Combining the Salt‐Tolerant Plants Limonium algarvense Erben and Polygonum maritimum L. Promotes Synergistic Bioactivities for Enhanced Cosmetic Applications

ABSTRACT The demand for natural and sustainable ingredients in dermo‐cosmetic formulations has promoted the use of coastal salt‐tolerant plants as novel bioresources. This study evaluated aqueous extracts of Limonium algarvense and Polygonum maritimum , two salt‐tolerant coastal plants and their mixtures (3:1, 1:1, 1:3, w/w) for antioxidant, metal‐chelating, enzyme‐inhibitory, antimicrobial and cytotoxic properties. Chemical profiling revealed diverse phenolic signatures dominated by catechin, myricetin and quercetin derivatives, which are known contributors to antioxidant and enzyme‐modulating activity. L. algarvense showed the strongest superoxide‐scavenging activity (EC 50  = 219 µg/mL), while P. maritimum was the most effective hyaluronidase inhibitor (EC 50  = 42.9 µg/mL). The 1:3 mixture displayed the most pronounced synergistic behaviour, notably in hydroxyl‐radical scavenging (EC 50  = 62.7 µg/mL; SE = 0.08) and antibacterial activity against Escherichia coli (MIC = 39.68 µg/mL; SE = 0.31). The 3:1 mixture showed enhanced elastase inhibition (EC 50  = 33.0 µg/mL; SE = 0.76) and increased copper‐chelating capacity (EC 50  = 533 µg/mL, SE = 0.52). All extracts maintained cell viability above 90%, supporting their safety for topical applications. Together, these results indicate that L. algarvense and P. maritimum deliver complementary and synergistic activities relevant to dermo‐cosmetic innovation, emphasising their potential as sustainable, multifunctional ingredients compatible with saline agriculture and low‐freshwater production systems.

Isoflavonoids and Epigenetic Modulation: Therapeutic Insights for Cancer Treatment

ABSTRACT Isolavonoides represent the second largest subgroup of flavonoids and have an influence on critical molecular pathways and restore cellular homeostasis, through the reprogramming of epigenetic regulatory mechanisms. This feature indicates a crucial therapeutic potential that could be better explored to attend cancer treatment. Isoflavonoids, acting as epigenetic modulators, could contribute to the development of new therapeutic approaches in cancer, especially in onco‐hematological diseases. Pterocarpans are a subgroup of isoflavonoids that have been extensively studied for their biological properties. The molecule (+)‐2,3,9‐trimethoxypterocarpan demonstrates high gastrointestinal (GI) absorption and the ability to cross the blood–brain barrier (BBB) in silico without violating Lipinski's rule, making it a desirable candidate in leukemia treatment. The synthesis of this molecule dates back more than a decade. In silico models, such as SwissADME, corroborate the notion of good intestinal absorption and the ability to cross the BBB. Also, it is suggested that P‐glycoprotein is a substrate, which is related to its potential for active efflux from both the BBB and GI. This review highlights the biological mechanisms of this class of natural products from a translational perspective, emphasizing their chemical properties and epigenetic biological activities, which offer new therapeutic perspectives, particularly in oncology.

Erucastrum virgatum subsp. virgatum (Brassicaceae) Endemic to Sicily (Italy): Biological Properties and Phenolic Content of Leaf Extracts

ABSTRACT The present work reports a comparative study between extracts obtained by different methods (ultrasonic bath‐assisted extraction, maceration, decoction, and Soxhlet extraction) from the leaves of Erucastrum virgatum subsp. virgatum collected in Sicily (Italy), using ethanol and water as “green” solvents. All the extracts were found to be nontoxic after preliminary toxicity evaluation by the Artemia salina lethality bioassay. The antioxidant properties of the extracts were investigated by in vitro methods based on diverse mechanisms. All the extracts showed moderate radical scavenging activity in the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) test and mild reducing power, with 70% ethanol extracts exhibiting better activity than aqueous ones. Conversely, all the aqueous extracts showed stronger chelating activity than that of the 70% ethanol ones. Weak antimicrobial properties against selected Gram‐positive and Gram‐negative bacteria were observed only for 70% ethanol extracts. The results of the spectrophotometric determinations highlighted higher total polyphenol and flavonoid contents for all the 70% ethanol extracts compared to the aqueous ones. Furthermore, the phenolic profile of the most promising extracts was characterized by HPLC‐PDA/ESI‐MS analysis.

Cytogenotoxic Effects and Physicochemical and Molecular Profiles of Eugenol‐Derived Triazoles With Phytotoxic Potential

ABSTRACT Eight eugenol‐derived 1,2,3‐triazole derivatives ( 2a–2h ) were evaluated for their phytotoxic and cytogenotoxic activities. Bioassays were performed using Lactuca sativa to assess macroscopic parameters, including germination percentage, germination speed index, and root growth (RG), as well as microscopic parameters, such as the mitotic index (MI) and chromosomal alteration (CA) and nuclear alteration (NA). Compounds 2b and 2e , bearing ortho ‐bromine and meta ‐chlorine substituents, respectively, exhibited the highest phytotoxic activity, with effects comparable to glyphosate. In contrast, 2c , 2d , 2f , 2g , and 2h , which contain other halogens and different aromatic patterns, stimulated RG. Cytogenetic analysis revealed that 2b and 2e significantly reduced the MI and increased NA and CA, indicating cytotoxic and genotoxic potential. Theoretical calculations of physicochemical properties showed that 2b , 2e , and 2g are hydrophilic. In contrast, the others are lipophilic, a feature that may influence their interaction with plant tissues and help explain the observed differences. Compared with glyphosate, the compounds 2b and 2e exhibited a variety of intermolecular interactions due to their hydrophilic behavior, resulting in lower docking energy and surpassing the quality and quantity of interactions observed with glyphosate itself. These findings highlight 2b and 2e as promising candidates for the development of herbicides with alternative modes of action.

Europium Metal Complex [Eu(dbm) 3 .LAP] Promotes Antinociceptive Behavior via TRPA1 Neuromodulation and an Anti‐Inflammatory Effect in Adult Zebrafish

ABSTRACT The identification of antinociceptive compounds often relies on animal models such as zebrafish, in which TRPA1 activation induces hyperlocomotion. This study presents the first evaluation of the anti‐inflammatory and antinociceptive properties of the europium complex [Eu(dbm) 3 .LAP], derived from Lapachol, and investigates its possible interaction with the TRPA1 channel in adult zebrafish. The complex was administered intramuscularly, and its effects were compared with camphor and morphine controls. In vivo findings were integrated with in silico docking, molecular dynamics simulations, and predictive pharmacokinetic analysis. Eu(dbm) 3 .LAP (40 mg/kg, oral) was effective specifically in the inflammatory phase, and its effect was blocked by camphor, indicating TRPA1 modulation. The compound also reduced carrageenan‐induced inflammation and attenuated oxidative stress in nerve and liver tissues. In silico predictions indicated high intestinal absorption (∼100%), good blood–brain permeability (LogBB = 0.62), and low cardiotoxicity (pKi hERG = 7.73). Docking revealed a binding energy of −8.1 kcal·mol − 1 with stable interactions involving LYS1046, TYR1049, and LYS1052. Molecular dynamics confirmed stability over 100 ns and preservation of key hydrogen bonds, supporting the modulatory potential observed in vivo.

Continuous Precipitation of Biotherapeutics: A Review

Abstract The increasing efficiency of upstream production of biotherapeutics exposes significant challenges in downstream purification. Chromatography, the traditional gold standard, offers high purity and yield but faces limitations such as restricted mass transfer, limited capacity, and scalability issues, especially with high‐titer strains. As biomanufacturing moves toward fully continuous production, interest grows in alternatives beyond chromatography. Precipitation has emerged as a versatile, scalable, and titer‐independent technique that achieves yields and purities comparable to chromatography while offering simpler and more adaptable processing. It can be operated continuously, enabling seamless bioprocessing. Despite its potential, continuous precipitation remains less explored for biotherapeutics due to biomolecular complexity. Effective design requires deep understanding of thermodynamics, process modeling, hardware, and real‐time monitoring. This review discusses these critical factors, key design elements, and application examples, highlighting precipitation as a promising purification technology and exploring future research directions.

Strongyloides Antigens Alter Cytokines Responses in Toxoplasma gondii ‐Infected BeWo Trophoblast Cells

ABSTRACT The importance of co‐infections is not yet completely understood, and the impact and direction of their effects vary considerably. This study aimed to evaluate the role of total saline extract (TS) and excretory/secretory (ES) products of Strongyloides venezuelensis filarioid larvae on a maternal‐interface cell model during Toxoplasma gondii infection. BeWo cells were cultured and stimulated with TS antigens and ES products to evaluate their effects on cell viability, T. gondii proliferation, and cytokine production. Both TS and ES had no impact on BeWo cell viability and T. gondii proliferation. However, stimulation with the highest concentration of TS resulted in increased IL‐4 production. Additionally, IL‐6 levels significantly increased after T. gondii infection in all ES‐treated conditions. Increased IL‐4 and IL‐6 production was observed in comparison to the untreated control group (C) and/or between infected and uninfected cells under the same antigenic stimulation. Moreover, MIF levels increased consistently after T. gondii infection, regardless whether antigenic stimulation was present. Our results show that S. venezuelensis antigens can influence the host immune environment, altering the secretion profile of IL‐4 and IL‐6 in BeWo cells, thereby highlighting the complexity of the helminth and protozoan interaction. These studies are essential for a comprehensive understanding of responses in strongyloidiasis and their possible implications for T. gondii infection and disease control strategies.

The Minimum Age of Criminal Responsibility Internationally—History, Systems and the Future

ABSTRACT Background In most countries, a criminal conviction requires evidence that the individual committed the act and that they had the mental capacity to understand what they were doing and that it was wrong. Youth, as an indicator of brain development, is one factor affecting criminal capacity. Worldwide, this has commonly been managed in part by setting in law an age below which criminal incapacity is presumed, so no prosecution is possible. Considerable variation in the MACR was confirmed across 195 countries. Some countries have no MACR. Otherwise, the MACR ranges from 7 years (some African and South Asian countries) to 18 (some South American countries); many North Asian, European and a few African countries set theirs at 14 which is the most frequently found level, and also the minimum age recommended by the United Nations Convention on the Rights of the Child. Therefore, how do countries set or change their MACR? Aims To explore change, efforts to change and impact of change in MACR internationally. Methods Between February 1st 2022 and December 31st 2023, members of an international research group (GIRAF—Group of International Researchers in Adolescent Forensics) were asked to complete an emailed questionnaire about changes in the MACR, or efforts to change it, in their country since 2000. Reports were then collated, circulated and discussed within the group. Results Among the 14 countries responding in detail about the MACR, efforts to raise the MACR had been successful in three, but in nine such efforts had been unsuccessful; in at least two countries pressures were to lower their MACR, but in only one, Denmark, did that happen (from 15 to 14) in the data collection period (though this change was subsequently reversed). Factors most influencing retention of a lower age were exceptional individual cases, which triggered press and political interest in retaining a higher age, and well‐evidenced and developed arguments from legal, social and medical or other clinical bodies. Conclusions and Implications The wide differences in the MACR between countries suggest under‐use of evidence in deciding it. We need more governmental willingness to bring the MACR at least to the UN‐recommended level—but accompanied by research into the impact of this. Efforts targeted exclusively on child and adolescent welfare may have less effect if they also force children through the criminal justice system, with consequent impact on self‐identity and sense of citizenship. A low MACR is also likely to be more directly and indirectly costly than a higher one.

Conversion to Cardiac Surgery During Elective and Urgent Transcatheter Aortic Valve Implantation: A Systematic Review and Meta‐Analysis

ABSTRACT Transcatheter aortic valve implantation (TAVI) has become an established treatment for severe aortic stenosis. However, the need for unplanned conversion to cardiac surgery (CS) during TAVI remains an infrequent but critical event. It is unclear whether this risk is higher in patients undergoing urgent procedures. We conducted a systematic review and meta‐analysis to compare the incidence of unplanned conversion to CS between patients undergoing urgent versus elective TAVI. A systematic search of PubMed, SCOPUS, and Cochrane databases was performed to identify eligible studies. The primary outcome was the rate of unplanned conversion to CS. Secondary outcomes included mortality, device success, vascular complications, device embolization, acute kidney injury (AKI), stroke, permanent pacemaker implantation (PPI), moderate‐or‐severe paravalvular regurgitation (PVL), need for second valve implantation, bleeding, and duration of hospitalization. Seven studies comprising 71,909 patients were analyzed; 5108 underwent urgent TAVI and 66,801 underwent elective TAVI. No significant difference in conversion to CS was observed between the groups (RR: 0.89; 95% CI: 0.65−1.22). Device success rates were similar (RR: 0.99; 95% CI: 0.97–1.00). Urgent TAVI was associated with prolonged hospitalization (mean difference: 7.75 days; 95% CI: 4.06–11.45) and increased AKI risk (RR: 2.20; 95% CI: 1.53–3.16). Vascular complications, device embolization, stroke, PPI, PVL, second valve implantation, and major bleeding rates were comparable between the groups. Urgent TAVI is not associated with an increased risk of unplanned conversion to surgery. The observed higher AKI rates and longer hospital stay suggest that patient‐related factors beyond procedural urgency may contribute to adverse outcomes.

Vitamin D: The Overlooked Factor in Cardiovascular Disease Prevention