Search Results (20,161)

Multidrug resistance (MDR) remains a major obstacle in the treatment of ovarian cancer. MDR is often mediated by the overexpression of ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). In this study, we evaluated the ability of elacridar, a dual P-gp and BCRP inhibitor, to overcome MDR in W1, an ovarian cancer cell line sensitive to Paclitaxel (PAC) and its PAC-resistant variants. Cells were cultured under both two-dimensional (2D) and three-dimensional (3D) conditions to account for differences in tumor-like microenvironments. The MDR1 gene and P-gp protein expression were determined for the analyzed model; P-gp activity was measured by flow-cytometry and fluorescent observation, with and without elacridar. The MTT tests were carried out to evaluate how elacridar, combined with chemotherapeutics, affects cell viability. Our results demonstrate that elacridar effectively inhibited transporter activity and increased cellular sensitivity to PAC and DOX. The inhibitory effect was observed in both 2D and 3D cultures, although the re-sensitization effect in 3D conditions was less pronounced, reflecting the complexity of tumor-specific resistance mechanisms. These findings highlight elacridar as a promising compound for reversing MDR in ovarian cancer and emphasize the importance of 3D models in preclinical drug evaluation. Further studies in advanced in vitro and in vivo models are required to assess the potential of elacridar better. Full article

Shots are becoming increasingly popular due to their convenience and concentrated nutrient content. In this study, innovative shots were developed as herbal-enriched formulations designed to improve bioaccessibility, bioavailability, and health-promoting properties. To achieve this, pear–flowering quince juice was enriched with a mixture of herbal infusions and evaluated for its physicochemical characteristics, including bioactive compounds, as well as its functional and sensory properties. Additionally, the products were subjected to a three-stage in vitro digestion model (oral–gastric–small intestine) to assess bioaccessibility and bioavailability. The results revealed that the shot containing mint and nettle had the highest polyphenolic content (579 mg/100 mL), while the shot enriched with white mulberry and common yarrow had the highest mineral content (28 mg/100 mL). The developed formulations also exhibited strong inhibitory effects on pancreatic lipase and lipoxygenase. It was demonstrated that the addition of selected herbs, particularly those rich in rosmarinic acid, can enhance both bioaccessibility and bioavailability, and that menthol may further potentiate these effects. In conclusion, the study showed that incorporating different types of herbs into pear–flowering quince juice enables the development of novel products with tailored health-promoting and sensory properties, primarily through the synergistic action of the individual ingredients. Full article

Recent research has focused on yogurts supplemented with plant-derived and apiculture ingredients to enhance functional properties. This study evaluates the symbiotic potential of provitamin A carotenoids, dietary fiber, and oligosaccharides from carrots, mangoes, and honeydew honey in probiotic-enriched bioyogurt. Formulations were assessed during fermentation (45 °C ± 1 °C for 5 h) and refrigerated storage (4 °C ± 1 °C for 21 days). Probiotic and starter culture viability was determined using pour-plate counts on MRS agar. Physicochemical parameters including pH, titratable acidity, total soluble solids, water-holding capacity, and antioxidant metrics (total phenolics and carotenoids) were analyzed. After 21 days of storage, the probiotic culture (VEGE 092) reached 10.26 log CFU/mL and the starter culture (YOFLEX) achieved 8.66 log CFU/mL, maintaining therapeutic thresholds. Total carotenoid content increased significantly (p < 0.05) from 2.15 to 3.96 µg β-carotene/g, indicating synergistic interactions between lactic acid bacteria and plant-derived bioactive compounds. These findings demonstrate that combining plant-derived carotenoids, prebiotic fibers, and honeydew oligosaccharides effectively maintains probiotic viability and enhances antioxidant stability throughout fermentation and refrigerated storage, supporting the development of functional dairy products with improved nutritional profiles. Full article

TANGO2 deficiency disorder is a rare autosomal recessive disease (~100 cases reported worldwide). Despite being caused by loss-of-function variants in the TANGO2 gene, patients exhibit marked phenotypic variability, including intrafamilial differences among individuals carrying identical variants. To uncover potential modifier mechanisms influencing disease severity, we developed an integrative Systems biology framework, combining exome sequencing, transcriptomics, variant effect prediction, and Human Phenotype Ontology mapping. This approach was applied to two siblings carrying identical compound heterozygous TANGO2 variants but opposite clinical outcomes: one severely affected and one asymptomatic. Personalized protein–protein interaction networks and combined univariate and multivariate analyses were employed to maximize specificity in this single-family comparison. In the affected sibling, a cumulative burden of common APOB variants, together with altered VLDLR, NTN1, and LDHA expression, implicated disrupted lipid metabolism and neurodevelopmental pathways. The asymptomatic sibling harbored a potentially protective 3′-UTR variant in EP300 and no APOB variant burden, supporting enhanced post-transcriptional regulation within developmental biology networks. These findings highlight lipid metabolism as a key pathway in TANGO2 deficiency pathophysiology and suggest autophagy and mitophagy as additional modifier mechanisms influencing phenotypic variability. Our integrative multi-omics framework provides a valuable strategy for elucidating genotype-phenotype relationships in rare diseases and supports personalized therapeutic approaches. Full article

Oxidative stress, inflammation, and environmental factors contribute significantly to the development of ocular disorders, including dry eye disease, conjunctivitis, and age-related degenerative changes. In recent years, growing attention has been directed toward natural compounds and plant-derived extracts with potential protective and therapeutic effects on eye health. This work provides an overview of selected bioactive substances, such as carotenoids (β-carotene), flavonoids, vitamins C and E, and phytochemicals derived from plants. These agents exhibit antioxidative, anti-inflammatory, antimicrobial, and regenerative properties that may support ocular surface integrity, reduce oxidative damage, and improve visual performance. The integration of such natural remedies into ocular health strategies may offer complementary benefits to conventional therapies. Full article

Fleas have major veterinary and public health relevance by causing dermatopathies and transmitting zoonotic agents. The limitations and environmental impact of synthetic insecticides have driven the search for safer and more sustainable tick control alternatives, such as essential oils (EOs) and their bioactive compounds. We conducted searches in the PubMed, Scopus and Google Scholar databases (May–August 2025), using predefined inclusion and exclusion criteria, resulting in 25 studies. The species investigated most was Ctenocephalides felis, followed by Xenopsylla cheopis. The most common botanical families were Lamiaceae, Cupressaceae, Rutaceae, and Lauraceae, comprising 48 plant species. For C. felis, the EOs of Cinnamomum spp., Ocimum gratissimum, Syzygium aromaticum and Piper aduncum showed the most pronounced insecticidal effects, as did their bioactive compounds cinnamaldehyde, eugenol, and dillapiole, respectively. For X. cheopis, the EOs of Cinnamomum verum, Calocedrus decurrens, and Salvia rosmarinus were the most effective. Essential oils from different plant species also exhibited repellent activity against C. felis, Pulex irritans and Diamanus montanus. In summary, essential oils and their bioactive compounds have promising potential for the control of fleas of medical and veterinary importance, representing sustainable alternatives with reduced environmental impacts. Full article

Rheumatoid arthritis (RA) and osteoarthritis (OA) are significant global health challenges, fueling the need for innovative therapeutic strategies. Natural polyphenolic compounds, such as green tea catechins, exhibit promising anti-inflammatory, antioxidant, and immunomodulatory properties, making them potential adjuncts to rheumatic disease therapy. This review examines the effects of catechins, particularly epigallocatechin-3-gallate (EGCG), on key pathophysiological processes associated with RA and OA, such as pro-inflammatory cytokine production, oxidative stress, cartilage degradation, angiogenesis, and immune cell activation and proliferation. This study contains experimental data contained in full-text articles published in open-access indexed journals published only in English. The most important conclusions drawn from the in vitro and in vivo studies available so far, as well as studies on patients, show that green tea catechins modulate pro-inflammatory pathways, reduce the level of pro-inflammatory cytokines and improve the condition of the intercellular matrix in joint tissues, limiting the destruction of joint tissues in animals and patients and reducing pain. Although these studies suggest potential benefits, such as reduced inflammation and improved clinical parameters, the number and scale of studies are insufficient to confirm the clinical efficacy in a broad patient population. Therefore, claims of adjunctive therapy to conventional therapies should be interpreted with caution, and further well-designed and more powerful clinical trials are needed to verify the translation of the promising molecular mechanisms of green tea catechins into clinical practice. Full article

Background: To meet the urgent need for novel antibacterial agents that are active also against worrying superbugs, natural pentacyclic triterpenoids, including totally inactive betulin (BET) and betulinic acid (BA), as well as ursolic acid (UA), active on Gram-positive bacteria, have been chemically modified, achieving compounds 1–7. Methods: Triterpenoid derivatives 1–7 and all synthetic intermediates were characterized by chemometric-assisted FTIR and NMR spectroscopy, as well as by other analytical techniques, which confirmed their structure and high purity. Minimum inhibitory concentration values (MICs) of 1–7, BET, BA and UA were determined by the broth dilution method, using a selection of Gram-positive and Gram-negative clinically isolated superbugs. Results: Performed experiments evidenced that compounds 4–7 had potent antibacterial effects against Gram-positive methicillin-resistant Staphylococcus aureus and S. epidermidis (MRSA and MRSE), as well as against vancomycin-resistant Enterococcus faecalis and E. faecium (VRE). The antibacterial effects of 4–7 were due to the insertion of a triphenyl phosphonium (TPP) group and were higher than those reported so far for other BET, BA and UA derivatives, especially considering the complex pattern of resistance of the isolates used here and their clinical source. Conclusions: For the first time, by inserting TPP, a real activity (MICs 2–16 µg/mL) was conferred to inactive BET and BA (MICs > 1024 and 256 µg/mL). Moreover, the antibacterial effects of UA were improved 16- and 32-fold against MRSE and MRSA (MICs = 2 vs. 32 and 64 μg/mL). Future Perspectives: Based on these very promising microbiologic results, new experiments are currently underway with the best-performing compounds 5 and 7 (MICs = 2 μg/mL) on an enlarged number of Gram-positive isolates, to confirm their MICs. Moreover, investigations about their possible antibiofilm activity, time-killing curves and cytotoxicity on eukaryotic cells will be carried out to define their pharmacological behavior and clinical potential. Full article

Prostate cancer (PCa) is the second most prevalent cancer among men and a major cause of cancer-related mortality worldwide. Despite an initial favorable response to hormone-based therapies, many patients ultimately develop an advanced and lethal form of the disease, referred to as castration-resistant PCa (CRPC). CRPC is associated with poor prognosis and a lack of effective curative treatments. As a result, new alternatives or improved therapeutic strategies to combat this life-threatening condition are urgently needed. Chalcones, also referred to as 1,3-diphenyl-2-propen-1-ones, have attracted significant attention because of their potent antitumor properties. Owing to their distinctive chemical structure and diverse biological activities, these compounds are promising candidates for treating various cancers, including PCa. Both naturally occurring and synthetically derived chalcones have demonstrated anticancer potential by modulating key cellular processes, including apoptosis, cell cycle regulation, cell migration, invasion, metastasis and angiogenesis, as well as major signaling pathways, such as PI3K/Akt/mTOR, androgen signaling, and NF-κB. This review aims to outline the recent advances in the therapeutic potential of chalcone derivatives in prostate cancer, with a focus on their molecular targets, mechanisms of action, and translational relevance. Full article

Silicone is widely used in medical devices due to its mechanical properties and biocompatibility; however, microbial contamination of silicone surfaces, which can lead to nosocomial infections, remains a significant concern. This can be countered by surface modification using techniques commonly involving oxidative plasma activation or ozone treatments, followed by treatment with silanization agents. Here, we report an alternative surface modification procedure involving treatment with non-toxic organic hydroxyl amines or diamine dissolved in eco-friendly solvents, thus avoiding using reactive and potentially harmful compounds and not requiring specialized equipment. Our findings demonstrate that ethanolamine in isopropanol effectively activates silicone without compromising its tensile strength, making it ideal for further modification. The activated surfaces showed stable amino group areal concentrations over a 10-day period, confirmed by fluorescence imaging and ninhydrin assays. Subsequent treatments with glutaraldehyde and chitosan enhanced the antibacterial properties of the silicone. Chitosan-coated silicone significantly reduced Gram-positive and Gram-negative bacteria colony-forming units (CFUs), with Enterococcus faecalis CFUs decreasing from 7.1 to 3.7 Log₁₀ CFU/mL. This study introduces a sustainable activation technique for silicone surfaces, resulting in medical devices with improved resistance to microbial colonization while maintaining their mechanical integrity. Full article

Background/Objectives: Giardia lamblia is an intestinal protozoan responsible for giardiasis, a globally prevalent parasitic disease. Current therapeutic options, including nitroimidazoles and benzimidazoles, have increasing treatment failures due to resistance, adverse reactions, and patient non-compliance. Drug repositioning offers a cost-effective strategy for identifying new antigiardial agents. This study aimed to evaluate the in vitro antiparasitic effects and possible mechanisms of action of the tricyclic antidepressant imipramine against G. lamblia trophozoites. Methods: Trophozoites were exposed to increasing concentrations of imipramine (25–125 µM). Growth inhibition and adhesion capacity were quantified using cell counts. Apoptosis- or necrosis-like death was evaluated through Annexin V/PI staining. The expression and distribution of α-tubulin and lipid rafts were analyzed by immunofluorescence microscopy. Finally, the effect of the drug on encystment efficiency was assessed in vitro. Results: Imipramine inhibited G. lamblia trophozoite growth in a concentration-dependent manner, with an IC₅₀ of 42.31 µM at 48 h. The drug significantly reduced adhesion capacity (>90% at 125 µM) and induced apoptosis-like cell death, as evidenced by Annexin V positivity. Immunofluorescence revealed disruption of α-tubulin distribution and lipid raft organization, accompanied by morphological rounding. Moreover, encystment efficiency decreased in a concentration-dependent mode, suggesting interference in the differentiation process. Conclusions: This investigation describes, for the first time, the antigiardial potential of imipramine, which alters cytoskeletal organization, membrane microdomains, and differentiation pathways, ultimately leading to apoptosis-like cell death. These findings position this compound as a promising lead structure and support further exploration of tricyclic antidepressants as scaffolds for the development and optimization of new antiparasitic agents, as well as future studies on their molecular targets and in vivo efficacy. Full article

Natural products are a valuable source of bioactive compounds with established roles in oncology. Their structural diversity and ability to target multiple cancer-related pathways make them promising candidates for anticancer drug development. Increasing preclinical and clinical data highlight their potential not only to exert direct antitumor effects but also to enhance patient tolerance to conventional therapies by reducing side effects and improving treatment adherence. The Mediterranean region, known for its biodiversity and traditional dietary habits, provides a rich array of natural compounds with documented health benefits. Key Mediterranean natural plant products (MNPPs), including bioactives from olive oil, onion, citrus fruits, chili pepper and grapes, exhibit antioxidant, anti-inflammatory, and anti-proliferative properties. This review focuses on the molecular mechanisms of selected MNPPs, such as polyphenols, flavonoids, alkaloids, terpenes, organosulfur and furanocoumarin compounds, which modulate oxidative stress, inflammation, apoptosis, and tumor progression. Evidence from in vitro and in vivo studies supports their role in cancer prevention and as adjuvants in therapy. While further clinical research is needed, these findings suggest that incorporating MNPPs into therapeutic regimens could offer low-toxicity, multi-targeted support in oncology, improving both outcomes and quality of life in cancer patients. Full article

Background/Objectives: Plant-derived diuretics are attracting increasing interest due to their promising efficacy and improved safety profile compared with synthetic drugs. This study aimed to characterize the phytochemical composition of Astragalus boeticus (A. boeticus) extracts, evaluate their diuretic activity, and assess the oral safety of their main phenolic compound. Methods: Aqueous (AQE) and hydroethanolic (EtOHE) extracts were analyzed using LC–MS/MS, while in silico toxicity prediction of trans-resveratrol was performed using ProTox-II and ADMETlab 2.0. Diuretic activity was evaluated in male Wistar rats (n = 24) divided into four groups: control (distilled water, 10 mL/kg), furosemide (10 mg/kg), AQE (300 mg/kg), and EtOHE (300 mg/kg). Urine and plasma samples were collected after 15 days to determine electrolyte concentrations, creatinine level, creatinine clearance, and hepatic enzyme profile. Results: LC–MS/MS profiling identified fourteen phenolic compounds, with trans-resveratrol (270 µg/g in AQE) being the most abundant, followed by cyanidin-3-O-glucoside and gentisic acid. In silico assessments revealed no hepatotoxic, mutagenic, or neurotoxic effects of trans-resveratrol. Both extracts significantly enhanced urinary output, chloride excretion, and creatinine clearance, while maintaining stable renal and hepatic biochemical parameters, indicating potent diuretic activity without toxicity. Conclusions: A. boeticus extracts demonstrate strong diuretic potential associated with a favorable safety profile, likely linked to their phenolic composition dominated by trans-resveratrol. These findings support the use of A. boeticus as a natural and safe diuretic source. Further investigation is recommended to elucidate its pharmacological mechanisms and therapeutic relevance. Full article

Soybean meal has traditionally dominated poultry diets as the protein source. However, its widespread use raises concerns regarding economic costs, environmental impact and social sustainability. As a result, there is growing interest in alternative protein sources, such as canola meal, which may reduce feed costs while sustaining productivity. This review evaluates the potential of canola meal as a sustainable protein source in modern poultry production systems, focusing on nutritional, economic and environmental advantages, as well as the potential implications of canola meal inclusion in reduced-protein diets. Evidence from scientific studies indicates that canola meal’s nutritional profile supports bird growth and production, although higher fiber content and anti-nutritional compounds reduce metabolizable energy, making it more suitable for laying hens than broiler chickens. Processing techniques, enzyme supplementation, fermentation, and modern cultivars have improved both nutritional value and practical utility of canola meal. Performance outcomes differ by species. Broilers exhibit variable growth at high inclusion levels, whereas laying hens are estimated to tolerate up to 20% without affecting laying performance or egg quality; however, data is severely lacking, particularly under the context of modern reduced-protein diets. Economically, canola meal is cost-competitive with soybean meal. From an environmental perspective, substituting imported soybean meal with local canola reduces greenhouse gas emissions, enhances resource efficiency, and supports pollinators. Nevertheless, trade-offs exist, including increased land use, variable digestibility, and potential eutrophication. Incorporating canola meal into reduced-protein diets offers both economic and ecological benefits, though effectiveness depends on the extent of protein reduction and the precision of amino acid formulation. Overall, canola meal offers a sustainable, economically viable, and environmentally responsible protein source for modern poultry production, provided that inclusion levels are adjusted to species-specific requirements and regional conditions. Full article

Treating acute lung injury (ALI) presents significant challenges due to adverse drug reactions. This study systematically explored the protective effects and mechanisms of a flavonoid-rich extract from Bombyx batryticatus (FBB), a traditional Chinese medicine, in combating ALI. Through UPLC-MS/MS analysis, we identified 163 flavonoid components in FBB for the first time, including flavonoids, flavonols, and chalcones. Unlike single-component flavonoid therapies, FBB provides synergistic regulation across multiple targets and pathways. Network pharmacology predictions, supported by experimental validation, revealed that FBB primarily suppresses the expression of inflammatory factors (IL-1β, IL-6, TNF-α) and oxidative stress markers (iNOS, COX-2) by modulating the PI3K/Akt, MAPK, and NF-κB signaling pathways. FBB inhibits pro-inflammatory responses and upregulates chemokine receptors like Ccr1 and Ccr2, along with IL-2Rb, at the transcriptional level. This suggests its potential to promote inflammation resolution and tissue repair through immune microenvironment remodeling, rather than mere immunosuppression. Additionally, FBB demonstrated significant anti-apoptotic effects both in vitro and in vivo, effectively reducing pulmonary edema and vascular permeability. Its complex composition and multi-pathway synergistic mechanisms offer broader regulatory potential and unique therapeutic advantages in treating ALI compared to single flavonoid compounds or conventional hormone drugs like dexamethasone (DEX). This study reveals a novel mechanism by which FBB, a multi-component natural drug, exerts therapeutic effects in ALI, providing a theoretical and experimental foundation for developing flavonoid-based compound preparations from traditional Chinese medicine. Full article