Search Results (131)

The capacity of plants to generate new organs and tissues throughout their life cycle depends on the activity of the stem cells contained in meristematic tissues. Plant stem cells are organized in small, clustered populations referred to as stem cell niches. In addition to generating new undifferentiated cells, stem cell niches also provide the positional information that maintains stem cell self-renewal properties and controls the non-cell-autonomous differentiation of surrounding tissues. In this review, we aim to analyze and discuss the most recent literature describing the molecular mechanism controlling the activity and the organization of the stem cell niche in the root of the model plant Arabidopsis thaliana (L.) Heynh. In particular, we will focus on the complex molecular regulatory networks that control the balance between stemness and differentiation in distal stem cells, as well as the maintenance of the mitotically inactive state of the quiescent center. Full article

Background and objectives: The objective was to validate the Beyond the Vancouver classification. Based on this algorithm, it was hypothesized that cemented polished tapered stems with an intact cement mantle and cementless stable stems with defined criteria could be classified as stable and therefore treated with open reduction and internal fixation (ORIF). Materials and Methods: This retrospective, single-center cohort study re-analyzed patients initially diagnosed with Vancouver type B2 fractures treated with ORIF between 2007 and 2020. Clinical and radiological outcomes were extracted from medical reports. A combined radiological and clinical score was used as the main outcome measure. Patients categorized according to the Beyond the Vancouver classification were compared for functional outcome. Results: 42 patients (25 male, 17 female) with a median (range) age of 83 years (75–88 years) and follow-up time of 25 weeks (12–35 weeks) were reviewed. It was found that ORIF achieved excellent or good results in 81% of cases for stems classified as stable (n = 16) and in 30% of cases for stems classified as loose (n = 23). Successful cases (30%), although classified as loose, all had the same fracture pattern: an intact greater trochanter and a fracture fragment attached laterally to the stem with distal fixation of the stem. Conclusions: This case series suggests that certain Vancouver B2 fractures can be treated with ORIF. The Beyond the Vancouver classification may support the categorization of ‘stable’ and ‘loose’ stems. The validity of the algorithm was supported by the observation that ORIF provided excellent and good results for the majority of stems classified as ‘stable’, but poor results for stems classified as ‘loose’. Furthermore, the fracture pattern has been shown to be a crucial factor that should be considered when treating distally fixed cementless stems. The classification was therefore expanded to include the specific fracture patterns in cementless distally fixed stems that can be successfully treated with ORIF. The Beyond the Vancouver classification can provide further guidance in the identification of ‘loose’ or ‘stable’ stems. Full article

Background: Stress shielding (SS) after total hip arthroplasty (THA) leads to proximal femoral bone loss and increases the risk of complications such as implant loosening and periprosthetic fracture. While various low-stiffness stems have been developed to prevent SS, they often compromise mechanical stability. A novel femoral stem composed of Ti-33.6Nb-4Sn (TNS) alloy offers a gradually decreasing Young’s modulus from proximal to distal regions, potentially improving load distribution and reducing SS. This study aimed to evaluate the mid-term clinical and radiographic outcomes of the TNS stem, with a particular focus on its effectiveness in suppressing SS. Methods: A prospective clinical study was conducted involving 35 patients who underwent THA using the TNS stem, with a minimum follow-up of 7 years. Twenty-one patients with Ti6Al4V metaphyseal-filling stems served as controls. Clinical outcomes were assessed using Japanese Orthopaedic Association (JOA) scores, and radiographic SS was graded using Engh’s classification and analyzed in Gruen zones. Inter-examiner reliability and statistical comparisons between groups were performed using appropriate tests. Results: The TNS group showed significantly higher preoperative JOA scores than the control group, but no significant difference in final scores. Both groups demonstrated significant improvement postoperatively. Third-degree SS occurred in the TNS group, although the overall SS grade distribution was significantly lower than in the control group (p = 0.03). SS frequency was significantly reduced in Gruen Zones 2, 3, and 6 in the TNS group. Conclusions: The TNS stem demonstrated a significant reduction in SS progression compared to conventional titanium stems over a 7-year period, with comparable clinical outcomes. However, the occurrence of third-degree SS indicates that material optimization alone may be insufficient, highlighting the need for further design improvements. Full article

Stress shielding remains a major concern in cementless total hip arthroplasty (THA) due to the stiffness mismatch between femoral stems and surrounding bone. This study investigated the biomechanical and clinical performance of a novel Ti-33.6Nb-4Sn (Ti-Nb-Sn) alloy stem with a graded Young’s modulus achieved through localized heat treatment. A finite element model (FEM) of the Ti-Nb-Sn stem, incorporating experimentally validated Young’s modulus gradients, was constructed and implanted into a patient-specific femoral model. Stress distribution and micromotion were assessed under physiological loading conditions. Clinical validation was performed by evaluating radiographic outcomes at 1 and 3 years postoperatively in 40 patients who underwent THA using the Ti-Nb-Sn stem. FEM analysis showed low micromotion at the proximal press-fit region (4.89 μm rotational and 11.74 μm longitudinal), well below the threshold for osseointegration and loosening. Stress distribution was concentrated in the proximal region, effectively reducing stress shielding distally. Clinical results demonstrated minimal stress shielding, with no cases exceeding Grade 3 according to Engh’s classification. The Ti-Nb-Sn stem with a gradient Young’s modulus provided biomechanical behavior closely resembling in vivo conditions and showed promising clinical results in minimizing stress shielding. These findings support the clinical potential of modulus-graded Ti-Nb-Sn stems for improving implant stability in THA. Full article

Objective: The increasing number of aging patients with total hip arthroplasties (THA) causes an increased incidence of periprosthetic fractures (PPF). The study aimed to evaluate the impacts of two different materials in the same-sized cemented stems on PPF in bone models. Methods: This study compared the maximum rotational torque leading to PPF when stems made of cobalt–chromium–molybdenum (Co–Cr–Mo) alloy and stainless use steel (SUS) were implanted using simulated bone models (Sawbones, 3403). The maximum destruction torque was compared statistically for each material (Co–Cr–Mo alloy vs. SUS stainless steel) in this model, and fracture patterns were examined. Results: The PPF occurred with a spiral propagation from the proximal femur towards the diaphysis, with breakage occurring near the distal end of the stem. There were no significant differences in the destruction torque values between the Co–Cr–Mo alloy (103.0 ± 14.9 Nm) and SUS (98.7 ± 15.1 Nm) samples (p = 0.575). The fractures using the bone models exhibited similar patterns in all specimens, resembling clinical PPF fracture types clinically, specifically Vancouver classification B2. Conclusions: The comparison of the maximum destruction torques of the Co–Cr–Mo alloy and SUS cemented stems in simulating PPF showed no significant differences. The results suggest that the materials of the cemented stems might not significantly affect the occurrence of PPF in THA. Full article

This paper presents an experimental and numerical analysis of the mechanical behaviour of orthopaedic implants with crack-type defects, considering the principles and advantages of the modern X-FEM method, which was used due to limitations of traditional FEM in terms of crack growth simulation, especially for complex geometries. In X-FEM, the finite element space is enriched with discontinuity functions and asymptotic functions at the crack tip, which are integrated into the standard finite element approximation using the unity division property. Though rare, femoral component failures are well-documented complications that can occur after hip prosthetic implantation. Most stem fractures happen in the first third of the implant due to the loosening of the proximal stem and fixation of the distal stem, leading to bending and eventual fatigue failure. The main goal of this paper was to obtain accurate and representative models of such failures. Experimental analyses of the mechanical behaviour of implants subjected to physiological loads, according to relevant standards, using a new combined approach, including both experiments and numerical simulations was presented. The goal was to verify the numerical results and obtain a novel, effective methodology for assessing the remaining fatigue life of hip implants. For this purpose, the analysis of the influence of Paris coefficients on the total number of cycles was also considered. Hence, this simulation involved defining loads to closely mimic real-life scenarios, including a combination of activities such as ascending stairs, stumbling, and descending stairs. The tensile properties of the titanium alloy were experimentally determined, along with the Paris law coefficients C and m. The finite element software ANSYS 2022R2 version was used to develop and calculate the three-dimensional model with a crack, and the resulting stresses, stress intensity factors, and the number of cycles presented in the figures, tables, and diagrams. The results for the fatigue life of a partial hip implant subjected to various load cases indicated significant differences in behaviour, and this underscores the importance of analysing each case individually, as these loads are heavily influenced by each patient’s specific activities. It was concluded that the use of numerical methods enabled the preliminary analyses of the mechanical behaviour of implants under fatigue loading for several different load cases, and these findings can be effectively used to predict the possibility of Ti-6Al-4V implant failure under variable cyclic loads. Full article

Background: Cuscuta australis R. Br. is a parasitic herbaceous plant that obtains nutrients by forming specialized structures called haustoria to invade host plants. Methods: In this study, we elucidated the differences in the gene expression regulation and metabolic characteristics between Cuscuta australis and Glycine max (Glycine max (L.) Merr. Var Williams) through comprehensive transcriptomic and metabolomic analyses. Results: The results demonstrated significant differences in the gene expression and metabolic features between the haustorium and the distal stem segments. The differentially expressed genes absorbed by Cuscuta australis from the soybean host influence amino acid metabolism, and the expression of the S-adenosylmethionine decarboxylase gene may affect the production of 5′-methylthioadenosine. A high expression of the chalcone synthase enzyme could lead to an increased daidzein content. Many Glycine max genes were also integrated into Cuscuta australis within the haustorium. Conclusions: This study systematically analyzed, for the first time, the significant differences in gene expression and metabolic characteristics between the haustoria and distal stem segments of Cuscuta. It also explored the nutrient absorption mechanisms of the host plant. Additionally, the research discovered that Cuscuta can absorb a substantial amount of host genes and adapt to its parasitic lifestyle through differential gene expression and metabolic changes. These findings provide important insights into the parasitic mechanisms of Cuscuta australis and lay the foundation for the development of effective control strategies. Full article

Dysregulated iron metabolism-induced ferroptosis is considered a key pathological mechanism in the development of osteoporosis (OP). G protein-coupled receptor 30 (GPR30, also known as Gper1) is an estrogen-binding receptor that has shown therapeutic benefits in patients with certain degenerative diseases. Moreover, several studies have demonstrated the anti-ferroptotic effects of estrogen receptor activation. However, its role in the prevention and treatment of OP remains unclear, and there are currently no reports on the anti-ferroptotic function of GPR30 in OP. Therefore, this study aimed to investigate the ferroptosis-related effects and mechanisms of GPR30 in the context of OP. In vivo and in vitro experiments were conducted using wild-type (WT) C57BL/6 female mice and GPR30-knockout (GPR30-KO) C57BL/6J female mice. The microarchitecture of the distal femur was assessed using micro-computed tomography (micro-CT), and histomorphological changes were analyzed via hematoxylin and eosin (H&E) staining. Bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured to establish an iron overload model using ferric ammonium citrate (FAC). Interventions included GPR30 overexpression via transfection and BMP-6 inhibition using LDN-214117. Cell viability was evaluated with the CCK-8 assay, while osteogenic differentiation and mineralization levels were assessed using ALP and Alizarin Red S (ARS) staining. Iron accumulation was detected via Prussian blue staining, oxidative stress levels were evaluated using ROS staining, and mitochondrial membrane potential changes were analyzed using JC-1 staining. Transmission electron microscopy (TEM) was employed to observe mitochondrial ultrastructural changes. Additionally, key gene and protein expression levels were measured using immunofluorescence and Western blotting. The micro-CT analysis revealed significant bone microarchitecture deterioration and bone loss in the GPR30-KO mouse model. At the cellular level, GPR30 overexpression markedly reduced iron accumulation and oxidative stress in BMSCs, restored the mitochondrial membrane potential, and improved the mitochondrial ultrastructure. Furthermore, GPR30 enhanced osteogenic differentiation in BMSCs by promoting the activation of the BMP-6/HEP/FPN signaling pathway, leading to increased expression of osteogenic markers. The protective effects of GPR30 were reversed by the BMP-6 inhibitor LDN-214117, indicating that BMP-6 is a critical mediator in GPR30-regulated iron metabolism and ferroptosis inhibition. GPR30 inhibits ferroptosis in BMSCs and enhances osteogenic differentiation by activating the BMP-6/HEP/FPN signaling pathway. This provides new insights and potential therapeutic targets for the treatment of osteoporosis OP. Full article

Caudal regression syndrome (CRS) is a malformation that occurs during the fetal period, and is mainly characterized by the incomplete development of the spinal cord (SC), which is often accompanied by other developmental abnormalities. The present study was performed in a 2-month-old boy with CRS, born to a type I diabetic mother, who presented interruption of the SC at the L5–L4 level, pelvic dislocation, sacral agenesis, hypoplastic femurs, lack of innervation of the lower limbs (spastic paraplegia), and a neurogenic bladder and bowel. Given the positive results we obtained in a previous study in a similar case, this patient was treated with GH (0.04 mg/kg/day, 5 days/week), melatonin (20 mg/day), and rehabilitation. The treatment only lasted 18 months, due to family problems. Blood tests and physical examinations were performed every 3 months initially and then every 6 months. Interestingly, despite GH administration, the child presented low plasma glucose and IGF-I values, which did not increase throughout the treatment, although there was significant growth of the patient, also indicated by elevated plasma alkaline phosphatase values. At the end of treatment, the gross motor function test (GMFM)-88 score increased from 0.93 (on admission) to 47.94. Sensory responses appeared in the lower limbs, and the patient was able to move his leg muscles in all directions and control his sphincters. Ten months after discharge, the patient was able to walk only with the aid of a back walker. GH treatment did not produce any adverse effects. In summary, despite the short duration of treatment, GH plus rehabilitation has been useful in innervating distal areas below the level of the incomplete spinal cord in CRS. GH likely acted on ependymal neural stem cells, as the hormone does on neurogenic niches in the brain, and rehabilitation helped achieve near-full functionality. Full article

The stability of the tibial component in Total Knee Arthroplasty (TKA) is critical to preventing aseptic loosening, a major cause of implant failure. However, existing tibial stem designs often lead to stress shielding and bone resorption, highlighting the need for further optimization. This study addresses these challenges by employing the Design of Experiments (DOE) methodology, specifically utilizing a full factorial design approach combined with finite element analysis (FEA), to optimize the geometry of the tibial stem. The material properties of the cortical and cancellous bone, as well as the tibial tray, were assigned based on values from the literature, representing their elastic moduli and Poisson’s ratios. For boundary conditions, the distal end of the tibia was fully constrained to simulate realistic load transfer, while compressive loads representative of walking and daily activities were applied to the tibial base. Key design parameters, including stem diameter, length, mediolateral ratio (M/L ratio), and wing angle, were systematically analyzed. The results identified stem diameter and length as the most influential factors in improving biomechanical performance, while the wing angle showed minimal impact. The optimized design, featuring a stem diameter of 12 mm, length of 40 mm, M/L ratio of 0.61, and a wing angle of 60°, demonstrated significant reductions in stress shielding and aseptic loosening compared to conventional models. These findings provide valuable insights into enhancing the long-term success of TKA implants by balancing implant stability and minimizing bone resection. Full article

Background/Objectives: Stress concentration around distal screw-removal holes confers a major risk for periprosthetic fractures following conversion total hip arthroplasty (cTHA) for intertrochanteric femoral fractures. Optimal stem-selection criteria and guidelines for cTHA can improve clinical outcomes. We determined the influence of the cementless stem length on the stress distribution around distal screw-removal holes. Methods: For the finite element analysis, institutional data from preoperative CT scans of contralateral femurs of patients who underwent THA were used. To replicate the post-nail-removal state, we used 3D registration of standard triangulated language data of the intramedullary nail as an unused material to simulate distal screw-removal holes, located 135 mm from the proximal end of the intramedullary nail. Cementless stems of 130, 140, 150, and 160 mm were individually registered using STL data, and cTHA models were constructed accordingly. Using simulations under load conditions representing normal walking and stair climbing, the mean and maximum equivalent stress values around the distal screw-removal holes were calculated. For multiple comparisons, repeated-measures ANOVA with Bonferroni correction was employed. Results: Compared to the 130 mm stem, the 150 mm and 160 mm stems similarly reduced the maximum equivalent stress around the distal screw-removal holes, although the 140 mm stem showed no significant difference with other stems. Conclusions: A ≥150 mm stem length reliably mitigated stress concentration around distal screw-removal holes post-cTHA; it is the optimal choice for balancing effectiveness and risk of complications and may contribute to improved long-term clinical outcomes. This study provides practical evidence for stem selection in cTHA and offers valuable insights for future treatment guidelines. Full article

Background and Objectives: The study aimed to evaluate a newly designed semicircular implant for the fixation of Vancouver Type B1 periprosthetic femoral fractures (PFFs) in total hip arthroplasty (THA) patients. To determine its strength and clinical applicability, the new implant was compared biomechanically with conventional fixation methods, such as lateral locking plate fixation and a plate combined with cerclage wires. Materials and Methods: Fifteen synthetic femur models were used in this biomechanical study. A Vancouver Type B1 periprosthetic fracture was simulated by osteotomy 5 mm distal to the femoral stem. The models were divided into three groups: Group I (lateral locking plate fixation), Group II (lateral locking plate with cerclage wires), and Group III (new semicircular implant system). All fixation methods were subjected to axial loading, lateral bending, and torsional force testing using an MTS biomechanical testing device. Failure load and displacement were measured to assess stability. Results: The semicircular implant (Group III) demonstrated a significantly higher failure load (778.8 ± 74.089 N) compared to the lateral plate (Group I: 467 ± 68.165 N) and plate with cerclage wires (Group II: 652.4 ± 65.474 N; p < 0.001). The new implant also exhibited superior stability under axial, lateral bending, and torsional forces. The failure load for Group III was more robust, with fractures occurring at the screw level rather than plate or screw detachment. Conclusions: Compared to traditional fixation methods, the newly designed semicircular implant demonstrated superior biomechanical performance in stabilizing Vancouver Type B1 periprosthetic femoral fractures. It withstood higher physiological loads, offered better structural stability, and could be an alternative to existing fixation systems in clinical practice. Further studies, including cadaveric and in vivo trials, are recommended to confirm these results and assess the long-term clinical outcomes. Full article

Mammalian blood cells originate from specialized ‘hemogenic’ endothelial (HE) cells in major arteries. During the endothelial-to-hematopoietic transition (EHT), nascent hematopoietic stem cells (HSCs) bud from the arterial endothelial wall and enter circulation, destined to colonize the fetal liver before ultimately migrating to the bone marrow. Mechanisms and processes that facilitate EHT and the release of nascent HSCs are incompletely understood, but may involve signaling from neighboring vascular endothelial cells, stromal support cells, circulating pre-formed hematopoietic cells, and/or systemic factors secreted by distal organs. We used single cell RNA sequencing analysis from human embryonic cells to identify relevant signaling pathways that support nascent HSC release. In addition to intercellular and secreted signaling modalities that have been previously functionally validated to support EHT and/or developmental hematopoiesis in model systems, we identify several novel modalities with plausible mechanisms to support EHT and HSC release. Our findings paint a portrait of the complex inter-regulated signals from the local niche, circulating hematopoietic/inflammatory cells, and distal fetal liver that support hematopoiesis. Full article

Background/Objectives: Proximal femoral fractures are particularly common in older adults, and cases requiring conversion to total hip arthroplasty may arise because of treatment failure or osteoarthritis. Fractures around the distal screw removal holes can be problematic. This study aimed to analyze the relationship between stem length and femoral stress distribution to determine the optimal stem length. Methods: A finite element analysis simulation was conducted using pre-existing femoral computed tomography data, an intramedullary nail, and three types of stems of varying lengths. Loads simulating normal walking and stair climbing were applied, and the average and maximum equivalent stresses were measured on both the medial and lateral sides of the distal screw removal hole for each stem length. Statistical analysis was then performed to evaluate the stress distributions. Results: The average stress around the distal screw removal hole tended to decrease as stem length increased. The maximum stress was significantly lower with the 160-mm stem, which provides a 40-mm bridging length, compared to the 120-mm and 130-mm stems, where the stem tip aligned with or only slightly extended past the distal screw removal hole (bridging lengths of 0 mm and 10 mm, respectively). Conclusions: In conversion hip total arthroplasty following proximal femoral fractures, using a sufficiently long stem can help avoid stress concentration around the distal screw removal hole, thereby potentially reducing the risk of periprosthetic fractures. Full article

Diabetes mellitus (DM) is a global health concern with a rising incidence, particularly in aging populations and those with a genetic predisposition. Over time, DM contributes to various complications, including nephropathy, retinopathy, peripheral arterial disease (PAD), and neuropathy. Among these, diabetic neuropathy and PAD stand out due to their high prevalence and significant impact on patients’ quality of life. Diabetic distal symmetric polyneuropathy, the most common form of diabetic neuropathy, is driven by neuroinflammation stemming from prolonged hyperglycemia. Simultaneously, hyperglycemia significantly increases the risk of PAD, a condition further exacerbated by factors like smoking, age, and sedentary lifestyles. PAD frequently manifests as claudication, a debilitating symptom marked by pain and cramping during physical activity, which limits mobility and worsens patients’ outcomes. Cilostazol, a phosphodiesterase-3 inhibitor, has proven effective in managing intermittent claudication in PAD by improving walking distances and enhancing blood flow. Recent studies have also explored its potential benefits for diabetic neuropathy. Cilostazol’s mechanisms include vasodilation, platelet inhibition, and increased cyclic adenosine monophosphate (cAMP) levels, which may contribute to improved neurological outcomes. However, variability in the clinical evidence due to inconsistent treatment protocols highlights the need for further investigation. This review explores cilostazol’s mechanisms of action and therapeutic applications for managing neuropathy and PAD in diabetic patients, aiming to provide insights into its potential as a dual-purpose pharmacological agent in this high-risk population. Full article