Exudates of Microcystis aeruginosa on oxidative stress and inflammatory responses in gills of Sinocyclocheilus grahami.

Early cyanobacterial blooms studies observed that exposure to blue-green algae led to fish gills impairment. The objective of this work was to evaluate the toxic mechanisms of exudates of Microcystis aeruginosa (MaE) on fish gills. In this study, the toxic mechanism of MaE (2×106 cells/mL) and one of its main components phytosphingosine (PHS) with two concentrations 2.9 ng/mL and 145 ng/mL were conducted by integrating histopathology, biochemical biomarkers, and transcriptomics techniques in Sinocyclocheilus grahami (S. grahami) for 96 h exposure. Damaged gill tissue with epithelial hyperplasia and hypertrophy, remarkable Na+/K+-ATPase (NKA) enzyme activity, disrupted the redox homeostats including lipid peroxidation and inflammatory responses were observed in the fish of MaE exposure group. Compare to MaE exposure, two concentrations of PHS exposure appeared to be a trend of lower degree of tissue damage, NKA activity and oxidative stress, but induced obviously lipid metabolism disorder with higher triglycerides, total cholesterol and total bile acid, which might be responsible for inflammation responses in fish gill. By transcriptome analysis, MaE exposure were primarily enriched in pathways related to gill function and immune response. PHS exposure, with higher number of differentially expressed genes (DEGs), were enriched in Toll-like receptor (TLR), Mitogen-Activated Protein Kinase (MAPK) and NOD-like receptor protein 3 (NLRP3) pathways. We concluded that MaE and PHS were induced the inflammatory responses, with oxidative stress-induced inflammation for MaE exposure but lipid metabolism disorder-induced inflammation for PHS exposure. The present study provided two toxin-induced gill inflammation response pathways under cyanobacterial blooms, which could be a scientific basis for the ecological and health risk assessment in the aquatic environment.

A 'Chiron' approach to novel phytosphingosine mimetics based on a cascade [3,3]-sigmatropic rearrangement.

Straightforward access to enantiomerically pure 3,4-diamino-3,4-dideoxyphytosphingosines, as novel analogues of natural d-ribo-phytosphingosine was accomplished, starting from two available chirons: dimethyl l-tartrate and d-isoascorbic acid. A sequential Overman rearrangement followed by late-stage introduction of the alkyl side chain moiety via olefin cross-metathesis is the cornerstone of this approach. The preliminary evaluation study of the synthesised sphingomimetics, based on their ability to inhibit a proliferation of human cancer cells, showed promising cytotoxicity against Jurkat and HeLa cells for (2R,3R,4S)-2,3,4-triaminooctadecan-1-ol trihydrochloride.

First description of adenosine production by Gnomoniopsis smithogilvyi, causal agent of chestnut brown rot.

Gnomoniopsis smithogilvyi (Gnomoniaceae, Diaporthales) is the main causal agent of chestnut brown rot on sweet chestnut worldwide. The rotting of nuts leads to alterations in the organoleptic qualities and decreased fruit production, resulting in significant economic losses. In 2021, there was an important outbreak of chestnut rot in southern Galicia (Spanish northwest). The profile of secondary metabolites from G. smithogilvyi was studied, especially to determine its capability for producing mycotoxins, as happens with other rotting fungi, due to the possible consequences on the safety of chestnut consumption. Secondary metabolites produced by isolates of G. smithogilvyi growing in potato dextrose agar (PDA) medium were identified using liquid chromatography coupled with high-resolution mass spectrometry. Three metabolites with interesting pharmacological and phyto-toxicological properties were identified based on their exact mass and fragmentation patterns, namely adenosine, oxasetin, and phytosphingosine. The capacity of G. smithogilvyi to produce adenosine in PDA cultures was assessed, finding concentrations ranging from 176 to 834 µg/kg. Similarly, the production of mycotoxins was ruled out, indicating that the consumption of chestnuts with necrotic lesions does not pose a health risk to the consumer in terms of mycotoxins.

Carbon dots combined with phytosphingosine inhibit acid-induced demineralization of hydroxyapatite in vitro.

OBJECTIVES: To study the effects of carbon dots (CDs), in combination with phytosphingosine (PHS), against acid-induced demineralization of hydroxyapatite in vitro. METHODS: CDs were generated from citric acid and urea by microwave heating. Transmission electron microscope (TEM), FT-IR, and fluorescence intensity were used to characterize the CDs. A hydroxyapatite (HAp) model was used to investigate the protective effects of CDs, PHS, and their combinations with and without a salivary pellicle against acid-induced demineralization in vitro. Ca2+ release as a parameter to evaluate the inhibition of demineralization was measured by capillary electrophoresis. The interactions between CDs, PHS, and HAp discs were investigated using a fluorescence detector. RESULTS: Uniform-sized CDs were synthesized, showing typical optical characteristics. CDs exhibited no inhibition of acid-induced demineralization in vitro, in contrast to PHS. Notably, a pre-coating of CDs increased the protective effects of PHS against acid-induced demineralization, which was not disturbed by the presence of a salivary pellicle and Tween 20. Scanning electron microscope (SEM) confirmed the binding and layers formed of both CDs and PHS to the HAp surfaces. Based on fluorescence spectra CDs binding to HAp seemed to be dependent on Ca2+ and PO43- interactions. CONCLUSIONS: CDs combined with PHS showed protective effects against acid-induced demineralization of HAp discs in vitro.

Phytosphingosine inhibits the growth of lung adenocarcinoma cells by inducing G2/M-phase arrest, apoptosis, and mitochondria-dependent pathway cell death in vitro and in vivo.

In order to search for novel antitumor drugs with high efficiency and low toxicity, the anti-lung cancer activity of phytosphingosine was studied. Phytosphingosine is widely distributed in fungi, plants, animals, and has several biological activities, including anti-inflammation and anti-tumor. However, its anti-lung cancer activity needs to be further investigated. The effects and pharmacological mechanisms of phytosphingosine on lung cancer treatment were investigated both in vitro and in vivo. The results showed that phytosphingosine inhibited the growth of lung cancer cell lines. Phytosphingosine induced apoptosis through a mitochondria-mediated pathway, phytosphingosine arrested the cell cycle at the G2/M phase and induced apoptosis in a dose-dependent manner by increasing Bax/Bcl-2 ratio, which caused the decrease of mitochondrial membrane potential to promote the release of cytochrome C, caspase 9 and 3, and degrade PARP in A549 cells. The results showed that phytosphingosine could damage the mitochondrial functions, increase ROS levels, and arrest the cell cycle at the G2/M stages. Finally, phytosphingosine also inhibited the growth of tumor in mice. Taken together, phytosphingosine suppressed the growth of lung cancer cells both in vitro and in vivo and had potential application in the research and development of antitumor drugs. The aim of the present study was to explain the theoretical basis of phytosphingosine therapy for lung cancer and providing new possibilities for lung cancer treatment.

Statistical Study of Low-Intensity Single-Molecule Recognition Events Using DeepTipTM Probes: Application to the Pru p 3-Phytosphingosine System.

The interaction between the plant lipid transfer protein Pru p 3 and phytosphingosine was assessed using an atomic force microscope. Phytosphingosine was covalently immobilized on DeepTipTM probes and Pru p 3 on MicroDeckTM functionalized substrates. Single-molecular interaction events between both molecules were retrieved and classified and the distribution for each one of the identified types was calculated. A success rate of over 70% was found by comparing the number of specific Pru p 3-phytosphingosine interaction events with the total number of recorded curves. The analysis of the distribution established among the various types of curves was further pursued to distinguish between those curves that can mainly be used for assessing the recognition between phytosphingosine (sensor molecule) and Pru p 3 (target molecule) in the context of affinity atomic force microscopy, and those that entail details of the interaction and might be employed in the context of force spectroscopy. The successful application of these functionalized probes and substrates to the characterization of the low-intensity hydrophobic interaction characteristic of this system is a clear indication of the potential of exploiting this approach with an extremely wide range of different biological molecules of interest. The possibility of characterizing molecular assembly events with single-molecule resolution offers an advantageous procedure to plough into the field of molecular biomimetics.

Reticulons bind sphingolipids to activate the endoplasmic reticulum cell cycle checkpoint, the ER surveillance pathway.

The inheritance of a functional endoplasmic reticulum (ER) is ensured by the ER stress surveillance (ERSU) pathway. Here, we made the unexpected discovery that reticulon 1 (Rtn1) and Yop1, well-known ER-curvature-generating proteins, each possess two sphingolipid-binding motifs within their transmembrane domains and that these motifs recognize the ER-stress-induced sphingolipid phytosphingosine (PHS), resulting in an ER inheritance block. Upon binding PHS, Rtn1/Yop1 accumulate on the ER tubule, poised to enter the emerging daughter cell, and cause its misdirection to the bud scars (i.e., previous cell division sites). Amino acid changes in the conserved PHS-binding motifs preclude Rtn1 or Yop1 from binding PHS and diminish their enrichment on the tubular ER, ultimately preventing the ER-stress-induced inheritance block. Conservation of these sphingolipid-binding motifs in human reticulons suggests that sphingolipid binding to Rtn1 and Yop1 represents an evolutionarily conserved mechanism that enables cells to respond to ER stress.

Antimicrobial effect of phytosphingosine in acrylic resin

Abstract This study evaluated color stability (CS), anti-adherence effect (AAE), and cell viability of microorganisms on acrylic resin (AR) surface, treated associated or not with sodium percarbonate (SP). AR specimens were prepared, and color analysis was performed before and after the treatments and the CS was calculated. For analysis of AAE, the samples were sterilized by radiation in a microwave oven. Then samples were randomly distributed: phosphate-buffered saline (PBS - control), 0.5% sodium hypochlorite (SH), phytosphingosine (PHS), and phytosphingosine + SP (PHS+Na2CO3). The specimens remained in contact with solutions for 30 minutes and were later contaminated by Candida albicans. Aliquots were seeded in Petri dishes with Sabouraud Dextrose agar and incubated at 37°C for 24 hours. After the incubation, the number of colonies was counted. The cell viability of adhered microorganisms on the AR was evaluated and 20 fields were observed under an epifluorescence microscope, and the percentage of adhered viable cells was calculated. Data were compared (One-way ANOVA, Tukey, p<.05). As for CS, PHS+ Na2CO3 (0.4±0.1) resulted in less change than PBS (0.9±0.2), similar to the other groups (SH [1.0±0.3)]; PHS [0.9±0.2)]). There was no difference for all tested solutions regarding the ability to avoid microorganism adherence (p>0.05), but PHS (11.2±4.1) resulted in a smaller area of adhered viable cells, statistically different from SH (18.2±7.6) and PBS (26.4±10.8). It was concluded that PHS resulted in lower adhered viable cells and when associated with Na2CO3, also shows a lower effect on the CS of AR.

Resumo Este estudo avaliou estabilidade de cor (EC), efeito antiaderente (EAA) e viabilidade celular de microrganismos em superfície de resina acrílica (RA), tratada com solução de fitoesfingosina, associada ou não ao percarbonato de sódio (PS). Espécimes RA foram preparados e análise de cor foi realizada antes e após os tratamentos e EC foi calculada. Para análise de EAA, as amostras foram esterilizadas por radiação em forno de micro-ondas. Então foram distribuídas aleatoriamente: solução salina tamponada com fosfato (PBS - controle), hipoclorito de sódio 0,5% (SH), fitoesfingosina (PHS) e fitoesfingosina + SP (PHS+Na2CO3). Os espécimes permaneceram em contato com as soluções por 30 minutos e posteriormente foram contaminados por Candida albicans. Alíquotas foram semeadas em placas de Petri com ágar Sabouraud Dextrose e incubadas a 37°C por 24 horas. Após a incubação, o número de colônias foi contado. A viabilidade celular dos microorganismos aderidos na RA foi avaliada e 20 campos foram observados em microscópio de epifluorescência, e a porcentagem de células viáveis aderidas foi calculada. Os dados foram comparados (One-way ANOVA, Tukey, p<0,05). Quanto a EC, o PHS+ Na2CO3 [0,4 (0,1)] resultou em menor alteração que o PBS [0,9 (0,2)], semelhante aos demais grupos (SH [1,0 (0,3)]; PHS [0,9 (0,2)]). Não houve diferença para todas as soluções testadas quanto à capacidade de evitar a aderência de microorganismos (p>0,05), mas o PHS [11,2 (4,1)] resultou em uma área menor de células viáveis aderidas, estatisticamente diferente do SH [18,2 (7,6)] e PBS [26,4 (10,8)]. Concluiu-se que o PHS resultou em menor número de células viáveis aderidas e, quando associado ao Na2CO3, também apresenta menor efeito sobre o EC da RA.

Phytosphingosine alleviates Staphylococcus aureus-induced mastitis by inhibiting inflammatory responses and improving the blood-milk barrier in mice.

Mastitis is one of the common diseases in dairy cows which threatens the health of cows and impacts on economic benefits seriously. Recent studies have been showed that Subacute Ruminal Acidosis (SARA) increased the susceptibility of cow mastitis. SARA leads the disturbance of the rumen microbiota, and the rumen bacterial disordered community is an important endogenous factor of cow mastitis. That is to say, cows which suffer from SARA have a disordered rumen microbiota, a prolonged decline in ruminal PH and a high level of lipopolysaccharide (LPS) in the rumen, blood. Therefore, ruminal metabolism is closely related to the rumen microbiota. However, the specific mechanism of SARA and mastitis still not clear. We found an intestinal metabolite according to the metabonomics, which is correlated to inflammation. Phytophingosine (PS), a product from rumen fluid and milk of the cows which suffer from SARA and mastitis. It has the effect of killing bacteria and anti-inflammatory. Emerging evidences indicate that PS can alleviate inflammatory diseases. However, how PS affects mastitis is largely unknown. In this study, we explored the concrete role of PS on Staphylococcus aureus (S. aureus) -induced mastitis in mice. We found that PS obviously decreased the level of the proinflammatory cytokines. Meanwhile, PS also significantly relieved the mammary gland inflammation caused by S. aureus and restored the function of the blood-milk barrier. Here, we showed that PS increased the expression of the classic Tight-junctions (TJs) proteins including ZO-1, Occludin and Claudin-3. Moreover, PS improves S. aureus-induced mastitis by inhibiting the activation of the NF-κB and NLRP3 signaling pathways. These data indicated that PS relieved S. aureus-induced mastitis effectively. This also provides a reference for exploring the correlation between the intestinal metabolism and inflammation.

[Fermentative production of tetraacetyl phytosphingosine: a review].

Tetraacetyl phytosphingosine (TAPS) is an excellent raw material for natural skin care products. Its deacetylation leads to the production of phytosphingosine, which can be further used for synthesizing the moisturizing skin care product ceramide. For this reason, TAPS is widely used in the skin care oriented cosmetics industry. The unconventional yeast Wickerhamomyces ciferrii is the only known microorganism that can naturally secrete TAPS, and it has become the host for the industrial production of TAPS. This review firstly introduces the discovery, functions of TAPS, and the metabolic pathway for TAPS biosynthesis is further introduced. Subsequently, the strategies for increasing the TAPS yield of W. ciferrii, including haploid screening, mutagenesis breeding and metabolic engineering, are summarized. In addition, the prospects of TAPS biomanufacturing by W. ciferrii are discussed in light of the current progresses, challenges, and trends in this field. Finally, guidelines for engineering W. ciferrii cell factory using synthetic biology tools for TAPS production are also presented.

Divergent access to a novel 3,4-diaminophytosphingosine-like ceramide via sequential Overman rearrangement.

A straightforward approach to a novel phytosphingosine-like ceramide has been accomplished. The cornerstone features of this divergent synthesis are a cascade Overman rearrangement of tris(imidate) to introduce three desired stereogenic centres via sequential chirality transfer and an effective olefin cross-metathesis to install a long side chain. The final unusual phytoceramides were evaluated for their capacity to inhibit the proliferation of cancer cell lines. The preliminary results revealed that compound 21 exhibits promising anticancer activity against HeLa and HCT-116 cells as well as the excellent selectivity in cytotoxicity (malignant vs non-malignant cell lines).

Straightforward access to novel cytotoxic phytosphingosine-like aminotriols from l-erythrose chiron.

A divergent approach to a small library of long-chain 6-amino-1,4,5-triols as novel phytosphingosine-type entities, together with their preliminary cytotoxic evaluation, was achieved. Construction of the target compounds addressed two key aspects. First, the installation of a carbon-nitrogen bond via two prototypes of [3,3]-sigmatropic rearrangements and second the introduction of an alkyl side chain unit by using a late stage olefin cross-metathesis process. As shown in cell viability experiments, the corresponding HCl salts proved to be the most cytotoxic derivatives among all the tested substances, with IC50 values in the lower micromolar range on the Jurkat, HeLa and HCT-116 cell lines.

Micro-Raman spectroscopy analysis of dentin remineralization using eggshell derived nanohydroxyapatite combined with phytosphingosine.

The aim of this study was to assess the remineralization efficacy of chicken eggshell-derived nano-hydroxyapatite (CEnHAp) combined with phytosphingosine (PHS) on artificially induced dentinal lesions. PHS was commercially procured whereas CEnHAp was synthesized using microwave-irradiation method and characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), high-resolution scanning electron microscopy-energy-dispersive X-ray spectroscopy (HRSEM-EDX), and transmission electron microscopy (TEM). A total of 75 pre-demineralized coronal dentin specimens were randomly treated with one of the following test agents (n = 15 each): artificial saliva (AS), casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), CEnHAp, PHS, and CEnHAp-PHS under pH cycling for 7, 14, and 28 days. Vickers microhardness indenter, HRSEM-EDX, and micro-Raman spectroscopy methods were used to assess the mineral changes in the treated dentin samples. Data were submitted to Kruskal-Wallis and Friedman's two-way analyses of variance (p < 0.05). HRSEM and TEM analysis depicted irregular spherical structure of the prepared CEnHAp with a particle size of 20-50 nm. The EDX analysis confirmed the presence of Ca, P, Na and Mg ions. The XRD pattern showed the characteristic crystalline peaks for hydroxyapatite and calcium carbonate that are present in the prepared CEnHAp. Dentin treated with CEnHAp-PHS revealed highest microhardness values along with complete tubular occlusion compared to other groups at all test time intervals (p < 0.05). Specimens treated with CEnHAp showed increased remineralization than those treated with CPP-ACP followed by PHS and AS groups. The intensity of mineral peaks, as observed in the EDX and micro-Raman spectra, confirmed these findings. Further, the molecular conformation of the collagen's polypeptide chains, and amide-I and CH2 peaks attained peak intensities in dentin treated with CEnHAp-PHS and PHS whereas other groups revealed poor stability of collagen bands. Microhardness, surface topography, and micro-Raman spectroscopy analyses revealed that dentin treated with CEnHAp-PHS have an improved collagen structure and stability as well as highest mineralization and crystallinity.

The effect of Phytosphingosine and bioactive glass-ceramics in preventing dental enamel erosion

Abstract This study evaluated the effect of phytosphingosine (PHS) and bioactive glass-ceramic (Biosilicate) on dental enamel in terms of color alteration (ΔE), microhardness, and surface roughness when submitted to erosive challenge (EC). Sixty specimens of bovine teeth (6×6×2mm) were obtained. Initial color (Easyshade, VITA), KHN (HMV-2, Shimadzu), and Ra (SJ-201P, Mitutoyo) measurements were performed. Specimens were separated into groups according to treatments: PHS, 10% Biosilicate, PHS+10% Biosilicate, and artificial saliva (control) and submitted to EC with Coca-Cola for 2 min. This cycle was repeated 4 times daily/15 days. Between cycles, specimens remained in artificial saliva (2 h/37°C). After daily cycles, they were also stored in artificial saliva at 37ºC. Final color, microhardness, and surface roughness measurements were done. Color and KHN data were analyzed by one-way ANOVA, Tukey's test; and Ra, by 2-way ANOVA, repeated measures, and Tukey's test (p<.05). The highest ΔE occurred in Saliva+EC (p<.05). Groups treated with PHS presented lower color change than Saliva+EC (p<.05). All the groups presented mean values above the 50:50% perceptibility (50:50%PT) and acceptability (50:50%AT) thresholds, except for control that showed mean value above 50:50%PT but below 50:50%AT. Biosilicate+EC showed higher relative microhardness than Saliva+EC (p<.05), but was similar to PHS+EC and PHS+Biosilicate+EC. Final enamel surface roughness increased for all the groups (p<.05), except for the control. The Biosilicate may prevent enamel mineral loss induced by erosion better than saliva. The PHS associated or not to Biosilicate demonstrated better color stability than saliva.

Resumo Este estudo avaliou o efeito da Fitoesfingosina (PHS) e da vitrocerâmica bioativa (Biosilicato) sobre o esmalte dental em termos de alteração de cor (ΔE), microdureza (KHN) e rugosidade superficial, quando submetido a desafio erosivo (DE). Sessenta espécimes de dentes bovinos (6×6×2mm) foram obtidos. Foram realizadas leituras de cor inicial (Easyshade, VITA), microdureza (HMV-2, Shimadzu) e rugosidade superfícial (SJ-201P, Mitutoyo). Os espécimes foram separados em grupos de acordo com os tratamentos: PHS, Biosilicato a 10%, PHS+Biosilicato a 10%, e saliva artificial (controle). Em seguida, foram submetidos a DE com Coca-Cola por 2 min. Esse ciclo foi repetido 4 vezes/dia por 15 dias. Entre os ciclos, as amostras foram mantidas em saliva artificial (2 h/37°C). Após os ciclos diários, os espécimes também foram armazenados em saliva artificial a 37ºC. Foram realizadas leituras finais de cor, microdureza e rugosidade superficial. Os dados de cor e microdureza foram analisados ​​por ANOVA de uma via, teste de Tukey; e dados de rugosidade superficial, por ANOVA de duas vias, teste de Tukey (p<.05). A maior ΔE ocorreu em Saliva+DE (p<.05). Grupos tratados com PHS apresentaram menor alteração de cor do que Saliva+DE (p<.05). Biosilicate+DE demonstrou valores intermediários, similar (p>.05) aos outros grupos, exceto Saliva+DE. Todos os grupos presentaram média acima dos limites 50:50% de perceptibilidade (50:50%LP) e aceitabilidade (50:50%LA) exceto o controle que demonstrou média acima do 50:50%LA mas abaixo do 50:50%LP. Biosilicate+DE mostrou maior microdureza realativa do que Saliva+DE (p<.05), mas similar a PHS+DE e PHS+Biosilicato+DE. A rugosidade de superfície do esmalte aumentou para todos os grupos, exceto para o controle que presentou a menor alteração (p<.05). O Biosilicato apode prevenir perda mineral do esmalte indizido pela erosão melhor que a saliva. O PHS associado ou não ao Biosilicato demonstrou melhor estabilidade de cor que a saliva.

The effect of phytosphingosine associated with tooth brushing on color change, surface roughness, and microhardness of dental enamel - an in vitro and in situ study.

OBJECTIVE: This study evaluated the in vitro and in situ effects of phytosphingosine (PHS) associated with tooth brushing on color stability, surface roughness, and microhardness of dental enamel. METHODS: Sixty-four specimens of bovine teeth (6 × 6 × 2 mm) were separated into 8 groups (n = 8): S + TB: PHS (spray) + tooth brushing; TB + S: tooth brushing + PHS (spray); I + TB: PHS (immersion) + tooth brushing; TB + I: tooth brushing + PHS (immersion); TB: tooth brushing; S: PHS spray; I: immersion in PHS solution, and Saliva: immersion in saliva. Tooth brushing simulation (Mavtec, Brazil) was performed (356 rpm on 3.8 cm area by the toothbrush - Soft Tek) for 1, 7, 15, and 30 days. PHS remained in contact with specimens for 15 min. The specimens were evaluated before and after tooth brushing for color alteration (Easy Shade, VITA), and surface roughness (Model SJ-201P Mitutoyo), and Knoop microhardness (HMV-2, Shimadzu Corporation). For the in situ analyses, 8 participants were recruited and received an intraoral device with 6 fragments of bovine enamel (6 × 6 × 2 mm). The properties evaluated were the same as those of the in vitro study. Participants were randomized following best results of in vitro tested protocols, for 15 days: TB, TB + S, I + TB. Data obtained by in vitro (two-way ANOVA, Tukey, p < .05) and in situ (one-way ANOVA, Tukey, p < .05) studies were analyzed. RESULTS: The in vitro study showed that greater color change was found after 30 days. The greatest differences in surface roughness occurred between the initial value and after 1 day. Regarding microhardness, the highest values occurred after 15 and 30 days, which showed similar results. The in situ study showed greater color changes for the TB and I + TB, and greater surface roughness changes for TB as well as a similar increase in microhardness for the PHS protocols, which were higher than TB. CONCLUSIONS: Phytosphingosine leads to an increase in performance regarding color stability, surface roughness, and microhardness when applied. In general, the application of PHS after brushing showed a positive impact on its performance. CLINICAL RELEVANCE: Phytosphingosine proved to be interesting for compound prevention formulations in the dentistry field.

Fermentative production of tetraacetyl phytosphingosine: a review / 生物工程学报

Tetraacetyl phytosphingosine (TAPS) is an excellent raw material for natural skin care products. Its deacetylation leads to the production of phytosphingosine, which can be further used for synthesizing the moisturizing skin care product ceramide. For this reason, TAPS is widely used in the skin care oriented cosmetics industry. The unconventional yeast Wickerhamomyces ciferrii is the only known microorganism that can naturally secrete TAPS, and it has become the host for the industrial production of TAPS. This review firstly introduces the discovery, functions of TAPS, and the metabolic pathway for TAPS biosynthesis is further introduced. Subsequently, the strategies for increasing the TAPS yield of W. ciferrii, including haploid screening, mutagenesis breeding and metabolic engineering, are summarized. In addition, the prospects of TAPS biomanufacturing by W. ciferrii are discussed in light of the current progresses, challenges, and trends in this field. Finally, guidelines for engineering W. ciferrii cell factory using synthetic biology tools for TAPS production are also presented.

O-Cyclic Phytosphingosine-1-Phosphate Protects against Motor Dysfunctions and Glial Cell Mediated Neuroinflammation in the Parkinson's Disease Mouse Models.

O-cyclic phytosphingosine-1-phosphate (cPS1P) is a novel and chemically synthesized sphingosine metabolite derived from phytosphingosine-1-phosphate (S1P). This study was undertaken to unveil the potential neuroprotective effects of cPS1P on two different mouse models of Parkinson's disease (PD). The study used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and neuron specific enolase promoter human alpha-synuclein (NSE-hαSyn) Korl transgenic mice. MPTP was injected for five consecutive days and cPS1P was injected for alternate days for six weeks intraperitoneally. We performed behavioral tests and analyzed the immunohistochemistry and immunofluorescence staining in the substantia nigra pars compacta (SNpc) and the striatum. The behavior tests showed a significant reduction in the motor functions in the PD models, which was reversed with the administration of cPS1P. In addition, both PD-models showed reduced expression of the sphingosine-1-phosphate receptor 1 (S1PR1), and α-Syn which was restored with cPS1P treatment. In addition, administration of cPS1P restored dopamine-related proteins such as tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2), and dopamine transporter (DAT). Lastly, neuroinflammatory related markers such as glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter protein-1 (Iba-1), c-Jun N-terminal kinases (JNK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), tumor necrosis factor-alpha (TNF-α), and interleukin 1 beta (IL-1ß) were all reduced after cPS1P administration. The overall findings supported the notion that cPS1P protects against dopamine depletion, neuroinflammation, and PD-associated symptoms.

Design and evaluation of erucic acid-phytosphingosine structured cationic nanoemulsions as a plasmid DNA delivery system against breast cancer cells.

This study is focused on the preparation and characterization of erucic acid (EA) and phytosphingosine (PS) containing cationic nanoemulsions (NEs) for plasmid DNA (pDNA) delivery. Repurposing of cationic agents guided us to PS, previously used for enhanced interaction with negatively charged surfaces. It was reported that EA might act anti-tumoral on C6 glioma, melanoma, neuroblastoma, and glioblastoma. However, there is only one study about mixed oleic acid-EA liposomes. This gap attracted our interest in the possible synergistic effects of PS and EA on MDA-MB-231 and MCF-7 breast cancer cells. Three cationic NEs (NE 1, NE 2, and NE 3) were prepared and characterized in terms of droplet size (DS), polydispersity index (PDI), and zeta potential (ZP) before and after complexation with pDNA, long-term stability, SDS release, cytotoxicity, and transfection studies. The cationic NEs had DSs of <200 nm, PDIs <0.3, and ZPs > +30 mV. Long-term stability studies revealed that NE 2 and NE 3 were stable. NE 1-pDNA had appropriate particle properties. NE 2 reduced the viability of MDA-MB-231 cells to 11% and of MCF-7 cells to 13% and resulted in the highest number of transfected cells. To sum up, NE 2 containing PS and EA is appropriate for delivering pDNA.

Phytosphingosine induces systemic acquired resistance through activation of sphingosine kinase.

Phytosphingosine (PHS) is a naturally occurring bioactive sphingolipid molecule. Intermediates such as sphingolipid long-chain bases (LCBs) in sphingolipid biosynthesis have been shown to have important roles as signaling molecules. PHS treatment caused rapid cell damage and upregulated the generation of reactive oxygen species (ROS) and ethylene in tobacco plants. These events were followed by the induction of sphingosine kinase (SphK) in a biphasic manner, which metabolized PHS to phytosphingosine-1-phosphate (PHS-1-P). On the other hand, a PHS treatment with a virulent pathogen, Phytophthora parasitica var. nicotianae (Ppn), alleviated the pathogen-induced cell damage and reduced the growth of Ppn. A Ppn infection increased the PHS and PHS-1-P levels significantly in the upper part of the leaves at the infection site at the later stage. In addition, Ppn increased the transcription levels of serine palmitoyltransferase (LCB1 and LCB2) for sphingolipid biosynthesis at the later stage, which was enhanced further by PHS. Moreover, the PHS treatment increased the transcription and activity of SphK, which was accompanied by prominent increases in the transcription levels of ROS-detoxifying enzymes and PR proteins in the later phase of the pathogen infection. Overall, the PHS-induced resistant effects were prominent during the necrotic stage of this hemibiotrophic infection, indicating that it is more beneficial for inhibiting the pathogenicity on necrotic cell death. Phosphorylated LCBs reduced the pathogen-induced cell damage significantly in this stage. These results suggest that the selective channeling of sphingolipids into phosphorylated forms has a pro-survival effect on plant immunity.

The molecular mechanism of phytosphingosine binding to FFAR4/GPR120 differs from that of other fatty acids.

Free fatty acid receptor 4 (FFAR4)/GPR120 comprises a receptor for medium- and long-chain fatty acids. We previously identified phytosphingosine (PHS) as a novel ligand of FFAR4. Although many natural FFAR4 ligands have carboxyl groups, PHS does not, thus suggesting that binding to FFAR4 is driven by a completely different mechanism than other natural ligands such as α-linolenic acid (ALA). To test this hypothesis, we performed docking simulation analysis using a FFAR4 homology model based on a protein model derived from the crystal structure of activated turkey beta-1 adrenoceptor. The docking simulation revealed that the probable hydrogen bonds to FFAR4 differ between various ligands. In particular, binding was predicted between R264 of the FFAR4 and the oxygen of the carboxylate group in ALA, as well as between E249 of the FFAR4 and the oxygen of the hydroxy group at the C4-position in PHS. Alanine substitution at E249 (E249A) dramatically reduced PHS-induced FFAR4 activation but demonstrated a weaker effect on ALA-induced FFAR4 activation. Kinetic analysis and Km values clearly demonstrated that the E249A substitution resulted in reduced affinity for PHS but not for ALA. Additionally, we observed that sphingosine, lacking a hydroxyl group at C4-position, could not activate FFAR4. Our data show that E249 of the FFAR4 receptor is crucial for binding to the hydroxy group at the C4-position in PHS, and this is a completely different molecular mechanism of binding from ALA. Because GPR120 agonists have attracted attention as treatments for type 2 diabetes, our findings may provide new insights into their development.