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1.
Arch Biochem Biophys ; : 110063, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880321

RESUMO

To investigate the potential molecular mechanism of miR-34a in Sjögren's syndrome (SS). Transmission electron microscopy was used to observe the salivary gland tissues of mild and severe SS patients. SS mouse model was constructed and injected with miR-34a antagonist. HSGE cells were transfected with miR-34a mimic. Starbase predicted miR-34a binding sites and validated them with dual-luciferase reporter assays. Immunohistochemistry, HE staining, CCK-8, TUNEL assay, flow cytometry, immunofluorescence and Western Blot were used to investigate the effects of miR-34a on NF-κB signaling and mitochondrial pathway of apoptosis in HSGE cells. Severe SS patients showed obvious mitochondrial damage and apoptosis in salivary glands. MiR-34a was overexpressed and NF-κB signaling is activated in salivary glands of severe SS patients. Inhibition of miR-34a alleviated salivary gland injury in SS mice, as well as inhibited the activation of NF-κB signaling and mitochondrial pathway of apoptosis. In conclusion, miR-34a promoted NF-κB signaling by targeting IκBα, thereby causing mitochondrial pathway apoptosis and aggravating SS-induced salivary gland damage.

2.
J Transl Med ; 22(1): 96, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263194

RESUMO

BACKGROUND: Periodontitis is a chronic oral inflammatory disease that seriously affects people's quality of life. The purpose of our study was to investigate the correlation between the systemic immune inflammation index (SII) and periodontitis by utilizing a large national survey. This will establish a reference for the early identification and management of periodontitis. METHODS: This study comprised the adult US population who participated in a national periodontitis surveillance project during the six years from 2009 to 2014. Through the utilization of univariate and multivariate weighted logistic regression, we investigated the correlation between the systemic immune inflammation index and periodontitis. Additionally, we employed sensitivity analyses to evaluate the robustness of our findings. RESULTS: The study involved 10,366 participants with an average age of 51.00 years, of whom 49.45% were male (N = 5126) and 50.55% were female (N = 5240). The prevalence of periodontitis is estimated to be about 38.43% in the US adults aged 30 or older population. Our logistic regression models indicated a positive association between a SII higher than 978 × 109/L and periodontitis. The elder group (aged 50 or older) with SII higher than 978 × 109/L demonstrated a significant correlation with periodontitis in the fully adjusted model (Odds Ratio [OR] = 1.409, 95% Confidence Interval [CI] 1.037, 1.915, P = 0.022). However, there is no statistical difference among adults aged 30 to 50. The robustness of our findings was confirmed through sensitivity analyses. CONCLUSIONS: Our study highlights that SII is associated with periodontitis in a nationally representative sample of US adults. And the SII is significantly associated with a high risk of periodontitis in individuals aged 50 or older.


Assuntos
Periodontite , Qualidade de Vida , Adulto , Feminino , Masculino , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Inflamação , Modelos Logísticos
3.
Front Pharmacol ; 14: 1294297, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38089045

RESUMO

Background: Recent reports have suggested that antihypertensive drugs may play an oncogenic role in common cancers, but it is still uncertain whether this could influence the risk of oral cancer. Through two-sample Mendelian randomization (MR), we sought to assess the causal effect of antihypertensive drugs on oral cancer outcomes. Methods: To proxy the exposure of antihypertensive drugs, we utilized two genetic instruments, including expression quantitative trait loci of drug target genes and genetic variants within or around drug target genes related to blood pressure from genome-wide association studies. Inverse-variance-weighted MR (IVW-MR) and summary-data-based MR (SMR) were employed to compute the instrument effect estimates. Results: It was observed through IVW-MR analysis that there is a positive relationship between KCNH2 (target of beta-adrenoceptor blockers)-mediated blood pressure and oral cancer (odds ratio [OR] = 1.197, 95% confidence interval [CI] = 1.028-1.394). Similarly, SMR analysis demonstrated that a higher expression of KCNH2 (target of beta-adrenoceptor blockers) was linked to a greater risk of oral cancer (OR = 2.223, 95% CI = 1.094-4.516). Both analyses yielded no consistent evidence of other associations. Conclusion: This two-sample MR study proposed a latent causal association between KCNH2 (target of beta-adrenoceptor blockers) inhibition and diminished risk of oral cancer.

4.
Front Oncol ; 13: 1326023, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38156109

RESUMO

Triple-negative breast cancer (TNBC) is the most refractory subtype of breast cancer, and effective treatments are urgently needed owing to its poor prognosis. Surgery, radiotherapy, and chemotherapy, alone or in combination, are the leading choices for TNBC therapy. Although promising approaches and procedures have emerged, several challenges, such as off-target effects, drug resistance, and severe side effects, remain to be addressed. Recently, transient receptor potential channel mucolipin 1 (TRPML1) has attracted the attention of researchers because its expression has been implicated in numerous diseases, including cancer. TRPML1 regulates biological events and signaling pathways, including autophagic flux, exocytosis, ionic homeostasis, and lysosomal biogenesis, all contributing to tumorigenesis and cancer progression. TRPML1 also functions as a building block for cancer cell growth, mitogenic signaling, priming tissues for metastasis, and activation of transcriptional programs, processes involved in several malignant tumors. This review provides an overview of breast cancer epidemiology and diagnostic techniques and then discusses the existing therapeutics. Additionally, we elaborate on the development of, and associated challenges to, TNBC diagnostics and treatment and the feasibility of TRPML1 as a therapeutic target for TNBC.

5.
Mol Cell Biochem ; 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37973706

RESUMO

Natural Killer (NK) cell is the first batch of re-constructed cell populations after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and its delayed reconstitution inevitably causes poor outcome. The traditional Chinese medicine Huiyang-Guben decoction (HYGB) has been clinically used in patients undergoing allo-HSCT, but its effect on NK cell reconstruction is still unclear. 40 patients with allo-HSCT therapy were randomly divided into the control group and the HYGB group, and were given oral administration of normal saline or HYGB for 4 weeks before allo-HSCT, respectively. NK cells were cultured and treated with transforming growth factor ß (TGF-ß) and HYGB in vitro, and cell viability, cell apoptosis, and the function of NK cells were evaluated. Functional verification experiments were performed by knocking down signal transduction molecule 7 (Smad7) in NK cells before TGF-ß and HYGB treatment. Clinical data suggested that HYGB intervention decreased the incidence of acute graft-versus-host disease after allo-HSCT, and increased the proportion of NK cell population. Meanwhile, HYGB improved cell viability, restrained apoptotic cell death, and enhanced cell killing activity of NK cells in patients with allo-HSCT. Notably, we found that HYGB significantly increased the expression level of Smad7 and the phosphorylation level of signal transducer and activator of transcription 3 (Stat3) in NK cells from patients with allo-HSCT. Moreover, HYGB alleviated TGF-ß-induced NK cell impairment and re-activated the Smad7/Stat3 signaling in vitro, while silencing Smad7 reversed the protective effect of HYGB on TGF-ß-treated NK cells. HYGB promotes NK cell reconstruction and improves NK cell function after allo-HSCT through activating the Smad7/Stat3 signaling pathway.

6.
Proc Natl Acad Sci U S A ; 120(39): e2302500120, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37722050

RESUMO

To mount appropriate responses, T cells integrate complex sequences of receptor stimuli perceived during transient interactions with antigen-presenting cells. Although it has been hypothesized that the dynamics of these interactions influence the outcome of T cell activation, methodological limitations have hindered its formal demonstration. Here, we have engineered the Light-inducible T cell engager (LiTE) system, a recombinant optogenetics-based molecular tool targeting the T cell receptor (TCR). The LiTE system constitutes a reversible molecular switch displaying exquisite reactivity. As proof of concept, we dissect how specific temporal patterns of TCR stimulation shape T cell activation. We established that CD4+ T cells respond to intermittent TCR stimulation more efficiently than their CD8+ T cells counterparts and provide evidence that distinct sequences of TCR stimulation encode different cytokine programs. Finally, we show that the LiTE system could be exploited to create light-activated bispecific T cell engagers and manipulate tumor cell killing. Overall, the LiTE system provides opportunities to understand how T cells integrate TCR stimulations and to trigger T cell cytotoxicity with high spatiotemporal control.


Assuntos
Células Apresentadoras de Antígenos , Linfócitos T CD8-Positivos , Citocinas , Células Epiteliais , Ativação Linfocitária
7.
Nanoscale Adv ; 5(15): 3934-3941, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37496618

RESUMO

Ag cluster catalyst-based oxidation of CO to CO2 is an important way to remove CO at low temperatures. However, the instability of silver clusters seriously limits the catalytic application. Herein, sub-nanosized EMT zeolite nanoparticles served as Ag cluster carriers with high selectivity, low coordination, and unsaturated atom active sites. The silver clusters with sub-nanometer size can be controlled with different charge states and loading rates. A detection film with 500 nm was further prepared by assembling the Ag-EMT composites with a small amount of Nalco as an adhesive. For CO detection, a completely enclosed gas sensing device based on in situ infrared spectroscopy was employed without air interference. CO was accurately introduced into the detection chamber and catalysed into CO2 by silver loaded EMT zeolite films, and the whole process was accurately recorded by infrared spectroscopy. CO with a detection range of 2-50 ppm was realized, showing great application potential in gas monitoring.

8.
Genet Mol Biol ; 46(2): e20220277, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37272834

RESUMO

Long non-coding RNA AK001796 was initially identified altered in lung cancer. Recent research showed it could participate in the prognosis of hepatocellular carcinoma (HCC). However, the general biological role of AK001796 and its underlying mechanisms in HCC remain unclear. Here we demonstrated that the expression level of AK001796 in HCC tissues and cell lines was up-regulated. Silencing AK001796 suppressed the proliferation ability of HCC cells. Through dual luciferase reporter assays and loss/gain of functions studies, we identified that AK001796 could bind to miR-150, a star microRNA, promoting HCC proliferation. Furthermore, it was reported that growth factor receptor binding protein 2-associated binder 1 (GAB1) is a target gene of miR-150. Owing to AK001796 being a decoy for miR-150 and binding the same putative sites of miR-150 as GAB1, we presented that inhibition of miR-150 in AK001796 silencing cells reversed the reduction in GAB1. Subsequently, our findings demonstrated that silencing AK001796 can impair phospho-ERK1/2 and phospho-AKT. In conclusion, our investigation revealed that AK001796 promoted proliferation by enhancing phospho-ERK1/2 and phospho-AKT through AK001796/miR-150/GAB1 axis in HCC. These results provided further evidence for the critical roles of AK001796 accumulating HCC and suggested that AK001796 might act as an HCC biomarker in clinical treatment.

9.
Nutr Res Pract ; 17(3): 387-396, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37266115

RESUMO

BACKGROUND/OBJECTIVES: To identify modifiable risk factors for type 2 diabetes mellitus and explore the relationship between diet sodium intake and blood glucose levels. MATERIALS/METHODS: Based on inclusion and exclusion criteria, we extracted, analyzed, and assessed the available crossover studies of dietary salt intake restriction and insulin resistance in PubMed, Web of Science, MEDLINE, Embase, Wanfang, and CNKI databases. RESULTS: We included 6 studies with 8 sets of data, covering 485 subjects. I2 statistics results showed insignificant heterogeneity among all data (I2 = 39.2% < 50%). Thus, a fixed-effect model was adopted for the final pooled effect size. Weighted mean difference and its 95% confidence interval (CI) value was 0.193 (95% CI, 0.129-0.257), and the test of the overall effect showed P < 0.001. The results revealed that the blood glucose levels in the subjects in the low-salt intake group were significantly higher than those in the normal or high-salt intake groups. We also found no significant change occurred after the removal of any study through sensitivity analysis, which confirmed that the outcome we calculated was prudent and credible. The quantitative Egger's test (P = 0.109 > 0.05) indicated that insignificant publication bias existed. CONCLUSION: This meta-analysis highlights the relationship between dietary sodium intake and blood glucose levels. Our findings show that higher blood glucose levels might be expected in hypertensive or normal people with low-salt consumption compared to those with normal or high-salt consumption, although these differences were not clinically significant. Trial Registration: PROSPERO Identifier: CRD42021256998.

10.
Environ Sci Pollut Res Int ; 30(2): 4044-4061, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35963970

RESUMO

Environmental perception is an important research direction of coal mine sustainable development. There is much dust in the underground working environment of coal mine. This study is to identify the marker (ball) in the coal mine, which provides a basic to convert the coordinate of large-scale fully mechanized mining face point cloud to the geodetic coordinate. Firstly, in the face of the phenomenon that the uneven distribution of underground point cloud is more serious, this study further has studied on the basis of complete and incomplete geometry point cloud and generated multi-density geometry point cloud for the first time. Secondly, aiming at the problem that the geometric features of underground point cloud are not obvious enough, this study has increased the weight of point cloud normal vector in the training process of network model, so that the network model is more sensitive to different geometric features. Finally, this study has used a variety of advanced deep neural networks to directly analyze point clouds to verify the proposed method. The results show that the method proposed in this study has been combined with the dynamic graph convolution neural network (DGCNN) established earlier, which can more accurately identify the ball in tens of millions of the point clouds of coal mining process. Most importantly, this work is not only of great significance to improve the production efficiency and safety in fully mechanized mining face but also lays a foundation for realizing intelligence in the mining field and avoiding the harm of dust explosion and other accidents to workers.


Assuntos
Minas de Carvão , Exposição Ocupacional , Humanos , Poeira/análise , Redes Neurais de Computação , Carvão Mineral/análise
11.
J Biol Chem ; 298(12): 102663, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36372231

RESUMO

Theoretical work suggests that collective spatiotemporal behavior of integral membrane proteins should be modulated by boundary lipids sheathing their membrane anchors. Here, we show evidence for this prediction while investigating the mechanism for maintaining a steady amount of the active form of integral membrane protein Lck kinase (LckA) by Lck trans-autophosphorylation regulated by the phosphatase CD45. We used super-resolution microscopy, flow cytometry, and pharmacological and genetic perturbation to gain insight into the spatiotemporal context of this process. We found that LckA is generated exclusively at the plasma membrane, where CD45 maintains it in a ceaseless dynamic equilibrium with its unphosphorylated precursor. Steady LckA shows linear dependence, after an initial threshold, over a considerable range of Lck expression levels. This behavior fits a phenomenological model of trans-autophosphorylation that becomes more efficient with increasing LckA. We then challenged steady LckA formation by genetically swapping the Lck membrane anchor with structurally divergent ones, such as that of Src or the transmembrane domains of LAT, CD4, palmitoylation-defective CD4 and CD45 that were expected to drastically modify Lck boundary lipids. We observed small but significant changes in LckA generation, except for the CD45 transmembrane domain that drastically reduced LckA due to its excessive lateral proximity to CD45. Comprehensively, LckA formation and maintenance can be best explained by lipid bilayer critical density fluctuations rather than liquid-ordered phase-separated nanodomains, as previously thought, with "like/unlike" boundary lipids driving dynamical proximity and remoteness of Lck with itself and with CD45.


Assuntos
Proteína Tirosina Quinase p56(lck) Linfócito-Específica , Processamento de Proteína Pós-Traducional , Antígenos Comuns de Leucócito/metabolismo , Bicamadas Lipídicas/metabolismo , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Fosforilação , Domínios Proteicos
12.
J Gene Med ; 24(8): e3440, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35816558

RESUMO

BACKGROUND: Hepatocellular cancer (HCC) is a lethal malignancy with extremely poor prognosis. In the present study, we aimed to investigate the role and underlying mechanism of SNHG1 in HCC progression. METHODS: Combined with bioinformatics and experimental validation, we explored the clinical significance of SNHG1 in HCC. A Cell Counting Kit-8 assay, cell colony formation assay, and subcutaneous tumorigenesis experiments of nude mice were conducted to evaluate the pro-proliferative capacity of SNHG1. Glucose consumption and lactate production were measured to explore the regulatory role of SNHG1 in glycolysis. Nuclear-cytoplasmic separation, quantitative real-time polymerase chain reaction and Western blot assays, chromatin immunoprecipitation, and luciferase reporter and RNA immunoprecipitation assays were performed to investigate the molecular mechanisms of SNHG1 in HCC. RESULTS: SNHG1 expression was dramatically increased in HCC and positively correlated with poor prognosis. E2F1 bound to the SNHG1 promoter region to activate SNHG1 transcription. Furthermore, SNHG1 served as a molecular sponge for miR-326 to sequester the interaction of miR-326 and pyruvate kinase M2 (PKM2), facilitating the expression of PKM2. Activating PKM2 expression was revealed to be one of mechanisms of SNHG1 with respect to promoting glycolysis and the proliferation of HCC cells. CONCLUSIONS: E2F1-activated SNHG1 modulates the miR-326/PKM2 axis to facilitate glycolysis and the proliferation of HCC cells. Targeting SNHG1 could be a promising therapeutic option for HCC.


Assuntos
Carcinoma Hepatocelular , Leucemia Mieloide Aguda , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante/metabolismo , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glicólise/genética , Humanos , Leucemia Mieloide Aguda/genética , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Piruvato Quinase/genética , Piruvato Quinase/metabolismo , RNA Longo não Codificante/genética
13.
ACS Omega ; 7(6): 4892-4907, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35187309

RESUMO

In the process of coal mining, a certain amount of gas will be produced. Environmental perception is very important to realize intelligent and unmanned coal mine production and operation and to reduce the accident rate of gas explosion and other disasters. The identification of geometric features of the coal mine working face is the main part of the environmental perception of the working face. In this study, we identify geometric features in a large-scale coal mine working face point cloud (we take the ball as an example) so as to provide a method for the environmental perception of the coal mine working face. On the basis of previous research, we upgrade the dynamic graph convolution neural network (DGCNN) for directly processing point clouds from two aspects: extracting local features and global features of point clouds. First, a multiscale dynamic graph convolution neural network (MS-DGCNN) is proposed, and the combination of max-pooling and average-pooling is used as the symmetry function. Second, we use MS-DGCNN to learn the features of a variety of geometric point clouds in the point cloud data set we make and then look for the ball in the large-scale point cloud of the coal mining working face. Finally, we compare the performance of MS-DGCNN with that of other deep neural networks directly processing point clouds. This study enables MS-DGCNN to obtain more powerful feature expression ability and enhance the generalization of the model. In addition, this study provides a solid foundation for the geometric feature identification of MS-DGCNN in the environmental perception of the coal mine working face and creates a precedent for the application of MS-DGCNN in the field of energy. At the same time, this study makes a beneficial exploration for the development of a transparent coal mine working face.

14.
ACS Omega ; 6(47): 31699-31715, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34869994

RESUMO

The intersection line information of the point cloud between the coal wall and the roof can not only accurately reflect the direction information of the scraper conveyor but also provide a preliminary basis for realizing the intelligent coal mine. However, the indirect method of using deep learning to segment the point cloud of coal mine working face cannot make full use of the rich information provided by the point cloud data. The direct method of using deep learning to segment the point cloud ignores the local feature relationship between points. Therefore, we propose to use dynamic graph convolution neural networks (DGCNNs) to segment the point cloud of the coal wall and roof so as to obtain the intersection line between them. First, in view of the characteristics of heavy dust and strong electromagnetic interference in the environment of the coal mine working face, we have installed an underground inspection robot so that we use light detection and ranging to obtain the point cloud of the coal mine working face. At the same time, we put forward a fast labeling method of the point cloud of the coal mine working face and an efficient training method of the depth neural network. Second, on the basis of edge convolution, being the greatest innovation of DGCNNs, we analyze the influence of the number of layers, K value, and output feature dimension of edge convolution on the effect of DGCNNs segmenting the point cloud of the coal mine working face and obtaining the intersection line of the coal wall and roof. Finally, we compare DGCNNs with PointNet and PointNet++. The results show that the DGCNN exhibits the best performance. What is more, the results provide a research foundation for the application of DGCNNs in the field of energy. Last but not least, the research results provide a direct and key basis for the adjustment of the scraper conveyor, which is of great significance for an intelligent coal mine working face and accurate construction of a geological information model.

15.
J Vet Res ; 65(3): 341-349, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34917848

RESUMO

INTRODUCTION: In our study, we evaluated the beneficial effect of luteolin in the treatment of cognitive dysfunction in rat models induced by cerebral hypoperfusion by two-vessel occlusion (2-VO). MATERIAL AND METHODS: Seventy-five male Sprague Dawley rats were subjected to 2-VO surgery, in all but 15 (the sham group, group I) the ligation being permanent to impair cognitive abilities. The sham group rats received saline instead of a drug; 15 2-VO rats were not injected at all (the model group, group II); 15 2-VO rats were administered luteolin at 50 mg/kg b.w. (the lut 50 group, group III); to a further 15 luteolin was given at 100 mg/kg b.w. (the lut 100 group, group IV); and the final 15 received nimodipine at 16 mg/kg b.w. as positive controls (the nimodipine group, group V). Object recognition and Morris water maze tests were performed to investigate memory ability. A Western blot test was also conducted to assess expression of phosphatidylinositol 3-kinase (PI3K), its downstream target protein kinase B (Akt), and the phosphorylated form (P-Akt) in cerebral cortex and hippocampus tissue samples. RESULTS: Significant variations in the discrimination index in the object recognition test, the escape latencies in the Morris water maze test, and expression levels of PI3K-p110α and PI3K-p85 were observed three months after 2-VO surgery in both lut groups, with a significant change in the nimodipine group compared to the model group. P-Akt and Akt were expressed significantly higher in both lut groups and the nimodipine group than in the model group. CONCLUSION: Luteolin treatment of rats cognitively dysfunctional after experimental cerebral hypo perfusion was neuroprotective by activating the PI3K/Akt signals which inhibit neuronal death in the cerebral cortex and hippocampal region.

16.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(5): 524-530, 2021 Oct 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34636199

RESUMO

OBJECTIVES: To compare the effects of different irradiators on the establishment of osteoradionecrosis of jaw model (ORNJ) to explore an ideal modeling method. METHODS: A total of 33 adult SD rats were included and randomly divided into three groups according to the radiation equipment, namely, the blank control (CN, 3 rats), group A (linear accelerator irradiation, 15 rats), and group B (small-animal irradiator irradiation, 15 rats). Groups A and B were irradiated with daily fractions of 7, 8, and 9 Gy for 5 days and further divided into three subgroups as follows: group A35/B35, 35 Gy; group A40/B40, 40 Gy; and group A45/B45, 45 Gy. The left mandibular molars of the rats were extracted 1 week after irradiation. The rats were sacrificed 3 weeks after tooth extraction, and the mandible specimens were obtained for gross observation, micro-CT scanning, and histological detection to evaluate the success rate of modeling. RESULTS: At 3 weeks after dental extractions, complete gingival healing was found in the regions of dental extractions in groups A35 and A40. However, failed gingival healing and bone exposure were found in groups A45 and B. Hematoxylin and eosin staining showed necrotic bone of the irradiated mandible in groups A40, A45,and B, with success modeling rates of 40% in group A and 93.3% in group B. CONCLUSIONS: Small-animal irradiator irradiation is an ideal device for establishing ORNJ model.


Assuntos
Osteorradionecrose , Animais , Mandíbula , Dente Molar , Osteorradionecrose/etiologia , Ratos , Ratos Sprague-Dawley , Microtomografia por Raio-X
17.
Sci Rep ; 11(1): 15175, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312475

RESUMO

Splicing factors (SFs) play critical roles in the pathogenesis of various cancers through regulating tumor-associated alternative splicing (AS) events. However, the clinical value and biological functions of SFs in hepatocellular carcinoma (HCC) remain obscure. In this study, we identified 40 dysregulated SFs in HCC and established a prognostic model composed of four SFs (DNAJC6, ZC3H13, IGF2BP3, DDX19B). The predictive efficiency and independence of the prognostic model were confirmed to be satisfactory. Gene Set Enrichment Analysis (GSEA) illustrated the risk score calculated by our prognostic model was significantly associated with multiple cancer-related pathways and metabolic processes. Furthermore, we constructed the SFs-AS events regulatory network and extracted 108 protein-coding genes from the network for following functional explorations. Protein-protein interaction (PPI) network delineated the potential interactions among these 108 protein-coding genes. GO and KEGG pathway analyses investigated ontology gene sets and canonical pathways enriched by these 108 protein-coding genes. Overlapping the results of GSEA and KEGG, seven pathways were identified to be potential pathways regulated by our prognostic model through triggering aberrant AS events in HCC. In conclusion, the present study established an effective prognostic model based on SFs for HCC patients. Functional explorations of SFs and SFs-associated AS events provided directions to explore biological functions and mechanisms of SFs in HCC tumorigenesis.


Assuntos
Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , Processamento Alternativo , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Modelos Biológicos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas de Transporte Nucleocitoplasmático/genética , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Prognóstico , Mapas de Interação de Proteínas/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Fatores de Risco
18.
Sci Rep ; 11(1): 9605, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953213

RESUMO

The objective of this study was to propose a new method for facilitating needle-beam alignment ultrasound-guided in-plane catheterization of the subclavian vein (SCV). Three hundred patients were recruited, and ultrasound examination of the SCV was performed. Then, the patients were divided into two groups and SCV catheterization was performed: ultrasound-guided catheterization with the aiming method (group A) and ultrasound-guided catheterization with needle guide (group NG). The success rate, insertion time, number of skin breaks, number of needle redirections, needle visibility and rate of mechanical complications were documented and compared for each procedure. To depict the optimum long-axis view of the SCV, there was a 30° ± 7.3° angle (rotation) between the long axis of the ultrasound probe and the clavicle, while there was a 39° ± 7.4° angle (tilt) between the ultrasound beam plane and the right chest wall. The aiming method was associated with fewer skin breaks [(mean (IQR): 1 (1-1) times vs 1 (1-2) times, P = 0.009], a shorter time to cannulation [(mean (IQR): 39 (32-48.5) s vs 48 (44-54.8) s, P = 0.000] and more needle redirections [(mean (IQR): 0 (0-1) vs 0 (0-0), P = 0.000]. There were no differences between group A and group NG in the overall success rate, first puncture success rate, needle visibility or mechanical complication rate. In conclusion, during ultrasound-guided in-plane catheterization of the SCV, the aiming method provides comparable needle-beam alignment with a lower cannulation time than the needle guide technique.


Assuntos
Cateterismo/métodos , Veia Subclávia/cirurgia , Ultrassonografia de Intervenção/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Veia Subclávia/diagnóstico por imagem
19.
Biophys J ; 120(9): 1692-1704, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33730552

RESUMO

To accomplish their critical task of removing infected cells and fighting pathogens, leukocytes activate by forming specialized interfaces with other cells. The physics of this key immunological process are poorly understood, but it is important to understand them because leukocytes have been shown to react to their mechanical environment. Using an innovative micropipette rheometer, we show in three different types of leukocytes that, when stimulated by microbeads mimicking target cells, leukocytes become up to 10 times stiffer and more viscous. These mechanical changes start within seconds after contact and evolve rapidly over minutes. Remarkably, leukocyte elastic and viscous properties evolve in parallel, preserving a well-defined ratio that constitutes a mechanical signature specific to each cell type. Our results indicate that simultaneously tracking both elastic and viscous properties during an active cell process provides a new, to our knowledge, way to investigate cell mechanical processes. Our findings also suggest that dynamic immunomechanical measurements can help discriminate between leukocyte subtypes during activation.


Assuntos
Leucócitos , Elasticidade , Viscosidade
20.
Sci Rep ; 11(1): 1599, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452406

RESUMO

The objective of this study was to identify the factors that complicate the needle visualization in ultrasound-guided in-plane needling procedures. Forty-nine residents were recruited and randomized to insert the simulated blood vessel with four different views including Neutral (the long axis of the probe along the visual axis and the ultrasonic beam vertical to the surface of gel phantom), 45°-rotation (45° angle between the long axis of probe and the operator's visual axis), 45°-tilt (45° angle between the ultrasonic beam and the surface of gel phantom) and 45°-rotation plus 45°-tilt of probe. Number of needle redirections, insertion time, and needle visibility were documented and compared for each procedure. When the residents faced with 45°-tilt view, the needle redirections (2 vs 0) and insertion time increased significantly (39 vs 16) compared with that of the Neutral view. When faced with 45°-rotation plus 45°-tilt view, the residents' performance decreased further as compared with that of the 45°-tilt view and the Neutral view. However, there was no performance difference between the Neutral view and 45°-rotation view. In conclusion, during ultrasound-guided in-plane procedures, tilting the ultrasound probe may increase the difficulty of needle-beam alignment.

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