Vitamin D pathway regulatory genes encoding 1α-hydroxylase and 24-hydroxylase are dysregulated in sinonasal tissue during chronic rhinosinusitis

2016 ◽  
Vol 7 (2) ◽  
pp. 169-176 ◽  
Author(s):  
Jenna M. Christensen ◽  
Jasmine Cheng ◽  
Peter Earls ◽  
Jenny Gunton ◽  
William Sewell ◽  
...  
Keyword(s):  
Vitamin D ◽  
Chronic Rhinosinusitis ◽  
Regulatory Genes ◽  
Genes Encoding

scholarly journals Relationship of vitamin D3 deficiency and chronic rhinosinusitis with nasal and sinus polyposis in patients referring to the Department of Ear, Nose, and Throat Diseases Department of Vali-asr Hospital in Brigand, Iran

2021 ◽  
pp. 99-104
Keyword(s):  
Vitamin D ◽  
Chronic Rhinosinusitis ◽  
Vitamin D3 ◽  
Sinus Surgery ◽  
Control Group ◽  
Case Group ◽  
Significant Difference ◽  
Relationship Of ◽  
Vitamin D3 Deficiency ◽  
Nose And Throat

Introduction: Chronic rhinosinusitis may require referral to an ear, nose, and throat specialist for possible endoscopic sinus surgery if medical management fails. Vitamin D is one of the essential vitamins for the body that is effective in inflammatory processes. Therefore, it seems necessary to confirm the association between the deficiency of this vitamin and the occurrence of chronic rhinosinusitis with nasal polyposis. This study aimed to determine the relationship of vitamin D3 deficiency and chronic rhinosinusitis with nasal and sinus polyposis in patients referring to the Otorhinolaryngology Department of Valiasr Hospital, Birjand, Iran, in 2017. Methods: A case-control study was performed on individuals, including a group of patients with rhinosinusitis and a control group (n=20 each), referring to the Department of Ear, Nose, and Throat Diseases Department of Vali-asr Hospital. Among patients diagnosed with chronic rhinosinusitis, the cases that had polyps on endoscopic examination were included in the study. After completing the consent form, venous blood samples (10cc) were collected from the patients in fasting conditions. The electrochemical luminescence method was used for measuring the level of serum vitamin D. A questionnaire containing demographic information and clinical findings was completed by reviewing the patients' records. Data analysis was performed in SPSS software (Version. 22)using Chi-square and Mann-Whitney U-tests. Results: The mean and median scores of vitamin D level were obtained at14.13±12.99 and 10.25 in the case group, and 18.72±9.29 and 18.77 in the control group, respectively. The level of vitamin D was significantly higher in the control group than in the chronic group (P=0.04). In the case group, 16 (80%) patients lacked vitamin D and 3 patients had an insufficient level of vitamin D. In the control group, 13 (65%) patients lacked vitamin D and 4 cases had an insufficient level of vitamin D. There was no significant difference in vitamin D levels between the two groups (P=0.61). No significant difference was observed between the two clinical symptoms. Conclusion: It was revealed that the lack of vitamin D was likely to be an effective factor in the rhinosinusitis disease; therefore, proceedings need to be taken to cure the deficiency of this vitamin.

scholarly journals Mitochondrial potassium channels: A novel calcitriol target

2022 ◽  
Vol 27 (1) ◽  
Author(s):  
Anna M. Olszewska ◽  
Adam K. Sieradzan ◽  
Piotr Bednarczyk ◽  
Adam Szewczyk ◽  
Michał A. Żmijewski
Keyword(s):  
Vitamin D ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Mitochondrial Membrane ◽  
Human Keratinocytes ◽  
Inner Mitochondrial Membrane ◽  
Open Probability ◽  
Expression Of Genes ◽  
High Calcium ◽  
Genes Encoding

Abstract Background Calcitriol (an active metabolite of vitamin D) modulates the expression of hundreds of human genes by activation of the vitamin D nuclear receptor (VDR). However, VDR-mediated transcriptional modulation does not fully explain various phenotypic effects of calcitriol. Recently a fast non-genomic response to vitamin D has been described, and it seems that mitochondria are one of the targets of calcitriol. These non-classical calcitriol targets open up a new area of research with potential clinical applications. The goal of our study was to ascertain whether calcitriol can modulate mitochondrial function through regulation of the potassium channels present in the inner mitochondrial membrane. Methods The effects of calcitriol on the potassium ion current were measured using the patch-clamp method modified for the inner mitochondrial membrane. Molecular docking experiments were conducted in the Autodock4 program. Additionally, changes in gene expression were investigated by qPCR, and transcription factor binding sites were analyzed in the CiiiDER program. Results For the first time, our results indicate that calcitriol directly affects the activity of the mitochondrial large-conductance Ca2+-regulated potassium channel (mitoBKCa) from the human astrocytoma (U-87 MG) cell line but not the mitochondrial calcium-independent two-pore domain potassium channel (mitoTASK-3) from human keratinocytes (HaCaT). The open probability of the mitoBKCa channel in high calcium conditions decreased after calcitriol treatment and the opposite effect was observed in low calcium conditions. Moreover, using the AutoDock4 program we predicted the binding poses of calcitriol to the calcium-bound BKCa channel and identified amino acids interacting with the calcitriol molecule. Additionally, we found that calcitriol influences the expression of genes encoding potassium channels. Such a dual, genomic and non-genomic action explains the pleiotropic activity of calcitriol. Conclusions Calcitriol can regulate the mitochondrial large-conductance calcium-regulated potassium channel. Our data open a new chapter in the study of non-genomic responses to vitamin D with potential implications for mitochondrial bioenergetics and cytoprotective mechanisms.

scholarly journals Tripartite combination of potential pandemic mitigation agents: Vitamin D, Quercetin, and Estradiol manifest properties of candidate medicinal agents for mitigation of the severity of pandemic COVID-19 defined by genomics-guided tracing of SARS-CoV-2 targets in human cells.

2020 ◽  
Author(s):  
Gennadi Glinsky
Keyword(s):  
Vitamin D ◽  
Immune Cells ◽  
Randomized Clinical Trials ◽  
Viral Proteins ◽  
Human Cells ◽  
Protein Targets ◽  
Human Genes ◽  
Genes Encoding ◽  
Coronavirus Infection ◽  
Encoding Protein

<p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p>Genes required for SARS-CoV-2 entry into human cells, <i>ACE2</i> and <i>FURIN</i>, were employed as baits to build genomics-guided molecular maps of up-stream regulatory elements, their expression and functions in human body, including pathophysiologically-relevant cell types. Repressors and activators of the <i>ACE2</i> and <i>FURIN</i> genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors (<i>VDR; GATA5; SFTPC; HIF1a</i>) and activators (<i>HMGA2; INSIG1</i>) were then employed to identify existing drugs manifesting gene expression signatures of the potential coronavirus infection mitigation agents. Using this strategy, Vitamin D and Quercetin have been identified as putative COVID-19 mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly similar structurally Quercetin, Luteolin, and Eriodictyol could serve as scaffolds for development of efficient inhibitors of the SARS-CoV-2 infection. In agreement with this notion, Quercetin alters expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both Quercetin and Vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of Testosterone versus Estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during coronavirus pandemic. Estradiol, in contrast with Testosterone, affects expression of a majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of Quercetin/Vitamin D/Estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 coronavirus may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated Vitamin D deficiency may contribute to high mortality of older adults and elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely Vitamin D and Quercetin, as well as of the highly selective (K<sub>i, </sub>600 pm) intrinsically-specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically-viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of Vitamin D and Quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with results of present analyses, a randomized interventional clinical trial entitled “Phase II Clinical Trial of Estradiol to Reduce Severity of COVID19 Infection in COVID19+ and Presumptive COVID19+ Patients” has been posted on ClinicalTrials.gov website (<a href="https://clinicaltrials.gov/ct2/show/NCT04359329">https://clinicaltrials.gov/ct2/show/NCT04359329</a> ) and two interventional randomized clinical trials evaluating effects of Vitamin D on prevention and treatment of COVID-19 were listed on ClinicalTrials.gov website (<a href="https://www.clinicaltrials.gov/ct2/show/NCT04334005">https://www.clinicaltrials.gov/ct2/show/NCT04334005</a> and <a href="https://clinicaltrials.gov/ct2/show/NCT04344041">https://clinicaltrials.gov/ct2/show/NCT04344041</a> ).</p><p> <b></b><i></i><u></u><sub></sub><sup></sup><br></p>

scholarly journals Genetic Variants Shaping Inter-individual Differences in Response to Dietary Intakes—A Narrative Review of the Case of Vitamins

2020 ◽  
Vol 7 ◽  
Author(s):  
Aikaterini Niforou ◽  
Valentini Konstantinidou ◽  
Androniki Naska
Keyword(s):  
Vitamin D ◽  
Vitamin C ◽  
Genetic Variants ◽  
Current Knowledge ◽  
Association Studies ◽  
Genetic Variations ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Dietary Intakes ◽  
Genes Encoding

Recent advances in the field of nutrigenetics have provided evidence on how genetic variations can impact the individuals' response to dietary intakes. An objective and reliable assessment of dietary exposures should rely on combinations of methodologies including frequency questionnaires, short-term recalls or records, together with biological samples to evaluate markers of intake or status and to identify genetic susceptibilities. In an attempt to present current knowledge on how genetic fingerprints contribute to an individual's nutritional status, we present a review of current literature describing associations between genetic variants and levels of well-established biomarkers of vitamin status in free-living and generally healthy individuals. Based on the outcomes of candidate gene, genome-wide-association studies and meta-analyses thereof, we have identified several single nucleotide polymorphisms (SNPs) involved in the vitamins' metabolic pathways. Polymorphisms in genes encoding proteins involved in vitamin metabolism and transport are reported to have an impact on vitamin D status; while genetic variants of vitamin D receptor were most frequently associated with health outcomes. Genetic variations that can influence vitamin E status include SNPs involved in its uptake and transport, such as in SCAR-B1 gene, and in lipoprotein metabolism. Variants of the genes encoding the sodium-dependent vitamin C transport proteins are greatly associated with the body's status on vitamin C. Regarding the vitamins of the B-complex, special reference is made to the widely studied variant in the MTHFR gene. Methodological attributes of genetic studies that may limit the comparability and interpretability of the findings are also discussed. Our understanding of how genes affect our responses to nutritional triggers will enhance our capacity to evaluate dietary exposure and design personalized nutrition programs to sustain health and prevent disease.

scholarly journals Genetic Variation in Genes Encoding Airway Epithelial Potassium Channels Is Associated with Chronic Rhinosinusitis in a Pediatric Population

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e89329 ◽  
Author(s):  
Michael T. Purkey ◽  
Jin Li ◽  
Frank Mentch ◽  
Struan F. A. Grant ◽  
Martin Desrosiers ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Potassium Channels ◽  
Chronic Rhinosinusitis ◽  
Pediatric Population ◽  
Airway Epithelial ◽  
Genes Encoding

scholarly journals Gene Expression Analysis of the Streptococcus pneumoniae Competence Regulons by Use of DNA Microarrays

2000 ◽  
Vol 182 (21) ◽  
pp. 6192-6202 ◽  
Author(s):  
Scott Peterson ◽  
Robin T. Cline ◽  
Hervé Tettelin ◽  
Vasily Sharov ◽  
Donald A. Morrison
Keyword(s):  
Streptococcus Pneumoniae ◽  
Dna Microarrays ◽  
Target Genes ◽  
Expression Patterns ◽  
In Vitro Models ◽  
Regulatory Genes ◽  
Mrna Levels ◽  
Similar Expression Pattern ◽  
Genes Encoding

ABSTRACT Competence for genetic transformation in Streptococcus pneumoniae is coordinated by the competence-stimulating peptide (CSP), which induces a sudden and transient appearance of competence during exponential growth in vitro. Models of this quorum-sensing mechanism have proposed sequential expression of several regulatory genes followed by induction of target genes encoding DNA-processing-pathway proteins. Although many genes required for transformation are known to be expressed only in response to CSP, the relative timing of their expression has not been established. Overlapping expression patterns for the genes cinA andcomD (G. Alloing, B. Martin, C. Granadel, and J. P. Claverys, Mol. Microbiol. 29:75–83, 1998) suggest that at least two distinct regulatory mechanisms may underlie the competence cycle. DNA microarrays were used to estimate mRNA levels for all known competence operons during induction of competence by CSP. The known competence regulatory operons, comAB, comCDE, andcomX, exhibited a low or zero initial (uninduced) signal, strongly increased expression during the period between 5 and 12 min after CSP addition, and a decrease nearly to original values by 15 min after initiation of exposure to CSP. The remaining competence genes displayed a similar expression pattern, but with an additional delay of approximately 5 min. In a mutant defective in ComX, which may act as an alternate sigma factor to allow expression of the target competence genes, the same regulatory genes were induced, but the other competence genes were not. Finally, examination of the expression of 60 candidate sites not previously associated with competence identified eight additional loci that could be induced by CSP.

scholarly journals Review: Immunology of Sinusitis, Trauma, Asthma, and Sepsis

2015 ◽  
Vol 6 (3) ◽  
pp. ar.2015.6.0140 ◽  
Author(s):  
Marianne Frieri ◽  
Krishan Kumar ◽  
Anthony Boutin
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Vitamin D ◽  
Seasonal Variation ◽  
Organ Failure ◽  
Chronic Rhinosinusitis ◽  
Hereditary Angioedema ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Nf Kappa B

Background This review article is important for allergists/immunologists and otolaryngologists. It discussed chronic rhinosinusitis, epidemiology, pathogenesis, innate adaptive immunology, nuclear factor–kappa B related to inflammation, sepsis, complement, reactive oxygen species, asthma, sinusitis, elderly pathogenesis, oxidative stress, depression, seasonal variation, vitamin D, genetic susceptibility and sepsis, hereditary angioedema related to trauma and stress. Objective The objective of this review is to link chronic rhinosinusitis, epidemiology, innate and adaptive immunology, NF-kappa B related to inflammation, sepsis, complement, reactive oxygen species, asthma and sinusitis. Methods A literature search was conducted from several articles, prospective studies, recent reviews and earlier reports. A synergistic relationship develops between activation of the innate immune system and the loss of organ barrier functions. Many complex factors, such as genetics, physical agents, mediators in the development of organ failure both in asthma, sinusitis, stress, depression and trauma, leading to posttraumatic organ failure. Asthma and sepsis, a common condition encountered in hospital environments remains an important cause of death at intensive care units where allergists/immunologists and otolaryngologists are frequently consulted. The patient's immune surveillance could fail to eliminate the pathogen, allowing it to spread and there is a proinflammatory mediator release with inappropriate activation. Conclusion This review discussed chronic rhinosinusitis, sinusitis related to trauma, the innate and adaptive immunology, NF-kappa B related to inflammation, sepsis, complement, inflammation, reactive oxygen species, asthma pathogenesis, and asthma in the elderly, oxidative stress, depression, seasonal variation and vitamin D, cytokines, genetic susceptibility related to sepsis, hereditary angioedema related to trauma and stress.

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