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1.
BMC Pregnancy Childbirth ; 21(1): 610, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493234

RESUMO

BACKGROUND: We aimed to appraise the impact of the changing national childbirth policy since 2002, currently allowing two children per family, on obstetric workload in a regional referral center in China. METHODS: In a retrospective cohort study, temporal changes were examined in relation with maternal demographics, incidence of women with high risk pregnancies and resource statistics in our hospital in managing singleton viable pregnancies (birth from 28 weeks gestational age onwards) for the period 2005-2017. RESULTS: During this 13-year period, the number of singleton livebirths from 28 weeks gestational age onwards was 49,479. Annual numbers of births increased from 1,941 to 2005 to 5,777 in 2017. There were concomitant and significant increases in the incidence of multiparous women (10.6-50.8 %), of age ≥35 years (6.5-24.3 %), with prior caesarean Sec. (2.6-23.6 %), with ≥3 previous pregnancy terminations (1.0-4.9 %), with pre-gestational diabetes (0.2-0.9 %), and with chronic hypertension (0.2-1.2 %). There were associated increases in beds and staff complement and reduced average hospital stay. Nevertheless, while the workload of medical staff remained stable with increasing staff complement, that of midwives increased significantly as reflected by the total births: midwife ratio which increased from 194.1:1 to 320.9:1 (p < 0.001). CONCLUSIONS: In our hospital, progressively increasing numbers of annual births in combination with an increased incidence of women with high risk pregnancies took place following the revised national childbirth policy. Only the increase in medical and nursing, but not midwifery, staff was commensurate with workload. Remedial measures are urgently required before the anticipated progressive increase in care demand would overwhelm maternity care with potentially disastrous consequences.

2.
Bioresour Technol ; 341: 125807, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34474237

RESUMO

In recent years, visualization and characterization of lignocellulose at different scales elucidate the modifications of its ultrastructural and chemical features during hydrothermal pretreatment which include degradation and dissolving of hemicelluloses, swelling and partial hydrolysis of cellulose, melting and redepositing a part of lignin in the surface. As a result, cell walls are swollen, deformed and de-laminated from the adjacent layer, lead to a range of revealed droplets that appear on and within cell walls. Moreover, the certain extent morphological changes significantly promote the downstream processing steps, especially for enzymatic hydrolysis and anaerobic fermentation to bioethanol by increasing the contact area with enzymes. However, the formation of pseudo-lignin hinders the accessibility of cellulase to cellulose, which decreases the efficiency of enzymatic hydrolysis. This review is intended to bridge the gap between the microstructure studies and value-added applications of lignocellulose while inspiring more research prospects to enhance the hydrothermal pretreatment process.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34500402

RESUMO

Due to global outbreak of rice false smut disease, ustiloxin A (UA) was detected in rice. However, accurate methods for monitoring UA in human body fluids were lacking. In this context, a UPLC-MS/MS method based on two-step SPE was constructed for measuring UA in urine. The limits of UA quantification in human and mice urine were 58.3 and 108.7 ng/L, respectively. The proposed method was applied to detect UA in urine samples collected from human and mice. After dietary exposure, the contents of UA in mice urine were from 6.03 to 16.76 µg/g of creatine, accounting for approximate 14% of daily intake dose. Furthermore, due to the trace residues in rice (78-109 ng/kg), no detectable UA was observed in the urine of 20 volunteers. To the best of our knowledge, it is the first time to report the occurrence of UA in mammal urine.

4.
J Neurosci ; 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385360

RESUMO

Entorhinal cortex (EC) neurons make monosynaptic connections onto distal apical dendrites of CA1 and CA2 pyramidal neurons (PNs) through the perforant path (PP) projection. Previous studies show that differences in dendritic properties and synaptic input density enable the PP inputs to produce a much stronger excitation of CA2 compared to CA1 PNs. Here, using mice of both sexes, we report that the difference in PP efficacy varies substantially as a function of presynaptic firing rate. Although a single PP stimulus evokes a 5-6 fold greater EPSP in CA2 compared to CA1, a brief high-frequency train of PP stimuli evokes a strongly facilitating postsynaptic response in CA1, with relatively little change in CA2. Furthermore, we demonstrate that blockade of NMDARs significantly reduces strong temporal summation in CA1, but has little impact on that in CA2. As a result of the differences in the frequency- and NMDAR-dependent temporal summation, naturalistic patterns of presynaptic activity evoke CA1 and CA2 responses with distinct dynamics, differentially tuning CA1 and CA2 responses to bursts of presynaptic firing versus single presynaptic spikes, respectively.Significance StatementRecent studies have demonstrated abundant entorhinal cortical innervation and efficient dendritic propagation enable hippocampal CA2 pyramidal neurons to produce robust excitation evoked by single cortical stimuli, compared to CA1. Here we uncovered, unexpectedly, that the difference in efficacy of cortical excitation varies substantially as a function of presynaptic firing rate. A burst of stimuli evokes a strongly facilitating response in CA1, but not in CA2. As a result, postsynaptic response of CA1 and CA2 to presynaptic naturalistic firing displays contrasting temporal dynamics, which depends on the activation of NMDARs. Thus our findings provide a synaptic mechanism by which hippocampal neurons dynamically respond to irregular, high-frequency burst firing in entorhinal cortex in behaving animals.

5.
Medicine (Baltimore) ; 100(32): e26882, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397906

RESUMO

BACKGROUND: Papillary thyroid carcinoma (PTC) incidence has been increasing worldwide. Obesity, that is, having a high body mass index, is associated with the incidence of several cancers including colon, breast, esophageal, and kidney cancer. However, the association between obesity and the clinical features of PTC is still unknown. This study aimed to determine the impact of obesity on the clinical features of PTC. METHOD: A database search was conducted for articles published up to 2020 on obesity and clinical features of PTC. Data were extracted from articles that met the meta-analysis inclusion criteria. RESULTS: A total of 11 retrospective cohorts and 11,729 patients were included. Obesity was associated with the following variables in PTC patients: older age (difference in means = 1.95, 95% confidence interval [CI] 0.16-3.74, P = .03), male sex (odds ratio [OR] = 3.13, 95%CI 2.24-4.38, P < .00001), tumor size ≥1 cm (OR = 1.34, 95%CI 1.11-1.61, P < .002), multifocality (OR = 1.54, 95%CI 1.27-1.88, P < .0001), extrathyroidal extension (OR = 1.78, 95%CI 1.22-2.59, P = .003) and advanced tumor, node, metastasis stage (OR = 1.68, 95%CI 1.44-1.96, P < .00001). Preoperative serum thyroid-stimulating hormone level (difference in means  = 0.09, 95%CI 0.35-0.52, P = .70), Vascular invasion (OR = 0.84, 95%CI 0.56-1.26, P = .41), lymph node metastasis (OR = 1.07, 95%CI 0.87-1.32, P = .50), distant metastasis (OR = 1.14, 95%CI 0.64-2.04, P = .66), and recurrence (OR = 1.45, 95%CI 0.97-2.15, P = .07) were not associated with obesity. CONCLUSION: Obesity was associated with several poor clinicopathologic prognostic features: older age, male gender, tumor size ≥1 cm, extrathyroidal extension, multifocality, and advanced tumor/node/metastasis stage. However, thyroid-stimulating hormone level, vascular invasion, lymph node metastasis, distant metastasis, and recurrence were not associated with obesity in PTC.


Assuntos
Obesidade , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Índice de Massa Corporal , Causalidade , Progressão da Doença , Humanos , Obesidade/diagnóstico , Obesidade/epidemiologia , Prognóstico , Medição de Risco , Câncer Papilífero da Tireoide/epidemiologia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia
6.
Cancer Nurs ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34387235

RESUMO

BACKGROUND: Evidence shows that adolescent and young adult (AYA) cancer patients have an increasing survival rate but experience psychological distress and circadian rhythm dysregulation. Little is known about the effect of circadian rhythm on psychological distress. OBJECTIVE: To investigate the type of circadian rhythm in Chinese AYA cancer survivors and examine the associations among chronotype, demographic characteristics, psychological distress, anxiety and depression, character strengths, and medical coping in this group. METHODS: This cross-sectional study enrolled 800 AYA cancer participants, 728 of whom completed the Chinese version of the Morningness-Eveningness Questionnaire, the Distress Thermometer, the Hospital Anxiety and Depression Scale, the Three-Dimensional Inventory of Character Strengths, and the Medical Coping Modes Questionnaire. RESULTS: Evening- and morning-type participants accounted for 35.0% and 19.1%, respectively, among participants, which was significantly higher than those found in the general population. The prevalence of psychological distress was 84.9% among AYA cancer participants. Exercise, Distress Thermometer, and depression were important predictive factors for the circadian rhythm. CONCLUSIONS: Circadian rhythm disorder and psychological distress were common among AYA cancer survivors. Evening-type participants performed worse on character strength, confrontation, and avoidance of medical coping. IMPLICATIONS FOR PRACTICE: Healthcare professionals need to understand the circadian rhythm and psychological health of AYA cancer survivors. Psychological rehabilitation guidance, especially within the 6 months after diagnosis, may benefit AYA survivors according to their chronotype. Character strengths can also be used during rehabilitation to properly guide AYA survivors.

7.
Cancer Biol Med ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34459571

RESUMO

OBJECTIVE: Patients with non-small cell lung cancer (NSCLC) respond differently to cytokine-induced killer cell (CIK) treatment. Therefore, potential prognostic markers to identify patients who would benefit from CIK treatment must be elucidated. The current research aimed at identifying predictive prognostic markers for efficient CIK treatment of patients with NSCLC. METHODS: Patients histologically diagnosed with NSCLC were enrolled from the Tianjin Medical University Cancer Institute and Hospital. We performed whole-exome sequencing (WES) on the tumor tissues and paired adjacent benign tissues collected from 50 patients with NSCLC, and RNA-seq on tumor tissues of 17 patients with NSCLC before CIK immunotherapy treatment. Multivariate Cox proportional hazard regression analysis was used to analyze the association between clinical parameters and prognostic relevance. WES and RNA-seq data between lung squamous cell carcinoma (SCC) and adenocarcinoma (Aden) were analyzed and compared. RESULTS: The pathology subtype of lung cancer was the most significantly relevant clinical parameter associated with DFS, as analyzed by multivariate Cox proportional hazard regression (P = 0.031). The patients with lung SCC showed better CIK treatment efficacy and extended DFS after CIK treatment. Relatively low expression of HLA class II genes and checkpoint molecules, and less immunosuppressive immune cell infiltration were identified in the patients with lung SCC. CONCLUSIONS: Coordinated suppression of the expression of HLA class II genes and checkpoint molecules, as well as less immune suppressive cell infiltration together contributed to the better CIK treatment efficacy in lung SCC than lung Aden.

8.
Front Cell Infect Microbiol ; 11: 694395, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422680

RESUMO

Autoinducer-2 (AI-2) is believed to be a bacterial interspecies signaling molecule that plays an important role in the regulation of the physiological behaviors of bacteria. The effect of AI-2 on the process of necrotizing enterocolitis (NEC) is unknown, and the aim of this study was to study the effect of AI-2 in a mouse NEC model. C57BL/6 mouse pups were randomly divided into three groups: the control group, the NEC group, and the NEC+AI-2 (NA) group. Exogenous AI-2 (500 nM) was added to the formula milk of the NA group. The concentrations of fecal AI-2 and flora were tested. The expression of cytokines, TLR4 and NF-κB in intestinal tissue was detected. The AI-2 level was significantly decreased in the NEC group (P<0.05). Compared with the NEC group, the intestinal injury scores, expression of TLR4, NF-kB, and proinflammatory factors (IL-1ß, IL-6, IL-8 and TNF-α) were reduced, and expression of anti-inflammatory factor (IL-10) was increased in the NA group mice (P<0.05). At the phylum level, the Proteobacteria abundance in the NA group was significantly increased, while the Bacteroidota abundance in the control group was significantly increased (P<0.05). At the genus level, Helicobacter and Clostridium_sensu_stricto_1 exhibited significantly greater abundance in the NEC group than in the other two groups, while Lactobacillus had the opposite trend (P<0.05). In addition, the abundances of Klebsiella, Rodentibacter and Enterococcus were significantly higher in the NA group than in the NEC and control groups (P < 0.05). Exogenous AI-2 partially reverses flora disorder and decreases inflammation in an NEC mouse model.


Assuntos
Enterocolite Necrosante , Animais , Animais Recém-Nascidos , Disbiose , Enterocolite Necrosante/tratamento farmacológico , Inflamação/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL
9.
Dalton Trans ; 50(30): 10524-10532, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34259672

RESUMO

Nanomaterials, as carriers of small molecular drugs, have been a focal point in recent years. In this work, a carbazolyl functionalized metal-organic framework, UiO-67-CDC, was successfully synthesized employing the ligand 9H-carbazole-2,7-dicarboxylic acid (9H-2,7-CDC). Postsynthetic approaches targeted the cationization and replacement of the Lewis base carbazole site with two methyl groups, resulting in the positively charged skeleton, which has proven to be a promising carrier for the anticancer drug 5-fluorouracil (5-Fu). The prepared cationic framework UiO-67-CDC-(CH3)2 showed moderately high surface area, hierarchical pore structures, and positive surface characteristics, which effectively and selectivity encapsulated the electron-rich 5-Fu molecules through electrostatic attraction, with a relatively high loading of up to 56.5% (wt%). The drug delivery in simulated blood environment (pH = 7.4) exhibited a more effective release, demonstrating a physiological pH-responsive sustained release. Significantly, the electron-deficient Zr-MOF itself, as a kind of high-sensitivity fluorescence detector, has a unique fluorescence "turn-on" effect with 5-Fu. These results pave the way towards designing surface-engineered MOF materials of interest in drug delivery and fluorescent sensing applications.

10.
Thyroid ; 31(9): 1424-1435, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34269617

RESUMO

Background: Maternal thyroid hormone (TH) plays an essential role for fetal development, especially for the cardiovascular system and its central control. However, the precise consequences of altered TH action during the different periods in pregnancy remain poorly understood. Methods: To address this question, we used mice heterozygous for a mutant thyroid hormone receptor α1 (TRα1) and wild-type controls that were born to wild-type mothers treated with 3,3',5-triiodothyronine (T3) during the first or the second half of pregnancy. We then phenotyped the offspring animals as adults by in vivo measurements and postmortem tissue analyses. Results: Maternal T3 treatment in either half of the pregnancy did not affect postnatal growth development. Serum thyroxine and hypophyseal thyrotropin subunit beta or deiodinase type II expression was also not affected in any group, only TRα1 mutant males exhibited a reduction in serum T3 levels after the treatment. Likewise, hepatic deiodinase type I was not altered, but serum selenium levels were reduced by the maternal treatment in wild-type offspring of both genders. Most interestingly, a significant increase in heart weight was found in adult wild-types born to mothers that received T3 during the first or second half of pregnancy, while TRα1 mutant males were protected from this effect. Moreover, we detected a significant increase in heart rate selectively in male mice that were exposed to elevated maternal T3 in the second half of the pregnancy. Conclusion: Taken together, our findings demonstrate that maternal TH is of particular relevance during the second half of pregnancy for establishing cardiac properties, with specific effects depending on TRα1 or gender. The data advocate routinely monitoring TH levels during pregnancy to avoid adverse cardiac effects in the offspring.

11.
Cancer Med ; 10(18): 6416-6427, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34309232

RESUMO

Glioblastoma (GBM) is the most aggressive glioma, and is prone to develop resistance to chemotherapy and radiotherapy; hence, patients with glioblastoma have a high recurrence rate and a low 1-year survival rate. In addition, the pathogenesis of glioblastoma is complex and largely unknown, and the available treatments are limited. Here, we uncovered a fundamental role of DYRK1A in regulating NFATC1 in GBMs. We found that DYRK1A was highly expressed in glioma and glioblastoma cells, and its expression was positively correlated with that of NFATC1. Moreover, inhibition of DYRK1A promoted NFATC1 degradation in GBM cells and sharply reduced the transactivation of NFATC1, not only by decreasing the expression of NFATC1-targeted genes, but also by reducing the luciferase activity, and vice versa. However, DYRK1A had the opposite effect on NFATC2. Most importantly, our data suggest that DYRK1A inhibition reduces glioblastoma migration. Polypeptides derived from the DYRK1A-targeted motif of NFATC1, by competitively blocking DYRK1A kinase activity on NFATC1, clearly destabilized NFATC1 protein and impaired glioblastoma migration. We propose that the recovery of NFATC1 stability is a key oncogenic event in a large proportion of gliomas, and pharmacological inhibition of DYRK1A by polypeptides could represent a promising therapeutic intervention for GBM.

12.
Ying Yong Sheng Tai Xue Bao ; 32(6): 2129-2137, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34212619

RESUMO

The long-term series of geographic data and remote sensing data contain noise and perio-dic fluctuation. We used the improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN) to decompose the data of the normalized difference vegetation index (NDVI), precipitation, and temperature from 1982 to 2015 on per-pixels in the Loess Pla-teau to obtain residuals. Using the residual with less noise and periodic fluctuations, we examined the changes of NDVI and the relationship between NDVI and climatic factors. The results showed that the spatial change trend of NDVI was mainly increasing from 1982 to 2015 in the Loess Plateau. The significance of the change trend of residual NDVI (95.9%) was greater than the original NDVI (72.3%), with spatial variations. Temperature and precipitation could largely explain the changes in vegetation coverage. The proportions of areas with extremely significant positive and negative correlations between temperature and NDVI on the Loess Plateau were 83.7% and 13.9%, respectively, while that between precipitation and NDVI were 54.4% and 37.2%, respectively. There were obvious spatial variations in the responses of vegetation to climate change on the Loess Plateau. Different climatic factors had different effects on different types of vegetation. In general, temperature had stronger correlation with different vegetation than precipitation. Therefore, temperature was the main driving factor for the changes of vegetation cover in the Loess Plateau.


Assuntos
Mudança Climática , Ecossistema , China , Temperatura
13.
Mar Pollut Bull ; 170: 112651, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34217055

RESUMO

Marine sediments serve as a sink for contaminants of anthropogenic origin. Here, 25 major and trace elements were determined in surface and core sediments from an urban lagoon (Yundang Lagoon), China. The median concentrations of Pb, Cd, Cu, and Zn in both surface and core sediments exceeded global and crustal averages. Principal component analysis for the elements and ecological impact of the heavy metals indicated spatial heterogeneity in core sediments from different lagoon areas; however, no such pattern was observed in surface sediments. Geodetector analysis indicated spatial locations of lakes, pH, N%, C%, and S% as the major factors influencing the heterogeneity of potential ecological risk index, a cumulative measure of the ecological impact of heavy metal. The interaction detector indicated nonlinear and bivariate enhancement between different physicochemical parameters. Besides, a depth profile of the elements in different samples was also elucidated.


Assuntos
Metais Pesados , Oligoelementos , Poluentes Químicos da Água , China , Monitoramento Ambiental , Sedimentos Geológicos , Metais Pesados/análise , Medição de Risco , Poluentes Químicos da Água/análise
14.
Nutrients ; 13(6)2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34203015

RESUMO

The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (rs = -0.495), PCT (rs = -0.413), IL-6 (rs = -0.429), IL-1ß (rs = -0.440) and IL-10 (rs = -0.461). Positive associations were found for CD8+ T cells (rs = 0.636), NK cells (rs = 0.772), total IgG (rs = 0.493) and PaO2/FiO2 ratios (rs = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.


Assuntos
COVID-19/tratamento farmacológico , Estado Terminal/terapia , Deficiências Nutricionais/tratamento farmacológico , Suplementos Nutricionais , Micronutrientes/uso terapêutico , Selênio/uso terapêutico , Zinco/uso terapêutico , Idoso , Proteína C-Reativa/metabolismo , COVID-19/sangue , COVID-19/imunologia , Deficiências Nutricionais/complicações , Humanos , Sistema Imunitário/efeitos dos fármacos , Inflamação/sangue , Inflamação/tratamento farmacológico , Unidades de Terapia Intensiva , Interleucinas/sangue , Masculino , Micronutrientes/sangue , Micronutrientes/deficiência , Pessoa de Meia-Idade , Oxigênio/metabolismo , Síndrome do Desconforto Respiratório/tratamento farmacológico , Estudos Retrospectivos , SARS-CoV-2 , Selênio/sangue , Selênio/deficiência , Selenoproteína P/sangue , Índice de Gravidade de Doença , Zinco/sangue , Zinco/deficiência
15.
Se Pu ; 39(8): 827-834, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34212583

RESUMO

With rapid urbanization, increasing amounts of chemicals are being used in our daily life. Emerging organic contaminants are a large class of chemicals that are widely detected in the environment. They include pharmaceuticals and personal care products, pesticides, perfluorinated compounds, and endocrine-disrupting compounds. Recently, many countries have reported the occurrence of emerging organic contaminants. In addition, emerging organic contaminants are frequently detected in various environmental samples, including river and lake water samples. Despite their low concentrations in the environment, emerging organic contaminants are potential risks to humans and wildlife. Because they could lead to endocrine disrupting effects and the occurrence of resistance genes. Thus, the detection of emerging organic contaminants in the environment is imperative for ecological systems and human health. The recent development of analytical techniques has led to the identification of more emerging organic contaminants in the environment. At present, the commonly used chromatographic separation techniques include liquid chromatography and gas chromatography. For the identification and quantitation of emerging organic contaminants, chromatography is usually combined with spectroscopy or mass spectrometry. The concentrations of emerging organic contaminants are not sufficiently high to be detected directly, and the matrix is complex in environmental samples. Emerging organic contaminants also have diverse properties. Thus, environmental samples must be pretreated before detection. Pretreatment includes the concentration and purification of the environmental samples. The commonly used pretreatment methods are ultrasound-assisted extraction, QuEChERS, liquid-liquid extraction, and solid-phase extraction. With the development of pretreatment methods, solid-phase microextraction and stirred-bar adsorption extraction have also become popular. These sample pretreatment methods have many advantages such as good efficiency and effectivity for recycling target compounds. Hence, they are widely used. However, these methods are time-consuming, in addition to requiring expensive consumables and large amounts of organic solvents. Lyophilization is a technique used for product dehydration, preservation, and storage in the agricultural and food industries. It is also occasionally used to simplify the extraction procedure for drug residue analysis. There are three stages of lyophilization: freezing, primary drying, and secondary drying. Lyophilization has many advantages when used for pretreatment, namely, operational simplicity, less consumables, less sample volume, prolonged storage, and minimal sample loss. Lyophilization is thus an alternative method for the pretreatment of emerging organic contaminants in environmental samples. Recently, lyophilization has been applied to the pretreatment of emerging organic contaminants in environmental water samples. In general, a few steps were included during sample analysis. First, the samples were pretreated and frozen before the primary drying stage. After lyophilization, the analytes were extracted using a small amount of organic solvent and dried with nitrogen. Consequently, the elution was reconstructed and detected after dryness and filtration. Many groups of emerging organic contaminants could be recovered, including antibiotics, pesticides, and endocrine-disrupting compounds. The lyophilization could be automated, so that minimal manual intervention was required. By adopting lyophilization, good recoveries and accuracies were achieved. A few cleanup processes were conducted, and a small amount of organic solvent was consumed. Thus, lyophilization is a highly prospective pretreatment method for monitoring emerging organic contaminants, and can be extended to a diverse range of these contaminants. For large-scale and high-frequency sampling campaigns, cheap and convenient pretreatment is urgently needed. In this study, typical emerging organic contaminants are described, along with the universal types of such contaminants and the principles of lyophilization. The application of lyophilization to the detection of emerging organic contaminants in the environment is also introduced. The future of lyophilization is discussed, which provides a reference for emerging contaminant detection in environmental samples.


Assuntos
Liofilização , Poluentes Químicos da Água , Cromatografia Líquida , Cromatografia Gasosa-Espectrometria de Massas , Estudos Prospectivos , Extração em Fase Sólida , Poluentes Químicos da Água/análise
16.
Aging (Albany NY) ; 13(13): 17211-17226, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197336

RESUMO

Saxitoxin (STX), as a type of paralytic shellfish poisoning (PSP), is gaining widespread attention due to its long existence in edible shellfish. However, the mechanism underlying STX chronic exposure-induced effect is not well understood. Here, we evaluated the neurotoxicity effects of long-term low-dose STX exposure on C57/BL mice by behavioral tests, pathology analysis, and hippocampal proteomics analysis. Several behavioral tests showed that mice were in a cognitive deficiency after treated with 0, 0.5, 1.5, or 4.5 µg STX equivalents/kg body weight in the drinking water for 3 months. Compared with control mice, STX-exposed mice exhibited brain neuronal damage characterized by decreasing neuronal cells and thinner pyramidal cell layers in the hippocampal CA1 region. A total of 29 proteins were significantly altered in different STX dose groups. Bioinformatics analysis showed that protein phosphatase 1 (Ppp1c) and arylsulfatase A (Arsa) were involved in the hippo signaling pathway and sphingolipid metabolism pathway. The decreased expression of Arsa indicates that long-term low doses of STX exposure can cause neuronal inhibition, which is a process related to spatial memory impairment. Taken together, our study provides a new understanding of the molecular mechanisms of STX neurotoxicity.


Assuntos
Síndromes Neurotóxicas/patologia , Saxitoxina/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Região CA1 Hipocampal/patologia , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/psicologia , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/psicologia , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/patologia , Síndromes Neurotóxicas/psicologia , Proteômica , Células Piramidais/patologia
17.
Apoptosis ; 26(7-8): 474-487, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34212271

RESUMO

As a nucleic acid demethylase, Fat and obesity associated gene (FTO) plays a vital role in modulating adipose metabolism. However, it is still unknown how FTO affects apoptosis in adipocytes. In this study, we found that overexpression of FTO inhibited the expression of pro-apoptosis factors Caspase-3, Caspase-9 and Bax and mitochondrial unfolded protein response (UPRmt) markers HSP60 and ClpP in vivo and in vitro. Particularly, overexpression of FTO inhibited mitochondria-dependent apoptosis in adipocytes. Further studies revealed that FTO suppressed UPRmt by reducing HSP60 mRNA N6-methyladenosine (m6A) modification. Moreover, FTO inhibited the activation of Caspase-3 via JAK2/STAT3 signaling pathway in adipocytes. Further experiments showed that pro-apoptosis gene Bax was upregulated by UPRmt-activated PKR/eIF2α/ATF5 axis in adipocytes. In summary, this study confirms that FTO reduces adipocytes apoptosis by activiting JAK2/STAT3 signaling pathway and inhibiting UPRmt, revealing a novel mechanism of FTO on adipocytes apoptosis, which provides some new potential therapy for treating obesity and related metabolic syndromes.

18.
Blood ; 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34098582

RESUMO

We previously identified an association of rapid engraftment of patient-derived leukemia cells transplanted into NOD/SCID mice with early relapse in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In search for the cellular and molecular profiles associated with this phenotype, we investigated the expression of microRNAs (miRNAs) in different engraftment phenotypes and patient outcomes and found high miR-497/195 expression in patient-derived xenograft samples with slow engraftment, derived from patients with favorable outcome. In contrast, epigenetic repression and low expression of these miRNAs was observed in rapidly engrafting samples associated with early relapse. Overexpression of miR-497/195 in patient-derived leukemia cells suppressed in vivo growth of leukemia and prolonged recipient survival. Conversely, inhibition of miR-497/195 led to increased leukemia cell growth. Key cell cycle regulators were downregulated upon miR-497/195 overexpression and we identified CDK4/CCND3-mediated control of G1/S transition as a principal mechanism for the suppression of BCP-ALL progression by miR-497/195. The critical role for miR-497/195-mediated cell cycle regulation was underscored by the finding in an additional independent series of patient samples, showing that high miR-497/195 expression together with a full sequence of CDKN2A/B was associated with excellent outcome, while deletion of CDKN2A/B together with low expression of miR-497/195 was associated with clearly inferior relapse-free survival. These findings point to the cooperative loss of cell cycle regulators as new prognostic factor indicating possible therapeutic targets for pediatric BCP-ALL.

19.
Cancer Commun (Lond) ; 41(9): 889-903, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34184418

RESUMO

BACKGROUND: Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC). METHODS: Stage IIIB-IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4-6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127). RESULTS: Between December 15th , 2017, and May 15th , 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25th , 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1-6) and median duration of treatment of 3.0 (range 0.0-5.1) months. ORR of response-evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80-1.04, within the prespecified equivalence margin of 0.75-1.33). Up to May 15th , 2020, with a median follow-up of 13.6 (range 0.8-28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1-year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups. CONCLUSIONS: LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non-squamous NSCLC patients in the first-line setting.

20.
Int J Clin Pract ; 75(9): e14484, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34107151

RESUMO

OBJECTIVE: Autoimmune thyroid diseases, including Hashimoto's thyroiditis, are the most common ones among autoimmune diseases. The reported effects of selenium supplementation on the course of Hashimoto's thyroiditis are not consistent. It is therefore important to continue this line of research. DESIGN: The participants received selenium in the form of sodium selenite(IV) at a dose of 100 µg/day for 6 months. PATIENTS: Newly diagnosed and previously untreated Hashimoto's thyroiditis with euthyroidism or subclinical hypothyroidism. A total of 36 patients (aged 20 to 52 years) qualified for this study, of whom 29 women were successfully enrolled and completed the intervention. MEASUREMENTS: Both before and after supplementation the following parameters in serum were tested: anti-thyroid peroxidase antibodies, thyroid function indicators, selenium as well as antioxidant status parameters and other biochemical parameters (lipid profile, glucose). Iodine supply and subjective assessment of physical and psychological health were also monitored. RESULTS: Selenium supplementation decreased significantly level of anti-thyroid peroxidase antibodies what might have had a stabilizing effect on thyroid function, as values of thyroid parameters were within normal range before and at the end of the study. Mean level of selenium among patients was not different to healthy people in Poland. Median of ioduria was within normal range. CONCLUSIONS: The study shows a potential way of protective effect of selenium in limiting development of overt hypothyroidism. The increase in the concentrations of Se and SELENOP in the serum of patients verifies successful supplementation and good compliance, but did not affect the antioxidant status parameters measured.


Assuntos
Doença de Hashimoto , Hipotireoidismo , Selênio , Suplementos Nutricionais , Feminino , Doença de Hashimoto/tratamento farmacológico , Humanos , Hipotireoidismo/tratamento farmacológico
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