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![diagram showing parts of the ceramide synthesis pathway. Ceramides are synthesised de novo via the combination of a sphingoid base, generated by the condensation of l-serine and an acyl-CoA, with an acyl chain, via the action of ceramide synthase enzymes. The dihydroceramide formed can be converted to different ceramide classes via the action of dihydroceramide desaturases. Ceramides can be reversibly converted to sphingomyelins (CER[NS/AS]) or glucosylceramides via the main hydrolysis pathways. Alterations in the de novo and hydrolysis pathways can alter the levels of ceramides measured. 3-KDR 3-ketodihydrosphingosine reductase, AH alpha-hydroxyceramide with 6-hydroxysphingone base, AP alpha-hydroxyceramide with phytosphingosine base, AS alpha-hydroxyceramide with sphingosine base, CERS ceramide synthases, DEGS1 dihydroceramide desaturase 1, DEGS2 dihydroceramide desaturase 2, EODS ester-linked omega hydroxy dihydroceramide, EOH ester-linked omega hydroxy 6-hydroxyceramide, EOP ester-linked omega hydroxy phytoceramide, EOS ester-linked omega hydroxyceramide, GCase glucosylceramidase, GCS glucosylceramide synthase, NH non-hydroxyceramide with 6-hydroxysphingone base, NP non-hydroxyceramide with phytosphingosine base, NS non-hydroxyceramide with sphingosine base, SMase sphingomyelinase, SMS sphingomyelin synthase, SPT serine palmitoyltransferase, ? as-yet unidentified desaturase enzyme.](publication/366312218/figure/fig1/AS:11431281107619117@1671163206125/diagram-showing-parts-of-the-ceramide-synthesis-pathway-Ceramides-are-synthesised-de.png)
diagram showing parts of the ceramide synthesis pathway. Ceramides are synthesised de novo via the combination of a sphingoid base, generated by the condensation of l-serine and an acyl-CoA, with an acyl chain, via the action of ceramide synthase enzymes. The dihydroceramide formed can be converted to different ceramide classes via the action of dihydroceramide desaturases. Ceramides can be reversibly converted to sphingomyelins (CER[NS/AS]) or glucosylceramides via the main hydrolysis pathways. Alterations in the de novo and hydrolysis pathways can alter the levels of ceramides measured. 3-KDR 3-ketodihydrosphingosine reductase, AH alpha-hydroxyceramide with 6-hydroxysphingone base, AP alpha-hydroxyceramide with phytosphingosine base, AS alpha-hydroxyceramide with sphingosine base, CERS ceramide synthases, DEGS1 dihydroceramide desaturase 1, DEGS2 dihydroceramide desaturase 2, EODS ester-linked omega hydroxy dihydroceramide, EOH ester-linked omega hydroxy 6-hydroxyceramide, EOP ester-linked omega hydroxy phytoceramide, EOS ester-linked omega hydroxyceramide, GCase glucosylceramidase, GCS glucosylceramide synthase, NH non-hydroxyceramide with 6-hydroxysphingone base, NP non-hydroxyceramide with phytosphingosine base, NS non-hydroxyceramide with sphingosine base, SMase sphingomyelinase, SMS sphingomyelin synthase, SPT serine palmitoyltransferase, ? as-yet unidentified desaturase enzyme.
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The menopause can lead to epidermal changes that are alleviated by hormone replacement therapy (HRT). We hypothesise that these changes could relate to altered ceramide production, and that oestrogen may have a role in keratinocyte ceramide metabolism. White Caucasian women were recruited into three groups: pre-menopausal (n = 7), post-menopausal (...
Citations
... Bilateral ovariectomy in mice resulted in reduced skin barrier function, decreased skin recovery after acute disruption, increased irritant contact dermatitis [78], and downregulated epidermal proteins, filaggrin and involucrin [79]. Furthermore, post-menopausal stratum corneum contained lower ceramide levels, whereas estradiol treatment enhanced ceramides [80]. Overall, estrogen may improve skin barrier homeostasis [78,81], while progesterone seems to impair skin barrier homeostasis and delay recovery [82][83][84]. ...
Vesicular hand eczema (VHE), a clinical subtype of hand eczema (HE), showed limited responsiveness to alitretinoin, the only approved systemic treatment for severe chronic HE. This emphasizes the need for alternative treatment approaches. Therefore, our study aimed to identify drug repurposing opportunities for VHE using transcriptomics and genomics data. We constructed a gene network by combining 52 differentially expressed genes (DEGs) from a VHE transcriptomics study with 3 quantitative trait locus (QTL) genes associated with HE. Through network analysis, clustering, and functional enrichment analyses, we investigated the underlying biological mechanisms of this network. Next, we leveraged drug–gene interactions and retrieved pharmaco-transcriptomics data from the DrugBank database to identify drug repurposing opportunities for (V)HE. We developed a drug ranking system, primarily based on efficacy, safety, and practical and pricing factors, to select the most promising drug repurposing candidates. Our results revealed that the (V)HE network comprised 78 genes that yielded several biological pathways underlying the disease. The drug–gene interaction search together with pharmaco-transcriptomics lookups revealed 123 unique drug repurposing opportunities. Based on our drug ranking system, our study identified the most promising drug repurposing opportunities (e.g., vitamin D analogues, retinoids, and immunomodulating drugs) that might be effective in treating (V)HE.
... In addition, there is also diversity in the chain lengths of the fatty acids and sphingosine bases. Most ceramides in the stratum corneum are non-hydroxy acyl sphingosine (NS) (carbon chain length: [16][17][18][19][20][21][22][23][24] [41][42][43]. The ceramide chain length is important to the stratum corneum structure and ceramide abundance, and short ceramide chains lead to a loss in barrier function [41,[44][45][46]. ...
... Most ceramides in the stratum corneum are non-hydroxy acyl sphingosine (NS) (carbon chain length: [16][17][18][19][20][21][22][23][24] [41][42][43]. The ceramide chain length is important to the stratum corneum structure and ceramide abundance, and short ceramide chains lead to a loss in barrier function [41,[44][45][46]. Amide-linked fatty acids (carbon chain length and saturation) and heterogenous ceramides with appropriate ratios are also necessary for a vital barrier. ...
Psoriasis is a long-lasting skin condition characterized by redness and thick silver scales on the skin’s surface. It involves various skin cells, including keratinocytes, dendritic cells, T lymphocytes, and neutrophils. The treatments for psoriasis range from topical to systemic therapies, but they only alleviate the symptoms and do not provide a fundamental cure. Moreover, systemic treatments have the disadvantage of suppressing the entire body’s immune system. Therefore, a new treatment strategy with minimal impact on the immune system is required. Recent studies have shown that sphingolipid metabolites, particularly ceramide and sphingosine-1-phosphate (S1P), play a significant role in psoriasis. Specific S1P–S1P-receptor (S1PR) signaling pathways have been identified as crucial to psoriasis inflammation. Based on these findings, S1PR modulators have been investigated and have been found to improve psoriasis inflammation. This review will discuss the metabolic pathways of sphingolipids, the individual functions of these metabolites, and their potential as a new therapeutic approach to psoriasis.
... In addition, the treatment of primary human keratinocytes with estradiol (10 nM) led to an increase in the formation of ceramides, which suggests that oestrogen plays a direct regulatory role in the metabolism of keratinocyte ceramides. 45 Another in vitro study conducted with human cancer cells that expressed oestrogen receptors showed that a considerable reduction in ceramide buildup could be achieved through incubation with estradiol. 44 Taken together, these findings show that ageing is linked to levels of circulating ceramide, which, in postmenopausal women, appear to be regulated by levels of estradiol. ...
Introduction:
Insulin resistance (IR) is one of the common chronic metabolic disorders in Africa and elsewhere. Accumulation of lipids in the body may be due to an imbalance in the metabolism of lipids, glucose and proteins. Ceramides are a sphingolipid class of lipids that are biologically active and vital in the production of more complex lipids. Circulating ceramides are thought to have a role in the development of obesity-related IR, although the precise involvement remains unclear.
Aim:
To investigate the impact of circulating ceramide on IR and body adiposity in people with and without type 2 diabetes mellitus (T2DM).
Methodology:
The study was observational and cross-sectional. There were a total of 84 volunteers with T2DM and 75 nondiabetics (control). The participants' ages, body mass indexes (BMI), waist circumferences, and blood pressure (BP) were among the clinical parameters assessed. Ceramide levels, fasting plasma glucose (FPG), lipids, basal insulin levels and glycated haemoglobin (HbA1c) were also measured. Additionally, the homeostatic model assessment for IR (HOMA-IR) and beta cell function (HOMA-β) were computed.
Results:
T2DM and control participants had different mean values for anthropometric parameters, BP, FPG, HbA1c, lipids, insulin, HOMA-IR, HOMA-β and ceramide levels (p < .05 for all). HOMA-IR, HOMA-β and cardiovascular risk were significant correlates with ceramide levels in the T2DM group (r = 0.24; -0.34; 0.24, p < .05, respectively). Further, FPG (OR = 1.83, p = .01) and ceramide (OR = 1.05, p = .01) levels were significant predictors of IR in the case group.
Conclusion:
Patients with T2DM exhibited high ceramide concentrations, which, when combined with high FPG, were associated with IR. The consequences of circulating ceramides in health and disease; however, merit further research.
... It has been proven that the polyunsaturated cell membrane phospholipids are safeguarded by vitamin E. This effect was shown on the repair function of the human epithelium in the skin and other parts of the body [53]. Both vitamin E and estrogens are important in building of collagen, membrane functioning and metabolism of the cells [54,55]. Accordingly influence of vitamin E on menopausal atrophic changes of vaginal epithelium is very probable. ...
Menopause is a physiological change in any woman. Nevertheless, its symptoms could be difficult to accept, and hormone therapy can be sometimes unattractive or contraindicated. Vitamin E components are phytoestrogens, so they are believed to be useful in some indications including menopause. This review aimed to assess the available evidence on the effectiveness of vitamin E in alleviating menopausal symptoms. The Pubmed/MEDLINE, Cochrane Library and Scopus databases were screened. All types of studies that assessed the effectiveness of vitamin E in alleviating menopausal symptoms were included. The PICO question was: “How does vitamin E supplementation affect menopausal symptom occurrence?” The PROSPERO ID number of this review is CRD42022328830. After quality assessment, 16 studies were included in the analysis. The studies were divided into three groups in which the influence of vitamin E on the genital syndrome of menopause, vasomotor symptoms and vascular and metabolic changes were assessed. Vitamin E influences postmenopausal hot flashes, vascular modulation, plasma lipid profile level and vaginal changes. Compared to vitamin E, estrogen administration leads to better clinical effects. Nevertheless, vitamin E might serve as additive to hormone therapy and its alternative in women with contraindications to estrogens. More quality data are necessary to draw final conclusions.
Serotonin (5-HT) is a vital modulatory neurotransmitter responsible for regulating most behaviors in the brain. An inefficient 5-HT synaptic function is often linked to various mental disorders. Primarily, membrane proteins controlling the expression and activity of 5-HT synthesis, storage, release, receptor activation, and inactivation are critical to 5-HT signaling in synaptic and extra-synaptic sites. Moreover, these signals represent information transmission across membranes. Although the lipid membrane environment is often viewed as fairly stable, emerging research suggests significant functional lipid–protein interactions with many synaptic 5-HT proteins. These protein–lipid interactions extend to almost all the primary lipid classes that form the plasma membrane. Collectively, these lipid classes and lipid–protein interactions affect 5-HT synaptic efficacy at the synapse. The highly dynamic lipid composition of synaptic membranes suggests that these lipids and their interactions with proteins may contribute to the plasticity of the 5-HT synapse. Therefore, this broader protein–lipid model of the 5-HT synapse necessitates a reconsideration of 5-HT’s role in various associated mental disorders.
Background
Aging, menopause, and seasonal changes alter the lipid composition of the outermost skin layer, the stratum corneum, resulting in dry and itchy skin.
Aims
This clinical trial aimed at evaluating the effects of a wheat polar lipid complex (WPLC) on skin characteristics in women showing dry and wrinkled skin, investigating its effects in a subgroup of postmenopausal women, and assessing if benefits were maintained after supplementation.
Methods
Seventy‐two women with dry and wrinkled skin were recruited in this double‐blind, randomized, parallel‐group study, and allocated to three groups of 24 subjects, each including at least 10 postmenopausal women. For 56 days, subjects consumed the WPLC supplement (oil or powder), or the placebo. Skin hydration, transepidermal water loss (TEWL), elasticity, and profilometry were evaluated at baseline, after 14, 28, and 56 days of supplementation, and 56 days after the end of supplementation. Additionally, a lipidomic analysis was performed to examine changes in superficial skin layers over 56 days.
Results
Dietary supplementation with WPLC rapidly improved all parameters. It increased skin hydration, smoothness, and elasticity while decreasing TEWL, roughness, and wrinkle depth after only 14 days of supplementation. These effects were also observed in the subpopulation of postmenopausal women and led to an improved self‐perception of skin. For all the parameters, outcomes were not maintained after the supplementation was stopped. The lipidomic analysis revealed 10 compounds evolving over the 56 days of WPLC supplementation.
Conclusion
WPLC supplementation improved skin hydration, smoothness, elasticity, and wrinkledness within 14 days and, as expected, did not last after supplementation was stopped.
Background: Neuropathic and venous leg ulcers are chronic wounds associated with devitalized tissue and recurrent infection. Management should be guided by accurate tissue assessment, including the use of planimetry, which provides tissue types as a percentage of the total wound bed surface area.
Objective: This innovative study aimed to assess and identify the wound bed tissues, as a percentage, of neuropathic and venous ulcers using digital planimetry, providing support to nurses optimize the management of necrotic tissues and, consequently, to avoid wound infection.
Methods: This cross-sectional study enrolled 24 patients with chronic wounds who were assessed from January to March 2021 at the Wound Outpatients Clinic. The wound photographs were analyzed using Image J 1.53e and a smartphone with WoundDoc Plus® 2.8.2 via digital planimetry. Statistical analyses
were performed using the binomial test, t-test, and Mann-Whitney.
Results: Median wound areas (p=0.3263) did not differ between the group with 2 or 3 risk factors for delayed healing (Md: 31.7) and the group with up to 1 risk factor (Md: 5.3). A low exudate level was associated with the up-to-1-risk-factor-for-delayed-healing group (p=0.0405), while a medium level was associated with the two-or-three-risk-factor group (p=0.0247). A heat map displayed the tissue percentages in the wound bed. In the group with 2 or 3 risk factors for delayed healing, 91.7% (11/12) had less
than 70% granulation tissue, which was the primary factor for this group (p<0.0001). Additionally, 66.7% (8/12) of patients with 2 or 3 risk factors for delayed healing exhibited discolored and/or dark red granulation tissue as the primary factor (p=0.0130).
Conclusion: This novel identification of wound area and tissue types as a percentage, using digital planimetry, can play a crucial role in assisting nurses in decision-making related to the appropriate management of devitalized tissues. Furthermore, this measurements may facilitate the conducting of virtual wound consultations and offer valuable support in the development of protocols aimed at preventing infection and biofilm formation in the wound bed.
