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The roles of ceramides and multivesicular emulsion (MVE) technology in atopic dermatitis: a narrative review

Chng CC

Med J Malaysia, 2024 Jan;79(1):85-94.
PMID: 38287763

INTRODUCTION: Atopic dermatitis (AD) is a highly prevalent chronic inflammatory skin condition. In Malaysia, a prevalence of 13.4% was reported for children between one and six years of age, one of the highest prevalence rates of AD in Asia. Many guidelines recommended moisturisers as the mainstay of treatment strategy for AD. Selecting an effective and suitable moisturiser for people with AD plays a crucial role in avoiding acute exacerbation of AD and achieving remission.
MATERIALS AND METHODS: Given that an array of active ingredients and topical vehicles for moisturisers are available in the market, this review summarised the roles of ceramides and multivesicular emulsion (MVE) technology in managing AD to help guide treatment decisions.
RESULTS: Ceramides are essential in maintaining the skin permeability barrier and hydration, modulating skin immunity through anti-inflammatory and antimicrobial defence system, and regulating cellular functions. Low levels and altered structures and composition of ceramides, compromised skin permeability barrier and increased transepidermal water loss were commonly observed in AD patients. Most clinical studies have shown that ceramidedominant moisturisers are safe and effective in adults and children with AD. MVE technology offers an attractive delivery system to replenish ceramides in the SC, repairing the compromised skin permeability barrier and potentially improving patient compliance.
CONCLUSION: Recommending clinically proven therapeutic moisturisers with the right ingredients (level, ratio, structure and composition), alongside an effective sustained release delivery system, to AD patients is one key strategy to successful disease control and flare prevention, subsequently reducing the disease burden to patients, families and societies.

Matched MeSH terms: Ceramides/therapeutic use
Molecular targets of endothelial phosphatidic acid regulating major depressive disorder

Edwards MJ, Wilson GC, Keitsch S, Soddemann M, Wilker B, Müller CP, et al.

J Neurochem, 2022 Nov;163(4):357-369.
PMID: 36227646 DOI: 10.1111/jnc.15708

Major depressive disorder (MDD) is a severe disease of unknown pathogenesis with a lifetime prevalence of ~10%. Therapy requires prolonged treatment that often fails. We have previously demonstrated that ceramide levels in the blood plasma of patients and in mice with experimental MDD are increased. Neutralization of blood plasma ceramide prevented experimental MDD in mice. Mechanistically, we demonstrated that blood plasma ceramide accumulated in endothelial cells of the hippocampus, inhibited phospholipase D (PLD) and thereby decreased phosphatidic acid in the hippocampus. Here, we demonstrate that phosphatidic acid binds to and controls the activity of phosphotyrosine phosphatase (PTP1B) in the hippocampus and thus determines tyrosine phosphorylation of a variety of cellular proteins including TrkB. Injection of PLD, phosphatidic acid, or inhibition of PTP1B abrogated MDD and normalized cellular tyrosine phosphorylation, including phosphorylation of TrkB and neurogenesis in the hippocampus. Most importantly, these treatments also rapidly normalized behavior of mice with experimental MDD. Since phosphatidic acid binds to and inhibits PTP1B, the lack of phosphatidic acid results in increased activity of PTP1B and thereby in reduced tyrosine phosphorylation of TrkB and other cellular proteins. Thus, our data indicate a novel pathogenetic mechanism of and a rapidly acting targeted treatment for MDD.

Matched MeSH terms: Ceramides
Sex-specific pleiotropic changes in emotional behavior and alcohol consumption in human α-synuclein A53T transgenic mice during early adulthood

Kalinichenko LS, Kohl Z, Mühle C, Hassan Z, Hahn A, Schmitt EM, et al.

J Neurochem, 2024 Mar;168(3):269-287.
PMID: 38284431 DOI: 10.1111/jnc.16051

Point mutations in the α-synuclein coding gene may lead to the development of Parkinson's disease (PD). PD is often accompanied by other psychiatric conditions, such as anxiety, depression, and drug use disorders, which typically emerge in adulthood. Some of these point mutations, such as SNCA and A30T, have been linked to behavioral effects that are not commonly associated with PD, especially regarding alcohol consumption patterns. In this study, we investigated whether the familial PD point mutation A53T is associated with changes in alcohol consumption behavior and emotional states at ages not yet characterized by α-synuclein accumulation. The affective and alcohol-drinking phenotypes remained unaltered in female PDGF-hA53T-synuclein-transgenic (A53T) mice during both early and late adulthood. Brain region-specific activation of ceramide-producing enzymes, acid sphingomyelinase (ASM), and neutral sphingomyelinase (NSM), known for their neuroprotective properties, was observed during early adulthood but not in late adulthood. In males, the A53T mutation was linked to a reduction in alcohol consumption in both early and late adulthood. However, male A53T mice displayed increased anxiety- and depression-like behaviors during both early and late adulthood. Enhanced ASM activity in the dorsal mesencephalon and ventral hippocampus may potentially contribute to these adverse behavioral effects of the mutation in males during late adulthood. In summary, the A53T gene mutation was associated with diverse changes in emotional states and alcohol consumption behavior long before the onset of PD, and these effects varied by sex. These alterations in behavior may be linked to changes in brain ceramide metabolism.

Matched MeSH terms: Ceramides
Fulltext Patient acceptability, efficacy, and skin biophysiology of a cream and cleanser containing lipid complex with shea butter extract versus a ceramide product for eczema

Hon KL, Tsang YC, Pong NH, Lee VW, Luk NM, Chow CM, et al.

Hong Kong Med J, 2015 Oct;21(5):417-25.
PMID: 26314567 DOI: 10.12809/hkmj144472

To investigate patient acceptability, efficacy, and skin biophysiological effects of a cream/cleanser combination for childhood atopic dermatitis.

Matched MeSH terms: Ceramides/pharmacology; Ceramides/therapeutic use*
Gut Microbial Ecosystem in Parkinson Disease: New Clinicobiological Insights from Multi-Omics

Tan AH, Chong CW, Lim SY, Yap IKS, Teh CSJ, Loke MF, et al.

Ann Neurol, 2021 03;89(3):546-559.
PMID: 33274480 DOI: 10.1002/ana.25982

OBJECTIVE: Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, and their clinical relevance.
METHODS: Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry.
RESULTS: Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR-based metabolome. Microbiome and NMR-based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls included bioactive molecules with putative neuroprotective effects (eg, short chain fatty acids [SCFAs], ubiquinones, and salicylate) and other compounds increasingly implicated in neurodegeneration (eg, ceramides, sphingosine, and trimethylamine N-oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability-gait disorder scores.
INTERPRETATION: Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut-brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021;89:546-559.

Matched MeSH terms: Ceramides/metabolism