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Effect of PEGylated lipid and Lecinol S-10 on physico-chemical properties and encapsulation efficiency of palmitoleate-palmitoleic acid vesicles

Teo YY, Misran M, Low KH

J Liposome Res, 2014 Sep;24(3):241-8.
PMID: 24597523 DOI: 10.3109/08982104.2014.891234

A vesicle is a microscopic particle composed of a lipid bilayer membrane that separates the inner aqueous compartment from the outer aqueous environment. Palmitoleate-palmitoleic acid vesicles were prepared and their physico-chemical properties were investigated. Moreover, mixed vesicles composed of palmitoleic acid and PEGylated lipid and/or a mixture of phospholipids were also prepared. The stabilizing effects of these double-chain lipids on the formation of palmitoleate-palmitoleic acid vesicles were studied. Stability of the vesicle suspension was examined using particle size and zeta potential at 30 °C. The magnitude of the zeta potential was relatively lower in the vesicle suspension with the presence of phospholipid. Although some of the mixed vesicles that were formed were not very stable, they displayed potential for encapsulating the active ingredient calcein and the encapsulation efficiencies of calcein were encouraging. The palmitoleate-palmitoleic acid-DPPE-PEG2000 vesicle showed the most promising stability and encapsulation efficiency.

Matched MeSH terms: Phosphatidylinositols/chemistry
Fulltext Roles of phosphatidylinositol-3-kinases signaling pathway in inflammation-related cancer: Impact of rs10889677 variant and buparlisib in colitis-associated cancer

Razali NN, Raja Ali RA, Muhammad Nawawi KN, Yahaya A, Mohd Rathi ND, Mokhtar NM

World J Gastroenterol, 2023 Oct 28;29(40):5543-5556.
PMID: 37970476 DOI: 10.3748/wjg.v29.i40.5543

BACKGROUND: Phosphatidylinositol-3-kinases (PI3K) is a well-known route in inflammation-related cancer. Recent discovery on PI3K-related genes revealed a potential variant that links ulcerative colitis (UC) and colorectal cancer (CRC) with colitis-associated cancer (CAC). PI3K/AKT pathway has been recommended as a potential additional therapeutic option for CRC due to its substantial role in modifying cellular processes. Buparlisib is a pan-class I PI3K inhibitor previously shown to reduce tumor growth.
AIM: To investigate the regulation of rs10889677 and the role of buparlisib in the PI3K signaling pathway in CAC pathogenesis.
METHODS: Genomic DNA from 32 colonic samples, including CAC (n = 7), UC (n = 10) and CRC (n = 15), was sequenced for the rs10889677 mutation. The mutant and wildtype fragments were amplified and cloned in the pmirGLO vector. The luciferase activity of cloned vectors was assessed after transfection into the HT29 cell line. CAC mice were induced by a mixture of a single azoxymethane injection and three cycles of dextran sulphate sodium, then buparlisib was administered after 14 d. The excised colon was subjected to immunohistochemistry for Ki67 and Cleaved-caspase-3 markers and quantitative real-time polymerase chain reaction analysis for Pdk1 and Sgk2.
RESULTS: Luciferase activity decreased by 2.07-fold in the rs10889677 mutant, confirming the hypothesis that the variant disrupted miRNA binding sites, which led to an increase in IL23R expression and the activation of the PI3K signaling pathway. Furthermore, CAC-induced mice had a significantly higher disease activity index (P < 0.05). Buparlisib treatment significantly decreased mean weight loss in CAC-induced mice (P < 0.05), reduced the percentage of proliferating cells by 5%, and increased the number of apoptotic cells. The treatment also caused a downward trend of Pdk1 expression and significantly decreased Sgk2 expression.
CONCLUSION: Our findings suggested that the rs10889677 variant as a critical initiator of the PI3K signaling pathway, and buparlisib had the ability to prevent PI3K-non-AKT activation in the pathophysiology of CAC.

Matched MeSH terms: Phosphatidylinositols/adverse effects
Monashia flava gen. nov., sp. nov., an actinobacterium of the family Intrasporangiaceae

Azman AS, Zainal N, Mutalib NA, Yin WF, Chan KG, Lee LH

Int J Syst Evol Microbiol, 2016 Feb;66(2):554-561.
PMID: 26556816 DOI: 10.1099/ijsem.0.000753

A novel actinobacterial strain, MUSC 78T, was isolated from a mangrove soil collected from Peninsular Malaysia. The taxonomic status of this strain was determined using a polyphasic approach. Comparative 16S rRNA gene sequence analysis revealed that strain MUSC 78T represented a novel lineage within the class Actinobacteria. Strain MUSC 78T formed a distinct clade in the family Intrasporangiaceae and was related most closely to members of the genera Terrabacter (98.3-96.8 % 16S rRNA gene sequence similarity), Intrasporangium (98.2-96.8 %), Humibacillus (97.2 %), Janibacter (97.0-95.3 %), Terracoccus (96.8 %), Kribbia (96.6 %), Phycicoccus (96.2-94.7 %), Knoellia (96.1-94.8 %), Tetrasphaera (96.0-94.9 %) and Lapillicoccus (95.9 %). Cells were irregular rod-shaped or cocci and stained Gram-positive. The cell-wall peptidoglycan type was A3γ, with ll-diaminopimelic acid as the diagnostic diamino acid. The main cell-wall sugar was mannose and lower amounts of galactose and rhamnose were present. The predominant menaquinone was MK-8(H4). The polar lipid profile consisted of phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, diphosphatidylglycerol and phosphoglycolipid. The predominant fatty acids were iso-C15 : 0, anteiso-C15 : 0 and iso-C16 : 0. The DNA G+C content was 73.1 mol%. Based on this polyphasic study, MUSC 78T exhibited phylogenetic and phenotypic differences from members of the genera of the family Intrasporangiaceae, and therefore a novel species of a new genus, Monashia flava gen. nov., sp. nov., is proposed. The type strain of Monashia flava is MUSC 78T ( = DSM 29621T = MCCC 1K00454T = NBRC 110749T).

Matched MeSH terms: Phosphatidylinositols
Interaction of monomeric Ebola VP40 protein with a plasma membrane: A coarse-grained molecular dynamics (CGMD) simulation study

Mohamad Yusoff MA, Abdul Hamid AA, Mohammad Bunori N, Abd Halim KB

J Mol Graph Model, 2018 Jun;82:137-144.
PMID: 29730487 DOI: 10.1016/j.jmgm.2018.04.010

Ebola virus is a lipid-enveloped filamentous virus that affects human and non-human primates and consists of several types of protein: nucleoprotein, VP30, VP35, L protein, VP40, VP24, and transmembrane glycoprotein. Among the Ebola virus proteins, its matrix protein VP40 is abundantly expressed during infection and plays a number of critical roles in oligomerization, budding and egress from the host cell. VP40 exists predominantly as a monomer at the inner leaflet of the plasma membrane, and has been suggested to interact with negatively charged lipids such as phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylserine (PS) via its cationic patch. The hydrophobic loop at the C-terminal domain has also been shown to be important in the interaction between the VP40 and the membrane. However, details of the molecular mechanisms underpinning their interactions are not fully understood. This study aimed at investigating the effects of mutation in the cationic patch and hydrophobic loop on the interaction between the VP40 monomer and the plasma membrane using coarse-grained molecular dynamics simulation (CGMD). Our simulations revealed that the interaction between VP40 and the plasma membrane is mediated by the cationic patch residues. This led to the clustering of PIP2 around the protein in the inner leaflet as a result of interactions between some cationic residues including R52, K127, K221, K224, K225, K256, K270, K274, K275 and K279 and PIP2 lipids via electrostatic interactions. Mutation of the cationic patch or hydrophobic loop amino acids caused the protein to bind at the inner leaflet of the plasma membrane in a different orientation, where no significant clustering of PIP2 was observed around the mutated protein. This study provides basic understanding of the interaction of the VP40 monomer and its mutants with the plasma membrane.

Matched MeSH terms: Phosphatidylinositols
Gonadal microRNA Expression Profiles and Their Potential Role in Sex Differentiation and Gonadal Maturation of Mud Crab Scylla paramamosain

Waiho K, Fazhan H, Zhang Y, Zhang Y, Li S, Zheng H, et al.

Mar Biotechnol (NY), 2019 Jun;21(3):320-334.
PMID: 30835008 DOI: 10.1007/s10126-019-09882-1

Although the sexual dimorphism in terms of gonadal development and gametogenesis of mud crab has been described, the internal regulating mechanism and sex differentiation process remain unclear. A comparative gonadal miRNA transcriptomic study was conducted to identify miRNAs that are differentially expressed between testes and ovaries, and potentially uncover miRNAs that might be involved in sex differentiation and gonadal maturation mechanisms of mud crabs (Scylla paramamosain). A total of 10 known miRNAs and 130 novel miRNAs were identified, among which 54 were differentially expressed. Target gene prediction revealed a significant enrichment in 30 KEGG pathways, including some reproduction-related pathways, e.g. phosphatidylinositol signalling system and inositol phosphate metabolism pathways. Further analysis on six differentially expressed known miRNAs, six differentially expressed novel miRNAs and their reproduction-related putative target genes shows that both miRNAs and putative target genes showed stage-specific expression during gonadal maturation, suggesting their potential regulatory roles in sex differentiation and reproductive development. This study reveals the sex-biased miRNA profile and establishes a solid foundation for understanding the sex differentiation and gonadal maturation mechanisms of S. paramamosain.

Matched MeSH terms: Phosphatidylinositols
Fulltext Streptomyces antioxidans sp. nov., a Novel Mangrove Soil Actinobacterium with Antioxidative and Neuroprotective Potentials

Ser HL, Tan LT, Palanisamy UD, Abd Malek SN, Yin WF, Chan KG, et al.

Front Microbiol, 2016;7:899.
PMID: 27379040 DOI: 10.3389/fmicb.2016.00899

A novel strain, Streptomyces antioxidans MUSC 164(T) was recovered from mangrove forest soil located at Tanjung Lumpur, Malaysia. The Gram-positive bacterium forms yellowish-white aerial and brilliant greenish yellow substrate mycelium on ISP 2 agar. A polyphasic approach was used to determine the taxonomy status of strain MUSC 164(T). The strain showed a spectrum of phylogenetic and chemotaxonomic properties consistent with those of the members of the genus Streptomyces. The cell wall peptidoglycan was determined to contain LL-diaminopimelic acid. The predominant menaquinones were identified as MK-9(H6) and MK-9(H8), while the identified polar lipids consisted of aminolipid, diphosphatidylglycerol, glycolipid, hydroxyphosphatidylethanolamine, phospholipid, phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol and lipid. The cell wall sugars consist of galactose, glucose and ribose. The predominant cellular fatty acids (>10.0%) were identified as iso-C15: 0 (34.8%) and anteiso-C15: 0(14.0%). Phylogenetic analysis identified that closely related strains for MUSC 164(T) as Streptomyces javensis NBRC 100777(T) (99.6% sequence similarity), Streptomyces yogyakartensis NBRC 100779(T) (99.6%) and Streptomyces violaceusniger NBRC 13459(T) (99.6%). The DNA-DNA relatedness values between MUSC 164(T) and closely related type strains ranged from 23.8 ± 0.3% to 53.1 ± 4.3%. BOX-PCR fingerprints comparison showed that MUSC 164(T) exhibits a unique DNA profile, with DNA G + C content determined to be 71.6 mol%. Based on the polyphasic study of MUSC 164(T), it is concluded that this strain represents a novel species, for which the name Streptomyces antioxidans sp. nov. is proposed. The type strain is MUSC 164(T) (=DSM 101523(T) = MCCC 1K01590(T)). The extract of MUSC 164(T) showed potent antioxidative and neuroprotective activities against hydrogen peroxide. The chemical analysis of the extract revealed that the strain produces pyrazines and phenolic-related compounds that could explain for the observed bioactivities.

Matched MeSH terms: Phosphatidylinositols
Dietary Carbohydrate Promotes Cell Survival in Cancer Via the Up-Regulation of Fat Mass and Obesity-Associated Gene Expression Level

Doaei S, Gholamalizadeh M, Akbari ME, Akbari S, Feradova H, Rahimzadeh G, et al.

Malays J Med Sci, 2019 Mar;26(2):8-17.
PMID: 31447604 DOI: 10.21315/mjms2019.26.2.2

Cancer cells are mainly dependent on glycolysis for their growth and survival. Dietary carbohydrates play a critical role in the growth and proliferation of cancer and a low-carbohydrate diet may help slow down the growth of tumours. However, the exact mechanisms behind this effect are unclear. This review study aimed to investigate the effect of fat mass and obesity-associated (FTO) gene in the association between dietary carbohydrates and cancer. This study was carried out using keywords such as polymorphism and/or cancer and/or dietary carbohydrate and/or FTO gene. PubMed and Science Direct databases were used to collect all related articles published from 1990 to 2018. Recent studies showed that the level of FTO gene expression in cancer cells is dramatically increased and may play a role in the growth of these cells through the regulation of the cellular metabolic pathways, including the phosphoinositide 3-kinases/protein kinaseB (PI3K/AKT) signaling pathway. Dietary carbohydrate may influence the FTO gene expression by eliminating the inhibitory effect of adenosine monophosphate-activated protein kinase (AMPK) on the FTO gene expression. This review summarised what has been recently discovered about the effects of dietary carbohydrate on cancer cells and tried to determine the mediating role of the FTO gene in these effects.

Matched MeSH terms: Phosphatidylinositols
Fulltext Novel defect in phosphatidylinositol 4-kinase type 2-alpha (PI4K2A) at the membrane-enzyme interface is associated with metabolic cutis laxa

Mohamed M, Gardeitchik T, Balasubramaniam S, Guerrero-Castillo S, Dalloyaux D, van Kraaij S, et al.

J Inherit Metab Dis, 2020 11;43(6):1382-1391.
PMID: 32418222 DOI: 10.1002/jimd.12255

Inherited cutis laxa, or inelastic, sagging skin is a genetic condition of premature and generalised connective tissue ageing, affecting various elastic components of the extracellular matrix. Several cutis laxa syndromes are inborn errors of metabolism and lead to severe neurological symptoms. In a patient with cutis laxa, a choreoathetoid movement disorder, dysmorphic features and intellectual disability we performed exome sequencing to elucidate the underlying genetic defect. We identified the amino acid substitution R275W in phosphatidylinositol 4-kinase type IIα, caused by a homozygous missense mutation in the PI4K2A gene. We used lipidomics, complexome profiling and functional studies to measure phosphatidylinositol 4-phosphate synthesis in the patient and evaluated PI4K2A deficient mice to define a novel metabolic disorder. The R275W residue, located on the surface of the protein, is involved in forming electrostatic interactions with the membrane. The catalytic activity of PI4K2A in patient fibroblasts was severely reduced and lipid mass spectrometry showed that particular acyl-chain pools of PI4P and PI(4,5)P2 were decreased. Phosphoinositide lipids play a major role in intracellular signalling and trafficking and regulate the balance between proliferation and apoptosis. Phosphatidylinositol 4-kinases such as PI4K2A mediate the first step in the main metabolic pathway that generates PI4P, PI(4,5)P2 and PI(3,4,5)P3 . Although neurologic involvement is common, cutis laxa has not been reported previously in metabolic defects affecting signalling. Here we describe a patient with a complex neurological phenotype, premature ageing and a mutation in PI4K2A, illustrating the importance of this enzyme in the generation of inositol lipids with particular acylation characteristics.

Matched MeSH terms: Phosphatidylinositols/metabolism
The crosstalk of hedgehog, PI3K and Wnt pathways in diabetes

Benchoula K, Parhar IS, Wong EH

Arch Biochem Biophys, 2021 Feb 15;698:108743.
PMID: 33382998 DOI: 10.1016/j.abb.2020.108743

Hyperglycaemia causes pancreatic β-cells to release insulin that then attaches to a specific expression of receptor isoform and reverses high glucose concentrations. It is well known that insulin is capable of initiating insulin-receptor substrate (IRS)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) signaling pathways in target cells; such as liver, adipose tissues, and muscles. However, recent discoveries indicate that many other pathways, such as the Hedgehog (Hh) and growth factor-stimulating Wingless-related integration (Wnt) signaling pathways; are activated in hyperglycaemia as well. Although these two pathways are traditionally thought to have a decisive role in cellular growth and differentiation only, recent reports show that they are involved in regulating cellular homeostasis and energy balance. While insulin-activated IRS/PI3K/PKB pathway cascades are primarily known to reduce glucose production, it was recently discovered to increase the Hh signaling pathway's stability, thereby activating the PI3K/PKB/mammalian target of rapamycin complex 2 (mTORC2) signaling pathway. The Hh signaling pathway not only plays a role in lipid metabolism, insulin sensitivity, inflammatory response, diabetes-related complications, but crosstalks with the Wnt signaling pathway resulting in improved insulin sensitivity and decrease inflammatory response in diabetes.

Matched MeSH terms: Phosphatidylinositols