Previtamin D3 Research Articles

Determination of vitamin D3 content in cod liver oil using column-switching technique.

To develop a two-dimensional liquid chromatography method to determine the content of vitamin D3 in cod liver oil preparations. The samples were prepared by saponification and extraction, and the content of vitamin D3 was determined by two-dimensional liquid chromatography with dual-pump-single-valve switching dual detectors. The chromatographic column, capture device, and detection wavelength were optimized; the linearity, system suitability, recovery rate, repeatability and sample stability of the method were investigated, and further validated in actual sample determination. A column switching two-dimensional chromatography method was developed. In the first dimensional chromatography, an Agilent PoroShell SB-C8 (50 mm×4.6 mm, 2.7 μm) column was used, and acetonitrile-water was used as mobile phase and gradiently eluted at a flow rate of 1.0 mL/min, the detection wavelength was 264 nm. An Agilent Zorbax SB-C18 (150 mm×3.0 mm,1.8 μm) column was used in the second dimensional chromatography, and acetonitrile was used as mobile phase at a flow rate of 0.42 mL/min, the detection wavelength was 264 nm. In determining content of Vitamin D3, there was a good linear relationship in the concentration range and the system suitability, recovery rate, repeatability and sample stability all met the verification requirements. The developed two-dimensional liquid chromatography method in the study is accurate, reproducible and simple, it can simultaneously separate pre-vitamin D3, trans-vitamin D3, vitamin D3, and tachysterol3, the baseline separation was achieved, indicating that it is worth promoting for application.

Modeling of Biologically Effective Daily Radiant Exposures over Europe from Space Using SEVIRI Measurements and MERRA-2 Reanalysis

Ultraviolet solar radiation at the Earth’s surface significantly impacts both human health and ecosystems. A biologically effective daily radiant exposure (BEDRE) model is proposed for various biological processes with an analytical formula for its action spectrum. The following processes are considered: erythema formation, previtamin D3 synthesis, psoriasis clearance, and inactivation of SARS-CoV-2 virions. The BEDRE model is constructed by multiplying the synthetic BEDRE value under cloudless conditions by a cloud modification factor (CMF) parameterizing the attenuation of radiation via clouds. The CMF is an empirical function of the solar zenith angle (SZA) at midday and the daily clearness index from the Spinning Enhanced Visible and Infrared Imager (SEVIRI) measurements on board the second-generation Meteosat satellites. Total column ozone, from MERRA-2 reanalysis, is used in calculations of clear-sky BEDRE values. The proposed model was trained and validated using data from several European ground-based spectrophotometers and biometers for the periods 2014–2023 and 2004–2013, respectively. The model provides reliable estimates of BEDRE for all biological processes considered. Under snow-free conditions and SZA < 45° at midday, bias and standard deviation of observation-model differences are approximately ±5% and 15%, respectively. The BEDRE model can be used as an initial validation tool for ground-based UV data.

Unraveling the Catalytic Mechanism of β-Cyclodextrin in the Vitamin D Formation.

Previous experimental studies have shown that the isomerization reaction of previtamin D3 (PreD3) to vitamin D3 (VitD3) is accelerated 40-fold when it takes place within a β-cyclodextrin dimer, in comparison to the reaction occurring in conventional isotropic solutions. In this study, we employ quantum mechanics-based molecular dynamics (MD) simulations and statistical multistructural variational transition state theory to unveil the origin of this acceleration. We find that the conformational landscape in the PreD3 isomerization is highly dependent on whether the system is encapsulated. In isotropic media, the triene moiety of the PreD3 exhibits a rich torsional flexibility. However, when encapsulated, such a flexibility is limited to a more confined conformational space. In both scenarios, our calculated rate constants are in close agreement with experimental results and allow us to identify the PreD3 flexibility restriction as the primary catalytic factor. These findings enhance our understanding of VitD3 isomerization and underscore the significance of MD and environmental factors in biochemical modeling.

Long-term vitamin D insufficiency and associated risk factors for paediatric burns patients

The most recognised role of vitamin D in the body is for calcium absorption, and sufficiency is defined as a vitamin D blood serum level greater than 20 ng/mL (50 nmol/L). In growing children, hypovitaminosis D is associated with bone and muscle weakness, fractures, and osteoporosis. Burns patients are at a greater risk of low vitamin D levels due to lack of ultraviolet rays reaching the skin during prolonged hospital admission and sun avoidance post-burn injury. This study aimed to identify any individual, seasonal or burn injury characteristics in paediatric patients that were associated with low total vitamin D levels. Three different vitamin D metabolites were analysed to identify if, and where, in the synthesis pathway any insufficiencies may be occurring. Liquid Chromatography Mass Spectrometry (LCMS) was used to concurrently assess vitamin D3 (25OHD3 or Calcifediol), its epimer (3epi-25(OH)D3), and its precursor Pre Vitamin D3 (Cholecalciferol), in the plasma from 193 Australian paediatric burn patients, compared to 46 healthy controls. The results indicated that 61 % of healthy controls and up to 76 % of all burn patients had below normal clinical ranges of Total 25OHD3 (25(OH)D3 + 3epi-25(OH)D3). However, there were no significant differences between patient groups (control, acute, scarring, and reconstructive). The season of sample collection contributed significantly to total vitamin D levels but patients who were undergoing reconstructive surgery 1–17 years post-burn had consistently low vitamin D levels across all seasons. Routine screening, dietary monitoring, and potential supplementation of vitamin D in the burns population is recommended as it may impact recovery, growth and development of the child post-burn.

Measurements of biologically effective solar radiation using erythemal weighted broadband meters.

In this paper, we describe conversion factors (CF) for the calculation of biologically effective irradiances (BEI) from erythemal irradiance for three effects: photosynthesis of previtamin D3, psoriasis healing, and inactivation of the SARS-Cov-2 virions. CFs were empirically derived from measurements of spectral solar ultraviolet (UV) radiation during all sky conditions at four mid-latitude sites in the Northern Hemisphere, namely Aosta, Belsk, Reading, and San Diego. These CFs were found to depend on solar zenith angle (SZA) and total column ozone, but are largely independent (within ± 5% for SZA < 60°) of local conditions such as surface albedo, visibility and other local atmospheric patterns. The values of these empirical CFs are consistent with analytical CFs derived with radiative transfer calculations (model FastRT) for clear-sky and overcast conditions. To validate these analytical CFs, one-hour radiant exposures for the three biological effects were calculated from erythemal measurements at Reading between 2012 and 2021 and compared with similar exposures calculated directly from the spectral UV measurements. The two datasets agreed within 10% for SZA < 65°, demonstrating the utility of the conversion method. These results suggest that the proposed analytical CFs can be used with confidence to estimate radiant exposures for the three biological effects from measurements of the UV Index at any northern mid-latitude site.

Photoprotective Steering of Previtamin D3 Photochemistry by Phenylalanine in Solution

Provitamin D3 is the biological precursor to naturally formed vitamin D3 in humans, and its conversion is initiated via photoexcitation by near ultraviolet light. Following an initial photolysis, the primary intermediate, known as previtamin D3, is prone to light-induced isomerization or recyclization, which creates byproducts that limit the desired final thermal conversion to vitamin D3. The branching of the photochemical reaction is highly wavelength-dependent, whereby excitation toward the blue edge of the provitamin D3 absorption spectrum tends to terminate the reaction with the most undesired tachysterol byproduct and the lowest previtamin D3 concentration. In this work, the influence of introducing the natural amino acid phenyalanine as an excitation energy donor to the photochemical reaction is investigated. We find that the incorporation of phenylalanine into provitamin D3 solution results in greater intermediate concentrations and prolonged lifetimes of the desired previtamin D3 while simultaneously reducing the final concentration of tachysterol when exposing the solution to wavelengths at the blue edge of the provitamin D3 spectrum. The results, coupled with quantum chemical analysis, suggest that phenylalanine indeed helps to funnel energy from shorter wavelengths more effectively into the provitamin D3 precursor, while simultaneously screening those wavelengths from direct excitation, which otherwise leads to enhanced concentrations of tachysterol byproduct at the expense of previtamin D3.

Combination of a solid phase extraction and a two-dimensional LC-UV method for the analysis of vitamin D3 and its isomers in olive oil

The current HPLC methods for the quantification of vitamin D3 (VitD3) and its two isomers previtamin D3 (PreVitD3) and trans-vitamin D3 (trans-VitD3) in olive oil preparations present some limitations mainly due to peak overlapping of the oily matrix components with the compounds of interest. The use of two-dimensional liquid chromatography (2D-LC) with different retention mechanism can reach higher resolving power thus allowing the analysis of complex samples.The present paper proposes a new alternative method including a solid phase extraction sample preparation step and a two-dimensional liquid chromatographic analysis using routine instrumentation, fitting the needs of quality assurance and quality control laboratories of pharmaceutical companies. The extraction protocol was demonstrated to provide a clean-up of the sample and a quantitative recovery of the species of interest. The 2D method proved its suitability in the isolation of vitamins from oil components in the first dimension and the separation and quantification of the analytes in the second dimension thanks to the orthogonal selectivities of phenyl and porous graphitic carbon (PGC) stationary phases.The method was validated following ICH guidelines and possesses an adequate sensitivity to quantify the impurity trans-VitD3 in pharmaceuticals considering the limits imposed by regulatory agencies. The applicability of the phenyl x PGC 2D-LC-UV method to quality control of medicinal products based on VitD3 in olive oil was confirmed by the successful quantification of vitamins in olive oil formulations.

The Over-Irradiation Metabolite Derivative, 24-Hydroxylumister-ol3, Reduces UV-Induced Damage in Skin.

The hormonal form of vitamin D3, 1,25(OH)2D3, reduces UV-induced DNA damage. UV exposure initiates pre-vitamin D3 production in the skin, and continued UV exposure photoisomerizes pre-vitamin D3 to produce "over-irradiation products" such as lumisterol3 (L3). Cytochrome P450 side-chain cleavage enzyme (CYP11A1) in skin catalyzes the conversion of L3 to produce three main derivatives: 24-hydroxy-L3 [24(OH)L3], 22-hydroxy-L3 [22(OH)L3], and 20,22-dihydroxy-L3 [20,22(OH)L3]. The current study investigated the photoprotective properties of the major over-irradiation metabolite, 24(OH)L3, in human primary keratinocytes and human skin explants. The results indicated that treatment immediately after UV with either 24(OH)L3 or 1,25(OH)2D3 reduced UV-induced cyclobutane pyrimidine dimers and oxidative DNA damage, with similar concentration response curves in keratinocytes, although in skin explants, 1,25(OH)2D3 was more potent. The reductions in DNA damage by both compounds were, at least in part, the result of increased DNA repair through increased energy availability via increased glycolysis, as well as increased DNA damage recognition proteins in the nucleotide excision repair pathway. Reductions in UV-induced DNA photolesions by either compound occurred in the presence of lower reactive oxygen species. The results indicated that under in vitro and ex vivo conditions, 24(OH)L3 provided photoprotection against UV damage similar to that of 1,25(OH)2D3.

Stratospheric ozone, UV radiation, and climate interactions

This assessment provides a comprehensive update of the effects of changes in stratospheric ozone and other factors (aerosols, surface reflectivity, solar activity, and climate) on the intensity of ultraviolet (UV) radiation at the Earth’s surface. The assessment is performed in the context of the Montreal Protocol on Substances that Deplete the Ozone Layer and its Amendments and Adjustments. Changes in UV radiation at low- and mid-latitudes (0–60°) during the last 25 years have generally been small (e.g., typically less than 4% per decade, increasing at some sites and decreasing at others) and were mostly driven by changes in cloud cover and atmospheric aerosol content, caused partly by climate change and partly by measures to control tropospheric pollution. Without the Montreal Protocol, erythemal (sunburning) UV irradiance at northern and southern latitudes of less than 50° would have increased by 10–20% between 1996 and 2020. For southern latitudes exceeding 50°, the UV Index (UVI) would have surged by between 25% (year-round at the southern tip of South America) and more than 100% (South Pole in spring). Variability of erythemal irradiance in Antarctica was very large during the last four years. In spring 2019, erythemal UV radiation was at the minimum of the historical (1991–2018) range at the South Pole, while near record-high values were observed in spring 2020, which were up to 80% above the historical mean. In the Arctic, some of the highest erythemal irradiances on record were measured in March and April 2020. For example in March 2020, the monthly average UVI over a site in the Canadian Arctic was up to 70% higher than the historical (2005–2019) average, often exceeding this mean by three standard deviations. Under the presumption that all countries will adhere to the Montreal Protocol in the future and that atmospheric aerosol concentrations remain constant, erythemal irradiance at mid-latitudes (30–60°) is projected to decrease between 2015 and 2090 by 2–5% in the north and by 4–6% in the south due to recovering ozone. Changes projected for the tropics are ≤ 3%. However, in industrial regions that are currently affected by air pollution, UV radiation will increase as measures to reduce air pollutants will gradually restore UV radiation intensities to those of a cleaner atmosphere. Since most substances controlled by the Montreal Protocol are also greenhouse gases, the phase-out of these substances may have avoided warming by 0.5–1.0 °C over mid-latitude regions of the continents, and by more than 1.0 °C in the Arctic; however, the uncertainty of these calculations is large. We also assess the effects of changes in stratospheric ozone on climate, focusing on the poleward shift of climate zones, and discuss the role of the small Antarctic ozone hole in 2019 on the devastating “Black Summer” fires in Australia. Additional topics include the assessment of advances in measuring and modeling of UV radiation; methods for determining personal UV exposure; the effect of solar radiation management (stratospheric aerosol injections) on UV radiation relevant for plants; and possible revisions to the vitamin D action spectrum, which describes the wavelength dependence of the synthesis of previtamin D3 in human skin upon exposure to UV radiation.Graphical abstract

RF15 | PMON293 Metabolic activation of tachysterol to biologically active hydroxyderivatives that act on VDR, AhR, LXRs and PPARγ receptors

Abstract Absorption of ultraviolet B (UVB) radiation by the B ring of 7-dehydrocholesterol (7-DHC) leads to the transformation of 7-DHC to previtamin D3, which after absorption of additional UVB isomerizes to tachysterol3 (T3) and lumisterol3 (L3). Previously we demonstrated that CYP11A1 can hydroxylate the side chain of vitamin D3 (D3), 7-DHC and L3. Similarly CYP27A1 can hydroxylate the side chain of L3 to biologically active hydroxyderivatives. In a continuation of these studies, we report that CYP11A1 and CYP27A1 hydroxylate T3 to 20S(OH)T3 and 25(OH)T3, respectively, plus minor unidentified hydroxyderivatives. Both 20S(OH)T3 and 25(OH)T3were detected in the human epidermis and serum. T3 was also detected in human serum and was present at a concentration of 7.3±2.5 ng/ml. 20S(OH)T3 and 25(OH)T3 inhibited the proliferation of epidermal keratinocytes and dermal fibroblasts and stimulated the expression of differentiation and anti-oxidative genes in keratinocytes in a similar manner to 1,25-dihydroxyvitamin D3 . They acted on the vitamin D receptor (VDR) as demonstrated by image flow cytometry and the translocation of VDR-coupled GFP (VDR-GFP) from the cytoplasm to the nucleus of melanoma cells, as well as by the stimulation of CYP24A1 expression. Functional studies using a human aryl hydrocarbon receptor (AhR) reporter assay revealed marked activation of AhR by 20S(OH)T3, a smaller effect by 25(OH)T3 and only minimal activation by T3. The T3 hydroxyderivatives showed high affinity binding to the ligand binding domain (LBD) of the liver X receptor (LXR) α and β, and to the peroxisome proliferator-activated receptor γ (PPARg) in LanthaScreen TR-FRET coactivator assays. Molecular docking using crystal structures of the LBDs of VDR, AhR, LXRs and PPARγ revealed high docking scores for 20S(OH)T3 and 25(OH)T3, comparable to their previously characterized ligands. The scores for binding to the non-genomic site of the VDR were very low indicating a lack of interaction with hydroxy-T3 ligands. In conclusion, we have identified 20S(OH)T3 and 25(OH)T3 in the human epidermis and serum, identified CYP enzymes responsible for their production, demonstrated phenotypic effects on skin cells, and identified VDR, AhR, LXRs and PPARγ, and possibly RORs, as their genomic receptor targets. Thus CYP11A1, aside from its role in steroidogenesis, not only metabolizes vitamin D3, 7-DHC and L3 to biologically active metabolites, but also activates T3 to biologically active 20S(OH)T3. Similarly, CYP27A1, previously reported to act on L3, D3 and 7DHC, also activates T3 via hydroxylation at C25. We believe that these novel findings open new areas for future studies on the role of active forms of T3, not only in the skin, but also in systemic physiology and pathology. Presentation: Sunday, June 12, 2022 12:54 p.m. - 12:59 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Previtamin D action spectrum: Challenging CIE towards a standard

In 2006, CIE published a technical report on an action spectrum for the production of previtamin D3 in human skin. CIE procedure is to publish guidelines (e.g., an action spectrum) and let the community test them before moving to define a standard. The CIE previtamin D3 action spectrum has been in use for 15 years, and challenged on several occasions; a number of alternative action spectra have been suggested. To date (2021) no alternative action spectrum has shown clear advantages over the CIE version when tested against experimental outcomes. Thus, the CIE action spectrum remains widely used, but not fully accepted as best representing the photobiology in human skin leading to synthesis of vitamin D. We report on a CIE workshop designed to address the challenges to the CIE action spectrum, and explore alternative action spectra. The workshop concluded that the CIE action spectrum probably requires amendment, with several candidates for consideration in determining any changes. However, until there is a clear alternative, the CIE action spectrum should remain in use whilst ensuring full spectral information about sources of ultraviolet radiation. Thus, results are comparable between studies and can be recalculated to an updated action spectrum if necessary.

Sun-protective Properties of Technical Sportswear Fabrics 100% Polyester: The Influence of Moisture and Sweat on Protection against Different Biological Effects of Ultraviolet (UV) Radiation.

The use of technical sportswear is now widespread, but the degree of protection these fabrics offer against UV radiation is not known. We have analyzed the capacity of different types of technical sportswear fabrics to protect against different UV biological effects. A sample of 34 100% polyester t-shirts from different manufactures was classified by color, fabric structure, cover factor, and due to different tonalities, dark, and clear color. Ultraviolet protection factor was calculated according to UNE-EN13758. The protection factor for other biological effects as pre-vitamin D3 production, non-melanoma skin cancer, photoimmunosuppression, and photoaging was analyzed. The effects of moisture and sweat in protection were also evaluated. From the analyzed sample garments, more than 75% achieved an excellent protection value (protection factor 40-50+). Higher values were found in double-layer type (P < 0.05). Cover factor was the main determinant of biological protection factors with correlation coefficients of 0.81 for UPF (erythema), 0.77 for NMSC, and 0.63 for photoimmunosuppression. Water or sweat humidity saturation increased biological protection factors over a 20% (P < 0.05). The 83% of the fabrics analyzed showed less than 5% of transmittance with labeling as UVA protective elements. No effect of fabric color was found related to biological protection factors. The 100% polyester sports T-shirts of the analyzed sample offer general protection against UV for different biological effects that can be increased by humidity but no affected by fabric color.

Metabolic activation of tachysterol3 to biologically active hydroxyderivatives that act on VDR, AhR, LXRs, and PPARγ receptors.

CYP11A1 and CYP27A1 hydroxylate tachysterol3 , a photoproduct of previtamin D3 , producing 20S-hydroxytachysterol3 [20S(OH)T3 ] and 25(OH)T3 , respectively. Both metabolites were detected in the human epidermis and serum. Tachysterol3 was also detected in human serum at a concentration of 7.3 ± 2.5ng/ml. 20S(OH)T3 and 25(OH)T3 inhibited the proliferation of epidermal keratinocytes and dermal fibroblasts and stimulated the expression of differentiation and anti-oxidative genes in keratinocytes in a similar manner to 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ]. They acted on the vitamin D receptor (VDR) as demonstrated by image flow cytometry and the translocation of VDR coupled GFP from the cytoplasm to the nucleus of melanoma cells, as well as by the stimulation of CYP24A1 expression. Functional studies using a human aryl hydrocarbon receptor (AhR) reporter assay system revealed marked activation of AhR by 20S(OH)T3 , a smaller effect by 25(OH)T3 , and a minimal effect for their precursor, tachysterol3 . Tachysterol3 hydroxyderivatives showed high-affinity binding to the ligan-binding domain (LBD) of the liver X receptor (LXR) α and β, and the peroxisome proliferator-activated receptor γ (PPARγ) in LanthaScreen TR-FRET coactivator assays. Molecular docking using crystal structures of the LBDs of VDR, AhR, LXRs, and PPARγ revealed high docking scores for 20S(OH)T3 and 25(OH)T3 , comparable to their natural ligands. The scores for the non-genomic-binding site of the VDR were very low indicating a lack of interaction with tachysterol3 ligands. Our identification of endogenous production of 20S(OH)T3 and 25(OH)T3 that are biologically active and interact with VDR, AhR, LXRs, and PPARγ, provides a new understanding of the biological function of tachysterol3 .

Vitamin D esters are the major form of vitamin D produced by UV irradiation in mice.

The primary source of vitamin D3 for humans is that produced in skin by ultraviolet irradiation. Ultraviolet (UV) B (UVB, 280-310nm) light causes the isomerization of 7-dehydrocholesterol (7-DHC) to pre-vitamin D3 that is thermally isomerized to vitamin D3. In addition to free vitamin D3, it has been previously reported that esterified vitamin D3 is also found in the skin of rats irradiated with UVB. We found that a large fraction of the vitamin D3 precursor, 7-dehydrocholesterol is in the esterified form. Following UVB irradiation, vitamin D3 esters represent the majority of tissue vitamin D3, comprising approximately 80% in mice. Examination of vitamin D3 ester transport from skin in DBP-/- mice demonstrated that skin vitamin D3 ester content decreased only in the presence of DBP. No significant binding of vitamin D3 esters by serum was observed and no vitamin D3 esters were detectable in mouse serum after UVB treatment, indicating that the esters are hydrolyzed prior to transport into the circulation. The significance of vitamin D3 esters and their hydrolysis is the subject of current investigation.

Exploring Knowledge, Attitude and Practice (KAP) Towards Vitamin D among Arts and Commerce Students in Vistas Chennai

Introduction: Vitamin D is an essential nutrient and a group of fat-soluble pro-hormones with multiple functions in the body including bone health, regulation of serum calcium and phosphate levels, as well as roles in immune function, cell proliferation, differentiation, and apoptosis. The two major biologically inert precursors of vitamin D are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). Vitamin D3 is also formed when the skin is exposed to solar ultraviolet B and then converted to pre-vitamin D3 (Sunshine Vitamin). The severe vitamin D deficiency in adults and children’s causes softening of bones, muscle weakness and fractures.&#x0D; Aim: The aim of the study is to explore knowledge, Attitude and Practice towards Vitamin D among Arts &amp; Commerce students in Vels University Chennai.&#x0D; Methods and Materials: The study was a prospective cross-sectional, carried out in the department of arts and commerce students in VISTAS Chennai. The questionnaire then underwent a series of validation process that included content, face validity and exploratory part. Item response theory (IRT) analysis was utilized for the validation of the knowledge domain. Exploratory factor Analysis (EFA) used for attitude and practice validation. Institutional Ethical Committee (VISTAS-SPS/IEC/VI/2020/05) approval was obtained before conducting the study. Self-online questionnaires link was sent via mail after registration. The questionnaire was divided based on Knowledge, Attitude and Practice with 5 questions each. Completed questionnaires were reviewed, entered into a database (SPSS) and analysed using descriptive and inferential statistics.&#x0D; Results and Discussion: In our study, a total of 362 students were included where majority were males from first year commerce department around 18 to 19 years of age. Majority of the students had knowledge on vitamin D, attitude towards every day sun exposure and practice of using sun screens.&#x0D; Conclusion: Our study concluded that the students’ knowledge on vitamin D is good. There was an inconsistent practices towards managing its deficiency. Despite widespread, concern about vitamin D, still attitude and practice towards Vitamin D is yet to known for young generations.

Tanning-Elicited Variations in the Ultraviolet Absorption Spectra of the Cutaneous Tissues: Skin Photobiology and Photomedicine Implications.

When ultraviolet radiation is absorbed within the cutaneous tissues, it can trigger a number of phenomena that can have detrimental or beneficial consequences to an individual's health. Tanning is among the most visually noticeable of these phenomena. It may result in significant changes in skin pigmentation and thickness. These spectrally-dependent physiological responses, in turn, can elicit variations in the ultraviolet absorption profiles of the cutaneous tissues and, consequently, alter the occurrence of other ultraviolet-induced photobiological processes such as the breaking of DNA strands and the synthesis of previtamin D3. These tanning-elicited variations in the cutaneous tissues' absorption profiles is often tied to the increased presence of melanin throughout these tissues. However, during the tanning, shifts in the relative content of this pigment within certain skin layers can also be observed. In particular, the stratum basale, the innermost epidermal layer where melanogenesis takes place, can have its relative melanin content significantly reduced in comparison with other epidermal layers. Since the aforementioned photobiological phenomena are preferentially brought about within this layer, such pigmentation shifts may have a more pivotal role in skin photobiology than has been assumed to date. Accordingly, in this work, we investigate the impact of spectrally-dependent tanning-elicited physiological responses, with a particular focus on the inter-layer melanin distribution patterns, on the absorption profiles of the main cutaneous tissues. We also examine how variations in these absorption profiles may alter the outcomes of photo-triggered phenomena associated with the onset of different medical conditions. Our findings are expected to contribute to the advance of the current understanding about skin photobiology, which is indispensable for the success of photomedicine initiatives involving this highly complex organ.

A revised action spectrum for vitamin D synthesis by suberythemal UV radiation exposure in humans in vivo

Action spectra are important biological weighting functions for risk/benefit analyses of ultraviolet (UV) radiation (UVR) exposure. One important human benefit of exposure to terrestrial solar UVB radiation (∼295 to 315 nm) is the cutaneous synthesis of vitamin D3 that is initiated by the photoconversion of 7-dehydrocholesterol to previtamin D3 An action spectrum for this process that is followed by other nonphotochemical steps to achieve biologically active vitamin D3 has been established from ex vivo data and is widely used, although its validity has been questioned. We tested this action spectrum in vivo by full- or partial-body suberythemal irradiation of 75 healthy young volunteers with five different polychromatic UVR spectra on five serial occasions. Serum 25-hydroxyvitamin D3 [25(OH)D3] levels, as the most accurate measure of vitamin D3 status, were assessed before, during, and after the exposures. These were then used to generate linear dose-response curves that were different for each UVR spectrum. It was established that the previtamin D3 action spectrum was not valid when related to the serum 25(OH)D3 levels, as weighting the UVR doses with this action spectrum did not result in a common regression line unless it was adjusted by a blue shift, with 5 nm giving the best fit. Such a blue shift is in accord with the published in vitro action spectra for vitamin D3 synthesis. Thus, calculations regarding the risk (typically erythema) versus the benefit of exposure to solar UVR based on the ex vivo previtamin D3 action spectrum require revision.

Probing the Formation and Conformational Relaxation of Previtamin D3 and Analogues in Solution and in Lipid Bilayers.

The photosynthesis of vitamin D3 in mammalian skin results from UV-B irradiation of provitamin D3 (7-dehydrocholesterol, DHC) at ca. 290 nm. Upon return to the ground state, the hexatriene product, previtamin D3, undergoes a conformational equilibration between helical gZg and more planar tZg and tZt forms. The helical gZg forms provide a pathway for the formation of vitamin D3 via a [1,7]-sigmatropic hydrogen shift. Steady state photolysis and UV transient absorption spectroscopy are combined to explore the conformational relaxation of previtamin D3 formed from DHC in isotropic solution and confined to lipid bilayers chosen to model the biological cell membrane. The results are compared with measurements for two analogues: previtamin D2 formed from ergosterol (provitamin D2) and previtamin D3 acetate formed from DHC acetate. The resulting spectral dynamics are interpreted in the context of simulations of optical excitation energy and oscillator strength as a function of conformation. In solution, the relaxation dynamics and steady state product distributions of the three compounds are nearly identical, favoring tZg forms. When confined to lipid bilayers, the heterogeneity and packing forces alter the conformational distributions and enhance the population of a gZg conformer capable of vitamin D formation.

Vitamin D, Depressive Symptoms, and Covid-19 Pandemic

Since the COVID-19 outbreak, studies across diverse countries have strongly pointed toward the emergence of a mental health crisis, with a dramatic increase in the prevalence of depressive psychopathology and suicidal tendencies. Vitamin D deficiency has been associated with an increased risk of mental health problems as well as individual responses to stress. Studies have discussed the relationship between low serum vitamin D concentrations and depressive symptoms, suggesting that maintaining adequate concentrations of serum vitamin D seems to have a protective effect against it. Vitamin D was found to contribute to improved serotonergic neurotransmission in the experimental model of depression by regulating serotonin metabolism. The signaling of 1,25-dihydroxyvitamin D3, the active form of vitamin D, through vitamin D receptor (VDR) induces the expression of the gene of tryptophan hydroxylase 2 (TPH2), influences the expression of serotonin reuptake transporter (SERT) as well as the levels of monoamine oxidase-A (MAO-A), the enzyme responsible for serotonin catabolism. Vitamin D also presents a relevant link with chronobiological interplay, which could influence the development of depressive symptoms when unbalance between light-dark cycles occurs. In this Perspective, we discussed the significant role of vitamin D in the elevation of stress-related depressive symptoms during the COVID-19 pandemic. It is suggested that vitamin D monitoring and, when deficiency is detected, supplementation could be considered as an important healthcare measure while lockdown and social isolation procedures last during the COVID-19 pandemic.

Sun Exposure and Vitamin D.

Vitamin D is generally accepted in its importance on the regulation of calcium homeostasis and bone metabolism. Moreover, further health effects due to vitamin D are under discussion. In its effect, vitamin D is more like a hormone. In the classic view, a vitamin is an essential nutrient, which cannot be synthesized independently in the body. Besides nutrition, vitamin D will be produced in the body itself. The skin contains the provitamin D3 7-dehydrocholesterol, a precursor of vitamin D. Provitamin D3 will be photoconverted to previtamin D3 by UVB radiation that penetrates the skin superficially. In this way, the vitamin D metabolism will be started independent of the nutrition. In everyday life, this photosynthesis will be carried out due to the solar UVB radiation penetrating the uncovered skin. In the same spectral waveband range of UVB radiation, which causes the beneficial health effect of starting the vitamin D metabolism, the UVB radiation causes simultaneously acute and chronic harmful health effects as UV erythema (sunburn), skin aging and skin cancer. There is no vitamin D production in the skin without simultaneous DNA damage in the skin. Against this background, risks and benefits have to be balanced carefully.