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19 pages, 3231 KB  
Article
Finite Element Analysis of Collared Hip Prosthesis Cross-Sections Under Dynamic Loading and Wear Conditions for Durable Orthopedic Implant Design
by Chethan K N, John Valerian Corda, Laxmikant G. Keni, M. Kalayarasan, Jonathan Reginald and Sudhir Jain Prathik
Prosthesis 2026, 8(4), 36; https://doi.org/10.3390/prosthesis8040036 - 3 Apr 2026
Viewed by 290
Abstract
Background/Objective: Traditional hip implant evaluations often overlook patient-specific dynamic loadings. This study investigates the performance of novel collared hip implant designs under walking conditions, focusing on geometric profiles and two common stem materials: Ti-6Al-4V and CoCr alloy. Methods: Patient-specific dynamic forces were applied [...] Read more.
Background/Objective: Traditional hip implant evaluations often overlook patient-specific dynamic loadings. This study investigates the performance of novel collared hip implant designs under walking conditions, focusing on geometric profiles and two common stem materials: Ti-6Al-4V and CoCr alloy. Methods: Patient-specific dynamic forces were applied using commercial finite element analysis, adhering to ISO and ASTM standards. Four cross-sectional profiles—circular, elliptical, oval, and trapezoidal—were initially evaluated for induced stresses and displacements. Subsequently, wear characteristics at implant junctions were analyzed, comparing CoCr (MC 1) and Ti-6Al-4V (MC 2) stems. The study also assessed the impact of using Ultra-High Molecular Weight Polyethylene (UHMWPE) acetabular cups. Results: The elliptical (CS 2) cross-sectional profile demonstrated superior performance. Junction analysis revealed that the CoCr stem (MC 1) exhibited a stem-to-head sliding distance four times higher and contact pressure 5.5 times higher than the Ti-6Al-4V stem (MC 2). Specifically, MC 1 showed 82% higher contact pressure and 89% greater sliding distance at the stem–head junction compared to MC 2. Additionally, utilizing UHMWPE cups effectively eliminated squeaking sounds attributed to CoCr cups due to superior wear resistance. Conclusions: The combination of an elliptical (CS 2) cross-sectional profile with a Ti-6Al-4V stem and UHMWPE acetabular cup offers optimal performance. This configuration significantly reduces wear and contact pressure, suggesting enhanced functionality and durability for hip implants under dynamic loading conditions. Full article
(This article belongs to the Special Issue Current and Emerging Concepts in Personalized Arthroplasty)
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12 pages, 2264 KB  
Case Report
Branch-Critical Clipping of a Ruptured Carotid–Posterior Communicating Aneurysm with Fetal PCA Configuration
by Catalina-Ioana Tataru, Cosmin Pantu, Alexandru Breazu, Felix-Mircea Brehar, Matei Serban, Razvan-Adrian Covache-Busuioc, Corneliu Toader, Octavian Munteanu, Mugurel Petrinel Radoi and Adrian Vasile Dumitru
Diagnostics 2026, 16(2), 307; https://doi.org/10.3390/diagnostics16020307 - 18 Jan 2026
Viewed by 541
Abstract
Background/Objectives: Aneurysmal subarachnoid hemorrhage (aSAH) involves a sudden onset of a perfusion-pressure injury from the initial insult combined with a secondary injury phase produced by delayed cerebral ischemia, cerebrospinal fluid circulation disturbances, and generalized instability of the patient’s physiological state. The situation may [...] Read more.
Background/Objectives: Aneurysmal subarachnoid hemorrhage (aSAH) involves a sudden onset of a perfusion-pressure injury from the initial insult combined with a secondary injury phase produced by delayed cerebral ischemia, cerebrospinal fluid circulation disturbances, and generalized instability of the patient’s physiological state. The situation may be further complicated when there has been rupture of the aneurysm at the site of the carotid–posterior communicating (PCom) artery junction that occurs in conjunction with a fetal configuration of the posterior cerebral artery (fPCA), thereby making definitive treatment dependent on preserving the critical nature of the branches of the posterior circulation since the aneurysm’s neck plane coincides with the dominant posterior circulation conduit. Case Presentation: A 65-year-old female patient who was obese (Grade III BMI = 42), had chronic bronchial asthma, and arterial hypertension experienced a “thunderclap” type of headache in the right retro-orbital area followed by a syncopal episode and developed acute confusion with agitation. Upon admission to the hospital, her Glasgow Coma Scale (GCS) was 13, her FOUR score was 15, her Montreal Cognitive Assessment (MoCA) score was 12/30, her Hunt–Hess grade was 3, WFNS grade 2, and Fisher grade 4 SAH with intraventricular extension. Digital subtraction angiography (DSA) and three-dimensional rotational angiography revealed a posteriorly directed right carotid communicating aneurysm that had a relatively compact neck (approximately 2.5 mm) and sac size of approximately 7.7 × 6.6 mm, with the fPCA originating at the neck plane. Microsurgical treatment was performed with junction-preserving reconstruction with skull base refinement, temporary occlusion of the internal carotid artery for a few minutes, placement of clips reconstructing the carotid–PCom interface, and micro-Doppler verification of patent vessel. Postoperatively, the blood pressure was kept within the range of 110–130 mmHg with nimodipine and closely monitored. The neurological recovery was sequential (GCS of 15 by POD 2; MoCA of 22 by POD 5). By POD 5 CT scan, the clip remained positioned in a stable fashion without evidence of infarct, hemorrhage, or hydrocephalus; at three months she was neurologically intact (mRS 0; Barthel 100; MoCA 28/30), and CTA confirmed persistent exclusion of the aneurysm and preservation of fPCA flow. Conclusions: In cases where the ruptured aneurysm is located at the carotid communicating junction with the PCom artery in a configuration of the posterior cerebral artery that is described as fetal, clip treatment should be viewed as a form of branch-preserving junction reconstruction of the carotid–PCom junction supported by adherence to controlled postoperative physiology and close ppostoperativesurveillance. Full article
(This article belongs to the Special Issue Advances in Diagnostic Imaging for Cerebrovascular Diseases)
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17 pages, 3407 KB  
Case Report
An Anatomy-Guided, Stepwise Microsurgical Reconstruction of a Posteriorly Projecting ICA–PCoA Aneurysm Beneath the Optic Apparatus: A Detailed Operative Sequence
by Matei Șerban, Corneliu Toader and Răzvan-Adrian Covache-Busuioc
Diagnostics 2026, 16(1), 124; https://doi.org/10.3390/diagnostics16010124 - 1 Jan 2026
Viewed by 596
Abstract
Background: Posteriorly directed aneurysms at the internal carotid–posterior communicating artery (ICA–PCoA) junction concentrate technical risk at the posteromedial neck where the PCoA origin and perforators exist beneath the optic apparatus. Our aim was to describe, in a reproducible fashion, an anatomy-driven sequence [...] Read more.
Background: Posteriorly directed aneurysms at the internal carotid–posterior communicating artery (ICA–PCoA) junction concentrate technical risk at the posteromedial neck where the PCoA origin and perforators exist beneath the optic apparatus. Our aim was to describe, in a reproducible fashion, an anatomy-driven sequence in the management of a ruptured ICA–PCoA aneurysm that visualized the posterior wall and a closing line parallel to the PCoA axis and which is placed within contemporary practice. Case Presentation: This is a single case study employing predetermined surgical techniques demonstrating a reproducible method of anatomical microsurgery applied to a posterior projecting ICA-PCoA aneurysm. The authors describe a 62-year-old female who was stabilized by nimodipine and aggressive blood pressure control in the systolic range 140–160 mmHg after an aneurysmal subarachnoid hemorrhage. Diagnostic contrast catheter angiography showed a left ICA-PCoA aneurysm of 13.1 × 10.0 mm at the base with a neck of 4.3 mm projecting posteriorly into the carotid–optic cistern. Complete adherence to a protocol of staged techniques was employed for the operation, as detailed below. Step 1: Early cisternal decompression requiring total and immediate relaxation of the temporal lobe, rapidly opening up the carotid–optic anatomical window. Step 2: Circumferential dissection about the neck of the aneurysm permitting definition of the true posteromedial wall and definition of the perforator territories and anterior choroidal territories. Step 3: Brief but effective ICA proximal quiescence (58 s) permitting clipping under direct vision. Step 4: Staged closure of two clips with the closing line of the clips orientated parallel to the axis of the PCoA with maintenance of the diameter of all parent vessels, the origin of the PCoA and the integrity of the perforators. Urgent postoperative digital subtraction angiography (DSA) study showed complete exclusion of the aneurysm with no alteration in flow characteristics, and 3 months later DSA studies again showed permanent obliteration and patency of those branches. The immediate DSA demonstrated complete exclusion of the aneurysm with patent supraclinoid ICA caliber and PCoA ostium, the anterior choroidal artery was preserved; no angiographic vasospasm was identified. The postoperative course was uncomplicated; there was no hydrocephalus, seizure disorder or delayed ischemia. At discharge and three months postprocedure the patient was neurologically intact (Modified Rankin Scale 0). Non-contrast cranial CT (three months) demonstrated stable clip position and no hemorrhagic or ischemic sequelae. Conclusions: In posteriorly projecting ICA–PCoA aneurysms that are disturbed beneath the optic apparatus, an anatomy-guided strategy—early cisternal decompression, true posteromedial neck exposure, brief purposeful quieting of the proximal ICA and two-clip closure parallel to the PCoA in selected cases—may provide the opportunity for durable occlusion whilst the physiology of branching is preserved. We intend for this transparent description to be adopted, refined or discarded based on local anatomy and practice. Full article
(This article belongs to the Special Issue Cerebrovascular Lesions: Diagnosis and Management, 2nd Edition)
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24 pages, 721 KB  
Review
Fusobacteriumnucleatum: Pathophysiological and Clinical Involvement in Inflammatory Bowel Diseases, Colorectal Cancer and Cardiovascular Diseases
by Vincenzo Quagliariello, Pietro Forte, Giuliana Ciappina, Luigi Colarusso, Carlotta Giorgi, Francesco Fiorica, Antonio Bottari, Giordana Di Mauro, Nicola Maurea and Massimiliano Berretta
Cancers 2025, 17(20), 3348; https://doi.org/10.3390/cancers17203348 - 17 Oct 2025
Cited by 1 | Viewed by 2526
Abstract
Fusobacterium nucleatum is a Gram-negative anaerobe that occupies a central ecological niche in oral biofilms but has emerged as a trans-compartmental pathogen implicated in gastrointestinal and cardiovascular diseases. In inflammatory bowel diseases, Fusobacterium nucleatum adheres to the intestinal epithelium via adhesins such as [...] Read more.
Fusobacterium nucleatum is a Gram-negative anaerobe that occupies a central ecological niche in oral biofilms but has emerged as a trans-compartmental pathogen implicated in gastrointestinal and cardiovascular diseases. In inflammatory bowel diseases, Fusobacterium nucleatum adheres to the intestinal epithelium via adhesins such as FadA, disrupts tight junctions, and induces Toll-like receptor–mediated inflammatory cascades, amplifying epithelial permeability and sustaining mucosal inflammation. In colorectal cancer, Fusobacterium nucleatum promotes carcinogenesis through multiple mechanisms, including β-catenin activation, modulation of oncogenic microRNAs, and immune evasion via Fap2–TIGIT signaling, while also fostering a pro-inflammatory and immunosuppressive tumor microenvironment. Its enrichment correlates with advanced tumor stage, chemoresistance, and poor prognosis, underscoring its potential as a biomarker and therapeutic target. Beyond the gut, Fusobacterium nucleatum has been detected in atherosclerotic plaques and endocardial tissues, where it contributes to endothelial dysfunction, foam cell formation, oxidative stress, and plaque instability, thereby linking chronic oral infection with cardiovascular risk. Collectively, evidence suggests that Fusobacterium nucleatum acts as a pathophysiological connector across IBD, CRC, and CVD through conserved mechanisms of adhesion, immune modulation, and inflammation. Understanding these processes provides opportunities for innovative interventions, ranging from targeted antimicrobials and host-directed therapies to dietary and microbiome-based strategies, aimed at mitigating the systemic burden of this organism and improving clinical outcomes across multiple diseases. Full article
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18 pages, 1458 KB  
Article
Type 2 Diabetes Mellitus Impairs the Reverse Transendothelial Migration Capacity (rTEM) of Inflammatory CD14+CD16 Monocytes: Novel Mechanism for Enhanced Subendothelial Monocyte Accumulation in Diabetes
by Dilvin Semo, Adama Sidibé, Kallipatti Sanjith Shanmuganathan, Nicolle Müller, Ulrich A. Müller, Beat A. Imhof, Rinesh Godfrey and Johannes Waltenberger
Cells 2025, 14(19), 1567; https://doi.org/10.3390/cells14191567 - 9 Oct 2025
Cited by 1 | Viewed by 1216
Abstract
Background: Type 2 diabetes mellitus (DM) is a major cardiovascular risk factor that induces monocyte dysfunction and contributes to their accumulation in atherosclerotic lesions. Monocyte recruitment and accumulation in the tissues contribute to chronic inflammation and are essential to the pathobiology of diabetes-induced [...] Read more.
Background: Type 2 diabetes mellitus (DM) is a major cardiovascular risk factor that induces monocyte dysfunction and contributes to their accumulation in atherosclerotic lesions. Monocyte recruitment and accumulation in the tissues contribute to chronic inflammation and are essential to the pathobiology of diabetes-induced atherosclerosis. However, the mechanisms that drive the accumulation of monocytes in the diabetic environment are not clearly understood. Methods: Primary monocytes from type 2 (T2) DM and non-T2DM individuals were isolated using magnet-assisted cell sorting. To examine the influence of a diabetic milieu on monocyte function, monocytes from T2DM patients, db/db mice, or human monocytes subjected to hyperglycaemia were analysed for their responses to pro-atherogenic cytokines using Boyden chamber assays. Furthermore, the interactions of non-diabetic and diabetic monocytes with TNFα-inflamed endothelium were studied using live-cell imaging under physiological flow conditions. RT-qPCR and FACS were used to study the expression of relevant molecules involved in monocyte-endothelium interaction. Results: CD14+CD16 monocytes isolated from T2DM patients or monocytes exposed to hyperglycaemic conditions showed reduced chemotactic responses towards atherosclerosis-promoting cytokines, CCL2 and CX3CL1, indicating monocyte dysfunction. Under flow conditions, the transendothelial migration (TEM) capacity of T2DM monocytes was significantly reduced. Even though these monocytes adhered to the endothelial monolayer, only a few transmigrated. Interestingly, the T2DM monocytes and monocytes exposed to hyperglycaemic conditions accumulated in the ablumen following transendothelial migration. The time period in the ablumen of T2DM cells was prolonged, as there was a significant impairment of the reverse transendothelial migration (rTEM). Mechanistically, the T2DM milieu specifically induced the activation of monocyte integrins, Macrophage-1 antigen (Mac-1; integrin αMβ2 consisting of CD11b and CD18), and Lymphocyte function-associated antigen 1 (LFA-1; αLβ2 consisting of CD11a and CD18). Furthermore, elevated levels of CD18 transcripts were detected in T2DM monocytes. Junctional Adhesion Molecule 3 (JAM-3)–MAC-1 interactions are known to impede rTEM and T2DM milieu-potentiated JAM-3 expression in human coronary artery endothelial cells (HCAEC). Finally, the overexpression of JAM-3 on HCAEC was sufficient to completely recapitulate the impaired rTEM phenotype. Conclusions: Our results revealed for the first time that the enhanced T2DM monocyte accumulation in the ablumen is not secondary to the elevated transmigration through the endothelium. Instead, the accumulation of monocytes is due to the direct consequence of a dysfunctional rTEM, potentially due to enhanced JAM3-MAC1 engagement. Our results highlight the importance of restoring the rTEM capacity of monocytes to reduce monocyte accumulation-dependent inflammation induction and atherogenesis in the T2DM environment. Full article
(This article belongs to the Special Issue Novel Insight into Endothelial Function and Atherosclerosis)
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20 pages, 1831 KB  
Article
Saccharomyces boulardii CNCM I-745 Supernatant Improves Markers of Gut Barrier Function and Inflammatory Response in Small Intestinal Organoids
by Louisa Filipe Rosa, Steffen Gonda, Nadine Roese and Stephan C. Bischoff
Pharmaceuticals 2025, 18(8), 1167; https://doi.org/10.3390/ph18081167 - 6 Aug 2025
Viewed by 5853
Abstract
Objectives: Saccharomyces boulardii CNCM I-745, a probiotic yeast, is effectively used for the treatment of acute diarrhea as well as for the prevention and treatment of traveller‘s diarrhea and diarrhea under tube feeding. The underlying mechanisms are not fully elucidated. Both antitoxic [...] Read more.
Objectives: Saccharomyces boulardii CNCM I-745, a probiotic yeast, is effectively used for the treatment of acute diarrhea as well as for the prevention and treatment of traveller‘s diarrhea and diarrhea under tube feeding. The underlying mechanisms are not fully elucidated. Both antitoxic and regulatory effects on the intestinal barrier, mediated either by the yeast or yeast-derived substrates, have been discussed. Methods: To examine the effects of Saccharomyces boulardii released substrates (S.b.S) on gastrointestinal (GI) barrier function, a murine small intestinal organoid cell model under stress was used. Stress was induced by lipopolysaccharide (LPS) exposure or withdrawal of growth factors from cell culture medium (GFRed). Stressed organoids were treated with S.b.S (200 µg/mL), and markers of GI barrier and inflammatory response were assessed. Results: GFRed-induced stress was characterized by disturbances in selected tight junction (TJ) (p < 0.05), adherent junction (AJ) (p < 0.001), and mucin (Muc) formation (p < 0.01), measured by gene expressions, whereby additional S.b.S treatment was found to reverse these effects by increasing Muc2 (from 0.22 to 0.97-fold change, p < 0.05), Occludin (Ocln) (from 0.37 to 3.5-fold change, p < 0.0001), and Claudin (Cldn)7 expression (from 0.13 ± 0.066-fold change, p < 0.05) and by decreasing Muc1, Cldn2, Cldn5, and junctional adhesion molecule A (JAM-A) expression (all p < 0.01). Further, S.b.S normalized expression of nucleotide binding oligomerization domain (Nod)2- (from 44.5 to 0.51, p < 0.0001) and matrix metalloproteinase (Mmp)7-dependent activation (from 28.3 to 0.02875 ± 0.0044 ** p < 0.01) of antimicrobial peptide defense and reduced the expression of several inflammatory markers, such as myeloid differentiation primary response 88 (Myd88) (p < 0.01), tumor necrosis factor α (Tnfα) (p < 0.01), interleukin (IL)-6 (p < 0.01), and IL-1β (p < 0.001). Conclusions: Our data provide new insights into the molecular mechanisms by which Saccharomyces boulardii CNCM I-745-derived secretome attenuates inflammatory responses and restores GI barrier function in small intestinal organoids. Full article
(This article belongs to the Topic Probiotics: New Avenues)
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13 pages, 7555 KB  
Article
Healed Perforated Corneal Ulcers in Human
by Yasser Helmy Mohamed, Masafumi Uematsu, Mao Kusano, Keiji Suzuki and Akio Oishi
Life 2025, 15(6), 939; https://doi.org/10.3390/life15060939 - 11 Jun 2025
Viewed by 1122
Abstract
This study investigates the pathophysiological process of healed perforated corneal ulcers (HPCUs) in humans. All subjects underwent keratoplasty due to opacities or leakage from HPCUs. Half of each specimen was fixed with 4% glutaraldehyde for transmission electron microscope (TEM) examination. The other half [...] Read more.
This study investigates the pathophysiological process of healed perforated corneal ulcers (HPCUs) in humans. All subjects underwent keratoplasty due to opacities or leakage from HPCUs. Half of each specimen was fixed with 4% glutaraldehyde for transmission electron microscope (TEM) examination. The other half was fixed in 10% formaldehyde for immunofluorescence (IF) examination. TEM identified layered structures with two cell types (polygonal and elongated) connected by gap or adherent junctions during early stage of healing. Both apoptotic and mitotic changes were found in both types of cells. There were no endothelial cells or Descemet’s membrane (DM) present in early stage of healing. During the intermediate stage, the healed area comprised three layers: epithelium, Bowman’s layer, and stroma, with an increase in stromal collagen. Later, adjacent endothelial cells crept in, forming DM and completing the cornea’s 5-layer structure. IF examinations revealed that vimentin+ and α-smooth muscle actin (αSMA)+ myofibroblasts gathered around the damaged site. Proliferating cell nuclear antigen+ cells, which indicated cell proliferation, were found in both cells. Anti-phospho-histone H2AX antibodies were found in some epithelial cells. CK14-positive cells were only found in superficial polygonal cells. Corneal wound healing is a complex process that includes apoptosis, cell migration, mitosis, differentiation, and extracellular matrix remodeling. Full article
(This article belongs to the Special Issue Feature Paper in Physiology and Pathology: 2nd Edition)
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19 pages, 3466 KB  
Article
Tannic Acid and Ethacridine Lactate Attenuate Markers of Stress-Induced Intestinal Barrier Dysfunctions in Murine Small Intestinal Organoids
by Louisa Filipe Rosa, Steffen Gonda, Nadine Roese and Stephan C. Bischoff
Biomolecules 2025, 15(5), 650; https://doi.org/10.3390/biom15050650 - 30 Apr 2025
Cited by 4 | Viewed by 1752
Abstract
(1) Background: Tannacomp® is a drug consisting of tannin albuminate, a complex of tannic acid (TA) and ethacridine lactate (Eta) used for treating acute and traveler’s diarrhea. TA is thought to modulate gastrointestinal barrier function, but the underlying mechanisms and whether Eta [...] Read more.
(1) Background: Tannacomp® is a drug consisting of tannin albuminate, a complex of tannic acid (TA) and ethacridine lactate (Eta) used for treating acute and traveler’s diarrhea. TA is thought to modulate gastrointestinal barrier function, but the underlying mechanisms and whether Eta has similar effects remains unclear. (2) Methods: to investigate the effects of TA and Eta on the intestinal barrier, stress responses were induced in murine intestinal organoids by lipopolysaccharide (LPS) exposure or withdrawal of growth factors from cell culture medium (GFRed). Further, organoids were exposed to either TA (0.01 mg/mL) or Eta (0.002 mg/mL) and markers of inflammatory response and gut barrier function were assessed. (3) Results: TA and Eta reduced several inflammatory markers such as interleukin 6, interleukin 1β, tumor necrosis factor α, and myeloid differentiation primary response 88 in stressed organoids. In addition, TA and Eta attenuated LPS- and GFRed-mediated gut barrier dysfunctions, with normalization of tight junction, adherent junction and mucin gene expression and reduction of Nod2- and matrix metalloproteinase 7-dependent activation of antimicrobial peptides. (4) Conclusions: our data show that TA and Eta modulate markers of inflammation and the intestinal barrier and suggest novel mechanisms of action of this drug that could broaden its treatment indications. Full article
(This article belongs to the Section Molecular Medicine)
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22 pages, 14156 KB  
Article
Plasticity of Expression of Stem Cell and EMT Markers in Breast Cancer Cells in 2D and 3D Culture Depend on the Spatial Parameters of Cell Growth; Mathematical Modeling of Mechanical Stress in Cell Culture in Relation to ECM Stiffness
by Małgorzata Szostakowska-Rodzoś, Mateusz Chmielarczyk, Weronika Zacharska, Anna Fabisiewicz, Agata Kurzyk, Izabella Myśliwy, Zofia Kozaryna, Eligiusz Postek and Ewa A. Grzybowska
Bioengineering 2025, 12(2), 147; https://doi.org/10.3390/bioengineering12020147 - 4 Feb 2025
Cited by 3 | Viewed by 2675
Abstract
The majority of the current cancer research is based on two-dimensional cell cultures and animal models. These methods have limitations, including different expressions of key factors involved in carcinogenesis and metastasis, depending on culture conditions. Addressing these differences is crucial in obtaining physiologically [...] Read more.
The majority of the current cancer research is based on two-dimensional cell cultures and animal models. These methods have limitations, including different expressions of key factors involved in carcinogenesis and metastasis, depending on culture conditions. Addressing these differences is crucial in obtaining physiologically relevant models. In this manuscript we analyzed the plasticity of the expression of stem cell and epithelial/mesenchymal markers in breast cancer cells, depending on culture conditions. Significant differences in marker expression were observed in different growth models not only between 2D and 3D conditions but also between two different 3D models. Differences observed in the levels of adherent junction protein E-cadherin in two different 3D models suggest that spatial parameters of cell growth and physical stress in the culture may affect the expression of junction proteins. To provide an explanation of this phenomenon on the grounds of mechanobiology, these parameters were analyzed using a mathematical model of the 3D bioprinted cell culture. The finite element mechanical model generated in this study includes an extracellular matrix and a group of regularly placed cells. The single-cell model comprises an idealized cytoskeleton, cortex, cytoplasm, and nucleus. The analysis of the model revealed that the stress generated by external pressure is transferred between the cells, generating specific stress fields, depending on growth conditions. We have analyzed and compared stress fields in two different growth conditions, each corresponding to a different elasticity of extracellular matrix. We have demonstrated that soft matrix conditions produce more stress than a stiff matrix in the single cell as well as in cellular spheroids. The observed differences can explain the plasticity of E-cadherin expression in response to mechanical stress. These results should contribute to a better understanding of the differences between various growth models. Full article
(This article belongs to the Special Issue Mathematical and Computational Modeling of Cancer Progression)
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25 pages, 5099 KB  
Article
Pathophysiological Responses of Oral Keratinocytes After Exposure to Flavored E-Cigarette Liquids
by Abrar Shamim, Hannah Herzog, Raivat Shah, Sara Pecorelli, Virginia Nisbet, Ann George, Giancarlo A. Cuadra and Dominic L. Palazzolo
Dent. J. 2025, 13(2), 60; https://doi.org/10.3390/dj13020060 - 29 Jan 2025
Cited by 3 | Viewed by 3247
Abstract
Background: Electronic cigarettes (ECIGs) have grown in popularity, particularly among adolescents and young adults. Flavored ECIG-liquids (E-liquids) are aerosolized by these ECIGs and inhaled into the respiratory system. Several studies have shown detrimental effects of E-liquids in airway tissues, revealing that flavoring agents [...] Read more.
Background: Electronic cigarettes (ECIGs) have grown in popularity, particularly among adolescents and young adults. Flavored ECIG-liquids (E-liquids) are aerosolized by these ECIGs and inhaled into the respiratory system. Several studies have shown detrimental effects of E-liquids in airway tissues, revealing that flavoring agents may be the most irritating component. However, research on the effects of E-liquids on biological processes of the oral cavity, which is the first site of aerosol contact, is limited. Hence, this study focuses on the effects of E-liquid flavors on oral epithelial cells using the OKF6/TERT-2 cell line model. Methodology: E-liquid was prepared with and without flavors (tobacco, menthol, cinnamon, and strawberry). OKF6/TERT-2 oral epithelial cells, cultured at 37 °C and 5% CO2, were exposed to 1% E-liquid ± flavors for 24 h. Outcomes determined include cell morphology, media pH, wound healing capability, oxidative stress, expression of mucin and tight junction genes, glycoprotein release, and levels of inflammatory cytokines (TNFα, IL-6, and IL-8). Results: Exposure to 1% flavored E-liquids negatively affect cellular confluency, adherence, and morphology. E-liquids ± flavors, particularly cinnamon, increase oxidative stress and production of IL-8, curtail wound healing recovery, and decrease glycoprotein release. Gene expression of muc5b is downregulated after exposure to E-liquids. In contrast, E-liquids upregulate occludin and claudin-1. Conclusions: This study suggests that ECIG use is not without risk. Flavored E-liquids, particularly cinnamon, result in pathophysiological responses of OKF6/TERT-2 cells. The dysregulation of inflammatory responses and cellular biology induced by E-liquids may contribute to various oral pathologies. Full article
(This article belongs to the Special Issue Dentistry in the 21st Century: Challenges and Opportunities)
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13 pages, 2143 KB  
Review
Crown Lengthening Surgery in the Esthetic Area for Optimized Results: A Review with Surgical Recommendations
by Sérgio Kahn, Walmir Júnio de Pinho Reis Rodrigues, Alexandra Tavares Dias, Rodrigo Resende, Juliana Campos Hasse Fernandes and Gustavo Vicentis Oliveira Fernandes
Surgeries 2024, 5(4), 1043-1055; https://doi.org/10.3390/surgeries5040084 - 28 Nov 2024
Cited by 7 | Viewed by 8099
Abstract
Background: Crown lengthening (CL) in esthetic areas has become a versatile procedure with applications in many clinical situations. Knowledge concerning different periodontal phenotypes, and the supracrestal tissue attachment (STA)—former biological width—has allowed for a better understanding of surgical management, allowing for the individualization [...] Read more.
Background: Crown lengthening (CL) in esthetic areas has become a versatile procedure with applications in many clinical situations. Knowledge concerning different periodontal phenotypes, and the supracrestal tissue attachment (STA)—former biological width—has allowed for a better understanding of surgical management, allowing for the individualization of surgical therapy. This review presented an individualized surgical approach to CL in esthetic areas based on evaluating the phenotype and current considerations about the STA, correlating them to suggestive surgical techniques. Methods: For an individualized surgical approach, it is primarily necessary to understand STA, including the relationship and distance between the cementoenamel junction (CEJ) and the bone crest (BC) and the position of the free gingival margin (FGM); secondarily, it is necessary to verify the periodontal phenotype to prepare surgical planning (gingivectomy or osseous resection/contouring). Three periodontal phenotypes are recognized, presenting different biological behaviors due to specific characteristics implicitly correlated to soft tissue management. Results: Then, after assessing the distance from the CEJ to the BC, the position of the FGM, and the periodontal phenotype, it is possible to individualize the treatment according to the phenotype. In cases of a thin and scalloped periodontium with delicate gingiva, there might be the presence of bone dehiscence, fenestration, and instability in the healing of the gingival margin, bringing extra attention to tissue manipulation and suggesting a minimally invasive technique (no flap). A partial-thickness flap is recommended for a thick and scalloped periodontium, keeping the periosteum adhered to the bone. For periodontium B (fibrous and dense gingiva and tissue resistant to injuries), the surgical approach recommended is an open full-thickness flap with osteotomy for horizontal and vertical bone volume removal. Then, observing first the specific parameters, such as the STA, CEJ, BC, FGM, and KTW, and then the characteristics of periodontal phenotypes, it is possible to determine the individualized surgical strategy and a reasonable surgical approach to tissue manipulation in clinical CL surgeries. Conclusions: The surgical approach must be defined according to individualized planning since several variables can influence the dynamics of the periodontal tissues. Full article
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31 pages, 8437 KB  
Article
Multifunctional Ag-Poly(N-isopropylacrylamide/itaconic Acid) Hydrogel Nanocomposites Prepared by Gamma Irradiation for Potential Application as Topical Treatment Dressings
by Jelena Spasojević, Milica Milošević, Sašenka Vidičević-Novaković, Jelena Tasić, Petar Milovanović, Marija Djurić, Dragan Ranković, Zorica Kačarević-Popović and Aleksandra Radosavljević
Polymers 2024, 16(22), 3211; https://doi.org/10.3390/polym16223211 - 19 Nov 2024
Cited by 4 | Viewed by 2324
Abstract
Today, hydrogel dressings that can protect injury sites and effectively promote healing have become highly desirable in wound management. Therefore, multifunctional silver-poli(N-isopropylacrylamide/itaconic acid) (Ag-P(NiPAAm/IA)) hydrogel nanocomposites were developed for potential application as topical treatment dressings. The radiolytic method, used for the [...] Read more.
Today, hydrogel dressings that can protect injury sites and effectively promote healing have become highly desirable in wound management. Therefore, multifunctional silver-poli(N-isopropylacrylamide/itaconic acid) (Ag-P(NiPAAm/IA)) hydrogel nanocomposites were developed for potential application as topical treatment dressings. The radiolytic method, used for the crosslinking of the polymer matrix as well as for the in situ incorporation of silver nanoparticles (AgNPs) into the polymer matrix, enables the preparation of hydrogel nanocomposites without introducing harmful and toxic agents. Moreover, materials produced using γ-irradiation are simultaneously sterilized, thus fulfilling one of the basic requirements regarding their potential biomedical applications. The NiPAAm/IA ratio and the presence of AgNPs influenced the microstructural parameters of the investigated systems. Increasing the IA content leads to the formation of a more porous polymer matrix with larger pores, while the incorporated AgNPs act as additional junction points, decreasing the porosity and pore size of the resulting nanocomposite hydrogels. Swelling studies showed that most investigated systems uptake the fluids from their surroundings by non-Fick diffusion. Further, the Ag+ ion release, antibacterial activity, and cytotoxicity of Ag-P(NiPAAm/IA) hydrogel nanocomposites were examined to evaluate their biomedical potential. All hydrogel nanocomposites showed an initial burst release of Ag+ ions (useful in preventing bacteria adherence and biofilm formation), followed by a slower release of the same (ensuring sterility for longer use). An antibacterial activity test against Escherichia coli and Staphylococcus aureus showed that Ag-P(NiPAAm/IA) hydrogel nanocomposites, with silver concentrations around 10 ± 1 ppm, successfully prevent bacterial growth. Finally, it was shown that the investigated hydrogel nanocomposites do not exhibit a cytotoxic effect on human keratinocyte HaCaT cells. Therefore, these multifunctional hydrogel nanocomposites may promote wound repair and show promising potential for application as functional wound dressing. Full article
(This article belongs to the Special Issue Polymer Hydrogels: Synthesis, Properties and Applications)
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17 pages, 8799 KB  
Article
The Therapeutic Effects of Lactic Acid Bacteria Isolated from Spotted Hyena on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice
by Mengen Xu, Miao Hu, Jingbo Han, Lei Wang, Yuanyuan He, Md. F. Kulyar, Xiaohu Zhang, Yaozhong Lu, Siyang Mu, Hang Su, Jintao Cao and Jiakui Li
Nutrients 2024, 16(21), 3682; https://doi.org/10.3390/nu16213682 - 29 Oct 2024
Cited by 4 | Viewed by 2251
Abstract
Background: Inflammatory bowel disease (IBD) is a chronic condition characterized by recurrent episodes and an unclear etiology. Given the limitations of current therapeutic options, which include suboptimal efficacy and significant side effects, there is a pressing need to explore novel treatments. Probiotics derived [...] Read more.
Background: Inflammatory bowel disease (IBD) is a chronic condition characterized by recurrent episodes and an unclear etiology. Given the limitations of current therapeutic options, which include suboptimal efficacy and significant side effects, there is a pressing need to explore novel treatments. Probiotics derived from diverse species have been identified as a promising approach for managing IBD, owing to their anti-inflammatory properties and their ability to regulate gut flora, among other beneficial effects. Methods: In this study, three strains of lactic acid bacteria (LAB) were isolated from the feces of the scavenger spotted hyena (Crocuta crocuta), a scavenging mammal. Based on their capability to survive within and adhere to the gastrointestinal tract, along with their profile of antibiotic resistance, a high-quality strain of Lactobacillus acidophilus (LA) was selected and demonstrated to be safe for mice. Subsequently, the therapeutic efficacy of LA was evaluated using a dextran sulfate sodium (DSS)-induced model of ulcerative colitis in mice. Results: The results indicated that LA restored the disease activity index and improved histopathological lesions in the model group. It also reduced inflammation and oxidative stress and significantly restored the expression of mucins and intestinal tight junction (TJ) proteins (ZO-1, Occludin). Furthermore, LA corrected the DSS-induced disruption of the intestinal flora, leading to a significant decrease in the prevalence of potentially harmful bacterial genera, such as Bacteroides, and an increase in beneficial bacterial genera, including Lactobacillus. In conclusion, Lactobacillus acidophilus LA1, isolated from spotted hyena feces, has potential as a functional supplement for alleviating symptoms of IBD and regulating intestinal flora. Full article
(This article belongs to the Section Prebiotics, Probiotics and Postbiotics)
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34 pages, 15743 KB  
Article
Catching the Big Fish in Big Data: A Meta-Analysis of Zebrafish Kidney scRNA-Seq Datasets Highlights Conserved Molecular Profiles of Macrophages and Neutrophils in Vertebrates
by Aleksandr V. Bobrovskikh, Ulyana S. Zubairova, Ludmila G. Naumenko and Alexey V. Doroshkov
Biology 2024, 13(10), 773; https://doi.org/10.3390/biology13100773 - 27 Sep 2024
Cited by 5 | Viewed by 4784
Abstract
The innate immune system (IIS) is an ancient and essential defense mechanism that protects animals against a wide range of pathogens and diseases. Although extensively studied in mammals, our understanding of the IIS in other taxa remains limited. The zebrafish (Danio rerio [...] Read more.
The innate immune system (IIS) is an ancient and essential defense mechanism that protects animals against a wide range of pathogens and diseases. Although extensively studied in mammals, our understanding of the IIS in other taxa remains limited. The zebrafish (Danio rerio) serves as a promising model organism for investigating IIS-related processes, yet the immunogenetics of fish are not fully elucidated. To address this gap, we conducted a meta-analysis of single-cell RNA sequencing (scRNA-seq) datasets from zebrafish kidney marrow, encompassing approximately 250,000 immune cells. Our analysis confirms the presence of key genetic pathways in zebrafish innate immune cells that are similar to those identified in mammals. Zebrafish macrophages specifically express genes encoding cathepsins, major histocompatibility complex class II proteins, integral membrane proteins, and the V-ATPase complex and demonstrate the enrichment of oxidative phosphorylation ferroptosis processes. Neutrophils are characterized by the significant expression of genes encoding actins, cytoskeleton organizing proteins, the Arp2/3 complex, and glycolysis enzymes and have demonstrated their involvement in GnRH and CLR signaling pathways, adherents, and tight junctions. Both macrophages and neutrophils highly express genes of NOD-like receptors, phagosomes, and lysosome pathways and genes involved in apoptosis. Our findings reinforce the idea about the existence of a wide spectrum of immune cell phenotypes in fish since we found only a small number of cells with clear pro- or anti-inflammatory signatures. Full article
(This article belongs to the Special Issue Immune Response Regulation in Animals)
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20 pages, 2075 KB  
Systematic Review
Tumor-Like Lesions in the Craniovertebral Junction: A Case Series, Systematic Review, and Meta-Analysis
by Maria Mihaela Pop, Dragos Bouros, Artsiom Klimko, Laura Ancuta Pop, Paula Topal, Anil Topal and Ioan Stefan Florian
Cancers 2024, 16(16), 2788; https://doi.org/10.3390/cancers16162788 - 7 Aug 2024
Cited by 3 | Viewed by 3761
Abstract
Background: Tumor-like lesions at the craniovertebral junction mimic tumors in clinical presentation and imaging. Our study focuses on three common developmental pathologies—epidermoids, dermoids and neurenteric cysts. Methods: We conducted a retrospective analysis of a case series and a meta-analysis of 170 [...] Read more.
Background: Tumor-like lesions at the craniovertebral junction mimic tumors in clinical presentation and imaging. Our study focuses on three common developmental pathologies—epidermoids, dermoids and neurenteric cysts. Methods: We conducted a retrospective analysis of a case series and a meta-analysis of 170 patients from 119 reports. Results: Neurenteric cysts predominated (81.2%). Anterior cysts were linked to neurenteric cysts, while posterior ones correlated with dermoid/epidermoid cysts (p < 0.001). Complications occurred in 27.2% of cases, with cranial nerve paresis being the most common. Most patients had excellent outcomes (75.2%) with low recurrence rates (12%). Dermoid cysts were more associated with anomalies (p < 0.001). Among 138 neurenteric cyst cases, 15 experienced recurrence, with predictors including ages 51–60 and over 70, subtotal resection, complications, and poor outcomes (p < 0.001). Cysts with total resection were significantly less likely to adhere to surrounding brain tissue (p < 0.001). CSF diversion was correlated with older age (p = 0.010) and various complications (p < 0.001). Age affected outcomes, and the hydrocephalus was linked to poor outcomes (p = 0.002). Conclusions: This meta-analysis underscores the importance of total resection in minimizing recurrence rates and emphasizes meticulous preoperative planning and imaging. Our results indicate that rim enhancement (p = 0.047) and poor outcome (p = 0.007) are significant factors associated with recurrence. Additionally, associated anomalies, as well as the patient’s age and overall health, significantly influence the surgical outcomes and the likelihood of recurrence. Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
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