Search Results (143)

Long-chain fatty acids (LCFAs) have emerged as important regulators of cancer metabolism, but their impact on hormone receptor expression in breast cancer (BCA) remains poorly understood. In this study, we investigated the effects of five LCFAs—linoleic acid (LA), oleic acid (OA), elaidic acid (EA), palmitic acid (PA), and α-linolenic acid (LNA)—on two BCA cell lines: luminal-type MCF7 and triple-negative MDA-MB-231 (MB231). All LCFAs suppressed cell viability and mitochondrial function in a dose-dependent manner, accompanied by decreased membrane potential, increased reactive oxygen species production, and a metabolic shift. Notably, OA reduced both mRNA and nuclear protein levels of estrogen receptor alpha (ERα) in MCF7 cells, leading to impaired responses to estradiol and tamoxifen. In contrast, PA induced nuclear ERα expression in MB231 cells, although ER signaling remained inactive. MicroRNA profiling revealed that OA upregulated ER-suppressive miR-22 and miR-221 in MCF7, while PA increased miR-34a in MB231, contributing to ERα induction. These findings suggest that specific LCFAs modulate ER expression through epigenetic and post-transcriptional mechanisms, altering hormonal responsiveness in BCA. Our results offer new insights into how dietary lipids may influence therapeutic efficacy and tumor behavior by regulating nuclear receptor signaling. Full article

The technology of fucoidan extraction significantly affects its properties. This study aimed to evaluate the impact of dynamic maceration (DM) and ultrasound-assisted extraction (UAE) on the antioxidant and anticancer properties of fucoidan from Arctic brown algae. Fucus vesiculosus (Fv), Fucus serratus (Fs), Fucus distichus (Fd), and Ascophyllum nodosum (An) were collected from the Barents Sea. The average yield of fucoidan and uronic acid was higher (by 43.2% and 22.0%, respectively) after UAE, while phlorotannin content decreased by 53.7% compared with DM. The fucose level for all algae increased after UAE, while the molecular weight of fucoidans was lower. The highest antioxidant activity was noted for the fucoidan from An and Fv, which were obtained by DM and can be associated with the high concentrations of phlorotannins. The treatment of HeLa G-63 cells with all studied fucoidans for 48 h increased concentration-dependently the number of dead cells. The most promising were Fv and Fs fucoidans with high phlorotannins, low sulfates, and uronic acid extracted by DM. The co-administration of paclitaxel and fucoidan caused cell cycle arrest in the G2/M phase. The calculated for the first time combinatory effect showed that the simultaneous use of paclitaxel and fucoidan exposure leads to a synergistic interaction. Our results support the rationality of fucoidan use in complex chemotherapy to improve survival, quality of life and immunity in patients with cervical carcinoma. Full article

Lysosomes are important acidic subcellular organelles whose dysfunction can lead to some related diseases. The development of new lysosome-imaging-guided AIEgens for the photodynamic therapy of cancer cells is important. In this work, two novel organic compounds with AIE characteristics, namely, TPAB-CF₃ and TPAB-diCF₃, were designed and synthesized by introducing the weakly basic morpholinyl moiety with lysosome-targeting ability into a triphenylamine-based luminogen. The distorted spatial feature of TPA and the D₁-D₂-π-A structure of these AIEgens prevented the aggregation-caused quenching of traditional fluorescent molecules and efficiently promoted the separation of the HOMO and LUMO. The outcomes were AIE features and a narrow single-triplet energy gap. Furthermore, TPAB-CF₃ and TPAB-diCF₃ showed bright yellow fluorescence emission peaks at 577 and 601 nm; large Stokes shifts of 234 and 256 nm, respectively; and excellent lysosome-targeted imaging of HeLa cells (Pearson’s coefficient = 0.90). In addition to the good ¹O₂-generation ability under light irradiation, these AIEgens achieved the high-efficiency bright lysosome imaging-guided photodynamic killing of cancer cells under white-light irradiation. Full article

Background/Objectives: Glaucoma is the leading cause of irreversible blindness worldwide and oxidative stress is considered to play a key role in its development. While antioxidants offer a promising approach to mitigating oxidative stress, their clinical application is often hindered by bioavailability and absorption challenges. Entrapment antioxidants within liposomes may overcome these issues, enhancing their stability and delivery. The aim of this study was to develop a novel composite liposomal formulation for glaucoma treatment, designed to enhance lipoic acid bioavailability and administration through its incorporation into the lipid bilayer. Methods: Liposomes were prepared via lipid film hydration and extrusion. To characterize them, the following analyses were performed: FTIR spectroscopy, liposomal bilayer melting temperature (Tm), TEM, DLS, Z-potential, antioxidant activity, and cytotoxicity assays. Results: The efficient incorporation of lipoic acid into the liposomes’ lipid bilayer was confirmed by FTIR. This incorporation resulted in an increase in the Tm, from 37.0 °C for liposomes to 40.0 °C for liposomes with lipoic acid (L-LA). TEM images confirmed that the spherical morphology of the lipid vesicles remained unchanged following LA incorporation. Dynamic Light Scattering analysis revealed effective diameters of 423 ± 36 nm for L liposomes and 404 ± 62 nm for L-LA liposomes. Notably, the Z-potential shifted from +4.7 ± 0.4 mV (L) to −0.4 ± 0.3 mV (L-LA). Furthermore, L-LA exhibited significant antioxidant activity (31.6 ± 0.4%) compared with L (5.3 ± 0.3%) and biocompatibility, suggesting its potential for therapeutic applications. Conclusions: In summary, biocompatible composite liposomes with antioxidant capacity were successfully developed, resulting in promising candidates for neuroprotective glaucoma therapy. Full article

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, with growing concerns about the impact of omega-6 polyunsaturated fatty acids (n-6 PUFAs) on cardiovascular health. This study aims to evaluate the relationship between serum linoleic acid (LA) levels and waist-to-height ratio (WHtR), a recognized cardiovascular risk marker, in children. The research was conducted in two parts. First, a global analysis of publicly available data (2019–2021) explored the association between nutritional factors and CVD prevalence across 183 countries. Second, a cross-sectional study involving 67 children (33 with obesity and 34 with healthy weight, classified using BMI Z-scores) examined the correlation between serum LA levels and WHtR. Global analysis revealed a moderate correlation between low seafood omega-3 fatty acid intake and CVD incidence (rho = 0.341), while low polyunsaturated fatty acid consumption showed a weak correlation (rho = 0.228). In children, a significant positive correlation was observed between serum LA levels and WHtR (rho = 0.716, p < 0.001), with similar correlations found when stratified by sex (girls: rho = 0.690; boys: rho = 0.709). Serum LA levels also correlated positively with weight (rho = 0.684). These findings are consistent with the existing literature, that high serum LA levels may contribute to early cardiometabolic risk in children, emphasizing the need for dietary interventions to mitigate cardiovascular risks in early life. Full article

Blue mold caused by Penicillium italicum (P. italicum) is a major postharvest disease in citrus fruits. Lipoic acid (LA) is a potent antioxidant with biological activity that was evaluated for its inhibitory effects on P. italicum and citrus blue mold using in vitro and in vivo experiments. The results demonstrated that LA effectively suppressed the mycelial growth and spore germination of P. italicum. LA increased hydrogen peroxide levels, compromising cell membrane integrity and leading to enhanced membrane permeability, as indicated by the increased relative conductivity and decreased protein and total sugar contents in P. italicum mycelia. Furthermore, LA delayed disease progression in citrus fruits infected with P. italicum through increasing total phenol and flavonoid contents and enhancing the activities of phenylalanine ammonia lyase, polyphenol oxidase, superoxide dismutase, and peroxidase in citrus peel. Overall, LA exhibited strong antifungal activity against P. italicum and improved citrus fruit resistance to blue mold, highlighting its potential as a natural postharvest disease control agent. Full article

The Yidun island arc was formed in response to the Late Triassic westward subduction of the Ganzi–Litang oceanic plate, a branch of the Paleo-Tethys Ocean. The Zhongdian arc, located in the south of the Yidun island arc, has relatively large number of porphyry (skarn) type Cu–Mo ± Au polymetallic deposits, the largest of which is the Pulang Cu (–Mo–Au) deposit with proven Cu reserves of 5.11 Mt, Au reserves of 113 t, and 0.17 Mt of molybdenum. However, the relationship between mineralization and the potassic alteration zone, phyllic zone, and propylitic zone of the Pulang porphyry deposit is still controversial and needs further study. Titanite (CaTiSiO₅) is a common accessory mineral in acidic, intermediate, and alkaline igneous rocks. It is widely developed in various types of metamorphic rocks, hydrothermally altered rocks, and a few sedimentary rocks. It is a dominant Mo-bearing phase in igneous rocks and contains abundant rare earth elements and high-field-strength elements. As an effective geochronometer, thermobarometer, oxybarometer, and metallogenic potential indicator mineral, titanite is ideal to reveal the magmatic–hydrothermal evolution and the mechanism of metal enrichment and precipitation. In this paper, major and trace element contents of the titanite grains from different alteration zones were obtained using electron probe microanalysis (EPMA) and laser-ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to define the changes in physicochemical conditions and the behavior of these elements during the process of hydrothermal alteration at Pulang. Titanite in the potassic alteration zone is usually shaped like an envelope. It occurs discretely or is enclosed by feldspar, with lower contents of CaO, Al, Sr, Zr and Hf; a low Nb/Ta ratio; high ∑REE + Y, U, Th, Ta, Nb, and Ga content; and high FeO/Al₂O₃ and LREE/HREE ratios. This is consistent with the characteristics of magmatic titanite from fresh quartz monzonite porphyry in Pulang and other porphyry Cu deposits. Titanite in the potassium silicate alteration zone has more negative Eu anomaly and a higher U content and Th/U ratio, indicating that the oxygen fugacity decreased during the transformation to phyllic alteration and propylitic alteration in Pulang. High oxygen fugacity is favorable for the enrichment of copper, gold, and other metallogenic elements. Therefore, the enrichment of copper is more closely related to the potassium silicate alteration. The molybdenum content of titanite in the potassium silicate alteration zone is 10²–10⁴ times that of the phyllic alteration zone and propylitic alteration zone, while the copper content is indistinctive, indicating that molybdenum was dissolved into the fluid or deposited in the form of sulfide before the medium- to low-temperature hydrothermal alteration, which may lead to the further separation and deposition of copper and molybdenum. Full article

Lanthanum (La) is often used in industry and agriculture, leading to its accumulation in natural environments and potential ecological risks. The objective of this study was to examine the effects on the growth, metabolism, and nutrient composition of Brassica rapa exposed to at low (1 µM), medium (1 mM), and high (10 mM) La concentrations. We used chemical analytical, molecular, and metabolomic methods and found that high La exposure induced a hormetic effect, triggering both stimulatory and inhibitory responses. La reduced aluminum (Al), cobalt (Co), nickel (Ni), and chromium (Cr) levels at all concentrations, while medium and high doses also decreased phosphorus (P) and iron (Fe). La accumulation in B. rapa increased with La levels, affecting metabolic processes by modulating reactive oxygen species (ROS), increasing proline, and reducing total polyphenol content. Flavonoid levels were altered, chlorophyll and carotenoids declined, and non-photochemical quenching increased. Gene expressions related to flavonoid, carotenoid, and chlorophyll metabolism, as well as ion transport, exhibited a dose-dependent modulation. On the contrary, fatty acid composition remained unaffected. Our results indicate that La accumulates in in B. rapa and disrupts the plant metabolism. Despite an evident effect on plant productivity, our results also raise concerns about the potential health risks of consuming La-enriched B. rapa plants. Full article

Facial thread lifting with absorbable threads such as poly(L-lactide-co-ε-caprolactone) (P(LA/CL)) has been explored in an animal model. This experimental study utilized P(LA/CL)-HA-micro threads enhanced with hyaluronic acid microencapsulation via NAMICA technology in five four-month-old female pigs. The effects were compared to those of P(LA/CL)-HA threads over a six-month period through histological analysis. The results indicated improvements in skin remodeling, with P(LA/CL)-HA-micro threads enabling controlled and prolonged release of hyaluronic acid, leading to sustained improvements in tissue structure. These findings suggest that microencapsulated threads could enhance therapeutic outcomes; however, these results are preliminary and derived from an animal model. Further research and clinical trials are necessary to confirm these benefits in human subjects. Full article

The two-stage process for the treatment of rare earth phosphate minerals, involving an oxalic acid conversion leach and subsequent EDTA dissolution, has been demonstrated as a promising alternative to conventional extraction methods. To underpin a more detailed understanding, this work serves to further develop knowledge of the linkage between the stages and key practical aspects of the operation of the EDTA dissolution. A more detailed treatment of the phenomena observed in the EDTA treatment, characteristics of the solids, mass loss in dissolution, and the impact of parameter alterations in both stages provide greater holistic knowledge of the proposed flowsheet and considerations that will need to be addressed when increasing scale. Acid production (indicated by a pH decrease) in the EDTA dissolution stage was shown to be a feature of the reaction and not of residual acid associated with the solids from the oxalic acid stage. The consistency with which the rare earths were dissolved with respect to the phosphorus provided greater confidence that Nd and Pr (greater dissolution than P) are recovered at a higher efficiency than Ce and La (poorer dissolution than P). This was only not the case at high solids loading across both tests, leading to both oxalate and EDTA-deficient systems, respectively. Under high conversion conditions, it was demonstrated that Nd and Pr recoveries into solution approaching 70% were achieved. This equated to in excess of 17 gL⁻¹ of total rare earths in solution. Solid/liquid separation was shown to be a significant challenge, created by both the fine particle size distribution of the leached residue and the dispersant nature of EDTA. Full article

Targeting DNA damage response (DDR) pathways represents one of the principal approaches in cancer therapy. However, defects in DDR mechanisms, exhibited by various tumors, can also promote tumor progression and resistance to therapy, negatively impacting patient survival. Therefore, identifying new molecules from natural extracts could provide a powerful source of novel compounds for cancer treatment strategies. In this context, we investigated the role of oleanolic acid (OA), identified in fermented Aglianico red grape pomace, in modulating the DDR in response to camptothecin (CPT), an inhibitor of topoisomerase I. Specifically, we found that OA can influence the choice of DNA repair pathway upon CPT treatment, shifting the repair process from homologous recombination gene conversion to single-strand annealing. Moreover, our data demonstrate that combining sub-lethal concentrations of OA with CPT enhances the efficacy of topoisomerase I inhibition compared to CPT alone. Overall, these findings highlight a new role for OA in the DDR, leading to a more mutagenic DNA repair pathway and increased sensitivity in the HeLa cancer cell line. Full article

With an output of more than two million tons of alumina per year, Venezuela is an important producer. As observed, this mining extraction activity generates a large number of by-products poorly valorized for many reasons (economic, technical, and due to environmental standards and regulations) Venezuela production generates wastes (more than 15 million of m³) called red muds, which are dumped in old lagoons near the Orinoco river or stored. This sludge has a high alkalinity (pH between 10 and 13) and a chemical composition containing some heavy metals (40 ppm Cr, 107 ppm La, 178 ppm Ce) that means it is considered environmentally problematic waste. However, their mineralogical, textural and structural characteristics make them adsorption materials. So, the aim of the study presented here was to investigate the sorption properties of these residues in the case of treatment of water from acid mine drainage. In fact, with an important reactive surface, their capacities to trap by adsorption trace elements such as cadmium, lead or zinc has been studied. Batch sorption tests revealed significant retention of contaminants such as Pb, Zn and As. These retention processes were interpreted using the Langmuir isotherm model. The promising first results indicate that the red mud named Venezuelan bauxite residue (VBR) reveals its great potential as a sorbent of inorganic pollutants. The sorption process is chemically dependent and efficient for certain pH and IS ranges. In addition, the material showed a strong affinity for the adsorption of arsenate (As⁵⁺). This was observed during post adsorption chemical speciation experiments, through the very high affinity of this element for the least mobile fractions, including oxyhydroxides mobile fractions, including Fe oxyhydroxides (amorphous). Nevertheless, these mining by-products could be considered as valuable absorbent materials. Despite this promising results, further studies are required to evaluate their potential in different conditions (dynamic tests, pH, IS, inorganic and organic contaminants, concentration and time effect). Full article

Background/Objectives: Cytolytic vaginosis or, classically, Doderlein’s cytolysis is characterized by significant growth of species of the Lactobacillus genus, which leads to high amounts of lactic acid in the vaginal environment. Lactobacillus crispatus has been proposed as a key pathogen in this clinical condition. The symptomatology of cytolytic vaginosis is commonly confused with that of vulvovaginal candidosis, leading to inadequate and ineffective azole therapies. Nevertheless, historically, the use of sodium bicarbonate intimate baths was an effective way to reduce the symptoms of cytolytic vaginosis. Methods: In this study, four HPMC gel prototypes were developed, containing sodium bicarbonate concentrations ranging from 4% to 7% (w/w). These gels were evaluated for their physicochemical properties, antimicrobial activity, interference with lactobacilli adhering to cells, and cellular and tissue biocompatibility. Results: The gels presented pH values of around 9.0, and osmolality between 706 mOsm/kg (F4) and 1065 mOsm/kg (F7). The viscosity upon heating to physiologic temperature and dilution with simulated vaginal fluid was highly affected by the concentration of sodium bicarbonate. Gels with higher sodium bicarbonate concentrations (F6 and F7) were not shown to be stable in these conditions. All formulations exhibited effective antimicrobial activity against seven L. crispatus strains, with MIC values ranging from 6.25% to 25% (v/v) in terms of dilution. Additionally, the 4% (w/w) gel significantly interfered with the adhesion of L. crispatus to epithelial cells in competition and exclusion assays, reducing adhesion by more than 90% in relation to the control. Cytotoxicity tests on the Hec-1A, HeLa, and VK2/E6E7 cell lines indicated that the F4 and F5 gels demonstrated lower cytotoxicity levels compared to those with higher concentrations. Furthermore, ex vivo assays using porcine vaginal tissue confirmed that the 4% gel was non-toxic at a 25% (v/v) dilution. Conclusions: Based on these results, the 4% (w/w) sodium bicarbonate gel (F4) emerges as a promising therapeutic option for cytolytic vaginosis, offering effective bacterial interference, favourable physicochemical properties, and biocompatibility suitable for vaginal application. Full article

Acidic stress is a formidable environmental factor that exerts adverse effects on plant growth and development, ultimately leading to a potential reduction in agricultural productivity. A low pH triggers Ca²⁺ influx across the plasma membrane (PM), eliciting distinct responses under various acidic pH levels. However, the underlying mechanisms by which Arabidopsis plant cells generate stimulus-specific Ca²⁺ signals in response to acidic stress remain largely unexplored. The experimentally induced stimulus may elicit spikes in cytosolic free Ca²⁺ concentration ([Ca²⁺]_i) spikes or complex [Ca²⁺]_i oscillations that persist for 20 min over a long-term of 24 h or even several days within the plant cytosol and chloroplast. This study investigated the increase in [Ca²⁺]_i under a gradient of low pH stress ranging from pH 3.0 to 6.0. Notably, the peak of [Ca²⁺]_i elevation was lower at pH 4.0 than at pH 3.0 during the initial 8 h, while other pH levels did not significantly increase [Ca²⁺]_i compared to low acidic stress conditions. Lanthanum chloride (LaCl₃) can effectively suppress the influx of [Ca²⁺]_i from the apoplastic to the cytoplasm in plants under acid stress, with no discernible difference in intracellular calcium levels observed in Arabidopsis. Following 8 h of acid treatment in the darkness, the intracellular baseline Ca²⁺ levels in Arabidopsis were significantly elevated when exposed to low pH stress. A moderately low pH, specifically 4.0, may function as a spatial-temporal input into the circadian clock system. These findings suggest that acid stimulation can exert a continuous influence on intracellular calcium levels, as well as plant growth and development. Full article

Background: Inflammatory bowel disease (IBD) is a chronic condition characterized by recurrent episodes and an unclear etiology. Given the limitations of current therapeutic options, which include suboptimal efficacy and significant side effects, there is a pressing need to explore novel treatments. Probiotics derived from diverse species have been identified as a promising approach for managing IBD, owing to their anti-inflammatory properties and their ability to regulate gut flora, among other beneficial effects. Methods: In this study, three strains of lactic acid bacteria (LAB) were isolated from the feces of the scavenger spotted hyena (Crocuta crocuta), a scavenging mammal. Based on their capability to survive within and adhere to the gastrointestinal tract, along with their profile of antibiotic resistance, a high-quality strain of Lactobacillus acidophilus (LA) was selected and demonstrated to be safe for mice. Subsequently, the therapeutic efficacy of LA was evaluated using a dextran sulfate sodium (DSS)-induced model of ulcerative colitis in mice. Results: The results indicated that LA restored the disease activity index and improved histopathological lesions in the model group. It also reduced inflammation and oxidative stress and significantly restored the expression of mucins and intestinal tight junction (TJ) proteins (ZO-1, Occludin). Furthermore, LA corrected the DSS-induced disruption of the intestinal flora, leading to a significant decrease in the prevalence of potentially harmful bacterial genera, such as Bacteroides, and an increase in beneficial bacterial genera, including Lactobacillus. In conclusion, Lactobacillus acidophilus LA1, isolated from spotted hyena feces, has potential as a functional supplement for alleviating symptoms of IBD and regulating intestinal flora. Full article