Fatty Acid Derivatives Research Articles

Chemical composition and antibacterial activity of coconut-shell liquid smoke to maintain the texture of fresh meat

This research focused on the evaluation of raw broiler chicken meat texture and pathogenic antibacterial effect under the treatment of grade 2 coconut-shell liquid smoke (CSLS) as a food preservative. Compound identification of grade 2 CSLS was conducted using the GC-MS method. The main chemical compounds of CSLS were polyunsaturated fatty acid derivates, fatty acid and phenol. The evaluation of texture was conducted on raw broiler chicken meat under the treatment of grade 2 CSLS during storage at 25 ℃ for 7 days. The effect of antibacterial activity of grade 2 CSLS with different concentration (i.e., 5%, 25%, 50%, and 75%) were tested using Gram-positive bacteria on several pathogenic bacteria such as L. monocytogenes, S. aureus, P. Aeruginosa, and E. coli. The results indicated that grade 2 CSLS influenced the inhibited zone of L. monocytogenes, S. aureus, P. Aeruginosa, and E. coli respectively with linear correlation. The optimal concentration of grade 2 CSLS resulted in a concentration of 50%, which was the most optimal against L. monocytogenes, S. aureus, P. Aeruginosa, and E. coli as pathogenic bacteria strains.

Antimicrobial, antifungal, antioxidant activity and phytochemical investigation of fatty acids by GS/MS of raspberry (Rubus idaeus L.) shoot lipophilic extract

The aim of the study was to determine the content of fatty acids using GC-MS in the obtained extract, conduct a study of the antimicrobial, antifungal and antioxidant activities of Rubus idaeus shoot lipophilic extract. The quantification of fatty acids was accomplished through GC-MS, antioxidant activity was assessed by potentiometric method, antimicrobial and antifungal activity was determined by well method. The 18 compounds were identified by the GS-MS. The levulenic acid (64.47±0.08 mg/100 g), linoleic acid (8.50±0.08 mg/100 g) and linolenic acid (6.80±0.04 mg/100 g) dominated in the obtained lipophilic R. idaeus shoot extract. Bacillus subtilis (17.00±0.50 mm) was the most sensitive to lipophilic extract whereas P. vulgaris was the most resistant to the lipophilic extract. Moreover, Candida albicans was medium sensitive to lipophilic extract (13.50±0.50 mm). The antioxidant activity was 1.00 mmol equiv./mdry res, according to Maslov`s antioxidant level classification it has low level. The extract exhibited antimicrobial activity against all tested strains, with the most significant impact observed against B. subtilis. However, the obtained lipophilic extract showed a relatively low level of antioxidant activity. Consequently, the derivatives of fatty acids play a substantial role in the antimicrobial and antifungal effects, whereas their contribution to antioxidant activity appears to be limited.

The Environmental Pollutant NO3⋅ Rapidly Damages Alkene Moieties in Lipids Through Electron Transfer

AbstractThe presence of alkene moieties in fatty acids of (phospho)lipids and cholesterol derivatives makes them highly susceptible to damage by nitrate radicals (NO3⋅), potentially formed through simultaneous exposure to the environmental air pollutants nitrogen dioxide (NO2⋅) and ozone (O3). Absolute rate coefficients derived from reactions with simplified model systems range from 4 to 8×109 M−1 s−1 in acetonitrile, ranking among the highest determined for NO3⋅ reactions with biomolecules in solution to date. Alkenes featuring an electron‐withdrawing carbonyl substituent also display notable reactivity with k values of (2.5±1.0)×108 M−1 s−1. Calculations suggest that these reactions are initiated by oxidative electron transfer (ET) involving the C=C bond, followed by recombination of the resulting alkene radical cation with nitrate anion (NO3−) to form the nitrate adduct radical as the kinetically controlled product. Conversely, saturated fatty acid derivatives and cholestanol react with NO3⋅ through hydrogen atom transfer (HAT) with rate coefficients of 106–107 M−1 s−1, indicating that biomolecules with a considerable number of non‐ or moderately activated sp3 C−H bonds are also highly susceptible to NO3⋅ attack. These findings underscore the potential health hazards associated with exposure to combined NO2⋅ and O3 gases.

Phytochemical Volatiles as Potential Bionematicides with Safer Ecotoxicological Properties.

The management of plant-parasitic nematodes (PPNs) still relies on traditional nematicides that threaten the environment and human health. Novel solutions are urgently needed for PPN pest management that are effective while safeguarding non-target organisms. Volatile phytochemicals belong to a structurally diverse group of bioactive metabolites that are believed to hold safer environmental characteristics than synthetic pesticides. Nonetheless, not many studies have analysed the potential environmental benefits of shifting to these novel bionematicides. In the present study, 20 phytochemical volatiles with reported nematicidal activity were compared to traditional pesticides using specific parameters of environmental and human health safety available on applied online databases and predicted in silico through specialised software. Overall, the reviewed nematicidal phytochemicals were reportedly less toxic than synthetic nematicides. They were predicted to disperse to the air and soil environmental compartments and were reported to have a lower toxicity on aquatic organisms. On the contrary, the synthetic nematicides were reportedly toxic to aquatic organisms while showing a predicted high affinity to the water environmental compartment. As alternatives, β-keto or fatty acid derivatives, e.g., aliphatic alcohols or ketones, showed more adequate properties. This study highlights the importance of complementing studies on nematicidal activity with a risk assessment-based analysis to allow for a faster selection of nematicidal phytochemical volatiles and to leverage the development and implementation of bionematicides.

The Ameliorating Effect of Artificial Coffee from Mangrove Fruits (Rhizophora mucronata) on T Lymphocyte Cells and Renal Histopathology of BALB/c Mice Induced by Lipopolysaccharide

The potential of Rhizophora mucronata mangrove fruits as antioxidants is noteworthy, with promising prospects as nutraceuticals, particularly in their role as immunomodulators for T lymphocyte cells. R. mucronata fruits have been utilized by household industries in Indonesia as a coffee-like drink (artificial coffee). This study aims to determine the ability of mangrove fruit artificial coffee R. mucronata to stimulate T lymphocyte cells and renal histopathology conditions in LPS-induced mice animal models. This study also characterizes proximate characteristics, antioxidant capacity, and Gas Chromatography-Mass Spectrometry (GC-MS) screening of mangrove fruit artificial coffee compounds. The stages of this research included the process of mangrove fruit artificial coffee; analysis of proximate and caffeine; compounds screening (GC-MS) and toxicity prediction (Pro-Tox II); antioxidant capacity (DPPH); T lymphocyte cell expression (flow cytometry); and renal histopathological evaluation. The results showed moisture content (5.22±0.20%); ash (5.17±0.27%); protein (13.74±0.24%); fat (11.63±0.32%); carbohydrate (64.23±0.15%), caffeine (1.09±0.04%). GC-MS analysis showed that the compounds contained in artificial coffee were derivatives of fatty aldehyde, fatty acid, and cycloalkanes compound classes. Predicted toxicity of artificial coffee LD50 5000 mg/kg. Antioxidant capacity is classified as moderate (IC50 119.41±0.99µg/mL). Mangrove fruit artificial coffee can increase the relative number of CD4+CD62L+ by 14.68-29.48% and CD8+CD62L+ T lymphocyte cells by 12.60-30.33%. Artificial coffee can also increase the number of healthy cells and reduce the cells that undergo necrosis in the renal of LPS-induced mice. This study concluded that mangrove fruit artificial coffee R. mucronata positively affects T lymphocyte activation and mice renal cells’ protection from necrosis due to LPS induction.

UPLC-qTOF-MS phytochemical profile of Commiphora gileadensis leaf extract via integrated ultrasonic-microwave-assisted technique and synthesis of silver nanoparticles for enhanced antibacterial properties

The utilization of metallic nanoparticles in bio-nanofabrication holds significant potential in the field of applied research. The current study applied and compared integrated ultrasonic-microwave-assisted extraction (US/MICE), ultrasonic extraction (USE), microwave-assisted extraction (MICE), and maceration (MAE) to extract total phenolic content (TPC). In addition, the study examined the antioxidant activity of Commiphora gileadensis (Cg) leaf. The results demonstrated that the TPC of US/MICE exhibited the maximum value at 59.34 ± 0.007 mg GAE/g DM. Furthermore, at a concentration of 10 μg/mL, TPC displayed a significant scavenging effect on DPPH (56.69 %), with an EC50 (6.48 μg/mL). Comprehensive metabolite profiling of the extract using UPLC-qTOF-MS/MS was performed to identify active agents. A total of 64 chromatographic peaks were found, out of which 60 were annotated. The most prevalent classes of metabolites found were polyphenols (including flavonoids and lignans), organic compounds and their derivatives, amides and amines, terpenes, and fatty acid derivatives. Transmission electron microscopy (TEM) revealed the aggregate size of the synthesized nanoparticles and the spherical shape of C. gileadensis-mediated silver nanoparticles (Cg-AgNPs). The nanoparticles had a particle size ranging from 7.7 to 42.9 nm. The Cg-AgNPs exhibited more inhibition zones against S. aureus and E. coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Cg-extract, AgNPs, and Cg-AgNPs were also tested. This study demonstrated the feasibility of using combined ultrasonic-microwave-assisted extraction to separate and extract chemicals from C. gileadensis on a large scale. These compounds have potential use in the pharmaceutical industry. Combining antibacterial and biocompatible properties in materials is vital for designing new materials for biomedical applications. Additionally, the results showed that the biocompatibility of the Ag-NPs using C. gileadensis extracts demonstrated outstanding antibacterial properties.

Volatile Profiles and DNA Barcodes of Myrtaceae Species with Occurrence in the Brazilian Amazon.

Myrtaceae family includes many species with taxonomic challenges, making it one of the most complex families to identify. This study used DNA barcoding to find molecular markers for species authentication based on the Myrtaceae family's chemical composition and genetic diversity. Essential oils and genetic material were extracted from the leaves of six different species: Eugenia uniflora, E. patrisii, Myrcia splendens, Psidium guajava, P. guineense, and Psidium sp. The samples were analyzed based on compound classes and grouped into two categories. Group I included samples with high amounts of oxygenated sesquiterpenes (3.69-76.05 %) and fatty acid derivatives (0.04-43.59 %), such as E. uniflora, Myrcia splendens, and E. patrisii. Group II included samples P. guajava, P. guineense, and Psidium sp., which had a significant content of monoterpene hydrocarbons (0.69-72.35 %), oxygenated sesquiterpenes (8.06-68.1 %), phenylpropanoids (0.45-22.59 %), and sesquiterpene hydrocarbons (0.27-21.84 %). The PsbA-trnH gene sequences had a high genetic variability, allowing the species to be distinguished. A phylogenetic analysis showed two main clusters with high Bootstrap values corresponding to the subtribes Eugeniineae, Myrciinae, and Pimentinae. The results suggest a weak correlation between genetic and chemical data in these Myrtaceae species.

Volatile Constituents of Some Myrtaceous Edible and Medicinal Fruits from the Brazilian Amazon.

Native and exotic fruits from the Amazon have varied characteristics, with aroma being a decisive factor in their acceptance for medicinal use as a nutraceutical supplement. This work aimed to analyze the chemical constituents of the volatile concentrates of some Myrtaceous fruit species sampled in the Brazilian Amazon. The fruit's pulps were subjected to simultaneous distillation-extraction, and gas chromatography-mass spectrometry was used to analyze their volatile chemical composition. In the volatile concentrate of Eugenia stipitata (Araçá-boi) α-pinene (17.5%), citronellyl butanoate (15.6%), and pogostol (13.5%) were identified as primary constituents; Eugenia uniflora (Ginja) concentrate comprised curzerene (30.5%), germacrone (15.4%), atractylone (13.1%), and (E)-β-ocimene (11.1%); in Myrciaria dubia (Camu-Camu), α-pinene (55.8%), (E)-β-ocimene (13.1%), and α-terpineol (10.0%) were present; in Psidium guajava (Goiaba) were (2E)-hexenal (21.7%), hexanal (15.4%), caryophylla-4(12),8(13)-dien-5-β-ol (10.5%), caryophyllene oxide (9.2%), and pogostol (8.3%); and in Psidium guineense (Araçá), limonene (25.2%), ethyl butanoate (12.1%), epi-β-bisabolol (9.8%), and α-pinene (9.2%) were the main constituents. The analyzed volatile concentrates of these fruit species presented a significant diversity of constituents with a predominance of functional groups, such as monoterpenes, sesquiterpenes, and fatty acid derivatives, originating from the plant's secondary metabolism and playing an important role in their nutritional and medicinal uses.

Metabolomic responses of tea [Camellia sinensis (L.) O. Kuntze] leaves to red spider mite [Oligonychus coffeae (Nietner)] and tea mosquito bug [Helopeltis theivora Waterhouse] infestation: a GC–MS-based study

BackgroundThe tea plant, Camellia sinensis (L.) O. Kuntze, is an evergreen leafy plant whose tender leaves are used in the manufacturing of the world’s second most consumed beverage—tea. The production and consumption of tea worldwide have continually increased over the decades. All parts of the plant—leaf, stem, root, flower and seed, are fed upon by insect pests. This study elucidates the metabolomic changes occurring in tea leaves in response to infestation by two major pests in tea gardens: red spider mites and tea mosquito bugs. These pests significantly impact both the quantity and quality of tea production. The secondary metabolites produced by the tea due to pest attack has been analysed using GC–MS analysis in the laboratory.ResultsMostly fatty acid derivatives were biosynthesized as secondary metabolites due to pest attack as revealed from the result. In both infestations, methyl stearate was found to be produced along with increased chromatographic peaks of compounds such as caffeine, methyl palmitate, methyl linoleate, and stigmasta-7,25-dien-3-ol. In comparison with respective control samples (leaf with no pest attack), the one attacked by red spider mite showed eighteen exclusive metabolites, whereas tea mosquito bug infested leaf showed six such exclusive metabolites.ConclusionsSome metabolites were found to be either increased or decreased in their amount in both the samples. The increased compounds were reported with insecticidal and pesticidal properties with respect to respective controls. Some metabolites were markers of pest attacks i.e. plant defense mechanism induced phytochemicals according to the literature as discussed in this research.

Abstract PO5-23-11: Elevated linoleic acid levels in red blood cells membrane predicts response to neoadjuvant chemotherapy in breast cancer patients

Abstract Introduction: Fatty acids (FA) consumed in the diet have been implicated in increasing the risk of breast cancer (BC). Humans have a wide variety of FAs, including saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) FAs. PUFAs can be further classified into omega-3 (n-3) and omega-6 (n-6) PUFAs. While n-3 has been associated with reducing inflammation and promoting apoptosis in BC cells, n-6 has been linked to increased inflammation, oxidative stress, and the promotion of BC cell proliferation and treatment resistance. In healthy women, the n-3 content in mammary tissue correlates with n-3 content in red blood cells (RBCs). The FA profile of the RBC membrane provides an unbiased option to assess lipid intake and composition, reflecting long-term FA intake and providing an objective and sensitive measure of lipid intake and body fat deposits. Notably, BC patients have been found to display a high n-6:n-3 ratio in RBCs, which is associated with inflammatory and oxidative stress biomarkers. The neoadjuvant chemotherapy treatment (NACT) model presents a unique opportunity to study resistance mechanisms in non-metastatic BC patients. In this approach, the absence of tumor (pathologic complete response: pCR, or Residual Cancer Burden (RCB) = 0) after NACT indicates treatment sensitivity and better overall survival (OS). Objective: The objective of this study is to determine whether differences in FA profiles determined in the RBC membrane and plasma are associated with the response to NACT in non-metastatic BC patients. Methods: A prospective study was conducted, including non-metastatic BC patients scheduled to receive NACT. Blood samples were collected before the first cycle of NACT to measure plasma and RBC FA derivatives, SFAs, MUFAs, and PUFAs. The pathological complete response (pCR) and residual cancer burden (RCB) were assessed. Results: A total of twenty-eight BC patients were included in the study. When comparing pCR vs. no-pCR using total SFA, MUFA, and PUFA plasma samples, no significant differences were observed. However, in RBC, an increase in PUFA was associated with a higher rate of no-pCR (**p< 0.01). Furthermore, comparing omega-6 and omega-3 (both PUFA) levels, an increase in omega-6 was associated with no-pCR (**p< 0.01), while no significant differences were observed with omega-3. No differences were obtained in plasma samples for either omega-6 and omega-3. To determine which specific omega-6 PUFAs were responsible for the association with no-pCR, elevated levels of linoleic acid (LA) in RBC were found to be associated with no-pCR (**p< 0.01). Other omega-6 PUFAs, including gamma-linolenic acid (GLA), eicosadienoic acid (EDA), dihomo-gamma linolenic acid (DGLA), and arachidonic acid (ARA), showed no significant associations. Multivariate and regression analysis confirmed LA (C18:2 n-6, LA) as the most relevant FA when assessing RCB (0-1 vs. 2-3) in RBC membranes, but not in plasma. The receiver operating characteristic (ROC) curve analyzing LA levels in RBC showed an area under the curve (AUC) of 0.855 for RCB (sensitivity: 76.9%, specificity: 92.3%). Conclusions: To the best of our knowledge, this is the first study demonstrating a clear connection between RBC membrane FA composition, specifically LA concentration, and the pathological response in BC patients after NACT. The measurements taken in plasma did not show significant associations, suggesting that RBC membrane FA profile of could serve as a relevant prognostic biomarker for studying resistance mechanisms to NACT in early BC patients Table. Measured FAs in RBC membrane and plasma by pathologic complete response *Indicates p<0.05; abbreviations: pCR: pathological complete response; SD: standard deviation; yr: years; BMI: body mass index; HR: hormone receptor; HER2: human epidermal growth factor receptor type-2; NLR: neutrophil to lymphocyte ratio; HG: histological grade; RCB: residual cancer burden; NA: not applicable Citation Format: Benjamin Walbaum, César Sánchez, Francisco Acevedo. Elevated linoleic acid levels in red blood cells membrane predicts response to neoadjuvant chemotherapy in breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-23-11.

Unveiling the formation capacity of multicomponent oleogels: Performance of lecithin interacting with monostearate derivatives

Oleogels have been explored as fat substitutes due to their healthier composition compared to trans and saturated fats, also presenting interesting technological perspectives. The aim of this study was to investigate the compositional perspective of multicomponent oleogels. Structuring ability of lecithin (LEC) (20 or 90 wt% of phosphatidylcholine – PC) combined with glycerol monostearate (GMS), sorbitan monostearate (SMS) or sucrose monostearate (SAC) in sunflower oil was evaluated from oleogels properties. The thermal and rheological properties, microstructure and stability of the oleogels were affected by the difference in the chemical composition of LEC and the ratio between LEC and different surfactants. Interestingly, low-phosphatidylcholine LEC (L20) performed better, although systems formed with reduced amounts of LEC tended to be softer (LEC-GMS) and present high oil holding capacity (LEC-SMS). The mixtures of LEC and monostearate-based surfactants showed different behaviors, depending on the surfactant polar head. In LEC-GMS systems, LEC hindered the self-assembly of GMS in sunflower oil, compromising mechanical properties and increasing oil release. When combined with SMS, LEC acted as a crystal habit modifier of SMS, forming a more homogeneous microstructure and producing stronger oleogels with greater oil binding capacity. However, above the threshold concentration, LEC prevented SMS self-assembly, resulting in a weaker gel. A positive interaction was found in LEC-SAC formulations in specific ratios, since SAC cannot act as a single oleogelator. Results show the impact of solubility balance played by LEC and fatty-acid derivatives surfactant when combined and used as oleogelators. This knowledge can contribute to a rational perspective in the preparation and modulation of the properties of edible oleogels.

Unsaturated Fatty Acid Synthesis Is Associated with Worse Survival and Is Differentially Regulated by MYCN and Tumor Suppressor microRNAs in Neuroblastoma.

MYCN amplification (MNA) and disruption of tumor suppressor microRNA (TSmiR) function are key drivers of poor outcomes in neuroblastoma (NB). While MYCN and TSmiRs regulate glucose metabolism, their role in de novo fatty acid synthesis (FAS) and unsaturated FAS (UFAS) remains poorly understood. Here, we show that FAS and UFAS (U/FAS) genes FASN, ELOVL6, SCD, FADS2, and FADS1 are upregulated in high-risk (HR) NB and that their expression is associated with lower overall survival. RNA-Seq analysis of human NB cell lines revealed parallel U/FAS gene expression patterns. Consistent with this, we found that NB-related TSmiRs were predicted to target these genes extensively. We further observed that both MYC and MYCN upregulated U/FAS pathway genes while suppressing TSmiR host gene expression, suggesting a possible U/FAS regulatory network between MYCN and TSmiRs in NB. NB cells are high in de novo synthesized omega 9 (ω9) unsaturated fatty acids and low in both ω6 and ω3, suggesting a means for NB to limit cell-autonomous immune stimulation and reactive oxygen species (ROS)-driven apoptosis from ω6 and ω3 unsaturated fatty acid derivatives, respectively. We propose a model in which MYCN and TSmiRs regulate U/FAS and play an important role in NB pathology, with implications for other MYC family-driven cancers.

Hair Product Allergy: A Review of Epidemiology and Management.

Allergy to hair products is an increasingly common issue among people given the exposure to these products on a daily basis. Allergic reactions could be in the form of delayed-type contact dermatitis or the form of immediate-type hypersensitivity reactions. Hair products contain many ingredients and chemicals that patients may have allergies to, but common allergens are hair dyes, fragrances, persulfate salts, ammonium thioglycolate, coconut fatty acid derivatives, and acrylates. Allergy to hair dye is the most common followed by other allergens such as fragrances and persulfate salts. We discussed testing for hair dye allergy along with suggestions for alternative hair dyes that patients may use.Allergy to topical scalp medications is also seen in patients using those products. Allergy to topical minoxidil is seen more often due to the increased use of minoxidil sprays and foams among patients to increase hair growth. We will discuss in this review the diagnosis and alternatives for patients with minoxidil allergy. Hairdressers are at higher risk of allergy to hair products compared to the general population due to prolonged exposure to allergens and specific measures should be implemented to minimize the hazards of exposure.

Visceral adipose of obese mice inhibits endothelial inwardly rectifying K+ channels in a CD36-dependent fashion.

Obesity imposes deficits on adipose tissue and vascular endothelium, yet the role that distinct adipose depots play in mediating endothelial dysfunction in local arteries remains unresolved. We recently showed that obesity impairs endothelial Kir2.1 channels, mediators of nitric oxide production, in arteries of visceral adipose tissue (VAT), while Kir2.1 function in subcutaneous adipose tissue (SAT) endothelium remains intact. Therefore, we determined if VAT versus SAT from lean or diet-induced obese mice affected Kir2.1 channel function in vitro. We found that VAT from obese mice reduces Kir2.1 function without altering channel expression whereas AT from lean mice and SAT from obese mice had no effect on Kir2.1 function as compared to untreated control cells. As Kir2.1 is well known to be inhibited by fatty acid derivatives and obesity is strongly associated with elevated circulating fatty acids, we next tested the role of the fatty acid translocase CD36 in mediating VAT-induced Kir2.1 dysfunction. We found that the downregulation of CD36 restored Kir2.1 currents in endothelial cells exposed to VAT from obese mice. In addition, endothelial cells exposed to VAT from obese mice exhibited a significant increase in CD36-mediated fatty acid uptake. The importance of CD36 in obesity-induced endothelial dysfunction of VAT arteries was further supported in ex vivo pressure myography studies where CD36 ablation rescued the endothelium-dependent response to flow via restoring Kir2.1 and endothelial nitric oxide synthase function. These findings provide new insight into the role of VAT in mediating obesity-induced endothelial dysfunction and suggest a novel role for CD36 as a mediator of endothelial Kir2.1 impairment.NEW & NOTEWORTHY Our findings suggest a role for visceral adipose tissue (VAT) in the dysfunction of endothelial Kir2.1 in obesity. We further reveal a role for CD36 as a major contributor to VAT-mediated Kir2.1 and endothelial dysfunction, suggesting that CD36 offers a potential target for preventing the early development of obesity-associated cardiovascular disease.

Abstract LB295: Unsaturated fatty acid synthesis is associated with poor prognosis and is differentially regulated by MYCN and tumor suppressor microRNAs in neuroblastoma

Abstract Dysregulated metabolism is a hallmark of cancer. While the role of glucose metabolism in cancer has been extensively studied, relatively little has been done to understand the role of poly-unsaturated fatty acids in cancer biology. To gain insight into their contribution to cancer progression we determined the expression patterns and outcome associations of both saturated and unsaturated fatty acid synthesis (UFAS) genes in pediatric neuroblastoma (NB), and fatty acid levels in NB cell lines derived from high-risk tumors. MYCN amplification and disruption of tumor suppressor miRNAs (TSmiR) function are central drivers of poor outcomes in NB. MYC, MYCN, and TSmiRs regulate glucose metabolism; however, their role in UFAS remains poorly understood. Using complementary analysis of publicly available genomic datasets and cultured NB cell measurements we examined the potential regulation of UFAS genes through MYCN and MYC activity and posttranscriptional regulation by TSmiRs. Here we show that de novo and UFAS pathway genes FASN, ELOVL6, SCD, FADS2, and FADS1 are upregulated in high-risk NB and are associated with poor prognosis. RNA-Seq analysis of eight human NB cell lines revealed parallel UFAS gene expression patterns. Consistent with this, we found that NB-related TSmiRs were predicted to extensively target these genes. Additionally, we observed that both MYC and MYCN upregulated UFAS pathway genes while suppressing TSmiR host gene expression, thereby creating a possible UFAS regulatory network between MYCN and TSmiRs in NB. Furthermore, using mass spectrometry analysis we found NB cells to be high in de novo synthesized omega 9 (ω9) unsaturated fatty acids and low in both ω6 and ω3. This finding provides a plausible means for NB to limit cell-autonomous immune stimulation and reactive oxygen species (ROS)-driven apoptosis from ω6 and ω3 unsaturated fatty acid derivatives, respectively. We propose a model in which the UFAS pathway, through novel regulation by MYCN and TSmiRs, plays a key role in neuroblastoma pathology with implications for other MYC-driven cancers. Citation Format: Dennis A. Sheeter, Secilia Garza, Hui Gyu Park, Lorraine-Rana Benhamou, Nikki R. Badi, Erika C. Espinosa, Kumar Kothapalli, J. Thomas Brenna, John T. Powers. Unsaturated fatty acid synthesis is associated with poor prognosis and is differentially regulated by MYCN and tumor suppressor microRNAs in neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB295.

Insect immune resolution with EpOME/DiHOME and its dysregulation by their analogs leading to pathogen hypersensitivity

Upon immune challenge, recognition signals trigger insect immunity to remove the pathogens through cellular and humoral responses. Various immune mediators propagate the immune signals to nearby tissues, in which polyunsaturated fatty acid (PUFA) derivatives play crucial roles. However, little was known on how the insects terminate the activated immune responses after pathogen neutralization. Interestingly, C20 PUFA was detected at the early infection stage and later C18 PUFAs were induced in a lepidopteran insect, Spodoptera exigua. This study showed the role of epoxyoctadecamonoenoic acids (EpOMEs) in the immune resolution at the late infection stage to quench the excessive and unnecessary immune responses. In contrast, dihydroxy-octadecamonoenoates (DiHOMEs) were the hydrolyzed and inactive forms of EpOMEs. The hydrolysis is catalyzed by soluble epoxide hydrolase (sEH). Inhibitors specific to sEH mimicked the immunosuppression induced by EpOMEs. Furthermore, the inhibitor treatments significantly enhanced the bacterial virulence of Bacillus thuringiensis against S. exigua. This study proposes a negative control of the immune responses using EpOME/DiHOME in insects.

Diffusion of organochlorine (OCPs) and cypermethrin pesticides from rohu (Labeo rohita) internal organs to edible tissues during ice storage: a threat to human health.

The migration of organochlorine pesticides (OCPs) and cypermethrin residues from internal organs to edible tissues of ice-held Labeo rohita (rohu) was investigated in this study. The liver (246µg/kg) had the highest level of ∑OCP residues, followed by the gills (226µg/kg), intestine (167µg/kg), and muscle tissue (54µg/kg). The predominant OCPs in the liver and gut were endosulfan (53-66µg/kg), endrin (45-53µg/kg), and dichloro-diphenyl-trichloroethane (DDT; 26-35µg/kg). The ∑OCP residues in muscle increased to 152µg/kg when the entire rohu was stored in ice, but they decreased to 129µg/kg in gill tissues. On days 5 and 9, the total OCPs in the liver increased to 317µg/kg and 933µg/kg, respectively. Beyond day 5 of storage, total internal organ disintegration had led to an abnormal increase in OCP residues of liver-like mass. Despite a threefold increase in overall OCP residues by day 9, accumulation of benzene hexachloride (BHC) and heptachlor was sixfold, endrin and DDT were fourfold, aldrin was threefold, and endosulfan and cypermethrin were both twofold. Endosulfan, DDT, endrin, and heptachlor were similarly lost in the gills at a rate of 40%, while aldrin and BHC were also lost at 60 and 30%, respectively. The accumulation of OCP residues in tissues has been attributed to particular types of fatty acid derivatives. The study concluded that while pesticide diffusion to edible tissues can occur during ice storage, the levels observed were well below the allowable limit for endosulfan, endrin, and DDT.

MSR405: Inhibiting Neuroinflammation after Spinal Cord Injury in Rats.

The treatment of spinal cord injury (SCI) is often ineffective. Additionally, SCI-induced inflammation leads to secondary injury. Current anti-inflammatory hydrophilic drugs fail to reach the nerve injury site due to the blood-brain barrier. Here, we synthesized MSR405, a new lipophilic unsaturated fatty acid derivative of Radix Isatidis and investigated its therapeutic effect in SCI model rats. Furthermore, we systematically investigated its structure, toxicity, anti-inflammatory effect, and the underlying mechanism. MSR405 was injected into the abdominal cavity of the Sprague Dawley SCI model rats, and the effect on their behavioral scores and pathology was estimated to assess the status of neurological inflammation. Our data show that MSR405 treatment significantly improved the motor function of SCI rats, and markedly suppressed the associated neuroinflammation. Moreover, MSR405 could attenuate LPS-induced inflammatory response in BV2 cells (Mouse microglia cells) in vitro. Mechanistically, MSR405 inhibits proinflammatory cytokines, supporting the anti-inflammatory response. Additionally, MSR405 can significantly block the TLR4/NF-κB signaling pathway and nitric oxide production. In summary, MSR405 reduces inflammation in SCI rats through the TLR4/NF-κB signal cascade and can inhibit neuroinflammation after spinal cord injury.

Phytochemical analysis, GC-MS characterization and antioxidant activity of Hordeum vulgare seed extracts

Barley scientifically known as Hordeum vulgare (HV) is a major grain crop. Over the course of time, great interest has been developed in the usage of barley, because of its various pharmacological activities. Current study is designed to determine the chemical constituents of Hordeum vulgare (HV) seed extract by GC-MS technique, and Invitro antioxidant assays i.e. 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH) and 2-azino-bis(3-ethyl benzthiazoline-6-sulfonic acid) (ABTS) methods. GC-MS identified 16 non-polar compounds in the hexane extract of HV plant, which includes carboxylic acid (6.25%), fatty acid (37.5%), carboxylic acid amide derivative of fatty acid (6.25%), triterpinoids (18.75%), fat soluble vitamin (6.25%), phytosterol (6.25%), stigmastanes (6.25%), beta diketones (6.25%), and cycloartenol (6.25%) respectively. The major compound includes Hexadecanoic acid, methyl ester (6.84%), n-Hexadecanoic acid (8.58%), 9,12-Octadecanoic acid (Z,Z)-, Methyl Ester (8.04%), 9,12-Octadecadienoic acid (Z,Z) (57.01%), Lup-20(29)-en-3-one (3.57%), γ-Sitosterol (3.31%). Some constituents such as Lup-20(29)-en-3-one, campesterol and squalene were observed and were not previously reported. Total phenolic and total flavonoid content were determined using spectrophotometric technique and calculated as gallic acid equivalents GAE/g dry weight and rutin equivalent RE/g of dry weight respectively.The highest phenolic content exhibited by the acetone extract of HV seedsi.e. 0.0597 mg GAE/g while the highest flavonoid content exhibited by dichloromethane extract i.e. 0.09 mg RE/g and 0.25 mg QE/g of dry weight respectively. All the extracts showed significant antioxidant activity in DPPH and ABTS cation decolorization assays. Methanol and dichloromethane extract showed the highest DPPH radical scavenging activity i.e. 52.41% and 42.07% at the concentration of 100 mg/ml respectively. Moreover, the IC50 has been determined by the acetone and methanol extract of HV seeds. The high antioxidant activity of its seed extracts has made this plant pharmacologically important. Conclusively, there is a vast scope to further explore the active principals of barley so that more of its pharmacological properties can be identified.

Biological Evaluations, NMR Analyses, Molecular Modeling Studies, and Overview of the Synthesis of the Marine Natural Product (-)-Mucosin.

Natural products obtained from marine organisms continue to be a rich source of novel structural architecture and of importance in drug discovery, medicine, and health. However, the success of such endeavors depends on the exact structural elucidation and access to sufficient material, often by stereoselective total synthesis, of the isolated natural product of interest. (-)-Mucosin (1), a fatty acid derivative, previously presumed to contain a rare cis-bicyclo[4.3.0]non-3-ene moiety, has since been shown to be the trans-congener. Analytically, the fused bicyclic ring system in (-)-1 constitutes a particular challenge in order to establish its relative and absolute stereochemistry. Herein, data from biological evaluations, NMR and molecular modeling studies of (-)-1 are presented. An overview of the synthetic strategies enabling the exact structural elucidation of (-)-mucosin (1) is also presented.