Search Results (241)

Fluorite is commonly associated with calcite and other Ca-bearing gangue minerals in nature. Fluorite and its associated Ca-bearing gangue minerals share similar surface active sites involving Ca²⁺ ions and have comparable surface properties, making their flotation separation challenging. Traditional fatty acid collectors, such as oleic acid, suffer from poor selectivity. This study investigates the use of N-hydroxy-N-phenyloctanamide (HPOA) as a novel collector for fluorite, with the goal of improving its flotation separation from Ca-bearing gangue minerals. Flotation tests demonstrate that HPOA provides superior selectivity compared to oleic acid in separating fluorite from calcite. Research on the adsorption capacity of HPOA on mineral surfaces shows that, under equivalent testing conditions, HPOA shows greater adsorption amounts on fluorite than on calcite. As a result, HPOA has a superior collecting capacity in fluorite flotation. First-principles calculations reveal that HPOA adsorbs on the fluorite surface by forming chemical bonds with Ca²⁺ ions via its hydroxyl and carbonyl groups. Moreover, HPOA exhibits strong adsorption on fluorite surface, as indicated by more significant shifts in the binding energies of Ca²⁺ ions on fluorite compared to calcite after HPOA adsorption. This study highlights the potential of amide-based collectors to improve fluorite flotation and offers valuable insights into the development of more selective flotation reagents. Full article

There is an urgent need to identify interventions that broadly target aging-related cognitive decline and progression to Alzheimer’s disease (AD). Bottlenose dolphins (Tursiops truncatus) have histologic changes similar to AD in humans, and they also develop shared age-associated co-morbidities identified as risk factors for AD in humans, including type 2 diabetes, ferroptosis, and iron overload, which can be driven by nutritional C15:0 deficiency. We hypothesized that (1) dolphins would have amyloid beta (Aβ) plaques and neuroinflammation that paralleled that of humans in relation to age-related progression, quantitative concentration, and brain region; and (2) C15:0 would have dose-dependent activities relevant to protecting cognitive health. Quantitative immunohistochemistry staining was used to assess 68 tissues from archived brains of 19 Navy dolphins to evaluate associations among amyloid beta (Aβ) plaques and neuroinflammation by brain region, sex, and age group. Further, dose-dependent C15:0 activities, using a third-party panel intended to screen for potential AD therapeutics, were evaluated. Similar to humans, dolphins had the highest Aβ plaque density variation in the hippocampus (90th percentile of 4.95 plaques/mm²), where plaque density increased with age (p = 0.05). All measured markers of neuroinflammation were detected, including the highest concentrations of activated microglia (CD68⁺) in the hippocampus (0.46 ± 0.38 cells/mm²). C15:0 was a dose-dependent inhibitor of two targets, fatty acid amide hydrolase (FAAH) (IC₅₀ 2.5 µM, 89% maximum inhibition at 50 µM relative to URB597) and monoamine oxidase B (MAO-B) (IC₅₀ 19.4 µM, 70% maximum inhibition at 50 µM relative to R(-)-Deprenyl). These activities have demonstrated efficacy against Aβ formation and neuroinflammation, including protection of cognitive function in the hippocampus. These findings suggest that, in addition to protecting against AD co-morbidities, C15:0 may play a distinct role in supporting cognitive health, especially at higher concentrations. Full article

The endocannabinoid system (ECS) plays a crucial role in maintaining homeostasis by regulating immune response, energy metabolism, cognitive functions, and neuronal activity. It consists of endocannabinoids (eCBs), cannabinoid receptors (CBRs), and enzymes involved in eCB biosynthesis and degradation. Increasing evidence highlights the involvement of the ECS under several pathological conditions, making it a promising therapeutic target. Recent research efforts have focused on modulating endogenous eCB levels, particularly through the inhibition of fatty acid amide hydrolase (FAAH), the main catabolic enzyme of the major eCB anandamide. Natural substances, including plant extracts and purified compounds, can inhibit FAAH and represent a promising area of pharmacological research. Natural FAAH inhibitors are particularly attractive due to their potentially lower toxicity compared to synthetic compounds, making them safer candidates for therapeutic applications. Phytocannabinoids, flavonoids, and flavolignans have been shown to efficiently inhibit FAAH. The structural diversity and bioactivity of these natural substances provide a valuable alternative to synthetic inhibitors, and may open new avenues for developing innovative pharmacological tools. Full article

Candidiasis belongs to common fungal infections and is usually mild and self-limiting. However, in patients with immunodeficiencies, it can transform into invasive infections with high mortality. Long-term antifungal treatment can lead to the emergence of resistance. The problem is further complicated by the development of fungal biofilm resistant to conventional antimicrobials. Due to a limited choice of available antifungals, the development of novel active agents, such as antimicrobial peptides (AMPs), is highly desirable. Human cathelicidin LL-37 is an intensively studied AMP with a confirmed broad spectrum of antimicrobial activities. Due to the relatively high costs of production, the design of shorter analogs of LL-37 has been recommended. In this study, we synthesized a KR12 amide, KRIVQRIKDFLR-NH₂, and its 24 derivatives obtained by substitution with fatty acids. The compounds were tested for their antifungal potential. They exhibited activity against the Candida albicans, C. glabrata, C. tropicalis and C. lipolytica. Five compounds: C₁₀-KR12-NH₂, C₁₂-KR12-NH₂, C₁₄-KR12-NH₂, 2-butyloctanoic acid-KR12-NH₂, and 4-phenylbenzoic acid-KR12-NH₂ were highly active against planktonic cells. C₁₄-KR12-NH₂ demonstrated also activity against C. albicans biofilm cultured on polystyrene for 24, 48 and 72 h. Lipidation has proven to be an effective strategy for improving microbiological activity of the KR12-NH₂ peptide. Full article

Essential amino acids and essential fatty acids are vital nutrients that must be obtained from the diet. However, traditional sources face limitations amid increasing global food security and sustainability challenges. This study aims to evaluate the nutritional potential of novel foods, including microalgae (e.g., spirulina and chlorella), fungi (e.g., oyster and shiitake mushrooms), edible insects (e.g., mealworms and migratory locusts), and unconventional plants (e.g., water lentils and canihua). The study will compare their amino acid and fatty acid profiles with those of conventional animal and plant sources. The comparative analysis conducted in this study reveals that these innovative foods offer balanced and high-quality protein and lipid profiles, and contribute essential nutrients needed to prevent deficiencies and support metabolic health. Significantly, the integration of these novel foods into established dietary patterns, such as the Mediterranean diet, has the potential to enhance nutritional quality while promoting environmental sustainability. In conclusion, the adoption of these innovative food sources provides a viable strategy to meet nutritional demands and address global health and ecological challenges, paving the way toward a more resilient and sustainable food system. Full article

Nineteen potential mimics of 8,9-epoxyeicosatrienoic acid (8,9-EET), a natural bioactive oxylipin, were synthesized and evaluated for their ability to protect renal mesangial cells against sorafenib-induced cell death in a water-soluble tetrazolium (WST-8) assay. All compounds were also evaluated as inhibitors of soluble epoxide hydrolase. As expected of a potent pan-kinase inhibitor the drug sorafenib caused a significant decrease in cell viability in HRMCs. Several analogs containing amide and oxamide groups in place of the epoxide showed efficacy in reducing sorafenib induced human renal mesangial cell (HRMC) death. Oxamide containing analogs proved particularly effective, with the most promising analog increasing cell viability five-fold over control at 1 µM. These analogs, containing an oxamide group as a bioisostere for the epoxide in 8,9-EET, did not display significant inhibitory activity towards soluble epoxide hydrolase. This preliminary structure–activity relationship analysis reveals the oxamide group as a promising bioisostere for the epoxide in the 8,9-position of the fatty acid chain, producing protective effects against sorafenib-induced cell death in HRMCs. Collectively, these findings demonstrate the potential for using epoxide mimics and particularly oxamides as 8,9-EET analogs as bioisosteres of the corresponding epoxide in a therapeutic strategy against sorafenib-induced glomerular nephrotoxicity. Full article

Background and aims: Aframomum melegueta (A. melegueta) from the ginger family is appreciated for its pungent seeds widely used in African ethno-medicine. Among the several biological activities associated with the seed’s preparations, some preclinical studies suggest a set of neuroactive properties that have not been tested in humans to date. We performed a clinical trial to investigate the effects of A. melegueta seed extracts on anxiety, stress, mood, and sleep in healthy subjects with moderate anxiety levels. In vitro pharmacological assays targeting the endocannabinoid, serotoninergic, and GABAergic systems were conducted to elucidate the underlying mechanism of action. Methods: A. melegueta standardized to 10% total vanilloids (primarily 6-gingerol, 6-shogaol, and 6-paradol) was obtained after hydroalcoholic extraction and the spray-drying microencapsulation process. Subjects consumed 50, 100, or 150 mg of the extract daily for three days. A set of validated psychometric test questionnaires was collected before and 48 h after the first intake. A. melegueta extract interaction with canonical endocannabinoid receptors (hCB1R and hCB2R), the serotonin receptor (5HT1AR) and gamma-aminobutyric acid receptor (GABAA1R) was evaluated by the radioligand binding assay. Additionally, receptor functional assays and enzyme inhibition assays were conducted to test the extract’s functional activity on the non-canonical endocannabinoid receptor (TRPV1) and the cannabinoid fatty-acid amide hydrolase enzyme (FAAH), respectively. Results: In vitro pharmacological tests showed that the A. melegueta extract activated TRPV1, modulated both hCB2R and 5HT1AR and inhibited FAAH, which is the enzyme primarily responsible for hydrolyzing endogenous anandamide. After a 48 h intake period, the extract significantly reduced anxiety and tension related to stress, improved overall mood, and enhanced sleep quality in the participants at doses ranging from 50 to 150 mg, with no reported side effects. Conclusions: This study supports the potential of the A. melegueta extract for anxiety reduction, mood improvement, stress mitigation, and sleep enhancement. The in vitro tests suggest that the extract’s primary mechanism of action may involve the inhibition of FAAH, which is a key target in anxiety management. Full article

Annatto (Bixa orellana L.) is cultivated primarily for the extraction of bixin, a natural dye with substantial industrial importance, resulting in the generation of large quantities of residues that remain underutilized. This study provides the first in-depth characterization of annatto byproducts derived through molecular distillation, highlighting their untapped potential for sustainable innovation. Employing state-of-the-art techniques—HS-SPME-GC-MS for volatile compounds and UPLC-MS/QTOF for non-volatile ones—the research identified a remarkable array of bioactive constituents. Over thirty pharmacologically significant compounds were unveiled, many appearing for the first time in annatto byproducts. Notable discoveries include diterpenoid alcohols, oleamide, δ-tocotrienol, n-alkanes, fatty acid methyl esters, and springene among the volatiles. Among the non-volatiles, groundbreaking identifications such as dihydroactinidiolide, dihydrochalcone, 3-phenyl propiofenone, novel tetracosan amides, halisphingosine A, kauranetriols, and phytoene derivatives redefine the chemical profile of this residue. Further amplifying the value of these findings, the study successfully transformed these byproducts into innovative antioxidant packaging materials, demonstrating their high potential for food preservation and sustainable applications. The packaging films, developed from samples devoid of vegetable oil, exhibited robust antioxidant properties, offering a compelling solution to extend shelf life and reduce spoilage. This work underscores the importance of revalorizing agricultural residues like annatto byproducts, turning waste into high-value resources that align with the principles of the circular economy. Full article

Background: The endocannabinoid system (ECS) is one of the most important systems modulating functions in the body. The ECS, via cannabinoid (CB: CB1 and CB2) receptors, endocannabinoids occurring in the brain (e.g., anandamide (AEA) and 2-arachidonoylglycerol (2-AG)) and enzymes degrading endocannabinoids in the brain (fatty-acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL)), plays a key role in the regulation of mood and anxiety. However, the effects of cannabinoid compounds on anxiety-related responses are complex and yield mixed results depending on the type of pharmacological manipulation (direct or indirect) of functions of the ECS, as well as the kinds of cannabinoids, dosage and procedure. Methods: The aim of this study was to determine and compare the influence of the direct (via CB receptors ligands) and indirect (via inhibition of enzymes degrading endocannabinoids in the brain) pharmacological modulation of ECS function on anxiety-like responses in mice in the elevated plus maze (EPM) test. For this purpose, in the first step of the experiments, we used selected ligands of CB1, CB1/CB2 and CB2 receptors to assess which types of CB receptors are involved in anxiety-related responses in mice. Next, we used inhibitors of FAAH (which breaks down AEA) or MAGL (which breaks down 2-AG) to assess which endocannabinoid is more responsible for anxiety-related behavior in mice. Results: The results of our presented research showed that an acute administration of CB1 receptor agonist oleamide (5–20 mg/kg) had no influence on anxiety-related responses and CB1 receptor antagonist AM 251 (0.25–3 mg/kg) had anxiogenic effects in the EPM test in mice. In turn, an acute administration of mixed CB1/CB2 receptor agonist WIN55,212-2 used at a dose of 1 mg/kg had an anxiolytic effect observed in mice in the EPM test. What is of interest is that both the acute administration of a CB2 receptor agonist (JWH 133 at the doses of 1 and 2 mg/kg) and antagonist (AM 630 at the doses of 0.5–2 mg/kg) had anxiogenic effects in this procedure. Moreover, we revealed that an acute administration of only FAAH inhibitor URB 597 (0.3 mg/kg) had an anxiolytic effect, while MAGL inhibitor JZL 184 (at any used doses (2–40 mg/kg)) after an acute injection had no influence on anxiety behavior in mice, as observed in the EPM test. Conclusions: In our experiments, we confirmed the clearly significant involvement of the ECS in anxiety-related responses. In particular, the pharmacological indirect manipulation of ECS functions is able to elicit promising anxiolytic effects. Therefore, the ECS could be a potential target for novel anxiolytic drugs; however, further studies are needed. Full article

Background: Fatty acids (FAs) represent a ubiquitous class of nonpolar alkyl carboxylate metabolites with diverse biological functions. Nutrition, metabolism, and endogenous and exogenous stress influence the overall FA metabolic status and transport via the bloodstream. FAs esterified in lipids are of particular interest, as they represent promising biomarkers of pathological diseases and nutritional status. Methods: Here, we report a validated gas chromatographic-mass spectrometric (GC-MS) method for the quantitative analysis of 32 FAs exclusively bound in esterified lipids. The developed sample preparation protocol comprises three steps using only 5 µL of human serum for Folch extraction, sodium methoxide-catalyzed transesterification in tert-butyl methyl ether, and re-extraction in isooctane prior to a quantitative GC-MS analysis with positive ion chemical ionization (PICI) and selected ion monitoring (SIM). Results: The base-catalyzed transmethylation step was studied for 14 lipid classes and was found to be efficient under mild conditions for all major esterified lipids but not for free FAs, lipid amides, or sphingolipids. To minimize matrix effects and instrument bias, internal fatty acid trideuteromethyl esters (D3-FAME) standards were prepared through isotope-coded derivatization with D3-labeled methylchloroformate/methanol medium mixed with each transmethylated serum extract for the assay. The method was validated according to FDA guidelines and evaluated by analyzing NIST SRM 2378 Serum 1 and sera from three healthy donors. Conclusions: The measured quantitative FA values are consistent with the reference data of SRM 2378, and they demonstrate the application potential of the described method for general FA analysis in esterified lipids as a novel complementary tool for lipidomics, as well as for the analysis of membrane FAs in dry blood spots and red blood cells. Full article

Ipomoeassin F (Ipom-F) is a plant-derived macrocyclic resin glycoside that potently inhibits cancer cell growth through blockage of Sec61-mediated protein translocation at the endoplasmic reticulum. Recently, detailed structural information on how Ipom-F binds to Sec61α was obtained using Cryo-EM, which discovered that polar interactions between asparagine-300 (N300) in Sec61α and four oxygens in Ipom-F are crucial. One of the four oxygens is from the carbonyl group at C-4 of the fatty acid chain. In contrast, our previous structure–activity relationship (SAR) studies suggest that the carbonyl group is not essential. To resolve this discrepancy, we designed and synthesized two new open-chain analogues (10 and 11); 10 without the C-4 carbonyl had a dramatic activity loss, whereas 11 with an amide functional group was even more potent than Ipom-F. These new SAR data, in conjunction with some previous SAR information, imply two functional roles of the C-4 carbonyl: (1) to form H-bonds with N300; and (2) to regulate interactions of the fatty acid chain with membrane lipids. Impacts of these dual functions on antiproliferation depend on the overall structure of an Ipom-F derivative. Moreover, 11 can serve as a lead compound for developing future amino acid/peptide-modified analogues of Ipom-F with improved therapeutic properties. Full article

To ensure food security amid dwindling natural resources, alternative proteins (APs) have been suggested as a sustainable solution. Yet, the adoption and consumption of APs remain limited. This review aims to delve into the latest progress (following PRISMA guidelines) concerning the utilization of proteins from alternative sources, particularly focusing on their effective incorporation into food products. Our findings reveal that insect proteins can improve amino acid profiles in bakery products. However, consumer acceptance remains low due to cultural biases, with optimal sensory results being achieved at lower substitution levels (5–10%). Mushroom proteins, when incorporated into meat analogs and bakery items, enhance nutritional value and offer favorable sensory properties, making them viable replacements in meat products. Plant-based proteins, such as pea and soy proteins, increase fiber and antioxidants and improve texture in meat alternatives, although formulation adjustments are necessary to meet consumer expectations for taste and overall experience. Microalgae offer unique benefits for bakery, confectionery, and dairy products by boosting protein, fatty acids, and probiotic growth while maintaining sensory acceptability. In conclusion, this study highlights that the effective incorporation of APs into food products can help in the development of healthier, more sustainable diets. That said, the success of AP acceptance will depend on continued innovations in formulation and consumer education. Full article

This study investigates the multifunctional potential of horse oil fermented with barley nuruk, a traditional fermentation starter, focusing on its α-glucosidase inhibitory activity and bioactive applicability. Gas chromatography–tandem mass spectrometry (GC-MS/MS) revealed significant changes in fatty acid composition during fermentation, with oleic acid amide and palmitic acid amide remaining stable and stearic acid amide forming prominently by day 10. Molecular docking demonstrated that the amide structures play a key role in α-glucosidase inhibition through essential hydrogen bonding interactions. Next-generation sequencing (NGS) analysis showed a notable reduction in pathogenic bacteria, such as Salmonella enterica, and a dominance of Lactobacillus acidophilus (95.2%) by day 10. The α-glucosidase inhibitory activity increased progressively with fermentation, with the day 10 extract surpassing the synthetic inhibitor acarbose, highlighting its potential for diabetes management. A human skin primary irritation test confirmed the hypoallergenic nature of both hexane-extracted and fermented horse oil products, ensuring their safety for topical applications. In conclusion, fermented horse oil demonstrates significant α-glucosidase inhibitory activity and proven safety, positioning it as a promising natural resource for therapeutic and functional product development. Further studies are needed for clinical validation and commercialization in diabetes management and related applications. Full article

Despite the potential benefits of cannabidiol as a skin-soothing ingredient, its regulatory status hampers its general use in cosmetic products in many countries. To develop an alternative to cannabidiol, fatty acid amide molecules mimicking the chemical structure of endocannabinoids were manufactured using a lipase-catalyzed process. A mixture of fatty acid amides from sunflower oil and 1-amino propan-3-ol was synthesized using an immobilized lipase reaction, and the activation of cannabinoid receptor 1 (CB1R) was measured using a cAMP assay. The anti-inflammatory activity of the endocannabimimetic ingredients was evaluated in cultured human monocytes and ex vivo human skin explant models. A clinical study was conducted to address the skin hydration, skin barrier function, and skin redness, and the ratio of the interleukin-1-receptor antagonist (IL1-RA) to IL-1α in corneocytes, as a marker for skin sensitivity, were also measured. As a result, the activation of CB1R by endocannabimimetic ingredients was observed in cAMP assays, and a reduction in inflammatory responses by human monocytes induced by lipopolysaccharide treatment were also observed. External stress-induced inflammatory responses were reduced in ex vivo human skin explants. Improvements in skin hydration and barrier function were observed in a clinical study. A significant decrease in skin redness and the IL-1RA to IL-1α ratio was also observed. Endocannabimimetic ingredients, as alternatives to cannabidiol, can be used in skin-soothing cosmetics to increase skin hydration, improve skin barrier function, and reduce skin sensitivity. Full article

(1) Background: Carbapenem-resistant Acinetobacter baumannii (CBRAB) and Pseudomonas aeruginosa (CBRPA) are critical and high-priority pathogens that require new therapeutic developments. Medicinal plants are valuable pharmaceutical resources. This study explored the anti-infective properties of Mayan plants, Bignonia potosina, and Thouinia paucidentata. (2) Methods: Plant parts were extracted using n-hexane, and their ability to inhibit bacterial growth and counteract resistance mechanisms and virulence factors in CBRAB and CBRPA was assessed. GC-MS analysis of the composition of the non-polar extracts and chemometric techniques correlated the phytoconstituents with anti-infective properties. (3) Results: Bignonia potosina liana and flower extracts exhibited potent antibacterial activity against A. baumannii strains (MIC 15.7 to 250 µg/mL) and moderate activity against P. aeruginosa strains (MIC 250 to 1000 µg/mL). Thouinia paucidentata leaf extract at 1000 µg/mL reduced imipenem MIC by 2048-fold for CBRAB, and B. potosina flower extract significantly inhibited A. baumannii catalase activity (at 62.5 µg/mL) and reduced P. aeruginosa pyocyanin production (at 1000 µg/mL). Chemometric analysis identified fatty acids, fatty acid amides, terpenes, and higher alkanes as contributors to their anti-infective properties. (4) Conclusions: This study highlights the potential of medicinal plants in the development of novel anti-infective therapies against CBRAB and CBRPA with various targets. Full article