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1.
J Clin Oncol ; : JCO2201450, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36735896

RESUMO

PURPOSE: Immune checkpoint inhibitors combined with antiangiogenic therapy reportedly have potential synergistic antitumor activity. We investigated the activity and safety of this regimen for recurrent/metastatic nasopharyngeal carcinoma (NPC). METHODS: This single-arm, Simon two-stage study enrolled patients with recurrent/metastatic NPC who were refractory to at least first-line systemic therapy and treatment-naive to immune checkpoint inhibitors. The patients received camrelizumab 200 mg once every 3 weeks and apatinib 250 mg once per day. The primary end point was the objective response rate. Key secondary end points included disease control rate, progression-free survival, duration of response, overall survival, and safety. RESULTS: Between October 14, 2020, and December 23, 2021, 58 patients were enrolled, and all were included in the efficacy and safety analysis set. The objective response rate was 65.5% (95% CI, 51.9 to 77.5), and the disease control rate was 86.2% (95% CI, 74.6 to 93.9). The median duration of response was not reached, and the median progression-free survival was 10.4 months (95% CI, 7.2 to 13.6), with a median follow-up duration of 12.4 months (range, 2.1-19.9 months). Treatment-related adverse events (TRAEs) of grade 3 or higher were reported in 34 (58.6%) patients, with the most common being hypertension (19.0%), nasopharyngeal necrosis (15.5%), headache (12.1%), AST elevation (10.3%), and creatine phosphokinase elevation (10.3%). Sixteen (27.6%) patients discontinued apatinib treatment before progression because of unbearable TRAEs, and the most common complication was nasopharyngeal necrosis (9/16; 56.3%). Recurrent nasopharyngeal lesions (odds ratio, 5.94 [95% CI, 1.45 to 24.24]) and reirradiation (odds ratio, 5.33 [95% CI, 1.15 to 24.79]) were significantly positively correlated with nasopharyngeal necrosis. CONCLUSION: Camrelizumab plus apatinib had promising antitumor activity in patients with refractory recurrent/metastatic NPC who failed first-line therapy. Moderate to severe TRAEs were experienced by 58.6%, including nasopharyngeal necrosis associated with local recurrence and a history of reirradiation.

2.
Metallomics ; 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36737500

RESUMO

Synchrotron X-ray fluorescence microscopy (SXRF) presents a valuable opportunity to study the metallome of single cells because it simultaneously provides high resolution subcellular distribution and quantitative cellular content of multiple elements. Different sample preparation techniques have been used to preserve cells for observations with SXRF, with a goal to maintain fidelity of the cellular metallome. In this case study, mouse pancreatic beta-cells have been preserved with optimized chemical fixation. We show that cell-to-cell variability is normal in the metallome of beta-cells due to heterogeneity and should be considered when interpreting SXRF data. In addition, we determined the impact of several immunofluorescence protocols (IF) on metal distribution and quantification in chemically fixed beta-cells and found that the metallome of beta-cells was not well preserved for quantitative analysis. However, zinc and iron qualitative analysis could be performed after IF with certain limitations. To help minimize metal loss using samples that require IF, we describe a novel IF protocol that can be used with chemically fixed cells after the completion of SXRF.

3.
J Appl Clin Med Phys ; : e13924, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36729737

RESUMO

OBJECTIVES: To explore the influence of the surrounding environment of the target tissue, lesion size, and rectangular sampling box size on shear wave speed (SWS). METHODS: The tendon SWS was acquired ex-vivo. Then the tendons were dissected and buried in the couplant (gel) and evaluated by two-dimensional shear wave elastography (2D-SWE). Finally, the tendons were placed in the isolated muscles to simulate the intramuscular lesions, and their elasticity was tested under two rectangular sampling box conditions. The isolated complete liver SWS was acquired. Similarly, the large and small pieces of livers were cut out, placed in the muscles, and assessed by SWE under two rectangular sampling box conditions. The SWS acquired under different conditions was compared. Variability was evaluated using the coefficient of variation (CV). The intraclass correlation coefficient (ICC) was used to evaluate repeatability. RESULTS: The SWS of the tendons ex-vivo, buried in the couplant and placed in the isolated muscles showed significant differences (p < 0.001). The ex-vivo condition produced the highest SWS and CV values. There were significant differences in SWS of livers with different sizes placed in muscles (p < 0.001). The highest SWS value was associated with small pieces of livers. No significant difference was found in SWS acquired under different rectangular box sizes (p > 0.05). CONCLUSIONS: Under the present study conditions, the surrounding environment of the target tissue makes a big difference to lesion SWS values. The lesion size will affect the assessment of its inherent elasticity. The size of the sampling frame has no significant effect on the tissue SWS.

4.
BMC Cancer ; 23(1): 88, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36698118

RESUMO

BACKGROUND: Magnetic resonance imaging (MRI) performs well in the locoregional assessment of extranodal nasal-type NK/T-cell lymphoma (ENKTCL). It's important to assess the value of multi-modal MRI-based radiomics for estimating overall survival (OS) in patients with ENKTCL. METHODS: Patients with ENKTCL in a prospectively cohort were systemically reviewed and all the pretreatment MRI were acquisitioned. An unsupervised spectral clustering method was used to identify risk groups of patients and radiomic features. A nomogram-revised risk index (NRI) plus MRI radiomics signature (NRI-M) was developed, and compared with the NRI. RESULTS: The 2 distinct type I and II groups of the MRI radiomics signatures were identified. The 5-year OS rates between the type I and type II groups were 87.2% versus 67.3% (P = 0.002) in all patients, and 88.8% versus 69.2% (P = 0.003) in early-stage patients. The discrimination and calibration of the NRI-M for OS prediction demonstrated a better performance than that of either MRI radiomics or NRI, with a mean area under curve (AUC) of 0.748 and 0.717 for predicting the 5-year OS in all-stages and early-stage patients. CONCLUSIONS: The NRI-M model has good performance for predicting the prognosis of ENKTCL and may help design clinical trials and improve clinical decision making.


Assuntos
Linfoma Extranodal de Células T-NK , Linfoma de Células T , Humanos , Prognóstico , Imageamento por Ressonância Magnética/métodos , Nomogramas , Medição de Risco , Estudos Retrospectivos , Linfoma Extranodal de Células T-NK/diagnóstico por imagem , Linfoma Extranodal de Células T-NK/patologia
5.
Materials (Basel) ; 16(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614786

RESUMO

In this paper, the residual stresses with a nanoscale depth resolution at TSV-Cu/TiW/SiO2/Si interfaces under different thermal loadings are characterized using the ion-beam layer removal (ILR) method. Moreover, the correlations of residual stress, microstructure, and the failure modes of the interfaces are discussed. The residual stresses at the interfaces of TSV-Cu/TiW, TiW/SiO2, and SiO2/Si are in the form of small compressive stress at room temperature, then turn into high-tensile stress after thermal cycling or annealing. In addition, the maximum residual stress inside the TSV-Cu is 478.54 MPa at room temperature, then decreases to 216.75 MPa and 90.45 MPa, respectively, after thermal cycling and annealing. The microstructural analysis indicates that thermal cycling causes an increase in the dislocation density and a decrease in the grain diameter of TSV-Cu. Thus, residual stress accumulates constantly in the TSV-Cu/TiW interface, resulting in the cracking of the interface. Furthermore, annealing leads to the cracking of more interfaces, relieving the residual stress as well as increasing the grain diameter of TSV-Cu. Besides this, the applicability of the ILR method is verified by finite element modeling (FEM). The influence of the geometric errors of the micro-cantilever beam and the damage to the materials introduced by the focused ion beam (FIB) in the experimental results are discussed.

6.
Adv Mater ; : e2208256, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36634150

RESUMO

Emerging piezocatalysts have demonstrated their remarkable application potentials in diverse medical fields. In addition to their ultrahigh catalytic activities, their inherent and unique charge carrier-releasing properties can be used to initiate various redox catalytic reactions, displaying bright prospects for future medical applications. Triggered by mechanical energy, piezocatalytic materials can release electrons/holes, catalyze redox reactions of substrates or intervene in biological processes to promote the production of effector molecules for medical purposes, such as decontamination, sterilization, and therapy. Such a medical application of piezocatalysis is termed as piezocatalytic medicine (PCM) herein. To pioneer novel medical technologies, especially therapeutic modalities, this review provides an overview of the state-of-the-art research progresses in piezocatalytic medicine. First, the principle of piezocatalysis and the preparation methodologies of piezoelectric materials will be introduced. Then, we provide a comprehensive summary of the medical applications of piezocatalytic materials in tumor treatment, antisepsis, organic degradation, tissue repair and regeneration, and biosensing. Finally, the main challenges and future perspectives in piezocatalytic medicine are discussed and proposed, expecting to fuel the development of this emerging scientific discipline. This article is protected by copyright. All rights reserved.

7.
Microbiol Spectr ; : e0358522, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36602316

RESUMO

Gut symbiotic bacteria are known to be closely related to insect development, nutrient metabolism, and disease resistance traits, but the most important factors leading to changes in these communities have not been well clarified. To address this, we examined the associations between the gut symbiotic bacteria and the host genotype and geographical distribution of Solenopsis invicta in China, where it is invasive and has spread primarily by human-mediated dispersal. Thirty-two phyla were detected in the gut symbiotic bacteria of S. invicta. Proteobacteria were the most dominant group among the gut symbiotic bacteria. Furthermore, the Bray-Curtis dissimilarity matrices of the gut symbiotic bacteria were significantly positively correlated with the geographical distance between the host ant colonies, but this relationship was affected by the social form. The distance between monogyne colonies had a significant effect on the Bray-Curtis dissimilarity matrices of gut symbiotic bacteria, but the distance between polygyne colonies did not. Moreover, the Bray-Curtis dissimilarity matrices were positively correlated with Nei's genetic distance of the host but were not correlated with the COI-based genetic distance. This study provides a scientific basis for further understanding the ecological adaptability of red imported fire ants during invasion and dispersal. IMPORTANCE We demonstrated that gut microbiota composition and diversity varied among populations. These among-population differences were associated with host genotype and geographical distribution. Our results suggested that population-level differences in S. invicta gut microbiota may depend more on environmental factors than on host genotype.

8.
Anal Chem ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36622664

RESUMO

Adenosine triphosphate (ATP), as an indispensable biomolecule, is the main energy source of cells and is used as a marker for diseases such as cancer and fatty liver. It is of great significance to design a near-infrared fluorescent nanoprobe with excellent performance and apply it to various disease models. Here, a near-infrared fluorescent nanoprobe (ZIF-90@SiR) based on a zeolitic imidazole framework is proposed. The fluorescent nanoprobes are synthesized by encapsulating the dye (SiR) into the framework of ZIF-90. Upon the addition of ATP, the structure of the ZIF-90@SiR nanoprobe is disrupted and SiR is released to generate near-infrared fluorescence at 670 nm. In the process of ATP detection, ZIF-90@SiR shows high sensitivity and good selectivity. Moreover, the ZIF-90@SiR nanoprobe has good biocompatibility due to its low toxicity to cells. It is used for fluorescence imaging of ATP in living cells and thus distinguishing normal cells and cancer cells, as well as distinguishing fatty liver cells. Due to excellent near-infrared fluorescence properties, the ZIF-90@SiR nanoprobe can not only distinguish normal mice and tumor mice but also differentiate normal mice and fatty liver mice for the first time.

9.
J Nanobiotechnology ; 21(1): 18, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650517

RESUMO

The occurrence of osteoarthritis (OA) is highly correlated with the reduction of joint lubrication performance, in which persistent excessive inflammation and irreversible destruction of cartilage dominate the mechanism. The inadequate response to monotherapy methods, suboptimal efficacy caused by undesirable bioavailability, short retention, and lack of stimulus-responsiveness, are few unresolved issues. Herein, we report a pH-responsive metal-organic framework (MOF), namely, MIL-101-NH2, for the co-delivery of anti-inflammatory drug curcumin (CCM) and small interfering RNA (siRNA) for hypoxia inducible factor (HIF-2α). CCM and siRNA were loaded via encapsulation and surface coordination ability of MIL-101-NH2. Our vitro tests showed that MIL-101-NH2 protected siRNA from nuclease degradation by lysosomal escape. The pH-responsive MIL-101-NH2 gradually collapsed in an acidic OA microenvironment to release the CCM payloads to down-regulate the level of pro-inflammatory cytokines, and to release the siRNA payloads to cleave the target HIF-2α mRNA for gene-silencing therapy, ultimately exhibiting the synergetic therapeutic efficacy by silencing HIF-2α genes accompanied by inhibiting the inflammation response and cartilage degeneration of OA. The hybrid material reported herein exhibited promising potential performance for OA therapy as supported by both in vitro and in vivo studies and may offer an efficacious therapeutic strategy for OA utilizing MOFs as host materials.


Assuntos
Curcumina , Estruturas Metalorgânicas , Osteoartrite , Humanos , Curcumina/farmacologia , Condrócitos/metabolismo , RNA Interferente Pequeno/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Inflamação/metabolismo , Concentração de Íons de Hidrogênio
10.
Can Pharm J (Ott) ; 156(1): 42-47, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36686314

RESUMO

Background: Drug-drug interactions are preventable medication errors that can lead to serious negative outcomes for patients. Community pharmacists are uniquely positioned with their medication knowledge and role in prescription clinical assessment. However, workplace pressures and limitations related to computer systems can lead to drug-drug interactions being missed. There is a lack of information as to how community pharmacists assess drug interactions. Methods: A qualitative study using key informant interviews of community pharmacists was conducted. Pharmacists were questioned on their perceptions and views of drug interactions. Results: Eight community pharmacists participated. Four main themes were identified from the interviews: 1) pharmacist process of identifying drug interactions, 2) tools that help pharmacists assess and respond to drug interactions, 3) challenges in identifying and responding to clinically important drug interactions and 4) measures to avoid missing interactions. Discussion: Community pharmacists experience challenges around their lack of access to patient information, which limits their ability to properly assess drug-drug interactions. In addition, increasing workload pressures have affected their ability to ensure their patients receive optimal pharmaceutical care. There is also a disconnect between the community pharmacy computer systems' alerts and their clinical relevancy to their specific patients. The overall burdens can lead to professional abstinence in the assessment of drug-drug interactions. Conclusion: Community pharmacists are in an ideal position to prevent patients from experiencing drug-drug interactions. However, to further enable them to fulfill this role, increased access to patients' health records, decreased workload and better customization of computer alerts need to occur.

11.
Int J Mol Sci ; 24(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36674828

RESUMO

Pasteurella multocida can cause goat hemorrhagic sepsis and endemic pneumonia. Respiratory epithelial cells are the first line of defense in the lungs during P. multocida infection. These cells act as a mechanical barrier and activate immune response to protect against invading pathogenic microorganisms. Upon infection, P. multocida adheres to the cells and causes changes in cell morphology and transcriptome. ATAC-seq was conducted to determine the changes in the chromatin open region of P. multocida-infected goat bronchial epithelial cells based on transcriptional regulation. A total of 13,079 and 28,722 peaks were identified in the control (CK) and treatment (T) groups (P. multocida infection group), respectively. The peaks significantly increased after P. multocida infection. The specific peaks for the CK and T groups were annotated to 545 and 6632 genes, respectively. KEGG pathway enrichment analysis revealed that the specific peak-related genes in the T group were enriched in immune reaction-related pathways, such as Fc gamma R-mediated phagocytosis, MAPK signaling pathway, bacterial invasion of epithelial cells, endocytosis, and autophagy pathways. Other cellular component pathways were also enriched, including the regulation of actin cytoskeleton, adherent junction, tight junction, and focal adhesion. The differential peaks between the two groups were subsequently analyzed. Compared to those in the CK group, 863 and 11 peaks were upregulated and downregulated, respectively, after the P. multocida infection. Fifty-six known transcription factor motifs were revealed in upregulated peaks in the P. multocida-infected group. By integrating ATAC-seq and RNA-seq, some candidate genes (SETBP1, RASGEF1B, CREB5, IRF5, TNF, CD70) that might be involved in the goat bronchial epithelial cell immune reaction to P. multocida infection were identified. Overall, P. multocida infection changed the structure of the cell and caused chromatin open regions to be upregulated. In addition, P. multocida infection actively mobilized the host immune response with the inflammatory phenotype. The findings provide valuable information for understanding the regulatory mechanisms of P. multocida-infected goat bronchial epithelial cells.


Assuntos
Pasteurella multocida , Animais , Pasteurella multocida/genética , Cromatina/genética , Cabras/genética , Regulação da Expressão Gênica , Células Epiteliais
12.
Eur J Nutr ; 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717385

RESUMO

PURPOSE: To test the hypothesis that daily supplementation with low-dose B vitamins plus betaine could significantly reduce plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia and free from background mandatory folic acid fortification. METHODS: One hundred apparently healthy adults aged 18-65 years with hyperhomocysteinemia were recruited in South China from July 2019 to June 2021. They were randomly assigned to either the supplement group (daily supplementation: 400 µg folic acid, 8 mg vitamin B6, 6.4 µg vitamin B12 and 1 g betaine) or the placebo group for 12 weeks. Fasting venous blood was collected at baseline, week 4 and week 12 to determine the concentrations of homocysteine, folate, vitamin B12 and betaine. Generalized estimation equations were used for statistical analysis. RESULTS: Statistically significant increments in blood concentrations of folate, vitamin B12 and betaine after the intervention in the supplement group indicated good participant compliance. At baseline, there were no significant differences in plasma homocysteine concentration between the two groups (P = 0.265). After 12-week supplementation, compared with the placebo group, there was a significant reduction in plasma homocysteine concentrations in the supplement group (mean group difference - 3.87; covariate-adjusted P = 0.012; reduction rate 10.1%; covariate-adjusted P < 0.001). In the supplement group, the decreased concentration of plasma homocysteine was associated with increments of blood concentrations of both folate (ß = -1.680, P = 0.004) and betaine (ß = -1.421, P = 0.020) after 12 weeks of supplementation. CONCLUSIONS: Daily supplementation with low-dose B vitamins plus betaine for 12 weeks effectively decreased plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT03720249 on October 25, 2018. Website: https://clinicaltrials.gov/ct2/show/NCT03720249 .

13.
Sci Rep ; 13(1): 1667, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717583

RESUMO

Together, the Yinggehai and Qiongdongnan basins have received a large amount of terrigenous sediments, but the provenance evolution of Cenozoic sediments in the two basins remains disputable. Combined with previous studies in the Yinggehai and Qiongdongnan basins, the elemental geochemistry of Oligocene to Pliocene sediment samples in the junction area of the two basins were analyzed to explore the tectonic implications, parent rock characteristics, and provenance evolution of the two basins during the Cenozoic. The results reveal that all the sediment samples were derived from continental island arc to passive continental margin settings. The light REE enrichment and stable content of heavy REE with large negative Eu anomalies indicate that they were probably derived from Hainan Island. The reconstructed provenance evolution model showed that the Red River Source (RRS) provided sedimentary materials for the Central Depression of Yinggehai Basin from the Oligocene to the Pliocene, and Hainan Island Source (HIS) was also one of the sources for sediments deposited in the Central Depression of Yinggehai Basin during the Miocene. However, most of the sediments preserved in the Yingdong Slope and Qiongdongnan Basin were derived from the HIS from the Oligocene to the Pliocene, and sediments deposited in the Yingdong Slope were also derived from the RRS during the Miocene. Furthermore, the junction area of the two basins had a mixed source of the RRS and HIS during the Cenozoic.

15.
BMC Oral Health ; 23(1): 16, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631872

RESUMO

BACKGROUND: Machine learning based auto-segmentation of 3D images has been developed rapidly in recent years. However, the application of this new method in the research of patients with unilateral cleft lip and palate (UCLP) is very limited. In this study, a machine learning algorithm utilizing 3D U-net was used to automatically segment the maxilla, fill the cleft and evaluate the alveolar bone graft in UCLP patients. Cleft related factors and the surgery impact on the development of maxilla were analyzed. METHODS: Preoperative and postoperative computed tomography images of 32 patients (64 images) were obtained. The deep-learning-based protocol was used to segment the maxilla and defect, followed by manual refinement. Paired t-tests and Mann-Whitney tests were performed to reveal the changes of the maxilla after surgery. Two-factor, two-level analysis for repeated measurement was used to examine the different trends of growth on the cleft and non-cleft sides of the maxilla. Pearson and Spearman correlations were used to explore the relationship between the defect and the changes of the maxillary cleft side. RESULTS: One-year after the alveolar bone grafting surgery, different growth amount was found on the cleft and non-cleft sides of maxilla. The maxillary length (from 34.64 ± 2.48 to 35.67 ± 2.45 mm) and the alveolar length (from 36.58 ± 3.21 to 37.63 ± 2.94 mm) increased significantly only on the cleft side while the maxillary anterior width (from 11.61 ± 1.61 to 12.01 ± 1.41 mm) and posterior width (from 29.63 ± 2.25 to 30.74 ± 2.63 mm) increased significantly only on the non-cleft side after surgery. Morphology of the cleft was found to be related to the pre-surgical maxillary dimension on the cleft side, while its correlation with the change of the maxilla after surgery was low or not statistically significant. CONCLUSION: The auto-segmentation of the maxilla and the cleft could be performed very efficiently and accurately with the machine learning method. Asymmetric growth was found on the cleft and non-cleft sides of the maxilla after alveolar bone graft in UCLP patients. The morphology of the cleft mainly contributed to the pre-operation variance of the maxilla but had little impact on the maxilla growth after surgery.


Assuntos
Enxerto de Osso Alveolar , Fenda Labial , Fissura Palatina , Humanos , Fissura Palatina/diagnóstico por imagem , Fissura Palatina/cirurgia , Maxila/diagnóstico por imagem , Maxila/cirurgia , Fenda Labial/diagnóstico por imagem , Fenda Labial/cirurgia , Enxerto de Osso Alveolar/métodos , Tomografia Computadorizada por Raios X
16.
BMC Oral Health ; 23(1): 28, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650491

RESUMO

BACKGROUND: It is difficult for orthodontists to accurately predict the growth trend of the mandible in children with anterior crossbite. This study aims to develop a deep learning model to automatically predict the mandibular growth result into normal or overdeveloped using cephalometric radiographs. METHODS: A deep convolutional neural network (CNN) model was constructed based on the algorithm ResNet50 and trained on the basis of 256 cephalometric radiographs. The prediction behavior of the model was tested on 40 cephalograms and visualized by equipped with Grad-CAM. The prediction performance of the CNN model was compared with that of three junior orthodontists. RESULTS: The deep-learning model showed a good prediction accuracy about 85%, much higher when compared with the 54.2% of the junior orthodontists. The sensitivity and specificity of the model was 0.95 and 0.75 respectively, higher than that of the junior orthodontists (0.62 and 0.47 respectively). The area under the curve value of the deep-learning model was 0.9775. Visual inspection showed that the model mainly focused on the characteristics of special regions including chin, lower edge of the mandible, incisor teeth, airway and condyle to conduct the prediction. CONCLUSIONS: The deep-learning CNN model could predict the growth trend of the mandible in anterior crossbite children with relatively high accuracy using cephalometric images. The deep learning model made the prediction decision mainly by identifying the characteristics of the regions of chin, lower edge of the mandible, incisor teeth area, airway and condyle in cephalometric images.


Assuntos
Aprendizado Profundo , Má Oclusão , Humanos , Criança , Mandíbula/diagnóstico por imagem , Redes Neurais de Computação , Radiografia , Má Oclusão/diagnóstico por imagem
17.
Mol Biol Rep ; 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36715789

RESUMO

INTRODUCTION: Diabetic nephropathy (DN) is one of the most common and lethal diabetic complications worldwide and is associated with a high risk of mortality. However, the exact mechanism behind its development is unknown. The mesangial cells (MCs) and non-coding RNAs are critical for DN, but it is unknown whether a MEG3/miR-21/ORAI1 regulatory axis exists in MCs. Hence, in this study, we aimed to understand whether the MEG3/miR-21/ORAI1 regulatory axis has a role in the pathophysiology of DN. RESULTS: We demonstrated that high-glucose stimuli downregulated MEG3 and ORAI1 expression while enhancing miR-21 expression. Exogenous miR-21 mimics inhibited ORAI1 expression, which was partially salvaged or reversed by MEG3 overexpression. Furthermore, RIP assay demonstrated that the beads labeled with AGO2 antibody could enrich more miR-21 and MEG3 than those labeled with control IgG antibody; both of them formed the RNA-induced silencing complex. Further, the biochemical indicators of db/db mice significantly improved, and renal fibrinoid necrosis was ameliorated using a miR-21 inhibitor. CONCLUSION: The MEG3/miR-21/ORAI1 axis regulates the manifestation of DN in diabetic mice and MCs, and the miR-21 inhibitor can be a potential therapeutic strategy to alleviate DN, once the presence of such an axis is found in humans.

18.
Signal Transduct Target Ther ; 8(1): 46, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717539

RESUMO

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.


Assuntos
COVID-19 , Humanos , Adulto , SARS-CoV-2 , Interleucina-8 , Citocinas
19.
Sci Adv ; 9(3): eabq1395, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36662868

RESUMO

Breast cancer-associated gene 1 (Brca1) deficiency induces the onset of breast cancer formation, accompanied with extensive genetic alterations. Here, we used both the sleeping beauty transposon mutagenesis system and CRISPR-Cas9-mediated genome-wide screening in mice to identify potential genetic alterations that act synergistically with Brca1 deficiency to promote tumorignesis. Both approaches identified Cullin-5 as a tumor suppressor, whose mutation enabled Brca1-deficient cell survival and accelerated tumorigenesis by orchestrating tumor microenvironment. Cullin-5 suppresses cell growth through ubiquitylating and degrading adenosine 3',5'-monophosphate-responsive element binding protein 1 (CREB1), especially under protein damage condition. Meanwhile, Cullin-5 deficiency activated CREB1-CCL2 signaling and resulted in the accumulation of monocytes and polymorphonuclear myeloid-derived suppressor cells, reduction of T cells that benefit tumor progression in both Brca1-deficient cells and wild-type cells. Blocking CREB1 activity either through gene knockout or specific inhibitor treatment suppressed changes in the tumor microenvironment caused by Cullin-5 deficiency and blocked tumor progression.


Assuntos
Proteínas Culina , Neoplasias Mamárias Animais , Animais , Camundongos , Proteínas Culina/genética , Genes Supressores de Tumor , Neoplasias Mamárias Animais/patologia , Transdução de Sinais , Microambiente Tumoral , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo
20.
Int J Mol Sci ; 24(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36675197

RESUMO

The tripartite motif protein 21 (TRIM21) belongs to the TRIM family, possessing an E3 ubiquitin ligase activity. Similar to other TRIMs, TRIM21 also contains three domains (named RBCC), including the Really Interesting New Gene (RING) domain, one or two B-Box domains (B-Box), and one PRY/SPRY domain. Notably, we found that the RING and B-Box domains are relatively more conservative than the PRY/SPRY domain, suggesting that TRIM21 of different species had similar functions. Recent results showed that TRIM21 participates in virus infection by directly interacting with viral proteins or modulating immune and inflammatory responses. TRIM21 also acts as a cytosol high-affinity antibody Fc receptor, binding to the antibody-virus complex and triggering an indirect antiviral antibody-dependent intracellular neutralization (ADIN). This paper focuses on the recent progress in the mechanism of TRIM21 during virus infection and the application prospects of TRIM21 on virus infection.


Assuntos
Ribonucleoproteínas , Viroses , Humanos , Citosol/metabolismo , Proteínas/metabolismo , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Viroses/genética , Viroses/metabolismo , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo
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