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Review Article Open Access
Zhiwei Zheng, He Xu, Dandan Yang, Jing Yin, Kexin Si, Hao Ai, Ying Liu
Published online October 3, 2025
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Oncology Advances. doi:10.14218/OnA.2025.00013
Abstract
Chimeric antigen receptor (CAR)-T cell therapy faces significant challenges in treating solid tumors, including immune evasion, suppressive tumor microenvironments, and on-target/off-tumor [...] Read more.

Chimeric antigen receptor (CAR)-T cell therapy faces significant challenges in treating solid tumors, including immune evasion, suppressive tumor microenvironments, and on-target/off-tumor toxicity, which limit its clinical efficacy. Although it has revolutionized treatment for hematological malignancies, these obstacles hinder its broader application in solid tumors. Nanotechnology offers innovative strategies to address these limitations through enhanced delivery, localization, and control. This review summarizes recent advances in nanotechnology-assisted CAR-T cell therapies for gynecologic cancers, with a particular focus on messenger RNA (mRNA)-based delivery systems, lipid nanoparticles, hydrogels, and external activation techniques such as photothermal and acoustogenetic modulation. The integration of nanotechnology, especially mRNA-based delivery systems, holds transformative potential for overcoming these barriers. mRNA enables transient, non-integrating expression of CARs, meaning the genetic modifications are temporary. This improves safety and allows flexible control over treatment intensity, while rational sequence optimization (e.g., codon usage, guanine-cytosine content, secondary structure) enhances mRNA stability and protein translation efficiency. Lipid nanoparticles, the leading delivery platform, can be engineered for cell-type specificity and tissue targeting through modulation of their components and surface functionalization. Recent innovations, including siloxane-modified lipid nanoparticles, injectable hydrogels, and photothermal or acoustogenetic activation strategies, enable precise spatiotemporal control of CAR-T cell function in vivo. In ovarian cancer, preclinical studies targeting nfP2X7 and employing multifunctional nanoparticles have demonstrated synergistic efficacy and tumor-specific delivery. This review highlights how nanotechnology platforms can be integrated with CAR-T cell therapies to enhance safety, precision, and therapeutic outcomes in ovarian cancer.

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Original Article Open Access
Trevor R. Norman, Caroline McGrath
Published online September 30, 2025
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00033
Abstract
Preclinical studies of the serotonin 2A (5-HT2A) antagonist deramciclane suggested an anxiolytic profile, which has not been unequivocally established in the clinic. The same receptor [...] Read more.

Preclinical studies of the serotonin 2A (5-HT2A) antagonist deramciclane suggested an anxiolytic profile, which has not been unequivocally established in the clinic. The same receptor profile also indicated that the compound may exhibit antidepressant potential. However, evidence for these effects remains inconclusive. The present study examined the effect of the drug in two preclinical tests with predictive validity for antidepressant activity.

The antidepressant-like activity of deramciclane was assessed in male Sprague-Dawley rats by measuring immobility time in the forced swim test (doses: 1, 5 mg/kg) and ambulation scores in the bilateral olfactory bulbectomized (doses: 5, 10 mg/kg) rat model. In both tests, the clinically effective antidepressant imipramine served as the control condition.

In the forced swim test, there was a statistically significant effect of treatment on immobility time (F2,34 = 5.77; p < 0.01; analysis of variance), which was attributable to the effect of the 5 mg/kg dose (p < 0.01; Bonferroni post-hoc test). Deramciclane at 1 mg/kg was not significantly different from vehicle-treated animals. By contrast, neither dose of deramciclane (5 mg/kg or 10 mg/kg) reversed the hyperactivity of olfactory bulbectomized rats, whereas imipramine was active in both tests.

Deramciclane demonstrates contradictory evidence for antidepressant-like activity in two validated pharmacological tools that identify such potential. The agent is clearly active in the forced swim test but not in the bulbectomized rat model. Further evaluation of the antidepressant-like potential of deramciclane in pharmacological models with predictive validity is warranted, and a more detailed examination of the dose-response relationship may be informative.

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Original Article Open Access
Roa’a Haraka, Raghad Alghamdi, Orjwan Sami Mattar, Arwa Alharthi, Thekra Algasim, Sherooq Haraka, Mohammed Shammas, Muazzam Sheriff Maqbul
Published online November 4, 2025
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00034
Abstract
Clove essential oil (CEO) derived from Syzygium aromaticum and miswak (Salvadora persica) contains bioactive compounds with antimicrobial properties. Due to the growing interest [...] Read more.

Clove essential oil (CEO) derived from Syzygium aromaticum and miswak (Salvadora persica) contains bioactive compounds with antimicrobial properties. Due to the growing interest in alternatives to conventional antibiotics, this study aimed to evaluate the in vitro antimicrobial efficacy of CEO, miswak, and their combination against key peri-implantitis pathogens.

The antimicrobial activities of CEO, miswak, and their combinations were tested against Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia. Disc diffusion and serial dilution methods were used to measure the inhibition zones and minimum inhibitory concentrations, respectively. Doxycycline served as a standard antibiotic for comparison, while ethanol was used as a negative control. Data were analyzed using one-way analysis of variance and Tukey’s honestly significant difference test, with significance set at α = 0.05.

CEO exhibited inhibition zones of 10–16 mm, comparable to that of doxycycline (13–16 mm), whereas miswak (6–13 mm vs. 1–14 mm) and the CEO–miswak combination (8–14 mm vs. 0–14 mm) showed lower activity. Mean minimum inhibitory concentration values were lowest for doxycycline (1.73 ± 0.46 µg/mL), followed by CEO (2.37 ± 0.24 µg/mL) and CEO–miswak combination (2.92 ± 0.12 µg/mL). Statistical analysis showed that the CEO–miswak combination was less effective than CEO (p = 0.0326) and doxycycline (p = 0.0001), but not different from miswak (p = 0.9836). CEO showed slightly greater activity than miswak (p = 0.0605).

Among the natural extracts tested, CEO exhibited superior antimicrobial efficacy, whereas miswak was less effective. The combination of CEO with miswak did not enhance antimicrobial efficacy, suggesting antagonistic interactions between their bioactive compounds.

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Research Letter Open Access
Niki Shrestha, Akram Shalaby, Hannah H. Chen, Navid Sadri, Min Cui
Published online October 14, 2025
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Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00026
Original Article Open Access
Susu Jiang, Yuling Su, Yuqi Hong, Haiyan Wu, Wenli Zhang, Jing He, Chunlei Zhou, Zhenjian Zhuo
Published online September 30, 2025
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Cancer Screening and Prevention. doi:10.14218/CSP.2025.00019
Abstract
5-methylcytosine RNA modification is a key regulator of neuroblastoma oncogenesis and differentiation. NSUN6, a 5-methylcytosine-specific messenger RNA methyltransferase, modulates [...] Read more.

5-methylcytosine RNA modification is a key regulator of neuroblastoma oncogenesis and differentiation. NSUN6, a 5-methylcytosine-specific messenger RNA methyltransferase, modulates messenger RNA methyltransferase activity and translation termination. Yet, its potential link to neuroblastoma risk has not been previously reported. The present study aimed to reveal the relationship between NSUN6 gene polymorphisms and the risk of neuroblastoma in children from Jiangsu province.

In this case-control study, we investigated three NSUN6 gene polymorphisms (rs3740102 A>C, rs12780826 T>A, and rs61842187 G>C) in 402 neuroblastoma cases and 473 controls, all of whom were children from Nanjing City, Jiangsu Province, China. DNA from these subjects was assessed using the TaqMan method. Multivariate logistic regression analysis was employed to examine the association between NSUN6 gene polymorphisms and neuroblastoma risk. Additionally, the Genotype-Tissue Expression database was utilized to elucidate the impact of these polymorphisms on NSUN6 and nearby gene expression. Kaplan-Meier analysis and the non-parametric test were conducted on the R2 platform to assess the relationship between gene expression, prognosis, and neuroblastoma risk.

Carriage of two to three protective genotypes (rs3740102 AA/AC, rs12780826 TT/TA, rs61842187 CC) was significantly associated with a lower risk of neuroblastoma (adjusted odds ratio = 0.41, 95% confidence interval = 0.23–0.73, P = 0.002), with consistent results across all subgroups. Expression quantitative trait locus analysis showed these single-nucleotide polymorphisms may upregulate the expression of NSUN6 and CACNB2. Furthermore, higher NSUN6 and CACNB2 expression was correlated with a potentially lower risk of neuroblastoma, improved overall survival (NSUN6: P = 2.54e-03; CACNB2: P = 6.35e-06) and event-free survival (NSUN6: P = 7.90e-04; CACNB2: P = 4.64e-06), as well as a lower likelihood of MYCN amplification.

NSUN6 rs3740102 AA/AC, rs12780826 TT/TA, and rs61842187 CC genotypes may be associated with a better prognosis of neuroblastoma. This association may be related to the potential upregulation of NSUN6 gene expression and a lower likelihood of MYCN amplification.

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Original Article Open Access
Pedro Ribeiro, João Alexandre Lobo Marques, Marconi Pereira Brandão, Octávio Barbosa Neto, Camila Ferreira Leite, Pedro Miguel Rodrigues
Published online November 6, 2025
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Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00037
Abstract
Cardiovascular diseases account for approximately 80% of all deaths caused by known medical conditions, making them the leading cause of mortality worldwide. The present study investigates [...] Read more.

Cardiovascular diseases account for approximately 80% of all deaths caused by known medical conditions, making them the leading cause of mortality worldwide. The present study investigates the use of electrocardiogram (ECG) non-linear features and different topological medical features (heart rate, anthropometry, blood, glucose, and lipid profile, and heart rate variability) to discriminate between different Framingham Cardiovascular Risk Scale status groups in adult obesity using machine learning.

We conducted a cross-sectional study between November 2023 and May 2024 in Fortaleza, Ceará, Brazil. Based on the Framingham Cardiovascular Risk Scale, patients were categorized into three cardiovascular risk groups: Low (22 participants), Moderate (14 participants), and High (17 participants). From ECG signals at two different positions (ECG_Down and ECG_UP), 27 non-linear features were extracted using multi-band analysis. Additionally, 42 medical features provided by physicians were included. From a pool of 19 machine learning classifiers, models were trained and tested within a nested leave-one-out cross-validation procedure using information solely from ECG, solely from medical features, and combining both (multimodal), respectively, to distinguish between Low vs. Moderate, Low vs. High, Moderate vs. High, and All vs. All.

The multimodal model presented the best results for every comparison group, reaching (1) 88.89% Accuracy and 0.8831 area under the curve (AUC) for Low vs. Moderate; (2) 97.44% Accuracy and 0.9706 AUC for Low vs. High; (3) 93.55% Accuracy and an AUC of 0.9412 for Moderate vs. High; (4) 86.79% Accuracy and 0.9346 AUC for All vs. All.

The multimodal model outperformed single-source models in cardiovascular risk classification. ECG-derived non-linear features, especially from ECG_Down, were key drivers, with medical features adding complementary value. The results support its potential use in clinical triage and diagnosis.

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Research Letter Open Access
Elisa Herraez, Maria J. Monte, Marta Alonso-Peña, Jesus Prieto, Luis Bujanda, Milagros Muñoz-Chimeno, Ana Avellon, Jose J.G. Marin
Published online October 17, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00329
Editorial Open Access
Mina Sarofim
Published online September 30, 2025
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Cancer Screening and Prevention. doi:10.14218/CSP.2025.00017
Editorial Open Access
Jia Shen, Lihua Ren, Hong Chen
Published online September 30, 2025
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Cancer Screening and Prevention. doi:10.14218/CSP.2025.00020
Original Article Open Access
Pei Wang, Xuerui Yang, Danfeng Li, Bing Li, Yali Wan, Ye Yuan, Gefen Yue, Yuxin Zhan
Published online November 11, 2025
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Neurosurgical Subspecialties. doi:10.14218/NSSS.2025.00018
Abstract
Stroke patients have a high incidence of venous thromboembolism (VTE). Improving the prevention and control rates of VTE in stroke patients can enhance their quality of life. The [...] Read more.

Stroke patients have a high incidence of venous thromboembolism (VTE). Improving the prevention and control rates of VTE in stroke patients can enhance their quality of life. The aim of this study was to analyze the effect of 4R crisis management combined with the health belief model in the prevention and control of VTE in stroke patients.

A randomized controlled trial was conducted on 86 stroke patients in the neurosurgery department of a tertiary hospital in Wuhan. The control group was treated with the routine VTE prevention and control strategy, while the experimental group was treated with 4R crisis management combined with the health belief model. The primary outcome measures were the incidence rates of deep vein thrombosis and pulmonary thromboembolism, while the secondary outcome measures were the Short Form Health Belief Model Scale score, medical quality evaluation, and stroke patients’ health behavior scale score. The statistical analysis methods included t-tests and non-parametric tests.

After the intervention, the incidence rate of deep vein thrombosis in the control group was 14.6% (6/41), while in the experimental group it was 2.4% (1/41). The difference was statistically significant (χ2 = 3.905, P = 0.048). The incidence rates of pulmonary thromboembolism in both groups were 0%. The scores of all dimensions of the Short Form Health Belief Model Scale in the experimental group were higher than those in the control group, and the difference was statistically significant (P < 0.05, P < 0.01). The medical quality for each item showed that the experimental group performed better than the control group, with the difference being statistically significant (P < 0.05, P < 0.01). The scores on the stroke patients’ health behavior scale in the experimental group were higher than in the control group, except for responsibility, tobacco, and alcohol (P < 0.01).

The application of 4R crisis management combined with the health belief model can effectively improve the health beliefs and health behaviors of stroke patients to prevent VTE, thereby reducing the incidence of VTE.

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