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ABSTRACT: A 49-year-old woman patient with thyroid cancer accepted thyroidectomy and parathyroid transplantation. One month later, localized 131I uptake in the deltoid muscle bilaterally was detected by 131I whole-body imaging performed in 2 days after 131I administration.
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Ganoderic Acid A (GAA) has demonstrated beneficial effects in anti-inflammatory and anti-oxidative stress studies. However, it remains unknown whether GAA exerts positive impacts on bone loss induced by lipopolysaccharide (LPS). This study aims to investigate the influence of GAA on bone loss in LPS-treated rats. The study assesses changes in the viability and osteogenic potential of MC3T3-E1 cells, as well as osteoclast differentiation in RAW264.7 cells in the presence of LPS using CCK-8, ALP staining, AR staining, and Tartrate-resistant acid phosphatase (TRAP) staining. In vitro experiments indicate that LPS-induced inhibition of osteoclasts (OC) and Superoxide Dismutase 2 (SOD2) correlates with heightened levels of inflammation and oxidative stress. Furthermore, GAA has displayed the ability to alleviate oxidative stress and inflammation, enhance osteogenic differentiation, and suppress osteoclast differentiation. Animal experiment also proves that GAA notably upregulates SOD2 expression and downregulates TNF-α expression, leading to the restoration of impaired bone metabolism, improved bone strength, and increased bone mineral density. The collective experimental findings strongly suggest that GAA can enhance osteogenic activity in the presence of LPS by reducing inflammation and oxidative stress, hindering osteoclast differentiation, and mitigating bone loss in LPS-treated rat models.
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Diferenciación Celular , Ácidos Heptanoicos , Inflamación , Lanosterol , Lipopolisacáridos , Osteoclastos , Osteogénesis , Estrés Oxidativo , Ratas Sprague-Dawley , Superóxido Dismutasa , Animales , Lipopolisacáridos/farmacología , Estrés Oxidativo/efectos de los fármacos , Masculino , Ratones , Ratas , Células RAW 264.7 , Superóxido Dismutasa/metabolismo , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Diferenciación Celular/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Lanosterol/análogos & derivados , Lanosterol/farmacología , Lanosterol/uso terapéutico , Ácidos Heptanoicos/farmacología , Ácidos Heptanoicos/uso terapéutico , Densidad Ósea/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Resorción Ósea/prevención & control , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/metabolismoRESUMEN
OBJECTIVE: There is a dearth of comprehensive research on the stability of the spinal biomechanical structure when combining Oblique Lumbar Interbody Fusion (OLIF) with internal fixation methods. Hence, we have devised this experiment to meticulously examine and analyze the biomechanical changes that arise from combining OLIF surgery with different internal fixation techniques in patients diagnosed with degenerative lumbar spondylolisthesis. METHODS: Seven validated finite element models were reconstructed based on computed tomography scan images of the L3-L5 segment. These models included the intact model, a stand-alone (S-A) OLIF model, a lateral screw rod (LSR) OLIF model, a bilateral pedicle screw (BPS) OLIF model, an unilateral pedicle screw (UPS) OLIF model, a bilateral CBT (BCBT) OLIF model, and an unilateral CBT(UCBT) OLIF model. The range of motion (ROM), as well as stress levels in the cage, L4 lower endplate, L5 upper endplate, and fixation constructs were assessed across these different model configurations. RESULTS: S-A model had the highest average ROM of six motion modes, followed by LSR, UPS, UCBT, BPS and BCBT. The BCBT model had a relatively lower cage stress than the others. The maximum peak von Mises stress of the fixation constructs was found in the LSR model. The maximum peak von Mises stress of L4 lower endplate was found in the S-A model. The peak von Mises stress on the L4 lower endplate of the rest surgical models showed no significant difference. The maximum peak von Mises stress of the L5 upper endplate was found in the S-A model. The minimum peak von Mises stress of the L5 upper endplate was found in the BCBT model. No significant difference was found for the peak von Mises stress of the L5 upper endplate among LSR, BPS, UPS and UCBT models. CONCLUSION: Among the six different fixation techniques, BCBT exhibited superior biomechanical stability and minimal stress on the cage-endplate interface. It was followed by BPS, UCBT, UPS, and LSR in terms of effectiveness. Conversely, S-A OLIF demonstrated the least stability and resulted in increased stress on both the cage and endplates. Combining OLIF with BCBT fixation technique enhanced biomechanical stability compared to BPS and presented as a less invasive alternative treatment for patients with degenerative lumbar spondylolisthesis.
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Análisis de Elementos Finitos , Vértebras Lumbares , Rango del Movimiento Articular , Fusión Vertebral , Espondilolistesis , Humanos , Fusión Vertebral/métodos , Fusión Vertebral/instrumentación , Espondilolistesis/cirugía , Espondilolistesis/diagnóstico por imagen , Espondilolistesis/fisiopatología , Vértebras Lumbares/cirugía , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/fisiopatología , Fenómenos Biomecánicos/fisiología , Tornillos Pediculares , Masculino , Tomografía Computarizada por Rayos X , Persona de Mediana EdadRESUMEN
The accumulating evidence has made it clear that iron overload is a crucial mechanism in bone loss. Protocatechualdehyde (PCA) has also been used to prevent osteoporosis in recent years. Whether PCA can reverse the harmful effects of iron overload on bone mass in aged rats is still unknown. Therefore, this study aimed to assess the role of PCA in iron overload-induced bone loss in senile rats. In the aged rat model, we observed that iron overload affects bone metabolism and bone remodeling, manifested by bone loss and decreased bone mineral density. The administration of PCA effectively mitigated the detrimental effects caused by iron overload, and concomitant reduction in MDA serum levels and elevation of SOD were noted. In addition, PCA-treated rats were observed to have significantly increased bone mass and elevated expression of SIRT3ï¼BMP2ï¼SOD2 and reduced expression of TNF-α in bone tissue. We also observed that PCA was able to reduce oxidative stress and inflammation and restore the imbalance in bone metabolism. When MC3T3-E1 and RAW264.7 cells induced osteoblast and osteoclasts differentiation, PCA intervention could significantly recover the restriction of osteogenic differentiation and up-regulation of osteoclast differentiation treated by iron overload. Further, by detecting changes in ROS, SOD, MDA, expression of SIRT3 and mitochondrial membrane potentials, we confirm that the damage caused to cells by iron overload is associated with decreased SIRT3 activity, and that 3-TYP have similar effects on oxidative stress caused by FAC. In conclusion, PCA can resist iron overload-induced bone damage by improving SIRT3 activity, anti-inflammatory and anti-oxidative stress.
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A longstanding urban sociological literature emphasizes the geographic isolation of city dwellers in residence and everyday routines, expecting exposures to neighborhood racial and socio-economic structure driven principally by city-wide segregation and the role of proximity and homophily in mobility. The compelled mobility approach emphasizes the uneven distribution of organizational and institutional resources across urban space, expecting residents of poor Black-segregated neighborhoods to exhibit non-trivial levels of everyday exposure to White, non-poor areas for resource seeking. We use two sets of location data in the hypersegregated Chicago metro to examine these two approaches: Global Positioning System (GPS) location tracking on a sample of older adults from the Chicago Health and Activity Space in Real-Time (CHART) study and travel diaries on a sample of younger adults by the Chicago Metropolitan Agency for Planning (CMAP). We introduce a novel and flexible individual-level method for assessing activity space exposures that accounts for the spatially proximate environment around home. Analyses reveal that activity space contexts mimic the racial/ethnic and socio-economic landscape of respondents' broad residential environment. However, after residential-based adjustment, Black younger (CMAP) adults from poor Black neighborhoods are disproportionately exposed to Whiter, less Black but less non-poor neighborhoods. Older (CHART) adult activity spaces align more closely with their residential areas; however, activity spaces of poor-Black-neighborhood-residing CHART Blacks are systematically poorer and, less consistently, more Black and less White after local area adjustment. Implications for understanding contextual exposures on well-being and the potential for age or cohort differences in isolation are discussed.
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Thermally-induced dehydrogenative coupling of polyphenylenes on metal surfaces is an important technique to synthesize ð-conjugated carbon nanostructures with atomic precision. However, this protocol has rarely been utilized to fabricate structurally defined carbon nanosheets composed of sp- and sp2-hybridized carbon atoms. Here, we present the synthesis of butadiyne-linked hexabenzocoronenes (HBCs) on Au(111) surfaces as core-expanded graphdiynes. The reaction started from hexa(4-ethylphenyl)benzene, which undergoes dehydrogenation toward hexa(4-vinylphenyl)benzene, followed by planarization to hexabenzocoronene, coupling between the vinyl groups, and further dehydrogenation. In addition to butadiyne linkages, benzene groups were also found as another type of linker. The reaction sequences were monitored by scanning tunneling microscopy and bond-resolved non-contact atomic force microscopy, which disclose the structures of intermediates and final products. In combination with density functional theory simulations, the key steps from ethyl substituents to butadiyne and benzene linkers were elucidated. This is a new on-surface synthesis of core-expanded graphdiynes with unprecedented electronic properties.
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BACKGROUND: Recent studies have shown the potential of fibroblast activating protein inhibitor (FAPI) PET imaging for pancreatic cancer assessment. PURPOSE: This article is dedicated to comparing the diagnostic efficacy of FAPI PET and [18F]fluorodeoxyglucose (FDG) PET in the evaluation of primary tumors, lymph nodes, and distant metastases in pancreatic cancer. METHODS: In this review, we conducted a systematic search of studies published in PubMed and Web of Science databases up to September 18, 2023. All included studies used radionuclide labeled FAPI and FDG as PET diagnostic tracers to evaluate their applicability in patients with pancreatic cancer. RESULTS: The FAPI PET imaging group showed significantly higher sensitivity in the detection of primary lesions (1.000, [95% CI: 0.999-1.000]), lymph node metastases (0.624 [95% CI: 0.391-0.834]) and distant metastatic (0.965 [95% CI: 0.804-1.000]) in pancreatic cancer compared to the FDG PET imaging group (0.889 [95% CI: 0.788-0.966], 0.373 [95% CI: 0.163-0.606] and 0.889 [95% CI: 0.689-0.999], respectively). Furthermore, the maximum standardized uptake value (SUVmax) in FAPI PET imaging is significantly higher than that in FDG imaging for primary lesions (mean difference (MD) = 7.51, 95% CI: 5.34-9.67). CONCLUSION: Compared with [18F]FDG PET/CT, FAPI PET imaging showed higher sensitivity, SUVmax. This method can be effectively utilized for the evaluation of pancreatic cancer. CLINICAL RELEVANCE STATEMENT: Fibroblast activating protein inhibitor PET may be a better alternative to [18F]FDG in evaluating primary pancreatic cancer, lymph node metastases, and distant metastases. KEY POINTS: Fibroblast activating protein inhibitor (FAPI) PET is compared with FDG PET for evaluating pancreatic cancer. Multiple radiolabeled FAPI variants have shown promising results in the diagnosis of pancreatic cancer. FAPI PET imaging effectively helps clinicians diagnose and stage pancreatic cancer.
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OBJECTIVE: The aim of this study was to design a novel lumbar cortical bone trajectory (CBT) penetrating the anterior, middle, and posterior vertebral area using imaging; measure the relevant parameters to find theoretical parameters and screw placement possibilities; and investigate the optimal implantation trajectory of the CBT in patients with osteoporosis. METHODS: Three types of CBTs with appropriate lengths were selected to simulate screw placement using Mimics software. These CBTs were classified as the leading tip of the trajectory pointing to the posterior quarter area (original CBT [CBT-O]) and middle (novel CBT A [CBT-A]) and anterior quarter (novel CBT B [CBT-B]) of the superior endplate. The authors then measured the maximum screw diameter (MSD) and length (MSL), cephalad (CA) and lateral (LA) angles, and bone mineral density (Hounsfield unit [HU] values) of the planned novel 3-column CBT screw placements. The differences in the parameters of the novel CBTs, the percentages of successfully planned CBT screws, and the factors that influenced the successful planning of 3-column CBT screws were analyzed. RESULTS: Three-column CBT screws were successfully designed in all segments of the lumbar spine. The success rate of the 3-column CBT planned screws was 72.25% (83.25% for CBT-A and 61.25% for CBT-B). From the CBT-O type, to the CBT-A type, to the CBT-B type, the LA, CA, and MSD of the novel CBT screws decreased with increasing trajectory length. The HU values of the three types of trajectories were all significantly higher than that of the traditional pedicle screw trajectory (p < 0.001). The main factor affecting successful planning of the 3-column CBT screw was pedicle width. CONCLUSIONS: Moderating adjustment of the original screw parameters by reducing LAs and CAs to penetrate the anterior, middle, and posterior columns of the vertebral body using the 3-column CBT screw is feasible, especially in the lower lumbar spine.
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Hueso Cortical , Vértebras Lumbares , Humanos , Vértebras Lumbares/cirugía , Vértebras Lumbares/diagnóstico por imagen , Hueso Cortical/cirugía , Hueso Cortical/diagnóstico por imagen , Anciano , Femenino , Masculino , Persona de Mediana Edad , Osteoporosis/cirugía , Osteoporosis/diagnóstico por imagen , Densidad Ósea/fisiología , Tornillos Óseos , Tomografía Computarizada por Rayos X , Fusión Vertebral/métodos , Fusión Vertebral/instrumentaciónRESUMEN
N6-Methyladenosine (m6A) is one of the most abundant modifications of eukaryotic mRNA, but its comprehensive biological functionality remains further exploration. In this study, we identified and characterized a new flowering-promoting gene, EARLY HEADING DATE6 (EHD6), in rice. EHD6 encodes an RNA recognition motif (RRM)-containing RNA binding protein that is localized in the non-membranous cytoplasm ribonucleoprotein (RNP) granules and can bind both m6A-modified RNA and unmodified RNA indiscriminately. We found that EHD6 can physically interact with YTH07, a YTH (YT521-B homology) domain-containing m6A reader. We showed that their interaction enhances the binding of an m6A-modified RNA and triggers relocation of a portion of YTH07 from the cytoplasm into RNP granules through phase-separated condensation. Within these condensates, the mRNA of a rice flowering repressor, CONSTANS-like 4 (OsCOL4), becomes sequestered, leading to a reduction in its protein abundance and thus accelerated flowering through the Early heading date 1 pathway. Taken together, these results not only shed new light on the molecular mechanism of efficient m6A recognition by the collaboration between an RNA binding protein and YTH family m6A reader, but also uncover the potential for m6A-mediated translation regulation through phase-separated ribonucleoprotein condensation in rice.
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Flores , Regulación de la Expresión Génica de las Plantas , Oryza , Proteínas de Plantas , ARN Mensajero , Proteínas de Unión al ARN , Ribonucleoproteínas , Oryza/metabolismo , Oryza/genética , Oryza/crecimiento & desarrollo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Flores/metabolismo , Flores/crecimiento & desarrollo , Flores/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , ARN Mensajero/metabolismo , ARN Mensajero/genética , Ribonucleoproteínas/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismoRESUMEN
OBJECTIVES: To identify hub genes and biological processes of propofol-induced neurotoxicity and promote the development of pediatric anesthesiology. METHODS: We downloaded the GSE106799 dataset from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened, then Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Gene Set Enrichment analyses were performed on all DEGs. We identified potential ferroptosis genes in the pathogenesis of propofol-induced neurotoxicity. A key module was obtained after performing weighted gene co-expression network analysis (WGCNA) on the GSE106799 dataset. Hub genes were identified after the least absolute shrinkage and selection operator (LASSO) regression analysis of the intersection of DEGs and genes from the key module. We established a competing endogenous RNA network and predicted potential drugs according to the hub genes. Total RNA and proteins were extracted for real-time quantitative polymerase chain reaction and Western blotting, respectively. RESULTS: A total of 112 DEGs, including 76 upregulated and 36 downregulated ones were screened out. Propofol-induced neurotoxicity involved processes such as nervous system development, activation of JAK/STAT and MAPK signaling pathways, vascular regeneration, and oxidative stress. The results of WGCNA suggested that the tan module was the most strongly associated with propofol-induced neurotoxicity. We identified 4 hub genes (EGR4, HAO1, ITK and GM14446) after LASSO regression analysis. Animal experiments demonstrated that propofol caused overexpression of the protein levels of HAO1, ITK and inï¬ammatory factors in the brain, as well as the mRNA levels of HAO1, ITK and GM14446. Propofol inhibited expression of EGR4 at mRNA and protein levels. CONCLUSIONS: Previous studies have demonstrated that EGR4, HAO1, ITK and GM14446 play a role in intellectual development, neuroinflammation and neuronal differentiation. These hub genes may help us to find new preventive and therapeutic targets for propofol-induced neurotoxicity.
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STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The study aimed to compare the radiological parameters, clinical outcomes, and long-term effects of the posterior osteosynthesis with polyaxial screw-rod system and the monoaxial screw-rod system in the treatment of unstable atlas fractures. METHODS: We retrospectively analyzed the clinical data of 33 patients with posterior ORIF for unstable atlas fractures in our hospital from August 2013 to June 2020, with a minimum of 3 years of follow-up. Polyaxial screws (group A) were used in 12 patients and monoaxial screws (group B) in 21 patients. Perioperative data, radiological parameters, and clinical outcomes were collected and compared between the 2 surgical approaches. RESULTS: The operative time, blood loss, time of screw-rod system placement, and hospital stay were significantly lower in group A than in group B. At the last follow-up, the visual analog scale (VAS) score and anterior arch reduction rate of the atlas in group A were lower than those in group B, while the lateral mass displacement (LMD) in group A was higher than that in group B. There was no significant difference between Group A and Group B in terms of the anterior atlantodental interval (AADI), posterior arch reduction rate of the atlas, range of motion (ROM), and neck disability index (NDI). CONCLUSIONS: Monoaxial screws can achieve better reduction results for unstable atlas fractures, especially for the anterior arch of atlas. However, the surgical operation of monoaxial screws is more complicated than that of polyaxial screws and has more complications. Appropriate implants should be selected for the treatment of unstable atlas fractures based on the type of atlas fracture, the experience of surgeons, and the demands of patients.
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OBJECTIVES: The study aimed to assess the role of Astaxanthin (ATX) in palmitic acid(PA) -induced bone loss in Ovariectomized(OVX) rats. METHODS: In the OVX rat model, we observed that PA affects bone metabolism and accelerates bone loss. Additionally, treatment with ATX was able to suppress the deleterious effects of PA and a simultaneous decrease in serum MDA levels and an increase in SOD was observed. RESULTS: In addition, rats treated with ATX were observed to have significantly increased bone mass and elevated activity of SIRT1 and SOD2 in bone tissue. When MC3T3-E1 and RAW264.7 cells induced osteoblast and osteoclast differentiation, the ATX intervention was able to significantly restore the restriction of osteogenic differentiation and the up-regulation of osteoclast differentiation with PA therapy. Furthermore, we confirm that PA damage to cells is caused by increased oxidative stress, and that ATX can target and modulate the activity of SIRT1 to regulate the levels of oxidative stress in cells. CONCLUSION: Summarizing, ATX may inhibit PA-induced bone loss through its antioxidant properties via the SIRT1 signaling pathway.
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Osteoporosis , Ratas , Animales , Osteoporosis/tratamiento farmacológico , Osteoporosis/prevención & control , Osteogénesis , Ácido Palmítico/toxicidad , Sirtuina 1 , Diferenciación Celular , Estrés Oxidativo , XantófilasRESUMEN
OBJECTIVES: There has been developed a clinical dynamic total-body 68Ga-DOTATATE PET/CT imaging protocol that allows quantitative imaging of net influx rate (Ki). Using qualitative and quantitative analyses of clinical studies, this retrospective study aims to assess whether parametric Ki images improve lesion detectability. METHODS: Using a 194-cm axial field-of-view PET/CT scanner, 52 patients with neuroendocrine tumors underwent a 60-min dynamic total-body 68Ga-DOTATATE scan. Parametric Ki images and static standardized uptake value (SUV) images were generated. In addition to visual inspection of both sets of images, a quantitative analysis of 249 individual lesions was conducted using the target-to-background (TBR) metric. RESULTS: There were 52 patients who underwent dynamic total-body 68Ga-DOTATATE PET/CT scans. A total of 249 lesions were evaluated, of which 66 lesions were biopsy-proven and 183 lesions were unproven. Ki images produced two fewer false positives than the SUV images. Overall, our results from 66 proven NET lesions suggested similar sensitivity (98.5%) but improved accuracy (from 95.6 to 97.1%) and potentially enhanced specificity with Ki over SUV imaging. Besides, there was no difference in the number of pathological lesions identified visually in both images. However, Ki TBR was significantly higher than SUV TBR quantitatively (P < 0.001). CONCLUSIONS: Patlak Ki imaging provides nuclear physicians with a PET image with higher tumor contrast which may enhance confidence in diagnosis with possibly reduced false positive results, albeit an equivalent detectability, compared to static SUV image.
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Tumores Neuroendocrinos , Compuestos Organometálicos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Adulto , Transporte Biológico , Anciano de 80 o más Años , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
ABSTRACT: Two children with neuroblastoma underwent tumor resection and postoperative chemotherapy. After treatment, they participated in a clinical trial and received 18 F-MFBG and 18 F-FDG PET/CT examinations. Although similar lesions were found in the 2 examinations, the uptake pattern was different. The lymph nodes and bone lesions had intense 18 F-MFBG activity, whereas 18 F-FDG uptake was not very impressive. The uptake of bone marrow by 18 F-MFBG was significantly stronger than that by 18 F-FDG. This case emphasizes that 18 F-MFBG PET/CT is superior to 18 F-FDG PET/CT in detecting the metastases of neuroblastoma.
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Fluorodesoxiglucosa F18 , Metástasis de la Neoplasia , Neuroblastoma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/patología , Masculino , Femenino , Tomografía Computarizada por Rayos X , Preescolar , NiñoRESUMEN
PURPOSE: This study aimed to explore the feasibility of [68 Ga]pentixafor positron emission tomography/computed tomography (PET/CT) in patients with nasopharyngeal carcinoma (NPC). PROCEDURES: This prospective study included patients with NPC who underwent [68 Ga]pentixafor PET/CT and 2-[18F]fuoro-2-deoxy-D-glucose ([18F]FDG) PET/CT within one week between November 2022 and March 2023. The [68 Ga]pentixafor and [18F]FDG uptakes in primary and metastatic lesions were measured and compared. RESULTS: Twenty-five participants (21 patients for initial stage and four patients for recurrence detection) were enrolled in our study. The participants underwent [18F]FDG PET/CT and [68 Ga]pentixafor PET/CT. [68 Ga]pentixafor PET/CT had the same detection rate as [18F]FDG for primary tumor (96% vs. 96%). The [68 Ga]pentixafor maximum standard uptake value (SUVmax) and target-to-background ratio (TBR) of primary tumors were lower than those of [18F]FDG (SUVmax: 8.13 ± 2.78 vs. 14.25 ± 6.45; P < 0.01; TBR: 5.17 ± 2.14 vs. 9.81 ± 5.30, P < 0.01). The difference between tumor volume of [68 Ga]pentixafor (TVpentixafor) and tumor volume of [18F]FDG (TVFDG) showed no significance (median: 16.01 vs. 9.56, P = 0.332). In the detection of suspected metastatic cervical lymph nodes (CLNs), [68 Ga]pentixafor PET possessed a lower SUVmax than [18F]FDG PET/CT (SUVmax: 6.86 ± 2.63 vs. 10.39 ± 5.28, P < 0.01), but there was no significant difference in the detection rate between [68 Ga]pentixafor and [18F]FDG PET/CT (96 vs. 98, P = 0.613). CONCLUSIONS: [68 Ga]pentixafor is a promising imaging tracer for detecting primary and metastatic NPC. [68 Ga]pentixafor PET/CT is comparable to [18F]FDG PET/CT in the detection rate of primary tumors and metastatic cervical lymph nodes in nasopharyngeal carcinoma, but [68 Ga]pentixafor uptake was heterogeneous. [68 Ga]pentixafor PET/CT may help select patients most likely to benefit from CXCR4-directed endoradiotherapy. CLINICAL TRIAL REGISTRATION NO: ChiCTR2200065902.
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Fluorodesoxiglucosa F18 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Péptidos Cíclicos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18/química , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/patología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Péptidos Cíclicos/química , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/patología , Anciano , Complejos de Coordinación/química , Estudios ProspectivosRESUMEN
Recently, more and more studies have shown that guanylate cyclase, an enzyme that synthesizes cyclic guanosine monophosphate (cGMP), plays an important role in bone metabolism. Vericiguat (VIT), a novel oral soluble guanylate cyclase stimulator, directly generates cyclic guanosine monophosphate and reduce the death incidence from cardio-vascular causes or hospitalization. Recent studies have shown beneficial effects of VIT in animal models of osteoporosis, but very little is currently known about the effects of VIT on bone defects in the osteoporotic states. Therefore, in this study, ß-tricalcium phosphate (ß-TCP) was used as a carrier to explore the effect of local VIT administration on the repair of femoral metaphyseal bone defects in ovariectomized (OVX) rats. When MC3T3-E1 was cultured in the presence of H2H2, VIT, similar to Melatonin (MT), therapy could increase the matrix mineralization and ALP, SOD2, SIRT1, and OPG expression, reduce ROS and Mito SOX production, RANKL expression, Promote the recovery of mitochondrial membrane potential. In the OVX rat model, VIT increases the osteogenic effect of ß-TCP and better results were obtained at a dose of 5 mg. Local use of VIT can inhibit increased OC, BMP2 and RUNX2 expressions in bone tissue, while decreased SOST and TRAP expressions by RT-PCR and immunohistochemistry. Thereby, VIT stimulates bone regeneration and is a promising candidate for promoting bone repair in osteoporosis.
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Fosfatos de Calcio , Osteogénesis , Ratas Sprague-Dawley , Animales , Osteogénesis/efectos de los fármacos , Femenino , Ratones , Fosfatos de Calcio/química , Ratas , Ovariectomía , Línea Celular , Osteoporosis/tratamiento farmacológico , Regeneración Ósea/efectos de los fármacos , Fémur/efectos de los fármacos , Fémur/metabolismoRESUMEN
BACKGROUND: Thoracic aortic dissection (TAD) is one of the most fatal cardiovascular diseases. One of its important pathological characteristics is the local inflammatory response. Many studies have found that Macrophage polarization plays an extremely critical role in the inflammatory progression and tissue remodeling of TAD. Costunolide (CTD) has an improving effect on oxidative stress and inflammation in the body. However, whether it can promote the integrity of extracellular matrix in Aortic dissection and its mechanism are still unclear. METHODS: The male C57BL/6J mice were used to construct an animal model of TAD with ß-aminopropionitrile (BAPN) (100 mg/kg/day, lasting for 28 days), and then CTD (10 mg/kg or 100 mg/kg) was injected intraperitoneally for 28 days to check the survival rate, TAD incidence, aortic morphology and other indicators of the mice. Using hematoxylin-eosin (HE), Masson, Elastin van Gieson (EVG) staining, immunofluorescence (IF), and immunohistochemical staining, the study aimed to determine the therapeutic effects of CTD on an animal model with BAPN-induced TAD. To enhance the examination of the regulatory mechanism of CTD, we conducted transcriptome sequencing on arterial tissues of mice in both the BAPN group and the BAPN + CTD100 group. Next, ANG II were used to construct TAD model in vascular smooth muscle cells (VMSCs). The effects of CTD on the proliferation, migration, invasion, and apoptosis of ANG II-induced cells are to be detected. The expression of MMP2, MMP9, P65, and p-P65 in each group will be examined using Western blot. Finally, the overexpression of IκB kinaseß (IKKß) will be established in VMSCs cells to further explore the protective function of CTD. RESULTS: The result showed that CTD significantly inhibited BAPN induced mortality and TAD incidence in the animal model, improved aortic vascular morphology, promoted the integrity of extracellular matrix in TAD, reduced tissue inflammation, reduced the accumulation of M1 macrophage, promoted M2 macrophage polarization, and reduced the expression of NF-κB pathway related proteins. Mechanistically, CTD significantly weakened the proliferation, migration, invasion, and apoptosis. p-P65 protein expression of TAD cells were induced by ANG II and IKK-ß. CONCLUSION: CTD has the potential to alleviate inflammation, VSMC apoptosis, MMP2/9 levels, and enhance extracellular matrix integrity in TAD by inhibiting the NF-κB signaling pathway.
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Disección Aórtica , Disección de la Aorta Torácica , Sesquiterpenos , Masculino , Ratones , Animales , FN-kappa B/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Aminopropionitrilo/uso terapéutico , Aminopropionitrilo/farmacología , Ratones Endogámicos C57BL , Disección Aórtica/tratamiento farmacológico , Transducción de Señal , Inflamación/tratamiento farmacológico , Modelos Animales de EnfermedadRESUMEN
OBJECTIVE: Intervertebral disc degeneration (IVDD) is a major cause of morbidity and disability. Our study aimed to investigate the potential of cartilage oligomeric matrix protein (COMP) and ADAMTS7 (A disintegrin and metalloproteinases with thrombospondin motifs 7) as biomarkers for IVDD together with their functional relationship. METHODS: IVD tissues and peripheral blood samples were collected from IVDD rabbit models over 1-4 weeks. Tissues and blood samples were also collected from clinical patients those were stratified into four equal groups according to Pfirrmann IVDD grading (I-V) with baseline data collected for each participant. COMP and ADAMTS7 expression were analyzed and biomarker characteristics were assessed using linear regression and receiver operating curve (ROC) analyses. RESULTS: COMP and ADAMTS7 expression increased in tissues and serum during IVDD progression. Serum COMP (sCOMP) and serum ADAMTS7 (sADAMTS7) levels increased in a time-dependent manner following IVD damage in the rabbit model while significant positive correlations were detected between sCOMP and sADAMTS7 and Pfirrmann grade in human subjects. ROC analysis showed that combining sCOMP and sADAMTS7 assay results produced an improved diagnostic measure for IVDD compared to individual sCOMP or sADAMTS7 tests. In vitro assays conducted on human cell isolates revealed that COMP prevented extracellular matrix degradation and antagonized ADAMTS7 expression although this protective role was uncoupled under microenvironmental conditions mimicking IVDD. CONCLUSIONS: Increases in circulating COMP and ADAMTS7 correlate with IVDD progression and may play regulatory roles. Assays for sCOMP and/or sADAMTS7 levels can discriminate between healthy subjects and IVDD patients, warranting further clinical assessment.
Asunto(s)
Degeneración del Disco Intervertebral , Disco Intervertebral , Animales , Humanos , Conejos , Proteína ADAMTS7 , Biomarcadores/metabolismo , Proteína de la Matriz Oligomérica del Cartílago/metabolismo , Disco Intervertebral/patología , Degeneración del Disco Intervertebral/diagnósticoRESUMEN
ABSTRACT: A 67-year-old man underwent 18 F-FDG PET/CT for lung cancer staging. Interestingly, the PET scan revealed strip-shaped FDG uptake in the right inguinal contoured area, which was later confirmed as a right varicocele through ultrasound imaging.