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1.
J Agric Food Chem ; 69(28): 8008-8016, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34232649

RESUMO

Fiber coating is a key part of solid-phase microextraction (SPME) technology, and it determines the selectivity, sensitivity, and reproducibility of the analytical method. A ketoenamine covalent organic framework called Tp-Azo-COF with rich electronegative N atoms was prepared as an SPME coating in this work. The Tp-Azo-COF coating had a large surface area of 1218 m2 g-1 and good thermal and chemical stability, and it was applied for the extraction of organochlorine pesticides (OCPs). According to quantum chemistry calculations, the adsorption affinity of the Tp-Azo-COF coating for five OCPs was primarily affected by the halogen bond and hydrophobicity interaction. The extraction efficiencies of the Tp-Azo-COF coating for five OCPs were higher than those of three commercial SPME fiber coatings, and the enrichment factors ranged from 1061 to 3693. When combined with gas chromatography-tandem mass spectrometry, a wide linear range (0.1-1000 ng L-1), low limits of detection (0.002-0.08 ng L-1), and good fiber-to-fiber accuracy (4.3-10.9%) were achieved under optimal conditions. Moreover, the applicability of the developed method was evaluated by analyzing four samples (milk, green tea, tap water, and well water), and the recoveries were in the range of 83.4-101.6%, with relative standard deviations <8.6%. This research extends the application of the stabilized ketoenamine COF as a sample enrichment probe for OCP analysis.

2.
Clin Exp Nephrol ; 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34231109

RESUMO

OBJECTIVE: Lupus nephritis is one of the most common and severe systemic lupus erythematosus complications. However, the pathogenesis of lupus nephritis is still poorly understood. Increasing evidence has shown that microRNAs (miRNAs) are extensively involved in the pathophysiology of autoimmune diseases. NZBWF1 is the classical mouse model of lupus nephritis. The present study aimed to investigate the expression profiling of mRNA and miRNAs of NZBWF1 mice with lupus nephritis using microarray, and explored the potential molecular mechanism of miRNA. METHODS: miRNA and mRNA microarrays were performed to identify miRNA and mRNA expression changes between pre-diseased (8-week-old) NZBWF1 mice and diseased NZBWF1 mice with lupus nephritis (28-week-old). Quantitative polymerase chain reaction (qPCR) validated these results. The target of miRNA was confirmed through a dual-luciferase reporter and stimulated mesangial cells experiment. RESULTS: The combined miRNA and mRNA analysis identified 43 differentially expressed miRNAs and 1796 differentially expressed mRNAs between pre-disease (8-week-old) (n = 4) and diseased (28-week-old) NZBWF1 mice. We found that miR-1968-5p was significantly decreased, and csf1 mRNA was significantly increased in lupus nephritis mouse and verified by RT-PCR. csf1 has been demonstrated to play important roles in SLE. Bioinformatics analysis predicted that the csf1 was a potential target gene of miR-1968-5p. A dual-luciferase reporter assay confirmed the target binding. In cell experiments, overexpression or knockdown of miR resulted in a decrease or increase of csf1 expression, respectively. CONCLUSION: These results suggest that miR-1968-5p may be involved in the pathogenesis of lupus nephritis of NZBWF1 mice by targeting csf1.

3.
Sensors (Basel) ; 21(11)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34200038

RESUMO

Image intensifiers are used internationally as advanced military night-vision devices. They have better imaging performance in low-light-level conditions than CMOS/CCD. The intensified CMOS (ICMOS) was developed to satisfy the digital demand of image intensifiers. In order to make the ICMOS capable of color imaging in low-light-level conditions, a liquid-crystal tunable filter based color imaging ICMOS was developed. Due to the time-division color imaging scheme, motion artifacts may be introduced when a moving target is in the scene. To solve this problem, a deformable kernel prediction neural network (DKPNN) is proposed for joint denoising and motion artifact removal, and a data generation method which generates images with color-channel motion artifacts is also proposed to train the DKPNN. The results show that, compared with other denoising methods, the proposed DKPNN performed better both on generated noisy data and on real noisy data. Therefore, the proposed DKPNN is more suitable for color ICMOS denoising and motion artifact removal. A new exploration was made for low-light-level color imaging schemes.


Assuntos
Artefatos , Redes Neurais de Computação , Movimento (Física)
4.
Adv Sci (Weinh) ; 8(13): 2100209, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34258163

RESUMO

Phenotypic polarization of macrophages is regulated by a milieu of cues in the local tissue microenvironment. Currently, little is known about how the intrinsic regulators modulate proinflammatory (M1) versus prohealing (M2) macrophages activation. Here, it is observed that insulin-like growth factor 2 messenger RNA (mRNA)-binding protein 2 (IGF2BP2)-deleted macrophages exhibit enhanced M1 phenotype and promote dextran sulfate sodium induced colitis development. However, the IGF2BP2-/- macrophages are refractory to interleukin-4 (IL-4) induced activation and alleviate cockroach extract induced pulmonary allergic inflammation. Molecular studies indicate that IGF2BP2 switches M1 macrophages to M2 activation by targeting tuberous sclerosis 1 via an N6-methyladenosine (m6A)-dependent manner. Additionally, it is also shown a signal transducer and activators of transcription 6 (STAT6)-high mobility group AT-hook 2-IGF2BP2-peroxisome proliferator activated receptor-γ axis involves in M2 macrophages differentiation. These findings highlight a key role of IGF2BP2 in regulation of macrophages activation and imply a potential therapeutic target of macrophages in the inflammatory diseases.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34269505

RESUMO

Luminescent covalent organic frameworks (COFs) find promising applications in chemical sensing, photocatalysis, and optoelectronic devices, however, the majority of COFs are non or weakly emissive owing to the aggregation-caused quenching (ACQ) or the molecular thermal motion-based energy dissipation. Here, we report a previously unperceived approach to improve luminescence performance of COFs by introducing isotope effect, which is achieved through substitution of hydrogen from high-frequency oscillators X-H (X = O, N, C) by heavier isotope deuterium. Combining the "bottom-up" and in situ deuteration methods generates the first deuterated COF, which exhibits an impressively 19-fold enhancement in quantum yield over that of the non-deuterated counterpart. These results are interpreted by theoretical calculations as the consequence of slower C/N-D and OD···O vibrations that impede the nonradiative deactivation process. The proposed strategy is proved applicable to many other types of emissive COFs.

6.
Clin Neurol Neurosurg ; 207: 106796, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34246993

RESUMO

OBJECTIVE: Uncertainty exists over the prognostic significance of low arterial oxygen saturation (SaO2) in acute stroke. We aimed to determine the strength of association of SaO2 and adverse outcomes among participants of the international Head Positioning in acute Stroke Trial (HeadPoST). METHODS: Post-hoc analyzes of HeadPoST, a pragmatic cluster-crossover randomized trial of lying flat versus sitting up head positioning in 11,093 patients (age ≥18 years) with acute stroke at 114 hospitals in 9 countries during 2015-2016. Associations of the lowest recorded SaO2 level, as a continuous measure and as a cut-point for desaturation (SaO2 <93%), in the first 24 h and clinical outcomes of death or dependency (modified Rankin scale [mRS] scores 3-6) and any serious adverse event (SAE) at 90 days, were assessed in generalized linear mixed models adjusted for baseline and in-hospital management confounders. RESULTS: There was an inverse J-shaped association between SaO2 and death or dependency, with a nadir for optimal outcome at 96-97%. Patients with SaO2 desaturation were older, and had greater neurological impairment, premorbid disability and cardiorespiratory disease. Desaturation was not clearly associated with death or dependency (adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 0.95-1.48) but was with SAEs (aOR 1.34, 95% CI 1.07-1.68), without heterogeneity by head position, cardiac-respiratory comorbidity, or other pre-specified subgroups. CONCLUSIONS: Any change in SaO2 outside of 96-97% is associated with poorer outcome after acute stroke. CLINICAL TRIAL REGISTRATION: HeadPoST is registered at ClinicalTrials.gov (NCT02162017).

7.
Virol J ; 18(1): 132, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193186

RESUMO

BACKGROUND: To investigate the relationship between polymorphism of scavenger receptor class B member 2 (SCARB2) gene and clinical severity of enterovirus (EV)-71 associated hand-foot-mouth disease (HFMD). METHODS: Among the 100 recruited cases, 56 were in the severe HFMD group (case group) and 44 were in the general HFMD group (control group). By screening functional single nucleotide polymorphisms (SNPs) and hot SNPs, and performing SNP site optimization, some SNP sites of SCARB2 gene were selected for analysis. Genotyping was performed using a MassArray platform. PLINK software was used for statistical processing and analysis of the correlation differences between the mutant genotypes in the severe and general HFMD groups. The relationship between the SNPs and clinical severity of enterovirus (EV)-71 associated HFMD was assessed. RESULTS: 28 SNPs in SCARB2 were selected by site optimization. Then three loci were not in agreement with the minor allele frequency (MAF) in the 1000 Han Chinese in Beijing (CHB) dataset. Another three loci could not be detected. Nine loci were not suitable for further analysis (MAF < 0.01 and Hardy-Weinberg [HWE] P < 0.001). A total of 13 sites were subsequently analyzed. Through Fisher analysis, the frequency of the rs6812193 T allele was 0.134 and 0.034 in the severe and general HFMD groups, respectively (P 0.023 < 0.05, odds ratio [OR] 4.381 > 1). Logistic regression analysis of rs6812193 T alleles between the severe and general HFMD groups, respectively (P 0.023 < 0.05, OR 4.412 > 1, L95 1.210 > 1). Genotype logistic regression analysis of the rs6812193 alleles CT + TT versus CC gave an OR of 4.56 (95% confidence interval [95% CI] 1.22-17.04, P = 0.012). CONCLUSION: The rs6812193 T allele was a susceptibility SNP for SHFMD, and the rs6812193 polymorphism might be significantly associated with the susceptibility to EV-71 infection.

8.
Phys Rev Lett ; 126(24): 246601, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34213928

RESUMO

The magnetic van der Waals crystals MnBi_{2}Te_{4}/(Bi_{2}Te_{3})_{n} have drawn significant attention due to their rich topological properties and the tunability by external magnetic field. Although the MnBi_{2}Te_{4}/(Bi_{2}Te_{3})_{n} family have been intensively studied in the past few years, their close relatives, the MnSb_{2}Te_{4}/(Sb_{2}Te_{3})_{n} family, remain much less explored. In this work, combining magnetotransport measurements, angle-resolved photoemission spectroscopy, and first principles calculations, we find that MnSb_{4}Te_{7}, the n=1 member of the MnSb_{2}Te_{4}/(Sb_{2}Te_{3})_{n} family, is a magnetic topological system with versatile topological phases that can be manipulated by both carrier doping and magnetic field. Our calculations unveil that its A-type antiferromagnetic (AFM) ground state stays in a Z_{2} AFM topological insulator phase, which can be converted to an inversion-symmetry-protected axion insulator phase when in the ferromagnetic (FM) state. Moreover, when this system in the FM phase is slightly carrier doped on either the electron or hole side, it becomes a Weyl semimetal with multiple Weyl nodes in the highest valence bands and lowest conduction bands, which are manifested by the measured notable anomalous Hall effect. Our work thus introduces a new magnetic topological material with different topological phases that are highly tunable by carrier doping or magnetic field.

9.
Mediators Inflamm ; 2021: 9921897, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220338

RESUMO

Excessive release of cytokines such as IL-1ß and other inflammatory mediators synthesized and secreted by macrophages is the fundamental link of uncontrolled inflammatory response in sepsis. 17ß-Estradiol (E2) plays anti-inflammatory and vascular protective effects by regulating leukocyte infiltration and the expression of chemokines or cytokines induced by injury. However, the role of E2 in the inflammatory response of macrophages in sepsis and its mechanism are still not fully understood. In the present study, we show that E2 alleviates vascular inflammation in sepsis mice induced by cecal ligation puncture (CLP). E2 significantly decreases RAW 264.7 cell inflammation response by downregulating the expression of NLRP3. Furthermore, we found that miR-29a-5p was significantly downregulated in LPS-treated macrophages. Treating RAW 264.7 cells with E2 markedly upregulated the miR-29a-5p expression level. More importantly, we demonstrated that miR-29a-5p repressed NLRP3 expression by directly targeting its 3'-UTR. Loss- and gain-of-function experiments revealed that transfection of the miR-29a-5p mimic abrogates LPS-induced macrophage inflammation. Moreover, depletion of miR-29a-5p by its inhibitor largely promotes LPS-induced macrophage inflammation. In summary, miR-29a-5p upregulation induced by E2 alleviated RAW 264.7 cell inflammation response by aggravating miR-29a-5p repression of NLRP3 expression. E2 exerts significant anti-inflammatory efficacy in macrophages by regulating the miR-29a-5p/NLRP3 axis. Targeting miR-29a-5p may be a novel therapeutic strategy to suppress sepsis-induced vascular inflammation.

11.
Libyan J Med ; 16(1): 1943924, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34151749

RESUMO

Quercetin (QN) is a naturally occurring phenolic compound found largely in vegetables and fruits. Lycopene (LY) is yet another natural phytocompound, found abundantly in red-colored fruits and vegetables. Both have been reported to have beneficial activities in humans. In this study, we document in vivo experimental model for isoproterenol (ISO) cardiac injury toxicity in Sprague-Dawley (SD) rats and treatment with a combined optimized concentration of quercetin and lycopene (QL). Male SD rats of different groups were treated with QL (80 mg/kg QN and 3 mg/kg LY together p.o.) for 10 days with ISO administration (100 mg/kg i.p.) on days 7 and 8. After experimental period, CK-MB, TROP, AST, ALT, LDH, GST, GPx, CAT, SOD, Vit.E, Vit. C, GSH, GSSG and MDA were estimated. SD rats administered with ISO showed an obvious rise in the serum marker enzyme levels and tissue oxidative stress markers (MDA and GSSG). Furthermore, marked reductions in the body weight and increases enzymic and non-enzymic antioxidant levels were noticed. Histological features of the heart also indicated a disruption in the cardiac myofibrils structure of ISO-intoxicated rats. Also, quantitative PCR analysis revealed an involvement of antioxidant and related pathway genes such as Nrf2, HO-1, NQO1, GSTµ, SOD1, SOD2, CAT and BCl-2 genes. QL pretreatment prevented all these adverse effects of ISO cardiotoxicity and significantly reduced the myocardial damage. Decrease in oxidative stress was observed, possibly through alterations in the expression levels of enzymic antioxidant genes (GSTµ, SOD1, SOD2 and CAT). In general, QL exert a strong protective effect through the modulations in enzymic antioxidant activity and associated molecular pathways-regulating effect in cardiovascular disease.

12.
Int J Psychophysiol ; 167: 38-46, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34174361

RESUMO

This study aimed to investigate the moderating effect of the desire for forgiveness on the association between relationship closeness and interpersonal forgiveness using event-related potentials (ERPs). We recruited forty student participants (20 males and 20 females) to complete the modified Taylor Aggression Paradigm (TAP), which was used to induce the offensive experience and record the victim's level of reactive aggression toward the offenders. Results indicated that for the internal intention of forgiveness behavior, when the desire for forgiveness was not expressed, participants were more forgiving of close offenders than strangers; when the desire for forgiveness was expressed, the internal intention of forgiveness behavior for strangers was similar to that for close offenders. Regarding the external performance of forgiveness behavior, whether the offender expressed the desire for forgiveness or not, participants exhibited more external performance of forgiveness behaviors toward the close offenders than the strangers. Furthermore, the decision-related negativity (DRN)-a negative component associated with aggressiveness-was larger when participants were considering the punishment of strangers when no desire for forgiveness was expressed. There was no significant difference when the desire for forgiveness was expressed. Moreover, the feedback-related negativity (FRN)-a negative component reflecting the evaluation of the valence of an outcome-was larger when participants lost a trial against strangers when no desire for forgiveness was expressed. No such difference was observed in both opponents when the desire for forgiveness was expressed. These findings confirmed that the desire for forgiveness moderated the association between relationship closeness and interpersonal forgiveness.

13.
Wien Klin Wochenschr ; 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: covidwho-1274847

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection has caused huge impacts on all of people's lives and health systems. In response to the COVID-19 pandemic, China was the first country to impose lockdown. We aimed to study the influence of COVID-19 on the outpatient visits of rheumatic patients in a non-outbreak area of China. METHODS: We selected three provincial or ministerial hospitals in Jinan, and collected the outpatient appointments data in rheumatology and immunology departments during the Shandong Province first-level public health emergency response period from 25 January 2020 to 8 March 2020. RESULTS: In the early stage, the number of outpatient appointments in the rheumatology and immunology departments of the three provincial or ministerial hospitals were significantly reduced, and gradually restored in the late stage. It showed that in the face of major infectious diseases, strict quarantine measures with the cooperation of the public not only controls the epidemic in a short time, but also lifts the quarantine measures and opens general outpatient clinics in hospitals as soon as possible, thus minimizing the impact on other patients. INTERPRETATION: The impact on the western hospital was greater than that on the Chinese medicine hospital, and the impact on the back-up designated hospitals for COVID-19 was the greatest. Online appointment can reduce the risk of infection in outpatients, but not completely solve the follow-up problem of rheumatic patients. Telemedicine provides a new solution for both management of rheumatic patients and control of COVID-19.

14.
Ecotoxicol Environ Saf ; 221: 112421, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34147865

RESUMO

A wide variety of organic micropollutants in drinking water pose a serious threat to human health. This study was aimed to reveal the characteristics of organic micropollution profiles in water from a drinking water treatment plant (DWTP) in the Yangtze River Delta, China and investigate the mutagenicity, health risk and disease burden through mixed exposure to micropollutants in water. The presence of organic micropollutants in seven categories in organic extracts (OEs) of water from the DWTP was determined, and Ames test was conducted to test the mutagenic effect of OEs. Meanwhile, health risk of exposure to organic micropollutants in finished water through three exposure routes (ingestion, dermal absorption and inhalation) was assessed with the method proposed by U.S. EPA, and disability-adjusted life years (DALYs) were combined to estimate the disease burden of cancer based on the carcinogenic risk (CR) assessment. The results showed that 28 organic micropollutants were detected in the raw and finished water at total concentrations of 967.28 ng/L and 1073.45 ng/L, respectively, of which phthalate esters (PAEs) were the dominant category (95.79% in the raw water and 96.61% in the finished water). Although the results of the Ames test for OEs were negative and the non-carcinogenic hazard index of the organic micropollutants in the finished water was less than 1 in all age groups, the total CR was 2.17 × 10-5, higher than the negligible risk level (1.00 × 10-6). The total DALYs caused by the organic micropollutants in the finished water was 2945.59 person-years, and the average individual DALYs was 2.21 × 10-6 per person-year (ppy), which was 2.21 times the reference risk level (1.00 × 10-6 ppy) defined by the WHO. Exposure to nitrosamines (NAms) was the major contributor to the total CR (92.06%) and average individual DALYs (94.58%). This study demonstrated that despite the negative result of the mutagenicity test with TA98 and TA100 strains, the health risk of exposure to organic micropollutants in drinking water should not be neglected.


Assuntos
Água Potável/análise , Mutagênicos/análise , Compostos Orgânicos/análise , Poluentes Químicos da Água/análise , China , Efeitos Psicossociais da Doença , Monitoramento Ambiental , Humanos , Testes de Mutagenicidade , Mutagênicos/toxicidade , Compostos Orgânicos/toxicidade , Medição de Risco , Rios , Poluentes Químicos da Água/toxicidade , Purificação da Água
15.
Med Sci Monit ; 27: e929851, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34181636

RESUMO

BACKGROUND Through January 2021, the novel coronavirus (COVID-19) continued to create significant pressure on medical staff who have worked to treat patients with the disease and control its spread. This study aimed to increase understanding of the situation and influencing factors of nurses' work interruption in Wuhan's isolation ward during the COVID-19 pandemic. MATERIAL AND METHODS A self-designed general situation questionnaire and work interruption questionnaire were used to survey 160 nurses from Beijing, Chongqing, and Jilin who worked during the COVID-19 pandemic in Wuhan in March 2020. The questionnaire could only be answered once by each nurse via a WeChat account. The submitted answers were verified by 2 researchers. RESULTS The results showed that the rate of interruption of work among nurses in the isolation ward was 25%, and the rate of nurses experiencing a negative experience was 96.9%. The results of univariate analysis showed that the following factors were related to the work interruption of the nurses in the isolation ward (all P<0.05): emergency public incident training; emergency public incident treatment experience; knowledge of COVID-19 pneumonia; hours worked per shift in the quarantine area; and negative physiologic experience. Logistic regression analysis showed that negative experience, hours worked per shift, and emergency public incident training were the independent factors influencing work interruption among nurses in the isolation wards. CONCLUSIONS The incidence of interruption of work among nurses in the isolation ward was 25%. Negative experiences, long working hours per shift, and lack of emergency public incident training made the nurses more prone to work interruption.


Assuntos
COVID-19/enfermagem , Enfermeiras e Enfermeiros/economia , Adulto , Pequim/epidemiologia , COVID-19/economia , China/epidemiologia , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros/provisão & distribuição , Enfermeiras e Enfermeiros/tendências , Pandemias , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Inquéritos e Questionários , Carga de Trabalho/economia
16.
Med Sci Monit ; 27: e929851, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: covidwho-1296217

RESUMO

BACKGROUND Through January 2021, the novel coronavirus (COVID-19) continued to create significant pressure on medical staff who have worked to treat patients with the disease and control its spread. This study aimed to increase understanding of the situation and influencing factors of nurses' work interruption in Wuhan's isolation ward during the COVID-19 pandemic. MATERIAL AND METHODS A self-designed general situation questionnaire and work interruption questionnaire were used to survey 160 nurses from Beijing, Chongqing, and Jilin who worked during the COVID-19 pandemic in Wuhan in March 2020. The questionnaire could only be answered once by each nurse via a WeChat account. The submitted answers were verified by 2 researchers. RESULTS The results showed that the rate of interruption of work among nurses in the isolation ward was 25%, and the rate of nurses experiencing a negative experience was 96.9%. The results of univariate analysis showed that the following factors were related to the work interruption of the nurses in the isolation ward (all P<0.05): emergency public incident training; emergency public incident treatment experience; knowledge of COVID-19 pneumonia; hours worked per shift in the quarantine area; and negative physiologic experience. Logistic regression analysis showed that negative experience, hours worked per shift, and emergency public incident training were the independent factors influencing work interruption among nurses in the isolation wards. CONCLUSIONS The incidence of interruption of work among nurses in the isolation ward was 25%. Negative experiences, long working hours per shift, and lack of emergency public incident training made the nurses more prone to work interruption.


Assuntos
COVID-19/enfermagem , Enfermeiras e Enfermeiros/economia , Adulto , Pequim/epidemiologia , COVID-19/economia , China/epidemiologia , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros/provisão & distribuição , Enfermeiras e Enfermeiros/tendências , Pandemias , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Inquéritos e Questionários , Carga de Trabalho/economia
17.
Oncogene ; 40(28): 4695-4708, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34140641

RESUMO

Oxaliplatin (oxa) is widely used in the treatment of colorectal cancer (CRC), but the development of oxaliplatin resistance is a major obstacle to the therapeutic efficacy in patients. MicroRNAs (miRNAs), endogenous noncoding RNAs measuring between 22 and 24 nucleotides, have been shown to be involved in the development of CRC drug resistance. However, the mechanism by which differentially expressed miRNAs induce chemotherapy resistance in CRC has not been fully elucidated to date. Here, we showed the differentially expressed miRNAs in oxaliplatin-sensitive and oxaliplatin-resistant CRC cells through miRNA microarray technology and found that miR-135b-5p was significantly increased in oxaliplatin-resistant cells. And miR-135b-5p was increased in the serum of colorectal cancer patients. More importantly, the miR-135b-5p level in the serum of oxaliplatin-resistant patients was further increased compared to that of oxaliplatin-sensitive patients. Recent studies have shown that protective autophagy is an important mechanism that promotes drug resistance in tumors. The potential role of miR-135b-5p in inducing protective autophagy and promoting oxaliplatin resistance was evaluated in two stable oxaliplatin-resistant CRC cell lines and their parental cells. We further identified MUL1 as a direct downstream target of miR-135b-5p and showed that MUL1 could degrade the key molecule of autophagy, ULK1, through ubiquitination. Mouse xenograft models were adopted to evaluate the correlation between miR-135b-5p and oxaliplatin-induced autophagy in vivo. Furthermore, we also investigated the regulatory factors for the upregulation of miR-135b-5p in CRC cells under oxaliplatin chemotoxicity. These results indicated that miR-135b-5p upregulation in colorectal cancer could induce protective autophagy through the MUL1/ULK1 signaling pathway and promote oxaliplatin resistance. Targeting miR-135b-5p may provide a new treatment strategy for reversing oxaliplatin resistance in CRC.

18.
Cerebrovasc Dis ; : 1-7, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34153968

RESUMO

BACKGROUND AND PURPOSE: As outcomes for acute ischemic stroke (AIS) vary according to clinical profile and management approaches, we aimed to determine disparities in clinical outcomes between Asian and non-Asian participants of the international, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED). METHODS: ENCHANTED was a multicenter, prospective, partial-factorial, randomized, open trial of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) alteplase, and intensive (target systolic blood pressure [SBP] 130-140 mm Hg) or guideline-recommended (<180 mm Hg) BP management, in thrombolysis-eligible AIS patients. Logistic regression models were used to examine the associations with outcomes of death or disability (modified Rankin scale [mRS] scores 2-6), major disability (mRS 3-5), death, and intracranial hemorrhage (ICH), with adjustment prognostic factors, alteplase dose, and mean SBP over 1-24 h. RESULTS: Among 4,551 thrombolyzed AIS patients (mean age 66.7 years, 37.8% female), there were 65.4% Asians who were younger, fewer female, and with less atrial fibrillation, hypercholesterolemia, premorbid symptoms, and concomitant antihypertensive, antithrombotic and statin treatment, and more prior stroke, compared to non-Asians. Frequencies of hypertension, coronary artery disease, and diabetes mellitus were comparable between groups. Asian patients were less likely to be admitted to an acute stroke unit and receive early mobilization by a therapist or rehabilitation but more likely to receive intensive care. There were no significant differences between Asians and non-Asians in functional outcome (defined by mRS scores 2-6 or 3-5; adjusted odds ratio [OR] 1.00, 95% confidence interval [CI] 0.85-1.19 [p = 0.958] and OR 0.95, 95% CI 0.80-1.13 [p = 0.572], respectively), or death (OR 1.25, 95% CI 0.95-1.65; p = 0.116), despite Asians having greater odds of ICH (OR 1.51, 95% CI 1.23-1.86; p = 0.0001) and neurological deterioration within 24 h (OR 1.58, 95% CI 1.18-2.12; p = 0.002). CONCLUSIONS: Within the context of an international clinical trial of thrombolyzed AIS patients, demography, risk factors, management, and odds of early neurological deterioration and ICH, all differ between Asian and non-Asian participants. However, patterns of functional recovery are similar between these major regional groups.

19.
Int J Stroke ; : 17474930211025436, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34096413

RESUMO

BACKGROUND: We explored the influence of low-dose intravenous alteplase and intensive blood pressure lowering on outcomes of acute ischemic stroke according to status/location of vascular obstruction in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: ENCHANTED was a multicenter, quasi-factorial, randomized trial to determine efficacy and safety of low- versus standard-dose intravenous alteplase and intensive- versus guideline-recommended blood pressure lowering in acute ischemic stroke patients. In those who had baseline computed tomography or magnetic resonance imaging angiography, the degree of vascular occlusion was grouped according to being no (NVO), medium (MVO), or large (LVO). Logistic regression models were used to determine 90-day outcomes (modified Rankin scale [mRS] shift [primary], other mRS cut-scores, intracranial hemorrhage, early neurologic deterioration, and recanalization) by vascular obstruction status/site. Heterogeneity in associations for outcomes across subgroups was estimated by adding an interaction term to the models. RESULTS: There were 940 participants: 607 in alteplase arm only, 243 in blood pressure arm only, and 90 assigned to both arms. Compared to the NVO group, functional outcome was worse in LVO (mRS shift, adjusted OR [95% CI] 2.13 [1.56-2.90]) but comparable in MVO (1.34 [0.96-1.88]) groups. There were no differences in associations of alteplase dose or blood pressure lowering and outcomes across NVO/MVO/LVO groups (mRS shift: low versus standard alteplase dose 0.84 [0.54-1.30]/0.48 [0.25-0.91]/0.99 [0.75-2.09], Pinteraction = 0.28; intensive versus standard blood pressure lowering 1.32 [0.74-2.38]/0.78 [0.31-1.94]/1.24 [0.64-2.41], Pinteraction = 0.41), except for a borderline significant difference for intensive blood pressure lowering and increased early neurologic deterioration (0.63 [0.14-2.72]/0.17 [0.02-1.47]/2.69 [0.90-8.04], Pinteraction = 0.05). CONCLUSIONS: Functional outcome by dose of alteplase or intensity of blood pressure lowering is not modified by vascular obstruction status/site according to analyses from ENCHANTED, although these results are compromised by low statistical power.Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifiers: NCT01422616.

20.
Ecotoxicol Environ Saf ; 221: 112445, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34182199

RESUMO

Miscanthus sinensis is a C4 perennial grass species that is widely used as forage, ornamental grass and bioenergy crop due to its broad adaption and great biological traits. Recent studies indicated that M. sinensis could also grow in marginal lands which were contaminated with heavy metals, and exhibited important ecological restoration potential. In this study, transcriptome characterization of candidate genes related to chromium (Cr) uptake, transport and accumulation in M. sinensis were employed to investigate the molecular mechanism of plant tolerance to heavy metal stress. The result showed that following treatment of 200 mg/L of Cr, plant roots could accumulate most Cr and localize mainly in cell walls and soluble fractions, whereas Cr in stems and leaves was primarily in soluble fractions. A total of 83,645 differentially expressed genes (DEGs) were obtained after the treatment. Many genes involved in heavy metal transport, metal ion chelation and photosynthesis were found to be Cr-induced DEGs. Co-expression and weighted correlation network analysis revealed that Glutathion metabolism and ABC transporters pathways play an important role in Cr tolerance of M. sinensis. A hypothesis schematic diagram for the Cr uptake, transport and accumulation of M. sinensis cells were suggested, which could provide a molecular and genetic basis for future candidate genes validation and breeding of such crops.


Assuntos
Adaptação Fisiológica/genética , Cromo/metabolismo , Genes de Plantas/genética , Poaceae/genética , Poaceae/metabolismo , Transcriptoma/efeitos dos fármacos , Fenótipo , Fotossíntese , Melhoramento Vegetal , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Transcriptoma/genética
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