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17 pages, 4768 KiB  
Article
New Functional Food for the Treatment of Gastric Ulcer Based on Bioadhesive Microparticles Containing Sage Extract: Anti-Ulcerogenic, Anti-Helicobacter pylori, and H+/K+-ATPase-Inhibiting Activity Enhancement
by Yacine Nait Bachir, Ryma Nait Bachir, Meriem Medjkane, Nouara Boudjema and Roberta Foligni
Foods 2025, 14(15), 2757; https://doi.org/10.3390/foods14152757 (registering DOI) - 7 Aug 2025
Abstract
Salvia officinalis is an aromatic plant of Mediterranean origin traditionally used to treat inflammatory, cardiovascular, endocrine, and digestive diseases. In this work, the ability of the Salvia officinalis extract in the treatment of gastric ulcers was evaluated, and an innovative administration system was [...] Read more.
Salvia officinalis is an aromatic plant of Mediterranean origin traditionally used to treat inflammatory, cardiovascular, endocrine, and digestive diseases. In this work, the ability of the Salvia officinalis extract in the treatment of gastric ulcers was evaluated, and an innovative administration system was proposed to increase the therapeutic effect of this plant. Salvia officinalis ethanolic extract was prepared and analyzed by HPLC/UV-DAD and encapsulated in a matrix based on gelatin and pectin using an emulsion–coacervation process. The prepared microcapsules were analyzed by laser particle size, optical microscopy, in vitro dissolution kinetics, and ex vivo bioadhesion. In order to determine the action mechanism of Salvia officinalis extract, in the treatment of gastric ulcer, the in vivo anti-ulcerogenic activity in rats, using the ulcer model induced by ethanol; the in vivo anti-Helicobacter pylori activity; and in vitro inhibitory activity of H+/K+-ATPase were carried out. These three biological activities were evaluated for ethanolic extract and microcapsules to determine the effect of formulation on biological activities. Ethanolic extract of Salvia officinalis was mainly composed of polyphenols (chlorogenic acid 7.43%, rutin 21.74%, rosmarinic acid 5.88%, and quercitrin 14.39%). Microencapsulation of this extract allowed us to obtain microcapsules of 104.2 ± 7.5 µm in diameter, an encapsulation rate of 96.57 ± 3.05%, and adequate bioadhesion. The kinetics of in vitro dissolution of the extract increase significantly after its microencapsulation. Percentages of ulcer inhibition for 100 mg/kg of extract increase from 71.71 ± 2.43% to 89.67 ± 2.54% after microencapsulation. In vitro H+/K+-ATPase-inhibiting activity resulted in an IC50 of 86.08 ± 8.69 µM/h/mg protein for free extract and 57.43 ± 5.78 µM/h/mg protein for encapsulated extract. Anti-Helicobacter pylori activity showed a similar Minimum Inhibitory Concentration (MIC) of 50 µg/mL for the extract and microcapsules. Salvia officinalis ethanolic extract has a significant efficacy for the treatment of gastric ulcer; its mechanism of action is based on its gastroprotective effect, anti-Helicobacter pylori, and H+/K+-ATPase inhibitor. Moreover, the microencapsulation of this extract increases its gastroprotective and H+/K+-ATPase-inhibiting activities significantly. Full article
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19 pages, 1632 KiB  
Guidelines
Multidisciplinary Practical Guidance for Implementing Adjuvant CDK4/6 Inhibitors for Patients with HR-Positive, HER2-Negative Early Breast Cancer in Canada
by Katarzyna J. Jerzak, Sandeep Sehdev, Jean-François Boileau, Christine Brezden-Masley, Nadia Califaretti, Scott Edwards, Jenn Gordon, Jan-Willem Henning, Nathalie LeVasseur and Cindy Railton
Curr. Oncol. 2025, 32(8), 444; https://doi.org/10.3390/curroncol32080444 - 7 Aug 2025
Abstract
Cyclin-dependent kinase (CDK)4/6 inhibitors have become a key component of adjuvant treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer who are at high risk of recurrence. The addition of abemaciclib and ribociclib to standard [...] Read more.
Cyclin-dependent kinase (CDK)4/6 inhibitors have become a key component of adjuvant treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer who are at high risk of recurrence. The addition of abemaciclib and ribociclib to standard endocrine therapy has demonstrated clinically meaningful improvements in invasive disease-free survival, supported by the monarchE and NATALEE trials, respectively. With expansion of patient eligibility for CDK4/6 inhibitors, multidisciplinary coordination among medical oncologists, surgeons, nurses, pharmacists, and other health care providers is critical to optimizing patient identification, monitoring, and management of adverse events. This expert guidance document provides practical recommendations for implementing adjuvant CDK4/6 inhibitor therapy in routine clinical practice, incorporating insights from multiple specialties and with patient advocacy representation. Key considerations include patient selection based on clinical trial data, treatment duration, dosing schedules, adverse event profiles, monitoring requirements, drug–drug interactions, and patient-specific factors such as tolerability, cost, and quality of life. This guidance aims to support Canadian clinicians in effectively integrating CDK4/6 inhibitors into clinical practice, ensuring optimal patient outcomes through a multidisciplinary and patient-centric approach. Full article
(This article belongs to the Section Breast Cancer)
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28 pages, 3469 KiB  
Review
Prostate Cancer Treatments and Their Effects on Male Fertility: Mechanisms and Mitigation Strategies
by Aris Kaltsas, Nikolaos Razos, Zisis Kratiras, Dimitrios Deligiannis, Marios Stavropoulos, Konstantinos Adamos, Athanasios Zachariou, Fotios Dimitriadis, Nikolaos Sofikitis and Michael Chrisofos
J. Pers. Med. 2025, 15(8), 360; https://doi.org/10.3390/jpm15080360 - 7 Aug 2025
Abstract
Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating [...] Read more.
Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating a growing cohort of younger survivors for whom post-treatment quality of life—notably reproductive function—is paramount. Curative treatments such as radical prostatectomy, pelvic radiotherapy, androgen-deprivation therapy (ADT), and chemotherapy often cause irreversible infertility via multiple mechanisms, including surgical disruption of the ejaculatory tract, endocrine suppression of spermatogenesis, direct gonadotoxic injury to the testes, and oxidative sperm DNA damage. Despite these risks, fertility preservation is frequently overlooked in pre-treatment counseling, leaving many patients unaware of their options. This narrative review synthesizes current evidence on how PCa therapies impact male fertility, elucidates the molecular and physiological mechanisms of iatrogenic infertility, and evaluates both established and emerging strategies for fertility preservation and restoration. Key interventions covered include sperm cryopreservation, microsurgical testicular sperm extraction (TESE), and assisted reproductive technologies (ART). Psychosocial factors influencing decision-making, novel biomarkers predictive of post-treatment spermatogenic recovery, and long-term offspring outcomes are also examined. The review underscores the urgent need for timely, multidisciplinary fertility consultation as a routine component of PCa care. As PCa increasingly affects men in their reproductive years, proactively integrating preservation into standard oncologic practice should become a standard survivorship priority. Full article
(This article belongs to the Special Issue Clinical Advances in Male Genitourinary and Sexual Health)
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24 pages, 330 KiB  
Review
Collaboration Between Endocrinologists and Dentists in the Care of Patients with Acromegaly—A Narrative Review
by Beata Wiśniewska, Kosma Piekarski, Sandra Spychała, Ewelina Golusińska-Kardach, Maria Stelmachowska-Banaś and Marzena Wyganowska
J. Clin. Med. 2025, 14(15), 5511; https://doi.org/10.3390/jcm14155511 - 5 Aug 2025
Abstract
Acromegaly is caused by an excessive secretion of growth hormone and the secondary elevation of IGF-1 levels, leading to progressive changes in multiple body systems, including the craniofacial region and oral cavity. Dental manifestations such as mandibular overgrowth, macroglossia, malocclusion, periodontal disease, and [...] Read more.
Acromegaly is caused by an excessive secretion of growth hormone and the secondary elevation of IGF-1 levels, leading to progressive changes in multiple body systems, including the craniofacial region and oral cavity. Dental manifestations such as mandibular overgrowth, macroglossia, malocclusion, periodontal disease, and prosthetic difficulties represent not only a clinical component of the disease but also a significant therapeutic and diagnostic challenge. The aim of this review is to present the current state of knowledge on the relationship between acromegaly and oral health and to analyze the role of interdisciplinary collaboration between endocrinologists and dentists in patient care. For this narrative review, a literature search was conducted in the PubMed, Scopus, and Web of Science databases covering the period from 2000 to 2025. Sixty-two peer-reviewed publications meeting the methodological and thematic criteria were included in the analysis, including original studies, meta-analyses, systematic reviews, and case reports. The results indicate significant correlations between disease activity and the severity of periodontal and microbiological changes, while effective endocrine treatment only results in the partial regression of morphological changes. Particular attention was given to the role of the dentist in recognizing the early symptoms of the disease, planning prosthetic and surgical treatment, and monitoring therapy-related complications. Interdisciplinary collaboration models, including integrated clinics and co-managed care, were also described as optimal systemic solutions for improving treatment quality. The conclusion drawn from the analysis are as follows: there is a need for the permanent integration of dentistry into the standard of interdisciplinary care for patients with acromegaly, in both diagnostic and therapeutic dimensions. Increasing awareness among dentists and developing integrated collaboration models may reduce the time to diagnosis, improve patients’ quality of life, and enable the more effective management of craniofacial complications in the course of this rare disease. Full article
(This article belongs to the Section Endocrinology & Metabolism)
13 pages, 2643 KiB  
Review
Primary Hyperparathyroidism: 18F-Fluorocholine PET/CT vs. 4D-CT for Parathyroid Identification: Toward a Comprehensive Diagnostic Framework—An Updated Review and Recommendations
by Gregorio Scerrino, Nunzia Cinzia Paladino, Giuseppa Graceffa, Giuseppina Melfa, Giuseppina Orlando, Renato Di Vuolo, Chiara Lo Cicero, Alessandra Murabito, Stefano Radellini, Pierina Richiusa and Antonio Lo Casto
J. Clin. Med. 2025, 14(15), 5468; https://doi.org/10.3390/jcm14155468 - 4 Aug 2025
Viewed by 90
Abstract
Introduction: Primary hyperparathyroidism (pHPT) is an endocrine disorder characterized by excessive parathyroid hormone production, typically due to adenomas, hyperplasia, or carcinoma. Preoperative imaging plays a critical role in guiding surgical planning, particularly in selecting patients for minimally invasive procedures. While first-line imaging [...] Read more.
Introduction: Primary hyperparathyroidism (pHPT) is an endocrine disorder characterized by excessive parathyroid hormone production, typically due to adenomas, hyperplasia, or carcinoma. Preoperative imaging plays a critical role in guiding surgical planning, particularly in selecting patients for minimally invasive procedures. While first-line imaging techniques, such as ultrasound and 99mTc-sestamibi scintigraphy, are standard, advanced second-line imaging modalities like 18F-fluorocholine PET/CT (FCH-PET) and four-dimensional computed tomography (4D-CT) have emerged as valuable tools when initial diagnostics are inconclusive. Methods: This article provides an updated review and recommendations of the role of these advanced imaging techniques in localizing parathyroid adenomas. Results: FCH-PET has shown exceptional sensitivity (94% per patient, 96% per lesion) and is particularly useful in detecting small or ectopic adenomas. Despite its higher sensitivity, it can yield false positives, particularly in the presence of thyroid disease. On the other hand, 4D-CT offers detailed anatomical imaging, aiding in the identification of parathyroids in challenging cases, including recurrent disease and ectopic glands. Studies suggest that FCH-PET and 4D-CT exhibit similar diagnostic performance and could be complementary in preoperative planning of most difficult situations. Conclusions: This article also emphasizes a multimodal approach, where initial imaging is followed by advanced techniques only in cases of uncertainty. Although 18F-fluorocholine PET/CT is favored as a second-line option, 4D-CT remains invaluable for its high spatial resolution and ability to guide surgery in complex cases. Despite limitations in evidence, these imaging modalities significantly enhance the accuracy of parathyroid localization, contributing to more targeted and minimally invasive surgery. Full article
(This article belongs to the Section General Surgery)
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19 pages, 1016 KiB  
Article
Genetic Associations of ITGB3, FGG, GP1BA, PECAM1, and PEAR1 Polymorphisms and the Platelet Activation Pathway with Recurrent Pregnancy Loss in the Korean Population
by Eun Ju Ko, Eun Hee Ahn, Hyeon Woo Park, Jae Hyun Lee, Da Hwan Kim, Young Ran Kim, Ji Hyang Kim and Nam Keun Kim
Int. J. Mol. Sci. 2025, 26(15), 7505; https://doi.org/10.3390/ijms26157505 - 3 Aug 2025
Viewed by 239
Abstract
Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women [...] Read more.
Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women may experience two or more consecutive pregnancy losses. Previous studies have investigated risk factors for RPL, including maternal age, uterine pathology, genetic anomalies, infectious agents, endocrine disorders, thrombophilia, and immune dysfunction. However, RPL is a disease caused by a complex interaction of genetic factors, environmental factors (e.g., diet, lifestyle, and stress), epigenetic factors, and the immune system. In addition, due to the lack of research on genetics research related to RPL, the etiology remains unclear in up to 50% of cases. Platelets play a critical role in pregnancy maintenance. This study examined the associations of platelet receptor and ligand gene variants, including integrin subunit beta 3 (ITGB3) rs2317676 A > G, rs3809865 A > T; fibrinogen gamma chain (FGG) rs1049636 T > C, rs2066865 T > C; glycoprotein 1b subunit alpha (GP1BA) rs2243093 T > C, rs6065 C > T; platelet endothelial cell adhesion molecule 1 (PECAM1) rs2812 C > T; and platelet endothelial aggregation receptor 1 (PEAR1) rs822442 C > A, rs12137505 G > A, with RPL prevalence. In total, 389 RPL patients and 375 healthy controls (all Korean women) were enrolled. Genotyping of each single nucleotide polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism and the TaqMan genotyping assay. All samples were collected with approval from the Institutional Review Board at Bundang CHA Medical Center. The ITGB3 rs3809865 A > T genotype was strongly associated with RPL prevalence (pregnancy loss [PL] ≥ 2: adjusted odds ratio [AOR] = 2.505, 95% confidence interval [CI] = 1.262–4.969, p = 0.009; PL ≥ 3: AOR = 3.255, 95% CI = 1.551–6.830, p = 0.002; PL ≥ 4: AOR = 3.613, 95% CI = 1.403–9.307, p = 0.008). The FGG rs1049636 T > C polymorphism was associated with a decreased risk in women who had three or more pregnancy losses (PL ≥ 3: AOR = 0.673, 95% CI = 0.460–0.987, p = 0.043; PL ≥ 4: AOR = 0.556, 95% CI = 0.310–0.997, p = 0.049). These findings indicate significant associations of the ITGB3 rs3809865 A > T and FGG rs1049636 T > C polymorphisms with RPL, suggesting that platelet function influences RPL in Korean women. Full article
(This article belongs to the Special Issue Molecular Research in Gynecological Diseases—2nd Edition)
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22 pages, 3527 KiB  
Review
Applications of Organoids and Spheroids in Anaplastic and Papillary Thyroid Cancer Research: A Comprehensive Review
by Deepak Gulwani, Neha Singh, Manisha Gupta, Ridhima Goel and Thoudam Debraj Singh
Organoids 2025, 4(3), 18; https://doi.org/10.3390/organoids4030018 - 1 Aug 2025
Viewed by 129
Abstract
Organoid and spheroid technologies have rapidly become pivotal in thyroid cancer research, offering models that are more physiologically relevant than traditional two-dimensional culture. In the study of papillary and anaplastic thyroid carcinomas, two subtypes that differ both histologically and clinically, three-dimensional (3D) models [...] Read more.
Organoid and spheroid technologies have rapidly become pivotal in thyroid cancer research, offering models that are more physiologically relevant than traditional two-dimensional culture. In the study of papillary and anaplastic thyroid carcinomas, two subtypes that differ both histologically and clinically, three-dimensional (3D) models offer unparalleled insights into tumor biology, therapeutic vulnerabilities, and resistance mechanisms. These models maintain essential tumor characteristics such as cellular diversity, spatial structure, and interactions with the microenvironment, making them extremely valuable for disease modeling and drug testing. This review emphasizes recent progress in the development and use of thyroid cancer organoids and spheroids, focusing on their role in replicating disease features, evaluating targeted therapies, and investigating epithelial–mesenchymal transition (EMT), cancer stem cell behavior, and treatment resistance. Patient-derived organoids have shown potential in capturing individualized drug responses, supporting precision oncology strategies for both differentiated and aggressive subtypes. Additionally, new platforms, such as thyroid organoid-on-a-chip systems, provide dynamic, high-fidelity models for functional studies and assessments of endocrine disruption. Despite ongoing challenges, such as standardization, limited inclusion of immune and stromal components, and culture reproducibility, advancements in microfluidics, biomaterials, and machine learning have enhanced the clinical and translational potential of these systems. Organoids and spheroids are expected to become essential in the future of thyroid cancer research, particularly in bridging the gap between laboratory discoveries and patient-focused therapies. Full article
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25 pages, 7131 KiB  
Article
Spatiotemporal Patterns of Non-Communicable Disease Mortality in the Metropolitan Area of the Valley of Mexico, 2000–2019
by Constantino González-Salazar, Kathia Gasca-Gómez and Omar Cordero-Saldierna
Diseases 2025, 13(8), 241; https://doi.org/10.3390/diseases13080241 - 1 Aug 2025
Viewed by 324
Abstract
Background: Non-communicable diseases (NCDs) are a leading cause of mortality globally, contributing significantly to the burden on healthcare systems. Understanding the spatiotemporal patterns of NCD mortality is crucial for identifying vulnerable populations and regions at high risk. Objectives: Here, we evaluated the spatiotemporal [...] Read more.
Background: Non-communicable diseases (NCDs) are a leading cause of mortality globally, contributing significantly to the burden on healthcare systems. Understanding the spatiotemporal patterns of NCD mortality is crucial for identifying vulnerable populations and regions at high risk. Objectives: Here, we evaluated the spatiotemporal patterns of NCD mortality in the Metropolitan Area of the Valley of Mexico (MAVM) from 2000 to 2019 for five International Classification of Diseases chapters (4, 5, 6, 9, and 10) at two spatial scales: the municipal level and metropolitan region. Methods: Mortality rates were calculated for the total population and stratified by sex and age groups at both spatial scales. In addition, the relative risk (RR) of mortality was estimated to identify vulnerable population groups and regions with a high risk of mortality, using women and the 25–34 age group as reference categories for population-level analysis, and the overall MAVM mortality rate as the reference for municipal-level analysis. Results: Mortality trends showed that circulatory-system diseases (Chapter 9) are emerging as a concerning health issue, with 45 municipalities showing increasing mortality trends, especially among older adults. Respiratory-system diseases (Chapter 10), mental and behavioral disorders (Chapter 5) and nervous-system diseases (Chapter 6) predominantly did not exhibit a consistent general mortality trend. However, upon disaggregating by sex and age groups, specific negative or positive trends emerged at the municipal level for some of these chapters or subgroups. Endocrine, nutritional, and metabolic diseases (Chapter 4) showed a complex pattern, with some age groups presenting increasing mortality trends, and 52 municipalities showing increasing trends overall. The RR showed men and older age groups (≥35 years) exhibiting higher mortality risks. The temporal trend of RR allowed us to identify spatial mortality hotspots mainly in chapters related to circulatory, endocrine, and respiratory diseases, forming four geographical clusters in Mexico City that show persistent high risk of mortality. Conclusions: The spatiotemporal analysis highlights municipalities and vulnerable populations with a consistently elevated mortality risk. These findings emphasize the need for monitoring NCD mortality patterns at both the municipal and metropolitan levels to address disparities and guide the implementation of health policies aimed at reducing mortality risk in vulnerable populations. Full article
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14 pages, 1279 KiB  
Article
Real-World Toxicity and Effectiveness Study of Abemaciclib in Greek Patients with Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: A Multi-Institutional Study
by Elena Fountzilas, Eleni Aravantinou-Fatorou, Katerina Dadouli, Panagiota Economopoulou, Dimitrios Tryfonopoulos, Anastasia Vernadou, Eleftherios Vorrias, Anastasios Vagionas, Adamantia Nikolaidi, Sofia Karageorgopoulou, Anna Koumarianou, Ioannis Boukovinas, Davide Mauri, Stefania Kokkali, Athina Christopoulou, Nikolaos Tsoukalas, Avraam Assi, Nikolaos Spathas, Paris Kosmidis, Angelos Koutras, George Fountzilas and Amanda Psyrriadd Show full author list remove Hide full author list
Cancers 2025, 17(15), 2543; https://doi.org/10.3390/cancers17152543 - 31 Jul 2025
Viewed by 157
Abstract
Background/Objectives: This study aimed to assess real-world toxicity and efficacy data of patients with early and advanced breast cancer (BC) who received treatment with abemaciclib. Methods: This was a prospective/retrospective multi-institutional collection of clinicopathological, toxicity, and outcome data from patients with early or [...] Read more.
Background/Objectives: This study aimed to assess real-world toxicity and efficacy data of patients with early and advanced breast cancer (BC) who received treatment with abemaciclib. Methods: This was a prospective/retrospective multi-institutional collection of clinicopathological, toxicity, and outcome data from patients with early or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative BC who received treatment with abemaciclib in combination with endocrine therapy in departments of oncology in Greece. Treatment combinations of abemaciclib with any endocrine therapy were accepted. The primary end point was toxicity rate in all patients of the study. Results: From June/2021 to May/2024, 245 women received abemaciclib/endocrine combination therapy; the median age was 57 years. Of these, 169 (69%) received abemaciclib as adjuvant therapy for early-stage disease, while 76 (31%) were treated for advanced BC. At the time of the data cutoff, 133 (84.7%) patients remained in the 2-year treatment period. The most common adverse event (AE) was diarrhea (51%), primarily Grade ≤ 2. Dose modifications due to AEs were required in 19.2% of cases, while treatment discontinuation occurred in 5.1%. There was no difference in dose modification/discontinuation rates between older patients (>65 years) and the remaining patients. For early-stage BC patients, the 2-year DFS and OS rates were 90.8% and 100%, respectively. In patients with advanced cancer (70, 30.8%), 1-year PFS and OS rates were 78% and 96.3%, respectively. Conclusions: This study confirms the safety and effectiveness of abemaciclib in alignment with registrational trials offering valuable insights into toxicity management and clinical outcomes in routine practice without identifying new safety concerns. Clinical Trial Registration: ClinicalTrials.gov NCT04985058. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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24 pages, 946 KiB  
Review
Long-Term Adverse Events Following Early Breast Cancer Treatment with a Focus on the BRCA-Mutated Population
by Berta Obispo, Caroline Bailleux, Blanca Cantos, Pilar Zamora, Sachin R. Jhawar, Jajini Varghese, Lucia Cabal-Hierro, Paulo Luz, Luis Berrocal-Almanza and Xiaoqing Xu
Cancers 2025, 17(15), 2506; https://doi.org/10.3390/cancers17152506 - 30 Jul 2025
Viewed by 477
Abstract
Breast cancer (BC) is the most prevalent malignancy in women worldwide. Despite most cases being diagnosed in the early stages, patients typically require a multimodal treatment approach. This typically involves a combination of surgery, radiotherapy, systemic treatments (including chemotherapy or immunotherapy), targeted therapy, [...] Read more.
Breast cancer (BC) is the most prevalent malignancy in women worldwide. Despite most cases being diagnosed in the early stages, patients typically require a multimodal treatment approach. This typically involves a combination of surgery, radiotherapy, systemic treatments (including chemotherapy or immunotherapy), targeted therapy, and endocrine therapy, depending on the disease subtype and the risk of recurrence. Moreover, patients with BC and germline mutations in the breast cancer genes 1 or 2 (BRCA1/BRCA2), (gBRCAm), who are typically young women, often require more aggressive therapeutic interventions. These mutations present unique characteristics that necessitate a distinct treatment approach, potentially influencing the side effect profiles of patients with BC. Regardless of the clear benefit observed with these treatments in terms of reduced recurrence and mortality rates, long-term, treatment-related adverse events occur that negatively affect the health-related quality of life (HRQoL) of BC survivors. Thus, long-term adverse events need to be factored into the treatment decision algorithm of patients with early BC (eBC). Physical, functional, emotional, and psychosocial adverse events can occur and represent a significant concern and a challenge for clinicians, patients, and their families. This review article provides an overview of the various long-term adverse events that patients with eBC may experience, including their associated risk factors, as well as management and prevention strategies. We also explore the evidence of the long-term impact of treatment on the HRQoL of patients with gBRCAm. By providing a comprehensive overview of current evidence and recommendations regarding patients’ HRQoL, we aim to equip clinicians with scientific and clinical knowledge and provide guidance to optimize care and improve long-term outcomes. Full article
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13 pages, 2414 KiB  
Article
In Silico Characterization of Molecular Interactions of Aviation-Derived Pollutants with Human Proteins: Implications for Occupational and Public Health
by Chitra Narayanan and Yevgen Nazarenko
Atmosphere 2025, 16(8), 919; https://doi.org/10.3390/atmos16080919 - 29 Jul 2025
Viewed by 298
Abstract
Combustion of aviation jet fuel emits a complex mixture of pollutants linked to adverse health outcomes among airport personnel and nearby communities. While epidemiological studies showed the detrimental effects of aviation-derived air pollutants on human health, the molecular mechanisms of the interactions of [...] Read more.
Combustion of aviation jet fuel emits a complex mixture of pollutants linked to adverse health outcomes among airport personnel and nearby communities. While epidemiological studies showed the detrimental effects of aviation-derived air pollutants on human health, the molecular mechanisms of the interactions of these pollutants with cellular biomolecules like proteins that drive the adverse health effects remain poorly understood. In this study, we performed molecular docking simulations of 272 pollutant–protein complexes using AutoDock Vina 1.2.7 to characterize the binding strength of the pollutants with the selected proteins. We selected 34 aviation-derived pollutants that constitute three chemical categories of pollutants: volatile organic compounds (VOCs), polyaromatic hydrocarbons (PAHs), and organophosphate esters (OPEs). Each pollutant was docked to eight proteins that play critical roles in endocrine, metabolic, transport, and neurophysiological functions, where functional disruption is implicated in disease. The effect of binding of multiple pollutants was analyzed. Our results indicate that aliphatic and monoaromatic VOCs display low (<6 kcal/mol) binding affinities while PAHs and organophosphate esters exhibit strong (>7 kcal/mol) binding affinities. Furthermore, the binding strength of PAHs exhibits a positive correlation with the increasing number of aromatic rings in the pollutants, ranging from nearly 7 kcal/mol for two aromatic rings to more than 15 kcal/mol for five aromatic rings. Analysis of intermolecular interactions showed that these interactions are predominantly stabilized by hydrophobic, pi-stacking, and hydrogen bonding interactions. Simultaneous docking of multiple pollutants revealed the increased binding strength of the resulting complexes, highlighting the detrimental effect of exposure to pollutant mixtures found in ambient air near airports. We provide a priority list of pollutants that regulatory authorities can use to further develop targeted mitigation strategies to protect the vulnerable personnel and communities near airports. Full article
(This article belongs to the Section Air Quality and Health)
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22 pages, 6395 KiB  
Article
Investigation of Novel Therapeutic Targets for Rheumatoid Arthritis Through Human Plasma Proteome
by Hong Wang, Chengyi Huang, Kangkang Huang, Tingkui Wu and Hao Liu
Biomedicines 2025, 13(8), 1841; https://doi.org/10.3390/biomedicines13081841 - 29 Jul 2025
Viewed by 364
Abstract
Background: Rheumatoid arthritis (RA) is an autoimmune disease that remains incurable. An increasing number of proteomic genome-wide association studies (GWASs) are emerging, offering immense potential for identifying novel therapeutic targets for diseases. This study aims to identify potential therapeutic targets for RA [...] Read more.
Background: Rheumatoid arthritis (RA) is an autoimmune disease that remains incurable. An increasing number of proteomic genome-wide association studies (GWASs) are emerging, offering immense potential for identifying novel therapeutic targets for diseases. This study aims to identify potential therapeutic targets for RA based on human plasma proteome. Methods: Protein quantitative trait loci were extracted and integrated from eight large-scale proteomic GWASs. Proteome-wide Mendelian randomization (Pro-MR) was performed to prioritize proteins causally associated with RA. Further validation of the reliability and stratification of prioritized proteins was performed using MR meta-analysis, colocalization, and transcriptome-wide summary-data-based MR. Subsequently, prioritized proteins were characterized through protein–protein interaction and enrichment analyses, pleiotropy assessment, genetically engineered mouse models, cell-type-specific expression analysis, and druggability evaluation. Phenotypic expansion analyses were also conducted to explore the effects of the prioritized proteins on phenotypes such as endocrine disorders, cardiovascular diseases, and other immune-related diseases. Results: Pro-MR prioritized 32 unique proteins associated with RA risk. After validation, prioritized proteins were stratified into four reliability tiers. Prioritized proteins showed interactions with established RA drug targets and were enriched in an immune-related functional profile. Four trans-associated proteins exhibited vertical or horizontal pleiotropy with specific genes or proteins. Genetically engineered mouse models for 18 prioritized protein-coding genes displayed abnormal immune phenotypes. Single-cell RNA sequencing data were used to validate the enriched expression of several prioritized proteins in specific synovial cell types. Nine prioritized proteins were identified as targets of existing drugs in clinical trials or were already approved. Further phenome-wide MR and mediation analyses revealed the effects and potential mediating roles of some prioritized proteins on other phenotypes. Conclusions: This study identified 32 plasma proteins as potential therapeutic targets for RA, expanding the prospects for drug discovery and deepening insights into RA pathogenesis. Full article
(This article belongs to the Section Gene and Cell Therapy)
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22 pages, 1241 KiB  
Systematic Review
Safety and Efficacy of Immune Checkpoint Inhibitors in Human Immunodeficiency Virus-Associated Cancer: A Systematic Scoping Review
by Ahmed D. Alatawi, Amirah B. Alaqyl, Reema J. Alalawi, Rahaf S. Alqarni, Razan A. Sufyani, Ghadi S. Alqarni, Raghad S. Alqarni, Jumana H. Albalawi, Raghad A. Alsharif, Ghada I. Alatawi, Elaf N. Albalawi, Danah A. Alanazi, Sultanah A. Naitah, Reem Sayad and Helal F. Hetta
Diseases 2025, 13(8), 230; https://doi.org/10.3390/diseases13080230 - 22 Jul 2025
Viewed by 377
Abstract
Background/Objective: People living with human immunodeficiency virus (PHIV) are at increased risk for malignancies, yet their access to immunotherapy remains limited due to concerns about safety and efficacy. This systematic scoping review evaluates the use of immune checkpoint inhibitors (ICIs) in HIV-associated cancers, [...] Read more.
Background/Objective: People living with human immunodeficiency virus (PHIV) are at increased risk for malignancies, yet their access to immunotherapy remains limited due to concerns about safety and efficacy. This systematic scoping review evaluates the use of immune checkpoint inhibitors (ICIs) in HIV-associated cancers, analyzing patient outcomes, safety profiles, and the impact on HIV status. Methods: A comprehensive literature search was conducted in databases including PubMed, Scopus, Web of Science (WoS), and Medline, up to January 2025. Studies included assessing the efficacy of ICIs in cancer patients with HIV. The primary outcomes were (a) the efficacy of immune ICIs on prognosis, progression-free survival (PFS), and overall survival (OS). Secondary outcomes were the immune-related adverse events (irAEs) and the survival rate of cancer patients receiving ICIs. Results: A total of 107 cases from 19 studies published between 2011 and 2024 were reviewed. Responses to programmed death 1 (PD-1) inhibitors varied, with 27.1% achieving partial response, 23.36% experiencing stable disease, and 6.54% achieving complete response, while 34.57% had disease progression. Adverse events, including hematologic and endocrine toxicities, were common but mostly manageable. HIV viral loads remained stable in most cases. Conclusions: PD-1 inhibitors demonstrated potential efficacy in HIV-associated malignancies with a safety profile comparable to the general population. However, disease progression remained a concern, highlighting the need for optimized patient selection. Further well-controlled trials are essential to establish treatment guidelines and ensure equitable access to immunotherapy for PHIV. Full article
(This article belongs to the Special Issue Cancer Inhibitory Receptors and Related Cancer Immunotherapy)
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29 pages, 1989 KiB  
Review
Dietary Flavonoids Vitexin and Isovitexin: New Insights into Their Functional Roles in Human Health and Disease Prevention
by Weiqi Yan, Junying Cheng and Baojun Xu
Int. J. Mol. Sci. 2025, 26(14), 6997; https://doi.org/10.3390/ijms26146997 - 21 Jul 2025
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Abstract
Vitexin and isovitexin are dietary flavonoids widely distributed in food and medicinal plants. They have attracted increasing attention owing to their diverse pharmacological activities and favorable safety profiles. These compounds exhibit therapeutic potential across multiple biological systems, including the immune, nervous, respiratory, cardiovascular, [...] Read more.
Vitexin and isovitexin are dietary flavonoids widely distributed in food and medicinal plants. They have attracted increasing attention owing to their diverse pharmacological activities and favorable safety profiles. These compounds exhibit therapeutic potential across multiple biological systems, including the immune, nervous, respiratory, cardiovascular, and endocrine systems, through antioxidant, anti-inflammatory, anticancer, antibacterial, and neuroprotective mechanisms. Although previous reviews have addressed the pharmacological effects of vitexin and isovitexin, most are limited in scope—either focusing solely on vitexin or restricted to specific disease models such as cancer or diabetes. Moreover, some studies are outdated and do not reflect the recent advances in synthetic modification, green extraction technologies, and systems pharmacology. This review aims to provide a comprehensive evaluation of the pharmacological properties, pharmacokinetics, and clinical relevance of vitexin and isovitexin, highlighting their potential in disease prevention and treatment. A literature search was conducted using Web of Science, PubMed, and Google Scholar, with keywords including “vitexin”, “isovitexin”, “disease”, and “mechanism”. Here, we summarize the current research on the pharmacological effects of vitexin and isovitexin in metabolic disorders, inflammatory diseases, cancer, and neurodegenerative conditions, focusing on their molecular mechanisms and therapeutic targets. Furthermore, we discussed their toxicity, bioavailability, pharmacokinetics, and clinical research findings. Vitexin and isovitexin hold promise as therapeutic agents or adjuncts for multiple diseases with potential applications in modern medicine and healthcare. However, their pharmacological mechanisms, clinical efficacy, and potential synergistic effects with other therapeutic agents remain unclear. Further systematic research is needed to clarify molecular targets and optimize their therapeutic applications. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Bioactive Nutrients Promoting Human Health)
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13 pages, 388 KiB  
Article
Benchmarking ChatGPT-3.5 and OpenAI o3 Against Clinical Pharmacists: Preliminary Insights into Clinical Accuracy, Sensitivity, and Specificity in Pharmacy MCQs
by Esraa M. Alsaudi, Sireen A. Shilbayeh and Rana K Abu-Farha
Healthcare 2025, 13(14), 1751; https://doi.org/10.3390/healthcare13141751 - 19 Jul 2025
Viewed by 506
Abstract
Objective: This proof-of-concept study aimed to evaluate and compare the clinical performance of two AI language models (ChatGPT-3.5 and OpenAI o3) in answering clinical pharmacy multiple-choice questions (MCQs), benchmarked against responses from specialist clinical pharmacists in Jordan, including academic preceptors and hospital-based clinicians. [...] Read more.
Objective: This proof-of-concept study aimed to evaluate and compare the clinical performance of two AI language models (ChatGPT-3.5 and OpenAI o3) in answering clinical pharmacy multiple-choice questions (MCQs), benchmarked against responses from specialist clinical pharmacists in Jordan, including academic preceptors and hospital-based clinicians. Methods: A total of 60 clinical pharmacy MCQs were developed based on current guidelines across four therapeutic areas: cardiovascular, endocrine, infectious, and respiratory diseases. Each item was reviewed by academic and clinical experts and then pilot-tested with five pharmacists to determine clarity and difficulty. Two ChatGPT models—GPT-3.5 and OpenAI o3—were tested using a standardized prompt for each MCQ, entered in separate sessions to avoid memory retention. Their answers were classified as true/false positives or negatives and retested after two weeks to assess reproducibility. Simultaneously, 25 licensed pharmacists (primarily from one academic institution and several hospitals in Amman) completed the same MCQs using validated references (excluding AI tools). Accuracy, sensitivity, specificity, and Cohen’s Kappa were used to compare AI and human performance, with statistical analysis conducted using appropriate tests at a significance level of p ≤ 0.05. Results: OpenAI o3 achieved the highest accuracy (83.3%), sensitivity (90.0%), and specificity (70.0%), outperforming GPT-3.5 (70.0%, 77.5%, 55.0%) and pharmacists (69.7%, 77.0%, 55.0%). AI performance declined significantly with increasing question difficulty. OpenAI o3 showed the highest accuracy in the cardiovascular domain (93.3%), while GPT-3.5 performed best in infectious diseases (80.0%). Reproducibility was higher for GPT-3.5 (81.6%, κ = 0.556) than OpenAI o3 (76.7%, κ = 0.364). Over two test rounds, GPT-3.5’s accuracy remained stable, whereas OpenAI o3’s accuracy decreased from 83.3% to 70.0%, indicating some variability. Conclusions: OpenAI o3 shows strong promise as a clinical decision-support tool in pharmacy, especially for low- to moderate-difficulty questions. However, inconsistencies in reproducibility and limitations in complex cases highlight the importance of cautious, supervised integration alongside human expertise. Full article
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