The use of cytostatic drugs for cancer treatment is currently the main weapon in the fight against cancer; however, prolonged exposure of healthcare personnel can cause adverse toxic effects. Objective: To determine the genotoxicity caused by exposure to cytostatic drugs, using the comet assay, in workers in the oncology department of a tertiary hospital in northern Peru. Methodology: Descriptive, quantitative, correlational, and cross-sectional study. The population consisted of two groups of workers: exposed (n = 40) and unexposed (n = 40). The alkaline lysis comet DNA technique was used on peripheral blood cells; tailing moment and tailing percentage indicators were evaluated. Results: Using nonparametric tests, the percentage and tail moment showed no significant differences, with p values of 0.8928 and 0.4675, respectively. The distribution observed in the group exposed to cytostatic drugs (pharmacists and pharmacy technicians) compared to the control group showed a normal distribution, with a tail moment of 8.29 vs. 3.03 and a percentage of tail of 37.12 vs. 23.24, respectively. Multivariate analysis showed that the tail moment variable was 11.56% greater in the group of pharmacists and pharmacy technicians (p = 0.0119) compared to the other participants. Conclusions: Although no significant difference was found, a trend toward a higher percentage and tail moment was observed in the group exposed to cytostatic drugs. Furthermore, the group of pharmacists and pharmacy technicians, compared to the other professions, showed significantly greater damage.
Background: Aralia echinocaulis has therapeutic effects on rheumatoid arthritis (RA), with total polysaccharide and glycoside (TPGs) as main active components. RA pathogenesis involves gut microbiota dysbiosis and immune-metabolic crosstalk, but the role of microbiota-derived succinate in RA remains unclear. Objective: This study explored the role of succinate-GPR91 signaling in intestinal dendritic cells (DCs) in the context of RA and the therapeutic mechanism of A. echinocaulis TPGs. Methods: Collagen-induced arthritis (CIA) mice were treated with TPGs or exogenous succinate. Paw edema, inflammation, gut succinate levels, the Th17/regulatory T (Treg) balance, and DC activation via succinate-GPR91 were detected, and GPR91-targeting siRNA and CD4+ T-cell coculture assays for verification. Results: TPGs alleviated symptoms in CIA mice and restored the Th17/Treg balance by reducing intestinal succinate levels. Succinate activated DCs via GPR91 to promote Th17 differentiation, while TPGs suppressed DC maturation and Th17-driven inflammation, supporting the involvement of a gut-centric immunometabolic axis in RA. Conclusions: TPGs ameliorate RA by targeting the succinate-GPR91-Th17 pathway, identifying succinate as a novel RA target and TPGs as a potential microbiota-modulating agent.
Background: Psidium guajava L. (Psidium guajava) is an edible plant; its parts are widely used to cure and prevent many health disorders. Psidium guajava leaves contain a wide array of polyphenols that inhibit peroxidation and may play a role in the prevention and treatment of common, degenerative chronic disorders such as diabetes, cardiovascular disease, and cancer. Colon cancer is the third most common type of cancer diagnosed and the second most common cause of cancer-related deaths globally. In contrast, prostate cancer is the second most diagnosed cancer and the fifth leading cause of cancer-related death worldwide. This study aims to evaluate the pharmacological potential of the Psidium guajava plants cultivated in Romania on colon and prostate cancer cell lines. Methods: Phenolic compounds extraction was made using an average sample of all nine Psidium guajava varieties. Analyses were carried out using a HP-1200 liquid chromatograph. The effect of the alcoholic extract of Psidium guajava leaves was tested on two colon cancer and one prostate cancer cell line as in vitro models. Results: The Psidium guajava leaf extract exhibited anticancer activity against the tested cell lines, with decreased proliferation, increased apoptosis, and cell cycle arrest. The extract reduced the cancer cell line's migration and invasion capacity, demonstrating greater selectivity for the colon cancer cell line than for the prostate cancer cell lines. Conclusions: This study provides further proof of the Psidium guajava plant's anticancer properties against colon cancer cell lines. Further studies are needed to confirm its use either alone or in conjunction with conventional cancer treatments as an alternate treatment for certain kinds of malignancies.
Background: Wound healing remains a major clinical challenge, often impaired by persistent inflammation, oxidative stress, and abnormal extracellular matrix remodeling. Electrospun nanofibers (NFs) have emerged as promising wound dressing platforms due to their biomimetic structure and capacity to incorporate multiple bioactive compounds (ACs) with synergistic therapeutic effects. Objectives: This study aimed to biologically assess novel chitosan/poly(vinyl alcohol) (CH/PVA) NFs functionalized with natural active compounds (L-arginine-ARG, allantoin-ALA, royal jelly-RJ, and curcumin-CUR) as multifunctional systems for wound healing and tissue remodeling. Methods: The nanofibrous systems performed the in vitro evaluation of antioxidant activity (DPPH, ABTS, FRAP, PRAP), anti-inflammatory potential (protein denaturation test), hemocompatibility, and cytocompatibility using dermal fibroblasts. In vivo healing performance was evaluated in an excisional wound model using macroscopic wound contraction analysis, histopathology, and immunohistochemical staining (MMP-9, CD31, VEGF-A, α-SMA). Results: The bioactive-enriched CH/PVA NFs exhibited strong antioxidant and anti-inflammatory activity, excellent hemocompatibility (hemolysis < 5%), and excellent cytocompatibility, with promoting fibroblast proliferation. In vivo experiments revealed that the treated groups exhibited accelerated wound closure, improved re-epithelialization, increased angiogenesis, and showed more efficient tissue remodeling compared to the controls, as validated by histological and immunohistochemical studies. Conclusions: The findings indicate that bioactive-enriched CH/PVA NFs serve as effective, biocompatible, and multifunctional matrices for wound healing, hence endorsing their potential for further translational advancement in skin regeneration applications.
Background/Objectives: Salidroside, a bioactive phenylethanol glycoside primarily derived from Rhodiola rosea, and its major in vivo metabolite tyrosol exhibit diverse pharmacological activities. However, their direct molecular targets remain poorly defined. Methods: In the present study, an integrated strategy combining transcriptomic profiling, Connectivity Map (CMap) analysis, and multi-level experimental validation was employed. Transcriptomic signatures derived from A549 cells treated with salidroside or tyrosol were queried against the CMap database. Molecular docking, surface plasmon resonance (SPR), and cellular thermal shift assays (CETSA) were performed to predict and validate binding interactions. Functional validation was performed in SH-SY5Y cells. The phosphorylation level of extracellular signal-regulated kinase (ERK), a downstream signaling event of dopamine D2 receptor (DRD2), was detected after salidroside and tyrosol treatment. DRD2 antagonist sulpiride pre-intervention and small interfering RNA (siRNA)-mediated DRD2 knockdown were conducted to verify the receptor dependence of the compounds' effects. Results: CMap analysis revealed that the transcriptomic signatures of salidroside and tyrosol showed significant similarity to known DRD2 modulators. Molecular docking predicted potential binding interactions between the two compounds and DRD2, which was confirmed by SPR and CETSA to be direct physical binding. Functional studies showed that both compounds rapidly induced DRD2 downstream ERK phosphorylation in SH-SY5Y cells; this effect was abrogated by sulpiride or DRD2 knockdown, indicating DRD2-dependent signaling activation. Conclusions: These findings identify DRD2 as a direct molecular target of salidroside and tyrosol and provide mechanistic insight into their dopaminergic regulatory effects. This study highlights the utility of CMap-guided target discovery combined with rigorous experimental validation for elucidating the molecular mechanisms of natural products.
Background/Objectives: Amorphous solid dispersions (ASDs) produced via hot-melt extrusion (HME) and fused deposition modeling (FDM) 3D printing represent a promising strategy for improving the performance of poorly water-soluble drugs. However, the integrated HME-FDM workflow is inherently energy-intensive, and sustainability considerations are rarely incorporated into formulation and process optimization. The present study aimed to develop and optimize indomethacin (IND) ASDs using a systematic Design of Experiment (DoE) framework that integrates electrical energy consumption as a quantitative response alongside pharmaceutical performance attributes. Methods: Polymer-plasticizer miscibility was screened using hot-stage microscopy, followed by filament preparation via HME. A factorial DoE was applied to optimize drug loading and extrusion temperature considering electrical energy consumption, extrusion yield, encapsulation efficiency, and residual crystallinity. Solid-state characterization was performed using DSC and XRD. The optimized filament was subsequently subjected to geometry screening and a second DoE to optimize platform temperature, nozzle temperature, and printing speed with respect to printing time, electrical energy consumption, and drug assay. Results: Complete drug amorphization was achieved within a defined thermal window, with residual crystallinity governed by kinetic dissolution constraints at lower extrusion temperatures. Electrical energy demand during both HME and FDM was strongly influenced by thermal setpoints and process duration. Multi-response overlay analysis identified sustainability-oriented operating windows for both stages. Experimental validation confirmed close agreement between predicted and observed responses, demonstrating simultaneous reduction in electrical demand and maintenance of dose accuracy and solid-state stability. Conclusions: This study demonstrates that electrical energy consumption can be systematically embedded as a quantitative design variable in pharmaceutical process optimization. The proposed dual-stage DoE strategy establishes a rational framework for developing 3D-printed ASD dosage forms that balance molecular performance and environmental efficiency.
Emotional aspects of early dental experiences have long-lasting effects. This study aimed to assess parents' childhood dental experiences and their impact on current attitudes toward dental treatment and to evaluate the subjectively perceived usefulness of an educational material focused on psychological management of children's dental visits. A cross-sectional descriptive pilot study was conducted using an educational booklet developed and distributed to parents, who read it and completed a short questionnaire. Responses received between 27 February-31 March 2025 were analyzed using IBM SPSS Statistics 25. A total of 142 parents (88% mothers) participated. Most participants (83.1%) had a university degree. Negative childhood dental experiences were reported by 44.4% (more frequent among mothers, p < 0.001), and 18.3% had shared these experiences with their children. Emotional discomfort during dental visits was reported by 61.3% of respondents. Dental anxiety was significantly associated with negative childhood experiences (p < 0.001). Parents with higher education were more likely to choose a certified paedodontist for their child than a nearby general dentist (p = 0.002). Most parents (97.9%) found the material provided helpful for managing future dental visits, and 91.6% were willing to share it with others. Childhood dental fear and anxiety may persist into adulthood. Despite the limited generalizability of our results, parents appreciated targeted resources which may support them in promoting positive dental experiences for their children.
Multidrug resistance (MDR) and chemotherapy-associated toxicity remain major challenges limiting the success of cancer treatments. In this context, berberine (BBR), an isoquinoline derivative belonging to the barberry family, has emerged as a promising adjuvant that can enhance the efficacy of chemotherapy while potentially mitigating its side effects. The findings indicate that berberine enhances the therapeutic effect of several drugs, such as doxorubicin, cisplatin, tamoxifen, and 5-fluorouracil, through multiple mechanisms including the inhibition of ABC transporters, regulation of autophagy, and synergistic enhancement of reactive oxygen species generation. Advanced pharmaceutical and nanotechnological formulations, including cyclodextrin complexes, solid dispersions, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, chitosan-based systems, and inorganic nanoplatforms, have demonstrated significant improvements in the solubility, stability, cellular uptake, and oral bioavailability of berberine. However, knowledge gaps remain regarding optimal dosage determination, safety assessment in combination therapy, and establishing efficacy in large-scale clinical trials. Incorporating berberine into combination therapy strategies may improve treatment outcomes, overcome drug resistance, and potentially reduce the toxic burden associated with chemotherapy. Therefore, this review provides a comprehensive analytical framework for berberine's potential as an adjuvant, elucidates its mechanistic synergistic interactions with standard therapies, explores pharmaceutical strategies to overcome bioavailability limitations, and suggests future research avenues to further its clinical development.
Background: Cephalosporins, widely used β-lactam antibiotics, are becoming significant environmental pollutants, primarily due to their high use and persistence. They are released into the environment mainly through wastewater treatment plants, agricultural runoff, and hospital discharge, with particularly high concentrations recorded in effluents. Conventional wastewater treatment methods have inadequate removal efficiency, while advanced treatments, such as ozonation, activated carbon adsorption, and advanced oxidation processes, although more efficient, may produce toxic by-products. Recent studies emphasize the importance of improved detection and monitoring techniques and advocate for stricter effluent regulations. Despite growing research attention, important knowledge gaps remain, including limited long-term field monitoring, insufficient data on environmentally realistic exposure scenarios, and incomplete assessment of transformation-product toxicity. Methods: The search strategy used the SCOPUS and PUBMED databases with the keywords "cephalosporin" AND "aquatic environment", resulting in 341 records. After applying predefined inclusion and exclusion criteria, 110 peer-reviewed English-language studies meeting predefined thematic inclusion criteria and relevant to the occurrence, environmental fate, ecotoxicological effects, antimicrobial resistance, and removal of cephalosporins in aquatic environments were included in the narrative synthesis. Results: The literature on cephalosporins in aquatic environments has expanded significantly from 1978 to 2025, prompted by concerns about pharmaceutical contamination and antibiotic resistance. Studies from 2016 to 2025 used advanced and multidisciplinary monitoring techniques, revealed key pollution sources such as wastewater treatment plants and hospitals, and correlated antibiotic residues with resistance genes, highlighting the need for continued monitoring and mitigation efforts. Ecotoxicological and fate studies further indicate that transformation processes may generate products with altered or increased toxicity, complicating environmental risk assessment. Conclusions: The literature shows increasing attention to cephalosporins in aquatic environments, reporting associations with antimicrobial resistance and adverse effects on aquatic organisms, including potential toxicity from transformation products. This review highlights the need for integrated monitoring, standardized toxicity assessment, and improved treatment strategies within a One Health framework.
The leishmaniases are a group of neglected tropical diseases caused by kinetoplastid protozoa of the genus Leishmania, transmitted by phlebotomine sandflies. In the absence of a human vaccine, current chemotherapeutic options remain suboptimal due to limited target selectivity, high cost, restricted availability in endemic low-resource regions, and escalating parasite resistance. This review highlights recent advances in rational drug design directed at the kinetoplast-a distinctive mitochondrial organelle critical for parasite viability. Different targets (e.g., kDNA, G-quadruplex, topoisomerases) and innovative approaches employing mitochondrion-targeted small molecules are discussed, as well as ligand-functionalized nanoparticle delivery systems that can transport bioactive agents to the parasite's mitochondrial microenvironment. These strategies highlight the kinetoplast's strong translational relevance as a selective antileishmanial target. By exploiting its unique molecular machinery, these strategies may offer improved parasite selectivity, although potential mitochondrial liabilities in host cells must be carefully evaluated.
Background: B7-H3, a type I transmembrane glycoprotein belonging to the B7 superfamily, is an attractive target for antitumor therapies. B7-H3 demonstrates aberrant overexpression in various types of solid tumors while showing limited and low expression in normal human organs. Various types of treatment targeting B7-H3 have been reported. Among these treatments, antibody-drug conjugates (ADCs) have shown potent activity, and several clinical trials, including DS7300a and MGC018, are currently ongoing. Methods: Here, we constructed CD276-8 ADC, composed of the anti-B7-H3 antibody CD276-8 with moderate affinity, an enzymatically cleavable tetra-peptide-based linker and DXd. Characteristics, including in vitro binding affinity and internalization activity, were assessed by bio-layer interferometry (BLI), flow cytometry and high content analysis (HCA). The cytotoxicity of CD276-8 ADC was evaluated in cell lines expressing B7-H3. Pharmacokinetic profiles and antitumor activity were evaluated in mouse models in vivo. Finally, the developability of CD276-8 ADC was assessed with plasma stability, accelerated stability and freeze-thaw studies using LC-MS and HPLC. Results: Characterization in vitro demonstrated the moderate affinity and acceptable internalization activity of CD276-8 ADC. In addition, CD276-8 ADC exhibited potent antitumor activities in B7-H3-positive cell line-derived xenograft (CDX) models with acceptable pharmacokinetic profiles, although it showed less potent cytotoxicity in various cell lines in vitro, indicating acceptable developability. Conclusions: We developed CD276-8 ADC, a B7-H3-targeting ADC with moderate affinity, which delivers the TOP1 inhibitor DXd. This design combined moderate affinity and acceptable pharmacokinetics, resulting in potent antitumor efficacy in vivo. Our study suggests that affinity optimization could be a useful consideration for enhancing ADC efficacy, positioning CD276-8 ADC as a promising therapeutic for B7-H3-expressing solid tumors.
Background: Viral infections represent a major challenge in modern medicine, including diseases caused by human papillomavirus (HPV), cytomegalovirus (CMV), and rotavirus, which are among the most prevalent viral pathogens. The rapid transmission and high mutation rates of these viruses contribute to substantial health burdens and socio economic consequences. Silver nanoparticles (Ag NPs) and titanium dioxide nanoparticles (TiO2-NPs) are effective antiviral agents. The major objective of this investigation was to measure the antiviral activity of titanium dioxide nanoparticles (TiO2-NPs) and green-produced silver nanoparticles (Ag NPs) against rotavirus, HPV, and CMV. Methods: UV-Vis spectroscopy, transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) were used to characterize the nanoparticles. Cytotoxicity and antiviral activity were evaluated using a crystal violet assay in infected cell cultures. Results: The main findings indicate that both Ag NPs and TiO2-NPs exhibited pronounced antiviral activity against HPV, CMV, and rotavirus. Ag NPs exhibited strong antiviral activity, with lower IC50 values against HPV and CMV; however, this effect was associated with lower cytotoxic concentration (CC50) and selectivity index (SI) values, indicating higher cytotoxicity. In contrast, TiO2-NPs demonstrated a favorable safety profile, as indicated by higher CC50 value particularly against CMV (863.90 µg/mL) and rotavirus (386.84 µg/mL)-and low cytotoxicity toward host cells-highlighting their strong antiviral selectivity and therapeutic potential. Conclusions: Overall, these findings suggest that, while Ag-NPs possess strong antiviral efficacy, TiO2 NPs offer a more balanced combination of antiviral effectiveness and biosafety and may therefore be more promising candidates for antiviral applications.
Flexible textile membranes were prepared by impregnating woven cotton fabrics with silicone oil (SO)-based suspensions containing carbonyl iron (CI) microparticles and iron oxide microfibers (μFe). The microfibers were obtained by a microwave-assisted microplasma process and then co-dispersed with CI in SO. In the final membranes, the CI content was kept constant at ΦCI=10 vol.%, whereas the microfiber fraction was 0, 10 and 20 vol.%. The resulting membranes were used as dielectric layers in planar capacitors and examined at 1 kHz under a static magnetic field of up to 150 mT and compressive pressure up to 10 kPa. In every composition, the capacitance rose with increasing magnetic flux density, but both the zero-field capacitance and the field-induced capacitance change became smaller as the microfiber content increased. A monotonic, nearly linear increase in capacitance was also observed under compression over the tested pressure range. Within a simplified parallel-plate and magnetic-stress analysis, the capacitance data were further used to estimate the apparent relative permittivity, together with capacitance-derived indicators of deformation and stiffness. These estimates suggest field-induced stiffening of the membranes and a higher apparent low-field stiffness at higher microfiber loading. The obtained hybrid CI/μFe-based textile membranes can serve as composition-tunable dielectric layers whose electrical response is influenced by both magnetic field and compressive loading, making them relevant for flexible capacitor-based elements.
Polyphenols have attracted considerable scientific interest over recent years due to their broad spectrum of biological activities, including antioxidant, cardioprotective, anti-inflammatory, antidiabetic, and anticancer properties. However, their practical application is often limited by unfavorable physicochemical characteristics, particularly low aqueous solubility. Consequently, amorphous solid dispersions (ASDs) have been extensively investigated as a formulation strategy to overcome these limitations. This article represents the first part of a two-part review and presents the current state of the art in amorphous solid dispersions of polyphenols. The available literature is systematically summarized with respect to the investigated polyphenolic compounds, the employed carriers (with particular emphasis on polymeric systems), the preparation methods, and the solid-state characterization techniques used to confirm amorphization. Both single-component systems and binary combinations of polyphenols reported in the literature are considered. The collected data are presented in tabular form and complemented by a heat map illustrating the frequency of reported polyphenol-carrier combinations. The aim of this review is to organize the available knowledge, identify the most extensively studied systems, and highlight research areas that remain underexplored. A detailed discussion of the pharmaceutical benefits and mechanistic aspects of polyphenols in ASD systems will be provided in Part II.
Background/Objectives: Variants of MYPN, encoding a sarcomeric protein myopalladin, are associated with different types of cardiomyopathies and myopathies. However, the molecular mechanisms of MYPN-associated pathologies are still poorly understood. Methods: In this study, we generated induced pluripotent stem cells (iPSCs) from a hypertrophic cardiomyopathy patient carrying a novel p.N989I (c.2966A>T) variant of MYPN and used iPSC-derived cardiomyocytes to examine the impact of the variant on biophysical characteristics and transcriptomic profile. Results: No significant changes in parameters of calcium transients, sodium current and action potential were found in iPSC-derived cardiomyocytes with the p.N989I (c.2966A>T) variant of MYPN compared to non-isogenic cells from an unrelated healthy donor. At the transcriptomic level, MYPN-N989I cardiomyocytes demonstrated an upregulation of genes linked to cell cycle, mitotic spindle, microtubule cytoskeleton organization, and myogenic program genes. Downregulation of sarcomeric, Z-disc- and cell junction-associated genes, as well as genes involved in ATP synthesis, oxidative phosphorylation, and the SRF-signaling pathway, was also revealed. Conclusions: Our data suggest that the p.N989I (c.2966A>T) variant of MYPN plays a dual role in hypertrophic cardiomyopathy pathogenesis, disrupting not only sarcomeric and cytoskeletal organization but also the regulation of the muscle gene program.
Ionizing radiation (IR) induces profound bone marrow (BM) injury by disrupting hematopoietic stem cell (HSC) homeostasis, leading to acute myelosuppression and long-term hematopoietic dysfunction. Although transcriptome-wide analyses have advanced our understanding of radiation responses, the key molecular networks and hub genes governing post-irradiation BM injury remain incompletely defined. This study aimed to systematically identify radiation-responsive pathways and central genes in BM after irradiation through an integrative bioinformatics approach based on RNA sequencing (RNA-seq). Public RNA-seq data from mouse BM HSCs collected 3 days after whole-body irradiation were analyzed. Differentially expressed genes (DEGs) were identified using two independent statistical frameworks to improve the robustness of the results. Functional analysis was performed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Protein-protein interaction (PPI) networks were constructed using STRING, and hub genes were identified using network topology parameters. Both analysis pathways consistently demonstrated extensive transcriptome reprogramming after irradiation. DEGs were primarily enriched in processes related to cytokine signaling, hematopoietic lineage regulation, immune response, and extracellular matrix remodeling. KEGG analysis highlighted cytokine-cytokine receptor interaction, hematopoietic cell lineage, JAK-STAT signaling, and PI3K-Akt signaling as key molecular axes. GSEA further supported coordinated changes in pathways related to inflammatory response, stress response, and metabolic reprogramming. PPI network analysis identified four consensus hub genes, namely Il6, Cd34, Gypa, and Pdgfrb, which are related to inflammatory signaling, hematopoietic regulation, erythroid dynamics, and microenvironmental remodeling, respectively. This integrative bioinformatics study demonstrates that radiation-induced BM injury is associated with coordinated activation of inflammatory cytokine networks, alterations in the hematopoietic program, and microenvironmental restructuring. The hub genes identified in this study may represent candidate regulatory genes or molecular indicators potentially involved in the response to radiation-induced hematopoietic damage.
Phyllanthus emblica (amla) exhibits anticancer activity, but its extracts often suffer from poor stability and bioavailability. This study developed amla extract-loaded niosomes to enhance delivery and evaluate their anticancer activity against MCF-7 and HCT116 cell lines, supported by in silico analyses. Methodology: Amla extract was prepared using a 50% aqueous-alcoholic solvent system and lyophilized. Niosomes were prepared by the thin-film hydration method and characterized for physicochemical properties. Anticancer activity was evaluated through in vitro cytotoxicity studies, supported by molecular docking and in silico pharmacokinetic analyses. Results: Optimized niosomes exhibited spherical morphology, good homogeneity (PDI < 0.30), anionic surface charge, high entrapment efficiency (70.5 ± 5.9%), and sustained diffusion-controlled release. In vitro cytotoxicity demonstrated a strong concentration-dependent anticancer activity of amla-loaded niosomes across a range of concentrations (31.25-1000 µg/mL) against both MCF-7 and HCT116 cell lines. At 1000 µg/mL, cell viability decreased to 7.0% and 5.4% in MCF-7 and HCT116 cells, respectively, with calculated IC50 values of 245 µg/mL and 158 µg/mL. Molecular docking and pharmacokinetic predictions supported the potential multi-target anticancer relevance of major phytochemicals, including hydrolyzable tannins, phenolic acids, flavonoid aglycones and glycosides, and highlighted bioavailability limitations for certain high-affinity glycosylated flavonoids, reinforcing the rationale for vesicular encapsulation. Conclusions: Amla extract-loaded niosomes represent a promising vesicular system for enhanced, sustained delivery of anticancer activity in vitro, with complementary in silico findings supporting mechanistic plausibility and translational rationale. Further studies are warranted to evaluate their performance in vivo.
Background: Dental caries, primarily caused by Streptococcus mutans (S. mutans), is a prevalent condition with significant global impact. Trans-cinnamaldehyde (TC), a phytochemical derived from the cinnamon plant, has shown promising antibacterial and antibiofilm activity against S. mutans. This study aimed to evaluate the anti-cariogenic effects of TC on S. mutans using an innovative mouse jaw explant model. Methods: TC was diluted in an organic solvent across various concentrations. Initially, cytotoxicity assays were performed at all tested TC concentrations. Sub-minimum bactericidal concentrations were then used to examine the distribution and morphology of S. mutans biofilms. Hemi-mandibles were dissected from euthanized, healthy, seven-week-old female mice to study the impact of TC on the cariogenic activity of S. mutans using stereoscopic analysis. Finally, pH changes during exposure to cariogenic conditions and post-treatment bacterial viability were measured. Results: In vitro data demonstrate that TC doses of ≤625 µg/mL were non-cytotoxic. Treatment groups exposed to TC exhibited altered bacterial morphology, including abnormal and incomplete cell division. In the mouse jaw explant model, TC doses of ≥625 µg/mL showed anti-cariogenic effects, evidenced by the absence of visible carious lesions. Additionally, pH changes and post-treatment viable bacterial counts corresponded with the observed anti-cariogenic activity. TC doses ≤625 µg/mL led to a pH drop over time and the presence of bacterial colonies. Conclusions: TC exhibits significant anti-cariogenic activity against S. mutans in the mouse model. Our findings suggest that 625 µg/mL is the lowest non-toxic concentration of TC that effectively inhibits cariogenic activity.
Background/Objectives: Poly(ADP-ribose) polymerase 1 (PARP1) is an important therapeutic target in DNA repair-deficient cancers, but discovery of new inhibitors remains constrained by scaffold convergence, tolerability limits, and acquired resistance. This study aimed to develop an interpretable, reliability-stratified cheminformatics workflow for PARP1 potency prioritization and structure-based follow-up. Methods: A curated ChEMBL dataset of 3339 PARP1 inhibitors was encoded using RDKit 2D descriptors and Avalon fingerprints (1143 initial features), then reduced to 132 informative variables by Random Forest-based feature selection. Five regression models were optimized, including a stacked ensemble. Model interpretation was performed using permutation feature importance and SHAP. External near-domain corroboration was assessed using a stringent PubChem similarity expansion (Tanimoto > 0.90) around sub-10 nM seed compounds, followed by comparison with retrievable experimental PARP1 activity values. Top scaffold-diverse candidates were further evaluated by complementary docking against PARP1 (PDB: 4R6E) using AutoDock Vina and cavity-guided docking through the SwissDock platform. Results: The stacked ensemble achieved the best held-out performance (test R2 = 0.723; RMSE = 0.610 pIC50 units), with 83.7% of test predictions within ≤0.75 pIC50 units and only 2.7% exceeding 1.5 pIC50 units. PubChem similarity expansion retrieved approximately 32,450 analogs, of which 3349 were predicted to have IC50 ≤ 10 nM. Among 366 compounds with retrievable experimental PARP1 activity values, predicted versus experimental pIC50 showed a positive association (R2 = 0.124; Pearson r = 0.479), with RMSE = 0.491 and MAE = 0.330 pIC50 units. Three ligands-CID 168873053, CID 175154210, and CID 172894737-showed the strongest complementary docking support and pocket-consistent poses relative to niraparib. Conclusions: This workflow provides a transparent and practically useful framework for near-domain PARP1 inhibitor prioritization. The combined QSAR, explainability, external corroboration, and docking strategy supports shortlist generation for experimental follow-up.
Background: Kleefstra syndrome (KS) is a rare neurodevelopmental disorder caused by haploinsufficiency of EHMT1; it is characterized by global developmental delay, intellectual disability, hypotonia, distinctive facial features, and variable congenital anomalies. Autistic features, behavioral abnormalities and severe speech impairment are frequently reported. However, molecularly confirmed cases of KS from Africa remain extremely limited, largely due to restricted access to genomic diagnostic infrastructures. Methods: We describe a 15-month-old patient from Rwanda presenting with neonatal hypotonia, global developmental delay, short stature, and characteristic dysmorphic facial features. Comprehensive clinical evaluation was performed, followed by trio-based exome sequencing to identify the underlying genetic cause of this neurodevelopmental disorder. Results: Exome sequencing identified a de novo heterozygous frameshift variant in EHMT1 (NM_024757.5: c.2871dup; p. Phe958Leufs*219), confirming the diagnosis of KS. Conclusions: This report presents the first molecularly confirmed case of KS in Rwanda. It highlights additional clinical features like bilateral 5th toe clinodactyly, short stature and absence of obesity in KS. There is a need to further delineate the study of EHMT1 and investigate the natural history of KS across different populations for optimal patient management and to reduce diagnostic odyssey. The diagnostic utility of exome sequencing for neurodevelopmental disorders needs to be strengthened, with strong emphasis on expanding genomic medicine to help diagnose rare diseases in resource-limited settings.