Essential Lipid Research Articles

Cera-Glow, ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201, improves skin barrier function in clinical study.

Ceramides are essential lipids in stratum corneum for skin permeability barrier function in that they retain the skin moisture and protect from the invasion of foreign pathogens. Previously, we demonstrated that ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201 enhanced ceramide production in human epidermal keratinocytes. Furthermore, for comprehensive knowledge of this effect, in vitro experiments and multi-omics analysis were conducted to explore the underlying mechanisms. This study was designed to identify whether a cosmetic sample (i.e., Cera-Glow) containing the lysates improves the skin barrier function in clinical trials. Twenty-four female participants (45.46 ± 9.78 years) had been enrolled in the transepidermal water loss (TEWL) measurement for 5 days and 21 female participants (50.33 ± 5.74 years) had undergone a skin hydration evaluation for 4 weeks. TEWL and skin hydration were evaluated using a Tewameter and the Epsilon Permittivity Imaging System, respectively. After applying the Cera-Glow sample, all participants recorded a satisfaction survey questionnaire (e.g., satisfaction, efficacy, and adverse reactions). Application of Cera-Glow significantly improved transepidermal water loss induced by 1% (w/v) sodium lauryl sulfate (p < 0.05-0.01) and increased skin hydration (p < 0.01). Metabolic analysis suggested that Cera-Glow should contain beneficial gradients for skin barrier function. According to the questionnaire, most of participants were satisfied with the skin hydration improvement and efficacy of Cera-Glow. Cera-Glow, ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201, can significantly improve skin barrier function.

Quantification of Dolichyl Phosphates Using Phosphate Methylation and Reverse-Phase Liquid Chromatography-High Resolution Mass Spectrometry.

Dolichyl monophosphates (DolPs) are essential lipids in glycosylation pathways that are highly conserved across almost all domains of life. The availability of DolP is critical for all glycosylation processes, as these lipids serve as membrane-anchored building blocks used by various types of glycosyltransferases to generate complex post-translational modifications of proteins and lipids. The analysis of DolP species by reverse-phase liquid chromatography-mass spectrometry (RPLC-MS) remains a challenge due to their very low abundance and wide range of lipophilicities. Until now, a method for the simultaneous qualitative and quantitative assessment of DolP species from biological membranes has been lacking. Here, we describe a novel approach based on simple sample preparation, rapid and efficient trimethylsilyl diazomethane-dependent phosphate methylation, and RPLC-MS analysis for quantification of DolP species with different isoprene chain lengths. We used this workflow to selectively quantify DolP species from lipid extracts derived of Saccharomyces cerevisiae, HeLa, and human skin fibroblasts from steroid 5-α-reductase 3- congenital disorders of glycosylation (SRD5A3-CDG) patients and healthy controls. Integration of this workflow with global lipidomics analyses will be a powerful tool to expand our understanding of the role of DolPs in pathophysiological alterations of metabolic pathways downstream of HMG-CoA reductase, associated with CDGs, hypercholesterolemia, neurodegeneration, and cancer.

Lavender Essential Oil Modulates Hepatic Cholesterol Metabolism in HepG2 Cells.

Cholesterol is an essential lipid that guarantees several biological processes in eukaryotic cells. Its metabolism is regulated by a complex protein network that could be significantly influenced by numerous exogenous sources, such as essential oils (EOs). For instance, it has been speculated that monoterpenoid and sesquiterpenoid compounds contained in lavender essential oil (LEO) may exert important hypocholesterolemic activities. However, the molecular mechanisms by which LEO influences cholesterol homeostasis are not characterized. In this work, we evaluated the ability of LEO to regulate the protein network that controls cholesterol metabolism in the HepG2 cell line. The main findings indicate that LEO administration increases intracellular cholesterol content. Concurrently, LEO affects the expression of proteins involved in cholesterol uptake, biosynthesis, and trafficking. These effects are partially mediated by terpinene-4-ol, one of the most abundant compounds in LEO. These results demonstrate that LEO modulates cholesterol metabolism in hepatic cells.

Mass spectrometry imaging reveals the spatial distribution of essential lipids in Daphnia magna – potential implications for trophic ecology

ABSTRACT Lipids and fatty acids are key dietary components for the nutrition of organisms at all trophic levels. They are required to build cellular structures such as cell membranes, serve as energy storage, and take part in signal transduction cascades. For decades, ecological research investigated how dietary fatty acid availability contributes to the fitness of individuals and their populations. The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is of particular interest because its dietary availability determines the fitness of many aquatic consumers. Because of the small body size of zooplankton, only bulk tissue fatty acid analysis was previously performed, and thus the tissue-specific importance of EPA for zooplankton remained elusive. We used matrix-assisted laser desorption/ionization–mass spectrometry imaging (MALDI-MSI) to reveal the tissue-specific distribution of functional phospholipids in the herbivorous zooplankton Daphnia magna. We demonstrate several lipid species for heart, egg, gut, gonad, somatic, and neurological tissues of D. magna, including the compound eye as well as the optical and cerebral ganglion. The compound eye revealed a large diversity in lipid species containing EPA, which were also found in other neurological tissues and eggs. Such knowledge of tissue-specific fatty acid requirements is essential to investigate how selective allocation of dietary fatty acids within this key grazer affects processes on a functional and molecular level from the individual to food web scales. This methodological advancement will facilitate investigations on how invertebrate physiology and behaviour adjust to changing environmental conditions and potentially affect food web structures, including the trophic transfer of dietary fatty acids.

Physiological level of LDL cholesterol and lipoprotein metabolism with apoprotein B100. An update for the clinician

Teleologically (physiological end or purpose), LP-apoB100 are macromolecules whose biological objective is to package in the liver within very-low-density lipoproteins (VLDL) (density 0.96-1.006 g/L), essential hydrophobic lipids, especially triglycerides (TG) and esterified cholesterol. Once assembled, the hepatocyte secretes VLDL into the systemic circulation; this way, essential hydrophobic lipids (insoluble in water) can be transported from the liver to peripheral tissues in an aqueous medium such as plasma. In the systemic circulation and influenced by the energy balance, VLDL (by hydrolysis of its triglycerides), fulfill its primary physiological purpose, releasing glycerol and especially fatty acids (FA) towards the cardiac and skeletal muscle tissues. Which, in turn, will be used as an energy substrate for beta-oxidation and adenosine triphosphate (ATP) generation or towards the adipose tissue to be used as a substrate for the resynthesis of triglycerides (adipocyte lipogenesis) and its eventual rehydrolysis with the release of fatty acids (adipocyte lipolysis).

The content of nutrients and biogenic elements in enriched artemia salina

The work is devoted to the development of technology for enriching artemia with biologically active substances. The development of technology for enriching artemia with biologically active substances is important as an opportunity to obtain starter feeds for aquaculture with the desired properties. High content of high-grade protein, vitamins, amino acids, fatty acids, biogenic elements is of great importance. During artificial cultivation of artemia in a closed cycle in the conditions of aquaculture, there is a problem of sufficient accumulation of substances in its body that provide high nutritional and biological value. To solve this problem, we have developed a technology for enriching artemia with biologically active substances at the nauplium stage. The enrichment of artemia with vitamins, amino acids, probiotics, adaptogens, essential lipids allows us to create a new generation of bio-feeds containing a living symbiotic microbiota and ingredients capable of forming balanced complex of functional nutrition for fish. The aim of the study was to evaluate the biological and energy value, the content of proteins, fats, carbohydrates, moisture, ash, micro- and macroelements, heavy metals in artemia at different stages of ontogenesis against the background of its enrichment with a complex of biologically active substances. Intact and enriched cysts, intact and enriched decapsulated artemia eggs, enriched artemia nauplii were analyzed. It was found that against the background of enrichment with biologically active substances, the indicators of metabolic energy increased, the mass fraction of crude protein, the mass fraction of fat and the content of minerals and biogenic elements increased.

Integrated multi-omics and machine learning approach reveals lipid metabolic biomarkers and signaling in age-related meibomian gland dysfunction

Meibomian gland dysfunction (MGD) is a prevalent inflammatory disorder of the ocular surface that significantly impacts patients’ vision and quality of life. The underlying mechanism of aging and MGD remains largely uncharacterized. The aim of this work is to investigate lipid metabolic alterations in age-related MGD (ARMGD) through integrated proteomics, lipidomics and machine learning (ML) approach. For this purpose, we collected samples of female mouse meibomian glands (MGs) dissected from eyelids at age two months (n = 9) and two years (n = 9) for proteomic and lipidomic profilings using the liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. To further identify ARMGD-related lipid biomarkers, ML model was established using the least absolute shrinkage and selection operator (LASSO) algorithm. For proteomic profiling, 375 differentially expressed proteins were detected. Functional analyses indicated the leading role of cholesterol biosynthesis in the aging process of MGs. Several proteins were proposed as potential biomarkers, including lanosterol synthase (Lss), 24-dehydrocholesterol reductase (Dhcr24), and farnesyl diphosphate farnesyl transferase 1 (Fdft1). Concomitantly, lipidomic analysis unveiled 47 lipid species that were differentially expressed and clustered into four classes. The most notable age-related alterations involved a decline in cholesteryl esters (ChE) levels and an increase in triradylglycerols (TG) levels, accompanied by significant differences in their lipid unsaturation patterns. Through ML construction, it was confirmed that ChE(26:0), ChE(26:1), and ChE(30:1) represent the most promising diagnostic molecules. The present study identified essential proteins, lipids, and signaling pathways in age-related MGD (ARMGD), providing a reference landscape to facilitate novel strategies for the disease transformation.

Transferrin, insulin, and progesterone modulate intracellular concentrations of coenzyme Q and cholesterol, products of the mevalonate pathway, in undifferentiated PC12 cells.

Coenzyme Q (CoQ) is important not only as an essential lipid for the mitochondrial electron transport system, but also as an antioxidant. CoQ levels decrease during aging and in various diseases. Orally administered CoQ is not readily taken up in the brain, so it is necessary to develop a method to increase the amount of CoQ in neurons. CoQ is synthesized via mevalonate pathway, like cholesterol. Transferrin, insulin, and progesterone are factors used in the culture of neurons. In this study, we determined the effect of these reagents on cellular CoQ and cholesterol levels. The administration of transferrin, insulin, and progesterone increased cellular CoQ levels in undifferentiated PC12 cells. When serum was removed and only insulin was administered, intracellular CoQ levels increased. This increase was even more pronounced with concurrent administration of transferrin, insulin, and progesterone. Cholesterol level decreased by the administration of transferrin, insulin, and progesterone. Progesterone treatment lowered intracellular cholesterol levels in a concentration-dependent manner. Our findings suggest that transferrin, insulin, and progesterone may be useful in regulating CoQ levels and cholesterol levels, which are products of the mevalonate pathway.

Endocytosis of LXRs: Signaling in liver and disease.

Nuclear receptors are among one of the major transcriptional factors that induces gene regulation in the nucleus. Liver X receptor (LXR) is a transcription factor which regulates essential lipid homeostasis in the body including fatty acid, cholesterol and phospholipid synthesis. Liver X receptor-retinoid X receptor (LXR-RXR) heterodimer is activated by either of the ligand binding on LXR or RXR. The promoter region of the gene which is targeted by LXR is bound to the response element of LXR. The activators bind to the heterodimer once the corepressor is dissociated. The cellular process such as endocytosis aids in intracellular trafficking and endosomal formation in transportation of molecules for essential signaling within the cell. LXR isotypes play a crucial role in maintaining lipid homeostasis by regulating the level of cholesterol. In the liver, the deficiency of LXRα can alter the normal physiological conditions depicting the symptoms of various cardiovascular and liver diseases. LXR can degrade low density lipoprotein receptors (LDLR) by the signaling of LXR-IDOL through endocytic trafficking in lipoprotein uptake. Various gene expressions associated with cholesterol level and lipid synthesis are regulated by LXR transcription factor. With its known diversified ligand binding, LXR is capable of regulating expression of various specific genes responsible for the progression of autoimmune diseases. The agonists and antagonists of LXR stand to be an important factor in transcription of the ABC family, essential for high density lipoprotein (HDL) formation. Endocytosis and signaling mechanism of the LXR family is broad and complex despite their involvement in cellular growth and proliferation. Here in this chapter, we aimed to emphasize the master regulation of LXR activation, regulators, and their implications in various metabolic activities especially in lipid homeostasis. Furthermore, we also briefed the significant role of LXR endocytosis in T cell immune regulation and a variety of human diseases including cardiovascular and neuroadaptive.

Evaluation of Antimalarial Activity of Ethanolic Extract of Annona muricata L.: An in vivo and an in silico Approach.

In Nigeria, Annona muricata L. has been used to treat a variety of ailments. The mechanism of the antimalarial activity of ethanolic leaf extract of Annona muricata (EEAML) was investigated using both an in vivo and an in silico approach. The experimental mice were divided into five groups: A-F. The mice in groups B-F were inoculated with Plasmodium berghei NK-65 and treated accordingly. Groups A and B are the negative and positive controls (infected and untreated), respectively. Group C received 10 mg/kg chloroquine (standard drug), whereas groups D-F received 100, 200, and 300 mg/kg body weight of the extract orally respectively. The mice were euthanized eight days after infection, and their liver and blood were collected and used in biochemical tests. Molecular docking was performed using the extract's HPLC compounds and Plasmodium falciparum proteins. In the suppressive, prophylactic, and curative tests, there was a significant decrease (p < 0.05) in parasitemia levels in groups treated with the extract compared to the positive control and standard drug. When compared to the positive control, there was a significant (p < 0.05) reduction in liver MDA, total cholesterol, and total triglyceride levels. The binding energies of luteolin and apigenin-pfprotein complexes were significantly (p < 0.05) higher compared to their respective references. The anti-plasmodial activity of the extract may result from its hypolipidemic effect, which deprives the parasite of essential lipid molecules needed for parasite growth, as well as from the inhibitory effects of apigenin and luteolin on specific proteins required for the Plasmodium metabolic pathway.

Association of apolipoprotein ε4 allele with intellectual disability in children with cerebral palsy

Background: The apolipoprotein E (ApoE) protein is the most essential lipid transporter in the brain which is vital in neurodevelopment. The production of ApoE is regulated by several genes and increases under certain conditions such as cerebral injury. This study was carried out to assess the association between APOE alleles on intellectual disability (ID) and assess their relationship with cerebral palsy (CP) in south Indian children. Materials and Methods: The participants (n = 45) were children aged 1–15 years of age, who were diagnosed with CP and presenting with speech or hearing impairment. All patients were of South Indian descent. Family history, medical history, clinical investigations, and cognitive abilities of the patients were recorded. Exome sequencing of the APOE gene was performed. Results: APOE ε4 allele was detected in 9/45 (P = 0.002) CP patients. Both carriers and noncarriers of the ε4 allele had mild-, moderate-, severe-, and profound intellectual disabilities. Conclusion: The role of APOE ε4 as a possible biomarker in cognition decline in CP is still questionable, but the ε4 allele as a potential risk factor for developing Alzheimer's disease is strongly relevant. Further studies are warranted to study the association of the APOE ε4 allele in CP and ID.

Metabolic depletion of sphingolipids inhibits agonist-induced endocytosis of the serotonin1A receptor.

G protein-coupled receptors (GPCRs) are vital cellular signaling machinery and currently represent ~40% drug targets. Endocytosis of GPCRs is an important process that allows stringent spatiotemporal control over receptor population on the cell surface. Although the role of proteins in GPCR endocytosis is well addressed, the contribution of membrane lipids in this process is rather unexplored. Sphingolipids are essential functional lipids in higher eukaryotes and are implicated in several neurological functions. To understand the role of sphingolipids in GPCR endocytosis, we subjected cells expressing human serotonin1A receptors (an important neurotransmitter GPCR involved in cognitive and behavioral functions) to metabolic sphingolipid depletion using fumonisin B1 , an inhibitor of sphingolipid biosynthetic pathway. Our results, using flow cytometric analysis and confocal microscopic imaging, show that sphingolipid depletion inhibits agonist-induced endocytosis of the serotonin1A receptor in a concentration-dependent manner, which was restored when sphingolipid levels were replenished. We further show that there was no change in the internalization of transferrin, a marker for clathrin-mediated endocytosis, under sphingolipid-depleted condition, highlighting the specific requirement of sphingolipids for endocytosis of serotonin1A receptors. Our results reveal the regulatory role of sphingolipids in GPCR endocytosis and highlight the importance of neurotransmitter receptor trafficking in health and disease.

MATHEMATICAL MODELING OF THE EXTRACTION PROCESS IN THE ACOUSTIC EXTRACTOR

One of the most promising physical methods of extraction processes intensification is ultrasound. Dissemination of sound waves in the device occurs by periodic rarefaction and compression of the liquid with the corresponding frequency to the frequency of sound wave oscillations and with a rarefaction amplitude equal to the compression amplitude. Effects of mixing and heating of the liquid, pulsation, collapse of cavitation bubbles is occurred during the operation of the ultrasonic generator. Extraction under the ultrasound influence has its advantages. The equipment has the possibility of continuous operation and is suitable for mass extraction of medicinal products from plants; the extraction time is reduced; the process takes place at a low temperature, which is very important for the thermolabile pharmaceutical ingredients. Sound waves are mechanical vibrations in solids, liquids, and gases that have frequencies higher than 20 kHz. Sound waves moves in any matter, they are associated with cycles of compression and expansion during movement in the medium, in contrast with electromagnetic waves. It is possible to reduce the extraction operating temperature of thermolabile compounds using ultrasound. In addition, any solvent can be used during ultrasonic extraction. Ultrasonic extraction can be used to extract biologically active substances such as essential oils, lipids, and dietary supplements from plants. To calculate the process of extraction of biologically active substances in an acoustic extractor, it is necessary to develop a mathematical model for establishing diffusion coefficients and extraction time.

Mycobacterial mycolic acids trigger inhibitory receptor Clec12A to suppress host immune responses

Mycobacteria often cause chronic infection. To establish persistence in the host, mycobacteria need to evade host immune responses. However, the molecular mechanisms underlying the evasion strategy are not fully understood. Here, we demonstrate that mycobacterial cell wall lipids trigger an inhibitory receptor to suppress host immune responses. Mycolic acids are major cell wall components and are essential for survival of mycobacteria. By screening inhibitory receptors that react with mycobacterial lipids, we found that mycolic acids from various mycobacterial species bind to mouse Clec12A, and more potently to human Clec12A. Clec12A is a conserved inhibitory C-type lectin receptor containing immunoreceptor tyrosine-based inhibitory motif (ITIM). Innate immune responses, such as MCP-1 production, and PPD-specific recall T cell responses were augmented in Clec12A-deficient mice after infection. In contrast, human Clec12A transgenic mice were susceptible to infection with M. tuberculosis. These results suggest that mycobacteria dampen host immune responses by hijacking an inhibitory host receptor through their specific and essential lipids, mycolic acids. The blockade of this interaction might provide a therapeutic option for the treatment or prevention of mycobacterial infection.

Effect of drying methods on the nutrient content, protein and lipid quality of edible insects from East Africa

This study investigated the effect of different drying methods on nutrient composition and quality of three edible insects from East Africa.Ruspolia differens (grasshopper),Gryllus bimaculatus (cricket) andBunea alcinoe (caterpillar) were freeze dried, oven dried, sun dried, direct solar cabinet dried, boiled before sun dried or direct solar cabinet dried. Proximate composition, available lysine, and protein digestibility were not significantly affected by drying methods. The protein digestibility corrected amino acid score was lower in boiled dried cricket and caterpillar than the other dried forms. Boiled and dried insects had lowest proportions of linoleate and α-linolenate. Despite these losses in boiled dried insects, the essential amino acid scores and lipid quality indices of differently dried insects were within desirable limits for human nutrition. Sun drying and solar cabinet drying on their own or with prior boiling could be cost-effective and affordable alternatives to freeze drying and oven drying for preserving edible insects.

Pathogenic role of 25-hydroxycholesterol in cancer development and progression.

Cholesterol is an essential lipid that serves several important functions, including maintaining the homeostasis of cells, acting as a precursor to bile acid and steroid hormones and preserving the stability of membrane lipid rafts. 25-hydroxycholesterol (25-HC) is a cholesterol derivative that may be formed from cholesterol. 25-HC is a crucial component in various biological activities, including cholesterol metabolism. In recent years, growing evidence has shown that 25-HC performs a critical function in the etiology of cancer, infectious diseases and autoimmune disorders. This review will summarize the latest findings regarding 25-HC, including its biogenesis, immunomodulatory properties and role in innate/adaptive immunity, inflammation and the development of various types of cancer.

An update on the nutritional profiles of quinoa (Chenopodium quinoa Willd.), amaranth (Amaranthus spp.), and chia (Salvia hispanica L.), three key species with the potential to contribute to food security worldwide

AbstractOne of the major challenges facing the world nowadays is to ensure enough access to healthy food for a growing population. Under this food scenario, it should be noted that increasing food production is as important as improving its nutritional quality. Thus, different agronomy research and innovation programs have pursued food security through the increase in the quantity and nutritional quality of plant‐based foods. One key aspect in this respect is to increase agrobiodiversity by expanding the cultivation of underutilized highly nutritious crops such as chia, quinoa, or amaranth. The outstanding nutritional value of these crops resides in the compositional characteristics of their seeds, which include the presence of significant levels (and a good balance) of proteins, essential amino acids, lipids, and other components such as phenols, minerals, fiber, or vitamins, all contributing to support nutritious diets that also has health benefits such as the prevention of cardiovascular diseases. All of them, chia, amaranth, and quinoa, are considered emerging crops outside their center of origin (which is mainly located in South America), and their cultivation has been expanded worldwide in the last decade. This review mainly highlights recent knowledge about the nutritional characteristics of these three Latin American crops, with the aim of providing an updated information regarding the compositional profiles of their seeds.

ADMET-Evaluation, Pharmacokinetics, Drug-likeness and Medicinal Chemistry of GCMS Identified Bioactive Compounds of Moringa oleifera Natural-Ripened-Dried Methanolic Pod Extract (MOMPE) as a Potential Source of Natural Drug Frontrunner for Next Generation

Over centuries, Moringa oleifera has been used as an integral part of Ayurveda, Siddha and Unani systems of medicine, besides this miracle tree has a wide range of nutritional and bioactive compounds, including proteins, essential amino acids, carbohydrates, lipids, fiber, vitamins, minerals, phenolic compounds, phytosterols and others. The miracle tree is endowed with a wide range of pharmacological properties, including anti-diabetic, anti-inflammatory, anti-carcinogenic, antioxidant, cardioprotective, antimicrobial and hepatoprotective activities. However, deeper dimensions of authentic data on plant based natural products in relation to drug discovery, pharmacokinetics properties of biomolecules is far lacking. ADMET prospecting is eventually expected to contribute to success of MO based lead candidates in drug design, development program besides saving time and money. This study is the first of its kind reporting summative ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicology) properties of all bioactive compounds Moringa oleifera methanolic pod extract (MOMPE) as a potential source of natural drug lead using Swiss ADME. A total of 12 compounds namely - 7-Octadecyne, 2-methyl- (C19H36); 3,7,11,15-Tetramethyl-2-hexadecen-1-ol (C20H40O); 3,7,11,15-Tetramethyl-2-hexadecen-1-ol (C20H40O); 6,9,12,15-Docosatetraenoic acid, me (C23H38O2); Cyclohexanol, 5-methyl-2-(1-methylethyl)- (C10H20O); 3,7,11,15-Tetramethyl-2-hexadecen-1-ol (C20H40O); Palmitic acid vinyl ester (C18H34O2); .γ.-Tocopherol (C28H48O2); Vitamin E (C29H50O2); Cholesta-7,9(11)-dien-3-ol, 4,4-dim (C29H48O); γ.-Sitosterol (C29H50O); Stigmasta-5,24(28)-dien-3-ol, (3.β.,24Z)- (C29H48O). Most of the MOPBNPs are non-substrate for both P-gp (P-glycoprotein) and CYP (Cytochrome P-450 isoenzymes). All the compounds were evaluated for properties viz., GI absorption, BBB permeant, Pgp substrate, CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4 inhibitors, Lipinski, Ghose, Veber, Egan, Muegge, rule and Bioavailability Score to provide baseline information on PBNPs in MONRD pod.&#x0D; Keywords: PBNPs; NGDDT; ADMET; Moringa oleifera; Secondary Metabolites MONRD pod

Negative Effects of Cyanotoxins and Adaptative Responses of Daphnia.

The plethora of cyanobacterial toxins are an enormous threat to whole ecosystems and humans. Due to eutrophication and increases in lake temperatures from global warming, changes in the distribution of cyanobacterial toxins and selection of few highly toxic species/ strains are likely. Globally, one of the most important grazers that controls cyanobacterial blooms is Daphnia, a freshwater model organism in ecology and (eco)toxicology. Daphnia-cyanobacteria interactions have been studied extensively, often focusing on the interference of filamentous cyanobacteria with Daphnia's filtering apparatus, or on different nutritional constraints (the lack of essential amino acids or lipids) and grazer toxicity. For a long time, this toxicity only referred to microcystins. Currently, the focus shifts toward other deleterious cyanotoxins. Still, less than 10% of the total scientific output deals with cyanotoxins that are not microcystins; although these other cyanotoxins can occur just as frequently and at similar concentrations as microcystins in surface water. This review discusses the effects of different cyanobacterial toxins (hepatotoxins, digestive inhibitors, neurotoxins, and cytotoxins) on Daphnia and provides an elaborate and up-to-date overview of specific responses and adaptations of Daphnia. Furthermore, scenarios of what we can expect for the future of Daphnia-cyanobacteria interactions are described by comprising anthropogenic threats that might further increase toxin stress in Daphnia.

Ablation of sphingosine kinase 2 suppresses fatty liver-associated hepatocellular carcinoma via downregulation of ceramide transfer protein

Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer, the third leading cause of cancer-associated death worldwide. With the increasing prevalence of metabolic conditions, non-alcoholic fatty liver disease (NAFLD) is emerging as the fastest-growing HCC risk factor, and it imposes an additional layer of difficulty in HCC management. Dysregulated hepatic lipids are generally believed to constitute a deleterious environment cultivating the development of NAFLD-associated HCC. However, exactly which lipids or lipid regulators drive this process remains elusive. We report herein that sphingosine kinase 2 (SphK2), a key sphingolipid metabolic enzyme, plays a critical role in NAFLD-associated HCC. Ablation of Sphk2 suppressed HCC development in NAFLD livers via inhibition of hepatocyte proliferation both in vivo and in vitro. Mechanistically, SphK2 deficiency led to downregulation of ceramide transfer protein (CERT) that, in turn, decreased the ratio of pro-cancer sphingomyelin (SM) to anti-cancer ceramide. Overexpression of CERT restored hepatocyte proliferation, colony growth and cell cycle progression. In conclusion, the current study demonstrates that SphK2 is an essential lipid regulator in NAFLD-associated HCC, providing experimental evidence to support clinical trials of SphK2 inhibitors as systemic therapies against HCC.