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1.
J Hepatocell Carcinoma ; 9: 367-377, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35535232

RESUMO

Purpose: Functional analysis was performed to elucidate the mechanism by which hepatocellular carcinoma (HCC) outcome-associated mutation in the hepatitis B virus X (HBx) gene modifies the HCC process. Methods: Proliferation, invasion, migration, and apoptosis assays were performed, and changes in fibrosis, intracellular reactive oxygen species (ROS), and cytokine levels were measured. The differences between variables were evaluated by Student's t-test. Results: The influence of two previously identified nonsynonymous mutation, C1653T and T1753C, on HCC cells was assessed. With regard to HBX-induced promotion of proliferation (p < 0.01), invasion (p < 0.01) and migration (p < 0.01), the C1653T mutation displayed a significant additive effect in these assays (P < 0.05). The subsequent apoptosis assay indicated that HBX could inhibit apoptosis (P < 0.01), whereas the C1653T mutation markedly amplified this effect in HCC cells (P < 0.01). Furthermore, the tumor growth-promoting effect of HBX was confirmed in a mouse xenograft model of HCC (P < 0.05), and the C1653T mutation was observed to amplify this effect (P < 0.05). To further investigate the mechanism by which the C1653T mutation enhances malignancy in HCC cells, fibrosis, intracellular ROS, and cytokine levels were measured. The C1653T mutant increased fibrosis and intracellular ROS level, and altered monocyte chemotactic protein-1 and interleukin-18 expression in HepG2 cells. Drug sensitivity test revealed that the C1653T mutation is sensitive to apatinib treatment and that overexpression of vascular endothelial growth factor might be involved in this process. Conclusion: Our data indicate that the C1653T mutation of HBx promotes HCC malignancy by altering the levels of fibrosis, ROS, and some cytokines. This mutation could serve as a potential biomarker for screening HCC patients to determine apatinib treatment efficacy.

2.
Sci Rep ; 12(1): 7916, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551229

RESUMO

To detect the prognostic factors associated with initial reattachment after primary pars plana vitrectomy (PPV) with air tamponade for rhegmatogenous retinal detachment (RRD). We retrospectively reviewed 92 eyes of 92 patients with RRD. All eyes underwent PPV with air tamponade and a follow-up of at least 6 months. Initial anatomical success was defined as reattachment of the retina by a single operation. We performed univariate analysis to detect the presence of any difference between eyes with a successful initial reattachment and those that failed. We also performed multivariate logistic regression analysis to assess the influence of each preoperative factor on initial success. The rate of initial reattachment success was 93.5%. The percentage of retinal detachment involving the inferior quadrants in the initial success group was less than that in the initial failure group, and the difference was statistically significant (P = 0.043). There were no significant differences noted for other factors, such as symptom duration (P = 0.078) or location of retinal breaks (P = 0.065). Multiple logistic regression analysis using preoperative factors indicated that older age (odds ratio, 0.90; 95% confidence interval, 0.82-0.97; P = 0.010) and non-involvement of inferior quadrants (odds ratio, 9.90; 95% confidence interval, 1.36-71.92; P = 0.023) were significantly associated with initial success. PPV combined with air may be an effective treatment for some simple RRDs (proliferative vitreoretinopathy [PVR] grade ≤ C1). Non-involvement of the inferior quadrants and older age at presentation are associated with a greater likelihood of anatomic success. The volume of air in the eye after surgery is also very important, which may also affect the reduction of retinal detachment.

3.
Cancer Med ; 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35441810

RESUMO

BACKGROUND: Breast cancer (BC) is the most common malignant tumor worldwide. Apoptosis and hypoxia are involved in the progression of BC, but reliable biomarkers for these have not been developed. We hope to explore a gene signature that combined apoptosis and hypoxia-related genes (AHGs) to predict BC prognosis and immune infiltration. METHODS: We collected the mRNA expression profiles and clinical data information of BC patients from The Cancer Genome Atlas database. The gene signature based on AHGs was constructed using the univariate Cox regression, least absolute shrinkage and selection operator, and multivariate Cox regression analysis. The associations between risk scores, immune infiltration, and immune checkpoint gene expression were studied using single-sample gene set enrichment analysis. Besides, gene signature and independent clinicopathological characteristics were combined to establish a nomogram. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on the potential functions of AHGs. RESULTS: We identified a 16-AHG signature (AGPAT1, BTBD6, EIF4EBP1, ERRFI1, FAM114A1, GRIP1, IRF2, JAK1, MAP2K6, MCTS1, NFKBIA, NFKBIZ, NUP43, PGK1, RCL1, and SGCE) that could independently predict BC prognosis. The median score of the risk model divided the patients into two subgroups. By contrast, patients in the high-risk group had poorer prognosis, less abundance of immune cell infiltration, and expression of immune checkpoint genes. The gene signature and nomogram had good predictive effects on the overall survival of BC patients. GO and KEGG analyses revealed that the differential expression of AHGs may be closely related to tumor immunity. CONCLUSION: We established and verified a 16-AHG BC signature which may help predict prognosis, assess potential immunotherapy benefits, and provide inspiration for future research on the functions and mechanisms of AHGs in BC.

4.
Front Pharmacol ; 13: 817662, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431928

RESUMO

Backgrounds: Immune checkpoint inhibitors (ICIs) are considered cornerstones of oncology treatment with durable anti-tumor efficacy, but the increasing use of ICIs is associated with the risk of developing immune-related adverse events (irAEs). Although ICI-associated pancreatic adverse events (AEs) have been reported in patients treated with ICIs, the clinical features and spectrum of pancreatic AEs are still not well-defined. Therefore, this study aimed to identify the association between pancreatic AEs and ICIs treatments and to characterize the main features of ICI-related pancreatic injury (ICIPI) based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Data from the first quarter of 2015 to the first quarter of 2021 in the database were extracted to conduct a disproportionality analysis. The selection of AEs related to the pancreas relied on previous studies and preferred terms from the Medical Dictionary for Regulatory Activities. Two main disproportionality analyses-the reporting odds ratio (ROR) and information component (IC)-were used to evaluate potential associations between ICIs and pancreatic AEs. RESULTS: In total, 2,364 cases of pancreatic AEs in response to ICIs were extracted from the FAERS database, of which, 647 were identified as ICI-associated pancreatitis and 1,293 were identified as ICI-associated diabetes mellitus. Generally, significant signals can be detected between pancreatic AEs and all ICIs treatments (ROR025 = 3.30, IC025 = 1.71). For monotherapy, the strongest signal associated with pancreatitis was reported for anti-PD-L1 (ROR025 = 1.75, IC025 = 0.76), whereas that with diabetes mellitus was reported for anti-PD-1 (ROR025 = 6.39, IC025 = 2.66). Compared with monotherapy, combination therapy showed stronger associations with both ICI-associated pancreatitis (ROR025 = 2.35, IC025 = 1.20 vs. ROR025 = 1.52, IC025 = 0.59) and ICI-associated diabetes mellitus (ROR025 = 9.53, IC025 = 3.23 vs. ROR025 = 5.63, IC025 = 2.48), but lower fatality proportion. CONCLUSIONS: ICIs were significantly associated with the over-reporting frequency of pancreatic AEs, in which combination therapy posed a higher reporting frequency. Therefore, patients should be informed of these potential toxicities before ICIs medications are administered.

5.
Expo Health ; : 1-2, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35474720
6.
Chemosphere ; 300: 134569, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35421440

RESUMO

Irrigation and fertilizer application can lead to significant changes in groundwater quality. In this study, a field irrigation experiment was carried out from April 9 to 23, 2021 under irrigation and fertigation conditions to understand the mechanisms of moisture movement, soil salt migration, and nitrogen transformation in the soil profile. Continuous in-situ monitoring and sampling of soil and irrigation water, as well as stable isotopes, chemical parameters, and soluble salt analyses, were performed in this research. The results showed that the time cost by the irrigation water in the vadose zone was about 5 h. The infiltrated irrigation water was accompanied by high concentrations of soluble salts, leached from the soil layers of 20-80 cm and 100-150 cm, which is associated with the leaching of Na+, Cl-, SO42-, and Ca2+ and the dissolution of minerals such as gypsum and halite. Furthermore, the variations in nitrogen concentrations (NH4+ and NO3-) in the soil profile suggested that fertilizer application was the main source of NO3- in the soil and groundwater, while irrigation was the biggest driving force for nitrogen transport and transformation in soil. The application of urea fertilizer can increase the content of ammonium nitrogen at the soil layer of 0-80 cm. This nitrogen form can be subsequently transformed to nitrate nitrogen during the water transport to the groundwater. The current study provides a strong scientific basis for the protection and management of groundwater and soil quality in agricultural areas.

7.
RSC Adv ; 12(14): 8394-8403, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35424792

RESUMO

Triazolium-based ionic liquids (T1, T2 and T3) with or without terminal hydroxyl groups were prepared via Cu(i) catalysed azide-alkyne click chemistry and their properties were investigated using various technologies. The hydroxyl groups obviously affected their physicochemical properties, where with a decrease in the number of hydroxyl groups, their stability and conductivity were enhanced. T1, T2 and T3 showed relatively high thermal stability, and their electrochemical stability windows (ESWs) were 4.76, 4.11 and 3.52 V, respectively. T1S-20 was obtained via the addition of zinc trifluoromethanesulfonic acid (Zn(CF3SO3)2) and lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) to T1, displaying conductivity and ESW values of 1.55 × 10-3 S cm-1 and 6.36 V at 30 °C, respectively. Subsequently, a Zn/Li3V2(PO4)3 battery was assembled using T1S-20 as the electrolyte and its performances at 30 °C and 80 °C were investigated. The battery showed a capacity of 81 mA h g-1 at 30 °C, and its capacity retention rate was 89% after 50 cycles. After increasing the temperature to 80 °C, its initial capacity increased to 111 mA h g-1 with a capacity retention rate of 93.6% after 100 cycles, which was much higher than that of the aqueous electrolyte (WS-20)-based zinc ion battery (71.8%). Simultaneously, the T1S-20 electrolyte-based battery exhibited a good charge/discharge efficiency, and its Coulomb efficiency was 99%. Consequently, the T1S-20 electrolyte displayed a better performance in the Zn/Li3V2(PO4)3 battery than that with the aqueous electrolyte, especially at high temperature.

8.
Ann Transl Med ; 10(6): 361, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35434013

RESUMO

Background: Breast cancer is the most common malignant tumor among all female tumors. It seriously affects the health and lives of patients, and poses a significant economic burden. The study of the molecular mechanisms of breast cancer occurrence, proliferation and growth and development is of great clinical significance. Methods: Notch1 knockout mice were obtained by gene targeting. The expression of inflammatory factor arginase-1 in each group of tumors was observed by immunofluorescence staining. Semi-quantitative detection of Notch1, Arginase-1, and proteins belonging to the PI3K-AKT pathway by western blot. The expression level of interleukin-3 (IL-3), and IL-4 in serum was quantified by enzyme linked immunosorbent assay (ELISA). Results: In this study, Notch1 knockout in mice promoted the cell proliferation of breast cancer. Further study on molecular mechanisms demonstrated that the increased cell proliferation resulted from the activation of the PI3K-AKT signal transduction pathway. In addition, the expression of the M2-type inflammatory factor arginase-1 significantly increased, which was dependent on the activation of the PI3K-AKT pathway, indicating that Notch1 knockout in mice promoted the polarization of tumor-associated macrophages (TAMs). Consistent with this, IL-3 and IL-4 expression also significantly increased in the serum of Notch1 knockout mice. Conclusions: According to our results, Notch1 knockout in mice significantly promoted the cell proliferation of breast cancer, not only by activating the PI3K-AKT pathway, but also by promoting the polarization of TAMs towards the M2-type phenotype.

10.
J Periodontol ; 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35460076

RESUMO

AIMS: Recent evidence suggests that periodontitis causes hypertension, which is a precursor to development of other systemic diseases. The aim of this study was to examine the effect of hypertension and periodontitis on the risk of subsequent systemic disease. MATERIALS AND METHODS: This longitudinal cohort study included 244,393 UK Biobank participants who were free of systemic disease other than hypertension at baseline. Self-reported responses of painful gums or loose teeth were surrogates for periodontitis. Hypertensives were identified by clinical diagnosis, or elevated blood pressure (> = 140/90 mmHg). Systemic diseases including cancer, cardiovascular disease and diabetes were identified from linked diagnostic codes. Multivariable Cox proportional hazard models were used to quantify the risk of systemic diseases and all-cause mortality, stratified by hypertensive and periodontitis status. RESULTS: The average age of the study population was 55.4 (standard deviation[SD:] 8.1) years, and 130,220 (53.3%) participants were female. At baseline, 131,566 (53.8%) participants were hypertensive and 4.5% reported periodontitis. The incidence rates of all systemic diseases were higher in hypertensive than non-hypertensive participants of the same periodontitis status. In hypertensives, an additive effect was observed for periodontitis on the risks of cardiovascular disease (adjusted hazard ratio[HR]: 1.35, 95% confidence interval[CI]: 1.21-1.53) and respiratory disease (HR: 1.11, 95% CI: 0.95-1.30) compared to hypertensive healthy controls. CONCLUSION(S): Hypertensives with periodontitis have exacerbated risks of several systemic diseases. Future interventional studies should consider the effect of periodontal treatment on systemic outcomes in targeted hypertensive populations. This article is protected by copyright. All rights reserved.

11.
Sci Rep ; 12(1): 4605, 2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35301368

RESUMO

Platelet ß3-integrin signaling through Talin is crucial in platelet transmembrane signaling, activation, adhesion, spreading and aggregation, and remains unclear in mechano-microenvironments. In order to examine Talin-ß3 integrin biophysical connectivity, a series of "ramp-clamp" steered molecular dynamics (SMD) simulations were performed on complex of F3 domain of Talin and cytoplasmic tail of ß3 integrin to imitate different force-loads in platelet. Pull-induced allostery of the hydrophobic pocket in F3 domain might markedly enhance complex rupture-force (> 150pN) and slow down breakage of the complex; the complex should mechano-stable for its conformational conservation under loads (≤ 80pN); increasing force below 60pN would decrease the complex dissociation probability, and force-induced extension of ß5 strand on Talin and binding site residues, ASP740 and ALA742 as well as Asn744, on ß3-integrin were responsible for the force-enhanced linkage of the Talin-ß3 integrin. Force might enhance biophysical connectivity of ß3-integrin signaling through Talin by a catch bond mechanism, which be mediated by the force-induced allostery of complex at clamped stage. This work provides a novel insight into the force-regulated transmembrane ß3-integrin signaling and its molecular basis for platelet activation, and exhibited a potential power of the present computer strategy in predicting mechanical regulation on ligand-receptor interaction under loads.


Assuntos
Integrina beta3 , Talina , Integrina beta1/metabolismo , Integrina beta3/metabolismo , Fenômenos Mecânicos , Simulação de Dinâmica Molecular , Ligação Proteica , Talina/metabolismo
12.
Chem Biodivers ; : e202101021, 2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35324082

RESUMO

A bis-dimethylamine substituted xanthone (Xan-2) was obtained by cationic modification of the free C3 and C6 hydroxy groups of 1,3,6-trihydroxyxanthone (Xan-1) which was isolated from Polygala hongkongensis Hemsl.. The results of the spectroscopic analysis, melting profiles, electrophoretic migration, PCR assay and molecular docking indicated that the hydrophobic plane of Xan-1 and Xan-2 could intercalate into the DNA base pairs meanwhile the basic amine alkyl chain of Xan-2 could bind with DNA phosphate framework via electrostatic interaction. Thus, Xan-2 exhibited higher DNA binding affinity than Xan-1. Further study showed that Xan-2 could inhibit the proliferation of HeLa, SGC-7901 and A549 cells effectively by MTT assay and induce apoptosis of HeLa cells as detected by AO/EB staining and flow cytometry assay. Interestingly, Xan-2 exhibited selective cytotoxicity to cells, which was proved by its relatively low inhibitory effect on Raw 264.7 cell. What these studies mean is that disubstituted amine alkyl chains will play an important role in DNA binding property and cytotoxic activity, providing a direction for the development of novel potential antitumor agents.

13.
Sci Rep ; 12(1): 4258, 2022 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-35277581

RESUMO

To compare the efficacy of internal limiting membrane (ILM) flap covering to that of ILM flap insertion for the treatment of macular hole retinal detachment (MHRD) in highly myopic eyes with axial length (AL) ≥ 30 mm. We retrospectively analysed the medical records of 48 MHRD patients with high myopia (AL ≥ 30 mm). According to different surgical methods, the patients were divided into a covering group (23 eyes) and an insertion group (25 eyes). The rate of retinal reattachment and MH closure were compared between the two groups, and the related factors affecting the initial anatomical results were analysed. After primary vitrectomy and single silicone oil removal, there were 18 eyes (78.3%) in the covering group, and 20 eyes (80.0%) in the insertion group had retinal reattachment (P = 1.000). Moreover, 16 eyes (69.6%) in the covering group and 17 eyes (68.0%) in the insertion group had their MHs sealed (P = 0.907). The best-corrected visual acuity (BCVA) at 12 months and the improvement in BCVA postoperatively in the two groups were not statistically significant (P = 0.543, 0.955). Logistic regression analysis showed that elongated AL (OR = 1.844, 95% CI 1.037-3.280, P = 0.037) and higher choroidal atrophy (OR = 2.986, 95% CI 1.011-8.821, P = 0.048) were risk factors affecting initial anatomical success. For extremely high-myopia MHRD with AL ≥ 30 mm, ILM flap covering and insertion can both effectively seal the MH and promote retinal reattachment, but the visual function improvement may still be limited. The longer the AL and the higher the choroidal atrophy, the greater is the risk of initial anatomical failure.


Assuntos
Miopia , Descolamento Retiniano , Perfurações Retinianas , Atrofia/complicações , Membrana Basal , Humanos , Miopia/complicações , Descolamento Retiniano/etiologia , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Vitrectomia/métodos
14.
Eur J Med Chem ; 233: 114216, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35227980

RESUMO

With the aging of the population intensifying, finding a cure or reasonable treatment for Alzheimer' disease (AD) has become an urgent priority. To target the multi-facets of AD, a class of chrysin derivatives (1-4) were rationally designed and synthesized by the multi-target-directed ligands (MTDLs) strategy, which were characterized by 1H NMR, 13C NMR, MS and elemental analysis. 1-4 showed inhibitory activities on reactive oxygen species, Aß1-42 aggregation (self-, Cu2+-induced, AChE-induced). They were also potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with selectivity toward BuChE. Compound 1 as the most promising candidate exhibited the highest selective BuChE inhibition (SI = 15). Furthermore, the kinetic study suggested compound 1 to be a mixed type inhibitor. The results of docking study were consistent with the in vitro results. In addition, compound 1-4 showed favorable blood-brain barrier (BBB) penetration and drug-like property in silico prediction. The corresponding copper complexes of 1-4 have also been synthesized. 1-4 selectively chelated Cu2+, Fe2+, Zn2+ and Al3+ ions, while had no chelating ability to other biometals. The copper complexes also showed good AChE, BuChE and reactive oxygen species inhibitory activities. Notably, the single crystals of 1-Cu(II) complex [Cu(C19H18NO4)2] were prepared for the first time and characterized by X-ray single crystal diffraction. X-ray crystallography analysis of 1-Cu(II) complex provided a reliable structure-activity insight at the molecular level about the antioxidative and Aß1-42 disaggregation activities. Compound 1 might be a good lead compound to develop promising candidate analogs as AD therapeutics.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Acetilcolinesterase , Peptídeos beta-Amiloides , Butirilcolinesterase , Cristalografia por Raios X , Desenho de Fármacos , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
15.
Biology (Basel) ; 11(3)2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35336819

RESUMO

Tceal7 has been identified as a direct, downstream target gene of MRF in the skeletal muscle. The overexpression of Tceal7 represses myogenic proliferation and promotes cell differentiation. Previous studies have defined the 0.7 kb upstream fragment of the Tceal7 gene. In the present study, we have further determined two clusters of transcription factor-binding motifs in the 0.7 kb promoter: CRE#2-E#1-CRE#1 in the proximal region and Mef2#3-CRE#3-E#4 in the distal region. Utilizing transcription assays, we have also shown that the reporter containing the Mef2#3-CRE#3-E#4 motifs is synergistically transactivated by Mef2c and Creb1. Further studies have mapped out the protein-protein interaction between Mef2c and Creb1. In summary, our present studies support the notion that the triple complex of Mef2c, Creb1 and Myod interacts with the Mef2#3-CRE#3-E#4 motifs in the distal region of the Tceal7 promoter, thereby driving Tceal7 expression during skeletal muscle development and regeneration.

16.
Mitochondrial DNA B Resour ; 7(3): 456-457, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35274042

RESUMO

Trigonotis peduncularis (Boraginaceae) is an annual or biannual herb widely distributed in temperate Asia and East Europe. The complete chloroplast genome of T. peduncularis was sequenced by high-throughput technologies and assembled for the first time. The complete chloroplast genome of T. peduncularis was 147,508 bp in length with a GC content of 37.6%, which includes a large single-copy region (80,546 bp), a pair of inverted repeats (24,877 bp), and a small single copy (17,208 bp). GC content of IR regions (43.3%) were higher than LSC (35.5%) and SSC (31.1%) regions. The genome was predicted to encode 130 genes, of which 114 were unique, including 80 protein-coding genes, 30 tRNA genes, and four rRNA genes. Result from phylogenetic analysis showed that T. peduncularis was sister to Plagiobothrys nothofulvus, and the intergeneric relationships among the six genera sampled in Boraginaceae were well resolved and strongly supported.

17.
Europace ; 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35244709

RESUMO

AIMS: People with atrial fibrillation (AF) frequently live with frailty, which increases the risk of mortality and stroke. This study reports the association between oral anticoagulation (OAC) and outcomes for people with frailty, and whether there is overall net benefit from treatment in people with AF. METHODS AND RESULTS: Retrospective open cohort electronic records study. Frailty was identified using the electronic frailty index. Primary care electronic health records of 89 996 adults with AF and CHA2DS2-Vasc score of ≥2 were linked with secondary care and mortality data in the Clinical Practice Research Database (CPRD) from 1 January 1998 to 30 November 2018. The primary outcome was a composite of death, stroke, systemic embolism, or major bleeding. Secondary outcomes were stroke, major bleeding, all-cause mortality, transient ischaemic attack, and falls. Of 89 996 participants, 71 256 (79.2%) were living with frailty. The prescription of OAC increased with degree of frailty. For patients not prescribed OAC, rates of the primary outcome increased alongside frailty category. Prescription of OAC was associated with a reduction in the primary outcome for each frailty category [adjusted hazard ratio, 95% confidence interval, no OAC as reference; fit: vitamin K antagonist (VKA) 0.69, 0.64-0.75, direct oral anticoagulant (DOAC) 0.42, 0.33-0.53; mild frailty: VKA 0.52, 0.50-0.54, DOAC 0.57, 0.52-0.63; moderate: VKA 0.54, 0.52-0.56, DOAC 0.57, 0.52-0.63; severe: VKA 0.48, 0.45-0.51, DOAC 0.58, 0.52-0.65], with cumulative incidence function effects greater for DOAC than VKA. CONCLUSION: Frailty among people with AF is common. The OAC was associated with a reduction in the primary endpoint across all degrees of frailty.

18.
Int J Gen Med ; 15: 1413-1427, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185344

RESUMO

PURPOSE: We aimed to characterize the expression patterns of glycolysis and hypoxia genes in colon cancers as well as their value in prognosis and immune microenvironment. METHODS: The expression profiles were acquired from the Cancer Genome Atlas database. Enrichment of hypoxia and glycolysis gene sets in colon cancer was identified by gene set enrichment analysis. Then, a prognostic signature was built up after Cox regression analyses, and overall survival analysis validated the predictive ability. Immune status and infiltration in cancer tissues were explored using the single sample gene set enrichment analysis and CIBERSORT algorithm. A nomogram model integrating clinical variables and the gene signature was established and assessed. RESULTS: Altogether, 378 cancer and 39 control cases were enrolled. Three glycolysis gene sets and two hypoxia gene sets were enriched in colon cancer (P < 0.05). Five independent genes (ENO3, GPC1, P4HA1, SPAG4, and STC2) were significantly correlated with prognosis of colon cancer patients. Patients with higher risks had significantly better prognosis than those with lower risks (P = 0.002 and AUC = 0.750), which was also observed in the elderly, female and stage I-II subgroups (P < 0.05). In high-risk cases, proportion of NK cells resting increased (P < 0.05) while that of dendritic cells activated (P < 0.05), dendritic cells resting (P < 0.01) and monocytes (P < 0.01) decreased. Besides, expressions of 22 checkpoint genes were found abnormal in groups with different risks (P < 0.05). The predictive nomogram presented satisfactory performance with C-index of 0.771 (0.712-0.830). The area under ROC curve was 0.796 and 0.803 for 3- and 5-year survival prediction, respectively. CONCLUSION: A glycolysis and hypoxia combined gene signature was a promising method to evaluate the prognosis and immune infiltration of colon cancer patients, which may provide a new tool for cancer management.

19.
Materials (Basel) ; 15(4)2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35207826

RESUMO

Magnesium matrix composites are considered a desired solution for lightweight applications. As an attractive thermal management material, diamond particle-reinforced Mg matrix (Mg/diamond) composites generally exhibit thermal conductivities lower than expected. To exploit the potential of heat conduction, a combination of Cr coating on diamond particles and squeeze casting was used to prepare Mg/diamond (Cr) composites. The thickness of the Cr coating under different coating processes (950 °C/30 min, 950 °C/60 min, 950 °C/90 min, 1000 °C/30 min, and 1050 °C/30 min) was measured by FIB-SEM to be 1.09-2.95 µm. The thermal conductivity (TC) of the Mg/diamond composites firstly increased and then decreased, while the coefficient of thermal expansion (CTE) of Mg/diamond (Cr) composite firstly decreased and then increased with the increase in Cr coating thickness. The composite exhibited the maximum TC of 202.42 W/(m·K) with a 1.20 µm Cr coating layer, while a minimum CTE of 5.82 × 10-6/K was recorded with a coating thickness of 2.50 µm. The results clearly manifest the effect of Cr layer thickness on the TC and CTE of Mg/diamond composites.

20.
Bioact Mater ; 13: 179-190, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35224300

RESUMO

Beyond traditional endothelium-dependent vessel (EDV), vascular mimicry (VM) is another critical tumor angiogenesis that further forms in many malignant metastatic tumors. However, the existing anti-angiogenesis combined chemotherapeutics strategies are only efficient for the treatment of EDV-based subcutaneous tumors, but remain a great challenge for the treatment of in situ malignant metastatic tumor associated with EDV and VM. Here, we demonstrate a self-assembled nanoparticle (VE-DDP-Pro) featuring self-anti-EDV and -VM capacity enables to significantly enhance the treatment efficacy of cisplatin (DDP) against the growth and metastasis of ovarian cancer. The VE-DDP-Pro is constructed by patching DDP loaded cRGD-folate-heparin nanoparticles (VE) onto the surface of protamine (Pro) nanoparticle. We demonstrated the self-anti-angiogenesis capacity of VE-DDP-Pro was attributed to VE, which could significantly inhibit the formation of EDV and VM by regulating signaling pathway of MMP-2/VEGF, AKT/mTOR/MMP-2/Laminin and AKT/mTOR/EMT, facilitating chemotherapeutics to effectively suppress the development and metastasis of ovarian cancer. Thus, combing with the chemotherapeutics effectiveness of DDP, the VE-DDP-Pro can significantly enhance treatment efficacy and prolong median survival of mice with metastatic ovarian cancer. We believe our self-assembled nanoparticles integrating the anti-EDV and anti-VM capacity provide a new preclinical sight to enhance the efficacy of chemotherapeutics for the treatment malignant metastasis tumor.

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