scholarly journals Molecular actions of vitamin D in reproductive cell biology

Reproduction ◽  
2017 ◽  
Vol 153 (1) ◽  
pp. R29-R42 ◽  
Author(s):  
Kevin N Keane ◽  
Vinicius F Cruzat ◽  
Emily K Calton ◽  
Prue H Hart ◽  
Mario J Soares ◽  
...  

Vitamin D (VitD) is an important secosteroid and has attracted attention in several areas of research due to common VitD deficiency in the population, and its potential to regulate molecular pathways related to chronic and inflammatory diseases. VitD metabolites and the VitD receptor (VDR) influence many tissues including those of the reproductive system. VDR expression has been demonstrated in various cell types of the male reproductive tract, including spermatozoa and germ cells, and in female reproductive tissues including the ovaries, placenta and endometrium. However, the molecular role of VitD signalling and metabolism in reproductive function have not been fully established. Consequently, the aim of this work is to review current metabolic and molecular aspects of the VitD–VDR axis in reproductive medicine and to propose the direction of future research. Specifically, the influence of VitD on sperm motility, calcium handling, capacitation, acrosin reaction and lipid metabolism is examined. In addition, we will also discuss the effect of VitD on sex hormone secretion and receptor expression in primary granulosa cells, along with the impact on cytokine production in trophoblast cells. The review concludes with a discussion of the recent developments in VitD–VDR signalling specifically related to altered cellular bioenergetics, which is an emerging concept in the field of reproductive medicine.

2021 ◽  
Vol 5 (6) ◽  
pp. 1746-1754
Author(s):  
Normann Steiner ◽  
Georg Göbel ◽  
Daniela Michaeler ◽  
Anna-Luise Platz ◽  
Wolfgang Prokop ◽  
...  

Abstract Monoclonal gammopathy of undetermined significance (MGUS), a premalignant condition, is associated with various chronic inflammatory rheumatic diseases (RDs) and is frequently observed as an incidental finding during routine work-up. The association of MGUS and chronic RDs is well established, but the impact of RDs on the risk of transformation into overt multiple myeloma (MM) has not been evaluated so far. MGUS patients diagnosed between January 2000 and August 2016 were identified and screened for concomitant RDs. RDs were grouped into antibody (Ab)-mediated RDs and non-Ab–mediated RDs (polymyalgia rheumatica, large-vessel giant cell arteritis, spondyloarthritis, and gout). Progression to MM was defined as a categorical (yes/no) or continuous time-dependent (time to progression) variable. Of 2935 MGUS patients, 255 (9%) had a concomitant RD. MGUS patients diagnosed with non-Ab–mediated RDs had a doubled risk of progression compared with those without a concomitant RD (hazard ratio, 2.1; 95% CI, 1.1-3.9; P = .02). These data translate into a 5-year risk of progression of 4% in MGUS patients without rheumatologic comorbidity, 10% in those with concomitant non-Ab–mediated RDS, and 2% in those with Ab-mediated RDs. By using the complex risk stratification model that includes myeloma protein (M-protein) concentration, immunoglobulin type, and level of free light chain ratio as variables, patients with non-Ab–mediated RDs (n = 57) had the highest risk for progression (hazard ratio, 6.8; 95% CI, 1.5-30.7; P = .01) compared with patients with Ab-mediated RDs (n = 77). Chronic inflammatory diseases have an impact on the risk of MGUS progressing into overt MM, with a doubled risk of transformation observed in patients with non-Ab–mediated RDs. Future research can elucidate whether comorbidities such as RDs should be included in currently applied prognostic MGUS scores.


2020 ◽  
Author(s):  
Hector Guadalajara ◽  
Jose Luis Muñoz de Nova ◽  
Saul Fernandez Gonzalez ◽  
Marina Yiasemidou ◽  
Maria Recarte Rico ◽  
...  

Abstract BackgroundAnecdotal evidence suggests that community infection control measures during the COVID-19 outbreak have modified the number and natural history of acute surgical inflammatory processes (ASIP - appendicitis, cholecystitis, diverticulitis and perianal abscesses) admissions. This study aims to evaluate the impact of the COVID-19 pandemic on the presentation and treatment ASIP and quantify the effect of COVID-19 infection on the outcomes of ASIP patients. MethodsThis was a multicentre, comparative study, whereby ASIP cases from March 14th to May 2nd 2019 acted as historical controls for the cohort of patients with the same pathology during the COVID-19 pandemic. Data regarding patient and disease characteristics as well as outcomes, were collected from sixteen centres in Madrid, and one in Seville (Spain).ResultsThe number of patients treated for ASIP in 2019 was 822 compared to 521 in 2020. This reduction occurs mainly in patients with mild cases, while the number of severe cases was similar. ConclusionsThe number of ASIP cases treated during the pandemic was reduced by more than one third mainly due to a dramatic reduction in mild cases. This also has represented a selection of severe cases. We also found a more conservative approach to the patients this year, non-justified by clinical circumstances.The positive COVID-19 status itself did not have a direct impact on either morbidity or mortality. This is an interesting finding which if confirmed through future research with a larger sample size of COVID-19 positive patients, can expedite the recovery phase of acute surgical services.


2021 ◽  
Vol 160 (6) ◽  
pp. S-98-S-99
Author(s):  
Anita Rao ◽  
Yueyue Yu ◽  
Jing Lu ◽  
Lei Lu ◽  
Yong-Guo Zhang ◽  
...  

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2536-2536
Author(s):  
Christian M. Capitini ◽  
Joanna L. Meadors ◽  
Monica M. Cho ◽  
Rimas J. Orentas ◽  
Crystal L. Mackall ◽  
...  

Abstract Abstract 2536 Methods to expand natural killer (NK) cells ex vivo for adoptive cell therapy are being explored to improve outcomes after allogeneic blood and marrow transplant (alloBMT). Artificial antigen presenting cells (aAPCs) can present cytokines and/or co-stimulatory molecules that can potentially improve expansion and activity. 4-1BBL (CD137L) has demonstrated mixed results on murine and human NK cells, but the impact on murine NK cell biology after alloBMT has not been explored. NK cells were harvested from either C57BL/6 (B6) or CB6F1 spleens and cultured ex vivo with a recombinant interleukin (IL)-15/IL-15 receptor alpha (Ra) complex in the presence or absence of a CD137L+ aAPC. Because IL-15 is typically presented in trans by IL-15Ra, the complex was utilized to potently increase agonist bioactivity. NK cells cultured with IL-15/IL-15Ra alone showed a peak of 20-fold expansion, but this expansion was decreased with the addition of CD137L+ aAPCs if the ratio of aAPC to NK cells was greater than 1:1. In the presence of IL-15/IL-15Ra, the impact of CD137L+ aAPCs on expression of the inhibitory receptors, Ly49C+I and activating receptor Ly49H was variable and strain dependent, with increased expression in B6 NK cells, but decreased expression in CB6F1 NK cells. The expression of major histocompatibility complex (MHC) class I was not affected in NK cells from either strain by the presence of CD137L+ aAPCs. The production of gamma interferon and tumor necrosis factor-a was robust in NK cells expanded by IL-15/IL-15Ra alone, but attenuated with the addition of CD137L+ aAPCs. Animal experiments showed that administration of NK cells expanded ex vivo with IL-15/IL-15Ra alone was well tolerated after T cell depleted MHC-mismatched alloBMT (CB6F1–>B6), but surprisingly the addition of CD137L+ aAPCs to cultures caused NK cells to induce GVHD-associated weight loss. In summary, IL-15/IL-15Ra expanded murine NK cells demonstrate increased cytokine production and do not cause toxicity when infused after alloBMT. The presence of CD137L+ aAPCs attenuated cytokine production and increased Ly49 receptor expression in NK cells from B6 mice. Remarkably, NK cells expanded by IL-15/IL-15Ra in the presence of CD137L+ aAPCs demonstrate increased propensity to cause GVHD. Ongoing studies are exploring the anti-tumor efficacy of IL-15/IL-15Ra expanded murine NK cells cultured in the presence and absence of CD137L. Disclosures: No relevant conflicts of interest to declare.


2012 ◽  
Vol 34 (1) ◽  
pp. 33-83 ◽  
Author(s):  
Christian M. Girgis ◽  
Roderick J. Clifton-Bligh ◽  
Mark W. Hamrick ◽  
Michael F. Holick ◽  
Jenny E. Gunton

Abstract Beyond its established role in bone and mineral homeostasis, there is emerging evidence that vitamin D exerts a range of effects in skeletal muscle. Reports of profound muscle weakness and changes in the muscle morphology of adults with vitamin D deficiency have long been described. These reports have been supplemented by numerous trials assessing the impact of vitamin D on muscle strength and mass and falls in predominantly elderly and deficient populations. At a basic level, animal models have confirmed that vitamin D deficiency and congenital aberrations in the vitamin D endocrine system may result in muscle weakness. To explain these effects, some molecular mechanisms by which vitamin D impacts on muscle cell differentiation, intracellular calcium handling, and genomic activity have been elucidated. There are also suggestions that vitamin D alters muscle metabolism, specifically its sensitivity to insulin, which is a pertinent feature in the pathophysiology of insulin resistance and type 2 diabetes. We will review the range of human clinical, animal, and cell studies that address the impact of vitamin D in skeletal muscle, and discuss the controversial issues. This is a vibrant field of research and one that continues to extend the frontiers of knowledge of vitamin D's broad functional repertoire.


Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1624
Author(s):  
Tomoka Ao ◽  
Junichi Kikuta ◽  
Masaru Ishii

Immune cells, including dendritic cells, macrophages, and T and B cells, express the vitamin D receptor and 1α-hydroxylase. In vitro studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, has an anti-inflammatory effect. Recent epidemiological evidence has indicated a significant association between vitamin D deficiency and an increased incidence, or aggravation, of infectious diseases and inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. However, the impact of vitamin D on treatment and prevention, particularly in infectious diseases such as the 2019 coronavirus disease (COVID-19), remains controversial. Here, we review recent evidence associated with the relationship between vitamin D and inflammatory diseases and describe the underlying immunomodulatory effect of vitamin D.


2016 ◽  
Vol 311 (5) ◽  
pp. F1047-F1062 ◽  
Author(s):  
David Granjon ◽  
Olivier Bonny ◽  
Aurélie Edwards

We developed a model of calcium homeostasis in the rat to better understand the impact of dysfunctions such as primary hyperparathyroidism and vitamin D deficiency on calcium balance. The model accounts for the regulation of calcium intestinal uptake, bone resorption, and renal reabsorption by parathyroid hormone (PTH), vitamin D3, and Ca2+itself. It is the first such model to incorporate recent findings regarding the role of the calcium-sensing receptor (CaSR) in the kidney, the presence of a rapidly exchangeable pool in bone, and the delayed response of vitamin D3synthesis. Accounting for two (fast and slow) calcium storage compartments in bone allows the model to properly predict the effects of bisphophonates on the plasma levels of Ca2+([Ca2+]p), PTH, and vitamin D3. Our model also suggests that Ca2+exchange rates between plasma and the fast pool vary with both sex and age, allowing [Ca2+]pto remain constant in spite of sex- and age-based hormonal and other differences. Our results suggest that the inconstant hypercalciuria that is observed in primary hyperparathyroidism can be attributed in part to counterbalancing effects of PTH and CaSR in the kidney. Our model also correctly predicts that calcimimetic agents such as cinacalcet bring down [Ca2+]pto within its normal range in primary hyperparathyroidism. In addition, the model provides a simulation of CYP24A1 inactivation that leads to a situation reminiscent of infantile hypercalcemia. In summary, our model of calcium handling can be used to decipher the complex regulation of calcium homeostasis.


1996 ◽  
Vol 316 (2) ◽  
pp. 361-371 ◽  
Author(s):  
Sylvia CHRISTAKOS ◽  
Mihali RAVAL-PANDYA ◽  
Roman P. WERNYJ ◽  
Wen YANG

The biologically active metabolite of vitamin D (cholecalciferol), i.e. 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is a secosteroid hormone whose mode of action involves stereospecific interaction with an intracellular receptor protein (vitamin D receptor; VDR). 1,25(OH)2D3 is known to be a principal regulator of calcium homeostasis, and it has numerous other physiological functions including inhibition of proliferation of cancer cells, effects on hormone secretion and suppression of T-cell proliferation and cytokine production. Although the exact mechanisms involved in mediating many of the different effects of 1,25(OH)2D3 are not completely defined, genomic actions involving the VDR are clearly of major importance. Similar to other steroid receptors, the VDR is phosphorylated; however, the exact functional role of the phosphorylation of the VDR remains to be determined. The VDR has been reported to be regulated by 1,25(OH)2D3 and also by activation of protein kinases A and C, suggesting co-operativity between signal transduction pathways and 1,25(OH)2D3 action. The VDR binds to vitamin D-responsive elements (VDREs) in the 5´ flanking region of target genes. It has been suggested that VDR homodimerization can occur upon binding to certain VDREs but that the VDR/retinoid X receptor (RXR) heterodimer is the functional transactivating species. Other factors reported to be involved in VDR-mediated transcription include chicken ovalbumin upstream promoter (COUP) transcription factor, which is involved in active silencing of transcription, and transcription factor IIB, which has been suggested to play a major role following VDR/RXR heterodimerization. Newly identified vitamin D-dependent target genes include those for Ca2+/Mg2+-ATPase in the intestine and p21 in the myelomonocytic U937 cell line. Elucidation of the mechanisms involved in the multiple actions of 1,25(OH)2D3 will be an active area of future research.


2020 ◽  
Vol 29 (4) ◽  
pp. 2097-2108
Author(s):  
Robyn L. Croft ◽  
Courtney T. Byrd

Purpose The purpose of this study was to identify levels of self-compassion in adults who do and do not stutter and to determine whether self-compassion predicts the impact of stuttering on quality of life in adults who stutter. Method Participants included 140 adults who do and do not stutter matched for age and gender. All participants completed the Self-Compassion Scale. Adults who stutter also completed the Overall Assessment of the Speaker's Experience of Stuttering. Data were analyzed for self-compassion differences between and within adults who do and do not stutter and to predict self-compassion on quality of life in adults who stutter. Results Adults who do and do not stutter exhibited no significant differences in total self-compassion, regardless of participant gender. A simple linear regression of the total self-compassion score and total Overall Assessment of the Speaker's Experience of Stuttering score showed a significant, negative linear relationship of self-compassion predicting the impact of stuttering on quality of life. Conclusions Data suggest that higher levels of self-kindness, mindfulness, and social connectedness (i.e., self-compassion) are related to reduced negative reactions to stuttering, an increased participation in daily communication situations, and an improved overall quality of life. Future research should replicate current findings and identify moderators of the self-compassion–quality of life relationship.


Author(s):  
Endy Gunanto ◽  
Yenni Kurnia Gusti

In this article we present a conceptual of the effect of cross culture on consumer behavior incorporating the impact of globalization. This conceptual idea shows that culture inûuences various domains of consumer behavior directly as well as through international organization to implement marketing strategy. The conceptual identify several factors such as norm and value in the community, several variables and also depicts the impact of other environmental factors and marketing strategy elements on consumer behavior. We also identify categories of consumer culture orientation resulting from globalization. Highlights of each of the several other articles included in this special issue in Asia region. We conclude with the contributions of the articles in terms of the consumer cultural orientations and identify directions for future research.


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