RESUMO
We observed at our university-based imaging centers that when prostate-specific membrane antigen (PSMA) PET/CT became available for staging and restaging prostate cancer, the volume of bone scanning on patients with prostate cancer (BS-P) markedly decreased. We aimed to study use patterns of PSMA PET/CT and BS-P at our imaging centers during the 4-y period around U.S. Food and Drug Administration approval of PSMA PET/CT in December 2020. We tested the hypothesis that the rate of decline of BS-P accelerated after U.S. Food and Drug Administration approval, as physicians planned for use of PSMA PET/CT in their patients. Methods: Our clinical report system was searched for BS-P and PSMA PET/CT scans from January 2019 through June 2023. Numbers of scans were tabulated by quarter and year. Quantitative and statistical analyses were performed. Results: Annualized average monthly BS-P peaked at 53.7 scans/mo in 2021 and then decreased over time. There were 552 BS-Ps performed in 2019, 503 in 2020, 614 in 2021, 481 in 2022, and 152 in the first half of 2023. BS-P monthly averages declined by 22% from 2021 to 2022 and by 36% from 2022 to 2023, whereas monthly PSMA PET/CT scan averages increased by 1,416% from 2021 to 2022 and by 69% from 2022 to 2023. There was a significantly greater decline in BS-Ps from 2022 to 2023 than from 2021 to 2022 (36% vs. 22%, P < 0.0001). There were 30 PSMA PET/CT scans performed in 2021, 455 in 2022, and 384 in the first half of 2023. The greatest quarterly increase in these scans (400%) occurred at the outset of PSMA PET/CT implementation in quarter 4 of 2021. In quarter 2 of 2023, the percentage of total studies was higher for PSMA PET/CT than for BS-P (74% vs. 26%, P < 0.0001). Conclusion: At our university-based imaging centers, use of BS-P has declined in correlation with the timing of U.S. Food and Drug Administration approval and implementation of PSMA PET/CT. This study illustrates one instance of workflow changes that occur in the nuclear medicine clinic when new agents are introduced and affect clinical management options.
Assuntos
Antígenos de Superfície , Glutamato Carboxipeptidase II , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Humanos , Masculino , Antígenos de Superfície/metabolismo , Osso e Ossos/diagnóstico por imagem , Neoplasias Ósseas/diagnóstico por imagem , Glutamato Carboxipeptidase II/metabolismo , Hospitais Universitários , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/diagnóstico por imagemRESUMO
Over 50 billion cells undergo apoptosis each day in an adult human to maintain tissue homeostasis by eliminating damaged or unwanted cells. Apoptotic deficiency can lead to age-related diseases with reduced apoptotic metabolites. However, whether apoptotic metabolism regulates aging is unclear. Here, we show that aging mice and apoptosis-deficient MRL/lpr (B6.MRL-Faslpr/J) mice exhibit decreased apoptotic levels along with increased aging phenotypes in the skeletal bones, which can be rescued by the treatment with apoptosis inducer staurosporine (STS) and stem cell-derived apoptotic vesicles (apoVs). Moreover, embryonic stem cells (ESC)-apoVs can significantly reduce senescent hallmarks and mtDNA leakage to rejuvenate aging bone marrow mesenchymal stem cells (MSCs) and ameliorate senile osteoporosis when compared to MSC-apoVs. Mechanistically, ESC-apoVs use TCOF1 to upregulate mitochondrial protein transcription, resulting in FLVCR1-mediated mitochondrial functional homeostasis. Taken together, this study reveals a previously unknown role of apoptotic metabolites in ameliorating bone aging phenotypes and the unique role of TCOF1/FLVCR1 in maintaining mitochondrial homeostasis.
Assuntos
Envelhecimento , Apoptose , Homeostase , Células-Tronco Mesenquimais , Mitocôndrias , Animais , Humanos , Camundongos , Envelhecimento/metabolismo , Apoptose/efeitos dos fármacos , Osso e Ossos/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/genética , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos MRL lpr , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Osteoporose/metabolismo , Fenótipo , Estaurosporina/farmacologiaRESUMO
Introduction: Introduction: musculoskeletal health has become of increasing interest due to the ageing of the population and the increase in the prevalence of associated diseases. Objective: analyze scientific evidence on the role of nutrition and diet in maintaining muscle and bone health and preventing related diseases. Methods: review of the scientific literature on nutrition and diet in maintaining muscle and bone health. Results and discussion: dietary components such as protein, calcium, magnesium, vitamin D, C, K, B12, among others, have been positively associated with the maintenance of muscle and bone. The Mediterranean diet could slow the onset of sarcopenia and osteoporosis. Conclusion: nutrition is crucial for muscle and bone health.
Introducción: Introducción: la salud musculoesquelética ha adquirido un interés creciente debido al envejecimiento poblacional y al aumento de enfermedades asociadas. Objetivo: analizar la evidencia sobre el papel de la nutrición y la dieta en la salud muscular y ósea y la prevención de enfermedades asociadas. Métodos: revisión de la literatura científica sobre la nutrición y la dieta en el mantenimiento de una adecuada salud muscular y ósea. Resultados y discusión: componentes dietéticos como las proteínas, el calcio, el magnesio y las vitaminas D, C, K, B12, entre otros, se han asociado positivamente con el mantenimiento de la salud muscular y ósea. La dieta mediterránea podría ralentizar la aparición de la sarcopenia y la osteoporosis. Conclusión: la nutrición es crucial para la salud muscular y ósea.
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Osso e Ossos , Dieta , Sarcopenia , Humanos , Osso e Ossos/metabolismo , Osso e Ossos/fisiologia , Sarcopenia/prevenção & controle , Sarcopenia/dietoterapia , Dieta Mediterrânea , Osteoporose/prevenção & controle , Osteoporose/dietoterapia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologiaRESUMO
Evolutionary body size decrease has profound consequences for the morphology of an organism. In the evolution of the Characidae, the most species-rich family of Neotropical fishes, a prominent trend is the reduction of body size. The most typical effect is the simplification and reduction of morphological features through terminal deletion processes, resulting in the loss of skeletal elements and structures. To provide further information on the matter, we present a detailed description of the skeleton of Hyphessobrycon piabinhas, a poorly known, small representative of the largest genus of Characidae. We further discuss the identity and phylogenetic relationships of H. piabinhas. It belongs to the subfamily Stethaprioninae and exhibits considerable morphological similarity to other congeners from neighboring drainage systems. We identify several morphological simplifications in H. piabinhas and discuss them based on ontogenetic data available for Characiformes. These developmentally truncated elements are also present in many other small representatives of the family and seem to be among the first morphological modifications to occur in the context of body size reduction of Characidae. We argue that structural losses are not strictly correlated with sizes below 26 mm SL, although the most notable simplifications are typically observed in the miniatures.
Assuntos
Tamanho Corporal , Filogenia , Animais , Characidae/anatomia & histologia , Characidae/genética , Evolução Biológica , Osteologia , Osso e Ossos/anatomia & histologiaRESUMO
Bone morphogenetic protein-2 (BMP-2) has been commercially approved by the Food and Drug Administration for use in bone defects and diseases. BMP-2 promotes osteogenic differentiation of mesenchymal stem cells. In bone tissue engineering, BMP-2 incorporated into scaffolds can be used for stimulating bone regeneration in organoid construction, drug testing platforms, and bone transplants. However, the high dosage and uncontrollable release rate of BMP-2 challenge its clinical application, mainly due to the short circulation half-life of BMP-2, microbial contamination in bone extracellular matrix hydrogel, and the delivery method. Moreover, in clinical translation, the requirement of high doses of BMP-2 for efficacy poses challenges in cost and safety. Based on these, novel strategies should ensure that BMP-2 is delivered precisely to the desired location within the body, regulating the timing of BMP-2 release to coincide with the bone healing process, as well as release BMP-2 in a controlled manner to optimize its therapeutic effect and minimize side effects. This review highlights improvements in bone tissue engineering applying spatiotemporal and controlled BMP-2 delivery, including molecular engineering, biomaterial modification, and synergistic therapy, aiming to provide references for future research and clinical trials.
Assuntos
Proteína Morfogenética Óssea 2 , Osso e Ossos , Engenharia Tecidual , Proteína Morfogenética Óssea 2/metabolismo , Engenharia Tecidual/métodos , Humanos , Animais , Osso e Ossos/metabolismo , Regeneração Óssea , Alicerces Teciduais/química , OsteogêneseRESUMO
Diabetic neuropathy is one of the most common diabetes mellitus complications associated with mediocalcinosis of the lower extremities, a significant decrease in feet bone mineral density, and a high incidence of cardiovascular disease. In most cases, calcium-phosphorus metabolism changes occur in patients with diabetic neuroarthropathy, or Charcot foot, when we can observe feet local osteoporosis, which in 90% of cases associated with a vessel's calcification of the lower extremities in the majority of diabetes population. A large number of studies presented literature have demonstrated that patients with Charcot foot can have accelerated bone metabolism and increased bone resorption. Patients with Charcot foot often have crucial abnormalities in the calcium-phosphorus parameters, bone metabolism, and levels of vitamin D and its metabolites. In addition, the duration of diabetes mellitus, the degree of its compensation widely affects the development of its micro- and macrovascular complications, which could also accelerate the development of mineral and bone disorders in these types of patients. Multifactorial pathogenesis of these disorders complicates the management of patients with a long and complicated course of diabetes mellitus. This review discusses the peculiarities of vitamin D metabolism, the importance of timely diagnosis in phosphorus-calcium disorders, and the specifics of therapy in these patients. Special attention is paid to the timely diagnosis of the Charcot's foots acute stage based on the bone marrow edema by MRI evaluation and the possibility of reducing the immobilization period.
Assuntos
Artropatia Neurogênica , Pé Diabético , Humanos , Pé Diabético/metabolismo , Pé Diabético/patologia , Artropatia Neurogênica/metabolismo , Artropatia Neurogênica/patologia , Artropatia Neurogênica/etiologia , Vitamina D/metabolismo , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Fósforo/metabolismo , Cálcio/metabolismo , Densidade Óssea , Osteoporose/metabolismo , Osteoporose/etiologiaRESUMO
Among the most widely used methods for understanding human-horse relationships in the archaeological record is the identification of human skeletal pathologies associated with mounted horseback riding. In particular, archaeologists encountering specific bony changes to the hip, femur, and lower back often assert a causal link between these features and prolonged periods of mounted horseback riding. The identification of these features have recently been used to assert the early practice of mounted horseback riding among the Yamnaya culture of western Eurasia during the third and fourth millennium BCE. Here, we summarize the methodological hurdles and analytical risks of using this approach in the absence of valid comparative datasets and outline best practices for using human osteological data in the study of ancient animal transport.
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Arqueologia , Osso e Ossos , Humanos , Animais , Cavalos , Arqueologia/métodos , Osso e Ossos/fisiologia , História Antiga , EsqueletoRESUMO
Here we describe a dataset of freely available, readily processed, whole-body µCT-scans of 56 species (116 specimens) of Lake Malawi cichlid fishes that captures a considerable majority of the morphological variation present in this remarkable adaptive radiation. We contextualise the scanned specimens within a discussion of their respective ecomorphological groupings and suggest possible macroevolutionary studies that could be conducted with these data. In addition, we describe a methodology to efficiently µCT-scan (on average) 23 specimens per hour, limiting scanning time and alleviating the financial cost whilst maintaining high resolution. We demonstrate the utility of this method by reconstructing 3D models of multiple bones from multiple specimens within the dataset. We hope this dataset will enable further morphological study of this fascinating system and permit wider-scale comparisons with other cichlid adaptive radiations.
Assuntos
Ciclídeos , Lagos , Microtomografia por Raio-X , Animais , Ciclídeos/anatomia & histologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/anatomia & histologia , Malaui , Evolução BiológicaRESUMO
BACKGROUND: Bone regeneration is a well-regulated dynamic process, of which the prominent role of the immune system on bone homeostasis is more and more revealed by recent research. Before fully activation of the bone remodeling cells, the immune system needs to clean up the microenvironment in facilitating the bone repair initiation. Furthermore, this microenvironment must be maintained properly by various mechanisms over the entire bone regeneration process. OBJECTIVE: This review aims to summarize the role of the T-helper 17/Regulatory T cell (Th17/Treg) balance in bone cell remodeling and discuss the relevant progress in bone tissue engineering. RESULTS: The role of the immune response in the early stages of bone regeneration is crucial, especially the impact of the Th17/Treg balance on osteoclasts, mesenchymal stem cells (MSCs), and osteoblasts activity. By virtue of these knowledge advancements, innovative approaches in bone tissue engineering, such as nano-structures, hydrogel, and exosomes, are designed to influence the Th17/Treg balance and thereby augment bone repair and regeneration. CONCLUSION: Targeting the Th17/Treg balance is a promising innovative strategy for developing new treatments to enhance bone regeneration, thus offering potential breakthroughs in bone injury clinics.
Assuntos
Regeneração Óssea , Osso e Ossos , Linfócitos T Reguladores , Células Th17 , Engenharia Tecidual , Humanos , Linfócitos T Reguladores/imunologia , Engenharia Tecidual/métodos , Regeneração Óssea/imunologia , Animais , Células Th17/imunologia , Osso e Ossos/imunologia , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Remodelação Óssea/imunologia , Osteoblastos/imunologia , Osteoclastos/imunologia , Osteoclastos/metabolismoRESUMO
Background and aims: Reduced bone mineral density (BMD) and microarchitectural deterioration contribute to increased fracture risk. Although the effects of anti-fracture medications (AFMs) on BMD are well-documented, their impact on bone material properties (BMPs) remains poorly characterized. Accordingly, we conducted a systematic review and meta-analysis to evaluate the effects of AFMs on BMPs. Based on data availability, we further categorized AFMs into anti-resorptives, bisphosphonates alone, and strontium ranelate subgroups to perform additional analyses of BMPs in osteoporotic patients. Methods: We did a comprehensive search of three databases, namely, PubMed, Web of Science, and Google Scholar, using various permutation combinations, and used Comprehensive Meta-Analysis software to analyze the extracted data. Results: The 15 eligible studies (randomized and non-randomized) compared the following: (1) 301 AFM-treated patients with 225 on placebo; (2) 191 patients treated with anti-resorptives with 131 on placebo; (3) 86 bisphosphonate-treated patients with 66 on placebo; and (4) 84 strontium ranelate-treated patients with 70 on placebo. Pooled analysis showed that AFMs significantly decreased cortical bone crystallinity [standardized difference in means (SDM) -1.394] and collagen maturity [SDM -0.855], and collagen maturity in cancellous bone [SDM -0.631]. Additionally, anti-resorptives (bisphosphonates and denosumab) significantly increased crystallinity [SDM 0.387], mineral-matrix ratio [SDM 0.771], microhardness [SDM 0.858], and contact hardness [SDM 0.952] of cortical bone. Anti-resorptives increased mineral-matrix ratio [SDM 0.543] and microhardness [SDM 0.864] and decreased collagen maturity [SDM -0.539] in cancellous bone. Restricted analysis of only bisphosphonate-treated studies showed a significant decrease in collagen maturity [SDM -0.650] in cancellous bone and an increase in true hardness [SDM 1.277] in cortical bone. In strontium ranelate-treated patients, there was no difference in BMPs compared to placebo. Conclusion: Collectively, our study suggests that AFMs improve bone quality, which explains their anti-fracture ability that is not fully accounted for by increased BMD in osteoporosis patients.
Assuntos
Conservadores da Densidade Óssea , Densidade Óssea , Humanos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/farmacologia , Difosfonatos/uso terapêutico , Difosfonatos/farmacologia , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Tiofenos/uso terapêuticoRESUMO
Lead poisoning remains the leading cause of diagnosed death for critically endangered California condors, which are annually monitored for lead exposure via blood tests. Blood tests are generally reflective of acute lead exposure. Since condors are victims to both chronic and acute lead exposure, measuring bone, which in humans is reflective of years to decades worth of exposure, is a valuable biomarker. In this study, we measured bone Pb of the tibiotarsus of 64 condors in vivo using a portable x-ray fluorescence device. The average uncertainty for measurements, typically reflective of how effective the device performed, was found to be 3.8 ± 2.2 µg/g bone mineral. The average bone lead level was found to be 26.7 ± 24.5 µg/g bone mineral. Bone lead correlated significantly with a sum of all blood lead measures over the lifetime of each condor. In the future, bone lead can potentially be used to inform treatment planning and address the chronic health implications of lead in the species.
Assuntos
Osso e Ossos , Chumbo , Chumbo/sangue , Animais , Osso e Ossos/química , Intoxicação por Chumbo , California , Monitoramento Ambiental/métodos , Exposição AmbientalRESUMO
Bone homeostasis is a homeostasis process constructed by osteoblast bone formation and osteoclast bone resorption. Bone homeostasis imbalance and dysfunction are the basis for the development of various orthopedic diseases such as osteoporosis, osteoarthritis, and steroid-induced avascular necrosis of femoral head. Previous studies have demonstrated that ferroptosis can induce lipid peroxidation through the generation of reactive oxygen species, activate a number of signaling pathways, and participate in the regulation of osteoblast bone formation and osteoclast bone resorption, resulting in bone homeostasis imbalance, which is an important factor in the pathogenesis of many orthopedic diseases, but the mechanism of ferroptosis is still unknown. In recent years, it has been found that, in addition to iron metabolism and intracellular antioxidant system imbalance, organelle dysfunction is also a key factor affecting ferroptosis. This paper takes this as the starting point, reviews the latest literature reports at home and abroad, elaborates the pathogenesis and regulatory pathways of ferroptosis and the relationship between ferroptosis and various organelles, and summarizes the mechanism by which ferroptosis mediates bone homeostasis imbalance, with the aim of providing new directions for the research related to ferroptosis and new ideas for the prevention and treatment of bone and joint diseases.
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Ferroptose , Homeostase , Ferroptose/fisiologia , Humanos , Homeostase/fisiologia , Osso e Ossos/metabolismo , Transdução de Sinais/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Osteoblastos/metabolismo , Peroxidação de Lipídeos , Osteoporose/metabolismo , Osteoclastos/metabolismo , Doenças Ósseas/metabolismoRESUMO
Tissue engineering scaffolds are three-dimensional structures that provide an appropriate environment for cellular attachment, proliferation, and differentiation. Depending on their specific purpose, these scaffolds must possess distinct features, including appropriate mechanical properties, porosity, desired degradation rate, and cell compatibility. This investigation aimed to fabricate a new nanocomposite scaffold using a 3D printing technique composed of poly(ε-caprolactone) (PCL)/Gelatin (GEL)/ordered mesoporous calcium-magnesium silicate (om-CMS) particles. Different weight ratios of om-CMS were added and optimized, and a series of scaffolds were constructed for comparison purposes, including PCL 50%/Gel 50%, PCL 50%/Gel 45%/om-CMS%5, and PCL 50%/Gel 40%/om-CMS%10. The optimized weight ratio of om-CMS was 10% without leaving behind negative effects on the filaments' structure. The scaffolds' physical and chemical properties were assessed using various techniques, and their degradation rate, bioactivity potential, cell viability, attachment, and ALP activity were evaluated in vitro. The results demonstrated that the PCL 50%/Gel 40%/om-CMS10% scaffold had promising potential for further studies in bone tissue regeneration.
Assuntos
Regeneração Óssea , Gelatina , Nanocompostos , Poliésteres , Impressão Tridimensional , Silicatos , Engenharia Tecidual , Alicerces Teciduais , Gelatina/química , Alicerces Teciduais/química , Poliésteres/química , Nanocompostos/química , Regeneração Óssea/efeitos dos fármacos , Engenharia Tecidual/métodos , Silicatos/química , Porosidade , Sobrevivência Celular/efeitos dos fármacos , Silicatos de Magnésio/química , Teste de Materiais , Humanos , Proliferação de Células/efeitos dos fármacos , Compostos de Cálcio/química , Magnésio/química , Materiais Biocompatíveis/química , Osso e Ossos , Animais , Adesão Celular/efeitos dos fármacos , Cálcio/químicaRESUMO
This study looked at how desalinated seawater, which has low minerals and high boron, could affect bone health. Prior research suggests that low mineral water may harm bone health and boron could be beneficial, but the overall impact on bone health is still unclear. Eighty-nine-week-old male Balb/C mice were allocated into eight groups and administered either tap water or purified water with varying boron concentrations (0, 5, 40, and 200 mg/L). They were kept in an environment mimicking tropical conditions (35-40 °C, 70-80% humidity) and underwent daily treadmill exercise for 13 weeks. At the 14th week, serum, femora, and lumbar vertebrae were collected for mineral metabolism, bone biomarker, microstructure, and biomechanics evaluation. Boron exposure improved bone formation, microstructure, and biomechanics initially but the benefits weakened with higher levels of exposure (p < 0.05). Co-exposure to purified water elevated serum boron but weakened the promotion of boron on bone minerals and the bone benefits of boron compared to tap water (p < 0.05). Thus, when studying the health effects of boron in desalinated seawater, it is crucial to look at various health effects beyond bone health. Furthermore, it is important to consider the mineral composition of drinking water when using boron for bone health benefits.
Assuntos
Osso e Ossos , Boro , Camundongos Endogâmicos BALB C , Águas Minerais , Água do Mar , Animais , Boro/farmacologia , Masculino , Água do Mar/química , Camundongos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Densidade Óssea/efeitos dos fármacos , Água Potável , Biomarcadores/sangue , Vértebras Lombares/efeitos dos fármacos , Fêmur/efeitos dos fármacosRESUMO
Potassium is a cation involved in the resting phase of membrane potential. Diets rich in fresh fruit and vegetables, whole grains, dairy products, and coffee have high potassium content. The shift from a pre-agriculture diet to today's consumption has led to reduced potassium intake. Indeed, the Western diet pattern is characterized by a high daily intake of saturated fats, sugars, sodium, proteins from red meat, and refined carbohydrates with a low potassium intake. These reductions are also mirrored by high sodium intakes and a high consumption of acid-generating food, which promote a chronic state of low-grade metabolic acidosis. The low-grade metabolic acidosis is a cause of the bone-wasting effect. Therefore, a long-standing acidotic state brings into play the bone that contributes to the buffering process through an increase in osteoclastic resorption. In consideration of this background, we carried out a review that focused on the pathophysiological mechanisms of the relationship between dietary potassium intake and bone health, underlining the detrimental effects of the Western dietary patterns characterized by low potassium consumption.
Assuntos
Osso e Ossos , Potássio na Dieta , Humanos , Potássio na Dieta/administração & dosagem , Osso e Ossos/metabolismo , Dieta Ocidental/efeitos adversos , AcidoseRESUMO
Y chromosome short tandem repeats (Y-STRs) typing is a useful tool in scenarios such as mass graves analysis or disaster victim identification and has become a routine analysis in many laboratories. Not many comparisons have been performed with the currently available commercial kits, much less with degraded skeletal remains. This research aims to evaluate the performance of three commercial Y-STR kits: Yfiler™ Plus, PowerPlex® Y23, and Investigator® Argus Y-28 in 63 degraded skeletal remains from mass graves. PowerPlex® Y23 yields more reportable markers and twice the RFU on average, while Yfiler™ Plus and Investigator® Argus Y-28 exhibited a similar behaviour. Additionally, Argus Y-28, which has not been tested with this kind of samples in literature before, showed a good performance. Finally, a predictive model was attempted to be developed from quantification and autosomal STR data. However, no acceptable model could be obtained. Nevertheless, good Y-STR typing results may be expected if at least 50 pg DNA input is used or 13 autosomal markers were previously obtained.
Assuntos
Restos Mortais , Cromossomos Humanos Y , Impressões Digitais de DNA , Repetições de Microssatélites , Humanos , Impressões Digitais de DNA/métodos , Masculino , Reação em Cadeia da Polimerase , Degradação Necrótica do DNA , Osso e Ossos/químicaRESUMO
Objective Myeloma-related bone disease (MBD) is one of the most common complications of multiple myeloma (MM). This study aims to investigate the correlation between serum bone metabolism indexes (BMIs), the clinical characteristics and prognosis of newly diagnosed MM (NDMM) patients. METHODS: The serum BMIs of 148 patients with NDMM in a single hematological disease treatment center from April 2014 to December 2019 were analyzed retrospectively, including type I collagen amino terminal elongation peptide (PINP), ß-C-terminal telopeptide of type I collagen (ß-CTX) and N-terminal osteocalcin (N-MID). Other clinical indexes were simultaneously collected and the degree of bone damage in patients was evaluated. We explored the effect of serum BMIs on the prognosis and identified independent prognostic factors. Another 77 NDMM patients from April 2018 to February 2021 served as the validation cohort. RESULTS: The area under the curve (AUC) predicted by ß-C-terminal telopeptide of type I collagen (ß-CTX), type I collagen amino terminal elongation peptide (PINP), and N-terminal osteocalcin (N-MID) for overall survival (OS) were 0.708, 0.613, and 0.538, respectively. Patients with high serum levels had shorter OS (p < .001, p = .004, p = .027, respectively). Cox multivariate analysis indicated that serum ß- CTXãlactic dehydrogenaseãhemoglobin and the degree of bone injury were independent prognostic factors. A COX regression model was established with a C-index of 0.782 and validated with a C-index of 0.711. CONCLUSION: The serum BMIs are correlated with the patients' OS, and ß- CTX can be an independent prognostic factor.
Assuntos
Doenças Ósseas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Doenças Ósseas/etiologia , Doenças Ósseas/mortalidade , Doenças Ósseas/sangue , Doenças Ósseas/metabolismo , Estudos Retrospectivos , Colágeno Tipo I/sangue , Colágeno Tipo I/metabolismo , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Biomarcadores/sangue , Osteocalcina/sangue , Osteocalcina/metabolismo , Adulto , Idoso de 80 Anos ou mais , PeptídeosRESUMO
The treatment of irregular-shaped and critical-sized bone defects poses a clinical challenge. Deployable, self-fitting tissue scaffolds that can be implanted by minimally invasive procedures are a promising solution. Toward this, we fabricated NIR-responsive and programmable polylactide-co-trimethylene carbonate (PLMC) scaffolds nanoengineered with polydopamine nanoparticles (PDA) by extrusion-based three-dimensional (3D) printing. The 3D-printed scaffolds demonstrated excellent (>99%), fast (under 30 s), and tunable shape recovery under NIR irradiation. PLMC-PDA composites demonstrated significantly higher osteogenic potential in vitro as revealed by the significantly enhanced alkaline phosphatase (ALP) secretion and mineral deposition in contrast to neat PLMC. Intraoperative deployability and in vivo bone regeneration ability of PLMC-PDA composites were demonstrated, using self-fitting scaffolds in critical-sized cranial bone defects in rabbits. The 3D-printed scaffolds were deformed into compact shapes that could self-fit into the defect shape intraoperatively under low power intensity (0.76 W cm-2) NIR. At 6 and 12 weeks postsurgical implantation, near-complete bone regeneration was observed in PLMC-PDA composites, unlike neat PLMC through microcomputed tomography (micro-CT) analysis. The potential clinical utility of the 3D-printed composites to secure complex defects was confirmed through self-fitting of the scaffolds into irregular defects in ex vivo models of rabbit tibia, mandible, and tooth models. Taken together, the composite scaffolds fabricated here offer an innovative strategy for minimally invasive deployment to fit irregular and complex tissue defects for bone tissue regeneration.
Assuntos
Regeneração Óssea , Indóis , Osteogênese , Polímeros , Impressão Tridimensional , Alicerces Teciduais , Animais , Alicerces Teciduais/química , Coelhos , Regeneração Óssea/efeitos dos fármacos , Polímeros/química , Indóis/química , Osteogênese/efeitos dos fármacos , Poliésteres/química , Nanopartículas/química , Engenharia Tecidual , Dioxanos/química , Raios Infravermelhos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologiaRESUMO
OBJECTIVE: The study will be to observe the effect of Sodium butyrate (NaB) on bone loss in lipopolysaccharide (LPS)-treated rats. METHODS: In the rat model, we observed that changes in the expression of oxidative stress regulators, inflammatory markers and target genes were measured by immunofluorescence and RT-PCR after treatment. Changes in viability and osteogenesis of MC3T3-E1, osteoclast differentiation in RAW264.7 cells in the presence of LPS were evaluated using CCK-8, ALP staining, RES staining, and TRAP staining. RESULTS: In vitro experiments have shown that LPS-induced inhibition of JC-1, SIRT1, GPX1 and SOD2 is associated with increased levels of inflammation and oxidative stress. In addition, NaB has been found to suppress oxidative stress, inflammation and Mito SOX, promote osteogenic differentiation, and inhibit osteoclast differentiation. In addition, NaB significantly promoted SITR1 expression, repaired impaired bone metabolism, and improved bone strength and bone mineral density. CONCLUSION: Given all this experimental evidence, the results strongly suggest that NaB can restore osteogenic activity in the presence of LPS by reducing intracellular ROS, inhibiting osteoclast differentiation and reducing bone loss in LPS-treated rat models.
Assuntos
Ácido Butírico , Inflamação , Lipopolissacarídeos , Estresse Oxidativo , Animais , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ácido Butírico/farmacologia , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Camundongos , Células RAW 264.7 , Osteogênese/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Masculino , Ratos Sprague-Dawley , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismoRESUMO
The field of bone tissue engineering (BTE) has witnessed a revolutionary breakthrough with the advent of three-dimensional (3D) bioprinting technology, which is considered an ideal choice for constructing scaffolds for bone regeneration. The key to realizing scaffold biofunctions is the selection and design of an appropriate bioink, and existing bioinks have significant limitations. In this study, a composite bioink based on natural polymers (gelatin and alginate) and liver decellularized extracellular matrix (LdECM) was developed and used to fabricate scaffolds for BTE using 3D bioprinting. Through in vitro studies, the concentration of LdECM incorporated into the bioink was optimized to achieve printability and stability and to improve the proliferation and osteogenic differentiation of loaded rat bone mesenchymal stem cells (rBMSCs). Furthermore, in vivo experiments were conducted using a Sprague Dawley rat model of critical-sized calvarial defects. The proposed rBMSC-laden LdECM-gelatin-alginate scaffold, bioprinted layer-by-layer, was implanted in the rat calvarial defect and the development of new bone growth was studied for four weeks. The findings showed that the proposed bioactive scaffolds facilitated angiogenesis and osteogenesis at the defect site. The findings of this study suggest that the developed rBMSC-laden LdECM-gelatin-alginate bioink has great potential for clinical translation and application in solving bone regeneration problems.