Search Results (922)

Background/Objectives: Spinal cord stimulation (SCS) is usually evaluated through pain relief, yet the published language of therapeutic success is broader. This structured narrative review examined success language in the SCS literature to map how outcome terminology has accumulated across domains. Methods: A PubMed/MEDLINE corpus was retrieved on 23 May 2026 using the strategy (“Spinal Cord Stimulation”[Mesh] OR “Spinal Cord Stimulation”[Title/Abstract]). The search returned 5719 records from 1961 to 2026. Title-and-abstract screening was performed independently by two authors, with pre-consensus agreement of 99.77% (Cohen’s κ = 0.995). After screening, 3687 records were retained for thematic narrative synthesis. Results: Pain relief or analgesic response appeared in 3550 retained records (96.3%) and remained the dominant outcome language across decades. Additional domains accumulated around it: function, quality of life, and sleep (72.5%); durability (55.5%); complications and device burden (51.0%); trial stimulation (44.1%); patient selection (40.5%); paresthesia coverage (29.9%); patient preference (24.5%); economic or occupational outcomes (22.8%); stimulation paradigm (21.9%); and medication use (21.3%). Physiological-feedback language was separated into mechanism-related language, objective monitoring, and evoked compound action potential (ECAP)-controlled closed-loop feedback. Conclusions: Within this corpus, SCS success emerged as a layered concept: analgesia remained central but was increasingly reported alongside other outcome domains rather than standing as the sole reported marker of therapeutic success. Importantly, this review maps the published language of outcome reporting, not clinical practice, payer behaviour, or any formal redefinition of treatment success; the findings should not be read as evidence that SCS success is now uniformly defined in multidimensional terms, and this scope is essential when interpreting the findings. Full article

One of the most pressing challenges facing healthcare today is the rise of biofilm infections and antibiotic-resistant bacteria, which demand entirely new therapeutic strategies beyond conventional antibiotic reliance. A biofilm is a structured community of microorganisms encased in a self-produced extracellular polymeric substance (EPS) matrix, which confers resistance to host immune defenses and antimicrobial agents. Accumulating evidence demonstrates that plant-derived secondary metabolites—including flavonoids, phenolic acids, tannins, terpenoids, and alkaloids—exert potent antibacterial and antibiofilm activities through diverse mechanisms of action. These natural compounds inhibit biofilm formation by disrupting bacterial adhesion, suppressing quorum sensing, degrading the EPS matrix, and impairing bacterial motility. Beyond independent bioactivity, phytochemicals demonstrate significant synergistic potential when combined with conventional antibiotics, revitalizing antimicrobial efficacy against drug-resistant pathogens. Nanoformulation and biogenic carrier technologies further enhance the bioavailability and therapeutic potency of these compounds. Despite these advances, critical challenges persist, including poor bioavailability, physicochemical instability, dose-dependent toxicity, and the risk of resistance development. This review presents a critical and integrative analysis of the pharmacological mechanisms of plant secondary metabolites, with particular emphasis on their role in combating biofilm-associated infections and antibiotic resistance, and discusses translational opportunities including structure–activity relationship (SAR)-guided optimization, high-throughput screening platforms, and advanced drug delivery systems. Collectively, plant secondary metabolites represent a scientifically compelling and clinically relevant pipeline for the development of next-generation antimicrobial and antibiofilm therapeutics. Full article

Nanotechnology has emerged as a promising strategy in restorative dentistry and endodontics due to the physicochemical and biological properties of nanomaterials. This narrative review aimed to critically analyze the current applications of nanomaterials in restorative dentistry and endodontics, highlighting their mechanisms of action, biological properties, and translational potential. A literature search was performed in the PubMed/MEDLINE database using combinations of MeSH terms and free keywords related to nanomaterials and dental applications. Studies published in English within the last twenty years and addressing restorative or endodontic applications were considered. After screening and eligibility assessment, 69 studies were included in the descriptive analysis. The findings indicate that nanomaterials have been investigated in preventive strategies, adhesive systems, restorative materials, intracanal medicaments, endodontic sealers, vital pulp therapy, and regenerative formulations. In restorative dentistry, nanoparticles such as silver nanoparticles, nano-hydroxyapatite, amorphous calcium phosphate, bioactive glass nanoparticles, and chitosan-based systems showed favorable antimicrobial, remineralizing, and material-enhancing properties. In endodontics, silver and chitosan nanoparticles showed potential for intracanal disinfection and biofilm disruption, while chlorhexidine, zinc, and bioactive glass nanoparticles enhanced the antimicrobial activity and sealing ability of endodontic sealers. In addition, magnetic nanoparticles, mesoporous silica nanoparticles, and hydroxyapatite nanoparticles presented promising applications in regenerative endodontics and vital pulp therapy. However, most of the available evidence is still based on in vitro studies, with limited long-term clinical validation. Overall, nanotechnology offers potential experimental advantages for improving preventive, restorative, and endodontic therapies; however, its successful clinical translation remains strictly dependent on overcoming critical biosafety barriers and addressing long-term toxicity concerns. Full article

Background: Visio-spatial skills (VSS) are fundamental perceptual–cognitive capacities that enable athletes to process dynamic visual information, interpret spatial relationships, and execute precise motor responses under competitive conditions. In taekwondo, where scoring actions are executed within milliseconds and success depends on the rapid detection and anticipation of an opponent’s movements, well-developed VSS are considered a functional prerequisite for performance. Method: This cross-sectional observational study examined differences in VSS between amateur taekwondo athletes (n = 50) and non-athletes (n = 50) recruited from the King Cetshwayo Municipality District, KwaZulu-Natal, South Africa. Six VSS were assessed using standardized, validated instruments: accommodation facility (AF), saccadic eye movement (SEM), speed of recognition (SR), hand–eye coordination (HEC), peripheral awareness (PA), and visual memory (VM). Between-group comparisons were performed using the Mann–Whitney U test, with effect sizes reported as rank-biserial correlations (r). Results: Taekwondo athletes demonstrated significantly superior performance across all VSS domains (all p ≤ 0.05), with a large effect observed for SR (r = 0.91), HEC (r = 0,87), SEM (r = 0.78), and AF (r = 0.74), and moderate effect for VM (r = 0.58) and PA (r = 031). The largest between-group percentage differences were observed for SR (79.43%), HEC (48.13%), and SEM (33.33%), with smaller but significant differences in AF (31.05%), VM (14.92%), and PA (4.23%). Pearson correlation analysis revealed a dense, globally integrated VSS network in non-athletes anchored by AF, contrasting with a sparse pattern in taekwondo athletes, in which SEM showed the greatest number of moderate or stronger associations with other variables. These within-group correlation structures are presented as preliminary and descriptive observations only. Intraclass correlation coefficients were excellent for five of the six VSS (ICC ≥ 0.963), with PA yielding a point estimate of ICC = 0.853, characterized by a wide confidence interval. Conclusions: These findings indicate that amateur taekwondo athletes show superior perceptual, oculomotor, and visuo-motor performance compared to non-athletes. Within-group VSS correlation pattern differs descriptively between the groups. The cross-sectional design cannot determine whether these differences reflect training-associated perceptual adaptation, pre-existing trait-based self-selection into taekwondo, or a combination of both mechanisms. Both interpretations carry applied implications for talent identification and vision training program design. A longitudinal investigation is required to establish causal directionality. SEM and AF are proposed as the most diagnostically informative VSS markers for taekwondo screening, under either interpretation. Full article

Background: Autoimmune diseases such as primary Sjögren’s syndrome and type 1 diabetes are frequently complicated by hepatic injury, yet therapies that simultaneously target inflammation and parenchymal damage remain limited. Mitochondrial dysfunction with excessive reactive oxygen species (ROS) production drives a self-amplifying pathogenic loop by activating the cGAS-STING innate immune pathway. We previously observed that a Chinese herbal formula preserved mitochondrial ultrastructure in autoimmune NOD mice, and computational screening identified trifolirhizin—a natural pterocarpan flavonoid—as the candidate active constituent mediating this protection. Here, we investigated the hepatoprotective effects and underlying mechanisms of trifolirhizin in autoimmune-associated liver injury. Methods: Female NOD mice received trifolirhizin (5, 10, or 20 mg/kg/day) for four weeks, with C57BL/6J mice as healthy controls. Hepatic histopathology, inflammatory cytokines, mitochondrial ultrastructure (TEM), mitochondrial membrane potential (ΔΨm), and ROS levels were evaluated. Integrated transcriptomic and metabolomic profiling was performed to unbiasedly characterize protective mechanisms. In vitro, H₂O₂-induced oxidative stress was established in HepG2 cells. Cells were treated with trifolirhizin (15–25 µM) and assessed for antioxidant enzyme activities, ΔΨm, ROS production, glycolytic and mitochondrial respiration (Seahorse analysis), and cGAS-STING pathway protein expression. Pharmacological rescue experiments using the cGAS agonist cGAMP were conducted to test pathway dependency. Results: Trifolirhizin dose-dependently alleviated hepatic pathological damage and reduced pro-inflammatory cytokine levels in NOD mice. Multi-omics profiling revealed that oxidative stress responses, the mitochondrial electron transport chain, and glutathione metabolism were the most significantly restored pathways. Trifolirhizin preserved mitochondrial ultrastructure, restored ΔΨm, and attenuated ROS accumulation both in vivo and in vitro. Functionally, Seahorse analysis demonstrated that trifolirhizin rescued overall cellular bioenergetics, restoring both glycolytic capacity and mitochondrial respiratory parameters (basal respiration, ATP production, maximal respiration, and spare respiratory capacity). Mechanistically, trifolirhizin suppressed the cGAS-STING-TBK1-IRF3 axis, as evidenced by reduced expression of cGAS, p-STING, ZBP1, p-TBK1, and p-IRF3. Importantly, the cGAS agonist cGAMP abrogated the protective effects of trifolirhizin, confirming that the cGAS-STING pathway is functionally required for its action downstream of mitochondrial protection. Conclusion: Trifolirhizin attenuates liver injury in the nod mouse by preserving mitochondrial integrity, maintaining cellular energy metabolism, and thereby suppressing the ROS/cGAS-STING inflammatory cascade. These findings position trifolirhizin as a promising mitochondria-targeted therapeutic candidate for pSS-related hepatic complications and provide a mechanistic framework for discovering active compounds from mitochondrially active herbal formulations. Full article

Antimicrobial resistance is increasing, necessitating the development of novel and efficacious therapies. Plants contain phytochemicals, some of which may possess antibacterial properties. This research employed broth dilution experiments to investigate the antibacterial efficacy of fifteen phytochemicals identified in medicinal plant extracts. The sum of fractional inhibitory concentration of phytochemicals in conjunction with reference antibiotics were also analysed. The inhibitory effects of phytochemicals against β-lactamase were evaluated to explore their potential mechanisms of action. The phytochemicals were evaluated for toxicity on human dermal fibroblast cells. Gallic acid and luteolin significantly inhibited Staphylococcus aureus and the methicillin-resistant S. aureus (MRSA) strain, with minimum inhibitory concentration (MICs) of 62.5 µg/mL. Gallic acid also demonstrated restricted efficacy against Gram-negative species, with MICs ranging from 312.5 to 1250 µg/mL. Gram-negative bacteria exhibited no response to luteolin. Ellagic acid, catechin, naringenin, and quercetin exhibited moderate antibacterial efficacy against the tested pathogens (625–2500 µg/mL MIC). Corilagin exhibited significant antibacterial activity against S. aureus and MRSA, with a MIC of 7.81 µg/mL. Corilagin also exhibited notable efficacy against Bacillus cereus, Shigella flexneri, and Klebsiella pneumoniae, with MICs ranging from 62.5 to 250 µg/mL. Fractional inhibitory concentration studies revealed a synergistic effect between amoxicillin and corilagin against B. cereus. Additionally, catechin, luteolin, and quercetin synergised penicillin G against S. aureus. Quercetin potentiated the activity of β-lactams (amoxicillin, penicillin G, and oxacillin) against MRSA. Notably, these antibiotics were ineffective against MRSA alone. Isobologram analysis revealed potentiation between penicillin G and quercetin against MRSA at all tested ratios. The β-lactamase inhibitory activity of the phytochemicals was evaluated using a commercial screening kit, and the percentage of relative inhibition was determined. Quercetin and luteolin both inhibited β-lactamase, achieving relative inhibition rates of 77–100% across two time intervals. All phytochemicals were nontoxic against human dermal fibroblasts. Indeed, quercetin enhanced cell survival by 200%. Full article

Background/Objectives: Cancer is a multifactorial disease in which drug resistance and limited selectivity remain major therapeutic challenges, highlighting the need for novel anticancer agents. As a privileged scaffold for multitarget anticancer drug discovery, quinazolin-4(3H)-one was selected for the design, synthesis, and evaluation of new derivatives as potential anticancer agents, together with investigation of their mechanisms of action and molecular targets. Methods: Fifteen new quinazolin-4(3H)-one derivatives were synthesized and screened using the NCI-60 human cancer cell line panel. The mechanism of action of the most active compound was investigated through cell cycle, apoptosis, and RT-qPCR analyses. A potential molecular target was identified from transcriptomic data in the Human Protein Atlas, focusing on highly expressed cancer-implicated genes in the most responsive cell lines, followed by molecular docking, molecular dynamics simulations, and in vitro kinase studies. Safety and pharmacokinetic properties were evaluated using an MTT cytotoxicity assay in normal WI-38 fibroblasts and in silico ADME analyses. Results: Compound 3e emerged as the most active and tumor-selective derivative, exhibiting GI₅₀ values ranging from 2.63 to 17.12 µM across 31 cancer cell lines. In A549 cells, selected as a representative responsive model, 3e (GI₅₀ = 10.8 µM, 72 h) induced G2/M cell-cycle arrest (59.58% vs. 26.96% in control), increased early apoptosis (43.94% vs. 0.11% in control), reduced viable cells (49.71% vs. 98.66%), elevated the Bax/Bcl-2 ratio (7.91), and upregulated the expression of caspase-9 and caspase-3 by 2.5- and 4.6-fold, respectively. Integrated target identification studies and an in vitro kinase assay (IC₅₀ = 21.34 nM) suggested TGF-βRI (ALK5) as a plausible molecular target. Compound 3e also showed low cytotoxicity toward WI-38 fibroblasts (IC₅₀ = 88.3 µM) and favorable predicted pharmacokinetic properties; nevertheless, high plasma protein binding and potential CYP2C9 inhibition are anticipated. Conclusions: Compound 3e is a promising tumor-selective anticancer lead with potential TGF-βRI inhibitory activity. Its antiproliferative effects in A549 cells appear to be mediated through G2/M cell-cycle arrest and activation of the intrinsic apoptotic pathway, supporting further development and pharmacokinetic optimization of this scaffold for anticancer therapy. Full article

Endogenous gene tagging using CRISPR has changed the understanding of the role played by different proteins due to the ability to track and study proteins in their natural state. With CRISPR-based gene tagging, it is possible to insert fluorescent, luminescent, epitope, affinity, and proximity labels into the target protein at its endogenous genomic location without affecting its physiological expression and dynamics. Here, we discuss the DNA-repair mechanisms employed in endogenous gene tagging, including homology-dependent repair, NHEJ-based integration, and alternative approaches that can be used with challenging cell types. Key aspects of efficient CRISPR tagging experiments are also described. Additionally, we review recent advances in the increasing array of protein tag technologies, including fluorescent proteins, split-reporter technologies, NanoLuc/HiBiT, peptide epitopes, and proximity biotinylation enzymes. Lastly, we review the scalability of endogenous tagging approaches using multiplex editing, atlas-scale proteome tagging, iPSC-based disease modeling, and drug discovery platforms for assessing target engagement, protein degradation, phenotype screening, and mechanism of action of compounds. Although difficult in primary and pluripotent cells, new methods based on avoiding double-strand breaks, such as prime editing, PASTE, and CRISPR associated transposases, will drive the future expansion of endogenous tagging approaches. Such developments firmly set up CRISPR gene tagging as a fundamental technology in quantitative cell biology and translational pharmacology. Full article

Background: Type 2 diabetes mellitus (T2DM) is a global health challenge characterized by chronic hyperglycemia and oxidative stress. Pithecellobium dulce root has long been recognized for its antidiabetic potential; however, its specific bioactive constituents and mechanisms of action remain poorly defined. This study aimed to evaluate the antidiabetic and antioxidant properties of extracts and isolated molecules from P. dulce root bark. Methods: The DCM/MeOH crude extract of P. dulce root bark was fractionated with n-hexane (PDEH) and ethyl acetate (PDAE), followed by chromatographic purification and spectroscopic characterization, yielding seventeen compounds (1–17). The antioxidant activity (DPPH, ABTS, FRAP) and antidiabetic potential of PDEH, PDAE, and 1–17 were assessed in vitro using yeast-derived enzymes and in silico (targeting human α-glucosidase [PDB: 2QLY] and human α-amylase [PDB: 4GQR]). The in vitro α-glucosidase experiments used saccharomyces cerevisiae enzyme, which varies from the human target. Therefore, these results should be taken as preliminary screening data that needs confirmation with human enzymes. Results: Compound 1 was identified as new, while 2 was isolated for the first time from a natural source. The cell-free chemical tests DPPH, ABTS, and FRAP measured antioxidant capability. These tests quantify radical-scavenging and electron-transfer capabilities in vitro and are preliminary chemical screening methods. They do not directly represent biological antioxidant activity in cells or organisms. PDEH demonstrated strong radical scavenging against DPPH (IC₅₀ = 15.30 μg/mL) and ABTS (IC₅₀ = 12.80 μg/mL), while pristriol (16) showed ferric reducing power (EC₅₀ = 4200 μM FeSO₄/g). Enzyme inhibition assays demonstrated activity against α-amylase (IC₅₀ 53.88–112.24 µg/mL; acarbose IC₅₀ = 91.20 µg/mL) and α-glucosidase (IC₅₀ 18.38–136.88 µg/mL; acarbose IC₅₀ = 11.31 µg/mL). Compounds 15, 1, and 2 showed superior activity compared to acarbose for α-amylase, with effect sizes (Cohen’s d) of 2.15, 0.94, and 0.82, respectively, and IC₅₀ values of 53.88, 88.15, and 92.62 µg/mL; for α-glucosidase, IC₅₀ values were 18.38, 39.25, and 36.40 µg/mL, respectively. Docking studies supported these findings, revealing binding energies of −9.08, −8.34, and −7.22 kcal/mol for compounds 1, 2, and 15 with α-amylase, and −10.35 and −9.79 kcal/mol for compounds 1 and 2 with α-glucosidase. ADME profiling further identified 1 and 2 as promising lead candidates for dual-enzyme inhibition. Conclusions: P. dulce root bark represents a potent source of bioactive molecules with both antioxidant and dual-enzyme-inhibitory properties. These findings validate its traditional use and highlight its potential in the development of multitarget therapies for T2DM management. Full article

Untreated dental caries in permanent teeth is the most frequent disease of all 371 diseases and traumas assessed by the Global Burden of Disease Study in 2021, and there are reported to be 2.24 billion cases worldwide. Demineralization is a disintegration process of minerals and apatite crystals in hard tissue, provoked by biofilm activities, dietary factors, and the micro-oral environment—the three main mechanisms of dental caries. Restoration of mineral ions in the crystal structure is defined as remineralization. Remineralization enables the deposition of new minerals within the crystal structure of demineralized enamel, aiming to increase mineral production. Environments suitable for remineralization and inhibiting demineralization could be created by using a caries prevention agent. Objectives: Providing scientific evidence regarding Aloe vera as an alternative agent for caries prevention. Materials and Method: The method used in this study is a scoping review, utilizing the PRISMA-ScR as a guideline to conduct article screening and further analysis, following a thematic analysis approach. Database searches were conducted in PubMed, EBSCOhost, and ScienceDirect, based on the keywords generated. Results: A total of 13 articles were gathered for further analysis. Conclusions: Aloe vera shows promising preliminary potential, but further standardized in vivo and randomized clinical studies are necessary to confirm its remineralizing efficacy and clarify its mechanisms of action as a cavity prevention agent. Clinical Relevance: Using Aloe vera as an alternative caries prevention agent. Full article

Background/Objectives: Antimicrobial resistance in pediatric infections presents a worsening global public health challenge, with antimicrobial resistance (AMR) accounting for more than one million deaths annually and disproportionately affecting children younger than 5 years of age. Neonates and critically ill children face heightened risk owing to immature immunity, frequent healthcare exposures, and limited therapeutic options. This review synthesizes evidence on the epidemiology, mechanisms of resistance, clinical outcomes, and management of AMR across the full pediatric age range. Methods: PubMed/MEDLINE and Google Scholar were searched for literature from 2014 to 2026 using terms covering antibiotic resistance, pediatric populations, and key pathogens. Approximately 1840 records were screened; 69 sources met all inclusion criteria. A narrative synthesis approach was used, given heterogeneity across study designs and outcomes. Results: Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, carbapenem-resistant pathogens, and methicillin-resistant Staphylococcus aureus drive substantial morbidity and mortality in children. Approximately one in five pediatric Gram-negative bloodstream isolates are resistant to third-generation cephalosporins, a phenotype independently associated with a roughly three-fold increase in adjusted mortality. Carbapenem-resistant Klebsiella pneumoniae bacteremia carries a 30-day mortality approaching 40%, and isolates in low- and middle-income countries (LMICs) frequently harbor multiple resistance genes. Pneumococcal conjugate vaccine implementation was associated with absolute reductions of 7–11% in the proportion of pediatric pneumococcal isolates that were penicillin-non-susceptible or penicillin-resistant, largely by preventing infections caused by resistant serotypes and by reducing antibiotic selection pressure, rather than through a direct effect on resistance mechanisms; global AMR mortality in children younger than 5 years of age fell by more than 50% between 1990 and 2021. Conclusions: Pediatric AMR reflects intersecting microbiological, clinical, and health-system challenges. Priority actions include scaling antimicrobial stewardship programs, expanding access to rapid molecular diagnostics, integrating whole-genome sequencing into surveillance, conducting pediatric-inclusive randomized trials, and deploying vaccines as primary prevention tools, with particular emphasis on LMICs where the burden is greatest. Full article

As the global population continues to age, mental health issues such as depression, anxiety, stress, loneliness, and social isolation among older adults are receiving increasing attention. The built environment is closely associated with older adults’ daily mobility, environmental perception, social participation, and mental health and well-being, but the evidence remains heterogeneous across spatial contexts, environmental indicators, and study designs. Previous umbrella reviews have summarized broad links between the built environment and healthy aging, but less attention has been paid to recent original empirical studies published after the COVID-19 pandemic, the distinction between objective environmental exposure and subjective environmental perception, and the role of social participation as a pathway linking environmental conditions to mental health and well-being. This study employs a systematic literature review approach, searching and screening peer-reviewed empirical studies published between 2015 and January 2026 that focus on the associations between the built environment and older adults’ mental health and well-being. PubMed, Scopus, and Web of Science databases were used for searching, supplemented by manual searching. After title and abstract screening and full-text evaluation, a total of 60 studies were included. Subsequently, a comprehensive analysis was conducted on aspects such as research design, spatial scale, environmental indicators, types of mental health outcomes, and potential pathways of action. In this review, core mental health and well-being outcomes included negative outcomes, such as depression, anxiety, stress, psychological distress, loneliness, and social isolation, and positive outcomes, such as life satisfaction, subjective well-being, psychological well-being, and mental well-being. Social participation was examined as a behavioral and psychosocial pathway rather than as a core outcome. Emerging methods, including street-view image analysis, FCN-based semantic segmentation, and XGBoost-SHAP, were examined because they can refine environmental exposure measurement and support variable-importance interpretation, rather than because they provide causal evidence. The main synthesis suggests that several built environment factors are associated with older adults’ mental health and well-being, although the strength and consistency of evidence vary across outcome types, spatial contexts, and study designs. (1) Exposure to green and blue spaces, quality of public open spaces, walkability and accessibility, accessibility of neighborhood facilities and services, housing and living conditions, and positive environmental perception are mostly associated with lower levels of depression, anxiety, stress, and loneliness, as well as higher levels of life satisfaction, subjective well-being, and psychological well-being. (2) Conversely, adverse environmental exposures such as proximity to roads, pollution, non-vegetated spaces, and high-intensity urbanization are more likely to exacerbate negative psychological outcomes. Existing evidence also suggests that social participation is one of the important behavioral pathways through which the built environment is linked to the mental health of older adults, but it is not the only mechanism. (3) In addition, the direction and intensity of environmental associations remain heterogeneous under different spatial scales, indicator types, and research methods. Overall, this review contributes by organizing recent empirical evidence into a built environment–social participation–mental health and well-being framework, while emphasizing that most findings should be interpreted primarily as evidence of association rather than as stable or uniform causal effects. Full article

Hydrogel-based optical sensors have emerged as a versatile class of analytical materials that combine soft-matter processability, tunable network chemistry, and compatibility with luminescent, colorimetric, photonic, and hybrid transduction strategies. Progress in the field is driven not by a single sensing mechanism, but by the convergence of key advances in material functionalization, embedded selectivity, operation across diverse sample matrices, mechanical and analytical robustness, and usability beyond the laboratory. Current systems include framework-integrated, nanoparticle-doped, probe-functionalized, photonic-crystal, enzyme-immobilized, and device-coupled hydrogels, reflecting growing architectural diversity and application-oriented engineering. Selectivity has likewise advanced from basic interferent screening to recognition-specific, imprinted, and pattern-discriminative formats suited to complex environmental, food, biological, and wearable settings. Evidence of stability, reusability, and deformation tolerance further suggests that many platforms are moving beyond proof-of-concept demonstrations toward credible real-world operation. At the same time, translational priorities such as portability, smartphone readout, implantable and epidermal formats, and multifunctionality spanning antimicrobial action, adsorption, anti-counterfeiting, and device integration are becoming increasingly prominent. Together, these trends show that hydrogel-based optical sensing is maturing into a materially rich, application-responsive domain. The key challenge ahead is to unify materials design, selectivity control, durability, and deployability in standardized, reproducible, and clinically or environmentally credible sensing platforms. Full article

Background/Objectives: Heliotropium indicum (H. indicum) is a medicinal plant traditionally used for conditions associated with inflammation, but its active antinociceptive constituents remain poorly defined. This study evaluated the antinociceptive activity of the aerial parts of H. indicum through a bioassay-guided approach and explored the mechanism of action of the active compound isolated in the formalin test. Methods: Three extracts of H. indicum (hexane, dichloromethane, and methanol) were evaluated in male Swiss albino CD-1 mice using the formalin test. The most active extract was fractionated, and its major fractions were screened for antinociceptive activity. Based on the active fraction and previous phytochemical data, (E)-ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate (ECDE) was selected for further pharmacological evaluation in the same model. Antagonist pretreatments were used to investigate the involvement of opioid, serotonergic, gamma-aminobutyric acid (GABA_A), and Nitric Oxide (NO)–soluble Guanylyl Cyclase (sGC) pathways. Results: The three extracts reduced nociceptive behavior, mainly during phase II of the formalin test, whereas the dichloromethane extract showed the broadest activity profile and was selected for fractionation. The six fractions significantly reduced phase II nociception, and fraction F5 was selected for purification. ECDE produced a clear dose-dependent antinociceptive effect in phase II, with minimal effect on phase I, and its efficacy was compared with that of ketorolac, a standard antinociceptive drug. Dose–response analysis estimated a DE₅₀ of 0.76 mg/kg for ECDE. Pretreatment with N-nitro-L-arginine methyl ester (L-NAME) and [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) significantly attenuated the effect of ECDE, whereas naloxone, methiothepin, and bicuculline did not. Conclusions: ECDE was identified in H. indicum as one of the compounds contributing to this effect. Its activity appears to be directed mainly toward inflammatory nociception and to depend, at least in part, on the NO–sGC pathway. Full article

Background/Objectives: Natural products have long been regarded as a cornerstone in the discovery and development of novel therapeutic agents. Accumulating evidence indicates that natural products represent promising pharmacological candidates for cancer treatment. This review provides a holistic overview of novel identified natural products as a continuing source of bioactive compounds, with particular emphasis on recent advances and their applications in anticancer therapy over the past five years. Methods: A literature search was conducted using PubMed, Scopus, and Web of Science to identify relevant studies published within the past five years. Predefined keywords and Boolean operators (e.g., “natural products”, “anticancer”, “drug discovery”, “secondary metabolites”, “signaling pathways”, “epigenetics”) were applied, with search strategies adapted to each database. Eligible studies included original research articles and reviews reporting on newly identified natural products with anticancer activity, with emphasis on chemical diversity, biological effects, and molecular mechanisms of action. Additional references were identified through manual screening of bibliographies. The selected literature was evaluated using a qualitative, interpretative approach consistent with narrative review methodology, and findings were critically synthesized and thematically organized. Results: Growing evidence indicates that multiple newly identified natural products target mitochondrial metabolism and interact with alternative tubulin binding sites, thereby highlighting their potential as anticancer agents. In addition, emerging compounds have been shown to affect DNA integrity and transcriptional regulation, while also acting as systems-level modulators of key oncogenic signaling pathways, including PI3K/Akt, NF-κB, and MAPK. Recent studies further demonstrate that natural products can modulate multiple layers of epigenetic regulation, including DNA methylation, histone acetylation, histone methylation, and non-coding RNA networks. Conclusions: Current evidence supports the concept that natural products primarily function as multi-target biological modulators rather than classical single-target inhibitors in cancer biology. A persistent challenge remains the translational gap between preclinical efficacy and clinical application, as the majority of naturally derived candidate compounds remain confined to in vitro or early in vivo validation. Future progress will therefore depend on systematically aligning the multi-target pharmacology of natural products with defined cancer vulnerabilities and clinically actionable therapeutic strategies. Full article