Search Results (695)

Williams–Beuren Syndrome (WBS) is a rare neurodevelopmental disease caused by a microdeletion on chromosome 7 (7q11.23) and associated with behavioral disorders such as hypersociability, impaired visuospatial memory, anxiety, and motor disorders. The precise underlying neurobiological bases remain unknown. The CD mouse is a genetic model that reproduces the deletion found in WBS patients on the equivalent mouse locus. Taking into account that monoaminergic systems are known to modulate behaviors that are altered in WBS, we hypothesized that CD mice could present quantitative and qualitative changes in brain noradrenaline, dopamine, and serotonin systems compared to wild-type (WT) littermates. We sampled 10 brain regions in female mice for quantifying monoamines and related compounds by high-performance liquid chromatography coupled to electrochemical detection. We found a decrease in dopamine in the nucleus accumbens and serotonin and its metabolites in the hypothalamus. Using correlative approaches of tissue content across the brain, we found that the relationships between neurotransmitters or their metabolic ratios (metabolite/neurotransmitter) changed in CD compared to WT. Notably, compared to WT, the ratios in CD mice showed striatal correlations for the serotonin/dopamine systems interaction, and cortical, thalamic, and hypothalamic correlations for the noradrenaline/dopamine systems interaction. The data suggest specific alterations of monoaminergic systems across the brain that could sustain the abnormal behavioral responses displayed by CD mice. Full article

Background: Deficient mismatch repair rectal cancer represents approximately 10% of rectal malignancies and demonstrates exceptional responsiveness to immune checkpoint inhibitors, achieving unprecedented complete response rates approaching 100%. This creates a novel clinical dilemma: should patients achieving complete response undergo standard surgical resection or pursue organ preservation through watch-and-wait management? Methods: We conducted a comprehensive literature review of clinical trials and retrospective studies published through 2025, focusing on response assessment strategies, decision-making frameworks, oncological outcomes, and quality of life assessments. Results: Landmark studies demonstrated remarkable efficacy with dostarlimab achieving 100% clinical complete response, while surgical cohorts achieved 68–92% pathological complete response rates. Response assessment challenges included pseudoprogression and pseudoresidue phenomena that complicated conventional imaging interpretation and required specialised multimodal evaluation protocols. Comparative analyses suggest equivalent oncological outcomes between surgical and non-surgical approaches in complete responders, achieving 100% disease-free survival at 2–3 years across multiple studies. The watch-and-wait approach offered significant advantages by preserving organ integrity and avoiding surgical morbidity, including permanent colostomy (15.4%) and perioperative complications (19.3%). Conversely, surgical management provided distinct benefits through definitive tissue confirmation and anxiety relief from intensive surveillance requirements and potential recurrence concerns. Conclusions: The surgery versus watch-and-wait dilemma represents a choice between equally effective oncological approaches with different quality of life implications. Evidence supports individualised decision-making weighing functional preservation benefits against patient preferences and institutional capabilities in this evolving therapeutic landscape. Full article

Deeply implanted biomedical devices like leadless pacemakers require an antenna with minimal volume and high radiation efficiency to ensure reliable in-body communication and long operational time within the human body. This paper introduces a novel implantable antenna designed to significantly reduce the spatial requirements within an implantable capsule while maintaining high radiation efficiency in lossy media like heart tissue. The design principles of the proposed antenna are outlined, followed by antenna parameters and an equivalent circuit study that demonstrates how to fine-tune the antenna’s resonant frequency. The radiation characteristics of the antenna are thoroughly investigated, revealing a radiation efficiency of up to 28% at the Medical Implant Communication System (MICS) band and 56% at the 2.4 GHz ISM band. The transmission efficiency between two deeply implanted antennas within heart tissue has been improved by more than 15 dB compared to the current state of the art. The radiation and transmission performance of the proposed antennas has been validated through comprehensive simulations using anatomical human body models, phantom measurements, and in vivo animal experiments, confirming their superior radiation performance. Full article

Heavy metal contamination in soil poses significant ecological risks, particularly within agricultural and forest ecosystems. This study evaluates the bioaccumulation of heavy metals (Cr, Co, Ni, Cu, Zn, As, Mo, Pb) by the ground beetle Carabus coriaceus Linnaeus, 1758, across contrasting Croatian ecosystems, with a focus on the role of soil pH in shaping metal dynamics. Concentrations in soils (0–30 and 30–60 cm) and beetle tissues were measured using portable X-ray fluorescence (pXRF), which provides total concentrations; inferences on bioavailability were based on soil properties such as pH and organic matter. Orchard soils showed higher Cu (49.9 mg/kg), Mo (10.3 mg/kg), and Ni (32.5 mg/kg), whereas forest soils contained elevated Zn (105.6 mg/kg), Pb (84.5 mg/kg), As (29.7 mg/kg), and Co (16.3 mg/kg). Beetles accumulated up to 481.0 mg/kg Zn at the orchard and 90.0 mg/kg Cu at the forest site. Bioaccumulation factors exceeded 1.0 for Co, Cu, and Zn, with particularly high values for Zn (2.20–5.75) suggesting both site-specific availability and possible physiological regulation. Soil and beetle analyses were complementary rather than equivalent: soils indicated total load, while beetles reflected biologically relevant fractions. C. coriaceus, therefore, represents a sensitive bioindicator, suitable for biodiversity-based soil contamination monitoring. Full article

Microplastic and nanoplastic (MNP) particles have been observed in various human organs. However, polypropylene (PP), one of the top three most commonly detected types of MNPs in terms of quantity, is also present in injections given for the infusion treatment of diseases, and there is a considerable knowledge gap concerning its adverse effects on the human cardiovascular system. In this study, we used commercial PP particles (500 nm), similar in size to nanoplastics (NPs) present in injections and greater than or equal in concentration to NPs in the blood of healthy individuals, as the experimental dose to study their toxicological effects on human umbilical vein endothelial cells. The results revealed that PP particles at 35 μg/mL, equivalent to 20 times the concentration of blood, reduced cell viability, induced oxidative stress, caused cytomembrane damage, increased the inflammatory response, promoted apoptosis, and inhibited cell migration and wound tissue healing. In addition, a NP concentration of up to 210 μg/mL decreased the level of zonula occludens-1. In conclusion, since we used spherical particles, a type of nanoplastic present in plastic-bottle injections in clinical treatment that induces toxicological effects, this study provides cellular-level insights into the ecological risks of NP exposure in the human body. Full article

Nitric esters are among the compounds that can liberate nitrogen monoxide (NO) in the organism. Due to the vasodilatation caused by nitrogen monoxide, NO-donors have been shown to protect endothelial function, acting as vasodilators, promoting efficient oxygen supply to tissues, to lower blood pressure, and to inhibit platelet aggregation. Incorporation of a NO-liberating moiety in the structure of non-steroidal anti-inflammatory drugs results in anti-inflammatory agents that are safer for the gastrointestinal system. In this research, ibuprofen and naproxen, two commonly applied non-steroidal anti-inflammatory drugs (NSAID), non-selective inhibitors of cyclooxygenases, were used to design novel anti-inflammatory agents able to release NO in the organism. Thus, the NSAIDs were amidated with beta-alanine and L-proline, which were able to incorporate the 2-nitro-oxyethyl moiety as the NO donor. The resulting compounds were anti-inflammatory agents, found to be more potent than the mother drugs, demonstrating remarkable inhibition of cyclooxygenase-2 over cyclooxygenase-1 and the ability to release NO in vitro. Furthermore, two of the most active anti-inflammatory compounds proved to be effective hypolipidemic agents, decreasing plasma total cholesterol, triglycerides, and LDL-cholesterol in hyperlipidemic rats significantly. The most effective compound in all the above tests was the ibuprofen derivative 5, which inhibited COX-2 by 95%, decreased inflammation by 73%, and reduced all lipidemic indices by more than 50%. Furthermore, docking experiments of compound 5 on the active sites of COX-1 and COX-2 showed that it interacts intensely with the binding site of COX-2, and the binding energy is equivalent to that of the relevant to celecoxib selective COX-2 inhibitor 4-[5-(4-bromophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (SC-5580). In conclusion, the performed structural modifications resulted not only in the improvement of the anti-inflammatory activity, compared with the parent NSAID, but also acquired strong hypolipidemic activity. Thus, the combination of structural characteristics resulting in a decrease in lipidemia, with possible inhibition of atherosclerosis, due to their anti-inflammatory activity and vasodilatation ability, via the liberated NO, may constitute a useful rationale for new compounds. Full article

Isorhapontigenin (trans-3,5,4′-trihydroxy-3′-methoxystilbene; ISO), a dietary derivative of resveratrol (trans-3,5,4′-trihydroxystilbene; RES), exhibits diverse health-promoting properties. To facilitate its potential development as a nutraceutical, a simple and reliable high-performance liquid chromatography (HPLC) method was developed and validated for the quantification of ISO in various murine biological matrices. Chromatographic separation was achieved with a reversed-phase HPLC column through a 17 min gradient delivery of a mixture of acetonitrile and formic acid (0.1% v/v) at a flow rate of 1.5 mL/min at 50 °C. Quantification was performed using ultraviolet (UV) detection at 325 nm, with a lower limit of quantification (LLOQ) of 15 ng/mL in both plasma and tissue homogenate samples. The method demonstrated excellent selectivity, accuracy, and precision, and ISO remained stable under the tested conditions. This method was subsequently employed to investigate the tissue distribution of ISO in mice following oral administration at a dose of 200 µmol/kg (equivalent to 51.7 mg/kg). ISO was rapidly absorbed and extensively distributed across major pharmacologically relevant organs. Despite its limited aqueous solubility, its oral absorption was not significantly compromised. Given its oral bioavailability and broad tissue distribution, ISO represents a promising candidate for further nutraceutical development. Full article

Abnormal skin pigmentation can cause significant esthetic concerns and impact quality of life. As melanin determines pigmentation, melanogenesis is a key target to manage pigmentation disorders. This study investigated the effects of extracts from the rhizome of Iris ×germanica L. var. florentina Dykes (often called Iris florentina L.) on melanogenesis. Active phytochemicals were identified by combining LC-MS-MS metabolic profiling with subsequent bioassay-directed fractionation of chromatographic eluent collected into 96-well plates. Fractions 41–43 increased melanin and contained germanaism B, providing evidence that it is a melanogenesis stimulator. In contrast, fractions 90–93 reduced melanin and contained iriflorental and iripallidal, identified as prospective melanogenesis inhibitors. To explore extract-based applications, the plant was subjected to ethanolic, chloroform, and supercritical carbon dioxide (SC-CO₂) extractions and tested in skin equivalent tissues. The ethanolic extract (rich in germanaism B) increased pigmentation, while the chloroform extract (higher in iriflorental and iripallidal) decreased it. The SC-CO₂ extract, with minimal germanaism B and enriched iriflorental and iripallidal, showed stronger depigmenting effect. This study is the first to report that rhizome of I. florentina contains phytochemicals with opposing effects on melanogenesis. Through different extraction processes, targeted extracts from a single botanical can address both hyper- and hypopigmentation, offering a novel approach to pigmentation modulation. Full article

Background and Objectives: The term “oncoplastic breast surgery” (OBS) incorporates plastic and oncologic concepts. Through the application of diverse mammoplasty approaches, the remaining breast tissue can be reconstructed, thereby enabling more extensive resections to be achieved with oncologically safe, margin-free outcomes. This study aims to assess the efficacy of the single incision lateral mammoplasty (SILM) technique as an oncoplastic approach for managing breast cancer located in the outer quadrant, in comparison with the matrix rotation flap (MRF) technique. Materials and Methods: This prospective randomized controlled study comprised 68 patients, who were randomized into two groups scheduled to undergo breast surgery: Group A constitutes the matrix rotation flap MRF group and Group B represents the single incision lateral sulcus mammoplasty (SLIM) group. A follow-up was planned for postoperative complications and esthetic outcomes. Results: The mean age of patients in Group A was 51.4 ± 9.4 years, compared with 52.6 ± 8.1 years in Group B. A total of 14.7% and 11.8% of patients in Group A reported a hematoma or seroma, respectively, which were higher than what was reported in Group B, where a hematoma and seroma were reported in 5.9% of patients. Additionally, 32.4% and 50% of patients in Groups A and B, respectively, reported excellent satisfaction. The evaluation with the Vancouver Scar Scale (VSS) revealed that esthetic outcomes were significantly better in Group B. Conclusions: Compared to the MRF procedure, the SLIM results in a much lower rate of postoperative hematoma, minor seroma, minimum blood loss, reduced areolar deviation, and improved breast symmetry. Both the MRF and SLIM techniques yield acceptable cosmetic outcomes. However, a longer-term follow-up is necessary to establish the definitive oncological equivalence between techniques. Full article

Background/Objectives: The use of collagen-based scaffolds in dentition tissue engineering has gained significance and importance in the field as they are structurally equivalent and biologically compatible with the native extracellular matrix (ECM). In this review, collagen-composite scaffolds for pulp, alveolar bone, and periodontal regeneration are analyzed in terms of materials, fabrication techniques, and clinical outcomes. Methods: Recent developments in collagen scaffolds are highlighted in this review, with a focus on type I collagen due to its structural strength and arginine–glycine–aspartic acid (RGD) motifs, which promote cell adhesion and differentiation. Composite materials, freeze-drying, electrospinning, and 3D bioprinting, which are used to improve the functionality of the scaffold, are key developments. Results: This review shows progress in collagen-based scaffolds for restoring dental tissues, such as dentin, gingival tissue, or bone, in humans. Electrospinning and 3D bioprinting are new manufacturing techniques that enhance the functionality of scaffold devices, and incorporating bioactive molecules increases the regenerative capacity; however, stability and long-term efficacy are still problems. Conclusions: Although they have a lot of potential, collagen-composite scaffolds face challenges like rapid degradation and limited mechanical strength. To make long-lasting, tailored dental regeneration therapies feasible, future research needs to improve smart biomaterials, gene delivery, and personalized designs for dental regenerative therapy. Full article

Additive manufacturing technology, specifically material extrusion, offers great potential for scaffold manufacturing in tissue engineering. This study presents a novel methodology for the design and optimization of 3D printed polymeric scaffolds to enhance cell viability, thereby promoting improved cell proliferation for tissue engineering applications. Different infill patterns, including gyroid, parallel sinusoidal, and symmetric sinusoidal, were evaluated to determine their impact on cell proliferation and tissue regeneration. To overcome the limitations of existing slicer software, a novel open-source software called FullControl GCode Designer was utilized, enabling the creation of customized infill patterns without restrictions. VOLCO software was employed to generate voxelized 3D models of the scaffolds, simulating the material extrusion process. Finite element analysis was conducted using Abaqus software to evaluate the mechanical properties of the different designs. Additionally, new scripts were developed to evaluate the interconnectivity and pore size of the voxelized models. A factorial design of experiments and a genetic algorithm (combined with Kriging metamodels) were applied to identify the optimal configuration based on optimization criteria (keeping the mechanical stiffness and pore size within the recommended values for trabecular bone and maximizing the surface and interconnectivity). Biological testing was conducted on polylactic acid scaffolds to preliminarily validate the effectiveness of the modeling and optimization methodologies in this regard. The results demonstrated the agreement between the optimization methodology and the biological test since the optimum in both cases was a symmetric sinusoidal pattern design with a configuration resulting in a structure with 53.08% porosity and an equivalent pore size of 584 µm. Therefore, this outcome validates the proposed methodologies, emphasizing the role of pore surface area and interconnectivity in supporting cell proliferation. Overall, this research contributes to the advancement of AM technology in tissue engineering and paves the way for further optimization studies in scaffold design. Full article

Liver fibrosis remains difficult to treat, in part because many hepatoprotective triterpenoids suffer from poor oral bioavailability and lack of optimized delivery formats. Ganoderma amboinense is a rare “antler” reishi species long valued in Eastern traditions yet scarcely studied for its phytochemical and pharmacological potential. Here, we report the first investigation of an ethanol-extracted G. amboinense sublingual dripping pill formulation (GDP) in a carbon-tetrachloride (CCl₄)–induced mouse model of liver fibrosis. Mice treated with GDP at one- and five-times the human equivalent dose were compared to groups receiving unprocessed G. amboinense powder (GP) or purified ganoderic acid A (GA-A). GDP significantly prevented CCl₄-induced weight loss and hepatomegaly, normalizing liver-to-body weight ratios and serum AST/ALT activities (p < 0.05). Histological evaluation showed that GDP markedly reduced hepatocellular necrosis and collagen deposition, restoring tissue architecture. Furthermore, GDP suppressed hepatic expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, COX-2) and profibrotic markers (TGF-β1, CTGF, α-SMA) to levels comparable with or superior to GA-A. These results demonstrate that a dripping pill dosage form can effectively deliver G. amboinense triterpenoids and unlock their hepatoprotective activity, supporting further development of GDP as a novel liver-support nutraceutical. Full article

Tenecteplase (TNK), a genetically modified tissue plasminogen activator, has emerged as a promising alternative to alteplase (ALT) for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Our aim was to synthesize the current clinical evidence on TNK use in AIS patients, comparing efficacy, safety, and workflow benefits to ALT. A narrative review was conducted by searching PubMed and Scopus (January 2024–March 2025) for studies comparing TNK and ALT in AIS. A total of 35 eligible papers were included. Data were grouped by treatment scenario: IVT-only, bridging before endovascular therapy (EVT), and intra-arterial thrombolysis (IAT). The results showed that TNK is non-inferior—and in some analyses, superior—to ALT regarding functional outcomes, especially in large vessel occlusion. TNK facilitates shorter treatment delays due to its single-bolus administration. While some trials report higher rates of intracranial hemorrhage, overall safety and mortality are comparable. In conclusion, TNK appears to exert equivalent or superior efficacy and safety compared to ALT in multiple AIS scenarios. Its pharmacological and logistical advantages support its broader clinical adoption. Further trials are needed, especially for IAT, central retinal artery occlusion, and patients on dabigatran. Full article

Autologous fat grafting of human lipoaspirate (LA) is increasingly used in reconstructive and cosmetic surgery for lipofilling and stem cell-rich “nanofat” reinjection for regenerative medicine. While commercial devices (e.g., REVOLVE and Puregraft) are available, many surgeons use non-standardized manual washing techniques, leading to inconsistent graft retention (20–80%). Moreover, no system can unite washing directly with mechanical processing to produce a nanofat-like product directly from raw LA. We developed a novel preparation device (PD) that is designed for peristaltic pump-driven washing of LA and can be seamlessly combined with our previously developed Emulsification and Micronization Device (EMD) into an automated closed-loop platform. Human LA samples were washed with the PD and compared to standard manual washing via visual colorimetric analysis. We then evaluated the mechanical processing of PD-washed LA using our EMD and assessed cell count, viability, and stromal vascular fraction-derived subpopulations (i.e., mesenchymal stem cells, endothelial progenitor cells (EPCs), pericytes, transit-amplifying (TA) progenitor cells, and supra-adventitial adipose stromal cells). Recirculating LA through the PD for at least one minute resulted in sufficient mixing, producing LA with equivalent color and quality to manual washing. Integrating the EMD within a platform enabled both washing and mechanical processing under peristaltic flow, enriching key subpopulations compared to manual methods. Thus, our fluidic platform effectively washes LA in a closed-loop system, minimizing LA tissue manipulation and opportunity for contamination while also simplifying the workflow for mechanical processing. Further refinement and automation of this platform would enhance the reproducibility and quality of small-volume fat grafts, cell-assisted lipotransfer, and stem/progenitor cell injections to promote wound healing and angiogenesis. Full article

Objective: The objective of this study was to compare the performance and robustness of a deep learning reconstruction method against established alternatives for soft tissue CT image reconstruction. Materials and Methods: Images were generated from portal venous phase chest–abdomen–pelvis CT scans (n = 99) acquired on a dual-layer spectral detector CT using filtered back projection, iterative model reconstruction (IMR), and deep learning reconstruction (DLR) with three parameter settings, namely ‘standard’, ‘sharper’, and ‘smoother’. Experienced raters performed a quantitative assessment by considering attenuation stability and image noise levels in ten representative structures across all reconstruction methods, as well as a qualitative assessment using a four-point Likert scale (1 = poor, 2 = fair, 3 = good, 4 = excellent) for their overall perception of ‘smoother’ DLR and IMR images. One scan was excluded due to cachexia, which limited the quantitative measurements. Results: The inter-rater reliability for quantitative measurements ranged from moderate to excellent (r = 0.63–0.96). Attenuation values did not differ significantly between reconstruction methods except for DLR against IMR in the psoas muscle (mean + 3.0 HU, p < 0.001). Image noise levels differed significantly between reconstruction methods for all structures (all p < 0.001) and were lower than FBP with any DLR parameter setting. Image noise levels with ‘smoother’ DLR were predominantly lower than or equal to IMR, while they were higher with ‘standard’ DLR and ‘sharper’ DLR. The ‘smoother’ DLR images received a higher mean rating for overall image quality than the IMR images (3.7 vs. 2.3, p < 0.001). Conclusions: ‘Smoother’ DLR images were perceived by experienced readers as having improved quality compared to FBP and IMR while also exhibiting objectively lower or equivalent noise levels. Full article