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13 pages, 1769 KiB  
Article
Antimicrobial Photodynamic Activity of the Zn(II) Phthalocyanine RLP068/Cl Versus Antimicrobial-Resistant Priority Pathogens
by Ilaria Baccani, Sara Cuffari, Francesco Giuliani, Gian Maria Rossolini and Simona Pollini
Int. J. Mol. Sci. 2025, 26(15), 7545; https://doi.org/10.3390/ijms26157545 (registering DOI) - 5 Aug 2025
Abstract
The emergence and spread of antimicrobial resistance among pathogens are significantly reducing available therapeutic options, highlighting the urgent need for novel and complementary treatment strategies. Antimicrobial photodynamic therapy (aPDT) is a promising alternative approach that can overcome antimicrobial resistance through a multitarget mechanism [...] Read more.
The emergence and spread of antimicrobial resistance among pathogens are significantly reducing available therapeutic options, highlighting the urgent need for novel and complementary treatment strategies. Antimicrobial photodynamic therapy (aPDT) is a promising alternative approach that can overcome antimicrobial resistance through a multitarget mechanism of action, exerting direct bactericidal and fungicidal effects with minimal risk of resistance development. Although aPDT has shown efficacy against a variety of pathogens, data on its activity against large collections of clinical multidrug-resistant strains are still limited. In this study, we assessed the antimicrobial activity of the photosensitizer RLP068/Cl combined with a red light-emitting LED source at 630 nm (Molteni Farmaceutici, Italy) against a large panel of Gram-negative and Gram-positive bacterial strains harboring relevant resistance traits and Candida species. Our results demonstrated the significant microbicidal activity of RLP068/Cl against all of the tested strains regardless of their resistance phenotype, with particularly prominent activity against Gram-positive bacteria (range of bactericidal concentrations 0.05–0.1 µM), which required significantly lower exposure to photosensitizer compared to Candida and Gram-negative species (range 5–20 µM). Overall, these findings support the potential use of RLP068/Cl-mediated aPDT as an effective therapeutic strategy for the management of localized infections caused by MDR organisms, particularly when conventional therapeutic options are limited. Full article
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18 pages, 2038 KiB  
Article
Effects of 12-Week Infant Shantala Massage Program on Maternal Emotional Well-Being Following First-Time Birth
by Anna Gogola and Rafał Gnat
Healthcare 2025, 13(15), 1895; https://doi.org/10.3390/healthcare13151895 - 3 Aug 2025
Viewed by 47
Abstract
Background/Objectives: This study aimed to determine whether postpartum mothers exhibit a uniform trajectory of postpartum emotional status (PES) changes or if distinct subgroups with differing trajectories of PES exist. Additionally, it investigated whether intensified tactile stimulation of the infant through Shantala massage influences [...] Read more.
Background/Objectives: This study aimed to determine whether postpartum mothers exhibit a uniform trajectory of postpartum emotional status (PES) changes or if distinct subgroups with differing trajectories of PES exist. Additionally, it investigated whether intensified tactile stimulation of the infant through Shantala massage influences maternal PES. Method: A quasi-experimental design with a matched control group was employed. Eighty women following their first physiological delivery volunteered to participate. The intervention involved applying intensified tactile stimulation to the infant via Shantala massage over a 12-week postpartum period. Maternal PES, divided into negative and positive emotional domains, was assessed using four standardized questionnaires. Results: Two opposing trajectories of PES change were identified: adverse and favorable. Intensified tactile stimulation was associated with improvement in maternal emotional status along both trajectories. Conclusions: PES changes do not follow a uniform course across all women; notably, those with a favorable trajectory often begin with more severe symptoms. Overlooking this distinction in diagnosis, prevention, and treatment may result in suboptimal care. The factors influencing PES trajectories remain unidentified but may affect clinical intervention outcomes. The Shantala massage intervention appears to slow the progression of emotional disorders in women with adverse PES changes and accelerate recovery in those with favorable changes. Implementation of this approach in clinical settings is recommended. Full article
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12 pages, 855 KiB  
Article
Application of Integrative Medicine in Plastic Surgery: A Real-World Data Study
by David Lysander Freytag, Anja Thronicke, Jacqueline Bastiaanse, Ioannis-Fivos Megas, David Breidung, Ibrahim Güler, Harald Matthes, Sophia Johnson, Friedemann Schad and Gerrit Grieb
Medicina 2025, 61(8), 1405; https://doi.org/10.3390/medicina61081405 - 1 Aug 2025
Viewed by 137
Abstract
Background and Objectives: There is a global rise of public interest in integrative medicine. The principles of integrative medicine combining conventional medicine with evidence-based complementary therapies have been implemented in many medical areas, including plastic surgery, to improve patient’s outcome. The aim [...] Read more.
Background and Objectives: There is a global rise of public interest in integrative medicine. The principles of integrative medicine combining conventional medicine with evidence-based complementary therapies have been implemented in many medical areas, including plastic surgery, to improve patient’s outcome. The aim of the present study was to systematically analyze the application and use of additional non-pharmacological interventions (NPIs) of patients of a German department of plastic surgery. Materials and Methods: The present real-world data study utilized data from the Network Oncology registry between 2016 and 2021. Patients included in this study were at the age of 18 or above, stayed at the department of plastic surgery and received at least one plastic surgical procedure. Adjusted multivariable logistic regression analyses were performed to detect associations between the acceptance of NPIs and predicting factors such as age, gender, year of admission, or length of hospital stay. Results: In total, 265 patients were enrolled in the study between January 2016 and December 2021 with a median age of 65 years (IQR: 52–80) and a male/female ratio of 0.77. Most of the patients received reconstructive surgery (90.19%), followed by hand surgery (5.68%) and aesthetic surgery (2.64%). In total, 42.5% of the enrolled patients accepted and applied NPIs. Physiotherapy, rhythmical embrocations, and compresses were the most often administered NPIs. Conclusions: This exploratory analysis provides a descriptive overview of the application and acceptance of NPIs in plastic surgery patients within a German integrative care setting. While NPIs appear to be well accepted by a subset of patients, further prospective studies are needed to evaluate their impact on clinical outcomes such as postoperative recovery, pain management, patient-reported quality of life, and overall satisfaction with care. Full article
(This article belongs to the Section Surgery)
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14 pages, 898 KiB  
Article
Cardiovascular Risk in Rheumatic Patients Treated with JAK Inhibitors: The Role of Traditional and Emerging Biomarkers in a Pilot Study
by Diana Popescu, Minerva Codruta Badescu, Elena Rezus, Daniela Maria Tanase, Anca Ouatu, Nicoleta Dima, Oana-Nicoleta Buliga-Finis, Evelina Maria Gosav, Damiana Costin and Ciprian Rezus
J. Clin. Med. 2025, 14(15), 5433; https://doi.org/10.3390/jcm14155433 - 1 Aug 2025
Viewed by 150
Abstract
Background: Despite therapeutic advances, morbidity and mortality remain high in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), primarily due to increased cardiovascular risk. Objectives: Our study aimed to evaluate the cardiovascular risk profile and biomarker dynamics in patients with RA and [...] Read more.
Background: Despite therapeutic advances, morbidity and mortality remain high in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), primarily due to increased cardiovascular risk. Objectives: Our study aimed to evaluate the cardiovascular risk profile and biomarker dynamics in patients with RA and PsA treated with Janus kinase inhibitors (JAKis). To our knowledge, this is the first study assessing Lp(a) levels in this context. Methods: This prospective, observational study assessed 48 adult patients. The follow-up period was 12 months. Traditional cardiovascular risk factors and biological markers, including lipid profile, lipoprotein(a) [Lp(a)], and uric acid (UA), were assessed at baseline and follow-up. Correlations between JAKi therapy, lipid profile changes, and cardiovascular risk factors were investigated. Cox regression analysis was used to identify predictors of non-major cardiovascular events. Results: A strong positive correlation was observed between baseline and 12-month Lp(a) levels (r = 0.926), despite minor statistical shifts. No major cardiovascular events occurred during follow-up; however, 47.9% of patients experienced non-major cardiovascular events (e.g., uncontrolled arterial hypertension, exertional angina, and new-onset arrhythmias). Active smoking [hazard ratio (HR) 9.853, p = 0.005], obesity (HR 3.7460, p = 0.050), and arterial hypertension (HR 1.219, p = 0.021) were independent predictors of these events. UA (HR 1.515, p = 0.040) and total cholesterol (TC) (HR 1.019, p = 0.034) were significant biochemical predictors as well. Elevated baseline Lp(a) combined with these factors was associated with an increased event rate, particularly after age 60. Conclusions: Traditional cardiovascular risk factors remain highly prevalent and predictive, underscoring the need for comprehensive cardiovascular risk management. Lp(a) remained stable and may serve as a complementary biomarker for risk stratification in JAKi-treated patients. Full article
(This article belongs to the Section Immunology)
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14 pages, 1399 KiB  
Article
GSTM5 as a Potential Biomarker for Treatment Resistance in Prostate Cancer
by Patricia Porras-Quesada, Lucía Chica-Redecillas, Beatriz Álvarez-González, Francisco Gutiérrez-Tejero, Miguel Arrabal-Martín, Rosa Rios-Pelegrina, Luis Javier Martínez-González, María Jesús Álvarez-Cubero and Fernando Vázquez-Alonso
Biomedicines 2025, 13(8), 1872; https://doi.org/10.3390/biomedicines13081872 - 1 Aug 2025
Viewed by 169
Abstract
Background/Objectives: Androgen deprivation therapy (ADT) is widely used to manage prostate cancer (PC), but the emergence of treatment resistance remains a major clinical challenge. Although the GST family has been implicated in drug resistance, the specific role of GSTM5 remains poorly understood. [...] Read more.
Background/Objectives: Androgen deprivation therapy (ADT) is widely used to manage prostate cancer (PC), but the emergence of treatment resistance remains a major clinical challenge. Although the GST family has been implicated in drug resistance, the specific role of GSTM5 remains poorly understood. This study investigates whether GSTM5, alone or in combination with clinical variables, can improve patient stratification based on the risk of early treatment resistance. Methods: In silico analyses were performed to examine GSTM5’s role in protein interactions, molecular pathways, and gene expression. The rs3768490 polymorphism was genotyped in 354 patients with PC, classified by ADT response. Descriptive analysis and logistic regression models were applied to evaluate associations between genotype, clinical variables, and ADT response. GSTM5 expression related to the rs3768490 genotype and ADT response was also analyzed in 129 prostate tissue samples. Results: The T/T genotype of rs3768490 was significantly associated with a lower likelihood of early ADT resistance in both individual (p = 0.0359, Odd Ratios (OR) = 0.18) and recessive models (p = 0.0491, OR = 0.21). High-risk classification according to D’Amico was strongly associated with early progression (p < 0.0004; OR > 5.4). Combining genotype and clinical risk improved predictive performance, highlighting their complementary value in stratifying patients by treatment response. Additionally, GSTM5 expression was slightly higher in T/T carriers, suggesting a potential protective role against ADT resistance. Conclusions: The T/T genotype of rs3768490 may protect against ADT resistance by modulating GSTM5 expression in PC. These preliminary findings highlight the potential of integrating genetic biomarkers into clinical models for personalized treatment strategies, although further studies are needed to validate these observations. Full article
(This article belongs to the Special Issue Molecular Biomarkers of Tumors: Advancing Genetic Studies)
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14 pages, 2265 KiB  
Communication
Bioelectrical Impedance Assessment in a Patient with Breast Cancer: A Case Report on the Effect of Integrative Therapies on Cellular Homeostasis
by Graziella Marino, Giovanni Pace, Lucia Sabato, Marzia Sichetti and Marisabel Mecca
Nutrients 2025, 17(15), 2506; https://doi.org/10.3390/nu17152506 - 30 Jul 2025
Viewed by 137
Abstract
Background/Objectives: Since breast cancer (BC) survival rates have increased to 91% at 5 years and 80% at 15 years postdiagnosis, there is a growing awareness of the importance of addressing the long-term well-being of patients. Consequently, integrative oncology, which combines standard therapies [...] Read more.
Background/Objectives: Since breast cancer (BC) survival rates have increased to 91% at 5 years and 80% at 15 years postdiagnosis, there is a growing awareness of the importance of addressing the long-term well-being of patients. Consequently, integrative oncology, which combines standard therapies with complementary approaches (nutrition, mind–body practices, and lifestyle modifications), has emerged as a patient-centred model aimed at improving symptom management, treatment adherence, and overall quality of life (QoL). This study aims to demonstrate how integrative therapies can benefit body composition, phase angle, and fluid and electrolyte balance through bioelectrical impedance analysis (BIA). Methods: This study considers a patient who underwent BC surgery and was enrolled in the AMICO clinic for anamnesis, as well as their oncological pathology data, assessment of QoL, and BIA. The breast surgeon specialising in integrative oncology therapies prescribed the patient curcumin and polydatin, moderate physical activity, a balanced diet, and Qigong sessions. The patient underwent monitoring through haematochemical analysis, BIA, and a QoL questionnaire, with follow-up every four months. Results: Between 4 and 12 months, fat mass (FM) and body mass index (BMI) markedly decreased, whereas fat-free mass (FFM), total body water (TBW), and skeletal muscle mass (SMM) increased progressively. Moreover, the improvements in the Na/K ratio and phase angle (PhA) suggest a shift toward better electrolyte and fluid balance and enhanced cellular integrity and membrane function. Equally outstanding were her psychological benefits in terms of mood, sleep, anxiety, and melancholy. Conclusions: Patient progress in body composition, metabolic function, pain management, and psychological status measured during the 12-month follow-up demonstrates the potential benefits of an integrative approach to supportive cancer care. Full article
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12 pages, 753 KiB  
Article
Reducing State and Trait Anxiety Through Art Therapy in Adolescents with Eating Disorders: Results from a Pilot Repeated-Measures Study
by Francesco Monaco, Annarita Vignapiano, Stefania Landi, Ernesta Panarello, Benedetta Di Gruttola, Naomi Gammella, Silvia Adiutori, Eleonora Acierno, Valeria Di Stefano, Ilaria Pullano, Giulio Corrivetti and Luca Steardo Jr
J. Clin. Med. 2025, 14(15), 5298; https://doi.org/10.3390/jcm14155298 - 27 Jul 2025
Viewed by 399
Abstract
Background: Art therapy is increasingly recognized as a valuable complementary intervention for individuals with eating disorders (EDs), who frequently experience comorbid anxiety and difficulties with emotional regulation. However, few studies have examined its short-term effects on state and trait anxiety within structured clinical [...] Read more.
Background: Art therapy is increasingly recognized as a valuable complementary intervention for individuals with eating disorders (EDs), who frequently experience comorbid anxiety and difficulties with emotional regulation. However, few studies have examined its short-term effects on state and trait anxiety within structured clinical settings. Methods: This pilot study involved 19 adolescent females (mean age 17.7 ± 2.1 years) diagnosed with anorexia nervosa (AN) or bulimia nervosa (BN) and admitted to the Mariconda Regional Residence for Eating Disorders (ASL Salerno, Italy) in residential or semi-residential treatment. Participants completed a structured six-week cycle of weekly textile-based art therapy sessions, designed to promote emotional expression and body reconnection. State and trait anxiety levels were assessed pre- and post-session using the State-Trait Anxiety Inventory (STAI). Repeated-measures ANOVA was used to analyze state anxiety changes; a linear mixed-effects model was applied to trait anxiety. Results: State anxiety significantly decreased immediately after sessions (p = 0.002). A significant main effect of session (p = 0.01) and a time × session interaction (p = 0.025) indicated variability across sessions. Trait anxiety showed a non-significant trend toward reduction (p = 0.11); however, reductions were significant at sessions 4 (p = 0.015), 5 (p < 0.001), and 6 (p = 0.005). Conclusions: Art therapy may offer immediate reductions in state anxiety and may contribute to a longer-term reduction in trait anxiety with 4–6 sessions. These findings support integrating creative interventions within multidisciplinary ED treatment programs. Future research with larger samples and control groups is needed to confirm and expand upon these preliminary results. Full article
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34 pages, 924 KiB  
Review
Three-Dimensional Disassemblable Scaffolds for Breast Reconstruction
by Viktoriia Kiseleva, Aida Bagdasarian, Polina Vishnyakova, Andrey Elchaninov, Victoria Karyagina, Valeriy Rodionov, Timur Fatkhudinov and Gennady Sukhikh
Polymers 2025, 17(15), 2036; https://doi.org/10.3390/polym17152036 - 25 Jul 2025
Viewed by 516
Abstract
In recent years, significant progress has been made in breast reconstructive surgery, particularly with the use of three-dimensional (3D) disassemblable scaffolds. Reconstructive plastic surgery aimed at restoring the shape and size of the mammary gland offers medical, psychological, and social benefits. Using autologous [...] Read more.
In recent years, significant progress has been made in breast reconstructive surgery, particularly with the use of three-dimensional (3D) disassemblable scaffolds. Reconstructive plastic surgery aimed at restoring the shape and size of the mammary gland offers medical, psychological, and social benefits. Using autologous tissues allows surgeons to recreate the appearance of the mammary gland and achieve tactile sensations similar to those of a healthy organ while minimizing the risks associated with implants; 3D disassemblable scaffolds are a promising solution that overcomes the limitations of traditional methods. These constructs offer the potential for patient-specific anatomical adaptation and can provide both temporary and long-term structural support for regenerating tissues. One of the most promising approaches in post-mastectomy breast reconstruction involves the use of autologous cellular and tissue components integrated into either synthetic scaffolds—such as polylactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), and polycaprolactone (PCL)—or naturally derived biopolymer-based matrices, including alginate, chitosan, hyaluronic acid derivatives, collagen, fibrin, gelatin, and silk fibroin. In this context, two complementary research directions are gaining increasing significance: (1) the development of novel hybrid biomaterials that combine the favorable characteristics of both synthetic and natural polymers while maintaining biocompatibility and biodegradability; and (2) the advancement of three-dimensional bioprinting technologies for the fabrication of patient-specific scaffolds capable of incorporating cellular therapies. Such therapies typically involve mesenchymal stromal cells (MSCs) and bioactive signaling molecules, such as growth factors, aimed at promoting angiogenesis, cellular proliferation, and lineage-specific differentiation. In our review, we analyze existing developments in this area and discuss the advantages and disadvantages of 3D disassemblable scaffolds for mammary gland reconstruction, as well as prospects for their further research and clinical use. Full article
(This article belongs to the Section Biobased and Biodegradable Polymers)
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12 pages, 632 KiB  
Article
Tailoring Inflammatory Biomarker Assessment in Axial Spondyloarthritis: A Comparative Study of Erythrocyte Sedimentation Rate and C-Reactive Protein Across Disease Profiles
by Rubén Queiro, Sara Alonso, Stefanie Burger, Estefanía Pardo, Ignacio Braña, Marta Loredo and Mercedes Alperi
J. Pers. Med. 2025, 15(8), 329; https://doi.org/10.3390/jpm15080329 - 25 Jul 2025
Viewed by 254
Abstract
Background: Personalized medicine in axial spondyloarthritis (axSpA) requires accurate tools to assess inflammation and tailor disease monitoring. The role of traditional biomarkers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) remains controversial due to limited sensitivity and variability across disease [...] Read more.
Background: Personalized medicine in axial spondyloarthritis (axSpA) requires accurate tools to assess inflammation and tailor disease monitoring. The role of traditional biomarkers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) remains controversial due to limited sensitivity and variability across disease profiles. Objective: To compare the performance of ESR and CRP in different clinical scenarios of axSpA, including disease activity, functional impact, severity, disease duration, and exposure to biologic therapy. Methods: We conducted a cross-sectional analysis of 330 patients with axSpA. Correlations among ESR, CRP, and composite disease indices were evaluated. The discriminatory capacity of each biomarker for relevant clinical thresholds was analyzed using ROC curves and optimal cut-offs identified by the Youden index. Results: ESR showed broader correlations with disease impact and activity scores than CRP. While both markers had low sensitivity overall, they were highly specific for identifying patients with very high disease activity in select scenarios. ESR ≥ 8.5 mm/h and CRP ≥ 1.88 mg/dL were strongly discriminatory in patients not exposed to biologics. CRP ≥ 0.56 mg/dL showed good performance in early disease. Conclusions: Both ESR and CRP provide complementary insights into disease activity in axSpA. ESR may offer a broader reflection of disease burden beyond inflammation. These results support a more personalized biomarker strategy in real-world axSpA management, adapted to patient profile and treatment context. Full article
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15 pages, 302 KiB  
Review
Pruritus in Palliative Care: A Narrative Review of Essential Oil-Based Strategies to Alleviate Cutaneous Discomfort
by Sara Diogo Gonçalves
Diseases 2025, 13(8), 232; https://doi.org/10.3390/diseases13080232 - 23 Jul 2025
Viewed by 223
Abstract
Pruritus is a common and distressing symptom in palliative care, often resulting from complex underlying conditions such as cancer, chronic kidney disease, and liver failure. Conventional pharmacological treatments frequently offer limited relief and may produce undesirable side effects in this medically fragile population. [...] Read more.
Pruritus is a common and distressing symptom in palliative care, often resulting from complex underlying conditions such as cancer, chronic kidney disease, and liver failure. Conventional pharmacological treatments frequently offer limited relief and may produce undesirable side effects in this medically fragile population. Despite the high prevalence and impact of pruritus in palliative care, there is a lack of consolidated evidence on integrative non-pharmacological approaches. This narrative review explores the potential role of essential oils as a complementary approach to managing pruritus in palliative settings. A review of the literature was conducted to examine the mechanisms of action, safety considerations, and clinical outcomes associated with the use of essential oils, with a particular focus on their anti-inflammatory, neuromodulatory, and soothing properties. Evidence suggests that essential oils may provide symptom relief and enhance quality of life when integrated into multidisciplinary care; however, small sample sizes, heterogeneity, and methodological weaknesses often limit the findings of these studies. Furthermore, the long-term safety and antigenotoxic potential of essential oils remain underexplored. This narrative review concludes that while essential oils appear promising as adjunct therapies for pruritus, further rigorous research, particularly well-designed clinical trials and toxicological assessments, is needed to support their safe and effective use in palliative care. Full article
17 pages, 3138 KiB  
Article
Unclassified Chromosomal Abnormalities as an Indicator of Genomic Damage in Survivors of Hodgkin’s Lymphoma
by Sandra Ramos, Bertha Molina, María del Pilar Navarrete-Meneses, David E. Cervantes-Barragan, Valentín Lozano and Sara Frias
Cancers 2025, 17(15), 2437; https://doi.org/10.3390/cancers17152437 - 23 Jul 2025
Viewed by 269
Abstract
Background/Objectives: Hodgkin’s lymphoma (HL) affects 2–4 individuals per 100,000 annually. Standard treatment includes radiotherapy and ABVD chemotherapy, achieving a 95% survival rate. However, HL survivors face an elevated risk of treatment-related morbidity, particularly the development of secondary malignancies. Previous studies have demonstrated [...] Read more.
Background/Objectives: Hodgkin’s lymphoma (HL) affects 2–4 individuals per 100,000 annually. Standard treatment includes radiotherapy and ABVD chemotherapy, achieving a 95% survival rate. However, HL survivors face an elevated risk of treatment-related morbidity, particularly the development of secondary malignancies. Previous studies have demonstrated that ABVD treatment induces a high frequency of chromosomal aberrations (CAs) in lymphocytes from HL patients, with higher frequencies one year after treatment than during treatment. This study aimed to determine whether HL treatment also induces unclassified chromosomal/nuclear aberrations (UnCAs) in the lymphocytes of HL patients, and whether these alterations may serve as complementary indicators of genomic instability. Methods: Peripheral blood lymphocytes from HL patients were collected at three time points: before treatment (BT), during treatment (DT), and one year after treatment (1yAT) with ABVD chemotherapy and radiotherapy. A minimum of 3000 nuclei were analyzed per patient to identify and quantify UnCAs. These results were compared to UnCA frequencies in healthy individuals. Results: The percentage of cells presenting UnCAs per 3000 nuclei was 23.92% BT, 18.58% DT, and 30.62% 1yAT. All values were significantly higher (p < 0.016) than the 8.16% observed in healthy controls. The increase was primarily driven by free chromatin and micronuclei clusters. UnCA frequency was lower during treatment than one year after, likely due to the elimination of highly damaged cells through apoptosis or lack of proliferative capacity. Over time, however, persistent genomic damage appears to accumulate in surviving cells, becoming more evident post-treatment. A parallel trend was observed between the frequencies of UnCAs free chromatin, micronucleus and micronuclei clusters, and classical CAs, showing a similar pattern of genomic damage induced by therapy. Conclusions: The post-treatment increase in UnCAs indicates ongoing genomic instability, possibly driven by the selective survival of hematopoietic stem cells with higher genomic fitness. Given their persistence and association with therapy-induced damage, free chromatin and micronuclei clusters may serve as early biomarkers for secondary cancer risk in HL survivors. Full article
(This article belongs to the Special Issue The Role of Chromosomal Instability in Cancer: 2nd Edition)
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20 pages, 3781 KiB  
Article
Ginsenoside Rg3 Adjunctively Increases the Efficacy of Gefitinib Against NSCLC by Regulating EGFR Copy Number
by Xinyi Lv, Yuehan Song, Tianhua Liu, Dingdan Zhang, Xinpeng Ye, Qingqing Wang, Rongrong Li, Jiayi Chen, Shujing Zhang, Xue Yu and Chunying Hou
Pharmaceuticals 2025, 18(7), 1077; https://doi.org/10.3390/ph18071077 - 21 Jul 2025
Viewed by 304
Abstract
Background: Lung cancer has the highest morbidity and mortality of all tumors, and the development of TKI drugs targeting EGFR activating mutations has brought lung cancer treatment into the targeted era. In view of their low efficacy and susceptibility to drug resistance, [...] Read more.
Background: Lung cancer has the highest morbidity and mortality of all tumors, and the development of TKI drugs targeting EGFR activating mutations has brought lung cancer treatment into the targeted era. In view of their low efficacy and susceptibility to drug resistance, there is an urgent need to find strategies to increase their efficacy and reduce the incidence of drug resistance. Methods: In this study, we examined the distribution and probability of EGFR mutations in non-small cell lung cancer patients in the cBioPortal database and compared the survival prognosis of patients with normal and abnormal EGFR, NSCLC patients treated with and without TKI, and NSCLC patients with different EGFR gene copy numbers. We established a mouse lung cancer model and examined the histomorphological characteristics of lung tissues via hematoxylin and eosin staining. Additionally, changes in the copy number of the EGFR gene and its protein expression levels were detected using RT-qPCR and Western blotting. Furthermore, we quantified the concentration of the EGFR protein using ELISA. Results: We found no significant advantage of EGFR-TKI therapy over first-line chemotherapeutic agents in patients with EGFR-abnormal NSCLC. The reason for this may be related to the abnormal EGFR gene copy number; the higher the copy number increases, the worse the survival prognosis of the patients. In molecular biology experiments, we demonstrated that ginsenoside Rg3 down-regulated the copy number of 18, 19, 20, and 21 exons and protein expression of EGFR in lung adenocarcinoma cells. The results of in vivo pharmacodynamic assays confirmed that sequential administration of ginsenoside Rg3 with TKI drugs could achieve a gainful complementary effect. Conclusions: Ginsenoside Rg3 down-regulates the copy number of EGFR important exons in EGFR-mutant cells of lung adenocarcinoma and reduces EGFR protein expression, thus providing a high gainful complementary effect in combination with EGFR-TKI. Full article
(This article belongs to the Topic Advances in Anti-Cancer Drugs: 2nd Edition)
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20 pages, 4705 KiB  
Article
GRK5 as a Novel Therapeutic Target for Immune Evasion in Testicular Cancer: Insights from Multi-Omics Analysis and Immunotherapeutic Validation
by Congcong Xu, Qifeng Zhong, Nengfeng Yu, Xuqiang Zhang, Kefan Yang, Hao Liu, Ming Cai and Yichun Zheng
Biomedicines 2025, 13(7), 1775; https://doi.org/10.3390/biomedicines13071775 - 21 Jul 2025
Viewed by 356
Abstract
Background: Personalized anti-tumor therapy that activates the immune response has demonstrated clinical benefits in various cancers. However, its efficacy against testicular cancer (TC) remains uncertain. This study aims to identify suitable patients for anti-tumor immunotherapy and to uncover potential therapeutic targets in TC [...] Read more.
Background: Personalized anti-tumor therapy that activates the immune response has demonstrated clinical benefits in various cancers. However, its efficacy against testicular cancer (TC) remains uncertain. This study aims to identify suitable patients for anti-tumor immunotherapy and to uncover potential therapeutic targets in TC for the development of tailored anti-tumor immunotherapy. Methods: Consensus clustering analysis was conducted to delineate immune subtypes, while weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, and support vector machine (SVM) algorithms were employed to evaluate the potential efficacy of anti-tumor immunotherapy. Candidate immunotherapy targets were systematically identified through multi-gene panel analyses and subsequently validated using molecular biology assays. A prioritized target emerging from cellular screening was further evaluated for its capacity to potentiate anti-tumor immunity. The therapeutic efficacy of this candidate was rigorously confirmed through a comprehensive suite of immunological experiments. Results: Following systematic screening of five candidate genes (WNT11, FAM181B, GRK5, FSCN1, and ECHS1), GRK5 emerged as a promising therapeutic target for immunotherapy based on its distinct functional and molecular associations with immune evasion mechanisms. Cellular functional assays revealed that GRK5 knockdown significantly attenuated the malignant phenotype of testicular cancer cells, as evidenced by reduced proliferative capacity and invasive potential. Complementary immunological validation established that specific targeting of GRK5 with the selective antagonist GRK5-IN-2 disrupts immune evasion pathways in testicular cancer, as quantified by T-cell-mediated cytotoxicity. Conclusions: These findings position GRK5 as a critical modulator of tumor-immune escape, warranting further preclinical exploration of GRK5-IN-2 as a candidate immunotherapeutic agent. Full article
(This article belongs to the Section Immunology and Immunotherapy)
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30 pages, 11312 KiB  
Article
Study on the Mechanism and Dose–Effect Relationship of Flavonoids in Different Extracts of Radix Hedysari Against Gastrointestinal Injury Induced by Chemotherapy
by Shasha Zhao, Miaomiao Yang, Zimu Yang, Hai He, Ziyang Wang, Xinyu Zhu, Zhijia Cui and Jing Shao
Pharmaceuticals 2025, 18(7), 1072; https://doi.org/10.3390/ph18071072 - 20 Jul 2025
Viewed by 336
Abstract
Background: Previous studies have shown Radix Hedysari (RH)’s gastroprotective potential, but its active components and mechanisms remain uncharacterized. This study aimed to identify RH’s bioactive fractions, elucidate protection mechanisms, establish flavonoid dose-effect relationships, and determine the pharmacodynamic basis. Methods: Chemical profiling quantified [...] Read more.
Background: Previous studies have shown Radix Hedysari (RH)’s gastroprotective potential, but its active components and mechanisms remain uncharacterized. This study aimed to identify RH’s bioactive fractions, elucidate protection mechanisms, establish flavonoid dose-effect relationships, and determine the pharmacodynamic basis. Methods: Chemical profiling quantified eight flavonoids via HPLC. Network pharmacology screened targets/pathways using TCMSP, GeneCards databases. In vivo validation employed cisplatin–induced injury models in Wistar rats (n = 10/group). Assessments included: behavioral monitoring; organ indices; ELISA (MTL, VIP, IFN–γ, IgG, IL–6, TNF–α etc.); H&E; and Western blot:(SCF, c–Kit, p65). Dose–effect correlations were analyzed by PLS–DA. Results: Content determination indicated that Calycosin–7–glucoside and Ononin were notably enriched on both the n–BuOH part and the EtOAc part. Network pharmacology identified 5 core flavonoids and 8 targets enriched in IL–17/TNF signaling pathways. n–BuOH treatment minimized weight loss vs. MCG, increased spleen/thymus indices. n–BuOH and HPS normalized gastrointestinal, immune, inflammatory biomarkers (p < 0.01 vs. MCG). Histopathology confirmed superior mucosal protection in n–BuOH group vs. MCG. Western blot revealed n–BuOH significantly downregulated SCF, c–kit, and p65 expressions in both gastric and intestinal tissues (p < 0.001 vs. MCG). PLS–DA demonstrated Calycosin–7–glucoside had the strongest dose–effect correlation (VIP > 1) with protective outcomes. Conclusions: The n–BuOH fraction of RH is the primary bioactive component against chemotherapy–induced gastrointestinal injury, with Calycosin–7–glucoside as its key effector. Protection is mediated through SCF/c–Kit/NF–κB pathway inhibition, demonstrating significant dose–dependent efficacy. These findings support RH’s potential as a complementary therapy during chemotherapy. Full article
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16 pages, 2427 KiB  
Review
Pancreatic Cancer Resectability After Neoadjuvant Treatment: An Imaging Challenge
by Ioannis Christofilis, Charikleia Triantopoulou and Spiros Delis
Diagnostics 2025, 15(14), 1810; https://doi.org/10.3390/diagnostics15141810 - 18 Jul 2025
Viewed by 437
Abstract
Background: Assessing pancreatic ductal adenocarcinoma (PDAC) resectability after neoadjuvant therapy (NAT) remains a diagnostic challenge. Traditional computed tomography (CT) criteria often fail to distinguish viable tumor from fibrosis, necessitating a reassessment of imaging-based standards. Methods: A comprehensive literature review was conducted using PubMed, [...] Read more.
Background: Assessing pancreatic ductal adenocarcinoma (PDAC) resectability after neoadjuvant therapy (NAT) remains a diagnostic challenge. Traditional computed tomography (CT) criteria often fail to distinguish viable tumor from fibrosis, necessitating a reassessment of imaging-based standards. Methods: A comprehensive literature review was conducted using PubMed, focusing on prospective and retrospective studies over the past 25 years that evaluated the role of CT and complementary imaging modalities (MRI, PET-CT) in predicting resectability post-NAT in non-metastatic PDAC. Studies with small sample sizes or case reports were excluded. Results: Across studies, conventional CT parameters—particularly >180° vascular encasement—showed a limited correlation with histologic invasion or surgical outcomes after NAT. Persistent vessel contact on CT often reflected fibrosis, rather than active tumor. Dynamic changes, such as regression in the tumor–vessel interface and vessel lumen restoration, correlated more accurately with R0 resection. Adjunct markers like CA 19-9 response and patient performance status further improved resectability prediction. Conclusions: CT-based resectability assessment after NAT should transition from static morphologic criteria to response-based interpretation. Multidisciplinary evaluation integrating radiologic, biochemical, and clinical findings is essential to guide surgical decision-making and improve patient outcomes. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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