Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.348
Filtrar
1.
Iran J Allergy Asthma Immunol ; 21(4): 429-440, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36243931

RESUMO

Vitamins A, D, and microRNAs contribute to T cell differentiation into TH2 phenotypes. We investigated the molecular mechanisms and effects of vitamin A and D on the expression of GATA3 and miR-27-3p isoforms in experimental autoimmune encephalomyelitis (EAE) animal model of multiple sclerosis. EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein, mixed with Complete Freund's Adjuvant, together with injection of pertussis toxin. Treatments began one day before immunization with (200 µg and 100 ng of vitamin A and vitamin D per mouse, respectively, and vitamin A+D (100 µg+50 ng) per mouse. Expression levels of GATA3 and miR­27­3p isoforms were measured in the CNS and splenocytes by real-time RT-PCR. The expression level of GATA3 in the mice spinal cords and splenocytes was increased in the vitamin A and A+D-treated EAE mice at 24 h and 48 h after restimulation by 10 µg and 40 µg of myelin oligodendrocyte glycoprotein. Vitamins A and D and their combination upregulated the miR-27-3p isoforms compared with EAE mice with no treatments. We also demonstrated that miR-273p isoform expression was altered in splenocytes of vitamin-treated EAE mice. The results showed a positive correlation between splenocyte GATA3 levels and miR-27-3p isoform expression. The protective impacts of vitamins A and D in EAE mice may be mediated by the upregulation of GATA3. However, it is not specified whether suppression of GATA3-targeting miRNAs of the miR-27-3p family is involved in this effect. These results do not rule out the possibility that miR-27-3p isoforms might have beneficial effects by targeting other transcripts, such as GluA2 and NR2B.


Assuntos
Encefalomielite Autoimune Experimental , MicroRNAs , Animais , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/genética , Adjuvante de Freund , Fator de Transcrição GATA3/genética , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Glicoproteína Mielina-Oligodendrócito , Toxina Pertussis , Isoformas de Proteínas/genética , Vitamina A/farmacologia , Vitamina D , Vitamina K , Vitaminas
2.
Cells ; 11(18)2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36139415

RESUMO

Extending well beyond the original use of propagating neural precursors from the central nervous system and dorsal root ganglia, neurosphere medium (NSM) and self-renewal medium (SRM) are two distinct formulas with widespread popularity in enteric neural stem cell (ENSC) applications. However, it remains unknown what growth factors or nutrients are crucial to ENSC development, let alone whether the discrepancy in their components may affect the outcomes of ENSC culture. Dispersed enterocytes from murine fetal gut were nurtured in NSM, SRM or their modifications by selective component elimination or addition to assess their effects on ENSC development. NSM generated neuriteless neurospheres, whereas SRM, even deprived of chicken embryo extract, might wire ganglia together to assemble neural networks. The distinct outcomes came from epidermal growth factor, which inhibited enteric neuronal wiring in NSM. In contrast, basic fibroblast growth factor promoted enteric neurogenesis, gangliogenesis, and neuronal wiring. Moreover, vitamin A derivatives might facilitate neuronal maturation evidenced by p75 downregulation during ENSC differentiation toward enteric neurons to promote gangliogenesis and network assembly. Our results might help to better manipulate ENSC propagation and differentiation in vitro, and open a new avenue for the study of enteric neuronal neuritogenesis and synaptogenesis.


Assuntos
Fator de Crescimento Epidérmico , Fator 2 de Crescimento de Fibroblastos , Rede Nervosa , Vitamina A , Animais , Células Cultivadas , Embrião de Galinha , Fator de Crescimento Epidérmico/farmacologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Camundongos , Rede Nervosa/crescimento & desenvolvimento , Vitamina A/farmacologia
3.
Biomed Pharmacother ; 155: 113678, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36108391

RESUMO

The vitamin A metabolite all-trans retinoic acid (ATRA; tretinoin) has anticancer potential. However, lack of clinical success has prevented its approval for solid tumours. Herein, we propose combining short-term low-dose ATRA with fimaporfin-based photodynamic therapy (ATRA+PDT) for the improved treatment of solid cancers. Compared to monotherapies, ATRA+PDT induced synergistic cytotoxic responses including promotion of apoptosis in colon and breast carcinoma cell lines. Neither enhanced activity of alkaline phosphatase (ALP) nor increased expression of CD133 was detected after ATRA treatment indicating that the improved therapeutic effect of ATRA+PDT is independent of the differentiation state of the cancer cells. In the human colorectal adenocarcinoma cell line HT-29, the effect of ATRA+PDT on gene expression was evaluated by RNA sequencing (RNA-seq). We identified 1129 differentially expressed genes (DEGs) after ATRA+PDT compared to PDT. Ingenuity Pathway Analysis (IPA) predicted the unfolded protein response (UPR), interferon (IFN) signaling and retinoic acid-mediated apoptosis signaling as strongly activated canonical pathways after ATRA+PDT compared to PDT. A validation of the RNA-sec data by RT-qPCR revealed that ATRA+PDT elevated mRNA expression of early growth response 1 (EGR1) and strongly the stress-induced activating transcription factor 3 (ATF3), of which was confirmed on the protein level. In addition, ATRA+PDT abolished mRNA expression of regenerating islet-derived protein 4 (REG4). During the first 20 days post-ATRA+PDT, we obtained significant anti-tumour responses in HT-29 xenografts, including complete responses in 2/5 mice. In conclusion, ATRA+PDT represent a novel combination therapy for solid tumours that should be further tested in immunocompetent preclinical models.


Assuntos
Fotoquimioterapia , Vitamina A , Humanos , Camundongos , Animais , Vitamina A/farmacologia , Fator 3 Ativador da Transcrição , Fosfatase Alcalina , Proteínas Associadas a Pancreatite , Tretinoína/farmacologia , Apoptose , RNA Mensageiro , Interferons/farmacologia , RNA , Linhagem Celular Tumoral
4.
Int J Mol Sci ; 23(16)2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36012634

RESUMO

Previously, we established a highly sensitive promoter-trapping vector system using the piggyBac transposon for the efficient isolation of reporter cells. Herein, we examine whether this screening system can be applied to obtain vitamin-responsive cells. As a result, one and two reporter cells that responded to bexarotene (vitamin A) and calcitriol (vitamin D), respectively, were isolated from 4.7 × 106 seeded HeLaS3 cells. 5' RACE analyses identified the well-known CYP24A1 gene as a calcitriol-responsive gene, as well as two new bexarotene- or calcitriol-responsive genes, BDKRB2 and TSKU, respectively. TSKU, interestingly, also responded to bexarotene. Endogenous levels of the TSKU and BDKRB2 transcripts displayed only slight changes and were not detected in the comprehensive analyses performed to date. Dose-response analyses of BDKRB2 and TSKU reporter cells in parallel revealed a differential profile in response to each vitamin A agonist, suggesting a bioanalyzer. The present study demonstrates that producing multiple reporter cells by a type of random screening can efficiently identify novel genes with unusual characteristics and be used for the profiling of the properties of vitamin compounds. Similar approaches to the method shown here may be useful for identifying new markers and for the analysis or diagnosis of nutrients, toxins, metabolites, etc.


Assuntos
Calcitriol , Vitamina A , Bexaroteno , Calcitriol/metabolismo , Genes Reporter , Regiões Promotoras Genéticas , Receptores de Calcitriol/metabolismo , Vitamina A/farmacologia , Vitaminas/farmacologia
5.
ACS Nano ; 16(9): 14029-14042, 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36036898

RESUMO

During liver fibrogenesis, liver sinusoidal capillarization and extracellular matrix (ECM) deposition construct dual pathological barriers to drug delivery. Upon capillarization, the vanished fenestrae in liver sinusoidal endothelial cells (LSECs) significantly hinder substance exchange between blood and liver cells, while excessive ECM further hinders the delivery of nanocarriers to activated hepatic stellate cells (HSCs). Herein, an efficient nanodrug delivery system was constructed to sequentially break through the capillarized LSEC barrier and the deposited ECM barrier. For the first barrier, LSEC-targeting and fenestrae-repairing nanoparticles (named HA-NPs/SMV) were designed on the basis of the modification with hyaluronic acid and the loading of simvastatin (SMV). For the second barrier, collagenase I and vitamin A codecorated nanoparticles with collagen-ablating and HSC-targeting functions (named CV-NPs/siCol1α1) were prepared to deliver siCol1α1 with the goal of inhibiting collagen generation and HSC activation. Our in vivo results showed that upon encountering the capillarized LSEC barrier, HA-NPs/SMV rapidly released SMV and exerted a fenestrae-repairing function, which allowed more CV-NPs/siCol1α1 to enter the space of Disse to degrade deposited collagen and finally to achieve higher accumulation in activated HSCs. Scanning electronic microscopy images showed the recovery of liver sinusoids, and analysis of liver tissue sections demonstrated that HA-NPs/SMV and CV-NPs/siCol1α1 had a synergetic effect. Our pathological barrier-normalization strategy provides an antifibrotic therapeutic regimen.


Assuntos
Capilares , Células Endoteliais , Capilares/metabolismo , Capilares/patologia , Colagenases/farmacologia , Células Endoteliais/metabolismo , Matriz Extracelular/metabolismo , Células Estreladas do Fígado/metabolismo , Humanos , Ácido Hialurônico/farmacologia , Fígado/metabolismo , Cirrose Hepática/metabolismo , Sinvastatina/metabolismo , Sinvastatina/farmacologia , Vitamina A/metabolismo , Vitamina A/farmacologia
6.
PLoS One ; 17(7): e0269585, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35793308

RESUMO

The increase in the area cultivated with vitamin-enriched transgenic crops producing Bt toxin raises the question of whether the addition of vitamins will in any way mitigates the effect of the toxin on the phytophagous insects that feed on those crops. On the other hand, the parental effect that feeding on these enriched transgenic crops may have on the offspring of the phytophagous that survive on them is not well known. In this work, the effect of vitamin A (ß-carotene) addition to diets with or without Bt toxin on Helicoverpa armigera larvae and their offspring was determined. The addition of vitamin A did not have any beneficial effect either for the larvae fed on enriched diets nor for their offspring. However, parental effects due to dietary feeding with the toxin were detected since adults from larvae fed on the Bt diet had higher mating success than those fed on the toxin-free diet, although there were no differences on the fertility of mated females regardless of whether their previous larvae fed on the Bt or non-Bt diet. A certain adaptive effect to the toxin was also noted since the mortality of larvae whose previous generation fed on diet with Bt was lower than that of the larvae that came from larvae fed on a non-Bt diet. It would be interesting to determine if H. armigera adults prefer to mate and lay eggs in the same type of crops in which they have developed or if feeding on different crops, such as corn or alfalfa, causes different paternal effects on the offspring. These aspects can be of great importance in the development of resistance of this species to the Bt toxin.


Assuntos
Toxinas de Bacillus thuringiensis , Mariposas , Animais , Proteínas de Bactérias/farmacologia , Produtos Agrícolas , Endotoxinas/farmacologia , Proteínas Hemolisinas/farmacologia , Larva , Vitamina A/farmacologia
7.
Mar Drugs ; 20(7)2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35877726

RESUMO

Vitamin A and provitamin A carotenoids are involved in the regulation of adipose tissue metabolism and inflammation. We examined the effect of dietary supplementation using all-trans and 9-cis ß-carotene-rich Dunaliella bardawil alga as the sole source of vitamin A on obesity-associated comorbidities and adipose tissue dysfunction in a diet-induced obesity mouse model. Three-week-old male mice (C57BL/6) were randomly allocated into two groups and fed a high-fat, vitamin A-deficient diet supplemented with either vitamin A (HFD) or ß-carotene (BC) (HFD-BC). Vitamin A levels in the liver, WATs, and BAT of the HFD-BC group were 1.5-2.4-fold higher than of the HFD group. BC concentrations were 5-6-fold greater in BAT compared to WAT in the HFD-BC group. The eWAT mRNA levels of the Mcp-1 and Cd68 were 1.6- and 2.1-fold lower, respectively, and the plasma cholesterol and triglyceride concentrations were 30% and 28% lower in the HFD-BC group compared with the HFD group. Dietary BC can be the exclusive vitamin A source in mice fed a high-fat diet, as shown by the vitamin A concentration in the plasma and tissues. Feeding BC rather than vitamin A reduces adipose tissue macrophage recruitment markers and plasma lipid concentrations.


Assuntos
Clorofíceas , beta Caroteno , Tecido Adiposo/metabolismo , Animais , Clorofíceas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Expressão Gênica , Fígado , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Triglicerídeos/metabolismo , Vitamina A/farmacologia , beta Caroteno/metabolismo , beta Caroteno/farmacologia
8.
Int J Cosmet Sci ; 44(6): 625-635, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35778881

RESUMO

BACKGROUND: Although retinol skin care products improve the appearance of photoaged skin, there is a need for an effective retinol concentration that provides skin benefits without irritation. OBJECTIVE: To compare the efficacy of topical 0.1%, 0.3% and 1% retinol in remodelling the cutaneous architecture in an in vivo experimental patch test study, and to determine tolerance of the most effective formulations when used in a daily in-use escalation study. METHODS: For the patch test study, retinol products were applied under occlusion, to the extensor forearm of photoaged volunteers (n = 5; age range 66-84 years), and 3 mm skin biopsies obtained after 12 days. Effects of different retinol concentrations, and a vehicle control, on key epidermal and dermal biomarkers of cellular proliferation and dermal remodelling were compared to untreated baseline. Separately, participants (n = 218) recorded their tolerance to 0.3% or 1% retinol over a six-week, approved regimen, which gradually increased the facial applications to once nightly. RESULTS: Retinol treatment induced a stepwise increase in epidermal thickness and induced the expression of stratum corneum proteins, filaggrin and KPRP. 0.3% retinol and 1% retinol were comparably effective at inducing keratinocyte proliferation in the epidermis, whilst reducing e-cadherin expression. Fibrillin-rich microfibril deposition was increased following treatment with 0.3% and 1% retinol (p < 0.01); other dermal components remained unaltered (e.g., fibronectin, collagen fibrils, elastin), and no evidence of local inflammation was detected. The in-use study found that 0.3% retinol was better tolerated than 1% retinol, with fewer and milder adverse events reported (χ2 (1) = 23.97; p < 0.001). CONCLUSIONS: This study suggests that 1% and 0.3% retinol concentrations were similarly effective at remodelling photodamaged skin in an in vivo model of long-term use. Use of 0.3% retinol in the escalation study was associated with fewer adverse reactions when applied daily. Hence, 0.3% retinol may be better tolerated than 1% retinol, thereby allowing longer-term topical application.


CONTEXTE: Même si les produits de soins pour la peau à base de rétinol améliorent l'apparence de la peau photovieillie, il est nécessaire d'obtenir une concentration efficace de rétinol procurant des bénéfices cutanés sans irritation. OBJECTIF: Comparer l'efficacité du rétinol à 0.1%, 0.3% et 1% en application locale dans le remodelage de l'architecture cutanée dans une étude d'irritation cutanée in vivo expérimental, et déterminer la tolérance des formulations les plus efficaces lorsqu'elles sont utilisées dans une étude à doses progressives quotidiennes en cours d'utilisation. MÉTHODES: Pour l'étude d'irritation cutanée, des produits à base de rétinol ont été appliqués sous occlusion, sur le muscle extenseur de l'avant-bras de volontaires présentant des signes de photovieillissement (n = 5; tranche d'âge: 66 à 84 ans), et des biopsies cutanées de 3 mm ont été obtenues après 12 jours. Les effets des différentes concentrations de rétinol, et d'un véhicule témoin sur les principaux biomarqueurs épidermiques et dermiques de la prolifération cellulaire et du remodelage dermique ont été comparés à ceux observés à une région non traitée. Séparément, les participants (n = 218) ont enregistré leur tolérance au rétinol à 0.3% ou 1% au cours d'un schéma posologique approuvé de six semaines, qui a progressivement augmenté les applications faciales à une fois par nuit. RÉSULTATS: Le traitement par rétinol a induit une augmentation progressive de l'épaisseur épidermique, et a induit l'expression des protéines de la couche cornée, la filaggrine et le KPRP. Le rétinol à 0.3% et le rétinol à 1% étaient aussi efficaces pour induire la prolifération des kératinocytes dans l'épiderme, tout en réduisant l'expression de la cadhérine E. Le dépôt de microfibrilles riches en fibrilline a augmenté après un traitement par rétinol à 0.3% et 1% (p < 0.001). CONCLUSIONS: Cette étude suggère que les concentrations de rétinol de 1% et 0.3% étaient aussi efficaces pour remodeler la peau photolésée dans un modèle in vivo lors d'une utilisation à long terme. L'utilisation de rétinol à 0.3% dans l'étude à doses progressives a été associée à moins d'effets indésirables lorsqu'il est appliqué quotidiennement. Par conséquent, le rétinol à 0.3% peut être mieux toléré que le rétinol à 1%, permettant ainsi une application topique à plus long terme.


Assuntos
Envelhecimento da Pele , Vitamina A , Humanos , Idoso , Idoso de 80 Anos ou mais , Vitamina A/farmacologia , Pele , Face , Epiderme
9.
mBio ; 13(4): e0148522, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35862773

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the global pandemic and life-threatening coronavirus disease 2019 (COVID-19). Although vaccines and therapeutic antibodies are available, their efficacy is continuously undermined by rapidly emerging SARS-CoV-2 variants. Here, we found that all-trans retinoic acid (ATRA), a vitamin A (retinol) derivative, showed potent antiviral activity against all SARS-CoV-2 variants in both human cell lines and human organoids of the lower respiratory tract. Mechanistically, ATRA directly binds in a deep hydrophobic pocket of the receptor binding domain (RBD) located on the top of the SARS-CoV-2 spike protein (S) trimer. The bound ATRA mediates strong interactions between the "down" RBDs and locks most of the S trimers in an RBD "all-down" and ACE2-inaccessible inhibitory conformation. In summary, our results reveal the pharmacological biotargets and structural mechanism of ATRA and other retinoids in SARS-CoV-2 infection and suggest that ATRA and its derivatives could be potential hit compounds against a broad spectrum of coronaviruses. IMPORTANCE Retinoids, a group of compounds including vitamin A and its active metabolite all-trans retinoic acid (ATRA), regulate serial physiological activity in multiple organ systems, such as cell growth, differentiation, and apoptosis. The ATRA analogues reported to date include more than 4,000 natural and synthetic molecules that are structurally and/or functionally related to ATRA. Here, we found that ATRA showed potent antiviral activity against all SARS-CoV-2 variants by directly binding in a deep hydrophobic pocket of the receptor binding domain (RBD) located on top of the SARS-CoV-2 spike protein (S) trimer. The bound ATRA mediates strong interactions between the "down" RBDs and locks most of the S trimers in an RBD "all-down" and ACE2-inaccessible inhibitory conformation, suggesting the pharmacological feasibility of using ATRA or its derivatives as a remedy for and prevention of COVID-19 disease.


Assuntos
COVID-19 , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2 , Antivirais/química , Antivirais/farmacologia , COVID-19/tratamento farmacológico , Humanos , Peptidil Dipeptidase A/metabolismo , Ligação Proteica , Glicoproteína da Espícula de Coronavírus/metabolismo , Tretinoína/metabolismo , Tretinoína/farmacologia , Vitamina A/metabolismo , Vitamina A/farmacologia
10.
J Nutr Sci ; 11: e54, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35836697

RESUMO

Maternal obesity may compromise the micronutrient status of the offspring. Vitamin A (VA) is an essential micronutrient during neonatal development. Its active metabolite, retinoic acid (RA), is a key regulator of VA homeostasis, which also regulates adipose tissue (AT) development in obese adults. However, its role on VA status and AT metabolism in neonates was unknown and it was determined in the present study. Pregnant Sprague-Dawley rats were randomised to a normal fat diet (NFD) or a high fat diet (HFD). From postnatal day 5 (P5) to P20, half of the HFD pups received oral RA every 3 d (HFDRA group). NFD pups and the remaining HFD pups (HFD group) received placebo. Six hours after dosing on P8, P14 and P20, n 4 pups per group were euthanised for different measures. It was found that total retinol concentration in neonatal liver and lung was significantly lower in the HFD group than the NFD group, while the concentrations were significantly increased in the HFDRA group. The HFD group exhibited significantly higher body weight (BW) gain, AT mass, serum leptin and adiponectin, and gene expression of these adipokines in white adipose tissue compared with the NFD group; these measures were significantly reduced in the HFDRA group. BAT UCP2 and UCP3 gene expression were significantly higher in pups receiving RA. In conclusion, repeated RA treatment during the suckling period improved the tissue VA status of neonates exposed to maternal obesity. RA also exerted a regulatory effect on neonatal obesity development by reducing BW gain and adiposity and modulating AT metabolism.


Assuntos
Dieta Hiperlipídica , Obesidade Materna , Tecido Adiposo/metabolismo , Animais , Animais Recém-Nascidos , Dieta Hiperlipídica/efeitos adversos , Feminino , Humanos , Micronutrientes , Obesidade/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Tretinoína/metabolismo , Tretinoína/farmacologia , Vitamina A/farmacologia , Aumento de Peso
11.
Sci Rep ; 12(1): 9814, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35697824

RESUMO

There is limited research about the impacts of new nematicides, including fluazaindolizine, fluopyram, and fluensulfone, on the plant-parasitic nematode Meloidogyne incognita, despite it being a pervasive agricultural pest. In this study, M. incognita second-stage juveniles were exposed for 24-h to fluensulfone, fluazaindolizine, fluopyram, and oxamyl and total RNA was extracted and sequenced using next-generation sequencing to determine gene expression. The effects of nematicide exposure on cellular detoxification pathways, common differentially expressed (DE) genes, and fatty acid and retinol-binding genes were examined. Fluopyram and oxamyl had the smallest impacts on the M. incognita transcriptome with 48 and 151 genes that were DE, respectively. These compounds also elicited a weak response in the cellular detoxification pathway and fatty acid and retinol-binding (FAR) genes. Fluensulfone and fluazaindolizine produced robust transcriptional responses with 1208 and 2611 DE genes, respectively. These compounds had strong impacts on cellular detoxification, causing differential regulation of transcription factors and genes in the detox pathway. These compounds strongly down-regulated FAR genes between 52-85%. Having a greater understanding of how these compounds function at a molecular level will help to promote proper stewardship, aid with nematicide discovery, and help to stay a step ahead of nematicide resistance.


Assuntos
Tylenchoidea , Animais , Antinematódeos/farmacologia , Ácidos Graxos/farmacologia , Tylenchoidea/fisiologia , Vitamina A/farmacologia
12.
Meat Sci ; 191: 108847, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35594692

RESUMO

To explore the effects and underlying mechanism of vitamin A on beef marbling fat development, angus steers were injected vitamin A at birth and 1 month of age and in vitro experiments were performed to investigate the effects of retinoic acid (RA) on angiogenesis and adipogenesis of intramuscular stromal vascular (SVF) cells. Results showed that vitamin A administration increased the intramuscular PDGFRα+ adipose progenitors, improved adipogenic potential of intramuscular SVF cells and dramatically upregulated VEGFA. At slaughter, vitamin A increased intramuscular triacylglycerols by 45% without affecting overall fatness. In a 3D culture system, RA promoted capillary sprout development and promoted the subsequent adipogenesis of intramuscular SVF cells by activating VEGFA/VEGFR2 signaling. However, during terminal adipogenesis, RA downregulated PPARγ, C/EBPα and inhibited lipid accumulation. In conclusion, vitamin A/RA upregulate VEGFA and stimulate intramuscular vascular capillary development, which increases intramuscular adipose progenitors and contributes to adipocyte formation. When administrated at neonatal stage, vitamin A promotes beef marbling development without affecting overall fatness.


Assuntos
Músculo Esquelético , Vitamina A , Adipócitos , Adipogenia/fisiologia , Tecido Adiposo , Animais , Bovinos , Tretinoína , Vitamina A/farmacologia
13.
Int J Cosmet Sci ; 44(3): 377-393, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35514037

RESUMO

OBJECTIVE: Skin ageing is a multifactorial process involving formation of reactive oxygen species, consecutive inflammation with reduced epidermal and dermal cell viability and resulting damage to the extracellular matrix. Effective dermocosmetic treatment modalities should ideally address these hallmarks in a holistic approach. Here, we determined the corresponding activity profile of bakuchiol, a plant-derived meroterpene, in an array of in vitro, ex vivo and in vivo studies and compared it to retinol, currently considered as gold standard in topical antiageing cosmetics. METHODS: The antioxidative capacity and power of bakuchiol and retinol were analysed by measuring 2,2'-diphenyl-1-picrylhydrazyl (DPPH) reduction via its absorption decay and electron spin resonance spectroscopy, respectively. Effects on prostaglandin E2 (PGE2), macrophage migration inhibitory factor (MIF), fibroblast growth factor 7 (FGF7), collagen type I and VII (COL1A1, COL7A1), fibronectin (FN) levels as well as the metabolization of water-soluble tetrazolium 1 (WST-1) were determined in human dermal fibroblasts. Epidermal regeneration was assessed utilizing an in vitro wound healing model. FN protein levels were analysed ex vivo after treatment with a formulation containing bakuchiol, retinol or vehicle using suction blister fluid. Skin condition improvement was determined in vivo in a split-face comparison study after application of bakuchiol or vehicle. RESULTS: In contrast to retinol, bakuchiol demonstrated high antioxidative efficacy. Levels of PGE2 and MIF were significantly decreased by both bakuchiol and retinol. Bakuchiol but not retinol significantly increased FGF7 protein levels. WST-1 metabolization levels were significantly augmented by bakuchiol and retinol. Bakuchiol and retinol application led to a significant augmentation of COL1A1, COL7A1 and FN protein levels. Wounds supplemented with bakuchiol but not retinol displayed a significant increase in epidermis regeneration. Clinically, areas treated with a bakuchiol-containing formulation showed a statistically significant increase in FN protein values after a 4-week application compared to untreated areas and areas treated with vehicle. CONCLUSION: These data provide evidence for the multidirectional efficacy of bakuchiol against cellular hallmarks of skin ageing. Its activity profile shares some common features with retinol but demonstrates several hitherto unknown biopositive effects in our studies, namely stimulation of the critical extracellular matrix component FN, and accelerated epidermal regeneration and wound healing.


OBJECTIF: le vieillissement de la peau est un processus multifactoriel impliquant la formation de dérivés réactifs de l'oxygène, une inflammation consécutive qui entraîne une viabilité réduite des cellules du derme et de l'épiderme, et endommage la matrice extracellulaire. Pour être efficaces, les traitements dermocosmétiques devraient dans l'idéal traiter ces caractéristiques selon une approche holistique. Ici, nous avons déterminé le profil d'activité correspondant du bakuchiol, un méroterpène d'origine végétale, dans une série d'études in vitro, ex vivo et in vivo, et l'avons comparé au rétinol, qui est aujourd'hui considéré comme la référence parmi les cosmétiques anti-âge topiques. MÉTHODES: la capacité antioxydante et la puissance du bakuchiol et du rétinol ont été analysées en mesurant la réduction du 2,2-diphényl-1-picrylhydrazyl (DPPH) selon sa décroissance par absorption et à l'aide d'une spectroscopie par résonance magnétique électronique, respectivement. Les effets sur la prostaglandine E2 (PGE2), le facteur inhibiteur de la migration (FIM) des macrophages, le facteur de croissance des fibroblastes 7 (FGF7), le collagène de type I et VII (COL1A1, COL7A1), les taux de fibronectine (FN), ainsi que la métabolisation du tétrazolium 1 soluble dans l'eau (WST-1) ont été déterminés dans des fibroblastes dermiques humains. La régénération épidermique a été évaluée à l'aide d'un modèle de cicatrisation des plaies in vitro. Les taux de fibronectine ont été analysés ex vivo après un traitement avec une formulation contenant du bakuchiol, du rétinol ou un excipient à l'aide d'un liquide d'aspiration sous forme de vésicules. L'amélioration de l'état de la peau a été déterminée in vivo dans une étude de comparaison en hémiface après l'application de bakuchiol ou d'un excipient. RÉSULTATS: Contrairement au rétinol, le bakuchiol s'est avéré présenter une efficacité antioxydante élevée. Les taux de PGE2 et de FIM ont significativement diminué avec le bakuchiol et le rétinol. L'application de bakuchiol s'est accompagnée d'une augmentation significative des taux de protéine FGF7, mais pas celle de rétinol. Les taux de métabolisation du WST-1 ont augmenté de façon significative avec le bakuchiol et le rétinol. L'application de bakuchiol et de rétinol a entraîné une augmentation significative des taux de protéines COL1A1, COL7A1 et fibronectine. Les plaies supplémentées en bakuchiol, mais pas en rétinol, ont montré une augmentation significative de la régénération épidermique. Sur le plan clinique, les zones traitées avec une formulation contenant du bakuchiol ont montré une augmentation statistiquement significative des taux de fibronectine après une application de 4 semaines par rapport aux zones non traitées et aux zones traitées avec un excipient. CONCLUSION: ces données fournissent des preuves de l'efficacité multidirectionnelle du bakuchiol contre les caractéristiques cellulaires du vieillissement de la peau. Son profil d'activité partage certaines caractéristiques communes avec le rétinol, mais démontre plusieurs effets biopositifs jusqu'alors inconnus dans nos études : la stimulation de la fibronectine, composante essentielle de la matrice extracellulaire, et une régénération épidermique et une cicatrisation accélérée des plaies.


Assuntos
Dinoprostona , Envelhecimento da Pele , Colágeno/metabolismo , Colágeno Tipo VII/metabolismo , Colágeno Tipo VII/farmacologia , Dinoprostona/metabolismo , Dinoprostona/farmacologia , Humanos , Fenóis/farmacologia , Pele , Vitamina A/farmacologia
14.
Eur J Pharm Sci ; 174: 106189, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35429602

RESUMO

Targeting hepatic stellate cells (HSCs) can improve the therapeutic efficacy of medicines used to treat hepatic fibrosis. The present work aimed to study the feasibility of homing devices with vitamin A(VA) chemically attached for delivering betulin(Bt)specifically to HSCs. The manufacture and characterisation of VA modified poly (ethylene glycol) -poly (lactide-co-glycolide) block copolymer micelles loaded with Bt (Bt/ VAPPMs) and their potential therapeutic benefits in vitro and in vivo are described in this paper. Bt/VAPPMs were made in a nearly spherical core-shell configuration with diameters under 200nm.In vitro release study showed that Bt/VAPPMs exhibited steady and continuous release for over 168 hours. Bt/VAPPMs had good biocompatibility at the cellular level, according to the safety evaluation, and elicited no inflammatory response in mice. More importantly, as uptake behavior studied in cells and bioimaging experiments in vivo, Bt/VAPPMs exhibited an instinctive liver- targeting capability to focus on activated HSCs. Efficacy tests revealed that administering Bt/VAPPMs effectively inhibits collagen I expression in LX-2 cells in vitro, and this effect was also seen in a mouse model of liver fibrosis. Overall, results demonstrated that Bt/VAPPMs is a promising drug delivery system that possesses specific HSCs targeting ability for treating hepatic fibrosis.


Assuntos
Micelas , Vitamina A , Animais , Células Estreladas do Fígado , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Camundongos , Polímeros/uso terapêutico , Triterpenos , Vitamina A/metabolismo , Vitamina A/farmacologia , Vitamina A/uso terapêutico
15.
Nutrients ; 14(8)2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35458172

RESUMO

The vitamin A metabolite all-trans retinoic acid (RA) plays a key role in tissue homeostasis and mucosal immunity. RA is produced by gut-associated dendritic cells, which are among the first cells encountered by HIV. Acute HIV infection results in rapid reduction of RA levels and dysregulation of immune cell populations whose identities and function are largely controlled by RA. Here, we discuss the potential link between the roles played by RA in shaping intestinal immune responses and the manifestations and pathogenesis of HIV-associated enteropathy and similar conditions observed in SIV-infected non-human primate models. We also present data demonstrating the ability of RA to enhance the activation of replication-competent viral reservoirs from subjects on suppressive anti-retroviral therapy. The data suggest that retinoid supplementation may be a useful adjuvant for countering the pathologic condition of the gastro-intestinal tract associated with HIV infection and as part of a strategy for reactivating viral reservoirs as a means of depleting latent viral infection.


Assuntos
Infecções por HIV , Tretinoína , Animais , Infecções por HIV/tratamento farmacológico , Humanos , Imunidade nas Mucosas , Tretinoína/metabolismo , Tretinoína/farmacologia , Replicação Viral , Vitamina A/farmacologia
16.
ACS Appl Bio Mater ; 5(3): 1120-1129, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35258918

RESUMO

Vitamin A is a fat-soluble compound widely known for vision health. Highly variable reports on its effects on bone health have necessitated further research to truly understand its role on bone cell proliferation. Retinol, one bioactive form of vitamin A, is incorporated into synthetic bone graft scaffolds for low load-bearing clinical bone treatment. The objective of this work is to understand the effects of retinol on osteoblast and osteoclast cells when embedded within calcium phosphate matrices, including interconnected porous 3D printed tricalcium phosphate scaffolds. Results show that hydrophobic retinol can be released from bone scaffolds when a combination of biodegradable polymers, polycaprolactone and polyethylene glycol, are employed as drug carriers. The release of retinol in vitro can support a 20 ± 1% increase in osteoblast (bone-forming) cell proliferation with proper cell adhesion and filopodial extensions. Osteoclast cell morphology is necrosed and torn with a reduction in proliferation at approximately 6 ± 1% when retinol is present. In addition, inhibition of osteoclastic resorption pit bays is noted using scanning electron microscopy. With the scaffolds' round pore interconnectivity facilitating retinol release, this system can provide an alternative to traditional bone grafts while additionally supporting bone healing through enhanced osteoblast cell proliferation and inhibition of osteoclast resorption activity.


Assuntos
Tecidos Suporte , Vitamina A , Fosfatos de Cálcio/farmacologia , Proliferação de Células , Porosidade , Impressão Tridimensional , Tecidos Suporte/química , Vitamina A/farmacologia
17.
Vopr Pitan ; 91(1): 53-64, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35298104

RESUMO

Vitamins are low-molecular compounds consisting of an essential part of the human diet. After entering the human organism vitamins or their precursors can undergo chemical modification, changing their biological properties and regulatory activity. For many decades, vitamins were considered mainly as precursors of enzyme cofactors, and hypovitaminosis was interpreted as a deficiency of a particular metabolite resulting from enzyme's insufficient activity. However, with the development of molecular biology techniques and breakthrough in understanding of gene expression regulation and cell signaling mechanisms, as well as in molecular mechanisms of diseases associated with impaired functions, it became clear that there are significantly more active forms of vitamins, and their functions in the human body are more diverse than it had been suggested previously. The purpose of this review was to consider vitamins' and vitamins' derivatives regulatory and anti-tumor role and their potential for clinical application as main or adjuvant drugs for malignant neoplasms treatment. Material and methods. The present review is based on the results of literature analysis conducted in the Scopus, PubMed, Science Direct databases for the keywords «vitamin A AND cancer¼, «retinoids AND cancer¼, «vitamin D AND cancer¼, «vitamins AND cancer¼, «vitamins AND cancer¼. The search depth was 6 years (2016-2021). Results. Active forms of hydrophilic and lipophilic vitamins are key participants in the processes of chromatin remodeling, genome stability maintaining, covalent modification of proteins, including signaling and regulatory ones, and also act as chemical messengers themselves. Therefore, vitamin deficiency is associated with autoimmune and chronic diseases such as cancer, atherosclerosis, diabetes mellitus, etc. This review considers the regulatory role of active forms of vitamins, their derivatives and vitamin-like substances as well as their involvement in the process of carcinogenesis. Conclusions. Modern studies confirm the high therapeutic potential of vitamins: the use of pharmacological doses of vitamins or their derivatives may help to prevent or fight non-communicable diseases, including cancer.


Assuntos
Deficiência de Vitaminas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Vitamina A/farmacologia , Vitamina D , Vitaminas/farmacologia
18.
Int J Mol Sci ; 23(6)2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35328419

RESUMO

The published literature makes a very strong case that a wide range of disease morbidity associates with and may in part be due to epithelial barrier leak. An equally large body of published literature substantiates that a diverse group of micronutrients can reduce barrier leak across a wide array of epithelial tissue types, stemming from both cell culture as well as animal and human tissue models. Conversely, micronutrient deficiencies can exacerbate both barrier leak and morbidity. Focusing on zinc, Vitamin A and Vitamin D, this review shows that at concentrations above RDA levels but well below toxicity limits, these micronutrients can induce cell- and tissue-specific molecular-level changes in tight junctional complexes (and by other mechanisms) that reduce barrier leak. An opportunity now exists in critical care-but also medical prophylactic and therapeutic care in general-to consider implementation of select micronutrients at elevated dosages as adjuvant therapeutics in a variety of disease management. This consideration is particularly pointed amidst the COVID-19 pandemic.


Assuntos
Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Micronutrientes/metabolismo , Vitamina A/metabolismo , Vitamina D/metabolismo , Zinco/metabolismo , Animais , COVID-19/epidemiologia , COVID-19/metabolismo , COVID-19/virologia , Humanos , Micronutrientes/farmacologia , Pandemias/prevenção & controle , SARS-CoV-2/fisiologia , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Vitamina A/farmacologia , Vitamina D/farmacologia , Vitaminas/metabolismo , Vitaminas/farmacologia , Zinco/farmacologia
19.
Cryo Letters ; 43(1): 10-17, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35315865

RESUMO

BACKGROUND: Vitrification increases the production of reactive oxygen species (ROS) and the antioxidants in the vitrification solution may be beneficial by reducing excessive ROS production. OBJECTIVE: To evaluate the effect of retinol supplementation in vitrification solution on viability, apoptosis and development-related gene expression in vitrified sheep preantral follicles. MATERIALS AND METHODS: Preantral follicles were isolated and randomly assigned into one of five groups: Group1, control fresh preantral follicles; Group 2, vitrification treatment; Group 3, vitrification + 2 µM retinol; Group 4, vitrification + 5 µM retinol; Group 5, vitrification + 10 µM retinol. Preantral follicles were placed in vitrification solutions and then plunged into liquid nitrogen (-196°C). After a week, the follicles were thawed and analyzed for follicular viability by trypan blue exclusion method and for gene expression. RESULTS: Vitrification with 5 µM retinol positively affected viability in comparison with vitrification without retinol (P < 0.05). There was no significant difference in viability among the Group 1, Group 2, Group 3 and Group 5. Expression of apoptotic genes BAX and Casp 3 were higher in the vitrified group, and vitrification with 5 µM retinol (Group 4) is comparable to the control fresh. Expressions of other apoptosis-related genes (i.e., BCL2L1, BAD and BAK) showed significant difference between the control fresh group and the vitrification group with 5 µM retinol. Expression of Annexin5 was also significantly different among various groups. The expression of development competence genes GDF-9 and BMP-15 were higher (P < 0.05) in the Group vitrified with 5 µM retinol. CONCLUSION: The supplementation of 5 µM retinol in vitrification solution was beneficial for the vitrification of ovine preantral follicles.


Assuntos
Vitamina A , Vitrificação , Animais , Apoptose , Criopreservação/métodos , Criopreservação/veterinária , Feminino , Folículo Ovariano , Ovinos , Vitamina A/farmacologia
20.
Int J Cosmet Sci ; 44(2): 201-215, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35238059

RESUMO

OBJECTIVE: Because they limit, even reverse, age-induced skin alterations, retinoids became a staple in cosmetology. However, their use can result in undesired secondary effects and there is a demand for natural sources of compounds with retinoid-like effects. A preliminary screening identified a Harungana madagascariensis plant extract (HME) as possibly inducing genes stimulated by retinol. We analysed its effect on gene and protein expression, comparing it to retinoids. METHODS: Gene expression was analysed by real-time qPCR on RNA from isolated fibroblasts subjected to retinol or the plant extract for 6, 48 or 96 h. Skin markers were quantified in fibroblasts cultured with retinol or extract containing medium, and UV-aged skin explants subjected to topical applications of creams containing retinol, retinaldehyde or HME. RESULTS: Real-time qPCR shows that the extract induced all RARs and RXRs, even RXRγ that was not induced by retinol. Eighty-eight per cent of the 25 early retinoid reaction genes induced by a concentration of retinol are induced by the extract. In fibroblasts, only the extract increased collagen III labelling, while collagen I and fibronectin labelling are increased by retinol and the extract, with higher levels for the extract. When topically applied to UV-aged skin explants, only the cream containing the HME led to increased labelling of CRABP1 in the epidermis. CRABP2 and Ki67 are induced by all three creams and no effect was detected on RXRs. In the dermisthe extract containing cream increased CRABP2, total collagen, procollagen I and collagen I while creams with retinol or retinaldehyde only affected some of these proteins. CONCLUSIONS: The HME induces an overall retinol-like gene induction profile in isolated fibroblasts and retinoid-like stimulation of protein synthesis in both isolated fibroblasts and photoaged skin explants.


OBJECTIFS: Limitant, voire inversant les altérations cutanées induites par l'âge, les rétinoïdes sont devenus incontournables en cosmétologie. Cependant, leur application topique peut entraîner des effets secondaires indésirables et il existe une demande pour des composés naturels ayant des effets similaires à ceux des rétinoïdes. Un screening préliminaire nous avait permis d'identifier un extrait de la plante Harungana madagascariensis (HME) comme pouvant induire des gènes stimulés par le rétinol. Nous avons donc analysé son effet sur l'expression de gènes et de protéines induits par les rétinoïdes et comparé les résultats à ceux obtenus en présence de rétinoïdes. MÉTHODES: L'expression de gènes a été analysée par qPCR en temps réel réalisée sur l'ARN de fibroblastes isolés soumis au rétinol ou à l'extrait végétal pendant 6, 48 ou 96 heures. Différentes protéines cutanées ont été quantifiés dans des fibroblastes cultivés en présence de rétinol ou d'un milieu contenant l'extrait. Des quantifications ont également été faites sur des explants de peau vieillie par les UV et soumis à des applications topiques de crèmes contenant du rétinol, du rétinaldéhyde ou le HME. RESULTATS: La qPCR en temps réel montre que l'extrait induit tous les gènes RARs et RXRs, même RXRγ qui n'était pas induit par le rétinol. Quatre-vingt-huit pour cent des 25 gènes impliqués dans la réaction précoce aux rétinoïdes induits par une concentration de rétinol ont été induits par l'extrait. Dans les fibroblastes, seul l'extrait a augmenté le marquage du collagène III, tandis que le marquage du collagène I et de la fibronectine a été augmenté par le rétinol et l'extrait, avec des niveaux plus élevés pour l'extrait. En application topique sur des explants de peau vieillie par les UV, seule la crème contenant le HME a entraîné une augmentation du marquage de CRABP1 dans l'épiderme. CRABP2 et Ki67 ont été induits par les trois crèmes et aucun effet n'a été détecté sur les RXRs. Dans le derme, la crème contenant l'extrait a augmenté CRABP2, le collagène total, le procollagène I et le collagène I, tandis que les crèmes contenant du rétinol ou du rétinaldéhyde n'ont affecté que certaines de ces protéines. CONCLUSIONS: Chez les fibroblastes isolés, le HME induit un profil d'induction génique globalement similaire à celui du rétinol. Chez les fibroblastes isolés et des explants de peau photo-vieillie, il entraine une stimulation de la synthèse protéique similaire à celle des rétinoïdes.


Assuntos
Retinaldeído , Vitamina A , Idoso , Colágeno/metabolismo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Fibroblastos , Humanos , Extratos Vegetais/farmacologia , Retinaldeído/metabolismo , Retinaldeído/farmacologia , Retinoides/farmacologia , Pele , Regulação para Cima , Vitamina A/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...