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Molecules (Basel, Switzerland) Feb 2021Varicella-zoster virus (VZV), a common and ubiquitous human-restricted pathogen, causes a primary infection (varicella or chickenpox) followed by establishment of... (Review)
Review
Varicella-zoster virus (VZV), a common and ubiquitous human-restricted pathogen, causes a primary infection (varicella or chickenpox) followed by establishment of latency in sensory ganglia. The virus can reactivate, causing herpes zoster (HZ, shingles) and leading to significant morbidity but rarely mortality, although in immunocompromised hosts, VZV can cause severe disseminated and occasionally fatal disease. We discuss VZV diseases and the decrease in their incidence due to the introduction of live-attenuated vaccines to prevent varicella or HZ. We also focus on acyclovir, valacyclovir, and famciclovir (FDA approved drugs to treat VZV infections), brivudine (used in some European countries) and amenamevir (a helicase-primase inhibitor, approved in Japan) that augur the beginning of a new era of anti-VZV therapy. Valnivudine hydrochloride (FV-100) and valomaciclovir stearate (in advanced stage of development) and several new molecules potentially good as anti-VZV candidates described during the last year are examined. We reflect on the role of antiviral agents in the treatment of VZV-associated diseases, as a large percentage of the at-risk population is not immunized, and on the limitations of currently FDA-approved anti-VZV drugs. Their low efficacy in controlling HZ pain and post-herpetic neuralgia development, and the need of multiple dosing regimens requiring daily dose adaptation for patients with renal failure urges the development of novel anti-VZV drugs.
Topics: Antiviral Agents; Encephalitis, Varicella Zoster; Herpesvirus 3, Human; Humans; Microbial Sensitivity Tests; Pyrimidine Nucleosides
PubMed: 33672709
DOI: 10.3390/molecules26041132 -
The EMBO Journal Jan 2023Reprogramming of lipid metabolism is emerging as a hallmark of cancer, yet involvement of specific fatty acids (FA) species and related enzymes in tumorigenesis remains...
Reprogramming of lipid metabolism is emerging as a hallmark of cancer, yet involvement of specific fatty acids (FA) species and related enzymes in tumorigenesis remains unclear. While previous studies have focused on involvement of long-chain fatty acids (LCFAs) including palmitate in cancer, little attention has been paid to the role of very long-chain fatty acids (VLCFAs). Here, we show that depletion of acetyl-CoA carboxylase (ACC1), a critical enzyme involved in the biosynthesis of fatty acids, inhibits both de novo synthesis and elongation of VLCFAs in human cancer cells. ACC1 depletion markedly reduces cellular VLCFA but only marginally influences LCFA levels, including palmitate that can be nutritionally available. Therefore, tumor growth is specifically susceptible to regulation of VLCFAs. We further demonstrate that VLCFA deficiency results in a significant decrease in ceramides as well as downstream glucosylceramides and sphingomyelins, which impairs mitochondrial morphology and renders cancer cells sensitive to oxidative stress and cell death. Taken together, our study highlights that VLCFAs are selectively required for cancer cell survival and reveals a potential strategy to suppress tumor growth.
Topics: Humans; Stearates; Fatty Acids; Mitochondria; Palmitates; Neoplasms
PubMed: 36408830
DOI: 10.15252/embj.2022111268 -
Current Opinion in Chemical Biology Oct 2022Raman microscopy has been used to deduce information about the distributions of endogenous biomolecules without exogenous labeling. Several functional groups, such as... (Review)
Review
Raman microscopy has been used to deduce information about the distributions of endogenous biomolecules without exogenous labeling. Several functional groups, such as alkynes (CC), nitriles (CN), and carbon-deuterium (C-D) bonds, have been employed in recent years as Raman tags to detect target molecules in cells. In this article, we review some recent advances in applications using deuterated fatty acids for lipid analysis, such as investigation of tumor-selective cytotoxicity of γ-linolenic acid (GLA), simultaneous two-color imaging of stearate and oleate using deuterated and protonated alkynes, Raman hyperspectral imaging, and analyses of the physical properties of lipids through spectral unmixing of the C-D vibrational frequencies. In addition, we review some advanced methods for observing intracellular metabolic activities, such as de novo lipogenesis from deuterium-labeled precursors.
Topics: Alkynes; Carbon; Deuterium; Fatty Acids; Nitriles; Oleic Acid; Spectrum Analysis, Raman; Stearates; gamma-Linolenic Acid
PubMed: 35792373
DOI: 10.1016/j.cbpa.2022.102181 -
Polymers Apr 2023This study presents the development of new formulations consisting of dextran (Dex) and chitosan (Ch) matrices, with fillings such as chitosan stearate (MCh), citric...
This study presents the development of new formulations consisting of dextran (Dex) and chitosan (Ch) matrices, with fillings such as chitosan stearate (MCh), citric acid, salicylic acid, or ginger extract. These materials were characterized using Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and mechanical tests, and evaluated for antioxidant properties, including scavenging activities, metal chelation, and ferric ion reducing power, as well as anti-inflammatory properties, measuring the binding affinity between serum albumin and the bioactive substances, which can influence their bioavailability, transport, and overall anti-inflammatory effect. Compounds in ginger such as 6-gingerol reduce inflammation by inhibiting the production of inflammatory substances, such as prostaglandin, cytokines, interleukin-1β, and pro-inflammatory transcription factor (NF-κB) and, alongside citric and salicylic acids, combat oxidative stress, stabilizes cell membranes, and promote membrane fluidity, thereby preserving membrane integrity and function. Incorporating chitosan stearate in chitosan:dextran samples created a dense, stiff film with an elastic modulus approximately seventeen times higher than for the chitosan:dextran matrix. The Dex:Ch:MCh sample exhibited low compressibility at 48.74 ± 1.64 kPa, whereas the Dex:Ch:MCh:citric acid:salicylic acid composite had a compact network, allowing for 70.61 ± 3.9% compression at 109.30 kPa. The lipid peroxidation inhibitory assay revealed that Dex:Ch:MCh:citric acid had the highest inhibition value with 83 ± 0.577% at 24 h. The study highlights that adding active substances like ginger extract and citric acid to Dex:Ch composites enhances antioxidant properties, while modified chitosan improves mechanical properties. These composites may have potential medical applications in repairing cell membranes and regulating antioxidant enzyme activities.
PubMed: 37177127
DOI: 10.3390/polym15091980 -
Scientific Reports Nov 2022Appendicoliths are commonly found obstructing the lumen of the appendix at the time of appendectomy. To identify factors that might contribute to their formation we...
Appendicoliths are commonly found obstructing the lumen of the appendix at the time of appendectomy. To identify factors that might contribute to their formation we investigated the composition of appendicoliths using laser ablation inductively coupled plasma mass spectroscopy, gas chromatography, polarized light microscopy, X-ray crystallography and protein mass spectroscopy. Forty-eight elements, 32 fatty acids and 109 human proteins were identified within the appendicoliths. The most common elements found in appendicoliths are calcium and phosphorus, 11.0 ± 6.0 and 8.2 ± 4.2% weight, respectively. Palmitic acid (29.7%) and stearate (21.3%) are the most common fatty acids. Some stearate is found in crystalline form-identifiable by polarized light microscopy and confirmable by X-ray crystallography. Appendicoliths have an increased ratio of omega-6 to omega-3 fatty acids (ratio 22:1). Analysis of 16 proteins common to the appendicoliths analyzed showed antioxidant activity and neutrophil functions (e.g. activation and degranulation) to be the most highly enriched pathways. Considered together, these preliminary findings suggest oxidative stress may have a role in appendicolith formation. Further research is needed to determine how dietary factors such as omega-6 fatty acids and food additives, redox-active metals and the intestinal microbiome interact with genetic factors to predispose to appendicolith formation.
Topics: Humans; Fatty Acids; Stearates; Appendix; Appendectomy; Chromatography, Gas
PubMed: 36396724
DOI: 10.1038/s41598-022-21397-9 -
The Journal of Biological Chemistry Jul 2023Skeletal muscle consists of both fast- and slow-twitch fibers. Phospholipids are important structural components of cellular membranes, and the diversity of their fatty...
Skeletal muscle consists of both fast- and slow-twitch fibers. Phospholipids are important structural components of cellular membranes, and the diversity of their fatty acid composition affects membrane characteristics. Although some studies have shown that acyl chain species in phospholipids differ among various muscle fiber types, the mechanisms underlying these differences are unclear. To investigate this, we analyzed phosphatidylcholine (PC) and phosphatidylethanolamine (PE) molecules in the murine extensor digitorum longus (EDL; fast-twitch) and soleus (slow-twitch) muscles. In the EDL muscle, the vast majority (93.6%) of PC molecules was palmitate-containing PC (16:0-PC), whereas in the soleus muscle, in addition to 16:0-PC, 27.9% of PC molecules was stearate-containing PC (18:0-PC). Most palmitate and stearate were bound at the sn-1 position of 16:0- and 18:0-PC, respectively, and 18:0-PC was found in type I and IIa fibers. The amount of 18:0-PE was higher in the soleus than in the EDL muscle. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) increased the amount of 18:0-PC in the EDL. Lysophosphatidylglycerol acyltransferase 1 (LPGAT1) was highly expressed in the soleus compared with that in the EDL muscle and was upregulated by PGC-1α. LPGAT1 knockout decreased the incorporation of stearate into PC and PE in vitro and ex vivo and the amount of 18:0-PC and 18:0-PE in murine skeletal muscle with an increase in the level of 16:0-PC and 16:0-PE. Moreover, knocking out LPGAT1 decreased the amount of stearate-containing phosphatidylserine (18:0-PS), suggesting that LPGAT1 regulated the acyl chain profiles of phospholipids, namely, PC, PE, and PS, in the skeletal muscle.
Topics: Animals; Mice; Muscle Fibers, Fast-Twitch; Muscle Fibers, Slow-Twitch; Muscle, Skeletal; Phosphatidylcholines; Phospholipids; Stearates; Plasmalogens; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Muscle Fibers, Skeletal
PubMed: 37217003
DOI: 10.1016/j.jbc.2023.104848 -
Foods (Basel, Switzerland) Jan 2024Different structural composition ratios of sucrose stearates with hydrophilic-hydrophobic balance (HLB) values ranging from 1 to 16 on lipolysis in emulsion were...
Different structural composition ratios of sucrose stearates with hydrophilic-hydrophobic balance (HLB) values ranging from 1 to 16 on lipolysis in emulsion were investigated using a simulated gastrointestinal tract (GIT). Results showed a direct correlation between the HLB values of sucrose stearates and the lipolysis rate of emulsions, and a lower HLB value led to diminished lipolysis in the GIT simulation model. Mechanism study indicated that poor emulsifying capacity of sucrose stearates and lipolysis of sucrose stearates with lower HLB value inhibited the digestive behavior of oil. In addition, monoester was mainly hydrolyzed in the gastric phase, whereas sucrose polyesters caused lipolysis in the intestinal phase using an in vitro digestive model and HPLC analysis, further suppressing lipid digestion. Furthermore, a decrease in cell cytotoxicity and proinflammatory effects on Caco-2 and Raw264.7 were observed post-digestion, respectively. This work offers important insights into the effects of the degree of esterification of sucrose stearate on lipid digestion behavior in oil-in-water emulsions.
PubMed: 38201202
DOI: 10.3390/foods13010175 -
International Journal of Biological... 2023Cellular senescence is a state of proliferative arrest, and the development of carcinoma can be suppressed by conferring tumor cell senescence. Recently, we found that...
Cellular senescence is a state of proliferative arrest, and the development of carcinoma can be suppressed by conferring tumor cell senescence. Recently, we found that carnitine palmitoyltransferase 1C (CPT1C) controls tumor cell proliferation and senescence via regulating lipid metabolism and mitochondrial function. Here, C-metabolic flux analysis (C-MFA) was performed and the results revealed that knockdown in MDA-MB-231 cells significantly induced cellular senescence accompanied by altered fatty acid metabolism. Strikingly, stearate synthesis was decreased while oleate was increased. Furthermore, stearate significantly inhibited proliferation while oleate reversed the senescent phenotype induced by silencing in MDA-MB-231 cells as well as PANC-1 cells. A939572, an inhibitor of stearoyl-Coenzyme A desaturase 1, had the same effect as stearate to inhibit cellular proliferation. These results demonstrated that stearate and oleate are involved in CPT1C-mediated tumor cellular senescence, and the regulation of stearate/oleate rate via inhibition of SCD-1 could be an additional strategy with depletion of CPT1C for cancer therapy.
Topics: Humans; Oleic Acid; Stearates; Metabolic Flux Analysis; Carnitine O-Palmitoyltransferase; Neoplasms; Cellular Senescence
PubMed: 37151873
DOI: 10.7150/ijbs.80822 -
Metabolites Jan 2020This study aimed to explore the dynamic changes in metabolite profiles and metabolism pathways in the serum of growing pigs by intravenous infusion of sodium butyrate...
This study aimed to explore the dynamic changes in metabolite profiles and metabolism pathways in the serum of growing pigs by intravenous infusion of sodium butyrate (SB). Fourteen crossbred growing barrows (BW = 23.70 ± 1.29 kg) fitted with jugular cannula were randomly allocated to the SB and control (Con) groups, each group consisted of seven replicates (pens), with one pig per pen. At 9:00 of each day during the experimental period, pigs in the SB group were infused with 10 mL of SB (200 mmol/L, pH 7.4, 37 °C) via precaval vein, while the Con group was treated with the same volume of physiological saline. On day 4, the blood of each pig was collected at 0, 30, 60, and 120 min after the intravenous infusion. Metabolites in the serum were detected by gas chromatograph-mass spectrometry analysis. Pathway analysis of metabolomic profiles showed that the differential metabolites mainly enriched in amino acid metabolism, lipid-related metabolism, and the tricarboxylic acid (TCA) cycle. More importantly, the relative concentrations of all eight essential amino acids, five non-essential amino acids, and two amino acid derivatives were decreased by the parenteral SB. In addition, SB significantly increased the relative concentrations of eicosanoic acid and octadecanoic acid and decreased the relative concentration of glycerol-3-phosphate at 0 min (three days after intravenous infusion of SB), which suggests that parenteral SB may increase stearates mobilization and decrease the biosynthesis of stearates. In conclusion, intravenous infusion of SB may induce more amino acids to synthesize proteins and affect fat metabolism through increasing fat mobilization and decreasing the biosynthesis of stearates. However, a further study is needed to understand the mechanism of extensive metabolic pathway changes induced by parenteral SB.
PubMed: 31906303
DOI: 10.3390/metabo10010020 -
Marine Drugs Jun 2021Some commonly used surfactants in cosmetic products raise concerns due to their skin-irritating effects and environmental contamination. Multifunctional,...
Some commonly used surfactants in cosmetic products raise concerns due to their skin-irritating effects and environmental contamination. Multifunctional, high-performance polymers are good alternatives to overcome these problems. In this study, agarose stearate (AS) with emulsifying, thickening, and gel properties was synthesized. Surfactant-free cosmetic formulations were successfully prepared from AS and carbomer (CBM) mixed systems. The correlation of rheological parameter with skin feeling was determined to study the usability of the mixed systems in cosmetics. Based on rheological analysis, the surfactant-free cosmetic cream (SFC) stabilized by AS-carbomer showed shear-thinning behavior and strongly synergistic action. The SFC exhibited a gel-like behavior and had rheological properties similar to commercial cosmetic creams. Scanning electron microscope images proved that the AS-CBM network played an important role in SFC's stability. Oil content could reinforce the elastic characteristics of the AS-CBM matrix. The SFCs showed a good appearance and sensation during and after rubbing into skin. The knowledge gained from this study may be useful for designing surfactant-free cosmetic cream with rheological properties that can be tailored for particular commercial cosmetic applications. They may also be useful for producing medicine products with highly viscous or gel-like textures, such as some ointments and wound dressings.
Topics: Acrylic Resins; Cosmetics; Excipients; Gels; Humans; Microscopy, Electron, Scanning; Rheology; Sepharose; Skin Cream; Spectroscopy, Fourier Transform Infrared; Surface-Active Agents; Viscoelastic Substances
PubMed: 34208474
DOI: 10.3390/md19060344