Search Results (35)

Background: Acne scars remain a very common complaint in dermatology practices. Even though many treatment options are available, proper treatment remains a challenge. Complex treatment methods that are based on the synergy effect are the ones that result in better effects and patient satisfaction. Methods: Three healthy female patients with a total of 106 atrophic acne scars were recruited to the split-face study with placebo control, where a series of three microneedling procedures in monthly intervals combined with 5% retinyl palmitate-loaded oleogel was compared to the same microneedling protocol with placebo. Patients’ quality of life was measured using the Dermatology Life Quality Index (DLQI) and Skindex-29 questionnaires. Patients’ satisfaction with treatment and intensity of post-procedure symptoms were assessed as well. Results: In clinical evaluation, a modest effect was observed regarding the reduction in atrophic acne scars, whereas moderate-to-marked improvement in acne scar reduction was noted by the patients. Additionally, mild to marked improvement was noted by patients regarding skin quality, moisture level, elasticity, and skin tone. No significant side effects were noted. All the above resulted in good patient satisfaction with the treatment, and willingness to repeat the procedures again. No significant differences regarding acne scar reduction, treatment-related symptoms, and skin quality improvement were noted between active substance and placebo-treated sides of the face. Conclusions: Microneedling remains a key method in the therapeutic arsenal for acne scarring. By combining it with 5% retinyl palmitate-loaded oleogel modest effects can be noted after a series of three procedures, with good overall treatment tolerability and patients’ satisfaction. Full article

Vitamin A in the form of 11-cis-retinaldehyde is the chromophore essential to vision. Thus, deficiencies in vitamin A necessitate the implementation of vitamin A supplementation. Moreover, some vitamin A is lost from the visual cycle due to random reactions that generate diretinaldehyde (bisretinoid) molecules; the latter are photoreactive and contribute to retinal disease. Here, we measured the systemic and ocular uptake of vitamin A along with bisretinoid as a function of vitamin A availability when supplied in the diet or by weekly i.p. injection in light- and dark-reared mice. Retinyl palmitate delivered as an i.p. bolus served to elevate plasma ROL but an associated increase in ocular 11-cisRAL was not observed in light- or dark-reared mice. In dark-reared mice, 11-cisRAL was more abundant when retinyl palmitate was provided in chow versus weekly i.p. injection; moreover, by the latter route, retinyl acetate was more effective. Conversely in dark-reared mice given retinyl palmitate by weekly i.p. injection versus chow, ocular atRAL was elevated. Liver atRE was elevated by increased retinyl palmitate in chow; the latter also favored elevated 11-cisRAL in dark-reared mice. In cyclic light-reared mice, ocular stores of atRE were increased by i.p. retinyl palmitate. With dark-rearing, there was no difference in bisretinoid (A2E) with retinyl palmitate in chow, nor by weekly i.p. injection; notably, bisretinoid levels were lower in cyclic light-reared mice due to photooxidative loss. In summary, light modulates the ocular retinoid, plasma atROL does not predict ocular levels of retinoid or bisretinoid and atRAL is elevated with sustained darkness. Full article

Skin photoageing remains a topic of considerable concern. Retinol (RT) and retinyl palmitate (RP) have shown preliminary therapeutic efficacy; nevertheless, the high irritation associated with RT and the relatively modest efficacy of RP have constrained their broader application. Consequently, this study explored the effects and biosafety of RT and RP in repairing UV-induced skin ageing through a series of in vitro cell experiments, in vitro hemolysis assays, UV-irradiated mouse models, and molecular simulation techniques. The findings revealed that the interaction between RT and RP achieved complementary and enhanced therapeutic outcomes. Specifically, this combination improved the biosafety profile of retinoid formulations, accelerated cell migration rates, and facilitated the activation of the peroxisome proliferator-activated receptor α (PPARα) pathway. Moreover, the action of RT and RP further mitigated epidermal hyperplasia, mast cell infiltration, and the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α), while stimulating the synthesis of type I collagen. Metabolomics and transcriptomics analyses indicated that RT and RP exerted complementary effects through metabolic pathways, significantly elevating the overall therapeutic efficacy. Network pharmacology and molecular docking studies unveiled that the structural similarity between RT and RP was one of the contributors to their enhancement. In conclusion, this study demonstrated that the combined application of RT and RP exhibited marked effects. Through their mutual action, they not only potentiated each other’s therapeutic effects but also achieved complementary and optimised therapeutic outcomes, thereby substantially enhancing the overall efficacy. Full article

Previous studies have shown that high-dose vitamin supplements can improve vaccine-induced immune responses and pathogen protection in the context of vitamin deficiencies. To further elucidate the influence of vitamin supplements on immune responses toward pediatric vaccines, we performed a randomized controlled clinical trial (PCVIT) of 20 healthy children 1–4 years of age in Memphis, Tennessee. Study participants received a booster vaccine for pneumococcus and a primary vaccine for hepatitis A virus with or without a high-dose, oral, liquid supplement of 10,000 IU retinyl palmitate. We found that the children enrolled in PCVIT had higher baseline vitamin levels than previously described older children and adults living in Memphis. Only one child in PCVIT had a serum retinol level of less than 0.3 µg/mL. The children frequently consumed milk and baby foods that were likely vitamin-fortified, providing an explanation for the relatively high vitamin levels. Most children in PCVIT responded well to pneumococcus and hepatitis A vaccines by pathogen-specific antibody upregulation. The one child with a serum retinol level below 0.3 µg/mL did not receive a vitamin supplement and exhibited the lowest fold-change in antibody responses toward pneumococcal serotypes. A correlation matrix encompassing demographics, vitamin levels, vaccine-induced immune responses, C-reactive protein, and total serum immunoglobulin isotypes, including IgG2 and IgA, identified variables associated with vaccination outcomes. Perhaps because children were predominantly retinol-sufficient at baseline, the high-dose vitamin A supplement exhibited no benefit to vaccine-induced immune responses. In fact, when vitamin supplemented and vitamin unsupplemented groups were compared among participants with the highest baseline retinol levels, there was a trend toward weaker vaccine-induced immune responses in the vitamin supplemented group. Results encourage the performance of larger clinical studies before high-dose vitamin supplements are recommended for populations that are otherwise vitamin-replete. Full article

Intravaginal drug administration offers several advantages over other routes, primarily bypassing the initial stages of metabolism. Additionally, this route has demonstrated both local and systemic effects. Mucoadhesive polymeric systems can be utilized to prevent dose loss due to the mucous barriers and the formation of wet cavities. This study employed various techniques to evaluate the performance and characteristics of a mucoadhesive film composed of HPMC-PEG 400 containing retinyl palmitate and ketorolac molecules. Scanning Electron Microscopy (SEM) was employed to analyze the porous structure of the film. Thermogravimetric Analysis (TGA) was conducted at different temperatures to assess thermal stability. Fourier Transform Infrared Spectroscopy (FTIR) was used to analyze the functional groups and intermolecular interactions between the film and the drug. Swelling and weight loss tests indicated that the film disintegrated within 3–4 days. UV-VIS spectroscopy was used for drug release evaluation based on the Higuchi equation. Additionally, the surface wetting properties were assessed through contact angle measurements. The system’s biocompatibility was confirmed using the MTT assay. Finally, adhesion and glide tests demonstrated the film’s interaction with porcine uterine tissue. This study shows that the HPMC-PEG 400 film containing retinyl palmitate molecules interacts effectively with tissue and could be considered a novel tool for treating damaged epithelial tissues. Full article

Accurate estimation of food intake is necessary to clarify the relationship between dietary intake and particular health conditions; however, self-reported assessments often result in estimation errors. In addition, increasing evidence indicates an association between a higher intake of fruits and vegetables and a lower risk of some diseases, and many countries are encouraging their consumption. Biomarkers of vegetable and fruit intake are important tools for objectively estimating dietary intake in nutritional epidemiological studies. To determine the association between vegetable and fruit intake and blood biomarkers, we systematically reviewed relevant literature on Asians. Databases, PubMed, and CiNii Articles were searched for English and Japanese articles. Of the 91 articles retrieved, 4 were selected for review, including 2 cross-sectional studies, 1 longitudinal study, and 1 randomized trial. Our literature review showed that vegetable consumption is positively associated with plasma concentrations of γ-tocopherol, β-cryptoxanthin, α-carotene, β-carotene, lutein, threonate, galactarate, creatine, and ascorbic acid. In comparison, fruit consumption is positively associated with blood concentrations of α-tocopherol, β-cryptoxanthin, α-carotene, β-carotene, lycopene, retinyl palmitate, ascorbic acid, proline betaine, threonate, and galactarate. Therefore, blood β-carotene, β-cryptoxanthin, and ascorbic acid concentrations may be useful biomarkers for predicting vegetable and fruit intake in Asian population. Full article

Topical and transdermal drug delivery are advantageous administration routes, especially when treating diseases and conditions with a skin etiology. Nevertheless, conventional dosage forms often lead to low therapeutic efficacy, safety issues, and patient noncompliance. To tackle these issues, novel topical and transdermal platforms involving nanotechnology have been developed. This review focuses on the latest advances regarding the development of nanoemulgels for skin application, encapsulating a wide variety of molecules, including already marketed drugs (miconazole, ketoconazole, fusidic acid, imiquimod, meloxicam), repurposed marketed drugs (atorvastatin, omeprazole, leflunomide), natural-derived compounds (eucalyptol, naringenin, thymoquinone, curcumin, chrysin, brucine, capsaicin), and other synthetic molecules (ebselen, tocotrienols, retinyl palmitate), for wound healing, skin and skin appendage infections, skin inflammatory diseases, skin cancer, neuropathy, or anti-aging purposes. Developed formulations revealed adequate droplet size, PDI, viscosity, spreadability, pH, stability, drug release, and drug permeation and/or retention capacity, having more advantageous characteristics than current marketed formulations. In vitro and/or in vivo studies established the safety and efficacy of the developed formulations, confirming their therapeutic potential, and making them promising platforms for the replacement of current therapies, or as possible adjuvant treatments, which might someday effectively reach the market to help fight highly incident skin or systemic diseases and conditions. Full article

In the retina, retinoids involved in vision are under constant threat of oxidation, and their oxidation products exhibit deleterious properties. Using pulse radiolysis, this study determined that the bimolecular rate constants of scavenging cation radicals of retinoids by taurine are smaller than 2 × 10⁷ M⁻¹s⁻¹ whereas lutein scavenges cation radicals of all three retinoids with the bimolecular rate constants approach the diffusion-controlled limits, while zeaxanthin is only 1.4–1.6-fold less effective. Despite that lutein exhibits greater scavenging rate constants of retinoid cation radicals than other antioxidants, the greater concentrations of ascorbate in the retina suggest that ascorbate may be the main protectant of all visual cycle retinoids from oxidative degradation, while α-tocopherol may play a substantial role in the protection of retinaldehyde but is relatively inefficient in the protection of retinol or retinyl palmitate. While the protection of retinoids by lutein and zeaxanthin appears inefficient in the retinal periphery, it can be quite substantial in the macula. Although the determined rate constants of scavenging the cation radicals of retinol and retinaldehyde by dopa-melanin are relatively small, the high concentration of melanin in the RPE melanosomes suggests they can be scavenged if they are in proximity to melanin-containing pigment granules. Full article

Wheat bran can be used as a cost-effective food ingredient to stabilise vitamin A. However, wheat bran endogenous enzymes have been shown to reduce vitamin A stability. In this study, we elucidated the mechanism for this negative effect in an accelerated storage experiment with model systems consisting of native or toasted wheat bran, soy oil and retinyl palmitate (RP). Both native and toasted wheat bran substantially stabilised RP. While RP was entirely degraded after ten days of storage in the absence of wheat bran, the RP retention after ten days was 22 ± 2% and 75 ± 5% in the presence of native and toasted bran, respectively. The significantly stronger stabilising effect of toasted bran was attributed to the absence of bran endogenous enzymes. In contrast to toasted bran systems, noticeable free fatty acid production was observed for native bran systems. However, this did not result in a pronounced lipid oxidation. Next to lipid hydrolysis, wheat bran lipase was shown to hydrolyse retinyl esters to the less stable retinol and fatty acids. This reaction could explain the major part, about 66 ± 5%, of the difference in RP stabilisation between native and toasted wheat bran. Full article

Retinyl palmitate (RP) is a retinol ester with strong antioxidant and anti-inflammatory properties as an antiwrinkle agent. However, it has poor aqueous solubility and easily degrades into inactive forms for topical applications. Therefore, we developed chitosan-coated nanocapsules (ChiNCs) to encapsulate RP using a simple nanoprecipitation method for protection against physiological conditions and to enable deep skin penetration. The as-prepared RP-loaded nanocapsules (RP@ChiNCs) loaded with approximately 5 wt.% RP exhibited a hydrodynamic diameter of 86 nm and surface charge of 24 mV. They had adequate stability to maintain their physicochemical properties after lyophilization in a biological buffer. Notably, ChiNCs provided RP with remarkable protection against degradation for 4 weeks at 37 °C. Thus, RP@ChiNCs exhibited good antioxidant activity in situ for sufficiently long periods without considerable changes in their efficacy. Furthermore, ChiNCs enhanced the skin penetration of lipophilic RP based on the inherent nature of chitosan. RP@ChiNCs exhibited good in vitro antioxidant and anti-inflammatory effects without causing any cytotoxicity in dermal fibroblasts. Accordingly, they promoted cell proliferation in a wound-scratch test and enhanced collagen synthesis. These results suggest that RP@ChiNCs are promising candidates for cosmetic and biomedical applications. Full article

Approximately 5–20% of HNSCC patients experience second primary cancers within the first 5 years of treatment, contributing to high mortality rates. Epidemiological evidence has linked a low dietary intake of antioxidants to an increased risk of cancer, especially squamous cell carcinoma, prompting research into their potential in neoplasm chemoprevention. Cigarette smoking is the primary risk factor for HNSCC, and a diet rich in antioxidants offers protective effects against head and neck cancer. Paradoxically, smokers, who are at the highest risk, tend to consume fewer antioxidant-rich fruits and vegetables. This has led to the hypothesis that integrating antioxidants into the diet could play a role in both primary and secondary prevention for at-risk individuals. Furthermore, some HNSCC patients use antioxidant supplements during chemotherapy or radiotherapy to manage side effects, but their impact on cancer outcomes remains uncertain. This systematic review explores the evidence for the potential use of antioxidants in preventing second primary cancers in HNSCC patients. In conclusion, none of the antioxidants tested so far (α-tocopherol, β-carotene, JP, Isotretinoin, interferon α-2a, vitamin E, retinyl palmitate, N-acetylcysteine) was effective in preventing second primary tumors in HNSCC patients, and they could only be used in reducing the side effects of radiotherapy. Further research is needed to better understand the interplay between antioxidants and cancer outcomes in this context. Full article

Dietary deficiencies in zinc (Zn) and vitamin A (VA) are among the leading micronutrient deficiencies globally and previous research has proposed a notable interaction between Zn and VA physiological status. This study aimed to assess the effects of zinc and vitamin A (isolated and combined) on intestinal functionality and morphology, and the gut microbiome (Gallus gallus). The study included nine treatment groups (n~11)—no-injection (NI); H₂O; 0.5% oil; normal zinc (40 mg/kg ZnSO₄) (ZN); low zinc (20 mg/kg) (ZL); normal retinoid (1500 IU/kg retinyl palmitate) (RN); low retinoid (100 IU/kg) (RL); normal zinc and retinoid (40 mg/kg; 1500 IU/kg) (ZNRN); low zinc and retinoid (ZLRL) (20 mg/kg; 100 IU/kg). Samples were injected into the amniotic fluid of the fertile broiler eggs. Tissue samples were collected upon hatch to target biomarkers. ZLRL reduced ZIP4 gene expression and upregulated ZnT1 gene expression (p < 0.05). Duodenal surface area increased the greatest in RL compared to RN (p < 0.01), and ZLRL compared to ZNRN (p < 0.05). All nutrient treatments yielded shorter crypt depths (p < 0.01). Compared to the oil control, ZLRL and ZNRN reduced (p < 0.05) the cecal abundance of Bifidobacterium and Clostridium genera (p < 0.05). These results suggest a potentially improved intestinal epithelium proceeding with Zn and VA intra-amniotic administration. Intestinal functionality and gut bacteria were modulated. Further research should characterize long-term responses and the microbiome profile. Full article

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. Full article

In the present study, gastro-resistant microparticles (MPs) were produced using the spray-drying technique as controlled-release systems for some model liposoluble vitamins, including retinyl-palmitate, retinyl-acetate, β-carotene, cholecalciferol and α-tocopherol. The gastroprotective action of three different gastro-resistant excipients, the anionic methacrylic copolymer (Eudraguard^®® Biotic, E1207), the cellulose acetate phthalate (CAP) and whey proteins (WPs), was compared. The latter was used to produce a novel delivery system manufactured with only food-derived components, such as milk, and showed several improvements over the two synthetic gastro-resistant agents. Scanning electron microscopy (SEM) images showed a quite homogeneous spherical shape of all microparticle batches, with an average diameter between 7 and 15 μm. FTIR analysis was used to evaluate the effective incorporation of vitamins within the microparticles and the absence of any degradation to the components of the formulation. The comparison graphs of differential scanning calorimetry (DSC) confirmed that the spray drying technique generates a solid in which the physical interactions between the excipients and the vitamins are very strong. Release studies showed a prominent pH-controlled release and partially a delayed-release profile. Ex vivo permeation studies of retinyl palmitate, retinyl acetate and α-tocopherol revealed greater transmucosal permeation capacity for microparticles produced with the WPs and milk. Full article