Utilization of diverse protein sources for the development of protein-based nanostructures as bioactive carrier systems: A review of recent research findings (2010-2021).

Consumer awareness of the relationship between health and nutrition has caused a substantial increase in the demand for nutraceuticals and functional foods containing bioactive compounds (BACs) with potential health benefits. However, the direct incorporation of many BACs into commercial food and beverage products is challenging because of their poor matrix compatibility, chemical instability, low bioavailability, or adverse impact on food quality. Advanced encapsulation technologies are therefore being employed to overcome these problems. In this article, we focus on the utilization of plant and animal derived proteins to fabricate micro and nano-particles that can be used for the oral delivery of BACs such as omega-3 oils, vitamins and nutraceuticals. This review comprehensively discusses different methods being implemented for fabrications of protein-based delivery vehicles, types of proteins used, and their compatibility for the purpose. Finally, some of the challenges and limitations of different protein matrices for encapsulation of BACs are deliberated upon. Various approaches have been developed for the fabrication of protein-based microparticles and nanoparticles, including injection-gelation, controlled denaturation, and antisolvent precipitation methods. These methods can be used to construct particle-based delivery systems with different compositions, sizes, surface hydrophobicity, and electrical characteristics, thereby enabling them to be used in a wide range of applications.

Lipid Nanoparticle-mRNA Formulations for Therapeutic Applications.

After decades of extensive fundamental studies and clinical trials, lipid nanoparticles (LNPs) have demonstrated effective mRNA delivery such as the Moderna and Pfizer-BioNTech vaccines fighting against COVID-19. Moreover, researchers and clinicians have been investigating mRNA therapeutics for a variety of therapeutic indications including protein replacement therapy, genome editing, and cancer immunotherapy. To realize these therapeutics in the clinic, there are many formidable challenges. First, novel delivery systems such as LNPs with high delivery efficiency and low toxicity need to be developed for different cell types. Second, mRNA molecules need to be engineered for improved pharmaceutical properties. Lastly, the LNP-mRNA nanoparticle formulations need to match their therapeutic applications.In this Account, we summarize our recent advances in the design and development of various classes of lipids and lipid derivatives, which can be formulated with multiple types of mRNA molecules to treat diverse diseases. For example, we conceived a series of ionizable lipid-like molecules based on the structures of a benzene core, an amide linker, and hydrophobic tails. We identified N1,N3,N5-tris(3-(didodecylamino)propyl)benzene-1,3,5-tricarboxamide (TT3) as a lead compound for mRNA delivery both in vitro and in vivo. Moreover, we tuned the biodegradability of these lipid-like molecules by introducing branched ester or linear ester chains. Meanwhile, inspired by biomimetic compounds, we synthesized vitamin-derived lipids, chemotherapeutic conjugated lipids, phospholipids, and glycolipids. These scaffolds greatly broaden the chemical space of ionizable lipids for mRNA delivery. In another section, we highlight our efforts on the research direction of mRNA engineering. We previously optimized mRNA chemistry using chemically-modified nucleotides to increase the protein expression, such as pseudouridine (ψ), 5-methoxyuridine (5moU), and N1-methylpseudouridine (me1ψ). Also, we engineered the sequences of mRNA 5' untranslated regions (5'-UTRs) and 3' untranslated regions (3'-UTRs), which dramatically enhanced protein expression. With the progress of LNP development and mRNA engineering, we consolidate these technologies and apply them to treat diseases such as genetic disorders, infectious diseases, and cancers. For instance, TT3 and its analog-derived lipid-like nanoparticles can effectively deliver factor IX or VIII mRNA and recover the clotting activity in hemophilia mouse models. Engineered mRNAs encoding SARS-CoV-2 antigens serve well as vaccine candidates against COVID-19. Vitamin-derived lipid nanoparticles loaded with antimicrobial peptide-cathepsin B mRNA enable adoptive macrophage transfer to treat multidrug resistant bacterial sepsis. Biomimetic lipids such as phospholipids formulated with mRNAs encoding costimulatory receptors lead to enhanced cancer immunotherapy.Overall, lipid-mRNA nanoparticle formulations have considerably benefited public health in the COVID-19 pandemic. To expand their applications in clinical use, research work from many disciplines such as chemistry, engineering, materials, pharmaceutical sciences, and medicine need to be integrated. With these collaborative efforts, we believe that more and more lipid-mRNA nanoparticle formulations will enter the clinic in the near future and benefit human health.

LC-MS/MS quantification of fat soluble vitamers - A systematic review.

Fat soluble vitamers (FSV) are several biochemically diverse micronutrients essential for healthy development, growth, metabolism, and cell regulation. We cannot synthesize FSV completely or at the required concentrations. Deficiency or excess of FSV can result in many health problems. Plasma is the most accessible sample matrix for the quantification of FSV. However, due to its complexity and other analytical challenges (e.g., FSV sensitivity to light, oxygen, heat, pH, chemical heterogeneity, standard availability), developing a method for the simultaneous quantification of multiple FSV at physiological concentrations has been challenging. In this systematic review, we examine the parameters and criteria used in existing Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS) methods for FSV quantification to the extraction method, chromatographic resolution, matrix effects, and method validation as critical to a sensitive and robust method. We conclude that the final FSV method sensitivity is predominantly based on aforementioned criteria and future method development using LC-MS/MS will benefit from the application of this systematic review.

Current Understandings of Myeloid Differentiation Inducers in Leukemia Therapy.

Differentiation therapy using all-trans retinoic acid for acute promyelocytic leukemia (APL) is well established. Several attempts have been made to treat non-APL, AML patients by employing differentiation inducers, such as hypomethylating agents (HMAs), and low-dose cytarabine (Ara-C) (LDAC), with encouraging results. Other than HMAs and LDAC, various inducers of myeloid cell differentiation have been identified. This review describes and categorizes these inducers, which include glycosylation modifiers, epigenetic modifiers, vitamin derivatives, cytokines, and chemotherapeutic agents. Some of these inducers are currently being used in clinical trials. I highlight the potential applications of glycosylation modifiers and epigenetic modifiers, which are attracting increasing attention in their use as differentiation therapy against AML. Among the agents described in this review, epigenomic modifiers seem particularly promising, and particular attention should also be paid to glycosylation modifiers. These drugs may signal a new era for AML differentiation therapy.

Smart Vitamin Micelles as Cancer Nanomedicines for Enhanced Intracellular Delivery of Doxorubicin.

Chemotherapy is one of the most effective treatments for cancer. However, intracellular delivery of many anticancer drugs is hindered by their hydrophobicity and low molecular weight. Here, we describe highly biocompatible and biodegradable amphiphilic vitamin conjugates comprising hydrophobic vitamin E and hydrophilic vitamin B labeled with dual pH and glutathione-responsive degradable linkages. Vitamin-based micelles (vitamicelles), formed by self-assembly in aqueous solutions, were optimized based on their stability after encapsulation of doxorubicin (DOX). The resulting vitamicelles have great potential as vehicles for anticancer drugs because they show excellent biocompatibility (>94% after 48 h of incubation) and rapid biodegradability (>90% after 2.5 h). Compared with free DOX, DOX-loaded vitamicelles showed a markedly enhanced anticancer effect as they released the drug rapidly and inhibited drug efflux out of cells efficiently. By exploiting these advantages, this study not only provides a promising strategy for circumventing existing challenges regarding the delivery of anticancer drugs but also extends the utility of current DOX-induced chemotherapy.

Opuntia ficus-indica (L.) Mill.: A Multi-Benefit Potential to Be Exploited.

Consumer interest in foods with enhanced nutritional quality has increased in recent years. The nutritional and bioactive characterization of fruits and their byproducts, as well as their use in the formulation of new food products, is advisable, contributing to decrease the global concerns related to food waste and food security. Moreover, the compounds present in these raw materials and the study of their biological properties can promote health and help to prevent some chronic diseases. Opuntia ficus-indica (L.) Mill. (prickly pear) is a plant that grows wild in the arid and semi-arid regions of the world, being a food source for ones and a potential for others, but not properly valued. This paper carries out an exhaustive review of the scientific literature on the nutritional composition and bioactive compounds of prickly pear and its constituents, as well as its main biological activities and applications. It is a good source of dietary fiber, vitamins and bioactive compounds. Many of its natural compounds have interesting biological activities such as anti-inflammatory, hypoglycemic and antimicrobial. The antioxidant power of prickly pear makes it a good candidate as an ingredient of new food products with fascinating properties for health promotion and/or to be used as natural extracts for food, pharmaceutic or cosmetic applications. In addition, it could be a key player in food security in many arid and semi-arid regions of the world, where there are often no more plants.

Advances in Research on Food Bioactive Molecules and Health.

Fresh and processed food products are rich in bioactive molecules, including polysaccharides, vitamins, carotenoids, peptides, antioxidants, phenolics, phytosterols, and novel lipids. Bioactive molecules in food could prevent several diseases (i.e., metabolic syndrome, cardiovascular diseases, cancer, etc.). Thus, consumer awareness is growing about the health-promoting impact of food bioactive molecules. Health claims are essential added-value features, wherein health-enhancing potential of bioactives depend on their chemical structure. On the other hand, the investigation of the structure-function relationship of food bioactive molecules is of importance. In this regard, Molecules is delighted to highlight the importance of food bioactive molecules and their effect on health. In this Special Issue of Molecules, researchers are invited to contribute original research and up-to-date reviews.

Antioxidants in Potatoes: A Functional View on One of the Major Food Crops Worldwide.

With a growing world population, accelerating climate changes, and limited arable land, it is critical to focus on plant-based resources for sustainable food production. In addition, plants are a cornucopia for secondary metabolites, of which many have robust antioxidative capacities and are beneficial for human health. Potato is one of the major food crops worldwide, and is recognized by the United Nations as an excellent food source for an increasing world population. Potato tubers are rich in a plethora of antioxidants with an array of health-promoting effects. This review article provides a detailed overview about the biosynthesis, chemical and health-promoting properties of the most abundant antioxidants in potato tubers, including several vitamins, carotenoids and phenylpropanoids. The dietary contribution of diverse commercial and primitive cultivars are detailed and document that potato contributes much more than just complex carbohydrates to the diet. Finally, the review provides insights into the current and future potential of potato-based systems as tools and resources for healthy and sustainable food production.

Proteome Analysis and In Vitro Antiviral, Anticancer and Antioxidant Capacities of the Aqueous Extracts of Lentinula edodes and Pleurotus ostreatus Edible Mushrooms.

In this study, we examined aqueous extracts of the edible mushrooms Pleurotus ostreatus (oyster mushroom) and Lentinula edodes (shiitake mushroom). Proteome analysis was conducted using LC-Triple TOF-MS and showed the expression of 753 proteins by Pleurotus ostreatus, and 432 proteins by Lentinula edodes. Bioactive peptides: Rab GDP dissociation inhibitor, superoxide dismutase, thioredoxin reductase, serine proteinase and lectin, were identified in both mushrooms. The extracts also included promising bioactive compounds including phenolics, flavonoids, vitamins and amino acids. The extracts showed promising antiviral activities, with a selectivity index (SI) of 4.5 for Pleurotus ostreatus against adenovirus (Ad7), and a slight activity for Lentinula edodes against herpes simplex-II (HSV-2). The extracts were not cytotoxic to normal human peripheral blood mononuclear cells (PBMCs). On the contrary, they showed moderate cytotoxicity against various cancer cell lines. Additionally, antioxidant activity was assessed using DPPH radical scavenging, ABTS radical cation scavenging and ORAC assays. The two extracts showed potential antioxidant activities, with the maximum activity seen for Pleurotus ostreatus (IC50 µg/mL) = 39.46 ± 1.27 for DPPH; 11.22 ± 1.81 for ABTS; and 21.40 ± 2.20 for ORAC assays. This study encourages the use of these mushrooms in medicine in the light of their low cytotoxicity on normal PBMCs vis à vis their antiviral, antitumor and antioxidant capabilities.

Molecular Simulations suggest Vitamins, Retinoids and Steroids as Ligands of the Free Fatty Acid Pocket of the SARS-CoV-2 Spike Protein*.

We investigate binding of linoleate and other potential ligands to the recently discovered fatty acid binding site in the SARS-CoV-2 spike protein, using docking and molecular dynamics simulations. Simulations suggest that linoleate and dexamethasone stabilize the locked spike conformation, thus reducing the opportunity for ACE2 interaction. In contrast, cholesterol may expose the receptor-binding domain by destabilizing the closed structure, preferentially binding to a different site in the hinge region of the open structure. We docked a library of FDA-approved drugs to the fatty acid site using an approach that reproduces the structure of the linoleate complex. Docking identifies steroids (including dexamethasone and vitamin D); retinoids (some known to be active in vitro, and vitamin A); and vitamin K as potential ligands that may stabilize the closed conformation. The SARS-CoV-2 spike fatty acid site may bind a diverse array of ligands, including dietary components, and therefore provides a promising target for therapeutics or prophylaxis.

Antivitamins B12 -Some Inaugural Milestones.

The recently delineated structure- and reactivity-based concept of antivitamins B12 has begun to bear fruit by the generation, and study, of a range of such B12 -dummies, either vitamin B12 -derived, or transition metal analogues that also represent potential antivitamins B12 or specific B12 -antimetabolites. As reviewed here, this has opened up new research avenues in organometallic B12 -chemistry and bioinorganic coordination chemistry. Exploratory studies with antivitamins B12 have, furthermore, revealed some of their potential, as pharmacologically interesting compounds, for inducing B12 -deficiency in a range of organisms, from hospital resistant bacteria to laboratory mice. The derived capacity of antivitamins B12 to induce functional B12 -deficiency in mammalian cells and organs also suggest their valuable potential as growth inhibitors of cancerous human and animal cells.

Tween 80 and Soya-Lecithin-Based Food-Grade Nanoemulsions for the Effective Delivery of Vitamin D.

Fortification of food and beverages with vitamin D is demanding due to its poor water solubility and oxidation, due to exposure to light and high temperature. The purpose of this research work was to formulate an effective food-grade delivery system for the incorporation of vitamin D into food products and beverages. Food-grade vitamin D nanoemulsions were successfully prepared using mixed surfactant (Tween 80 and soya lecithin) and ultrasonic homogenization techniques. Significant effects (p < 0.05) of temperatures (4 and 25 °C) and storage intervals (1 month) were observed on the turbidity and vitamin D retention. At the end of a 2 month storage, the droplet sizes of the nanoemulsion were 140.15 nm at 4 °C and 155.5 nm at 25 °C. p-Anisidine value of canola oil significantly reduced (p < 0.05) after its incorporation into nanoemulsions. The turbidity values of nanoemulsions increased with the increase in storage duration and temperature. These nanoemulsions remain stable against a wide range of temperatures (30-90 °C), pH values (2-8), ionic strengths (50-400 mM), and freeze-thaw cycles (4 cycles). At the end of 30 days of storage, vitamin D retentions were 74.4 ± 1.2 and 55.3 ± 2.1% in nanoemulsions stored at 4 and 25 °C, respectively. These results suggest that mixed-surfactant-based nanoemulsions are an effective delivery system for the incorporation of vitamin D into food and beverages to overcome the worldwide deficiency of vitamin D.

Synthesis of Gemini analogs of 19-norcalcitriol and their platinum(II) complexes.

Hormonally active vitamin D3 metabolite, calcitriol, plays an important role in calcium-phosphate homeostasis, immune system actions and cell differentiation. Although anticancer activity of calcitriol is well documented and thousands of its analogs have been synthesized, none has been approved as a potential drug against cancer. Therefore, we attempted to introduce the cytotoxic effect to the calcitriol molecule by its linking to cisplatin. Herein, we present the synthesis of vitamin D compounds, designed on the basis of molecular modeling and docking experiments to the vitamin D receptor, and characterized by the presence of significantly different two side chains attached to C-20. In this study, a new synthetic approach to Gemini analogs was developed. Preparation of the target 19-norcalcitriol compounds involved separate syntheses of several building blocks (the A-ring, C/D-rings and side-chain fragments). The convergent synthetic strategy was used to combine these components by the different coupling processes, the crucial one being Wittig-Horner reaction of the Grundmann ketone analog with the known 2-methylene A-ring phosphine oxide. Due to the nature of the constructed steroidal side chains (bidentate ligands), which allowed coordination of metal ions, the first conjugate-type platinum(II) complexes of the vitamin D analogs were also successfully prepared and characterized. The target vitamin D compounds, displaying significant affinity for a vitamin D receptor, were assessed in vitro for their anti-proliferative activities towards several cell lines.

Cis and trans isomers of the vitamin menaquinone-7: which one is biologically significant?

Recently, several studies have indicated that an adequate intake of menaquinone-7 (MK-7) offers numerous health benefits. However, the low availability of MK-7 in the diet necessitates the development of dietary supplements or functional food products to complement natural food sources and meet the daily intake requirements. Like most biological molecules, MK-7 can exist as geometric isomers that can occur in the cis, trans, and cis/trans forms; however, only the all-trans form is biologically significant. MK-7 is traditionally produced through bacterial fermentation, but various synthetic preparations have lately become available. The isomer composition in the final product is influenced by numerous factors, including the methods of production and purification, as well as particular environmental and storage conditions. The MK-7 profile obtained from the various production methods has not yet been elucidated, and the ideal method for the synthesis of the all-trans form of the vitamin is also debatable. Consequently, the quantification of the MK-7 profile of various products is necessary to develop an understanding of the factors that influence the proportion of isomers that are obtained in different preparations. Several possible methods exist for the quantification of MK-7 isomers, and of these, liquid chromatography in conjunction with mass spectrometry techniques appears to be the most promising. Evaluation of the isomer composition is an important consideration, as only the all-trans form sustains biological activity. Furthermore, knowledge of the prominent factors that influence the MK-7 composition may also enable their manipulation to obtain a more favorable MK-7 profile in the final product.

Vitamin E supplementation in people with cystic fibrosis.

BACKGROUND: People with cystic fibrosis are at an increased risk of fat-soluble vitamin deficiency, including vitamin E. Vitamin E deficiency can cause a host of conditions such as haemolytic anaemia, cerebellar ataxia and cognitive difficulties. Vitamin E supplementation is widely recommended for people with cystic fibrosis and aims to ameliorate this deficiency. This is an updated version of the review. OBJECTIVES: To determine the effects of any level of vitamin E supplementation on the frequency of vitamin E deficiency disorders in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Group's Cystic Fibrosis Trials Register and also searched international online trial registries for any ongoing clinical trials that were not identified during our register search. Date of last search of the Register: 11 August 2020. Date of last search of international online trial registries: 20 July 2020. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing any preparation of vitamin E supplementation to placebo or no supplement, regardless of dosage or duration. DATA COLLECTION AND ANALYSIS: Two authors extracted outcome data from each study (published information) and assessed the risk of bias of each included study. They assessed the quality of the evidence using GRADE. MAIN RESULTS: Four studies with a total of 141 participants were included in the review, two of these were in children (aged six months to 14.5 years), and two did not specify participants' age. All studies used different formulations and doses of vitamin E for various durations of treatment (10 days to six months). Two studies compared the supplementation of fat-soluble as well as water-soluble formulations to no supplementation in different arms of the same study. A third study compared a water-soluble formulation to a placebo; and in the fourth study a fat-soluble formulation of vitamin E was assessed against placebo. There was limited detail about randomisation and blinding in the included studies which compromises the quality of the evidence base for the review. The heterogeneous mix of the formulations with differing biovailabilities among these studies also limits the generalisability of the data to the wider cystic fibrosis population. None of the studies in either comparison report the review's primary outcomes of vitamin E total lipid ratio or the incidence of vitamin E-specific deficiency disorders, or the secondary outcomes lung function or quality of life. Water-soluble vitamin E Water-soluble vitamin E may improve serum vitamin E levels compared with control at six months, one study (45 participants), mean difference (MD) 19.74 umol/L (95% confidence interval (CI) 13.48 to 26.00) (low-quality evidence). Similar results were also seen at one month, two studies (32 participants), MD 17.66 umol/L (95% CI 10.59 to 24.74) and at three months, one study (45 participants), MD 11.61 umol/L (95% CI 4.77 to 18.45). Only one study (45 participants) reported weight (secondary outcome of growth and nutritional status) at one and six months, but showed no difference between treatment and control at either time point. Fat-soluble vitamin E Two studies (36 participants) reported higher levels of serum vitamin E at one month with fat-soluble vitamin E compared with control, MD 13.59 umol/L (95% CI 9.52 to 17.66); however, at three months one study (36 participants) showed no difference between treatment and control. No studies in this comparison reported on growth or nutritional status. AUTHORS' CONCLUSIONS: Vitamin E supplementation may lead to an improvement in vitamin E levels in people with cystic fibrosis, although evidence we assessed was low quality. No data on other outcomes of interest were available to allow conclusions about any other benefits of this therapy. In future, larger studies are needed, especially in people already being treated with enteric-coated pancreatic enzymes and supplemented with vitamin E, to look at more specific outcome measures such as vitamin E status, lung function and nutritional status. Future studies could also look at the optimal dose of vitamin E required to achieve maximal clinical effectiveness.

Vitamin C: One compound, several uses. Advances for delivery, efficiency and stability.

Vitamin C (Vit C) is a potent antioxidant with several applications in the cosmetic and pharmaceutical fields. However, the biggest challenge in the utilization of Vit C is to maintain its stability and improve its delivery to the active site. Several strategies have been developed such as: controlling the oxygen levels during formulation and storage, low pH, reduction of water content in the formulation and the addition of preservative agents. Additionally, the utilization of derivatives of Vit C and the development of micro and nanoencapsulated delivery systems have been highlighted. In this article, the multiple applications and mechanisms of action of vitamin C will be reviewed and discussed, as well as the new possibilities of delivery and improvement of stability.

Protection from Ultraviolet Damage and Photocarcinogenesis by Vitamin D Compounds.

Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds.

The Role of Classical and Novel Forms of Vitamin D in the Pathogenesis and Progression of Nonmelanoma Skin Cancers.

Nonmelanoma skin cancers including basal and squamous cell carcinomas (SCC and BCC) represent a significant clinical problem due to their relatively high incidence, imposing an economic burden to healthcare systems around the world. It is accepted that ultraviolet radiation (UVR: λ = 290-400 nm) plays a crucial role in the initiation and promotion of BCC and SCC with UVB (λ = 290-320 nm) having a central role in this process. On the other hand, UVB is required for vitamin D3 (D3) production in the skin, which supplies >90% of the body's requirement for this prohormone. Prolonged exposure to UVB can also generate tachysterol and lumisterol. Vitamin D3 itself and its canonical (1,25(OH)2D3) and noncanonical (CYP11A1-intitated) D3 hydroxyderivatives show photoprotective functions in the skin. These include regulation of keratinocyte proliferation and differentiation, induction of anti-oxidative responses, inhibition of DNA damage and induction of DNA repair mechanisms, and anti-inflammatory activities. Studies in animals have demonstrated that D3 hydroxyderivatives can attenuate UVB or chemically induced epidermal cancerogenesis and inhibit growth of SCC and BCC. Genomic and non-genomic mechanisms of action have been suggested. In addition, vitamin D3 itself inhibits hedgehog signaling pathways which have been implicated in many cancers. Silencing of the vitamin D receptor leads to increased propensity to develop UVB or chemically induced epidermal cancers. Other targets for vitamin D compounds include 1,25D3-MARRS, retinoic orphan receptors α and γ, aryl hydrocarbon receptor, and Wnt signaling. Most recently, photoprotective effects of lumisterol hydroxyderivatives have been identified. Clinical trials demonstrated a beneficial role of vitamin D compounds in the treatment of actinic keratosis. In summary, recent advances in vitamin D biology and pharmacology open new exciting opportunities in chemoprevention and treatment of skin cancers.

Short communication: Influence of intramuscular injection of vitamin B12 in early-lactation dairy cows on Mozzarella cheese quality and vitamin B12 stability.

The current study explored the effect of intramuscular injection of vitamin B12 (VB12) in early-lactation dairy cows on subsequent low-moisture part-skim Mozzarella cheese quality and VB12 levels during cheese processing and storage. Twenty-four peripartum dairy cows were blocked based on parity and milk yield and randomly assigned into 2 treatments: basal diet (CON) and basal diet with an intramuscular injection of 10 mg of VB12 per cow per week (VB12). Raw milk was collected to determine VB12 content and then used to make low-moisture part-skim Mozzarella cheese 8 wk after injection. The VB12 content of raw milk and cheese was determined using ultra-performance liquid chromatography coupled with tandem mass spectrometry. We found that VB12 content was significantly increased in milk (15.43 vs. 3.30 ng/mL) and fresh cheese (3.72 ng/g vs. undetectable) from the VB12 group compared with the CON group. However, approximately 70% of VB12 was lost in the whey during cheese making, and no VB12 was detectable in either cheese treatment after 8 wk of storage. Furthermore, no significant differences were observed in fat and protein contents in the cheese between the 2 groups. For cheese color, the b* value increased and the a* value decreased slightly in fresh VB12 cheese. Functional properties of stretchability, flowability, and meltability of VB12 cheese were initially comparable to that of CON cheese, but higher flowability and meltability was observed in VB12 cheese after 8 wk of storage. In summary, intramuscular injection of VB12 in early-lactation dairy cows increases the content of VB12 in milk and fresh cheese with no adverse effect on cheese quality, but substantial VB12 is lost during cheesemaking and declines rapidly during storage.

Evidence of a possible therapeutic role of vitamin D in a cohort of adult Caucasian vitiligo patients.

Reduced serum 25(OH)D levels have been largely reported in vitiligo, which is an autoimmune skin disorder characterized by the appearance of achromic macules. Since vitamin D can positively modulate immune function and stimulate melanogenesis in vitro, a possible role of sufficient vitamin D levels in promoting the stability of the disease and repigmentation process might be hypothesized in vitiligo. Hence, we conducted an observational study on medical records related to 101 vitiligo patients, in order to correlate baseline 25(OH)D levels with the baseline vitiligo activity and repigmentation of vitiligo macules on a 6-month follow-up. According to our results, at baseline we found that active vitiligo was significantly associated with 25(OH)D deficiency (≤20 ng/mL) (P = 0.036) or insufficiency (21-29 ng/mL) (P = 0.041), while stable disease was significantly associated with sufficient 25(OH)D levels (30-100 ng/mL) (P = 0.043). After 6 months, vitiligo patients with sufficient 25(OH)D levels (30-100 ng/mL) achieved a significantly higher degree of repigmentation. In conclusion, our study provides a novel evidence of a significant positive association of sufficient 25(OH)D levels with the stability of the disease and a satisfactory repigmentation process in Caucasian adult vitiligo patients and strengthen the need to assess vitamin D status in vitiligo. The correlation between sufficient vitamin D levels and a satisfactory course of the disease opens the way for future randomized controlled trials assessing a possible beneficial role of vitamin D supplementation on vitiligo.