Publications by authors named "Jie He"

1,173 Publications

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Early warning of citric acid overdose and timely adjustment of regional citrate anticoagulation based on machine learning methods.

BMC Med Inform Decis Mak 2021 Jul 30;21(Suppl 2):126. Epub 2021 Jul 30.

Department of Primary Care and Family Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China.

Background: Regional citrate anticoagulation (RCA) is an important local anticoagulation method during bedside continuous renal replacement therapy. To improve patient safety and achieve computer assisted dose monitoring and control, we took intensive care units patients into cohort and aiming at developing a data-driven machine learning model to give early warning of citric acid overdose and provide adjustment suggestions on citrate pumping rate and 10% calcium gluconate input rate for RCA treatment.

Methods: Patient age, gender, pumped citric acid dose value, 5% NaHCO solvent, replacement fluid solvent, body temperature value, and replacement fluid PH value as clinical features, models attempted to classify patients who received regional citrate anticoagulation into correct outcome category. Four models, Adaboost, XGBoost, support vector machine (SVM) and shallow neural network, were compared on the performance of predicting outcomes. Prediction results were evaluated using accuracy, precision, recall and F1-score.

Results: For classifying patients at the early stages of citric acid treatment, the accuracy of neutral networks model is higher than Adaboost, XGBoost and SVM, the F1-score of shallow neutral networks (90.77%) is overall outperformed than other models (88.40%, 82.17% and 88.96% for Adaboost, XGBoost and SVM). Extended experiment and validation were further conducted using the MIMIC-III database, the F1-scores for shallow neutral networks, Adaboost, XGBoost and SVM are 80.00%, 80.46%, 80.37% and 78.90%, the AUCs are 0.8638, 0.8086, 0.8466 and 0.7919 respectively.

Conclusion: The results of this study demonstrated the feasibility and performance of machine learning methods for monitoring and adjusting local regional citrate anticoagulation, and further provide decision-making recommendations to clinicians point-of-care.
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http://dx.doi.org/10.1186/s12911-021-01489-8DOI Listing
July 2021

S100A7 as a potential diagnostic and prognostic biomarker of esophageal squamous cell carcinoma promotes M2 macrophage infiltration and angiogenesis.

Clin Transl Med 2021 Jul;11(7):e459

Department of Thoracic Surgery, State Key Laboratory of Molecular Oncology/National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Dysregulated expression of S100A7 is found in several cancers and plays an important role in tumor progression; however, its carcinogenic role in esophageal squamous carcinoma (ESCC) is still poorly understood. Here, we identified that the levels of S100A7 were remarkably upregulated in 341 tumor tissues (P < .001) and 274 serum samples (P < .001) of ESCC patients compared with normal control. It was an independent prognostic factor (P = .026). Furthermore, a new diagnostic model for ESCC based on serum S100A7, SCC, and crfra21-1 was established with area under curve (AUC) up to 0.863 (95% CI: 0.802-0.925). Mechanically, we found upregulated S100A7 could promote cell migration and proliferation through intracellular binding to JAB1 and paracrine interaction with RAGE receptors and then activates the downstream signaling pathways. In addition, exocrine S100A7 could promote M2 macrophage infiltration and polarization by up-regulating M2 macrophage associated proteins, and tumor angiogenesis by enhancing the activation of p-ErK and p-FAK pathways. Further animal experiments confirmed the role of S100A7 in promoting M2 macrophage infiltration and angiogenesis in ESCC. In conclusion, these findings highlighted the potential diagnostic and prognostic value of S100A7 in patients with ESCC. Meanwhile, our results reveal that S100A7 promotes tumor progression by activating oncogenic pathways and remodeling tumor microenvironment, which paving the way for the progress of S100A7 as a therapeutic target for cancer treatment.
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http://dx.doi.org/10.1002/ctm2.459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265170PMC
July 2021

Wah Soon Chow, a teacher, a friend and a colleague.

Photosynth Res 2021 Jul 28. Epub 2021 Jul 28.

Climate Change Cluster (C3), University of Technology Sydney, Sydney, NSW, 2007, Australia.

To finish this special issue, some friends, colleagues and students of Prof. Chow (Emeritus Professor, the Research School of Biology, the Australian National University) have written small tributes to acknowledge not only his eminent career but to describe his wonderful personality.
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http://dx.doi.org/10.1007/s11120-021-00864-wDOI Listing
July 2021

Risk factors for gastric cancer: a large-scale, population-based case-control study.

Chin Med J (Engl) 2021 Jul 22. Epub 2021 Jul 22.

Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College/Chinese Academy of Medical Sciences Key Laboratory for National Cancer Big Data Analysis and Implement, Beijing 100021, China Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Background: Early detection of gastric cancer (GC) has been the topic of major efforts in China. This study aimed to explore the risk factors associated with GC and to provide evidence for the selection of a high-risk population of GC.

Methods: Based on the cancer screening cohort of the National Cancer Screening Program in Urban China, GC patients diagnosed by endoscopy and pathological examinations constituted the case group, and controls were 1:3 matched by sex and age (±5 years) individually. The variables were selected by univariable analysis of factors such as body mass index (BMI), dietary habits, lifestyle, stomach disease history, and family history of GC; and multivariable logistic regression was used to analyze the influencing factors of GC and to calculate the odds ratio (OR) of related factors and its 95% confidence interval (CI).

Results: A total of 215 GC cases and 645 matched healthy controls were included in the final analysis, with a median age of 61 years for the case and control groups. Overall analysis showed that high educational level (above primary school) (OR = 0.362, 95% CI = 0.219-0.599, P < 0.001), overweight/obesity (BMI ≥24 kg/m2; OR = 0.489, 95% CI = 0.329-0.726, P < 0.001), cigarette smoking (OR = 3.069, 95% CI = 1.700-5.540, P < 0.001), alcohol consumption (OR = 1.661, 95% CI = 1.028-2.683, P = 0.038), history of stomach disease (OR = 6.917, 95% CI = 4.594-10.416, P < 0.001), and family history of GC in first-degree relatives (OR = 4.291, 95% CI = 1.661-11.084, P = 0.003) were significantly correlated with the occurrence of GC. Subgroup analyses by age and gender indicated that GC risk was still increased in the presence of a history of stomach disease. A history of chronic gastritis, gastric ulcer, or gastric polyposis was positively associated with GC, with adjusted ORs of 4.155 (95% CI = 2.711-6.368), 1.839 (95% CI = 1.028-3.288), and 2.752 (95% CI = 1.197-6.326).

Conclusions: Subjects who smoke, drink, with history of stomach disease and family history of GC in first-degree relatives are the high-risk populations for GC. Therefore, attention should be paid to these subjects for GC screening.
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http://dx.doi.org/10.1097/CM9.0000000000001652DOI Listing
July 2021

Ubiquitination Destabilizes Protein Sphingosine Kinase 2 to Regulate Glioma Malignancy.

Front Cell Neurosci 2021 7;15:660354. Epub 2021 Jul 7.

Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.

Gliomas are the most common and lethal malignant tumor in the central nervous system. The tumor oncogene sphingosine kinase 2 (SphK2) was previously found to be upregulated in glioma tissues and enhance glioma cell epithelial-to-mesenchymal transition through the AKT/β-catenin pathway. Nevertheless, ubiquitination of SphK2 protein has yet to be well elucidated. In this study, mass spectrometry analysis was performed to identify proteins that interacted with SphK2 protein. Co-immunoprecipitation (co-IP) and immunoblotting (IB) were used to prove the specific interaction between SphK2 protein and the neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L) protein. Fluorescence microscopy was used for detecting the distribution of related proteins. Ubiquitylation assay was utilized to characterize that SphK2 was ubiquitylated by NEDD4L. Cell viability assay, flow cytometry assay, and transwell invasion assay were performed to illustrate the roles of NEDD4L-mediated SphK2 ubiquitination in glioma viability, apoptosis, and invasion, respectively. We found that NEDD4L directly interacted with SphK2 and ubiquinated it for degradation. Ubiquitination of SphK2 mediated by NEDD4L overexpression suppressed glioma cell viability and invasion but promoted glioma apoptosis. Knockdown of NEDD4L presented opposite results. Moreover, further results suggested that ubiquitination of SphK2 regulated glioma malignancy the AKT/β-catenin pathway. assay also supported the above findings. This study reveals that NEDD4L mediates SphK2 ubiquitination to regulate glioma malignancy and may provide some meaningful suggestions for glioma treatment.
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http://dx.doi.org/10.3389/fncel.2021.660354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292629PMC
July 2021

Catastrophic Health Expenditure and Its Determinants Among Households With Breast Cancer Patients in China: A Multicentre, Cross-Sectional Survey.

Front Public Health 2021 5;9:704700. Epub 2021 Jul 5.

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Although numerous studies have examined catastrophic health expenditures (CHE) worldwide, most focus on the general population, not on specific vulnerable groups. We aimed to analyse the extent and the influencing factors of CHE in households with breast cancer patients in China, and explore the ability of different insurances to protect these households from CHE. A multicentre, cross-sectional interview surveys was conducted in households with breast cancer patients across seven provinces/municipalities in China. CHE were defined as out-of-pocket expenditures ≥ 40% of households' non-food expenditures. Chi-square tests and logistic regression analysis were performed to identify the determinants of CHE in household with breast cancer patients. In the 639 participating households with breast cancer patients, the mean out-of-pocket (OOP) expenditure accounted for ~55.20% of the mean households' non-food expenditures. The overall incidence of CHE was 87.95 and 66.28% before and after insurance compensation, respectively. The logistic regression model revealed that education, disease course, health insurance, treatment method, and income were significant predictors of CHE. The results indicated that medical insurance protects some households with breast cancer patients from the impact of CHE. However, their reimbursement rates were relatively low. Therefore, breast cancer still had a significant catastrophic effect on the economy of households. Policy efforts should focus on improving insurance compensation rates and relieving the economic burden of critical illnesses such as breast cancer.
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http://dx.doi.org/10.3389/fpubh.2021.704700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287064PMC
July 2021

Neutrophil-Lymphocyte Ratio as a Predictive Factor of Growing Malignant Pulmonary Ground-glass Opacity.

Cancer Manag Res 2021 13;13:5651-5655. Epub 2021 Jul 13.

Study Office of Thoracic Surgery, Hebei Medical University, Shijiazhuang, 050017, People's Republic of China.

Background: The object of the study was to elucidate the relationship between the neutrophil-lymphocyte ratio (NLR) and the growth of pulmonary ground-glass opacity (GGO) in stage IA lung adenocarcinoma.

Methods: All patients with GGO following surgical procedures were enrolled, with the time of follow-up and the variation tendency of GGO recorded. Meanwhile, laboratory parameters, age, gender, smoking history, histology, tumor size, and stage were recorded. Logistic regression was used to evaluate the value of NLR and the cutoff value was calculated by SPSS 22.0.

Results: In the whole cohort, 30 cases of growing GGO and 43 cases of stable GGO undergoing surgical procedures were diagnosed as lung adenocarcinoma. There was significant statistical difference between the two groups. Multivariable analysis showed that NLR could predict the GGOs with growth (odds ratio 5.198, 95% confidence interval (95%CI: 1.583-14.581, =0.002). Receiver operating characteristics analysis for NLR showed the optimal cutoff value of 2.38, with a sensitivity of 60.0% and specificity of 81.4%.

Conclusion: Our study demonstrated that the NLR appeared to have value as a promising clinical predictor of GGOs with growth. Further studies are needed to confirm this conclusion.
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http://dx.doi.org/10.2147/CMAR.S319190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286107PMC
July 2021

Author Correction: METTL3 promotes tumour development by decreasing APC expression mediated by APC mRNA N-methyladenosine-dependent YTHDF binding.

Nat Commun 2021 Jul 20;12(1):4529. Epub 2021 Jul 20.

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.

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http://dx.doi.org/10.1038/s41467-021-24860-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292537PMC
July 2021

Myocardial area at risk and salvage in reperfused acute MI measured by texture analysis of cardiac T2 mapping and its prediction value of functional recovery in the convalescent stage.

Int J Cardiovasc Imaging 2021 Jul 19. Epub 2021 Jul 19.

Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.

Objectives: We sought to distinguish area at risk from salvage myocardial zone and to predict left ventricle functional recovery in the convalescent stage by Texture Analysis (TA) of T2-Mapping.

Methods: One hundred and six patients diagnosed with AMI and treated with percutaneous coronary intervention (PCI) underwent acute cardiac magnetic resonance imaging (CMR) and 45 of whom had a subsequent CMR scan following recovery. Cine imaging, T2-Mapping, T2-weighted STIR imaging, and LGE imaging were performed. In the texture analysis, regions of interest (infarcted, salvageable, and remote) were drawn by two blinded, independent readers.

Results: Seven independent texture features on T2-Mapping were selected: Perc.50%, S(2,2)InvDfMom, S(2.-2)AngScMom, S(4,0)Entropy, 45dgrLngREmph, 45dgr_Fraction and 135dr_GLevNonU. Among them, the average value of 135dr_GLevNonU in the infarct zone, AAR zone, and the remote zone was: 61.96±26.03, 31.811±18.933 and 99.839±26.231, respectively. Additionally, 135dr_GLevNonU provided the highest area under the curve (AUC) from the receiver operating characteristic curve (ROC curve) for distinguishing AAR from the infarct zone in each subgroup (all patients, patients with MVO and)were 0.845 ± 0.052 0.855 ± 0.083 and 0.845 ± 0.066, respectively, and were more promise than T2-Mapping mean (p<0.001). The AUC for differentiating AAR from the remote zone is 0.942±0.041. Texture features are not associated with convalescent decreased strain, ejection fraction (EF) or left ventricle remodeling (LVR) in analysis (p>0.05).

Conclusion: TA of T2-mapping can distinguish AAR from both the infarct zone and the remote myocardial zone without LGE imaging in reperfused AMI. However, these features are not able to predict patients' functional recovery in the convalescent stage.
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http://dx.doi.org/10.1007/s10554-021-02336-7DOI Listing
July 2021

The Mechanical Properties of Early Aged Shotcrete under Internal Sulfate Attack.

Materials (Basel) 2021 Jul 2;14(13). Epub 2021 Jul 2.

South City Power Supply Branch of State Grid Chongqing Electric Power Company, Chongqing 404100, China.

Shotcrete is the primary material for tunnel support due to its early rapid hardening characteristics. During tunnel construction in a sulfate environment, the hardening law of concrete will be affected. In this study, samples were prepared at six different curing times and immersed in four different concentrations of sulfate solutions. A uniaxial test was conducted and analyzed to investigate the effect of sulfate attack on the mechanical properties of early aged shotcrete materials. Results indicated that waterlogged shotcrete does not have apparent cracks on the outside. The stress-strain curve or ultimate compressive strength of the samples showed that the effect of sulfate on shotcrete should be differentiated into chemical and physical sulfate attacks, according to the concentration of sulfate ions. The two parameters in the equation of the hardening behaviors of sulfate attack samples, ultimate compressive strength, and time constant, are related to sulfate concentration. The crack damage stress threshold of samples demonstrates that high-concentration sulfate corrosion leads to an impact on the durability of shotcrete.
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http://dx.doi.org/10.3390/ma14133726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269896PMC
July 2021

Prognostic nutritional index, a novel biomarker which predicts worse prognosis in diffuse large B cell lymphoma.

Leuk Res 2021 Jul 7;110:106664. Epub 2021 Jul 7.

Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China; Key Laboratory of Hematology of Nanjing Medical University, Nanjing 210029, China; Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing 210029, China. Electronic address:

The prognostic nutritional index (PNI), an indicator of nutritional status and systemic inflammation, is associated with survival in several types of lymphoma. The purpose of this study was to investigate the prognostic value of PNI in diffuse large B cell lymphoma (DLBCL). With three hundred and ten patients were enrolled, the median level of PNI was 45.90 (range 25.30-139.70). According to the receiver operating characteristic (ROC) curve, 44.85 was determined to be the best cutoff value to divide patients into two different groups. With a median follow-up of 33.3 months (range 3.5-118.5), compared with the high PNI group, the 3-year and adjusted 3-year progression-free survival (PFS) and overall survival (OS) were worse in the low PNI group (all P < 0.050). Multivariate Cox analysis suggested that low PNI was an independent risk factor for PFS (hazard ratio (HR) 2.196, 95 % CI 1.197-4.030, P = 0.011) and showed a tendency to predict inferior OS (HR 1.918, 95 % CI 0.932-3.948, P = 0.077). Furthermore, PNI combined with other significant prognostic factors to build a novel prognostic index, namely NPI, was more accurate than the National Comprehensive Cancer Network international prognostic index (NCCN-IPI) to predict worse PFS and had a similar effect on predicting OS. All these findings suggested that PNI, as a novel available biomarker, was of prognostic significance in DLBCL patients.
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http://dx.doi.org/10.1016/j.leukres.2021.106664DOI Listing
July 2021

Identification of the correlations between interleukin-27 (IL-27) and immune-inflammatory imbalance in preterm birth.

Bioengineered 2021 Dec;12(1):3201-3218

Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Preterm birth (PTB) is an immune-inflammatory disease that needs to be resolved. This study aimed to identify the role of interleukin-27 (IL-27), an immunomodulatory factor, in PTB and its associated mechanisms. Here, we analyzed the high-throughput of samples data from the maternal-fetal interface to the peripheral circulation obtained from public databases and reported that the elevated IL-27 was involved with the onset of PTB. Further bioinformatics analyses (e.g. GeneMANIA and GSEA) revealed that IL-27 overexpression in the peripheral circulation as well as maternal-fetal interface is related to the activation of the immune-inflammatory process represented by IFN-γ signaling, etc. In addition, IL-27 and immune infiltration correlation analysis demonstrated that IL-27 mediates this immune-inflammatory imbalance, plausibly mainly through monocyte-macrophage and neutrophils. This finding was further validated by analyzing additional datasets. Overall, this is the first study to elaborate on the role of IL-27-mediated immuno-inflammation in PTB from the perspective of bioinformatics, which may provide a novel strategy for the prevention and treatment of PTB.
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http://dx.doi.org/10.1080/21655979.2021.1945894DOI Listing
December 2021

Therapeutic Effect and Cost-Benefit Analysis of Three Different Nutritional Schemes for Esophageal Cancer Patients in the Early Post-operative Period.

Front Nutr 2021 17;8:651596. Epub 2021 Jun 17.

Department of Nutrition, Xinqiao Hospital of Army Medical University, Chongqing, China.

To retrospectively investigate the comparative efficacy, safety and cost-benefits of three nutritional treatment schemes including short peptide jejunal nutrition (SPJN), whole protein jejunal nutrition (WPJN), and partial parenteral nutrition (PPN) in patients underwent esophagectomy for esophageal cancer in our hospital. This study was carried out in accordance with the conceptual framework of nutritional therapy in fast-track rehabilitation surgery. We retrospectively reviewed 305 patients who were assigned to receive esophagectomy for esophageal cancer. Eligible patients was naturally divided into SPJN group [ = 98 (32.1%)], WPJN group [ = 95 (31.1%)], and PPN group [ = 112 (36.7%)] according to the type of nutritional scheme which was actually prescribed to patients by the attendingphysician in clinical practice. The differences of the serum total protein (TP), albumin (ALB), pre-albumin (PA), hemoglobin (HGB), white blood cells (WBCs), red blood cells (RBCs) and neutrophils were compared among 3 nutritional schemes groups. We also investigated the relationship of the fluid intake, urine output, gastric juice drainage volume and thoracic drainage volume among 3 nutritional groups at 3 days after surgery. Moreover, the differences of cost-benefit indexes, complications, length of hospitalization and hospital expenditure were also compared. The serum TP, ALB, and PA in the SPJN group were all higher than those in the WPJN and PPN groups ( < 0.05). The gastric juice volume of gastrointestinal decompression drainage and fluid volume of thoracic drainage in the SPJN group were all less than that in the WPJN group ( < 0.05). The overall hospital stay and post-operative hospital stay in the SPJN group were all shorter than that in WPJN group ( < 0.05). Moreover, the incidence of post-operative complications including anastomotic leakage, infection, and gastrointestinal reaction was remarkably lower in the SPJN group compared to the WPJN group ( < 0.05). Interesting, hospital expenditure in the PPN group was less than that in the SPJN and the WPJN groups ( < 0.001). Patients may obtain benefits in improving protein level after receiving SPJN scheme at the early stage after esophagectomy. Meanwhile, patients may obtain benefits in improving post-operative complications and hospital stay after receiving SPJN or PPN compared to WPJN protocol. However, the difference between SPJN and PPN requires further study because no difference was detected in terms of clinical outcomes including complications and the length of hospitalization although PPN may achieve a possible decrease of medical expenditure.
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http://dx.doi.org/10.3389/fnut.2021.651596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247476PMC
June 2021

LAMC1 upregulation via TGFβ induces inflammatory cancer-associated fibroblasts in esophageal squamous cell carcinoma via NF-κB-CXCL1-STAT3.

Mol Oncol 2021 Jul 4. Epub 2021 Jul 4.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Cancer-associated fibroblasts (CAF) are a heterogeneous cell population within the tumor microenvironment,and play an important role in tumor development. By regulating the heterogeneity of CAF, transforming growth factor β (TGFβ) influences tumor development. Here, we explored oncogenes regulated by TGFβ1 that are also involved in signaling pathways and interactions within the tumor microenvironment. We analyzed sequencing data of The Cancer Genome Atlas (TCGA) and our own previously established RNA microarray data (GSE53625), as well as esophageal squamous cell carcinoma (ESCC) cell lines with or without TGFβ1 stimulation. We then focused on laminin subunit gamma 1 (LAMC1), which was overexpressed in ESCC cells, affecting patient prognosis, which could be upregulated by TGFβ1 through the synergistic activation of SMAD family member 4 (SMAD4) and SP1. LAMC1 directly promoted the proliferation and migration of tumor cells, mainly via Akt-NFκB-MMP9/14 signaling. Additionally, LAMC1 promoted CXCL1 secretion, which stimulated the formation of inflammatory CAF (iCAF) through CXCR2-pSTAT3. Inflammatory CAF promoted tumor progression. In summary, we identified the dual mechanism by which the upregulation of LAMC1 by TGFβ in tumor cells not only promotes ESCC proliferation and migration, but also indirectly induces carcinogenesis by stimulating CXCL1 secretion to promote the formation of iCAF. This finding suggests that LAMC1 could be a potential therapeutic target and prognostic marker for ESCC.
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http://dx.doi.org/10.1002/1878-0261.13053DOI Listing
July 2021

Long non-coding RNA HULC stimulates the epithelial-mesenchymal transition process and vasculogenic mimicry in human glioblastoma.

Cancer Med 2021 Jul 2. Epub 2021 Jul 2.

Clinical Pathology Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.

Background: Long non-coding RNA (lncRNA) HULC (highly upregulated in liver cancer) is considered as an oncogenic factor for various malignant tumors. This study aimed to reveal the role of lncRNA HULC in the malignant behavior of glioblastoma (GBM) by exploring its effects on the epithelial-mesenchymal transition (EMT) and vasculogenic mimicry (VM) of human GBM.

Materials And Methods: The contents of VM in 27 GBM samples were assessed by immunohistochemistry-histology and their association with progress-free survival (PFS) was analyzed. Human GBM SHG44 and U87 cells were manipulated to establish stable lncRNA HULC overexpressing and silencing cells by lentivirus-based technology. The effects of altered lncRNA HULC on vasculogenic tubular formation, invasion, and EMT process in GBM cells were tested in vitro and the growth of implanted GBM tumors and their EMT process were examined in vivo.

Results: The numbers of VM were positively associated with disease progression, but negatively with PFS periods of GBM patients. Compared with the control vec cells, lncRNA HULC overexpression significantly increased the tubular formation, invasion, and EMT process of both SHG44 and U87 cells, accompanied by promoting the growth of implanted GBM tumors and EMT process in mice. LncRNA HULC silencing had opposite effects on the tubular formation, invasion, and EMT process as well as tumor growth of GBM cells.

Conclusion: LncRNA HULC stimulates the EMT process and VM in human GBM, and may be a therapeutic target for intervention of GBM.
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http://dx.doi.org/10.1002/cam4.4083DOI Listing
July 2021

[Soil heterogeneity and its interaction with plants in karst areas].

Ying Yong Sheng Tai Xue Bao 2021 Jun;32(6):2249-2258

College of Forestry, Guizhou University, Guiyang 550025, China.

Soil heterogeneity is at a high level in the karst areas, which resulted from the complex habitat. On the one hand, plants have some adaptive strategies to such special habitats by forming certain morphological and physiological characteristics, which result in higher diversity of functional traits. One the other hand, plants improve the physical and chemical properties of soil through a series of life activities. The interactions between plants and soil drive ecosystem structure and function and its responses to global climate change. Here, we summarized the characteristics of soil hete-rogeneity in the karst areas, and reviewed the response of plant functional traits to soil and the feedback of plants to soil. It revealed the coupling mechanism between plants and soil in karst eco-system. We provided a future outlook, including future research contents and directions based on the current research status in this field, which aimed to provide theoretical reference for maintaining the structural and functional stability of fragile karst ecosystems.
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http://dx.doi.org/10.13287/j.1001-9332.202106.006DOI Listing
June 2021

Metamorphic Protein Folding Encodes Multiple Anti- Mechanisms in XCL1.

Pathogens 2021 Jun 17;10(6). Epub 2021 Jun 17.

Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

species cause serious infections requiring prolonged and sometimes toxic therapy. Antimicrobial proteins, such as chemokines, hold great interest as potential additions to the small number of available antifungal drugs. Metamorphic proteins reversibly switch between multiple different folded structures. XCL1 is a metamorphic, antimicrobial chemokine that interconverts between the conserved chemokine fold (an α-β monomer) and an alternate fold (an all-β dimer). Previous work has shown that human XCL1 kills but has not assessed whether one or both XCL1 folds perform this activity. Here, we use structurally locked engineered XCL1 variants and killing assays, adenylate kinase release assays, and propidium iodide uptake assays to demonstrate that both XCL1 folds kill , but they do so via different mechanisms. Our results suggest that the alternate fold kills via membrane disruption, consistent with previous work, and the chemokine fold does not. XCL1 fold-switching thus provides a mechanism to regulate the XCL1 mode of antifungal killing, which could protect surrounding tissue from damage associated with fungal membrane disruption and could allow XCL1 to overcome candidal resistance by switching folds. This work provides inspiration for the future design of switchable, multifunctional antifungal therapeutics.
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http://dx.doi.org/10.3390/pathogens10060762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235156PMC
June 2021

Preparation and Characterization of Mg-Al-B Alloy (MgAlB) Via High-Temperature Sintering.

Materials (Basel) 2021 Jun 28;14(13). Epub 2021 Jun 28.

Institute of Chemical Defense, Academy of Military Sciences, Beijing 102205, China.

Boron and its alloys have long been explored as potential fuel and increasingly replace pure aluminum powder in high-energy formulations. The ignition and burning properties of boron can be improved by making boron alloys. In this study, an Mg-Al-B alloy was synthesized from magnesium, aluminum and boron powders in a 1:1:4 molar ratio by preheating to 600 °C for 30 min, followed by high-temperature sintering in a tube furnace. The effects of sintering temperature (700-1000 °C) and holding time (0.5-10 h) on the phase composition of mixed powders were studied. After the samples were cooled to room temperature, they were ground into powder. The phase composition, micromorphology and the bonding forms of elements of the synthesized samples were studied using XRD, SEM and XPS. The results show that each element exists in the form of simple substance in the alloy. The influence of the sintering temperature on the synthesis reaction of MgAlB is very important, but holding time has little effect on it. With the increase of sintering temperature, the content of the MgAlB phase gradually increases, and the phase content of residual metal gradually decreases. The phase and morphology analyses show that the optimum sintering temperature is 1000 °C with a minimum holding time of 0.5 h. It is expected to be used in gunpowder, propellant, explosives and pyrotechnics with improved characteristics.
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http://dx.doi.org/10.3390/ma14133608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269652PMC
June 2021

Prevalence and risk factors of mcr-1-positive volunteers after colistin banning as animal growth promoter in China: a community-based case-control study.

Clin Microbiol Infect 2021 Jun 28. Epub 2021 Jun 28.

Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China. Electronic address:

Objectives: China banned the use of colistin as animal growth promoter in April 2017. Herein, we report the prevalence of mcr-1 in the intestine of healthy humans and risk factors associated with mcr-1 carriage after the implementation of the ban.

Methods: We recruited 719 healthy volunteers from Shenzhen City from 1 March 2018 to 31 December 2019 to investigate the prevalence of mcr-1 in human intestine, and undertook a case-control study to ascertain the risk factors associated with the mcr-1-positive population. A further comparative study was conducted to identify differences between genetic characteristics of mcr-1-positive and mcr-1-negative Escherichia coli.

Results: Overall, 56 (7.8%, 95% CI 5.9%-10.0%, n = 719) individual faecal samples were positive for mcr-1, and prevalence of mcr-1 among individuals in 2019 (2.4%, 95% CI 8.7%-15.0%, 7/294) was significantly lower than that in 2018 (11.5%, 95% CI 1.0%-4.8%, 49/425) (p < 0.0001). After the colistin ban, animal-derived food (pork and chicken meat) was no longer a risk factor for mcr-1 carriage in human intestine, whereas a higher intake of fish and seafood (>75 g/day) and whole grains (>150 g/day) was associated with higher and lower risk of mcr-1 carriage, respectively (OR 2.175, 95% CI 1.047-4.517; OR 0.045, 95% CI 0.004-0.567). Compared with mcr-1-negative E. coli, the mcr-1-positive E. coli had different patterns of resistance genes and genetic heterogeneity.

Conclusions: Our study implicates aquatic food as beeing associated with mcr-1 carriage in the healthy population, even after the ban on colistin. Dietary modification (e.g. whole grains) may help to combat mcr-1-positive bacterial colonization of the gut.
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http://dx.doi.org/10.1016/j.cmi.2021.06.033DOI Listing
June 2021

Effects of cancer treatment on household impoverishment: a multicentre cross-sectional study in China.

BMJ Open 2021 Jun 30;11(6):e044322. Epub 2021 Jun 30.

Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objectives: To determine the incidence and intensity of household impoverishment induced by cancer treatment in China.

Design: Average income and daily consumption per capita of the households and out-of-pocket payments for cancer care were estimated. Household impoverishment was determined by comparing per capita daily consumption against the Chinese poverty line (CPL, US$1.2) and the World Bank poverty line (WBPL, US$1.9) for 2015. Both pre-treatment and post-treatment consumptions were calculated assuming that the households would divert daily consumption money to pay for cancer treatment.

Participants: Cancer patients diagnosed initially from 1 January 2015 to 31 December 2016 who had received cancer treatment subsequently. Those with multiple cancer diagnoses were excluded.

Data Sources: A household questionnaire survey was conducted on 2534 cancer patients selected from nine hospitals in seven provinces through two-stage cluster/convenience sampling.

Findings: 5.89% (CPL) to 12.94% (WBPL) households were impoverished after paying for cancer treatment. The adjusted OR (AOR) of post-treatment impoverishment was higher for older patients (AOR=2.666-4.187 for ≥50 years vs <50 years, p<0.001), those resided in central region (AOR=2.619 vs eastern, p<0.01) and those with lower income (AOR=0.024-0.187 in higher income households vs the lowest 20%, p<0.001). The patients without coverage from social health insurance had higher OR (AOR=1.880, p=0.040) of experiencing post-treatment household impoverishment than those enrolled with the insurance for urban employees. Cancer treatment is associated with an increase of 5.79% (CPL) and 12.45% (WBPL) in incidence of household impoverishment. The median annual consumption gap per capita underneath the poverty line accumulated by the impoverished households reached US$128 (CPL) or US$212 (WBPL). US$31 170 395 (CPL) or US$115 238 459 (WBPL) were needed to avoid household impoverishment induced by cancer treatment in China.

Conclusions: The financial burden of cancer treatment imposes a significant risk of household impoverishment despite wide coverage of social health insurance in China.
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http://dx.doi.org/10.1136/bmjopen-2020-044322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246348PMC
June 2021

Tumor-infiltrating CD8 T cell is prognostic and predicts adjuvant chemotherapy benefit in patients with limited-stage small cell esophageal carcinoma.

Clin Transl Med 2021 Jun;11(6):e456

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.1002/ctm2.456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236121PMC
June 2021

A Novel Immune-Related Seventeen-Gene Signature for Predicting Early Stage Lung Squamous Cell Carcinoma Prognosis.

Front Immunol 2021 11;12:665407. Epub 2021 Jun 11.

Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.

With the increasingly early stage lung squamous cell carcinoma (LUSC) being discovered, there is an urgent need for a comprehensive analysis of the prognostic characteristics of early stage LUSC. Here, we developed an immune-related gene signature for outcome prediction of early stage LUSC based on three independent cohorts. Differentially expressed genes (DEGs) were identified using CIBERSORT and ESTMATE algorithm. Then, a 17-immune-related gene (RPRM, APOH, SSX1, MSGN1, HPR, ISM2, FGA, LBP, HAS1, CSF2, RETN, CCL2, CCL21, MMP19, PTGIS, F13A1, C1QTNF1) signature was identified using univariate Cox regression, LASSO regression and stepwise multivariable Cox analysis based on the verified DEGs from 401 cases in The Cancer Genome Atlas (TCGA) database. Subsequently, a cohort of GSE74777 containing 107 cases downloaded from Gene Expression Omnibus (GEO) database and an independent data set consisting of 36 frozen tissues collected from National Cancer Center were used to validate the predictive value of the signature. Seventeen immune-related genes were identified from TCGA cohort, which were further used to establish a classification system to construct cases into high- and low-risk groups in terms of overall survival. This classifier was still an independent prognostic factor in multivariate analysis. In addition, another two independent cohorts and different clinical subgroups validated the significant predictive value of the signature. Further mechanism research found early stage LUSC patients with high risk had special immune cell infiltration characteristics and gene mutation profiles. In conclusion, we characterized the tumor microenvironment and established a highly predictive model for evaluating the prognosis of early stage LUSC, which may provide a lead for effective immunotherapeutic options tailored for each subtype.
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http://dx.doi.org/10.3389/fimmu.2021.665407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226174PMC
June 2021

Co-occurring gain-of-function mutations in HER2 and HER3 modulate HER2/HER3 activation, oncogenesis, and HER2 inhibitor sensitivity.

Cancer Cell 2021 Jun 22. Epub 2021 Jun 22.

UTSW Simmons Comprehensive Cancer Center, Dallas, 5323 Harry Hines Boulevard, TX 75390, USA; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA.

Activating mutations in HER2 (ERBB2) drive the growth of a subset of breast and other cancers and tend to co-occur with HER3 (ERBB3) missense mutations. The HER2 tyrosine kinase inhibitor neratinib has shown clinical activity against HER2-mutant tumors. To characterize the role of HER3 mutations in HER2-mutant tumors, we integrate computational structural modeling with biochemical and cell biological analyses. Computational modeling predicts that the frequent HER3 kinase domain mutation enhances the affinity of HER2/HER3 and reduces binding of HER2 to its inhibitor neratinib. Co-expression of mutant HER2/HER3 enhances HER2/HER3 co-immunoprecipitation and ligand-independent activation of HER2/HER3 and PI3K/AKT, resulting in enhanced growth, invasiveness, and resistance to HER2-targeted therapies, which can be reversed by combined treatment with PI3Kα inhibitors. Our results provide a mechanistic rationale for the evolutionary selection of co-occurring HER2/HER3 mutations and the recent clinical observations that HER3 mutations are associated with a poor response to neratinib in HER2-mutant cancers.
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http://dx.doi.org/10.1016/j.ccell.2021.06.001DOI Listing
June 2021

PEG-modified subunit vaccine encoding dominant epitope to enhance immune response against spring viraemia of carp virus.

J Fish Dis 2021 Jun 24. Epub 2021 Jun 24.

College of Animal Science and Technology, Northwest A&F University, Yangling, China.

Spring viraemia of carp (SVC) caused by spring viraemia of carp virus (SVCV) can infect almost all fish of cyprinids, which bring huge economic losses to aquaculture. Glycoprotein (G), as the most important antigenic determinant protein of SVCV, is widely considered as an effective method against SVCV. In our previous study, we found that G3 (131 aa) is the potential dominant antigen epitope that induces strong immune responses similar to G protein (510 aa). Here, in order to further improve the immune effect, we reported a subunit vaccine (PEG-G3) constructed by PEG-modified dominant epitope protein (G3). The results of serum antibody production, enzyme activities and immune-related genes expression showed that PEG-G3 induces significantly stronger immune protective responses against SVCV than G3. PEG modification significantly increased the serum antibody level of the vaccine, which increased significantly after immunization and reached the peak at 21 day post-vaccination. T-AOC and AKP activities in the lowest concentration group (5 μg) of PEG-G3 were significantly higher than those in the highest concentration group (20 μg) of G3. In PEG-G3 group, the expression of almost all genes increased at least 4 times compared with the control group. After 14-day challenge, the RPS (relative percentage survival) of the highest concentration of PEG-G3 group was 53.6%, while that of G3 group is 38.9%. Therefore, this work shows that PEG modification and dominant epitope screening may be effective methods to improve the immune protective effect of vaccines and to resist the infection of aquatic animal viral diseases.
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http://dx.doi.org/10.1111/jfd.13481DOI Listing
June 2021

Effect of Postoperative Radiotherapy for Patients With pIIIA-N2 Non-Small Cell Lung Cancer After Complete Resection and Adjuvant Chemotherapy: The Phase 3 PORT-C Randomized Clinical Trial.

JAMA Oncol 2021 Jun 24. Epub 2021 Jun 24.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Importance: The role of postoperative radiotherapy (PORT) has not been well defined in resected pIIIA-N2 non-small cell lung cancer (NSCLC).

Objective: To evaluate the effect of PORT using modern techniques on survival and safety in patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy.

Design, Setting, And Participants: The PORT-C randomized clinical trial was conducted in 394 patients with pIIIA-N2 NSCLC treated with complete resection and 4 cycles of platinum-based chemotherapy between January 2009 and December 2017. Data were analyzed between March 2019 and December 2020.

Interventions: Patients were randomized equally into the PORT arm (n = 202) or the observation arm (n = 192). The total dose of PORT was 50 Gy.

Main Outcomes And Measures: The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival, and toxic effects.

Results: In total, 394 patients were enrolled and 364 were eligible, with a median (range) age of 55 (25-70) years. There were 202 (55.5%) male and 162 (44.5%) female patients. The median follow-up was 46.0 (95% CI, 41.9-51.4) months, and 230 DFS events were reported. There were 184 patients in the PORT arm and 180 patients in the observation arm. The 3-year DFS rates were 40.5% with PORT vs 32.7% with observation (median, 22.1 vs 18.6 months), and the difference in DFS was not statistically significant without adjustment (hazard ratio [HR], 0.84; 95% CI, 0.65-1.09; P = .20), though it was significant with preplanned yet exploratory analysis (stratified analysis by the number of detected lymph nodes and positive lymph nodes, HR, 0.75; log-rank P = .04). The 3-year OS rates were 78.3% vs 82.8% (HR, 1.02; P = .93), and LRFS was 66.5% vs 59.7% (HR, 0.71; 95% CI, 0.51-0.97; P = .03), respectively. For 310 per-protocol patients (140 with PORT and 170 with observation), PORT significantly improved DFS (42.8% vs 30.6%; HR, 0.75; 95% CI, 0.57-1.00; P = .05) but not OS (HR, 0.83; 95% CI, 0.53-1.30; P = .41). The 3-year local recurrence only rates were 9.5% and 18.3% in the 2 arms, respectively (Fine-Gray HR, 0.55; Gray test P = .04). No radiotherapy-related grade 4 or 5 adverse event was observed.

Conclusions And Relevance: In this phase 3 randomized clinical trial of patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy, PORT did not improve DFS. Further studies exploring patients who might best benefit from PORT are needed.

Trial Registration: ClinicalTrials.gov Identifier: NCT00880971.
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http://dx.doi.org/10.1001/jamaoncol.2021.1910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227450PMC
June 2021

Outcomes of long versus short stent cronus hybrid prosthesis in type A aortic dissection: A single centre experience.

J Card Surg 2021 Jun 23. Epub 2021 Jun 23.

Department of Cardiovascular Surgery, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

Objectives: The frozen elephant trunk (FET) technique has become an important tool in the treatment of acute type A aortic dissection. The aim of this study was to evaluate the effect of long FET on spinal cord injury (SCI) and distal aortic remodeling after acute type A aortic dissection based on clinical and radiological outcomes.

Methods: From January 2018 to November 2019, 158 patients (mean age 51.8 years [range: 32-78 years], 88.6% male) with acute type A aortic dissection were treated by FET with 100 mm (n = 113) or 150 mm (n = 45) open hybrid stent graft prosthesis. Patients were divided into two groups according to the length of FET. The clinical and radiological outcomes of the patients were reviewed retrospectively.

Results: Postoperative outcomes did not differ significantly: in-hospital mortality (9.7% vs. 6.7%, p = .758) and SCI (5.3% vs. 2.2%, p = .674). Aortic remodeling, which was evaluated by aortic diameter, true lumen diameter, false lumen (FL) diameter and the rate of FL complete thrombosis, was more positive in long FET group in the descending thoracic aorta during the follow-up period. At the abdominal level, there was no statistically significant difference between the two groups.

Conclusions: The long version of FET does not increase the risk of SCI in patients with acute type A aortic dissection. The application of long FET can achieve better results in terms of remodeling of the thoracic aorta in the short- and medium-term follow-up.
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http://dx.doi.org/10.1111/jocs.15766DOI Listing
June 2021

METTL3 promotes tumour development by decreasing APC expression mediated by APC mRNA N-methyladenosine-dependent YTHDF binding.

Nat Commun 2021 06 21;12(1):3803. Epub 2021 Jun 21.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The adenomatous polyposis coli (APC) is a frequently mutated tumour suppressor gene in cancers. However, whether APC is regulated at the epitranscriptomic level remains elusive. In this study, we analysed TCGA data and separated 200 paired oesophageal squamous cell carcinoma (ESCC) specimens and their adjacent normal tissues and demonstrated that methyltransferase-like 3 (METTL3) is highly expressed in tumour tissues. mA-RNA immunoprecipitation sequencing revealed that METTL3 upregulates the mA modification of APC, which recruits YTHDF for APC mRNA degradation. Reduced APC expression increases the expression of β-catenin and β-catenin-mediated cyclin D1, c-Myc, and PKM2 expression, thereby leading to enhanced aerobic glycolysis, ESCC cell proliferation, and tumour formation in mice. In addition, downregulated APC expression correlates with upregulated METTL3 expression in human ESCC specimens and poor prognosis in ESCC patients. Our findings reveal a mechanism by which the Wnt/β-catenin pathway is upregulated in ESCC via METTL3/YTHDF-coupled epitranscriptomal downregulation of APC.
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http://dx.doi.org/10.1038/s41467-021-23501-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217513PMC
June 2021

Metasurface-assisted broadband optical absorption in ultrathin perovskite films.

Opt Express 2021 Jun;29(12):19170-19182

Ultrathin hybrid organic-inorganic perovskite (HOIP) films have significant potential for use in integrated high-performance photoelectric devices. However, the relatively low optical absorption capabilities of thinner films, particularly in the long-wavelength region, pose a significant challenge to the further improvement of photoelectrical conversion in ultrathin HOIP films. To address this problem, we propose a combining of ultrathin HOIP film with plasmonic metasurface to enhance the absorption of the film effectively. The metasurface excites localized surface plasmon resonances and deflects the reflected light within the HOIP film, resulting in an obvious enhancement of film absorption. Finite-difference time-domain simulation results reveal that the far-field intensities, deflection angles, and electric field distributions can be effectively varied by using metasurfaces with different arrangements. Examination of the reflection and absorption spectra reveals that embedding a specifically designed metasurface into the HOIP film produces an obvious enhancement in broadband optical absorption compared with pure HOIP films. We further demonstrate that this broadband absorption promotion mechanism can be effective at a wide range of HOIP film thicknesses. Comparison of the absorption spectra at various incidence angles of ultrathin HOIP films with and without underlying metasurfaces indicates that the addition of a metasurface can effectively promote absorption under wide-angle incident light illumination. Moreover, by extending the metasurface structure to a two-dimensional case, absorption enhancements insensitive to the incident polarization states have also been demonstrated. This proposed metasurface-assisted absorption enhancement method could be applied in designing novel high-performance thin-film solar cells and photodetectors.
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http://dx.doi.org/10.1364/OE.427028DOI Listing
June 2021

Celecoxib ameliorates diabetic neuropathy by decreasing apoptosis and oxidative stress in dorsal root ganglion neurons via the miR-155/COX-2 axis.

Exp Ther Med 2021 Aug 2;22(2):825. Epub 2021 Jun 2.

Department of Neurology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.

Celecoxib (CXB) is the only clinical cyclooxygenase-2 (COX-2) inhibitor. Oral administration of CXB in experimental diabetic mice effectively relieved the symptoms of diabetic neuropathy (DN); however, the molecular mechanism remains unclear. The present study aimed to investigate the potential molecular mechanisms of CXB in the treatment of DN. An cellular model of DN was produced by stimulating dorsal root ganglion (DRG) neurons with high glucose. Cell viability and apoptosis were assessed by Cell Counting Kit-8 assays and flow cytometry, respectively. Reactive oxygen species (ROS) kits, ELISA kits and western blotting were used to determine oxidative cellular damage. The expression level of microRNA (miR)-155 was analyzed by reverse transcription-quantitative PCR. The starBase database and dual-luciferase assays were performed to predict and determine the interaction between miR-155 and COX-2. Protein expression of neurotrophic factors, oxidative stress-related proteins and COX-2 were analyzed by western blotting. Incubation with high glucose led to a decrease in DRG neuron cell viability, facilitated apoptosis, downregulated NGF and BDNF expression, increased ROS and MDA generation and decreased SOD activity. Treatment with CXB significantly protected DRG neurons against high glucose-evoked damage. CXB promoted the expression of miR-155 and COX-2 was revealed to be a direct target of miR-155. Inhibition of COX-2 enhanced the protective effect of CXB on DRG neurons and that treatment with an miR-155 inhibitor partially rescued this effect. The present study demonstrated the involvement of the miR-155/COX-2 axis in the protective effect of CXB against high glucose-induced DN.
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http://dx.doi.org/10.3892/etm.2021.10257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200812PMC
August 2021

Impacts of Reduced Nitrate Supply on Nitrogen Metabolism, Photosynthetic Light-Use Efficiency, and Nutritional Values of Edible .

Authors:
Jie He Lin Qin

Front Plant Sci 2021 4;12:686910. Epub 2021 Jun 4.

National Institute of Education, Nanyang Technological University, Singapore, Singapore.

(common ice plant), as a nutritious ready-to-eat salad in Singapore, has become popular in recent years. However, basic data about the impacts of NO supply on its NO accumulation and nutritional quality are lacking. In this study, all plants were first grown indoor hydroponically in 10% artificial seawater (ASW) with modified full-strength Netherlands Standard Composition nutrient solution for 11 days, before transferring them to different reduced NO solutions. All plants grew well and healthy after 7 days of treatment. However, plants grown with 3/4 N and 1/2 N were bigger with higher shoot and root fresh weight (FW), greater leaf number, and total leaf area (TLA) than those grown with full nitrogen (N), 1/4 N, and 0 N. grown with full N, 3/4 N, and 1/4 N had similar specific leaf area (SLA), while 0 N plants had significantly lower SLA. All plants had similar leaf succulence (LS). However, leaf water content (LWC) was lower, while leaf dry matter accumulation (LDMC) was higher in 0 N plants after 7 days of treatment. Compared with plants grown with full N, shoot NO concentrations in 3/4 N, 1/2 N, and 1/4 N plants were constant or slightly increased during the treatments. For 0 N plants, shoot NO concentration decreased significantly during the treatment compared with other plants. Shoot NO accumulation was associated with nitrate reductase activity (NRA). For instance, after 7 days of treatment, shoot NO concentration and NRA on a FW basis in 0 N plants were, respectively, 45 and 31% of full N plants. After transferring full N to 0 N for 7 days, all had higher chlorophyll (Chl) content coupled with higher electron transport rate (ETR) and higher effective quantum yield of PSII, while full N plants had higher non-photochemical quenching (NPQ). The 0N plants had much higher concentrations of proline, total soluble sugar (TSS), and total ascorbic acid (ASC) than other plants. In conclusion, totally withdrawing NO from the growth media prior to harvest could be one of the strategies to reduce shoot NO concentration. Reduced NO supply further enhanced nutritional values as concentrations of proline, TSS, and ASC were enhanced markedly in plants after transferring them from full N to 0 N.
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http://dx.doi.org/10.3389/fpls.2021.686910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213338PMC
June 2021
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