Search Results (192)

Background/Objectives: Skin cancer is a major health concern worldwide and has led to the quest for safer and more effective topical chemopreventive agents. In this study, the in vivo efficacy of a hydrogel formulation containing kaempferol and ferulic acid-loaded nanoparticles was evaluated for the management of DMBA-croton oil-induced skin cancer in Swiss albino mice. Methods: Drug-loaded nanoparticles prepared via nanoprecipitation were incorporated into hyaluronic acid to obtain single-drug (FAPG, KMPG) and dual-drug-loaded (FKMG) hydrogel formulations. Skin tumors were induced via DMBA as an initiator followed by croton oil as a promoter, with tumor onset observed after a similar latency period of approximately 5–6 weeks in all carcinogen-exposed groups. Treatment was initiated after week 6 and continued until week 16. Results: The gel formulation had a skin-compatible pH and the desired rheological and spreadability properties. The dual drug-loaded hydrogel formulation had a more controlled and prolonged release profile. Compared with the negative and vehicle control groups, the FKMG-treated group presented a marked reduction in tumor incidence and tumor burden, along with improved body weight gain. Biochemical analysis revealed the restoration of antioxidant and enzyme activity in treated animals, particularly in animals treated with FKMG. Histopathological examination revealed near-normal skin architecture in FKMG-treated mice, indicating strong protective effects. Additionally, significant downregulation of TNF-α and IL-6 suggested effective suppression of tumor-promoting inflammatory pathways. Conclusions: Overall, the FKMG formulation exhibited superior chemopreventive efficacy compared with the FAPG and KMPG treatments, highlighting its potential as a promising topical therapeutic strategy against chemically induced skin carcinogenesis. Full article

This study evaluated the effects of dietary starch characteristics on intestinal energy metabolism and microbial profiles in Epigallocatechin gallate (EGCG)-supplemented broiler chickens. A total of 300 Arbor Acres male broilers were assigned to five dietary treatments consisting of a corn–soybean basal diet (NC), EGCG supplementation (500 mg/kg) (PC), or diets in which 20% corn was substituted with purified corn (CS), cassava (TS), or pea starch (PS) in the presence of EGCG (500 mg/kg). Growth performance, starch digestion, intestinal energy status, cecal microbiota, and metabolomic profiles were evaluated. The results showed that broilers fed the corn starch-containing diet under EGCG supplementation showed improved average daily gain and feed conversion ratio (p < 0.05). This treatment also increased intestinal ATP and cAMP concentrations while reducing AMP and the AMP/ATP ratio, accompanied by enhanced activities of Na⁺-K⁺-ATPase, citrate synthase, and pyruvate dehydrogenase. Cecal microbiota analysis showed that Lactobacillus abundance was increased in the CS group, whereas Barnesiella was enriched in the PS group. Differential metabolites associated with energy metabolism, including lipoic acid, palmitoylcarnitine, and crotonic acid, were significantly changed among treatments. In conclusion, dietary starch characteristics influenced intestinal energy metabolism-related indicators, microbial profiles, and metabolite patterns in broilers receiving EGCG supplementation. Full article

Cutaneous squamous cell carcinoma (cSCC) is a common malignant skin tumor with invasive potential and risk of recurrence. This study investigated the anti-cSCC effects of luteolin in vitro and in vivo and explored the associated molecular mechanisms. The effects of luteolin on A431 cell viability were assessed by CCK-8 assay, and apoptosis was analyzed by Annexin V-FITC/propidium iodide (PI) double staining. qRT-PCR and Western blot analyses were performed to evaluate apoptosis-related factors and the EGFR/PI3K/AKT signaling pathway. Molecular docking was further conducted to explore the potential interactions of luteolin with EGFR/PI3K/AKT signaling-related proteins and apoptosis-associated proteins. In vivo, a two-stage skin carcinogenesis model induced by 7,12-dimethylbenz[a]anthracene (DMBA) and croton oil was used to evaluate the antitumor activity of luteolin. Luteolin significantly inhibited A431 cell viability and promoted apoptosis in a concentration-dependent manner. Moreover, luteolin increased Bax expression and decreased Bcl-2 expression at both the mRNA and protein levels. Mechanistically, luteolin suppressed the phosphorylation of EGFR, PI3K, and AKT. Molecular docking suggested that luteolin could interact with EGFR, PIK3CA, AKT, Bax, and Bcl-2, providing supportive in silico evidence for its potential modulation of EGFR/PI3K/AKT signaling and apoptosis-related proteins. In vivo, luteolin alleviated body weight loss, achieved a tumor nodule inhibition rate of 45.28%, significantly improved spleen and thymus indices (p < 0.05), and ameliorated histopathological damage in skin tissues. In addition, immunohistochemical analysis showed that luteolin reduced Ki-67 expression. These results indicate that luteolin exerts anti-cSCC effects in vitro and in vivo, possibly through modulation of the EGFR/PI3K/AKT signaling pathway and apoptosis-related proteins. Full article

This review provides a comprehensive overview of the modulatory actions of plant-derived constituents on membrane ion channels in various cell types. Among their diverse bioactivities, ion channel regulation—governing membrane excitability, signal transduction, and cellular homeostasis—has emerged as a critical mechanistic basis for their pharmacological effects. Twenty-four representative phytoconstituents are discussed and classified into five major categories based on their structural features: alkaloids, terpenoids, lignans and acetogenins, polyphenols, and other aromatic and conjugated compounds. Across these categories, the reviewed compounds exhibit distinct and often highly specific effects on the amplitude and gating kinetics of multiple ionic currents, including voltage-gated Na⁺ currents (I_Na), delayed-rectifier K⁺ currents (I_K(DR)), M-type K⁺ currents (I_K(M)), hyperpolarization-activated cation currents (I_h), erg-mediated K⁺ currents (I_K(erg)), inwardly rectifying K⁺ currents, and Ca²⁺-activated K⁺ currents (I_K(Ca)). Alkaloids predominantly suppress voltage-gated K⁺ currents, with notable exceptions such as aconitine, which alters the properties of both I_Na and I_K(DR), thereby contributing to its proarrhythmic toxicity. Terpenoids, including cannabidiol, croton diterpenoids, lutein, thymol, and triptolide, exert multifaceted effects on I_K(M), I_h, inwardly rectifying K⁺ currents, and Ca²⁺-activated K⁺ channels. Lignans and acetogenins, such as gomisin A, honokiol, sesamin, and squamocin, primarily modulate I_Na, I_h, and I_K(Ca), with several compounds demonstrating strong links between ion-channel modulation and anti-neoplastic or neuroprotective actions. Polyphenolic compounds, including curcumin, eugenol, resveratrol, gastrodigenin, gastrodin, and pterostilbene, display diverse ion-channel targeting profiles, influencing multiple Na⁺ and K⁺ channel subtypes. Other aromatic or conjugated compounds, such as isoplumbagin, plumbagin, and verteporfin, regulate I_K(erg) and I_K(Ca), potentially contributing to both therapeutic efficacy and adverse effects. Collectively, the compound-specific modulation of current amplitude and gating kinetics offers valuable mechanistic insight into the pharmacological and toxicological significance of plant-derived natural products, highlighting the functional role of ion channel evaluation in guiding their therapeutic development and ensuring safety assessment. Full article

The paper starts by questioning the highly influential but extremely misleading characterizations of Plato and Hegel by Bertrand Russell and Karl Popper. It is argued that mathematical assumptions concerning the ancient problem of the incommensurability of continuous and discrete quantities underlie the ways in which Russell and Popper portray the metaphysics of Plato and Hegel—Popper explicitly, and Russell implicitly, presupposing a particular response to this problem by broadening the concept of number to include irrational numbers. Recent work on Plato, however, suggests a different strategy for responding to this ancient conundrum, one that involves a mediated “duality” of the continuous and discrete that Hegel would later generalize to a duality of determinate and indeterminate aspects of cognition more generally. This Platonic alternative had originated with the Pythagorean natural philosopher Philolaus of Croton and would later be expressed in modern mathematics in a non-Cartesian way of applying numerical metrics to geometric figures in disciplines such as projective geometry. Such an alternative approach to both quantitative and conceptual incommensurability, I claim, had influenced Plato’s later conception of philosophical method that would be adopted by Hegel via the intermediary of Leibniz, the first modern “idealist”. Understanding the actual mathematics modeling philosophical concepts for Plato and Hegel becomes crucial for understanding the philosophical claims of modern idealism. Full article

A digital colorimetric method (ACETimage), which utilizes aldol condensation, crotonization, and resinification, was developed and validated to quantify acetaldehyde in the head fraction of Pisco distillation. The optimal conditions for the reaction were as follows: the head Pisco samples were placed in headspace vials, 20% w/w NaOH was added, and the mixture was boiled in water for 2 min. The Color Grab app was used to capture and analyze images of the reactions, with a screen brightness intensity of 0.5, within a maximum post-reaction time of 10 min. The Euclidean distance (ED-RGB) was the color parameter most sensitive to changes, showing a linear correlation with the square of acetaldehyde concentration, with R² values ranging from 0.9926 to 0.9976. The limit of detection (LOD) and limit of quantification (LOQ) for the ACETimage method were determined to be 30 and 95.3 mg/L, respectively. A significant correlation was observed between the acetaldehyde content measured using ACETimage and gas chromatography (Spearman’s r = 0.9373). Bland–Altman analysis indicated that the differences between the two methods were within the 95% limits of agreement. ACETimage offers a rapid, cost-effective, and user-friendly solution for monitoring acetaldehyde levels during Pisco distillation, enabling easy implementation in production environments, both artisanal and industrial, with minimal sample preparation and limited personnel training. Full article

Globally, breast cancer is one of the most prevalent tumors in women and remains a major concern due to its high mortality rate. Although treatment options for this disease have evolved over the years, there are still many cases of recurrence and metastasis. In this context, considering the importance of evaluating less aggressive and more efficient therapeutic alternatives to aid in the treatment of breast cancer, the present study critically discusses the cytotoxic effects of diterpenoids isolated from Croton species (Euphorbiaceae). The articles were retrieved from different databases, from the first report published in 2005 to October 2025. A total of 115 diterpenoids were isolated from 15 Croton species and investigated against different breast cancer cell lines (MDA-MB-231, MCF-7, and MDA-MB-468). These compounds mainly belong to the kaurane group (40%), followed by clerodane (14%), tigliane (12%), and abietane (10%). Of this total, only 25 compounds showed promising results (IC₅₀ = < 10 µM). The mechanisms of action of the compounds crokokaugenoid A, kongensin A, kongensin D, ent-16β,17α-dihydroxykaurane, and lauicyclone A have been reported. These compounds likely act by inducing apoptosis, autophagy, cell cycle arrest, inhibition of cell migration and invasion, and DNA fragmentation in breast cancer cell lines. To date, no randomized clinical trials have been conducted using Croton diterpenoids for the treatment of breast cancer. Therefore, further studies on the modulation of the immune response by these natural products are essential to better understand their immunotherapeutic activity in the tumor microenvironment during breast cancer progression. Full article

This study assessed the structural stability and in vitro antioxidant capacity of a cosmetic formulation incorporating sangre de grado extract (Croton lechleri Muell) and vegetable oils from aguaje (Mauritia flexuosa L.f.), aguaymanto (Physalis peruviana L.), super sacha inchi (Plukenetia huayllabambana sp. nov.), and sacha inchi (Plukenetia volubilis L.), sourced from Peruvian biodiversity. Structural characterization was conducted using Attenuated total reflectance Fourier transform infrared spectroscopy (FTIR-ATR) on the formulation at the initial time point (ASC T0) and after six months under accelerated stability conditions (ASC T6). Characteristic absorption bands corresponding to carbonyl, ether, and hydroxyl functional groups were observed, confirming the structural integrity of the lipid–polymeric components within the emulsifying system. Antioxidant activity was evaluated using DPPH and ABTS assays, with IC₅₀ values comparable to those of a commercially available cream. In the DPPH assay, ASC T6 exhibited IC₅₀ of 5744.8571 μg/mL, comparable to a commercial formulation (5641.1585 μg/mL). In the ABTS assay, ASC T0 demonstrated antioxidant activity statistically equivalent (p > 0.05) to that of the commercial cream, with IC₅₀ values of 410.2358 and 420.2202 μg/mL, respectively. In conclusion, the preservation of antioxidant activity is attributed to the structural integrity of the formulated system, which stabilized and retained synergistic interactions of the antioxidants. Future studies should explore the incorporation of additional antioxidants and include in vivo instrumental assessments of stability and efficacy. Full article

Soil and water bioengineering (SWBE) is increasingly used as a nature-based solution for riverbank stabilization and riparian restoration, yet its effectiveness in tropical environments remains constrained by limited field-based evidence of species performance under hydrological disturbance. This study evaluated the establishment success and ecological effectiveness of four native riparian species (Croton urucurana Baill., Sesbania virgata (Cav.) Pers., Iochroma arborescens (L.) J.M.H.Shaw, and Gymnanthes schottiana Müll.Arg.) installed as live cuttings on a riprap structure exposed to recurrent flooding along the Paraopeba River, Brazil. A total of 160 live cuttings were monitored over a 33-month establishment period to assess survival, structural development, spontaneous vegetation recruitment, and changes in soil chemical properties and soil organic carbon stocks. Flooding acted as a dominant ecological filter, causing substantial early mortality, with overall survival declining sharply during a 70-day inundation period that included 58 consecutive days of submergence. Croton urucurana exhibited the highest survival and structural development, reaching median heights exceeding 5 m and cumulative shoot diameters greater than 100 mm after 33 months, whereas Gymnanthes schottiana showed complete mortality within the first year. Vegetation establishment facilitated spontaneous recruitment of native woody species, with 22 individuals recorded in planted sections compared to only 3 in adjacent non-planted areas. Soil organic carbon stocks increased from 38.9 to 60.6 Mg C ha⁻¹ in the 0–40 cm soil profile, indicating rapid soil development. These results demonstrate that SWBE interventions can simultaneously promote riverbank stabilization, vegetation recovery, and soil carbon accumulation. By providing quantitative field-based evidence under realistic hydrological disturbance conditions, this study advances the understanding of species selection and the ecological effectiveness of SWBE interventions in tropical riparian ecosystems. Full article

The integration of sedimentological and micropaleontological data in the Zanclean and Gelasian shallow-marine deposits of the Crotone Basin (southern Italy) has allowed documentation of meter-to-decameter-scale high-frequency sequences bounded by wave-ravinement surfaces (WRSs), which in turn are composed of meter-scale sedimentological cycles, referred to as bedsets. In contrast to high-frequency sequences, bedsets have a more subtle appearance, and their boundaries exhibit limited lateral extent compared to WRSs. Moreover, the micropaleontological analyses have allowed the definition of three parameters: distal/proximal (D/P: ratio between distal and proximal benthic foraminifera); fragmentation (Fr: percentage of fragmentation of benthic foraminifera); and P/B (ratio between planktonic and benthic foraminifera). In particular, the D/P and Fr allow to recognize uncertainty intervals containing the maximum flooding surface (MFS) of high-frequency sequences, whereas the P/B documents water-depth changes. Unlike in high-frequency sequences, the D/P, Fr and P/B parameters usually do not show appreciable variations associated with bedsets, confirming that the latter are unrelated to shoreline shifts and water-depth variations, but are rather controlled by minor sediment supply and/or wave regime changes. However, in rare cases, the micropaleontological parameters seem to indicate that subtle transgressive-regressive trends and water-depth variations can also be associated with bedset deposition, alluding to a ‘grey area’ of transition between high-frequency sequences of very small scale and bedsets. Further research is, therefore, needed to constrain the boundary between sedimentology and stratigraphy. Full article

Antimicrobial resistance is a major global health concern, intensified by the misuse of antibiotics and the lack of new effective treatments. Bacteria capable of forming biofilms exhibit increased resistance, making infections more difficult to treat. This study evaluated the essential oil from Croton pluriglandulosus leaves (OCp) for its antibacterial and antibiofilm properties. The essential oil, obtained by hydrodistillation and analyzed by GC-MS, contained eucalyptol (24.11%), spathulenol (16.90%), α-pinene (11.76%), and caryophyllene oxide (10.07%) as main constituents. Antibacterial activity was determined by Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC), with inhibition observed only for Staphylococcus aureus (MIC 10 mg/mL; MBC 5 mg/mL). OCp reduced biofilm biomass and CFUs in most strains, particularly in S. aureus and Escherichia coli. Scanning Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM) showed membrane damage in treated cells. Overall, OCp displayed promising antibacterial and antibiofilm potential, representing the first report of such activity for this essential oil. Full article

The Croton genus includes a diverse group of plants with remarkable potential in natural products research, particularly due to their bioactive compounds with hypoglycemic and phytochemical significance. This study examines Croton guatemalensis Lotsy, focusing on its chemical composition and its biological efficacy as a glucose-6-phosphatase inhibitor. Phytochemical analysis led to the isolation and structural elucidation of eleven compounds (1–11), including three new ent−clerodane diterpenes, designated crotoguatenoic acids C (9), D (10), and E (11). The absolute configurations of compounds 9–11 were determined by electronic circular dichroism (ECD) as (5R,8R,9R,10S)-configured ent–clerodanes. High-performance liquid chromatography–mass spectrometry (HPLC–MS/MS) revealed 25 peaks tentatively assigned to terpenoids, flavonoids, and alkaloids, highlighting the species’ chemical diversity. In vitro assays using ethanol–water extract (EWE) and isolated compounds with rat liver microsomes demonstrated inhibitory activity against glucose-6-phosphatase (G6Pase), particularly among ent–clerodane diterpenes (73–96%), with EWE and compounds 1, 4, and 11 showing the highest inhibition. Molecular docking analysis revealed strong interactions between these diterpenoids and the G6PC1 binding pocket, with binding energies comparable to chlorogenic acid (positive control). These findings position C. guatemalensis as a valuable source of bioactive diterpenoids and support the potential of ent-clerodane derivatives as natural G6Pase inhibitors for hyperglycemia management. Full article

The Sumaco volcano in Ecuador, which has a distinct geological origin from the Andes and is located in the Amazon basin, offers an opportunity to study untouched microbiomes. We explored comparative patterns of abundance from predicted functional profiling in soil samples collected along the elevation and sulfur gradients on its slopes. Using 16S rRNA gene metabarcoding, we inferred metagenome functional profiles, contrasting sample groups by altitude or soil sulfur concentration. We inferred that high-altitude communities may have higher predicted abundance for anaerobic metabolism (crotonate fermentation), coenzyme B12 synthesis, and degradation of diverse carbon sources (sugars and octane). High-sulfur soils were associated with an inferred enrichment of pathways for degrading complex organic compounds and nitrogen metabolism, reflecting adaptation to unique geochemical conditions. In contrast, low-sulfur soils are consistent with a higher predicted abundance of glycerol degradation. Within the limitation imposed by the potential weak associations of the applied predicted functional profiling to actual gene content, we propose that the inferred metabolic changes represent different ecological strategies for resource acquisition, energy generation, and stress tolerance, and they are optimized for varying conditions in this unique volcanic ecosystem. Our findings highlight how environmental gradients shape soil microbiome functional diversity and offer insights into microbial adaptation in Sumaco’s exceptional geochemistry within the Amazon. Further efforts linking functional predictions back to specific taxa will offer a complete ecological perspective of the microbiome exploration in the Sumaco volcano. Full article

Gastrointestinal disorders negatively affect populations worldwide. Considering the side effects of synthetic drugs, natural products can be a safe and effective alternative to help treat gastric ulcers and diarrhea. In this context, the present study reviewed the antiulcerogenic and antidiarrheal activities of species of the genus Croton (Euphorbiaceae). The scientific documents were retrieved from different databases, covering publications from the first report on the topic in 1998 to October 2025. Although the genus Croton comprises approximately 1200 species, only 11 have been evaluated for their antiulcerogenic and antidiarrheal potential in in vivo and in vitro studies. Among the identified bioactive constituents, the diterpenes trans-dehydrocrotonin and trans-crotonin, isolated from Croton cajucara, demonstrated significant antiulcerogenic activity in several experimental models in vivo. Similarly, the compound crofelemer, isolated from the latex of the bark of Croton lechleri, has shown promising results in several clinical trials for the treatment of diarrhea. Furthermore, flavonoids including rutin and quercitrin have been detected in Croton campestris. Regarding gastroprotective mechanisms, evidence suggests that extracts and essential oils obtained from Croton species may act through the nitric oxide pathway, promoting an antiulcerogenic effect. Additional studies are needed to investigate the gastroprotective and antiulcerogenic potential of at least 17 Croton species used empirically in traditional medicine for the treatment of gastrointestinal disorders but still without scientific validation. Full article