which are at the forefront of innate immune responses. They play a role in sensing the microbiota, in preventing excessive bacterial overgrowth, and complement the actions of vitamin D signaling in enhancing intestinal barrier function. Vitamin D also favours tolerogenic rather than inflammogenic T cell differentiation and function. Compromised innate immune function and overactive adaptive immunity, as well as defective intestinal barrier function, have been associated with IBD. Importantly, observational and intervention studies support a beneficial role of vitamin D supplementation in patients with Crohn's disease, a form of IBD. This review summarizes the effects of vitamin D signaling on barrier integrity and innate and adaptive immunity in the gut, as well as on microbial load and composition. Collectively, studies to date reveal that vitamin D signaling has widespread effects on gut homeostasis, and provide a mechanistic basis for potential therapeutic benefit of vitamin D supplementation in IBD.
Collapse
Affiliation(s)
- Vassil Dimitrov
- Department of Physiology, McGill University, Montreal, Quebec, Canada
| | - John H White
- Department of Physiology, McGill University, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada.
| |
Collapse
|
|
46
|
Wiens J, Ho R, Brassinga AK, Deck CA, Walsh PJ, Ben RN, Mcclymont K, Charlton T, Evans AN, Anderson WG. Biosynthesis of 1α-hydroxycorticosterone in the winter skate Leucoraja ocellata: evidence to suggest a novel steroidogenic route. JOURNAL OF FISH BIOLOGY 2017; 91:260-277. [PMID: 28593636 DOI: 10.1111/jfb.13345] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Revised: 03/30/2017] [Accepted: 05/08/2017] [Indexed: 06/07/2023]
Abstract
The present study explores the ability of intracellular bacteria within the renal-inter-renal tissue of the winter skate Leucoraja ocellata to metabolize steroids and contribute to the synthesis of the novel elasmobranch corticosteroid, 1α-hydroxycorticosterone (1α-OH-B). Despite the rarity of C1 hydroxylation noted in the original identification of 1α-OH-B, literature provides evidence for steroid C1 hydroxylation by micro-organisms. Eight ureolytic bacterial isolates were identified in the renal-inter-renal tissue of L. ocellata, the latter being the site of 1α-OH-B synthesis. From incubations of bacterial isolates with known amounts of potential 1α-OH-B precursors, one isolate UM008 of the genus Rhodococcus was seen to metabolize corticosteroids and produce novel products via HPLC analysis. Cations Zn2+ and Fe3+ altered metabolism of certain steroid precursors, suggesting inhibition of Rhodococcus steroid catabolism. Genome sequencing of UM008 identified strong sequence and structural homology to that of Rhodococcus erythropolis PR4. A complete enzymatic pathway for steroid-ring oxidation as documented within other Actinobacteria was identified within the UM008 genome. This study highlights the potential role of Rhodococcus bacteria in steroid metabolism and proposes a novel alternative pathway for 1α-OH-B synthesis, suggesting a unique form of mutualism between intracellular bacteria and their elasmobranch host.
Collapse
Affiliation(s)
- J Wiens
- Department of Biological Sciences, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada
| | - R Ho
- Department of Microbiology, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada
| | - A K Brassinga
- Department of Microbiology, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada
| | - C A Deck
- Department of Biology, University of Ottawa, Ottawa, Ontario, K1N 6N5, Canada
| | - P J Walsh
- Department of Biology, University of Ottawa, Ottawa, Ontario, K1N 6N5, Canada
| | - R N Ben
- Department of Chemistry, University of Ottawa, Ottawa, ON, K1N 6N5, Canada
| | - K Mcclymont
- Department of Chemistry, University of Ottawa, Ottawa, ON, K1N 6N5, Canada
| | - T Charlton
- Department of Chemistry, University of Ottawa, Ottawa, ON, K1N 6N5, Canada
| | - A N Evans
- Department of Coastal Sciences, Gulf Coast Research Laboratory, University of Southern Mississippi, 703 East Beach Drive, Ocean Springs, MS, U.S.A
| | - W G Anderson
- Department of Biological Sciences, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada
| |
Collapse
|
|
47
|
Creo AL, Thacher TD, Pettifor JM, Strand MA, Fischer PR. Nutritional rickets around the world: an update. Paediatr Int Child Health 2017; 37:84-98. [PMID: 27922335 DOI: 10.1080/20469047.2016.1248170] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Worldwide, nutritional rickets continues to be an evolving problem with several causes. This paper provides an updated literature review characterising the prevalence, aetiology, pathophysiology and treatment of nutritional rickets worldwide. A systematic review of articles on nutritional rickets from various geographical regions was undertaken. For each region, key information was extracted, including prevalence, cause of rickets specific to the region, methods of confirming the diagnosis and current treatment and preventive measures. Calcium deficiency continues to be a major cause of rickets in Africa and Asia. Vitamin D deficiency rickets is perhaps increasing in the Americas, Europe and parts of the Middle East. There continues to be a distinct presentation of calcium-predominant versus vitamin D predominant rickets, although there are overlapping features. More careful diagnosis of rickets and reporting of 25-OHD concentrations has improved accurate knowledge of rickets prevalence and better delineated the cause. Nutritional rickets continues to be an evolving and multi-factorial problem worldwide. It is on a spectrum, ranging from isolated vitamin D deficiency to isolated calcium deficiency. Specific areas which require emphasis include a consistent community approach to screening and diagnosis, vitamin D supplementation of infants and at-risk children, prevention of maternal vitamin D deficiency and the provision of calcium in areas with low calcium diets.
Collapse
Affiliation(s)
- Ana L Creo
- a Department of Pediatric and Adolescent Medicine , Mayo Clinic , Rochester , MN , USA
| | - Tom D Thacher
- b Department of Family Medicine , Mayo Clinic , Rochester , MN , USA
| | - John M Pettifor
- c Wits/SAMRC Developmental Pathways for Health Research Unit, Department of Paediatrics , University of the Witwatersrand , Johannesburg , South Africa
| | - Mark A Strand
- d Pharmacy Practice, Department of Public Health , North Dakota State University , Fargo , ND , USA
| | - Philip R Fischer
- a Department of Pediatric and Adolescent Medicine , Mayo Clinic , Rochester , MN , USA
| |
Collapse
|
|
48
|
Salam SN, Khwaja A, Wilkie ME. Pharmacological Management of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease. Drugs 2017; 76:841-52. [PMID: 27142279 DOI: 10.1007/s40265-016-0575-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD) and is part of the CKD-mineral bone disorder (CKD-MBD). SHPT is associated with increased risk of fracture and mortality; thus, SHPT control is recommended as kidney function declines. Effective SHPT management becomes more difficult once skeletal and cardiovascular adverse effects associated with severe SHPT have become established. However, interventional studies to lower parathyroid hormone (PTH) have so far shown inconsistent results in improving patient-centred outcomes such as mortality, cardiovascular events and fracture. Pharmacological treatment effect on PTH level is also inconsistent between pre-dialysis CKD and dialysis patients, which adds to the complexity of SHPT management. This review aims to give an overview on the pathophysiology, pharmacological and non-pharmacological treatment for SHPT in CKD including some of the limitations of current therapeutic options.
Collapse
Affiliation(s)
- S N Salam
- Sheffield Kidney Institute, Sheffield, UK
| | - A Khwaja
- Sheffield Kidney Institute, Sheffield, UK
| | - M E Wilkie
- Sheffield Kidney Institute, Sheffield, UK.
| |
Collapse
|
|
49
|
Torremadé N, Bozic M, Panizo S, Barrio-Vazquez S, Fernandez-Martín JL, Encinas M, Goltzman D, Arcidiacono MV, Fernandez E, Valdivielso JM. Vascular Calcification Induced by Chronic Kidney Disease Is Mediated by an Increase of 1α-Hydroxylase Expression in Vascular Smooth Muscle Cells. J Bone Miner Res 2016; 31:1865-1876. [PMID: 27074284 DOI: 10.1002/jbmr.2852] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Revised: 04/08/2016] [Accepted: 04/11/2016] [Indexed: 01/08/2023]
Abstract
Vascular calcification (VC) is a complication of chronic kidney disease that predicts morbidity and mortality. Uremic serum promotes VC, but the mechanism involved is unknown. A role for 1,25(OH)2 D3 in VC has been proposed, but the mechanism is unclear because both low and high levels have been shown to increase it. In this work we investigate the role of 1,25(OH)2 D3 produced in vascular smooth muscle cells (VSMCs) in VC. Rats with subtotal nephrectomy and kidney recipient patients showed increased arterial expression of 1α-hydroxylase in vivo. VSMCs exposed in vitro to serum obtained from uremic rats also showed increased 1α-hydroxylase expression. Those increases were parallel to an increase in VC. After 6 days with high phosphate media, VSMCs overexpressing 1α-hydroxylase show significantly higher calcium content and RUNX2 expression than control cells. 1α-hydroxylase null mice (KO) with subtotal nephrectomy and treated with calcitriol (400 ng/kg) for 2 weeks showed significantly lower levels of vascular calcium content, Alizarin red staining, and RUNX2 expression than wild-type (WT) littermates. Serum calcium, phosphorus, blood urea nitrogen (BUN), PTH, and 1,25(OH)2 D3 levels were similar in both calcitriol-treated groups. In vitro, WT VSMCs treated with uremic serum also showed a significant increase in 1α-hydroxylase expression and higher calcification that was not observed in KO cells. We conclude that local activation of 1α-hydroxylase in the artery mediates VC observed in uremia. © 2016 American Society for Bone and Mineral Research.
Collapse
Affiliation(s)
- Noelia Torremadé
- Nephrology Research Department, REDinREN del ISCIII, IRBLleida, University Hospital Arnau de Vilanova, Lleida, Spain
| | - Milica Bozic
- Nephrology Research Department, REDinREN del ISCIII, IRBLleida, University Hospital Arnau de Vilanova, Lleida, Spain
| | - Sara Panizo
- Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, REDinREN del ISCIII, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Sara Barrio-Vazquez
- Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, REDinREN del ISCIII, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Jose L Fernandez-Martín
- Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, REDinREN del ISCIII, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Mario Encinas
- Oncogenic Signaling and Development group. IRBLleida, University of Lleida, Spain
| | - David Goltzman
- Calcium Research Laboratory, McGill University Health Center and Department of Medicine, McGill University, Montréal, Québec, Canada
| | - Maria V Arcidiacono
- Nephrology Research Department, REDinREN del ISCIII, IRBLleida, University Hospital Arnau de Vilanova, Lleida, Spain
| | - Elvira Fernandez
- Nephrology Research Department, REDinREN del ISCIII, IRBLleida, University Hospital Arnau de Vilanova, Lleida, Spain
| | - José M Valdivielso
- Nephrology Research Department, REDinREN del ISCIII, IRBLleida, University Hospital Arnau de Vilanova, Lleida, Spain.
| |
Collapse
|
|
50
|
Agic A, Xu H, Altgassen C, Noack F, Wolfler MM, Diedrich K, Friedrich M, Taylor RN, Hornung D. Relative Expression of 1,25-Dihydroxyvitamin D3 Receptor, Vitamin D 1α-Hydroxylase, Vitamin D 24-Hydroxylase, and Vitamin D 25-Hydroxylase in Endometriosis and Gynecologic Cancers. Reprod Sci 2016; 14:486-97. [PMID: 17913968 DOI: 10.1177/1933719107304565] [Citation(s) in RCA: 104] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The authors demonstrate expression of the vitamin D receptor (VDR) and its hydroxylases in the endometrium and ovaries of women with and without endometriosis and endometrial or ovarian cancer. Immunohistochemistry showed strong staining of the VDR in endometriosis and endometrial cancer, with the most intense staining in epithelial cells. The VDR mRNA was significantly increased in patients with endometrial and ovarian cancer compared to the control group. There was a significantly higher 1 alpha-hydroxylase expression in the endometrium of patients with endometriosis compared to healthy controls. The observed differences in VDR and 1 alpha -hydroxylase mRNA levels were maintained at the protein level. The authors found no differences in 25-OH vitamin D levels between the serum of patients with endometriosis (25.7 +/- 2.1 ng/mL, n = 46) and healthy controls (22.6 +/- 2.0 ng/mL, n = 33, P = .31). They hypothesize that vitamin D might influence the local activity of immune cells and cytokines thought to play important pathogenic roles in the development and maintenance of endometriosis.
Collapse
Affiliation(s)
- Admir Agic
- Department of Gynecology and Obstetrics, University of Schleswig-Holstein, Lübeck, Germany
| | | | | | | | | | | | | | | | | |
Collapse
|