Publications by authors named "Chaoyang Li"

281 Publications

The landscape of accessible chromatin in quiescent cardiac fibroblasts and cardiac fibroblasts activated after myocardial infarction.

Epigenetics 2021 Sep 23. Epub 2021 Sep 23.

School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA.

After myocardial infarction, the massive death of cardiomyocytes leads to cardiac fibroblast proliferation and myofibroblast differentiation, which contributes to the extracellular matrix remodeling of the infarcted myocardium. We recently found that myofibroblasts further differentiate into matrifibrocytes, a newly identified cardiac fibroblast differentiation state. Cardiac fibroblasts of different states have distinct gene expression profiles closely related to their functions. However, the mechanism responsible for the gene expression changes during these activation and differentiation events is still not clear. In this study, the gene expression profiling and genome-wide accessible chromatin mapping of mouse cardiac fibroblasts isolated from the uninjured myocardium and the infarct at multiple time points corresponding to different differentiation states were performed by RNA sequencing (RNA-seq) and the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), respectively. ATAC-seq peaks were highly enriched in the promoter area and the distal area where enhancers are located. A positive correlation was identified between the expression and promoter accessibility for many dynamically expressed genes, even though evidence showed that mechanisms independent of chromatin accessibility may also contribute to the gene expression changes in cardiac fibroblasts after MI. Moreover, motif enrichment analysis and gene regulatory network construction identified transcription factors that possibly contributed to the differential gene expression between cardiac fibroblasts of different states.
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http://dx.doi.org/10.1080/15592294.2021.1982158DOI Listing
September 2021

A Robust Panel Based on Mitochondrial Localized Proteins for Prognostic Prediction of Lung Adenocarcinoma.

Oxid Med Cell Longev 2021 9;2021:7569168. Epub 2021 Sep 9.

Affiliated Cancer Hospital and Institute of Guangzhou Medical University; Key Laboratory for Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510000, China.

Due to high energy and material metabolism requirements, mitochondria are frequently active in tumor cells. Our study found that the high energy metabolism status is positively correlated with the poor prognosis of patients with lung adenocarcinoma. We constructed a scoring system (mitoRiskscore) based on the gene expression of specific mitochondrial localized proteins through univariate and LASSO cox regression. It has been shown that high mitoRiskscore was correlated with a shorter survival time after surgery in patients with lung adenocarcinoma. Compared with the typical TNM grading system, the mitoRiskscore gene panel had higher prediction accuracy. A vast number of external verification results ensured its universality. Additionally, the mitoRiskscore could evaluate the metabolic pattern and chemotherapy sensitivity of the tumor samples. Lung adenocarcinoma with higher mitoRiskscore was more active in glycolysis, and oxidative phosphorylation expression of proliferation-related pathway genes was also significantly upregulated. In contrast, patients with low mitoRiskscore had similar metabolic patterns to normal tissues. In order to improve the accuracy of prediction ability and promote clinical usage, we developed a nomogram that combined mitoRiskscore and clinical prognostic factors to predict the 3-year, 5-year, and 10-year survival rates of patients. We also performed in vitro experiments to verify the function of the key genes in the mitoRiskscore panel. In conclusion, the mitoRiskscore scoring system may assist clinicians to judge the postoperative survival rate and chemotherapy of patients with lung adenocarcinoma.
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http://dx.doi.org/10.1155/2021/7569168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445726PMC
September 2021

The mechanism of intestinal flora dysregulation mediated by intestinal bacterial biofilm to induce constipation.

Bioengineered 2021 Dec;12(1):6484-6498

Department of Gastrointestinal Surgery, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu Province, China.

To explore mechanism of intestinal flora dysregulation promoting constipation, 60 specific pathogen-free (SPF) mice were used as research objects and were treated with constipation population fecal fluid gavage and distilled water gavage. Then, relationship between intestinal dysregulation and constipation in mice with biofilm-mediated intestinal flora was investigated in vitro. The results showed that recombinant serotonin transporter (SERT) messenger ribonucleic acid (mRNA) level of the constipation population fecal fluid gavage group and the relative expression level of SERT mRNA were 1.61 ± 0.08 and 1.49 ± 0.06, which were higher markedly than those of distilled water group ( < 0.05). The level of 5-hydroxytryptamine (5-HT) in colonic tissue of the constipation population fecal fluid gavage group was 145.36 ± 14.12 ng/mL, and the expression level of 5-HT on the surface of epithelial cells of biofilm-positive colonic tissue was 20.11 ± 2.03, which were significantly lower than those of the distilled water group, with statistical significance ( < 0.05). Besides, the microbial sequencing of fecal flora indicated that The Akk and bacteroidetes ofconstipation population fecal fluid gavage group were higher hugely than those of distilled water group ( < 0.05).In conclusion, after the occurrence of constipation, the diversity of intestinal microflora decreased, and the probiotics reduced. Iintestinal microflora dysregulation would lead to increase of SERT expression level in defecation function and intestinal motility in mice, and the decrease of 5-HT, thereby changing the intestinal movement resulting in mucosal protective barrier damage,thereby causing changes in intestinal movement and the destruction of the intestinal mucosal protective barrier, which eventually resulted in constipation. The occurrence of constipation could be improved by regulating balance of intestinal flora, increasing the diversity of flora, and reducing the genus of opportunistic pathogens.
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http://dx.doi.org/10.1080/21655979.2021.1973356DOI Listing
December 2021

The relationship between core temperature and perioperative shivering during caesarean section under intrathecal anesthesia with bupivacaine and ropivacaine: a randomized controlled study.

J Anesth 2021 Sep 2. Epub 2021 Sep 2.

Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, 430022, China.

Purpose: To assess the incidence rate of perioperative shivering for cesarean section and explore the associations between the occurrence of shivering and hypothermia, core temperature change, local anesthetic.

Methods: This is a prospective, randomized, controlled, double-blinded study of 100 patients consenting for caesarean section under intrathecal anesthesia. Parturients with ASA I or II accepted elective caesarean section with combined spinal-epidural anesthesia (SA). 2-2.5 ml of 0.5% bupivacaine or 0.5% ropivacaine was intrathecally injected in group B and group R, respectively.

Results: The intraoperative shivering incidence in group B was significantly higher than that in group R (66.7 vs. 20.5%, Pvalue < 0.001), and shivering intensity in group B was significantly greater than group R (score: 1.4 vs. 0.3, Pvalue < 0.001). The core temperature in both groups gradually decreased with the time after SA. Hypothermia (core temperature < 36.0 ℃) 5-30 min after SA was not associated with shivering. However, changes of temperature at 25 and 30 min after SA, and bupivacaine were statistically associated with shivering, with the odds of 10.77 (95% CI: 1.36-85.21, P value = 0.02), 8.88 (95% CI: 1.29-60.97, P value = 0.03), and 7.78 (95% CI: 2.94-20.59, P value < 0.01), respectively.

Conclusions: In our study, for cesarean section, the occurrence of shivering was associated with the local anesthetics and the change of core temperature after SA, while not the hypothermia.
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http://dx.doi.org/10.1007/s00540-021-02995-9DOI Listing
September 2021

Non-linear Relationships Between the Built Environment and Walking Frequency Among Older Adults in Zhongshan, China.

Front Public Health 2021 5;9:686144. Epub 2021 Aug 5.

State Key Laboratory of Ocean Engineering, China Institute for Urban Governance, Shanghai Jiao Tong University, Shanghai, China.

Promoting walking activity is an effective way to improve the health of older adults. Walking frequency is a critical component of walking behavior and an essential determinant of daily walking levels. To decipher the association between the built environment and walking frequency among older adults, this study's aims are as follows: (1) to empirically test whether non-linear relationships between the two exist, and (2) to identify the thresholds of the built environment characteristics that promote walking. The walking frequency of old adults was derived from the Zhongshan Household Travel Survey (ZHTS) in 2012. The sample size of old adults aged 60 or over was 4784 from 274 urban and rural neighborhoods. A semi-parametric generalized additive model (GAMM) is used to analyze the non-linear or non-monotonic relationships between the built environment and the walking frequency among older adults. We found that non-linear relationships exist among five out of the six built environment characteristics. Within certain thresholds, the population density, sidewalk density, bus stop density, land use mixture, and the percentage of green space are positively related to older adults' walking trips. Furthermore, the land use mixture and the percentage of green space show an inverse "V"-shaped relationship. Built environment features can either support or hinder the walking frequency among older adults. The findings in the current study contribute to effective land use and transport policies for promoting active travel among older adults.
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http://dx.doi.org/10.3389/fpubh.2021.686144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374739PMC
August 2021

Oseltamivir Improved Thrombocytopenia During Veno-Arterial Extracorporeal Membrane Oxygenation in Adults With Refractory Cardiac Failure: A Single-Center Retrospective Real-World Study.

Front Cardiovasc Med 2021 26;8:645867. Epub 2021 Jul 26.

Qilu Hospital, Shandong University, Jinan, China.

Severe thrombocytopenia is a common complication of extracorporeal membrane oxygenation (ECMO). Oseltamivir can be used to treat infection-associated thrombocytopenia. To evaluate the effect of oseltamivir on attenuating severe thrombocytopenia during ECMO. This was a single-center real-world study in critically ill patients supported with venous-arterial extracorporeal membrane oxygenation (VA-ECMO). Patients suspected or confirmed with influenza received oseltamivir according to the Chinese guidelines. Thrombocytopenia and survival were compared between the oseltamivir-treated and untreated group. The factors associated with survival were analyzed by multivariable Cox analysis. A total of 82 patients were included. All patients developed thrombocytopenia after initiating VA-ECMO. Twenty-three patients received oseltamivir (O group), and 59 did not use oseltamivir (O group). During the first 8 days after VA-ECMO initiation, the platelet count in the O group was higher than that in the O group (all < 0.05). The patients in the O group had a higher median nadir platelet count (77,000/μl, 6,000-169,000/μl) compared with the O group (49,000/μl, 2,000-168,000/μl; = 0.04). A nadir platelet count of <50,000/μl was seen in 26% of the patients in the O group, compared with 53% in the O group ( = 0.031). No significant difference in survival from cardiac failure was seen between the O and O group (48 vs. 56%, = 0.508). The Sequential Organ Failure Assessment (SOFA) score on initiation of VA-ECMO were independently associated with survival (OR = 1.12, 95% confidence interval (95% CI): 1.02-1.22, = 0.015). Oseltamivir could ameliorate VA-ECMO-related thrombocytopenia. These findings suggested the prophylactic potential of oseltamivir on severe thrombocytopenia associated with the initiation of VA-ECMO.
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http://dx.doi.org/10.3389/fcvm.2021.645867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349981PMC
July 2021

Application of RR-XGBoost combined model in data calibration of micro air quality detector.

Sci Rep 2021 Aug 2;11(1):15662. Epub 2021 Aug 2.

College of Management, Henan University of Technology, Zhengzhou, 450001, China.

Grid monitoring is the current development direction of atmospheric monitoring. The micro air quality detector is of great help to the grid monitoring of the atmosphere, so higher requirements are put forward for the accuracy of the micro air quality detector. This paper presents a model to calibrate the measurement data of the micro air quality detector using the monitoring data of the air quality monitoring station. The concentration of six types of air pollutants is the research object of this study to establish a calibration model for the measurement data of the micro air quality detector. The first step is to use correlation analysis to find out the main factors affecting the concentration of the six types of pollutants. The second step uses Ridge Regression (RR) to select variables, find out the factors that have significant effects on the concentration of pollutants, and give the quantitative relationship between these factors and the pollutants. Finally, the predicted value of the ridge regression model and the measurement data of the micro air quality detector are used as input variables, and the Extreme Gradient Boosting (XGBoost) algorithm is used to give the final pollutant concentration prediction model. We named the combined model of ridge regression and XGBoost algorithm RR-XGBoost model. Relative Mean Absolute Percent Error (MAPE), Mean Absolute Error (MAE), goodness of fit (R), and Root Mean Square Error (RMSE) were used to evaluate the prediction accuracy of the RR-XGBoost model. The results show that the model is superior to some commonly used pollutant prediction methods such as random forest, support vector machine, and multilayer perceptron neural network in the evaluation of various indicators. The model not only has a good prediction effect on the training set but also on the test set, indicating that the model has good generalization ability. Using the RR-XGBoost model to calibrate the data of the micro air quality detector can make up for the shortcomings of the data monitoring accuracy of the micro air quality detector. The model plays an active role in the deployment of micro air quality detectors and grid monitoring of the atmosphere.
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http://dx.doi.org/10.1038/s41598-021-95027-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329182PMC
August 2021

Predictive Value of High ICAM-1 Level for Poor Treatment Response to Low-Dose Decitabine in Adult Corticosteroid Resistant ITP Patients.

Front Immunol 2021 13;12:689663. Epub 2021 Jul 13.

Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Primary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease. Endothelial cell activation/injury has been found in some autoimmune diseases including SLE, systemic sclerosis, and rheumatoid arthritis, but its role in ITP pathogenesis remains unclear. This study attempted to elucidate the correlation between endothelial dysfunction and disease severity of ITP and find related markers to predict response to low-dose decitabine treatment. Compared with healthy volunteers, higher plasma levels of soluble intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), and Angiopoietin-2 were found in adult corticosteroid resistant ITP patients. Notably, ICAM-1 levels were negatively correlated with the platelet count, and positively associated with the bleeding score. Recently, we have reported the efficacy and safety of low-dose decitabine in adult patients with ITP who failed for the first line therapies. Here, we evaluated the correlation of plasma ICAM-1 level with the efficacy of low-dose decitabine therapy for corticosteroid resistant ITP. A total of 29 adult corticosteroid resistant ITP patients who received consecutive treatments of low-dose decitabine were enrolled in this study. Fourteen patients showed response (nine showed complete response and five showed partial response). The levels of ICAM-1 before and after treatment were significantly higher in the non-responsive ITP patients than in the responsive patients. As shown in the multivariable logistic regression model, the odds of developing no-response to low-dose decitabine increased by 36.8% for per 5 ng/ml increase in plasma ICAM-1 level [odds ratio (OR) 1.368, 95% confidence interval (CI): 1.060 to 1.764]. In summary, this was the first study to elucidate the relationship between endothelial dysfunction and corticosteroid resistant ITP and identify the potential predictive value of ICAM-1 level for response to low-dose decitabine.
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http://dx.doi.org/10.3389/fimmu.2021.689663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313967PMC
July 2021

Regenerative Effects of Hypoxia Primed Flowable Placental Formulation in Muscle and Dermal Injury.

Int J Mol Sci 2021 Jul 1;22(13). Epub 2021 Jul 1.

Smith & Nephew Plc., Columbia, MD 21046, USA.

The placental tissue, due to its angiogenic, anti-inflammatory, antioxidative, antimicrobial, and anti-fibrotic properties, has become a compelling source towards a solution for several indications in regenerative medicine. However, methods to enhance and capture the therapeutic properties with formulations that can further the applications of viable placental tissue have not been explored. In this study, we investigated the regenerative effects of a hypoxia primed flowable placental formulation (FPF), composed of amnion/chorion and umbilical tissue, in two in vivo injury models. Laser Doppler data from rodent ischemia hindlimbs treated with FPF revealed significant tissue perfusion improvements compared to control ischemic hindlimbs. To further corroborate FPF's effects, we used a rodent ischemic bipedicle skin flap wound model. FPF treatment significantly increased the rate of wound closure and the quality of wound healing. FPF-treated wounds displayed reduced inflammation and an increase in angiogenesis. Furthermore, quantitative PCR and next-generation sequencing analysis confirmed these changes in the FPF-treated group at both the gene and transcriptional level. The observed modulation in miRNAs was associated with angiogenesis, regulation of inflammatory microenvironment, cell migration and apoptosis, reactive oxygen species generation, and restoring epithelial barrier function, all processes involved in impaired tissue healing. Taken together, these data validate the tissue regenerative properties of the flowable placental formulation configuration tested.
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http://dx.doi.org/10.3390/ijms22137151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267721PMC
July 2021

Prospective Statewide Study of Universal Screening for Hereditary Colorectal Cancer: The Ohio Colorectal Cancer Prevention Initiative.

JCO Precis Oncol 2021 5;5. Epub 2021 May 5.

Department of Hematology/Oncology, Licking Memorial Hospital, Newark, OH.

Hereditary cancer syndromes infer high cancer risks and require intensive surveillance. Identification of high-risk individuals among patients with colorectal cancer (CRC) needs improvement.

Methods: Three thousand three hundred ten unselected adults who underwent surgical resection for primary invasive CRC were prospectively accrued from 51 hospitals across Ohio between January 1, 2013, and December 31, 2016. Universal Tumor screening (UTS) for mismatch repair (MMR) deficiency was performed for all, and pathogenic germline variants (PGVs) were identified using multigene panel testing (MGPT) in those who met at least one inclusion criterion: MMR deficiency, diagnosed < 50 years, multiple primary tumors (CRC or endometrial cancer), or with a first-degree relative with CRC or endometrial cancer.

Results: Five hundred twenty-five patients (15.9%) had MMR deficiency. Two hundred thirty-four of 3,310 (7.1%; 16% of the 1,462 who received MGPT) had 248 PGVs in cancer susceptibility genes. One hundred forty-two (4.3%) had a PGV in an MMR gene, and 101 (3.1%) had a PGV in a non-MMR gene. Ten with Lynch syndrome (LS) also had a non-MMR PGV and were included in both groups. Two (0.06%) had constitutional hypermethylation. Of unexplained MMR-deficient patients, 88.4% (76 of 86) had double somatic MMR mutations. Testing for only MMR genes in MMR-deficient patients would have missed 18 non-MMR gene PGVs (7.3% of total PGVs identified). Had UTS been the only method used to screen for hereditary cancer syndromes, 38.6% (91 of 236) would have been missed, including 6.3% (9 of 144) of those with LS. These results have treatment implications as 5.3% (175 of 3,310) had PGVs in genes with therapeutic targets.

Conclusion: UTS alone is insufficient for identifying a large proportion of CRC patients with hereditary syndromes, including some with LS. At a minimum, 7.1% of individuals with CRC have a PGV and pan-cancer MGPT should be considered for all patients with CRC.
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http://dx.doi.org/10.1200/PO.20.00525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232834PMC
May 2021

Gold nanoparticles-mediated fluorescent chemical nose sensor for pathogenic diagnosis and phenotype.

J Mol Recognit 2021 Jun 17:e2919. Epub 2021 Jun 17.

State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, Haikou, PR China.

Pathogens are one of the important factors affecting national economic construction. An ideal detection system for pathogen control with excellent sensitivity, high specificity, and time-saving is needed. Here, we reported a method for bacterial detection using gold nanoparticles-mediated fluorescent "chemical nose" sensors (GFCEs). The technique consists of gold nanoparticles-coated magnetic particle using benzaldehyde, octyl aldehyde, and pyrimidine-4-formaldehyde modified, respectively. And these positively charged nanocompound interacting with three different fluorescent proteins (FPs) to form three kinds of GFCEs, respectively, named GFCE1, GFCE2, and GFCE3. Upon binding with pathogenic cells, functionalized gold nanoparticles could identify patches on hydrophobic/functional surfaces of microorganisms, and self-assemble with living bacteria by complementary electrostatic interactions. The binding ability between GFCEs and bacteria determines the change of fluorescence response of three FPs from GFCEs. These feature fluorescent level are pathogen-specific, highly repeatable, and can be analyzed by Linear Discriminant Analysis (LDA). The combination of GFCE1 and GFCE2 has the best performance when detecting pathogens with concentrations of 10  cfu mL . The first discriminant within 15 minutes is 93.8%, which could be used for subsequent identification of unknown samples. The commonly applicable system provides a simple way for the rapid bacterial detection without preprocessing procedures.
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http://dx.doi.org/10.1002/jmr.2919DOI Listing
June 2021

Crizotinib and Doxorubicin Cooperatively Reduces Drug Resistance by Mitigating MDR1 to Increase Hepatocellular Carcinoma Cells Death.

Front Oncol 2021 18;11:650052. Epub 2021 May 18.

State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.

As the sixth most lethal cancers worldwide, hepatocellular carcinoma (HCC) has been treated with doxorubicin (Dox) for decades. However, chemotherapy resistance, especially for Dox is an even more prominent problem due to its high cardiotoxicity. To find a regimen to reduce Dox resistance, and identify the mechanisms behind it, we tried to identify combination of drugs that can overcome drug resistance by screening tyrosine kinase inhibitor(s) with Dox with various HCC cell lines and . We report here that combination of Crizo and Dox has a synergistic effect on inducing HCC cell death. Accordingly, Crizo plus Dox increases Dox accumulation in nucleus 3-16 times compared to Dox only; HCC cell death enhanced at least 50% and tumor weights reduced ranging from 35 to 65%. Combining these two drugs reduces multiple drug resistance 1 (MDR1) protein as a result of activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), which phosphorylates eIF2α, leading to protein translational repression. Additionally, PERK stimulation activates C-Jun terminal kinase (JNK), resulting in accumulation of unfused autophagosome to enhance autophagic cell death Poly-ADP-ribosyltransferase (PARP-1) cleavage. When the activity of PERK or JNK is blocked, unfused autophagosome is diminished, cleaved PARP-1 is reduced, and cell death is abated. Therefore, Crizo plus Dox sensitize HCC drug resistance by engaging PERK-p- eIF2α-MDR1, and kill HCC cells by engaging PERK-JNK- autophagic cell death pathways. These newly discovered mechanisms of Crizo plus Dox not only provide a potential treatment for HCC but also point to an approach to overcome MDR1 related drug resistance in other cancers.
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http://dx.doi.org/10.3389/fonc.2021.650052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170002PMC
May 2021

Dietary Sources of Plasma Fatty Acids among Adults in the United States: NHANES 2009-2010.

Curr Dev Nutr 2021 May 12;5(5):nzab063. Epub 2021 Apr 12.

Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Background: Intake of fatty acids (TFAs) increases LDL cholesterol, decreases HDL cholesterol, and increases the risk of heart disease morbidity and mortality. Many food products potentially contain industrially produced or ruminant TFAs. However, little is known about the dietary sources of plasma TFA concentrations.

Objective: The objective of this study was to examine associations between foods consumed and plasma TFA concentrations using 24-h dietary recall data and plasma TFA measures among adults aged ≥20 y who participated in the NHANES 2009-2010 in the United States.

Methods: Over 4400 food products in the dietary interview data were categorized into 32 food and beverage groups/subgroups. Four major plasma TFAs (palmitelaidic acid, elaidic acid, vaccenic acid, linolelaidic acid) and the sum of the 4 TFAs (sumTFAs) were analyzed using GC-MS. Multivariable linear regression analyses were conducted to identify associations of plasma TFAs with all 32 food and beverage groups/subgroups, controlling for the potential confounding effects of 11 demographic, socioeconomic, behavioral, lifestyle, and health-related variables.

Results: Consumption of the following food groups/subgroups was significantly associated with elevated plasma TFA concentrations: cream substitutes (< 0.001 for palmitelaidic acid, elaidic acid, vaccenic acid, and sumTFAs); cakes, cookies, pastries, and pies (< 0.001 for elaidic acid, vaccenic acid, and sumTFAs; < 0.05 for linolelaidic acid); milk and milk desserts (< 0.01 for palmitelaidic acid and vaccenic acid; < 0.05 for linolelaidic acid and sumTFAs); beef/veal, lamb/goat, and venison/deer (< 0.01 for vaccenic acid; < 0.05 for sumTFAs); and butters (< 0.001 for palmitelaidic acid and vaccenic acid; < 0.05 for sumTFAs).

Conclusions: The findings suggest that the above 5 food groups/subgroups could be the main dietary sources of plasma TFAs among adults in the United States in 2009-2010.
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http://dx.doi.org/10.1093/cdn/nzab063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128720PMC
May 2021

Collagen prolyl 4-hydroxylases modify tumor progression.

Acta Biochim Biophys Sin (Shanghai) 2021 Jul;53(7):805-814

Affiliated Cancer Hospital & Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou 510095, China.

Collagen is the main component of the extracellular matrix. Hydroxylation of proline residues on collagen, catalyzed by collagen prolyl 4-hydroxylase (C-P4H), is essential for the stability of the collagen triple helix. Vertebrate C-P4H is an α2β2 tetramer with three isoenzymes differing in the catalytic α-subunits, which are encoded by P4HA1, P4HA2, and P4HA3 genes. In contrast, β-subunit is encoded by a single gene P4HB. The expressions of P4HAs and P4HB are regulated by multiple cellular factors, including cytokines, transcription factors, and microRNAs. P4HAs and P4HB are highly expressed in many tumors and participate in cancer progression. Several inhibitors of P4HAs and P4HB have been confirmed to have anti-tumor effects, suggesting that targeting C-P4H is a feasible strategy for cancer treatment. Here, we summarize recent progresses on the function and expression of regulatory mechanisms of C-P4H in cancer progression and point out the potential development of therapeutic strategies in targeting C-P4H in the future.
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http://dx.doi.org/10.1093/abbs/gmab065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445723PMC
July 2021

Social support and coping style of Tongqi in China: A cross-sectional study.

Arch Psychiatr Nurs 2021 06 19;35(3):317-322. Epub 2020 Dec 19.

College of Nursing, Hubei University of Chinese Medicine, Wuhan, China. Electronic address:

Tongqi (gays' wives) in China were under tremendous distress and social pressure due to their special identities and were not clearly known. A sample of 179 Chinese Tongqi were recruited through online social media groups in 2017-2018. Their hidden lives, social support, and coping styles were analyzed. The results showed that the majority of Tongqi concealed their identities, had negative responses to cope with their tremendous distress, and did not have sufficient social support. Their social support was mainly from family members. Hidden identities obstructed Tongqi's access to extrafamilial social support that could alleviate their distress. Tongqi need more social support and protection.
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http://dx.doi.org/10.1016/j.apnu.2020.12.002DOI Listing
June 2021

Combining tag-specific primer extension and magneto-DNA system for Cas14a-based universal bacterial diagnostic platform.

Biosens Bioelectron 2021 Aug 23;185:113262. Epub 2021 Apr 23.

Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing, 100084, China.

Nucleic acid-based diagnosis using CRISPR-Cas associated enzymes is essential for rapid infectious disease diagnosis and treatment strategies during a global pandemic. The obstacle has been blossomed CRIPSR-Cas based tools that can monitor wide range of pathogens in clinical samples with ultralow concentrations. Here, a universal nucleic acid magneto-DNA nanoparticle system was exploited for the detection of pathogenic bacteria, based on the collateral cleavage activity of CRISPR-Cas14a and tag-specific primer extension. In the system, the target nucleic acids were amplificated and be separated from mixtures by streptavidin-coated magnetic bead. The collateral cleavage activity of CRISPR-Cas14a can be activated via the tag sequence on the target product. Consequently, the fluorophore quencher reporter can be activated by CRISPR-Cas14a, leading to the increasing response. The exploited universal bacterial diagnostic can distinguish six different bacteria strains with 1 cfu/mL or 1 aM sensitivity, which may provide new strategies to construct fast, accurate, cost-effective and sensitive diagnostic tools in environments with limited resources.
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http://dx.doi.org/10.1016/j.bios.2021.113262DOI Listing
August 2021

Tumor Microenvironmental Competitive Endogenous RNA Network and Immune Cells Act as Robust Prognostic Predictor of Acute Myeloid Leukemia.

Front Oncol 2021 9;11:584884. Epub 2021 Apr 9.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Acute myeloid leukemia (AML) is malignant hematologic tumors with frequent recurrence and cause high mortality. Its fate is determined by abnormal intracellular competitive endogenous RNA (ceRNA) network and extracellular tumor microenvironment (TME). This study aims to build a ceRNA network related to AML TME to explore new prognostic and therapeutic targets. The RNA expression data of AML were obtained from The Cancer Genome Atlas (TCGA) database. First, we used the ESTIMATE algorithm to calculate the immune cells and stromal cells infiltration scores in the TME and found that all scores were highly correlated with AML's prognostic characteristics. Subsequently, differentially expressed mRNAs and lncRNAs between high and low score groups were identified to construct a TME-related ceRNA network. Further, the Cox-lasso survival model was employed to screen out the hub prognostic ceRNA network composed of two mRNAs (EPB41L3, COL2A1), three miRNAs (hsa-mir-26a-5p, hsa-mir-148b-3p, hsa-mir-148a-3p), and two lncRNAs (CYP1B1-AS1, C9orf106), and construct nomograms. Finally, we used CIBERSORT algorithm and Kaplan-Meier survival analysis to identify the prognostic TME immune cells and found that naive B cells, M2-type macrophages, and helper follicular T cells were related to prognosis, and the hub ceRNAs were highly correlated with immune cell infiltration. This study provided a new perspective to elucidate how TME regulates AML process and put forward the new therapy strategies combining targeting tumor cells with disintegrating TME.
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http://dx.doi.org/10.3389/fonc.2021.584884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063692PMC
April 2021

Antihuman CD44 antibody BJ18 inhibits platelet phagocytosis by correcting aberrant FcɣR expression and M1 polarization in immune thrombocytopenia.

Int Immunopharmacol 2021 Jun 6;95:107502. Epub 2021 Mar 6.

Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, China. Electronic address:

Background: Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease with a low platelet count. CD44 is a pivotal component involved in phagocytosis and inflammation, and monoclonal antibodies (mAbs) against CD44 have been shown to be beneficial in several autoimmune diseases. In the present study, we investigated the correlation between CD44 levels and disease severity in patients with ITP and explored the immunomodulatory mechanisms of the antihuman CD44 mAb BJ18 on platelet phagocytosis mediated by monocytes/macrophages.

Methods: Plasma was collected from 45 participants to measure the circulating concentration of CD44 using ELISA. Peripheral blood mononuclear cells from patients and controls were isolated and induced to differentiate into monocytes/macrophages utilizing cytokines and drugs. CD44 expression on circulating cells and the effects of BJ18 on platelet phagocytosis, Fcɣ receptor (FcɣR) expression and M1/M2 polarization of macrophages were evaluated using flow cytometry and qPCR.

Results: CD44 levels of both the soluble form found in plasma and the form expressed on the surface of circulating monocytes/macrophages were significantly elevated in ITP patients. Linear correlations were verified between the CD44 levels and major clinical characteristics. In an in vitro study, BJ18 successfully inhibited platelet phagocytosis by monocytes/macrophages obtained from ITP patients. Further studies indicated that BJ18 corrected abnormal FcγR expression on monocytes/macrophages. Moreover, the polarization of proinflammatory M1 macrophages could also be regulated by BJ18.

Conclusions: Our data indicated that the CD44 level has potential predictive value for disease severity and that the antihuman CD44 mAb BJ18 may be a promising therapy for ITP patients.
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http://dx.doi.org/10.1016/j.intimp.2021.107502DOI Listing
June 2021

Comprehensive Comparison of Amnion Stromal Cells and Chorion Stromal Cells by RNA-Seq.

Int J Mol Sci 2021 Feb 14;22(4). Epub 2021 Feb 14.

Smith and Nephew Inc., 7015 Albert Einstein Drive, Columbia, MD 21046, USA.

Mesenchymal stromal cells derived from the fetal placenta, composed of an amnion membrane, chorion membrane, and umbilical cord, have emerged as promising sources for regenerative medicine. Here, we used next-generation sequencing technology to comprehensively compare amniotic stromal cells (ASCs) with chorionic stromal cells (CSCs) at the molecular and signaling levels. Principal component analysis showed a clear dichotomy of gene expression profiles between ASCs and CSCs. Unsupervised hierarchical clustering confirmed that the biological repeats of ASCs and CSCs were able to respectively group together. Supervised analysis identified differentially expressed genes, such as , , and , and differentially expressed isoforms, such as and . Gene Ontology (GO) analysis showed that the GO terms of the extracellular matrix, angiogenesis, and cell adhesion were significantly enriched in CSCs. We further explored the factors associated with inflammation and angiogenesis using a multiplex assay. In comparison with ASCs, CSCs secreted higher levels of angiogenic factors, including angiogenin, VEGFA, HGF, and bFGF. The results of a tube formation assay proved that CSCs exhibited a strong angiogenic function. However, ASCs secreted two-fold more of an anti-inflammatory factor, TSG-6, than CSCs. In conclusion, our study demonstrated the differential gene expression patterns between ASCs and CSCs. CSCs have superior angiogenic potential, whereas ASCs exhibit increased anti-inflammatory properties.
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http://dx.doi.org/10.3390/ijms22041901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918623PMC
February 2021

Exosomes Secreted from Amniotic Membrane Contribute to Its Anti-Fibrotic Activity.

Int J Mol Sci 2021 Feb 19;22(4). Epub 2021 Feb 19.

Laboratory for Biomaterials Research, Department of Chemistry and Chemical Biology, Rutgers University, 145 Bevier Rd., Piscataway, NJ 08854, USA.

Amniotic membranes (AM) have anti-fibrotic activity. Exosomes (nano-sized vesicles) function as conduits for intercellular transfer and contain all the necessary components to induce the resolution of fibrosis. In this study, we tested the hypothesis that the anti-fibrotic activity of AM is mediated by exosomes. AM-derived exosomes or amniotic stromal cell-derived exosomes were isolated and characterized. Anti-fibrotic activity of exosomes was evaluated using human hepatic stellate cells (LX-2), an in vitro model of fibrosis. Exosomes isolated from AM tissue-conditioned media had an average size of 75 nm. Exosomes significantly inhibited the proliferation of TGFβ1-activated LX-2 but had no effect on the proliferation of non-activated LX-2 cells. Exosomes also reduced the migration of LX-2 in a scratch wound assay. Furthermore, exosomes reduced the gene expression of pro-fibrotic markers such as COL1A1, ACTA, and TGFβ1 in LX-2 cells. Interestingly, exosomes isolated from AM tissue under hypoxic conditions seemed to show a stronger anti-fibrotic activity than exosomes isolated from tissue under normoxic conditions. Exosomes released by in vitro cultured AM stromal cells were smaller in size compared with tissue exosomes and also showed anti-fibrotic activity on LX-2 cells. In conclusion, AM-tissue-released exosomes contribute to the anti-fibrotic activity of AM. This is the first report of isolation, characterization, and functional evaluation of exosomes derived from amniotic tissues with the direct comparison between tissue-derived exosomes and cultured cell-derived exosomes.
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http://dx.doi.org/10.3390/ijms22042055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922650PMC
February 2021

Engineering Extracellular Matrix Proteins to Enhance Cardiac Regeneration After Myocardial Infarction.

Front Bioeng Biotechnol 2020 20;8:611936. Epub 2021 Jan 20.

Department of Biological Engineering, Louisiana State University, Baton Rouge, LA, United States.

Engineering microenvironments for accelerated myocardial repair is a challenging goal. Cell therapy has evolved over a few decades to engraft therapeutic cells to replenish lost cardiomyocytes in the left ventricle. However, compelling evidence supports that tailoring specific signals to endogenous cells rather than the direct integration of therapeutic cells could be an attractive strategy for better clinical outcomes. Of many possible routes to instruct endogenous cells, we reviewed recent cases that extracellular matrix (ECM) proteins contribute to enhanced cardiomyocyte proliferation from neonates to adults. In addition, the presence of ECM proteins exerts biophysical regulation in tissue, leading to the control of microenvironments and adaptation for enhanced cardiomyocyte proliferation. Finally, we also summarized recent clinical trials exclusively using ECM proteins, further supporting the notion that engineering ECM proteins would be a critical strategy to enhance myocardial repair without taking any risks or complications of applying therapeutic cardiac cells.
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http://dx.doi.org/10.3389/fbioe.2020.611936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855456PMC
January 2021

Application of combined model of stepwise regression analysis and artificial neural network in data calibration of miniature air quality detector.

Sci Rep 2021 Feb 5;11(1):3247. Epub 2021 Feb 5.

College of Management, Henan University of Technology, Zhengzhou, 450001, China.

In this paper, six types of air pollutant concentrations are taken as the research object, and the data monitored by the micro air quality detector are calibrated by the national control point measurement data. We use correlation analysis to find out the main factors affecting air quality, and then build a stepwise regression model for six types of pollutants based on 8 months of data. Taking the stepwise regression fitting value and the data monitored by the miniature air quality detector as input variables, combined with the multilayer perceptron neural network, the SRA-MLP model was obtained to correct the pollutant data. We compared the stepwise regression model, the standard multilayer perceptron neural network and the SRA-MLP model by three indicators. Whether it is root mean square error, average absolute error or average relative error, SRA-MLP model is the best model. Using the SRA-MLP model to correct the data can increase the accuracy of the self-built point data by 42.5% to 86.5%. The SRA-MLP model has excellent prediction effects on both the training set and the test set, indicating that it has good generalization ability. This model plays a positive role in scientific arrangement and promotion of miniature air quality detectors. It can be applied not only to air quality monitoring, but also to the monitoring of other environmental indicators.
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http://dx.doi.org/10.1038/s41598-021-82871-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865048PMC
February 2021

Common Genes Involved in Autophagy, Cellular Senescence and the Inflammatory Response in AMD and Drug Discovery Identified via Biomedical Databases.

Transl Vis Sci Technol 2021 01 8;10(1):14. Epub 2021 Jan 8.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Purpose: Retinal pigment epithelial cell autophagy dysfunction, cellular senescence, and the retinal inflammatory response are key pathogenic factors in age-related macular degeneration (AMD), which has been reviewed in our previously work in 2019. This study aims to identify genes collectively involved in these three biological processes and target drugs in AMD.

Methods: The pubmed2ensembl database was used to perform text mining. The GeneCodis database was applied to analyze gene ontology biological process and the KEGG pathway. The STRING database was used to analyze protein-protein interaction analysis and hub genes were identified by the Cytoscape software. The Drug Gene Interaction Database was used to perform drug-gene interactions.

Results: We identified 62 genes collectively involved in AMD, autophagy, cellular senescence, and inflammatory response, 19 biological processes including 42 genes, 11 enriched KEGG pathways including 37 genes, and 12 hub genes step by step via the above biomedical databases. Finally, five hub genes (IL-6, VEGF-A, TP53, IL-1β, and transforming growth factor [TGF]-β1) and their specific interaction modes were identified, corresponding with 24 target drugs with therapeutic potential for AMD.

Conclusions: IL-6, VEGF-A, TP53, IL-1β, and TGF-β1 are pivotal in autophagy, cellular senescence, and the inflammatory response in AMD, corresponding with 24 drugs with therapeutic potential for AMD, providing definite molecular mechanisms for further research and new possibilities for AMD treatment in the future.

Translational Relevance: IL-6, VEGF-A, TP53, IL-1β, and TGF-β1 may be new targets for AMD gene therapy and drug development.
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http://dx.doi.org/10.1167/tvst.10.1.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804500PMC
January 2021

Analysis and prediction of air quality in Nanjing from autumn 2018 to summer 2019 using PCR-SVR-ARMA combined model.

Sci Rep 2021 01 11;11(1):348. Epub 2021 Jan 11.

College of Management, Henan University of Technology, Zhengzhou, 450001, China.

In order to correct the monitoring data of the miniature air quality detector, an air quality prediction model fusing Principal Component Regression (PCR), Support Vector Regression (SVR) machine, and Autoregressive Moving Average (ARMA) model was proposed to improve the prediction accuracy of the six types of pollutants in the air. First, the main information of factors affecting air quality is extracted by principal component analysis, and then principal component regression is used to give the predicted values of six types of pollutants. Second, the support vector regression machine is used to regress the predicted value of principal component regression and various influencing factors. Finally, the autoregressive moving average model is used to correct the residual items, and finally the predicted values of six types of pollutants are obtained. The experimental results showed that the proposed combination prediction model of PCR-SVR-ARMA had a better prediction effect than the artificial neural network, the standard support vector regression machine, the principal component regression, and PCR-SVR method. The Root Mean Square Error (RMSE), Mean Absolute Error (MAE), and relative Mean Absolute Percent Error (MAPE) are used as evaluation indicators to evaluate the PCR-SVR-ARMA model. This model can increase the accuracy of self-built points by 72.6% to 93.2%, and the model has excellent prediction effects in the training set and detection set, indicating that the model has good generalization ability. This model can play an active role scientific arrangement and promotion of miniature air quality detectors and grid-based monitoring of the concentration of various pollutants.
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http://dx.doi.org/10.1038/s41598-020-79462-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801597PMC
January 2021

Botulinum toxin as an ultrasensitive reporter for bacterial and SARS-CoV-2 nucleic acid diagnostics.

Biosens Bioelectron 2021 Mar 31;176:112953. Epub 2020 Dec 31.

Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing, 100084, China.

The rapid identification of pathogenic microorganisms plays a crucial role in the timely diagnosis and treatment strategies during a global pandemic, especially in resource-limited area. Herein, we present a sensitive biosensor strategy depended on botulinum neurotoxin type A light chain (BoNT/A LC) activated complex assay (BACA). BoNT/A LC, the surrogate of BoNT/A which embodying the most potent biological poisons, could serve as an ultrasensitive signal reporter with high signal-to-noise ratio to avoid common strong background response, poor stability and low intensity of current biosensor methods. A nanoparticle hybridization system, involving specific binding probes that recognize pathogenic 16S rRNAs or SARS-CoV-2 gene site, was developed to measure double-stranded biotinylated target DNA containing a single-stranded overhang using Fluorescence Resonance Energy Transfer (FRET)-based assay and colorimetric method. The method is validated widely by six different bacteria strains and severe acute respiratory related coronavirus 2 (SARS-CoV-2) nucleic acid, demonstrating a single cell or 1 aM nucleic acid detecting sensitivity. This detection strategy offers a solution for general applications and has a great prospect to be a simple instrument-free colorimetric tool, especially when facing public health emergency.
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http://dx.doi.org/10.1016/j.bios.2020.112953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836976PMC
March 2021

Fluorescent and Opt-Electric Recording Bacterial Identification Device for Ultrasensitive and Specific Detection of Microbials.

ACS Sens 2021 02 28;6(2):443-449. Epub 2020 Dec 28.

Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.

Since microbial detection is an important aspect for the prevention and control of foodborne diseases, an ideal detection system with high sensitivity, strong specificity, and timeliness is needed. Here, we proposed a fluorescent and opt-electric recording bacterial identification device (FORBID) for fully automatic real-time photoelectric sensing analysis of microbials by integrating the metabolic characteristics of microbial and selective substrate catalysis. It simplifies the testing process (one-step) and decreases the need of professional technicians. Besides, the system exhibits ultrasensitive (1 CFU/mL) and specific detection (99%) in both microbials, and . More importantly, the timeliness of this system is even better than that of the traditional culture methods. It is believed that this system can be extended to the detection of other microorganisms and provide a potential alternative for the detection of pathogens.
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http://dx.doi.org/10.1021/acssensors.0c02007DOI Listing
February 2021

Reversed Senescence of Retinal Pigment Epithelial Cell by Coculture With Embryonic Stem Cell via the TGFβ and PI3K Pathways.

Front Cell Dev Biol 2020 26;8:588050. Epub 2020 Nov 26.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Retinal pigment epithelium (RPE) cellular senescence is an important etiology of age-related macular degeneration (AMD). Aging interventions based on the application of stem cells to delay cellular senescence have shown good prospects in the treatment of age-related diseases. This study aimed to investigate the potential of the embryonic stem cells (ESCs) to reverse the senescence of RPE cells and to elucidate its regulatory mechanism. The hydrogen peroxide (HO)-mediated premature and natural passage-mediated replicative senescent RPE cells were directly cocultured with ESCs. The results showed that the proliferative capacity of premature and replicative senescent RPE cells was increased, while the positive rate of senescence-associated galactosidase (SA-β-GAL) staining and levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were decreased. The positive regulatory factors of cellular senescence (p53, p21, p16) were downregulated, while the negative regulatory factors of cellular senescence (Cyclin A2, Cyclin B1, Cyclin D1) were upregulated. Furthermore, replicative senescent RPE cells entered the S and G/M phases from the G/G phase. TGFβ (TGFB1, SMAD3, ID1, ID3) and PI3K (PIK3CG, PDK1, PLK1) pathway-related genes were upregulated in premature and replicative senescent RPE cells after ESCs application, respectively. We further treated ESCs-cocultured premature and replicative senescent RPE cells with SB531542 and LY294002 to inhibit the TGFβ and PI3K pathways, respectively, and found that p53, p21 and p16 were upregulated, while Cyclin A2, Cyclin B1, Cyclin D1, TGFβ, and PI3K pathway-related genes were downregulated, accompanied by decreased proliferation and cell cycle transition and increased positive rates of SA-β-GAL staining and levels of ROS and MMP. In conclusion, we demonstrated that ESCs can effectively reverse the senescence of premature and replicative senescent RPE cells by a direct coculture way, which may be achieved by upregulating the TGFβ and PI3K pathways, respectively, providing a basis for establishing a new therapeutic option for AMD.
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http://dx.doi.org/10.3389/fcell.2020.588050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726211PMC
November 2020

Tumor Necrosis Factor α Reduces SNAP29 Dependent Autolysosome Formation to Increase Prion Protein Level and Promote Tumor Cell Migration.

Virol Sin 2021 Jun 25;36(3):458-475. Epub 2020 Nov 25.

Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.

Tumor Necrosis Factor α (TNFα) is best known as a mediator of inflammation and immunity, and also plays important roles in tumor biology. However, the role of TNFα in tumor biology is complex and not completely understood. In a human melanoma cell line, M2, and a lung carcinoma cell line, A549, TNFα up-regulates prion protein (PrP) level, and promotes tumor cell migration in a PrP dependent manner. Silencing PRNP abrogates TNFα induced tumor cell migration; this phenotype is reversed when PRNP is re-introduced. Treatment with TNFα activates nuclear factor kappa B (NF-κB) signaling, which then mitigates autophagy by reducing the expression of Forkhead Box P3 (FOXP3). Down regulation of FOXP3 reduces the transcription of synaptosome associated protein 29 (SNAP29), which is essential in the fusion of autophagosome and lysosome creating autolysosome. FOXP3 being a bona fide transcription factor for SNAP29 is confirmed in a promoter binding assay. Accordingly, silencing SNAP29 in these cell lines also up-regulates PrP, and promotes tumor cell migration without TNFα treatment. But, when SNAP29 or FOXP3 is silenced in these cells, they are no longer respond to TNFα. Thus, a reduction in autophagy is the underlying mechanism by which expression of PrP is up-regulated, and tumor cell migration is enhanced upon TNFα treatment. Disrupting the TNFα-NF-κB-FOXP3-SNAP29 signaling axis may provide a therapeutic approach to mitigate tumor cell migration.
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http://dx.doi.org/10.1007/s12250-020-00320-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257879PMC
June 2021

Immune Microenvironment Related Competitive Endogenous RNA Network as Powerful Predictors for Melanoma Prognosis Based on WGCNA Analysis.

Front Oncol 2020 27;10:577072. Epub 2020 Oct 27.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Cutaneous melanoma is the most life-threatening skin malignant tumor due to its increasing metastasis and mortality rate. The abnormal competitive endogenous RNA network promotes the development of tumors and becomes biomarkers for the prognosis of various tumors. At the same time, the tumor immune microenvironment (TIME) is of great significance for tumor outcome and prognosis. From the perspective of TIME and ceRNA network, this study aims to explain the prognostic factors of cutaneous melanoma systematically and find novel and powerful biomarkers for target therapies. We obtained the transcriptome data of cutaneous melanoma from The Cancer Genome Atlas (TCGA) database, 3 survival-related mRNAs co-expression modules and 2 survival-related lncRNAs co-expression modules were identified through weighted gene co-expression network analysis (WCGNA), and 144 prognostic miRNAs were screened out by univariate Cox proportional hazard regression. Cox regression model and Kaplan-Meier survival analysis were employed to identify 4 hub prognostic mRNAs, and the prognostic ceRNA network consisting of 7 lncRNAs, 1 miRNA and 4 mRNAs was established. After analyzing the composition and proportion of total immune cells in cutaneous melanoma microenvironment through CIBERSORT algorithm, it is found through correlation analysis that lncRNA-TUG1 in the ceRNA network was closely related to the TIME. In this study, we first established cutaneous melanoma's TIME-related ceRNA network by WGCNA. Cutaneous melanoma prognostic markers have been identified from multiple levels, which has important guiding significance for clinical diagnosis, treatment, and further scientific research on cutaneous melanoma.
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http://dx.doi.org/10.3389/fonc.2020.577072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653056PMC
October 2020

Effect of Homogenization at a Lower Pressure on Structural and Functional Properties of Soy Protein Isolate.

J Oleo Sci 2020 ;69(11):1417-1426

Heilongjiang Bayi Agricultural University.

In this paper, the effects of homogenization at low pressure (1~40 MPa) on structural and functional properties of soy protein isolates (SPI) are investigated. Homogenization at low pressure increase solubility, surface hydrophobicity, emulsification activity and foaming capacity of SPIs, these all functional properties increases and then decreases with the homogenization pressure. Whereas, emulsion stability and foaming stability of SPIs treated by homogenization initially decrease and then increase with homogenization pressure. There is a dramatic decrease in hardness, springiness and cohesiveness of homogenized SPI gels. Generally, homogenization at low pressure do not change the subunit composition of SPIs. It is observed that, when the homogenization pressure is lower than 10 MPa than there is no significant impact on structural change. The content of β-sheet decreased, while unordered structure significantly increased, when the homogenization pressure increased from 10 MPa to 20 MPa. Furthermore, the content of β-sheet increases, when the content of the other structures decreases with the increasing homogenization pressure. The maximum emission wavelength (λmax) for SPIs increases with homogenization pressure increases from 10 Mpa to 20 Mpa, which is attributed to the gradual structural unfolding exposing more hydrophobic residues in protein surface. While, the decreased λmax of SPIs treated with 20 Mpa to 40 Mpa homogenization corresponds to the protein aggregation. It can be deduced that appropriate selection of homogenization pressure is important for improving the functional properties of SPIs.
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http://dx.doi.org/10.5650/jos.ess20076DOI Listing
November 2020
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