Therapeutic Tool Research Articles

High-throughput screen identifies MAS9 as a novel inhibitor of the C-type lectin receptor-2 (CLEC-2)-podoplanin interaction.

The C-type lectin-like receptor-2 (CLEC-2) is a platelet receptor for the endogenous ligand podoplanin. This interaction contributes to several (patho)physiological processes, such as lymphangiogenesis, preservation of blood and lymphatic vessel integrity organ development, and tumour metastasis. Activation of CLEC-2 leads to the phosphorylation of its cytoplasmic hemITAM domain and initiates a signalling cascade involving the kinase Syk. The aim of this study was to identify and characterise a novel small molecule inhibitor of CLEC-2. An AlphaScreen-based high-throughput screening was used to identify a small molecule inhibitor of the CLEC-2-podoplanin interaction. Binding site interactions were assessed using in silico modelling. Functional assays, including light transmission aggregometry, platelet spreading and phosphorylation assays, were used to evaluate the effect of a small molecule on CLEC-2-mediated platelet activation. A total of 18,476 small molecules were screened resulting in 14 candidates. Following secondary screening, one novel small molecule, MAS9, was taken forward for further characterisation. The binding sites of MAS9 to CLEC-2 were predicted to share binding sites with the CLEC-2 ligands podoplanin and rhodocytin. MAS9 inhibited CLEC-2-mediated platelet aggregation, spreading and signalling. MAS9 also resulted in inhibited fibrinogen binding. MAS9 inhibits CLEC-2-mediated aggregation, platelet spreading and signalling, showing selectivity of CLEC-2 inhibition over GPVI. This study paves the way for future preclinical assays to test the potential of MAS9 as a novel therapeutic tool to treat pathologies such as thromboinflammation and cancer.

Development of Comprehensive Screening and Assessment Assays for Small-Molecule Ligands of MALAT1 lncRNA.

RNA targeting represents an original and promising approach to the discovery of new therapeutic tools against numerous diseases. The majority of intracellular RNAs are noncoding RNAs that play key regulatory functions in many physiological processes. Among these RNAs, long noncoding RNAs (lncRNAs) constitute the largest class of noncoding transcripts and have been shown to play important functional roles in development and disease processes. In this work, we developed a set of biochemical assays for the discovery of efficient small-molecule lncRNA ligands selective for their target, focusing on MALAT1 lncRNA. The latter bears a particular structure including a triple helical region important for its function, and it has been linked to cancer cells' proliferation. However, its role in cancer still needs to be completely elucidated. The application of these assays to an original library of RNA binders allowed for the discovery of unprecedented ligands of the MALAT1 triple helix able to inhibit and destabilize the triple helical MALAT1 structure. The set of screening and validation assays developed could find application in the discovery of new MALAT1 binders, and the new chemical scaffolds discovered in this study represent promising chemical probes for the study of the biological role of MALAT1 in disease.

Anti-inflammatory activity of magnetic fields emitted by graphene devices on cultured human cells

BackgroundInflammation plays a key role in various diseases such as pancreatitis, cancer, and rheumatoid arthritis. Acute inflammation involves processes like vasodilation, increased vascular permeability, and leukocyte accumulation, which lead to cellular damage due to reactive oxygen species (ROS). Low-frequency electromagnetic fields (ELF-EMFs) have shown potential in reducing oxidative stress and inflammation. This study assesses the effectiveness of a new wearable device containing graphene quantum dots in reducing inflammation and oxidative stress in Jurkat T cells stimulated by lipopolysaccharide (LPS). The device is evaluated for its impact on ROS production and inflammation.ResultsThe results show that the device significantly lowers ROS levels and reduces the inflammatory response by decreasing pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Additionally, the device inhibits LPS-induced iNOS and COX-2 activity and modulates NF-κB signaling, indicating its potential as a therapeutic tool for managing inflammation and oxidative stress.ConclusionThese findings highlight the device’s ability to combat inflammation, offering a non-invasive and effective approach for inflammatory diseases.

Abstract 2148: HDAC6 inhibitors modulate macrophage functional activity in the post-radiotherapy tumor microenvironment

Abstract Introduction: In recent decades, radiation therapy (RT) has been a significant therapeutic tool for treating multiple cancer types. Primarily, radiation-induced immunogenic tumor cell death re-modulates the tumor microenvironment (TME) with the potential to enhance the efficacy of immunotherapies. Tumor-associated macrophages (TAMs) play a critical role in the anti-tumor innate immune response. However, post-RT, the phenotype of TAMs can easily convert from the pro-inflammatory M1-like to the immunosuppressive and tumor-promoting M2-like due to their plasticity. M2-like macrophages cause relapse and metastasis of the tumor. Therefore, reprogramming TAMs is critical. Our lab has reported that targeting Histone Deacetylase 6 (HDAC6) in macrophages can disrupt their phenotype shifting from M1-like to M2-like in TME. Methods: We demonstrated the suppressive effect of HDAC6 inhibitors (HDAC6i) on M2-like macrophage phenotype markers by flow cytometry and qRT-PCR. Furthermore, in-vitro assays were performed, including trans-well migration assays, phagocytosis assays, and in-vivo syngeneic tumor models against different tumor cell types, including SM1 murine melanoma, 4T1 breast cancer, and TRAMP-C2 prostate cancer. Results: The trans-well-based migration assay indicated an increment in M2-like macrophage migration to irradiated cancer cells compared to M1-like macrophages. This increment was suppressed when culturing M2 macrophages with HDAC6i. Furthermore, the co-culture assay between macrophages and cancer cells indicated that M1 macrophages showed a higher phagocytosis rate when co-culture with irradiated cells and HDAC6i treatment increased tumor cell phagocytosis. Meanwhile, an in-vivo study based on the 4T1 and SM1 tumor models model suggested that RT combined with HDAC6i treatment has better efficacy than the monotherapy treatment arms due to increased M1/M2 macrophage ratio. These results demonstrate that targeting macrophages with HDAC6is could enhance the overall therapeutic outcome of radiation therapy. Citation Format: Xintang Li, Satish Noonepalle, Karen Tan, Sonia Sebaoui, Manasa Suresh, Nithya Gajendran, Marie Durr, David Quiceno-Torres, Bryan Weselman, Vidhi Sharma, Abishek Sehgal, Scott Grindrod, Anatoly Dritschilo, Alejandro Villagra. HDAC6 inhibitors modulate macrophage functional activity in the post-radiotherapy tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2148.

Abstract 5842: A novel formulated neoantigen DNA vaccine with promising anticancer efficacy in B16F10 mouse melanoma model

Abstract Cancer vaccine approaches targeting neoantigens are gaining credence due to their specificity for tumors while sparing healthy tissues. Cancer vaccines based on DNA technology are attractive anti-cancer therapeutic tools due to their ability to elicit an effector T-cell-based immune responses. We report the development of a novel DNA-based cancer vaccine that relies on the delivery of a plasmid DNA vector encompassing immune epitopes of multiple neoantigens delivered with a novel synthetic DNA delivery system with the aim to elicit a broader immune response against cancer. The formulated vaccine was also investigated in combination with different adjuvants to maximize the anti-cancer responses. The vaccine vector encoding the immunogenic epitopes of multiple melanoma neoantigens and flanked by signal peptide at N-terminus and an MHC-targeted domain at the C-terminus end was formulated with a functionalized novel synthetic polymer with or without the adjuvants Poly I:C, diABZI, a STING agonist, or a mouse IL-12 plasmid. Mice were implanted subcutaneously with 0.5 x 106 B16F10 tumor cells on Day 0 and vaccinated intramuscularly with the DNA formulations on Day 2, 9, 16 and 23, and monitored for tumor growth and survival . For cellular responses, mice were injected intramuscularly with the DNA formulations on Day 0, 21, 42 and sacrificed 7 days later for cellular immune response by ELISPOT assay. Vaccination with formulated DNA alone yielded a significant inhibition (60%, p<0.01) of tumor growth and improved survival. Addition of Poly I:C, diABZI, or IL-12 plasmid further augmented the tumor inhibition to 90%(p<0.0001), 94%(p<0.0001), and 88% (p<0.0001), respectively, and improved the survival outcome. All animals in the adjuvant groups also lived longer. The anti-tumor efficacy results are supported by the onset of robust T-cell responses in all treatment groups supporting the involvement of immune activation in the action of this novel DNA vaccine that does not require a virus or device and can be manufactured rapidly with a simple and cost-effective manufacturing process critical for the viability of cancer vaccines. Citation Format: Kempaiah Rayavara, Subeena Sood, Majed Matar, Jessica Kim, John Henderson, Jeff Sparks, Meredyth Kinsella, Olivia Signer, Joseph Rogers, Chelsey Bellmon, Khursheed Anwer. A novel formulated neoantigen DNA vaccine with promising anticancer efficacy in B16F10 mouse melanoma model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5842.

MicroRNA in cancer therapy: breakthroughs and challenges in early clinical applications.

MicroRNAs (miRNAs) have emerged as pivotal regulators in cancer biology, influencing tumorigenesis, progression, and resistance to therapy. Their ability to modulate multiple oncogenic and tumor-suppressive pathways positions them as promising therapeutic tools or targets. This review examines the dual role of miRNAs in solid and hematological malignancies, starting from their dysregulation in various cancer types. Therapeutic approaches, including miRNA replacement and inhibition strategies, are discussed alongside innovative delivery systems such as lipid nanoparticles and exosomes. Despite their transformative potential, challenges persist, including off-target effects, immune activation, and delivery inefficiencies. Recent clinical trials demonstrate both progress and hurdles, underscoring the need for advanced strategies to optimize specificity and minimize toxicity. This review provides an updated comprehensive overview of the current landscape of miRNA-based therapies under early clinical investigation and explores future directions for integrating these approaches into precision oncology.

Abstract 2585: GABA shunt pathway promotes peri-synaptic brain metastasis by hijacking synaptic signaling

Abstract Metastatic brain tumors are the most common intracranial neoplasms in adults. Among all subtypes of breast cancer, triple-negative breast cancer (TNBC) has a significantly poorer prognosis compared to other subtypes. Pre-menopause and estrogen replacement therapy after menopause have been shown to increase the risk of brain metastases in TNBC patients. Estrogen blockade using tamoxifen demonstrates some efficacy in TNBC, suggesting that estrogen promotes brain metastases by modulating the tumor microenvironment in estrogen receptor (ER)-negative tumors. Neurons, as highly specialized cells responsible for cell-to-cell signal transmission, are among the most critical and abundant cell types in the brain. However, the role of tumor-associated neurons and their contributions to TNBC remain poorly understood. We hypothesize that estrogen promotes brain metastasis in hormone receptor-negative breast cancer by increasing the release of gamma-aminobutyric acid (GABA), which serves as a metabolic substrate to fuel tumor cell growth. We further hypothesize that blocking GABA transporter function will suppress brain metastases in hormone receptor-negative breast cancer. Our findings show that pre-menopausal TNBC patients exhibit higher synaptic formation and increased expression of GABA transporters in brain metastases, suggesting that neurons may contribute to tumor growth. To investigate the effect of estrogen on brain metastasis in ER-negative breast cancer aCnd to understand how estrogen depletion modulates metastatic growth in the brain, we performed bilateral ovariectomy in female mice and intracardially implanted luciferase-labeled human ER-negative brain metastatic breast cancer cells (231BrM). Our results demonstrate that estrogen increases synaptic formation and upregulates the expression of GABA and GABA transporter 1 (GAT1) in brain metastases more prominently than other neurotransmitter receptors. To examine the effect of GABA on tumor progression, 231BrM cells were treated with 0.5 mM GABA, mimicking physiological brain concentrations, or recombinant GABA. We found that GABA treatment upregulated GAT1 expression and enhanced colony formation and migration abilities, strongly suggesting that GABA promotes brain metastasis. Furthermore, treating 231BrM cells with conditioned medium (CM) obtained from GABAergic neurons exposed to estrogen led to increased tumor growth through activation of the GABA shunt pathway in tumor cells. Blocking GAT1 using CRISPR/Cas9 or a small-molecule GAT1 inhibitor effectively suppressed GABAergic neuron-induced tumor progression. Our results suggest that estrogen enhances GABA release from neurons, subsequently promoting activation of the GABA shunt pathway in tumor cells. This study highlights GAT1 inhibitors as promising therapeutic tools for treating TNBC patients with brain metastases. Citation Format: Shih-Ying Wu, Kerui Wu, Abhishek Tyagi, Ravindra Pramod Deshpande, Eleanor Cecile Smith, Jee Won Kim, Kounosuke Watabe. GABA shunt pathway promotes peri-synaptic brain metastasis by hijacking synaptic signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2585.

Immunomodulatory and cardio-protective effects of differentially originated multipotent mesenchymal stroma cells during polymicrobial sepsis in mice

PurposeSepsis is a life-threatening condition with cardiac complications being an independent predictor of poor outcome. Although their mechanisms have been widely investigated, therapeutic options remain limited. One promising therapeutic tool are mesenchymal stromal cells (MSCs). The aim of this study is to investigate the immunomodulatory effects of human MSCs from two different sources (bone marrow/BMMSC and adipose tissue/ASC) and to evaluate their cardioprotective potential.Methods60 adult male C57BL/6 mice were divided into sham, sepsis (cecal ligation puncture (CLP)) and two i.v. treatment groups CLP + human BMMSC and CLP + human ASC with 5 animals in each group. The observation periods were 8, 24 and 72 h. Left ventricular tissue was analyzed histologically, by qPCR (C3ar, C5ar1, Il-1b, Il-6, Il-10, Tlr2, Tlr4, Tnfa, and Nlrp3) and western blot. Cardiac damage markers troponin I and heart fatty acid binding protein (HFABP) were detected in serum by ELISA.ResultsTroponin I and HFABP were significantly increased in CLP group after 8 h compared to sham. In cardiac tissue the expression of C3ar, C5ar1, Il-1b, Il-6, Il-10, Tlr2, Tlr4, Tnfa and Nlrp3 inflammasome was upregulated up to 24h after CLP compared to sham. After BMMSC treatment, C3ar as well as C5ar, Tlr2 and Il-10 mRNA expression in left ventricle was downregulated compared to CLP, whereas ASC treatment was associated with the downregulation of Il-6 and Nlrp3.ConclusionsCLP-induced polymicrobial sepsis in mice was associated with cardiac damage and increased inflammation in left ventricular tissue. Therapeutic systemic application of human BMMSC and ASC ameliorated damage and inflammation in the heart.

The human phageome: niche-specific distribution of bacteriophages and their clinical implications.

Bacteriophages (phages) play a crucial role in shaping the composition and diversity of the human microbiome across various body niches. Recent advancements in high-throughput sequencing technologies have enabled comprehensive analysis of the human phageome in different body sites. This review comprehensively analyzes phage populations across major human body niches, examining their distribution and dynamics through recent metagenomic discoveries. We explore how phage-bacteria interactions within different body sites contribute to homeostasis and disease development. Emerging evidence demonstrates that phageome perturbations can serve as early indicators of various disorders, particularly in the gut microbiome. Understanding these complex microbial interactions offers promising opportunities for developing novel diagnostic markers and therapeutic approaches. However, the causal relationship between phages, bacteria, and disease development remains unclear. Further research is needed to elucidate the role of phages in human health and disease and to explore their potential as diagnostic or therapeutic tools. Understanding the intricate interactions between phages, bacteria, and the human host is crucial for unraveling the complexities of the human microbiome and its impact on health and disease.

A pilot study on the effect of video games on ASD children's mental health and behaviour and oral health management in Syria – 2023

This pilot study investigates the impact of video games on the mental health and behavior of children with autism spectrum disorder (ASD) in Syria. With the increasing prevalence of ASD and the growing popularity of video games, understanding the potential benefits and risks of gaming for children with ASD is crucial. The study explores whether video games can serve as a therapeutic tool or if they contribute to behavioral deterioration and addiction. A sample of 50 children aged 6 to 12 years, diagnosed with ASD according to ICD-11 criteria, participated in the study. Data were collected through structured questionnaires completed by parents, assessing gaming habits, behavioural changes, and the level of video game addiction using the Internet Gaming Disorder Scale - Modified Short Form (IGDS9-SF). The study also evaluated the effects of replacing violent or repetitive games with more creative and interactive options, such as Minecraft and Super Mario Bros.Results indicated that 90% of the children preferred playing video games over other activities, with boys showing a higher preference for violence and fighting games. Approximately 54% of the children exhibited signs of video game addiction, while 14% were classified as fully addicted. During gameplay, 74% of the children displayed negative behaviors, such as increased aggression and reduced communication. However, after switching to more constructive games, significant improvements in communication, social interaction, and behavior control were observed.The study concludes that while video games offer potential benefits for children with ASD, including improved social skills, reduced anxiety, and enhanced problem-solving abilities, they also pose significant risks, particularly in terms of addiction and negative behavioral outcomes. The type of game played is a critical factor in determining the impact of gaming on children with ASD. A careful selection of games that promote creativity, cooperation, and cognitive development can help harness the positive aspects of gaming while mitigating its potential harms. This study highlights the need for further research into video game-based interventions tailored specifically for children with ASD, aiming to balance therapeutic benefits with the risks of excessive gaming.

Artificial Intelligence Applications in Pediatric Oncology Imaging: A Systematic Review of Diagnostic, Prognostic, and Therapeutic Evaluation Tools

Artificial Intelligence Applications in Pediatric Oncology Imaging: A Systematic Review of Diagnostic, Prognostic, and Therapeutic Evaluation Tools

Three-Dimensional Printing and Its Impact on the Diagnosis and Treatment of Neurodegenerative Disease

Neurodegenerative disorders include Alzheimer’s and Parkinson’s, both of which lead to progressive loss of neurons resulting in the severe loss of cognitive and motor functions. These diseases are among the heavy burdens on global healthcare systems largely because there is no cure, and current treatments apply almost entirely to controlling symptoms rather than disease progression. Recent advances in 3D printing and bioprinting technologies now open the way to overcome these challenges and form patient-specific models and therapeutical tools closely simulating the complex environment of the human brain. It then further illustrates how this technological integration with the aid of 3D printing, coupled with microfabrication and biosensing technologies, transforms drug-screening platforms as well as develops customization in medicine. For example, one can form highly intricate and multi-materially composed structures to better facilitate one’s study or test into some new therapeutic possibilities using methodologies of stereolithography and selective laser sintering. Moreover, 3D printing allows the creation of organ-on-a-chip models that simulate brain-like conditions, which may help identify specific biomarkers and evaluate new options of therapy. On the other hand, bioprinting methods based on neural cells combined with scaffolds mimicking native tissue dramatically transform regenerative medicine. New pathways in neural tissue development and implantable devices are now being brought forth, which can be tailored to the needs of individual patients. These advances bring not only greater precision in terms of the therapy that can be delivered but also 3D printing of implantable microelectrodes able to determine real-time biomarkers responsible for neurodegenerative diseases. Thus, this review highlights the robust impact that might be brought forth on the diagnosis and treatment of these neurodegenerative diseases via 3D printing technologies toward more effective management and personal solutions for healthcare.

Neurocomputational Mechanisms of Sense of Agency: Literature Review for Integrating Predictive Coding and Adaptive Control in Human-Machine Interfaces.

The sense of agency (SoA)-the subjective experience of controlling one's own actions and their consequences-is a fundamental aspect of human cognition, volition, and motor control. Understanding how the SoA arises and is disrupted in neuropsychiatric disorders has significant implications for human-machine interface (HMI) design for neurorehabilitation. Traditional cognitive models of agency often fail to capture its full complexity, especially in dynamic and uncertain environments. This review synthesizes computational models-particularly predictive coding, Bayesian inference, and optimal control theories-to provide a unified framework for understanding the SoA in both healthy and dysfunctional brains. It aims to demonstrate how these models can inform the design of adaptive HMIs and therapeutic tools by aligning with the brain's own inference and control mechanisms. I reviewed the foundational and contemporary literature on predictive coding, Kalman filtering, the Linear-Quadratic-Gaussian (LQG) control framework, and active inference. I explored their integration with neurophysiological mechanisms, focusing on the somato-cognitive action network (SCAN) and its role in sensorimotor integration, intention encoding, and the judgment of agency. Case studies, simulations, and XR-based rehabilitation paradigms using robotic haptics were used to illustrate theoretical concepts. The SoA emerges from hierarchical inference processes that combine top-down motor intentions with bottom-up sensory feedback. Predictive coding frameworks, especially when implemented via Kalman filters and LQG control, provide a mechanistic basis for modeling motor learning, error correction, and adaptive control. Disruptions in these inference processes underlie symptoms in disorders such as functional movement disorder. XR-based interventions using robotic interfaces can restore the SoA by modulating sensory precision and motor predictions through adaptive feedback and suggestion. Computer simulations demonstrate how internal models, and hypnotic suggestions influence state estimation, motor execution, and the recovery of agency. Predictive coding and active inference offer a powerful computational framework for understanding and enhancing the SoA in health and disease. The SCAN system serves as a neural hub for integrating motor plans with cognitive and affective processes. Future work should explore the real-time modulation of agency via biofeedback, simulation, and SCAN-targeted non-invasive brain stimulation.

Use of an abdominal binder in colonoscopies performed by trainees in gastrointestinal endoscopy: a randomized, double-blind, sham-controlled trial.

Colonoscopy is a widely used diagnostic and therapeutic tool for colonic diseases and serves as the preferred screening method for colorectal cancer (CRC). A common difficulty during colonoscopy is the looping of the colon, which can result in patient discomfort, prolonged cecal intubation time (CIT), and the need for auxiliary maneuvers. This study aimed to evaluate the efficacy and safety of using an abdominal binder during colonoscopy performed by trainees. This randomized, double-blind, sham-controlled trial was conducted at a tertiary center. Participants were outpatients aged 20-80 years undergoing elective colonoscopy. They were randomly assigned to either the abdominal binder (AB) group or the sham binder (SB) group. The primary outcome measured was cecal intubation time. Secondary outcomes included the need for manual abdominal compression and postural adjustments during the procedure. A total of 211 participants were enrolled in the study. The median CIT was significantly shorter in the AB group compared to the SB group (728 s vs. 774 s, p = 0.008). Additionally, the AB group demonstrated a significantly reduced need for manual abdominal compression (p ≤ 0.001) and postural adjustments (p = 0.01). The requirement for abdominal compression decreased by 40% (95% CI 27.7-52.9%), while the need for postural changes was reduced by 9.4% (95% CI 1.9-88.7%). The use of an abdominal binder during colonoscopy performed by trainees significantly reduced cecal intubation time and minimized the need for ancillary maneuvers, such as manual abdominal compression and postural adjustments.

The Effect of Coordination Dynamics Therapy on Posture and Stability in Adolescents

BackgroundScreening and early diagnosis of incorrect body posture in children and adolescents are crucial for identifying high-risk populations and implementing targeted interventions to prevent posture-related health complications. Coordination Dynamics Therapy (CDT) applies a biofeedback method that stimulates coordinated movements of the trunk and extremities to help correct posture.ObjectiveThis study aimed to evaluate the effects of CDT on posture and stability in adolescents with posture disorders and compare it with conventional kinesiotherapy (CON).MethodsForty patients (mean age 12.69 ± 1.70 years) were divided into two groups. The first group underwent 18 sessions of CDT, and the second group underwent 18 sessions of CON. Posture was assessed by measuring the spinal range of motion and performing muscle tests based on Janda’s approach. Stability was measured posturographically. Assessments were conducted within 24 h before and after the intervention.ResultsAfter 9–10 weeks, significant improvements in spinal range of motion, trunk muscle strength, and stability were observed in both groups (p < 0.05). The CDT group showed greater improvement in spinal range of motion (d = 1.005) and stability (d = 0.794), while the CON group demonstrated a more significant strengthening of weakened muscle groups (d = 1.69).ConclusionsCDT can be effectively integrated into rehabilitation programs for adolescents with posture disorders, complementing conventional kinesiotherapy. These findings support CDT as an affordable and effective therapeutic tool to enhance posture correction and stability.

Physical activity prescription in general practice in France: where do we stand? A cross-sectional study

BackgroundPhysical activity on prescription (PAP) is recognized as an effective preventive and therapeutic tool for various diseases, yet its application by general practitioners (GPs) varies widely. This study aims to analyse PAP usage practices among GPs in France, focusing on prescription frequency, targeted pathologies, and influencing factors. It also explores GPs’ perceptions of facilitators and barriers to PAP.MethodsA cross-sectional study was conducted between October 23, 2023, and April 23, 2024, collecting data from a sample of GPs across France. A structured questionnaire was used to assess the frequency of PAP usage, target populations, as well as GPs’ knowledge and perceived barriers to prescribing PA. Descriptive and analytical methods were employed to analyse the data, and logistic regression was used to examine associations between physician characteristics, PAP practices, and key barriers to prescribing.ResultsAmong respondents, 39.1% reported prescribing PAP, with a median prescription rate of approximately twice per month. Reduced sedentary behaviour (< 4 h) was significantly associated with a higher frequency of PAP (pOR 3.6, p = 0.044). Knowledge of a nearby sport-health facility strongly predicted prescription (pOR 3.7 p < 0.001). Prescription support tools positively influenced prescribing rates (pOR 1.6 p = 0.041). In contrast, GPs unaware of any tools prescribed significantly less.ConclusionThese findings suggest that improving access to sport-health facilities and providing GPs with effective support tools could significantly enhance PAP practices.

Dynamic Neutrophil Subsets and Function in Lung Transplant Recipients: Insights from a One-Year Longitudinal Pilot Study.

Background: Neutrophils are key innate immune cells in peripheral blood. In recent years, sub-populations of neutrophils have been identified. In addition to the normal-density neutrophils (NDNs) in both healthy subjects and patients, low-density neutrophils (LDNs) were described in chronic inflammation and cancer. In lung transplants (LTx), neutrophils play crucial roles in reperfusion injury, acute rejection, and chronic lung allograft dysfunction. Our pilot study examines neutrophil subsets and function in LTx recipients during the first post-transplant year. Methods: We collected blood from 11 LTx recipients at various intervals. LDNs and normal-density neutrophils (NDNs) were isolated. The production of reactive oxygen species (ROS) by NDNs was measured after PMA activation using a Luminol-HRP assay. Neutrophil phenotypic markers were analyzed with flow cytometry. Results: The LDN-to-NDN ratio increased at 3 and 6 months post-transplant. Expression levels of CD62-L (aging marker), PDL-1 (immune checkpoint), CD15 (maturation), and CXCR4 (homeostasis regulator) showed modulation. Interestingly, ROS production by NDNs was mildly elevated at baseline, reduced at 6 months, and returned to baseline levels by 9 months post-transplant. Conclusions: Neutrophils exhibit dynamic changes in the first post-LTx year. Investigating neutrophil plasticity could reveal clinically relevant biomarkers and facilitate the development of diagnostic and therapeutic tools in LTx.

Application of non‑coding RNAs in tumors (Review).

Tumors are associated with the highest mortality rates worldwide. For more than a decade, research has focused on the genetic involvement of proteins in cancer; however, a complete class of molecular non‑coding (nc)RNAs have been discovered in recent years, and these are considered to be associated with cancer. Notably, ncRNAs are highly conserved and multifunctional. These interact with multiple signaling pathways, influencing cell cycle progression and various physiological processes. Therefore, the present review aimed to investigate ncRNA, microRNA, transfer RNA‑derived small RNA, PIWI‑interacting RNA and long non‑coding RNA to further understand the associated generation processes, functional mechanisms and therapeutic roles in tumors. The present review demonstrated the critical role of ncRNAs in tumors, and may provide a novel theoretical basis for the role of ncRNAs as biomarkers or therapeutic tools in the treatment of cancer.

Exploring User Perspectives on Virtual Reality as a Therapeutic Tool for Chronic Pain Management.

Chronic pain affects over 20% of the global population, significantly impairing the quality of life and increasing healthcare costs. Virtual Reality (VR) shows promise as an innovative, non-invasive tool for chronic pain management by modulating pain perception, and helping in promoting coping strategies such as relaxation. This study explores the use, willingness to adopt, and preferences for VR of people with chronic pain. This mixed-methods study included an online survey (OS-answered by 511 participants with chronic pain) and two focus groups (FG-including a total of 17 people with fibromyalgia). The OS was created to assess their use of VR, willingness to adopt, preferences, and advantages/disadvantages. The FG was designed to gain a more in depth knowledge of these variables. Descriptive analyses were conducted with the results from the OS, while FG transcripts were thematically analysed to identify key insights and patterns. VR was largely unfamiliar (only 23.1% had previously used it) but considered as promising for remote, low-risk therapy, valuing aspects such as portability, minimal side effects, and immersive experiences. Factors related to usability challenges, stigma, and limited professional training were probably related to the lack of use of VR. Key concerns included reduced therapist contact, social isolation, and usability challenges. Preferences were balanced between standalone and smartphone-based systems, with cost and accessibility being major factors. Participants emphasized the importance of tailored designs, user-friendly, affordable options, and maintaining therapist interaction, offering valuable insights for integrating VR effectively into healthcare. The findings of this study highlight the need to potentiate the transfer of results to clinical practice. It is also fundamental to work to reduce the stigma and include the use of Information and Communication Technologies in pain curricula.

Unveiling the Protective Roles of Melatonin on Glial Cells in the Battle Against Alzheimer's Disease-Insights from In Vivo and In Vitro Studies.

Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disorder that predominantly affects the elderly. Characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles, AD leads to memory loss, cognitive decline, and severe behavioral changes. As the most common form of dementia, AD imposes a significant global health burden, highlighting the need for interventions that address underlying disease mechanisms rather than only symptomatic treatment. Glial cells, including microglia and astrocytes, play a crucial role in AD progression by mediating neuroinflammatory responses and modulating Aβ clearance and neuronal health. Dysfunction in these cells can exacerbate neuroinflammation and neuronal damage, making glial cells an important target for therapeutic intervention. This review synthesizes findings from in vivo and in vitro studies on melatonin's effects on glial cell dysfunction in AD, emphasizing the multi-mechanistic nature of its neuroprotective properties. Recent studies highlight melatonin's potential as a therapeutic agent that addresses AD-related mechanisms through its interactions with glial cells. Melatonin has demonstrated protective effects, including reducing oxidative stress, apoptosis, and inflammation, inhibiting Aβ fibrillogenesis, and modulating amyloid precursor proteins. Additionally, its influence on glial cell activity, through melatonin receptor pathways, suggests it can alleviate neuroinflammation, a key component of AD progression. The collective evidence points to melatonin's promise as a therapeutic tool with potential roles in both preventive and adjunctive treatments for AD. However, further research is necessary to establish its efficacy and safety in clinical settings.