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14 pages, 1372 KiB  
Article
Risk Factors of Histopathological Crescent Formation in Pediatric IgA Vasculitis Nephritis
by Yanyan Jin, Yi Xie, Qian Lin, Yu Zhu, Limin Huang, Yang He and Haidong Fu
Medicina 2025, 61(8), 1421; https://doi.org/10.3390/medicina61081421 - 6 Aug 2025
Abstract
Background and Objectives: This study aimed to explore the risk factors of histopathological crescent formation in pediatric IgA vasculitis nephritis (IgAVN). Materials and Methods: Enrolled patients with biopsy-proven IgAVN from Zhejiang University’s hospital were split into two groups: 377 with no [...] Read more.
Background and Objectives: This study aimed to explore the risk factors of histopathological crescent formation in pediatric IgA vasculitis nephritis (IgAVN). Materials and Methods: Enrolled patients with biopsy-proven IgAVN from Zhejiang University’s hospital were split into two groups: 377 with no crescents on histopathology (Group 1) and 364 with crescentic nephritis (Group 2). Collected data included clinical features, lab indicators, histopathological grading, and factors causing glomerular sclerosis. Logistic regression was used to assess factors affecting crescent formation in IgAVN. Double-immunofluorescence assay was used to detect TGF-β1, MCP-1, α-SMA, Collagen I, and FN1 in kidney biopsy specimens. The relationship between kidney fibrosis factors and histopathological grade were analyzed using Chi-square and Pearson tests. Results: A total of 741 patients with IgAVN were included in the study. Univariate logistic regression identified potential factors related to crescent formation, including age, gender, clinical classification, hematuria grade, 24 h urine protein level, peripheral white blood cells (WBCs), serum albumin, Cystatin-C, APTT, and PT. Multivariate analysis revealed statistical significance for age, 24 h urine protein, and WBCs across pathological grades (p < 0.05). Mantel–Haenszel Chi-square tests indicated a linear relationship between IgAVN pathological grade and α-SMA, TGF-β1, MCP-1, and FN1. Pearson correlation analysis confirmed a positive correlation between pathological grade and these markers. Conclusions: Age, 24 h urinary protein, and blood WBCs are identified as risk factors for histopathological crescent formation in children with IgAVN. Additionally, a higher pathological grade is associated with more pronounced fibrosis indicators. Full article
(This article belongs to the Section Pediatrics)
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23 pages, 2059 KiB  
Systematic Review
Comparative Effectiveness of Nutritional Supplements in the Treatment of Knee Osteoarthritis: A Network Meta-Analysis
by Yuntong Zhang, Yunfei Gui, Roger Adams, Joshua Farragher, Catherine Itsiopoulos, Keegan Bow, Ming Cai and Jia Han
Nutrients 2025, 17(15), 2547; https://doi.org/10.3390/nu17152547 - 3 Aug 2025
Viewed by 277
Abstract
Background: Knee osteoarthritis (KOA) is a prevalent degenerative joint disease that can greatly affect quality of life in middle-aged and elderly individuals. Nutritional supplements are increasingly used for KOA due to their low risk, but direct comparative evidence on their efficacy and [...] Read more.
Background: Knee osteoarthritis (KOA) is a prevalent degenerative joint disease that can greatly affect quality of life in middle-aged and elderly individuals. Nutritional supplements are increasingly used for KOA due to their low risk, but direct comparative evidence on their efficacy and safety remains scarce. This study aimed to systematically compare the effectiveness and safety of seven common nutritional supplements for KOA. Methods: A systematic review and network meta-analysis were conducted following PRISMA guidelines. Embase, PubMed, and the Cochrane Library were searched through December 2024 for randomized controlled trials (RCTs) evaluating use of eggshell membrane, vitamin D, Boswellia, curcumin, ginger, krill oil, or collagen, versus placebo, in adults with KOA. Primary outcomes included changes in scores for WOMAC pain, stiffness and function, and pain visual analog scale (VAS). Adverse events were also assessed. Bayesian network meta-analyses estimated ranking probabilities for each intervention. Results: In total, 39 RCTs (42 studies; 4599 patients) were included. Compared with placebo, Boswellia showed significant improvements in WOMAC pain (mean difference [MD] = 10.58, 95% CI: 6.45 to 14.78, p < 0.05), stiffness (MD = 9.47, 95% CI: 6.39 254 to 12.74, p < 0.05), function (MD = 14.00, 95% CI: 7.74 to 20.21, p < 0.05), and VAS pain (MD = 17.26, 95% CI: 8.06 to 26.52, p < 0.05). Curcumin, collagen, ginger, and krill oil also demonstrated benefits in some outcomes. No supplement was associated with increased adverse events compared to placebo. Bayesian rankings indicated Boswellia had the highest probability of being most effective for pain and stiffness, with krill oil and curcumin showing potential for function improvement. Conclusions: Nutritional supplements, particularly Boswellia, appear to be effective and well-tolerated for improving KOA symptoms and function. These results suggest that certain supplements may be useful as part of non-pharmacological KOA management. However, further large-scale, well-designed randomized controlled trials (RCTs) are needed to confirm these findings, particularly those that include more standardized dosages and formulations, as well as to evaluate their long-term efficacy. Full article
(This article belongs to the Section Nutrition Methodology & Assessment)
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23 pages, 4116 KiB  
Article
Taxonomic and Functional Profiling of Bacterial Communities in Leather Biodegradation: Insights into Metabolic Pathways and Diversity
by Manuela Bonilla-Espadas, Marcelo Bertazzo, Irene Lifante-Martinez, Mónica Camacho, Elena Orgilés-Calpena, Francisca Arán-Aís and María-José Bonete
Bacteria 2025, 4(3), 37; https://doi.org/10.3390/bacteria4030037 - 1 Aug 2025
Viewed by 103
Abstract
Leather biodegradation is a complex microbial process with increasing relevance for sustainable waste management. In this study, we investigated bacterial communities responsible for the degradation of leather treated with different tanning agents (chrome, Zeolite, Biole®) using high-throughput 16S rRNA gene sequencing [...] Read more.
Leather biodegradation is a complex microbial process with increasing relevance for sustainable waste management. In this study, we investigated bacterial communities responsible for the degradation of leather treated with different tanning agents (chrome, Zeolite, Biole®) using high-throughput 16S rRNA gene sequencing and metatranscriptomic analysis. Proteobacteria, Bacteroidetes, and Patescibacteria emerged as the dominant phyla, while genera such as Acinetobacter, Pseudomonas, and Sphingopyxis were identified as key contributors to enzymatic activity and potential metal resistance. A total of 1302 enzymes were expressed across all the conditions, including 46 proteases, with endopeptidase La, endopeptidase Clp, and methionyl aminopeptidase being the most abundant. Collagen samples exhibited the highest functional diversity and total enzyme expression, whereas chrome-treated samples showed elevated protease activity, indicating selective pressure from heavy metals. Differential enzyme expression patterns were linked to both the microbial identity and tanning chemistry, revealing genus- and treatment-specific enzymatic signatures. These findings deepen our understanding of how tanning agents modulate the microbial structure and function and identify proteases with potential applications in the bioremediation and eco-innovation of leather waste processing. Full article
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27 pages, 5071 KiB  
Article
Immunohistochemical and Ultrastructural Study of the Degenerative Processes of the Hip Joint Capsule and Acetabular Labrum
by Riana Maria Huzum, Bogdan Huzum, Marius Valeriu Hînganu, Ludmila Lozneanu, Fabian Cezar Lupu and Delia Hînganu
Diagnostics 2025, 15(15), 1932; https://doi.org/10.3390/diagnostics15151932 - 31 Jul 2025
Viewed by 247
Abstract
Background/Objectives: Degenerative processes of the hip joint increasingly affect not only the articular cartilage but also periarticular structures such as the joint capsule and acetabular labrum. This study aimed to investigate the structural and molecular changes occurring in these tissues during advanced [...] Read more.
Background/Objectives: Degenerative processes of the hip joint increasingly affect not only the articular cartilage but also periarticular structures such as the joint capsule and acetabular labrum. This study aimed to investigate the structural and molecular changes occurring in these tissues during advanced hip osteoarthritis. Methods: A combined analysis using immunohistochemistry (IHC), scanning electron microscopy (SEM), and micro-computed tomography (microCT) was conducted on tissue samples from patients undergoing total hip arthroplasty and from controls with morphologically normal joints. Markers associated with proliferation (Ki67), inflammation (CD68), angiogenesis (CD31, ERG), chondrogenesis (SOX9), and lubrication (Lubricin) were evaluated. Results: The pathological group showed increased expression of Ki67, CD68, CD31, ERG, and SOX9, with a notable decrease in Lubricin. SEM analysis revealed ultrastructural disorganization, collagen fragmentation, and neovascular remodeling in degenerative samples. A significant correlation between structural damage and molecular expression was identified. Conclusions: These results suggest that joint capsule and acetabular labrum degeneration are interconnected and reflect a broader pathophysiological continuum, supporting the use of integrated IHC and SEM profiling for early detection and targeted intervention in hip joint disease. Full article
(This article belongs to the Special Issue Diagnosis and Management of Osteoporosis)
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13 pages, 570 KiB  
Review
Examples of Underexploited Marine Organisms in Cosmeceutical Applications
by Céline Couteau and Laurence Coiffard
Mar. Drugs 2025, 23(8), 305; https://doi.org/10.3390/md23080305 - 30 Jul 2025
Viewed by 291
Abstract
A number of marine resources have been exploited for a long time. Examples include Fucus and Laminaria, from which gelling agents are extracted. Only a few hundred thousand marine species are currently known, representing a tiny fraction of the estimated total of [...] Read more.
A number of marine resources have been exploited for a long time. Examples include Fucus and Laminaria, from which gelling agents are extracted. Only a few hundred thousand marine species are currently known, representing a tiny fraction of the estimated total of between 700,000 and one million species. This opens up numerous possibilities for innovation in the cosmetics industry. In this study, we present various species that are currently under-exploited, but which could have applications in hydration and photoprotection, for example. Algae and microalgae are worthy of interest because they can be used for hydration and anti-ageing purposes. Collagen can be extracted from animal sources and used as a substitute for collagen of bovine origin. From a marketing perspective, it is possible to market it as ‘marine collagen’. However, it is imperative to emphasize the significance of ensuring the sustainability of the resource. In accordance with this imperative, algae that are capable of being cultivated are distinguished by their enhanced qualities. Full article
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14 pages, 846 KiB  
Article
Uncovering Allele-Specific Expression Patterns Associated with Sea Lice (Caligus rogercresseyi) Burden in Atlantic Salmon
by Pablo Cáceres, Paulina López, Carolina Araya, Daniela Cichero, Liane N. Bassini and José M. Yáñez
Genes 2025, 16(7), 841; https://doi.org/10.3390/genes16070841 - 19 Jul 2025
Viewed by 385
Abstract
Background/Objetives: Sea lice (Caligus rogercresseyi) pose a major threat to Atlantic salmon (Salmo salar) aquaculture by compromising fish health and reducing production efficiency. While genetic variation in parasite load has been reported, the molecular mechanisms underlying this variation remain [...] Read more.
Background/Objetives: Sea lice (Caligus rogercresseyi) pose a major threat to Atlantic salmon (Salmo salar) aquaculture by compromising fish health and reducing production efficiency. While genetic variation in parasite load has been reported, the molecular mechanisms underlying this variation remain unclear. Methods: two sea lice challenge trials were conducted, achieving high infestation rates (47.5% and 43.5%). A total of 85 fish, selected based on extreme phenotypes for lice burden (42 low, 43 high), were subjected to transcriptomic analysis. Differential gene expression was integrated with allele-specific expression (ASE) analysis to uncover cis-regulatory variation influencing host response. Results: Sixty genes showed significant ASE (p < 0.05), including 33 overexpressed and 27 underexpressed. Overexpressed ASE genes included Keratin 15, Collagen IV/V, TRIM16, and Angiopoietin-1-like, which are associated with epithelial integrity, immune response, and tissue remodeling. Underexpressed ASE genes such as SOCS3, CSF3R, and Neutrophil cytosolic factor suggest individual variation in cytokine signaling and oxidative stress pathways. Conclusions: several ASE genes co-localized with previously identified QTLs for sea lice resistance, indicating that cis-regulatory variants contribute to phenotypic differences in parasite susceptibility. These results highlight ASE analysis as a powerful tool to identify functional regulatory elements and provide valuable candidates for selective breeding and genomic improvement strategies in aquaculture. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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17 pages, 3718 KiB  
Article
Pharmacological Immunomodulation via Collagen–Polyvinylpyrrolidone or Pirfenidone Plays a Role in the Recovery of Patients with Severe COVID-19 Through Similar Mechanisms of Action Involving the JAK/STAT Signalling Pathway: A Pilot Study
by Hugo Mendieta-Zerón, Esteban Cruz-Arenas, Salvador Díaz-Meza, Alejandro Cabrera-Wrooman, Edna Ayerim Mandujano-Tinoco, Rosa M. Salgado, Hugo Tovar, Daniel Muñiz-García, Laura Julieta Orozco-Castañeda, Sonia Hernández-Enríquez, Miriam Deyanira Rodríguez-Piña, Ana Sarahí Mulia-Soto, José Meneses-Calderón, Paul Mondragón-Terán and Edgar Krötzsch
Adv. Respir. Med. 2025, 93(4), 24; https://doi.org/10.3390/arm93040024 - 18 Jul 2025
Viewed by 590
Abstract
The therapeutic target of COVID-19 is focused on controlling inflammation and preventing fibrosis. Collagen–polyvinylpyrrolidone (collagen-PVP) and pirfenidone both have the ability to control the cytokine storm observed in rheumatic and fibrotic disorders. In this work, our aim was to understand the benefits of [...] Read more.
The therapeutic target of COVID-19 is focused on controlling inflammation and preventing fibrosis. Collagen–polyvinylpyrrolidone (collagen-PVP) and pirfenidone both have the ability to control the cytokine storm observed in rheumatic and fibrotic disorders. In this work, our aim was to understand the benefits of treatment with each of these drugs in patients with severe COVID-19. In total, 36 patients were treated with dexamethasone and enoxaparin, but 26 were allocated collagen-PVP or pirfenidone (n = 15 and 11, respectively); the clinical and metabolic effects were compared among them. Since pirfenidone works via transcriptional mechanisms, we performed a human genome microarray assay using RNA isolated from fibroblast and monocyte cultures treated with the biodrug, with the aim of hypothesising a possible mechanism of action for collagen-PVP. Our results showed that hospital stay duration, quick COVID-19 severity index (qCSI), and admission to the intensive care unit were statistically significantly lower (p < 0.02) in patients treated with collagen-PVP or pirfenidone when compared with the control group, and that only collagen-PVP normalised serum glucose at discharge. Ingenuity Pathway Analysis showed that the cell cycle, inflammation, and cell surface–extracellular matrix interactions could be regulated with collagen-PVP via the downmodulation of proinflammatory cytokines, while Th2 anti-inflammatory response signalling could be upregulated. Furthermore, the downregulation of some of the genes involved in nitric oxide production showed a possible control for JAK in the IFN-γ pathway, allowing for the possibility of controlling inflammation through the JAK/STAT pathway, as has been observed for pirfenidone and other immunomodulators, such as ruxolitinib. Full article
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14 pages, 8113 KiB  
Article
Cellular and Matrix Organisation of the Human Aortic Valve Interleaflet Triangles
by Najma Latif, Padmini Sarathchandra, Albaraa Al-Holy, Sanida Vaz, Adrian H. Chester and Magdi H. Yacoub
Biology 2025, 14(7), 863; https://doi.org/10.3390/biology14070863 - 16 Jul 2025
Viewed by 206
Abstract
(1) Background: The sophisticated function of the aortic root relies on the coordinated movement of its constituent components. This study examines the extracellular components of the interleaflet triangles (ILTs) and characterises the cells that are present within this region of the aortic root. [...] Read more.
(1) Background: The sophisticated function of the aortic root relies on the coordinated movement of its constituent components. This study examines the extracellular components of the interleaflet triangles (ILTs) and characterises the cells that are present within this region of the aortic root. (2) Methods: A total of 10 human aortic valves and 6 porcine aortic valves were processed for immunohistochemical staining, scanning, and transmission electron microscopy. (3) Results: The three ILTs differed in size and macroscopic appearance. Each triangle comprised up to five distinct layers of tissue: an innermost endothelial layer, an inner elastin-rich layer, a thicker outer layer comprising densely packed layers of collagen and glycosaminoglycans, and an outer layer of intermingled myocardial and adipose tissue. A band of cells near the luminal surfaces of all ILTs expressed smooth muscle cell α-actin with variable expression of smooth muscle myosin heavy chain. In all the ILTs, there was evidence of neurofilament staining, indicating the presence of nerve fibres. (4) Conclusions: Each ILT is unique in its structure and organisation, with differing amounts of elastin and collagen, as well as myocardial, adipose, and fibrous content. The ILTs contain multiple cell types in varying abundance. Functional studies are required to determine the role of the different cells and their organisation in contributing to the sophisticated, dynamic behaviour of the aortic root. Full article
(This article belongs to the Section Cell Biology)
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18 pages, 1054 KiB  
Article
Dry-Cured Bísaro Ham: Differences in Physicochemical Characteristics, Fatty Acid Profile and Volatile Compounds Between Muscles
by Lia Vasconcelos, Luís G. Dias, Ana Leite, José M. Lorenzo, Alfredo Teixeira, Sandra S. Q. Rodrigues and Javier Mateo
Foods 2025, 14(14), 2474; https://doi.org/10.3390/foods14142474 - 15 Jul 2025
Viewed by 1133
Abstract
The aim of this study was to evaluate differences in the physicochemical characteristics, fatty acid profiles and volatile compounds of different muscle types (semimembranosus (SM), biceps femoris (BF) and semitendinosus (ST)) used to produce dry-cured Bísaro ham. Sixteen dry-cured hams were used. [...] Read more.
The aim of this study was to evaluate differences in the physicochemical characteristics, fatty acid profiles and volatile compounds of different muscle types (semimembranosus (SM), biceps femoris (BF) and semitendinosus (ST)) used to produce dry-cured Bísaro ham. Sixteen dry-cured hams were used. The physicochemical parameters were significantly affected by the muscle type, with the differences being mainly related to the different drying degrees and the intramuscular fat and collagen contents of the fresh muscles. Additionally, the type of muscle had a significant influence on the polyunsaturated fatty acids, such that the muscle with the highest fat content (ST) had the lowest PUFA content and vice versa. There were strong significant differences in the total content of volatile compounds derived from the Strecker reaction, which was higher in the ST muscle, and in the proportions of these compounds with different functional groups. The amount of sulfur compounds was also affected by the muscle type and was higher in the SM muscle. Due to the great impact of Strecker-derived and sulfur compounds on the flavor of the cured hams, these differences would affect the flavor perception of the different muscles. The variability between muscles in composition, fatty acids and volatile compounds allowed for discrimination of the samples by muscle type using multivariate analysis. Full article
(This article belongs to the Special Issue Conventional and Emerging Technologies for Meat Processing)
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12 pages, 869 KiB  
Article
Perioperative Profiling of a Disintegrin and Metalloprotease with Thrombospondin Type 1 Motif, Member 13 (ADAMTS13) Activity in Cardiac Surgery: Kinetics and Mechanistic Insights
by Bernhard Strasser, Johann Knotzer, Selina Sartori, Bernhard Poidinger, Oskar Kotzinger, Christian Irsara, Gerald Lirk, Carolin Gunz and Alexander Haushofer
J. Clin. Med. 2025, 14(14), 4936; https://doi.org/10.3390/jcm14144936 - 11 Jul 2025
Viewed by 320
Abstract
Background: The enzyme A Disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) regulates hemostasis by cleaving von Willebrand factor (VWF) multimers. ADAMTS13–VWF axis dysregulation leads to different thrombotic conditions. This study investigated changes in ADAMTS13 activity during major cardiac procedures [...] Read more.
Background: The enzyme A Disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) regulates hemostasis by cleaving von Willebrand factor (VWF) multimers. ADAMTS13–VWF axis dysregulation leads to different thrombotic conditions. This study investigated changes in ADAMTS13 activity during major cardiac procedures and their relationship to VWF changes and clinical complications. Methods: A total of 628 ADAMTS13 activity and inhibitor measurements were carried out in 168 patients who underwent cardiac surgery. ADAMTS13 activity was measured after the initiation of anesthesia and daily for up to 6 days postoperatively via Technozym chromogenic ELISA. The von Willebrand factor antigen (VWF:Ag) and collagen binding (VWF:CB) were also measured. Clinical complications and correlations with liver function biomarkers were also assessed. Results: ADAMTS13 activity significantly decreased during surgery, with mean values markedly decreasing from preoperative to postoperative measurements (p = 0.01). A clear inverse relationship between ADAMTS13 activity and the VWF:CB/VWF:AG ratio was observed, indicating that increased high-molecular-weight VWF multimers are associated with decreased ADAMTS13 activity. Correlation analyses (CHE, Spearman’s rho = 0.39) indicated that the reduction in ADAMTS13 activity was not attributable to impaired liver synthesis but likely resulted from peripheral consumption, potentially influenced by surgical stress. Conclusions: Perioperative reductions in ADAMTS13 activity are associated with an accumulation of high-molecular-weight VWF multimers and a higher incidence of postoperative complications. These results demonstrate that ADAMTS13 could be a useful perioperative risk biomarker for cardiac surgery patients. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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17 pages, 1960 KiB  
Article
Radiographic Evidence of Immature Bone Architecture After Sinus Grafting: A Multidimensional Image Analysis Approach
by Ibrahim Burak Yuksel, Fatma Altiparmak, Gokhan Gurses, Ahmet Akti, Merve Alic and Selin Tuna
Diagnostics 2025, 15(14), 1742; https://doi.org/10.3390/diagnostics15141742 - 9 Jul 2025
Viewed by 354
Abstract
Background: Radiographic evaluation of bone regeneration following maxillary sinus floor elevation commonly emphasizes volumetric gains. However, the qualitative microarchitecture of the regenerated bone, particularly when assessed via two-dimensional imaging modalities, such as panoramic radiographs, remains insufficiently explored. This study aimed to evaluate early [...] Read more.
Background: Radiographic evaluation of bone regeneration following maxillary sinus floor elevation commonly emphasizes volumetric gains. However, the qualitative microarchitecture of the regenerated bone, particularly when assessed via two-dimensional imaging modalities, such as panoramic radiographs, remains insufficiently explored. This study aimed to evaluate early trabecular changes in grafted maxillary sinus regions using fractal dimension, first-order statistics, and gray-level co-occurrence matrix analysis. Methods: This retrospective study included 150 patients who underwent maxillary sinus floor augmentation with bovine-derived xenohybrid grafts. Postoperative panoramic radiographs were analyzed at 6 months to assess early healing. Four standardized regions of interest representing grafted sinus floors and adjacent tuberosity regions were analyzed. Image processing and quantitative analyses were performed to extract fractal dimension (FD), first-order statistics (FOS), and gray-level co-occurrence matrix (GLCM) features (contrast, homogeneity, energy, correlation). Results: A total of 150 grafted sites and 150 control tuberosity sites were analyzed. Fractal dimension (FD) and contrast values were significantly lower in grafted areas than in native tuberosity bone (p < 0.001 for both), suggesting reduced trabecular complexity and less distinct transitions. In contrast, higher homogeneity (p < 0.001) and mean gray-level intensity values (p < 0.001) were observed in the grafted regions, reflecting a more uniform but immature trabecular pattern during the early healing phase. Energy and correlation values also differed significantly between groups (p < 0.001). No postoperative complications were reported, and resorbable collagen membranes appeared to support graft stability. Conclusions: Although the grafted sites demonstrated radiographic volume stability, their trabecular architecture remained immature at 6 months, implying that volumetric measurements alone may be insufficient to assess biological bone maturation. These results support the utility of advanced textural and fractal analysis in routine imaging to optimize clinical decision-making regarding implant placement timing in grafted sinuses. Full article
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17 pages, 740 KiB  
Systematic Review
Accompanying Titanium Meshes and Titanium-Reinforced Membranes with Collagen Membranes in Vertical Alveolar Ridge Augmentations: A Systematic Review
by Amir-Ali Yousefi-Koma, Reza Amid, Anahita Moscowchi, Hanieh Nokhbatolfoghahaei and Mahdi Kadkhodazadeh
J. Funct. Biomater. 2025, 16(7), 246; https://doi.org/10.3390/jfb16070246 - 4 Jul 2025
Viewed by 752
Abstract
Background: Vertical ridge augmentations (VRAs), including guided bone regeneration (GBR) techniques, have been utilized in the reconstruction of deficient alveolar ridges for quite some time. GBR-based VRA procedures are technique-sensitive, operator-dependent, and often lead to complications detected during or after the treatment. The [...] Read more.
Background: Vertical ridge augmentations (VRAs), including guided bone regeneration (GBR) techniques, have been utilized in the reconstruction of deficient alveolar ridges for quite some time. GBR-based VRA procedures are technique-sensitive, operator-dependent, and often lead to complications detected during or after the treatment. The main objective of this systematic review was to include randomized and non-randomized human studies that investigated the regenerative outcome differences, as well as the incidence rates of healing and surgical complications of titanium meshes and/or titanium-reinforced membranes with and without collagen membranes utilized in GBR-based VRA. Methods: This systematic review has been prepared and organized according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines and is registered at PROSPERO (Registration ID: CRD420251002615). Medline via PubMed, Scopus, Web of Science, Embase, and the Cochrane Library were searched for eligible studies up to 5 June 2025. Randomized and non-randomized human clinical studies, except for case reports, focused on applying titanium meshes or titanium-reinforced membranes with or without collagen membranes in GBR-based VRA, were eligible. Results: A total of 119 patients from three human randomized clinical trials (RCTs) and one case series reported across nine articles were included. The addition of collagen membranes causes no significant differences in vertical bone gain or surgical/healing complication rates. Conclusions: The addition of collagen membranes on top of titanium meshes and titanium-reinforced membranes might not be necessary in GBR-based VRA. Further human RCTs are required to reach a reliable conclusion. Full article
(This article belongs to the Section Dental Biomaterials)
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13 pages, 5559 KiB  
Article
Effects of Different Titanium Anodized Surfaces on Peri-Implant Soft Tissue Healing Around Dental Abutments: In Vitro and Proteomic Study
by Francisco Romero-Gavilán, Andreia Cerqueira, Carlos Arias-Mainer, David Peñarrocha-Oltra, Claudia Salavert-Martínez, Juan Carlos Bernabeu-Mira, Iñaki García-Arnáez, Félix Elortza, Mariló Gurruchaga, Isabel Goñi and Julio Suay
Appl. Sci. 2025, 15(13), 7349; https://doi.org/10.3390/app15137349 - 30 Jun 2025
Viewed by 304
Abstract
Objectives: This study aimed to evaluate the effects of different titanium (Ti) anodized surfaces on soft tissue healing around dental implant abutments. Methods: Discs of machined (MC), pink anodized (PA) and yellow anodized (YA) surfaces were morphologically characterized and evaluated in vitro. Cell [...] Read more.
Objectives: This study aimed to evaluate the effects of different titanium (Ti) anodized surfaces on soft tissue healing around dental implant abutments. Methods: Discs of machined (MC), pink anodized (PA) and yellow anodized (YA) surfaces were morphologically characterized and evaluated in vitro. Cell adhesion and collagen synthesis by human gingival fibroblasts (hGFs) were assessed to evaluate the regenerative potential of the surfaces under study. Their inflammatory potential was evaluated in THP-1 cell cultures by measuring cytokine secretion, and their proteomic adsorption patterns were characterized using nano-liquid chromatography mass spectrometry (nLC-MS/MS). Statistical significance was considered at 5%. In relation to proteomics, statistical differences were evaluated using the Student t-test with the Perseus application. Results: The anodization process resulted in a reduction in the surface roughness parameter (Ra) relative to the machined titanium (p < 0.05). No differences in hGF adhesion were found between the surfaces after one day. PA induced increased hGF collagen synthesis after 7 days (p < 0.05). The secretion of TNF-α was lower for anodized surfaces than for MC, and its concentration was lower for PA than for YA (p < 0.05). In turn, TGF-β was higher for PA and YA versus MC after one and three days of culture. A total of 176 distinct proteins were identified and 26 showed differences in adhesion between the anodized surfaces and MC. These differential proteins were related to coagulation, lipid metabolism, transport activity, plasminogen activation and a reduction in the immune response. Conclusions: Anodized Ti surfaces showed promising anti-inflammatory and regenerative potential for use in dental implant abutments. Anodization reduced surface roughness, increased collagen synthesis and lowered TNF-α secretion while increasing TGF-β levels compared to machined surfaces. Identified proteins related to coagulation and lipid metabolism supported these findings. Clinical relevance: Anodized surfaces could offer improved short-term peri-implant soft tissue healing over machined surfaces. The analysis of abutment surface, instead of implant surface, is a new approach that can provide valuable information. Full article
(This article belongs to the Special Issue Application of Advanced Therapies in Oral Health)
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24 pages, 8054 KiB  
Article
INHIBITION OF THE PROSTAGLANDIN-DEGRADING ENZYME 15-PGDH AMELIORATES MASH-ASSOCIATED APOPTOSIS AND FIBROSIS IN MICE
by Utibe-Abasi S. Udoh, Mathew Steven Schade, Jacqueline A. Sanabria, Pradeep Kumar Rajan, Rodrigo Aguilar, Micheal Andryka, Alexei Gorka, Sandrine V. Pierre and Juan Sanabria
Cells 2025, 14(13), 987; https://doi.org/10.3390/cells14130987 - 27 Jun 2025
Viewed by 1371
Abstract
Background. Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of the world population. Progression to its inflammatory state, MASH, is associated with increasing liver fibrosis, leading to end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC). SW033291, an inhibitor of 15-PGDH [...] Read more.
Background. Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of the world population. Progression to its inflammatory state, MASH, is associated with increasing liver fibrosis, leading to end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC). SW033291, an inhibitor of 15-PGDH (the PGE2 degradation enzyme), has been shown to increase in vivo regeneration of liver parenchyma, ameliorating oxidative stress and inflammation. We hypothesized that SW033291 abrogates MASH progression by inducing a paucity of the initial apoptotic switch and restoring physiological collagen’s microenvironment. Methods. The expression levels of the cell metabolic proteins FOXO1, mTOR, and SIRT7 were determined in a diet-induced MASH-mouse model at 16, 20, and 24 weeks. Non-targeted metabolomics in mouse plasma were measured by LC-MS/MS. Liver morphology and apoptotic activity were quantified by the NAS score and TUNEL assay, respectively. Statistical analyses between groups (NMC, HFD, and SW033291) were determined by ANOVA, t-test/Tukey’s post hoc test using GraphPad Prism. Metabolomics data were analyzed using R-lab. Results. The treated group showed significant decreases in total body fat, cellular oxidative stress, and inflammation and an increase in total lean mass with improved insulin resistance and favorable modulation of metabolic protein expressions (p < 0.05). SW033291 significantly decreased GS:SG, citric acid, and corticosterone, NAS scores (9.4 ± 0.2 vs. 6.2 ± 0.1, p < 0.05), liver fibrosis scores (1.3 ± 0.5 vs. 0.25 ± 0.1, p < 0.05), and apoptotic activity (43.9 ± 4.6 vs. 0.38 ± 0.1%, p < 0.05) compared with controls at 24W. Conclusions. The inhibition of 15-PGDH appears to normalize the metabolic and morphological disturbances during MASH progression with a paucity of the initial apoptotic switch, restoring normal collagen architecture. SW033291 warrants further investigation for its translation. Full article
(This article belongs to the Special Issue Cellular Pathology: Emerging Discoveries and Perspectives in the USA)
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20 pages, 1557 KiB  
Article
The RAGE Inhibitor TTP488 (Azeliragon) Improves Diabetic Bladder Dysfunction in Leptin-Deficient Obese Mice
by Akila Lara Oliveira, Matheus Leite Medeiros, Antonio Thiago Pereira Campos, Carlos Lenz Cesar, Fabiola Zakia Mónica and Edson Antunes
Antioxidants 2025, 14(7), 793; https://doi.org/10.3390/antiox14070793 - 27 Jun 2025
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Abstract
The advanced glycation end product (AGE)–RAGE axis has been implicated in the pathophysiology of diabetic bladder dysfunction (DBD). However, no previous studies have explored the effects of RAGE blockade on this condition. Here, we explored the effects of the selective RAGE inhibitor TTP488 [...] Read more.
The advanced glycation end product (AGE)–RAGE axis has been implicated in the pathophysiology of diabetic bladder dysfunction (DBD). However, no previous studies have explored the effects of RAGE blockade on this condition. Here, we explored the effects of the selective RAGE inhibitor TTP488 (azeliragon) at the functional and molecular levels of bladder dysfunction in ob/ob leptin-deficient mice. Female B6.V-Lep ob/JUnib (ob/ob) and wild-type (WT) C57BL/6 mice were used as lean controls. Treatment with TTP488 in ob/ob mice resulted in no changes in body weight, fasting glucose, or insulin resistance; however, it reduced total AGE and MG-H1 levels without altering RAGE levels in bladder tissues. TTP488 normalized glyoxalase-1, glutathione reductase, glutathione peroxidase, and superoxide dismutase activities in bladder tissues. Marked increases in collagen intensity were also observed in ob/ob mice, an effect fully reversed by TTP488 treatment. TTP488 reduced total void volume, volume per void, and ex vivo bladder contractility in response to electrical-field stimulation and carbachol. Our finding that TTP488 mitigates DBD in ob/ob mice supports the proposal that RAGE blockade could serve as a promising therapeutic strategy for managing DBD. Full article
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