Search Results (2,443)

Chronic venous disease (CVD) is a prevalent condition in adults, significantly affecting the global elderly population, with a higher incidence in women than in men. The modulation of gene expression through microRNA (miRNA) partly regulated the development of cardiovascular disease (CVD). Previous research identified a functional analysis of seven genes (CDS2, HDAC5, PPP6R2, PRRC2B, TBC1D22A, WNK1, and PABPC3) as targets of miRNAs related to CVD. In this context, miRNAs emerge as essential candidates for CVD diagnosis, representing novel molecular and biological knowledge. This work aims to identify, by network analysis, the miRNAs involved in CVD as potential biomarkers, either by interacting with small molecules such as toxins and pollutants or by searching for new drugs. Our study shows an updated landscape of the signaling pathways involving miRNAs in CVD pathology. This latest research includes data found through experimental tests and uses predictions to propose both miRNAs and genes as potential biomarkers to develop diagnostic and therapeutic methods for the early detection of CVD in the clinical setting. In addition, our pharmacological network analysis has, for the first time, shown how to use these potential biomarkers to find small molecules that may regulate them. Between the small molecules in this research, toxins, pollutants, and drugs showed outstanding interactions with these miRNAs. One of them, hesperidin, a widely prescribed drug for treating CVD and modulating the gene expression associated with CVD, was used as a reference for searching for new molecules that may interact with miRNAs involved in CVD. Among the drugs that exhibit the same miRNA expression profile as hesperidin, potential candidates include desoximetasone, curcumin, flurandrenolide, trifluridine, fludrocortisone, diflorasone, gemcitabine, floxuridine, and reversine. Further investigation of these drugs is essential to improve the treatment of cardiovascular disease. Additionally, supporting the clinical use of miRNAs as biomarkers for diagnosing and predicting CVD is crucial. Full article

Protein-based emulsion gels are an ideal delivery system due to their unique structure, remarkable encapsulation efficiency, and tunable digestive behavior. Freshwater mussel (Solenaia oleivora) protein isolate (SoPI), an emerging sustainable protein with high nutritional value, possesses unique value in the development of functional foods. Herein, composite emulsion gels were fabricated with SoPI and κ-carrageenan (κ-CG) for the delivery of curcumin. SoPI/κ-CG stabilized emulsions possessed a high encapsulation efficiency of curcumin with a value of around 95%. The addition of κ-CG above 0.50% facilitated the emulsion gel formation and significantly improved the gel strength with 1326 g. Furthermore, the storage and digestive stability of curcumin were significantly improved as the κ-CG concentration increased. At 1.50% κ-CG, around 80% and 90% curcumin remained after 21-day storage at 45 °C and the 6 h in vitro gastrointestinal digestion, respectively. The addition of 0.50% κ-CG obtained the highest bioaccessibility of curcumin (~60%). This study illustrated the potential of SoPI emulsion gels as a carrier for stabilizing and delivering hydrophobic polyphenols. Full article

T-cell acute lymphoblastic leukemia (T-ALL) is a challenging childhood cancer to treat, with limited therapeutic options and high relapse rates. This study explores deamidated triosephosphate isomerase (dTPI) as a novel therapeutic target. We hypothesized that selectively inhibiting dTPI could reduce T-ALL cell viability without affecting normal T lymphocytes. Computational modeling and recombinant enzyme assays revealed that disulfiram (DS) and curcumin (CU) selectively bind and inhibit dTPI activity without affecting the non-deamidated enzyme. At the cellular level, treatment with DS and CU significantly reduced Jurkat T-ALL cell viability and endogenous TPI enzymatic activity, with no effect on normal T lymphocytes, whereas the combination of sodium dichloroacetate (DCA) with DS or CU showed synergistic effects. Furthermore, we demonstrated that dTPI was present and accumulated only in Jurkat cells, confirming our hypothesis. Finally, flow cytometry confirmed apoptosis in Jurkat cells after treatment with DS and CU or their combination with DCA. These findings strongly suggest that targeting dTPI represents a promising and selective target for T-ALL therapy. Full article

The major constituent of turmeric, curcumin, is a bioactive phenolic compound that has been studied for its potential health benefits and therapeutic properties. Within this article, the anti-inflammatory, antioxidant and antithrombotic properties and mechanisms of action of curcumin are thoroughly reviewed and the main focus is shifted to its associated health-promoting effects against inflammation-related chronic disorders. An overview of the cardio-protective, anti-tumor, anti-diabetic, anti-obesity, anti-microbial and neuro–protective health-promoting properties of curcumin are thoroughly reviewed, while relative outcomes obtained from clinical trials are also presented. Emphasis is given to the wound-healing properties of curcumin, as presented by several studies and clinical trials, which further promote the application of curcumin as a bioactive ingredient in several functional products, including functional foods, nutraceuticals, cosmetics and drugs. Limitations and future perspectives of such uses of curcumin as a bio-functional ingredient are also discussed. Full article

Background/Objectives: A key role of extracellular vesicles (EVs) is mediating both cell–cell and cell–stroma communication in pathological/physiological conditions. EVs from resistant tumor cells can transport different molecules like P-glycoprotein (P-gp), acting as a shuttle between donor and recipient cells, resulting in a phenotypic change. The aim of our work was to isolate, characterize, and inhibit the release of EVs in two multidrug resistance (MDR) cancer models: MCF-7R (breast cancer cell line) and HL-60R (acute myeloid leukemia cell line). Methods: The existence of P-gp in EVs from MDR cells was confirmed by Western blotting assays. The characterization of EVs was carried out by evaluating the size using NTA and the presence of specific markers such as CD63, Hsp70 and Syntenin. The ability of HL-60R and MCF-7R to perform horizontal transfer of P-gp via EVs to sensitive cells was assessed using three different methods. The acquisition of resistance and its inhibition in recipient cells was confirmed by MTS 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Results: Our data showed that cell lines (MDR) release P-gp-loaded EVs, unlike sensitive cells. The acquisition of resistance determined by the incorporation of P-gp into the membrane of sensitive cells was confirmed by the reduced cytotoxic activity of doxorubicin. Natural compounds such as curcumin, lupeol, and heptacosane can block vesicular transfer and restore the sensitivity of HL-60 and MCF-7 cells. Conclusions: Our study demonstrates that natural inhibitors able to reverse this mechanism may represent a new therapeutic strategy to limit the propagation of the resistant phenotype. Full article

Psoriasis is a chronic inflammatory skin disorder characterized by immune dysregulation and aberrant keratinocyte proliferation. Despite tremendous advances in understanding its etiology, effective therapies that target its fundamental mechanisms remain necessary. Recent research highlights the role of reactive oxygen species dysregulation and mitochondrial dysfunction in psoriasis pathogenesis. Mitochondrial reactive oxygen species mediate cellular signaling pathways involved in psoriasis, such as proliferation, apoptosis, and inflammation, leading to oxidative stress, exacerbating inflammation and tissue damage if dysregulated. This review explores oxidative stress biomarkers and parameters in psoriasis, including myeloperoxidase, paraoxonase, sirtuins, superoxide dismutase, catalase, malondialdehyde, oxidative stress index, total oxidant status, and total antioxidant status. These markers provide insights into disease mechanisms and potential diagnostic and therapeutic targets. Modulating mitochondrial reactive oxygen species levels and enhancing antioxidant defenses can alleviate inflammation and oxidative damage, improving patient outcomes. Natural antioxidants like quercetin, curcumin, gingerol, resveratrol, and other antioxidants show promise as complementary treatments targeting oxidative stress and mitochondrial dysfunction. This review aims to guide the development of personalized therapeutic methods and diagnostic techniques, emphasizing the importance of comprehensive clinical studies to validate the efficacy and safety of these interventions, paving the way for more effective and holistic psoriasis care. Full article

Metabolic-Associated Fatty Liver Disease (MAFLD) is a clinical–pathological scenario that occurs due to the accumulation of triglycerides in hepatocytes which is considered a significant cause of liver conditions and contributes to an increased risk of death worldwide. Even though the possible causes of MAFLD can involve the interaction of genetics, hormones, and nutrition, lifestyle (diet and sedentary lifestyle) is the most influential factor in developing this condition. Polyphenols comprise many natural chemical compounds that can be helpful in managing metabolic diseases. Therefore, the aim of this review was to investigate the impact of oxidative stress, inflammation, mitochondrial dysfunction, and the role of polyphenols in managing MAFLD. Some polyphenols can reverse part of the liver damage related to inflammation, oxidative stress, or mitochondrial dysfunction, and among them are anthocyanin, baicalin, catechin, curcumin, chlorogenic acid, didymin, epigallocatechin-3-gallate, luteolin, mangiferin, puerarin, punicalagin, resveratrol, and silymarin. These compounds have actions in reducing plasma liver enzymes, body mass index, waist circumference, adipose visceral indices, lipids, glycated hemoglobin, insulin resistance, and the HOMA index. They also reduce nuclear factor-KB (NF-KB), interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), blood pressure, liver fat content, steatosis index, and fibrosis. On the other hand, they can improve HDL-c, adiponectin levels, and fibrogenesis markers. These results show that polyphenols are promising in the prevention and treatment of MAFLD. Full article

Mycotoxins are a major threat to animal and human health, as well as to the global feed supply chain. Among them, aflatoxins, fumonisins, zearalenone, T-2 toxins, deoxynivalenol, and Alternaria toxins are the most common mycotoxins found in animal feed, with genotoxic, cytotoxic, carcinogenic, and mutagenic effects that concern the animal industry. The chronic negative effects of mycotoxins on animal health and production and the negative economic impact on the livestock industry make it crucial to develop and implement solutions to mitigate mycotoxins. In this review, we summarize the current knowledge of the mycotoxicosis effect in livestock animals as a result of their contaminated diet. In addition, we discuss the potential of five promising phytogenics (curcumin, silymarin, grape pomace, olive pomace, and orange peel extracts) with demonstrated positive effects on animal performance and health, to present them as potential anti-mycotoxin solutions. We describe the composition and the main promising characteristics of these bioactive compounds that can exert beneficial effects on animal health and performance, and how these phytogenic feed additives can help to alleviate mycotoxins’ deleterious effects. Full article

Curcumin, a polyphenolic compound derived from the widely used spice Curcuma longa, has shown anti-atherosclerotic effects in animal models and cultured vascular cells. Inflammation is a major contributor to atherosclerosis development and progression. We previously reported that the induction of the proinflammatory molecule TRAF3IP2 (TRAF3 Interacting Protein 2) or inhibition of the matrix metallopeptidase (MMP) regulator RECK (REversion Inducing Cysteine Rich Protein with Kazal Motifs) contributes to pro-oxidant, proinflammatory, pro-mitogenic and pro-migratory effects in response to external stimuli in vascular smooth muscle cells. Here we hypothesized that EF24, a curcumin analog with a better bioavailability and bioactivity profile, reverses interleukin (IL)-18-induced TRAF3IP2 induction, RECK suppression and the proinflammatory phenotype of primary human aortic smooth muscle cells (ASMC). The exposure of ASMC to functionally active recombinant human IL-18 (10 ng/mL) upregulated TRAF3IP2 mRNA and protein expression, but markedly suppressed RECK in a time-dependent manner. Further investigations revealed that IL-18 inhibited both miR-30a and miR-342 in a p38 MAPK- and JNK-dependent manner, and while miR-30a mimic blunted IL-18-induced TRAF3IP2 expression, miR-342 mimic restored RECK expression. Further, IL-18 induced ASMC migration, proliferation and proinflammatory phenotype switching, and these effects were attenuated by TRAF3IP2 silencing, and the forced expression of RECK or EF24. Together, these results suggest that the curcumin analog EF24, either alone or as an adjunctive therapy, has the potential to delay the development and progression of atherosclerosis and other vascular inflammatory and proliferative diseases by differentially regulating TRAF3IP2 and RECK expression in ASMC. Full article

The risk of developing cardiovascular disease (CVD) escalates in women during menopause, which is associated with increased vascular endothelial dysfunction, arterial stiffness, and vascular remodeling. Meanwhile, curcumin has been demonstrated to enhance vascular function and structure in various studies. Therefore, this study systematically reviewed the recent literature regarding the potential role of curcumin in modulating vascular function and structure during menopause. The Ovid MEDLINE, PubMed, Scopus, and Web of Science electronic databases were searched to identify relevant articles. Clinical and preclinical studies involving menopausal women and postmenopausal animal models with outcomes related to vascular function or structure were included. After thorough screening, seven articles were selected for data extraction, comprising three animal studies and four clinical trials. The findings from this review suggested that curcumin has beneficial effects on vascular function and structure during menopause by addressing endothelial function, arterial compliance, hemodynamic parameters, and the formation of atherosclerotic lesions. Therefore, curcumin has the potential to be utilized as a supplement to enhance vascular health in menopausal women. However, larger-scale clinical trials employing gold-standard techniques to evaluate vascular health in menopausal women are necessary to validate the preliminary results obtained from small-scale randomized clinical trials involving curcumin supplementation (INPLASY, INPLASY202430043). Full article

Objective: This study aimed to investigate the feasibility of using the digital image processing technique, developed to semi-quantitatively study dermal penetration, to study corneal penetration in an ex vivo porcine eye model. Here, we investigated various formulation strategies intended to enhance dermal and corneal bioavailability of the model hydrophobic drug, curcumin. Methods: Several formulation principles were explored, including oily solutions, oily suspensions, aqueous nanosuspension, micelles, liposomes and cyclodextrins. The dermal penetration efficacy was tested using an ex vivo porcine ear model previously developed at Philipps-Universität Marburg with subsequent digital image processing. This image analysis method was further applied to study corneal penetration using an ex vivo porcine whole-eye model. Results: For dermal penetration, oily solutions, oily suspensions and nanosuspensions exhibited the least penetration, whereas liposomes and cyclodextrins showed enhanced penetration. Corneal curcumin penetration correlated with dermal penetration, with curcumin loaded into cyclodextrins penetrating the deepest. Conclusions: Overall, our study suggests that the image analysis method previously developed for ex vivo skin penetration can easily be repurposed to study corneal penetration of hydrophobic drugs. Full article

In the eukaryotic cells, the ubiquitin–proteasome system (UPS) plays a crucial role in the intracellular protein turnover. It is involved in several cellular functions such as the control of the regular cell cycle progression, the immune surveillance, and the homeostasis. Within the 20S proteasome barrel-like structure, the catalytic subunits, β1, β2 and β5, are responsible for different proteolytic activities: caspase-like (C-L), trypsin-like (T-L) and chymotrypsin-like (ChT-L), respectively. The β5 subunit is particularly targeted for its role in antitumor activity: the synthesis of β5 subunit inhibitors could be a promising strategy for the treatment of solid and hematologic tumors. In the present work, we performed two combination studies of AM12, a recently developed synthetic proteasome inhibitor, with curcumin and quercetin, two nutraceuticals endowed of many pharmacological properties. We measured the combination index (CI), applying the Chou and Talalay method, comparing the two studies, from 50% to 90% of proteasome inhibition. In the case of the combination AM12 + curcumin, an increasing synergism was observed from 50% to 90% of proteasome inhibition, while in the case of the combination AM12 + quercetin an additive effect was observed only from 50% to 70% of β5 subunit inhibition. These results suggest that combining AM12 with curcumin is a more promising strategy than combining it with quercetin for potential therapeutic applications, especially in treating tumors. Full article

Curcumin (Cur), the primary curcuminoid found in Curcuma longa L., has garnered significant attention for its potential anti-inflammatory and antibacterial properties. However, its hydrophobic nature significantly limits its bioavailability. Additionally, adipose-derived stem cells (ADSCs) possess immunomodulatory properties, making them useful for treating inflammatory and autoimmune conditions. This study aims to verify the efficacy of poly(ε-caprolactone) nanocapsules (NCs) in improving Cur’s bioavailability, antibacterial, and immunomodulatory activities. The Cur-loaded nanocapsules (Cur-NCs) were characterized for their physicochemical properties (particle size, polydispersity index, Zeta potential, and encapsulation efficiency) and stability over time. A digestion test simulated the behavior of Cur-NCs in the gastrointestinal tract. Micellar phase analyses evaluated the Cur-NCs’ bioaccessibility. The antibacterial activity of free Cur, NCs, and Cur-NCs against various Gram-positive and Gram-negative strains was determined using the microdilution method. ADSC viability, treated with Cur-NCs and Cur-NCs in the presence or absence of lipopolysaccharide, was analyzed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay. Additionally, ADSC survival was assessed through the Muse apoptotic assay. The expression of both pro-inflammatory (interleukin-1β and tumor necrosis factor-α) and anti-inflammatory (IL-10 and transforming growth factor-β) cytokines on ADSCs was evaluated by real-time polymerase chain reaction. The results demonstrated high stability post-gastric digestion of Cur-NCs and elevated bioaccessibility of Cur post-intestinal digestion. Moreover, Cur-NCs exhibited antibacterial activity against Escherichia coli without affecting Lactobacillus growth. No significant changes in the viability and survival of ADSCs were observed under the experimental conditions. Finally, Cur-NCs modulated the expression of both pro- and anti-inflammatory cytokines in ADSCs exposed to inflammatory stimuli. Collectively, these findings highlight the potential of Cur-NCs to enhance Cur’s bioavailability and therapeutic efficacy, particularly in cell-based treatments for inflammatory diseases and intestinal dysbiosis. Full article

Bone defects caused by surgical interventions and the challenges of tumor recurrence and metastasis due to residual cancer cells significantly complicate the treatment of osteosarcoma (OS). To address these complex clinical challenges, we propose an innovative therapeutic strategy that centers on an ultrasound-activated multifunctional bioactive calcium phosphate (BioCaP) composite. A modified curcumin (mcur)-mediated wet biomimetic mineralization process was used to develop an anticancer-drug-integrated multifunctional BioCaP (mcur@BioCaP), exploring its potential biological effects for OS treatment activated by ultrasound (US). The mcur@BioCaP demonstrates a drug dose-dependent, tailorable alteration in its micro/nanostructure. The US stimulus significantly enhanced this composite to generate reactive oxygen species (ROS) in cancer cells. The results show that the OS cell viability of the mcur@BioCaP with US is 62.2% ± 6.3%, the migration distance is 63.9% ± 6.6%, and the invaded OS cell number is only 57.0 ± 3.7 OS cells per version, which were all significantly lower than US or mcur@BioCaP alone, suggesting that the anticancer, anti-migratory and anti-invasive effects of mcur@BioCaP on OS 143B cells were amplified by ultrasonic stimulation. This amplification can be attributed to the US-activated ROS production from the drug molecules, which regulates the wet biomimetic mineralization of the multifunctional composite. Furthermore, mcur@BioCaP with US increased calcium nodule formation by 1.8-fold, which was significantly higher than mcur@BioCaP or US group, indicating its potential in promoting bone regeneration. The anticancer and osteogenic potentials of mcur@BioCaP were found to be consistent with the mcur concentration in the multifunctional composite. Our research provides a novel therapeutic approach that leverages a multifunctional biomimetic mineral and ultrasonic activation, highlighting its potential applications in OS therapy. Full article

In this study, we developed sodium alginate-chitosan hydrogels using a microwave-assisted synthesis method, aligning with green chemistry principles for enhanced sustainability. This eco-friendly approach minimizes chemical use and waste while boosting efficiency. A curcumin:2-hydroxypropyl-β-cyclodextrin complex was incorporated into the hydrogels, significantly increasing the solubility and bioavailability of curcumin. Fourier Transform Infrared Spectroscopy (FTIR) analysis confirmed the structure and successful incorporation of curcumin, in both its pure and complexed forms, into the polymer matrix. Differential scanning calorimetry revealed distinct thermal transitions influenced by the hydrogel composition and physical cross-linking. Hydrogels with higher alginate content had higher swelling ratios (338%), while those with more chitosan showed the lowest swelling ratios (254%). Scanning Electron Microscopy (SEM) micrographs showed a porous structure as well as successful incorporation of curcumin or its complex. Curcumin release studies indicated varying releasing rates between its pure and complexed forms. The chitosan-dominant hydrogel exhibited the slowest release rate of pure curcumin, while the alginate-dominant hydrogel exhibited the fastest. Conversely, for curcumin from the inclusion complex, a higher chitosan proportion led to the fastest release rate, while a higher alginate proportion resulted in the slowest. This study demonstrates that the form of curcumin incorporation and gel matrix composition critically influence the release profile. Our findings offer valuable insights for designing effective curcumin delivery systems, representing a significant advancement in biodegradable and sustainable drug delivery technologies. Full article