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Search Results (3,786)

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Keywords = receptor for AGEs

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20 pages, 3602 KB  
Article
Kaempferol Regulates Lipid Homeostasis, Endocannabinoid System, and PPARα in Rat Cerebral Cortex Following BCCAO/R
by Gianfranca Carta, Maria Pina Serra, Elisabetta Murru, Marianna Boi, Claudia Manca, Ylenia Lai, Monica Cabboi, Antonella Carta, Sebastiano Banni and Marina Quartu
Biomolecules 2025, 15(10), 1440; https://doi.org/10.3390/biom15101440 (registering DOI) - 11 Oct 2025
Abstract
Previous research has demonstrated that the transient bilateral common carotid artery occlusion and reperfusion (BCCAO/R) effectively models early brain inflammation resulting from sudden hypoperfusion and subsequent reperfusion. According to studies showing that diet and nutrition strongly influence brain neuroplasticity, in this study we [...] Read more.
Previous research has demonstrated that the transient bilateral common carotid artery occlusion and reperfusion (BCCAO/R) effectively models early brain inflammation resulting from sudden hypoperfusion and subsequent reperfusion. According to studies showing that diet and nutrition strongly influence brain neuroplasticity, in this study we evaluated whether kaempferol (KAM), a dietary flavonoid, offers neuroprotection in a rat BCCAO/R model. Adult Wistar rats were gavage fed a single dose of KAM (40 mg) six hours before surgery. Comprehensive lipidomic and molecular analyses were conducted on samples from the frontal and temporal-occipital cortices, as well as the plasma. In the frontal cortex, KAM elevated anti-inflammatory N-acylethanolamines palmitoylethanolamide (PEA), oleoylethanolamide (OEA), and docosahexaenoylethanolamide (DHAEA) and reduced oxidized arachidonic acid metabolites. KAM also downregulated cyclooxygenase- 2 (COX-2) protein and selectively decreased the endocannabinoid 2-arachidonoylglycerol (2-AG), showing a shift in AA metabolism. These molecular changes correlated with increased levels of peroxisome proliferator-activated receptor alpha (PPARα) and cannabinoid receptors CB1R and CB2R, supporting activation of both nuclear and membrane-bound anti-inflammatory pathways. No significant changes were observed in the temporal-occipital cortex. In plasma, DHAEA levels increased similarly to those in the cortex. However, rises in PEA and OEA were detected only in sham-operated KAM-treated animals, suggesting possible central redistribution under hypoperfusion/reperfusion stress. In summary, these findings demonstrate that KAM exerts dual anti-inflammatory effects by inhibiting COX-2-mediated prostanoid synthesis and promoting PPARα-driven lipid signaling. This dual mechanism highlights the potential of KAM as a dietary intervention to reduce neuroinflammation associated with hypoperfusion–reperfusion challenges. Full article
(This article belongs to the Special Issue Lipid Signaling in Neuroinflammation and Neurodegeneration)
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21 pages, 1070 KB  
Article
Genetic Variations in Bitter Taste Receptors and COVID-19 in the Canadian Longitudinal Study on Aging
by Marziyeh Shafizadeh, Mohd Wasif Khan, Britt Drögemöller, Chrysi Stavropoulou, Philip St. John, Rajinder P. Bhullar, Prashen Chelikani and Carol A. Hitchon
Biomedicines 2025, 13(10), 2473; https://doi.org/10.3390/biomedicines13102473 (registering DOI) - 11 Oct 2025
Abstract
Background/Objectives: Bitter Taste Receptors (encoded by TAS2R genes) are expressed in mucosal and bronchial epithelia, as well as in immune cells, contributing to defense against airborne pathogens such as SARS-CoV-2. Data on single-nucleotide polymorphisms (SNPs) in TAS2R genes or pseudogenes in COVID-19 are [...] Read more.
Background/Objectives: Bitter Taste Receptors (encoded by TAS2R genes) are expressed in mucosal and bronchial epithelia, as well as in immune cells, contributing to defense against airborne pathogens such as SARS-CoV-2. Data on single-nucleotide polymorphisms (SNPs) in TAS2R genes or pseudogenes in COVID-19 are limited. This study examined the association between TAS2R SNPs and COVID-19 infection and seroconversion in European individuals participating in the Canadian Longitudinal Study on Aging. Methods: Data from the Genome-wide Genetic Data, Comprehensive Baseline (version 7.0), Follow-up 2 (version 1.1), COVID-19 Questionnaire Study (4-2020 to 12-2020), and COVID-19 Seroprevalence (Antibody) Study (11-2020 to 7-2021) datasets were accessed. Associations of TAS2R SNPS with COVID-19 infection or seroconversion were determined using logistic regression adjusted for sociodemographics, genetic principal components, smoking, vaccine doses, and chronic medical conditions (diabetes, immune-mediated inflammatory diseases (IMIDs), respiratory disease, and cardiovascular disease). Results: In the COVID-19 Questionnaire Study (N = 14,073), the rs117458236 (C) variant in TAS2R20 showed a trend toward an association with COVID-19 infection (OR = 1.95; 95% Confidence Interval (CI): 0.98, 3.51). In the COVID-19 Antibody Study (N = 8313), the rs2234235(G) variant in TAS2R1 was associated with anti-nucleocapsid (OR = 1.55; CI: 1.06, 2.20) and anti-spike response (OR = 0.74; CI: 0.57, 0.98); the rs2234010(A) variant in TAS2R5 was associated with anti-nucleocapsid (OR = 1.56; CI: 1.08, 2.19); and the rs34039200(A) variant in TAS2R62P was associated with anti-spike (OR = 0.86; CI: 0.77, 0.97). In a subgroup analysis, the rs2234235(G) variant in TAS2R1 was associated with a decreased anti-spike response to infection or vaccination in individuals with IMIDs or respiratory disease and an increased risk of SARS-CoV-2 infection. Conclusions: TAS2R variants are associated with COVID-19 infection and vaccine response. These data may inform personalized management and vaccination strategies. Full article
(This article belongs to the Section Molecular Genetics and Genetic Diseases)
17 pages, 883 KB  
Article
Trends in Conventional Heart Failure Therapy in a Real-World Multinational ATTR-CA Cohort
by Eva H. van der Geest, Nina Ajmone Marsan, Dorien Laenens, Philippe J. M. R. Debonnaire, Mathias Claeys, Fauto Pinto, Dulce Brito, Erwan Donal, Steven Droogmans, Nico Van de Veire, Philippe Bertrand, Takeru Nabeta, Francesca Graziani and Madelien V. Regeer
J. Cardiovasc. Dev. Dis. 2025, 12(10), 403; https://doi.org/10.3390/jcdd12100403 (registering DOI) - 11 Oct 2025
Abstract
Background: Conventional HF treatment in transthyretin cardiac amyloidosis (ATTR-CA) resulting in restrictive cardiomyopathy is debated due to absent trial evidence in this specific sub-population of heart failure (HF) patients. Current European Society of Cardiology guidelines recommend the use of diuretics and mineralocorticoid receptor [...] Read more.
Background: Conventional HF treatment in transthyretin cardiac amyloidosis (ATTR-CA) resulting in restrictive cardiomyopathy is debated due to absent trial evidence in this specific sub-population of heart failure (HF) patients. Current European Society of Cardiology guidelines recommend the use of diuretics and mineralocorticoid receptor antagonists (MRAs). However, beta-blockers (BBs) and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs) are often discontinued due to hypotension or bradycardia. This study assesses real-world HF treatment patterns and their impact on survival in a multinational ATTR-CA cohort. Methods: A retrospective analysis of 794 ATTR-CA patients examined baseline BB, ACEi/ARB, and MRA prescriptions. The cohort was divided based on guideline publication dates. Results: Patients were predominantly male (73.2%) with a median age of 78 years. Prescription of diuretics (52.8%) and disease-modifying therapy (44.9%), mostly tafamidis, was common. BBs (43.7%) and ACEi/ARBs (41.2%) were prescribed more often in patients with higher NYHA class, elevated NT-proBNP, and more comorbidities. Blood pressure and heart rate were similar regardless of BB or ACEi/ARB use. BB prescription and combination therapy with BB and ACEi/ARB increased over time. Neither BB nor ACEi/ARB use significantly impacted mortality when analyzed in a multivariate Cox proportional hazard regression. Conclusions: Use of BBs and ACEi/ARBs has increased over time, particularly in advanced-stage ATTR-CA patients, and although these therapies appear to be reasonably tolerated, survival was not significantly altered. Full article
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13 pages, 1781 KB  
Perspective
A Neural-Glial Model of the ApoE-SORT1-FABP7 Axis Tied to Sleep Disruption and Alzheimer’s Disease Pathophysiology
by Carlos C. Flores, Yool Lee, Christopher J. Davis, Patrick Solverson and Jason R. Gerstner
Biomolecules 2025, 15(10), 1432; https://doi.org/10.3390/biom15101432 - 10 Oct 2025
Viewed by 42
Abstract
Alzheimer’s disease (AD) is a complex neurodegenerative disorder where age, genetic factors and sleep disturbance significantly influence disease risk. Recent genome-wide association studies identified a C/T missense variant (rs141749679) in the sortilin (SORT1) gene linked to heightened AD risk, revealing SORT1’s [...] Read more.
Alzheimer’s disease (AD) is a complex neurodegenerative disorder where age, genetic factors and sleep disturbance significantly influence disease risk. Recent genome-wide association studies identified a C/T missense variant (rs141749679) in the sortilin (SORT1) gene linked to heightened AD risk, revealing SORT1’s role as a key player in the disease’s pathophysiology. This type I membrane glycoprotein is implicated in amyloid β (Aβ) accumulation and associated lipid dysregulation, particularly through its interaction with apolipoprotein E (ApoE). SORT1 facilitates the uptake of ApoE-bound polyunsaturated fatty acids (PUFAs), conversion to endocannabinoids (eCBs), and the regulation of anti-inflammatory pathways via peroxisome proliferator-activated receptors (PPARs). Notably, this neuroprotective signaling is contingent on the APOE allele, exhibiting functionality in presence of ApoE3 but disrupted with ApoE4. Additionally, the brain-type fatty acid binding protein, FABP7, mediates this signaling cascade, emphasizing its role in neuron-glia communication. FABP7 is known to regulate sleep across species and binds PUFAs and eCBs. Therefore, dysfunction of the ApoE-SORT1-FABP7 axis may underlie the neuroprotective loss observed in AD, linking sleep disruption and lipid homeostasis to disease progression. This perspective aims to elucidate the intricate neural-glial mechanisms governing the ApoE-SORT1-FABP7 interaction and their implications for targeting therapeutic interventions in Alzheimer’s disease. Full article
(This article belongs to the Special Issue Lipid Signaling in Neuroinflammation and Neurodegeneration)
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12 pages, 351 KB  
Review
Ocular Effects of GLP-1 Receptor Agonists: A Review of Current Evidence and Safety Concerns
by Giuseppe Maria Albanese, Giacomo Visioli, Ludovico Alisi, Francesca Giovannetti, Luca Lucchino, Marta Armentano, Fiammetta Catania, Marco Marenco and Magda Gharbiya
Diabetology 2025, 6(10), 117; https://doi.org/10.3390/diabetology6100117 - 10 Oct 2025
Viewed by 79
Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as cornerstone therapies for type 2 diabetes mellitus and obesity, offering significant cardiovascular and renal protection. However, recent evidence has sparked interest and concern regarding their potential ocular effects. This review critically synthesizes current data on [...] Read more.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as cornerstone therapies for type 2 diabetes mellitus and obesity, offering significant cardiovascular and renal protection. However, recent evidence has sparked interest and concern regarding their potential ocular effects. This review critically synthesizes current data on the impact of GLP-1RAs on diabetic retinopathy (DR), nonarteritic anterior ischemic optic neuropathy (NAION), age-related macular degeneration (AMD), and glaucoma or ocular hypertension. While preclinical studies suggest GLP-1RAs exert anti-inflammatory and neuroprotective effects in retinal tissues, clinical data remain mixed. Several large observational studies suggest a protective role against DR and glaucoma, while others raise safety concerns, particularly regarding semaglutide and NAION. Evidence on AMD is conflicting, with signals of both benefit and risk. We also discuss plausible pathophysiological mechanisms and the relevance of metabolic modulation on retinal perfusion. Overall, while GLP-1RAs hold promise for ocular protection in some contexts, vigilance is warranted, especially in patients with pre-existing eye disease. Further ophthalmology-focused prospective trials are essential to clarify long-term safety and guide clinical decision making. Full article
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19 pages, 1175 KB  
Article
The Effect of the Clinical-Pathological CPS+EG Staging System on Survival Outcomes in Patients with HER2-Positive Breast Cancer Receiving Neoadjuvant Treatment: A Retrospective Study
by Seval Orman, Miray Aydoğan, Oğuzcan Kınıkoğlu, Sedat Yıldırım, Nisanur Sarıyar Busery, Hacer Şahika Yıldız, Ezgi Türkoğlu, Tuğba Kaya, Deniz Işık, Seval Ay Ersoy, Hatice Odabaş and Nedim Turan
Medicina 2025, 61(10), 1813; https://doi.org/10.3390/medicina61101813 - 9 Oct 2025
Viewed by 201
Abstract
Background and Objectives: To evaluate the prognostic value of the Clinical–Pathologic Stage–Estrogen receptor status and Grade (CPS+EG) staging system, which combines clinical staging, pathological staging, oestrogen receptor (ER) status, and tumour grade in predicting survival outcomes in patients with human epidermal growth [...] Read more.
Background and Objectives: To evaluate the prognostic value of the Clinical–Pathologic Stage–Estrogen receptor status and Grade (CPS+EG) staging system, which combines clinical staging, pathological staging, oestrogen receptor (ER) status, and tumour grade in predicting survival outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant therapy (NACT). Materials and Methods: A retrospective review was performed on 245 female breast cancer patients who received anti-HER2 therapy alongside NACT at the Medical Oncology Department of Kartal Dr Lütfi Kırdar City Hospital, University of Health Sciences, from April 2012 to June 2024. The CPS+EG score was calculated using the MD Anderson Cancer Centre neoadjuvant treatment response calculator. Patients were categorised into two groups based on their CPS+EG score < 3 and ≥3. The primary outcomes assessed were disease-free survival (DFS) and overall survival (OS). Kaplan–Meier and log-rank tests were utilised for time-to-event analysis; Cox regression was used for multivariate analysis. A significance level of ≤0.05 was considered. Results: The median age of the patient cohort was 51 years (range: 27–82 years). Among these patients, 183 (74.6%) had a CPS+EG score less than 3, while 62 (25.3%) exhibited a score of 3 or higher. The median follow-up duration was 37.6 months. The pathological complete response (pCR) rate across the entire cohort was 51.8%. Specifically, the pCR rate was 56.3% in the group with CPS+EG scores below 3, and 38.7% in those with scores of 3 or higher (p = 0.017). Patients with CPS+EG scores less than 3 demonstrated superior overall survival (OS), which reached statistical significance in univariate analysis. Multivariate analysis identified the CPS+EG score as an independent prognostic factor for both overall survival and disease-free survival (DFS), with hazard ratios of 0.048 (95% CI: 0.004–0.577, p = 0.017) and 0.35 (95% CI: 0.14–0.86, p = 0.023), respectively. Conclusions: The CPS+EG score is an independent and practical prognostic marker, particularly for overall survival, in patients with HER2-positive breast cancer who have received neoadjuvant therapy. Patients with a CPS+EG score < 3 have higher pCR rates and survival rates. When used in conjunction with pCR, it can improve risk categorisation and contribute to the individualisation of adjuvant strategies in the post-neoadjuvant period. Due to its ease of calculation and lack of additional costs, this score can be instrumental in clinical practice for identifying high-risk patients. Our findings support the integration of the CPS+EG score into routine clinical decision-making processes, although prospective validation studies are necessary. Full article
(This article belongs to the Special Issue New Developments in Diagnosis and Management of Breast Cancer)
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38 pages, 8212 KB  
Article
Immunoinformatic Prediction of HIV-1 Glycoprotein gp120 and Nef Epitopes Conjugated to HBsAg-Binding Protein (SBP) to Induce the Humoral and Cellular Immune Response
by Arslan Habib, Xinyi Xu, Jun Xie and Naishuo Zhu
Int. J. Mol. Sci. 2025, 26(19), 9828; https://doi.org/10.3390/ijms26199828 - 9 Oct 2025
Viewed by 200
Abstract
Acquired Immunodeficiency Syndrome (AIDS) is caused by Human Immunodeficiency Virus (HIV), and continues to be responsible for a substantial number of deaths worldwide each year. Development of a robust and efficient HIV-1 vaccine remains a critical priority. Structural analysis of viral proteins provides [...] Read more.
Acquired Immunodeficiency Syndrome (AIDS) is caused by Human Immunodeficiency Virus (HIV), and continues to be responsible for a substantial number of deaths worldwide each year. Development of a robust and efficient HIV-1 vaccine remains a critical priority. Structural analysis of viral proteins provides a foundational approach to designing peptide-based immunogenic vaccines. In the current experiment, we used computational prediction approaches alongside molecular docking and molecular dynamics (MD) simulations to identify potential epitopes within gp120 and Nef proteins. The selected co-epitopes were fused with the HBsAg-binding protein (SBP), a 344-amino acid protein previously identified in our laboratory through screening of a human liver cDNA expression library against HBsAg, to facilitate efficient delivery to and uptake by dendritic cells (DCs), thereby enhancing antigen (Ag) presentation. Flexible linkers are used to connect B cells, Helper T Lymphocytes (HTLs), and Cytotoxic T Lymphocytes (CTLs) in a sequential manner. The assembled vaccine construct comprises 757 amino acids, corresponding to a recombinant protein of 83.64 kDa molecular weight. Structural analysis through docking studies, MD simulations, and 3D structure validation revealed that the designed protein exhibits high structural stability and potential for interaction with Toll-like receptors (TLRs). These findings support the vaccine’s ability to enhance cellular and humoral feedback, including the stimulation of T and B cells and induction of antibody (Ab) production. The results underscore the promise of this in silico designed co-epitope vaccine as a viable candidate for HIV-1 prevention and suggest that such constructs may serve as effective immunogens in future HIV-1 vaccine strategies. Full article
(This article belongs to the Section Molecular Informatics)
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16 pages, 4419 KB  
Article
PUM1 in Breast Cancer: Tumor Expression and Prognostic and Predictive Significance
by Abrar I. Aljohani
Medicina 2025, 61(10), 1810; https://doi.org/10.3390/medicina61101810 - 9 Oct 2025
Viewed by 197
Abstract
Background and Objectives: Breast cancer (BC) is a complex disease requiring a comprehensive treatment approach due to its diverse characteristics. Critical molecular determinants of BC have been identified using advanced genomic, transcriptomic, and proteomic approaches. Assessing the biomarkers associated with the onset [...] Read more.
Background and Objectives: Breast cancer (BC) is a complex disease requiring a comprehensive treatment approach due to its diverse characteristics. Critical molecular determinants of BC have been identified using advanced genomic, transcriptomic, and proteomic approaches. Assessing the biomarkers associated with the onset of early-stage BC may help identify the risk of metastasis and inform treatment decisions. A previous bioinformatic analysis using two large BC cohorts identified pumilio RNA binding family member 1 (PUM1) as a key gene in invasive BC. However, no study has yet examined the prognostic and predictive value of PUM1 in invasive BC and its correlation with aggressive tumor behavior. This study aimed to fill this need. Materials and Methods: Correlations between PUM1 expression and patients’ clinicopathological characteristics and outcomes were explored in publicly available BC transcriptomic data acquired using DNA microarrays (n = 10,872) and RNA sequencing (n = 4421) using BC Gene-Expression Miner v5.0. PUM1 expression in samples from 100 patients with invasive BC at King Abdul Aziz Specialist Hospital, Saudi Arabia, was assessed immunohistochemically. Correlations between PUM1 expression and patients’ clinicopathological characteristics (e.g., age, tumor grade, tumor size, and outcome) were assessed. The online platform ROC Plotter was also used to investigate the predictive significance of PUM1. Results: High PUM1 gene and protein expression correlated positively with aggressive features of BC, including high histological grade, high Ki-67 expression, negative hormone receptors, and the triple-negative BC molecular subtype. High PUM1 expression correlated with poor outcomes, and high PUM1 expression was associated with a lower pathological complete response to anti-endocrine treatment but a high response to chemotherapy. Conclusions: These results indicate that PUM1 may serve as a potential prognostic and predictive biomarker in patients with invasive BC. PUM1 may serve as a therapeutic target in BC cases with unfavorable prognoses. However, further validation in larger, multi-center cohorts and further functional assessment are required to deepen our understanding of PUM1’s role in BC. Full article
(This article belongs to the Section Oncology)
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14 pages, 841 KB  
Review
Cosmetic Considerations of Semaglutide
by Alaina Baggett, Carissa Saadi, Robert Saadi and Vijay Patel
Cosmetics 2025, 12(5), 221; https://doi.org/10.3390/cosmetics12050221 - 9 Oct 2025
Viewed by 246
Abstract
Semaglutide-induced facial changes, or “Ozempic face” popularized by media, have gained increasing recognition since the widespread and growing use of Ozempic (semaglutide) for weight loss. It refers to facial volume depletion and soft tissue laxity following rapid weight loss associated with this medication. [...] Read more.
Semaglutide-induced facial changes, or “Ozempic face” popularized by media, have gained increasing recognition since the widespread and growing use of Ozempic (semaglutide) for weight loss. It refers to facial volume depletion and soft tissue laxity following rapid weight loss associated with this medication. Semaglutide use can also cause gastrointestinal side effects, volume loss, and decrease skin quality not only in the face but globally. As the use of Ozempic becomes increasingly popular, more patients are presenting to cosmetic clinics for these undesirable esthetic changes. While cosmetic changes following rapid weight loss is not new, such as those following bariatric interventions, the accessibility and ease of GLP-1, Glucose-like protein-1, makes this a growing concern among the community. It is important for clinicians to recognize these potential effects, counsel patients appropriately, and give options for treatment. This emerging esthetic concern highlights the need for further investigation into underlying causes, risk factors, and potential interventions. Full article
(This article belongs to the Special Issue Feature Papers in Cosmetics in 2025)
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29 pages, 2125 KB  
Review
Hungry Bone Syndrome After Parathyroidectomy for Secondary Hyperparathyroidism: Pathogenesis and Contemporary Clinical Considerations
by Adina Coman, Cristi Tarta, Marco Marian, Daian Ionel Popa, Sorin Olariu, Mihai Rosu, Diana Utu, Florina Buleu, Anca-Monica Macovei-Oprescu, Dorin Novacescu, Flavia Zara and Marius Murariu
J. Clin. Med. 2025, 14(19), 7104; https://doi.org/10.3390/jcm14197104 - 9 Oct 2025
Viewed by 240
Abstract
Secondary hyperparathyroidism (SHPT) in chronic kidney disease often necessitates parathyroidectomy (PTX), but this definitive treatment can precipitate hungry bone syndrome (HBS)—a profound, prolonged hypocalcemia caused by the rapid skeletal uptake of minerals after surgery. HBS results from the abrupt cessation of parathyroid hormone [...] Read more.
Secondary hyperparathyroidism (SHPT) in chronic kidney disease often necessitates parathyroidectomy (PTX), but this definitive treatment can precipitate hungry bone syndrome (HBS)—a profound, prolonged hypocalcemia caused by the rapid skeletal uptake of minerals after surgery. HBS results from the abrupt cessation of parathyroid hormone (PTH)-driven bone resorption while bone formation continues, leading to intensive mineral deposition (mainly calcium) into chronically demineralized bone. Clinically, HBS ranges from asymptomatic biochemical disturbances to life-threatening hypocalcemia with tetany, seizures, and/or cardiac arrhythmias. This illustrative review synthesizes current knowledge of HBS pathogenesis and management in the context of SHPT. We detail how the high-turnover bone remodeling state of SHPT (osteitis fibrosa cystica) creates an expansive unmineralized osteoid pool that avidly mineralizes post-PTX. We also explore molecular mechanisms (e.g., RANKL/OPG dysregulation, Wnt/β-catenin activation, osteocyte-driven signals, and calcium-sensing receptor effects) that underpin this process. Key preoperative risk factors for HBS include very elevated PTH and alkaline phosphatase levels, large skeletal calcium deficits, younger patient age, and total PTX. We outline the typical postoperative course of HBS, phased from immediate acute hypocalcemia to a nadir and gradual recovery. Prevention and management strategies are emphasized, centered on vigilant monitoring and aggressive calcium and calcitriol supplementation, with preoperative optimization (e.g., vitamin D loading, calcimimetics) to mitigate severity. By enhancing risk stratification and perioperative care, clinicians can improve outcomes and safely navigate patients through this challenging complication of endocrine surgery. Full article
(This article belongs to the Special Issue Endocrine Surgery: Current Developments and Trends)
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13 pages, 2998 KB  
Article
TMPRSS2 Expression in Lung Tissue of Prostatic Adenocarcinoma Patients: Androgen Deprivation Therapy and Relevance to SARS-CoV-2 Infection
by Marcela Riveros Angel, David Loeffler, Ahmad Charifa, Ryan B. Sinit, Taylor Amery, Beyza Cengiz, Tomasz M. Beer and George V. Thomas
Curr. Issues Mol. Biol. 2025, 47(10), 823; https://doi.org/10.3390/cimb47100823 - 8 Oct 2025
Viewed by 148
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry is facilitated by transmembrane protease serine 2 (TMPRSS2), which is regulated by the androgen receptor (AR). Androgen deprivation therapy (ADT), widely used in prostate cancer treatment, may potentially modulate TMPRSS2 expression, affecting SARS-CoV-2 infection [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry is facilitated by transmembrane protease serine 2 (TMPRSS2), which is regulated by the androgen receptor (AR). Androgen deprivation therapy (ADT), widely used in prostate cancer treatment, may potentially modulate TMPRSS2 expression, affecting SARS-CoV-2 infection susceptibility and severity. We evaluated the impact of ADT on pulmonary TMPRSS2 expression in prostate cancer patients and analyzed differences in expression patterns associated with specific ADT regimens. We examined TMPRSS2 immunohistochemical expression in lung tissue from 20 consecutive autopsy cases of men with prostate cancer (6 receiving ADT at time of death), compared with non-ADT prostate cancer patients and age-matched women controls. Histoscores were calculated by assessing the percentage and intensity of pneumocyte TMPRSS2 expression. Prostate cancer patients receiving ADT showed significantly reduced pulmonary TMPRSS2 expression compared to non-ADT patients (mean histoscores: 152.7 vs. 225.0, p = 0.037) and age-matched women controls (mean histoscores: 152.7 vs. 238.0, p = 0.024). Direct AR antagonists (apalutamide, bicalutamide) produced greater TMPRSS2 suppression than Gonadotropin-Releasing Hormone modulators or androgen biosynthesis inhibitors. No significant correlation was observed between the TMPRSS2 expression and Gleason score, PSA levels, or underlying lung pathology. Our findings demonstrate that ADT significantly reduces pulmonary TMPRSS2 expression, with direct AR antagonists showing the strongest effect. This suggests a potential mechanistic explanation for differential COVID-19 susceptibility and provides a rationale for investigating AR-targeted therapies as potential protective interventions against SARS-CoV-2 infection severity. Full article
(This article belongs to the Special Issue Molecular Research of Urological Diseases)
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18 pages, 2202 KB  
Article
Modulation of Piceatannol Skin Diffusion by Spilanthol and UV Filters: Insights from the Strat-M™ Model
by Gisláine C. da Silva, Rodney A. F. Rodrigues and Carla B. G. Bottoli
Dermato 2025, 5(4), 19; https://doi.org/10.3390/dermato5040019 - 7 Oct 2025
Viewed by 144
Abstract
Background: currently, there is a growing trend toward multifunctional cosmetics, which combine several active ingredients in a single product to enhance efficacy and user convenience. As ingredients may influence one another, it is important to study the behavior of mixing multiple compounds in [...] Read more.
Background: currently, there is a growing trend toward multifunctional cosmetics, which combine several active ingredients in a single product to enhance efficacy and user convenience. As ingredients may influence one another, it is important to study the behavior of mixing multiple compounds in complex formulations, especially regarding their interaction with the skin. Piceatannol, for instance, is a naturally occurring stilbene recognized for its in vitro potent antioxidant, anti-inflammatory, and anti-aging activities, making it a promising candidate for dermocosmetic use in suncare. But despite its beneficial biological activities, its cutaneous permeation remains poorly understood, particularly when delivered from complex formulations containing multiple ingredients. Objectives: in this sense, this study aimed to evaluate the in vitro skin diffusion profile of piceatannol from a passion fruit seed extract (Pext) incorporated into a topical base (Bem) or an organic sunscreen emulsion (Oem), with or without a spilanthol-rich Acmella oleracea extract (Jext) used as a natural permeation enhancer. Methods: due to ethical and variability issues with human and animal skins, the Strat-M™ synthetic membrane was chosen as a standardized model for the in vitro skin permeation assays. Piceatannol localization within membrane layers was examined by confocal Raman microscopy (CRM), while compound identification in donor and receptor compartments was performed via UHPLC-DAD. Results: piceatannol from Bem was detected up to 140 µm from the Strat-M™ surface and exceeded 180 µm in depth when Jext and organic sunscreens were included in the formulation. Notably, formulations containing Jext and those based on Oem promoted enhanced accumulation in both the stratum corneum and deeper skin layers, suggesting an improved delivery potential in lipid-rich vehicles. Conclusions: even though some instability issues were observed, piceatannol penetration into Strat-M™ from the proposed formulations was confirmed, and the results provide a foundation for further research on its topical delivery, supporting the rational development of formulations capable of harnessing its demonstrated biological properties. Full article
(This article belongs to the Special Issue Systemic Photoprotection: New Insights and Novel Approaches)
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12 pages, 2063 KB  
Case Report
Necrotizing Enterocolitis Due to Mesenteric Artery Thrombosis in a Patient with Craniofrontonasal Dysplasia: Casual or Causal Association?
by Gregorio Serra, Deborah Bacile, Maria Rita Di Pace, Alessandra Giliberti, Mario Giuffré, Marco Pensabene, Giusy Ranucci, Maria Sergio, Giovanni Corsello and Rosaria Nardello
J. Clin. Med. 2025, 14(19), 7055; https://doi.org/10.3390/jcm14197055 - 6 Oct 2025
Viewed by 280
Abstract
Background: Craniofrontonasal dysplasia (CFND) is an X-linked developmental disorder caused by mutations in the EFNB1 gene located on chromosome Xq13. This gene encodes ephrin-B1, a ligand for Eph receptors, which is involved in cell signaling pathways and the development of the nervous [...] Read more.
Background: Craniofrontonasal dysplasia (CFND) is an X-linked developmental disorder caused by mutations in the EFNB1 gene located on chromosome Xq13. This gene encodes ephrin-B1, a ligand for Eph receptors, which is involved in cell signaling pathways and the development of the nervous and vascular systems, as well as facial and cranial structures. Paradoxically, the syndrome manifests with greater severity in heterozygous females, whereas hemizygous males typically present with mild or no abnormalities. Methods and Results: We report the case of a late preterm female neonate with dysmorphic features at birth, who subsequently developed necrotizing enterocolitis (NEC) caused by thrombosis of the superior mesenteric artery. Extensive bowel resection led to short bowel syndrome, resulting in cholestatic liver disease, malabsorption, and growth impairment. Array-comparative genomic hybridization (a-CGH) analysis identified a ~791 Kb microduplication at Xq13.1, encompassing the EFNB1 gene, confirming the diagnosis of CFND. She was enrolled in a multidisciplinary follow-up program and, at 2 years of age, presents with marked growth and neurodevelopmental delay. Conclusions: This report describes a rare association between CFND and NEC caused by superior mesenteric artery thrombosis. To the best of our knowledge, no previously reported cases of CFND associated with thrombosis or thrombosis-related conditions, including NEC, have been identified. This is based on a literature review (2004–2025) performed using PubMed and Scopus, and limited to English-language case reports and reviews. Full article
(This article belongs to the Section Clinical Pediatrics)
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12 pages, 601 KB  
Article
Oncotype DX Recurrence Score Predicts Survival in Invasive Micropapillary Breast Carcinoma: A National Cancer Database Analysis
by Ali J. Haider, Mohummad Kazmi, Kyle Chang, Waqar M. Haque, Efstathia Polychronopoulou, Jonathon S. Cummock, Sandra S. Hatch, Andrew M. Farach, Upendra Parvathaneni, E. Brian Butler and Bin S. Teh
Curr. Oncol. 2025, 32(10), 559; https://doi.org/10.3390/curroncol32100559 - 5 Oct 2025
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Abstract
(1) Background: Invasive micropapillary carcinoma (IMPC) is a rare, aggressive breast cancer subtype marked by high lymph node metastasis rates. While Oncotype DX recurrence score (RS) offers prognostic information for patients with hormone-receptor-positive (HR+) breast cancer, its utility in IMPC—a histology with distinct [...] Read more.
(1) Background: Invasive micropapillary carcinoma (IMPC) is a rare, aggressive breast cancer subtype marked by high lymph node metastasis rates. While Oncotype DX recurrence score (RS) offers prognostic information for patients with hormone-receptor-positive (HR+) breast cancer, its utility in IMPC—a histology with distinct biologic behavior—remains unvalidated. This study evaluates whether Oncotype DX offers prognostic information with respect to overall survival (OS) in non-metastatic, early-stage patients with IMPC of the breast. (2) Methods: The National Cancer Database (2004–2020) was queried to select for women with ER+/HER2−, T1-T2N0-N1 IMPC who underwent Oncotype DX testing and received no neoadjuvant therapy. Patients were stratified by RS: low (≤11), intermediate (12–25), and high (>25). Kaplan–Meier survival curves and log-rank tests compared 5-year OS between groups. Multivariable Cox proportional hazards models assessed RS as an independent predictor, adjusting for age, race, comorbidities, grade, radiation, and insurance status. (3) Results: A total of 1325 women met the selection criteria. The cohort demonstrated significant survival disparities by RS (log-rank p = 0.017). Five-year OS rates were 97.5%, 97.5%, and 93.7% for low, intermediate, and high-risk patients, respectively. Adjusted multivariate analysis confirmed RS as an independent prognosticator: low (HR = 0.31, 95% CI: 0.15–0.75) and intermediate (HR = 0.32, 95% CI: 0.15–0.75) scores correlated with reduced mortality versus high RS. Omission of radiation therapy (HR = 2.68, 95% CI: 1.05–6.86) and higher comorbidity burden (0 comorbidities vs. ≥2: HR = 0.25, 95% CI: 0.10–0.61) were significantly associated with worse survival. (4) Conclusions: Oncotype DX is predictive for OS in IMPC, with high RS (>25) portending poorer outcomes. The survival detriment associated with RT omission aligns with prior studies demonstrating RT benefit in higher-risk cohorts. These findings validate RS as a prognostic tool in IMPC and underscore its potential to refine adjuvant therapy, particularly RT utilization. Future studies should explore RS-driven treatment personalization in IMPC, including comorbidity management and adjuvant radiation to improve outcomes in this distinct patient population. Full article
(This article belongs to the Section Breast Cancer)
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17 pages, 2779 KB  
Article
Self-Reported Outcomes of Endocrine Therapy with or Without Ovarian Suppression in Premenopausal Breast Cancer Patients: A Brazilian Quality-of-Life Prospective Cohort
by Natália Nunes, Giselle Carvalho, Bernardo Ramos, Juliana Pecoraro, Lilian Lerner, Debora Azevedo, Thamirez Ferreira, Larissa Santiago de Moura, Carolina Galvão and Mariana Monteiro
Cancers 2025, 17(19), 3229; https://doi.org/10.3390/cancers17193229 - 4 Oct 2025
Viewed by 435
Abstract
Background: Endocrine therapy (ET) with or without ovarian function suppression (OFS) is a cornerstone treatment for estrogen receptor-positive (ER+) breast cancer (BC) in premenopausal women, but its impact on quality of life (QoL) and sexual health remains a concern. Methods: We conducted a [...] Read more.
Background: Endocrine therapy (ET) with or without ovarian function suppression (OFS) is a cornerstone treatment for estrogen receptor-positive (ER+) breast cancer (BC) in premenopausal women, but its impact on quality of life (QoL) and sexual health remains a concern. Methods: We conducted a multicenter, prospective, observational study including premenopausal women (≤50 years) diagnosed with stage I–III ER+ BC and treated in private healthcare facilities in Brazil between 2013 and 2023. Patients received ET alone (ET-only) or combined with OFS (OFS-ET). QoL was assessed at baseline and 3, 6, 9, 12, and 24 months using the EORTC QLQ-BR23. Sexual functioning and sexual enjoyment were prespecified primary outcomes. Logistic regression identified factors associated with OFS use, and Fisher’s exact test was applied for categorical comparisons at 24 months. Results: Among 363 patients (80% ET-only, 20% ET + OFS), younger age, advanced stage, and chemotherapy were independently associated with OFS use. Both groups reported early declines in sexual functioning and enjoyment. By 24 months, ET-only patients had returned to baseline, whereas OFS patients remained below baseline. At the item level, no significant differences were observed in sexual desire (51.5% vs. 42.0%; p = 0.33) or enjoyment (26.0% vs. 13.5%; p = 0.20). Lack of sexual activity was more frequent in the OFS group (60.6% vs. 41.2%; p = 0.05). Body image was significantly more impaired with OFS, with a higher proportion of patients reporting feeling less attractive (38.2% vs. 19.9%; p = 0.04) and less feminine (26.5% vs. 11.7%; p = 0.05). Conclusions: ET impairs sexual health in young BC survivors, particularly when combined with OFS. These findings underscore the need for routine sexual health assessments and supportive interventions in survivorship care. Full article
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