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1.
Theriogenology ; 195: 103-114, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36332369

RESUMO

Oxidative stress is a common cause of male infertility. Sertoli cells are one of the target cells of oxidative injury, which leads to impaired testicular function. Follicle-stimulating hormone (FSH) is critical in Sertoli cell function. However, the role of FSH in the response of goat Sertoli cells to H2O2-induced oxidative stress has not been studied yet. To investigate this response, we established an oxidative stress model using goat Sertoli cells. FSH pretreatment significantly enhanced the decreased cell viability (p < 0.05) caused by oxidative injury and inhibited autophagic flux. FSH significantly increased p62 mRNA and protein levels (p < 0.01). Further investigations revealed that FSH also increased the expression level and nuclear translocation of Nrf2 in Sertoli cells (p < 0.01), which resulted in increased antioxidant enzyme activity (p < 0.05). In contrast, treatment with siNrf2 and sip62 abolished this protective effect of FSH. These findings suggest that FSH protects Sertoli cells against oxidative stress via the p62-Nrf2 pathway, and that p62 accumulation maintains persistent activation of Nrf2. Thus, p62 and Nrf2 are required for FSH-mediated protective role in H2O2-induced Sertoli cell injury. The findings reveal new mechanisms by which FSH protects against oxidative injury in goat Sertoli cells.


Assuntos
Fator 2 Relacionado a NF-E2 , Células de Sertoli , Masculino , Animais , Fator 2 Relacionado a NF-E2/genética , Hormônio Foliculoestimulante/farmacologia , Cabras , Peróxido de Hidrogênio/toxicidade , Estresse Oxidativo , Autofagia , Antioxidantes
2.
J Environ Sci (China) ; 124: 513-521, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36182160

RESUMO

Over the past decade, the emission standards and fuel standards in Beijing have been upgraded twice, and the vehicle structure has been improved by accelerating the elimination of 2.95 million old vehicles. Through the formulation and implementation of these policies, the emissions of carbon monoxide (CO), volatile organic compounds (VOCs), nitrogen oxides (NOx), and fine particulate matter (PM2.5) in 2019 were 147.9, 25.3, 43.4, and 0.91 kton in Beijing, respectively. The emission factor method was adopted to better understand the emissions characteristics of primary air pollutants from combustion engine vehicles and to improve pollution control. In combination with the air quality improvement goals and the status of social and economic development during the 14th Five-Year Plan period in Beijing, different vehicle pollution control scenarios were established, and emissions reductions were projected. The results show that the emissions of four air pollutants (CO, VOCs, NOx, and PM2.5) from vehicles in Beijing decreased by an average of 68% in 2019, compared to their levels in 2009. The contribution of NOx emissions from diesel vehicles increased from 35% in 2009 to 56% in 2019, which indicated that clean and energy-saving diesel vehicle fleets should be further improved. Electric vehicle adoption could be an important measure to reduce pollutant emissions. With the further upgrading of vehicle structure and the adoption of electric vehicles, it is expected that the total emissions of the four vehicle pollutants can be reduced by 20%-41% by the end of the 14th Five-Year Plan period.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Pequim , Monóxido de Carbono/análise , China , Monitoramento Ambiental , Óxidos de Nitrogênio/análise , Material Particulado/análise , Emissões de Veículos/análise , Compostos Orgânicos Voláteis/análise
3.
J Colloid Interface Sci ; 630(Pt A): 544-555, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36270175

RESUMO

Efforts to develop a green, inexpensive and effective adsorbent are crucial for eliminating antibiotics in polluted water. The sorption capacity of the as-prepared polyvinyl alcohol (PVA)-assisted cellulose nanocrystals/SiO2 (CNCs/SiO2) composite aerogel to ciprofloxacin (CIP) rises with the increase of temperature and initial concentration. Reverse trend of sorption capacity can be found when increasing the adsorbent dosage of adsorbent. The optimal pH value for the sorption is proved to be 4. It's found in the uniaxial compression test that the maximum load that PVA-assisted aerogels can withstand is nearly 100 times than that of non-PVA aerogels. Sorption results confirm that the Pseudo-second order (R2 = 0.9885) and Langmuir models (R2 = 0.9959) fit well to sorption kinetics and equilibrium data, respectively. The rate constant differs from the initial concentration of CIP according to the Pseudo-second order model. The composite aerogel sorption capacity of Langmuir (qmax) for CIP was 163.34 mg·g-1. The thermodynamic studies showed that the sorption process is endothermic with the value of enthalpy change of 41.032 kJ/mol. Hydrogen bonding, π-π interaction, hydrophobic and electrostatic interactions are the dominant mechanisms of CIP sorption by the PVA-assisted CNCs/SiO2 composite aerogel.


Assuntos
Ciprofloxacina , Álcool de Polivinil , Ciprofloxacina/química , Álcool de Polivinil/química , Dióxido de Silício/química , Adsorção , Cinética , Concentração de Íons de Hidrogênio
4.
Bioresour Technol ; 367: 128206, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36323371

RESUMO

Granule formation, microstructure and microbial spatial distribution are crucial to granule stability and nitrogen removal. Here, an upflow blanket filter (UBF) reactor with porous fixed cylinder carriers was fabricated and operated for 234 days to investigate overall performance and the formation mechanism of anammox granules. Results showed that the UBF performed the highest nitrogen removal efficiency of 93.19 ± 3.39% under nitrogen loading rate of 3.6 kg-N/m3/d and HRT of 2 h. The tryptophan-like proteins as the key component in EPS were vital for granules formation. Further 16 s rRNA analysis indicated that SBR1031 with a relative abundance of 40.5% played an important role in cell aggregation. Thus, anammox granules were developed successfully with a two-layered spatial structure where outer-layer was ammonia oxidizing bacteria and inner-core was anaerobic ammonia oxidizing bacteria. Together, introduction of porous fixed cylinder carriers is a valid method to avoid biomass loss and floatation.


Assuntos
Nitrogênio , Águas Residuárias , Reatores Biológicos/microbiologia , Esgotos/microbiologia , Amônia , Oxidação Anaeróbia da Amônia , Oxirredução
5.
Sci Total Environ ; 856(Pt 1): 158795, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36115405

RESUMO

Simultaneous removal of ammonium and nitrate was achieved in a methane-fed moving bed biofilm reactor (MBBR). In the reactor, methanotrophic microorganisms oxidized methane under hypoxic conditions likely to methanol, hence providing an electron donor to denitrifiers to reduce nitrate to nitrite that then allowed anaerobic ammonium oxidizing bacteria (Anammox) to remove excess ammonium as N2. The ammonium and nitrate removal rates reached 72.09 ± 5.81 mgNH4+-N/L/d and 62.61 ± 4.17 mgNO3--N/L/d when the MBBR was operated in continuous mode. Nitrate removal by the methane-fed mixed consortia was confirmed in a batch test revealing a CH4/NO3- molar removal ratio of 1.15. The functional populations were unveiled by FISH analysis and 16S rRNA gene sequencing, which showed that the biofilm was dominated by Anammox bacteria (Candidatus Kuenenia) and diverse taxa associated with the capacity for denitrification: aerobic methanotrophs (Methylobacter, Methylomonas, and unclassified Methylococcaceae), methylotrophic denitrifiers (Opitutaceae and Methylophilaceae), and other heterotrophic denitrifiers (Ignavibacteriaceae, Anaerolineaceae, Comamonadaceae, Rhodocyclaceae and Thauera). Neither DAMO archaea nor DAMO bacteria were found in the sequencing analysis, indicating that more unknown community members possess the metabolic capacity of methanotrophic denitrification.


Assuntos
Compostos de Amônio , Methylococcaceae , Desnitrificação , Nitrogênio/metabolismo , Biofilmes , Nitratos/metabolismo , Reatores Biológicos/microbiologia , Anaerobiose , RNA Ribossômico 16S , Compostos de Amônio/metabolismo , Metano/metabolismo , Methylococcaceae/metabolismo , Bactérias Anaeróbias/metabolismo , Bactérias/metabolismo , Oxirredução
6.
Nucleic Acids Res ; 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36318264

RESUMO

Super-enhancers (SEs) are cell-specific DNA cis-regulatory elements that can supervise the transcriptional regulation processes of downstream genes. SEdb 2.0 (http://www.licpathway.net/sedb) aims to provide a comprehensive SE resource and annotate their potential roles in gene transcriptions. Compared with SEdb 1.0, we have made the following improvements: (i) Newly added the mouse SEs and expanded the scale of human SEs. SEdb 2.0 contained 1 167 518 SEs from 1739 human H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) samples and 550 226 SEs from 931 mouse H3K27ac ChIP-seq samples, which was five times that of SEdb 1.0. (ii) Newly added transcription factor binding sites (TFBSs) in SEs identified by TF motifs and TF ChIP-seq data. (iii) Added comprehensive (epi)genetic annotations of SEs, including chromatin accessibility regions, methylation sites, chromatin interaction regions and topologically associating domains (TADs). (iv) Newly embedded and updated search and analysis tools, including 'Search SE by TF-based', 'Differential-Overlapping-SE analysis' and 'SE-based TF-Gene analysis'. (v) Newly provided quality control (QC) metrics for ChIP-seq processing. In summary, SEdb 2.0 is a comprehensive update of SEdb 1.0, which curates more SEs and annotation information than SEdb 1.0. SEdb 2.0 provides a friendly platform for researchers to more comprehensively clarify the important role of SEs in the biological process.

7.
Rev Sci Instrum ; 93(10): 103903, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319315

RESUMO

M-STAR is a next generation polarized neutron reflectometer with advanced capabilities. A new focusing guide concept is optimized for samples with dimensions down to a millimeter range. A proposed hybrid pulse-skipping chopper will enable experiments at constant geometry at one incident angle in a broad range of wavevector transfer Q up to 0.3 A-1 for specular, off-specular, and GISANS measurements. M-STAR will empower nanoscience and spintronics studies routinely on small samples (∼2 × 2 mm2) and of atomic-scale thickness using versatile experimental conditions of magnetic and/or electric fields, light, and temperature applied in situ to novel complex device-like nanosystems with multiple buried interfaces. M-STAR will enable improved grazing incidence diffraction measurements, as a surface-sensitive depth-resolved probe of, e.g., the out-of-plane component of atomic magnetic moments in ferromagnetic, antiferromagnetic, and more complex structures as well as in-plane atomic-scale structures inaccessible with contemporary diffractometry and reflectometry. New horizons will be opened by the development of an option to probe near-surface dynamics with inelastic grazing incidence scattering in the time-of-flight mode. These novel options in combination with ideally matched parameters of the second target station will place M-STAR in the world's leading position for high resolution polarized reflectometry.

8.
Ann Transl Med ; 10(19): 1069, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36330384

RESUMO

Background: Roxadustat is a newly marketed hypoxia-inducible factor prolyl hydroxylase inhibitor used to treat anemia in patients with end-stage renal disease (ESRD). While clinical trials have demonstrated the therapeutic effects of roxadustat in patients with ESRD who are resistant to erythropoiesis-stimulating agents (ESAs), its metabolic effects are still unclear. Methods: Thirty-two individuals with ESRD and ESA resistance from the Blood Purification Center of Dalian Municipal Central Hospital were included. A total of 96 fasting serum samples were obtained from participants before treatment with roxadustat, and after treatment for 15 and 30 days. Ultra-high performance liquid chromatography-mass spectrometry-based metabolomics and lipidomics strategies were applied to investigate the effects of roxadustat on serum metabolism. Results: A total of 255 metabolites and 444 lipid molecular species were detected and quantified. Sphingolipids and phospholipids decreased significantly during treatment, possibly associated with changes in phospholipid and ceramide metabolism. Bile acid levels decreased and cholic acid/chenodeoxycholic acid increased, indicating changes in gut microbiota and bile acid metabolism. Amino acids also changed during the process of treatment. Conclusions: The present study showed sphingolipids, phospholipids, and bile acids were significantly altered, which may be associated with a changed metabolism caused by roxadustat. This approach provided a powerful tool for exploring the mechanisms of ESA resistance in ESRD patients and may represent a promising strategy for elucidating the complex therapeutic mechanisms of other drugs.

9.
Opt Express ; 30(23): 42086-42096, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36366669

RESUMO

Different signal representations show different unique features for classification. In this paper, a feature fusion method with attention mechanism based on multiple signal representations is proposed for Φ-OTDR event classification with buried optical fiber. Each signal representation is fused after feature extraction to get richer and better features. With the help of a layer pruning method based on attention mechanism, the network size can be kept and avoid computation increase. Experiment results show that this method with 3 signal representations can improve the recognition accuracy to 97.93%, with 3.52% improvement compared to single representation approach. It also shows higher recognition accuracy than the tradition multiple signal representations fusion methods at the input stage. Furthermore, when it is used to fuse four representations, the recognition accuracy can be further improved to 99.11%.

10.
Metabolites ; 12(11)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36355164

RESUMO

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex disorder that is implicated in dysregulations in multiple biological pathways, orchestrated by interactions between genetic predisposition, metabolic syndromes and environmental factors. The limited knowledge of its pathogenesis is one of the bottlenecks in the development of prognostic and therapeutic options for MAFLD. Moreover, the extent to which metabolic pathways are altered due to ongoing hepatic steatosis, inflammation and fibrosis and subsequent liver damage remains unclear. To uncover potential MAFLD pathogenesis in humans, we employed an untargeted nuclear magnetic resonance (NMR) spectroscopy- and high-resolution mass spectrometry (HRMS)-based multiplatform approach combined with a computational multiblock omics framework to characterize the plasma metabolomes and lipidomes of obese patients without (n = 19) or with liver biopsy confirmed MAFLD (n = 63). Metabolite features associated with MAFLD were identified using a metabolome-wide association study pipeline that tested for the relationships between feature responses and MAFLD. A metabolic pathway enrichment analysis revealed 16 pathways associated with MAFLD and highlighted pathway changes, including amino acid metabolism, bile acid metabolism, carnitine shuttle, fatty acid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and steroid metabolism. These results suggested that there were alterations in energy metabolism, specifically amino acid and lipid metabolism, and pointed to the pathways being implicated in alerted liver function, mitochondrial dysfunctions and immune system disorders, which have previously been linked to MAFLD in human and animal studies. Together, this study revealed specific metabolic alterations associated with MAFLD and supported the idea that MAFLD is fundamentally a metabolism-related disorder, thereby providing new perspectives for diagnostic and therapeutic strategies.

11.
Open Med (Wars) ; 17(1): 1682-1698, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36349193

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignancies that have a poor prognosis. Necroptosis has been demonstrated in recent years to be a form of inflammatory cell death occurring in multicellular organism, which plays complex roles in cancer. However, the expression of necroptosis-related miRNAs and genes in HNSCC and their correlations with prognosis remain unclear. In this study, R software was used to screen differentially expressed miRNAs downloaded from The Cancer Genome Atlas. A prognostic model containing six necroptosis-related miRNAs (miR-141-3p, miR-148a-3p, miR-331-3p, miR-543, miR-425-5p, and miR-7-5p) was generated, whose risk score was validated as an independent prognostic factor for HNSCC. Target genes of the key miRNAs were obtained from TargetScan, miRDB, and miRTarBase, and 193 genes in the intersection of the three databases were defined as consensus genes. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses indicated that the composition of the tumor microenvironment as well as specific pathways may be closely related to necroptosis in HNSCC. Nine key genes were also obtained by the MCODE and cytoHubba plug-ins of Cytoscape: PIK3CD, NRAS, PTK2, IRS2, IRS1, PARP1, KLF4, SMAD2, and DNMT1. A prognostic model formed by the key gene was also established, which can efficiently predict the overall survival of HNSCC patients. In conclusion, necroptosis-related miRNAs and genes play important roles in tumor development and metastasis and can be used to predict the prognosis of HNSCC.

12.
J Pain Res ; 15: 3563-3573, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36394059

RESUMO

Objective: To investigate the differences, correlations, and clinical significance of the paraspinal muscles among patients with isthmic spondylolisthesis (IS), degenerative lumbar spondylolisthesis (DLS), and age-matched healthy subjects. Methods: This study involved 159 age-matched patients with L4 anterior spondylolisthesis. The patients were divided into the IS group (n = 81) and DLS group (n = 78). Eighty-four age-matched healthy adults were enrolled as the control group. The cross-sectional area (CSA) of paraspinal muscles (multifidus [MF], erector spinae [ES], and psoas [PS]) and the relative CSA of the paraspinal muscles (paraspinal muscle CSA/vertebral CSA) were measured in the IS group, DLS group, and control group. The degree of fat infiltration was simultaneously observed. Results: There was no significant difference in age or sex among the three groups. The relative CSA of the MF and PS was higher in control group than in IS and DLS groups (p < 0.05). The relative CSA of ES was higher in IS and control groups than in DLS group (p < 0.05). The relative CSA of total paraspinal muscles decreased in the order of control group > IS group > DLS group (p < 0.05). Logistic regression analysis showed that the relative CSA of MF, and the degree of fat infiltration of ES were independent protective factors for IS (odds ratio < 1, p < 0.05). The relative CSA of MF was an independent protective factor for DLS (odds ratio < 1, p < 0.05), whereas BMI and the degree of fat infiltration of MF were independent risk factor for DLS (odds ratio > 1, p < 0.05). Conclusion: Compared with the control group, patients with IS and DLS showed varying degrees of degeneration, and the degree of degeneration in patients with DLS was more severe at the same age. Lower fat infiltration and higher paraspinal muscle CSA are protective factors for IS and DLS, whereas the higher BMI is risk factor for DLS.

13.
Artigo em Inglês | MEDLINE | ID: mdl-36360765

RESUMO

Older people in China have a poor understanding of hospital signage. To address this problem, in this study, we combined the theories of situated cognition and cognitive commonness in order to introduce the three main factors that affect the generation of situational cognitive commonness: composition of the situation, familiarity, and concreteness. We used these theories to construct a methodological framework for the design of geriatric hospital wayfinding signs that were based on situational cognitive commonness. The design of nine healthcare signs for Chinese national standards were used as examples in the study. First, users who were familiar with medical scenarios were asked to draw concrete cognitive conception graphics for the purposes of individual wayfinding targets from both physical and social situations. Next, we coded and grouped the generated graphics based on their situational features in order to extract groups of representative common graphics. Finally, we reorganized the common graphics and developed concrete designs, which were tested by the judgment test. The wayfinding signs designed according to the methodological framework of this study effectively improved the understanding of hospital signage among older Chinese people. This study took geriatric hospital wayfinding signs as the examples to provide a feasible theoretical basis and research reference for symbol design.


Assuntos
Diretórios de Sinalização e Localização , Humanos , Idoso , Instalações de Saúde , Hospitais , Cognição , China
14.
J Orthop Surg Res ; 17(1): 475, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329488

RESUMO

OBJECTIVES: To identify age-related radiographic risk factors for degenerative lumbar spinal stenosis (DLSS) and analyze correlations among them. METHODS: A total of 180 cases were enrolled in this study, and lumbar magnetic resonance was performed. Among them, 93 cases suffered DLSS and lumbar dynamic X-ray was examined. And following parameters were measured and evaluated: intervertebral disk height (IDH), the ratio of IDH(IDHL4-5/L3-4), initial IDH of L4-5(iIDHL4-5) in the DLSS group, disk degeneration (DD), cartilaginous endplate failure (CEF), Modic changes, the thickness of ligamentum flavum (LF), range of intervertebral motion (ROM), facet joint opening (FJO), facet joint angle (FJA), the standard cross-sectional area (SCSA) of the multifidus, erector spinae, and psoas major muscles. The data of two groups were compared, and the possible risk factors of DLSS were analyzed. RESULTS: Compared with the control group, the DLSS group had higher IDH except for L4-5 and larger iIDHL4-5 (P < 0.05). Significant differences were shown in CEF and the thickness of LF at L1-S1 and DD at L4-5 (P < 0.05). The DLSS group had smaller SCSA of multifidus, erector spinae, and psoas major muscles but greater FJA, FJO (P < 0.05). And the risk of DLSS increased when iIDHL4-5 ≥ 10.73 mm, FJA ≥ 52.03° , or FJO ≥ 3.75 mm. IDH positively correlated with SCSA of multifidus and psoas major muscles and ROM at L1-S1 (P < 0.05). DD showed negative linear relations with SCSA of multifidus and psoas muscle and positive linear relation with CEF at L1-2, L2-3, and L5-S1 (P < 0.05). CONCLUSION: Larger initial disk height and excessive CEF may induce DLSS by increasing intervertebral mobility to promote DD, and atrophied paravertebral muscles by weakening the stability of lumbar spine.


Assuntos
Degeneração do Disco Intervertebral , Estenose Espinal , Humanos , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/etiologia , Degeneração do Disco Intervertebral/patologia , Região Lombossacral/patologia , Músculos Paraespinais/patologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética
15.
Front Bioeng Biotechnol ; 10: 1031986, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338113

RESUMO

Metal-organic frameworks (MOFs) are a class of hybrid porous crystalline materials that are assembled with metal ions/clusters and organic linkers. The fungibility of organic ligands and metal centers endow MOFs that are easy to design and synthesize. Based on their unique structure, multifarious MOFs with diverse functionalities have recently been widely applied in various research areas. Particularly striking is the application of photo-responsive MOFs in biological sensing and imaging. Notably, the photoelectronic properties make photo-responsive MOFs an ideal platform for cancer phototherapy. Moreover, ultrahigh porosities and tunable pore sizes allow MOFs to load anticancer drugs, further enhancing the antitumor efficiency. In this review, the categories and developing strategies of MOFs are briefly introduced. The application fields of MOFs in bioimaging, such as up-conversion fluorescence imaging, single/two-photon fluorescence bioimaging, magnetic resonance imaging, etc., are summarized. The working mechanism of MOFs in photo-responsive, photothermal therapy (PTT), and photodynamic therapy (PDT) are expounded. Examples of using MOFs for cancer treatment, including PTT, PDT, chemotherapy, and radiotherapy, are also demonstrated. Lastly, current limitations, challenges, and future perspectives for bioimaging and cancer treatment of MOFs are discussed. We believe that the versatile MOF will bring the dawn to the next generation of cancer treatment.

16.
Cell Death Dis ; 13(11): 935, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344502

RESUMO

Osteosarcomas (OS) are highly metastatic and usually lead to poor outcomes. Epithelial-mesenchymal transition (EMT) is reported to be a critical event in metastasis. SIRT2 exerts dual functions in many different tumors. However, the underlying molecular mechanisms of SIRT2 in osteosarcoma cell metastasis and the question of whether SIRT2 regulates EMT have not been fully explored. In this study, we confirmed that SIRT2 was highly-expressed in human osteosarcoma MG63 and Saos-2 cell lines. The viability, migration and invasion of osteosarcoma cells were inhibited by knockdown of SIRT2 and were enhanced by overexpression of SIRT2. Moreover, SIRT2 positively regulated EMT and upregulated the protein levels of the mesenchymal markers N-cadherin and Vimentin and the levels of MMP2 and MMP9. A xenograft mouse model showed that SIRT2 knockdown in osteosarcoma cells led to reduced tumor growth, decreased expression of mesenchymal markers and impaired lung and liver metastasis in vivo. Furthermore, we showed that SIRT2 interacted with and upregulated the protein level of the EMT-associated transcription factor Snail. SIRT2 inhibited Snail degradation via its deacetylase activity. Knockdown of Snail abrogated the promoting effects of SIRT2 on migration and invasion of osteosarcoma cells. In conclusion, SIRT2 plays a crucial role in osteosarcoma metastasis by inhibiting Snail degradation and may serve as a novel therapeutic target to manage osteosarcoma.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Camundongos , Animais , Sirtuína 2/genética , Sirtuína 2/metabolismo , Neoplasias Ósseas/patologia , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Invasividade Neoplásica/genética , Movimento Celular , Linhagem Celular Tumoral , Osteossarcoma/patologia , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica
17.
Front Neurol ; 13: 930500, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388194

RESUMO

Background and purpose: Studies showed that patients with hemorrhagic stroke are at a higher risk of developing deep vein thrombosis (DVT) than those with ischemic stroke. We aimed to develop a risk score (intracerebral hemorrhage-associated deep vein thrombosis score, ICH-DVT) for predicting in-hospital DVT after ICH. Methods: The ICH-DVT was developed based on the Beijing Registration of Intracerebral Hemorrhage, in which eligible patients were randomly divided into derivation (60%) and internal validation cohorts (40%). External validation was performed using the iMCAS study (In-hospital Medical Complication after Acute Stroke). Independent predictors of in-hospital DVT after ICH were obtained using multivariable logistic regression, and ß-coefficients were used to generate a scoring system of the ICH-DVT. The area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration, respectively. Results: The overall in-hospital DVT after ICH was 6.3%, 6.0%, and 5.7% in the derivation (n = 1,309), internal validation (n = 655), and external validation (n = 314) cohorts, respectively. A 31-point ICH-DVT was developed from the set of independent predictors including age, hematoma volume, subarachnoid extension, pneumonia, gastrointestinal bleeding, and length of hospitalization. The ICH-DVT showed good discrimination (AUROC) in the derivation (0.81; 95%CI = 0.79-0.83), internal validation (0.83, 95%CI = 0.80-0.86), and external validation (0.88; 95%CI = 0.84-0.92) cohorts. The ICH-DVT was well calibrated (Hosmer-Lemeshow test) in the derivation (P = 0.53), internal validation (P = 0.38), and external validation (P = 0.06) cohorts. Conclusion: The ICH-DVT is a valid grading scale for predicting in-hospital DVT after ICH. Further studies on the effect of the ICH-DVT on clinical outcomes after ICH are warranted.

18.
Gut Microbes ; 14(1): 2143220, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36369946

RESUMO

Gut microbiota dysbiosis promotes metabolic syndromes (e.g., hypertension); however, the patterns that drive hypertensive pathology and could be targeted for therapeutic intervention are unclear. We hypothesized that gut microbes might translocate to the kidney to trigger hypertension. We aimed to uncover their method of colonization, and thereby how to maintain blood pressure homeostasis. Using combined approaches based on fluorescence in situ hybridization (FISH) and immunofluorescence staining, electron microscopy analysis, bacterial cultures, species identification, and RNA-sequencing-based meta-transcriptomics, we first demonstrated the presence of bacteria within the kidney of spontaneously hypertensive rats (SHRs) and its normotensive counterpart, Wistar-Kyoto rats (WKYs), and patients with hypertension. Translocated renal bacteria were coated with secretory IgA (sIgA) or remained dormant in the L-form. Klebsiella pneumoniae (K.pn) was identified in the kidneys of germ-free (GF) mice following intestinal transplantation, which suggested an influx of gut bacteria into the kidneys. Renal bacterial taxa and their function are associated with hypertension. Hypertensive hosts showed increased richness in the pathobionts of their kidneys, which were partly derived from the gastrointestinal tract. We also demonstrated the indispensable role of bacterial IgA proteases in the translocation of live microbes. Furthermore, Tartary buckwheat dietary intervention reduced blood pressure and modulated the core renal flora-host ecosystem to near-normal states. Taken together, the unique patterns of viable and dormant bacteria in the kidney provide insight into the pathogenesis of non-communicable chronic diseases and cardiometabolic diseases (e.g., hypertension), and may lead to potential novel microbiota-targeted dietary therapies.


Assuntos
Microbioma Gastrointestinal , Hipertensão , Microbiota , Ratos , Camundongos , Animais , Disbiose/microbiologia , Hibridização in Situ Fluorescente , Ratos Endogâmicos WKY , Hipertensão/etiologia , Microbiota/fisiologia , Rim/metabolismo , Bactérias/genética
19.
BMC Gastroenterol ; 22(1): 466, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397000

RESUMO

BACKGROUND: Given the limited effectiveness of the current Chinese colorectal cancer (CRC) screening procedure, adherence to colonoscopy remains low. We aim to develop and validate a scoring system based on individuals who were identified as having a high risk in initial CRC screening to achieve more efficient risk stratification and improve adherence to colonoscopy. METHODS: A total of 29,504 screening participants with positive High-Risk Factor Questionnaire (HRFQ) or faecal immunochemical test (FIT) who underwent colonoscopy in Tianjin from 2012-2020 were enrolled in this study. Binary regression analysis was used to evaluate the association between risk factors and advanced colorectal neoplasia. Internal validation was also used to assess the performance of the scoring system. RESULTS: Male sex, older age (age ≥ 50 years), high body mass index (BMI ≥ 28 kg/m2), current or past smoking and weekly alcohol intake were identified as risk factors for advanced colorectal neoplasm. The odds ratios (ORs) for significant variables were applied to construct the risk score ranging from 0-11: LR, low risk (score 0-3); MR, moderate risk (score 4-6); and HR, high risk (score 7-11). Compared with subjects with LR, those with MR and HR had ORs of 2.47 (95% confidence interval, 2.09-2.93) and 4.59 (95% confidence interval, 3.86-5.44), respectively. The scoring model showed an outstanding discriminatory capacity with a c-statistic of 0.64 (95% confidence interval, 0.63-0.65). CONCLUSIONS: Our results showed that the established scoring system could identify very high-risk populations with colorectal neoplasia. Combining this risk score with current Chinese screening methods may improve the effectiveness of CRC screening and adherence to colonoscopy.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Masculino , Pessoa de Meia-Idade , China/epidemiologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Detecção Precoce de Câncer/métodos , Fatores de Risco , Feminino
20.
Orthop Surg ; 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411502

RESUMO

OBJECTIVES: Bags such as handbags, shoulder bags, and backpacks are commonly used. However, it is difficult to assess the biomechanical effects of bag-carrying styles on the lumbar spine and paraspinal muscles using traditional methods. This study aimed to evaluate the biomechanical effects of bag-carrying styles on the lumbar spine. METHODS: We developed a hybrid model that combined a finite element (FE) model of the lumbar spine and musculoskeletal models of three bag-carrying styles. The image data was collected from a 26-years-old, 176 cm and 70 kg volunteer. OpenSim and ABAQUS were used to do the musculoskeletal analysis and finite analysis. Paraspinal muscle force, intervertebral compressive force (ICF), and intervertebral shear force (ISF) on L1 were calculated and loaded into the FE model to assess the stress distribution on the lumbar spine. RESULTS: Different paraspinal muscle activation occurred in the three bag-carrying models. The increase in the ICF generated by all three bags was greater than the bags' weights. The handbag produced greater muscle force, ICF, ISF, and peak stress on the nucleus pulposus than the backpack and shoulder bag of the same weight. Peak stress on the intervertebral discs in the backpack model and the L1-L4 segments of the shoulder bag model increased linearly with bag weight, and increased exponentially with bag weight in the handbag model. CONCLUSION: Unbalanced bag-carrying styles (shoulder bags and handbags) led to greater muscle force, which generated greater ICF, ISF, and peak stress on the lumbar spine. The backpack produced the least burden on the lumbar spine and paraspinal muscles. Heavy handbags should be used carefully in daily life.

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