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11 pages, 327 KiB  
Article
Metabolic Mediation of the Association Between Hyperandrogenism and Paratubal Cysts in Polycystic Ovary Syndrome: A Structural Equation Modeling Approach
by Jin Kyung Baek, Chae Eun Hong, Hee Yon Kim and Bo Hyon Yun
J. Clin. Med. 2025, 14(15), 5545; https://doi.org/10.3390/jcm14155545 (registering DOI) - 6 Aug 2025
Abstract
Objectives: Paratubal cysts (PTCs) are embryological remnants and are potentially hormonally responsive. Since hyperandrogenism (HA) is representative of polycystic ovary syndrome (PCOS), we examined whether biochemical hyperandrogenism is associated with PTCs in women with PCOS and if body mass index (BMI) and [...] Read more.
Objectives: Paratubal cysts (PTCs) are embryological remnants and are potentially hormonally responsive. Since hyperandrogenism (HA) is representative of polycystic ovary syndrome (PCOS), we examined whether biochemical hyperandrogenism is associated with PTCs in women with PCOS and if body mass index (BMI) and insulin resistance (IR) mediate this association. Methods: This retrospective study included 577 women diagnosed with PCOS at a tertiary academic center from 2010 to 2018. Clinical data included age at diagnosis, BMI, and diagnoses of hypertension, non-alcoholic fatty liver disease, and metabolic syndrome. Laboratory measures included total testosterone, sex hormone-binding globulin, anti-Müllerian hormone, luteinizing hormone, fasting glucose, insulin, and triglycerides (TG). Derived indices included a free androgen index (FAI), homeostasis model assessment of insulin resistance (HOMA-IR), and fasting glucose-to-insulin ratio. PTCs were identified through imaging or surgical findings. Structural equation modeling (SEM) assessed direct and indirect relationships between FAI, BMI, HOMA-IR, and PTCs, while adjusting for diagnostic age. Results: PTCs were identified in 2.77% of participants. BMI, FAI, TG, and IR indices were significantly higher for women with PTCs than those without PTCs. SEM revealed significant indirect effects of FAI on PTCs via BMI and HOMA-IR. The direct effect was negative, resulting in a non-significant total effect. A sensitivity model using HOMA-IR as the predictor showed a significant direct effect on PTCs without mediation via FAI. Conclusions: Biochemical HA may influence PTC development in PCOS through metabolic pathways, establishing the need to consider metabolic context when evaluating adnexal cysts in hyperandrogenic women. Full article
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12 pages, 486 KiB  
Article
Efficacy and Safety of Dose-Dense Chemotherapy in Breast Cancer: Real Clinical Data and Literature Review
by Keiko Yanagihara, Masato Yoshida, Tamami Yamakawa, Sena Kato, Miki Tamura and Koji Nagata
Curr. Oncol. 2025, 32(8), 441; https://doi.org/10.3390/curroncol32080441 (registering DOI) - 6 Aug 2025
Abstract
Dose-dense chemotherapy shortens the interval between chemotherapy cycles and has shown improved outcomes in high-risk breast cancer patients. We retrospectively evaluated the efficacy and safety of dose-dense chemotherapy in 80 breast cancer patients treated at our hospital from 2020 to 2024. The regimen [...] Read more.
Dose-dense chemotherapy shortens the interval between chemotherapy cycles and has shown improved outcomes in high-risk breast cancer patients. We retrospectively evaluated the efficacy and safety of dose-dense chemotherapy in 80 breast cancer patients treated at our hospital from 2020 to 2024. The regimen included epirubicin and cyclophosphamide followed by paclitaxel or docetaxel, with pegfilgrastim support. The overall treatment completion rate was 82.5%. Of the 80 patients, 55 underwent neoadjuvant chemotherapy, and the pathological complete response rate was significantly higher in triple-negative breast cancer (59.1%) compared to that in luminal-type cancer (9.1%). Common adverse events included anemia, liver dysfunction, myalgia, and peripheral neuropathy. Febrile neutropenia occurred in 8.8% of patients, with some cases linked to pegfilgrastim body pod use, particularly in individuals with low subcutaneous fat. Notably, two patients developed pneumocystis pneumonia, potentially associated with steroid administration. Despite these toxicities, most were manageable and resolved after treatment. Our findings support the efficacy of dose-dense chemotherapy, particularly in triple-negative breast cancer, while highlighting the importance of individualized supportive care and vigilance regarding hematologic and infectious complications. Full article
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18 pages, 1528 KiB  
Review
Sex Differences in Colorectal Cancer: Epidemiology, Risk Factors, and Clinical Outcomes
by Sophia Tsokkou, Ioannis Konstantinidis, Menelaos Papakonstantinou, Paraskevi Chatzikomnitsa, Eftychia Liampou, Evdokia Toutziari, Dimitrios Giakoustidis, Petros Bangeas, Vasileios Papadopoulos and Alexandros Giakoustidis
J. Clin. Med. 2025, 14(15), 5539; https://doi.org/10.3390/jcm14155539 (registering DOI) - 6 Aug 2025
Abstract
Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a [...] Read more.
Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a higher incidence and mortality rate, with left-sided (distal) CRC predominating, while females are more frequently diagnosed with right-sided (proximal) tumors, which tend to be more aggressive and less responsive to conventional chemotherapy. Genetic disparities, including microsatellite instability and X-chromosome tumor suppressor genes, contribute to sex-specific differences in tumor progression and treatment response. Immune variations also influence disease outcomes, with females exhibiting stronger immune surveillance but higher exhaustion markers. Lifestyle factors such as body mass index (BMI), smoking, and hormonal influences further modulate CRC risk. While males are more vulnerable to obesity-related CRC, central obesity (waist-to-hip ratio) emerges as a stronger predictor in females. Additionally, smoking increases CRC risk differentially by tumor location. These findings underscore the importance of sex-specific approaches in CRC prevention, screening, and treatment, advocating for personalized medicine strategies tailored to gender-based biological and clinical distinctions. Full article
(This article belongs to the Special Issue Gastrointestinal Cancer: Outcomes and Therapeutic Management)
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19 pages, 1860 KiB  
Article
Multi-Objective Vibration Control of a Vehicle-Track-Bridge Coupled System Using Tuned Inerter Dampers Based on the FE-SEA Hybrid Method
by Xingxing Hu, Qingsong Feng, Min Yang and Jian Liu
Appl. Sci. 2025, 15(15), 8675; https://doi.org/10.3390/app15158675 (registering DOI) - 5 Aug 2025
Abstract
To address the adverse effects of Tuned Inertia Dampers (TIDs) on track slab vibrations while controlling high-frequency rail vibrations, a hybrid Finite Element-Statistical Energy Analysis (FE-SEA) method is developed for modeling the vehicle-track-bridge coupled system. Short-wavelength track irregularities are introduced as high-frequency excitation, [...] Read more.
To address the adverse effects of Tuned Inertia Dampers (TIDs) on track slab vibrations while controlling high-frequency rail vibrations, a hybrid Finite Element-Statistical Energy Analysis (FE-SEA) method is developed for modeling the vehicle-track-bridge coupled system. Short-wavelength track irregularities are introduced as high-frequency excitation, and the accuracy and efficiency of this method are validated by comparison with the traditional finite element method (FEM). A vibration control model for track-bridge structures incorporating TIDs is designed, and the effects of the TID’s inertance, stiffness, and damping coefficients on the vertical acceleration responses of the rail and track slab are investigated in detail. The study reveals that although TIDs effectively reduce rail vibrations, they may induce adverse effects on track slab vibrations. Using the vibration acceleration amplitudes of both the rail and track slab as dual control objectives, a multi-objective optimization model is established, and the TID’s optimal parameters are determined using a multi-objective genetic algorithm. The results show that the optimized TID parameters reduce rail acceleration amplitudes by 16.43% and improve the control efficiency by 12.45%, while also addressing the negative effects on track slab vibration. The track slab’s vibration acceleration is reduced by 5.47%, and the vertical displacement and acceleration of the vehicle body are reduced by 14.22% and 47.5%, respectively, thereby enhancing passenger comfort. This study provides new insights and theoretical guidance for vibration control analysis in vehicle-track-bridge coupled systems. Full article
22 pages, 1254 KiB  
Systematic Review
How Do the Psychological Functions of Eating Disorder Behaviours Compare with Self-Harm? A Systematic Qualitative Evidence Synthesis
by Faye Ambler, Andrew J. Hill, Thomas A. Willis, Benjamin Gregory, Samia Mujahid, Daniel Romeu and Cathy Brennan
Healthcare 2025, 13(15), 1914; https://doi.org/10.3390/healthcare13151914 - 5 Aug 2025
Abstract
Background: Eating disorders (EDs) and self-harm (SH) are both associated with distress, poor psychosocial functioning, and increased risk of mortality. Much of the literature discusses the complex interplay between SH and ED behaviours where co-occurrence is common. The onset of both is typically [...] Read more.
Background: Eating disorders (EDs) and self-harm (SH) are both associated with distress, poor psychosocial functioning, and increased risk of mortality. Much of the literature discusses the complex interplay between SH and ED behaviours where co-occurrence is common. The onset of both is typically seen during teenage years into early adulthood. A better understanding of the functions of these behaviours is needed to guide effective prevention and treatment, particularly during the crucial developmental years. An earlier review has explored the functions of self-harm, but an equivalent review for eating disorder behaviours does not appear to have been completed. Objectives: This evidence synthesis had two objectives. First, to identify and synthesise published first-hand accounts of the reasons why people engage in eating disorder behaviours with the view to develop a broad theoretical framework of functions. Second, to draw comparisons between the functions of eating disorder behaviours and self-harm. Methods: A qualitative evidence synthesis reporting first-hand accounts of the reasons for engaging in eating disorder behaviours. A ‘best fit’ framework synthesis, using the a priori framework from the review of self-harm functions, was undertaken with thematic analysis to categorise responses. Results: Following a systematic search and rigorous screening process, 144 studies were included in the final review. The most commonly reported functions of eating disorder behaviours were distress management (affect regulation) and interpersonal influence. This review identified significant overlap in functions between self-harm and eating disorder behaviours. Gender identity, responding to food insecurity, to delay growing up and responding to weight, shape, and body ideals were identified as functions more salient to eating disorder behaviours. Similarly, some self-harm functions were not identified in the eating disorder literature. These were experimenting, averting suicide, personal language, and exploring/maintaining boundaries. Conclusions: This evidence synthesis identified a prominent overlap between psychological functions of eating disorder behaviours and self-harm, specifically in relation to distress management (affect regulation). Despite clear overlap in certain areas, some functions were found to be distinct to each behaviour. The implications for delivering and adapting targeted interventions are discussed. Full article
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13 pages, 1667 KiB  
Article
Univariate and Multivariate Pattern Analysis Reveals the Effects of Negative Body Image at Fatness on Food-Related Inhibitory Control
by Zihan Xu, Yuchan Xu, Junyao Han, Lechang Sun, Junwei Lian, Zhifang Li, Yong Liu and Jia Zhao
Nutrients 2025, 17(15), 2555; https://doi.org/10.3390/nu17152555 - 5 Aug 2025
Abstract
Background/Objectives: Perceptions of obesity critically influence people’s eating behaviors and responses to food stimuli. However, few studies have investigated the impact of negative body perception on behavioral and neural responses to food stimuli. This study investigates how elevated body dissatisfaction modulates food-related inhibitory [...] Read more.
Background/Objectives: Perceptions of obesity critically influence people’s eating behaviors and responses to food stimuli. However, few studies have investigated the impact of negative body perception on behavioral and neural responses to food stimuli. This study investigates how elevated body dissatisfaction modulates food-related inhibitory control. Methods: Fifty-one participants comprising three cohorts—overweight/obese individuals (OO), normal-weight participants exhibiting high negative body image (HNN), and healthy controls—performed a food-specific inhibitory control task under EEG recording. Results: The results showed that the HNN cohort achieved superior no-go accuracy and enhanced inhibitory control compared to controls. An event-related potentials (ERPs) analysis revealed increased conflict detection (P200) for high-calorie foods and reduced conflict resolution (LPP) in the HNN group, similar to the overweight/obese group. A multivariate pattern analysis (MVPA) identified earlier neural discrimination in the HNN group, suggesting more efficient inhibitory processing. Conclusions: These findings underscore negative body perception as a critical modulator of food-related cognitive control mechanisms. Full article
(This article belongs to the Section Nutrition and Obesity)
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27 pages, 2559 KiB  
Review
Virgin Coconut Oil and Its Lauric Acid, Between Anticancer Activity and Modulation of Chemotherapy Toxicity: A Review
by Debalina Bose, Adetayo Olorunlana, Rania Abdel-Latif, Ademola C. Famurewa and Eman M. Othman
J. Xenobiot. 2025, 15(4), 126; https://doi.org/10.3390/jox15040126 - 5 Aug 2025
Abstract
Virgin coconut oil (VCO) has emerged as a functional food oil with considerable health benefits and wide applications in the food, pharmaceutical, and cosmetic industries due to its resident bioactive compounds, including lauric acid (LA). LA is the most abundant saturated medium-chain fatty [...] Read more.
Virgin coconut oil (VCO) has emerged as a functional food oil with considerable health benefits and wide applications in the food, pharmaceutical, and cosmetic industries due to its resident bioactive compounds, including lauric acid (LA). LA is the most abundant saturated medium-chain fatty acid in VCO and has been associated with several pharmacological activities. The literatures show the pharmacological effects of VCO and LA on chronic pathologies, infectious diseases, and metabolic disorders. A robust body of evidence shows that LA and other phenolic compounds are responsible for the VCO protection against toxicities and pharmacological efficacies. This review elucidates the anticancer mechanisms of VCO/LA and their modulation of the chemotherapy-induced side effect toxicity. VCO, LA, and their nanomaterial/encapsulated derivatives promote ROS generation, antiproliferation, apoptosis, cell cycle arrest, the inhibition of metastasis, and the modulation of cancer-related signaling pathways for cancer cell death in vivo and in vitro. VCO mitigates oxidative inflammation and apoptosis to block the underlying mechanisms of the side effect toxicity of chemotherapy. However, the possible beneficial effect of LA on the toxicity of chemotherapy is currently unknown. The available evidence emphasizes the anticancer effect and mechanism of VCO and LA, and the VCO potential to combat adverse side effects of chemotherapy. Thus, VCO and LA are potential adjuvant therapeutic agents in the management of various cancers. Nevertheless, future studies should be targeted at elucidating cancer-related molecular mechanisms to bridge the gap in knowledge. Full article
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16 pages, 5104 KiB  
Article
Integrating OpenPose for Proactive Human–Robot Interaction Through Upper-Body Pose Recognition
by Shih-Huan Tseng, Jhih-Ciang Chiang, Cheng-En Shiue and Hsiu-Ping Yueh
Electronics 2025, 14(15), 3112; https://doi.org/10.3390/electronics14153112 - 5 Aug 2025
Abstract
This paper introduces a novel system that utilizes OpenPose for skeleton estimation to enable a tabletop robot to interact with humans proactively. By accurately recognizing upper-body poses based on the skeleton information, the robot autonomously approaches individuals and initiates conversations. The contributions of [...] Read more.
This paper introduces a novel system that utilizes OpenPose for skeleton estimation to enable a tabletop robot to interact with humans proactively. By accurately recognizing upper-body poses based on the skeleton information, the robot autonomously approaches individuals and initiates conversations. The contributions of this paper can be summarized into three main features. Firstly, we conducted a comprehensive data collection process, capturing five different table-front poses: looking down, looking at the screen, looking at the robot, resting the head on hands, and stretching both hands. These poses were selected to represent common interaction scenarios. Secondly, we designed the robot’s dialog content and movement patterns to correspond with the identified table-front poses. By aligning the robot’s responses with the specific pose, we aimed to create a more engaging and intuitive interaction experience for users. Finally, we performed an extensive evaluation by exploring the performance of three classification models—non-linear Support Vector Machine (SVM), Artificial Neural Network (ANN), and convolutional neural network (CNN)—for accurately recognizing table-front poses. We used an Asus Zenbo Junior robot to acquire images and leveraged OpenPose to extract 12 upper-body skeleton points as input for training the classification models. The experimental results indicate that the ANN model outperformed the other models, demonstrating its effectiveness in pose recognition. Overall, the proposed system not only showcases the potential of utilizing OpenPose for proactive human–robot interaction but also demonstrates its real-world applicability. By combining advanced pose recognition techniques with carefully designed dialog and movement patterns, the tabletop robot successfully engages with humans in a proactive manner. Full article
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25 pages, 1238 KiB  
Article
Myokine Circulating Levels in Postmenopausal Women with Overweight or Obesity: Effects of Resistance Training and/or DHA-Rich n-3 PUFA Supplementation
by Alejandro Martínez-Gayo, Elisa Félix-Soriano, Javier Ibáñez-Santos, Marisol García-Unciti, Pedro González-Muniesa, María J. Moreno-Aliaga and on behalf of OBELEX Project
Nutrients 2025, 17(15), 2553; https://doi.org/10.3390/nu17152553 - 5 Aug 2025
Abstract
Background: Menopause increases the risk of cardiovascular diseases (CVD) accompanied by a decline in muscle function. Myokines, released by skeletal muscle, could play a significant role in cardiovascular health. Objectives and Methods: This study aimed to investigate the changes induced by a 16-week [...] Read more.
Background: Menopause increases the risk of cardiovascular diseases (CVD) accompanied by a decline in muscle function. Myokines, released by skeletal muscle, could play a significant role in cardiovascular health. Objectives and Methods: This study aimed to investigate the changes induced by a 16-week resistance training (RT) program and/or the docosahexaenoic acid (DHA)-rich n-3 PUFA supplementation on myokine and cytokine circulating levels and to study their associations with parameters of body composition, muscle function, and glucose and lipid serum markers in postmenopausal women with overweight/obesity. Results: At baseline, interleukin-6 (IL-6) levels were positively correlated with body fat and with tumor necrosis factor-alpha (TNF-α) levels and negatively associated with meterorin-like (METRNL) levels. Moreover, METRNL was inversely associated with insulin levels and with HOMA-IR. After the intervention, muscle quality improved with either treatment but more notably in response to RT. N-3 supplementation caused significant improvements in cardiometabolic health markers. TNF-α decreased in all experimental groups. Myostatin levels decreased in the RT and in the n-3 groups, and IL-6 increased in the n-3+RT group. Lastly, no interactions between treatments were observed. Conclusions: In postmenopausal women with overweight or obesity, RT could help improve skeletal muscle function, while DHA-rich n-3 supplementation might decrease CVD risk and might potentially improve muscle function. The modulation of myokine levels could be underlying some of the effects of DHA or RT; however, further research is necessary. Full article
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14 pages, 551 KiB  
Article
Responses of Broiler Breeder Hens to Dietary Digestible Lysine, Methionine+Cystine, and Threonine
by Michele B. de Lima, Nilva K. Sakomura, Cléber F. S. Oliveira, Rita B. Vieira, Jaqueline A. Pavanini and Edney P. da Silva
Agriculture 2025, 15(15), 1685; https://doi.org/10.3390/agriculture15151685 - 4 Aug 2025
Abstract
To evaluate the response of broiler breeder hens submitted to different amino acid intakes of methionine+cystine, lysine, and threonine, and to determine the coefficients for egg output and body weight for maintenance. Three studies were performed using 160 broiler breeder hens housed individually [...] Read more.
To evaluate the response of broiler breeder hens submitted to different amino acid intakes of methionine+cystine, lysine, and threonine, and to determine the coefficients for egg output and body weight for maintenance. Three studies were performed using 160 broiler breeder hens housed individually in metabolic cages. A summit diet and a nitrogen-free diet were formulated. The levels ranged from 1.79 to 7.13, 2.49 to 8.3, and 2.04 to 6.79 g/kg of methionine+cystine, lysine, and threonine, respectively. The variables measured were feed intake, amino acid intake, rate of lay, egg weight, and egg output. The broken line model was used to evaluate the responses. It was verified that higher values of the rate of lay, egg weight, and egg output were observed for the higher concentrations of amino acids studied. A significant difference was observed for the variables rate of lay, egg weight, egg output, and body weight (p < 0.05) for the three amino acids evaluated. The amount of each amino acid required to produce one gram per egg was estimated at 12.4 mg, 14.5 mg, and 11.2 mg for methionine+cystine, lysine, and threonine, respectively. The values estimated by coefficient b that represent the amino acid for maintenance requirement were methionine+cystine, lysine, and threonine of 30.2, 32.2, and 42.4 mg/kg BW, respectively. The coefficients may be used to design additional models to study requirements nutrition in broiler breeders, allowing a better understanding of how these birds respond to different dietary amino acids. Full article
(This article belongs to the Section Farm Animal Production)
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31 pages, 3455 KiB  
Review
Recent Advances in Nanoparticle and Nanocomposite-Based Photodynamic Therapy for Cervical Cancer: A Review
by Dorota Bartusik-Aebisher, Mohammad A. Saad, Agnieszka Przygórzewska and David Aebisher
Cancers 2025, 17(15), 2572; https://doi.org/10.3390/cancers17152572 - 4 Aug 2025
Abstract
Cervical cancer represents a significant global health challenge. Photodynamic therapy (PDT) appears to be a promising, minimally invasive alternative to standard treatments. However, the clinical efficacy of PDT is sometimes limited by the low solubility and aggregation of photosensitizers, their non-selective distribution in [...] Read more.
Cervical cancer represents a significant global health challenge. Photodynamic therapy (PDT) appears to be a promising, minimally invasive alternative to standard treatments. However, the clinical efficacy of PDT is sometimes limited by the low solubility and aggregation of photosensitizers, their non-selective distribution in the body, hypoxia in the tumor microenvironment, and limited light penetration. Recent advances in nanoparticle and nanocomposite platforms have addressed these challenges by integrating multiple functional components into a single delivery system. By encapsulating or conjugating photosensitizers in biodegradable matrices, such as mesoporous silica, organometallic structures and core–shell construct nanocarriers increase stability in water and extend circulation time, enabling both passive and active targeting through ligand decoration. Up-conversion and dual-wavelength responsive cores facilitate deep light conversion in tissues, while simultaneous delivery of hypoxia-modulating agents alleviates oxygen deprivation to sustain reactive oxygen species generation. Controllable “motor-cargo” constructs and surface modifications improve intratumoral diffusion, while aggregation-induced emission dyes and plasmonic elements support real-time imaging and quantitative monitoring of therapeutic response. Together, these multifunctional nanosystems have demonstrated potent cytotoxicity in vitro and significant tumor suppression in vivo in mouse models of cervical cancer. Combining targeted delivery, controlled release, hypoxia mitigation, and image guidance, engineered nanoparticles provide a versatile and powerful platform to overcome the current limitations of PDT and pave the way toward more effective, patient-specific treatments for cervical malignancies. Our review of the literature summarizes studies on nanoparticles and nanocomposites used in PDT monotherapy for cervical cancer, published between 2023 and July 2025. Full article
(This article belongs to the Section Cancer Therapy)
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14 pages, 508 KiB  
Article
The Cytotoxic Potential of Humanized γδ T Cells Against Human Cancer Cell Lines in In Vitro
by Husheem Michael, Abigail T. Lenihan, Mikaela M. Vallas, Gene W. Weng, Jonathan Barber, Wei He, Ellen Chen, Paul Sheiffele and Wei Weng
Cells 2025, 14(15), 1197; https://doi.org/10.3390/cells14151197 - 4 Aug 2025
Abstract
Cancer is a major global health issue, with rising incidence rates highlighting the urgent need for more effective treatments. Despite advances in cancer therapy, challenges such as adverse effects and limitations of existing treatments remain. Immunotherapy, which harnesses the body’s immune system to [...] Read more.
Cancer is a major global health issue, with rising incidence rates highlighting the urgent need for more effective treatments. Despite advances in cancer therapy, challenges such as adverse effects and limitations of existing treatments remain. Immunotherapy, which harnesses the body’s immune system to target cancer cells, offers promising solutions. Gamma delta (γδ) T cells are noteworthy due to their potent ability to kill various cancer cells without needing conventional antigen presentation. Recent studies have focused on the role of γδ T cells in α-galactosylceramide (α-GalCer)-mediated immunity, opening new possibilities for cancer immunotherapy. We engineered humanized T cell receptor (HuTCR)-T1 γδ mice by replacing mouse sequences with human counterparts. This study investigates the cytotoxic activity of humanized γδ T cells against several human cancer cell lines (A431, HT-29, K562, and Daudi) in vitro, aiming to elucidate mechanisms underlying their anticancer efficacy. Human cancer cells were co-cultured with humanized γδ T cells, with and without α-GalCer, for 24 h. The humanized γδ T cells showed enhanced cytotoxicity across all tested cancer cell lines compared to wild-type γδ T cells. Additionally, γδ T cells from HuTCR-T1 mice exhibited higher levels of anticancer cytokines (IFN-γ, TNF-α, and IL-17) and Granzyme B, indicating their potential as potent mediators of anticancer immune responses. Blocking γδ T cells’ cytotoxicity confirmed their γδ-mediated function. These findings represent a significant step in preclinical development of γδ T cell-based cancer immunotherapies, providing insights into their mechanisms of action, optimization of therapeutic strategies, and identification of predictive biomarkers for clinical application. Full article
(This article belongs to the Special Issue Unconventional T Cells in Health and Disease)
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16 pages, 2235 KiB  
Article
Plasma Lysophosphatidylcholine Levels Correlate with Prognosis and Immunotherapy Response in Squamous Cell Carcinoma
by Tomoyuki Iwasaki, Hidekazu Shirota, Eiji Hishinuma, Shinpei Kawaoka, Naomi Matsukawa, Yuki Kasahara, Kota Ouchi, Hiroo Imai, Ken Saijo, Keigo Komine, Masanobu Takahashi, Chikashi Ishioka, Seizo Koshiba and Hisato Kawakami
Int. J. Mol. Sci. 2025, 26(15), 7528; https://doi.org/10.3390/ijms26157528 - 4 Aug 2025
Abstract
Cancer is a systemic disease rather than a localized pathology and is characterized by widespread effects, including whole-body exhaustion and chronic inflammation. A thorough understanding of cancer pathophysiology requires a systemic approach that accounts for the complex interactions between cancer cells and host [...] Read more.
Cancer is a systemic disease rather than a localized pathology and is characterized by widespread effects, including whole-body exhaustion and chronic inflammation. A thorough understanding of cancer pathophysiology requires a systemic approach that accounts for the complex interactions between cancer cells and host tissues. To explore these dynamics, we employed a comprehensive metabolomic analysis of plasma samples from patients with either esophageal or head and neck squamous cell carcinoma (SCC). Plasma samples from 149 patients were metabolically profiled and correlated with clinical data. Among the metabolites identified, lysophosphatidylcholine (LPC) emerged as the sole biomarker strongly correlated with prognosis. A significant reduction in plasma LPC levels was linked to poorer overall survival. Plasma LPC levels demonstrated minimal correlation with patient-specific factors, such as tumor size and general condition, but showed significant association with the response to immune checkpoint inhibitor therapy. Proteomic and cytokine analyses revealed that low plasma LPC levels reflected systemic chronic inflammation, characterized by high levels of inflammatory proteins, the cytokines interleukin-6 and tumor necrosis factor-α, and coagulation-related proteins. These findings indicate that plasma LPC levels may be used as reliable biomarkers for predicting prognosis and evaluating the efficacy of immunotherapy in patients with SCC. Full article
(This article belongs to the Special Issue Molecular Diagnostics and Genomics of Tumors)
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15 pages, 798 KiB  
Review
Angiotensin II and Atherosclerosis: A New Cardiovascular Risk Factor Beyond Hypertension
by Nicola Morat, Giovanni Civieri, Matteo Spezia, Mirko Menegolo, Giacomo Bernava, Sabino Iliceto, Laura Iop and Francesco Tona
Int. J. Mol. Sci. 2025, 26(15), 7527; https://doi.org/10.3390/ijms26157527 - 4 Aug 2025
Abstract
The pivotal role of angiotensin II (AngII) in cardiovascular disease has been firmly established, as evidenced by a robust body of literature and the broad clinical application of AngII-inhibiting therapies. AngII type 1 receptor is the primary mediator of AngII action, and its [...] Read more.
The pivotal role of angiotensin II (AngII) in cardiovascular disease has been firmly established, as evidenced by a robust body of literature and the broad clinical application of AngII-inhibiting therapies. AngII type 1 receptor is the primary mediator of AngII action, and its activation initiates a multitude of cellular responses that contribute to the development of hypertension, structural changes in the heart and vasculature, and damage to target organs. This review examines AngII from a different perspective, exploring the link between the renin–angiotensin–aldosterone system and cardiovascular risk beyond hypertension, with particular emphasis on atherosclerosis development and progression. Full article
(This article belongs to the Special Issue New Cardiovascular Risk Factors: 2nd Edition)
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42 pages, 1407 KiB  
Review
Antioxidants and Reactive Oxygen Species: Shaping Human Health and Disease Outcomes
by Charles F. Manful, Eric Fordjour, Dasinaa Subramaniam, Albert A. Sey, Lord Abbey and Raymond Thomas
Int. J. Mol. Sci. 2025, 26(15), 7520; https://doi.org/10.3390/ijms26157520 - 4 Aug 2025
Abstract
Reactive molecules, including oxygen and nitrogen species, serve dual roles in human physiology. While they function as essential signaling molecules under normal physiological conditions, they contribute to cellular dysfunction and damage when produced in excess by normal metabolism or in response to stressors. [...] Read more.
Reactive molecules, including oxygen and nitrogen species, serve dual roles in human physiology. While they function as essential signaling molecules under normal physiological conditions, they contribute to cellular dysfunction and damage when produced in excess by normal metabolism or in response to stressors. Oxidative/nitrosative stress is a pathological state, resulting from the overproduction of reactive species exceeding the antioxidant capacity of the body, which is implicated in several chronic human diseases. Antioxidant therapies aimed at restoring redox balance and preventing oxidative/nitrosative stress have demonstrated efficacy in preclinical models. However, their clinical applications have met with inconsistent success owing to efficacy, safety, and bioavailability concerns. This summative review analyzes the role of reactive species in human pathophysiology, the mechanisms of action of antioxidant protection, and the challenges that hinder their translation into effective clinical therapies in order to evaluate potential emerging strategies such as targeted delivery systems, precision medicine, and synergistic therapeutic approaches, among others, to overcome current limitations. By integrating recent advances, this review highlights the value of targeting reactive species in the prevention and management of chronic diseases. Full article
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