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      Vitamin D: A Potential Star for Treating Chronic Pancreatitis

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          Abstract

          Chronic pancreatitis (CP) is a chronic inflammatory and fibrotic disease of the pancreas. The incidence of CP is increasing worldwide but the effective therapies are lacking. Hence, it is necessary to identify economical and effective agents for the treatment of CP patients. Vitamin D (VD) and its analogues have been confirmed as pleiotropic regulators of cell proliferation, apoptosis, differentiation and autophagy. Clinical studies show that VD deficiency is prevalent in CP patients. However, the correlation between VD level and the risk of CP remains controversial. VD and its analogues have been demonstrated to inhibit pancreatic fibrosis by suppressing the activation of pancreatic stellate cells and the production of extracellular matrix. Limited clinical trials have shown that the supplement of VD can improve VD deficiency in patients with CP, suggesting a potential therapeutic value of VD in CP. However, the mechanisms by which VD and its analogues inhibit pancreatic fibrosis have not been fully elucidated. We are reviewing the current literature concerning the risk factors for developing CP, prevalence of VD deficiency in CP, mechanisms of VD action in PSC-mediated fibrogenesis during the development of CP and potential therapeutic applications of VD and its analogues in the treatment of CP.

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          Most cited references172

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          Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.

          The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.
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            Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

            The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
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              Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy.

              The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment. Conversion of quiescent to activated pancreatic stellate cells (PSCs) drives the severe stromal reaction that characterizes PDA. Here, we reveal that the vitamin D receptor (VDR) is expressed in stroma from human pancreatic tumors and that treatment with the VDR ligand calcipotriol markedly reduced markers of inflammation and fibrosis in pancreatitis and human tumor stroma. We show that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone. This work describes a molecular strategy through which transcriptional reprogramming of tumor stroma enables chemotherapeutic response and suggests vitamin D priming as an adjunct in PDA therapy. PAPERFLICK: Copyright © 2014 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                06 June 2022
                2022
                : 13
                : 902639
                Affiliations
                Department of Hepatic Biliary Pancreatic Medicine , The First Hospital of Jilin University , Changchun, China
                Author notes

                Edited by: Ewa Teresa Marcinkowska, University of Wrocław, Poland

                Reviewed by: Andrzej T. Slominski, University of Alabama at Birmingham, United States

                Utpreksha Vaish, University of Alabama at Birmingham, United States

                *Correspondence: Runping Gao, gaorp@ 123456jlu.edu.cn

                This article was submitted to Gastrointestinal and Hepatic Pharmacology, a section of the journal Frontiers in Pharmacology

                Article
                902639
                10.3389/fphar.2022.902639
                9207250
                35734414
                a6b7323e-fff8-478b-968f-1d63a99d36f9
                Copyright © 2022 Zheng and Gao.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 March 2022
                : 13 May 2022
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                vitamin d,vitamin d receptor,chronic pancreatitis,fibrosis,inflammation

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