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1.
Life Sci ; 272: 119189, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33571516

RESUMO

AIMS: Acute pancreatitis (AP) is an inflammatory disease of the pancreas that may affect local tissues or remote organ systems, while severe acute pancreatitis (SAP) is a life-threatening disorder associated with multiple organ failure. In this investigation, we set about to determine whether microRNA-29a-3p (miR-29a-3p) carried by mesenchymal stem cell (MSCs)-derived extracellular vesicles (EVs) affects the myocardial injury during SAP. MAIN METHODS: EVs were isolated from MSCs of rat bone marrow by differential centrifugation. An SAP rat model was developed and treated with MSCs-EVs and/or alteration of miR-29a-3p and HMGB1 expression, followed by assessment of the rats' cardiac function and inflammation. Next, cardiomyocytes H9C2 were co-cultured with MSC-EVs and internalization of EVs was evaluated, followed by evaluation of whether EVs could transmit miR-29a-3p cargos into H9C2 cells and affect their biological functions. KEY FINDINGS: EVs derived from MSCs were observed to protect against SAP-induced myocardial injury. In SAP-induced rats, miR-29a-3p was under-expressed in myocardial tissues. In addition, we also confirmed that miR-29a-3p could be transferred into the H9C2 cardiomyocytes by MSC-derived EVs, which downregulated the expression of inflammatory markers and improve cardiac function to attenuate myocardial injury. Furthermore, miR-29a-3p inhibited the expression of HMGB1 to downregulate TLR4 expression and further inactivate the Akt signaling pathway. SIGNIFICANCE: These findings support the cardioprotective action of miR-29a-3p transmitted by MSCs-derived EVs in SAP-induced myocardial injury via downregulation of the HMGB1/TLR4/Akt axis, highlighting a promising target for the EV-based therapy for SAP.

2.
J Affect Disord ; 284: 120-125, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33592430

RESUMO

BACKGROUND: Sleep plays a key role in preserving cognitive function. However, the optimal strategies of sleep for cognition and the underlying mechanism are not well-established. METHODS: A cross-sectional study was performed using the China Health and Retirement Longitudinal Study (CHARLS), 2011-2012 survey. Self-reported nighttime sleep and afternoon napping data were collected. Fasting blood collected was analyzed for the high-sensitivity C-reactive protein (CRP) and white blood cell. RESULTS: Both nighttime sleep and afternoon napping were significantly associated with cognition after adjusting for confounders (p < 0.05). Precisely, participants with nighttime sleep of 6.1-7h had the highest cognition scores (p < 0.05). Participants with less than 30 min afternoon napping had the highest cognition scores (p < 0.05). The synergistic effect of nighttime sleep and afternoon napping was not significant (p > 0.05). Nighttime sleep and afternoon napping were significantly related to the white blood cell, but not the high-sensitivity CRP. The white blood cell mediated the association between sleep and cognition (p < 0.05). CONCLUSION: Nighttime sleep of six to seven hours and afternoon napping of less than 30 minutes are associated with optimal cognitive function in middle-aged and older people, respectively. Sleep influences cognition partly via the inflammatory profile.

3.
J Med Internet Res ; 23(2): e20298, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33625369

RESUMO

BACKGROUND: Identifying cognitive impairment early enough could support timely intervention that may hinder or delay the trajectory of cognitive impairment, thus increasing the chances for successful cognitive aging. OBJECTIVE: We aimed to build a prediction model based on machine learning for cognitive impairment among Chinese community-dwelling elderly people with normal cognition. METHODS: A prospective cohort of 6718 older people from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) register, followed between 2008 and 2011, was used to develop and validate the prediction model. Participants were included if they were aged 60 years or above, were community-dwelling elderly people, and had a cognitive Mini-Mental State Examination (MMSE) score ≥18. They were excluded if they were diagnosed with a severe disease (eg, cancer and dementia) or were living in institutions. Cognitive impairment was identified using the Chinese version of the MMSE. Several machine learning algorithms (random forest, XGBoost, naïve Bayes, and logistic regression) were used to assess the 3-year risk of developing cognitive impairment. Optimal cutoffs and adjusted parameters were explored in validation data, and the model was further evaluated in test data. A nomogram was established to vividly present the prediction model. RESULTS: The mean age of the participants was 80.4 years (SD 10.3 years), and 50.85% (3416/6718) were female. During a 3-year follow-up, 991 (14.8%) participants were identified with cognitive impairment. Among 45 features, the following four features were finally selected to develop the model: age, instrumental activities of daily living, marital status, and baseline cognitive function. The concordance index of the model constructed by logistic regression was 0.814 (95% CI 0.781-0.846). Older people with normal cognitive functioning having a nomogram score of less than 170 were considered to have a low 3-year risk of cognitive impairment, and those with a score of 170 or greater were considered to have a high 3-year risk of cognitive impairment. CONCLUSIONS: This simple and feasible cognitive impairment prediction model could identify community-dwelling elderly people at the greatest 3-year risk for cognitive impairment, which could help community nurses in the early identification of dementia.

4.
PLoS One ; 16(2): e0246166, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33529262

RESUMO

This study was to compare the efficacy and safety of combined glycoprotein IIb/IIIa inhibitor (GPI) and ticagrelor versus ticagrelor in patients with acute coronary syndrome (ACS). An observational study was conducted using the Improving Care for Cardiovascular Disease in China-ACS project. Totally, 13,264 patients with ACS and received combination therapy or ticagrelor therapy were analyzed. The primary outcome was the composite of major cardiovascular events (MACE: all-cause mortality, myocardial infarction [MI], stent thrombosis, cardiogenic shock, and ischemic stroke), and secondary outcomes included all-cause mortality, MI, stent thrombosis, cardiogenic shock, and ischemic stroke. The multivariable adjusted analysis indicated that combination therapy was associated with an increased risk of major cardiovascular events (MACE) (P = 0.001), any bleeding (P<0.001), and major bleeding (P = 0.005). Moreover, the multivariable adjusted for propensity score-matched (PSM) analysis suggested that combination therapy produced additional risk of MACE (P = 0.014), any bleeding (P<0.001), and major bleeding (P = 0.005). Moreover, PSM analysis suggested that combination therapy was associated with greater risk of stent thrombosis (P = 0.012) and intracranial bleeding (P = 0.020). Combined GPI and ticagrelor therapies did not have any beneficial effects on MACE, stent thrombosis, intracranial bleeding, any bleeding, or major bleeding.

5.
J Clin Oncol ; 39(7): 704-712, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33492986

RESUMO

PURPOSE: As yet, no checkpoint inhibitor has been approved to treat nasopharyngeal carcinoma (NPC). This study was aimed to evaluate the antitumor activity, safety, and biomarkers of toripalimab, a new programmed death-1 (PD-1) inhibitor for recurrent or metastatic NPC (RM-NPC) refractory to standard chemotherapy. PATIENTS AND METHODS: In this single-arm, multicenter phase II study, patients with RM-NPC received 3 mg/kg toripalimab once every 2 weeks via intravenous infusion until confirmed disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). The secondary end points included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS: Among all 190 patients, the ORR was 20.5% with median DOR 12.8 months, median PFS 1.9 months, and median OS 17.4 months. Among 92 patients who failed at least two lines of systemic chemotherapy, the ORR was 23.9%. The ORRs were 27.1% and 19.4% in PD-L1+ and PD-L1- patients, respectively (P = .31). Patients with ≥ 50% decrease of plasma Epstein-Barr virus (EBV) DNA copy number on day 28 had significantly better ORR than those with < 50% decrease, 48.3% versus 5.7% (P = .0001). Tumor mutational burden had a median value of 0.95 muts/mega-base in the cohort and had no predictive value for response. Whole-exome sequencing results from 174 patients revealed that the patients with genomic amplification in 11q13 region or ETV6 genomic alterations had poor responses to toripalimab. CONCLUSION: The POLARIS-02 study demonstrated a manageable safety profile and durable clinical response of toripalimab in patients with chemorefractory metastatic NPC. An early decrease in plasma EBV DNA copy number correlated with favorable response.

6.
Pest Manag Sci ; 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33423380

RESUMO

BACKGROUND: Antibacterial photocatalytic therapy has been employed as a promising strategy to combat antibiotic-resistant bacteria in the water disinfection field, especially some non-metal inorganic nanomaterials. However, their antibacterial activities on plant phytopathogens are poorly understood. Here, the photocatalytic antibacterial mechanism of the urea-synthesized graphitic carbon nitride nanosheets (g-C3 N4 nanosheets) against Pseudomonas syringae pv. tabaci was systematically investigated in vitro and in vivo. RESULTS: The g-C3 N4 nanosheets exhibited remarkable concentration-dependent and irradiation-time-dependent antibacterial properties, and the 0.5 mg mL-1 concentration ameliorated tobacco wildfire disease in host plants. Specifically, under visible irradiation, g-C3 N4 nanosheets produced numerous reactive oxygen species (ROS), supplementing the plentiful extracellular and intracellular ROS in bacteria. After exposing light-induced g-C3 N4 nanosheets for 1 h, 500 genes were differentially expressed, according to transcriptome analyses. Notably, the expression of genes related 'antioxidant activity' and 'membrane transport' was sharply upregulated, and those related to 'bacterial chemotaxis', 'biofilm formation', 'energy metabolism' and 'cell motility' were downregulated. After exposure for over 2 h, the longer-time pressure on the target bacteria cause the decreased biofilm formation and flagellum motility, further injuring the cell membranes leading to cytoplasm leakage and damaged DNA, eventually resulting in the bacterial death. Concomitantly, the attachment of g-C3 N4 nanosheets was a synergistic physical antibacterial pathway. The infection capacity assessment also supported the earlier supposition. CONCLUSION: These results provide novel insights into the photocatalytic antibacterial mechanisms of g-C3 N4 nanosheets at the transcriptome level, which are expected to be useful for dissecting the response pathways in antibacterial activities and for improving g-C3 N4 -based photocatalysts practices in plant disease control.

7.
PLoS Pathog ; 17(1): e1009220, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33476326

RESUMO

The eponymous member of the interferon regulatory factor (IRF) family, IRF1, was originally identified as a nuclear factor that binds and activates the promoters of type I interferon genes. However, subsequent studies using genetic knockouts or RNAi-mediated depletion of IRF1 provide a much broader view, linking IRF1 to a wide range of functions in protection against invading pathogens. Conserved throughout vertebrate evolution, IRF1 has been shown in recent years to mediate constitutive as well as inducible host defenses against a variety of viruses. Fine-tuning of these ancient IRF1-mediated host defenses, and countering strategies by pathogens to disarm IRF1, play crucial roles in pathogenesis and determining the outcome of infection.

8.
Ying Yong Sheng Tai Xue Bao ; 32(1): 39-45, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33477211

RESUMO

The aggravation of global nitrogen deposition may change plant water utilization and affect plant growth. Understanding the changes of vegetation water consumption under nitrogen deposition is of great significance for simulating and predicting the evolution of each component of forest hydrological cycle. We used the hydrogen and oxygen isotope tracer method to analyze water consumption source, quantity and law of Quercus mongolica (Qm), Fraxinus manshurica (Fm) and Tilia amurensis (Ta), the dominant species in broadleaved Korean pine forest of Changbai Mountain, under different add amounts of nitrogen [low nitrogen addition group (11.8 kg·hm-2·a-1), LN; high nitrogen addition group (23.6 kg·hm-2· a-1), HN] and different amounts of simulated precipitation (water addition amount were 0, 400, 800 and 1600 mL, equivalent to single rainfall amount were 0, 16, 32 and 64 mm, respectively). The results showed that under the condition of relative drought, soil water utilization ratio of Qm, Fm and Ta in the LN group were 26%, 12% and 20%, higher than that in HN group. When the amount of simulated precipitation was 16 mm, soil water utilization ratio of Qm, Fm and Ta in LN group reached the highest, being 73%, 70% and 43%, respectively. This ratio also reached a high value in HN group, but being less than the values in LN group. When the amount of simulated precipitation was 32 mm, soil water content approximated the average value in broadleaved Korean pine forest in the growing season in Changbai Mountain. The average soil water utilization ratio of test tree species in HN group was 39%, higher than that in LN group (16%). When the amount of simulated precipitation reached 64 mm, the soil water was saturation. Soil water utilization ratio of Qm, Fm and Ta in LN group was 14%, 5% and 1%, which was lower than that in HN group, the corresponding ratio were 64%, 13% and 10%, respectively. In conclusion, under the condition of less precipitation and relatively dry soil, the soil water utilization ratio of those three tree species were lower, and the increases of nitrogen availability further reduced the ratio. When the amount of precipitation was high and soil moisture was higher than the average value of the growing season, soil water utilization ratio of those tree species was higher. With the increases of soil nitrogen availability, this ratio was further increased.


Assuntos
Pinus , Água , China , Florestas , Nitrogênio/análise , República da Coreia , Solo , Árvores
9.
Sci Total Environ ; 768: 144517, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33454488

RESUMO

Phthalic acid esters (PAEs) are endocrine-disrupting compounds that are ubiquitous in surface water. However, early studies on PAEs only focused on six species on the priority contaminant list, and the seasonal variation in the PAE distribution in Taihu Lake, China is unclear. The present study investigated the occurrence, spatial distribution, and ecological risks of 16 PAEs in Taihu Lake during the dry, normal, and wet seasons. The results showed that dibutyl phthalate, diethylhexyl phthalate (DEHP), and diisobutyl phthalate (DIBP) were the major species detected in the surface water of Taihu Lake. The summed concentration of the six priority PAEs accounted for less than 50% of the total, indicating that the contamination of the other PAE congeners was non-negligible. Significant seasonal effects were observed that the total PAE concentration was higher in the wet season than in the dry season, and there were significant positive correlations between the total PAE concentration and rainfall, the water reserve, and the water level. In the dry season, a relatively high PAE level was detected in the area close to the inflow river estuary and the tourist island in the lake. The concentrations of PAEs in the lakeshore area were higher than those in the lake center in the normal season, and were generally high in the wet season. DEHP posed high risks for fish regardless of the season, while butyl benzyl phthalate, DIBP, dihexyl phthalate, and diphenyl phthalate also showed high risks in the normal and wet seasons. These results suggest that the contamination and risks of congeners other than the priority PAEs are also of necessary concern, and seasonal variation should be considered for a comprehensive understanding of PAE contamination in surface water.

10.
BMC Med Imaging ; 21(1): 13, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482750

RESUMO

BACKGROUND: Quantification of neovascularization changes in terms of neovascular complex (NVC) acquired from the optical coherence tomography angiography (OCTA) imaging is extremely important for diagnosis and treatment monitoring of proliferative diabetic retinopathy (PDR). However, only few vessel extraction methods have so far been reported to quantify neovascular changes in NVC with proliferative diabetic retinopathy PDR based on OCTA images. METHODS: Here we propose an optimized approach to segment blood vessels, which is based on an improved vascular connectivity analysis (VCA) algorithm and combined with morphological characterization and elimination of noise and artifacts. The length and width of vessels are obtained in the quantitative assessment of microvascular network. The feasibility of the proposed method is further studied by a treatment monitoring and statistical analysis process, as we have monitored and statistically analyzed the changes of NVC based on sampled OCTA images of PDR patients (N = 14) after treatment by intravitreal injection of conbercept. RESULTS: The proposed method has demonstrated better performance in accuracy compared with existing algorithms and can thus be used for PRD treatment monitoring. Following the PDR treatment monitoring study, our data has shown that from the 1st day to 7th day of treatment, the averaged (arithmetic mean) length of NVC has been substantially shortened by 36.8% (P < 0.01), indicating significant effects of treatment. Meanwhile, the averaged (arithmetic mean) width of NVC from the 1st day to 7th day of treatment has been increased by 10.2% (P < 0.05), indicating that most of the narrow neovascularization has been reduced. CONCLUSION: The results and analysis have confirmed that the proposed optimization process by the improved VCA method is both effective and feasible to segment and quantify the NVC with lower noise and fewer artifacts. Thus, it can be potentially applied to monitor the fibrovascular regression during the treatment period. Clinical Trial Registration This trial is registered with the Chinese Clinical Trial Registry (Registered 27 December 2017, http://www.chictr.org.cn , registration number ChiCTR-IPR-17014160).

11.
Biosensors (Basel) ; 11(1)2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33467122

RESUMO

In this paper, we developed an isolation system for A549 human lung carcinoma cells as an effective factor for the early diagnosis of lung cancer. A microfluidic immunomagnetic method was used, in which the combination of immunomagnetic separation and a microfluidic system allowed for increased isolation efficiency with uncomplicated manipulation. In the microfluidic immunomagnetic strategy, A549 cells were combined with aptamer-conjugated carboxylated magnetic beads and then collected in a specified region by applying a magnetic field. The results were recorded using a fluorescence microscope, and the captured targets were then quantified. The isolation efficiency of A549 cells is up to 77.8%. This paper developed a simple working procedure, which is less time consuming, high-throughput, and trustworthy for the isolation of A549 cells. This procedure can be a useful reference method for the development of an effective diagnosis and treatment method for lung cancer in the future.

12.
Trials ; 22(1): 27, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407773

RESUMO

BACKGROUND: Cognitive impairment is a common dysfunction after stroke that seriously affects the overall recovery of patients. Cognitive rehabilitation training is currently the main treatment to improve cognitive function, but its curative effect is limited. Acupuncture is a core component of traditional Chinese medicine (TCM), and some previous clinical studies have shown that it might be effective in treating post-stroke cognitive impairment (PSCI), but further evidence from large-sample studies is needed. The overall objective of this trial is to obtain further data to develop an optimized acupuncture treatment for PSCI by comparing the effects of different acupuncture treatment methods on cognitive function in PSCI patients. METHODS/DESIGN: In this multicenter, prospective, randomized controlled trial, 206 eligible stroke inpatients who meet the trial criteria will be randomly assigned to 2 groups: an electroacupuncture (EA) plus needle retention (NR) group and an EA group. Both groups of patients will undergo the same routine cognitive rehabilitation treatments. All treatments will be given 5 times per week for 8 weeks. The primary outcomes will be assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment scale (MOCA). The secondary outcome will be measured by the Barthel Index (BI). All outcomes will be evaluated at baseline, week 4, week 8, and the third and sixth month after the end of treatment. DISCUSSION: Our aim is to evaluate the effects of two different acupuncture treatment methods for treating PSCI patients. This study is expected to provide data to be used in developing an optimized acupuncture treatment method for PSCI treatment. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027849. Registered on 30 November 2019, http://www.chictr.org.cn/showproj.aspx?proj=46316.

13.
Chin J Integr Med ; 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33420583

RESUMO

OBJECTIVE: To study the effect of Tai Chi (TC) and resistance training (RT) with different intensity on the cancer-related fatigue (CRF) and quality of life (QoL) of middle-aged and elderly cancer patients. METHODS: Totally 120 cancer patients were enrolled and randomly assigned to 4 groups by a random number table, including TC group, high-intensity 60% one repetition maximum (1-RM) RT group (HIRT), low-intensity (30% 1-RM) RT group (LIRT) and control group, 30 patients in each group. Participants in the TC group received 24-form simplified Yang-style TC training at a frequency of 40 min per day, 3 days per week for 12 weeks. Patients in the two RT groups received 10 sessions, 6 designated movements per day, 3 days per week for 12 weeks. The 1-RM of 6 muscle groups, fat mass (FM), lean body mass (LBM), along with the scores of Brief Fatigue Inventory (BFI), QoL questionnaire for Chinese cancer patients receiving chemobiotherapy (QLQ-CCC), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9) and Pittsburgh Sleep Quality Index (PSQI) were measured before and after training. The adverse effect was also observed. RESULTS: After 12-week intervention, patients in both TC and RT groups showed significant improvements in CRF and QLQ-CCC compared to pre-treatment (P<0.05). Compared with the LIRT and TC groups, patients in the HIRT group improved more significantly in increasing muscle strength and LBM, and reducing in FM (P<0.05). Patients in the TC group significantly increased in lower limb muscle strength compared with the LIRT group (P<0.05). In addition, patients in the TC group showed more significant improvements in scores of GAD-7, PHQ-9 and PSQI than 2 RT groups (P<0.05). CONCLUSIONS: TC and RT, both low- and high-intensity training, can significantly increase muscle strength, reduce CRF and improve QoL in the middle-aged and elderly cancer patients. TC has a better effect than RT in terms of sleep quality and mental health. The long-term application is needed to substantiate the effect of TC as an alternative exercise in cancer patients.

14.
Magn Reson Imaging ; 75: 100-106, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33096226

RESUMO

OBJECTIVE: To test the performance of free-breathing Dynamic Contrast-Enhanced MRI (DCE-MRI) using a radial volumetric interpolated breath-hold examination (VIBE) sequence combined with diffusion-weighted imaging (DWI) for quantitative solitary pulmonary nodule (SPN) assessment. METHODS: A total of 67 SPN cases receiving routine MRI routine scans, DWI, and dynamic-enhanced MRI in our hospital from May 2017 to November 2018 were collected. These cases were divided into a malignant group and a benign group according to the characteristics of the SPNs. The quantitative DCE-MRI parameters (Ktrans, Kep, Ve) and apparent diffusion coefficient (ADC) values of the nodules were measured. RESULTS: The Ktrans and Kep values in the malignant group were higher than those in the benign group, while the ADC values in the malignant group were lower than those in the benign group. Furthermore, the Ktrans value of adenocarcinoma was higher than that of squamous cell carcinoma and small cell carcinoma (P < 0.05). The Ve value was significantly different between non-small cell carcinoma and small cell carcinoma (P < 0.05). With an ADC value of 0.98 × 10-3 mm2/s as the threshold, the specificity and sensitivity to diagnose benign and malignant nodules was 90.6% and 80%, respectively. CONCLUSION: High-temporal-resolution DCE-MRI using the r-VIBE technique in combination with DWI could contribute to pulmonary nodule analysis and possibly serve as a potential alternative to distinguish malignant from benign nodules as well as differentiate different types of malignancies.


Assuntos
Suspensão da Respiração , Imagem de Difusão por Ressonância Magnética , Processamento de Imagem Assistida por Computador , Nódulo Pulmonar Solitário/diagnóstico por imagem , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/fisiopatologia , Adulto , Idoso , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/fisiopatologia , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Nódulo Pulmonar Solitário/fisiopatologia
15.
J Matern Fetal Neonatal Med ; 34(3): 422-431, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30999786

RESUMO

Background: Macrosomia at birth is associated with maternal hyperglycemia and leads to subsequent susceptibility to obesity, abnormal glucose metabolism, hypertension, and dyslipidemia in offspring. Epigenetic reprogramming has been reported to be involved in the development of human diseases caused by suboptimal environmental or nutritional factors. The study was aiming to explore epigenetic mechanism influences on macrosomic infants exposed to intrauterine hyperglycemia. We performed a genome-wide analysis of DNA methylation in cord blood from macrosomic infants born to women with gestational diabetes in order to identify genes related to fetal growth or early adipose tissue development.Methods: To analyze the epigenetic patterns in umbilical cord blood in gestational diabetes mellitus (GDM), we collected umbilical cord blood from women with GDM (mean pregestational BMI of 24.4 kg/m2 and mean neonatal birth weight of 4366 g) and normal glucose-tolerant women (mean pregestational BMI of 19.8 kg/m2 and mean neonatal birth weight of 3166 g). Differentially methylated genes in the GDM group were identified using the Infinium HumanMethylation450 BeadChip array.Results: A total of 1251 genes were differentially methylated compared to the controls (p < .01). The methylation microarray data showed that two specific CpG sites (cg12604331 and cg08480098) in the gene body of ARHGEF11 were significantly hypomethylated in the cord blood in macrosomic infants. Altered DNA methylation levels of ARHGEF11 were negatively correlated with glucose levels and neonatal birth weight.Conclusions: Exposure to adverse intrauterine environments can alter fetal development, such as by affecting the nutritional status of the fetus. Such exposure can also result in significant epigenetic modifications, including DNA methylation, which could serve as a potential marker for nutrition and metabolic conditions at the neonatal stage or even in the adult.

16.
Huan Jing Ke Xue ; 42(1): 422-432, 2021 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-33372495

RESUMO

Biochar-based fertilizers can improve the mineralization of carbon and nitrogen in soil and enhance the soil micro-ecological environment due to particular physical and chemical properties. It is of great significance to explore the underlying mechanism of biochar-based fertilizer in the regulation of soil microorganisms and soil enzyme activity to improve soil quality. Field experiments were conducted to investigate the effects of different biochar-based fertilizer rates[0 (CK2), 0.6 (T1), 0.9 (T2), 1.2 (T3), and 1.5 (T4) t·hm-2]on soil nutrients, soil enzyme activity, and bacterial community structure. The results showed that with the application of biochar-based fertilizer, soil bulk density decreased, while the pH value, available P, available K, organic matter content, and the C/N ratio increased by 0.32%-5.83%, 14.09%-23.16%, 0%-38.70%, 7.49%-14.16%, and 4.06%-10.13%, respectively, compared to that of the CK2 treatment. With increasing rates of biochar-based fertilizer, the enzyme activity first increased and then decreased. Invertase (INV), urease (URE), catalase (CAT), and neutral phosphatase (NPH) activity under the application of biochar-based fertilizer were 63.73%-166.37%, 117.52%-174.03%, 12.98%-23.59%, and 60.84%-119.71% higher than that of CK2, respectively. The corresponding bacterial diversity was significantly improved, especially with regard to the increase in the abundance of growth promoting bacteria, such as Gemmatimonadetes and Proteobacteria, and decreased the abundance of Acidobacteria and Actinobacteria. The correlation analysis showed that soil C/N ratio was the key factor affecting soil enzyme activity, and there was a significant positive correlation between soil enzyme activity and bacterial diversity. There were significantly positive correlations among the activities of the above four soil enzymes and the relative abundance of Gemmatimonadetes (P<0.01), with CAT being the key factor affecting the bacterial community structure. This study revealed a relationship between soil enzyme activity and microbial colonies, which provides a theoretical basis and mechanism for applying biochar to regulate the soil enzyme and micro-ecological environment.


Assuntos
Microbiologia do Solo , Solo , Bactérias/genética , Carvão Vegetal , Fertilizantes
17.
BMC Plant Biol ; 20(1): 538, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33256588

RESUMO

BACKGROUND: Pistil development is a complicated process in plants, and female sterile mutants are ideal material for screening and cloning pistil development-related genes. Using the female sterile mutant (fsm1), BraA04g009730.3C was previously predicted as a candidate mutant gene encoding the STERILE APETALA (SAP) transcriptional regulator. In the current study, a parallel female sterile mutant (fsm2) was derived from EMS mutagenesis of a Chinese cabbage DH line 'FT' seeds. RESULTS: Both fsm2 and fsm1 mutant phenotypes exhibited pistil abortion and smaller floral organs. Genetic analysis indicated that the phenotype of mutant fsm2 was also controlled by a single recessive nuclear gene. Allelism testing showed that the mutated fsm1 and fsm2 genes were allelic. A single-nucleotide mutation (G-to-A) in the first exon of BraA04g009730.3C caused a missense mutation from GAA (glutamic acid) to GGA (glycine) in mutant fsm2 plants. Both allelic mutations of BraA04g009730.3C in fsm1 and fsm2 conferred the similar pistil abortion phenotype, which verified the SAP function in pistil development. To probe the mechanism of SAP-induced pistil abortion, we compared the mutant fsm1 and wild-type 'FT' pistil transcriptomes. Among the 3855 differentially expressed genes obtained, 29 were related to ovule development and 16 were related to organ size. CONCLUSION: Our study clarified the function of BraA04g009730.3C and revealed that it was responsible for ovule development and organ size. These results lay a foundation to elucidate the molecular mechanism of pistil development in Chinese cabbage.

18.
Aging (Albany NY) ; 122020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33288739

RESUMO

RhoA is a member of the RHO family GTPases and is associated with essential functions in gastric cancer. In this study, we identified a gastric cancer biomarker, termed the "regulation of RhoA activity panel" (RRAP). Patients with gastric cancer from The Cancer Genome Atlas database were divided into training (N=160) and validation (N=155) cohorts. A cohort of 109 Chinese gastric cancer patients was utilized as an independent validation. Patients with mutated RRAP showed significantly better overall survival than patients with wild type RRAP. We also analyzed the association between RRAP and the migration capacity, immune-related signatures, and the tumor microenvironment. RRAP-mutant tumors had a significantly lower degree of lymph node metastasis and lower activities of migration-related pathways. These tumors also showed significantly increased immune cell infiltration and cytotoxic activity. Furthermore, two independent patient cohorts who received immune checkpoint blockade therapy were assessed for RRAP mutant status. As expected, for both immunotherapy cohorts, higher response rates to immune checkpoint blockade therapy were observed in patients with RRAP-mutant tumors than in patients with wild type RRAP tumors. Overall, this study indicates that the RRAP gene set is a potential biomarker for gastric cancer prognosis and therapeutic selection.

20.
Drug Des Devel Ther ; 14: 5205-5215, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33268983

RESUMO

Purpose: Prodrug technology-based combination drug therapy has been exploited as a promising treatment strategy to achieve synergistic lung cancer therapy, reduce drug dose, and decrease side effects. In the present study, we synthesized a pH and glutathione (GSH) sensitive prodrug, cisplatin (CIS) and doxorubicin (DOX) conjugates (CIS-DOXp). CIS-DOXp was loaded by nanocarriers and delivered into the tumor site. Methods: pH and GSH sensitive CIS-DOX prodrug (CIS-DOXp) was synthesized by conjugating GSH responsive CIS prodrug with pH sensitive DOX prodrug. CIS-DOXp-loaded nanocarriers (CIS-DOXp NC) were prepared using emulsification and solvent evaporation method. The morphology, particle size, polydispersity index (PDI) and zeta potential of nanocarriers were measured. In vitro cytotoxicity of nanocarriers and the corresponding free drugs was examined using the MTT assay. In vivo anti-tumor efficiency and biodistribution behaviors were evaluated on lung cancer mice models. Results: The size, PDI, zeta potential, CIS loading efficiency, and DOX loading efficiency of CIS-DOXp NC were 128.6 ± 3.2 nm, 0.196 ± 0.021, 15.7 ± 1.7 mV, 92.1 ± 2.1%, and 90.4 ± 1.8%, respectively. The best cell killing ability (the lowest combination index of 0.57) was found at the combination ratio of 1:3 (CIS:DOX, w/w) in the drugs co-loaded formulations, indicating the strongest synergism effect. CIS-DOXp NC showed the best tumor inhibition efficiency (79.9%) in mice with negligible body weight lost. Conclusion: CIS-DOXp NC could be applied as a promising system for the synergistic chemotherapy of lung cancer.

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