-
The American Surgeon Jun 2024Musicians with physical disabilities who achieved stardom are part of the lore of popular music. Guitarist Django Reinhardt contrived alternate fingering patterns...
Musicians with physical disabilities who achieved stardom are part of the lore of popular music. Guitarist Django Reinhardt contrived alternate fingering patterns necessitated by burn contractures of his left hand. Les Paul, a legend in the development of the solid body electric guitar and multitrack recording, mangled his right arm in a car wreck so severely that his elbow was set permanently at 90° so he could continue to play guitar. Michel Petrucciani suffered from osteogenesis imperfecta, a condition that stunted his growth to the point where he used a special attachment to reach the sustaining pedals of his piano. Their stories show the force of human genius in music.
PubMed: 38869229
DOI: 10.1177/00031348241259307 -
Cell Communication and Signaling : CCS Jun 2024Mesenchymal stem cells (MSCs) are widely used in the development of therapeutic tools in regenerative medicine. However, their quality decreases during in vitro...
BACKGROUND
Mesenchymal stem cells (MSCs) are widely used in the development of therapeutic tools in regenerative medicine. However, their quality decreases during in vitro expansion because of heterogeneity and acquired cellular senescence. We investigated the potential role of podoplanin (PDPN) in minimizing cellular senescence and maintaining the stemness of tonsil-derived MSCs (TMSCs).
METHODS
TMSCs were isolated from human tonsil tissues using an enzymatic method, expanded, and divided into two groups: early-passaged TMSCs, which were cultured for 3-7 passages, and late-passaged TMSCs, which were passaged more than 15 times. The TMSCs were evaluated for cellular senescence and MSC characteristics, and PDPN-positive and -negative cells were identified by fluorescence-activated cell sorting. In addition, MSC features were assessed in siRNA-mediated PDPN-depleted TMSCs.
RESULTS
TMSCs, when passaged more than 15 times and becoming senescent, exhibited reduced proliferative rates, telomere length, pluripotency marker (NANOG, OCT4, and SOX2) expression, and tri-lineage differentiation potential (adipogenesis, chondrogenesis, or osteogenesis) compared to cells passaged less than five times. Furthermore, PDPN protein levels significantly decreased in a passage-dependent manner. PDPN-positive cells maintained their stemness characteristics, such as MSC-specific surface antigen (CD14, CD34, CD45, CD73, CD90, and CD105) and pluripotency marker expression, and exhibited higher tri-lineage differentiation potential than PDPN-negative cells. SiRNA-mediated silencing of PDPN led to decreased cell-cycle progression, proliferation, and migration, indicating the significance of PDPN as a preliminary senescence-related factor. These reductions directly contributed to the induction of cellular senescence via p16/Rb pathway activation.
CONCLUSION
PDPN may serve as a novel biomarker to mitigate cellular senescence in the clinical application of MSCs.
Topics: Mesenchymal Stem Cells; Humans; Cellular Senescence; Membrane Glycoproteins; Cyclin-Dependent Kinase Inhibitor p16; Palatine Tonsil; Cell Differentiation; Cell Proliferation; Signal Transduction; Cells, Cultured
PubMed: 38867259
DOI: 10.1186/s12964-024-01705-8 -
Scientific Reports Jun 2024The aim of the present study was to examine the growth dynamics of the two ossification centers of the body of sphenoid bone in the human fetus, based on their linear,...
The aim of the present study was to examine the growth dynamics of the two ossification centers of the body of sphenoid bone in the human fetus, based on their linear, planar and volumetric parameters. The examinations were carried out on 37 human fetuses of both sexes aged 18-30 weeks of gestation, which had been preserved in 10% neutral formalin solution. Using CT, digital image analysis software, 3D reconstruction and statistical methods, we evaluated the size of the presphenoid and postsphenoid ossification centers. The presphenoid ossification center grew proportionately in sagittal diameter, projection surface area and volume, and logarithmically in transverse diameter. The postsphenoid ossification center increased logarithmically in sagittal diameter, transverse diameter and projection surface area, while its volumetric growth followed proportionately. The numerical findings of the presphenoid and postsphenoid ossification centers may be considered age-specific reference values of potential relevance in monitoring the normal fetal growth and screening for congenital disorders in the fetus. The obtained results may contribute to a better understanding of the growing fetal skeleton, bringing new numerical information regarding its diagnosis and development.
Topics: Humans; Sphenoid Bone; Female; Osteogenesis; Male; Fetus; Tomography, X-Ray Computed; Fetal Development; Imaging, Three-Dimensional; Gestational Age
PubMed: 38866900
DOI: 10.1038/s41598-024-64550-2 -
Medical Science Monitor : International... Jun 2024The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and...
The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Rongfeng Zhang, Jianwei Liu, Shengpeng Yu, Dong Sun, Xiaohua Wang, Jingshu Fu, Jie Shen, Zhao Xie. Osteoprotegerin (OPG) Promotes Recruitment of Endothelial Progenitor Cells (EPCs) via CXCR4 Signaling Pathway to Improve Bone Defect Repair. Med Sci Monit, 2019; 25: 5572-5579. DOI: 10.12659/MSM.916838.
Topics: Endothelial Progenitor Cells; Receptors, CXCR4; Osteoprotegerin; Signal Transduction; Animals; Bone Regeneration; Humans; Bone and Bones; Osteogenesis; Male; Mice; Wound Healing
PubMed: 38864115
DOI: 10.12659/MSM.945471 -
The Journal of International Medical... Jun 2024Pregnant women with severe osteogenesis imperfecta (OI) are uncommon, and there are limited data regarding anaesthesia for caesarean section in these high-risk...
Pregnant women with severe osteogenesis imperfecta (OI) are uncommon, and there are limited data regarding anaesthesia for caesarean section in these high-risk individuals. The presence of anatomical and physiological abnormalities can pose technical challenges for the anaesthetist. This report describes the successful implementation of epidural anaesthesia in a parturient with severe OI. To our knowledge, this is the first documented use of ultrasound-assisted neuraxial anaesthesia and wrist blood pressure monitoring in such patients undergoing caesarean section. Understanding the pathophysiological changes associated with OI is crucial for ensuring safe administration of anaesthesia to these women.
Topics: Humans; Osteogenesis Imperfecta; Female; Pregnancy; Cesarean Section; Adult; Pregnancy Complications; Anesthesia, Epidural; Anesthesia, Obstetrical; Anesthetists
PubMed: 38863132
DOI: 10.1177/03000605241260551 -
Aging Jun 2024The global prevalence of osteoporosis is being exacerbated by the increasing number of aging societies and longer life expectancies. In response, numerous drugs have...
The global prevalence of osteoporosis is being exacerbated by the increasing number of aging societies and longer life expectancies. In response, numerous drugs have been developed in recent years to mitigate bone resorption and enhance bone density. Nonetheless, the efficacy and safety of these pharmaceutical interventions remain constrained. Corylin (CL), a naturally occurring compound derived from the anti-osteoporosis plant L., has exhibited promising potential in impeding osteoclast differentiation. This study aims to evaluate the effect and molecular mechanisms of CL regulating osteoclast differentiation and its potential as a therapeutic agent for osteoporosis treatment . Our investigation revealed that CL effectively inhibits osteoclast formation and their bone resorption capacity by downregulating the transcription factors NFATc1 and c-fos, consequently resulting in the downregulation of genes associated with bone resorption. Furthermore, it has been observed that CL can effectively mitigate the migration and fusion of pre-osteoclast, while also attenuating the activation of mitochondrial mass and function. The results obtained from an study have demonstrated that CL is capable of attenuating the bone loss induced by ovariectomy (OVX). Based on these significant findings, it is proposed that CL exhibits considerable potential as a novel drug strategy for inhibiting osteoclast differentiation, thereby offering a promising approach for the treatment of osteoporosis.
Topics: Animals; Osteoclasts; Osteoporosis; Cell Differentiation; Mice; Bone Resorption; Female; Ovariectomy; NFATC Transcription Factors; RAW 264.7 Cells; Osteogenesis; Flavonoids
PubMed: 38862240
DOI: 10.18632/aging.205885 -
Frontiers in Medicine 2024Current evidences suggest that Proprotein Convertase Subtilisin/kexin Type 9 inhibitors (PCSK9i) exhibit a protective influence on acute coronary syndrome (ACS)....
BACKGROUND
Current evidences suggest that Proprotein Convertase Subtilisin/kexin Type 9 inhibitors (PCSK9i) exhibit a protective influence on acute coronary syndrome (ACS). Nevertheless, further investigation is required to comprehend the impact and mechanisms of these pharmaceutical agents on inflammatory factors and arterial stiffness (AS) in patients with ACS. Consequently, the objective of this study is to ascertain the influence of PCSK9i on arterial stiffness in ACS patients and elucidate the underlying mechanisms behind their actions.
METHODS
This study employed Mendelian randomization (MR) analysis to examine the association between genetic prediction of PCSK9 inhibition and arterial stiffness. Data of 71 patients with ACS were retrospectively collected, including PCSK9i group ( = 36, PCSK9 inhibitors combined with statins) and control group ( = 35, statins only). Blood lipid levels, inflammatory markers and pulse wave velocity (PWV) data were collected before treatment and at 1 and 6 months after treatment for analysis. Additionally, cell experiments were conducted to investigate the impact of PCSK9i on osteogenesis of vascular smooth muscle cells (VSMCs), utilizing western blot (WB), enzyme-linked immunosorbent assay (ELISA), and calcification index measurements.
RESULTS
The results of the MR analysis suggest that genetic prediction of PCSK9 inhibition has potential to reduce the PWV. Following treatment of statins combined with PCSK9 inhibitors for 1 and 6 months, the PCSK9i group exhibited significantly lower levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen (FIB) and procalcitonin (PCT) compared to the control group ( < 0.05). Additionally, PWV in the PCSK9i group demonstrated significant reduction after 6 months of treatment and was found to be associated with the circulating CRP level. In cell experiments, PCSK9i pretreatment ameliorated osteogenesis of VSMCs through reducing the deposition of calcium ions, alkaline phosphatase (ALP) activity, and expression of runt-related transcription factor 2 (RUNX2).
CONCLUSION
PCSK9i have potential to enhance arterial stiffness in ACS patients. Specifically, at the clinical level, this impact may be attributed to alterations in circulating CRP levels. At the cellular level, it is associated with the signaling pathway linked to RUNX2.
PubMed: 38860206
DOI: 10.3389/fmed.2024.1408760 -
Journal of Extracellular Vesicles Jun 2024Matrix vesicles (MVs) provide the initial site for amorphous hydroxyapatite (HA) formation within mineralizing osteoblasts. Although Na/Ca exchanger isoform-3 (NCX3,...
Matrix vesicles (MVs) provide the initial site for amorphous hydroxyapatite (HA) formation within mineralizing osteoblasts. Although Na/Ca exchanger isoform-3 (NCX3, SLC8A3) was presumed to function as major Ca transporter responsible for Ca extrusion out of osteoblast into the calcifying bone matrix, its presence and functional role in MVs have not been investigated. In this study, we investigated the involvement of NCX3 in MV-mediated mineralization process and its impact on bone formation. Using differentiated MC3T3-E1 cells, we demonstrated that NCX3 knockout in these cells resulted in a significant reduction of Ca deposition due to reduced Ca entry within the MVs, leading to impaired mineralization. Consequently, the capacity of MVs to promote extracellular HA formation was diminished. Moreover, primary osteoblast isolated from NCX3 deficient mice (NCX3) exhibits reduced mineralization efficacy without any effect on osteoclast activity. To validate this in vitro finding, μCT analysis revealed a substantial decrease in trabecular bone mineral density in both genders of NCX3 mice, thus supporting the critical role of NCX3 in facilitating Ca uptake into the MVs to initiate osteoblast-mediated mineralization. NCX3 expression was also found to be the target of downregulation by inflammatory mediators in vitro and in vivo. This newfound understanding of NCX3's functional role in MVs opens new avenues for therapeutic interventions aimed at enhancing bone mineralization and treating mineralization-related disorders.
Topics: Animals; Osteoblasts; Sodium-Calcium Exchanger; Mice; Calcium; Calcification, Physiologic; Mice, Knockout; Male; Osteogenesis; Cell Differentiation; Female; Extracellular Vesicles; Cell Line
PubMed: 38859730
DOI: 10.1002/jev2.12450 -
Plastic and Reconstructive Surgery.... Jun 2024Frontosphenoidal craniosynostosis (FSC) is a rare premature fusion of the frontosphenoidal suture that results in anterior plagiocephaly. When associated with severe...
Frontosphenoidal craniosynostosis (FSC) is a rare premature fusion of the frontosphenoidal suture that results in anterior plagiocephaly. When associated with severe cranial deformity, surgical treatment is beneficial. All previously reported cases of FSC correction have utilized fronto-orbital remodeling and advancement to achieve improved anatomy and increased intracranial volume. For patients with isolated synostosis deformities, we believe that distraction osteogenesis can be a viable option, with the additional benefit of quicker operating time, shorter hospital stays, and less irregularity in final head contour. This case illustrates the feasibility of using distraction osteogenesis in the management of FSC.
PubMed: 38855136
DOI: 10.1097/GOX.0000000000005893 -
Regenerative Biomaterials 2024The joint prosthesis plays a vital role in the outcome of total hip arthroplasty. The key factors that determine the performance of joint prostheses are the materials...
The joint prosthesis plays a vital role in the outcome of total hip arthroplasty. The key factors that determine the performance of joint prostheses are the materials used and the structural design of the prosthesis. This study aimed to fabricate a porous tantalum (Ta) hip prosthesis using selective laser melting (SLM) technology. The feasibility of SLM Ta use in hip prosthesis was verified by studying its chemical composition, metallographic structure and mechanical properties. experiments proved that SLM Ta exhibited better biological activities in promoting osteogenesis and inhibiting inflammation than SLM Ti6Al4V. Then, the topological optimization design of the femoral stem of the SLM Ta hip prosthesis was carried out by finite element simulation, and the fatigue performance of the optimized prosthesis was tested to verify the biomechanical safety of the prosthesis. A porous Ta acetabulum cup was also designed and fabricated using SLM. Its mechanical properties were then studied. Finally, clinical trials were conducted to verify the clinical efficacy of the SLM Ta hip prosthesis. The porous structure could reduce the weight of the prosthesis and stress shielding and avoid bone resorption around the prosthesis. In addition, anti-infection drugs can also be loaded into the pores for infection treatment. The acetabular cup can be custom-designed based on the severity of bone loss on the acetabular side, and the integrated acetabular cup can repair the acetabular bone defect while achieving the function of the acetabular cup.
PubMed: 38854680
DOI: 10.1093/rb/rbae057