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33 pages, 4098 KiB  
Systematic Review
Pharmacological Inhibition of the PI3K/AKT/mTOR Pathway in Rheumatoid Arthritis Synoviocytes: A Systematic Review and Meta-Analysis (Preclinical)
by Tatiana Bobkova, Artem Bobkov and Yang Li
Pharmaceuticals 2025, 18(8), 1152; https://doi.org/10.3390/ph18081152 - 2 Aug 2025
Viewed by 84
Abstract
Background/Objectives: Constitutive activation of the PI3K/AKT/mTOR signaling cascade underlies the aggressive phenotype of fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA); however, a quantitative synthesis of in vitro data on pathway inhibition remains lacking. This systematic review and meta-analysis aimed to (i) aggregate [...] Read more.
Background/Objectives: Constitutive activation of the PI3K/AKT/mTOR signaling cascade underlies the aggressive phenotype of fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA); however, a quantitative synthesis of in vitro data on pathway inhibition remains lacking. This systematic review and meta-analysis aimed to (i) aggregate standardized effects of pathway inhibitors on proliferation, apoptosis, migration/invasion, IL-6/IL-8 secretion, p-AKT, and LC3; (ii) assess heterogeneity and identify key moderators of variability, including stimulus type, cell source, and inhibitor class. Methods: PubMed, Europe PMC, and the Cochrane Library were searched up to 18 May 2025 (PROSPERO CRD420251058185). Twenty of 2684 screened records met eligibility. Two reviewers independently extracted data and assessed study quality with SciRAP. Standardized mean differences (Hedges g) were pooled using a Sidik–Jonkman random-effects model with Hartung–Knapp confidence intervals. Heterogeneity (τ2, I2), 95% prediction intervals, and meta-regression by cell type were calculated; robustness was tested with REML-HK, leave-one-out, and Baujat diagnostics. Results: PI3K/AKT/mTOR inhibition markedly reduced proliferation (to –5.1 SD), IL-6 (–11.1 SD), and IL-8 (–6.5 SD) while increasing apoptosis (+2.7 SD). Fourteen of seventeen outcome clusters showed large effects (|g| ≥ 0.8), with low–moderate heterogeneity (I2 ≤ 35% in 11 clusters). Prediction intervals crossed zero only in small k-groups; sensitivity analyses shifted pooled estimates by ≤0.05 SD. p-AKT and p-mTOR consistently reflected functional changes and emerged as reliable pharmacodynamic markers. Conclusions: Targeted blockade of PI3K/AKT/mTOR robustly suppresses the proliferative and inflammatory phenotype of RA-FLSs, reaffirming this axis as a therapeutic target. The stability of estimates across multiple analytic scenarios enhances confidence in these findings and highlights p-AKT and p-mTOR as translational response markers. The present synthesis provides a quantitative basis for personalized dual-PI3K/mTOR strategies and supports the adoption of standardized long-term preclinical protocols. Full article
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16 pages, 340 KiB  
Review
Methodological Standards for Conducting High-Quality Systematic Reviews
by Alessandro De Cassai, Burhan Dost, Serkan Tulgar and Annalisa Boscolo
Biology 2025, 14(8), 973; https://doi.org/10.3390/biology14080973 (registering DOI) - 1 Aug 2025
Viewed by 184
Abstract
Systematic reviews are a cornerstone of evidence-based research, providing comprehensive summaries of existing studies to answer specific research questions. This article offers a detailed guide to conducting high-quality systematic reviews in biology, health and social sciences. It outlines key steps, including developing and [...] Read more.
Systematic reviews are a cornerstone of evidence-based research, providing comprehensive summaries of existing studies to answer specific research questions. This article offers a detailed guide to conducting high-quality systematic reviews in biology, health and social sciences. It outlines key steps, including developing and registering a protocol, designing comprehensive search strategies, and selecting studies through a screening process. The article emphasizes the importance of accurate data extraction and the use of validated tools to assess the risk of bias across different study designs. Both meta-analysis (quantitative approach) and narrative synthesis (qualitative approach) are discussed in detail. The guide also highlights the use of frameworks, such as GRADE, to assess the certainty of evidence and provides recommendations for clear and transparent reporting in line with the PRISMA 2020 guidelines. This paper aims to adapt and translate evidence-based review principles, commonly applied in clinical research, into the context of biological sciences. By highlighting domain-specific methodologies, challenges, and resources, we provide tailored guidance for researchers in ecology, molecular biology, evolutionary biology, and related fields in order to conduct transparent and reproducible evidence syntheses. Full article
(This article belongs to the Section Theoretical Biology and Biomathematics)
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11 pages, 1219 KiB  
Article
The Church and Academia Model: New Paradigm for Spirituality and Mental Health Research
by Marta Illueca, Samantha M. Meints, Megan M. Miller, Dikachi Osaji and Benjamin R. Doolittle
Religions 2025, 16(8), 998; https://doi.org/10.3390/rel16080998 (registering DOI) - 31 Jul 2025
Viewed by 142
Abstract
Ongoing interest in the intersection of spirituality and health has prompted a need for integrated research. This report proposes a distinct approach in a model that allows for successful and harmonious cross-fertilization within these latter two areas of interest. Our work is especially [...] Read more.
Ongoing interest in the intersection of spirituality and health has prompted a need for integrated research. This report proposes a distinct approach in a model that allows for successful and harmonious cross-fertilization within these latter two areas of interest. Our work is especially pertinent to inquiries around the role of spirituality in mental health, with special attention to chronic pain conditions. The latter have become an open channel for novel avenues to explore the field of spirituality-based interventions within the arena of psychological inquiry. To address this, the authors developed and implemented the Church and Academia Model, a prototype for an innovative collaborative research project, with the aim of exploring the role of devotional practices, and their potential to be used as therapeutic co-adjuvants or tools to enhance the coping skills of patients with chronic pain. Keeping in mind that the church presents a rich landscape for clinical inquiry with broad relevance for clinicians and society at large, we created a unique hybrid research model. This is a new paradigm that focuses on distinct and well-defined studies where the funding, protocol writing, study design, and implementation are shared by experts from both the pastoral and clinical spaces. A team of theologians, researchers, and healthcare providers, including clinical pain psychologists, built a coalition leveraging their respective skill sets. Each expert is housed in their own environs, creating a functional network that has proven academically productive and pastorally effective. Key outputs include the creation and validation of a new psychometric measure, the Pain-related PRAYER Scale (PPRAYERS), an associated bedside prayer tool and a full-scale dissemination strategy through journal publications and specialty society conferences. This collaborative prototype is also an ideal fit for integrated knowledge translation platforms, and it is a promising paradigm for future collaborative projects focused on spirituality and mental health. Full article
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31 pages, 3754 KiB  
Review
Artificial Gametogenesis and In Vitro Spermatogenesis: Emerging Strategies for the Treatment of Male Infertility
by Aris Kaltsas, Maria-Anna Kyrgiafini, Eleftheria Markou, Andreas Koumenis, Zissis Mamuris, Fotios Dimitriadis, Athanasios Zachariou, Michael Chrisofos and Nikolaos Sofikitis
Int. J. Mol. Sci. 2025, 26(15), 7383; https://doi.org/10.3390/ijms26157383 - 30 Jul 2025
Viewed by 355
Abstract
Male-factor infertility accounts for approxiamately half of all infertility cases globally, yet therapeutic options remain limited for individuals with no retrievable spermatozoa, such as those with non-obstructive azoospermia (NOA). In recent years, artificial gametogenesis has emerged as a promising avenue for fertility restoration, [...] Read more.
Male-factor infertility accounts for approxiamately half of all infertility cases globally, yet therapeutic options remain limited for individuals with no retrievable spermatozoa, such as those with non-obstructive azoospermia (NOA). In recent years, artificial gametogenesis has emerged as a promising avenue for fertility restoration, driven by advances in two complementary strategies: organotypic in vitro spermatogenesis (IVS), which aims to complete spermatogenesis ex vivo using native testicular tissue, and in vitro gametogenesis (IVG), which seeks to generate male gametes de novo from pluripotent or reprogrammed somatic stem cells. To evaluate the current landscape and future potential of these approaches, a narrative, semi-systematic literature search was conducted in PubMed and Scopus for the period January 2010 to February 2025. Additionally, landmark studies published prior to 2010 that contributed foundational knowledge in spermatogenesis and testicular tissue modeling were reviewed to provide historical context. This narrative review synthesizes multidisciplinary evidence from cell biology, tissue engineering, and translational medicine to benchmark IVS and IVG technologies against species-specific developmental milestones, ranging from rodent models to non-human primates and emerging human systems. Key challenges—such as the reconstitution of the blood–testis barrier, stage-specific endocrine signaling, and epigenetic reprogramming—are discussed alongside critical performance metrics of various platforms, including air–liquid interface slice cultures, three-dimensional organoids, microfluidic “testis-on-chip” devices, and stem cell-derived gametogenic protocols. Particular attention is given to clinical applicability in contexts such as NOA, oncofertility preservation in prepubertal patients, genetic syndromes, and reprocutive scenarios involving same-sex or unpartnered individuals. Safety, regulatory, and ethical considerations are critically appraised, and a translational framework is outlined that emphasizes biomimetic scaffold design, multi-omics-guided media optimization, and rigorous genomic and epigenomic quality control. While the generation of functionally mature sperm in vitro remains unachieved, converging progress in animal models and early human systems suggests that clinically revelant IVS and IVG applications are approaching feasibility, offering a paradigm shift in reproductive medicine. Full article
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23 pages, 3019 KiB  
Review
Phase-Transfer Catalysis for Fuel Desulfurization
by Xun Zhang and Rui Wang
Catalysts 2025, 15(8), 724; https://doi.org/10.3390/catal15080724 - 30 Jul 2025
Viewed by 205
Abstract
This review surveys recent advances and emerging prospects in phase-transfer catalysis (PTC) for fuel desulfurization. In response to increasingly stringent environmental regulations, the removal of sulfur from transportation fuels has become imperative for curbing SOx emissions. Conventional hydrodesulfurization (HDS) operates under severe [...] Read more.
This review surveys recent advances and emerging prospects in phase-transfer catalysis (PTC) for fuel desulfurization. In response to increasingly stringent environmental regulations, the removal of sulfur from transportation fuels has become imperative for curbing SOx emissions. Conventional hydrodesulfurization (HDS) operates under severe temperature–pressure conditions and displays limited efficacy toward sterically hindered thiophenic compounds, motivating the exploration of non-hydrogen routes such as oxidative desulfurization (ODS). Within ODS, PTC offers distinctive benefits by shuttling reactants across immiscible phases, thereby enhancing reaction rates and selectivity. In particular, PTC enables efficient migration of organosulfur substrates from the hydrocarbon matrix into an aqueous phase where they are oxidized and subsequently extracted. The review first summarizes the deployment of classic PTC systems—quaternary ammonium salts, crown ethers, and related agents—in ODS operations and then delineates the underlying phase-transfer mechanisms, encompassing reaction-controlled, thermally triggered, photo-responsive, and pH-sensitive cycles. Attention is next directed to a new generation of catalysts, including quaternary-ammonium polyoxometalates, imidazolium-substituted polyoxometalates, and ionic-liquid-based hybrids. Their tailored architectures, catalytic performance, and mechanistic attributes are analyzed comprehensively. By incorporating multifunctional supports or rational structural modifications, these systems deliver superior desulfurization efficiency, product selectivity, and recyclability. Despite such progress, commercial deployment is hindered by the following outstanding issues: long-term catalyst durability, continuous-flow reactor design, and full life-cycle cost optimization. Future research should, therefore, focus on elucidating structure–performance relationships, translating batch protocols into robust continuous processes, and performing rigorous environmental and techno-economic assessments to accelerate the industrial adoption of PTC-enabled desulfurization. Full article
(This article belongs to the Special Issue Advanced Catalysis for Energy and a Sustainable Environment)
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14 pages, 572 KiB  
Review
Advancements in Total Knee Arthroplasty over the Last Two Decades
by Jakub Zimnoch, Piotr Syrówka and Beata Tarnacka
J. Clin. Med. 2025, 14(15), 5375; https://doi.org/10.3390/jcm14155375 - 30 Jul 2025
Viewed by 390
Abstract
Total knee arthroplasty is an extensive orthopedic surgery for patients with severe cases of osteoarthritis. This surgery restores the range of motion in the knee joint and allows for pain-free movement. Advancements in medical techniques used in the surgical zone and implant technology, [...] Read more.
Total knee arthroplasty is an extensive orthopedic surgery for patients with severe cases of osteoarthritis. This surgery restores the range of motion in the knee joint and allows for pain-free movement. Advancements in medical techniques used in the surgical zone and implant technology, as well as the management of operations and administration for around two decades prior, have hugely improved surgical outcomes for patients. In this study, advancements in TKA were examined through exploring aspects such as robotic surgery, new implants and materials, minimally invasive surgery, and post-surgery rehabilitation. This paper entails a review of the peer-reviewed literature published between 2005 and 2025 in the PubMed and Google Scholar databases. For predictors, we incorporated clinical relevance together with methodological soundness and relation to review questions to select relevant research articles. We used the PRISMA flowchart to illustrate the article selection system in its entirety. Since robotic surgical and navigation systems have been implemented, surgical accuracy has improved, there is an increased possibility of ensuring alignment, and the use of cementless and 3D-printed implants has increased, offering durable long-term fixation features. The trend in the current literature is that minimally invasive knee surgery (MIS) techniques reduce permanent pain after surgery and length of hospital stays for patients, though the long-term impact still needs to be established. There is various evidence outlining that the enhanced recovery after surgery (ERAS) protocols show positive results in terms of functional recovery and patient satisfaction. The integration of these new advancements enhances TKA surgeries and translates them into ‘need of patient’ procedures, ensuring improved results and increases in patient satisfaction. The aim of this study was to perform a comprehensive analysis of the existing literature regarding TKA advancement studies to identify current gaps and problems. Full article
(This article belongs to the Special Issue Joint Arthroplasties: From Surgery to Recovery)
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12 pages, 248 KiB  
Article
Effectiveness of Targeted Advisory Interventions in Enhancing Welfare on Dairy Farms
by Susy Creatini, Cristina Roncoroni, Federica Salari, Iolanda Altomonte, Giovanni Brajon and Mina Martini
Animals 2025, 15(15), 2197; https://doi.org/10.3390/ani15152197 - 25 Jul 2025
Viewed by 117
Abstract
Animal welfare assessments have raised farmers’ awareness of their management practices, contributing to measurable improvements. However, these protocols often highlight critical points without providing clear guidance on the prioritization of corrective actions. To address this gap, qualified advisory support may play a pivotal [...] Read more.
Animal welfare assessments have raised farmers’ awareness of their management practices, contributing to measurable improvements. However, these protocols often highlight critical points without providing clear guidance on the prioritization of corrective actions. To address this gap, qualified advisory support may play a pivotal role in translating assessments into effective and sustainable interventions. This study evaluates the impact of direct and continuous expert support on improving animal welfare in dairy farms. Data were collected from 21 dairy farms in southeastern Tuscany (Italy) using the Classyfarm (CReNBA) protocol. Each farm underwent two assessments at a three-month interval (T0 and T1), during which tailored support was provided to address specific criticalities. At T0, over 60% of the farms obtained only marginally acceptable welfare scores (mean 67.48 ± 4.75), with major deficiencies in farm management practices, particularly regarding hygiene and space management. At T1, all farms showed substantial improvements, with an average increase of 22% in total welfare scores (mean 82.05 ± 5.71) and a mean of nine improved parameters per farm. These findings underscore the effectiveness of structured, continuous consultancy in not only resolving critical issues but also in fostering more informed, proactive, and sustainable farm management. The direct involvement of experts appears to be a key driver in enhancing both animal welfare and operational outcomes in dairy farming. Full article
(This article belongs to the Section Animal System and Management)
22 pages, 3902 KiB  
Article
Comparative Immunomodulatory Efficacy of Secukinumab and Honokiol in Experimental Asthma and Acute Lung Injury
by Andrei Gheorghe Vicovan, Diana Cezarina Petrescu, Lacramioara Ochiuz, Petru Cianga, Daniela Constantinescu, Elena Iftimi, Mariana Pavel-Tanasa, Codrina Mihaela Ancuta, Cezar-Cătălin Caratașu, Mihai Glod, Carmen Solcan and Cristina Mihaela Ghiciuc
Pharmaceuticals 2025, 18(8), 1108; https://doi.org/10.3390/ph18081108 - 25 Jul 2025
Viewed by 169
Abstract
Background: The study evaluates the immunomodulatory potential of secukinumab (SECU) and honokiol (HONK) in a murine model of allergic asthma complicated by acute lung injury (ALI), with an emphasis on modulating key inflammatory pathways. The rationale is driven by the necessity to attenuate [...] Read more.
Background: The study evaluates the immunomodulatory potential of secukinumab (SECU) and honokiol (HONK) in a murine model of allergic asthma complicated by acute lung injury (ALI), with an emphasis on modulating key inflammatory pathways. The rationale is driven by the necessity to attenuate Th17-mediated cytokine cascades, wherein IL-17 plays a critical role, as well as to explore the adjunctive anti-inflammatory effects of HONK on Th1 cytokine production, including IL-6, TNF-α, and Th2 cytokines. Methods: Mice were sensitized and challenged with ovalbumin (OVA) and lipopolysaccharide (LPS) was administrated to exacerbate pulmonary pathology, followed by administration of SECU, HONK (98% purity, C18H18O2), or their combination. Quantitative analyses incorporated OVA-specific IgE measurements, differential cell counts in bronchoalveolar lavage fluid (BALF), and extensive cytokine profiling in both BALF and lung tissue homogenates, utilizing precise immunoassays and histopathological scoring systems. Results: Both SECU and HONK, when used alone or in combination, display significant immunomodulatory effects in a murine model of allergic asthma concomitant with ALI. The combined therapy synergistically reduced pro-inflammatory mediators, notably Th1 cytokines, such as TNF-α and IL-6, as measured in both BALF and lung tissue homogenates. Conclusions: The combined therapy showed a synergistic attenuation of pro-inflammatory mediators, a reduction in goblet cell hyperplasia, and an overall improvement in lung histoarchitecture. While the data robustly support the merit of a combinatorial approach targeting multiple inflammatory mediators, the study acknowledges limitations in cytokine diffusion and the murine model’s translational fidelity, thereby underscoring the need for further research to optimize clinical protocols for severe respiratory inflammatory disorders. Full article
(This article belongs to the Section Pharmacology)
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55 pages, 4973 KiB  
Review
Zebrafish as a Model Organism for Post-Traumatic Stress Disorder: Insights into Stress Mechanisms and Behavioral Assays
by Alexey Sarapultsev, Maria Komelkova, Oleg Lookin, Sergey Khatsko, Alexander Zhdanov, Stanislav Fedorov, Evgenii Gusev, Alexander Trofimov, Tursonjan Tokay and Desheng Hu
Biology 2025, 14(8), 939; https://doi.org/10.3390/biology14080939 - 25 Jul 2025
Viewed by 286
Abstract
The zebrafish (Danio rerio) has emerged as a powerful model organism for investigating the mechanisms of post-traumatic stress disorder (PTSD), offering unique advantages in translational relevance, genetic trackability, and cost-effectiveness. As a logical continuation of our recent systematic review, this manuscript [...] Read more.
The zebrafish (Danio rerio) has emerged as a powerful model organism for investigating the mechanisms of post-traumatic stress disorder (PTSD), offering unique advantages in translational relevance, genetic trackability, and cost-effectiveness. As a logical continuation of our recent systematic review, this manuscript critically examines the spectrum of experimental strategies used to model PTSD in zebrafish, with a focus on the comparative efficacy and validity of acute, chronic, and complex stress paradigms. Among these, 14–15-day chronic unpredictable stress (CUS/UCS) protocols are identified as the gold standard, reliably inducing core PTSD-like phenotypes—such as anxiety-like behavior, cortisol dysregulation, and neuroinflammatory gene activation. We discuss the influence of environmental, developmental, and genetic factors on stress responses, and highlight the importance of standardized behavioral and molecular endpoints for model validation. While alternative paradigms—including acute, social, pharmacological, and predator-based models—offer mechanistic insights, their translational relevance remains limited without further refinement. We conclude by outlining future directions for zebrafish-based PTSD research, emphasizing the need for protocol harmonization, integration of multi-modal readouts, and exploration of individual variability to enhance the translational value of this model system. Full article
(This article belongs to the Special Issue Social Behavior in Zebrafish)
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18 pages, 2215 KiB  
Article
Exploration of Phosphoproteins in Acinetobacter baumannii
by Lisa Brémard, Sébastien Massier, Emmanuelle Dé, Nicolas Nalpas and Julie Hardouin
Pathogens 2025, 14(8), 732; https://doi.org/10.3390/pathogens14080732 - 24 Jul 2025
Viewed by 348
Abstract
Acinetobacter baumannii is a multidrug-resistant bacterium that has gained significant attention in recent years due to its involvement in a growing number of hospital-acquired infections. The World Health Organization has classified it as a critical priority pathogen, underscoring the urgent need for new [...] Read more.
Acinetobacter baumannii is a multidrug-resistant bacterium that has gained significant attention in recent years due to its involvement in a growing number of hospital-acquired infections. The World Health Organization has classified it as a critical priority pathogen, underscoring the urgent need for new therapeutic strategies. Post-translational modifications (PTMs), such as phosphorylation, play essential roles in various bacterial processes, including antibiotic resistance, virulence or biofilm formation. Although proteomics has increasingly enabled their characterization, the identification of phosphorylated peptides remains challenging, primarily due to the enrichment procedures. In this study, we focused on characterizing serine, threonine, and tyrosine phosphorylation in the A. baumannii ATCC 17978 strain. We optimized three parameters for phosphopeptide enrichment using titanium dioxide (TiO2) beads (number of enrichment fractions between the phosphopeptides and TiO2 beads, the quantity peptides and type of loading buffer) to determine the most effective conditions for maximizing phosphopeptide identification. Using this optimized protocol, we identified 384 unique phosphorylation sites across 241 proteins, including 260 novel phosphosites previously unreported in A. baumannii. Several of these phosphorylated proteins are involved in critical bacterial processes such as antimicrobial resistance, biofilm formation or pathogenicity. We discuss these proteins, focusing on the potential functional implications of their phosphorylation. Notably, we identified 34 phosphoproteins with phosphosites localized at functional sites, such as active sites, multimer interfaces, or domains important for structural integrity. Our findings significantly expand the current phosphoproteomic landscape of A. baumannii and support the hypothesis that PTMs, particularly phosphorylation, play a central regulatory role in its physiology and pathogenic potential. Full article
(This article belongs to the Section Bacterial Pathogens)
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16 pages, 5151 KiB  
Article
Design and Characterization of Curcumin-Modified Polyurethane Material with Good Mechanical, Shape-Memory, pH-Responsive, and Biocompatible Properties
by Man Wang, Hongying Liu, Wei Zhao, Huafen Wang, Yuwei Zhuang, Jie Yang, Zhaohui Liu, Jing Zhu, Sichong Chen and Jinghui Cheng
Biomolecules 2025, 15(8), 1070; https://doi.org/10.3390/biom15081070 - 24 Jul 2025
Viewed by 236
Abstract
In the context of critical challenges in curcumin-modified polyurethane synthesis—including limited curcumin bioavailability and suboptimal biodegradability/biocompatibility—a novel polyurethane material (Cur-PU) with good mechanical, shape memory, pH-responsive, and biocompatibility was synthesized via a one-pot, two-step synthetic protocol in which HO-PCL-OH served as the soft [...] Read more.
In the context of critical challenges in curcumin-modified polyurethane synthesis—including limited curcumin bioavailability and suboptimal biodegradability/biocompatibility—a novel polyurethane material (Cur-PU) with good mechanical, shape memory, pH-responsive, and biocompatibility was synthesized via a one-pot, two-step synthetic protocol in which HO-PCL-OH served as the soft segment and curcumin was employed as the chain extender. The experimental results demonstrate that with the increase in Cur units, the crystallinity of the Cur-PU material decreases from 32.6% to 5.3% and that the intensities of the diffraction peaks at 2θ = 21.36°, 21.97°, and 23.72° in the XRD pattern gradually diminish. Concomitantly, tensile strength decreased from 35.5 MPa to 19.3 MPa, and Shore A hardness declined from 88 HA to 65 HA. These observations indicate that the sterically hindered benzene ring structure of Cur imposes restrictions on HO-PCL-OH crystallization, leading to lower crystallinity and retarded crystallization kinetics in Cur-PU. As a consequence, the material’s tensile strength and hardness are diminished. Except for the Cur-PU-3 sample, all other variants exhibited exceptional shape-memory functionality, with Rf and Rr exceeding 95%, as determined by three-point bending method. Analogous to pure curcumin solutions, Cur-PU solutions demonstrated pH-responsive chromatic transitions: upon addition of hydroxide ion (OH) solutions at increasing concentrations, the solutions shifted from yellow-green to dark green and finally to orange-yellow, enabling sensitive pH detection across alkaline gradients. Hydrolytic degradation studies conducted over 15 weeks in air, UPW, and pH 6.0/8.0 phosphate buffer solutions revealed mass loss <2% for Cur-PU films. Surface morphological analysis showed progressive etching with the formation of micro-to-nano-scale pores, indicative of a surface-erosion degradation mechanism consistent with pure PCL. Biocompatibility assessments via L929 mouse fibroblast co-culture experiments demonstrated ≥90% cell viability after 72 h, while relative red blood cell hemolysis rates remained below 5%. Collectively, these findings establish Cur-PU as a biocompatible material with tunable mechanical properties, and pH responsiveness, underscoring its translational potential for biomedical applications such as drug delivery systems and tissue engineering scaffolds. Full article
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40 pages, 1654 KiB  
Review
Bioactive Plant-Derived Compounds as Novel Perspectives in Oral Cancer Alternative Therapy
by Gabriela Mitea, Verginica Schröder and Irina Mihaela Iancu
Pharmaceuticals 2025, 18(8), 1098; https://doi.org/10.3390/ph18081098 - 24 Jul 2025
Viewed by 392
Abstract
Background: Oral squamous cell carcinoma (OSCC) is one of the most serious forms of cancer in the world. The opportunities to decrease the mortality rate would lie in the possibility of earlier identification of this pathology, and at the same time, the immediate [...] Read more.
Background: Oral squamous cell carcinoma (OSCC) is one of the most serious forms of cancer in the world. The opportunities to decrease the mortality rate would lie in the possibility of earlier identification of this pathology, and at the same time, the immediate approach of anticancer therapy. Furthermore, new treatment strategies for OSCC are needed to improve existing therapeutic options. Bioactive compounds found in medicinal plants could be used to support these strategies. It is already known that they have an increased potential for action and a safety profile; therefore, they could improve the therapeutic effect of classical chemotherapeutic agents in combination therapies. Methodology: This research was based on an extensive review of recently published studies in scientific databases (PubMed, Scopus, and Web of Science). The selection criteria were based on experimental protocols investigating molecular mechanisms, synergistic actions with conventional anticancer agents, and novel formulation possibilities (e.g., nanoemulsions and mucoadhesive films) for the targeted delivery of bioactive compounds in OSCC. Particular attention was given to in vitro, in vivo, translational, and clinical studies that have proven therapeutic relevance. Results: Recent discoveries regarding the effect of bioactive compounds in the treatment of oral cancer were analyzed, with a view to integrating them into oncological practice for increasing therapeutic efficacy and reducing the occurrence of adverse reactions and treatment resistance. Conclusions: Significant progress has been achieved in this review, allowing us to appreciate that the valorization of these bioactive compounds is emerging. Full article
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13 pages, 1301 KiB  
Article
Translational Pitfalls in SCI Bladder Research: The Hidden Role of Urinary Drainage Techniques in the Rat Model
by Sophina Bauer, Michael Kleindorfer, Karin Roider, Evelyn Beyerer, Martha Georgina Brandtner, Peter Törzsök, Lukas Lusuardi, Ludwig Aigner and Elena Esra Keller
Biology 2025, 14(8), 928; https://doi.org/10.3390/biology14080928 - 23 Jul 2025
Viewed by 274
Abstract
Spinal cord injury (SCI) frequently leads to neurogenic lower urinary tract dysfunction, for which appropriate bladder management is essential. While clinical care relies on continuous low-pressure drainage in the acute phase, rat models commonly use twice-daily manual bladder expression—a method known to generate [...] Read more.
Spinal cord injury (SCI) frequently leads to neurogenic lower urinary tract dysfunction, for which appropriate bladder management is essential. While clinical care relies on continuous low-pressure drainage in the acute phase, rat models commonly use twice-daily manual bladder expression—a method known to generate high intravesical pressures and retention. This study evaluated the impact of this standard practice on bladder tissue remodeling by comparing it to continuous drainage via high vesicostomy in a rat SCI model. 32 female Lewis rats underwent thoracic contusion SCI and were assigned to either manual expression or vesicostomy-based bladder management. Over eight weeks, locomotor recovery, wound healing, and bladder histology were assessed. Vesicostomy proved technically simple but required tailored wound care and calibration. Results showed significantly greater bladder wall thickness, detrusor muscle hypertrophy, urothelial thickening, collagen deposition, and mast cell infiltration in the manual expression group compared to both vesicostomy and controls. In contrast, vesicostomy animals exhibited near-control levels across most parameters. These findings highlight that commonly used bladder emptying protocols in rat SCI models may overestimate structural bladder changes and inflammatory responses. Refined drainage strategies such as vesicostomy can minimize secondary damage and improve the translational relevance of preclinical SCI research. Full article
(This article belongs to the Special Issue Advances in the Fields of Neurotrauma and Neuroregeneration)
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35 pages, 1752 KiB  
Review
Recent Advances in Biodegradable Magnesium Alloys for Medical Implants: Evolution, Innovations, and Clinical Translation
by Mykyta Aikin, Vadim Shalomeev, Volodymyr Kukhar, Andrii Kostryzhev, Ihor Kuziev, Viktoriia Kulynych, Oleksandr Dykha, Volodymyr Dytyniuk, Oleksandr Shapoval, Alvydas Zagorskis, Vadym Burko, Olha Khliestova, Viacheslav Titov and Oleksandr Hrushko
Crystals 2025, 15(8), 671; https://doi.org/10.3390/cryst15080671 - 23 Jul 2025
Viewed by 613
Abstract
Biodegradable magnesium alloys have emerged as promising alternatives to permanent metallic implants due to their unique combination of mechanical compatibility with bone and complete resorption, addressing the persistent issues of stress shielding and secondary removal surgeries. This review critically examines the historical development [...] Read more.
Biodegradable magnesium alloys have emerged as promising alternatives to permanent metallic implants due to their unique combination of mechanical compatibility with bone and complete resorption, addressing the persistent issues of stress shielding and secondary removal surgeries. This review critically examines the historical development of magnesium-based biomaterials, highlighting advances in alloy design, manufacturing processes, and surface engineering that now enable tailored degradation and improved clinical performance. Drawing on recent clinical and preclinical studies, we summarize improvements in corrosion resistance, mechanical properties, and biocompatibility that have supported the clinical translation of magnesium alloys across a variety of orthopedic and emerging medical applications. However, challenges remain, including unpredictable in vivo degradation kinetics, limited long-term safety data, lack of standardized testing protocols, and ongoing regulatory uncertainties. We conclude that while magnesium-based biomaterials have advanced from experimental concepts to clinically validated solutions, further progress in personalized degradation control, real-time monitoring, and harmonized regulatory frameworks is needed to fully realize their transformative clinical potential. Full article
(This article belongs to the Special Issue Development of Light Alloys and Their Applications)
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54 pages, 12628 KiB  
Review
Cardiac Mechano-Electrical-Fluid Interaction: A Brief Review of Recent Advances
by Jun Xu and Fei Wang
Eng 2025, 6(8), 168; https://doi.org/10.3390/eng6080168 - 22 Jul 2025
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Abstract
This review investigates recent developments in cardiac mechano-electrical-fluid interaction (MEFI) modeling, with a focus on multiphysics simulation platforms and digital twin frameworks developed between 2015 and 2025. The purpose of the study is to assess how computational modeling methods—particularly finite element and immersed [...] Read more.
This review investigates recent developments in cardiac mechano-electrical-fluid interaction (MEFI) modeling, with a focus on multiphysics simulation platforms and digital twin frameworks developed between 2015 and 2025. The purpose of the study is to assess how computational modeling methods—particularly finite element and immersed boundary techniques, monolithic and partitioned coupling schemes, and artificial intelligence (AI)-enhanced surrogate modeling—capture the integrated dynamics of cardiac electrophysiology, tissue mechanics, and hemodynamics. The goal is to evaluate the translational potential of MEFI models in clinical applications such as cardiac resynchronization therapy (CRT), arrhythmia classification, atrial fibrillation ablation, and surgical planning. Quantitative results from the literature demonstrate <5% error in pressure–volume loop predictions, >0.90 F1 scores in machine-learning-based arrhythmia detection, and <10% deviation in myocardial strain relative to MRI-based ground truth. These findings highlight both the promise and limitations of current MEFI approaches. While recent advances improve physiological fidelity and predictive accuracy, key challenges remain in achieving multiscale integration, model validation across diverse populations, and real-time clinical applicability. The review concludes by identifying future milestones for clinical translation, including regulatory model certification, standardization of validation protocols, and integration of patient-specific digital twins into electronic health record (EHR) systems. Full article
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