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1.
Food Chem ; 367: 130760, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34390911

RESUMO

Rapid volatile detection methods for seed vigour rely heavily on artificial ageing (AA), however the comparability of volatile organic compounds (VOCs) to natural ageing (NA) and practicability of the detection models were not well known. In this study, VOCs between AA and NA sweet corn seeds were compared and Partial Least Squares Regression (PLS-R) modelswere constructed based on AA to predict the seed vigour of NA. A total of 33 VOCs were identified, among which aldehydes showed the highest consistency between NA and AA. Furthermore, a AS-PLS-R model with variable importance in projection (VIP > 1) and Pearson Correlation Coefficient (r > 0.9) algorithms, which was built on 3 volatile markers: benzaldehyde monomer, n-nonanal, 1-butanol monomer, achieved the best performance (R2p of 0.901 and RMSEP of 0.050). Therefore, coupling Gas Chromatography- Ion Mobility Spectrometry (GC-IMS) with chemometrics can be an effective way to monitor and predict stored seeds vigour.


Assuntos
Compostos Orgânicos Voláteis , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Mobilidade Iônica , Análise dos Mínimos Quadrados , Sementes/química , Compostos Orgânicos Voláteis/análise
2.
Sci Total Environ ; : 150664, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34597546

RESUMO

The environmental impact, energy conservation, and economic cost are prominent decision criteria in municipal solid waste (MSW) management, among which trade-off relationships widely exist because of different features of pollutant treatment technologies. These three objectives should thereby be simultaneously considered in the design of technology combinations in MSW treatment system (MSWTS). In addition, comprehensive characterization of environmental impact of the whole MSWTS should cover the complex pollutants cross-media metabolism in the treatment of both MSW and subsequent secondary pollution. This study developed a multi-objective optimization model to select optimal technology solutions in MSWTS. Three objectives, the minimizations of total environmental impact calculated from pollutants cross-media metabolism perspective, net energy consumption, and total cost are optimized through the second generation of the Non-dominated Sorting Genetic Algorithm (NSGA-II). Final MSW management schemes under environment, energy, and cost preferences are obtained through Vlsekriterijumska Optimizacija I Kompromisno Resenje (VIKOR) method. This paper uses China's MSWTS as a case study and finds that Pareto optimal solutions can reduce the total environmental impact and the net energy consumption by 24.2% and 7.4% respectively, while increase the total cost by 18.2% in average, compared with the baseline scenario. The promotion of MSW biological treatment technologies, especially anaerobic digestion (AD), can effectively improve the environmental performance of MSWTS, while the current vigorous promotion of MSW incineration in China is not recommended. Sludge co-processing in cement kiln is highly promoted under all three types of management preferences. In summary, the proposed methodology can provide decision support for the optimal design of technology solutions in MSWTS.

3.
Anal Methods ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633400

RESUMO

In this work, a covalent organic framework (COF) TAPT-TFP-COF containing a triazine ring was prepared by a typical Schiff base condensation reaction of 1,3,5-tris-(4-aminophenyl)triazine (TAPT) and 1,3,5-triformyl phloroglucinol (TFP). The TAPT-TFP-COF and carboxyl-functionalized multi-wall carbon nanotubes (COOH-MWCNTs) were drip-coated on glassy carbon electrode respectively to develop a novel and simple electrochemical sensor in order to simultaneously detect dopamine (DA) and paracetamol (PA). COOH-MWCNTs interconnected the TAPT-TFP-COF and acted as bridges between the COF particles, which had a good synergistic effect and accelerated electron transfer. Under optimal conditions, linear responses were obtained over the concentration range 1-190 µM for DA and PA with limits of detection (LOD) of 0.14 µM and 0.19 µM, respectively. Furthermore, the fabricated sensor possesses outstanding repeatability and high selectivity, and can be applied for the determination of DA and PA in dopamine injection and acetaminophen drugs with satisfactory recoveries.

4.
BMC Health Serv Res ; 21(1): 1048, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34610843

RESUMO

BACKGROUND: In China, the primary health care (PHC) system has been designated responsible for control and prevention of COVID-19, but not treatment. Suspected COVID-19 cases presenting to PHC facilities must be transferred to specialist fever clinics. This study aims to understand the impact of COVID-19 on PHC delivery and on antibiotic prescribing at a community level in rural areas of central China. METHODS: Qualitative semi-structured interviews were conducted with 18 PHC practitioners and seven patients recruited from two township health centres and nine village clinics in two rural residential areas of Anhui province. Interviews were transcribed verbatim and analysed thematically. RESULTS: PHC practitioners reported a major shift in their work away from seeing and treating patients (due to government-mandated referral to specialist Covid clinics) to focus on the key public health roles of tracing, screening and educating in rural areas. The additional work, risk, and financial pressure that PHC practitioners faced, placed considerable strain on them, particularly those working in village clinics. Face to face PHC provision was reduced and there was no substitution with consultations by phone or app, which practitioners attributed to the fact that most of their patients were elderly and not willing or able to switch. Practitioners saw COVID-19 as outside of their area of expertise and very different to the non-COVID-19 respiratory tract infections that they frequently treated pre-pandemic. They reported that antibiotic prescribing was reduced overall because far fewer patients were attending rural PHC facilities, but otherwise their antibiotic prescribing practices remained unchanged. CONCLUSIONS: The COVID-19 pandemic had considerable impact on PHC in rural China. Practitioners took on substantial additional workload as part of epidemic control and fewer patients were seen in PHC. The reduction in patients seen and treated in PHC led to a reduction in antibiotic prescribing, although clinical practice remains unchanged. Since COVID-19 epidemic control work has been designated as a long-term task in China, rural PHC clinics now face the challenge of how to balance their principal clinical and increased public health roles and, in the case of the village clinics, remain financially viable.


Assuntos
Antibacterianos , COVID-19 , Idoso , Antibacterianos/uso terapêutico , China , Humanos , Pandemias , Atenção Primária à Saúde , SARS-CoV-2
5.
J Biol Chem ; : 101264, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34600885

RESUMO

CEBP transcription factors (TFs) are known to promote adipocyte differentiation; however, suppressors of CEBP TFs have not been reported thus far. Here, we find that homologous chromosome pairing protein Hop2 functions as an inhibitor for the TF CEBPα. We found that Hop2 mRNA is highly and specifically expressed in adipose tissue, and that ectopic Hop2 expression suppresses reporter activity induced by CEBP as revealed by DNA transfection. Recombinant and ectopically expressed Hop2 was shown to interact with CEBPα in pulldown and co-immunoprecipitation (co-IP) assays, and interaction between endogenous Hop2 and CEBPα were observed in the nuclei of 3T3 preadipocytes and adipocytes by immunofluorescence and co-IP of nuclear extracts. In addition, Hop2 stable overexpression in 3T3 preadipocytes inhibited adipocyte differentiation and adipocyte marker gene expression. These in vitro data suggest that Hop2 inhibits adipogenesis by suppressing CEBP-mediated transactivation. Consistent with a negative role for Hop2 in adipogenesis, ablation of Hop2 (Hop2-/-) in mice led to increased body weight, adipose volume, adipocyte size, and adipogenic marker gene expression. Adipogenic differentiation of isolated adipose-derived mesenchymal stem cells (aMSCs) showed a greater number of lipid droplet-containing colonies formed in Hop2-/- aMSC cultures than in wild type controls, which is associated with the increased expression of adipogenic marker genes. Finally, chromatin IP revealed a higher binding activity of endogenous CEBPα to PPARγ, a master adipogenic transcription factor, and a known CEBPα target gene. Therefore, our study identifies for the first time that Hop2 is an intrinsic suppressor of CEBPα and thus adipogenesis in adipocytes.

6.
J Vasc Interv Radiol ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34600129

RESUMO

PURPOSE: To investigate the safety and efficacy of locoregional therapy plus adoptive transfer of allogeneic gamma delta (γδ) T cells for patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS: Thirty HCC patients and 29 ICC patients were randomly assigned to receive locoregional therapy (HCC, Group A, n = 15; ICC, Group C; n = 15) or locoregional therapy plus γδ T cell therapy (HCC, Group B, n = 15; ICC, Group D, n = 14). Groups A and C only received locoregional ablation (cryoablation or irreversible electroporation), while Groups B and D received locoregional therapy followed by adoptive transfer of allogeneic γδ T cells. The primary endpoints were safety, distant progression-free survival (PFS), local PFS and overall survival (OS). RESULTS: The median distant PFS was significantly longer in the combined treatment groups than the locoregional treatment groups (HCC: 8 vs. 4 months, P = 0.04; ICC: 8 vs. 4 months, P = 0.021). There was no significant difference in local PFS between the two treatment modalities. HCC patients in the combined treatment group had a longer OS (median OS: 13 vs. 8 months, P = 0.029). However, there was no significant difference in OS in ICC patients between the two treatment modalities (median OS: 9.5 vs. 8 months, P = 0.546). All adverse events were manageable and no significant difference in the prevalence was observed between the groups. CONCLUSION: This study demonstrates that the novel combination therapy is safe with encouraging clinical efficacy against HCC and ICC.

7.
Bioengineered ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34595989

RESUMO

Present study was focuses on comparation of four typical fungicides in ginseng field to evaluated the impact of the different fungicides on the soil bacterial and fungal communities' composition and diversity by using high-throughput sequencing. Five treatments were designed and comprise carbendazim (D), dimethyl disulfide (E), dazomet (M), calcium cyanamide (S) and control (C). The application of fungicide obviously altered the dominant fungal and bacterial communities' distribution and remarkably decreased the diversity (1099-763 and 6457-2245). The most abundant Proteobacteria obvious degenerate in fungicides treated soil and minimum in E (0.09%) compare with control (25.72%). The relative abundance of Acidobacteria was reduced from 27.76 (C) to 7.14% after apply fungicide and minimum in E. The phylum Actinobacteria are both decomposers of organic matter and enemies of soil-borne pathogens, elevated from 11.62 to 51.54% and highest in E. The fungi community mainly distributed into Ascomycota that enriched from 66.09 to 88.21% and highest in M and E (88.21 and 85.10%), and Basidiomycota reduced from 21.13 to 3.23 % and lowest in M and E (5.27 and 3.23%). Overall, environmentally related fungicides decreased the diversity and altered the composition of bacterial and fungal communities, highest sensitivity present in dimethyl disulfide treated soil.

8.
J Affect Disord ; 296: 189-197, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34607060

RESUMO

BACKGROUND: The symptoms that patients with major depressive disorder (MDD) experience are the dominant contributing factors to its heavy disease burden. This study sought to identify key symptoms leading to disability in patients with MDD. METHODS: Subjects consisted of patients who had a 12-month MDD diagnosis based on the China Mental Health Survey (CMHS). World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was used to assess the degree of disability. The associations between depressive symptoms and disability were analyzed using a linear regression and logistic regression with a complex sampling design. RESULTS: Of the 32,552 community residents, 655 patients were diagnosed with 12-month MDD. The disability rate due to MDD was 1.06% (95% CI: 0.85%-1.28%) among adults in Chinese community and 50.7% (95% CI: 44.3%-57.1%) among MDD patients. Depression was associated with all functional losses measured by the WHODAS. Feelings of worthlessness in life or inappropriate guilt, and psychomotor agitation or retardation were the key symptoms related to disability. Economic status, co-morbidity of physical diseases or anxiety disorders were correlates of disability scores. LIMITATIONS: The disability rate might be underestimated due to the exclusion of MDD patients living in hospitals. The effect of treatments on disability was excluded. CONCLUSIONS: Psychological symptoms, not somatic symptoms, contribute to disability in MDD patients. Disability worsens when physical diseases or anxiety disorders are present. More attention could be paid to psychological symptoms, physical diseases, and anxiety disorders in MDD patients with disabilities.

9.
Biosens Bioelectron ; 196: 113686, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34628262

RESUMO

Artificial peroxisome is of critical importance to supersede natural peroxisome in fabricating protocell system and disease treatment. Nevertheless, developing feasible artificial peroxisome with various stable functions remains a monumental challenge. Nanozyme with multiple enzyme-like activities can mimic natural enzymes in peroxisome, which make it a prospective candidate for artificial peroxisome design. Herein, we prepared a nanozyme with multiple peroxisomal-like activities - Pd nanoparticles functionalized nitrogen-doped porous carbon-reduced graphene oxide (PdNPs/N-PC-rGO). Due to its sandwich-like structure, the incorporation of N heteroatoms and the synergistic effect between PdNPs and N-PC-rGO bi-support, the PdNPs/N-PC-rGO exhibited triple peroxisomal-like activities including oxidase (OXD), peroxidase (POD) and catalase (CAT), leading it a promising alternative for artificial peroxisome exploration. Furthermore, the PdNPs/N-PC-rGO showed high electrocatalytic activity, which could be employed for the detection of electrochemical active substances reduced glutathione (GSH). The PdNPs/N-PC-rGO modified electrode displayed a wide concentration range from 70 nM to 1500 µM, with a very low detection limit of 9.8 nM (S/N = 3). Therefore, PdNPs/N-PC-rGO was a promising nanozyme for various biotechnological applications such as artificial organelles, biosensing, cytoprotection, disease diagnosis and treatment.

10.
J Hazard Mater ; 423(Pt B): 127048, 2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34537642

RESUMO

Bifunctional oxygen-doped graphitic carbon nitride (OCN) was fabricated to activate peroxymonosulfate (PMS) for degrading imidacloprid (IMD). The modulated electronic structure of OCN promoted the adsorption, electron transfer, and formation of the redox site of PMS. The light absorption capacity, and the separation and migration speed of photogenerated carriers of OCN were increased. Consequently, 94.5% of IMD (3.0 mg/L) was removed by OCN-10/PMS process in 2.0 h. Compared with g-C3N4/PMS (0.048 h-1), the IMD degradation rate constant of OCN-10/Vis/PMS system (1.501 h-1) was increased by 30.3 times. The PMS oxidation on electron-deficient C atoms and holes, the PMS reduction around electron-rich O atoms and photogenerated electrons, and the multiple reactions of superoxide radical were the sources of the main active species singlet oxygen. Moreover, even under different pH conditions, coexisting anions, humic acid, and other neonicotinoid pesticides, the OCN-10/Vis/PMS system still showed acceptable applicability. Finally, mass spectrometry identified that hydroxylation and N-dealkylation of amines were the primary degradation pathways of IMD. This paper demonstrates an environmental-friendly combined activation strategy of PMS that can be operated day and night with low energy consumption, aiming to pave the way for developing metal-free photocatalysts for high-efficient environmental purification based on advanced oxidation coupling technology.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34582165

RESUMO

The development of methodologies for synthesizing carrier-transporting materials is critical for optoelectronic device fabrication. Amorphous metal oxides have emerged as potential carrier transport materials for perovskite tandem solar cells and flexible electronics due to their ease of fabrication and excellent electronic properties. However, perovskite solar cells employing amorphous metal oxides as the electron-transporting layers (ETLs) remain inefficient. This research describes a moderate dehydration reaction for the low-temperature synthesis of amorphous SnOx. We investigated this amorphous SnOx as the ETL for perovskite solar cells and demonstrated a maximum power conversion efficiency (PCE) of 20.4%, the greatest efficiency ever attained with an amorphous metal oxide ETL produced below 100 °C. Remarkably, the device maintained 85% of its initial efficiency for more than 4800 h. Furthermore, flexible perovskite solar cells based on this amorphous SnOx have a maximum PCE of 11.7%. Finally, this amorphous SnOx was used to fabricate LEDs and exhibited a maximum external quantum efficiency of over 3%.

12.
Environ Pollut ; 291: 118189, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34543954

RESUMO

Antibiotic resistance in environmental matrices becomes urgently significant for public health and has been considered as an emerging environmental contaminant. In this work, the ampicillin-resistant Escherichia coli (AR E. coli) and corresponding resistance genes (blaTEM-1) were effectively eliminated by the electrocatalytic process, and the dissemination risk of antibiotic resistance was also investigated. All the AR E. coli (∼8 log) was inactivated and 8.17 log blaTEM-1 was degraded by the carbon nanotubes/agarose/titanium (CNTs/AG/Ti) electrode within 30 min. AR E. coli was inactivated mainly attributing to the damage of cell membrane, which was attacked by reactive oxygen species and subsequent leakage of intracellular cytoplasm. The blaTEM-1 was degraded owing to the strand breaking in the process of electrocatalytic degradation. Furthermore, the dissemination risk of antibiotic resistance was effectively controlled after being electrocatalytic treatment. This study provided an effective electrocatalytic technology for the inactivation of antibiotic resistant bacteria and control of antibiotic resistance dissemination risk in the aqueous environment.

13.
BMC Psychiatry ; 21(1): 427, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465307

RESUMO

BACKGROUND: This study aimed to describe the prevalence and lifetime criteria profiles of DSM-5 alcohol use disorder (AUD) and the transitions from alcohol use to disorder in Chifeng, China. METHODS: Face-to-face interviews were conducted using Composite International Diagnostic Interview-3.0 (CIDI-3.0) among 4528 respondents in Chifeng. RESULTS: The weighted lifetime and 12-month prevalence of DSM-5 AUD were 3.03 and 1.05%, respectively. Mild lifetime AUD was the most prevalent severity level (69.53%). The two most common criteria were "failure to quit/cutdown" and "drinking more or for longer than intended." Lifetime prevalence was 65.59% for alcohol use, and 22.97% for regular drinking. Male and domestic violence were risk factors for the transition from alcohol use to regular drinking or AUD and from regular drinking to AUD. Younger age was risk factor for the transition to AUD from alcohol use or regular drinking. Poverty (OR = 2.49) was risk factor for the transition from alcohol use to regular drinking. The earlier drinkers were more likely to develop to regular drinking (OR = 2.11). CONCLUSION: AUD prevalence in Chifeng was not as high as that in Western countries. The study revealed that multiple risk factors might contribute to the transition across different stages of alcohol use. Further research should explore the underlying mechanisms.


Assuntos
Transtornos Relacionados ao Uso de Álcool , Alcoolismo , Consumo de Bebidas Alcoólicas/epidemiologia , Transtornos Relacionados ao Uso de Álcool/diagnóstico , Transtornos Relacionados ao Uso de Álcool/epidemiologia , Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , China/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Masculino , Prevalência , Fatores de Risco
14.
Cancer Med ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519169

RESUMO

BACKGROUND AND PURPOSE: We aimed to analyze the influence of target-related and clinical factors on lung tumor motion based on four-dimensional CT (4DCT), and clarify the motion based on subgroups in lung stereotactic body radiation therapy. MATERIALS AND METHODS: 4DCT image data of 267 tumors from 246 patients were analyzed. The coordinates in the left-right (LR), anterior-posterior (AP), and cranial-caudal (CC) directions of the center of mass (COM) of the gross tumor volumes in 10 phases of 4DCT were measured. The peak-to-peak COM displacement in the LR, AP, CC, and 3D directions was calculated. The influence of target-related and clinical factors on tumor motion was evaluated using multivariate analysis. RESULTS: The tumor segment location correlated with the tumor motion in each direction. Tumor size was predictive of tumor motion in the 3D (p = 0.023) and AP directions (p = 0.049). The tumor motion for metastatic tumors was smaller than that for primary tumors in the LR (p = 0.019) and AP directions (p = 0.008). The CC motion for pulmonary surgery recipients (3.8 ± 4.5 mm) was less than that for patients who had not undergone surgery (5.6 ± 5.4 mm), and no significant clinical factor was observed. BSA and BMI were positively correlated with the motion in the CC (p = 0.02) and LR directions (p = 0.002). CONCLUSION: The tumor segment location was a good predictor of tumor motion. A larger tumor tends to have a smaller motion. Patients with metastatic tumors or those who have undergone pulmonary surgery exhibited smaller and more unpredictable tumor motions, which required individual assessments. Thus, clinical factors can potentially predict tumor motion.

15.
Sci Total Environ ; 804: 150062, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34509854

RESUMO

The development of affordable and efficient technologies for the removal of pharmaceuticals and personal care products (PPCPs) from water has recently been the subject of extensive attention. In this study, a black phosphorus/graphitic carbon nitride (BP-g-C3N4) heterostructure is fabricated as an extremely active metal-free photocatalyst via a newly-developed exfoliation strategy. The BP-g-C3N4 shows an 11 times better decomposition rate of a representative PPCPs-type pollutant, indomethacin (IDM), compared to the widely-used P25 TiO2 under real-sunlight illumination. Also, its visible-light activity is even better than that of the best photocatalysts previously developed, but only consumes 1/10-1/4 of the catalyst. The results show that BP performs a cocatalyst-like behavior to catalyze the generation of reactive oxygen species, thus speeding up the decomposition of IDM. In addition, the BP-g-C3N4 photocatalyst also exhibits excellent IDM removal efficiency in authentic water matrices (tap water, surface water, and secondarily treated sewage effluent). Large-scale application demonstration under natural sunlight further reveals the practicality of BP-g-C3N4 for real-world water treatment operations. Our work will open up new possibilities in the development of purely metal-free photocatalysts for "green" environmental remediation applications.

16.
Elife ; 102021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34515635

RESUMO

The Amyloid Precursor Protein (APP) and its homologues are transmembrane proteins required for various aspects of neuronal development and activity, whose molecular function is unknown. Specifically, it is unclear whether APP acts as a receptor, and if so what its ligand(s) may be. We show that APP binds the Wnt ligands Wnt3a and Wnt5a and that this binding regulates APP protein levels. Wnt3a binding promotes full-length APP (flAPP) recycling and stability. In contrast, Wnt5a promotes APP targeting to lysosomal compartments and reduces flAPP levels. A conserved Cysteine-Rich Domain (CRD) in the extracellular portion of APP is required for Wnt binding, and deletion of the CRD abrogates the effects of Wnts on flAPP levels and trafficking. Finally, loss of APP results in increased axonal and reduced dendritic growth of mouse embryonic primary cortical neurons. This phenotype can be cell-autonomously rescued by full length, but not CRD-deleted, APP and regulated by Wnt ligands in a CRD-dependent manner.

17.
Aging (Albany NY) ; 13(17): 21102-21121, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508613

RESUMO

BGB-3111, a novel Bruton's tyrosine kinase (BTK) inhibitor, shows promising anti-cancer effects in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), and Waldenstrom macroglobulinemia (WM). This study aimed to investigate the anti-cancer effects of BGB-3111 combined with bortezomib (BTZ) against the BTK-expressing MCL. We found that BTK, which was overexpressed in 59.4% of patients with MCL, was mainly characterized by high Ki67 and elevated MIPI scores. BGB-3111 strongly inhibited cell proliferation, induced cell cycle arrest in the G1/G0-phase, and promoted cell apoptosis in the MCL cells expressing BTK. BGB-3111 provides better safety than another BTK inhibitor, ibrutinib as ibrutinib inhibits the inducible T-cell kinase (ITK) as an off-target effect but BGB-3111 does not inhibit ITK. Low doses of BTZ enhanced the anti-cancer effect induced by the low dose of BGB-3111 by downregulating the expression levels of PARP and Bcl-2 and increasing the expression levels of cleaved PARP and cleaved caspase-9. In addition, low doses of BGB-3111, but not of BTZ, inhibited BTK phosphorylation. However, low-doses of BTZ strengthened the anti-cancer effect induced by the low-doses of BGB-3111 via synergistically suppressing the IκBα and P65 phosphorylation. Taken together, our findings validate that BGB-3111 is a novel and effective BTK inhibitor for MCL-expressing BTK. Hence, it can be harnessed as a potential therapeutic strategy through a combinatorial treatment comprising low-dose BGB-3111 and low-dose BTZ to gain strong anti-cancer effects and better safety for MCL patients.

18.
Toxicology ; 462: 152930, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34492313

RESUMO

Emodin is widely present in Chinese herbs with broad application prospects, however, the conflicting reports of its hepatotoxicity have created a concern. It was therefore aimed to develop practical models to elucidate the outcome of CYP450 biotransformation on emodin. HepG2 and rat liver microsomes (RLM) coculture system was first utilized for prediction. It was found that emodin (35 µM)-mediated cytotoxicity was alleviated only when the cofactor of CYP450 NADPH (1 mM) was present. Similarly, both the pan-CYP450 inhibitor 1-aminobenzotriazole (ABT) (2 mM) and the heat-inactivated liver microsomes completely abolished the protective effect of RLM (0.75 mg/mL). Consistently, ABT significantly increased the toxicity of emodin in primary rat liver cells. Along similar lines, only the monohydroxylation metabolite M3 that accounted for neglectable amount of the whole metabolites showed similar toxicity to emodin, both M1 and M2 exhibited far less toxcity than emodin in THLE-2 cells. In vivo study further supported that ABT (50 mg/kg, s.c.) aggravated the hepatotoxicity of emodin (80 mg/kg, i.p.) on mice, as emodin treatment only mediated slight increase of liver index and histological score likely due to the metabolic detoxication of emodin, whereas ABT co-administration resulted in severe liver injury as reflected by the dramatic increase of the liver index value, serum ALT and AST levels, and histopathological score. Moreover, it was explored that ROS generation together with the electrophilicity of emodin contributed to its hepatotoxicity. These findings not only provided a clear evidence of the metabolic detoxification of emodin, but also shed a light on the hepatotoxic mechanisms of emodin, which would lay a solid foundation for the rational application of emodin in the future.

19.
Infect Genet Evol ; 95: 105082, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34520874

RESUMO

This study was to find out novel miRNAs whether could be used as diagnostic or prognostic biomarkers in sepsis. We used miRNAs microarray assays and further confirmed the levels of miRNAs in 151 septic patients' plasma. 56 miRNAs were up-regulated and 74 miRNAs down-regulated in septic patients compared with the healthy volunteers. But only miR-519c-5p and miR-3622b-3p were up-regulated in both septic and septic shock patients. The levels of miR-519c-5p and miR-3622b-3p were statistically higher in 151 septic patients than healthy controls on day 1. The AUC for miR-519c-5p was 0.79 (95% CI, 0.688-0.892, p = 0.001) in the diagnosis of sepsis, and the AUC for miR-3622b-3p 0.752 (95% CI, 0.622-0.881, p = 0.003). The AUC for the combination of these two miRNAs was 0.831 (95% CI, 0.74-0.923, p < 0.001). Besides, the AUC for miR-519c-5p was 0.597 (p = 0.043) in predicting 28-day mortality. MiR-519c-5p, miR-3622b-3p were novel biomarkers for diagnosing septic patients. High miR-519c-5p levels suggest a worse short-term prognosis. CLINICAL TRIAL REGISTRATION INFORMATION: Name of the registry: Diagnostic and prognostic value of circulating miRNA in patients with sepsis; Trial registration ID: ChiCTR-DDD-17013150; registered 30 October 2017; http://www.chictr.org.cn/edit.aspx?pid=22528&htm=4.

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