ABSTRACT
Antibiotics and polycyclic aromatic hydrocarbons (PAHs) are common environmental contaminants in the aquatic region encompassing the estuary of the Yellow River and Laizhou Bay. But little information is available about the trophic transfer of antibiotics and PAHs in the marine food web of this area. This study investigated the occurrence and trophic transfer of 19 antibiotics and 16 PAHs in marine organisms from a food web of Laizhou Bay of the Yellow River estuary. Sulfonamides, fluoroquinolones, and 2 to 4-ring PAHs were the dominant contaminants in organisms. There was a significant positive correlation between the log total concentration of sulfonamides and trophic level (TL). Sulfadiazine, sulfamethazine, and erythromycin had biomagnification effects, while ciprofloxacin and ofloxacin had biological dilution effects. The log total concentration of PAHs had a significant negative correlation with TL. Naphthalene, fluorene, anthracene, pyrene, and benzo[g,h,i]perylene had biological dilution effects. The distinct correlations of trophic magnification factors Dow of antibiotics and Kow of 2 to 5-ring PAHs, indicating that the potential of these two coefficients for predicting their transfer. Risk assessment indicated that the consumption of seafood containing antibiotics and PAHs in Laizhou Bay of the Yellow River estuary posed health and carcinogenic risks to human, respectively.
Subject(s)
Anti-Bacterial Agents , Environmental Monitoring , Estuaries , Food Chain , Polycyclic Aromatic Hydrocarbons , Water Pollutants, Chemical , Polycyclic Aromatic Hydrocarbons/analysis , Water Pollutants, Chemical/analysis , Anti-Bacterial Agents/analysis , China , Risk Assessment , Humans , Rivers/chemistry , Aquatic Organisms , AnimalsABSTRACT
Cardiovascular diseases represent a global health crisis, and understanding the intricate molecular mechanisms underlying cardiac pathology is crucial for developing effective diagnostic and therapeutic strategies. Mitsugumin-53 (MG53) plays a pivotal role in cell membrane repair, has emerged as a multifaceted player in cardiovascular health. MG53, also known as TRIM72, is primarily expressed in cardiac and skeletal muscle and actively participates in membrane repair processes essential for maintaining cardiomyocyte viability. It promotes k-ion currents, ensuring action potential integrity, and actively engages in repairing myocardial and mitochondrial membranes, preserving cardiac function in the face of oxidative stress. This study discusses the dual impact of MG53 on cardiac health, highlighting its cardioprotective role during ischemia/reperfusion injury, its modulation of cardiac arrhythmias, and its influence on cardiomyopathy. MG53's regulation of metabolic pathways, such as lipid metabolism, underlines its role in diabetic cardiomyopathy, while its potential to mitigate the effects of various cardiac disorders, including those induced by antipsychotic medications and alcohol consumption, warrants further exploration. Furthermore, we examine MG53's diagnostic potential as a biomarker for cardiac injury. Research has shown that MG53 levels correlate with cardiomyocyte damage and may predict major adverse cardiovascular events, highlighting its value as a biomarker. Additionally, exogenous recombinant human MG53 (rhMG53) emerges as a promising therapeutic option, demonstrating its ability to reduce infarct size, inhibit apoptosis, and attenuate fibrotic responses. In summary, MG53's diagnostic and therapeutic potential in cardiovascular diseases presents an exciting avenue for improved patient care and outcomes.
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Blood vessels play a role in osteogenesis and osteoporosis; however, the role of vascular metabolism in these processes remains unclear. The present study finds that ovariectomized mice exhibit reduced blood vessel density in the bone and reduced expression of the endothelial glycolytic regulator pyruvate kinase M2 (PKM2). Endothelial cell (EC)-specific deletion of Pkm2 impairs osteogenesis and worsens osteoporosis in mice. This is attributed to the impaired ability of bone mesenchymal stem cells (BMSCs) to differentiate into osteoblasts. Mechanistically, EC-specific deletion of Pkm2 reduces serum lactate levels secreted by ECs, which affect histone lactylation in BMSCs. Using joint CUT&Tag and RNA sequencing analyses, collagen type I alpha 2 chain (COL1A2), cartilage oligomeric matrix protein (COMP), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and transcription factor 7 like 2 (TCF7L2) as osteogenic genes regulated by histone H3K18la lactylation are identified. PKM2 overexpression in ECs, lactate addition, and exercise restore the phenotype of endothelial PKM2-deficient mice. Furthermore, serum metabolomics indicate that patients with osteoporosis have relatively low lactate levels. Additionally, histone lactylation and related osteogenic genes of BMSCs are downregulated in patients with osteoporosis. In conclusion, glycolysis in ECs fuels BMSC differentiation into osteoblasts through histone lactylation, and exercise partially ameliorates osteoporosis by increasing serum lactate levels.
Subject(s)
Mesenchymal Stem Cells , Osteoporosis , Humans , Animals , Mice , Histones/metabolism , Lactic Acid/metabolism , Osteoporosis/metabolism , Mesenchymal Stem Cells/metabolism , Endothelial Cells/metabolismABSTRACT
Bone is a naturally mineralized tissue with a remarkable hierarchical structure, and the treatment of bone defects remains challenging. Microspheres with facile features of controllable size, diverse morphologies, and specific functions display amazing potentials for bone regeneration. Herein, inspired by natural biomineralization, a novel enzyme-catalyzed reaction is reported to prepare magnesium-based mineralized microspheres. First, silk fibroin methacryloyl (SilMA) microspheres are prepared using a combination of microfluidics and photo-crosslinking. Then, the alkaline phosphatase (ALP)-catalyzed hydrolysis of adenosine triphosphate (ATP) is successfully used to induce the formation of spherical magnesium phosphate (MgP) in the SilMA microspheres. These SilMA@MgP microspheres display uniform size, rough surface structure, good degradability, and sustained Mg2+ release properties. Moreover, the in vitro studies demonstrate the high bioactivities of SilMA@MgP microspehres in promoting the proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Transcriptomic analysis shows that the osteoinductivity of SilMA@MgP microspheres may be related to the activation of the PI3K/Akt signaling pathway. Finally, the bone regeneration enhancement units (BREUs) are designed and constructed by inoculating BMSCs onto SilMA@MgP microspheres. In summary, this study demonstrates a new biomineralization strategy for designing biomimetic bone repair materials with defined structures and combination functions.
Subject(s)
Magnesium , Osteogenesis , Microspheres , Phosphatidylinositol 3-Kinases , Bone Regeneration , Cell DifferentiationABSTRACT
Reprogramming metabolism is a hallmark of cancer cells for rapid progression. However, the detailed functional role of deubiquitinating enzymes (DUBs) in tumor glycolytic reprogramming is still unknown and requires further investigation. USP13 was found to upregulate in osteosarcoma (OS) specimens and promote OS progression through regulating aerobic glycolysis. Interestingly, the m6A writer protein, METTL3, has been identified as a novel target of USP13. USP13 interacts with, deubiquitinates, and therefore stabilizes METTL3 at K488 by removing K48-linked ubiquitin chains. Since METTL3 is a well-known m6A writer and USP13 stabilizes METTL3, we further found that USP13 increased global m6A abundance in OS cells. The results of RNA sequencing and methylated RNA immunoprecipitation sequencing indicated METTL3 could bind to m6A-modified ATG5 mRNA, which is crucial for autophagosome formation, and inhibit ATG5 mRNA decay on an IGF2BP3 dependent manner, thereby promoting autophagy and the autophagy-associated malignancy of OS. Using a small-molecule inhibitor named Spautin-1 to pharmacologically inhibit USP13 induced METTL3 degradation and exhibited significant therapeutic efficacy both in vitro and in vivo. Collectively, our study results indicate that USP13 promotes glycolysis and tumor progression in OS by stabilizing METTL3, thereby stabilizing ATG5 mRNA and facilitating autophagy in OS. Our findings demonstrate the role of the USP13-METTL3-ATG5 cascade in OS progression and show that USP13 is a crucial DUB for the stabilization of METTL3 and a promising therapeutic target for treating OS.
Subject(s)
Bone Neoplasms , Osteosarcoma , Humans , Osteosarcoma/genetics , Osteosarcoma/metabolism , Bone Neoplasms/genetics , RNA, Messenger/metabolism , Methyltransferases/genetics , Autophagy-Related Protein 5 , Ubiquitin-Specific Proteases/geneticsABSTRACT
Gut microbiota has been reported to participate in bone metabolism. However, no article has quantitatively and qualitatively analyzed this crossing field. The present study aims to analyze the current international research trends and demonstrate possible hotspots in the recent decade through bibliometrics. We screened out 938 articles meeting the standards from 2001 to 2021 in the Web of Science Core Collection database. Bibliometric analyses were performed and visualized using Excel, Citespace, and VOSviewer. Generally, the annual number of published literatures in this field shows an escalating trend. The United States has the largest number of publications, accounting for 30.4% of the total. Michigan State University and Sichuan University have the largest number of publications, while Michigan State University has the highest average number of citations at 60.00. Nutrients published 49 articles, ranking first, while the Journal of Bone and Mineral Research had the highest average number of citations at 13.36. Narayanan Parameswaran from Michigan State University, Roberto Pacifici from Emory University, and Christopher Hernandez from Cornell University were the three professors who made the largest contribution to this field. Frequency analysis showed that inflammation (148), obesity (86), and probiotics (81) are keywords with the highest focus. Moreover, keywords cluster analysis and keywords burst analysis showed that "inflammation", "obesity", and "probiotics" were the most researched topics in the field of gut microbiota and bone metabolism. Scientific publications related to gut microbiota and bone metabolism have continuously risen from 2001 to 2021. The underlying mechanism has been widely studied in the past few years, and factors affecting the alterations of the gut microbiota, as well as probiotic treatment, are emerging as new research trends.
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OBJECTIVE: Intraoperative O-arm navigation systems improve the accuracy of spinal instrumentation placement. However, deviation of the pedicle screw from the guide line might occur. The aim of the present study was to explore the causes of and countermeasures for the drift phenomenon during pedicle screw implantation with the aid of an O-arm three-dimensional navigation system in spinal deformity surgery. METHODS: This was a retrospective analysis of 341 patients with spinal deformity who underwent O-arm navigation system-assisted pedicle screw placement from July 2015 to June 2019. The patient's general condition, Cobb angle, apical vertebra position, softness index, spinal release status, fixed reference frame position, and distance between the navigation vertebral body and the reference frame were collected and compared by independent-samples t test or Pearson's chi-square analysis. The potential risk factors for the drift phenomenon were identified using binary logistic regression analysis. RESULTS: The drift phenomenon occurred in 57 patients during the first navigation-assisted pedicle screw placement, for an incidence of 16.7% (57/341). There were significant differences in factors such as the apical vertebra position, softness index, spinal release status, and distance between the vertebral body and the reference frame when the drift phenomenon occurred (P < 0.05). Binary logistic regression analysis showed that the softness index, spinal release status, and distance between the vertebral body and the reference frame when drifting occurred were independent risk factors for the drift phenomenon during O-arm navigation-assisted pedicle screw placement. CONCLUSION: During the use of an O-arm navigation system to assist with pedicle screw placement, pedicle screws should not be placed away from the reference frame, and spinal osteotomy and release should be performed after pedicle screw placement. In addition, the accuracy of O-arm navigation-assisted pedicle screw placement will be affected more in those with larger softness indices.
Subject(s)
Pedicle Screws , Spinal Fusion , Surgery, Computer-Assisted , Humans , Pedicle Screws/adverse effects , Retrospective Studies , Imaging, Three-Dimensional/methods , Tomography, X-Ray Computed/methods , Surgery, Computer-Assisted/methods , Risk Factors , Osteotomy , Spinal Fusion/methodsABSTRACT
Purpose: To provide reference data on CBT pedicle screws from CT measurements of L1 to L5 in the Chinese Han population and to assess the treatment efficacy of CBT pedicle screws in cases of lumbar degenerative disease. Methods: In total, 100 patients were identified from the CT database for CBT morphometric measurement of the lumbar spine. According to sex and age, patients were divided into four groups. The diameter, length, and angle of the vertebral pedicle and trajectory were measured. Then, a total of 36 patients with lumbar degenerative disease were included in this study for clinical and radiographic evaluation. Demographic characteristics, health-related quality of life (HRQOL), and extent of intervertebral disc herniation and spondylolisthesis were evaluated. Results: The mean diameter and the mean length varied from L1 to L5 in Groups I to IV. The lateral angles ranging from L1 to L5 were 8.9 to 9.2°, 8.7 to 12.2°, 8.7 to 11.2°, and 9.2 to 10.1° in Groups I to IV, respectively. The cephalad angles from L1 to L5 were 23.5 to 28.6°, 24.7 to 26.6°, 25.0 to 28.2°, and 24.7 to 27.9° in Groups I to IV, respectively. In the case series, all patients' neurological function and HRQOL were significantly improved at the final follow-up (p < 0.0001), and 75% of patients achieved satisfaction. Conclusions: The morphology of the lumbar vertebral pedicle varied from L1 to L5, and the trajectory was feasible and safe. CBT pedicle screws were effective in treating lumbar degenerative diseases and benefited the patients.
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STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the cross-cultural adaptability and internal consistency of the Chinese version of the Quality-of-Life Profile for Spine Deformities (QLPSD) questionnaire in mainland China. METHODS: The original QLPSD was translated from Spanish into Chinese with proper cross-cultural adaptation based on the American Academy of Orthopaedic Surgeons guidelines. A total of 129 AIS patients referring to our institution from February 2021 to January 2022 were enrolled in this study. The effects of ceiling and floor were evaluated and the reliability was verified by examining the internal consistency (the Cronbach's α coefficient). Interclass Correlation Coefficient (ICC) was used to test and retest reliability. The C-QLPSD dimensions were compared with the domains in Chinese version of 36-Item Short Form Health Survey (SF-36) and Scoliosis Research Society-22 (SRS-22) questionnaires using Pearson correlation coefficient to assess the concurrent validity. RESULTS: No significant floor and ceiling effects in C-QLPSD was observed. The total Cronbach's α was estimated at .914, ranging from .768 in back pain dimensions to .862 in psychosocial function dimensions. The C-QLPSD dimensions indicated satisfactory test-retest reliability with ICC range of .784-.870. Construct validity analysis revealed that C-QLPSD was well correlated with SRS-22 and SF-36. The values of total correlation coefficient were calculated at -.924 and -.871, respectively, which were both statistically significant (P < .05). CONCLUSION: The adapted Chinese version of QLPSD had good internal consistency and excellent test-retest reliability, which can be used to assess the outcome among Chinese-speaking patients with adolescent idiopathic scoliosis.
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Background: Patients with severe posttuberculous (TB) kyphosis might suffer from late-onset neurological deficits, and surgical correction may improve neurological function. However, there is a lack of predictive factors for neurological function in these patients. Objective: This study was aimed at identifying the risk factors for late-onset neurological deficits in spinal TB patients at initial and final assessments. Methods: Seventy-eight patients with severe kyphosis caused by old thoracic tuberculosis were retrospectively analyzed. Patients with active spinal TB and other spinal diseases were excluded from the analysis. The kyphosis Cobb angle, sagittal deformity angular ratio (S-DAR), and level of apex were measured and calculated on X-ray. The spinal cord cross-sectional area ratio (CSAR), spinal cord sagittal diameter ratio (SDR), and spinal cord angle (SCA) were measured on preoperative T2-weighted magnetic resonance imaging (MRI). According to the American Spinal Injury Association (ASIA) Impairment Scale (AIS) at the time of admission, the patients were divided into the symptomatic group (N = 60 patients, AIS grades A to D) and the asymptomatic group (N = 18 patients, AIS grade E). All of the symptomatic patients underwent surgery, and the patients from both groups had at least 2 years of follow-up. Relationships among the radiological parameters and initial and final AIS grades were evaluated via univariate and multivariate analyses. Results: The mean duration of kyphotic deformity was 37.4 years in the symptomatic group. There were no significant differences between the two groups in terms of CSAR, kyphosis Cobb angle, S-DAR, level of apex, or the segments that were involved. Patients from the symptomatic group exhibited significantly greater SDR and smaller SCA than those from the asymptomatic group (p < 0.01 and p < 0.01, respectively). The multivariate logistic regression identified SDR and SCA as independent factors influencing the likelihood of spinal cord injury at the initial and final assessments. Conclusions: Severe posttuberculous kyphosis may lead to significant neurological symptoms many years following the initial treatment. The predictive factors for late-onset neurological deficits include larger SDR and smaller SCA.
Subject(s)
Kyphosis , Spinal Cord Injuries , Humans , Kyphosis/diagnostic imaging , Kyphosis/surgery , Radiography , Retrospective Studies , Spinal Cord Injuries/complications , SpineABSTRACT
OBJECTIVE: The purpose of this study was to compare the traditional 2-rod correction technique with the sectional correction technique in terms of radiographic results and clinical outcomes for patients with dystrophic scoliosis caused by neurofibromatosis type 1 (NF1). METHODS: From May 2015 to April 2018, 53 patients with dystrophic scoliosis caused by NF1 underwent 1-stage posterior corrective surgery. Patients were separated into 2 groups based on technique: the sectional correction technique (SC group) and the traditional 2-rod technique (TT group). Before surgery and at the final follow-up, the demographic information, radiographic parameters, and clinical outcomes were compared between the groups using independent-sample t tests. RESULTS: The SC group consisted of 24 patients, while the TT group consisted of 29 patients. Patients in the SC group showed a higher coronal balance distance after the operation (8.3 ± 8.2 mm vs. 16.2 ± 8.8 mm, P = 0.002) and at the final follow-up (9.5 ± 9.3 mm vs. 19.3 ± 10.1 mm, P < 0.0001). At the last follow-up, the loss of correction in the SC group was 2.2 ± 0.9 and 2.1 ± 0.7 in the coronal and sagittal planes, respectively, and these values were significantly lower than those in the TT group (5.3 ± 1.6 in the coronal plane and 4.5 ± 1.9 in the sagittal plane, both P < 0.05). The SC group had better improvement based on appearance and satisfaction score at the final follow-up. CONCLUSIONS: The sectional correction technique using a concave domino connector can restore coronal imbalance and reduce the risk of implant failure.
Subject(s)
Neurofibromatosis 1 , Pedicle Screws , Scoliosis , Spinal Fusion , Humans , Scoliosis/diagnostic imaging , Scoliosis/etiology , Scoliosis/surgery , Neurofibromatosis 1/complications , Neurofibromatosis 1/diagnostic imaging , Neurofibromatosis 1/surgery , Spinal Fusion/methods , Pedicle Screws/adverse effects , Personal Satisfaction , Retrospective Studies , Treatment Outcome , Thoracic Vertebrae/surgeryABSTRACT
BACKGROUND: The position of the aorta relative to the spine in kyphosis secondary to Pott's deformity is little understood. The purpose of this study was to investigate the anatomic relationship between the aorta and the spine in patients with Pott's deformity and to compare it with the normal people. METHODS: Seventy-six patients with Pott's deformity (Group TB) and seventy-two age- and sex-matched patients with a normal spine (group NC) were enrolled in this study. The relative position of aorta to the spine was evaluated from T4 to L4 on the computed tomographic angiography scans for controls and at the apex level for TB patient, and was classified into 4 kinds of degrees. RESULTS: The left pedicle-aorta angle in group TB was significantly larger than that in group NC at the T6-L3 levels. Group TB exhibited significantly smaller left pedicle-aorta distance, pedicular line-aorta distance and vertebra/rib-aorta distance than those in group NC at the T5-T10 levels, but bigger at the L1-3 levels. Patients with grade 3 and 4 aorta had more segments involved compared with those with grade 1 aorta. Patients with grade 2, 3, and 4 aorta showed larger kyphotic angles than those with grade 1. CONCLUSIONS: Patients whose morbid segments involved only thoracic vertebrae presented with an "Ω" shaped aorta in sagittal plane, and 4 different kinds of degrees of aorta relative to the vertebra/rib in axial plane. Patients whose morbid segments covered lumbar vertebrae presented with an "M" shaped aorta in sagittal plane, and the aorta shifted further from apex vertebra but was located in close proximity to the vertebral body at levels above and below the osteotomy levels in axial plane.
Subject(s)
Kyphosis , Musculoskeletal Abnormalities , Spinal Fusion , Aorta/diagnostic imaging , Humans , Kyphosis/diagnostic imaging , Kyphosis/etiology , Kyphosis/surgery , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Osteotomy/methods , Spinal Fusion/methods , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgeryABSTRACT
OBJECTIVE: Subarachnoid hemorrhage (SAH) is a rare complication secondary to cerebrospinal fluid (CSF) leakage during spinal surgery, but the specific cause of bleeding is still unclear. In this retrospective single-center study, we studied cases of acute SAH after spinal surgery to identify the related risk factors for bleeding. METHODS: A total of 441 patients with CSF leakage who underwent spinal surgery from 2011 to 2020 were retrospectively analyzed. According to whether postoperative SAH occurred, the patients were divided into the SAH group and the control group. By comparing the demographic data, past history, imaging data, intraoperative findings, perioperative complications, and treatment conditions in the 2 groups to identify the risk factors for SAH, we aimed to provide guidance for the prevention of SAH after spinal surgery. RESULTS: In our study, the incidence of CSF during spinal surgery is 3.04%, and the rate for SAH associated with spine operation is 0.16%. In the SAH group, 17 patients (73.9%) had preoperative hypertension, and 3 patients (13.0%) had diabetes. The intraoperative CSF leakage was approximately 118.4 ± 56.9 mL. The mean postoperative drainage was 15.4 ± 5.8 mL/hour. Compared with the SAH group, the control group had 123 patients (29.4%) with hypertension before the operation and 40 patients (9.6%) with diabetes. The intraoperative CSF leakage was approximately 76.3 ± 23.0 mL, and the mean postoperative continuous drainage was 9.7 ± 2.1 mL/hour. Binary logistic regression analysis showed that hypertension, intraoperative CSF leakage, and postoperative CSF continuous drainage speed were related to SAH. CONCLUSIONS: The rapid leakage of CSF caused by rupture of the dural sac during surgery and the rapid drainage of CSF after surgery were closely related to the occurrence of SAH. In addition, hypertension was a factor related to SAH during spinal surgery.
Subject(s)
Subarachnoid Hemorrhage , Humans , Neurosurgical Procedures/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Retrospective Studies , Risk Factors , Subarachnoid Hemorrhage/diagnostic imaging , Subarachnoid Hemorrhage/epidemiology , Subarachnoid Hemorrhage/etiologyABSTRACT
BACKGROUND: The association of myocardial bridge (MB) with cardiovascular risk and the possible cardiovascular risk factors remain unclear. This study aimed to explore the clinical characteristics and related factors of coronary stenosis proximal to an MB. METHODS: This was a retrospective study of patients with symptoms of coronary atherosclerotic heart disease admitted between 10/2011 and 12/2014 to the Emergency and Cardiology Department of Bayannur Hospital, who underwent selective coronary angiography (SCAG). The patients were assigned to the non-stenosis and stenosis groups according to whether coronary stenosis was proximal to the MB. RESULTS: Among 244 patients with MB and cardiovascular symptoms, 91 (37.3%) had stenosis proximal to the MB. Compared with the non-stenosis group, there were more males (80.2% vs. 55.6%, P < 0.001) and smokers (including those who had quit smoking) (P < 0.001) in the stenosis group. There were no significant differences in blood lipid-related indexes (TG, TC, HDL-C, LDL-C, and VLDL-C) between the two groups. Multivariable analysis suggested that MB location in the middle distal or distal segment of the left anterior descending artery (LAD) increased the odds of coronary stenosis proximal to the MB (OR = 0.439, 95% CI: 1.57-7.532, P = 0.002), which was then considered an independent factor associated with coronary stenosis proximal to the MB. CONCLUSIONS: In patients diagnosed with an MB by SCAG, only MB located in the middle distal or distal segment of the LAD is independently associated with coronary stenosis proximal to the MB.
Subject(s)
Coronary Stenosis/etiology , Myocardial Bridging/complications , Aged , Coronary Angiography , Coronary Stenosis/diagnostic imaging , Female , Humans , Male , Middle Aged , Myocardial Bridging/diagnosis , Retrospective Studies , Risk Assessment , Risk FactorsABSTRACT
BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a genetically heterogeneous disease characterised by three-dimensional deformity of the spine in the absence of a congenital spinal anomaly or neurological musculoskeletal disorder. The clinical variability and incomplete penetrance of some genes linked with AIS indicate that this disease constitutes an oligogenic trait. OBJECTIVE: We aimed to explore the oligogenic nature of this disease and identify novel AIS genes. METHODS: We analysed rare damaging variants within AIS-associated genes by using exome sequencing in 40 AIS trios and 183 sporadic patients. RESULTS: Multiple variants within AIS-associated genes were identified in eight AIS trios, and five individuals harboured rare damaging variants in the FLNB gene. The patients showed more frequent oligogenicity than the controls. In the gene-based burden test, the top signal resided in FLNB. In functional studies, we found that the AIS-associated FLNB variants altered the protein's conformation and subcellular localisation and its interaction with other proteins (TTC26 and OFD1) involved in AIS. The most compelling evidence of an oligogenic basis was that the number of rare damaging variants was recognised as an independent prognostic factor for curve progression in Cox regression analysis. CONCLUSION: Our data indicate that AIS is an oligogenic disease and identify FLNB as a susceptibility gene for AIS.
Subject(s)
Filamins/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Scoliosis/genetics , Adolescent , Child , Exome/genetics , Female , Filamins/ultrastructure , Genetic Testing , Genetic Variation/genetics , Humans , Male , Polymorphism, Single Nucleotide/genetics , Protein Conformation , Proteins/genetics , Scoliosis/pathology , Exome SequencingABSTRACT
The development of two-dimensional (2D) nanohybrid materials with heterogeneous components in nanoscale and three-dimensional (3D) well-ordered assembly in microscale has been regarded as an effective way to improve their overall performances by the synergistic coupling of the optimized structure and composition. In this work, we reported the design and synthesis of a new type of hierarchically core-shell structure of 2D VS2@VC@N-doped carbon (NC) sheets decorated by ultrafine Pd nanoparticles (PdNPs), which were vertically grown on carbon fiber (CF) and assembled into a unique 3D rosette-like array. The resultant VS2@VC@NC-PdNPs modified CF microelectrode integrated the structural and electrochemical properties of the heterogeneous hybridization of core-shell VS2@VC@NC-PdNPs sheets with a unique rosette-like array structure, and gave rise to a significant improvement in terms of electron transfer ability, electrocatalytic activity, stability, and biocompatibility. Under the optimized conditions, the VS2@VC@NC-PdNPs modified CF microelectrode demonstrated excellent electrochemical sensing performance towards biomarker hydrogen peroxide (H2O2) including a high sensitivity of 152.7 µA cm-2 mM-1, a low detection limit of 50 nM (a signal-to-noise ratio of 3:1), as well as good reproducibility and anti-interference ability, which could be used for the real-time in situ electrochemical detection of H2O2 in live cancer cells and cancer tissue. The remarkable performances of the proposed nanohybrid microelectrode will have a profound impact on the design of diverse 2D layered materials as a promising candidate for electrochemical biosensing applications.
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BACKGROUND: Identify genes probably associated with chronic heart failure and predict potential target genes for dilated cardiomyopathy using bioinformatics analyses. METHODS: Gene expression profiles (series number GSE3585 and GSE42955) of cardiomyopathy patients and healthy controls were downloaded from the Expression Omnibus Gene (GEO) database. Differential expression of genes (DEGS) between the two groups of total 14 cardiomyopathy patients and 10 healthy controls were subsequently identified by limma package of R. Database for Annotation, Visualization, and Integrated Discovery (DAVID Tool), which is an analysis of enriched biological processes. Search Tool for the Retrieval Interacting Genes (STRING) was used as well for the analysis of protein-protein interaction network (PPI). Prediction of the potential drugs was suggested based on the preliminarily identified genes using Connectivity Map (CMap). RESULTS: Eighty-nine DEGs were identified (57 up-regulated and 32 down-regulated). The most enrichment Gene Ontology (GO) terms (P < 0.05) contain genes involved in extracellular matrix (ECM) and biological adhesion signal pathways (P < 0.05, ES > 1.5) such as ECM-receptors, focal adhesion and transforming growth factor beta (TGF-ß), etc. Fifty-one differentially expressed genes were found to encode interacting proteins. Eleven key genes along with related transcription factors were identified including CTGF, POSTN, CORIN, FIGF, etc. CONCLUSION: Bioinformatics-based analyses reveal the targeted genes probably associated with cardiomyopathy, which provide clues for pharmacological therapies aiming at the targets.
Subject(s)
Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Dilated/physiopathology , Transcriptome , Computational Biology , Gene Expression Profiling , HumansABSTRACT
BACKGROUND LPS-inhibited osteoblastic differentiation plays an important role in the pathogenesis of osteomyelitis. Thus, searching for drugs that affect LPS-mediated osteoblastic differentiation may be crucial in developing therapies for osteomyelitis. The purpose of this study was to investigate the role and mechanisms of resveratrol, a natural polyphenol present in red wine, on LPS-inhibited osteoblastic differentiation. MATERIAL AND METHODS Cell viability was measured by MMT assay. Mitochondrial ATP levels, membrane potential, and superoxide production were measured to evaluate the effects of LPS and resveratrol on mitochondrial functions in osteoblast-like MC3T3-E1 cells. Osteoblast-related genes, including ALP, OCN, OPN, and RUNX2, were measured by ELISA analysis and RT-PCR in differentiated osteoblast cells treated with LPS and resveratrol. Cellular Sirt1 and PCG-1α levels were measured by Western blot to probe the impact of resveratrol treatment in LPS-stimulated MC3T3-E1 osteoblasts. RESULTS The results showed that LPS caused significant mitochondrial dysfunctions of MC3T3-E1 cells in a dose-dependent manner, which were attenuated by resveratrol. Furthermore, LPS markedly decreased the expression of ALP, OCN, OPN, and RUNX2 in MC3T3-E1 cells cultivated in osteoblast differentiation medium, suggesting that LPS inhibited the osteoblastic differentiation of MC3T3-E1 cells. However, resveratrol obviously alleviated the suppressive impact of LPS on osteoblast differentiation. In addition, resveratrol increased expression of Sirt1 and PGC-1α in MC3T3-E1 cells treated with LPS. CONCLUSIONS Taken together, these results show that resveratrol alleviated the suppression of LPS on osteoblast differentiation by improving, at least in part, mitochondrial function.
Subject(s)
Osteoblasts/drug effects , Stilbenes/pharmacology , 3T3 Cells/drug effects , Animals , Apoptosis/drug effects , Cell Differentiation/drug effects , Cell Line , Cell Survival/drug effects , Lipopolysaccharides/metabolism , Mice , Mitochondria/drug effects , Osteoblasts/metabolism , Osteogenesis/drug effects , Resveratrol , Stilbenes/metabolismABSTRACT
Hierarchically ordered macro-mesoporous anatase TiO2 is prepared by combining the supramolecular-templating self-assembly of amphiphilic triblock copolymer P123 with a natural pearl oyster shell in a hard-templating process by a facile sol-gel reaction. The obtained materials are characterized by Raman spectroscopy, X-ray diffraction, N2 adsorption-desorption analysis, scanning electron microscopy, and transmission electron microscopy. The results demonstrate that all TiO2 materials obtained after calcination at various temperatures are in the anatase phase, and interestingly the resultant ordered structure of both macropores and mesopores are well-preserved after calcination at 350 °C or 450 °C, with the walls of macropores composed of ordered mesopores. However, upon calcination at 550 °C or 650 °C, while the ordered macroporous structures remain well-preserved, the mesoporous structures collapse. The photocatalytic activities of the resulting TiO2 materials are also evaluated by photodegradation of rhodamine B under UV light irradiation. The prepared TiO2 calcined at 450 °C shows the highest photocatalytic activity.
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BACKGROUND Several studies have described the differences in electromyographic activity and histological changes of paravertebral muscles in patients with adolescent idiopathic scoliosis (AIS). However, there is little knowledge about the muscle volumetric and fatty infiltration imbalance of patients with AIS. MATERIAL AND METHODS Thirty-four patients with AIS were evaluated with standardized anteroposterior (AP) and lateral standing films for the location and direction of the apex of scoliosis, coronal Cobb angle, apex vertebra translation, and thoracic kyphosis; and with magnetic resonance imaging (MRI) scan of the spine at the level of T4-L1. The muscle volume and fatty infiltration rate of bilateral deep paravertebral muscles at the level of upper end, apex, and lower end vertebra were measured. RESULTS All patients had major thoracic curve with apex of curves on the right side. The muscle volume on the convex side was larger relative to the concave side at the three levels, while the fatty infiltration rate was significantly higher on the concave side. The difference index of the muscle volume was significantly larger at the apex vertebra level than at the upper end vertebra level (p=0.002) or lower end vertebra level (p<0.001). The difference index of muscle volume correlated with apex vertebra translation (r=-0.749, p=0.032), and the difference index of fatty involution correlated with apex vertebra translation (r=0.727, p=0.041) and Cobb angle (r=0.866, p=0.005). CONCLUSIONS Our findings demonstrated significant imbalance of muscle volume and fatty infiltration in deep paravertebral muscles of AIS patients. Moreover, these changes affected different vertebra levels, with the most imbalance of muscle volume at the apex vertebra. We interpreted this as morphological changes corresponding with known altered muscle function of AIS.