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1.
Front Immunol ; 13: 975676, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110842

RESUMO

Novel therapeutics against the global threat of multidrug-resistant Neisseria gonorrhoeae are urgently needed. Gonococci evade killing by complement by binding factor H (FH), a key inhibitor of the alternative pathway. FH comprises 20 short consensus repeat (SCR) domains organized as a single chain. Gonococci bind FH through domains 6 and 7, and C-terminal domains 18 through 20. Previously, we showed that a chimeric protein comprising (from the N- to C-terminus) FH domains 18-20 (containing a point mutation in domain 19 to prevent lysis of host cells) fused to human IgG1 Fc (called FH*/Fc1) killed gonococci in a complement-dependent manner and reduced the duration and bacterial burden in the mouse vaginal colonization model of gonorrhea. Considering the N. gonorrhoeae-binding FH domains 18-20 are C-terminal in native FH, we reasoned that positioning Fc N-terminal to FH* (Fc1/FH*) would improve binding and bactericidal activity. Although both molecules bound gonococci similarly, Fc1/FH* displayed a 5-fold lower IC50 (the concentration required for 50% killing in complement-dependent bactericidal assays) than FH*/Fc1. To further increase complement activation, we replaced human IgG1 Fc in Fc1/FH* with Fc from human IgG3, the most potent complement-activating IgG subclass, to obtain Fc3/FH*. Bactericidal activity was further increased ~2.3-fold in Fc3/FH* compared to Fc1/FH*. Fc3/FH* killed (defined by <50% survival) 45/45 (100%) diverse PorB1B-expessing gonococci, but only 2/15 PorB1A-expressing isolates, in a complement-dependent manner. Decreased Fc3/FH* binding accounted for the limited activity against PorB1A strains. Fc3/FH* was efficacious against all four tested PorB1B gonococcal strains in the mouse vaginal colonization model when administered at a dose of 5 µg intravaginally, daily. Furthermore, Fc3/FH* retained bactericidal activity when reconstituted following lyophilization or spray-drying, suggesting feasibility for formulation into intravaginal rings. In conclusion, Fc3/FH* represents a promising prophylactic immunotherapeutic against multidrug-resistant gonococci.


Assuntos
Gonorreia , Neisseria gonorrhoeae , Animais , Fator H do Complemento/metabolismo , Proteínas do Sistema Complemento/metabolismo , Modelos Animais de Doenças , Feminino , Gonorreia/tratamento farmacológico , Humanos , Imunoglobulina G/metabolismo , Camundongos , Neisseria gonorrhoeae/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/farmacologia
2.
World J Clin Cases ; 10(20): 6794-6802, 2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-36051138

RESUMO

BACKGROUND: Transurethral columnar balloon dilatation of the prostate (TUCBDP) is a new surgical treatment, but its efficacy remains controversial because of limited clinical application. AIM: To investigate the clinical effect of TUCBDP for benign prostatic hyperplasia (BPH). METHODS: Overall, 140 patients with BPH who underwent surgical treatment were included in the study. A random number table was used to divide the participants into study and control groups (n = 70 per group). The study group underwent TUCBDP. The prostate resection surgical time, intraoperative blood loss, bladder irrigation time, catheter indwelling time, length of hospital stay, International Prostate Symptom Score (IPSS), maximum urine flow rate (Qmax), residual urine volume (RUV), changes in the International Erectile Function Score (IIEF-5) score, serum prostate-specific antigen (PSA), quality of life (QOL) score, and surgical complications were compared in both groups. RESULTS: The operation time, intraoperative blood loss volume, bladder flushing time, urinary catheter indwelling time, and length of hospital stay were significantly lower in the study group than in the control group (P < 0.05). There were no significant differences in the IPSS, Qmax, and RUV measurements between the study and control groups (P > 0.05). However, at 3 mo post-surgery, the IPSS and RUV measurements were both lower (P < 0.05) and Qmax values were higher (P < 0.05) compared to the pre-surgery results in both groups. The IIEF-5 scores before and 3 mo after surgery were not significantly different between the study and control groups (P > 0.05). At 1 mo after surgery, the IIEF-5 score was higher in the study group than in the control group (P < 0.05). The serum PSA levels and QOL scores before treatment and at 1 and 3 mo after treatment were not significantly different between the study and control groups (P > 0.05). However, lower serum PSA levels and QOL scores were observed after 1 and 3 mo of treatment compared to pre-treatment levels in the study group (P < 0.05). The surgical complication rate of the study group (4.29%) was lower than that of the control group (12.86%; P < 0.05). CONCLUSION: TUCBDP for BPH and transurethral resection of the prostate can achieve better results, but the former method is associated with less surgical trauma.

3.
J Pathol ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098222

RESUMO

Multifocal esophageal squamous cell carcinomas (ESCCs) can be diagnosed as of multicentric origin (MO) or intramural metastasis (IMM). We aimed here to accurately discriminate MO from IMM and explore the tumor immune microenvironment of multifocal ESCCs. Multifocal ESCCs were identified in 333 ESCC patients, and in 145 patients discrimination between MO and IMM was not possible by histopathological examination. Of the 145 patients, tissues of 14 were analyzed by whole-exome sequencing (WES) of 71 different tumor regions, and MO, IMM, and MO/IMM mixed groups were identified in 3, 10 and 1 cases, respectively, based on the similarity of genomic architecture between or among different tumors from one patient. Further phylogenetic analyses revealed complex clonal evolution patterns in IMM cases, and tumor cells disseminated from the primary tumors to IMM tumors were independent of lymph node metastasis. The NanoString-based assay showed that immune cell infiltrates were significantly enriched, and the immune and proliferation pathways were more activated, in large tumors than small ones in MO but not IMM cases. Similarly, PD-L1 expression and the density of paratumoral CD8+ T cells were higher in large tumors than in small tumors in MO. Taken together, through analysis of the genomic and immune landscapes, our study has comprehensively characterized the heterogeneity and clonal relationship of multifocal ESCCs, which may be helpful for distinguishing MO from IMM, and for interpreting the immunotherapy responses for multifocal ESCC patients. This article is protected by copyright. All rights reserved.

4.
Front Pharmacol ; 13: 950719, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052139

RESUMO

Purpose: This study compared the effect of indobufen with that of aspirin on platelet function in patients with stable coronary heart disease after percutaneous coronary intervention (PCI). Methods: Patients with stable coronary heart disease who had undergone PCI and received dual antiplatelet therapy (aspirin 100 mg + clopidogrel 75 mg once daily) for at least 12 months were allocated to receive indobufen 100 mg twice daily + clopidogrel 75 mg once daily, clopidogrel 75 mg once daily alone, indobufen 100 mg twice daily alone, and aspirin 100 mg once daily alone for 1 month each in an open-label crossover manner. Platelet function was assessed by using the rates of arachidonic acid (AA)-induced platelet aggregation (AA-PAR) and adenosine diphosphate (ADP)-induced platelet aggregation (ADP-PAR) measured by light transmission aggregometry, the platelet reactivity index measured by vasodilator-stimulated phosphoprotein (PRI-VASP), and the plasma and urinary thromboxane B2 (TXB2) concentrations recorded at baseline and during each treatment phase. Results: Of 56 patients enrolled, 52 completed the study. The AA-PAR was lower in the indobufen alone group than in the aspirin alone group [5.21% (3.39, 7.98) vs. 5.27% (4.06, 6.60), p = 0.038], while biologically, a difference of 0.06% may represent no significant difference; there was no significant between-group difference in the plasma [531.16 pg/ml (203.89, 1035.06) vs. 373.93 pg/ml (194.04, 681.71), p = 0.251] or urinary [3951.97 pg/ml (2006.95, 6077.01) vs. 3610.48 pg/ml (1664.60, 6247.61), p = 0.717] TXB2 concentration. When the aspirin + clopidogrel group and indobufen + clopidogrel group were compared, similar results were found for AA-PAR [3.97% (3.05, 5.12) vs. 3.83% (3.10, 5.59), p = 0.947] and both plasma [849.47 pg/ml (335.96, 1634.54) vs. 455.41 pg/ml (212.47, 1489.60), p = 0.629], and urinary [4122.97 pg/ml (2044.96, 7459.86) vs. 3812.81 pg/ml (1358.95, 6021.07), p = 0.165] TXB2 concentrations. ADP-PAR was lower in the clopidogrel alone group than in the indobufen alone group (47.04% ± 16.89 vs. 61.7% ± 10.50, p < 0.001), as was PRI-VASP (66.53% ± 18.06 vs. 77.72% ± 19.87, p = 0.002). Conclusion: These findings suggest that indobufen has antiplatelet effects similar to those of aspirin in patients with stable coronary heart disease after PCI, and may be an alternative for patients with aspirin intolerance after coronary stenting.

5.
ACS Omega ; 7(34): 29612-29624, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36061721

RESUMO

Different viewpoints on the oil-source correlation of the Angdarco paleo-reservoir in the Qiangtang Basin, northern Tibet, China, have seriously affected oil and gas exploration in this area. In this work, based on the results of biomarker analysis on six oil seepage samples and 11 potential source rock samples, the oil source of the oil seepages in the Angdarco area was examined by correlating the composition characteristics of n-alkanes, multiple factors of biomarkers, correlograms of biomarker parameters, and δ13C values of individual n-alkanes between oil seepages and potential source rocks. In addition, the sedimentary environment and thermal maturity characteristics of the potential source rocks were also discussed. The biomarkers indicated that the potential source rocks of the Lower Jurassic Quse Formation (J1q) presented characteristics of littoral sediments, deposited under suboxic conditions, while the potential source rocks of the Middle Jurassic Buqu Formation (J2b) were deposited in a marine sedimentary environment and presented characteristics of a low mature to mature stage. The potential source rocks of the Middle Jurassic Xiali Formation (J2x) were deposited in a low-salinity environment and presented characteristics of low-mature source rocks. Finally, the oil seepages of the Buqu Formation were deposited in a suboxic littoral environment and presented characteristics of a low mature to mature stage. It is concluded that the oil seepages in the Angdarco paleo-reservoir were mainly sourced from the Lower-Jurassic Quse oil shales. This work provides a scientific basis for the exploration of paleo-reservoirs in the southern Qiangtang Basin.

6.
Front Microbiol ; 13: 933882, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081794

RESUMO

For decades, lignocellulosic biomass has been introduced to the public as the most important raw material for the environmentally and economically sustainable production of high-valued bioproducts by microorganisms. However, due to the strong recalcitrant structure, the lignocellulosic materials have major limitations to obtain fermentable sugars for transformation into value-added products, e.g., bioethanol, biobutanol, biohydrogen, etc. In this review, we analyzed the recent trends in bioenergy production from pretreated lignocellulose, with special attention to the new strategies for overcoming pretreatment barriers. In addition, persistent challenges in developing for low-cost advanced processing technologies are also pointed out, illustrating new approaches to addressing the global energy crisis and climate change caused by the use of fossil fuels. The insights given in this study will enable a better understanding of current processes and facilitate further development on lignocellulosic bioenergy production.

8.
Materials (Basel) ; 15(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36079348

RESUMO

Using the heavy rare earth Dy element to improve coercivity is the most common solution for hindering the reduction in magnetic properties in the Nd-Fe-B magnet, and the effective utilization of Dy has become the focus of research in industrial society. In this work, we investigated the influence of DyHx addition and diffusion methods on the microstructure, magnetic performance, and thermal stability of the Nd-Y-Fe-B magnet with a Y-rich core structure. The coercivity of the DyHx addition magnet increases from 9.45 kOe to 15.51 kOe when adding 1.6 wt.% DyHx, while the DyHx diffusion magnet increases to 15.15 kOe. According to the analysis of the microstructure and elemental distribution, both Dy-rich shells were basically formed due to the diffusion process of Dy atoms. The Dy-rich shell in the DyHx addition magnet was similar with the original core-shell structure in the Nd-Y-Fe-B magnet. However, the distinct dual-shell structure consisting of a thinner Dy-rich shell and a Y-lean shell was constructed in the DyHx diffused magnet, contributing to the superior coercivity increment and Dy utilization efficiency. Furthermore, the remanence of the DyHx diffused magnet is up to 12.90 kG, which is better than that of the DyHx addition magnet (12.59 kG), due to fewer Dy atoms entering the 2:14:1 matrix grain to cause the antiferromagnetic coupling with Fe atoms. Additionally, the thermal stability of the DyHx diffusion magnet is also better than that of the DyHx addition magnet, owing to the elevated coercivity at room temperature, which expands the application range of the Nd-Y-Fe-B magnet to a certain extent.

9.
Front Surg ; 9: 962425, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061063

RESUMO

Objectives: The contributing factors for spondylitis after percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) remain unclear. Here, we sought to investigate the factors affecting spondylitis occurrence after PVP/PKP. We also compared the clinical characteristics between patients with tuberculous spondylitis (TS) and nontuberculous spondylitis (NTS) following vertebral augmentation. Methods: Literature searches (from January 1, 1982 to October 16, 2020) using MEDLINE, EMBASE, Google Scholar and Web of science databases were conducted to identify eligible studies according to predefined criteria. The local database was also retrospectively reviewed to include additional TS and NTS patients at our center. Results: Thirty studies from the literature and 11 patients from our local institute were identified, yielding a total of 23 TS patients and 50 NTS patients for analysis. Compared with NTS group, patients in the TS group were more likely to have a history of trauma before PVP/PKP treatment. Univariate analyses of risk factors revealed pulmonary tuberculosis and diabetes were significant factors for TS after PVP/PKP. Analyzing NTS, we found obesity, a history of preoperative trauma, urinary tract infection, diabetes and multiple surgical segments (≥2) were significantly associated with its occurrence following PVP/PKP treatment. Multivariate logistic analyses showed a history of pulmonary tuberculosis and diabetes were independent risk factors for TS after PVP/PKP, while diabetes and the number of surgically treated segments independently influenced NTS development. Conclusions: A history of pulmonary tuberculosis and diabetes were independent risk factors for TS. For NTS, diabetes and the number of surgically treated segments significantly influenced the occurrence of postoperative spinal infection. These data may be helpful for guiding risk stratification and preoperative prevention for patients, thereby reducing the incidence of vertebral osteomyelitis after PVP/PKP.

10.
Front Cardiovasc Med ; 9: 903390, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110413

RESUMO

Background: Remnant lipoprotein cholesterol (RC) is an independent risk factor for cardiovascular disease (CVD). However, the relationships of remnant cholesterol and other conventional lipid parameters with new-onset carotid plaque are not fully understood in the Chinese community-based population. Materials and methods: A total of 872 plaque-free participants (51.39 ± 4.96 years old) with no history of CVD were included in this study. The plasma concentrations of RC were calculated by subtracting low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) from total cholesterol (TC). Multivariate regression models were used to evaluate and compare the associations between RC and other lipid parameters and new-onset carotid plaque. Results: After a mean 6.77-year follow-up, the incidence of new-onset carotid plaque was 188 (21.56%). RC was significantly associated with new-onset carotid plaque [Odd ratio (OR) = 1.57 per 1 mmol/L increase, 95% confidence interval (CI): 1.03-2.41, p = 0.038]. The highest tertile of RC (T3 group) had the highest risk of new-onset carotid plaque (OR = 2.53, 95% CI: 1.63-3.95). Similar results were seen for increased other lipid parameters, but decreased HDL-C levels. When adding another lipid parameter into the adjusted model with RC simultaneously, only RC remained significantly associated with new-onset carotid plaque after adjusting for other lipid parameters (all p value < 0.005). Furthermore, RC was strongly associated with new-onset carotid plaque in participants with lower baseline LDL-C levels. Conclusion: Increased RC levels were superior to other conventional lipid parameters to be associated with new-onset carotid plaque in the Chinese community-based population. Furthermore, RC should be considered in participants with lower LDL-C levels for the purpose of early atherosclerosis prevention.

11.
Phytomedicine ; 106: 154405, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36067659

RESUMO

BACKGROUND: Stent implantation has been increasingly applied for the treatment of obstructive coronary artery disease, which, albeit effective, often harasses patients by in-stent restenosis (ISR). PURPOSE: The present study was to explore the role of compound Chinese medicine Cardiotonic Pills® (CP) in attenuating ISR-evoked myocardial injury and fibrosis. STUDY DESIGN: Chinese miniature pigs were used to establish ISR model by implanting obsolete degradable stents into coronary arteries. Quantitative coronary angiography (QCA) was performed to confirm the success of the model. METHODS: CP was given at 0.2 g/kg daily for 30 days after ISR. On day 30 and 60 after stent implantation, the myocardial infarct and myocardial blood flow (MBF) were assessed. Myocardial histology was evaluated by hematoxylin-eosin and Masson's trichrome staining. The content of ATP, MPO, and the activity of mitochondrial respiratory chain complex Ⅳ were determined by ELISA. Western blot was performed to assess the expression of ATP5D and related signaling proteins, and the mediators of myocardial fibrosis. RESULTS: Treatment with CP diminished myocardial infarct size, retained myocardium structure, attenuated myocardial fibrosis, and restored MBF. CP ameliorated energy metabolism disorder, attenuated TGFß1 up-regulation and reversed its downstream gene expression, such as Smad6 and Smad7, and inhibited the increased expression of MCP-1, PR S19, MMP-2 and MMP-9. CONCLUSION: CP effectively protects myocardial structure and function from ISR challenge, possibly by regulating energy metabolism via inactivation of RhoA/ROCK signaling pathway and inhibition of monocyte chemotaxis and TGF ß1/Smads signaling pathway.

12.
Biomed Res Int ; 2022: 3008842, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046463

RESUMO

Background: Kangai injection is a traditional Chinese medicine (TCM) mixed by extracts from astragalus, ginseng, and kurorinone with modern technology. It is a commonly used antitumor injection in China, but the mechanism of Kangai injection in the treatment of colorectal cancer (CRC) is still unclear. The purpose of this study is to explore the mechanism of Kangai injection against CRC using network pharmacology and molecular docking technology. Methods: Targets of Kangai injection in CRC were predicted by SwissTargetPrediction and DisGeNET databases. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed by using the DAVID database. A component-disease-target gene-pathway network was constructed by Cytoscape 3.8.0 software. Results: 114 overlapping targets of Kangai injection and CRC were used to construct a PPI network, and the top 10 hub targets of Kangai injection were rated from high to low as TP53, VEGFA, EGFR, TNF, ESR1, STAT3, HSP90AA1, HDAC1, AR, and MMP9. The ingredient-target-disease interactive network was constructed, which included 22 compounds and 114 overlapping targets with 161 nodes and 707 edges. Entries of enrichment analysis were obtained based on P value (<0.05), which included 19 of GO-MF, 217 of GO-BP, 8 of GO-CC, and 13 KEGG. Molecular docking analysis showed that Kangai injection strongly interacted with top 10 hub target proteins. Conclusion: Network pharmacology intuitively showed the multicomponent, multiple targets, and multiple pathways of Kangai injection in the treatment of CRC. The molecular docking experiment verified that compounds of Kangai injection had good binding ability with top 10 hub target proteins as well.


Assuntos
Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede , Mapas de Interação de Proteínas/genética
13.
Cancer Sci ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047973

RESUMO

Small cell lung cancer (SCLC) is the most devastating subtype of lung cancer with no clinically available prognostic biomarkers. N6 -methyladenosine (m6 A) and noncoding RNAs play critical roles in cancer development and treatment response. However, little is known about m6 A-related long noncoding RNAs (lncRNAs) in SCLC. We used 206 limited-stage SCLC (LS-SCLC) samples from two cohorts to undertake the first and most comprehensive exploration of the m6 A-related lncRNA profile in SCLC and constructed a relevant prognostic signature. In total, 289 m6 A-related lncRNAs were screened out. We then built a seven-lncRNA-based signature in the training cohort with 48 RNA sequencing data using univariate and multivariate Cox regression models. The signature was well validated in an independent cohort containing 158 cases with quantitative PCR data. In both cohorts, the signature divided patients into high- and low-risk groups with significantly different survival rates (both p < 0.001). Our signature predicted chemotherapy survival benefit in patients with LS-SCLC. Receiver operating characteristic and C-index analyses indicated that the signature was better at predicting prognosis and chemotherapy benefit than other clinicopathologic features. Moreover, the signature was identified as an independent predictor of prognosis and chemotherapy response in different cohorts. Furthermore, functional analysis showed that multiple activated immune-related pathways were enriched in the low-risk group. Additionally, the signature was also closely related to various immune checkpoints and inflammatory responses. We generated the first clinically available m6 A-related lncRNA signature to predict prognosis and chemotherapy benefit in patients with LS-SCLC. Our findings could help optimize the clinical management of patients with LS-SCLC and inform future therapeutic targets for SCLC.

14.
Nat Commun ; 13(1): 5061, 2022 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-36030262

RESUMO

Climate change mitigation measures can yield substantial air quality improvements while emerging clean air measures in developing countries can also lead to CO2 emission mitigation co-benefits by affecting the local energy system. Here, we evaluate the effect of China's stringent clean air actions on its energy use and CO2 emissions from 2013-2020. We find that widespread phase-out and upgrades of outdated, polluting, and inefficient combustion facilities during clean air actions have promoted the transformation of the country's energy system. The co-benefits of China's clean air measures far outweigh the additional CO2 emissions of end-of-pipe devices, realizing a net accumulative reduction of 2.43 Gt CO2 from 2013-2020, exceeding the accumulated CO2 emission increase in China (2.03 Gt CO2) during the same period. Our study indicates that China's efforts to tackle air pollution induce considerable climate benefit, and measures with remarkable CO2 reduction co-benefits deserve further attention in future policy design.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Dióxido de Carbono , China , Mudança Climática
15.
Food Funct ; 13(18): 9243-9253, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36000543

RESUMO

As a type of phytoestrogen, lignans have attracted attention in recent years for their nutritional functions. To investigate the effects of lignans on the structural and nutritional functions of starch, honokiol (HK) and arctiin (AC) were complexed with rice starch respectively under high-pressure homogenization (UHPH) (UHPHRS/HK and UHPHRS/AC). The results showed that both HK and AC could form inclusive complexes with rice starch via non-covalent bonding (hydrophobic interaction and hydrogen bonds), and these complexes could further form V-type crystals and aggregates, which reduced the starch digestibility as well as endowing them with the ability to retard glucose release and bind sodium cholate. Interestingly, due to its smaller molecular size, HK could induce starch to form a more compact structure than AC, leading to better nutritional functions. When the addition of HK/AC reached 8%, the resistant starch content could reach 26% and 19.8%, respectively. Meanwhile, the glucose dialysis retardation index could increase to 17.2% and 14.8%, respectively, and the sodium cholate-binding capacity could increase to 33.1 mg g-1 and 21.8 mg g-1, respectively. These results demonstrated that UHPH with lignans' molecular interaction could be beneficial for controlling the nutritional functions of starch products with the desired digestibility.


Assuntos
Lignanas , Oryza , Compostos Alílicos , Compostos de Bifenilo , Glucose/metabolismo , Lignanas/metabolismo , Oryza/química , Fenóis , Fitoestrógenos/metabolismo , Amido Resistente , Colato de Sódio , Amido/química
16.
Front Cardiovasc Med ; 9: 938519, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935636

RESUMO

Objectives: Using quantitative coronary angiography (QCA), optical coherence tomography (OCT), histomorphometry, and pharmacokinetics, this study tried to evaluate the safety and efficacy of Biomagic rapamycin-eluting bioabsorbable scaffold (BVS) in non-atherosclerotic porcine coronary arteries. Background: Biomagic BVS is a new generation of thin-strut bioabsorbable scaffold. We conducted comparative study detailing pathological response, safety and efficacy of Biomagic BVS and the Firebird2 rapamycin-eluting cobalt-based alloy stent (DES) in a porcine coronary artery model. The animals were followed up at 14 days, 1, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months after stent implantation. Methods: A total of 143 devices (95 Biomagic and 48 Firebird2) were implanted in 2 or 3 main coronary arteries of 76 nonatherosclerotic swine and examined by QCA, OCT, light microscopy, and pharmacokinetics analyses at various time points. Results: Vascular responses to Biomagic and Firebird2 were largely comparable at all time points, with struts being sequestered within the neointima. The degree of inflammation of both devices was mild to moderate, although the Biomagic score was higher at 14 days to 24 months. However, there was no statistical difference between the two groups except 14 days. At each follow-up time point, the percentage of area stenosis in the Biomagic group was greater than that in the Firebird 2 group, but there was no statistical difference between the two groups at 3 and 12 months. The extent of fibrin deposition was similar between Biomagic and Firebird2, which peaked at 1 month and decreased rapidly thereafter. Pharmacokinetic study showed that coronary tissue sirolimus concentration remained above 2 ng/mg of tissue at 28 day. Histomorphometry showed expansile remodeling of Biomagic-implanted arteries starting after 12 months, and lumen area was significantly greater in Biomagic than Firebird2 at 36 and 42 months. These changes correlated with dismantling of Biomagic seen after 12 months. OCT images confirmed that degradation of Biomagic was complete by 36 months. Conclusions: Biomagic demonstrates comparable long-term safety to Firebird2 in porcine coronary arteries with mild to moderate inflammation. Although Biomagic was associated with greater percent stenosis relative to Firebird2 within 36 months, expansile remodeling was observed after 12 months in Biomagic with significantly greater lumen area at ≥36 months. Scaffold resorption is considered complete at 36 months.

17.
J Math Biol ; 85(2): 18, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35917035

RESUMO

Assuming that there are multiple batches of sterile males reared and released during the maturation period, we derive a switching delay differential model to study the fate of wild females under an impulsive and periodic release of sterile males. For the release magnitude of each batch c, we find two threshold values [Formula: see text] and [Formula: see text], and prove that when [Formula: see text], the model admits exactly two periodic solutions, among which one is asymptotically stable and the other is unstable. The trivial equilibrium, corresponding to the elimination of wild females, is locally asymptotically stable, and it becomes globally asymptotically stable when [Formula: see text]. One key step is to prove that every solution is sandwiched between two "good" solutions.


Assuntos
Culicidae , Animais , Simulação por Computador , Feminino , Masculino , Modelos Biológicos , Dinâmica Populacional
18.
Inorg Chem ; 61(35): 13678-13684, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36007887

RESUMO

Porous organic polymer (POP) coated on a metal-organic framework (MOF) has the functions and advantages of MOF and POP at the same time and has excellent catalytic ability. In this study, an efficient dual-functional core-shell composite MOF@POP with Lewis acid and Brønsted base sites was synthesized using the impregnation method in which MIL-101(Cr) was the core component and polymelamine formaldehyde (PMF) was the shell component. Most importantly, the obtained MIL-101(Cr)@PMF showed perfect catalytic activity in the deacetalization-Knoevenagel tandem reaction. In addition, it could still maintain ultrahigh physical and chemical stability.

19.
Mol Biol Rep ; 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-35980531

RESUMO

BACKGROUND: Spermatogenesis accompanied by self-renewal and differentiation of spermatogonia under complicated regulation is crucial for male fertility. Our previous study demonstrated that the loss of the B-lymphoma Mo-MLV insertion region 1 (BMI1) could cause male infertility and found a potential interaction between BMI1 and proline-rich protein 11 (PRR11); however, the specific co-regulatory effects of BMI1/PRR11 on spermatogonia maintenance remain unclear. METHODS AND RESULTS: The expression of PRR11 was downregulated in a mouse spermatogonia cell line (GC-1) via transfection with PRR11-siRNAs, and PRR11 knockdown was verified by real-time reverse transcriptase polymerase chain reaction (RT-qPCR). The proliferative activity of GC-1 cells was determined using the cell counting kit (CCK-8), colony formation, and 5-ethynyl-2-deoxyuridine (EdU) incorporation assay. A Transwell assay was performed to evaluate the effects of PRR11 on GC-1 cell migration. A terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to measure GC-1 cell apoptosis. Furthermore, co-immunoprecipitation, RT-qPCR, and western blot analyses were used for investigating the regulatory mechanisms involved in this regulation. It was found that downregulation of PRR11 could cause a marked inhibition of proliferation and migration and induced apoptosis in GC-1 cells. Moreover, silencing of PRR11 obviously led to a reduction in the BMI1 protein level. PRR11 was found to interact with BMII at the endogenous protein level. PRR11 knockdown produced a decrease in BMI1 protein stability via an increase in BMI1 ubiquitination after which derepression in the transcription of protein tyrosine phosphatase receptor type M (Ptprm) occurred. Importantly, knockdown of Ptprm in PRR11-deficient GC-1 cells led to a reversal of proliferation and migration of GC-1 cells. CONCLUSIONS: This study uncovered a novel mechanism by which PRR11 cooperated with BMI1 to facilitate GC-1 maintenance through targeting Ptprm. Our findings may provide a better understanding of the regulatory network in spermatogonia maintenance.

20.
Front Neurol ; 13: 896428, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937070

RESUMO

Background: As the treatment target, the imaging information and histologic characteristics of the thrombus may differ according to the stroke subtype. This study aimed to provide the correlative study of stroke etiology with the non-contrast CT, and histological composition of retrieved clots in acute ischemic stroke (AIS). Materials and Methods: A total of 94 patients with AIS who underwent the endovascular treatment with successfully retrieved clots from January 2017 to October 2020 were enrolled in the present study. Histological analysis was performed using hematoxylin and eosin (H&E) staining and immunostaining with CD3, CD20, CD105, and actin antibodies. CT obtained at the patients' admission was to measure the attenuation and volume of all thrombus. Results: A total of 94 subjects were included in this study. Fifty-six patients were classified as cardioembolic (CE), and 38 were classified with large-artery atherosclerosis (LAA). The subjects with LAA tend to exhibit higher actin and CD105 levels, and lower Hounsfield Unit (HU) values than subjects with CE. After adjusting for confounders, the actin was positively correlated with CD105 but not with HU values. Logistics regression shows actin was valuable for the prediction of LAA (OR, 1.148; 95% CI, 1.075-1.227; p < 0.001), even adjusted for age, sex, and intervention type (OR, 1.129; 95% CI, 1.048-1.216; p = 0.001), CT density and CD105 (OR, 1.161; 95% CI, 1.056-1.277; p = 0.002). Actin levels have a strong accuracy in differentiating LAA from CE, especially combined with CT density and CD105, which yielded a sensitivity of 63.2%, a specificity of 89.3%, with the area under the curve (AUC) at 0.821 (95% CI, 0.731-0.912). Conclusion: Our findings suggest that actin's level was a major factor differentiating atherothrombotic origin strokes from the cardioembolic stroke. Clinical Trial Registration: ChiCTR2100051173.

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