Search

The development of numerous drugs is often arrested at clinical testing stages, due to their unfavorable biopharmaceutical characteristics. It is the case of fenretinide (4-HPR), a second-generation retinoid, that demonstrated promising in vitro cytotoxic activity against several cancer cell lines. Unfortunately, response rates in early clinical trials with 4-HPR did not confirm the in vitro findings, mainly due to the low bioavailability of the oral capsular formulation that was initially developed. Capsular 4-HPR provided variable and insufficient drug plasma levels attributable to the high hepatic first-pass effect and poor drug water solubility. To improve 4-HPR bioavailability, several approaches have been put forward and tested in preclinical and early-phase clinical trials, demonstrating generally improved plasma levels and minimal systemic toxicities, but also modest antitumor efficacy. The challenge is thus currently still far from being met. To redirect the diminished interest of pharmaceutical companies toward 4-HPR and promote its further clinical development, this manuscript reviewed the attempts made so far by researchers to enhance 4-HPR bioavailability. A comparison of the available data was performed, and future directions were proposed. [ABSTRACT FROM AUTHOR]

Erythrodermic psoriasis (EP) is a rare and life‐threatening disease, the pathogenesis of which remains to be largely unknown. Metabolomics analysis can provide global information on disease pathophysiology, candidate biomarkers, and potential intervention strategies. To gain a better understanding of the mechanisms of EP and explore the serum metabolic signature of EP, we conducted an untargeted metabolomics analysis from 20 EP patients and 20 healthy controls. Furthermore, targeted metabolomics for focused metabolites were identified in the serum samples of 30 EP patients and 30 psoriasis vulgaris (PsV) patients. In the untargeted analysis, a total of 2992 molecular features were extracted from each sample, and the peak intensity of each feature was obtained. Principal component analysis (PCA), orthogonal partial least squares‐discriminant analysis (OPLS‐DA) revealed significant difference between groups. After screening, 98 metabolites were found to be significantly dysregulated in EP, including 67 down‐regulated and 31 up‐regulated. EP patients had lower levels of L‐tryptophan, L‐isoleucine, retinol, lysophosphatidylcholine (LPC), and higher levels of betaine and uric acid. KEGG analysis showed differential metabolites were enriched in amino acid metabolism and glycerophospholipid metabolism. The targeted metabolomics showed lower L‐tryptophan in EP than PsV with significant difference and L‐tryptophan levels were negatively correlated with the PASI scores. The serum metabolic signature of EP was discovered. Amino acid and glycerophospholipid metabolism were dysregulated in EP. The metabolite differences provide clues for pathogenesis of EP and they may provide insights for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background High-resolution metabolomics (HRM) is an innovative tool to study challenging infectious diseases like leprosy, where the pathogen cannot be grown with standard methods. Here, we use HRM to better understand associations between disease manifestations, nutrition, and host metabolism. Methods From 2018 to 2019, adults with leprosy and controls were recruited in Minas Gerais, Brazil. Plasma metabolites were detected using an established HRM workflow and characterized by accurate mass, mass to charge ratio m/z and retention time. The mummichog informatics package compared metabolic pathways between cases and controls and between multibacillary (MB) and paucibacillary (PB) leprosy. Additionally, select individual metabolites were quantified and compared. Results Thirty-nine cases (62% MB and 38% PB) and 25 controls were enrolled. We found differences (P <.05) in several metabolic pathways, including fatty acid metabolism, carnitine shuttle, retinol, vitamin D3, and C-21 steroid metabolism, between cases and controls with lower retinol and associated metabolites in cases. Between MB and PB, leukotrienes, prostaglandins, tryptophan, and cortisol were all found to be lower in MB (P <.05). Discussion Metabolites associated with several nutrient-related metabolic pathways appeared differentially regulated in leprosy, especially MB versus PB. This pilot study demonstrates the metabolic interdependency of these pathways, which may play a role in the pathophysiology of disease. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion There is a dearth of effective treatments to counter retinol‐induced skin irritation.This study aimed to investigate the efficacy of three potential mitigants: (i) phytosteryl/octyldodecyl lauroyl glutamate (PLG), (ii) a physiologic lipid mixture (PLM) comprised of ceramide three and cholesterol, and (iii) niacinamide, in ameliorating irritation instigated by retinol.An occlusive human patch test, spanning 5 days, was undertaken on 18 Chinese participants aged between 23 and 40. It was designed as a randomized, double‐blind, and vehicle‐controlled study. Clinician erythema assessment (CEA) and instrumental evaluations were employed pre and post‐test. Subsequently, a 4‐week consumer in‐use test, randomized and double‐blind in nature, was executed to substantiate the soothing effects of PLG.Data from CEA and bioengineering assessments revealed that, in comparison to the vehicle control, both 2% PLG and 5% PLM notably curbed retinol‐induced skin erythema and inflammation. Notably, PLG outperformed PLM. Conversely, 3% niacinamide did not offer relief against retinol‐induced discomfort. The subsequent consumer in‐use test affirmed that treatments with 2% PLG were better tolerated than those with the vehicle alone.To the best of our knowledge, this study represents the first confirmation that physiologic lipids effectively mitigate retinol‐induced irritation. Given their capacity to counter retinol‐induced irritation, physiologic lipids, particularly PLG, are recommended for incorporation in retinol regimens. Additionally, the Visia‐CR a* value can serve as a robust objective measure for interpreting patch test outcomes. [ABSTRACT FROM AUTHOR]

Bakuchiol (BAK) is a natural phenolic meroterpene isolated from the fruits of Psoralea corylifolia that exhibits a variety of pharmacological effects, including anti-aging, anti-microbial, hyperpigmentation, and anti-cancer activities. Furthermore, the usage of BAK is gaining popularity amongst researchers since it does not induce the same negative reactions as topical retinoids, such as blistering and scaling, allowing greater adoption for individuals with sensitive skin. The growing trend towards "clean" skin care products, as well as the hunt for retinoid substitutes, has elevated BAK to the status of a "must have" component in cosmetology and dermatology. Although, the pathogenesis of BAK is not completely understood yet it is known to play a pivotal role in acting as a scavenger of free radicals thus exerting an antioxidant effect which is helpful in the management of various skin disorders. It also regulates the expression of collagen and extracellular matrix synthesis enzymes which aids in reversing the signs of photo-aging. Moreover, natural sources of BAK are also being employed in traditional Chinese and Indian medicines due to their antitumor and anti-inflammatory properties. In this review we have provided the occurrence, extraction, isolation methods and structure-activity relationships of BAK. Moreover, this review discusses the pharmacological benefits of BAK, its novel and marketed formulations and a brief overview of its patents. [ABSTRACT FROM AUTHOR]

Adult acne vulgaris affects up to 43–51% of individuals. While there are numerous treatment options for acne including topical, oral, and energy-based approaches, benzoyl peroxide (BPO) is a popular over the counter (OTC) treatment. Although BPO monotherapy has a long history of efficacy and safety, it suffers from several disadvantages, most notably, skin irritation, particularly for treatment naïve patients. In this prospective, randomized, controlled, split-face study, we evaluated the comparative efficacy, safety, and tolerability of a novel 3-step azelaic acid, salicylic acid, and graduated retinol regimen versus a common OTC BPO-based regimen over 12 weeks. A total of 37 adult subjects with self-reported mild to moderate acne vulgaris were recruited. A total of 21 subjects underwent a 2-week washout period and completed the full study with 3 dropping out due to product irritation from the BPO routine, and 13 being lost to follow-up. Detailed tolerability surveys were conducted at Week 4. Additional surveys on tolerability and product preferences were collected monthly, at Week 4, Week 8, and Week 12. A blinded board-certified dermatologist objectively scored the presence and type of acne lesions (open or closed comedones, papules, pustules, nodules, and cysts) at baseline, Week 4, Week 8, and Week 12. Patients photographed themselves and uploaded the images using personal mobile phones. Detailed Week 4 survey results showed across 25 domains of user-assessed product performance, the novel routine outperformed the BPO routine in 19 (76%) which included domains in preference (e.g. "I would use this in the future) and performance ("my skin improved" and "helped my acne clear up faster"). Users of the novel routine reported less facial redness, itching, and burning, though differences did not reach statistical significance. In terms of efficacy, both products performed similarly, reducing total acne lesions by 36% (novel routine) and 40% (BPO routine) by Week 12. Overall, accounting for user preferences and tolerability the novel routine was more preferred than the BPO routine in 79% of domains (22/28). Differences in objective acne lesion reduction were not statistically significant (p = 0.97). In a randomized split-face study, a 3-step azelaic acid, salicylic acid, and graduated retinol regimen delivered similar acne lesion reduction, fewer user dropouts, greater user tolerability, and higher use preference compared to a 3-step BPO routine based in a cohort of participants with mild-to-moderate acne vulgaris. [ABSTRACT FROM AUTHOR]

Objective To explore the relationship between retinol and TTR protein, and to provide ideas for preventing Hereditary vitreous amyloidosis (HVA). Methods Twenty Gly83Arg mutant mice were constructed and bred (reference construction)as the mutant group. After the irregular turbidity in the vitreous of the mutant mice eyeball was observed under slit lamp, the lens camera was used for photography, and B 一 ultrasound examination was conducted, and white clump 一 like turbidity was found in the posterior ocular region. After the turbidity in the vitreous cavity of the mice was confirmed, the mice were killed by cervical vertebrae dislocation, and DNA in liver cells was extracted and sequenced to confirm the successful construction of mutant mice. At the same time, 20 wild type C57BL/6 mice were fed as the control group, 4 mice in the mutant group and 4 mice in the control group were randomly selected from the number table, and the retinol concentration was determined by high performance liquid chromatography combined with mass spectrometry. Three mice in the mutant group and three mice in the control group were selected from a random number table. After grinding the eyeball tissues, RNA and protein were extracted. TTR gene mRNA expression, SDS 一 PAGE protein gel color development was detected by fluorescent quantitative PCR, and TTR gene protein expression was detected by Western Blot. The difference at P < 0. 05 was statistically. [ABSTRACT FROM AUTHOR]

The encapsulation of retinol within silica microparticles has emerged as a promising opportunity in the realm of cosmetic and pharmaceutical formulations, driven by the need to reinforce the photoprotection and oxidation stability of retinol. This work examines the process of encapsulating retinol into silica microparticles. The association efficiency, microparticle size, molecular structure, morphology, oxidation, and release profile, as well as biocompatibility and skin sensitization, were evaluated. Results showed that 0.03% of retinol and 9% of emulsifier leads to an association efficiency higher than 99% and a particle size with an average of 5.2 µm. FTIR results indicate that there is an association of retinol with the silica microparticles, and some may be on the surface. Microscopy indicates that when association happens, there is less aggregation of the particles. Oxidation occurs in two different phases, the first related to the retinol on the surface and the second to the associated retinol. In addition, a burst release of up to 3 h (30% free retinol, 17% associated retinol) was observed, as well as a sustained release of 44% of retinol up to 24 h. Encapsulation allowed an increase in the minimal skin cytotoxic concentrations of retinol from 0.04 μg/mL to 1.25 mg/mL without skin sensitization. Overall, retinol is protected when associated with silica microparticles, being safe to use in cosmetics and dermatology. [ABSTRACT FROM AUTHOR]

The high toxicity of mercury (Hg) poses a danger to the environment and humans, but studies of the concentration of this metal in organisms of terrestrial ecosystems are few. Ecotoxicologists also pay little attention to studying the role of antioxidant vitamins in protecting cells from toxic metals. The Republic of Karelia is one of the northwestern regions of Russia, the biogeochemical features of which can contribute to an increase in the mobility and bioavailability of Hg in food chains. The purpose of the work was to determine the concentration of Hg in the liver, kidneys, muscle and hair of ungulate mammals of the Republic of Karelia (wild boar Sus scrofa L. and moose Alces alces L.) and to analyze the relationship between the level of this toxic metal and the content of low molecular-weight antioxidants—reduced glutathione, retinol and α-tocopherol. Species and tissue-specific of the studied parameters in wild boars and moose are noted. The observations discovered by other researchers that omnivorous species accumulate more Hg in their tissues compared to herbivores, and also that this toxic metal is predominantly accumulated in the kidneys, while muscles contain a minimal amount, have been confirmed. Hg concentrations in most samples of liver and kidney of wild boars and in all samples of the same organs of moose were within the limits recorded for domestic pigs and deer, respectively. The levels of Hg we recorded in the tissues and hair of wild boars and moose were generally comparable to or lower than the levels of this metal noted in animals from other regions of Russia and other countries of the world. In wild boars and moose of Karelia, no statistically significant relationships were found between the Hg level and the content of the studied antioxidants in the internal organs. Moose were characterized by a higher content of α-tocopherol in the body than wild boars, which is a feature of this type of herbivorous ungulate mammal. The results of the study indicate a relatively low level of mercury pollution in terrestrial ecosystems in Karelia. [ABSTRACT FROM AUTHOR]

Background. The aim: to assess the level of retinol, and tocopherol in the oral fluid of children with progressive myopia. Materials and methods. We examined 34 children (68 eyes) with mild myopia included in group I. It was divided into two subgroups: Ia — 16 children (32 eyes) with a progressive course of myopia, and Ib — 18 children (36 eyes) with a stable course of myopia. The control group consisted of 18 conditionally healthy children (36 eyes). A standard eye examination was carried out: visometry, autorefractokeratometry before and after cycloplegia, biomicroscopy, ophthalmoscopy. The level of retinol, and tocopherol in the oral fluid was determined by the enzyme immunoassay. Results. In children with a progressive course of myopia, the retinol indicator is on average 1.2 times lower than in those with a stable course of myopia (p < 0.05), and also on average 2.3 times lower than in controls (р < 0.05). At the same time, in children with a progressive course, the level of tocopherol was 1.3 times lower than in patients with a stable myopia (p < 0.05). In the subgroup with a progressive course, this indicator was 3 times lower than in children without ophthalmic pathology (p < 0.05). Correlation analysis showed a moderate reliable inverse relationship between the level of retinol and the progression of myopia (r= –0.43; p < 0.05). A moderate reliable inverse relationship was found between the level of tocopherol and the progression of myopia (r = –0.47; p < 0.05). Correlation analysis demonstrated a reliable direct relationship between the level of retinol and tocopherol (r = 0.89; p < 0.05). The optimal value of the cut-off threshold, which provides the maximum sensitivity and specificity, is ≤ 99.602 ng/ml (р < 0.05) for the indicator of retinol in the oral fluid of children with progressive myopia. Conclusions. In pediatric patients with a progressive course of myopia, the level of retinol in the oral fluid is on average 2.3 times lower and the level of tocopherol is 3 times lower than that of children without ophthalmic pathology (p < 0.05). An inverse correlation was found between the levels of retinol and tocopherol and the progressive course of myopia. It was revealed that determining the level of retinol and tocopherol in the oral fluid allows diagnosing the progressive course of myopia, with retinol levels ≤ 99.602 ng/ml, tocopherol ≤ 5.129 ng/ml (p < 0.001). [ABSTRACT FROM AUTHOR]

This work evaluated the influence of vitamin A on performance, organ weight, and bone and skin characteristics in broilers (Cobb 500) at 21 and 42 days of age. A total of 1920 chickens were distributed in a randomised design, considering six vitamin A supplementation levels (0, 6000, 16,000, 26,000, 36,000, and 46,000 IU kg−1), with 16 replicates and 20 chickens per experimental unit, established due to rising the range of vitamin levels observed in the literature to evaluate the effect of vitamin A on broilers. At 22 days, half of the replicates from each treatment continued receiving the initial diet, and the other eight repetitions received diets without vitamin A (0 IU kg−1) until 42 days. The level of vitamin A influenced feed intake (FI) and body weight gain (BWG) until 21 days for all treatments. Broilers at 21 days of age had a more significant BWG at a vitamin A supplementation level of 28,209 IU kg−1. At 42 days, vitamin A influenced the BWG and FI of broilers at treatments that were not supplemented after 21 days. Treatments supplemented up to 42 days showed quadratic responses to vitamin A for BWG, FI, and feed conversion. The vitamin A levels influenced the relative weights of the small intestine, pancreas, gizzard, abdominal fat, Seedor index, and breaking strength at 42 days, where the adequate supplementation of vitamin A improved these characteristics in broilers. Vitamin A supplementation from 22 to 42 days old did not affect broiler performance. An increased BWG was obtained when vitamin A supplementation occurred until 42 days, with supplementation of 29,375 IU kg−1 and a lower response of feed conversion with the addition of 27,775 IU kg−1. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the association between dietary intake of preformed vitamin A (VA) and pro-VA carotenoids and serum retinol and carotenoid concentrations among 36–59-month-old children in a rural area in Burkina Faso. Methods: Two community-based cross-sectional studies were conducted in a rural area of Burkina Faso and included 115 children aged 36–59 months. Dietary intake of preformed VA and pro-VA was assessed directly by 24-h dietary recall. Serum retinol and carotenoid (α- and β-carotene, and β-cryptoxanthin) concentrations were measured. The associations between serum retinol and carotenoid concentrations and their respective dietary intake were assessed by multiple linear regression. Results: Geometric mean [95% CI] adjusted serum retinol concentration in children was 0.86 [0.81; 0.92] µmol/L. The prevalence of low adjusted serum retinol concentration (< 0.7 µmol/L) was 26.8%. Geometric mean [95% CI] serum carotenoid concentrations were: α-carotene (0.03 [0.02; 0.03] µmol/L), β-carotene (0.14 [0.12; 0.16] µmol/L), and β-cryptoxanthin (0.17 [0.15; 0.21] µmol/L). Dietary intakes of α- and β-carotene and adjusted serum retinol and α-carotene concentrations were significantly higher during the rainy season. In multiple linear regressions, no associations were found between dietary intakes of preformed VA and pro-VA carotenoids and serum retinol and carotenoid concentrations in children aged 36–59 months in Burkina Faso. There was no effect of season on the associations between preformed VA and pro-VA carotenoids intake and serum retinol and carotenoid concentrations. Conclusions: This study shows that dietary intakes of preformed VA and pro-VA carotenoids based on 24-h dietary recall method cannot be used as proxy of serum retinol and carotenoid concentrations in this population. Trial registration: The study was registered retrospectively (22 March 2018) as a clinical trial with the Pan African Clinical Trials Registry (Cochrane South Africa; PACTR201803002999356). [ABSTRACT FROM AUTHOR]

Oxidative stress is caused by an imbalance between the production of harmful oxygen molecules and the body's ability to repair their detrimental implications, leading to reduced growth rates, increased disease susceptibility, and decreased reproductive performance in animals. Vitamin A, comprising retinol, retinal, and retinoic acid, is crucial for normal growth, reproduction, and vision. Vitamin A possesses antioxidant properties by directly scavenging reactive oxygen species, boosting antioxidant enzyme activity, and promoting antioxidant defence mechanisms. Numerous studies have shown that livestock with adequate levels of vitamin A in their diet experience reduced oxidative stress compared to those with vitamin A deficiency. Moreover, vitamin A supplementation can mitigate oxidative stress in animals exposed to stressful conditions like heat stress. Adequate vitamin A status in livestock through dietary interventions and improved animal management practices can significantly benefit animal health and well-being. However, further research is still needed to optimize dosing strategies and fully understand the relationship between vitamin A and oxidative stress in different animal species and production systems. Therefore, continued research efforts are essential to fully harness the potential of vitamin A as an effective tool for mitigating oxidative stress and improving animal welfare. [ABSTRACT FROM AUTHOR]

Vitamin A, a critical micronutrient, plays a vital role in maintaining poultry health and maximizing productivity. This comprehensive review paper conducts a thorough analysis of the consequences of vitamin A deficiency in domestic fowl. It delves into the physiological functions of vitamin A and investigates how hypovitaminosis A impacts growth, immune function, reproduction, and overall poultry performance. Additionally, the review explores effective strategies for preventing and managing vitamin A deficiency, such as dietary adjustments and supplementation, while addressing the specific requirements for vitamin A intake. The implementation of these strategies holds immense importance in optimizing poultry management practices and achieving peak performance in poultry production. A profound understanding of the prevalence and factors contributing to clinical and subclinical vitamin A deficiency in domestic fowl is essential for ensuring the efficiency of poultry farming operations. Recognizing the pivotal role of vitamin A and applying the appropriate measures empowers poultry farmers to enhance the health outcomes and overall performance of their flocks. [ABSTRACT FROM AUTHOR]

The skin is the most-extensive and -abundant tissue in the human body. Like many organs, as we age, human skin experiences gradual atrophy in both the epidermis and dermis. This can be primarily attributed to the diminishing population of epidermal stem cells and the reduction in collagen, which is the primary structural protein in the human body. The alterations occurring in the epidermis and dermis due to the aging process result in disruptions to the structure and functionality of the skin. This creates a microenvironment conducive to age-related skin conditions such as a compromised skin barrier, slowed wound healing, and the onset of skin cancer. This review emphasizes the recent molecular discoveries related to skin aging and evaluates preventive approaches, such as the use of topical retinoids. Topical retinoids have demonstrated promise in enhancing skin texture, diminishing fine lines, and augmenting the thickness of both the epidermal and dermal layers. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of this study is three-fold. Firstly, to evaluate an enhanced vitamin C serum (eVCS) and its' combination with a retinolbakuchiol serum (RBS) on pigmentation in vitro. Secondly, to evaluate the effect of the eVCS on skin function ex vivo. Lastly, to evaluate eVCS and RSB in the treatment of facial hyperpigmentation and overall photodamage across a range of opposing environments. METHODS: MelanoDerm™ tissues were topically treated with the eVCS, and a eVCS and RSB blend for 14 days, and then a melanin assay was performed. Surgical waste facial skin explants were incubated with the eVCS or control for five days and then fixed and stained for skin physiology and structure. A 12-week, IRB approved, study on female subjects (n=29, aged 35 to 65) with moderate global facial hyperpigmentation and overall photodamage was completed. Clinical assessment, tolerability measurements, and subject-assessments were performed baseline at Weeks 6, 8, and 12. Investigator Global Aesthetic Improvement Score was completed at Week 12. RESULTS: The eVCS-treated facial skin explants achieved a significant 145 percent collagen increase compared to control. The eVCS-RSB combination proved synergistic in reducing melanin compared to the eVCS alone. The eVCSRSB combination demonstrated significant clinical improvement at all timepoints and was well tolerated. Subject responses were favorable and GAIS score of 3.0 was achieved at Week 12, indicating an improvement. LIMITATIONS: Limitations include lack of placebo or vehicle control. CONCLUSION: The product pairing, eVCS and RSB, offers patients an efficacious and well-tolerated treatment to target pigmentation and photodamage. [ABSTRACT FROM AUTHOR]

Objective: Retinol (Vitamin A) is one of the most effective molecules for the treatment of skin aging. However, it degrades rapidly under the influence of light, oxygen, metal ions, and oxidizing agents. To prevent this, stabilizing systems are used commonly. Notably, butylated hydroxytoluene (2,6‐di‐tert‐butyl‐p‐cresol) (BHT) and ethylenediaminetetraacetic acid (EDTA) salts exhibit excellent antioxidant and metal‐chelating properties but are not eco‐friendly. In this study, our goal was to develop a new eco‐friendly stabilization system for retinol‐based formulations such that the system does not interfere with retinol skin absorption, nor its clinical efficacy. Methods: An evaluation tool called the Sustainable Product Optimization Tool (SPOT) was used to assess the environmental performance of formulations containing retinol and the various stabilizers investigated. Accelerated stability tests were performed on formulations stored for 2 months at 4 and 45°C (ISO/TR Standard 18811 2018 directives). Long‐term stability evaluation was done on formulations stored for 24‐months at room temperature. Retinol skin absorption was assessed by the Franz cell method using human skin explants (OECD guideline 428). Finally, a clinical study was performed to evaluate the cosmetic performance of a 0.3% stabilized retinol formulation. Results: N,N'‐ethylenediamine disuccinic acid ([S,S]‐EDDS isomer) and pentaerythritol tetrakis(3,5‐di‐tert‐butyl‐4‐hydroxyhydrocinnamate) (PBHC) showed higher biodegradability and a reduced water footprint compared with those of BHT and EDTA. The SPOT simulation gave [S,S]‐EDDS + PBHC a score of 10 versus 8.84 for EDTA + BHT. Moreover, [S,S]‐EDDS + PBHC better controlled the chemical degradation of retinol compared with EDTA + BHT. Retinol skin absorption was also achieved in the case of a formulation containing [S,S]‐EDDS + PBHC, and several skin attributes improved significantly after 12 weeks of product use, with over 75% of the panel perceiving benefits. Conclusion: Regarding retinol stabilization, the PBHC + [S,S]‐EDDS combination is an eco‐friendlier and more effective alternative to BHT + EDTA. [ABSTRACT FROM AUTHOR]

Simple Summary: In the intensive farming process of laying ducks, the intestinal tract is susceptible to oxidative stress, which results in the impairment of intestinal barrier function. This study investigated the effects of retinol and its transformation product, retinoic acid, on duck intestinal cells under oxidative stress. Cells were treated with different ratios of retinol and retinoic acid, and their viability, antioxidant capacity, and barrier function were assessed. The expression of genes related to oxidative stress and barrier function was measured. The results showed that treatment with different ratios of retinol and retinoic acid improved cell viability, antioxidant capacity, and barrier function. High retinoic acid treatment enhanced cell activity and barrier function by affecting certain pathways, while high retinol treatment promoted barrier repair through different pathways. This study highlights the roles of retinol and retinoic acid in protecting duck intestinal epithelial cells from oxidative stress and enhancing barrier function and provides insights into their underlying mechanisms. This understanding could contribute to developing strategies to mitigate oxidative damage and improve intestinal health. This study aimed to investigate the effects and mechanisms of retinol and retinoic acid on primary duck intestinal epithelial cells under oxidative stress induced by H2O2. Different ratios of retinol and retinoic acid were used for treatment. The study evaluated the cell morphology, viability, antioxidative capacity, and barrier function of cells. The expression of genes related to oxidative stress and the intestinal barrier was analyzed. The main findings demonstrated that the treated duck intestinal epithelial cells exhibited increased viability, increased antioxidative capacity, and improved intestinal barrier function compared to the control group. High retinoic acid treatment improved viability and gene expression, while high retinol increased antioxidative indicators and promoted intestinal barrier repair. Transcriptome analysis revealed the effects of treatments on cytokine interactions, retinol metabolism, PPAR signaling, and cell adhesion. In conclusion, this study highlights the potential of retinol and retinoic acid in protecting and improving intestinal cell health under oxidative stress, providing valuable insights for future research. [ABSTRACT FROM AUTHOR]

Background: Neck skin is thinner and has a more delicate dermal layer than facial skin. The studied product was specifically formulated for the neck combining a hydrating delivery system with a trifunctional corrective technology composed of 0.2% pure retinol, 2.5% tripeptide concentrate, and 5.0% glaucine complex to help improvement in signs of aging. Objectives: To evaluate cosmetic and histologic changes 3 months after treatment using immunostains for Type I collagen, Type III collagen, and glycosaminoglycan (GAGS). In addition, overall clinical improvement in photoaged skin was measured by both Griffith's photonumeric photoaging scale, photographic improvement, and questionnaires. Methods: This study was an open‐label, blinded clinical trial evaluating a combined retinol, tripeptide, and glaucine containing cream in the treatment of photo‐aged skin. The study enrolled a total of 20 healthy male or female subjects, who applied the product for 3 months to their face and neck. Results: Clinical as well histologic changes were consistent with improvement in all 20 subjects. Conclusion: Use of a combined retinol, tripeptide, and glaucine containing cream led to both clinical and histologic improvement of phototoaging. [ABSTRACT FROM AUTHOR]

Background: The neck region is an area that can be indicative of signs of skin aging. A novel topical product that combines multiple active ingredients including retinol, tripeptide and glaucine was formulated to specifically target neck aging correction and complement post‐procedure as part of an integrated skincare regimen. Objectives: To evaluate the efficacy of a topical neck treatment through clinical subject evaluation, in addition to ultrasound and biopsy assessment. Methods: Evaluation for the efficacy of this novel topical product on improving the aging signs of neck skin was performed in multiple clinical trials. The first trial focused on clinical efficacy and included clinical assessment, subject questionnaires, ultrasound imaging and digital photographs. The second trial focused on biomarker analysis through skin biopsy. Results: Data from the clinical trials showed that aging signs on the neck were significantly improved after 12 or 16 weeks of product usage. Changes were readily observed by clinical evaluators and participants. They were documented with digital photos, ultrasound images, and biomarker expression in the skin which clearly display the improvements. Conclusions: This novel topical product is effective in treating the aging signs on the neck skin and has been shown to provide statistically significant improvement on a myriad of neck aging attributes including fine lines/wrinkles, crepiness, laxity, and texture. [ABSTRACT FROM AUTHOR]

The main purpose of this systematic review was to evaluate the association between the stroke (risk of stroke and the mortality due to stroke) and vitamin A, its organic compounds and its provitamins. Major databases including PubMed, Scopus, and Web of Science were searched. Studies with human samples were included for risk assessment. The association was assessed using odds ratio (log(OR)) and a random-effect model. I2 statistic, variance (tau2) and prediction interval were used for heterogeneity assessment. The funnel plot was used for publication bias. Twenty-one studies including 5789 stroke patients were retrieved. Twenty studies had sufficient information for quantitative analyses. The pooled effect showed an inverse association between vitamin A and its organic compound with the risk of stroke (log(OR) = −0.46 95%CI (−0.81;−0.12)) and with the risk of mortality due to stroke (log(OR) = −0.39 95%CI (−0.74;−0.04)). However, according to subgroup analyses, the association was dependent on the compound in a way that retinol and beta-carotene were the most effective compounds. The effects of several confounding factors and the threshold levels for vitamin A and its organic compound on the effectiveness were discussed. Insufficiency of retinol and beta-carotene significantly increased the risk of stroke; however, due to heterogeneity between studies more studies are needed for evaluating clinical significance of this outcome. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) may be associated with ABCA4 variants and is characterized by the accumulation of visual cycle-byproduct lipofuscin. Reducing retinol-binding protein 4 (RBP4), a retinol transporter protein, may reduce lipofuscin production. This study aims to assess the associations between plasma RBP4, the ABCA4 variation, and AMD severity. Sixty-seven participants were grouped into healthy/mild AMD (n = 32) and severe AMD (n = 35) groups. The latter group was older than the former group and had higher levels of RBP4 (36.8 ± 8.3 vs. 30.4 ± 7.0 μg/mL, p = 0.0012). The ten participants with six ABCA4 linked-variants had higher RBP4 than those without (37.8 ± 7.7 vs. 32.4 ± 7.9 μg/mL; p = 0.026), and eight of them had severe AMD. Univariate analyses showed that severe AMD was related to older age (OR, 1.26; 95% CI, 1.13–1.40; p < 0.0001) and to higher RBP4 levels (OR, 1.12; 95% CI, 1.04–1.20; p = 0.003), whereas the linked ABCA4 variants had no associations. After adjustment, however, only age remained significantly associated with severe AMD. This pilot study shows a trend of higher plasma RBP4 levels in severe AMD or the ABCA4-linked variants, and further age-matched studies are warranted. [ABSTRACT FROM AUTHOR]

Vitamin A is a fat-soluble micronutrient vital for the immune system, cellular differentiation, epithelial barrier function, and eyesight; they also play a significant function as a potent antioxidant regulating oxidative stress and the onset of cancer. There are two ways to get it through food: Provitamin A (beta-carotenoid) and preformed Vitamin A (retinol and retinyl ester). Uncontrolled cell proliferation and the development of metastatic features are characteristics of cancer initiated by agents such as aflatoxin, tobacco smoke's carcinogenic compounds, and solar ultraviolet radiation. Vitamin A, an antioxidant vitamin, is hypothesized to exert chemo-preventive effects and reduce the risk of cancer by preventing tissue damage through the capture of organic free radicals, an end-product of numerous metabolic processes. This review is performed to investigate the association between Vitamin A and cancer. From March 2017 to March 2022, relevant articles were searched through PubMed, Science Direct, and Google Scholar databases. All the studies involving Vitamin A and cancer were included in this review. Intake of Vitamin A was significantly inversely associated with improved cancer prognosis. The present review demonstrates that there is an inverse association between Vitamin A and cancer treatment. [ABSTRACT FROM AUTHOR]

Nowadays, there exists a huge interest in producing innovative, high-performance, biofunctional, and cost-efficient electrospun biomaterials based on the association of biocompatible polymers with bioactive molecules. Such materials are well-known to be promising candidates for three-dimensional biomimetic systems for wound healing applications because they can mimic the native skin microenvironment; however, many open questions such as the interaction mechanism between the skin and the wound dressing material remain unclear. Recently, several biomolecules were intended for use in combination with poly(vinyl alcohol) (PVA) fiber mats to improve their biological response; nevertheless, retinol, an important biomolecule, has not been combined yet with PVA to produce tailored and biofunctional fiber mats. Based on the abovementioned concept, the present work reported the fabrication of retinol-loaded PVA electrospun fiber mats (RPFM) with a variable content of retinol (0 ≤ Ret ≤ 25 wt.%), and their physical–chemical and biological characterization. SEM results showed that fiber mats exhibited diameters distribution ranging from 150 to 225 nm and their mechanical properties were affected with the increasing of retinol concentrations. In addition, fiber mats were able to release up to 87% of the retinol depending on both the time and the initial content of retinol. The cell culture results using primary mesenchymal stem cell cultures proved the biocompatibility of RPFM as confirmed by their effects on cytotoxicity (low level) and proliferation (high rate) in a dose-dependent manner. Moreover, the wound healing assay suggested that the optimal RPFM with retinol content of 6.25 wt.% (RPFM-1) enhanced the cell migratory activity without altering its morphology. Accordingly, it is demonstrated that the fabricated RPFM with retinol content below the threshold 0 ≤ Ret ≤ 6.25 wt.% would be an appropriate system for skin regenerative application. [ABSTRACT FROM AUTHOR]

The rat hepatic stellate cell line PAV-1 was established two decades ago and proposed as a cellular model to study aspects of hepatic retinoic acid metabolism. This cell line exhibits a myofibroblast-like phenotype but also has the ability to store retinyl esters and synthesize retinoic acid from its precursor retinol. Importantly, when cultured with palmitic acid alone or in combination with retinol, the cells switch to a deactivated phenotype in which the proliferation and expression of profibrogenic marker genes are suppressed. Despite these interesting characteristics, the cell line has somehow fallen into oblivion. However, based on the fact that working with in vivo models is becoming increasingly complicated, genetically characterized established cell lines that mimic aspects of hepatic stellate cell biology are of fundamental value for biomedical research. To genetically characterize PAV-1 cells, we performed karyotype analysis using conventional chromosome analysis and multicolor spectral karyotyping (SKY), which allowed us to identify numerical and specific chromosomal alteration in PAV-1 cells. In addition, we used a panel of 31 species-specific allelic variant sites to define a unique short tandem repeat (STR) profile for this cell line and performed bulk mRNA-sequencing, showing that PAV-1 cells express an abundance of genes specific for the proposed myofibroblastic phenotype. Finally, we used Rhodamine-Phalloidin staining and electron microscopy analysis, which showed that PAV-1 cells contain a robust intracellular network of filamentous actin and process typical ultrastructural features of hepatic stellate cells. [ABSTRACT FROM AUTHOR]

Chronic wounds and their treatment present a significant burden to patients and healthcare systems alike, with their management further complicated by bacterial infection. Historically, antibiotics have been deployed to prevent and treat infections, but the emergence of bacterial antimicrobial resistance and the frequent development of biofilms within the wound area necessitates the identification of novel treatment strategies for use within infected chronic wounds. Here, several non-antibiotic compounds, polyhexamethylene biguanide (PHMB), curcumin, retinol, polysorbate 40, ethanol, and D-α-tocopheryl polyethylene glycol succinate 1000 (TPGS) were screened for their antibacterial and antibiofilm capabilities. The minimum inhibitory concentration (MIC) and crystal violet (CV) biofilm clearance against two bacteria frequently associated with infected chronic wounds, Staphylococcus aureus and Pseudomonas aeruginosa, were determined. PHMB was observed to have highly effective antibacterial activity against both bacteria, but its ability to disperse biofilms at MIC levels was variable. Meanwhile, TPGS had limited inhibitory activity but demonstrated potent antibiofilm properties. The subsequent combination of these two compounds in a formulation resulted in a synergistic enhancement of their capability to kill both S. aureus and P. aeruginosa and disperse their biofilms. Collectively, this work highlights the utility of combinatory approaches to the treatment of infected chronic wounds where bacterial colonization and biofilm formation remains significant issues. [ABSTRACT FROM AUTHOR]

The current study aimed to characterize cellular uptake and bioconversion of retinol in fully differentiated human immortalized keratinocytes cells (HaCaT) and artificial skin by measuring the cell integrity of skin barriers, time‐dependent transport of retinol, and bioconversion to its metabolites. The expression of epidermal differentiation related genes including Keratin 1 (KRT1), Keratin 10 (KRT10), and Involucrin (IVL) significantly increased in differentiated HaCaT. TEER of HaCaT did not decrease after incubating retinol compared to control (p > 0.05), indicating that retinol tends to maintain strength and integrity of epidermal barrier. TEER of artificial skin decreased treatment of retinol for 2 h, but it was recovered after 4 h. During retinol transport, metabolite was eluted at 13.37 and 13.82 min of basal medium of both keratinocytes and artificial skin, which was identified as retinoic acid by product ion of m/z 283.47. Retinol appeared to be accumulated in keratinocytes, but its uptake tends to be reduced in a time‐dependent manner. Retinoic acid converted from retinol in keratinocytes was time dependently transported. In case of artificial skin, retinol was mostly found in apical at initial incubation time, but it was reduced during incubation for 24 h. Retinoic acid was time‐dependently found in a basal, which was converted via epidermis–dermis. Results from the current study suggest that topical application of retinol to human skin optimal concentration and time exposure could maintain epidermal barrier function and promote skin function due to its remarkable bioconversion to retinoic acid in the epidermis–dermis. [ABSTRACT FROM AUTHOR]

• Vitamin A and E are stable at RT for up to 24 hrs, +4°C for up to 7 days, and −20 °C for up to 22 days. • Decreased vitamin A and E sample stability was not concentration dependent. • Vitamin A and E samples were more stable in amber Eppendorf tubes at RT, relative to when stored in clear Eppendorf tubes. Vitamin A and Vitamin E, a group of lipid-soluble vitamins, can be degraded by photolysis and photooxidation after exposure to light. As an essential area of the preanalytical stage, inappropriate storage conditions of patient samples could lead to inaccurate results. In this study, we evaluated three of the most common preanalytical storage conditions (RT, +4°C, and −20 °C) in the workflow in the clinical laboratory setting using both clear and amber Eppendorf tubes. Analyte stability in each storage condition was tested with five patient pools. After 24 hrs at RT, a significant decrease in vitamin A and E was observed for samples stored in clear Eppendorf tubes (19.2 % and 17.9 %, for vitamin A and E, respectively), compared with samples stored in amber Eppendorf tubes (9.1 % and 7.3 %), respectively. After the specimen was stored at 4 °C for 7 days, vitamin A concentrations decreased in clear tubes by 14.7 % and in amber tubes by 12.7 %. Similarly, vitamin E concentrations decreased in both clear and amber tubes by 11.2 % and 13.4 %, respectively. Both vitamin A and vitamin E demonstrated acceptable stability in clear and amber Eppendorf tubes at −20 °C for up to 22 days. It is preferable to use amber tubes to protect vitamin A and E from light during short term storage. Storage of vitamin A and E specimens beyond 7 days should be at −20 °C. [ABSTRACT FROM AUTHOR]

Retinol, the main active form of vitamin A, plays a role in maintaining vision, immune function, growth, and development. It also inhibits tumor growth and alleviates anemia. Here, we developed a Saccharomyces cerevisiae strain capable of high retinol production. Firstly, the de novo synthesis pathway of retinol was constructed in S. cerevisiae to realize the production of retinol. Second, through modular optimization of the metabolic network of retinol, the retinol titer was increased from 3.6 to 153.6 mg/L. Then, we used transporter engineering to regulate and promote the accumulation of the intracellular precursor retinal to improve retinol production. Subsequently, we screened and semi-rationally designed the key enzyme retinol dehydrogenase to further increase the retinol titer to 387.4 mg/L. Lastly, we performed two-phase extraction fermentation using olive oil to obtain a final shaking flask retinol titer of 1.2 g/L, the highest titer reported at the shake flask level. This study laid the foundation for the industrial production of retinol. [ABSTRACT FROM AUTHOR]

Phenotypic plasticity and resistance to climatic conditions allowed the wild boar Sus scrofa L. to expand its historical range and move away its Northern border. For the adaptation to living at the periphery of its range under severe conditions of the North, the status of vitamins A and E, which are natural antioxidants critical for growth, reproduction and immunity maintenance, is of vital importance. The aim of this work was to investigate the content of retinol, α-tocopherol, and the low-molecular-weight antioxidant glutathione (GSH) in the liver, kidney, heart, skeletal muscle, lungs, and spleen of the wild boars (n = 65) aged 0.5–8 years, living in the Northwest of Russia. Our results indicate that the studied animals practically did not differ in the retinol content from their counterparts living in the Central and Southern Europe, but had lower tissue α-tocopherol levels, which is probably due to the limited food resources and harsh climatic conditions of the cold season in the North. Vitamin and GSH levels in most tissues were comparable in piglets and adult animals. With age, retinol and α-tocopherol accumulated in the liver and kidney, while α-tocopherol alone accumulated in the heart, which is typical for other mammalian species. An increase in the GSH level was found in the lungs of animals over 5 years of age. The revealed vitamin status, which was formed in the wild boar under conditions of the Russia's Northwest, as well as the peculiarities of the age-related dynamics of the above indices, may serve a compelling evidence for the successful adaptation of this species to inhabiting the northern periphery of its range, as confirmed by the growth of its population. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) is a developmental disorder that results in incomplete diaphragm formation, pulmonary hypoplasia, and pulmonary hypertension. Although a variety of genes have been linked to its etiology, CDH is not a monogenetic disease, and the cause of the condition is still unclear in the vast majority of clinical cases. By comparing human clinical data and experimental rodent data from the literature, we present clear support demonstrating the importance of vitamin A (vitA) during the early window of pregnancy when the diaphragm and lung are forming. Alteration of vitA signaling via dietary and genetic perturbations can create diaphragmatic defects. Unfortunately, vitA deficiency is chronic among people of child-bearing age, and this early window of diaphragm development occurs before many might be aware of pregnancy. Furthermore, there is an increased demand for vitA during this critical period, which exacerbates the likelihood of deficiency. It would be beneficial for the field to further investigate the connections between maternal vitA and CDH incidence, with the goal of determining vitA status as a CDH risk factor. Regular clinical monitoring of vitA levels in child-bearing years is a tractable method by which CDH outcomes could be prevented or improved. [ABSTRACT FROM AUTHOR]

Purpose: 1) To test the hypothesis of the existence of a perinatal vitamin A (VA) programming of VA metabolism and to better understand the intestinal regulation of VA metabolism. Methods: Offspring from rats reared on a control (C) or a VA-deficient (D) diet from 6 weeks before mating until offspring weaning, i.e., 7 weeks after mating, were themselves reared on a C or D diet for 19 weeks, resulting in the following groups: C–C (parents fed C—offspring fed C), D-C, C-D and D-D. VA concentrations were measured in plasma and liver. β-Carotene bioavailability and its intestinal conversion rate to VA, as well as vitamin D and E bioavailability, were assessed after gavages with these vitamins. Expression of genes involved in VA metabolism and transport was measured in intestine and liver. Results: C–D and D–D had no detectable retinyl esters in their liver. Retinolemia, hepatic retinol concentrations and postprandial plasma retinol response to β-carotene gavage were higher in D–C than in C–C. Intestinal expression of Isx was abolished in C–D and D–D and this was concomitant with a higher expression of Bco1, Scarb1, Cd36 and Lrat in males receiving a D diet as compared to those receiving a C diet. β-Carotene, vitamin D and E bio-availabilities were lower in offspring receiving a D diet as compared to those receiving a C diet. Conclusion: A VA-deficient diet during the perinatal period modifies the metabolism of this vitamin in the offspring. Isx-mediated regulation of Bco1 and Scarb1 expression exists only in males severely deficient in this vitamin. Severe VA deficiency impairs β-carotene and vitamin D and E bioavailability. [ABSTRACT FROM AUTHOR]

Background: Vitamin A deficiency (VAD) is common in populations with limited dietary diversity and access to vitamin A-rich foods. Objectives: This analysis aimed to determine the impact of supplementing children's diets with 1 egg/d on the concentration of plasma retinol and RBP and the prevalence of VAD. Methods: Children age 6-9 mo living in the Mangochi district of Malawi were individually randomly assigned to receive 1 egg/d for 6 mo (n = 331) or continue their usual diet (n = 329) in the Mazira trial (clinicaltrials.gov; NCT03385252). This secondary analysis measured plasma retinol by HPLC and RBP, CRP, and α-1-acid glycoprotein (AGP) by ELISA techniques at enrollment and 6 mo follow-up. Retinol and RBP were adjusted for inflammation, and mean concentrations were compared between groups using linear regression models. In addition, prevalence ratios of VAD (retinol <0.7 μmol/L) were compared between groups using log-binomial or modified Poisson regression models. Results: After 6 mo of study participation, 489 were assessed for retinol (egg: n = 238; control: n = 251), and 575 (egg: n = 281; control: n = 294) were assessed for RBP. Prevalence of inflammation (CRP >5 mg/L or AGP >1 g/L: 62%) and inflammation-adjusted VAD (7%) at enrollment did not differ between groups. At follow-up, the egg intervention group did not differ from the control in inflammation-adjusted retinol [geometric mean (95% CI); egg: 1.10 μmol/L (1.07, 1.13); control: 1.08 (1.05, 1.12)], RBP [egg: 0.99 μmol/L (0.96, 1.02); control: 0.97 (0.94, 1.00)], or prevalence of VAD [egg: 6%; control: 3%; prevalence ratio: 1.87 (0.83, 4.24)]. Conclusions: Provision of 1 egg/d did not impact VAD, plasma retinol, or RBP among young children in rural Malawi, where the prevalence of VAD was low. Curr Dev Nutr 2023;x:xx. [ABSTRACT FROM AUTHOR]

Context: The mutations in the TP53 gene are the most frequent (50–60% of human cancer) genetic alterations in cancer cells, indicating the critical role of wild-type p53 in the regulation of cell proliferation and apoptosis upon oncogenic stress. Most missense mutations are clustered in the DNA-binding core domain, disrupting DNA binding ability. However, some mutations like Y220C occur outside the DNA binding domain and are associated with p53 structure destabilization. Overall, the results of these mutations are single amino acid substitutions in p53 and the production of dysfunctional p53 protein in large amounts, consequently allowing the escape of apoptosis and rapid progression of tumor growth. Thus, therapeutic targeting of mutant p53 in tumors to restore its wild-type tumor suppression activity has immense potential for translational cancer research. Various molecules have been discovered with modern scientific techniques to reactivate mutant p53 by reverting structural changes and/or DNA binding ability. These compounds include small molecules, various peptides, and phytochemicals. TP53 protein is long thought of as a potential target; however, its translation for therapeutic purposes is still in its infancy. The study comprehensively analyzed the therapeutic potential of small phytochemicals from Foeniculum vulgare (Fennel) with drug-likeness and capability to reactivate mutant p53 (Y220C) through molecular docking simulation. The docking study and the stable molecular dynamic simulations revealed juglalin (− 8.6 kcal/mol), retinol (− 9.14 kcal/mol), and 3-nitrofluoranthene (− 8.43 kcal/mol) significantly bind to the mutated site suggesting the possibility of drug designing against the Y220C mutp53. The study supports these compounds for further animal based in vivo and in vitro research to validate their efficacy. Methods: For the purposes of drug repurposing, recently in-silico methods have presented with opportunity to rule out many compounds which have less probability to act as a drug based on their structural moiety and interaction with the target macromolecule. The study here utilizes molecular docking via Autodock 4.2.6 and molecular dynamics using Schrodinger 2021 to find potential therapeutic options which are capable to reactive the mutated TP53 protein. [ABSTRACT FROM AUTHOR]

Vitamin A is an essential nutrient, for both production and reproduction of farm animals, however, most animals are unable to synthesize de novo precursors of vitamin A (β-carotene), and dietary supplementation is mandatory. The current paper aims to evaluate the analytical parameters and to improve the method efficiency for determining β-carotene content in red yeast and the internal laboratory validation protocol. Our method stands for the ultravioletvisible spectrophotometric uses, having the Lambert-Beer law as the basis. To determine the β-carotene content, dimethyl-sulfoxide was employed as a solvent, calibration curve, and visible spectra were evaluated (300-900 nm). The linearity of beta carotene measured at 465 nm using the UV-Vis method linearity range was 6.1-36.6 μg/ml, R2=0.997, LOD = 5.39 μg/ml, LOQ = 16.32 μg/ml, SD less than 5% and RSD in between 1-15%. In conclusion, the β-carotene spectroscopic method determination is a cheap, and efficient method, suitable for β-carotene determination and retinol and retinoic acid estimation for nonconventional feed additives such as yeasts. [ABSTRACT FROM AUTHOR]

Cellular Retinoic Acid Binding Protein-1 (CRABP1) facilitates retinoid metabolism; however, an abnormal expression might influence cancers developed. Biopsy samples were evaluated from patients with cervical cancer (CC), high-grade (HSIL), and lowgrade squamous intraepithelial lesions (LSIL) (n= 66) Clinic/pathological information was obtained from patients. CRABP1 gene expression was examined by RT-PCR and CRABP1 protein by immunohistochemistry (IHC) techniques. The expression of the CRABP1 gene is shown to be significantly lower in the HSIL group (p= 0.008). CRABP1 protein was expressed in 90.3% of tissues, and only in CC was presented absence of protein (9.7%). Overweight/obesity might increase the gene (p= 0.019) but not the protein expression (p= 0.053). Also, a gene expression increase was shown in high serum retinol concentration (p= 0.047) and the presence of HVP-16 (p= 0.011) (gene expression but not the protein, p > 0.05). Menopause patients were associated with an absent/weak CRABP1 immunostaining (p= 0.008). Finally, CRABP1 and associated factors might be used as biomarkers to track the progression and persistence of cervical cancer on tissue. [ABSTRACT FROM AUTHOR]

Vitamin A refers to a group of fat-soluble compounds with retinol activity, including all-trans retinol and pro-vitamin A carotenoids. Bioactive compounds include retinal and all-trans retinoic acid with important functions in vision, immune function, growth, and development. The literature search that was performed for the current scoping review yielded a total of seven publications relevant to setting the recommended daily intake for vitamin A. In total, six publications assessed the relationship of serum retinol and/or dietary vitamin A intake with fracture risk (n = 2), cancer (n = 3), and deficiency after bariatric surgery (n = 1). One additional report by the European Food Safety Administration (EFSA) with updated average requirements was included. The outcomes-based systematic reviews and meta-analyses showed positive associations for vitamin A intake and serum retinol with risk of hip fracture. Weak or inconclusive associations were observed for cancer or obesity. One publication by EFSA with updated estimated average requirements and population reference intakes for dietary vitamin A intakes was published in 2015. The EFSA recommendations and estimated average requirements are based on a European reference population, with body weights derived from an assumed body mass index of 22, which might be too low and not representative of the Nordic and Baltic populations, and consequently resulting in lower estimated average requirements and recommendations. In conclusion, there were limited new outcomes-based data for vitamin A and health outcomes. [ABSTRACT FROM AUTHOR]

Fat-soluble vitamins and fatty acids are very sensitive to high temperature and oxidation. In this study, stability of vitamins A and D, and physiochemical changes were investigated in two types of oils, palm olein (PO) and a blend of PO and sunflower oil (OB). The intermittent frying was performed at two different temperatures 160 and 190 °C. Batches of French fries (500 g) were fried in a deep-fat fryer for 5 cycles, a cycle per day. In each cycle, food was fried every 15 min with a total frying time of 5 h per day. Oil samples were taken at the end of each heating cycle to measure vitamins A and D concentration, free fatty acid (FFA), peroxide value (PV) and color. In PO, vitamin A was reduced by 96.7% after 25 h of frying at 160 °C and it was completely depleted after 15 h at 190 °C. In OB, the vitamin was reduced by 72.2% after 25 h of frying at 160 °C; and it was completely depleted at 190 °C at the end of frying cycles. Vitamin D was less stable, its content in PO decreased by 67.0% and 80.0% at 160 °C and 190 °C, respectively, after 5 h of frying. In OB, it was reduced by 50.0% and 67.0% at 160 °C and 190 °C, respectively, after 5 h of frying. It was found that both types of oil and frying temperatures showed significant effect on vitamin A concentration, while they did not show any effect on vitamin D. Red color increased linearly with frying time in both oils, while fried at two frying temperatures. The change in color was significantly associated with the vitamin A depletion. A low, but significant, association was found between color changes and depletion of vitamin D. In conclusion, the stability of these vitamins depended on the types of oil and temperature of frying. These were more stable in OB compared to PO, and similar stability was observed in the cases of FFA and PV. [ABSTRACT FROM AUTHOR]

Polyvinyl alcohol (PVA) hydrogels are well-known biomimetic 3D systems for mammalian cell cultures to mimic native tissues. Recently, several biomolecules were intended for use in PVA hydrogels to improve their biological properties. However, retinol, an important biomolecule, has not been combined with a PVA hydrogel for culturing bone marrow mesenchymal stem (BMMS) cells. Thus, for the first time, the effect of retinol on the physicochemical, antimicrobial, and cell proliferative properties of a PVA hydrogel was investigated. The ability of protein (3.15 nm) and mineral adsorption (4.8 mg/mL) of a PVA hydrogel was improved by 0.5 wt.% retinol. The antimicrobial effect of hydrogel was more significant in S. aureus (39.3 mm) than in E. coli (14.6 mm), and the effect was improved by increasing the retinol concentration. The BMMS cell proliferation was more upregulated in retinol-loaded PVA hydrogel than in the control at 7 days. We demonstrate that the respective in vitro degradation rate of retinol-loaded PVA hydrogels (RPH) (75–78% degradation) may promote both antibacterial and cellular proliferation. Interestingly, the incorporation of retinol did not affect the cell-loading capacity of PVA hydrogel. Accordingly, the fabricated PVA retinol hydrogel proved its compatibility in a stem cell culture and could be a potential biomaterial for tissue regeneration. [ABSTRACT FROM AUTHOR]

The chemical composition, content of cholesterol, retinol and α-tocopherol, and the total antioxidant capacity of different tissues from wild beavers were investigated. The total phenolic contents and free radical scavenging activity (DPPH and ABTS assays) were analysed spectrophotometrically, and fat-soluble vitamins were quantified using high-performance liquid chromatography. The type of tissue (skeletal muscle from loin and hind leg vs. adipose tissue from subcutaneous fat and tail) significantly affected content of all chemical components. The concentration of cholesterol was not related to total fat content. The retinol and α-tocopherol contents (µg/100 g) were significantly higher in the tail (13.0 and 391.2) and subcutaneous fat (12.2 and 371.3) compared to skeletal muscles (as an average 9.1 and 361.4). Among all tissues the tail showed significantly the highest values of DPPH (3.07 mM TE/100 g), ABTS (3.33 mM TE/100 g), and total phenolics (TPC, 543.7 mg GAE/100 g). The concentration of retinol was positively correlated with α-tocopherol (0.748, p < 0.001), and both vitamins were very strongly correlated with DPPH (0.858 and 0.886, p < 0.001), ABTS (0.894 and 0.851, p < 0.001), and TPC (0.666 and 0.913, p < 0.001). The principal component analysis proved that moisture, ash, and protein contents were representative for skeletal muscles, whereas, retinol, α-tocopherol, ABTS and DPPH accurately described the antioxidant capacity of tissue from the tail. [ABSTRACT FROM AUTHOR]

Background Although previous studies have shown that vitamin A deficiency is associated with incident tuberculosis (TB) disease, the direction of the association has not been established. We investigated the impact of vitamin A deficiency on TB disease progression. Methods We conducted a longitudinal cohort study nested within a randomized clinical trial among HIV-infected patients in Haiti. We compared serial vitamin A levels in individuals who developed TB disease to controls matched on age, gender, follow-up time, and time to antiretroviral therapy initiation. We also evaluated histopathology, bacterial load, and immune outcomes in TB infection in a guinea pig model of dietary vitamin A deficiency. Results Among 773 participants, 96 developed incident TB during follow-up, 62.5% (60) of whom had stored serum samples obtained 90–365 days before TB diagnosis. In age- and sex- adjusted and multivariate analyses, respectively, incident TB cases were 3.99 times (95% confidence interval [CI], 2.41 to 6.60) and 3.59 times (95% CI, 2.05 to 6.29) more likely to have been vitamin A deficient than matched controls. Vitamin A–deficient guinea pigs manifested more extensive pulmonary pathology, atypical granuloma morphology, and increased bacterial growth after experimental TB infection. Reintroduction of dietary vitamin A to deficient guinea pigs after established TB disease successfully abrogated severe disease manifestations and altered cellular immune profiles. Conclusions Human and animal studies support the role of baseline vitamin A deficiency as a determinant of future TB disease progression. [ABSTRACT FROM AUTHOR]

Simple Summary: In many countries, the main source of venison is game shooting, but deer farming is growing intensively, partly as a consequence of greater interest in alternative meat species. The meat of cervids, including fallow deer, has a desirable, beneficial basic chemical composition, but there is little information on the concentrations of biologically active compounds (β-carotene, retinol and tocopherols). In the present study, we evaluated the contents of β-carotene, retinol and tocopherols, as well as the basic chemical compositions, of the meat and livers of fallow deer fed rations based on hay with different concentrated feeds (oat grain, protein concentrate and pellets). More retinol was contained in the livers and meat of fallow deer fed rations with protein concentrate or pellets (experimental groups) than in the livers and meat of fallow deer fed rations with oat grain (the control group). The proportions of the different concentrated feeds did not affect the basic chemical compositions and tocopherol contents in the fallow deer meat and livers. Based on our results, it was concluded that protein concentrate and pellets can be valuable components in the rations of farmed fallow deer. This study analyzed the chemical composition and contents of β-carotene, tocopherols and retinol in the longissimus dorsi (LD) muscles and livers of fallow deer (Dama dama L.) fed diets based on hay containing different concentrates (hay and oats—HO; hay, oats and protein concentrate—HOP; hay and pellets—HP). The provitamin and lipophilic vitamin contents in the samples of feed and animal tissues were determined by high-performance liquid chromatography (HPLC). The contents of retinol were nearly two-fold higher (p < 0.002) in the livers and many-fold higher in the LD muscles of fallow deer fed the HOP and HP diets. β-carotene was not identified in the livers or LD muscles of fallow deer. The concentrations of α-tocopherol and total tocopherols were higher in the livers and LD muscles of the animals that received the HO and HP diets, but the noted differences were not significant. The inclusion of various concentrates in the feed rations had no influence on the proximate chemical compositions of the livers or LD muscles of fallow deer. [ABSTRACT FROM AUTHOR]

Background: Bakuchiol (BAK), a meroterpene phenol abundant in the plant Psoralea corylifolia, is an emerging cosmeceutical agent with promising anti‐aging, anti‐inflammatory, and antibacterial properties. The trend for "clean" skincare products and search for anti‐aging retinoid alternatives have poised BAK as a "must‐have" ingredient in skincare. Aims: Our aim was to review the data for the applications of BAK in dermatology. Methods: This is a systematic review of PubMed. Results: Thirty articles matched our search terms ["Bakuchiol" and "Dermatology"] or ["Bakuchiol" and "Skin"] of which one did not meet inclusion criteria, 16 were pre‐clinical studies, seven clinical studies, three commentaries, two narrative reviews, and one report on adverse events. BAK has been mostly studied for its effects on photoaging, acne, and post‐inflammatory hyperpigmentation (PIH), showing beneficial results comparable to those achieved by topical retinoids. While having no structural resemblance to retinoids, BAK can function as a retinol analog, through retinol‐like regulation of gene expression. In in vivo studies, BAK was used alone or in combination with other products resulting in a significant reduction in photodamage, hyperpigmentation, wrinkle scores, and acne severity. Additionally, in vitro studies hinted at its anti‐cancer properties by inhibiting epidermal growth factor induced neoplastic cell transformation. Also, demonstrated potential applications in psoriasis by normalizing keratinocyte activity and in pigmentary disorders through inhibition of melanogenesis. There was one adverse event case reported of contact dermatitis in the literature. Conclusions: Bakuchiol is a retinol alternative with anti‐aging, antibacterial, and anti‐inflammatory properties. Additional studies are warranted to better understand its applications in dermatology. [ABSTRACT FROM AUTHOR]

Retinol concentrations in serum are significantly higher in patients on hemodialysis (HD) compared to healthy controls. Its lower concentrations have been reported to be an independent predictor of mortality. ATRA – all-trans retinoic acid – is an important compound related to retinol. The objective was to determine ATRA concentrations in serum and to find their association with the prognosis of patients on long-term HD. ATRA was determined by high-performance liquid chromatography in a group of 247 HD patients (follow-up five years) and 54 healthy controls. Although serum retinol concentrations were higher in the studied cohort of HD patients, ATRA was lower – median 1.13 (interquartile range 0.90–1.60) ng/mL in HD patients versus 1.42 (1.08–1.63) ng/mL in healthy controls, p = 0.02. Lower ATRA was significantly related to overall mortality of HD patients (HR (95%CI) 0.63 (0.47–0.85) per interquartile range, p = 0.003). The best prognosis was observed in patients with concentrations of both ATRA and retinol above the median (p = 0.003). We detected decreased retinoic acid levels in HD patients compared to healthy controls. Lower concentrations of ATRA represent a significant predictor of mortality and provide additional information to retinol. [ABSTRACT FROM AUTHOR]

Vitamin A (retinol) is a critical micronutrient required for the control of stem cell functions, cell differentiation, and cell metabolism in many different cell types, both during embryogenesis and in the adult organism. However, we must obtain vitamin A from food sources. Thus, the uptake and metabolism of vitamin A by intestinal epithelial cells, the storage of vitamin A in the liver, and the metabolis m of vitamin A in target cells to more biologically active metabolites, such as retinoic acid (RA) and 4-oxo-RA, must be precisely regulated. Here, I will discuss the enzymes that metabolize vitamin A to RA and the cytochrome P450 Cyp26 family of enzymes that further ox idize RA. Because much progress has been made in understanding the regulation of ALDH1a2 (RALDH2) actions in the intestine, one focus of this review is on the me tabolism of vitamin A in intestinal epithelial cells and dendritic cells. Another focus is on recent data that 4-oxo-RA is a ligand required for the maintenance of hematopoietic stem cell dormancy and the important role of RARβ (RARB) in these stem cells. Despite this progress, many questions remain in this research area, which links vitamin A metabolism to nutrition, immune functions, developmental biology, and nuclear receptor pharmacology. [ABSTRACT FROM AUTHOR]

Simple Summary: Fish-eating animals in human care receive whole fish that were frozen, stored and thawed before feeding. Nutrient losses have been documented, but exact changes are unknown. The aims of this study were to evaluate whether or not frozen fish lose vitamins and trace minerals during storage, and if different thawing methods have an influence on the degree of these losses. Whole herring, mackerel, and capelin were analyzed at four time points within a storage period of six months at −20 °C. Each time, three thawing methods were tested: refrigerator, room temperature and running water. The following nutrients were analyzed: vitamin A, B1, D3 and E, iron, copper, zinc, and selenium. Copper was below detection limits in all samples, vitamin B1 in most herring (44/48) and capelin samples (25/36), and vitamin D3 in half of the capelin samples (18/36). Significant decreases of vitamin A, D3 and E concentrations were observed during a storage period of six months. Thawing fish with different methods resulted in a significant change of concentration of vitamin A. It is essential to supplement vitamin B1 and E in diets containing whole fish, and it should not be stored longer than 6 months, due to depletion of vitamin A, D3 and E. Piscivores in human care receive whole fish that were frozen, stored and thawed before feeding. Nutrient losses have been documented, but exact changes during storage and with different thawing methods are unknown. Primarily, it was hypothesized that frozen fish lose different vitamins and trace minerals during a storage period of six months. Secondly, that different thawing methods have a significant influence on the degree of vitamin loss. Three fish species, herring (Clupeus harengus), mackerel (Scomber scombrus) and capelin (Mallotus villosus) were analyzed at four time points within a storage period of 6 months at −20 °C. At each time point, three thawing methods were applied: thawing in a refrigerator (R), thawing at room temperature (RT), and thawing under running water (RW). The following nutrients were analyzed: vitamin A, B1, D3 and E, iron (Fe), copper (Cu), zinc (Zn) and selenium (Se). The statistical method used was a linear mixed effect model. Cu was below detection limits in all analyzed samples, vitamin B1 in most analyzed herring (44/48 samples) and capelin (in 25/36 samples), respectively. In addition, the vitamin D3 concentration was also below detection limits in half of the capelin samples (18/36). No concentration changes of Fe (p = 0.616), Zn (p = 0.686) or Se (p = 0.148) were observed during a storage period of six months, in contrast to a significant decrease in vitamin A (p = 0.019), D3 (p = 0.034) and E (p = 0.003) concentrations. Thawing fish with different thawing methods did not result in concentration changes of Fe (p = 0.821), Zn (p = 0.549) or Se (p = 0.633), but in a significant concentration change of vitamin A (p = 0.002). It is essential to supplement vitamins B1 and E in diets containing whole fish to avoid deficiencies in piscivorous species, and care should be taken not to store fish longer than six months, due to the depletion of vitamins A, D3 and E. [ABSTRACT FROM AUTHOR]

Purpose: The associations between blood retinol, retinol-binding protein (RBP) concentrations and diabetes mellitus were inconsistent in literature. The objective is to investigate these associations by a systematic review and meta-analysis and provide basis for clinical intervention. Methods: PubMed, Web of science, and Cochrane databases were searched from the beginning to July 1, 2021. A total of 13 studies on retinol and 31 studies on RBP are included in the current meta-analysis. Results: The blood retinol concentration was significantly lower in the type I diabetes mellitus (T1DM) [standardized mean difference (SMD) (95% CI): − 0.59 (− 0.81, − 0.37), P < 0.01] and gestational diabetes mellitus (GDM) patients [SMD (95% CI): − 0.54 (− 0.87, − 0.20), P < 0.01] than in the controls. However, the difference was not significant between the type II diabetes mellitus (T2DM) patients and the controls. The RBP concentration was significantly higher in the diabetic patients than in the controls [SMD (95% CI): 0.24 (0.12, 0.35), P < 0.01]. Particularly, the RBP concentration was significantly higher in the T2DM and GDM patients. Conclusion: The blood retinol concentration was negatively associated with T1DM and GDM, while the blood RBP concentration was positively associated with T2DM and GDM. Future work should use a more sensitive retinol measurement method like retinol isotope dilution method to confirm whether blood retinol concentration differs between the diabetes patients and the controls. [ABSTRACT FROM AUTHOR]

The demand for bio-based retinol (vitamin A) is currently increasing, however its instability represents a major bottleneck in microbial production. Here, we developed an efficient method to selectively produce retinol in Yarrowia lipolytica. The β-carotene 15,15′-dioxygenase (BCO) cleaves β-carotene into retinal, which is reduced to retinol by retinol dehydrogenase (RDH). Therefore, to produce retinol, we first generated β-carotene-producing strain based on a high-lipid-producer via overexpressing genes including heterologous β-carotene biosynthetic genes, GGS1 F43I mutant of endogenous geranylgeranyl pyrophosphate synthase isolated by directed evolution, and FAD1 encoding flavin adenine dinucleotide synthetase, while deleting several genes previously known to be beneficial for carotenoid production. To produce retinol, 11 copies of BCO gene from marine bacterium 66A03 (Mb.Blh) were integrated into the rDNA sites of the β-carotene overproducer. The resulting strain produced more retinol than retinal, suggesting strong endogenous promiscuous RDH activity in Y. lipolytica. The introduction of Mb.Blh led to a considerable reduction in β-carotene level, but less than 5% of the consumed β-carotene could be detected in the form of retinal or retinol, implying severe degradation of the produced retinoids. However, addition of the antioxidant butylated hydroxytoluene (BHT) led to a >20-fold increase in retinol production, suggesting oxidative damage is the main cause of intracellular retinol degradation. Overexpression of GSH2 encoding glutathione synthetase further improved retinol production. Raman imaging revealed co-localization of retinol with lipid droplets, and extraction of retinol using Tween 80 was effective in improving retinol production. By combining BHT treatment and extraction using Tween 80, the final strain CJ2104 produced 4.86 g/L retinol and 0.26 g/L retinal in fed-batch fermentation in a 5-L bioreactor, which is the highest retinol production titer ever reported. This study demonstrates that Y. lipolytica is a suitable host for the industrial production of bio-based retinol. • Retinol was produced in Yarrowia lipolytica by metabolic engineering. • First, a β-carotene-overproducing strain was generated from a lipid-overproducer. • Retinol was produced by introducing Mb.Blh into the β-carotene-overproducer. • Retinol stabilization by antioxidant and detergent extraction increased production. • 4.86 g/L retinol was produced with a 95% selectivity over retinal. [ABSTRACT FROM AUTHOR]

Primordial germ cells develop into oocytes and sperm cells. These cells are useful resources in reproductive biology and regenerative medicine. The mesenchymal stem cells (MSCs) have been examined for in vitro production of primordial germ cell-like cells (PGLCs). This study aimed to summarize the existing protocols for MSCs differentiation into PGLCs. In limited identified studies, various models of MSCs, including those derived from adipose tissue, bone marrow, and Wharton's jelly, have been successfully differentiated in to PGLCs. Although the protocols of specification induction are basically very similar, they have been adjusted to the mesenchymal cell type and the species of origin. The availability of MSCs has made it possible to customize conditions for their differentiation into PGLCs in several models, including humans. Refining germ cell-related signaling pathways during induced differentiation of MSCs will help to define extension to the protocols for PGLCs production. [ABSTRACT FROM AUTHOR]

Background: Studies utilizing reflectance confocal microscopy (RCM) and dynamic optical coherence tomography (D‐OCT) to assess cosmetic skin changes are limited. Methods: A 12‐week, open‐label study was conducted using RCM and D‐OCT to evaluate the effects of a topical cosmetic retinol (RET05) on subjects with facial photodamage. Study endpoints included investigator grading, standardized (VISIA‐CR) and 3D photography (Antera 3D), independent RCM (VivaScope1500) and D‐OCT (VivoSight) image analysis, validated FACE‐Q scales, and subject questionnaires. Results: Twenty‐three subjects, 45‐ to 68‐year old, with Fitzpatrick skin types II–IV completed the study. After 12 weeks of repeated application, RET05 demonstrated significant corresponding cosmetic improvements for overall photodamage, skin tone unevenness, tactile roughness, fine lines/wrinkles (forehead, periocular, and perioral), and coarse lines/wrinkles (forehead, periocular, and cheeks), and Allergan Skin Roughness Scale. FACE‐Q assessments also demonstrated significant improvements from baseline at week 12. RCM analysis showed decreases in all epidermis, less compact stratum corneum (SC), more non‐compact SC, decreases in coarse/huddled dermal fibers, and increases in fibrillar dermal fibers, as compared to baseline. D‐OCT analysis showed significant decreases in epidermal thickness (ET), reduction of moderate/many collagen fragments and collagen bundles, and significant increases in the stroma attenuation coefficient and collagen density. Moreover, the dermal–epidermal junction was more pronounced, and vascular abundance at 300 and 500 μm depth increased. Independent evaluation of RCM and D‐OCT images showed similar decreases in ET and improvements in dermal fibers. Conclusion: This study was the first to utilize RCM and D‐OCT to evaluate the cosmetic effects of a topical retinoid and further substantiate improvements in skin quality. [ABSTRACT FROM AUTHOR]