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Background/Objectives: Neuropathic pain remains a significant clinical challenge, with current treatments often providing inadequate relief and adverse effects. Sigma receptors (SRs) modulate nociception and have emerged as potential therapeutic targets for neuropathic pain. Although putative sigma-1 receptor (S1R) ligands have demonstrated analgesic efficacy in preclinical models, their in vivo efficacy and safety profiles require further clarification. Methods: Analogs of well-known selective S1R ligand UVM147 were synthesized using 3-component Ugi reactions and examined in vitro for receptor affinity in radioligand competition binding assays and in vivo with mouse models of neuropathic and inflammatory pain and adverse effects. Results: Three novel heterocyclic compounds (RO-4-3, RO-5-3, and RO-7-3) displayed in vitro nanomolar affinity with varying selectivity for both SR subtypes (S1R and S2R). When screened in vivo at a dose of 30 mg/kg s.c. in mice first subjected to chronic constriction injury (CCI), RO-5-3 and RO-7-3 possessed anti-allodynic potential, while UVM147 was inactive. Upon full characterization, RO-5-3 significantly attenuated mechanical allodynia in a dose-dependent manner, while RO-7-3 was ineffective at higher doses. Both compounds dose-dependently attenuated nociceptive behaviors in the mouse formalin assay. RO-5-3 induced mild respiratory depression without impairing locomotor activity, whereas RO-7-3 caused transient respiratory depression and locomotor impairment. Additionally, RO-5-3, but not RO-7-3, induced conditioned place aversion consistent with potential S2R involvement. Conclusions: RO-5-3 exerts antinociceptive and anti-allodynic effects with minimal adverse behavioral effects, supporting the role of SRs in pain modulation. These results add to growing evidence supporting the development of SR ligands as efficacious therapeutics for neuropathic pain with fewer clinical liabilities.

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Background/Objectives: The global fight against cancer persists despite advances in prevention and treatment. The current study investigated the phytochemical constituents, antioxidant, anti-inflammatory, and anticancer properties of Eucomis comosa, traditionally used in South Africa to treat elephantiasis and cancer-related conditions. Methods: Phytochemical screening, Fourier transform infrared spectroscopy (FTIR), and liquid chromatography-mass spectrometry (LC-MS) analyses were conducted. Antioxidant activity was measured through DPPH and nitric oxide (NO) radical scavenging assays. The anticancer activity was assessed using the MTT assay. Results: Phytochemical screening confirmed the presence of alkaloids, cardiac glycosides, terpenoids, flavonoids, saponins, and phlobatannins. FTIR analysis of the aqueous extract displayed characteristic peaks at 3278.92 cm^-1 for O-H stretch, at 2930.67 cm^-1 for C-H stretch, at 1623.97 cm^-1 for C=O stretch, 1410.24 cm^-1 for C=C stretch and at 931.17 cm^-1 for =C-H, while LC-MS identified diverse metabolites, including polyphenols such as flavan-3-ols, flavone glycosides, and chalcones. Among the extracts, methanol showed the strongest DPPH scavenging activity (IC₅₀ = 972.73 µg/mL), followed by ethanol (1296.36 µg/mL). For NO scavenging, methanol again outperformed ethanol, with IC₅₀ values of 1301 µg/mL and 2890 µg/mL, respectively. Cytotoxicity assays demonstrated that the ethanol extract completely inhibited cell growth at concentrations of 100 and 200 µg/mL. Methanol, ethanol, and hexane extracts significantly suppressed cell proliferation in DU-145, PC-3, and SKU-T-1 cancer cell lines at higher concentrations, with IC₅₀ values ranging between 0.2 and 2.5 µg/mL. Conclusions: These findings indicate that the phytochemicals and functional groups present in E. comosa extracts contribute to their dose-dependent antioxidant and anticancer activities, supporting their ethnomedicinal use.

Background/Objectives: The rapid development of biopharmaceuticals has heightened attention from both industry and regulatory agencies toward product quality, particularly regarding subvisible particles as a critical quality attribute. Existing pharmacopoeial methods, Light Obscuration (LO) and Microscopic Particle Count (MC), exhibit limitations in meeting increasingly refined analytical requirements. Flow Imaging Microscopy (FIM) technology shows promise as an alternative, yet its standardized methodologies are still under development. Methods: This study employed polystyrene microsphere standard beads and intravenous immunoglobulin to perform instrument standardization and consistency evaluations on FIM instruments sharing the same operating principles but from different manufacturers. The consistency and transferability of particle counting across platforms were assessed. Additionally, particle images obtained from parallel testing on two platforms were classified using confusion matrices based on convolutional neural networks and the Unified Manifold Approximation and Projection (UMAP) dimensionality reduction method. Results: This study investigated the consistency and developed a transfer strategy for particle counting results across different FIM platforms. Analysis of particle image classification confirmed the consistency of image-based categorization while also revealing the complexity associated with cross-platform image recognition. Conclusions: The findings provide valuable insights for the further standardization of Flow Imaging Microscopy, supporting its potential as a reliable analytical tool for subvisible particle analysis in biopharmaceutical quality control.

Background: Durvalumab consolidation following radiochemotherapy is now the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). [¹⁸F]FDG PET/CT offers valuable insights not just for staging but also for tumor characterization via radiomics, which can potentially predict histology, immunophenotype, and prognosis. Methods: We conducted a retrospective analysis of [¹⁸F]FDG PET/CT scans from stage IIIA-IIIB NSCLC patients treated at the Clinical Centre, University of Pécs. All biopsy samples were classified histologically (squamous vs. adenocarcinoma) and tested for PD-L1. Lung tumors were segmented using MEDISO InterViewTM FUSION software (version 3.12.002.0000). with an SUVmax threshold of four. Imaging features were extracted and compared based on histology, PD-L1 status, and neutrophil-to-lymphocyte ratio (NLR)-based prognosis groups. Statistical analyses were performed with Jamovi (v2.6.44), using Shapiro-Wilk, t-test/ANOVA, Mann-Whitney/Kruskal-Wallis, or Chi-square tests as appropriate. Results: Fifty-six patients were included (38 PD-L1-positive, 18 -negative). Among PD-L1-positive cases, poor versus good NLR prognosis groups differed in maximum diameter (p = 0.046), short-zone emphasis (p = 0.026), and zone-length non-uniformity (p = 0.027). Focusing on PD-L1-positive squamous carcinoma, maximum diameter, metabolic tumor volume, busyness, and coarseness showed significant differences (all p < 0.05). SUVmax, mean SUV, SUVpeak, and complexity were higher in squamous than in adenocarcinoma subtypes. PD-L1-positive and -negative squamous tumors differed in zone percentage (p = 0.039) and long-zone high gray-level emphasis (p = 0.024), while no significant differences were observed among adenocarcinomas. Conclusions: [¹⁸F]FDG PET/CT radiomics showed potential for differentiating NSCLC histological subtypes and for identifying PD-L1-associated imaging patterns in squamous cell carcinoma. In addition, certain metabolic features were associated with NLR-based prognostic groups in PD-L1-positive patients.

Background/Objectives: Metabolic syndrome (MetS) is a group of cardiometabolic risk factors whose current management relies on lifestyle changes and pharmacological interventions, frequently involving multiple medications. Therefore, the demand for therapies capable of delivering comprehensive management of MetS is increasing. In this context, nutraceuticals such as celery seed have attracted increasing scientific interest. This study aimed to evaluate the effect of celery seed (Apium graveolens L.) administration on the components of MetS, insulin sensitivity, and insulin secretion. Methods: A randomized, double-blind, placebo-controlled clinical trial was carried out in 28 patients with MetS. Fourteen patients randomly received celery seed (150 mg/day) for 12 weeks, and 14 subjects received a placebo. Clinical and laboratory determinations were evaluated at baseline and the end of the study. Results: After celery seed administration, patients showed a significant decrease in their systolic blood pressure (SBP) (121.0 ± 9.7 mmHg vs. 115.7 ± 12.8 mmHg, p = 0.005), diastolic blood pressure (DBP) (82.2 ± 5.9 mmHg vs. 78.5 ± 8.6 mmHg, p = 0.013), triglycerides (TG) (2.3 ± 0.9 mmol/L vs. 1.8 ± 0.6 mmol/L, p = 0.016), very low-density lipoprotein (VLDL) (0.4 ± 0.1 mmol/L vs. 0.3 ± 0.1 mmol/L, p = 0.016) and uric acid (297.4 ± 53.5 µmol/L vs. 261.7 ± 53.5 µmol/L, p = 0.009). Insulin sensitivity and insulin secretion showed no statistically significant differences in the celery seed group. Conclusions: Celery seed administration significantly reduced SBP, DBP, TG, VLDL, and uric acid. The protocol was registered at ClinicalTrials.gov with the identifier NCT06061926.

Background: Autism spectrum disorder (ASD) represents a major challenge in neurological development research and is receiving increasing attention from the pharmacological and pharmaceutical sciences. Despite this constant growth, there is no document that provides a comprehensive overview integrating publication trends, key contributors, and thematic developments, allowing efforts to be focused on specific areas. Objective: To conduct a comprehensive bibliometric analysis of pharmacological research related to ASD published between 2001 and 2025. Methods: The database obtained contains 1170 articles indexed in the Web of Science (WoS) database in the JCR Pharmacy and Pharmacology category. Bibliometric indicators such as publication growth, h-index, authorship, institutional and national productivity, and keyword co-occurrence were analyzed using VOSviewer and the laws of Price, Bradford, Zipf, and Lotka. Results: A total of 1170 documents were analyzed, showing an exponential increase in pharmacological research related to ASD over the last two decades. The United States, China, and Italy emerged as the most productive countries, while King Saud University, Harvard Medical School, and The Ohio State University were among the leading institutions. The most frequently cited keywords, such as "autism spectrum disorder," "valproic acid," "oxidative stress," and "flavonoids," revealed a translational approach linking neurobiological mechanisms, redox imbalance, and therapeutic interventions. Contemporary research emphasizes immuno-synaptic interactions, microbiota, and biomarker-guided approaches. Conclusions: This study highlights the global expansion and diversification of pharmacological research in ASD. The results underscore a shift toward integrated biological frameworks and precision-oriented strategies, reinforcing the need for interdisciplinary collaboration to advance translational outcomes in ASD therapy.

Background: The traditional formula Liqi Yangyin (LQYY) has shown clinical and preclinical efficacy for depression with constipation, yet its molecular mechanisms remain incompletely defined. This study aimed to elucidate its mechanisms using an integrative approach. Methods: Constituents of LQYY were profiled by UPLC-MS/MS and integrated with network pharmacology and molecular docking to identify brain-accessible components and putative targets. A chronic unpredictable mild stress (CUMS) model was used for experimental validation. Outcomes included behavioral tests (sucrose preference test, open field test, and forced swimming test), gastrointestinal indices, including fecal water content, time of first black stool, and intestinal propulsion rate, histopathology of the prefrontal cortex (PFC) and colon, TUNEL staining, NeuN immunofluorescence, Western blotting, and qRT-PCR. Results: LQYY attenuated CUMS-induced weight loss and depressive-like behaviors and improved intestinal transit metrics. It reduced neuronal apoptosis in the PFC and ameliorated colonic injury. Mechanistically, docking and enrichment analyses highlighted hub targets (STAT3, AKT1, ESR1, IL-6, TNF, TP53) and the JAK/STAT pathway. In vivo, LQYY decreased IL-6, TNF-α, ESR1, TP53, and STAT3, and increased AKT1 in the PFC and colon; it also reduced the TUNEL-positive rate and restored NeuN labeling, upregulated Bcl-2, and downregulated p-JAK2/JAK2 and p-STAT3/STAT3 ratios, and the expression of Bax and cleaved-caspase-3 in the PFC, consistent with the suppression of pro-inflammatory and apoptotic signaling. Conclusions: LQYY exerts antidepressant and pro-motility effects in CUMS mice by modulating JAK2/STAT3-centered networks and inhibiting neuronal apoptosis, thus supporting a multi-component, multi-target strategy for treating depression with constipation, and providing a defined molecular hypothesis for future investigation.

Objective: Echinacea purpurea, an herb with diverse pharmacological activities, has its roots widely used for anti-inflammatory and immunomodulatory purposes. Interestingly, its aerial parts, which are also rich in bioactive compounds, remain underutilized. This study aims to optimize the extraction and purification processes to obtain the aerial part extract of Echinacea purpurea (APE-EP) to enhance the content of active constituents and improve its anti-inflammatory and immunomodulatory effects. Methods: We analyzed the chemical composition of APE-EP using HPLC-MS. The intestinal absorption characteristics of APE-EP were evaluated using an ex vivo everted gut sac assay. Furthermore, the anti-inflammatory and immunomodulatory effects of APE-EP were validated using a DSS-induced colitis mouse model. Results: Several phenolic acids were identified, including chicoric acid and caffeic acid, which have significant antioxidant and anti-inflammatory activities. The everted gut sac assay revealed concentration-dependent absorption of chicoric acid in the gut. Results from the mouse model showed that APE-EP promoted macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 macrophages at the lesion sites, effectively suppressing inflammation and alleviating colitis-related pathological damage. Conclusions: This study enhances the medicinal value of the E. purpurea, provides new insights for the efficient utilization of plant resources, and offers a potential natural drug candidate for inflammatory bowel disease treatment.

Background/Objectives: Oral squamous cell carcinoma (OSCC) remains a major therapeutic challenge due to treatment-related toxicity and impaired oral tissue regeneration. This study aimed to develop and characterize a novel biocomposite based on bioactive compounds from Ganoderma lucidum incorporated into marine collagen derived from Rhizostoma pulmo and to evaluate its physicochemical properties, antioxidant and antimicrobial activities, and in vitro antitumor potential in the oral cavity. Methods: Hydroalcoholic extracts of G. lucidum and pepsin-soluble collagen peptides from R. pulmo jellyfish were prepared and combined to obtain two hydrogel biocomposites with different component ratios. Chemical and structural characterization was performed using HPLC-DAD, SDS-PAGE, FT-IR, circular dichroism, and spectrophotometric assays. Antioxidant activity was assessed by DPPH radical scavenging and reducing power assays, while antimicrobial activity was evaluated against oral pathogens using diffusion and MIC methods. In vitro biological activity was investigated using MTT viability and scratch migration assays on human OSCC cell lines (SCC-9 and HSC-3). Results: The biocomposites preserved the structural integrity of type I collagen and incorporated polysaccharides and polyphenols from G. lucidum. The combined formulations showed enhanced antioxidant and antimicrobial activities compared with collagen alone. In vitro assays demonstrated dose- and time-dependent reductions in OSCC cell viability and delayed cell migration, with effects comparable to those of G. lucidum extract. Conclusions: The G. lucidum-R. pulmo biocomposite exhibits favorable physicochemical properties and demonstrates antioxidant, antimicrobial, and in vitro antitumor activity. These findings support its potential as a multifunctional biomaterial for further investigation as an adjunct approach in oral cancer-related applications.