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14 pages, 2501 KiB  
Article
Therapeutic Patterns and Surgical Decision-Making in Breast Cancer: A Retrospective Regional Cohort Study in Romania
by Ramona Andreea Cioroianu, Michael Schenker, Virginia-Maria Rădulescu, Tradian Ciprian Berisha, George Ovidiu Cioroianu, Mihaela Popescu, Cristina Mihaela Ciofiac, Ana Maria Petrescu and Stelian Ștefăniță Mogoantă
Clin. Pract. 2025, 15(8), 145; https://doi.org/10.3390/clinpract15080145 - 5 Aug 2025
Abstract
Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to [...] Read more.
Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to lung cancer. Methods: This study looked at 79 breast cancer patients from Oltenia, concentrating on epidemiology, histology, diagnostic features, and treatments. Patients were chosen based on inclusion criteria such as histopathologically verified diagnosis, availability of clinical and treatment data, and follow-up information. The analyzed biological material consisted of tissue samples taken from the breast parenchyma and axillary lymph nodes. Even though not the primary subject of this paper, all patients underwent immunohistochemical (IHC) evaluation both preoperatively and postoperatively. Results: We found invasive ductal carcinoma to be the predominant type, while ductal carcinoma in situ (DCIS) and mixed types were rare. We performed cross-tabulations of metastasis versus nodal status and age versus therapy type; none reached significance (all p > 0.05), suggesting observed differences were likely due to chance. A chi-square test comparing surgical interventions (breast-conserving vs. mastectomy) in patients who did or did not receive chemotherapy showed, χ2 = 3.17, p = 0.367, indicating that chemotherapy did not significantly influence surgical choice. Importantly, adjuvant chemotherapy and radiotherapy were used at similar rates across age groups, whereas neoadjuvant hormonal (endocrine) therapy was more common in older patients (but without statistical significance). Conclusions: Finally, we discussed the consequences of individualized care and early detection. Romania’s shockingly low screening rate, which contributes to delayed diagnosis, emphasizes the importance of improved population medical examination and tailored treatment options. Also, the country has one of the lowest rates of mammography uptake in Europe and no systematic population screening program. Full article
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16 pages, 4074 KiB  
Article
Exploring 6-aza-2-Thiothymine as a MALDI-MSI Matrix for Spatial Lipidomics of Formalin-Fixed Paraffin-Embedded Clinical Samples
by Natalia Shelly Porto, Simone Serrao, Greta Bindi, Nicole Monza, Claudia Fumagalli, Vanna Denti, Isabella Piga and Andrew Smith
Metabolites 2025, 15(8), 531; https://doi.org/10.3390/metabo15080531 - 5 Aug 2025
Abstract
Background/Objectives: In recent years, lipids have emerged as critical regulators of different disease processes, being involved in cancer pathogenesis, progression, and outcome. Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) has significantly expanded the technology’s reach, enabling spatially resolved profiling of lipids directly [...] Read more.
Background/Objectives: In recent years, lipids have emerged as critical regulators of different disease processes, being involved in cancer pathogenesis, progression, and outcome. Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) has significantly expanded the technology’s reach, enabling spatially resolved profiling of lipids directly from tissue, including formalin-fixed paraffin-embedded (FFPE) specimens. In this context, MALDI matrix selection is crucial for lipid extraction and ionization, influencing key aspects such as molecular coverage and sensitivity, especially in such specimens with already depleted lipid content. Thus, in this work, we aim to explore the feasibility of mapping lipid species in FFPE clinical samples with MALDI-MSI using 6-aza-2-thiothymine (ATT) as a matrix of choice. Methods: To do so, ATT performances were first compared to those two other matrices commonly used for lipidomic analyses, 2′,5′-dihydroxybenzoic acid (DHB) and Norharmane (NOR), on lipid standards. Results: As a proof-of-concept, we then assessed ATT’s performance for the MALDI-MSI analysis of lipids in FFPE brain sections, both in positive and negative ion modes, comparing results with those obtained from other commonly used dual-polarity matrices. In this context, ATT enabled the putative annotation of 98 lipids while maintaining a well-balanced detection of glycerophospholipids (60.2%) and sphingolipids (32.7%) in positive ion mode. It outperformed both DHB and NOR in the identification of glycolipids (3%) and fatty acids (4%). Additionally, ATT exceeded DHB in terms of total lipid count (62 vs. 21) and class diversity and demonstrated performance comparable to NOR in negative ion mode. Moreover, ATT was applied to a FFPE glioblastoma tissue microarray (TMA) evaluating the ability of this matrix to reveal biologically relevant lipid features capable of distinguishing normal brain tissue from glioblastoma regions. Conclusions: Altogether, the results presented in this work suggest that ATT is a suitable matrix for pathology imaging applications, even at higher lateral resolutions of 20 μm, not only for proteomic but also for lipidomic analysis. This could enable the use of the same matrix type for the analysis of both lipids and peptides on the same tissue section, offering a unique strategic advantage for multi-omics studies, while also supporting acquisition in both positive and negative ionization modes. Full article
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17 pages, 17592 KiB  
Article
Functional Identification of Acetyl-CoA C-Acetyltransferase Gene from Fritillaria unibracteata
by Zichun Ma, Qiuju An, Xue Huang, Hongting Liu, Feiying Guo, Han Yan, Jiayu Zhou and Hai Liao
Horticulturae 2025, 11(8), 913; https://doi.org/10.3390/horticulturae11080913 (registering DOI) - 4 Aug 2025
Abstract
Fritillaria unibracteata is a rare and endangered medicinal plant in the Liliaceae family, whose bulbs have been used in traditional Chinese traditional medicine for over 2000 years. The mevalonate (MVA) pathway is involved in the growth, development, response to environmental stress, and active [...] Read more.
Fritillaria unibracteata is a rare and endangered medicinal plant in the Liliaceae family, whose bulbs have been used in traditional Chinese traditional medicine for over 2000 years. The mevalonate (MVA) pathway is involved in the growth, development, response to environmental stress, and active ingredient production of plants; however, the functional characterization of MVA-pathway genes in the Liliaceae family remains poorly documented. In this study, an Acetyl-CoA C-acetyltransferase gene (FuAACT) was first cloned from F. unibracteata. It exhibited structural features of the thiolase family and showed the highest sequence identity with the Dioscorea cayenensis homolog. The Km, Vmax, and Kcat of the recombinant FuAACT were determined to be 3.035 ± 0.215 μM, 0.128 ± 0.0058 μmol/(min·mg), and 1.275 ± 0.0575 min−1, respectively. The optimal catalytic conditions for FuAACT were ascertained to be 30 °C and pH 8.9. It was stable below 50 °C. His361 was confirmed to be a key amino acid residue to enzymatic catalysis by site-directed mutagenesis. Subsequent subcellular localization experiments demonstrated that FuAACT was localized in chloroplasts and cytoplasm. FuAACT-overexpressing transgenic Arabidopsis thaliana plants showed higher drought tolerance than wild-type plants. This phenotypic difference was corroborated by significant differences in seed germination rate, lateral root number, plant height, and leaf number (p < 0.05). Furthermore, the FuAACT transgenic plants resulted in the formation of a more developed fibrous root system. These results indicated that the FuAACT gene revealed substantial biological activity in vitro and in vivo, hopefully providing the basis for its further research and application in liliaceous ornamental and medicinal plants. Full article
(This article belongs to the Special Issue Tolerance of Horticultural Plants to Abiotic Stresses)
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18 pages, 2852 KiB  
Article
Fe3O4@β-cyclodextrin Nanosystem: A Promising Adjuvant Approach in Cancer Treatment
by Claudia Geanina Watz, Ciprian-Valentin Mihali, Camelia Oprean, Lavinia Krauss Maldea, Calin Adrian Tatu, Mirela Nicolov, Ioan-Ovidiu Sîrbu, Cristina A. Dehelean, Vlad Socoliuc and Elena-Alina Moacă
Nanomaterials 2025, 15(15), 1192; https://doi.org/10.3390/nano15151192 - 4 Aug 2025
Abstract
The high incidence of melanoma leading to a poor prognosis rate endorses the development of alternative and innovative approaches in the treatment of melanoma. Therefore, the present study aims to develop and characterize, in terms of physicochemical features and biological impact, an aqueous [...] Read more.
The high incidence of melanoma leading to a poor prognosis rate endorses the development of alternative and innovative approaches in the treatment of melanoma. Therefore, the present study aims to develop and characterize, in terms of physicochemical features and biological impact, an aqueous suspension of magnetite (Fe3O4) coated with β-cyclodextrin (Fe3O4@β-CD) as a potential innovative alternative nanosystem for melanoma therapy. The nanosystem exhibited physicochemical characteristics suitable for biological applications, revealing a successful complexation of Fe3O4 NPs with β-CD and an average size of 18.1 ± 2.1 nm. In addition, the in vitro evaluations revealed that the newly developed nanosystem presented high biocompatibility on a human keratinocyte (HaCaT) monolayer and selective antiproliferative activity on amelanotic human melanoma (A375) cells, inducing early apoptosis features when concentrations of 10, 15, and 20 μg/mL were employed for 48 h and 72 h. Collectively, the Fe3O4@β-CD nanosystem reveals promising features for an adjuvant approach in melanoma treatment, mainly due to its β-cyclodextrin coating, thus endorsing a potential co-loading of therapeutic drugs. Furthermore, the intrinsic magnetic core of Fe3O4 NPs supports the magnetically based cancer treatment strategies. Full article
(This article belongs to the Special Issue Synthesis of Functional Nanoparticles for Biomedical Applications)
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28 pages, 1877 KiB  
Review
Unconventional Immunotherapies in Cancer: Opportunities and Challenges
by Meshael Alturki, Abdullah A. Alshehri, Ahmad M. Aldossary, Mohannad M. Fallatah, Fahad A. Almughem, Nojoud Al Fayez, Majed A. Majrashi, Ibrahim A. Alradwan, Mohammad Alkhrayef, Mohammad N. Alomary and Essam A. Tawfik
Pharmaceuticals 2025, 18(8), 1154; https://doi.org/10.3390/ph18081154 - 4 Aug 2025
Abstract
Conventional immunotherapy, including immune checkpoint blockade and chimeric antigen receptor (CAR)-T cells, has revolutionized cancer therapy over the past decade. Yet, the efficacy of these therapies is limited by tumor resistance, antigen escape mechanisms, poor persistence, and T-cell exhaustion, particularly in the treatment [...] Read more.
Conventional immunotherapy, including immune checkpoint blockade and chimeric antigen receptor (CAR)-T cells, has revolutionized cancer therapy over the past decade. Yet, the efficacy of these therapies is limited by tumor resistance, antigen escape mechanisms, poor persistence, and T-cell exhaustion, particularly in the treatment of solid tumors. The emergence of unconventional immunotherapies offers novel opportunities by leveraging diverse immune cell subsets and synthetic biologics. This review explores various immunotherapy platforms, including gamma delta T cells, invariant natural killer T cells, mucosal-associated invariant T cells, engineered regulatory T cells, and universal CAR platforms. Additionally, it expands on biologics, including bispecific and multispecific antibodies, cytokine fusions, agonists, and oncolytic viruses, showcasing their potential for modular engineering and off-the-shelf applicability. Distinct features of unconventional platforms include independence from the major histocompatibility complex (MHC), tissue-homing capabilities, stress ligand sensing, and the ability to bridge adaptive and innate immunity. Their compatibility with engineering approaches highlights their potential as scalable, efficient, and cost-effective therapies. To overcome translational challenges such as functional heterogeneity, immune exhaustion, tumor microenvironment-mediated suppression, and limited persistence, novel strategies will be discussed, including metabolic and epigenetic reprogramming, immune cloaking, gene editing, and the utilization of artificial intelligence for patient stratification. Ultimately, unconventional immunotherapies extend the therapeutic horizon of cancer immunotherapy by breaking barriers in solid tumor treatment and increasing accessibility. Continued investments in research for mechanistic insights and scalable manufacturing are key to unlocking their full clinical potential. Full article
(This article belongs to the Section Biopharmaceuticals)
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20 pages, 23283 KiB  
Article
Titanium–Aluminum–Vanadium Surfaces Generated Using Sequential Nanosecond and Femtosecond Laser Etching Provide Osteogenic Nanotopography on Additively Manufactured Implants
by Jonathan T. Dillon, David J. Cohen, Scott McLean, Haibo Fan, Barbara D. Boyan and Zvi Schwartz
Biomimetics 2025, 10(8), 507; https://doi.org/10.3390/biomimetics10080507 - 4 Aug 2025
Abstract
Titanium–aluminum–vanadium (Ti6Al4V) is a material chosen for spine, orthopedic, and dental implants due to its combination of desirable mechanical and biological properties. Lasers have been used to modify metal surfaces, enabling the generation of a surface on Ti6Al4V with distinct micro- and nano-scale [...] Read more.
Titanium–aluminum–vanadium (Ti6Al4V) is a material chosen for spine, orthopedic, and dental implants due to its combination of desirable mechanical and biological properties. Lasers have been used to modify metal surfaces, enabling the generation of a surface on Ti6Al4V with distinct micro- and nano-scale structures. Studies indicate that topography with micro/nano features of osteoclast resorption pits causes bone marrow stromal cells (MSCs) and osteoprogenitor cells to favor differentiation into an osteoblastic phenotype. This study examined whether the biological response of human MSCs to Ti6Al4V surfaces is sensitive to laser treatment-controlled micro/nano-topography. First, 15 mm diameter Ti6Al4V discs (Spine Wave Inc., Shelton, CT, USA) were either machined (M) or additively manufactured (AM). Surface treatments included no laser treatment (NT), nanosecond laser (Ns), femtosecond laser (Fs), or nanosecond followed by femtosecond laser (Ns+Fs). Surface wettability, roughness, and surface chemistry were determined using sessile drop contact angle, laser confocal microscopy, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). Human MSCs were cultured in growth media on tissue culture polystyrene (TCPS) or test surfaces. On day 7, the levels of osteocalcin (OCN), osteopontin (OPN), osteoprotegerin (OPG), and vascular endothelial growth factor 165 (VEGF) in the conditioned media were measured. M NT, Fs, and Ns+Fs surfaces were hydrophilic; Ns was hydrophobic. AM NT and Fs surfaces were hydrophilic; AM Ns and Ns+Fs were hydrophobic. Roughness (Sa and Sz) increased after Ns and Ns+Fs treatment for both M and AM disks. All surfaces primarily consisted of oxygen, titanium, and carbon; Fs had increased levels of aluminum for both M and AM. SEM images showed that M NT discs had a smooth surface, whereas AM surfaces appeared rough at a higher magnification. Fs surfaces had a similar morphology to their respective NT disc at low magnification, but higher magnification revealed nano-scale bumps not seen on NT surfaces. AM Fs surfaces also had regular interval ridges that were not seen on non-femto laser-ablated surfaces. Surface roughness was increased on M and AM Ns and Ns+Fs disks compared to NT and Fs disks. OCN was enhanced, and DNA was reduced on Ns and Ns+Fs, with no difference between them. OPN, OPG, and VEGF levels for laser-treated M surfaces were unchanged compared to NT, apart from an increase in OPG on Fs. MSCs grown on AM Ns and Ns+Fs surfaces had increased levels of OCN per DNA. These results indicate that MSCs cultured on AM Ns and AM Ns+Fs surfaces, which exhibited unique roughness at the microscale and nanoscale, had enhanced differentiation to an osteoblastic phenotype. The laser treatments of the surface mediated this enhancement of MSC differentiation and warrant further clinical investigation. Full article
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17 pages, 1702 KiB  
Article
Mobile and Wireless Autofluorescence Detection Systems and Their Application for Skin Tissues
by Yizhen Wang, Yuyang Zhang, Yunfei Li and Fuhong Cai
Biosensors 2025, 15(8), 501; https://doi.org/10.3390/bios15080501 - 3 Aug 2025
Viewed by 46
Abstract
Skin autofluorescence (SAF) detection technology represents a noninvasive, convenient, and cost-effective optical detection approach. It can be employed for the differentiation of various diseases, including metabolic diseases and dermatitis, as well as for monitoring the treatment efficacy. Distinct from diffuse reflection signals, the [...] Read more.
Skin autofluorescence (SAF) detection technology represents a noninvasive, convenient, and cost-effective optical detection approach. It can be employed for the differentiation of various diseases, including metabolic diseases and dermatitis, as well as for monitoring the treatment efficacy. Distinct from diffuse reflection signals, the autofluorescence signals of biological tissues are relatively weak, making them challenging to be captured by photoelectric sensors. Moreover, the absorption and scattering properties of biological tissues lead to a substantial attenuation of the autofluorescence of biological tissues, thereby worsening the signal-to-noise ratio. This has also imposed limitations on the development and application of compact-sized autofluorescence detection systems. In this study, a compact LED light source and a CMOS sensor were utilized as the excitation and detection devices for skin tissue autofluorescence, respectively, to construct a mobile and wireless skin tissue autofluorescence detection system. This system can achieve the detection of skin tissue autofluorescence with a high signal-to-noise ratio under the drive of a simple power supply and a single-chip microcontroller. The detection time is less than 0.1 s. To enhance the stability of the system, a pressure sensor was incorporated. This pressure sensor can monitor the pressure exerted by the skin on the detection system during the testing process, thereby improving the accuracy of the detection signal. The developed system features a compact structure, user-friendliness, and a favorable signal-to-noise ratio of the detection signal, holding significant application potential in future assessments of skin aging and the risk of diabetic complications. Full article
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14 pages, 2128 KiB  
Article
Correlation Measures in Metagenomic Data: The Blessing of Dimensionality
by Alessandro Fuschi, Alessandra Merlotti, Thi Dong Binh Tran, Hoan Nguyen, George M. Weinstock and Daniel Remondini
Appl. Sci. 2025, 15(15), 8602; https://doi.org/10.3390/app15158602 (registering DOI) - 2 Aug 2025
Viewed by 137
Abstract
Microbiome analysis has revolutionized our understanding of various biological processes, spanning human health and epidemiology (including antimicrobial resistance and horizontal gene transfer), as well as environmental and agricultural studies. At the heart of microbiome analysis lies the characterization of microbial communities through the [...] Read more.
Microbiome analysis has revolutionized our understanding of various biological processes, spanning human health and epidemiology (including antimicrobial resistance and horizontal gene transfer), as well as environmental and agricultural studies. At the heart of microbiome analysis lies the characterization of microbial communities through the quantification of microbial taxa and their dynamics. In the study of bacterial abundances, it is becoming more relevant to consider their relationship, to embed these data in the framework of network theory, allowing characterization of features like node relevance, pathways, and community structure. In this study, we address the primary biases encountered in reconstructing networks through correlation measures, particularly in light of the compositional nature of the data, within-sample diversity, and the presence of a high number of unobserved species. These factors can lead to inaccurate correlation estimates. To tackle these challenges, we employ simulated data to demonstrate how many of these issues can be mitigated by applying typical transformations designed for compositional data. These transformations enable the use of straightforward measures like Pearson’s correlation to correctly identify positive and negative relationships among relative abundances, especially in high-dimensional data, without having any need for further corrections. However, some challenges persist, such as addressing data sparsity, as neglecting this aspect can result in an underestimation of negative correlations. Full article
(This article belongs to the Special Issue Recent Advances in Biomedical Data Analysis)
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24 pages, 1396 KiB  
Article
Design of Experiments Leads to Scalable Analgesic Near-Infrared Fluorescent Coconut Nanoemulsions
by Amit Chandra Das, Gayathri Aparnasai Reddy, Shekh Md. Newaj, Smith Patel, Riddhi Vichare, Lu Liu and Jelena M. Janjic
Pharmaceutics 2025, 17(8), 1010; https://doi.org/10.3390/pharmaceutics17081010 - 1 Aug 2025
Viewed by 169
Abstract
Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription [...] Read more.
Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article
(This article belongs to the Special Issue Quality by Design in Pharmaceutical Manufacturing)
26 pages, 956 KiB  
Review
Natural Flavonoids for the Prevention of Sarcopenia: Therapeutic Potential and Mechanisms
by Ye Eun Yoon, Seong Hun Ju, Yebean Kim and Sung-Joon Lee
Int. J. Mol. Sci. 2025, 26(15), 7458; https://doi.org/10.3390/ijms26157458 - 1 Aug 2025
Viewed by 124
Abstract
Sarcopenia, characterized by progressive skeletal muscle loss and functional decline, represents a major public heath challenge in aging populations. Despite increasing awareness, current management strategies—primarily resistance exercise and nutritional support—remain limited by accessibility, adherence, and inconsistent outcomes. This underscores the urgent need for [...] Read more.
Sarcopenia, characterized by progressive skeletal muscle loss and functional decline, represents a major public heath challenge in aging populations. Despite increasing awareness, current management strategies—primarily resistance exercise and nutritional support—remain limited by accessibility, adherence, and inconsistent outcomes. This underscores the urgent need for novel, effective, and scalable therapeutics. Flavonoids, a diverse class of plant-derived polyphenolic compounds, have attracted attention for their muti-targeted biological activities, including anti-inflammatory, antioxidant, metabolic, and myogenic effects. This review aims to evaluate the anti-sarcopenic potential of selected flavonoids—quercetin, rutin, kaempferol glycosides, baicalin, genkwanin, isoschaftoside, naringin, eriocitrin, and puerarin—based on recent preclinical findings and mechanistic insights. These compounds modulate key pathways involved in muscle homeostasis, such as NF-κB and Nrf2 signaling, AMPK and PI3K/Akt activation, mitochondrial biogenesis, proteosomal degradation, and satellite cell function. Importantly, since muscle wasting also features prominently in cancer cachexia—a distinct but overlapping syndrome—understanding flavonoid action may offer broader therapeutic relevance. By targeting shared molecular axes, flavonoids may provide a promising, biologically grounded approach to mitigating sarcopenia and the related muscle-wasting conditions. Further translational studies and clinical trials are warranted to assess their efficacy and safety in human populations. Full article
(This article belongs to the Special Issue Role of Natural Products in Human Health and Disease)
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30 pages, 955 KiB  
Review
Breaking Barriers with Sound: The Implementation of Histotripsy in Cancer
by Ashutosh P. Raman, Parker L. Kotlarz, Alexis E. Giff, Katherine A. Goundry, Paul Laeseke, Erica M. Knavel Koepsel, Mosa Alhamami and Dania Daye
Cancers 2025, 17(15), 2548; https://doi.org/10.3390/cancers17152548 - 1 Aug 2025
Viewed by 295
Abstract
Histotripsy is a novel, noninvasive, non-thermal technology invented in 2004 for the precise destruction of biologic tissue. It offers a powerful alternative to more conventional thermal or surgical interventions. Using short-pulse, low-duty cycle ultrasonic waves, histotripsy creates cavitation bubble clouds that selectively and [...] Read more.
Histotripsy is a novel, noninvasive, non-thermal technology invented in 2004 for the precise destruction of biologic tissue. It offers a powerful alternative to more conventional thermal or surgical interventions. Using short-pulse, low-duty cycle ultrasonic waves, histotripsy creates cavitation bubble clouds that selectively and precisely destroy targeted tissue in a predefined volume while sparing critical structures like bile ducts, ureters, and blood vessels. Such precision is of value when treating tumors near vital structures. The FDA has cleared histotripsy for the treatment of all liver tumors. Major medical centers are currently spearheading clinical trials, and some institutions have already integrated the technology into patient care. Histotripsy is now being studied for a host of other cancers, including primary kidney and pancreatic tumors. Preclinical murine and porcine models have already revealed promising outcomes. One of histotripsy’s primary advantages is its non-thermal mechanical actuation. This feature allows it to circumvent the limitations of heat-based techniques, including the heat sink effect and unpredictable treatment margins near sensitive tissues. In addition to its non-invasive ablative capacities, it is being preliminarily explored for its potential to induce immunomodulation and promote abscopal inhibition of distant, untreated tumors through CD8+ T cell responses. Thus, it may provide a multilayered therapeutic effect in the treatment of cancer. Histotripsy has the potential to improve precision and outcomes across a multitude of specialties, from oncology to cardiovascular medicine. Continued trials are crucial to further expand its applications and validate its long-term efficacy. Due to the speed of recent developments, the goal of this review is to provide a comprehensive and updated overview of histotripsy. It will explore its physics-based mechanisms, differentiating it from similar technologies, discuss its clinical applications, and examine its advantages, limitations, and future. Full article
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17 pages, 4219 KiB  
Article
Identification of Differentially Expressed Genes and Pathways in Non-Diabetic CKD and Diabetic CKD by Integrated Human Transcriptomic Bioinformatics Analysis
by Clara Barrios, Marta Riera, Eva Rodríguez, Eva Márquez, Jimena del Risco, Melissa Pilco, Jorge Huesca, Ariadna González, Claudia Martyn, Jordi Pujol, Anna Buxeda and Marta Crespo
Int. J. Mol. Sci. 2025, 26(15), 7421; https://doi.org/10.3390/ijms26157421 - 1 Aug 2025
Viewed by 138
Abstract
Chronic kidney disease (CKD) is a heterogeneous condition with various etiologies, including type 2 diabetes mellitus (T2D), hypertension, and autoimmune disorders. Both diabetic CKD (CKD_T2D) and non-diabetic CKD (CKD_nonT2D) share overlapping clinical features, but understanding the molecular mechanisms underlying each subtype and distinguishing [...] Read more.
Chronic kidney disease (CKD) is a heterogeneous condition with various etiologies, including type 2 diabetes mellitus (T2D), hypertension, and autoimmune disorders. Both diabetic CKD (CKD_T2D) and non-diabetic CKD (CKD_nonT2D) share overlapping clinical features, but understanding the molecular mechanisms underlying each subtype and distinguishing diabetic from non-diabetic forms remain poorly defined. To identify differentially expressed genes (DEGs) and enriched biological pathways between CKD_T2D and CKD_nonT2D cohorts, including autoimmune (CKD_nonT2D_AI) and hypertensive (CKD_nonT2D_HT) subtypes, through integrative transcriptomic analysis. Publicly available gene expression datasets from human glomerular and tubulointerstitial kidney tissues were curated and analyzed from GEO and ArrayExpress. Differential expression analysis and Gene Set Enrichment Analysis (GSEA) were conducted to assess cohort-specific molecular signatures. A considerable overlap in DEGs was observed between CKD_T2D and CKD_nonT2D, with CKD_T2D exhibiting more extensive gene expression changes. Hypertensive-CKD shared greater transcriptomic similarity with CKD_T2D than autoimmune-CKD. Key DEGs involved in fibrosis, inflammation, and complement activation—including Tgfb1, Timp1, Cxcl6, and C1qa/B—were differentially regulated in diabetic samples, where GSEA revealed immune pathway enrichment in glomeruli and metabolic pathway enrichment in tubulointerstitium. The transcriptomic landscape of CKD_T2D reveals stronger immune and metabolic dysregulation compared to non-diabetic CKD. These findings suggest divergent pathological mechanisms and support the need for tailored therapeutic approaches. Full article
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19 pages, 1625 KiB  
Review
The Potential of Functional Hydrogels in Burns Treatment
by Nathalie S. Ringrose, Ricardo W. J. Balk, Susan Gibbs, Paul P. M. van Zuijlen and H. Ibrahim Korkmaz
Gels 2025, 11(8), 595; https://doi.org/10.3390/gels11080595 - 31 Jul 2025
Viewed by 126
Abstract
Burn injuries are complex and require effective wound management strategies. Traditional treatments, such as dermal templates, are limited by simplified extracellular matrix (ECM) composition (e.g., collagen-elastin or collagen-glycosaminoglycan), sheet-based formats, and frequent use of animal-derived materials. These limitations can reduce wound conformity, biocompatibility, [...] Read more.
Burn injuries are complex and require effective wound management strategies. Traditional treatments, such as dermal templates, are limited by simplified extracellular matrix (ECM) composition (e.g., collagen-elastin or collagen-glycosaminoglycan), sheet-based formats, and frequent use of animal-derived materials. These limitations can reduce wound conformity, biocompatibility, and integration with host tissue. Functional hydrogels are being explored as alternatives due to properties such as high water content, biodegradability, adhesiveness, antimicrobial activity, and support for angiogenesis. Unlike standard templates, hydrogels can adapt to irregular wound shapes as in burn wounds and reach deeper tissue layers, supporting moisture retention, cell migration, and controlled drug delivery. These features may improve the wound environment and support healing in burns of varying severity. This review outlines recent developments in functional hydrogel technologies and compares them to current clinical treatments for burn care. Emphasis is placed on the structural and biological features that influence performance, including material composition, bioactivity, and integration capacity. Through an exploration of key mechanisms of action and clinical applications, this review highlights the benefits and challenges associated with hydrogel technology, providing insights into its future role in burn care. Full article
(This article belongs to the Special Issue Hydrogel for Tissue Engineering and Biomedical Therapeutics)
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22 pages, 2809 KiB  
Article
Evaluation of Baby Leaf Products Using Hyperspectral Imaging Techniques
by Antonietta Eliana Barrasso, Claudio Perone and Roberto Romaniello
Appl. Sci. 2025, 15(15), 8532; https://doi.org/10.3390/app15158532 (registering DOI) - 31 Jul 2025
Viewed by 100
Abstract
The transition to efficient production requires innovative water control techniques to maximize irrigation efficiency and minimize waste. Analyzing and optimizing irrigation practices is essential to improve water use and reduce environmental impact. The aim of the research was to identify a discrimination method [...] Read more.
The transition to efficient production requires innovative water control techniques to maximize irrigation efficiency and minimize waste. Analyzing and optimizing irrigation practices is essential to improve water use and reduce environmental impact. The aim of the research was to identify a discrimination method to analyze the different hydration levels in baby-leaf products. The species being researched was spinach, harvested at the baby leaf stage. Utilizing a large dataset of 261 wavelengths from the hyperspectral imaging system, the feature selection minimum redundancy maximum relevance (FS-MRMR) algorithm was applied, leading to the development of a neural network-based prediction model. Finally, a mathematical classification model K-NN (k-nearest neighbors type) was developed in order to identify a transfer function capable of discriminating the hyperspectral data based on a threshold value of absolute leaf humidity. Five significant wavelengths were identified for estimating the moisture content of baby leaves. The resulting model demonstrated a high generalization capability and excellent correlation between predicted and measured data, further confirmed by the successful training, validation, and testing of a K-NN-based statistical classifier. The construction phase of the statistical classifier involved the use of the experimental dataset and the critical humidity threshold value of 0.83 (83% of leaf humidity) was considered, below which the baby-leaf crop requires the irrigation intervention. High percentages of correct classification were achieved for data within two humidity classes. Specifically, the statistical classifier demonstrated excellent performance, with 81.3% correct classification for samples below the threshold and 99.4% for those above it. The application of advanced spectral analysis and artificial intelligence methods has led to significant progress in leaf moisture analysis and prediction, yielding substantial implications for both agriculture and biological research. Full article
(This article belongs to the Special Issue Advances in Automation and Controls of Agri-Food Systems)
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14 pages, 886 KiB  
Article
An Innovative Approach for Maximum Recovery of Isoflavones from Glycine max by the Design of Experiments Method
by Aleksandra Bibow, Sławomir Dresler and Marta Oleszek
Appl. Sci. 2025, 15(15), 8442; https://doi.org/10.3390/app15158442 - 30 Jul 2025
Viewed by 236
Abstract
Isoflavones are the main phenolic compounds of soybean that affect its biological activity. The quantity of these valuable compounds extracted from plant material can significantly vary, influenced by the chosen extraction method and the specific extractants employed. Moreover, in cosmetics and pharmacy, the [...] Read more.
Isoflavones are the main phenolic compounds of soybean that affect its biological activity. The quantity of these valuable compounds extracted from plant material can significantly vary, influenced by the chosen extraction method and the specific extractants employed. Moreover, in cosmetics and pharmacy, the application of non-toxic, eco-friendly solvents is very important. This study aimed to develop the best mixture of extractants to maximize the recovery of individual isoflavones from soybean seeds by optimization of the proportion of three components: ethanol, water, and propanediol. The design of experiments (DOE) method was strategically employed. The extracts were obtained through accelerated solvent extraction and meticulously analyzed for isoflavone content using advanced electrospray ionization–time of flight–mass spectrometry (ESI-TOF-MS) profiling. The predominant isoflavones were daidzin, genistin, malonylgenistin, malonyldaidzin, and malonylglycitin. Our experiment demonstrated that employing three extractants in a balanced 1:1:1 v/v/v ratio resulted in the highest isolation of isoflavones compared to all other mixtures tested. Nevertheless, a detailed exploration of approximate values and utility profiles revealed a more effective composition for extraction efficiency. This optimal mixture features 32.8% ethanol, 39.2% water, and 27.8% propanediol, maximizing the yield of isoflavones from soybean seeds. The innovative use of mixture design and triangular response surfaces has proven to be a powerful approach for developing this superior three-component extraction mixture. This innovative approach not only enhances extraction efficiency but also paves the way for improved processing methods in the industry. Full article
(This article belongs to the Special Issue Advanced Phytochemistry and Its Applications)
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