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24 pages, 1661 KB  
Review
Molecular Prognosticators Guiding Fertility-Sparing Surgery in Early-Stage Endometrial Cancer: A Comprehensive Review
by Saniyah Shaikh, Salsabil Haque, Hafsah Tajammul Khalifey, Halla Anas Samour, Ayesha Deed, Rutaba Mahereen, Noor Nabiha, Safwaan Shaikh, Lara M. Samhan, Mohammed Imran Khan and Ahmed Yaqinuddin
Cancers 2025, 17(22), 3602; https://doi.org/10.3390/cancers17223602 - 7 Nov 2025
Viewed by 118
Abstract
Background: Endometrial cancer (EC) is a common malignancy found among women. It is ranked as the 6th most common cancer among women and the 15th most common cancer globally. Increasing prevalence of several factors like obesity and other metabolic disorders have caused a [...] Read more.
Background: Endometrial cancer (EC) is a common malignancy found among women. It is ranked as the 6th most common cancer among women and the 15th most common cancer globally. Increasing prevalence of several factors like obesity and other metabolic disorders have caused a growing trend of prevalence of endometrial cancer. The standard approach of treatment with excellent prognosis is total hysterectomy with bilateral salpingo-oophorectomy (TH/BSO). However, due to its drawback of complete infertility, newer approaches of fertility-sparing approaches are emerging to combat this challenge. Clinicians must choose the most suitable candidates for fertility-sparing surgery (FSS) using the present existing conventional criteria with regard to the patient’s age, tumor characteristics, and fertility goals. The limitations using the conventional criteria can be eliminated by refining the criteria with molecular prognostic factors to ease the candidate selection process for FSS. Methods: Relevant literature regarding molecular subtypes, hormone therapy sensitivity, clinical assessment, and guidelines pertaining to fertility preservation in EC were retrieved from several electronic databases and articles addressing the role of molecular profiling in predicting patient response, guiding patient selection, and/or informing the development of therapies for fertility preservation in early-stage EC, particularly in women of reproductive age were included. Primary focus was on areas of consensus, emerging trends, and evidence gaps that warrant further investigation. This review will assess the integration of molecular prognostic factors to refine the patient selection criteria and guide FSS in early-stage EC. We will present existing clinical criteria, ongoing clinical trials, limitations, and the advantages of integrating molecular data on patient selection, treatment safety, and fertility outcomes. Results: Four distinct molecular subtypes have been classified which includes POLE-mut, MMR-d, p53-abn and NSMP. POLE-mut subtype had excellent prognosis with >95% patients achieving complete remission with <2% recurrence rate followed by MMRd and NSMP with intermediate prognosis and lastly p53-abn with poor prognosis of 60–70% achieving complete remission and 30–40% having recurrence. The data highlights the clinical value of molecular classification in selecting appropriate candidates for fertility sparing surgery (FSS). Conclusions: There is a lack of integration of molecular subtypes for clinicians to choose candidates for FSS and this gap should be addressed. Further research must be performed to follow personalized medicine to refine their treatment plan. Full article
(This article belongs to the Special Issue Endometrial Cancer Therapy: Foundations and Future Directions)
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14 pages, 581 KB  
Review
Surgical Ovarian Suppression and Breast Cancer—What Do We Know About It?
by Angel Yordanov, Ihsan Hasan, Mariela Vasileva-Slaveva, Eva Tsoneva, Stoyan Kostov and Vesselina Yanachkova
Medicina 2025, 61(11), 1905; https://doi.org/10.3390/medicina61111905 - 24 Oct 2025
Viewed by 420
Abstract
Breast cancer (BC) is the most common malignancy in women worldwide, with incidence projected to rise, particularly among younger patients. In premenopausal women with hormone receptor-positive disease, ovarian suppression is an established component of systemic therapy, most often achieved pharmacologically with gonadotropin-releasing hormone [...] Read more.
Breast cancer (BC) is the most common malignancy in women worldwide, with incidence projected to rise, particularly among younger patients. In premenopausal women with hormone receptor-positive disease, ovarian suppression is an established component of systemic therapy, most often achieved pharmacologically with gonadotropin-releasing hormone agonists (GnRHas). Bilateral salpingo-oophorectomy (BSO) represents a surgical alternative that ensures definitive suppression, eliminates compliance issues, and is more cost-effective in the long term. Despite these advantages, BSO induces irreversible menopause, associated with vasomotor symptoms, cardiovascular morbidity, bone loss, cognitive decline, and reduced quality of life. Evidence suggests that BSO is most appropriate in selected cases, including women unable to tolerate or adhere to medical suppression, those with inadequate estradiol suppression, patients approaching natural menopause, individuals with metastatic hormone receptor-positive disease, and carriers of BRCA1 mutations, especially with triple-negative tumors. Conversely, data on its benefit in BRCA2 carriers remain limited. Overall, BSO provides oncologic outcomes comparable to medical suppression but at the cost of permanent systemic effects. The decision between surgical and medical ovarian suppression should be individualized, balancing oncologic efficacy, comorbidities, genetic background, and patient preference. Further studies are needed to define the optimal duration of medical suppression and clarify the role of BSO in hereditary breast cancer. Full article
(This article belongs to the Section Obstetrics and Gynecology)
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24 pages, 2782 KB  
Article
Optimization of Electricity–Carbon Coordinated Scheduling Process for Virtual Power Plants Based on an Improved Snow Ablation Optimizer Algorithm
by Haiji Wang, Ming Zeng, Xueying Lu, Zhijian Chen and Jiankun Hu
Processes 2025, 13(9), 3027; https://doi.org/10.3390/pr13093027 - 22 Sep 2025
Viewed by 369
Abstract
Given the strong coupling between electricity flow and carbon flow, promoting the low-carbon transformation of the energy sector is a crucial measure to actively responding to climate challenges. As a pivotal hub linking the electricity market with the carbon market, promoting electricity–carbon coordinated [...] Read more.
Given the strong coupling between electricity flow and carbon flow, promoting the low-carbon transformation of the energy sector is a crucial measure to actively responding to climate challenges. As a pivotal hub linking the electricity market with the carbon market, promoting electricity–carbon coordinated scheduling of Virtual Power Plants (VPPs) is of great significance in expediting the energy transition process. Based on the introduction of carbon potential, this manuscript constructs a VPP electricity–carbon coordinated scheduling model that incorporates various typical elements, including renewable energy units and demand response. Furthermore, this paper utilizes Brain Storm Optimization (BSO) to improve the Snow Ablation Optimizer (SAO) algorithm and applies the improved algorithm to solve the model developed in this manuscript. Finally, an analysis was conducted using a small-scale VPP project in eastern China, and the results are the following: Firstly, the SAO improved by BSO demonstrates a significant enhancement in solution efficiency. In particular, for the cases presented in this manuscript, the algorithm’s convergence speed increased by 42.85%. Secondly, under the multi-market conditions and with real-time carbon potential, VPPs will possess greater flexibility in scheduling optimization and stronger incentives to fully explore their emission reduction potential through collaborative electricity–carbon scheduling, thereby improving both economic and environmental performance. However, constrained by factors such as the currently low carbon price level, the extent of improvement in VPPs’ performance under real-time carbon potential, compared to fixed carbon potential, remains relatively limited, with a 1.07% increase in economic benefits and a 2.63% reduction in carbon emissions. Thirdly, an increase in carbon prices can incentivize VPPs to continuously tap into their emission reduction potential, but beyond a certain threshold (120 CNY/t in this case study), the marginal contribution of further carbon price increases to emission reductions will progressively decline. Specifically, for every 20-yuan increase in the carbon price, the carbon emission reduction rate of VPPs drops below 1%. Full article
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18 pages, 1425 KB  
Article
Blackberry (Rubus spp. Xavante Cultivar) Oil-Loaded PCL Nanocapsules: Sustainable Bioactive for In Vitro Collagen-Boosting Skincare
by Daniela F. Maluf, Brenda A. Lopes, Mariana D. Miranda, Luana C. Teixeira, Ana P. Horacio, Amanda Jansen, Madeline S. Correa, Guilherme dos Anjos Camargo, Jessica Mendes Nadal, Jane Manfron, Patrícia M. Döll-Boscardin and Paulo Vitor Farago
Cosmetics 2025, 12(4), 159; https://doi.org/10.3390/cosmetics12040159 - 25 Jul 2025
Viewed by 1215
Abstract
Background: Blackberry seed oil (BSO), obtained from Rubus spp. Xavante cultivar via supercritical CO2 extraction, contains bioactive lipids and antioxidants, but its cosmetic application is limited by poor solubility and stability. Nanoencapsulation with poly(ε-caprolactone) (PCL) can overcome these limitations. Methods: BSO was [...] Read more.
Background: Blackberry seed oil (BSO), obtained from Rubus spp. Xavante cultivar via supercritical CO2 extraction, contains bioactive lipids and antioxidants, but its cosmetic application is limited by poor solubility and stability. Nanoencapsulation with poly(ε-caprolactone) (PCL) can overcome these limitations. Methods: BSO was characterized by Ultra-High-Performance Liquid Chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry and incorporated into PCL nanocapsules (NCBSO) using the preformed polymer deposition method. Physicochemical properties, stability (at 4 °C, room temperature, and 37 °C for 90 days), cytotoxicity, and collagen production were assessed in human fibroblasts. Additionally, a predictive in silico analysis using PASS Online, Molinspiration, and SEA platforms was performed to identify the bioactivities of major BSO compounds related to collagen synthesis, antioxidant potential, and anti-aging effects. Results: NCBSO showed a nanometric size of ~267 nm, low polydispersity (PDI < 0.2), negative zeta potential (−28 mV), and spherical morphology confirmed by FE-SEM. The dispersion remained stable across all tested temperatures, preserving pH and colloidal properties. In particular, BSO and NCBSO at 100 µg.mL−1 significantly enhanced in vitro collagen production by 170% and 200%, respectively, compared to untreated cells (p < 0.01). Superior bioactivity was observed for NCBSO. The in silico results support the role of key compounds in promoting collagen biosynthesis and protecting skin structure. No cytotoxic effects were achieved. Conclusions: The nanoencapsulation of BSO into PCL nanocapsules ensured formulation stability and potentiated collagen production. These findings support the potential of NCBSO as a promising candidate for future development as a collagen-boosting cosmeceutical. Full article
(This article belongs to the Special Issue Advanced Cosmetic Sciences: Sustainability in Materials and Processes)
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18 pages, 4646 KB  
Review
Endometrial Stromal Sarcoma: An Update
by Giulio Ricotta, Silvio Andrea Russo, Anna Fagotti, Alejandra Martinez, Elodie Gauroy, Mathilde Del, Valentin Thibaud, Bataillon Guillaume and Gwenaël Ferron
Cancers 2025, 17(11), 1893; https://doi.org/10.3390/cancers17111893 - 5 Jun 2025
Cited by 3 | Viewed by 4698
Abstract
Endometrial stromal sarcoma (ESS) is a rare malignant tumor of uterine mesenchyme, accounting for 15–20% of uterine sarcomas. It is classified into low-grade (LG-ESS) and high-grade (HG-ESS) subtypes, each defined by distinct histopathological and molecular features. LG-ESS exhibits slow progression, resembling proliferative-phase endometrial [...] Read more.
Endometrial stromal sarcoma (ESS) is a rare malignant tumor of uterine mesenchyme, accounting for 15–20% of uterine sarcomas. It is classified into low-grade (LG-ESS) and high-grade (HG-ESS) subtypes, each defined by distinct histopathological and molecular features. LG-ESS exhibits slow progression, resembling proliferative-phase endometrial stroma, with genetic alterations like JAZF1-SUZ12 fusions. HG-ESS is more aggressive, characterized by high mitotic activity, necrosis, and genetic markers such as BCOR internal tandem duplication, often leading to advanced-stage diagnosis. Surgical resection is the cornerstone for managing early-stage ESS. A total hysterectomy with bilateral salpingo-oophorectomy (BSO) is recommended to prevent recurrence. Fertility-preserving approaches may be considered in LG-ESS but are associated with high recurrence rates. Lymphadenectomy is not routinely performed, given its limited prognostic value. HG-ESS, due to its aggressiveness, often requires additional treatment, including chemotherapy. Adjuvant therapy varies by subtype. LG-ESS responds well to hormonal treatments such as aromatase inhibitors and progestins, while tamoxifen is contraindicated. HG-ESS, lacking hormonal receptor expression, is managed with chemotherapy, often incorporating doxorubicin-based regimens. Radiotherapy may improve local control in select cases but shows limited impact on overall survival. Advanced-stage ESS treatment focuses on complete cytoreduction, supplemented by systemic therapies. Hormonal therapy remains the standard for advanced LG-ESS, whereas HG-ESS relies on chemotherapy. Prognosis depends on the subtype and stage. LG-ESS has favorable outcomes, with five-year survival exceeding 90% in early stages, but recurrent disease remains common. HG-ESS is associated with poorer survival due to its aggressive nature. Advances in molecular profiling offer promising avenues for personalized therapies, integrating genomic insights with targeted treatments to improve outcomes in this rare malignancy. Full article
(This article belongs to the Special Issue Diagnosis, Staging, and Management for Gynecologic Oncology)
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26 pages, 592 KB  
Article
Hybrid Clustering-Enhanced Brain Storm Optimization Algorithm for Efficient Multi-Robot Path Planning
by Guangping Qiu, Jizhong Deng, Jincan Li and Weixing Wang
Biomimetics 2025, 10(6), 347; https://doi.org/10.3390/biomimetics10060347 - 26 May 2025
Cited by 3 | Viewed by 750
Abstract
To address the core challenges in multi-robot path planning (MRPP) within large-scale, complex environments—namely path conflicts, suboptimal task allocation, and computational inefficiency—this paper introduces a Hybrid Clustering-Enhanced Brain Storm Optimization (HC-BSO) algorithm designed to improve both path quality and computational efficiency significantly. For [...] Read more.
To address the core challenges in multi-robot path planning (MRPP) within large-scale, complex environments—namely path conflicts, suboptimal task allocation, and computational inefficiency—this paper introduces a Hybrid Clustering-Enhanced Brain Storm Optimization (HC-BSO) algorithm designed to improve both path quality and computational efficiency significantly. For optimizing initial task assignment, the conventional K-Means clustering method is supplanted by a hybrid clustering methodology that integrates Mini-Batch K-Means with Density-Based Spatial Clustering of Applications with Noise (DBSCAN), facilitating an efficient and robust partitioning of task points. Concurrently, we incorporate a two-stage exploration–perturbation evolutionary strategy. This strategy effectively balances global exploration with local exploitation, thereby enhancing solution diversity and search depth. Comparative analyses against the standard Brain Storm Optimization (BSO) and other prominent swarm intelligence algorithms reveal that HC-BSO exhibits significant advantages in terms of total path length, computational time, and path conflict avoidance. Notably, in large-scale, multi-task scenarios, HC-BSO consistently generates high-quality, conflict-free paths, demonstrating superior stability, convergence, and scalability. Full article
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20 pages, 2161 KB  
Article
Persistent Monocytic Bioenergetic Impairment and Mitochondrial DNA Damage in PASC Patients with Cardiovascular Complications
by Dilvin Semo, Zornitsa Shomanova, Jürgen Sindermann, Michael Mohr, Georg Evers, Lukas J. Motloch, Holger Reinecke, Rinesh Godfrey and Rudin Pistulli
Int. J. Mol. Sci. 2025, 26(10), 4562; https://doi.org/10.3390/ijms26104562 - 9 May 2025
Cited by 3 | Viewed by 3912
Abstract
Cardiovascular complications are a hallmark of Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (PASC), yet the mechanisms driving persistent cardiac dysfunction remain poorly understood. Emerging evidence implicates mitochondrial dysfunction in immune cells as a key contributor. This study investigated [...] Read more.
Cardiovascular complications are a hallmark of Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (PASC), yet the mechanisms driving persistent cardiac dysfunction remain poorly understood. Emerging evidence implicates mitochondrial dysfunction in immune cells as a key contributor. This study investigated whether CD14++ monocytes from long COVID patients exhibit bioenergetic impairment, mitochondrial DNA (mtDNA) damage, and defective oxidative stress adaptation, which may underlie cardiovascular symptoms in PASC. CD14++ monocytes were isolated from 14 long COVID patients with cardiovascular symptoms (e.g., dyspnea, angina) and 10 age-matched controls with similar cardiovascular risk profiles. Mitochondrial function was assessed using a Seahorse Agilent Analyzer under basal conditions and after oxidative stress induction with buthionine sulfoximine (BSO). Mitochondrial membrane potential was measured via Tetramethylrhodamine Ethyl Ester (TMRE) assay, mtDNA integrity via qPCR, and reactive oxygen species (ROS) dynamics via Fluorescence-Activated Cell Sorting (FACS). Parallel experiments exposed healthy monocytes to SARS-CoV-2 spike protein to evaluate direct viral effects. CD14++ monocytes from long COVID patients with cardiovascular symptoms (n = 14) exhibited profound mitochondrial dysfunction compared to age-matched controls (n = 10). Under oxidative stress induced by buthionine sulfoximine (BSO), long COVID monocytes failed to upregulate basal respiration (9.5 vs. 30.4 pmol/min in controls, p = 0.0043), showed a 65% reduction in maximal respiration (p = 0.4035, ns) and demonstrated a 70% loss of spare respiratory capacity (p = 0.4143, ns) with significantly impaired adaptation to BSO challenge (long COVID + BSO: 9.9 vs. control + BSO: 54 pmol/min, p = 0.0091). Proton leak, a protective mechanism against ROS overproduction, was blunted in long COVID monocytes (3-fold vs. 13-fold elevation in controls, p = 0.0294). Paradoxically, long COVID monocytes showed reduced ROS accumulation after BSO treatment (6% decrease vs. 1.2-fold increase in controls, p = 0.0015) and elevated mitochondrial membrane potential (157 vs. 113.7 TMRE fluorescence, p = 0.0179), which remained stable under oxidative stress. mtDNA analysis revealed severe depletion (80% reduction, p < 0.001) and region-specific damage, with 75% and 70% reductions in amplification efficiency for regions C and D (p < 0.05), respectively. In contrast, exposure of healthy monocytes to SARS-CoV-2 spike protein did not recapitulate these defects, with preserved basal respiration, ATP production, and spare respiratory capacity, though coupling efficiency under oxidative stress was reduced (p < 0.05). These findings suggest that mitochondrial dysfunction in long COVID syndrome arises from maladaptive host responses rather than direct viral toxicity, characterized by bioenergetic failure, impaired stress adaptation, and mitochondrial genomic instability. This study identifies persistent mitochondrial dysfunction in long COVID monocytes as a critical driver of cardiovascular complications in PASC. Key defects—bioenergetic failure, impaired stress adaptation and mtDNA damage—correlate with clinical symptoms like heart failure and exercise intolerance. The stable elevation of mitochondrial membrane potential and resistance to ROS induction suggest maladaptive remodeling of mitochondrial physiology. These findings position mitochondrial resilience as a therapeutic target, with potential strategies including antioxidants, mtDNA repair agents or metabolic modulators. The dissociation between spike protein exposure and mitochondrial dysfunction highlights the need to explore host-directed mechanisms in PASC pathophysiology. This work advances our understanding of long COVID cardiovascular sequelae and provides a foundation for biomarker development and targeted interventions to mitigate long-term morbidity. Full article
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11 pages, 563 KB  
Article
A Regional Experience of Adult Granulosa Cell Tumours: A Retrospective Analysis
by Joanne Moffatt, Jo Morrison, Srividya Sundararajan, Rebecca Newhouse, Laura Atherton, Jonathan Frost, Philip Rolland, Kirsty Milford, Katharine Edey, Jane Borley, Amy Sanders, Axel Walther and Claire Newton
Onco 2025, 5(2), 20; https://doi.org/10.3390/onco5020020 - 1 May 2025
Viewed by 1206
Abstract
Background: Adult granulosa cell tumours (AGCT) of the ovary account for 2–5% of ovarian tumours, with 30% occurring in women of childbearing age. Despite a good prognosis, up to 25% recur. There is a paucity of high-quality evidence to guide management. Objective: To [...] Read more.
Background: Adult granulosa cell tumours (AGCT) of the ovary account for 2–5% of ovarian tumours, with 30% occurring in women of childbearing age. Despite a good prognosis, up to 25% recur. There is a paucity of high-quality evidence to guide management. Objective: To describe management of AGCT across multiple gynaecological cancer centres. Methods: Retrospective analysis of electronic patient records from six gynaecological cancer centres in Southwest England between 2000 and 2021 (n = 119). Results: We included 107 patients with a median follow-up of 60 months (0–261 months). Most (97/107; 90.7%) were diagnosed with stage I disease (31.8% stage Ic). Primary management was staging surgery in 33/107 (30.8%), hysterectomy and bilateral salpingo-oophorectomy (BSO) (28/107; 26.2%), or conservation of an ovary (17/107; 15.9%). Three had a subsequent pregnancy. A quarter (27/107; 25.2%) were diagnosed with recurrent disease. Fifteen patients (15/107; 14%) had multiple recurrences. Recurrence was more likely if cyst rupture was reported at surgery (38.7%) compared with no rupture (14.3%; p < 0.001). The recurrence rate was higher with ovarian conservation (6/17; 35.3%) compared with BSO (21/90; 23.3%; p < 0.01), and all recurrences involved the residual ovary. Of the 11 deaths, 6 (54.5%) were attributed to progressive disease. Conclusions: Although survival with early-stage disease is good, ovarian cystectomy or unilateral ovarian conservation was associated with increased risk of recurrence. There is no conclusive evidence to support a contralateral oophorectomy in pre-menopausal women, but completion surgery should at least be considered, either immediately or after childbearing/assisted reproductive treatment. Full article
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12 pages, 1608 KB  
Article
Sm3+-Doped Bismuth(III) Oxosilicate (Bi4Si3O12:Sm3+): A Study of Crystal Structure and Mulliken Charges
by Yan Zhang, Xuefeng Xiao, Yan Huang, Jiashun Si, Shuaijie Liang, Qingyan Xu, Huan Zhang, Lingling Ma, Cui Yang, Tianyong Ma, Xuefeng Zhang, Jiayue Xu, Tian Tian and Hui Shen
Crystals 2025, 15(5), 423; https://doi.org/10.3390/cryst15050423 - 30 Apr 2025
Viewed by 568
Abstract
In this paper, using the Materials Studio software (version 2020) and based on first-principles and density functional theory, the effects of Sm3+ doping at different ratios (1/12, 1/6, and 1/3) on the crystal structure and Mulliken charge distribution of bismuth silicate (Bi [...] Read more.
In this paper, using the Materials Studio software (version 2020) and based on first-principles and density functional theory, the effects of Sm3+ doping at different ratios (1/12, 1/6, and 1/3) on the crystal structure and Mulliken charge distribution of bismuth silicate (Bi4Si3O12, BSO) were analyzed. The examination of the crystal framework and Mulliken charge allocation reveals that increasing levels of Sm3+ doping have the potential to warp the lattice’s symmetry and result in a decrease in electrical conductivity. With the rise in the concentration of Sm3+ doping, the Sm-O bond length shows a pattern of a rise at first and then a fall, demonstrating that electrons are shared, and reaches its minimum length with a doping proportion of 1/12. At the same time, when the doping concentration of Sm3+ rises, the Bi-O bond length becomes longer; it reaches its shortest length when the doping concentration is 1/12. This finding suggests that when a small quantity of Sm3+ is doped, especially when the doping concentration is 1/12, the covalent nature of the bonds between Sm-O and Bi-O atoms within the BSO crystal is strengthened. Full article
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15 pages, 3066 KB  
Article
Vasodilatory Effect of n-Butanol Extract from Sanguisorba officinalis L. and Its Mechanism
by Hangyu Jin, Jiaze Li, Shuyuan Wang, Enyi Jin, Jun Zhe Min, Gao Li, Yun Jung Lee and Lihua Cao
Plants 2025, 14(7), 1095; https://doi.org/10.3390/plants14071095 - 1 Apr 2025
Viewed by 881
Abstract
The dried root of Sanguisorba officinalis L. (commonly known as Diyu) has been studied for its various pharmacological effects, including its antibacterial, antitumor, antioxidant, and anti-inflammatory activities. In the present study, primary cultured vascular endothelial cells (HUVECs) and isolated phenylephrine-precontracted rat thoracic aortic [...] Read more.
The dried root of Sanguisorba officinalis L. (commonly known as Diyu) has been studied for its various pharmacological effects, including its antibacterial, antitumor, antioxidant, and anti-inflammatory activities. In the present study, primary cultured vascular endothelial cells (HUVECs) and isolated phenylephrine-precontracted rat thoracic aortic rings were examined to investigate the possible mechanism of a butanol extract of Diyu (BSO) in its vascular relaxant effect. HUVECs treated with BSO produced a significantly higher amount of nitric oxide (NO) compared to the control. However, its production was inhibited by pretreatment with NG-nitro-L-arginine methylester (L-NAME) or wortmannin. BSO also increased the phosphorylation levels of endothelial nitric oxide synthase (eNOS) and Akt. In the aortic ring, BSO relaxed PE-precontracted rat thoracic aortic rings in a concentration-dependent manner. The absence of the vascular endothelium significantly attenuated BSO-induced vasorelaxation. The non-selective NOS inhibitor, L-NAME, and the selective inhibitor of soluble guanylyl cyclase (sGC), 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ), dramatically inhibited the BSO-induced relaxation effect of the endothelium-intact aortic ring. Ca2+-free buffer and intracellular Ca2+ homeostasis regulators (TG, Gd3+, and 2–APB) inhibited BSO-induced vasorelaxation. In Ca2+-free Krebs solution, BSO markedly reduced PE-induced contraction. Vasodilation induced by BSO was significantly inhibited by wortmannin, an inhibitor of Akt. Pretreatment with the non-selective inhibitor of Ca2+-activated K+ channels (KCa), tetraethylammonium (TEA), significantly attenuated the BSO-induced vasorelaxant effect. Furthermore, BSO decreased the systolic blood pressure and heart rate in a concentration-dependent manner in rats. In conclusion, BSO induces vasorelaxation via endothelium-dependent signaling, primarily through the activation of the PI3K-Akt-eNOS-NO signaling pathway in endothelial cells, and the activation of the NO-sGC-cGMP-K⁺ channels pathway in vascular smooth muscle cells. Additionally, store-operated Ca2+ entry (SOCE)-eNOS pathways and the inhibition of Ca2⁺ mobilization from intracellular stores contribute to BSO-induced vasorelaxation. Full article
(This article belongs to the Special Issue Ethnobotanical and Pharmacological Study of Medicinal Plants)
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29 pages, 4913 KB  
Review
Comparative B3PW and B3LYP Calculations of ABO3 (A = Ba, Sr, Pb, Ca; B = Sn, Ti, Zr) Neutral (001) and Polar (111) Surfaces
by Roberts I. Eglitis, Juris Purans, Ran Jia, Sergei P. Kruchinin and Steffen Wirth
Inorganics 2025, 13(4), 100; https://doi.org/10.3390/inorganics13040100 - 23 Mar 2025
Cited by 12 | Viewed by 1448
Abstract
We completed B3LYP and B3PW computations for AO- and BO2-terminated (001) as well as AO3- and B-terminated (111) surfaces of BSO, BTO, STO, PTO, CTO, BZO, SZO, and CZO perovskites. In particular, we performed the first B3LYP computations for [...] Read more.
We completed B3LYP and B3PW computations for AO- and BO2-terminated (001) as well as AO3- and B-terminated (111) surfaces of BSO, BTO, STO, PTO, CTO, BZO, SZO, and CZO perovskites. In particular, we performed the first B3LYP computations for polar BSO (111) surfaces. We observed that most of the upper-layer atoms for AO- and BO2-terminated ABO perovskite (001) surfaces relax inward. In contrast, practically all second-layer atoms relax upward. Lastly, almost all third-layer atoms relax inward. This tendency is less pronounced for atomic relaxation of first, second, and third layer atoms for AO3- and B-terminated ABO perovskite (111) surfaces. For almost all ABO perovskites, their (001) surface rumplings s are considerably larger for AO-terminated compared to BO2-terminated surfaces. On the contrary, the ABO perovskite (001) surface energies, for both AO and BO2-terminations, are essentially equivalent. The ABO perovskite polar (111) surface energies are always substantially larger than their neutral (001) surface energies. In most cases, the surface energies of AO3-terminated ABO perovskite polar (111) surfaces are considerably larger than their B-terminated surface energies. Our computations illustrate a noticeable boost in the B-O bond covalency near the BO2-terminated (001) surface related to the bulk. Our computed ABO perovskite bulk Γ-Γ band gaps are almost always reduced near the AO- and BO2-terminated neutral (001) surfaces as well as in most cases also near the AO3- and B-terminated polar (111) surfaces. Full article
(This article belongs to the Special Issue Optical and Quantum Electronics: Physics and Materials)
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16 pages, 4050 KB  
Article
First-Principles Calculations of the Optical Properties of Bi4Si3O12: RE (RE = Ho3+, Tb3+, Eu3+, Gd3+, Sm3+, Tm3+) Crystals
by Yan Huang, Xuefeng Xiao, Yunlong Zhang, Xu Han, Jiahao Li, Yan Zhang, Jiashun Si, Shuaijie Liang, Qingyan Xu, Huan Zhang, Lingling Ma, Cui Yang, Xuefeng Zhang, Jiayue Xu, Tian Tian and Hui Shen
Crystals 2025, 15(3), 232; https://doi.org/10.3390/cryst15030232 - 28 Feb 2025
Cited by 1 | Viewed by 661
Abstract
This study employs the first-principles calculation method based on density functional theory to investigate and analyze the effects of doping various rare earthions on the optical properties of bismuth silicate (Bi4Si3O12, BSO) crystals. The results indicate that [...] Read more.
This study employs the first-principles calculation method based on density functional theory to investigate and analyze the effects of doping various rare earthions on the optical properties of bismuth silicate (Bi4Si3O12, BSO) crystals. The results indicate that the electronic structure variations of rare earth ions significantly influence the electronic structure and transition characteristics of BSO crystals, thereby altering their optical properties. Specifically, Tm3+ doping notably enhances the polarization capability and infrared responsiveness of BSO crystals, Ho3+ doping improves their absorption and scattering abilities in the visible light range, while Eu3+ doping enhances their ultraviolet absorption. Overall, Tm3+ doping and Ho3+ doping exhibit the most prominent effects on the optical performance of BSO crystals, providing theoretical guidance for designing and optimizing BSO crystals with specific optical properties. Full article
(This article belongs to the Section Inorganic Crystalline Materials)
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22 pages, 3557 KB  
Article
Mitoregulin Promotes Cell Cycle Progression in Non-Small Cell Lung Cancer Cells
by Colleen S. Stein, Connor R. Linzer, Collin D. Heer, Nathan H. Witmer, Jesse D. Cochran, Douglas R. Spitz and Ryan L. Boudreau
Int. J. Mol. Sci. 2025, 26(5), 1939; https://doi.org/10.3390/ijms26051939 - 24 Feb 2025
Viewed by 1619
Abstract
Mitoregulin (MTLN) is a 56-amino-acid mitochondrial microprotein known to modulate mitochondrial energetics. MTLN gene expression is elevated broadly across most cancers and has been proposed as a prognostic biomarker for non-small cell lung cancer (NSCLC). In addition, lower MTLN expression in lung adenocarcinoma [...] Read more.
Mitoregulin (MTLN) is a 56-amino-acid mitochondrial microprotein known to modulate mitochondrial energetics. MTLN gene expression is elevated broadly across most cancers and has been proposed as a prognostic biomarker for non-small cell lung cancer (NSCLC). In addition, lower MTLN expression in lung adenocarcinoma (LUAD) correlates with significantly improved patient survival. In our studies, we have found that MTLN silencing in A549 NSCLC cells slowed proliferation and, in accordance with this, we observed the following: (1) increased proportion of cells in the G1 phase of cell cycle; (2) protein changes consistent with G1 arrest (e.g., reduced levels and/or reduced phosphorylation of ERK, MYC, CDK2, and RB, and elevated p27Kip1); (3) reduction in clonogenic cell survival and; (4) lower steady-state cytosolic and mitochondrial H2O2 levels as indicated by use of the roGFP2-Orp1 redox sensor. Conflicting with G1 arrest, we observed a boost in cyclin D1 abundance. We also tested MTLN silencing in combination with buthionine sulfoximine (BSO) and auranofin (AF), drugs that inhibit GSH synthesis and thioredoxin reductase, respectively, to elevate the reactive oxygen species (ROS) amount to a toxic range. Interestingly, clonogenic survival after drug treatment was greater for MTLN-silenced cultures versus the control cultures. Lower H2O2 output and reduced vulnerability to ROS damage due to G1 status may have jointly contributed to the partial BSO + AF resistance. Overall, our results provide evidence that MTLN fosters H2O2 signaling to propel G1/S transition and suggest MTLN silencing as a therapeutic strategy to limit NSCLC growth. Full article
(This article belongs to the Special Issue Role of Mitochondria in Cancer)
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18 pages, 4346 KB  
Article
Reactive Oxygen Species-Sensitive Nanophotosensitizers Composed of Buthionine Sulfoximine-Conjugated Chitosan Oligosaccharide for Enhanced Photodynamic Treatment of Cancer Cells
by Hyo Young Lee, Ji-Sun Park, Taeyu Grace Kim, Taeyeon Kim, Do Hoon Kim, Jejung Yun and Young-IL Jeong
Int. J. Mol. Sci. 2024, 25(23), 12609; https://doi.org/10.3390/ijms252312609 - 24 Nov 2024
Cited by 2 | Viewed by 1640
Abstract
The efficacy of photodynamic therapy (PDT) based on traditional photosensitizers is generally limited by the cellular redox homeostasis system due to the reactive oxygen species (ROS) scavenging effect of glutathione (GSH). In this study, buthionine sulfoximine (BSO), a GSH inhibitor, was conjugated with [...] Read more.
The efficacy of photodynamic therapy (PDT) based on traditional photosensitizers is generally limited by the cellular redox homeostasis system due to the reactive oxygen species (ROS) scavenging effect of glutathione (GSH). In this study, buthionine sulfoximine (BSO), a GSH inhibitor, was conjugated with the amine group of chitosan oligosaccharide (COS) using a thioketal linker (COSthBSO) to liberate BSO and chlorine e6 (Ce6) under oxidative stress, and then, Ce6-COSthBSO NP (Ce6-COSthBSO NP), fabricated by a dialysis procedure, showed an accelerated release rate of BSO and Ce6 by the addition of hydrogen peroxide, indicating that nanophotosensitizers have ROS sensitivity. In the in vitro cell culture study using HCT116 colon carcinoma cells, a combination of BSO and Ce6 efficiently suppressed the intracellular GSH and increased ROS production compared to the sole treatment of Ce6. In particular, Ce6-COSthBSO NP showed higher efficacy in the suppression of GSH levels and ROS production compared to the free Ce6 and Ce6/BSO combination. These results were due to the fact that Ce6-COSthBSO NP was efficiently delivered to the intracellular region, suppressed intracellular GSH levels, and elevated ROS levels. The in vivo animal tumor xenograft study demonstrated Ce6-COSthBSO NP being efficiently delivered to the tumor tissue, i.e., the fluorescence intensity in the tumor tissue was higher than those of other organs. The combination of Ce6 and BSO efficiently suppressed tumor growth compared to the sole treatment of Ce6, indicating that BSO might efficiently suppress GSH levels and increase ROS levels in the tumor microenvironment. Specifically, Ce6-COSthBSO NP showed the strongest performance in inhibition of tumor growth than those of Ce6 or the CE6/BSO combination, indicating that they were efficiently delivered to tumor tissue, increased ROS levels, and then efficiently inhibited tumor growth. We suggest that COSthBSO nanophotosensitizers are promising candidates for PDT treatment of cancer cells. Full article
(This article belongs to the Special Issue Photodynamic Therapy and Photodetection, 2nd Edition)
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17 pages, 3196 KB  
Article
Comparative Study of Injected Alzheimer’s Disease Models in Rats: Insights from Experimental Research
by Hanane Doumar, Hicham El Mostafi, Aboubaker Elhessni, Abderrahim Laaziz and Abdelhalem Mesfioui
Pathophysiology 2024, 31(4), 643-659; https://doi.org/10.3390/pathophysiology31040047 - 20 Nov 2024
Viewed by 2851
Abstract
Background/Objectives: Alzheimer’s disease (AD) remains incurable, highlighting the need for new and diverse animal models to better understand its complex mechanisms. This study compares various injected animal models of AD, focusing on the main theories that explain the disease; Methods: Female Wistar rats [...] Read more.
Background/Objectives: Alzheimer’s disease (AD) remains incurable, highlighting the need for new and diverse animal models to better understand its complex mechanisms. This study compares various injected animal models of AD, focusing on the main theories that explain the disease; Methods: Female Wistar rats (10-months old) were administered intracebroventricularly by artificial cerebrospinal fluid (aCSF) (Control), beta amyloid Aβ1-42 (BA), okadaic acid (OKA), lipopolysaccharides (LPS), buthionine sulfoximine (BSO) or by a mixture of these different molecules (MLG). Cognitive performance was assessed one week or one month after stereotaxic surgery; Results: Our results, show that only the Aβ and the MLG induced a persistence and progressive deficits in the working memory, recognition memory and spatial memory in rats. As the hippocampus (HIP) and the prefrontal cortex (PFC) are particularly involved in memory behavior, we analyzed long-term neuroadaptations in these brain subregions using spectrophotometric and histological methods to assess oxidative stress changes and neuronal loss, respectively. We found that the behavioral impairments in memory and learning were accompanied by irreversible oxidative stress changes and neurodegenerescence, particularly in the HIP; Conclusions: This study provides promising data on the modeling of AD in order to develop an effective therapeutic approach. Full article
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