Search Results (6,554)

Background/Objectives: Visuomotor interception requires aligning action with the future state of moving targets under sensory and motor delays. This constraint provides a tractable framework to examine how predictive and feedback-driven processes interact. This narrative review evaluates theoretical and empirical accounts of interception, with emphasis on how prediction and online control are integrated across behavioral and neural levels. Methods: We conducted a narrative synthesis of behavioral, eye-tracking, computational, and neurophysiological studies on visuomotor interception. Literature was identified through searches of PubMed, Web of Science, and Google Scholar using search terms including “visuomotor interception,” “predictive motor control,” “eye–hand coordination,” “time-to-contact,” “sensorimotor delay,” and related combinations. Studies published between 1986 and 2026 were considered, with emphasis on peer-reviewed empirical and theoretical work. Preprints were included only when directly relevant and are identified as such. The review compares internal model, ecological, and hybrid frameworks, and organizes evidence around spatial (“where”) and temporal (“when”) components of control. Results: Across paradigms, interception behavior is not well accounted for by purely predictive or reactive mechanisms. Instead, trajectories reflect a continuous interaction between anticipatory guidance and online correction. Spatial and temporal components show partial dissociation across tasks and manipulations. Available evidence supports the involvement of distributed circuits, including parietal, frontal, cerebellar, and subcortical systems, while indicating that eye movements play an active role in both information sampling and motor planning. Conclusions: Interception is best understood as the product of interacting biological, environmental, and learned constraints. Similar behavioral signatures can arise from distinct mechanisms, arguing against a unitary account. Progress requires integrating behavioral analyses with model-based and neural approaches to dissociate underlying computations. Full article

Elastic fibers are key components of the skin extracellular matrix and are essential for maintaining skin integrity and elasticity. During skin aging, particularly photoaging, elastic fiber integrity is progressively compromised by increased elastase activity and the downregulation of elastin and scaffold-related gene expression. Therefore, effective strategies to preserve elastic fiber function should address not only elastin synthesis but also enzymatic degradation and scaffold integrity. In this study, we investigated a multitarget approach to restoring the elastic fiber network by modulating elastin production, elastase activity, and scaffold protein expression. We found that Copper Tripeptide-1 enhanced elastin expression and secretion, ethyl ferulate inhibited elastase activity, and cedrol promoted scaffold-related gene expression and microfibrillar protein restoration in dermal fibroblasts. To assess the biological relevance of this approach, the combined treatment was evaluated using UV-damaged human skin biopsy samples. This combination effectively mitigated UV-induced elastic fiber disruption and significantly improved fiber architecture, as confirmed by immunofluorescence staining and scanning electron microscopy. These findings indicate that coordinated modulation of elastin production, proteolytic protection, and scaffold reinforcement is essential for maintaining elastic fiber integrity and represents a promising approach for preserving skin elasticity during aging. Full article

The search for new anticancer agents with improved efficacy and reduced toxicity has intensified interest in metal-based compounds. In this study, two novel palladium(II) complexes, synthesized from Schiff base ligands derived from 5-chloro-salicylaldehyde and p-hydroxybenzylamine or tyramine, were chemically characterized and biologically evaluated. Both complexes exhibited significant cytotoxic activity against the MCF-7 breast cancer cell line in a dose- and time-dependent manner, with Pd2 showing slightly higher potency. Morphological analysis of treated cells indicated that apoptosis is the predominant mechanism of cell death. To gain deeper insight into the potential mechanisms underlying the observed anticancer activity, several biologically relevant targets were investigated. Enzyme kinetics revealed that the complexes act as uncompetitive inhibitors of liver catalase, suggesting a possible role in the induction of oxidative stress. Fluorescence studies demonstrated that Pd2 interacts with CT-DNA through combined intercalative and minor groove binding modes and exhibits significant binding affinity toward human serum albumin, predominantly at Sudlow’s site I. Molecular docking analysis further supported favorable interactions with catalase, estrogen receptor α, and B-form DNA, providing structural insight into the experimentally observed biological effects. Overall, the study explores multiple potential mechanisms of anticancer action, underscoring the promising therapeutic potential of these palladium(II) complexes, while antitumor activity has been initially assessed using a MCF-7 cell line as a preliminary model. Full article

Background/Objectives: In several contexts, Dried Sample Spot Devices (DSSDs) offer a convenient and safe alternative for sampling, storage, and shipment, allowing the transport and storage of biological samples at room temperature, reducing shipment costs and improving access to diagnostics in faraway sites. This can be pivotal for the use of the therapeutic drug monitoring of anti-HIV treatment: therefore, this study aimed to develop and validate a UHPLC–MS/MS method for the simultaneous quantification of 12 antiretroviral drugs, including the recently introduced long-acting agents, in Dry Plasma Spots (DPSs). Methods: First, 100 µL of plasma sample and 100 µL of internal standard solution were spotted on each DSSD. After complete drying, DPSs were added with an acidifying solution (ammonium acetate buffer pH 4), and then, each sample underwent extraction with hexane-dichloromethane 50:50 (v/v). After tumbling, the organic phase was evaporated and reconstituted for injection. An Acquity UPLC HSS T3 1.8 µm, 2.1 × 150 mm column at 50 °C enabled separation, performed using H₂O + F.A. 0.05% (phase A) and ACN + F.A. 0.05% (phase B) as the mobile phase in gradient elution mode, for a total run time of 15 min. Results: The method was validated over the clinically relevant concentration ranges. For all quality control levels, accuracies ranged from 98.2% to 114.1%, and intra-day and inter-day RSD values ranged from 2.7% to 9.7% and 5.2% to 13.9%, respectively. All analytes demonstrated satisfactory short- and long-term stability in DPSs, confirming the suitability of shipment and storage at room temperature. Conclusions: The method demonstrated robustness and reproducibility in accordance with FDA and EMA guidelines. It ensures satisfactory accuracy and rapid analysis, supporting its application in clinical practice, including for monitoring the newest long-acting drugs. Full article

Background/Objectives: Circulating tumour DNA (ctDNA) assays enable non-invasive assessment of tumour burden and treatment response in oncology. However, quantitative ctDNA outputs (such as variant allele frequency, tumour fraction, and aggregate burden scores) remain difficult to interpret and compare across platforms. This evidence-mapping review evaluates current quantitative reporting approaches in pancreatic ductal adenocarcinoma (PDAC) and examines the potential role of KRAS mutant ctDNA as a biologically grounded reference metric. Methods: A systematic literature search was conducted across PubMed/MEDLINE and Scopus to identify studies reporting quantitative ctDNA metrics in PDAC. Eligible studies included those measuring plasma KRAS mutations and/or reporting variant allele frequency, tumour fraction, or multi-locus aggregate metrics. Additional relevant primary studies identified through broader manual searching of PubMed were assessed against the same prespecified eligibility and classification criteria before inclusion. Data were synthesised narratively, focusing on reporting frameworks, units of measurement, assay characteristics, and the interpretability of quantitative outputs across platforms. Results: Substantial heterogeneity was observed in ctDNA quantification methods and reporting standards. Ratio-based metrics such as variant allele frequency and tumour fraction were commonly used but varied according to assay design, plasma input volume, and background cell-free DNA levels. Few studies reported absolute mutant molecule counts per unit volume. Given that approximately 90–95% of PDACs harbour truncal activating KRAS mutations, plasma KRAS was consistently represented across platforms and demonstrated potential as a shared quantitative anchor. Limited standardisation was noted in distinguishing detectability from quantifiability based on sampling depth and counting statistics. Conclusions: Current ctDNA reporting in PDAC lacks a shared quantitative reference, limiting cross-study comparability. Reporting KRAS mutant molecules per millilitre and adopting an assay-agnostic framework distinguishing detection from quantification may improve interpretability, support harmonisation across platforms, and facilitate cumulative learning in pancreatic cancer ctDNA research. Full article

Ozone layer depletion exacerbates UV-induced skin damage, including oxidative stress and DNA lesions, thereby increasing the risk of photoaging and malignant transformation. Natural extracts have gained increasing attention as a photoprotective ingredient in cosmeceutical products. Kaempferia galanga, a species in the Zingiberaceae family traditionally used for skin-related treatment and listed in the CosIng database, exhibits multiple biologically relevant properties; however, its anti-photoaging and anti-photo-senescence effects in human dermal fibroblasts remain unexplored. This study investigated the in vitro photoprotective effects of K. galanga extract against UVB-induced photoaging and cellular senescence in human dermal fibroblasts. The ethanolic extract of K. galanga rhizomes (EKGRs) contained ethyl p-methoxycinnamate (EPMC) as a major constituent (33.7 ± 3.7% (w/w) of the crude extract), identified by HPLC-UV. Additionally, EKGR exhibited significant protective effects in UVB-irradiated fibroblasts. EKGR showed no cytotoxicity at concentrations up to 50.0 µg/mL, as determined by the MTT assay. EKGR pretreatment significantly reduced UVB-induced cellular senescence in human dermal fibroblasts compared with UVB-exposed cells (22.2 ± 2.7% vs. 36.7 ± 8.0%). Furthermore, pretreatment with EKGR prior to UVB exposure resulted in a significant increase in pro-collagen type I production (37,075.1 ± 7532.2 pg/mL) and a concomitant decrease in MMP-1 secretion (25,754.1 ± 4042.0 pg/mL) relative to UVB-exposed cells (26,845.8 ± 1454.6 and 39,910.8 ± 6035.1 pg/mL, respectively). To demonstrate formulation feasibility, EKGR was incorporated into an oil-in-water microemulsion, which exhibited concentration-dependent SPF enhancement. Collectively, these findings demonstrate the photoprotective efficacy of EPMC-rich EKGR and highlight its potential as a cosmeceutical ingredient for mitigating UVB-induced photo-senescence and skin aging, with an additional SPF boosting effect. To our knowledge, this study provides the first evidence of EKGR-mediated protection against UVB-induced cellular senescence in human dermal fibroblasts. Full article

Background/Objectives: Natural compounds occupy a pharmacologically rich chemical space, characterized by abundant scaffolds, extensive functional group elaboration, and defined stereochemistry. In this context, Helichrysum italicum, a Mediterranean medicinal plant, represents a valuable source of polyphenols with multiple biological and pharmacological activities. Methods: Here, we introduce an inverse molecular docking fingerprint approach to systematically investigate eight major Helichrysum italicum polyphenols, including $\alpha$-pyrones (arzanol, ethylpyrone), flavonols (gnaphaliin, kaempferol, quercetin), and flavanones (naringenin, pinocembrin, hesperetin). More than 40,000 human protein structures from the Protein Data Bank were screened to generate target-based inverse docking score fingerprints for each compound. Results: Hierarchical clustering of these fingerprints revealed shared binding patterns among structurally related polyphenols and enabled hypothesis generation regarding potential synergistic effects. Notably, favorable interactions were identified with PPARG and CARM1, supporting therapeutic relevance in inflammation and cancer, alongside additional targets associated with neurodegeneration and bone metabolism. Conclusions: This study establishes inverse docking fingerprints as a robust, mechanism-oriented method for natural product research and highlights Helichrysum italicum polyphenols as starting points for medicinal chemistry and drug discovery. Full article

Punica granatum L. is a nutritionally relevant fruit with a complex phytochemical profile that varies across its anatomical fractions, including peel, arils, juice, seeds, and seed oil. Although pomegranate is widely recognized for its health-promoting potential, the nutritional significance of its matrix-dependent composition, bioavailability, and gut microbiota-mediated metabolism remains insufficiently integrated. This review aimed to critically evaluate the phytochemical diversity of pomegranate and its nutrition-related multi-target biological functions, with particular emphasis on food matrices, bioaccessibility, and translational relevance. A structured review of peer-reviewed studies indexed in major scientific databases from 2000 to January 2026 was conducted. Eligible reports included analytical, preclinical, and clinical studies addressing the composition of pomegranate-derived materials and their biological effects, with attention to extraction matrix, processing, bioavailability, microbial biotransformation, and mechanisms of action. Pomegranate exhibits marked matrix-specific phytochemical diversity. Peel is particularly rich in ellagitannins, especially punicalagin and punicalin; arils and juices are enriched in anthocyanins and flavonols; and seed oil contains high levels of punicic acid. Reported biological activities include antioxidant, anti-inflammatory, antimicrobial, metabolic, anti-aging, and anticancer effects. These actions appear to result from synergistic interactions among multiple bioactive compounds rather than from a single dominant constituent. Importantly, gut microbiota-driven conversion of ellagitannins and ellagic acid into urolithins is a major determinant of systemic bioactivity and may contribute to interindividual variability in response. The health effects of pomegranate should be interpreted within a nutrition-focused, matrix-dependent framework integrating composition, processing, bioavailability, and microbiota-derived metabolism. Full article

Titanium dental implants are widely regarded as the gold standard for the rehabilitation of missing teeth due to their high survival rates and favorable mechanical properties. However, in the oral environment, implant materials are continuously exposed to complex chemical, mechanical, and biological factors that may lead to surface degradation, including corrosion, tribocorrosion, and mechanical wear. These processes can alter implant surface characteristics and influence biological responses in peri-implant tissues. Zirconia implants have been introduced as alternative material due to their favorable aesthetics and biocompatibility. Nevertheless, zirconia ceramics are also susceptible to degradation phenomena, including hydrothermal aging, phase transformation, and surface wear under specific conditions, although their clinical relevance remains unclear. In addition, emerging hybrid titanium–zirconia implant systems introduce new considerations regarding surface stability. This scoping review, conducted in accordance with PRISMA-ScR guidelines, summarizes the current evidence on degradation mechanisms affecting titanium, zirconia, and hybrid dental implants, with particular focus on processes occurring in the oral environment and their biological and clinical implications. The available evidence differs substantially between the two materials. While titanium degradation is well documented and supported by both experimental and clinical studies, the evidence for a hybrid implant remains limited and is largely based on in vitro and mechanistic data. Full article

Colorectal cancer (CRC) shows consistent sex-related differences in incidence, anatomic distribution, molecular subtype, immune context, and clinical outcome. However, these differences are often discussed through broad parallel themes such as hormones, genetics, or the microbiome, rather than through the biological settings in which sex meaningfully modifies tumor behavior. This review argues that sex is most informative in CRC when treated as a contextual modifier whose relevance emerges only after integrating tumor sidedness, mismatch repair status, oncogenic background, immune ecology, and age at onset. The clearest signals arise from interaction-based contexts, particularly when sex is interpreted together with tumor sidedness and dMMR/MSI-H or BRAF-linked disease states. Current evidence indicates that women are enriched for proximal or right-sided, microsatellite instability-high, mismatch repair-deficient, CpG island methylator phenotype-high, and BRAF-associated CRC, whereas men more often present with distal disease and a higher overall burden. Mechanistic studies further show that sex-related differences extend beyond hormone exposure to include KRAS–STAT4–KDM5D signaling, site-specific immune-checkpoint programs, metabolic phenotypes, epigenetic biomarker variation, and microbiota–hormone crosstalk. These effects are most evident in defined clinical niches, particularly right-sided CRC, mismatch repair-deficient disease, BRAF-mutated metastatic CRC, and early-onset CRC. A sex-aware, subtype-aware, and location-aware framework therefore offers a more clinically useful interpretation of CRC heterogeneity than descriptive male-versus-female comparisons alone. Full article

Background: Intracavernosal platelet-rich plasma (PRP) is increasingly used for erectile dysfunction (ED), despite the absence of standardized biological characterization and clear dose definitions. This systematic review evaluates the clinical efficacy of PRP in ED while integrating emerging immune-centric mechanistic evidence. Methods: Following PRISMA 2020 guidelines, randomized controlled trials (RCTs) and prospective studies (2020–2025) investigating intracavernosal PRP in adult men with ED were identified across major databases. Validated outcomes included International Index of Erectile Function (IIEF-EF or IIEF-5), Erection Hardness Score (EHS), Sexual Encounter Profile (SEP), and penile Doppler parameters. Preclinical data were narratively integrated to contextualize biological plausibility. Results: Fourteen clinical studies met the inclusion criteria (six RCTs, eight prospective cohorts). Across most studies, PRP produced clinically relevant within-patient improvements, and three RCTs demonstrated minimal clinically important difference (MCID) responder rates compared with placebo. However, other trials showed comparable improvements in placebo arms, underscoring substantial contextual effects. Safety was consistently favourable. Marked heterogeneity in blood volume processed (10–120 mL), injected PRP volume (3–12 mL), preparation systems, and session protocols precluded cross-study comparability. Critically, no study reported platelet dose, leukocyte subsets, peripheral blood mononuclear cell (PBMNC) content, or red blood cell contamination. Preclinical models consistently demonstrate that PRP restores erectile function through angiogenic, neuroprotective, and immunomodulatory mechanisms, including CXCL5-mediated monocyte recruitment and M1-to-M2 macrophage polarization. Conclusions: Intracavernosal PRP shows promising short-term efficacy signals and a favourable short-term safety profile in mild-to-moderate vasculogenic ED, but current evidence is limited by profound biological and methodological heterogeneity. PRP should be reconsidered as an immune-regenerative intervention requiring dose-defined, composition-defined, and mechanistically informed randomized trials. Interpretation of these findings is constrained by the absence of formal risk-of-bias assessment for non-randomized studies, substantial clinical and biological heterogeneity across trials, and the lack of standardized PRP characterization. Full article

Low-molecular-weight gelators (LMWGs) have attracted growing attention as versatile alternatives to conventional polymeric thickeners and gelators, owing to their ability to form three-dimensional fibrillar networks through non-covalent self-assembly and to undergo reversible sol–gel transitions in response to external stimuli. Among the various stimuli that can be exploited, pH represents a particularly attractive trigger given its direct relevance to biological and physiological environments. This review focuses on three categories of pH-responsive LMWGs that have shown notable progress over the past decade yet remain relatively underexplored in the literature. First, N-oxide-type hydrogelators are discussed, with emphasis on amide amine oxide-based surfactants and pyridine-N-oxide frameworks. The pH-dependent protonation of the N-oxide moiety modulates intermolecular hydrogen bonding, thereby governing self-assembly and gel formation. The structural versatility of these gelators enables rational tuning of aggregate morphology and confers clear pH and temperature responsiveness. Second, recent advances in phenylboronic acid-based LMWGs are highlighted. Although boronic acid derivatives have long been studied as dynamic crosslinking units in polymeric hydrogels, 3-isobutoxyphenylboronic acid was recently identified as the first example of phenylboronic acid functioning as an LMWG, in which gelation is driven primarily by hydrogen bonding and pH responsiveness is exploited for stimuli-triggered gel disruption rather than gel formation. Third, pH-responsive orthogonal self-assembly systems are reviewed. Representative examples include multicomponent hybrid hydrogels combining pH-activated LMWGs with polymer gelators for controlled drug release, pH-triggered self-sorting of two LMWGs without any polymeric component, and bio-based orthogonal hydrogels composed of a glucolipid LMWG and cellulose nanocrystals. For each system, both advantages and remaining limitations are critically assessed. Collectively, this review aims to provide a timely overview of emerging trends in pH-responsive LMWG research and to offer perspectives on the rational design of next-generation stimuli-responsive soft materials. Full article

Plants of the genus Salacia (Celastraceae) have long been used in traditional medical systems of South and Southeast Asia for the management of diabetes and related metabolic disorders. Modern phytochemical and pharmacological studies have confirmed the antidiabetic potential of several Salacia species, leading to the identification of a distinctive group of sulfur-containing sugars as their principal bioactive constituents. Salacinol, neosalacinol, kotalanol, neokotalanol, and related analogues represent a novel class of thiosugar sulfonium compounds that act as potent and selective α-glucosidase inhibitors, providing a clear mechanistic basis for their glucose-lowering effects. Simpler thiosugars, such as 5-thiomannose, further contribute to the overall metabolic activity of Salacia extracts and may serve as biosynthetic or functional precursors. Beyond Salacia, sulfur-containing natural products are widespread in nature and perform diverse biological roles. In particular, the genus Allium is well known for producing organosulfur compounds, including thioethers and polysulfides, which exhibit antidiabetic, hypolipidemic, antioxidant, and cardioprotective activities. In a different context, sulfur-containing hopanes have been identified in sediments and petroleum as products of early diagenetic sulfurization of bacterial hopanoids. Although these compounds have been studied primarily as geochemical biomarkers, recent QSAR/PASS analyses suggest that sulfur hopanes may also possess biologically relevant activities, particularly related to metabolic and cardiovascular regulation. Recent PASS-based QSAR evaluations of Salacia-derived thiosugars and sulfur hopanes predict significant antidiabetic activity, including potential type 2 diabetes-related pharmacological effects, supported by predicted α-glucosidase inhibitory, hypoglycemic, hepatic, and gastrointestinal activities. Collectively, these findings highlight sulfur-containing natural products from both plant and sedimentary sources as chemically diverse yet functionally convergent scaffolds with promising potential for the development of functional foods and therapeutic agents targeting metabolic disorders. Full article

In the contemporary era, nanotechnology has become a central pillar in numerous domains, particularly in cosmetics, nanoelectronics, nanomedicine, and nanobiotechnology. Defined by its focus on materials with dimensions ranging from 0.1 to 100 nm, nanotechnology offers unique physicochemical properties—such as enhanced reactivity, conductivity, and permeability—attributable to the nanoscale. These properties facilitate greater interaction with biological systems, notably improving cellular uptake and functional efficacy. The increasing demand for eco-friendly and biocompatible nanomaterials has driven interest in green synthesis routes, particularly those utilising plant extracts. These methods stand out due to their low toxicity and environmental impact, positioning it as a safer alternative to conventional chemical or microbial methods. Plant-extract-mediated nanoparticles demonstrate promising applications in diagnostics, drug delivery, regenerative medicine, and neurotherapeutics. Their role in precision medicine, including gene and drug delivery and the imaging of neurological disorders, underscores green nanotechnology’s transformative potential. This review highlights recent advances in the synthesis, functionality, and biomedical applications of plant-based nanoparticles, emphasizing their relevance in in vitro models and prospective clinical settings. Full article

Background/Objectives: MSS-CRC comprises a heterogeneous group of tumors generally considered “immune cold” due to limited neoantigen generation and T-cell exclusion or inactivation. Current evidence indicates that the composition of T and B immune cells within the tumor microenvironment represents a prognostically relevant factor, significantly associated with both tumor expression profiles and molecular subtypes. Methods: We conducted an exploratory analysis to identify prognostically relevant immune cell components in this group of tumors and to investigate corresponding differences in RNA-based bulk expression and high-resolution spatial transcriptomic profiles. Results: A total of 254 localized mismatch repair-proficient colorectal cancer cases were evaluated. Our findings revealed PD-L1 expression as a robust independent prognostic biomarker associated with favorable outcomes in this specific population. Bulk RNA expression analysis showed that PD-L1-negative tumors exhibited an expression profile consistent with abundant cancer-associated fibroblast infiltration, increased matrix stiffness, and impaired immune activation—features consistent with tumor progression and poorer clinical outcomes. In contrast, PD-L1-positive tumors displayed stromal programs enriched in immune activation and controlled remodeling, consistent with an immunologically active microenvironment. Spatial transcriptomics added an additional layer of evidence, revealing that epithelial to mesenchymal transition-related programs can dominate stromal niches in PD-L1-negative tumors, particularly within macrophage-enriched stromal regions. Conclusions: Our observations suggest an association between PD-L1 expression on immune cells and immune-activated versus mesenchymal-dominant states, potentially occurring within macrophage-enriched stromal niches. These results provide insight into the biological mechanisms underlying disease progression and highlight tumor-associated macrophages as a potential therapeutic target to overcome immune resistance, particularly in PD-L1-negative MSS-CRC tumors. Full article