Publications by authors named "Liyan Huang"

64 Publications

Effect of a Humanized Diet Profile on Colonization Efficiency and Gut Microbial Diversity in Human Flora-Associated Mice.

Front Nutr 2021 23;8:633738. Epub 2021 Feb 23.

College of Food Science, South China Agricultural University, Guangzhou, China.

Human flora-associated (HFA) mouse models allow us to design interventions for human disease research to test specific hypotheses and explore the complex commensal microbiome while avoiding the ethical limitations of using humans as models to directly study intestinal flora diseases. However, few studies have investigated the effect of a humanized diet profile (coarse-feed diet; CFD) on colonization efficiency and gut microbial diversity in HFA mice. We tested the colonization efficiency and gut microbial diversity in germ-free Kunming (KM) mice fed a CFD or a purified feed diet (PFD) at 1, 2, and 4 weeks. Although the colonization efficiencies differed significantly (67.50-70.00% vs. 72.69-85.96%) in the HFA mice, the colonization efficiency of the PFD-fed HFA mice (85.96%) was significantly higher than that of the CFD-fed mice (69.61%) at 2 weeks. At 4 weeks, the colonization efficiency of the PFD-fed mice (72.69%) was comparable to that of the CFD-fed mice (70.00%). Additionally, the gut microbial diversity of the CFD-fed HFA mice was similar to that of a human fecal donor. Regarding the Kyoto Encyclopedia of Genes and Genomes colonic microbiota metabolic pathways, the CFD-fed HFA mice showed more similarities to the human donor than to the PFD-fed mice in amino sugar and nucleotide sugar metabolism, biosynthesis of amino acids, carbon metabolism, purine metabolism, and phosphotransferase systems. In conclusion, the humanized diet profiles of the CFD and PFD could help establish human microbiotas in mice. Constructing HFA mouse models fed a CFD for 4 weeks may be useful in researching human-derived intestinal diseases.
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http://dx.doi.org/10.3389/fnut.2021.633738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940529PMC
February 2021

Maternal exposure to O and NO may increase the risk of newborn congenital hypothyroidism: a national data-based analysis in China.

Environ Sci Pollut Res Int 2021 Mar 2. Epub 2021 Mar 2.

Department of Obstetrics and Gynecology, Maternal & Child Health Center, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, West Yanta Road, Xi'an,, Shaanxi, 710061, People's Republic of China.

Maternal exposure to air pollution during pregnancy is associated with adverse outcomes in the offspring, but limited studies focused on the impacts of gaseous air pollution on newborn congenital hypothyroidism (CH). Therefore, a national data-based analysis was conducted to explore the association between maternal exposure to gaseous air pollution and the incidence of CH in China. Annual average exposure levels of SO, NO, CO, and O from January 1, 2014, to December 30, 2014, were acquired from the Chinese Air Quality Online Monitoring and Analysis Platform. The annual incidence of newborn CH from October 1, 2014, to September 30, 2015, was collected from the Chinese Maternal and Child Health Surveillance Network. Temperature and toxic metal in wastewater in 2014 were also collected as covariates. Maternal exposure to O and NO in 1 μg/m level increment was positively associated with newborn CH, with an OR of 1.055 (95% CI 1.011, 1.102) and 1.097 (95% CI 1.019, 1.182) after adjusting for covariates completely. Compared with the lowest level of O, maternal exposure to the 4th quartile of O was positively associated with newborn CH (OR 1.393, 95% CI 1.081, 1.794) after adjusting for covariates completely. And the 3rd and 4th quartiles of NO were associated positively with CH (OR 1.576, 95% CI 1.025, 2.424, and OR 1.553, 95% CI 0.999, 2.414, respectively) compared with the lowest level of NO. By fitting the ROC curve, 93.688 μg/m in O might be used as cutoff to predict the incidence of newborn CH in China.
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http://dx.doi.org/10.1007/s11356-021-13083-6DOI Listing
March 2021

Rhophilin-2 Upregulates Glutamine Synthetase by Stabilizing c-Myc Protein and Confers Resistance to Glutamine Deprivation in Lung Cancer.

Front Oncol 2020 20;10:571384. Epub 2021 Jan 20.

Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Introduction: RHPN2, a member of rhophilin family of rho-binding proteins, regulates actin cytoskeleton and vesicular trafficking, and promotes mesenchymal transformation in cancer. We have found that RHPN2 was significantly mutated in lung adenocarcinoma (LUAD). However, the role of RHPN2 in lung cancer is not fully understood.

Methods: In the present study, we investigated the expression of RHPN2 in 125 patients with LUAD by qRT-PCR and correlated its expression with clinical characteristics. The effects of RHPN2 on the proliferation and invasion of lung cancer cells were determined by CCK-8 and transwell assays, clonogenic assay, and xenograft mouse model. The RhoA pull down assay and Western blotting were performed to elucidate the mechanism of RNPN2 in tumorigenesis of lung cancer.

Results: RHPN2 was overexpressed in tumors from LUAD, and high levels of RHPN2 were associated with poor prognosis of LUAD patients. RHPN2 was required for proliferation and invasion of lung cancer cells. Intriguingly, overexpression of RHPN2 conferred the resistance to glutamine depletion in lung cancer cells. Mechanistic studies revealed that ectopic overexpression of RHPN2 promoted the stability of c-Myc protein phosphorylation at Ser62 and increased c-Myc target glutamine synthetase (GS). Analysis of GS expression in clinical sample showed that the expression of GS was elevated in tumor cells. Kaplan-Meier analysis revealed that high levels of GS were significantly associated with worse overall survival time of the patients with LUAD.

Conclusions: Taken together, this study suggested that RHPN2 was involved in tumorigenesis of lung cancer modulating c-Myc stability and the expression of its target GS in lung adenocarcinoma, which links RHPN2 and glutamine metabolism.
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http://dx.doi.org/10.3389/fonc.2020.571384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855701PMC
January 2021

Development and validation of nomograms for epithelial ovarian cancer: a SEER population-based, real-world study.

Future Oncol 2021 Mar 3;17(8):893-906. Epub 2021 Feb 3.

Department of Obstetrics & Gynecology, Maternal & Child Health Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China.

To develop and internally validate nomograms to predict the overall survival (OS) and the cancer-specific survival (CSS) of patients with epithelial ovarian cancer (EOC). A total of 9001 EOC patients diagnosed between 2010 and 2013 were randomly divided into the training (n = 6301) and validation (n = 2700) cohorts. Nomogram and bootstrap validation were used to assess the predictive values of the models, including discrimination, calibration and clinical benefit. In the validation cohort, the concordance statistic values were 0.733 for OS and 0.747 for CSS. Calibration plots and decision curve analyses demonstrated moderate accuracy and clinical applicability. Nomograms were user-friendly tools for guiding clinical treatment and estimating prognosis.
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http://dx.doi.org/10.2217/fon-2020-0531DOI Listing
March 2021

Clinicopathologic features and clinical outcomes of intravenous leiomyomatosis of the uterus: A case series.

Medicine (Baltimore) 2021 Jan;100(1):e24228

Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University.

Rationale: Intravenous leiomyomatosis (IVL) is a rare and special type of smooth muscle tumor originating in the uterus. It is classified as a benign disease according to its histological features but shows the behavioral characteristics of a malignant tumor. It is easily misdiagnosed and recurrent. The purpose of this study was to retrospectively analyze clinicopathological data of 25 cases of IVL in order to enhance clinicians' understanding of this rare disease.

Patient Concerns: We screened and identified 25 cases of IVL at our hospital from October 2013 to January 2020. Five patients had tumors.

Diagnoses: The diagnosis in each case was pathologically confirmed after surgical treatment.

Interventions: All patients were managed surgically. Although the surgical procedures were different, the surgical approach was geared towards achieving complete excision. Three patients received hormonal therapy with gonadotropinreleasing hormone agonists after surgery.

Outcomes: We retrospectively reviewed all medical records and analyzed the clinicopathologic features and clinical outcomes of this disease as well as the correlations between the clinical features and risk of recurrence. Neither the symptoms nor the preoperative imaging results were suggestive of IVL in any of the cases. Except for two patients who were lost to follow-up, twenty-three patients who were followed up are still alive. Three patients experienced a recurrence.

Lessons: The clinical manifestations and ultrasound images of IVL in the early stages are not typical; thus, IVL is easily misdiagnosed as uterine leiomyoma. Radiologists, pathologists, and surgeons should have a thorough understanding of IVL and a high index of vigilance for IVL in clinical practice. Surgery should always be aimed at achieving complete tumor excision. Patients with large lesions (≥7 cm) and lesions extending to the broad ligament may have an increased risk of recurrence. Early detection, diagnosis, and treatment are very important; once the diagnosis is confirmed, regular follow-ups are crucial.
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http://dx.doi.org/10.1097/MD.0000000000024228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793403PMC
January 2021

Changing trends of birth weight with maternal age: a cross-sectional study in Xi'an city of Northwestern China.

BMC Pregnancy Childbirth 2020 Nov 30;20(1):744. Epub 2020 Nov 30.

Department of Public Health and Community Medicine, Tufts University School of Medicine, Massachusetts, Boston, USA.

Background: Most studies have shown that maternal age is associated with birth weight. However, the specific relationship between each additional year of maternal age and birth weight remains unclear. The study aimed to analyze the specific association between maternal age and birth weight.

Methods: Raw data for all live births from 2015 to 2018 were obtained from the Medical Birth Registry of Xi'an, China. A total of 490,143 mother-child pairs with full-term singleton live births and the maternal age ranging from 20 to 40 years old were included in our study. Birth weight, gestational age, neonatal birth date, maternal birth date, residence and ethnicity were collected. Generalized additive model and two-piece wise linear regression model were used to analyze the specific relationships between maternal age and birth weight, risk of low birth weight, and risk of macrosomia.

Results: The relationships between maternal age and birth weight, risk of low birth weight, and risk of macrosomia were nonlinear. Birth weight increased 16.204 g per year when maternal age was less than 24 years old (95%CI: 14.323, 18.086), and increased 12.051 g per year when maternal age ranged from 24 to 34 years old (95%CI: 11.609, 12.493), then decreased 0.824 g per year (95% CI: -3.112, 1.464). The risk of low birth weight decreased with the increase of maternal age until 36 years old (OR = 0.917, 95%CI: 0.903, 0.932 when maternal age was younger than 27 years old; OR = 0.965, 95%CI: 0.955, 0.976 when maternal age ranged from 27 to 36 years old), then increased when maternal age was older than 36 years old (OR = 1.133, 95%CI: 1.026, 1.250). The risk of macrosomia increased with the increase of maternal age (OR = 1.102, 95%CI: 1.075, 1.129 when maternal age was younger than 24 years old; OR = 1.065, 95%CI: 1.060, 1.071 when maternal age ranged from 24 to 33 years old; OR = 1.029, 95%CI: 1.012, 1.046 when maternal age was older than 33 years old).

Conclusions: For women of childbearing age (20-40 years old), the threshold of maternal age on low birth weight was 36 years old, and the risk of macrosomia increased with the increase of maternal age.
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http://dx.doi.org/10.1186/s12884-020-03445-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708914PMC
November 2020

Correction: An ionic liquid-modified RGO/polyaniline composite for high-performance flexible all-solid-state supercapacitors.

Chem Commun (Camb) 2020 Oct;56(81):12255

Beijing Key Laboratory of Energy Conversion and Storage Materials, College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.

Correction for 'An ionic liquid-modified RGO/polyaniline composite for high-performance flexible all-solid-state supercapacitors' by Chang Dong et al., Chem. Commun., 2020, DOI: 10.1039/d0cc04691d.
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http://dx.doi.org/10.1039/d0cc90422hDOI Listing
October 2020

RAB31 marks and controls an ESCRT-independent exosome pathway.

Cell Res 2021 Feb 21;31(2):157-177. Epub 2020 Sep 21.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China.

Exosomes are generated within the multivesicular endosomes (MVEs) as intraluminal vesicles (ILVs) and secreted during the fusion of MVEs with the cell membrane. The mechanisms of exosome biogenesis remain poorly explored. Here we identify that RAB31 marks and controls an ESCRT-independent exosome pathway. Active RAB31, phosphorylated by epidermal growth factor receptor (EGFR), engages flotillin proteins in lipid raft microdomains to drive EGFR entry into MVEs to form ILVs, which is independent of the ESCRT (endosomal sorting complex required for transport) machinery. Active RAB31 interacts with the SPFH domain and drives ILV formation via the Flotillin domain of flotillin proteins. Meanwhile, RAB31 recruits GTPase-activating protein TBC1D2B to inactivate RAB7, thereby preventing the fusion of MVEs with lysosomes and enabling the secretion of ILVs as exosomes. These findings establish that RAB31 has dual functions in the biogenesis of exosomes: driving ILVs formation and suppressing MVEs degradation, providing an exquisite framework to better understand exosome biogenesis.
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http://dx.doi.org/10.1038/s41422-020-00409-1DOI Listing
February 2021

Impact of air pollution exposure during various periods of pregnancy on term birth weight: a large-sample, retrospective population-based cohort study.

Environ Sci Pollut Res Int 2021 Jan 11;28(3):3296-3306. Epub 2020 Sep 11.

Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA.

Previous studies have suggested that maternal exposure to air pollution might affect term birth weight. However, the conclusions are controversial. Birth data of all term newborns born in Xi'an city of Shaanxi, China, from 2015 to 2018 and whose mother lived in Xi'an during pregnancy were selected form the Birth Registry Database. And the daily air quality data of Xi'an city was collected from Chinese Air Quality Online Monitoring and Analysis Platform. Generalized additive models (GAM) and 2-level binary logistic regression models were used to estimate the effects of air pollution exposure on term birth weight, the risk term low birth weight (TLBW), and macrosomia. Finally, 321521 term newborns were selected, including 4369(1.36%) TLBW infants and 24,960 (7.76%) macrosomia. The average pollution levels of PM, PM, and NO in Xi'an city from 2015 to 2018 were higher than national limits. During the whole pregnancy, maternal exposure to PM, PM, SO, and CO all significantly reduced the term birth weight and increased the risk of TLBW. However, NO and O exposure have significantly increased the term birth weight, and O even increased the risk of macrosomia significantly. Those effects were also observed in the first and second trimesters of pregnancy. But during the third trimester, high level of air quality index (AQI) and maternal exposure to PM, PM, SO, NO, and CO increased the term birth weight and the risk of macrosomia, while O exposure was contrary to this effect. The findings suggested that prenatal exposure to air pollution might cause adverse impacts on term birth weight, and the effects varied with trimesters and pollutants, which provides further pieces of evidence for the adverse effects of air pollution exposure in heavy polluted-area on term birth weight.
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http://dx.doi.org/10.1007/s11356-020-10705-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788013PMC
January 2021

An ionic liquid-modified RGO/polyaniline composite for high-performance flexible all-solid-state supercapacitors.

Chem Commun (Camb) 2020 Oct 8;56(80):11993-11996. Epub 2020 Sep 8.

Beijing Key Laboratory of Energy Conversion and Storage Materials, College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.

An ionic liquid-modified reduced graphene oxide/polyaniline (RGO-IL/PANI) composite was synthesized successfully. The ionic liquid enlarged the interlayer distance of RGO sheets and acted as a PANI dopant to improve the orderly establishment of PANI. The supercapacitor based on RGO-IL/PANI presented outstanding energy density (24.1 W h kg at 501 W kg), good cycling stability (91.5% capacity retention after 1000 cycles) and excellent flexibility. The results demonstrated the significant potential application of the obtained RGO-IL/PANI composite as a flexible electrode for high-performance energy storage devices.
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http://dx.doi.org/10.1039/d0cc04691dDOI Listing
October 2020

Calculating the overall survival probability in patients with cervical cancer: a nomogram and decision curve analysis-based study.

BMC Cancer 2020 Sep 1;20(1):833. Epub 2020 Sep 1.

Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA.

Background: Cervical cancer has long been a common malignance troubling women. However, there are few studies developing nomogram with comprehensive factors for the prognosis of cervical cancer. Hence, we aimed to build a nomogram to calculate the overall survival (OS) probability in patients with cervical cancer.

Methods: Data of 9876 female patients in SEER database and diagnosed as cervical cancer during 2010-2015, was retrospectively analyzed. Univariate and multivariate Cox proportional hazard regression model were applied to select predicted factors and a nomogram was developed to visualize the prediction model. The nomogram was compared with the FIGO stage prediction model. Harrell's C-index, receiver operating curve, calibration plot and decision curve analysis were used to assess the discrimination, accuracy, calibration and clinical utility of the prediction models.

Result: Eleven independent prognostic variables, including age at diagnosis, race, marital status at diagnosis, grade, histology, tumor size, FIGO stage, primary site surgery, regional lymph node surgery, radiotherapy and chemotherapy, were used to build the nomogram. The C-index of the nomogram was 0.826 (95% CI: 0.818 to 0.834), which was better than that of the FIGO stage prediction model (C-index: 0.785, 95% CI: 0.776 to 0.793). Calibration plot of the nomogram was well fitted in 3-year overall OS prediction, but overfitting in 5-year OS prediction. The net benefit of the nomogram was higher than the FIGO prediction model.

Conclusion: A clinical useful nomogram for calculating the overall survival probability in cervical cancer patients was developed. It performed better than the FIGO stage prediction model and could help clinicians to choose optimal treatments and precisely predict prognosis in clinical care and research.
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http://dx.doi.org/10.1186/s12885-020-07349-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466454PMC
September 2020

The association between prenatal exposure to polycyclic aromatic hydrocarbons and birth weight: A meta-analysis.

PLoS One 2020 13;15(8):e0236708. Epub 2020 Aug 13.

Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts, United States of America.

Background: Polycyclic aromatic hydrocarbons (PAHs) are a kind of endocrine disruptors, which can enter human body by the inhalation of PAH-containing matter and the ingestion of PAH-containing foodstuffs. Studies showed that PAHs can cross the placental barrier and might cause adverse effects on the fetus.

Objectives: This meta-analysis aimed to estimate the associations between prenatal exposure to PAHs and birth weight.

Methods: Articles published in English until May 8, 2020 and reported the effects of prenatal exposure to PAHs on birth weight were searched in multiple electronic databases including PubMed, the Web of Science, EMBASE and the Cochrane Library. The included studies were divided into three groups in accordance with the measurement of PAHs exposure. Then coefficient was extracted, conversed and synthesized by random-effects meta-analysis. And risk of bias was assessed for each study.

Results: A total of 3488 citations were searched and only 11 studies were included finally after double assessment. We found that there were no association between PAH-DNA adducts in cord blood (low/high) (OR: 1.0, 95%CI: 0.97, 1.03), 1-hydroxy pyrene (1-HP) concentration in maternal urine (OR: 1.0, 95%CI: 0.97, 1.03) and prenatal maternal airborne PAHs exposure (OR: 0.97, 95%CI: 0.93, 1.01) and birth weight. However, we observed ethnicity may change the effects of PAHs exposure on birth weight.

Conclusions: There is no significant relationship between prenatal exposure to PAHs and birth weight in our meta-analysis. Further studies are still needed for determining the effects of prenatal PAHs exposure on birth weight.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236708PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425945PMC
October 2020

Definition and Risks of Cytokine Release Syndrome in 11 Critically Ill COVID-19 Patients With Pneumonia: Analysis of Disease Characteristics.

J Infect Dis 2020 10;222(9):1444-1451

Guangzhou Respiratory Health Research Institute, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Diseases, Guangdong, China.

Corona virus disease 2019 (COVID-19) patients with severe immune abnormalities are at risk of cytokine release syndrome (CRS). The definition, prevention, and treatment of symptoms of CRS in critically ill patients with COVID-19 are important problems. We report a single-center case series of 11 COVID-19 patients with acute respiratory distress syndrome from The First Affiliated Hospital of Guangzhou Medical University in China from 26 January 2020 to 18 February 2020. The termination date of follow-up was 19 February 2020. Eight patients were determined to have characteristics of CRS, including pulmonary inflammation, fever, and dysfunction of nonpulmonary organs. An increase in interleukin-6 in peripheral blood was the highest risk factor and an early indicator of CRS in COVID-19.
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http://dx.doi.org/10.1093/infdis/jiaa387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337810PMC
October 2020

The Association between Leukocyte and Its Subtypes and Benign Breast Disease: The TCLSIH Cohort Study.

J Oncol 2020 31;2020:3560593. Epub 2020 May 31.

Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.

Inflammation plays a crucial role in the formation of benign breast disease. Given the limited study to explore the association between leukocyte as an indicator of immune system and benign breast disease, we used data from a large cross-sectional study to investigate association between leukocyte and its subtypes and benign breast disease among women in the general population. The data were derived from baseline data of the Tianjin chronic low-grade systemic inflammation and health (TCLSIH) cohort study during 2014 and 2016. Breast thickness and nodules status were assessed by using ultrasonography. Leukocyte and its subtype counts were carried out using the automated hematology analyzer. Multiple logistic regression analysis was used to examine the association between leukocyte and its subtypes and prevalence of benign breast disease. In the present study, the prevalence of benign breast disease was 20.9%. After adjustments for potentially confounding factors, the odds ratios (95% confidence interval) for benign breast disease across lymphocyte quintiles were as follows: 1.00 (reference), 0.99 (0.82, 1.2), 0.85 (0.69, 1.04), 0.84 (0.68, 1.02), and 0.75 (0.61, 0.92) ( for trend = 0.002). An inverse association between lymphocyte counts and benign breast disease was found, but leukocyte and other subtypes have nothing to do with benign breast disease. Further prospective studies are needed to determine the findings.
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http://dx.doi.org/10.1155/2020/3560593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281813PMC
May 2020

Effects of prenatal exposure to NO on children's neurodevelopment: a systematic review and meta-analysis.

Environ Sci Pollut Res Int 2020 Jul 30;27(20):24786-24798. Epub 2020 Apr 30.

Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA.

The neurotoxicity of NO exposure is well-known and potentially causes impaired of neural functions. This review aimed to estimate associations between prenatal NO exposure and neurodevelopment for children. Articles published until May 2019 reported prenatal NO exposure and children's cognition, psychomotor, language, attention, IQ, and behavior function were searched according to all related terms. The main databases we retrieved included PubMed, Web of Science, Embase, and Cochrane Library. Coefficient was extracted, conversed, and synthesized by random effects meta-analysis. Meanwhile, qualitatively describe would be used for some studies which cannot be synthesized quantitatively for lack of quantity or methods inconsistency. Finally, a total of 3848 citations were searched, and only 10 studies were included. We estimated that per 10 μg/m increase of NO during pregnancy was associated with a - 0.76 point decrease in global psychomotor (95% CI, - 1.34, - 0.18) and a - 0.62 point decrease in fine psychomotor for children (95% CI, - 1.09, - 0.16). But no significant association found in general cognitive and language. In addition, through the literature review, it seemed that prenatal exposure to NO might cause adverse impacts on children's attention, IQ, and different behaviors, but this requires confirmation from further researches. Our study indicated that prenatal exposure to NO seems to be associated with impaired neural development for children, especially for fine psychomotor. However, further studies are needed for determining the effects of prenatal air pollution exposure on attention, IQ, and behavior.
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http://dx.doi.org/10.1007/s11356-020-08832-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329770PMC
July 2020

Genetic alteration profile of -mutant resected IIB-IIIA stage NSCLC and correlation to clinical outcomes.

Transl Lung Cancer Res 2019 Dec;8(6):838-846

Department of Thoracic Oncology, State Key Laboratory of Respiratory Diseases, National Clinical Research Center of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.

Background: Genetic alteration profile of epidermal growth factor receptor () mutant resected non-small cell lung cancer (NSCLC) and its relationship with clinical outcomes remains to be illustrated and genetic biomarkers that can predict recurrence need to be figured out.

Methods: Clinicopathological and follow-up information were collected for 99 -mutant resected NSCLC. Tumor sections were collected for genetic alteration detection. Targeted next-generation sequencing (NGS) was performed to detect somatic mutations within each sample using a 285-gene panel on the Ion Torrent platform.

Results: Concurrent driver gene mutations were detected in 86 participants. Adjuvant therapy was a positive factor in disease-free survival (DFS) period, and patients receiving tyrosine kinase inhibitors (TKIs) gained the longest DFS. A total of 34 concurrent mutant driver genes were found. The median number of mutated driver genes for each sample was 2 (range, 0-12). and were the most frequent concurrent mutant driver genes with rates of 53.54% and 25.25% respectively. The number of concurrent mutant genes did not have a significant effect on recurrence. Multivariable analysis found that mutations of (P=0.021), (P=0.002), (P<0.001), (P=0.015), (P=0.042), (P=0.006), and wildtype (P=0.032), (P=0.012), (P=0.035) were independent risk factors for the recurrence of resected mutant NSCLC.

Conclusions: and was the most common concurrent mutant driver gene. Mutations of , and wildtype were independent risk factors for the recurrence of resected mutant NSCLC.
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http://dx.doi.org/10.21037/tlcr.2019.10.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976375PMC
December 2019

An Efficient Ring-Closure Method for Preparing Well-Defined Cyclic Polynorbornenes.

Macromol Rapid Commun 2020 Feb 27;41(4):e1900598. Epub 2019 Dec 27.

State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, The Chinese Academy of Sciences, Beijing, 100190, China.

An efficient bimolecular ring-closure method is developed to prepare the well-defined cyclic polynorbornenes by combining the living ring-opening metathesis polymerization (ROMP) with the self-accelerating double strain-promoted azide-alkyne cycloaddition (DSPAAC) reaction. In this method, ROMP is used to synthesize the well-defined linear polynorbornenes with both azide terminals by virtue of a N-hydroxysuccinimide-ester-functionalized Grubbs initiator following the modification of polymer end groups. DSPAAC click reaction is then used to ring-close the linear polymer precursors and prepare the corresponding well-defined cyclic polynorbornenes using the sym-dibenzo-1,5-cyclooctadiene-3,7-diyne (DIBOD) as small linkers. The self-accelerating DSPAAC ring-closing reaction facilitates this method to efficiently prepare pure cyclic polynorbornenes in the presence of a molar excess of DIBOD small linkers to the linear polynorbornene precursors. This is the first report to prepare well-defined polynorbornenes with cyclic topology based on the ring-closure strategy for cyclic polymers.
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http://dx.doi.org/10.1002/marc.201900598DOI Listing
February 2020

Chemotherapeutic drugs stimulate the release and recycling of extracellular vesicles to assist cancer cells in developing an urgent chemoresistance.

Mol Cancer 2019 12 12;18(1):182. Epub 2019 Dec 12.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.

Background: Chemotherapy is a widely used treatment for cancer. However, the development of acquired multidrug resistance (MDR) is a serious issue. Emerging evidence has shown that the extracellular vesicles (EVs) mediate MDR, but the underlying mechanism remains unclear, especially the effects of chemotherapeutic agents on this process.

Methods: Extracellular vesicles isolation was performed by differential centrifugation. The recipient cells that acquired ATP-binding cassette sub-family B member 1 (ABCB1) proteins were sorted out from co-cultures according to a stringent multi-parameter gating strategy by fluorescence-activated cell sorting (FACS). The transfer rate of ABCB1 was measured by flow cytometry. The xenograft tumor models in mice were established to evaluate the transfer of ABCB1 in vivo. Gene expression was detected by real-time PCR and Western blotting.

Results: Herein, we show that a transient exposure to chemotherapeutic agents can strikingly increase Rab8B-mediated release of extracellular vesicles (EVs) containing ABCB1 from drug-resistant cells, and accelerate these EVs to circulate back onto plasma membrane of sensitive tumor cells via the down-regulation of Rab5. Therefore, intercellular ABCB1 transfer is significantly enhanced; sensitive recipient cells acquire a rapid but unsustainable resistance to evade the cytotoxicity of chemotherapeutic agents. More fascinatingly, in the xenograft tumor models, chemotherapeutical drugs also locally or distantly increase the transfer of ABCB1 molecules. Furthermore, some Non-small-cell lung carcinoma (NSCLC) patients who are undergoing primary chemotherapy have a rapid increase of ABCB1 protein in their monocytes, and this is obviously associated with poor chemotherapeutic efficacy.

Conclusions: Chemotherapeutic agents stimulate the secretion and recycling of ABCB1-enriched EVs through the dysregulation of Rab8B and Rab5, leading to a significant increase of ABCB1 intercellular transfer, thus assisting sensitive cancer cells to develop an urgent resistant phenotype. Our findings provide a new molecular mechanism of how chemotherapeutic drugs assist sensitive cancer cells in acquiring an urgent resistance.
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http://dx.doi.org/10.1186/s12943-019-1114-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907227PMC
December 2019

Maternal exposure to PM may increase the risk of congenital hypothyroidism in the offspring: a national database based study in China.

BMC Public Health 2019 Nov 19;19(1):1412. Epub 2019 Nov 19.

Department of Obstetrics and Gynecology, Maternal & Child Health Center, the First Affiliated Hospital of Xi'an Jiaotong University, No. 277, Yanta West Road. Xi'an, Shaanxi Province, 710061, Xian, People's Republic of China.

Background: Maternal exposure to air pollution is related to fetal dysplasia. However, the association between maternal exposure to air pollution and the risk of congenital hypothyroidism (CH) in the offspring is largely unknown.

Methods: We conducted a national database based study in China to explore the association between these two parameters. The incidence of CH was collected from October 1, 2014 to October 1, 2015 from the Chinese Maternal and Child Health Surveillance Network. Considering that total period of pregnancy and consequently the total period of particle exposure is approximately 10 months, average exposure levels of PM, PM and Air Quality Index (AQI) were collected from January 1, 2014 to January 1, 2015. Generalized additive model was used to evaluate the association between air pollution and the incidence of CH, and constructing receiver operating characteristic (ROC) curve was used to calculate the cut-off value.

Results: The overall incidence of CH was 4.31 per 10,000 screened newborns in China from October 1, 2014 to October 1, 2015. For every increase of 1 μg/m in the PM exposure during gestation could increase the risk of CH (adjusted OR = 1.016 per 1 μg/m change, 95% CI, 1.001-1.031). But no significant associations were found with regard to PM (adjusted OR = 1.009, 95% CI, 0.996-1.018) or AQI (adjusted OR = 1.012, 95% CI,0.998-1.026) and the risk of CH in the offspring. The cut-off value of prenatal PM exposure for predicting the risk of CH in the offspring was 61.165 μg/m.

Conclusions: The present study suggested that maternal exposure to PM may exhibit a positive association with increased risk of CH in the offspring. We also proposed a cut-off value of PM exposure that might determine reduction in the risk of CH in the offspring in highly polluted areas.
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http://dx.doi.org/10.1186/s12889-019-7790-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862828PMC
November 2019

A novel cysteine-sparing G73A mutation of NOTCH3 in a Chinese CADASIL family.

Neurogenetics 2020 01 13;21(1):39-49. Epub 2019 Nov 13.

Brain Research Institute, Qilu Hospital of Shandong University, No. 107 West Wenhua Road, Jinan, 250012, Shandong Province, China.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic disease leading to stroke and vascular dementia. CADASIL is an inherited small blood vessel disease caused by mutations in the gene encoding the neurogenic locus notch homolog protein 3 (NOTCH3). NOTCH3 is large type I membrane receptor mainly expressed in vascular smooth muscle cells and pericytes. Most identified mutations result in insert or deletion of a cysteine residue within the EGF-like repeats. To date, some cases with a cysteine-sparing mutant have been described. Genetic analysis revealed a novel mutation in NOTCH3 in a CADASIL family. Molecular analysis revealed its potential pathogenic mechanism in causing CADASIL. In this paper, we present a Chinese family with a novel cysteine-sparing mutation in exon 3 (c.218G>C, p.G73A) of the NOTCH3 gene. Family carriers of the same mutation presented with symptoms and imaging abnormalities characteristic of CADASIL. The location of glycine 73 in between C5-C6 disulfide bond of EGF-like domain 1 shows high conservation from humans to zebra fish. It has previously been suggested that the aggregate-prone property of mutant NOTCH3 contributes to a cytotoxic effect in the pathogenic mechanism underlying CADASIL. Here, we investigated the pathogenic mechanism of the new mutation in vitro using HEK293 cells transfected with either a wild-type (WT) or c.218G>C (p.G73A) NOTCH3 plasmids, and we found p.G73A NOTCH3 was more prone to form aggregation and resistant to degradation. Moreover, the p.G73A NOTCH3 compromised cell viability by promoting apoptosis. Two known CADASIL mutants R133C and R75P showed similar results with G73A mutants. Our study here identified G73A as a new mutation in NOTCH3 to cause CADASIL and revealed that the G73A mutation and two known mutants R75P and R133C decreased NOTCH3 protein turnover and induced cell death.
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http://dx.doi.org/10.1007/s10048-019-00592-3DOI Listing
January 2020

High starchy food intake may increase the risk of adverse pregnancy outcomes: a nested case-control study in the Shaanxi province of Northwestern China.

BMC Pregnancy Childbirth 2019 Oct 21;19(1):362. Epub 2019 Oct 21.

Department of Obstetrics and Gynecology, Maternal & Child Health Center, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, Yanta West Road, Xi'an, Shaanxi Province, 710061, People's Republic of China.

Background: There was a wider disparity in the diet characterization among most studies on diet and pregnancy outcomes in different countries, and the research in northern China is limited. Therefore, the purpose of the present study that was conducted in northwest China was to understand the dietary characteristics of periconceptional women and to explore the relationship between and specific dietary patterns with adverse pregnancy outcomes.

Methods: A nested case-control study was conducted from October 2017 to November 2018 in Shaanxi, China. Based on a prospective cohort of 368 women who were pregnant or prepared for pregnancy, 63 participants who developed the outcomes of gestational hypertension, gestational diabetes, preterm birth, low birth weight, and birth defects were included in the case group. A total of 237 healthy pregnant women were included during the same period in the control group. Dietary intake was assessed using a validated food frequency questionnaire for the three months before pregnancy and the first trimester. Information on delivery details and antenatal pregnancy complications was obtained from the hospital maternity records. Dietary patterns were derived using factor analysis. Stratified analysis was performed on the overall, single and multiple adverse pregnancy outcomes categories. Adjustment was made for sociodemographic characteristics and nutritional supplement status.

Results: Six major dietary patterns were identified. The 'starchy' dietary pattern, composed of high intake in noodle and flour products and/or rice and its products, was associated with the odds of developing of adverse pregnancy outcomes (OR: 2.324, 95% CI: 1.293-4.178). This risk remained significant following adjustment for potential confounders of maternal demographic characteristics and nutritional status (aOR: 2.337, 95% CI:1.253-4.331). Strong association were found during the first trimester of pregnancy, but showed no association during the three months before pregnancy (aOR:1.473, 95% CI: 0.682-3.234).

Conclusions: High starchy food intake was associated with adverse pregnancy outcomes, particularly during the first trimester of pregnancy. Health education focusing on periconceptional dietary patterns could be a practical strategy for preventing adverse pregnancy outcomes.
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http://dx.doi.org/10.1186/s12884-019-2524-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802140PMC
October 2019

Knowledge, attitude and practice level of women at the periconceptional period: a cross-sectional study in Shaanxi China.

BMC Pregnancy Childbirth 2019 Sep 4;19(1):326. Epub 2019 Sep 4.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.

Background: Identifying and understanding the knowledge, attitude and practice (KAP) level of women at the periconceptional period has implications for formulating and measuring the adverse pregnancy outcomes for primary prevention.

Methods: A cross-sectional study among pregestational and pregnant women was conducted in Shaanxi during 2016-2017.

Results: Among 791 participants, the average score of periconceptional healthcare knowledge awareness was 6.32 ± 1.78, whereas 28.8% of women have failed. Women who planned to or had undergone premarital and pre-pregnancy examinations accounted for 50.2, and 62.5%, respectively. Less than half (42.0%) of the women started taking folic acid (FA) before pregnancy, and only 37.9% of them took FA regularly at the right time. Multivariate analysis showed that age was the main factor influencing the Attitude and Practice level of women at the periconceptional period, and demonstrated a positive effect on the awareness of right timing of folic acid supplementation, and high rates of premarital and pre-pregnancy examinations. Also, the knowledge pass rate was increased with education level. Fewer women who have birth experience were willing to take FA consistently at the right time compared to those women without birth.

Conclusions: The women at the periconceptional period in Shaanxi lacked the total KAP level of periconceptional healthcare, especially those who live in rural areas and have less education. Government agencies should reinforce more effective primary preventive measures and policies for the prevention of adverse pregnancy outcomes.
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http://dx.doi.org/10.1186/s12884-019-2481-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727354PMC
September 2019

Regulator of calcineurin 1 is a novel RNA-binding protein to regulate neuronal apoptosis.

Mol Psychiatry 2021 Apr 27;26(4):1361-1375. Epub 2019 Aug 27.

Brain Research Institute, Qilu Hospital of Shandong University, No.107 West Wenhua Road, 250012, Jinan, Shandong Province, China.

Posttranscriptional regulation of gene expression plays an important role in the maturation, transport, stability and translation of coding and noncoding RNAs. RNA-binding protein (RBP) is a key factor of the regulation. Regulator of calcineurin 1 (RCAN1) is a multifunctional protein involved in neurodegeneration, mitochondrial dysfunction, inflammation and protein glycosylation, and plays an important role in the pathogenesis of Down syndrome and Alzheimer's disease. In this report, we discovered that RCNA1 is a novel RNA-binding protein. A 23 nucleotide sequence of adenine nucleotide translocator (ANT1) mRNA was identified as the binding motif of RCAN1. Furthermore, we found that R1SR13, as the RNA aptamer of RCAN1 identified by SELEX, blocked RCAN1-induced inhibition of the nuclear factor of activated T cells (NFAT) and NF-κB signaling pathways, and reduced neuronal apoptosis. Taken together, our results demonstrate that RCAN1 is a novel RNA-binding protein and the RNA aptamer of RCAN1 plays a neuroprotective role.
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http://dx.doi.org/10.1038/s41380-019-0487-0DOI Listing
April 2021

Poly(ionic liquid)-Modified Magnetic Janus Particles for Dye Degradation.

Langmuir 2019 Sep 23;35(35):11435-11442. Epub 2019 Aug 23.

BNU Key Lab of Environmentally Friendly and Functional Polymer Materials, Beijing Key Laboratory of Energy Conversion and Storage Materials, College of Chemistry , Beijing Normal University , Beijing 100875 , China.

The FeO@SiO paramagnetic Janus particles with phenyl groups and amino groups segmented on two different sides were fabricated by the Pickering emulsion method. Then, the poly(ionic liquid)s were selectively modified onto the amino side via in situ induced ATRP polymerization. Different anions were introduced onto the poly(ionic liquid)s region by exchanging anions to adjust the wettability of the side. Meanwhile, after the PWO anions were employed, the poly(ionic liquid)-modified FeO@SiO Janus particles can be used as a catalytic solid emulsifier and degraded water-soluble dyes with the aid of stabilizing emulsion.
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http://dx.doi.org/10.1021/acs.langmuir.9b01400DOI Listing
September 2019

Circulating CXCR3 Tfh cells positively correlate with neutralizing antibody responses in HCV-infected patients.

Sci Rep 2019 07 12;9(1):10090. Epub 2019 Jul 12.

Translational Medicine Institute, The First People's Hospital of Chenzhou, University of South China, Chenzhou, Hunan, 423000, China.

Circulating T follicular helper (cTfh) cells have been identified as counterparts of germinal center Tfh (GC Tfh) cells in humans and can support T-dependent B cell maturation and antibody production in vitro. However, the role of cTfh cells in neutralizing antibody (nAb) responses in HCV infection remains unclear. Here, we characterized the phenotype and function of cTfh cells and demonstrated the associations of cTfh cells and their subsets with nAb responses in HCV infection. A total of 38 HCV-infected individuals and 28 healthy controls were enrolled from a pool of injection drug users. The frequency and function of blood Tfh cells were analyzed by flow cytometry. The titers and breadths of serum nAbs were measured using HCV pseudo-particle neutralization assays. Herein, we report several key observations. First, HCV infection skewed cTfh toward CXCR3 cTfh cell differentiation. Second, the frequency of CXCR3 cTfh cells positively correlated with HCV nAb titers and breadths. Third, CXCR3 cTfh cells showed higher expression of Tfh-associated molecules (PD-1, ICOS, IL-21, Bcl-6) compared with CXCR3 cTfh cells from individuals with HCV infection. Coculture of cTfh cells and autologous memory B cells in vitro indicated that CXCR3 cTfh cells show a superior ability to support HCV E2-specific B cell expansion compared with CXCR3 cTfh cells from individuals with HCV infection. HCV infection skews cTfh cells toward CXCR3-biased Tfh cell differentiation, which positively correlates with the magnitude and breadth of the HCV nAb response. It is our hope that these findings will provide insights for the rational design of a nAb-based HCV vaccine.
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http://dx.doi.org/10.1038/s41598-019-46533-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626020PMC
July 2019

Elevated LAG-3 on CD4 T cells negatively correlates with neutralizing antibody response during HCV infection.

Immunol Lett 2019 08 16;212:46-52. Epub 2019 Jun 16.

Translational Medicine Institute, The First People's Hospital of Chenzhou, University of South China, Chenzhou, Hunan, 423000, China; Affiliated The First People's Hospital of Chenzhou, Southern Medical University, Chenzhou, Hunan, 423000, China. Electronic address:

Lymphocyte activation gene-3 (LAG-3), an inhibitory molecule, which has been shown co-expressed with multiple inhibitory receptors on CD8 T and natural killer (NK) cells and negatively regulates T and NK cell responses during hepatitis C virus (HCV) infection. However, whether LAG-3 is involved in the regulation of the antibody response remains unclear. This study aims to investigate the relationship of LAG-3 with neutralizing antibody (nAb) response during HCV infection. A total of 66 HCV-infected individuals and 36 sex- and age-matched healthy controls from a population of intravenous drug users were recruited. Circulating follicular helper T (cTfh) cells and LAG-3-expressing CD4 T cells, type 1 regulatory T (Tr1) cells, and regulatory T (Treg) cells were characterized by flow cytometry. Serum nAb response of HCV-infected individuals was determined using pseudoparticle neutralization assays. We found that HCV infection enhanced LAG-3 expression on CD4 T cells and exhibited regulatory T cell-like phenotype and inversely associated with the HCV nAb response. Further analysis showed that frequency of CXCR3 cTfh cells positively correlated with nAb response, however LAG-3 CD4 T cells inversely associated with CXCR3 cTfh cells. This study observed that LAG-3 CD4 T cells exhibit a regulatory cell phenotype and negatively associate with the HCV nAb response, implying that LAG-3 may be involved in the negative regulation of humoral immunity during HCV infection.
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http://dx.doi.org/10.1016/j.imlet.2019.06.003DOI Listing
August 2019

Secalonic acid D induces cell apoptosis in both sensitive and ABCG2-overexpressing multidrug resistant cancer cells through upregulating c-Jun expression.

Acta Pharm Sin B 2019 May 21;9(3):516-525. Epub 2018 Dec 21.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou 510060, China.

Secalonic acid D (SAD) could inhibit cell growth in not only sensitive cells but also multidrug resistant (MDR) cells. However, the molecular mechanisms need to be elucidated. Here, we identified that SAD possessed potent cytotoxicity in 3 pairs of MDR and their parental sensitive cells including S1-MI-80 and S1, H460/MX20 and H460, MCF-7/ADR and MCF-7 cells. Furthermore, SAD induced cell G2/M phase arrest the downregulation of cyclin B1 and the increase of CDC2 phosphorylation. Importantly, JNK pathway upregulated the expression of c-Jun in protein level and increased c-Jun phosphorylation induced by SAD, which was linked to cell apoptosis c-Jun/Src/STAT3 pathway. To investigate the mechanisms of upregulation of c-Jun protein by SAD, the mRNA expression level and degradation of c-Jun were examined. We found that SAD did not alter the mRNA level of c-Jun but inhibited its proteasome-dependent degradation. Taken together, these results implicate that SAD induces cancer cell death through c-Jun/Src/STAT3 signaling axis by inhibiting the proteasome-dependent degradation of c-Jun in both sensitive cells and ATP-binding cassette transporter sub-family G member 2 (ABCG2)-mediated MDR cells.
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http://dx.doi.org/10.1016/j.apsb.2018.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543021PMC
May 2019

SCD1 is required for EGFR-targeting cancer therapy of lung cancer via re-activation of EGFR/PI3K/AKT signals.

Cancer Cell Int 2019 18;19:103. Epub 2019 Apr 18.

1Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Research Institute of Respiratory Disease, China Key Laboratory of Respiratory Disease, National Center for Clinical Trials on Respiratory Diseases, No. 151 Yanjiangxi Road, Guangzhou, Guangdong 510120 China.

Background: Cancer cells are characterized by aberrant activation of lipid biosynthesis, producing saturated fatty acids and monounsaturated fatty acids via stearoyl-CoA desaturases (SCD) for regulating metabolic and signaling platforms. SCD1 overexpression functions as an oncogene in lung cancer and predicts a poor clinical outcome. This study aimed to investigate the role of SCD1 inhibition by EGFR inhibitor (Gefitinib)-based anti-tumor therapy of lung cancer both in vitro and in vivo.

Methods: CCK-8 assay was performed to determine cell viability. The SCD1 mRNA level was detected by qPCR. The protein levels were assessed by Western blotting. E-cadherin and N-cadherin levels were determined by immunofluorescence. Apoptosis detection was conducted by flow cytometry. Cell migration or invasion was evaluated by transwell assay. The tumor sizes and tumor volumes were calculated in nude mice by subcutaneous injection of A549 cells transfected with vector of pcDNA3.1-SCD1 or negative control. Expression of Ki-67 was detected by immunohistochemistry.

Result: SCD1 up-regulated expression was observed in lung cancer cell lines. Cells with overexpressed SCD1 had high IC50 values for Gefitinib in A549 and H1573 cell lines. Overexpression of SCD1 inhibited Gefitinib-induced apoptosis, decreased cell vitality and impaired ability of migration and invasion, while these effects were counteracted by A939572. Mechanistically, SCD1 promoted the activation of proliferation and metastasis-related EGFR/PI3K/AKT signaling, and up-regulated epithelial to mesenchymal transition (EMT) phenotype in the two cell lines, which was restored by SCD1 inhibition. Furthermore, in spite of EGFR inhibition, overexpression of SCD1 in vivo significantly promoted tumor growth by activating EGFR/PI3K/AKT signaling in tumor tissues, but A939572 treatment restricted SCD1-induced tumor progression and inhibited EMT phenotype of cancer cells in vivo.

Conclusion: These findings indicated that inhibition of oncogene SCD1 is required for targeting EGFR therapy in lung cancer.
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http://dx.doi.org/10.1186/s12935-019-0809-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472070PMC
April 2019

HBV coinfection with HCV alters circulating Tfh cell distribution and impairs HCV neutralizing antibody responses.

J Viral Hepat 2019 08 29;26(8):1002-1010. Epub 2019 Apr 29.

Translational Medicine Institute, The First People's Hospital of Chenzhou, University of South China, Chenzhou, Hunan, China.

Hepatitis C virus (HCV) and hepatitis B virus (HBV) coinfection reciprocally influences viral replication and host defence responses. This study aimed to investigate the impact of HBV coinfection on circulating T follicular helper cell (cTfh) distribution and the HCV neutralizing antibody (nAb) response. HCV neutralizing antibody responses were measured in individuals with HCV monoinfection (n = 83) and HBV/HCV coinfection (n = 78) using the HCV pseudoparticle neutralization assay. The frequencies of cTfh cells and their subsets in HCV monoinfection (n = 34) and HBV/HCV coinfection (n = 30) were analysed by flow cytometry. The correlations of clinical parameters, cTfh cells and neutralizing antibody responses were analysed. Compared with HCV monoinfection, the HBV coinfection group showed significantly lower HCV neutralizing antibody responses (P < 0.001) and a decreased frequency of circulating Th1-like Tfh cells (Tfh1) (P = 0.004). In HCV monoinfection, the frequency of the Tfh1 subset was positively correlated with HCV neutralizing antibody responses (R = 0.378, P = 0.03), but this correlation was lost under HBV/HCV coinfection (R = 0.115, P = 0.551). In contrast, the frequency of circulating Th2-like Tfh cells (Tfh2) was negatively correlated with the HCV neutralizing antibody responses (R = 0.404, P = 0.003). Further analysis showed that HBV coinfection enhanced the Tfh2 subset composition within cTfh cells (P < 0.001), which was associated with serum HBsAg in HBV/HCV coinfection (R = 0.521, P = 0.003). As expected, HBsAg also exhibited an inverse association with HCV neutralizing antibody responses in HBV/HCV coinfection (R = 0.59, P < 0.001). In contrast to HCV monoinfection, HBV/HCV coinfection leads to altered cTfh cell distribution and impaired HCV neutralizing antibody responses, which are associated with HBsAg. These findings will be helpful for better understanding the immunopathogenesis of HBV/HCV coinfection.
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http://dx.doi.org/10.1111/jvh.13106DOI Listing
August 2019

A cupin domain is involved in α-amylase inhibitory activity.

Plant Sci 2018 Dec 6;277:285-295. Epub 2018 Oct 6.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing 210095, China; Desert Research Institute in the Arid Region, Xinjiang Agricultural University, Urumqi 830052, China; Southern Regional Collaborative Innovation Center for Grain and Oil Crops in China, Hunan Agricultural University, Changsha 410128, China. Electronic address:

Proteinaceous α-amylase inhibitors have specialized activities that make some strong inhibition of α-amylases. New α-amylase inhibitors continue to be discovered so far. A proteinaceous α-amylase inhibitor CL-AI was isolated and identified from chickpea seeds. CL-AI, encoded by Q9SMJ4, was a storage legumin precursor containing one α-chain and one β-chain, and each chain possessed a same conserved cupin domain. Amino acid mutation and deficiency of cupin domain would lead to loss of α-amylase inhibitory activity, indicating that it was essential for inhibitory activity. CL-AI(α + β) in its single stranded state in vivo had inhibitory activity. After it was processed into one α-chain and one β-chain, the two chains were connected to each other via disulfide bond, which would cover the cupin domains and lead to the loss of inhibitory activity. The CL-AI(α + β), α-chain and β-chain could inhibit various α-amylases and delay the seed germination of wheat, rice and maize as well as the growth and development of potato beetle larva. Two cupin proteins, Glycinin G1 in soybean and Glutelinin in rice were also found to have inhibitory activity. Our results indicated that the cupin domain is involved in α-amylase inhibitory activity and the proteins with a cupin domain may be a new kind of proteinaceous α-amylase inhibitor.
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http://dx.doi.org/10.1016/j.plantsci.2018.10.001DOI Listing
December 2018