Publications by authors named "Lili Jiang"

365 Publications

Catalpol enhanced physical exercise-mediated brain functional improvement in post-traumatic stress disorder model via promoting adult hippocampal neurogenesis.

Aging (Albany NY) 2021 Jul 29;13(undefined). Epub 2021 Jul 29.

School of Life Science, Beijing Normal University, Beijing, China.

Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder characterized by hyper-response to environmental cues as well as the associated depressive and cognitive dysfunctions. According to the key roles of hippocampus for cognitive and emotional regulation, improving hippocampal functions, particularly hippocampal neural plasticity, is the necessary pathway to attenuate the core symptoms of PTSD. The effects of the alternative therapies such as exercise and natural compounds to reduce PTSD symptoms and promote adult hippocampal neurogenesis have been widely demonstrated. However, what is the effect of combining the exercise with traditional Chinese medical compounds remains unknown. In current study, we evaluated the effects of catalpol, which showed the pro-neurogenic effects in previous report, in regulating exercise-mediated PTSD therapeutic effects. With behavioral tests, we found that catalpol treatment promoted the effects of exercise to reduce the response of mice to dangerous cues, and simultaneously enhanced the antidepressant and cognitive protection effects. Moreover, by immunofluorescence we identified that catalpol promoted exercise-mediated hippocampal neurogenesis by enhancing the neural differentiation and mature neuronal survive. We further found that the promote effects of catalpol to exercise-induced environmental hyper-response, antidepressant effects and cognitive protective effects were all compromised by blocking neurogenesis with temozolomide (TMZ). This result indicates that hippocampal neurogenesis is prerequisite for catalpol to promote exercise-mediated brain functional improvement in PTSD model. In conclusion, our research identified the new function of natural compounds catalpol to promote the exercise-mediated brain functional changes in PTSD model, which depend on its effect promoting adult hippocampal neurogenesis.
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http://dx.doi.org/10.18632/aging.203313DOI Listing
July 2021

: A Systematic Review.

Front Oncol 2021 8;11:703949. Epub 2021 Jul 8.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

Objective: To evaluate the value of serum Human epididymis protein 4 (HE4) for predicting the resistance of ovarian cancer (OS) to platinum chemotherapy.

Method: We searched the MEDLINE (PubMed), EMBASE, Cochrane Central, Web of Science, SCOPUS, and CNKI databases and screened all studies evaluating serum HE4 for predicting OC resistance to treatment with platinum. Two researchers independently evaluated the quality of all eligible original studies using QUADAS-2. RevMan 5.4 was used to compile the quality evaluation form. We also performed a meta-analysis with STATA15.1, and Deek's funnel plots were used to detect any publication bias.

Results: Eight studies were included in the final meta-analysis. Our results showed that the sensitivity and specificity of preoperative serum HE4 in predicting the resistance of OC to platinum chemotherapy was 80% and 67%, respectively. The diagnostic odds ratio was 8, and the AUC was 0.78 (95% CI: 0.75-0.82), whereas the pooled sensitivity and specificity of serum HE4 after the third-cycle of chemotherapies for predicting chemoresistance in OC was 86% and 85%, respectively, with a diagnostic odds ratio of 33 and AUC = 0.92 (95% CI: 0.89 - 0.94).

Conclusion: HE4 may be an effective predictor of platinum-based chemotherapeutic resistance of OC. Serum HE4 levels after the third chemotherapy cycle may be indicative for clinical practice. Further research is needed to validate the significance of HE4 in the long-term management of OC.

Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42021220099).
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http://dx.doi.org/10.3389/fonc.2021.703949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295753PMC
July 2021

Assessing the applications of transitional care and its impact on the quality of life in patients after total laryngectomy.

Am J Transl Res 2021 15;13(6):7349-7355. Epub 2021 Jun 15.

Department of Oral Surgery Department, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200011, China.

Objective: To explore the effect of transitional care and its impact on quality of life (QoL) in patients who underwent total laryngectomy.

Methods: The study enrolled 68 patients who were admitted to our hospital and underwent total laryngectomy from January 2017 to January 2019. The subjects were randomly divided into an observation group and a control group. Conventional care was given to the control group (34 cases), while conventional and transitional care was given to the observation group (34 cases). The study sought to compare the self-care ability, health knowledge, satisfaction with nursing, and QoL between the two groups at discharge and 6 months after discharge.

Result: Compared with the control group, the observation group showed higher scores in self-care ability, more extensive health knowledge, greater satisfaction, and better QoL at 6 months after discharge from the hospital. The differences were statistically significant (P < 0.05).

Conclusion: Transitional care can effectively improve the following performance in patients, including self-care activity after hospital discharge, health knowledge, and satisfaction with care, medication adherence, and QoL. Transitional care can be considered in a broader application.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290806PMC
June 2021

Comparison of Hepatotoxicity Associated With New BCR-ABL Tyrosine Kinase Inhibitors vs Imatinib Among Patients With Chronic Myeloid Leukemia: A Systematic Review and Meta-analysis.

JAMA Netw Open 2021 Jul 1;4(7):e2120165. Epub 2021 Jul 1.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China.

Importance: Although BCR-ABL fusion oncoprotein tyrosine kinase inhibitors (BCR-ABL TKIs) can substantially improve the survival rate of chronic myeloid leukemia (CML), they are clinically accompanied by severe hepatotoxicity.

Objective: To compare the relative risk (RR) of hepatotoxicity of new-generation BCR-ABL TKIs with that of imatinib, and to provide an overall assessment of the clinical benefit.

Data Sources: PubMed, Embase, Cochrane library databases, and ClinicalTrials.gov were searched for clinical trials published between January 2000 and April 2020.

Study Selection: Study selection was conducted independently by 2 investigators according to the inclusion and exclusion criteria published previously in the protocol: only randomized phase 2 or phase 3 clinical trials that compared bosutinib, dasatinib, nilotinib, or ponatinib with imatinib were included. Among the 2666 records identified, 9 studies finally fulfilled the established criteria.

Data Extraction And Synthesis: Two investigators extracted study characteristics and data independently using a standardized data extraction form. Data were extracted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. When substantial heterogeneity was observed, pooled estimates were calculated based on the random-effect model; otherwise, the fixed-effect model was used.

Main Outcomes And Measures: Data extracted included study characteristics, baseline patient information, interventions and data on all-grade and high-grade (grades 3 and 4) elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, overall survival, and major molecular response (MMR). The RRs and 95% CIs were calculated using the inverse variance method.

Results: Nine trials involving 3475 patients were analyzed; the median (range) age was 49 (18-91) years; 2059 (59.2%) were male patients. Increased risks were observed for each new-generation TKI except for dasatinib. Patients receiving new-generation TKIs were more likely to experience all grades of ALT elevation (pooled RR, 2.89; 95% CI, 1.78-4.69; P < .001) and grades 3 and 4 ALT elevation (pooled RR, 4.36; 95% CI, 2.00-9.50; P < .001) compared with those receiving imatinib. Patients receiving new-generation TKIs were also more likely to experience all grades of AST elevation (pooled RR, 2.20; 95% CI, 1.63-2.98; P < .001) and grades 3 and 4 AST elevation (pooled RR, 2.65; 95% CI, 1.59-4.42; P < .001) compared with those receiving imatinib. New-generation TKIs were associated with a significantly higher rate of MMR at 1 year compared with imatinib (pooled RR, 1.59; 95% CI, 1.44-1.75; P < .001). No statistical difference in overall survival at 1 year was found between new-generation TKIs and imatinib (pooled RR, 1.00; 95% CI, 1.00-1.01; P = .33).

Conclusions And Relevance: When compared to imatinib, bosutinib, nilotinib, and ponatinib had higher relative risks of hepatotoxicity. Treatment with new-generation TKIs was associated with a higher MMR rate at 1 year but not with 1-year overall survival.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.20165DOI Listing
July 2021

Efficacy and safety of levetiracetam versus (fos)phenytoin for second-line treatment of epilepticus: a meta-analysis of latest randomized controlled trials.

Seizure 2021 Jul 13;91:339-345. Epub 2021 Jul 13.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin 124221, China. Electronic address:

Objectives: To assess the efficiency and safety profiles of levetiracetam and (fos)phenytoin (phenytoin or fosphenytoin) for second-line treatment of seizures by performing a meta-analysis of RCTs.

Methods: We systematically searched PubMed, Embase, Cochrane, FDA.gov, and ClinicalTrials.gov for RCTs (published before July 31, 2020; no language restrictions). Two independent reviewers screened abstracts and titles against inclusion and exclusion criteria published previously in the PROSPERO: CRD42020202736. Eleven studies fulfilled the established criteria. We assessed pooled data by using a random-effects model. Quality analysis was performed by using version 2 of the Cochrane risk-of-bias tool (RoB 2). RevMan v.5.3 was used to perform statistical analyses, and publication bias (egger's test) was assessed with Stata MP v.14.0.

Results: Levetiracetam was similar to (fos)phenytoin in seizure termination rate (risk ratio [RR] 0.94; 95% CI 0.87 to 1.01), time of seizure termination (mean difference [MD] 0.44; -0.60 to 1.49), and drug resistance ([RR] 1.12, 0.86 to 1.45). The safety outcome showed a significant statistical difference between fosphenytoin group and levetiracetam group ([RR] 1.44, 1.14 to 1.81), while there was no significant difference observed between phenytoin treatment and levetiracetam treatment ([RR] 1.26, 0.99 to 1.60).

Conclusion: Levetiracetam was similar to (fos)phenytoin in cessation rate convulsive status epilepticus, and drug resistance, while it was superior (fos)phenytoin in pooled safety outcome. Further exploration is still needed as to whether it is the first choice for second-line drugs.
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http://dx.doi.org/10.1016/j.seizure.2021.07.012DOI Listing
July 2021

Comparison of 2940 nm Er: YAG laser treatment in the microlaser peel, fractional ablative laser, or combined modes for the treatment of concave acne scars.

Medicine (Baltimore) 2021 Jul;100(28):e26642

The Department of Plastic and Cosmetic Surgery.

Objective: To compare and analyze the effects of Er:YAG laser treatment in the microlaser peeling, fractional ablative laser, or combined modes for the treatment of concave acne scars.

Method: Ninety patients of concavity acne scar were randomly assigned to three different groups:microlaserpeeling mode group (MM group), fractional ablative mode group (FM group) and combined mode group (CM group). MM group received microlaserpeeling mode with depth of 60 μm and a repetition rate of 20%, FM group received fractional ablative mode with depth of 300 μm and a fractional density of 8%, and CM group received a fractional depth of 200 μm, density of 8%, and a peeling depth of 30 μm, repetition rate of 20%. All patients were evaluated for their treatment effects and side effects 30 days after treatment, including the treatment satisfaction, the ECCA grading scale, pain score and pigmentation level.

Results: According to the effect satisfaction of patients' self-assessment, the difference among the three groups was statistically significant (P < .05), the CM group was better than the other two groups, but there was no significant difference between the FM group and the MM group (P > .05). About the ECCA grading scale 30 days after treatment, the statistical result among the three groups was significant (P < .05), the CM group is much lower than the FM group which is approximately equal to the MM group. There was statistical difference in pain score among the three groups and every two groups (P < .05), the CM group had the highest pain score, while FM group had the lowest. About the pigmentation level, there was statistical difference among the three groups (P < .05), FM group had the lightest pigmentation, while the CM group had the heaviest.

Conclusions: Three treatment modes are all effective in treating the concavity acne scar. Among the three modes, CM group is best effective, also accompanied with the most severe side effect; FM group achieves the best balance between treatment effect and side effect. The treatment practices indicate that when the Er:YAG laser with a wavelength of 2940 nm is used to treat concavity acne scars, the right treatment mode should be subject to the severity of the scar.
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http://dx.doi.org/10.1097/MD.0000000000026642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284722PMC
July 2021

Ambient climate determines the directional trend of community stability under warming and grazing.

Glob Chang Biol 2021 Jul 6. Epub 2021 Jul 6.

Key Laboratory of Adaptation and Evolution of Plateau Biotac, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China.

Changes in ecological processes over time in ambient treatments are often larger than the responses to manipulative treatments in climate change experiments. However, the impacts of human-driven environmental changes on the stability of natural grasslands have been typically assessed by comparing differences between manipulative plots and reference plots. Little is known about whether or how ambient climate regulates the effects of manipulative treatments and their underlying mechanisms. We collected two datasets, one a 36-year long-term observational dataset from 1983 to 2018, and the other a 10-year manipulative asymmetric warming and grazing experiment using infrared heaters with moderate grazing from 2006 to 2015 in an alpine meadow on the Tibetan Plateau. The 36-year observational dataset shows that there was a nonlinear response of community stability to ambient temperature with a positive relationship between them due to an increase in ambient temperature in the first 25 years and then a decrease in ambient temperature thereafter. Warming and grazing decreased community stability with experiment duration through an increase in legume cover and a decrease in species asynchrony, which was due to the decreasing background temperature through time during the 10-year experiment period. Moreover, the temperature sensitivity of community stability was higher under the ambient treatment than under the manipulative treatments. Therefore, our results suggested that ambient climate may control the directional trend of community stability while manipulative treatments may determine the temperature sensitivity of the response of community stability to climate relative to the ambient treatment. Our study emphasizes the importance of the context dependency of the response of community stability to human-driven environmental changes.
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http://dx.doi.org/10.1111/gcb.15786DOI Listing
July 2021

Ultrasensitive electrochemical detection of microRNA based on in-situ catalytic hairpin assembly actuated DNA tetrahedral interfacial probes.

Talanta 2021 Oct 10;233:122600. Epub 2021 Jun 10.

MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350116, People's Republic of China. Electronic address:

Selective and sensitive detection of microRNA is crucial for early diagnosis and pathogenesis of disease. Here, we established a novel electrochemical biosensor for simple and accurate analysis of the tumor biomarker microRNA-141, which was based on in-situ catalytic hairpin assembly (CHA) actuated DNA tetrahedral (DTN) interfacial probes. Two hairpin structures used for CHA reaction were placed on the DTN, in which the hairpin H1 on the one vertex of DTN and hairpin H2 embedded in adjacent edge, respective. The target microRNA-141 could open the hairpin H1 and activated the in-situ CHA reaction between H1 and H2 to alter the conformational of DTN, increasing the chances of the direct interaction between methylene blue (MB) and the electrode surface, leading to an increase in the electrochemical signal. Meanwhile, the released miRNA-141 could unfold another H1, enabling the enzyme-free recycling of the target to obtain amplified electrochemical signals. Moreover, the in-situ catalytic hairpin assembly reaction on DTN could shorten the reaction time and enhance the sensitivity. The established biosensor exhibited a wide linear dynamic range of miRNA-141 from 1 fM to 100 pM with a detection limit of 0.32 fM. Besides, the approach can discriminate the target miRNA from mismatched ones with excellent selectivity and can be successfully applied in diluted serum samples, holding great potential for sensitive detection of various biomarkers clinically.
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http://dx.doi.org/10.1016/j.talanta.2021.122600DOI Listing
October 2021

Inhibition of human UDP-glucuronosyltransferase enzyme by Dabrafenib: Implications for drug-drug interactions.

Biomed Chromatogr 2021 Jun 30:e5205. Epub 2021 Jun 30.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China.

Dabrafenib is a novel small molecule tyrosine kinase inhibitor (TKI) which is used to treat metastatic melanoma. The aim of this research was to survey the effects of dabrafenib on human UDP-glucuronosyltransferases (UGTs) and to evaluate the risk of drug-drug interactions (DDIs). The formation rates for 4-methylumbelliferone (4-MU) glucuronide and trifluoperazine-glucuronide in 12 recombinant human UGT isoforms with or without dabrafenib were measured and HPLC was used to investigate the inhibitory effects of dabrafenib on UGTs. Inhibition kinetic studies were also conducted. In vitro-in vivo extrapolation approaches were further used to predict the risk of DDI potentials of dabrafenib via inhibition of UGTs. Our data indicated that dabrafenib had a broad inhibitory effect on 4-MU glucuronidation by inhibiting the activities of UGTs, especially on UGT1A1, UGT1A7, UGT1A8, and UGT1A9, and dabrafenib could increase the area under the curve of co-administered drugs. Dabrafenib is a strong inhibitor of several UGTs and the co-administration of dabrafenib with drugs primarily metabolized by UGT1A1, 1A7, 1A8 or 1A9 may induce potential DDIs.
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http://dx.doi.org/10.1002/bmc.5205DOI Listing
June 2021

Multiple imputation of maritime search and rescue data at multiple missing patterns.

PLoS One 2021 18;16(6):e0252129. Epub 2021 Jun 18.

China Waterborne Transport Research Institute, Beijing, PR China.

Based on the missing situation and actual needs of maritime search and rescue data, multiple imputation methods were used to construct complete data sets under different missing patterns. Probability density curves and overimputation diagnostics were used to explore the effects of multiple imputation. The results showed that the Data Augmentation (DA) algorithm had the characteristics of high operation efficiency and good imputation effect, but the algorithm was not suitable for data imputation when there was a high data missing rate. The EMB algorithm effectively restored the distribution of datasets with different data missing rates, and was less affected by the missing position; the EMB algorithm could obtain a good imputation effect even when there was a high data missing rate. Overimputation diagnostics could not only reflect the data imputation effect, but also show the correlation between different datasets, which was of great importance for deep data mining and imputation effect improvement. The Expectation-Maximization with Bootstrap (EMB) algorithm had a poor estimation effect on extreme data and failed to reflect the dataset's variability characteristics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252129PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213137PMC
June 2021

Knocking out c-Jun promotes cardiomyocyte differentiation from embryonic stem cells.

Int J Cardiol 2021 Jun 14. Epub 2021 Jun 14.

Department of Cardiovascular Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China. Electronic address:

Background: Morbidity and mortality associated with cardiovascular diseases, such as myocardial infarction, stem from the inability of terminally differentiated cardiomyocytes to regenerate, and thus repair the damaged myocardial tissue structure. The molecular biological mechanisms behind the lack of regenerative capacity for those cardiomyocytes remains to be fully elucidated. Recent studies have shown that c-Jun serves as a cell cycle regulator for somatic cell fates, playing a key role in multiple molecular pathways, including the inhibition of cellular reprogramming, promoting angiogenesis, and aggravation of cardiac hypertrophy, but its role in cardiac development is largely unknown. This study aims to delineate the role of c-Jun in promoting early-stage cardiac differentiation.

Methods: The c-Jun gene in mouse embryonic stem cells (mESCs) was knocked out with CRISPR-Cas9, and the hanging drop method used to prepare the resulting embryoid bodies. Cardiac differentiation was evaluated up to 9 days after c-Jun knockout (ko) via immunofluorescence, flow cytometric, and qPCR analyses.

Results: Compared to the wild-type control group, obvious beating was observed among the c-Jun-ko mESCs after 6 days, which was also associated with significant increases in myocardial marker expression. Additionally, markers associated with mesoderm and endoderm cell layer development, essential for further differentiation of ESCs into cardiomyocytes, were also up-regulated in the c-Jun-ko cell group.

Conclusions: Knocking out c-Jun directs ESCs towards a meso-endodermal cell lineage fate, in turn leading to generation of beating myocardial cells. Thus, c-Jun plays an important role in regulating early cardiac cell development.
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http://dx.doi.org/10.1016/j.ijcard.2021.06.017DOI Listing
June 2021

Analysis of expression characteristics of soybean leaf and root tissue-specific promoters in Arabidopsis and soybean.

Transgenic Res 2021 Jun 11. Epub 2021 Jun 11.

Jilin Provincial Key Laboratory of Agricultural Biotechnology, Jilin Academy of Agricultural Sciences, 130033, Changchun, China.

The characterization of tissue-specific promoters is critical for studying the functions of genes in a given tissue/organ. To study tissue-specific promoters in soybean, we screened tissue-specific expressed genes using published soybean RNA-Seq-based transcriptome data coupled with RT-PCR analysis. We cloned the promoters of three genes, GmADR1, GmBTP1, and GmGER1, and constructed their corresponding β-Glucuronidase (GUS) promoter-GUS reporter vectors. We generated transgenic Arabidopsis plants and examined the expression patterns of these promoters by GUS staining and RT-PCR analysis. We also transformed the promoter-GUS reporter vectors into soybean to obtain hairy roots, and examined promoter expression by GUS staining. We found a root-specific expression pattern of GmADR1 and GmBTP1 in both Arabidopsis and soybean, and the promoter of GmGER1 showed a leaf-specific pattern in transgenic Arabidopsis plants. To test the potential utility of these promoters in soybean improvement by transgenic means, we used the GmADR1 promoter to drive expression of a salt resistance gene in soybean, GmCaM4, by generating transgenic soybean plants. We found that the transgenic plants had significantly enhanced salt tolerance compared to non-transformed wild-type, suggesting that introducing endogenous promoters by transgenic means can drive the expression of functional genes in specific tissues and organs in soybean.
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http://dx.doi.org/10.1007/s11248-021-00266-7DOI Listing
June 2021

A machine learning framework to improve effluent quality control in wastewater treatment plants.

Sci Total Environ 2021 Aug 16;784:147138. Epub 2021 Apr 16.

Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden. Electronic address:

Due to the intrinsic complexity of wastewater treatment plant (WWTP) processes, it is always challenging to respond promptly and appropriately to the dynamic process conditions in order to ensure the quality of the effluent, especially when operational cost is a major concern. Machine Learning (ML) methods have therefore been used to model WWTP processes in order to avoid various shortcomings of conventional mechanistic models. However, to the best of the authors' knowledge, no ML applications have focused on investigating how operational factors can affect effluent quality. Additionally, the time lags between process steps have always been neglected, making it difficult to explain the relationships between operational factors and effluent quality. Therefore, this paper presents a novel ML-based framework designed to improve effluent quality control in WWTPs by clarifying the relationships between operational variables and effluent parameters. The framework consists of Random Forest (RF) models, Deep Neural Network (DNN) models, Variable Importance Measure (VIM) analyses, and Partial Dependence Plot (PDP) analyses, and uses a novel approach to account for the impact of time lags between processes. Details of the framework are provided along with a demonstration of its practical applicability based on a case study of the Umeå WWTP in Sweden involving a large number of samples (105763) representing the full scale of the plant's operations. Two effluent parameters, Total Suspended Solids in effluent (TSS) and Phosphate in effluent (PO4), and thirty-two operational variables are studied. RF models are developed, validated using DNN models as references, and shown to be suitable for VIM and PDP analyses. VIM identifies the variables that most strongly influence TSS and PO4, while PDP elucidates their specific effects on TSS and PO4. The major findings are: (1) Influent temperature is the most influential variable for both TSS and PO4, but it affects them in different ways; (2) PO4 depends strongly on the TSS in aeration basins - higher TSS concentrations in aeration basins generally promote PO removal, but excess TSS can have negative effects; (3) In general, the impact of TSS in aeration basins on TSS and PO4 increases with the distances of the basin from the merging outlet, so more attention should be paid to the TSS concentration in the third or fourth aeration basins than the first and second ones; (4) Returning excessive amounts of sludge through the second return sludge pipe should be avoided because of its adverse impact on TSS removal. These results could support the development of more advanced control strategies to increase control precision and reduce running costs in the Umeå WWTP and other similarly configured WWTPs. The framework could also be applied to other parameters in WWTPs and industrial processes in general if sufficient high-resolution data are available.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147138DOI Listing
August 2021

The Influence of Air Pollutants and Meteorological Conditions on the Hospitalization for Respiratory Diseases in Shenzhen City, China.

Int J Environ Res Public Health 2021 05 12;18(10). Epub 2021 May 12.

National Key Laboratory of Resources and Environmental Information System, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing 100101, China.

Air pollutants have significant direct and indirect adverse effects on public health. To explore the relationship between air pollutants and meteorological conditions on the hospitalization for respiratory diseases, we collected a whole year of daily major air pollutants' concentrations from Shenzhen city in 2013, including Particulate Matter (PM, PM), Nitrogen dioxide (NO), Ozone (O), Sulphur dioxide (SO), and Carbon monoxide (CO). Meanwhile, we also gained meteorological data. This study collected 109,927 patients cases with diseases of the respiratory system from 98 hospitals. We investigated the influence of meteorological factors on air pollution by Spearman correlation analysis. Then, we tested the short-term correlation between significant air pollutants and respiratory diseases' hospitalization by Distributed Lag Non-linear Model (DLNM). There was a significant negative correlation between the north wind and NO and a significant negative correlation between the south wind and six pollutants. Except for CO, other air pollutants were significantly correlated with the number of hospitalized patients during the lag period. Most of the pollutants reached maximum Relative Risk (RR) with a lag of five days. When the time lag was five days, the annual average of PM, PM, SO, NO, and O increased by 10%, and the risk of hospitalization for the respiratory system increased by 0.29%, 0.23%, 0.22%, 0.25%, and 0.22%, respectively. All the pollutants except CO impact the respiratory system's hospitalization in a short period, and PM10 has the most significant impact. The results are helpful for pollution control from a public health perspective.
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http://dx.doi.org/10.3390/ijerph18105120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151817PMC
May 2021

Recent research progress on the role of ulinastatin in chronic kidney disease.

Nephrology (Carlton) 2021 May 28. Epub 2021 May 28.

The First Hospital of Jilin University, Changchun, Jilin, China.

With the continuous improvement in living standards, lifestyle changes and ageing of the population, the prevalence of chronic kidney disease (CKD) has increased significantly, and its prevention and treatment have become important public health issues worldwide. Renal fibrosis is the main pathological basis of CKD progression to end-stage renal disease. Preventing the progression of renal fibrosis has always been the focus of clinical and scientific research. Ulinastatin is a serine protease inhibitor that is found in human blood and urine and inhibits the inflammatory response, regulates immunity and improves the microcirculation. It is widely used in patients with sepsis and septic shock in clinical practice. Recent studies have shown that ulinastatin can also play an important anti-fibrotic and organ protective role and can provide a new therapeutic hope for CKD patients. This review mainly introduced the research progress of UTI in inflammation, oxidative stress, apoptosis, acute kidney injury and renal fibrosis. By investigating the role of ulinastatin in CKD, we can determine the possible mechanisms for its renal protection and improvement of renal fibrosis, so as to provide new ideas for the treatment of CKD.
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http://dx.doi.org/10.1111/nep.13906DOI Listing
May 2021

In vitro inhibition of human UDP-glucuronosyltransferase (UGT) 1A1 by osimertinib, and prediction of in vivo drug-drug interactions.

Toxicol Lett 2021 Sep 24;348:10-17. Epub 2021 May 24.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, 124221, China. Electronic address:

Osimertinib is the only third-generation epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI) approved by Food and Drug Administration (FDA). This study aimed to know the inhibitory effect of osimertinib on human UDP-glucosyltransferases (UGTs) and human liver microsomes (HLMs), as well as to identify its potential to cause drug-drug interaction (DDI) arising from the modulation of UGT activity. High inhibitory effect of osimertinib was shown towards UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A10, 2B7 and 2B15. Especially, osimertinib exhibited competitive inhibition against UGT1A1 with a K of 0.87 ± 0.12 μM. It also noncompetitively inhibited SN-38 glucuronidation in pooled HLMs with a K of 3.32 ± 0.25 μM. Results from quantitative prediction study indicated that osimertinib administered at 80 mg/day may result in a 4.83 % increase in the AUC of drugs mainly metabolized by UGT1A1, implying low risk of DDI via liver metabolism. However, the ratios of [I]/K are much higher than 11 in HLMs and recombinant UGT1A1, indicating a risk for interaction in intestine. The effects of osimertinib on intestinal UGT should be paid more attention on to avoid unnecessary clinical DDI risks.
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http://dx.doi.org/10.1016/j.toxlet.2021.05.004DOI Listing
September 2021

Comparison of the drug-drug interactions potential of ibrutinib and acalabrutinib via inhibition of UDP-glucuronosyltransferase.

Toxicol Appl Pharmacol 2021 08 24;424:115595. Epub 2021 May 24.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin 124221, China. Electronic address:

Ibrutinib and acalabrutinib are two Bruton's tyrosine kinase (BTK) inhibitors which have gained Food and Drug Administration (FDA) approval for the treatment of various B cell malignancies. Herein, we investigated the effects of the two drugs on UDP-glucuronosyltransferase (UGT) activities to evaluate their potential risk for drug-drug interactions (DDIs) via UGT inhibition. Our data indicated that ibrutinib exerted broad inhibition on most of UGTs, including a potent competitive inhibition against UGT1A1 with a K value of 0.90 ± 0.03 μM, a noncompetitive inhibition against UGT1A3 and UGT1A7 with K values of 0.88 ± 0.03 μM and 2.52 ± 0.23 μM, respectively, while acalabrutinib only exhibited weak UGT inhibition towards all tested UGT isoforms. DDI risk prediction suggested that the inhibition against UGT1A1 and UGT1A3 by ibrutinib might bring a potential DDIs risk, while acalabrutinib was unlikely to trigger clinically significant UGT-mediated DDIs due to its weak effects. Our study raises an alarm bell about potential DDI risk associated with ibrutinib, however, the extrapolation from in vitro data to in vivo drug interactions should be taken with caution, and additional systemic study is needed.
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http://dx.doi.org/10.1016/j.taap.2021.115595DOI Listing
August 2021

Effect of PDCA-based nursing management model on the quality of life and complications of patients with acute leukemia undergoing chemotherapy.

Am J Transl Res 2021 15;13(4):3246-3253. Epub 2021 Apr 15.

Department of Emergency, Affiliated Hospital of Jiangnan University Wuxi, Jiangsu Province, China.

Objective: To assess the influence of PDCA-based nursing management model on the quality of life (QOL) and complications of patients with acute leukemia undergoing chemotherapy.

Methods: In this study, we randomly divided 118 patients with acute leukemia undergoing chemotherapy in our hospital into an observation group (n=59) and a control group (n=59). The control group was implemented routine nursing while the observation group was implemented PDCA-based nursing management. The anxiety, depression, QOL, cancer fatigue, total complication rate, sleep quality, and patients' satisfaction were compared between the two groups.

Results: The SAS and SDS scores of the observation group were significantly lower than those of the control group (P<0.05). The scores of physical function, general health, social function, emotional role, and mental health of the observation group were superior to those of the control group (all P<0.05). The 4 dimensions of behavior/severity, sense, emotion and cognition/mood in the observation group were significantly lower than those of the control group (all P<0.05). The incidence of complications such as nausea and vomiting, infection, bleeding, phlebitis, bone marrow suppression and mucositis in the observation group was significantly lower than that in the control group (P<0.05). The scores of sleep quality in the observation group were significantly lower than those of the control group (all P<0.05). The observation group's satisfaction with PDCA-based nursing management was markedly higher than that of the control group (P<0.05).

Conclusion: The PDCA-based nursing management model applied to patients with acute leukemia undergoing chemotherapy has shown good effects, which can improve depression, anxiety, cancer fatigue, sleep quality and QOL. It also significantly reduced the incidence of complications and improved patients' satisfaction, which was worth of clinical application.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129232PMC
April 2021

The Role of Fibroblast Growth Factor 19 in Hepatocellular Carcinoma.

Am J Pathol 2021 07 14;191(7):1180-1192. Epub 2021 May 14.

Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address:

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the third leading cause of cancer-related deaths worldwide. Liver resection or liver transplantation is the most effective therapy for HCC because drugs approved by the US Food and Drug Administration to treat patients with unresectable HCC have an unfavorable overall survival rate. Therefore, the development of biomarkers for early diagnosis and effective therapy strategies are still necessary to improve patient outcomes. Fibroblast growth factor (FGF) 19 was amplified in patients with HCC from various studies, including patients from The Cancer Genome Atlas. FGF19 plays a syngeneic function with other signaling pathways in primary liver cancer development, such as epidermal growth factor receptor, Wnt/β-catenin, the endoplasmic reticulum-related signaling pathway, STAT3/IL-6, RAS, and extracellular signal-regulated protein kinase, among others. The current review presents a comprehensive description of the FGF19 signaling pathway involved in liver cancer development. The use of big data and bioinformatic analysis can provide useful clues for further studies of the FGF19 pathway in HCC, including its application as a biomarker, targeted therapy, and combination therapy strategies.
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http://dx.doi.org/10.1016/j.ajpath.2021.04.014DOI Listing
July 2021

A huge malignant phyllodes tumor of the breast with osteoclast-like giant cells: a case report.

Gland Surg 2021 Apr;10(4):1508-1514

Department of Breast Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, China.

The malignant phyllodes tumor (PT) of the breasts is a rare type of fibroepithelial neoplasm. Osteoclast-like giant cells (OLGCs) exist in many types of tumors. But malignant PTs with OLGCs were rarely reported. Here, we presented a case of a 49-year-old woman who had a 23 cm ×21 cm ×6 cm mass which was growing for 2 years in her left breast. The patient had moderate anemia due to the hemorrhage and exudation on the surface of the tumor. The imaging examinations such as PET-CT found no lymphatic involvement and distant metastasis. We performed mastectomy with a 2 cm surgical margin and free skin flap transplantation to restore the big wound. The vacuum assisted closure (VAC) system was used to promote wound healing. Histological examination of the surgical specimen showed atypical spindle-like stroma cells, marked nuclear pleomorphism, focal necrosis, and mitotic activity. Typical leaf-like architectures of PTs were observed in some regions. OLGCs were found in many sections of the tumor with a number of vascular proliferations. The final diagnosis was malignant PT with OLGCs. After a three-month follow-up, no local recurrence or metastasis was found. Autogenous skin grafts with VAC are available for large area skin defect after excising a huge breast tumor. The presence of OLGCs in malignant tumors may be related to necrosis and hemorrhage of the tumor. These findings also provide opportunities for understanding the mechanisms of tumor formation and development.
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http://dx.doi.org/10.21037/gs-20-845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102212PMC
April 2021

Risk prediction of drug-drug interaction potential of phenytoin and miconazole topical formulations.

Chem Biol Interact 2021 Jul 4;343:109498. Epub 2021 May 4.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, 124221, China. Electronic address:

The drug-drug interaction (DDI) risk of phenytoin with several topical formulations of miconazole is still unclear. The present investigation conducted in vitro-in vivo extrapolation to predict the potential risks. Our data indicated that miconazole potently inhibited phenytoin hydroxylation in both pooled human liver microsomes (HLMs) and recombinant cytochrome P450 2C9 (CYP2C9) with the K values of 125 ± 7 nM and 30 ± 2 nM, respectively. Quantitative prediction of DDI risk suggests that, beside intravenous administration or swallowed tablet, combination of phenytoin and miconazole high dose oral gel or buccal tablet may also result in a clinically significant increase of phenytoin AUC (>53%) by the inhibition of miconazole against phenytoin hydroxylation, consequently a higher frequency of adverse events, while the coadministration of miconazole vaginal formulation and phenytoin will be safe.
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http://dx.doi.org/10.1016/j.cbi.2021.109498DOI Listing
July 2021

Discovery of novel potential KIT inhibitors for the treatment of gastrointestinal stromal tumor.

Open Life Sci 2021 3;16(1):303-310. Epub 2021 Apr 3.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, 2 Dagong Road, Liaodongwan New District, Panjin 124221, Liaoning, China.

Numerous inhibitors of tyrosine-protein kinase KIT, a receptor tyrosine kinase, have been explored as a viable therapy for the treatment of gastrointestinal stromal tumor (GIST). However, drug resistance due to acquired mutations in KIT makes these drugs almost useless. The present study was designed to screen the novel inhibitors against the activity of the KIT mutants through pharmacophore modeling and molecular docking. The best two pharmacophore models were established using the KIT mutants' crystal complexes and were used to screen the new compounds with possible KIT inhibitory activity against both activation loop and ATP-binding mutants. As a result, two compounds were identified as potential candidates from the virtual screening, which satisfied the potential binding capabilities, molecular modeling characteristics, and predicted absorption, distribution, metabolism, excretion, toxicity (ADMET) properties. Further molecular docking simulations showed that two compounds made strong hydrogen bond interaction with different KIT mutant proteins. Our results indicated that pharmacophore models based on the receptor-ligand complex had excellent ability to screen KIT inhibitors, and two compounds may have the potential to develop further as the future KIT inhibitors for GIST treatment.
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http://dx.doi.org/10.1515/biol-2021-0036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020195PMC
April 2021

High Chromosomal Stability and Immortalized Totipotency Characterize Long-Term Tissue Cultures of Chinese Ginseng ().

Genes (Basel) 2021 03 31;12(4). Epub 2021 Mar 31.

Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China.

Chinese ginseng ( C. A. Meyer) is a highly cherished traditional Chinese medicine, with several confirmed medical effects and many more asserted health-boosting functions. Somatic chromosomal instability (CIN) is a hallmark of many types of human cancers and also related to other pathogenic conditions such as miscarriages and intellectual disabilities, hence, the study of this phenomenon is of wide scientific and translational medical significance. CIN also ubiquitously occurs in cultured plant cells, and is implicated as a major cause of the rapid decline/loss of totipotency with culture duration, which represents a major hindrance to the application of transgenic technologies in crop improvement. Here, we report two salient features of long-term cultured callus cells of ginseng, i.e., high chromosomal stability and virtually immortalized totipotency. Specifically, we document that our callus of ginseng, which has been subcultured for 12 consecutive years, remained highly stable at the chromosomal level and showed little decline in totipotency. We show that these remarkable features of cultured ginseng cells are likely relevant to the robust homeostasis of the transcriptional expression of specific genes (i.e., genes related to tissue totipotency and chromosomal stability) implicated in the manifestation of these two complex phenotypes. To our knowledge, these two properties of ginseng have not been observed in any animals (with respect to somatic chromosomal stability) and other plants. We posit that further exploration of the molecular mechanisms underlying these unique properties of ginseng, especially somatic chromosomal stability in protracted culture duration, may provide novel clues to the mechanistic understanding of the occurrence of CIN in human disease.
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http://dx.doi.org/10.3390/genes12040514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067114PMC
March 2021

The deubiquitinating enzyme USP15 stabilizes ERα and promotes breast cancer progression.

Cell Death Dis 2021 03 26;12(4):329. Epub 2021 Mar 26.

Affiliated Cancer Hospital & institute of Guangzhou Medical University, Guangzhou, 510095, China.

Breast cancer has the highest incidence and mortality in women worldwide. There are 70% of breast cancers considered as estrogen receptor α (ERα) positive. Therefore, the ERα-targeted therapy has become one of the most effective solution for patients with breast cancer. Whereas a better understanding of ERα regulation is critical to shape evolutional treatments for breast cancer. By exploring the regulatory mechanisms of ERα at levels of post-translational modifications, we identified the deubiquitinase USP15 as a novel protector for preventing ERα degradation and a critical driver for breast cancer progression. Specifically, we demonstrated that USP15 promoted the proliferation of ERα, but not ERα breast cancer, in vivo and in vitro. Meanwhile, USP15 knockdown notably enhanced the antitumor activities of tamoxifen on breast cancer cells. Importantly, USP15 knockdown induced the downregulation of ERα protein via promoting its K48-linked ubiquitination, which is required for proliferative inhibition of breast cancer cells. These findings not only provide a novel treatment for overcoming resistance to endocrine therapy, but also represent a therapeutic strategy on ERα degradation by targeting USP15-ERα axis.
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http://dx.doi.org/10.1038/s41419-021-03607-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997968PMC
March 2021

Large-Scale Morphological Network Efficiency of Human Brain: Cognitive Intelligence and Emotional Intelligence.

Front Aging Neurosci 2021 24;13:605158. Epub 2021 Feb 24.

CAS Key Laboratory of Behavioral Science, Institute of Psychology, Beijing, China.

Network efficiency characterizes how information flows within a network, and it has been used to study the neural basis of cognitive intelligence in adolescence, young adults, and elderly adults, in terms of the white matter in the human brain and functional connectivity networks. However, there were few studies investigating whether the human brain at different ages exhibited different underpins of cognitive and emotional intelligence (EI) from young adults to the middle-aged group, especially in terms of the morphological similarity networks in the human brain. In this study, we used 65 datasets (aging 18-64), including sMRI and behavioral measurements, to study the associations of network efficiency with cognitive intelligence and EI in young adults and the middle-aged group. We proposed a new method of defining the human brain morphological networks using the morphological distribution similarity (including cortical volume, surface area, and thickness). Our results showed inverted age × network efficiency interactions in the relationship of surface-area network efficiency with cognitive intelligence and EI: a negative age × global efficiency (nodal efficiency) interaction in cognitive intelligence, while a positive age × global efficiency (nodal efficiency) interaction in EI. In summary, this study not only proposed a new method of morphological similarity network but also emphasized the developmental effects on the brain mechanisms of intelligence from young adult to middle-aged groups and may promote mental health study on the middle-aged group in the future.
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http://dx.doi.org/10.3389/fnagi.2021.605158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959829PMC
February 2021

Comprehensive genetic profiling of six pulmonary nuclear protein in testis carcinomas with a novel micropapillary histological subtype in two cases.

Hum Pathol 2021 Mar 10;115:56-66. Epub 2021 Mar 10.

Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China. Electronic address:

Nuclear protein in testis (NUT) carcinoma (NC) is a rare and aggressive neoplasm associated with a rearrangement of the NUT gene on chromosome 15q14. To date, genomic alterations of NCs, especially those in the lung, are poorly understood. In this study, immunohistochemistry staining, fluorescence in situ hybridization, and two next-generation sequencing (NGS) panels of 56 and 701 genes were used to explore the clinical, pathological, and genetic profiling of pulmonary NCs. Six pulmonary NC cases were confirmed, with a mean age of 41 years (range: 22-69 years) and a median survival time of 6.5 months (range: 2-19 months). Morphologically, typical abrupt keratinization was observed in four of six cases (67%), and two patients presented a mixed pattern of classical squamous component and micropapillary adenocarcinoma morphology. We also identified a case with NUT gene amplification instead of rearrangement. Furthermore, NGS analysis demonstrated the following fusions: BRD4-NUTM1 (2/4 cases) and NSD3-NUTM1 (2/4 cases), and the analysis highlighted 53 gene mutations, including 50 (94.3%, 50/53) single-nucleotide variations (SNVs) and three (5.7%, 3/53) long insertions/deletions. SNVs of MUC16 were the most common and occurred in three cases (75%). Moreover, SNVs of EPHA8, FANCA, TRIO, and USP6 were detected in two of four cases (50%). These 53 mutated genes were involved in 13 functional pathways based on enrichment analysis, especially in the PI3K-Akt signaling pathway. Finally, none of the cases showed obvious copy number variations and had low tumor mutational burden and stable microsatellite sites.
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http://dx.doi.org/10.1016/j.humpath.2021.02.004DOI Listing
March 2021

Adult pulmonary Langerhans cell histiocytosis might consist of two distinct groups: isolated form and extrapulmonary recidivism type.

Ann Transl Med 2021 Feb;9(4):357

Department of Pathology, West China Hospital of Sichuan University, Chengdu, China.

Background: Adult pulmonary Langerhans cell histiocytosis (PLCH) is a rare form of Langerhans cell histiocytosis (LCH) that typically occurs in cigarette smokers. The clinical course of PLCH is unpredictable; the disease may resolve spontaneously, or lead to multi-organ failure and death. To better understand this idiopathic disease, we retrospectively overviewed a cohort of Asian patients with PLCHs.

Methods: Herein, we have provided detailed clinicopathological features and molecular findings of PLCHs in a Southwestern Chinese population, including the expressions of apoptotic protein P16, programmed cell death 1 (PD-1), and programmed cell death-ligand 1 (PD-L1). Importantly, the mutation was observed in this cohort.

Results: In accordance with the follow up data, the cohort was subdivided into two groups, an isolated pulmonary group and extrapulmonary recidivism group. Among the isolated group, the participants were predominantly young males (<40 years old), with a history of smoking, respiratory symptoms (cough and difficulty breathing), showed more cystic lesions in computed tomography (CT) scanning, had more cellular Langerhans granulomas under the microscope, overexpression of P16 (66.7%), high PD-1 (100%) and low PD-L1 (33.3%) expressions, and no mutation was detected. In contrast, the extrapulmonary recidivism group showed significantly older age (>40 years old), recurrent spontaneous pneumothorax, more nodular changes in CT scanning, more interstitial fibrosis histologically, expression rates of 100% of P16, 66.7% of PD-1, and 33.3% of PD-L1; and importantly, mutation was detected in 33.3% of this subdivision.

Conclusions: We found that adult PLCH might consist of two distinct groups: an isolated form and extrapulmonary recidivism PLCH. Overexpression of P16 could be a diagnostic biomarker for PLCH. An extremely low mutation rate of the gene in adult PLCH in our cohort indicated that there might be other pathogeneses for this disease among Asian patients.
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http://dx.doi.org/10.21037/atm-20-8141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944282PMC
February 2021

Long Noncoding RNA UCA1 Is Related to Autophagy and Apoptosis in Endometrial Stromal Cells.

Front Oncol 2020 18;10:618472. Epub 2021 Feb 18.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

Research Question: The expression of the long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) in embryonic tissues is higher than that in most cancer tissues, such as bladder cancer, indicating that RNA is a carcinoembryonic antigen. However, there are no published reports on the role of UCA1 in endometriosis (EMS). Therefore, to address this gap in knowledge, we assessed the potential role of lncRNA UCA1 in the pathogenesis and progression of EMS.

Design: To verify the expression of UCA1 in EMS, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used. RNA interference (siRNA) was used to study the biological function of UCA1 in EMS .

Results: qRT-PCR analysis showed that the expression of lncRNA UCA1 in EMS was increased (P<0.01). Knockdown of UCA1 significantly inhibited the proliferation of endometrial stromal cells (ESCs) and induced autophagy and apoptosis.

Conclusion: UCA1 is highly expressed in EMS and promotes the proliferation of ESCs but suppresses autophagy and apoptosis. In EMS, UCA1 may be a prognostic marker and therapeutic target.
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http://dx.doi.org/10.3389/fonc.2020.618472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931686PMC
February 2021

Molecular epidemiological characteristics of echovirus 6 in mainland China: extensive circulation of genotype F from 2007 to 2018.

Arch Virol 2021 May 26;166(5):1305-1312. Epub 2021 Feb 26.

Medical School, Anhui University of Science and Technology, Huainan, 232001, Anhui, People's Republic of China.

Echovirus 6 (E6) is associated with various clinical diseases and is frequently detected in environmental sewage. Despite its high prevalence in humans and the environment, little is known about its molecular phylogeography in mainland China. In this study, 114 of 21,539 (0.53%) clinical specimens from hand, foot, and mouth disease (HFMD) cases collected between 2007 and 2018 were positive for E6. The complete VP1 sequences of 87 representative E6 strains, including 24 strains from this study, were used to investigate the evolutionary genetic characteristics and geographical spread of E6 strains. Phylogenetic analysis based on VP1 nucleotide sequence divergence showed that, globally, E6 strains can be grouped into six genotypes, designated A to F. Chinese E6 strains collected between 1988 and 2018 were found to belong to genotypes C, E, and F, with genotype F being predominant from 2007 to 2018. There was no significant difference in the geographical distribution of each genotype. The evolutionary rate of E6 was estimated to be 3.631 × 10 substitutions site year (95% highest posterior density [HPD]: 3.2406 × 10-4.031 × 10 substitutions site year) by Bayesian MCMC analysis. The most recent common ancestor of the E6 genotypes was traced back to 1863, whereas their common ancestor in China was traced back to around 1962. A small genetic shift was detected in the Chinese E6 population size in 2009 according to Bayesian skyline analysis, which indicated that there might have been an epidemic around that year.
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http://dx.doi.org/10.1007/s00705-020-04934-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036204PMC
May 2021
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