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1.
J Neurosurg Spine ; : 1-11, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39241259

ABSTRACT

OBJECTIVE: Robot guidance (RG) and computer-assisted navigation (CAN) have been increasingly utilized for posterior cervical screw placement in cervical spine surgery, and cervical screw malposition may contribute to catastrophic complications. However, the superiority of the navigation using RG or CAN compared with conventional freehand (FH) techniques remains controversial, and no meta-analysis comparing the two methods in cervical spine surgery has been performed. METHODS: The PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure, and Wanfang databases were searched for eligible literature. Studies reporting the primary outcomes of the accuracy of cervical screw placement using RG or CAN compared with FH techniques were included. Bias was evaluated using the Cochrane risk of bias criteria and the Newcastle-Ottawa Scale. The outcomes were evaluated in terms of odds ratio or standardized mean difference and corresponding 95% confidence interval. RESULTS: One randomized controlled trial and 18 comparative cohort studies published between 2012 and 2023 consisting of 946 patients and 4163 cervical screws were included in this meta-analysis. The RG and CAN techniques were associated with a substantially higher rate of optimal and clinically acceptable cervical screw accuracy than FH techniques. Furthermore, compared with the FH group, the navigation group showed fewer postoperative adverse events, less blood loss, shorter hospital lengths of stay, and lower postoperative Neck Disability Index scores. However, the navigation and FH groups had equivalent intraoperative times and postoperative visual analog scale and Japanese Orthopaedic Association scores at the final follow-up. CONCLUSIONS: Both RG and CAN are superior to FH techniques in terms of the accuracy of cervical screw placement. Navigation techniques, including RG and CAN methods, are accurate, safe, and feasible in cervical spine surgery.

2.
J Hepatocell Carcinoma ; 11: 1713-1725, 2024.
Article in English | MEDLINE | ID: mdl-39268150

ABSTRACT

Purpose: To determine the effect of aspirin on hepatocellular carcinoma (HCC) recurrence and survival after thermal ablation. Methods: A retrospective analysis was performed to evaluate the efficacy and safety of aspirin in combination with thermal ablation. The clinical data were collected for the enrolled patients. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed. Results: A total of 174 patients with HCC were enrolled. The median PFS was 11.1 (95% confidence interval [CI]: 8.1-14.0) months for patients who took aspirin and 8.6 (95% CI: 5.5-11.8) months for patients who did not take aspirin. The median OS of patients in the aspirin group was 76.7 (95% CI: 58.1-95.3) months and that in the non-aspirin group was 53.5 (95% CI: 42.7-64.3) months. In patients with non-viral HCC, OS was significantly better for the aspirin group (P = 0.03) after ablation. The PFS of patients who underwent ablation alone in the aspirin group was obviously superior to that of patients in the non-aspirin group (P = 0.002). Stratified Cox regression analysis demonstrated that aspirin use after ablation might be a protective factor in specific HCC patient subgroups. The incidence of major adverse events did not significantly differ between the two groups. Conclusion: Low-dose aspirin use was associated with better OS in patients with non-viral HCC after thermal ablation. In patients who received thermal ablation alone, the administration of low-dose aspirin could improve PFS. Aspirin use might be a protective factor in some patients after ablation.

3.
Clin Nucl Med ; 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39325544

ABSTRACT

ABSTRACT: A 2-and-a-half-year-old boy with a previous history of Langerhans cell histiocytosis reached remission as assessed by 18F-FDG PET/CT. Routine follow-up 18F-FDG PET/CT revealed the appearance of new bone lesions in the right scapula and right ischium with abnormal FDG activity 3 months after the end of treatment, and Langerhans cell histiocytosis recurrence was considered. Meanwhile, these lesions also showed increased FAPI uptake. After adjusting the chemotherapy regimen, both FDG and FAPI uptake almost disappeared in these lesions.

4.
Front Oncol ; 14: 1419020, 2024.
Article in English | MEDLINE | ID: mdl-39319057

ABSTRACT

Since the onset of the COVID-19 pandemic, the SARS-CoV-2 virus has caused over 600 million confirmed infections and more than 6.8 million deaths worldwide, with ongoing implications for human health. COVID-19 has been extensively documented to have extrapulmonary manifestations due to the widespread expression of necessary ACE2 receptors in the human body. Nevertheless, the association between COVID-19 and cancer risk remains inadequately explored. This study employs Mendelian randomization (MR) methods to examine the causal relationship between genetic variations associated with COVID-19 and the risk of developing cancer. The findings indicate that COVID-19 has negligible impact on most cancer risks. Interestingly, a higher COVID-19 impact is associated with a decreased risk of thyroid cancer. In summary, our findings demonstrate a genetic correlation between COVID-19 and thyroid cancer, contributing to our understanding of the interplay between COVID-19 and cancer risk.

5.
Mol Metab ; 89: 102026, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39299533

ABSTRACT

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is deemed as an emerging global epidemic, whereas the underlying pathogenic mechanism remains to be clarified. We aimed to systemically analyze all the NAFLD-related gene expression datasets from published human-based studies, by which exploring potential key factors and mechanisms accounting for the pathogenesis of NAFLD. METHODS: Robust rank aggregation (RRA) method was used to integrate NAFLD-related gene expression datasets. For fatty liver study, adeno-associated virus (AAV) delivery and genetic knockout mice were used to create IGFBP2 (Insulin-like growth factor binding protein 2) gain- or loss-of function models. Western blot, Co-immunoprecipitation (Co-IP), immunofluorescent (IF) staining, luciferase assay, molecular docking simulation were performed to reveal the IGFBP2-EGFR-STAT3 axis involved. Key axis protein levels in livers from healthy donors and patients with NAFLD were assessed via immunohistochemical staining. RESULTS: By using RRA method, the present study identified IGFBP2 being the most significantly down-regulated gene in all NAFLD subjects. The decreased IGFBP2 expression was further confirmed in the liver tissues from patients and animal models of NAFLD. IGFBP2 deficiency aggravated hepatic steatosis and NASH phenotypes and promoted lipogenic gene expression both in vivo and in vitro. Mechanistically, IGFBP2 directly binds to and regulates EGFR, whereas blockage of the IGFBP2-EGFR complex by knockdown of IGFBP2 resulted in the EGFR-STAT3 pathway activation, which in turn promoted the promoter activity of Srebf1. By using molecular docking simulation and protein-protein interaction analysis, the sequence of 233-257 amino acids in IGFBP2 was characterized as a key motif responding for its specific binding to EGFR and the protective effect against hepatic steatosis. CONCLUSIONS: The current study has, for the first time, identified IGFBP2 as a novel protector against hepatosteatosis. The protective effect is mediated by its specific interaction with EGFR and thereby suppressing the EGFR-STAT3 pathway. Therefore, pharmaceutically targeting the IGFBP2-EGFR-STAT3 axis may provide a theoretical basis for for the treatment of NAFLD/NASH and the associated diseases.

6.
BMC Musculoskelet Disord ; 25(1): 664, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39182026

ABSTRACT

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.


Subject(s)
Finite Element Analysis , Lumbar Vertebrae , Range of Motion, Articular , Spinal Fusion , Spondylolisthesis , Humans , Spinal Fusion/methods , Spinal Fusion/instrumentation , Spondylolisthesis/surgery , Spondylolisthesis/diagnostic imaging , Spondylolisthesis/physiopathology , Lumbar Vertebrae/surgery , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/physiopathology , Biomechanical Phenomena/physiology , Pedicle Screws , Male , Tomography, X-Ray Computed , Middle Aged
7.
Int Immunopharmacol ; 141: 113016, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39182269

ABSTRACT

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 SIRT3,BMP2,SOD2 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.


Subject(s)
Iron Overload , Oxidative Stress , Animals , Oxidative Stress/drug effects , Iron Overload/metabolism , Mice , Rats , Male , RAW 264.7 Cells , Rats, Sprague-Dawley , Osteoclasts/drug effects , Osteoclasts/metabolism , Sirtuin 3/metabolism , Sirtuin 3/genetics , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteoporosis/metabolism , Osteoporosis/etiology , Osteoporosis/drug therapy , Benzaldehydes/pharmacology , Benzaldehydes/therapeutic use , Inflammation , Osteogenesis/drug effects , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Bone Density/drug effects , Cell Differentiation/drug effects , Aging , Disease Models, Animal , Superoxide Dismutase/metabolism , Sirtuins
8.
Bone Joint Res ; 13(9): 427-440, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39216851

ABSTRACT

Aims: This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. Methods: In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload. Results: Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with reductions in bone metabolism, oxidative stress, and inflammation. To elucidate whether these effects are associated with osteoclast and osteoblast activity, we conducted in vitro experiments using MC3T3-E1 cells and RAW264.7 cells. Our findings indicate that iron accumulation suppressed the activity of MC3T3-E1 while enhancing RAW264.7 function. Furthermore, iron overload significantly decreased oxidative stress levels; however, these detrimental effects can be mitigated by VIT treatment. Conclusion: Collectively, our data provide compelling evidence that VIT has the potential to reverse the deleterious consequences of iron overload on osseointegration and bone mass during ageing.

9.
Clin Nucl Med ; 49(10): 993-994, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39150363

ABSTRACT

ABSTRACT: A 49-year-old woman patient with thyroid cancer accepted thyroidectomy and parathyroid transplantation. One month later, localized 131 I uptake in the deltoid muscle bilaterally was detected by 131 I whole-body imaging performed in 2 days after 131 I administration.


Subject(s)
Deltoid Muscle , Iodine Radioisotopes , Parathyroid Glands , Female , Humans , Middle Aged , Deltoid Muscle/diagnostic imaging , Deltoid Muscle/metabolism , Iodine Radioisotopes/administration & dosage , Iodine Radioisotopes/pharmacokinetics , Parathyroid Glands/diagnostic imaging , Parathyroid Glands/metabolism , Parathyroid Glands/transplantation , Whole Body Imaging
10.
Chem Biol Interact ; 401: 111164, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39111524

ABSTRACT

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.


Subject(s)
Cell Differentiation , Heptanoic Acids , Inflammation , Lanosterol , Lipopolysaccharides , Osteoclasts , Osteogenesis , Oxidative Stress , Rats, Sprague-Dawley , Superoxide Dismutase , Animals , Lipopolysaccharides/pharmacology , Oxidative Stress/drug effects , Male , Mice , Rats , RAW 264.7 Cells , Superoxide Dismutase/metabolism , Inflammation/metabolism , Inflammation/drug therapy , Osteoclasts/drug effects , Osteoclasts/metabolism , Cell Differentiation/drug effects , Osteogenesis/drug effects , Lanosterol/analogs & derivatives , Lanosterol/pharmacology , Lanosterol/therapeutic use , Heptanoic Acids/pharmacology , Heptanoic Acids/therapeutic use , Bone Density/drug effects , Tumor Necrosis Factor-alpha/metabolism , Bone Resorption/prevention & control , Bone Resorption/drug therapy , Bone Resorption/metabolism
11.
Soc Forces ; 103(1): 350-373, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39015248

ABSTRACT

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.

12.
Angew Chem Int Ed Engl ; : e202411722, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39081066

ABSTRACT

Thermally-induced dehydrogenative coupling of polyphenylenes on metal surfaces is an important technique to synthesize 𝜋-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.

13.
Eur Radiol ; 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38907099

ABSTRACT

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.

14.
J Neurosurg Spine ; 41(2): 199-208, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38788239

ABSTRACT

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.


Subject(s)
Cortical Bone , Lumbar Vertebrae , Humans , Lumbar Vertebrae/surgery , Lumbar Vertebrae/diagnostic imaging , Cortical Bone/surgery , Cortical Bone/diagnostic imaging , Aged , Female , Male , Middle Aged , Osteoporosis/surgery , Osteoporosis/diagnostic imaging , Bone Density/physiology , Bone Screws , Tomography, X-Ray Computed , Spinal Fusion/methods , Spinal Fusion/instrumentation
15.
Mol Plant ; 17(6): 935-954, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38720462

ABSTRACT

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.


Subject(s)
Flowers , Gene Expression Regulation, Plant , Oryza , Plant Proteins , RNA, Messenger , RNA-Binding Proteins , Ribonucleoproteins , Oryza/metabolism , Oryza/genetics , Oryza/growth & development , Plant Proteins/metabolism , Plant Proteins/genetics , Flowers/metabolism , Flowers/growth & development , Flowers/genetics , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , RNA, Messenger/metabolism , RNA, Messenger/genetics , Ribonucleoproteins/metabolism , Adenosine/analogs & derivatives , Adenosine/metabolism
16.
Ann Nucl Med ; 38(7): 483-492, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38573411

ABSTRACT

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.


Subject(s)
Neuroendocrine Tumors , Organometallic Compounds , Positron Emission Tomography Computed Tomography , Humans , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/metabolism , Male , Female , Middle Aged , Retrospective Studies , Aged , Adult , Biological Transport , Aged, 80 and over , Image Processing, Computer-Assisted/methods
18.
Mol Imaging Biol ; 26(4): 658-667, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38627276

ABSTRACT

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.


Subject(s)
Fluorodeoxyglucose F18 , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Peptides, Cyclic , Positron Emission Tomography Computed Tomography , Humans , Positron Emission Tomography Computed Tomography/methods , Fluorodeoxyglucose F18/chemistry , Nasopharyngeal Carcinoma/diagnostic imaging , Nasopharyngeal Carcinoma/pathology , Male , Female , Middle Aged , Adult , Peptides, Cyclic/chemistry , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharyngeal Neoplasms/pathology , Aged , Coordination Complexes/chemistry , Prospective Studies
19.
J Biomater Appl ; 38(10): 1073-1086, 2024 05.
Article in English | MEDLINE | ID: mdl-38569649

ABSTRACT

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.


Subject(s)
Calcium Phosphates , Osteogenesis , Rats, Sprague-Dawley , Animals , Osteogenesis/drug effects , Female , Mice , Calcium Phosphates/chemistry , Rats , Ovariectomy , Cell Line , Osteoporosis/drug therapy , Bone Regeneration/drug effects , Femur/drug effects , Femur/metabolism
20.
Clin Nucl Med ; 49(9): e480-e481, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38598743

ABSTRACT

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.


Subject(s)
Fluorodeoxyglucose F18 , Neoplasm Metastasis , Neuroblastoma , Positron Emission Tomography Computed Tomography , Humans , Neuroblastoma/diagnostic imaging , Neuroblastoma/pathology , Male , Female , Tomography, X-Ray Computed , Child, Preschool , Child
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