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32 pages, 11863 KB  
Review
Molecular and Cellular Mechanisms of Synaptogenesis and Synaptic Refinement During Cerebellar Circuit Formation
by Farshid Ghiyamihoor, Azam Asemi Rad and Hassan Marzban
Int. J. Mol. Sci. 2026, 27(17), 7576; https://doi.org/10.3390/ijms27177576 - 24 Aug 2026
Abstract
Interactions among molecular recognition systems, neuronal activity, and glial regulation transform early neuronal connectivity into precise functional circuits during brain development. The cerebellum is a powerful model for studying these mechanisms due to its stereotyped and accessible circuitry. Two major excitatory afferent pathways—climbing [...] Read more.
Interactions among molecular recognition systems, neuronal activity, and glial regulation transform early neuronal connectivity into precise functional circuits during brain development. The cerebellum is a powerful model for studying these mechanisms due to its stereotyped and accessible circuitry. Two major excitatory afferent pathways—climbing fibers (CFs), which convey error-related signals to Purkinje cells (PCs), and mossy fibers (MFs), which transmit sensorimotor information via granule cells (GCs) and parallel fibers (PFs)—undergo strengthening, competition, and refinement during postnatal development. Synaptic specificity is established by general and pathway-specific organizers. The neurexin–neuroligin system broadly regulates synapse formation, while the neurexin–CBLN1–GluD2 complex specifies PF–PC synapses and C1qL1–BAI3 signaling stabilizes the dominant CF input during competitive refinement. CF–PC synapse elimination serves as a classic model of activity-dependent competition, where weaker inputs are removed through calcium-dependent mechanisms. In parallel, glial cells regulate synaptic maturation: microglia shape inhibitory environments, and Bergmann glia support glutamate homeostasis, dendritic organization, and synapse stability. PCs integrate CF and PF inputs and provide inhibitory output to the cerebellar nuclei, where convergent excitatory collaterals from CFs and MFs are combined with PC inhibition to generate cerebellar output. Together, these coordinated molecular, cellular, and circuit-level mechanisms establish the synaptic architecture underlying cerebellar computation, motor coordination, and adaptive learning, which are the central focus of this review. Full article
(This article belongs to the Special Issue Recent Research in Cerebellar Development and Disease)
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14 pages, 6831 KB  
Article
Enhydrin Exhibits Antitumor Effects on Human Prostate Cancer Cells Associated with Reduced PI3K/AKT- and NF-κB-Related Gene and Protein Expression
by Xia Zhang, Rikiya Taoka, Dage Liu, Hirohito Naito, Yohei Abe, Akram Hossain and Mikio Sugimoto
Curr. Issues Mol. Biol. 2026, 48(8), 851; https://doi.org/10.3390/cimb48080851 - 21 Aug 2026
Viewed by 63
Abstract
Enhydrin, a melampolide-type sesquiterpene lactone abundant in the leaves of yacon (Smallanthus sonchifolius), has not previously been investigated for its anti-prostate cancer activity. This study investigated the antiproliferative effects of enhydrin in human prostate cancer cells, its regulatory effects on apoptosis-related [...] Read more.
Enhydrin, a melampolide-type sesquiterpene lactone abundant in the leaves of yacon (Smallanthus sonchifolius), has not previously been investigated for its anti-prostate cancer activity. This study investigated the antiproliferative effects of enhydrin in human prostate cancer cells, its regulatory effects on apoptosis-related molecules, and its impact on the PI3K/AKT and NF-κB signaling pathways. Three prostate cancer cell lines (PC3, DU145, and LNCaP) were treated with enhydrin, and its effects were analyzed using cell viability assays, morphological observation, flow cytometry, apoptosis-focused TaqMan qPCR array, qRT-PCR, and Western blotting. In vivo antitumor activity was assessed in a PC3 xenograft mouse model. Enhydrin reduced cell viability in a dose- and time-dependent manner, induced morphological changes associated with cytotoxicity, and caused G1 cell-cycle arrest. Gene expression analysis revealed downregulation of PI3K/AKT- and NF-κB-related genes and modulation of BCL2 family genes toward a pro-apoptotic profile, which was confirmed at both mRNA and protein levels. In vivo, enhydrin suppressed tumor growth without significant body-weight loss. These findings suggest that enhydrin exerts antitumor effects in prostate cancer by reducing the expression of PI3K/AKT and NF-κB related molecules and modulating apoptosis-related proteins. Although additional studies are required to determine pathway activity, directly confirm apoptosis, and evaluate normal-cell cytotoxicity and the therapeutic window, these findings provide preliminary biological evidence of the effects of enhydrin in prostate cancer models. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Cancer Treatment and Anticancer Drugs)
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24 pages, 9858 KB  
Article
Calibrated Optoelectronic TCAD Optimization of All-Organic and Hybrid Organic/Crystalline Silicon Two-Terminal Tandem Solar Cells
by Mahmoud Fathy, H. M. Hashem, Medhat Ammar, Mohamed Okil, Ahmed Shaker, Michael Gad and A. E. Hassanien
Crystals 2026, 16(8), 545; https://doi.org/10.3390/cryst16080545 - 20 Aug 2026
Viewed by 111
Abstract
The increasing demand for high-efficiency photovoltaic technologies has intensified research into tandem solar cells (TSCs) as a promising strategy to surpass the performance limits of single-junction devices. In this study, a comprehensive optoelectronic simulation using a Silvaco ATLAS TCAD simulator is employed to [...] Read more.
The increasing demand for high-efficiency photovoltaic technologies has intensified research into tandem solar cells (TSCs) as a promising strategy to surpass the performance limits of single-junction devices. In this study, a comprehensive optoelectronic simulation using a Silvaco ATLAS TCAD simulator is employed to design, optimize, and compare two tandem architectures: all-organic and hybrid organic/silicon TSCs. The all-organic configuration consists of polymer donors comprising a PBDB-T:F-M top sub-cell stacked with a PTB7-Th:COi8DFIC:PC71BM bottom sub-cell, while the hybrid configuration integrates a PBDB-T:F-M organic top cell with a crystalline Si bottom cell. Calibrated device models, validated against experimental data of the individual sub-cells, are used to evaluate tandem performance and guide systematic optimization. The two tandem architectures employ the same PBDB-T:F-M wide-bandgap organic top absorber (Eg~1.60 eV), while the rear sub-cell consists of either the PTB7-Th:COi8DFIC:PC71BM organic absorber (Eg~1.20 eV) or crystalline silicon (Eg~1.12 eV). The initial organic/organic tandem device accomplishes a power conversion efficiency (PCE) of 15.70% and JSC of 10.96 mA/cm2, whereas the organic/silicon tandem structure exhibits a higher initial PCE of 16.85% and JSC of 12.26 mA/cm2. Following absorber-thickness optimization, the all-organic and hybrid OSC/Si tandems achieve PCEs of 19.44% and 21.13%, respectively. Rather than constituting a simple efficiency ranking, the comparison reveals distinct optical, electrical, and technological trade-offs. The hybrid architecture benefits from the broader spectral utilization and efficient carrier collection of thin crystalline Si, whereas the all-organic configuration offers advantages associated with low-temperature solution processing, reduced material consumption, and potentially fully solution-processed photovoltaic fabrication. The calibrated comparative framework therefore provides design guidance for selecting and optimizing TSCs according to both performance and application requirements. Full article
(This article belongs to the Section Organic Crystalline Materials)
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22 pages, 8799 KB  
Article
CD47 Aptamer-Decorated Fluorescent POSS Hybrid Nanoparticles as a Biohybrid Interface for Probing Prostate Cancer–Macrophage Interactions
by Sumeyye Altunok, Gunes Kibar, Fatma Aylaz, Dide Su Demirel and Veli Cengiz Ozalp
Biomimetics 2026, 11(8), 588; https://doi.org/10.3390/biomimetics11080588 - 18 Aug 2026
Viewed by 357
Abstract
Prostate cancer remains a major clinical challenge, partly due to tumour–immune interactions that contribute to immune evasion and therapeutic resistance. The CD47–SIRPα axis is a key macrophage-associated immune recognition pathway; and materials-oriented platforms that allow preliminary investigation of tumour–macrophage interaction patterns remain valuable. [...] Read more.
Prostate cancer remains a major clinical challenge, partly due to tumour–immune interactions that contribute to immune evasion and therapeutic resistance. The CD47–SIRPα axis is a key macrophage-associated immune recognition pathway; and materials-oriented platforms that allow preliminary investigation of tumour–macrophage interaction patterns remain valuable. Here, we report an optically traceable biohybrid nanoplatform based on CD47 aptamer-functionalized fluorescent carboxyl-functional MMES-POSS hybrid nanoparticles. The nanoparticles were synthesized within 5 min using UV-induced free-radical emulsion polymerization in an ethanol–water system and exhibited spherical morphology, SEM-derived dry-state mean diameters below 100 nm, negative surface charge, and retained fluorescence due to RITC encapsulation within the crosslinked hybrid matrix; however, DLS measurements revealed pronounced aggregation and polydispersity in aqueous dispersion. SEM and EDX provided complementary evidence of nanoparticle morphology and elemental composition, whereas zeta potential and Nanodrop measurements provided evidence consistent with surface functionalization, and FTIR confirmed retention of the core POSS, carbonyl, and RITC-associated chemistry. In a PC-3/THP-1 macrophage co-culture model, Annexin V–FITC/PI flow cytometry showed a concentration-dependent redistribution of cell populations, with the most pronounced early apoptotic enrichment observed at 2 µg/mL. However, pairwise exploratory comparisons among concentrations did not reach statistical significance, and this is discussed as a limitation of the present exploratory dose–response characterization. These findings indicate preliminary interaction-associated response patterns rather than definitive receptor-specific targeting or therapeutic CD47–SIRPα blockade. Overall, this modular POSS-based biohybrid interface provides a materials-oriented platform for probing prostate cancer–macrophage interaction profiles and guiding future mechanistic validation studies. Full article
(This article belongs to the Section Biomimetics of Materials and Structures)
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21 pages, 4794 KB  
Article
Integrated Metabolomics, Network Pharmacology, and Molecular Dynamics Simulations Reveal the Potential Anti-Melanoma Mechanisms of Inonotus hispidus
by Hui Liu, Jihao Liu, Zuohao Ma, Hao Li, Xinli Liu and Deqiang Zhu
Curr. Issues Mol. Biol. 2026, 48(8), 814; https://doi.org/10.3390/cimb48080814 - 12 Aug 2026
Viewed by 180
Abstract
Melanoma is a highly aggressive malignancy characterized by pronounced metastatic potential, marked heterogeneity, and complex therapeutic resistance. Although immunotherapy and targeted therapy have improved the prognosis of some patients, their long-term clinical application remains constrained by limited therapeutic responses, drug resistance, and adverse [...] Read more.
Melanoma is a highly aggressive malignancy characterized by pronounced metastatic potential, marked heterogeneity, and complex therapeutic resistance. Although immunotherapy and targeted therapy have improved the prognosis of some patients, their long-term clinical application remains constrained by limited therapeutic responses, drug resistance, and adverse effects. In this study, widely targeted metabolomics, network pharmacology, molecular docking, and molecular dynamics simulations were integrated to systematically investigate the potential mechanisms underlying the anti-melanoma effects of Inonotus hispidus SH-18. Fruiting bodies of Sang Huang at the Juvenile, Growth, and Maturation stages were analyzed using UPLC-MS/MS, identifying 1575 metabolites across 13 chemical classes. PCA explained 67.91% of the total variance (PC1, 43.54%; PC2, 24.37%), while the OPLS-DA models yielded Q2 values of 0.964, 0.966, and 0.981 for IH-G vs. IH-J, IH-M vs. IH-G, and IH-M vs. IH-J, respectively. A total of 1099 differentially accumulated metabolites were identified, including 304 (140 up-accumulated and 164 down-accumulated), 311 (195 up-accumulated and 116 down-accumulated), and 484 (278 up-accumulated and 206 down-accumulated) in the three respective comparisons. Based on the experimentally detected metabolites, network pharmacology and bioinformatics analyses suggested that the active constituents of Sang Huang may synergistically suppress melanoma cell proliferation, survival, immune evasion, angiogenesis, invasion, and metastasis by regulating multiple pathways and signaling axes, including the TP53-p21 axis. Molecular docking showed that the candidate active compounds exhibited binding potential with core targets, among which ursolic acid displayed favorable binding capacity toward all core targets. Molecular dynamics simulations further supported the stability of these interactions. Notably, ursolic acid was most abundant in samples from the Juvenile stage, suggesting that this stage may be preferred for ursolic acid enrichment and subsequent activity evaluation. These findings suggest the potential therapeutic value of Sang Huang in melanoma treatment. Full article
(This article belongs to the Section Bioinformatics and Systems Biology)
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19 pages, 4046 KB  
Article
BoDV-1 Infection Is Associated with Altered Prion Protein Glycoform Maturation and Reduced ETS1-MGAT5/GnTV Pathway Activity in Rat C6 Astroglial Cells
by Akikazu Sakudo and Kazuyoshi Ikuta
Microorganisms 2026, 14(8), 1759; https://doi.org/10.3390/microorganisms14081759 - 10 Aug 2026
Viewed by 210
Abstract
Borna disease virus 1 (BoDV-1) is a noncytolytic, neurotrophic virus that causes neurological disorders, where astrocytes contribute to neuropathology. Cellular prion protein (PrPC) is involved in pro-survival signaling and antioxidative defense. Using rat astroglial C6 cells as an in vitro model, [...] Read more.
Borna disease virus 1 (BoDV-1) is a noncytolytic, neurotrophic virus that causes neurological disorders, where astrocytes contribute to neuropathology. Cellular prion protein (PrPC) is involved in pro-survival signaling and antioxidative defense. Using rat astroglial C6 cells as an in vitro model, we investigated whether persistent BoDV-1 infection alters N-glycan maturation of PrPC. Western blotting showed that PrPC shifted toward lower-molecular-weight glycoforms as cell density increased. This tendency was more evident in BoDV-1-infected C6 cells without detectable changes in total surface PrPC expression. Two-dimensional polyacrylamide gel electrophoresis showed a shift of PrPC toward lower molecular weight and more basic isoelectric points. Conventional RT-PCR detected reduced signals of MGAT5, which encodes N-acetylglucosaminyltransferase V (GnTV), whereas MGAT1–4 signals were not markedly altered. In addition, GnTV overexpression induced a higher-molecular-weight shift of PrPC. PHA-L4 precipitation followed by anti-PrP immunoblotting showed reduced β1-6-branched complex N-glycan signals associated with PrPC. BoDV-1 infection also decreased the RT-PCR signal of E26 transformation-specific 1 (ETS1) as well as reduced ETS-dependent promoter activity and superoxide dismutase activity. These findings suggest that persistent BoDV-1 infection may impair PrPCN-glycan maturation through suppression of the ETS1–MGAT5/GnTV pathway activity, thereby potentially affecting astroglial antioxidative capacity. Full article
(This article belongs to the Section Public Health Microbiology)
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20 pages, 12687 KB  
Article
Genome-Wide Association Study and Genomic Selection for Average Daily Gain in Ashidan Yak
by Zhicheng Wang, Xiaoming Ma, Guangwei Hu, Jianwu Jing, Yongfu La, Wenwen Ren, Baicheng Zhou, Hongkang Li, Min Chu, Xiaoyun Wu, Ping Yan, Xian Guo and Chunnian Liang
Animals 2026, 16(16), 2452; https://doi.org/10.3390/ani16162452 - 7 Aug 2026
Viewed by 286
Abstract
Average daily gain (ADG) is a core quantitative trait determining the economic benefits of Ashidan yak, a polled new breed adapted to cold barn feeding on the Qinghai–Tibet Plateau. Unraveling its complex genetic architecture is crucial for early molecular breeding selection. In this [...] Read more.
Average daily gain (ADG) is a core quantitative trait determining the economic benefits of Ashidan yak, a polled new breed adapted to cold barn feeding on the Qinghai–Tibet Plateau. Unraveling its complex genetic architecture is crucial for early molecular breeding selection. In this study, high-depth whole-genome resequencing (WGS) data from 474 Ashidan yaks were used to conduct combined evaluation of genome-wide association study (GWAS) and genomic selection (GS). During GWAS analysis, sex and measurement batch were included as fixed effects, while birth weight and principal components (PC1–PC3) were incorporated as covariates. Multi-model association analysis using GLM, MLM, and FarmCPU was performed on 3.36 million LD-pruned SNPs. The genomic inflation factors (λ ≈ 1.0) for MLM and FarmCPU confirmed effective elimination of population stratification. A total of 11 genome-wide significant SNP loci and 7 key candidate genes including PDE10A, RAD51B, BCAS3 and KCNH8 were identified via the FarmCPU model. Functional enrichment analysis indicated that these gene clusters are significantly involved in cAMP signaling pathway, regulation of ion channel activity, as well as extracellular matrix remodeling of blood vessels and skeletal muscle cells. For genomic selection, a single-trait GBLUP model was constructed using 22.87 million high-density raw SNPs to fully capture polygenic minor effects. Moderately high narrow-sense genomic heritability of ADG was estimated at h2 = 0.3233 (p < 0.05). The average independent prediction accuracy across the 10-fold cross-validation reached an average of R = 0.14 ± 0.07. To evaluate marker prioritized genomic evaluation without data leakage, a strict 10-fold cross-validation scheme was implemented, where the top 1% high-priority variant set (~228,000 SNPs) was screened independently within each training fold. The resulting unbiased prediction accuracy reached R = 0.1328 ± 0.1566 (with an average RMSE of 0.3793 ± 0.0066 and a regression slope of 0.4183 ± 0.5055). Comparing this with the unselected whole-genome baseline (R = 0.14 ± 0.07) indicates that naive marker selection based solely on GBLUP effect size in small reference cohorts is influenced by sampling variance, highlighting the need to integrate multi-omics functional annotations for future custom breeding array development. This study provides quantitative insights into the polygenic architecture of ADG in yaks, offering baseline data for genomic selection and custom array development for indigenous livestock on the Qinghai–Tibet Plateau. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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48 pages, 35599 KB  
Article
LightBAL: An AI-Based Model for EfficientActive Balancing in Electric Vehicle Battery Management Systems
by Khayri Abu Sayf, Main Hammad Nazir, Leshan Uggalla and Abdulla Rahil
Batteries 2026, 12(8), 287; https://doi.org/10.3390/batteries12080287 - 5 Aug 2026
Viewed by 316
Abstract
In this paper, we present LightBAL, an ultra-lightweight deep learning framework for real-time active cell balancing and onboard balancing control in electric vehicle (EV) battery management systems (BMSs). Although active cell balancing can improve battery utilisation and performance, applying deep learning-based balancing control [...] Read more.
In this paper, we present LightBAL, an ultra-lightweight deep learning framework for real-time active cell balancing and onboard balancing control in electric vehicle (EV) battery management systems (BMSs). Although active cell balancing can improve battery utilisation and performance, applying deep learning-based balancing control strategies remains prohibitive in typical embeddable BMS platforms because of the computational complexity and inference latency of deep models. In response to this issue, we propose an AI-physics-informed controller that forecasts the voltage difference of a single cell, the SoC variation, and the optimal balancing current based on proportional feedback closed-loop (FCLL) control. The introduced framework exploits wavelet-based adaptive denoising, multi-scale hierarchical feature learning using a cooperative Principal Component Analysis (PCA) and autoencoder feature extraction technique, and a lightweight One-Dimensional Convolutional Neural Network (Conv1D) coupled with Bidirectional Long Short-Term Memory (BiLSTM) (Conv1D-BiLSTM). The implemented lightweight network is further trained by model compression methodologies such as knowledge distillation and 8-bit quantisation-aware training, aiming for efficient deployment on edge devices. Experimental validation on the multivariate battery time-series dataset demonstrates that LightBAL achieves an F1-score of 96.64%, a balancing efficiency of 94.30%, and a Mean Absolute Error (MAE) of 0.0379, outperforming methods based on conventional ANN, LSTM, and CNN. LightBAL without compression takes only 1.26 s to conclude on a PC workstation; the inference latency of the embedded light model is as low as 28.7 ms. In addition, hardware-in-the-loop (HIL) validation on the Raspberry Pi 4 platform indicates that the framework can fulfil real-time inference requirements under normal operating conditions, taking 28.7 ms per balancing process. Simulation shows that the proposed approach significantly decreases cumulative balancing energy loss by 12.4% across several driving cycle conditions. Full article
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28 pages, 13658 KB  
Article
Transferrin-Conjugated, Camptothecin-Bearing Dendrimersomes Entrapping Docetaxel as a Dual-Drug Nanoplatform for Targeted Prostate Cancer Therapy
by Musa Albatsh, Zainab Al-Quraishi, Partha Laskar, Sukrut Somani, Craig Irving, Graeme R. Mackenzie, Stuart Woods, Craig W. Roberts, Margaret Mullin and Christine Dufès
Pharmaceutics 2026, 18(8), 959; https://doi.org/10.3390/pharmaceutics18080959 - 4 Aug 2026
Viewed by 264
Abstract
Background/Objectives: Advanced prostate cancer remains difficult to treat because docetaxel, although clinically important, is limited by systemic toxicity, poor tumor selectivity, and acquired resistance. Camptothecin is a potent anticancer agent, but its clinical application is restricted by poor solubility and instability. This [...] Read more.
Background/Objectives: Advanced prostate cancer remains difficult to treat because docetaxel, although clinically important, is limited by systemic toxicity, poor tumor selectivity, and acquired resistance. Camptothecin is a potent anticancer agent, but its clinical application is restricted by poor solubility and instability. This study investigated the synergy between docetaxel and camptothecin and developed transferrin-conjugated, camptothecin-bearing dendrimersomes entrapping docetaxel as a targeted nanocarrier for prostate cancer therapy. Methods: Drug synergy was evaluated in PC3-Luc cells using an MTT assay and combination index analysis. Transferrin-conjugated, disulfide-linked camptothecin-bearing PEGylated DAB dendrimers were synthesized and characterized by 1H-NMR, critical aggregation concentration analysis, transmission electron microscopy, and entrapment efficiency measurements. pH- and redox-dependent drug release was assessed by dialysis. Cellular uptake and uptake mechanisms were investigated by confocal microscopy, flow cytometry, and inhibitor studies in PC3-Luc, DU145, and LNCaP cells. Anti-proliferative efficacy was determined by an MTT assay. Results: Docetaxel and camptothecin showed marked synergy in PC3-Luc cells, with a minimum combination index of 0.20 ± 0.01 and 88.10 ± 0.41% growth inhibition at low nanomolar concentrations. Transferrin-conjugated dendrimersomes self-assembled into spherical vesicles with a critical aggregation concentration of approximately 250 µg/mL. They had high docetaxel entrapment efficiency (89.10 ± 0.08%) and enhanced drug release under acidic and reductive conditions. They significantly increased cellular uptake of docetaxel relative to non-targeted dendrimersomes (by up to 3-fold) and free drugs (by up to 20-fold), mainly through transferrin receptor-mediated endocytosis, and improved anti-proliferative activity in all three cell lines. Tf-conjugated DPSSC produced the lowest IC50 values among the tested formulations: 11.72 ± 1.02 nM in PC3-Luc, 9.88 ± 1.22 nM in DU145, and 7.88 ± 1.35 nM in LNCaP cells. Conclusions: Transferrin-conjugated camptothecin-based dendrimersomes entrapping docetaxel represent a promising multifunctional nanocarrier for prostate cancer that combines synergistic dual-drug therapy, active targeting, and stimulus-responsive release, supporting further evaluation as a selective delivery strategy in advanced prostate cancer using preclinical models and in vivo studies. Full article
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15 pages, 23979 KB  
Article
In Vitro Evaluation of Electroactive GelMA/PCL/Graphene Oxide Scaffolds for Peripheral Nerve Repair
by Yingcong He, Ruiqiang Chen, Shuangqi Gao, Jie Pan, Wei Zhang, Shulin Bai, Peixun Zhang and Xingxing Fang
J. Funct. Biomater. 2026, 17(8), 376; https://doi.org/10.3390/jfb17080376 - 3 Aug 2026
Viewed by 275
Abstract
This study developed electroconductive GelMA/PCL/graphene oxide (GO) nanofibrous scaffolds and performed a preliminary in vitro evaluation for peripheral nerve repair, focusing on optimizing the GO concentration. GO (0.1–1.0 wt%) was incorporated into GelMA/PCL via electrospinning. The 1.0 wt% GO scaffold exhibited reduced fiber [...] Read more.
This study developed electroconductive GelMA/PCL/graphene oxide (GO) nanofibrous scaffolds and performed a preliminary in vitro evaluation for peripheral nerve repair, focusing on optimizing the GO concentration. GO (0.1–1.0 wt%) was incorporated into GelMA/PCL via electrospinning. The 1.0 wt% GO scaffold exhibited reduced fiber diameters (200–300 nm) and enhanced electrical conductivity (8.4 × 10−4 mS/cm). All scaffolds were superhydrophilic (contact angle ≈ 0°). Tensile strength and fracture strain increased up to 0.5 wt% GO but decreased at 1.0 wt% GO to levels not significantly different from those of the control. PC12 cells demonstrated robust adhesion, proliferation, and viability on all scaffolds. Under electrical stimulation (100 mV/cm), the 1.0 wt% GO scaffold promoted qualitative axonal elongation and directional alignment compared with scaffolds lacking GO or subjected to no electrical stimulation. Scaffold-immobilized GO showed no cytotoxicity in CCK-8 assays, indicating a favorable preliminary safety profile. These results highlight the potential of GelMA/PCL/1.0 wt% GO scaffolds as a promising platform for advanced nerve guidance conduits; however, further validation using primary neurons and in vivo models is required. Full article
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14 pages, 799 KB  
Review
Stem Cell-Delivered Cytosine Deaminase/5-Fluorocytosine and TRAIL Gene Therapy for Castration-Resistant Prostate Cancer: Translational Synthesis and First-in-Human Trial Concept
by Jae Heon Kim, Miho Song, Kisoo Lee, Sang Hun Lee and Yun Seob Song
Int. J. Mol. Sci. 2026, 27(15), 6870; https://doi.org/10.3390/ijms27156870 - 31 Jul 2026
Viewed by 394
Abstract
Castration-resistant prostate cancer (CRPC) is characterised by persistent androgen receptor (AR)-axis activity, therapy-driven resistance, and limited durability of available systemic treatments. Tumour-tropic mesenchymal stem/stromal cells (MSCs), including adipose-derived MSCs (ADSCs), have emerged as promising vehicles for targeted gene therapeutics. This review synthesises our [...] Read more.
Castration-resistant prostate cancer (CRPC) is characterised by persistent androgen receptor (AR)-axis activity, therapy-driven resistance, and limited durability of available systemic treatments. Tumour-tropic mesenchymal stem/stromal cells (MSCs), including adipose-derived MSCs (ADSCs), have emerged as promising vehicles for targeted gene therapeutics. This review synthesises our three experimental studies examining stem cell-delivered gene-directed enzyme prodrug therapy (GDEPT) using cytosine deaminase (CD)/5-fluorocytosine (5-FC) and secreted TRAIL in CRPC xenograft models. We performed a comparative analysis of three studies in which hTERT-immortalised human ADSCs were engineered via lentiviral vectors to deliver CD alone, secreted TRAIL alone, or CD+TRAIL in combination, and were administered by intracardiac injection into male nude mice bearing PC3 xenografts. In vitro conversion efficiency, cell viability, apoptosis markers, and in vivo tumour volume endpoints were compared across studies. All three therapeutic platforms demonstrated measurable tumour growth inhibition relative to controls. The CD+TRAIL combination achieved the greatest in vivo efficacy (tumours approximately 26% of control at day 14), compared with CD alone (approximately 71%) or TRAIL paired with irinotecan. Enzymatic conversion of 5-FC to 5-FU exceeded 93% in conditioned medium. Primary translational risks include thrombotic events associated with systemic MSC dosing, tumourigenicity and genotoxicity of hTERT-immortalised, integrating-vector–engineered cells, immunogenicity of xenogeneic CD enzyme, and systemic 5-fluorouracil leakage from flucytosine metabolism. Stem cell-delivered CD/5-FC and TRAIL constitutes a biologically rational, modular strategy for local cytotoxicity and resistance circumvention in CRPC. Successful clinical translation will require resolution of delivery-route feasibility, thrombosis risk mitigation, and a rigorous investigational new drug (IND)-enabling safety package. Full article
(This article belongs to the Special Issue Prostate Cancer: Molecular Mechanisms and Targeting)
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29 pages, 6013 KB  
Article
Sub-Saharan African Prostate Cancer Patient-Derived Cell Lines and High-Throughput Drug Screening: Addressing Ancestry Underrepresentation in Oncobiology Research
by Carla S. Dos Santos, Ana C. Magalhães, Veronica Fernandes, António Pombinho, Lurdes Torres, Margarida André, Adelaide Sousa, Pedro Sequeira, Daniel Pinto, Cláudia Pereira, Paulo M. Costa, Lúcio Lara Santos and Luisa Pereira
Cancers 2026, 18(15), 2452; https://doi.org/10.3390/cancers18152452 - 30 Jul 2026
Viewed by 393
Abstract
Background/Objectives: Prostate cancer (PC) exhibits marked disparities in incidence and mortality across ethnicities, with men of Sub-Saharan African (SSA) ancestry experiencing 1.7 and 2.0 times higher values, respectively, than European men (EUR). However, SSA preclinical models remain scarce (just one commercial cell [...] Read more.
Background/Objectives: Prostate cancer (PC) exhibits marked disparities in incidence and mortality across ethnicities, with men of Sub-Saharan African (SSA) ancestry experiencing 1.7 and 2.0 times higher values, respectively, than European men (EUR). However, SSA preclinical models remain scarce (just one commercial cell line). In this study, we established and characterized a novel panel of PC cell lines derived from SSA patients using conditional reprogramming (CR), a method that enables efficient propagation of primary cells while maintaining their genotypic and phenotypic features. Methods: CR was applied to five SSA-PC samples, and successfully propagated samples were authenticated by STR and ~1 million SNP profiling, and extensively characterized for proliferative capacity, migratory behaviour, karyotyping and epithelial and prostate tumour lineage markers. To explore drug response profiles, a high-throughput screen (HTS) of 1280 clinically annotated compounds was conducted. Results: Three SSA-PC cell lines were successfully established and authenticated, and five potential drug hits were validated. A new finding was the reduced sensitivity of SSA-derived models (9.0 times difference compared to commercial EUR PC cell lines) to camptothecin, a TOP1 inhibitor, while being equally sensitive to epirubicin hydrochloride, a TOP2 inhibitor. The cardiac glycoside digoxin, anthelmintic pyrvinium pamoate and antirheumatic agent auranofin were also efficient drugs in the in vitro testing. Conclusions: These results support the relevance of SSA-derived PC models for preclinical drug screening and highlight the value of including ancestry-diverse models in oncobiology research. Full article
(This article belongs to the Section Molecular Cancer Biology)
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28 pages, 14935 KB  
Article
Integrated Chemical Profiling and Network Pharmacology Establish a Quality Evaluation Framework for the Four Medicinal Parts of Wolfiporia extensa (Peck) Ginns
by Shun-Xin Deng, Lih-Geeng Chen, Shih-Yi Hsiung, Vinh Tuyen T. Le, Chia-Jung Lee, Yves S. Y. Hsieh and Ching-Chiung Wang
Life 2026, 16(8), 1241; https://doi.org/10.3390/life16081241 - 27 Jul 2026
Viewed by 323
Abstract
Wolfiporia extensa (Peck) Ginns (WE) is a fungus widely used in Traditional Chinese Medicine. Its four medicinal parts, Poria (WP), Rubra Poria (RP), Poriae Cutis (PC), and Poria Cum Pini Radix (PPR), are prescribed for distinct therapeutic purposes; however, their quality standards and [...] Read more.
Wolfiporia extensa (Peck) Ginns (WE) is a fungus widely used in Traditional Chinese Medicine. Its four medicinal parts, Poria (WP), Rubra Poria (RP), Poriae Cutis (PC), and Poria Cum Pini Radix (PPR), are prescribed for distinct therapeutic purposes; however, their quality standards and pharmacological differences remain unclear. This study established reliable quality markers and compared the neuroprotective activities of four medicinal parts of WE. Seven triterpenoids were quantified using validated high-performance liquid chromatography (HPLC) assays, while monosaccharide profiles were analyzed using 1-phenyl-3-methyl-5-pyrazolone-HPLC. The International Commission on Illumination L*a*b* colorimetry and chemometric models were used for authentication. The neuroprotective effects of aqueous extracts were assessed in SH-SY5Y, BV-2, and HOG cell models. Network pharmacology was used to predict compound–target pathway relationships. The content of poricoic acid A (PAA) was the highest in PC; the content of pachymic acid (PA) was the highest in RP; whereas dehydrotumulosic acid (DTUA) was enriched in WP. WP demonstrated the highest mannose and galactose content. The water extract of WP reduced H2O2-induced cytotoxicity in SH-SY5Y cells, whereas the PC extract alleviated L-α-lysophosphatidylcholine-induced injury in human oligodendroglioma cells. Network analysis identified PA, PAA, and poricoic acid B (PAB) as candidate bioactive compounds involved in neuroprotective effects. The PA/PAB ratios of ≥10, 1–9, and ≤1 were used to identify WP, RP, and PC, respectively. L* values of >80, 55–79, and <55 effectively discriminated WP, RP, and PC, respectively. This integrative study identified chemical and functional quality markers and demonstrated distinct neuroprotective profiles in different parts of WE, supporting their standardized and rational application in traditional medicine and nutraceuticals. Full article
(This article belongs to the Section Pharmaceutical Science)
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19 pages, 3565 KB  
Article
Resveratrol Modulates Phosphatidylcholine Metabolism-Related Enzymes and Enhances Chemosensitivity in Colorectal Cancer Models
by Aurélie Mialhe, Elodie Mammar, Aline Mathey, Virginie Aires and Dominique Delmas
Int. J. Mol. Sci. 2026, 27(15), 6691; https://doi.org/10.3390/ijms27156691 - 27 Jul 2026
Viewed by 233
Abstract
Colorectal cancer (CRC) remains a major cause of cancer-related mortality worldwide, largely due to the emergence of chemoresistance driven by metabolic adaptations. Among these alterations, lipid metabolic reprogramming has emerged as a critical determinant of tumor progression and therapeutic response. In particular, dysregulation [...] Read more.
Colorectal cancer (CRC) remains a major cause of cancer-related mortality worldwide, largely due to the emergence of chemoresistance driven by metabolic adaptations. Among these alterations, lipid metabolic reprogramming has emerged as a critical determinant of tumor progression and therapeutic response. In particular, dysregulation of enzymes involved in phosphatidylcholine (PC) synthesis and remodeling, through the Kennedy pathway and the Lands cycle, has been associated with therapeutic resistance. Lysophosphatidylcholine acyltransferase 2 (LPCAT2), a key enzyme involved in PC remodeling, notably promotes lipid droplets (LD) accumulation in CRC cells and contributes to chemoresistance. In this context, natural compounds capable of modulating PC metabolism, such as the polyphenol resveratrol (RSV), may represent a relevant strategy to improve sensitivity to chemotherapies in chemoresistant colon tumor cells. In this study, RSV induced apoptosis and significantly reduced the proliferation of intrinsically resistant HT29 cells and SW620 cells engineered to overexpress LPCAT2. RSV also decreased the expression of key enzymes involved in the Kennedy pathway in chemoresistant CRC cell lines. These changes were accompanied by distinct time-dependent patterns of lipid droplet accumulation in the two cellular models. In addition, drug combination studies showed that RSV enhanced the response to 5-fluorouracil (5-FU), oxaliplatin (OXA) and the FOX regimen (5-FU + OXA, 1:1 ratio) with synergistic interactions for several dose combinations, together with favorable dose-reduction indices. Collectively, these in vitro findings indicate that RSV modulates PC-metabolism-related proteins and enhances chemotherapy sensitivity in resistant CRC models. Overall, our results identify RSV as a promising therapeutic strategy to target metabolic vulnerabilities associated with PC metabolism and overcome chemoresistance in CRC. Full article
(This article belongs to the Special Issue Lipid Metabolism in Aging and Diseases: From Mechanisms to Therapy)
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12 pages, 1155 KB  
Article
Selective CB2 Agonist JWH-133 Suppresses Viability and Migration-Related Responses in Prostate Cancer Cells
by Seda Sabah Özcan, Rehime Yapar, İsmail Değerli, Levent Elmas, Mehmet Korkmaz and Murat Çakır
Pharmaceuticals 2026, 19(7), 1114; https://doi.org/10.3390/ph19071114 - 19 Jul 2026
Viewed by 443
Abstract
Background/Objectives: Cannabinoid receptor type 2 (CB2) agonists have attracted attention because of their potential effects on tumor-related cellular processes in different cancer models. In the present study, we investigated the effects of the selective CB2 agonist JWH-133 on prostate [...] Read more.
Background/Objectives: Cannabinoid receptor type 2 (CB2) agonists have attracted attention because of their potential effects on tumor-related cellular processes in different cancer models. In the present study, we investigated the effects of the selective CB2 agonist JWH-133 on prostate cancer cell lines (LNCaP, DU-145, and PC3). Methods: Cell viability was evaluated using the MTT assay, while colony-forming capacity and migration-related responses were assessed by colony formation and wound-healing assays, respectively. In addition, the expression levels of selected cell-cycle- and apoptosis-related genes were analyzed by quantitative real-time PCR. Results: JWH-133 reduced cell viability in a time- and concentration-dependent manner, although the magnitude of this effect differed among prostate cancer cell lines. The compound also reduced colony formation in PC3 and LNCaP cells and decreased wound closure in PC3 cells under the experimental conditions used. Furthermore, JWH-133 altered the expression of several cell-cycle- and apoptosis-related genes in DU-145 and PC3 cells. Conclusions: Overall, these findings suggest that JWH-133 modulates multiple cellular responses in prostate cancer cells in a cell-line-dependent manner. However, additional mechanistic studies are required to clarify the molecular pathways underlying these effects. Full article
(This article belongs to the Section Biopharmaceuticals)
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