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1.
ACS Appl Mater Interfaces ; 16(14): 17838-17845, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38556984

RESUMO

Changeable substituent groups of organic molecules can provide an opportunity to clarify the antibacterial mechanism of organic molecules by tuning the electron cloud density of their skeleton. However, understanding the antibacterial mechanism of organic molecules is challenging. Herein, we reported a molecular view strategy for clarifying the antibacterial switch mechanism by tuning electron cloud density of cinnamaldehyde molecule skeleton. The cinnamaldehyde and its derivatives were self-assembled into nanosheets with excellent water solubility, respectively. The experimental results show that α-bromocinnamaldehyde (BCA) nanosheets exhibits unprecedented antibacterial activity, but there is no antibacterial activity for α-methylcinnamaldehyde nanosheets. Therefore, the BCA nanosheets and α-methylcinnamaldehyde nanosheets achieve an antibacterial switch. Theoretical calculations further confirmed that the electron-withdrawing substituent of the bromine atom leads to a lower electron cloud density of the aldehyde group than that of the electron-donor substituent of the methyl group at the α-position of the cinnamaldehyde skeleton, which is a key point in elucidating the antimicrobial switch mechanism. The excellent biocompatibility of BCA nanosheets was confirmed by CCK-8. The mouse wound infection model, H&E staining, and the crawling ability of drosophila larvae show that as-prepared BCA nanosheets are safe and promising for wound healing. This study provides a new strategy for the synthesis of low-cost organic nanomaterials with good biocompatibility. It is expected to expand the application of natural organic small molecule materials in antimicrobial agents.


Assuntos
Acroleína/análogos & derivados , Nanoestruturas , Camundongos , Animais , Antibacterianos/farmacologia , Acroleína/farmacologia , Esqueleto
2.
J Nanobiotechnology ; 22(1): 12, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38166896

RESUMO

Ceria nanoparticles (CeO2NPs) exhibit great potential in cardiovascular disease and nonalcoholic fatty liver disease due to its excellent antioxidant capacity. However, the profitable effect of CeO2NPs on many diseases is almost all attributed to the regulation of ROS. Apart from the general antioxidant function, there seems to be no more distinct mechanism to reflect its unique multi-disease improvement effect. Here, we for the first time reveal a new discovery of CeO2NPs in mimicking nitric oxide synthase (NOS) by catalyzing L-arginine (L-Arg) to produce nitric oxide (NO) or the derivatives. NOS-like activity of CeO2NPs is original and associated with multiple factors like substrate concentration, pH, temperature and time, etc. where oxygen vacancy ratio plays a more critical role. Meanwhile, NOS-like activity of CeO2NPs successfully elevates NO secretion in endothelial cells and macrophages without expanding eNOS/iNOS expression. Importantly, NOS-like activity of CeO2NPs and the responsive endogenous NO promote the re-distribution of blood lipids and stabilize eNOS expression but suppress iNOS, thus collectively alleviate the accumulation of vascular plaque. Altogether, we provide a new angle of view to survey the outstanding potential of CeO2NPs, apart from the inevitable antioxidant capacity, the covert but possible and more critical NOS-like enzymatic activity is more noteworthy.


Assuntos
Antioxidantes , Células Endoteliais , Nanopartículas , Óxido Nítrico Sintase , Placa Aterosclerótica , Antioxidantes/metabolismo , Arginina/metabolismo , Células Endoteliais/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Nanopartículas/química
3.
BMJ Open ; 13(12): e076418, 2023 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-38151272

RESUMO

INTRODUCTION: High myopia is a pressing public health concern due to its increasing prevalence, younger trend and the high risk of blindness, particularly in East Asian countries, including China. The China Alliance of Research in High Myopia (CHARM) is a newly established consortium that includes more than 100 hospitals and institutions participating across the nation, aiming to promote collaboration and data sharing in the field of high myopia screening, classification, diagnosis and therapeutic development. METHODS AND ANALYSIS: The CHARM project is an ongoing study, and its initiation is distinguished by its unprecedented scale, encompassing plans to involve over 100 000 Chinese patients. This initiative stands out not only for its extensive scope but also for its innovative application of artificial intelligence (AI) to assist in diagnosis and treatment decisions. The CHARM project has been carried out using a 'three-step' strategy. The first step involves the collection of basic information, refraction, axial length and fundus photographs from participants with high myopia. In the second step, we will collect multimodal imaging data to expand the scope of clinical information, for example, optical coherence tomography and ultra-widefield fundus images. In the final step, genetic testing will be conducted by incorporating patient family histories and blood samples. The majority of data collected by CHARM is in the form of images that will be used to detect and predict the progression of high myopia through the identification and quantification of biomarkers such as fundus tessellation, optic nerve head and vascular parameters. ETHICS AND DISSEMINATION: The study has received approval from the Ethics Committee of Beijing Tongren Hospital (TREC2022-KY045). The establishment of CHARM represents an opportunity to create a collaborative platform for myopia experts and facilitate the dissemination of research findings to the global community through peer-reviewed publications and conference presentations. These insights can inform clinical decision-making and contribute to the development of new treatment modalities that may benefit patients worldwide. TRIAL REGISTRATION NUMBER: ChiCTR2300071219.


Assuntos
Inteligência Artificial , Miopia , Humanos , Bancos de Espécimes Biológicos , Miopia/diagnóstico , Miopia/terapia , Miopia/epidemiologia , Refração Ocular , Cegueira
4.
RSC Adv ; 13(49): 34724-34732, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38035235

RESUMO

Searching for electrode materials with good electrical conductivity, fast charge/discharge rates and high storage capacity is essential for the development of high-performance metal ion batteries. Here, by performing first principles calculations, we have explored the feasibility of using two dimensional (2D) covalent organic frameworks (COFs) constructed by tri-quinazoline, triquinoxalinylene and benzoquinone, and tribenzoquinoxaline-5,10-dione and benzoquinone (BQ2), as electrode materials for lithium and sodium ion batteries. All the designed 2D COFs show good structure stability and are semiconductors with a band gap of 1.63-2.93 eV because of the high electron conjugation of the skeletons. The pyrazine N and carbonyl groups are revealed to be the active sites to combine Li/Na, while the Li-/Na-binding strength can be highly enhanced when the pyrazine N and the carbonyl group are located in adjacent sites. The designed 2D COFs show a low Li and Na diffusion barrier in the range of 0.28-0.56 eV to guarantee high rate performance for LIBs/SIBs. With abundant redox active sites, 2D BQ2-COF shows a high theoretical capacity of 1030 mA h g-1 with an average open circuit voltage of 0.80 and 0.67 V for LIBs and SIBs, respectively, which is comparable to that of the most advanced inorganic anode materials. Composed of only light elements, the designed 2D COFs are predicted to be promising anode materials with high energy density, good conductivity and high-rate performance for sustainable LIBs and SIBs.

5.
Vascular ; : 17085381231154354, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37526208

RESUMO

OBJECTIVES: To evaluate the efficacy and clinical outcomes of accurate embolization of endoleaks after fenestrated thoracic endovascular aortic repair (F-TEVAR) for thoracic aortic dissections. METHODS: Twenty patients with endoleaks (17 type I and 3 type II) after fenestrated thoracic endovascular aortic repair (F-TEVAR) were embolized using detachable and ordinary coils. We assessed the success rate and complications of the operation, and its effects, through clinical and CT follow-up. RESULTS: The mean clinical follow-up duration was 25.68 ± 11.07 months (3-44 months). During follow-up, all endoleaks were completely embolized and aortic remodeling was improved. Secondary endoleaks occurred in four patients who were embolized twice. No other complications or death were reported. CONCLUSION: Embolization using detachable and ordinary coils is effective and safe for the treatment of endoleaks after fenestrated thoracic endovascular aortic repair.

6.
Elife ; 122023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37561022

RESUMO

Postmenopausal atherosclerosis (AS) has been attributed to estrogen deficiency. However, the beneficial effect of hormone replacement therapy (HRT) is lost in late postmenopausal women with atherogenesis. We asked whether aging-related iron accumulation affects estrogen receptor α (ERα) expression, thus explaining HRT inefficacy. A negative correlation has been observed between aging-related systemic iron deposition and ERα expression in postmenopausal AS patients. In an ovariectomized Apoe-/- mouse model, estradiol treatment had contrasting effects on ERα expression in early versus late postmenopausal mice. ERα expression was inhibited by iron treatment in cell culture and iron-overloaded mice. Combined treatment with estradiol and iron further decreased ERα expression, and the latter effect was mediated by iron-regulated E3 ligase Mdm2. In line with these observations, cellular cholesterol efflux was reduced, and endothelial homeostasis was disrupted. Consequently, AS was aggravated. Accordingly, systemic iron chelation attenuated estradiol-triggered progressive AS in late postmenopausal mice. Thus, iron and estradiol together downregulate ERα through Mdm2-mediated proteolysis, providing a potential explanation for failures of HRT in late postmenopausal subjects with aging-related iron accumulation. This study suggests that immediate HRT after menopause, along with appropriate iron chelation, might provide benefits from AS.


Assuntos
Aterosclerose , Receptor alfa de Estrogênio , Humanos , Feminino , Camundongos , Animais , Receptor alfa de Estrogênio/genética , Pós-Menopausa , Terapia de Reposição de Estrogênios , Aterosclerose/metabolismo , Estradiol , Terapia de Reposição Hormonal , Quelantes de Ferro
7.
Comput Methods Programs Biomed ; 240: 107605, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37390795

RESUMO

PURPOSE: A capsule robot can be controlled inside gastrointestinal (GI) tract by an external permanent magnet outside of human body for finishing non-invasive diagnosis and treatment. Locomotion control of capsule robot relies on the precise angle feedback that can be achieved by ultrasound imaging. However, ultrasound-based angle estimation of capsule robot is interfered by gastric wall tissue and the mixture of air, water, and digestive matter existing in the stomach. METHODS: To tackle these issues, we introduce a heatmap guided two-stage network to detect the position and estimate the angle of the capsule robot in ultrasound images. Specifically, this network proposes the probability distribution module and skeleton extraction-based angle calculation to obtain accurate capsule robot position and angle estimation. RESULTS: Extensive experiments were finished on the ultrasound image dataset of capsule robot within porcine stomach. Empirical results showed that our method obtained small position center error of 0.48 mm and high angle estimation accuracy of 96.32%. CONCLUSION: Our method can provide precise angle feedback for locomotion control of capsule robot.


Assuntos
Robótica , Animais , Suínos , Humanos , Robótica/métodos , Ultrassonografia
8.
Acta Biomater ; 157: 175-186, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36503078

RESUMO

Accumulating reports indicate that adipose-derived stem cell (ADSC)-originating exosomes (ADSC-Exos) provide a potential strategy for diabetic wound repair. However, the disadvantages of exosomes, such as fast decrease of biological activity and unknown biological mechanisms, limit their clinical application. Herein, hypoxia-pretreated ADSC-Exo (ADSC-HExo)-embedded GelMA hydrogels (GelMA-HExo) were developed via non-covalent force and physical embedding. These materials rapidly converted into a gel state under illumination, thereby adapting to irregular diabetic wounds. The regulatory mechanism of circ-Snhg11 delivery by exosomes in accelerating diabetic wound healing was explored. In vitro, GelMA-HExo hydrogels had a loose porous structure, and a stable degradation and expansion rate. In vivo, GelMA-HExo hydrogels promoted wound healing in diabetic mice. In particular, ADSC-HExos had a good therapeutic effect, in which circ-Snhg11 expression was increased. Furthermore, circ-Snhg11-modified ADSC-Exos increased the migratory, proliferative and blood vessel regeneration potential of vascular endothelial cells (ECs). In addition, overexpression (OE) of NFE2L2-HIF1α or inhibition of miR-144-3p-both of which are members of the miR-144-3p/NFE2L2/HIF1α pathway downstream of circ-Snhg11-reversed the therapeutic effects of circ-Snhg11. In summary, this study explored the effects and downstream targets of hypoxic engineered exosome hydrogels in managing diabetic wound repair. These hydrogels are expected to serve as a new approach for clinical treatment and to have application possibilities in other disease areas. STATEMENT OF SIGNIFICANCE: ADSC-Exo treatment can accelerate diabetic wound healing via circRNA delivery. But how to reverse the problems such as poor mechanical properties, low biological activity, short duration of effect and high risk of sudden release of exosomes needs investigation. We constructed exosome-embedded GelMA (GelMA-Exo) hydrogels and found that GelMA-Exo treatment could significantly promote diabetic wound healing. Further study found that exosomes from hypoxia-pretreated ADSCs (ADSC-HExos) had an enhanced therapeutic effect than normal exosomes. The regulation mechanism study found that circ-Snhg11 delivery from GelMA-HExo incremented survival and maintained endothelial cell (EC) function, possibly via the activation of miR-144-3p/NFE2L2/HIF1α signaling. These findings suggest a new therapeutic strategy for patients with diabetic ulcer.


Assuntos
Diabetes Mellitus Experimental , Exossomos , MicroRNAs , Camundongos , Animais , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Diabetes Mellitus Experimental/metabolismo , Exossomos/metabolismo , Células Endoteliais , Cicatrização , MicroRNAs/farmacologia
9.
Adv Exp Med Biol ; 1370: 103-111, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36324043

RESUMO

Knowing the seasonality of COVID-19 helps decision-makers to take suitable interventions against the pandemic. In this study, we performed the Brown-Forsythe variance analysis on seasonal variations on different indicators based on the data on COVID-19 for the United States provided publicly by WHO. Our study finds that the seasonality of weekly cases and deaths of COVID-19 are strongly statistically supported by the data. The weekly total cases(/deaths) in winter are three to seven times(/two to three times) more than the other three single seasons. The ICU patients in winter and autumn are four to five times more than spring. The weekly hospital admissions in winter are four times more than spring. The mean of the positive rate in winter is five times more than spring. The findings of this research can be a reference in decision-making when taking interventions against the pandemic, such as taking stricter interventions in winter while considering less strict interventions in summer, etc.


Assuntos
COVID-19 , Humanos , Estados Unidos/epidemiologia , Estações do Ano , COVID-19/epidemiologia , Hospitalização , Biometria
10.
J Ethnopharmacol ; 292: 115206, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35301099

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Oridonin (Ori), extracted from Isodon rubescens (Hemsl.) H.Hara, is a well-known traditional Chinese herbal medicinal product that possesses antioxidant and anti-inflammatory activities. Oxidative stress and inflammation are the main pathophysiological mechanisms in hindlimb IR injury. However, whether Ori has a protective effect on hind limb IR injury is unknown. AIM OF THE STUDY: The present study was designed to determine the effect of Ori on hindlimb IR injury and its relationship with oxidative stress and inflammation. MATERIALS AND METHODS: The hind limb IR injury model in mice was used to evaluate the protective effect and related mechanisms of Ori. Forty-eight C57BL/6 mice (n = 12 per group) were randomly divided into four groups: Sham group; IR group; IR + Ori (10 mg/kg) group and IR + Ori (20 mg/kg) group. Mice in the IR and IR + Ori groups were subjected to hindlimb IR injury, while mice in the Sham group were subjected to no hindlimb IR injury. HE staining, Masson's staining, TTC staining, DHE staining, TUNEL staining, western blotting analysis and quantitative real-time PCR were employed to explore the mechanisms by which Ori exerts a protective effect on a classical hindlimb IR model in mice. RESULTS: We found that Ori pretreatment prevented muscle damage and decreased cell apoptosis levels compared with the vehicle control. Moreover, the SOD2, CAT, MDA and ROS levels in muscle showed that Ori could significantly reduce oxidative stress in hindlimb IR mice, while the IL-1ß and TNF-α levels in muscle showed that Ori could significantly attenuate IR-induced inflammation. We also found that Ori could increase the expression of Nrf2 and its downstream protein HO-1 and inhibit the expression levels of NLRP3-related proteins (NLRP3, ASC and Caspase-1) in vivo. CONCLUSIONS: Our study suggested that Ori has a protective effect on hindlimb IR injury, which may be related to Nrf2-mediated oxidative stress and NLRP3-mediated inflammasome activation.


Assuntos
Fator 2 Relacionado a NF-E2 , Traumatismo por Reperfusão , Animais , Diterpenos do Tipo Caurano , Membro Posterior , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo , Traumatismo por Reperfusão/metabolismo
11.
Comput Methods Biomech Biomed Engin ; 25(11): 1211-1221, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34843417

RESUMO

The aim of this study is to perform patient-specific hemodynamic simulations of patients with iliac vein compression syndrome (IVCS) and evaluate the deep venous thrombosis (DVT) potential, with clinical observations as reference. 15 patient-specific IVCS models were reconstructed from computed tomography venography (CTV) data, and divided into three groups, i.e. two groups with thrombosis: Group A (complete obstruction) and Group B (incomplete obstruction), and a third group without DVT, Group C. Hemodynamic simulations were conducted with patient-specific inlet flow rates. The blood residue was predicted using the blood stasis model. Time histories of old blood volume fraction (OBVF) was obtained, in addition to conventional hemodynamic parameters such as wall shear stress (WSS). The mean area-averaged WSS of the stenosis region for Group A and Group B were 3.68 Pa and 1.78 Pa, respectively. For the telecentric end region, the WSS were 0.76 Pa and 0.58 Pa, respectively. For Group C, the WSS at these two regions were 4.61 Pa and 1.57 Pa, respectively. The OBVF was 74.0% at the stenosis region and 76.2% at the telecentric end region for Group A, much higher than 4.8% and 43.1% of Group B. For Group C, the OBVF at the two regions were close to 0. This corresponded well with clinical observations. The potential of DVT can be predicted through patient-specific hemodynamic simulations in combination of blood stasis model. The findings of this study are of great significance for the preoperative evaluation and treatment prognosis of IVCS patients with DVT.


Assuntos
Síndrome de May-Thurner , Trombose Venosa , Constrição Patológica/terapia , Hemodinâmica , Humanos , Veia Ilíaca/diagnóstico por imagem , Síndrome de May-Thurner/terapia , Estudos Retrospectivos , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/terapia
12.
Clin Appl Thromb Hemost ; 27: 10760296211051708, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34846211

RESUMO

Carotid and vertebral artery dissections are estimated to account for ∼20% of strokes in patients under 45-years-old. This meta-analysis compared the efficacy and safety of treatment with anticoagulants versus antiplatelet agents to determine the optimal therapy. We searched 4 electronic databases for clinical trials published from January 1, 1980 to August 25, 2021 that included patients who received anticoagulant or antiplatelet therapy for carotid and/or vertebral artery dissections. The curative effect was judged by recanalization evaluated by imaging. The primary outcomes were all cause death and ischemic stroke; secondary outcomes included hemorrhage and transient ischemic attack (TIA). Patients who received only a single drug treatment were divided into antiplatelet or anticoagulant groups; all received conservative treatment without surgical intervention. For this investigation, we pooled the available studies to conduct a meta-analysis, which included 7 articles with 1126 patients. The curative effect of vascular recanalization was not significantly different between the 2 treatment groups (odds ratio [OR] = 0.913, 95% confidence interval [CI]: 0.611-1.365, P = .657); similarly, no significant differences were found regarding the primary outcomes all cause death (OR = 1.747, 95%CI: 0.202-15.079, P = .612) and ischemic stroke (OR = 2.289, 95%CI: 0.997-5.254, P = .051). Patients treated with anticoagulants were more likely to experience TIA (OR = 0.517, 95%CI: 0.252-1.060, P = .072) and hemorrhage (OR = 0.468, 95%CI: 0.210-1.042, P = .063), but the differences were not statistically significant. Overall, there were no statistically significant differences between anticoagulant therapy and antiplatelet therapy for the treatment of carotid and vertebral artery dissections.


Assuntos
Anticoagulantes/administração & dosagem , Ensaios Clínicos como Assunto , Inibidores da Agregação Plaquetária/administração & dosagem , Dissecação da Artéria Vertebral/tratamento farmacológico , Humanos
13.
Front Neurosci ; 15: 715222, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675764

RESUMO

Iron regulatory protein 2 (IRP2) deficiency in mice and humans causes microcytic anemia and neurodegeneration due to functional cellular iron depletion. Our previous in vitro data have demonstrated that Irp2 depletion upregulates hypoxia-inducible factor subunits Hif1α and Hif2α expression; inhibition of Hif2α rescues Irp2 ablation-induced mitochondrial dysfunction; and inhibition of Hif1α suppresses the overdose production of lactic acid derived from actively aerobic glycolysis. We wonder whether Hif1α and Hif2α are also elevated in vivo and play a similar role in neurological disorder of Irp2 -/- mice. In this study, we confirmed the upregulation of Hif2α, not Hif1α, in tissues, particularly in the central nervous system including the mainly affected cerebellum and spinal cord of Irp2 -/- mice. Consistent with this observation, inhibition of Hif2α by PT-2385, not Hif1α by PX-478, prevented neurodegenerative symptoms, which were proved by Purkinje cell arrangement from the shrunken and irregular to the full and regular array. PT-2385 treatment did not only modulate mitochondrial morphology and quality in vivo but also suppressed glycolysis. Consequently, the shift of energy metabolism from glycolysis to oxidative phosphorylation (OXPHOS) was reversed. Our results indicate that Irp2 depletion-induced Hif2α is, in vivo, in charge of the switch between OXPHOS and glycolysis, suggesting that, for the first time to our knowledge, Hif2α is a clinically potential target in the treatment of IRP2 deficiency-induced neurodegenerative syndrome.

14.
J Diabetes Complications ; 35(11): 108020, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34507876

RESUMO

Previous studies found that hypoxic pretreatment of endothelial progenitor cells (EPCs) prior to transplantation had a greater therapeutic effect than untreated EPCs in promoting diabetic wound healing. However, the exact mechanism is uncertain. Here, circRNA expression in EPCs after hypoxic treatment was investigated. High-throughput sequencing was used to assess abnormal expression by EPCs of circular RNAs (circRNAs) following hypoxic pretreatment. Additionally, an in vivo full-thickness skin defect mouse model was used to assess the effects of transplanted EPCs on diabetic wound closure. Subsequently, the regulatory mechanism and targets were studied. The results showed that circ-Klhl8 overexpression suppressed hyper glucose-induced endothelial cell damage by activating autophagy. MiR-212-3p and SIRT5 were identified as the downstream targets of circ-Klhl8. Circ-Klhl8 overexpression promoted skin wound healing by regulating SIRT5-mediated autophagy. In conclusion, the study found that circ-Klhl8 overexpression increased the EPC therapeutic effect in promoting diabetic wound healing by targeting the miR-212-3p/SIRT5 axis.


Assuntos
Diabetes Mellitus , Células Progenitoras Endoteliais , MicroRNAs , RNA Circular/genética , Sirtuínas , Cicatrização , Animais , Camundongos , MicroRNAs/genética , Transplante de Células-Tronco , Cicatrização/genética
15.
Transl Cancer Res ; 10(2): 694-713, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35116402

RESUMO

BACKGROUND: The genes and genetic mechanisms underlying the occurrence and progression of papillary thyroid carcinoma (PTC) are still unknown. This study aimed to find candidate genes related to the pathogenesis and progression of PTC. METHODS: RNA sequencing (RNA-seq) data of PTC and normal tissues were downloaded from The Cancer Genome Atlas (TCGA) database with clinical stage data to form a test, validation, and clinical-stage data matrix. We used the test data set to analyze differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) to find those gene clusters highly correlated with PTC. We then verified the expression of genes in the interested modules using the validation matrix. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the reliability of the expression of selected genes. Five key genes (GDF15, LCN2, KCNN4, SH3BGRL3, and MMP2) were used to analyze the connection between gene expression and the American Joint Committee on Cancer (AJCC) stage. The upregulated and downregulated DEGs, along with the modules of interest, were subjected to Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). RESULTS: We used WGCNA to find two modules of interest, the yellow module, which was positively associated with PTC, and the blue module, which was negatively correlated with PTC. Four genes (GDF15, LCN2, KCNN4, and SH3BGRL3) from the yellow module were determined to be highly expressed in PTC in the test data matrix and were verified in both the validation data matrix and quantitative real-time PCR, which indicated that these four genes were highly correlated with the occurrence of the PTC. Furthermore, these four genes also had a significantly higher expression in the advanced levels of pathological T, N, and AJCC stage, meaning that they were correlated with the progression of PTC. Genes in the yellow module and upregulated DEGs were significantly enriched in three vital signaling pathways, including focal adhesion, extracellular matrix (ECM)-receptor interaction, and the PI3K-Akt signaling pathway. CONCLUSIONS: Four candidate genes (GDF15, LCN2, KCNN4, and SH3BGRL3) may be potential biomarkers for the PTC's pathogenesis and may be useful for predicting the disease stage.

16.
Cell Biosci ; 10(1): 137, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33292517

RESUMO

BACKGROUND: Macrophages that accumulate in atherosclerotic plaques contribute to progression of the lesions to more advanced and complex plaques. Although iron deposition was found in human atherosclerotic plaques, clinical and pre-clinical studies showed controversial results. Several epidemiological studies did not show the positive correlation between a systemic iron status and an incidence of cardiovascular diseases, suggesting that the iron involvement occurs locally, rather than systemically. RESULTS: To determine the direct in vivo effect of iron accumulation in macrophages on the progression of atherosclerosis, we generated Apoe-/- mice with a macrophage-specific ferroportin (Fpn1) deficiency (Apoe-/-Fpn1LysM/LysM). Fpn1 deficiency in macrophages dramatically accelerated the progression of atherosclerosis in mice. Pathophysiological evidence showed elevated levels of reactive oxygen species, aggravated systemic inflammation, and altered plaque-lipid composition. Moreover, Fpn1 deficiency in macrophages significantly inhibited the expression of ABC transporters (ABCA1 and ABCG1) by decreasing the expression of the transcription factor LXRα, which reduced cholesterol efflux and therefore promoted foam cell formation and enhanced plaque formation. Iron chelation relieved the symptoms moderately in vivo, but drastically ex vivo. CONCLUSIONS: Macrophage iron content in plaques is a critical factor in progression of atherosclerosis. The interaction of iron and lipid metabolism takes place in macrophage-rich atherosclerotic plaques. And we also suggest that altering intracellular iron levels in macrophages by systemic iron chelation or dietary iron restriction may be a potential supplementary strategy to limit or even regress the progression of atherosclerosis.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32974316

RESUMO

OBJECTIVE: Precise hip cup positioning is essential for the prevention of component impingement and dislocation in robotic assisted total hip arthroplasty (THA). Currently, the robotic system uses a mechanical alignment guide (MAG) for cup placement, which is one-size-fits-all, and the optimal cup positioning is controversial. Robotic assisted THA has not used any personalized cup positioning guides. The goal of this study was to identify an optimal guide for cup placement in robotic assisted THA to improve prognosis and life quality after THA. MATERIALS AND METHODS: Pelvis and femoral CT data of 47 participants were retrospectively collected for preoperative planning of robotic THA. The universal MAG guide and three personalized guides, including acetabular rim labrum guide (ARLG), transverse acetabular ligament guide (TALG), and ischiatic-pubis line guide (IPLG), were used to pose cups in the acetabulum of each participant. The position of cups was evaluated by inclination and anteversion; the function of hip joints was evaluated by hip ranges of motion, including abduction, adduction, extension, flexion, internal rotation, and external rotation. RESULTS: In terms of cup positioning, ARLG provided a bigger cup inclination (p < 0.0001), while IPLG and TALG provided smaller cup inclination (p < 0.001) than MAG; the three personalized guides provided larger cup anteversion (p < 0.0001) than MAG. In terms of HROMs, compared with the use of MAG, the use of three personalized guides significantly decreased abduction (p < 0.0001), extension (p < 0.0001), and external rotation (p < 0.0001), but increased significantly flexion (p < 0.0001) and internal rotation (p < 0.0001); the use of ARLG significantly reduced adduction (p < 0.0001), but the use of IPLG and TALG increased adduction (p < 0.0001). CONCLUSION: Compared with MAG, personalized guides provided greater flexion and internal rotation, which may reduce the risk of posterior dislocation. Among the three personalized guides, IPLG is the most reliable one for the preoperative planning of robotic assisted THA.

18.
Materials (Basel) ; 11(10)2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30347665

RESUMO

Polyester fibers are used in various fields, due to their excellent mechanical and chemical stability. However, the lack of conductivity limits their application potential. In order to prepare conductive polyester fibers, silver is one of the most widely used materials to coat the surface of the fibers. This work aimed to prepare silver-coated polyester fibers by a continuous two-step method, which combined the operations of continuous electroless plating and electroplating. Meanwhile, we designed specialized equipment for the continuous plating of silver on the polyester fibers under a dynamic condition. The mechanical property, washability, electrical resistivity, and electrical conductivity of the resultant conductive polyester fibers obtained from different silver-plating conditions were also characterized. The results demonstrated that the conductive fibers prepared by continuous two-step silver plating equipment, had good electrical conductivity with better mechanical properties and washability.

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