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Cosmetic-Medical Treatments
Published in Paloma Tejero, Hernán Pinto, Aesthetic Treatments for the Oncology Patient, 2020
M. Lourdes Mourelle, B. N. Díaz
Vitamin B3 (niacinamide) is perhaps the most studied to treat skin inflammation and erythrosis, calming irritation. The advantages of niacinamide are its anti-inflammatory effects due to inhibition of proinflammatory factors, as well as its ability to increase the expression of serine palmitoyltransferase as the key enzyme for ceramide synthesis [28]. Therefore, studies have been carried out to evaluate the protective effect of cosmetic preparations with 4% niacinamide during radiotherapy, obtaining a significant improvement in symptoms [29].
Role of Vitamin C in Chronic Wound Healing
Published in Qi Chen, Margreet C.M. Vissers, Vitamin C, 2020
Juliet M. Pullar, Margreet C.M. Vissers
Cell culture studies demonstrate that vitamin C can promote the differentiation of keratinocytes, which is critical for reepithelialization in wound healing [93]. In an organotypic culture model, vitamin C enhanced differentiation of rat epidermal keratinocytes, increasing filaggrin expression, a differentiation marker, and the number of keratohyalin granules [94]. It also improved the ultrastructural organization of the stratum corneum, enhancing the characteristic basket-weave pattern of this layer, and promoting extracellular lipid deposition. Finally, vitamin C markedly increased the barrier function of the epidermis, as demonstrated by reductions in transepidermal water loss and permeation rates of corticosterone and mannitol. In support of these findings, others have also shown that vitamin C promotes the synthesis and organization of barrier lipids, increases cornified envelope formation during differentiation, and promotes barrier function [95–99]. More specifically, vitamin C has been shown to enhance ceramide synthesis, which is the major lipid component of the stratum corneum [95,97,99]. It particularly increases formation of ceramides 6 and 7 [95], which are hydroxylated derivatives. The increased synthesis seems to be related to upregulation of ceramide synthetic enzymes including serine palmitoyltransferase and ceramide synthase [97,99].
Micronutrients in the Prevention and Improvement of the Standard Therapy for Alzheimer’s Disease
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
Increased levels of ceramide and its rate-limiting enzyme serine palmitoyltransferase were found in sporadic AD.81,82 Using AD mouse model (TgCRND8), it was demonstrated that the expressions of miR-137, miR-181c, miR-9, and miR-29a/b were downregulated that allowed increased levels of serine palmitoyltransferase and Aβ peptides. Inhibition of this enzyme by L-cycloserine reduced the levels of Aβ peptides and hyperphosphorylated tau protein in the cortex of AD mouse model.81
Identification of a novel SPT inhibitor WXP-003 by docking-based virtual screening and investigation of its anti-fungi effect
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Xin Wang, Xin Yang, Xin Sun, Yi Qian, Mengyao Fan, Zhehao Zhang, Kaiyuan Deng, Zaixiang Lou, Zejun Pei, Jingyu Zhu
Viewed as important structural components of cellular membranes, sphingolipids are a large class of lipids which implicate a wide range of cellular functions in eukaryotic and prokaryotic organisms9–12. Except that, sphingolipids play other multiple roles in fungal cells specifically, such as heat stress response, signal transduction, endocytosis, apoptosis and many others. In particular, it is also one of causes of fungal pathogenesis13–15. Thus, highly concerning on the biology of sphingolipids would be helpful for searching new targets against fungal infection. De novo sphingolipids biosynthesis is a complicated process mediated by a large number of enzymes16. Serine palmitoyltransferase (SPT) is a heterodimeric membrane protein, that could catalyse the formation of 3-ketodihydrosphingosine (3-KDS) from serine and palmitoyl CoA through condensation reaction17. SPT is the initial and rate-limiting enzyme in the de novo biosynthesis of sphingolipids, directly affecting the synthesis of two main groups of sphingolipids in fungal cells, such as inositol phosphoryl ceramide (IPC) and glucosylceramide (GlcCer)11,18–20. Some studies have shown that inhibiting the enzymes involved in the biosynthetic pathways of sphingolipids could decrease the virulence of fungal pathogens21. Especially, SPT inhibitors have been reported that could inhibit the sphingolipid formation effectively, resulting in changes of fungal membranes and cell morphology. Therefore, SPT could be an attractive target against fungal infection13.
Fermented dried Citrus unshiu peel extracts exert anti-inflammatory activities in LPS-induced RAW264.7 macrophages and improve skin moisturizing efficacy in immortalized human HaCaT keratinocytes
Published in Pharmaceutical Biology, 2019
Chulwon Kim, Jun Ji, Seung Ho Baek, Jong Hyun Lee, In Jin Ha, Soon Sung Lim, Hong Jae Yoon, Yun Je Nam, Kwang Seok Ahn
Cells were washed and suspended in Trizol reagent. Total RNA was extracted according to the manufacturer’s instructions (Invitrogen, Life Technologies, Carlsbad, CA, USA). One microgram of total RNA was converted to cDNA by superscript reverse transcriptase and then amplified by a Taq polymerase using reverse transcription polymerase chain reaction (RT-PCR) (TAKARA, Tokyo, Japan). The relative expression of iNOS, COX-2, filaggrin, and SPT were analyzed using PCR with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal control. The following pairs of forward and reverse primer sets were used: iNOS, 5′-TCTTTGACGCTCG-GAACTGTAGCA-3′ and 5′-CGTGAAGCCATGACCTTTCGCATT-3′. COX-2, 5′-TTGCTGTACAAGCAGT-GGCAAAGG-3′ and 5′-AGGACAAACACCGGAGGGAATCTT-3′. Filaggrin, 5′-CAAATCCTGAAGAATCCAGATGAC-3′ and 5′-TGCTTGAGCCAACTTGAATACC-3′, serine-palmitoyltransferase, 5′-TTTCCGGTTTAAAAGTGGTG-3′ and 5′-CTGATGCTTGGAGGAGGAAG-3′. The cDNA reaction was performed at 45 °C for 60 min and 95 °C for 5 min. PCR products were run on 1% agarose gel and then stained with Loading Star (Dynebio, Seongnam, Korea). Stained bands were visualized under UV light and photographed.
Novel ophthalmic formulation of myriocin: implications in retinitis pigmentosa
Published in Drug Delivery, 2019
Chiara Bianca Maria Platania, Michele Dei Cas, Simona Cianciolo, Annamaria Fidilio, Francesca Lazzara, Rita Paroni, Rosario Pignatello, Enrica Strettoi, Riccardo Ghidoni, Filippo Drago, Claudio Bucolo
Myriocin, a natural compound with immunosuppressive activity, worked as a template compound for the development of fingolimod, a drug approved for the treatment of multiple sclerosis. Fingolimod retained the immunosuppressant activity of myriocin but not the inhibitory activity on serine palmitoyltransferase (Zécri, 2016), the enzyme involved in the first step of sphingolipids (i.e. ceramides) synthesis. The dysregulation of ceramide biosynthesis in retinitis pigmentosa (RP), a genetically heterogeneous disorder causing photoreceptor degeneration and blindness, was hypothesized for the first time in 2004. The mutation of ceramide kinase like gene (CERKL) was associated with autosomal recessive RP (RP26) (Tuson et al., 2004). The endogenous substrate of CERKL has not been identified yet. CERKL lipid kinase activity has not been confirmed as well, but the role of CERKL in the regulation of the retinal sphingolipid metabolism was proven by Garanto et al. (2013). The sphingolipid metabolism was found to be altered in the retinal degeneration 10 (rd10) mouse model of RP (Strettoi et al., 2010). Particularly, the levels of pro-apoptotic ceramide were found to be higher in the retina of rd10 mice compared to control mice.