Search Results (219)

Congenital spinal deformities (CSDs) are rare but severe conditions caused by abnormalities in vertebral development during embryogenesis. These deformities, including scoliosis, kyphosis, and lordosis, significantly impair patients’ quality of life and present challenges in diagnosis and treatment. This review integrates genetic, molecular, and developmental insights to provide a comprehensive framework for classifying and understanding CSDs. Traditional classification systems based on morphological criteria, such as failures in vertebral formation, segmentation, or mixed defects, are evaluated alongside newer molecular-genetic approaches. Advances in genetic technologies, including whole-exome sequencing, have identified critical genes and pathways involved in somitogenesis and sclerotome differentiation, such as TBX6, DLL3, and PAX1, as well as key signaling pathways like Wnt, Notch, Hedgehog, BMP, and TGF-β. These pathways regulate vertebral development, and their disruption leads to skeletal abnormalities. The review highlights the potential of molecular classifications based on genetic mutations and developmental stage-specific defects to enhance diagnostic precision and therapeutic strategies. Early diagnosis using non-invasive prenatal testing (NIPT) and emerging tools like CRISPR-Cas9 gene editing offer promising but ethically complex avenues for intervention. Limitations in current classifications and the need for further research into epigenetic and environmental factors are discussed. This study underscores the importance of integrating molecular genetics into clinical practice to improve outcomes for patients with CSDs. Full article

Atherosclerosis, a condition characterized by the accumulation of lipids and a culprit behind cardiovascular events, has long been studied. However, in recent years, there has been an increase in interest in its initiation, with researchers shifting focus from traditional pathways involving the vascular infiltration of oxidized lipids and towards the novel presence of chronic inflammatory pathways. The accumulation of pro-inflammatory cytokines, in combination with the activation of transcription factors, creates a positive feedback loop that drives the creation and progression of atherosclerosis. From the upregulation of the nod-like receptor protein 3 (NLRP3) inflammasome and the Notch and Wnt pathways to the increased expression of VEGF-A and the downregulation of connexins Cx32, Cx37, and Cx40, these processes contribute further to endothelial dysfunction and plaque formation. Herein, we aim to provide insight into the molecular pathways and mechanisms implicated in the initiation and progression of atherosclerotic plaques, and to review the risk factors associated with their development. Full article

Background/Objectives: The aim of the present study was to evaluate the relationship between the type of scapular notch (SN), the morphometry of the SN, and the area of the suprascapular nerve (SSN). In addition to determining whether scapular notches other than Type VI, according to the classification of Rengachary, can generate a predisposition to SSN entrapment neuropathy. Methods: One hundred and sixty-nine dry scapulae were examined, the scapular notches were classified, according to the classification of Rengachary, and for each SN, the superior transverse diameter (STD), longitudinal diameter (LD), and area of the SN were determined. The SSN was dissected in five shoulders and its area was calculated. The data were analyzed in the statistical software SPSS. Results: The values for the STD, LD, and area of the SN showed significant differences between the types of scapular notches (p < 0.0001). Along the same lines, a considerable positive correlation (r = 0.79; p < 0.0001) was established between the area of the SN and the STD. Similarly, a very strong positive correlation (r = 0.87; p < 0.0001) was established between the area of the SN and the LD. This indicated that, as the STD and the LD increase, the area of the SN increases. Conclusions: Although different studies have reported an association between SN Type VI and the compression of the SSN by the formation of a bony hole that reduces the area of the notch, we have found that SN Type IV presented a smaller area among the types of notches and a smaller area than the SSN, which exposes the SSN to be closer to or in contact with the superior transverse ligament of the scapula, potentially subjecting the nerve to greater pressure and potentially resulting in SSN entrapment. This is evidence that should be considered in the clinical diagnosis of patients with entrapment neuropathy, since the type of SN and the area of the SSN can be determined by ultrasound, which contributes to a more accurate preoperative evaluation and diagnosis. Full article

Background/Objectives: Classical reverse shoulder arthroplasty (RSA) with a high neck–shaft angle (NSA) of 155° has shown satisfactory outcomes. However, newer RSA designs aim to improve results by modifying the stem design. This study evaluates the 5-year outcomes of a stem design featuring a rectangular metadiaphyseal fixation and a 135° NSA. Methods: This prospective bicentric case series included and longitudinally followed up patients that were treated for cuff arthropathy, massive irreparable rotator cuff tears, or eccentric osteoarthritis using a non-cemented rectangular metadiaphyseal fixation stem with a 135° NSA (Univers Revers, Arthrex, Naples, FL, USA). Subjective and objective functional outcome scores (Constant–Murley Score (CS), Shoulder Pain and Disability Index (SPADI), and Subjective Shoulder Value (SSV)), range of motion (ROM), radiographic outcome, adverse events, complications, and quality of life were investigated. Results: This study enrolled 132 patients (59% female, mean age 75 years, SD 6). At the 5-year follow-up, subjective and objective outcomes significantly improved compared to baseline: CS (32.9 to 71.7, p < 0.001), SPADI (38.7 to 86.2, p < 0.001), and SSV (43.0 to 84.1, p < 0.001). ROM improved in flexion (80° to 142.4°, p < 0.001), abduction (71.5° to 130.2°, p < 0.001), internal rotation (p < 0.001), internal rotation at 90° abduction (12.7° to 45.0°, p < 0.001), and abduction strength (0.8 kg to 5.2 kg, p < 0.001). External rotation remained unchanged (32.1° to 32.0°, p = 0.125), but external rotation at 90° abduction improved (20.9° to 52.7°, p < 0.001). No signs of implant migration, subsidence, shift, tilt, alignment loss, or wear were observed, but scapular bone spur formation (11%), scapular notching grade 1 (10%), bone resorption (10%), and partial humeral radiolucent lines (1%) were reported. Conclusions: Rectangular stems with metadiaphyseal fixation and a 135° neck–shaft angle in RSA consistently improve shoulder function, showing no aseptic loosening and minimal radiological changes at 5 years. Full article

Cancer stem cells (CSC) are known to be the main source of tumor relapse, metastasis, or multidrug resistance and the mechanisms to counteract or eradicate them and their activity remain elusive. There are different hypotheses that claim that the origin of CSC might be in regular stem cells (SC) and, due to accumulation of mutations, these normal cells become malignant, or the source of CSC might be in any malignant cell that, under certain environmental circumstances, acquires all the qualities to become CSC. Multiple studies indicate that lifestyle and diet might represent a source of wellbeing that can prevent and ameliorate the malignant phenotype of CSC. In this review, after a brief introduction to SC and CSC, we analyze the effects of phenolic and non-phenolic dietary compounds and we highlight the molecular mechanisms that are shown to link diets to CSC activation in colon, breast, and prostate cancer. We focus the analysis on specific markers such as sphere formation, CD surface markers, epithelial–mesenchymal transition (EMT), Oct4, Nanog, Sox2, and aldehyde dehydrogenase 1 (ALDH1) and on the major signaling pathways such as PI3K/Akt/mTOR, NF-κB, Notch, Hedgehog, and Wnt/β-catenin in CSC. In conclusion, a better understanding of how bioactive compounds in our diets influence the dynamics of CSC can raise valuable awareness towards reducing cancer risk. Full article

The fracture process of heterogeneous materials is studied here in the framework of the discipline of Non-Extensive Statistical Mechanics. Acoustic emission data provided by an experimental protocol with concrete specimens, plain or fiber-reinforced, under bending are taken advantage of. This innovation of the study lies in the fact that the analysis of the acoustic activity is implemented in terms of the energy content of the acoustic signals rather than of their interevent time or their interevent distance. The Energy Distribution Functions were properly fitted using the expression proposed by Shcherbakov, Kuksenko and Chmelet. This study reveals that the loading and fracture processes of the specific materials are definitely non-additive and non-extensive. It is concluded that the presence of notches is crucial since it assigns non-additivity and non-extensivity from relatively low loading levels due to the early formation of the fracture process zone around the crown of the notch. The values of the Tsallis entropic index, q, that were determined are in very good agreement with the respective ones obtained in previous studies by means of different analysis tools. Finally, a clear correlation between the index q and the average energy content of the acoustic signals is highlighted for the whole range of values of the energy content of the acoustic signals. Full article

Ovarian cancer (OC) is the second most common female reproductive cancer and the most lethal gynecological malignancy worldwide. Most human OCs are characterized by high rates of drug resistance and metastasis, leading to poor prognosis. Improving the outcomes of patients with relapsed and treatment-resistant OC remains a challenge. This study aimed to investigate the role of epidermal growth factor-like domain 8 (EGFL8) in human OC by examining the effects of siRNA-mediated EGFL8 knockdown on cancer progression. EGFL8 knockdown in human OC cells promoted aggressive traits associated with cancer progression, including enhanced proliferation, colony formation, migration, invasion, chemoresistance, and reduced apoptosis. Additionally, knockdown upregulated the expression of epithelial–mesenchymal transition (EMT) markers (Snail, Twist1, Zeb1, Zeb2, and vimentin) and cancer stem cell biomarkers (Oct4, Sox2, Nanog, KLF4, and ALDH1A1), and increased the expression of matrix metallopeptidases (MMP-2 and MMP-9), drug resistance genes (MDR1 and MRP1), and Notch1. Low EGFL8 expression also correlated with poor prognosis in human OC. Overall, this study provides crucial evidence that EGFL8 inhibits the proliferation and cancer aggressiveness of human OC cells by suppressing ERK/MAPK signaling. Therefore, EGFL8 may serve as a valuable prognostic biomarker and a potential target for developing novel human OC therapies. Full article

This study aims to explore the effect of microstructural parameters on the notch fatigue damage behavior of the TC21 alloy. Different levels of lamellar microstructures were achieved through distinct aging temperatures of 550 °C, 600 °C, and 650 °C. The findings reveal that increasing aging temperature primarily contributes to the augmentation of α colony (α_c) thickness, grain boundaries α phase (GBα) thickness, and α fine (α_fine) size alongside a reduction in α lath (α_lath) thickness and α_fine content. The notch alters stress distribution and relaxation effects at the root, enhancing notched tensile strength while weakening plasticity. Moreover, the increased thickness of GBα emerges as a critical factor leading to the increase area of intergranular cleavage fracture. It is noteworthy that more thickness α_lath and smaller α_fine facilitate deformation coordination and enhance dislocation accumulation at the interface, leading to a higher propensity for micro-voids and micro-cracks to propagate along the interface. Conversely, at elevated aging temperatures, thinner α_lath and larger α_fine are more susceptible to fracture, resulting in the liberation of dislocations at the interface. The reduction in α_lath thickness is crucial for triggering the initiation of multi-system dislocations at the interface, which promotes the development of persistent slip bands (PSBs) and dislocation nets within α_lath. This phenomenon induces inhomogeneous plastic deformation and localized hardening, fostering the formation of micro-voids and micro-cracks. Full article

The placenta is a vital organ that supports fetal development by mediating nutrient and gas exchange, regulating immune tolerance, and maintaining hormonal balance. Its formation and function are tightly linked to the processes of embryo implantation and the establishment of a robust placental-uterine interface. Recent advances in molecular biology and histopathology have shed light on the key regulatory factors governing these processes, including trophoblast invasion, spiral artery remodeling, and the development of chorionic villi. This review integrates morphological and molecular perspectives on placental development, emphasizing the roles of cytokines, growth factors, and signaling pathways, such as VEGF and Notch signaling, in orchestrating implantation and placental formation. The intricate interplay between molecular regulation and morphological adaptations highlights the placenta’s critical role as a dynamic interface in pregnancy. This review synthesizes current findings to offer clinicians and researchers a comprehensive understanding of the placenta’s role in implantation, emphasizing its importance in maternal-fetal medicine. By integrating these insights, the review lays the groundwork for advancing diagnostic and therapeutic approaches that can enhance pregnancy outcomes and address related complications effectively. Full article

This paper presents a novel numerical investigation into the air cushion effect and impact loads during the water entry of notched discs, utilizing the Structured Arbitrary Lagrangian–Eulerian (S-ALE) algorithm in LS-DYNA. Unlike prior studies that focused on smooth or unnotched geometries, the present study explores how varying notch parameters influence the fluid–solid coupling process during high-speed water entry. The reliability and accuracy of the computational method are validated through grid independence verification and comparisons with experimental data and empirical formulas. Systematic analysis of the effects of notch size, water entry velocity, and entry angle on the evolution of the free surface, impact loads, and structural responses uncovers several novel findings. Notably, increasing the notch diameter significantly enhances the formation and stability of the air cushion, leading to a considerable reduction in peak impact loads—a phenomenon not previously quantified. Additionally, higher water entry Froude numbers are shown to accelerate air cushion compression and formation, markedly affecting free surface morphology and force distribution. The results also reveal that varying the water entry angle alters the air cushion’s morphological characteristics, where larger angles induce a more pronounced but less stable air cushion, influencing the internal structural response differently across regions. Full article

The transcription factor Runx2 plays a crucial role in regulating osteogenic differentiation and skeletal development. This factor not only controls the expression of genes involved in bone formation, but also interacts with signaling pathways such as the Notch pathway, which are essential for body development. However, studies have produced conflicting results regarding the relationship between Runx2 and the Notch pathway. Some studies suggest a synergistic interaction between these molecules, while others suggest an inhibitory one, for example, the interplay between Notch signaling, Runx2, and vitamin D3 in osteogenic differentiation and bone remodeling. The findings suggest a complex relationship between Notch signaling and osteogenic differentiation, with ongoing research needed to clarify the mechanisms involved and resolve existing contradictions regarding role of Notch in this process. Additionally, there is increasing evidence of contradictory roles for Runx2 in various tissues and organs, both under normal conditions and in pathological states. This diversity of roles makes Runx2 a potential therapeutic target, offering new directions for research. In this review, we have discussed the mechanisms of osteogenic differentiation and the important role of Runx2 in this process. We have also examined its relationship with different signaling pathways. However, there are still many uncertainties and inconsistencies in our current understanding of these interactions. Additionally, given that Runx2 is also involved in numerous other events in various tissues, we have tried to comprehensively examine its functions outside the skeletal system. Full article

Notch signaling, an important signaling pathway in cardiac development, has been shown to mediate the reparative functions of c-kit+ progenitor cells (CPCs). However, it is unclear how each of the four canonical Notch-activating ligands affects intracellular processes in c-kit+ cells when used as an external stimulus. Neonatal c-kit+ CPCs were stimulated using four different chimeric Notch-activating ligands tethered to Dynabeads, and the resulting changes were assessed using TaqMan gene expression arrays, with subsequent analysis by principal component analysis (PCA). Additionally, functional outcomes were measured using an endothelial cell tube formation assay and MSC migration assay to assess the paracrine capacity to stimulate new vessel formation and recruit other reparative cell types to the site of injury. Gene expression data showed that stimulation with Jagged-1 is associated with the greatest pro-angiogenic gene response, including the expression of VEGF and basement membrane proteins, while the other canonical ligands, Jagged-2, Dll-1, and Dll-4, are more associated with regulatory and epigenetic changes. The functional assay showed differential responses to the four ligands in terms of angiogenesis, while none of the ligands produced a robust change in migration. These data demonstrate how the four Notch-activating ligands differentially regulate CPC gene expression and function. Full article

This study investigates the role of coalesced bainite in enhancing the hydrogen embrittlement resistance of tempered martensitic steels. By analyzing the microstructural characteristics and mechanical properties under varying cooling rates, it was found that the presence of coalesced bainite significantly impedes hydrogen accumulation at prior austenite grain boundaries. This leads to a transition in the fracture mode from intergranular to transgranular, thereby improving the overall resistance to hydrogen embrittlement in steels. Slow strain rate tests (SSRTs) on both smooth and notched specimens further confirmed that steels cooled at lower rates, which form a higher fraction of coalesced bainite, exhibiting superior hydrogen embrittlement resistance. These findings suggest that optimizing the cooling process to promote coalesced bainite formation could be a valuable strategy for enhancing the performance of tempered martensitic steels in hydrogen-rich environments. Full article

Bone remodeling is an intricate process executed throughout one’s whole life via the cross-talk of several cellular events, progenitor cells and signaling pathways. It is an imperative mechanism for regaining bone loss, recovering damaged tissue and repairing fractures. To achieve this, molecular signaling pathways play a central role in regulating pathological and causal mechanisms in different diseases. Similarly, microRNAs (miRNAs) have shown promising results in disease management by mediating mRNA targeted gene expression and post-transcriptional gene function. However, the role and relevance of these miRNAs in signaling processes, which regulate the delicate balance between bone formation and bone resorption, are unclear. This review aims to summarize current knowledge of bone remodeling from two perspectives: firstly, we outline the modus operandi of five major molecular signaling pathways, i.e.,the receptor activator of nuclear factor kappa-B (RANK)-osteoprotegrin (OPG) and RANK ligand (RANK-OPG-RANKL), macrophage colony-stimulating factor (M-CSF), Wnt/β-catenin, Jagged/Notch and bone morphogenetic protein (BMP) pathways in regards to bone cell formation and function; and secondly, the miRNAs that participate in these pathways are introduced. Probing the miRNA-mediated regulation of these pathways may help in preparing the foundation for developing targeted strategies in bone remodeling, repair and regeneration. Full article

Galectin-3 (Gal-3) is a pleiotropic lectin produced by most cell types, which regulates multiple cellular processes in various tissues. In bone, depending on its cellular localization, Gal-3 has a dual and opposite role. If, on the one hand, intracellular Gal-3 promotes bone formation, on the other, its circulating form affects bone remodeling, antagonizing osteoblast differentiation and increasing osteoclast activity. From an analysis of the secretome of cultured differentiating myoblasts, we interestingly found the presence of Gal-3. After that, we confirmed that Gal-3 was expressed and released in the extracellular environment from myoblast cells during their differentiation into myotubes, as well as after mechanical strain. An in vivo analysis revealed that Gal-3 was triggered by trained exercise and was specifically produced by fast muscle fibers. Speculating a role for this peptide in the muscle-to-bone cross talk, a direct co-culture in vitro system, simultaneously combining media that were obtained from differentiated myoblasts and osteoblast cells, confirmed that Gal-3 is a mediator of osteoblast differentiation. Molecular and proteomic analyses revealed that the secreted Gal-3 modulated the biochemical processes occurring in the early phases of bone formation, in particular impairing the activity of the STAT3 and PDK1/Akt signaling pathways and, at the same time, triggering that one of Notch. Circulating Gal-3 also affected the expression of the most common factors involved in osteogenetic processes, including BMP-2, -6, and -7. Intriguingly, Gal-3 was able to interfere with the ability of differentiating osteoblasts to interact with the components of the extracellular bone matrix, a crucial condition required for a proper osteoblast differentiation. All in all, our evidence lays the foundation for further studies to present this lectin as a novel myokine involved in muscle-to-bone crosstalk. Full article