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Marine noise pollution is a significant threat to global marine ecosystems and human activities. Most underwater sound-absorbing materials operate in the mid-to high-frequency bands (typically 1–10 kHz for mid-frequency and above 10 kHz for high-frequency), and current underwater low-frequency sound absorption performance remains unsatisfactory, with large structural sizes. To address these issues, a novel metasurface composed of a hexagonal Helmholtz resonator structure made of rubber and metal, combined with an embedded rough neck, is proposed. By introducing roughness into the neck of the Helmholtz resonator, this structure effectively provides the necessary acoustic impedance for low-frequency sound absorption without changing the overall size, thus lowering the resonance frequency. The finite element method is used for simulation, and theoretical validation is performed. The results show that the Helmholtz resonator with the rough neck achieves near-perfect acoustic absorption at a deep subwavelength scale at 81 Hz. At the absorption peak, the wavelength of the sound wave is 370 times the thickness of the resonator. By coupling seven absorption units and optimizing the parameters using a genetic algorithm, the metasurface achieves an average absorption coefficient greater than 0.9 in the 60 Hz to 260 Hz range. The complementary sound absorption coefficients of the unit cells at different frequency bands effectively broaden the absorption bandwidth. Full article

18 pages, 4777 KiB

Open AccessArticle

Battery-Free Innovation: An RF-Powered Implantable Microdevice for Intravesical Chemotherapy

by Obidah Alsayed Ali and Evren Degirmenci

Appl. Sci. 2025, 15(17), 9304; https://doi.org/10.3390/app15179304 (registering DOI) - 24 Aug 2025

Abstract

This study presents the development of an innovative battery-free, RF-powered implantable microdevice designed for intravesical chemotherapy delivery. The system utilizes a custom-designed RF energy harvesting module that enables wireless energy transfer through biological tissue, eliminating the need for internal power sources. Mechanical and electronic components were co-optimized to achieve full functionality within a compact, biocompatible housing suitable for intravesical implantation. The feasibility of the device was validated through simulation studies and ex vivo experiments using biological tissue models. The results demonstrated successful energy transmission, storage, and sequential actuator activation within a biological environment. The proposed system offers a promising platform for minimally invasive, wirelessly controlled drug delivery applications in oncology and other biomedical fields. Full article

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21 pages, 2000 KiB

Open AccessReview

Diabetic Kidney Disease: From Pathophysiology to Regression of Albuminuria and Kidney Damage: Is It Possible?

by Georgia Doumani, Panagiotis Theofilis, Aikaterini Vordoni, Vasileios Thymis, George Liapis, Despina Smirloglou and Rigas G. Kalaitzidis

Int. J. Mol. Sci. 2025, 26(17), 8224; https://doi.org/10.3390/ijms26178224 (registering DOI) - 24 Aug 2025

Abstract

Diabetes mellitus (DM) poses an increasingly high global health burden nowadays, while in adults, chronic kidney disease (CKD) associated with DM impacts 20–40% of those with the condition. Effective management of CKD in patients with diabetes necessitates a comprehensive, multidisciplinary approach. Numerous factors, including glomerular hyperfiltration, oxidative stress, inflammation, and hypoxia are linked to the advancement of diabetic kidney disease (DKD). Currently, no specific treatment for DKD has been established, prompting extensive exploration of new approaches. Renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter 2 inhibitors have demonstrated renoprotective effects in various human clinical trials. Additionally, glucagon-like peptide 1 receptor agonists and mineralocorticoid receptor antagonists have been reported as effective in managing DKD, while new therapeutic candidates are also under investigation, such as soluble guanylate cyclase activators and aldosterone synthase inhibitors. Recent evidence has shown that treating diabetic nephropathy by reducing albuminuria levels and retarding its progression is a complex skill. The purpose of this review is to support the impressive results that appear in reducing albuminuria and the progression of diabetic nephropathy with early and intensive combination treatment compared to the recently emerged conventional monotherapy, with agents that act on different pathophysiological mechanisms. Full article

(This article belongs to the Collection Latest Review Papers in Endocrinology and Metabolism)

19 pages, 4308 KiB

Open AccessArticle

Histology of Pompia Peel and Bioactivity of Its Essential Oil: A New Citrus-Based Approach to Skin Regeneration

by Emma Cocco, Giulia Giorgi, Valeria Marsigliesi, Francesco Mura, Jorge M. Alves-Silva, Mónica Zuzarte, Lígia Salgueiro, Valentina Ghiani, Enrico Sanjust, Danilo Falconieri, Delia Maccioni, Alessio Valletta, Elisa Brasili and Andrea Maxia

Pharmaceuticals 2025, 18(9), 1256; https://doi.org/10.3390/ph18091256 (registering DOI) - 24 Aug 2025

Abstract

Background/Objectives: Pompia is an ancient, endemic citrus ecotype native to Sardinia (Italy), characterized by distinctive morphology and high content of bioactive compounds. Despite increasing interest, several aspects of this fruit, including its histological characteristics, remain poorly understood. This study aims to address this gap by investigating the anatomical features and spatial distribution of secretory cavities involved in essential oil (EO) production and accumulation, while also evaluating the EO’s chemical profile and associated biological activity. Methods: Pompia peel (flavedo and albedo) was subjected to histological analysis through fixation, dehydration, resin inclusion and sectioning. Sections were stained with 0.05% toluidine blue and observed under a light microscope to measure different parameters of secretory cavities. Essential oil (EO) was obtained from Pompia peel by hydrodistillation and characterized by gas chromatography–mass spectrometry (GC–MS) analysis. The biological activity of Pompia EO was assessed in vitro using NIH/3T3 fibroblasts, where wound-healing was evaluated by scratch assay and anti-senescence effects by β-galactosidase and γH2AX activity. Results: Microscopic analysis of the peel revealed pronounced variability in depth and size of the secretory cavities, along with the presence of lenticel-like structures in the epidermis. GC–MS analysis showed that Pompia EO is dominated by limonene (89%), with minor compounds including myrcene, geranial and neral. In vitro biological assays demonstrated that the EO promotes cell migration in a wound-healing model at concentrations ≥ 12.5 µg/mL and reduces markers of cellular senescence, including β-galactosidase activity and γH2AX foci, in etoposide-induced senescent fibroblasts. Conclusions: Overall, this study provides the first histological characterization of Pompia peel and confirms the bioactive potential of its EO. These findings support future applications in skin regeneration and anti-aging strategies and contribute to the valorization of this underexplored Citrus ecotype. Full article

(This article belongs to the Special Issue Advances in the Chemical-Biological Knowledge of Essential Oils)

22 pages, 639 KiB

Open AccessReview

Postbiotics of Marine Origin and Their Therapeutic Application

by Isabel M. Cerezo, Olivia Pérez-Gómez, Sonia Rohra-Benítez, Marta Domínguez-Maqueda, Jorge García-Márquez and Salvador Arijo

Mar. Drugs 2025, 23(9), 335; https://doi.org/10.3390/md23090335 (registering DOI) - 24 Aug 2025

Abstract

The increase in antibiotic-resistant pathogens has prompted the search for alternative therapies. One such alternative is the use of probiotic microorganisms. However, growing interest is now turning toward postbiotics—non-viable microbial cells and/or their components or metabolites—that can confer health benefits without the risks associated with administering live microbes. Marine ecosystems, characterized by extreme and diverse environmental conditions, are a promising yet underexplored source of microorganisms capable of producing unique postbiotic compounds. These include bioactive peptides, polysaccharides, lipoteichoic acids, and short-chain fatty acids produced by marine bacteria. Such compounds often exhibit enhanced stability and potent biological activity, offering therapeutic potential across a wide range of applications. This review explores the current knowledge on postbiotics of marine origin, highlighting their antimicrobial, anti-inflammatory, immunomodulatory, and anticancer properties. We also examine recent in vitro and in vivo studies that demonstrate their efficacy in human and animal health. Some marine bacteria that have been studied for use as postbiotics belong to the genera Bacillus, Halobacillus, Halomonas, Mameliella, Shewanella, Streptomyces, Pseudoalteromonas, Ruegeria, Vibrio, and Weissella. In conclusion, although the use of the marine environment as a source of postbiotics is currently limited compared to other environments, studies conducted to date demonstrate its potential. Full article

(This article belongs to the Section Marine-Derived Ingredients for Drugs, Cosmeceuticals and Nutraceuticals)

25 pages, 1484 KiB

Open AccessReview

Expression of CD44 and Its Spliced Variants: Innate and Inducible Roles in Nervous Tissue Cells and Their Environment

by Maria Concetta Geloso, Francesco Ria, Valentina Corvino and Gabriele Di Sante

Int. J. Mol. Sci. 2025, 26(17), 8223; https://doi.org/10.3390/ijms26178223 (registering DOI) - 24 Aug 2025

Abstract

CD44, a structurally diverse cell-surface glycoprotein, plays a multifaceted and indispensable role in neural tissue across both physiological and pathological conditions. It orchestrates complex cell–extracellular matrix interactions and intracellular signaling through its variant isoforms and post-translational modifications and is broadly expressed in neural stem/progenitor cells, microglia, astrocytes, and selected neuronal populations. The interactions of CD44 with ligands such as hyaluronan and osteopontin regulate critical cellular functions, including migration, differentiation, inflammation, and synaptic plasticity. In microglia and macrophages, CD44 mediates immune signaling and phagocytic activity, and it is dynamically upregulated in neuroinflammatory diseases, particularly through pathways involving Toll-like receptor 4. CD44 expression in astrocytes is abundant during central nervous system development and in diseases, contributing to glial differentiation, reactive astrogliosis, and scar formation. Though its expression is less prominent in mature neurons, CD44 supports neural plasticity, circuit organization, and injury-induced repair mechanisms. Additionally, its expression at nervous system barriers, such as the blood–brain barrier, underscores its role in regulating vascular permeability during inflammation and ischemia. Collectively, CD44 emerges as a critical integrator of neural cell function and intercellular communication. Although the roles of CD44 in glial cells appear to be similar to those explored in other tissues, the expression of this molecule and its variants on neurons reveals peculiar functions. Elucidating the cell-type-specific roles and regulation of CD44 variants may offer novel therapeutic strategies for diverse neurological disorders. Full article

(This article belongs to the Collection Feature Papers in Molecular Neurobiology)

24 pages, 2852 KiB

Open AccessArticle

Uracil–DNA Glycosylase from Beta vulgaris: Properties and Response to Abiotic Stress

by Daria V. Petrova, Maria V. Zateeva, Lijun Zhang, Jiajia Zhang, Ying Zhao, Natalya V. Permyakova, Alla A. Zagorskaya, Vasily D. Zharkov, Anton V. Endutkin, Bing Yu, Chunquan Ma, Haiying Li, Dmitry O. Zharkov and Inga R. Grin

Int. J. Mol. Sci. 2025, 26(17), 8221; https://doi.org/10.3390/ijms26178221 (registering DOI) - 24 Aug 2025

Abstract

Uracil−DNA glycosylases (UNGs) are DNA repair enzymes responsible for the removal of uracil, a canonical RNA nucleobase, from DNA, where it appears through cytosine deamination or incorporation from the cellular dUTP pool. While human and Escherichia coli UNGs have been extensively investigated, much less is known about their plant counterparts, of which UNGs from Arabidopsis thaliana are the only studied examples. Here, we show that in sugar beet (Beta vulgaris L.), an important crop species, cold and salt stress induce the expression of the UNG gene (BvUNG) and modulate the level of the uracil-excising activity in the roots. Purified recombinant BvUNG efficiently removes uracil from DNA both in vitro and in an E. coli reporter strain but does not excise 5-hydroxyuracil, 5,6-dihydrouracil, or 5-hydroxymethyluracil. The activity is abolished by Ugi, a protein UNG inhibitor from PBS1 bacteriophage, and by a mutation of a conserved active site His residue. Structural modeling shows the presence of a disordered N-tail prone to undergo phase separation, followed by a long α helix oriented differently from its counterpart in human UNG. Overall, BvUNG is a functional uracil–DNA glycosylase that might participate in the response to abiotic stress. Full article

(This article belongs to the Collection State-of-the-Art Macromolecules in Russia)

32 pages, 2441 KiB

Open AccessReview

Tailoring Therapy: Hydrogels as Tunable Platforms for Regenerative Medicine and Cancer Intervention

by Camelia Munteanu, Eftimia Prifti, Adrian Surd and Sorin Marian Mârza

Gels 2025, 11(9), 679; https://doi.org/10.3390/gels11090679 (registering DOI) - 24 Aug 2025

Abstract

Hydrogels are water-rich polymeric networks mimicking the body’s extracellular matrix, making them highly biocompatible and ideal for precision medicine. Their “tunable” and “smart” properties enable the precise adjustment of mechanical, chemical, and physical characteristics, allowing responses to specific stimuli such as pH or temperature. These versatile materials offer significant advantages over traditional drug delivery by facilitating targeted, localized, and on-demand therapies. Applications range from diagnostics and wound healing to tissue engineering and, notably, cancer therapy, where they deliver anti-cancer agents directly to tumors, minimizing systemic toxicity. Hydrogels’ design involves careful material selection and crosslinking techniques, which dictate properties like swelling, degradation, and porosity—all crucial for their effectiveness. The development of self-healing, tough, and bio-functional hydrogels represents a significant step forward, promising advanced biomaterials that can actively sense, react to, and engage in complex biological processes for a tailored therapeutic approach. Beyond their mechanical resilience and adaptability, these hydrogels open avenues for next-generation therapies, such as dynamic wound dressings that adapt to healing stages, injectable scaffolds that remodel with growing tissue, or smart drug delivery systems that respond to real-time biochemical cues. Full article

(This article belongs to the Special Issue Advances in Hydrogels for Regenerative Medicine)

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23 pages, 2112 KiB

Open AccessArticle

3D Printing as a Multimodal STEM Learning Technology: A Survey Study in Second Chance Schools

by Despina Radiopoulou, Antreas Kantaros, Theodore Ganetsos and Paraskevi Zacharia

Multimodal Technol. Interact. 2025, 9(9), 87; https://doi.org/10.3390/mti9090087 (registering DOI) - 24 Aug 2025

Abstract

This study explores the integration of 3D printing technology by adult learners in Greek Second Chance Schools (SCS), institutions designed to address Early School Leaving and promote Lifelong Learning. Grounded in constructivist and experiential learning theories, the research examines adult learners’ attitudes toward 3D printing technology through a hands-on STEM activity in the context of teaching scientific literacy. The instructional activity was centered on a physics experiment illustrating Archimedes’ principle using a multimodal approach, combining 3D computer modeling for visualization and design with tangible manipulation of a printed object, thereby offering both digital and Hands-on learning experiences. Quantitative data was collected using a structured questionnaire to assess participants’ perception toward the 3D printing technology. Findings indicate a positive trend in adult learners’ responses, finding 3D printing accessible, interesting, and easy to use. While expressing hesitation about independently applying the technology in the future, overall responses suggest strong interest and openness to using emerging technologies within educational settings, even among marginalized adult populations. This work highlights the value of integrating emerging technologies into alternative education frameworks and offers a replicable model for inclusive STEM education and lays the groundwork for further research in adult learning environments using innovative, learner-centered approaches. Full article

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20 pages, 2494 KiB

Open AccessArticle

α-Cyclodextrin/Moringin Impacts Actin Cytoskeleton Dynamics with Potential Implications for Synaptic Organization: A Preliminary Transcriptomic Study in NSC-34 Motor Neurons

by Agnese Gugliandolo, Luigi Chiricosta, Gabriella Calì, Patrick Rollin, Daniele Perenzoni, Renato Iori, Emanuela Mazzon and Simone D’Angiolini

Int. J. Mol. Sci. 2025, 26(17), 8220; https://doi.org/10.3390/ijms26178220 (registering DOI) - 24 Aug 2025

Abstract

α-Cyclodextrin/Moringin (α-CD/MOR) is an isothiocyanate showing neuroprotective and antioxidant properties. In this work, we studied in differentiated NSC-34 motor neurons cell line the molecular pathways activated following a treatment of 96 h with α-CD/MOR at different doses, namely 0.5, 5 and 10 μM. Taking advantage of comparative transcriptomic analysis, we retrieved the differentially expressed genes (DEGs) and we mapped DEGs to synaptic genes using the SynGO database. Then, we focused on the biological pathways in which they are involved. We observed that the prolonged treatment with α-CD/MOR significantly modulated biological processes and cellular components associated with synaptic organization. Interestingly, the KEGG pathway “Regulation of actin cytoskeleton” was overrepresented, alongside pathways related to synapses and axon guidance. Specifically, SPIA analysis indicated that the “Regulation of actin cytoskeleton” pathway was found to be activated with the highest dose of α-CD/MOR. Moreover, α-CD/MOR also modulated transcription factors involved in synaptic plasticity, such as Creb1. These results could indicate that α-CD/MOR can influence synaptic functions and organization, being involved in synaptic plasticity through the modulation of actin dynamics. Full article

(This article belongs to the Special Issue New Research on the Biological Activities of Natural Components and Their Application)

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15 pages, 1676 KiB

Open AccessArticle

Mitigating Oxidative Stress and Anti-Angiogenic State in an In Vitro Model of Preeclampsia by HY-12, an Organofluorine Hydrazone Antioxidant

by Zsuzsanna K. Zsengellér, Maxim Mastyugin, Adrianna R. Fusco, Bernadett Vlocskó, Maximilian Costa, Coryn Ferguson, Diana Pintye, Réka Eszter Sziva, Saira Salahuddin, Brett C. Young, Marianna Török and Béla Török

Curr. Issues Mol. Biol. 2025, 47(9), 680; https://doi.org/10.3390/cimb47090680 (registering DOI) - 24 Aug 2025

Abstract

Preeclampsia (PE) is a hypertensive disorder impacting 5–7% of pregnancies globally. With no causative treatment available, diagnosed patients have limited therapeutic options, putting them at risk for pregnancy complications. The induction of oxidative stress by ROS—one of the major contributors in PE pathogenesis—causes downstream signaling and production of anti-angiogenic factors, such as sFLT1 and sEng. The anti-angiogenic factors may cause endothelial and trophoblast dysfunction, contributing to the development of hypertension, proteinuria, and in severe cases, eclampsia. To target placental oxidative stress, we developed and evaluated an organofluorine hydrazone antioxidant, HY-12, in vitro. Human trophoblast (HTR8/SVneo) cells were incubated with hydrogen peroxide to induce oxidative stress and act as a model of PE. The goal of the study was to assess the efficacy of HY-12 and its ability to reduce cell injury, mitochondrial stress, and anti-angiogenic response. In our human trophoblast-based assays, pre-treatment with HY-12 reduced mitochondrial-derived ROS production in cells exposed to hydrogen peroxide, proving its ability to alleviate the oxidative stress associated with the pathogenesis of PE. HY-12 reduced HIF1A expression and sFLT1 protein expression in H₂O₂-exposed HTR8 cells. Furthermore, HY-12 improved the activity of the mitochondrial electron chain enzyme cytochrome C oxidase (COX) in the hydrogen-peroxide-treated HTR8/SVneo cells, which is a promising attribute of the compound. In reducing placental trophoblast oxidative stress, HY-12 shows promise as a potential treatment of preeclampsia. In vivo studies are warranted to further determine the efficacy of this compound. Full article

(This article belongs to the Special Issue Advanced Molecular Research on Hypertensive Disorders of Pregnancy (HDPs))

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14 pages, 2228 KiB

Open AccessArticle

Silver Nanoparticles@Zeolite Composites: Preparation, Characterization and Antibacterial Properties

by Gospodinka Gicheva, Marinela Panayotova, Orlin Gemishev, Sergei A. Kulinich and Neli Mintcheva

Materials 2025, 18(17), 3964; https://doi.org/10.3390/ma18173964 (registering DOI) - 24 Aug 2025

Abstract

The presence of various Ag species (Ag⁺ ions, Ag clusters, and Ag nanoparticles (NPs)) in Ag-zeolite nanocomposites strongly influences their catalytic, photocatalytic, and antibacterial properties. To tailor materials for specific applications, it is essential to employ strategies that control the redox processes between Ag⁺ and Ag⁰ and facilitate the formation of active Ag-containing composites. In this study, we present a comparative analysis of Ag-zeolite nanocomposites, focusing on their synthesis methods, structural characteristics, and antibacterial activity against Escherichia coli. Ag NPs were synthesized using three approaches: solid-state thermal reduction, chemical reduction in aqueous solutions with a mild reducing agent (sodium citrate, Na₃Cit), and chemical reduction with a strong reducing agent (sodium borohydride, NaBH₄). The resulting materials were characterized by X-ray diffraction (XRD), diffuse reflectance UV–Vis spectroscopy (DR UV–Vis), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM), while antibacterial activity was assessed using biological assays. Microscopic and spectroscopic analyses confirmed the formation of Ag NPs and the co-existence of immobilized Ag⁺ ions within the zeolite framework. The specific influence of the treatment method of Ag⁺-zeolite on the presence of silver species in the nanocomposites and their role in antibacterial properties were evaluated. The highest antibacterial efficiency was observed in the nanocomposite produced by thermal treatment of Ag-exchanged zeolite. Thus, the crucial function of Ag⁺ ions in the mechanism of bacteria cell death was suggested. Full article

(This article belongs to the Special Issue Research on Zeolites and Zeolite-Like Materials: Synthesis, Structure, Properties and Application)

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21 pages, 1205 KiB

Open AccessArticle

Development and Fuzzy Logic-Based Optimization of Golden Milk Formulations Using RW-Dried Turmeric Powder: A Study on Shelf Life, Sensory Attributes, and Functional Properties

by Preetisagar Talukdar, Kamal Narayan Baruah, Pankaj Jyoti Barman, Shagufta Rizwana, Sonu Sharma and Ramagopal V. S. Uppaluri

Foods 2025, 14(17), 2948; https://doi.org/10.3390/foods14172948 (registering DOI) - 24 Aug 2025

Abstract

The storage characteristics of folic acid and NaFeEDTA fortified in a refractance window-dried turmeric powder base and its subsequent application to the formulation of nutritionally functionalized golden milk have not been addressed in previous studies. Golden milk is a staple food and ideal matrix for the fortification of important nutrients such as iron and folic acid. With this motivation, the present study assesses refractance window (RW)-dried turmeric powder fortified with folic acid and NaFeEDTA in terms of its moisture isotherm, permeability of packing material, and storage parameters to calculate its shelf life. Further, a sensory analysis was conducted based on the fuzzy logic method to obtain the best constitution of RW-dried turmeric powder in milk. For the best formulation of golden milk, the characteristics of the product under unrefrigerated and refrigerated conditions were evaluated in addition to the storage study. Additionally, moisture content (MC), total flavonoid content (TFC), total phenolic content (TPC), antioxidant activity (AA), curcumin content (CC), color indices, bulk densities, solubility, swelling power, and water binding capacities were studied with respect to time. The results demonstrated a healthy shelf life of 184, 187, and 183 days for RW-dried, folic acid-fortified, and NaFeEDTA-fortified RW-dried turmeric powder samples, respectively, in the zipper pouch system. The fuzzy scores ranked the sample with 1 g concentration of turmeric powder as the best, considering taste, aroma, mouthfeel, aftertaste, consistency, and overall acceptability. The TPC, TFC, AA, and CC values for RW-dried turmeric powder in milk were 876.21 mg GAE/100 mL, 784.61 mg quercetin/100 mL, 24.50% and 4.20% w/w, respectively. Marginal alterations were found for the RW-dried fortified and unfortified turmeric samples. This fortified golden milk has the potential for use as a health drink. Full article

(This article belongs to the Section Food Packaging and Preservation)

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41 pages, 639 KiB

Open AccessReview

Clinical Role of Pharmacists in the Care of Incarcerated People at Correctional Facilities: A Scoping Review

by Christian Eduardo Castro Silva, Beatriz Bernava Sarinho, Michelle Bonafé, Tácio de Mendonça Lima, Inajara Rotta, Samara Jamile Mendes, Patricia Melo Aguiar and Marília Berlofa Visacri

Pharmacy 2025, 13(5), 113; https://doi.org/10.3390/pharmacy13050113 (registering DOI) - 24 Aug 2025

Abstract

This study aimed to map the literature on the clinical role of pharmacists in the care of incarcerated people at correctional facilities and to identify gaps in this field. A scoping review was conducted on 30 July 2024, using the PubMed, Scopus, and LILACS databases. Gray literature was searched via Google Scholar, and references of included studies were manually reviewed. Primary studies of any design reporting pharmacists’ clinical services and/or activities for incarcerated individuals were eligible. Study selection and data extraction were performed independently by two reviewers, with a third resolving disagreements. The search yielded 894 records, from which 27 studies were included. Most studies were conducted in the United States (n = 16; 59%) and France (n = 7; 26%). Eleven (41%) focused exclusively on male populations, and one (4%) on female inmates. Most studies addressed pharmacists’ clinical roles in mental health conditions and substance use disorders (n = 9; 33%), infectious diseases (n = 5; 19%), and diabetes (n = 4; 15%). Clinical services and/or activities related to direct patient care were the most frequently reported (n = 18; 67%). Process measures were reported in 18 studies (67%), and clinical outcomes were the most common type of outcome (n = 13; 48%). This review highlights the pharmacist’s clinical role in treating mental health conditions and substance abuse, infectious diseases, and diabetes in incarcerated care. It underscores the need for further research in low- and middle-income countries, on women’s health, and on other prevalent conditions. Full article

(This article belongs to the Section Pharmacy Practice and Practice-Based Research)

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20 pages, 5044 KiB

Open AccessArticle

FGF21–MAPK1 Imbalance Disrupts Hepatic Lipid Metabolism in Dairy Cow Ketosis

by Jun-Jie Xu, Fan Yang, Zhi-Xi Chen, Zhi-Peng Wang, Zi-Xuan Wang, Zi-Han Deng, Chen-Jie Xu, Fang-Hui Chen, Wei Zhang, Yang Liu and Ya-Fei Cai

Life 2025, 15(9), 1339; https://doi.org/10.3390/life15091339 (registering DOI) - 24 Aug 2025

Abstract

Background: Aberrant hepatic lipid metabolism is a key predisposing factor for dairy cow ketosis, with genetic factors playing a pivotal role in disease pathogenesis. However, systematic screening and functional validation of candidate genes for bovine ketosis remain limited. In this study, we aimed to identify genetic markers associated with clinical ketosis and explore their potential functional mechanisms underlying disease susceptibility. Methods: We conducted simplified genome sequencing (SuperGBS), genome-wide association studies (GWAS), and Sanger sequencing on Chinese Holstein cows, both healthy and with ketosis. Results: We reported that mitogen-activated protein kinase 1 (MAPK1) was significantly associated with clinical ketosis. Further investigation revealed concurrent upregulation of MAPK1 protein and disrupted hepatic lipid homeostasis in hepatocytes from in vivo and in vitro models. Critically, siRNA-mediated knockdown of MAPK1 reversed lipid metabolism processes and reduced lipid accumulation in β-Hydroxybutyric acid (BHB)-exposed bovine hepatocytes, thereby establishing MAPK1 activation as a driver of lipotoxicity in dairy cow ketosis. Additionally, we identified that supplementation of fibroblast growth factor 21 (FGF21) fusion protein not only reduced MAPK1 expression but also normalized hepatic lipid metabolism in BHB-exposed bovine hepatocytes. Conclusions: FGF21–MAPK1 imbalance is a reason for hepatic lipid metabolic dysfunction, providing a potential intervention approach to mitigate dairy cows’ ketosis. Full article

(This article belongs to the Special Issue Health Management of Farm Animals: Physiological and Pathological Aspects)

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