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BACKGROUND AND OBJECTIVE: The objective of this study was to investigate the potential of salidroside (SAL) (a major active compound in Rhodiola rosea L.) in regulating osteoclast differentiation and function by modulating the HIF-1α pathway and its downstream target genes. METHODS: The expression of HIF-1α and its downstream target genes was examined at both mRNA and protein levels in osteoclasts treated with SAL. Immunofluorescence analysis was performed to assess the nuclear translocation and transcriptional activity of HIF-1α in response to SAL. MTT, flow cytometry, qPCR, TRAP staining and bone resorption assays were used to evaluate the potential effect of salidroside on osteoclasts. RESULTS: SAL enhanced the expression of HIF-1α and its downstream target genes in osteoclasts. Immunofluorescence analysis confirmed the facilitation of HIF-1α nuclear translocation and transcriptional activity by SAL. In addition, SAL enhanced osteoclast viability, differentiation and bone resorption activity in an autocrine manner through HIF-1α/VEGF, IL-6 and ANGPTL4 pathways. CONCLUSION: SAL promotes osteoclast proliferation, differentiation and bone resorption through HIF-1α/VEGF, IL-6 and ANGPTL4 pathways.
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Glucósidos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Osteoclastos , Osteogénesis , Fenoles , Glucósidos/farmacología , Fenoles/farmacología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Osteoclastos/efectos de los fármacos , Animales , Ratones , Osteogénesis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Células RAW 264.7 , Interleucina-6/metabolismo , Interleucina-6/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Resorción Ósea , Transducción de Señal/efectos de los fármacos , Proteína 4 Similar a la Angiopoyetina/metabolismo , Proteína 4 Similar a la Angiopoyetina/genética , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacosRESUMEN
BACKGROUND: The effect of anti-osteoporosis treatment in elderly patients with osteoporosis and lumbar discectomy and fusion (LIF) for lumbar degenerative diseases is not well known. OBJECTIVE: This study aimed to evaluate the effect of perioperative anti-osteoporosis treatment in the patients with osteoporosis and LIF. METHODS: From January to December 2022, patients were divided into three groups according to the inclusive criteria: the normal group (Group A), the osteopenia group (Group B) and the osteoporosis group (Group C). Quantitative computed tomography (QCT), height of the intervertebral space (HIS), segmental sagittal angle (SSA), visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were compared between the groups at the follow-up time. The serum Ca2 + , osteocalcin (OC), propeptide of type I procollagen (PINP) C-terminal cross-linking telopeptide of type I collagen (ß-CTX) and 25-OH vitamin D (25-OH VD) levels were compared between the groups at the time of follow-up. Interbody fusion was graded on the X-ray and CT images at the follow-up time. RESULTS: There were 165 patients in this study. There were significant differences in the mean age, mean score, HIS and SSA between the groups at the different follow-up times. There were significant differences in the concentrations of serum Ca2 + , OC, ß-CTX, 25-OH VD and PINP at the sixth month after surgery between the groups. There were significant differences in the concentrations of serum Ca2 + , ß-CTX and 25-OH VD between the pre-surgery and at six months after surgery in Group B and ß-CTX and 25-OH VD in Group C. There was a significant difference in the degree of fusion between Group B and C (χ2= 5.6243, P< 0.05). CONCLUSION: In elderly patients with LIF and osteoporosis, anti-osteoporosis therapy could reduce bone resorption and thus facilitate fusion. Anti-osteoporosis medication tends to enhance radiological, functional, and fusion short-term outcomes.
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Recent research on the water content of large igneous provinces (LIPs) has revealed that water has a significant impact on the formation of LIPs. However, most studies focus on the water content of mafic-ultramafic rocks, while relatively little attention has been paid to the water content of continental flood basalts (CFB), which form the major part of LIPs and are characterized by huge volumes (> 1 × 105 km3) and short eruption times. Here, we determined water contents of clinopyroxene crystals from the Akesu diabase, which is co-genetic with flood basalts of the Tarim LIP in China. Based on these measurements, we obtained a water content of higher than 1.23 ± 0.49 wt.% for the parental magma to the Tarim CFB and a minimum water content of 1230 ± 490 ppm for the mantle source, thus indicating the presence of a hydrous mantle plume. Combined with previous studies, our results suggest that water plays a key role in the formation of the Tarim LIP. Additionally, the whole-rock compositions of the Akesu diabase indicate a contribution of pyroxenite in the mantle source. This is consistent with a model, in which water was brought into the Tarim mantle plume by a subducted oceanic plate that entered the deep mantle.
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Asthma is a respiratory inflammatory disease, and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is involved in the progression of respiratory diseases. However, the role of NOX4 in asthma remains unclear. In the present study, we aimed to explore the effects of NOX4 on airway remodeling and inflammation. NOX4 expression was measured using immunocytochemistry (IHC), western blot, and real-time PCR (qPCR). Lung tissues were stained using the H&E assay. ELISA was used to examine the levels of airway remodeling-related indicators, and qPCR was used to detect airway inflammatory factors. The results indicated that NOX4 is highly expressed in lung tissues, bronchoalveolar lavage fluid (BALF), and serum of OVA-treated mice. Inhibition of NOX4 alleviated OVA-induced airway remodeling and inflammation. Similarly, TGF-ß1 was also upregulated in BALF and serum OVA-induced mice. Inhibition of TGF-ß1 signaling also improved airway remodeling and inflammation induced by OVA. Moreover, the downregulation of NOX4 inactivated the TGF-ß1-Smad2/3 pathway, and TGF-ß1 decreased Smad2/3 expression. Moreover, inhibition of the TGF-ß1 was enhanced, while TGF-ß1 reversed the effects on airway remodeling and inflammation induced by NOX4 inhibition. Taken together, the downregulation of NOX4 improves airway remodeling and inflammation via inactivation of the TGF-ß1-Smad2/3 pathway in asthma mice, suggesting that NOX4 may be a therapeutic target for asthma.
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Asma , NADPH Oxidasa 4 , Factor de Crecimiento Transformador beta1 , Animales , Ratones , Remodelación de las Vías Aéreas (Respiratorias) , Asma/metabolismo , Regulación hacia Abajo , Inflamación/inducido químicamente , Ovalbúmina/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , NADPH Oxidasa 4/genéticaRESUMEN
Objective: To investigate the effect of changing the normal appointment mode on day surgery. Methods: From December 2020 to December 2021, 302 patients with day surgery admitted to the hospital by using the unified reservation mode of the intelligent bed system were selected as the experimental group, while 302 patients with day surgery admitted to the hospital by using the decentralised bed reservation mode were randomly selected as the control group. The same-day surgery cancellation rate, bed utilisation rate and patient satisfaction were analysed and compared between the two groups. Results: The treatment experience of the patients in the experimental group was higher than that in the control group. The same-day surgery cancellation rate was lower than that of the control group, with a statistically significant difference (P < 0.05). Conclusion: The unified computer reservation mode of the intelligent bed reservation system is superior to the decentralised reservation mode across departments. A daytime intelligent bed reservation mode was adopted for unifying bed appointments, which could effectively reduce the same-day cancellation rate of day surgery, improve bed utilisation and improve patient satisfaction.
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Objective: To investigate the ultrasound characteristics and clinical efficacy of coronary arteries before and after immune blocking therapy with gamma globulin in children with Kawasaki disease. Methods: A total of 64 children with Kawasaki disease who were treated in our hospital from January 2018 to October 2021 were selected. All the children were given immune blocking therapy with gamma globulin on the basis of conventional treatment. The disappearance time of related symptoms and signs (fever, mucosal congestion, cervical lymphadenopathy, and swelling of the hands and feet) in children were counted. The white blood cell count (WBC), platelet count (PLT), C-reactive protein (CRP), and procalcitonin (PCT) levels of the children before and after treatment were compared, and the characteristics of coronary echocardiography before and after treatment were observed for analysis and discussion, to carefully observe whether the coronary artery involvement of the children was improved. Results: The inner diameter of the left and right coronary arteries significantly decreased (P < 0.05), and the levels of leukocytes, platelets, CRP, erythrocyte sedimentation rate, vascular endothelial growth factor (VEGF), and endostatin were significantly decreased compared with those before treatment, with a statistical difference (P < 0.05). Conclusion: The effect of gamma globulin in the treatment of Kawasaki disease is remarkable, which can improve the blood indexes, VEGF, and endostatin levels in children, significantly reduce coronary dilatation, and reduce the incidence of coronary artery disease. Echocardiography is of high value in the examination of children with Kawasaki disease, which can accurately detect the size, location, and inner diameter of coronary artery lesions, and can effectively evaluate the treatment effect on children.
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Background: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by progressive, destructive polyarthritis. However, the cause and underlying molecular events of RA are not clear. Here, we applied integrated bioinformatics to identify tissue-specific expressed hub genes involved in RA and reveal potential targeted drugs. Methods: Three expression profiles of human microarray datasets involving fibroblast-like synoviocytes (FLS) were downloaded from the Gene Expression Omnibus (GEO) database, the differentially expressed mRNAs (DEGs), miRNAs (DEMs), and lncRNAs (DELs) between normal and RA synovial samples were screened using GEO2R tool. BioGPS was used to identified tissue-specific expressed genes. Functional and pathway enrichment analyses were performed for common DEGs using the DAVID database, and the protein-protein interaction (PPI) network of common DEGs was constructed to recognize hub genes by the STRING database. Based on receiver operating characteristic (ROC) curve, we further investigated the prognostic values of tissue-specific expressed hub genes in RA patients. Connectivity Map (CMap) was run to identify novel anti-RA potential drugs. The DEM-DEG pairs and ceRNA network containing key DEMs were established by Cytoscape. Results: We obtain a total of 418 DEGs, 23 DEMs and 49 DELs. 64 DEGs were verified as tissue-specific expressed genes, most derive from the hematologic/immune system (20/64, 31.25%). GO term and KEGG pathway enrichment analysis showed that DEGs focused primarily on immune-related biological process and NF-κB pathway. 10 hub genes were generated via using MCODE plugin. Among them, SPAG5, CUX2, and THEMIS2 were identified as tissue-specific expressed hub genes, these 3 tissue-specific expressed hub genes have superior diagnostic value in the RA samples compared with osteoarthritis (OA) samples. 5 compounds (troleandomycin, levodopa, trichostatin A, LY-294002, and levamisole) rank among the top five in connectivity score. In addition, 5 miRNAs were identified to be key DEMs, the lncRNA-miRNA-mRNA network with five key DEMs was formed. The networks containing tissue-specific expressed hub genes are as follows: ARAP1-AS2/miR-20b-3p/TRIM3, ARAP1-AS2/miR-30c-3p/FRZB. Conclusion: This study indicates that screening for identify tissue-specific expressed hub genes and ceRNA network in RA using integrated bioinformatics analyses could help us understand the mechanism of development of RA. Besides, SPAG5 and THEMIS2 might be candidate biomarkers for diagnosis of RA. LY-294002, trichostatin A, and troleandomycin may be potential drugs for RA.
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BACKGROUND: The local anatomy of the lumbosacral region of spine is complicated, with special biomechanical characteristics. For surgical management of tuberculous spondylitis reported in the literature, the methods would be two-stage anterior and posterior approaches or one-stage anterior and posterior approach with patient's intraoperative position being changed. These types of surgery approaches would result in long operative duration and more intraoperative blood loss, and most important there is no coordination between anterior and posterior procedures. METHODS: The purpose of this study was to introduce a new procedure called in the lateral position single -stage combined anteriorposterior approaches for treatment of lumbosacral tuberculous spondylitis and to evaluate its preliminary surgical outcomes. Fifteen patients with lumbosacral tuberculous spondylitis who underwent single-stage anterior and posterior radical focal debridement and reconstruction in lateral position in our hospital from April 2005 to June 2012 were included in the study. There were 6 males and 9 females with the average age of 46.8 years. The tuberculous lesions involved the following regions: L3-4 in 5cases, L4-5 in 5 cases, L5-S1 in 2 cases, L4 in one case, and L5 in 2 cases. The assessment of surgical outcomes was conducted with clinical symptoms and radiological findings,including operative time, blood loss. deformity angle, Frankel grade and Kirkaldy-Willis evaluation. RESULTS: Operation posture: The right lateral position was used for 11 patients and the left lateral position was used for the remaining 4 patients. The average duration of operation for the 15 patients was 270 min. The average intraoperative blood loss was 1720 ml. The mean follow-up period was 4.2 years. There was no recurrence. The postoperative radiological findings showed that the interbody bone grafts were fixed without any dislodgment. There was significant difference between preoperative and postoperative lumbosacral lordotic angles. Kirkaldy-Willis classification rating for the 13 cases with satisfactory results. CONCLUSION: Single-stage combined anterior and posterior surgical management of lumbosacral tuberculous spondylitis with patient in lateral position can achieve radical focal debridement, anterior and posterior procedure coordination and spinal reconstruction.
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Fusión Vertebral , Tuberculosis de la Columna Vertebral , Pérdida de Sangre Quirúrgica , Femenino , Humanos , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Fusión Vertebral/métodos , Tuberculosis de la Columna Vertebral/cirugíaRESUMEN
This study investigated the effects of PGPs (Pleurotus geesteranus polysaccharides), a glucopyranose isolated from the mycelium of Pleurotus geesteranus and characterized with the main chain of â4)-α-D-Glcp-(1â, on the prevention against alcohol liver diseases (ALD), with the aim of providing a theoretical basis for the application of P. geesteranus as prebiotic agents in preventing and treating gut dysbiosis and alcohol-related metabolic disorders in individuals with ALD. The results showed that PGP treatment reduced oxidative stress by up-regulating the Nrf2/HO-1 signalling pathways, and decreased the pro-inflammatory factors by down-regulating TLR4/NF-κB signalling pathways. Furthermore, we validated effects of PGPs on balancing the gut-liver axis by maintaining the integrity of the intestinal epithelial barrier of decreasing intestinal permeability, increasing intestinal tight-junction protein and mucin expression and elevating the abundance of short-chain fatty acids (SCFAs) producers in the intestine by regulating the microbiota composition.
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Glucosa/farmacología , Hepatopatías Alcohólicas/prevención & control , Pleurotus , Polisacáridos/farmacología , Animales , Animales no Consanguíneos , Modelos Animales de Enfermedad , Microbioma Gastrointestinal/efectos de los fármacos , Glucosa/análogos & derivados , Glucosa/química , Masculino , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Polisacáridos/uso terapéutico , Receptor Toll-Like 4/metabolismoRESUMEN
Magmatic liquids, including silicate and carbonate melts, are principal agents of mass and heat transfer in the Earth and terrestrial planets, and they play a crucial role in various geodynamic processes and in Earth's evolution. Electrical conductivity data of these melts elucidate the cause of electrical anomalies in Earth's interior and shed light on the melt structure. With the improvement in high-pressure experimental techniques and theoretical simulations, major progress has been made on this front in the past several decades. This review aims to summarize recent advances in experimental and theoretical studies on the electrical conductivity of silicate and carbonate melts of different compositions and volatile contents under high temperature and pressure. The electrical conductivity of silicate melts depends strongly on temperature, pressure, water content and the ratio of non-bridging oxygens to tetrahedral cations (NBO/T). By contrast, the electrical conductivity of carbonate melts exhibits a weak dependence on temperature and pressure due to their fully depolymerized structure. The electrical conductivity of carbonate melts is higher than that of silicate melts by at least two orders of magnitude. Water can increase electrical conductivity significantly and reduce the activation energy of silicate melts. Conversely, this effect is weak for carbonate melts. In addition, the replacement of alkali-earth elements (Ca2+ or Mg2+) with alkali elements causes a significant decrease in the electrical conductivity of carbonate melts. A distinct compensation trend is revealed for the electrical conductivity of silicate and carbonate melts under anhydrous and hydrous conditions. Several important applications of laboratory-based melt conductivity are introduced in order to understand the origin of high-conductivity anomalies in the Earth's mantle. Perspectives for future studies are also provided.
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Hydrogen isotopes have been widely used as powerful tracers to understand the origin of terrestrial water and the water circulation between the surface and the deep interior of the Earth. However, further quantitative understanding is hindered due to a lack of observations about the changes in D/H ratios of a slab during subduction. Here, we report hydrogen isotope data of olivine-hosted melt inclusions from active volcanoes with variable depths (90â550 km) to the subducting Pacific slab. The results show that the D/H ratio of the slab fluid at the volcanic front is lower than that of the slab fluid just behind the volcanic front. This demonstrates that fluids with different D/H ratios were released from the crust and the underlying peridotite portions of the slab around the volcanic front. The results also show that the D/H ratios of slab fluids do not change significantly with slab depths from 300 to 550 km, which demonstrates that slab dehydration did not occur significantly beyond the arc. Our estimated δD value for the slab materials that accumulated in the mantle transition zone is > - 90, a value which is significantly higher than previous estimates.
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Objective Traditional breast ultrasound relies too much on the operation skills of diagnostic doctors, and the repeatability in different doctors was low. This study aimed to evaluate the assistant diagnostic value of S-Detect artificial intelligence (AI) system in differentiating benign from malignant breast masses. Methods The ultrasound images of 40 patients who underwent ultrasound examination in our hospital were collected. The conventional ultrasound images, elastic images, and S-Detect mode of breast lesions were analyzed. The breast imaging reporting and data system recommended by the American Society of Radiology (BI-RADS) classification for each breast mass was evaluated both by the doctor and AI. The receiver operator characteristics (ROC) curves were drawn to compare the diagnostic efficiency. Result Among the 40 lesions, 16 were benign, and 24 were malignant. The S-Detect AI system had a high diagnostic efficiency for malignant mass, with sensitivity, specificity, and accuracy of 95.8%, 93.8%, and 89.6%. The accuracy of AI was higher than the elastic image and then than the conventional gray-scale image. With the assistance of the S-Detect AI system, the accuracy of BI-RADS classification was improved significantly. Conclusion The S-Detect AI system will enhance breast cancer diagnostic accuracy and improve ultrasound examination quality.
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Neoplasias de la Mama , Inteligencia Artificial , Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Sensibilidad y Especificidad , Ultrasonografía MamariaRESUMEN
OBJECTIVE: Debate on the effectiveness of preoperative embolization for spinal metastatic lesions, especially for nonhypervascular tumors, has persisted. The present study aimed to identify the effectiveness of preoperative embolization in patients who had undergone surgery for spinal metastasis. METHODS: Two of us (Z.T. and Z.H.) independently searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases to identify eligible clinical studies that had compared the outcomes of patients treated surgically for spinal metastatic disease with or without preoperative embolization. The primary outcomes included intraoperative blood loss, perioperative blood loss, and transfusion requirements. The secondary outcomes include the operative time, overall survival, and complication rates. Meta-analyses were performed for subgroups of hypervascular, nonhypervascular, and mixed tumors. A fixed effects model was applied when I2 was <50%, and a random effects model was applied when I2 was >50%. RESULTS: A total of 12 studies (1 randomized controlled trial and 11 retrospective case-control studies), with 744 patients, were included. Significantly less intraoperative blood loss (mean difference [MD], -1171.49 mL; 95% confidence interval [CI], -2283.10 to -59.88; P = 0.039), fewer blood transfusions (MD, -3.13 U; 95% CI, -4.86 to -1.39; P < 0.001), and shorter operative times (MD, -33.91 minutes; 95% CI, -59.65 to -8.17; P = 0.010) were identified for the embolization group in the hypervascular subgroup. In the nonhypervascular and mixed tumor subgroups, no differences in effectiveness were identified in blood loss, transfusion requirement, or operative time when stratified by the use of embolization. The overall survival and complication rates were similar between the embolization and nonembolization groups in each subgroup. CONCLUSIONS: The current data support the use of preoperative embolization for hypervascular metastatic tumors to the spine. However, little evidence is available to support the use of preoperative embolization for nonhypervascular metastatic tumors to the spine.
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Embolización Terapéutica/métodos , Procedimientos Neuroquirúrgicos/métodos , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Columna Vertebral/cirugía , Humanos , Cuidados PreoperatoriosRESUMEN
BACKGROUND: Psoriatic arthritis (PsA) is inflammatory arthritis associated with psoriasis, which involves the axial joint and the distal interphalangeal joints. Its clinical features are varied, often resulting in delayed diagnosis and treatment. Improved knowledge about disease mechanisms will catalyze the rapid development of effective targeted therapies for this disease. The perturbations in the gene co-expression network may not be detected by the differential expression analysis of the microarray. This study aims to identify key modules and hub genes in psoriatic arthritis-applied WGCNA (weighted gene co-expression network analysis) on a microarray. METHODS: This study downloaded the array data of GSE61281 from the gene expression overview (GEO) database, which includes 20 psoriatic arthritis samples and 12 healthy controls. The analysis was performed with the WGCNA package. Gene ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these key modules. Candidate hub genes were identified using GS and MM measures, Cytoscape, and the online database STRING. RESULTS: A total of 10 co-expression modules were constructed. The lightcyan module was identified as the key module. GO and KEGG pathway analyses were mainly enriched in dephosphorylation, regulation of small GTPase-mediated signal transduction, Ras signaling pathway, MAPK signaling pathway, and vascular smooth muscle contraction. Two hub genes, RHOH/TRAF1, were selected. CONCLUSIONS: This finding may indicate that RHOH/TRAF1 play a critical role in the pathogenesis of PsA. This is one of the first studies in PsA using WGCNA, which may provide a new research direction for further understanding of the molecular mechanism and clinical application of PsA. Key points ⢠The WGCNA method was applied to the expression profile microarray of psoriatic arthritis and the co-expression module was constructed. ⢠Identify the key modules by combining the onset time of psoriasis in patients with psoriatic arthritis. ⢠Three screening methods are used to identify and verify hub genes of key modules.
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Artritis Psoriásica , Artritis Psoriásica/genética , Perfilación de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , Humanos , Factor 1 Asociado a Receptor de TNF , Factores de Transcripción , Proteínas de Unión al GTP rhoRESUMEN
Angiogenesis is essential for bone formation during skeletal development. HIF-1α and the HIF-responsive gene VEGF (vascular endothelial growth factor) are reported to be a key mechanism for coupling osteogenesis and angiogenesis. Salidroside (SAL), a major biologically active compound of Rhodiola rosea L., possesses diverse pharmacological effects. However, whether SAL can protect against bone loss via the HIF-1α/VEGF pathway, specifically by inducing angiogenesis-osteogenesis coupling in vivo, remains unknown. Therefore, in the present study, we employed primary human umbilical vein endothelial cells (HUVECs) and the permanent EA.hy926 human endothelial cell line to determine the cellular and molecular effects of SAL on vascular endothelial cells and the HIF-1α-VEGF signalling pathway in the coupling of angiogenesis-osteogenesis. The in vitro study revealed that the HUVECs and EA.hy926 cells treated with conditioned medium from osteoblast cells (MG-63 cells) treated with SAL or treated directly with SAL showed enhanced proliferation, migration and capillary structure formation. However, supplementation with an anti-VEGF antibody during the treatment of endothelial cells (ECs) significantly reversed the pro-angiogenic effect of SAL. Moreover, SAL upregulated HIF-1α expression and increased its transcriptional activity, consequently upregulating VEGF expression at the mRNA and protein levels. In addition, our in vivo analysis demonstrated that SAL can stimulate endothelial sprouting from metatarsal bones. Thus, our mechanistic study demonstrated that the pro-angiogenic effects of SAL involve HIF-1α-VEGF signalling by coordinating the coupling of angiogenesis-osteogenesis in the bone environment. Therefore, we have discovered an ideal molecule that simultaneously enhances angiogenesis and osteogenesis and thereby accelerates bone healing.
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Glucósidos/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Huesos Metatarsianos/irrigación sanguínea , Neovascularización Fisiológica/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Comunicación Paracrina , Fenoles/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Microambiente Celular , Medios de Cultivo Condicionados/metabolismo , Femenino , Curación de Fractura/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Ratones Endogámicos BALB C , Osteoblastos/metabolismo , Embarazo , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
BACKGROUND: Acute mountain sickness has become a heavily researched topic in recent years. However, the genetic mechanism and effects have not been elucidated. Our goal is to construct a gene co-expression network to identify the key modules and hub genes associated with high altitude hypoxia. RESULTS: The GSE46480 dataset of rapidly transported healthy adults with acute mountain sickness was selected and analyzed by weighted gene co-expression network analysis (WGCNA) to construct a co-expression network. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the data set were carried out using Database for Annotation Visualization and Integrated Discovery (DAVID), and the hub genes were selected. We found that the turquoise module was most significantly correlated with acute mountain sickness. The functional enrichment analysis showed that the turquoise module was related to the apoptotic process, protein transport, and translation processes. The metabolic pathway analysis identified hsa03010:ribosome and hsa04144:endocytosis as the most important pathways in the turquoise module. Ten top 10 hub genes (MRPL3, PSMC6, AIMP1, HAT1, DPY30, ATP5L, COX7B, UQCRB, DPM1, and COMMD6) for acute mountain sickness were identified. CONCLUSION: One module and 10 hub genes were identified, which were related to acute mountain sickness. The reference provided by this module may help to elucidate the mechanism of acute mountain sickness. In addition, the hub genes may be used in the future as a biomarker and therapeutic target for accurate diagnosis and treatment.
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Mal de Altura/genética , Redes Reguladoras de Genes , Adulto , Femenino , Expresión Génica , Ontología de Genes , Humanos , Masculino , Redes y Vías Metabólicas , Persona de Mediana EdadRESUMEN
BACKGROUND: This study aims to investigate the relationship between serum uric acid (SUA) and the severity of diabetic nephropathy (DN) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 2961 patients were enrolled in the present cross-sectional study. The severity of DN was determined by 24-hour urinary albumin excretion (UAE), which was classified as normal (UAE <30 mg/24 h), microalbuminuria (UAE: 30-299 mg/24 h), and macroalbuminuria (≥300 mg/24 h). The severity of DR was determined by non-mydriatic retinal photography and was classified as non-diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative DR (PDR). RESULTS: Patients with high SUA levels (≥420 µmol/L for males and ≥360 µmol/L for females) had a significantly higher prevalence of DN (UAE ≥30 mg/24 h, 39.3% vs 26.3%; p < 0.001), higher UAE levels (140 ± 297 vs 63 ± 175 mg/24 h; p < 0.001), and lower estimated glomerular filtration rate (eGFR; 79.3 ± 26.8 vs 96.8 ± 19.6 mL/min/1.73 m; p < 0.001), when compared with patients with normal SUA levels. However, the prevalence of DR, NPDR, or PDR did not differ. Furthermore, the concentration of SUA was higher in patients with higher severity of DN (all, p < 0.001) and patients with PDR (compared with NDR or NPDR, p < 0.05). SUA levels were positively associated with male gender, body mass index, the use of diuretics, triglyceride, low-density lipoprotein, and UAE levels, whereas they were negatively correlated with high-density lipoprotein, fasting blood glucose, glycosylated hemoglobin, and eGFR. After adjustment, SUA remained significantly associated with UAE (r = 0.069, p < 0.001). CONCLUSION: For patients with T2DM, higher SUA levels are associated with higher UAE, lower eGFR, and higher prevalence of DN, but not DR.
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Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/etiología , Retinopatía Diabética/etiología , Ácido Úrico/sangre , Anciano , Estudios Transversales , Nefropatías Diabéticas/sangre , Retinopatía Diabética/sangre , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Studies on the model plant Arabidopsis thaliana have uncovered the identities of most enzymatic components involved in seed storage lipid biosynthesis. However, much remains to be learned on how pathway interactions operate in the seed metabolic network. In this study, we dissected seed glycerolipid molecular compositional changes in the Arabidopsis mutant deficient in diacylglycerol acyltransferase 1 (DGAT1). Our results indicate that metabolic adjustments occurred in both phosphatidylcholine synthesis and deacylation in developing seeds. Ultrastructural changes of perturbed oil and protein bodies were also evident in cotyledon parenchyma cells. To unmask the physiological and developmental role associated with DGAT1-mediated neutral lipid biosynthesis, we attempted to combine dgat1 mutation with lpcat2 that harbors a defect in lysophosphatidylcholine acyltransferase 2 (LPCAT2). Disruption in both DGAT1 and LPCAT2 led to an apparent defect in pollen development that manifested as pollen sterility. Collectively, our results highlight a role of DGAT1 in both storage lipid synthesis and plant development.
Asunto(s)
Aciltransferasas/genética , Proteínas de Arabidopsis/genética , Diacilglicerol O-Acetiltransferasa/genética , Desarrollo de la Planta/genética , Arabidopsis/enzimología , Arabidopsis/crecimiento & desarrollo , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Redes y Vías Metabólicas/genética , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Semillas/genética , Semillas/crecimiento & desarrollo , Triglicéridos/genética , Triglicéridos/metabolismoRESUMEN
Global correlations of mid-ocean-ridges basalt chemistry, axial depth and crustal thickness have been ascribed to mantle temperature variations affecting degree of melting. However, mantle H2O content and elemental composition may also play a role. How H2O is distributed in the oceanic upper mantle remains poorly constrained. We tackled this problem by determining the H2O content of orthopyroxenes (opx) and clinopyroxenes (cpx) of peridotites from a continuous lithospheric section created during 26 Ma at a 11°N Mid-Atlantic Ridge segment, and exposed along the Vema Transform. The H2O content of opx ranges from 119 ppm to 383 ppm; that of cpx from 407 ppm to 1072 ppm. We found anomalous H2O-enriched peridotites with their H2O content not correlating inversely with their degree of melting, although H2O is assumed to be incompatible during melting. Inverse correlation of H2O with Ce, another highly incompatible component, suggests post-melting H2O enrichment. We attribute a major role to post-melting temperature-dependent diffusion of hydrogen occurring above the melting region, where water-rich melt flows faster than residual peridotites through dunitic conduits cross-cutting the uprising mantle. Accordingly, estimates of the H2O content of the MORB mantle source based on H2O in abyssal peridotites can be affected by strong uncertainties.
RESUMEN
Magmatism at some intraplate volcanoes and large igneous provinces (LIPs) in continental areas may originate from hydrous mantle upwelling (i.e. a plume) from the mantle transition zone (MTZ) at 410-660 km depths in the Earth's deep interior. However, the ultimate origin of the magmatism, i.e. why mantle plumes could have been generated at the MTZ, remains unclear. Here, we study the buoyancy of a plume by investigating basalts from the Changbaishan volcano, beneath which a mantle plume from the hydrous MTZ is observed via seismology. Based on carefully determined water contents of the basalts, the potential temperature of the source mantle is estimated to be 1310-1400 °C, which is within the range of the normal upper mantle temperature. This observation suggests that the mantle plume did not have a significant excess heat, and that the plume upwelled because of buoyancy resulting from water supplied from the Pacific slab in the MTZ. Such a hydrous mantle plume can account for the formation of extremely hydrous LIP magmatism. The water was originally sourced from a stagnant slab and stored in the MTZ, and then upwelled irrespective of the presence or absence of a deep thermal plume.